tbuckley/cabot-search huggingface dataset:
Dietary modulation of gut microbiota affects susceptibility to drug-induced liver injury
Authors: Han Pan, Delei Song, Zhiyi Wang, Xin Yang, Pei Luo, Wei Li, Yan Li, Mengxue Gong, Chenhong Zhang
Journal: Gut Microbes (2024)

The rising incidence of drug-induced liver injury (DILI) parallels contemporary dietary shifts that have transformed the composition of human gut microbiota. The relationship between these phenomena remains unknown. Here, it is unveiled that a high fiber diet (HFiD) provides substantial protection against DILI, whereas a western style diet (WSD) significantly exacerbates DILI. Gut microbiota transplantation further confirms these differing outcomes are mediated by diet-induced variations in gut microbiota. Mechanistically, Lactobacillus acidophilus, enriched by HFiD, alleviates DILI through its metabolite indole-3-lactic acid (ILA), which activates the AhR/Nrf2 signaling pathway, thus enhancing hepatocellular antioxidant defenses and detoxification capacity. In the clinical intervention of subjects with prediabetes (N = 330), dietary fiber intervention enriches intestinal L. acidophilus, elevates serum ILA levels, and improves liver function. Conversely, WSD induces disturbance in bile acid metabolism and dysbiosis in gut microbiota, which impairs the intestinal barrier and facilitates the translocation of lipopolysaccharides (LPS) to the liver, thus triggering inflammatory responses and exacerbating DILI. These results demonstrate that dietary patterns significantly influence the onset of DILI by modulating gut microbiota. This novel insight expands the understanding of DILI risk factors and highlights the potential of dietary modifications as a preventive strategy against DILI.
When I use a word . . . Academic integrity—defining misdemeanours
Authors: Jeffrey K Aronson
Journal: BMJ (2024)

In contrast to the three major forms of academic research misconduct, which I have called felonies (namely fabrication, falsification, and plagiarism), it is more difficult to identify and define more minor questionable research practices, which I have called misdemeanours. Recognising that academic felonies and misdemeanours can affect not only research but other academic activities, I offer the following general definition of an academic misdemeanour: "Any minor violation or infringement of an academic norm or norms, short of the major violations of fabrication, falsification, and plagiarism." I also offer a list of 22 activities that together can be regarded as an extensional definition of academic misdemeanours.
Fast intraoperative detection of primary CNS lymphoma and differentiation from common CNS tumors using stimulated Raman histology and deep learning
Authors: David Reinecke, Nader Maarouf, Andrew Smith, Daniel Alber, John Markert, Nicolas K Goff, Todd C Hollon, Asadur Chowdury, Cheng Jiang, Xinhai Hou, Anna-Katharina Meissner, Gina Fürtjes, Maximilian I Ruge, Daniel Ruess, Thomas Stehle, Abdulkader Al-Shughri, Lisa I Körner, Georg Widhalm, Thomas Roetzer-Pejrimovsky, John G Golfinos, Matija Snuderl, Volker Neuschmelting, Daniel A Orringer
Journal: Neuro-Oncology (2024)

