tbuckley/cabot-search huggingface dataset:
Incidence of Cancer and Cardiovascular Disease After Bariatric Surgery in Older Patients
Authors: Peter Gerber, David Naqqar, My von Euler-Chelpin, Joonas H. Kauppila, Giola Santoni, Dag Holmberg
Journal: JAMA Network Open (2024)

Importance Bariatric surgery is associated with decreased risk of obesity-related cancer and cardiovascular disease but is typically reserved for patients younger than 60 years. Whether these associations hold for patients who undergo surgery at older ages is uncertain. Objective To determine whether bariatric surgery is associated with a decreased risk of obesity-related cancer and cardiovascular disease in patients who underwent surgery at age 60 years or older. Design, Setting, and Participants Population-based cohort study of patients from Denmark, Finland, and Sweden who underwent bariatric surgery at age 60 years or older without previous malignant neoplasm or cardiovascular disease between 1989 and 2019. Each patient who underwent surgery was exactly matched to 5 patients with nonoperative treatment for obesity of the same country, sex, and age at the date of surgery. Data were analyzed in December 2023. Exposure Receiving treatment for obesity, including bariatric surgery and nonoperative treatments. Main Outcomes and Measures The main outcome was obesity-related cancer, defined as a composite outcome of breast, endometrial, esophageal, colorectal, and kidney cancer, identified from the national cancer registries. The secondary outcome was cardiovascular disease, defined as a composite outcome of myocardial infarction, ischemic stroke, and cerebral hemorrhage, identified from the patient registries. Multivariable Cox regression provided hazard ratios (HR) with 95% CIs adjusted for diabetes, hypertension, peripheral vascular disease, chronic obstructive pulmonary disease, kidney disease, and frailty. Results In total, 15 300 patients (median [IQR] age, 63 [61-65] years; 10 152 female patients [66.4%]) were included, of which 2550 (16.7%) had bariatric surgery at age 60 or older and 12 750 (83.3%) had nonoperative treatment. During a median (IQR) of 5.8 (2.8-8.5) person-years of follow-up, 658 (4.3%) developed obesity-related cancer and 1436 (9.4%) developed cardiovascular disease. The risk of obesity-related cancer (HR, 0.81; 95% CI, 0.64-1.03) and cardiovascular disease (HR, 0.86; 95% CI, 0.74-1.01) were similar among who underwent surgery and those who did not. Gastric bypass (1930 patients) was associated with a decreased risk of obesity-related cancer (71 patients [3.7%]; HR, 0.74; 95% CI, 0.56-0.97) and cardiovascular disease (159 patients [8.2%]; HR, 0.82; 95% CI, 0.69-0.99) compared with matched controls (9650 patients; obesity-related cancer: 442 patients [4.6%]; cardiovascular disease: 859 patients [8.9%]). Conclusions and Relevance This cohort study found that bariatric surgery in older patients is not associated with lower rates of obesity-related cancer and cardiovascular events, but there was evidence that gastric bypass may be associated with lower risk of both outcomes.
Interleukin-2 family cytokines IL-9 and IL-21 differentially regulate innate and adaptive type 2 immunity in asthma
Authors: Fabian Bick, Claudia M Brenis Gómez, Inés Lammens, Justine Van Moorleghem, Caroline De Wolf, Sam Dupont, Laure Dumoutier, Neal P Smith, Alexandra-Chloé Villani, Robin Browaeys, Jehan Alladina, Alexis M Haring, Benjamin D Medoff, Josalyn L Cho, René Bigirimana, Joao Vieira, Hamida Hammad, Christophe Blanchetot, Martijn J Schuijs, Bart N Lambrecht
Journal: Journal of Allergy and Clinical Immunology (2024)

