tbuckley/cabot-search huggingface dataset:
Correlates of protection against symptomatic SARS-CoV-2 in vaccinated children
Authors: Youjia Zhong, Alicia Y. H. Kang, Carina J. X. Tay, Hui’ En Li, Nurul Elyana, Chee Wah Tan, Wee Chee Yap, Joey M. E. Lim, Nina Le Bert, Kuan Rong Chan, Eugenia Z. Ong, Jenny G. Low, Lynette P. Shek, Elizabeth Huiwen Tham, Eng Eong Ooi
Journal: Nature Medicine (2024)

Abstract The paucity of information on longevity of vaccine-induced immune responses and uncertainty of the correlates of protection hinder the development of evidence-based COVID-19 vaccination policies for new birth cohorts. Here, to address these knowledge gaps, we conducted a cohort study of healthy 5–12-year-olds vaccinated with BNT162b2. We serially measured binding and neutralizing antibody titers (nAbs), spike-specific memory B cell (MBC) and spike-reactive T cell responses over 1 year. We found that children mounted antibody, MBC and T cell responses after two doses of BNT162b2, with higher antibody and T cell responses than adults 6 months after vaccination. A booster (third) dose only improved antibody titers without impacting MBC and T cell responses. Among children with hybrid immunity, nAbs and T cell responses were highest in those infected after two vaccine doses. Binding IgG titers, MBC and T cell responses were predictive, with T cells being the most important predictor of protection against symptomatic infection before hybrid immunity; nAbs only correlated with protection after hybrid immunity. The stable MBC and T cell responses over time suggest sustained protection against symptomatic SARS-CoV-2 infection, even when nAbs wane. Booster vaccinations do not confer additional immunological protection to healthy children.
PD1 blockade improves survival and CD8+ cytotoxic capacity, without increasing inflammation, during normal microbial experience in old mice
Authors: Korbyn J. V. Dahlquist, Matthew A. Huggins, Matthew J. Yousefzadeh, Carolina Soto-Palma, Stephanie H. Cholensky, Mark Pierson, Declan M. Smith, Sara E. Hamilton, Christina D. Camell
Journal: Nature Aging (2024)
Vision–language foundation model for echocardiogram interpretation
Authors: Matthew Christensen, Milos Vukadinovic, Neal Yuan, David Ouyang
Journal: Nature Medicine (2024)

Abstract The development of robust artificial intelligence models for echocardiography has been limited by the availability of annotated clinical data. Here, to address this challenge and improve the performance of cardiac imaging models, we developed EchoCLIP, a vision–language foundation model for echocardiography, that learns the relationship between cardiac ultrasound images and the interpretations of expert cardiologists across a wide range of patients and indications for imaging. After training on 1,032,975 cardiac ultrasound videos and corresponding expert text, EchoCLIP performs well on a diverse range of benchmarks for cardiac image interpretation, despite not having been explicitly trained for individual interpretation tasks. EchoCLIP can assess cardiac function (mean absolute error of 7.1% when predicting left ventricular ejection fraction in an external validation dataset) and identify implanted intracardiac devices (area under the curve (AUC) of 0.84, 0.92 and 0.97 for pacemakers, percutaneous mitral valve repair and artificial aortic valves, respectively). We also developed a long-context variant (EchoCLIP-R) using a custom tokenizer based on common echocardiography concepts. EchoCLIP-R accurately identified unique patients across multiple videos (AUC of 0.86), identified clinical transitions such as heart transplants (AUC of 0.79) and cardiac surgery (AUC 0.77) and enabled robust image-to-text search (mean cross-modal retrieval rank in the top 1% of candidate text reports). These capabilities represent a substantial step toward understanding and applying foundation models in cardiovascular imaging for preliminary interpretation of echocardiographic findings.
Microbiome confounders and quantitative profiling challenge predicted microbial targets in colorectal cancer development
Authors: Raúl Y. Tito, Sara Verbandt, Marta Aguirre Vazquez, Leo Lahti, Chloe Verspecht, Verónica Lloréns-Rico, Sara Vieira-Silva, Janine Arts, Gwen Falony, Evelien Dekker, Joke Reumers, Sabine Tejpar, Jeroen Raes
Journal: Nature Medicine (2024)

