tbuckley/cabot-search huggingface dataset:
Directional Endothelial Communication by Polarized Extracellular Vesicle Release
Authors: Sneha Raju, Steven R. Botts, Mark C. Blaser, Majed Abdul-Samad, Kamalben Prajapati, Negar Khosraviani, Tse Wing Winnie Ho, Leandro C.D. Breda, Crizza Ching, Natalie J. Galant, Lindsey Fiddes, Ruilin Wu, Cassandra L. Clift, Tan Pham, Warren L. Lee, Sasha A. Singh, Elena Aikawa, Jason E. Fish, Kathryn L. Howe
Journal: Circulation Research (2024)

Extracellular vesicles (EVs) contain bioactive cargo including miRNAs and proteins that are released by cells during cell-cell communication. Endothelial cells (ECs) form the innermost lining of all blood vessels, interfacing with cells in the circulation and vascular wall. It is unknown whether ECs release EVs capable of governing recipient cells within these 2 separate compartments. Given their boundary location, we propose ECs use bidirectional release of distinct EV cargo in quiescent (healthy) and activated (atheroprone) states to communicate with cells within the circulation and blood vessel wall.
Elucidating the role of diet in maintaining gut health to reduce the risk of obesity, cardiovascular and other age-related inflammatory diseases: recent challenges and future recommendations
Authors: Tariq Aziz, Nageen Hussain, Zunaira Hameed, Lin Lin
Journal: Gut Microbes (2024)

A healthy balanced diet is crucial in protecting the immune system against infections and diseases. Poor diets, such as the Western diet, contribute to the development of metabolic diseases, hypertension, and obesity. Microbiota, primarily composed of different microorganisms and residing in the gastrointestinal tract (GIT), also play a significant role in maintaining gut health. Polyphenols and probiotics found in fruits, vegetables, whole grains, legumes, nuts, and seeds promote gut health and support the growth of beneficial bacteria. Different types of diets, their categories, and their impact on health are also mentioned. The relationship between diet, gut health, and the risk of developing obesity, cardiovascular diseases, and inflammatory diseases is discussed in this review article. The rationale behind the review concludes future recommendations for maintaining gut health and reducing the occurrence of obesity, cardiometabolic diseases, and other inflammatory diseases. There is also the need for standardized research methods, long-term studies, and translating scientific knowledge into practical dietary recommendations.
Retraction notice to “Viability and proliferation of rat MSCs on adhesion protein-modified PET and PU scaffolds” [Biomaterials 33/12 (2012) 8094–8103]
Authors: Ylva Gustafsson, Johannes Haag, Philipp Jungebluth, Vanessa Lundin, Mei Ling Lim, Silvia Baiguera, Fatemeh Ajalloueian, Costantino Del Gaudio, Alessandra Bianco, Guido Moll, Sebastian Sjöqvist, Greg Lemon, Ana Isabel Teixeira, Paolo Macchiarini
Journal: Biomaterials (2024)
Interpreting and integrating genomic tests results in clinical cancer care: Overview and practical guidance
Authors: Raffaella Casolino, Philip A. Beer, Debyani Chakravarty, Melissa B. Davis, Umberto Malapelle, Luca Mazzarella, Nicola Normanno, Chantal Pauli, Vivek Subbiah, Clare Turnbull, C. Benedikt Westphalen, Andrew V. Biankin
Journal: CA A Cancer Journal for Clinicians (2024)

