tbuckley/cabot-search huggingface dataset:
Survival Outcomes Among Patients With Hepatocellular Carcinoma in a Large Integrated US Health System
Authors: Mignote Yilma, Richie Houhong Xu, Varun Saxena, Monica Muzzin, Lue-Yen Tucker, Jeffrey Lee, Neil Mehta, Nizar Mukhtar
Journal: JAMA Network Open (2024)

Importance Hepatocellular carcinoma (HCC) is the leading oncologic cause of death among patients with cirrhosis, but large studies examining mortality trends are lacking. Objective To evaluate survival among patients with HCC in one of the largest integrated health care systems in the US. Design, Setting, and Participants This retrospective cohort study included 3441 adult patients who received a diagnosis of HCC between January 1, 2006, and December 31, 2019, with end of follow-up on December 31, 2020. The study period was further categorized as era 1, defined as 2006 to 2012, and era 2, defined as 2013 to 2019. Statistical analysis was conducted from January 2021 to June 2024. Exposures Patient demographic characteristics and disease factors. Main Outcomes and Measures All-cause and HCC-specific mortality were used as primary end points, and survival probabilities were estimated using the Kaplan-Meier method. Cox proportional hazards regression analyses were adjusted for age at diagnosis, sex, race and ethnicity, cause of disease, Barcelona Clinic Liver Cancer (BCLC) stage, alpha-fetoprotein level, and treatment type. Results Of 3441 patients with HCC, 2581 (75.0%) were men, and the median age was 65 years (IQR, 58-73 years). A total of 1195 patients (34.7%) received curative treatment, 1374 (39.9%) received noncurative treatment, and 872 (25.3%) received no treatment. During the study period, 2500 patients (72.7%) experienced all-cause mortality, and 1809 (52.6%) had HCC-specific mortality. In multivariable analysis, being 70 years of age or older (adjusted hazard ratio [AHR], 1.39; 95% CI, 1.22-1.59), male sex (AHR, 1.20; 95% CI, 1.07-1.35), BCLC stage C or D (AHR, 2.40; 95% CI, 2.15-2.67), increasing alpha-fetoprotein level (vs &amp;amp;lt;20 ng/mL; 20-99 ng/mL: AHR, 1.20; 95% CI, 1.04-1.38; ≥1000 ng/mL: AHR, 2.84; 95% CI, 2.45-3.25), noncurative treatment (AHR, 2.51; 95% CI, 2.16-2.90), and no treatment (AHR, 3.15; 95% CI, 2.64-3.76) were associated with higher all-cause mortality, while Asian or Other Pacific Islander race and ethnicity (vs non-Hispanic White; AHR, 0.76; 95% CI, 0.65-0.88) was associated with lower all-cause mortality. Survival improved in diagnosis era 2 (2013-2019; n = 2007) compared with diagnosis era 1 (2006-2012; n = 1434). Conclusions and Relevance This large, racially and ethnically diverse cohort study of patients with HCC found improving survival over time, especially among individuals with early-stage HCC receiving potentially curative treatments. This study highlights the importance of surveillance for detection of HCC at early stages, particularly among groups at risk for poorer outcomes.
