bluuebunny/crossref_metadata_2025 huggingface dataset:
Disparities in utilization of sexual and reproductive health services among high school adolescents from youth friendly service implemented and non-implemented areas of Southern Ethiopia
Authors: Haile Bayu , Shegaze Mulugeta , Feleke Tesfaye , Glagn Mustefa , Andarge Eshetu
Published: September 2020

Background: In recent years, much effort was made to improve access to sexual and reproductive health services (SRH) to adolescents and youths in Ethiopia particularly through establishment of youth friendly service (YFS) corners as part of the existing health care facilities. The existing evidences focused on investigating the utilization of SRH services at YFS established areas alone. There is a dearth of evidence which compares the SRH service use between the YFS implemented and non-implemented areas so that evidences can be drawn to suggest on the successes of the expansion of youth friendly corners. Methods: A school-based comparative cross-sectional study was conducted by employing a multistage cluster sampling method. A pre-tested self-administered questionnaire was used to collect data and the collected data were entered in to Epi data version 4.4.1 software and then exported to SPSS version 20 for analysis. χ2 test was used to see a significant difference in SRH service utilization among adolescents from YFS implemented and non-implanted areas. The association between the SRH services utilization and the independent variables was examined using binary logistic regression. Finally, variables having p-value less than or equal to 0.05 in the multivariable logistic regression model were considered as statistically significant.Results: There were a significant difference in the rate of SRH service utilization between YFS implemented (33.8%) and YFS non- implemented (9.9%) areas (χ2=37.49, p<0.001). Higher educational status of mothers (AOR=2.588, 95 % CI: 1.220, 5.491), having open discussion with family (AOR=3.175, 95%CI: 1.624, 6.206), having good knowledge (AOR= 4.511, 95% CI: 2.458, 8.278) and having positive attitude (AOR= 5.084, 95% CI: 2.764, 9.352) were positively associated with SRH services utilization.Conclusion: Compared with high schools from YFS implemented areas, the SRH service utilization was significantly lower among students from high schools where health facilities did not implement YFS. There is a need for enhancing efforts to establish YFS corners by the stakeholders at different hierarchies at places where the centers were not established so that SRH service uptake would be improved. In addition, it is better to promote open discussion with adolescents at the family level, and emphasis should be given for women education in the broad sense. Furthermore, wide-range awareness creation strategies should be used to address poor knowledge and negative attitude.
Development and validation of Egyptian developmental screening chart for children from birth up to 30 months
Authors: Shafie Ali M. El , Omar Zein A.L. , Bashir Mai M. , mahmoud sorour fayez , Basma El-sayedamr M. , Hussein Ahmed E. , Mostafa Alaa M. , Bahbah Wael A.
Published: September 2020

Background: Detecting developmental delay in children is an ongoing world commitment, especially for those below three years. Early detection prevents the adverse outcomes in this critical period of age. To accurately assess the development of children; a culturally appropriate screening tool must be used. Egypt lacks such tool and multiple studies have shown that western tools are not suitable in other cultures.Objectives: To develop and validate an easy, rapid, culturally appropriate and applicable screening chart for early detection of developmental delay among Egyptian children from birth up to 30 months and develop a Z score chart for motor and mental development follow up based on our Egyptian screening chart.Methods: A cross sectional randomized study was carried out on 1503 Egyptian children of both genders aged from birth up to 30 months assumed to have normal development according to the inclusion and exclusion criteria. They were selected from vaccination centers and well-baby clinics. Developmental milestones from Baroda development screening test (BDST) were applied on them after items were translated and adapted to Egyptian culture. Egyptian children developmental milestones scores were analyzed and carefully prepared in tables and charts. 97% pass levels of developmental achievements represent the threshold below which children are considered delayed. A Z-score chart for motor and mental development follow up was designed by calculating each age group achievement. The developed Egyptian developmental screening chart (EDSC) was validated against Ages and Stages Questionnaires (ASQ-3) as a Reference Standard in another different sample of 337 children in different age groups.Results: The developed EDSC is represented in a chart format with two curves 50% and 97% pass level. Children considered delayed when the score below 97% pass level. Results revealed a statistically significant difference between EDSC and BDST at 50% and 97% pass levels. A Z-score chart for motor and mental development follows up was designed by calculating each age group achievement. EDSC sensitivity and specificity were calculated 84.38 (95% CI: 67.21% to 94.72%) and 98.36 (95% CI: 96.22% to 99.47%) respectively with an overall test accuracy 97.03 (95% CI 94.61% to 98.57%) (p=<.001).Conclusions: Extensive revision of the BDST was needed in order to create and validate a more culturally appropriate Egyptian screening chart. This is the first study to create and validate an Egyptian-specific screening tool, to be rapid and easy to use in Egypt for early detection of developmental delay and enabling early intervention practices. A z-score curve is reliable for follow up motor and mental development by calculating each age group achievement.
Association between social network characteristics and depressive symptoms in South Korean adults: The moderating roles of age diversity and age difference
Authors: Jeon Ye Jin , Jung Sun Wook , Heo Ji Eun , Youm Yoosik , Kim Hyeon Chang , Jung Sun Jae
Published: September 2020

