Miracle-dz/UniFAR-FTUs huggingface dataset:
DIAGNOSIS AND MANAGEMENT OF GASTROESOPHAGEAL REFLUX DISEASE

Introduction Gastroesophageal reflux disease (GERD) is probably one of the most prevalent diseases in the world that also compromises the quality of life of the affected significantly. Its incidence in Brazil is 12%, corresponding to 20 million individuals. Objective To update the GERD management and the new trends on diagnosis and treatment, reviewing the international and Brazilian experience on it. Method The literature review was based on papers published on Medline/Pubmed, SciELO, Lilacs, Embase and Cochrane crossing the following headings: gastroesophageal reflux disease, diagnosis, clinical treatment, surgery, fundoplication. Results Various factors are involved on GERD physiopathology, the most important being the transient lower esophageal sphincter relaxation. Clinical manifestations are heartburn, regurgitation (typical symptoms), cough, chest pain, asthma, hoarseness and throat clearing (atypical symptoms), which may be followed or not by typical symptoms. GERD patients may present complications such as peptic stenosis, hemorrhage, and Barrett's esophagus, which is the most important predisposing factor to adenocarcinoma. The GERD diagnosis must be based on the anamnesis and the symptoms must be evaluated in terms of duration, intensity, frequency, triggering and relief factors, pattern of evolution and impact on the patient's quality of life. The diagnosis requires confirmation with different exams. The goal of the clinical treatment is to relieve the symptoms and surgical treatment is indicated for patients who require continued drug use, with intolerance to prolonged clinical treatment and with GERD complications. Conclusion GERD is a major digestive health problem and affect 12% of Brazilian people. The anamnesis is fundamental for the diagnosis of GERD, with special analysis of the typical and atypical symptoms (duration, intensity, frequency, triggering and relief factors, evolution and impact on the life quality). High digestive endoscopy and esophageal pHmetry are the most sensitive diagnosctic methods. The clinical treatment is useful in controlling the symptoms; however, the great problem is keeping the patients asymptomatic over time. Surgical treatment is indicated for patients who required continued drug use, intolerant to the drugs and with complicated forms of GERD.
Risk of myocardial infarction (MI) and death following MI in people with chronic obstructive pulmonary disease (COPD): a systematic review and meta-analysis

Objectives Cardiovascular disease is an important comorbidity in patients with chronic obstructive pulmonary disease (COPD). We aimed to systematically review the evidence for: (1) risk of myocardial infarction (MI) in people with COPD; (2) risk of MI associated with acute exacerbation of COPD (AECOPD); (3) risk of death after MI in people with COPD. Design Systematic review and meta-analysis. Methods MEDLINE, EMBASE and SCI were searched up to January 2015. Two reviewers screened abstracts and full text records, extracted data and assessed studies for risk of bias. We used the generic inverse variance method to pool effect estimates, where possible. Evidence was synthesised in a narrative review where meta-analysis was not possible. Results Searches yielded 8362 records, and 24 observational studies were included. Meta-analysis showed increased risk of MI associated with COPD (HR 1.72, 95% CI 1.22 to 2.42) for cohort analyses, but not in case–control studies: OR 1.18 (0.80 to 1.76). Both included studies that investigated the risk of MI associated with AECOPD found an increased risk of MI after AECOPD (incidence rate ratios, IRR 2.27, 1.10 to 4.70, and IRR 13.04, 1.71 to 99.7). Meta-analysis showed weak evidence for increased risk of death for patients with COPD in hospital after MI (OR 1.13, 0.97 to 1.31). However, meta-analysis showed an increased risk of death after MI for patients with COPD during follow-up (HR 1.26, 1.13 to 1.40). Conclusions There is good evidence that COPD is associated with increased risk of MI; however, it is unclear to what extent this association is due to smoking status. There is some evidence that the risk of MI is higher during AECOPD than stable periods. There is poor evidence that COPD is associated with increased in hospital mortality after an MI, and good evidence that longer term mortality is higher for patients with COPD after an MI.
In Vitro Microtumors Provide a Physiologically Predictive Tool for Breast Cancer Therapeutic Screening

