tbuckley/cabot-search huggingface dataset:
Author Correction: A roadmap for clinical trials in MASH-related compensated cirrhosis
Authors: Juan M. Pericàs, Quentin M. Anstee, Salvador Augustin, Ramón Bataller, Annalisa Berzigotti, Andreea Ciudin, Sven Francque, Juan G. Abraldes, Virginia Hernández-Gea, Mònica Pons, Thomas Reiberger, Ian A. Rowe, Peter Rydqvist, Elmer Schabel, Frank Tacke, Emmanuel A. Tsochatzis, Joan Genescà
Journal: Nature Reviews Gastroenterology & Hepatology (2024)

In the version of the article initially published, the reference Chalasani, N. et al.Effects of belapectin, an inhibitor of galectin-3, in patients with nonalcoholic steatohepatitis with cirrhosis and portal hypertension.Gastroenterol.158 1334-1345 (2020) was missing and has now been added as ref. 111 in the second paragraph of the "HVPG as a surrogate end point" section.Additionally, in the second paragraph of the "Current scenario of clinical trials in MASH" section, the sentence "NAVIGATE (NCT04365868; 357 participants) was a phase IIb-III trial…" has been corrected to "NAVIGATE (NCT04365868; 357 participants) is a phase IIb-III trial…".These corrections have been made to the HTML and PDF versions of the article.
A prospective cohort study on rivaroxaban in the prevention of catheter-related thrombosis in breast cancer.
Authors: Die Sang, Yurong Zhang, Shanmin Fan, Shiyu Li, Yanfang Su, Peng Yuan
Journal: Journal of Clinical Oncology (2024)

e12602 Background: Chemotherapy is an important treatment strategy for breast cancer. Catheter related thrombosis (CRT) is one of the most common complications of catheterization, affecting patients’ living quality and survival. It is thus of great practical significance for exploring how to prevent CRT. That’s why we carried out this study to provide evidence-based medical data for the prevention and treatment of thrombosis in breast cancer patients. Methods: A prospective cohort study approach was adopted. Breast cancer patients who received deep vein catheterization chemotherapy from July 2021 to July 2023 were selected. Cohort A included patients in the treatment group: they received prophylactic anticoagulation after catheterization: Rivaroxaban, 10 mg, orally once/d for 2 months; cohort B included patients in the control group, who did not receive prophylactic anticoagulation. The thrombosis was compared between the patients in the two groups within six months after catheterization. The comparison between groups was tested by X 2 test, and logistic regression analysis was used to analyze the influencing factors of CRT. Results: A total of 402 breast cancer patients were enrolled. The incidence of CRT was 2.0% (4/201) in the treatment group of 201 cases and 12.4% (25/201) in the control group of 201 cases ( P=0.000). The thrombus was mainly located around the axillary vein, basilic vein and subclavian vein, the innominate vein, and the internal jugular vein. There were 44.8% (13/29) patients developed CRT within 30 days after catheterization, 20.7% (6/29) patients developed CRT within 30~&lt;60days, and 34.5% (10/29) patients developed CRT within 60~&lt;120 days. Patients diagnosed with CRT received anticoagulant therapy for 3 months. Within three months, the thrombus regression rate reached 100.0% (29/29). Univariate analysis showed that whether to receive prophylactic anticoagulation, whether hemoglobin is normal, patients whether to experience previous endocrine therapy, different Age group and chemotherapy regimens were actors for thrombosis, P&lt;0.05 respectively. Multivariate analysis indicated that age and whether to receive prophylactic anticoagulation were independent factors for thrombosis ( P=0.019, P=0.006, respectively). Patients diagnosed with CRT received deep vein cannulation while anticoagulation therapy was administered, with smooth infusion. They all completed antitumor therapy as planned, and no abnormalities such as new thrombosis and pulmonary embolism were found. Conclusions: The prophylactic anticoagulation regimen with Rivaroxaban can reduce the incidence of CRT in breast cancer, showing good efficacy and safety. Therefore, medical staff should carry out early prevention, early detection and early treatment for CRT to improve the living quality of patients. Clinical trial information: ChiCTR2000031649.
Prediction Models for Individualized Treatment Effects of Oxygen Targets—Reply
Authors: Kevin G. Buell, Matthew W. Semler, Matthew M. Churpek
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
The Double-Edged Sword of Extremely High Prices for Gene Therapies in Sickle Cell Disease
Authors: Edward R. Scheffer Cliff, Frazer A. Tessema
Journal: JAMA (2024)

