tbuckley/cabot-search huggingface dataset:
Induced pluripotent stem-cell-derived corneal epithelium for transplant surgery: a single-arm, open-label, first-in-human interventional study in Japan
Authors: Takeshi Soma, Yoshinori Oie, Hiroshi Takayanagi, Shoko Matsubara, Tomomi Yamada, Masaki Nomura, Yu Yoshinaga, Kazuichi Maruyama, Atsushi Watanabe, Kayo Takashima, Zaixing Mao, Andrew J Quantock, Ryuhei Hayashi, Kohji Nishida
Journal: The Lancet (2024)

SummaryBackgroundThe loss of corneal epithelial stem cells from the limbus at the edge of the cornea has severe consequences for vision, with the pathological manifestations of a limbal stem-cell deficiency (LSCD) difficult to treat. Here, to the best of our knowledge, we report the world's first use of corneal epithelial cell sheets derived from human induced pluripotent stem cells (iPSCs) to treat LSCD.MethodsThis non-randomised, single-arm, clinical study involved four eyes of four patients with LSCD at the Department of Ophthalmology, Osaka University Hospital. They comprised a woman aged 44 years with idiopathic LSCD (patient 1), a man aged 66 years with ocular mucous membrane pemphigoid (patient 2), a man aged 72 years with idiopathic LSCD (patient 3), and a woman aged 39 years with toxic epidermal necrosis (patient 4). Allogeneic human iPSC-derived corneal epithelial cell sheets (iCEPSs) were transplanted onto affected eyes. This was done sequentially in two sets of HLA-mismatched surgeries, with patients 1 and 2 receiving low-dose cyclosporin and patients 3 and 4 not. The primary outcome measure was safety, ascertained by adverse events. These were monitored continuously throughout the 52-week follow-up period, and during an additional 1-year safety monitoring period. Secondary outcomes, reflective of efficacy, were also recorded. This study is registered with UMIN, UMIN000036539 and is complete.FindingsPatients were enrolled between June 17, 2019 and Nov 16, 2020. We had 26 adverse events during the 52-week follow-up period (consisting of 18 mild and one moderate event in treated eyes, and seven mild non-ocular events), with nine recorded in the additional 1-year safety monitoring period. No serious adverse events, such as tumourigenesis or clinical rejection, occurred during the whole 2-year observational period. At 52 weeks, secondary measures of efficacy showed that the disease stage had improved, corrected distance visual acuity was enhanced, and corneal opacification had diminished in all treated eyes. Corneal epithelial defects, subjective symptoms, quality-of-life questionnaire scores and corneal neovascularisation mostly improved or were unchanged. Overall, the beneficial efficacy outcomes achieved for patients 1 and 2 were better than those achieved for patients 3 and 4.InterpretationiCEPS transplantation for LSCD was found to be safe throughout the study period. A larger clinical trial is planned to further investigate the efficacy of the procedure.FundingThe Japan Agency for Medical Research and Development, the Ministry of Education, Culture, Sports, Science, and Technology—Japan, and the UK Biotechnology and Biological Sciences Research Council.
Disparities in wellbeing in the USA by race and ethnicity, age, sex, and location, 2008–21: an analysis using the Human Development Index
Authors: Laura Dwyer-Lindgren, Parkes Kendrick, Mathew M Baumann, Zhuochen Li, Chris Schmidt, Dillon O Sylte, Farah Daoud, Wichada La Motte-Kerr, Robert W Aldridge, Catherine Bisignano, Simon I Hay, Ali H Mokdad, Christopher J L Murray
Journal: The Lancet (2024)
Stem cell exosomes: new hope and future potential for relieving liver fibrosis
Authors: Lihua Li, Yongjie Liu, Kunpeng Wang, Jinggang Mo, Zhiyong Weng, Hao Jiang, Chong Jin
Journal: Clinical and Molecular Hepatology (2024)