Many anti-cancer drugs fail in human trials despite showing efficacy in preclinical models. It is clear that the in vitro assays involving 2D monoculture do not reflect the complex extracellular matrix, chemical, and cellular microenvironment of the tumor tissue, and this may explain the failure of 2D models to predict clinical efficacy. We first optimized an in vitro microtumor model using a tumor-aligned ECM, a tumor-aligned medium, MCF-7 and MDA-MB-231 breast cancer spheroids, human umbilical vein endothelial cells, and human stromal cells to recapitulate the tissue architecture, chemical environment, and cellular organization of a growing and invading tumor. We assayed the microtumor for cell proliferation and invasion in a tumor-aligned extracellular matrix, exhibiting collagen deposition, acidity, glucose deprivation, and hypoxia. We found maximal proliferation and invasion when the multicellular spheroids were cultured in a tumor-aligned medium, having low pH and low glucose, with 10% fetal bovine serum under hypoxic conditions. In a 7-day assay, varying doses of fluorouracil or paclitaxel had differential effects on proliferation for MCF-7 and MDA-MB-231 tumor spheroids in microtumor compared to 2D and 3D monoculture. The microtumors exhibited a tumor morphology and drug response similar to published xenograft data, thus demonstrating a more physiologically predictive in vitro model.
Petri Nets and Bisimulations

Several categorical relationships (adjunctions) between models for concurrency have been established, allowing the translation of concepts and properties from one model to another. The purpose of the present paper is twofold: firstly to present a central example of such a relationship (a coreflection between asynchronous transition systems and Petri nets), and secondly to illustrate its use by transferring to nets a general concept of bisimulation.
Using Phenotypic Heterogeneity to Increase the Power of Genome‐Wide Association Studies: Application to Age at Onset of Ischaemic Stroke Subphenotypes

Genome‐wide association studies (GWAS) have been successful in identifying common variants related to complex disorders. However, some disorders have proved resistant to this strategy with few associations confirmed, despite evidence from twin and family studies of a genetic component. Sophisticated strategies that account for phenotypic heterogeneity may be required to uncover these genetic contributions. Age at onset is an example of a potential source of this heterogeneity in ischaemic stroke. We explore the contribution of age at onset in the Wellcome Trust Case‐Control Consortium 2 ischaemic stroke study. We first examine four established stroke loci in younger onset cases. We extend this to all single‐nucleotide polymorphisms (SNPs) genome‐wide, testing for stronger association signals in younger subsets of cases. Finally, we estimate the pseudoheritability accounted for by common SNPs present on genome‐wide genotyping arrays for cases stratified by age at onset. We find evidence for stronger associations in younger onset cases for the four established stroke loci. Genome‐wide, in cardioembolic and small vessel stroke subphenotypes, a significant number of SNPs show stronger association P‐values when the oldest cases are removed. Finally, we show that the pseudoheritability estimated by common SNPs in cardioembolic stroke increased from 16.5% for older onset cases to 28.5% for younger onset cases. Our results indicate that age at onset is a valuable measure for case ascertainment and in analysis of GWAS in ischaemic stroke: focussing on younger cases who may have a stronger genetic predisposition increases power to detect associations.
The heat shock paradox: does NF‐ κ B determine cell fate?

Cellular injury induces an adaptive response whether the insult is physical (e.g., heat, radiation), chemical (e.g., reactive oxygen species), infectious (e.g., bacteria), or inflammatory (e.g., lipopolysaccharide). Recent data indicate that the interactions of these responses are not predictable and that sequence permutations can have opposite effects on outcome after injury. Our overarching hypothesis is that interactions among stress responses contribute to the fate of cells, tissues, and organisms and that modulation of these interactions can have important affects on both function and survival. For example, whereas it is well known that a prior heat shock stress can protect cells against inflammatory stress both in vitro and in vivo, we and others have shown that induction of a subsequent heat stress in cells ‘primed’ by inflammation can precipitate cell death by apoptosis. We call this seemingly paradoxical ability of heat shock to induce cytoprotection and cytotoxicity the heat shock paradox. The molecular mechanisms by which cells integrate responses to these and other stresses are poorly understood. We present data linking the heat shock paradox to the activity of the acute‐phase transcription factor nuclear factor kappa Β (identifying an ‘NF‐ΚB paradox’) and hypothesize that the mechanism is linked to the downstream effects of induction of NF‐ΚB's endogenous inhibitor, ΙκΒα, a putative heat shock protein. —DeMeester, S. L. , Buchman, T. G. , Cobb, J. P. The heat shock paradox: does NF‐ΚB determine cell fate? FASEB J. 15, 270–274 (2001)
Noninvasive and invasive evaluation of pulmonary arterial pressure in highlanders

