bluuebunny/crossref_metadata_2025_split huggingface dataset:
Virtual Screening of DPP-4 Inhibitors Using QSAR-Based Artificial Intelligence and Molecular Docking of Hit Compounds to DPP-8 and DPP-9 Enzymes
Authors: Hermansyah Oky , Bustamam Alhadi , Yanuar Arry 
Published: January 2020

Abstract
Background: Dipeptidyl Peptidase-4 (DPP-4) inhibitors are becoming an essential drug in the treatment of type 2 diabetes mellitus, but some classes of these drugs have side effects such as joint pain that can become severe to pancreatitis. It is thought that these side effects appear related to their inhibition against enzymes DPP-8 and DPP-9. Objective: This study aims to find DPP-4 inhibitor hit compounds that are selective against the DPP-8 and DPP-9 enzymes. By building a virtual screening workflow using the Quantitative Structure-Activity Relationship (QSAR) method based on artificial intelligence (AI), millions of molecules from the database can be screened for the DPP-4 enzyme target with a faster time compared to other screening methods. Result: Five regression machine learning algorithms and four classification machine learning algorithms were used to build virtual screening workflows. The algorithm that qualifies for the regression QSAR model was Support Vector regression with R 2 pred 0.78, while the classification QSAR model was Random Forest with 92.21% accuracy. The virtual screening results of more than 10 million molecules from the database, obtained 2,716 hit compounds with pIC50 above 7.5. Molecular docking results of several potential hit compounds to the DPP-4, DPP-8 and DPP-9 enzymes, obtained CH0002 hit compound that has a high inhibitory potential against the DPP-4 enzyme and low inhibition of the DPP-8 and DPP-9 enzymes. Conclusion: This research was able to produce DPP-4 inhibitor hit compounds that are potential to DPP-4 and selective to DPP-8 and DPP-9 enzymes so that they can be further developed in the DPP-4 inhibitors discovery. The resulting virtual screening workflow can be applied to the discovery of hit compounds on other targets. Keywords: Artificial Intelligence; DPP-4; KNIME; Machine Learning; QSAR; Virtual Screening
Small Intestinal Bacterial Overgrowth and Orocecal Transit Time in Patients of Nonalcoholic Fatty Liver Disease
Authors: Shi Haitao , Mao Lijuan , Wang Lianli , Quan Xiaojing , Xu Xiaoyu , Cheng Yan , Zhu Shanshan , Dai Fei 
Published: January 2020

Abstract
Background: To explore the frequency of small intestinal bacterial overgrowth (SIBO) and orocecal transit time (OCTT) in patients with nonalcoholic fatty liver disease (NAFLD). Methods: 103 patients with NAFLD and 49 healthy controls were enrolled. Clinical indicators such as body mass index (BMI), liver function, blood lipids, HOMA-IR, serum endotoxin of NAFLD patients were collected and examined. Fibro Touch was used to detect the (controlled attenuation parameter) CAP and liver stiffness measurement (LSM). SIBO and OCTT were measured by lactulose hydrogen breath test. Results: The incidence of SIBO in NAFLD patients (58.3%) was significantly higher than that in healthy controls (26.5%). The level of serum endotoxin in NAFLD patients was higher than that in healthy controls. The levels of CAP, LSM, serum endotoxin, ALT, AST and HOMA-IR in SBIO-positive NAFLD patients were higher than those in SIBO-negative patients. There was no significant difference in GGT, TG, LDL and BMI between the two groups. OCTT in NAFLD patients was longer than that in healthy controls. It was also observed that OCTT in SIBO-positive NAFLD patients was significantly delayed compared with SIBO-negative NAFLD patients. Conclusions: Patients with NAFLD exhibit the increased incidence rate of SIBO and prolonged OCTT; SIBO in NAFLD patients is a contributing factor to the elevated transaminase, hepatic steatosis, progression of liver fibrosis and prolonged OCTT.
Synthesis and biological evaluation of heterocyclic 1,2,4-Triazole scaffolds as promising pharmacological agents
Authors: Kumari Mukesh , Tahlan Sumit , Narasimhan Balasubramanian , Ramasamy Kalavathy , Lim Siong Meng , Shah Syed Adnan Ali , Mani Vasudevan , Kakkar Saloni 
Published: January 2020

