Miracle-dz/UniFAR-FTUs huggingface dataset:
Influence of miR-34a on cerebral neuronal apoptosis in rats with cerebral ischemia reperfusion through the Notch1 signaling pathway.

OBJECTIVE To explore the influence and the underlying mechanism of micro-ribonucleic acid (miR)-34a on cerebral neuronal apoptosis in rats with cerebral ischemia-reperfusion (CIR). MATERIALS AND METHODS 60 adult male Wistar rats were randomly divided into 3 groups: Sham group, CIR group and miR-34a knockdown group. The rat model of CIR was established using the suture occlusion method. The expression level of miR-34a in lesion tissues in the three groups was determined via Reverse Transcription-Polymerase Chain Reaction (RT-PCR). The pathological injury of brain tissues was detected via hematoxylin-eosin (HE) staining and the infarction region in each group was evaluated via triphenyl tetrazolium chloride (TTC) staining. The terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining was performed to measure the cerebral neuronal apoptosis level. The level of Nissl's body in each group was detected via Nissl's staining. The expression level of the platelet-derived neurotrophic factor (PDNF) and Notch1/hypoxia-inducible factor-1α (HIF-1α) signaling pathway-related proteins in brain tissues were detected via immunohistochemistry and Western blotting, respectively. RESULTS The expression level of miR-34a in brain tissues of the CIR group was significantly increased compared to that of the Sham group (p < 0.05). After the intervention with miR-34a, the infarction area of brain tissues was markedly reduced when comparing to the CIR group (p < 0.05). In addition, the results of HE staining and Nissl staining revealed that CIR treatment led to edema in cerebral neurons, disorderly arranged neurons, and remarkably decreased number of Nissl's bodies. However, miR-34a knockdown following CIR significantly alleviated the brain tissue injury and markedly increased the number of Nissl's bodies (p < 0.05). The results of TUNEL staining also indicated that miR-34a siRNA could remarkably reverse the cerebral neuronal apoptosis caused by CIR in rats (p < 0.05). According to the immunohistochemical staining results, the expression of PDNF in brain tissues declined in the CIR group, while enhanced in the miR-34a siRNA group (p < 0.05). Furthermore, the Western blotting results manifested that miR-34a siRNA could up-regulate the Notch1 and HIF-1α protein expressions in brain tissues of CIR rats. CONCLUSIONS Our data demonstrated that the miR-34a knockdown could alleviate the brain tissue injury and neuronal apoptosis by activating the Notch1/HIF-1α signaling pathway CIR-treated rats.
Elevated Endogenous SDHA Drives Pathological Metabolism in Highly Metastatic Uveal Melanoma

Purpose Metastatic uveal melanoma (UM) has a very poor prognosis and no effective therapy. Despite remarkable advances in treatment of cutaneous melanoma, UM remains recalcitrant to chemotherapy, small-molecule kinase inhibitors, and immune-based therapy. Methods We assessed two sets of oxidative phosphorylation (OxPhos) genes within 9858 tumors across 31 cancer types. An OxPhos inhibitor was used to characterize differential metabolic programming of highly metastatic monosomy 3 (M3) UM. Seahorse analysis and global metabolomics profiling were done to identify metabolic vulnerabilities. Analyses of UM TCGA data set were performed to determine expressions of key OxPhos effectors in M3 and non-M3 UM. We used targeted knockdown of succinate dehydrogenase A (SDHA) to determine the role of SDHA in M3 UM in conferring resistance to OxPhos inhibition. Results We identified UM to have among the highest median OxPhos levels and showed that M3 UM exhibits a distinct metabolic profile. M3 UM shows markedly low succinate levels and has highly increased levels of SDHA, the enzyme that couples the tricarboxylic acid cycle with OxPhos by oxidizing (lowering) succinate. We showed that SDHA-high M3 UM have elevated expression of key OxPhos molecules, exhibit abundant mitochondrial reserve respiratory capacity, and are resistant to OxPhos antagonism, which can be reversed by SDHA knockdown. Conclusions Our study has identified a critical metabolic program within poor prognostic M3 UM. In addition to the heightened mitochondrial functional capacity due to elevated SDHA, M3 UM SDHA-high mediate resistance to therapy that is reversible with targeted treatment.
sRNA OsiA Stabilizes Catalase mRNA during Oxidative Stress Response of Deincoccus radiodurans R1

