Miracle-dz/UniFAR-FTUs huggingface dataset:
Application of policy analysis frameworks in tobacco control research: A systematic review of qualitative literature

Background: Tobacco consumption is still considered as the first preventable cause of death in the world. In order to influence tobacco policy process, researchers and policymakers must use frameworks of policy-making to understand the process to provide them insights for influence the process. This systematic review aims to review the application of policy analysis frameworks in the field of tobacco control. Methods: A systematic search for articles was performed using four databases (Ovid Medline, Scopus, Cochrane Library, and PubMed) up to December 19, 2016. The articles were selected based on inclusion and exclusion criteria. All research studies focusing on tobacco policy and on one or more specified frameworks of policy analysis included in this study. Finally, thematic analysis was used to synthesize the findings. Results: 17 studies based on eligibility criteria were included in this study. The findings of this study showed that most of the studies were in North America, published in the Health journals, conducted to analyze the national and state policies, focused on analyzing agenda-setting phase. Multiple streams model was the most widely used framework within the literature. Few studies had used advocacy coalition framework. From the three agenda setting frameworks and theories (MSF, PEF, ACF), the ACF framework is the most detailed framework in terms of elements and factors affecting the dynamics of political sub-system the reasons for models selection and suitability for the study was noted only in a small number of studies. The results of this study showed underuse and the incomplete or improper use of policy analysis models and frameworks in the field of tobacco research. Conclusion: The study showed that a number of theories and frameworks have been used but their use was limited and have significant methodological weaknesses.
Kidney size in relation to ageing, gender, renal function, birthweight and chronic kidney disease risk factors in a general population.

Background The relationship of kidney size to ageing, kidney function and kidney disease risk factors is not fully understood. Methods Ultrasound length and parenchymal kidney volume were determined from a population-based sample of 3972 Sardinians (age range 18-100 years). We then identified the subset of 2256 'healthy' subjects to define age- and sex-specific reference ranges (2.5-97.5 percentile) of kidney volume. Logistic regression (accounting for family clustering) was used to identify the clinical characteristics associated with abnormally large kidneys or abnormally small kidneys. Results In the healthy subset, kidney volume and length increased up to the fourth to fifth decade of life followed by a progressive decrease in men, whereas there was a gradual kidney volume decrease throughout the lifespan of women. In the whole sample, independent predictors of lower kidney volume (<2.5 percentile for age and sex) were male sex, low body mass index, short height, low waist:hip ratio and high serum creatinine (SCr); the independent predictors of larger kidney volume (>97.5 percentile for age and sex) were younger age, female sex, diabetes, obesity, high height, high waist:hip ratio and lower SCr. Estimated heritability for kidney volume was 15%, and for length 27%; kidney volume correlated strongly with birthweight. Conclusions Overall, in a general healthy population, kidney measures declined with age differently in men and women. The determinants of kidney parenchymal volume include genetic factors and modifiable clinical factors.
Sarcoglycan Alpha Mitigates Neuromuscular Junction Decline in Aged Mice by Stabilizing LRP4

During aging, acetylcholine receptor (AChR) clusters become fragmented and denervated at the neuromuscular junction (NMJ). Underpinning molecular mechanisms are not well understood. We showed that LRP4, a receptor for agrin and critical for NMJ formation and maintenance, was reduced at protein level in aged mice, which was associated with decreased MuSK tyrosine phosphorylation, suggesting compromised agrin-LRP4-MuSK signaling in aged muscles. Transgenic expression of LRP4 in muscles alleviated AChR fragmentation and denervation and improved neuromuscular transmission in aged mice. LRP4 ubiquitination was augmented in aged muscles, suggesting increased LRP4 degradation as a mechanism for reduced LRP4. We found that sarcoglycan α (SGα) interacted with LRP4 and delayed LRP4 degradation in cotransfected cells. AAV9-mediated expression of SGα in muscles mitigated AChR fragmentation and denervation and improved neuromuscular transmission in aged mice. These observations support a model where compromised agrin-LRP4-MuSK signaling serves as a pathological mechanism of age-related NMJ decline and identify a novel function of SGα in stabilizing LRP4 for NMJ stability in aged mice. SIGNIFICANCE STATEMENT This study provides evidence that LRP4, a receptor of agrin that is critical for NMJ formation and maintenance, is reduced at protein level in aged muscles. Transgenic expression of LRP4 in muscles ameliorates AChR fragmentation and denervation and improves neuromuscular transmission in aged mice, demonstrating a critical role of the agrin-LRP4-MuSK signaling. Our study also reveals a novel function of SGα to prevent LRP4 degradation in aged muscles. Finally, we show that NMJ decline in aged mice can be mitigated by AAV9-mediated expression of SGα in muscles. These observations provide insight into pathological mechanisms of age-related NMJ decline and suggest that improved agrin-LRP4-MuSK signaling may be a target for potential therapeutic intervention.
Regulation of Human Airway Epithelial Tissue Stem Cell Differentiation by β‐Catenin, P300, and CBP

