tbuckley/cabot-search huggingface dataset:
Dietary fiber guar gum-induced shift in gut microbiota metabolism and intestinal immune activity enhances susceptibility to colonic inflammation
Authors: Devendra Paudel, Divek V. T. Nair, Sangshan Tian, Fuhua Hao, Umesh K. Goand, Grace Joseph, Eleni Prodes, Zhi Chai, Chloé E.M. Robert, Benoit Chassaing, Andrew D. Patterson, Vishal Singh
Journal: Gut Microbes (2024)

With an increasing interest in dietary fibers (DFs) to promote intestinal health and the growth of beneficial gut bacteria, there is a continued rise in the incorporation of refined DFs in processed foods. It is still unclear how refined fibers, such as guar gum, affect the gut microbiota activity and pathogenesis of inflammatory bowel disease (IBD). Our study elucidated the effect and underlying mechanisms of guar gum, a fermentable DF (FDF) commonly present in a wide range of processed foods, on colitis development. We report that guar gum containing diet (GuD) increased the susceptibility to colonic inflammation. Specifically, GuD-fed group exhibited severe colitis upon dextran sulfate sodium (DSS) administration, as evidenced by reduced body weight, diarrhea, rectal bleeding, and shortening of colon length compared to cellulose-fed control mice. Elevated levels of pro-inflammatory markers in both serum [serum amyloid A (SAA), lipocalin 2 (Lcn2)] and colon (Lcn2) and extensive disruption of colonic architecture further affirmed that GuD-fed group exhibited more severe colitis than control group upon DSS intervention. Amelioration of colitis in GuD-fed group pre-treated with antibiotics suggest a vital role of intestinal microbiota in GuD-mediated exacerbation of intestinal inflammation. Gut microbiota composition and metabolite analysis in fecal and cecal contents, respectively, revealed that guar gum primarily enriches Actinobacteriota, specifically Bifidobacterium. Guar gum also altered multiple genera belonging to phyla Bacteroidota and Firmicutes. Such shift in gut microbiota composition favored luminal accumulation of intermediary metabolites succinate and lactate in the GuD-fed mice. Colonic IL-18 and tight junction markers were also decreased in the GuD-fed group. Importantly, GuD-fed mice pre-treated with recombinant IL-18 displayed attenuated colitis. Collectively, unfavorable changes in gut microbiota activity leading to luminal accumulation of lactate and succinate, reduced colonic IL-18, and compromised gut barrier function following guar gum feeding contributed to increased colitis susceptibility.
A randomized double-blind, placebo-controlled trial to evaluate the safety and efficacy of live <i>Bifidobacterium longum</i> CECT 7347 (ES1) and heat-treated <i>Bifidobacterium longum</i> CECT 7347 (HT-ES1) in participants with diarrhea-predominant irritable bowel syndrome
Authors: S Srivastava, U Basak, M Naghibi, V Vijayakumar, R Parihar, J Patel, PS Jadon, A Pandit, RR Dargad, S Khanna, S Kumar, R Day
Journal: Gut Microbes (2024)

To determine the efficacy of the probiotic Bifidobacterium longum CECT 7347 (ES1) and postbiotic heat-treated Bifidobacterium longum CECT 7347 (HT-ES1) in improving symptom severity in adults with diarrhea-predominant irritable bowel syndrome (IBS-D), a randomised, double-blind, placebo-controlled trial with 200 participants split into three groups was carried out. Two capsules of either ES1, HT-ES1 or placebo were administered orally, once daily, for 84 days (12 weeks). The primary outcome was change in total IBS-Symptom Severity Scale (IBS-SSS) score from baseline, compared to placebo. Secondary outcome measures were stool consistency, quality of life, abdominal pain severity and anxiety scores. Safety parameters and adverse events were also monitored. The change in IBS-SSS scores from baseline compared to placebo, reached significance in the ES1 and HT-ES1 group, on Days 28, 56 and 84. The decrease in mean IBS-SSS score from baseline to Day 84 was: ES1 (−173.70 [±75.60]) vs placebo (−60.44 [±65.5]) (p < .0001) and HT-ES1 (−177.60 [±79.32]) vs placebo (−60.44 [±65.5]) (p < .0001). Secondary outcomes included changes in IBS-QoL, APS-NRS, stool consistency and STAI-S and STAI-T scores, with changes from baseline to Day 84 being significant in ES1 and HT-ES1 groups, compared to the placebo group. Both ES1 and HT-ES1 were effective in reducing IBS-D symptom severity, as evaluated by measures such as IBS-SSS, IBS-QoL, APS-NRS, stool consistency, and STAI, in comparison to the placebo. These results are both statistically significant and clinically meaningful, representing, to the best of the authors' knowledge, the first positive results observed for either a probiotic or postbiotic from the same strain, in this particular population.
Laser and Light-Based Therapies for Hirsutism Management in Women With Polycystic Ovarian Syndrome
Authors: Katrina Tan, Thisara Coster, Aya Mousa, Adrian Mar, Terhi Piltonen, Jacqueline A. Boyle, Helena Teede, Anju Joham, Daniela Romualdi, Chau Thien Tay
Journal: JAMA Dermatology (2024)

