tbuckley/cabot-search huggingface dataset:
Screen Use at Bedtime and Sleep Duration and Quality Among Youths
Authors: Bradley Brosnan, Jillian J. Haszard, Kim A. Meredith-Jones, Shay-Ruby Wickham, Barbara C. Galland, Rachael W. Taylor
Journal: JAMA Pediatrics (2024)

Importance Although questionnaire-based cross-sectional research suggests that screen time before bed correlates with poor sleep, self-reported data seem unlikely to capture the complexity of modern screen use, requiring objective night-by-night measures to advance this field. Objective To examine whether evening screen time is associated with sleep duration and quality that night in youths. Design, Setting, and Participants This repeated-measures cohort study was performed from March to December 2021 in participant homes in Dunedin, New Zealand. Participants included healthy youths aged 11 to 14.9 years. Data were analyzed from October to November 2023. Exposure Objectively measured screen time, captured using wearable or stationary video cameras from 2 hours before bedtime until the first time the youth attempted sleep (shut-eye time) over 4 nonconsecutive nights. Video data were coded using a reliable protocol (κ = 0.92) to quantify device (8 options [eg, smartphone]) and activity (10 options [eg, social media]) type. Main Outcomes and Measures Sleep duration and quality were measured objectively via wrist-worn accelerometers. The association of screen use with sleep measures was analyzed on a night-by-night basis using mixed-effects regression models including participant as a random effect and adjusted for weekends. Results Of the 79 participants (47 [59.5%] male; mean [SD] age, 12.9 [1.1] years), all but 1 had screen time before bed. Screen use in the 2 hours before bed had no association with most measures of sleep health that night (eg, mean difference in total sleep time, 0 minutes [95% CI, –3 to 20 minutes] for every 10 minutes more total screen time). All types of screen time were associated with delayed sleep onset but particularly interactive screen use (mean difference, 10 minutes; 95% CI, 4 to 16 minutes for every additional 10 minutes of interactive screen time). Every 10 minutes of additional screen time in bed was associated with shorter total sleep time (mean difference, –3 minutes; 95% CI, –6 to –1 minute). The mean difference in total sleep time was −9 minutes (95% CI, −16 to −2 minutes) for every 10 minutes of interactive screen use and −4 minutes (95% CI, −7 to 0 minutes) for passive screen use. In particular, gaming (mean difference, –17 minutes; 95% CI, –28 to –7 minutes for every 10 minutes of gaming) and multitasking (mean difference, −35 minutes; 95% CI, –67 to –4 minutes on nights with vs without multitasking) were associated with less total sleep time. Conclusions and Relevance In this repeated-measures cohort study, use of an objective method showed that screen time once in bed was associated with impairment of sleep, especially when screen time was interactive or involved multitasking. These findings suggest that current sleep hygiene recommendations to restrict all screen time before bed seem neither achievable nor appropriate.
Ultrathin BSA‐Stabilized Black Phosphorous Nanoreactor Boosts Mild‐Temperature Photothermal Therapy Through Modulation of Cellular Self‐Defense Fate
Authors: Guoping Jia, Qinghe Wu, Mengfei Hou, Yifei Jiang, Huizhen Yang, Meng Li, Xubo Wu, Chunfu Zhang
Journal: Advanced Healthcare Materials (2024)

