bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multiomics links global surfactant dysregulation with airflow obstruction and emphysema in COPD
Authors: Hristova Ventzislava A. , Watson Alastair , Chaerkady Raghothama , Glover Matthew S. , Ackland Jodie , Angerman Bastian , Belfield Graham , Belvisi Maria G. , Burke Hannah , Cellura Doriana , Clark Howard W. , Etal Damla , Freeman Anna , Heinson Ashley I. , Hess Sonja , Hühn Michael , Hall Emily , Mackay Alex , Madsen Jens , McCrae Christopher , Muthas Daniel , Novick Steven , Ostridge Kristoffer , Öberg Lisa , Platt Adam , Postle Anthony D. , Spalluto C. Mirella , Vaarala Outi , Wang Junmin , Staples Karl J. , Wilkinson Tom M.A. ,   on behalf of the MICA II Study group
Published: December 2022

RationalePulmonary surfactant is vital for lung homeostasis as it reduces surface tension to prevent alveolar collapse and provides essential immune-regulatory and antipathogenic functions. Previous studies demonstrated dysregulation of some individual surfactant components in COPD. We investigated relationships between COPD disease measures and dysregulation of surfactant components to gain new insights into potential disease mechanisms.MethodsBronchoalveolar lavage proteome and lipidome were characterised in ex-smoking mild/moderate COPD subjects (n=26) and healthy ex-smoking (n=20) and never-smoking (n=16) controls using mass spectrometry. Serum surfactant protein analysis was performed.ResultsTotal phosphatidylcholine, phosphatidylglycerol, phosphatidylinositol, surfactant protein (SP)-B, SP-A and SP-D concentrations were lower in COPDversuscontrols (log2fold change (log2FC) −2.0, −2.2, −1.5, −0.5, −0.7 and −0.5 (adjusted p<0.02), respectively) and correlated with lung function. Total phosphatidylcholine, phosphatidylglycerol, phosphatidylinositol, SP-A, SP-B, SP-D, napsin A and CD44 inversely correlated with computed tomography small airways disease measures (expiratory to inspiratory mean lung density) (r= −0.56, r= −0.58, r= −0.45, r= −0.36, r= −0.44, r= −0.37, r= −0.40 and r= −0.39 (adjusted p<0.05)). Total phosphatidylcholine, phosphatidylglycerol, phosphatidylinositol, SP-A, SP-B, SP-D and NAPSA inversely correlated with emphysema (% low-attenuation areas): r= −0.55, r= −0.61, r= −0.48, r= −0.51, r= −0.41, r= −0.31 and r= −0.34, respectively (adjusted p<0.05). Neutrophil elastase, known to degrade SP-A and SP-D, was elevated in COPDversuscontrols (log2FC 0.40, adjusted p=0.0390), and inversely correlated with SP-A and SP-D. Serum SP-D was increased in COPDversushealthy ex-smoking volunteers, and predicted COPD status (area under the curve 0.85).ConclusionsUsing a multiomics approach, we demonstrate, for the first time, global surfactant dysregulation in COPD that was associated with emphysema, giving new insights into potential mechanisms underlying the cause or consequence of disease.
Robust and accurate prediction of self-interacting proteins from protein sequence information by exploiting weighted sparse representation based classifier
Authors: Li Yang , Hu Xue-Gang , You Zhu-Hong , Li Li-Ping , Li Pei-Pei , Wang Yan-Bin , Huang Yu-An 
Published: December 2022

