bluuebunny/crossref_metadata_2025_split huggingface dataset:
Population-specific, recent positive directional selection suggests adaptation of human male reproductive genes to different environmental conditions
Authors: Schaschl Helmut , Wallner Bernard 
Published: February 2020

AbstractBackgroundRecent human transcriptomic analyses revealed a very large number of testis-enriched genes, many of which are involved in spermatogenesis. This comprehensive transcriptomic data lead us to the question whether positive selection was a decisive force influencing the evolution and variability of testis-enriched genes in humans. We used two methodological approaches to detect different levels of positive selection, namely episodic positive diversifying selection (i.e., past selection) in the human lineage within primate phylogeny, potentially driven by sperm competition, and recent positive directional selection in contemporary human populations, which would indicate adaptation to different environments.ResultsIn the human lineage (after correction for multiple testing) we found that only the geneTULP2, for which no functional data are yet available, is subject to episodic positive diversifying selection. Using less stringent statistical criteria (uncorrectedp-values), also the geneSPATA16, which has a pivotal role in male fertility and for which episodes of adaptive evolution have been suggested, also displays a putative signal of diversifying selection in the human branch. At the same time, we found evidence for recent positive directional selection acting on several human testis-enriched genes (MORC1,SLC9B1,ROPN1L,DMRT1,PLCZ1,RNF17,FAM71DandWBP2NL) that play important roles in human spermatogenesis and fertilization. Most of these genes are population-specifically under positive selection.ConclusionEpisodic diversifying selection, possibly driven by sperm competition, was not an important force driving the evolution of testis-enriched genes in the human lineage. Population-specific, recent positive directional selection suggests an adaptation of male reproductive genes to different environmental conditions. Positive selection acts on eQTLS and sQTLs, indicating selective effects on important gene regulatory functions. In particular, the transcriptional diversity regulated by sQTLs in testis-enriched genes may be important for spermatocytes to respond to environmental and physiological stress.
Molecular bases for drought tolerance in common vetch: designing new molecular breeding tools
Authors: De la Rosa Lucía , Zambrana Encarnación , Ramirez-Parra Elena 
Published: February 2020

Abstract
Background
Common vetch (Vicia sativa L.) is a forage grain legume of high protein content and high nitrogen fixation, relevant in sustainable agriculture systems. Drought is the main limiting factor of this crop yield. Genetic resources collections are essential to provide genetic variability for breeding. The analysis of drought associated parameters has allowed us to identify drought tolerant and sensitive ecotypes in a vetch core collection.

Results
To understand the mechanisms involved in drought response we analysed transcriptomic differences between tolerant and sensitive accessions. Polymorphic variants (SNPs and SSRs) in these differential expressed genes (DEGs) have also been analysed for the design of drought-associated markers. A total of 1332 transcripts were commonly deregulated in both genotypes under drought. To know the drought adaptive response, we also analysed DEGs between accessions. A total of 2646 transcripts are DEG between sensitive and tolerant ecotypes, in watered and drought conditions, including important genes involved in redox homeostasis, cell wall modifications and stress-response. The integration of this functional and genetic information will contribute to understand the molecular mechanisms of drought response and the adaptive mechanisms of drought tolerance in common vetch. The identification of polymorphic variants in these DEGs has also been screened for the design of drought-associated markers that could be used in future breeding program strategies.

Conclusions
Our studies shed light for the first time in common vetch about the genes and pathways associated with drought tolerance. In addition, we identify over 100 potential drought associated polymorphism, as SNPs or SSRs, which are differently present in drought and tolerant genotypes. The use of these molecular markers for trait prediction would enable the development of genomic tools for future engineering strategies by screening of germplasm crop collections for traits related with crop drought resilience, adaptability or yield in vetch.
Recurrent epileptic seizures following cardiac catheterization with iodixanol: a case report
Authors: Lei Pingping , He Weiping , Shi Quan , Sun Meiying , Sun Zhigang 
Published: February 2020

Abstract
Background
Contrast-induced encephalopathy (CIE) is a rare complication of cardiac catheterization; clinical manifestations include cortical blindness, seizures and focal neurological deficits. In general, recurrent epileptic seizures following cardiac catheterization with iodixanol occur more rarely than do other complications.

