tbuckley/cabot-search huggingface dataset:
Safety and efficacy of tofacitinib for the treatment of patients with juvenile idiopathic arthritis: preliminary results of an open-label, long-term extension study
Authors: Hermine I Brunner, Jonathan D Akikusa, Eslam Al-Abadi, John F Bohnsack, Alina Lucica Boteanu, Gaelle Chedeville, Ruben Cuttica, Wendy De La Pena, Lawrence Jung, Ozgur Kasapcopur, Katarzyna Kobusinska, Grant S Schulert, Claudia Neiva, Rafael Rivas-Chacon, Juan Cruz Rizo Rodriguez, Monica Vazquez-Del Mercado, Linda Wagner-Weiner, Jennifer E Weiss, Carine Wouters, Holly Posner, Ann Wouters, Cheng Chang, Claire White, Keith Kanik, Shixue Liu, Alberto Martini, Daniel J Lovell, Nicolino Ruperto
Journal: Annals of the Rheumatic Diseases (2024)

We report the safety, tolerability and efficacy of tofacitinib in patients with juvenile idiopathic arthritis (JIA) in an ongoing long-term extension (LTE) study.
Concordance between clinician-reported and patient-reported outcomes of eyebrow and eyelash hair loss in patients with severe alopecia areata: Results from BRAVE-AA1 and BRAVE-AA2 studies
Authors: Arash Mostaghimi, Justin Ko, Antonella Tosti, Amy McMichael, Manabu Ohyama, Taisuke Ito, Yves Dutronc, Susan Ball, Guanglei Yu, Mwangi Murage, Yun-Fei Chen, Chiara Chiasserini, Andreas Wollenberg
Journal: Journal of the American Academy of Dermatology (2024)
P2Y2R and Cyst Growth in Polycystic Kidney Disease
Authors: Andre Kraus, Kathrin Skoczynski, Martin Brötsch, Nicolai Burzlaff, Jens Leipziger, Mario Schiffer, Maike Büttner-Herold, Bjoern Buchholz
Journal: Journal of the American Society of Nephrology (2024)

Key Points Polycystic kidney disease (PKD) is characterized by continuous cyst growth, which results in a decline in kidney function. Deletion of P2Y2R and pharmacological antagonism of purinergic signaling significantly reduced cyst growth in an orthologous PKD mouse model. P2Y2R was expressed in cysts of human PKD nephrectomies, which makes P2Y2R a reasonable target for treatment of PKD. Background Autosomal dominant polycystic kidney disease (ADPKD) is characterized by multiple bilateral kidney cysts that gradually enlarge, resulting in a decline in kidney function. Cyst growth is significantly driven by ATP-dependent chloride secretion mediated by the ion channel TMEM16A. This pathway is further augmented in advanced stages of the disease by hypoxia and activation of hypoxia-inducible factor (HIF)-1 α . The mechanisms by which ATP leads to activation of TMEM16A and how HIF-1 α contributes to cyst growth in vivo have remained elusive. Methods Mice with an inducible tubule-specific deletion of Pkd1 were compared with mice with an additional codeletion of the purinergic receptor P2y2r . Furthermore, animals were challenged by pharmacological activation of HIF-1 α and Pkd1 -deficient mice were treated with suramin, an antagonist of purinergic signaling. In addition, expression of P2Y2R, TMEM16A, and HIF-1 α was analyzed in nephrectomy samples from 27 patients with ADPKD. Results Genetic deletion of P2y2r significantly inhibited cyst growth in vivo . In addition, aggravation of the polycystic phenotype mediated by pharmacological activation of HIF-1 α was reduced by deletion of P2y2r . Application of suramin to pharmacologically inhibit purinergic signaling also suppressed cyst enlargement in vivo . Analysis of kidney samples from 27 patients with ADPKD revealed significant expression of P2Y2R at the luminal site of the cyst-lining epithelium. Conclusions P2Y2R was significantly expressed in human and mouse polycystic kidneys. Deletion and antagonism of P2Y2R reduced cyst enlargement in an ADPKD mouse model.
Bariatric Metabolic Surgery vs Glucagon-Like Peptide-1 Receptor Agonists and Mortality
Authors: Dror Dicker, Yael Wolff Sagy, Noga Ramot, Erez Battat, Philip Greenland, Ronen Arbel, Gil Lavie, Orna Reges
Journal: JAMA Network Open (2024)

