bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Emergence of Colistin- and Imipenem-Associated Multidrug Resistance in Escherichia coli Isolates from Retail Meat
Authors: Iweriebor Benson Chuks , Egbule Olivia Sochi , Obi Larry C. 
Published: December 2022

Abstract
To determine the prevalence of Escherichia coli and their drug resistance profiles in fresh pork sold at two retail outlets (open-air market and closed retail stores) in Alice, South Africa. Retail meat samples (n = 176) collected from four shops (two from open-air markets and two from closed stores) were analyzed by conventional biochemical and PCR-based molecular confirmatory tests. The confirmed isolates were profiled for antimicrobial susceptibility to a panel of 12 commercial antibiotics: tetracycline, ampicillin, sulphamethoxazole trimethoprim, erythromycin, gentamycin, colistin sulphate, cefotaxime, chloramphenicol, norfloxacin, ciprofloxacin, cefuroxime, and imipenem. Colistin, ampicillin, and erythromycin resistance genes were profiled with the gene-specific primers. Multidrug resistance (MDR) and the association of imipenem and colistin in the MDR profile were determined. A total of 68 (39.08%) E. coli isolates were confirmed by PCR analysis. Resistance was most common to erythromycin (100%), followed by cefotaxime (95.58%), ampicillin (88.23%), cefuroxime (88.23%), trimethoprim-sulphamethoxazole (88.23%), and tetracycline (60.29%). Overall, 27/68 (39.70%) were MDR (≥ 3antibiotics classes). MDR E. coli isolates associated with imipenem resistance (50.00%) and colistin resistance (33.82%) were detected. The resistance genes were detected among the isolates though not in all the phenotypically resistant isolates. The detection of colistin resistance among MDR E. coli isolates from retail meat is troubling as the drug is a last resort antibiotic. Overall, the epidemiological implications of the findings are of public health importance.
معالجات مقترحة في الإطار القانوني لاسترداد الأموال الناتجة من الفساد "دراسة في القانون الليبي"
Authors: Amhimmid Abdulbari Almabrouk - , Negasi Mohamed Ibrahim , Al-Toumi Ali Makzoum Mohammed 
Published: December 2022

الملخص
يهدف البحث إلى دراسة النظام القانوني لاسترداد أموال الدولة الناتجة من جرائم الفساد في ليبيا من جانبى القانون المنظم والجهة المختصة، وتأتي الأهمية من الحاجة الملحة لاسترداد الأموال التي نتجت من فساد بحجم ضخم في ليبيا وفق ما أشارت تقارير محلية ودولية، إضافة إلى أهمية مرحلة الاسترداد التي تعكس مدى اهتمام المشرع والجهات المختصة بحماية الأموال العامة باستعادة تلك الأموال، الأمر الذي يشكل رادع لمن يسعى للكسب غير المشروع وتُثنيه عن هذا الفعل المجرّم.
توصل البحث إلى وجود عدد من القوانين المختصة بحماية الأموال العامة، وعدم وجود قانون موحد ينظم استرداد الأموال من جرائم الفساد، بل مجموعة نصوص قانونية مبعثرة بين عدد من القوانين التي تتضمن حماية المال العام، كذلك توصل البحث إلى أن الجهات المختصة بالاسترداد متعددة بموجب القوانين، منها جهات قضائية وجهات رقابية تابعة للسلطة التشريعية وكذلك بعض الجهات التابعة للسلطة التنفيذية، ومن هذه النتائج تم إبداء بعض الملاحظات كحلول أساسية مقترحة تهدف لإعادة صياغة قانون ينظم حماية المال العام ويفصّل آليات استرداده، ثم يعيد تشكيل جهة عليا تتبع السلطة التنفيذية تتكون من موظفين متنوعي الاختصاصات، ضبطية وقضائية ومحاسبية وقانونية، ولديهم إمكانيات لغة وخلفيات قانونية لأنظمة الدول التي تهرب إليها الأموال، حتى تواكب حاجة نظام الاسترداد متعدد المراحل والإجراءات، وتساعد هذه الجهة على تنسيق إجراء استرداد الأموال في داخل الدولة وخارجها.
الكلمات المفتاحية: استرداد، الأموال، القانون، ليبيا
Primary exploration of host–microorganism interaction and enteritis treatment with an embedded membrane microfluidic chip of the human intestinal–vascular microsystem
Authors: Zhao Wei , Yao Yuhan , Zhang Tong , Lu Huijun , Zhang Xinlian , Zhao Linlin , Chen Xi , Zhu Jinhui , Sui Guodong , Zhao Wang 
Published: December 2022

