bluuebunny/crossref_metadata_2025_split huggingface dataset:
The association between telomere length and non-alcoholic fatty liver disease: a prospective study
Authors: Tang Linxi , Li Dankang , Ma Yudiyang , Cui Feipeng , Wang Jianing , Tian Yaohua 
Published: November 2023

Abstract
Background
Research on the association between telomere length (TL) and incident non-alcoholic fatty liver disease (NAFLD) is limited. This study examined this association and further assessed how TL contributes to the association of NAFLD with its known risk factors.

Methods
Quantitative PCR (polymerase chain reaction) was employed to assess leucocyte telomere length. Polygenic risk score (PRS) for NAFLD, air pollution score, and lifestyle index were constructed. Cox proportional hazard models were conducted to estimate the hazard ratios (HRs) and 95% confidence intervals.

Results
Among 467,848 participants in UK Biobank, we identified 4809 NAFLD cases over a median follow-up of 12.83 years. We found that long TL was associated with decreased risk of incident NAFLD, as each interquartile range increase in TL resulted in an HR of 0.93 (95% CI 0.89, 0.96). TL partly mediated the association between age and NAFLD (proportion mediated: 15.52%). When assessing the joint effects of TL and other risk factors, the highest risk of NAFLD was found in participants with low TL and old age, low TL and high air pollution score, low TL and unfavorable lifestyle, and low TL and high PRS, compared to each reference group. A positive addictive interaction was observed between high PRS and low TL, accounting for 14.57% (2.51%, 27.14%) of the risk of NAFLD in participants with low telomere length and high genetic susceptibility.

Conclusions
Long telomere length was associated with decreased risk of NAFLD incidence. Telomere length played an important role in NAFLD.

Graphical Abstract
The oral bacterial microbiota facilitates the stratification for ulcerative colitis patients with oral ulcers
Authors: Xu Jun , Zhang Yu , Fang Xiao-Hui , Liu Yun , Huang Yi-Bo , Ke Zi-Liang , Wang Yang , Zhang Yi-Fan , Zhang Yang , Zhou Jian-Hua , Su Hui-Ting , Chen Ning , Liu Yu-Lan 
Published: November 2023

Abstract
Background
Clinically, a large part of inflammatory bowel disease (IBD) patients is complicated by oral lesions. Although previous studies proved oral microbial dysbiosis in IBD patients, the bacterial community in the gastrointestinal (GI) tract of those IBD patients combined with oral ulcers has not been profiled yet.

Methods
In this study, we enrolled four groups of subjects, including healthy controls (CON), oral ulcer patients (OU), and ulcerative colitis patients with (UC_OU) and without (UC) oral ulcers. Bio-samples from three GI niches containing salivary, buccal, and fecal samples, were collected for 16S rRNA V3-V4 region sequencing. Bacterial abundance and related bio-functions were compared, and data showed that the fecal microbiota was more potent than salivary and buccal microbes in shaping the host immune system. ~ 22 UC and 10 UC_OU 5-aminosalicylate (5-ASA) routine treated patients were followed-up for six months; according to their treatment response (a decrease in the endoscopic Mayo score), they were further sub-grouped as responding and non-responding patients.

Results
We found those UC patients complicated with oral ulcers presented weaker treatment response, and three oral bacterial genera, i.e., Fusobacterium, Oribacterium, and Campylobacter, might be connected with treatment responding. Additionally, the salivary microbiome could be an indicator of treatment responding in 5-ASA routine treatment rather than buccal or fecal ones.

Conclusions
The fecal microbiota had a strong effect on the host’s immune indices, while the oral bacterial microbiota could help stratification for ulcerative colitis patients with oral ulcers. Additionally, the oral microbiota had the potential role in reflecting the treatment response of UC patients. Three oral bacteria genera (Fusobacterium, Oribacterium, and Campylobacter) might be involved in UC patients with oral ulcers lacking treatment responses, and monitoring oral microbiota may be meaningful in assessing the therapeutic response in UC patients.
Quantitative assessment of asbestos fibers in some normal and pathological extra-abdominal tissues—a scoping review
Authors: Graziosi Francesca , Caffaro Paola , Bonetti Mattia , Roccuzzo Francesco , Rota Samantha , Boffetta Paolo , Caraballo-Arias Yohama Auxiliadora , Zunarelli Carlotta , Danilevskaia Nataliia , Violante Francesco Saverio 
Published: November 2023

Abstract

Background
Asbestos is a mineral present in nature and it has been used for years in numerous settings. Asbestos enters the bloodstream and lymphatic system mainly through breathing.

