bluuebunny/crossref_metadata_2025 huggingface dataset:
Transient Dynamical-Thermal-Optical System Modeling and Simulation
Authors: Hahn Luzia , Eberhard Peter
Published: December 2020

In modern high resolution optical systems like astronomical telescopes or lithographic objectives, performance degradations can be caused by various disturbances. Holistic optical system simulation is required to predict the performance or the high precision systems. In this paper a method for transient dynamical-thermal-optical system modeling and simulation is introduced. Thereby, elastic deformation, rigid body motion, and mechanical stresses due to dynamical excitation are calculated using elastic multibody system simulation and temperature changes are determined using thermal finite element analysis. The deformation, the motion, and the mechanically and thermally induced stress index changes are then considered in a gradient-index ray tracing. Finally, the presented method is applied in a dynamical-thermal single lens system.
Chern-Simons Topology Geometrics for the generation of the RoccustyrnaTM molecule, a ligand targeting COVID-19-SARS-COV-2 SPIKE D614G binding sites
Authors: Grigoriadis Ioannis
Published: December 2020

SARS coronavirus 2 (SARS-CoV-2) encoding a SARS-COV-2 SPIKE D614G mutation in the viral spike (S) protein predominate over time in locales where it is found, implying that this change enhances viral transmission. It has also been observed that retroviruses pseudotyped with SG614 infected ACE2-expressing cells markedly more efficiently than those with SD614. The availability of newer modeling techniques, powerful computational resources, and good-quality data have made it possible to generate reliable predictions for new chemical entities, impurities, chemicals, natural products, and a lot of other substances fuelling further development and growth of the field to balance the trade-off between the molecular complexity and the quality of such predictions that cannot be obtained by any other method. In this article, we effectively use a decision tree to obtain an optimum number of small chemical active chemical features from a collection of thousands of them utilizing a shallow neural network and jointly free energy cumulative feature ranking method with decision tree taking both network parameters and input toxicity benchmark features into account. In this paper, we strongly combine methods that are simple in machine learning characteristics, efficient in computing resource usage, and powerful to achieve very high accuracy levels for the in-silico generation of the AI-Quantum designed molecule the RoccustyrnaTM small molecule, a multi-targeting druggable scaffold (1Z)-2‐{((2S,3S,5R)‐5‐ (2‐amino‐6‐oxo‐6,9‐dihydro‐1H‐purin‐9‐yl)‐3‐hydroxyoxolan‐2‐yl)methylidene}‐2‐cyano‐1‐({((2S,4R,5R)‐2‐methyl‐2‐(methylamino)‐1,6‐diazabicyclo(3.2.0)heptan‐4‐yl)oxy}imino)‐1lambda5,2lambda5‐azaphosphiridin‐1‐ylium.targeting the COVID-19-SARS-COV-2 SPIKE D614G mutation using Chern-Simons Topology Euclidean Geometric in a Lindenbaum-Tarski generated QSAR automating modeling and Artificial Intelligence-Driven Predictive Neural Networks.
Plasma LPA protein levels are associated with postoperative persistent pulmonary hypertension in children with ventricular septal defects
Authors: Yu Di , Zang Xiaodong , Wang Ruonan , Mo Xuming
Published: December 2020

Persistent pulmonary arterial hypertension after ventricular septal defect surgery (VSD-PAH) has a severe consequence, and plasma protein profiles in VSD-PAH are unknown.Pulmonary arterial hypertension associated with congenital heart disease (CHD-PAH) has serious consequence and plasma protein profiles in CHD-PAH are unknown. We aimed to reveal the differential plasma proteins in 272 CHD patients with or without PAH. Various types of CHD-PAH were studied. Differential plasma proteins were first detected by iTRAQ proteomic technology and those with significant clinical relevance were selected for further ELISA validation in new cohort of patients. Among the 190 differential plasma proteins detected by iTRAQ, carbamoyl-phosphate synthetase I (CPSI, related to urea cycle and endogenous nitric oxide production) and complement factor H-related protein 2 (CFHR2, related to complement system and coagulant mechanism) were selected for further ELISA validation in new cohort of 152 patients. Both CPSI and CFHR2 were down-regulated with decreased plasma levels (p < 0.01). Thus, we for the first time in CHD-PAH patients identified a large number of differential plasma proteins. The decreased CPSI expression in CHD-PAH patients may reveal a mechanism related to endogenous nitric oxide and the decrease of CFHR2 protein may demonstrate the deficiency of the immune system and coagulation mechanism. The findings may open a new direction for translational medicine in CHD-PAH with regard to the diagnosis and progress of the disease.
Antioxidant therapy in a patient with Hyperprolinemia type I presented with mild neuromotor retardation and speech disturbance
Authors: Ersoy Melike , Yılmaz Semra , Ceylaner Serdar
Published: December 2020

