bluuebunny/crossref_metadata_2025_split huggingface dataset:
A novel graph-based k-partitioning approach improves the detection of gene-gene correlations by single-cell RNA sequencing
Authors: Xu Heng , Hu Ying , Zhang Xinyu , Aouizerat Bradley E. , Yan Chunhua , Xu Ke 
Published: January 2022

Abstract
Background
Gene expression is regulated by transcription factors, cofactors, and epigenetic mechanisms. Coexpressed genes indicate similar functional categories and gene networks. Detecting gene-gene coexpression is important for understanding the underlying mechanisms of cellular function and human diseases. A common practice of identifying coexpressed genes is to test the correlation of expression in a set of genes. In single-cell RNA-seq data, an important challenge is the abundance of zero values, so-called “dropout”, which results in biased estimation of gene-gene correlations for downstream analyses. In recent years, efforts have been made to recover coexpressed genes in scRNA-seq data. Here, our goal is to detect coexpressed gene pairs to reduce the “dropout” effect in scRNA-seq data using a novel graph-based k-partitioning method by merging transcriptomically similar cells.

Results
We observed that the number of zero values was reduced among the merged transcriptomically similar cell clusters. Motivated by this observation, we leveraged a graph-based algorithm and develop an R package, scCorr, to recover the missing gene-gene correlation in scRNA-seq data that enables the reliable acquisition of cluster-based gene-gene correlations in three independent scRNA-seq datasets. The graphically partitioned cell clusters did not change the local cell community. For example, in scRNA-seq data from peripheral blood mononuclear cells (PBMCs), the gene-gene correlation estimated by scCorr outperformed the correlation estimated by the nonclustering method. Among 85 correlated gene pairs in a set of 100 clusters, scCorr detected 71 gene pairs, while the nonclustering method detected only 4 pairs of a dataset from PBMCs. The performance of scCorr was comparable to those of three previously published methods. As an example of downstream analysis using scCorr, we show that scCorr accurately identified a known cell type (i.e., CD4+ T cells) in PBMCs with a receiver operating characteristic area under the curve of 0.96.

Conclusions
Our results demonstrate that scCorr is a robust and reliable graph-based method for identifying correlated gene pairs, which is fundamental to network construction, gene-gene interaction, and cellular omic analyses. scCorr can be quickly and easily implemented to minimize zero values in scRNA-seq analysis and is freely available at https://github.com/CBIIT-CGBB/scCorr.
Characterization of non-specific lipid transfer protein (nsLtp) gene families in the Brassica napus pangenome reveals abundance variation
Authors: Liang Yu , Huang Yang , Chen Kang , Kong Xiangdong , Li Maoteng 
Published: January 2022

Abstract
Background
Brassica napus is an important agricultural species, improving stress resistance was one of the main breeding goals at present. Non-specific lipid transfer proteins (nsLTPs) are small, basic proteins which are involved in some biotic or abiotic stress responses. B. napus is susceptible to a variety of fungal diseases, so identify the BnLTPs and their expression in disease responses is very important. The common reference genome of B. napus does not contain all B. napus genes because of gene presence/absence variations between individuals. Therefore, it was necessary to search for candidate BnLTP genes in the B. napus pangenome.

Results
In the present study, the BnLTP genes were identified throughout the pangenome, and different BnLTP genes were presented among varieties. Totally, 246 BnLTP genes were identified and could be divided into five types (1, 2, C, D, and G). The classification, phylogenetic reconstruction, chromosome distribution, functional annotation, and gene expression were analyzed. We also identified potential cis-elements that respond to biotic and abiotic stresses in the 2 kb upstream regions of all BnLTP genes. RNA sequencing analysis showed that the BnLTP genes were involved in the response to Sclerotinia sclerotiorum infection. We identified 32 BnLTPs linked to blackleg resistance quantitative trait locus (QTL).

