tbuckley/cabot-search huggingface dataset:
Universal Genetic Testing for Newly Diagnosed Invasive Breast Cancer
Authors: Zoulikha Rezoug, Stephanie P. Totten, David Szlachtycz, Adrienne Atayan, Kristen Mohler, Sophie Albert, Leila Feng, Brianna Lemieux Anglin, Zhen Shen, Daniel Jimenez, Nancy Hamel, Nicholas Meti, Khashayar Esfahani, Jean-François Boileau, Ipshita Prakash, Mark Basik, Sarkis Meterissian, Francine Tremblay, David Fleiszer, Dawn Anderson, George Chong, Stephanie M. Wong, William D. Foulkes
Journal: JAMA Network Open (2024)

Importance Between 5% and 10% of breast cancer cases are associated with an inherited germline pathogenic or likely pathogenic variant (GPV) in a breast cancer susceptibility gene (BCSG), which could alter local and systemic therapy recommendations. Traditional genetic testing criteria misses a proportion of these cases. Objective To evaluate the prevalence and clinicopathological associations of GPVs in 2 groups of BCSGs among an ethnically diverse cohort of women with newly diagnosed breast cancer. Design, Setting, and Participants This cross-sectional study, conducted at 3 Montreal hospitals between September 2019 and April 2022, offered universal genetic counseling and testing to all women with a first diagnosis of invasive breast cancer. Women were offered an obligatory primary panel of BRCA1 , BRCA2 , and PALB2 ( B1B2P2 ) and an optional secondary panel of 14 additional BCSGs. Eligible participants were women 18 years of age or older who received a diagnosis of a first primary invasive breast cancer not more than 6 months before the time of referral to the study. Data were analyzed from November 2023 to June 2024. Results Of 1017 referred patients, 805 were eligible and offered genetic counseling and testing, and 729 of those 805 (90.6%) consented to be tested. The median age at breast cancer diagnosis was 53 years (range, 23-91 years), and 65.4% were White and of European ancestry. Fifty-four GPVs were identified in 53 patients (7.3%), including 39 patients (5.3%) with B1B2P2 and 15 patients (2.1%) with 6 of the 14 secondary panel BCSGs ( ATM , BARD1 , BRIP1 , CHEK2 , RAD51D , and STK11 ). On multivariable analysis, clinical factors independently associated with B1B2P2 -positive status included being younger than 40 years of age at diagnosis (odds ratio [OR], 6.83; 95% CI, 2.22-20.90), triple-negative breast cancer (OR, 3.19; 95% CI, 1.20-8.43), high grade disease (OR, 1.68; 95% CI, 1.05-2.70), and family history of ovarian cancer (OR, 9.75; 95% CI, 2.65-35.85). Of 39 B1B2P2 -positive patients, 13 (33.3%) were eligible for poly(adenosine diphosphate–ribose) polymerase (PARP) inhibitors. Conclusions and Relevance In this cross-sectional universal genetic testing study of women with newly diagnosed invasive breast cancer, the prevalence of GPVs was 7.3%, with 5.3% of patients testing positive for B1B2P2 . Among B1B2P2 -women women, one-third were eligible for PARP inhibitors.
Spatial Variability in Relationships between Early Childhood Lead Exposure and Standardized Test Scores in Fourth Grade North Carolina Public School Students (2013–2016)
Authors: Mercedes A. Bravo, Daniel R. Kowal, Dominique Zephyr, Joseph Feldman, Katherine Ensor, Marie Lynn Miranda
Journal: Environmental Health Perspectives (2024)

Exposure to lead during childhood is detrimental to children's health. The extent to which the association between lead exposure and elementary school academic outcomes varies across geography is not known.
Multi-organ transcriptome atlas of a mouse model of relative energy deficiency in sport
Authors: Laura van Rosmalen, Jiaoyue Zhu, Geraldine Maier, Erica G. Gacasan, Terry Lin, Elena Zhemchuzhnikova, Vince Rothenberg, Swithin Razu, Shaunak Deota, Ramesh K. Ramasamy, Robert L. Sah, Andrew D. McCulloch, Roelof A. Hut, Satchidananda Panda
Journal: Cell Metabolism (2024)

