tbuckley/cabot-search huggingface dataset:
Restoration of cervical lymphatic vessel function in aging rescues cerebrospinal fluid drainage
Authors: Ting Du, Aditya Raghunandan, Humberto Mestre, Virginia Plá, Guojun Liu, Antonio Ladrón-de-Guevara, Evan Newbold, Paul Tobin, Daniel Gahn-Martinez, Saurav Pattanayak, Qinwen Huang, Weiguo Peng, Maiken Nedergaard, Douglas H. Kelley
Journal: Nature Aging (2024)
LIFR regulates cholesterol-driven bidirectional hepatocyte–neutrophil cross-talk to promote liver regeneration
Authors: Yalan Deng, Zilong Zhao, Marisela Sheldon, Yang Zhao, Hongqi Teng, Consuelo Martinez, Jie Zhang, Chunru Lin, Yutong Sun, Fan Yao, Michael A. Curran, Hao Zhu, Li Ma
Journal: Nature Metabolism (2024)
<i>Notes from the Field:</i> Heightened Precautions for Imported Dogs Vaccinated with Potentially Ineffective Rabies Vaccine — United States, August 2021−April 2024
Authors: Mark S. Freedman, Samantha D. Swisher, Ryan M. Wallace, Mark E. Laughlin, Clive M. Brown, Emily G. Pieracci
Journal: MMWR Morbidity and Mortality Weekly Report (2024)
Brain aging patterns in a large and diverse cohort of 49,482 individuals
Authors: Zhijian Yang, Junhao Wen, Guray Erus, Sindhuja T. Govindarajan, Randa Melhem, Elizabeth Mamourian, Yuhan Cui, Dhivya Srinivasan, Ahmed Abdulkadir, Paraskevi Parmpi, Katharina Wittfeld, Hans J. Grabe, Robin Bülow, Stefan Frenzel, Duygu Tosun, Murat Bilgel, Yang An, Dahyun Yi, Daniel S. Marcus, Pamela LaMontagne, Tammie L. S. Benzinger, Susan R. Heckbert, Thomas R. Austin, Shari R. Waldstein, Michele K. Evans, Alan B. Zonderman, Lenore J. Launer, Aristeidis Sotiras, Mark A. Espeland, Colin L. Masters, Paul Maruff, Jurgen Fripp, Arthur W. Toga, Sid O’Bryant, Mallar M. Chakravarty, Sylvia Villeneuve, Sterling C. Johnson, John C. Morris, Marilyn S. Albert, Kristine Yaffe, Henry Völzke, Luigi Ferrucci, R. Nick Bryan, Russell T. Shinohara, Yong Fan, Mohamad Habes, Paris Alexandros Lalousis, Nikolaos Koutsouleris, David A. Wolk, Susan M. Resnick, Haochang Shou, Ilya M. Nasrallah, Christos Davatzikos
Journal: Nature Medicine (2024)
Invasive Nontypeable <i>Haemophilus influenzae</i> Disease Outbreak at an Elementary School — Michigan, May 2023
Authors: Meghan M. Weinberg, Kaitlyn Akel, Oluwaseun Akinyemi, Thrishika Balasubramanian, Heather M. Blankenship, Jennifer P. Collins, Jim Collins, Tiffany Henderson, Shannon Johnson, Joyce Lai, Lucy A. McNamara, Claudia Richardson, Shalabh Sharma, Darsheen Sheth
Journal: MMWR Morbidity and Mortality Weekly Report (2024)

