Miracle-dz/UniFAR-FTUs huggingface dataset:
Genetic Variations in Prostaglandin E2 Pathway Identified as Susceptibility Biomarkers for Gastric Cancer in an Intermediate Risk European Country

The cyclooxygenase-2 (COX-2)/prostaglandin E2 (PGE2) pathway exerts deleterious pleiotropic effects in inflammation-induced gastric carcinogenesis. We aimed to assess the association of genetic variants in prostaglandin-endoperoxide synthase 2 (PTGS2), ATP binding cassette subfamily C member 4 (ABCC4), hydroxyprostaglandin dehydrogenase 15-(NAD) (HPGD), and solute carrier organic anion transporter family member 2A1 (SLCO2A1) PGE2 pathway-related genes with gastric cancer (GC) risk in a European Caucasian population. A hospital-based case-control study gathering 260 GC cases and 476 cancer-free controls was implemented. Using a tagSNP approach, 51 single nucleotide polymorphisms (SNPs) were genotyped through MassARRAY® iPLEX Gold Technology or allelic discrimination by real-time polymerase chain reaction (PCR). Homozygous carriers of the minor allele for both rs689466 and rs10935090 SNPs were associated with a 2.98 and 4.30-fold increased risk for GC, respectively (95% confidence interval (CI): 1.14–7.74, p = 0.027; 95% CI: 1.22–15.16, p = 0.026), with the latter also being associated with an anticipated diagnosis age. A multifactor dimensionality reduction analysis identified an overall three-factor best interactive model composed of age, rs689466, and rs1678374 that was associated with a 17.6-fold GC increased risk (95% CI: 11.67–26.48, p < 0.0001, (cross-validation) CV consistency of 8/10 and accuracy of 0.807). In this preliminary study, several tagSNPs in PGE2 pathway-related genes were identified as risk biomarkers for GC development. This approach may help to identify higher-risk individuals and may contribute to the tailoring screening of GC in intermediate-risk European countries.
Risk Factors and Wellness Measures Associated with Prediabetes and Newly Diagnosed Type 2 Diabetes Mellitus in Hispanic Adults.

Background: To characterize the associations of clinical risk factors, lifestyle factors, and wellness measures with prediabetes and new type 2 diabetes mellitus (T2DM) diagnosis in Hispanic adults and guide primary prevention. Methods: Sangre Por Salud Biobank enrolled 3733 Hispanic adults from Phoenix, AZ, United States, from 2013 to 2018. This analysis included participants with euglycemia, prediabetes, or new T2DM diagnosis (i.e., no prior T2DM diagnosis) at enrollment. Participants completed a baseline questionnaire on cardiometabolic risk factors and wellness measures and provided biometric measurements. The associations of factors and measures with odds (95% confidence interval) of prediabetes and new T2DM diagnosis were analyzed in logistic regression models. Results: Among 3299 participants with euglycemia (n = 1301), prediabetes (n = 1718), and new T2DM diagnosis (n = 280) at enrollment, 72% were women (n = 2376/3299). In adjusted models, most cardiometabolic risk factors were positively associated with prediabetes and new T2DM diagnosis, with stronger associations for new T2DM diagnosis. Obesity (body mass index ≥30 kg/m2 vs. lower) was associated with higher odds of new T2DM diagnosis (3.14 [2.30-4.28]; P < 0.01) than prediabetes versus euglycemia (1.96 [1.66-2.32]; P < 0.01) and Interaction (P = 0.01). Similarly, waist circumference, family history of diabetes, and average systolic and diastolic blood pressure were associated with higher odds of new T2DM diagnosis versus euglycemia than prediabetes versus euglycemia. Using stepwise logistic regression modeling, a parsimonious model of age, family history of diabetes, waist circumference, diastolic blood pressure, passive tobacco exposure, and self-rated general health were associated with new T2DM diagnosis versus euglycemia. Conclusions: In Hispanic adults, modifiable cardiometabolic and lifestyle factors were associated with prediabetes and new T2DM diagnosis. Personalized interventions targeting these factors and measures could guide T2DM primary prevention efforts among Hispanic adults.
Treatment outcomes, antibiotic use and its resistance pattern among neonatal sepsis patients attending Bahawal Victoria Hospital, Pakistan