Offline hippocampal reactivation during dentate spikes supports flexible memory
Authors: Stephen B McHugh, Vítor Lopes-Dos-Santos, Manfredi Castelli, Giuseppe P Gava, Sophie E Thompson, Shu K E Tam, Katja Hartwich, Brook Perry, Robert Toth, Timothy Denison, Andrew Sharott, David Dupret
Journal: Neuron (2024)
Multidimensional profiling of human T cells reveals high CD38 expression, marking recent thymic emigrants and age-related naive T cell remodeling
Authors: Pavla Bohacova, Marina Terekhova, Petr Tsurinov, Riley Mullins, Kamila Husarcikova, Irina Shchukina, Alina Ulezko Antonova, Barbora Echalar, Jan Kossl, Adam Saidu, Thomas Francis, Chelsea Mannie, Laura Arthur, Stephen D R Harridge, Daniel Kreisel, Philip A Mudd, Angela M Taylor, Coleen A McNamara, Marina Cella, Sidharth V Puram, Theo van den Broek, Femke van Wijk, Pirooz Eghtesady, Maxim N Artyomov
Journal: Immunity (2024)
Sirolimus reduces T cell cycling, immune checkpoint marker expression, and HIV-1 DNA in people with HIV
Authors: Timothy J Henrich, Ronald J Bosch, Catherine Godfrey, Hanna Mar, Apsara Nair, Michael Keefer, Carl Fichtenbaum, Daniela Moisi, Brian Clagett, Amanda M Buck, Amelia N Deitchman, Francesca Aweeka, Jonathan Z Li, Daniel R Kuritzkes, Michael M Lederman, Priscilla Y Hsue, Steven G Deeks
Journal: Cell Reports Medicine (2024)
Transport of β-amyloid from brain to eye causes retinal degeneration in Alzheimer’s disease
Authors: Qiuchen Cao, Shige Yang, Xiaowei Wang, Huaiqing Sun, Weijie Chen, Yuliang Wang, Junying Gao, Yanchi Wu, Qiuhua Yang, Xue Chen, Songtao Yuan, Ming Xiao, Maiken Nedergaard, Yuqing Huo, Qinghuai Liu
Journal: The Journal of Experimental Medicine (2024)

The eye is closely connected to the brain, providing a unique window to detect pathological changes in the brain. In this study, we discovered β-amyloid (Aβ) deposits along the ocular glymphatic system in patients with Alzheimer’s disease (AD) and 5×FAD transgenic mouse model. Interestingly, Aβ from the brain can flow into the eyes along the optic nerve through cerebrospinal fluid (CSF), causing retinal degeneration. Aβ is mainly observed in the optic nerve sheath, the neural axon, and the perivascular space, which might represent the critical steps of the Aβ transportation from the brain to the eyes. Aquaporin-4 facilitates the influx of Aβ in brain–eye transport and out-excretion of the retina, and its absence or loss of polarity exacerbates brain-derived Aβ induced damage and visual impairment. These results revealed brain-to-eye Aβ transport as a major contributor to AD retinopathy, highlighting a new therapeutic avenue in ocular and neurodegenerative disease.
Ventral hippocampal parvalbumin interneurons gate the acute anxiolytic action of the serotonergic psychedelic DOI
Authors: Praachi Tiwari, Pasha A Davoudian, Darshana Kapri, Ratna Mahathi Vuruputuri, Lindsay A Karaba, Mukund Sharma, Giulia Zanni, Angarika Balakrishnan, Pratik R Chaudhari, Amartya Pradhan, Shital Suryavanshi, Kevin G Bath, Mark S Ansorge, Antonio Fernandez-Ruiz, Alex C Kwan, Vidita A Vaidya
Journal: Neuron (2024)
Autoantibodies neutralizing type I IFNs underlie severe tick-borne encephalitis in ∼10% of patients
Authors: Adrian Gervais, Astrid Marchal, Andrea Fortova, Michaela Berankova, Lenka Krbkova, Martina Pychova, Jiri Salat, Shuxiang Zhao, Nacim Kerrouche, Tom Le Voyer, Karin Stiasny, Simon Raffl, Anne Schieber Pachart, Samira Fafi-Kremer, Simon Gravier, Davide F. Robbiani, Laurent Abel, Margaret R. MacDonald, Charles M. Rice, Gaia Weissmann, Tarek Kamal Eldin, Eva Robatscher, Elke Maria Erne, Elisabetta Pagani, Alessandro Borghesi, Anne Puel, Paul Bastard, Aurélie Velay, Martin Martinot, Yves Hansmann, Judith H. Aberle, Daniel Ruzek, Aurélie Cobat, Shen-Ying Zhang, Jean-Laurent Casanova
Journal: The Journal of Experimental Medicine (2024)

Tick-borne encephalitis (TBE) virus (TBEV) is transmitted to humans via tick bites. Infection is benign in &amp;gt;90% of the cases but can cause mild (&amp;lt;5%), moderate (&amp;lt;4%), or severe (&amp;lt;1%) encephalitis. We show here that ∼10% of patients hospitalized for severe TBE in cohorts from Austria, Czech Republic, and France carry auto-Abs neutralizing IFN-α2, -β, and/or -ω at the onset of disease, contrasting with only ∼1% of patients with moderate and mild TBE. These auto-Abs were found in two of eight patients who died and none of 13 with silent infection. The odds ratios (OR) for severe TBE in individuals with these auto-Abs relative to those without them in the general population were 4.9 (95% CI: 1.5–15.9, P &amp;lt; 0.0001) for the neutralization of only 100 pg/ml IFN-α2 and/or -ω, and 20.8 (95% CI: 4.5–97.4, P &amp;lt; 0.0001) for the neutralization of 10 ng/ml IFN-α2 and -ω. Auto-Abs neutralizing type I IFNs accounted for ∼10% of severe TBE cases in these three European cohorts.