Background: Hyperprolinemia type 1 (HPI) is an autosomal recessive inborn disease caused by mutations/deletions of PRODH gene, which is located on chromosome 22q11. The clinic spectrum involves mainly delayed psychomotor development, mild-to-severe mental retardation, neuropsychiatric symptoms and epilepsy. Although HPI can easily be diagnosed in patients undergoing metabolic screening tests, there is no effective therapy protocol in use. There are studies showing that it does most of its clinical findings by disrupting mitochondria function. Case report: We present a long-term follow-up of a four-year-old girl with mild neuromotor retardation and speech disturbance, diagnosed with HPI and treated with antioxidant therapy (vitamin C, CoenzymeQ10, vitamin B complex and L-carnitine) for six years. It has been shown that antioxidant therapy decreases proline levels properly and provides clinical improvement.
The association between hypoglycemia and glycemic variability in elderly patients with type 2 diabetes: cross-sectional study
Authors: Handa Takahisa , Nakamura Akinobu , Miya Aika , Nomoto Hiroshi , Kameda Hiraku , Cho Kyu Yong , Nagai So , Yoshioka Narihito , Miyoshi Hideaki , Atsumi Tatsuya
Published: December 2020

BackgroundThis study aimed to explore predictive factors of time below target glucose range (TBR) ≥ 1% among patients’ characteristics and glycemic variability (GV) indices using continuous glucose monitoring data in elderly patients with type 2 diabetes.MethodsWe conducted a prospective observational study on 179 (71 female) Japanese outpatients with type 2 diabetes aged ≥ 65 years. The characteristics of the participants with TBR ≥ 1% were evaluated by multivariate logistic regression analysis. Receiver-operating characteristic (ROC) curve analyses of GV indices, comprising coefficient of variation (CV), standard deviation, and mean amplitude of glycemic excursions, were performed to identify the optimal index for the identification of patients with TBR ≥ 1%.ResultsIn the multivariate logistic regression analysis, none of the clinical characteristics, including HbA1c and C-peptide index, were independent markers for TBR ≥ 1%, while all three GV indices showed significant associations with TBR ≥ 1%. Among the three GV indices, CV showed the best performance based on the area under the curve in the ROC curve analyses.ConclusionsAmong elderly patients with type 2 diabetes, CV reflected TBR ≥ 1% most appropriately among the GV indices examined.Trial registration: UMIN-CTR: UMIN000029993. Registered 16 November 2017
Protein engineering in the big data era: harnessing near-redundant structural data
Authors: Flores Samuel Coulbourn , Alexiou Athanasios , Glaros Anastasios
Published: December 2020

Motivation: Predicting the effect of mutations on protein-protein interactions is important for relating structure to function, as well as for in silico affinity maturation. The effect of mutations on protein-protein binding energy (ΔΔG) can be predicted by a variety of atomic simulation methods involving full or limited flexibility, and explicit or implicit solvent. Methods which consider only limited flexibility are naturally more economical, and many of them are quite accurate, however results are dependent on the atomic coordinate set used. In this work we perform a sequence and structure based search of the Protein Data Bank to find additional coordinate sets and repeat the calculation on each. Results: . We improve increase precision and Positive Predictive Value, and decrease Root Mean Square Error and higher Positive Predictive Value, compared to using single structures. Given the ongoing growth of near-redundant structures in the Protein Data Bank, our method will only increase in applicability and accuracy. Availability: Public web server at biodesign.scilifelab.se
The role of economic, educational and social resources in supporting the use of digital health technologies by people with T2D: a qualitative study
Authors: Turnbull Sophie , Lucas Patricia , Hay Alastair D , Cabral Christie
Published: December 2020

BackgroundType 2 Diabetes (T2D) is a common chronic disease, with socially patterned incidence and severity. Digital self-care interventions have the potential to reduce health disparities, by providing personalised low-cost reusable resources that can increase access to health interventions. However, if under-served groups are unable to access or use digital technologies, Digital Health Technologies (DHTs) might make no difference, or worse, exacerbate health inequity. Study aimsTo gain insights into how and why people with T2D access and use DHTs and how experiences vary between individuals and social groups.MethodsA purposive sample of people with experience of using a DHT to help them self-care for T2D were recruited through diabetes and community groups. Semi-structured interviews were conducted in person and over the phone. Data were analysed thematically.ResultsA diverse sample of 21 participants were interviewed. Health care practitioners were not viewed as a good source of information about DHTs that could support T2D. Instead participants relied on their digital skills and social networks to learn about what DHTs are available and helpful. The main barriers to accessing and using DHT described by the participants were availability of DHTs from the NHS, cost and technical proficiency. However, some participants described how they were able to draw on social resources such as their social networks and social status to overcome these barriers. Participants were motivated to use DHTs because they provided self-care support, a feeling of control over T2D, and personalised advice or feedback. The selection of technology was also guided by participants’ preferences and what they valued in relation to DHTs and self-care support, and these in turn were influenced by age and gender.ConclusionThis research indicates that low levels of digital skills and high cost of digital health interventions can create barriers to the access and use of DHTs to support the self-care of T2D. However, social networks and social status can be leveraged to overcome some of these challenges. If digital interventions are to decrease rather than exacerbate health inequalities, these barriers and facilitators to access and use must be considered when DHTs are developed and implemented.
Predictors of resignation and sick leave after cancer dianosis among Japanese breast cancer survivors: a cross-sectional study
Authors: Mitsui Kiyomi , Endo Motoki , Imai Yuya , Ueda Yuito , Ogawa Hiroko , Muto Go , Yan Yan , Deshpande Gautam A. , Terao Yasuhisa , Takeda Satoru , Tanigawa Takeshi , Nishimura Katsuji , Hayashi Kazuhiko , Saito Mitsue , Kokaze Akatsuki
Published: December 2020

