bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of four novel acute‐on‐chronic liver failure clusters with distinct clinical trajectories and mortality using machine learning methods
Authors: Verma Nipun , Garg Pratibha , Valsan Arun , Roy Akash , Mishra Saurabh , Kaur Parminder , Rathi Sahaj , De Arka , Premkumar Madhumita , Taneja Sunil , Singh Virendra , Dhiman Radha K. , Duseja Ajay K. , Kamath Patrick 
Published: September 2024

SummaryBackground and AimsMachine learning (ML) can identify the hidden patterns without hypothesis in heterogeneous diseases like acute‐on‐chronic live failure (ACLF). We employed ML to describe and predict yet unknown clusters in ACLF.MethodsClinical data of 1568 patients with ACLF from a tertiary care centre (2015–2023) were subjected to distance‐, density‐ and model‐based clustering algorithms. Final model was selected on best cluster separation, viz. Silhouette width and Dunn's index (for distance‐ or density‐based algorithms) and minimum BIC (for model‐based algorithms). Cluster assignments, patient trajectories and survival were analysed through inferential statistics. Supervised ML models were trained in 70% data that predicted clusters in remaining 30% data followed by an temporal validation.ResultsThe cohort was male‐predominant (87%), aged 44.3 years, with alcohol‐associated hepatitis (62.9%) and survival of 50.5%. Due to poor performance of distance‐ and density‐based algorithms and better explainability, the latent class model (LCM) was selected for exploration. LCM revealed four clusters with distinct trajectories, reversibility and survival (independent of MELD, CLIF‐C ACLF and AARC scores). Cluster1 had patients with none/one organ failure and highest reversibility. Cluster2 had females with viral hepatitis and two organ failures. More‐than‐one acute precipitant, severity, infections, organ failures and irreversibility escalated from clusters 1 to 4. Circulatory and renal failures critically influenced cluster assignments. Incorporating clusters to CLIF‐C ACLF, infection and ACLF definition improved the discriminative accuracy of CLIF‐C‐ACLF by 11%. Extreme gradient boost and decision trees could predict clusters with AUCs of 0.989 (0.979–0.995) and 0.875 (0.865–0.890). MELD, CLIF‐C‐OF, haemoglobin, lactate, CLIF‐C‐ACLF and ALT were critical variables for cluster prediction. Clusters with distinct survival were documented in a temporal validation cohort.ConclusionsML for the first time could identify clusters with distinct phenotypes, trajectories and outcomes in ACLF. Stratification into clusters can address heterogeneity, guide prognosis, recruitment in trials, resource allocation and liver transplant discussions in ACLF.
Meta‐analysis: Risk of lymphoma in patients with inflammatory bowel disease in population‐based cohort studies
Authors: Zamani Mohammad , Alizadeh‐Tabari Shaghayegh , Murad Mohammad Hassan , Singh Siddharth , Ananthakrishnan Ashwin N. , Malekzadeh Reza , Talley Nicholas J. 
Published: September 2024

SummaryBackgroundThere are inconsistencies in the results of the studies investigating the association between inflammatory bowel disease (IBD) and lymphoma.AimsThe aim of this study is to systematically appraise the risk of lymphoma development in patients with IBD.MethodsWe searched Embase, PubMed and Scopus from inception to 30 April 2024 to identify population‐based cohort studies that evaluated the risk of lymphoma in patients with IBD in comparison with those without IBD. We carried out random‐effects meta‐analyses and estimated pooled relative risks (RRs) with 95% confidence intervals (CIs).ResultsWe identified 23 eligible studies reporting 2078 lymphoma events in 656,731 patients with IBD. Patients with IBD had 30% higher odds of lymphoma (RR = 1.30 [95% CI: 1.21–1.40]). The risk of developing both Hodgkin's lymphoma (nine studies, RR = 1.29 [95% CI: 1.06–1.53]) and non‐Hodgkin's lymphoma (16 studies, RR = 1.31 [95% CI: 1.20–1.42]) was increased in patients with IBD (p for interaction = 0.881). The increased risk of lymphoma was observed in both Crohn's disease (17 studies, RR = 1.54 [95% CI: 1.27–1.80]) and ulcerative colitis (20 studies, RR = 1.22 [95% CI: 1.09–1.35]) (p for interaction = 0.026). Meta‐regression demonstrated that mean age of patients, study year, mean study follow‐up duration, and percentages of immunomodulators and biologics use did not influence study outcome.ConclusionsThe risk of lymphoma is only modestly increased in patients with IBD, with Crohn's disease having a slightly higher risk than ulcerative colitis. In IBD, there appears to be no difference between the risks of Hodgkin's and non‐Hodgkin's lymphoma.
Attitudes on affirmative action targeted to help Black and Hispanic individuals: The roles of knowledge, race, and perceived discrimination
Authors: Umanzor Marden J. , Guerrero David J. Reyna , Osborne Randall E. , McField Ariel A. , Oberle Crystal D. 
Published: September 2024

