tbuckley/cabot-search huggingface dataset:
An Evaluation of Sex- and Gender-Based Analyses in Oncology Clinical Trials
Authors: Mathew Hall, Vaishali A Krishnanandan, Matthew C Cheung, Natalie G Coburn, Barbara Haas, Kelvin K W Chan, Michael J Raphael
Journal: JNCI Journal of the National Cancer Institute (2022)

The objective of this study was to evaluate whether sex- and gender-based analyses and proper sex and gender terminology were used in oncology trials leading to regulatory drug approval.The Food and Drug Administration (FDA) Hematology/Oncology Approvals and Safety Notifications page was used to identify all anticancer therapies that received FDA approval between 2012 and 2019. The trials used to support FDA drug approval were collected along with all available supplemental tables and study protocols. Documents were reviewed to determine if there was a plan to analyze results according to sex and gender and to determine if consistent sex and gender terminology were used.We identified 128 randomized, controlled trials corresponding to a cancer medicine, which received FDA approval. No study specified how sex and gender were collected or analyzed. No study reported any information on the gender of participants. Sex and gender terminology were used inconsistently at least once in 76% (97 of 128) of studies. Among the 102 trials for nonsex-specific cancer sites, 89% (91 of 102) presented disaggregated survival outcome data by sex. No study presented disaggregated toxicity data by sex or gender.The majority of pivotal clinical trials in oncology fail to account for the important distinction between sex and gender and conflate sex and gender terminology. More rigor in designing clinical trials to include sex- and gender-based analyses and more care in using sex and gender terms in the cancer literature are needed. These efforts are essential to improve the reproducibility, generalizability, and inclusiveness of cancer research.
Metabolically driven maturation of human-induced-pluripotent-stem-cell-derived cardiac microtissues on microfluidic chips
Authors: Nathaniel Huebsch, Berenice Charrez, Gabriel Neiman, Brian Siemons, Steven C. Boggess, Samuel Wall, Verena Charwat, Karoline H. Jæger, David Cleres, Åshild Telle, Felipe T. Lee-Montiel, Nicholas C. Jeffreys, Nikhil Deveshwar, Andrew G. Edwards, Jonathan Serrano, Matija Snuderl, Andreas Stahl, Aslak Tveito, Evan W. Miller, Kevin E. Healy
Journal: Nature Biomedical Engineering (2022)
Ulcerated Plaques on the Scalp and Dorsal Hands of an Older Man
Authors: Amrita Goyal, Daniel O’Leary, Misha Rosenbach
Journal: JAMA (2022)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Mild Intermittent Hypoxia: A New Treatment Approach for Patients with Obstructive Sleep Apnea and Hypertension
Authors: Riken Chen, Dongxing Zhao, Qinglan Wu, Xiaojuan Chen, Jiangpeng Lin, Donghao Wang, Mingdi Chen, Junyan Lin, Zhenzhen Zheng
Journal: American Journal of Respiratory and Critical Care Medicine (2022)
Recommendations for the management of COVID-19 in patients with haematological malignancies or haematopoietic cell transplantation, from the 2021 European Conference on Infections in Leukaemia (ECIL 9)
Authors: Simone Cesaro, Per Ljungman, Malgorzata Mikulska, Hans H. Hirsch, Marie von Lilienfeld-Toal, Catherine Cordonnier, Sylvain Meylan, Varun Mehra, Jan Styczynski, Francesco Marchesi, Caroline Besson, Fausto Baldanti, Raul Cordoba Masculano, Gernot Beutel, Herman Einsele, Elie Azoulay, Johan Maertens, Rafael de la Camara, Marie von Lilienfeld-Toal, Rafael de la Camara, Livio Pagano
Journal: Leukemia (2022)
NAFLD‐related hepatocellular carcinoma: The growing challenge
Authors: Pir Ahmad Shah, Rashmee Patil, Stephen A. Harrison
Journal: Hepatology (2022)