Baiting bacteria with amino acidic and peptidic corona coated defect-engineered antimicrobial nanoclusters for optimized wound healing
Authors: Maonan Wang, Houjuan Zhu, Yuling Xue, Yanxia Duan, Hua Tian, Qi Liu, Yuzhu Zhang, Zibiao Li, Xian Jun Loh, Enyi Ye, Gang Yin, Xuemei Wang, Xianguang Ding, David Tai Leong
Journal: Bioactive Materials (2024)
Food consumption by degree of food processing and risk of type 2 diabetes mellitus: a prospective cohort analysis of the European Prospective Investigation into Cancer and Nutrition (EPIC)
Authors: Samuel J Dicken, Christina C Dahm, Daniel B Ibsen, Anja Olsen, Anne Tjønneland, Mariem Louati-Hajji, Claire Cadeau, Chloé Marques, Matthias B Schulze, Franziska Jannasch, Ivan Baldassari, Luca Manfredi, Maria Santucci de Magistris, Maria-Jose Sánchez, Carlota Castro-Espin, Daniel Rodríguez Palacios, Pilar Amiano, Marcela Guevara, Yvonne T van der Schouw, Jolanda M A Boer, W M Monique Verschuren, Stephen J Sharp, Nita G Forouhi, Nicholas J Wareham, Eszter P Vamos, Kiara Chang, Paolo Vineis, Alicia K Heath, Marc J Gunter, Geneviève Nicolas, Elisabete Weiderpass, Inge Huybrechts, Rachel L Batterham
Journal: The Lancet Regional Health - Europe (2024)
Sexual dimorphism in the relationships between intramyocardial fat, myocardial fibrosis, and exercise intolerance in heart failure with preserved ejection fraction
Authors: Arnold C.T. Ng, Xin Dong, Katlyn E. Koepp, Masaru Obokata, Hidemi Sorimachi, Graham Galloway, Philip Araoz, Victoria Delgado, Jeroen J. Bax, Barry A. Borlaug
Journal: European Journal of Heart Failure (2024)
Effect of seasonal influenza and COVID‐19 vaccination on severity and long‐term outcomes of patients with heart failure decompensations
Authors: Òscar Miró, Nicole Ivars, Begoña Espinosa, Javier Jacob, Aitor Alquézar‐Arbé, María Pilar López‐Díez, Pablo Herrero Puente, María Luisa López‐Grima, Beatriz Rodríguez, Pablo Rodríguez Fuertes, Pascual Piñera Salmerón, Josep Tost, Juan Antonio Andueza, Eva Domingo Baldrich, José Manuel Garrido, José Noceda, Francisco Javier Lucas‐Imbernon, Rocío Moyano García, Víctor Gil, Josep Masip, W. Frank Peacock, Christian Mueller, Pere Llorens
Journal: European Journal of Heart Failure (2024)
Sex differences in cardiac structure and function following acute myocardial infarction: Insights from the <scp>PARADISE</scp>‐<scp>MI</scp> echocardiographic substudy
Authors: Xiaowen Wang, Maria A. Pabon, Maja Cikes, Karola Jering, Wilfried Mullens, Lars Kober, Pardeep S. Jhund, Attila Kovacs, Bela Merkely, Yinong Zhou, John J.V. McMurray, Amil M. Shah, Sheila M. Hegde, Brian Claggett, Marc A. Pfeffer, Scott D. Solomon
Journal: European Journal of Heart Failure (2024)
Assessing acute toxicity profiles of <scp>HLA</scp>‐identical hematopoietic stem cell transplantation in pediatric patients with sickle cell anemia: A comprehensive analysis on behalf of the <scp>SFGM</scp>‐<scp>TC</scp>
Authors: M. Delafoy, J. H. Dalle, C. Pondarre, G. P. Andrieu, M. Fahd, K. Yakouben, M. Castelle, B. Koehl, B. Neven, A. Grain
Journal: American Journal of Hematology (2024)
Renaming mpox in Spanish, French, and Portuguese: using language to address stigma and racism
Authors: Jaime García-Iglesias, Angélica Cabezas-Pino, Francisco Javier Membrillo de Novales, Axel Rodrigo Bautista Pérez, Jorge Garrido Fuentes, Fernando Villaamil Pérez, Alfonso J Rodríguez-Morales, Diego Zamora Estay, Edith Guajardo Zuñiga, Lucas J Núñez Saavedra, Emilio de Benito Cañizares
Journal: The Lancet (2024)
Statistically and functionally fine-mapped blood eQTLs and pQTLs from 1,405 humans reveal distinct regulation patterns and disease relevance