Abstract The last decade has seen rapid progress in the use of genomic tests, including gene panels, whole‐exome sequencing, and whole‐genome sequencing, in research and clinical cancer care. These advances have created expansive opportunities to characterize the molecular attributes of cancer, revealing a subset of cancer‐associated aberrations called driver mutations . The identification of these driver mutations can unearth vulnerabilities of cancer cells to targeted therapeutics, which has led to the development and approval of novel diagnostics and personalized interventions in various malignancies. The applications of this modern approach, often referred to as precision oncology or precision cancer medicine , are already becoming a staple in cancer care and will expand exponentially over the coming years. Although genomic tests can lead to better outcomes by informing cancer risk, prognosis, and therapeutic selection, they remain underutilized in routine cancer care. A contributing factor is a lack of understanding of their clinical utility and the difficulty of results interpretation by the broad oncology community. Practical guidelines on how to interpret and integrate genomic information in the clinical setting, addressed to clinicians without expertise in cancer genomics, are currently limited. Building upon the genomic foundations of cancer and the concept of precision oncology, the authors have developed practical guidance to aid the interpretation of genomic test results that help inform clinical decision making for patients with cancer. They also discuss the challenges that prevent the wider implementation of precision oncology.
Autophagy protein ATG-16.2 and its WD40 domain mediate the beneficial effects of inhibiting early-acting autophagy genes in C. elegans neurons
Authors: Yongzhi Yang, Meghan Lee Arnold, Caitlin M. Lange, Ling-Hsuan Sun, Michael Broussalian, Saam Doroodian, Hiroshi Ebata, Elizabeth H. Choy, Karie Poon, Tatiana M. Moreno, Anupama Singh, Monica Driscoll, Caroline Kumsta, Malene Hansen
Journal: Nature Aging (2024)
Platelet Membrane‐Encapsulated Nanocomplexes Based on Profundity Scavenging ROS Strategy for Myocardial Infarction Therapy
Authors: Meng Sun, Nan Hu, Yangyang Gao, Nan Lv, Xiaohong Fu, Yafeng Li, Shaodong Zhai, Ruiping Zhang
Journal: Advanced Healthcare Materials (2024)

Ischemia-induced myocardial injury has become a serious threat to human health, and its treatment remains a challenge. The occurrence of ischemic events leads to a burst release of reactive oxygen species (ROS), which triggers extensive oxidative damage and leads to dysfunctional autophagy, making it difficult for cells to maintain homeostasis. Antioxidants and modulation of autophagy have thus become promising strategies for the treatment of ischemic myocardial injury. This study proposes an antioxidant-activated autophagy therapeutic regimen based on combining melanin (Mel), an excellent antioxidant with metformin mimetic ploymetformin via electrostatic interactions, to obtain a nanocomplex (Met-Mel). The nanocomplex is finally encapsulated with platelet membranes (PMN) to construct a biomimetic nanoparticle (PMN@Met-Mel) capable of targeting injured myocardium. The prepared PMN@Met-Mel has good Mel loading capacity and optimal biosafety. It exhibits excellent antioxidant activity and autophagy activation, rapidly restoring mitochondrial function. Moreover, RNA sequencing (RNA-seq) analysis reveals that PMN@Met-Mel operates mechanistically by triggering the activation of the autophagy pathway. Subsequent in vivo experiments showcase promising cardioprotective effects of these nanoparticles. These discoveries present a newly devised nanoplatform with promising potential for the effective treatment of myocardial infarction.
Somatic mouse models of gastric cancer reveal genotype-specific features of metastatic disease
Authors: Josef Leibold, Kaloyan M. Tsanov, Corina Amor, Yu-Jui Ho, Francisco J. Sánchez-Rivera, Judith Feucht, Timour Baslan, Hsuan-An Chen, Sha Tian, Janelle Simon, Alexandra Wuest, John E. Wilkinson, Scott W. Lowe
Journal: Nature Cancer (2024)

Abstract Metastatic gastric carcinoma is a highly lethal cancer that responds poorly to conventional and molecularly targeted therapies. Despite its clinical relevance, the mechanisms underlying the behavior and therapeutic response of this disease are poorly understood owing, in part, to a paucity of tractable models. Here we developed methods to somatically introduce different oncogenic lesions directly into the murine gastric epithelium. Genotypic configurations observed in patients produced metastatic gastric cancers that recapitulated the histological, molecular and clinical features of all nonviral molecular subtypes of the human disease. Applying this platform to both wild-type and immunodeficient mice revealed previously unappreciated links between the genotype, organotropism and immune surveillance of metastatic cells, which produced distinct patterns of metastasis that were mirrored in patients. Our results establish a highly portable platform for generating autochthonous cancer models with flexible genotypes and host backgrounds, which can unravel mechanisms of gastric tumorigenesis or test new therapeutic concepts.
Antimalarial artesunate–mefloquine versus praziquantel in African children with schistosomiasis: an open-label, randomized controlled trial
Authors: Emmanuel Bottieau, Moustapha Mbow, Isabel Brosius, Clémentine Roucher, Cheikh Tidiane Gueye, Ousmane Thiam Mbodj, Babacar Thiendella Faye, Annelies De Hondt, Bart Smekens, Diana Arango, Christophe Burm, Achilleas Tsoumanis, Linda Paredis, Yven Van Herrewege, Idzi Potters, Joachim Richter, Anna Rosanas-Urgell, Badara Cissé, Souleymane Mboup, Katja Polman
Journal: Nature Medicine (2024)