Abstract Background Accurate intraoperative diagnosis is crucial for differentiating between primary CNS lymphoma (PCNSL) and other CNS entities, guiding surgical decision-making, but represents significant challenges due to overlapping histomorphological features, time constraints, and differing treatment strategies. We combined stimulated Raman histology (SRH) with deep learning to address this challenge. Methods We imaged unprocessed, label-free tissue samples intraoperatively using a portable Raman scattering microscope, generating virtual H&amp;E-like images within less than three minutes. We developed a deep learning pipeline called RapidLymphoma based on a self-supervised learning strategy to (1) detect PCNSL, (2) differentiate from other CNS entities, and (3) test the diagnostic performance in a prospective international multicenter cohort and two additional independent test cohorts. We trained on 54,000 SRH patch images sourced from surgical resections and stereotactic-guided biopsies, including various CNS neoplastic/non-neoplastic lesions. Training and test data were collected from four tertiary international medical centers. The final histopathological diagnosis served as ground-truth. Results In the prospective test cohort of PCNSL and non-PCNSL entities (n=160), RapidLymphoma achieved an overall balanced accuracy of 97.81% ±0.91, non-inferior to frozen section analysis in detecting PCNSL (100% vs. 77.77%). The additional test cohorts (n=420, n=59) reached balanced accuracy rates of 95.44% ±0.74 and 95.57% ±2.47 in differentiating IDH-wildtype diffuse gliomas and various brain metastasis from PCNSL. Visual heatmaps revealed RapidLymphoma’s capabilities to detect class-specific histomorphological key features. Conclusions RapidLymphoma proves reliable and valid for intraoperative PCNSL detection and differentiation from other CNS entities. It provides visual feedback within three minutes, enabling fast clinical decision-making and subsequent treatment strategy planning.
A novel nuclear RNA HSD52 scaffolding NONO/SFPQ complex modulates DNA damage repair to facilitate temozolomide resistance
Authors: Nan Sun, Qun Chen, Hao Chen, Penggang Sun, Yuxiang Liu, Dan Song, Daohan Yu, Pandeng Wang, Yu Song, Jie Qin, Kaifu Tian, Junzhe Zhong, Wenbin Ma, Hanwen Xuan, Da Qian, Ye Yuan, Tongzheng Chen, Xin Wang, Chuanlu Jiang, Jinquan Cai, Xiangqi Meng
Journal: Neuro-Oncology (2024)

Abstract Background Temozolomide (TMZ) is used in the treatment of glioblastoma (GBM). However, the primary obstacle remains the emergence of TMZ chemotherapy resistance. NONO and SFPQ are multifunctional nuclear proteins involved in genome stability and gene regulation. However, the specific role of NONO and SFPQ in TMZ resistance of GBM remains to be explored. Methods RIP-chip and RNA microarray of TMZ-resistant and parental cells were performed for the gain of HSD52. The effects of HSD52 on TMZ resistance were investigated through in vitro assays, intracranial xenograft and GBM organoid models. The underlying mechanisms were explored by DNA methylation chip, RIP, RNA pulldown assays, among others. GBM clinical samples were rolled in to investigate the clinical significance of HSD52. Results We identified a novel non-coding RNA, HSD52, that was highly expressed in TMZ-resistant GBM and facilitated the interaction between NONO and SFPQ. H3 ubiquitination attenuation and reduced DNMT1 recruitment increased HSD52 transcription via DNA hypo-methylation. HSD52 formed an RNA duplex with UFL1 mRNA, thereby promoting NONO/SFPQ complex binding to UFL1 mRNA and enhancing its stability, and then contributed to TMZ resistance through activating ATM signaling pathway. In vivo xenograft and GBM organoid models showed significant repression in tumor growth after HSD52 knockout with TMZ treatment. In GBM clinical samples, HSD52 was responsible for the malignant progression and TMZ resistance. Conclusions Our results revealed that HSD52 could serve as a promising therapeutic target to overcome TMZ resistance, improving the clinical efficacy of TMZ chemotherapy in GBM.
The emerging role of regulatory T cells in the immunopathogenesis of vitiligo and implications for treatment
Authors: Yang Liu, Ziqi Liu, Dan Li, Xuanxuan He, Leihong Xiang, Bin Li, Chengfeng Zhang
Journal: British Journal of Dermatology (2024)

Vitiligo is an autoimmune skin disease that targets pigment-producing melanocytes and results in depigmentation. This disfiguring condition frequently affects visible areas of the body and therefore causes a heavy psychological burden and a decreased quality of life. Although remains intractable, the evergrowing understanding of its immunopathogenesis has dramatically shaped the treatment paradigm for vitiligo. With the impact of autoreactive cytotoxic T cells explained extensively, accumulating evidence suggests the unique role of regulatory T (Treg) cells in the immune microenvironment of vitiligo. We systematically reviewed Treg deficiency, instability, reduced vitality and dysfunction reported in vitiligo patients, combined with novel findings regarding Treg function modulation in autoimmune backgrounds including metabolic alteration, post-translational modifications and interaction with other immune cells. We further summarized classic and advanced Treg-targeted therapeutics in vitiligo practice and research. Herein, we aimed to display the updated knowledge of Treg cells in vitiligo, providing insights into novel Treg-based therapeutic strategies.
Advancements and Applications of Artificial Intelligence in Cardiovascular Imaging: a Comprehensive Review
Authors: Federico Fortuni, Giuseppe Ciliberti, Benedetta De Chiara, Edoardo Conte, Luca Franchin, Francesca Musella, Enrica Vitale, Francesco Piroli, Stefano Cangemi, Stefano Cornara, Michele Magnesa, Antonella Spinelli, Giovanna Geraci, Federico Nardi, Domenico Gabrielli, Furio Colivicchi, Massimo Grimaldi, Fabrizio Oliva
Journal:  (2024)

