tbuckley/cabot-search huggingface dataset:
Exposure to Polybrominated Diphenyl Ethers and Risk of All-Cause and Cause-Specific Mortality
Authors: Buyun Liu, Hans-Joachim Lehmler, Ziyi Ye, Xing Yuan, Yuxiang Yan, Yuntian Ruan, Yi Wang, Yu Yang, Shuhan Chen, Wei Bao
Journal: JAMA Network Open (2024)

Importance Polybrominated diphenyl ethers (PBDEs) are an important group of persistent organic pollutants with endocrine-disrupting properties. However, prospective cohort studies regarding the association of PBDE exposure with long-term health outcomes, particularly mortality, are lacking. Objective To examine the association of environmental exposure to PBDEs with risk of all-cause and cause-specific mortality. Design, Setting, and Participants This nationally representative cohort study used data from the National Health and Nutrition Examination Survey 2003 to 2004 and linked mortality information through December 31, 2019. Adults aged 20 years or older with available data on PBDE measurements and mortality were included. Statistical analysis was performed from February 2022 to April 2023. Exposures PBDE analytes in serum samples were measured using solid phase extraction and isotope dilution gas chromatography high-resolution mass spectrometry. Main Outcomes and Measures All-cause mortality, cancer mortality, and cardiovascular mortality. Results This study included 1100 participants (mean [SE] age, 42.9 [0.6] years; proportion [SE] female, 51.8% [1.6%]; proportion [SE] Hispanic, 12.9% [2.7%]; proportion [SE] non-Hispanic Black, 10.5% [1.6%]; proportion [SE] non-Hispanic White, 70.8% [3.7%]; proportion [SE] other race and ethnicity, 5.8% [1.1%]). During 16 162 person-years of follow-up (median [IQR] follow-up, 15.8 [15.2-16.3] years; maximum follow-up, 17 years), 199 deaths occurred. Participants with higher serum PBDE levels were at higher risk for death. After adjustment for age, sex, and race and ethnicity, lifestyle and socioeconomic factors, and body mass index, participants with the highest tertile of serum PBDE levels had an approximately 300% increased risk of cancer mortality (HR, 4.09 [95% CI, 1.71-9.79]) compared with those with the lowest tertile of serum PBDE levels. No significant association of PBDE exposure with all-cause mortality (HR, 1.43 [95% CI, 0.98-2.07]) or cardiovascular mortality (HR, 0.92 [95% CI, 0.41-2.08]) was observed. Conclusions and Relevance In this nationally representative cohort study, PBDE exposure was significantly associated with an increased risk of cancer mortality. Further studies are needed to replicate the findings and determine the underlying mechanisms.
Sleep apnea and ischemic stroke— a perspective for translational preclinical modelling
Authors: I.J. Biose, A.B. Bakare, H. Wang, T.E. Gressett, G.J. Bix
Journal: Sleep Medicine Reviews (2024)

Obstructive sleep apnea (OSA) is associated with ischemic stroke. There is, however, a lack of knowledge on the exact cause-effect relationship, and preclinical models of OSA for experimental ischemic stroke investigations are not well characterized. In this review, we discuss sleep apnea and its relationship with stroke risk factors. We consider how OSA may lead to ischemic stroke and how OSA-induced metabolic syndrome and hypothalamic-pituitary axis dysfunction could serve as therapeutic targets to prevent ischemic stroke. Further, we examine the translational potential of established preclinical models of OSA. We conclude that metabolic syndrome and aging, which are often overlooked in the context of experimental stroke and OSA studies, are crucial for experimental consideration to improve the body of knowledge as well as the translational potential of investigative efforts.
Trans-eQTL mapping in gene sets identifies network effects of genetic variants
Authors: Lili Wang, Nikita Babushkin, Zhonghua Liu, Xuanyao Liu
Journal: Cell Genomics (2024)

Nearly all trait-associated variants identified in genome-wide association studies (GWASs) are noncoding. The cis regulatory effects of these variants have been extensively characterized, but how they affect gene regulation in trans has been the subject of fewer studies because of the difficulty in detecting trans-expression quantitative loci (eQTLs). We developed trans-PCO for detecting trans effects of genetic variants on gene networks. Our simulations demonstrate that trans-PCO substantially outperforms existing trans-eQTL mapping methods. We applied trans-PCO to two gene expression datasets from whole blood, DGN (N = 913) and eQTLGen (N = 31,684), and identified 14,985 high-quality trans-eSNP-module pairs associated with 197 co-expression gene modules and biological processes. We performed colocalization analyses between GWAS loci of 46 complex traits and the trans-eQTLs. We demonstrated that the identified trans effects can help us understand how trait-associated variants affect gene regulatory networks and biological pathways.
Futile cycles: Emerging utility from apparent futility
Authors: Anand Kumar Sharma, Radhika Khandelwal, Christian Wolfrum
Journal: Cell Metabolism (2024)