Deinococcus radiodurans adapts to challenging environments by modulating gene expression in response to oxidative stress. Recently, bacterial small noncoding RNAs (sRNAs) have been presumed to participate in the transcriptional or translational regulation of stress-responsive genes. We found 24 sRNAs that may be involved in the oxidative stress response of D. radiodurans by deep RNA sequencing. Moreover, a typical stress-inducible sRNA, IGR_3053, named OsiA, was predicted to bind to the mRNA of katA, katE, and sodC by the bioinformatics method. An osiA knockout of D. radiodurans displayed increased sensitivity to H2O2 and the decreased catalase activity and total antioxidant activity, suggesting that OsiA probably serves as a regulator in the adaptation to oxidative environments. Further microscale thermophoresis results demonstrated that OsiA can directly bind to the mRNA of katA, sodC, and katE. The stability test result of katA mRNA showed that its half-life was 2 min in the osiA mutant compared with 5 min in the wildtype(wt) strain. Our results indicated that OsiA can enhance the stability of katA mRNA and the activity of KatA and consequently the oxidation resistance of D.radiodurans. We are the first one to explore the super-strong oxidative stress resistance of D.radiodurans at the level of post-transcriptional regulation, and found a new pathway that provides a new explanation for the long-term adaptability of D.radiodurans in extreme environments.
Improving the Health of Individuals With Cerebral Palsy: Protocol for the Multidisciplinary Research Program MOVING ON WITH CP

Background Cerebral palsy (CP) is one of the most common early onset disabilities globally. The causative brain damage in CP is nonprogressive, yet secondary conditions develop and worsen over time. Individuals with CP in Sweden and most of the Nordic countries are systematically followed in the national registry and follow-up program entitled the Cerebral Palsy Follow-Up Program (CPUP). CPUP has improved certain aspects of health care for individuals with CP and strengthened collaboration among professionals. However, there are still issues to resolve regarding health care for this specific population. Objective The overall objectives of the research program MOVING ON WITH CP are to (1) improve the health care processes and delivery models; (2) develop, implement, and evaluate real-life solutions for Swedish health care provision; and (3) evaluate existing health care and social insurance benefit programs and processes in the context of CP. Methods MOVING ON WITH CP comprises 9 projects within 3 themes. Evaluation of Existing Health Care (Theme A) consists of registry studies where data from CPUP will be merged with national official health databases, complemented by survey and interview data. In Equality in Health Care and Social Insurance (Theme B), mixed methods studies and registry studies will be complemented with focus group interviews to inform the development of new processes to apply for benefits. In New Solutions and Processes in Health Care Provision (Theme C), an eHealth (electronic health) procedure will be developed and tested to facilitate access to specialized health care, and equipment that improves the assessment of movement activity in individuals with CP will be developed. Results The individual projects are currently being planned and will begin shortly. Feedback from users has been integrated. Ethics board approvals have been obtained. Conclusions In this 6-year multidisciplinary program, professionals from the fields of medicine, social sciences, health sciences, and engineering, in collaboration with individuals with CP and their families, will evaluate existing health care, create conditions for a more equal health care, and develop new technologies to improve the health care management of people with CP. International Registered Report Identifier (IRRID) DERR1-10.2196/13883
Survival Outcomes After Heart Transplantation: Does Recipient Sex Matter?

