tbuckley/cabot-search huggingface dataset:
Assessment of the Tolerability and Effectiveness of Berotralstat for Long-term Prophylaxis in Hereditary Angioedema: Berolife Study Interim Analysis
Authors: Laurence Bouillet, Delphine Gobert, Isabelle Boccon-gibod, David Launay, Mona Villedieu, Jean-Charles Crave, Douglas Johnston, Olivier Fain
Journal: Journal of Allergy and Clinical Immunology (2024)
Glutamyl-prolyl-tRNA synthetase (EPRS1) drives tubulointerstitial nephritis-induced fibrosis by enhancing T cell proliferation and activity
Authors: Chaelin Kang, Donghwan Yun, Haein Yoon, Minki Hong, Juhyeon Hwang, Hyun Mu Shin, Seokwoo Park, Seongmin Cheon, Dohyun Han, Kyung Chul Moon, Hye Young Kim, Eun Young Choi, Eun-Young Lee, Myung Hee Kim, Chang Wook Jeong, Cheol Kwak, Dong Ki Kim, Kook-Hwan Oh, Kwon Wook Joo, Dong-Sup Lee, Yon Su Kim, Seung Seok Han
Journal: Kidney International (2024)
Impact Of Food Allergy On Work Productivity And Healthcare Resource Use In Patients With Allergic Asthma Treated With Omalizumab
Authors: Panida Sriaroon, Ignacio Ansotegui, Alessandro Fiocchi, R. Sharon Chinthrajah, S. Shahzad Mustafa, Sachin Gupta, My Hanh Zacharia, Briana Cameron, Pranil Raut, David Fleischer
Journal: Journal of Allergy and Clinical Immunology (2024)
Lebrikizumab Maintains Improvements in the Patient-Oriented Eczema Measure Through 2 Years of Treatment in Patients With Moderate-to-Severe Atopic Dermatitis
Authors: David Rosmarin, Andreas Wollenberg, Mark Boguniewicz, Carolyn Jack, Sebastien Barbarot, Vivian Shi, Marjolein de Bruin-Weller, Louise DeLuca-Carter, Evangeline Pierce, Chaoran Hu, Chunyuan Liu, Heidi Crane, Laia Bardolet, Martin Steinhoff
Journal: Journal of Allergy and Clinical Immunology (2024)
Outcomes of T Cell Receptor Excision Circle (TREC) Based Severe Combined Immunodeficiency (SCID) Newborn Screening (NBS) in Michigan: 10 Year Data
Authors: Devika Pillay, Aishwarya Navalpakam, Rebecca Shaulis, Mary Rhuehle, Isabel Hurden, Jenny Huang, Pavadee Poowuttikul
Journal: Journal of Allergy and Clinical Immunology (2024)
Patient and Caregiver Satisfaction and Quality of Life during Peanut Oral Immunotherapy at a Pediatric Academic Food Allergy Center
Authors: Chelsea Leef, Codi Horton, Heather Porter, Idil Ezhuthachan, Tricia Lee, Gerald Lee, Melinda Rathkopf, Brian Vickery
Journal: Journal of Allergy and Clinical Immunology (2024)
Historic methicillin-resistant Staphylococcus aureus: expanding current knowledge using molecular epidemiological characterization of a Swiss legacy collection
Authors: Vanni Benvenga, Aline Cuénod, Srinithi Purushothaman, Gottfried Dasen, Maja Weisser, Stefano Bassetti, Tim Roloff, Martin Siegemund, Ulrich Heininger, Julia Bielicki, Marianne Wehrli, Paul Friderich, Reno Frei, Andreas Widmer, Kathrin Herzog, Hans Fankhauser, Oliver Nolte, Thomas Bodmer, Martin Risch, Olivier Dubuis, Sigrid Pranghofer, Romana Calligaris-Maibach, Susanne Graf, Vincent Perreten, Helena M. B Seth-Smith, Adrian Egli
Journal: Genome Medicine (2024)

