bluuebunny/crossref_metadata_2025_split huggingface dataset:
GJB4andGJC3variants in non-syndromic hearing impairment in Ghana
Authors: Adadey Samuel M , Esoh Kevin K , Quaye Osbourne , Amedofu Geoffrey K , Awandare Gordon A , Wonkam Ambroise 
Published: June 2020

The contribution of GJB4 and GJC3 gene variants to hearing impairment in Africa has not yet been studied. Here, we investigated the contribution of these genes to autosomal recessive non-syndromic hearing impairment in Ghanaian children. Hearing-impaired children from 141 simplex and 59 multiplex families were enrolled from 11 schools for the deaf in Ghana. The coding regions of GJB4 and GJC3 were amplified, sequenced, and analyzed for the study participants previously found to be negative for GJB2 and GJB6 variants. Seven GJB4 and one GJC3 variants were identified. One out of the seven GJB4 variants was classified as likely pathogenic, while the others were either benign or synonymous. The likely pathogenic variant (p.Asn119Thr/rs190460237) was predicted to be likely associated with hearing impairment. We modeled the wild-type and mutant proteins of this variant (p.Asn119Thr) to evaluate the effect of the mutation on protein structure and ligand-binding properties. The mutant and not the wild type had the potential to bind N-Ethyl-5ʹ-Carboxamido Adenosine (DB03719) which was due to a slight structural change that was observed. No clinically relevant variant was identified in the GJC3 gene. We report for the first time a likely pathogenic GJB4 variant that may be associated with non-syndromic hearing impairment in Ghana; the finding will add to the body of evidence of the contribution of GJB4 to hearing impairment cases around the world.Impact statementAlthough connexins are known to be the major genetic factors associated with HI, only a few studies have investigated GJB4 and GJC3 variants among hearing-impaired patients. This study is the first to report GJB4 and GJC3 variants from an African HI cohort. We have demonstrated that GJB4 and GJC3 genes may not contribute significantly to HI in Ghana, hence these genes should not be considered for routine clinical screening in Ghana. However, it is important to study a larger population to determine the association of GJB4 and GJC3 variants with HI.
Single nucleotide polymorphisms in telomere length-related genes are associated with hepatocellular carcinoma risk in the Chinese Han population
Authors: Huang Peng , Li Rong , Shen Lin , He Weizhou , Chen Shuo , Dong Yu , Ma Jiancang , Chen Xi , Xu Meng 
Published: June 2020

Background: Single nucleotide polymorphisms (SNPs) in telomere-related genes are associated with a high risk of hepatocellular carcinoma (HCC). In this study, we investigated the SNPs of telomere length-related genes and their correlation with HCC risk in the Chinese Han population. Materials and methods: A total of 473 HCC patients and 564 healthy volunteers were recruited. Overall, 42 SNPs distributed in telomere-related genes were selected and identified. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. Results: We found rs6713088 (OR = 1.27, 95% CI = 1.07–1.52, p = 0.007), rs843711 (OR = 1.29, 95% CI = 1.09–1.54, p = 0.004) and rs843706 (OR = 1.30, 95% CI = 1.09–1.55, p = 0.003) in the ACYP2 gene, rs10936599 (OR = 1.21, 95% CI = 1.02–1.44, p = 0.032) in the TERC gene and rs7708392 (OR = 1.24, 95% CI = 1.00–1.52, p = 0.042) in the TNIP1 gene were associated with high HCC risk (OR > 1). In contrast, rs1682111 (OR = 0.77, 95% CI = 0.64–0.94, p = 0.008) in the ACYP2 gene, rs2320615 (OR = 0.79, 95% CI = 0.64–0.99, p = 0.038) in the NAF1 gene, rs10069690 (OR = 0.75, 95% CI = 0.59–0.96, p = 0.021) and rs2242652 (OR = 0.70, 95% CI = 0.55–0.90, p = 0.004) in the TERT gene were associated with low HCC risk (OR < 1). Based on genotype frequency distributions, rs6713088, rs843645, rs843711 and rs843706 located in the ACYP2 gene as well as rs10936599 in the TERC gene were associated with a high incidence of HCC ( p < 0.05). In addition, SNPs in these genes could form a linkage imbalance haplotype. Specifically, the haploid ‘GC’ formed by rs10069690 and rs2242652 within the TERT gene increased the risk of HCC ( p < 0.05). Conclusion: SNPs in ACYP2, TERC, TERT and other genes were correlated with HCC risk in the Chinese Han population. These data may provide new insights into early diagnosis and screening of HCC.
Continuous Glucose Monitoring Decreases Hypoglycemia Avoidance Behaviors, but Not Worry in Parents of Youth With New Onset Type 1 Diabetes
Authors: Youngkin Erin M. , Majidi Shideh , Noser Amy E. , Stanek Kelly R. , Clements Mark A. , Patton Susana R. 
Published: June 2020