Futile cycles are biological phenomena where two opposing biochemical reactions run simultaneously, resulting in a net energy loss without appreciable productivity. Such a state was presumed to be a biological aberration and thus deemed an energy-wasting "futile" cycle. However, multiple pieces of evidence suggest that biological utilities emerge from futile cycles. A few established functions of futile cycles are to control metabolic sensitivity, modulate energy homeostasis, and drive adaptive thermogenesis. Yet, the physiological regulation, implication, and pathological relevance of most futile cycles remain poorly studied. In this review, we highlight the abundance and versatility of futile cycles and propose a classification scheme. We further discuss the energetic implications of various futile cycles and their impact on basal metabolic rate, their bona fide and tentative pathophysiological implications, and putative drug interactions.
Advancing Evidence-Based Peripheral Intravenous Catheter Securement
Authors: Amanda Bettencourt, Halley Ruppel, Christopher P. Bonafide
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
Multitarget Stool RNA Testing—Reply
Authors: Erica K. Barnell, David A. Lieberman
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 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
Clinical Reasoning of a Generative Artificial Intelligence Model Compared With Physicians
Authors: Stephanie Cabral, Daniel Restrepo, Zahir Kanjee, Philip Wilson, Byron Crowe, Raja-Elie Abdulnour, Adam Rodman
Journal: JAMA Internal Medicine (2024)

This cross-sectional study assesses the ability of a large language model to process medical data and display clinical reasoning compared with the ability of attending physicians and residents.
Controlling Multidrug-Resistant Organisms Across Patient-Sharing Networks
Authors: Christopher J. Crnich
Journal: JAMA (2024)

Gabrielle M. Gussin, MS; James A. McKinnell, MD; Raveena D. Singh, MA; Loren G. Miller, MD, MPH; Ken Kleinman, ScD; Raheeb Saavedra, AS; Thomas Tjoa, MPH, MS; Shruti K. Gohil, MD, MPH; Tabitha D. Catuna, MPH; Lauren T. Heim, MPH; Justin Chang, MD; Marlene Estevez, BA; Jiayi He, MS; Kathleen O'Donnell, MPH; Matthew Zahn, MD; Eunjung Lee, MD, PhD; Chase Berman, BS; Jenny Nguyen, BA; Shalini Agrawal, BS; Isabel Ashbaugh, MSc; Christine Nedelcu, BS; Philip A. Robinson, MD; Steven Tam, MD; Steven Park, MD, PhD; Kaye D. Evans, BA, MT; Julie A. Shimabukuro, BS; Bruce Y. Lee, MD, MBA; Emily Fonda, MD, MMM; John A. Jernigan, MD, MS; Rachel B. Slayton, PhD, MPH; Nimalie D. Stone, MD, MS; Lynn Janssen, MS; Robert A. Weinstein, MD; Mary K. Hayden, MD; Michael Y. Lin, MD, MPH; Ellena M. Peterson, PhD; Cassiana E. Bittencourt, MD; Susan S. Huang, MD, MPH; CDC Safety and Healthcare Epidemiology Prevention Research Development (SHEPheRD) Program
Nuclear KRT19 is a transcriptional corepressor promoting histone deacetylation and liver tumorigenesis
Authors: Shixun Han, Haonan Fan, Guoxuan Zhong, Lei Ni, Wenhao Shi, Yushan Fang, Chenliang Wang, Li Wang, Lang Song, Jianhui Zhao, Mei Tang, Bing Yang, Li Li, Xueli Bai, Qi Zhang, Tingbo Liang, Yanhui Xu, Xin-Hua Feng, Chen Ding, Dong Fang, Bin Zhao
Journal: Hepatology (2024)

