bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genome-wide selection signatures detection in Shanghai Holstein cattle population identified genes related to adaption, health and reproduction traits
Authors: Liu Dengying , Chen Zhenliang , Zhao Wei , Guo Longyu , Sun Hao , Zhu Kai , Liu Guanglei , Shen Xiuping , Zhao Xiaoduo , Wang Qishan , Ma Peipei , Pan Yuchun 
Published: October 2021

Abstract
Background
Over several decades, a wide range of natural and artificial selection events in response to subtropical environments, intensive pasture and intensive feedlot systems have greatly changed the customary behaviour, appearance, and important economic traits of Shanghai Holstein cattle. In particular, the longevity of the Shanghai Holstein cattle population is generally short, approximately the 2nd to 3rd lactation. In this study, two complementary approaches, integrated haplotype score (iHS) and runs of homozygosity (ROH), were applied for the detection of selection signatures within the genome using genotyping by genome-reduced sequence data from 1092 cows.

Results
In total, 101 significant iHS genomic regions containing selection signatures encompassing a total of 256 candidate genes were detected. There were 27 significant |iHS| genomic regions with a mean |iHS| score > 2. The average number of ROH per individual was 42.15 ± 25.47, with an average size of 2.95 Mb. The length of 78 % of the detected ROH was within the range of 1–2 MB and 2–4 MB, and 99 % were shorter than 8 Mb. A total of 168 genes were detected in 18 ROH islands (top 1 %) across 16 autosomes, in which each SNP showed a percentage of occurrence > 30 %. There were 160 and 167 genes associated with the 52 candidate regions within health-related QTL intervals and 59 candidate regions within reproduction-related QTL intervals, respectively. Annotation of the regions harbouring clustered |iHS| signals and candidate regions for ROH revealed a panel of interesting candidate genes associated with adaptation and economic traits, such as IL22RA1, CALHM3, ITGA9, NDUFB3, RGS3, SOD2, SNRPA1, ST3GAL4, ALAD, EXOSC10, and MASP2. In a further step, a total of 1472 SNPs in 256 genes were matched with 352 cis-eQTLs in 21 tissues and 27 trans-eQTLs in 6 tissues. For SNPs located in candidate regions for ROH, a total of 108 cis-eQTLs in 13 tissues and 4 trans-eQTLs were found for 1092 SNPs. Eighty-one eGenes were significantly expressed in at least one tissue relevant to a trait (P value < 0.05) and matched the 256 genes detected by iHS. For the 168 significant genes detected by ROH, 47 gene-tissue pairs were significantly associated with at least one of the 37 traits.

Conclusions
We provide a comprehensive overview of selection signatures in Shanghai Holstein cattle genomes by combining iHS and ROH. Our study provides a list of genes associated with immunity, reproduction and adaptation. For functional annotation, the cGTEx resource was used to interpret SNP-trait associations. The results may facilitate the identification of genes relevant to important economic traits and can help us better understand the biological processes and mechanisms affected by strong ongoing natural or artificial selection in livestock populations.
Soluble programmed death molecule 1 (sPD-1) as a predictor of interstitial lung disease in rheumatoid arthritis
Authors: Xu Li , Jiang Lichun , Nie Liuyan , Zhang Songzhao , Liu Lei , Du Yan , Xue Jing 
Published: October 2021

Abstract
Background
Previous studies have indicated that the programmed death molecule 1 (PD-1) signaling pathway may play a key role in rheumatoid arthritis (RA). However, the pathogenesis of rheumatoid arthritis-related interstitial lung disease (RA-ILD) is not clear. We examined the serum levels of soluble PD-1 in patients with RA and its relationship with RA-ILD.

Methods
Blood samples were obtained from 87 patients with RA (58 with ILD and 29 without ILD) and 45 healthy controls. Serum sPD-1 was measured by Enzyme-Linked Immunosorbent Assay. The pulmonary interstitial disease score was completed by a pulmonary physician and a radiologist through chest high-resolution computed tomography. Patients with RA-ILD were tested for lung function [e.g., forced vital capacity (FVC%), diffusing capacity of lungs for carbon monoxide (DLCO%)]. Associations between ILD and various markers, including sPD-1 and confounding factors, were investigated by logistic regression analysis. Diagnostic values of sPD-1 for the presence of ILD were investigated using receiver operating characteristic curve analysis.