Asthma is often accompanied by type 2 immunity rich in IL-4, IL-5, and IL-13 cytokines produced by T
Genetic and functional analysis of Raynaud’s syndrome implicates loci in vasculature and immunity
Authors: Anniina Tervi, Markus Ramste, Erik Abner, Paul Cheng, Jacqueline M Lane, Matthew Maher, Jesse Valliere, Vilma Lammi, Satu Strausz, Juha Riikonen, Trieu Nguyen, Gabriella E Martyn, Maya U Sheth, Fan Xia, Mauro Lago Docampo, Wenduo Gu, Tõnu Esko, Richa Saxena, Matti Pirinen, Aarno Palotie, Samuli Ripatti, Nasa Sinnott-Armstrong, Mark Daly, Jesse M Engreitz, Marlene Rabinovitch, Caroline A Heckman, Thomas Quertermous, Samuel E Jones, Hanna M Ollila
Journal: Cell Genomics (2024)

Raynaud's syndrome is a dysautonomia where exposure to cold causes vasoconstriction and hypoxia, particularly in the extremities. We performed meta-analysis in four cohorts and discovered eight loci (ADRA2A, IRX1, NOS3, ACVR2A, TMEM51, PCDH10-DT, HLA, and RAB6C) where ADRA2A, ACVR2A, NOS3, TMEM51, and IRX1 co-localized with expression quantitative trait loci (eQTLs), particularly in distal arteries. CRISPR gene editing further showed that ADRA2A and NOS3 loci modified gene expression and in situ RNAscope clarified the specificity of ADRA2A in small vessels and IRX1 around small capillaries in the skin. A functional contraction assay in the cold showed lower contraction in ADRA2A-deficient and higher contraction in ADRA2A-overexpressing smooth muscle cells. Overall, our study highlights the power of genome-wide association testing with functional follow-up as a method to understand complex diseases. The results indicate temperature-dependent adrenergic signaling through ADRA2A, effects at the microvasculature by IRX1, endothelial signaling by NOS3, and immune mechanisms by the HLA locus in Raynaud's syndrome.
Smartwatch Measures of Outdoor Exposure and Myopia in Children
Authors: Jun Chen, Jingjing Wang, Ziyi Qi, Shang Liu, Lingyi Zhao, Bo Zhang, Kaige Dong, Linlin Du, Jinliuxing Yang, Haidong Zou, Xiangui He, Xun Xu
Journal: JAMA Network Open (2024)

Importance Time spent outdoors has been proven effective in preventing myopia, but little is known about the association of outdoor exposure patterns with myopia. Objective To examine the association of outdoor exposure patterns with myopic shift in children. Design, Setting, and Participants This 1-year prospective cohort study from December 2017 to December 2018 was a secondary analysis of a cluster-randomized trial (Shanghai Time Outside to Reduce Myopia [STORM]). STORM was a school-based intervention study, recruiting 16 schools from 8 districts in Shanghai, from October 2016 to December 2018. Children without myopia at baseline who consistently wore a smartwatch for a minimum of 6 hours daily, sustained for at least 90 days, and who had complete information were included. Data analysis was performed from December 2017 to December 2018. Exposures The outdoor exposure pattern was defined as the episode of time outdoors and instant sunlight intensity over a continuous period. Main Outcomes and Measures Myopic shift was defined as the absolute change in refraction between the initial spherical equivalence and the follow-up spherical equivalence. Results This study included 2976 students (mean [SD] age, 7.2 [0.6] years; 1525 girls [51.2%]). The mean (SD) daily time outdoors was 90 (28) minutes, and the mean (SD) sunlight intensity was 2345 (486) lux. Of the 12 outdoor exposure patterns, the major outdoor exposure patterns were time outdoors with at least 15 minutes, accounting for 74.9% of minutes (33 677 584 of 45 016 800 minutes). Only patterns with at least 15 minutes accompanied with no less than 2000 lux were associated with less myopic shift in refraction (for ≥15 minutes and 2000 to 3999 lux, −0.007 diopter [D] [95% CI, −0.011 to −0.002 D]; for ≥15 minutes and ≥4000 lux, −0.006 D [95% CI, −0.010 to −0.002 D]). The isotemporal substitution of patterns with at least 15 minutes and 2000 lux for other outdoor exposure patterns was positively associated with less myopic shift. Conclusions and Relevance In this 1-year prospective cohort study of children with smartwatches, continuous outdoor exposure with at least 15 minutes accompanied with no less than 2000 lux sunlight intensity was associated with less myopic shift. These findings suggest that future outdoor interventions should focus not only on the overall time outdoors but also on the effective outdoor exposure patterns, as a means to effectively prevent myopia in children.
Benchmarking Emergency Physician EHR Time per Encounter Based on Patient and Clinical Factors
Authors: Mark S. Iscoe, Arjun K. Venkatesh, Margaret L. Holland, Harlan M. Krumholz, Karen Dorsey Sheares, Edward R. Melnick
Journal: JAMA Network Open (2024)

