bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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.