Intestinal flora plays a crucial role in the host’s intestinal health. Imbalances in the intestinal flora, when accompanied by inflammation, affect the host’s intestinal barrier function. Understanding it requires studying how living cells and tissues work in the context of living organs, but it is difficult to form the three-dimensional microstructure intestinal–vascular system by monolayer cell or co-culture cell models, and animal models are costly and slow. The use of microfluidic-based organ chips is a fast, simple, and high-throughput method that not only solves the affinity problem of animal models but the lack of microstructure problem of monolayer cells. In this study, we designed an embedded membrane chip to generate an in vitro gut-on-a-chip model. Human umbilical vein endothelial cells and Caco-2 were cultured in the upper and lower layers of the culture chambers in the microfluidic chip, respectively. The human peripheral blood mononuclear cells were infused into the capillary side at a constant rate using an external pump to simulate the in vitro immune system and the shear stress of blood in vivo. The model exhibited intestine morphology and function after only 5 days of culture, which is significantly less than the 21 days required for static culture in the Transwell® chamber. Furthermore, it was observed that drug-resistant bacteria triggered barrier function impairment and inflammation, resulting in enteritis, whereas probiotics (Lactobacillus rhamnosus GG) improved only partially. The use of Amikacin for enteritis is effective, whereas other antibiotic therapies do not work, which are consistent with clinical test results. This model may be used to explore intestinal ecology, host and intestinal flora interactions, and medication assessment.
In-silico molecular interactions among the secondary metabolites of Caulerpa spp. and colorectal cancer targets
Authors: Mert-Ozupek Nazli , Calibasi-Kocal Gizem , Olgun Nur , Basbinar Yasemin , Cavas Levent , Ellidokuz Hulya 
Published: December 2022

Caulerpa spp. secrete more than thirty different bioactive chemicals which have already been used in cancer treatment research since they play a pivotal role in cancer metabolism. Colorectal cancer is one of the most common cancer types, thus using novel and effective chemicals for colorectal cancer treatment is crucial. In the cheminformatics pipeline of this study, ADME-Tox and drug-likeness tests were performed for filtering the secondary metabolites of Caulerpa spp. The ligands which were selected from the ADME test were used for in silico molecular docking studies against the enzymes of the oxidative branch of the pentose phosphate pathway (glucose-6-phosphate dehydrogenase and 6-phosphoglutarate dehydrogenase), which is of great importance for colorectal cancer, by using AutoDock Vina. Pharmacophore modeling was carried out to align the molecules. Molecular dynamic simulations were performed for each target to validate the molecular docking studies and binding free energies were calculated. According to the ADME test results, 13 different secondary metabolites were selected as potential ligands. Molecular docking studies revealed that vina scores of caulerpin and monomethyl caulerpinate for G6PDH were found as −10.6 kcal mol-1, −10.5 kcal mol-1, respectively. Also, the vina score of caulersin for 6PGD was found as −10.7 kcal mol-1. The highest and the lowest binding free energies were calculated for monomethyl caulerpinate and caulersin, respectively. This in silico study showed that caulerpin, monomethyl caulerpinate, and caulersin could be evaluated as promising marine phytochemicals against pentose phosphate pathway enzymes and further studies are recommended to investigate the detailed activity of these secondary metabolites on these targets.
Efficient catalytic degradation of methylene blue by a novel Fe3+-TiO2@CGS three-dimensional photoelectric system
Authors: Li Jian , Wang Yufei , Guo Fanhui , Chen Juan , Wang Jinxi , Fan Xiaoyong , Li Baoning , Verma Santosh Kumar , Wei Qingbo , Yan Long , Wu Jianjun 
Published: December 2022

