bluuebunny/crossref_metadata_2025_split huggingface dataset:
Frequency and characteristics of bacterial and viral low-grade infections of the intervertebral discs: a prospective, observational study
Authors: Senker Wolfgang , Aspalter Stefan , Radl Christian , Pichler Josef , Doppler Stefan , Weis Serge , Webersinke Christine , Wagner Helga , Hermann Philipp , Aichholzer Martin , Aufschnaiter-Hießböck Kathrin , Thomae Wolfgang , Stroh Nico , Hauser Thomas , Gruber Andreas 
Published: March 2022

Abstract
Study design
Monocentric, prospective, observational study.

Objective
The clinical relevance of bacterial colonization of intervertebral discs is controversial. This study aimed to determine a possible relationship between bacterial and viral colonization and low-grade infection of the discs.

Methods
We investigated 447 disc samples from 392 patients. Microbiological culture was used to examine the samples for bacterial growth, polymerase chain reaction (PCR) was used for detection of herpes simplex virus types 1 and 2 (HSV-1, HSV-2) and Cytomegalovirus (CMV), and histopathological analysis was used to detect signs of inflammation. The results were compared between subgroups organized according to gender, age, location of the samples, surgical approach, preoperative C-reactive protein (CRP), preoperative and 6 months postoperative Oswestry Disability Index (ODI) and Neck Disability Index (NDI), and Modic changes (MC) of the corresponding endplates. Also, we assessed the occurrence of postoperative infections within 6 months.

Results
Microbiological culture was positive in 38.78% of the analyzed intervertebral discs. Altogether, 180 bacteria were isolated. Coagulase-negative staphylococci (CONS) (23.41%) and Cutibacterium acnes (18.05%) were the most frequently detected microorganisms. None of HSV-1, HSV-2, or CMV were detected. Male patients (p = 0.00036) and cervical segments (p = 0.00001) showed higher rates of positive culture results. Ventral surgical approaches ( p < 0.001) and Type 2 MC (p = 0.0127) were significantly associated with a positive microbiological result ( p< 0.001). Neither pre- nor postoperative ODI and NDI are associated with positive culture results. In 4 (1.02%) patients, postoperative spondylodiscitis occurred.

Conclusions
With 447 segments from 392 patients, we present one of the largest studies to date. While disc degeneration caused by HSV-1, HSV-2, and CMV seems unlikely, we found positive microbiological culture results in 38.78% of all discs. The role of local skin flora and sample contamination should be the focus of further investigations.

Level of Evidence
III.
Trial registration: The study was registered at ClinicalTrials.gov (ID: NCT04712487, https://www.clinicaltrials.gov/ct2/show/study/NCT04712487).
Changing tracks: identifying and tackling bottlenecks in European rail passenger transport
Authors: Witlox Frank , Zwanikken Tim , Jehee Linde , Donners Barth , Veeneman Wijnand 
Published: March 2022

AbstractFor Europe's urban agglomerations to be economically competitive, it is vital that international destinations be easily accessible. Although much has been invested in the construction of European rail infrastructure over the past century, passenger transport by rail has not grown as fast as transport by road and air. So why do people not use international trains more, even though they have an extensive international rail network at their disposal? Based on a series of in-depth interviews with relevant public and private stakeholders and two expert meetings, we identify the main bottlenecks and constraints. In order to understand the complexity of international rail transport, we have divided the existing bottlenecks into four groups corresponding to four layers of the rail transport system: mobility services, transport services, traffic services, and the physical and digital infrastructure. We formulate concrete policy recommendations for improvements to be made in the various components of the rail transport system.
Bioinformatical analysis of the key differentially expressed genes and associations with immune cell infiltration in development of endometriosis
Authors: Chen Shengnan , Chai Xiaoshan , Wu Xianqing 
Published: March 2022