Highlights•We mimic behavior and physiology of REDs in mice using the "exercise-for-food" paradigm•REDs affects extracellular matrix organization in multiple tissues•In females, reproductive organs and muscles are largely affected by energy deficiency•In males, kidneys are largely affected by energy deficiencySummaryInsufficient energy intake to meet energy expenditure demands of physical activity can result in systemic neuroendocrine and metabolic abnormalities in activity-dependent anorexia and relative energy deficiency in sport (REDs). REDs affects >40% of athletes, yet the lack of underlying molecular changes has been a hurdle to have a better understanding of REDs and its treatment. To assess the molecular changes in response to energy deficiency, we implemented the "exercise-for-food" paradigm, in which food reward size is determined by wheel-running activity. By using this paradigm, we replicated several aspects of REDs in female and male mice with high physical activity and gradually reduced food intake, which results in weight loss, compromised bone health, organ-specific mass changes, and altered rest-activity patterns. By integrating transcriptomics of 19 different organs, we provide a comprehensive dataset that will guide future understanding of REDs and may provide important implications for metabolic health and (athletic) performance.Graphical abstract
Errors in the Number of Eligible Bars/Taverns in Study of Closing Hours and Violent Crime
Authors: Erika M. Rosen
Journal: JAMA Internal Medicine (2024)

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 Internal Medicine 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 2024 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 Internal Medicine journal
The association between obesity and malignant progression of Barrett’s Esophagus: a systematic review and dose-response meta-analysis
Authors: Mie Thu Ko, Tom Thomas, Emily Holden, Ian L.P. Beales, Leo Alexandre
Journal: Clinical Gastroenterology and Hepatology (2024)

Background and aimObesity is a risk factor for both Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC). However, it is unclear whether obesity drives the malignant progression of BE. We aimed to assess whether obesity is associated with high-grade dysplasia (HGD) or cancer in patients with BE.MethodsWe searched MEDLINE and EMBASE from inception through April 2024 for studies reporting the effect of body mass index (BMI) on the progression of non-dysplastic BE or low-grade dysplasia (LGD) to HGD or EAC. A two-stage dose response meta-analysis was performed to estimate the dose-response relationship between BMI with malignant progression. Study quality was appraised using a modified Newcastle-Ottawa scale. The review was registered (PROSPERO ID CRD42017051046).ResultsTwenty studies reported data on 38565 patients (74.4% male) in total, of whom 1684 patients were diagnosed with HGD/cancer. Nineteen studies were considered moderate to high quality. Eight cohort studies reported data on 6647 male patients with baseline NDBE/LGD, of whom 555 progressed to HGD/EAC (pooled annual rate of progression 0.02%; 95% CI 0.01%-0.03%) and 1992 female patients with baseline NDBE/LGD with 110 progressors (pooled annual rate of progression 0.01%; 95% CI 0.01%-0.02%). There was no significant difference in pooled annual rate of progression between males and females (p=0.15). Each 5kg/m2 increase in BMI was associated with a 6% increase in the risk of malignant progression (adjusted OR 1.06; 95% CI 1.02-1.10; p<0.001; I2=0%).ConclusionOur meta-analysis provides some evidence that obesity as measured by BMI is associated with malignant progression of BE with a dose-response relationship. This finding requires confirmation in future high-quality cohort studies. Future risk prediction models could incorporate measures of obesity to potentially improve risk stratification in patients with BE.
The influence of MOGAD on diagnosis of multiple sclerosis using MRI
Authors: Ruth Geraldes, Georgina Arrambide, Brenda Banwell, Àlex Rovira, Rosa Cortese, Hans Lassmann, Silvia Messina, Mara Assunta Rocca, Patrick Waters, Declan Chard, Claudio Gasperini, Yael Hacohen, Romina Mariano, Friedemann Paul, Gabriele C. DeLuca, Christian Enzinger, Ludwig Kappos, M. Isabel Leite, Jaume Sastre-Garriga, Tarek Yousry, Olga Ciccarelli, Massimo Filippi, Frederik Barkhof, Jacqueline Palace
Journal: Nature Reviews Neurology (2024)
Long-Term Exposure to Polystyrene Microspheres and High-Fat Diet–Induced Obesity in Mice: Evaluating a Role for Microbiota Dysbiosis
Authors: Zhian Zhai, Ying Yang, Sheng Chen, Zhenlong Wu
Journal: Environmental Health Perspectives (2024)