This Viewpoint discusses the high cost of new gene therapies for sickle cell disease, the challenges these costs pose for health care access, and new policy approaches to ensure fair reimbursement for payers and manufacturers without further increasing health care costs or barriers to access for underserved populations.
Varying selection pressure for a Na+ sensing site in epithelial Na+ channel subunits reflect divergent roles in Na+ homeostasis
Authors: Xue-Ping Wang, Priyanka Srinivasan, Mustapha El Hamdaoui, Brandon M Blobner, Rafael Grytz, Ossama B Kashlan
Journal: Molecular Biology and Evolution (2024)

The epithelial Na+ channel (ENaC) emerged early in vertebrates and has played a role in Na+ and fluid homeostasis throughout vertebrate evolution. We previously showed that proteolytic activation of the channel evolved at the water-to-land transition of vertebrates. Sensitivity to extracellular Na+, known as Na+ self-inhibition, reduces ENaC function when Na+ concentrations are high and is a distinctive feature of the channel. A fourth ENaC subunit, δ, emerged in jawed fishes from an α subunit gene duplication. Here, we analyzed 849 α and δ subunit sequences and found that a key Asp in a postulated Na+ binding site was nearly always present in the α subunit, but frequently lost in the δ subunit (e.g. human). Analysis of site evolution and codon substitution rates provide evidence that the ancestral α subunit had the site and that purifying selection for the site relaxed in the δ subunit after its divergence from the α subunit, coinciding with a loss of δ subunit expression in renal tissues. We also show that the proposed Na+ binding site in the α subunit is a bona fide site by conferring novel function to channels comprising human δ subunits. Together, our findings provide evidence that ENaC Na+ self-inhibition improves fitness through its role in Na+ homeostasis in vertebrates.
Pooled analysis by best confirmed response to trastuzumab deruxtecan (T-DXd) in patients (pts) with HER2+ metastatic breast cancer (mBC) from DESTINY-Breast-01, -02, and -03.
Authors: Cristina Saura, Javier Cortés, Shanu Modi, Sung-Bae Kim, Erika P. Hamilton, Sara A. Hurvitz, Ian E. Krop, Giuseppe Curigliano, Hiroji Iwata, Seock-Ah Im, Pia Maarit Herbolsheimer, Maha Karnoub, Dhiraj Gambhire, Anton Egorov, Fabrice Andre
Journal: Journal of Clinical Oncology (2024)

1023 Background: DESTINY-Breast (DB)-01, -02, and -03 evaluated T-DXd in pts with HER2+ mBC who received ≥1 prior line of therapy. These studies showed confirmed objective response rates by independent central review (ICR; blinded for DB-02 and -03) of 62%, 70%, and 79% and complete response (CR) rates of 7%, 14%, and 21%, respectively, with T-DXd. We report a pooled analysis according to pts’ best confirmed response in DB-01, -02, or -03. Methods: Endpoints included best confirmed response per (blinded) ICR ([B]ICR) based on RECIST v1.1, duration of response (DoR), progression-free survival (PFS) by (B)ICR, overall survival (OS), and safety. Results: The median (range) duration of T-DXd treatment for pts with a CR, partial response (PR), or stable disease (SD)/progressive disease (PD) was 27.4 (4.5-45.1) mo, 14.0 (2.1-39.3) mo, or 6.2 (0.7-40.1) mo, respectively. Of 834 evaluable pts assigned to T-DXd in DB-01, -02, or -03, 125 (15.0%) had a CR, 477 (57.2%) had a PR, and 232 (27.8%) had SD/PD. Pts with CR had a median of 2 prior regimens (range, 1-11) in the metastatic setting, whereas pts with PR or SD/PD had a median of 3 prior regimens. As shown in the Table, pts with CR had more favorable PFS and OS outcomes vs pts with PR or SD/PD. The proportion of pts with drug-related, serious treatment-emergent adverse events (TEAEs) was numerically lower in pts with CR (8.0%) than those with PR (12.4%) or SD/PD (15.5%). Pts with CR also had numerically lower rates of drug-related TEAEs associated with T-DXd discontinuation (14.4% vs 17.8% or 16.8%) and adjudicated drug-related interstitial lung disease (ILD)/pneumonitis (8.8% [0 fatal] vs 15.1% [2 fatal] or 11.6% [5 fatal]) and longer median time to first ILD onset (461 days vs 211 or 125 days) vs pts with PR or SD/PD. Conclusions: Pts treated with T-DXd benefited from durable responses resulting in prolonged PFS and OS, especially those with a CR. Despite longer treatment duration in responders, safety remained generally manageable and did not result in a higher percentage of pts with TEAEs over time. These results further support the use of T-DXd across broad pt groups with HER2+ mBC. Clinical trial information: NCT03248492 , NCT03523585 , NCT03529110 . [Table: see text]
A Multigenerational Model of Environmental Risk for Black, Indigenous, and People of Color (BIPOC) Children and Families
Authors: Janean E. Dilworth-Bart, Thea Sankari, Colleen F. Moore
Journal: Environmental Health Perspectives (2024)