Background: Existing research shows that hypoglycemia fear (HF) is common in parents of children with established type 1 diabetes (T1D). We examined parental HF in the T1D recent-onset period and evaluated whether continuous glucose monitoring (CGM) adoption relates to improved outcomes of parental HF. Methods: In TACKLE-T1D, a prospective study of five- to nine-year olds with recent-onset T1D, parents completed the Hypoglycemia Fear Survey-Parents (HFS-P) at baseline (T1) and 6 (T2) and 12 (T3) months post-baseline. The HFS-P measures worry about hypoglycemia (HFS-Worry score) as well as hypoglycemia avoidance behaviors (HFS-Behavior score). We recorded CGM start dates for youth during the same time period through medical record review. Results: Between T1 and T2, 31 youth (32.3%) initiated CGM therapy, and between T2 and T3, an additional 17 youth (17.7%) began using CGM, leaving 48 youth who never initiated CGM therapy (50%) in the recent-onset period. Parents reported moderate HFS-Worry scores at T1 (32.9 ± 11.9), which increased between T1 and T2 (37.6 ± 11.4, P < .001) and plateaued between T2 and T3 (37.7 ± 12.4, P = .89). In contrast, parental HFS-Behavior scores decreased between T1 (33.1 ± 5.8) and T2 (32.2 ± 6.0, P = .005) and plateaued between T2 and T3 (32.2 ± 6.0, P = .95). Baseline HFS-Behavior and Worry scores were associated with increased adoption of CGM between T1-T2 and T2-T3, respectively. Parents of children initiating CGM therapy between T1 and T2 showed the largest decrease in HFS-Behavior ( P = .03). Conclusions: Initiating CGM therapy within the first 12 months of T1D may help reduce parents’ use of hypoglycemia avoidance behaviors, but has little effect on parents’ hypoglycemia worry.
Stentless hypospadias repair: The way forward
Authors: Sandlas Gursev , Tiwari Charu , Bothra Jyoti , Jadhav Bhushan , Shah Hemanshi 
Published: June 2020

Background: Stentless repair of hypospadias has been previously described in the literature for distal penile hypospadias repair. This was a prospective non-randomized study with the aim of assessing the efficacy of stentless repair in our health-care system. Methods: A total of 104 patients managed prospectively for hypospadias over a 30-month period who met the inclusion criteria were included in the study and underwent a stentless modified tubularized incised plate (TIP) urethroplasty repair (with a slight modification described subsequently) by three surgeons and were followed up for a minimum period of six months. Results: The median age at surgery was eight months. The site of meatus was glanular in 20 patients, coronal in 36 patients, sub-coronal in 38 patients and mid-penile in 10 patients. The median operative time was 47 minutes (range 32–76 minutes). The median time to first micturition was 140 minutes (range 10–300 minutes). Voiding difficulty was encountered in two patients, requiring catheterization. Three patients had superficial surgical site infections which were conservatively managed. All patients were discharged on the second postoperative day, except for the three patients with surgical site infection. On follow-up, two patients had a fistula. Conclusion: Stentless repair of hypospadias is the future and the new standard of care and should be used in every case where a modified TIP repair is feasible. This decreases complications from urethral stenting and decreases the duration of hospital stay. Both patient and parents are comfortable with this procedure. Level of evidence Level 2.
IL-1B rs2853550 polymorphism contributes to esophageal cancer susceptibility in Chinese Han population of Northwest China
Authors: Zhao Ruimin , Chen Xin , Ren Wanli , Dai Hao , Li Huajing , Li Honghui , Jia Ai , Wu Yue , Han Peng , Shao Yuan 
Published: June 2020

Abstract
Background
Esophageal cancer (EC) is one of the most common human cancers, with a particularly aggressive behavior and increased incidence worldwide. The aim of this study was to assess the associations of single-nucleotide polymorphisms (SNPs) in IL-1B with the risk of EC in a northwest Chinese Han population.

