bluuebunny/crossref_metadata_2025_split huggingface dataset:
Engagement in different sport disciplines during university years and risk of locomotive syndrome in older age: J-Fit+ Study
Authors: Shen Shaoshuai , Suzuki Koya , Kohmura Yoshimitsu , Fuku Noriyuki , Someya Yuki , Naito Hisashi 
Published: March 2021

Abstract
Background
Among former Olympic-level athletes, engagement in different sport disciplines has been associated with mortality risk in subsequent years. However, limited evidence is available on whether engagement in different sport disciplines at a young age is associated with locomotive syndrome (LS) risk later in life. This study examined the relationship between engagement in different sport disciplines during university years and LS risk in older age among former university athletes.

Methods
Participants were 274 middle-aged and 294 older men alumni who graduated from a school of physical education in Japan. LS risk was defined as answering “yes” to any of the Loco-check questions. Data on university sports club membership were collected using questionnaires. University clubs were classified into three groups of cardiovascular intensity (low, moderate, high), following the classification system of sport disciplines by the American College of Cardiology. This classification considers the static and dynamic components of an activity, which correspond to the estimated percent of maximal voluntary contraction reached and maximal oxygen uptake achieved, respectively. University clubs were grouped based on the risk of bodily collision (no, yes) and extent of physical contact (low, moderate, high). Relationships between engagement in different sport disciplines and LS risk were analyzed using Cox proportional hazards models, and adjusted for age, height, weight, joint disease, habitual exercise, and smoking and drinking status.

Results
Adjusted hazard ratios and 95% confidence intervals associated with the low, moderate, and high cardiovascular intensity sports were 1.00 (reference), 0.48 (0.22–1.06, P = 0.070), and 0.44 (0.20–0.97, P = 0.042) in older men, respectively; however, there was no significant association between these parameters among middle-aged men. Engagement in sports associated with physical contact and collision did not affect LS risk in either group.

Conclusions
Engagement in sports associated with high cardiovascular intensity during university years may reduce the risk of LS in later life. Encouraging young people to participate in such activities might help reduce LS prevalence among older populations.
SLIDR and SLOPPR: flexible identification of spliced leader trans-splicing and prediction of eukaryotic operons from RNA-Seq data
Authors: Wenzel Marius A. , Müller Berndt , Pettitt Jonathan 
Published: March 2021

Abstract
Background
Spliced leader (SL) trans-splicing replaces the 5′ end of pre-mRNAs with the spliced leader, an exon derived from a specialised non-coding RNA originating from elsewhere in the genome. This process is essential for resolving polycistronic pre-mRNAs produced by eukaryotic operons into monocistronic transcripts. SL trans-splicing and operons may have independently evolved multiple times throughout Eukarya, yet our understanding of these phenomena is limited to only a few well-characterised organisms, most notably C. elegans and trypanosomes. The primary barrier to systematic discovery and characterisation of SL trans-splicing and operons is the lack of computational tools for exploiting the surge of transcriptomic and genomic resources for a wide range of eukaryotes.

Results
Here we present two novel pipelines that automate the discovery of SLs and the prediction of operons in eukaryotic genomes from RNA-Seq data. SLIDR assembles putative SLs from 5′ read tails present after read alignment to a reference genome or transcriptome, which are then verified by interrogating corresponding SL RNA genes for sequence motifs expected in bona fide SL RNA molecules. SLOPPR identifies RNA-Seq reads that contain a given 5′ SL sequence, quantifies genome-wide SL trans-splicing events and predicts operons via distinct patterns of SL trans-splicing events across adjacent genes. We tested both pipelines with organisms known to carry out SL trans-splicing and organise their genes into operons, and demonstrate that (1) SLIDR correctly detects expected SLs and often discovers novel SL variants; (2) SLOPPR correctly identifies functionally specialised SLs, correctly predicts known operons and detects plausible novel operons.

