bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characteristics and diversity of mutations in regulatory genes of resistance-nodulation-cell division efflux pumps in association with drug-resistant clinical isolates of Acinetobacter baumannii
Authors: Salehi Bahare , Ghalavand Zohreh , Yadegar Abbas , Eslami Gita 
Published: September 2020

Abstract
Background: This study aimed to characterize the regulation and expression of three putative resistance-nodulation-cell division (RND)-type efflux systems and their contribution to multidrug efflux in clinical isolates of Acinetobacter baumannii. Methods: Antimicrobial susceptibility testing (AST) of 95 A. baumannii isolates was determined by Kirby-Bauer disk diffusion for 18 antibiotics and minimum inhibitory concentration (MIC) of colistin was determined by broth microdilution method. Moreover, MIC of five classes of antibiotics was assessed using E-test strips in the presence and absence of phenylalanine-arginine beta-naphthylamide (PAβN). Regulatory genes of RND efflux pumps (AdeRS, AdeL, AdeN and BaeSR) were subjected to sequencing. The relative expression of adeB. adeG and adeJ genes was determined by quantitative real-time PCR (RT-PCR).Results: Overall, majority of isolates (93%) were extensively drug-resistant (XDR). In the phenotypic assay, efflux pump activity was observed in 40% of isolates against multiple antibiotics mainly tigecycline, but not to imipenem. Several amino acid substitutions were detected in the regulatory genes; except in AdeN. Of note, A136V in AdeR and G186V in AdeS were found to be associated with overexpression of their relative efflux pumps. No insertion sequences (ISs) were detected. Conclusions: Our findings outline the role of RND efflux pumps in resistance of A. baumannii against multiple antibiotics particularly tigecycline, and point out importance of a variety of single mutations in the corresponding regulatory systems. Even though it has been concluded that multidrug resistance occurs as a result of a complex sets of different resistant mechanisms
Loop electrosurgical excision procedure combined with cold coagulation for cervical intraepithelial neoplasia and adenocarcinoma in-situ: A feasible treatment with a low risk of residual/recurrent disease
Authors: Yang Eun Jung , Kim Nae Ry , Choi Ji Yeon , Kim Wook Youn , Lee Sun Joo 
Published: September 2020

Abstract
Objective This study was performed to evaluate the significance of positive resection margins (RMs) with the loop electrosurgical excision procedure combined with cold coagulation (LEEP with CC) as a definitive treatment for patients with cervical intraepithelial neoplasia (CIN) and adenocarcinoma in-situ . Methods We retrospectively reviewed 467 patients who underwent LEEP with CC. A right-angled triangular loop in a single pass followed by a CC (120°C) to the cone bed for 10 to 20 seconds was used. Pathology reports and clinical data were obtained and evaluated. Results Histopathology evaluation of LEEP tissue samples revealed the presence of CIN 1 in 69, CIN 2/3 in 366, AIS in 5 and invasive carcinoma in 16 (microinvasive squamous cell carcinoma (SCC) and invasive SCC, 13 and 3) patients. Margins were positive in 66 (14.5%) cases: 0 in CIN 1, 54 in CIN 2/3 (12.4%), 1 in AIS (20.0%) and 11 in microinvasive/invasive SCC (68.8%). Although 54 CIN2/3 patients with positive RMs did not undergo additional treatment, 1 of these (1.9%) was confirmed to have residual CIN3 at the first follow-up. Two of 8 (25.0%) microinvasive SCC patients with positive RMs were confirmed to have residual diseases (1 microinvasive SCC and 1 invasive SCC) after hysterectomy. Four out of 360 (1 positive RM, 3 negative RM) CIN cases recurred during the study period. Conclusions These results suggest that CIN patients with positive RMs after LEEP with CC may be followed up without additional treatment.
Broad Spectrum Epidemiological Contribution of Cannabis and Other Substances to the Teratological Profile of Northern New South Wales: Geospatial and Causal Inference Analysis&nbsp;
Authors: Reece Albert Stuart , Hulse Gary Kenneth 
Published: September 2020