Results
Serum sPD-1 levels were higher in RA patients with ILD than in RA patients without ILD and healthy controls (185.1 ± 109.0 pg/ml vs. 119.1 ± 77.5 pg/ml vs. 52.1 ± 21.7 pg/ml, P < 0.05). Serum sPD-1 levels were positively correlated with RF titer (P = 0.02, r = 0.249), anti-cyclic citrullinated peptide antibody status (P = 0.02, r = 0.243), and serum IgG levels (P < 0.001, r = 0.368), negatively associated with FVC% (P = 0.02, r = − 0.344), forced expiratory volume (FEV1%) (P  = 0.01, r = − 0.354), total lung capacity (TLC%) (P = 0.046, r = − 0.302), and was independently associated with the presence of ILD in RA patients by multivariate logistic regression analysis. The sensitivity and specificity of sPD-1 levels for the detection of ILD in RA patients were 58.6% and 75.9%, respectively. The area under the curve was 0.689.

Conclusion
Serum sPD-1 levels were increased in RA patients with ILD. Increased sPD-1 may be a valuable biomarker to predict the presence of ILD in patients with RA.
Longitudinal study: understanding the lived experience of couples across the trajectory of dementia
Authors: Mittelman Mary S. , O’Connor Maureen K. , Donley Tiffany , Epstein-Smith Cynthia , Nguyen Andrew , Nicholson Roscoe , Salant Rebecca , Shirk Steven D. , Stevenson Elizabeth 
Published: October 2021

AbstractBackgroundThe longitudinal study, “Couples Lived Experiences,” focuses on whether and how relationship characteristics of older couples change with the cognitive decline of one member of the couple, and how these changes affect each individual’s emotional and physical health outcomes. Until now, most psychosocial research in dementia has focused either on the person with dementia (PWD) or the caregiver separately. The previous literature examining relationship characteristics and their role in outcomes for the caregiver and PWD is scant and suffers from methodological issues that limit the understanding of which relationship characteristics most influence outcomes for caregivers and care-receivers and what other factors may mitigate or exacerbate their effects.MethodsWe will enroll 300 dyads and collect information via online interviews of each member of the couple, every 6 months for 3 years. Relationship characteristics will be measured with a set of short, well-validated, and reliable self-report measures, plus the newly developed “Partnership Approach Questionnaire.” Outcomes include global quality of life, subjective physical health, mental health (depression and anxiety), and status change (transitions in levels of care; i.e., placement in a nursing home). Longitudinal data will be used to investigate how relationship characteristics are affected by cognitive, functional, and behavioral changes, and the impact of these changes on health outcomes. Qualitative data will also be collected to enrich the interpretation of results of quantitative analyses.DiscussionPsychosocial interventions have demonstrated effectiveness in promoting the wellbeing of PWD and their caregivers. The knowledge gained from this study can lead to the development or enhancement of targeted interventions for older couples that consider the impact of cognitive and functional decline on the relationship between members of a couple and thereby improve their wellbeing.Trial registrationThis study has been registered with ClinicalTrials.gov. ClinicalTrials.gov Identifier is:NCT04863495.
Temporal changes in cardiovascular disease and infections in dialysis across a 22-year period: a nationwide study
Authors: Kaur Kamal Preet , Chaudry Mavish Safdar , Fosbøl Emil Loldrup , Østergaard Lauge , Torp-Pedersen Christian , Bruun Niels Eske 
Published: October 2021

Abstract
Background
Cardiovascular diseases (CVD) and infections are recognized as serious complications in patients with end stage kidney disease. However, little is known about the change over time in incidence of these complications. This study aimed to investigate temporal changes in CVD and infective diseases across more than two decades in chronic dialysis patients.

Methods
All patients that initiated peritoneal dialysis (PD) or hemodialysis (HD) between 1996 and 2017 were identified and followed until outcome (CVD, pneumonia, infective endocarditis (IE) or sepsis), recovery of kidney function, end of dialysis treatment, death or end of study (December 31st, 2017). The calendar time was divided into 5 periods with period 1 (1996–2000) being the reference period. Adjusted rate ratios were assessed using Poisson regression.