Hirsutism represents a significant concern for women with polycystic ovary syndrome (PCOS), with deleterious psychological effects warranting acknowledgment and a clear imperative to provide effective management. To our knowledge, this is the first review to exclusively examine the effectiveness of laser and light-based therapies in addressing hirsutism in women with PCOS.
Digital Mental Health’s Unstable Dichotomy—Wellness and Health
Authors: John Torous, Joseph Firth, Simon B. Goldberg
Journal: JAMA Psychiatry (2024)

This Viewpoint discusses the unacknowledged risks and harms and unrealized clinical benefits of digital mental wellness and health technologies and offers suggestions for ways to catalyze the next phase of these technologies by focusing on safety, evidence, and engagement.
Examining Sex Differences in Autism Heritability
Authors: Sven Sandin, Benjamin H. K. Yip, Weiyao Yin, Lauren A. Weiss, Joseph D. Dougherty, Stuart Fass, John N. Constantino, Zhu Hailin, Tychele N. Turner, Natasha Marrus, David H. Gutmann, Stephan J. Sanders, Benjamin Christoffersson
Journal: JAMA Psychiatry (2024)

Autism spectrum disorder (ASD) is a neurodevelopmental disorder more prevalent in males than in females. The cause of ASD is largely genetic, but the association of genetics with the skewed sex ratio is not yet understood. To our knowledge, no large population-based study has provided estimates of heritability by sex.
Drug Survival of IL-17 and IL-23 Inhibitors for Psoriasis: A Systematic Review and Meta-Analysis
Authors: Sarah E. Thomas, Liana Barenbrug, Gerjon Hannink, Marieke M. B. Seyger, Elke M. G. J. de Jong, Juul M. P. A. van den Reek
Journal: Drugs (2024)

The most recently approved biologics for moderate-to-severe psoriasis are the interleukin (IL)-17 and IL-23 inhibitors. Drug survival is a frequently used outcome to assess drug performance in practice. An overview of the available drug survival studies regarding IL-17 and IL-23 inhibitors is lacking. Therefore, our objective was to assess the drug survival of IL-17 and IL-23 inhibitors for psoriasis.
Weekly Pulsed Dye Laser Treatments for Port-Wine Birthmarks in Infants
Authors: Shirin Bajaj, Joy Tao, David A. Hashemi, Roy G. Geronemus
Journal: JAMA Dermatology (2024)

Early treatment of port-wine birthmark (PWB) can be life-altering and is often associated with improved outcomes and quality of life. There is growing evidence that shorter treatment intervals may play a role in more rapid PWB clearance; however, the optimal treatment interval has not been established.
Tirzepatide for Maintenance of Weight Reduction in Adults With Obesity
Authors: Yifan Xiao, Jiahao Meng, Shuguang Gao
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
Pregnancy and Cancer—Navigating Impossible Decisions
Authors: Alisa Kachikis, Linda O. Eckert
Journal: JAMA Network Open (2024)