Abstract Mild‐temperature photothermal therapy (mild‐PTT, 42–45 °C) offers a higher level of biosafety. However, its therapeutic effects are compromised by the heat shock response (HSR), a cellular self‐defense mechanism, which triggers the overexpression of heat shock proteins (HSPs) with the capacity of repairing the damaged tumor cells. Herein, this work fabricates a novel nanoreactor by incorporating up‐conversion nanoparticles (UCNPs), chlorin e6 (Ce6), and glucose oxidase (GOx) onto the ultrathin black phosphorus nanosheet (BPNS) (denoted as GOx‐BUC). This nanoreactor amplifies mild‐PTT effects under irradiation with an 808 nm laser, modulating HSPs‐mediated cellular self‐defense fate. On one hand, upon irradiation with a 980 nm laser, UCNPs can transfer energy to excite Ce6, leading to the generation of ROS burst, which achieves indiscriminate damage to HSPs activity in deeper tumor tissues. On the other hand, GOx can consume glucose, thereby depleting the ATP energy supply and further suppressing HSPs expression. Consequently, GOx‐BUC exhibits excellent anti‐tumor efficacy under mild temperature in a human colorectal cancer mouse model, resulting in complete tumor inhibition with negligible side effects. This black phosphorous nanoreactor, featuring dual‐track HSPs destruction functionality, introduces novel perspectives for enhancing mild‐PTT effectiveness while maintaining high biosafety.
Implementation of a Secure Firearm Storage Program in Pediatric Primary Care
Authors: Rinad S. Beidas, Kristin A. Linn, Jennifer M. Boggs, Steven C. Marcus, Katelin Hoskins, Shari Jager-Hyman, Christina Johnson, Melissa Maye, LeeAnn Quintana, Courtney Benjamin Wolk, Leslie Wright, Celeste Pappas, Arne Beck, Katy Bedjeti, Alison M. Buttenheim, Matthew F. Daley, Marisa Elias, Jason Lyons, Melissa Lynne Martin, Bridget McArdle, Debra P. Ritzwoller, Dylan S. Small, Nathaniel J. Williams, Shiling Zhang, Brian K. Ahmedani
Journal: JAMA Pediatrics (2024)

Increased secure firearm storage can reduce youth firearm injury and mortality, a leading cause of death for children and adolescents in the US. Despite the availability of evidence-based secure firearm storage programs and recommendations from the American Academy of Pediatrics, few pediatric clinicians report routinely implementing these programs.
Surgery and Suicide Deaths Among Patients With Cancer
Authors: Michael L. Chen, Scarlett L. Gomez, Ruth O’Hara, Esther M. John, Arden M. Morris, Allison W. Kurian, Eleni Linos
Journal: JAMA Network Open (2024)

This cohort study describes suicide incidence among patients with cancer compared with the general population and by surgical status and cancer treatment.
Harnessing cellular therapeutics for type 1 diabetes mellitus: progress, challenges, and the road ahead
Authors: Alessandro Grattoni, Gregory Korbutt, Alice A Tomei, Andrés J García, Andrew R Pepper, Cherie Stabler, Michael Brehm, Klearchos Papas, Antonio Citro, Haval Shirwan, Jeffrey R Millman, Juan Melero-Martin, Melanie Graham, Michael Sefton, Minglin Ma, Norma Kenyon, Omid Veiseh, Tejal A Desai, M Cristina Nostro, Marjana Marinac, Megan Sykes, Holger A Russ, Jon Odorico, Qizhi Tang, Camillo Ricordi, Esther Latres, Nicholas E Mamrak, Jaime Giraldo, Mark C Poznansky, Paul de Vos
Journal: Nature Reviews Endocrinology (2024)
Developing an exercise intervention to minimise hip bone mineral density loss following traumatic lower limb amputation: a Delphi study
Authors: Fearghal P Behan, Anthony M J Bull, Belinda R Beck, Katherine Brooke-Wavell, Ralph Müller, Laurence Vico, Hanna Isaksson, Nicholas C Harvey, Arjan Buis, Kate Sherman, Gemma Jefferson, Daniel J Cleather, Alison McGregor, Alexander N Bennett
Journal: British Journal of Sports Medicine (2024)