Importance Evidence regarding the relative effectiveness of bariatric metabolic surgery (BMS) and glucagon-like peptide-1 receptor agonists (GLP-1RAs) in reducing mortality and major adverse cardiovascular events (MACEs) is limited. Objective To compare all-cause mortality and nonfatal MACEs associated with BMS vs GLP-1RAs for adults with obesity and diabetes and without known cardiovascular disease. Design, Setting, and Participants This observational, retrospective cohort study was based on data obtained from the electronic medical records of Clalit Health Services (Clalit), the largest health care organization in Israel. The study included 6070 members aged 24 years or older, who had diabetes and obesity and no prior history of ischemic heart disease, ischemic stroke, or congestive heart failure. Patients who underwent BMS and patients who received GLP-1RAs from January 1, 2008, through December 31, 2021, were matched 1:1 by age, sex, and clinical characteristics. Follow-up ended December 31, 2022. Exposures Initiation of BMS or GLP-1RAs. Main Outcomes and Measures The primary outcome was all-cause mortality, assessed by multivariate Cox proportional hazards regression models. The secondary outcome was nonfatal MACEs, assessed by multivariate competing risk models. Results The study included 3035 matched pairs of patients (total, 6070; mean [SD] age, 51.0 [9.5] years; 3938 women [64.9%]), who were followed up for a median of 6.8 years (IQR, 4.1-9.4 years). Among those with a diabetes duration of 10 years or less (2371 pairs), mortality was lower for those who underwent BMS than for those treated with GLP-1RAs (hazard ratio [HR], 0.38; 95% CI, 0.25-0.58). This association became nonsignificant when weight loss during the follow-up period was also included in the model (HR, 0.79; 95% CI, 0.43-1.48). Among patients with a duration of diabetes longer than 10 years (664 pairs), no survival advantage was demonstrated for BMS over GLP-1RA (HR, 0.65; 95% CI, 0.39-1.08). The risk for nonfatal MACEs did not differ between the treatment groups (HR, 0.74; 95% CI, 0.49-1.10 among patients with a diabetes duration of ≤10 years; HR, 1.21; 95% CI, 0.80-1.85 among patients with a diabetes duration of &amp;amp;gt;10 years). Conclusions and Relevance In this cohort study, BMS was associated with greater reduced mortality compared with first-generation GLP-1RAs among individuals with a diabetes duration of 10 years or less, mediated via greater weight loss. No differences in the risk for mortality were observed between the treatment modalities among individuals with a longer duration of diabetes, nor in the occurrence of nonfatal MACEs among all patients.
Receiving Abortion Medication Through Mail Was Safe, Effective
Authors: Emily Harris
Journal: JAMA (2024)

Daniel Grossman, MD; Sarah Raifman, MSc; Natalie Morris, MPH; Andrea Arena, MD; Lela Bachrach, MD; Jessica Beaman, MD; M. Antonia Biggs, PhD; Amy Collins, MD, MS; Curtiss Hannum, CRNP; Stephanie Ho, MD; Susan M. Seibold-Simpson, PhD, MPH, RN; Mindy Sobota, MD, MS, MPhil; Kristina Tocce, MD, MPH; Eleanor B. Schwarz, MD; Marji Gold, MD
Lung Ultrasonography Scores in Preterm Infants and Respiratory Outcomes at Age 2 Years
Authors: Luca Bonadies, Daniele De Luca, Maria Auciello, Laura Moschino, Sabrina Congedi, Daniel Nardo, Eugenio Baraldi
Journal: JAMA Network Open (2024)

This cohort study examines the role of lung ultrasonography score in estimating respiratory episodes needing drugs or hospitalization in premature infants.
Self-Monitoring and Managing Medications Improved High Blood Pressure
Authors: Emily Harris
Journal: JAMA (2024)

