@article {pmid39278553,
year = {2024},
author = {Miranda, MA and Tsalatsanis, A and Trotter, JR and Arnold, DE and Squire, JD and Kidd, S and Parikh, S and Marsh, RA and Griffith, LM and Mallhi, K and Chellapandian, D and Lim, SS and Grunebaum, E and Sullivan, KE and Newburger, PE and Dinauer, MC and Cowan, MJ and Dvorak, CC and Haddad, E and Kohn, DB and Notarangelo, LD and Pai, SY and Puck, JM and Pulsipher, MA and Torgerson, TR and Malech, HL and Kang, EM and Morton, FB and Leiding, JW},
title = {High symptom burden in female X-linked chronic granulomatous disease carriers.},
journal = {Clinical immunology (Orlando, Fla.)},
volume = {},
number = {},
pages = {110364},
doi = {10.1016/j.clim.2024.110364},
pmid = {39278553},
issn = {1521-7035},
}

@article {pmid39276915,
year = {2024},
author = {Haab, B and Qian, L and Staal, B and Jain, M and Fahrmann, J and Worthington, C and Prosser, D and Velokokhatnaya, L and Lopez, C and Tang, R and Hurd, MW and Natarajan, G and Kumar, S and Smith, L and Hanash, S and Batra, SK and Maitra, A and Lokshin, A and Huang, Y and Brand, RE},
title = {A Rigorous Multi-Laboratory Study of Known PDAC Biomarkers Identifies Increased Sensitivity and Specificity Over CA19-9 Alone.},
journal = {Cancer letters},
volume = {},
number = {},
pages = {217245},
doi = {10.1016/j.canlet.2024.217245},
pmid = {39276915},
issn = {1872-7980},
abstract = {A blood test that enables surveillance for early-stage pancreatic ductal adenocarcinoma (PDAC) is an urgent need. Independent laboratories have reported PDAC biomarkers that could improve biomarker performance over CA19-9 alone, but the performance of the previously reported biomarkers in combination is not known. Therefore, we conducted a coordinated case/control study across multiple laboratories using common sets of blinded training and validation samples (132 and 295 plasma samples, respectively) from PDAC patients and non-PDAC control subjects representing conditions under which surveillance occurs. We analyzed the training set to identify candidate biomarker combination panels using biomarkers across laboratories, and we applied the fixed panels to the validation set. The panels identified in the training set, CA19-9 with CA199.STRA, LRG1, TIMP-1, TGM2, THSP2, ANG, and MUC16.STRA, achieved consistent performance in the validation set. The panel of CA19-9 with the glycan biomarker CA199.STRA improved sensitivity from 0.44 with 0.98 specificity for CA19-9 alone to 0.71 with 0.98 specificity (p < 0.001, 1000-fold bootstrap). Similarly, CA19-9 combined with the protein biomarker LRG1 and CA199.STRA improved specificity from 0.16 with 0.94 sensitivity for CA19-9 to 0.65 with 0.89 sensitivity (p < 0.001, 1000-fold bootstrap). We further validated significantly improved performance using biomarker panels that did not include CA19-9. This study establishes the effectiveness of a coordinated study of previously discovered biomarkers and identified panels of those biomarkers that significantly increased the sensitivity and specificity of early-stage PDAC detection in a rigorous validation trial.},
}

@article {pmid39276235,
year = {2024},
author = {Miles, RC and Chou, SH and Lamb, LR and Narayan, A and Tran, NT and Lee, JM},
title = {Framework for Successful Integration of Health Services Research Into a Breast Imaging Career.},
journal = {Journal of breast imaging},
volume = {},
number = {},
pages = {},
doi = {10.1093/jbi/wbae042},
pmid = {39276235},
issn = {2631-6129},
abstract = {Health services research (HSR) is a multidisciplinary field of inquiry that examines how health care is structured, providing valuable data on health care outcomes and delivery. Over the past few decades, a shift in the U.S. health care system toward value-based care has placed a priority on health services topics. Health services research has been central to the evolution of breast imaging over this period, with increased emphasis placed on the following: (1) design of appropriate-use criteria for imaging services; (2) determination of cost-effectiveness of imaging protocols and screening regimens guiding policy; and (3) evaluation of policy related to reimbursement for diagnostic imaging and image-guided procedures. Examples of HSR topics that can be applied directly to breast imaging include evaluation of health care availability and accessibility, analysis of health care use patterns, exploration of patient preferences, assessment of technological innovation, development and implementation of clinical practice guidelines and screening strategies, and examination of health care organization and delivery models. Breast imaging radiologists who perform HSR are uniquely positioned to advocate for patients, to promote transformative health care interventions, and to influence policy changes and public health initiatives in breast imaging through analysis of health care data and translation of their research findings. In this Training and Professional Development article, we aim to provide practical approaches to explore interest in HSR and to describe a framework for successful integration of HSR into a breast imaging career.},
}

@article {pmid39271284,
year = {2024},
author = {Grover, S and Court, L and Amoo-Mitchual, S and Longo, J and Rodin, D and Scott, AA and Lievens, Y and Yap, ML and Abdel-Wahab, M and Lee, P and Harsdorf, E and Khader, J and Jia, X and Dosanjh, M and Elzawawy, A and Ige, T and Pomper, M and Pistenmaa, D and Hardenbergh, P and Petereit, DG and Sargent, M and Cina, K and Li, B and Anacak, Y and Mayo, C and Prattipati, S and Lasebikan, N and Rendle, K and O'Brien, D and Wendling, E and Coleman, CN},
title = {Global Workforce and Access: Demand, Education, Quality.},
journal = {Seminars in radiation oncology},
volume = {34},
number = {4},
pages = {477-493},
doi = {10.1016/j.semradonc.2024.07.003},
pmid = {39271284},
issn = {1532-9461},
mesh = {Humans ; *Health Services Accessibility ; *Radiation Oncology ; *Neoplasms/radiotherapy ; Global Health ; Developing Countries ; Healthcare Disparities ; Health Services Needs and Demand ; },
abstract = {There has long existed a substantial disparity in access to radiotherapy globally. This issue has only been exacerbated as the growing disparity of cancer incidence between high-income countries (HIC) and low and middle-income countries (LMICs) widens, with a pronounced increase in cancer cases in LMICs. Even within HICs, iniquities within local communities may lead to a lack of access to care. Due to these trends, it is imperative to find solutions to narrow global disparities. This requires the engagement of a diverse cohort of stakeholders, including working professionals, non-governmental organizations, nonprofits, professional societies, academic and training institutions, and industry. This review brings together a diverse group of experts to highlight critical areas that could help reduce the current global disparities in radiation oncology. Advancements in technology and treatment, such as artificial intelligence, brachytherapy, hypofractionation, and digital networks, in combination with implementation science and novel funding mechanisms, offer means for increasing access to care and education globally. Common themes across sections reveal how utilizing these new innovations and strengthening collaborative efforts among stakeholders can help improve access to care globally while setting the framework for the next generation of innovations.},
}

Humans
*Health Services Accessibility
*Radiation Oncology
*Neoplasms/radiotherapy
Global Health
Developing Countries
Healthcare Disparities
Health Services Needs and Demand

@article {pmid39266311,
year = {2024},
author = {Smibert, OC and Trubiano, JA and Kwong, JC and Markey, KA and Slavin, MA},
title = {Protocol for a clinically annotated biorepository of samples from Australian immune-compromised patients to investigate the host-microbiome interaction.},
journal = {BMJ open},
volume = {14},
number = {9},
pages = {e085504},
doi = {10.1136/bmjopen-2024-085504},
pmid = {39266311},
issn = {2044-6055},
mesh = {Humans ; Australia ; *Gastrointestinal Microbiome ; Host Microbial Interactions/immunology ; Biological Specimen Banks ; Prospective Studies ; Research Design ; Specimen Handling/methods ; },
abstract = {INTRODUCTION: The human gut microbiota has the potential to modulate the outcomes of several human diseases. This effect is likely to be mediated through interaction with the host immune system. This protocol details the establishment of a biorepository of clinically annotated samples, which we will use to explore correlations between the gut microbiota and the immune system of immune-compromised patients. We aim to identify microbiome-related risk factors for adverse outcomes.

METHODS AND ANALYSES: This is a protocol for the development of a biorepository of clinically annotated samples collected prospectively across three centres in Melbourne, Australia. Participants will be recruited across the following clinical streams: (1) acute leukaemia and allogeneic stem cell transplant; (2) end-stage liver disease and liver transplant; (3) patients receiving any cancer immunotherapies (eg, chimeric antigen receptor therapy); (4) deceased organ donors and (5) healthy adult controls. Participants will be asked to provide paired peripheral blood and microbiota samples (stool and saliva) at either (1) single time point for healthy controls and deceased organ donors or (2) longitudinally over multiple prespecified or event-driven time points for the remaining cohorts. Sampling of fluid from bronchoalveolar lavage and colonoscopy or biopsy of tissues undertaken during routine care will also be performed.

ETHICS AND DISSEMINATION: Ethical approval has been obtained from the relevant local ethics committee (The Royal Melbourne Hospital Human Research Ethics Committee). The results of this study will be disseminated by various scientific platforms including social media, international presentations and publication in peer-reviewed journals.

TRIAL REGISTRATION NUMBER: ACTRN12623001105639. Date registered 20 October 2023.},
}

Humans
Australia
*Gastrointestinal Microbiome
Host Microbial Interactions/immunology
Biological Specimen Banks
Prospective Studies
Research Design
Specimen Handling/methods

@article {pmid39266299,
year = {2024},
author = {Park, SH and Tsuzuki, S and Contino, KF and Ollodart, J and Eber, MR and Yu, Y and Steele, LR and Inaba, H and Kamata, Y and Kimura, T and Coleman, I and Nelson, PS and Muñoz-Islas, E and Jiménez-Andrade, JM and Martin, TJ and Mackenzie, KD and Stratton, JR and Hsu, FC and Peters, CM and Shiozawa, Y},
title = {Crosstalk between bone metastatic cancer cells and sensory nerves in bone metastatic progression.},
journal = {Life science alliance},
volume = {7},
number = {12},
pages = {},
doi = {10.26508/lsa.202302041},
pmid = {39266299},
issn = {2575-1077},
mesh = {Animals ; *Bone Neoplasms/secondary/metabolism ; Humans ; Mice ; *Calcitonin Gene-Related Peptide/metabolism ; *Disease Progression ; *Sensory Receptor Cells/metabolism ; *Cell Proliferation ; Cell Line, Tumor ; Calcitonin Receptor-Like Protein/metabolism/genetics ; Female ; Male ; Signal Transduction ; },
abstract = {Although the role of peripheral nerves in cancer progression has been appreciated, little is known regarding cancer/sensory nerve crosstalk and its contribution to bone metastasis and associated pain. In this study, we revealed that the cancer/sensory nerve crosstalk plays a crucial role in bone metastatic progression. We found that (i) periosteal sensory nerves expressing calcitonin gene-related peptide (CGRP) are enriched in mice with bone metastasis; (ii) cancer patients with bone metastasis have elevated CGRP serum levels; (iii) bone metastatic patient tumor samples express elevated calcitonin receptor-like receptor (CRLR, a CGRP receptor component); (iv) higher CRLR levels in cancer patients are negatively correlated with recurrence-free survival; (v) CGRP induces cancer cell proliferation through the CRLR/p38/HSP27 pathway; and (vi) blocking sensory neuron-derived CGRP reduces cancer cell proliferation in vitro and bone metastatic progression in vivo. This suggests that CGRP-expressing sensory nerves are involved in bone metastatic progression and that the CGRP/CRLR axis may serve as a potential therapeutic target for bone metastasis.},
}

Animals
*Bone Neoplasms/secondary/metabolism
Humans
Mice
*Calcitonin Gene-Related Peptide/metabolism
*Disease Progression
*Sensory Receptor Cells/metabolism
*Cell Proliferation
Cell Line, Tumor
Calcitonin Receptor-Like Protein/metabolism/genetics
Female
Male
Signal Transduction

@article {pmid39265260,
year = {2024},
author = {Bakaloudi, DR and Koehne, EL and Diamantopoulos, LN and Holt, SK and Sekar, RR and Ghali, F and Vakar-Lopez, F and Nyame, YA and Psutka, SP and Gore, JL and de la Calle, CM and Lin, DW and Schade, GR and Liao, JJ and Hsieh, AC and Yezefski, T and Hawley, JE and Yu, EY and Montgomery, RB and Grivas, P and Wright, JL},
title = {Small Cell Bladder Cancer: Treatment Patterns for Local Disease and Associated Outcomes. A Retrospective Cohort Study.},
journal = {Clinical genitourinary cancer},
volume = {22},
number = {6},
pages = {102208},
doi = {10.1016/j.clgc.2024.102208},
pmid = {39265260},
issn = {1938-0682},
abstract = {BACKGROUND: Small cell bladder cancer (SCBC) is a rare histologic subtype with relative paucity of data regarding treatment response and outcomes. We reviewed 2 databases to compare outcomes in patients with localized SCBC treated with cystectomy versus concurrent chemoradiotherapy (CCRT). We hypothesized that survival would be similar with these therapy approaches.

METHODS: We retrospectively reviewed our institutional and SEER-Medicare databases to identify patients with SCBC. Overall survival (OS) was determined from the date of diagnosis to last follow-up/death. For those with nonmetastatic disease, a multivariate Cox analysis was used to compare locoregional therapy with neoadjuvant chemotherapy (NAC) + cystectomy versus CCRT.

RESULTS: We identified 53 patients in our institutional database and 1166 patients in SEER-Medicare with localized SCBC. Median OS (mOS) with NAC + cystectomy was 46 months (95% CI, 21-72) and 45 months (95% CI, 0-104) in the institutional and SEER-Medicare databases, respectively, whereas mOS with CCRT was 26 months (95% CI, 5-47) and 23 months (95% CI, 18-28) in the 2 series, respectively. In multivariate analysis, NAC followed by cystectomy was associated with an approximately 30% reduction in mortality compared to CCRT in both institutional and national databases but did not reach statistical significance (Institution HR 0.71, 95% CI, 0.22-2.4, P = .58; SEER HR 0.73, 95% CI, 0.49-1.08; P = .11).

CONCLUSIONS: SCBC is very aggressive with limited survival observed in our institutional and SEER-Medicare datasets regardless of locoregional therapy used. There is an unmet need to define the optimal locoregional therapy for nonmetastatic stage and identify novel therapeutic targets.},
}

@article {pmid39264595,
year = {2024},
author = {Robbins, HA and Feng, X and Etzioni, R},
title = {Cancer Stage vs Mortality End Points in Randomized Clinical Trials of Cancer Screening.},
journal = {JAMA},
volume = {},
number = {},
pages = {},
doi = {10.1001/jama.2024.16365},
pmid = {39264595},
issn = {1538-3598},
}

@article {pmid39264541,
year = {2024},
author = {Ratnayake, A and Hernandez, JH and Justman, J and Farley, JE and Hirsch-Moverman, Y and Ho, K and Mayer, S and Oluyomi, A and Sobieszczyk, ME and Swaminathan, S and Skalland, T and Tapsoba, JD and , and Kissinger, PJ},
title = {Vaccine Hesitancy at Nine Community Sites Across the United States, Early in COVID-19 Vaccine Rollout.},
journal = {Journal of racial and ethnic health disparities},
volume = {},
number = {},
pages = {},
pmid = {39264541},
issn = {2196-8837},
support = {UM1AI068619//Division of Intramural Research, National Institute of Allergy and Infectious Diseases/ ; },
abstract = {BACKGROUND: Vaccine hesitancy has been a significant concern throughout the COVID-19 pandemic. Vaccine hesitancy can be attributed to lack of confidence in vaccines, complacency about the health threat, or lack of convenience of vaccination. To date, few studies have used methods designed to include populations underrepresented in research when identifying factors associated with vaccine hesitancy.

METHODS: Between January and July 2021, potential participants were recruited from community venues selected through time-location sampling in 15 defined communities in the United States. Study staff administered a questionnaire on demographics, COVID-19 behaviors and attitudes, and vaccination status or intention to consenting individuals. Vaccine hesitancy was analyzed among those age 18 years and older from nine of the 15 sites and was defined as self-reported neutral, unlikely, or very unlikely vaccine intention. Logistic regression modeling, adjusted for site, identified factors associated with vaccine hesitancy.

RESULTS: Among 11,559 individuals, vaccine hesitancy by site ranged from 8.7 to 31.1%. Vaccine hesitancy was associated with being Black compared to White, being White compared to Asian, younger age, unstable housing, being unemployed, lower income, having a disability, providing care in home, not reporting inability to visit sick or elderly relatives during the pandemic, not reporting increased anxiety during the pandemic, and not spending more time with loved ones during the pandemic.

CONCLUSIONS: In these selected US communities, early in vaccine rollout, there were significant racial disparities in vaccine hesitancy. Additionally, individuals who were more marginalized due to their socioeconomic status were more likely to report vaccine hesitancy. Vaccine campaigns should make efforts to remove barriers to vaccination, by improving convenience.},
}

@article {pmid39229031,
year = {2024},
author = {Bhattacharya, T and Alleman, EM and Noyola, AC and Emerman, M and Malik, HS},
title = {A conserved opal termination codon optimizes a temperature-dependent tradeoff between protein production and processing in alphaviruses.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {39229031},
issn = {2692-8205},
support = {U54 AI170792/AI/NIAID NIH HHS/United States ; },
abstract = {Alphaviruses are enveloped, single-stranded, positive-sense RNA viruses that often require transmission between arthropod and vertebrate hosts for their sustained propagation. Most alphaviruses encode an opal (UGA) termination codon in nonstructural protein 3 (nsP3) upstream of the viral polymerase, nsP4. The selective constraints underlying the conservation of the opal codon are poorly understood. Using primate and mosquito cells, we explored the role and selective pressure on the nsP3 opal codon through extensive mutational analysis in the prototype alphavirus, Sindbis virus (SINV). We found that the opal codon is highly favored over all other codons in primate cells under native 37°C growth conditions. However, this preference is diminished in mosquito and primate cells grown at a lower temperature. Thus, the primary determinant driving the selection of the opal stop codon is not host genetics but the passaging temperature. We show that the opal codon is preferred over amber and ochre termination codons because it results in the highest translational readthrough and polymerase production. However, substituting the opal codon with sense codons leads to excessive full-length polyprotein (P1234) production, which disrupts optimal nsP polyprotein processing, delays the switch from minus-strand to positive-strand RNA production, and significantly reduces SINV fitness at 37°C; this fitness defect is relieved at lower temperatures. A naturally occurring suppressor mutation unexpectedly compensates for a delayed transition from minus to genomic RNA production by also delaying the subsequent transition between genomic and sub-genomic RNA production. Our study reveals that the opal stop codon is the best solution for alphavirus replication at 37°C, producing enough nsP4 protein to maximize replication without disrupting nsP processing and RNA replication transitions needed for optimal fitness. Our study uncovers the intricate strategy dual-host alphaviruses use at a single codon to optimize fitness.},
}

@article {pmid39261482,
year = {2024},
author = {Zhang, B and Fong, Y and Fintzi, J and Chu, E and Janes, HE and Kenny, A and Carone, M and Benkeser, D and van der Laan, LWP and Deng, W and Zhou, H and Wang, X and Lu, Y and Yu, C and Borate, B and Chen, H and Reeder, I and Carpp, LN and Houchens, CR and Martins, K and Jayashankar, L and Huynh, C and Fichtenbaum, CJ and Kalams, S and Gay, CL and Andrasik, MP and Kublin, JG and Corey, L and Neuzil, KM and Priddy, F and Das, R and Girard, B and El Sahly, HM and Baden, LR and Jones, T and Donis, RO and Koup, RA and Gilbert, PB and Follmann, D and , and , and , and , },
title = {Omicron COVID-19 immune correlates analysis of a third dose of mRNA-1273 in the COVE trial.},
journal = {Nature communications},
volume = {15},
number = {1},
pages = {7954},
pmid = {39261482},
issn = {2041-1723},
mesh = {Humans ; *COVID-19/immunology/virology/prevention & control ; *SARS-CoV-2/immunology ; *Antibodies, Neutralizing/immunology ; *Antibodies, Viral/immunology/blood ; *Spike Glycoprotein, Coronavirus/immunology ; *Immunization, Secondary ; *2019-nCoV Vaccine mRNA-1273/administration & dosage/immunology ; COVID-19 Vaccines/immunology/administration & dosage ; Female ; Male ; Adult ; Vaccine Efficacy ; },
abstract = {In the phase 3 Coronavirus Efficacy (COVE) trial (NCT04470427), post-dose two Ancestral Spike-specific binding (bAb) and neutralizing (nAb) antibodies were shown to be correlates of risk (CoR) and of protection against Ancestral-lineage COVID-19 in SARS-CoV-2 naive participants. In the SARS-CoV-2 Omicron era, Omicron subvariants with varying degrees of immune escape now dominate, seropositivity rates are high, and booster doses are administered, raising questions on whether and how these developments affect the bAb and nAb correlates. To address these questions, we assess post-boost BA.1 Spike-specific bAbs and nAbs as CoRs and as correlates of booster efficacy in COVE. For naive individuals, bAbs and nAbs inversely correlate with Omicron COVID-19: hazard ratios (HR) per 10-fold marker increase (95% confidence interval) are 0.16 (0.03, 0.79) and 0.31 (0.10, 0.96), respectively. In non-naive individuals the analogous results are similar: 0.15 (0.04, 0.63) and 0.28 (0.07, 1.08). For naive individuals, three vs two-dose booster efficacy correlates with predicted nAb titer at exposure, with estimates -8% (-126%, 48%), 50% (25%, 67%), and 74% (49%, 87%), at 56, 251, and 891 Arbitrary Units/ml. These results support the continued use of antibody as a surrogate endpoint.},
}

Humans
*COVID-19/immunology/virology/prevention & control
*SARS-CoV-2/immunology
*Antibodies, Neutralizing/immunology
*Antibodies, Viral/immunology/blood
*Spike Glycoprotein, Coronavirus/immunology
*Immunization, Secondary
*2019-nCoV Vaccine mRNA-1273/administration & dosage/immunology
COVID-19 Vaccines/immunology/administration & dosage
Female
Male
Adult
Vaccine Efficacy

@article {pmid39260945,
year = {2024},
author = {Barta, JA and Mazzone, PJ and Nair, VS},
title = {Multi-Cancer and Single-Cancer Early Detection Testing: Opportunities and Challenges.},
journal = {Chest},
volume = {166},
number = {3},
pages = {425-428},
doi = {10.1016/j.chest.2024.03.044},
pmid = {39260945},
issn = {1931-3543},
mesh = {Humans ; *Early Detection of Cancer/methods ; *Neoplasms/diagnosis ; Mass Screening/methods ; },
}

Humans
*Early Detection of Cancer/methods
*Neoplasms/diagnosis
Mass Screening/methods

@article {pmid39260570,
year = {2024},
author = {Kongtim, P and Vittayawacharin, P and Zou, J and Srour, S and Shaffer, B and Shapiro, RM and Varma, A and McGuirk, J and Dholaria, BR and McCurdy, SR and DeZern, AE and Bejanyan, N and Bashey, A and Furst, S and Castagna, L and Mariotti, J and Ruggeri, A and Bailen, R and Teshima, T and Xiao-Jun, H and Bonfim, C and Aung, F and Cao, K and Carpenter, PA and Hamadani, M and Askar, M and Fernandez-Vina, M and Girnita, A and Ciurea, SO},
title = {ASTCT Consensus Recommendations on Testing and Treatment of Patients with Donor-specific Anti-HLA Antibodies.},
journal = {Transplantation and cellular therapy},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jtct.2024.09.005},
pmid = {39260570},
issn = {2666-6367},
abstract = {Donor-specific anti-HLA antibodies (DSA) are an important cause of engraftment failure and may negatively impact survival outcomes of patients receiving allogeneic hematopoietic stem cell transplantation (HSCT) using an HLA-mismatched allograft. The incidence of DSA varies across studies, depending on individual factors, detection or identification methods and thresholds considered clinically relevant. Although DSA testing by multiplex bead arrays remains semiquantitative, it has been widely adopted as a standard test in most transplant centers. Additional testing to determine risk of allograft rejection may include assays with HLA antigens in natural conformation, such as flow cytometric crossmatch, and/or antibody binding assays, such as C1q testing. Patients with low level of DSA (<2,000 mean fluorescence intensity; MFI) may not require treatment, while others with very high level of DSA (>20,000 MFI) may be at very high-risk for engraftment failure despite current therapies. By contrast, in patients with moderate or high level of DSA, desensitization therapy can successfully mitigate DSA levels and improve donor cell engraftment rate, with comparable outcomes to patients without DSA. Treatment is largely empirical and multimodal, involving the removal, neutralization, and blocking of antibodies, as well as inhibition of antibody production to prevent activation of the complement cascade. Desensitization protocols are based on accumulated multicenter experience, while prospective multicenter studies remain lacking. Most patients require a full intensity protocol that includes plasma exchange, while protocols relying only on rituximab and intravenous immunoglobulin may be sufficient for patients with lower DSA levels and negative C1q and/or flow cytometric crossmatch. Monitoring DSA levels before and after HSCT could guide preemptive treatment when high levels persist after stem cell infusion. This paper aims to standardize current evidence-based practice and formulate future directions to improve upon current knowledge and advance treatment for this relatively rare, but potentially serious complication in allogeneic HSCT recipients.},
}

@article {pmid39259414,
year = {2024},
author = {Nuechterlein, N and Cimino, S and Shelbourn, A and Ha, V and Arora, S and Rajan, S and Shapiro, LG and Holland, EC and Aldape, K and McGranahan, T and Gilbert, MR and Cimino, PJ},
title = {HOXD12 defines an age-related aggressive subtype of oligodendroglioma.},
journal = {Acta neuropathologica},
volume = {148},
number = {1},
pages = {41},
pmid = {39259414},
issn = {1432-0533},
support = {DGE-1762114//National Science Foundation Graduate Research Fellowship Program/ ; Intramural Research Program/NS/NINDS NIH HHS/United States ; },
mesh = {Humans ; *Oligodendroglioma/genetics/pathology ; *Homeodomain Proteins/genetics/metabolism ; *Brain Neoplasms/genetics/pathology/metabolism ; Middle Aged ; Male ; Female ; Adult ; Transcription Factors/genetics/metabolism ; DNA Methylation ; Aged ; Age Factors ; Mutation ; },
abstract = {Oligodendroglioma, IDH-mutant and 1p/19q-codeleted has highly variable outcomes that are strongly influenced by patient age. The distribution of oligodendroglioma age is non-Gaussian and reportedly bimodal, which motivated our investigation of age-associated molecular alterations that may drive poorer outcomes. We found that elevated HOXD12 expression was associated with both older patient age and shorter survival in the TCGA (FDR < 0.01, FDR = 1e-5) and the CGGA (p = 0.03, p < 1e-3). HOXD12 gene body hypermethylation was associated with older age, higher WHO grade, and shorter survival in the TCGA (p < 1e-6, p < 0.001, p < 1e-3) and with older age and higher WHO grade in Capper et al. (p < 0.002, p = 0.014). In the TCGA, HOXD12 gene body hypermethylation and elevated expression were independently prognostic of NOTCH1 and PIK3CA mutations, loss of 15q, MYC activation, and standard histopathological features. Single-nucleus RNA and ATAC sequencing data showed that HOXD12 activity was elevated in neoplastic tissue, particularly within cycling and OPC-like cells, and was associated with a stem-like phenotype. A pan-HOX DNA methylation analysis revealed an age and survival-associated HOX-high signature that was tightly associated with HOXD12 gene body methylation. Overall, HOXD12 expression and gene body hypermethylation were associated with an older, atypically aggressive subtype of oligodendroglioma.},
}

Humans
*Oligodendroglioma/genetics/pathology
*Homeodomain Proteins/genetics/metabolism
*Brain Neoplasms/genetics/pathology/metabolism
Middle Aged
Male
Female
Adult
Transcription Factors/genetics/metabolism
DNA Methylation
Aged
Age Factors
Mutation

@article {pmid39259185,
year = {2024},
author = {Kalia, SS and Boddicker, NJ and Yadav, S and Huang, H and Na, J and Hu, C and Ambrosone, CB and Yao, S and Haiman, CA and Chen, F and John, EM and Kurian, AW and Guo, B and Lindström, S and Auer, P and Lacey, JV and Neuhausen, SL and Martinez, ME and Sandler, DP and O'Brien, KM and Taylor, JA and Teras, LR and Hodge, JM and Lori, A and Bodelon, C and Trentham-Dietz, A and Burnside, ES and Vachon, CM and Winham, SJ and Goldgar, DE and Domchek, SM and Nathanson, KL and Weitzel, JN and Couch, FJ and Kraft, P},
title = {Development of a breast cancer risk prediction model integrating monogenic, polygenic, and epidemiologic risk.},
journal = {Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology},
volume = {},
number = {},
pages = {},
doi = {10.1158/1055-9965.EPI-24-0594},
pmid = {39259185},
issn = {1538-7755},
abstract = {BACKGROUND: Breast cancer has been associated with monogenic, polygenic, and epidemiologic (clinical, reproductive and lifestyle) risk factors, but studies evaluating the combined effects of these factors have been limited.