Abstract
Background. Whilst cannabis commercialization is occurring rapidly guided by highly individualistic public narratives, evidence that all congenital anomalies (CA) increase alongside cannabis use in Canada, a link with 21 CA’s in Hawaii, and rising CA’s in Colorado indicate that transgenerational effects can be significant and impact public health. It was therefore important to study Northern New South Wales (NNSW) where cannabis use is high.Methods. Design: Cohort. 2008-2015. Setting: NNSW and Queensland (QLD), Australia. Participants. Whole populations. Exposures. Tobacco, alcohol, cannabis. Source: National Drug Strategy Household Surveys 2010, 2013. Main Outcomes. CA Rates. NNSW-QLD comparisons. Geospatial and causal regression. Results. Cardiovascular, respiratory and gastrointestinal anomalies rose with falling tobacco and alcohol but rising cannabis use rates across Queensland. Maternal age NNSW-QLD was not different (2008-2015: 4265/22084 v. 96473/490514 >35 years/total, Chi.Sq.=1.687, P=0.194). A higher rate of NNSW cannabis-related than cannabis-unrelated defects occurred (prevalence ratio (PR)=2.13, 95%C.I. 1.80-2.52, P=3.24x10-19). CA’s rose more potently with rising cannabis than with rising tobacco or alcohol use. Exomphalos and gastroschisis had the highest NNSW:QLD PR (6.29(2.94-13.48) and 5.85(3.54-9.67)) and attributable fraction in the exposed (84.11%(65.95-92.58%) and 82.91%(71.75-89.66%), P=2.83x10-8 and P=5.62x10-15). In multivariable geospatial models cannabis was significantly linked with cardiovascular (atrial septal defect, ventricular septal defect, tetralogy of Fallot, patent ductus arteriosus), genetic (chromosomal defects, Downs syndrome), gastrointestinal (small intestinal atresia), body wall (gastroschisis, diaphragmatic hernia) and other (hypospadias) (AVTPCDSGDH) CA’s. In linear modelling cannabis use was significantly linked with anal stenosis, congenital hydrocephalus and Turner syndrome (ACT) and was significantly linked in borderline significant models (model P<0.1) with microtia, microphthalmia, and transposition of the great vessels. At robust and mixed effects inverse probability weighted multivariable regression cannabis was related to 18 defects. 16/17 E-Values in spatial models were >1.25 ranging up to 5.2x1013 making uncontrolled confounding unlikely.Conclusions. These results suggest that population level CA’s react more strongly to small rises in cannabis use than tobacco or alcohol; cardiovascular, chromosomal, body wall and gastrointestinal CA’s rise significantly with small increases in cannabis use; that cannabis is a bivariate correlate of AVTPCDSGDH and ACT anomalies, is robust to adjustment for other substances; and is causal.
Liver Resection for Colorectal Liver-limited Metastases in Elderly Patients: A Propensity Score Matching Analysis
Authors: Jin Ke-Min , Wang Kun , Bao Quan , Wang Hong-Wei , Xing Bao-Cai 
Published: September 2020