AbstractBackgroundThis study explored the key genes related to immune cell infiltration in endometriosis.ResultsThe Gene Expression Omnibus (GEO) datasets (GSE7305, GSE7307, and GSE11691), containing a total of 37 endometriosis and 42 normal tissues, were retrieved and analyzed to determine the differentially expressed genes (DEGs). Gene ontology (GO) annotations and Kyoto Encyclopedia of Genes (KEGG) analysis were performed to identify the pathways that were significantly enriched. The xCell software was used to analyze immune cell infiltration and correlation analyses were performed to uncover the relationship between key genes and immune cells. The analysis identified 1031 DEGs (581 upregulated and 450 downregulated DEGs), while GO analysis revealed altered extracellular matrix organization, collagen-containing extracellular matrix, and glycosaminoglycan binding and KEGG enrichment showed genes related to metabolic pathways, pathways in cancer, phosphatidylinositol 3-kinase-protein kinase B (PI3K-Akt) signaling, proteoglycans in cancer, and the mitogen-activated protein kinase (MAPK) signaling pathway. Furthermore, the protein–protein interaction network revealed 10 hub genes, i.e.,IL6,FN1,CDH1,CXCL8,IGF1,CDK1,PTPRC,CCNB1,MKI67, andESR1. The xCell analysis identified immune cells with significant changes in all three datasets, including CD4+and CD8+T cells, CD8+Tem, eosinophils, monocytes, Th1 cells, memory B-cells, activated dendritic cells (aDCs), and plasmacytoid dendritic cells (pDCs). These 10 hub genes were significantly associated with at least three types of immune cells.ConclusionsAberrant gene expression was related to abnormal infiltration of different immune cells in endometriosis and was associated with endometriosis development by affecting the tissue microenvironment and growth of ectopic endometrial cells.
Identifying genes with conserved splicing structure and orthologous isoforms in human, mouse and dog
Authors: Guillaudeux Nicolas , Belleannée Catherine , Blanquart Samuel 
Published: March 2022

Abstract
Background
In eukaryote transcriptomes, a significant amount of transcript diversity comes from genes’ capacity to generate different transcripts through alternative splicing. Identifying orthologous alternative transcripts across multiple species is of particular interest for genome annotators. However, there is no formal definition of transcript orthology based on the splicing structure conservation. Likewise there is no public dataset benchmark providing groups of orthologous transcripts sharing a conserved splicing structure.

Results
We introduced a formal definition of splicing structure orthology and we predicted transcript orthologs in human, mouse and dog. Applying a selective strategy, we analyzed 2,167 genes and their 18,109 known transcripts and identified a set of 253 gene orthologs that shared a conserved splicing structure in all three species. We predicted 6,861 transcript CDSs (coding sequence), mainly for dog, an emergent model species. Each predicted transcript was an ortholog of a known transcript: both share the same CDS splicing structure. Evidence for the existence of the predicted CDSs was found in external data.

Conclusions
We generated a dataset of 253 gene triplets, structurally conserved and sharing all their CDSs in human, mouse and dog, which correspond to 879 triplets of spliced CDS orthologs. We have released the dataset both as an SQL database and as tabulated files. The data consists of the 879 CDS orthology groups with their detailed splicing structures, and the predicted CDSs, associated with their experimental evidence. The 6,861 predicted CDSs are provided in GTF files. Our data may contribute to compare highly conserved genes across three species, for comparative transcriptomics at the isoform level, or for benchmarking splice aligners and methods focusing on the identification of splicing orthologs. The data is available at https://data-access.cesgo.org/index.php/s/V97GXxOS66NqTkZ.
GIF1 controls ear inflorescence architecture and floral development by regulating key genes in hormone biosynthesis and meristem determinacy in maize
Authors: Li Manfei , Zheng Yuanyuan , Cui Di , Du Yanfang , Zhang Dan , Sun Wei , Du Hewei , Zhang Zuxin 
Published: March 2022

Abstract
Background
Inflorescence architecture and floral development in flowering plants are determined by genetic control of meristem identity, determinacy, and maintenance. The ear inflorescence meristem in maize (Zea mays) initiates short branch meristems called spikelet pair meristems, thus unlike the tassel inflorescence, the ears lack long branches. Maize growth-regulating factor (GRF)-interacting factor1 (GIF1) regulates branching and size of meristems in the tassel inflorescence by binding to Unbranched3. However, the regulatory pathway of gif1 in ear meristems is relatively unknown.

