tbuckley/cabot-search huggingface dataset:
Artificial intelligence scoring of liver biopsies in a phase ii trial of semaglutide in non-alcoholic steatohepatitis
Authors: Vlad Ratziu, Sven Francque, Cynthia A. Behling, Vanja Cejvanovic, Helena Cortez-Pinto, Janani S. Iyer, Niels Krarup, Quang Le, Anne-Sophie Sejling, Dina Tiniakos, Stephen A. Harrison
Journal: Hepatology (2023)

Background and Aims: Artificial intelligence–powered digital pathology offers the potential to quantify histological findings in a reproducible way. This analysis compares the evaluation of histological features of NASH between pathologists and a machine-learning (ML) pathology model. Approach and Results: This post hoc analysis included data from a subset of patients (n=251) with biopsy-confirmed NASH and fibrosis stage F1–F3 from a 72-week randomized placebo-controlled trial of once-daily subcutaneous semaglutide 0.1, 0.2, or 0.4 mg (NCT02970942). Biopsies at baseline and week 72 were read by 2 pathologists. Digitized biopsy slides were evaluated by PathAI’s NASH ML models to quantify changes in fibrosis, steatosis, inflammation, and hepatocyte ballooning using categorical assessments and continuous scores. Pathologist and ML-derived categorical assessments detected a significantly greater percentage of patients achieving the primary endpoint of NASH resolution without worsening of fibrosis with semaglutide 0.4 mg versus placebo (pathologist 58.5% vs. 22.0%, p &lt; 0.0001; ML 36.9% vs. 11.9%; p =0.0015). Both methods detected a higher but nonsignificant percentage of patients on semaglutide 0.4 mg versus placebo achieving the secondary endpoint of liver fibrosis improvement without NASH worsening. ML continuous scores detected significant treatment-induced responses in histological features, including a quantitative reduction in fibrosis with semaglutide 0.4 mg versus placebo ( p =0.0099) that could not be detected using pathologist or ML categorical assessment. Conclusions: ML categorical assessments reproduced pathologists’ results of histological improvement with semaglutide for steatosis and disease activity. ML-based continuous scores demonstrated an antifibrotic effect not measured by conventional histopathology.
Combined use of the CLivD score and FIB-4 for prediction of liver-related outcomes in the population
Authors: Fredrik Åberg, Juho Asteljoki, Ville Männistö, Panu K. Luukkonen
Journal: Hepatology (2023)

Background and Aims: A need exists for effective and practical tools to identify individuals at increased risk of liver-related outcomes (LROs) within the general population. Approach and Results: We externally validated the chronic liver disease (CLivD) score for LROs in the UK Biobank cohort. We also investigated the sequential combined use of CLivD and fibrosis-4 (FIB-4) scores. Our analysis included 369,832 adults without baseline liver disease and with available data for CLivD and FIB-4 computation. LROs reflecting compensated or decompensated liver cirrhosis or HCC were ascertained through linkages with electronic health care registries. Discriminatory performance and cumulative incidence were evaluated with competing-risk methodologies. Over a 10-year follow-up, time-dependent AUC values for LRO prediction were 0.80 for CLivD lab (including gamma-glutamyltransferase), 0.72 for CLivD non-lab (excluding laboratory values), and 0.75 for FIB-4. CLivD lab demonstrated AUC values exceeding 0.85 for liver-related death and severe alcohol-associated liver outcomes. The predictive performance of FIB-4 increased with rising CLivD scores; 10-year FIB-4 AUC values ranged from 0.60 within the minimal-risk CLivD subgroup to 0.81 within the high-risk CLivD subgroup. Moreover, in the minimal-risk CLivD subgroup, the cumulative incidence of LRO varied from 0.05% to 0.3% across low-to-high FIB-4 strata. In contrast, within the high-risk CLivD subgroup, the corresponding incidence ranged from 1.7% to 21.1% (up to 33% in individuals with FIB-4 &gt;3.25). Conclusions: The CLivD score is a valid tool for LRO risk assessment and improves the predictive performance of FIB-4. The combined use of CLivD and FIB-4 identified a subgroup where 1 in 3 individuals developed LROs within 10 years.
Menopausal hormone therapy and central nervous system tumors: Danish nested case-control study
Authors: Nelsan Pourhadi, Amani Meaidi, Søren Friis, Christian Torp-Pedersen, Lina S. Mørch
Journal: PLoS Medicine (2023)