AbstractBackgroundSelf-interacting proteins (SIPs), two or more copies of the protein that can interact with each other expressed by one gene, play a central role in the regulation of most living cells and cellular functions. Although numerous SIPs data can be provided by using high-throughput experimental techniques, there are still several shortcomings such as in time-consuming, costly, inefficient, and inherently high in false-positive rates, for the experimental identification of SIPs even nowadays. Therefore, it is more and more significant how to develop efficient and accurate automatic approaches as a supplement of experimental methods for assisting and accelerating the study of predicting SIPs from protein sequence information.ResultsIn this paper, we present a novel framework, termed GLCM-WSRC (gray level co-occurrence matrix-weighted sparse representation based classification), for predicting SIPs automatically based on protein evolutionary information from protein primary sequences. More specifically, we firstly convert the protein sequence into Position Specific Scoring Matrix (PSSM) containing protein sequence evolutionary information, exploiting the Position Specific Iterated BLAST (PSI-BLAST) tool. Secondly, using an efficient feature extraction approach, i.e., GLCM, we extract abstract salient and invariant feature vectors from the PSSM, and then perform a pre-processing operation, the adaptive synthetic (ADASYN) technique, to balance the SIPs dataset to generate new feature vectors for classification. Finally, we employ an efficient and reliable WSRC model to identify SIPs according to the known information of self-interacting and non-interacting proteins.ConclusionsExtensive experimental results show that the proposed approach exhibits high prediction performance with 98.10% accuracy on the yeast dataset, and 91.51% accuracy on the human dataset, which further reveals that the proposed model could be a useful tool for large-scale self-interacting protein prediction and other bioinformatics tasks detection in the future.
RLFDDA: a meta-path based graph representation learning model for drug–disease association prediction
Authors: Zhang Meng-Long , Zhao Bo-Wei , Su Xiao-Rui , He Yi-Zhou , Yang Yue , Hu Lun 
Published: December 2022

Abstract
Background
Drug repositioning is a very important task that provides critical information for exploring the potential efficacy of drugs. Yet developing computational models that can effectively predict drug–disease associations (DDAs) is still a challenging task. Previous studies suggest that the accuracy of DDA prediction can be improved by integrating different types of biological features. But how to conduct an effective integration remains a challenging problem for accurately discovering new indications for approved drugs.

Methods
In this paper, we propose a novel meta-path based graph representation learning model, namely RLFDDA, to predict potential DDAs on heterogeneous biological networks. RLFDDA first calculates drug–drug similarities and disease–disease similarities as the intrinsic biological features of drugs and diseases. A heterogeneous network is then constructed by integrating DDAs, disease–protein associations and drug–protein associations. With such a network, RLFDDA adopts a meta-path random walk model to learn the latent representations of drugs and diseases, which are concatenated to construct joint representations of drug–disease associations. As the last step, we employ the random forest classifier to predict potential DDAs with their joint representations.

Results
To demonstrate the effectiveness of RLFDDA, we have conducted a series of experiments on two benchmark datasets by following a ten-fold cross-validation scheme. The results show that RLFDDA yields the best performance in terms of AUC and F1-score when compared with several state-of-the-art DDAs prediction models. We have also conducted a case study on two common diseases, i.e., paclitaxel and lung tumors, and found that 7 out of top-10 diseases and 8 out of top-10 drugs have already been validated for paclitaxel and lung tumors respectively with literature evidence. Hence, the promising performance of RLFDDA may provide a new perspective for novel DDAs discovery over heterogeneous networks.
Genetic diversity and forensic application of Y-filer STRs in four major ethnic groups of Pakistan
Authors: Ikram Muhammad Salman , Mehmood Tahir , Rakha Allah , Akhtar Sareen , Khan Muhammad Imran Mahmood , Al-Qahtani Wedad Saeed , Safhi Fatmah Ahmed , Hadi Sibte , Wang Chuan-Chao , Adnan Atif 
Published: December 2022

Abstract17 Y-chromosomal STRs which are part of the Yfiler Amplification Kit were investigated in 493 unrelated Pakistani individuals belonging to the Punjabi, Sindhi, Baloch, and Pathan ethnic groups. We have assessed the forensic parameters and population genetic structure for each group. Among the 493 unrelated individuals from four ethnic groups (128 Baloch, 122 Pathan, 108 Punjabi, and 135 Sindhi), 82 haplotypes were observed with haplotype diversity (HD) of 0.9906 in Baloch, 102 haplotypes with HD value of 0.9957 in Pathans, 80 haplotypes with HD value of 0.9924 in Punjabi, and 105 haplotypes with HD value of 0.9945 in the Sindhi population. The overall gene diversity for Baloch, Pathan, Punjabi, and Sindhi populations was 0.6367, 0.6479, 0.6657, and 0.6112, respectively. The results had shown us that Pakistani populations do not have a unique set of genes but share the genetic affinity with regional (Central Asia and Northern India) populations. The observed low gene diversity (heterozygosity) values may be because of endogamy trends and this observation is equally supported by the results of forensic parameters which are mostly static across 4 combinations (minimal STRs, extended 11 Y-STRs, Powerplex 12 Y System, and Yfiler 17 Y-STRs) of STRs in these four populations.
Mutation of gdpS gene induces a viable but non-culturable state in Staphylococcus epidermidis and changes in the global transcriptional profile
Authors: Zhu Tao , Wang Wei , Wang Han , Zhao Yanfeng , Qu Di , Wu Yang 
Published: December 2022

