Miracle-dz/UniFAR-FTUs huggingface dataset:
Performance of the Arabic Population on the Adolescent-Adult Sensory Profile: An Observational Study

Background The Adult-Adolescent Sensory Profile (AASP) is a questionnaire developed to measure the way in which people in different age groups respond to different sensory stimuli. These sensory stimuli may uncover different behavioral problems that may affect activities of daily living. This observational study aimed to validate the Arabic version of the AASP used to assess the sensory processing abilities of healthy individuals. Methods Participants comprised 560 Jordanians aged 11 years and older. Participants were recruited from different community centers in Amman, Jordan during 10th March 2017 to 10th September 2017. The English version of the AASP was translated into Arabic and all participants were instructed to complete this version of the scale. Results Internal consistency was 0.78 and 0.79 for the Arabic and the English version, respectively. The ranges of cut-off scores in the Arabic version were higher than the English version for all the quadrants of the scale. The biggest differences were found in the sensation seeking and sensory sensitivity quadrants. In certain age groups (11–17 and 18–64 years), women were more sensitive compared with men. Conclusion The Arabic version of the AASP showed good internal consistency and can be used to assess the sensory processing abilities of healthy individuals.
Willingness to Join and Pay for Community-Based Health Insurance Among Rural Households of Selected Districts of Jimma Zone, Southwest Ethiopia

Background Globally, millions of people suffer and die because they do not have the money to pay for health care. A voluntary health insurance scheme is a prepayment mechanism to overcome the financial hardship of poor households. There is a high demand to determine the enrolment rate and ability to pay before scale-up of the scheme by the government to be sure of its feasibility and sustainability. Objective To determine willingness to join and pay for a community-based health insurance scheme and associated factors among rural households of selected districts in Jimma Zone, 2018. Methods A community-based cross-sectional study design was employed in selected districts of Jimma Zone, Ethiopia. Multistage simple random sampling was used to select 422 households. Data were collected using a semi-structured interviewer-administered questionnaire. A double bounded contingent valuation method was applied to elicit households’ willingness to pay for the scheme. Data were entered into Epi-Data 3.1 and analyzed with SPSS V.23. A binary logistic regression model was fitted to determine the presence of statistically significant associations between the dependent and independent variables at p-value <0.05 and AOR values with 95% CI. Results Of 422 sampled respondents, 389 participated in this study with a response rate of 92%. Of these, 305 (78%) were willing to join and 274 (90%) of them were willing to pay. The average amount of money the households were willing to pay per household per annum was 228 ETB (8.27 USD), with a range of 100–500 ETB. The older age groups, poor households, and experience of local risk-sharing schemes were found to be determinants for willingness to join the community-based health insurance. Similarly, having a large family size, and low economic and education status of households were significant predictors of willingness to pay for this scheme. Conclusion A high proportion of households were willing to join and pay for the CBHI scheme. The average amount of money they were willing to pay for the scheme was very slightly lower than what is planned by the government. Thus, the government of Ethiopia should strengthen efforts to scale up this scheme in the rural areas of the country specifically to districts not yet enrolled, to reduce direct out-of-pocket payment at service delivery points. This will also contribute to guaranteeing dwellers of rural areas access to quality health services without facing financial hardship, to achieve universal health coverage for all by the end of 2035.
Nitroxide-Modified Protein-Incorporated Nanoflowers with Dual Enzyme-Like Activities