Liver fibrosis is a chronic liver injury resulting from factors like viral hepatitis, autoimmune hepatitis, non-alcoholic steatohepatitis, fatty liver disease, and cholestatic liver disease. Liver transplantation is currently the gold standard for treating severe liver diseases. However, it is limited by a shortage of donor organs and the necessity for lifelong immunosuppressive therapy. Mesenchymal stem cells (MSCs) can differentiate into various liver cells and enhance liver function when transplanted into patients due to their differentiation and proliferation capabilities. Therefore, it can be used as an alternative therapy for treating liver diseases, especially for liver cirrhosis, liver failure, and liver transplant complications. However, due to the potential tumorigenic effects of MSCs, researchers are exploring a new approach to treating liver fibrosis using extracellular vesicles (exosomes) secreted by stem cells. Many studies show that exosomes released by stem cells can promote liver injury repair through various pathways, contributing to the treatment of liver fibrosis. In this review, we focus on the molecular mechanisms by which stem cell exosomes affect liver fibrosis through different pathways and their potential therapeutic targets. Additionally, we discuss the advantages of exosome therapy over stem cell therapy and the possible future directions of exosome research, including the prospects for clinical applications and the challenges to be overcome.
Research and product development for Crimean–Congo haemorrhagic fever: priorities for 2024–30
Authors: Amanda E Semper, Janie Olver, Jenny Warner, Ana Cehovin, Petra C Fay, Peter J Hart, Josephine P Golding, Virginia Benassi, Marie-Pierre Preziosi, Khdair Hazbar Razzaq Al-Asadi, Lucille H Blumberg, José de la Fuente, Nazif Elaldi, Tom Fletcher, Pierre B H Formenty, Mohammad Mehdi Gouya, Stephan Günther, Roger Hewson, Bushra Jamil, Gary Kobinger, Gülay Korukluoglu, Laetitia Lempereur, Gustavo Palacios, Anna Papa, Natalia Pshenichnaya, Connie Schmaljohn, Samba O Sow, Hein Sprong, Zati Vatansever, Timothy J G Brooks
Journal: The Lancet Infectious Diseases (2024)
Neoadjuvant and adjuvant toripalimab for locoregionally advanced nasopharyngeal carcinoma: a randomised, single-centre, double-blind, placebo-controlled, phase 2 trial
Authors: Sai-Lan Liu, Xiao-Yun Li, Jin-Hao Yang, Dong-Xiang Wen, Shan-Shan Guo, Li-Ting Liu, Yi-Fu Li, Mei-Juan Luo, Si-Yi Xie, Yu-Jing Liang, Xue-Song Sun, Zhen-Chong Yang, Xiao-Fei Lv, Dong-Hua Luo, Ji-Bin Li, Qing Liu, Pan Wang, Ling Guo, Hao-Yuan Mo, Rui Sun, Qi Yang, Kai-Qi Lan, Guo-Dong Jia, Ru Li, Chong Zhao, Rui-Hua Xu, Qiu-Yan Chen, Lin-Quan Tang, Hai-Qiang Mai
Journal: The Lancet Oncology (2024)
HIV-related outcomes among migrants living in Europe compared with the general population: a systematic review and meta-analysis
Authors: Francesco Vladimiro Segala, Francesco Di Gennaro, Luisa Frallonardo, Elda De Vita, Valentina Petralia, Vitalba Sapienza, Stefano Di Gregorio, Mariangela Cormio, Roberta Novara, Giuseppina Rizzo, Mario Barbagallo, Nicola Veronese, Annalisa Saracino
Journal: The Lancet HIV (2024)
A series of patients infected with the emerging tick-borne Yezo virus in China: an active surveillance and genomic analysis
Authors: Ming-Zhu Zhang, Cai Bian, Run-Ze Ye, Xiao-Ming Cui, Nan-Nan Yao, Ji-Hu Yang, Yan-Li Chu, Xiao-Ling Su, Ya-Fei Wu, Jin-Ling Ye, Shun-Shuai Liu, Xiao-Yu Shi, Wenqiang Shi, Na Jia, Yu-Guo Chen, Lin Zhao, Yuan-Chun Zheng, Xiao-Min Zheng, Jia-Fu Jiang, Wu-Chun Cao
Journal: The Lancet Infectious Diseases (2024)
Artificial daylight photodynamic therapy using methyl aminolevulinate in a real-world setting in Germany - Results from the non-interventional study ArtLight
Authors: Wolfgang G Philipp-Dormston, Matthias Brückner, Matthias Hoffmann, Melvin Baé, Jörg Fränken, Bernd Großmann, Uwe Paasch, Sven Quist, Berenice M Lang, Rajeev Chavda, Rolf-Markus Szeimies
Journal: British Journal of Dermatology (2024)