The purpose of the present study was to evaluate Doppler echocardiography for the detection of pulmonary hypertension in high-altitude inhabitants. In total, 60 (55 male) patients aged 18–71 yrs were recruited from an ECG screening programme applied to 1,430 inhabitants living at an altitude of 2,500–3,600 m in Kyrgyzstan. Of these, 44 met ECG criteria for right ventricular hypertrophy. All underwent Doppler echocardiography followed by a cardiac catheterisation within 7 days of arrival in Bishkek (Kyrgyzstan; altitude 760 m). Pulmonary flow acceleration time and the maximum velocity of tricuspid regurgitation were measured. Sufficient quality tricuspid regurgitant jets were recovered in only 28% of the patients. Therefore, pulmonary artery pressure was estimated from the pulmonary flow acceleration time, which was recovered in 100% of the patients. It was found that 37 (62%) of the patients had pulmonary hypertension on echocardiography. Pulmonary hypertension was confirmed in 29 patients on catheterisation. Pulmonary hypertension was detected with 70% sensitivity and 88% specificity by echocardiography, as compared to 59% sensitivity and 81 % specificity by ECG. The correlation coefficient between echocardiography and catheterisation studies was r2 = 0.78. It is concluded that a combination of ECG and echocardiography may be useful for screening high-altitude pulmonary hypertension.
The Impact of Antipsychotic Polytherapy Costs in the Public Health Care in Sao Paulo, Brazil

Introduction Guidelines for the treatment of psychoses recommend antipsychotic monotherapy. However, the rate of antipsychotic polytherapy has increased over the last decade, reaching up to 60% in some settings. Studies evaluating the costs and impact of antipsychotic polytherapy in the health system are scarce. Objective To estimate the costs of antipsychotic polytherapy and its impact on public health costs in a sample of subjects with psychotic disorders living in residential facilities in the city of Sao Paulo, Brazil. Method A cross-sectional study that used a bottom-up approach for collecting costs data in a public health provider´s perspective. Subjects with psychosis living in 20 fully-staffed residential facilities in the city of Sao Paulo were assessed for clinical and psychosocial profile, severity of symptoms, quality of life, use of health services and pharmacological treatment. The impact of polytherapy on total direct costs was evaluated. Results 147 subjects were included, 134 used antipsychotics regularly and 38% were in use of antipsychotic polytherapy. There were no significant differences in clinical and psychosocial characteristics between polytherapy and monotherapy groups. Four variables explained 30% of direct costs: the number of antipsychotics, location of the residential facility, time living in the facility and use of olanzapine. The costs of antipsychotics corresponded to 94.4% of the total psychotropic costs and to 49.5% of all health services use when excluding accommodation costs. Olanzapine costs corresponded to 51% of all psychotropic costs. Conclusion Antipsychotic polytherapy is a huge economic burden to public health service, despite the lack of evidence supporting this practice. Great variations on antipsychotic costs explicit the need of establishing protocols for rational antipsychotic prescriptions and consequently optimising resource allocation. Cost-effectiveness studies are necessary to estimate the best value for money among antipsychotics, especially in low and middle income countries.
Learning with Marginalized Corrupted Features