Background Sepsis is one of the major causes of neonatal mortality in Pakistan. This study aimed to investigate the treatment outcomes, antibiotic use and its resistance pattern among neonatal sepsis patients attending a tertiary care hospital in Pakistan. We also aimed to identify the factors affecting mortality in neonatal sepsis patients. Methods A descriptive, cross-sectional study was conducted in the pediatric wards of the Bahawal Victoria Hospital, Bahawalpur, Pakistan. All eligible neonatal sepsis patients who were registered at the study site from January 1, 2019 to June 30, 2019 were included in the study. The data collection form included information on patient’s characteristics, antibiotic use and its sensitivity pattern, laboratory and microbiological data, and final treatment outcomes. Treatment outcomes included, discharged (with treatment success), leave against medical advice (LAMA), discharged on request (DOR) and death. Multivariable binary logistic regression analysis was used to find the independent factors associated with death. A p-value of less than 0.05 was considered statistically significant. Results Among the total 586 patients, 398 (67.9%) were male, 328 (56%) were preterm, 415 (70.8%) were diagnosed with early onset sepsis, 299 (51%) were born with low birth weight. Most of the patients (n = 484, 82.6%) were treated with amikacin+cefotaxime at the start of treatment. Culture was positive in 52 (8.9%) patients and the most commonly identified bacteria included, Klebsiella species (n = 19, 36.5%) followed by E. coli (n = 15, 28.5%) and Staphylococcus aureus (n = 8, 15.4%). The identified bacterial isolates showed high level of resistance against the antibiotics initiated at the start of the treatment, while resistance against piperacillin+tazobactam, imipenem, vancomycin and linezolid was very low. Just under half of the patients (n = 280, 47.8%) successfully completed the treatment (i.e., discharged with treatment success), while 123 (21%) patients died during treatment. In multivariable binary logistic regression, the factors which still remained significantly associated with neonatal death included, preterm delivery (AOR 9.59; 95% CI 4.41, 20.84), sub-optimal birth weight (AOR 5.13; 95% CI 2.19, 12.04), early onset sepsis (AOR 2.99; 95% CI 1.39, 6.41) and length of hospital stay (AOR 0.76; 95% CI 0.67, 0.88). Conclusion The mortality rate associated with sepsis was high in our study cohort. The bacterial isolates showed high level of resistance against the antibiotics started as the empiric therapy. Rational use of antibiotics can decrease the adverse outcomes in neonatal sepsis patients.
Role of the Nucleus Basalis as a Key Network Node in Temporal Lobe Epilepsy

Objective To determine whether the nucleus basalis of Meynert (NBM) may be a key network structure of altered functional connectivity in temporal lobe epilepsy (TLE), we examined fMRI with network-based analyses. Methods We acquired resting-state fMRI in 40 adults with TLE and 40 matched healthy control participants. We calculated functional connectivity of NBM and used multiple complementary network-based analyses to explore the importance of NBM in TLE networks without biasing our results by our approach. We compared patients to controls and examined associations of network properties with disease metrics and neurocognitive testing. Results We observed marked decreases in connectivity between NBM and the rest of the brain in patients with TLE (0.91 ± 0.88, mean ± SD) vs controls (1.96 ± 1.13, p < 0.001, t test). Larger decreases in connectivity between NBM and fronto-parietal-insular regions were associated with higher frequency of consciousness-impairing seizures (r = −0.41, p = 0.008, Pearson). A core network of altered nodes in TLE included NBM ipsilateral to the epileptogenic side and bilateral limbic structures. Furthermore, normal community affiliation of ipsilateral NBM was lost in patients, and this structure displayed the most altered clustering coefficient of any node examined (3.46 ± 1.17 in controls vs 2.23 ± 0.93 in patients). Abnormal connectivity between NBM and subcortical arousal community was associated with modest neurocognitive deficits. Finally, a logistic regression model incorporating connectivity properties of ipsilateral NBM successfully distinguished patients from control datasets with moderately high accuracy (78%). Conclusions These results suggest that while NBM is rarely studied in epilepsy, it may be one of the most perturbed network nodes in TLE, contributing to widespread neural effects in this disabling disorder.
Chemosensitization of HT29 and HT29-5FU Cell Lines by a Combination of a Multi-Tyrosine Kinase Inhibitor and 5FU Downregulates ABCC1 and Inhibits PIK3CA in Light of Their Importance in Saudi Colorectal Cancer