BACKGROUND Currently, women represent <25% of heart transplant recipients. Reasons for this female underrepresentation have been attributed to selection and referral bias and potentially poorer outcomes in female recipients. The aim of this study was to compare long-term posttransplant survival between men and women, when matched for recipient and donor characteristics. METHODS AND RESULTS Using the International Society for Heart and Lung Transplantation Registry, we performed descriptive analyses and estimated overall freedom from posttransplant death stratified by sex using Kaplan-Meier survival methods. Male and female recipients were matched according to the Index for Mortality Prediction After Cardiac Transplantation and Donor Risk Index score using 1:1 propensity score matching. The study cohort comprised 34 198 heart transplant recipients (76.3% men, 23.7% women) between 2004 and 2014. Compared with men, women were more likely younger (51 [39-59] versus 55 [46-61] years; P<0.001) and had a different distribution of heart failure etiology (P<0.001). In general, the prevalence of comorbidities was lower in women than in men. Women were less likely to have diabetes mellitus (19.1% versus 26.2%; P<0.001), hypertension (40.7% versus 47.9%; P<0.001), peripheral vascular disease (2.4% versus 3.3%; P=0.002), tobacco use (36.5% versus 52.3%; P<0.001), and prior cardiovascular surgery (38.6% versus 50.7%; P<0.001). Women were more likely to have a history of malignancy (10.5% versus 5.3%; P<0.001), require intravenous inotropes (41.4% versus 37.2%; P<0.001), and were less likely supported by an intra-aortic balloon pump (3.3% versus 3.8%; P=0.03) or durable ventricular assist device (22% versus 31.5%; P<0.001). Transplanted male recipients had a higher Index for Mortality Prediction After Cardiac Transplantation score (5 [2-7] versus 4 [1-6]; P<0.001). When male and female heart transplant recipients were matched for recipient and donor characteristics, there was no significant survival difference (P=0.57). CONCLUSIONS Overall survival does not differ between men and women after cardiac transplantation. Women who survive to heart transplantation appear to have lower risk features than male recipients but receive hearts from higher risk donors.
Comparison of analgesic effects of intravenous and intranasal ketorolac in patients with mandibular fracture-A Randomized Clinical Trial

Background Similarity of pharmacokinetics of intranasal ketorolac to the intravenous form and other advantages have promoted its application. This study compared the analgesic effects of intravenous and intranasal ketorolac in patients undergoing mandibular fracture surgery. Material and Methods In this clinical trial study, Sixty-four patients with unilateral mandibular fracture were divided randomly into two groups. In group 1, 30 mg of intravenous (IV) ketorolac was injected every 8 hours and in group 2, intranasal (IN) ketorolac spray was used as a 100-µL puff in each nostril (31.5 mg) every 6 hours. After each patient regained consciousness, pain intensity was measured based on visual analogue scale for 48 hours. Finally, the total dose of the opioid analgesic agent (pethidine) and the time for the first request for an analgesic agent were recorded for each patient, and their means were compared in each group with proper statistical tests. Results Mean pain intensity of patients at baseline was significantly higher than that at other intervals and then, it decreased significantly (P<0.001). Furthermore, 2, 4, 6 and 8 hours after surgery, mean pain intensity in the IN group was significantly lower than that in the IV group (P<0.05). In the IN group, dose of antinociceptive medicine was slightly higher and the time to request it was shorter than the other group, but it was not statistically significant (P >0.05). Conclusions Application of intranasal ketorolac spray decreased pain after mandibular fracture surgery, especially at 8-hour interval after surgery, decreasing the need for opioids. Key words:Ketorolac, intranasal, intravenous, mandibular fracture.
High precision protein functional site detection using 3D convolutional neural networks