Paul Gougis, MD; Anne-Sophie Hamy, MD, PhD; Floriane Jochum, MD; Kevin Bihan, PharmD; Marie Carbonnel, MD; Joe-Elie Salem, MD, PhD; Elise Dumas, PhD; Rayan Kabirian, MD; Beatriz Grandal, MD, PhD; Solenn Barraud, MD; Florence Coussy, MD, PhD; Judicael Hotton, MD; Raphaelle Savarino, MD; Aurélien Marabelle, MD, PhD; Jacques Cadranel, MD, PhD; Jean-Philippe Spano, MD, PhD; Enora Laas, MD; Fabien Reyal, MD, PhD; Baptiste Abbar, MD
Sirtuins and Cellular Senescence in Patients with Idiopathic Pulmonary Fibrosis and Systemic Autoimmune Disorders
Authors: Vito D’Agnano, Domenica Francesca Mariniello, Raffaella Pagliaro, Mehrdad Savabi Far, Angela Schiattarella, Filippo Scialò, Giulia Stella, Maria Gabriella Matera, Mario Cazzola, Andrea Bianco, Fabio Perrotta
Journal: Drugs (2024)

The sirtuin family is a heterogeneous group of proteins that play a critical role in many cellular activities. Several degenerative diseases have recently been linked to aberrant sirtuin expression and activity because of the involvement of sirtuins in maintaining cell longevity and their putative antiaging function. Idiopathic pulmonary fibrosis and progressive pulmonary fibrosis associated with systemic autoimmune disorders are severe diseases characterized by premature and accelerated exhaustion and failure of alveolar type II cells combined with aberrant activation of fibroblast proliferative pathways leading to dramatic destruction of lung architecture. The mechanisms underlying alveolar type II cell exhaustion in these disorders are not fully understood. In this review, we have focused on the role of sirtuins in the pathogenesis of idiopathic and secondary pulmonary fibrosis and their potential as biomarkers in the diagnosis and management of fibrotic interstitial lung diseases.
Hospitalization and Continuity of Care in Anti-MDA5 Dermatomyositis
Authors: William Mark Richardson, Jill T. Shah, Daniel R. Mazori, Avrom S. Caplan, Kristen I. Lo Sicco, Alisa N. Femia
Journal: JAMA Dermatology (2024)

This cohort study describes the clinical features, patient characteristics, and treatment of anti-melanoma differentiation–associated gene 5 (MDA5) dermatomyositis.
Clopidogrel Monotherapy for Double-Risk Acute Coronary Syndrome
Authors: Marco Valgimigli, Antonio Landi
Journal: JAMA Cardiology (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 Cardiology 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 Cardiology journal
Tirzepatide for Maintenance of Weight Reduction in Adults With Obesity—Reply
Authors: Louis J. Aronne
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
Novel germline <scp><i>JAK2</i><sup>R715T</sup></scp> mutation causing <scp>PV</scp>‐like erythrocytosis in 3 generations. Amelioration by Ropeg‐Interferon
Authors: Jihyun Song, Lucie Lanikova, Soo Jin Kim, Nicolas Papadopoulos, Jessica Meznarich, Stefan N. Constantinescu, Brynn Parsegov, Jaroslav F. Prchal, Josef T. Prchal
Journal: American Journal of Hematology (2024)

Abstract Polycythemia vera (PV) is a clonal disorder arising from the acquired somatic mutations of the JAK2 gene, including JAK2 V617F or several others in exon 12. A 38‐year‐old female had a stroke at age 32 and found to have elevated hemoglobin, normal leukocytes, normal platelets, and tested negative for JAK2 V617F and exon 12 mutations. Next generation sequencing revealed a novel mutation: JAK2 R715T in the pseudokinase domain (JH2) at 47.5%. Its presence in her nail DNA confirmed a germline origin. Her mother and her son similarly had erythrocytosis and a JAK2 R715T mutation. Computer modeling indicated gain‐of‐function JAK2 activity. The propositus and her mother had polyclonal myelopoiesis, ruling out another somatic mutation‐derived clonal hematopoiesis. Some erythroid progenitors of all three generations grew without erythropoietin, a hallmark of PV. The in vitro reporter assay confirmed increased activity of the JAK2 R715T kinase. Similar to PV, the JAK2 R715T native cells have increased STAT5 phosphorylation, augmented transcripts of prothrombotic and inflammatory genes, and decreased KLF2 transcripts. The propositus was not controlled by hydroxyurea, and JAK2 inhibitors were not tolerated; however, Ropeginterferon‐alfa‐2b (Ropeg‐IFN‐α) induced a remission. Ropeg‐IFN‐α treatment also reduced JAK2 activity in the propositus, her mother and JAK2 V617F PV subjects. We report dominantly inherited erythrocytosis secondary to a novel germline JAK2 R715T gain‐of‐function mutation with many but not all comparable molecular features to JAK2 V617F PV. We also document a previously unreported inhibitory mechanism of JAK2 signaling by Ropeg‐IFN‐α.
Comparing serial and current liver stiffness measurements to predict decompensation in compensated advanced chronic liver disease patients
Authors: Yu Jun Wong, Vincent L. Chen, Asim Abdulhamid, Giulia Tosetti, Huttakan Navadurong, Apichat Kaewdech, Jessica Cristiu, Michael Song, Pooja Devan, Kai Le Ashley Tiong, Jean Ee Neo, Thaninee Prasoppokakorn, Pimsiri Sripongpun, Catherine Ann Malcolm Stedman, Sombat Treeprasertsuk, Massimo Primignani, Jing Hieng Ngu, Juan G. Abraldes
Journal: Hepatology (2024)

