tbuckley/cabot-search huggingface dataset:
Age at First Fracture and Later Fracture Risk in Older Adults Undergoing Osteoporosis Assessment
Authors: Carrie Ye, Suzanne N. Morin, Lisa M. Lix, Eugene V. McCloskey, Helena Johansson, Nicholas C. Harvey, John A. Kanis, William D. Leslie
Journal: JAMA Network Open (2024)

Importance Fragility fractures are often defined as those that occur after a certain age (eg, 40-50 years). Whether fractures occurring in early adulthood are equally associated with future fractures is unclear. Objective To examine whether the age at which a prior fracture occurred is associated with future fracture risk. Design, Setting, and Participants This observational, population-based cohort study included individuals from the Manitoba Bone Mineral Density Registry with a first bone mineral density (BMD) measurement between January 1, 1996, and March 31, 2018, with and without prior fracture in adulthood. Data analysis was completed between April 1, and May 31, 2023. Exposure Individuals with fractures before their first dual-energy x-ray absorptiometry were stratified by the age at first fracture (10-year intervals from 20-29 to ≥80 years of age). Main Outcomes and Measures Incident fractures occurring after dual-energy x-ray absorptiometry (index date) and before March 31, 2021, were identified using linked provincial administrative health data. Results The cohort included 88 696 individuals (80 066 [90.3%] female; mean [SD] age, 64.6 [11.0] years) with a mean (SD) femoral neck T score of −1.4 (1.0). A total of 21 105 individuals (23.8%) had sustained a prior fracture at a mean (SD) age of 57.7 (13.6) years (range, 20.0-102.4 years) at the time of first prior fracture. During a mean (SD) of 9.0 (5.5) years of follow-up, incident fractures occurred in 13 239 individuals (14.6%), including 12 425 osteoporotic fractures (14.0%), 9440 major osteoporotic fractures (MOFs) (10.6%), and 3068 hip fractures (3.5%). The sex- and age-adjusted hazard ratios for all incident fractures, osteoporotic fractures, and MOFs, according to age at first fracture, were all significantly elevated, with point estimates ranging from 1.55 (95% CI, 1.28-1.88) to 4.07 (95% CI, 2.99-5.52). After adjusting for the additional covariates, the effect estimates were similar and remained significantly elevated, with point estimates ranging from fully adjusted hazard ratios of 1.51 (95% CI, 1.42-1.60) to 2.12 (95% CI, 1.67-2.71) across age categories. Sensitivity analyses examining age at last prior fracture and in those with multiple prior fractures showed similar results. Conclusions and Relevance In this cohort study, fractures in adulthood were associated with future fractures regardless of the age at which they occurred. Thus, fractures in early adulthood should not be excluded when assessing an individual’s ongoing fracture risk.
Endometriosis and Ovarian Cancer
Authors: Kathryn L. Terry, Holly R. Harris, Stacey A. Missmer
Journal: JAMA (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 HomeNew OnlineCurrent IssueFor Authors JAMA+ AI 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Respiratory Benefits of Multisetting Air Purification in Children
Authors: Jian Lei, Qinghua Sun, Renjie Chen, Yixiang Zhu, Lu Zhou, Xiaowei Xue, Jianlong Fang, Yanjun Du, Yanwen Wang, Tiantian Li, Haidong Kan
Journal: JAMA Pediatrics (2024)