Abstract
Background: Triazole is an important heterocyclic moiety that occupied a unique position in heterocyclic chemistry, due to its large number of biological activities. It exists in two isomeric forms i.e. 1,2,4-triazole and 1,2,3-triazole and used as core molecule for the design and synthesis of many medicinal compounds. 1,2,4-Triazole possess broad spectrum of therapeutically interesting drug candidates such as analgesic, antiseptic, antimicrobial, antioxidant, antiurease , anti-inflammatory, diuretics, anticancer, anticonvulsant, antidiabetic, antimigrain agents.Methods: The structure of all synthesized compounds were characterized by physicochemical properties and spectral means (IR and NMR). The synthesized compounds were evaluated for their in vitro antimicrobial activity against Gram-positive (B. subtilis), Gram-negative (P. aeruginosa and E. coli) bacterial and fungal (C. albicans and A. niger) strains by tube dilution method using ciprofloxacin, amoxicillin and fluconazole as standards. In-vitro antioxidant and anti-urease screening was done by DPPH assay and indophenol method, respectively. The in-vitro anticancer evaluation was carried out against MCF-7 and HCT116 cancer cell lines using 5-FU and cisplatin as standards.Results, discussion and conclusion: The biological screening results reveal that the compounds T5 (MICBS, EC = 24.7µM, MICPA, CA = 12.3 µM) and T17 (MICAN = 27.1µM) exhibited potent antimicrobial activity as comparable to standards ciprofloxacin, amoxicillin (MICCipro = 18.1µM, MICAmo = 17.1µM) and fluconazole (MICFlu = 20.4µM), respectively. The antioxidant evaluation showed that compounds T2 (IC50 = 34.83 µg/ml) and T3 (IC50 = 34.38 µg/ml) showed significant antioxidant activity and comparable to ascorbic acid (IC50 = 35.44 µg/ml). Compounds T3 (IC50 = 54.01µg/ml) was the most potent urease inhibitor amongst the synthesized compounds and compared to standard thiourea (IC50 = 54.25 µg/ml). The most potent anticancer activity showed by compounds T2 (IC50 = 3.84 μM) and T7 (IC50 = 3.25 μM) against HCT 116 cell lines as compared to standard 5-FU (IC50 = 25.36 μM).
Isolation, Characterization, Structural Elucidation and Anti-Bacterial Activities of Roots Extracts of Cucumis Ficifolius
Authors: Nigussie Gashaw , Ashenef Sintayehu 
Published: January 2020

Abstract
Cucumis ficifolius (family Cucurbitaceae) is traditionally used for the treatment of diarrhea, teeth-ach, wound, burns, bleeding from external cuts and against different infectious diseases. With the absence of previous scientific report on the roots of the plant, this study was focused on isolation of chemical constituents and evaluation of their anti-bacterial activities of the roots of C. ficifolius. The n-hexane, ethyl acetate and methanol extracts of the roots of C. ficifolius were investigated for their phytochemical constituents and the results revealed that C. ficifolius is rich in many secondary metabolites such as saponins, terpenoids, glycosides, and steroids. But tannins and alkaloids were not observed. The ethyl acetate extract was subjected to column chromatography over silica gel and furnished three compounds namely compound-1, compound- 2 and compound-3. The structures of these compounds were characterized using FTIR, 1H-NMR, 13C-NMR and DEPT-135. The crude extracts and the isolated compounds were tested against four bacteria strains (Gram negative, E. coli and p. aeruginosa; Gram positive, S. aureus and B. subtilis) using Agar well diffusion method, the results showed that the methanol extracts and compound-2 were active against all the tested bacteria. Accordingly, 12.34, 18.25 and 23.75 mm zone of inhibition against B. subtilis were found at the concentration of 20, 30 and 40 μg/mL MeOH extract respectively. Similarly 9.5, 13.25 and 17.25 mm zone of inhibition were found for the same bacteria strains and concentrations of compound-2. These results showed the increase of inhibition zone with concentration. However, the n-hexane crude extract was found not to have anti-bacterial activity towards the tested bacteria strains.
Histone deacetylase inhibitors Induce Expression of Chromosomally Tagged Variant-Specific Surface Protein Genes in Giardia lamblia
Authors: Orozco Daniel Roberto , Garlapati Srinivas 
Published: January 2020