The wingless/integrase‐1 (WNT)/β‐catenin signaling pathway is active in several chronic lung diseases including idiopathic pulmonary fibrosis, asthma, and chronic obstructive pulmonary disease. Although this WNT/β‐catenin pathway activity is associated with an increase in mucus cell frequency and a decrease in ciliated cell frequency, a cause and consequence relationship between signaling and cell frequency has not been established. We previously demonstrated that genetic stabilization of β‐catenin inhibited differentiation of mouse bronchiolar tissue stem cells (TSC). This study determined the effect of β‐catenin and its co‐factors P300 (E1A‐binding protein, 300 kDa) and cAMP response element binding (CREB)‐binding protein (CBP) on human bronchial epithelial TSC differentiation to mucus and ciliated cells. We developed a modified air–liquid interface (ALI) culture system in which mucus and ciliated cell frequency is similar. These cultures were treated with the β‐catenin agonist CHIR99021 (CHIR) and antagonists to β‐catenin (XAV939), P300 (IQ1), and CBP (ICG001). We report that human TSC differentiation to mucus and ciliated cells can be divided into two stages, specification and commitment. CHIR treatment inhibited mucus and ciliated cell commitment while XAV939 treatment demonstrated that β‐catenin was necessary for mucus and ciliated cell specification. Additional studies demonstrate that a β‐catenin/P300 complex promotes mucus cell specification and that β‐catenin interacts with either P300 or CBP to inhibit ciliated cell commitment. These data indicate that activation of β‐catenin‐dependent signaling in chronic lung disease leads to changes in mucus and ciliated cell frequency and that P300 and CBP tune the β‐catenin signal to favor mucus cell differentiation. Stem Cells 2018;36:1905–12
Integrated analysis of a competing endogenous RNA network reveals key lncRNAs as potential prognostic biomarkers for human bladder cancer

Abstract Human bladder cancer (BCa) is one of the most commonly diagnosed malignancies worldwide. It has high recurrence rates and low-grade malignancy, thus representing an important public health concern. An increasing number of studies suggest that long-noncoding RNAs (lncRNAs) play important roles in various biological processes and disease pathologies, including cancer. We analyzed the expression profiles of lncRNA, miRNA, and mRNA, along with the clinical information of BCa patients collected from the Cancer Genome Atlas database to identify lncRNA biomarkers for prognosis. We also constructed an lncRNA–miRNA–mRNA global triple network (competitive endogenous RNA network) by bioinformational approach. This BCa lncRNA–miRNA–mRNA network consisted of 23 miRNA nodes, 52 mRNA nodes, 59 lncRNA nodes, and 365 edges. Subsequent gene ontology (GO) and pathway analyses were performed using BinGO for Cytoscape and Database for Annotation, Visualization, and Integration Discovery, respectively, highlighting important GO terms and pathways that were enriched in the network. Subnetworks were created using 3 key lncRNAs (MAGI2-AS3, ADAMTS9-AS2, and LINC00330), revealing associations with BCa-linked mRNAs and miRNAs. Finally, an analysis of significantly differentiating RNAs found 6 DElncRNAs (AC112721.1, ADAMTS9-AS1, ADAMTS9-AS2, HCG22, MYO16-AS1, and SACS-AS1), 1 DEmiRNA (miRNA-195), and 6 DEmRNAs (CCNB1, FAM129A, MAP1B, TMEM100, AIFM3, and HOXB5) that correlated with BCa patient survival. Our results provide a novel perspective from which to study the lncRNA-related ceRNA network in BCa, contributing to the development of future diagnostic biomarkers and therapeutic targets.
Clinical and molecular characteristics of MEF2D fusion-positive B-cell precursor acute lymphoblastic leukemia in childhood, including a novel translocation resulting in MEF2D-HNRNPH1 gene fusion

