Miracle-dz/UniFAR-FTUs huggingface dataset:
Quantity and Quality of Sleep and Incidence of Type 2 Diabetes

OBJECTIVE To assess the relationship between habitual sleep disturbances and the incidence of type 2 diabetes and to obtain an estimate of the risk. RESEARCH DESIGN AND METHODS We conducted a systematic search of publications using MEDLINE (1955–April 2009), EMBASE, and the Cochrane Library and manual searches without language restrictions. We included studies if they were prospective with follow-up >3 years and had an assessment of sleep disturbances at baseline and incidence of type 2 diabetes. We recorded several characteristics for each study. We extracted quantity and quality of sleep, how they were assessed, and incident cases defined with different validated methods. We extracted relative risks (RRs) and 95% CI and pooled them using random-effects models. We performed sensitivity analysis and assessed heterogeneity and publication bias. RESULTS We included 10 studies (13 independent cohort samples; 107,756 male and female participants, follow-up range 4.2–32 years, and 3,586 incident cases of type 2 diabetes). In pooled analyses, quantity and quality of sleep predicted the risk of development of type 2 diabetes. For short duration of sleep (≤5–6 h/night), the RR was 1.28 (95% CI 1.03–1.60, P = 0.024, heterogeneity P = 0.015); for long duration of sleep (>8–9 h/night), the RR was 1.48 (1.13–1.96, P = 0.005); for difficulty in initiating sleep, the RR was 1.57 (1.25–1.97, P < 0.0001); and for difficulty in maintaining sleep, the RR was 1.84 (1.39–2.43, P < 0.0001). CONCLUSIONS Quantity and quality of sleep consistently and significantly predict the risk of the development of type 2 diabetes. The mechanisms underlying this relation may differ between short and long sleepers.
Dose-related effects of cerulein short infusions on proximal small bowel motility in sheep

INTRODUCTION Duodenal motility is a very important intestinal phenomenon, crucial for normal digestion and absorption, and its motor functions are controlled by many neurohormonal mechanisms. Cholecystokinin (CCK) is one of the principal gastrointestinal hormones involved in this control. The role of the hormone is not limited to motility and it also participates in the control of other physiological functions. In humans and monogastric animals, CCK affects the motor activity of the whole gastrointestinal tract in vivo and in vitro. The recognised effect of CCK on small-intestinal motility is clear. The hormone inhibits the arrival of the migrating motor complex (MMC) in the upper small bowel. Furthermore, it evokes the specific spike burst pattern and may increase spiking activity as well as hasten intestinal transit time. Its amphibian analogue, cerulein, is also active in mammals. In sheep, CCK peptides are also active in modulation of gastrointestinal motility, inhibit the arrival of the MMC in the upper small intestine and affect contractile activity, but their influence on intestinal motility has not been fully elucidated although several studies have been undertaken. The dual effect of CCK on small-intestinal motility can also be expected to occur in sheep. The duodenal spiking activity response to CCK and whether there is a difference in this response between the duodenal bulb and the duodenum in conscious sheep have still to be elucidated.
Comparative Analyses between Retained Introns and Constitutively Spliced Introns in Arabidopsis thaliana Using Random Forest and Support Vector Machine