Background: This study aimed to examine the association between size and intimacy of social networks and substantial depressive symptoms, and further, to assess the moderating roles of age diversity and age difference in these linkages, in the community-dwelling adult population in South Korea.Methods: A South Korean population of 2,363 in the Cardiovascular and Metabolic Disease Etiology Research Center cohort was utilized. Each participant’s social network characteristics were measured using the egocentric social network analysis tool. Substantial depressive symptoms were assessed using the Beck Depression Inventory-II (BDI-II). Multivariable logistic regression was used to compute odds ratios (ORs) for substantial depressive symptoms by different social network characteristics.Results: Mean perceived intimacy of social networks had an inverse association with substantial depressive symptoms; Overall, the size of social networks had a negative association with depressive symptoms. In women, age diversity and age difference had moderation effects on the association of network size and intimacy with substantial depressive symptoms. The association of network size and intimacy with substantial depressive symptoms was stronger than women’s average (OR=3.23; 95% CI=1.91-5.47) when social networks had a higher age diversity (OR=4.95; 2.32-10.51) and higher age differences (OR=5.38; 2.22-13.05).Limitations: Substantial Depressive symptoms were measured according to self-assessed levels of depressive symptoms during the previous two weeks, which do not necessarily indicate depressive disorder. Categorization of certain variables was made considering the distribution, but not with the actual critical known cut-off.Conclusions: We found that low social network size and intimacy were linearly associated with substantial depressive symptoms in women. Women whose networks are small-sized, less intimate, and with high age diversity and age difference, especially with older persons are more likely to have depressive symptoms in South Korean settings.Trial registration: KCT0001038, Clinical Research Information Service (CRIS)
Benchmarking the research track record and level of appointment of Australian medical laboratory science academics
Authors: Donkin Rebecca , Broome Kieran , Swanepoel Libby
Published: September 2020

Background Benchmarking across and within universities is a common tool to evaluate performance of a program and maintain accreditation requirements. While teaching remains a primary responsibility of many academics, academic research performance is a major contributor towards career advancement and standards in the medical laboratory science profession. While anecdotal evidence suggests academics are active contributors to the evidence base of the profession, there is a high variability in research output in relation to institution and level of appointment. The aim of the study was to benchmark the research track record of Australian medical laboratory science academics and provide insight into how research productivity informs the level of appointment of academics across their career pathway.Methods A bibliographic analysis of Australian medical laboratory science faculty websites and corresponding Scopus citation database profiles was conducted. A description of current research track record and relationships with holding a doctorate, academic appointment level, research and teaching interests, and institutional characteristics were explored. Quantitative data and frequencies were analysed using IBM SPSS version 26 to benchmark research track records by academic appointment level.Results There were 124 academics identified from thirteen universities who had a teaching and research position in an undergraduate medical laboratory science program in Australia. Academics at the level of lecturer or higher typically held a doctorate (89%). Holding a doctorate strongly influenced the number of publications. The top 20% of researchers authored around half of the overall publications. The majority of academics did not have alignment of their major research and teaching areas however, alignment had no influence on number of publications. There was, however, an inconsistent relationship between metropolitan or regional university location and the number of publications.Conclusion Data from this study provides academics with benchmarks for the research track record required at each level of appointment. When drawing conclusions on academic progression, promotion and tenure through research track record it would be mindful to assess each on a case by case basis. Institution (metropolitan versus regional) and research interest appears to influence publication number, h-index and citation scores.
Intensity of end-of-life health care and mortality after systemic anti-cancer treatment in patients with advanced lung cancer
Authors: Oselin Kersti , Pisarev Heti , Ilau Keit , Kiivet Raul-Allan
Published: September 2020

Background: We aimed to study the mortality and intensity of health care in patients with advanced lung cancer who received systemic anti-cancer treatment (SACT) compared with patients who were not eligible for SACT (no-SACT). Methods: A retrospective cohort of lung cancer patients, who were treated at the North Estonia Medical Centre from 2015–2017, was linked to population-based health care data from the Estonian Health Insurance Fund. We calculated 14- and 30-day mortality after SACT and used a composite measure of intensity of care, comprised from the following: emergency department visit, admission to hospital, admission to intensive care unit, receipt of radiotherapy or systemic treatment. Results: The median overall survival (OS) of patients who received at least one cycle of SACT (n = 489) was 9.1 months and in patients with no-SACT (n = 289) 1.3 months (hazard ratio [HR]=4.23, 95% CI=3.60-5.00). In the SACT group 6.7% and 14.7% of patients died within 14 days and 30 days after the last cycle, respectively. During the final 30 days of life, intensive EOL care was received by 69.9% of the SACT patients and 43.7% of the no-SACT patients (p < 0.001). Among SACT patients, sepsis, bacterial infection and/or neutropenia had a significant adverse effect on survival (HR=1.7, 95% CI=1.3-2.21, p < 0.001), whereas the use of the granulocyte colony stimulating growth factor reduced the risk of death (HR= 0.71, 95% CI=0.54-0.92, p = 0.011). Conclusions: Significant proportions of patients with advanced lung cancer continue to receive intensive care near death. Our results highlight that neutropenia and infectious complications are still the primary cause of early SACT-related death.
Integrated Genomic and Transcriptomic Analysis Revealed Mutation Patterns of De-differentiated Liposarcoma and Leiomyosarcoma
Authors: Liu Wenshuai , Tong Hanxing , Zhang Chenlu , Zhuang Rongyuan , Guo He , Chentao Lv , Yang Hua , Lin Qiaowei , Guo Xi , Wang Zhiming , Wang Yan , Shen Feng , Wang Shengzhou , Wang Guan , Liu Jun , Dai Chun , Lu Weiqi , Zhang Yong , Zhou Yuhong
Published: September 2020