METHODS: We extended previous work in breast cancer risk modeling, incorporating pathogenic variants (PV) in six breast cancer predisposition genes and a 105-SNP polygenic risk score (PRS), to include an epidemiologic risk score (ERS) in a sample of non-Hispanic White women drawn from prospective cohorts and population-based case-control studies, with 23,518 cases and 22,832 controls, from the Cancer Risk Estimates Related to Susceptibility (CARRIERS) Consortium.

RESULTS: The model predicts 4.4-fold higher risk of breast cancer for postmenopausal women with no predisposition PV and median PRS, but with the highest versus lowest ERS. Overall, women with CHEK2 PVs had >20% lifetime risk of breast cancer. However, 15.6% of women with CHEK2 PVs and a family history of breast cancer, and 45.1% of women with CHEK2 PVs but without a family history of breast cancer, had low (<20%) predicted lifetime risk and thus were below the threshold for MRI screening. CHEK2 PV carriers at the 10th percentile of the joint distribution of ERS and PRS, without a family history of breast cancer, had a predicted lifetime risk similar to the general population.

CONCLUSIONS: These results illustrate that an ERS, alone and combined with the PRS, can contribute to clinically relevant risk stratification.

IMPACT: Integrating monogenic, polygenic, and epidemiologic risk factors in breast cancer risk prediction models may inform personalized screening and prevention efforts.},
}

@article {pmid39258792,
year = {2024},
author = {Anderson, AC and Ho, J and Hall, ET and Hannan, R and Liao, JJ and Louie, AV and Ma, TM and Psutka, SP and Rengan, R and Siva, S and Swaminath, A and Tachiki, L and Tang, C and Teh, BS and Tsai, J and Tykodi, SS and Weg, E and Zaorsky, NG and Lo, SS},
title = {Focal therapy for oligometastatic and oligoprogressive renal cell carcinoma: a narrative review.},
journal = {Future oncology (London, England)},
volume = {},
number = {},
pages = {1-16},
doi = {10.1080/14796694.2024.2389769},
pmid = {39258792},
issn = {1744-8301},
abstract = {Metastatic renal cell carcinoma (RCC) can present with oligometastatic disease and/or develop oligoprogression following systemic therapy. Cytoreductive and focal metastasis-directed therapy options include resection, stereotactic ablative radiation and thermal ablation. Aggressive focal therapy may allow delay in initiation of or modification to systemic therapy and improve clinical outcomes. In this narrative review we synthesize current practice guidelines and prospective data on focal therapy management options and highlight future research. Patient selection and the choice of focal treatment techniques are controversial due to limited and heterogeneous data and patients may benefit from multidisciplinary evaluation. Prospective comparative trials with clearly defined inclusion criteria and relevant end points are needed to clarify the risks and benefits of different approaches.},
}

@article {pmid39255537,
year = {2024},
author = {Triner, D and Graf, RP and Madison, RW and Gjoerup, O and Tukachinsky, H and Ross, JS and Quintanilha, JCF and Li, G and Cheng, HH and Pritchard, CC and Zurita, AJ and Qin, Q and Zhang, T and Agarwal, N and Reichert, ZR and Mateo, J and Cieslik, M and Morgan, TM},
title = {Durable benefit from poly(ADP-ribose) polymerase inhibitors in metastatic prostate cancer in routine practice: biomarker associations and implications for optimal clinical next-generation sequencing testing.},
journal = {ESMO open},
volume = {9},
number = {9},
pages = {103684},
doi = {10.1016/j.esmoop.2024.103684},
pmid = {39255537},
issn = {2059-7029},
abstract = {BACKGROUND: Controlled trials have consistently demonstrated the efficacy of poly(ADP-ribose) polymerase inhibitors (PARPis) in patients with metastatic castration-resistant prostate cancer (mCRPC) and BRCA1 or BRCA2 alterations (BRCAalt). However, the reported efficacy of PARPi for alterations in other homologous recombination repair (HRR) genes is less consistent. We sought to evaluate the routine practice effectiveness of PARPi between and within these groups.

DESIGN: Patient-level data from a deidentified nationwide (USA-based) cancer clinico-genomic database between January 2011 and September 2023 were extracted. Patients with mCRPC and comprehensive genomic profiling by liquid biopsy [circulating tumor DNA (ctDNA)] or tissue (tumor) biopsy and who received single-agent PARPi were included and grouped by BRCAalt, ATMalt, other HRR, or no HRR. We further subcategorized BRCAalt into homozygous loss (BRCAloss) and all other deleterious BRCAalt (otherBRCAalt).

RESULTS: A total of 445 patients met inclusion criteria: 214 with tumor and 231 with ctDNA. BRCAalt had more favorable outcomes to PARPi compared with ATM, other HRR, and no HRR groups. Within the BRCAalt subgroup, compared with other BRCAalt, BRCAloss had a more favorable time to next treatment (median 9 versus 19.4 months, P = 0.005), time to treatment discontinuation (median 8 versus 14 months, P = 0.006), and routine practice overall survival (median 14.7 versus 19.4 months, P = 0.016). Tumor BRCAloss prevalence (3.1%) was similar to ctDNA prevalence in liquid biopsy specimens with high tumor fraction (>20%). BRCAloss was not detected in orthogonal germline testing.

CONCLUSIONS: PARPi routine practice effectiveness between groups mirrors prospective trials. Within the BRCAalt group, BRCAloss had the best outcomes. Unless the ctDNA tumor fraction is very high, somatic tissue testing (archival or metastatic) should be prioritized to identify patients who may benefit most from PARPi. When tissue testing is not clinically feasible, sufficient ctDNA tumor fraction levels for detection are enriched at clinical timepoints associated with tumor progression.},
}

@article {pmid39255440,
year = {2024},
author = {Barata, P and Tangen, C and Plets, M and Thompson, IM and Narayan, V and George, DJ and Heng, DYC and Shuch, B and Stein, M and Gulati, S and Tretiakova, M and Tripathi, A and Bjarnason, GA and Humphrey, P and Adeniran, A and Vaishampayan, U and Alva, A and Zhang, T and Cole, S and Lara, PN and Lerner, SP and Balzer-Haas, N and Pal, SK},
title = {Final Overall Survival Analysis of S1500: A Randomized, Phase II Study Comparing Sunitinib With Cabozantinib, Crizotinib, and Savolitinib in Advanced Papillary Renal Cell Carcinoma.},
journal = {Journal of clinical oncology : official journal of the American Society of Clinical Oncology},
volume = {},
number = {},
pages = {JCO2400767},
doi = {10.1200/JCO.24.00767},
pmid = {39255440},
issn = {1527-7755},
abstract = {Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.Mesenchymal-epithelial transition (MET) signaling pathway plays a role in the pathogenesis of selected patients with papillary renal cell carcinoma (PRCC). In the phase II PAPMET trial (ClinicalTrials.gov identifier: NCT02761057), cabozantinib significantly prolonged progression-free survival and improved objective response rate compared with sunitinib in patients with advanced PRCC. Here, we present the final overall survival (OS) analysis. In this multicenter, randomized phase II, open-label trial, 147 patients with advanced PRCC who have received up to one previous therapy (excluding vascular endothelial growth factor-directed agents) were assigned to sunitinib, cabozantinib, crizotinib, or savolitinib. Ultimately, savolitinib and crizotinib arms were closed because of futility. With a median follow-up of 17.5 months, the median OS was 21.5 months (95% CI, 12.0 to 28.1) with cabozantinib and 17.3 months (95% CI, 12.8 to 21.8) with sunitinib (hazard ratio, 0.83; 95% CI, 0.51 to 1.36; P = .46). The OS landmark estimates for cabozantinib and sunitinib were 50% versus 39% at 24 months and 32% versus 28% at 36 months. In conclusion, we observed no significant difference in OS across treatment arms. Although cabozantinib represents a well-supported option for advanced PRCC, the lack of survival benefit underscores the need to develop novel therapies for this disease.},
}

@article {pmid39255368,
year = {2024},
author = {Li, W and Li, R and Feng, Z and Ning, J and , },
title = {Dynamic and concordance-assisted learning for risk stratification with application to Alzheimer's disease.},
journal = {Biostatistics (Oxford, England)},
volume = {},
number = {},
pages = {},
doi = {10.1093/biostatistics/kxae036},
pmid = {39255368},
issn = {1468-4357},
support = {R01CA269696/NH/NIH HHS/United States ; },
abstract = {Dynamic prediction models capable of retaining accuracy by evolving over time could play a significant role for monitoring disease progression in clinical practice. In biomedical studies with long-term follow up, participants are often monitored through periodic clinical visits with repeat measurements until an occurrence of the event of interest (e.g. disease onset) or the study end. Acknowledging the dynamic nature of disease risk and clinical information contained in the longitudinal markers, we propose an innovative concordance-assisted learning algorithm to derive a real-time risk stratification score. The proposed approach bypasses the need to fit regression models, such as joint models of the longitudinal markers and time-to-event outcome, and hence enjoys the desirable property of model robustness. Simulation studies confirmed that the proposed method has satisfactory performance in dynamically monitoring the risk of developing disease and differentiating high-risk and low-risk population over time. We apply the proposed method to the Alzheimer's Disease Neuroimaging Initiative data and develop a dynamic risk score of Alzheimer's Disease for patients with mild cognitive impairment using multiple longitudinal markers and baseline prognostic factors.},
}

@article {pmid39255259,
year = {2024},
author = {Iwu, CD and Cox, SN and Sohlberg, SL and Kim, AE and Logue, J and Han, PD and Sibley, TR and Ilcisin, M and Fay, KA and Lee, J and McCulloch, DJ and Wang, Y and Boeckh, M and Englund, JA and Starita, LM and Hajat, A and Chu, HY},
title = {"I probably shouldn't go in today": Inequitable access to paid sick leave and its impacts on health behaviors during the emergence of COVID-19 in the Seattle area.},
journal = {PloS one},
volume = {19},
number = {9},
pages = {e0307734},
doi = {10.1371/journal.pone.0307734},
pmid = {39255259},
issn = {1932-6203},
mesh = {Humans ; *COVID-19/epidemiology ; Female ; Male ; Adult ; *Sick Leave/statistics & numerical data/economics ; Middle Aged ; Washington/epidemiology ; Health Behavior ; SARS-CoV-2 ; Socioeconomic Factors ; Income ; Young Adult ; Surveys and Questionnaires ; Adolescent ; },
abstract = {This study examines inequities in access to paid sick leave (PSL) by race/ethnicity, income, and sex and the role of PSL access on leave-taking and care-seeking behaviors among Seattle-area workers in the months leading up to and during the emergence of COVID-19 in the region. Survey responses were collected online and in-person from individuals experiencing acute respiratory illness symptoms between November 2019 and March 2020 as part of a community-based respiratory viral surveillance study. Chi-square tests and log-binomial models were used to assess the association between PSL access and various socioeconomic indicators. A total of 66.6% (n = 2,276) respondents reported access to PSL. Proportionally, access to PSL was highest in respondents identifying as Asian (70.5%), followed by White (68.7%), Latine (58.4%), Multiracial (57.1%), Black (47.1%), and Other (43.1%). Access to PSL increased with household income. Eighty three percent of high-income respondents reported access compared to 52.9% of low-income households. Only 23.3% of the lowest-income households reported access to PSL. Fewer females (65.2%) than males (70.7%) reported access to PSL. Access to PSL is inequitably distributed across income, race/ethnicity, and sex. This study reinforces the vast body of knowledge on how socioeconomic inequalities increase individual and community-level vulnerability to the impacts of infectious disease outbreaks. It also supports the role of labor and economic policy in mitigating (or exacerbating) these impacts. Exemplified by the COVID-19 pandemic, universal access to PSL, especially for marginalized populations, benefits all.},
}

Humans
*COVID-19/epidemiology
Female
Male
Adult
*Sick Leave/statistics & numerical data/economics
Middle Aged
Washington/epidemiology
Health Behavior
SARS-CoV-2
Socioeconomic Factors
Income
Young Adult
Surveys and Questionnaires
Adolescent

@article {pmid39255401,
year = {2022},
author = {Malik, HS},
title = {Driving lessons: a brief (personal) history of centromere drive.},
journal = {Genetics},
volume = {222},
number = {4},
pages = {},
doi = {10.1093/genetics/iyac155},
pmid = {39255401},
issn = {1943-2631},
support = {R01-GM074108//Howard Hughes Medical Institution/ ; /NH/NIH HHS/United States ; },
}

@article {pmid39253895,
year = {2024},
author = {Naresh, KN},
title = {Understanding splenic B-cell lymphoma/leukaemia with prominent nucleoli: Diagnosis, underpinnings for disease classification and future directions.},
journal = {British journal of haematology},
volume = {},
number = {},
pages = {},
doi = {10.1111/bjh.19754},
pmid = {39253895},
issn = {1365-2141},
abstract = {The 5th edition of the WHO classification of haematolymphoid tumours (WHO-HAEM5) introduced a new category, splenic B-cell lymphoma/leukaemia with prominent nucleoli (SBLPN). The diagnostic entity B-cell prolymphocytic leukaemia (B-PLL) has been discontinued and the category of hairy cell leukaemia variant (HCLv) has been conceptually reframed. B-PLL and HCLv diagnoses were uncommon. Overlap existed between B-PLL and other indolent lymphomas like chronic lymphocytic leukaemia/small lymphocytic lymphoma (CLL/SLL). HCLv lacked consistent cytomorphological, immunophenotypic and genetic features. To address these issues, the WHO-HAEM5 classification has introduced SBLPN to serve as a temporary holding ground for entities that do not neatly fit into the existing classification. Cases previously classified as CD5-negative B-PLL and HCLv fall under the SBLPN category. Some splenic marginal zone lymphoma and splenic diffuse red pulp small B-cell lymphoma cases with higher number of medium or large nucleolated B cells would also be classified as SBLPN under the WHO-HAEM5. This review explores the rationale for discontinuing B-PLL and HCLv diagnoses. It then examines the concept of SBLPN, offers practical guidance for diagnosis and discusses future directions in classifying splenic B-cell lymphomas.},
}

@article {pmid39253833,
year = {2024},
author = {Kaplan, RC and Chan, KCG},
title = {Unequal Management and Outcomes Among Asian American Patients With Coronary Heart Disease.},
journal = {Circulation. Cardiovascular quality and outcomes},
volume = {},
number = {},
pages = {e011440},
doi = {10.1161/CIRCOUTCOMES.124.011440},
pmid = {39253833},
issn = {1941-7705},
}

@article {pmid39251835,
year = {2024},
author = {Vo, P and Srinivasan, R and Purev, E and McDuffee, E and Worthy, T and Shalabi, R and Wood, K and Wells, B and Reger, R and Stroncek, D and Geller, N and Aue, G and Tian, X and Childs, R},
title = {Durable remission of refractory and advanced stage mycosis fungoides/sezary syndrome utilizing an "outpatient" alemtuzumab, fludarabine-based reduced intensity allogeneic hematopoietic cell transplantation.},
journal = {Bone marrow transplantation},
volume = {},
number = {},
pages = {},
pmid = {39251835},
issn = {1476-5365},
}

@article {pmid39251462,
year = {2024},
author = {Ronsley, R and Bertrand, KC and Song, EZ and Timpanaro, A and Choe, M and Tlais, D and Vitanza, NA and Park, JR},
title = {CAR T cell therapy for pediatric central nervous system tumors: a review of the literature and current North American trials.},
journal = {Cancer metastasis reviews},
volume = {},
number = {},
pages = {},
pmid = {39251462},
issn = {1573-7233},
abstract = {Central nervous system (CNS) tumors are the leading cause of cancer-related death in children. Typical therapy for CNS tumors in children involves a combination of surgery, radiation, and chemotherapy. While upfront therapy is effective for many high-grade tumors, therapy at the time of relapse remains limited. Furthermore, for diffuse intrinsic pontine glioma (DIPG) and diffuse midline glioma (DMG), there are currently no curative therapies. Chimeric antigen receptor T (CAR T) cell therapy is a promising novel treatment avenue for these tumors. Here, we review the preclinical evidence for CAR T cell use in pediatric brain tumors, the preliminary clinical experience of CNS CAR T cell trials, toxicity associated with systemic and locoregional CAR T cell therapy for CNS tumors, challenges in disease response evaluation with CAR T cell therapy, and the knowledge gained from correlative biologic studies from these trials in the pediatric and young adult population.},
}

@article {pmid39248500,
year = {2024},
author = {Srinivasan, S and Richardson, BA and Wallis, JM and Fiedler, TL and Strenk, SM and Hoffman, NG and Proll, S and Chirenje, ZM and Livant, EW and Fredricks, DN and Hillier, SL and Marrazzo, JM},
title = {Vaginal Bacteria and Proinflammatory Host Immune Mediators as Biomarkers of Human Immunodeficiency Virus Acquisition Risk Among African Women.},
journal = {The Journal of infectious diseases},
volume = {},
number = {},
pages = {},
doi = {10.1093/infdis/jiae406},
pmid = {39248500},
issn = {1537-6613},
support = {NCT00705679//VOICE study/ ; UM1AI068633, UM1AI068615, UM1AI106707//National Institute of Allergy and Infectious Diseases/ ; //National Institute of Child Health and Human Development/ ; /MH/NIMH NIH HHS/United States ; /NH/NIH HHS/United States ; P30AI027757//University of Washington's Center for AIDS Research/ ; },
abstract = {BACKGROUND: Few investigations have assessed contributions of both vaginal bacteria and proinflammatory immune mediators to human immunodeficiency virus (HIV) acquisition risk in a prospective cohort.

METHODS: We conducted a nested case-control study of African women who participated in a randomized placebo-controlled trial of daily oral versus vaginal tenofovir-based preexposure prophylaxis for HIV infection. Vaginal concentrations of 23 bacterial taxa and 16 immune mediators were measured. Relationships between individual bacterial concentrations or immune mediators and HIV risk were analyzed using generalized estimating equations in a multivariable model. Factor analysis assessed relationships between combinations of bacterial taxa, immune mediators, and HIV acquisition risk.

RESULTS: We identified 177 HIV pre-seroconversion visits from 150 women who acquired HIV and 531 visits from 436 women who remained HIV uninfected. Fourteen bacterial taxa and 6 proinflammatory cytokines and chemokines were individually associated with greater HIV risk after adjusting for confounders. Women with all 14 taxa versus <14 taxa (adjusted odds ratio [aOR], 4.45 [95% confidence interval {CI},
2.20-8.98]; P < .001) or all 6 immune mediators versus <6 mediators (aOR, 1.77 [95% CI, 1.24-2.52]; P < .001) had greater risk for HIV acquisition. Factor analysis demonstrated that a bacterial factor comprised of 14 high-risk bacterial taxa (aOR, 1.57 [95% CI, 1.27-1.93]; P < 0.001) and the interferon gamma-induced protein 10 (highest quartile: aOR, 3.19 [95% CI, 1.32-7.72]; P = 0.002) contributed to the highest HIV risk.

CONCLUSIONS: Bacterial and host biomarkers for predicting HIV acquisition risk identify women at greatest risk for HIV infection and can focus prevention efforts.},
}

@article {pmid39245683,
year = {2024},
author = {Stathis, CJ and Zhu, H and Carlin, K and Phan, TL and Toomey, D and Hill, JA and Zerr, DM},
title = {A systematic review and meta-analysis of HHV-6 and mortality after hematopoietic cell transplant.},
journal = {Bone marrow transplantation},
volume = {},
number = {},
pages = {},
pmid = {39245683},
issn = {1476-5365},
abstract = {Human herpesvirus-6B (HHV-6B) reactivation has been associated with non-relapse mortality (NRM) and overall mortality (OM) following allogeneic hematopoietic stem cell transplant (HCT). We performed a systematic review and meta-analysis to better quantify the association. Studies were included if they systematically tested a cohort of HCT recipients for HHV-6 infection or reactivation and described mortality for patients with and without HHV-6B. Random effects models were used to assess the pooled effect of HHV-6B positivity on each outcome of interest. Bayesian aggregation was additionally performed if models included 10 or fewer studies. Eight studies were included in the NRM analysis, which demonstrated a significant association between HHV-6 detection and NRM (pooled effect: 1.84; 95% CI: 1.29-2.62) without significant heterogeneity (I[2] = 0.0%, p = 0.55). A Bayesian aggregation of the raw data used to construct the NRM random effects model supported these findings (95% credible interval: 0.15-1.13). Twenty-five studies were included in OM analysis, which showed a significant positive association (pooled effect: 1.37; 95% CI: 1.07-1.76), though considerable heterogeneity was observed (I[2] = 36.7%, p < 0.05). HHV-6 detection is associated with NRM and OM following HCT. Randomized trials are warranted to evaluate if preventing or treating HHV-6B reactivation improves outcomes.},
}

@article {pmid39243788,
year = {2024},
author = {Lama, JR and Duerr, A},
title = {Preventing sexually transmitted infections in the age of PrEP.},
journal = {The lancet. HIV},
volume = {},
number = {},
pages = {},
doi = {10.1016/S2352-3018(24)00236-4},
pmid = {39243788},
issn = {2352-3018},
}

@article {pmid39243704,
year = {2024},
author = {Puschel, K and Rioseco, A and Soto, M and Paz, S and Martinez, J and Soto, G and Faundez, M and Arenas, E and Vescovi, Z and Fuentes, I and Thompson, B and Emery, J},
title = {Implementation of cancer prevention practices in primary care: results of a cohort study in Chile 2018-2022.},
journal = {Public health},
volume = {236},
number = {},
pages = {168-174},
doi = {10.1016/j.puhe.2024.08.006},
pmid = {39243704},
issn = {1476-5616},
abstract = {OBJECTIVES: The burden of cancer is increasing rapidly in Latin America. Primary care has an essential role in cancer prevention, but implementation levels of prevention practices are not well known. This study evaluated implementation levels and associated factors of cancer preventive practices in primary care over time.

STUDY DESIGN: The study incorporated a retrospective multicentre cohort study.

METHODS: A population of 59,949 patients registered at three primary care clinics was followed from January 2018 to December 2022 in Santiago, Chile. We studied human papillomavirus (HPV) and hepatitis B virus (HBV) immunisation, brief counselling for smoking cessation and alcohol consumption, and cervical and breast cancer screening practices. Standardised electronic medical records were utilised as the source of information. Social, clinical, and organisational factors associated with prevention practices were studied.

RESULTS: The cohort attrition level was 17.1%. Most of the population was of a low socioeconomic status, and 70% visited a primary health centre yearly. Implementation rates of immunisation practices were 90.84% for HPV and 80.94% for HBV in 2022. In contrast, brief counselling for smoking and alcohol consumption was below 20% during the study period. Cervical cancer screening decreased by 25.58% between 2018 and 2022, whereas breast cancer screening reached only 41.71% of the target population. Opportunistic medical visits were strongly associated with brief counselling and breast cancer screening.

CONCLUSION: Implementation practices for cancer prevention in a Chilean primary care cohort are high for immunisation and very low for brief counselling and screening practices. A comprehensive non-medical-based model is needed to improve cancer prevention in primary care.},
}

@article {pmid39241960,
year = {2024},
author = {André, F and Cortés, J and Curigliano, G and Modi, S and Li, W and Park, YH and Chung, WP and Kim, SB and Yamashita, T and Pedrini, JL and Im, SA and Tseng, LM and Harbeck, N and Krop, I and Nakatani, S and Tecson, K and Ashfaque, S and Egorov, A and Hurvitz, SA},
title = {A Pooled Analysis of Trastuzumab Deruxtecan in Patients With HER2-Positive Metastatic Breast Cancer With Brain Metastases.},
journal = {Annals of oncology : official journal of the European Society for Medical Oncology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.annonc.2024.08.2347},
pmid = {39241960},
issn = {1569-8041},
abstract = {BACKGROUND: This exploratory pooled analysis investigated the efficacy and safety of trastuzumab deruxtecan (T-DXd) versus comparator treatment in patients with HER2-positive metastatic breast cancer (mBC) with brain metastases (BMs) at baseline, categorized according to previous local treatment.