Objective To elicit expert opinion and gain consensus on specific exercise intervention parameters to minimise hip bone mineral density (BMD) loss following traumatic lower limb amputation. Methods In three Delphi rounds, statements were presented to a panel of 13 experts from six countries. Experts were identified through publications or clinical expertise. Round 1 involved participants rating their agreement with 22 exercise prescription statements regarding BMD loss post amputation using a 5-point Likert scale. Agreement was deemed as 3–4 on the scale (agree/strongly agree). Statements of &lt;50% agreement were excluded. Round 2 repeated remaining statements alongside round 1 feedback. Round 3 allowed reflection on round 2 responses considering group findings and the chance to change or maintain the resp onse. Round 3 statements reaching ≥70% agreement were defined as consensus. Results All 13 experts completed rounds 1, 2 and 3 (100% completion). Round 1 excluded 12 statements and added 1 statement (11 statements for rounds 2–3). Round 3 reached consensus on nine statements to guide future exercise interventions. Experts agreed that exercise interventions should be performed at least 2 days per week for a minimum of 6 months, including at least three different resistance exercises at an intensity of 8–12 repetitions. Interventions should include weight-bearing and multiplanar exercises, involve high-impact activities and be supervised initially. Conclusion This expert Delphi process achieved consensus on nine items related to exercise prescription to minimise hip BMD loss following traumatic lower limb amputation. These recommendations should be tested in future interventional trials.
Detection of<i>M. tuberculosis</i>DNA in TB contacts’ PBMC does not associate with blood RNA signatures for incipient tuberculosis
Authors: Joshua Rosenheim, Markos Abebe, Mulugeta Belay, Begna Tulu, Dawit Tayachew, Metasebia Tegegn, Sidra Younis, David A. Jolliffe, Abraham Aseffa, Gobena Ameni, Stephen T Reece, Mahdad Noursadeghi, Adrian R Martineau
Journal: European Respiratory Journal (2024)

Human exposure to Mycobacterium tuberculosis (Mtb) is thought to result in a spectrum of outcomes including bacillary clearance, quiescent Mtb infection, incipient tuberculosis, subclinical tuberculosis and active tuberculosis [1]. Incipient tuberculosis - defined as a prolonged asymptomatic phase of early disease preceding clinical presentation as active disease [2] – may be distinguished from quiescent Mtb infection by detection of host gene expression signatures in blood, whose presence associates with increased risk of progression to active TB [3]. We and others have previously reported detection of Mtb DNA in CD34-positive peripheral blood mononuclear cells (PBMC) of asymptomatic TB-exposed adults with normal chest radiographs [4–6]. Footnotes This manuscript has recently been accepted for publication in the European Respiratory Journal . It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article. Conflict of Interest: A. Versi has nothing to disclose. Conflict of interest: STR has a pending patent in relation to detection of M. tuberculosis infection in peripheral blood. MN and ARM hold a patent in relation to blood transcriptomic biomarkers of tuberculosis. MN reports grants from the Wellcome Trust during conduct of the study. All other authors have no competing interests to declare. The views expressed are those of the authors and not necessarily those of the United Kingdom Medical Research Council or the United Kingdom Department of Health.
Single-nucleus transcriptomic profiling of human orbitofrontal cortex reveals convergent effects of aging and psychiatric disease
Authors: Anna S. Fröhlich, Nathalie Gerstner, Miriam Gagliardi, Maik Ködel, Natan Yusupov, Natalie Matosin, Darina Czamara, Susann Sauer, Simone Roeh, Vanessa Murek, Chris Chatzinakos, Nikolaos P. Daskalakis, Janine Knauer-Arloth, Michael J. Ziller, Elisabeth B. Binder
Journal: Nature Neuroscience (2024)