One of the important modes of pre-mRNA post-transcriptional modification is alternative splicing. Alternative splicing allows creation of many distinct mature mRNA transcripts from a single gene by utilizing different splice sites. In plants like Arabidopsis thaliana, the most common type of alternative splicing is intron retention. Many studies in the past focus on positional distribution of retained introns (RIs) among different genic regions and their expression regulations, while little systematic classification of RIs from constitutively spliced introns (CSIs) has been conducted using machine learning approaches. We used random forest and support vector machine (SVM) with radial basis kernel function (RBF) to differentiate these two types of introns in Arabidopsis. By comparing coordinates of introns of all annotated mRNAs from TAIR10, we obtained our high-quality experimental data. To distinguish RIs from CSIs, We investigated the unique characteristics of RIs in comparison with CSIs and finally extracted 37 quantitative features: local and global nucleotide sequence features of introns, frequent motifs, the signal strength of splice sites, and the similarity between sequences of introns and their flanking regions. We demonstrated that our proposed feature extraction approach was more accurate in effectively classifying RIs from CSIs in comparison with other four approaches. The optimal penalty parameter C and the RBF kernel parameter in SVM were set based on particle swarm optimization algorithm (PSOSVM). Our classification performance showed F-Measure of 80.8% (random forest) and 77.4% (PSOSVM). Not only the basic sequence features and positional distribution characteristics of RIs were obtained, but also putative regulatory motifs in intron splicing were predicted based on our feature extraction approach. Clearly, our study will facilitate a better understanding of underlying mechanisms involved in intron retention.
Simple Question Answering by Attentive Convolutional Neural Network

This work focuses on answering single-relation factoid questions over Freebase. Each question can acquire the answer from a single fact of form (subject, predicate, object) in Freebase. This task, simple question answering (SimpleQA), can be addressed via a two-step pipeline: entity linking and fact selection. In fact selection, we match the subject entity in a fact candidate with the entity mention in the question by a character-level convolutional neural network (char-CNN), and match the predicate in that fact with the question by a word-level CNN (word-CNN). This work makes two main contributions. (i) A simple and effective entity linker over Freebase is proposed. Our entity linker outperforms the state-of-the-art entity linker over SimpleQA task. (ii) A novel attentive maxpooling is stacked over word-CNN, so that the predicate representation can be matched with the predicate-focused question representation more effectively. Experiments show that our system sets new state-of-the-art in this task.
IGF-1, the Cross Road of the Nutritional, Inflammatory and Hormonal Pathways to Frailty

The decline in functional capacity is a heterogeneous phenomenon in the elderly. An accelerated ageing determines a frail status. It results in an increased vulnerability to stressors for decreased physiological reserves. The early identification of a frail status is essential for preventing loss of functional capacity, and its clinical consequences. Frailty and mobility limitation result from an interplay of different pathways including multiple anabolic deficiency, inflammation, oxidative stress, and a poor nutritional status. However, the age-related decline in insulin-like growth factor 1 (IGF-1) bioactivity deserves special attention as it could represent the ideal crossroad of endocrine, inflammatory, and nutritional pathways to frailty. Several minerals, namely magnesium, selenium, and zinc, appear to be important determinants of IGF-1 bioactivity. This review aims to provide an overview of the potential usefulness of nutrients modulating IGF-1 as potential therapeutic targets in the prevention of mobility limitation occurring in frail older subjects.
Providing Rapid Out of Hospital Acute Cardiovascular Treatment 4 (PROACT‐4)

Background Whether prehospital point‐of‐care (POC) troponin further accelerates the time to diagnosis in patients with chest pain (CP) is unknown. We conducted a randomized trial of POC‐Troponin testing in the ambulance. Methods and Results Patients with chest pain presenting by ambulance were randomized to usual care (UC) or POC‐Troponin; ST‐elevation myocardial infarction patients or those with noncardiovascular symptoms were excluded. Pre‐hospital high‐sensitivity troponin was analyzed on a POC device and available to the paramedic and emergency department (ED) staff. The final diagnosis was centrally adjudicated. The primary endpoint was time from first medical contact to discharge from ED or admission to hospital. We randomized 601 patients in 19 months; 296 to UC and 305 to POC‐Troponin. After ambulance arrival, the first troponin was available in 38 minutes in POC‐Troponin and 139 minutes in UC. In POC‐Troponin, the troponin was >0.01 ng/mL in 17.4% and >0.03 ng/mL in 9.8%. Patients spent a median of 9.0 hours from first medical contact to final disposition, and 165 (27.4%) were admitted to the hospital. The primary endpoint was shorter in patients randomized to POC‐Troponin (median 8.8 hours [6.2–10.8] compared to UC (median 9.1 hours [6.7–11.2]; P=0.05). There was no difference in the secondary endpoint of repeat ED visits, hospitalizations, or death in the next 30 days. Conclusions In this broad population of patients with CP, ambulance POC‐Troponin accelerated the time to final disposition. Enhanced and more cost‐effective early ED discharge of the majority of patients with CP calling 911 is an unrealized opportunity. Clinical Trial Registration URL: https://www.ClinicalTrials. gov/. Unique identifier: NCT01634425.
Surgical Ineligibility and Mortality Among Patients With Unprotected Left Main or Multivessel Coronary Artery Disease Undergoing Percutaneous Coronary Intervention