Objectives
Studies with asbestos fiber’s quantification in human tissues are scarce except for the lung. This article summarizes asbestos studies in some extra-abdominal tissues.

Methods
A scoping review of articles that quantified asbestos fibers in extra-abdominal tissues (lymph nodes, pharynx, larynx, trachea, heart) by electron microscopy (Scanning—SEM or Transmission—TEM) was performed.

Results
The 10 studies selected comprised 52 cases, out of whom 108 samples were analyzed. Mostly samples were lymph node tissues (102), followed by larynx (3) and myocardium (3). No studies were found that determined the presence of asbestos in the pharynx or trachea. The concentration of asbestos fibers detected in the lymph nodes was from 0.003 million fibers per gram of dry tissue (mfgdt) up to 7400 mfgdt, in the larynx the range was from 0.5 mfgdt up to 3.6 mfgdt, in myocardium no asbestos fibers were detected.

Discussion
The studies included were heterogeneous in terms of case and sample characteristics and analytical techniques. As subjects exposed to asbestos are often positive for fibers in thoracic lymph nodes, we suggest that whenever a human tissue sample is analyzed for asbestos presence, the relevant draining lymph node should be concomitantly studied.
Screening tools for sepsis identification in paramedicine and other emergency contexts: a rapid systematic review
Authors: De Silva Megan , Chadwick William , Naidoo Navindhra 
Published: November 2023

Abstract
Background
Sepsis is a life-threatening condition that contributes significantly to protracted hospitalisations globally. The unique positioning of paramedics and other emergency care cadres in emergency contexts enable the prospect of early identification and management of sepsis, however, a standardised screening tool still does not exist in the emergency setting. The objective of this review was to identify and recommend the most clinically ideal sepsis screening tool for emergency contexts such as emergency departments and out-of-hospital emergency contexts.

Methods
A rapid review of five databases (Medline, Embase, the Cochrane Library, CINAHL, and ProQuest Central) was undertaken, with searches performed on February 10, 2022. Covidence software was used by two authors for initial screening, and full text review was undertaken independently by each reviewer, with conflicts resolved by consensus-finding and a mediator. Systematic reviews, meta-analyses, randomised controlled trials, and prospective observational studies were eligible for inclusion. Data extraction used an a priori template and focused on sensitivity and specificity, with ROBINS-I and ROBIS bias assessment tools employed to assess risk of bias in included studies. Study details and key findings were summarised in tables. The a priori review protocol was registered on Open Science Framework (https://doi.org/10.17605/OSF.IO/3XQ5T).

Results
The literature search identified 362 results. After review, 18 studies met the inclusion criteria and were included for analysis. There were five systematic reviews, with three including meta-analysis, eleven prospective observational studies, one randomised controlled trial, and one validation study.

Conclusions
The review recognised that a paucity of evidence exists surrounding standardised sepsis screening tools in the emergency context. The use of a sepsis screening tool in the emergency environment may be prudent, however there is currently insufficient evidence to recommend a single screening tool for this context. A combination of the qSOFA and SIRS may be employed to avoid ‘practice paralysis’ in the interim. The authors acknowledge the inherent potential for publication and selection bias within the review due to the inclusion criteria.
Early-life gut microbiota in food allergic children and its impact on the development of allergic disease
Authors: Yan Xiumei , Yan Jingbin , Xiang Qiangwei , Dai Huan , Wang Yinghui , Fang Lingjuan , Huang Kaiyu , Zhang Weixi 
Published: November 2023

Abstract
Background
The prevalence of food allergies (FA) has been steadily increasing over 2 to 3 decades, showing diverse symptoms and rising severity. These long-term outcomes affect children’s growth and development, possibly linking to inflammatory bowel disease. However, the cause remains unclear. Previous studies reveal that early infancy significantly impacts FA development through gut microbiota. Yet, a consistent view on dysbiosis characteristics and its connection to future allergies is lacking. We explored how early-life gut microbiota composition relates to long-term clinical signs in children with FA through longitudinal research.