In May 2023, the Detroit Health Department was notified of four cases of invasive nontypeable Haemophilus influenzae (Hi) disease among students attending the same elementary school and grade, all with illness onsets within 7 days.Three patients were hospitalized, and one died.Most U.S. cases of invasive Hi disease are caused by nontypeable strains.No vaccines against nontypeable or non-type b Hi strains are currently available.Chemoprophylaxis is not typically recommended in response to nontypeable Hi cases; however, because of the high attack rate (four cases among 46 students; 8.7%), rifampin prophylaxis was recommended for household contacts of patients with confirmed cases and for all students and staff members in the school wing where confirmed cases occurred.Only 10.8% of students for whom chemoprophylaxis was recommended took it, highlighting gaps in understanding among caregivers and health care providers about persons for whom chemoprophylaxis was recommended.Public health authorities subsequently enhanced communication and education to the school community, improved coordination with health care partners, and established mass prophylaxis clinics at the school.This outbreak highlights the potential for nontypeable Hi to cause serious illness and outbreaks and the need for chemoprophylaxis guidance for nontypeable Hi disease.Achieving high chemoprophylaxis coverage requires education, communication, and coordination with community and health care partners.
Microparticle Mediated Delivery of Apelin Improves Heart Function in Post Myocardial Infarction Mice
Authors: Ling Tang, Huiliang Qiu, Bing Xu, Yajuan Su, Verah Nyarige, Pengsheng Li, Houjia Chen, Brady Killham, Jun Liao, Henderson Adam, Aaron Yang, Alexander Yu, Michelle Jang, Michael Rubart, Jingwei Xie, Wuqiang Zhu
Journal: Circulation Research (2024)

BACKGROUND: Apelin is an endogenous prepropeptide that regulates cardiac homeostasis and various physiological processes. Intravenous injection has been shown to improve cardiac contractility in patients with heart failure. However, its short half-life prevents studying its impact on left ventricular remodeling in the long term. Here, we aim to study whether microparticle-mediated slow release of apelin improves heart function and left ventricular remodeling in mice with myocardial infarction (MI). METHODS: A cardiac patch was fabricated by embedding apelin-containing microparticles in a fibrin gel scaffold. MI was induced via permanent ligation of the left anterior descending coronary artery in adult C57BL/6J mice followed by epicardial patch placement immediately after (acute MI) or 28 days (chronic MI) post-MI. Four groups were included in this study, namely sham, MI, MI plus empty microparticle-embedded patch treatment, and MI plus apelin-containing microparticle-embedded patch treatment. Cardiac function was assessed by transthoracic echocardiography. Cardiomyocyte morphology, apoptosis, and cardiac fibrosis were evaluated by histology. Cardioprotective pathways were determined by RNA sequencing, quantitative polymerase chain reaction, and Western blot. RESULTS: The level of endogenous apelin was largely reduced in the first 7 days after MI induction and it was normalized by day 28. Apelin-13 encapsulated in poly(lactic-co-glycolic acid) microparticles displayed a sustained release pattern for up to 28 days. Treatment with apelin-containing microparticle-embedded patch inhibited cardiac hypertrophy and reduced scar size in both acute and chronic MI models, which is associated with improved cardiac function. Data from cellular and molecular analyses showed that apelin inhibits the activation and proliferation of cardiac fibroblasts by preventing transforming growth factor-β–mediated activation of Smad2/3 (supporessor of mothers against decapentaplegic 2/3) and downstream profibrotic gene expression. CONCLUSIONS: Poly(lactic-co-glycolic acid) microparticles prolonged the apelin release time in the mouse hearts. Epicardial delivery of the apelin-containing microparticle-embedded patch protects mice from both acute and chronic MI-induced cardiac dysfunction, inhibits cardiac fibrosis, and improves left ventricular remodeling.
International Initiatives of the American Heart Association: Original Concepts, Present Programs, and Future Focus: A Science Advisory From the American Heart Association
Authors: Sidney C. Smith, Dhruv S. Kazi, Cheryl A.M. Anderson, Craig Beam, Douglas S. Boyle, Kelly Griesenbeck Carter, Mitchell S.V. Elkind, Pooja Khatri, John Meiners, Louise Morgan, Puja Patel, Melanie B. Turner, Nanette K. Wenger
Journal: Circulation (2024)