PATIENTS AND METHODS: T-DXd data were pooled from DESTINY-Breast01/-02/-03. Comparator data, from patients receiving physician's choice therapy and trastuzumab emtansine, were pooled from DESTINY-Breast02 and -03, respectively. Baseline BM status was assessed according to US Food and Drug Administration criteria. Endpoints included intracranial objective response rate (ORR; complete or partial response in brain) per blinded independent central review (BICR) by RECIST v1.1, time to intracranial response, intracranial duration of response (DoR), central nervous system progression-free survival (CNS-PFS) by BICR, overall survival (OS), and safety.

RESULTS: 148 patients who received T-DXd and 83 patients who received comparator treatment had BMs at baseline. In those who were treated with T-DXd, the intracranial ORR of patients with treated/stable and untreated/active BMs was 45.2% and 45.5%, respectively. The median (range) time to intracranial response was 2.8 months (1.1-13.9 months) and 1.5 months (1.2-13.7 months) in patients with treated/stable and untreated/active BMs, respectively. For those with treated/stable BMs, the median (95% CI) intracranial DoR was 12.3 months (9.1-17.9 months), and for those with untreated/active BMs it was 17.5 months (13.6-31.6 months). The median (95% CI) CNS-PFS and OS was 12.3 months (11.1-13.8 months) and not reached (22.1 months-not estimable [NE]) in those with treated/stable BMs, and 18.5 months (13.6-23.3 months) and 30.2 months (21.3 months-NE) in those with untreated/active BMs, respectively. Drug-related TEAEs grade ≥3 were experienced by 43.2% of patients with BMs and 46.4% without BMs with T-DXd.

CONCLUSIONS: T-DXd demonstrated meaningful intracranial efficacy and clinical benefit in OS, with an acceptable and manageable safety profile in patients with HER2-positive mBC with treated/stable and untreated/active BMs.},
}

@article {pmid39241315,
year = {2024},
author = {Bakaloudi, DR and Talukder, R and Makrakis, D and Diamantopoulos, L and Enright, T and Leary, JB and Patgunarajah, U and Thomas, VM and Swami, U and Agarwal, N and Jindal, T and Koshkin, VS and Brown, JR and Barata, P and Murgić, J and Miletić, M and Johnson, J and Zakharia, Y and Hui, G and Drakaki, A and Duran, I and Buznego, LA and Barrera, RM and Castañeda, DM and Rey-Cárdenas, M and Castellano, D and Nguyen, CB and Park, JJ and Alva, A and McKay, RR and Stewart, TF and Epstein, IB and Bellmunt, J and Wright, JL and Gupta, S and Grivas, P and Khaki, AR},
title = {Association of Tumor Mutational Burden and Microsatellite Instability With Response and Outcomes in Patients With Urothelial Carcinoma Treated With Immune Checkpoint Inhibitor.},
journal = {Clinical genitourinary cancer},
volume = {22},
number = {6},
pages = {102198},
doi = {10.1016/j.clgc.2024.102198},
pmid = {39241315},
issn = {1938-0682},
abstract = {BACKGROUND: Microsatellite Instability (MSI) and Tumor Mutational Burden (TMB) are associated with immune checkpoint inhibitor (ICI) efficacy. We examined the association between TMB and MSI status with survival in patients with urothelial carcinoma (UC) treated with ICI.

METHODS: Patients from 15 institutions were treated with ICI monotherapy. Primary endpoint was overall survival and secondary endpoints included observed response rate (ORR), and progression-free (PFS) calculated from ICI initiation. TMB was analyzed as dichotomous (≥10 vs. <10 mut/Mb) and continuous variable.

RESULTS: We identified 411 patients: 203 were treated with ICI 1L/upfront; 104 with 2 + L. For the 1L/upfront: median [m] OS was numerically longer in patients with TMB ≥10 versus TMB <10: mOS 35 versus 26 months (HR = 0.6) and with MSI-H and MSI-S (mOS NR vs. 22 months), though neither association was statistically significant. A statistically significant association was found between TMB (continuous variable) and OS (HR = 0.96, P = .01). For 2 + L: mOS was numerically longer in patients with TMB ≥10 versus TMB <10: (20 vs. 12 months; HR = 0.9); mOS was 12 and 17 months for patients with MSI-H and MSI-S, respectively. Eighty-nine patients received maintenance avelumab (mAV): mOS was longer in patients with TMB ≥10 versus TMB <10: 61 versus 17 months; (HR = 0.2, P = .02) and with MSI-H and MSI-S (NR vs. 24 months).

CONCLUSIONS: Although not reaching statistical significance in several subsets, patients with high TMB and MSI-H had numerically longer OS with ICI, especially with mAV. Further validation is needed.},
}

@article {pmid39241195,
year = {2024},
author = {Walter, RB and Potter, V and Craddock, C},
title = {Allogeneic Hematopoietic Cell Transplantation for Acute Myeloid Leukemia in Adults over 70 years old.},
journal = {Blood},
volume = {},
number = {},
pages = {},
doi = {10.1182/blood.2024024247},
pmid = {39241195},
issn = {1528-0020},
abstract = {The advent of reduced-intensity conditioning regimens, improvements in graft-versus-host disease prophylaxis, and better supportive care have permitted increasing use of allogeneic hematopoietic cell transplantation (allo-HCT) in adults age ≥70 with AML. However, while potentially curative, non-relapse mortality and relapse represent the main causes of treatment failure, highlighting the importance of refining both patient selection and transplant strategies. At the same time, continuously evolving non-transplant therapies and transplant technologies mandate prospective trials (re-)examining the role of allo-HCT and its optimal delivery.},
}

@article {pmid39241101,
year = {2024},
author = {Abousamra, E and Figgins, M and Bedford, T},
title = {Fitness models provide accurate short-term forecasts of SARS-CoV-2 variant frequency.},
journal = {PLoS computational biology},
volume = {20},
number = {9},
pages = {e1012443},
doi = {10.1371/journal.pcbi.1012443},
pmid = {39241101},
issn = {1553-7358},
abstract = {Genomic surveillance of pathogen evolution is essential for public health response, treatment strategies, and vaccine development. In the context of SARS-COV-2, multiple models have been developed including Multinomial Logistic Regression (MLR) describing variant frequency growth as well as Fixed Growth Advantage (FGA), Growth Advantage Random Walk (GARW) and Piantham parameterizations describing variant Rt. These models provide estimates of variant fitness and can be used to forecast changes in variant frequency. We introduce a framework for evaluating real-time forecasts of variant frequencies, and apply this framework to the evolution of SARS-CoV-2 during 2022 in which multiple new viral variants emerged and rapidly spread through the population. We compare models across representative countries with different intensities of genomic surveillance. Retrospective assessment of model accuracy highlights that most models of variant frequency perform well and are able to produce reasonable forecasts. We find that the simple MLR model provides ∼0.6% median absolute error and ∼6% mean absolute error when forecasting 30 days out for countries with robust genomic surveillance. We investigate impacts of sequence quantity and quality across countries on forecast accuracy and conduct systematic downsampling to identify that 1000 sequences per week is fully sufficient for accurate short-term forecasts. We conclude that fitness models represent a useful prognostic tool for short-term evolutionary forecasting.},
}

@article {pmid39241078,
year = {2024},
author = {Nguyen, TNH and Horowitz, LF and Krilov, T and Lockhart, E and Kenerson, HL and Gujral, TS and Yeung, RS and Arroyo-Currás, N and Folch, A},
title = {Label-free, real-time monitoring of cytochrome C drug responses in microdissected tumor biopsies with a multi-well aptasensor platform.},
journal = {Science advances},
volume = {10},
number = {36},
pages = {eadn5875},
pmid = {39241078},
issn = {2375-2548},
mesh = {*Cytochromes c/metabolism ; Humans ; Animals ; Mice ; *Aptamers, Nucleotide ; Neoplasms/drug therapy/pathology/genetics/metabolism ; Biosensing Techniques/methods ; Biopsy ; Cell Line, Tumor ; Apoptosis/drug effects ; Antineoplastic Agents/pharmacology ; },
abstract = {Functional assays on intact tumor biopsies can complement genomics-based approaches for precision oncology, drug testing, and organs-on-chips cancer disease models by capturing key therapeutic response determinants, such as tissue architecture, tumor heterogeneity, and the tumor microenvironment. Most of these assays rely on fluorescent labeling, a semiquantitative method best suited for single-time-point assays or labor-intensive immunostaining analysis. Here, we report integrated aptamer electrochemical sensors for on-chip, real-time monitoring of cytochrome C, a cell death indicator, from intact microdissected tissues with high affinity and specificity. The platform features a multi-well sensor layout and a multiplexed electronic setup. The aptasensors measure increases in cytochrome C in the supernatant of mouse or human microdissected tumors after exposure to various drug treatments. Because of the sensor's high affinity, it primarily tracks rising concentrations of cytochrome C, capturing dynamic changes during apoptosis. This approach could help develop more advanced cancer disease models and apply to other complex in vitro disease models, such as organs-on-chips and organoids.},
}

*Cytochromes c/metabolism
Humans
Animals
Mice
*Aptamers, Nucleotide
Neoplasms/drug therapy/pathology/genetics/metabolism
Biosensing Techniques/methods
Biopsy
Cell Line, Tumor
Apoptosis/drug effects
Antineoplastic Agents/pharmacology

@article {pmid39240995,
year = {2024},
author = {Williamson, BD and Wu, L and Huang, Y and Hudson, A and Gilbert, PB},
title = {Predicting neutralization susceptibility to combination HIV-1 monoclonal broadly neutralizing antibody regimens.},
journal = {PloS one},
volume = {19},
number = {9},
pages = {e0310042},
pmid = {39240995},
issn = {1932-6203},
mesh = {*HIV-1/immunology/drug effects ; Humans ; *Antibodies, Neutralizing/immunology ; *HIV Antibodies/immunology ; *Antibodies, Monoclonal/immunology ; HIV Infections/immunology/drug therapy/virology ; Neutralization Tests/methods ; },
abstract = {Combination monoclonal broadly neutralizing antibodies (bnAbs) are currently being developed for preventing HIV-1 acquisition. Recent work has focused on predicting in vitro neutralization potency of both individual bnAbs and combination regimens against HIV-1 pseudoviruses using Env sequence features. To predict in vitro combination regimen neutralization potency against a given HIV-1 pseudovirus, previous approaches have applied mathematical models to combine individual-bnAb neutralization and have predicted this combined neutralization value; we call this the combine-then-predict (CP) approach. However, prediction performance for some individual bnAbs has exceeded that for the combination, leading to another possibility: combining the individual-bnAb predicted values and using these to predict combination regimen neutralization; we call this the predict-then-combine (PC) approach. We explore both approaches in both simulated data and data from the Los Alamos National Laboratory's Compile, Neutralize, and Tally NAb Panels repository. The CP approach is superior to the PC approach when the neutralization outcome of interest is binary (e.g., neutralization susceptibility, defined as inhibitory 80% concentration < 1 μg/mL). For continuous outcomes, the CP approach performs nearly as well as the PC approach when the individual-bnAb prediction algorithms have strong performance, and is superior to the PC approach when the individual-bnAb prediction algorithms have poor performance. This knowledge may be used when building prediction models for novel antibody combinations in the absence of in vitro neutralization data for the antibody combination; this, in turn, will aid in the evaluation and down-selection of these antibody combinations into prevention efficacy trials.},
}

*HIV-1/immunology/drug effects
Humans
*Antibodies, Neutralizing/immunology
*HIV Antibodies/immunology
*Antibodies, Monoclonal/immunology
HIV Infections/immunology/drug therapy/virology
Neutralization Tests/methods

@article {pmid39240590,
year = {2024},
author = {Nyame, YA},
title = {Editor of the Month UPJ.},
journal = {Urology practice},
volume = {},
number = {},
pages = {101097UPJ0000000000000693},
doi = {10.1097/UPJ.0000000000000693},
pmid = {39240590},
issn = {2352-0787},
}

@article {pmid39240291,
year = {2024},
author = {Donzella, SM and Deubler, E and Patel, AV and Phipps, AI and Zhong, C},
title = {Sleep and cancer mortality in the Cancer Prevention Study-II.},
journal = {Cancer causes & control : CCC},
volume = {},
number = {},
pages = {},
pmid = {39240291},
issn = {1573-7225},
abstract = {PURPOSE: Sleep is a multi-dimensional human function that is associated with cancer outcomes. Previous work on sleep and cancer mortality have not investigated how this relationship varies by sex and cancer site. We investigated the association of sleep duration and perceived insomnia with site-specific and overall cancer mortality among participants in the Cancer Prevention Study-II.

METHODS: Sleep was collected at baseline in 1982 among 1.2 million cancer-free US adults. Cancer-specific mortality was determined through 2018. We used multivariable Cox proportional hazard models to calculate hazard ratios and 95% confidence intervals for overall and site-specific cancer mortality, stratified by sex.

RESULTS: Among 983,105 participants (56% female) followed for a median of 27.9 person-years, there were 146,911 primary cancer deaths. Results from the adjusted model showed short (6 h/night) and long (8 h/night and 9-14 h/night) sleep duration, compared to 7 h/night, were associated with a modest 2%, 2%, and 5% higher risk of overall cancer mortality, respectively, and there was a significant non-linear trend (p-trend < 0.01). This non-linear trend was statistically significant among male (p-trend < 0.001) but not female (p-trend 0.71) participants. For male participants, short and long sleep were associated with higher risk of lung cancer mortality and long sleep was associated with higher risk of colorectal cancer mortality. Perceived insomnia was associated with a 3-7% lower risk of overall cancer mortality.

CONCLUSION: Sleep is important to consider in relation to sex- and site-specific cancer mortality. Future research should investigate other components of sleep in relation to cancer mortality.},
}

@article {pmid39240111,
year = {2024},
author = {Agrawal, P and Knudsen, ML and MacCamy, A and Hurlburt, NK and Khechaduri, A and Salladay, KR and Kher, GM and Kallur Siddaramaiah, L and Stuart, AB and Bontjer, I and Shen, X and Montefiori, D and Gristick, HB and Bjorkman, PJ and Sanders, RW and Pancera, M and Stamatatos, L},
title = {Short CDRL1 in intermediate VRC01-like mAbs is not sufficient to overcome key glycan barriers on HIV-1 Env.},
journal = {Journal of virology},
volume = {},
number = {},
pages = {e0074424},
doi = {10.1128/jvi.00744-24},
pmid = {39240111},
issn = {1098-5514},
abstract = {UNLABELLED: VRC01-class broadly neutralizing antibodies (bnAbs) have been isolated from people with HIV-1, but they have not yet been elicited by vaccination. They are extensively somatically mutated and sometimes accumulate CDRL1 deletions. Such indels may allow VRC01-class antibodies to accommodate the glycans expressed on a conserved N276 N-linked glycosylation site in loop D of the gp120 subunit. These glycans constitute a major obstacle in the development of VRC01-class antibodies, as unmutated antibody forms are unable to accommodate them. Although immunizations of knock-in mice expressing human VRC01-class B-cell receptors (BCRs) with specifically designed Env-derived immunogens lead to the accumulation of somatic mutations in VRC01-class BCRs, CDRL1 deletions are rarely observed, and the elicited antibodies display narrow neutralizing activities. The lack of broad neutralizing potential could be due to the absence of deletions, the lack of appropriate somatic mutations, or both. To address this point, we modified our previously determined prime-boost immunization with a germline-targeting immunogen nanoparticle (426c.Mod.Core), followed by a heterologous core nanoparticle (HxB2.WT.Core), by adding a final boost with a cocktail of various stabilized soluble Env trimers. We isolated VRC01-like antibodies with extensive somatic mutations and, in one case, a seven-amino acid CDRL1 deletion. We generated chimeric antibodies that combine the vaccine-elicited somatic mutations with CDRL1 deletions present in human mature VRC01 bnAbs. We observed that CDRL1 indels did not improve the neutralizing antibody activities. Our study indicates that CDRL1 length by itself is not sufficient for the broadly neutralizing phenotype of this class of antibodies.

IMPORTANCE: HIV-1 broadly neutralizing antibodies will be a key component of an effective HIV-1 vaccine, as they prevent viral acquisition. Over the past decade, numerous broadly neutralizing antibodies (bnAbs) have been isolated from people with HIV. Despite an in-depth knowledge of their structures, epitopes, ontogenies, and, in a few rare cases, their maturation pathways during infection, bnAbs have, so far, not been elicited by vaccination. This necessitates the identification of key obstacles that prevent their elicitation by immunization and overcoming them. Here we examined whether CDRL1 shortening is a prerequisite for the broadly neutralizing potential of VRC01-class bnAbs, which bind within the CD4 receptor binding site of Env. Our findings indicate that CDRL1 shortening by itself is important but not sufficient for the acquisition of neutralization breadth, and suggest that particular combinations of amino acid mutations, not elicited so far by vaccination, are most likely required for the development of such a feature.},
}

@article {pmid39239793,
year = {2024},
author = {Chen, Y and Zhao, L and Jung, SY and Pichardo, MS and Lopez-Pentecost, M and Rohan, TE and Saquib, N and Sun, Y and Tabung, FK and Zheng, T and Wactawski-Wende, J and Manson, JE and Neuhouser, ML and Zhang, X},
title = {Diabetes risk reduction diet and risk of liver cancer and chronic liver disease mortality: A prospective cohort study.},
journal = {Journal of internal medicine},
volume = {},
number = {},
pages = {},
doi = {10.1111/joim.20007},
pmid = {39239793},
issn = {1365-2796},
support = {/HL/NHLBI NIH HHS/United States ; /NH/NIH HHS/United States ; 75N92021D00001/HL/NHLBI NIH HHS/United States ; 75N92021D00002/HL/NHLBI NIH HHS/United States ; 75N92021D00003/WH/WHI NIH HHS/United States ; 75N92021D00004/WH/WHI NIH HHS/United States ; 75N92021D00005/WH/WHI NIH HHS/United States ; R21 CA238651/CA/NCI NIH HHS/United States ; R21 CA252962/CA/NCI NIH HHS/United States ; R37 CA262299/CA/NCI NIH HHS/United States ; U01 CA259208/CA/NCI NIH HHS/United States ; U01 CA272452/CA/NCI NIH HHS/United States ; RSG-17-190-01-NEC//American Cancer Society Research Scholar Award/ ; PASD-221003396-01//American Cancer Society Interdisciplinary Team Award/ ; },
abstract = {BACKGROUND: We aimed to prospectively evaluate the association between a diabetes risk reduction diet (DRRD) score and the risk of liver cancer development and chronic liver disease-specific mortality.

METHODS: We included 98,786 postmenopausal women from the Women's Health Initiative-Observational Study and the usual diet arm of the Diet Modification trial. The DRRD score was derived from eight factors: high intakes of dietary fiber, coffee, nuts, polyunsaturated fatty acids, low intakes of red and processed meat, foods with high glycemic index, sugar-sweetened beverages (SSBs), and trans fat based on a validated Food-Frequency Questionnaire administered at baseline (1993-1998). Multivariable hazard ratios (HRs) and 95% confidence intervals (CIs) for liver cancer incidence and chronic liver disease mortality were estimated using Cox proportional hazards regression models.

RESULTS AND CONCLUSION: After a median follow-up of 22.0 years, 216 incident liver cancer cases and 153 chronic liver disease deaths were confirmed. A higher DRRD score was significantly associated with a reduced risk of developing liver cancer (HRTertile 3 vs. Tertile 1 = 0.69; 95% CI: 0.49-0.97; Ptrend = 0.03) and chronic liver disease mortality (HRT3 vs. T1 = 0.54; 95% CI: 0.35-0.82; Ptrend = 0.003). We further found inverse associations with dietary fiber and coffee, and positive associations with dietary glycemic index, SSBs, and trans fat. A higher DRRD score was associated with reduced risk of developing liver cancer and chronic liver disease mortality among postmenopausal women.},
}

@article {pmid39238853,
year = {2024},
author = {Leedy, DJ and Voit, JM and Rillamas-Sun, E and Kwan, ML and Shen, H and Li, S and Laurent, CA and Rana, JS and Lee, VS and Roh, JM and Huang, Y and Greenlee, H and Cheng, RK},
title = {Blood Pressure and Cardiovascular Risk in Women With Breast Cancer: The Pathways Heart Study.},
journal = {JACC. Advances},
volume = {3},
number = {9},
pages = {101207},
pmid = {39238853},
issn = {2772-963X},
abstract = {BACKGROUND: Hypertension is an important contributor to cardiovascular disease (CVD) in breast cancer (BC) survivors; however, research on blood pressure (BP) and CVD outcomes in BC survivors is limited.

OBJECTIVES: The purpose of this study was to better characterize the association between BP and CVD in a large, longitudinal cohort of BC patients.

METHODS: Women with invasive BC diagnosed from 2005 to 2013 at Kaiser Permanente Northern California were matched 1:5 to women without BC. Patient data were obtained from electronic health records. Multivariable Cox regression and penalized spline models were used to explore the linear and nonlinear relationship of systolic blood pressure (SBP) and diastolic blood pressure (DBP) on CVD outcomes.

RESULTS: BC cases (n = 12,713) and controls (n = 55,886) had median follow-up of 9.6 years (IQR: 5.0-11.9 years). Women with BC had a mean age of 60.6 years; 64.8% were non-Hispanic White. For ischemic heart disease (IHD), every 10 mmHg increase in SBP and DBP was associated with 1.23 (95% CI: 1.14-1.33) and 1.10 (95% CI: 0.98-1.24) risk, respectively, in women with BC. For stroke, every 10 mmHg increase in SBP and DBP was associated with a 1.45 (95% CI: 1.34-1.58) and 1.91 (95% CI: 1.68-2.18) risk, respectively. A U-shaped relationship was observed between heart failure/cardiomyopathy and BP. The associations between BP and risk of IHD, stroke, and any primary CVD were not statistically different comparing women with BC to controls, but risks varied by BC status for heart failure/cardiomyopathy (P for interaction = 0.01).

CONCLUSIONS: Women with and without BC showed similar risks for IHD, stroke, and any primary CVD suggesting similar BP targets should be pursued regardless of BC survivorship status.},
}

@article {pmid39238483,
year = {2024},
author = {Vitanza, NA and Choe, M and Brown, C and Beebe, A and Kong, A and Rogers, L and Jacob, S and Mano, E and Abuan, K and Mgebroff, S and Lindgren, C and Gustafson, JA and Wilson, AL and Noll, A and Ronsley, R and Crotty, EE and Leary, SES and Foster, JB and Pinto, N and Gust, J and Gardner, RA and Park, JR and Jensen, MC},
title = {Locoregional CAR T Cells for the Treatment of CNS Tumors in Children: Investigational Drug Service Pharmacy Activities.},
journal = {Journal of hematology oncology pharmacy},
volume = {14},
number = {4},
pages = {148-154},
pmid = {39238483},
issn = {2164-1153},
support = {U01 TR002487/TR/NCATS NIH HHS/United States ; },
abstract = {BACKGROUND: A major obstacle in translating the therapeutic potential of chimeric antigen receptor (CAR) T cells to children with central nervous system (CNS) tumors is the blood-brain barrier. To overcome this limitation, preclinical and clinical studies have supported the use of repeated, locoregional intracranial CAR T-cell delivery. However, there is limited literature available describing the process for the involvement of an investigational drug service (IDS) pharmacy, particularly in the setting of a children's hospital with outpatient dosing for CNS tumors.

OBJECTIVES: To describe Seattle Children's Hospital's experience in clinically producing CAR T cells and the implementation of IDS pharmacy practices used to deliver more than 300 intracranial CAR T-cell doses to children, as well as to share how we refined the processing techniques from CAR T-cell generation to the thawing of fractionated doses for intracranial delivery.

METHODS: Autologous CD4+ and CD8+ T cells were collected and transduced to express HER2, EGFR, or B7-H3-specific CAR T cells. Cryopreserved CAR T cells were thawed by the IDS pharmacy before intracranial delivery to patients with recurrent/refractory CNS tumors or with diffuse intrinsic pontine glioma/diffuse midline glioma.

RESULTS: The use of a thaw-and-dilute procedure for cryopreserved individual CAR T-cell doses provides reliable viability and is more efficient than typical thaw-and-wash protocols. Cell viability with the thaw-and-dilute protocol was approximately 75% and was always within 10% of the viability assessed at cryopreservation. Cell viability was preserved through 6 hours after thawing, which exceeded the 1-hour time frame from thawing to infusion.