AbstractThis study explored factors affecting affirmative action attitudes. Undergraduates at a Hispanic‐Serving Institution completed measures assessing support for Black‐targeted and Hispanic‐targeted affirmative action, perceived discrimination against Blacks and Hispanics, and demographic information. Prior to completing these measures, some participants were randomly assigned to read 10 facts about current racial inequities. An ANOVA revealed a marginally significant effect of condition (with greater affirmative action support by participants who read facts about racial inequities vs. the control condition), a significant effect of participant race (with greater affirmative action support by Black and Hispanic vs. White participants), and a significant interaction between participant and target race (with greater support of Hispanic‐targeted vs. Black‐targeted affirmative action by White and Hispanic participants, but no difference in support for Hispanic‐targeted vs. Black‐targeted affirmative action by Black participants). Regression analyses revealed that affirmative action support was significantly associated with a Democrat affiliation, a Black or Hispanic race, and perceived discrimination against Blacks and Hispanics. These findings are consistent with social dominance theory (whereby group status threat may influence Hispanic affirmative action support) and the altruism‐born‐of‐suffering theory (whereby adverse discriminatory experiences of Blacks may lead to greater empathy and support for affirmative action).
The effectiveness of the OECD Guidelines' NCP procedure
Authors: Mayar Aziza , Maas Karen 
Published: September 2024

AbstractThe OECD Guidelines for Multinational Enterprises have become increasingly relevant in the debate on the role of business in society. This instrument for responsible business conduct (RBC) is considered to be unique due to its implementation mechanism, the National Contact Point (NCP) procedure. The NCP procedure applies a pragmatic stakeholder engagement approach to contribute to the effectiveness of the OECD Guidelines. However, little is known about the effects of the NCP procedure. To fill this gap, this study provides insights into the ex‐post effects of the Dutch NCP procedure on solving non‐compliance issues, the RBC performance of MNEs, and societal impact. This study developed a framework of different layers of effects. It used this framework to gather and analyze empirical data through interviews with parties that have participated in non‐compliance procedures. The effects found are mainly related to solving issues, while the effects on RBC within MNEs and their societal impact seem limited. Based on the findings, this study concludes that the full potential of the OECD Guidelines remains unrealized in most of the investigated cases.
Improved platelet separation performance from whole blood using an acoustic fluidics system
Authors: Sakai Kazuko , Ohara Shuta , Tanaka Junko , Suda Kenichi , Muramatsu Takamichi , Uematsu Chihiro , Tsutani Yasuhiro , Mitsudomi Tetsuya , Nishio Kazuto 
Published: September 2024

AbstractThis study investigated the effectiveness of acoustic separation for platelet analysis in patients with non–small‐cell lung cancer (NSCLC), comparing it with traditional centrifugation methods. In total, 10 patients with NSCLC and 10 healthy volunteers provided peripheral blood samples, which were processed using either acoustic separation or centrifugation to isolate platelets. The study included whole transcriptome analysis of platelets, peripheral blood mononuclear cells, and tumor tissue samples, employing hierarchical clustering and Gene Ontology analysis to explore gene expression differences. Acoustic separation proved more efficient than centrifugation in terms of platelet yield, recovery rate, and RNA yield. Gene expression profiles of platelets from patients with NSCLC showed distinct patterns compared with healthy volunteers, indicating tumor‐influenced alterations. Gene Ontology analysis revealed enrichment in pathways associated with platelet activation and the tumor microenvironment. This finding indicates the potential of acoustic isolation in platelet separation and its relevance in understanding the unique gene expression profile of platelets in patients with NSCLC. The findings of this study suggested that platelets from cancer patients separated by acoustic techniques exhibited tumor‐specific alterations and provided new insights into the diagnosis of cancer in platelet analysis systems in clinical practice.
Identification of ENO‐1 positive extracellular vesicles as a circulating biomarker for monitoring of Ewing sarcoma
Authors: Uotani Koji , Fujiwara Tomohiro , Ueda Koji , Yoshida Aki , Iwata Shintaro , Morita Takuya , Kiyono Masahiro , Kunisada Toshiyuki , Takeda Ken , Hasei Joe , Yoshioka Yusuke , Ochiya Takahiro , Ozaki Toshifumi 
Published: September 2024