Conclusion
The identification and analysis of LTP genes in the B. napus pangenome could help to elucidate the function of BnLTP family members and provide new information for future molecular breeding in B. napus.
Impact of nutritional status on prognosis in acute myocardial infarction patients undergoing percutaneous coronary intervention
Authors: Kanda Daisuke , Ikeda Yoshiyuki , Takumi Takuro , Tokushige Akihiro , Sonoda Takeshi , Arikawa Ryo , Anzaki Kazuhiro , Kosedo Ippei , Ohishi Mitsuru 
Published: January 2022

Abstract
Background
Malnutrition affects the prognosis of cardiovascular disease. Acute myocardial infarction (AMI) has been a major cause of death around the world. Thus, we investigated the impact of malnutrition as defined by Geriatric Nutritional Risk Index (GNRI) on mortality in AMI patients.

Methods
In 268 consecutive AMI patients who underwent percutaneous coronary intervention (PCI), associations between all-cause death and baseline characteristics including malnutrition (GNRI < 92.0) and Global Registry of Acute Coronary Events (GRACE) risk score were assessed.

Results
Thirty-three patients died after PCI. Mortality was higher in the 51 malnourished patients than in the 217 non-malnourished patients, both within 1 month after PCI (p < 0.001) and beyond 1 month after PCI (p = 0.017). Multivariate Cox proportional hazards regression modelling using age, left ventricular ejection fraction and GRACE risk score showed malnutrition correlated significantly with all-cause death within 1 month after PCI (hazard ratio [HR] 7.04; 95% confidence interval [CI] 2.30–21.51; p < 0.001) and beyond 1 month after PCI (HR 3.10; 95% CI 1.70–8.96; p = 0.037). There were no significant differences in area under the receiver-operating characteristic (ROC) curve between GRACE risk score and GNRI for predicting all-cause death within 1 month after PCI (0.90 vs. 0.81; p = 0.074) or beyond 1 month after PCI (0.69 vs. 0.71; p = 0.87). Calibration plots comparing actual and predicted mortality confirmed that GNRI (p = 0.006) was more predictive of outcome than GRACE risk score (p = 0.85) beyond 1 month after PCI. Furthermore, comparison of p-value for interaction of malnutrition and GRACE risk score for all-cause death within 1 month after PCI, beyond 1 month after PCI, and the full follow-up period after PCI were p = 0.62, p = 0.64 and p = 0.38, respectively.

Conclusions
GNRI may have a potential for predicting the mortality in AMI patients especially in beyond 1 month after PCI, separate from GRACE risk score. Assessment of nutritional status may help stratify the risk of AMI mortality.
A validation study of data in the National Tonsil Surgery Register in Sweden: high agreement with medical records ensures that data can be used to monitor clinical practices and outcomes
Authors: Lundström Filip , Odhagen Erik , Alm Fredrik , Hemlin Claes , Nerfeldt Pia , Sunnergren Ola 
Published: January 2022

Abstract
Background
The ambition of the National Tonsil Surgery Register in Sweden (NTSRS) is to improve otorhinolaryngological care by monitoring trends in the clinical practices, complications, and outcomes of tonsil surgery. The NTSRS collects data from both surgeons and patients and provides the participating clinics with daily updated data on a publicly available website. On the website, national and local results can be compared and monitored. The use of NTSRS data necessitates that the data is valid, but the NTSRS has not yet been validated. With approximately half of the registered patients responding to the postoperative questionnaires, an analysis of responders and non-responders is also necessary. The aim of this study was to assess the criterion validity of NTSRS data. Another aim was to compare the characteristics and rates of complications between postoperative questionnaire responders and non-responders.

Methods
Data in the NTSRS were compared with data in electronic medical records. The 200 most recent surgeries, up to 31 Dec 2019, in each of 11 surgical units were included. Criterion validity was analysed in terms of observed agreement, Cohens kappa, Gwet’s AC1, and positive and negative agreement. The sign test was used to analyse systematic differences between the NTSRS and the medical records. Comparisons of rates between groups were made with Fisher’s exact test, the chi-square test, and Fisher’s non-parametric permutation test.

Results
A total of 1991 registrations were included in the study. All variables showed very high observed agreement ranging from 0.91 to 1.00, and all variables had AC1 values corresponding to almost perfect agreement. The analysis of questionnaire responders and non-responders showed no statistically significant differences regarding age, indication, or type of surgery. The proportion of women was higher in the responder group. The rate of reoperation due to bleeding was higher in the responder group, but there were no differences regarding other complications.