Abstract Schistosomiasis treatment entirely relies on a single drug, praziquantel, prompting research into alternative therapeutics. Here we evaluated the efficacy and safety of the antimalarial combination artesunate–mefloquine for the treatment of schistosomiasis in a proof-of-concept, pragmatic, open-label, randomized controlled trial in primary schools of six villages endemic for schistosomiasis in northern Senegal. Children (6–14 years) were eligible if Schistosoma eggs were detected by microscopy in urine and/or stool. In total, 726 children were randomized 1:1 to praziquantel (standard care: 40 mg kg −1 single dose; n = 364) or to artesunate–mefloquine (antimalarial dosage: artesunate 4 mg kg −1 and mefloquine 8 mg kg −1 daily for three consecutive days; n = 362). Eight children not meeting the inclusion criteria were excluded from efficacy analysis. Median age of the remaining 718 participants was 9 years; 399 (55.6%) were male, and 319 (44.4%) female; 99.3% were infected with Schistosoma haematobium and 15.2% with S. mansoni . Primary outcomes were cure rate, assessed by microscopy, and frequency of drug-related adverse effects of artesunate–mefloquine versus praziquantel at 4 weeks after treatment. Cure rate was 59.6% (208/349) in the artesunate–mefloquine arm versus 62.1% (211/340) in the praziquantel arm. The difference of −2.5% (95% confidence interval (CI) −9.8 to 4.8) met the predefined criteria of noninferiority (margin set at 10%). All drug-related adverse events were mild or moderate, and reported in 28/361 children receiving artesunate–mefloquine (7.8%; 95% CI 5.4 to 11.0) versus 8/363 (2.2%; 95% CI 1.1 to 4.3) receiving praziquantel ( P &lt; 0.001). Artesunate–mefloquine at antimalarial dosage was moderately safe and noninferior to standard-care praziquantel for the treatment of schistosomiasis, predominantly due to S. haematobium . Multicentric trials in different populations and epidemiological settings are needed to confirm these findings. ClinicalTrials.gov identifier: NCT03893097 .
Multi-ancestry genome-wide association study of major depression aids locus discovery, fine mapping, gene prioritization and causal inference
Authors: Xiangrui Meng, Georgina Navoly, Olga Giannakopoulou, Daniel F Levey, Dora Koller, Gita A Pathak, Nastassja Koen, Kuang Lin, Mark J Adams, Miguel E Rentería, Yanzhe Feng, J Michael Gaziano, Dan J Stein, Heather J Zar, Megan L Campbell, David A van Heel, Bhavi Trivedi, Sarah Finer, Andrew McQuillin, Nick Bass, V Kartik Chundru, Hilary C Martin, Qin Qin Huang, Maria Valkovskaya, Chia-Yi Chu, Susan Kanjira, Po-Hsiu Kuo, Hsi-Chung Chen, Shih-Jen Tsai, Yu-Li Liu, Kenneth S Kendler, Roseann E Peterson, Na Cai, Yu Fang, Srijan Sen, Laura J Scott, Margit Burmeister, Ruth J F Loos, Michael H Preuss, Ky'Era V Actkins, Lea K Davis, Monica Uddin, Agaz H Wani, Derek E Wildman, Allison E Aiello, Robert J Ursano, Ronald C Kessler, Masahiro Kanai, Yukinori Okada, Saori Sakaue, Jill A Rabinowitz, Brion S Maher, George Uhl, William Eaton, Carlos S Cruz-Fuentes, Gabriela A Martinez-Levy, Adrian I Campos, Iona Y Millwood, Zhengming Chen, Liming Li, Sylvia Wassertheil-Smoller, Yunxuan Jiang, Chao Tian, Nicholas G Martin, Brittany L Mitchell, Enda M Byrne, Swapnil Awasthi, Jonathan R I Coleman, Stephan Ripke, Tamar Sofer, Robin G Walters, Andrew M McIntosh, Renato Polimanti, Erin C Dunn, Murray B Stein, Joel Gelernter, Cathryn M Lewis, Karoline Kuchenbaecker
Journal: Nature Genetics (2024)