AbstractThe lack of circulating biomarkers for tumor monitoring is a major problem in Ewing sarcoma management. The development of methods for accurate tumor monitoring is required, considering the high recurrence rate of drug‐resistant Ewing sarcoma. Here, we describe a sensitive analytical technique for tumor monitoring of Ewing sarcoma by detecting circulating extracellular vesicles secreted from Ewing sarcoma cells. Proteomic analysis of Ewing sarcoma cell‐derived extracellular vesicles identified 564 proteins prominently observed in extracellular vesicles from three Ewing sarcoma cell lines. Among these, CD99, SLC1A5, and ENO‐1 were identified on extracellular vesicles purified from sera of patients with Ewing sarcoma before treatment but not on extracellular vesicles from those after treatment and healthy individuals. Notably, not only Ewing sarcoma‐derived extracellular vesicles but also Ewing sarcoma cells demonstrated proteomic expression of CD99 and ENO‐1 on their surface membranes. ENO‐1+CD63+ extracellular vesicle detection was reduced after tumor resection while both CD99+CD63+ and ENO‐1+CD63+ extracellular vesicles were detected in serum from Ewing sarcoma‐bearing mice. Finally, the accuracy of liquid biopsy targeting these candidates was assessed using extracellular vesicles from the sera of patients with Ewing sarcoma. Elevated ENO‐1+CD81+ extracellular vesicles in the serum of patients before treatments distinguished patients with Ewing sarcoma from healthy individuals with an area under the curve value of 0.92 (P < 0.001) and reflected the tumor burden in patients with Ewing sarcoma during multidisciplinary treatments. Collectively, circulating ENO‐1+CD81+ extracellular vesicle detection could represent a novel tool for tumor monitoring of Ewing sarcoma.
Common principles of macrophage biology in blood–tissue barriers
Authors: Hiraga Shin‐ichiro , Masuda Takahiro 
Published: September 2024

AbstractBlood–tissue barriers play crucial roles in specialized tissues such as the central nervous system (CNS), eye, testis, and placenta. Tissue‐resident macrophages in these tissues are indispensable for maintaining tissue homeostasis and responding to pathological conditions. Recent advances in high‐throughput and high‐dimensional single‐cell analysis techniques, coupled with fate‐mapping tools, have revealed a remarkable diversity of tissue‐resident macrophages at the blood–tissue barrier. However, while comprehensive expression profiling has revealed the heterogeneity of macrophages within individual tissues, the commonalities of macrophages across anatomically similar structures like blood–tissue barriers remain poorly understood. This review focuses on the diversity and functional specialization of macrophages in tissues with blood–tissue barriers, highlighting recent insights into their anatomical distribution, developmental origins, phenotypic characteristics, and roles in maintaining tissue homeostasis. These findings may deepen our understanding of macrophage adaptation mechanisms in tissues with blood–tissue barriers, potentially leading to improved therapies for related disorders. Furthermore, examining the similarities and differences of macrophages across tissues may elucidate the molecular underpinnings of tissue‐specific adaptation mechanisms and functional specialization.
Living With Spasticity During the COVID‐19 Pandemic: A Qualitative Study of Patient, Carer and Physician Experiences
Authors: Sakel Mohamed , Saunders Karen , Faruqui Rafey , Keene Jamie , Wilkinson David 
Published: September 2024

