tbuckley/cabot-search huggingface dataset:
Mortality Among Individuals With Hypochondriasis—Reply
Authors: David Mataix-Cols, Paul Lichtenstein, Erik Hedman-Lagerlöf
Journal: JAMA Psychiatry (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 Psychiatry 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 Psychiatry journal
Hyperhidrosis and Hypermobility Spectrum Disorders Among Adolescents
Authors: Yair Zloof, Estela Derazne, Maya Braun, Rivka Friedland, Oded Scheuerman, Amir Shlaifer, Lotem Goldberg
Journal: JAMA Dermatology (2024)

This cross-sectional study assesses the prevalence and risk of excessive sweating and joint hypermobility in Israeli adolescents aged 16 to 19 years.
Patient-Reported Adverse Events and Early Treatment Discontinuation Among Patients With Multiple Myeloma
Authors: John Devin Peipert, Fengmin Zhao, Ju-Whei Lee, Shu-en Shen, Edward Ip, Nathaniel O’Connell, Ruth C. Carlos, Noah Graham, Mary Lou Smith, Ilana F. Gareen, Pamela J. Raper, Matthias Weiss, Shaji K. Kumar, S. Vincent Rajkumar, David Cella, Robert Gray, Lynne I. Wagner
Journal: JAMA Network Open (2024)

Importance There is substantial interest in capturing cancer treatment tolerability from the patient’s perspective using patient-reported outcomes (PROs). Objective To examine whether a PRO question, item 5 from the Functional Assessment of Cancer Therapy-General General Physical Wellbeing Scale (GP5), was associated with early treatment discontinuation (ETD) due to adverse events. Design, Setting, and Participants This prospective survey study was conducted from February to April 2023. Among participants in the ECOG-ACRIN E1A11 trial (a phase 3, parallel design trial conducted between 2013 and 2019), patients with newly diagnosed multiple myeloma were randomized to receive bortezomib (VRd) or carfilzomib (KRd) plus lenalidomide and dexamethasone as induction therapy. The GP5 item was administered at baseline (pretreatment) and at 1 month, 2.8 months, and 5.5 months postbaseline. Eligible participants included patients with newly diagnosed multiple myeloma treated at community oncology practices or academic medical centers in the US. Exposures GP5 response options were “very much,” “quite a bit,” “somewhat,” “a little bit,” and “not at all.” Responses at each assessment while undergoing treatment (1 month, 2.8 months, and 5.5 months) were categorized as high adverse event bother (ie, “very much,” and “quite a bit”) and low adverse event bother (ie, “somewhat,” “a little bit,” or “not at all”). In addition, change from baseline to each assessment while undergoing treatment was calculated and categorized as worsening by 1 response category and 2 or more response categories. Main Outcome and Measure ETD due to adverse events (yes vs no) was analyzed using logistic regression adjusting for treatment group, performance status, gender, race, and disease stage. Results Of the 1087 participants in the original trial, 1058 (mean [SD] age 64 [9] years; 531 receiving VrD [50.2%]; 527 receiving KRd [49.8%]) responded to item GP5 and were included in the secondary analysis. A small proportion (142 patients [13.4%]) discontinued treatment early due to AEs. For those with high adverse-effect bother, GP5 while undergoing treatment was associated with ETD at 1 month (adjusted odds ratio [aOR], 2.20; 95% CI, 1.25-3.89), 2.8 months (aOR, 3.41; 95% CI, 2.01-5.80), and 5.5 months (aOR, 4.66; 95% CI, 1.69-12.83). Worsening by 2 or more response categories on the GP5 was associated with ETD at 2.8 months (aOR, 3.02; 95% CI, 1.64-5.54) and 5.5 months (aOR, 5.49; 95% CI, 1.45-20.76). Conclusions and Relevance In this survey study of the E1A11 trial, worse GP5 response was associated with ETD. These findings suggest that simple assessment of adverse-effect bother while receiving treatment is an efficient way to indicate treatment tolerability and ETD risk.