In recent years, public discourse has increasingly brought institutional and structural racism to the foreground of discussion on the well-being of BIPOC (Black, Indigenous, and People of Color) communities. Environmental toxicity in combination with the social triggers of institutional and structural racism are among the factors that shape the short- and long-term health of BIPOC Americans across multiple lifespans.
Improving patient understanding of GEP test results (IMPARTER4): An RCT.
Authors: Lesley Fallowfield, Ivonne Solis-Trapala, Rachel Starkings, Lucy Matthews, Shirley May, Valerie A Jenkins
Journal: Journal of Clinical Oncology (2024)

527 Background: We developed two 8 min films to aid patients’ understanding about gene expression profiling (GEP) tests (Oncotype DX or Prosigna) in breast cancer. A previous study of 120 women without breast cancer demonstrated significantly better knowledge after film viewing compared to that after reading written materials (1). We present results of an RCT testing the films’ utility when given in clinics to women with early HR+ breast cancer for whom the benefit of chemotherapy was uncertain. Methods: Standard information policies about GEP testing differ, some clinics may provide patients with leaflets, others only verbal information. Patients who had consented to a GEP test were invited to join IMPARTER4. At baseline they completed anxiety trait/state and intolerance of uncertainty (IoU) questionnaires and were then randomized to Gp A (hospitals’ standard information alone) or Gp B (standard information plus the relevant GEP patient film). Prior to learning their risk of recurrence scores, researchers interviewed patients and probed their understanding and knowledge about GEP testing together with the role risk scores had in helping determine management options (hormone therapy plus or minus chemotherapy). Following test result discussions with oncologists, patients completed two further questionnaires measuring anxiety and decisional conflict. Treating physicians all completed IoU questionnaires once at baseline, Satisfaction with their clinical interviews conducted with patients about risk scores and management decisions was measured using a study specific questionnaire. Results: To date 225/230 patients from 18 UK hospitals (Gp A (standard information alone) n=103; Gp B (standard plus information film) n=122) were seen by 79 physicians. Socio-demographics, anxiety trait/state and IoU did not differ between groups. Prior to the results discussion, written information was given to 128/225 (56.9%), (66 in Gp A, and 62 in Gp B). Linear regression analyses (adjusted for age and education) showed that mean knowledge scores were higher in those receiving standard information plus the film (Gp B), (2.5 points (95% C.I:1.7-3.4) p&lt;0.001). There was a trend for longer consultations in those patients having standard information alone (Gp A) (12.6% v 8.2%), who also asked more difficult questions (9.7% v 2.5%). Conclusions: Patient information films significantly improved knowledge about GEP tests and recurrence risk results compared to standard verbal and written information alone. Furthermore, the films appeared to enable shorter, more informed discussions between patients and their oncologists about the addition of chemotherapy to hormone therapy alone. Versions in Spanish, Italian, French, Urdu, Hindi, Gujarati, Punjabi, and Bengali are freely available. 1. Fallowfield et al, Br Ca Res &amp; Tmt. 2022. Clinical trial information: 28497350.
BCAA-producing Clostridium symbiosum promotes colorectal tumorigenesis through the modulation of host cholesterol metabolism
Authors: Yi-Meng Ren, Zi-Yan Zhuang, Yuan-Hong Xie, Peng-Jie Yang, Tian-Xue Xia, Yi-Le Xie, Zhu-Hui Liu, Zi-Ran Kang, Xiao-Xu Leng, Shi-Yuan Lu, Lu Zhang, Jin-Xian Chen, Jia Xu, En-Hao Zhao, Zheng Wang, Ming Wang, Yun Cui, Juan Tan, Qiang Liu, Wei-Hong Jiang, Hua Xiong, Jie Hong, Ying-Xuan Chen, Hao-Yan Chen, Jing-Yuan Fang
Journal: Cell Host & Microbe (2024)
Safety of Direct Current Cardioversion Without Routine Transesophageal Echocardiography in Patients With Cardiac Amyloidosis
Authors: Osnat Itzhaki Ben Zadok, Sarah A.M. Cuddy, Hannah K. Gaggin, Olivier F. Clerc, Shilpa Vijayakumar, Sharmila Dorbala, Rodney H. Falk
Journal: Journal of the American College of Cardiology (2024)
Untethered Microgrippers for Biopsy in the Upper Urinary Tract
Authors: Wangqu Liu, Ridwan Alam, Si Young Choi, Yan Wan, Ruili Zhang, Ezra Baraban, Andres Matoso, Brian R. Matlaga, Jared S. Winoker, David H. Gracias
Journal: Advanced Healthcare Materials (2024)

