tbuckley/cabot-search huggingface dataset:
Conserved immuno‐collagenic subtypes predict response to immune checkpoint blockade
Authors: Jie Mei, Yun Cai, Rui Xu, Qing Li, Jiahui Chu, Zhiwen Luo, Yaying Sun, Yuxin Shi, Junying Xu, Di Li, Shuai Liang, Ying Jiang, Jiayu Liu, Zhiwen Qian, Jiaofeng Zhou, Mengyun Wan, Yunlong Yang, Yichao Zhu, Yan Zhang, Yongmei Yin
Journal: Cancer Communications (2024)

Immune checkpoint blockade (ICB) has revolutionized the treatment of various cancer types. Despite significant preclinical advancements in understanding mechanisms, identifying the molecular basis and predictive biomarkers for clinical ICB responses remains challenging. Recent evidence, both preclinical and clinical, underscores the pivotal role of the extracellular matrix (ECM) in modulating immune cell infiltration and behaviors. This study aimed to create an innovative classifier that leverages ECM characteristics to enhance the effectiveness of ICB therapy.
The ClC-1 chloride channel inhibitor NMD670 improves skeletal muscle function in rat models and patients with myasthenia gravis
Authors: Martin Skov, Titia Q. Ruijs, Thomas S. Grønnebæk, Marianne Skals, Anders Riisager, Jeppe Blichfeldt Winther, Kamilla Løhde Tordrup Dybdahl, Anders Findsen, Jeanette J. Morgen, Nete Huus, Martin Broch-Lips, Ole B. Nielsen, Catherine M.K.E. de Cuba, Jules A.A.C. Heuberger, Marieke L. de Kam, Martijn Tannemaat, Jan J. G. M. Verschuuren, Lars J. S. Knutsen, Nicholas M. Kelly, Klaus G. Jensen, William D. Arnold, Arthur H. Burghes, Claus Olesen, Jane Bold, Thomas K. Petersen, Jorge A. Quiroz, John Hutchison, Eva R. Chin, Geert J. Groeneveld, Thomas H. Pedersen
Journal: Science Translational Medicine (2024)

Myasthenia gravis (MG) is a neuromuscular disease that results in compromised transmission of electrical signals at the neuromuscular junction (NMJ) from motor neurons to skeletal muscle fibers. As a result, patients with MG have reduced skeletal muscle function and present with symptoms of severe muscle weakness and fatigue. ClC-1 is a skeletal muscle specific chloride (Cl − ) ion channel that plays important roles in regulating neuromuscular transmission and muscle fiber excitability during intense exercise. Here, we show that partial inhibition of ClC-1 with an orally bioavailable small molecule (NMD670) can restore muscle function in rat models of MG and in patients with MG. In severely affected MG rats, ClC-1 inhibition enhanced neuromuscular transmission, restored muscle function, and improved mobility after both single and prolonged administrations of NMD670. On this basis, NMD670 was progressed through nonclinical safety pharmacology and toxicology studies, leading to approval for testing in clinical studies. After successfully completing phase 1 single ascending dose in healthy volunteers, NMD670 was tested in patients with MG in a randomized, placebo-controlled, single-dose, three-way crossover clinical trial. The clinical trial evaluated safety, pharmacokinetics, and pharmacodynamics of NMD670 in 12 patients with mild MG. NMD670 had a favorable safety profile and led to clinically relevant improvements in the quantitative myasthenia gravis (QMG) total score. This translational study spanning from single muscle fiber recordings to patients provides proof of mechanism for ClC-1 inhibition as a potential therapeutic approach in MG and supports further development of NMD670.
An anti–TNF–glucocorticoid receptor modulator antibody-drug conjugate is efficacious against immune-mediated inflammatory diseases
Authors: Michael J. McPherson, Adrian D. Hobson, Axel Hernandez, Christopher C. Marvin, Wendy Waegell, Christian Goess, Jason Z. Oh, Dan Shi, Martin E. Hayes, Lu Wang, Lu Wang, Diana Schmidt, Zhi Wang, Victoria Pitney, Kimberley McCarthy, Ying Jia, Ce Wang, Bit Na Kang, Shaughn Bryant, Suzanne Mathieu, Melanie Ruzek, Julie Parmentier, Ronilda R. D’Cunha, Yinuo Pang, Lucy Phillips, Nathan J. Brown, Jianwen Xu, Candace Graff, Yu Tian, Kenton L. Longenecker, Wei Qiu, Haizhong Zhu, Wei Liu, Pingping Zheng, Yingtao Bi, Robert Stoffel
Journal: Science Translational Medicine (2024)