Abstract Artificial intelligence (AI) is transforming cardiovascular imaging by offering advancements across multiple modalities, including echocardiography, cardiac computed tomography (CCT), cardiovascular magnetic resonance (CMR), interventional cardiology, nuclear medicine, and electrophysiology. This review explores the clinical applications of AI within each of these areas, highlighting its ability to improve patient selection, reduce image acquisition time, enhance image optimization, facilitate the integration of data from different imaging modality and clinical sources, improve diagnosis and risk stratification. Moreover, we illustrate both the advantages and the limitations of AI across these modalities, acknowledging that while AI can significantly aid in diagnosis, risk stratification, and workflow efficiency, it cannot replace the expertise of cardiologists. Instead, AI serves as a powerful tool to streamline routine tasks, allowing clinicians to focus on complex cases where human judgement remains essential. By accelerating image interpretation and improving diagnostic accuracy, AI holds great potential to improve patient care and clinical decision-making in cardiovascular imaging.
<i>TP53</i> missense allele predisposing to high risk of breast cancer but not pediatric cancers
Authors: Suhair Lolas-Hamameh, Sari Lieberman, Alaa Sarahneh, Tom Walsh, Ming K Lee, Suleyman Gulsuner, Grace Rabie, Rachel Beeri, Amal Aburayyan, Jessica B Mandell, Hila Fridman, Galit Lazer-Derbeko, Tehila Klopstock, Orit Freireich, Amnon Lahad, Mary-Claire King, Ephrat Levy-Lahad, Moien N Kanaan
Journal: JNCI Journal of the National Cancer Institute (2024)

Pathogenic TP53 germline variants cause young-onset breast cancer and other cancers of the Li-Fraumeni syndrome (LFS) spectrum, but the clinical consequences of partial-loss-of function TP53 variants are incompletely understood. In the consecutive cohort of Palestinian breast cancer patients of the Middle East Breast Cancer Study (MEBCS), breast cancer risk among TP53 p. R181C heterozygotes was 50% by age 50 y and 81% by age 80 y. In contrast, prevalence of pediatric cancers in the MEBCS was similar among first degree relatives of TP53 p. R181C carriers (3/519 = 0.0058) and first degree relatives of MEBCS patients with no pathogenic germline variant in any known breast cancer gene (7/1082 = 0.0065; OR = 0.90, 95%CI [0.23,3.49], Fisher P = .90 (2-tailed)). This result suggests that in families harboring this TP53 allele, genetic testing in children is unwarranted, and screening children for LFS tumors is unnecessary. More generally, some TP53 missense alleles can predispose to very high risk of breast cancer without pleiotropic effects.
Acute Severe Ulcerative Colitis: An International Delphi Consensus on Clinical Trial Design and Endpoints
Authors: Sailish Honap, Vipul Jairath, Bruce E Sands, Parambir S Dulai, Peter D R Higgins, Peter De Cruz, Ana Gutiérrez, Paulo G Kotze, Byong Duk Ye, Taku Kobayashi, Richard B Gearry, Pablo A Olivera, Aurélien Amiot, Mahmoud H Mosli, Sameer Al Awadhi, Jonas Halfvarson, Kamal V Patel, Shaji Sebastian, Silvio Danese, Laurent Peyrin-Biroulet
Journal: Clinical Gastroenterology and Hepatology (2024)