Background Treating patients with advanced sarcomas is challenging due to great histologic diversity among its subtypes. Leiomyosarcoma (LMS) and de-differentiated liposarcoma (DDLPS) are two common and aggressive subtypes of soft tissue sarcoma (STS). They differ significantly in histology and clinical behaviors. However, the molecular driving force behind the difference is unclear.Methods We collected 20 LMS and 12 DDLPS samples and performed whole exome sequencing (WES) to obtain their somatic mutation profiles. We also performed RNA-Seq to analyze the transcriptomes of 8 each of the LMS and DDLPS samples and obtained information about differential gene expression, pathway enrichment, immune cell infiltration in tumor microenvironment, and chromosomal rearrangement including gene fusions. Selected gene fusion events from the RNA-seq prediction were checked by RT-PCR in tandem with Sanger sequencing.Results We detected loss of function mutation and deletion of tumor suppressors mostly in LMS, and oncogene amplification mostly in DDLPS. A focal amplification affecting chromosome 12q13–15 region which encodes MDM2, CDK4 and HMGA2 is notable in DDLPS. Mutations in TP53, ATRX, PTEN, and RB1 are identified in LMS but not DDLPS, while mutation of HERC2 is only identified in DDLPS but not LMS. RNA-seq revealed overexpression of MDM2, CDK4 and HMGA2 in DDLPS and down-regulation of TP53 and RB1 in LMS. It also detected more fusion events in DDLPS than LMS (4.5 vs. 1, p=0.0195), and the ones involving chromosome 12 in DDLPS stand out. RT-PCR and Sanger sequencing verified the majority of the fusion events in DDLPS but only one event in LMS selected to be tested. The tumor microenvironmental signatures are highly correlated with histologic types. DDLPS has more endothelial cells and fibroblasts content than LMS. Conclusions Our analysis revealed different recurrent genetic variations in LMS and DDLPS including simultaneous upregulation of gene expression and gene copy number amplification of MDM2 and CDK4. Up-regulation of tumor related genes is favored in DDLPS, while loss of suppressor function is favored in LMS. DDLPS harbors more frequent fusion events which can generate neoepitopes and potentially targeted by personalized immune treatment.
Association between five types of Tumor Necrosis Factor-α Gene Polymorphism and Hepatocellular Carcinoma Risk: A Meta-Analysis
Authors: Wungu Citrawati Dyah Kencono , Ariyanto Fis Citra , Prabowo Gwenny Ichsan , Soetjipto Soetjipto , Handajani Retno
Published: September 2020

Background: Research focusing on the relationship between five types of tumor necrosis factor-alpha (TNF-α) SNPs and the risk of hepatocellular carcinoma (HCC) were still controversial. Hereby, we performed a meta-analysis to determine the association between TNF-α promoter SNPs: -1031 T/C, -863 C/A, -857 C/T, -308 G/A, and -238 G/A with HCC risk. Methods: We interrogated articles from journal database: PubMed, Pro-Quest, EBSCO, Science Direct, and Springer to determine the relationship between five types of SNPs in TNF-α gene with HCC risk. RevMan 5.3 software was used for analysis in fixed/random effect models. Results: This meta-analysis included 23 potential articles from 2004-2018 with 3,237 HCC cases and 4,843 controls. We found that SNP -863 C/A were associated with a significantly increased HCC risk (A vs C, OR=1.31, 95% CI=1.03-1.67). Similar results were obtained in -857 C/T (TT/CT vs CC, OR=1.31, 95% CI=1.06-1.62), -308 G/A (AA vs GG, OR=3.14, 95% CI=2.06-4.79), and -238 G/A (AA vs GG, OR=3.87, 95% CI=1.32-11.34). While no associations were observed between SNP TNF-α -1031 T/C and HCC risk.Conclusions: The present meta-analysis showed that TNFα SNPs -863C/A, -857 C/T, -308 G/A, and -238 G/A were associated with the risk of HCC.
Current Status of Scientific Research Accomplishments of Senior Eight-year-program Medical Students in China: A Multicenter Cross-sectional Questionnaire-based Study
Authors: Wan Mengyao , Liu Shuang , Zhu Jiawei , Xiao Sulong , Yuan Lei , Lei Xiaokang , Lei Hao , Shi Xiaomeng , You Wen , Ruan Gechong , Li Ji , Qian Jiaming
Published: September 2020

Backgrounds: Among the distinct medical education systems in China, the eight-year program is an elite program dedicated to cultivating physician scientists. Although the research ability of senior students in eight-year medical programs is a pivotal quality, it remains unclear. This study aimed to clarify the current status and challenges of students’ research experience, abilities and outputs.Methods: A multicenter cross-sectional study was conducted in five medical schools in northern China. Electronic questionnaires were sent to 235 randomly chosen fifth-grade or sixth-grade 8-year-program medical students. A total of 211 responses were collected and analyzed using SPSS 22.0.Results: Only 13.3% of participants chose research as their future career goal. Students generally felt that conducting research was stressful and difficult. The greatest obstacle was a lack of time due to heavy workloads. The two major motivations for research were graduation and future employment (75.8%) and research interest (24.2%). More than half of the students (142, 67.3%) had research experience by the time of the survey, among whom 84 students already had research outputs. A higher proportion of students with outputs was motivated by the requirements for graduation or employment compared to students without outputs (71.4% vs. 55.2%, P = 0.046).Conclusions: Senior 8-year-program medical students in China generally had high pressure to conduct research and devoted their efforts to overcome these challenges. More guidance and novel encouragement to enhance students’ initiative and interest in research could be provided by medical schools and educators in the future.
Analysis of cranial type characteristics in term infants: A multi-center study
Authors: Wang Yang , Bin Hu , Jianping Chen , Wenzhi Shen , Chengju Wang , Qin Chang , Wenzao Li , Fuxiang Qu , Qiuming Pan , Yuping Zhang
Published: September 2020