Background Use of estrogen-containing menopausal hormone therapy has been shown to influence the risk of central nervous system (CNS) tumors. However, it is unknown how the progestin-component affects the risk and whether continuous versus cyclic treatment regimens influence the risk differently. Methods and findings Nested case-control studies within a nationwide cohort of Danish women followed for 19 years from 2000 to 2018. The cohort comprised 789,901 women aged 50 to 60 years during follow-up, without prior CNS tumor diagnosis, cancer, or contraindication for treatment with menopausal hormone therapy. Information on cumulative exposure to female hormonal drugs was based on filled prescriptions. Statistical analysis included educational level, use of antihistamines, and use of anti-asthma drugs as covariates. During follow-up, 1,595 women were diagnosed with meningioma and 1,167 with glioma. The median (first–third quartile) follow-up time of individuals in the full cohort was 10.8 years (5.0 years to 17.5 years). Compared to never-use, exposure to estrogen-progestin or progestin-only were both associated with increased risk of meningioma, hazard ratio (HR) 1.21; (95% confidence interval (CI) [1.06, 1.37] p = 0.005) and HR 1.28; (95% CI [1.05, 1.54] p = 0.012), respectively. Corresponding HRs for glioma were HR 1.00; (95% CI [0.86, 1.16] p = 0.982) and HR 1.20; (95% CI [0.95, 1.51] p = 0.117). Continuous estrogen-progestin exhibited higher HR of meningioma 1.34; (95% CI [1.08, 1.66] p = 0.008) than cyclic treatment 1.13; (95% CI [0.94, 1.34] p = 0.185). Previous use of estrogen-progestin 5 to 10 years prior to diagnosis yielded the strongest association with meningioma, HR 1.26; (95% CI [1.01, 1.57] p = 0.044), whereas current/recent use of progestin-only yielded the highest HRs for both meningioma 1.64; (95% CI [0.90, 2.98] p = 0.104) and glioma 1.83; (95% CI [0.98, 3.41] p = 0.057). Being an observational study, residual confounding could occur. Conclusions Use of continuous, but not cyclic estrogen-progestin was associated with increased meningioma risk. There was no evidence of increased glioma risk with estrogen-progestin use. Use of progestin-only was associated with increased risk of meningioma and potentially glioma. Further studies are warranted to evaluate our findings and investigate the influence of long-term progestin-only regimens on CNS tumor risk.
Antibiofilm and antithrombotic hydrogel coating based on superhydrophilic zwitterionic carboxymethyl chitosan for blood-contacting devices
Authors: Dong Uk Lee, Mukhammad Kayumov, Junghun Park, Se Kye Park, Yeongkwon Kang, Yejin Ahn, Woojin Kim, Seung Hwa Yoo, Jun-Kyu Park, Bong-Gi Kim, Yong Suk Oh, In-Seok Jeong, Dong Yun Choi
Journal: Bioactive Materials (2023)

Blood-contacting devices must be designed to minimize the risk of bloodstream-associated infections, thrombosis, and intimal lesions caused by surface friction. However, achieving effective prevention of both bloodstream-associated infections and thrombosis poses a challenge due to the conflicting nature of antibacterial and antithrombotic activities, specifically regarding electrostatic interactions. This study introduced a novel biocompatible hydrogel of sodium alginate and zwitterionic carboxymethyl chitosan (ZW@CMC) with antibacterial and antithrombotic activities for use in catheters. The ZW@CMC hydrogel demonstrates a superhydrophilic surface and good hygroscopic properties, which facilitate the formation of a stable hydration layer with low friction. The zwitterionic-functionalized CMC incorporates an additional negative sulfone group and increased negative charge density in the carboxyl group. This augmentation enhances electrostatic repulsion and facilitates the formation of hydration layer. This leads to exceptional prevention of blood clotting factor adhesion and inhibition of biofilm formation. Subsequently, the ZW@CMC hydrogel exhibited biocompatibility with tests of
A retrospective study on machine learning-assisted stroke recognition for medical helpline calls
Authors: Jonathan Wenstrup, Jakob Drachmann Havtorn, Lasse Borgholt, Stig Nikolaj Blomberg, Lars Maaloe, Michael R. Sayre, Hanne Christensen, Christina Kruuse, Helle Collatz Christensen
Journal: npj Digital Medicine (2023)