Background and Aims: The utility of serial liver stiffness measurements (LSM) to predict decompensation in patients with compensated advanced chronic liver disease (cACLD) remains unclear. We aimed to validate whether comparing serial LSM is superior to using the current LSM to predict liver-related events (LRE) in patients with cACLD. Approach and Results: In this retrospective analysis of an international registry, patients with cACLD and serial LSM were followed up until index LRE. We compared the performance of both the dynamic LSM changes and the current LSM in predicting LRE using Cox regression analysis, considering time zero of follow-up as the date of latest liver stiffness measurement. In all, 480 patients with cACLD with serial LSM were included from 5 countries. The commonest etiology of cACLD was viral (53%) and MASLD (34%). Over a median follow-up of 68 (IQR: 45 -92) months, 32% experienced a LSM decrease to levels below 10kPa (resolved cACLD) and 5.8% experienced LRE. Resolved cACLD were more likely to be nondiabetic and had better liver function. While a higher value of the current LSM was associated with higher LREs, LSM changes over time (LSM slope) were not associated with LRE. In multivariable Cox regression, neither the prior LSM nor the LSM slope added predictive value to latest liver stiffness measurement. Conclusions: Once the current LSM is known, previous LSM values do not add to the prediction of LREs in patients with cACLD.
Erenumab for Treatment of Persistent Erythema and Flushing in Rosacea
Authors: Nita K. F. Wienholtz, Casper E. Christensen, Thien P. Do, Lith E. W. Frifelt, Josefin Snellman, Cristina L. Lopez-Lopez, Alexander Egeberg, Jacob P. Thyssen, Messoud Ashina
Journal: JAMA Dermatology (2024)

Treatment of erythema and flushing in rosacea is challenging. Calcitonin gene-related peptide (CGRP) has been associated with the pathogenesis of rosacea, raising the possibility that inhibition of the CGRP pathway might improve certain features of the disease.
Unmet Needs, Quality of Life, and Financial Toxicity Among Survivors of Lung Cancer
Authors: Melinda L. Hsu, Mary C. Boulanger, Sarah Olson, Cyd Eaton, Laura Prichett, Matthew Guo, Mattea Miller, Julie Brahmer, Patrick M. Forde, Kristen A. Marrone, Michelle Turner, Josephine L. Feliciano
Journal: JAMA Network Open (2024)