Importance Particulate matter exposure has been linked to impaired respiratory health in children, but the respiratory benefits of air purification have not been fully elucidated. Objectives To assess the respiratory health outcomes among children exposed to multisetting air purification vs sham purification. Design, Setting, and Participants This cluster randomized, double-blind, crossover trial was conducted among healthy school-aged children (10-12 years) in China from April to December 2021. Data were analyzed from December 2021 to July 2024. Interventions A multisetting (both in classrooms and bedrooms) air purification intervention compared with sham purification in a 2-stage intervention with more than 2 months (76 days) for each period and a washout period (88 days) to estimate the respiratory benefits of air purification. Main Outcomes and Measures The primary outcomes were pulmonary function, airway inflammation markers, and metabolites in exhaled breath condensate (EBC) before and after the air purification intervention. Linear mixed-effects models were used to estimate the respiratory benefits of children related to air purification. Differential metabolites in EBC were identified using metabolomics analysis to explore their possible mediation roles. Results A total of 79 children (38 male [48%]; mean [SD] age, 10.3 [0.5] years) were included in the statistical analyses. During the study period, the mean (SD) concentration of outdoor fine particulate matter (PM 2.5 ) at the school site was 32.53 (24.06) μg/m 3 . The time-weighted personal PM 2.5 concentration decreased by 45.14% during the true air purification period (mean [SD], 21.49 [8.72] μg/m 3 ) compared with the sham air purification period (mean [SD], 39.17 [14.25] μg/m 3 ). Air purification improved forced expiratory volume in 1 second by 8.04% (95% CI, 2.15%-13.93%), peak expiratory flow by 16.52% (95% CI, 2.76%-30.28%), forced vital capacity (FVC) by 5.73% (95% CI, 0.48%-10.98%), forced expiratory flow at 25% to 75% of FVC by 17.22% (95% CI, 3.78%-30.67%), maximal expiratory flow at 75% of FVC by 14.60% (95% CI, 0.35%-28.85%), maximal expiratory flow at 50% of FVC by 17.86% (95% CI, 3.65%-32.06%), and maximal expiratory flow at 25% of FVC by 18.22% (95% CI, 1.73%-34.70%). Fractional exhaled nitric oxide in the true air purification group decreased by 22.38% (95% CI, 2.27%-42.48%). Several metabolites in EBC (eg, L-tyrosine and β-alanine) were identified to mediate the effect of air purification on respiratory health. Conclusions and Relevance This randomized clinical trial provides robust and holistic evidence that indoor air purification notably improved pulmonary health in children, highlighting the importance of intensified indoor air purification in regions with high air pollution levels. Trial Registration ClinicalTrials.gov Identifier: NCT04835337 .
Drug Prices Negotiated by Medicare vs US Net Prices and Prices in Other Countries
Authors: Olivier J. Wouters, Sean D. Sullivan, Emma M. Cousin, Nico Gabriel, Irene Papanicolas, Inmaculada Hernandez
Journal: JAMA (2024)

This study analyzes how prices negotiated by Medicare in the US compare with net prices before negotiation, ceiling prices, and list prices in 6 other high-income countries.
Optimizing Care Planning for Older Adults in Primary Care
Authors: Jasmine Santoyo-Olsson, Lingsheng Li, Krista L. Harrison
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 JAMA+ AI 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
Targeted Maternal Chagas Disease Screening Among Individuals Born in a Chagas-Endemic Country
Authors: Alvaro Proaño, Neil C. Shah, Sneider A. Gutierrez Guarnizo, Monica Miranda-Schaeubinger, Michael Z. Levy, Robert H. Gilman, Dustin D. Flannery
Journal: JAMA Network Open (2024)

This cohort study examines the prevalence of Chagas disease among Hispanic pregnant women delivering in Philadelphia, Pennsylvania.
Conditional cash transfers and mortality in people hospitalised with psychiatric disorders: A cohort study of the Brazilian Bolsa Família Programme
Authors: Camila Bonfim, Flávia Alves, Érika Fialho, John A. Naslund, Maurício L. Barreto, Vikram Patel, Daiane Borges Machado
Journal: PLoS Medicine (2024)

Background Psychiatric patients experience lower life expectancy compared to the general population. Conditional cash transfer programmes (CCTPs) have shown promise in reducing mortality rates, but their impact on psychiatric patients has been unclear. This study tests the association between being a Brazilian Bolsa Família Programme (BFP) recipient and the risk of mortality among people previously hospitalised with any psychiatric disorders. Methods and findings This cohort study utilised Brazilian administrative datasets, linking social and health system data from the 100 Million Brazilian Cohort, a population-representative study. We followed individuals who applied for BFP following a single hospitalisation with a psychiatric disorder between 2008 and 2015. The outcome was mortality and specific causes, defined according to International Classification of Diseases 10th Revision (ICD-10). Cox proportional hazards models estimated the hazard ratio (HR) for overall mortality and competing risks models estimated the HR for specific causes of death, both associated with being a BFP recipient, adjusted for confounders, and weighted with a propensity score. We included 69,901 psychiatric patients aged between 10 and 120, with the majority being male (60.5%), and 26,556 (37.99%) received BFP following hospitalisation. BFP was associated with reduced overall mortality (HR 0.93, 95% CI 0.87,0.98, p 0.018) and mortality due to natural causes (HR 0.89, 95% CI 0.83, 0.96, p &lt; 0.001). Reduction in suicide (HR 0.90, 95% CI 0.68, 1.21, p = 0.514) was observed, although it was not statistically significant. The BFP’s effects on overall mortality were more pronounced in females and younger individuals. In addition, 4% of deaths could have been prevented if BFP had been present (population attributable risk (PAF) = 4%, 95% CI 0.06, 7.10). Conclusions BFP appears to reduce mortality rates among psychiatric patients. While not designed to address elevated mortality risk in this population, this study highlights the potential for poverty alleviation programmes to mitigate mortality rates in one of the highest-risk population subgroups.
Autonomic Dysfunction and Inflammation in CKD
Authors: Carmine Zoccali, Francesca Mallamaci, Mehmet Kanbay, Evangelia Dounousi, Peter Kotanko, Joachim Jankowski, Glenn M. Chertow
Journal: Journal of the American Society of Nephrology (2024)