CONCLUSION: As the field of adoptive immunotherapy grows and continues to bring hope to patients with fatal CNS malignancies, it is critical to focus on improving the preparatory steps for CAR T-cell delivery.},
}

@article {pmid39236759,
year = {2024},
author = {Streiff, MB and Holmstrom, B and Angelini, D and Ashrani, A and Buckner, T and Diep, R and Fertrin, KY and Fogerty, AE and Crestani, NG and Gangaraju, R and Rojas-Hernandez, C and Goldhaber, SZ and Ibrahim, I and Kubal, T and Leavitt, AD and Lim, M and Mann, J and Mantha, S and Morton, C and Nester, A and O'Brien, A and Ortel, TL and Pine, A and Pishko, A and Ranade, M and Salmasi, A and Schaefer, J and Williams, E and Wool, G and Wun, T and Montgomery, S and Nguyen, J and Freedman-Cass, D and Sliker, B},
title = {Cancer-Associated Venous Thromboembolic Disease, Version 2.2024, NCCN Clinical Practice Guidelines in Oncology.},
journal = {Journal of the National Comprehensive Cancer Network : JNCCN},
volume = {22},
number = {7},
pages = {483-506},
doi = {10.6004/jnccn.2024.0046},
pmid = {39236759},
issn = {1540-1413},
mesh = {Humans ; *Venous Thromboembolism/etiology/diagnosis/therapy/prevention & control ; *Neoplasms/complications/therapy/diagnosis ; Medical Oncology/standards/methods ; Anticoagulants/therapeutic use ; Disease Management ; },
abstract = {The NCCN Guidelines for Cancer-Associated Venous Thromboembolic Disease provide strategies for the prevention, diagnosis, and treatment of venous thromboembolism (VTE) in adult patients with cancer. VTE is a common and life-threatening condition in patients with cancer, and its management often requires multidisciplinary efforts. The NCCN panel is comprised of specialists spanning various fields, including cardiology, hematology, medical oncology, internal medicine, interventional radiology, and pharmacology. The content featured in this issue specifically addresses the evaluation and recommended treatment options outlined in the NCCN Guidelines for the diverse subtypes of cancer-associated VTE.},
}

Humans
*Venous Thromboembolism/etiology/diagnosis/therapy/prevention & control
*Neoplasms/complications/therapy/diagnosis
Medical Oncology/standards/methods
Anticoagulants/therapeutic use
Disease Management

@article {pmid39236750,
year = {2024},
author = {Ness, RM and Llor, X and Abbass, MA and Bishu, S and Chen, CT and Cooper, G and Early, DS and Friedman, M and Fudman, D and Giardiello, FM and Glaser, K and Gurudu, S and Hall, M and Huang, LC and Issaka, R and Katona, B and Kidambi, T and Lazenby, AJ and Maratt, J and Markowitz, AJ and Marsano, J and May, FP and Mayer, RJ and Olortegui, K and Patel, S and Peter, S and Porter, LD and Shafi, M and Stanich, PP and Terdiman, J and Vu, P and Weiss, JM and Wood, E and Cassara, CJ and Sambandam, V},
title = {NCCN Guidelines® Insights: Colorectal Cancer Screening, Version 1.2024.},
journal = {Journal of the National Comprehensive Cancer Network : JNCCN},
volume = {22},
number = {7},
pages = {438-446},
doi = {10.6004/jnccn.2024.0047},
pmid = {39236750},
issn = {1540-1413},
mesh = {Humans ; *Colorectal Neoplasms/diagnosis ; *Early Detection of Cancer/standards/methods ; Mass Screening/methods/standards ; },
abstract = {The NCCN Guidelines for Colorectal Cancer (CRC) Screening describe various colorectal screening modalities as well as recommended screening schedules for patients at average or increased risk of developing sporadic CRC. They are intended to aid physicians with clinical decision-making regarding CRC screening for patients without defined genetic syndromes. These NCCN Guidelines Insights focus on select recent updates to the NCCN Guidelines, including a section on primary and secondary CRC prevention, and provide context for the panel's recommendations regarding the age at which to initiate screening in average-risk individuals and those with increased risk based on personal history of childhood, adolescent, and young adult cancer.},
}

Humans
*Colorectal Neoplasms/diagnosis
*Early Detection of Cancer/standards/methods
Mass Screening/methods/standards

@article {pmid39236733,
year = {2024},
author = {Isa, F and Gonzalez Ortiz, AM and Meyer, J and Hamilton, JD and Olenchock, BA and Brackin, T and Ganguly, S and Forleo-Neto, E and Faria, L and Heirman, I and Marovich, M and Hutter, J and Polakowski, L and Irvin, SC and Thakur, M and Hooper, AT and Baum, A and Petro, CD and Fakih, FA and McElrath, MJ and De Rosa, SC and Cohen, KW and Williams, LD and Hellman, CA and Odeh, AJ and Patel, AH and Tomaras, GD and Geba, GP and Kyratsous, CA and Musser, B and Yancopoulos, GD and Herman, GA and , },
title = {Effect of timing of casirivimab and imdevimab administration relative to mRNA-1273 COVID-19 vaccination on vaccine-induced SARS-CoV-2 neutralising antibody responses: a prospective, open-label, phase 2, randomised controlled trial.},
journal = {The Lancet. Infectious diseases},
volume = {},
number = {},
pages = {},
doi = {10.1016/S1473-3099(24)00421-3},
pmid = {39236733},
issn = {1474-4457},
abstract = {BACKGROUND: Deeper insight is needed on how monoclonal antibodies (mAbs) affect vaccine-mediated immune responses when targeting the same protein. We describe the first prospective randomised trial designed to understand mAb-mediated alterations in vaccine-induced immune responses to SARS-CoV-2 spike protein epitopes.

METHODS: This randomised, open-label, parallel-group study assessed the potential interaction of a mAb combination, casirivimab and imdevimab, with a vaccine, Moderna's mRNA-1273, in healthy SARS-CoV-2 immunologically naive, seronegative adults at six centres in the USA. Participants were randomly assigned (per prespecified randomisation ratios within enrolment waves) according to a computer-generated randomisation scheme, stratified by age (<65 years and ≥65 years), to various intravenous or subcutaneous doses of casirivimab and imdevimab before, after, or at the same time as mRNA-1273 or to mRNA-1273 only. The doses of casirivimab and imdevimab were chosen to mimic various time intervals between receipt of 1200 mg of the mAb and the first dose of a primary series with mRNA-1273. The primary endpoint was vaccine-induced 50% inhibitory dilution neutralising antibody titres to SARS-CoV-2 spike protein, 56 days after the first vaccination. Secondary endpoints included vaccine-induced total antibodies to SARS-CoV-2 antigens and incidence of treatment-emergent adverse events. Exploratory endpoints included blood-derived T-cell and B-cell responses. The per-protocol set was used for the analysis of the primary endpoint and included all randomly assigned participants who received both doses of the vaccine and completed the injection or infusion of casirivimab and imdevimab per protocol, had no evidence of SARS-CoV-2 infection in the past or in the 56 days after the first dose of vaccine, and did not receive any intervention outside of the study that could alter the immune response. Safety was assessed in the safety analysis set, which included all randomly assigned participants who had received one or more doses of mRNA-1273 or any study drug, and analysed based on treatment received. The study is registered with ClinicalTrials.gov, NCT04852978, and is complete.

FINDINGS: Between April 29, 2021, and Nov 21, 2022, 807 participants were assessed for eligibility and 295 were randomly assigned. 293 participants were included in the safety analysis set and 260 were included in the per-protocol set. All vaccinated participants developed neutralising antibodies to SARS-CoV-2, with median titres above the published protective threshold (100 IU/mL) against the SARS-CoV-2 D614G variant (considered a reference strain at the time the initial COVID-19 vaccines were developed). Titres were decreased up to 4-fold (median titres 280-450 IU/mL for casirivimab and imdevimab vs 1160 IU/mL for vaccine only on day 56) when casirivimab and imdevimab was given 85 days or less before vaccination (150-1200 mg intravenously) or co-administered subcutaneously (600 mg or 1200 mg) with vaccination. Minimal reduction in neutralisation titres was observed in the 48 mg and 12 mg intravenous groups, corresponding to receipt of casirivimab and imdevimab 113 days and 169 days, respectively, before vaccination, and when administering the vaccine 6 days before the mAb. Across all groups, mAbs had a minimal effect on vaccine-induced total antibodies and T-cell responses to the spike protein. Casirivimab and imdevimab plus mRNA-1273 was generally well tolerated; a slight increase in treatment-emergent adverse events was observed in the casirivimab and imdevimab plus vaccine groups versus the vaccine-only group.

INTERPRETATION: Casirivimab and imdevimab administration before or at the time of COVID-19 vaccination reduced the elicitation of SARS-CoV-2 neutralising antibodies, but minimal effect was observed when vaccination occurred before mAb administration. Although the clinical significance of this decrease in neutralisation is unclear, this evidence suggests that further investigation of potential interactions could be warranted before concurrent clinical use of mAbs and vaccines targeting the same viral proteins as their main modes of action for the prevention or treatment of infectious diseases.

FUNDING: Regeneron Pharmaceuticals and F Hoffmann-La Roche.},
}

@article {pmid39236556,
year = {2024},
author = {Kenny, A and van Duijn, J and Dintwe, O and Heptinstall, J and Burnham, R and Sawant, S and Zhang, L and Mielke, D and Khuzwayo, S and Omar, FL and Stanfield-Oakley, S and Keyes, T and Dunn, B and Goodman, D and Fong, Y and Benkeser, D and Zou, R and Hural, J and Hyrien, O and Juraska, M and Luedtke, A and van der Laan, L and Giorgi, EE and Magaret, C and Carpp, LN and Pattacini, L and van de Kerkhof, T and Korber, B and Willems, W and Fisher, LH and Schuitemaker, H and Swann, E and Kublin, JG and Pau, MG and Buchbinder, S and Tomaka, F and Nijs, S and Lavreys, L and Gelderblom, HC and Corey, L and Mngadi, K and Gray, GE and Borducchi, E and Hendriks, J and Seaton, KE and Zolla-Pazner, S and Barouch, DH and Ferrari, G and De Rosa, SC and McElrath, MJ and Andersen-Nissen, E and Stieh, DJ and Tomaras, GD and Gilbert, PB and , },
title = {Immune correlates analysis of the Imbokodo (HVTN 705/HPX2008) efficacy trial of a mosaic HIV-1 vaccine regimen evaluated in Southern African people assigned female sex at birth: a two-phase case-control study.},
journal = {EBioMedicine},
volume = {108},
number = {},
pages = {105320},
doi = {10.1016/j.ebiom.2024.105320},
pmid = {39236556},
issn = {2352-3964},
abstract = {BACKGROUND: The HVTN 705 Imbokodo trial of 2636 people without HIV and assigned female sex at birth, conducted in southern Africa, evaluated a heterologous HIV-1 vaccine regimen: mosaic adenovirus 26-based vaccine (Ad26.Mos4.HIV) at Months 0, 3, 6, 12 and alum-adjuvanted clade C gp140 at Months 6, 12. Per-protocol vaccine efficacy (VE) against HIV-1 diagnosis from seven to 24 months was 14.1% (95% CI: -22.0% to 39.5%). Immune correlates analysis was performed for markers selected based on prior evidence in efficacy trials and/or nonhuman primate models.

METHODS: Humoral and cellular immune response markers at Month 7 were evaluated as immune correlates of risk and of protection in a breakthrough case-control cohort (n = 52 cases, 246 non-cases). Primary markers were IgG binding to vaccine-strain gp140, IgG3 binding to diverse Env antigens (IgG3 Env breadth), IgG3 binding to diverse V1V2 antigens (IgG3 V1V2 breadth), antibody-dependent phagocytosis against the vaccine-strain gp140, Env-specific CD4+ and CD8+ T-cell responses, and multi-epitope functions.

FINDINGS: No immune markers were statistically significant correlates of risk. IgG3 V1V2 breadth trended toward an inverse association: hazard ratio 0.70 (95% CI: 0.36 to 1.35; p = 0.29) per 10-fold increase and 0.51 (95% CI: 0.21 to 1.24; p = 0.14) in a Cox model with all primary markers. The VE estimate was 11.8% (95% CI: -17.9% to 34.0%) at all IgG3 V1V2 breadth values below 667 weighted geometric mean net MFI; just above this value, the VE estimate sharply increased to 62.6% (95% CI: -17.9% to 89.6%), and further increased to 80.9% (95% CI: -17.9% to 99.5%) at 1471 MFI, the 95th percentile of the marker distribution. Mediation analysis yielded a VE of 35.7% (95% CI: 15.0% to 51.3%) attributable to the vaccine's impact on this marker.

INTERPRETATION: The trend in association of greater IgG3 V1V2 antibody breadth with lower likelihood of HIV acquisition is consistent with the identification of antibodies against V1V2 as immune correlates in three other HIV vaccine efficacy trials and suggests that a greater emphasis should be placed on studying this region in the HIV-1 envelope as a vaccine immunogen.

FUNDING: National Institute of Allergy and Infectious Diseases and Janssen Vaccines & Prevention BV.},
}

@article {pmid39235868,
year = {2024},
author = {Piha-Paul, S and Olwill, SA and Hamilton, E and Tolcher, A and Pohlmann, P and Liu, SV and Wurzenberger, C and Hasenkamp, LC and Hansbauer, EM and Shroff, R and Hurvitz, S and Krishnamurthy, A and Patnaik, A and Hahn, N and Kumar, R and Duerr, M and Zettl, M and Aviano, K and Matis, L and Bruns, I and Ku, G},
title = {A First-in-Human Study of cinrebafusp alfa, a HER2/4-1BB Bispecific Molecule, in Patients with HER2-Positive Advanced Solid Malignancies.},
journal = {Clinical cancer research : an official journal of the American Association for Cancer Research},
volume = {},
number = {},
pages = {},
doi = {10.1158/1078-0432.CCR-24-1552},
pmid = {39235868},
issn = {1557-3265},
abstract = {PURPOSE: 4-1BB (CD137) is a costimulatory immune receptor expressed on activated T cells, activated B cells, natural killer cells and tumor-infiltrating lymphocytes, making it a promising target for cancer immunotherapy. Cinrebafusp alfa, a monoclonal antibody-like bispecific protein targeting HER2 and 4-1BB, aims to localize 4-1BB activation to HER2-positive tumors. This study evaluated the safety, tolerability, and preliminary efficacy of cinrebafusp alfa in patients with previously treated HER2-positive malignancies.

EXPERIMENTAL DESIGN: This was a multi-center dose escalation study involving patients with HER2-positive malignancies who had received prior treatment. The study assessed the safety and efficacy of cinrebafusp alfa across various dose levels. Patients were assigned to different cohorts, and antitumor responses were evaluated. The study aimed to determine the maximum tolerated dose (MTD) and to observe any clinical activity at different dose levels.

RESULTS: Out of 40 evaluable patients in the 'active dose' efficacy cohorts, 5 showed an antitumor response, resulting in an overall response rate (ORR) of 12.5% and a disease control rate of 52.5%. Clinical activity was observed at the 8 mg/kg and 18 mg/kg dose levels, with confirmed objective response rates of 28.6% and 25.0%, respectively. Cinrebafusp alfa was safe and tolerable, with Grade ≤2 infusion-related reactions being the most frequent treatment-related adverse event. MTD was not reached during the study.

CONCLUSION: Cinrebafusp alfa demonstrates promising activity in patients with HER2-positive malignancies who have progressed on prior HER2-targeting regimens. Its acceptable safety profile suggests it could be a treatment option for patients not responding to existing HER2-directed therapies.},
}

@article {pmid39235529,
year = {2024},
author = {Hahn, WO and Parks, KR and Shen, M and Ozorowski, G and Janes, H and Ballweber-Fleming, L and Woodward Davis, AS and Duplessis, C and Tomai, M and Dey, AK and Sagawa, ZK and De Rosa, SC and Seese, A and Kallur Siddaramaiah, L and Stamatatos, L and Lee, WH and Sewall, LM and Karlinsey, D and Turner, HL and Rubin, V and Furth, S and MacPhee, K and Duff, M and Corey, L and Keefer, MC and Edupuganti, S and Frank, I and Maenza, J and Baden, LR and Hyrien, O and Sanders, RW and Moore, JP and Ward, AB and Tomaras, GD and Montefiori, DC and Rouphael, N and McElrath, MJ},
title = {Use of 3M-052-AF with Alum adjuvant in HIV trimer vaccine induces human autologous neutralizing antibodies.},
journal = {The Journal of experimental medicine},
volume = {221},
number = {10},
pages = {},
doi = {10.1084/jem.20240604},
pmid = {39235529},
issn = {1540-9538},
support = {UM1 AI068614/AI/NIAID NIH HHS/United States ; OPP1107954//Gates Foundation/ ; },
mesh = {Humans ; *Antibodies, Neutralizing/immunology ; *AIDS Vaccines/immunology/administration & dosage ; *Alum Compounds/administration & dosage ; Adult ; *Adjuvants, Immunologic/administration & dosage ; *env Gene Products, Human Immunodeficiency Virus/immunology ; HIV Antibodies/immunology ; Female ; HIV-1/immunology ; Male ; HIV Infections/immunology/prevention & control ; B-Lymphocytes/immunology ; Adjuvants, Vaccine ; Middle Aged ; Young Adult ; CD4-Positive T-Lymphocytes/immunology ; },
abstract = {Stabilized trimers preserving the native-like HIV envelope structure may be key components of a preventive HIV vaccine regimen to induce broadly neutralizing antibodies (bnAbs). We evaluated trimeric BG505 SOSIP.664 gp140 formulated with a novel TLR7/8 signaling adjuvant, 3M-052-AF/Alum, for safety, adjuvant dose-finding, and immunogenicity in a first-in-healthy adult (n = 17), randomized, and placebo-controlled trial (HVTN 137A). The vaccine regimen appeared safe. Robust, trimer-specific antibody, and B cell and CD4+ T cell responses emerged after vaccination. Five vaccinees developed serum autologous tier 2 nAbs (ID50 titer, 1:28-1:8647) after two to three doses targeting C3/V5 and/or V1/V2/V3 Env regions by electron microscopy and mutated pseudovirus-based neutralization analyses. Trimer-specific, B cell-derived monoclonal antibody activities confirmed these results and showed weak heterologous neutralization in the strongest responder. Our findings demonstrate the clinical utility of the 3M-052-AF/Alum adjuvant and support further improvements of trimer-based Env immunogens to focus responses on multiple broad nAb epitopes.},
}

Humans
*Antibodies, Neutralizing/immunology
*AIDS Vaccines/immunology/administration & dosage
*Alum Compounds/administration & dosage
Adult
*Adjuvants, Immunologic/administration & dosage
*env Gene Products, Human Immunodeficiency Virus/immunology
HIV Antibodies/immunology
Female
HIV-1/immunology
Male
HIV Infections/immunology/prevention & control
B-Lymphocytes/immunology
Adjuvants, Vaccine
Middle Aged
Young Adult
CD4-Positive T-Lymphocytes/immunology

@article {pmid39235112,
year = {2024},
author = {Kwendakwema, CN and Sabo, MC and Roberts, ST and Masese, L and McClelland, RS and Shafi, J and Lehman, DA and Overbaugh, J and Graham, SM},
title = {Sexual Violence, Genital Cytokines, and Colposcopy Findings: A Cross-Sectional Study of Women Engaged in Sex Work in Mombasa, Kenya.},
journal = {Sexually transmitted diseases},
volume = {},
number = {},
pages = {},
doi = {10.1097/OLQ.0000000000002070},
pmid = {39235112},
issn = {1537-4521},
abstract = {BACKGROUND: Sexual violence (SV) increases HIV susceptibility in a sustained manner. This study evaluated genital cytokines and colposcopy findings in women reporting both recent and more remote SV.Methods: A cross-sectional study of HIV-1 negative Kenyan women who engage in sex work (WESW) was performed. Cervicovaginal fluid was collected by menstrual cup and cytokines (IFNγ, TNFα, IL-1β, IL-6, IL-10, MIP-1α, MIP-1β and CXCL10) measured using chemiluminescence. Cervical injury was assessed by colposcopy. Associations between recent (≤30 days prior), more remote (>30 days prior) and no (reference category) SV exposure and cytokine concentrations were evaluated using linear regression.

RESULTS: Among 282 participants, 25 (8.9%) reported recent SV and 123 (43.6%) reported more remote SV. Only two cytokines (IL-10 and CXCL10) were associated with the 3-category SV variable in bivariable modeling at the pre-specified cut-off (p < 0.2) and carried forward. In multivariable analyses, more remote SV (β = 0.72, 95% CI 0.06, 1.38; p = 0.03), but not recent SV (β = 0.20, 95%CI -0.99, 1.39; p = 0.74) was associated with cervicovaginal IL-10 compared to no SV. Recent (β = 0.36, 95% CI -0.94, 1.67; p = 0.58) and more remote (β = 0.51, 95% CI -0.21, 1.24; p = 0.16) SV were not associated with CXCL10 compared to no SV. Cervical epithelial friability (χ2 = 1.3, p = 0.51), erythema (χ2 = 2.9, p = 0.24), vascular disruption (χ2 = 1.4; p = 0.50), epithelial disruption (χ2 = 2.6, p = 0.27), or any colposcopy finding (χ2 = 1.2, p = 0.54) were not associated with SV category by chi-square test.

CONCLUSIONS: The mechanism linking SV to sustained increases in HIV susceptibility may not be related to persistent genital inflammation or injury.},
}

@article {pmid39234871,
year = {2024},
author = {Mercadal, S and Ahn, KW and Allbee-Johnson, M and Ganguly, S and Geethakumari, PR and Hong, S and Malone, A and Murthy, H and Pawarode, A and Sica, AR and Solh, M and Ustun, C and Shadman, M and Sauter, CS and Hamadani, M and Herrera, AF and Lee, CJ},
title = {Outcomes of patients with primary central nervous system lymphoma following CD19-targeted chimeric antigen receptor T-cell therapy.},
journal = {Haematologica},
volume = {},
number = {},
pages = {},
doi = {10.3324/haematol.2024.285613},
pmid = {39234871},
issn = {1592-8721},
}

@article {pmid39234862,
year = {2024},
author = {Phillips, T and Wang, M and Robak, T and Gallinson, D and Stevens, D and Patel, K and Ramadan, S and Wun, CC and Jurczak, W and Smith, SD},
title = {Safety and efficacy of acalabrutinib plus bendamustine and rituximab in patients with treatment-naive or relapsed / refractory mantle cell lymphoma: phase Ib trial.},
journal = {Haematologica},
volume = {},
number = {},
pages = {},
doi = {10.3324/haematol.2023.284896},
pmid = {39234862},
issn = {1592-8721},
abstract = {This multicenter, open-label, phase 1b study (ACE-LY-106) assessed the safety and efficacy of acalabrutinib, bendamustine, and rituximab (ABR) in treatment-naive (TN) and relapsed or refractory (R/R) mantle cell lymphoma (MCL). Patients received acalabrutinib from cycle 1 until disease progression or treatment discontinuation, bendamustine on days 1 and 2 of each cycle for up to 6 cycles, and rituximab on day 1 of each cycle for 6 cycles, continuing every other cycle from cycle 8 for 12 additional doses (TN cohort). Eighteen patients enrolled in the TN and 20 in the R/R cohort. Median duration of exposure to acalabrutinib was 34.0 and 14.6 months in the TN and R/R cohorts, respectively. No new safety risks were identified, and most adverse events (AEs) were grades 1 or 2. Thirteen patients from the TN cohort (72.2%) and 17 patients from the R/R cohort (85.0%) reported grade 3-4 AEs, most commonly neutropenia (TN: 38.9%, R/R: 50.0%). AEs leading to death were pneumonitis (n=1, TN cohort), COVID-19, and cerebrospinal meningitis (n=1 each, R/R cohort). Overall response was 94.4% and 85.0% in the TN and R/R cohorts, respectively; complete response rates were 77.8% and 70.0%, respectively. After a median follow-up of 47.6 months, median progression-free survival (PFS) and overall survival (OS) were not reached in the TN cohort. After a median follow-up of 20.4 months, median PFS was 28.6 months and OS was not reached in the R/R cohort. Results indicate that ABR was safe and efficacious, supporting further study in patients with TN MCL. ClinicalTrials.gov identifier: NCT02717624.},
}

@article {pmid39233917,
year = {2024},
author = {Wesselink, E and Gauderman, W and Berndt, SI and Brenner, H and Buchanan, DD and Campbell, PT and Chan, AT and Chang-Claude, J and Cotterchoi, M and Gunter, MJ and Hoffmeister, M and Joshi, AD and Newton, CC and Pai, RK and Pellatt, AJ and Phipps, AI and Song, M and Um, CY and van Guelpen, B and White, E and Peters, U and van Duijnhoven, FJB},
title = {Calcium intake and genetic variants in the calcium sensing receptor in relation to colorectal cancer mortality: an international consortium study of 18,952 patients.},
journal = {BJC reports},
volume = {2},
number = {1},
pages = {63},
pmid = {39233917},
issn = {2731-9377},
abstract = {BACKGROUND: Research on calcium intake as well as variants in the calcium sensor receptor (CaSR) gene and their interaction in relation to CRC survival is still limited.

METHODS: Data from 18,952 CRC patients, were included. Associations between primarily pre-diagnostic dietary (n = 13.085), supplemental (n = 11,837), total calcium intake (n = 5970) as well as 325 single nucleotide polymorphisms (SNPs) of the CaSR gene (n = 15,734) in relation to CRC-specific and all-cause mortality were assessed using Cox proportional hazard models. Also interactions between calcium intake and variants in the CaSR gene were assessed.

RESULTS: During a median follow-up of 4.8 years (IQR 2.4-8.4), 6801 deaths occurred, of which 4194 related to CRC. For all-cause mortality, no associations were observed for the highest compared to the lowest sex- and study-specific quartile of dietary (HR 1.00, 95%CI 0.92-1.09), supplemental (HR 0.97, 95%CI 0.89-1.06) and total calcium intake (HR 0.99, 95%CI 0.88-1.11). No associations with CRC-specific mortality were observed either. Interactions were observed between supplemental calcium intake and several SNPs of the CaSR gene.

CONCLUSION: Calcium intake was not associated with all-cause or CRC-specific mortality in CRC patients. The association between supplemental calcium intake and all-cause and CRC-specific mortality may be modified by genetic variants in the CaSR gene.},
}

@article {pmid39233850,
year = {2024},
author = {Roos, CR and Bricker, J and Kiluk, B and Trull, TJ and Bowen, S and Witkiewitz, K and Kober, H},
title = {A smartphone app-based mindfulness intervention to enhance recovery from substance use disorders: Protocol for a pilot feasibility randomized controlled trial.},
journal = {Contemporary clinical trials communications},
volume = {41},
number = {},
pages = {101338},
pmid = {39233850},
issn = {2451-8654},
abstract = {BACKGROUND: Poor long-term recovery outcomes after treatment (e.g., readmission to inpatient treatment) are common among individuals with substance use disorders (SUDs). In-person mindfulness-based treatments (MBTs) are efficacious for SUDs and may improve recovery outcomes. However, existing MBTs for SUD have limited public health reach, and thus scalable delivery methods are needed. A digitally-delivered MBT for SUDs may hold promise.

METHODS: We recently developed Mindful Journey, a smartphone app-based adjunctive MBT for improving long-term recovery outcomes. In this paper, we present details on the app and describe the protocol for a single-site pilot feasibility randomized controlled trial of Mindful Journey. In this trial, individuals (n = 34) in an early phase of outpatient treatment for SUDs will be randomized to either treatment-as-usual (TAU) plus Mindful Journey, or TAU only. The trial will focus on testing the feasibility (e.g., engagement) and acceptability of the app (e.g., perceived usability and helpfulness for recovery), as well as feasibility of study procedures (e.g., assessment completion). The trial will incorporate ecological momentary assessment before and after treatment to assess mechanisms in real-time, including mindfulness, craving, difficulties with negative emotion regulation, and savoring. To examine the sensitivity to change of outcomes (substance use, substance-related problems, and psychological distress) and mechanism variables (noted above), we will test within-treatment-condition changes over time.

DISCUSSION: The proposed pilot trial will provide important preliminary data on whether Mindful Journey is feasible and acceptable among individuals with SUDs.