Methods
In order to evaluate the correlations between IL-1B polymorphisms and EC risk, an Agena MassARRAY platform was used to determine the genotype of the candidate SNPs among 384 EC patients and 499 controls. The associations between IL-1B variants and EC risk were examined using logistic regression analysis with adjustment for gender and age. Haplotype construction and analysis were performed to detect the potential associations between haplotypes within IL-1B and EC susceptibility. Additionally, bioinformatics databases were used for gene expression analysis and SNP functional prediction.

Results
A significant relationship was found between IL-1B rs2853550 and an increased risk of EC in the allele model [odds ratio (OR) = 1.38, 95% confidence interval (95% CI): 1.01–1.89, p = 0.041), the codominant model (A/G, OR = 1.63, 95% CI: 1.10–2.42, p = 0.011), and the dominant model (OR = 1.49, 95% CI: 1.02–2.18, p = 0.041). Functional analysis revealed the potential effects of rs2853550, which further reinforced its influence on EC susceptibility. However, there were no statistically significant differences for other SNPs or haplotypes between EC cases and healthy controls. Expression analysis conducted with dataset indicated that the expression level of IL-1B was higher in EC cases than that in normal samples.

Conclusions
This study demonstrated that rs2853550 in IL-1B might increase EC susceptibility in the Chinese Han population of Northwest China.
Genetic Dissection and Functional Differentiation of ALKa and ALKb, Two Natural Alleles of the ALK/SSIIa Gene, Responding to Low Gelatinization Temperature in Rice
Authors: Chen Zhuanzhuan , Lu Yan , Feng Linhao , Hao Weizhuo , Li Chuang , Yang Yong , Fan Xiaolei , Li Qianfeng , Zhang Changquan , Liu Qiaoquan 
Published: June 2020

Abstract
Background
ALK is the key gene controlling rice gelatinization temperature (GT), which is closely associated with the eating and cooking quality (ECQ) in rice (Oryza sativa L.). To date, at least three ALK alleles are thought to be responsible for the diversity of GT among rice cultivars. The ALKc/SSIIai allele with high activity of the soluble starch synthase IIa (SSIIa) controls high GT, but the accurate functional difference between ALKa and ALKb alleles, both controlling low GT, is not clearly elucidated. Thus, we generated rice near-isogenic lines (NILs) by introducing different ALK alleles into the japonica cultivar Nipponbare (Nip) to clarify the discrepant effects of the two low-GT ALK alleles.

Results
The results showed that the function of two low-GT alleles (ALKa and ALKb) was different, and a much lower GT was observed in NIL(ALKb) rice grains compared with that of Nip(ALKa). Moreover, the starches of NIL(ALKb) grains had a higher degree of branching, higher setback, consistence and higher cool pasting viscosity than those of Nip(ALKa). The lower expression level of ALKb, compared with ALKa, resulted in depleted intermediate chains and increased short chains of amylopectin, thus affected the thermal and pasting properties of NILs’ grains. Also, the data revealed both low-GT alleles were mainly found in temperate japonica, but more ALKb was found in other subpopulations such as indica as compared to ALKa.

Conclusions
Overall, all the results suggested that the function between two low-GT alleles was different, and the distribution of ALKb was much wider than that of ALKa among the subpopulations of cultivated rice.
Analysis of QTL for Grain Size in a Rice Chromosome Segment Substitution Line Z1392 with Long Grains and Fine Mapping of qGL-6
Authors: Zhang Ting , Wang Shiming , Sun Shuangfei , Zhang Yi , Li Juan , You Jing , Su Tian , Chen Wenbo , Ling Yinghua , He Guanghua , Zhao Fangming 
Published: June 2020

Abstract
Background
Grain size affects not only rice yield but is also an important element in quality of appearance. However, the mechanism for inheritance of grain size is unclear.

Results
A rice chromosome segment substitution line Z1392, which harbors three substitution segments and produces grains of increased length, was identified. The three chromosome segments were located on chromosomes 1, 5, and 6, and the average length of the substitution segment was 3.17 Mb. Cytological analysis indicates that the predominant cause of increased grain length in Z1392 could be cell expansion in the glumes. Seven quantitative trait loci (QTLs) for grain size related traits were identified using the secondary F2 population produced by Nipponbare/Z1392. The inheritance of grain length in Z1392 was mainly controlled by two major QTLs, qGL-5 and qGL-6. qGL-6 was localized on a 1.26 Mb region on chromosome 6, and OsARF19 may be its candidate gene. Based on QTL mapping, three single-segment substitution lines (S1, S2, and S3) and two double-segment substitution lines (D1 and D2) were selected, and the mapping accuracy for qGL-5 and qGL-6 was further verified using three single-segment substitution lines. Analysis of QTL additive and epistatic effects revealed that the additive effect of alleles qGL-5 and qGL-6 from ‘Xihui 18’ was estimated to increase grain length of Z1392 by 0.22 and 0.15 mm, respectively. In addition, a positive epistatic interaction between qGL-5 and qGL-6 was detected, which indicates that the pyramiding of qGL-5 and qGL-6 for grain length produces a novel genotype with longer grains.

