Miracle-dz/UniFAR-FTUs huggingface dataset:
The optimisation of noninvasive ventilation in amyotrophic lateral sclerosis: a systematic review

Background Noninvasive ventilation (NIV) prolongs survival and quality of life in amyotrophic lateral sclerosis (ALS); however, its benefits depend upon the optimisation of both ventilation and adherence. We aimed to identify factors associated with effective initiation and ongoing use of NIV in ALS to develop evidence-based guidance and identify areas for further research. Methods We searched 11 electronic databases (January 1998 to May 2018) for all types of quantitative and qualitative studies. Supplementary grey literature searches were conducted. Records were screened against eligibility criteria, data were extracted from included studies and risk of bias was assessed. We present findings using a narrative synthesis. Results We screened 2430 unique records and included 52 quantitative and six qualitative papers. Factors reported to be associated with NIV optimisation included coordinated multidisciplinary care, place of initiation, selection of interfaces, ventilator modes and settings appropriate for the individual patient, and adequate secretion management. The literature indicated that patients with significant bulbar dysfunction can still derive considerable benefit from NIV if their needs are met. Research emphasises that obstructive airway events, mask leak and uncontrolled secretions should be addressed by adjustments to the interface and machine settings, and the concomitant use of cough augmentation. Conclusion This review highlights that NIV optimisation requires an individualised approach to respiratory management tailored to the differing needs of each patient. Ultimately, this should lead to improved survival and quality of life. This review expands on recommendations in current international guidelines for NIV use in ALS and identifies areas for future research. This systematic review identifies factors associated with the optimal initiation and ongoing monitoring of NIV in patients with ALS. It is recommended to optimise the use of NIV in ALS to improve patient outcomes. http://bit.ly/2L2usJS
Effects of intravenous phosphodiesterase inhibitors and corticosteroids on severe meconium aspiration syndrome.

BACKGROUND Meconium aspiration syndrome (MAS) is a major cause of severe respiratory failure in near- and full-term neonates. Alleviating inflammation is key to successfully treating severe MAS. Phosphodiesterase (PDE) inhibitors are known to play a role in airway smooth muscle relaxation and alveolar inflammation inhibition. This study aimed to investigate the effects of various intravenous (IV) PDE inhibitors and corticosteroids on MAS. METHODS MAS was induced in newborn piglets by instilling human meconium in them. The piglets were randomly divided into five groups (n = 5 in each group): (1) control (sham treatment); (2) dexamethasone (Dex) (IV 0.6 mg/kg of dexamethasone); (3) aminophylline (Ami) (IV 6 mg/kg of aminophylline, followed by continuous infusion of 0.5 mg/kg/h of aminophylline; (4) milrinone (Mil) (IV 50 μg/kg of milrinone, followed by continuous infusion of 0.75 μg/kg/h of milrinone); and (5) rolipram (Rol) (IV 0.8 mg/kg of rolipram). The duration of the experimental period was 4 hours. RESULTS Compared to the control group, all the four treatment groups revealed better oxygenation 3 hours and more after the start of treatment. The Rol group had a significantly elevated heart beat (p < 0.05) and relatively lower blood pressure compared to the other groups during the first 2 hours of the experiment. The Dex group had significantly lower interleukin (IL)-1β levels in the lung tissue compared to the other groups (p < 0.05) and significantly lower IL-6 levels compared to the Ami and Mil groups (p < 0.05). Lung histology showed slightly less inflammation and atelectasis in the Dex group compared to the other groups, but lung injury scores showed no significant between-group differences. CONCLUSION Using IV corticosteroids or any type of PDE inhibitors has some beneficial effects in improving oxygenation in MAS. PDE inhibitors are not superior to IV corticosteroids; in fact, adverse cardiovascular effects occur with the phosphodiesterase type 4 (PDE4) inhibitor. Further investigations are required before using IV corticosteroids and PDE inhibitors in future clinical application.
Duration of Perseverative Thinking as Related to Perceived Stress and Blood Pressure: An Ambulatory Monitoring Study.