ABSTRACTBackgroundApproximately 4.4 million people in England (8% of the total population) are living with a long‐term neurological condition. Within this group of vulnerable individuals, there will be individuals living with severe spasticity that requires regular outpatient treatment with botulinum toxin injection. The closure of outpatient spasticity services during the pandemic impacted individuals who required spasticity treatment and their carers, as well as the specialist clinicians responsible for service delivery.ObjectivesWe aimed to gain insight into the experiences of individuals living with spasticity, their carers and a clinical spasticity service lead during the pandemic, and to reflect on potential learning for the future.MethodsA qualitative study was designed using semi‐structured interviews conducted by telephone. Participants comprised patients living with a long‐term neurological condition who attended outpatient spasticity clinics before the start of the pandemic in England, primary carers who accompanied patients attending these clinics and a clinical spasticity service lead. Data were audio recorded, transcribed, anonymised and coded. Data analysis utilised the One Sheet of Paper thematic approach to identify themes, which were discussed and analysed by the interdisciplinary research team and two patient and carer participants.ResultsOut of the 11 participants recruited, aged 36–77 years, seven comprised people living with spasticity related to a long‐term neurological condition, three were carers and one was a clinical spasticity service lead. Six participants were male and five were female. Among the participants, four were stroke survivors, two were living with spinal cord injury and one was living with multiple sclerosis. Analysis revealed six major themes: experience of living with spasticity during the pandemic; impact of the pandemic on patient, carer and clinician health; access to and experience of outpatient clinic appointments; coping strategies during the pandemic; system improvements; and learning from the pandemic period.ConclusionThese findings contribute research knowledge to a very limited research knowledge base and suggest that there is scope for improving system and service delivery through the allocation of research funding to senior clinicians working in this specialist area.
Quality Assessment of Cryopreserved Peripheral Blood Stem Cell Products: Evaluation of Two Methods for Flow Cytometric Viability Testing
Authors: Rimac Vladimira , Bojanić Ines , Škifić Marijana , Dabelić Sanja , Golubić Ćepulić Branka 
Published: September 2024

ABSTRACTIntroductionThe standard flow cytometry method for viability testing using 7‐aminoactinomycin D (7‐AAD) determines cells in necrosis and late apoptosis. The colony‐forming unit (CFU) assay, which evaluates the proliferation ability of HSCs, is also used in graft quality assessment despite known deficiencies that make this assay impractical in routine clinical settings. The aim was to compare the effectiveness of the flow cytometry 7‐AAD/annexin V method with the 7‐AAD method in assessing the quality of HSCs in autologous and allogeneic peripheral blood stem cell (PBSC) products.MethodsThirty autologous and 30 allogeneic fresh and thawed cryopreserved PBSC products were included in this study. The viability of HSCs was determined using the 7‐AAD method and 7‐AAD/annexin V method on a flow cytometer, while their clonogenic capacity was assessed by CFU assay.ResultsThere was an excellent correlation for CD34+ cell viability between the 7‐AAD and the 7‐AAD/annexin V method for fresh samples (Rs = 0.930, p < 0.001) and a good correlation for thawed PBSC samples (Rs = 0.739, p < 0.001). Excellent correlation was observed for post‐thaw CD34+ cell recovery between the two methods for viability (Rs = 0.980, p < 0.001). Statistical analysis showed a weak correlation between CFU‐GM recovery and CD34+ cell recovery, regardless of which viability testing method was used (7‐AAD method p = 0.021, Rs = 0.298; 7‐AAD/annexin V method p = 0.029, Rs = 0.282).ConclusionsResults of this study showed that in the quality assessment of cryopreserved PBSC product viability, the 7‐AAD/annexin V method had no added value compared to the 7‐AAD method, which was suitable enough for routine quality control of cryopreserved autologous and allogeneic PBSC samples.
Application of Antioxidant‐ and Antimicrobial‐Rich Extracts From Hass Avocado Pulp in the Development of Chitosan/Gelatin‐Based Active Packaging Films for Raw Meat Preservation
Authors: Tran Thi Tuong Vi , Dang Thanh‐Thuy , Lam Nguyen Duy , Nguyen Quoc‐Duy , Tran Tuan Sang , Nguyen Thi‐Van‐Linh 
Published: September 2024

ABSTRACTIn the present study, the ethanolic extracts derived from Hass avocado pulp were observed to exhibit exceptional bioactive qualities and demonstrate bactericidal efficacy against a wide range of microorganisms, encompassing both gram‐positive and gram‐negative bacteria, as well as fungi. Therefore, this work aimed to develop a biodegradable active film by incorporating the Hass avocado extracts into chitosan/gelatin‐based film (HGCF) for the preservation of beef and pork. The study reveals that the chitosan/gelatin‐based film (GCF) and HGCF exhibit significant water stability and absorption capabilities. HGCF offered the synergy of antimicrobial properties of Hass avocado extracts and high swelling in water of chitosan/gelatin blend to absorb liquid discharged from fresh meat for prolonged storage. HGCF demonstrated a significant effectiveness in controlling microbial density in comparison to uncoated samples and samples coated with plain gelatin/chitosan film. In detail, HGCF was able to partially eliminate Staphylococcus aureus and Escherichia coli during storage, resulting in the densities after 14 days that were similar to those of uncoated meat samples after 6 days. These results demonstrate the potential of HGCF as active packaging for food preservation and advance the sustainable production and preservation of meat products.
An Experimental Study to Optimize Neuromuscular Blockade Protocols in Cynomolgus Macaques: Monitoring, Doses, and Antagonism
Authors: Letscher Hélène , Lemaitre Julien , Burban Emma , Le Grand Roger , Bruhns Pierre , Relouzat Francis , Gouel‐Chéron Aurélie 
Published: September 2024