Conclusions
The results of this study show that data in the NTSRS have criterion validity. The NTSRS is thus well suited for monitoring the clinical practices and outcomes of tonsil surgery. The quality of the data also implies that the registry can be used in both clinical improvement projects and research.
Oncologic patients’ misconceptions may impede enrollment into clinical trials: a cross-sectional study
Authors: Asher Nethanel , Raphael Ari , Wolf Ido , Pelles Sharon , Geva Ravit 
Published: January 2022

Abstract
Background
Clinical trials are an essential source for advances in oncologic care, yet the enrollment rate is only 2-4%. Patients' reluctance to participate is an important barrier. This study evaluates patients' level of understanding and attitudes towards clinical trials.

Methods
This cross-sectional study was conducted in the oncology department and day care unit at the oncology division Tel Aviv Sourasky Medical Center, Israel. From January 2015 to September 2016. Two-hundred patients’ currently receiving active anti-cancer therapy at a large tertiary hospital completed an anonymous questionnaire comprised of demographic information, past experience in clinical research and basic knowledge on clinical trials.

Results
The majority of respondents did not meet the minimum knowledge level criteria. In those who replied they would decline to participate in a clinical trial, concern were related to potential assignment to the placebo arm, provision of informed consent and trust issues with their oncologist. Those with sufficient knowledge were significantly more interested in participating. Patients with past experience in clinical trials had a higher level of academic education, were less religious, had a better understanding of medical research and were inclined to participate in future research.

Conclusions
Misperceptions of clinical trials may contribute substantially to the unwillingness to participate in them.
Simple Excel and ICD-10 based dataset calculator for the Charlson and Elixhauser comorbidity indices
Authors: Prommik Pärt , Tootsi Kaspar , Saluse Toomas , Strauss Eiki , Kolk Helgi , Märtson Aare 
Published: January 2022

Abstract
Background
The Charlson and Elixhauser Comorbidity Indices are the most widely used comorbidity assessment methods in medical research. Both methods are adapted for use with the International Classification of Diseases, which 10th revision (ICD-10) is used by over a hundred countries in the world. Available Charlson and Elixhauser Comorbidity Index calculating methods are limited to a few applications with command-line user interfaces, all requiring specific programming language skills. This study aims to use Microsoft Excel to develop a non-programming and ICD-10 based dataset calculator for Charlson and Elixhauser Comorbidity Index and to validate its results with R- and SAS-based methods.

Methods
The Excel-based dataset calculator was developed using the program’s formulae, ICD-10 coding algorithms, and different weights of the Charlson and Elixhauser Comorbidity Index. Real, population-wide, nine-year spanning, index hip fracture data from the Estonian Health Insurance Fund was used for validating the calculator. The Excel-based calculator’s output values and processing speed were compared to R- and SAS-based methods.

Results
A total of 11,491 hip fracture patients’ comorbidities were used for validating the Excel-based calculator. The Excel-based calculator’s results were consistent, revealing no discrepancies, with R- and SAS-based methods while comparing 192,690 and 353,265 output values of Charlson and Elixhauser Comorbidity Index, respectively. The Excel-based calculator’s processing speed was slower but differing only from a few seconds up to four minutes with datasets including 6250–200,000 patients.

Conclusions
This study proposes a novel, validated, and non-programming-based method for calculating Charlson and Elixhauser Comorbidity Index scores. As the comorbidity calculations can be conducted in Microsoft Excel’s simple graphical point-and-click interface, the new method lowers the threshold for calculating these two widely used indices.

Trial registration
retrospectively registered.
The uptake and use of a minimum data set (MDS) for older people living and dying in care homes: a realist review
Authors: Musa Massirfufulay Kpehe , Akdur Gizdem , Brand Sarah , Killett Anne , Spilsbury Karen , Peryer Guy , Burton Jennifer Kirsty , Gordon Adam Lee , Hanratty Barbara , Towers Ann-Marie , Irvine Lisa , Kelly Sarah , Jones Liz , Meyer Julienne , Goodman Claire 
Published: January 2022

Abstract
Background
Care homes provide long term care for older people. Countries with standardised approaches to residents’ assessment, care planning and review (known as minimum data sets (MDS)) use the aggregate data to guide resource allocation, monitor quality, and for research. Less is known about how an MDS affects how staff assess, provide and review residents’ everyday care. The review aimed to develop a theory-driven understanding of how care home staff can effectively implement and use MDS to plan and deliver care for residents.