Microplastics (MPs) have become a global environmental problem, emerging as contaminants with potentially alarming consequences. However, long-term exposure to polystyrene microspheres (PS-MS) and its effects on diet-induced obesity are not yet fully understood.
GLP-1 Receptor Agonist Use and Risk of Suicide Death
Authors: Peter Ueda, Jonas Söderling, Viktor Wintzell, Henrik Svanström, Laura Pazzagli, Björn Eliasson, Mads Melbye, Anders Hviid, Björn Pasternak
Journal: JAMA Internal Medicine (2024)

Importance Concerns have been raised regarding a link between use of glucagon-like peptide-1 (GLP-1) receptor agonists and increased risk of suicidality and self-harm. Objective To assess the association between use of GLP-1 receptor agonists and the risk of suicide death in routine clinical practice. Design, Setting, and Participants This active-comparator new-user cohort study used nationwide register data from Sweden and Denmark from 2013 to 2021. Adults 18 to 84 years old who initiated treatment with GLP-1 receptor agonists or the comparator sodium-glucose cotransporter-2 (SGLT2) inhibitors were included. Data were analyzed from March to June 2024. Exposure Initiation of treatment with a GLP-1 receptor agonist or SGLT2 inhibitor. Main Outcomes and Measures The primary outcome was suicide death recorded in the cause of death registers. Secondary outcomes were the composite of suicide death and nonfatal self-harm and the composite of incident depression and anxiety-related disorders. Using propensity score weighting, hazard ratios (HRs) with 95% CIs were calculated separately in the 2 countries and pooled in a meta-analysis. Results In total, 124 517 adults initiated a GLP-1 receptor agonist and 174 036 initiated an SGLT2 inhibitor; among GLP-1 receptor agonist users, the mean (SD) age was 60 (13) years, and 45% were women. During a mean (SD) follow-up of 2.5 (1.7) years, 77 suicide deaths occurred among users of GLP-1 receptor agonists and 71 suicide deaths occurred among users of SGLT2 inhibitors: weighted incidences were 0.23 vs 0.18 events per 1000 person-years (HR, 1.25; 95% CI, 0.83-1.88), with an absolute difference of 0.05 (95% CI, −0.03 to 0.16) events per 1000 person-years. The HR was 0.83 (95% CI, 0.70-0.97) for suicide death and nonfatal self-harm, and the HR was 1.01 (95% CI, 0.97-1.06) for incident depression and anxiety-related disorders. Conclusions and Relevance This cohort study, including mostly patients with type 2 diabetes, does not show an association between use of GLP-1 receptor agonists and an increased risk of suicide death, self-harm, or incident depression and anxiety-related disorders. Suicide death among GLP-1 receptor agonist users was rare, and the upper limit of the confidence interval was compatible with an absolute risk increase of no more than 0.16 events per 1000 person-years.
Low-Dose Iron and Early Development in Breastfed Infants
Authors: Pin-Yen Chen, Chung-Ming Chen
Journal: JAMA Pediatrics (2024)

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 Pediatrics 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 2024 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 Pediatrics journal
Genome-wide CRISPR/Cas9 library screening identified OGDH as a regulator of disease progress and resistance to decitabine in myelodysplastic neoplasm by reprogramming glutamine metabolism
Authors: Xiaoyan Xu, Jiaqian Qi, Hong Wang, Ziyan Zhang, Tingting Pan, Xueqian Li, Jingyi Yang, Haohao Han, Mengting Guo, Meng Zhou, Chengsen Cai, Yaqiong Tang, Qixiu Hou, Suning Chen, Depei Wu, Yue Han
Journal: Leukemia (2024)
Emergency Department Process Times and Door-In–Door-Out Times in Interhospital Transfers After Acute Ischemic Stroke
Authors: Regina Royan, Brian Stamm, Mihai Giurcanu, Steven R. Messe, Edward C. Jauch, Shyam Prabhakaran
Journal: JAMA Network Open (2024)