Abstract Most genome-wide association studies (GWAS) of major depression (MD) have been conducted in samples of European ancestry. Here we report a multi-ancestry GWAS of MD, adding data from 21 cohorts with 88,316 MD cases and 902,757 controls to previously reported data. This analysis used a range of measures to define MD and included samples of African (36% of effective sample size), East Asian (26%) and South Asian (6%) ancestry and Hispanic/Latin American participants (32%). The multi-ancestry GWAS identified 53 significantly associated novel loci. For loci from GWAS in European ancestry samples, fewer than expected were transferable to other ancestry groups. Fine mapping benefited from additional sample diversity. A transcriptome-wide association study identified 205 significantly associated novel genes. These findings suggest that, for MD, increasing ancestral and global diversity in genetic studies may be particularly important to ensure discovery of core genes and inform about transferability of findings.
Biologic survival: a novel approach for drug efficacy estimation in psoriasis
Authors: Qinmengge Li, Lam C Tsoi
Journal: British Journal of Dermatology (2024)

Journal Article Corrected proof Biologic survival: a novel approach for drug efficacy estimation in psoriasis Get access Qinmengge Li, Qinmengge Li Writing - original draft, Writing - review & editing Department of Dermatology, Ann Arbor, MI, USADepartment of Biostatistics, Ann Arbor, MI, USA Search for other works by this author on: Oxford Academic Google Scholar Lam C Tsoi Lam C Tsoi Supervision, Writing - review & editing Department of Dermatology, Ann Arbor, MI, USADepartment of Biostatistics, Ann Arbor, MI, USADepartment of Computational Medicine and Bioinformatics, Mary H. Weiser Food Allergy Center, University of Michigan, Ann Arbor, MI, USA Correspondence: Lam C. Tsoi. Email: alextsoi@med.umich.edu https://orcid.org/0000-0003-1627-5722 Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, ljae007, https://doi.org/10.1093/bjd/ljae007 Published: 04 January 2024 Article history Received: 26 December 2023 Accepted: 31 December 2023 Published: 04 January 2024 Corrected and typeset: 25 January 2024
Belantamab mafodotin, pomalidomide and dexamethasone in refractory multiple myeloma: a phase 1/2 trial
Authors: Suzanne Trudel, Arleigh McCurdy, Martha L. Louzada, Stephen Parkin, Darrell White, Michael P. Chu, Rami Kotb, Hira Mian, Ibraheem Othman, Jiandong Su, Aniba Khan, Engin Gul, Donna Reece
Journal: Nature Medicine (2024)

