Miracle-dz/UniFAR-FTUs huggingface dataset:
PTEN Hamartoma Tumor Syndrome: A Clinical Overview

The phosphatase and tensin homolog (PTEN) hamartoma tumor syndrome (PHTS) is a grouping of related genetic disorders that has been linked to germline mutations in the PTEN gene. These disorders include Cowden syndrome (CS), Bannayan–Riley–Ruvalcaba syndrome, adult Lhermitte–Duclos disease, and autism spectrum disorders associated with macrocephaly. The majority of the clinical information available on PHTS, however, is related to individuals diagnosed with CS. There is still much to be learned about this disorder, since diagnostic criteria for CS were only established in 1996, before the identification of the PTEN gene, and were based primarily on features seen in cases reported in the existing literature. More recently, however, data from several large series of patients have shown that a number of the clinical features associated with PTEN mutations are either more or less common than previously reported. In addition, we now know that only about 30–35% of patients meeting clinical diagnostic criteria for Cowden syndrome actually have a detectable PTEN mutation. Thus, our understanding of PTEN-related diseases and their management has evolved significantly over time. The United States National Comprehensive Cancer Network (NCCN) has produced and regularly updates practice guidelines which include clinical diagnostic criteria as well as guidelines for PTEN testing and management of patients with mutations. This review will summarize the overall literature on PHTS as well as recent findings which are broadening our understanding of this set of disorders.
Clinical Impact of the Increase in Immunosuppressive Cell-Related Gene Expression in Urine Sediment during Intravesical Bacillus Calmette-Guérin

Background: The aim of this study is to evaluate the clinical impact of intravesical Bacillus Calmette-Guérin (BCG)-induced changes in blood/urinary immune markers. Methods: Time-course changes in blood/urinary clinical parameters and mRNA expression of 13 genes in urine sediment taken eight times during the treatment course of intravesical BCG (before, every 2 weeks for 8 weeks, and after) in 24 patients with non-muscle invasive bladder cancer. The genes examined include cellular markers of four immune checkpoint proteins (PD-L1, PD-L2, PD-1, and CTLA-4), immunosuppressive cells (regulatory T cells, tumor-associated macrophages, and myeloid-derived suppressor cells), pan-T lymphocytes, B lymphocytes, and neutrophils. Results: Significant transient increase in gene expression was observed for PD-L1, PD-1, FOXP3, and CD204 at 6–8 doses of BCG. The patients were stratified into two groups depending on the number of genes with increased mRNA expression. Fourteen (58%) had 0–1 genes upregulated, while 10 (42%) had 2–4 genes with increased expression. No patient in the 0–1 group experienced recurrence, while 70% of patients in the 2–4 group experienced recurrence (p value = 0.037, hazard ratio = 5.93). Conclusions: Our findings suggested that increases in more than one of PD-L1, PD-1, FOXP3, and CD204, expression in the urine sediments was associated with resistance to BCG treatment.
Engagement in physical activity, suicidal thoughts and suicide attempts among older people in five developing countries