Interventional clinical trials in ASUC are characterised by substantial heterogeneity due to a lack of consensus in several key areas of trial design - this impedes clinical research efforts to identify novel therapies. The objective of this initiative was to achieve the first consensus and provide clear position statements on ASUC trial design. A modified Delphi consensus approach was employed with a panel of twenty clinicians with international representation and expertise in ASUC trial design and delivery. Agreement was defined as at least 75% of participants voting as 'agree' with each statement. In total, thirty statements achieved consensus and were approved. Statements centred on proposing suitable eligibility criteria (disease extent, disease severity, prior therapy exposure), optimising trial design (randomisation, stratification, corticosteroid handling, timing of assessments), and recommending primary and secondary endpoints alongside defining key efficacy outcomes (clinical and endoscopic reponse and remission, treatment failure, quality of life). The expansion of drugs to treat moderate-severe UC over the past decade, particularly the rapidly acting Janus kinase inhibitors, is promising and has reignited the interest in identifying suitable therapeutic candidates for ASUC. Clinical trials in this high-risk population are challenging to conduct and this consensus provides a framework for future trials to advance drug development.
A Call to Action: Unraveling the Nuance of Adapted Eating Behaviors in Individuals with GI Conditions.
Authors: Kate Scarlata, Hana F Zickgraf, Rose-Marie Satherley, Jordan M Shapiro, Dawn W Adams, Janelle Smith, Stacey Collins, Tiffany Taft
Journal: Clinical Gastroenterology and Hepatology (2024)
Multi-Niche Human Bone Marrow On-A-Chip for Studying the Interactions of Adoptive CAR-T Cell Therapies with Multiple Myeloma
Authors: Delta Ghoshal, Ingrid Petersen, Rachel Ringquist, Liana Kramer, Eshant Bhatia, Thomas Hu, Ariane Richard, Reda Park, Jenna Corbin, Savi Agarwal, Abel Thomas, Sebastian Ramirez, Jacob Tharayil, Emma Downey, Frank Ketchum, Abigail Ochal, Neha Sonthi, Sagar Lonial, James N Kochenderfer, Reginald Tran, Mandy Zhu, Wilbur A Lam, Ahmet F Coskun, Krishnendu Roy
Journal: Biomaterials (2024)