Case presentation
Here, we report a case of a 76-year-old male patient who experienced unstable angina for nearly 10 months and was admitted to our hospital. Repeat cardiac catheterization was performed using iodixanol. At approximately 20 h after the first cardiac catheterization, his upper limbs began to exhibit slight trembling; the patient was conscious and could not control these movements. A total of 6 episodes occurred before the second cardiac catheterization was performed, with each episode lasting approximately 2 s. These symptoms were not treated. At approximately 2 h after the second cardiac catheterization, the symptoms became more severe, and the frequency of the episodes increased significantly; the symptoms had fully subsided at 6 h after the second operation. An electroencephalogram (EEG) demonstrated diffuse slowing with epileptiform abnormalities. Paroxysmal spike-wave and slow wave discharges were observed in the bilateral areas, and the abnormalities were marked in the frontal areas. These observations led us to conclude that the patient was experiencing epileptic seizures. During 6 months of monthly clinical follow-up visits after discharge, no abnormalities of the nervous system were found by cardiologists or neurologists, and the patient’s EEG was normal. No antiepileptic drugs were administered throughout this process.

Conclusions
CIE, especially recurrent epileptic seizures, is a rare but often reversible complication of cardiac catheterization with iodixanol. Its symptoms can be mild and therefore are easily ignored by physicians. Early CIE detection may be achieved by EEG. Repeated exposure to contrast agents carries the risk of recurrent epileptic seizures.
Pattern of vitreo-retinal diseases at the national referral hospital in Bhutan: a retrospective, hospital-based study
Authors: Rai Bhim B. , Morley Michael G. , Bernstein Paul S. , Maddess Ted 
Published: February 2020

Abstract
Background
Knowing the pattern and presentation of the diseases is critical for management strategies. To inform eye-care policy we quantified the pattern of vitreo-retinal (VR) diseases presenting at the national referral hospital in Bhutan.

Methods
We reviewed all new patients over three years from the retinal clinic of the Jigme Dorji Wangchuck National Referral Hospital. Demographic data, presenting complaints and duration, treatment history, associated systemic diseases, diagnostic procedures performed, and final diagnoses were quantified. Comparisons of the expected and observed frequency of gender used Chi-squared tests. We applied a sampling with replacement based bootstrap analysis (10,000 cycles) to estimate the population means and the standard errors of the means and standard error of the 10th, 25th, 50th, 75th and 90th percentiles of the ages of the males and females within 20-year cohorts. We then applied t-tests employing the estimated means and standard errors. The 2913 subjects insured that the bootstrap estimates were statistically conservative.

Results
The 2913 new cases were aged 47.2 ± 21.8 years. 1544 (53.0%) were males. Housewives (953, 32.7%) and farmers (648, 22.2%) were the commonest occupations. Poor vision (41.9%), screening for diabetic and hypertensive retinopathy (13.1%), referral (9.7%), sudden vision loss (9.3%), and trauma (8.0%) were the commonest presenting symptoms. Coexistent diabetes and hypertension were the most common associated systemic diseases. Haematological tests (blood sugar, HbA1c and lipid profile, 31.8%), OCT (27.4%), refraction (9.9%), B-scan (8.7%), fundus photography (8.0%) were the most commonly performed diagnostic tests. Hypertensive retinopathy (18.9%) was the commonest VR disease, followed by refractive errors referred for retinal evaluation (16.7%), diabetic retinopathy with macular oedema (15.8%), and AMD (11.0%). Retinal detachment was more prevalent in females (83 vs. 41, p = 0.007). Rare vision-threatening diseases like seasonal hyper-acute pan-uveitis also presented.

Conclusions
The developing VR service in Bhutan is challenged by the spectrum of diseases, limited human resources (e.g. one retinal surgeon during the study), and accessibility to tertiary eye-care services, all amidst difficult terrain. Sustained effort and robust coordination among the eye-care professionals, government and non-governmental organisations are critical for optimising VR services, especially as rates of diseases such as diabetes and hypertension grow.
Association between alcohol consumption and osteoarthritis prevalence in Korea as assessed by the alcohol use disorders identification test (AUDIT): a cross-sectional study
Authors: Kang Ah. Hyun , Kim Me-riong , Shin Joon-Shik , Lee Jinho , Lee Yoon Jae , Park Yeoncheol , Nam Dongwoo , Kim Eun-Jung , Ha In-Hyuk 
Published: February 2020

Abstract
Background
Osteoarthritis (OA) holds significance as a highly prevalent disorder in elderly populations. Various studies have been conducted on the association between alcohol consumption and OA, but the results have often been conflicting. The aim of this study was to investigate the relationship between alcohol consumption and OA in a large-scale sample representative of the Korean population.