m6A modification promotes EMT and metastasis of castration-resistant prostate cancer by upregulating NFIB
Authors: Feng Shu, Hao Liu, Xiaohui Chen, Ye Liu, Jiangli Zhou, Lei Tang, Wanwei Cao, Shanshan Yang, Yili Long, Rongna Li, Hao Wang, Hongsheng Wang, Guanmin Jiang
Journal: Cancer Research (2024)

The widespread use of androgen receptor (AR) signaling inhibitors has led to an increased incidence of AR-negative castration-resistant prostate cancer (CRPC), limiting effective treatment and patient survival. A more comprehensive understanding of the molecular mechanisms supporting AR-negative CRPC could reveal therapeutic vulnerabilities to improve treatment. This study showed that the transcription factor nuclear factor I/B (NFIB) was upregulated in patient with AR-negative CRPC tumors and cell lines and was positively associated with an epithelial-to-mesenchymal transition (EMT) phenotype. Loss of NFIB inhibited EMT and reduced migration of CRPC cells. NFIB directly bound to gene promoters and regulated the transcription of EMT-related factors E-cadherin (CDH1) and vimentin (VIM), independent of other typical EMT-related transcriptional factors. In vivo data further supported the positive role of NFIB in the metastasis of AR-negative CRPC cells. Moreover, N6-methyladenosine (m6A) modification induced NFIB upregulation in AR-negative CRPC. Mechanistically, the m6A levels of mRNA, including NFIB and its E3 ubiquitin ligase TRIM8, were increased in AR-negative CRPC cells. Elevated m6A methylation of NFIB mRNA recruited YTHDF2 to increase mRNA stability and protein expression. Inversely, the m6A modification of TRIM8 mRNA, induced by ALKBH5 downregulation, decreased its translation and expression, which further promoted NFIB protein stability. Overall, this study reveals that upregulation of NFIB, mediated by m6A modification, triggers EMT and metastasis in AR-negative CRPC. Targeting the m6A/NFIB axis is a potential prevention and treatment strategy for AR-negative CRPC metastasis.
Risk Assessment and Prevention of Falls in Older Community-Dwelling Adults
Authors: Cathleen S. Colón-Emeric, Cara L. McDermott, Deborah S. Lee, Sarah D. Berry
Journal: JAMA (2024)

Importance Falls are reported by more than 14 million US adults aged 65 years or older annually and can result in substantial morbidity, mortality, and health care expenditures. Observations Falls result from age-related physiologic changes compounded by multiple intrinsic and extrinsic risk factors. Major modifiable risk factors among community-dwelling older adults include gait and balance disorders, orthostatic hypotension, sensory impairment, medications, and environmental hazards. Guidelines recommend that individuals who report a fall in the prior year, have concerns about falling, or have gait speed less than 0.8 to 1 m/s should receive fall prevention interventions. In a meta-analysis of 59 randomized clinical trials (RCTs) in average-risk to high-risk populations, exercise interventions to reduce falls were associated with 655 falls per 1000 patient-years in intervention groups vs 850 falls per 1000 patient-years in nonexercise control groups (rate ratio [RR] for falls, 0.77; 95% CI, 0.71-0.83; risk ratio for number of people who fall, 0.85; 95% CI, 0.81-0.89; risk difference, 7.2%; 95% CI, 5.2%-9.1%), with most trials assessing balance and functional exercises. In a meta-analysis of 43 RCTs of interventions that systematically assessed and addressed multiple risk factors among individuals at high risk, multifactorial interventions were associated with 1784 falls per 1000 patient-years in intervention groups vs 2317 falls per 1000 patient-years in control groups (RR, 0.77; 95% CI, 0.67-0.87) without a significant difference in the number of individuals who fell. Other interventions associated with decreased falls in meta-analysis of RCTs and quasi-randomized trials include surgery to remove cataracts (8 studies with 1834 patients; risk ratio [RR], 0.68; 95% CI, 0.48-0.96), multicomponent podiatry interventions (3 studies with 1358 patients; RR, 0.77; 95% CI, 0.61-0.99), and environmental modifications for individuals at high risk (12 studies with 5293 patients; RR, 0.74; 95% CI, 0.61-0.91). Meta-analysis of RCTs of programs to stop medications associated with falls have not found a significant reduction, although deprescribing is a component of many successful multifactorial interventions. Conclusions and Relevance More than 25% of older adults fall each year, and falls are the leading cause of injury-related death in persons aged 65 years or older. Functional exercises to improve leg strength and balance are recommended for fall prevention in average-risk to high-risk populations. Multifactorial risk reduction based on a systematic clinical assessment for modifiable risk factors may reduce fall rates among those at high risk.