Colorectal cancer (CRC) remains one of the main causes of death worldwide and in Saudi Arabia. The toxicity and the development of resistance against 5 fluorouracil 5FU pose increasing therapeutic difficulties, which necessitates the development of personalized drugs and drug combinations. Objectives: First, to determine the most important kinases and kinase pathways, and the amount of ABC transporters and KRAS in samples taken from Saudi CRC patients. Second, to investigate the chemosensitizing effect of LY294002 and HAA2020 and their combinations with 5FU on HT29, HT29-5FU, HCT116, and HCT116-5FU CRC cells, their effect on the three ABC transporters, cell cycle, and apoptosis, in light of the important kinase pathways resulting from the first part of this study. Methods: The PamChip® peptide micro-array profiling was used to determine the level of kinase and targets in the Saudi CRC samples. Next, RT-PCR, MTT cytotoxicity, Western blotting, perturbation of cell cycle, annexin V, and immunofluorescence assays were used to investigate the effect on CRC, MRC5, and HUVEC cells. Results: The kinase activity profiling highlighted the importance of the PI3K/AKT, MAPK, and the growth factors pathways in the Saudi CRC samples. PIK3CA was the most overexpressed, and it was associated with increased level of mutated KRAS and the three ABC transporters, especially ABCC1 in the Saudi samples. Next, combining HAA2020 with 5FU exhibited the best synergistic and resistance-reversal effect in the four CRC cells, and the highest selectivity indices compared to MRC5 and HUVEC normal cells. Additionally, HAA2020 with 5FU exerted significant inhibition of ABCC1 in the four CRC cells, and inhibition of PIK3CA/AKT/MAPK7/ERK in HT29 and HT29-5FU cells. The combination also inhibited EGFR, increased the preG1/S cell cycle phases, apoptosis, and caspase 8 in HT29 cells, while it increased the G1 phase, p21/p27, and apoptosis in HT29-5FU cells. Conclusion: We have combined the PamChip kinase profiling of Saudi CRC samples with in vitro drug combination studies in four CRC cells, highlighting the importance of targeting PIK3CA and ABCC1 for Saudi CRC patients, especially given that the overexpression of PIK3CA mutations was previously linked with the lack of activity for the anti-EGFRs as first line treatment for CRC patients. The combination of HAA2020 and 5FU has selectively sensitized the four CRC cells to 5FU and could be further studied.
Net charge tuning modulates the antiplasmodial and anticancer properties of peptides derived from scorpion venom

VmCT1, a linear helical antimicrobial peptide isolated from the venom of the scorpion Vaejovis mexicanus, displays broad spectrum antimicrobial activity against bacteria, fungi, and protozoa. Analogs derived from this peptide containing single Arg‐substitutions have been shown to increase antimicrobial and antiparasitic activities against Trypanossoma cruzi. Here, we tested these analogs against malaria, an infectious disease caused by Plasmodium protozoa, and assessed their antitumoral properties. Specifically, we tested VmCT1 synthetic variants [Arg]3‐VmCT1‐NH2, [Arg]7‐VmCT1‐NH2, and [Arg]11‐VmCT1‐NH2, against Plasmodium gallinaceum sporozoites and MCF‐7 mammary cancer cells. Our screen identified peptides [Arg]3‐VmCT1‐NH2 and [Arg]7‐VmCT1‐NH2 as potent antiplasmodial agents (IC50 of 0.57 and 0.51 μmol L−1, respectively), whereas [Arg]11‐VmCT1‐NH2 did not show activity against P. gallinaceum sporozoites. Interestingly, all peptides presented activity against MCF‐7 and displayed lower cytotoxicity toward healthy cells. We demonstrate that increasing the net positive charge of VmCT1, through arginine substitutions, modulates the biological properties of this peptide family yielding novel antiplasmodial and antitumoral molecules.
Baseline monocyte and its classical subtype may predict efficacy of PD-1/PD-L1 inhibitor in cancers