Conclusions
Inheritance of grain length in the triple-segment substitution line Z1392 is mainly controlled by two major QTLs, qGL-5 and qGL-6. qGL-6 was found to be located in a 1.26 Mb region on chromosome 6, and OsARF19 may be its candidate gene. A positive epistatic interaction between qGL-5 and qGL-6 results in longer grains. The present results can be used to facilitate cloning of the qGL-5 and qGL-6 genes and contribute to improvement of grain yield in rice.
Hemoglobin concentration; a pathway to frailty
Authors: Steinmeyer Zara , Delpierre Cyrille , Soriano Gaelle , Steinmeyer Armand , Ysebaert Loic , Balardy Laurent , Sourdet Sandrine 
Published: June 2020

Abstract
Background
Frailty and hemoglobin concentration, above what would be considered clinical anemia, are two common findings in older patients that lead to an increased risk of negative health outcomes. The objective of this study is to evaluate whether hemoglobin concentration is an independent predictor of frailty and investigate possible causal pathways with a focus on the relationship between inflammation or nutrition and hemoglobin concentration.

Methods
1829 community-dwelling participants aged 65 years or older who visited the Toulouse frailty day hospital during 2011 and 2016 were included in this analysis. Patients underwent a comprehensive geriatric assessment and had a blood sample taken.
A series of multivariate logistic regression models were performed after minimizing potential influence from age, gender, kidney function, inflammation, cognition, nutritional status and certain socio-economic factors.

Results
Hemoglobin concentration and frailty are significantly associated after minimizing potential influence from other covariates (p < 0.005). An increase in one point of hemoglobin concentration is associated with a 14% risk reduction of being frail (OR = 0.86, 95%IC = 0.79–0.94). There was no evidence of a significant causal relationship between inflammation and nutritional status in the relationship between hemoglobin concentration and frailty status (p > 0.005).

Conclusions
Hemoglobin concentration is strongly associated with frailty in older adults. These results can have potentially important implications for prevention policies targeting frailty by identifying potential patients with high risk of adverse outcomes and functional outcomes.
Safety and efficacy of glibenclamide combined with rtPA in acute cerebral ischemia with occlusion/stenosis of anterior circulation (SE-GRACE): study protocol for a randomized controlled trial
Authors: Huang Kaibin , Ji Zhong , Wu Yongming , Huang Yunqiang , Li Guangning , Zhou Saijun , Yang Zhi , Huang Wenguo , Yang Guoshuai , Weng Guohu , Chen Pingyan , Pan Suyue 
Published: June 2020

Abstract
Background
Thrombolysis with recombinant tissue plasminogen activator (rtPA) improves outcome for patients with acute ischemic stroke (AIS), but many of them still have substantial disability. Glibenclamide (US adopted name, glyburide), a long-acting sulfonylurea, shows promising result in treating AIS from both preclinical and clinical studies. This study investigates the safety and efficacy of glibenclamide combined with rtPA in treating AIS patients.

Methods
This is a prospective, randomized, double-blind, placebo-controlled, multicenter trial with an estimated sample size of 306 cases, starting in January 2018. Patients aged 18 to 74 years, presented with a symptomatic anterior circulation occlusion with a deficit on the NIHSS of 4 to 25 points and treated with intravenous rtPA within the first 4.5 h of their clinical onsets, are eligible for participation in this study. The target time from the onset of symptoms to receive the study drug is of 10 h. Subjects are randomized 1: 1 to receive glibenclamide or placebo with a loading dose of 1.25 mg, followed by 0.625 mg every 8 h for total 5 days. The primary efficacy endpoint is 90-day good outcome, measured as modified Rankin Scale of 0 to 2. Safety outcomes are all-cause 30-day mortality and early neurological deterioration, with a focus on cardiac- and glucose-related serious adverse events.

Discussion
This study will provide valuable information about the safety and efficacy of oral glibenclamide for AIS patients treated with rtPA. This would bring benefits to a large number of patients if the agent is proved to be effective.