Conclusions
SLIDR and SLOPPR are flexible tools that will accelerate research into the evolutionary dynamics of SL trans-splicing and operons throughout Eukarya and improve gene discovery and annotation for a wide range of eukaryotic genomes. Both pipelines are implemented in Bash and R and are built upon readily available software commonly installed on most bioinformatics servers. Biological insight can be gleaned even from sparse, low-coverage datasets, implying that an untapped wealth of information can be retrieved from existing RNA-Seq datasets as well as from novel full-isoform sequencing protocols as they become more widely available.
CytoGLMM: conditional differential analysis for flow and mass cytometry experiments
Authors: Seiler Christof , Ferreira Anne-Maud , Kronstad Lisa M. , Simpson Laura J. , Le Gars Mathieu , Vendrame Elena , Blish Catherine A. , Holmes Susan 
Published: March 2021

AbstractBackgroundFlow and mass cytometry are important modern immunology tools for measuring expression levels of multiple proteins on single cells. The goal is to better understand the mechanisms of responses on a single cell basis by studying differential expression of proteins. Most current data analysis tools compare expressions across many computationally discovered cell types. Our goal is to focus on just one cell type. Our narrower field of application allows us to define a more specific statistical model with easier to control statistical guarantees.ResultsDifferential analysis of marker expressions can be difficult due to marker correlations and inter-subject heterogeneity, particularly for studies of human immunology. We address these challenges with two multiple regression strategies: a bootstrapped generalized linear model and a generalized linear mixed model. On simulated datasets, we compare the robustness towards marker correlations and heterogeneity of both strategies. For paired experiments, we find that both strategies maintain the target false discovery rate under medium correlations and that mixed models are statistically more powerful under the correct model specification. For unpaired experiments, our results indicate that much larger patient sample sizes are required to detect differences. We illustrate theRpackage and workflow for both strategies on a pregnancy dataset.ConclusionOur approach to finding differential proteins in flow and mass cytometry data reduces biases arising from marker correlations and safeguards against false discoveries induced by patient heterogeneity.
Comparative transcriptome analysis reveals ectopic delta-5 and delta-6 desaturases enhance protective gene expression upon Vibrio vulnificus challenge in Tilapia (Oreochromis niloticus)
Authors: Tu Pin-Yang , Huang Shin-Jie , Rajanbabu Venugopal , Wu Jen-Leih , Chen Jyh-Yih 
Published: March 2021

Abstract
Background
Tilapia (Oreochromis niloticus) cultures are frequently infected by Vibrio vulnificus, causing major economic losses to production units. Previously, tilapia expressing recombinant delta-5 desaturase and delta-6 desaturase (D56) were found to be resistant to V. vulnificus infection. In this report, we profile the D56-mediated molecular changes underlying this resistance in tilapia. A comparative transcriptome analysis was performed on V. vulnificus-infected wild-type and D56-transgenic tilapia using Illumina’s sequencing-by-synthesis approach. Gene enrichment analysis on differentially expressed unigenes was performed, and the expression patterns were validated by real-time PCR.

Results
Comparative transcriptome analysis was performed on RNA-sequence profiles obtained from wild-type and D56-transgenic tilapia at 0, 6 and 24 h post-infection with V. vulnificaus. GO and KEGG gene enrichment analyses showed that D56 regulates several pathways and genes, including fatty acid (FA) metabolism associated, and inflammatory and immune response. Expression of selected FA metabolism-associated, inflammatory and immune responsive genes was validated by qPCR. The inflammatory and immune responsive genes that are modulated by FA-associated D56 likely contribute to the enhanced resistance against V. vulnificus infection in Tilapia.

Conclusions
Transcriptome profiling and filtering for two-fold change variation showed that 3795 genes were upregulated and 1839 genes were downregulated in D56-transgenic tilapia. These genes were grouped into pathways, such as FA metabolism, FA elongation, FA biosynthesis, biosynthesis of unsaturated FA, FA degradation, inflammation, immune response, and chemokines. FA-associated genes and immune-related genes were modulated by D56 at 6 h and 24 h post infection with V. vulnificus. The expression patterns of FA-related genes, inflammatory genes, antimicrobial peptide genes and immune responsive genes at 0, 3, 6, 12, 24 and 48 h post-infection suggests these genes are involved in the enhanced resistance of D56 transgenic tilapia to V. vulnificus.
SCN11A gene deletion causes sensorineural hearing loss by impairing the ribbon synapses and auditory nerves
Authors: Zu Mian , Guo Wei-Wei , Cong Tao , Ji Fei , Zhang Shi-Li , Zhang Yue , Song Xin , Sun Wei , He David Z. Z. , Shi Wei-Guo , Yang Shi-Ming 
Published: March 2021

Abstract
Background
The SCN11A gene, encoded Nav1.9 TTX resistant sodium channels, is a main effector in peripheral inflammation related pain in nociceptive neurons. The role of SCN11A gene in the auditory system has not been well characterized. We therefore examined the expression of SCN11A in the murine cochlea, the morphological and physiological features of Nav1.9 knockout (KO) ICR mice.