Advanced stroke treatment is time-dependent and, therefore, relies on recognition by call-takers at prehospital telehealth services to ensure fast hospitalisation. This study aims to develop and assess the potential of machine learning in improving prehospital stroke recognition during medical helpline calls. We used calls from 1 January 2015 to 31 December 2020 in Copenhagen to develop a machine learning-based classification pipeline. Calls from 2021 are used for testing. Calls are first transcribed using an automatic speech recognition model and then categorised as stroke or non-stroke using a text classification model. Call-takers achieve a sensitivity of 52.7% (95% confidence interval 49.2-56.4%) with a positive predictive value (PPV) of 17.1% (15.5-18.6%). The machine learning framework performs significantly better (p < 0.0001) with a sensitivity of 63.0% (62.0-64.1%) and a PPV of 24.9% (24.3-25.5%). Thus, a machine learning framework for recognising stroke in prehospital medical helpline calls may become a supportive tool for call-takers, aiding in early and accurate stroke recognition.
Chinese expert consensus on the diagnosis and treatment of coronary microvascular diseases (2023 Edition)
Authors: Wenqiang Chen, Mei Ni, He Huang, Hongliang Cong, Xianghua Fu, Wei Gao, Yuejin Yang, Mengyue Yu, Xiantao Song, Meilin Liu, Zuyi Yuan, Bo Zhang, Zhaohui Wang, Yan Wang, Yundai Chen, Cheng Zhang, Yun Zhang
Journal: MedComm (2023)

Abstract Since the four working groups of the Chinese Society of Cardiology issued first expert consensus on coronary microvascular diseases (CMVD) in 2017, international consensus documents on CMVD have increased rapidly. Although some of these documents made preliminary recommendations for the diagnosis and treatment of CMVD, they did not provide classification of recommendations and levels of evidence. In order to summarize recent progress in the field of CMVD, standardize the methods and procedures of diagnosis and treatment, and identify the scientific questions for future research, the four working groups of the Chinese Society of Cardiology updated the 2017 version of the Chinese expert consensus on CMVD and adopted a series of measures to ensure the quality of this document. The current consensus has raised a new classification of CMVD, summarized new epidemiological findings for different types of CMVD, analyzed key pathological and molecular mechanisms, evaluated classical and novel diagnostic technologies, recommended diagnostic pathways and criteria, and therapeutic strategies and medications, for patients with CMVD. In view of the current progress and knowledge gaps of CMVD, future directions were proposed. It is hoped that this expert consensus will further expedite the research progress of CMVD in both basic and clinical scenarios.
O‐GlcNAcylation: cellular physiology and therapeutic target for human diseases
Authors: Lin Ye, Wei Ding, Dandan Xiao, Yi Jia, Zhonghao Zhao, Xiang Ao, Jianxun Wang
Journal: MedComm (2023)

Abstract O‐linked‐β‐N‐acetylglucosamine (O‐GlcNAcylation) is a distinctive posttranslational protein modification involving the coordinated action of O‐GlcNAc transferase and O‐GlcNAcase, primarily targeting serine or threonine residues in various proteins. This modification impacts protein functionality, influencing stability, protein–protein interactions, and localization. Its interaction with other modifications such as phosphorylation and ubiquitination is becoming increasingly evident. Dysregulation of O‐GlcNAcylation is associated with numerous human diseases, including diabetes, nervous system degeneration, and cancers. This review extensively explores the regulatory mechanisms of O‐GlcNAcylation, its effects on cellular physiology, and its role in the pathogenesis of diseases. It examines the implications of aberrant O‐GlcNAcylation in diabetes and tumorigenesis, highlighting novel insights into its potential role in cardiovascular diseases. The review also discusses the interplay of O‐GlcNAcylation with other protein modifications and its impact on cell growth and metabolism. By synthesizing current research, this review elucidates the multifaceted roles of O‐GlcNAcylation, providing a comprehensive reference for future studies. It underscores the potential of targeting the O‐GlcNAcylation cycle in developing novel therapeutic strategies for various pathologies.
Guidelines for the management of Toxoplasma gondii infection and disease in patients with haematological malignancies and after haematopoietic stem-cell transplantation: guidelines from the 9th European Conference on Infections in Leukaemia, 2022
Authors: Robina Aerts, Varun Mehra, Andreas H Groll, Rodrigo Martino, Katrien Lagrou, Christine Robin, Katia Perruccio, Nicole Blijlevens, Marcio Nucci, Monica Slavin, Stéphane Bretagne, Catherine Cordonnier
Journal: The Lancet Infectious Diseases (2023)
From research to policy: still a long way to go
Authors: None The Lancet Diabetes & Endocrinology
Journal: The Lancet Diabetes & Endocrinology (2023)