Background and Aims: Epigenetic reprogramming and escape from terminal differentiation are poorly understood enabling characteristics of liver cancer. Keratin 19 (KRT19), classically known to form the intermediate filament cytoskeleton, is a marker of stemness and worse prognosis in liver cancer. This study aimed to address the functional roles of KRT19 in liver tumorigenesis and to elucidate the underlying mechanisms. Approach and Results: Using multiplexed genome editing of hepatocytes in vivo, we demonstrated that KRT19 promoted liver tumorigenesis in mice. Cell fractionation revealed a previously unrecognized nuclear fraction of KRT19. Tandem affinity purification identified histone deacetylase 1 and REST corepressor 1, components of the corepressor of RE-1 silencing transcription factor (CoREST) complex as KRT19-interacting proteins. KRT19 knockout markedly enhanced histone acetylation levels. Mechanistically, KRT19 promotes CoREST complex formation by enhancing histone deacetylase 1 and REST corepressor 1 interaction, thus increasing the deacetylase activity. ChIP-seq revealed hepatocyte-specific genes, such as hepatocyte nuclear factor 4 alpha ( HNF4A ), as direct targets of KRT19-CoREST. In addition, we identified forkhead box P4 as a direct activator of aberrant KRT19 expression in liver cancer. Furthermore, treatment of primary liver tumors and patient-derived xenografts in mice suggest that KRT19 expression has the potential to predict response to histone deacetylase 1 inhibitors especially in combination with lenvatinib. Conclusions: Our data show that nuclear KRT19 acts as a transcriptional corepressor through promoting the deacetylase activity of the CoREST complex, resulting in dedifferentiation of liver cancer. These findings reveal a previously unrecognized function of KRT19 in directly shaping the epigenetic landscape in cancer.
Helper T cell immunity in humans with inherited CD4 deficiency
Authors: Antoine Guérin, Marcela Moncada-Vélez, Katherine Jackson, Masato Ogishi, Jérémie Rosain, Mathieu Mancini, David Langlais, Andrea Nunez, Samantha Webster, Jesse Goyette, Taushif Khan, Nico Marr, Danielle T. Avery, Geetha Rao, Tim Waterboer, Birgitta Michels, Esmeralda Neves, Cátia Iracema Morais, Jonathan London, Stéphanie Mestrallet, Pierre Quartier dit Maire, Bénédicte Neven, Franck Rapaport, Yoann Seeleuthner, Atar Lev, Amos J. Simon, Jorge Montoya, Ortal Barel, Julio Gómez-Rodríguez, Julio C. Orrego, Anne-Sophie L’Honneur, Camille Soudée, Jessica Rojas, Alejandra C. Velez, Irini Sereti, Benjamin Terrier, Nancy Marin, Luis F. García, Laurent Abel, Stéphanie Boisson-Dupuis, Joel Reis, Antonio Marinho, Andrea Lisco, Emilia Faria, Christopher C. Goodnow, Julia Vasconcelos, Vivien Béziat, Cindy S. Ma, Raz Somech, Jean-Laurent Casanova, Jacinta Bustamante, Jose Luis Franco, Stuart G. Tangye
Journal: The Journal of Experimental Medicine (2024)

CD4+ T cells are vital for host defense and immune regulation. However, the fundamental role of CD4 itself remains enigmatic. We report seven patients aged 5–61 years from five families of four ancestries with autosomal recessive CD4 deficiency and a range of infections, including recalcitrant warts and Whipple’s disease. All patients are homozygous for rare deleterious CD4 variants impacting expression of the canonical CD4 isoform. A shorter expressed isoform that interacts with LCK, but not HLA class II, is affected by only one variant. All patients lack CD4+ T cells and have increased numbers of TCRαβ+CD4−CD8− T cells, which phenotypically and transcriptionally resemble conventional Th cells. Finally, patient CD4−CD8− αβ T cells exhibit intact responses to HLA class II–restricted antigens and promote B cell differentiation in vitro. Thus, compensatory development of Th cells enables patients with inherited CD4 deficiency to acquire effective cellular and humoral immunity against an unexpectedly large range of pathogens. Nevertheless, CD4 is indispensable for protective immunity against at least human papillomaviruses and Trophyrema whipplei.
An algorithm for the diagnosis, pathogenesis and treatment of chronic spontaneous urticaria, 2024 update
Authors: Allen P. Kaplan, Marta Ferrer
Journal: Allergy (2024)