Background— Decisions to proceed with surgical versus percutaneous revascularization for multivessel coronary artery disease are often based on subtle clinical information that may not be captured in contemporary registries. The present study sought to evaluate the association between surgical ineligibility documented in the medical record and long-term mortality among patients with unprotected left main or multivessel coronary artery disease undergoing percutaneous coronary intervention. Methods and Results— All subjects undergoing nonemergent percutaneous coronary intervention for unprotected left main or multivessel coronary artery disease were identified at 2 academic medical centers from 2009 to 2012. Documentation of surgical ineligibility was assessed through review of electronic medical records. Cox proportional hazard models adjusted for known mortality risk factors were created to assess long-term mortality in patients with and without documentation of surgical ineligibility. Among 1013 subjects with multivessel coronary artery disease, 218 (22%) were deemed ineligible for coronary artery bypass graft surgery. The most common explicitly cited reasons for surgical ineligibility in the medical record were poor surgical targets (24%), advanced age (16%), and renal insufficiency (16%). After adjustment for known risk factors, documentation of surgical ineligibility remained independently associated with an increased risk of in-hospital (odds ratio, 6.26; 95% confidence interval, 2.16–18.15; P<0.001) and long-term mortality (hazard ratio, 2.98; 95% confidence interval, 1.88–4.72, P<0.001) after percutaneous coronary intervention. Conclusions— Documented surgical ineligibility is common and associated with significantly increased long-term mortality among patients undergoing percutaneous coronary intervention with unprotected left main or multivessel coronary disease, even after adjustment for known risk factors for adverse events during percutaneous revascularization.
Primate Seed Dispersal: The Fate of Dispersed Seeds1

The three primate species of Santa Rosa National Park, Costa Rica (Ateles geoffroyi, Alouatta palliata, Cebus capucinus) have diets in which fruits are major components. All three primate species defecated seeds of many fruiting species; the majority of which (60%) germinated under experimental conditions. The sampling of seed traps placed throughout the forest indicated that, on average, 392 large seeds that passed through the stomachs of monkeys fell weekly per hectare of forest floor. However, the dispersal performed by the primates may not be the final stage of dispersal for many of these seeds. By constructing artificial dung piles containing seeds it was shown that 51.8 percent of the seeds were either removed by secondary dispersers, or killed by seed predators within 5 days of being placed in the forest. The rate of seed removal varied depending on the seed species.
Using Sparse Parameter Estimation for Semantic Parsing

This paper addresses the problem of semantic parsing, by which natural language sentences are translated into a form which conveys their underlying meaning. Semantic parsing involves a parameter estimation process, which is a convex optimization problem. The optimization formulation of previous approaches often requires huge amount of time to converge due to the high dimensional feature space. In this paper we introduce a fast semantic parsing framework which uses l1norm regularized learning to get a sparse model and better convergence speed. Experiments demonstrate overall higher performance of our semantic parsing system using inverse λ, generalization and l1 regularization. Regularized parameter updating shows significantly improvement on the learning speed and reduced model size.
Nonlinear effects in macromolecular assembly and dosage sensitivity.