Trial registration
The trial was registered on September 14th 2017 at www.clinicaltrials.gov having identifier NCT03284463. Registration was performed before recruitment was initiated.
Is higher psychotropic medication burden associated with involuntary treatment under the Mental Health Act? A four-year Australian cohort study
Authors: Wheeler Amanda J. , Hu Jie , Profitt Caitlin , McMillan Sara S. , Theodoros Theo 
Published: June 2020

Abstract
Background
Involuntary treatment for individuals who lack sufficient capacity to make informed decisions regarding treatment has been associated with increased rates of injectable antipsychotics, antipsychotic polytherapy, and/or high doses. However, little is known about non-antipsychotic psychotropic prescription, or psychotropic medication burden as a more encompassing approach for people treated involuntarily. The aim of this study was to examine the relationship between Mental Health Act (MHA) status and psychotropic polypharmacy and/or high-dose medication prescribing practices in an Australian inpatient mental health unit.

Methods
A retrospective cohort study of 800 adults discharged from a large metropolitan Queensland mental health unit was undertaken. Data was collected for 200 individuals, discharged on at least one psychotropic medicine, at four time periods; Cohort 1 (on or before 31st January 2014), Cohort 2 (2015), Cohort 3 (2016) and Cohort 4 (2017). The number of prescribed medicines and total daily doses were recorded and reviewed for alignment with current clinical guidelines. Participant demographics and clinical characteristics were compared by individual MHA status using chi-square test for categorical variables and analysis of variance for continuous variables. Associations between MHA status and prescribing practices (psychotropic polypharmacy and/or high-dose prescribing) were assessed using bivariate and multivariate binomial logistic regression models. Age, gender, birth country, year of admission, admissions in previous 12 months, primary diagnosis, ECT/clozapine treatment, and other psychotropic medications were adjusted as covariates.

Results
Regression analysis found that compared to their voluntary counterparts, individuals treated involuntarily were 2.7 times more likely to be prescribed an antipsychotic at discharge, 8.8 times more likely to be prescribed more than one antipsychotic at discharge and 1.65 times more likely to be prescribed high-dose antipsychotic treatment at discharge. The adjusted model also found that they were half as likely to be prescribed an antidepressant at discharge.

Conclusion
Implicit review of justifications for increased psychotropic medication burden (antipsychotic polypharmacy and high-doses) in those treated involuntarily is required to ensure clinical outcomes and overall quality of life are improved in this vulnerable group. Clearly documented medication histories, reconciliation at discharge and directions for medication management after discharge are necessary to ensure quality use of medicines.
Family-centeredness of childhood obesity interventions: psychometrics & outcomes of the family-centered care assessment tool
Authors: Simione Meg , Sharifi Mona , Gerber Monica W. , Marshall Richard , Avalon Earlene , Fiechtner Lauren , Horan Christine , Orav E. John , Skelton Joseph , Taveras Elsie M. 
Published: June 2020

AbstractBackgroundIncorporating family-centered care principles into childhood obesity interventions is integral for improved clinical decision making, better follow-through, and more effective communication that leads to better outcomes and greater satisfaction with services. The purpose of this study is to evaluate the psychometric properties of a modified version of the Family Centered-Care Assessment (mFCCA) tool and to assess the family-centeredness of two clinical-community childhood obesity interventions.MethodsConnect for Healthwas a randomized trial testing the comparative effectiveness of two interventions that enrolled 721 children, ages 2–12 years, with a body mass index (BMI) ≥ 85th percentile. The two arms were (1) enhanced primary care; and (2) enhanced primary carepluscontextually-tailored, health coaching. At the end of the one-year intervention, the mFCCA was administered. We used Rasch analyses to assess the tool’s psychometrics and examined differences between the groups using multiple linear regression.Results629 parents completed the mFCCA resulting in an 87% response rate. The mean (SD) age of children was 8.0 (3.0) years. The exploratory factor analysis with 24 items all loaded onto a single factor. The Rasch modeling demonstrated good reliability as evidenced by the person separation reliability coefficient (0.99), and strong validity as evidenced by the range of item difficulty and overall model fit. The mean (SD, range) mFCCA score was 4.14 (0.85, 1–5). Compared to parents of children in the enhanced primary care arm, those whose children were in the enhanced primary careplushealth coaching arm had higher mFCCA scores indicating greater perception of family-centeredness (β = 0.61 units [95% CI: 0.49, 0.73]).ConclusionsUsing the mFCCA which demonstrated good psychometric properties for the assessment of family-centered care among parents of children with obesity, we found that individualized health coaching is a family-centered approach to pediatric weight management.Trial registrationClinicaltrials.govNCT02124460.