Abstract
ObjectiveEpigenetic mechanisms involving histone acetylations have been proposed to explain the process of antigenic variation in Giardia lamblia. However, due to limited availability of specific antibodies for all the vsp variants present in the genome, it was difficult to monitor vsp gene switching. In this study, we have used endogenous tagging method to tag specific vsp genes vsp1267 and vsp9B10A with a sequence encoding hemagglutinin (HA) epitope at the 3’end of the coding sequences without altering the 5’ upstream elements. With this method we have monitored the expression of the tagged vsp genes in cells treated with histone deacetylase inhibitors using RT-PCR. ResultsOur results show that vsp1267-3XHA can be induced by treatment with sodium 4-phenylbutyrate, M344 and splitomicin but not by apicidin and Trichostatin A, while vsp9B10A-3XHA expression can be induced by Trichostatin A and splitomicin but not by sodium 4-phenylbutyrate, M344 and apicidin. The induced expression of these variants was not due to growth inhibition. These results support the hypothesis that histone acetylations play a role in vsp gene expression.
Immunophenotyping of the PD-L1-positive cells in angioimmunoblastic T cell lymphoma and Hodgkin disease
Authors: Tiemann Markus , Samoilova Vera , Atiakshin Dmitri , Buchwalow Igor 
Published: January 2020

Abstract
Objective Programmed Death-1(PD-1) and its ligand PD-L1 are now used as predictive biomarkers to guide clinical decisions. Precise characterization of PD-L1-positive cells may contribute to our knowledge of which patients derive benefit from the PD-L1 blockade therapy. ResultsTo address this issue, we performed immunophenotyping of PD-L1-positive cells in Hodgkin lymphoma and in angioimmunoblastic T-cell lymphoma (AITL) employing multiple immunofluorescent immunolabeling. We found that PD-L1-positive cells and PD-1-positive cells both in Hodgkin lymphoma and in AITL belong to two completely different cell lineages. In both lymphomas, PD-1 was found exclusively in T-lymphocytes, whereas PD-L1 was revealed in the tumor microenvironment cells including macrophages. PD-L1 was also detected in CD30-positive cells in Hodgkin lymphoma but not in AITL. The marker of B-cell lineage, CD20, was not detectable in PD-L1-positive cells both in AITL and in Hodgkin. Our study highlights the importance of comprehensive assessment of PD-1/PD-L1 regulatory pathways for employing PD-L1 as a predictive biomarker in clinical practice. PD-L1-antibody therapy is proven in Hodgkin lymphoma. Comparative immunophenotyping of the PD-1/PD-L1 axis provides a support for attempts to prove this principle also for AITL.
The role of culture and religion on sexual and reproductive health indicators and help-seeking behaviour amongst 1.5 generation migrants in Australia: A quantitative pilot study
Authors: Dune Tinashe , Ayika David , Thepsourinthone Jack , Mapedzahama Virginia , Mengesha Zelalem , Perz Janette 
Published: January 2020

Abstract
Background: 1.5 generation migrants in Australia (those who migrate as children) often enter a new cultural and religious environment, with its own set of constructs of sexual and reproductive health (SRH), at a crucial time in their psychosexual development—puberty/adolescence. 1.5 generation migrants may thus have to contend with constructions of SRH from at least two cultures which may be at conflict on the matter. This study was designed to investigate the role of culture and religion on sexual and reproductive health indicators and help-seeking behaviour amongst 1.5 generation migrants.Methods: 111 participants completed an online survey which included questions about their cultural connectedness, religion, sexual and reproductive health and help-seeking behaviour. Kruskall-Wallis tests were used to analyse the data. Results: There was no significant difference between ethnocultural groups or levels of cultural connectedness in relation to sexual and reproductive health help-seeking behaviours. The results do suggest differences between religious groups in regards to seeking help specifically from young peoples’ parents. Notably, youth who reported having ‘no religion’ were more likely to seek help with sexual and reproductive health matters from their parent(s). Conclusions: Managing cross-cultural experiences are often noted in extant literature as a barrier to sexual and reproductive health help-seeking. However, while cultural norms of migrants’ country of origin can remain strong it is religion that seems to have more of an impact on how 1.5 generation migrants seek help for SRH issues. This suggests that while 1.5 generation migrants may need to adapt to a new ethnocultural environment little about their religious beliefs or practices may require adaptation in Australia. Given that religion can play a role in young peoples’ sexual and reproductive health religious organisations are well placed to encourage young people’s help-seeking behaviours.
Accounting for regional transmission variability and the impact of malaria control interventions in Ghana: A population level mathematical modelling approach.
Authors: Awine Timothy , Silal Sheetal P 
Published: January 2020