Patricia Martínez-Ibáñez, PhD; Irene Marco-Moreno, PhD; Aníbal García-Sempere, PhD; Salvador Peiró, PhD; Lucia Martínez-Ibáñez, MD; Ignacio Barreira-Franch, MD; Laura Bellot-Pujalte, MD; Eugenia Avelino-Hidalgo, MD; Marina Escrig-Veses, MD; María Bóveda-García, MD; Mercedes Calleja-del-Ser, MD; Celia Robles-Cabaniñas, BBioTech; Isabel Hurtado, PhD; Clara L. Rodríguez-Bernal, PhD; Margarita Giménez-Loreiro, MD; Gabriel Sanfélix-Gimeno, PhD; José Sanfélix-Genovés, PhD; ADAMPA Research Group; Joaquín Abad Carrasco; Maria Virginia Agudo Escagüés; Jorge Navarro-Perez; Rosa Maria Bartual Penella; Rosa Carrión Villanueva; Ana Costa Alcaraz; Isabel Cristófol López; Rosario González Candelas; Ricardo González Espadas; Luis González Luján; Victoria Gosalbes; Enrique Guinot Martínez; Emilio Luis López Torres; Silvia Molla LLosa; Víctor Moreno Comins; Miriam Moreno Prat; Mª José Puchades Company; Ángela Ramos García; Paloma Ramos Ruiz; Pilar Roca Navarro; Rosa Saiz Rodriguez; Julia Lorena Salanova Chilet; Ana Tchang Sanchez; Francisca Torres Asensi; Ruth Uribes Fillol; Cristina Valle García; Macarena Villar Ruiz; Marta Alcocer Escribano; Laura Almudever Campo; Lorena Cruz Bautista; Mª Begoña Fuertes Fernandez; Victor García Olivencia; Carmen Molla Orts; María José Muñoz Sanchíz; Francisca Osuna Sabariego; Emilia Ramón Carretero; Pilar Roca Roda; Esther Rodriguez García; Maria Rosa Serrada Iranzo; Eva Sierra García; Adina A Iftimi; Andreu Ferrero-Gregori
Validation of a Handheld 6-Lead Device for QT Interval Monitoring in Resource-Limited Settings
Authors: John Z. Metcalfe, Tamsin Economou, Fahd Naufal, Murat Kucukosmanoglu, Robert Kleiman, Patrick P. J. Phillips, Francesca Conradie
Journal: JAMA Network Open (2024)

Importance Rifampin-resistant tuberculosis treatment regimens require electrocardiographic (ECG) monitoring due to the use of multiple QTc-prolonging agents. Formal 12-lead ECG devices represent a significant burden in resource-constrained clinics worldwide and a potential barrier to treatment scale-up in some settings. Objective To evaluate the diagnostic accuracy of a handheld 6-lead ECG device within resource-constrained clinics. Design, Setting, and Participants This diagnostic study was performed within a multicenter, pragmatic (broad eligibility criteria with no exclusions for randomized participants), phase 3 rifampin-resistant tuberculosis treatment trial (BEAT Tuberculosis [Building Evidence for Advancing New Treatment for Tuberculosis]) in South Africa. A total of 192 consecutive trial participants were assessed, and 191 were recruited for this substudy between January 21, 2021, and March 27, 2023. A low proportion (3 of 432 [0.7%]) of all screened trial participants were excluded due to a QTc interval greater than 450 milliseconds. Triplicate reference standard 12-lead ECG results were human calibrated with readers blinded to 6-lead ECG results. Main Outcomes and Measures Diagnostic accuracy, repeatability, and feasibility of a 6-lead ECG device. Results A total of 191 participants (median age, 36 years [IQR, 28-45 years]; 81 female participants [42.4%]; 91 participants [47.6%] living with HIV) with a median of 4 clinic visits (IQR, 3-4 visits) contributed 2070 and 2015 12-lead and 6-lead ECG assessments, respectively. Across 170 participants attending 489 total clinic visits where valid triplicate QTc measurements were available for both devices, the mean 12-lead QTc measurement was 418 milliseconds (range, 321-519 milliseconds), and the mean 6-lead QTc measurement was 422 milliseconds (range, 288-574 milliseconds; proportion of variation explained, R 2 = 0.4; P &amp;amp;lt; .001). At a QTc interval threshold of 500 milliseconds, the 6-lead ECG device had a negative predictive value of 99.8% (95% CI, 98.8%-99.9%) and a positive predictive value of 16.7% (95% CI, 0.4%-64.1%). The normal expected range of within-individual variability of the 6-lead ECG device was high (±50.2 milliseconds [coefficient of variation, 6.0%]) relative to the 12-lead ECG device (±22.0 milliseconds [coefficient of variation, 2.7%]). The mean (SD) increase in the 12-lead QTc measurement during treatment was 10.1 (25.8) milliseconds, with 0.8% of clinic visits (4 of 489) having a QTc interval of 500 milliseconds or more. Conclusions and Relevance This study suggests that simplified, handheld 6-lead ECG devices are effective triage tests that could reduce the need to perform 12-lead ECG monitoring in resource-constrained settings.
Longitudinal Interplay Between Alcohol Use, Mood, and Functioning in Bipolar Spectrum Disorders
Authors: Sarah H. Sperry, Audrey R. Stromberg, Victoria A. Murphy, Carly A. Lasagna, Melvin G. McInnis, Margo W. Menkes, Anastasia K. Yocum, Ivy F. Tso
Journal: JAMA Network Open (2024)