Few methicillin-resistant Staphylococcus aureus (MRSA) from the early years of its global emergence have been sequenced. Knowledge about evolutionary factors promoting the success of specific MRSA multi-locus sequence types (MLSTs) remains scarce. We aimed to characterize a legacy MRSA collection isolated from 1965 to 1987 and compare it against publicly available international and local genomes.
Pro-inflammatory feedback loops define immune responses to pathogenic Lentivirus infection
Authors: Aaron J. Wilk, Joshua O. Marceau, Samuel W. Kazer, Ira Fleming, Vincent N. Miao, Jennyfer Galvez-Reyes, Jason T. Kimata, Alex K. Shalek, Susan Holmes, Julie Overbaugh, Catherine A. Blish
Journal: Genome Medicine (2024)

Abstract Background The Lentivirus human immunodeficiency virus (HIV) causes chronic inflammation and AIDS in humans, with variable rates of disease progression between individuals driven by both host and viral factors. Similarly, simian lentiviruses vary in their pathogenicity based on characteristics of both the host species and the virus strain, yet the immune underpinnings that drive differential Lentivirus pathogenicity remain incompletely understood. Methods We profile immune responses in a unique model of differential lentiviral pathogenicity where pig-tailed macaques are infected with highly genetically similar variants of SIV that differ in virulence. We apply longitudinal single-cell transcriptomics to this cohort, along with single-cell resolution cell-cell communication techniques, to understand the immune mechanisms underlying lentiviral pathogenicity. Results Compared to a minimally pathogenic lentiviral variant, infection with a highly pathogenic variant results in a more delayed, broad, and sustained activation of inflammatory pathways, including an extensive global interferon signature. Conversely, individual cells infected with highly pathogenic Lentivirus upregulated fewer interferon-stimulated genes at a lower magnitude, indicating that highly pathogenic Lentivirus has evolved to partially escape from interferon responses. Further, we identify CXCL10 and CXCL16 as important molecular drivers of inflammatory pathways specifically in response to highly pathogenic Lentivirus infection. Immune responses to highly pathogenic Lentivirus infection are characterized by amplifying regulatory circuits of pro-inflammatory cytokines with dense longitudinal connectivity. Conclusions Our work presents a model of lentiviral pathogenicity where failures in early viral control mechanisms lead to delayed, sustained, and amplifying pro-inflammatory circuits, which in turn drives disease progression.
AEP promotes aberrant RNA splicing through DDX3X cleavage in solid tumors
Authors: Yadong Xie, Haohao Zhang, Xinyang Song
Journal: Journal of Clinical Investigation (2024)

Aberrant alternative splicing (AS) events have been identified in a variety of cancers. Although somatic mutations of splicing factors and dysregulation of RNA-binding proteins (RBPs) have been linked to AS and tumor malignancy, it remains unclear how upstream mechanisms contribute to cancer development via alternative gene splicing. In this issue of the JCI, Wenrui Zhang and colleagues identified the role of asparagine endopeptidase (AEP), an intracellular cysteine endopeptidase, in promoting solid tumor–associated RNA splicing. The authors demonstrated that tumor environmental factors such as oxygen and nutrient deprivation induce the activity of AEP in a HIF1A-dependent manner. The activated AEP, in turn, cleaves an RNA helicase DDX3X to promote its nuclear retention. The authors further showed that this DDX3X nuclear fraction engages with splicing machinery to induce AS events in several cancer cells. These findings suggest that targeting an AEP-dependent aberrant RNA splicing cascade may facilitate therapeutics for solid tumors.
Alcohol-associated liver disease
Authors: Bryan Mackowiak, Yaojie Fu, Luca Maccioni, Bin Gao
Journal: Journal of Clinical Investigation (2024)