Purpose Combined superoxide dismutase (SOD)/catalase mimetics have attracted much attention because of their efficacy against reactive oxygen species-associated diseases; however, their application is often limited owing to their poor stability and the absence of favorable grafting sites. To address this, we developed a new class of SOD/catalase mimetics based on hybrid nanoflowers, which exhibit superior stability and possess the desired grafting sites for drugs and endogenous molecules. Methods In this work, for the first time, we used polynitroxylated human serum albumin (PNA) to mediate the formation of hybrid copper-based nanoflowers. H2O2 depletion and O2 evolution assays were first performed to determine the catalase-like activity of the hybrid nanoflowers. Next, the xanthine oxidase/cytochrome c method was used to assay the SOD-like activity of the nanoflowers. Further characteristics of the nanoflowers were evaluated using scanning electron microscopy (SEM), electron paramagnetic resonance (EPR), and Fourier-transform infrared spectroscopy (FTIR). Operational stability was assessed via the reusability assay. Results The H2O2 depletion and O2 evolution assays indicated that PNA-incorporated nanoflowers have genuine catalase-like activity. Kinetic analysis revealed that the reactions of the incorporated nanoflowers with H2O2 not only obey Michaelis–Menton kinetics, but that the nanoflowers also possess a higher affinity for H2O2 than that of native catalase. The FTIR spectra corroborated the presence of PNA in the hybrid nanoflowers, while the EPR spectra confirmed the intermolecular interaction of nitroxides bound to the human serum albumin incorporated into the nanoflowers. The remarkable operational reproducibility of the hybrid nanoflowers in catalase-like and SOD-like reactions was verified across successive batches. Conclusion Herein, a comparison of Michaelis constants showed that the hybrid nanoflower, a catalase mimetics, outperforms the native catalase. Acting as a “better-than-nature” enzyme mimetics, the hybrid nanoflower with superior stability and desired ligand grafting sites will find widespread utilization in the medical sciences.
Exon Coverage Variations Between Cancer Tissues and Adjacent Non-Cancerous Tissues are Prognostic Factors in Gastric Cancer

Introduction Gastric cancer is highly heterogeneous both clinically and pathologically and is one of the leading causes of cancer-related deaths worldwide. Genomic coverage variations, also known as copy number variations (CNVs), play a critical role in the carcinogenesis of gastric cancer. Many studies have demonstrated that DNA CNVs are important factors affecting the expression of protein-encoding genes in the gastric cancer genome. Methods Thirty gastric cancer patients from a Chinese population were enrolled. Genomic DNA was extracted from gastric cancer tissue and matched adjacent non-cancerous tissue from each patient. A panel of 1,021 genes including 3300 exons was designed and subjected to next-generation sequencing. Copy numbers of each gene and exon were calculated for each tissue. Coverage variations between gastric cancer tissue and matched adjacent non-cancerous tissue were also calculated, and we examined the correlation between overall survival of patients and coverage variation type for each exon. Results DNA from cancerous tissue and corresponding adjacent non-cancerous tissue were significantly different with respect to the pattern of gene copy number. Exon copy numbers were highly consistent among non-cancerous samples and confirmed that non-cancerous tissue contain diploid genomes. In contrast, the gene coverage pattern among cancerous tissue showed significant differences and confirmed that gastric cancer is a genetically heterogeneous disease. Numerous exon coverage variations were identified in gastric cancer tissue compared with matched, adjacent non-cancerous tissue. Overall survival between patients with and without coverage variations in regions of NOTCH2, NTRK3, ERBB2 and RERE exons exhibited significant differences. This is consistent with previous reports and indicates that these findings may have prognostic value. Conclusion Our results confirm that gastric cancer is a genetically heterogeneous disease. Exon coverage variations between cancer tissue and their adjacent non-cancerous tissue were shown to be associated with prognosis in gastric cancer.
Supply Chain Management Performance of HIV/AIDS Commodities and Factors Affecting It at Health Facilities of SNNPRS of Ethiopia; from the Perspective of Achieving 90-90-90 Strategies

Background Health facilities (HFs) need an extensive range of antiretroviral (ARV) drugs and related HIV/AIDS commodities for diagnosis, prevention, and treatment of HIV/AIDS. This study was aimed to assess supply chain management performance from the perspective of achieving 90-90-90 treatment strategy at HFs of Southern Nations, Nationalities and People’s Regional State (SNNPRS), Ethiopia. Methods Facilities based cross sectional study design in 30 HFs (9 hospitals and 21 health centers) and five pharmaceuticals fund and supply agencies (PFSAs) was conducted. The HFs were selected randomly. Semi-structured questionnaires and observation checklists with logistic indicators assessment tools (LIATs) were used to collect data for HIV/AIDS related services from November 2016 to May 2017. In addition, we used in-depth face to face interview and thematic approach. Quantitative data were entered into Epi-Data version 3.1 and transported to SPSS version 20 to analyze the result. Qualitative data were analyzed using thematic approach. Results Only 9 (30%) HFs had received their orders from PFSA on time from date of report. Average lead time for ARV drugs was 46.4 days in hospitals and 59.2 days in health centers (HCs). Sixteen (60.7%) HFs reported their completed report and requisition format (RRF). From this, 53.3% HFs order was refilled correctly in quantity from that they need. Inventory accuracy rate was 77%. Major HFs, 20 (66.7%) faced at least one-time emergency order for ARV drugs, HIV test kits and viral load (VL) supplies. Whereas, 9 (30%) hospitals and 5 (16.67%) HCs were out of stock two and three times respectively. Sixteen (53.3%) commodities stocked out at least once in six months. Nevirapine (NVP) 10 mg/5 mL in 240 mL was the most stocked out (13 times) for an average 22 days. Uni gold was stocked out (16 times) with average of 34.5 days. Wastage rate was 2.5%. Twenty-five (83.3%) facilities had good storage conditions (>80% to the standard). Conclusion Unsatisfactory data records, stock-outs, interrupted reports, inaccurate inventory and wastage rates were indicators for defective supply chain management of HIV/AIDS commodities. Respective organizations should improve their responsible activities to secure commodities availability.
Water Extract of Sporoderm-Broken Spores of Ganoderma lucidum Induces Osteosarcoma Apoptosis and Restricts Autophagic Flux

