tbuckley/cabot-search huggingface dataset:
A combination of PD-L1-targeted IL-15 mRNA nanotherapy and ultrasound-targeted microbubble destruction for tumor immunotherapy
Authors: Xiaoxuan Wang, Fangxuan Li, Jialu Zhang, Lu Guo, Mengmeng Shang, Xiao Sun, Shan Xiao, Dandan Shi, Dong Meng, Yading Zhao, Chao Jiang, Jie Li
Journal: Journal of Controlled Release (2024)
Early changes in estimated glomerular filtration rate post‐initiation of empagliflozin in <scp>EMPEROR‐Preserved</scp>
Authors: Tripti Rastogi, João Pedro Ferreira, Javed Butler, Bettina Johanna Kraus, Michaela Mattheus, Martina Brueckmann, Gerasimos Filippatos, Christoph Wanner, Stuart J. Pocock, Milton Packer, Stefan D. Anker, Faiez Zannad
Journal: European Journal of Heart Failure (2024)
Cancer mortality in chrysotile miners and millers, Russian Federation: main results (Asbest Chrysotile Cohort-Study)
Authors: Joachim Schüz, Evgeny Kovalevskiy, Ann Olsson, Monika Moissonnier, Evgenia Ostroumova, Gilles Ferro, Eleonora Feletto, Sara J Schonfeld, Graham Byrnes, Iraklii Tskhomariia, Kurt Straif, Tatiana Morozova, Hans Kromhout, Igor Bukhtiyarov
Journal: JNCI Journal of the National Cancer Institute (2024)

Abstract Background We investigated mortality in workers of the world’s largest chrysotile mine and enrichment factories located in the town of Asbest, Russian Federation. Methods This historical cohort study included all workers employed for at least 1 year between 1975 and 2010 and follow-up until the end of 2015. Cumulative exposure to dust was estimated based on workers’ complete occupational history linked to dust measurements systematically collected from the 1950s. Exposure to chrysotile fibers was estimated using dust-to-fiber conversion factors. Relative risks (RRs) and 95% confidence intervals (CIs) were estimated as mortality rate ratios in Poisson regression models. Results A total of 30 445 (32% women) workers accumulated 721 312 person-years at risk and 11 110 (36%) died. Of the workers, 54% had more than 30 years since their first exposure. We found an exposure-response between cumulative dust and lung cancer mortality in men. No clear association with dust exposure but a modest increase in the highest category of fiber exposure was seen for lung cancer in women. Mesothelioma mortality was increased (RR = 7.64, 95% CI = 1.18 to 49.5, to at least 80 fibers per cm3 years and RR = 4.56, 95% CI = 0.94 to 22.1, to at least 150 mg/m3 years [dust]), based on 13 deaths. For colorectal and stomach cancer, there were inconsistent associations. No associations were seen for laryngeal or ovarian cancer. Conclusion In this large-scale epidemiological study in the world’s largest active asbestos mine, we confirmed an increased risk of mesothelioma with high fiber exposure and an increasing mortality for lung cancer in men with increasing dust exposure. Less clear-cut increased lung cancer mortality was seen in the women. Continued mortality follow-up is warranted.
cGAS Activation Accelerates the Progression of Autosomal Dominant Polycystic Kidney Disease
Authors: Miran Yoo, Jonathan C. Haydak, Evren U. Azeloglu, Kyung Lee, G. Luca Gusella
Journal: Journal of the American Society of Nephrology (2024)

The renal immune infiltrate observed in autosomal polycystic kidney disease contributes to the evolution of the disease. Elucidating the cellular mechanisms underlying the inflammatory response could help devise new therapeutic strategies. Here, we provide evidence for a mechanistic link between the deficiency polycystin-1 and mitochondrial homeostasis and the activation of the cyclic guanosine monophosphate-adenosine monophosphate synthase (cGAS)/stimulator of the interferon genes (STING) pathway. Our data identify cGAS as an important mediator of renal cystogenesis and suggest that its inhibition may be useful to slow down the disease progression.
Whose Responsibility Is It to Define Exceptions in Abortion Bans?
Authors: Carmel Shachar, Susannah Baruch, Louise P. King
Journal: JAMA (2024)