Glucocorticoids (GCs) are efficacious drugs used for treating many inflammatory diseases, but the dose and duration of administration are limited because of severe side effects. We therefore sought to identify an approach to selectively target GCs to inflamed tissue. Previous work identified that anti–tumor necrosis factor (TNF) antibodies that bind to transmembrane TNF undergo internalization; therefore, an anti-TNF antibody-drug conjugate (ADC) would be mechanistically similar, where lysosomal catabolism could release a GC receptor modulator (GRM) payload to dampen immune cell activity. Consequently, we have generated an anti–TNF-GRM ADC with the aim of inhibiting pro-inflammatory cytokine production from stimulated human immune cells. In an acute mouse model of contact hypersensitivity, a murine surrogate anti–TNF-GRM ADC inhibited inflammatory responses with minimal effect on systemic GC biomarkers. In addition, in a mouse model of collagen-induced arthritis, single-dose administration of the ADC, delivered at disease onset, was able to completely inhibit arthritis for greater than 30 days, whereas an anti-TNF monoclonal antibody only partially inhibited disease. ADC treatment at the peak of disease was also able to attenuate the arthritic phenotype. Clinical data for a human anti–TNF-GRM ADC (ABBV-3373) from a single ascending dose phase 1 study in healthy volunteers demonstrated antibody-like pharmacokinetic profiles and a lack of impact on serum cortisol concentrations at predicted therapeutic doses. These data suggest that an anti–TNF-GRM ADC may provide improved efficacy beyond anti-TNF alone in immune mediated diseases while minimizing systemic side effects associated with standard GC treatment.
EGFR amplification and EGFRvIII predict and participate in TAT-Cx43266–283 antitumor response in preclinical glioblastoma models
Authors: Andrea Álvarez-Vázquez, Laura San-Segundo, Pilar Cerveró-García, Raquel Flores-Hernández, Claudia Ollauri-Ibáñez, Berta Segura-Collar, Christopher G Hubert, Gillian Morrison, Steven M Pollard, Justin D Lathia, Pilar Sánchez-Gómez, Arantxa Tabernero
Journal: Neuro-Oncology (2024)

Abstract Background Glioblastoma (GBM) commonly displays epidermal growth factor receptor (EGFR) alterations (mainly amplification and EGFRvIII) and TAT-Cx43266–283 is a Src-inhibitory peptide with antitumor properties in preclinical GBM models. Given the link between EGFR and Src, the aim of this study was to explore the role of EGFR in the antitumor effects of TAT-Cx43266–283. Methods The effect of TAT-Cx43266–283, temozolomide (TMZ), and erlotinib (EGFR inhibitor) was studied in patient-derived GBM stem cells (GSCs) and murine neural stem cells (NSCs) with and without EGFR alterations, in vitro and in vivo. EGFR alterations were analyzed by western blot and fluorescence in situ hybridization in these cells, and compared with Src activity and survival in GBM samples from The Cancer Genome Atlas. Results The effect of TAT-Cx43266–283 correlated with EGFR alterations in a set of patient-derived GSCs and was stronger than that exerted by TMZ and erlotinib. In fact, TAT-Cx43266-283 only affected NSCs with EGFR alterations, but not healthy NSCs. EGFR alterations correlated with Src activity and poor survival in GBM patients. Finally, tumors generated from NSCs with EGFR alterations showed a decrease in growth, invasiveness, and vascularization after treatment with TAT-Cx43266–283, which enhanced the survival of immunocompetent mice. Conclusions Clinically relevant EGFR alterations are predictors of TAT-Cx43266–283 response and part of its mechanism of action, even in TMZ- and erlotinib-resistant GSCs. TAT-Cx43266–283 targets NSCs with GBM-driver mutations, including EGFR alterations, in an immunocompetent GBM model in vivo, suggesting a promising effect on GBM recurrence. Together, this study represents an important step toward the clinical application of TAT-Cx43266–283.
Optimizing antithrombotic therapy in patients with coexisting cardiovascular and gastrointestinal disease
Authors: Azita H. Talasaz, Parham Sadeghipour, Luis Ortega-Paz, Hessam Kakavand, Maryam Aghakouchakzadeh, Craig Beavers, John Fanikos, John W. Eikelboom, Deborah M. Siegal, Manuel Monreal, David Jimenez, Muthiah Vaduganathan, Lana A. Castellucci, Adam Cuker, Geoffrey D. Barnes, Jean M. Connors, Eric A. Secemsky, Benjamin W. Van Tassell, Raffaele De Caterina, Jacob E. Kurlander, Ali Aminian, Gregory Piazza, Samuel Z. Goldhaber, Lisa Moores, Saskia Middeldorp, Ajay J. Kirtane, Mitchell S. V. Elkind, Dominick J. Angiolillo, Stavros Konstantinides, Gregory Y. H. Lip, Gregg W. Stone, Mary Cushman, Harlan M. Krumholz, Roxana Mehran, Deepak L. Bhatt, Behnood Bikdeli
Journal: Nature Reviews Cardiology (2024)
Primary biliary cholangitis drug evaluation and regulatory approval: Where do we go from here?
Authors: David E.J. Jones, Ulrich Beuers, Alan Bonder, Marco Carbone, Emma Culver, Jessica Dyson, Robert G. Gish, Bettina E. Hansen, Gideon Hirschfield, Rebecca Jones, Kris Kowdley, Andreas E. Kremer, Keith Lindor, Marlyn Mayo, George Mells, James Neuberger, Martin Prince, Mark Swain, Atsushi Tanaka, Douglas Thorburn, Michael Trauner, Palak Trivedi, Martin Weltman, Andrew Yeoman, Cynthia Levy
Journal: Hepatology (2024)