Background: Positional head deformity (PHD) is defined as a change in the shape of an infant's skull due to an external force. In certain cases, it can lead to cosmetic deformities or even neurological issues due to its impact on the developing nervous system. Therefore, we conducted this study to investigate the incidence and characteristics of PHD in term infants in China and preliminarily establish a localized diagnostic reference standard. Methods: Overall, 4456 term infants from three medical institutions in Chongqing were and divided and analyzed according to their age. Cranial vault asymmetry (CVA) and cephalic index (CI) were calculated in all infants. The current international diagnostic criteria were used to understand PHD incidence and analyze the CVA and CI distribution. Results: According to the current international standards, the total detection rate of PHD in Chongqing’s term infants was 81.5%, with brachycephaly alone being the most frequent (39.4%), followed by brachycephaly with plagiocephaly (34.8%) and plagiocephaly alone (6.2%). The detection rates of dolichocephaly were low: alone, 0.9% and combined with plagiocephaly, 0.2%. According to age, plagiocephaly (44.5%) and brachycephaly (82.0%) were the most frequent in the 2-3-month group. The 75th/90th/97th and 3rd/10th/25th/75th/90th/97th percentiles of CVA and CIs were 0.4/0.7/1.0 and 76.4/78.8/82.3/91.1/94.6/99.2%, respectively. Conclusions: According to the current international standards, the PHD detection rate among term infants in Chongqing was high. Therefore, a new diagnostic standard for Chinese infants was proposed where CVA ≥0.4 cm indicates plagiocephaly, CI ≥91% indicates brachycephaly, and CI ≤82% indicates dolichocephaly.
An anti-CD6 monoclonal antibody (itolizumab) reduces circulating IL-6 in severe COVID-19 elderly patients
Authors: Saavedra Danay , Añé-Kourí Ana Laura , Sánchez Naivy , Filgueira Lázaro Manuel , Betancourt Julio , Herrera Carlos , Manso Leniel , Chavez Elibet , Caballero Armando , Hidalgo Carlos , Lorenzo Geydi , Cepeda Meylan , Valenzuela Carmen , Ramos Mayra , León Kalet , Mazorra Zaima , Crombet Tania
Published: September 2020

Background: Since the COVID-19 outbreak an unprecedented challenge for healthcare systems around the world has been placed. In Cuba, the first case of COVID-19 was reported on March 11. Elderly with multiple comorbidities have been the most risky population. Although most patients present a mild to moderate disease, some have developed severe symptoms. One of the possible mechanisms underlying rapid disease progression is a cytokine storm, in which interleukin (IL) -6 seems to be a major mediator. Itolizumab is a humanized recombinant anti-CD6 monoclonal antibody (MAb), with the ability of reducing serum interferon gamma (INF-γ), tumour necrosis factor alpha (TNFα) and IL-6. Based on these previous results in patients with psoriasis and rheumatoid arthritis, an expanded access clinical trial was approved by the Cuban regulatory agency for COVID-19 critically, severely and moderately ill patients. Results: We show here a short kinetic of IL-6 serum concentration in the first 24 COVID-19 patients treated with itolizumab. Most of patients were elderly with multiple comorbidities. We found that with one itolizumab dose, the circulating IL-6 decreased in critically and severely ill patients, whereas in moderately ill patients the values didn’t rise as compared to their low baseline levels. Conclusion: These findings suggest that itolizumab could be an attractive therapeutic option to decrease the negative outcome of the cytokine storm in COVID-19 patients. Trial registration: CECMED IIC RD-EC 179, RPCEC00000311. Registered 4 May 2020 - Retrospectively registered, http://rpcec.sld.cu/ensayos/RPCEC00000311-Sp or http://rpcec.sld.cu/trials/RPCEC00000311-En
Short-duration, submaximal intensity exercise stress combined with adenosine triphosphate decreases artifacts in myocardial perfusion single-photon emission computed tomography
Authors: Shinoda Yukinori , Tachibana Koichi , Minamisaka Tomoko , Fukuoka Hidetada , Inui Hirooki , Ueno Keisuke , Inoue Soki , Mine Kentaro , Ueda Kumpei , Hoshida Shiro
Published: September 2020