OBJECTIVE Psychological distress may be intensified and prolonged by perseverative thinking (e.g., rumination, worry). The tendency to engage frequently in perseverative thinking has been linked to increased blood pressure (BP). Research is needed to investigate the physiological consequences of time spent perseverating by testing the momentary association between the duration of perseverative thinking and blood pressure. The present study examines the extent to which the duration of perseverative thinking is associated with momentary perceived stress and ambulatory BP elevations during daily life. METHODS Participants (N = 373) drawn from a larger project on BP and cardiovascular health completed 24-hour ambulatory BP monitoring accompanied by ecological momentary assessments of their perseverative thoughts and feelings. Multilevel models tested associations among perseveration duration, momentary perceived stress, and systolic and diastolic BP, adjusting for person-level and momentary covariates. RESULTS Higher within-subject perseveration duration was associated with higher stress (B = 0.29; 95% confidence interval [CI] = 0.24, 0.33; p < .001). Although higher perseveration duration was not associated with substantially higher systolic (B = 0.16 mmHg; 95% CI = 0.00, 0.33; p = .056) or diastolic (B = 0.07 mmHg, 95% CI = -0.05, 0.19; p = .25) BP, the associations between higher perseveration duration and higher systolic (p = .032) and diastolic (p = .036) BP were significantly mediated by a higher intensity of momentary perceived stress. CONCLUSIONS Findings support the clinically important notion that physiological consequences of perceived stress can be maintained and even heightened by maladaptively prolonged mental activity.
Effects of The Poly(ADP-ribose) Polymerase Inhibitor Olaparib in Cerulein-Induced Pancreatitis.

OBJECTIVE Activation of the constitutive nuclear and mitochondrial enzyme poly(ADP-ribose) polymerase (PARP) has been implicated in the pathogenesis of cell dysfunction, inflammation and organ failure in various forms of critical illness. The objective of our study was to evaluate the efficacy and safety of the clinically approved PARP inhibitor olaparib in an experimental model of pancreatitis in vivo and in a pancreatic cell line subjected to oxidative stress in vitro. The preclinical studies were complemented with analysis of clinical samples to detect PARP activation in pancreatitis. METHODS Mice were subjected to cerulein-induced pancreatitis; circulating mediators and circulating organ injury markers; pancreatic myeloperoxidase and malondialdehyde levels were measured and histology of the pancreas was assessed. In human pancreatic duct epithelial cells (HPDE) subjected to oxidative stress, PARP activation was measured by PAR Western blotting and cell viability and DNA integrity were quantified. In clinical samples, PARP activation was assessed by PAR (the enzymatic product of PARP) immunohistochemistry. RESULTS In male mice subjected to pancreatitis, olaparib (3 mg/kg i.p.) improved pancreatic function: it reduced pancreatic myeloperoxidase and malondialdehyde levels, attenuated the plasma amylase levels, and improved the histological picture of the pancreas. It also attenuated the plasma levels of pro-inflammatory mediators (TNF-α, IL-1β, IL-2, IL-4, IL-6, IL-12, IP-10, KC) but not MCP-1, RANTES or the anti-inflammatory cytokine IL-10. Finally, it prevented the slight, but significant increase in plasma blood urea nitrogen level, suggesting improved renal function. The protective effect of olaparib was also confirmed in female mice. In HPDE cells subjected to oxidative stress olaparib (1 μM) inhibited PARP activity, protected against the loss of cell viability and prevented the loss of cellular NAD levels. Olaparib, at 1-30 μM did not have any adverse effects on DNA integrity. In human pancreatic samples from patients who died of pancreatitis, increased accumulation of PAR was demonstrated. CONCLUSION Olaparib improves organ function and tempers the hyperinflammatory response in pancreatitis. It also protects against pancreatic cell injury in vitro without adversely affecting DNA integrity. Repurposing and eventual clinical introduction of this clinically approved PARP inhibitor may be warranted for the experimental therapy of pancreatitis.
Examining measurement invariance and differences across groups in the support needs of children with and without intellectual disability.