Fusion genes involving MEF2D have recently been identified in precursor B-cell acute lymphoblastic leukemia, mutually exclusive of the common risk stratifying genetic abnormalities, although their true incidence and associated clinical characteristics remain unknown. We identified 16 cases of acute lymphoblastic leukemia and 1 of lymphoma harboring MEF2D fusions, including MEF2D-BCL9 (n=10), MEF2D-HNRNPUL1 (n=6), and one novel MEF2D-HNRNPH1 fusion. The incidence of MEF2D fusions overall was 2.4% among consecutive precursor B-cell acute lymphoblastic leukemia patients enrolled onto a single clinical trial. They frequently showed a cytoplasmic μ chain-positive pre-B immunophenotype, and often expressed an aberrant CD5 antigen. Besides up- and down-regulation of HDAC9 and MEF2C, elevated GATA3 expression was also a characteristic feature of MEF2D fusion-positive patients. Mutations of PHF6, recurrent in T-cell acute lymphoblastic leukemia, also showed an unexpectedly high frequency (50%) in these patients. MEF2D fusion-positive patients were older (median age 9 years) with elevated WBC counts (median: 27,300/ml) at presentation and, as a result, were mostly classified as NCI high risk. Although they responded well to steroid treatment, MEF2D fusion-positive patients showed a significantly worse outcome, with 53.3% relapse and subsequent death. Stem cell transplantation was ineffective as salvage therapy. Interestingly, relapse was frequently associated with the presence of CDKN2A/CDKN2B gene deletions. Our observations indicate that MEF2D fusions comprise a distinct subgroup of precursor B-cell acute lymphoblastic leukemia with a characteristic immunophenotype and gene expression signature, associated with distinct clinical features.
Low expression of microRNA‐340 confers adverse clinical outcome in patients with acute myeloid leukemia

MicroRNA‐340 (miR‐340) was considered as a tumor suppressor by affecting cancer cell proliferation, apoptosis, invasion, and migration, and was downregulated in diverse cancers. Moreover, dysregulation of miR‐340 was also found to be associated with drug resistance and predicted patients’ survival in various cancers. Herein, we investigated miR‐340 expression and its clinical significance in acute myeloid leukemia (AML). Real‐time quantitative polymerase chain reaction was performed to detect miR‐340 expression in bone marrow (BM) from 99 newly diagnosed AML patients except for acute promyelocytic leukemia (APL), 19 AML patients achieved complete remission (CR), and 29 healthy donors. BM miR‐340 expression was significantly underexpressed in newly diagnosed AML patients as compared with controls (p = 0.031) and AML patients achieved CR (p = 0.025). No significant differences were observed between miR‐340 expression and most of the clinicopathologic features (p > 0.05). However, low miR‐340 expression was found to be associated with lower CR rate in both non‐APL‐AML and cytogenetically normal AML (CN‐AML; p = 0.001 and 0.031, respectively), and acted as an independent risk factor for CR by logistic regression analysis (p = 0.001 and 0.021, respectively). More important, among both non‐APL‐AML and CN‐AML, low expression of miR‐340 was also associated with shorter overall survival (OS; p = 0.013 and 0.005, respectively), and was further validated by Cox regression (p = 0.031 and 0.039, respectively). Collectively, our study showed that BM miR‐340 expression was downregulated in AML, and low expression of miR‐340 correlated with adverse prognosis.
Understanding the Relationship between Quality and Security: A Large-Scale Analysis of Android Applications