Artificial daylight photodynamic therapy (ADL-PDT) is an alternative, all-year applicable, nearly painless treatment approach for actinic keratoses (AK) with comparable effectiveness to daylight or conventional PDT. At the time this study was initiated, methyl aminolevulinate (MAL) was the only photosensitizer approved for ADL-PDT in Germany.
A sequence bottleneck for animal intelligence and language?
Authors: Johan Lind, Anna Jon-And
Journal: Trends in Cognitive Sciences (2024)

We discuss recent findings suggesting that non-human animals lack memory for stimulus sequences, and therefore do not represent the order of stimuli faithfully. These observations have far-reaching consequences for animal cognition, neuroscience, and studies of the evolution of language and culture. This is because, if non-human animals do not remember or process information about order faithfully, then it is unlikely that non-human animals perform mental simulations, construct mental world models, have episodic memory, or transmit culture faithfully. If this suggested sequence bottleneck proves to be a prevalent characteristic of animal memory systems, as suggested by recent work, it would require a re-examination of some influential concepts and ideas.
Artificial General Intelligence for Medical Imaging Analysis
Authors: Xiang Li, Lin Zhao, Lu Zhang, Zihao Wu, Zhengliang Liu, Hanqi Jiang, Chao Cao, Shaochen Xu, Yiwei Li, Haixing Dai, Yixuan Yuan, Jun Liu, Gang Li, Dajiang Zhu, Pingkun Yan, Quanzheng Li, Wei Liu, Tianming Liu, Dinggang Shen
Journal: IEEE Reviews in Biomedical Engineering (2024)

Large-scale Artificial General Intelligence (AGI) models, including Large Language Models (LLMs) such as ChatGPT/GPT-4, have achieved unprecedented success in a variety of general domain tasks. Yet, when applied directly to specialized domains like medical imaging, which require in-depth expertise, these models face notable challenges arising from the medical field's inherent complexities and unique characteristics. In this review, we delve into the potential applications of AGI models in medical imaging and healthcare, with a primary focus on LLMs, Large Vision Models, and Large Multimodal Models. We provide a thorough overview of the key features and enabling techniques of LLMs and AGI, and further examine the roadmaps guiding the evolution and implementation of AGI models in the medical sector, summarizing their present applications, potentialities, and associated challenges. In addition, we highlight potential future research directions, offering a holistic view on upcoming ventures. This comprehensive review aims to offer insights into the future implications of AGI in medical imaging, healthcare, and beyond.
Global landscape of COVID-19 vaccination programmes for older adults: a descriptive study
Authors: Wen Zheng, Jiayi Dong, Zhiyuan Chen, Xiaowei Deng, Qianhui Wu, Lance E Rodewald, Hongjie Yu
Journal: The Lancet Healthy Longevity (2024)