Untethered microrobots offer the possibility to perform medical interventions in anatomically complex and small regions in the body. Presently, it is necessary to access the upper urinary tract to diagnose and treat Upper Tract Urothelial Carcinoma (UTUC). Diagnostic and treatment challenges include ensuring adequate tissue sampling, accurately grading the disease, achieving completeness in endoscopic treatment, and consistently delivering medications to targeted sites. This work introduces microgrippers (µ-grippers) that are autonomously triggered by physiological temperature for biopsy in the upper urinary tract. The experiments demonstrated that µ-grippers can be deployed using standard ureteral catheters and maneuvered using an external magnetic field. The μ-grippers successfully biopsied tissue samples from ex vivo pig ureters, indicating that the thin-film bilayer springs' autonomous, physiologically triggered actuation exerts enough force to retrieve urinary tract tissue. The quality of these biopsy samples is sufficient for histopathological examination, including hematoxylin and eosin (H&E) and GATA3 immunohistochemical staining. Beyond biopsy applications, the µ-grippers' small size, wafer-scale fabrication, and multifunctionality suggest their potential for statistical sampling in the urinary tract. Experimental data and clinical reports underscore this potential through statistical simulations that compare the efficacy of µ-grippers with conventional tools, such as ureteroscopic forceps and baskets.
Early Childhood Screen Use Contexts and Cognitive and Psychosocial Outcomes
Authors: Sumudu Mallawaarachchi, Jade Burley, Myrto Mavilidi, Steven J. Howard, Leon Straker, Lisa Kervin, Sally Staton, Nicole Hayes, Amanda Machell, Marina Torjinski, Brodie Brady, George Thomas, Sharon Horwood, Sonia L. J. White, Juliana Zabatiero, Clara Rivera, Dylan Cliff
Journal: JAMA Pediatrics (2024)