Abstract Background: Programmed death 1 (PD-1)/ programmed death-ligand 1 (PD-L1) inhibitor is one of the most popular immune therapies. Biomarkers for predicting response are highly needed, but no biomarkers are widely used till now. Patients and methods: From February 2018 to April 2019, pan-cancer patients treated with PD-1 or PD-L1 inhibitor as a single agent in our center were included. The benefit group included patients with partial response, complete response and stable disease, while the patients with progressive disease were classified into the nonbenefit group, according to the RECIST 1.1 criteria. Baseline peripheral blood was sampled to determine absolute monocyte count (AMC) and/or classical monocyte frequency (CMF) of peripheral blood mononuclear cells. Then, the association of the above-mentioned two biomarkers with response or progression-free survival (PFS) was evaluated. Results: In total, 107 patients enrolled in the present study. The nonbenefit group had significantly larger number of AMC than benefit group (P<0.001), and patients with higher AMC had decreased PFS time (P=0.001). Of 39 patients tested for CMF, the nonbenefit group had significantly higher CMF than benefit group (P=0.002), and patients with higher CMF had significantly decreased PFS time (P=0.002). The sensitivity of AMC and CMF was 87.9% and 85.7%, respectively, and the specificity was 44.9% and 61.1%, respectively. Multivariate analysis showed high baseline CMF and AMC were both significantly associated with decreased PFS time. Conclusion: Baseline CMF and baseline AMC can be potential pan-cancer biomarkers to predict efficacy of PD-1/PD-L1 inhibitors, especially in the PD-L1 subgroup.
Crystallogeometry of polymorphic transitions in silicon under pressure

Abstract Under shear deformation direct transitions SiI → SiIV → SiIII are observed; orientation relationships (OR) between phases have been determined for these transitions. It is shown, that the complete set of OR between phases SiI and SiIV contains six variants. On the basis of the obtained experimental data, a P-T-[sgrave]-diagram has been constructed for Si, that allows to explain phase transitions characteristics at temperatures T<0, 3T (melting).
School-based interventions modestly increase physical activity and cardiorespiratory fitness but are least effective for youth who need them most: an individual participant pooled analysis of 20 controlled trials

Objectives To determine if subpopulations of students benefit equally from school-based physical activity interventions in terms of cardiorespiratory fitness and physical activity. To examine if physical activity intensity mediates improvements in cardiorespiratory fitness. Design Pooled analysis of individual participant data from controlled trials that assessed the impact of school-based physical activity interventions on cardiorespiratory fitness and device-measured physical activity. Participants Data for 6621 children and adolescents aged 4–18 years from 20 trials were included. Main outcome measures Peak oxygen consumption (VO2Peak mL/kg/min) and minutes of moderate and vigorous physical activity. Results Interventions modestly improved students’ cardiorespiratory fitness by 0.47 mL/kg/min (95% CI 0.33 to 0.61), but the effects were not distributed equally across subpopulations. Girls and older students benefited less than boys and younger students, respectively. Students with lower levels of initial fitness, and those with higher levels of baseline physical activity benefitted more than those who were initially fitter and less active, respectively. Interventions had a modest positive effect on physical activity with approximately one additional minute per day of both moderate and vigorous physical activity. Changes in vigorous, but not moderate intensity, physical activity explained a small amount (~5%) of the intervention effect on cardiorespiratory fitness. Conclusions Future interventions should include targeted strategies to address the needs of girls and older students. Interventions may also be improved by promoting more vigorous intensity physical activity. Interventions could mitigate declining youth cardiorespiratory fitness, increase physical activity and promote cardiovascular health if they can be delivered equitably and their effects sustained at the population level.
Pediatric weight estimation: validation of the PAWPER XL tape and the PAWPER XL tape mid-arm circumference method in a South African hospital