The goal of machine learning is to develop predictors that generalize well to test data. Ideally, this is achieved by training on very large (infinite) training data sets that capture all variations in the data distribution. In the case of finite training data, an effective solution is to extend the training set with artificially created examples--which, however, is also computationally costly. We propose to corrupt training examples with noise from known distributions within the exponential family and present a novel learning algorithm, called marginalized corrupted features (MCF), that trains robust predictors by minimizing the expected value of the loss function under the corrupting distribution-- essentially learning with infinitely many (corrupted) training examples. We show empirically on a variety of data sets that MCF classifiers can be trained efficiently, may generalize substantially better to test data, and are more robust to feature deletion at test time.
Learning The Discriminative Power-Invariance Trade-Off

We investigate the problem of learning optimal descriptors for a given classification task. Many hand-crafted descriptors have been proposed in the literature for measuring visual similarity. Looking past initial differences, what really distinguishes one descriptor from another is the tradeoff that it achieves between discriminative power and invariance. Since this trade-off must vary from task to task, no single descriptor can be optimal in all situations. Our focus, in this paper, is on learning the optimal tradeoff for classification given a particular training set and prior constraints. The problem is posed in the kernel learning framework. We learn the optimal, domain-specific kernel as a combination of base kernels corresponding to base features which achieve different levels of trade-off (such as no invariance, rotation invariance, scale invariance, affine invariance, etc.) This leads to a convex optimisation problem with a unique global optimum which can be solved for efficiently. The method is shown to achieve state-of-the-art performance on the UIUC textures, Oxford flowers and Cal- tech 101 datasets.
The role of sleep problems in the development of depression in those with persistent pain: a prospective cohort study.

STUDY OBJECTIVES One theoretical model suggests a pathway between pain and the development of depression through sleep problems. Here, we prospectively test the hypothesis that incident sleep problems, in those with persistent pain, increase risk of new onset probable depression, and investigate the role of "pain that interferes with daily life" (pain interference) on this pathway. DESIGN Prospective cohort study. SETTING Community based population study within UK. PARTICIPANTS Participants with persistent pain nested within a larger longitudinal community study. MEASUREMENTS Participants were mailed health questionnaires at baseline (time 1) with follow-up at 3 years (time 2) and 6 years from baseline (time 3). Questionnaires at baseline and at follow up contained measures of sleep problems (Jenkins Sleep Questionnaire), depressive symptoms (Hospital Anxiety and Depressive Scale), and pain interference. RESULTS In total, 2,622 participants returned health questionnaires at all time points and indicated the presence of pain at each time point. After adjustment for age, gender, marital status, employment status, alcohol intake, smoking status, and body mass index, having a new period of sleep problems at year 3 more than trebled the risk of a new period of probable depression at year 6 (relative risk 3.47, 95% CI 1.97 to 6.03). Mediation analysis showed that pain interference played a significant but relatively minor role in the pathway. CONCLUSION Clinicians treating patients with persistent pain may wish to consider options that involve addressing the prevention or treatment of sleep problems, in addition to their primary focus of pain management.
SPREADSHEET USE BY ACCOUNTANTS : AUSTRALIA , CANADA & NEW ZEALAND COMPARED

This study uses a self-administered postal questionnaire to compare spreadsheet use by accountants in Australia, Canada and New Zealand in 1996-97. The objectives are to identify differences, if any, between countries in uptake and use of spreadsheets by accountants. Overall the study found a high level of spreadsheet diffusion in all three countries, with Canada being a little ahead of Australia and New Zealand on some evidence. We estimate that in 1996 about 80% of accountants used spreadsheets in Canada and Australia, and slightly less, 75%, in New Zealand. The PC machine is overwhelmingly the preferred hardware platform in all three countries and among accountants; the Apple Macintosh has an insignificant role. Excel is the preferred spreadsheet brand in all three countries, although Lotus is a stronger second in Canada than either of the other two countries. Just over 80% of respondents have a personal computer with sole access at work and just under 80% have access to a computer at home. Budgeting is the clear most frequently done task with spreadsheets in all three countries. Saving time on calculations and being more confident about the accuracy of their work are the most important benefits identified.
Phrenic Nerve Conduction Study in the Early Stage of Guillain–Barre Syndrome as a Predictor of Respiratory Failure