Importance Stroke treatment is exquisitely time sensitive. The door-in–door-out (DIDO) time, defined as the total time spent in the emergency department (ED) at a transferring hospital, is an important quality metric for the care of acute stroke. However, little is known about the contributions of specific process steps to delays and disparities in DIDO time. Objective To quantify process steps and their association with DIDO times at transferring hospitals among patients with acute ischemic stroke (AIS). Design, Setting, and Participants This retrospective cohort study analyzed patients in the American Heart Association Get With the Guidelines–Stroke registry with AIS presenting between January 1, 2019, to December 31, 2021, and transferred from the presenting hospital ED to another acute care hospital for evaluation of thrombolytics, endovascular therapy, or postthrombolytic care. Data were analyzed from July 8 to October 13, 2023. Exposures Intervals of ED care of ischemic stroke: door-to-imaging and imaging-to-door times. Main Outcomes and Measures The primary outcome was DIDO time. Multivariate generalized estimating equations regression models were performed to compare contributions of interval process times to explain variation in DIDO time, controlling for patient- and hospital-level characteristics. Results Among 28 887 patients (50.5% male; mean [SD] age, 68.3 [14.8] years; 5.5% Hispanic, 14.7% non-Hispanic Black, and 73.2% non-Hispanic White), mean (SD) DIDO time was 171.4 (149.5) minutes, mean (SD) door-to-imaging time was 18.3 (34.1) minutes, and mean (SD) imaging-to-door time was 153.1 (141.5) minutes. In the model adjusting for door-to-imaging time, the following were associated with longer DIDO time: age 80 years or older (compared with 18-59 years; 5.97 [95% CI, 1.02-10.92] minutes), female sex (5.21 [95% CI, 1.55-8.87] minutes), and non-Hispanic Black race (compared with non-Hispanic White 10.09 [95% CI, 4.21-15.96] minutes). In the model including imaging-to-door time as a covariate, disparities in DIDO by age and female sex became nonsignificant, and the disparity by Black race was attenuated (2.32 [95% CI, 1.09-3.56] minutes). Conclusions and Relevance In this national cohort study of interhospital transfer of patients with AIS, delays in DIDO time by Black race, older age (≥80 years), and female sex were largely explained by the imaging-to-door period, suggesting that future systems interventions should target this interval to reduce these disparities. While existing guidelines and care resources heavily focus on reducing door-to-imaging times, further attention is warranted to reduce imaging-to-door times in the management of patients with AIS who require interhospital transfer.
The WHO genomics program of work for equitable implementation of human genomics for global health
Authors: Elena Ambrosino, Ahmad N. Abou Tayoun, Marc Abramowicz, Bin Alwi Zilfalil, Tiffany Boughtwood, Yosr Hamdi, Tim Hubbard, Kazuto Kato, Iscia Lopes-Cendes, Partha Pratim Majumder, Deborah Mascalzoni, Rokhaya Ndiaye, Michèle Ramsay, Gabriela M. Repetto, Vorasuk Shotelersuk, Sherry Taylor, John C. Reeder, Anna Laura Ross
Journal: Nature Medicine (2024)
A framework for sharing of clinical and genetic data for precision medicine applications
Authors: Ahmed Elhussein, Ulugbek Baymuradov, Noémie Elhadad, Karthik Natarajan, Gamze Gürsoy
Journal: Nature Medicine (2024)

Precision medicine has the potential to provide more accurate diagnosis, appropriate treatment and timely prevention strategies by considering patients' biological makeup. However, this cannot be realized without integrating clinical and omics data in a data-sharing framework that achieves large sample sizes. Systems that integrate clinical and genetic data from multiple sources are scarce due to their distinct data types, interoperability, security and data ownership issues. Here we present a secure framework that allows immutable storage, querying and analysis of clinical and genetic data using blockchain technology. Our platform allows clinical and genetic data to be harmonized by combining them under a unified framework. It supports combined genotype-phenotype queries and analysis, gives institutions control of their data and provides immutable user access logs, improving transparency into how and when health information is used. We demonstrate the value of our framework for precision medicine by creating genotype-phenotype cohorts and examining relationships within them. We show that combining data across institutions using our secure platform increases statistical power for rare disease analysis. By offering an integrated, secure and decentralized framework, we aim to enhance reproducibility and encourage broader participation from communities and patients in data sharing.
Novel Supramolecular Hydrogel for Infected Diabetic Foot Ulcer Treatment
Authors: Wenbiao Zhang, Weiwei Wu, Tao Wang, Zhiwei Wu, Yang Li, Tao Ding, Zhennan Fang, Dasheng Tian, Xiaoyan He, Fei Huang
Journal: Advanced Healthcare Materials (2024)