This Viewpoint evaluates Texas’ proposals to define the scope of the life exception for the state’s abortion ban and argues that these approaches do not allow physicians to follow the national standards of care, avoid criminal liability, or have sufficient notice of what the law permits.
Myocardial perfusion in cardiac amyloidosis
Authors: Liza Chacko, Tushar Kotecha, Adam Ioannou, Niket Patel, Ana Martinez‐Naharro, Yousuf Razvi, Rishi Patel, Paolo Massa, Lucia Venneri, James Brown, Aldostefano Porcari, Kristopher Knott, Charlotte Manisty, Daniel Knight, Tim Lockie, Roby Rakhit, Helen Lachmann, Ashutosh Wechelakar, Carol Whelan, Markella Ponticos, James Moon, Arantxa González, Janet Gilbertson, Mattia Riefolo, Ornella Leone, Hui Xue, Philip Hawkins, Peter Kellman, Julian Gillmore, Marianna Fontana
Journal: European Journal of Heart Failure (2024)

Cardiac involvement is the main driver of clinical outcomes in systemic amyloidosis and preliminary studies support the hypothesis that myocardial ischaemia contributes to cellular damage. The aims of this study were to assess the presence and mechanisms of myocardial ischaemia using cardiovascular magnetic resonance (CMR) with multiparametric mapping and histopathological assessment.
Multifunctional On‐Demand Removability Hydrogel Dressing Based on in Situ Formed AgNPs, Silk Microfibers and Hydrazide Hyaluronic Acid for Burn Wound Healing
Authors: Jueying Chen, Xin Zhao, Lipeng Qiao, Ying Huang, Yutong Yang, Dake Chu, Baolin Guo
Journal: Advanced Healthcare Materials (2024)

Abstract Elevated temperatures can deactivate tissues in the burn wound area, allowing pathogenic bacteria to multiply on the wound surface, ultimately leading to local or systemic infection. An ideal burn dressing should provide antibacterial properties and facilitate painless dressing changes. Silk microfibers coated with poly (2, 3, 4‐trihydroxybenzaldehyde) (referred to as mSF@PTHB) to in situ reduce AgNO 3 to silver nanoparticles (AgNPs) in a hydrazide hyaluronic acid‐based hydrogel are utilized. The findings indicate a more homogeneous distribution of the silver elements compared to directly doped AgNPs, which also conferred antioxidant and antibacterial properties to the hydrogel. Moreover, hydrogels containing pH‐responsive dynamic acylhydrazone bonds can undergo a gel‐sol transition in a weak acid environment, leading to the painless removal of adhesive hydrogel dressings. Notably, the on‐demand replaceable self‐healing antioxidant hydrogel dressing exhibits antibacterial effects and cytocompatibility in vitro, and the wound‐healing performance of the hydrogel is validated by treating a burn mouse model with full‐thickness skin defects. It is demonstrated that hydrogel dressings offer a viable therapeutic approach to prevent infection and facilitate the healing of burn wounds.
Role of Genetic Risk in the Association Between Screen Time and Child Development
Authors: Ippei Takahashi, Taku Obara, Shinichi Kuriyama
Journal: JAMA Pediatrics (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 Pediatrics 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 Pediatrics journal
SURGE: uncovering context-specific genetic-regulation of gene expression from single-cell RNA sequencing using latent-factor models
Authors: Benjamin J. Strober, Karl Tayeb, Joshua Popp, Guanghao Qi, M. Grace Gordon, Richard Perez, Chun Jimmie Ye, Alexis Battle
Journal: Genome biology (2024)

