Miracle-dz/UniFAR-FTUs huggingface dataset:
Induction of G2/M Cell Cycle Arrest and Apoptosis by Genistein in Human Bladder Cancer T24 Cells through Inhibition of the ROS-Dependent PI3k/Akt Signal Transduction Pathway

We examined the anti-cancer effect of genistein, a soy-derived isoflavone, in human bladder transitional cell carcinoma T24 cells. According to our data, genistein induced G2/M phase arrest of the cell cycle and apoptosis. Genistein down-regulated the levels of cyclin A and cyclin B1, but up-regulated the levels of p21WAF1/CIP1, cyclin-dependent kinase (Cdk) inhibitor, that was complexed with Cdc2 and Cdk2. Furthermore, genistein induced the activation of caspases (caspase-3, -8 and -9), and cleavage of poly (ADP-ribose) polymerase cleavage. However, genistein-induced apoptosis was significantly inhibited by a pan-caspase inhibitor, indicating that the induction of apoptosis by genestein was caspase-dependent. In addition, genistein increased the cytosolic release of cytochrome c by increasing the Bax/Bcl-2 ratio and destroying mitochondria integrity. Moreover, genistein inactivated the phosphoinositide 3-kinase (PI3K)/Akt signaling pathway, while LY294002, a PI3K/Akt inhibitor, increased the apoptosis-inducing effect of genistein. Genistein further increased the accumulation of reactive oxygen species (ROS), which was significantly suppressed by N-acetyl cysteine (NAC), a ROS scavenger, and in particular, NAC prevented genistein-mediated inactivation of PI3K/Akt signaling, G2/M arrest and apoptosis. Therefore, the present results indicated that genistein promoted apoptosis induction in human bladder cancer T24 cells, which was associated with G2/M phase cell cycle arrest via regulation of ROS-dependent PI3K/Akt signaling pathway.
How and in what Contexts Does Networked Health IT Improve Patient Safety? Elicitation of Theories from the Literature

Healthcare systems worldwide are investing in networked health IT systems that link healthcare providers across multiple organisations. Much of the policy arguments in favour of such investment rely on the assumption that networked health IT will lead to improved patient safety. As part of the first stage of a realist review to determine how and in what contexts networked, inter-organisational health IT does lead to improved patient safety, we elicited stakeholders' theories from the literature that reveal possible answers to this question. A key mechanism appears to be that the information provided supports improved decision making. Greatest benefits are likely to be found in relation to medication information, in scenarios where the patient is less able to provide accurate information about their medications themselves. However, access and use of this information depends on ease of access, clinicians' perception of the likelihood that the desired information will be available, and clinicians' trust in the information.
Neuromyelitis optica spectrum disorders with vertigo as the initial symptom

Abstract Rationale: Brain abnormalities have frequently been reported in neuromyelitis optica spectrum disorders patients, but vertigo as an initial manifestation has rarely been described. Patient concerns: A 64-year-old woman who initially presented with vertigo, then accompanied with other brainstem manifestations and spinal cord involvement. Diagnoses: MRI revealed medulla oblongata, cervical and thoracic spinal cord lesions. NMO-IgG antibody was seropositive. Taken her previous medical history and clinical manifestations into consideration, the patient was eventually diagnosed as neuromyelitis optica spectrum disorders. Interventions: Before diagnosis, symptomatic treatment and acupuncture were adopted, whereas after diagnosis, steroid, intravenous immunoglobulin, and immunosuppressant were supplemented. Outcomes: Her dizziness, nausea and vomiting were gradually relieved by symptomatic treatment and acupuncture before the confirmed diagnosis and immunotherapy. After added treatment with steroid, immunosuppressant, especially intravenous immunoglobulin, diplopia and nystagmus disappeared, and superficial sensation was improving. She was fully recovered six months after admission. Lessons: Vertigo as a rare prodrome of neuromyelitis optica spectrum disorders deserves attention. The symptoms and signs were improved by a combined treatment of steroid, immunosuppressant, acupuncture, and particularly intravenous immunoglobulin.
The prevalence of enamel and dentine caries lesions and their determinant factors among children living in fluoridated and non-fluoridated areas.