Background: In Japan, 55.5% of breast cancer survivors (BCSs) are of working age, so various perspectives regarding return to work (RTW) after cancer diagnosis need to be considered. Therefore, this study aimed to clarify the risk factors for resignation and taking sick leave (SL) among BCSs in continued employment at the time of diagnosis.Methods: A web-based retrospective cross-sectional survey was conducted on BCSs using data from a 2018 Japanese national research project (Endo-Han) commissioned by the Ministry of Health, Labour and Welfare of Japan. The subjects were women aged 18–69 years who had been diagnosed with breast cancer for the first time at least 1 year previously. The risk factors for resignation and taking SL after breast cancer diagnosis, including age at diagnosis, education level, cancer stage, surgery, chemotherapy, radiotherapy, employment status, and occupational type, were then analyzed using a logistic regression model.Results: In total, 40 (14.9%) of 269 BCSs quit their jobs at least 1 year after being diagnosed with breast cancer. The results of the multivariable analysis indicated that lower education level (odds ratio [OR]: 3.802; 95% confidence interval [CI]: 1.233–11.729), taking SL (OR: 2.514; 95%CI: 1.202–5.261), and younger age at diagnosis (OR: 0.470; 95%CI: 0.221–0.998) were predictors of resignation. Of 229 patients who continued working, SL was taken by 72 (31.4%). In addition, undergoing surgery was found to be a predictor of taking SL (OR: 8.311; 95%CI: 1.007–68.621).Conclusions: In total, 40 (14.9%) of 269 BCSs quit their jobs at least 1 year after being diagnosed with breast cancer. The results of this study indicated that younger age, lower education level, and taking SL were predictors of resignation after breast cancer diagnosis.
Patient-reported Outcomes in Young Adults with Osteonecrosis Secondary to Developmental Dysplasia of the Hip
Authors: Marks Avi , Cortina-Borja Mario , Maor Dror , Hashemi-Nejad Aresh , Roposch Andreas
Published: December 2020

Background: Osteonecrosis of the femoral head is a common complication in the treatment of developmental dysplasia of the hip (DDH). While functional outcomes of affected patients are good in childhood, it is not clear how they change during the transition to young adulthood. This study determined the relationship between osteonecrosis and hip function, physical function and health status in adolescents and young adults.Methods: We performed a cross-sectional study of 169 patients with a mean age of 19.7 ± 3.8 years with and without osteonecrosis following an open or closed reduction (1995-2005). We also performed a separate longitudinal evaluation of an historical cohort of 54 patients with osteonecrosis, embedded in this sample. All completed patient-reported outcome measures in 2015/2016 to quantify hip function (maximum score 100); physical function (maximum score 100); and general health status (maximum score 1). We graded all radiographs for subtype of osteonecrosis (Bucholz-Ogden); acetabular dysplasia (centre-edge angle); subluxation (Shenton’s line); and osteoarthritis (Kellgren-Lawrence). Analyses were adjusted for the number of previous surgical procedures on the hip and for the severity of residual hip dysplasia.Results: In 149 patients (186 hips) with and without osteonecrosis, the mean differences (95% confidence interval) in hip function, physical function and quality of life were -4.7 (-10.26, 0.81), -1.03 (-9.29, 7.23) and 0.10 (-1.15, 1.18), respectively. Adjusted analyses stratified across types of osteonecrosis showed that only patients with Bucholz-Odgen grade III had reduced hip function (p<0.01) and physical function (p<0.05) but no difference in health-related quality of life when compared to no osteonecrosis. Conclusion: Osteonecrosis secondary to DDH is a relatively benign disorder in adolescents and young adulthood. Affected patients demonstrated minimal physical disability, a normal quality of life but reduced hip function.
Prognostic value of the neutrophil-to-lymphocyte ratio and primary tumor location in patients with EGFR-mutated metastatic non-small cell lung cancer treated with TKIsNote: We found that we got a wrong results in the previous article. So, we checked our collected database and calculated again and corrected now.
Authors: Xie Xueqi , Li Xiaolin , Tang Wenjie , Chen Jinlong , Li Minghuan , Xie Peng , Yu Jinming
Published: December 2020