Abstract Motivation Accurate annotation of protein functions is fundamental for understanding molecular and cellular physiology. Data-driven methods hold promise for systematically deriving rules underlying the relationship between protein structure and function. However, the choice of protein structural representation is critical. Pre-defined biochemical features emphasize certain aspects of protein properties while ignoring others, and therefore may fail to capture critical information in complex protein sites. Results In this paper, we present a general framework that applies 3D convolutional neural networks (3DCNNs) to structure-based protein functional site detection. The framework can extract task-dependent features automatically from the raw atom distributions. We benchmarked our method against other methods and demonstrate better or comparable performance for site detection. Our deep 3DCNNs achieved an average recall of 0.955 at a precision threshold of 0.99 on PROSITE families, detected 98.89 and 92.88% of nitric oxide synthase and TRYPSIN-like enzyme sites in Catalytic Site Atlas, and showed good performance on challenging cases where sequence motifs are absent but a function is known to exist. Finally, we inspected the individual contributions of each atom to the classification decisions and show that our models successfully recapitulate known 3D features within protein functional sites. Availability and implementation The 3DCNN models described in this paper are available at https://simtk.org/projects/fscnn. Supplementary information Supplementary data are available at Bioinformatics online.
The PEAK family of pseudokinases, their role in cell signalling and cancer

The study of pseudokinases has uncovered that catalysis‐independent functions play a critical role in cell signalling regulation. However, how pseudokinases dynamically assemble and regulate oncogenic signalling pathways remains, in most cases, unclear due to a limited knowledge of the structural determinants that are critical for their functions. Here, we review the recent progress made to unravel the role of the PEAK family of pseudokinases, which comprises SgK269, SgK223 and the recently identified PEAK3, in assembling specific oncogenic signalling pathways that contribute to the progression of several aggressive cancers. We focus on recent structural advances revealing that SgK269 and SgK223 can homo‐ and heteroassociate via a unique dimerisation domain, comprising conserved regulatory helices directly surrounding the pseudokinase domain, which is also conserved in PEAK3. We also highlight a potential oligomerisation mechanism driven by the pseudokinase domain. While it is likely that homo‐ or heterodimerisation and oligomerisation mechanisms contribute to the assembly of complex signalling hubs and provide a means to spatially and temporally modulate and diversify signalling outputs, the exact role that these oncogenic scaffolds play in regulating cell migration, invasion and morphology remains unclear. Here, we attempt to link their structural characteristics to their cellular functions by providing a thorough analysis of the signalling transduction pathways they are known to modulate.
Epidemiology and mortality in bacterial bloodstream infections in patients with hematologic malignancies.

INTRODUCTION Patients with hematological malignancies, who are in the high risk group for infectious complications and bacterial bloodstream infections. The aim of the study evaluated epidemiology and mortality in bacterial bloodstream infections in patients with hematologic malignancies. In addition to determine the risk factors, changes in the distribution and frequency of isolated bacterias. METHODOLOGY In this retrospective study. There were investigated data from 266 patients with hematological malignancies and bacterial bloodstream infections who were hospitalized between the dates 01/01/2012 and 12/31/2017. RESULTS There were 305 blood and catheter cultures in febrile neutropenia attacks in total. In these total attacks, primary bloodstream infections were 166 and catheter-related bloodstream infections were 139. In blood cultures; Escherichia coli and Klebsiella pneumoniae bacteria were detected in 58,0% and 22,9% of the samples, respectively. 52,4% of the cultured Gram-negative bacterias were extended spectrum beta-lactamase (ESBL). Carbapenemase positive culture rate was 17,2% in Gram-negative bacteria cultures. Staphylococcus epidermidis was found in 38,4% of the Gram-positive bacteria cultures. In Gram-positive bacteria; methicillin resistance were detected in 82,2% of the samples. There was a statistically significant relationship between bloodstream infection and disease status. 60 patients with primary bloodstream infections were newly diagnosed. CONCLUSIONS In patients with hematological malignancies, certain factors in the bloodstream infections increase the mortality rate. With the correction of these factors, the mortality rate in these patients can be reduced. The classification of such risk factors may be an important strategy to improve clinical decision making in high-risk patients, such as patients with hematological malignancies.
Pulpa: Beurteilung von Vitalität und Sensibilität

472 Die korrekte Diagnose des Status der Pulpa vor vitalerhaltenden Maßnahmen spielt eine wichtige Rolle für den Therapieerfolg, sodass eine Beurteilung ihres Infektionsund Entzündungsgrads erforderlich ist. Im klinischen Alltag werden Sensibilitätstests genutzt, die einen Rückschluss auf die Vitalität des untersuchten Zahns zulassen. Nur mit angemessenem Kenntnisstand, Fähigkeiten und Materialien können die Zähne möglichst lange erhalten werden.
Uses and Gratifications of Pokémon Go: Why do People Play Mobile Location-Based Augmented Reality Games?