The American Heart Association (AHA), founded in 1924, is anchored in the core belief that scientific research can lead the way to better prevention, treatment, recovery, and ultimately a cure for cardiovascular disease. Historically, the association's involvement in international efforts centered on scientific cooperation. Activities mostly involved AHA leadership presenting at international scientific meetings and leaders from other countries sharing scientific and medical information at AHA meetings. Although the AHA's and American Stroke Association's international efforts have expanded substantially since those early days, global knowledge exchange remains the bedrock of its international endeavors. As the AHA turns 100, we reflect on the successful global efforts in prevention, resuscitation, global advocacy, quality improvement, and health equity that have guided the organization to a place of readiness for "advancing health and hope, for everyone, everywhere." Motivated by the enormous potential for population health gains in an aging world, the AHA is entering its second century with redoubled commitment to improving global cardiovascular and cerebrovascular health for all.
Precision prediction of heart failure events in patients with dilated cardiomyopathy and mildly reduced ejection fraction using multi‐parametric cardiovascular magnetic resonance
Authors: Daniel J. Hammersley, Srinjay Mukhopadhyay, Xiuyu Chen, Richard E. Jones, Aaraby Ragavan, Saad Javed, Husein Rajabali, Emmanuel Androulakis, Lara Curran, Lukas Mach, Zohya Khalique, Resham Baruah, Kaushik Guha, John Gregson, Shihua Zhao, Antonio De Marvao, Upasana Tayal, Amrit S. Lota, James S. Ware, Dudley J. Pennell, Sanjay K. Prasad, Brian P. Halliday
Journal: European Journal of Heart Failure (2024)

To assess whether left ventricular (LV) global longitudinal strain (GLS), derived from cardiovascular magnetic resonance (CMR), is associated with (i) progressive heart failure (HF), and (ii) sudden cardiac death (SCD) in patients with dilated cardiomyopathy with mildly reduced ejection fraction (DCMmrEF).
Correction: Ovarian Cancers Harbor Defects in Nonhomologous End Joining Resulting in Resistance to Rucaparib
Authors: Aiste McCormick, Peter Donoghue, Michelle Dixon, Richard O’Sullivan, Rachel L. O’Donnell, James Murray, Angelika Kaufmann, Nicola J. Curtin, Richard J. Edmondson
Journal: Clinical Cancer Research (2024)
Editor’s Note: Detection of Wilms’ Tumor Antigen–Specific CTL in Tumor-Draining Lymph Nodes of Patients with Early Breast Cancer
Authors: Roopinder Gillmore, Shao-An Xue, Angelika Holler, Jaspal Kaeda, Dimitri Hadjiminas, Vourneen Healy, Roberto Dina, Suzanne C. Parry, Ilaria Bellantuono, Yasmeen Ghani, R. Charles Coombes, Jonathan Waxman, Hans J. Stauss
Journal: Clinical Cancer Research (2024)
Editor’s Note: 4E-Binding Protein 1, a Cell Signaling Hallmark in Breast Cancer That Correlates with Pathologic Grade and Prognosis
Authors: Federico Rojo, Laura Najera, José Lirola, José Jiménez, Marta Guzmán, M. Dolors Sabadell, Jose Baselga, Santiago Ramon y Cajal
Journal: Clinical Cancer Research (2024)
Dose–response relationship between computerized cognitive training and cognitive improvement
Authors: Liyang Liu, Haibo Wang, Yi Xing, Ziheng Zhang, Qingge Zhang, Ming Dong, Zhujiang Ma, Longjun Cai, Xiaoyi Wang, Yi Tang
Journal: npj Digital Medicine (2024)

Although computerized cognitive training (CCT) is an effective digital intervention for cognitive impairment, its dose-response relationship is understudied. This retrospective cohort study explores the association between training dose and cognitive improvement to find the optimal CCT dose. From 2017 to 2022, 8,709 participants with subjective cognitive decline, mild cognitive impairment, and mild dementia were analyzed. CCT exposure varied in daily dose and frequency, with cognitive improvement measured weekly using Cognitive Index. A mixed-effects model revealed significant Cognitive Index increases across most dose groups before reaching the optimal dose. For participants under 60 years, the optimal dose was 25 to <30 min per day for 6 days a week. For those 60 years or older, it was 50 to <55 min per day for 6 days a week. These findings highlight a dose-dependent effect in CCT, suggesting age-specific optimal dosing for cognitive improvement.
An Immunometabolic Route for Activating cGAS/STING to Drive Anticancer Immunity
Authors: Francisca Borges, Abhishek D. Garg
Journal: Cancer Research (2024)