Background Suicide causes rising economic costs and public health risks for communities in the worldwide. Physical activity (PA) is considered a potentially feasible approach to reduce risk of suicide with low cost and high accessibility, and therefore attracting increasing attention. However, current literature on the association between PA and suicidal behavior amongst elderly people in low- and middle-income countries (LMICs) are scarce. Therefore, in this study we aimed to examine the relationship between suicidal thoughts (ST) and suicidal attempts (SA) with PA among elderly people in five LMICs. Methods Cross-sectional data were collected from WHO’s Study of Global Ageing and Adult Health (SAGE) with 2,861 participants aged 50 years or above. Variables included: self-reported occurrence of ST and SA during past 12 months and four types of PA (vigorous physical activity (VPA), moderate physical activity (MPA), walking/bike riding, moderate leisure time physical activity (MLPA)). Results The overall prevalence of taking >75 min of VPA/week, >150 min/week, MLPA and walking/bike riding were, respectively, 85.4% (95% CI [81.3–88.7]), 61.6% (95% CI [52.9–69.6]), 9.6% (95% CI [7.2–12.6]) and 75.1% (95% CI [68.7–80.6]). Respectively, 31.0% (95% CI [24.3–38.7]) and 5.5% (95% CI [3.9–7.5]) of the respondents reported having morbid thoughts and SA during last 12 months. In adjusted multivariable regression analysis, not engaging in PA revealed positive association with higher odds of having morbid thoughts and SA, however, with varying degrees for different types of PA among men and women and across countries. The adjusted odds ratio among elderly who encountered ST increased significantly with PA levels (1.265 in male and 1.509 in female with VPA, 1.292 in male and 1.449 in female with MPA, 1.669 in female with LMPA and 3.039 in women with walk/bike); similarly, with SA (1.526, 1.532, 1.474 and 1.392 in women with VPA, MPA, LMPA and Walk/bike, respectively). The degree of adjusted odds ratio varied between genders and among countries. Conclusion Although the data were cross-sectional, and no linear dose-response relationship was observed between PA and morbid thought and suicide ideation, the findings provide important indications of potential harmful effects of no/inadequate PA on psychological morbidities among older individuals. Promoting adequate PA among older individuals through community-based suicide prevention programs can potentially contribute to reduction in the burden of PA in LMICs.
Characteristics of Breakthrough Pain and Its Impact on Quality of Life in Terminally Ill Cancer Patients

Purpose. This study aimed to characterize breakthrough pain (BTP) and investigate its impact on quality-of-life (QoL) in terminally-ill cancer patients. Similarities and differences between high and low predictable BTP were also tested. Methods. Secondary analysis of a multicenter longitudinal observational study included 92 patients at their end-of-life. BTP was assessed with a short form of the Italian version of the Alberta Breakthrough Pain Assessment Tool. QoL was assessed with the Palliative Outcome Scale (0-40). Patients were stratified by self-reported BTP predictability into unpredictable BTP (never or rarely able to predict BTP) and predictable BTP (sometimes to always able to predict BTP). Results. In all, 665 BTP episodes were recorded (median 0.86 episodes/day). A median duration of 30 minutes and a median peak intensity score of 7 out of 10 were reported. Time to peak was <10 minutes, 10 to 30 minutes, and ≥30 minutes in 267 (41.1%), 259 (39.9%), and 30 (4.6%) of the episodes, respectively. Onset of relief occurred after a median of 30 minutes. Time to peak (P < .001) and duration (P = .046) of BTP was shorter in patients with predictable pain (n = 31), who usually were younger than those with unpredictable pain (P = .03). The mean (SD) QoL score was 14.6 (4.6). No difference in QoL between patients with predictable and unpredictable BTP was found (P = .49). Conclusions. In terminally-ill cancer patients, BTP is a severe problem with a negative impact on QoL and has different characteristics according to its predictability.
Orientation Prior and Consistent Model Selection Increase Sensitivity of Tract-Based Spatial Statistics in Crossing-Fiber Regions

The goal of this paper is to increase the statistical power of crossing-fiber statistics in voxelwise analyses of diffusion-weighted magnetic resonance imaging (DW-MRI) data. In the proposed framework, a fiber orientation atlas and a model complexity atlas were used to fit the ball-and-sticks model to diffusion-weighted images of subjects in a prospective population-based cohort study. Reproducibility and sensitivity of the partial volume fractions in the ball-and-sticks model were analyzed using TBSS (tract-based spatial statistics) and compared to a reference framework. The reproducibility was investigated on two scans of 30 subjects acquired with an interval of approximately three weeks by studying the intraclass correlation coefficient (ICC). The sensitivity to true biological effects was evaluated by studying the regression with age on 500 subjects from 65 to 90 years old. Compared to the reference framework, the ICC improved significantly when using the proposed framework. Higher t-statistics indicated that regression coefficients with age could be determined more precisely with the proposed framework and more voxels correlated significantly with age. The application of a fiber orientation atlas and a model complexity atlas can significantly improve the reproducibility and sensitivity of crossing-fiber statistics in TBSS.
Teaching pronunciation for English as a Lingua Franca: a sociopolitical perspective

