bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ontology-driven and weakly supervised rare disease identification from clinical notes
Authors: Dong Hang , Suárez-Paniagua Víctor , Zhang Huayu , Wang Minhong , Casey Arlene , Davidson Emma , Chen Jiaoyan , Alex Beatrice , Whiteley William , Wu Honghan 
Published: May 2023

Abstract
Background
Computational text phenotyping is the practice of identifying patients with certain disorders and traits from clinical notes. Rare diseases are challenging to be identified due to few cases available for machine learning and the need for data annotation from domain experts.

Methods
We propose a method using ontologies and weak supervision, with recent pre-trained contextual representations from Bi-directional Transformers (e.g. BERT). The ontology-driven framework includes two steps: (i) Text-to-UMLS, extracting phenotypes by contextually linking mentions to concepts in Unified Medical Language System (UMLS), with a Named Entity Recognition and Linking (NER+L) tool, SemEHR, and weak supervision with customised rules and contextual mention representation; (ii) UMLS-to-ORDO, matching UMLS concepts to rare diseases in Orphanet Rare Disease Ontology (ORDO). The weakly supervised approach is proposed to learn a phenotype confirmation model to improve Text-to-UMLS linking, without annotated data from domain experts. We evaluated the approach on three clinical datasets, MIMIC-III discharge summaries, MIMIC-III radiology reports, and NHS Tayside brain imaging reports from two institutions in the US and the UK, with annotations.

Results
The improvements in the precision were pronounced (by over 30% to 50% absolute score for Text-to-UMLS linking), with almost no loss of recall compared to the existing NER+L tool, SemEHR. Results on radiology reports from MIMIC-III and NHS Tayside were consistent with the discharge summaries. The overall pipeline processing clinical notes can extract rare disease cases, mostly uncaptured in structured data (manually assigned ICD codes).

Conclusion
The study provides empirical evidence for the task by applying a weakly supervised NLP pipeline on clinical notes. The proposed weak supervised deep learning approach requires no human annotation except for validation and testing, by leveraging ontologies, NER+L tools, and contextual representations. The study also demonstrates that Natural Language Processing (NLP) can complement traditional ICD-based approaches to better estimate rare diseases in clinical notes. We discuss the usefulness and limitations of the weak supervision approach and propose directions for future studies.
Psychometric properties of Nursing Time Management Scale (NTMS), Arabic version
Authors: Zyoud Raj’a Nayef 
Published: May 2023

AbstractDespite the presence of numerous generic time management instruments, relatively few research articles have assessed the validity and reliability of time management skills specific for the nursing profession. This study aimed at developing and validating a time management scale for nurses.Method A self-administered questionnaire was administered to 715 nurses working in hospitals and clinics in the northern region of the West Bank, Palestine. The scale was examined through exploratory factor analysis, reliability measures, and correlations with other scales.Results The scale revealed a 3-factor structure 1) organization of nursing work 2) planning and goal setting and 3) coordination of nursing work. The scale demonstrated excellent psychometric properties.Conclusions The Nursing Time Management Scale (NTMS) is a valid and reliable measure that can be used in assessing time management skills of nurses and in evaluating interventions and training modules aiming at developing nurses’ time management skills.
Sustainability of community health programme using community-based organizations: a challenge for stakeholders
Authors: Donessouné F. M. Gisèle , Sossa G. Olivier , Kouanda Seni 
Published: May 2023