Abstract
Background: Few studies have focused on the role of hepatectomy for colorectal liver-limited metastases in elderly patients compared to matched younger patients. Methods: From January 2000 to December 2018, 724 patients underwent hepatectomy for colorectal liver-limited metastases. Based on a 1:2 propensity score matching (PSM) model, 64 elderly patients (≥70 years of age) were matched to 128 younger patients (＜70 years of age) to obtain two balanced groups with regards to demographic, therapeutic and prognostic factors.Results: There were 73 elderly and 651 younger patients in the unmatched cohort. Compared with the younger group (YG), the elderly group (EG) had significantly higher proportion of American Society of Anesthesiologists score Ⅲ and comorbidities, and lower proportion of more than 3 liver metastases and postoperative chemotherapy (p<0.05). After PSM for these factors, rat sarcoma virus proto-oncogene/B-Raf proto-oncogene (RAS/BRAF) mutation status and primary tumor sidedness, the EG had significantly less median intraoperative blood loss than the YG (175ml vs. 200ml, p=0.046), a shorter median postoperative hospital stay (8 days vs. 11 days, p=0.020) and a higher readmission rate (4.7% vs.0%, p=0.036). The EG also had longer disease-free survival (DFS), overall survival (OS) and cancer-specific survival (CSS) compared to the YG, but these findings were not statistically significant (p>0.05). Old age was not an independent factor for DFS, OS and CSS by Cox multivariate regression analysis (p>0.05). Conclusions: Hepatectomy is safe for colorectal liver-limited metastases in elderly patients, and these patients may subsequently benefit from prolonged DFS, OS and CSS.
High Triglyceride-Glucose Index is Associated with Poor Cardiovascular Outcomes in Non-Diabetic ACS Patients with LDL-C Below 1.8mmol/L
Authors: Zhang Yue , Ding Xiaosong , Hua Bing , Liu Qingbo , Gao Hui , Chen Hui , Zhao Xue-Qiao , Li Weiping , Li Hongwei 
Published: September 2020

Abstract
Background: To evaluate the prognostic value of triglyceride glucose (TyG) index in non-diabetic acute coronary syndrome (ACS) patients with low-density lipoprotein cholesterol (LDL-C) below 1.8mmol/L.Methods: A total of 1655 non-diabetic ACS patients with LDL-C below 1.8mmol/L were included in the analysis. Patients were stratified into 2 groups. Incidence of acute myocardial infarction (AMI), infarct size in patients with AMI, and major adverse cardiac and cerebral event (MACCE) during a median of 35.6-month follow-up were determined and compared between the 2 groups. The TyG index was calculated using the following formula: ln [fasting triglycerides (mg/dL) ×fasting plasma glucose (mg/dL)/2].Results: Compared with the TyG index <8.33 group, the TyG index ≥8.33 group had significantly higher incidence of AMI (21.2% vs. 15.2%, p =0.014) and larger infarct size in patients with AMI (pTNI: 10.4 vs. 4.8 ng/ml, p =0.003; pCKMB: 52.8 vs. 22.0 ng/ml, p =0.006; pMyo: 73.7 vs. 46.0 ng/ml, p =0.038). Although there was no significant difference in mortality between the 2 groups, the incidence of revascularization of TyG index ≥8.33 group was significantly higher than that of TyG index <8.33 group (8.9% vs. 5.0%, p =0.035). Multivariable Cox regression revealed that the TyG index was positively associated with revascularization [HR (95% CI): 1.67 (1.02,2.75), p=0.043].Conclusion: In non-diabetic ACS patients with LDL-C below 1.8mmol/L, the high TyG index level was associated with higher incidence of AMI, larger infarct size, and higher incidence of revascularization. The high TyG index level might be a valid predictor of subsequent revascularization.Trial registration: retrospectively registered.
A Methylation-based nomogram for predicting survival in patients with lung adenocarcinoma
Authors: Wang Xuelong , Zhou Bin , Xia Yuxin , Zuo Jianxin , Liu Yanchao , Bi Xin , Luo Xiong , Zhang Chengwei 
Published: September 2020