Alcohol-associated liver disease (ALD) is a major cause of chronic liver disease worldwide, and comprises a spectrum of several different disorders, including simple steatosis, steatohepatitis, cirrhosis, and superimposed hepatocellular carcinoma. Although tremendous progress has been made in the field of ALD over the last 20 years, the pathogenesis of ALD remains obscure, and there are currently no FDA-approved drugs for the treatment of ALD. In this Review, we discuss new insights into the pathogenesis and therapeutic targets of ALD, utilizing the study of multiomics and other cutting-edge approaches. The potential translation of these studies into clinical practice and therapy is deliberated. We also discuss preclinical models of ALD, interplay of ALD and metabolic dysfunction, alcohol-associated liver cancer, the heterogeneity of ALD, and some potential translational research prospects for ALD.
Overcoming Clinical Resistance to EZH2 Inhibition Using Rational Epigenetic Combination Therapy
Authors: Yaniv Kazansky, Daniel Cameron, Helen S. Mueller, Phillip Demarest, Nadia Zaffaroni, Noemi Arrighetti, Valentina Zuco, Yasumichi Kuwahara, Romel Somwar, Marc Ladanyi, Rui Qu, Elisa de Stanchina, Filemon S. Dela Cruz, Andrew L. Kung, Mrinal M. Gounder, Alex Kentsis
Journal: Cancer Discovery (2024)

Epigenetic dependencies have become evident in many cancers. On the basis of antagonism between BAF/SWI-SNF and PRC2 in SMARCB1-deficient sarcomas, we recently completed the clinical trial of the EZH2 inhibitor tazemetostat. However, the principles of tumor response to epigenetic therapy in general, and tazemetostat in particular, remain unknown. Using functional genomics and diverse experimental models, we define molecular mechanisms of tazemetostat resistance in SMARCB1-deficient tumors. We found distinct acquired mutations that converge on the RB1/E2F axis and decouple EZH2-dependent differentiation and cell-cycle control. This allows tumor cells to escape tazemetostat-induced G1 arrest, suggests a general mechanism for effective therapy, and provides prospective biomarkers for therapy stratification, including PRICKLE1. On the basis of this, we develop a combination strategy to circumvent tazemetostat resistance using bypass targeting of AURKB. This offers a paradigm for rational epigenetic combination therapy suitable for translation to clinical trials for epithelioid sarcomas, rhabdoid tumors, and other epigenetically dysregulated cancers.
KIBRA repairs synaptic plasticity and promotes resilience to tauopathy-related memory loss
Authors: Grant Kauwe, Kristeen A. Pareja-Navarro, Lei Yao, Jackson H. Chen, Ivy Wong, Rowan Saloner, Helen Cifuentes, Alissa L. Nana, Samah Shah, Yaqiao Li, David Le, Salvatore Spina, Lea T. Grinberg, William W. Seeley, Joel H. Kramer, Todd C. Sacktor, Birgit Schilling, Li Gan, Kaitlin B. Casaletto, Tara E. Tracy
Journal: Journal of Clinical Investigation (2024)

Synaptic plasticity is obstructed by pathogenic tau in the brain, representing a key mechanism that underlies memory loss in Alzheimer's disease (AD) and related tauopathies. Here, we found that reduced levels of the memory-associated protein KIdney/BRAin (KIBRA) in the brain and increased KIBRA protein levels in cerebrospinal fluid are associated with cognitive impairment and pathological tau levels in disease. We next defined a mechanism for plasticity repair in vulnerable neurons using the C-terminus of the KIBRA protein (CT-KIBRA). We showed that CT-KIBRA restored plasticity and memory in transgenic mice expressing pathogenic human tau; however, CT-KIBRA did not alter tau levels or prevent tau-induced synapse loss. Instead, we found that CT-KIBRA stabilized the protein kinase Mζ (PKMζ) to maintain synaptic plasticity and memory despite tau-mediated pathogenesis. Thus, our results distinguished KIBRA both as a biomarker of synapse dysfunction and as the foundation for a synapse repair mechanism to reverse cognitive impairment in tauopathy.
Biofilm-derived oxylipin 10-HOME mediated immune response in women with breast implants
Authors: Tyler M. Bauer, Katherine A. Gallagher
Journal: Journal of Clinical Investigation (2024)