Results
Nav1.9 expression was found in the primary afferent endings beneath the inner hair cells (IHCs). The relative quantitative expression of Nav1.9 mRNA in modiolus of wild-type (WT) mice remains unchanged from P0 to P60. The number of presynaptic CtBP2 puncta in Nav1.9 KO mice was significantly lower than WT. In addition, the number of SGNs in Nav1.9 KO mice was also less than WT in the basal turn, but not in the apical and middle turns. There was no lesion in the somas and stereocilia of hair cells in Nav1.9 KO mice. Furthermore, Nav1.9 KO mice showed higher and progressive elevated ABR threshold at 16 kHz, and a significant increase in CAP thresholds.

Conclusions
These data suggest a role of Nav1.9 in regulating the function of ribbon synapses and the auditory nerves. The impairment induced by Nav1.9 gene deletion mimics the characters of cochlear synaptopathy.
Physical disabilities caused by leprosy in 100 million cohort in Brazil
Authors: Sanchez Mauro Niskier , Nery Joilda Silva , Pescarini Júlia Moreira , Mendes André Alves , Ichihara Maria Yury , Teixeira Camila Silveira Silva , Penna Maria Lúcia Fernandes , Smeeth Liam , Rodrigues Laura Cunha , Barreto Maurício Lima , Brickley Elizabeth B. , Penna Gerson Oliveira 
Published: March 2021

Abstract
Background
Leprosy continues to be an important cause of physical disability in endemic countries such as Brazil. Knowledge of determinants of these events may lead to better control measures and targeted interventions to mitigate its impact on affected individuals. This study investigated such factors among the most vulnerable portion of the Brazilian population.

Methods
A large cohort was built from secondary data originated from a national registry of applicants to social benefit programs, covering the period 2001–2015, including over 114 million individuals. Data were linked to the leprosy notification system utilizing data from 2007 until 2014. Descriptive and bivariate analyses lead to a multivariate analysis using a multinomial logistic regression model with cluster-robust standard errors. Associations were reported as Odds Ratios with their respective 95% confidence intervals.

Results
Among the original cohort members 21,565 new leprosy cases were identified between 2007 and 2014. Most of the cases (63.1%) had grade zero disability. Grades 1 and 2 represented 21 and 6%, respectively. Factors associated with increasing odds of grades 1 and 2 disability were age over 15 years old (ORs 2.39 and 1.95, respectively), less schooling (with a clear dose response effect) and being a multibacillary patient (ORs 3.5 and 8.22). Protective factors for both grades were being female (ORs 0.81 and 0.61) and living in a high incidence municipality (ORs 0.85 and 0.67).

Conclusions
The findings suggest that the developing of physical disabilities remains a public health problem which increases the burden of leprosy, mainly for those with severe clinical features and worse socioeconomic conditions. Early diagnosis is paramount to decrease the incidence of leprosy-related disability and our study points to the need for strengthening control actions in non-endemic areas in Brazil, where cases may be missed when presented at early stages in disease. Both actions are needed, to benefit patients and to achieve the WHO goal in reducing physical disabilities among new cases of leprosy.
Influenza and other respiratory viral infections associated with absence from school among schoolchildren in Pittsburgh, Pennsylvania, USA: a cohort study
Authors: Read Jonathan M. , Zimmer Shanta , Vukotich Charles , Schweizer Mary Lou , Galloway David , Lingle Carrie , Yearwood Gaby , Calderone Patti , Noble Eva , Quadelacy Talia , Grantz Kyra , Rinaldo Charles , Gao Hongjiang , Rainey Jeanette , Uzicanin Amra , Cummings Derek A. T. 
Published: March 2021

Abstract
Background
Information on the etiology and age-specific burden of respiratory viral infections among school-aged children remains limited. Though school aged children are often recognized as driving the transmission of influenza as well as other respiratory viruses, little detailed information is available on the distribution of respiratory infections among children of different ages within this group. Factors other than age including gender and time spent in school may also be important in determining risk of infection but have been little studied in this age group.

Methods
We conducted a cohort study to determine the etiology of influenza like illness (ILI) among 2519 K–12 students during the 2012–13 influenza season. We obtained nasal swabs from students with ILI-related absences. Generalized linear mixed-effect regressions determined associations of outcomes, including ILI and laboratory-confirmed respiratory virus infection, with school grade and other covariates.