Purpose Osteosarcoma (OS) is a malignant bone tumor with easy metastasis and poor prognosis. Ganoderma lucidum (G. lucidum), a traditional Chinese medicine, was reported playing a critical role in suppressing multiple tumor progress. So we wanted to investigate the effects and molecular mechanisms of water extract of sporoderm-broken spores of G. lucidum (BSGLWE) on osteosarcoma. Methods In vitro, the effects on cell proliferation of BSGLWE in osteosarcoma cells were detected by CCK-8, colony formation assay and flow cytometry; migration ability of osteosarcoma cells was evaluated by cell scratch and transwell assays. Cell apoptosis and autophagy were tested by transmission electron microscopy (TEM). Potential signaling pathways were detected by Western blotting and immunofluorescence. In xenograft orthotopic model, the luminescence intensity measured by an in vivo bioluminescence imaging system, and the expression of related proteins in tumor cells were assessed by IHC analysis. Results BSGLWE suppressed the proliferation and migration of osteosarcoma cells in a dose-dependent manner, and osteosarcoma cell cycle progression at the G2/M phase was arrested by the BSGLWE. In addition, increased apoptosis-related protein expression meant BSFLWE induced caspase-dependent apoptosis of osteosarcoma cells. TEM results indicated that BSGLWE promoted the formation of apoptotic bodies and autophagosomes in HOS and U2 cells. Western blotting or immunofluorescence and rescue assay revealed that BSGLWE blocked autophagic flux by inducing initiation of autophagy and increasing autophagosome accumulation of osteosarcoma cells. BSGLWE not only repressed the angiogenesis in the mouse model, but also induced apoptosis and blocked autophagy in vivo. Conclusion BSGLWE inhibits osteosarcoma progression.
Virulence and biofilms as promising targets in developing antipathogenic drugs against candidiasis

Candida albicans has remained the main etiological agent of candidiasis, challenges clinicians with high mortality and morbidity. The emergence of resistance to antifungal drugs, toxicity and lower efficacy have all contributed to an urgent need to develop alternative drugs aiming at novel targets in C. albicans. Targeting the production of virulence factors, which are essential processes for infectious agents, represents an attractive substitute for the development of newer anti-infectives. The present review highlights the recent developments made in the understanding of the pathogenicity of C. albicans. Production of hydrolytic enzymes, morphogenesis and biofilm formation, along with their molecular and metabolic regulation in Candida are discussed with regard to the development of novel antipathogenic drugs against candidiasis.
Dual Targeting of the Epidermal Growth Factor Receptor Using Combination of Nimotuzumab and Erlotinib in Advanced Non-Small-Cell Lung Cancer with Leptomeningeal Metastases: A Report of Three Cases

Abstract Leptomeningeal metastases (LM) occur in 3–5% of patients with advanced non-small-cell lung cancer (NSCLC) and are associated with a dismal prognosis. We report three cases of NSCLC with LM who were treated with the combination of nimotuzumab and erlotinib. Magnetic Resonance Imaging (MRI) evaluation during follow-up showed significant improvement in cancer symptoms and decreased tumor size in all three patients. Grade 3 and 4 toxicities were rarely seen. Based on apparent efficacy of the regimen and fewer side effects, we suggest that nimotuzumab in combination with erlotinib may be a promising option for the treatment of NSCLC with LM.
Comparison of Gut Microbiome in Human Colorectal Cancer in Paired Tumor and Adjacent Normal Tissues