Hepatocellular carcinoma (HCC) is a common cause of cancer‐related mortality and morbidity worldwide. With the obesity pandemic, NAFLD‐related HCC is contributing to the burden of disease exponentially. Genetic predisposition and clinical risk factors for NAFLD‐related HCC have been identified. Cirrhosis is a well‐known and major risk factor for NAFLD‐related HCC. However, the occurrence of NAFLD‐related HCC in patients without cirrhosis is increasingly recognized and poses a significant challenge regarding cancer surveillance. It is of paramount importance to develop optimal risk stratification scores and models to identify subsets of the population at high risk so they can be enrolled in surveillance programs. In this review, we will discuss the risks and prediction models for NAFLD‐related HCC.
The ORATOR Trials Have Spoken—Where Do We Go From Here?
Authors: Sewit Teckie, Neil D. Gross
Journal: JAMA Oncology (2022)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Oncology HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Oncology journal
Different Genes are Recruited During Convergent Evolution of Pregnancy and the Placenta
Authors: Charles S.P. Foster, James U. Van Dyke, Michael B. Thompson, Nicholas M.A. Smith, Colin A. Simpfendorfer, Christopher R. Murphy, Camilla M. Whittington
Journal: Molecular Biology and Evolution (2022)

Abstract The repeated evolution of the same traits in distantly related groups (convergent evolution) raises a key question in evolutionary biology: do the same genes underpin convergent phenotypes? Here, we explore one such trait, viviparity (live birth), which, qualitative studies suggest, may indeed have evolved via genetic convergence. There are &amp;gt;150 independent origins of live birth in vertebrates, providing a uniquely powerful system to test the mechanisms underpinning convergence in morphology, physiology, and/or gene recruitment during pregnancy. We compared transcriptomic data from eight vertebrates (lizards, mammals, sharks) that gestate embryos within the uterus. Since many previous studies detected qualitative similarities in gene use during independent origins of pregnancy, we expected to find significant overlap in gene use in viviparous taxa. However, we found no more overlap in uterine gene expression associated with viviparity than we would expect by chance alone. Each viviparous lineage exhibits the same core set of uterine physiological functions. Yet, contrary to prevailing assumptions about this trait, we find that none of the same genes are differentially expressed in all viviparous lineages, or even in all viviparous amniote lineages. Therefore, across distantly related vertebrates, different genes have been recruited to support the morphological and physiological changes required for successful pregnancy. We conclude that redundancies in gene function have enabled the repeated evolution of viviparity through recruitment of different genes from genomic “toolboxes”, which are uniquely constrained by the ancestries of each lineage.
Subclonal evolution of CLL driver mutations is associated with relapse in ibrutinib- and acalabrutinib-treated patients
Authors: Gage S. Black, Xiaomeng Huang, Yi Qiao, Szabolcs Tarapcsak, Kerry A. Rogers, Shrilekha Misra, John C. Byrd, Gabor T. Marth, Deborah M. Stephens, Jennifer A. Woyach
Journal: Blood (2022)
Climate Warming Since the Holocene Accelerates West–East Communication for the Eurasian Temperate Water Strider Species<i>Aquarius paludum</i>
Authors: Zhen Ye, Juanjuan Yuan, Jakob Damgaard, Gavril Marius Berchi, Fabio Cianferoni, Matthew R. Pintar, Horea Olosutean, Xiuxiu Zhu, Kun Jiang, Xin Yang, Siying Fu, Wenjun Bu
Journal: Molecular Biology and Evolution (2022)

Holocene climate warming has dramatically altered biological diversity and distributions. Recent human-induced emissions of greenhouse gases will exacerbate global warming and thus induce threats to cold-adapted taxa. However, the impacts of this major climate change on transcontinental temperate species are still poorly understood. Here, we generated extensive genomic datasets for a water strider, Aquarius paludum, which was sampled across its entire distribution in Eurasia and used these datasets in combination with ecological niche modeling (ENM) to elucidate the influence of the Holocene and future climate warming on its population structure and demographic history. We found that A. paludum consisted of two phylogeographic lineages that diverged in the middle Pleistocene, which resulted in a "west-east component" genetic pattern that was probably triggered by Central Asia-Mongoxin aridification and Pleistocene glaciations. The diverged western and eastern lineages had a second contact in the Holocene, which shaped a temporary hybrid zone located at the boundary of the arid-semiarid regions of China. Future predictions detected a potentially novel northern corridor to connect the western and eastern populations, indicating west-east gene flow would possibly continue to intensify under future warming climate conditions. Further integrating phylogeographic and ENM analyses of multiple Eurasian temperate taxa based on published studies reinforced our findings on the "west-east component" genetic pattern and the predicted future northern corridor for A. paludum. Our study provided a detailed paradigm from a phylogeographic perspective of how transcontinental temperate species differ from cold-adapted taxa in their response to climate warming.
<i>Notes from the Field:</i> Response to Measles Among Persons Evacuated from Afghanistan — Joint Base McGuire-Dix-Lakehurst, New Jersey, August–October 2021
Authors: Nikki Pritchard, Mary Claire Worrell, Andrea Shahum, Angel Nwankwo, Dallas Smith, John J. Koch, Timothy Ballard
Journal: MMWR Morbidity and Mortality Weekly Report (2022)