This cross-sectional study assesses the associations between patient and clinical factors and variations in time emergency department physicians spend using electronic health record (EHR) systems.
Reporting on data sharing: executive position of the EQUATOR Network
Authors: David Moher, Gary Collins, Tammy Hoffmann, Paul Glasziou, Philippe Ravaud, Zhao-Xiang Bian
Journal: BMJ (2024)

The EQUATOR (Enhancing the Quality and Transparency Of health Research) Network supports the practice of data sharing, and the reporting of data management and sharing plans, in all reports of biomedical research. Both practices should be included as checklist items when developing new or updating reporting guidelines. More focus should be given to structuring and standardising data management and sharing plans to help provide a similar impact as reporting guidelines.
Exploration of Electronic Health Record Patterns of Emergency Physicians—Charting the Digital Burden
Authors: Lisa S. Rotenstein, Melanie Molina
Journal: JAMA Network Open (2024)

Mark S. Iscoe, MD, MHS; Arjun K. Venkatesh, MD, MBA, MHS; Margaret L. Holland, PhD, MPH; Harlan M. Krumholz, MD, SM; Karen Dorsey Sheares, MD, PhD; Edward R. Melnick, MD, MHS
National age-specific mortality trends for cervical and breast cancers in urban–rural areas of China from 2009 to 2021: a population-based analysis
Authors: Meng-Long Li, Jin-Lei Qi, Ya-Qi Ma, Wen Shu, Hui-Di Xiao, Li-Jun Wang, Peng Yin, Hao-Yan Guo, Sten H. Vermund, Mai-Geng Zhou, Yi-Fei Hu
Journal: Military Medical Research (2024)

Abstract Background Cervical and breast cancers are among the top 4 leading causes of cancer-related mortality in women. This study aimed to examine age-specific temporal trends in mortality for cervical and breast cancers in urban and rural areas of China from 2009 to 2021. Methods Age-specific mortality data for cervical and breast cancers among Chinese women aged 20–84 years were obtained from China’s National Disease Surveillance Points system spanning the years 2009 to 2021. Negative binomial regression models were utilized to assess urban–rural differences in mortality rate ratios, while Joinpoint models with estimated average annual percent changes (AAPC) and slopes were employed to compare temporal trends and the acceleration of mortality rates within different age groups. Results From 2009 to 2021, there was a relative increase in age-specific mortality associated with the two cancers observed in rural areas compared with urban areas. A rising trend in the screening age of 35–64 [AAPC: 4.0%, 95% confidence interval (CI) 0.5–7.6%, P = 0.026] for cervical cancer was noted in rural areas, while a stable trend (AAPC: − 0.7%, 95% CI − 5.8 to 4.6%, P = 0.78) was observed in urban areas. As for breast cancer, a stable trend (AAPC: 0.3%, 95% CI − 0.3 to 0.9%, P = 0.28) was observed in rural areas compared to a decreasing trend (AAPC: − 2.7%, 95% CI − 4.6 to − 0.7%, P = 0.007) in urban areas. Urban–rural differences in mortality rates increased over time for cervical cancer but decreased for breast cancer. Mortality trends for both cervical and breast cancers showed an increase with age across 4 segments, with the most significant surge in mortality observed among the 35–54 age group across urban and rural areas, periods, and regions in China. Conclusions Special attention should be given to women aged 35–54 years due to mortality trends and rural–urban disparities. Focusing on vulnerable age groups and addressing rural–urban differences in the delivery of cancer control programs can enhance resource efficiency and promote health equity.
Laterality, heterotaxy, and isolated congenital heart defects
Authors: Carolina Putotto, Flaminia Pugnaloni, Marta Unolt, Giulio Calcagni, Paolo Versacci, Bruno Marino
Journal: Genome Medicine (2024)