Background: Myocardial perfusion single-photon emission computed tomography (SPECT) imaging with stress is a useful examination for detecting coronary artery disease. Since the presence of artifacts is remaining challenges, we aimed to define the minimum intensity of low-grade exercise stress levels combined with drug stress to reduce undesired artifacts and their related factors.Methods: We divided patients with suspicious coronary artery disease into 4 groups as follows: group A, adenosine triphosphate (ATP) for 6 min; group A+25 W, ATP+25 W exercise for 6 min; group A+35 W, ATP+35 W exercise for 6 min; group A+45 W, ATP+45 W exercise for 6 min) and enrolled only those whose summed stress scores were <3. Undesired artifacts were evaluated on the basis of heart-to-liver activity (H/L) ratio and heart-to-10 pixels below the heart (H/below the H) ratio. Results: The logarithmic values of H/L and H/below the H ratios were significantly higher in groups A+35 W and A+45 W than in group A (p<0.05, each). In all the patients, the logarithmic values of H/L and H/below the H ratios positively correlated with the increment of rate pressure product (RPP, p=0.002 and p=0.005, respectively) after stress in the univariate analysis. The left ventricular end-diastolic volume (LVEDV) after stress (p=0.002) negatively correlated with the logarithmic value of H/below the H ratio, but not H/L ratio. Although the increment of RPP was independently associated with the logarithmic values of both H/L (p=0.001) and H/below the H ratios (p=0.005), LVEDV was also independently associated with the logarithmic value of H/below the H ratio (p<0.001) in multivariate regression analysis under adjusting with age and sex.Conclusion: ATP plus ≥35 W exercise stress for 6 min was useful for reducing undesired artifacts after stress in myocardial perfusion SPECT. LVEDV after stress in addition to the increment of RPP was independently associated with the H/below the H ratio, but not the H/L ratio.
Efficacy of robotic versus laparoscopic approach in spleen preserving distal pancreatectomy for benign or low-grade malignant pancreatic tumors: study protocol for a randomized controlled trial
Authors: TIAN Feng , Lu Jun , Liu Cheng-xi , Guo Jun-chao
Published: September 2020

BackgroundBased on previous meta-analyses and comparative evidence, robotic approach might lead to a higher or at least similar spleen-preservation rates when comparing with laparoscopic approach in spleen preserving distal pancreatectomy (SPDP) for benign or low-grade malignant pancreatic tumors1–3. But high-quality evidence lacks and controversy exists. Therefore, we planned to initiate a prospective, patient-blinded, randomized, controlled trial (RCT) to compare robotic assisted spleen preserving distal pancreatectomy (RSPDP) with laparoscopic spleen preserving distal pancreatectomy (LSPDP), with special consideration to the success rate of splenic vessel-preserving (Kimura) approach, as well as perioperative variables, and cost analysis.MethodsPatients with benign or low-grade malignant pancreatic tumors are potential candidates for this RCT. Enrolled participants are randomized into RSPDP (observational arm) or LSPDP (control arm) groups as a ratio of 1:1. The primary outcome is the success rate of splenic vessel-preserving (Kimura) approach. The secondary outcomes include total success rate of spleen preserving (Kimura and Warshaw approaches), intraoperative variables, time to functional recovery, postoperative complications, mortality, and cost/efficacy analysis.DiscussionWe plan to conduct a randomized controlled trial to detect the potential advantages of robotic approach in spleen vessels preservation compared with traditional laparoscopic approach. RSPDP may improve spleen vessels preservation rate in selected patients.Trial registrationChinese Clinical Trial Registry, No: ChiCTR2000029177. Registered on 18 January, 2020.
Clinical Characteristics and Prognostic Implications of BRCA-associated Tumors in Males: A Pan-tumor Survey
Authors: Sun Peng , Li Yue , Chao Xue , Li Jibin , Luo Rongzhen , Li Mei , He Jiehua
Published: September 2020

Background The BRCA mutation (BRCAm) in males has been reported to confer a higher risk for the development of various tumors. However, little is known about its clinicopathologic features and prognostic implications.Design We conducted a retrospective pan-tumor survey on 346 cases of BRCA-associated tumors in males. Comparative analyses were conducted among male and female patients with BRCAm (n=349), as well as in male patients without BRCAm (n=4577).Results Similar incidences of BRCAm (6.0 vs. 6.6%) and age at diagnosis of tumor (median, 65 vs. 60 years) were observed in male and female patients. Carcinomas of the lung, bladder, stomach, and cutaneous melanoma were the frequent tumors demonstrating BRCAm in males, of which the majority were stage II or III diseases with a higher frequency of BRCA2 mutations. Compared to that in the non-BRCAm group, cutaneous melanoma (16.3 vs. 5.0%), lung cancer (19.4 vs. 11.8%), bladder cancer (15.6 vs. 5.6%), and stomach cancer (11.9 vs. 5.5%) accounted for a higher proportion in the BRCAm group. Advanced disease and more mutation counts (median, 322 vs. 63 mutations) were also found in the BRCAm group. A total of 127 BRCA1 and 311 BRCA2 mutations were identified, of which 21.8% and 28.6% were deleterious, respectively. Frequent deleterious variants were identified in carcinomas of the breast (100.0%), colorectum (62.2%), prostate (43.3%), and stomach (42.9%). BRCA1 fusions with NF1, FAM134C, BECN1, or LSM12 and recurrent BRCA2 mutations at P606L/S, E832K/G, and T3033Lfs*29 were detected. Frameshift mutations in BRCA2 at N1784 (N1784Kfs*3, N1784Tfs*3) were frequently observed in both male and female patients. Compared with those in females, BRCA mutations in males were associated with decreased overall survival (OS) and progression-free survival (PFS). Male patients with deleterious BRCAm displayed increased OS compared with non-BRCAm carriers. The subgroup analysis demonstrated that BRCAm was associated with increased OS in gastric and bladder cancers, decreased PFS in prostate, esophageal, and head and neck cancers, and decreased OS in glioma/glioblastoma in males.Conclusion These findings provide an overview of the distinct characteristics and clinical outcomes of male patients with BRCA-associated tumors, suggesting the importance of further genetic BRCA testing in males.
Do Cognitive Performance and Physical Function Differ between Individuals with Motoric Cognitive Risk Syndrome and those with Mild Cognitive Impairment?
Authors: Cheng Fang-Yu , Chang Yuanmay , Cheng Shih-Jung , Shaw Jin-Siang , Lee Chuo-Yu , Chen Pei-Hao
Published: September 2020