On August 29, 2021, the U.S. government initiated Operation Allies Welcome (OAW) to resettle eligible persons from Afghanistan.Evacuees were housed at military bases in the United States while completing immigration resettlement processing.On September 4, 2021, the Fort McCoy, Wisconsin, OAW site reported the first confirmed case of measles in an Afghan evacuee; during the subsequent 10 days, five additional cases were identified across multiple sites (1).On September 6, OAW response leadership learned that 16 evacuees at Joint Base McGuire-Dix-Lakehurst (JBMDL) had been exposed to a patient with confirmed measles during a September 3 United States-bound flight.Because of low routine measles vaccination coverage rates in Afghanistan (2), risk for measles transmission was high among evacuees at JBMDL, a population that would expand to >10,000 persons living in large tents and multifamily rooms, if any exposed evacuees developed measles.During September 7-9, the JBMDL OAW public health team, with support from local and state health departments and guidance from CDC, provided measles, mumps, and rubella (MMR) vaccine or immunoglobulin to exposed persons.Because of delayed reporting of the exposures and challenges locating evacuees, whose lodgings assignments were not always well documented or might have changed, postexposure prophylaxis was not administered within the recommended time frame.*Exposed persons were asked to quarantine and complied; however, because of space constraints, they were not moved into quarantine until 1 week after the exposure.None of the evacuees exposed to the patient on September 3 experienced measles signs or symptoms † during quarantine.This activity was reviewed by CDC and was conducted consistent with applicable federal law and CDC policy.§ * For postexposure prophylaxis, MMR vaccine should be administered within 72 hours or immunoglobulin within 6 days of initial measles exposure.All 16 exposed persons were placed in a 21-day quarantine based on date of last exposure (i.e., September 3).https://www.cdc.gov/measles/hcp/index.html#prophylaxis; https://www.cdc.gov/vaccines/pubs/surv-manual/chpt07-measles.pdf† Quarantined persons were monitored for signs and symptoms of measles per the case definition of the Council of State and Territorial Epidemiologists.https://ndc.services.cdc.gov/case-definitions/measles-2013/
Addition of interleukin-2 overcomes resistance to neoadjuvant CTLA4 and PD1 blockade in ex vivo patient tumors
Authors: Paulien Kaptein, Celia Jacoberger-Foissac, Petros Dimitriadis, Paula Voabil, Marjolein de Bruijn, Simone Brokamp, Irene Reijers, Judith Versluis, Gahyathiri Nallan, Hannah Triscott, Elizabeth McDonald, Joshua Tay, Georgina V. Long, Christian U. Blank, Daniela S. Thommen, Michele W.L. Teng
Journal: Science Translational Medicine (2022)