Authors: Qingbo S Wang, Takanori Hasegawa, Ho Namkoong, Ryunosuke Saiki, Ryuya Edahiro, Kyuto Sonehara, Hiromu Tanaka, Shuhei Azekawa, Shotaro Chubachi, Yugo Takahashi, Saori Sakaue, Shinichi Namba, Kenichi Yamamoto, Yuichi Shiraishi, Kenichi Chiba, Hiroko Tanaka, Hideki Makishima, Yasuhito Nannya, Zicong Zhang, Rika Tsujikawa, Ryuji Koike, Tomomi Takano, Makoto Ishii, Akinori Kimura, Fumitaka Inoue, Takanori Kanai, Koichi Fukunaga, Seishi Ogawa, Seiya Imoto, Satoru Miyano, Yukinori Okada
Journal: Nature Genetics (2024)

Studying the genetic regulation of protein expression (through protein quantitative trait loci (pQTLs)) offers a deeper understanding of regulatory variants uncharacterized by mRNA expression regulation (expression QTLs (eQTLs)) studies. Here we report cis-eQTL and cis-pQTL statistical fine-mapping from 1,405 genotyped samples with blood mRNA and 2,932 plasma samples of protein expression, as part of the Japan COVID-19 Task Force (JCTF). Fine-mapped eQTLs (n = 3,464) were enriched for 932 variants validated with a massively parallel reporter assay. Fine-mapped pQTLs (n = 582) were enriched for missense variations on structured and extracellular domains, although the possibility of epitope-binding artifacts remains. Trans-eQTL and trans-pQTL analysis highlighted associations of class I HLA allele variation with KIR genes. We contrast the multi-tissue origin of plasma protein with blood mRNA, contributing to the limited colocalization level, distinct regulatory mechanisms and trait relevance of eQTLs and pQTLs. We report a negative correlation between ABO mRNA and protein expression because of linkage disequilibrium between distinct nearby eQTLs and pQTLs.
Exercise activates AMPK in mouse and human pancreatic islets to decrease senescence
Authors: Priscila Carapeto, Kanako Iwasaki, Francesko Hela, Jiho Kahng, Ana B Alves-Wagner, Roeland J W Middelbeek, Michael F Hirshman, Guy A Rutter, Laurie J Goodyear, Cristina Aguayo-Mazzucato
Journal: Nature Metabolism (2024)
A potential target for noninvasive neuromodulation of PTSD symptoms derived from focal brain lesions in veterans
Authors: Shan H Siddiqi, Noah S Philip, Stephan T Palm, David M Carreon, Amanda R Arulpragasam, Jennifer Barredo, Heather Bouchard, Michael A Ferguson, Jordan H Grafman, Rajendra A Morey, Michael D Fox
Journal: Nature Neuroscience (2024)
Defining heritability, plasticity, and transition dynamics of cellular phenotypes in somatic evolution
Authors: Joshua S Schiffman, Andrew R D'Avino, Tamara Prieto, Yakun Pang, Yilin Fan, Srinivas Rajagopalan, Catherine Potenski, Toshiro Hara, Mario L Suvà, Charles Gawad, Dan A Landau
Journal: Nature Genetics (2024)
Characterisation and prognostic impact Of ZRSR2 mutations in myeloid neoplasms
Authors: Mahmoud Yacout, Bahga Katamesh, Yazan Jabban, Rong He, David Viswanatha, Dragan Jevremovic, Patricia Greipp, Kurt Bessonen, Jeanne Palmer, James Foran, Antoine Saliba, Mehrdad Hefazi-Torghabeh, Kebede Begna, William Hogan, Mrinal Patnaik, Mithun Shah, Hassan Alkhateeb, Aref Al-Kali
Journal: Leukemia (2024)
Circulating Autoantibodies Targeting TREK-1 in Patients With Short-Coupled Ventricular Fibrillation
Authors: Jin Li, Alexandre Janin, Mona Patoughi, Nathalie Gaudreault, Lenke Kis, Hamid Moha Ou Maati, Yohan Bossé, Christian Steinberg
Journal: Circulation (2024)

Short-coupled ventricular fibrillation (SCVF) is increasingly being recognized as a distinct primary electrical disorder and cause of otherwise unexplained cardiac arrest. However, the pathophysiology of SCVF remains largely elusive. Despite extensive genetic screening, there is no convincing evidence of a robust monogenic disease gene, thus raising the speculations for alternative pathogeneses. The role of autoimmune mechanisms in SCVF has not been investigated so far. The objective of this study was to screen for circulating autoantibodies in patients with SCVF and assess their role in arrhythmogenesis.