Methods
Among the 25,534 participants surveyed in the fifth Korean National Health and Nutrition Examination Survey (2010–2012), 7165 individuals aged ≥50 who responded to drinking-related items were analyzed. The Alcohol Use Disorders Identification Test (AUDIT) grade was calculated, and radiologic examination analysis included the Kellgren-Lawrence (KL) grade of the lumbar spine, hip, and knee joints. Logistic regression analysis was performed to evaluate the association between AUDIT grades and OA through estimation of odds ratios (ORs).

Results
In crude analyses, OA (KL grade ≥ 2) of the lumbar spine and knee was more prevalent towards Zone I, but following adjustment, knee OA prevalence significantly increased in Zone III and IV compared to Zone I (Zone III: OR 1.464, 95% confidence interval (CI) 1.027–2.088; Zone IV: OR 1.543, 95% CI 1.028–2.317, respectively). Meanwhile, adjusted hip and lumbar OA values showed positive associations towards Zone IV, but did not reach statistical significance. Additional analyses of the association between alcohol consumption and pain severity of knee OA patients were nonsignificant.

Conclusions
These results imply that radiological knee OA, rather than symptomatic knee OA, is associated with alcohol consumption.
EPI immunization coverage, timeliness and dropout rate among children in a West Cameroon health district: a cross sectional study
Authors: Ateudjieu Jérôme , Yakum Martin Ndinakie , Goura André Pascal , Tembei Ayok Maureen , Ingrid Douanla Koutio , Bita’a Landry Beyala , Kenfack Bruno , Amada Lapia , Tadzong Isaac , Bissek Anne Cecile 
Published: February 2020

Abstract
Background
Monitoring of the expanded program on immunization’s performance is not only limited to routine periodic reports but equally includes surveys. Based on unpublished national EPI surveillance data from the past 5 years in Cameroon, the Foumban health district has reported a high number of vaccine preventable disease suspected cases. Contradictory information on the immunization coverage in this district exists from both administrative data and published literature. As a result, the objective of this study was to estimate the immunization coverage and dropout rate in age group 12–23 months and timeliness in age group 0–59 months among children in Foumban Health District (Cameroon), in 2018.

Method
This was a descriptive cross-sectional study targeting randomly selected children aged 0–59 months from Foumban health district. Data were collected by trained and supervised surveyors using a pretested questionnaire to describe the immunization coverage, timeliness and dropout rate in eighty clusters of about thirty buildings selected by stratified random sampling in July 2018.

Results
In total, 80 clusters covering 2121 buildings were selected and all were reached (100%). A total of 1549 (81.2%) households accepted to participate in the survey and 1430 children aged 0–59 months including 294 (20.6%) aged 12–23 months were enrolled into the study. Of these 1430 children, 427 [29.9 (27.4–32.2)%] aged 0–59 months were vaccinated with evidence. In the age group 12–23 months, the immunization coverage with evidence of BCG, DPT-Hi + Hb 3 and measles/rubella were 28.6(23.4–33.9)%, 22.8 (18.1–27.6)% and 14.3 (10.3–18.1)% respectively. Within age group 0–59 months; the proportion of children who missed their vaccination appointments increased from 23.3 to 31.7% for the vaccine planned at birth (BCG) and last vaccine planned (Measles/Rubella) for the EPI program respectively. In age group 12–23 months; the specific (DPT-Hi + Hb1–3) and general (BCG-Measles/Rubella) dropout rates of vaccination with evidence were 14.1 and 50.0% respectively.