TRIAL REGISTRATION: ClinicalTrials.gov NCT05109507.},
}

@article {pmid39233462,
year = {2024},
author = {Reiner, AS and Knight, JA and John, EM and Lynch, CF and Malone, KE and Liang, X and Woods, M and Root, JC and Bernstein, JL},
title = {Reply to "Critical analysis of Reiner et al.'s study on agreement of medical record abstraction and self-report of breast cancer treatment".},
journal = {Cancer},
volume = {},
number = {},
pages = {},
doi = {10.1002/cncr.35549},
pmid = {39233462},
issn = {1097-0142},
support = {CA008748/NH/NIH HHS/United States ; CA083178/NH/NIH HHS/United States ; CA097397/NH/NIH HHS/United States ; CA114236/NH/NIH HHS/United States ; CA129639/NH/NIH HHS/United States ; },
}

@article {pmid39232161,
year = {2024},
author = {Zheng, XF and Sarkar, A and Lotana, H and Syed, A and Nguyen, H and Ivey, RG and Kennedy, JJ and Whiteaker, JR and Tomasik, B and Huang, K and Li, F and D'Andrea, AD and Paulovich, AG and Shah, K and Spektor, A and Chowdhury, D},
title = {CDK5-cyclin B1 regulates mitotic fidelity.},
journal = {Nature},
volume = {},
number = {},
pages = {},
pmid = {39232161},
issn = {1476-4687},
abstract = {CDK1 has been known to be the sole cyclin-dependent kinase (CDK) partner of cyclin B1 to drive mitotic progression[1]. Here we demonstrate that CDK5 is active during mitosis and is necessary for maintaining mitotic fidelity. CDK5 is an atypical CDK owing to its high expression in post-mitotic neurons and activation by non-cyclin proteins p35 and p39[2]. Here, using independent chemical genetic approaches, we specifically abrogated CDK5 activity during mitosis, and observed mitotic defects, nuclear atypia and substantial alterations in the mitotic phosphoproteome. Notably, cyclin B1 is a mitotic co-factor of CDK5. Computational modelling, comparison with experimentally derived structures of CDK-cyclin complexes and validation with mutational analysis indicate that CDK5-cyclin B1 can form a functional complex. Disruption of the CDK5-cyclin B1 complex phenocopies CDK5 abrogation in mitosis. Together, our results demonstrate that cyclin B1 partners with both CDK5 and CDK1, and CDK5-cyclin B1 functions as a canonical CDK-cyclin complex to ensure mitotic fidelity.},
}

@article {pmid39230981,
year = {2024},
author = {Collett, JA and Flannery, AH and Liu, LJ and Takeuchi, T and Basile, DP and Neyra, JA},
title = {IL-17A Levels and Progression of Kidney Disease Following Hospitalization with and without Acute Kidney Injury.},
journal = {Kidney360},
volume = {},
number = {},
pages = {},
doi = {10.34067/KID.0000000000000559},
pmid = {39230981},
issn = {2641-7650},
support = {R01DK063114/DK/NIDDK NIH HHS/United States ; U54DK137307/DK/NIDDK NIH HHS/United States ; K23DK128562/DK/NIDDK NIH HHS/United States ; R01DK063114/DK/NIDDK NIH HHS/United States ; U54DK137307/DK/NIDDK NIH HHS/United States ; K23DK128562/DK/NIDDK NIH HHS/United States ; },
abstract = {BACKGROUND: Acute kidney injury (AKI) is associated with increased mortality and new or progressive chronic kidney disease (CKD). Inflammatory cells play an important role in acute organ injury. We previously demonstrated that serum IL-17A levels were significantly elevated in critically ill patients with AKI and independently associated with hospital mortality. We hypothesize that IL-17A levels are elevated in hospitalized patients with AKI at diagnosis, and sustained elevation after discharge is associated with subsequent CKD incidence or progression.

METHODS: Observational convenience sampling study of hospital survivors of Stage 2 or 3 AKI and controls without AKI from the ASSESS-AKI study. Patients were classified as progression or non-progression based on a composite of CKD incidence, progression, or end-stage kidney disease. IL-17A levels were evaluated with S-Plex assay (MSD) at 0- (during hospitalization), 3- and 12-month post-discharge, and analyzed along with clinical and biomarker data up to 84 months following discharge.

RESULTS: Among 171 AKI and 175 non-AKI participants, IL-17A levels were elevated in AKI vs. non-AKI patients at 0M, 3M and 12M timepoints (p<0.05 for all comparisons). Further, IL-17A levels were elevated in the progression vs. non-progression group at the 3- and 12-month timepoints for outcomes occurring at 3-6 months and 12-84 months, respectively (p<0.05 for both). In adjusted multivariable models, IL-17A levels were not independently associated with progression of kidney disease. IL-17A levels were positively correlated with kidney disease and immune activation biomarkers at all timepoints (p<0.001).

CONCLUSIONS: IL-17A was higher in patients with AKI vs. without AKI during hospitalization and up to 1-year post-discharge. IL-17A was higher in patients with progression of kidney disease after hospitalization but not independently associated with subsequent progression of kidney disease in fully adjusted models.},
}

@article {pmid39229223,
year = {2024},
author = {Tisoncik-Go, J and Lewis, TB and Whitmore, LS and Voss, K and Niemeyer, S and Dai, J and Kim, P and Hubbell, K and Iwayama, N and Ahrens, C and Wangari, S and Murnane, R and Edlefsen, PT and Guerriero, KA and Gale, M and Fuller, DH and O'Connor, MA},
title = {Chronic innate immune impairment and ZIKV persistence in the gastrointestinal tract during SIV infection in pigtail macaques.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {39229223},
issn = {2692-8205},
support = {P51 OD010425/OD/NIH HHS/United States ; U19 AI113173/AI/NIAID NIH HHS/United States ; U42 OD011123/OD/NIH HHS/United States ; P30 AI027757/AI/NIAID NIH HHS/United States ; R01 AI145296/AI/NIAID NIH HHS/United States ; HHSN272201800003C/AI/NIAID NIH HHS/United States ; K01 MH123258/MH/NIMH NIH HHS/United States ; UL1 TR000423/TR/NCATS NIH HHS/United States ; },
abstract = {Mosquito borne flaviviruses, including dengue (DENV) and Zika (ZIKV) viruses, have caused global epidemics in areas with high HIV prevalence due to the expanded geographic range of arthropod vectors. Despite the occurrence of large flavivirus outbreaks in countries with high HIV prevalence, there is little knowledge regarding the effects of flavivirus infection in people living with HIV (PLWH). Here, we use a pigtail macaque model of HIV/AIDS to investigate the impact of simian immunodeficiency virus (SIV)-induced immunosuppression on ZIKV replication and pathogenesis. Early acute SIV infection induced expansion of peripheral ZIKV cellular targets and increased innate immune activation and peripheral blood mononuclear cells (PBMC) from SIV infected macaques were less permissive to ZIKV infection in vitro. In SIV-ZIKV co-infected animals, we found increased persistence of ZIKV in the periphery and tissues corresponding to alterations in innate cellular (monocytes, neutrophils) recruitment to the blood and tissues, decreased anti-ZIKV immunity, and chronic peripheral inflammatory and innate immune gene expression. Collectively, these findings suggest that untreated SIV infection may impair cellular innate responses and create an environment of chronic immune activation that promotes prolonged ZIKV viremia and persistence in the gastrointestinal tract. These results suggest that PLWH or other immunocompromised individuals could be at a higher risk for chronic ZIKV replication, which in turn could increase the timeframe of ZIKV transmission. Thus, PLWH are important populations to target during the deployment of vaccine and treatment strategies against ZIKV.},
}

@article {pmid39229127,
year = {2024},
author = {Kulsuptrakul, J and Emerman, M and Mitchell, PS},
title = {CARD8 inflammasome activation during HIV-1 cell-to-cell transmission.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {39229127},
issn = {2692-8205},
support = {DP1 DA051110/DA/NIDA NIH HHS/United States ; DP2 AI154432/AI/NIAID NIH HHS/United States ; T32 GM007270/GM/NIGMS NIH HHS/United States ; },
abstract = {Our previous work demonstrated that CARD8 detects HIV-1 infection by sensing the enzymatic activity of the HIV protease, resulting in CARD8-dependent inflammasome activation (Kulsuptrakul et al., 2023). CARD8 recognition of HIV-1 protease activity is conferred by a HIV protease substrate mimic within the CARD8 N-terminus, which when cleaved by HIV protease triggers CARD8 inflammasome activation. Here, we sought to understand CARD8 responses to HIV-1 when the virus is transmitted through cell-to-cell infection from infected cells to target cells via a viral synapse. We observed that cell-to-cell transmission of HIV-1 induces CARD8 inflammasome activation in immortalized cells and primary human monocyte-derived macrophages in a manner that is dependent on viral protease activity and largely independent of the NLRP3 inflammasome. Additionally, to further evaluate the viral determinants of CARD8 sensing, we tested a panel of HIV protease inhibitor resistant clones to establish how variation in HIV protease affects CARD8 activation. We identified mutant HIV-1 proteases that differentially cleave and activate CARD8 compared to wildtype HIV-1, thus indicating that natural variation in HIV protease affects not only the cleavage of the viral Gag-Pol polyprotein but also likely impacts innate sensing and inflammation.},
}

@article {pmid39229066,
year = {2024},
author = {Binkowski, B and Klamer, Z and Gao, C and Staal, B and Repesh, A and Tran, HL and Brass, DM and Bartlett, P and Gallinger, S and Blomqvist, M and Morrow, JB and Allen, P and Shi, C and Singhi, A and Brand, R and Huang, Y and Hostetter, G and Haab, BB},
title = {Multiplexed Glycan Immunofluorescence Identification of Pancreatic Cancer Cell Subpopulations in Both Tumor and Blood Samples.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {39229066},
issn = {2692-8205},
support = {U01 CA152653/CA/NCI NIH HHS/United States ; U01 CA200466/CA/NCI NIH HHS/United States ; U01 CA226158/CA/NCI NIH HHS/United States ; },
abstract = {Pancreatic ductal adenocarcinoma (PDAC) tumor heterogeneity impedes the development of biomarker assays suitable for early disease detection that would improve patient outcomes. The CA19-9 glycan is currently used as a standalone biomarker for PDAC. Furthermore, previous studies have shown that cancer cells may display aberrant membrane-associated glycans. We therefore hypothesized that PDAC cancer cell subpopulations could be distinguished by aberrant glycan signatures. We used multiplexed glycan immunofluorescence combined with pathologist annotation and automated image processing to distinguish between PDAC cancer cell subpopulations within tumor tissue. Using a training-set/test-set approach, we found that PDAC cancer cells may be identified by signatures comprising 4 aberrant glycans (VVL, CA19-9, sTRA, and GM2) and that there are three glycan-defined PDAC tumor types: sTRA type, CA19-9 type, and intermixed. To determine whether the aberrant glycan signatures could be detected in blood samples, we developed hybrid glycan sandwich assays for membrane-associated glycans. In both patient-matched tumor and blood samples, the proportion of aberrant glycans detected was consistent. Furthermore, our multiplexed glycan immunofluorescent approach proved to be more sensitive and more specific than CA19-9 alone. Our results provide proof of concept for a novel methodology to improve early PDAC detection and patient outcomes.},
}

@article {pmid39227162,
year = {2024},
author = {Tordoff, DM and Minalga, B and Catháin, NÓ and Fernandez, A and Gross, B and Glick, SN and , },
title = {Comparing Two-Step Approaches to Measuring Gender Identity: The Reliability and Applications of Asking About Sex Assigned at Birth versus Transgender Self-Identification.},
journal = {American journal of epidemiology},
volume = {},
number = {},
pages = {},
doi = {10.1093/aje/kwae341},
pmid = {39227162},
issn = {1476-6256},
abstract = {Inclusive measures of gender are critical for health equity research. This study compared the reliability and applications of two different approaches for measuring gender in response to emerging community concerns regarding the potential harms of asking about sex assigned at birth (SAAB) within transgender and gender diverse (TGD) populations. Using data from a 2021 survey of LGBTQ+ people in Washington state, we compared approaches for measuring gender via a two-step question that collected data on: (1) current gender and SAAB versus (2) current gender and transgender self-identification. Among 2,275 LGBTQ+ participants aged 9-81, 63% were cisgender, 35% TGD, and 2% were not categorized. There was near perfect agreement between the two methods in their ability to identify TGD participants (percent agreement=99.7%, unweighted Cohen's Kappa=0.99). Among gender diverse participants, stratification by SAAB revealed differences in sexual health outcomes, while stratification by transgender self-identification revealed differences in access to gender-affirming care and lifetime experiences of discrimination. Ascertaining SAAB may be most useful for identifying sexual health disparities while transgender self-identification may better illuminate healthcare needs and social determinants of health among TGD people. Researchers and public health practitioners should critically consider the acceptability and relevance of SAAB questions to their research goals.},
}

@article {pmid39226919,
year = {2024},
author = {Lin, W and Zou, J and Di, C and Rock, CL and Natarajan, L},
title = {Multilevel Longitudinal Functional Principal Component Model.},
journal = {Statistics in medicine},
volume = {},
number = {},
pages = {},
doi = {10.1002/sim.10207},
pmid = {39226919},
issn = {1097-0258},
support = {2100237//National Science Foundation/ ; 2120019//National Science Foundation/ ; R01HL130483//National Heart, Lung and Blood Institute/ ; PO1AG052352/AG/NIA NIH HHS/United States ; U54CA155435-01/CA/NCI NIH HHS/United States ; R01DK114945/DK/NIDDK NIH HHS/United States ; },
abstract = {Sensor devices, such as accelerometers, are widely used for measuring physical activity (PA). These devices provide outputs at fine granularity (e.g., 10-100 Hz or minute-level), which while providing rich data on activity patterns, also pose computational challenges with multilevel densely sampled data, resulting in PA records that are measured continuously across multiple days and visits. On the other hand, a scalar health outcome (e.g., BMI) is usually observed only at the individual or visit level. This leads to a discrepancy in numbers of nested levels between the predictors (PA) and outcomes, raising analytic challenges. To address this issue, we proposed a multilevel longitudinal functional principal component analysis (mLFPCA) model to directly model multilevel functional PA inputs in a longitudinal study, and then implemented a longitudinal functional principal component regression (FPCR) to explore the association between PA and obesity-related health outcomes. Additionally, we conducted a comprehensive simulation study to examine the impact of imbalanced multilevel data on both mLFPCA and FPCR performance and offer guidelines for selecting optimal methods.},
}

@article {pmid39226462,
year = {2024},
author = {Huffman, JE and Nicholas, J and Hahn, J and Heath, AS and Raffield, LM and Yanek, LR and Brody, JA and Thibord, F and Almasy, L and Bartz, TM and Bielak, LF and Bowler, RP and Carrasquilla, GD and Chasman, DI and Chen, MH and Emmert, DB and Ghanbari, M and Haessler, J and Hottenga, JJ and Kleber, ME and Le, NQ and Lee, J and Lewis, JP and Li-Gao, R and Luan, J and Malmberg, AL and Mangino, M and Marioni, R and Martinez-Perez, A and Pankratz, N and Polasek, O and Richmond, A and Rodriguez, BAT and Rotter, JI and Steri, M and Suchon, P and Trompet, S and Weiss, S and Zare, M and Auer, PL and Cho, M and Christofidou, P and Davies, G and de Geus, EJ and Deleuze, JF and Delgado, GE and Ekunwe, L and Faraday, N and Gogele, M and Greinacher, A and Gao, H and Howard, TE and Joshi, PK and Kilpeläinen, TO and Lahti, J and Linneberg, A and Naitza, S and Noordam, R and Vergés, FP and Rich, SS and Rosendaal, FR and Rudan, I and Ryan, KA and Souto, JCC and van Rooij, FJA and Wang, H and Zhao, W and Becker, L and Beswick, A and Brown, MR and Cade, B and Campbell, H and Cho, K and Crapo, J and Curran, J and de Maat, MPM and Doyle, MF and Elliott, P and Floyd, JS and Fuchsberger, C and Grarup, N and Guo, X and Harris, S and Hou, L and Kolcic, I and Kooperberg, C and Menni, C and Nauck, M and O'Connell, JR and Orru, V and Psaty, BM and Räikkönen, K and Smith, JA and Soria, JM and Stott, D and van Hylckama Vlieg, A and Watkins, H and Willemsen, G and Wilson, PW and Ben-Shlomo, Y and Blangero, J and Boomsma, D and Cox, SR and Dehghan, A and Eriksson, JG and Fiorillo, E and Fornage, M and Hansen, T and Hayward, C and Ikram, MA and Jukema, JW and Kardia, S and Lange, L and Maerz, W and Mathias, R and Mitchell, BD and Mook-Kanamori, DO and Morange, PE and Pedersen, O and Pramstaller, PP and Redline, S and Reiner, AP and Ridker, PM and Silverman, EK and Spector, TD and Volker, U and Wareham, N and Wilson, J and Yao, J and Tregouet, DA and Johnson, AD and Wolberg, AS and de Vries, PS and Sabater-Lleal, M and Morrison, A and Smith, NL},
title = {Whole-genome analysis of plasma fibrinogen reveals population-differentiated genetic regulators with putative liver roles.},
journal = {Blood},
volume = {},
number = {},
pages = {},
doi = {10.1182/blood.2023022596},
pmid = {39226462},
issn = {1528-0020},
abstract = {Genetic studies have identified numerous regions associated with plasma fibrinogen levels in Europeans, yet missing heritability and limited inclusion of non-Europeans necessitates further studies with improved power and sensitivity. Compared with array-based genotyping, whole genome sequencing (WGS) data provides better coverage of the genome and better representation of non-European variants. To better understand the genetic landscape regulating plasma fibrinogen levels, we meta-analyzed WGS data from the NHLBI's Trans-Omics for Precision Medicine (TOPMed) program (n=32,572), with array-based genotype data from the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium (n=131,340) imputed to the TOPMed or Haplotype Reference Consortium panel. We identified 18 loci that have not been identified in prior genetic studies of fibrinogen. Of these, four are driven by common variants of small effect with reported MAF at least 10 percentage points higher in African populations. Three signals (SERPINA1, ZFP36L2, and TLR10) contain predicted deleterious missense variants. Two loci, SOCS3 and HPN, each harbor two conditionally distinct, non-coding variants. The gene region encoding the fibrinogen protein chain subunits (FGG;FGB;FGA), contains 7 distinct signals, including one novel signal driven by rs28577061, a variant common in African ancestry populations but extremely rare in Europeans (MAFAFR=0.180; MAFEUR=0.008). Through phenome-wide association studies in the VA Million Veteran Program, we found associations between fibrinogen polygenic risk scores and thrombotic and inflammatory disease phenotypes, including an association with gout. Our findings demonstrate the utility of WGS to augment genetic discovery in diverse populations and offer new insights for putative mechanisms of fibrinogen regulation.},
}

@article {pmid39226323,
year = {2024},
author = {Wang, K and Jordan, T and Dowdell, K and Herbert, R and Moore, IN and Koelle, DM and Cohen, JI},
title = {A nonhuman primate model for genital herpes simplex virus 2 infection that results in vaginal vesicular lesions, virus shedding, and seroconversion.},
journal = {PLoS pathogens},
volume = {20},
number = {9},
pages = {e1012477},
pmid = {39226323},
issn = {1553-7374},
mesh = {Animals ; *Herpes Genitalis/immunology/virology ; Female ; *Herpesvirus 2, Human/immunology ; *Virus Shedding/immunology ; *Disease Models, Animal ; *Seroconversion ; Antibodies, Viral/immunology ; Vagina/virology/immunology/pathology ; Macaca mulatta ; },
abstract = {The most commonly used animal models for evaluating the efficacy of HSV-2 candidate vaccines are mice and guinea pigs. While numerous HSV-2 vaccine candidates have been tested in these animals and were effective in reducing disease and mortality, these results did not predict the effectiveness of the vaccines in human trials. Infection of rhesus macaques rarely results in lesions or HSV-2 specific antibody responses. In seeking an animal model that better recapitulates human disease and that might be more predictive of the efficacy of prophylactic vaccines than mice and guinea pigs, we evaluated Cebus apella (C. apella), a New World primate, in an HSV-2 genital infection model. Infectious HSV-2 was cultured from vaginal swabs from all 4 animals for 9-14 days after intravaginal inoculation of HSV-2 seronegative monkeys. Two of 4 monkeys had vesicular lesions in the vagina or vulva. No neurological symptoms were noted. Recurrent lesions and HSV-2 DNA shedding after acute disease resolved was infrequent. UV irradiation of the genital area did not induce recurrent genital lesions or virus shedding. All 4 monkeys developed HSV-2 neutralizing antibodies as well as virus-specific CD4 and CD8 T cell responses. Reinfection of animals 15 to 19 months after primary infection did not result in lesions; animals had reduced virus shedding and a shorter duration of shedding compared with that during primary infection, suggesting that primary infection induced protective immunity. Primary fibroblasts from C. apella monkeys supported the growth of HSV-2 in vitro; in contrast, HSV-2 did not replicate above the titer of the input inoculum in fibroblasts from rhesus macaques. These observations suggest that the C. apella monkey has potential to serve as a model for evaluating the efficacy of prophylactic vaccines, antivirals, or monoclonal antibodies to HSV-2.},
}

Animals
*Herpes Genitalis/immunology/virology
Female
*Herpesvirus 2, Human/immunology
*Virus Shedding/immunology
*Disease Models, Animal
*Seroconversion
Antibodies, Viral/immunology
Vagina/virology/immunology/pathology
Macaca mulatta

@article {pmid39225478,
year = {2024},
author = {Janes, H and Fisher, LH and Kee, JJ and Parameswaran, L and Goepfert, PA and Falsey, AR and Ludwig, J and Magaret, CA and Gilbert, PB and Kublin, JG and Rouphael, N and Sobieszczyk, ME and El Sahly, HM and Baden, LR and Grinsztejn, B and Walsh, SR and Gray, GE and Kotloff, KL and Gay, CL and Greninger, AL and Tapia, MD and Hammershaimb, EA and Priddy, FH and Green, JA and Struyf, F and Dunkle, L and Neuzil, KM and Corey, L and Huang, Y},
title = {Association Between SARS-CoV-2 Viral Load and COVID-19 Vaccination in 4 Phase 3 Trials.},
journal = {The Journal of infectious diseases},
volume = {},
number = {},
pages = {},
doi = {10.1093/infdis/jiae400},
pmid = {39225478},
issn = {1537-6613},
support = {//United States Government/ ; //Biomedical Advanced Research/ ; //and Development Authority/ ; UM1 AI068614/AI/NIAID NIH HHS/United States ; },
abstract = {Coronavirus disease 2019 (COVID-19) vaccines reduce severe disease and mortality and may lessen transmission, measured by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral load (VL). Evaluating vaccine associations in VL at COVID-19 diagnosis in 4 phase 3 randomized, placebo-controlled vaccine trials, July 2020 to July 2021, VL reductions were 2.78 log10 copies/mL (95% confidence interval [CI], 1.38-4.18; n = 60 placebo, 11 vaccine) and 2.12 log10 copies/mL (95% CI, 1.44-2.80; n = 594 placebo, 36 vaccine) for NVX-CoV2373 and mRNA-1273, respectively. Associations were not significant for AZD1222 (0.59 log10 copies/mL; 95% CI, -.19 to 1.36; n = 90 placebo, 78 vaccine) or Ad26.COV2.S (0.23 log10 copies/mL; 95% CI, -.01 to .47; n = 916 placebo, 424 vaccine). Thus, vaccines potentially decreased transmission when ancestral SARS-CoV-2 predominated. Clinical Trials Registration. NCT04470427, NCT04505722, NCT04516746, NCT04611802.},
}

@article {pmid39225130,
year = {2024},
author = {Wang, Y and Scurll, J and Rascón, IA and Cui, C and Ni, Y and Shi, AM and Gangadharannambiar, P and Wang, Y and Akamatsu, S and Beltran, H and Cox, M and Crea, F and Daugaard, M and Dong, X and Haffner, M and He, H and Jachetti, E and Kyprianou, N and Li, B and Ong, CE and Rickman, DS and Sen, T and Zhu, HH and Zoubeidi, A and Gleave, ME},
title = {The third symposium on treatment-induced neuroendocrine prostate cancer: insights and future directions.},
journal = {Epigenomics},
volume = {},
number = {},
pages = {1-4},
doi = {10.1080/17501911.2024.2391729},
pmid = {39225130},
issn = {1750-192X},
abstract = {Neuroendocrine prostate cancer (NEPC) is a rare and aggressive subtype of prostate cancer (PCa), emerging from advanced treatments and characterized by loss of androgen receptor (AR) signaling and neuroendocrine features, leading to rapid progression and treatment resistance. The third symposium on treatment-induced NEPC, held from 21 to 23 June 2024, at Harrison Hot Springs Resort, BC, Canada, united leading global researchers and clinicians. Sponsored by the Vancouver Prostate Centre (VPC), Canadian Institute of Health Research, Prostate Cancer Foundation Canada and Pharma Planter Inc, the event focused on the latest NEPC research and innovative treatment strategies. Co-chaired by Drs. Yuzhuo Wang and Martin Gleave, the symposium featured sessions on NEPC's historical context, molecular pathways, epigenetic regulation and the role of the tumor microenvironment and metabolism in its progression. Keynotes from experts like Dr. Himisha Beltran and Dr. Martin Gleave highlighted the complexity of NEPC. The Emerging Talent session showcased new research, pointing to the future of NEPC treatment. The symposium concluded with a consensus on the need for early detection, targeted therapies and personalized medicine to effectively combat NEPC, emphasizing the importance of global collaboration in advancing NEPC understanding and treatment.},
}

@article {pmid39224838,
year = {2024},
author = {Zhao, Y and Jia, Q and Goodrich, J and Darst, B and Conti, DV},
title = {An extension of latent unknown clustering integrating multi-omics data (LUCID) incorporating incomplete omics data.},
journal = {Bioinformatics advances},
volume = {4},
number = {1},
pages = {vbae123},
pmid = {39224838},
issn = {2635-0041},
abstract = {MOTIVATION: Latent unknown clustering integrating multi-omics data is a novel statistical model designed for multi-omics data analysis. It integrates omics data with exposures and an outcome through a latent cluster, elucidating how exposures influence processes reflected in multi-omics measurements, ultimately affecting an outcome. A significant challenge in multi-omics analysis is the issue of list-wise missingness. To address this, we extend the model to incorporate list-wise missingness within an integrated imputation framework, which can also handle sporadic missingness when necessary.