OBJECTIVE To determine the prevalence and severity of dental caries (at dentine and enamel levels of diagnosis) amongst Malaysian children and to investigate determinant factors associated with caries detection at these different thresholds. METHODS This study involved life-long residents aged 12 years-old in fluoridated and non-fluoridated areas in Malaysia (n=595). The survey was carried out in 16 public schools by a calibrated examiner, using ICDAS-II criteria. A questionnaire on socio-demographic and oral hygiene practices was self-administered by parents/guardians. Data were analysed using Mann-Whitney U tests and logistic regression. RESULTS The overall response rate was 74.4%. Caries prevalence at the dentine level or at the dentine and enamel level was significantly (p⟨0.001) higher among children in the non-fluoridated area (D₁₋₆MFT⟩0 = 82.4%, D₄₋₆MFT⟩0 = 53.5%) than in the fluoridated area (D₁₋₆MFT⟩0 = 68.7%, D₄₋₆MFT⟩0 = 25.5%). Considering only the decayed component of the index, no significant differences were observed between the two areas when the detection threshold was set at enamel caries (D₁₋₃) (p=0.506). However, when the detection criteria were elevated to the level of caries into dentine (D₄₋₆) there were clear differences between the fluoridated and non-fluoridated areas (p=0.006). Exposure to fluoridated water proved a significant predictor for lower caries prevalence in the statistical model. Children whose father and mother had a low monthly income had a significantly higher dentine caries prevalence. CONCLUSION Results confirmed existing evidence of the benefit of water fluoridation in caries prevention. Detection criteria set at caries into dentine shows clear differences between fluoridated and non-fluoridated areas. Exposure to fluoridated water and socio-economic status were associated with caries prevalence.
An Integrative Biomedical Informatics Approach to Elucidate the Similarities Between Pre-Eclampsia and Hypertension

Pre-eclampsia is a pregnancy condition affecting 5-10% of pregnancies, and it is the leading cause of death in pregnancy associated with increased risk of cardiovascular disease later in life. Despite research, the pathogenesis of pre-eclampsia is still poorly understood. In this paper, we investigate the overlapping pathogenic mechanisms between pre-eclampsia and adult hypertension using an integrative biomedical informatics strategy that combined text mining techniques to identify genes and proteins, with geneset analyses, generating knowledge on the pathways and mechanisms involved in these conditions. We identified several overlapping pathogenic pathways/systems including metabolic pathways, developmental biology pathways, immune system, haemostasis, tyrosine kinase pathways, extracellular matrix and oxidative stress pathways. This bioinformatics approach could be applied for investigating mechanistic pathways of other disorders.
Nanotribological Properties of Ga- and N-Faced Bulk Gallium Nitride Surfaces Determined by Nanoscratch Experiments

Through nanoscratch experiments with a spherical diamond indenter, a contrastive study of the nanotribological properties of Ga- and N-faced gallium nitride (GaN) samples was carried out. Nanoindentation results revealed that the elastic modulus of the Ga-faced GaN sample was slightly higher than that of N-faced GaN sample. Particularly, Ga- and N-faced GaN samples exhibited rather different nanotribological properties, and the Ga-faced sample showed a stronger wear resistance. The study indicated that the critical normal load required to cause material removal of N-faced GaN sample was almost two times that of Ga-faced GaN sample. Both Ga- and N-faces exhibited a rather low frictional coefficient at the elastic and elastoplastic stages of material, e.g., ~0.06 for Ga-face and ~0.075 for N-face when scratching under the progressive normal load. Combined with transmission electron microscopy and X-ray photoelectron spectroscopy, we speculated that, except for the intrinsic atomic arrangements attributed to the non-reverse crystallographic symmetry of c-plane wurtzite GaN, the difference of nanotribological properties between Ga- and N-faces may also be related to the preferential formation of a native oxide layer and a slight lattice damage layer on the N-faced GaN surface. This study can enrich the understanding of the nanotribological properties of Ga- and N-polar-faced bulk monocrystalline GaN materials fabricated by the conventional technique.
In situ composite ion-triggered gellan gum gel incorporating amino methacrylate copolymer microparticles: a therapeutic modality for buccal applicability

