Miracle-dz/UniFAR-FTUs huggingface dataset:
The Spatio-Temporal Equalization for Evoked or Event-Related Potential Detection in Multichannel EEG Data

Goal: Evoked or Event-Related Potential (EP/ERP) detection is a major area of interest within the domain of EEG (electroencephalography) signal processing. While traditional methods of EEG processing have mostly focused on enhancing signal components, few have explored background noise suppression techniques. Optimizing the suppression of background noise can play a critical role in improving the performance of EP/ERP detection. Methods: In this study, a spatio-temporal equalization (STE) method was proposed based on the Multivariate Autoregressive (MVAR) model, which has been shown to suppress the spatio-temporal correlation of background noise and improve the EEG signal detection performance. Results: For practical applications, two optimization schemes based on the spatio-temporal equalization method were designed to solve two common challenges in EEG signal detection: P300 and steady state visual evoked potentials. Our results demonstrated that the STE method effectively improves recognition performance of evoked or event-related potential detection. Additionally, the STE method offers fewer parameters, lower computational complexity, and easier implementation. Conclusion: These attributes allow the STE approach to be extended as a preprocessing method which can be used in combination with existing techniques.
Morphologic Restoration After Peroral Endoscopic Myotomy in Sigmoid-type Achalasia

Background/Aims Achalasia is a chronic, progressive motility disorder of the esophagus. The sigmoid-type achalasia is an advanced stage of achalasia characterized by severe dilatation and tortuous angulation of the esophageal body. Peroral endoscopic myotomy (POEM) has been reported to provide excellent clinical outcomes for achalasia, including the sigmoid type, but the restoration of esophageal morphology and function remain poorly described. The aim of our study is to investigate esophageal restoration after POEM for sigmoid-type achalasia. Methods From 98 patients with achalasia who underwent POEM in the Yonsei University Health System from 2013 to 2018, we recruited 13 patients with sigmoid-type achalasia (7 male; mean age 53.3 years) and assessed morphological and manometric changes in the esophagus. Results Clinical success (Eckardt score < 3) was achieved in all cases. After POEM, the average angle of esophageal tortuosity became more obtuse (91.5° vs 114.6°, P = 0.046), esophageal body diameter decreased (67.6 vs 49.8 mm, P = 0.002), and esophagogastric junction opening widened (6.4 vs 9.5 mm, P = 0.048). Patients whose esophageal tortuosity did not improve had longer durations of symptoms than patients with improvement (80.2 vs 636 months, P < 0.001). An absence of peristalsis was observed in all patients pre- and post-POEM. Conclusions POEM resulted in excellent clinical outcomes and morphologic improvement in sigmoid-type achalasia. These results suggest that the improvement of esophageal tortuosity through POEM reflects a reduced esophageal burden.
Factors Associated With Intent to Leave in Registered Nurses Working in Acute Care Hospitals: A Cross-Sectional Study in Ontario, Canada

Background: The work environment factors associated with nurses’ intention to leave their jobs are not well understood because most studies have used non-probabilistic sampling methods, thus restricting the generalizability of the results. This study examined the relationship between work environment factors and intent to leave among nurses working in acute care hospitals in Ontario, Canada. Methods: This study included a random sample of 1,427 registered nurses who were part of a larger cross-sectional study and who responded to a mailed survey that included measures of resource availability, interprofessional collaboration, job satisfaction, and demographics. Results: Most of the respondents were female (94.8%), with an average age of 45.6 years, and 14.5 years of nursing experience at their current workplace, which included mostly urban (94.6%) and non-teaching hospitals (61.8%). In the multivariate model, we observed that the work environment variables explained 45.5% of the variance in nurses’ intent to leave scores, F(9, 1362) =125.41, p < . 01, with an R2 of . 455 or 45.5%. Job satisfaction (p < .01), flexible interprofessional collaborative relationships (p = .030), and resource availability (p < .01) were significantly associated with nurses’ intent to leave scores. Conclusion/Application to Practice: Nurses who reported greater job satisfaction, flexible interprofessional relationships, and resource availability were less likely to express an intent to leave their hospital workplaces. Employers and health policy makers may use these findings as part of a broader strategy to improve the work environment of nurses. Occupational health nurses are ideally positioned to demonstrate leadership in promoting retention efforts in the workplace by advocating for the importance of job satisfaction, flexible interprofessional relationships, and resources.
Concurrent affective and linguistic prosody with the same emotional valence elicits a late positive ERP response