Methods
We employed high-throughput 16S rDNA gene sequencing to assess gut microbiota composition in early-life FA children in southern Zhejiang. Follow-up of clinical manifestations over 2 years allowed us to analyze the impact of early-life gut microbiota dysbiosis on later outcomes.

Results
While the diversity of gut microbiota in FA children remained stable, there were shifts in microbiota abundance. Abundant Akkermansia, Parabacteroides, Blautia, and Escherichia-Shigella increased, while Bifidobacterium and Clostridium decreased. After 2 years, two of ten FA children still showed symptoms. These two cases exhibited increased Escherichia-Shigella and reduced Bifidobacterium during early childhood. The other eight cases experienced symptom remission.

Conclusions
Our study suggests that FA and its prognosis might not correlate with early-life gut microbiota diversity. Further experiments are needed due to the small sample size, to confirm these findings.
Moving toward a contemporary classification of drug-induced kidney disease
Authors: Karimzadeh Iman , Barreto Erin F. , Kellum John A. , Awdishu Linda , Murray Patrick T. , Ostermann Marlies , Bihorac Azra , Mehta Ravindra L. , Goldstein Stuart L. , Kashani Kianoush B. , Kane-Gill Sandra L. 
Published: November 2023

AbstractDrug-induced kidney disease (DIKD) accounts for about one-fourth of all cases of acute kidney injury (AKI) in hospitalized patients, especially in critically ill setting. There is no standard definition or classification system of DIKD. To address this, a phenotype definition of DIKD using expert consensus was introduced in 2015. Recently, a novel framework for DIKD classification was proposed that incorporated functional change and tissue damage biomarkers. Medications were stratified into four categories, including “dysfunction without damage,” “damage without dysfunction,” “both dysfunction and damage,” and “neither dysfunction nor damage” using this novel framework along with predominant mechanism(s) of nephrotoxicity for drugs and drug classes. Here, we briefly describe mechanisms and provide examples of drugs/drug classes related to the categories in the proposed framework. In addition, the possible movement of a patient’s kidney disease between certain categories in specific conditions is considered. Finally, opportunities and barriers to adoption of this framework for DIKD classification in real clinical practice are discussed. This new classification system allows congruencies for DIKD with the proposed categorization of AKI, offering clarity as well as consistency for clinicians and researchers.
Estimating genome-wide DNA methylation heterogeneity with methylation patterns
Authors: Lin Pei-Yu , Chang Ya-Ting , Huang Yu-Chun , Chen Pao-Yang 
Published: November 2023

Abstract
Background
In a heterogeneous population of cells, individual cells can behave differently and respond variably to the environment. This cellular diversity can be assessed by measuring DNA methylation patterns. The loci with variable methylation patterns are informative of cellular heterogeneity and may serve as biomarkers of diseases and developmental progression. Cell-to-cell methylation heterogeneity can be evaluated through single-cell methylomes or computational techniques for pooled cells. However, the feasibility and performance of these approaches to precisely estimate methylation heterogeneity require further assessment.

Results
Here, we proposed model-based methods adopted from a mathematical framework originally from biodiversity, to estimate genome-wide DNA methylation heterogeneity. We evaluated the performance of our models and the existing methods with feature comparison, and tested on both synthetic datasets and real data. Overall, our methods have demonstrated advantages over others because of their better correlation with the actual heterogeneity. We also demonstrated that methylation heterogeneity offers an additional layer of biological information distinct from the conventional methylation level. In the case studies, we showed that distinct profiles of methylation heterogeneity in CG and non-CG methylation can predict the regulatory roles between genomic elements in Arabidopsis. This opens up a new direction for plant epigenomics. Finally, we demonstrated that our score might be able to identify loci in human cancer samples as putative biomarkers for early cancer detection.