Importance Alcohol use disorder (AUD) is present in nearly half of individuals with bipolar disorder (BD) and is associated with markedly worsening outcomes. Yet, the concurrent treatment of BD and AUD remains neglected in both research and clinical care; characterizing their dynamic interplay is crucial in improving outcomes. Objective To characterize the longitudinal alcohol use patterns in BD and examine the temporal associations among alcohol use, mood, anxiety, and functioning over time. Design, Setting, and Participants This cohort study selected participants and analyzed data from the Prechter Longitudinal Study of Bipolar Disorder (PLS-BD), an ongoing cohort study that recruits through psychiatric clinics, mental health centers, and community outreach events across Michigan and collects repeated phenotypic data. Participants selected for the present study were those with a diagnosis of BD type I (BDI) or type II (BDII) who had been in the study for at least 5 years. Data used were extracted from February 2006 to April 2022, and follow-up ranged from 5 to 16 years. Main Outcomes and Measures Alcohol use was measured using the Alcohol Use Disorders Identification Test. Depression, mania or hypomania, anxiety, and functioning were measured using the 9-Item Patient Health Questionnaire, the Altman Self-Rating Mania Scale, the 7-item Generalized Anxiety Disorder assessment scale, and the Life Functioning Questionnaire, respectively. Results A total of 584 individuals (386 females (66.1%); mean [SD] age, 40 [13.6] years) were included. These participants had a BDI (445 [76.2%]) or BDII (139 [23.8%]) diagnosis, with or without a lifetime diagnosis of AUD, and a median (IQR) follow-up of 9 (0-16) years. More problematic alcohol use was associated with worse depressive (β = 0.04; 95% credibility interval [CrI], 0.01-0.07) and manic or hypomanic symptoms (β = 0.04; 95% CrI, 0.01-0.07) as well as lower workplace functioning (β = 0.03; 95% CrI, 0.00-0.06) over the next 6 months, but increased depressive and manic or hypomanic symptoms were not associated with greater subsequent alcohol use. These latter 2 associations were more pronounced in BDII than BDI (mania or hypomania: β = 0.16 [95% CrI, 0.02-0.30]; workplace functioning: β = 0.26 [95% CrI, 0.06-0.45]). Alcohol use was not associated with anxiety over time. Conclusions and Relevance This study found that alcohol use, regardless of diagnostic status, was associated with mood instability and poorer work functioning in BD, but increased mood symptoms were not associated with subsequent alcohol use. Given its prevalence and repercussions, dimensional and longitudinal assessment and management of alcohol use are necessary and should be integrated into research and standard treatment of BD.
Prevalence of Iron Deficiency Using 3 Definitions Among Women in the US and Canada
Authors: James C. Barton, Howard W. Wiener, Jackson C. Barton, Ronald T. Acton
Journal: JAMA Network Open (2024)