The English language is the medium of globalisation and it is itself deeply affected by globalisation. As a result, the function of English as an international tool for communication needs rethinking in the English language classroom. The articles of this volume represent different, sometimes controversial perspectives. The contributions cover five domains: 1. Political and Sociocultural Dimensions, 2. Linguistic and Sociolinguistic Exemplification, 3. Teaching and Learning English in a Global Context: 'Old' and 'New' Standards, 4. Learners in Primary, Secondary and Higher Education: Focus on Europe and 5. Teacher Education. The sections provide different focuses and use different approaches to the globalisation of English and its possible consequences for the language classroom.
Action in auctions: neural and computational mechanisms of bidding behaviour

Competition for resources is a fundamental characteristic of evolution. Auctions have been widely used to model competition of individuals for resources, and bidding behavior plays a major role in social competition. Yet how humans learn to bid efficiently remains an open question. We used model-based neuroimaging to investigate the neural mechanisms of bidding behavior under different types of competition. Twenty-seven subjects (nine male) played a prototypical bidding game: a double action, with three “market” types, which differed in the number of competitors. We compared different computational learning models of bidding: directional learning models (DL), where the model bid is “nudged” depending on whether it was accepted or rejected, along with standard reinforcement learning models (RL). We found that DL fit the behavior best and resulted in higher payoffs. We found the binary learning signal associated with DL to be represented by neural activity in the striatum distinctly posterior to a weaker reward prediction error signal. We posited that DL is an efficient heuristic for valuation when the action (bid) space is continuous. Indeed, we found that the posterior parietal cortex represents the continuous action-space of the task, and the frontopolar prefrontal cortex distinguishes among conditions of social competition. Based on our findings we proposed a conceptual model that accounts for a sequence of processes that are required to perform successful and flexible bidding under different types of competition.
Cross-transmission Is Not the Source of New Mycobacterium abscessus Infections in a Multicenter Cohort of Cystic Fibrosis Patients

Abstract Background Mycobacterium abscessus is an extensively drug–resistant pathogen that causes pulmonary disease, particularly in cystic fibrosis (CF) patients. Identifying direct patient-to-patient transmission of M. abscessus is critically important in directing an infection control policy for the management of risk in CF patients. A variety of clinical labs have used molecular epidemiology to investigate transmission. However, there is still conflicting evidence as to how M. abscessus is acquired and whether cross-transmission occurs. Recently, labs have applied whole-genome sequencing (WGS) to investigate this further and, in this study, we investigated whether WGS can reliably identify cross-transmission in M. abscessus. Methods We retrospectively sequenced the whole genomes of 145 M. abscessus isolates from 62 patients, seen at 4 hospitals in 2 countries over 16 years. Results We have shown that a comparison of a fixed number of core single nucleotide variants alone cannot be used to infer cross-transmission in M. abscessus but does provide enough information to replace multiple existing molecular assays. We detected 1 episode of possible direct patient-to-patient transmission in a sibling pair. We found that patients acquired unique M. abscessus strains even after spending considerable time on the same wards with other M. abscessus–positive patients. Conclusions This novel analysis has demonstrated that the majority of patients in this study have not acquired M. abscessus through direct patient-to-patient transmission or a common reservoir. Tracking transmission using WGS will only realize its full potential with proper environmental screening, as well as patient sampling.
A Validated Questionnaire to Assess the Severity of Persistent Postural-Perceptual Dizziness (PPPD): The Niigata PPPD Questionnaire (NPQ)