Results
In 4285 patients with PD (63.7% males) the median age increased across the calendar periods from 65 [57–73] in 1996–2000 to 69 [55–76] in 2014–2017, (p <  0.0001). In 9952 patients with HD (69.2% males), the overall median age was 71 [61–78] without any changes over time.
Among PD, an overall non-significant decreasing trend in rate ratios (RR) of CVD was found, (p = 0,071). RR of pneumonia increased significantly throughout the calendar with an almost two-fold increase of the RR in 2014–2017 (RR 1.71; 95% CI 1.46–2.0), (p <  0.001), as compared to the reference period. The RR of IE decreased significantly until 2009 (RR 0.43; 95% CI 0.21–0.87), followed by a return to the reference level in 2010–2013 (RR 0.87; 95% CI 0.47–1.60 and 2014–2017 (RR 1.1; 95% CI 0.59–2.04). A highly significant (p <  0.001) increase in sepsis was revealed across the calendar periods with an almost 5-fold increase in 2014–2017 (RR 4.69 95% CI 3.69–5.96).
In HD, the RR of CVD decreased significantly (p <  0.001) from 2006 to 2017 (RR 0.85; 95% CI 0.79–0.92). Compared to the reference period, the RR for pneumonia was high during all calendar periods (p <  0.05). The RR of IE was initially unchanged (p = 0.4) but increased in 2010–2013 (RR 2.02; 95% CI 1.43–2.85) and 2014–2017 (RR 3.39; 95% CI 2.42–4.75). No significant changes in sepsis were seen.

Conclusion
Across the two last decades the RR of CVD has shown a decreasing trend in HD and PD patients, while RR of pneumonia increased significantly, both in PD and in HD. Temporal trends of IE in HD, and particularly of sepsis in PD were upwards across the last decades.
Test-retest reliability of physical activity questionnaires in Parkinson’s disease
Authors: Ånfors Samuel , Kammerlind Ann-Sofi , Nilsson Maria H. 
Published: October 2021

AbstractBackgroundPeople with Parkinson’s disease are less physically active than controls. It is important to promote physical activity, which can be assessed using different methods. Subjective measures include physical activity questionnaires, which are easy and cheap to administer in clinical practice. Knowledge of the psychometric properties of physical activity questionnaires for people with Parkinson’s disease is limited. The aim of this study was to evaluate the test-retest reliability of physical activity questionnaires in individuals with Parkinson’s disease without cognitive impairment.MethodsForty-nine individuals with Parkinson’s disease without cognitive impairment participated in a test-retest reliability study. At two outpatient visits 8 days apart, the participants completed comprehensive questionnaires and single-item questions: International Physical Activity Questionnaire-Short Form (IPAQ-SF), Physical Activity Scale for the Elderly (PASE), Saltin-Grimby Physical Activity Level Scale (SGPALS) and Health on Equal Terms (HOET). Test-retest reliability was evaluated using the intraclass correlation coefficient (ICC), standard error of measurement (SEM), limits of agreement, weighted kappa or the Svensson method.ResultsSeveral of the physical activity questionnaires had relatively low test-retest reliability, including the comprehensive questionnaires (IPAQ-SF and PASE). Total physical activity according to IPAQ-SF had an ICC value of 0.46 (95% confidence interval [CI], 0.21–0.66) and SEM was 2891 MET-min/week. The PASE total score had an ICC value of 0.66 (95% CI, 0.46–0.79), whereas the SEM was 30 points. The single-item scales of SGPALS-past six months (SGPALS-6 m) and HOET question 1 (HOET-q1) with longer time frames (6 or 12 months, respectively) showed better results. Weighted kappa values were 0.64 (95% CI, 0.45–0.83) for SGPALS-6 m and 0.60 (95% CI, 0.39–0.80) for HOET-q1, whereas the single-item questions with a shorter recall period had kappa values < 0.40.ConclusionsSingle-item questions with a longer time frame (6 or 12 months) for physical activity were shown to be more reliable than multi-item questionnaires such as the IPAQ-SF and PASE in individuals with Parkinson’s disease without cognitive impairments. There is a need to develop a core outcome set to measure physical activity in people with Parkinson’s disease, and there might be a need to develop new physical activity questionnaires.
Genetic and treatment profiles of patients with concurrent Epidermal Growth Factor Receptor (EGFR) and Anaplastic Lymphoma Kinase (ALK) mutations
Authors: Yang Xiaodan , Zhong Jia , Yu Zhuo , Zhuo Minglei , Zhang Min , Chen Rongrong , Xia Xuefeng , Zhao Jun 
Published: October 2021

Abstract
Background
EGFR and ALK alternations often contribute to human malignancies, including lung cancer. EGFR and ALK mutations are usually sensitive to EGFR-tyrosine kinase inhibitors (TKIs) and ALK-TKIs. Although generally mutually exclusive, these mutations do co-exist in rare cases. This study investigated the frequencies, clinical characteristics, therapeutic efficacies, and genetic profiles of lung cancer patients with EGFR and ALK co-mutations.