Despite substantial progress in cancer microbiome research, recognized confounders and advances in absolute microbiome quantification remain underused; this raises concerns regarding potential spurious associations. Here we study the fecal microbiota of 589 patients at different colorectal cancer (CRC) stages and compare observations with up to 15 published studies (4,439 patients and controls total). Using quantitative microbiome profiling based on 16S ribosomal RNA amplicon sequencing, combined with rigorous confounder control, we identified transit time, fecal calprotectin (intestinal inflammation) and body mass index as primary microbial covariates, superseding variance explained by CRC diagnostic groups. Well-established microbiome CRC targets, such as Fusobacterium nucleatum, did not significantly associate with CRC diagnostic groups (healthy, adenoma and carcinoma) when controlling for these covariates. In contrast, the associations of Anaerococcus vaginalis, Dialister pneumosintes, Parvimonas micra, Peptostreptococcus anaerobius, Porphyromonas asaccharolytica and Prevotella intermedia remained robust, highlighting their future target potential. Finally, control individuals (age 22-80 years, mean 57.7 years, standard deviation 11.3) meeting criteria for colonoscopy (for example, through a positive fecal immunochemical test) but without colonic lesions are enriched for the dysbiotic Bacteroides2 enterotype, emphasizing uncertainties in defining healthy controls in cancer microbiome research. Together, these results indicate the importance of quantitative microbiome profiling and covariate control for biomarker identification in CRC microbiome studies.
Atherosclerosis Is a Smooth Muscle Cell–Driven Tumor-Like Disease
Authors: Huize Pan, Sebastian E. Ho, Chenyi Xue, Jian Cui, Quinian S. Johanson, Nadja Sachs, Leila S. Ross, Fang Li, Robert A. Solomon, E. Sander Connolly, Virendra I. Patel, Lars Maegdefessel, Hanrui Zhang, Muredach P. Reilly
Journal: Circulation (2024)

BACKGROUND: Atherosclerosis, a leading cause of cardiovascular disease, involves the pathological activation of various cell types, including immunocytes (eg, macrophages and T cells), smooth muscle cells (SMCs), and endothelial cells. Accumulating evidence suggests that transition of SMCs to other cell types, known as phenotypic switching, plays a central role in atherosclerosis development and complications. However, the characteristics of SMC-derived cells and the underlying mechanisms of SMC transition in disease pathogenesis remain poorly understood. Our objective is to characterize tumor cell–like behaviors of SMC-derived cells in atherosclerosis, with the ultimate goal of developing interventions targeting SMC transition for the prevention and treatment of atherosclerosis. METHODS: We used SMC lineage tracing mice and human tissues and applied a range of methods, including molecular, cellular, histological, computational, human genetics, and pharmacological approaches, to investigate the features of SMC-derived cells in atherosclerosis. RESULTS: SMC-derived cells in mouse and human atherosclerosis exhibit multiple tumor cell–like characteristics, including genomic instability, evasion of senescence, hyperproliferation, resistance to cell death, invasiveness, and activation of comprehensive cancer-associated gene regulatory networks. Specific expression of the oncogenic mutant Kras G12D in SMCs accelerates phenotypic switching and exacerbates atherosclerosis. Furthermore, we provide proof of concept that niraparib, an anticancer drug targeting DNA damage repair, attenuates atherosclerosis progression and induces regression of lesions in advanced disease in mouse models. CONCLUSIONS: Our findings demonstrate that atherosclerosis is an SMC-driven tumor-like disease, advancing our understanding of its pathogenesis and opening prospects for innovative precision molecular strategies aimed at preventing and treating atherosclerotic cardiovascular disease.
Evaluating pharmacological treatments for excessive daytime sleepiness in obstructive sleep apnea: A comprehensive network meta-analysis and systematic review
Authors: Seyed Sina Neshat, Afshin Heidari, Mario Henriquez-Beltran, Kripa Patel, Brendon Colaco, Vichaya Arunthari, Alejandra Yu Lee Mateus, Joseph Cheung, Gonzalo Labarca
Journal: Sleep Medicine Reviews (2024)
Sweet, bloody consumption – what we eat and how it affects vascular ageing, the BBB and kidney health in CKD
Authors: Angelina Schwarz, Leah Hernandez, Samsul Arefin, Elisa Sartirana, Anna Witasp, Annika Wernerson, Peter Stenvinkel, Karolina Kublickiene
Journal: Gut Microbes (2024)