Abstract Aging is a complex biological process and represents the largest risk factor for neurodegenerative disorders. The risk for neurodegenerative disorders is also increased in individuals with psychiatric disorders. Here, we characterized age-related transcriptomic changes in the brain by profiling ~800,000 nuclei from the orbitofrontal cortex from 87 individuals with and without psychiatric diagnoses and replicated findings in an independent cohort with 32 individuals. Aging affects all cell types, with LAMP5 + LHX6 + interneurons, a cell-type abundant in primates, by far the most affected. Disrupted synaptic transmission emerged as a convergently affected pathway in aged tissue. Age-related transcriptomic changes overlapped with changes observed in Alzheimer’s disease across multiple cell types. We find evidence for accelerated transcriptomic aging in individuals with psychiatric disorders and demonstrate a converging signature of aging and psychopathology across multiple cell types. Our findings shed light on cell-type-specific effects and biological pathways underlying age-related changes and their convergence with effects driven by psychiatric diagnosis.
Monocytes Reprogrammed by 4-PBA Potently Contribute to the Resolution of Inflammation and Atherosclerosis
Authors: Shuo Geng, Ran Lu, Yao Zhang, Yajun Wu, Ling Xie, Blake A. Caldwell, Kisha Pradhan, Ziyue Yi, Jacqueline Hou, Feng Xu, Xian Chen, Liwu Li
Journal: Circulation Research (2024)

Chronic inflammation initiated by inflammatory monocytes underlies the pathogenesis of atherosclerosis. However, approaches that can effectively resolve chronic low-grade inflammation targeting monocytes are not readily available. The small chemical compound 4-phenylbutyric acid (4-PBA) exhibits broad anti-inflammatory effects in reducing atherosclerosis. Selective delivery of 4-PBA reprogrammed monocytes may hold novel potential in providing targeted and precision therapeutics for the treatment of atherosclerosis.
Developing clinical prediction models: a step-by-step guide
Authors: Orestis Efthimiou, Michael Seo, Konstantina Chalkou, Thomas Debray, Matthias Egger, Georgia Salanti
Journal: BMJ (2024)

Predicting future outcomes of patients is essential to clinical practice, with many prediction models published each year. Empirical evidence suggests that published studies often have severe methodological limitations, which undermine their usefulness. This article presents a step-by-step guide to help researchers develop and evaluate a clinical prediction model. The guide covers best practices in defining the aim and users, selecting data sources, addressing missing data, exploring alternative modelling options, and assessing model performance. The steps are illustrated using an example from relapsing-remitting multiple sclerosis. Comprehensive R code is also provided.
Bile acids impact the microbiota, host, and <i>C. difficile</i> dynamics providing insight into mechanisms of efficacy of FMTs and microbiota-focused therapeutics
Authors: Arthur S. McMillan, Casey M. Theriot
Journal: Gut Microbes (2024)

Clostridioides difficile is a major nosocomial pathogen, causing significant morbidity and mortality worldwide. Antibiotic usage, a major risk factor for Clostridioides difficile infection (CDI), disrupts the gut microbiota, allowing C. difficile to proliferate and cause infection, and can often lead to recurrent CDI (rCDI). Fecal microbiota transplantation (FMT) and live biotherapeutic products (LBPs) have emerged as effective treatments for rCDI and aim to restore colonization resistance provided by a healthy gut microbiota. However, much is still unknown about the mechanisms mediating their success. Bile acids, extensively modified by gut microbes, affect C. difficile's germination, growth, and toxin production while also shaping the gut microbiota and influencing host immune responses. Additionally, microbial interactions, such as nutrient competition and cross-feeding, contribute to colonization resistance against C. difficile and may contribute to the success of microbiota-focused therapeutics. Bile acids as well as other microbial mediated interactions could have implications for other diseases being treated with microbiota-focused therapeutics. This review focuses on the intricate interplay between bile acid modifications, microbial ecology, and host responses with a focus on C. difficile, hoping to shed light on how to move forward with the development of new microbiota mediated therapeutic strategies to combat rCDI and other intestinal diseases.
Fecal let-7b and miR-21 directly modulate the intestinal microbiota, driving chronic inflammation
Authors: Maite Casado-Bedmar, Maryline Roy, Louis Berthet, Jean-Pierre Hugot, Chunhua Yang, Hana Manceau, Katell Peoc’h, Benoit Chassaing, Didier Merlin, Emilie Viennois
Journal: Gut Microbes (2024)