Background: Guillain-Barré syndrome (GBS) has unpredictable clinical course with severe complication of respiratory failure. Objective: To identify clinical profiles and electrophysiological study particularly non-invasive Phrenic nerve conduction study in patients of early GBS to predict respiratory failure. Methods: 64 adult (age≥18yrs) patients of early GBS (onset ≤ 14 days) during the study period from January 2014 to October 2015 were evaluated by clinical profiles of age, gender, antecedent infection, time to peak disability, single breath counts, cranial nerve involvement, autonomic dysfunction and non-invasive Phrenic nerve conduction study. Patients with predisposition factors of polyneuropathy like diabetes mellitus, hypothyroidism, vitamin deficiency, renal failure were excluded. Results: Among 64 patients abnormal phrenic nerve conduction study was seen in 65.62% cases (42/64) and 45.23% (19/42) of them developed respiratory failure. Phrenic nerve sum latency, amplitude, duration and area were abnormal in those who developed respiratory failure and they had sum of phrenic nerve latency >28 msec, sum of CMAP amplitude <300 μV, sum of CMAP duration >50 msec and sum of area < 4 mVmS. None with normal phrenic nerve study developed respiratory failure. It was found that age, gender, preceding infection, autonomic involvement and types of GB syndrome had no influence on development of respiratory failure (p>0.05). Rapid disease progression to peak disability, more severe disease, shorter single breath counts and cranial nerve involvement were seen more often in patients with respiratory failure. Conclusion: Abnormal Phrenic nerve conduction study in the early Guillain-Barré syndrome might be of great value independently in predicting impending respiratory failure.
Dynamic Modulation of Human Motor Activity When Observing Actions

Previous studies have demonstrated that when we observe somebody else executing an action many areas of our own motor systems are active. It has been argued that these motor activations are evidence that we motorically simulate observed actions; this motoric simulation may support various functions such as imitation and action understanding. However, whether motoric simulation is indeed the function of motor activations during action observation is controversial, due to inconsistency in findings. Previous studies have demonstrated dynamic modulations in motor activity when we execute actions. Therefore, if we do motorically simulate observed actions, our motor systems should also be modulated dynamically, and in a corresponding fashion, during action observation. Using magnetoencephalography, we recorded the cortical activity of human participants while they observed actions performed by another person. Here, we show that activity in the human motor system is indeed modulated dynamically during action observation. The finding that activity in the motor system is modulated dynamically when observing actions can explain why studies of action observation using functional magnetic resonance imaging have reported conflicting results, and is consistent with the hypothesis that we motorically simulate observed actions.
Exposure to oral contraceptives increases the risk for development of inflammatory bowel disease: a meta-analysis of case-controlled and cohort studies

Background The oral contraceptive pill (OCP) is a widely used method of contraception. There have been conflicting studies linking the use of OCPs to the development of inflammatory bowel disease (IBD). The intent of this meta-analysis is to better define the association between OCP exposure and the risk for development of IBD. Methods A thorough search of multiple databases, including Scopus, Cochrane, MEDLINE/PubMed, and CINAHL, and abstracts from major gastroenterology meetings was performed (October, 2016). Studies reporting the development of IBD in patients with or without previous exposure to OCP, compared with healthy controls, were included. A meta-analysis was completed using the Mantel–Haenszel model to evaluate the risk of developing IBD in the setting of previous OCP exposure. Results In a complete analysis of 20 studies, there appeared to be over a 30% increased risk for the development of IBD in patients exposed to OCP compared with patients not exposed to OCP [odds ratio (OR): 1.32, 95% confidence interval (CI): 1.17–1.49, P<0.001, I2=14%]. More specifically, there was a 24% higher risk for developing Crohn’s disease (OR: 1.24, 95% CI: 1.09–1.40, P<0.001; I2=38%) and a 30% higher risk for developing ulcerative colitis (OR: 1.30, 95% CI: 1.13–1.49, I2=26%) in patients exposed to OCP compared with those not exposed to the medication. Conclusion The use of OCP is associated with an increased risk for development of Crohn’s disease and ulcerative colitis in the genetically susceptible host. The total duration, dose of OCP exposure, and the risk for development of IBD need to be better characterized.