In this study, a novel three-dimensional photoelectric system was designed and constructed for the degradation of methylene blue (MB) via photocatalysis, electrocatalysis, and photoelectric catalysis. To this end, a Ti/RuO2-IrO2-SnO2-CeO2 electrode was prepared via a thermal oxidation coating method and used as a dimensionally-stable anode (DSA). The cathode was made of a titanium sheet with Fe3+-doped TiO2 loaded on coal gasification slag (CGS) (Fe3+-TiO2@CGS) as a photocatalyst. The factors affecting the degradation efficiency, such as the supporting electrolyte, current density, and initial pH were systematically investigated. The results revealed Fe3+-TiO2@CGS three-dimensional photoelectric system exhibiting efficient synergistic performance of photocatalysis and electrocatalysis with a synergistic factor of 1.11. Photo-generated holes (h+) were generated by light irradiation and direct anodic oxidation. Furthermore, hydroxyl radicals (HO·) radicals were induced via other pathways. Such active species showed highly-oxidizing abilities, beneficial to the degradation of methylene blue (MB). The representative Fe3+-TiO2@CGS three-dimensional photoelectric system showed super high degradation efficiency at pH 11 and current density of 18.76 mA cm−2. Using NaCl as a supporting electrolyte, the degradation yield reached 99.98% after 60 min of photoelectrical treatment. Overall, the novel Fe3+-TiO2@CGS three-dimensional photoelectrical system looks very promising for the highly efficient catalytic degradation of organic contaminants.
The effectiveness of a mobile intervention to reduce young adults’ alcohol consumption to not exceed low-risk drinking guidelines
Authors: Schulte Mieke H.J. , Boumparis Nikolaos , Kleiboer Annet , Wind Tim R. , Olff Miranda , Huizink Anja C. , Riper Heleen 
Published: December 2022

BackgroundYoung adults’ drinking habits often exceed low-risk drinking guidelines. As young adults show increased access, use, and interest in personalized content related to physical and mental well-being, mobile applications might be a suitable tool to reach this target group. This study investigates the effectiveness of “Boozebuster”, a self-guided mobile application incorporating various therapeutic principles to reduce young adults’ alcohol consumption to not exceeding low-risk drinking guideline levels, compared to an educational website condition.MethodYoung adults aged 18–30 wanting to reduce their alcohol consumption entered a two-arm, parallel-group RCT. There were no minimum drinking severity inclusion criteria. Primary outcomes included alcohol consumption quantity and frequency. Secondary outcomes included binge drinking frequency and alcohol-related problem severity. Baseline, 6-week postbaseline, and 3-month post-baseline assessments were analyzed using linear mixed model analyses. Sex, treatment adherence, experienced engagement and motivation to change alcohol use behavior were investigated as moderators. Sub-group analyses contained problem drinkers and binge drinkers.Results503 participants were randomized to the intervention or control condition. Results showed no intervention effects on primary or secondary outcomes compared to the control group. Both groups showed within-group reductions on all outcomes. Sub-group analyses in problem drinkers or binge drinkers showed similar results. Motivation to change drinking behavior and experienced engagement with the application significantly moderated the intervention effect regarding the quantity or frequency of alcohol consumption, respectively. Exploratory analyses showed that participants who indicated they wanted to change their drinking patterns during the initial PNF/MI module showed a significantly greater reduction in drinking quantity compared to those who indicated not wanting to change their drinking patterns.ConclusionThe intervention group did not show a greater reduction in alcohol-related outcomes compared to the control group, but both groups showed a similar decrease. Potential explanations include similar effectiveness of both condition due to using a minimal active control in participants predominantly in the action stage of motivation to change. Future research should further explore the effectiveness of using mobile application to reduce young adults’ drinking behavior to not exceed low-risk drinking guideline levels and identify factors that motivate participants to engage with such an intervention.
A novel necroptosis-related lncRNA based signature predicts prognosis and response to treatment in cervical cancer
Authors: Du Xinyi , Pu Xiaowen , Wang Xintao , Zhang Yuchen , Jiang Ting , Ge Yanjun , Zhu Haiyan 
Published: December 2022