The cGAS/STING pathway is a crucial immune activator in cancer biology, triggering innate immunosurveillance against tumors by sensing and reacting to endogenous mitochondrial DNA (mtDNA). In this issue of Cancer Research, research by Saha and colleagues highlights the significant impact of serine deprivation on this pathway, thereby unveiling its potential for anticancer therapy. Serine is essential for cellular metabolism and influences tumor growth and immune responses. Depriving cells of serine caused mitochondrial dysfunction and the release of mtDNA into the cytosol, activating the cGAS/STING pathway and inducing type I IFN responses. In mouse models, serine deprivation enhanced antitumor immunity, with increased tumoral immune infiltration, including CD4+/CD8+ T cells and type I IFN responses. Clinically, a genetic signature indicative of lower serine enrichment in colorectal cancer patients correlated with immune activation and improved survival. Furthermore, combining serine deprivation with PD1 blockade significantly reduced tumor volume and led to long-term immunity in mice, suggesting that serine depletion enhances the efficacy of immune checkpoint blockade. These findings propose serine deprivation as a promising strategy to boost antitumor immunity and improve cancer patient outcomes. See related article by Saha et al., p. 2645
Oncogenic <i>SLC2A11–MIF</i> fusion protein interacts with polypyrimidine tract binding protein 1 to facilitate bladder cancer proliferation and metastasis by regulating mRNA stability
Authors: Liang Cheng, Chenwei Yang, Junlin Lu, Ming Huang, Ruihui Xie, Sarah Lynch, Justin Elfman, Yuhang Huang, Sen Liu, Siting Chen, Baoqing He, Tianxin Lin, Hui Li, Xu Chen, Jian Huang
Journal: MedComm (2024)

Chimeric RNAs, distinct from DNA gene fusions, have emerged as promising therapeutic targets with diverse functions in cancer treatment. However, the functional significance and therapeutic potential of most chimeric RNAs remain unclear. Here we identify a novel fusion transcript of solute carrier family 2-member 11 (
Analysis across Taiwan Biobank, Biobank Japan, and UK Biobank identifies hundreds of novel loci for 36 quantitative traits
Authors: Chia-Yen Chen, Tzu-Ting Chen, Yen-Chen Anne Feng, Mingrui Yu, Shu-Chin Lin, Ryan J. Longchamps, Shi-Heng Wang, Yi-Hsiang Hsu, Hwai-I. Yang, Po-Hsiu Kuo, Mark J. Daly, Wei J. Chen, Hailiang Huang, Tian Ge, Yen-Feng Lin
Journal: Cell Genomics (2024)
First-line Systemic Therapy Following Adjuvant Immunotherapy in Renal Cell Carcinoma: An International Multicenter Study
Authors: Talal El Zarif, Karl Semaan, Wanling Xie, Marc Eid, Martin Zarba, Wadih Issa, Tian Zhang, Charles B Nguyen, Ajjai Alva, Catherine C Fahey, Kathryn E Beckermann, Jose A Karam, Matthew T Campbell, Giuseppe Procopio, Marco Stellato, Sebastiano Buti, Anezka Zemankova, Bohuslav Melichar, Francesco Massari, Veronica Mollica, Balaji Venugopal, Hedyeh Ebrahimi, Guillermo de Velasco, Howard Paul Gurney, Ugo De Giorgi, Omi Parikh, Eric Winquist, Viraj Master, Abraham Ruiz Garcia, Hernan Javier Cutuli, Thomas Robert Ferguson, Marine Gross-Goupil, Sylvan C Baca, Sumanta K Pal, David A Braun, Rana R McKay, Daniel Y C Heng, Toni K Choueiri
Journal: European Urology (2024)
Robust automated calcification meshing for personalized cardiovascular biomechanics
Authors: Daniel H. Pak, Minliang Liu, Theodore Kim, Caglar Ozturk, Raymond McKay, Ellen T. Roche, Rudolph Gleason, James S. Duncan
Journal: npj Digital Medicine (2024)