Objective: To establish a questionnaire to diagnose and assess the severity of persistent postural-perceptual dizziness (PPPD). Study Design: Retrospective chart review. Setting: Tertiary referral center. Patients: Fifty PPPD patients and 50 consecutive control patients with other vestibular disorders. Interventions: Patients answered questions on three exacerbating factors of PPPD (upright posture/walking, movement, and visual stimulation), and each factor was evaluated using four questions scoring the severity from 0 (none) to 6 (unbearable). Somatic and psychological distress was evaluated by the Visual Analog Scale (VAS) and the Hospital Anxiety and Depression Scale (HADS), respectively. Main Outcome Measures: The questionnaire's reliability was tested by Cronbach's alpha, and it was validated by examining the differences in the questionnaire's scores between PPPD patients and controls. The area under the curve (AUC) of the receiver operating characteristic curve for each factor was calculated. Results: Cronbach's alpha coefficient was >0.8 for all factors, except the movement factor. There were no significant differences in the VAS and HADS scores between the two groups. However, the combined and individual questionnaire scores for each factor were higher in PPPD patients than in controls, indicating the questionnaire's high validity. The AUC was widest for the visual stimulation factor (0.830), and a score of 9 (full score 24) had the best sensitivity (82%) and specificity (74%) for discriminating PPPD patients from controls. Conclusions: We developed a questionnaire that exhibited high reliability and validity in evaluating PPPD severity. The visual stimulation factor may be the most characteristic among the three exacerbating factors.
Acute total hip arthroplasty in acetabular fractures using modern porous metal cup

Purpose: The aim of this study was to report the clinical and radiological outcome of using the modern porous metal cup in patients undergoing acute total hip arthroplasty (THA) for selected subset of acetabular fractures. Patient and methods: Eighteen patients with acetabular fracture underwent acute THA with modern porous metal cup from a single manufacturer. Fifteen males and three females with a mean age of 46.4 years (range 21–57 years) were ambispectively followed up for a minimum period of 48 months. All patients were evaluated clinically with Harris Hip Scores (HHS) and radiographically with serial X-rays. Results: No patient was lost to follow-up. The HHS was excellent in nine patients, good in six patients, fair in two patients, and poor in one patient. All the fractures were united and the cups were well integrated. There was no lucent line seen in any acetabular zones on the X-rays. One patient had infection, which resolved with debridement. There was one dislocation following fall, which was reduced by closed means and remained stable. One of the two patients with heterotopic ossification had restricted movement of hip but not restricting the activities of daily living. No failures of acetabular component were seen in the study. Conclusion: The current study showed that the modern porous metal cup provides sufficient primary stability and appear suitable for primary THA in acute acetabular fractures at mid-term follow-up: (i) In selected fractures, acute THA can be extended to young adult patients as well. (ii) Modern porous metal cup may provide sufficient stability with or without additional fixation required.
Plant–Microbe Symbiosis: What Has Proteomics Taught Us?

Beneficial microbes have a positive impact on the productivity and fitness of the host plant. A better understanding of the biological impacts and underlying mechanisms by which the host derives these benefits will help to address concerns around global food production and security. The recent development of omics‐based technologies has broadened our understanding of the molecular aspects of beneficial plant–microbe symbiosis. Specifically, proteomics has led to the identification and characterization of several novel symbiosis‐specific and symbiosis‐related proteins and post‐translational modifications that play a critical role in mediating symbiotic plant–microbe interactions and have helped assess the underlying molecular aspects of the symbiotic relationship. Integration of proteomic data with other “omics” data can provide valuable information to assess hypotheses regarding the underlying mechanism of symbiosis and help define the factors affecting the outcome of symbiosis. Herein, an update is provided on the current and potential applications of symbiosis‐based “omic” approaches to dissect different aspects of symbiotic plant interactions. The application of proteomics, metaproteomics, and secretomics as enabling approaches for the functional analysis of plant‐associated microbial communities is also discussed.
Temperature dependence of gate current in ultra thin SiO/sub 2/ in direct-tunneling regime