BackgroundMotoric cognitive risk syndrome (MCR) is defined by slow gait speed combined with subjective cognitive complaint. MCR is a predementia syndrome, similar to mild cognitive impairment (MCI). However, there is currently no study comparing the differences in cognitive performance and physical function between these two types of cognitive impairment. Thus, the aim of this study is to compare cognitive performance and physical function in individuals with MCR versus MCI. MethodsA total of 77 participants, free of dementia, were recruited from the neurological outpatient clinic of a medical center in Taiwan. Participants were separated into two groups, MCR (n=33) and MCI (n=44) groups, based on definition criteria from previous studies. Cognitive performance, including executive function, attention, working memory, episode memory, visuospatial function, and language, were measured. Physical functions such as activities in daily living, the Tinetti Assessment Scale, and the Timed Up and Go test were also measured. ResultsExecutive function, attention, working memory, episodic memory and language were all significantly lower in the MCR group than the MCI group. Abilities related to physical function, including those measured by the Tinetti Assessment Scale and the Timed Up and Go test, were significantly lower in the MCR group than the MCI group. ConclusionsWe noted that cognitive performance and physical function were lower in MCR individuals than MCI but without MCR individuals. The significant differences between those two groups may provide insight that MCR might lead to more severe overall functional deterioration in older adults than MCI but without MCR patients.
Metabolomics analysis reveals Embden Meyerhof Parnas pathway activation and flavonoids accumulation during dormancy transition in tree peony
Authors: Zhang Tao , Yuan Yanchao , Zhan Yu , Cao Xinzhe , Liu Chunying , Zhang Yuxi , Gai Shupeng
Published: September 2020

Background: Bud dormancy is a sophisticated strategy which plants evolve to survive in tough environments. Endodormancy is a key obstacle for anti-season culture of tree peony, and sufficient chilling exposure is an effective method to promote dormancy release in perennial plants including tree peony. However, the mechanism of dormancy release is still poorly understood, and there are few systematic studies on the metabolomics during chilling induced dormancy transition.Results: The tree peony buds were treated with artificial chilling, and the metabolmics analysis was employed at five time points after 0-4ºC treatment for 0, 7, 14, 21 and 28 d, respectively. A total of 535 metabolites were obtained and devided into 11 groups including flavonoids, amino acid and its derivatives, lipids, organic acids and its derivates, nucleotide and its derivates, alkaloids, hydroxycinnamoyl derivatives, carbohydrates and alcohols, phytohormones, coumarins and vitamins. Totally, 118 differential metabolites (VIP≥1, P<0.05) during chilling treatment process were detected, and their KEGG pathways involved in several metabolic pathways related to dormancy. Sucrose was the most abundant carbohydrate in peony bud. Starch was degradation and Embden Meyerhof Parnas (EMP) activity were increased during the dormancy release process, according to the variations of sugar contents, related enzyme activities and key genes expression. Flavonoids synthesis and accumulation were also promoted by prolonged chilling. Moreover, the variations of phytohormones (salicylic acid, jasmonic acid, abscisic acid, and indole-3-acetic acid) indicated they played different roles in dormancy transition.Conclusion: Our study suggested that starch degradation, EMP activation, and flavonoids accumulation were crucial and associated with bud dormancy transition in tree peony.
Proposal and psychometric validation of the Severe Acute Respiratory Syndrome - Coronavirus-2 Fear Scale (SCoV-2-FS)
Authors: Almeida Sérgio Monteiro de , Villibor Clara Putini , Carstensen Suzana , Petterle Ricardo Rasmussen
Published: September 2020

Background: The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has created an unprecedented global health, economic, and social challenges, generating fear. Fear can cause a range of physical and psychological disorders including depression, anxiety, and panic. Leading to lower social isolation and adherence to security measures, consequently increasing infection risk. The objective was to validate an 11-item unidimensional fear scale to identify and assess the severity of the fear of SARS-CoV-2. Methods: This was a cross-sectional study conducted through an online survey questionnaire. The sample included the Brazilian general population, randomly recruited by social networking platforms, during the pandemic. Participants aged ≥18 were included. A self-applicable fear scale named as the SARS-CoV-2 Fear Scale (SCoV-2-FS), comprising 11 questions addressing the fear of SARS-CoV-2 infection in performing daily activities was validated. The reliability and validity of the SCoV-2-FS were psychometrically evaluated using reliability measures and confirmatory factor analysis (CFA). The sample comprised 1332 Brazilian participants. Results: Cronbach’s α was 0.9, indicating very good internal reliability. The results of the CFA showed that the unidimensional factor structure of the SCoV-2-FS fitted well with the data.Limitations: The sampling method could have introduced selection bias in terms of socio-demographics.Conclusion: The SCoV-2-FS is a valid and reliable tool with robust psychometric properties, useful for assessing the psychological impact of fear due to COVID-19. Clinical relevance: The development of a scale may assist in the development of measures to control mental health disorders resulting from fear during and after the pandemic.
Improved thermostability of creatinase from Alcaligenes Faecalis through non-biased phylogenetic consensus-guided mutagenesis
Authors: Bai Xue , Li Daixi , Ma Fuqiang , Deng Xi , Luo Manjie , Feng Yan , Yang Guangyu
Published: September 2020