BACKGROUND The purposes of this study were to empirically determine whether the support needs construct is generalizable across children with and without intellectual disability and to conduct cross-group comparisons to explore how extraordinary and non-extraordinary support needs differ in children. METHOD One thousand thirty-six children (814 with intellectual disability 222 without intellectual disability) were assessed using the SIS-C. RESULTS The SIS-C achieved scalar invariance between children with and without intellectual disability. Cross-group comparisons revealed differences in variances, in correlations between factors and significant latent mean differences for all factors. CONCLUSION Results show that the support needs construct is generalizable to children with and without intellectual disability and that there are no qualitative differences in how they show their support needs, so typically developing children can be used as a reference group to explore differences between extraordinary and non-extraordinary support needs. Conceptual and practical implications are discussed, and future lines of research are provided.
Vascular function and stiffness: population epidemiology and concordance in Australian children aged 11–12 years and their parents

Objectives To describe the epidemiology and parent–child concordance of vascular function in a population-based sample of Australian parent–child dyads at child age 11–12 years. Design Cross-sectional study (Child Health CheckPoint), nested within a prospective cohort study, the Longitudinal Study of Australian Children (LSAC). Setting Assessment centres in seven major Australian cities and eight regional towns or home visits, February 2015–March 2016. Participants Of all participating CheckPoint families (n=1874), 1840 children (49% girls) and 1802 parents (88% mothers) provided vascular function data. Survey weights and methods were applied to account for LSAC’s complex sample design and clustering within postcodes and strata. Outcome measures The SphygmoCor XCEL assessed vascular function, generating estimates of brachial and central systolic blood pressure and diastolic blood pressure, central pulse pressure, augmentation index and carotid–femoral pulse wave velocity. Pearson’s correlation coefficients and multivariable linear regression models estimated parent–child concordance. Results Hypertension was present in 3.9% of children and 9.0% of parents. Mean child and parent values for augmentation index were 4.5% (SD 11.6) and 21.3% (SD 12.3), respectively, and those for carotid–femoral pulse wave velocity were 4.48 m/s (SD 0.59) and 6.85 m/s (SD 1.14), respectively. Parent–child correlation for brachial systolic blood pressure was 0.20 (95% CI 0.15 to 0.24), brachial diastolic blood pressure 0.21 (95% CI 0.16 to 0.26), central systolic blood pressure 0.21 (95% CI 0.16 to 0.25), central diastolic blood pressure 0.21 (95% CI0.17 to 0.26), central pulse pressure 0.19 (95% CI 0.14 to 0.24), augmentation index 0.28 (95% CI 0.23 to 0.32) and pulse wave velocity 0.22 (95% CI 0.18 to 0.27). Conclusions We report Australian values for traditional and more novel vascular function markers, providing a reference for future population studies. Cross-generational concordance in multiple vascular function markers is already established by age 11–12 years, with mechanisms of heritability remaining to be explored.
Hybrid intelligent systems for pattern recognition and signal processing

Hybrid Intelligent Systems (HIS) combine intelligent techniques in synergistic architectures in order to provide solutions for complex problems. These systems utilize at least two of the three techniques: fuzzy logic, genetic algorithms and neural networks. The goal of their combination is to amplify their strengths and complement their weaknesses. Research in hybrid intelligent systems primarily focuses on the integration and interaction of different techniques rather than merging different methods to create new techniques. However, it is not always obvious or easy to build HIS architectures that achieve the higher intelligence goal. A good architecture for a hybrid system should match each of its tasks to the appropriate intelligent technique and provide an efficient means for their integration. Classification of signal patterns represents a complex problem due to the voluminous nature of signal patterns. A signal pattern is the combination of a large sequence of values of one or more variables collected over a period of time. Noise is an intrinsic component to all signal pattern applications. Current classification methods are inadequate in classifying large sets of noisy signal patterns. We selected this problem as the target for our new HIS architecture. In this research we developed a new HIS architecture for classifying large sets of signal patterns. Our Hybrid Intelligent Signal Pattern Classifier (HISPC) has demonstrated superior performance with low classification cost and great flexibility on synthetic and real life large data sets. An equally important objective of this research is the study of the software engineering aspect for developing this architecture. A new software engineering process and a set of design and implementation principles were developed in this work. These tools are applicable to the development of any experimental software system.
The medical necessity of advanced molecular testing in the diagnosis and treatment of brain tumor patients.