Results
Overall, 459 swabs were obtained from 552 ILI–related absences. Respiratory viruses were found in 292 (63.6%) samples. Influenza was found in 189 (41.2%) samples. With influenza B found in 134 (70.9%). Rates of influenza B were significantly higher in grades 1 (10.1, 95% CI 6.8–14.4%), 2 (9.7, 6.6–13.6%), 3 (9.3, 6.3–13.2%), and 4 (9.9, 6.8–13.8%) than in kindergarteners (3.2, 1.5–6.0%). After accounting for grade, sex and self-reported vaccination status, influenza B infection risk was lower among kindergarteners in half-day programs compared to kindergarteners in full-day programs (OR = 0.19; 95% CI 0.08–0.45).

Conclusions
ILI and influenza infection is concentrated in younger schoolchildren. Reduced infection by respiratory viruses is associated with a truncated school day for kindergarteners but this finding requires further investigation in other grades and populations.
Institutional outbreak involving multiple clades of IMP-producing Enterobacter cloacae complex sequence type 78 at a cancer center in Tokyo, Japan
Authors: Harada Sohei , Aoki Kotaro , Ohkushi Daisuke , Okamoto Koh , Takehana Kazumi , Akatsuchi Tomomi , Ida Keito , Shoji Daigo , Ishii Yoshikazu , Doi Yohei , Moriya Kyoji , Hayama Brian 
Published: March 2021

AbstractBackgroundInformation about the clinical and microbiological characteristics of IMP-producingEnterobacteraleshas been limited. Here, we describe an institutional outbreak of IMP-producingEnterobacter cloacaecomplex (ECC) involving multiple clades of ECC sequence type (ST) 78 strains.MethodsAntimicrobial susceptibility testing, whole-genome sequencing, and conjugation experiments of 18 IMP-producing ECC strains isolated during four-year study period were performed. Species and subspecies were determined by average nucleotide identity analysis and clonal relatedness of the isolates was analyzed with multilocus sequence typing and core-genome single nucleotide polymorphism (SNP) analysis. Relevant clinical information was extracted from medical records.ResultsFourteen of 18 IMP-producing ECC isolates were determined asEnterobacter hormaecheiST78. Sixteen isolates, including 13 isolates belonging to ST78, carriedblaIMP-1in In316-like class 1 integron and also carried IncHI2 plasmids. Conjugation experiments were successful for 12 isolates carryingblaIMP-1on IncHI2 plasmids and for an isolate carryingblaIMP-11on an IncL/M plasmid. Although isolation of ST78 strains was clustered in a 14-months period suggesting nosocomial transmission, these strains were subdivided into three clades by SNP analysis: clade A (n = 10), clade B (n = 1), clade C (n = 3). A part of clonal relatedness was unexpected by the epidemiological information at the time of isolation of the strains. Most of the IMP-producing ECC strains were susceptible to non-β-lactam antibiotics and had relatively low minimum inhibitory concentrations to carbapenems (≤4 μg/mL). Five of six infections caused by IMP-producing ECC were treated successfully.ConclusionsWhole-genome sequencing analysis revealed the outbreak was caused by three different clades of ST78 strains, where patients had favorable treatment outcome of the infections compared with that caused byEnterobacteralesproducing other carbapenemases, possibly due to their non-multidrug-resistant phenotype.
Feasibility and adherence to moderate intensity cardiovascular fitness training following stroke: a pilot randomized controlled trial
Authors: Reynolds Hanna , Steinfort Sarah , Tillyard Jane , Ellis Sarah , Hayes Alan , Hanson Erik D. , Wijeratne Tissa , Skinner Elizabeth H. 
Published: March 2021

Abstract
Background
Stroke is a leading cause of disability worldwide and the cardiovascular fitness levels of stroke survivors are diminished to an extent that impairs functioning and activities of daily living performance. While cardiovascular training seems an empirically appropriate intervention, the optimal dosage and intensity of cardiovascular training in stroke survivors remains unclear. The aim was to determine the safety and feasibility of moderate-intensity cardiovascular training following stroke, including measurement of adherence to training.