RESULTS: Simulation studies demonstrate that our integrated imputation approach produces consistent and less biased estimates, closely reflecting true underlying values. We applied this model to data from the ISGlobal/ATHLETE "Exposome Data Challenge Event" to explore the association between maternal exposure to hexachlorobenzene and childhood body mass index by integrating incomplete proteomics data from 1301 children. The model successfully estimated proteomics profiles for two clusters representing higher and lower body mass index, characterizing the potential profiles linking prenatal hexachlorobenzene levels and childhood body mass index.

The proposed methods have been implemented in the R package LUCIDus. The source code is available at https://github.com/USCbiostats/LUCIDus.},
}

@article {pmid39224504,
year = {2024},
author = {Fiorenza, S and Lim, SYT and Laszlo, GS and Kimble, EL and Phi, TD and Lunn-Halbert, MC and Kirchmeier, DR and Huo, J and Kiem, HP and Turtle, CJ and Walter, RB},
title = {Targeting the membrane-proximal C2-set domain of CD33 for improved CAR T cell therapy.},
journal = {Molecular therapy. Oncology},
volume = {32},
number = {3},
pages = {200854},
pmid = {39224504},
issn = {2950-3299},
abstract = {Current CD33-targeted immunotherapies typically recognize the membrane-distal V-set domain of CD33. Here, we show that decreasing the distance between T cell and leukemia cell membrane increases the efficacy of CD33 chimeric antigen receptor (CAR) T cells. We therefore generated and optimized second-generation CAR constructs containing single-chain variable fragments from antibodies raised against the membrane-proximal C2-set domain, which bind CD33 regardless of whether the V-set domain is present (CD33[PAN] antibodies). CD33[PAN] CAR T cells resulted in efficient tumor clearance and improved survival of immunodeficient mice bearing human AML cell xenografts and, in an AML model with limited CD33 expression, forced escape of CD33[neg] leukemia. Compared to CD33[V-set] CAR T cells, CD33[PAN] CAR T cells showed greater in vitro and in vivo efficacy against several human AML cell lines with differing levels of CD33 without increased expression of exhaustion markers. CD33[PAN] moieties were detected at a higher frequency on human leukemic stem cells, and CD33[PAN] CAR T cells had greater in vitro efficacy against primary human AML cells. Together, our studies demonstrate improved efficacy with CAR T cells binding CD33 close to the cell membrane, providing the rationale to investigate CD33[PAN] CAR T cells further toward possible clinical application.},
}

@article {pmid39223980,
year = {2024},
author = {Zheng, Y and Wagner, PD and Singal, AG and Hanash, SM and Srivastava, S and Huang, Y and Zhao, YQ and Chari, ST and Marquez, G and Etizioni, R and Marsh, TL and Feng, Z},
title = {Designing Rigorous and Efficient Clinical Utility Studies for Early Detection Biomarkers.},
journal = {Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology},
volume = {33},
number = {9},
pages = {1150-1157},
doi = {10.1158/1055-9965.EPI-23-1594},
pmid = {39223980},
issn = {1538-7755},
mesh = {Humans ; *Biomarkers, Tumor/blood/analysis ; *Early Detection of Cancer/methods ; *Research Design ; *Neoplasms/diagnosis ; },
abstract = {Before implementing a biomarker in routine clinical care, it must demonstrate clinical utility by leading to clinical actions that positively affect patient-relevant outcomes. Randomly controlled early detection utility trials, especially those targeting mortality endpoint, are challenging due to their high costs and prolonged duration. Special design considerations are required to determine the clinical utility of early detection assays. This commentary reports on discussions among the National Cancer Institute's Early Detection Research Network investigators, outlining the recommended process for carrying out single-organ biomarker-driven clinical utility studies. We present the early detection utility studies in the context of phased biomarker development. We describe aspects of the studies related to the features of biomarker tests, the clinical context of endpoints, the performance criteria for later phase evaluation, and study size. We discuss novel adaptive design approaches for improving the efficiency and practicality of clinical utility trials. We recommend using multiple strategies, including adopting real-world evidence, emulated trials, and mathematical modeling to circumvent the challenges in conducting early detection utility trials.},
}

Humans
*Biomarkers, Tumor/blood/analysis
*Early Detection of Cancer/methods
*Research Design
*Neoplasms/diagnosis

@article {pmid39222529,
year = {2024},
author = {Naresh, KN},
title = {Classification of Haematolymphoid Neoplasms: A work in progress towards more precise disease definitions in the era of precision oncology.},
journal = {The National medical journal of India},
volume = {37},
number = {2},
pages = {61-63},
doi = {10.25259/NMJI_918_2024},
pmid = {39222529},
issn = {2583-150X},
mesh = {Humans ; *Precision Medicine ; Hematologic Neoplasms/classification/diagnosis/therapy ; Medical Oncology/standards/trends ; },
}

Humans
*Precision Medicine
Hematologic Neoplasms/classification/diagnosis/therapy
Medical Oncology/standards/trends

@article {pmid39221247,
year = {2024},
author = {Arias-Badia, M and Pai, CS and Chen, P and Chang, A and Lwin, YM and Srinath, A and Gotts, JE and Glantz, SA and Fong, L},
title = {E-cigarette exposure disrupts antitumor immunity and promotes metastasis.},
journal = {Frontiers in immunology},
volume = {15},
number = {},
pages = {1444020},
pmid = {39221247},
issn = {1664-3224},
mesh = {Animals ; *Electronic Nicotine Delivery Systems ; Mice ; *Nicotine ; Neoplasm Metastasis ; Mice, Inbred C57BL ; Cell Line, Tumor ; CTLA-4 Antigen/immunology ; Female ; Cell Movement/drug effects ; Programmed Cell Death 1 Receptor ; },
abstract = {Electronic cigarettes (e-cigarettes) are thought to pose low risk of cancer because the components of e-cigarette liquid are not carcinogens. We analyzed the effects of the two major components, PG/VG and nicotine, on tumor development in preclinical models. We found that PG/VG promoted tumor cell migration in migration assays and contributed to more aggressive, metastatic, and immunosuppressive tumors in vivo, aggravated by the presence of nicotine. Whole body exposure of mice to PG/VG and nicotine rendered animals more susceptible to developing tumors with high frequencies of infiltrating proinflammatory macrophages expressing IL-6 and TNFα. Moreover, tumor-infiltrating and circulating T cells in e-cigarette exposed mice showed increased levels of immune checkpoints including CTLA4 and PD-1. Treatment with anti-CTLA4 antibody was able to abrogate metastasis with no detrimental effects on its ability to induce tumor regression in exposed mice. These findings suggest that the major components used in e-cigarette fluid can impact tumor development through induced immunosuppression.},
}

Animals
*Electronic Nicotine Delivery Systems
Mice
*Nicotine
Neoplasm Metastasis
Mice, Inbred C57BL
Cell Line, Tumor
CTLA-4 Antigen/immunology
Female
Cell Movement/drug effects
Programmed Cell Death 1 Receptor

@article {pmid39221180,
year = {2024},
author = {Rader, NA and Lee, KS and Loes, AN and Miller-Stump, OA and Cooper, M and Wong, TY and Boehm, DT and Barbier, M and Bevere, JR and Heath Damron, F},
title = {Influenza virus strains expressing SARS-CoV-2 receptor binding domain protein confer immunity in K18-hACE2 mice.},
journal = {Vaccine: X},
volume = {20},
number = {},
pages = {100543},
pmid = {39221180},
issn = {2590-1362},
abstract = {Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease (COVID-19), rapidly spread across the globe in 2019. With the emergence of the Omicron variant, COVID-19 shifted into an endemic phase. Given the anticipated rise in cases during the fall and winter seasons, the strategy of implementing seasonal booster vaccines for COVID-19 is becoming increasingly valuable to protect public health. This practice already exists for seasonal influenza vaccines to combat annual influenza seasons. Our goal was to investigate an easily modifiable vaccine platform for seasonal use against SARS-CoV-2. In this study, we evaluated the genetically modified influenza virus ΔNA(RBD) as an intranasal vaccine candidate for COVID-19. This modified virus was engineered to replace the coding sequence for the neuraminidase (NA) protein with a membrane-anchored form of the receptor binding domain (RBD) protein of SARS-CoV-2. We designed experiments to assess the protection of ΔNA(RBD) in K18-hACE2 mice using lethal (Delta) and non-lethal (Omicron) challenge models. Controls of COVID-19 mRNA vaccine and our lab's previously described intranasal virus like particle vaccine were used as comparisons. Immunization with ΔNA(RBD) expressing ancestral RBD elicited high anti-RBD IgG levels in the serum of mice, high anti-RBD IgA in lung tissue, and improved survival after Delta variant challenge. Modifying ΔNA(RBD) to express Omicron variant RBD shifted variant-specific antibody responses and limited viral burden in the lungs of mice after Omicron variant challenge. Overall, this data suggests that ΔNA(RBD) could be an effective intranasal vaccine platform that generates mucosal and systemic immunity towards SARS-CoV-2.},
}

@article {pmid39219850,
year = {2024},
author = {Alvarez, L and April-Sanders, A and Duran Luciano, P and Lee, UJ and Swett, K and Herrera, C and Collado, D and Kaplan, R and Gonzalez Ii, F and Daviglus, M and Garcia-Bedoya, O and Elfassy, T and Schneiderman, N and Perreira, K and Talavera, GA and Corsino, L and Rodriguez, CJ},
title = {Hypertension Prevalence among Hispanics/Latinos of Dominican Background: A Transnational Comparison of HCHS/SOL and ENPREFAR-HAS-17.},
journal = {Global heart},
volume = {19},
number = {1},
pages = {71},
pmid = {39219850},
issn = {2211-8179},
mesh = {Humans ; Male ; Female ; *Hypertension/epidemiology/ethnology ; Prevalence ; *Hispanic or Latino/statistics & numerical data ; Adult ; Dominican Republic/ethnology/epidemiology ; Middle Aged ; United States/epidemiology ; Risk Factors ; Cross-Sectional Studies ; },
abstract = {BACKGROUND: Hispanics/Latinos of Dominican background living in United States (US) have the highest hypertension prevalence compared with other Hispanic/Latino persons.

OBJECTIVE: To understand cardiovascular health among Dominicans, we evaluated hypertension prevalence and risk factors among Dominicans from the US and Dominican Republic (DR) using data from Hispanic Community Health Study/ Study of Latinos [HCHS/SOL] and the Prevalencia de Hipertension Arterial y Factores de Riesgo Cardiovasculares en la República Dominicana al 2017 (ENPREFAR-HAS 17) study.

METHODS: Hypertension was defined as blood pressure ≥140/90 mmHg, self-reported hypertension, or antihypertensive use. Exposures included sociodemographic/socioeconomic, clinical, and lifestyle/behavioral characteristics. Weighted generalized linear models were used to estimate associations between study characteristics and hypertension prevalence (PR = prevalence ratio), age-and-sex adjusted. HCHS/SOL (n = 1,473, US Dominicans; mean age 41 years, 60.4% female) was analyzed with survey procedures, while ENPREFAR-HAS 17 (n = 2,015 DR Dominicans; mean age 40 years, 50.3% female) was analyzed with statistical analyses for simple random sampling.

RESULTS: Hypertension prevalence was 30.5% and 26.9% for DR and US Dominicans, respectively. Hypertension control was low in both cohorts (36.0% DR, 35.0% US). Alcohol use among DR Dominicans was inversely associated with hypertension prevalence (PRDR = 0.8) with no association among US Dominicans. In both settings, diabetes (PRDR = 1.4; PRUS = 1.4) and obesity (PRDR = 1.8; PRUS = 2.0) were associated with greater hypertension prevalence in Hispanics/Latinos of Dominican background. Physical activity was lower among US Dominicans (PR = 0.80) but higher among DR Dominicans (PR = 1.16); all p < 0.05.

CONCLUSIONS: Variations in social, lifestyle/behavioral, and clinical characteristics associated with hypertension among Dominicans in the US and DR were identified, suggesting that social context and cultural factors matter among immigrant populations.},
}

Humans
Male
Female
*Hypertension/epidemiology/ethnology
Prevalence
*Hispanic or Latino/statistics & numerical data
Adult
Dominican Republic/ethnology/epidemiology
Middle Aged
United States/epidemiology
Risk Factors
Cross-Sectional Studies

@article {pmid39219510,
year = {2023},
author = {Thomas, LD and Batarseh, E and Hamdan, L and Haddadin, Z and Dulek, D and Kalams, S and Stewart, LS and Stahl, AL and Rahman, H and Amarin, JZ and Hayek, H and Ison, M and Overton, ET and Pergam, SA and Spieker, AJ and Halasa, NB and , },
title = {Comparison of Two High-Dose Versus Two Standard-Dose Influenza Vaccines in Adult Allogeneic Hematopoietic Cell Transplant Recipients.},
journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America},
volume = {77},
number = {12},
pages = {1723-1732},
pmid = {39219510},
issn = {1537-6591},
support = {//NIH/ ; },
mesh = {Humans ; *Influenza Vaccines/administration & dosage/immunology ; *Hematopoietic Stem Cell Transplantation ; Male ; Middle Aged ; Female ; Adult ; *Influenza, Human/prevention & control/immunology ; Double-Blind Method ; *Antibodies, Viral/blood ; Young Adult ; Aged ; Transplant Recipients ; Influenza A Virus, H3N2 Subtype/immunology ; Hemagglutination Inhibition Tests ; Influenza A Virus, H1N1 Subtype/immunology ; Transplantation, Homologous ; Vaccination/methods ; Influenza B virus/immunology ; Immunogenicity, Vaccine ; },
abstract = {BACKGROUND: Adult hematopoietic cell transplant (HCT) recipients are at high risk for influenza-related morbidity and mortality and have suboptimal influenza vaccine immune responses compared to healthy adults, particularly within 2 years of transplant.

METHODS: This phase II, double-blind, multicenter randomized controlled trial compared 2 doses of high-dose trivalent (HD-TIV) to 2 doses of standard-dose quadrivalent (SD-QIV) influenza vaccine administered 1 month apart in adults 3-23 months post-allogeneic HCT. Hemagglutinin antibody inhibition (HAI) titers were measured at baseline, 4 weeks following each vaccine dose, and approximately 7 months post-second vaccination. Injection-site and systemic reactions were assessed for 7 days post-vaccination. The primary immunogenicity comparison was geometric mean HAI titer (GMT) at visit 3 (4 weeks after the second dose); we used linear mixed models to estimate adjusted GMT ratios (aGMRs) comparing HD-TIV/SD-QIV for each antigen.

RESULTS: We randomized 124 adults; 64 received SD-QIV and 60 received HD-TIV. Following the second vaccination, HD-TIV was associated with higher GMTs compared to SD-QIV for A/H3N2 (aGMR = 2.09; 95% confidence interval [CI]: [1.19, 3.68]) and B/Victoria (aGMR = 1.61; 95% CI: [1.00, 2.58]). The increase was not statistically significant for A/H1N1 (aGMR = 1.16; 95% CI: [0.67, 2.02]). There was a trend to more injection-site reactions for HD-TIV after the second vaccination compared to SD-QIV (50% vs 33%; adjusted odds ratio [aOR] = 4.53; 95% CI: [0.71, 28.9]), whereas systemic reactions were similar between groups with both injections.

CONCLUSIONS: Adult allogeneic HCT recipients who received 2 doses of HD-TIV produced higher HAI antibody responses for A/H3N2 and B/Victoria compared with 2 doses of SD-QIV, with comparable injection-site or systemic reactions.},
}

Humans
*Influenza Vaccines/administration & dosage/immunology
*Hematopoietic Stem Cell Transplantation
Male
Middle Aged
Female
Adult
*Influenza, Human/prevention & control/immunology
Double-Blind Method
*Antibodies, Viral/blood
Young Adult
Aged
Transplant Recipients
Influenza A Virus, H3N2 Subtype/immunology
Hemagglutination Inhibition Tests
Influenza A Virus, H1N1 Subtype/immunology
Transplantation, Homologous
Vaccination/methods
Influenza B virus/immunology
Immunogenicity, Vaccine

@article {pmid39219377,
year = {2024},
author = {Petersen, E and Cavanaugh, D and Psutka, SP},
title = {Current developments in prehabilitation in urologic oncology.},
journal = {Current opinion in urology},
volume = {},
number = {},
pages = {},
doi = {10.1097/MOU.0000000000001224},
pmid = {39219377},
issn = {1473-6586},
abstract = {PURPOSE OF REVIEW: Prehabilitation describes interventions that are undertaken prior to a major surgical or medical intervention with the objective of improving functional capability with the goal of improving candidacy for therapy, bolstering one's ability to withstand treatment-associated toxicity, functional decline, and facilitating accelerated recovery. The objective of this review is to detail the key tenets of prehabilitation, synthesize contemporary advances in prehabilitation science within Urologic Oncology, and discuss key methodologic trial design considerations salient to future prehabilitation investigations.

RECENT FINDINGS: Contemporary prehabilitation clinical trials have primarily evaluated unimodal interventions aiming to improve functional capacity across the domains of physical exercise, nutrition, and cognition with heightened interest in evaluating multimodal interventions addressing two or more domains. Recent investigations have have demonstrated variable improvements in strength, balance, physical function, and quality of life with preoperative exercise. Although presurgical immunonutrition showed promise in other fields, initial results in uro-oncology have not demonstrated reductions in complications nor improvements in early survival. Emerging data supports the potential of multimodal prehabilitation programs to offer more comprehensive benefits, improving functional outcomes, reducing length of stay, and supporting improved recovery.

SUMMARY: To date, early prehabilitation studies in patients undergoing surgery for genitourinary malignancies have demonstrated variable ability to facilitate gains in functional capacity and perioperative outcomes. Key issues have arisen including the need to ensure that interventions are pragmatic, scalable, feasible, and acceptable in these populations that often also have a high prevalence of coincident multimorbidity, frailty, and mental health concerns that can increase risk of adverse outcomes after surgery. The integration of personalized prehabilitation strategies as extensions of perioperative enhanced recovery after surgery protocols, supportive care and survivorship paradigms offers of promise to further engage patients in their care, enhance patient resilience and outcomes, while reducing treatment burden in urologic oncology.},
}

@article {pmid39218742,
year = {2024},
author = {Contieri, R and Soloway, MS and Gontero, P and Herr, H and Kassouf, W and Mertens, LS and Moschini, M and O'Donnell, M and Palou, J and Psutka, SP and Rouprêt, M and Teoh, JYC and Kamat, AM},
title = {Deintensification of Treatment for Low-grade Bladder Tumors: A Collaborative Review by the International Bladder Cancer Group (IBCG).},
journal = {European urology oncology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.euo.2024.08.001},
pmid = {39218742},
issn = {2588-9311},
abstract = {BACKGROUND AND OBJECTIVE: Management of low-grade (LG) urothelium-confined (Ta stage) non-muscle-invasive bladder cancer (NMIBC) poses a distinct therapeutic challenge. Transurethral resection of bladder tumor (TURBT), the standard treatment, frequently has to be repeated because of high tumor recurrence rates. This places a considerable strain on both patients and health care infrastructure, underscoring the need for alternative management approaches. Herein, the IBCG (International Bladder Cancer Group), conducted a review to explore the efficacy and safety of deintensified treatment strategies for recurrent LG Ta NMIBC.

METHODS: We conducted a collaborative review of relevant literature in the PubMed/MEDLINE and Cochrane CENTRAL databases. Our focus was on high-quality evidence, including randomized controlled trials, systematic reviews, and meta-analyses. We also reviewed guidelines published by prominent urological associations.

KEY FINDINGS AND LIMITATIONS: Active surveillance, chemoablation, and office fulguration are valid treatment options for recurrent LG Ta NMIBC. These deintensified approaches offer several advantages over TURBT: lower complication rates, less morbidity, lower health care costs, and better quality of life for patients. Importantly, these benefits are achieved without compromising oncological safety.

Our review demonstrates that less intensive treatment strategies for recurrent LG Ta NMIBC are both feasible and valuable. The IBCG recommends use of these approaches for carefully selected patients to help lower health care costs and enhance patients' quality of life.

PATIENT SUMMARY: We reviewed studies on less invasive management options for low-grade noninvasive bladder cancer, including active surveillance, chemical ablation, and heat treatment. Recent results confirm that these less intense treatment options can reduce the treatment burden and costs for patients and preserve their quality of life without negatively affecting cancer control outcomes.},
}

@article {pmid39218309,
year = {2024},
author = {Aziz, AB and Sugimoto, JD and Hong, SL and You, YA and Bravo, L and Roa, C and Borja-Tabora, C and Montellano, MEB and Carlos, J and de Los Reyes, MRA and Alberto, ER and Salvani-Bautista, M and Kim, HY and Njau, I and Clemens, R and Marks, F and Tadesse, BT},
title = {Indirect effectiveness of a novel SAR-COV-2 vaccine (SCB-2019) in unvaccinated household contacts in the Philippines: A cluster randomised analysis.},
journal = {The Journal of infection},
volume = {89},
number = {4},
pages = {106260},
doi = {10.1016/j.jinf.2024.106260},
pmid = {39218309},
issn = {1532-2742},
abstract = {BACKGROUND: Though observational evidence supports indirect effects of SARS-CoV-2 vaccines, randomised experiments are lacking. To address this gap, the double-blinded, prospective follow-up of the household contacts (HHCs) of Philippine participants of the individually-randomised, placebo-controlled trial of the adjuvanted-subunit protein COVID-19 vaccine, SCB-2019, (EudraCT, 2020-004272-17; ClinicalTrials.gov, NCT04672395) was analyzed in a cluster-randomised fashion.

METHODS: Over an eight-week period, HHCs were followed by rRT-PCR and paired rapid antibody tests (RATs) to detect symptomatic (SCI, primary) and all (ACI, secondary) SARS-CoV-2 infection. A standard analysis estimated the indirect effectiveness of SCB-2019 for each endpoint, excluding HHC RAT-positive at enrollment. A secondary analysis employed enzyme-linked immunosorbent assay (ELISA) results to correct for suspected bias.

FINDINGS: SCB-2019 (N = 3470) and placebo (N = 3225) exposed HHCs contributed to at least one analysis. The standard analysis estimated that SCB-2019 reduced the risk of SCI by 83% (95% confidence/credible interval [CI: 32% to 96%), with no effect against ACI. The bias-corrected relative risk reduction was 97% (95% CI: 74% to 100%) for SCI and 79% (95% CI: 14% to 96%) for ACI, with an estimated one SARS-CoV-2 infection prevented per 4.8 households where one member received SCB-2019.

INTERPRETATION: SCB-2019 demonstrated bias-corrected indirect effectiveness against SARS-CoV-2 infection among HHC, even at a modest coverage level in the household (approximately 25%). Further research into the indirect effects of SARS-CoV-2 vaccines is needed to optimize the impact of limited doses in low and middle-income settings.},
}

@article {pmid39217999,
year = {2024},
author = {Kahn, J and Brazauskas, R and Bo-Subait, S and Buchbinder, D and Hamilton, BK and Schoemans, H and Abraham, AA and Agrawal, V and Auletta, JJ and Badawy, SM and Beitinjaneh, A and Bhatt, NS and Broglie, L and Diaz Perez, MA and Farhadfar, N and Freytes, CO and Gale, RP and Ganguly, S and Hayashi, RJ and Hematti, P and Hildebrandt, GC and Inamoto, Y and Kamble, RT and Koo, J and Lazarus, HM and Mayo, SJ and Mehta, PA and Myers, KC and Nishihori, T and Prestidge, T and Rotz, SJ and Savani, BN and Schears, RM and Sharma, A and Stenger, E and Ustun, C and Williams, KM and Vrooman, LM and Satwani, P and Phelan, R},
title = {Late effects after allogeneic haematopoietic cell transplantation in children and adolescents with non-malignant disorders: a retrospective cohort study.},
journal = {The Lancet. Child & adolescent health},
volume = {},
number = {},
pages = {},
doi = {10.1016/S2352-4642(24)00167-6},
pmid = {39217999},
issn = {2352-4650},
abstract = {BACKGROUND: Continued advances in haematopoietic cell transplantation (HCT) for children with non-malignant diseases (NMDs) have led to a growing population of survivors in whom late occurring toxic effects remain a challenge. We investigated the incidence of and risk factors for post-transplant toxicities in a contemporary cohort of children and adolescents undergoing HCT for NMDs.

METHODS: In this retrospective cohort study, we extracted data from the Center for International Blood and Marrow Transplantation Research (CIBMTR) database to analyse timing and incidence of effects and risk factors associated with late effects of HCT for treatment of NMDs at age 21 years or younger. Late effects of interest were avascular necrosis, cataracts, congestive heart failure, myocardial infarction, diabetes, gonadal dysfunction, growth hormone deficiency, hypothyroidism, renal failure requiring dialysis, and neurological events (stroke and seizure). Cumulative incidence of each late effect was calculated at 5 years and 7 years after HCT. Risk factors were evaluated in Cox proportional hazards regression analyses. Main exposures were primary NMD, age, sex, ethnicity and race, insurance, donor and graft type, myoablative conditioning, total-body irradiation exposure, graft-versus-host disease (GVHD), and transplant year. Primary outcomes were rates, cumulative incidence probability (95% CI), and risk-factors for organ-specific late effects.

FINDINGS: Between Jan 1, 2000, and Dec 31, 2017, 7785 patients aged 21 years or younger underwent HCT. 1995 patients were ineligible or did not consent to be included. 5790 patients from 171 centres were included in the analysis. 3505 (60·5%) of 5790 patients were male and 2285 (39·5%) were female. 2106 (36·4%) patients were White, 771 (13·3%) were Hispanic, and 773 (12·7%) were Black. 1790 (30·9%) patients were non-USA residents. Median age at HCT was 5·5 years (range 0·0-21·0). 1127 (19%) of 5790 patients had one late effect, and 381 (7%) had at least two. At 7 years post-HCT, the cumulative incidence probability was 1·9 (95% CI 1·5-2·3) for cataracts, 4·9 (4·3-5·6) for diabetes, 2·6 (2·1-3·1) for gonadal dysfunction, 3·2 (2·7-3·8) for hypothyroidism, 5·0 (4·4-5·7) for growth disturbance, 8·1 (7·4-8·9) for renal failure, 1·6 (1·3-2·0) for avascular necrosis, 0·6 (0·4-0·8) for congestive heart failure, 0·2 (0·1-0·3) for myocardial infarction, and 9·4 (8·6-10·2) for neurological effects. Age 10 years or older at HCT, unrelated donor source, total-body irradiation, and GVHD were identified as risk factors for long-term effects.