Neoadjuvant immunotherapy with anti-cytotoxic T lymphocyte–associated protein 4 (CTLA4) + anti–programmed cell death protein 1 (PD1) monoclonal antibodies has demonstrated remarkable pathological responses and relapse-free survival in ~80% of patients with clinically detectable stage III melanoma. However, about 20% of the treated patients do not respond. In pretreatment biopsies of patients with melanoma, we found that resistance to neoadjuvant CTLA4 + PD1 blockade was associated with a low CD4/interleukin-2 (IL-2) gene signature. Ex vivo, addition of IL-2 to CTLA4 + PD1 blockade induced T cell activation and deep immunological responses in anti-CTLA4 + anti-PD1–resistant human tumor specimens. In the 4T1.2 breast cancer mouse model of neoadjuvant immunotherapy, triple combination of anti-CTLA4 + anti-PD1 + IL-2 cured almost twice as many mice as compared with dual checkpoint inhibitor therapy. This improved efficacy was due to the expansion of tumor-specific CD8 + T cells and improved proinflammatory cytokine polyfunctionality of both CD4 + and CD8 + T effector cells and regulatory T cells. Depletion studies suggested that CD4 + T cells were critical for priming of CD8 + T cell immunity against 4T1.2 and helped in the expansion of tumor-specific CD8 + T cells early after neoadjuvant triple immunotherapy. Our results suggest that the addition of IL-2 can overcome resistance to neoadjuvant anti-CTLA4 + anti-PD1, providing the rationale for testing this combination as a neoadjuvant therapy in patients with early-stage cancer.
Synonymous Variants: Necessary Nuance in Our Understanding of Cancer Drivers and Treatment Outcomes
Authors: Nayiri M Kaissarian, Douglas Meyer, Chava Kimchi-Sarfaty
Journal: JNCI Journal of the National Cancer Institute (2022)

Once called "silent mutations" and assumed to have no effect on protein structure and function, synonymous variants are now recognized to be drivers for some cancers. There have been significant advances in our understanding of the numerous mechanisms by which synonymous single nucleotide variants (sSNVs) can affect protein structure and function by affecting pre-mRNA splicing, mRNA expression, stability, folding, micro-RNA binding, translation kinetics, and co-translational folding. This review highlights the need for considering sSNVs in cancer biology to gain a better understanding of the genetic determinants of human cancers and to improve their diagnosis and treatment. We surveyed the literature for reports of sSNVs in cancer and found numerous studies on the consequences of sSNVs on gene function with supporting in vitro evidence. We also found reports of sSNVs that have statistically significant associations with specific cancer types but for which in vitro studies are lacking to support the reported associations. Additionally, we found reports of germline and somatic sSNVs that were observed in numerous clinical studies and for which in silico analysis predicts possible effects on gene function. We provide a review of these investigations and discuss necessary future studies to elucidate the mechanisms by which sSNVs disrupt protein function and play a role in tumorigeneses, cancer progression, and treatment efficacy. As splicing dysregulation is one of the most well-recognized mechanisms by which sSNVs impact protein function, we also include our own in silico analysis for predicting which sSNVs may disrupt pre-mRNA splicing.
Hypercoagulability, endotheliopathy, and inflammation approximating 1 year after recovery: Assessing the long‐term outcomes in <scp>COVID</scp>‐19 patients
Authors: Bingwen Eugene Fan, Shiun Woei Wong, Christina Lai Lin Sum, Gek Hsiang Lim, Bernard PuiLam Leung, Chuen Wen Tan, Kollengode Ramanathan, Rinkoo Dalan, Christine Cheung, Xin Rong Lim, Mucheli Shravan Sadasiv, David Chien Lye, Barnaby Edward Young, Eng Soo Yap, Yew Woon Chia
Journal: American Journal of Hematology (2022)