Breast implant illness (BII) is a poorly understood disease in which patients develop symptoms typical of autoimmune conditions following breast implantation. There is no known underlying cause, and patients often resort to breast implant removal and capsulectomy to alleviate symptoms. In this issue of the JCI, Khan and colleagues examined 86 breast explants from patients that reported BII symptoms and 55 control explants. The BII group showed a disproportionally high degree of biofilm, which was associated with oxylipin (10-HOME) on the implant surfaces. Injections of 10-HOME in the mammary fat pad of a murine model recapitulated BII symptoms and increased Th1 cell populations. Notably, macrophages in the periprosthetic tissue from BII patients were more likely to exhibit a proinflammatory phenotype, and naive T cells exposed to 10-HOME caused naive macrophages to differentiate to a proinflammatory phenotype. This work provides a pathophysiologic mechanism for a currently understudied and poorly characterized disease.
Harnessing Brain Pathology for Dementia Prevention
Authors: Yue Leng, Kristine Yaffe
Journal: JAMA Neurology (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 Neurology 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 Neurology journal
Healthy Lifestyle and Cognition in Older Adults With Common Neuropathologies of Dementia
Authors: Klodian Dhana, Puja Agarwal, Bryan D. James, Sue E. Leurgans, Kumar B. Rajan, Neelum T. Aggarwal, Lisa L. Barnes, David A. Bennett, Julie A. Schneider
Journal: JAMA Neurology (2024)

A healthy lifestyle is associated with better cognitive functioning in older adults, but whether this association is independent of the accumulation of dementia-related pathologies in the brain is uncertain.
Promising Safety Profile of Noninsulin Medications for Type 2 Diabetes in Early Pregnancy
Authors: Neda Ghaffari
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
Considerations in Early Autism Diagnosis
Authors: Nicola Cirillo
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
Transforming Value-Based Dementia Care—Implications for the GUIDE Model
Authors: Tarun Ramesh, Kushal Kadakia, Lidia Moura
Journal: JAMA Internal Medicine (2024)

This Viewpoint reviews the Guiding an Improved Dementia Experience (GUIDE) Model to assess its suitability in providing equitable and cost-effective dementia care and to compare it with previously introduced specialty care payment models to identify opportunities for refining payment innovation in dementia care.
Survey of Neonatal Management After Amnioinfusion for Anhydramnios
Authors: Ellen M. Bendel-Stenzel, Amaris M. Keiser, Kristin J. McKenna, Valerie Y. Chock, Suzanne Lopez, Jena L. Miller, Meredith A. Atkinson
Journal: JAMA Pediatrics (2024)

This survey study reports on use of renal replacement therapy, hemodynamic support, sedation, neuroimaging, and extracorporeal membrane oxygenation at Renal Anhydramnios Fetal Therapy trial sites for neonates with either bilateral renal agenesis or fetal kidney failure.
Officer-Involved Killings of Unarmed Black People and Racial Disparities in Sleep Health
Authors: Atheendar S. Venkataramani, Elizabeth F. Bair, Jacob Bor, Chandra L. Jackson, Ichiro Kawachi, Jooyoung Lee, Andrew Papachristos, Alexander C. Tsai
Journal: JAMA Internal Medicine (2024)

Racial disparities in sleep health may mediate the broader health outcomes of structural racism.
Preclinical Rodent Models for Human Bone Disease, Including a Focus on Cortical Bone
Authors: Natalie Y Y Koh, Justyna J Miszkiewicz, Mary Louise Fac, Natalie K Y Wee, Natalie A Sims
Journal: Endocrine Reviews (2024)