To date, the role of NODAL in normal and abnormal L-R asymmetry has been well established. In a recent paper, mutations of this gene have been reported in heterotaxy but also in transposition with D- or L-ventricular loop. The effects of NODAL and other laterality genes can be recognized separately in all three cardiac segments: for topology and septation of the atria, for ventricular looping, and for spiralization and alignment of the great arteries.
Patient-Reported Outcome Measures Help Patients With Cancer
Authors: Michael J. Hassett, Christine Cronin
Journal: JAMA Network Open (2024)

Amaris K. Balitsky, MD, MSc; Daniel Rayner, BHSc; Joanne Britto, MD; Anath C. Lionel, MD, PhD; Lydia Ginsberg, MD; Wanjae Cho, MD; Ann Mary Wilfred, BHSc; Huda Sardar, BHSc; Nathan Cantor, MD, MSc; Hira Mian, MD; Mark N. Levine, MD, MSc; Gordon H. Guyatt, MD, MSc
Loss of Dnajc21 leads to cytopenia and altered nucleotide metabolism in zebrafish
Authors: Sarada Ketharnathan, Sujata Pokharel, Sergey V. Prykhozhij, Anna Cordeiro-Santanach, Kevin Ban, Serkan Dogan, Huy-Dung Hoang, Mira F. Liebman, Elaine Leung, Tommy Alain, Irina Alecu, Steffany A. L. Bennett, Miroslava Čuperlović-Culf, Yigal Dror, Jason N. Berman
Journal: Leukemia (2024)

Mutations in the DNAJC21 gene were recently described in Shwachman–Diamond syndrome (SDS), a bone marrow failure syndrome with high predisposition for myeloid malignancies. To study the underlying biology in hematopoiesis regulation and disease, we generated the first in vivo model of Dnajc21 deficiency using the zebrafish. Zebrafish dnajc21 mutants phenocopy key SDS patient phenotypes such as cytopenia, reduced growth, and defective protein synthesis. We show that cytopenia results from impaired hematopoietic differentiation, accumulation of DNA damage, and reduced cell proliferation. The introduction of a biallelic tp53 mutation in the dnajc21 mutants leads to the development of myelodysplastic neoplasia-like features defined by abnormal erythroid morphology and expansion of hematopoietic progenitors. Using transcriptomic and metabolomic analyses, we uncover a novel role for Dnajc21 in nucleotide metabolism. Exogenous nucleoside supplementation restores neutrophil counts, revealing an association between nucleotide imbalance and neutrophil differentiation, suggesting a novel mechanism in dnajc21-mutant SDS biology.
Accuracy, Consistency, and Hallucination of Large Language Models When Analyzing Unstructured Clinical Notes in Electronic Medical Records
Authors: Savyasachi V. Shah
Journal: JAMA Network Open (2024)

Kathryn G. Burford, PhD; Nicole G. Itzkowitz, MSc; Ashley G. Ortega, BSc; Julien O. Teitler, PhD; Andrew G. Rundle, DrPH
Microglia are not necessary for maintenance of blood-brain barrier properties in health, but PLX5622 alters brain endothelial cholesterol metabolism
Authors: Caterina P Profaci, Sean S Harvey, Kaja Bajc, Tony Z Zhang, Danielle A Jeffrey, Alexander Z Zhang, Kelsey M Nemec, Hayk Davtyan, Carleigh A O'Brien, Gabriel L McKinsey, Aaron Longworth, Timothy P McMullen, Joia K Capocchi, Jessica G Gonzalez, Devon A Lawson, Thomas D Arnold, Dimitrios Davalos, Mathew Blurton-Jones, Fabrice Dabertrand, F Chris Bennett, Richard Daneman
Journal: Neuron (2024)