NT-proBNP and Cardiac Troponin I, but Not Cardiac Troponin T, Are Associated With 7-Year Changes in Cardiac Structure and Function in Older Adults: The ARIC Study
Authors: Peder L. Myhre, Brian Claggett, Christie M. Ballantyne, Ron C. Hoogeveen, Elizabeth Selvin, Kunihiro Matsushita, Dalane Kitzman, Suma Konety, Thomas Mosley, Amil M. Shah
Journal: Circulation (2024)

BACKGROUND: Higher circulating concentrations of NT-proBNP (N-terminal pro-B-type natriuretic peptide) and high-sensitivity cardiac troponin T (hs-cTnT) and I (hs-cTnI) are associated with left ventricular remodeling and with incident heart failure. The associations of these cardiac biomarkers with changes in cardiac structure and function over time are uncharacterized. METHODS: Among 2006 participants in the ARIC prospective cohort study (Atherosclerosis Risk in Communities) who were free of overt cardiovascular disease and underwent echocardiography at study visits 5 (2011– 2013) and 7 (2018–2019), we assessed the associations of NT-proBNP, hs-cTnT, and hs-cTnI concentrations at visit 5 with changes in left ventricular structure and function between visits 5 and 7 (≈7-year change) using multivariable linear regression with the biomarkers modeled as restricted cubic splines. Models were adjusted for age, sex, race, body mass index, smoking, diabetes, hypertension, and renal function at visit 5; blood pressure and heart rate at both visits; and the baseline value of the echocardiographic parameter of interest. RESULTS: Mean±SD age was 74±4 years at visit 5; 61% were women; and 23% were Black adults. Median (25th–75th percentile) concentrations at visit 5 of NT-proBNP, hs-cTnT, and hs-cTnI were 87 ng/L (50–157 ng/L), 9 ng/L (6–12 ng/L), and 2.6 ng/L (1.9–3.9 ng/L). In adjusted models, elevated baseline concentrations of NT-proBNP and hs-cTnI were significantly associated with 7-year decline in left ventricular systolic function (ejection fraction, longitudinal and circumferential strain) and worsening diastolic indices. In contrast, elevated baseline concentrations of hs-cTnT were not significantly associated with 7-year changes in cardiac structure, systolic function, or diastolic function (all P &gt;0.05). CONCLUSIONS: Higher concentrations of NT-proBNP and hs-cTnI, but not hs-cTnT, were associated with greater declines in left ventricular function over ≈7 years in late life independently of traditional cardiovascular risk factors.AQ
Bone Morphogenetic Protein 9 Protects Against Myocardial Infarction by Improving Lymphatic Drainage Function and Triggering DECR1-Mediated Mitochondrial Bioenergetics
Authors: Zikun Duan, Zhouqing Huang, Wei Lei, Ke Zhang, Wei Xie, Hua Jin, Maolan Wu, Ningrui Wang, Xiaokun Li, Aimin Xu, Hao Zhou, Fan Wu, Yulin Li, Zhuofeng Lin
Journal: Circulation (2024)

BACKGROUND: BMP9 (bone morphogenetic protein 9) is a member of the TGF-β (transforming growth factor β) family of cytokines with pleiotropic effects on glucose metabolism, fibrosis, and lymphatic development. However, the role of BMP9 in myocardial infarction (MI) remains elusive. METHODS: The expressional profiles of BMP9 in cardiac tissues and plasma samples of subjects with MI were determined by immunoassay or immunoblot. The role of BMP9 in MI was determined by evaluating the impact of BMP9 deficiency and replenishment with adeno-associated virus–mediated BMP9 expression or recombinant human BMP9 protein in mice. RESULTS: We show that circulating BMP9 and its cardiac levels are markedly increased in humans and mice with MI and are negatively associated with