Abstract The aim of the current investigation is to delineate the buccal applicability of an in situ composite gel containing aceclofenac (AC) amino methacrylate copolymer microparticles (MPs), surmounting limitations of oral existing conventional therapy. AC Eudragit RL100 MPs were fabricated and statistically optimized using 2241 factorial design. Better buccal applicability and enhanced localization were achieved by combining the optimum MPs with in situ ion-activated gellan gum gel. The crosslinking and gelation of in situ gel were investigated by morphological and solid state characterizations. Suitability for buccal delivery and in vivo therapeutic efficacy in inflammation model of rats were also assessed. Results showed that the best performing formula displayed particle size (PS) of 51.00 µm and high entrapment efficiency (EE%) of 94.73%. MPs were successfully entrapped inside the gel network of the composite system. Gelation tendency, pH, shear-thinning properties and mucoadhesivity of the prepared in situ composite gel guaranteed its buccal suitability. Sustained AC release features and promising in vitro anti-arthritic response were also demonstrated. Moreover, consistent and prolonged in vivo anti-inflammatory effect was achieved, relative to standard AC. Taken together; this study proves the potential of in situ composite gel as an appropriate therapeutic proposal for AC buccal delivery. Graphical Abstract
The Value of Teledermoscopy to the Expertise of General Practitioners Diagnosing Skin Disorders Based on ICD-10 Coding

Early recognition of skin cancer is vital to enhance patient outcomes. Teledermoscopy (TDsc), a telemedicine service, supports general practitioners (GPs) in gaining fast access to dermatologists' feedback to detect skin cancer. This study aimed to assess if GPs gain expertise in diagnosing skin disorders after continued use of TDsc, based on diagnosis classification by the International Statistical Classification of Diseases and Related Health Problems (ICD-10). A retrospective study was conducted on TDsc consultations sent by GPs to teledermatologists in the Netherlands (July 2015 - June 2018). GP sensitivity and confirmed cases in diagnosing skin disorders slightly increased over time. However, the total positive predictive value showed a decrease. In three years, 43 melanomas were diagnosed by the TD for which the GP did not provide a (correct) pre-diagnose. Though GPs appear to improve their expertise in skin disorder detection after continued TDsc use, TDsc remains imperative to early melanoma detection.
Reactive microglia and astrocytes in neonatal intraventricular hemorrhage model are blocked by mesenchymal stem cells

Severe intraventricular hemorrhage (IVH) in premature infants triggers reactive gliosis, causing acute neuronal death and glial scar formation. Transplantation of mesenchymal stem cells (MSCs) has often showed improved CNS recovery in an IVH model, but whether this response is related to reactive glial cells is still unclear. Herein, we suggest that MSCs impede the response of reactive microglia rather than astrocytes, thereby blocking neuronal damage. Astrocytes alone showed mild reactiveness under hemorrhagic conditions mimicked by thrombin treatment, and this was not blocked by MSC‐conditioned medium (MSC‐CM) in vitro. In contrast, thrombin‐induced microglial activation and release of proinflammatory cytokines were inhibited by MSC‐CM. Interestingly, astrocytes showed greater reactive response when co‐cultured with microglia, and this was abolished in the presence of MSC‐CM. Gene expression profiles in microglia revealed that transcript levels of genes for immune response and proinflammatory cytokines were altered by thrombin treatment. This result coincided with the robust phosphorylation of STAT1 and p38 MAPK, which might be responsible for the production and release of proinflammatory cytokines. Furthermore, application of MSC‐CM diminished thrombin‐mediated phosphorylation of STAT1 and p38 MAPK, supporting the acute anti‐inflammatory role of MSCs under hemorrhagic conditions. In line with this, activation of microglia and consequent cytokine release were impaired in Stat1‐null mice. However, reactive response in Stat1‐deficient astrocytes was maintained. Taken together, our results demonstrate that MSCs mainly block the activation of microglia involving STAT1‐mediated cytokine release and subsequent reduction of reactive astrocytes.
Post-vaccination campaign coverage evaluation of oral cholera vaccine, oral polio vaccine and measles–rubella vaccine among Forcibly Displaced Myanmar Nationals in Bangladesh