Background: Necroptosis has been demonstrated to play a crucial role in the prognosis prediction and assessment of treatment outcome in cancers, including cervical cancer. The purpose of this study was to explore the potential prognostic value of necroptosis-related lncRNAs and their relationship with immune microenvironment and response to treatment in cervical cancer.Methods: Data from The Cancer Genome Atlas (TCGA) were collected to obtain synthetic data matrices. Necroptosis-related lncRNAs were identified by Pearson Correlation analysis. Univariate Cox and multivariate Cox regression analysis and Lasso regression were used to construct a necroptosis-related LncRNAs signature. Kaplan-Meier analysis, univariate and multivariate Cox regression analyses, receiver operating characteristic (ROC) curve, nomogram, and calibration curves analysis were performed to validate this signature. Gene set enrichment analyses (GSEA), immunoassays, and the half-maximal inhibitory concentration (IC50) were also analyzed.Results: Initially, 119 necroptosis-related lncRNAs were identified based on necroptosis-related genes and differentially expressed lncRNAs between normal and cervical cancer samples. Then, a prognostic risk signature consisting of five necroptosis-related lncRNAs (DDN-AS1, DLEU1, RGS5, RUSC1-AS1, TMPO-AS1) was established by Cox regression analysis, and LASSO regression techniques. Based on this signature, patients with cervical cancer were classified into a low- or high-risk group. Cox regression confirmed this signature as an independent prognostic predictor with an AUC value of 0.789 for predicting 1-year OS. A nomogram including signature, age, and TNM stage grade was then established, and showed an AUC of 0.82 for predicting 1-year OS. Moreover, GSEA analysis showed that immune-related pathways were enriched in the low-risk group; immunoassays showed that most immune cells, ESTIMAT scores and immune scores were negatively correlated with risk score and that the expression of immune checkpoint-proteins (CD27, CD48, CD200, and TNFRSF14) were higher in the low-risk group. In addition, patients in the low-risk group were more sensitive to Rucaparib, Navitoclax and Crizotinib than those in the high-risk group.Conclusion: We established a novel necroptosis-related lncRNA based signature to predict prognosis, tumor microenvironment and response to treatment in cervical cancer. Our study provides clues to tailor prognosis prediction and individualized immunization/targeted therapy strategies.
A therapeutic vaccine strategy to prevent Pneumocystis pneumonia in an immunocompromised host in a non-human primate model of HIV and Pneumocystis co-infection
Authors: Rabacal Whitney , Schweitzer Finja , Kling Heather M. , Buzzelli Lizabeth , Rayens Emily , Norris Karen A. 
Published: December 2022

IntroductionPneumocystis is a ubiquitous fungal pathogen that causes pneumonia (PCP) and pulmonary sequelae in HIV-infected individuals and other immunocompromised populations. With the success of anti-retroviral therapy for HIV-infected individuals the frequency of PCP in that population has decreased, however, PCP remains a significant cause of morbidity and mortality in individuals with hematologic and solid malignancies, and in individuals treated with immunosuppressive therapies for autoimmune diseases, and following bone marrow and solid organ transplantation. Despite the clinical need, there is no approved vaccine to prevent PCP in vulnerable populations. The ultimate goal of the field is to develop an effective vaccine that can overcome immune deficits in at risk populations and induce long-lasting protective immunity to Pneumocystis. Toward this goal, our laboratory has established a model of PCP co-infection in simian immunodeficiency virus (SIV)-infected non-human primates (NHP) and identified a recombinant protein sub-unit vaccine, KEX1, that induces robust anti-Pneumocystis immunity in immune-competent macaques that is durable and prevents PCP following simian immunodeficiency virus (SIV)-induced immunosuppression. Type I, or invariant natural killer T (iNKT) cells have the potential to provide B cell help under conditions of reduced CD4+ T cell help.MethodsIn the present study, we used the SIV model of HIV infection to address whether therapeutic vaccination with the iNKT cell-activating adjuvant α-galactosylceramide (α-GC) and KEX1 (α-GC+KEX1) can effectively boost anti-Pneumocystis humoral immunity following virus-induced immunosuppression.ResultsImmunization of antigen-experienced NHPs with α-GC+KEX1 during the early chronic phase of SIV-infection significantly boosted anti-Pneumocystis humoral immunity by increasing memory B cells and antibody titers, and enhanced titer durability during SIV-induced immunosuppression. This therapeutic vaccination strategy boosted anti-Pneumocystis immune responses during SIV-infection and contributed to protection against Pneumocystis co-infection in KEX1-vaccinated macaques.ConclusionThese studies present a novel strategy for stimulating durable anti-Pneumocystis humoral immunity in the context of complex, chronic SIV-induced immunosuppression and may be further applied to immunization of other immunosuppressed populations, and toward other common recall antigens.
Analysis identifying minimal governing parameters for clinically accurate in silico fractional flow reserve
Authors: Tanade Cyrus , Chen S. James , Leopold Jane A. , Randles Amanda 
Published: December 2022