Background To understand the biological effect of gut microbiome on the progression of colorectal cancer (CRC), we sequenced the V3-V4 region of the 16S rRNA gene to illustrate the overall structure of microbiota in the CRC patients. Methods In this study, a total of 66 CRC patients were dichotomized into different groups based on the following characteristics: paired tumor and adjacent normal tissues, distal and proximal CRC segments, MMR (-) and MMR (+), different TNM staging and clinic tumor staging. Results By sequencing and comparing the microbial assemblages, our results indicated that 7 microbe genus (Fusobacterium, Faecalibacterium, Akkermansia, Ruminococcus2, Parabacteroides, Streptococcus, and f_Ruminococcaceae) were significantly different between tumor and adjacent normal tissues; and 5 microbe genus (Bacteroides, Fusobacterium, Faecalibacterium, Parabacteroides, and Ruminococcus2) were significantly different between distal and proximal CRC segments; only 2 microbe genus (f_Enterobacteriaceae and Granulicatella) were significantly different between MMR (-) and MMR (+); but there was no significant microbial difference were detected neither in the TNM staging nor in the clinic tumor staging. Conclusion All these findings implied a better understanding of the alteration in the gut microbiome, which may offer new insight into diagnosing and therapying for CRC patients.
BTLA Expression in Stage I–III Non–Small-Cell Lung Cancer and Its Correlation with PD-1/PD-L1 and Clinical Outcomes

Background B and T lymphocyte attenuator (BTLA) is a novel immune checkpoint with an unclear role in non–small-cell lung cancer (NSCLC). In contrast, the programmed death-1 (PD-1)/programmed death ligand-1 (PD-L1) checkpoint is a potentially curative immunotherapy target in NSCLC. Our study investigated BTLA expression and its relationship with PD-1/PD-L1, tumor-infiltrating lymphocytes (TILs), and clinicopathological features. Methods The protein expressions of BTLA, PD-1, and PD-L1 were evaluated by immunohistochemistry (IHC) and TIL abundance was scored in paraffin-embedded tissues from surgically resected specimens from 87 patients with stage I–III NSCLC. Results BTLA was expressed in tumor cells in 35 patients with NSCLC (40.2%). In addition, 42 patients (48.3%) were positive for PD-1 in TILs and 31 (35.6%) were positive for PD-L1 in tumor cells. BTLA was overexpressed in patients with lymphatic invasion (P=0.045) and an advanced tumor stage (P=0.034). High expression of BTLA was positively correlated with a high level of PD-L1 (P=0.011). Patients with positive BTLA expression had a shorter relapse-free survival (RFS) than those with negative BTLA expression (P=0.029). Moreover, patients negative for both BTLA and PD-L1 had a longer RFS than patients who were positive for BTLA or PD-L1 or for both checkpoints (P=0.012). The same pattern was shown for overall survival (P=0.031). Conclusion High BTLA expression may predict poor prognosis in patients with NSCLC and may represent a new immunotherapy target.
Sevoflurane Inhibits Proliferation and Invasion of Human Ovarian Cancer Cells by Regulating JNK and p38 MAPK Signaling Pathway

Aim Sevoflurane is a halogen inhaled anesthetic, and we aimed to probe the effect of sevoflurane on proliferation and invasion of human ovarian cancer (OC) and its mechanism. Methods OC cell lines were divided into 4 groups including control, sevoflurane low concentration (1.7%), medium concentration (3.4%) and high concentration (5.1%) groups. Flow cytometry and MTT assay were, respectively, employed to detect the cell apoptosis and proliferation. Transwell assay was applied to measure the cell migration and invasion viability. The gene and protein expressions were assessed using qRT-PCR and Western blot. The expressions of MAPK signaling pathway-related proteins were evaluated by Western blot. The p38 and JNK inhibitors were, respectively, added into the high concentration group to analyze the relationship between sevoflurane and modulatingmitogen-activated protein kinase (MAPK) pathway in OC. Nude mice models were constructed to explore the effect of sevoflurane on OC tumor growth in vivo. Results Sevoflurane inhibited OC proliferation in vitro and in vivo. It could also promote OC cell apoptosis in a dose-dependent manner. Sevoflurane suppressed the OC cell migration and invasion, and these effects were positively correlated with the dose of sevoflurane. Moreover, sevoflurane treatment inhibited the expressions of PCNA, Twist, cleaved-caspase-3/caspase-3, MMP-2 and MMP-9. In addition, sevoflurane repressed the phosphorylation of JNK and p38 MAPK. When the MAPK pathway was interdicted, the cell proliferation, apoptosis, migration and invasion activity were recovered after sevoflurane treatment. Conclusion Sevoflurane affected cell biological activities in OC by regulating JNK and p38 MAPK signaling pathway.
Extraglycemic Effects of SGLT2 Inhibitors: A Review of the Evidence