AbstractA community tuberculosis programme was implemented in Burkina Faso with funding from the Global Fund to fight HIV tuberculosis and malaria. Three years after the end of the funding, it seemed necessary to examine what remains of this innovative programme, which used civil society organizations for implementation. The objective of this study was to assess the factors that influence the capacity for sustainability and the level of sustainability of the programme.Methods The case study approach was used to retrospectively identify the factors that influence the capacity for sustainability and the level of sustainability of the programme. Semi structured interviews were conducted with key informants. The data were analysed according to the theoretical frameworks of Schell and Pluye. Data was analysed using NVivo 12.Results Strong support at the national level enabled the acquisition of funding for this programme, while the instability of financial resources was a drawback to sustainability. The lack of leadership of some associations did not allow the continuation of activities after the end of the funding. The irregularity of funding and the failure to conduct a final evaluation of the programme were the weakest links in the sustainability of the programme. Thus, the analysis of our data showed precarious sustainability at the time of the study.Conclusion A well-designed community programme with a strong capacity for sustainability is not necessarily maintained after funding is withdrawn. The implementation of a community programme must ensure that it is integrated into the existing organizational system. The objectives and operating rules of the host structures must be in line with those of the programme to be implemented.
Vitamin K2 supplementation improves impaired glycemic homeostasis and insulin sensitivity for type 2 diabetes through gut microbiome and fecal metabolites
Authors: Zhang Yuntao , Liu Lin , Wei Chunbo , Wang Xuanyang , Li Ran , Xu Xiaoqing , Zhang Yingfeng , Geng Guannan , Dang Keke , Ming Zhu , Tao Xinmiao , Xu Huan , Yan Xuemin , Zhang Jia , Hu Jinxia , Li Ying 
Published: May 2023

Abstract
Background
There is insufficient evidence for the ability of vitamin K2 to improve type 2 diabetes mellitus symptoms by regulating gut microbial composition. Herein, we aimed to demonstrate the key role of the gut microbiota in the improvement of impaired glycemic homeostasis and insulin sensitivity by vitamin K2 intervention.

Methods
We first performed a 6-month RCT on 60 T2DM participants with or without MK-7 (a natural form of vitamin K2) intervention. In addition, we conducted a transplantation of the MK-7-regulated microbiota in diet-induced obesity mice for 4 weeks. 16S rRNA sequencing, fecal metabolomics, and transcriptomics in both study phases were used to clarify the potential mechanism.

Results
After MK-7 intervention, we observed notable 13.4%, 28.3%, and 7.4% reductions in fasting serum glucose (P = 0.048), insulin (P = 0.005), and HbA1c levels (P = 0.019) in type 2 diabetes participants and significant glucose tolerance improvement in diet-induced obesity mice (P = 0.005). Moreover, increased concentrations of secondary bile acids (lithocholic and taurodeoxycholic acid) and short-chain fatty acids (acetic acid, butyric acid, and valeric acid) were found in human and mouse feces accompanied by an increased abundance of the genera that are responsible for the biosynthesis of these metabolites. Finally, we found that 4 weeks of fecal microbiota transplantation significantly improved glucose tolerance in diet-induced obesity mice by activating colon bile acid receptors, improving host immune-inflammatory responses, and increasing circulating GLP-1 concentrations.

Conclusions
Our gut-derived findings provide evidence for a regulatory role of vitamin K2 on glycemic homeostasis, which may further facilitate the clinical implementation of vitamin K2 intervention for diabetes management.

Trial registration
The study was registered at https://www.chictr.org.cn (ChiCTR1800019663).
IL-6 and cfDNA monitoring throughout COVID-19 hospitalization are accurate markers of its outcomes
Authors: Bello Salvador , Lasierra Ana Belén , López-Vergara Lucía , de Diego Cristina , Torralba Laura , de Gopegui Pablo Ruiz , Lahoz Raquel , Abadía Claudia , Godino Javier , Cebollada Alberto , Jimeno Beatriz , Bello Carlota , Tejada Antonio , Torres Antoni 
Published: May 2023

Abstract
Background
Severe COVID-19 entails a dysregulated immune response, most likely inflammation related to a lack of virus control. A better understanding of immune toxicity, immunosuppression balance, and COVID-19 assessments could help determine whether different clinical presentations are driven by specific types of immune responses. The progression of the immune response and tissular damage could predict outcomes and may help in the management of patients.

Methods
We collected 201 serum samples from 93 hospitalised patients classified as moderately, severely, and critically ill. We differentiated the viral, early inflammatory, and late inflammatory phases and included 72 patients with 180 samples in separate stages for longitudinal study and 55 controls. We studied selected cytokines, P-selectin, and the tissue damage markers lactate dehydrogenase (LDH) and cell-free DNA (cfDNA).