ABSTRACT Background: The new influx of Forcibly Displaced Myanmar Nationals (FDMNs) into Bangladesh started in August 2017 through different entry points of Bangladesh. Considering the imminent threat of infectious diseases outbreaks, the Government of Bangladesh (GoB) decided to vaccinate children against three deadly diseases (measles, rubella and poliomyelitis) and oral cholera vaccine (OCV) for all except <1 year children. After completion of the campaigns, post-vaccination campaign evaluation was carried out to assess the coverage of OCV, OPV and MR vaccines during campaigns. Methods: Post-vaccination campaign evaluation was conducted after completion of the 2nd dose of oral cholera vaccine (OCV2) and oral polio vaccine (OPV2) through a cross-sectional survey. The evaluation was conducted in the Balukhali camps under Ukhiya upazilla. Precision-based sample size was calculated to estimate the vaccine coverage. Ninety-two trained interviewers were involved to collect data from the target of approximately 40000 FDMNs between 18 and 25 November 2017. Results: Data were collected from 39,438 FDMNs during the survey period. The highest coverage was observed for OCVs (94% for OCV1 and 92% for OCV2). On the other hand, lower coverage was observed for the other vaccines; the coverage for OPV1, OPV2 and MR were 75%, 88% and 38%, respectively. Unawareness (30.7% did not know about the campaign) was the most notable cause of lowering down MR vaccine coverage. Conclusion: The experience in Bangladesh demonstrates that vaccine campaigns can be successfully implemented as part of a comprehensive response toward disease outbreak among high-risk populations in humanitarian crisis.
Airway epithelium-shifted mast cell infiltration regulates asthmatic inflammation via IL-33 signaling.

Asthma is a heterogeneous syndrome that has been subdivided into physiological phenotypes and molecular endotypes. The most specific phenotypic manifestation of asthma is indirect airway hyperresponsiveness (AHR), and a prominent molecular endotype is the presence of type-2 inflammation. The underlying basis for type-2 inflammation and its relationship to AHR are incompletely understood. We assessed the expression of type-2 cytokines in the airways of subjects with and without asthma who were extensively characterized for AHR. Using quantitative morphometry of the airway wall, we identified a shift in mast cells from the submucosa to the airway epithelium specifically associated with both type-2 inflammation and indirect AHR. Using ex vivo modeling of primary airway epithelial cells in organotypic co-culture with mast cells, we have shown that epithelial-derived IL-33 uniquely induced type-2 cytokines in mast cells, which regulated the expression of epithelial IL33 in a feedforward loop. This feedforward loop was accentuated in epithelial cells derived from subjects with asthma. These results demonstrate that type-2 inflammation and indirect AHR in asthma are related to a shift in mast cell infiltration to the airway epithelium, and that mast cells cooperate with epithelial cells through IL-33 signaling to regulate type-2 inflammation.
The role of the 17q21 genotype in the prevention of early childhood asthma and recurrent wheeze by vitamin D

Evidence suggests vitamin D has preventive potential in asthma; however, not all children benefit from this intervention. This study aimed to investigate whether variation in the functional 17q21 single nucleotide polymorphism rs12936231 affects the preventive potential of vitamin D against asthma. A combined secondary analysis of two randomised controlled trials of prenatal vitamin D supplementation for the prevention of asthma in offspring (Vitamin D Antenatal Asthma Reduction Trial (VDAART) and Copenhagen Prospective Studies on Asthma in Childhood 2010 (COPSAC2010)) was performed, stratifying by genotype and integrating metabolite data to explore underlying mechanisms. The protective effect of vitamin D on asthma/wheeze was evident among children with the low-risk rs12936231 GG genotype (hazard ratio (HR) 0.49, 95% CI 0.26–0.94, p=0.032) but not the high-risk CC genotype (HR 1.08, 95% CI 0.69–1.69, p=0.751). In VDAART, in the GG genotype vitamin D supplementation was associated with increased plasma levels of sphingolipids, including sphingosine-1-phosphate (β 0.022, 95% CI 0.001–0.044, p=0.038), but this was not evident with the CC genotype, known to be associated with increased expression of ORMDL3 in bronchial epithelial cells. Sphingolipid levels were associated with decreased risk of asthma/wheeze, and there was evidence of interactions between sphingolipid levels, vitamin D and genotype (p-interactionvitaminD*genotype*sphingosine-1-phosphate=0.035). In a cellular model, there was a significant difference in the induction of sphingosine-1-phosphate by vitamin D between a control human bronchial epithelial cell line and a cell line overexpressing ORMDL3 (p=0.002). Results suggest prenatal vitamin D supplementation may reduce the risk of early childhood asthma/wheeze via alterations of sphingolipid metabolism dependent on the 17q21 genotype. Genetic variation in the 17q21 locus and vitamin D play a role in asthma risk and, as demonstrated for the first time in a human population, sphingolipid biosynthesis may partially underlie these relationships http://bit.ly/2ZbIpsp
Curcumin Acts as a Chemosensitizer for Leiomyosarcoma Cells In Vitro But Fails to Mediate Antioxidant Enzyme Activity in Cisplatin-Induced Experimental Nephrotoxicity in Rats