Android applications (apps) are not immune to the problems which also plague conventional software including security vulnerabilities, quality defects, permission misuse, and numerous other issues. Many developers even intentionally create vulnerable or malicious apps (malware) for often highly lucrative purposes. We need to better understand current trends in app quality and security to create higher quality software, and more effectively battle malware. To gather this critical information, we collected and reverse engineered 70,785 Android apps from the Google Play store, along with 1,420 malicious apps from other sources. Each app was analyzed using several static analysis tools to record a variety of information about each of them including requested permissions, size (LOC), possible defects and permission misuse. Our findings conclude that: 1) app categories substantially differ in terms of permissions misuse; 2) at an aggregate level, there is no significant correlation between an app's quality and security; 3) that malware typically requests more permissions and suffers from several quality-related metrics in comparison to benign apps; 4) that malware and benign apps are growing annually both in terms of LOC and requested permissions. We also present an easy to use, robust dataset for the community to replicate or extend this study.
An IoT based monitoring and controlling system for water chlorination treatment

With the recent development of the Internet, the availability of a variety of low cost sensors and the evolution of the Internet of Things (IoT), the development of remote real-time monitoring and controlling systems - without the need of direct human intervention - has expanded significantly in various application domains. The Water sector is one of the most important industrial application domains that demands developing efficient and effective water quality monitoring and control; considering the scarcity of natural water resources worldwide, and in Palestine region in particular. In this research work, we address the problems faced the monitoring and controlling of water chlorination that fully depends on human intervention. In addition, we propose developing an IoT based system prototype that remotely monitors and controls direct water treatment (Chlorination Treatment as a pilot phase) in Water Pumping Stations (WPS). The proposed system monitors the concentration of chlorine and controls the dosing pump to keep chlorine concentration as desired with little as possible human intervention. In addition, it monitors the chlorine level in tanks, and alerts the human operator for immediate actions in abnormal cases. A prototype of the proposed system has been set up to experimental test and validates our proposal.
Stylometric Studies based on Tone and Word Length Motifs

: We propose a new approach to stylometric analysis combining lexical and textual information, but without annotation or other pre-processing. In particular, our study makes use Chinese tones motifs and word length motifs automatically extracted from unannotated texts. The proposed approach is based on linked data in nature as tone and word-length information is extracted from a lexicon and mapped to the text. Support vector machine and random forest were used to establish the classification models for author differentiation. Based on comparative study of classification results of different models, we conclude that the combination of word-final tones motifs, segment-final motifs and word length motifs provides the best outcome and hence is the best model.
Low proportion of unreported cervical treatments in the cancer registry of Norway between 1998 and 2013

Abstract Background: Accurate information about treatment is needed to evaluate cervical cancer prevention efforts. We studied completeness and validity of reporting cervical treatments in the Cancer Registry of Norway (CRN). Material and methods: We identified 47,423 (92%) high-grade cervical dysplasia patients with and 3983 (8%) without recorded treatment in the CRN in 1998–2013. We linked the latter group to the nationwide registry of hospital discharges in 1998–2015. Of patients still without treatment records, we randomly selected 375 for review of their medical history. Factors predicting incomplete treatment records were assessed by multiple imputation and logistic regression. Results: Registry linkage revealed that 10% (401/3983) of patients received treatment, usually conization, within one year of their initial high-grade dysplasia diagnosis. Of those, 11% (n = 44) were missing due to unreporting and 89% (n = 357) due to misclassification at the CRN. Of all cases in medical review, patients under active surveillance contributed almost 60% (223/375). Other reasons of being without recorded treatment were uncertain dysplasia diagnosis, invasive cancer or death. Coding error occurred in 19% (73/375) of randomly selected cases. CRN undercounted receipt of treatment by 38% (n = 1526) among patients without recorded treatment which translates into 97% overall completeness of treatment data. Incomplete treatment records were particularly associated with public laboratories, patients aged 40–54 years, and the latest study years. Conclusions: CRN holds accurate information on cervical treatments. Completeness and particularly validity can be further improved through the establishment of new internal routines and regular linkage to hospital discharges.
Ca2+ Signals in Astrocytes Facilitate Spread of Epileptiform Activity