Abstract Genetic regulation of gene expression is a complex process, with genetic effects known to vary across cellular contexts such as cell types and environmental conditions. We developed SURGE, a method for unsupervised discovery of context-specific expression quantitative trait loci (eQTLs) from single-cell transcriptomic data. This allows discovery of the contexts or cell types modulating genetic regulation without prior knowledge. Applied to peripheral blood single-cell eQTL data, SURGE contexts capture continuous representations of distinct cell types and groupings of biologically related cell types. We demonstrate the disease-relevance of SURGE context-specific eQTLs using colocalization analysis and stratified LD-score regression.
PICALO: principal interaction component analysis for the identification of discrete technical, cell-type, and environmental factors that mediate eQTLs
Authors: Martijn Vochteloo, Patrick Deelen, Britt Vink, Ellen A. Tsai, Heiko Runz, Sergio Andreu-Sánchez, Jingyuan Fu, Alexandra Zhernakova, Harm-Jan Westra, Lude Franke
Journal: Genome biology (2024)

Abstract Expression quantitative trait loci (eQTL) offer insights into the regulatory mechanisms of trait-associated variants, but their effects often rely on contexts that are unknown or unmeasured. We introduce PICALO, a method for hidden variable inference of eQTL contexts. PICALO identifies and disentangles technical from biological context in heterogeneous blood and brain bulk eQTL datasets. These contexts are biologically informative and reproducible, outperforming cell counts or expression-based principal components. Furthermore, we show that RNA quality and cell type proportions interact with thousands of eQTLs. Knowledge of hidden eQTL contexts may aid in the inference of functional mechanisms underlying disease variants.
The Molecular Twin artificial-intelligence platform integrates multi-omic data to predict outcomes for pancreatic adenocarcinoma patients
Authors: Arsen Osipov, Ognjen Nikolic, Arkadiusz Gertych, Sarah Parker, Andrew Hendifar, Pranav Singh, Darya Filippova, Grant Dagliyan, Cristina R. Ferrone, Lei Zheng, Jason H. Moore, Warren Tourtellotte, Jennifer E. Van Eyk, Dan Theodorescu
Journal: Nature Cancer (2024)

Abstract Contemporary analyses focused on a limited number of clinical and molecular biomarkers have been unable to accurately predict clinical outcomes in pancreatic ductal adenocarcinoma. Here we describe a precision medicine platform known as the Molecular Twin consisting of advanced machine-learning models and use it to analyze a dataset of 6,363 clinical and multi-omic molecular features from patients with resected pancreatic ductal adenocarcinoma to accurately predict disease survival (DS). We show that a full multi-omic model predicts DS with the highest accuracy and that plasma protein is the top single-omic predictor of DS. A parsimonious model learning only 589 multi-omic features demonstrated similar predictive performance as the full multi-omic model. Our platform enables discovery of parsimonious biomarker panels and performance assessment of outcome prediction models learning from resource-intensive panels. This approach has considerable potential to impact clinical care and democratize precision cancer medicine worldwide.
Author Correction: Oxycodone withdrawal induces HDAC1/HDAC2-dependent transcriptional maladaptations in the reward pathway in a mouse model of peripheral nerve injury
Authors: Kerri D. Pryce, Randal A. Serafini, Aarthi Ramakrishnan, Andrew Nicolais, Ilinca M. Giosan, Claire Polizu, Angélica Torres-Berrío, Sreeya Vuppala, Hope Kronman, Anne Ruiz, Sevasti Gaspari, Catherine J. Peña, Farhana Sakloth, Vasiliki Mitsi, John van Duzer, Ralph Mazitschek, Matthew Jarpe, Li Shen, Eric J. Nestler, Venetia Zachariou
Journal: Nature Neuroscience (2024)
Nasopharyngeal carcinoma: current views on the tumor microenvironment's impact on drug resistance and clinical outcomes
Authors: Huai Liu, Ling Tang, Yanxian Li, Wenji Xie, Ling Zhang, Hailin Tang, Tengfei Xiao, Hongmin Yang, Wangning Gu, Hui Wang, Pan Chen
Journal: Molecular Cancer (2024)