Preclinical models (typically ovariectomized rats and genetically altered mice) have underpinned much of what we know about skeletal biology. They have been pivotal for developing therapies for osteoporosis and monogenic skeletal conditions, including osteogenesis imperfecta, achondroplasia, hypophosphatasia, and craniodysplasias. Further therapeutic advances, particularly to improve cortical strength, require improved understanding and more rigorous use and reporting. We describe here how trabecular and cortical bone structure develop, are maintained, and degenerate with aging in mice, rats, and humans, and how cortical bone structure is changed in some preclinical models of endocrine conditions (eg, postmenopausal osteoporosis, chronic kidney disease, hyperparathyroidism, diabetes). We provide examples of preclinical models used to identify and test current therapies for osteoporosis, and discuss common concerns raised when comparing rodent preclinical models to the human skeleton. We focus especially on cortical bone, because it differs between small and larger mammals in its organizational structure. We discuss mechanisms common to mouse and human controlling cortical bone strength and structure, including recent examples revealing genetic contributors to cortical porosity and osteocyte network configurations during growth, maturity, and aging. We conclude with guidelines for clear reporting on mouse models with a goal for better consistency in the use and interpretation of these models.
Music as an Intervention to Improve the Hemodynamic Response of Ketamine in Depression
Authors: Kyle T. Greenway, Nicolas Garel, Lê-Anh L. Dinh-Williams, Serge Beaulieu, Gustavo Turecki, Soham Rej, Stephane Richard-Devantoy
Journal: JAMA Network Open (2024)

This randomized clinical trial explores whether music improves the hemodynamic response of ketamine among patients with treatment-resistant depression in Canada.
Three-Item Dimensions of Anger Reactions Scale
Authors: David Forbes, Cynthia A. LeardMann, Ellie Lawrence-Wood, Javier Villalobos, Kelsey Madden, Ian A. Gutierrez, Sean Cowlishaw, Jenelle Baur, Amy B. Adler
Journal: JAMA Network Open (2024)

Importance Problematic anger is prevalent and associated with adjustment difficulties in military populations. To facilitate measurement of problematic anger, a very brief valid measure is needed. Objective To reduce the Dimensions of Anger Reactions 5-item (DAR-5) scale to a very brief measure. Design, Setting, and Participants This cross-sectional study used survey data collected between 2014 and 2016 in the Australian Transition and Well-Being Research Programme and US Millennium Cohort Study. Participants were service members who were actively serving or had transitioned out of the military (separated). Statistical analyses were performed from September 2021 to June 2023. Main Outcomes and Measures The DAR-5 was reduced to the 3 experiential items: frequency, intensity, and duration (the DAR-3). Psychometrics for the DAR-3 and DAR-5 were compared in terms of standardized Cronbach α, positive screening result, mean, and SD. Analyses were stratified by Australian and US military service status cohorts (active duty and separated). Results A total of 71 010 participants were included from Australia and the US. Of 10 900 Australian participants (8145 active duty participants [74.7%]; 2755 separated participants [25.3%]), 5893 (55.2%) were aged 40 years or older and 8774 (80.5%) were male; of 60 110 US participants (24 706 active duty participants [41.1%]; 35 404 separated participants [58.9%]), 28 804 (47.9%) were aged 30 to 39 years and 43 475 (72.3%) were male. The DAR-3 demonstrated good internal consistency in the active duty (Australia: mean [SD] score, 4.97 [2.5]; α = 0.90; US: mean [SD] score, 5.04 [2.6]; α = 0.87) and separated (Australia: mean [SD] score, 6.53 [3.4]; α = 0.92; US: mean [SD] score, 6.05 [3.2]; α = 0.91) samples. The cutoff score of 8 or greater on the DAR-3 had optimal sensitivity and specificity across all samples. DAR-3 and DAR-5 were associated with posttraumatic stress disorder (PTSD), depression, aggression, and relationship conflict. While the scales did not significantly differ in their associations with PTSD, depression, and relationship conflict, the magnitude of association for aggression was significantly lower in US samples using the DAR-3 (eg, US active duty sample: DAR-5 OR, 9.96; 95% CI, 9.01-11.00; DAR-3 OR, 8.36; 95% CI, 7.58-9.22). Conclusions and Relevance In this cross-sectional study of a very brief measure of anger, each item contributed to the overall strength of the measure without losing psychometric strength compared with the DAR-5. The consistency of these findings across military and veteran samples in Australian and US populations demonstrated the psychometric robustness of the DAR-3.
Considerations in Early Autism Diagnosis
Authors: Nihit Gupta, Mayank Gupta
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