ABSTRACT In recent years, augmented reality games (ARGs) such as Pokémon Go have become increasingly popular. These games not only afford a novel gaming experience but also have the potential to alter how players view their physical realities. In addition to the common experiences and gratifications people derive from games, (location-based) ARGs can afford, for example outdoor adventures, communal activities, and health benefits, but also create problems stemming from, for example privacy concerns and poor usability. This raises some important research questions as to what drives people to use these new applications, and why they may be willing to spend money on the content sold within them. In this study, we investigate the various gratifications people derive from ARGs (Pokémon Go) and the relationship of these gratifications with the players’ intentions to continue playing and spending money on them. We employ data drawn from players of Pokémon Go (N = 1190) gathered through an online survey. The results indicate that game enjoyment, outdoor activity, ease of use, challenge, and nostalgia are positively associated with intentions to reuse (ITR), meanwhile outdoor activity, challenge, competition, socializing, nostalgia and ITR are associated with in-app purchase intentions (IPI). In contrast with our expectations, privacy concerns or trendiness were not associated with reuse intentions or IPI.
Right-time Path Switching Method for Proxy Mobile IPv6 Route Optimization

—Proxy Mobile IPv6 provides IP mobility to a mobile node by the proxy mobility agent called a Local Mobility Anchor and a Mobile Access Gateway without requiring mobile node’s participation in any mobility-related signaling. Increased demand for content-rich mobile data communications is prompting mobile network operators to deploy efficient mobility management including Proxy Mobile IPv6. The route optimization technique is applied to the data path between mobile nodes in the same Proxy Mobile IPv6 domain by bypassing the Local Mobility Anchor(s). However, when switching the data path from the default (non-optimized) route to an optimized one, the delay gap between these paths leads to performance degradation due to out-of-sequence packets, or unnecessary communication disruption. We propose a right-time path switching method for Proxy Mobile IPv6 route optimization. This method enables the Mobile Access Gateway to switch these paths with the accurate timing provided by the designated signaling messages, which prevents out-of-sequence packets as well as minimizing communication disruption during the route optimization procedure. The proposed method is evaluated in an actual testbed to show that the proposed method achieves the seamless path switch.
DNMIVD: DNA methylation interactive visualization database

Abstract Aberrant DNA methylation plays an important role in cancer progression. However, no resource has been available that comprehensively provides DNA methylation-based diagnostic and prognostic models, expression–methylation quantitative trait loci (emQTL), pathway activity-methylation quantitative trait loci (pathway-meQTL), differentially variable and differentially methylated CpGs, and survival analysis, as well as functional epigenetic modules for different cancers. These provide valuable information for researchers to explore DNA methylation profiles from different aspects in cancer. To this end, we constructed a user-friendly database named DNA Methylation Interactive Visualization Database (DNMIVD), which comprehensively provides the following important resources: (i) diagnostic and prognostic models based on DNA methylation for multiple cancer types of The Cancer Genome Atlas (TCGA); (ii) meQTL, emQTL and pathway-meQTL for diverse cancers; (iii) Functional Epigenetic Modules (FEM) constructed from Protein-Protein Interactions (PPI) and Co-Occurrence and Mutual Exclusive (COME) network by integrating DNA methylation and gene expression data of TCGA cancers; (iv) differentially variable and differentially methylated CpGs and differentially methylated genes as well as related enhancer information; (v) correlations between methylation of gene promoter and corresponding gene expression and (vi) patient survival-associated CpGs and genes with different endpoints. DNMIVD is freely available at http://www.unimd. org/dnmivd/. We believe that DNMIVD can facilitate research of diverse cancers.