Accurate pathologic diagnoses, and molecularly informed treatment decisions for a wide variety of cancers, depend on robust clinical molecular testing that uses genomic, epigenomic, and transcriptomic-based tools. Nowhere is this more essential than in the workup of brain tumors, as emphasized by the incorporation of molecular criteria into the 2016 World Health Organization classification of central nervous system tumors, and the updated official guidelines of the National Comprehensive Cancer Network®. Despite the medical necessity of molecular testing in brain tumors, access to and utilization of molecular diagnostics is still highly variable across institutions, and a lack of reimbursement for such testing remains a significant obstacle. The objectives of this review are (i) to identify barriers to adoption of molecular testing in brain tumors, (ii) to describe the current molecular tools recommended for the clinical evaluation of brain tumors; (iii) to summarize how molecular data are interpreted to guide clinical care, so as to improve understanding and justification for their coverage in the routine workup of adult and pediatric brain tumor cases.
Deep semantic lung segmentation for tracking potential pulmonary perfusion biomarkers in chronic obstructive pulmonary disease (COPD): The multi‐ethnic study of atherosclerosis COPD study

Chronic obstructive pulmonary disease (COPD) is associated with high morbidity and mortality. Identification of imaging biomarkers for phenotyping is necessary for future treatment and therapy monitoring. However, translation of visual analytic pipelines into clinics or their use in large‐scale studies is significantly slowed by time‐consuming postprocessing steps.
Prevention of brain damage after traumatic brain injury by pharmacological enhancement of KCNQ (Kv7, “M-type”) K+ currents in neurons

Nearly three million people in the USA suffer traumatic brain injury (TBI) yearly; however, there are no pre- or post-TBI treatment options available. KCNQ2-5 voltage-gated K+ channels underlie the neuronal “M current”, which plays a dominant role in the regulation of neuronal excitability. Our strategy towards prevention of TBI-induced brain damage is predicated on the suggested hyper-excitability of neurons induced by TBIs, and the decrease in neuronal excitation upon pharmacological augmentation of M/KCNQ K+ currents. Seizures are very common after a TBI, making further seizures and development of epilepsy disease more likely. Our hypothesis is that TBI-induced hyperexcitability and ischemia/hypoxia lead to metabolic stress, cell death and a maladaptive inflammatory response that causes further downstream morbidity. Using the mouse controlled closed-cortical impact blunt TBI model, we found that systemic administration of the prototype M-channel “opener”, retigabine (RTG), 30 min after TBI, reduces the post-TBI cascade of events, including spontaneous seizures, enhanced susceptibility to chemo-convulsants, metabolic stress, inflammatory responses, blood–brain barrier breakdown, and cell death. This work suggests that acutely reducing neuronal excitability and energy demand via M-current enhancement may be a novel model of therapeutic intervention against post-TBI brain damage and dysfunction.
Globus Pharyngeus: Etiology, Taxonomy, and Response to Electroconvulsive Therapy.

Globus pharyngeus, formerly known as globus hystericus—globus, for short—has been defined as “the sensation of a lump or foreign body in the throat. ” In the most recent, fifth edition of the Diagnostic and Statistical Manual of Mental Disorders, globus is considered a conversion disorder or functional neurological symptom disorder. The symptom presents in primary care at a rate of 6.7 cases per 100,000, and patients are often referred to otolaryngologists or gastroenterologists. In this Clinical Challenge, we review possible etiologies of globus, describe the clinical workup, including laboratory testing and imaging, and discuss the apparent association with gastroesophageal reflux and efforts to provide empiric treatment with proton pump inhibitors. Globus also appears in a variety of psychiatric contexts, though no widely accepted psychiatric treatment is available. In addition, even less is known about how to manage severe cases that interfere with patients’ nutrition and with regimens that include oral medications. In one previously documented case, severe globus responded to treatment with electroconvulsive therapy (ECT). In this Clinical Challenge we report a new case of successful treatment with ECT. We present this case and follow-up questions to three experts in the field of psychiatry in order to better understand the taxonomy of globus and consider whether ECT should be considered as a potential first-line treatment for depression complicated by this symptom.
Social runaway: Fisherian elaboration (or reduction) of socially selected traits via indirect genetic effects