Marta Ferrer has received honoraria (advisory board, speaker) from Novartis, Menarini, Uriach, FAES, Pfizer and MSD and has received a research Grant from GSK and Novartis. Data sharing is not applicable to this article as no new data were created or analyzed in this study.
Impact of baseline kidney dysfunction on oral diuretic efficacy following hospitalization for heart failure – insights from <scp>TRANSFORM‐HF</scp>
Authors: Pieter Martens, Stephen J. Greene, Robert J. Mentz, Shuang Li, Daniel Wojdyla, Chris J. Kapelios, Wilfried Mullens, Michael E. Hall, Fassil Ketema, Dong‐Yun Kim, Eric L. Eisenstein, Kevin Anstrom, James C. Fang, Bertram Pitt, Eric J. Velazquez, W.H. Wilson Tang
Journal: European Journal of Heart Failure (2024)
Circulating tumor plasma cells and peripheral blood measurable residual disease assessment in multiple myeloma patients not planned for upfront transplant
Authors: Prashant R. Tembhare, Harshini Sriram, Twinkle Khanka, Sanghamitra Gawai, Bhausaheb Bagal, Sitaram G. Ghogale, Nilesh Deshpande, Karishma Girase, Jagruti Patil, Syed Khaizer Hasan, Dhanalaxmi Shetty, Kinjalka Ghosh, Gaurav Chatterjee, Sweta Rajpal, Nikhil V. Patkar, Hasmukh Jain, Sachin Punatar, Anant Gokarn, Lingaraj Nayak, Sumeet Mirgh, Nishant Jindal, Manju Sengar, Navin Khattry, Papagudi G. Subramanian, Sumeet Gujral
Journal: HemaSphere (2024)

Abstract Circulating tumor plasma cells (CTPCs) provide a noninvasive alternative for measuring tumor burden in newly diagnosed multiple myeloma (NDMM). Moreover, measurable residual disease (MRD) assessment in peripheral blood (PBMRD) can provide an ideal alternative to bone marrow MRD, which is limited by its painful nature and technical challenges. However, the clinical significance of PBMRD in NDMM still remains uncertain. Additionally, data on CTPC in NDMM patients not treated with transplant are scarce. We prospectively studied CTPC and PBMRD in 141 NDMM patients using highly sensitive multicolor flow cytometry (HS‐MFC). PBMRD was monitored at the end of three cycles (PBMRD1) and six cycles (PBMRD2) of chemotherapy in patients with detectable baseline CTPC. Patients received bortezomib‐based triplet therapy and were not planned for an upfront transplant. Among baseline risk factors, CTPC ≥ 0.01% was independently associated with poor progression‐free survival (PFS) (hazard ratio [HR] = 2.77; p = 0.0047) and overall survival (OS) (HR = 2.9; p = 0.023) on multivariate analysis. In patients with detectable baseline CTPC, undetectable PBMRD at both subsequent time points was associated with longer PFS (HR = 0.46; p = 0.0037), whereas detectable PBMRD at any time point was associated with short OS (HR = 3.25; p = 0.004). Undetectable combined PBMRD (PBMRD1 and PBMRD2) outperformed the serum‐immunofixation‐based response. On multivariate analysis, detectable PBMRD at any time point was independently associated with poor PFS (HR = 2.0; p = 0.025) and OS (HR = 3.97; p = 0.013). Thus, our findings showed that CTPC and PBMRD assessment using HS‐MFC provides a robust, noninvasive biomarker for NDMM patients not planned for an upfront transplant. Sequential PBMRD monitoring has great potential to improve the impact of the existing risk stratification and response assessment models.
Consensus recommendation for prenatal, neonatal and postnatal management of congenital cytomegalovirus infection from the European congenital infection initiative (ECCI)
Authors: Marianne Leruez-Ville, Christos Chatzakis, Daniele Lilleri, Daniel Blazquez-Gamero, Ana Alarcon, Nicolas Bourgon, Ina Foulon, Jacques Fourgeaud, Anna Gonce, Christine E. Jones, Paul Klapper, André Krom, Tiziana Lazzarotto, Hermione Lyall, Paulo Paixao, Vassiliki Papaevangelou, Elisabeth Puchhammer, George Sourvinos, Pamela Vallely, Yves Ville, Ann Vossen
Journal: The Lancet Regional Health - Europe (2024)