Primary biliary cholangitis (PBC) is a chronic cholestatic liver disease. The management landscape was transformed 20 years ago with the advent of ursodeoxycholic acid. Up to 40% of patients do not, however, respond adequately to ursodeoxycholic acid and therefore still remain at risk of disease progression to cirrhosis. The introduction of obeticholic acid as a second-line therapy for patients failing ursodeoxycholic acid has improved outcomes for patients with PBC. There remains, however, a need for better treatment for patients at higher risk. The greatest threat facing our efforts to improve treatment in PBC is, paradoxically, the regulatory approval model providing conditional marketing authorization for new drugs based on biochemical markers on the condition that long-term, randomized placebo-controlled outcome trials are performed to confirm efficacy. As demonstrated by the COBALT confirmatory study with obeticholic acid, it is difficult to retain patients in the required follow-on confirmatory placebo-controlled PBC outcome trials when a licensed drug is commercially available. New PBC therapies in development, such as the peroxisome proliferator–activated receptor agonists, face even greater challenges in demonstrating outcome benefit through randomized placebo-controlled studies once following conditional marketing authorization, as there will be even more treatment options available. A recently published EMA Reflection Paper provides some guidance on the regulatory pathway to full approval but fails to recognize the importance of real-world data in providing evidence of outcome benefit in rare diseases. Here we explore the impact of the EMA reflection paper on PBC therapy and offer pragmatic solutions for generating evidence of long-term outcomes through real-world data collection.
Prenatal Household Air Pollution Exposure and Childhood Blood Pressure in Rural Ghana
Authors: Misbath Daouda, Seyram Kaali, Emma Spring, Mohammed N. Mujtaba, Darby Jack, Rebecca Kyerewaa Dwommoh Prah, Elena Colicino, Theresa Tawiah, Chris Gennings, Musah Osei, Teresa Janevic, Steven N. Chillrud, Oscar Agyei, Carlos F. Gould, Alison G. Lee, Kwaku Poku Asante
Journal: Environmental Health Perspectives (2024)

The association between prenatal household air pollution (HAP) exposure and childhood blood pressure (BP) is unknown.
Prevalence of lung cysts in adolescents and adults with a germline<i>DICER1</i>pathogenic/likely pathogenic variant: a report from the National Institutes of Health and International Pleuropulmonary Blastoma/<i>DICER1</i>Registry
Authors: Alexander T Nelson, Lauren M Vasta, Dave Watson, Jung Kim, Anne K Harris, Ana F Best, Laura A Harney, Ann G Carr, Nicole Frederickson, Louis P Dehner, Christian P Kratz, Kelly N Hagedorn, William A Mize, Alexander Ling, Yoav H Messinger, D Ashley Hill, Kris Ann P Schultz, Douglas R Stewart
Journal: Thorax (2024)