Haploinsufficiency refers to dominant abnormal phenotypes resulting from the absence of substantial activity from one allele at a normally diploid locus. Haploinsufficiency may also result from an altered stoichiometry in a macromolecular complex. Higher-than-diploid levels of a gene product can also induce abnormalities that may even resemble the haploinsufficient phenotype. Here, I explore possible non-linearities in the assembly of multimeric molecules from the perspective of dose effects. I propose that for any oligomer assembly reaction, there may be a set of conditions (initial subunit concentrations and equilibrium constants) such that changing the input concentration of one component (0.5 x or 1.5x) will lead to a minimum and non-proportional change of the final oligomer concentration. This buffer effect is a general property of multimeric systems in equilibrium and can be, in principle, exploited by selection to diminish dosage sensitivity. Other effects involving cooperativity or sequential assembly may also play a role in palliating the effect of changes in input amounts of monomers.
Increasing Experience with Primary Oral Medical Therapy for Mycobacterium ulcerans Disease in an Australian Cohort

ABSTRACT Buruli ulcer (BU) is a necrotizing infection of subcutaneous tissue that is caused by Mycobacterium ulcerans and is responsible for disfiguring skin lesions. The disease is endemic to specific geographic regions in the state of Victoria in southeastern Australia. Growing evidence of the effectiveness of antibiotic therapy for M. ulcerans disease has evolved our practice to the use of primarily oral medical therapy. An observational cohort study was performed on all confirmed M. ulcerans cases treated with primary rifampin-based medical therapy at Barwon Health between October 2010 and December 2014 and receiving 12 months of follow-up. One hundred thirty-two patients were managed with primary medical therapy. The median age of patients was 49 years, and nearly 10% had diabetes mellitus. Lesions were ulcerative in 83.3% of patients and at WHO stage 1 in 78.8% of patients. The median duration of therapy was 56 days, with 22 patients (16.7%) completing fewer than 56 days of antimicrobial treatment. Antibiotic-associated complications requiring cessation of one or more antibiotics occurred in 21 (15.9%) patients. Limited surgical debridement was performed on 30 of these medically managed patients (22.7%). Cure was achieved, with healing within 12 months, in 131 of 132 patients (99.2%), and cosmetic outcomes were excellent. Primary rifampin-based oral medical therapy for M. ulcerans disease, combined with either clarithromycin or a fluoroquinolone, has an excellent rate of cure and an acceptable toxicity profile in Australian patients. We advocate for further research to determine the optimal and safest minimum duration of medical therapy for BU.
Latent Membrane Protein 2A-Mediated Effects on the Phosphatidylinositol 3-Kinase/Akt Pathway

ABSTRACT Epstein-Barr virus (EBV) latent membrane protein 2A (LMP2A) is expressed on the membranes of B lymphocytes and blocks B-cell receptor (BCR) signaling in EBV-transformed B lymphocytes in vitro. The phosphotyrosine motifs at positions 74 or 85 and 112 within the LMP2A amino-terminal domain are essential for the LMP2A-mediated block of B-cell signal transduction. In vivo studies indicate that LMP2A allows B-cell survival in the absence of normal BCR signals. A possible role for Akt in the LMP2A-mediated B-cell survival was investigated. The protein kinase Akt is a crucial regulator of cell survival and is activated within B lymphocytes upon BCR cross-linking. LMP2A expression resulted in the constitutive phosphorylation of Akt, and this LMP2A effect is dependent on phosphatidylinositol 3-kinase activity. In addition, recruitment of Syk and Lyn protein tyrosine kinases (PTKs) to tyrosines 74 or 85 and 112, respectively, are critical for LMP2A-mediated Akt phosphorylation. However, the ability of LMP2A to mediate a survival phenotype downstream of Akt could not be detected in EBV-negative Akata cells. This would indicate that LMP2A is not responsible for EBV-dependent Burkitt's lymphoma cell survival.
Convection-Radiation Heat Transfer in a Nonlinear Fluid with Temperature-Dependent Viscosity

We will study the fully developed flow of a generalized second-grade fluid down an inclined plane. The viscosity is not only a function of the shear rate (shear-thinning or shear-thickening) but also depends on the temperature in an exponential way. The effects of radiation boundary condition at the free surface are considered. The boundary value problem is solved numerically, and the velocity and temperature profiles are obtained for various dimensionless numbers.
SimpleConcepts: Support for constraints on generic types in C++