Abstract The incidence of nasopharyngeal carcinoma (NPC) exhibits significant variations across different ethnic groups and geographical regions, with Southeast Asia and North Africa being endemic areas. Of note, Epstein-Barr virus (EBV) infection is closely associated with almost all of the undifferentiated NPC cases. Over the past three decades, radiation therapy and chemotherapy have formed the cornerstone of NPC treatment. However, recent advancements in immunotherapy have introduced a range of promising approaches for managing NPC. In light of these developments, it has become evident that a deeper understanding of the tumor microenvironment (TME) is crucial. The TME serves a dual function, acting as a promoter of tumorigenesis while also orchestrating immunosuppression, thereby facilitating cancer progression and enabling immune evasion. Consequently, a comprehensive comprehension of the TME and its intricate involvement in the initiation, progression, and metastasis of NPC is imperative for the development of effective anticancer drugs. Moreover, given the complexity of TME and the inter-patient heterogeneity, personalized treatment should be designed to maximize therapeutic efficacy and circumvent drug resistance. This review aims to provide an in-depth exploration of the TME within the context of EBV-induced NPC, with a particular emphasis on its pivotal role in regulating intercellular communication and shaping treatment responses. Additionally, the review offers a concise summary of drug resistance mechanisms and potential strategies for their reversal, specifically in relation to chemoradiation therapy, targeted therapy, and immunotherapy. Furthermore, recent advances in clinical trials pertaining to NPC are also discussed.
Mapping of multiple neurotransmitter receptor subtypes and distinct protein complexes to the connectome
Authors: Piero Sanfilippo, Alexander J. Kim, Anuradha Bhukel, Juyoun Yoo, Pegah S. Mirshahidi, Vijaya Pandey, Harry Bevir, Ashley Yuen, Parmis S. Mirshahidi, Peiyi Guo, Hong-Sheng Li, James A. Wohlschlegel, Yoshinori Aso, S. Lawrence Zipursky
Journal: Neuron (2024)

Neurons express various combinations of neurotransmitter receptor (NR) subunits and receive inputs from multiple neuron types expressing different neurotransmitters. Localizing NR subunits to specific synaptic inputs has been challenging. Here, we use epitope-tagged endogenous NR subunits, expansion light-sheet microscopy, and electron microscopy (EM) connectomics to molecularly characterize synapses in Drosophila. We show that in directionally selective motion-sensitive neurons, different multiple NRs elaborated a highly stereotyped molecular topography with NR localized to specific domains receiving cell-type-specific inputs. Developmental studies suggested that NRs or complexes of them with other membrane proteins determine patterns of synaptic inputs. In support of this model, we identify a transmembrane protein selectively associated with a subset of spatially restricted synapses and demonstrate its requirement for synapse formation through genetic analysis. We propose that mechanisms that regulate the precise spatial distribution of NRs provide a molecular cartography specifying the patterns of synaptic connections onto dendrites.
A randomized, controlled pilot study of oral roflumilast compared with intramuscular methotrexate for plaque and scalp psoriasis
Authors: Dina G. Saadi, Mohamed H.M. EL-Komy, Hadeer Khedr, Nevine Shawky, Amira Aly Hegazy, Yousra Azzazi, Aya M. AlOrbani
Journal: Journal of the American Academy of Dermatology (2024)
Efficacy and safety of apremilast in pediatric patients with moderate-to-severe plaque psoriasis: 16-week results from SPROUT, a randomized controlled trial
Authors: Loretta Fiorillo, Emily Becker, Raul de Lucas, Anna Belloni-Fortina, Susana Armesto, Boni Elewski, Peter Maes, Rajneet K. Oberoi, Maria Paris, Wendy Zhang, Zuoshun Zhang, Lisa Arkin
Journal: Journal of the American Academy of Dermatology (2024)