Microglia, the resident immune cells of the central nervous system, are intimately involved in the brain's most basic processes, from pruning neural synapses during development to preventing excessive neuronal activity throughout life. Studies have reported both helpful and harmful roles for microglia at the blood-brain barrier (BBB) in the context of disease. However, less is known about microglia-endothelial cell interactions in the healthy brain. To investigate the role of microglia at a healthy BBB, we used the colony-stimulating factor 1 receptor (CSF1R) inhibitor PLX5622 to deplete microglia and analyzed the BBB ultrastructure, permeability, and transcriptome. Interestingly, we found that, despite their direct contact with endothelial cells, microglia are not necessary for the maintenance of BBB structure, function, or gene expression in the healthy brain. However, we found that PLX5622 treatment alters brain endothelial cholesterol metabolism. This effect was independent from microglial depletion, suggesting that PLX5622 has off-target effects on brain vasculature.
Integrative clinical and preclinical studies identify FerroTerminator1 as a potent therapeutic drug for MASH
Authors: Liang Tao, Xinquan Yang, Chaodong Ge, Peng Zhang, Wenjian He, Xingbo Xu, Xin Li, Wenteng Chen, Yingying Yu, Huai Zhang, Sui-Dan Chen, Xiao-Yan Pan, Yunxing Su, Chengfu Xu, Yongping Yu, Ming-Hua Zheng, Junxia Min, Fudi Wang
Journal: Cell Metabolism (2024)

The complex etiological factors associated with metabolic dysfunction-associated fatty liver disease (MAFLD), including perturbed iron homeostasis, and the unclear nature by which they contribute to disease progression have resulted in a limited number of effective therapeutic interventions. Here, we report that patients with metabolic dysfunction-associated steatohepatitis (MASH), a pathological subtype of MAFLD, exhibit excess hepatic iron and that it has a strong positive correlation with disease progression. FerroTerminator1 (FOT1) effectively reverses liver injury across multiple MASH models without notable toxic side effects compared with clinically approved iron chelators. Mechanistically, our multi-omics analyses reveal that FOT1 concurrently inhibits hepatic iron accumulation and c-Myc-Acsl4-triggered ferroptosis in various MASH models. Furthermore, MAFLD cohort studies suggest that serum ferritin levels might serve as a predictive biomarker for FOT1-based therapy in MASH. These findings provide compelling evidence to support FOT1 as a promising novel therapeutic option for all stages of MAFLD and for future clinical trials.
Error in Results and eTables 3 and 4
Journal: JAMA Network Open (2024)

Error in Results and eTables 3 and 4In the Original Investigation titled "Comparison of Vital Sign Cutoffs to Identify Children With Major Trauma," 1 published online February 16, 2024, an error in applying exlusion criteria for the validation sample resulted in incorrect measures of accuracy for the sample in the Results and in eTables 3 and 4 in Supplement 1.This article has been corrected. 1
Host–microbe serotonin metabolism
Authors: Emilia Nunzi, Marilena Pariano, Claudio Costantini, Enrico Garaci, Paolo Puccetti, Luigina Romani
Journal: Trends in Endocrinology and Metabolism (2024)

As a result of a long evolutionary history, serotonin plays a variety of physiological roles, including neurological, cardiovascular, gastrointestinal, and endocrine functions. While many of these activities can be accommodated within the serotoninergic activity, recent findings have revealed an unsuspected role of serotonin in orchestrating host and microbial dialogue at the tryptophan dining table, to the benefit of local and systemic homeostasis. Herein we review the dual role of serotonin at the host-microbe interface and discuss how unraveling the interconnections among the host and microbial pathways of tryptophan degradation may help to accommodate the versatility of serotonin in physiology and pathology.
Response to “Comment on ‘Evidence Synthesis of Observational Studies in Environmental Health: Lessons Learned from a Systematic Review on Traffic-Related Air Pollution’”
Authors: Hanna Boogaard, Richard W. Atkinson, Jeffrey R. Brook, Howard H. Chang, Gerard Hoek, Barbara Hoffmann, Sharon K. Sagiv, Evangelia Samoli, Audrey Smargiassi, Adam A. Szpiro, Danielle Vienneau, Jennifer Weuve, Frederick W. Lurmann, Francesco Forastiere
Journal: Environmental Health Perspectives (2024)
Corrigendum to “Bidirectional juxtacrine ephrinB2/Ephs signaling promotes angiogenesis of ECs and maintains self-renewal of MSCs” [Biomaterials 172 (2018) 1–13]
Authors: Cen Cao, Ying Huang, Qingming Tang, Chenguang Zhang, Lei Shi, Jiajia Zhao, Li Hu, Zhewen Hu, Yun Liu, Lili Chen
Journal: Biomaterials (2024)
The GC-content at the 5′ ends of human protein-coding genes is undergoing mutational decay
Authors: Yi Qiu, Yoon Mo Kang, Christopher Korfmann, Fanny Pouyet, Andrew Eckford, Alexander F Palazzo
Journal: Genome biology (2024)