cardiac function. It is important to note that BMP9 deficiency exacerbates left ventricular dysfunction, increases infarct size, and augments cardiac fibrosis in mice with MI. In contrast, replenishment of BMP9 significantly attenuates these adverse effects. We further demonstrate that BMP9 improves lymphatic drainage function, thereby leading to a decrease of cardiac edema. In addition, BMP9 increases the expression of mitochondrial DECR1 (2,4-dienoyl-CoA [coenzyme A] reductase 1), a rate-limiting enzyme involved in β-oxidation, which, in turn, promotes cardiac mitochondrial bioenergetics and mitigates MI-induced cardiomyocyte injury. Moreover, DECR1 deficiency exacerbates MI-induced cardiac damage in mice, whereas this adverse effect is restored by the treatment of adeno-associated virus–mediated DECR1. Consistently, DECR1 deletion abrogates the beneficial effect of BMP9 against MI-induced cardiomyopathy and cardiac damage in mice. CONCLUSIONS: These results suggest that BMP9 protects against MI by fine-tuning the multiorgan cross-talk among the liver, lymph, and the heart.
Core Components of Cardiac Rehabilitation Programs: 2024 Update: A Scientific Statement From the American Heart Association and the American Association of Cardiovascular and Pulmonary Rehabilitation
Authors: Todd M. Brown, Quinn R. Pack, Ellen Aberegg, LaPrincess C. Brewer, Yvonne R. Ford, Daniel E. Forman, Emily C. Gathright, Sherrie Khadanga, Cemal Ozemek, Randal J. Thomas
Journal: Circulation (2024)

The science of cardiac rehabilitation and the secondary prevention of cardiovascular disease has progressed substantially since the most recent American Heart Association and American Association of Cardiovascular and Pulmonary Rehabilitation update on the core components of cardiac rehabilitation and secondary prevention programs was published in 2007. In addition, the advent of new care models, including virtual and remote delivery of cardiac rehabilitation services, has expanded the ways that cardiac rehabilitation programs can reach patients. In this scientific statement, we update the scientific basis of the core components of patient assessment, nutritional counseling, weight management and body composition, cardiovascular disease and risk factor management, psychosocial management, aerobic exercise training, strength training, and physical activity counseling. In addition, in recognition that high-quality cardiac rehabilitation programs regularly monitor their processes and outcomes and engage in an ongoing process of quality improvement, we introduce a new core component of program quality. High-quality program performance will be essential to improve widely documented low enrollment and adherence rates and reduce health disparities in cardiac rehabilitation access.
Safety and efficacy of HK-660S in patients with primary sclerosing cholangitis: A randomized double-blind phase 2a trial
Authors: Woo Hyun Paik, Joo Kyung Park, Moon Jae Chung, Gunn Huh, Ce Hwan Park, Sang Hyub Lee, Heon Se Jeong, Hee Jin Kim, Do Hyun Park
Journal: Clinical and Molecular Hepatology (2024)

A clinical unmet need persists for medications capable of modulating the progression of primary sclerosing cholangitis (PSC). This study aimed to assess the clinical feasibility of HK-660S (beta-lapachone) in PSC.
Microglia and Gut Microbiota: A Double-Edged Sword in Alzheimer's Disease
Authors: Nargis Bano, Sameera Khan, Shakir Ahamad, Jitendra Singh Kanshana, Nawab John Dar, Sumbul Khan, Aamir Nazir, Shahnawaz Ali Bhat
Journal: Ageing Research Reviews (2024)