Background Approved systemic treatment options are limited for pediatric patients with moderate to severe plaque psoriasis. Objective To assess the efficacy and safety of apremilast over 16 weeks in pediatric patients with plaque psoriasis. Methods SPROUT (NCT03701763) was a phase 3, multicenter, randomized, double-blind, placebo-controlled study of apremilast in patients aged 6–17 years with moderate-to-severe psoriasis (Psoriasis Area and Severity Index [PASI] ≥12, body surface area ≥10%, static Physician Global Assessment [sPGA] ≥3) inadequately controlled by/inappropriate for topical therapy. Patients were stratified by age group and randomized (2:1) to apremilast (20 or 30 mg BID based on weight) or placebo for 16 weeks, followed by apremilast extension to 52 weeks. Results Of 245 patients randomized (apremilast: 163; placebo: 82), 221 (90%) completed the double-blind phase (apremilast: 149; placebo: 72). Significantly more patients achieved sPGA response and ≥75% reduction in PASI with apremilast than placebo, regardless of baseline age, weight, or disease severity. No new safety signals were observed. Limitations Sample size of subgroup analyses. Conclusions Improvements in global disease activity and skin involvement were significantly greater in pediatric patients treated with apremilast versus placebo. Adverse events were consistent with the known apremilast safety profile.
Injectable Bioadhesive Photocrosslinkable Hydrogels with Sustained Release of Kartogenin to Promote Chondrogenic Differentiation and Partial‐Thickness Cartilage Defects Repair
Authors: Qian Han, Jiahui He, Lang Bai, Ying Huang, Baojun Chen, Zhenlong Li, Meiguang Xu, Qiaonan Liu, Shuai Wang, Nuanyang Wen, Jing Zhang, Baolin Guo, Zhanhai Yin
Journal: Advanced Healthcare Materials (2024)

Abstract Partial‐thickness cartilage defect (PTCD) is a common and formidable clinical challenge without effective therapeutic approaches. The inherent anti‐adhesive characteristics of the extracellular matrix within cartilage pose a significant impediment to the integration of cells or biomaterials with the native cartilage during cartilage repair. Here, an injectable photocrosslinked bioadhesive hydrogel, consisting of gelatin methacryloyl (GM), acryloyl‐6‐aminocaproic acid‐ g ‐N‐hydroxysuccinimide (AN), and poly(lactic‐ co ‐glycolic acid) microspheres loaded with kartogenin (KGN) (abbreviated as GM/AN/KGN hydrogel), is designed to enhance interfacial integration and repair of PTCD. After injected in situ at the irregular defect, a stable and robust hydrogel network is rapidly formed by ultraviolet irradiation, and it can be quickly and tightly adhered to native cartilage through amide bonds. The hydrogel exhibits good adhesion strength up to 27.25 ± 1.22 kPa by lap shear strength experiments. The GM/AN/KGN hydrogel demonstrates good adhesion, low swelling, resistance to fatigue, biocompatibility, and chondrogenesis properties in vitro. A rat model with PTCD exhibits restoration of a smoother surface, stable seamless integration, and abundant aggrecan and type II collagen production. The injectable stable adhesive hydrogel with long‐term chondrogenic differentiation capacity shows great potential to facilitate repair of PTCD.
Modulation of Interleukin‐23 Signaling With Guselkumab in <scp>Biologic‐Naive</scp> Patients Versus Tumor Necrosis Factor Inhibitor–Inadequate Responders With Active Psoriatic Arthritis
Authors: Stefan Siebert, Laura C. Coates, Georg Schett, Siba P. Raychaudhuri, Warner Chen, Sheng Gao, Loqmane Seridi, Soumya D. Chakravarty, May Shawi, Frederic Lavie, Mohamed Sharaf, Miriam Zimmermann, Alexa P. Kollmeier, Xie L. Xu, Proton Rahman, Philip J. Mease, Atul Deodhar
Journal: Arthritis & Rheumatology (2024)