Background: Targeted therapy with the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) has improved the field of metastatic non-small cell lung cancer treatment. Higher neutrophil-to-lymphocyte ratio (NLR) and lower relative lymphocyte counts as inflammatory indicators and associated with worse overall survival and progression free survival (PFS) in several tumor types. Few studies focused on these inflammation markers in field of TKIs eras. Methods: Patients with advanced EGFR mutation NSCLC treated with TKIs were included. Pre-treatment NLR means neutrophil to lymphocyte ratio measured in peripheral blood within one week before treating with TKIs. The baseline clinical characteristics of each group were compared by chi-square and t tests. Cox regression analyses were used to evaluate prognostic value of peripheral blood parameters on progression free survival (PFS). All prognostic factors were explored with multivariable regression. Results: We retrospectively analyzed 221 patients with metastatic NSCLC harboring exon 19 deletion, 21 L858R or rare mutation and receiving TKIs. Finally, a total of 190 patients were analyzed. The optimal cutoff values for pretreatment absolute lymphocyte count (Lym), lymphocyte percentage (Lym%), absolute neutrophil count (Neu), the percentage of neutrophil granulocytes (Neu%) and NLR were 1.625 , 18.8%, 3.675 , 51.8% and 4.965, respectively. Patients with high neutrophil percent (18.8 months vs 13.0 months, P=0.003), absolute neutrophil counts (12.0 months vs 14.5 months, P=0.014) and NLR (7.0 months vs 15.2 months, P<0.001, 1-year PFS Rate, 38.4%, respectively) had worse PFS. In contrast, patients with high absolute lymphocyte counts (16.5 months vs 13.0 months, P=0.012) and lymphocyte percent (15.3 months vs 8.8 months, P<0.001) had a better progression-free-survival. Besides, tumor location is also an important factor for prognosis (14.3 months vs 11.6 months, P=0.003). On multivariate analysis, NLR and primary tumor location were both identified as independent and significantly risk indicators for worse PFS. Conclusion: NLR and primary location are both independent prognostic factors for PFS in patients with metastatic EGFR mutated lung tumor. Whether or not NLR and primary location could be useful markers in efficacy prediction of TKIs in advanced NSCLC calls for further investigation. KEYWORDS: Epidermal growth factor; NSCLC; TKI; Primary location; NLR; PFS
Craniofacial morphology/phenotypes influence on mandibular range of movement in the design of a mandibular advancement device
Authors: Sanz Pedro Mayoral , Reyes Mariano Garcia , Torras Alex Bataller , Castillo JA Cabrera , Lagravere Manuel
Published: December 2020

Background. The mandibular opening path movements have different directions according to the craniofacial morphology of the patient but always downward and backward, therefore increasing the collapse of the upper airway. The aim of this work is to determine if there is a relationship between the craniofacial morphology and the mandibular movement to help understand the impact on the mandibular position. Methods. 52 students with full permanent dentition aged 19 to 23 years (mean 21.3 SD 1.7; 29 females and 23 males), participated in the study. Each subject had a lateral cephalometric radiograph taken. The opening angle was determined for two levels of vertical openings at 5 and 10 mm.Results. The opening angle showed a greater variability between subjects ranging from 63.15 to 77.08 for 5 mm angle and from for 61.65 to 75.72 for the 10 mm angle. Differences of facial phenotypes was evident when comparing the individual dissoccluding angle of the low angle horizontal pattern and high angle vertical pattern.Conclusions. The opening angle is related to craniofacial morphology with higher vertical anterior and shorter anteroposterior faces having a more horizontal path of mandibular movement than shorter vertical anterior and longer anteroposterior subjects who have a more vertical path.
Evaluating the genetic effects of sex hormone traits on the development of mental traits: a polygenic score analysis and gene-environment-wide interaction study in UK Biobank cohort
Authors: Liang Xiao , Cheng ShiQiang , Ye Jing , Chu XiaoMeng , Wen Yan , Liu Li , Qi Xin , Jia YuMeng , Zhang Feng
Published: December 2020

Objective: To evaluate the genetic effects of sex hormone traits on the development of mental traits in middle-aged adults.Methods: The SNPs associated with sex hormone traits were derived from a two-stage genome-wide association study (GWAS). Four sex hormone traits were selected in the current study, including sex hormone-binding globulin (SHBG), testosterone, bioavailable testosterone and estradiol. The polygenic risk score (PRS) of sex hormone traits were calculated from individual-level genotype data of the United Kingdom (UK) Biobank cohort. We then used logistic and linear regression models to assess the associations between individual PRS of sex hormone traits and the frequency of alcohol consumption, anxiety, intelligence and so on. Finally, gene-environment-wide interaction study (GEWIS) was performed to detect novel candidate genes interacting with the sex hormone traits on the development of fluid intelligence and the frequency of smoking and alcohol consumption by PLINK2.0.Results: We observed positive association between SHBG and the frequency of alcohol consumption (b=0.0101, p=3.84×10–11) in middle-aged males and females. In addition, estradiol was positively associated with the frequency of alcohol consumption (b=0.0128, p=1,96×10–8) in middle-aged males. Moreover, bioavailable testosterone was associated with the fluid intelligence (b=-0.0136, p=5.74×10-5) in middle-aged females. Finally, GEWIS identified one significant loci, Tenascin R (TNR) (rs34633780, p=3.45×10–8) interacting with total testosterone for fluid intelligence.Conclusion: Our study results support the genetic effects of sex hormone traits on the development of intelligence and the frequency of alcohol consumption in middle-aged adults in UK.
PCNA-associated factor (KIAA0101/PCLAF) overexpression and gene copy number alterations in hepatocellular carcinoma tissues
Authors: Tantiwetrueangdet Anchalee , Panvichian Ravat , Sornmayura Pattana , Leelaudomlipi Surasak , Macoska Jill A.
Published: December 2020