Result
In this study, we found that loss-of-function gif1 mutants had highly branched ears, and these extra branches repeatedly produce more branches and florets with unfused carpels and an indeterminate floral apex. In addition, GIF1 interacted in vivo with nine GRFs, subunits of the SWI/SNF chromatin-remodeling complex, and hormone biosynthesis-related proteins. Furthermore, key meristem-determinacy gene RAMOSA2 (RA2) and CLAVATA signaling-related gene CLV3/ENDOSPERM SURROUNDING REGION (ESR) 4a (CLE4a) were directly bound and regulated by GIF1 in the ear inflorescence.

Conclusions
Our findings suggest that GIF1 working together with GRFs recruits SWI/SNF chromatin-remodeling ATPases to influence DNA accessibility in the regions that contain genes involved in hormone biosynthesis, meristem identity and determinacy, thus driving the fate of axillary meristems and floral organ primordia in the ear-inflorescence of maize.
All-cause mortality and cardiovascular events in a Spanish nonagenarian cohort according to type 2 diabetes mellitus status and established cardiovascular disease
Authors: Salinero-Fort MA , Mostaza J. , Lahoz C. , Cárdenas-Valladolid J. , Vicente-Díez J. I. , Gómez-Campelo P. , de Miguel-Yanes J. M. 
Published: March 2022

Abstract
Background
Despite the progressive aging of the population in industrialized countries, few studies have focused on the natural history of cardiovascular disease in the very old, and recommendations on prevention of cardiovascular disease in this population are lacking. We aimed to analyze all-cause mortality and cardiovascular events according to prevalent type 2 diabetes mellitus and established cardiovascular disease in nonagenarians from a Mediterranean population.

Methods
We analyzed the primary health records of all nonagenarians living in the Community of Madrid (N = 59,423) and collected data for 4 groups: Group 1, individuals without T2DM or established CVD (T2DM-, CVD-); Group 2, individuals without T2DM but with established CVD (T2DM-, CVD +); Group 3, individuals with T2DM but without established CVD (T2DM + , CVD-); and Group 4, individuals with both T2DM and established CVD (T2DM + , CVD +), taking into account the influence of sex on the outcomes. Follow-up was 2.5 years. The primary outcomes were cumulative incidence and incidence density rates for all-cause mortality, non-fatal myocardial infarction, non-fatal stroke (the first composite primary outcome [CPO1]), combined with heart failure (CPO2). We evaluated the adjusted effect of each group on all-cause mortality (Cox regression).

Results
Mean age was 93.3 ± 2.8 years (74.2% women). Hypertension, dyslipidemia, heart failure, albuminuria, and estimated glomerular filtration rate < 60 mL/min/1.73 m2 were significantly more prevalent in G4 than in the other groups (all p values < 0.001). We observed significantly higher cumulative incidence rates for all-cause mortality, CPO1, and CPO2 in participants belonging to G4 (all p values ≤ 0.001). People in G2 presented higher rates of all-cause mortality, heart failure, CPO1, and CPO2 than people in G3 (all p values ≤ 0.001). In the fully adjusted model, G4 independently predicted all-cause mortality (HR = 1.48 [95% CI, 1.40 to 1.57] vs reference G1 [p < 0.01]). In addition, significant HRs were recorded for cardiovascular disease alone (G2) and type 2 diabetes mellitus alone (G3) (1.13 and 1.14, respectively; both p values < 0.01).

Conclusions
In Spanish nonagenarians, established cardiovascular disease and type 2 diabetes mellitus conferred a modest risk of all-cause mortality. However, the simultaneous presence of both conditions conferred the highest risk of all-cause mortality.
Periconceptional folic acid supplementation is a risk factor for childhood asthma: a case-control study
Authors: Chu Shuyuan , Zhang Jun 
Published: March 2022

Abstract
Background
Several studies found an association between periconceptional folic acid supplementation and the risk of childhood asthma. But the epidemiologic evidence is still inconsistent and the underlying biological mechanisms remain unclear.

Methods
We conducted a hospital-based case-control study on childhood asthma with 548 cases and 816 normal controls in Shanghai, China. Mothers of the asthma children were asked about folic acid supplementation before and during pregnancy. Unconditional logistic regression models were employed to control for potential confounders.