Multiple myeloma (MM), a cancer of bone marrow plasma cells, is the second-most common hematological malignancy. However, despite immunotherapies like chimeric antigen receptor (CAR)-T cells, relapse is nearly universal. The bone marrow (BM) microenvironment influences how MM cells survive, proliferate, and resist treatment. Yet, it is unclear which BM niches give rise to MM pathophysiology. Here, we present a 3D microvascularized culture system, which models the endosteal and perivascular bone marrow niches, allowing us to study MM-stroma interactions in the BM niche and model responses to therapeutic CAR-T cells. We demonstrated the prolonged survival of cell line-based and patient-derived multiple myeloma cells within our in vitro system and successfully perfused in donor-matched CAR-T cells. We then measured T cell survival, differentiation, and cytotoxicity against MM cells using a variety of analysis techniques. Our MM-on-a-chip system could elucidate the role of the BM microenvironment in MM survival and therapeutic evasion and inform the rational design of next-generation therapeutics.
Macrophage-Hitchhiked, Effervescence-Induced Nanoemulsions for Enhanced Oral Chemotherapy and Immunotherapy: Impact on Absorption Route
Authors: Nhien Nguyen, Tuyet-Mai Hoang, Tun-Yu Huang, Lam-Duc-Huy Nguyen, Hsiao-Huan Chang, Yen Chang, Mai Thanh Thi Nguyen, Kun-Ju Lin, Chun-Chieh Chen, Hsing-Wen Sung
Journal: Biomaterials (2024)
AutoFOX: An automated cross-modal 3D fusion framework of coronary X-ray angiography and OCT
Authors: Chunming Li, Yuchuan Qiao, Wei Yu, Yingguang Li, Yankai Chen, Zehao Fan, Runguo Wei, Botao Yang, Zhiqing Wang, Xuesong Lu, Lianglong Chen, Carlos Collet, Miao Chu, Shengxian Tu
Journal: Medical Image Analysis (2024)
History of Corneal Cross-Linking
Authors: Farhad Hafezi, Sabine Kling, Nikki L Hafezi, M Enes Aydemir, Nan-Ji Lu, Mark Hillen, Boris Knyazer, Shady Awwad, Cosimo Mazzotta, Léonard Kollros, Emilio A Torres-Netto
Journal: Progress in Retinal and Eye Research (2024)
Real-world multicentre study of cefiderocol treatment of immunocompromised patients with infections caused by multidrug-resistant Gram-negative bacteria: CEFI-ID
Authors: Sarah Soueges, Emmanuel Faure, Perrine Parize, Fanny Lanternier-Dessap, Hervé Lecuyer, Anne Huynh, Guillaume Martin-Blondel, Benjamin Gaborit, Mathieu Blot, Arnaud Magallon, Elodie Blanchard, Xavier Brousse, Marin Lahouati, Anne-Sophie Brunel, Eloise Le Banner, François Camelena, Romaric Larcher, Alix Pantel, Giovanna Melica, Keyvan Razazi, François Danion, Frederic Schramm, Oana Dumitrescu, Baptiste Hoellinger, Florence Ader
Journal: Journal of Infection (2024)
Gabapentin improves the flushing of rosacea, but not other rosacea symptoms or quality of life: results from a multi-center, randomized, double-blind, placebo-controlled pilot study
Authors: Guangrong Ma, Yiya Zhang, Qiong Gao, Xin Yuan, Zhonglian Zhou, Dan Jian, Zhixiang Zhao, Ben Wang, Ji Li
Journal: Journal of the American Academy of Dermatology (2024)
Selenium Promotes Neural Development Through the Regulation of GPX4 and SEPP1 in an iPSC-derived Neuronal Model
Authors: Zhenzhu Dai, Yanzi Yu, Ruhai Chen, Hongyao Zhu, Hin Fong, Junxin Kuang, Yunbo Jiang, Yalan Chen, Yimei Niu, Tianfeng Chen, Lingling Shi
Journal: Biomaterials (2024)
Copper doped bioactive glass promotes matrix vesicles-mediated biomineralization via osteoblast mitophagy and mitochondrial dynamics during bone regeneration
Authors: Ziji Ling, Xiao Ge, Chengyu Jin, Zesheng Song, Hang Zhang, Yu Fu, Kai Zheng, Rongyao Xu, Hongbing Jiang
Journal: Bioactive Materials (2024)
Retraction Notice to: Inhibition of Hepatitis C Virus Replication by Intracellular Delivery of Multiple siRNAs by Nanosomes
Authors: Partha K. Chandra, Anup K. Kundu, Sidhartha Hazari, Sruti Chandra, Lili Bao, Tara Ooms, Gilbert F. Morris, Tong Wu, Tarun K. Mandal, Srikanta Dash
Journal: Molecular Therapy (2024)
Advancing Diagnosis in a Cardiac Arrest Case and Suspected MINOCA: The Complementary Roles of Imaging, Biopsy, and Genetic Testing
Authors: Giuseppe Ciliberti, Paolo Compagnucci, Michela Casella, Francesco Schiavone, Monica De Gaspari, Stefania Rizzo, Cristina Basso, Andrea Giovagnoni, Federico Guerra, Giada Tortora, Antonio Dello Russo
Journal:  (2024)
Cardiac Reprogramming and Gata4 Overexpression Reduce Fibrosis and Improve Diastolic Dysfunction in Heart Failure With Preserved Ejection Fraction
Authors: Yu Yamada, Taketaro Sadahiro, Koji Nakano, Seiichiro Honda, Yuto Abe, Tatsuya Akiyama, Ryo Fujita, Masashi Nakamura, Takashi Maeda, Yuta Kuze, Masaya Onishi, Masahide Seki, Yutaka Suzuki, Chikara Takeuchi, Yuka W. Iwasaki, Kensaku Murano, Mamiko Sakata-Yanagimoto, Shigeru Chiba, Hideyuki Kato, Hiroaki Sakamoto, Yuji Hiramatsu, Masaki Ieda
Journal: Circulation (2024)