Abstract
Background
DNA methylation alteration is frequently observed in Lung adenocarcinoma (LUAD) and may play important roles in carcinogenesis, diagnosis, and prognosis. Thus, this study aimed to construct a reliable methylation-based nomogram, guiding prognostic classification screening and personalized medicine for LUAD patients.
Method:
The DNA methylation data, gene expression data and corresponding clinical information of lung adenocarcinoma samples were extracted from The Cancer Genome Atlas (TCGA) database. Differentially methylated sites (DMSs) and differentially expressed genes (DEGs) were obtained and then calculated expression correlation by pearson correlation coefficient. Functional enrichment analysis and Protein-protein interaction network were used to explore the biological roles of aberrant methylation genes. A prognostic risk score model was constructed using univariate Cox and LASSO analysis and was assessed in an independent cohort. A methylation-based nomogram that included the risk score and the clinical risk factors was developed, which was evaluated by concordance index and calibration curves.
Result
We identified a total of 1362 DMSs corresponding to 471 DEGs with significant negative correlation, including 752 hypermethylation sites and 610 hypomethylation sites. Univariate cox regression analysis showed that 59 DMSs were significantly associated with overall survival. Using LASSO method, we constructed a three-DMSs signature that was independent predictive of prognosis in the training cohort. Patients in high-risk group had a significant shorter overall survival than patients in low-risk group classified by three-DMSs signature (log-rank p = 1.9E-04). Multivariate cox regression analysis proved that the three-DMSs signature was an independent prognostic factor for LUAD in TCGA-LUAD cohort (HR = 2.29, 95%CI: 1.47–3.57, P = 2.36E-04) and GSE56044 cohort (HR = 2.16, 95%CI: 1.19–3.91, P = 0.011). Furthermore, a nomogram, combining the risk score with clinical risk factors, was developed with C-indexes of 0.71 and 0.70 in TCGA-LUAD and GSE56044 respectively.
Conclusions
The present study established a robust three-DMSs signature for the prediction of overall survival and further developed a nomogram that could be a clinically available guide for personalized treatment of LUAD patients.
A potent synthetic nanobody targets RBD and protects mice from SARS-CoV-2 infection
Authors: Li Dianfan , Li Tingting , Cai Hongmin , Yao Hebang , Zhou Bingjie , Zhang Ning , Gong Yuhuan , Zhao Yapei , Shen Quan , Qin Wenming , Hutter Cedric , Lai Yanling , Kuo Shu-Ming , Bao Juan , Lan Jiaming , Seeger Markus , Wong Gary , Bi Yuhai , LAVILLETTE Dimitri 
Published: September 2020

Abstract
SARS-CoV-2, the causative agent of COVID-191, recognizes host cells by attaching its receptor-binding domain (RBD) to the host receptor ACE22-7. Neutralizing antibodies that block RBD-ACE2 interaction have been a major focus for therapeutic development8-18. Llama-derived single-domain antibodies (nanobodies, ~15 kDa) offer advantages including ease of production and possibility for direct delivery to the lungs by nebulization19, which are attractive features for bio-drugs against the global respiratory disease. Here, we generated 99 synthetic nanobodies (sybodies) by in vitro selection using three libraries. The best sybody, MR3 bound to RBD with high affinity (KD = 1.0 nM) and showed high neutralization activity against SARS-CoV-2 pseudoviruses (IC50 = 0.40 μg mL-1). Structural, biochemical, and biological characterization of sybodies suggest a common neutralizing mechanism, in which the RBD-ACE2 interaction is competitively inhibited by sybodies. Various forms of sybodies with improved potency were generated by structure-based design, biparatopic construction, and divalent engineering. Among these, a divalent MR3 conjugated with the albumin-binding domain for prolonged half-life displayed highest potency (IC50 = 12 ng mL-1) and protected mice from live SARS-CoV-2 challenge. Our results pave the way to the development of therapeutic nanobodies against COVID-19 and present a strategy for rapid responses for future outbreaks.
Massive Hemothorax in A Pregnant Patient With Neurofibromatosis Type 1
Authors: Hashimoto Kumiko , Nomata Yuji , Fukui Takayuki , Takada Akira , Narita Kunio 
Published: September 2020