Background: Enzymatic quantification of creatinine has become an essential method for clinical evaluation of renal function. Although creatinase (CR) is frequently used for this purpose, its poor thermostability severely limits industrial applications. Herein, we report a novel creatinase from Alcaligenes faecalis (afCR) with higher catalytic activity and lower KM value, than currently used creatinases. Furthermore, we developed a non-biased phylogenetic consensus method to improve the thermostability of afCR. Results: We applied a non-biased phylogenetic consensus method to identify 59 candidate consensus residues from 24 creatinase family homologs for screening afCR mutants with improved thermostability. Twenty-one amino acids of afCR were selected to mutagenesis and 11 of them exhibited improved thermostability compared to the parent enzyme (afCR-M0). Combination of single-site mutations in sequential screens resulted in a quadruple mutant D17V/T199S/L6P/T251C (M4-2) which showed ~1700-fold enhanced half-life at 57 ºC and a 4.2 ºC higher T5015 than that of afCR-M0. The mutant retained catalytic activity equivalent to afCR-M0, and thus showed strong promise for application in creatinine detection. Structural homology modeling revealed a wide range of potential molecular interactions associated with individual mutations that contributed to improving afCR thermostability. Conclusions: Results of this study clearly demonstrated that the non-biased-phylogenetic consensus design for improvement of thermostability in afCR is effective and promising in improving the thermostability of more enzymes.
Molecular Remission at T cell level in Patients with Rheumatoid Arthritis
Authors: Inamo Jun , Suzuki Katsuya , Takeshita Masaru , Kondo Yasushi , Okuzono Yuumi , Koga Keiko , Kassai Yoshiaki , Takiguchi Maiko , Kurisu Rina , Morita Rimpei , Yoshimura Akihiko , Takeuchi Tsutomu
Published: September 2020

Background. While numerous disease-modifying anti-rheumatic drugs (DMARDs) has brought about a dramatic paradigm shift in the management of rheumatoid arthritis (RA), unmet needs remain such as small proportion of achievement drug-free patients. The aim of this study is to explore key molecules for remission at T cell level, which is known to involve the pathogenesis of RA deeply, and investigate disease course of patients who achieved molecular remission (MR).Methods. We enrolled a total of 46 patients with RA and 10 healthy controls (HCs). We performed gene expression profiling and selected remission signature genes in CD4+ T cells and CD8+ T cells of patients with RA using machine learning methods. In addition, we investigated the benefit of achieving MR on disease control thereafter.Results. We identified 9 and 23 genes that were associated with clinical remission in CD4+ and CD8+ T cells. Principal component analysis (PCA) demonstrated expression profiling of them was similar with HCs. As to remission signature genes in CD4+ T cells, PCA result was reproduced using validation cohort, indicating their robustness. There was a trend towards better disease control during 12 months follow-up in patients treated with tocilizumab in deep MR than those in non-deep MR, although it was not significant.Conclusion. We identified robust genes which represented remission status in CD4+ T cells using machine learning techniques. The current study will promote our understandings about molecular mechanism to achieve deep remission in the management of RA.Trial registration: Not required.
Systemic Lupus Erythematosus Activity and Hydroxychloroquine Use Before and After End-Stage Renal Disease
Authors: Guerrero Maria Salgado , Jimenez Alejandra Londono , Dobrowolski Chrisanna , Mowrey Wenzhu B. , Goilav Beatrice , Wang Shudan , Broder Anna
Published: September 2020

Background: SLE manifestations after ESRD may be underdiagnosed and undertreated, contributing to increased morbidity and mortality. Whether specific symptoms persist after ESRD or a shift towards new manifestations occurs has not been extensively studied, especially in the non-Caucasian patients in the United States. In addition, hydroxychloroquine (HCQ) prescribing patterns post-ESRD have not been described. The objective of this study was to assess lupus activity and HCQ prescribing before and after ESRD development. Knowledge gained from this study may aid in the identification of SLE manifestations and improve medication management post-ESRD. Methods: We performed a retrospective cohort study of SLE patients with incident ESRD between 2010 and 2017. SLE-related symptoms, serologic markers of disease activity, and medication use were collected from medical records before and after ESRD development.Results: Fifty-nine patients were included in the study. Twenty-five (43%) patients had at least one clinical (non-renal) SLE manifestation documented within 12 months before ESRD. Of them, 11/25 (44%) continued to experience lupus symptoms post-ESRD; 9 patients without clinical or serological activity pre-ESRD developed new symptoms of active SLE. At the last documented visit post-ESRD, 42/59 (71%) patients had one or more clinical or serological markers of lupus activity; only 17/59 (29%) patients achieved clinical and serological remission.Thirty-three of 59 (56%) patients had an active HCQ prescription at the time of ESRD. Twenty-six of the 42 (62%) patients with active SLE manifestations post-ESRD were on HCQ. Patients who continued HCQ post-ESRD were more likely to be followed by a rheumatologist (26 [87%] vs 17 [61%], p=0.024), had a higher frequency of documented arthritis (10 [32%] vs 1 [4%], p=0.005), CNS manifestations (6 [20%] vs 1 [4%], p=0.055), and concurrent immunosuppressive medication use (22 [71%] vs 12 [43%], p=0.029).Conclusions: Lupus activity may persist after the development of ESRD. New onset arthritis, lupus-related rash, CNS manifestations, low complement and elevated anti-dsDNA may develop. HCQ may be underutilized in patients with evidence of active disease pre- and post ESRD. Careful clinical and serological monitoring for signs of active disease and frequent rheumatology follow up is advised in SLE patients both, pre and post-ESRD.
Knowledge and attitudes among preschools staff in Shanghai, China, regarding epilepsy
Authors: Qiu Liyan , Shen Lixiao , Wang Junli , Ren Fang , Xu Mingyu , Jiang Fan , Sheng Xiaoyang , Li Fei , Li Feng
Published: September 2020