In today's industrialized society food consumption has changed immensely toward heightened red meat intake and use of artificial sweeteners instead of grains and vegetables or sugar, respectively. These dietary changes affect public health in general through an increased incidence of metabolic diseases like diabetes and obesity, with a further elevated risk for cardiorenal complications. Research shows that high red meat intake and artificial sweeteners ingestion can alter the microbial composition and further intestinal wall barrier permeability allowing increased transmission of uremic toxins like p-cresyl sulfate, indoxyl sulfate, trimethylamine n-oxide and phenylacetylglutamine into the blood stream causing an array of pathophysiological effects especially as a strain on the kidneys, since they are responsible for clearing out the toxins. In this review, we address how the burden of the Western diet affects the gut microbiome in altering the microbial composition and increasing the gut permeability for uremic toxins and the detrimental effects thereof on early vascular aging, the kidney per se and the blood-brain barrier, in addition to the potential implications for dietary changes/interventions to preserve the health issues related to chronic diseases in future.
The effects of inhaled corticosteroids on healthy airways
Authors: Emanuele Marchi, Timothy S. C. Hinks, Matthew Richardson, Latifa Khalfaoui, Fiona A. Symon, Poojitha Rajasekar, Rachel Clifford, Beverley Hargadon, Cary D. Austin, Julia L. MacIsaac, Michael S. Kobor, Salman Siddiqui, Jordan S. Mar, Joseph R. Arron, David F. Choy, Peter Bradding
Journal: Allergy (2024)

The effects of inhaled corticosteroids (ICS) on healthy airways are poorly defined.
Tissue‐Engineered Microvessels: A Review of Current Engineering Strategies and Applications
Authors: Nan Zhao, Alexander F. Pessell, Ninghao Zhu, Peter C. Searson
Journal: Advanced Healthcare Materials (2024)

Microvessels, including arterioles, capillaries, and venules, play an important role in regulating blood flow, enabling nutrient and waste exchange, and facilitating immune surveillance. Due to their important roles in maintaining normal function in human tissues, a substantial effort has been devoted to developing tissue-engineered models to study endothelium-related biology and pathology. Various engineering strategies have been developed to recapitulate the structural, cellular, and molecular hallmarks of native human microvessels in vitro. In this review, recent progress in engineering approaches, key components, and culture platforms for tissue-engineered human microvessel models is summarized. Then, tissue-specific models, and the major applications of tissue-engineered microvessels in development, disease modeling, drug screening and delivery, and vascularization in tissue engineering, are reviewed. Finally, future research directions for the field are discussed.
Glycemic Control, Cognitive Aging, and Impairment Among Diverse Hispanic/Latino Individuals: Study of Latinos– Investigation of Neurocognitive Aging (Hispanic Community Health Study/Study of Latinos)
Authors: Hector M. González, Wassim Tarraf, Ariana M. Stickel, Alejandra Morlett, Kevin A. González, Alberto R. Ramos, Tatjana Rundek, Linda C. Gallo, Gregory A. Talavera, Martha L. Daviglus, Richard B. Lipton, Carmen Isasi, Melissa Lamar, Donglin Zeng, Charles DeCarli
Journal: Diabetes Care (2024)