Generic programming plays an essential role in C++ software through the use of templates. However, both the creation and use of template libraries is hindered by the fact that the language does not allow programmers to specify constraints on generic types. To date, no proposal to update the language to provide concepts has survived the committee process. Until that time comes, as a form of early support, this paper introduces SimpleConcepts, an extension to C++11 that provides support for concepts, sets of constraints on generic types. SimpleConcepts features are parsed according to an island grammar and source-to-source translation is used to lower concepts to pure C++11 code.
The effect of quetiapine on psychosis and motor function in parkinsonian patients with and without dementia

Recently, several small studies have indicated that quetiapine may be useful in the treatment of drug‐induced psychosis in patients with PD. However, there have been questions related to atypical antipsychotic therapy and patient selection and how that may affect response and tolerability, especially worsening of the motor symptoms of PD. In particular, the presence or absence of dementia seems to be important. The aim of this study was to evaluate the effect of quetiapine on psychosis and motor symptoms in PD patients with and without dementia. A retrospective record review of patient responses to quetiapine was conducted. Response of psychosis was assessed through patient and caregiver interviews. Motor symptom change in relation to this therapy was assessed by patient and caregiver interviews and completion of the motor portion of the Unified Parkinson's Disease Rating Scale (UPDRSm). Analysis was performed by comparing psychosis and motor feature measures from before and after therapy for the group as a whole and for demented and nondemented subgroups, using nonparametric tests and Fisher's exact test. Forty‐three consecutively treated PD patients were evaluated. The mean dose of quetiapine was 54 mg per day and the duration of therapy was 10 months. Eighty‐one percent of patients demonstrated partial or complete amelioration of psychosis. Five patients (13%) experienced a worsening of PD motor symptoms, which was corroborated by changes seen in UPDRSm. When the group was examined as a whole, no significant change in UPDRSm score was noted. When demented (n = 20) and nondemented (n = 19) patients were compared, improvement in psychosis occurred in similar numbers of patients, but a significant difference in the numbers of patients who experienced a worsening of motor symptoms was seen (P < 0.02, Fisher's exact test). All five patients who complained of motor worsening were in the demented group. UPDRSm score after therapy tended to be worse in the demented group (P = 0.55, Mann‐Whitney U test). There was no significant change in the levodopa dose. Approximately 80% of patients chose to continue therapy. We conclude that quetiapine is effective in improving psychosis in approximately 80% of PD patients both with and without dementia. Patients with dementia seem to have a higher propensity for worsening of motor symptoms.
Quantification of fetal microchimeric cells in clinically affected and unaffected skin of patients with systemic sclerosis.

OBJECTIVE Fetal microchimerism has been hypothesized as a potential pathogenic mechanism for systemic sclerosis (SSc). This hypothesis was based on the clinical similarities between SSc and graft-vs-host disease and the identification of microchimeric cells in affected SSc tissues. The aim of this study was to compare the quantity of microchimeric cells in clinically affected and non-affected skin of female patients with SSc. METHODS Fluorescence in situ hybridization (FISH) and real-time PCR were employed in paired skin biopsies obtained from clinically affected and unaffected areas from five female SSc patients with diffuse cutaneous SSc (dcSSC) and 10 healthy women. All women in the study had delivered a male fetus. RESULTS FISH analysis revealed the presence of male fetal cells in 1/5 SSc patients (20.0%) compared with 0/10 healthy women (P = 0.0037), whereas quantification by real-time PCR revealed that all SSc samples were positive for male DNA compared with none of the controls. In the five patients with dcSSc, there were similar numbers of microchimeric cells in both affected and unaffected skin (P = 0.4) CONCLUSION The presence of higher numbers of microchimeric cells in clinically unaffected SSc skin, before any clinically detectable evidence of sclerotic changes, suggests that an influx of microchimeric cells may precede the development of tissue fibrosis. This provides additional support to the hypothesis that fetal microchimerism may play a role in the pathogenesis of SSc.