Background. Cisplatin (cis-diamminedichloroplatinum) is a widely used chemotherapeutic agent for the treatment of various cancers. Although it represents an effective regimen, its application is accompanied by side effects to normal tissues, especially to the kidneys. Cisplatin generates free radicals and impairs the function of antioxidant enzymes. Modulation of cisplatin-induced oxidative stress by specific antioxidant molecules represents an attractive approach to minimize side effects. Methods. We studied the ability of curcumin to sensitize leiomyosarcoma (LMS) cells to cisplatin. Assays for cell proliferation, mitochondrial function, induction of apoptosis, and cell cycle arrest were performed using various concentrations of cisplatin and a concentration of curcumin that caused a nonsignificant reduction in cell viability. Moreover, the effect of curcumin was examined against cisplatin-induced experimental nephrotoxicity. Renal injury was assessed by measuring serum creatinine, blood urea nitrogen (BUN), and the kidney’s relative weight. Oxidative stress was measured by means of enzymatic activities of superoxide dismutase and glutathione peroxidase in the rats’ blood and malondialdehyde levels in rats’ urine. Results. In our study, we found that curcumin sensitizes LMS cells to cisplatin by enhancing apoptosis and impairing mitochondrial function. In an in vivo model of cisplatin-induced experimental nephrotoxicity, intraperitoneal administration of curcumin failed to preserve blood’s antioxidant enzyme activity and decrease lipid peroxidation. Nevertheless, curcumin was able to protect nephrons’ histology from cisplatin’s toxic effect. Conclusion. Our results showed that curcumin can act as chemosensitizer, but its role as an adjunctive cisplatin-induced oxidative stress inhibitor requires further dose-finding studies to maximize the effectiveness of chemotherapy.
Effects of Computerized Guideline-Oriented Clinical Decision Support System on Antithrombotic Therapy in Patients with Atrial Fibrillation: A Systematic Review and Meta-Analysis

A systematic review and meta-analysis was conducted to investigate the effects of computerized guideline-oriented clinical decision support system (CDSS) on antithrombotic therapy in patients with atrial fibrillation. PubMed, the Cochrane Library, and Web of Science were queried. Four studies were included in this meta-analysis. The proportion of appropriate antithrombotic therapy in accordance with clinical guidelines was significantly higher in the CDSS group than in the control group (risk ratio (RR): 1.03, 95% confidence interval (CI): 1.01 to 1.04, P = 0.004). Although the incidence of thromboembolic events was similar between the two groups (RR: 1.12, 95% CI: 0.88 to 1.42, P = 0.357), the incidence of major bleeding tended to be lower in the CDSS group compared with the control group (RR: 0.79, 95% CI: 0.61 to 1.01, P = 0.063). Computerized guideline-oriented CDSS may be effective for appropriate antithrombotic therapy as compared with control in patients with atrial fibrillation.
Hypoxia Has a Lasting Effect on Fast-Startle Behavior of the Tropical Fish Haemulon plumieri

Anthropogenic activities and climate change have resulted in an increase of hypoxic conditions in nearshore ecosystems worldwide. Depending on the persistence of a hypoxic event, the survival of aquatic animals can be compromised. Temperate fish exposed to hypoxia display a reduction in the probability of eliciting startle responses thought to be important for escape from predation. Here we examine the effect of hypoxia on the probability of eliciting fast-startle responses (fast-starts) of a tropical fish, the white grunt (Haemulon plumieri), and whether hypoxia has a prolonged impact on behavior once the fish are returned to normoxic conditions. White grunts collected from the San Juan Bay Estuary in Puerto Rico were exposed to an oxygen concentration of 2.5 mg L−1 (40% dissolved oxygen). We found a significant reduction in auditory-evoked fast-starts that lasted for at least 24 hours after fish were returned to normoxic conditions. Accessibility to the neuronal networks that underlie startle responses was an important motivator for this study. Mauthner cells are identifiable neurons found in most fish and amphibians, and these cells are known to initiate fast-starts in teleost fishes. The assumption that most of the short-latency responses in this study are Mauthner cell initiated provided the impetus to characterize the white grunt Mauthner cell. The identification of the cell provides a first step in understanding how low oxygen levels may impact a single cell and its circuit and the behavior it initiates.