Congenital cytomegalovirus (cCMV) infection carries a significant burden with a 0.64% global prevalence and a 17–20% chance of serious long-term effects in children. Since the last guidelines, our understanding, particularly regarding primary maternal infections, has improved. A cCMV guidelines group was convened under the patronage of the European Society of Clinical Virology in April 2023 to refine these insights. The quality and validity of selected studies were assessed for potential biases and the GRADE framework was employed to evaluate quality of evidence across key domains. The resulting recommendations address managing cCMV, spanning prevention to postnatal care. Emphasizing early and accurate maternal diagnosis through serological tests enhances risk management and prevention strategies, including using valaciclovir to prevent vertical transmission. The guidelines also strive to refine personalized postnatal care based on risk assessments, ensuring targeted interventions for affected families.
Comparison of whole‐genome and immunoglobulin‐based circulating tumor DNA assays in diffuse large B‐cell lymphoma
Authors: Reid W. Merryman, Justin Rhoades, Kan Xiong, Robert A. Redd, Katherine Antel, Hyun Hwan An, Mikaela McDonough, Liliana Guerrero, Andela Crnjac, Sainetra Sridhar, Timothy Blewett, Ju Cheng, Parastoo B. Dahi, Yago Nieto, Robin M. Joyce, Yi‐Bin Chen, Alex F. Herrera, Philippe Armand, Mark Murakami, Viktor A. Adalsteinsson
Journal: HemaSphere (2024)
Mucus and Biofilm Penetrating Nanoplatform as an Ultrasound‐Induced Free Radical Initiator for Targeted Treatment of <i>Helicobacter pylori</i> Infection
Authors: Jinjie Fan, Yuze Dong, Yue Sun, Yalan Ji, Jie Feng, Peijuan Yan, Yingnan Zhu
Journal: Advanced Healthcare Materials (2024)

Abstract Helicobacter pylori ( H. pylori ) infection is closely associated with the development of various gastric diseases. The effectiveness of current clinical antibiotic therapy is hampered by the rise of drug‐resistant strains and the formation of H. pylori biofilm. This paper reports a sonodynamic nanocomposite PtCu 3 ‐PDA@AIPH@Fucoidan (PPAF), which consists of dopamine‐modified inorganic sonosensitizers PtCu 3 , alkyl radicals (R•) generator AIPH and fucoidan, can penetrate the mucus layer, target H. pylori , disrupt biofilms, and exhibit excellent bactericidal ability. In vitro experiments demonstrate that PPAF exhibits excellent acoustic kinetic properties, generating a significant amount of reactive oxygen species and oxygen‐independent R• for sterilization under ultrasound stimulation. Simultaneously, the produced N 2 can enhance the cavitation effect, aiding PPAF nanoparticles in penetrating the gastric mucus layer and disrupting biofilm integrity. This disruption allows more PPAF nanoparticles to bind to biofilm bacteria, facilitating the eradication of H. pylori . In vivo experiments demonstrate that ultrasound‐stimulated PPAF exhibited significant antibacterial efficacy against H. pylori . Moreover, it effectively modulated the expression levels of inflammatory factors and maintained gastrointestinal microbiota stability when compared to the antibiotic treatment group. In summary, PPAF nanoparticles present a potential alternative to antibiotics, offering an effective and healthy option for treating H. pylori infection.
LXRα Promotes Abdominal Aortic Aneurysm Formation Through UHRF1 Epigenetic Modification of miR-26b-3p
Authors: Xiao Guo, Jianmei Zhong, Yichao Zhao, Yanan Fu, Ling-yue Sun, Ancai Yuan, Junling Liu, Alex F. Chen, Jun Pu
Journal: Circulation (2024)

Abdominal aortic aneurysm (AAA) is a severe aortic disease without effective pharmacological approaches. The nuclear hormone receptor LXRα (liver X receptor α), encoded by the
BRCC3 Regulation of ALK2 in Vascular Smooth Muscle Cells: Implication in Pulmonary Hypertension
Authors: Hui Shen, Ya Gao, Dedong Ge, Meng Tan, Qing Yin, Tong-You Wade Wei, Fangzhou He, Tzong-Yi Lee, Zhongyan Li, Yuqin Chen, Qifeng Yang, Zhangyu Liu, Xinxin Li, Zixuan Chen, Yi Yang, Zhengang Zhang, Patricia A. Thistlethwaite, Jian Wang, Atul Malhotra, Jason X.-J. Yuan, John Y.-J. Shyy, Kaizheng Gong
Journal: Circulation (2024)

An imbalance of antiproliferative BMP (bone morphogenetic protein) signaling and proliferative TGF-β (transforming growth factor-β) signaling is implicated in the development of pulmonary arterial hypertension (PAH). The posttranslational modification (eg, phosphorylation and ubiquitination) of TGF-β family receptors, including BMPR2 (bone morphogenetic protein type 2 receptor)/ALK2 (activin receptor-like kinase-2) and TGF-βR2/R1, and receptor-regulated Smads significantly affects their activity and thus regulates the target cell fate. BRCC3 modifies the activity and stability of its substrate proteins through K63-dependent deubiquitination. By modulating the posttranslational modifications of the BMP/TGF-β-PPARγ pathway, BRCC3 may play a role in pulmonary vascular remodeling, hence the pathogenesis of PAH.