Abstract
Background Assessing the effectiveness of malaria control measures in Ghana will require taking transmission dynamics of the disease into account given the influence of climate variability in the region of interest. The impact of preventative interventions on malaria incidence and the prospects of meeting program timelines in Ghana have been investigated using mathematical models based on regionally diverse climatic zones. Methods An ordinary non-linear differential equation model with its associated rate parameters was developed incorporating the transitions between various disease compartments for three ecological zones in Ghana. Model parameters were estimated using data captured on the District Health Information Management System in Ghana from 2008 to 2017.The impact of insecticide treated bed nets and indoor residual spraying on the incidence of malaria were simulated at various levels of coverage and protective effectiveness in each ecological zone. To fit the model, Approximate Bayesian Computational sampling approach was adopted. Results Increasing the coverage levels of both long lasting insecticide treated bed nets or indoor residual spraying activities without a corresponding increase in their proper use or patronage does not impact highly on averting predicted incidence of malaria in Ghana. Improving on the protective efficacy of long lasting insecticide treated bed nets through proper usage could lead to substantial reductions in the predicted incidence of malaria. Similar results were obtained with indoor residual spraying across all zones. Conclusions Projected goals set in the National Strategic plan for malaria control 2014-2020 as well as WHO targets for malaria pre-elimination by 2030 are only likely be achieved if a substantial improvement in treated bed net usage is achieved coupled with targeted deployment of indoor residual spraying with high efficacy.
Alix and Syntenin-1 direct amyloid precursor protein and amyloid beta trafficking into extracellular vesicles
Authors: Cone Allaura S. , Hurwitz Stephanie N. , Lee Glorida S. , Yuan Xuegang , Zhou Yi , Li Yan , Meckes David 
Published: January 2020

Abstract
Background: Endosomal trafficking and amyloidogenic cleavage of amyloid precursor protein (APP) is believed to play a role in the neurodegeneration observed in Alzheimer’s disease (AD). Recent evidence has suggested that packaging and secretion of APP and amyloid beta into small extracellular vesicles (EVs) may facilitate uptake of these neurotoxic factors during disease progression. However, the molecular mechanisms underlying trafficking of APP into EVs are poorly understood. Results: In this study, the mechanism and impact of amyloid precursor protein (APP) trafficking into extracellular vesicles (EVs) were assessed by a series of inducible gene knockdowns. We demonstrate that vesicle-associated proteins Alix and Syntenin-1 are essential for proper subcellular localization and efficient EV secretion of APP via an endosomal sorting complexes required for transport (ESCRT)-independent pathway. The neurotoxic metabolite amyloid beta (Aβ) is similarly secreted in association with small vesicles. These mechanisms are conserved in terminally differentiated neuron-like cells. Furthermore, knockdown of Alix and Syntenin-1 alters the subcellular localization of APP, sequestering the precursor protein to endoplasmic reticulum and endolysosomal compartments, respectively. Finally, transfer of small EVs containing APP confers an increase in reactive oxygen species production and neurotoxicity to human induced pluripotent stem cell-derived cortical neurons and naïve primary neurons, an effect that is ameliorated by Alix and Syntenin-1 depletion. Conclusions: Altogether these findings elucidate a novel mechanism for understanding the intracellular trafficking of APP and Aβ into secreted extracellular vesicles, and the resultant potential impact on neurotoxicity in the context of Alzheimer’s disease amyloidopathy.
Medical exercise and physiotherapy frequency and compliance as predictors for a recurrence of chronic nonspecific low back pain
Authors: Krause Frieder , Niederer Daniel , Banzer Winfried , Vogt Lutz 
Published: January 2020