BACKGROUND: Heart failure with preserved ejection fraction (HFpEF) is a major health concern. Pathological stimuli and interactions between cardiac fibroblasts (CFs) and other cell types may lead to cardiac fibrosis and diastolic dysfunction, which are hallmarks of HFpEF. Interstitial and perivascular cardiac fibrosis correlates with poor prognosis in HFpEF; however, mechanisms of fibrosis remain poorly elucidated, and targeted therapies are lacking. Cardiac reprogramming is a promising therapeutic approach for myocardial infarction that facilitates cardiac regeneration and antifibrosis action through Mef2c/Gata4/Tbx5/Hand2 (MGTH) overexpression in resident CFs. However, the efficacy of this approach on HFpEF is yet to be established. METHODS: Herein, we examined the effects of cardiac reprogramming in HFpEF using Tcf21 iCre /Tomato/MGTH2A transgenic mice, which expressed both MGTH and reporter expression in CFs for cardiac reprogramming and lineage tracing upon tamoxifen administration. To establish HFpEF model mice, we used a combination of a high-fat diet and nitric oxide synthase inhibition. Bulk RNA-sequencing, single-cell RNA-sequencing, and spatial transcriptomics were conducted to determine fibrotic mechanisms and the efficacy of cardiac reprogramming in HFpEF. We generated new tamoxifen-inducible transgenic mice overexpressing each reprogramming factor in CFs to investigate the effect of single factors. Last, we analyzed the effect of reprogramming factors in human CFs. RESULTS: Cardiac reprogramming with MGTH overexpression improved diastolic dysfunction, cardiac hypertrophy, fibrosis, inflammation, and capillary loss in HFpEF. Cardiac reprogramming converted approximately 1% of resident CFs into induced cardiomyocytes. Bulk RNA-seq indicated that MGTH overexpression upregulated genes related to heart contraction and suppressed the fetal gene program ( Nppa and Nppb ) and proinflammatory and fibrotic signatures. Single-cell RNA-sequencing and spatial transcriptomics revealed that multiple CF clusters upregulated fibrotic genes to induce diffuse interstitial fibrosis, whereas distinct CF clusters generated focal perivascular fibrosis in HFpEF. MGTH overexpression reversed these profibrotic changes. Among 4 reprogramming factors, only Gata4 overexpression in CFs reduced fibrosis and improved diastolic dysfunction in HFpEF by suppressing CF activation without generating new induced cardiomyocytes. Gata4 overexpression also suppressed profibrotic signatures in human CFs. CONCLUSIONS: Overexpressing Gata4 in CFs may be a promising therapeutic approach for HFpEF by suppressing fibrosis and improving diastolic dysfunction
Recent advances in the bench-to-bedside translation of cancer nanomedicines
Authors: Yang Liu, Yinchao Zhang, Huikai Li, Tony Y Hu
Journal: Acta Pharmaceutica Sinica B (2024)

Cancer remains a complex and challenging medical problem, driving extensive research efforts. Despite significant progress in understanding its genetic and molecular aspects, the quest for effective treatments continues. Nanomedicines have shown great potential for revolutionizing cancer treatment by offering targeted and controlled drug delivery, reducing side effects, and improving patient outcomes. Accordingly, nanomedicines have been the focus of extensive research and development for clinical translation. As of September 2024, a search on the ClinicalTrials.gov website using the term "nanoparticles" revealed numerous ongoing and planned clinical trials. Motivated by recent advances in the field, this review explores the current frontier of cancer nanomedicine. Nanomedicines have supported chemotherapy, phototherapy and sonodynamic therapy, nucleic acid therapy, and immunotherapy. However, translating nanomedicines into practice has been challenged by complex interactions between nanoparticles and biological systems, variable permeability and retention of nanoparticles in tumors, safety concerns, difficulty achieving targeted delivery, and issues with scaling up manufacturing. Perspectives on addressing these challenges are offered. Future opportunities for cancer nanomedicines, including modifying the tumor microenvironment, integrating artificial intelligence and big data, and targeting new medical areas, are also discussed. This review underscores the potential of cancer nanomedicines to revolutionize treatment from a clinical standpoint.