Inflammatory bowel diseases (IBD) etiology is multifactorial. Luminal microRNAs (miRNAs) have been suspected to play a role in the promotion of chronic inflammation, but the extent to which fecal miRNAs are interacting with the intestinal ecosystem in a way that contribute to diseases, including IBD, remains unknown. Here, fecal let-7b and miR-21 were found elevated, associated with inflammation, and correlating with multiple bacteria in IBD patients and IL-10–/– mice, model of spontaneous colitis. Using an in vitro microbiota modeling system, we revealed that these two miRNAs can directly modify the composition and function of complex human microbiota, increasing their proinflammatory potential. In vivo investigations revealed that luminal increase of let-7b drastically alters the intestinal microbiota and enhances macrophages' associated proinflammatory cytokines (TNF, IL-6, and IL-1β). Such proinflammatory effects are resilient and dependent on the bacterial presence. Moreover, we identified that besides impairing the intestinal barrier function, miR-21 increases myeloperoxidase and antimicrobial peptides secretion, causing intestinal dysbiosis. More importantly, in vivo inhibition of let-7b and miR-21 with anti-miRNAs significantly improved the intestinal mucosal barrier function and promoted a healthier host-microbiota interaction in the intestinal lining, which altogether conferred protection against colitis. In summary, we provide evidence of the functional significance of fecal miRNAs in host-microbiota communication, highlighting their therapeutic potential in intestinal inflammation and dysbiosis-related conditions, such as IBD.
Ethanol-induced changes to the gut microbiome compromise the intestinal homeostasis: a review
Authors: Konrad Sosnowski, Adam Przybyłkowski
Journal: Gut Microbes (2024)

The intestine is the largest organ in terms of surface area in the human body. It is responsible not only for absorbing nutrients but also for protection against the external world. The gut microbiota is essential in maintaining a properly functioning intestinal barrier, primarily through producing its metabolites: short-chain fatty acids, bile acids, and tryptophan derivatives. Ethanol overconsumption poses a significant threat to intestinal health. Not only does it damage the intestinal epithelium, but, maybe foremostly, it changes the gut microbiome. Those ethanol-driven changes shift its metabolome, depriving the host of the protective effect the physiological gut microbiota has. This literature review discusses the impact of ethanol consumption on the gut, the gut microbiota, and its metabolome, providing a comprehensive overview of the mechanisms through which ethanol disrupts intestinal homeostasis and discussing potential avenues for new therapeutic intervention.
Highlighted research articles
Journal: Blood Cancer Discovery (2024)

In This Issue| September 03 2024 Highlighted research articles Author & Article Information Online ISSN: 2643-3249 Print ISSN: 2643-3230 ©2024 American Association for Cancer Research2024American Association for Cancer Research Blood Cancer Discov (2024) 5 (5): 302. https://doi.org/10.1158/2643-3230.BCD-5-5-ITI Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Facebook Twitter LinkedIn Email Tools Icon Tools Get Permissions Cite Icon Cite Search Site Article Versions Icon Versions Version of Record September 3 2024 Citation Highlighted research articles. Blood Cancer Discov 1 September 2024; 5 (5): 302. https://doi.org/10.1158/2643-3230.BCD-5-5-ITI Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest Search Advanced Search Aberrant turnover of cellular proteins can drive lymphomagenesis. Kelch-like family member 6 (KLHL6) encodes a substrate-determining module for a powerful protein degradation machinery with undetermined targets, and it is recurrently mutated in diffuse large B-cell lymphoma (DLBCL). By applying high-throughput proteomic screens and functional studies, Meriranta and colleagues revealed that KLHL6 targets and downregulates B-cell receptor (BCR). In B cells, selected KLHL6 mutants localized abnormally, resulting in elevated plasma membrane BCR levels that fueled BCR signaling. Loss of KLHL6 expression characterized activated B-cell–like DLBCLs with poor outcomes and associated with a targetable phenotype with high BCR levels. See article, p. 331. With axicabtagene ciloleucel (axi-cel) and tisagenlecleucel (tisa-cel) now approved for large B-cell lymphoma (LBCL), criteria for choosing the optimal CAR T-cell therapy become a pressing clinical question. Stella and colleagues tackle it in a real-life prospective study spanning 21 institutions, matching baseline characteristics of 485 patients... You do not currently have access to this content.
Targeting SRSF10 might inhibit M2 macrophage polarization and potentiate anti‐PD‐1 therapy in hepatocellular carcinoma
Authors: Jialiang Cai, Lina Song, Feng Zhang, Suiyi Wu, Guiqi Zhu, Peiling Zhang, Shiping Chen, Junxian Du, Biao Wang, Yufan Cai, Yi Yang, Jinglei Wan, Jian Zhou, Jia Fan, Zhi Dai
Journal: Cancer Communications (2024)