Lepodisiran for Elevated Lipoprotein(a)—Reply
Authors: Steven E. Nissen, Helle Linnebjerg, Stephen J. Nicholls
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
Persistent Cutaneous Lesions of Darier Disease and Second-Hit Somatic Variants in <i>ATP2A2</i> Gene
Authors: Lihi Atzmony, Fadia Zagairy, Banan Mawassi, Majd Shehade, Yasmin Tatour, Nada Danial-Farran, Morad Khayat, Nassim Warrour, Roni Dodiuk-Gad, Eran Cohen-Barak
Journal: JAMA Dermatology (2024)

Importance Darier disease (DD) is a rare genetic skin disorder caused by heterozygous variants in the ATP2A2 gene. Clinical manifestations include recurrent hyperkeratotic papules and plaques that occur mainly in seborrheic areas. Although some of the lesions wax and wane in response to environmental factors, others are severe and respond poorly to therapy. Objective To investigate the molecular mechanism underlying the persistency of skin lesions in DD. Design, Setting, and Participants In this case series, DNA was extracted from unaffected skin, transient and persistent lesional skin, and blood from 9 patients with DD. Genetic analysis was used using paired-whole exome sequencing of affected skin and blood or by deep sequencing of ATP2A2 of affected skin. Chromosomal microarray analysis was used to reveal copy number variants and loss of heterozygosity. All variants were validated by Sanger sequencing or restriction fragment length polymorphism. Interventions or Exposures Paired whole-exome sequencing and deep sequencing of ATP2A2 gene from blood and skin samples isolated from persistent, transient lesions and unaffected skin in patients with DD. Main Outcomes and Measures Germline and somatic genomic characteristics of persistent and transient cutaneous lesions in DD. Results Of 9 patients with DD, all had heterozygous pathogenic germline variants in the ATP2A2 gene, 6 were female. Participant age ranged from 40 to 69 years on enrollment. All 11 persistent skin lesions were associated with second-hit somatic variants in the ATP2A2 gene. The somatic variants were classified as highly deleterious via combined annotation-dependent depletion (CADD) scores or affect splicing, and 3 of them had been previously described in patients with DD and acrokeratosis verruciformis of Hopf. Second-hit variants in the ATP2A2 gene were not identified in the transient lesions (n = 2) or the normal skin (n = 2). Conclusions and Relevance In this study, persistent DD lesions were associated with the presence of second-hit somatic variants in the ATP2A2 gene. Identification of these second-hit variants offers valuable insight into the underlying mechanisms that contribute to the lasting nature of persistent DD lesions.