Conclusion
Documented immunization coverage, dropout rate and timeliness in Foumban Health district are lower than that targeted by the Cameroon EPI. Competent health authorities have to take necessary actions to ensure the implementation of national guidelines with regards to children access to immunization. Also, studies have to be conducted to identify determinants of low immunization coverage and delays in immunization schedules as well as high dropout rates.
The use of complementary and alternative medicine in a multi-ethnic Asian population: results from the 2016 Singapore Mental Health Study
Authors: Seet Vanessa , Abdin Edimansyah , Vaingankar Janhavi A. , Shahwan Shazana , Chang Sherilyn , Lee Bernard , Chong Siow Ann , Subramaniam Mythily 
Published: February 2020

AbstractBackgroundThis study seeks to investigate factors associated with using complementary and alternative medicine (CAM) for a mental illness among the three major ethnic groups (Chinese, Indians and Malays) in the general population of Singapore.MethodsData from the 2016 Singapore Mental Health Study was used; responses from the “Services” section of the Composite International Diagnostic Interview version 3.0 (CIDI 3.0) administered during face-to-face household interviews with participants were analyzed to establish prevalence of CAM use among Singaporeans. Additionally, sociodemographic variables of interest were selected for sub-group regression analyses to yield correlates of CAM use among the three ethnic groups.Results6.4% of Singaporeans used at least one form of CAM in the past 12 months for their mental illness. Malays reported using CAM the most, followed by Indians and Chinese. Sociodemographic variables such as education and employment were differently associated with CAM use among the ethnicities. Across all three ethnic groups, CAM users were more likely to report poorer mental health-related quality of life.ConclusionDespite the significant differences in CAM use among Chinese, Malays and Indians, those who had a mental illness were significantly more likely to use CAM regardless of ethnicity. This highlights the need for communication between CAM practitioners and conventional mental healthcare providers for early referral when appropriate which would lead to improved healthcare delivery and better clinical outcomes.
Till death do us part: the effect of marital status on health care utilization and costs at end-of-life. A register study on all colorectal cancer decedents in Norway between 2009 and 2013
Authors: Bjørnelv Gudrun Maria Waaler , Edwin Bjørn , Fretland Åsmund Avdem , Deb Partha , Aas Eline 
Published: February 2020

Abstract
Background
Economic analyses of end-of-life care often focus on single aspects of care in selected cohorts leading to limited knowledge on the total level of care required to patients at their end-of-life. We aim at describing the living situation and full range of health care provided to patients at their end-of-life, including how informal care affects formal health care provision, using the case of colorectal cancer.

Methods
All colorectal cancer decedents between 2009 and 2013 in Norway (n = 7695) were linked to six national registers. The registers included information on decedents’ living situation (days at home, in short- or long-term institution or in the hospital), their total health care utilization and costs in the secondary, primary and home- and community-based care setting. The effect of informal care was assessed through marital status (never married, currently married, or previously married) using regression analyses (negative binominal, two-part models and generalized linear models), controlling for age, gender, comorbidities, education, income, time since diagnosis and year of death.

Results
The average patient spent four months at home, while he or she spent 27 days in long-term institutions, 16 days in short-term institutions, and 21 days in the hospital. Of the total costs (~NOK 400,000), 58, 3 and 39% were from secondary carers (hospitals), primary carers (general practitioners and emergency rooms) and home- and community-based carers (home care and nursing homes), respectively. Compared to the never married, married patients spent 30 more days at home and utilized less home- and community-based care, but more health care services at the secondary and primary health care level. Their total healthcare costs were significantly lower (−NOK 65,621) than the never married. We found similar, but weaker, patterns for those who had been married previously.

Conclusion
End-of-life care is primarily provided in the secondary and home-and community-based care level, and informal caregivers have a substantial influence on formal end-of-life care provision. Excluding aspects of care such as home and community-based care or informal care in economic analyses of end-of-life care provides a biased picture of the total resources required, and might lead to inefficient resource allocations.
Enhancement of bleomycin production in Streptomyces verticillus through global metabolic regulation of N-acetylglucosamine and assisted metabolic profiling analysis
Authors: Chen Hong , Cui Jiaqi , Wang Pan , Wang Xin , Wen Jianping 
Published: February 2020

Abstract
Background
Bleomycin is a broad-spectrum glycopeptide antitumor antibiotic produced by Streptomyces verticillus. Clinically, the mixture of bleomycin A2 and bleomycin B2 is widely used in combination with other drugs for the treatment of various cancers. As a secondary metabolite, the biosynthesis of bleomycin is precisely controlled by the complex extra-/intracellular regulation mechanisms, it is imperative to investigate the global metabolic and regulatory system involved in bleomycin biosynthesis for increasing bleomycin production.