Abstract Due to evolving treatment standards for newly diagnosed multiple myeloma, many patients will be triple-class exposed after initial relapses and have poor survival. Novel therapies and combinations are therefore required to improve outcomes. B cell maturation antigen (BCMA)-targeted biologics have emerged as an important new area of therapeutics for relapsed multiple myeloma. The two-part ALGONQUIN trial evaluated various doses and schedules of the anti-BCMA antibody–drug conjugate belantamab mafodotin plus pomalidomide and dexamethasone for patients who are lenalidomide refractory and proteosome inhibitor exposed. The primary endpoints, including evaluating dose-limiting toxicities, establishing the recommended Part 2 dose (RP2D) and overall response rate for patients treated at the RP2D, were met. Secondary efficacy endpoints included progression-free survival and overall survival. Patients treated on study ( N = 87) had a median of three previous regimens and 55.2% were triple-class refractory. At the RP2D the most common adverse events were decrease in best-corrected visual acuity (71.1%), keratopathy (65.8%), fatigue (57.9%), infection (47.4%; 7.9% grade ≥3), neutropenia (39.5%) and thrombocytopenia (39.5%). For RP2D patients ( n = 38), the overall response rate was 85.3%, ≥very good partial response 75.7% and estimated two-year progression-free survival 52.8% (95% confidence interval, 33.9% to 82.4%), at a median follow-up of 13.9 months. The RP2D schedule was associated with manageable antibody–drug conjugate-associated corneal adverse events and improved tolerability without compromising efficacy. Belantamab mafodotin plus pomalidomide and dexamethasone induced durable responses with promising overall survival in relapsed multiple myeloma, the results of which are yet to be confirmed in the phase 3 DREAMM-8 study. ClinicalTrials.gov Identifier: NCT03715478 .
Exome sequencing identifies genes associated with sleep-related traits
Authors: Chen-Jie Fei, Ze-Yu Li, Jing Ning, Liu Yang, Bang-Sheng Wu, Ju-Jiao Kang, Wei-Shi Liu, Xiao-Yu He, Jia You, Shi-Dong Chen, Huan Yu, Zhi-Li Huang, Jian-Feng Feng, Jin-Tai Yu, Wei Cheng
Journal: Nature Human Behaviour (2024)
Carnosine regulation of intracellular pH homeostasis promotes lysosome-dependent tumor immunoevasion
Authors: Ronghui Yan, Pinggen Zhang, Shengqi Shen, Yu Zeng, Ting Wang, Zhaolin Chen, Wenhao Ma, Junru Feng, Caixia Suo, Tong Zhang, Haoran Wei, Zetan Jiang, Rui Chen, Shi-ting Li, Xiuying Zhong, Weidong Jia, Linchong Sun, Chunlei Cang, Huafeng Zhang, Ping Gao
Journal: Nature Immunology (2024)
<i>Notes from the Field</i>: Supply Interruptions of First- and Second-Line Oral Drugs to Treat Tuberculosis During the Previous 12 Months — California, January–March, 2023
Authors: Scott A. Nabity, Rocio Agraz-Lara, Angelito Bravo, Robert Benjamin, Vanessa Fong, C. Kin Lam, Chris Keh, Sundari Mase, Jennifer Flood
Journal: MMWR Morbidity and Mortality Weekly Report (2024)
A deep learning system for predicting time to progression of diabetic retinopathy
Authors: Ling Dai, Bin Sheng, Tingli Chen, Qiang Wu, Ruhan Liu, Chun Cai, Liang Wu, Dawei Yang, Haslina Hamzah, Yuexing Liu, Xiangning Wang, Zhouyu Guan, Shujie Yu, Tingyao Li, Ziqi Tang, Anran Ran, Haoxuan Che, Hao Chen, Yingfeng Zheng, Jia Shu, Shan Huang, Chan Wu, Shiqun Lin, Dan Liu, Jiajia Li, Zheyuan Wang, Ziyao Meng, Jie Shen, Xuhong Hou, Chenxin Deng, Lei Ruan, Feng Lu, Miaoli Chee, Ten Cheer Quek, Ramyaa Srinivasan, Rajiv Raman, Xiaodong Sun, Ya Xing Wang, Jiarui Wu, Hai Jin, Rongping Dai, Dinggang Shen, Xiaokang Yang, Minyi Guo, Cuntai Zhang, Carol Y. Cheung, Gavin Siew Wei Tan, Yih-Chung Tham, Ching-Yu Cheng, Huating Li, Tien Yin Wong, Weiping Jia
Journal: Nature Medicine (2024)