Abstract
Purpose A considerable part of nonspecific low back pain patients suffer from a recurrence of symptoms after therapy cessation. The aim of this study was to evaluate the predictive value of active and passive treatments and treatment modalities on a recurrence of back pain after cessation of medically prescribed therapy. Methods Patients with unspecific low back pain from a health- and therapy-center were included. Treatments and treatment modalities as therapy measures were monitored and categorized as active or passive measures. During the year after therapy cessation, patients were monitored to retrieve information about recurrence of symptoms. Patients were dichotomized (recurrence versus no recurrence). An ROC-Analysis was used to determine optimal cut-offs for relevant treatment characteristics’ impact on recurrence risk. The relative risk for a recurrence was calculated based on Chi 2 -test. Results Data from 96 patients (56f, 49±11 years) were analysed. A total of 34 patients had recurring back pain. The frequency of active treatment differed significantly between groups with or without recurrence. A therapy frequency of 1.45 active treatments/week was a sensitive cut-off (sensitivity: 0.73) to discriminate the recurrence groups. Participants with a therapy frequency of less than 1.45 treatments per week showed an 82% increased relative recurrence risk (RR: 1.824 (95%-CI: 1.077-3.087)). Conclusions The results empathize the importance of active treatments (i.e. exercise) in the therapy and (secondary) prevention of unspecific low back pain. Less than 1.45 active treatment sessions/week increases the 1-year-risk of a recurrence by 82%.
Assessment of the Efficacy of the Far Cortical Locking Technique for Proximal Humeral Fractures: A Comparison with the Conventional Bicortical Locking Technique
Authors: Seo Joong-bae , Yoon Sunghyun , Yi Hyung-Seok , Kim Jun-Kyom , Kim Kyu-Beom , Yoo Jae-Sung 
Published: January 2020

Abstract
Background Locking plate fixation is one of the treatment strategies for the management of proximal humeral fractures. However, stiffness after locking plate fixation is a clinical concern. The mechanical stiffness of the standard locking plate system may suppress the interfragmentary motion necessary to promote secondary bone healing by callus formation. The far cortical locking (FCL) technique was developed to address this limitation in 2005. FCL allows axial motion and promotes uniform callus formation. Our study aimed to evaluate the clinical and radiological outcomes of the FCL technique when implemented in proximal humeral fracture management. Furthermore, we compared the surgical outcomes of FCL with those of the conventional bicortical locking (BCL) screw fixation technique. Methods Forty-five consecutive patients who had undergone locking fixation for proximal humeral fractures were included in this study. A proximal humeral locking plate (PHILOS) system with BCL screw fixation was used in the first 27 cases, and the periarticular proximal humeral locking plate with FCL screw fixation was used in the final 18 consecutive cases. Functional capacity was assessed using the constant score, American Shoulder and Elbow Surgeons (ASES) score, and range of motion. Radiographic outcomes were evaluated using the Paavolainen method of measuring the neck-shaft angle (NSA). Results No significant differences in clinical outcomes (ASES score, constant score, and range of motion) were found between the two groups. The union rate at 12 weeks was significantly higher in the FCL group (94.4%) than in the BCL group (66.7%, p = 0.006). No significant differences in NSA were found between the two treatment strategies. The complication rate was not significantly different between the two groups. Conclusions When implemented in proximal humeral fractures, the FCL technique showed satisfactory clinical and radiological outcomes as compared with the conventional BCL technique. The bone union rate at 12 weeks after surgery was significantly higher in the FCL group than in the BCL group. However, no significant difference in the final bone union rate was found between the two groups.
THE PLACE OF PSYCHOMETRIC TESTING IN PILOT SELECTION
Authors: Clem Peter 
Published: January 2020

ABSTRACT

Aim
Pilot training has always been a relatively expensive undertaking. So attempts to control these costs by predicting the likelihood of success or failure is a constant that is almost as old as aviation itself. Incorporation of Psychometric testing was made to pilot selection in the years between the first and second world wars. Despite the many changes that have occurred in this area, psychometric testing continues to feature in modern systems of pilot aptitude testing. This paper reviews some of the history of psychometric testing in pilot selection.
DANGERS OF DEFIBRILLATION IN FLIGHT
Authors: Beebeejaun Adam , Roby Howard 
Published: January 2020

ABSTRACT

Aim
Defibrillation is a critical aspect of advanced life support, but the inherent risks in the procedure are increased when used during an aeromedical retrieval. The dangers of defibrillation in flight can be divided in to fire, electrical, avionic interference and physical carriage and packaging. A limited body of evidence exists concerning defibrillation in flight, in part, due to under-reporting. Changes in incident reporting, increased team based simulation training and awareness of the dangers of defibrillation should allow aeromedical teams to defibrillate patients safely and expediently.