Abstract Multifunctional responsive hydrogels hold significant promise for diabetic foot ulcer (DFU) treatment, though their complex design and manufacturing present challenges. This study introduces a novel supramolecular guanosine‐phenylboronic‐chlorogenic acid (GBC) hydrogel developed using a dynamic covalent strategy. The hydrogel forms through guanosine quadruplex assembly in the presence of potassium ions and chlorogenic acid (CA) linkage via dynamic borate bonds. GBC hydrogels exhibit pH and glucose responsiveness, releasing more chlorogenic acid under acidic and high glucose conditions due to borate bond dissociation and G‐quadruplex (G4) hydrogel disintegration. Experimental results indicate that GBC hydrogels exhibit good self‐healing, shear‐thinning, injectability, and swelling properties. Both in vitro and in vivo studies demonstrate the GBC hydrogel's good biocompatibility, ability to eliminate bacteria and reactive oxygen species (ROS), facilitate macrophage polarization from the M1 phenotype to the M2 phenotype (decreasing CD86 expression and increasing CD206 expression), exhibit anti‐inflammatory effects (reducing TNF‐α expression and increasing IL‐10 expression), and promote angiogenesis (increasing VEGF, CD31, and α‐SMA expression). Thus, GBC hydrogels accelerate DFU healing and enhance tissue remodeling and collagen deposition. This work provides a new approach to developing responsive hydrogels to expedite DFU healing.
Mucosal adenovirus vaccine boosting elicits IgA and durably prevents XBB.1.16 infection in nonhuman primates
Authors: Matthew Gagne, Barbara J. Flynn, Shayne F. Andrew, Josue Marquez, Dillon R. Flebbe, Anna Mychalowych, Evan Lamb, Meredith E. Davis-Gardner, Matthew R. Burnett, Leonid A. Serebryannyy, Bob C. Lin, Zohar E. Ziff, Erin Maule, Robin Carroll, Mursal Naisan, Yogita Jethmalani, Laurent Pessaint, John-Paul M. Todd, Nicole A. Doria-Rose, James Brett Case, Igor P. Dmitriev, Elena A. Kashentseva, Baoling Ying, Alan Dodson, Katelyn Kouneski, Sijy O’Dell, Bushra Wali, Madison Ellis, Sucheta Godbole, Farida Laboune, Amy R. Henry, I-Ting Teng, Danyi Wang, Lingshu Wang, Qiong Zhou, Serge Zouantchangadou, Alex Van Ry, Mark G. Lewis, Hanne Andersen, Peter D. Kwong, David T. Curiel, Mario Roederer, Martha C. Nason, Kathryn E. Foulds, Mehul S. Suthar, Michael S. Diamond, Daniel C. Douek, Robert A. Seder
Journal: Nature Immunology (2024)

Abstract A mucosal route of vaccination could prevent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) replication at the site of infection and limit transmission. We compared protection against heterologous XBB.1.16 challenge in nonhuman primates (NHPs) ~5 months following intramuscular boosting with bivalent mRNA encoding WA1 and BA.5 spike proteins or mucosal boosting with a WA1–BA.5 bivalent chimpanzee adenoviral-vectored vaccine delivered by intranasal or aerosol device. NHPs boosted by either mucosal route had minimal virus replication in the nose and lungs, respectively. By contrast, protection by intramuscular mRNA was limited to the lower airways. The mucosally delivered vaccine elicited durable airway IgG and IgA responses and, unlike the intramuscular mRNA vaccine, induced spike-specific B cells in the lungs. IgG, IgA and T cell responses correlated with protection in the lungs, whereas mucosal IgA alone correlated with upper airway protection. This study highlights differential mucosal and serum correlates of protection and how mucosal vaccines can durably prevent infection against SARS-CoV-2.
A protein expression atlas on tissue samples and cell lines from cancer patients provides insights into tumor heterogeneity and dependencies
Authors: Jun Li, Wei Liu, Kamalika Mojumdar, Hong Kim, Zhicheng Zhou, Zhenlin Ju, Shwetha V. Kumar, Patrick Kwok-Shing Ng, Han Chen, Michael A. Davies, Yiling Lu, Rehan Akbani, Gordon B. Mills, Han Liang
Journal: Nature Cancer (2024)
Fratricide-resistant CD7-CAR T cells in T-ALL
Authors: Bernice L Z Oh, Noriko Shimasaki, Elaine Coustan-Smith, Esther Chan, Limei Poon, Shawn H R Lee, Frances Yeap, Lip Kun Tan, Louis Y A Chai, Nina Le Bert, Nicole Tan, Antonio Bertoletti, Siew Peng Chen, Francesca Del Bufalo, Marco Becilli, Franco Locatelli, Allen E J Yeoh, Dario Campana
Journal: Nature Medicine (2024)