A Personalized Evolution in Hernia Care
Authors: Jerome C. Anyalebechi, S. Scott Davis
Journal: JAMA Surgery (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 Surgery 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 Surgery journal
Effects of empagliflozin on liver fat in patients with metabolic dysfunction–associated steatotic liver disease without diabetes mellitus: A randomized, double-blind, placebo-controlled trial
Authors: Ka Shing Cheung, Ho Yu Ng, Rex Wan Hin Hui, Lok Ka Lam, Lung Yi Mak, Yuen Chi Ho, Jing Tong Tan, Esther W. Chan, Wai Kay Seto, Man Fung Yuen, Wai K. Leung
Journal: Hepatology (2024)

Background and Aims: We investigated whether empagliflozin reduces hepatic steatosis in patients with metabolic dysfunction–associated steatotic liver disease without diabetes mellitus. Approach and Results: This was an investigator-initiated, double-blind, randomized, placebo-controlled trial recruiting adult subjects from the community. Eligible subjects without diabetes mellitus (fasting plasma glucose &lt; 7 mmol/L and HbA1c &lt; 6.5%) who had magnetic resonance imaging-proton density fat fraction (MRI-PDFF) ≥ 5% were randomly allocated to receive empagliflozin 10 mg daily or placebo (1:1 ratio) for 52 weeks (end of treatment, EOT). MRI-PDFF was conducted at baseline and EOT. The primary outcome was the difference in change of MRI-PDFF between the 2 groups at EOT. Secondary outcomes were hepatic steatosis resolution (MRI-PDFF &lt; 5%), alanine aminotransferase drop ≥ 17 U/L, MRI-PDFF decline ≥ 30%, a combination of both, and changes of anthropometric and laboratory parameters at EOT. All outcomes were based on intention-to-treat analysis. Of 98 recruited subjects (median age: 55.7 y [IQR:49.5–63.4]; male:54 [55.1%]), 97 (empagliflozin:49, placebo:48; median MRI-PDFF:9.7% vs 9.0%) had MRI-PDFF repeated at EOT. The Empagliflozin group had a greater reduction in median MRI-PDFF compared to the placebo group (–2.49% vs. –1.43%; p = 0.025), with a nonsignificant trend of resolution of hepatic steatosis (44.9% vs. 28.6%; p = 0.094). There was no significant difference in alanine aminotransferase drop ≥ 17 U/L (16.3% vs. 12.2%; p = 0.564), MRI-PDFF drop ≥ 30% (49.0% vs. 40.8%; p = 0.417), and composite outcome (8.2% vs. 8.2%; p = 1.000). Empagliflozin group had a greater drop in body weight (–2.7 vs. –0.2 kg), waist circumference (–2.0 vs. 0 cm), fasting glucose (–0.3 vs. 0 mmol/L), and ferritin (–126 vs. –22 pmol/L) (all p &lt; 0.05). Conclusions: Empagliflozin for 52 weeks reduces hepatic fat content in subjects with nondiabetic metabolic dysfunction–associated steatotic liver disease. (ClinicalTrials.gov Identifier: NCT04642261).
No sign of weakness: a systematic review and meta-analysis of hip and calf muscle strength after anterior cruciate ligament injury
Authors: Michael Girdwood, Adam G Culvenor, Brooke Patterson, Melissa Haberfield, Ebonie Kendra Rio, Michael Hedger, Kay M Crossley
Journal: British Journal of Sports Medicine (2024)

Objective We aimed to determine hip and lower-leg muscle strength in people after ACL injury compared with an uninjured control group (between people) and the uninjured contralateral limb (between limbs). Design Systematic review with meta-analysis. Data sources MEDLINE, EMBASE, CINAHL, Scopus, Cochrane CENTRAL and SportDiscus to 28 February 2023. Eligibility criteria Primary ACL injury with mean age 18–40 years at time of injury. Studies had to measure hip and/or lower-leg muscle strength quantitatively (eg, dynamometer) and report muscle strength for the ACL-injured limb compared with: (i) an uninjured control group and/or (ii) the uninjured contralateral limb. Risk of bias was assessed according to Cochrane Collaboration domains. Results Twenty-eight studies were included (n=23 measured strength ≤12 months post-ACL reconstruction). Most examined hip abduction (16 studies), hip extension (12 studies) and hip external rotation (7 studies) strength. We found no meaningful difference in muscle strength between people or between limbs for hip abduction, extension, internal rotation, flexion or ankle plantarflexion, dorsiflexion (estimates ranged from −9% to +9% of comparator). The only non-zero differences identified were in hip adduction (24% stronger on ACL limb (95% CI 8% to 42%)) and hip external rotation strength (12% deficit on ACL limb (95% CI 6% to 18%)) compared with uninjured controls at follow-ups &gt;12 months, however both results stemmed from only two studies. Certainty of evidence was very low for all outcomes and comparisons, and drawn primarily from the first year post-ACL reconstruction. Conclusion Our results do not show widespread or substantial muscle weakness of the hip and lower-leg muscles after ACL injury, contrasting deficits of 10%–20% commonly reported for knee extensors and flexors. As it is unclear if deficits in hip and lower-leg muscle strength resolve with appropriate rehabilitation or no postinjury or postoperative weakness occurs, individualised assessment should guide training of hip and lower-leg strength following ACL injury. PROSPERO registration number CRD42020216793.