Abstract Background In vertebrates, most protein-coding genes have a peak of GC-content near their 5′ transcriptional start site (TSS). This feature promotes both the efficient nuclear export and translation of mRNAs. Despite the importance of GC-content for RNA metabolism, its general features, origin, and maintenance remain mysterious. We investigate the evolutionary forces shaping GC-content at the transcriptional start site (TSS) of genes through both comparative genomic analysis of nucleotide substitution rates between different species and by examining human de novo mutations. Results Our data suggests that GC-peaks at TSSs were present in the last common ancestor of amniotes, and likely that of vertebrates. We observe that in apes and rodents, where recombination is directed away from TSSs by PRDM9, GC-content at the 5′ end of protein-coding gene is currently undergoing mutational decay. In canids, which lack PRDM9 and perform recombination at TSSs, GC-content at the 5′ end of protein-coding is increasing. We show that these patterns extend into the 5′ end of the open reading frame, thus impacting synonymous codon position choices. Conclusions Our results indicate that the dynamics of this GC-peak in amniotes is largely shaped by historic patterns of recombination. Since decay of GC-content towards the mutation rate equilibrium is the default state for non-functional DNA, the observed decrease in GC-content at TSSs in apes and rodents indicates that the GC-peak is not being maintained by selection on most protein-coding genes in those species.
How to manage patients with germline <i>DDX41</i> variants: Recommendations from the Nordic working group on germline predisposition for myeloid neoplasms
Authors: Panagiotis Baliakas, Bianca Tesi, Jörg Cammenga, Asbjørg Stray‐Pedersen, Kirsi Jahnukainen, Mette Klarskov Andersen, Helena Ågerstam, Maria Creignou, Ingunn Dybedal, Klas Raaschou‐Jensen, Kirsten Grønbæk, Outi Kilpivaara, Eva Hellström Lindberg, Ulla Wartiovaara‐Kautto
Journal: HemaSphere (2024)

Abstract Increasing recognition of germline DDX41 variants in patients with hematological malignancies prompted us to provide DDX41 ‐specific recommendations for diagnosis, surveillance, and treatment. Causative germline variants in the DDX41 predispose to the development of myeloid neoplasms (MNs), especially myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). Almost 3%–5% of all patients with MDS or AML carry a pathogenic or likely pathogenic germline DDX41 variant, while half of them acquire a somatic second hit in the other allele. DDX41 ‐associated MNs exhibit unique clinical characteristics compared to other hematological malignancies with germline predisposition: MNs occur mostly at advanced age and follow an indolent clinical course. Male carriers are more prone to develop MDS or AML than females. DDX41 ‐associated MN is often hypoplastic, and the malignancy may be preceded by cytopenias.
SynGAP: a synteny-based toolkit for gene structure annotation polishing
Authors: Fengqi Wu, Yingxiao Mai, Chengjie Chen, Rui Xia
Journal: Genome biology (2024)

Genome sequencing has become a routine task for biologists, but the challenge of gene structure annotation persists, impeding accurate genomic and genetic research. Here, we present a bioinformatics toolkit, SynGAP (Synteny-based Gene structure Annotation Polisher), which uses gene synteny information to accomplish precise and automated polishing of gene structure annotation of genomes. SynGAP offers exceptional capabilities in the improvement of gene structure annotation quality and the profiling of integrative gene synteny between species. Furthermore, an expression variation index is designed for comparative transcriptomics analysis to explore candidate genes responsible for the development of distinct traits observed in phylogenetically related species.