Abstract
Background: Spontaneous hemothorax in a patient with neurofibromatosis type 1 is a less common though lethal complication, and there is no report which occurred in the pregnant period. We here present the first case of hemothorax in a neurofibromatosis type 1 patient during pregnancy and discus on the difficulty in diagnosis and treatment choice.Case Presentation: A 39-year-old female at 34 weeks gestation presented with sudden left back pain and dyspnea. Chest radiography revealed massive left pleural effusion. Although the patient was hemodynamically stable, the fetus was in a critical condition. Emergency cesarean section and endovascular coil embolization of the aneurysm of the intercostal artery were performed successfully. The patient’s condition improved immediately, and she was discharged 1 month later. Conclusions: A neurofibromatosis type 1 patients have the potential to develop massive hemothorax without gross lesions, especially late in pregnancy and postpartum.
Exploring the Acceptability and Relevance of Tool-supported Advance Care Planning (ACP) for a Long-term Care (LTC) Home Environment
Authors: Sussman Tamara , Kaasalainen Sharon , Bimman Rennie , Punia Harveer , Edsell Nathaniel , Sussman Jess 
Published: September 2020

Abstract
Objectives: Despite known benefits, advance care planning (ACP) is rarely a component of usual practice in long-term care (LTC). A series of tools and workbooks have been developed to support ACP uptake. Yet, their acceptability and relevance for LTC has yet to be examined. This study explored the extent to which available ACP materials hold promise in improving ACP engagement in LTC by (1) exploring LTC home staff’s reactions to tool supported ACP and (2) examining if available ACP tools include content of relevance to LTC. Methods: A combination of focus group deliberations with LTC home staff (N=32) and content analysis of publicly available ACP workbooks (N=32) were used to meet the study aims. Results: Focus group deliberations suggested that tool-directed ACP is a promising approach for LTC, provided tools include psychosocial elements and are paper-based. Content analysis of available tools revealed that only a handful of paper-based ACP tools (32/611, 5%) include, psychosocial content, with most encouraging psychosocially-oriented reflections (30/32, 84%), and far fewer providing direction around other elements of ACP such as communicating psychosocial preferences (14/32, 44%) or transforming preferences into a documented plan (7/32, 22%).Conclusions: Tool-supported ACP appears acceptable to LTC staff. To improve ACP uptake in LTC selected tools should include psychosocial content that can be supported by a range of clinical and non-clinical staff. Available ACP tools may require infusion of scenarios pertinent to frail older persons, and a better balance between psychosocial content that elicits reflections and psychosocial content that supports communication.
MIB1 Upregulates IQGAP1 and Promotes Pancreatic Cancer Progression by inducing ST7 Degradation
Authors: Liu Tao , Zhang Bin , jin xin , Cheng Xiang 
Published: September 2020

Abstract
BackgroundPancreatic cancer is a highly heterogeneous and has a poor prognosis. Elucidating the molecular mechanisms underlying pancreatic cancer progression is essential for improving patient survival. Although the E3 ubiquitin ligase mind bomb 1 (MIB1) is involved in cancer cell proliferation and is often overexpressed in pancreatic cancer, the role of MIB1 in pancreatic cancer progression remains unclear.Methods The relationship of MIB1 with the clinicopathological features of pancreatic tumors was bioinformatically investigated in different datasets. The protein levels of MIB1 and ST7 were assessed by Western blotting and immunohistochemistry. The role of MIB1 and ST7 in pancreatic cancer growth was assessed by MTS assays, colony formation assays, and experiments in mouse xenograft models. The interaction between MIB1 and ST7 was investigated by co-immunoprecipitation. The relationship between MIB1, ST7, and IQGAP1 levels was explored by Western blotting and quantitative real-time PCR.ResultsMIB1 expression was elevated in pancreatic cancer tissues, and its expression levels were associated with unfavorable prognosis. MIB1 overexpression enhanced pancreatic cancer proliferation and invasion in vitro and in vivo. We identified ST7 as a novel MIB1 target for proteasomal degradation. Further, we found that ST7 suppressed tumor growth by downregulating IQGAP1 in pancreatic cancer cells.ConclusionsThese data suggest that MIB1 promotes pancreatic cancer progression by inducing ST7 degradation. ST7 suppresses tumor growth by downregulating IQGAP1 in pancreatic cancer cells. Therefore, the MIB1/ST7/IQGAP1 axis is essential for pancreatic cancer progression, and MIB1 inhibition may improve the survival of pancreatic cancer patients.
The ‘Un-Shrunk’ Partial Correlation in Gaussian Graphical Models
Authors: Bernal Victor , Bischoff Rainer , Horvatovich Peter , Guryev Victor , Grzegorczyk Marco 
Published: September 2020