Abstract Sustained hypercoagulability and endotheliopathy are present in convalescent COVID‐19 patients for up to 4 months from recovery. The hemostatic, endothelial, and inflammatory profiles of 39 recovered COVID‐19 patients were evaluated up to 16 months after recovery from COVID‐19. These values were compared with a control group of healthy volunteers ( n = 124). 39 patients (71.8% males, median age 43 years) were reviewed at a mean of 12.7 ± 3.6 months following recovery. One patient without cardiovascular risk factors had post COVID‐19 acute ischaemic limb. Elevated D‐dimer and Factor VIII levels above normal ranges were noted in 17.9% (7/39) and 48.7% (19/39) of patients respectively, with a higher median D‐dimer 0.34 FEU μg/mL (IQR 0.28, 0.46) ( p &lt; .001) and Factor VIII 150% (IQR 171, 203) ( p = .004), versus controls. Thrombin generation (Thromboscreen) showed a higher median endogenous thrombin potential (ETP) of 1352 nM*min (IQR 1152, 1490) ( p = .002) and a higher median peak height of 221.4 nM (IQR 170.2, 280.4) ( p = 0.01) and delayed lag time 2.4 min (1.42–2.97) ( p = 0.0002) versus controls. Raised vWF:Ag and ICAM‐1 levels were observed in 17.9% (7/39) and 7.7% (3/39) of patients respectively, with a higher median VWF:Ag 117% (IQR 86, 154) ( p = 0.02) and ICAM‐1 54.1 ng/mL (IQR 43.8, 64.1) ( p = .004) than controls. IL‐6 was noted to be raised in 35.9% (14/39) of patients, with a higher median IL‐6 of 1.5 pg/mL (IQR 0.6, 3.0) ( p = 0.004) versus controls. Subgroup analysis stratifying patients by COVID‐19 severity and COVID‐19 vaccination preceding SARS‐CoV‐2 infection did not show statistically significant differences. Hypercoagulability, endothelial dysfunction, and inflammation are still detectable in some patients approximately 1 year after recovery from COVID‐19.
Global spatial dynamics and vaccine-induced fitness changes of <i>Bordetella pertussis</i>
Authors: Noémie Lefrancq, Valérie Bouchez, Nadia Fernandes, Alex-Mikael Barkoff, Thijs Bosch, Tine Dalby, Thomas Åkerlund, Jessica Darenberg, Katerina Fabianova, Didrik F. Vestrheim, Norman K. Fry, Juan José González-López, Karolina Gullsby, Adele Habington, Qiushui He, David Litt, Helena Martini, Denis Piérard, Paola Stefanelli, Marc Stegger, Jana Zavadilova, Nathalie Armatys, Annie Landier, Sophie Guillot, Samuel L. Hong, Philippe Lemey, Julian Parkhill, Julie Toubiana, Simon Cauchemez, Henrik Salje, Sylvain Brisse
Journal: Science Translational Medicine (2022)

As with other pathogens, competitive interactions between Bordetella pertussis strains drive infection risk. Vaccines are thought to perturb strain diversity through shifts in immune pressures; however, this has rarely been measured because of inadequate data and analytical tools. We used 3344 sequences from 23 countries to show that, on average, there are 28.1 transmission chains circulating within a subnational region, with the number of chains strongly associated with host population size. It took 5 to 10 years for B. pertussis to be homogeneously distributed throughout Europe, with the same time frame required for the United States. Increased fitness of pertactin-deficient strains after implementation of acellular vaccines, but reduced fitness otherwise, can explain long-term genotype dynamics. These findings highlight the role of vaccine policy in shifting local diversity of a pathogen that is responsible for 160,000 deaths annually.
Nonlesional lupus skin contributes to inflammatory education of myeloid cells and primes for cutaneous inflammation
Authors: Allison C. Billi, Feiyang Ma, Olesya Plazyo, Mehrnaz Gharaee-Kermani, Rachael Wasikowski, Grace A. Hile, Xianying Xing, Christine M. Yee, Syed M. Rizvi, Mitra P. Maz, Celine C. Berthier, Fei Wen, Lam C. Tsoi, Matteo Pellegrini, Robert L. Modlin, Johann E. Gudjonsson, J. Michelle Kahlenberg
Journal: Science Translational Medicine (2022)

Cutaneous lupus erythematosus (CLE) is a disfiguring and poorly understood condition frequently associated with systemic lupus. Previous studies suggest that nonlesional keratinocytes play a role in disease predisposition, but this has not been investigated in a comprehensive manner or in the context of other cell populations. To investigate CLE immunopathogenesis, normal-appearing skin, lesional skin, and circulating immune cells from lupus patients were analyzed via integrated single-cell RNA sequencing and spatial RNA sequencing. We demonstrate that normal-appearing skin of patients with lupus represents a type I interferon–rich, prelesional environment that skews gene transcription in all major skin cell types and markedly distorts predicted cell-cell communication networks. We also show that lupus-enriched CD16 + dendritic cells undergo robust interferon education in the skin, thereby gaining proinflammatory phenotypes. Together, our data provide a comprehensive characterization of lesional and nonlesional skin in lupus and suggest a role for skin education of CD16 + dendritic cells in CLE pathogenesis.