Conclusions
We adopted the mathematical framework from biodiversity into three model-based methods for analyzing genome-wide DNA methylation heterogeneity to monitor cellular heterogeneity. Our methods, namely MeH, have been implemented, evaluated with existing methods, and are open to the research community.
Rspo2 exacerbates rheumatoid arthritis by targeting aggressive phenotype of fibroblast-like synoviocytes and disrupting chondrocyte homeostasis via Wnt/β-catenin pathway
Authors: Guo Dong , Pan Haoyan , Lu Xueying , Chen Zhong , Zhou Laixi , Chen Shuxin , Huang Jin , Liang Xinzhi , Xiao Zhisheng , Zeng Hua , Shao Yan , Qi Weizhong , Xie Denghui , Lin Chuangxin 
Published: November 2023

Abstract
Background
The aggressive phenotype of fibroblast-like synoviocytes (FLS) has been identified as a contributing factor to the exacerbation of rheumatoid arthritis (RA) through the promotion of synovitis and cartilage damage. Regrettably, there is currently no effective therapeutic intervention available to address this issue. Recent research has shed light on the crucial regulatory role of R-spondin-2 (Rspo2) in cellular proliferation, cartilage degradation, and tumorigenesis. However, the specific impact of Rspo2 on RA remains poorly understood. We aim to investigate the function and mechanism of Rspo2 in regulating the aggressive phenotype of FLS and maintaining chondrocyte homeostasis in the context of RA.

Methods
The expression of Rspo2 in knee joint synovium and cartilage were detected in RA mice with antigen-induced arthritis (AIA) and RA patients. Recombinant mouse Rspo2 (rmRspo2), Rspo2 neutralizing antibody (Rspo2-NAb), and recombinant mouse DKK1 (rmDKK1, a potent inhibitor of Wnt signaling pathway) were used to explore the role and mechanism of Rspo2 in the progression of RA, specifically in relation to the aggressive phenotype of FLS and chondrocyte homeostasis, both in vivo and in vitro.

Results
We indicated that Rspo2 expression was upregulated both in synovium and articular cartilage as RA progressed in RA mice and RA patients. Increased Rspo2 upregulated the expression of leucine-rich repeat-containing G-protein-coupled receptor 5 (LGR5), as the ligand for Rspo2, and β-catenin in FLS and chondrocytes. Subsequent investigations revealed that intra-articular administration of rmRspo2 caused striking progressive synovitis and articular cartilage destruction to exacerbate RA progress in mice. Conversely, neutralization of Rspo2 or inhibition of the Wnt/β-catenin pathway effectively alleviated experimental RA development. Moreover, Rspo2 facilitated FLS aggressive phenotype and disrupted chondrocyte homeostasis primarily through activating Wnt/β-catenin pathway, which were effectively alleviated by Rspo2-NAb or rmDKK1.

Conclusions
Our data confirmed a critical role of Rspo2 in enhancing the aggressive phenotype of FLS and disrupting chondrocyte homeostasis through the Wnt/β-catenin pathway in the context of RA. Furthermore, the results indicated that intra-articular administration of Rspo2 neutralizing antibody or recombinant DKK1 might represent a promising therapeutic strategy for the treatment of RA.
CSF biomarker analysis of ABCA7 mutation carriers suggests altered APP processing and reduced inflammatory response
Authors: Duchateau Lena , Küҫükali Fahri , De Roeck Arne , Wittens Mandy M. J. , Temmerman Joke , Weets Ilse , Timmers Maarten , Engelborghs Sebastiaan , Bjerke Maria , Sleegers Kristel 
Published: November 2023

Abstract
Background
The Alzheimer’s disease (AD) risk gene ABCA7 has suggested functions in lipid metabolism and the immune system. Rare premature termination codon (PTC) mutations and an expansion of a variable number of tandem repeats (VNTR) polymorphism in the gene, both likely cause a lower ABCA7 expression and hereby increased risk for AD. However, the exact mechanism of action remains unclear. By studying CSF biomarkers reflecting different types of AD-related pathological processes, we aim to get a better insight in those processes and establish a biomarker profile of mutation carriers.

Methods
The study population consisted of 229 AD patients for whom CSF was available and ABCA7 sequencing and VNTR genotyping had been performed. This included 28 PTC mutation and 16 pathogenic expansion carriers. CSF levels of Aβ1–42, Aβ1–40, P-tau181, T-tau, sAPPα, sAPPβ, YKL-40, and hFABP were determined using ELISA and Meso Scale Discovery assays. We compared differences in levels of these biomarkers and the Aβ ratio between AD patients with or without an ABCA7 PTC mutation or expansion using linear regression on INT-transformed data with APOE-status, age and sex as covariates.