BackgroundPersonalized hemodynamic models can accurately compute fractional flow reserve (FFR) from coronary angiograms and clinical measurements (FFRbaseline), but obtaining patient-specific data could be challenging and sometimes not feasible. Understanding which measurements need to be patient-tuned vs. patient-generalized would inform models with minimal inputs that could expedite data collection and simulation pipelines.AimsTo determine the minimum set of patient-specific inputs to compute FFR using invasive measurement of FFR (FFRinvasive) as gold standard.Materials and MethodsPersonalized coronary geometries (N=50) were derived from patient coronary angiograms. A computational fluid dynamics framework, FFRbaseline, was parameterized with patient-specific inputs: coronary geometry, stenosis geometry, mean arterial pressure, cardiac output, heart rate, hematocrit, and distal pressure location. FFRbaseline was validated against FFRinvasive and used as the baseline to elucidate the impact of uncertainty on personalized inputs through global uncertainty analysis. FFRstreamlined was created by only incorporating the most sensitive inputs and FFRsemi-streamlined additionally included patient-specific distal location.ResultsFFRbaseline was validated against FFRinvasive via correlation (r=0.714, p<0.001), agreement (mean difference: 0.01±0.09), and diagnostic performance (sensitivity: 89.5%, specificity: 93.6%, PPV: 89.5%, NPV: 93.6%, AUC: 0.95). FFRsemi-streamlined provided identical diagnostic performance with FFRbaseline. Compared to FFRbaseline vs. FFRinvasive, FFRstreamlined vs. FFRinvasive had decreased correlation (r=0.64, p<0.001), improved agreement (mean difference: 0.01±0.08), and comparable diagnostic performance (sensitivity: 79.0%, specificity: 90.3%, PPV: 83.3%, NPV: 87.5%, AUC: 0.90).ConclusionStreamlined models could match the diagnostic performance of the baseline with a full gamut of patient-specific measurements. Capturing coronary hemodynamics depended most on accurate geometry reconstruction and cardiac output measurement.
Effects of homocysteine on nonalcoholic fatty liver related disease: A mendelian randomization study
Authors: Chen Pengcheng , Yang Ze , Guo Lingyun , Huang Yingfei , Li Jingjia , Chen Xin 
Published: December 2022

Background: Since the association of homocysteine and clinical results of observational studies are controversial on non-alcoholic fatty liver related disease, we compute the two-sample Mendelian Randomization (MR) study.Objective: To evaluate whether the plasma level of homocysteine has an effect on the risk of Non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), and Cirrhosis after its progress, we investigated the causal relationships between plasma homocysteine and the three non-alcoholic fatty liver related diseases mentioned above.Design and methods: Summary estimates were elicited from the inverse-variance weighted (IVW) method through 12 single nucleotide polymorphisms (SNPs) which related to the plasma homocysteine, the SNPs were obtained from a large genome-wide association studies (GWAS) of 44,147 European participants. And the summary statistics for the latest and largest GWAS datasets for NAFLD (307576 in total and 1,578 cases), NASH (309055 in total and 99 cases) and Cirrhosis (306145 in total and 826 cases) were collected from Ristey FinnGen website where the association of genetic variations with blood metabolite levels was conducted using comprehensive metabolite profiling. The study was performed through two-sample MR method.Results: The result indicated that the plasma homocysteine is not significantly associated with NAFLD, and its progression, NASH and Cirrhosis.Conclusion: The evidence in this study is quite deficient to support the causal association of the individual plasma homocysteine with NAFLD, NASH and Cirrhosis, the putative of associations is not exist.