Zoccali, Carmine; Mallamaci, Francesca; Kanbay, Mehmet; Dounousi, Evangelia; Kotanko, Peter; Jankowski, Joachim; Chertow, Glenn M. Author Information
EpiCHAOS: a metric to quantify epigenomic heterogeneity in single-cell data
Authors: Katherine Kelly, Michael Scherer, Martina Maria Braun, Pavlo Lutsik, Christoph Plass
Journal: Genome biology (2024)

Abstract Epigenetic heterogeneity is a fundamental property of biological systems and is recognized as a potential driver of tumor plasticity and therapy resistance. Single-cell epigenomics technologies have been widely employed to study epigenetic variation between—but not within—cellular clusters. We introduce epiCHAOS: a quantitative metric of cell-to-cell heterogeneity, applicable to any single-cell epigenomics data type. After validation in synthetic datasets, we apply epiCHAOS to investigate global and region-specific patterns of epigenetic heterogeneity across diverse biological systems. EpiCHAOS provides an excellent approximation of stemness and plasticity in development and malignancy, making it a valuable addition to single-cell cancer epigenomics analyses.
Chromatin loops gather targets of upstream regulators together for efficient gene transcription regulation during vernalization in wheat
Authors: Yanyan Liu, Xintong Xu, Chao He, Liujie Jin, Ziru Zhou, Jie Gao, Minrong Guo, Xin Wang, Chuanye Chen, Mohammed H Ayaad, Xingwang Li, Wenhao Yan
Journal: Genome biology (2024)
Novel tri-specific T-cell engager targeting IL-13Rα2 and EGFRvIII provides long-term survival in heterogeneous GBM challenge and promotes antitumor cytotoxicity with patient immune cells
Authors: Daniel H Park, Pratik S Bhojnagarwala, Kevin Liaw, Devivasha Bordoloi, Nicholas J Tursi, Shushu Zhao, Zev A Binder, Donald O'Rourke, David B Weiner
Journal: Journal for ImmunoTherapy of Cancer (2024)

Background Glioblastoma multiforme (GBM) is known for its high antigenic heterogeneity, which undermines the effectiveness of monospecific immunotherapies. Multivalent immunotherapeutic strategies that target multiple tumor antigens simultaneously could enhance clinical outcomes by preventing antigen-driven tumor escape mechanisms. Methods We describe novel trivalent antibodies, DNA-encoded tri-specific T-cell engagers (DTriTEs), targeting two GBM antigens, epidermal growth factor receptor variant III (EGFRvIII) and IL-13Rα2, and engaging T cells through CD3. We engineered three DTriTE constructs, each with a unique arrangement of the antigen-binding fragments within a single-chain sequence. We assessed the binding efficiency and cytotoxic activity of these DTriTEs in vitro on target cells expressing relevant antigens. In vivo efficacy was tested in immunocompromised mice, including a longitudinal expression study post-administration and a survival analysis in an NOD scid gamma (NSG)-K mouse model under a heterogeneous tumor burden. RNA sequencing of DTriTE-activated T cells was employed to identify the molecular pathways influenced by the treatment. The antitumor cytotoxicity of patient-derived immune cells was evaluated following stimulation by DTriTE to assess its potential effectiveness in a clinical setting. Results All DTriTE constructs demonstrated strong binding to EGFRvIII and IL-13Rα2-expressing cells, induced significant T cell-mediated cytotoxicity, and enhanced cytokine production (interferon-γ, tumor necrosis factor (TNF)-α, and interleukin(IL)-2). The lead construct, DT2035, sustained expression for over 105 days in vivo and exhibited elimination of tumor burden in a heterogeneous intracranial GBM model, outperforming monospecific antibody controls. In extended survival studies using the NSG-K model, DT2035 achieved a 67% survival rate over 120 days. RNA sequencing of DTriTE-activated T cells showed that DT2035 enhances genes linked to cytotoxicity, proliferation, and immunomodulation, reflecting potent immune activation. Finally, DT2035 effectively induced target-specific cytotoxicity in post-treatment peripheral blood mononuclear cells from patients with GBM, highlighting its potential for clinical effectiveness. Conclusions DTriTEs exhibit potent anti-tumor effects and durable in vivo activity, offering promising therapeutic potential against GBM. These findings support further development of such multivalent therapeutic strategies to improve treatment outcomes in GBM and potentially other antigenically heterogeneous tumors. The opportunity to advance such important therapies either through biologic delivery or direct in vivo nucleic acid production is compelling.
Enhanced prefrontal nicotinic signaling as evidence of active compensation in Alzheimer’s disease models
Authors: Saige K. Power, Sridevi Venkatesan, Sarah Qu, JoAnne McLaurin, Evelyn K. Lambe
Journal: Translational Neurodegeneration (2024)