Background: PCNA-associated factor, the protein encoded by the KIAA0101/PCLAF gene, is a cell-cycle regulated oncoprotein that regulates DNA synthesis, maintenance of DNA methylation, and DNA-damage bypass, through the interaction with the human sliding clamp PCNA. KIAA0101/PCLAF is overexpressed in various cancers, including hepatocellular carcinoma (HCC). However, it remains unknown whether KIAA0101/PCLAF overexpression is coupled to gene amplification in HCC.Methods: KIAA0101/PCLAF mRNA expression levels were assessed by quantitative real-time PCR in 40 pairs of snap-frozen HCC and matched-non-cancerous tissues,KIAA0101/PCLAF gene copy numbers were evaluated by droplet digital PCR (ddPCR) in 36 pairs of the tissues, and protein expression was detected by immunohistochemistry (IHC) in 81 pairs of formalin-fixed paraffin-embedded (FFPE) tissues. The KIAA0101/PCLAF gene copy number alteration and RNA expression was compared by Spearman correlation, and the relationship between KIAA0101 protein expression and other clinicopathological parameters was evaluated using Chi-square test.Results: Our results demonstrated that KIAA0101/PCLAF mRNA levels were significantly higher in HCC than in the matched-non-cancerous tissues (p<0.0001), and high KIAA0101/PCLAF mRNA levels in HCC were associated with poor patient survival. The KIAA0101/PCLAF gene was not amplified in HCC and KIAA0101/PCLAF gene copy numbers were not associated with KIAA0101/PCLAF transcript levels. KIAA0101 protein was overexpressed in the majority of HCC tissues (77.8%) but was not be detectable in matched-non-cancerous tissues. Significant correlations between the expression of KIAA0101 protein and p53 tumor suppressor protein (p=0.002), and Ki-67 proliferation marker protein (p=0.017) were found. However, KIAA0101 protein levels were not correlated with patient age, tumor size, or the expression of AFP and HBsAg.Conclusions: KIAA0101/PCLAF mRNA and protein overexpressionis frequently observed in HCC but without concurrent KIAA0101/PCLAF gene amplification. Significant correlations between the expression of KIAA0101 protein and p53 and Ki-67 proteins were observed in this study. Thus, detection of KIAA0101/PCLAF mRNA/protein might be used, along with the detection of p53 and Ki-67 proteins, as potential biomarkers to select candidate patients for further studies of novel HCC treatment related to these targets.
COVID-19: A National Survey on Perceived Level of Knowledge, Attitude and Practice among Frontline Healthcare Workers in Nepal
Authors: Tamang Nira , Rai Punam , Dhungana Siddhartha , Sherchan Binod , Shah Bikash , Pyakurel Prajjwal , Rai Saroj
Published: December 2020

Background The aim of this study was to determine the knowledge, attitude and practice(KAP) regarding the COVID-19 among frontline healthcare workers (F-HCWs) working at different hospitals in Nepal and to identify the factors significantly associated with KAP.Methods We used a web-based survey, and a convenience sampling method was adopted to collect data from 603 F-HCWs working at different hospitals in Nepal during the first week of June 2020. A self-administered questionnaire was utilized to assess the KAP perceived by the F-HCWs. It was divided into 4-parts consisting of 30-items, demographic characteristics (10-items), knowledge (10-items), attitude (5-items), and practice (5-items). It consisted of both multiple-choice questions and Likert scale items questionnaire. Results Among the participants, 76% reported adequate knowledge, 54.7% reported positive attitude, and 78.9% reported appropriate practice. Statistically significant differences regarding the perceived level of knowledge among F-HCWs were observed among independent variables, including age, gender, level of education, marital status, profession, work experience, source of information, infection prevention and control (IPC) training, and online course(p<0.05). Similarly, statistically significant differences regarding the attitude among F-HCWs were observed among independent variables, including age, gender, level of education, profession, and online course(p<0.05). Moreover, only 2-independent variables, including the profession and online course, showed statistically significant differences with practice(p<0.05). Pearson correlation analysis showed a significant association between knowledge, attitude and practice at the level of p=0.01. The factors significantly associated with adequate knowledge were male gender, nurse and doctor, websites and IPC training. Similarly, factors significantly associated with positive attitude were online course related to COVID-19 only. Moreover, factors significantly associated with appropriate practice were master’s degree or above and online course related to COVID-19.Conclusions F-HCWs reported adequate overall knowledge with a positive attitude and adopted the appropriate practice. The experienced F-HCWs with higher education and who received IPC training and online course regarding COVID-19 had better KAP. So, the stakeholders must arrange the educational programs and training for F-HCWs for better preparedness tackling with COVID-19.
Pre-inhalation of hydrogen-rich gases protect against caerulein-induced mouse acute pancreatitis while enhance the pancreatic Hsp60 protein expression
Authors: Li Kun , Yin Hongling , Duan Yi , Lai Peizhen , Cai Yanchen , Wei Youzhen
Published: December 2020