INTERPRETATION: The findings highlight the need for, and access to, multidisciplinary and lifelong follow-up for children undergoing HCT for NMDs. As more children undergo treatment with cellular therapies for non-malignant conditions, further analyses of post-transplant data could increasingly guide treatment decisions and subsequent long-term surveillance.

FUNDING: National Cancer Institute, National Heart, Lung and Blood Institute, National Institute of Allergy and Infectious Diseases, Health Resources and Services Administration, and Office of Naval Research.},
}

@article {pmid39213169,
year = {2024},
author = {Andrews, KR and Besser, TE and Stalder, T and Top, EM and Baker, KN and Fagnan, MW and New, DD and Schneider, GM and Gal, A and Andrews-Dickert, R and Hunter, SS and Beckmen, KB and Christensen, L and Justice-Allen, A and Konetchy, D and Lehman, CP and Manlove, K and Miyasaki, H and Nordeen, T and Roug, A and Cassirer, EF},
title = {Comparative genomic analysis identifies potential adaptive variation in Mycoplasma ovipneumoniae.},
journal = {Microbial genomics},
volume = {10},
number = {8},
pages = {},
pmid = {39213169},
issn = {2057-5858},
mesh = {Animals ; *Mycoplasma ovipneumoniae/genetics ; *Goats/microbiology ; *Phylogeny ; Sheep/microbiology ; *Genome, Bacterial ; Genomics ; Reindeer/microbiology ; China ; Sheep Diseases/microbiology ; Adaptation, Physiological/genetics ; Australia ; Pneumonia, Mycoplasma/microbiology/veterinary ; },
abstract = {Mycoplasma ovipneumoniae is associated with respiratory disease in wild and domestic Caprinae globally, with wide variation in disease outcomes within and between host species. To gain insight into phylogenetic structure and mechanisms of pathogenicity for this bacterial species, we compared M. ovipneumoniae genomes for 99 samples from 6 countries (Australia, Bosnia and Herzegovina, Brazil, China, France and USA) and 4 host species (domestic sheep, domestic goats, bighorn sheep and caribou). Core genome sequences of M. ovipneumoniae assemblies from domestic sheep and goats fell into two well-supported phylogenetic clades that are divergent enough to be considered different bacterial species, consistent with each of these two clades having an evolutionary origin in separate host species. Genome assemblies from bighorn sheep and caribou also fell within these two clades, indicating multiple spillover events, most commonly from domestic sheep. Pangenome analysis indicated a high percentage (91.4 %) of accessory genes (i.e. genes found only in a subset of assemblies) compared to core genes (i.e. genes found in all assemblies), potentially indicating a propensity for this pathogen to adapt to within-host conditions. In addition, many genes related to carbon metabolism, which is a virulence factor for Mycoplasmas, showed evidence for homologous recombination, a potential signature of adaptation. The presence or absence of annotated genes was very similar between sheep and goat clades, with only two annotated genes significantly clade-associated. However, three M. ovipneumoniae genome assemblies from asymptomatic caribou in Alaska formed a highly divergent subclade within the sheep clade that lacked 23 annotated genes compared to other assemblies, and many of these genes had functions related to carbon metabolism. Overall, our results suggest that adaptation of M. ovipneumoniae has involved evolution of carbon metabolism pathways and virulence mechanisms related to those pathways. The genes involved in these pathways, along with other genes identified as potentially involved in virulence in this study, are potential targets for future investigation into a possible genomic basis for the high variation observed in disease outcomes within and between wild and domestic host species.},
}

Animals
*Mycoplasma ovipneumoniae/genetics
*Goats/microbiology
*Phylogeny
Sheep/microbiology
*Genome, Bacterial
Genomics
Reindeer/microbiology
China
Sheep Diseases/microbiology
Adaptation, Physiological/genetics
Australia
Pneumonia, Mycoplasma/microbiology/veterinary

@article {pmid39209823,
year = {2024},
author = {Baden, LR and El Sahly, HM and Essink, B and Follmann, D and Hachigian, G and Strout, C and Overcash, JS and Doblecki-Lewis, S and Whitaker, JA and Anderson, EJ and Neuzil, K and Corey, L and Priddy, F and Tomassini, JE and Brown, M and Girard, B and Stolman, D and Urdaneta, V and Wang, X and Deng, W and Zhou, H and Dixit, A and Das, R and Miller, JM and , },
title = {Long-term safety and effectiveness of mRNA-1273 vaccine in adults: COVE trial open-label and booster phases.},
journal = {Nature communications},
volume = {15},
number = {1},
pages = {7469},
pmid = {39209823},
issn = {2041-1723},
support = {UM1 AI068614/AI/NIAID NIH HHS/United States ; UM1 AI068618/AI/NIAID NIH HHS/United States ; UM1 AI148684/AI/NIAID NIH HHS/United States ; UM1 AI068635/AI/NIAID NIH HHS/United States ; UM1 AI068619/AI/NIAID NIH HHS/United States ; UM1 AI068636/AI/NIAID NIH HHS/United States ; },
mesh = {Humans ; *2019-nCoV Vaccine mRNA-1273/immunology ; *COVID-19/prevention & control/immunology ; *Immunization, Secondary ; Adult ; Male ; Female ; *SARS-CoV-2/immunology ; Middle Aged ; *COVID-19 Vaccines/immunology/adverse effects/administration & dosage ; Vaccine Efficacy ; Antibodies, Viral/immunology/blood ; Immunogenicity, Vaccine ; Aged ; Young Adult ; Vaccination ; Adolescent ; },
abstract = {Primary vaccination with mRNA-1273 (100-µg) was safe and efficacious at preventing coronavirus disease 2019 (COVID-19) in the previously reported, blinded Part A of the phase 3 Coronavirus Efficacy (COVE; NCT04470427) trial in adults (≥18 years) across 99 U.S. sites. The open-label (Parts B and C) primary objectives were evaluation of long-term safety and effectiveness of primary vaccination plus a 50-µg booster dose; immunogenicity was a secondary objective. Of 29,035 open-label participants, 19,609 received boosters (mRNA-1273 [n = 9647]; placebo-mRNA-1273 [n = 9952]; placebo [n = 10] groups). Booster safety was consistent with that reported for primary vaccination. Incidences of COVID-19 and severe COVID-19 were higher during the Omicron BA.1 than Delta variant waves and boosting versus non-boosting was associated with a significant, 47.0% (95% CI : 39.0-53.9%) reduction of Omicron BA.1 incidence (24.6 [23.4 - 25.8] vs 46.4 [40.6 - 52.7]/1000 person-months). In an exploratory Cox regression model adjusted for time-varying covariates, a longer median interval between primary vaccination and boosting (mRNA-1273 [13 months] vs placebo-mRNA-1273 [8 months]) was associated with significantly lower, COVID-19 risk (24.0% [16.0% - 32.0%]) during Omicron BA.1 predominance. Boosting elicited greater immune responses against SARS-CoV-2 than primary vaccination, irrespective of prior SARS-CoV-2 infection. Primary vaccination and boosting with mRNA-1273 demonstrated acceptable safety, effectiveness and immunogenicity against COVID-19, including emergent variants.},
}

Humans
*2019-nCoV Vaccine mRNA-1273/immunology
*COVID-19/prevention & control/immunology
*Immunization, Secondary
Adult
Male
Female
*SARS-CoV-2/immunology
Middle Aged
*COVID-19 Vaccines/immunology/adverse effects/administration & dosage
Vaccine Efficacy
Antibodies, Viral/immunology/blood
Immunogenicity, Vaccine
Aged
Young Adult
Vaccination
Adolescent

@article {pmid39211945,
year = {2024},
author = {Huang, IJ and Baek, GT and Siu, C and Shadman, M},
title = {Pharmacological management of chronic lymphocytic leukemia: current and emerging therapies.},
journal = {Expert opinion on pharmacotherapy},
volume = {},
number = {},
pages = {1-25},
doi = {10.1080/14656566.2024.2398603},
pmid = {39211945},
issn = {1744-7666},
abstract = {INTRODUCTION: Chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL), characterized by its monoclonal lymphoproliferative nature, is an indolent but incurable malignancy. The treatment landscape of CLL/SLL has drastically transformed in the last decade since the introduction of targeted therapy and immune-effector T-cell therapy. The paradigm shift from chemoimmunotherapy to targeted and cellular therapies was largely driven by improved efficacy and safety. With the success of targeted therapies, novel agents and combinations are rapidly emerging on the horizon.

AREAS COVERED: In this review, we will summarize clinical evidence supporting current and emerging therapies with emphasis on investigational therapies and novel combinations of commercial agents. Clinical trials were identified via clinicaltrials.gov, and a PubMed literature search was last performed in June 2024.

EXPERT OPINION: With the availability of more effective and better-tolerated treatments for CLL/SLL, the role of early intervention should be further investigated due to its potential to alter disease course, delay progression, and improve overall survival rates. With many highly effective agents and combinations expected to become commercially available, attention to safety profiles and careful selection of patients for each treatment will be critical, with consideration of comorbidities, logistical issues, and financial burden of treatment.},
}

@article {pmid39210036,
year = {2024},
author = {Othus, M and Baccon, D and Ali, N and Rodríguez-Arbolí, E and Orvain, C and Milano, F and Sandmaier, BM and Davis, C and Basom, RS and Walter, RB},
title = {Relationship between morphologic remission with or without hematologic recovery and outcome after allogeneic hematopoietic cell transplantation in adult acute myeloid leukemia.},
journal = {Bone marrow transplantation},
volume = {},
number = {},
pages = {},
pmid = {39210036},
issn = {1476-5365},
support = {P01-CA078902//U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)/ ; P01-CA018029//U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)/ ; P30-CA015704//U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)/ ; },
abstract = {Outcomes of adults with AML after allografting vary widely. While numerous covariates have been associated with relapse, non-relapse mortality (NRM), and/or shorter survival, the impact of incomplete blood count recovery before transplantation has remained unclear. To address this uncertainty, we examined all adults with AML or MDS/AML who received an allograft in first or second remission between 2006 and 2023 at a single institution. Of 1264 patients, 891 (70%) met criteria for CR, whereas 291 (23%), 24 (2%), and 58 (5%) were classified as CRh, CRi, and morphologic leukemia-free state (MLFS), respectively. CR, CRh, CRi, and MLFS patients differed significantly regarding demographics, disease biology, pre-transplant measurable residual disease, and types of transplants. After multivariable adjustment, outcomes for CRh and CRi patients were not significantly different from each other or from those of CR patients. In contrast, outcomes of MLFS patients were substantially worse than those of CR and CRh patients, with significantly higher risk of NRM and relapse, and significantly shorter relapse-free and overall survival. Similar results were obtained in several distinct subsets. Together, our analysis provides empiric evidence for the importance of distinguishing MLFS from CR and CRh patients for optimized risk assessment and, possibly, individualized treatment decision making.},
}

@article {pmid39210026,
year = {2024},
author = {Repetto, L and Chen, J and Yang, Z and Zhai, R and Timmers, PRHJ and Feng, X and Li, T and Yao, Y and Maslov, D and Timoshchuk, A and Tu, F and Twait, EL and May-Wilson, S and Muckian, MD and Prins, BP and Png, G and Kooperberg, C and Johansson, Å and Hillary, RF and Wheeler, E and Pan, L and He, Y and Klasson, S and Ahmad, S and Peters, JE and Gilly, A and Karaleftheri, M and Tsafantakis, E and Haessler, J and Gyllensten, U and Harris, SE and Wareham, NJ and Göteson, A and Lagging, C and Ikram, MA and van Duijn, CM and Jern, C and Landén, M and Langenberg, C and Deary, IJ and Marioni, RE and Enroth, S and Reiner, AP and Dedoussis, G and Zeggini, E and Sharapov, S and Aulchenko, YS and Butterworth, AS and Mälarstig, A and Wilson, JF and Navarro, P and Shen, X},
title = {The genetic landscape of neuro-related proteins in human plasma.},
journal = {Nature human behaviour},
volume = {},
number = {},
pages = {},
pmid = {39210026},
issn = {2397-3374},
support = {12171495//National Natural Science Foundation of China (National Science Foundation of China)/ ; 2021A1515010866//Natural Science Foundation of Guangdong Province (Guangdong Natural Science Foundation)/ ; 2022-01309//Vetenskapsrådet (Swedish Research Council)/ ; },
abstract = {Understanding the genetic basis of neuro-related proteins is essential for dissecting the molecular basis of human behavioural traits and the disease aetiology of neuropsychiatric disorders. Here the SCALLOP Consortium conducted a genome-wide association meta-analysis of over 12,000 individuals for 184 neuro-related proteins in human plasma. The analysis identified 125 cis-regulatory protein quantitative trait loci (cis-pQTL) and 164 trans-pQTL. The mapped pQTL capture on average 50% of each protein's heritability. At the cis-pQTL, multiple proteins shared a genetic basis with human behavioural traits such as alcohol and food intake, smoking and educational attainment, as well as neurological conditions and psychiatric disorders such as pain, neuroticism and schizophrenia. Integrating with established drug information, the causal inference analysis validated 52 out of 66 matched combinations of protein targets and diseases or side effects with available drugs while suggesting hundreds of repurposing and new therapeutic targets.},
}

@article {pmid39209385,
year = {2024},
author = {Deschamps, MM and Bat-Erdene, M and Duerr, A and Pape, JW},
title = {GHESKIO's model of patient care during civil unrest in Haiti.},
journal = {The lancet. HIV},
volume = {11},
number = {9},
pages = {e572-e573},
doi = {10.1016/S2352-3018(24)00208-X},
pmid = {39209385},
issn = {2352-3018},
mesh = {Humans ; Haiti/epidemiology ; *HIV Infections/epidemiology/prevention & control ; Patient Care ; Delivery of Health Care ; },
}

Humans
Haiti/epidemiology
*HIV Infections/epidemiology/prevention & control
Patient Care
Delivery of Health Care

@article {pmid39208801,
year = {2024},
author = {Long, D and Chan, M and Han, M and Kamdar, Z and Ma, RK and Tsai, PY and Francisco, AB and Barrow, J and Shackelford, DB and Yarchoan, M and McBride, MJ and Orre, LM and Vacanti, NM and Gujral, TS and Sethupathy, P},
title = {Proteo-metabolomics and patient tumor slice experiments point to amino acid centrality for rewired mitochondria in fibrolamellar carcinoma.},
journal = {Cell reports. Medicine},
volume = {},
number = {},
pages = {101699},
doi = {10.1016/j.xcrm.2024.101699},
pmid = {39208801},
issn = {2666-3791},
abstract = {Fibrolamellar carcinoma (FLC) is a rare, lethal, early-onset liver cancer with a critical need for new therapeutics. The primary driver in FLC is the fusion oncoprotein, DNAJ-PKAc, which remains challenging to target therapeutically. It is critical, therefore, to expand understanding of the FLC molecular landscape to identify druggable pathways/targets. Here, we perform the most comprehensive integrative proteo-metabolomic analysis of FLC. We also conduct nutrient manipulation, respirometry analyses, as well as key loss-of-function assays in FLC tumor tissue slices from patients. We propose a model of cellular energetics in FLC pointing to proline anabolism being mediated by ornithine aminotransferase hyperactivity and ornithine transcarbamylase hypoactivity with serine and glutamine catabolism fueling the process. We highlight FLC's potential dependency on voltage-dependent anion channel (VDAC), a mitochondrial gatekeeper for anions including pyruvate. The metabolic rewiring in FLC that we propose in our model, with an emphasis on mitochondria, can be exploited for therapeutic vulnerabilities.},
}

@article {pmid39208097,
year = {2024},
author = {Martin, S and Scorzoni, S and Cordone, S and Mazzagatti, A and Beznoussenko, GV and Gunn, AL and Di Bona, M and Eliezer, Y and Leor, G and Ben-Yishay, T and Loffreda, A and Cancila, V and Rainone, MC and Ippolito, MR and Martis, V and Bedin, F and Garrè, M and Vaites, LP and Vasapolli, P and Polo, S and Parazzoli, D and Tripodo, C and Mironov, AA and Cuomo, A and Ben-David, U and Bakhoum, SF and Hatch, EM and Ly, P and Santaguida, S},
title = {A p62-dependent rheostat dictates micronuclei catastrophe and chromosome rearrangements.},
journal = {Science (New York, N.Y.)},
volume = {385},
number = {6712},
pages = {eadj7446},
doi = {10.1126/science.adj7446},
pmid = {39208097},
issn = {1095-9203},
mesh = {Humans ; *Sequestosome-1 Protein/metabolism/genetics ; *Chromosomal Instability ; *Chromothripsis ; *Autophagy ; *Micronuclei, Chromosome-Defective ; *Colorectal Neoplasms/genetics/pathology/metabolism ; Cell Line, Tumor ; DNA Damage ; Endosomal Sorting Complexes Required for Transport/metabolism/genetics ; Mitochondria/metabolism/genetics ; Nuclear Envelope/metabolism ; },
abstract = {Chromosomal instability (CIN) generates micronuclei-aberrant extranuclear structures that catalyze the acquisition of complex chromosomal rearrangements present in cancer. Micronuclei are characterized by persistent DNA damage and catastrophic nuclear envelope collapse, which exposes DNA to the cytoplasm. We found that the autophagic receptor p62/SQSTM1 modulates micronuclear stability, influencing chromosome fragmentation and rearrangements. Mechanistically, proximity of micronuclei to mitochondria led to oxidation-driven homo-oligomerization of p62, limiting endosomal sorting complex required for transport (ESCRT)-dependent micronuclear envelope repair by triggering autophagic degradation. We also found that p62 levels correlate with increased chromothripsis across human cancer cell lines and with increased CIN in colorectal tumors. Thus, p62 acts as a regulator of micronuclei and may serve as a prognostic marker for tumors with high CIN.},
}

Humans
*Sequestosome-1 Protein/metabolism/genetics
*Chromosomal Instability
*Chromothripsis
*Autophagy
*Micronuclei, Chromosome-Defective
*Colorectal Neoplasms/genetics/pathology/metabolism
Cell Line, Tumor
DNA Damage
Endosomal Sorting Complexes Required for Transport/metabolism/genetics
Mitochondria/metabolism/genetics
Nuclear Envelope/metabolism

@article {pmid39207900,
year = {2024},
author = {Elum, JE and Szelenyi, ER and Juarez, B and Murry, AD and Loginov, G and Zamorano, CA and Gao, P and Wu, G and Ng-Evans, S and Yee, JX and Xu, X and Golden, SA and Zweifel, LS},
title = {Distinct dynamics and intrinsic properties in ventral tegmental area populations mediate reward association and motivation.},
journal = {Cell reports},
volume = {43},
number = {9},
pages = {114668},
doi = {10.1016/j.celrep.2024.114668},
pmid = {39207900},
issn = {2211-1247},
abstract = {Ventral tegmental area (VTA) dopamine neurons regulate reward-related associative learning and reward-driven motivated behaviors, but how these processes are coordinated by distinct VTA neuronal subpopulations remains unresolved. Here, we compare the contribution of two primarily dopaminergic and largely non-overlapping VTA subpopulations, all VTA dopamine neurons and VTA GABAergic neurons of the mouse midbrain, to these processes. We find that the dopamine subpopulation that projects to the nucleus accumbens (NAc) core preferentially encodes reward-predictive cues and prediction errors. In contrast, the subpopulation that projects to the NAc shell preferentially encodes goal-directed actions and relative reward anticipation. VTA GABA neuron activity strongly contrasts VTA dopamine population activity and preferentially encodes reward outcome and retrieval. Electrophysiology, targeted optogenetics, and whole-brain input mapping reveal multiple convergent sources that contribute to the heterogeneity among VTA dopamine subpopulations that likely underlies their distinct encoding of reward-related associations and motivation that defines their functions in these contexts.},
}

@article {pmid39207259,
year = {2024},
author = {Serrano-Villar, S and Gala, A and Bacchetti, P and Hoh, R and di Germanio, C and Cohn, LB and Henrich, TJ and Hunt, PW and Laird, GM and Pillai, SK and Deeks, SG and Peluso, MJ},
title = {Galectin-9 Levels as a Potential Predictor of Intact HIV Reservoir Decay.},
journal = {The Journal of infectious diseases},
volume = {},
number = {},
pages = {},
doi = {10.1093/infdis/jiae426},
pmid = {39207259},
issn = {1537-6613},
abstract = {BACKGROUND: During antiretroviral therapy (ART), the HIV reservoir exhibits variability as cells with intact genomes decay faster than those with defective genomes, especially in the first years of therapy. The host factors influencing this decay are yet to be characterized.

METHODS: Observational study in 74 PWH on ART, of whom 70 (94.6%) were male. We used the intact proviral DNA assay to measure intact proviruses and Luminex immunoassay to measure 32 inflammatory cytokines in plasma. Linear spline models, with a knot at seven years, evaluated the impact of baseline cytokine levels and their trajectories on intact HIV kinetics over these years.

RESULTS: Baseline Gal-9 was the most predictive marker for intact HIV kinetics, with lower Gal-9 predicting faster decay over the subsequent seven years. For each 10-fold decrease in Gal-9 at baseline, there was a mean 45% (95%CI 14%-84%) greater decay of intact HIV genomes per year. Conversely, higher baseline ITAC, IL-17, and MIP-1α predicted faster intact HIV decreases. Longitudinal changes in MIP-3α and IL-6 levels strongly associated with intact HIV kinetics, with a 10-fold increase in MIP-3α and a 10-fold decrease in IL-6 associated with a a 9.5% and 10% faster decay of intact HIV genomes per year, respectively.

CONCLUSION: The pronounced association between baseline Gal-9 levels and subsequent intact HIV decay suggests that strategies reducing Gal-9 levels could accelerate reservoir decay. Additionally, the correlations of MIP-3α and IL-6 with HIV kinetics indicate a broader cytokine-mediated regulatory network, hinting at multi-targeted interventions that could modulate HIV reservoir dynamics.},
}

@article {pmid39206927,
year = {2024},
author = {Neary, J and Chebet, D and Benki-Nugent, S and Moraa, H and Richardson, BA and Njuguna, I and Langat, A and Ngugi, E and Lehman, DA and Slyker, J and Wamalwa, D and John-Stewart, G},
title = {Association between HIV and cytomegalovirus and neurocognitive outcomes among children with HIV.},
journal = {AIDS (London, England)},
volume = {},
number = {},
pages = {},
doi = {10.1097/QAD.0000000000004000},
pmid = {39206927},
issn = {1473-5571},
abstract = {OBJECTIVES: Children with HIV may experience adverse neurocognitive outcomes despite antiretroviral therapy (ART). Cytomegalovirus (CMV) is common in children with HIV. Among children on ART, we examined the influences of early HIV viral load (VL) and CMV DNA on neurocognition.

DESIGN: We determined the association between pre-ART VL, cumulative VL, and CMV viremia and neurocognition using data from a cohort study.

METHODS: Children who initiated ART before 12 months of age were enrolled from 2007-2010 in Nairobi, Kenya. Blood was collected at enrollment and every 6 months thereafter. Four neurocognitive assessments with 12 domains were conducted when children were a median age of 7 years. Primary outcomes included cognitive ability, executive function, attention, and motor. Generalized linear models were used to determine associations between HIV VL (pre-ART and cumulative; N = 38) and peak CMV DNA (by 24 months of age; N = 20) and neurocognitive outcomes.

RESULTS: In adjusted models, higher peak CMV viremia by 24 months of age was associated with lower cognitive ability and motor z-scores. Higher pre-ART HIV VL was associated with lower executive function z-scores. Among secondary outcomes, higher pre-ART VL was associated with lower mean nonverbal and metacognition z-scores.

CONCLUSION: Higher pre-ART VL and CMV DNA in infancy were associated with lower executive function, nonverbal and metacognition scores and cognitive ability scores in childhood, respectively. These findings suggest long-term benefits of early HIV viral suppression and CMV control on neurocognition.},
}

@article {pmid39197073,
year = {2024},
author = {Chakraborty, R and Zanwar, S and Hegenbart, U and Bhutani, D and Gertz, MA and Dispenzieri, A and Kumar, SK and D'Souza, A and Patwari, A and Cowan, AJ and Chen, G and Milani, P and Palladini, G and Sanchorawala, V and Bodanapu, G and Schönland, S and Lentzsch, S and Muchtar, E},
title = {Prognostic impact of cytogenetic abnormalities by FISH in AL amyloidosis with daratumumab-based frontline therapy.},
journal = {Blood},
volume = {},
number = {},
pages = {},
doi = {10.1182/blood.2024025899},
pmid = {39197073},
issn = {1528-0020},
abstract = {We performed an international retrospective cohort study to investigate the prognostic impact of cytogenetic abnormalities by FISH in 283 patients with AL amyloidosis treated with frontline daratumumab-bortezomib-cyclophosphamide-dexamethasone (Dara-VCD) or Dara-VD. The cytogenetic subgroups of interest were t(11;14), gain/amp(1q) [hereafter, +1q], hyperdiploidy, deletion(13q), del(17p), and myeloma high-risk (HR) translocations (t[4;14], t[14;16], or t[14;20]). The endpoints of interest were rate of hematologic complete response (heme CR), very good partial response or better (≥VGPR), and hematologic event-free survival (Heme EFS). The incidence of abnormalities was following: t(11;14)-53.4%; deletion (13q)-28.9%; +1q-22.3%; hyperdiploidy-19.4%; HR translocations-6.6%; and deletion(17p)-4.5%. The heme-CR rate by cytogenetic subgroups were: t(11;14) vs no t(11;14)-45.2% vs 41.8% (p=0.597); del(13q) vs no del(13q)-46.8% vs 42.8% (p=0.594); +1q vs no +1q-30.2% vs 47.9% (p=0.022); hyperdiploidy vs no hyperdiploidy-39.5% vs 44.9% (p=0.541); HR translocations vs none: 45.5% vs 43.1% (p=0.877); and del(17p) vs no del(17p)-50.0% vs 42.9% respectively (p=0.658). Similarly, +1q was the only subgroup with a significantly lower ≥VGPR rate (64.2% vs 79.0%; p=0.033). At a median follow-up of 19.8 months, the median heme-EFS was 49.6 months (95% CI, 24.7-not reached [NR]), and the 2-year OS was 80.98% (95% CI, 75.6-85.4). The presence of+1q was significantly associated with worse heme-EFS on multivariate analysis (HR 2.06, 95% CI, 1.14-3.71; p=0.017). Notably, there was no adverse prognostic impact of t(11;14) on heme EFS or OS. In conclusion, +1q is associated with worse outcome in the daratumumab-era. Clinical trials testing novel immunotherapies frontline should be enriched in +1q to further improve outcomes in this subgroup.},
}

@article {pmid39196656,
year = {2024},
author = {Drowne, T and Armgardt, E and Svoboda, A},
title = {Real-world experience of abemaciclib for adjuvant and metastatic breast cancer.},
journal = {Journal of oncology pharmacy practice : official publication of the International Society of Oncology Pharmacy Practitioners},
volume = {},
number = {},
pages = {10781552241279189},
doi = {10.1177/10781552241279189},
pmid = {39196656},
issn = {1477-092X},
abstract = {OBJECTIVE: Hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) breast cancer is the most common subtype. Abemaciclib, an inhibitor of cyclin-dependent kinases 4 and 6, was approved to reduce risk of recurrence in high-risk, HR+, HER2-, early breast cancer based on the monarchE trial. The most common adverse events reported in monarchE were diarrhea, neutropenia, and fatigue. Real-world tolerability data and incidence of adverse events with abemaciclib in the adjuvant setting versus the metastatic setting is lacking.