Abstract Diabetic retinopathy (DR) is the leading cause of preventable blindness worldwide. The risk of DR progression is highly variable among different individuals, making it difficult to predict risk and personalize screening intervals. We developed and validated a deep learning system (DeepDR Plus) to predict time to DR progression within 5 years solely from fundus images. First, we used 717,308 fundus images from 179,327 participants with diabetes to pretrain the system. Subsequently, we trained and validated the system with a multiethnic dataset comprising 118,868 images from 29,868 participants with diabetes. For predicting time to DR progression, the system achieved concordance indexes of 0.754–0.846 and integrated Brier scores of 0.153–0.241 for all times up to 5 years. Furthermore, we validated the system in real-world cohorts of participants with diabetes. The integration with clinical workflow could potentially extend the mean screening interval from 12 months to 31.97 months, and the percentage of participants recommended to be screened at 1–5 years was 30.62%, 20.00%, 19.63%, 11.85% and 17.89%, respectively, while delayed detection of progression to vision-threatening DR was 0.18%. Altogether, the DeepDR Plus system could predict individualized risk and time to DR progression over 5 years, potentially allowing personalized screening intervals.
Corrigendum to “SIRT5 rs12216101 T&gt;G variant is associated with liver damage and mitochondrial dysfunction in patients with non-alcoholic fatty liver disease” [J Hepatol 80 (2024) 10-19]
Authors: Federico Salomone, Rosaria Maria Pipitone, Miriam Longo, Francesco Malvestiti, Angela Maria Amorini, Alfio Distefano, Elia Casirati, Ester Ciociola, Nunzio Iraci, Loredana Leggio, Rossella Zito, Nunzio Vicario, Concetta Saoca, Ville Männistö, Jussi Pihlajamäki, Sami Qadri, Hannele Yki-Järvinen, Stefano Romeo, Grazia Pennisi, Daniela Cabibi, Giuseppe Lazzarino, Anna Ludovica Fracanzani, Paola Dongiovanni, Luca Valenti, Salvatore Petta, Giovanni Li Volti, Stefania Grimaudo
Journal: Journal of Hepatology (2024)
Traditional Scraping (Gua Sha) Combined with Copper‐Curcumin Nanoparticle Oleogel for Accurate and Multi‐Effective Therapy of Androgenic Alopecia
Authors: Jie Gao, Zhenzhen Weng, Ze Zhang, Yuanyuan Liu, Zikang Liu, Xinyue Pu, Simin Yu, Yanhua Zhong, Danmeng Bai, Hongbo Xin, Xiaolei Wang
Journal: Advanced Healthcare Materials (2024)

Androgenetic alopecia (AGA) is a prevalent systemic disease caused by diverse factors, for which effective treatments are currently limited. Herein, the oleogel (OG) containing copper-curcumin (CuR) nanoparticles is developed, designated as CuRG, which is also combined with traditional naturopathic scraping (Gua Sha, SCR) as a multifunctional therapy for AGA. With the assistance of lipophilic OG and SCR, CuR can efficaciously penetrate the epidermal and dermal regions where most hair follicles (HFs) reside, thereby releasing curcumin (CR) and copper ions (Cu
Interferon-stimulated neutrophils as a predictor of immunotherapy response
Authors: Madeleine Benguigui, Tim J. Cooper, Prajakta Kalkar, Sagie Schif-Zuck, Ruth Halaban, Antonella Bacchiocchi, Iris Kamer, Abhilash Deo, Bar Manobla, Rotem Menachem, Jozafina Haj-Shomaly, Avital Vorontsova, Ziv Raviv, Chen Buxbaum, Petros Christopoulos, Jair Bar, Michal Lotem, Mario Sznol, Amiram Ariel, Shai S. Shen-Orr, Yuval Shaked
Journal: Cancer Cell (2024)

Despite the remarkable success of anti-cancer immunotherapy, its effectiveness remains confined to a subset of patients—emphasizing the importance of predictive biomarkers in clinical decision-making and further mechanistic understanding of treatment response. Current biomarkers, however, lack the power required to accurately stratify patients. Here, we identify interferon-stimulated, Ly6Ehi neutrophils as a blood-borne biomarker of anti-PD1 response in mice at baseline. Ly6Ehi neutrophils are induced by tumor-intrinsic activation of the STING (stimulator of interferon genes) signaling pathway and possess the ability to directly sensitize otherwise non-responsive tumors to anti-PD1 therapy, in part through IL12b-dependent activation of cytotoxic T cells. By translating our pre-clinical findings to a cohort of patients with non-small cell lung cancer and melanoma (n = 109), and to public data (n = 1440), we demonstrate the ability of Ly6Ehi neutrophils to predict immunotherapy response in humans with high accuracy (average AUC ≈ 0.9). Overall, our study identifies a functionally active biomarker for use in both mice and humans.