Calcification has significant influence over cardiovascular diseases and interventions. Detailed characterization of calcification is thus desired for predictive modeling, but calcium deposits on cardiovascular structures are still often manually reconstructed for physics-driven simulations. This poses a major bottleneck for large-scale adoption of computational simulations for research or clinical use. To address this, we propose an end-to-end automated image-to-mesh algorithm that enables robust incorporation of patient-specific calcification onto a given cardiovascular tissue mesh. The algorithm provides a substantial speed-up from several hours of manual meshing to ~1 min of automated computation, and it solves an important problem that cannot be addressed with recent template-based meshing techniques. We validated our final calcified tissue meshes with extensive simulations, demonstrating our ability to accurately model patient-specific aortic stenosis and Transcatheter Aortic Valve Replacement. Our method may serve as an important tool for accelerating the development and usage of personalized cardiovascular biomechanics.
Caspase-11 mediated inflammasome activation in macrophages by systemic infection of A. actinomycetemcomitans exacerbates arthritis
Authors: Tokuju Okano, Hiroshi Ashida, Noriko Komatsu, Masayuki Tsukasaki, Tamako Iida, Marie Iwasawa, Yuto Takahashi, Yasuo Takeuchi, Takanori Iwata, Miwa Sasai, Masahiro Yamamoto, Hiroshi Takayanagi, Toshihiko Suzuki
Journal: International Journal of Oral Science (2024)

Abstract Clinical studies have shown that Aggregatibacter actinomycetemcomitans ( A. actinomycetemcomitans ) is associated with aggressive periodontitis and can potentially trigger or exacerbate rheumatoid arthritis (RA). However, the mechanism is poorly understood. Here, we show that systemic infection with A. actinomycetemcomitans triggers the progression of arthritis in mice anti-collagen antibody-induced arthritis (CAIA) model following IL-1β secretion and cell infiltration in paws in a manner that is dependent on caspase-11-mediated inflammasome activation in macrophages. The administration of polymyxin B (PMB), chloroquine, and anti-CD11b antibody suppressed inflammasome activation in macrophages and arthritis in mice, suggesting that the recognition of lipopolysaccharide (LPS) in the cytosol after bacterial degradation by lysosomes and invasion via CD11b are needed to trigger arthritis following inflammasome activation in macrophages. These data reveal that the inhibition of caspase-11-mediated inflammasome activation potentiates aggravation of RA induced by infection with A. actinomycetemcomitans . This work highlights how RA can be progressed by inflammasome activation as a result of periodontitis-associated bacterial infection and discusses the mechanism of inflammasome activation in response to infection with A . actinomycetemcomitans .
Mussel-inspired sulfated hyaluronan cryogel patch with antioxidant, anti-inflammatory, and drug-loading properties for multifunctional wound adhesives
Authors: Wonmoon Song, Young Hwan Choi, Young Gi Moon, Changyub Lee, M Nivedhitha Sundaram, Nathaniel S Hwang
Journal: Bioactive Materials (2024)

Wounds, characterized by the disruption of the continuity of body tissues resulting from external trauma, manifest in diverse types and locations. Although numerous wound dressings are available for various wound scenarios, it remains challenging to find an integrative wound dressing capable of addressing diverse wound situations. We focused on utilizing sulfated hyaluronan (sHA), known for its anti-inflammatory properties and capacity to load cationic drugs. By conjugating catechol groups to sHA (sHA-CA), we achieved several advantages in wound healing: 1) Fabrication of patches through crosslinking with catechol-modified high-molecular-weight hyaluronan (HA(HMW)-CA), 2) Adhesiveness that enabled stable localization, 3) Radical scavenging that could synergize with the immunomodulation of sHA. The sHA-CA patches demonstrated therapeutic efficacy in three distinct murine wound models: diabetic wound, hepatic hemorrhage, and post-surgical adhesion. Collectively, these findings underscore the potential of the sHA-CA patch as a promising candidate for the next-generation wound dressing.
Oxygen-enhanced MRI detects incidence, onset and heterogeneity of radiation-induced hypoxia modification in HPV-associated oropharyngeal cancer
Authors: Michael J. Dubec, James Price, Michael Berks, John Gaffney, Ross A. Little, Nuria Porta, Nivetha Sridharan, Anubhav Datta, Damien J. McHugh, Christina J. Hague, Susan Cheung, Prakash Manoharan, Marcel van Herk, Ananya Choudhury, Julian C. Matthews, Geoff J.M. Parker, David L. Buckley, Kevin J. Harrington, Andrew McPartlin, James P.B. O’Connor
Journal: Clinical Cancer Research (2024)