DATA SOURCES: This is a retrospective analysis of HR+, HER2- breast cancer patients on abemaciclib from March 2018 to September 2021 at Robert H. Lurie Comprehensive Cancer Center in Chicago, Illinois. Incidence, grade of adverse events, dose reductions, and discontinuations were evaluated in patients taking abemaciclib in the adjuvant setting and the metastatic setting.

DATA SUMMARY: Of the 30 patients included in this analysis, 100% experienced an adverse event of any grade. During treatment, 12.5% treated in the adjuvant setting and 35.7% in the metastatic setting experienced grade ≥3 adverse events. Adverse events leading to discontinuation of abemaciclib occurred in 18.8% of patients in the adjuvant setting and 57.1% in the metastatic setting.

CONCLUSIONS: This data suggests abemaciclib is better tolerated in high-risk, HR+, HER2-, node-positive, early breast cancer treated in the adjuvant setting compared to the metastatic setting. Management of adverse events is crucial to help patients stay on therapy to improve clinical outcomes. Real-world tolerability of abemaciclib in both the adjuvant and metastatic settings is of importance.},
}

@article {pmid39195559,
year = {2024},
author = {Navarro, SL and Williamson, BD and Huang, Y and Nagana Gowda, GA and Raftery, D and Tinker, LF and Zheng, C and Beresford, SAA and Purcell, H and Djukovic, D and Gu, H and Strickler, HD and Tabung, FK and Prentice, RL and Neuhouser, ML and Lampe, JW},
title = {Metabolite Predictors of Breast and Colorectal Cancer Risk in the Women's Health Initiative.},
journal = {Metabolites},
volume = {14},
number = {8},
pages = {},
pmid = {39195559},
issn = {2218-1989},
support = {75N92021D00002/HL/NHLBI NIH HHS/United States ; 75N92021D00005/WH/WHI NIH HHS/United States ; R01 CA277133/CA/NCI NIH HHS/United States ; S10 OD021562/CD/ODCDC CDC HHS/United States ; 75N92021D00001/HL/NHLBI NIH HHS/United States ; R01 CA119171/CA/NCI NIH HHS/United States ; 75N92021D00003/WH/WHI NIH HHS/United States ; P30 DK035816/DK/NIDDK NIH HHS/United States ; 75N92021D00001 75N92021D00002 75N92021D00003 75N92021D00004 75N92021D00005//NHLBI, NIH, USDHHS/ ; 75N92021D00004/WH/WHI NIH HHS/United States ; S10 OD021562/OD/NIH HHS/United States ; P30 CA015704/CA/NCI NIH HHS/United States ; },
abstract = {Metabolomics has been used extensively to capture the exposome. We investigated whether prospectively measured metabolites provided predictive power beyond well-established risk factors among 758 women with adjudicated cancers [n = 577 breast (BC) and n = 181 colorectal (CRC)] and n = 758 controls with available specimens (collected mean 7.2 years prior to diagnosis) in the Women's Health Initiative Bone Mineral Density subcohort. Fasting samples were analyzed by LC-MS/MS and lipidomics in serum, plus GC-MS and NMR in 24 h urine. For feature selection, we applied LASSO regression and Super Learner algorithms. Prediction models were subsequently derived using logistic regression and Super Learner procedures, with performance assessed using cross-validation (CV). For BC, metabolites did not increase predictive performance over established risk factors (CV-AUCs~0.57). For CRC, prediction increased with the addition of metabolites (median CV-AUC across platforms increased from ~0.54 to ~0.60). Metabolites related to energy metabolism: adenosine, 2-hydroxyglutarate, N-acetyl-glycine, taurine, threonine, LPC (FA20:3), acetate, and glycerate; protein metabolism: histidine, leucic acid, isoleucine, N-acetyl-glutamate, allantoin, N-acetyl-neuraminate, hydroxyproline, and uracil; and dietary/microbial metabolites: myo-inositol, trimethylamine-N-oxide, and 7-methylguanine, consistently contributed to CRC prediction. Energy metabolism may play a key role in the development of CRC and may be evident prior to disease development.},
}

@article {pmid39192316,
year = {2024},
author = {Fahrmann, JF and Ghasemi, SM and Han, CY and Wu, R and Dennison, JB and Vykoukal, J and Celestino, J and Lu, K and Lu, Z and Drescher, C and Do, KA and Hanash, S and Bast, RC and Irajizad, E},
title = {A metabolite-based liquid biopsy for detection of ovarian cancer.},
journal = {Biomarker research},
volume = {12},
number = {1},
pages = {91},
pmid = {39192316},
issn = {2050-7771},
abstract = {Serial CA125 and second line transvaginal ultrasound (TVS) screening in the UKCTOCS indicated a shift towards detection of earlier stage ovarian cancer (OvCa), but did not yield a significant mortality reduction. There remains a need to establish additional biomarkers that can complement CA125 for even earlier and at a larger proportion of new cases. Using a cohort of plasma samples from 219 OvCa cases (59 stage I/II and 160 stage III/IV) and 409 female controls and a novel Sensitivity Maximization At A Given Specificity (SMAGS) method, we developed a blood-based metabolite-based test consisting of 7 metabolites together with CA125 for detection of OvCa. At a 98.5% specificity cutpoint, the metabolite test achieved sensitivity of 86.2% for detection of early-stage OvCa and was able to capture 64% of the cases with low CA125 levels (< 35 units/mL). In an independent test consisting of 65 early-stage OvCa cases and 141 female controls, the metabolite panel achieved sensitivity of 73.8% at a 91.4% specificity and captured 13 (44.8%) out of 29 early-stage cases with CA125 levels < 35 units/mL. The metabolite test has utility for ovarian cancer screening, capable of improving upon CA125 for detection of early-stage disease.},
}

@article {pmid39191946,
year = {2024},
author = {Javed, Z and Shin, DH and Pan, W and White, SR and Elhaw, AT and Kim, YS and Kamlapurkar, S and Cheng, YY and Benson, JC and Abdelnaby, AE and Phaëton, R and Wang, HG and Yang, S and Sullivan, MLG and St Croix, CM and Watkins, SC and Mullett, SJ and Gelhaus, SL and Lee, N and Coffman, LG and Aird, KM and Trebak, M and Mythreye, K and Walter, V and Hempel, N},
title = {Drp1 splice variants regulate ovarian cancer mitochondrial dynamics and tumor progression.},
journal = {EMBO reports},
volume = {},
number = {},
pages = {},
pmid = {39191946},
issn = {1469-3178},
support = {W81XWH-16-1-0117//U.S. Department of Defense (DOD)/ ; W81XWH-22-10252//U.S. Department of Defense (DOD)/ ; R01CA242021//HHS | NIH | National Cancer Institute (NCI)/ ; R01CA230628//HHS | NIH | National Cancer Institute (NCI)/ ; P50CA272218//HHS | NIH | National Cancer Institute (NCI)/ ; P30CA047904//HHS | NIH | National Cancer Institute (NCI)/ ; 2T32HL110849-11A1//HHS | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; R35HL150778//HHS | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; S10OD023402//HHS | NIH | NIH Office of the Director (OD)/ ; S10RR025488//HHS | NIH | National Center for Research Resources (NCRR)/ ; S10RR016236//HHS | NIH | National Center for Research Resources (NCRR)/ ; S10RR019003//HHS | NIH | National Center for Research Resources (NCRR)/ ; },
abstract = {Aberrant mitochondrial fission/fusion dynamics are frequently associated with pathologies, including cancer. We show that alternative splice variants of the fission protein Drp1 (DNM1L) contribute to the complexity of mitochondrial fission/fusion regulation in tumor cells. High tumor expression of the Drp1 alternative splice variant lacking exon 16 relative to other transcripts is associated with poor outcome in ovarian cancer patients. Lack of exon 16 results in Drp1 localization to microtubules and decreased association with mitochondrial fission sites, culminating in fused mitochondrial networks, enhanced respiration, changes in metabolism, and enhanced pro-tumorigenic phenotypes in vitro and in vivo. These effects are inhibited by siRNAs designed to specifically target the endogenously expressed transcript lacking exon 16. Moreover, lack of exon 16 abrogates mitochondrial fission in response to pro-apoptotic stimuli and leads to decreased sensitivity to chemotherapeutics. These data emphasize the pathophysiological importance of Drp1 alternative splicing, highlight the divergent functions and consequences of changing the relative expression of Drp1 splice variants in tumor cells, and strongly warrant consideration of alternative splicing in future studies focused on Drp1.},
}

@article {pmid39191731,
year = {2024},
author = {Banerjee, R and Biru, Y and Cole, CE and Faiman, B and Midha, S and Ailawadhi, S},
title = {Disparities in relapsed or refractory multiple myeloma: recommendations from an interprofessional consensus panel.},
journal = {Blood cancer journal},
volume = {14},
number = {1},
pages = {149},
pmid = {39191731},
issn = {2044-5385},
mesh = {*Multiple Myeloma/therapy/drug therapy/epidemiology/diagnosis ; Humans ; *Healthcare Disparities ; Consensus ; United States/epidemiology ; },
abstract = {Many studies have documented racial, socioeconomic, geographic, and other disparities for United States (US) patients with multiple myeloma pertaining to diagnosis and frontline management. In contrast, very little is known about disparities in the management of relapsed/refractory multiple myeloma (RRMM) despite a plethora of novel treatment options. In this review, we discuss the manifestations of disparities in RRMM and strategies to mitigate their impact. Immunomodulatory drugs can create disparities on many axes, for example inappropriately low dosing due to Duffy-null status as well as time toxicity and financial toxicity from logistical hurdles for socioeconomically vulnerable patients. Access to myeloma expertise at high-volume centers is a critical consideration given the disconnect between how drugs like carfilzomib and dexamethasone are prescribed in trials versus optimized in real-world practice to lower toxicities. Disparities in chimeric antigen receptor T-cell therapy and bispecific antibody therapy span across racial, ethnic, and socioeconomic lines in large part due to their limited availability outside of high-volume centers. Another insidious source of disparities is supportive care in RRMM, ranging from inadequate pain control in Black patients to limited primary care provider access in rural settings. We discuss the rationales and evidence base for several solutions aimed at mitigating these disparities: for example, (1) bidirectional co-management with community-based oncologists, (2) screening for risk factors based on social determinants of health, (3) strategies to build patient trust with regard to clinical trials, and (4) longitudinal access to a primary care provider. As the treatment landscape for RRMM continues to expand, these types of efforts by the field will help ensure that this landscape is equally accessible and traversable for all US patients.},
}

*Multiple Myeloma/therapy/drug therapy/epidemiology/diagnosis
Humans
*Healthcare Disparities
Consensus
United States/epidemiology

@article {pmid39191530,
year = {2024},
author = {Borazanci, EH and Bahary, N and Chung, V and Huyck, TK and Kio, EA and Chiorean, EG and Skeel, RT and Alese, OB and Cardin, DB and Fountzilas, C and Hanna, WT and Leal, AD and Lee, V and Noonan, AM and Philip, PA and Wainberg, ZA and Pashova, H and Mann, G and Oberstein, PE},
title = {Relacorilant plus nab-paclitaxel for the treatment of metastatic pancreatic ductal adenocarcinoma: results from the open-label RELIANT study.},
journal = {The oncologist},
volume = {},
number = {},
pages = {},
doi = {10.1093/oncolo/oyae210},
pmid = {39191530},
issn = {1549-490X},
support = {//Corcept Therapeutics/ ; },
abstract = {BACKGROUND: Modulation of glucocorticoid receptor (GR) activity in tumor cells enhances chemotherapy efficacy. We evaluated the selective GR modulator relacorilant plus nab-paclitaxel in patients with metastatic pancreatic ductal adenocarcinoma (mPDAC) who had received at least 2 prior therapy lines.

PATIENTS AND METHODS: In this open-label, single-arm, phase III study, patients received once-daily oral relacorilant (100 mg, titrated to 150 mg in 25 mg increments/cycle) and nab-paclitaxel (80 mg/m2) on days 1, 8, and 15 of 28-day cycles. The primary efficacy endpoint was objective response rate (ORR) by blinded independent central review. Progression-free survival (PFS), overall survival (OS), target gene modulation, and safety were also assessed.

RESULTS: Of 43 patients enrolled, 31 were evaluable for ORR (12 did not reach first postbaseline radiographic assessment). An interim analysis to assess whether ORR was ≥10% showed no confirmed responses and the study was discontinued. Two (6.5%) patients attained unconfirmed partial responses and 15 (48.4%) had stable disease. Fourteen of 31 (45.2%) patients had reductions in target lesion size, despite prior nab-paclitaxel exposure in 12 of the 14. Median PFS and OS were 2.4 months (95% CI, 1.4-4.2) and 3.9 months (95% CI, 2.8-4.9), respectively. The most common adverse events were fatigue and nausea. RNA analysis confirmed that relacorilant plus nab-paclitaxel suppressed 8 cortisol target genes of interest.

CONCLUSION: Relacorilant plus nab-paclitaxel showed modest antitumor activity in heavily pretreated patients with mPDAC, with no new safety signals. Studies of this combination in other indications with a high unmet medical need are ongoing.},
}

@article {pmid39191488,
year = {2024},
author = {Driessen, A and Unger, S and Nguyen, AP and Ries, RE and Meshinchi, S and Kreutmair, S and Alberti, C and Sumazin, P and Aplenc, R and Redell, MS and Becher, B and Rodríguez Martínez, M},
title = {Identification of single-cell blasts in pediatric acute myeloid leukemia using an autoencoder.},
journal = {Life science alliance},
volume = {7},
number = {11},
pages = {},
pmid = {39191488},
issn = {2575-1077},
support = {U10 CA180886/CA/NCI NIH HHS/United States ; U10 CA180899/CA/NCI NIH HHS/United States ; U24 CA196173/CA/NCI NIH HHS/United States ; },
mesh = {Humans ; *Leukemia, Myeloid, Acute/pathology/immunology/genetics ; Child ; *Single-Cell Analysis/methods ; *Immunophenotyping ; Female ; Male ; Child, Preschool ; Adolescent ; Myeloid-Lymphoid Leukemia Protein/genetics/metabolism ; Flow Cytometry/methods ; Infant ; Histone-Lysine N-Methyltransferase/genetics/metabolism ; Computational Biology/methods ; Prognosis ; },
abstract = {Pediatric acute myeloid leukemia (AML) is an aggressive blood cancer with a poor prognosis and high relapse rate. Current challenges in the identification of immunotherapy targets arise from patient-specific blast immunophenotypes and their change during disease progression. To overcome this, we present a new computational research tool to rapidly identify malignant cells. We generated single-cell flow cytometry profiles of 21 pediatric AML patients with matched samples at diagnosis, remission, and relapse. We coupled a classifier to an autoencoder for anomaly detection and classified malignant blasts with 90% accuracy. Moreover, our method assigns a developmental stage to blasts at the single-cell level, improving current classification approaches based on differentiation of the dominant phenotype. We observed major immunophenotype and developmental stage alterations between diagnosis and relapse. Patients with KMT2A rearrangement had more profound changes in their blast immunophenotypes at relapse compared to patients with other molecular features. Our method provides new insights into the immunophenotypic composition of AML blasts in an unbiased fashion and can help to define immunotherapy targets that might improve personalized AML treatment.},
}

Humans
*Leukemia, Myeloid, Acute/pathology/immunology/genetics
Child
*Single-Cell Analysis/methods
*Immunophenotyping
Female
Male
Child, Preschool
Adolescent
Myeloid-Lymphoid Leukemia Protein/genetics/metabolism
Flow Cytometry/methods
Infant
Histone-Lysine N-Methyltransferase/genetics/metabolism
Computational Biology/methods
Prognosis

@article {pmid39190070,
year = {2024},
author = {Purice, MD and Severs, LJ and Singhvi, A},
title = {Glia in Invertebrate Models: Insights from Caenorhabditis elegans.},
journal = {Advances in neurobiology},
volume = {39},
number = {},
pages = {19-49},
pmid = {39190070},
issn = {2190-5215},
mesh = {Animals ; *Caenorhabditis elegans ; *Neuroglia/metabolism ; Models, Animal ; },
abstract = {Glial cells modulate brain development, function, and health across all bilaterian animals, and studies in the past two decades have made rapid strides to uncover the underlying molecular mechanisms of glial functions. The nervous system of the invertebrate genetic model Caenorhabditis elegans (C. elegans) has small cell numbers with invariant lineages, mapped connectome, easy genetic manipulation, and a short lifespan, and the animal is also optically transparent. These characteristics are revealing C. elegans to be a powerful experimental platform for studying glial biology. This chapter discusses studies in C. elegans that add to our understanding of how glia modulate adult neural functions, and thereby animal behaviors, as well as emerging evidence of their roles as autonomous sensory cells. The rapid molecular and cellular advancements in understanding C. elegans glia in recent years underscore the utility of this model in studies of glial biology. We conclude with a perspective on future research avenues for C. elegans glia that may readily contribute molecular mechanistic insights into glial functions in the nervous system.},
}

Animals
*Caenorhabditis elegans
*Neuroglia/metabolism
Models, Animal

@article {pmid39189966,
year = {2024},
author = {Zhang, Y and Lindström, S and Kraft, P and Liu, Y},
title = {Genetic Risk, Health-Associated Lifestyle, and Risk of Early-onset Total Cancer and Breast Cancer.},
journal = {Journal of the National Cancer Institute},
volume = {},
number = {},
pages = {},
doi = {10.1093/jnci/djae208},
pmid = {39189966},
issn = {1460-2105},
abstract = {BACKGROUND: Early-onset cancer (diagnosed under age 50) generally manifests as an aggressive disease phenotype. The association between healthy lifestyle and early-onset cancer and whether it varies by common genetic variants remains unclear.

METHODS: We analyzed a prospective cohort of 66,308 participants who were under age 50 and free of cancer at baseline in the UK Biobank. Using Cox regression, we estimated Hazard ratios (HRs) and 95% confidence intervals (CIs) for early-onset total and breast cancer based on sex-specific composite total cancer polygenic risk scores (PRSs), a breast cancer-specific PRS, and sex-specific health-associated lifestyle scores (HLSs).

RESULTS: In multivariable-adjusted analyses with 2-year latency, higher genetic risk (highest vs lowest tertile of PRS) was associated with significantly increased risks of early-onset total cancer in females (HR, 95% CI: 1.83, 1.49-2.26) and males (2.03, 1.51-2.73) as well as early-onset breast cancer in females (3.06, 2.20-4.26). An unfavorable lifestyle (highest vs lowest category of HLS) was associated with higher risk of total cancer and breast cancer in females across genetic risk categories; the association with total cancer and breast cancer was stronger in the highest genetic risk category than the lowest: HRs (95% CIs) were 1.55 (1.12, 2.14) and 1.69 (1.11, 2.57) in the highest genetic risk category and 1.03 (0.64, 1.67) and 0.81 (0.36, 1.85) in the lowest.

CONCLUSIONS: Genetic and lifestyle factors were independently associated with early-onset total and breast cancer risk. Individuals with a high genetic risk may benefit more from adopting a healthy lifestyle in preventing early-onset cancer.},
}

@article {pmid39189932,
year = {2024},
author = {Epperla, N and Zayac, AS and Landsburg, DJ and Bock, AM and Nowakowski, GS and Ayers, EC and Girton, MR and Hu, M and Beckman, AK and Li, S and Medeiros, LJ and Chang, JE and Kurt, H and Sandoval-Sus, J and Ansari-Lari, MA and Kothari, SK and Kress, A and Xu, ML and Torka, P and Sundaram, S and Smith, SD and Naresh, KN and Karimi, YH and Bond, DA and Evens, AM and Naik, SG and Kamdar, M and Haverkos, BM and Karmali, R and Farooq, U and Vose, JM and Rubinstein, PG and Chaudhry, A and Olszewski, AJ},
title = {High-Grade B-Cell Lymphoma, Not Otherwise Specified: CNS Involvement and Outcomes in a Multi-Institutional Series.},
journal = {Blood advances},
volume = {},
number = {},
pages = {},
doi = {10.1182/bloodadvances.2024013791},
pmid = {39189932},
issn = {2473-9537},
abstract = {Little is known about the central nervous system (CNS) risk in high-grade B-cell lymphoma, not otherwise specified (HGBL, NOS). Hence, we sought to describe the rates of baseline CNS involvement, risk of CNS recurrence after primary therapy, and management strategies in HGBL, NOS. In this multicenter retrospective study, we included 160 adults with newly diagnosed HGBL, NOS treated between 2016 and 2021 at 20 US institutions. Eleven patients (7%) had baseline CNS involvement at diagnosis (leptomeningeal=6, parenchymal=4, and both=1). Baseline CNS involvement was significantly associated only with MYC rearrangement (OR=3.5) and testicular (in men) or female pelvic (in women) involvement (OR=8.1). There was no significant difference in survival outcomes between HGBL, NOS patients with (median PFS=4 years) or without (median PFS=2.4 years) baseline CNS involvement (p=0.45). The cumulative incidence of CNS recurrence at 3 years was 11%. Patients with baseline CNS involvement were at the highest risk (48.5% versus 8% for those without baseline CNS involvement) and were excluded from the risk factors analysis for CNS recurrence. The risk for CNS recurrence was significantly associated with blood or bone marrow involvement, CD5 expression, non-GCB subtype, and DEL phenotype, however, high CNS-IPI was not. The prognosis of relapsed HGBL, NOS was poor, regardless of whether recurrence was systemic or limited to the CNS, and with currently available salvage strategies, including autologous transplantation and CAR T-cell modalities, almost all patients with CNS recurrence ultimately succumbed to their disease. These patients represent an unmet need and should be prioritized for experimental approaches.},
}

@article {pmid39189646,
year = {2024},
author = {Lin, L and Huang, Y and McIntyre, J and Chang, CH and Colmenares, S and Lee, YCG},
title = {Prevalent fast evolution of genes involved in heterochromatin functions.},
journal = {Molecular biology and evolution},
volume = {},
number = {},
pages = {},
doi = {10.1093/molbev/msae181},
pmid = {39189646},
issn = {1537-1719},
abstract = {Heterochromatin is a gene-poor and repeat-rich genomic compartment universally found in eukaryotes. Despite its low transcriptional activity, heterochromatin plays important roles in maintaining genome stability, organizing chromosomes, and suppressing transposable elements (TEs). Given the importance of these functions, it is expected that the genes involved in heterochromatin regulation would be highly conserved. Yet, a handful of these genes were found to evolve rapidly. To investigate whether these previous findings are anecdotal or general to genes modulating heterochromatin, we compile an exhaustive list of 106 candidate genes involved in heterochromatin functions and investigate their evolution over short and long evolutionary time scales in Drosophila. Our analyses find that these genes exhibit significantly more frequent evolutionary changes, both in the forms of amino acid substitutions and gene copy number change, when compared to genes involved in Polycomb-based repressive chromatin. While positive selection drives amino acid changes within both structured domains with diverse functions and intrinsically disordered regions (IDRs), purifying selection may have maintained the proportions of IDRs of these proteins. Together with the observed negative associations between evolutionary rates of these genes and genomic TE abundance, we propose an evolutionary model where the fast evolution of genes involved in heterochromatin functions is an inevitable outcome of the unique functional roles of heterochromatin, while the rapid evolution of TEs may be an effect rather than cause. Our study provides an important global view of the evolution of genes involved in this critical cellular domain and provides insights into the factors driving the distinctive evolution of heterochromatin.},
}

@article {pmid39187601,
year = {2024},
author = {Marcoux, CM and Alousi, AM and Im, J and Hill, LC and Smallbone, P and Popat, U and Hosing, C and Kebriaei, P and Olson, A and Mehta, R and Chen, G and Qazilbash, M and Shpall, E and Champlin, RC and Saliba, RM},
title = {Gastrointestinal involvement refines prognosis in minnesota standard risk acute graft-vs.-host disease.},
journal = {Bone marrow transplantation},
volume = {},
number = {},
pages = {},
pmid = {39187601},
issn = {1476-5365},
abstract = {Minnesota acute graft versus host disease (AGVHD) risk score is a validated tool to stratify newly-diagnosed patients into standard-risk (SR) and high-risk (HR) groups with ~85% having SR AGVHD. We aimed to identify factors for further risk-stratification within Minnesota SR patients. A single-center, retrospective analysis of consecutive patients between 1/2010 and 12/2014 was performed. Patients who developed AGVHD within 100 days and treated with systemic corticosteroids were included (N = 416), 356 (86%) of which were Minnesota SR and 60 (14%) had HR AGVHD. Isolated upper gastrointestinal (GI) AGVHD patients had significantly better day 28 and 56 CR/PR rates (90% vs. 72%, p = 0.004) and (83% vs 66%, p = 0.01), respectively, and lower 1-year non-relapse mortality (NRM; 10% vs. 22%; HR 0.4, p = 0.03). Lower GI AGVHD had less favorable outcomes with 1-year NRM of 40% (HR 2.1, p = 0.001), although CR/PR rates were not statistically different. In multivariate analysis, lower GI involvement (HR 2.6, p < 0.001), age ≥ 50 (HR 2.9, p < 0.001) and HCT-CI > 3 (HR 2.1, p = 0.002) predicted for 1-year NRM. Heterogeneity within Minnesota SR patients requires consideration in clinical trials, as distinct outcomes are observed in those with isolated upper GI and lower GI AGVHD, highlighting the importance of stratification in clinical trial design.},
}