ABSTRACTBackgroundNeuromuscular blocking agents (NMBAs) are a crucial component of anesthesia and intensive care through the relaxation of skeletal muscles. They can lead to adverse reactions such as postoperative residual neuromuscular block. Only one agent is capable of an instant block reversal in deep block situations, but is restricted to aminosteroid agents. Among animal models, non‐human primates are an essential model for a great diversity of human disease models. The main objective of this study was to establish a model for NMBA monitoring with current available drugs before testing new reversal agents.MethodsSeven healthy male cynomolgus macaques were randomly assigned to this study. Experiments using macaques were approved by the local ethical committee (CEtEA #44). All animals were anesthetized according to institutional guidelines, with ketamine and medetomidine, allowing IV line placement and tracheal intubation. Anesthesia was maintained with isoflurane. Either rocuronium bromine (with or without sugammadex reversal) or atracurium besylate was evaluated. Monitoring was performed with two devices, TOF‐Watch and ToFscan, measuring the T4/T1 and the T4/Tref ratios, respectively. Nonparametric Mann–Whitney statistical analyses were done when indicated.ResultsNMBA monitoring required adaptation compared to humans, such as stimulus intensity and electrode placement, to be efficient and valid in cynomolgus macaques. When administered, both NMBAs induced deep and persistent neuro‐muscular block at equivalent doses to clinical doses in humans. The rocuronium‐induced profound neuromuscular block could be reversed using the cyclodextrin sugammadex as a reversal agent. We report no adverse effects in these models by clinical observation, blood chemistry, or complete blood count.ConclusionThese results support the use of non‐human primate models for neuromuscular block monitoring. This represented the first step before the forthcoming testing of new NMBA‐reversal agents.
Characteristics of the Serum Microbiota and Circulating Metabolites in Cynomolgus Monkeys With Spontaneous Type 2 Diabetes Mellitus
Authors: Tian Chaoyang , Yang Qunhui , Lv Haizhou , Yue Feng 
Published: September 2024

ABSTRACTBackgroundType 2 diabetes mellitus (T2DM) is widely recognized as a serious global public health concern with a substantial economic burden on patients, their families, and society. Accumulating evidence suggests that an etiologic role for serum microbiota and circulating metabolites in the pathogenesis of T2DM. This study aims to characterize the serum microbiota and circulating metabolites in cynomolgus monkeys with spontaneous T2DM, and provide a reference for the diagnosis and treatment of clinical T2DM.MethodsWe collected serum samples of the 14 cynomolgus monkeys (15–20 years old, male) for serum microbiota analysis by 16S rRNA gene V3‐V4 region amplicon sequencing and circulating metabolites analysis by ultra‐high‐performance liquid chromatography–tandem mass spectrometry, of which seven were spontaneous T2DM cynomolgus monkeys and seven were healthy controls.ResultsOur results showed that the serum microbiota abundance and diversity were significantly increased in cynomolgus monkeys with spontaneous T2DM compared to healthy controls, the phyla of Cyanobacteria and Chloroflexi and the genera of Lactobacillus, rhodobacter and collinsella were also significantly increased. A total of 114 serum differentially expressed metabolites (DEMs) were identified, of which 22 were selected as potential biomarkers candidates related to spontaneous T2DM in cynomolgus monkeys by multivariate data analysis. In addition, serum levels of total SCFAs, acetate, butyrate, caproate, isobutyrate, and isovalerate were also significantly increased in the present study. The correlation network analyses have selected certain key DEMs, such as D‐Psicose, 4‐Oxoproline, D‐Glutamine, and Hydroxyphenyllactic acid, which may serve as potential biomarkers for distinguishing between T2DM and healthy controls.ConclusionOur results provide preliminary insights on perturbed serum microbiota and circulating metabolites of cynomolgus monkeys with spontaneous T2DM. These findings would be useful to develop microbiota‐based strategies for T2DM prevention and control.