Hispanic/Latino individuals in the U.S. have the highest prevalence of undiagnosed and untreated diabetes and are at increased risk for cognitive impairment. In this study, we examine glycemic control in relation to cognitive aging and impairment in a large prospective cohort of middle-aged and older Hispanic/Latino individuals of diverse heritages.
Diagnosis, treatment, and surveillance of Diamond-Blackfan anaemia syndrome: international consensus statement
Authors: Marcin W Wlodarski, Adrianna Vlachos, Jason E Farrar, Lydie M Da Costa, Antonis Kattamis, Irma Dianzani, Cristina Belendez, Sule Unal, Hannah Tamary, Ramune Pasauliene, Dagmar Pospisilova, Josu de la Fuente, Deena Iskander, Lawrence Wolfe, Johnson M Liu, Akiko Shimamura, Katarzyna Albrecht, Birgitte Lausen, Anne Grete Bechensteen, Ulf Tedgard, Alexander Puzik, Paola Quarello, Ugo Ramenghi, Marije Bartels, Heinz Hengartner, Roula A Farah, Mahasen Al Saleh, Amir Ali Hamidieh, Wan Yang, Etsuro Ito, Hoon Kook, Galina Ovsyannikova, Leo Kager, Pierre-Emmanuel Gleizes, Jean-Hugues Dalle, Brigitte Strahm, Charlotte M Niemeyer, Jeffrey M Lipton, Thierry M Leblanc
Journal: The Lancet Haematology (2024)
Layer‐by‐Layer Assembly of Renal‐Targeted Polymeric Nanoparticles for Robust Arginase‐2 Knockdown and Contrast‐Induced Acute Kidney Injury Prevention
Authors: Xu‐rui Gu, Yi‐fan Tai, Zhen Liu, Xin‐yan Zhang, Kun Liu, Ling‐yun Zhou, Wen‐jun Yin, Yi‐xuan Deng, De‐ling Kong, Adam C. Midgley, Xiao‐cong Zuo
Journal: Advanced Healthcare Materials (2024)

The mitochondrial enzyme arginase-2 (Arg-2) is implicated in the pathophysiology of contrast-induced acute kidney injury (CI-AKI). Therefore, Arg-2 represents a candid target for CI-AKI prevention. Here, layer-by-layer (LbL) assembled renal-targeting polymeric nanoparticles are developed to efficiently deliver small interfering RNA (siRNA), knockdown Arg-2 expression in renal tubules, and prevention of CI-AKI is evaluated. First, near-infrared dye-loaded poly(lactic-co-glycolic acid) (PLGA) anionic cores are electrostatically coated with cationic chitosan (CS) to facilitate the adsorption and stabilization of Arg-2 siRNA. Next, nanoparticles are coated with anionic hyaluronan (HA) to provide protection against siRNA leakage and shielding against early clearance. Sequential electrostatic layering of CS and HA improves loading capacity of Arg-2 siRNA and yields LbL-assembled nanoparticles. Renal targeting and accumulation is enhanced by modifying the outermost layer of HA with a kidney targeting peptide (HA-KTP). The resultant kidney-targeting and siRNA loaded nanoparticles (PLGA/CS/HA-KTP siRNA) exhibit proprietary accumulation in kidneys and proximal tubular cells at 24 h post-tail vein injection. In iohexol-induced in vitro and in vivo CI-AKI models, PLGA/CS/HA-KTP siRNA delivery alleviates oxidative and nitrification stress, and rescues mitochondrial dysfunction while reducing apoptosis, thereby demonstrating a robust and satisfactory therapeutic effect. Thus, PLGA/CS/HA-KTP siRNA nanoparticles offer a promising candidate therapy to protect against CI-AKI.
Injectable and rapidly expandable thrombin-decorated cryogels achieve rapid hemostasis and high survival rates in a swine model of lethal junctional hemorrhage
Authors: Syed Muntazir Andrabi, S.M. Shatil Shahriar, Al-Murtadha Al-Gahmi, Benjamin L. Wilczewski, Mark A. Carlson, Jingwei Xie
Journal: Bioactive Materials (2024)