Results
N-acetylglucosamine (GlcNAc), the vital signaling molecule controlling the onset of development and antibiotic synthesis in Streptomyces, was found to increase the yields of bleomycins significantly in chemically defined medium. To mine the gene information relevant to GlcNAc metabolism, the DNA sequences of dasR-dasA-dasBCD-nagB and nagKA in S. verticillus were determined by chromosome walking. From the results of Real time fluorescence quantitative PCR (RT-qPCR) and electrophoretic mobility shift assays (EMSAs), the repression of the expression of nagB and nagKA by the global regulator DasR was released under induction with GlcNAc. The relief of blmT expression repression by BlmR was the main reason for increased bleomycin production. DasR, however, could not directly affect the expression of the pathway-specific repressor BlmR in the bleomycins gene cluster. With at the beginning of bleomycin synthesis, the supply of the specific precursor GDP-mannose played the key role in bleomycin production. Genetic engineering of the GDP-mannose synthesis pathway indicated that phosphomannose isomerase (ManA) and phosphomannomutase (ManB) were key enzymes for bleomycins synthesis. Here, the blmT, manA and manB co-expression strain OBlmT/ManAB was constructed. Based on GlcNAc regulation and assisted metabolic profiling analysis, the yields of bleomycin A2 and B2 were ultimately increased to 61.79 and 36.9 mg/L, respectively.

Conclusions
Under GlcNAc induction, the elevated production of bleomycins was mainly associated with the alleviation of the inhibition of BlmT, so blmT and specific precursor synthesis pathways were genetically engineered for bleomycins production improvement. Combination with subsequent metabolomics analysis not only effectively increased the bleomycin yield, but also extended the utilization of chitin-derived substrates in microbial-based antibiotic production.
Hsa_circ_0011385 accelerates the progression of thyroid cancer by targeting miR-361-3p
Authors: Xia Fada , Chen Yong , Jiang Bo , Bai Ning , Li Xinying 
Published: February 2020

Abstract
Background
Thyroid cancer is an endocrine malignancy that is growing in incidence worldwide. Despite progress in diagnostics and treatment of thyroid cancer, prognosis remains poor. Emerging research has shown that circular RNAs (circRNAs) have crucial regulatory roles in cancers. However, the possible functions and mechanisms of hsa_circ_0011385 remain undetermined.

Materials and methods
Expression levels of hsa_circ_0011385 and miR-361-3p were evaluated by qRT-PCR assay. The interaction between hsa_circ_0011385 and miR-361-3p was verified by dual-luciferase reporter assay. Effects of hsa_circ_0011385 or miR-361-3p on cell viability, proliferation, cell cycle, apoptosis, migration and invasion were confirmed by cell counting kit-8 (CCK-8), carboxyfluoresceinsuccinimidyl ester (CFSE), flow cytometry, and Transwell assays in vitro. The effect of hsa_circ_0011385 on thyroid cancer progression was also determined by in vivo tumor formation assay. Target genes of miR-361-3p were predicted by gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, and the expression of apoptosis- and metastasis-related proteins were assessed by Western blot assay.

Results
Hsa_circ_0011385 upregulated in thyroid cancer; hsa_circ_0011385 knockdown inhibited thyroid cancer cell proliferation, migration and invasion, and promoted cell cycle arrest and apoptosis. In addition, hsa_circ_0011385 could negatively regulate miR-361-3p by functioning as a sponge. Hsa_circ_0011385 promoted thyroid cancer cell proliferation, migration and invasion and suppressed cell cycle arrest and apoptosis by targeting miR-361-3p in vitro. We also found that hsa_circ_0011385 knockdown dramatically inhibited thyroid cancer growth in vivo. Furthermore, hsa_circ_0011385 regulated expression of apoptosis and metastasis-related proteins in thyroid cancer.

Conclusions
Hsa_circ_0011385facilitated thyroid cancer cell proliferation, invasion and migration, and inhibited thyroid cancer cell cycle arrest and apoptosis by targeting miR-361-3p, suggesting that the hsa_circ_0011385/miR-361-3p axis might be a promising therapeutic target for thyroid cancer.