Background Pleuropulmonary blastoma (PPB), the hallmark tumour associated with DICER1 -related tumour predisposition, is characterised by an age-related progression from a cystic lesion (type I) to a high-grade sarcoma with mixed cystic and solid features (type II) or purely solid lesion (type III). Not all cystic PPBs progress; type Ir (regressed), hypothesised to represent regressed or non-progressed type I PPB, is an air-filled, cystic lesion lacking a primitive sarcomatous component. This study aims to evaluate the prevalence of non-progressed lung cysts detected by CT scan in adolescents and adults with germline DICER1 pathogenic/likely pathogenic (P/LP) variants. Methods Individuals were enrolled in the National Cancer Institute Natural History of DICER1 Syndrome study, the International PPB/ DICER1 Registry and/or the International Ovarian and Testicular Stromal Tumor Registry. Individuals with a germline DICER1 P/LP variant with first chest CT at 12 years of age or older were selected for this analysis. Results In the combined databases, 110 individuals with a germline DICER1 P/LP variant who underwent first chest CT at or after the age of 12 were identified. Cystic lung lesions were identified in 38% (42/110) with a total of 72 cystic lesions detected. No demographic differences were noted between those with lung cysts and those without lung cysts. Five cysts were resected with four centrally reviewed as type Ir PPB. Conclusion Lung cysts are common in adolescents and adults with germline DICER1 variation. Further study is needed to understand the mechanism of non-progression or regression of lung cysts in childhood to guide judicious intervention.
Epidemiology of musculoskeletal injury in professional and amateur golfers: a systematic review and meta-analysis
Authors: Thomas R Williamson, Robert S Kay, Patrick G Robinson, Andrew D Murray, Nicholas D Clement
Journal: British Journal of Sports Medicine (2024)

Objective To determine the prevalence and incidence of musculoskeletal injury in amateur and professional golfers, and to identify common injury sites and factors associated with increased injury frequency. Design Systematic epidemiological review and meta-analysis. Data sources PubMed (Medline), Embase, the Cochrane Library and SPORTDiscus were searched in September 2023. Eligibility criteria Studies published in the English language reporting the incidence or prevalence of musculoskeletal injuries in golfers at all anatomical sites. Results 20 studies (9221 golfers, 71.9% male, 28.1% female) were included, with mean age 46.8 years. Lifetime injury prevalence was significantly greater in professional golfers (73.5% (95% CI: 47.3% to 93.0%)) than amateur golfers (56.6% (95% CI: 47.4% to 65.5%); relative risk (RR)=1.50, p&lt;0.001). Professional golfers had a significantly greater lifetime prevalence of hand and wrist (RR=3.33, p&lt;0.001) and lower back injury (RR=3.05, p&lt;0.001). Soft tissue injuries were most common, and diagnoses were typically non-specific. Injury frequency was not associated with age or sex. Two studies reported a greater injury risk in amateur golfers playing more than three and four rounds per week. Conclusion Over half of golfers are at risk of sustaining a musculoskeletal injury during their lifetime. Risks and patterns of injury differ between professional and amateur golfers, with professionals significantly more likely to develop lower back, and hand and wrist injuries. A recent international consensus statement on the reporting of injury and illness in golf should aid consistency in future research assessing the epidemiology of specific diagnoses, informing golf injury prevention and management strategies. PROSPERO registration number CRD42023408738.
Human mesenchymal stromal cells inhibit<i>Mycobacterium avium</i>replication in clinically relevant models of lung infection
Authors: Timothy D Shaw, Anna D Krasnodembskaya, Gunnar N Schroeder, Declan F Doherty, Johnatas Dutra Silva, Shikha M Tandel, Yue Su, David Butler, Rebecca J Ingram, Cecilia M O'Kane
Journal: Thorax (2024)

Novel therapeutic strategies are urgently needed for
Modifier 22—Is It All Just a Catch-22?
Authors: Ali B. Abbasi, Elizabeth C. Wick
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
Single-Cell RNA Sequencing Identifies Response of Renal Lymphatic Endothelial Cells to Acute Kidney Injury
Authors: Heidi A. Creed, Saranya Kannan, Brittany L. Tate, David Godefroy, Priyanka Banerjee, Brett M. Mitchell, Ebba Brakenhielm, Sanjukta Chakraborty, Joseph M. Rutkowski
Journal: Journal of the American Society of Nephrology (2024)

The renal lymphatic vasculature and the lymphatic endothelial cells that make up this network play important immunomodulatory roles during inflammation. How lymphatics respond to AKI may affect AKI outcomes. The authors used single-cell RNA sequencing to characterize mouse renal lymphatic endothelial cells in quiescent and cisplatin-injured kidneys. Lymphatic endothelial cell gene expression changes were confirmed in ischemia-reperfusion injury and in cultured lymphatic endothelial cells, validating renal lymphatic endothelial cells single-cell RNA sequencing data. This study is the first to describe renal lymphatic endothelial cell heterogeneity and uncovers molecular pathways demonstrating lymphatic endothelial cells regulate the local immune response to AKI. These findings provide insights into previously unidentified molecular pathways for lymphatic endothelial cells and roles that may serve as potential therapeutic targets in limiting the progression of AKI.
Racial Implicit Bias and Communication Among Physicians in a Simulated Environment
Authors: Cristina M. Gonzalez, Tavinder K. Ark, Marla R. Fisher, Paul R. Marantz, Diana J. Burgess, Felise Milan, Malika T. Samuel, Monica L. Lypson, Carlos J. Rodriguez, Adina L. Kalet
Journal: JAMA Network Open (2024)