Abstract Purpose: Hypoxia mediates treatment resistance in solid tumors. We evaluated if oxygen-enhanced MRI–derived hypoxic volume (HVMRI) is repeatable and can detect radiotherapy-induced hypoxia modification in human papillomavirus–associated oropharyngeal head and neck squamous cell cancer. Experimental Design: A total of 27 patients were recruited prospectively between March 2021 and January 2024. HVMRI was measured in primary and nodal tumors prior to standard-of-care (chemo)radiotherapy and then at weeks 2 and 4 (W2 and W4) into therapy. Two pretreatment scans assessed biomarker within-subject coefficient of variation and repeatability coefficient (RC). Cohort treatment response was measured using mixed-effects modeling. Responding lesions were identified by comparing HVMRI change with RC limits of agreement. Results: Oxygen-enhanced MRI identified hypoxia in all lesions. The HVMRI within-subject coefficient of variation was 24.6%, and RC limits of agreement were −45.7% to 84.1%. A cohort median pretreatment HVMRI of 11.3 cm3 reduced to 6.9 cm3 at W2 and 5.9 cm3 at W4 (both P &amp;lt; 0.001). HVMRI was reduced in 54.5% of individual lesions by W2 and in 88.2% by W4. All lesions with W2 hypoxia reduction showed persistent modification at W4. HVMRI reduced in some lesions that showed no overall volume change. Hypoxia modification was discordant between primary and nodal tumors in 50.0% of patients. Conclusions: Radiation-induced hypoxia modification can occur as early as W2, but onset varies between patients and was not necessarily associated with overall size change. Half of all patients had discordant changes in primary and nodal tumors. These findings have implications for patient selection and timing of dose de-escalation strategies in human papillomavirus–associated oropharyngeal carcinoma.
Genome-wide Studies Reveal Genetic Risk Factors for Hepatic Fat Content
Authors: Yanni Li, Eline H van den Berg, Alexander Kurilshikov, Dasha V Zhernakova, Ranko Gacesa, Shixian Hu, Esteban A Lopera-Maya, Alexandra Zhernakova, Raul Aguirre-Gamboa, Patrick Deelen, Lude Franke, Jan A Kuivenhoven, Esteban A Lopera-Maya, Ilja M Nolte, Serena Sanna, Harold Snieder, Morris A Swertz, Peter M Visscher, Judith M Vonk, Cisca Wijmenga, Vincent E de Meijer, Serena Sanna, Robin P F Dullaart, Hans Blokzijl, Eleonora A M Festen, Jingyuan Fu, Rinse K Weersma
Journal: Genomics Proteomics & Bioinformatics (2024)

Abstract Genetic susceptibility to metabolic associated fatty liver disease (MAFLD) is complex and poorly characterized. Accurate characterization of the genetic background of hepatic fat content would provide insights into disease etiology and causality of risk factors. We performed genome-wide association study (GWAS) on two noninvasive definitions of hepatic fat content: magnetic resonance imaging proton density fat fraction (MRI-PDFF) in 16,050 participants and fatty liver index (FLI) in 388,701 participants from the United Kingdom (UK) Biobank (UKBB). Heritability, genetic overlap, and similarity between hepatic fat content phenotypes were analyzed, and replicated in 10,398 participants from the University Medical Center Groningen (UMCG) Genetics Lifelines Initiative (UGLI). Meta-analysis of GWASs of MRI-PDFF in UKBB revealed five statistically significant loci, including two novel genomic loci harboring CREB3L1 (rs72910057-T, P = 5.40E−09) and GCM1 (rs1491489378-T, P = 3.16E−09), respectively, as well as three previously reported loci: PNPLA3, TM6SF2, and APOE. GWAS of FLI in UKBB identified 196 genome-wide significant loci, of which 49 were replicated in UGLI, with top signals in ZPR1 (P = 3.35E−13) and FTO (P = 2.11E−09). Statistically significant genetic correlation (rg) between MRI-PDFF (UKBB) and FLI (UGLI) GWAS results was found (rg = 0.5276, P = 1.45E−03). Novel MRI-PDFF genetic signals (CREB3L1 and GCM1) were replicated in the FLI GWAS. We identified two novel genes for MRI-PDFF and 49 replicable loci for FLI. Despite a difference in hepatic fat content assessment between MRI-PDFF and FLI, a substantial similar genetic architecture was found. FLI is identified as an easy and reliable approach to study hepatic fat content at the population level.