Results
Periconceptional folic acid supplementation was associated with an increased risk of childhood asthma after adjusting for potential confounders (adjusted OR = 1.28 [95% CI 1.14–1.43]). Moreover, the adjusted OR varied by the timing of starting folic acid supplementation: before gestation: 1.31 [95% CI 1.01–1.70]; in the 1st month of gestation: 1.09 [95% CI 0.96–1.23]; and after the 1st month of gestation: 1.90 [95% CI 1.56–2.30]. We further found that the adjusted OR was the highest when periconceptional folic acid supplementation lasted more than 6 months (< 4 months: 1.21 [95% CI 1.07–1.37]; 4–6 months: 1.06 [95% CI 0.88–1.27]; > 6 months: 1.75 [95% CI 1.35–2.27]).

Conclusions
Periconceptional folic acid supplementation was associated with an increased risk of childhood asthma in offspring. Further research on this issue is warranted.
Increased expression of Nrf2 and elevated glucose uptake in pheochromocytoma and paraganglioma with SDHB gene mutation
Authors: Kamai Takao , Murakami Satoshi , Arai Kyoko , Nishihara Daisaku , Uematsu Toshitaka , Ishida Kazuyuki , Kijima Toshiki 
Published: March 2022

Abstract
Background
Pheochromocytomas (PCC) and paragangliomas (PGL) are catecholamine-producing neuroendocrine tumors. According to the World Health Organization Classification 2017, all PCC/PGL are considered to have malignant potential. There is growing evidence that PCC/PGL represent a metabolic disease that leads to aerobic glycolysis. Cellular energy metabolism involves both transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) and succinate dehydrogenase (SDH) subtypes, but the association of these substances with PCC/PGL is largely unknown.

Methods
We investigated SDHB gene mutation and protein expressions for SDHB and Nrf2 in surgical specimens from 29 PCC/PGL. We also assessed preoperative maximum standard glucose uptake (SUVmax) on [18F]fluorodeoxy-glucose positron emission tomography and mRNA levels for Nrf2.

Results
Among 5 PCC/PGL with a PASS Score ≥ 4 or with a moderately to poorly differentiated type in the GAPP Score, 4 were metastatic and found to be SDHB mutants with homogeneous deletion of SDHB protein. SDHB mutants showed a higher expression of Nrf2 protein and a higher preoperative SUVmax than non-SDHB mutants with a PASS < 4 or a well-differentiated GAPP type. Furthermore, protein expression of Nrf2 was positively associated with preoperative SUVmax. The Nrf2 mRNA level positively correlated with malignant phenotype, higher expression for Nrf2 protein and SDHB gene mutant, but negatively correlated with expression for SDHB protein. There was also a positive correlation between Nrf2 mRNA level and SUVmax.

Conclusion
These results suggest that activation of Nrf2 and elevated metabolism play roles in PCC/PGL with malignant potential that have SDHB gene mutation and SDHB deficiency.
Current situation of pediatric clinical trials in China: focus on trials for drug marketing application and administrative approval
Authors: Song Lin , Jia Yuntao , Ran Sujuan , Li Bin , Xu Jin , Huo Bennian , Yin Nange , Ai Maolin , Liu Yao 
Published: March 2022

Abstract
Background
Research and development of pediatric drug faces many difficulties and pediatric clinical trials remain a challenge. Since 2011, a series of measures have been taken to encourage research, development of drugs for pediatric patients in China. In this study, we analyzed pediatric clinical trials conducted in China to provide reference for research and development of pediatric drugs and formulation of relevant policies.

Methods
We conducted a cross-sectional observational study of pediatric trials registered in the Drug Trial Registration and Information Publication Platform before Oct. 31, 2021. All trials that recruited children (under 18 years old as defined in China) were retrieved and general characteristics of the trials and the research drugs were extracted and analyzed. The data were extracted and statistically analyzed by excel 2010 and SPSS 22.0, respectively.