Abstract Epileptic seizures are associated with increased astrocytic Ca2+ signaling, but the fine spatiotemporal kinetics of the ictal astrocyte–neuron interplay remains elusive. By using 2-photon imaging of awake head-fixed mice with chronic hippocampal windows we demonstrate that astrocytic Ca2+ signals precede neuronal Ca2+ elevations during the initial bout of kainate-induced seizures. On average, astrocytic Ca2+ elevations preceded neuronal activity in CA1 by about 8 s. In subsequent bouts of epileptic seizures, astrocytes and neurons were activated simultaneously. The initial astrocytic Ca2+ elevation was abolished in mice lacking the type 2 inositol-1,4,5-trisphosphate-receptor (Itpr2−/−). Furthermore, we found that Itpr2−/− mice exhibited 60% less epileptiform activity compared with wild-type mice when assessed by telemetric EEG monitoring. In both genotypes we also demonstrate that spreading depression waves may play a part in seizure termination. Our findings imply a role for astrocytic Ca2+ signals in ictogenesis.
Identification of Preoperative Magnetic Resonance Imaging Features Associated with Positive Resection Margins in Breast Cancer: A Retrospective Study

Objective To determine which preoperative breast magnetic resonance imaging (MRI) findings and clinicopathologic features are associated with positive resection margins at the time of breast-conserving surgery (BCS) in patients with breast cancer. Materials and Methods We reviewed preoperative breast MRI and clinicopathologic features of 120 patients (mean age, 53.3 years; age range, 27–79 years) with breast cancer who had undergone BCS in 2015. Tumor size on MRI, multifocality, patterns of enhancing lesions (mass without non-mass enhancement [NME] vs. NME with or without mass), mass characteristics (shape, margin, internal enhancement characteristics), NME (distribution, internal enhancement patterns), and breast parenchymal enhancement (BPE; weak, strong) were analyzed. We also evaluated age, tumor size, histology, lymphovascular invasion, T stage, N stage, and hormonal receptors. Univariate and multivariate logistic regression analyses were used to determine the correlation between clinicopathological features, MRI findings, and positive resection margins. Results In univariate analysis, tumor size on MRI, multifocality, NME with or without mass, and segmental distribution of NME were correlated with positive resection margins. Among the clinicopathological factors, tumor size of the invasive breast cancer and in situ components were significantly correlated with a positive resection margin. Multivariate analysis revealed that NME with or without mass was an independent predictor of positive resection margins (odds ratio [OR] = 7.00; p < 0.001). Strong BPE was a weak predictor of positive resection margins (OR = 2.59; p = 0.076). Conclusion Non-mass enhancement with or without mass is significantly associated with a positive resection margin in patients with breast cancer. In patients with NME, segmental distribution was significantly correlated with positive resection margins.
Right Pretemporal-Transsylvian Approach for Resection of a Midbrain Cavernous Malformation: 3-Dimensional Operative Video.

Brainstem cavernous malformations (CMs) account for 15% to 18% of all intracranial CMs1 and 13% of all cerebrovascular pathology in the posterior fossa.1,2 This video demonstrates the resection of a pontomesencephalic CM through a pretemporal approach through the oculomotor-tentorial triangle (OTT). 3 A 49-yr-old woman presented with an acute onset of left hemiparesis, diplopia, vertigo, partial oculomotor, and facial palsy. Neuroimaging revealed a 25-mm diameter right pontomesencephalic CM with evidence of prior hemorrhage. Institutional Review Board approval and patient consent were obtained for surgery. A right orbitozygomatic craniotomy was performed, and the lesion was exposed through a pretemporal-transsylvian approach. After a wide Sylvian fissure split, the oculomotor nerve (CN III) was dissected away from the temporal lobe, and the temporal lobe was mobilized posteriorly to access the OTT. The posterior cerebral and superior cerebellar arteries were visualized in this triangle, and the cerebral peduncle and the CM were accessed deep to these arteries. After hematoma evacuation, the CM was resected in a piece-meal fashion using an intracapsular technique. Postoperative imaging confirmed the gross total resection of the lesion. The patient had persistent right CN III palsy and a slight worsening of left hemiparesis, which had resolved completely at the 6-mo follow-up. The OTT provides access to the upper ventrolateral pontomesencephalic area.3 This triangular surgical workspace is entered through a pretemporal-transsylvian corridor and widened with posterior temporal lobe retraction. The OTT is an important working space for accessing midbrain and upper pontine CMs posterolateral to CN III.