Methods
The realist review was organised according to RAMESES (Realist And Meta-narrative Evidence Synthesis: and Evolving Standards) guidelines. There were three overlapping stages: 1) defining the scope of the review and theory development on the use of minimum data set 2) testing and refining candidate programme theories through iterative literature searches and stakeholders’ consultations as well as discussion among the research team; and 3) data synthesis from stages 1 and 2. The following databases were used MEDLINE via OVID, Embase, CINAHL (Cumulative Index to Nursing and Allied Health Literature), ASSIA [Applied Social Sciences Citation Index and Abstracts]) and sources of grey literature.

Results
Fifty-one papers informed the development of three key interlinked theoretical propositions: motivation (mandates and incentives for Minimum Data Set completion); frontline staff monitoring (when Minimum Data Set completion is built into the working practices of the care home); and embedded recording systems (Minimum Data Set recording system is integral to collecting residents’ data). By valuing the contributions of staff and building on existing ways of working, the uptake and use of an MDS could enable all staff to learn with and from each other about what is important for residents’ care

Conclusions
Minimum Data Sets provides commissioners service providers and researchers with standardised information useful for commissioning planning and analysis. For it to be equally useful for care home staff it requires key activities that address the staff experiences of care, their work with others and the use of digital technology.

Registration
PROSPERO registration number CRD42020171323.
COVID-19 related outcomes among individuals with neurodegenerative diseases: a cohort analysis in the UK biobank
Authors: Hu Yihan , Yang Huazhen , Hou Can , Chen Wenwen , Zhang Hanyue , Ying Zhiye , Hu Yao , Sun Yajing , Qu Yuanyuan , Feychting Maria , Valdimarsdottir Unnur , Song Huan , Fang Fang 
Published: January 2022

Abstract
Background
An increased susceptibility to COVID-19 has been suggested for individuals with neurodegenerative diseases, but data are scarce from longitudinal studies.

Methods
In this community-based cohort study, we included 96,275 participants of the UK Biobank who had available SARS-CoV-2 test results in Public Health England. Of these, 2617 had a clinical diagnosis of neurodegenerative diseases in the UK Biobank inpatient hospital data before the outbreak of COVID-19 (defined as January 31st, 2020), while the remaining participants constituted the reference group. We then followed both groups from January 31st, 2020 to June 14th, 2021 for ascertainment of COVID-19 outcomes, including any COVID-19, inpatient care for COVID-19, and COVID-19 related death. Logistic regression was applied to estimate the association between neurogenerative disease and risks of COVID-19 outcomes, adjusted for multiple confounders and somatic comorbidities.

Results
We observed an elevated risk of COVID-19 outcomes among individuals with a neurodegenerative disease compared with the reference group, corresponding to a fully adjusted odds ratio of 2.47 (95%CI 2.25–2.71) for any COVID-19, 2.18 (95%CI 1.94–2.45) for inpatient COVID-19, and 3.67 (95%CI 3.11–4.34) for COVID-19 related death. Among individuals with a positive test result for SARS-CoV-2, individuals with neurodegenerative diseases had also a higher risk of COVID-19 related death than others (fully adjusted odds ratio 2.08; 95%CI 1.71–2.53).