Our understanding of the evolutionary stability of socially selected traits is dominated by sexual selection models originating with R. A. Fisher, in which genetic covariance arising through assortative mating can trigger exponential, runaway trait evolution. To examine whether nonreproductive, socially selected traits experience similar dynamics—social runaway—when assortative mating does not automatically generate a covariance, we modeled the evolution of socially selected badge and donation phenotypes incorporating indirect genetic effects (IGEs) arising from the social environment. We establish a social runaway criterion based on the interaction coefficient, ψ, which describes social effects on badge and donation traits. Our models make several predictions. (1) IGEs can drive the original evolution of altruistic interactions that depend on receiver badges. (2) Donation traits are more likely to be susceptible to IGEs than badge traits. (3) Runaway dynamics in nonsexual, social contexts can occur in the absence of a genetic covariance. (4) Traits elaborated by social runaway are more likely to involve reciprocal, but nonsymmetrical, social plasticity. Models incorporating plasticity to the social environment via IGEs illustrate conditions favoring social runaway, describe a mechanism underlying the origins of costly traits, such as altruism, and support a fundamental role for phenotypic plasticity in rapid social evolution.
Fully automatic catheter segmentation in MRI with 3D convolutional neural networks: application to MRI-guided gynecologic brachytherapy

External-beam radiotherapy followed by high dose rate (HDR) brachytherapy is the standard-of-care for treating gynecologic cancers. The enhanced soft-tissue contrast provided by magnetic resonance imaging (MRI) makes it a valuable imaging modality for diagnosing and treating these cancers. However, in contrast to computed tomography (CT) imaging, the appearance of the brachytherapy catheters, through which radiation sources are inserted to reach the cancerous tissue later on, is often variable across images. This paper reports, for the first time, a new deep-learning-based method for fully automatic segmentation of multiple closely spaced brachytherapy catheters in intraoperative MRI. Represented in the data are 50 gynecologic cancer patients treated by MRI-guided HDR brachytherapy. For each patient, a single intraoperative MRI was used. 826 catheters in the images were manually segmented by an expert radiation physicist who is also a trained radiation oncologist. The number of catheters in a patient ranged between 10 and 35. A deep 3D convolutional neural network (CNN) model was developed and trained. In order to make the learning process more robust, the network was trained 5 times, each time using a different combination of shown patients. Finally, each test case was processed by the five networks and the final segmentation was generated by voting on the obtained five candidate segmentations. 4-fold validation was executed and all the patients were segmented. An average distance error of 2.0 ± 3.4 mm was achieved. False positive and false negative catheters were 6.7% and 1.5% respectively. Average Dice score was equal to 0.60 ± 0.17. The algorithm is available for use in the open source software platform 3D Slicer allowing for wide scale testing and research discussion. In conclusion, to the best of our knowledge, fully automatic segmentation of multiple closely spaced catheters from intraoperative MR images was achieved for the first time in gynecological brachytherapy.
Green Tea Consumption and Esophageal Cancer Risk: A Meta-analysis

Abstract Background: The protective role of green tea against cancer is still unknown. Objectives: To investigate the association between green tea consumption and esophageal cancer risk through meta-analysis. Methods: We searched MEDLINE, EMBASE, Web of Science and Cochrane Library for studies on the relationship between green tea and esophageal cancer risk. We assessed heterogeneity (I2) and publication bias (Begg’s and Egger’s tests). Pooled relative risks (RRs) or odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using random effects models. Results: A total of 20 studies were included. The RRs for all studies was 0.65 (95% CI: 0.57–0.73), with I2 = 75.3% and P = 0. In the subgroup analysis, the following variables showed marked heterogeneity: Asian (RR: 0.64; 95% CI: 0.56–0.73) and non-Asian countries (RR: 0.74; 95% CI: 0.45–1.03), female (RR: 0.55; 95% CI: 0.39–0.71) and male + female (RR: 0.64; 95% CI: 0.54–0.75), case–control study (RR: 0.62; 95% CI: 0.52–0.71), impact factor >3 (RR: 0.65; 95% CI: 0.56–0.75), impact factor <3 (RR: 0.64; 95% CI: 0.48–0.80), Newcastle–Ottawa Scale >7 (RR: 0.82; 95% CI: 0.66–0.97) and Newcastle–Ottawa Scale ≤7 (RR: 0.59; 95% CI: 0.49–0.68). Conclusion: Green tea consumption could be a protective factor for esophageal cancer.