SummaryBackgroundTo minimise severe cases and deaths from COVID-19 among high-risk populations such as older adults (aged 60 years and older), it is crucial to monitor and update vaccination strategies. In this study, we aim to provide a global profile of the current COVID-19 vaccination programmes for older adults, including vaccination policies, coverage rates, and vaccine demand.MethodsWe used publicly available data on the COVID-19 vaccines used, vaccination schedules, indicated age groups, and age-specific country-level vaccine coverage, updated through to July 20, 2024. Data on vaccination policy were extracted from publicly available sources in the following priority: (1) official sources (ie, government websites, health department websites, and official reports); (2) resources integrated by institutions or organisations (ie, European Center for Disease Prevention and Control, Africa Center for Disease Prevention and Control, and COVAX); and (3) cross-validated news and media reports derived from government or health department sources. We estimated coverage gaps to achievement of two specific objectives: (1) immunising 100% of older adults with primary series and a booster dose, as per WHO's goal; and (2) surpassing WHO's goal by administering one extra booster dose to 80% of older adults or achieving 80% coverage of a 2023–24 series vaccine.Findings192 countries reported their use of COVID-19 vaccines for older people, of which 71 vaccine products have been used for older adults and 79 countries have deployed 22 vaccines containing components against variants of concern; 122 countries offered a second booster dose or a special booster dose, while others used only primary series or one booster dose. 96 countries prioritised older people for vaccination. Among countries with available data, the median proportion of individuals completing a primary series was 81% (IQR 58·3–92·0), for a first booster was 53% (14·1–81·7), for a second booster was 44·3% (13·5–69·7), and for a 2023–24 series vaccination was 23·6% (6·6–52·4), with large differences by region. Coverage of the second booster and the 2023–24 series was lower in individuals aged 60–70 years than in older age groups. To achieve the WHO target of 100% coverage for older populations with primary series and a booster dose, 1·01 doses per person are required, and to attain an 80% coverage for a second booster or 2023–24 series, surpassing WHO's goal, 1·43 doses per person are required.InterpretationProgress of COVID-19 vaccination programmes for older adults is uneven across countries, emphasising an ongoing challenge to achieve vaccine equity for this high-risk age group. Therefore, it is essential to establish robust and timely vaccination surveillance systems, especially to facilitate data-driven policies that promote COVID-19 vaccination campaigns worldwide.FundingKey Program of the National Natural Science Foundation of China.
Durvalumab Versus Chemotherapy as First-line Treatment for Metastatic NSCLC With Tumor PD-L1 Expression ≥25%: Results from the Randomized Phase 3 PEARL Study
Authors: Shun Lu, Lin Wu, Qiming Wang, Ziping Wang, Dongqing Lv, Rui Ma, Bo Zhu, Ngoc van Tran, Liyan Jiang, Kejun Nan, Konstantin Laktionov, Stephen Clarke, Minghao Song, Helen Mann, Yinglei Liu, Xiaojin Shi, Yi-Long Wu
Journal: Journal of Thoracic Oncology (2024)
Reversing metabolic reprogramming by CPT1 inhibition with etomoxir promotes cardiomyocyte proliferation and heart regeneration via DUSP1 ADP-ribosylation-mediated p38 MAPK phosphorylation
Authors: Luxun Tang, Yu Shi, Qiao Liao, Feng Wang, Hao Wu, Hongmei Ren, Xuemei Wang, Wenbin Fu, Jialing Shou, Wei Eric Wang, Pedro A Jose, Yongjian Yang, Chunyu Zeng
Journal: Acta Pharmaceutica Sinica B (2024)

The neonatal mammalian heart has a remarkable regenerative capacity, while the adult heart has difficulty to regenerate. A metabolic reprogramming from glycolysis to fatty acid oxidation occurs along with the loss of cardiomyocyte proliferative capacity shortly after birth. In this study, we sought to determine if and how metabolic reprogramming regulates cardiomyocyte proliferation. Reversing metabolic reprogramming by carnitine palmitoyltransferase 1 (CPT1) inhibition, using cardiac-specific Cpt1a and Cpt1b knockout mice promoted cardiomyocyte proliferation and improved cardiac function post-myocardial infarction. The inhibition of CPT1 is of pharmacological significance because those protective effects were replicated by etomoxir, a CPT1 inhibitor. CPT1 inhibition, by decreasing poly(ADP-ribose) polymerase 1 expression, reduced ADP-ribosylation of dual-specificity phosphatase 1 in cardiomyocytes, leading to decreased p38 MAPK phosphorylation, and stimulation of cardiomyocyte proliferation. Our present study indicates that reversing metabolic reprogramming is an effective strategy to stimulate adult cardiomyocyte proliferation. CPT1 is a potential therapeutic target for promoting heart regeneration and myocardial infarction treatment.
Induction of Cyp2e1 contributes to asparaginase-induced hepatocyte sensitization to lipotoxicity
Authors: Yin Zhu, Yuyin Wang, Keito Hoshitsuki, Da Yang, Lauren Kokai, Xiaochao Ma, Wen Xie, Christian A Fernandez
Journal: Acta Pharmaceutica Sinica B (2024)