Results
TNF-α, IL-6, IL-8, and G-CSF were associated with severity and mortality, but only IL-6 increased since admission in the critical patients and non-survivors, correlating with damage markers. The lack of a significant decrease in IL-6 levels in the critical patients and non-survivors in the early inflammatory phase (a decreased presence in the other patients) suggests that these patients did not achieve viral control on days 10–16. For all patients, lactate dehydrogenase and cfDNA levels increased with severity, and cfDNA levels increased in the non-survivors from the first sample (p = 0.002) to the late inflammatory phase (p = 0.031). In the multivariate study, cfDNA was an independent risk factor for mortality and ICU admission.

Conclusions
The distinct progression of IL-6 levels in the course of the disease, especially on days 10–16, was a good marker of progression to critical status and mortality and could guide the start of IL-6 blockade. cfDNA was an accurate marker of severity and mortality from admission and throughout COVID-19 progression.
Molecular detection of plasmid mediated blaTEM, blaCTX−M,and blaSHV genes in Extended Spectrum β-Lactamase (ESBL) Escherichia coli from clinical samples
Authors: Chaudhary Mahesh Kumar , Jadhav Indrani , Banjara Megha Raj 
Published: May 2023

Abstract
Background
Extended spectrum β-lactamases (ESBLs) are a group of beta-lactamase enzymes that confer resistance to the oxyimino-cephalosporins and monobactams. The emergence of ESBL - producing genes possesses a serious threat for treating infections since it is associated with multi-drug resistance. This study was focused to identify the ESBLs producing genes from Escherichia coli isolates from clinical samples from a referral-level tertiary care hospital in Lalitpur.

Methods
This was a cross-sectional study conducted from September 2018 to April 2020 at the Microbiology Laboratory of Nepal Mediciti Hospital. Clinical samples were processed, and culture isolates were identified and characterized following standard microbiological techniques. An antibiotic susceptibility test was performed by a modified Kirby-Bauer disc diffusion method as recommended by Clinical and Laboratory Standard Institute guidelines.Extended -spectrum beta-lactamases were phenotypically confirmed by the combined disc method. The ESBL-producing genes blaTEM, blaCTX−M and blaSHV were confirmed by PCR.

Results
Of the 1449 total E. coli isolates, 22.29% (323/1449) isolates were multi-drug resistant (MDR). Among the total MDR E. coli isolates, 66.56% (215/323) were ESBL producers. The maximum number of ESBL E. coli was isolated from urine 90.23% (194) followed by sputum 5.58% (12), swab 2.32% (5), pus 0.93% (2), and blood 0.93% (2). The antibiotic susceptibility pattern of ESBL E. coli producers showed the highest sensitivity toward tigecycline (100%) followed by polymyxin b, colistin and meropenem. Out of 215 phenotypically confirmed ESBL E. coli, only 86.51% (186) isolates were found to be positive by PCR for either blaTEM or blaCTX−M genes. Among the ESBL genotypes, the most common were blaTEM 63.4% (118) followed by blaCTX−M 36.6% (68).

Conclusion
The emergence of MDR and ESBL – producing E. coli isolates with high antibiotic – resistant rates to commonly used antibiotics and increased predominance of major gene types blaTEM is a serious concern to the clinicians and microbiologists. Periodic monitoring of antibiotic susceptibility and associated genes would help guide the rationale use of antibiotics for treating the predominant pathogen E. coli in the hospitals and healthcare facilities of the communities.
Uncovering the Fate and Risks of Intravenously Injected Prussian Blue Nanoparticles in mice by an Integrated Methodology of Toxicology, Pharmacokinetics, Proteomics, and Metabolomics
Authors: Qu Haijing , Jin Xing , Cheng Wei , Wu Dongqi , Ma Boyu , Lou Chenmei , Zheng Jian , Jing Lijia , Xue Xiangdong , Wang Yang 
Published: May 2023

Abstract
Background
Prussian blue (PB) nanoparticles (NPs) have been intensively investigated for medical applications, but an in-depth toxicological investigation of PB NPs has not been implemented. In the present study, a comprehensive investigation of the fate and risks of PB NPs after intravenous administration was carried out by using a mouse model and an integrated methodology of pharmacokinetics, toxicology, proteomics, and metabolomics.