In this paper, we examine the temperature dependence of gate current in the direct tunneling regime in ultra thin oxide MOS capacitors under positive and negative gate bias. It was found that for temperature above /spl sim/348 K and low fields, the gate current is exponentially dependent on 1/T. In this temperature range, it was found that gate current is dominated by a thermionic-type of emission current. However, below /spl sim/348 K, the gate current is weakly dependent on temperature and is dominated by field activated direct tunneling. This finding holds for PMOS and NMOS devices operating in accumulation and inversion. The activation energies for the thermionic-type emission for different gate voltage conditions were determined from the Arrhenius plots to be between 0.64 eV and 0.84 eV for PMOS and between 0.73 eV and 0.82 eV for NMOS. It was also found that the activation energy decreases with increasing gate voltage. In addition, it was found that the activation energy is lower for injection from p-type electrodes than that for injection from n-type electrodes.
Effect of Mongolian warm acupuncture on the gene expression profile of rats with insomnia

Background: The mechanism of Mongolian warm acupuncture (MWA) for the treatment of insomnia has not been previously reported. Objective: To investigate the effect of MWA on gene expression profile in the p-chlorophenylalanine (PCPA)-induced rat model of insomnia. Methods A rat model of insomnia was established and the animals were divided into five groups: control, PCPA (untreated), PCPA+estazolam, PCPA+MA (manual acupuncture), and PCPA+MWA. The rats were euthanased at 7 days after treatment, and hypothalamic tissue was harvested to extract total RNA for the analysis of gene expression profile. Micro-array and Partek Genomics Suite analysis system were used to analyse differential expression of genes between groups. Furthermore, ingenuity pathways analysis was used to analyse the main regulators. Results: After treatment, in rats with improved sleep, micro-array data from the follow-up phase compared with baseline showed that MWA down-regulated 11 genes compared with the control group and 16 genes compared with the PCPA group. Six genes were selected following the micro-array detection to perform quantitative polymerase chain reaction (qPCR) verification, and the results showed that the coincidence rate was up to 90%, which verified the reliability of the microarray results. Compared with the PCPA group, transcription levels of Egr 1, Btg2 and BDNF in the PCPA+MWA group were up-regulated (P<0.05). Conclusion: In combination, the findings of this study suggests that MWA is efficacious at improving sleep in an experimental rat model of insomnia.
Qigong and Tai Chi as Therapeutic Exercise: Survey of Systematic Reviews and Meta-Analyses Addressing Physical Health Conditions.

Context Many researchers are interested in the Eastern therapeutic exercise of qigong and tai chi, performed as qigong. A review of systematic studies through April 2010 found evidence supporting tai chi as effective for preventing falls, improving psychological health, and promoting healthy aging. Objective The review intended to provide an updated survey of recent systematic reviews to establish the current-2016-level of scientific evidence assessing the therapeutic benefits of qigong exercise for clinical applications related to physical health. Methods The data sources included PubMed, SCOPUS, and CINAHL, using the major terms qigong OR tai chi AND review. Studies were included in the review if they (1) were systematic reviews and meta-analyses; (2) had been published as full text in the English language; (3) were published between January 2010 and December 2016; (4) had tai chi or qigong as the primary intervention of interest; (5) addressed a defined, physical-health complaint; and (6) included ≥3 randomized clinical trials. Reviews addressing nonclinical topics, mental health, and cognition were excluded. Results The extensive search identified 41 relevant systematic reviews and meta-analyses. Five areas of clinical application were supported. The review showed independent research evidence that was sufficient to support tai chi performed as qigong as a primary intervention for balance training and fall prevention. When compared with more traditional interventions, tai chi was found to have equal, and in some instances, superior effects, as well as cost-effectiveness. In addition, qigong, and tai chi performed as qigong, were found to have a complementary or alternative role in management of cancer, chronic obstructive pulmonary disease, Parkinson's disease, and cardiac and cardiovascular disorders. Conclusions A growing body of evidence supports qigong and tai chi performed as qigong as valid complementary or alternative therapeutic exercises. Many aspects of the clinical study and application in this area remain to be explored.