As 2023 draws to a close, it is time to reflect upon and celebrate the year's most impactful research findings in diabetes and endocrinology. However, this last Editorial of the year will not highlight those findings—as rewarding as that might have been for both editors and readers. Instead, this text will mention two realities that deserve more attention than they get: the extent of research waste and the extent of research, that despite its transformative potential for impact, goes unnoticed or is dismissed by policy makers.
Neoadjuvant and adjuvant pembrolizumab plus chemotherapy in locally advanced gastric or gastro-oesophageal cancer (KEYNOTE-585): an interim analysis of the multicentre, double-blind, randomised phase 3 study
Authors: Kohei Shitara, Sun Young Rha, Lucjan S Wyrwicz, Takashi Oshima, Nina Karaseva, Mikhail Osipov, Hisateru Yasui, Hiroshi Yabusaki, Sergey Afanasyev, Young-Kyu Park, Salah-Eddin Al-Batran, Takaki Yoshikawa, Patricio Yanez, Maria Di Bartolomeo, Sara Lonardi, Josep Tabernero, Eric Van Cutsem, Yelena Y Janjigian, Do-Youn Oh, Jianming Xu, Xiao Fang, Chie-Schin Shih, Pooja Bhagia, Yung-Jue Bang
Journal: The Lancet Oncology (2023)
Bringing an end to diabetes stigma and discrimination: an international consensus statement on evidence and recommendations
Authors: Jane Speight, Elizabeth Holmes-Truscott, Matthew Garza, Renza Scibilia, Sabina Wagner, Asuka Kato, Victor Pedrero, Sonya Deschênes, Susan J Guzman, Kevin L Joiner, Shengxin Liu, Ingrid Willaing, Katie M Babbott, Bryan Cleal, Jane K Dickinson, Jennifer A Halliday, Eimear C Morrissey, Giesje Nefs, Shane O'Donnell, Anna Serlachius, Per Winterdijk, Hamzah Alzubaidi, Bustanul Arifin, Liz Cambron-Kopco, Corinna Santa Ana, Emma Davidsen, Mary de Groot, Maartje de Wit, Phyllisa Deroze, Stephanie Haack, Richard I G Holt, Walther Jensen, Kamlesh Khunti, Karoline Kragelund Nielsen, Tejal Lathia, Christopher J Lee, Bridget McNulty, Diana Naranjo, Rebecca L Pearl, Suman Prinjha, Rebecca M Puhl, Anita Sabidi, Chitra Selvan, Jazz Sethi, Mohammed Seyam, Jackie Sturt, Mythily Subramaniam, Helle Terkildsen Maindal, Virginia Valentine, Michael Vallis, Timothy C Skinner
Journal: The Lancet Diabetes & Endocrinology (2023)
Cardiac Catheterization Laboratory Management of the Comatose Adult Patient With an Out-of-Hospital Cardiac Arrest: A Scientific Statement From the American Heart Association
Authors: Jacqueline E. Tamis-Holland, Venu Menon, Nicholas J. Johnson, Karl B. Kern, Alejandro Lemor, Peter J. Mason, Mary Rodgers, Gregory W. Serrao, Demetris Yannopoulos
Journal: Circulation (2023)

Out-of-hospital cardiac arrest is a leading cause of death, accounting for ≈50% of all cardiovascular deaths. The prognosis of such individuals is poor, with &lt;10% surviving to hospital discharge. Survival with a favorable neurologic outcome is highest among individuals who present with a witnessed shockable rhythm, received bystander cardiopulmonary resuscitation, achieve return of spontaneous circulation within 15 minutes of arrest, and have evidence of ST-segment elevation on initial ECG after return of spontaneous circulation. The cardiac catheterization laboratory plays an important role in the coordinated Chain of Survival for patients with out-of-hospital cardiac arrest. The catheterization laboratory can be used to provide diagnostic, therapeutic, and resuscitative support after sudden cardiac arrest from many different cardiac causes, but it has a unique importance in the treatment of cardiac arrest resulting from underlying coronary artery disease. Over the past few years, numerous trials have clarified the role of the cardiac catheterization laboratory in the management of resuscitated patients or those with ongoing cardiac arrest. This scientific statement provides an update on the contemporary approach to managing resuscitated patients or those with ongoing cardiac arrest.
Histone‐Specific CD4<sup>+</sup> T Cell Plasticity in Active and Quiescent Systemic Lupus Erythematosus
Authors: Giuseppe A. Ramirez, Elena Tassi, Maddalena Noviello, Benedetta A. Mazzi, Luca Moroni, Lorena Citterio, Laura Zagato, Enrico Tombetti, Matteo Doglio, Elena M. Baldissera, Enrica P. Bozzolo, Chiara Bonini, Lorenzo Dagna, Angelo A. Manfredi
Journal: Arthritis & Rheumatology (2023)