Background: Acute pancreatitis (AP) lacks targeted prevention and treatment measures. Some key points in the pathogenesis of AP remain unclear, such as early activation of pancreatic enzymes. Several recent reports have shown the protective effect of hydrogen on several AP animal models, and the mechanism is related to antioxidant activity. Heat shock protein 60 (Hsp60) is known to accompany pancreatic enzymes synthesis and secretion pathway of in pancreatic acinar cells, while role of hsp60 in AP remains a topic. Aim of this study was to investigate effect of hydrogen pretreatment on AP and the mechanisms, focusing on pancreatic oxidative stress and Hsp60.Methods: 80 mice were randomly assigned into four groups: HAP group, AP group, HNS group, and NS group and each group were set 3 observation time point as 1h, 3h and 5h (n=6- 8). Mouse AP model was induced by intraperitoneal injection of 50μg/kg caerulein per hour for 6 injections both in AP and HAP groups, and mice in NS group and HNS group given normal saline (NS) injections at the same way as control respectively. Mice in HAP group and HNS group were treated with hydrogen-rich gases inhalation for 3 days before the first injection of caerulein or saline, while mice in AP group and NS group in normal air condition. Histopathology of pancreatic tissue, plasma amylase and lipase, plasma IL-1 and IL-6, pancreatic glutathione (GSH) and malondialdehyde (MDA), and Hsp60 mRNA and protein expression were investigated. Comparisons were made by one-way analysis of variance.Results: The pancreatic pathological changes, plasma amylase and lipase activity, and the increase of plasma IL-1 and IL-6 levels in AP mice were significantly improved by the hydrogen-rich gases pretreatment, Meanwhile, the pancreatic GSH content increased and the pancreatic MDA content decreased. And, the hydrogen-rich gases pretreatment improved the Hsp60 protein expression in pancreatic tissues of AP mice at 1h and 5h. Conclusions: Pre-inhalation of hydrogen-rich gases have a good protective effect on AP mice, and the possible mechanisms of reduced oxidative stress and the early increased pancreatic Hsp60 protein deserve attention.
Exploring wealth-related inequalities in maternal and child health coverage in Latin America and the Caribbean
Authors: Colomé-Hidalgo Manuel , Campos Juan Donado , De Miguel Ángel Gil
Published: December 2020

Background. Maternal and child health have shown important advances in the world in recent years. However, national averages indicators hide large inequalities in access and quality of care in population subgroups. We explore wealth-related inequalities affecting health coverage and interventions in reproductive, maternal, newborn, and child health in Latin America and the Caribbean.Methods. We analyzed representative national surveys from 15 countries conducted between 2001 and 2016. We estimated maternal-child health coverage gaps using the Composite Coverage Index – a weighted average of interventions that include family planning, maternal and newborn care, immunizations, and treatment of sick children. We measured absolute and relative inequality to assess gaps by wealth quintile. Pearson’s correlation coefficient was used to test the association between the coverage gap and population attributable risk.Results. The Composite Coverage Index showed patterns of inequality favoring the wealthiest subgroups. In eight countries the national coverage was higher than the global median (78.4%; 95% CI: 73.1-83.6) and increased significantly as inequality decreased (Pearson r = 0.9; p <0.01).Conclusions. There are substantial inequalities between socioeconomic groups. Reducing inequalities will improve coverage indicators for women and children. Additional health policies, programs, and practices are required to promote equity.
Can the Xpert MRSA/SA BC assay be used as an antimicrobial stewardship tool? A prospective assay validation and descriptive impact assessment study in a South African setting
Authors: Reddy Kessendri , Whitelaw Andrew Christopher
Published: December 2020

Background: Positive blood cultures showing Gram positive cocci in clusters signifies either Staphylococcus aureus or the less-virulent coagulase-negative staphylococci. Rapid identification and methicillin susceptibility determination with the Xpert MRSA/SA BC assay can improve management of S. aureus bloodstream infection and reduce inappropriate antibiotic use. Methods:We prospectively evaluated the Xpert MRSA/SA BC assay in comparison with culture, on samples referred to our laboratory in the Western Cape, South Africa. We interviewed attending clinicians upon culture result availability, to assess antibiotic choices and estimate potential impact of the assay.Results: Of the 231 samples included, there was 100% concordance between the Xpert MRSA/SA BC assay and culture (methicillin-resistant S. aureus 15/15, methicillin-susceptible S. aureus 42/42, coagulase-negative staphylococci 170/170). Time to final result could be reduced by approximately 30 hours with the assay. Of the 178 patients with adequate antibiotic history, optimisation of antistaphylococcal therapy could have occurred more than one day sooner in 68.9% with S. aureus bloodstream infection (31/45, 95% CI 53.2-81.4%). Six of the 11 patients with methicillin-resistant S. aureus bloodstream infection (54.5%) could have received anti-MRSA cover sooner. Fifty-four days of antibiotic therapy could have been spared, equating to 0.3 days (95% CI, 0.2-0.4) saved per patient, driven by broad-spectrum beta-lactams (32 days, in 18.0% of the cohort).Conclusion:This assay has potential as an antimicrobial stewardship tool; costing and impact on clinical outcome in patients with S. aureus bloodstream infection should be assessed.
Violence and depression among pregnant women in Egypt
Authors: Ghoneim Hanan M. , Elprince Mohamed , Ali Tamer Yehia M. , Gharieb Waleed , Ahmed Amal
Published: December 2020

Background: Depression is a serious mental health disorder that might affect women in the childbearing period. Incidences increase during pregnancy as well as after delivery. Its association with intimate partner violence has been reported in many countries. Data about this sensitive issue are lacking in Egypt. The aim of the study was to determine the relation between intimate partner violence and depression during pregnancy.Methods: This was a case control study conducted at the the outpatient clinics in Suez Canal University hospitals, from January 2019 to March 2020. The study included two groups, the study group included women exposed to violence during the current pregnancy and a control one included women with no history of violence. Women were asked to complete the Arabic validated NorVold Domestic Abuse Questionnaire. Depression was evaluated using the Arabic validated form of the Edinburgh Postnatal Depression Scale. The main outcome measure was to assess the association between intimate partner violence and depression.Results: Both groups were matched in their demographic characters. Emotional violence was the most common reported pattern among women exposed to intimate partner violence 87.9% (139/158). There was a significant difference between women exposed to violence and those who were not exposed to violence in the total depression scores (13.63 ± 5.47 and 10.65 ± 5.44, respectively with a p value <0.001). Emotional and sexual violence had significant roles as risk factors for depression during pregnancy in single regression or after control of other confounders. Conclusion: There was a strong association between intimate partner violence and depression during pregnancy with variable rates that differ according to the economic state of the countries.
A comparison of methods for interpreting random forest models of genetic association in the presence of non-additive interactions.
Authors: Orlenko Alena , Moore Jason H
Published: December 2020