Abstract Background Cognitive reserve allows for resilience to neuropathology, potentially through active compensation. Here, we examine ex vivo electrophysiological evidence for active compensation in Alzheimer’s disease (AD) focusing on the cholinergic innervation of layer 6 in prefrontal cortex. Cholinergic pathways are vulnerable to neuropathology in AD and its preclinical models, and their modulation of deep layer prefrontal cortex is essential for attention and executive function. Methods We functionally interrogated cholinergic modulation of prefrontal layer 6 pyramidal neurons in two preclinical models: a compound transgenic AD mouse model that permits optogenetically-triggered release of endogenous acetylcholine and a transgenic AD rat model that closely recapitulates the human trajectory of AD. We then tested the impact of therapeutic interventions to further amplify the compensated responses and preserve the typical kinetic profile of cholinergic signaling. Results In two AD models, we found potentially compensatory upregulation of functional cholinergic responses above non-transgenic controls after onset of pathology. To identify the locus of this enhanced cholinergic signal, we dissected key pre- and post-synaptic components with pharmacological strategies. We identified a significant and selective increase in post-synaptic nicotinic receptor signalling on prefrontal cortical neurons. To probe the additional impact of therapeutic intervention on the adapted circuit, we tested cholinergic and nicotinic-selective pro-cognitive treatments. Inhibition of acetylcholinesterase further enhanced endogenous cholinergic responses but greatly distorted their kinetics. Positive allosteric modulation of nicotinic receptors, by contrast, enhanced endogenous cholinergic responses and retained their rapid kinetics. Conclusions We demonstrate that functional nicotinic upregulation occurs within the prefrontal cortex in two AD models. Promisingly, this nicotinic signal can be further enhanced while preserving its rapid kinetic signature. Taken together, our work suggests that compensatory mechanisms are active within the prefrontal cortex that can be harnessed by nicotinic receptor positive allosteric modulation, highlighting a new direction for cognitive treatment in AD neuropathology.
Cancer care and outreach in South Asian Association for Regional Cooperation (SAARC) countries: from epidemiology and the National Cancer Control Programme to screening, diagnosis, and treatment
Authors: M Saiful Huq, Sandhya C Acharya, Susmita Sharma, Saugat Poudyal, Simit Sapkota, Sunil Shrestha, Manish Gautam, Sudhir R Silwal, Mohammad M Haque, A F M Kamal Uddin, Sanjeeva Gunasekara, K Govind Babu, Ugyen Tshomo, Ahmad J Safi, Ahmed I Masood, Mostafa A Sumon, Mohammad A Hai, Altaf Hossain, Shaila Purvin, Heath Devin Skinner, Stephen Avery, Wilfred Ngwa, Krishni Wijesooriya
Journal: The Lancet Oncology (2024)
Clinical, Immunologic, and Genetic Characteristics in Patients with Syndrome of Undifferentiated Recurrent Fevers (<scp>SURF</scp>)
Authors: Marci Macaraeg, Elizabeth Baker, Elizabeth Handorf, Michael Matt, Elizabeth K Baker, Hermine Brunner, Alexei A Grom, Michael Henrickson, Jennifer Huggins, Wenying Zhang, Pui Lee, Rebecca Marsh, Grant S. Schulert
Journal: Arthritis & Rheumatology (2024)