Importance Racial implicit bias can contribute to health disparities through its negative influence on physician communication with Black patients. Interventions for physicians to address racial implicit bias in their clinical encounters are limited by a lack of high-fidelity (realistic) simulations to provide opportunities for skill development and practice. Objective To describe the development and initial evaluation of a high-fidelity simulation of conditions under which physicians might be influenced by implicit racial bias. Design, Setting, and Participants This cross-sectional study, performed on an online platform from March 1 to September 30, 2022, recruited a convenience sample of physician volunteers to pilot an educational simulation. Exposures In the simulation exercise, physicians saw a 52-year-old male standardized patient (SP) (presenting as Black or White) seeking urgent care for epigastric pain, nausea, and vomiting. The case included cognitive stressors common to clinical environments, including clinical ambiguity, stress, time constraints, and interruptions. Physicians explained their diagnosis and treatment plan to the SP, wrote an assessment and management plan, completed surveys, and took the Race Implicit Association Test (IAT) and Race Medical Cooperativeness IAT. The SPs, blinded to the purpose of the study, assessed each physician’s communication using skills checklists and global rating scales. Main Outcomes and Measures Association between physicians’ IAT scores and SP race with SP ratings of communication skills. Results In 60 physicians (23 [38.3%] Asian, 4 [6.7%] Black, 23 [38.3%] White, and 10 [16.7%] other, including Latina/o/x, Middle Eastern, and multiracial; 31 [51.7%] female, 27 [45.0%] male, and 2 [3.3%] other), the interaction of physicians’ Race IAT score and SP race was significant for overall communication (mean [SD] β = −1.29 [0.41]), all subdomains of communication (mean [SD] β = −1.17 [0.52] to −1.43 [0.59]), and overall global ratings (mean [SD] β = −1.09 [0.39]). Black SPs rated physicians lower on communication skills for a given pro-White Race IAT score than White SPs; White SP ratings increased as physicians’ pro-White bias increased. Conclusions and Relevance In this cross-sectional study, a high-fidelity simulation calibrated with cognitive stressors common to clinical environments elicited the expected influence of racial implicit bias on physicians’ communication skills. The outlined process and preliminary results can inform the development and evaluation of interventions that seek to address racial implicit bias in clinical encounters and improve physician communication with Black patients.
Errors in Results, Table 2, Table 3, and Supplement 2
Journal: JAMA Network Open (2024)

Investigation titled "Unconditional Cash Transfers and Maternal Assessments of Children's Health, Nutrition, and Sleep: A Randomized Clinical Trial," 1 published September 29, 2023, the preregistration document stated that all linear analyses would be standardized to the control group; however, the analyses conducted for this paper were standardized to the full sample.The corrected article 1 includes changes in the second paragraph of the "Impacts on Health, Nutrition, Sleep, and Health Care Utilization" subsection in the Results section; Table 3; and Supplement 2. Text was also added to the Methods section to clarify the standardization process.Additionally, the mean (SD) birth weight reported should have read 7.11 (1.05) pounds, and the percentages for maternal report of child's diagnosis in Table 2 have been updated.This article has been corrected.
Baseline Antipsychotic Dose and Transition to Psychosis in Individuals at Clinical High Risk
Authors: Andrea Raballo, Michele Poletti, Antonio Preti
Journal: JAMA Psychiatry (2024)

Emerging meta-analytical evidence indicates that baseline exposure to antipsychotics is associated with an increased risk of transitioning to psychosis in individuals at clinical high-risk for psychosis (CHR-P) and that such effect is not a result of pretest risk enrichment. However, to maximize its translational utility for prognostic stratification in clinical practice, testing for the potential presence of a dose-response association is crucial.
Electrocardiographic Findings in Female Professional Basketball Athletes
Authors: Bradley S. Lander, Eamon Y. Duffy, Jessica A. Hennessey, Sonia Tolani, Nidhi Patel, Michael S. Bohnen, Jeffrey J. Hsu, Alfred Danielian, Ankit B. Shah, Marci Goolsby, Matthew W. Martinez, Dermot Phelan, David J. Engel
Journal: JAMA Cardiology (2024)

Previous studies of professional basketball athletes have characterized manifestations of athletic remodeling by echocardiography and electrocardiography (ECG) in males and echocardiography in females. There is a paucity of female, basketball-specific ECG data.