Conclusion
Among UK Biobank participants who received at least one test for SARS-CoV-2, a pre-existing diagnosis of neurodegenerative disease was associated with a subsequently increased risk of COVID-19, especially COVID-19 related death.
Coexistence of Charcot-Marie-Tooth 1A and nondystrophic myotonia due to PMP22 duplication and SCN4A pathogenic variants: a case report
Authors: Nan Haitian , Wu Yunqing , Cui Shilei , Sun Houliang , Wang Jiawei , Li Ying , Meng Lingchao , Nagasaka Takamura , Wu Liyong 
Published: January 2022

Abstract
Background
Charcot-Marie-Tooth disease (CMT) is a genetically heterogeneous hereditary neuropathy, and CMT1A is the most common form; it is caused by a duplication of the peripheral myelin protein 22 (PMP22) gene. Mutations in the transient sodium channel Nav1.4 alpha subunit (SCN4A) gene underlie a diverse group of dominantly inherited nondystrophic myotonias that run the spectrum from subclinical myopathy to severe muscle stiffness, disabling weakness, or frank episodes of paralysis.

Case presentation
We describe a Chinese family affected by both CMT1A and myotonia with concomitant alterations in both the PMP22 and SCN4A genes. In this family, the affected proband inherited the disease from his father in an autosomal dominant manner. Genetic analysis confirmed duplication of the PMP22 gene and a missense c.3917G > C (p. Gly1306Ala) mutation in SCN4A in both the proband and his father. The clinical phenotype in the proband showed the combined involvement of skeletal muscle and peripheral nerves. Electromyography showed myopathic changes, including myotonic discharges. MRI revealed the concurrence of neurogenic and myogenic changes in the lower leg muscles. Sural nerve biopsies revealed a chronic demyelinating and remyelinating process with onion bulb formations in the proband. The proband’s father presented with confirmed subclinical myopathy, very mild distal atrophy and proximal hypertrophy of the lower leg muscles, pes cavus, and areflexia.

Conclusion
This study reports the coexistence of PMP22 duplication and SCN4A mutation. The presenting features in this family suggested that both neuropathy and myopathy were inherited in an autosomal dominant manner. The proband had a typical phenotype of sodium channel myotonia (SCM) and CMT1A. However, his father with the same mutations presented a much milder clinical phenotype. Our study might expand the genetic and phenotypic spectra of neuromuscular disorders with concomitant mutations.
Serum short-chain fatty acids and its correlation with motor and non-motor symptoms in Parkinson’s disease patients
Authors: Wu Gang , Jiang Zhengli , Pu Yaling , Chen Shiyong , Wang Tingling , Wang Yajing , Xu Xiaoping , Wang Shanshan , Jin Minya , Yao Yangyang , Liu Yang , Ke Shaofa , Liu Suzhi 
Published: January 2022

Abstract
Background
Parkinson’s disease (PD) is associated with enteric nervous system dysfunction and gut microbiota dysbiosis. Short-chain fatty acids (SCFAs), derived from gut microbiota, are supposed to anticipate PD pathogenesis via the pathway of spinal cord and vagal nerve or the circulatory system. However, the serum concentration of SCFAs in PD patients is poorly known. This study aims to investigate the exact level of SCFAs in PD patients and its correlation with Parkinson’s symptoms.

Methods
50 PD patients and 50 healthy controls were recruited, and their demographic and clinical characteristics were collected. The serum concentration of SCFAs was detected using a gas chromatography-mass spectrometer. SCFAs were compared between PD and control groups. The correlation between serum SCFAs and Parkinson’s symptoms and the potential effects of medications on the serum SCFAs was analyzed.

Results
Serum propionic acid, butyric acid and caproic acid were lower, while heptanoic acid was higher in PD patients than in control subjects. However, only the serum level of propionic acid was correlated with Unified Parkinson’s Disease Rating Scale (UPDRs) part III score (R = -0.365, P = 0.009), Mini-mental State Examination (MMSE) score (R = -0.416, P = 0.003), and Hamilton Depression Scale (HAMD) score (R = 0.306, P = 0.03). There was no correlation between other serum SCFAs and motor complications. The use of trihexyphenidyl or tizanidine increased the serum concentration of propionic acid.

Conclusions
Serum SCFAs are altered in PD patients, and the decrease of serum propionic acid level is correlated with motor symptoms, cognitive ability and non-depressed state. Thus, the gut microbial-derived SCFAs potentially affect Parkinson’s symptoms through the blood circulation. Propionic acid supplementation might ameliorate motor and non-motor symptoms of PD patients, although clinical trials are needed to test this hypothesis.