Results
General toxicological studies demonstrated that intravenous administration of PB NPs at 5 or 10 mg/kg could not induce obvious toxicity in mice, while mice treated with a relatively high dose of PB NPs at 20 mg/kg exhibited loss of appetite and weight decrease in the first two days postinjection. Pharmacokinetic studies revealed that intravenously administered PB NPs (20 mg/kg) underwent fast clearance from blood, highly accumulated in the liver and lungs of mice, and finally cleared from tissues. By further integrated proteomics and metabolomics analysis, we found that protein expression and metabolite levels changed significantly in the liver and lungs of mice due to the high accumulation of PB NPs, leading to slight inflammatory responses and intracellular oxidative stress.

Conclusions
Collectively, our integrated experimental data imply that the high accumulation of PB NPs may cause potential risks to the liver and lungs of mice, which will provide detailed references and guidance for further clinical application of PB NPs in the future.
Hepatic fibrosis: a manifestation of the liver disease evolution in patients with Ataxia-telangiectasia
Authors: Barreto Talita Lemos Neves , de Carvalho Filho Roberto José , Shigueoka David Carlos , Fonseca Fernando Luiz Affonso , Ferreira Ariel Cordeiro , Kochi Cristiane , Aranda Carolina Sanchez , Sarni Roseli Oselka Saccardo 
Published: May 2023

Abstract
Background
Ataxia-telangiectasia (A-T) is a DNA repair disorder characterized by changes in several organs and systems. Advances in clinical protocols have resulted in increased survival of A-T patients, however disease progression is evident, mainly through metabolic and liver changes.

Objective
To identify the frequency of significant hepatic fibrosis in A-T patients and to verify the association with metabolic alterations and degree of ataxia.

Methods
This is a cross-sectional study that included 25 A-T patients aged 5 to 31 years. Anthropometric data, liver, inflammatory, lipid metabolism and glucose biomarkers (oral glucose tolerance test with insulin curve—OGTT) were collected. The Cooperative Ataxia Rating Scale was applied to assess the degree of ataxia. The following were calculated: Homeostasis Model Assessment—Insulin Resistance, Homeostasis Model Assessment—Adiponectin (HOMA-AD), Matsuda index, aspartate aminotransferase (AST): platelet ratio index, nonalcoholic fatty liver disease fibrosis score and BARD score. Liver ultrasonography and transient liver elastography by FibroScan® were performed.

Results
Significant hepatic fibrosis was observed in 5/25 (20%). Patients in the group with significant hepatic fibrosis were older (p < 0.001), had lower platelet count values (p = 0.027), serum albumin (p = 0.019), HDL-c (p = 0.013) and Matsuda index (p = 0.044); and high values of LDL-c (p = 0.049), AST (p = 0.001), alanine aminotransferase (p = 0.002), gamma-glutamyl transferase (p = 0.001), ferritin (p = 0.001), 120-min glycemia by OGTT (p = 0.049), HOMA-AD (p = 0.016) and degree of ataxia (p = 0.009).

Conclusions
A non-invasive diagnosis of significant hepatic fibrosis was observed in 20% of A-T patients associated with changes in liver enzymes, ferritin, increased HOMA-AD, and the severity of ataxia in comparison with patients without hepatic fibrosis.
Using community science data to assess the association between urbanization and the presence of invasive Aedes species in Hungary
Authors: Garamszegi László Zsolt , Soltész Zoltán , Kurucz Kornélia , Szentiványi Tamara 
Published: May 2023

Abstract
Background
Urbanization can be a significant contributor to the spread of invasive mosquito vector species, and the diseases they carry, as urbanized habitats provide access to a great density of food resources (humans and domestic animals) and offer abundant breeding sites for these vectors. Although anthropogenic landscapes are often associated with the presence of invasive mosquito species, we still have little understanding about the relationships between some of these and the built environment.