Abstract
Background
In the genome of staphylococci, only the gdpS gene encodes the conserved GGDEF domain, which is the characteristic of diguanylate cyclases. In our previous study, we have demonstrated that the gdpS gene can modulate biofilm formation by positively regulating the expression of ica operon in Staphylococcus epidermidis. Moreover, this regulation seems to be independent of the c-di-GMP signaling pathway and the protein-coding function of this gene. Therefore, the biological function of the gdpS gene remains to be further investigated.

Results
In the present study, it was observed that mutation of the gdpS gene induced S. epidermidis to enter into a presumed viable but nonculturable state (VBNC) after cryopreservation with glycerol. Similarly, when moved from liquid to solid culture medium, the gdpS mutant strain also exhibited a VBNC state. Compared with the wild-type strain, the gdpS mutant strain autolyzed more quickly during storage at 4℃, indicating its increased susceptibility to low temperature. Transcriptional profiling analysis showed that the gdpS mutation affected the transcription of 188 genes (92 genes were upregulated and 96 genes were downregulated). Specifically, genes responsible for glycerol metabolism were most markedly upregulated and most of the altered genes in the mutant strain are those involved in nitrogen metabolism. In addition, the most significantly downregulated genes included the betB gene, whose product catalyzes the synthesis of glycine betaine and confers tolerance to cold.

Conclusion
The preliminary results suggest that the gdpS gene may participate in VBNC formation of S. epidermidis in face of adverse environmental factors, which is probably achieved by regulating expression of energy metabolism genes. Besides, the gdpS gene is critical for S. epidermidis to survive low temperature, and the underlying mechanism may be partly explained by its influence on expression of betB gene.
De novo transcriptome sequencing of Impatiens uliginosa and the analysis of candidate genes related to spur development
Authors: Li Yang , Wei Chun-Mei , Li Xin-Yi , Meng Dan-Chen , Gu Zhi-Jia , Qu Su-Ping , Huang Mei-Juan , Huang Hai-Quan 
Published: December 2022

Abstract
Background
Spur, a structure capable of producing and storing nectar, not only plays a vital role in the pollination process but also promotes the rapid diversification of some plant lineages, which is considered a key innovation in plants. Spur is the focus of many studies, such as evolution and ecological hypothesis, but the current understanding of spur development is limited. High-throughput sequencing of Impatiens uliginosa was carried out to study the molecular mechanism of its spur development, which is believed to provide some insights into the spur development of Impatiens.

Results
Transcriptomic sequencing and analysis were performed on spurs and limbs of I. uliginosa at three developmental stages. A total of 47.83 Gb of clean data were obtained, and 49,716 unigene genes were assembled. After comparison with NR, Swiss-Prot, Pfam, COG, GO and KEGG databases, a total of 27,686 genes were annotated successfully. Through comparative analysis, 19,356 differentially expressed genes were found and enriched into 208 GO terms and 146 KEGG pathways, among which plant hormone signal transduction was the most significantly enriched pathway. One thousand thirty-two transcription factors were identified, which belonged to 33 TF families such as MYB, bHLH and TCP. Twenty candidate genes that may be involved in spur development were screened and verified by qPCR, such as SBP, IAA and ABP.

Conclusions
Transcriptome data of different developmental stages of spurs were obtained, and a series of candidate genes related to spur development were identified. The importance of genes related to cell cycle, cell division, cell elongation and hormones in spur development was clarified. This study provided valuable information and resources for understanding the molecular mechanism of spur development in Impatiens.
Gastrodin improves neuroinflammation-induced cognitive dysfunction in rats by regulating NLRP3 inflammasome
Authors: Zheng Xue , Gong Taowu , Tang Chunchun , Zhong Yuanping , Shi Lu , Fang Xu , Chen Dongqin , Zhu Zhaoqiong 
Published: December 2022