Abstract
Background: In systems biology, it is important to reconstruct regulatory networks from quantitative molecular profiles. Gaussian graphical models (GGMs) are one of the most popular methods to this end. A GGM consists of nodes (representing the transcripts, metabolites or proteins) inter-connected by edges (reflecting their partial correlations). Learning the edges from quantitative molecular profiles is statistically challenging, as there are usually fewer samples than nodes (‘high dimensional problem’). Shrinkage methods address this issue by learning a regularized GGM. However, it is an open question how the shrinkage affects the final result and its interpretation.Results: We show that the shrinkage biases the partial correlation in a non-linear way. This bias does not only change the magnitudes of the partial correlations but also affects their order. Furthermore, it makes networks obtained from different experiments incomparable and hinders their biological interpretation. We propose a method, referred to as the ‘un-shrunk’ partial correlation, which corrects for this non-linear bias. Unlike traditional methods, which use a fixed shrinkage value, the new approach provides partial correlations that are closer to the actual (population) values and that are easier to interpret. We apply the ‘un-shrunk’ method to two gene expression datasets from Escherichia coli and Mus musculus.Conclusions: GGMs are popular undirected graphical models based on partial correlations. The application of GGMs to reconstruct regulatory networks is commonly performed using shrinkage to overcome the “high-dimensional” problem. Besides it advantages, we have identified that the shrinkage introduces a non-linear bias in the partial correlations. Ignoring this type of effects caused by the shrinkage can obscure the interpretation of the network, and impede the validation of earlier reported results.
In Silico Mutagenesis Based Remodeling of SARs-CoV-1 Peptide (ATLQAIAS) to Inhibit SARs-CoV-2: Structural-dynamics and Free Energy Calculations
Authors: Khan Abbas , Umbreen Shaheena , Hameed Asma , Fatima Rida , Zahoor Ujala , Babar Zainib , Waseem Muhammad , Hussain Zahid , Rizwan Muhammad , Zaman Nasib , Ali Shahid , Suleman Muhammad , Shah Abdullah , Ali Liaqat , Ali Syed Shujait , Wei Dong-Qing 
Published: September 2020

Abstract
Background:The prolific spread of COVID-19 caused by a novel coronavirus (SARS-CoV-2) from its epicenter in Wuhan, China, to every nook and cranny of the world after December 2019, jeopardize the prevailing health system in the world and has raised serious concerns about human safety. To date efforts are continuing to design small molecule inhibitor, vaccines and many other therapeutic options are practiced but their final therapeutic potential is still to be tested. Using the old drug or vaccine or peptides could aid this process to avoid such long experimental procedure. Results:Hence, here we have repurposed a small peptide (ATLQAIAS) from the previous study which reported the inhibitory effects of this peptide. We used in silico mutagenesis approach to design more peptides from the native wild peptide, which revealed that substitutions (T2W, T2Y, L3R and A5W) could increase the binding affinity of the peptide towards the 3CLpro. Furthermore, using MD simulation and free energy calculation confirmed its dynamics stability and stronger binding affinities. Per-residues energy decomposition analysis revealed that the specified substitution significantly increased the binding affinity at residue level. Conclusion:Our wide-ranging analyses of binding affinities disclosed that our designed peptide owns the potential to hinder the SARS-CoV-2 and will reduce the progression of SARs-CoV-2-borne pneumonia. Our analysis strongly suggests the experimental and clinical validation of these peptides to curtail the recent corona outbreak.