Multiple sclerosis endophenotypes identified by high-dimensional blood signatures are associated with distinct disease trajectories
Authors: Catharina C. Gross, Andreas Schulte-Mecklenbeck, Olga V. Steinberg, Timo Wirth, Sarah Lauks, Stefan Bittner, Patrick Schindler, Sergio E. Baranzini, Sergiu Groppa, Judith Bellmann-Strobl, Nora Bünger, Claudia Chien, Eva Dawin, Maria Eveslage, Vinzenz Fleischer, Gabriel Gonzalez-Escamilla, Barbara Gisevius, Jürgen Haas, Martin Kerschensteiner, Lucienne Kirstein, Catharina Korsukewitz, Lisa Lohmann, Jan D. Lünemann, Felix Luessi, Gerd Meyer zu Hörste, Jeremias Motte, Tobias Ruck, Klemens Ruprecht, Nicholas Schwab, Falk Steffen, Sven G. Meuth, Friedemann Paul, Brigitte Wildemann, Tania Kümpfel, Ralf Gold, Tim Hahn, Frauke Zipp, Luisa Klotz, Heinz Wiendl, Orhan Aktas, Ilya Ayzenberg, Erik Bahn, Antonios Bayas, Klaus Berger, Achim Berthele, Wolfgang Brück, Sina Engel, Tim Friede, Christoph Heesen, Kerstin Hellwig, Bernhard Hemmer, Boris Kallmann, Ingo Kleiter, Thomas Korn, Markus Kowarik, Ralf Linker, Carsten Lukas, Mathias Mäurer, Mark Mühlau, Sandra Nischwitz, Anke Salmen, Edda Sauer, Christine Stadelmann-Nessler, Florian Then Bergh, Corinna Trebst, Hayrettin Tumani, Clemens Warnke, Martin S. Weber
Journal: Science Translational Medicine (2024)

One of the biggest challenges in managing multiple sclerosis is the heterogeneity of clinical manifestations and progression trajectories. It still remains to be elucidated whether this heterogeneity is reflected by discrete immune signatures in the blood as a surrogate of disease pathophysiology. Accordingly, individualized treatment selection based on immunobiological principles is still not feasible. Using two independent multicentric longitudinal cohorts of patients with early multiple sclerosis ( n = 309 discovery and n = 232 validation), we were able to identify three distinct peripheral blood immunological endophenotypes by a combination of high-dimensional flow cytometry and serum proteomics, followed by unsupervised clustering. Longitudinal clinical and paraclinical follow-up data collected for the cohorts revealed that these endophenotypes were associated with disease trajectories of inflammation versus early structural damage. Investigating the capacity of immunotherapies to normalize endophenotype-specific immune signatures revealed discrete effect sizes as illustrated by the limited effect of interferon-β on endophenotype 3–related immune signatures. Accordingly, patients who fell into endophenotype 3 subsequently treated with interferon-β exhibited higher disease progression and MRI activity over a 4-year follow-up compared with treatment with other therapies. We therefore propose that ascertaining a patient’s blood immune signature before immunomodulatory treatment initiation may facilitate prediction of clinical disease trajectories and enable personalized treatment decisions based on pathobiological principles.