AbstractNeuroinflammation is the main pathological mechanism of cognitive dysfunction caused by neurodegenerative diseases, and effective preventive and therapeutic measures are not available. We predicted the key targets of gastrodin’s effects upon neuroinflammation through Network Pharmacology and molecular docking. Then the predicted targets were used to study how gastrodin affected cognitive dysfunction triggered by lipopolysaccharide-induced neuroinflammation in rats and its mechanisms. Three-month-old male rats were intraperitoneally injected with lipopolysaccharide for 3 days (d), 7 d and 14 d respectively. Gastrodin improved learning and memory ability of rats with neuroinflammation. Lipopolysaccharide enhanced the levels of pro-inflammatory cytokines, such as TNF-α, IL-1β and IL-6, in rat hippocampus, which could be reversed by gastrodin. Gastrodin also inhibited the activation of microglia. Our findings suggested that gastrodin exerted neuroprotective effects in rats with neuroinflammation by impacting the TLR4-NF-kB-NLRP3 pathway. Therefore, gastrodin may be a potential therapeutic agent for neuroinflammation-induced cognitive dysfunction.
Case study research and causal inference
Authors: Green Judith , Hanckel Benjamin , Petticrew Mark , Paparini Sara , Shaw Sara 
Published: December 2022

AbstractCase study methodology is widely used in health research, but has had a marginal role in evaluative studies, given it is often assumed that case studies offer little for making causal inferences. We undertook a narrative review of examples of case study research from public health and health services evaluations, with a focus on interventions addressing health inequalities. We identified five types of contribution these case studies made to evidence for causal relationships. These contributions relate to: (1) evidence about system actors’ own theories of causality; (2) demonstrative examples of causal relationships; (3) evidence about causal mechanisms; (4) evidence about the conditions under which causal mechanisms operate; and (5) inference about causality in complex systems. Case studies can and do contribute to understanding causal relationships. More transparency in the reporting of case studies would enhance their discoverability, and aid the development of a robust and pluralistic evidence base for public health and health services interventions. To strengthen the contribution that case studies make to that evidence base, researchers could: draw on wider methods from the political and social sciences, in particular on methods for robust analysis; carefully consider what population their case is a case ‘of’; and explicate the rationale used for making causal inferences.
How stressful was the COVID-19 pandemic for residents specializing in family practice?. A study of stressors and psychological well-being of physicians in further training specializing in family practice (GP trainees) within a pandemic context
Authors: von Oltersdorff-Kalettka Anna-Maria , Meinel Janina , Voigt Karen , Mundt Thomas , Bleckwenn Markus , Bergmann Antje , Gottschall Mandy 
Published: December 2022

Abstract
Background
The coronavirus pandemic poses many challenges for medical personnel. During the first phase of the pandemic, psychological stress became increasingly apparent. This was a complex and difficult situation, especially for physician residents specializing in family practice (GP trainees), who were not yet able to draw on years of practical experience. In this context, the Kompetenzzentrum Weiterbildung Allgemeinmedizin Sachsen (Competence Center for Continuing Education in General Medicine Saxony) (KWASa) developed a survey on how to deal with the concerns and challenges perceived at the time. The purpose of the study was to obtain information on psychological well-being in the pandemic context, as well as on expectations, fears, and protective measures in everyday work. The aim was to identify stress factors for general practice (GP) trainees during a pandemic situation to be able to consider the support needs in the design of future residency training programs, especially for GP trainees.

Methods
An online questionnaire was distributed from May 5, 2020 to June 4, 2020 among GP trainees enrolled in KWASa since 2018. The questionnaire consisted of standardized items, which were evaluated descriptively, and open-ended items with free-text answers, which were evaluated according to the principle of qualitative content analysis.

Results
The results show the relevance of the topic as 61% of respondents indicated that they were concerned about the coronavirus. Most GP trainees also gave an affirmative response regarding emotional challenges. In this context, various stressors could be identified within both the professional and personal environments. There were four particularly salient factors: (1) the fear of infecting one’s family as well as patients with the SARS-CoV-2 virus; (2) missing or insufficiently existing protective measures; (3) an increased need for consultation due to unpredictable patient behavior as well as uncertainties in patient treatment; and (4) communication difficulties within the collegial environment.