Effective therapies are urgently needed to stabilize patients with marginally compressible junctional hemorrhage long enough to get them to the hospital alive. Herein, we report injectable and rapidly expandable cryogels consisting of polyacrylamide and thrombin (AT cryogels) created by cryo-polymerization for the efficient management of lethal junctional hemorrhage in swine. The produced cryogels have small pore sizes and highly interconnected porous architecture with robust mechanical strength. The cryogels exhibit rapid shape memory properties and prove to be resilient against fatigue. These cryogels also show high water/blood absorption capacity, fast blood clotting effect, and enhanced adhesion of red blood cells and platelets in vitro. Further, in vivo, hemostatic efficacy tests in a lethal swine junctional hemorrhage model suggest that treatment with AT cryogels, especially AT-2 cryogels, achieves the least blood loss and the highest survival rate (100 %) compared to currently employed products such as XStat® and combat gauze. The high hemostatic performance of the cryogels may be attributed to highly interconnected porous architecture with small pore size and the use of thrombin as a pro-coagulant agent. Collectively, injectable and rapidly expandable thrombin-decorated polyacrylamide-based cryogels show significant promise as hemostatic material, offering effective management of marginally compressible junctional hemorrhages in prehospital settings.
Efficacy of an Internet- and Mobile-Based Intervention for Subclinical Anxiety and Depression (ICare Prevent) with Two Guidance Formats: Results from a Three-Armed Randomized Controlled Trial
Authors: Anna-Carlotta Zarski, Kiona K. Weisel, Thomas Berger, Tobias Krieger, Michael P. Schaub, Matthias Berking, Dennis Görlich, Corinna Jacobi, David D. Ebert
Journal: Psychotherapy and Psychosomatics (2024)

&lt;b&gt;&lt;i&gt;Introduction:&lt;/i&gt;&lt;/b&gt; Limited research exists on intervention efficacy for comorbid subclinical anxiety and depressive disorders, despite their common co-occurrence. Internet- and mobile-based interventions (IMIs) are promising to reach individuals facing subclinical symptoms. &lt;b&gt;&lt;i&gt;Objective:&lt;/i&gt;&lt;/b&gt; This study aimed to evaluate the efficacy of a transdiagnostic and self-tailored IMI in reducing subclinical anxiety and depressive symptom severity with either individualized (IG-IMI) or automated (AG-IMI) guidance compared to a waitlist control group with care-as-usual access (WLC). &lt;b&gt;&lt;i&gt;Methods:&lt;/i&gt;&lt;/b&gt; Participants included 566 adults with subclinical anxiety (GAD-7 ≥ 5) and/or depressive (CES-D ≥16) symptoms, who did not meet criteria for a full-syndrome depressive or anxiety disorder. In a three-arm randomized clinical trial, participants were randomized to a cognitive behavioral 7-session IMI plus booster session with IG-IMI (&lt;i&gt;n&lt;/i&gt; = 186) or AG-IMI (&lt;i&gt;n&lt;/i&gt; = 189) or WLC (&lt;i&gt;n&lt;/i&gt; = 191). Primary outcomes included observer-rated anxiety (HAM-A) and depressive (QIDS) symptom severity 8 weeks after randomization assessed by blinded raters via telephone. Follow-up outcomes at 6 and 12 months are reported. &lt;b&gt;&lt;i&gt;Results:&lt;/i&gt;&lt;/b&gt; Symptom severity was significantly lower with small to medium effects in IG-IMI (anxiety: &lt;i&gt;d&lt;/i&gt; = 0.45, depression: &lt;i&gt;d&lt;/i&gt; = 0.43) and AG-IMI (anxiety: &lt;i&gt;d&lt;/i&gt; = 0.31, depression: &lt;i&gt;d&lt;/i&gt; = 0.32) compared to WLC. No significant differences emerged between guidance formats in primary outcomes. There was a significant effect in HAM-A after 6 months favoring AG-IMI. On average, participants completed 85.38% of IG-IMI and 77.38% of AG-IMI. &lt;b&gt;&lt;i&gt;Conclusions:&lt;/i&gt;&lt;/b&gt; A transdiagnostic, self-tailored IMI can reduce subclinical anxiety and depressive symptom severity, but 12-month long-term effects were absent. Automated guidance holds promise for enhancing the scalability of IMIs in broad prevention initiatives.
Enhanced Skills Training in Affective and Interpersonal Regulation versus Treatment as Usual for ICD-11 Complex PTSD: A Pilot Randomised Controlled Trial (The RESTORE Trial)
Authors: Thanos Karatzias, Mark Shevlin, Marylène Cloitre, Walter Busuttil, Katherine Graham, Laura Hendrikx, Philip Hyland, Natasha Biscoe, Dominic Murphy
Journal: Psychotherapy and Psychosomatics (2024)