Abstract Background The efficacy of immune checkpoint blockade therapy in patients with hepatocellular carcinoma (HCC) remains poor. Although serine‐ and arginine‐rich splicing factor (SRSF) family members play crucial roles in tumors, their impact on tumor immunology remains unclear. This study aimed to elucidate the role of SRSF10 in HCC immunotherapy. Methods To identify the key genes associated with immunotherapy resistance, we conducted single‐nuclear RNA sequencing, multiplex immunofluorescence, and The Cancer Genome Atlas and Gene Expression Omnibus database analyses. We investigated the biological functions of SRSF10 in immune evasion using in vitro co‐culture systems, flow cytometry, various tumor‐bearing mouse models, and patient‐derived organotypic tumor spheroids. Results SRSF10 was upregulated in various tumors and associated with poor prognosis. Moreover, SRSF10 positively regulated lactate production, and SRSF10/glycolysis/ histone H3 lysine 18 lactylation (H3K18la) formed a positive feedback loop in tumor cells. Increased lactate levels promoted M2 macrophage polarization, thereby inhibiting CD8 + T cell activity. Mechanistically, SRSF10 interacted with the 3′‐untranslated region of MYB , enhancing MYB RNA stability, and subsequently upregulating key glycolysis‐related enzymes including glucose transporter 1 ( GLUT1 ), hexokinase 1 ( HK1 ), lactate dehydrogenase A ( LDHA ), resulting in elevated intracellular and extracellular lactate levels. Lactate accumulation induced histone lactylation, which further upregulated SRSF10 expression. Additionally, lactate produced by tumors induced lactylation of the histone H3K18la site upon transport into macrophages, thereby activating transcription and enhancing pro‐tumor macrophage activity. M2 macrophages, in turn, inhibited the enrichment of CD8 + T cells and the proportion of interferon‐γ + CD8 + T cells in the tumor microenvironment (TME), thus creating an immunosuppressive TME. Clinically, SRSF10 could serve as a biomarker for assessing immunotherapy resistance in various solid tumors. Pharmacological targeting of SRSF10 with a selective inhibitor 1C8 enhanced the efficacy of programmed cell death 1 (PD‐1) monoclonal antibodies (mAbs) in both murine and human preclinical models. Conclusions The SRSF10/MYB/glycolysis/lactate axis is critical for triggering immune evasion and anti‐PD‐1 resistance. Inhibiting SRSF10 by 1C8 may overcome anti‐PD‐1 tolerance in HCC.
Epidermal Secretion-purified Biosensing Patch with Hydrogel Sebum Filtering Membrane and Unidirectional Flow Microfluidic Channels
Authors: Yuqi Wang, Ziyu Zhang, Yuqing Shi, Xiong Yu, Xinyi Zhang, Xiaohao Ma, Junjie Su, Ruochen Ding, Yuanjing Lin
Journal: Biomaterials (2024)