Results
Carriers of ABCA7 expansion mutations had significantly lower Aβ1–42 levels (P = 0.022) compared with non-carrier patients. The effect of the presence of ABCA7 mutations on CSF levels was especially pronounced in APOE ε4-negative carriers. In addition, VNTR expansion carriers had reduced Aβ1–40 (P = 0.023), sAPPα (P = 0.047), sAPPβ (P = 0.016), and YKL-40 (P = 0.0036) levels.

Conclusions
Our results are suggestive for an effect on APP processing by repeat expansions given the changes in the amyloid-related CSF biomarkers that were found in carriers. The decrease in YKL-40 levels in expansion carriers moreover suggests that these patients potentially have a reduced inflammatory response to AD damage. Moreover, our findings suggest the existence of a mechanism, independent of lowered expression, affecting neuropathology in expansion carriers.
Continuous symmetry and chirality measures: approximate algorithms for large molecular structures
Authors: Alon Gil , Ben-Haim Yuval , Tuvi-Arad Inbal 
Published: November 2023

AbstractQuantifying imperfect symmetry of molecules can help explore the sources, roles and extent of structural distortion. Based on the established methodology of continuous symmetry and chirality measures, we develop a set of three-dimensional molecular descriptors to estimate distortion of large structures. These three-dimensional geometrical descriptors quantify the gap between the desirable symmetry (or chirality) and the actual one. They are global parameters of the molecular geometry, intuitively defined, and have the ability to detect even minute structural changes of a given molecule across chemistry, including organic, inorganic, and biochemical systems. Application of these methods to large structures is challenging due to countless permutations that are involved in the symmetry operations and have to be accounted for. Our approach focuses on iteratively finding the approximate direction of the symmetry element in the three-dimensional space, and the relevant permutation. Major algorithmic improvements over previous versions are described, showing increased accuracy, reliability and structure preservation. The new algorithms are tested for three sets of molecular structures including pillar[5]arene complexes with Li+, C100 fullerenes, and large unit cells of metal organic frameworks. These developments complement our recent algorithms for calculating continuous symmetry and chirality measures for small molecules as well as protein homomers, and simplify the usage of the full set of measures for various research goals, in molecular modeling, QSAR and cheminformatics.
Intranasal administration of induced pluripotent stem cell-derived cortical neural stem cell-secretome as a treatment option for Alzheimer’s disease
Authors: Mo Hyunkyung , Kim Juryun , Kim Jennifer Yejean , Kim Jang Woon , Han Heeju , Choi Si Hwa , Rim Yeri Alice , Ju Ji Hyeon 
Published: November 2023

Abstract
Background
Alzheimer’s disease (AD) is the most common neurodegenerative disorder in the elderly, resulting in gradual destruction of cognitive abilities. Research on the development of various AD treatments is underway; however, no definitive treatment has been developed yet. Herein, we present induced pluripotent stem cell (iPSC)-derived cortical neural stem cell secretome (CNSC-SE) as a new treatment candidate for AD and explore its efficacy.

Methods
We first assessed the effects of CNSC-SE treatment on neural maturation and electromagnetic signal during cortical nerve cell differentiation. Then to confirm the efficacy in vivo, CNSC-SE was administered to the 5×FAD mouse model through the nasal cavity (5 μg/g, once a week, 4 weeks). The cell-mediated effects on nerve recovery, amyloid beta (Aβ) plaque aggregation, microglial and astrocyte detection in the brain, and neuroinflammatory responses were investigated. Metabolomics analysis of iPSC-derived CNSC-SE revealed that it contained components that could exert neuro-protective effects or amplify cognitive restorative effects.

Results
Human iPSC-derived CNSC-SE increased neuronal proliferation and dendritic structure formation in vitro. Furthermore, CNSC-SE-treated iPSC-derived cortical neurons acquired electrical network activity and action potential bursts. The 5×FAD mice treated with CNSC-SE showed memory restoration and reduced Aβ plaque accumulation.

Conclusions
Our findings suggest that the iPSC-derived CNSC-SE may serve as a potential, non-invasive therapeutic option for AD in reducing amyloid infiltration and restoring memory.