Importance The prevalence of iron deficiency varies widely according to how it is defined. Objective To compare the prevalence of iron deficiency among women using 3 different definitions. Design, Setting, and Participants The cross-sectional Hemochromatosis and Iron Overload Screening Study (HEIRS; 2000-2006) evaluated the prevalence, determinants, and outcomes of hemochromatosis and other iron-related disorders. Multiethnic, primary care–based screening (2001-2003) was performed at 5 field centers (4 in the US and 1 in Canada). Volunteer women aged 25 years and older were recruited at primary care venues associated with the field centers. Data were analyzed from June to December 2023. Main Outcomes and Measures Measures included transferrin saturation, serum ferritin level, and self-reported age, pregnancy, and race and ethnicity. Three iron deficiency definitions were studied: (1) combined transferrin saturation less than 10% and serum ferritin less than 15 ng/mL (HEIRS), (2) serum ferritin less than 15 ng/mL (World Health Organization [WHO]), and (3) serum ferritin less than 25 ng/mL (a threshold for iron-deficient erythropoiesis [IDE]). Results Among 62 685 women (mean [SD] age, 49.58 [14.27] years), 1957 women (3.12%) had iron deficiency according to the HEIRS definition, 4659 women (7.43%) had iron deficiency according to the WHO definition, and 9611 women (15.33%) had iron deficiency according to the IDE definition. Among 40 381 women aged 25 to 54 years, 1801 women (4.46%) had iron deficiency according to HEIRS, 4267 women (10.57%) had iron deficiency according to WHO, and 8573 women (21.23%) had iron deficiency according to IDE. Prevalence rates of iron deficiency among 2039 women aged 25 to 44 years who reported pregnancy were 5.44% (111 women) according to HEIRS, 18.05% (368 women) according to WHO, and 36.10% (736 women) according to IDE. Iron deficiency prevalence by the 3 respective definitions increased significantly in each racial and ethnic group and was significantly higher among Black and Hispanic participants than Asian and White participants. The relative iron deficiency prevalence among the 62 685 women increased 2.4-fold (95% CI, 2.3-2.5; P &amp;amp;lt; .001) using the WHO definition and increased 4.9-fold (95% CI, 4.7-5.2; P &amp;amp;lt; .001) using the IDE definition. Conclusions and Relevance Three definitions of iron deficiency were associated with significantly different prevalence of iron deficiency in women, regardless of self-reported age, pregnancy, or race and ethnicity. Using higher serum ferritin thresholds to define iron deficiency could lead to diagnosis and treatment of more women with iron deficiency and greater reduction of related morbidity.
Reactive oxygen species regulation by NCF1 governs ferroptosis susceptibility of Kupffer cells to MASH
Authors: Jing Zhang, Yu Wang, Meiyang Fan, Yanglong Guan, Wentao Zhang, Fumeng Huang, Zhengqiang Zhang, Xiaomeng Li, Bingyu Yuan, Wenbin Liu, Manman Geng, Xiaowei Li, Jing Xu, Congshan Jiang, Wenjuan Zhao, Feng Ye, Wenhua Zhu, Liesu Meng, Shemin Lu, Rikard Holmdahl
Journal: Cell Metabolism (2024)
Missense mutations in Myc Box I influence nucleocytoplasmic transport to promote leukemogenesis.
Authors: Nancy B.J. Arthur, Keegan A. Christensen, Kathleen Mannino, Marianna B. Ruzinova, Ashutosh Kumar, Agata Gruszczynska, Ryan B. Day, Petra Erdmann-Gilmore, Yiling Mi, Robert Sprung, Conner R. York, Robert R. Townsend, David H. Spencer, Stephen M. Sykes, Francesca Ferraro
Journal: Clinical Cancer Research (2024)