Abstract Patients with type 2 diabetes (T2D) are often overweight/obese and affected by arterial hypertension, dyslipidaemia, and have high serum levels of uric acid. Moreover, T2D patient have a higher risk of developing cardiovascular or renal complications, which are leading causes of morbidity and mortality in this population. Sodium-glucose cotransporter-2 inhibitors (SGLT2i) are a new class of glucose-lowering medications that block the reabsorption of glucose in the kidney, thereby increasing urinary glucose excretion, and lowering blood glucose levels. The beneficial effects of SGLT2 inhibition extend beyond glycaemic control, and include improvement in blood pressure, body weight, uric acid concentrations, liver steatosis, oxidative stress, and inflammation. In dedicated cardiovascular outcome trials, SGLT2i treatment was associated with a significant reduction in the rate of cardiovascular events and renal endpoints. In this review, we summarize the evidence for extra-glycemic effects of SGLT2i and the potential mechanisms driving cardiorenal protection exerted by this class of medications.
Epstein-Barr virus miR-BART1-3p suppresses apoptosis and promotes migration of gastric carcinoma cells by targeting DAB2

Although Epstein-Barr virus (EBV) is known to encode over 40 different miRNAs of its own, the roles of most EBV miRNAs remain unknown. Disabled homolog 2 (DAB2) is a putative tumor suppressor, but its role in gastric carcinoma (GC), especially in EBV-associated GC, needs to be clarified. Our qRT-PCR and mRNA microarray results showed that DAB2 expression was down-regulated in EBV-positive GC cells compared to EBV-negative cells. Four BART miRNAs that might target DAB2 were predicted, and we found, using a luciferase reporter assay, that miR-BART1-3p directly targeted the 3'-UTR of DAB2. The miR-BART1-3p transfection decreased DAB2 expression at both mRNA and protein levels, while transfection of an inhibitor of miR-BART1-3p, miR-BART1-3p(i), increased DAB2 expression. In addition, miR-BART1-3p as well as siDAB2 increased migration and decreased apoptosis. Meanwhile, miR-BART1-3p(i) or pcDNA3.1-DAB2 transfection decreased migration and increased apoptosis in EBV-infected GC cells. Furthermore, decreased migration by miR-BART1-3p(i) was abrogated by co-transfected siDAB2, while decreased migration by miR-BART1-3p(i) was further suppressed by a co-transfected DAB2 over-expression vector. Our data suggest that miR-BART1-3p plays an important role in the tumorigenesis of EBV-associated GC by directly targeting DAB2.
Comparative Efficacy and Safety of Dupilumab and Benralizumab in Patients with Inadequately Controlled Asthma: A Systematic Review

No head-to-head trials have compared the efficacy and safety between the licensed dosage and administration dosage of dupilumab and benralizumab for inadequately controlled asthma. We conducted an indirect treatment comparison to estimate differences in the efficacy and safety between dupilumab and benralizumab for inadequately controlled asthma using the Bayesian approach. The primary efficacy endpoint was annual exacerbation rate (AER). A subgroup analysis by blood eosinophil count was also performed. The primary safety endpoint was the incidence of any adverse events (AAEs). The results demonstrate that there was no significant difference in the AER between dupilumab and benralizumab in overall patients and the subgroup with the blood eosinophil count of <150. However, the AER was significantly lower in the dupilumab group than in the benralizumab group in the subgroup with a blood eosinophil count of ≥150 but <300, and ≥300 with the rate ratio and 95% credible interval of 0.51 (0.29–0.92) and 0.58 (0.39–0.84), respectively. There was no significant difference in the AAEs between the dupilumab and benralizumab groups. This indirect treatment comparison indicates that dupilumab is superior to benralizumab in patients with inadequately controlled asthma having higher blood eosinophil counts. A direct comparison is required to provide definitive evidence. Systematic Review Registration: UMIN-CTR no. UMIN000036256.