Background Epilepsy is one of the most common neurological problems among children. The aim of this survey was to assess the knowledge and attitude among preschool staff in Shanghai regarding epilepsy.Methods A cross-sectional survey was carried out among the staff at selected preschools. A stratified random sampling method was first used to identify suitable subjects. Data were obtained using a self-completed questionnaire. A standardized collection of demographic information was performed, and participants were given a questionnaire about their knowledge and attitudes regarding epilepsy.Results A total of 1069 subjects completed the questionnaire. In this survey, 387 (36.2%) staff members had previously participated in related training. 17.6% of teachers knew how to provide appropriate first aid for seizures. Correct responses regarding first aid for seizures, such as laying the person on his or her side (24.9%), moving harmful objects out of the way (20.7%), protecting the head (36.1%), waiting until the seizure ends (7.9%), and dialing the emergency number (40.1%), were low. The staff members had different attitudes towards children with epilepsy: some subjects had a positive attitude, some had a negative attitude.Conclusions The level of first-aid knowledge among preschool staff in Shanghai relevant to epilepsy was low. There is an urgent need to educate staff about epilepsy and appropriate first-aid practices for seizures.
Three-dimensional Multi-site Random Access Photostimulation (3D-MAP)
Authors: Xue Yi , Waller Laura , Adesnik Hillel , Pégard Nicolas
Published: September 2020

Optical control of neural ensemble activity has been crucial for understanding brain function and disease, yet no technology can achieve optogenetic control of very large numbers of neurons at extremely fast rates over a large volume. State-of-the-art multiphoton holographic optogenetics requires high power illumination that only address relatively small populations of neurons in parallel. Conversely, one-photon holographic techniques can stimulate more neurons but with a trade-off between resolution and addressable volume. We introduce a new one-photon light sculpting technique, termed Three-Dimensional Multi-site random Access Photostimulation (3D-MAP), that simultaneously overcomes all these limitations by dynamically modulating light in both the spatial and angular domain at multi-kHz rates. Electrophysiological measurements confirm that 3D-MAP achieves high spatial precision in vitro and in vivo. Using 3D-MAP, we then interrogate neural circuits with 3D multi-site illumination with high resolution over a large volume of intact brain that existing techniques cannot achieve.
Decomposing socio-economic inequality for routine medical check-ups among older adults in India
Authors: Srivast Shobhit , Patel Ratna , Chauhan Shekhar , Kumar Pradeep , Gupte Samriddhi S , Bansod Dhananjay W.
Published: September 2020

BackgroundRoutine medical check-ups not only reduce the health-care costs over time by detecting potentially life-threatening health conditions at an early stage but also reduces the risk of getting sick and thereby increasing the life span and improving overall health. Therefore, this study examined the prevalence and factors associated with medical check-ups among older adults in India.MethodsThe study utilized data from Building a Knowledge Base on Population Aging in India(BKPAI). The routine medical check-up is the outcome variable of this study. Multivariate analysis has been implemented to fulfil the objectives of the study. Concentration index and decomposition analysis were carried out to examine observed socio-economic inequality in the routine medical check-ups.ResultsNearly one-fourth (23.1%) of the older adults were undergoing the routine medical check-up. Older adults with below five years (OR, 1.31; CI: 1.13-1.51), 6 to 10 years (OR, 1.36; CI: 1.16-1.60), and 11+ years of schooling (OR, 2.02; CI: 1.6-2.54) were significantly more likely to go for routine medical check-ups than illiterate older adults. The concentration Index value of 0.19 depicts the pro-rich inequality in health check-ups among older adults. Furthermore, the results from the decomposition analysis revealed that the wealth quintile of the household contributed nearly 57 percent to the observed socio-economic inequality in the prevalence of routine medical check-up. Education and working status of older adults made a substantial contribution to the inequalities in routine medical check-ups and explained 16.9 percent, and 4.2 percent of the total inequality, respectively.ConclusionsFrom a policy perspective, at first, there is a dire need to spread awareness about the usefulness of routine medical check-ups among older adults. Further, this study reflects the association between education and routine medical check-up, and therefore there is a need to promote literacy at the grass-root level; also, it is recommended to promote health literacy among the older adults. A low level of medical check-up among older adults in rural areas could be reduced by offering free health check-ups regularly. Furthermore, the care of the elderly needs to be prioritized while policy formulation.