Background/Statement of Purpose Syndrome of Undifferentiated Recurrent Fevers (SURF) is characterized by recurrent fevers and autoinflammation without a confirmed molecular diagnosis of a Hereditary Recurrent Fever syndrome (HRF), and not fulfilling criteria for Periodic Fever, Adenitis, Pharyngitis, Aphthous stomatitis syndrome (PFAPA). The goal of this study was to characterize clinical features of SURF patients compared to PFAPA, and to analyze their cytokine signature, genetic variations, and responses to treatment. Methods We enrolled 46 patients followed at Cincinnati Children's Hospital Medical Center. Baseline data and inflammatory cytokines were collected at enrollment, and their clinical course was followed. Cytokine analysis was performed using a cytokine multiplex assay. Many patients had specific or whole exome genetic testing. Results The prevalence of rash and arthralgias were higher in SURF compared to PFAPA. Pharyngitis and adenopathy were less frequent. A subset of SURF patients clustered together with elevated pro‐inflammatory cytokines and more frequently required biologic therapy. Focused analysis of WES data revealed that variants of unknown clinical significance (VUCS) were frequently identified in genes implicated in B cell development, immunodeficiencies, and inflammatory bowel disease risk. Treatments for SURF patients commonly included on‐demand steroids, colchicine, and anti‐IL1 therapy. Conclusion Our findings suggest SURF is a heterogeneous group but has distinct clinical and immunologic features from disorders like PFAPA. Patients have frequent VUCS, which may have relevance to disease pathogenesis. A subset of patients showed more inflammation and increased need for biologic use. Further research is necessary to define whether there exist distinct SURF endotypes and to better predict treatment outcomes.
A super soft thermoplastic biodegradable elastomer with high elasticity for arterial regeneration
Authors: Yating Jia, Xin Xu, Hao Lu, Kanwal Fatima, Yali Zhang, Haibo Du, Jin Yang, Xiaojun Zhou, Xiaofeng Sui, Lei Hou, Yanan Pang, Chuanglong He
Journal: Biomaterials (2024)
Cancer research in South Asian Association for Regional Cooperation (SAARC) countries
Authors: M Saiful Huq, Sandhya C Acharya, Manish Gautam, Sudhir R Silwal, Simit Sapkota, Saugat Poudyal, Susmita Sharma, K Govind Babu, Taslima Nigar, Shahana Pervin, Seema Gulia, Sanjeeva Gunasekara, A F M Kamal Uddin, Ugyen Tshomo, Ahmad J Safi, Mohammad S Nadeem, Ahmed I Masood, Mostafa A Sumon, Shaila Purvin, Mohammad A Hai, Heath Devin Skinner, Stephen Avery, Wilfred Ngwa, Krishni Wijesooriya
Journal: The Lancet Oncology (2024)
Cancer care and outreach in the South Asian Association for Regional Cooperation (SAARC) region: overcoming barriers and addressing challenges
Authors: M Saiful Huq, Sandhya C Acharya, Saugat Poudyal, Susmita Sharma, Sudhir R Silwal, Simit Sapkota, Manish Gautam, Mohammad M Haque, A F M Kamal Uddin, Sanjeeva Gunasekara, K Govind Babu, Ugyen Tshomo, Ahmad J Safi, Ahmed I Masood, Mostafa A Sumon, Shaila Purvin, Mohammad A Hai, Heath Devin Skinner, Stephen Avery, Wilfred Ngwa, Krishni Wijesooriya
Journal: The Lancet Oncology (2024)
Cancer education and training within the South Asian Association for Regional Cooperation (SAARC) countries
Authors: M Saiful Huq, Sandhya C Acharya, Simit Sapkota, Sudhir R Silwal, Manish Gautam, Susmita Sharma, Saugat Poudyal, Mostafa A Sumon, Tasneem Hossain, A F M Kamal Uddin, Sanjeeva Gunasekara, K Govind Babu, Hemant Malhotra, Ugyen Tshomo, Ahmad J Safi, Ahmed I Masood, Shaila Purvin, Mohammad A Hai, Syed MA Islam, Towhidul Islam, Heath Devin Skinner, Stephen Avery, Wilfred Ngwa, Krishni Wijesooriya
Journal: The Lancet Oncology (2024)