Objective The primary aim of this study was to prospectively compare the performance of the Broselow tape, Mercy method, pediatric advanced weight prediction in the emergency room extra-long (PAWPER XL) tape, and PAWPER XL mid-arm circumference (MAC) method in estimating the weight of children from a low-income setting. The secondary aim was to analyze the time taken to perform each method. Methods This analyzed a convenience study sample of 300 children aged 0 to 18 years at the Baragwanath Hospital in South Africa. Weight estimations were obtained using each of the weight estimation systems on each child. These weight estimations were then compared against the actual weight to determine bias, precision, and accuracy of the estimation methods. Results The PAWPER XL tape and PAWPER XL-MAC methods performed the best and provided estimated weights within 10% of the actual weight in 62.7% and 67.3% of cases, respectively, followed by the Mercy method (56.5%) and Broselow tape (43.9%). The use of MAC improved the accuracy of estimation, especially in heavier and taller children. The median times taken to perform measurements using the Broselow tape, Mercy method, PAWPER XL tape, and PAWPER XL-MAC method were 11.3 seconds, 34.7 seconds, 9.3 seconds, and 33.9 seconds respectively. Conclusion The PAWPER XL tape and PAWPER XL-MAC methods were the most accurate methods of estimating weight in this group of children. These methods may be considered in preference to the Broselow tape or the Mercy method for emergency weight estimation in low socioeconomic status populations.
Impact of Educational Technology on Teacher Stress and Anxiety: A Literature Review

Educational technology has become an increasingly important element for improving the teaching and learning process of students. To achieve these goals, it is essential that teachers have the skills they need to be able to introduce technology into their teaching practice. However, this is often overwhelming and stressful for many of them. The aim of this review was to find out how research on teacher stress and anxiety associated with the use of educational technology was proceeding. A systematic review was conducted using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines through the following bibliographic databases: PubMed, Web of Science, and Scopus. Sixteen articles were found from the review. The main findings show that teachers present high levels of anxiety or stress due to their use of educational technology in the classroom. Among the conclusions, the need for research on different strategies to prevent the emergence of these anxiety and stress symptoms in teachers stands out.
Echocardiographic estimation of left ventricular-arterial coupling in dogs with myxomatous mitral valve disease.

BACKGROUND The effective arterial elastance (Ea) to left ventricular (LV) end-systolic elastance (Ees) ratio (Ea/Ees) is an index of the interaction between LV and systemic arterial systems, left ventricular-arterial coupling (VAC). The Ea is an index of total arterial load of the LV, whereas Ees is an index of LV systolic function. In humans, inappropriate VAC based on increased Ea/Ees estimated using echocardiography is associated with more advanced heart disease severity. HYPOTHESIS Left ventricular-arterial coupling assessed by echocardiographic estimation of Ea/Ees is associated with disease severity in dogs with myxomatous mitral valve disease (MMVD). ANIMALS Ninety MMVD dogs and 61 healthy dogs. METHODS Prospective cross-sectional study. The MMVD dogs were classified into stages B1, B2, or C according to American College of Veterinary Internal Medicine guidelines. Effective arterial elastance was echocardiographically estimated using the formula: mean blood pressure/(forward stroke volume/body weight). End-systolic elastance was echocardiographically estimated using the formula: mean blood pressure/(LV end-systolic volume/body weight). The ratio Ea/Ees was calculated. RESULTS The ratio Ea/Ees was higher in stage B2 dogs than in healthy dogs and dogs stage B1 (both P < .0001), and higher in stage C dogs than in healthy dogs and dogs in the other 2 stages (healthy vs C and B1 vs C, P < .0001; B2 vs C, P = .0005). Multivariable logistic regression analysis showed that Ea/Ees and the peak velocity of early diastolic transmitral flow to isovolumic relaxation time ratio were independent predictors of stage C among echocardiographic indices in MMVD dogs. CONCLUSIONS AND CLINICAL IMPORTANCE Inappropriate VAC assessed by echocardiographically estimated Ea/Ees is associated with advanced disease severity in dogs with MMVD.
Depression in Bangladeshi university students: The role of sociodemographic, personal, and familial psychopathological factors.

PURPOSE Although depression has adverse effects on all aspects of university students' quality of life, fewer studies have been conducted in Bangladesh; which was investigated herein. DESIGN AND METHODS: A cross-sectional study was carried out among 1844 students enrolled at the University of Dhaka, Bangladesh. Hierarchical regression analyses were performed to investigate the explanatory power of the variables predicting depression in this population. FINDINGS Depression prevalence was 28.7%; and female gender, first-year student status, substance use, past-year physical and psychological illness, stressful life events, family psychiatric history, and personal suicidal behaviors were the main risk factors. The final model considering all the studied variables explained 23.5% of the variance in depression. PRACTICAL IMPLICATIONS: Effective psychological help services, awareness and intervention programs, and so on, should be implemented to reduce students' psychological burdens.