Background: Non-additive interactions among genes are frequently associated with a number of phenotypes, including known complex diseases such as Alzheimer’s, diabetes, and cardiovascular disease. Detecting interactions requires careful selection of analytical methods, and some machine learning algorithms are unable or underpowered to detect or model feature interactions that exhibit non-additivity. The Random Forest method is often employed in these efforts due to its ability to detect and model non-additive interactions. In addition, Random Forest has the built-in ability to estimate feature importance scores, a characteristic that allows the model to be interpreted with the order and effect size of the feature association with the outcome. This characteristic is very important for epidemiological and clinical studies where results of predictive modeling could be used to define the future direction of the research efforts. An alternative way to interpret the model is with a permutation feature importance metric which employs a permutation approach to calculate a feature contribution coefficient in units of the decrease in the model’s performance and with the Shapely additive explanations which employ cooperative game theory approach. Currently, it is unclear which Random Forest feature importance metric provides a superior estimation of the true informative contribution of features in genetic association analysis. Results: To address this issue, and to improve interpretability of Random Forest predictions, we compared different methods for feature importance estimation in real and simulated datasets with non-additive interactions. As a result, we detected a discrepancy between the metrics for the real-world datasets and further established that the permutation feature importance metric provides more precise feature importance rank estimation for the simulated datasets with non-additive interactions. Conclusions: By analyzing both real and simulated data, we established that the permutation feature importance metric provides more precise feature importance rank estimation in the presence of non-additive interactions.
Electronic Reporting of Integrated Disease Surveillance and Response: Lessons learned from Northeast, Nigeria, 2019.
Authors: Ibrahim Luka Mangveep , Okudo Ifeanyi , Stephen Mary , Ogundiran Opeayo , Pantuvo Jerry Shitta , Oyaole Daniel Rasheed , Tegegne Sisay Gashu , Khalid Abdelrahim , Ilori Elsie , Ojo Olubunmi , Ihekweazu Chikwe , Baraka Fiona , Mulombo Walter Kazadi , Lasuba Clement Lugala Peter , Nsubuga Peter , Alemu Wondimagegnehu
Published: December 2020

Background: Electronic reporting of integrated disease surveillance and response (eIDSR) was implemented in Adamawa and Yobe states, North-East of Nigeria, as an innovative strategy to improve disease reporting. Its objectives were to improve the timeliness and completeness of IDSR reporting by health facilities, prompt identification of public health events, timely information sharing, and public health action. We evaluated the project to determine whether it met its set objectives.Method: We conducted a cross-sectional study to assess and document the lessons learned from the project. We reviewed the performance of the local government areas (LGAs) on timeliness and completeness of reporting, rumors identification, and reporting on the eIDSR and the traditional paper-based system using a checklist. Respondents were interviewed online on the relevance, efficiency, sustainability, project progress and effectiveness, the effectiveness of management, and potential impact and scalability of the strategy using structured questionnaires. Data were cleaned, analyzed, and presented as proportions using an MS Excel spreadsheet. Responses were also presented as direct quotes.Results: The number of health facilities reporting IDSR increased from 103 to 228 (117%) before and after implementation of the eIDSR respectively. The timeliness of reporting was 43% in the LGA compared to 73% in health facilities implementing eIDSR. The completeness of IDSR reports in the last six months before the evaluation was ≥ 85%. Of the 201 rumors identified and verified, 161 (80%) were from the eIDSR pilot sites. The majority of the stakeholders interviewed believed that eIDSR met its predetermined objectives for public health surveillance. The benefits of eIDSR included timely reporting and response to alerts and disease outbreaks, improved timeliness, and completeness of reporting, and supportive supervision to the operational levels. The strategy helped stakeholders to appreciate their roles in public health surveillance.Conclusion: The eIDSR has increased the number of health facilities reporting IDSR, enabled early identification, reporting, and verification of alerts, improved timeliness and completeness of reports, and supportive supervision of staff at the operational levels. It was well accepted by the stakeholder as a system that made reporting easy with the potential to improve the public health surveillance system in Nigeria.
“I have SMA, SMA doesn’t have me”- A Qualitative Snapshot into the Challenges, Successes, and Quality of Life of Adolescents and Young Adults with SMA
Authors: Mazzella Allison Joy , Curry Mary , Belter Lisa , Cruz Rosangel , Jarecki Jill
Published: December 2020