Conclusions
The study aimed to identify the support needs of GP trainees in crisis situations such as the COVID-19 pandemic. The results of the survey can be used for the development of suitable continuing education programs for physicians in further training.
The postoperative prognosis of older intertrochanteric fracture patients as evaluated by the Chang reduction quality criteria
Authors: He Miao , Liu Jian , Deng Xu , Zhang Xiaoxing 
Published: December 2022

AbstractObjectiveThe aim of this study was to investigate the relationship between the Chang reduction quality criteria (CRQC) and the outcome of intertrochanteric fractures in older adults according to follow-up time.MethodsThis was a retrospective analysis of 389 older adult patients with intertrochanteric fractures treated surgically from January 2019 to June 2021, including 130 males and 259 females aged 84.6 (77.5–89.7) years. Patient survival was determined by telephone as the time between admission to hospital for fracture and death or until the study deadline (June 1, 2022). According to the CRQC, the patients were divided into the Poor, Acceptable, and Excellent groups. Univariate and multivariate Cox proportional hazard models were used to assess the association between CRQC and all-cause mortality in older adult intertrochanteric fractures at 1 year and the total follow-up time. Further subgroup analysis was performed according to different clinical and biological characteristics to improve the accuracy of the results.ResultsThe mortality rates were 24.7% and 15.4% at 1 year and the total follow-up time, respectively. Both at one year and the total follow-up time, the mortality of the CRQC-Excellent group was significantly lower than that of the CRQC-Acceptable group (p.adj < 0.05) and the CRQC-Poor group (p.adj < 0.05). After multifactor adjustment, CRQC grades of Acceptable and Poor were independent risk factors affecting the overall and 1-year mortality. In addition, advanced age, ≥ 1 comorbidities, ASA 3 + 4, and prolonged preoperative waiting time were independent risk factors for survival at the total follow-up time. At 1 year, only ASA 3 + 4 and prolonged preoperative waiting time were independent risk factors for survival. Subgroup analysis according to different characteristics at the total follow-up time and at one year showed that in most subgroups, a decrease in the CRQC grade was significantly associated with an increase in all-cause mortality (p for trend < 0.05).ConclusionsThis study highlights that CRQC grades of Acceptable and Poor are associated with increased all-cause mortality in older adult intertrochanteric fractures. We should attempt to achieve good reduction of these fractures.
Determinants of post-stroke depression among stroke survivors at University of Gondar Hospital, Northwest Ethiopia: a case-control study
Authors: Fantu Ephrem , Hailu Workagegnehu , Bekele Nebiyu , Tsegaye Tewodros , Tadesse Melaku , Asres Mezgebu Silamsaw 
Published: December 2022

Abstract
Background
Stroke is one of the most common causes of disability among adults. Post-stroke depression (PSD) is a frequent neuropsychiatric complication in stroke patients. Despite the increasing prevalence of stroke, there is a paucity of data on PSD and its determinants among stroke survivors in developing countries like Ethiopia. We aim to assess the factors associated with PSD in survivors of stroke.

Method
A hospital-based unmatched case-control study was conducted during the period of February to July 2020 at University of Gondar Hospital among stroke survivors. Study subjects were recruited consecutively. Socio-demographic and clinical data were obtained from patients’ interviews and medical record reviews. A diagnosis of PSD was made using the Patient Health Questionnaire (PHQ-9). EpiData version 3.1 was used to enter data, and SPSS version 26 was used to analyze it. Bivariate and multivariate logistic regressions were fitted to identify associated variables. The adjusted odds ratio (AOR) with 95% confidence interval (CI) and p-value 0.05 were used to determine the significance of the association.

Result
A total of 240 stroke survivors were included in the study (80 cases and 160 controls). The mean age was 60.8 years (SD ± 14.3) with an equal sex distribution. Variables statistically associated with PSD were male gender (AOR = 3.5, 95% CI: 1.64-7.46 C, P-value = 0.001), subcortical location of the largest lesion (AOR = 2.42, 95% CI: 1.06–5.56, p-value = 0.036), severity of the stroke (AOR = 52.34, 95% CI:10.64-256.87, p-value = 0.000), physical disability (AOR = 5.85. 95% CI:1.94–17.65, p-value = 0.002), previous history of stroke or transient ischemic attack (AOR = 5.90, 95% CI:2.04–17.10, p-value = 0.001) and ischemic heart disease (AOR = 9.97, 95% CI:3.4-29.22, p-value = 0.000).

Conclusion
Important factors in the occurrence of PSD in this study include prior history of stroke, physical disability, severity of the stroke, subcortical location of the lesion, male gender, and ischemic heart disease. Stroke patients with such factors need routine screening for PSD, particularly in LMICs where there is uncoordinated post-stroke care, a shortage of neurologists and mental health practitioners.