&lt;b&gt;&lt;i&gt;Introduction:&lt;/i&gt;&lt;/b&gt; Complex PTSD (CPTSD) is a relatively new condition in ICD-11. This pilot randomised controlled trial aimed to compare a four-module intervention developed to target all symptoms of ICD-11 CPTSD, namely Enhanced Skills in Affective and Interpersonal Regulation (ESTAIR) with treatment as usual (TAU). The purpose of the study was to assess feasibility, safety, acceptability, and preliminary outcomes at the end of treatment and 3-month follow-up. &lt;b&gt;&lt;i&gt;Methods:&lt;/i&gt;&lt;/b&gt; A total of &lt;i&gt;N&lt;/i&gt; = 56 eligible veterans with CPTSD were randomised to either ESTAIR (&lt;i&gt;n&lt;/i&gt; = 28) or TAU (&lt;i&gt;n&lt;/i&gt; = 28). Linear mixed models were conducted to assess CPTSD severity, the primary outcome, as measured by the International Trauma Questionnaire (ITQ). &lt;b&gt;&lt;i&gt;Results:&lt;/i&gt;&lt;/b&gt; Treatment dropout in ESTAIR and TAU was low and equivalent (18% vs. 11%; &lt;i&gt;χ&lt;/i&gt;&lt;sup&gt;2&lt;/sup&gt; (1) = 1.19, &lt;i&gt;p&lt;/i&gt; = 0.275), and study retention was high, supporting the feasibility of the study. No serious adverse effects and very few adverse effects occurred, none of which were deemed related to the study. ESTAIR provided significantly greater reduction in CPTSD severity across time for ITQ PTSD (&lt;i&gt;p&lt;/i&gt; &amp;lt; 0.001) and DSO (&lt;i&gt;p&lt;/i&gt; &amp;lt; 0.001) symptoms. CPTSD pre-to-post effect sizes for ESTAIR were large (PTSD &lt;i&gt;d&lt;/i&gt; = 1.78; DSO &lt;i&gt;d&lt;/i&gt; = 2.00). Remission of probable CPTSD diagnosis at post-treatment was substantially greater in ESTAIR compared to TAU with only 13.6% versus 84% (&lt;i&gt;p&lt;/i&gt; &amp;lt; 0.001) retaining the diagnosis. &lt;b&gt;&lt;i&gt;Conclusion:&lt;/i&gt;&lt;/b&gt; A trial of ESTAIR versus TAU for the treatment of ICD-11 CPTSD indicates the potential efficacy of ESTAIR as well as its feasibility, safety, and acceptability.
Long Non-coding RNA NEAT1, NOD-Like Receptor Family Protein 3 Inflammasome, and Acute Kidney Injury
Authors: Rui Xue, Wai Han Yiu, Kam Wa Chan, Sarah W.Y. Lok, Yixin Zou, Jingyuan Ma, Hongyu Li, Loretta Y.Y. Chan, Xiao Ru Huang, Kar Neng Lai, Hui Yao Lan, Sydney C.W. Tang
Journal: Journal of the American Society of Nephrology (2024)

Acute kidney injury (AKI) is common in hospitalized patients and is associated with high mortality. Inflammation plays a key role in the pathophysiology of AKI. Long non-coding RNAs (lncRNAs) are increasingly recognized as regulators of the inflammatory and immune response, but its role in AKI remains unclear.