Methods
Patients with concurrent EGFR and ALK mutations were included in this study, which analyzed mutation profiles and treatment histories. SPSS20.0 were used for survival analysis.

Results
Among 271 ALK-positive (ALK-pos) and 2975 EGFR-positive (EGFR-pos) patients in our database, nine (2.6% of ALK-pos and 0.2% of EGFR-pos) patients had concurrent EGFR and ALK mutations (including three exon19 Indel + EML4-ALK, two exon19 Indel + STRN-ALK, two L858R + L1152R, one L858R + EML4-ALK, and one G719C + S768I + STRN-ALK). Eight patients had at least one type of EGFR-TKIs treatment. The median progression free survival (PFS) of these patients on first-generation EGFR-TKIs was 14.5 months (95% CI: 11 - NR). Of these eight patients, one who progressed on Gefitinib and subsequently on Osimertinib had a T790M + C797G. The other seven EGFR-TKIs resistance patients had no known resistance mutations. No patients had ALK mutations before treatment, so ALK mutations may have developed as resistance mechanisms during EGFR-TKIs therapies. EGFR-TKIs-treated patients with EGFR/ALK L1152R mutations generally had a shorter PFS than patients with other mutation combinations.

Conclusions
ALK and EGFR mutations coincide at a relatively low frequency in lung cancer patients. ALK mutations developed either synchronously or heterochronously with EGFR mutations. Two ALK mutations (L1152R and STRN-ALK) may co-exist with EGFR mutations at a higher frequency than others. Most EGFR/ALK co-alteration patients (other than the EGFR/ALK L1152R type) can benefit from first line EGFR-TKIs.
Cerebrospinal fluid cytokine levels are associated with macrophage infiltration into tumor tissues of glioma patients
Authors: Kemmerer Constanze L. , Schittenhelm Jens , Dubois Evelyn , Neumann Laura , Häsler Lisa M. , Lambert Marius , Renovanz Mirjam , Kaeser Stephan A. , Tabatabai Ghazaleh , Ziemann Ulf , Naumann Ulrike , Kowarik Markus C. 
Published: October 2021

AbstractBackgroundDiffuse gliomas are the most common malignant tumors of the central nervous system with poor treatment efficacy. Infiltration of immune cells into tumors during immunosurveillance is observed in multiple tumor entities and often associated with a favorable outcome. The aim of this study was to evaluate the infiltration of immune cells in gliomas and their association with cerebrospinal fluid (CSF) cytokine concentrations.MethodsWe applied immunohistochemistry in tumor tissue sections of 18 high-grade glioma (HGG) patients (4 anaplastic astrocytoma, IDH-wildtype WHO-III; 14 glioblastomas (GBM), IDH-wildtype WHO-IV) in order to assess and quantify leucocytes (CD45) and macrophages (CD68, CD163) within the tumor core, infiltration zone and perivascular spaces. In addition, we quantified the concentrations of 30 cytokines in the same patients’ CSF and in 14 non-inflammatory controls.ResultsWe observed a significantly higher percentage of CD68+macrophages (21–27%) in all examined tumor areas when compared to CD45+leucocytes (ca. 3–7%); CD163+cell infiltration was between 5 and 15%. Compared to the tumor core, significantly more macrophages and leucocytes were detectable within the perivascular area. The brain parenchyma showing a lower tumor cell density seems to be less infiltrated by macrophages. Interleukin (IL)-7 was significantly downregulated in CSF of GBM patients compared to controls. Additionally, CD68+macrophage infiltrates showed significant correlations with the expression of eotaxin, interferon-γ, IL-1β, IL-2, IL-10, IL-13, IL-16 and vascular endothelial growth factor.ConclusionsOur findings suggest that the infiltration of lymphocytes is generally low in HGG, and does not correlate with cytokine concentrations in the CSF. In contrast, macrophage infiltrates in HGG are associated with CSF cytokine changes that possibly shape the tumor microenvironment. Although results point towards an escape from immunosurveillance or even exploitation of immune cells by HGG, further studies are necessary to decipher the exact role of the immune system in these tumors.
A randomized phase III study of short-course radiotherapy combined with Temozolomide in elderly patients with newly diagnosed glioblastoma; Japan clinical oncology group study JCOG1910 (AgedGlio-PIII)
Authors: Arakawa Yoshiki , Sasaki Keita , Mineharu Yohei , Uto Megumi , Mizowaki Takashi , Mizusawa Junki , Sekino Yuta , Ono Tomohiro , Aoyama Hidefumi , Satomi Kaishi , Ichimura Koichi , Kinoshita Manabu , Ohno Makoto , Ito Yoshinori , Nishikawa Ryo , Fukuda Haruhiko , Nishimura Yasumasa , Narita Yoshitaka ,   Brain Tumor Study Group and Radiation Therapy Study Group of the Japan Clinical Oncology Group
Published: October 2021