One of the leading therapies for acute lymphoblastic leukemia (ALL) is the chemotherapeutic agent PEGylated E. coli-derived-l-asparaginase (PEG-ASNase). Due to the high risk of dose-limiting liver injury, characterized by clinically elevated levels of hepatic transaminases, PEG-ASNase therapy is generally avoided in adult patients. Our preclinical investigations have indicated that PEG-ASNase-induced liver injury is associated with the release of free fatty acids (FFAs) from white adipose tissue (WAT), suggesting potential lipotoxic effects. However, it remains uncertain whether PEG-ASNase directly induces hepatotoxicity or sensitizes hepatocytes to FFA-induced toxicity. Our results show that PEG-ASNase treatment results in hepatocyte apoptosis and lipid peroxidation. Ex vivo and in vitro studies in mouse and human WAT suggest that PEG-ASNase induces the expression of adipose triglyceride lipase (ATGL), activates the lipase, and stimulates adipose tissue lipolysis, suggesting that the FFAs from WAT may contribute to the observed liver injury. Moreover, treatment with PEG-ASNase sensitizes hepatocytes to FFA-induced lipotoxicity. Mechanistically, our RNA-sequencing (RNA-seq) analyses reveal that PEG-ASNase-induced sensitization to lipotoxicity is accompanied by the induction of Cyp2e1. We demonstrated that this sensitization effect is attenuated by both pharmacological and genetic inhibition of Cyp2e1. Our findings suggest that PEG-ASNase therapy induces WAT lipolysis and sensitizes hepatocytes to hepatic lipotoxicity in a Cyp2e1-dependent manner.
Identifying future research priorities in the field of interpersonal violence (IV) towards athletes in sport: a Delphi study
Authors: Sylvie Parent, Stephanie Radziszewski, Osazemen Aghedo, Isabelle Daignault, Emma Kavanagh, Melanie Lang, Margo Mountjoy, Aurélie Pankowiak, Julia Topart, Mary Woessner, Tine Vertommen
Journal: British Journal of Sports Medicine (2024)

Objective Our aim was to define the priorities for future research in safeguarding athletes from interpersonal violence (IV) in sport through a Delphi consensus study of researchers in the field. Methods An internet-based three-round Delphi method was used as a multistage facilitation technique to arrive at a group consensus (set at ≥75% agreement). A targeted literature search was conducted to develop a list of potential research priorities that were presented as short statements in the first round. Results A total of 52 participants (researchers in IV in sport) took part in the first round, 52 completed the second round and 44 completed the third round. Respectively, 47 items, 83 items and 60 items were included in each round. The participants achieved consensus on 11 statements in the first round, seven in the second round and 31 in the third round, for a total of 49 consensus research priorities. The first four priorities that reached consensus (78.8–80.8% agreement) directly following the first Delphi round were scored with high importance (between 6.2 and 6.3 on a scale of 7). Those four priorities included: (1) documenting the experiences of children athletes and minors, (2) studying the disclosure or reporting of violence, (3) developing, evaluating and advising on interventions targeting education and training and (4) documenting the experiences of violence of para athletes. Conclusion This study defines research priorities for IV in sport that may elucidate further gaps in current policies and practices.
Molecular basis for the disease-modifying effects of belimumab in systemic lupus erythematosus and molecular predictors of early response: blood transcriptome analysis implicates the innate immunity and DNA damage response pathways
Authors: Georgia-Savina Moysidou, Panagiotis Garantziotis, George Sentis, Dimitra Nikoleri, Nikolaos Malissovas, Myrto Nikoloudaki, Eirini-Maria Stergioti, Styliani Polia, Nikolaos Paschalidis, Anastasia Filia, Maria Grigoriou, Dionysis Nikolopoulos, Noemin Kapsala, Spyridon Katechis, Antonis Fanouriakis, George Bertsias, Dimitrios T. Boumpas
Journal: Annals of the Rheumatic Diseases (2024)