Objective We assessed and compared immunologic differences and associations with clinical response to guselkumab, a fully human interleukin (IL)–23p19 subunit inhibitor, in participants with active psoriatic arthritis (PsA) who were biologic‐naive or had inadequate response to tumor necrosis factor inhibitors (TNFi‐IR). Methods Serum biomarker levels at baseline and after treatment with guselkumab 100 mg every 8 weeks were compared between biologic‐naive (n = 251) and TNFi‐IR (n = 93) subgroups identified in the pooled DISCOVER‐1/DISCOVER‐2/COSMOS data set. Baseline biomarker levels determined by achievement of week 24 clinical responses (≥75%/90% improvement in Psoriasis Area and Severity Index [PASI 75/90], Investigator's Global Assessment [IGA] of psoriasis score 0/1 and ≥2‐point improvement], ≥20% improvement in American College of Rheumatology criteria [ACR20]) were compared between prior treatment subgroups. Results Baseline IL‐22, TNFα, and beta defensin‐2 (BD‐2) levels were significantly lower in biologic‐naive than in TNFi‐IR participants. With guselkumab, week 24 IL‐17A, IL‐17F, IL‐22, serum amyloid A, C‐reactive protein, IL‐6, and BD‐2 levels were significantly reduced from baseline in biologic‐naive and TNFi‐IR participants (≥1.4‐fold difference, nominal P &lt; 0.05). Clinical responders to guselkumab exhibited significantly higher baseline levels of several biomarkers than nonresponders (IL‐17A, IL‐17F, BD‐2 in biologic‐naive PASI 90 responders; IL‐17A, BD‐2 in TNFi‐IR IGA 0/1 responders; IL‐22, BD‐2 in TNFi‐IR PASI 90 responders [nominal P &lt; 0.05]) and trended higher in TNFi‐IR ACR20 responders. Conclusion Guselkumab modulates IL‐23 signaling and provides consistent pharmacodynamic effects in both biologic‐naive and TNFi‐IR PsA patients. Significantly elevated baseline IL‐22, TNFα, and BD‐2 levels and associations between baseline IL‐22, IL‐17A, and BD‐2 levels and skin responses to guselkumab suggest greater dysregulation of IL‐23/Th17 signaling in patients with TNFi‐IR.
Engineering Dual‐Responsive Prodrug‐MOFs as Immunogenic Cell Death Initiator for Enhancing Cancer Immunotherapy
Authors: Xiaochun Hu, Ruihao Li, Jie Liu, Kang Fang, Chunyan Dong, Shuo Shi
Journal: Advanced Healthcare Materials (2024)

Abstract In recent years, the anticancer effects of disulfiram, a clinical drug for anti‐alcoholism, are confirmed. However, several defects limit the clinical translation of disulfiram obviously, such as Cu(II)‐dependent anticancer activity, instability, and non‐selectivity for cancer cells. Herein, a phosphate and hydrogen peroxide dual‐responsive nanoplatform (PCu‐HA‐DQ) is reported, which is constructed by encapsulating disulfiram prodrug (DQ) and modifying hyaluronic acid (HA) on copper doping metal–organic frameworks (PCu MOFs). PCu‐HA‐DQ is expected to accumulate in tumor by targeting CD‐44 receptors and enable guidance with magnetic resonance imaging. Inside the tumor, Cu(DTC) 2 will be generated in situ based on a dual‐responsive reaction. In detail, the high concentration of phosphate can induce the release of DQ, after that, the intracellular hydrogen peroxide will further mediate the generation of Cu(DTC) 2 . In vitro and in vivo results indicate PCu‐HA‐DQ can induce the apoptosis as well as immunogenic cell death (ICD) of tumor cells distinctly, leading to enhanced immune checkpoint inhibitor (ICI) efficacy by combining the anti‐programmed death‐1 antibody. This work provides a portable strategy to construct a dual‐responsive nanoplatform integrating tumor‐targeted ability and multi‐therapy, and the designed nanoplatform is also an ICD inducer, which presents a prospect for boosting systemic antitumor immunity and ICI efficacy.