Abstract
Background
The current standard treatment for elderly patients with newly diagnosed glioblastoma is surgery followed by short-course radiotherapy with temozolomide. In recent studies, 40 Gy in 15 fractions vs. 60 Gy in 30 fractions, 34 Gy in 10 fractions vs. 60 Gy in 30 fractions, and 40 Gy in 15 fractions vs. 25 Gy in 5 fractions have been reported as non-inferior. The addition of temozolomide increased the survival benefit of radiotherapy with 40 Gy in 15 fractions. However, the optimal regimen for radiotherapy plus concomitant temozolomide remains unresolved.

Methods
This multi-institutional randomized phase III trial was commenced to confirm the non-inferiority of radiotherapy comprising 25 Gy in 5 fractions with concomitant (150 mg/m2/day, 5 days) and adjuvant temozolomide over 40 Gy in 15 fractions with concomitant (75 mg/m2/day, every day from first to last day of radiation) and adjuvant temozolomide in terms of overall survival (OS) in elderly patients with newly diagnosed glioblastoma. A total of 270 patients will be accrued from 51 Japanese institutions in 4 years and follow-up will last 2 years. Patients 71 years of age or older, or 71–75 years old with resection of less than 90% of the contrast-enhanced region, will be registered and randomly assigned to each group with 1:1 allocation. The primary endpoint is OS, and the secondary endpoints are progression-free survival, frequency of adverse events, proportion of Karnofsky performance status preservation, and proportion of health-related quality of life preservation. The Japan Clinical Oncology Group Protocol Review Committee approved this study protocol in April 2020. Ethics approval was granted by the National Cancer Center Hospital Certified Review Board. Patient enrollment began in August 2020.

Discussion
If the primary endpoint is met, short-course radiotherapy comprising 25 Gy in 5 fractions with concomitant and adjuvant temozolomide will be a standard of care for elderly patients with newly diagnosed glioblastoma.

Trial registration
Registry number: jRCTs031200099.
Date of Registration: 27/Aug/2020. Date of First Participant Enrollment: 4/Sep/2020.
Adolescents’ physical activity and sedentary behaviour in Indonesia during the COVID-19 pandemic: a qualitative study of mothers’ perspectives
Authors: Andriyani Fitria Dwi , Biddle Stuart J. H. , De Cocker Katrien 
Published: October 2021

Abstract
Background
Socio-behavioural adaptations during the COVID-19 pandemic may have significantly affected adolescents’ lifestyle. This study aimed to explore possible reasons affecting changes in physical activity and sedentary behaviour in Indonesian adolescents during the pandemic based on mothers’ perspectives.

Methods
We recruited parents (n = 20) from the Yogyakarta region of Indonesia (July–August 2020) using purposive and snowball sampling. Individual interviews were audio-recorded, transcribed verbatim and anonymised. Data were imported into NVivo software for a reflexive thematic analysis.

Results
The interviews lasted between 38 and 113 min (M = 65 min). Participants’ age ranged between 36 and 54 years (M = 42.6 years). Participants’ children ranged in age from 12 to 15 years (M = 13.7 years, female: 9, male: 11). Themes related to changes in physical activity during the pandemic were 1) self-determination and enjoyment, 2) supports from others, and 3) physical activity facilities and equipment. Themes related to changes in sedentary behaviour during the pandemic included 1) educational demands, 2) psychological effects due to the pandemic, 3) devices and internet availability, 4) parental control, and 5) social facilitators.

Conclusions
During the pandemic, mothers perceived their children to be less active and using more screen-based devices, either for educational or recreational purposes, compared to before. The present themes might be useful when developing interventions and policies promoting physical activity and reducing sedentary behaviour in adolescents. Interventions could, for example, consider increasing parents’ and adolescents’ awareness on current activity guidelines, providing education on healthier recreational screen time, and involving parents, peers, and teachers. Increasing the accessibility of physical activity facilities and equipment, making use of adolescents’ favourite program and social media for interventions, and providing activities that are fun and enjoyable may also important.