Background: With the approval of three treatments for spinal muscular atrophy (SMA) and several promising therapies on the horizon, the SMA adolescent and young adult populations are expected to evolve in the coming years. It is imperative to understand this cohort as it exists today to provide optimal care and resources, as well as to assess possible treatment effects over time. In 2018, Cure SMA launched two initiatives geared towards understanding adolescents and young adults with SMA, ages 12-25. First, Cure SMA launched a Quality of Life (QoL) survey to capture quantitative and qualitative information on this specific age demographic. Concurrently, Cure SMA invited SMA-affected individuals, ages 12-25, to create a three-minute video on their everyday experiences living with SMA. An inductive thematic analysis of the free-text survey questions along with the video contest findings are reported here. Results: Eighty-five individuals — 6 type Is, 58 type IIs, and 21 type IIIs — completed the Quality of Life free-response, while six individuals participated in the SMA awareness video contest. In both settings, individuals detailed a variety of challenges, including but not limited to forming or maintaining close relationships, experiencing feelings of isolation, challenges with accessibility, independence, and dealing with the stigma of being perceived as mentally disabled. Individuals also discussed their successes, including but not limited to higher education enrollment and attendance, development of quality friendships, and perseverance through obstacles. Additionally, notably in the survey, 39% of respondents requested the creation of an SMA peer support group in efforts to connect with each other as well as collectively navigate the aforementioned challenges they face. Conclusion: Together, these findings provide a rare glimpse into the unique mindsets, challenges and motivations of SMA adolescents and young adults, via patient-reported measures instead of caregiver proxy. The adolescent and young adult age demographics assessed represent a critical transition period in life and in SMA care. No one understands the needs of an adolescent or young adult with SMA better than the individuals themselves, and it is critical to encapsulate their insights to affect change.
A retrospective survey of strabismus surgery in a tertiary eye center in northern China, 2014-2019
Authors: Wan Xiaomei , Wan Luqin , Jiang Mingming , Ding Yichao , Wang Yuan , Zhang Jing
Published: December 2020

Background To evaluate the distribution pattern and changes of strabismus surgery in northern China. Methods The records of strabismus patients at Qingdao Eye Hospital from January 2014 to December 2019 were reviewed retrospectively. The characteristics analyzed included gender, regional distribution, constituent ratio of age and type of strabismus. Changes during the periods 2014–2016 and 2017–2019 were compared and analyzed. Results A total of 5746 strabismus patients were recruited. The number of strabismus patients was relatively stable each year from 2014 to 2016 but gradually increased each year from 2017 to 2019. Of these, 51.7% (2868/5746) were male, and 48.3% (2778/5746) were female. The majority (89.8%, 5159/5746) of the patients were from Shandong Province. The statistical results of the constituent ratio of age showed that 32.4% (1860/5746) were 7–12 years old (primary school level). Patients under 12 years of age (preschool and primary school level) accounted for 60.0% (3447/5746) of all the patients. In terms of the types of strabismus, exotropia accounted for 63.5% (3650/5746), followed by esotropia and vertical rotational strabismus at 13.2% (758/5746) and 9.7% (555/5746), respectively. Intermittent exotropia was the most common type among the exotropia patients, accounting for 71.3% (2604/3650). Among the patients with intermittent exotropia, 62.5% (1627/2604) were children aged 4–12 years, and the basic type of intermittent exotropia was the main type. Four percent (231/5746) of the patients, of which adult patients comprised the main population, required reoperation.Conclusion Patients with strabismus at primary school level comprised the largest group of strabismus patients in north China. Exotropia was the most common type of strabismus, and intermittent exotropia was the most common type of exotropia. The rate of exotropia to esotropia was 5:1.
Optimal cut-off values for anthropometric indices of obesity as discriminators of metabolic abnormality in Korea: Results from a Health Examinees study
Authors: Cho Sooyoung , Shin Aesun , Choi Ji-Yeob , Park Sang Min , Kang Daehee , Lee Jong-Koo
Published: December 2020

Background: Obesity is well known as a risk factor for cardiovascular disease. We aimed to determine the performance of and the optimal cut-off value for obesity indices to discriminate the presence of a metabolic abnormality as a primary risk for cardiovascular diseases in a Health Examinees study (HEXA). Methods: The current study analyzed 134,195 participants with complete anthropometric and laboratory information in a Health Examinees study, consisting of the Korean population aged 40 to 69 years. The presence of metabolic abnormality was defined as having at least one of the following: hypertension, hyperglycemia, or dyslipidemia. The area under the receiver operating characteristic curve (AUC) and 95% confidence intervals (CIs) were calculated for body mass index (BMI), waist to hip ratio (WHR), waist to height ratio (WHtR), waist circumference (WC), and conicity index (C index). Results: AUC of metabolic abnormality was the highest for WHtR (AUC [95% CIs], 0.677 [0.672-0.683] among men; 0.691 [0.687-0.694] among women), and the lowest for the C index (0.616 [0.611-0.622] among men; 0.645 [0.641-0.649] among women) among both men and women. The optimal cutoff values were 24.3kg/m2 for BMI, 0.887 for WHR, 0.499 for WHtR, 84.4cm for WC and 1.20m3/2/kg1/2 for the C index among men, and 23.4kg/m2 for BMI, 0.832 for WHR, 0.496 for WHtR, 77.0 cm for WC and 1.18m3/2/kg1/2 for the C index among women. Conclusion: Our findings are implicated that the primary prevention of cardiovascular disease can be approached via appropriate recommendations for abdominal obesity in Korea.