Importance Despite a growing population of survivors of lung cancer, there is limited understanding of the survivorship journey. Survivors of lung cancer experience unmet physical, social, emotional, and medical needs regardless of stage at diagnosis or treatment modalities. Objective To investigate the association of unmet needs with quality of life (QOL) and financial toxicity (FT) among survivors of lung cancer. Design, Setting, and Participants This survey study was conducted at Johns Hopkins Sidney Kimmel Comprehensive Cancer Center thoracic oncology clinics between December 1, 2020, and September 30, 2021, to assess needs (physical, social, emotional, and medical), QOL, and FT among survivors of lung cancer. Patients had non–small cell lung cancer of any stage and were alive longer than 1 year from diagnosis. A cross-sectional survey was administered, which consisted of an adapted needs survey developed by the Mayo Survey Research Center, the Comprehensive Score for Financial Toxicity measure, and the European Organization for Research and Treatment of Cancer QLQ-C30 QOL scale. Demographic and clinical information was obtained through retrospective medical record review. Data analysis was performed between May 9 and December 8, 2022. Main Outcomes and Measures Separate multiple linear regression models, treating QOL and FT as dependent variables, were performed to assess the adjusted association of total number of unmet needs and type of unmet need (physical, emotional, social, or medical) with QOL and FT. Results Of the 360 survivors of lung cancer approached, 232 completed the survey and were included in this study. These 232 respondents had a median age of 69 (IQR, 60.5-75.0) years. Most respondents were women (144 [62.1%]), were married (165 [71.1%]), and had stage III or IV lung cancer (140 [60.3%]). Race and ethnicity was reported as Black (33 [14.2%]), White (172 [74.1%]), or other race or ethnicity (27 [11.6%]). A higher number of total unmet needs was associated with lower QOL (β [SE], −1.37 [0.18]; P &amp;amp;lt; .001) and higher FT (β [SE], −0.33 [0.45]; P &amp;amp;lt; .001). In the context of needs domains, greater unmet physical needs (β [SE], −1.24 [0.54]; P = .02), social needs (β [SE], −3.60 [1.34]; P = .01), and medical needs (β [SE], −2.66 [0.98]; P = .01) were associated with lower QOL, whereas only greater social needs was associated with higher FT (β [SE], −3.40 [0.53]; P &amp;amp;lt; .001). Conclusions and Relevance The findings of this survey study suggest that among survivors of lung cancer, unmet needs were associated with lower QOL and higher FT. Future studies evaluating targeted interventions to address these unmet needs may improve QOL and FT among survivors of lung cancer.
Treatment Failure and Long-Term Prescription Risk for Guideline-Recommended Hypnotics in Japan
Authors: Masahiro Takeshima, Kazuhisa Yoshizawa, Masaya Ogasawara, Mizuki Kudo, Yu Itoh, Naoko Ayabe, Kazuo Mishima
Journal: JAMA Network Open (2024)

Although insomnia guidelines recommend the use of several individual hypnotics, the most useful hypnotic for treating insomnia in a clinical setting remains unclear.
Bone marrow <i>Tfr2</i> deletion improves the therapeutic efficacy of the activin‐receptor ligand trap RAP‐536 in β‐thalassemic mice
Authors: Emanuele Tanzi, Simona Maria Di Modica, Jessica Bordini, Violante Olivari, Alessia Pagani, Valeria Furiosi, Laura Silvestri, Alessandro Campanella, Antonella Nai
Journal: American Journal of Hematology (2024)

Abstract β‐thalassemia is a disorder characterized by anemia, ineffective erythropoiesis (IE), and iron overload, whose treatment still requires improvement. The activin receptor‐ligand trap Luspatercept, a novel therapeutic option for β‐thalassemia, stimulates erythroid differentiation inhibiting the transforming growth factor β pathway. However, its exact mechanism of action and the possible connection with erythropoietin ( Epo ), the erythropoiesis governing cytokine, remain to be clarified. Moreover, Luspatercept does not correct all the features of the disease, calling for the identification of strategies that enhance its efficacy. Transferrin receptor 2 (TFR2) regulates systemic iron homeostasis in the liver and modulates the response to Epo of erythroid cells, thus balancing red blood cells production with iron availability. Stimulating Epo signaling, hematopoietic Tfr2 deletion ameliorates anemia and IE in Hbb th3 / + thalassemic mice. To investigate whether hematopoietic Tfr2 inactivation improves the efficacy of Luspatercept, we treated Hbb th3 / + mice with or without hematopoietic Tfr2 ( Tfr2 BMKO /Hbb th3 / + ) with RAP‐536, the murine analog of Luspatercept. As expected, both hematopoietic Tfr2 deletion and RAP‐536 significantly ameliorate IE and anemia, and the combined approach has an additive effect. Since RAP‐536 has comparable efficacy in both Hbb th3/+ and Tfr2 BMKO /Hbb th3/+ animals, we propose that the drug promotes erythroid differentiation independently of TFR2 and EPO stimulation. Notably, the lack of Tfr2 , but not RAP‐536, can also attenuate iron‐overload and related complications. Overall, our results shed further light on the mechanism of action of Luspatercept and suggest that strategies aimed at inhibiting hematopoietic TFR2 might improve the therapeutic efficacy of activin receptor‐ligand traps.