Importance The multifaceted nature of screen use has been largely overlooked in favor of a simplistic unidimensional measure of overall screen time when evaluating the benefits and risks of screen use to early childhood development. Objective To conduct a systematic review and meta-analysis to examine associations of screen use contexts in early childhood with cognitive and psychosocial outcomes. Data Sources PsycINFO, Embase, MEDLINE Ovid, ProQuest, CINAHL, Web of Science, and Scopus were searched from inception to December 31, 2023. Study Selection A total of 7441 studies were initially identified. Studies were included if they examined associations between a contextual factor of screen use among children aged 0 to 5.99 years and cognitive or psychosocial development. Observational, experimental, and randomized clinical trial study designs were included. Data Extraction and Synthesis All studies were independently screened in duplicate following PRISMA guidelines. Effect sizes of associations ( r ) from observational studies were pooled using random-effects 3-level meta-analyses. The remaining study designs were narratively synthesized. Main Outcomes and Measures Screen use contexts included content (child directed and age inappropriate), type (program viewing and game or app use), co-use (or solo use), background television, caregiver screen use during child routines, and purpose. Outcomes were cognitive (executive functioning, language, and academic skills) or psychosocial (internalizing and externalizing behavior problems and socioemotional competence). Results Overall, 100 studies (176 742 participants) were included, and of these, 64 observational studies (pooled sample sizes ranging from 711 to 69 232) were included in meta-analyses. Program viewing (n = 14; k = 48; r , −0.16; 95% CI, −0.24 to −0.08) and background television (n = 8; k = 18; r , −0.10; 95% CI, −0.18 to −0.02) were negatively associated with cognitive outcomes, while program viewing (n = 6; k = 31; r , −0.04; 95% CI, −0.07 to −0.01), age-inappropriate content (n = 9; k = 36; r , −0.11; 95% CI, −0.17 to −0.04), and caregiver screen use during routines (n = 6; k = 14; r , −0.11; 95% CI, −0.20 to −0.03) were negatively associated with psychosocial outcomes. Co-use was positively associated with cognitive outcomes (n = 8; k = 28; r , 0.14; 95% CI, 0.03 to 0.25). Conclusions and Relevance Findings show small to moderate effect sizes that highlight the need to consider screen use contexts when making recommendations for families, clinicians, and educators beyond screen time limits; including encouraging intentional and productive screen use, age-appropriate content, and co-use with caregivers.
Variation in the Spectrum of New Mutations among Inbred Strains of Mice
Authors: Eugenio López-Cortegano, Jobran Chebib, Anika Jonas, Anastasia Vock, Sven Künzel, Diethard Tautz, Peter D Keightley
Journal: Molecular Biology and Evolution (2024)

The mouse serves as a mammalian model for understanding the nature of variation from new mutations, a question that has both evolutionary and medical significance. Previous studies suggest that the rate of single-nucleotide mutations (SNMs) in mice is ∼50% of that in humans. However, information largely comes from studies involving the C57BL/6 strain, and there is little information from other mouse strains. Here, we study the mutations that accumulated in 59 mouse lines derived from four inbred strains that are commonly used in genetics and clinical research (BALB/cAnNRj, C57BL/6JRj, C3H/HeNRj, and FVB/NRj), maintained for eight to nine generations by brother-sister mating. By analyzing Illumina whole-genome sequencing data, we estimate that the average rate of new SNMs in mice is ∼μ = 6.7 × 10-9. However, there is substantial variation in the spectrum of SNMs among strains, so the burden from new mutations also varies among strains. For example, the FVB strain has a spectrum that is markedly skewed toward C→A transversions and is likely to experience a higher deleterious load than other strains, due to an increased frequency of nonsense mutations in glutamic acid codons. Finally, we observe substantial variation in the rate of new SNMs among DNA sequence contexts, CpG sites, and their adjacent nucleotides playing an important role.
The Role of Social Workers in Hypertension Care for Black Adults—Reply
Authors: Monika M. Safford, Andrea L. Cherrington
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
Invasion and amplification of endogenous retroviruses in <i>Dasyuridae</i> marsupial genomes
Authors: Emma F Harding, Lewis K Mercer, Grace J H Yan, Paul D Waters, Peter A White
Journal: Molecular Biology and Evolution (2024)

Abstract Retroviruses are an ancient viral family that have globally coevolved with vertebrates and impacted their evolution. In Australia, a continent that has been geographically isolated for millions of years, little is known about retroviruses in wildlife, despite the devastating impacts of a retrovirus on endangered koala populations. We therefore sought to identify and characterize Australian retroviruses through reconstruction of endogenous retroviruses from marsupial genomes, in particular the Tasmanian devil due to its high cancer incidence. We screened 19 marsupial genomes and identified over 80,000 endogenous retrovirus fragments which we classified into eight retrovirus clades. The retroviruses were similar to either Betaretrovirus (5/8) or Gammaretrovirus (3/8) retroviruses, but formed distinct phylogenetic clades compared to extant retroviruses. One of the clades (MEBrv 3) lost an envelope but retained retrotranspositional activity, subsequently amplifying throughout all Dasyuridae genomes. Overall, we provide insights into Australian retrovirus evolution and identify a highly active endogenous retrovirus within Dasyuridae genomes.