Results
There were 588 registered pediatric clinical trials, which accounted for 3.94% of the total registered trials. The overall average annual growth rate of the number of trials from 2013 to 2020 was 14.47% (P < 0.01). Of the 588 trials included, there were 312 trials (53.06%) with only children as subjects, 127 trials (21.60%) with research drugs only for children use, and the median of target subject number was 320 with the range of 8 to 600,000. The sponsors and the principal investigators were mainly located in the eastern and northern China. 325 trials were vaccine trials, and the dosage form was mainly injection. There were 98 non-vaccine biological product trials (mainly injections), 135 chemical compound drug trials (mainly tablets), 30 traditional Chinese medicine/natural drugs (mainly granules). Indications of the non-vaccine drugs were mainly diseases of the blood and blood-forming organs and certain disorders involving the immune mechanism.

Conclusion
The number of pediatric clinical trials in China has increased these years. To further promote pediatric clinical trials and motivate pediatric appropriate drug marketing application and administrative approval, conducting large pediatric clinical trials, further development of dosage forms suitable for children with special attention to neonates and prematurity, and improving uneven geographical distribution of sponsors and researchers are the current challenges.
Experiences of new diagnoses among HIV-positive persons: implications for public health
Authors: Owusu Adobea Yaa 
Published: March 2022

AbstractBackgroundReady acceptance of experiences of new diagnoses among HIV-positive persons is a known personal and public health safety-net. Its beneficial effects include prompt commencement and sustenance of HIV-positive treatment and care, better management of transmission risk, and disclosure of the HIV-positive status to significant others. Yet, no known study has explored this topic in Ghana; despite Ghana’s generalised HIV/AIDS infection rate. Existing studies have illuminated the effects of such reactions on affected significant others; not the infected.MethodsThis paper studied qualitatively the experiences of new diagnoses among 26 persons living with HIV/AIDS. Sample selection was random, from two hospitals in a district in Ghana heavily affected by HIV/AIDS. The paper applied the Hopelessness Theory of Depression.ResultsAs expected, the vast majority of respondents experienced the new diagnoses of their HIV-positive infection with a myriad of negative psychosocial reactions, including thoughts of committing suicide. Yet, few of them received the news with resignation. For the vast majority of respondents, having comorbidities from AIDS prior to the diagnosis primarily shaped their initial reactions to their diagnosis. The respondents’ transitioning to self-acceptance of their HIV-positive status was mostly facilitated by receiving counselling from healthcare workers.ConclusionsAlthough the new HIV-positive diagnosis was immobilising to most respondents, the trauma faded, paving the way for beneficial public health actions. The results imply the critical need for continuous education on HIV/AIDS by public health advocates, using mass media, particularly, TV. Healthcare workers in VCTs should empathise with persons who experience new diagnoses of their HIV-positive status.
Research on exercise fatigue estimation method of Pilates rehabilitation based on ECG and sEMG feature fusion
Authors: Li Dujuan , Chen Caixia 
Published: March 2022

Abstract
Purpose
Surface electromyography (sEMG) is vulnerable to environmental interference, low recognition rate and poor stability. Electrocardiogram (ECG) signals with rich information were introduced into sEMG to improve the recognition rate of fatigue assessment in the process of rehabilitation.

Methods
Twenty subjects performed 150 min of Pilates rehabilitation exercise. Twenty subjects performed 150 min of Pilates rehabilitation exercise. ECG and sEMG signals were collected at the same time. Aftering necessary preprocessing, the classification model of improved particle swarm optimization support vector machine base on sEMG and ECG data fusion was established to identify three different fatigue states (Relaxed, Transition, Tired). The model effects of different classification algorithms (BPNN, KNN, LDA) and different fused data types were compared.

Results
IPSO-SVM had obvious advantages in the classification effect of sEMG and ECG signals, the average recognition rate was 87.83%. The recognition rates of sEMG and ECG fusion feature classification models were 94.25%, 92.25%, 94.25%. The recognition accuracy and model performance was significantly improved.

Conclusion
The sEMG and ECG signal after feature fusion form a complementary mechanism. At the same time, IPOS-SVM can accurately detect the fatigue state in the process of Pilates rehabilitation. On the same model, the recognition effect of fusion of sEMG and ECG(Relaxed: 98.75%, Transition:92.25%, Tired:94.25%) is better than that of only using sEMG signal or ECGsignal. This study establishes technical support for establishing relevant man–machine devices and improving the safety of Pilates rehabilitation.