Objective The aim of this study was to assess whether circulating histone‐specific T cells represent tools for precision medicine in systemic lupus erythematosus (SLE). Methods Seroprevalence of autoantibodies and HLA‐DR beta (DRB) 1 profile were assessed among 185 patients with SLE and combined with bioinformatics and literature evidence to identify HLA–peptide autoepitope couples for ex vivo detection of antigen‐specific T cells through flow cytometry. T cell differentiation and polarization was investigated in patients with SLE, patients with Takayasu arteritis, and healthy controls carrying HLA‐DRB1*03:01 and/or HLA‐DRB1*11:01. SLE Disease Activity Index 2000 and Lupus Low Disease Activity State were used to estimate disease activity and remission. Results Histone‐specific CD4 + T cells were selectively detected in patients with SLE. Among patients with a history of anti‐DNA antibodies, 77% had detectable histone‐specific T cells, whereas 50% had lymphocytes releasing cytokines or upregulating activation markers after in vitro challenge with histone peptide antigens. Histone‐specific regulatory and effector T helper (Th) 1‐, Th2‐, and atypical Th1/Th17 (Th1*)‐polarized cells were significantly more abundant in patients with SLE with quiescent disease. In contrast, total Th1‐, Th2‐, and Th1*‐polarized and regulatory T cells were similarly represented between patients and controls or patients with SLE with active versus quiescent disease. Histone‐specific effector memory T cells accumulated in the blood of patients with quiescent SLE, whereas total effector memory T cell counts did not change. Immunosuppressants were associated with expanded CD4 + histone‐specific naive T (T N ) and terminally differentiated T cells. Conclusion Histone‐specific T cells are selectively detected in patients with SLE, and their concentration in the blood varies with disease activity, suggesting that they represent innovative tools for patient stratification and therapy. image
Engineering Hyaluronic Acid Microneedles Loaded with Mn<sup>2+</sup> and Temozolomide for Topical Precision Therapy of Melanoma
Authors: Yechun Jiang, Yu Jin, Chengcheng Feng, Yayun Wu, Weinan Zhang, Liang Xiao, Zhaoyou Chu, Benjin Chen, Yan Ma, Haisheng Qian, Lingling Xu
Journal: Advanced Healthcare Materials (2023)

Topical therapy has received worldwide attention for in situ tumors owing to its higher efficacy of drug delivery. Herein, this work reports a dissolvable multifunctional hyaluronic acid microneedles (HMNs) patch coloaded with temozolomide (TMZ) and MnCl
Abstract 274: Association of Tracheal Intubation Associated Interruptions in Cardiopulmonary Resuscitation and Chest Compression Fraction During Pediatric Cardiac Arrest: A Report From the Videography in Pediatric Resuscitation Collaborative
Authors: Aaron Donoghue, Tara Neubrand, Sage Myers, Benjamin Kerrey, Karen O'Connell
Journal: Circulation (2023)

Background: Performing tracheal intubation during pediatric cardiopulmonary resuscitation has been consistently associated with worsened clinical outcomes in observational studies. One theoretical explanation for these differences is that pauses in chest compressions during attempt(s) at TI result in a decreased chest compression fraction (CCF). Objective: To examine the impact of TI attempts on CCF in children during CPR in a network of tertiary pediatric EDs. Methods: Prospective observation study from the Videography In Pediatric Resuscitation (VIPER) Collaborative. All patients receiving CPR under videorecorded conditions were eligible for enrollment. Using video review, data was collected on CPR duration, TI attempts, and the occurrence and duration of CPR interruptions during TI attempts. CCF was calculated as the total duration of CPR (100%) minus the total time of all CPR interruptions (including pauses for TI). Using nonparametric methods, univariate comparison was made between CPR events with TI-associated CPR interruptions versus CPR events without TI associated interruptions (i.e. CPR event with CPR uninterrupted during TI attempts or with no TI attempts made). Results: 111 CPR events across four sites were analyzed. The median CCF across all events was 92% (IQR 87 - 94%). At least one TI attempt was made in 40/111 (36%) of CPR events; 29/40 (75%) of these CPR events had at least 1 CPR interruption associated with TI attempt(s). There was no significant difference in CCF between CPR events with at least one TI attempt and CPR events without any TI-associated pauses (89% vs. 92%, p=0.06). Conclusions: Pediatric cardiac arrests with TI attempts made during CPR did not have significantly shorter CCF than arrests without TI attempts. Our findings refute the hypothesis that worsened clinical outcomes in children who undergo TI during CPR are due to poorer CCF, and further research should try to examine other explanations for the association between TI during CPR and poor outcomes.