Abstract Purpose: Somatic missense mutations in the phosphodegron domain of the MYC gene (MYC Box I or MBI) are detected in the dominant clones of a subset of patients with acute myeloid leukemia (AML), but the mechanisms by which they contribute to AML are unknown. Experimental Design: To investigate the effects of MBI MYC mutations on hematopoietic cells, we employed a multi-omic approach to systematically compare the cellular and molecular consequences of expressing oncogenic doses of wild type, threonine-58 and proline-59 mutant MYC proteins in hematopoietic cells, and we developed a knockin mouse harboring the germline MBI mutation p.T58N in the Myc gene. Results: Both wild-type and MBI mutant MYC proteins promote self-renewal programs and expand highly selected subpopulations of progenitor cells in the bone marrow. Compared with their wild-type counterparts, mutant cells display decreased cell death and accelerated leukemogenesis in vivo, changes that are recapitulated in the transcriptomes of human AML-bearing MYC mutations. The mutant phenotypes feature decreased stability and translation of mRNAs encoding proapoptotic and immune-regulatory genes, increased translation of RNA binding proteins and nuclear export machinery, and distinct nucleocytoplasmic RNA profiles. MBI MYC mutant proteins also show a higher propensity to aggregate in perinuclear regions and cytoplasm. Like the overexpression model, heterozygous p.T58N knockin mice displayed similar changes in subcellular MYC localization, progenitor expansion, transcriptional signatures, and develop hematopoietic tumors. Conclusions: This study uncovers that MBI MYC mutations alter RNA nucleocytoplasmic transport mechanisms to contribute to the development of hematopoietic malignancies.
A Histopathologic Correlation Study Evaluating Glymphatic Function in Brain Tumors by Multi-Parametric MRI
Authors: Min Gao, Zhengliang Liu, HongJing Zang, Xiong Wu, Yizhong Yan, Hai Lin, Jianmin Yuan, Tianming Liu, Yu Zhou, Jun Liu
Journal: Clinical Cancer Research (2024)

This study aimed to elucidate the impact of brain tumors on cerebral edema and glymphatic drainage, leveraging advanced imaging techniques to explore the relationship between tumor characteristics, glymphatic function, and aquaporin 4 (AQP4) expression.
An unsupervised learning model based on CT radiomics features accurately predicts axillary lymph node metastasis in breast cancer patients—diagnostic study
Authors: Limeng Qu, Xilong Mei, Zixi Yi, Qiongyan Zou, Qin Zhou, Danhua Zhang, Meirong Zhou, Lei Pei, Qian Long, Jiahao Meng, Huashan Zhang, Qitong Chen, Wenjun Yi
Journal: International Journal of Surgery (2024)

Background: The accuracy of traditional clinical methods for assessing the metastatic status of axillary lymph nodes (ALNs) is unsatisfactory. In this study, the authors propose the use of radiomic technology and three-dimensional (3D) visualization technology to develop an unsupervised learning model for predicting axillary lymph node metastasis in patients with breast cancer (BC), aiming to provide a new method for clinical axillary lymph node assessment in patients with this disease. Methods: In this study, we retrospectively analyzed the data of 350 patients with invasive BC who underwent lung-enhanced computed tomography (CT) and axillary lymph node dissection surgery at the Department of Breast Surgery of the Second Xiangya Hospital of Central South University. The authors used 3D visualization technology to create a 3D atlas of ALNs and identified the region of interest for the lymph nodes. Radiomic features were subsequently extracted and selected, and a prediction model for ALNs was constructed using the K-means unsupervised algorithm. To validate the model, the authors prospectively collected data from 128 BC patients who were clinically evaluated as negative at our center. Results: Using 3D visualization technology, we extracted and selected a total of 36 CT radiomics features. The unsupervised learning model categorized 1737 unlabeled lymph nodes into two groups, and the analysis of the radiomic features between these groups indicated potential differences in lymph node status. Further validation with 1397 labeled lymph nodes demonstrated that the model had good predictive ability for axillary lymph node status, with an area under the curve of 0.847 (0.825–0.869). Additionally, the model’s excellent predictive performance was confirmed in the 128 axillary clinical assessment negative cohort (cN0) and the 350 clinical assessment positive (cN+) cohort, for which the correct classification rates were 86.72 and 87.43%, respectively, which were significantly greater than those of clinical assessment methods. Conclusions: The authors created an unsupervised learning model that accurately predicts the status of ALNs. This approach offers a novel solution for the precise assessment of ALNs in patients with BC.