Methods
A pilot, prospective, patient- and assessor-blinded randomised controlled trial conducted in a tertiary, metropolitan hospital-based community rehabilitation centre. Eligibility criteria included ambulant (> 100 m), 6 weeks-12 months post stroke. Moderate-intensity fitness training or control (low-intensity) exercise was offered biweekly for 12 weeks. Outcome measures included adverse events, peak oxygen uptake (VO2), functional exercise capacity (6-Minute Walk Test, 10-m Walk Test) and health-related quality of life (Short Form-36) and mood (Patient Health Questionnaire, PHQ9).

Results
Feasibility: Seventy-one (50%) of 141 screened participants were eligible (29% did not agree to participate). Twenty participants (10 intervention, 10 control) were recruited. The median (%; IQR) supervised sessions was 19.5 (81%; 12, 20); and 20 (83%; 19, 22) in the intervention and control groups, respectively. Progression of duration and intensity was limited; mean of 10 sessions to achieve target duration (30 min). There were no adverse events. Baseline peak oxygen uptake (VO2) levels were low (15.94 ml/kg/min). Significant improvements in VO2 peak in both groups were observed (p < 0.05). Although there were no significant between-group differences, this feasibility trial was not powered to detect change.

Conclusions
Moderate-intensity fitness training was safe but achievement of target duration and intensity was challenging for stroke survivors. A definitive adequately-powered randomised trial is required. Alternative fitness training protocols may need to be explored.

Trial registration
The trial protocol was prospectively registered on the Australian New Zealand Clinical Trials Registry (ACTRN 12613000822785) on 25/07/2013.
Letter to the Editor in response to ‘Parental attachment and depressive symptoms in pregnancies complicated by twin-twin transfusion syndrome: a cohort study’
Authors: Rameh Georges , Tohme Pia , Abi-Habib Rudy , Chalouhi Gihad E 
Published: March 2021

AbstractTwin-twin transfusion syndrome is a highly morbid condition that can affect parental attachment and depression risk. Studies addressing this rare condition are hard to conduct and thus lacking in the literature. In this letter to the editor, we acknowledge the article of Mackie et al. entitled “Parental attachment and depressive symptoms in pregnancies complicated by twin-twin transfusion syndrome: a cohort study” to be of high importance and impact, but would like to discuss the extent of its conclusions, and push towards bigger studies in this field.
Ultrastructural study of closed macular hole- preliminary application of a novel high magnification module combining with OCT
Authors: Qiu Chang-Yu , Shi Yuan-Yuan , Zhao Hong-Wei , Nie Chuang , Dong Ming-Xia , Zhang Huai-Qiang , Zhao Jun , Xu Qian-Qian , Song Fei-Long , Guo Xiao-Hua , Shi Lin , Liu Chang-Ying , Gong Yu-Bo , Luo Ling 
Published: March 2021

Abstract
Background
As a novel high magnification module (HMM) combining with OCT (OCT-HMM) is able to detect the microstructure of retina, we apply it to explore the ultrastructure of the macula after closure of the idiopathic macular hole (IMH) by surgery.

Methods
This is an observational case series study in which patients with full-thickness IMHs who had undergone successful macular closure by vitrectomy and internal limiting membrane peeling and healthy subjects were recruited. After comprehensive ophthalmic examinations, the images of macular area were obtained and collected by professional operators using OCT-HMM. Then images were independently analyzed by 4 masked vitreoretinal specialists.

Results
A total of 24 IMH eyes and 42 healthy eyes were examined. HMM images were obtained in 10 IMH eyes. Among them, 4 eyes whose macula closed completely with recovery of photoreceptor layer presented a dark arc nasal to the fovea, oriented to the optic, and the notch of arc faced temporally. Six eyes in which the macula closed incompletely with photoreceptor cells loss revealed a dark ring with uneven bright spots inside. The other 14 eyes failed to obtain clear images by OCT-HMM. The contra lateral eyes of the patients and the healthy subjects’ eyes succeeded to obtain the HMM images which displayed evenly grey background thickly covered with tiny bright dots that was in similar size and evenly and widely distributed and there no dark arc or ring. OCT B-scan and IR images could be acquired in all of the IMH and healthy eyes.

Conclusion
The preliminary application of HMM has supplied us a brand-new insight into the microstructure of closed IMH. A dark arc sign could be detected with OCT-HMM in the macula which was functionally closed after surgery that was probably the healing mark on a microstructure photoreceptors level. Its existence and shape indicated that the functional closure followed by a retinal displacement mainly horizontally from temporal side to nasal side but not symmetric centripetally.