Belimumab is a putative disease-modifying agent in systemic lupus erythematosus (SLE), yet the molecular underpinnings of its effects and the ability to predict early clinical response remain unexplored. To address these, we undertook a longitudinal, in-depth blood transcriptome study. RNA-sequencing was performed in the blood of active SLE patients at baseline and following 6 months of belimumab treatment (n=45 paired samples). Clinical response was determined according to the SLE Responder Index (SRI)-4 and Lupus Low Disease Activity State (LLDAS). Weighted correlation network analysis (WGCNA) was used to uncover gene module trait associations. Reversibility of SLE susceptibility and severity gene signatures was assessed. Machine learning was used to build models predictive of response. Belimumab induced widespread transcriptome changes with downregulation of pathways related to B cells, type I/II interferon, IL-6/STAT3 and neutrophil activation. These effects were more pronounced among patients with LLDAS+ compared with to SRI-4+/LLDAS- response, with amelioration of the SLE 'susceptibility' signature observed in the former group. Unsupervised analysis unveiled gene modules enriched in neutrophil degranulation, type I interferon signalling and cytokine production to correlate positively with response at 6 months. Using neural networks, a set of 50 genes (including CCL4L2, CARD10, MMP15 and KLRC2) predicted response to belimumab with a cross-validated 84% specificity (test set). Lack of response was linked to perturbations of the cell cycle checkpoints, PI3K/Akt/mammalian target of rapamycin and TGF-beta signalling pathways. Belimumab treatment ameliorates multiple innate and adaptive immunity dysregulations of SLE and may reverse the disease signature, consistent with the drug effects on reducing activity and preventing flares. Fingerprints of innate immunity correlate with robust improvement whereas DNA damage response with less responsive disease to BAFF inhibition.
Prospective observational study and mechanistic evidence showing lipolysis of circulating triglycerides worsens hypertriglyceridemic acute pancreatitis
Authors: Prasad Rajalingamgari, Biswajit Khatua, Megan J. Summers, Sergiy Kostenko, Yu-Hui H Chang, Mohamed Elmallahy, Arti Anand, Anoop Narayana Pillai, Mahmoud Morsy, Shubham Trivedi, Bryce McFayden, Sarah Jahangir, Christine LH Snozek, Vijay P. Singh
Journal: Journal of Clinical Investigation (2024)

While most hypertriglyceridemia is asymptomatic, hypertriglyceridemia-associated acute pancreatitis (HTG-AP) can be more severe than other AP etiologies. The reasons underlying this are unclear. We thus studied whether lipolytic generation of non-esterified fatty acids (NEFA) from circulating triglycerides (TGs) could worsen clinical outcomes.
Para athlete concussion care following the Amsterdam 2022 International Consensus Statement on Concussion in Sport: an urgent need for inclusivity within concussion research
Authors: Richard Weiler, Kristine Dalton, Anna Guenther, Katelyn Mitchell, Peter Van de Vliet, Shelina Babul, Cheri Blauwet, David Clarke, Jenny Dea, Wayne Derman, Carolyn Emery, Kristina Fagher, Vincent Gouttebarge, Mohammad Nadir Haider, Tamerah Hunt, Kenneth Lee, Jan Lexell, Ryan N Moran, Francine Pilon, Francois Prince, Phoebe Runciman, Racheal Smetana, Evert Verhagen, Nick Webborn, Osman Hassan Ahmed
Journal: British Journal of Sports Medicine (2024)
Current status and future directions in Food Protein-Induced Enterocolitis Syndrome (FPIES): An NIAID Workshop Report
Authors: Anna Nowak-Wegrzyn, Scott H. Sicherer, Cem Akin, Sara Anvari, Lisa M. Bartnikas, M. Cecilia Berin, Theresa A. Bingemann, Scott Boyd, Terri Brown-Whitehorn, Supinda Bunyavanich, Antonella Cianferoni, George du Toit, John E. Fortunato, Jeffrey D. Goldsmith, Marion Groetch, Stephanie A. Leonard, Meenakshi Rao, Fallon Schultz, Julie M. Schwaninger, Carina Venter, Amity Westcott-Chavez, Robert A. Wood, Alkis Togias
Journal: Journal of Allergy and Clinical Immunology (2024)