Methods
This study explores the association between urbanization level and the occurrence of invasive Aedes species, specifically Aedes albopictus, Aedes japonicus, and Aedes koreicus, in Hungary, using data from a community (or citizen) science program undertaken between 2019 and 2022.

Results
The association between each of these species and urbanized landscapes within an extensive geographic area was found to differ. Using the same standardized approach, Ae. albopictus showed a statistically significant and positive relationship with urbanization, whereas Ae. japonicus and Ae. koreicus did not.

Conclusions
The findings highlight the importance of community science to mosquito research, as the data gathered using this approach can be used to make qualitative comparisons between species to explore their ecological requirements.

Graphical Abstract
Molecular identification of non-tuberculous mycobacterial species isolated from extrapulmonary samples using real-time PCR and rpoB sequence analysis
Authors: Hashemzadeh Mohammad , Dezfuli Aram Asarehzadegan , Khosravi Azar Dokht , Bandbal Maryam Moradi , Ghorbani Atousa , Hamed Mahtab , Dezfuli Soolmaz Khandan 
Published: May 2023

AbstractTuberculosis (TB) is one of the leading causes of mortality among infectious diseases and accounts for a serious health hazard wordwide. Apart from TB, the members of non-tuberculous mycobacteria (NTM), which includes around 170 species, may also cause different diseases in humans. Therefore this study aimed to investigate the distribution of NTM strains isolated from extrapulmonary (EP) samples by Real-Time PCR and PCR-sequencing methods in Southwest Iran. Three hundred and twenty-five suspected EP samples were collected from patients referred to the referral hospitals in Ahvaz, Iran. The isolates were initially screened by acid fast staining and identified by phenotypic culture and biochemical tests. The Real-Time PCR and rpoB- based PCR methods were performed followed by sequence analysis of rpoB gene. From 124 samples, 77 (62%) were positive for NTM by culture and rpoB sequence analysis. M. fortuitum was the most commonly isolated NTM in present study. In Real-Time PCR, only 69 (55.64%) isolates showed more homology with standard NTM isolates. In general, the growing trend of EPNTM infections in Iran needs specific programs and resources to get a better diagnosis. PCR sequencing is a reliable method, it can be used for definitive identification of positive cultures for identification of NTM species.
Robust identification of regulatory variants (eQTLs) using a differential expression framework developed for RNA-sequencing
Authors: Marrella Mackenzie A. , Biase Fernando H. 
Published: May 2023

AbstractBackgroundA gap currently exists between genetic variants and the underlying cell and tissue biology of a trait, and expression quantitative trait loci (eQTL) studies provide important information to help close that gap. However, two concerns that arise with eQTL analyses using RNA-sequencing data are normalization of data across samples and the data not following a normal distribution. Multiple pipelines have been suggested to address this. For instance, the most recent analysis of the human and farm Genotype-Tissue Expression (GTEx) project proposes using trimmed means of M-values (TMM) to normalize the data followed by an inverse normal transformation.ResultsIn this study, we reasoned that eQTL analysis could be carried out using the same framework used for differential gene expression (DGE), which uses a negative binomial model, a statistical test feasible for count data. Using the GTEx framework, we identified 35 significant eQTLs (P < 5 × 10–8) following the ANOVA model and 39 significant eQTLs (P < 5 × 10–8) following the additive model. Using a differential gene expression framework, we identified 930 and six significant eQTLs (P < 5 × 10–8) following an analytical framework equivalent to the ANOVA and additive model, respectively. When we compared the two approaches, there was no overlap of significant eQTLs between the two frameworks. Because we defined specific contrasts, we identified trans eQTLs that more closely resembled what we expect from genetic variants showing complete dominance between alleles. Yet, these were not identified by the GTEx framework.ConclusionsOur results show that transforming RNA-sequencing data to fit a normal distribution prior to eQTL analysis is not required when the DGE framework is employed. Our proposed approach detected biologically relevant variants that otherwise would not have been identified due to data transformation to fit a normal distribution.