Change in linguistic prosody generates a mismatch negativity response (MMN), indicating neural representation of linguistic prosody, while change in affective prosody generates a positive response (P3a), reflecting its motivational salience. However, the neural response to concurrent affective and linguistic prosody is unknown. The present paper investigates the integration of these two prosodic features in the brain by examining the neural response to separate and concurrent processing by electroencephalography (EEG). A spoken pair of Swedish words—[ˈfɑ́ːsɛn] phase and [ˈfɑ̀ːsɛn] damn—that differed in emotional semantics due to linguistic prosody was presented to 16 subjects in an angry and neutral affective prosody using a passive auditory oddball paradigm. Acoustically matched pseudowords—[ˈvɑ́ːsɛm] and [ˈvɑ̀ːsɛm]—were used as controls. Following the constructionist concept of emotions, accentuating the conceptualization of emotions based on language, it was hypothesized that concurrent affective and linguistic prosody with the same valence—angry [ˈfɑ̀ːsɛn] damn—would elicit a unique late EEG signature, reflecting the temporal integration of affective voice with emotional semantics of prosodic origin. In accordance, linguistic prosody elicited an MMN at 300–350 ms, and affective prosody evoked a P3a at 350–400 ms, irrespective of semantics. Beyond these responses, concurrent affective and linguistic prosody evoked a late positive component (LPC) at 820–870 ms in frontal areas, indicating the conceptualization of affective prosody based on linguistic prosody. This study provides evidence that the brain does not only distinguish between these two functions of prosody but also integrates them based on language and experience.
Regional spreading of symptoms at diagnosis as a prognostic marker in amyotrophic lateral sclerosis: a population-based study

Objective The lack of prognostic biomarkers in patients with amyotrophic lateral sclerosis (ALS) induced researchers to develop clinical evaluation tools for stratification and survival prediction. We assessed the correlation between patterns of functional involvement, considered as a cumulative number of body regions involved, and overall survival in a population-based series of patients with ALS (PARALS). Methods We derived the functional involvement of four body regions at diagnosis using ALSFRS-R subscores for bulbar, upper limbs, lower limbs and respiratory/thoracic regions. We analysed the effect of number of body regions involved (NBRI) at diagnosis on overall survival, adjusting for age at onset, sex, site of onset, diagnostic delay, forced vital capacity, body mass index, mutational status, cognition and comparing it with King’s staging system. Results The NBRI was strongly related to survival, with a progressive increase of death/tracheostomy risk among groups (two body regions HR=1.24, 95% CI 1.06 to 1.45, p=0007; three body regions HR=1.65, 95% CI 1.38 to 1.98, p<0.001; four body regions HR=2.68, 95% CI 2.11 to 3.39, p<0.001). Using ALSFRS-R score, the consistency between the number of regions involved and King’s clinical stage at diagnosis was very high (81%). The evaluation of respiratory/thoracic region and cognition allowed to subdivide patients into different prognostic categories. Regional spreading of the disease is associated with survival, independently from the initial region involved. Conclusions The evaluation of NBRI, with the inclusion of initial respiratory/thoracic involvement and cognition, can be useful in many research fields, improving the stratification of patients. Our findings highlight the importance of the spatial spreading of functional impairment in the prediction of ALS outcome.
TRK Fusions Are Enriched in Cancers with Uncommon Histologies and the Absence of Canonical Driver Mutations

Purpose: TRK inhibitors achieve marked tumor-agnostic efficacy in TRK fusion–positive cancers and consequently are now an established standard of care. Little is known, however, about the demographics, outcomes, response to alternative standard therapies, or genomic characteristics of TRK fusion–positive cancers. Experimental Design: Utilizing a center-wide screening program involving more than 26,000 prospectively sequenced patients, genomic and clinical data from all cases with TRK fusions were extracted. An integrated analysis was performed of genomic, therapeutic, and phenomic outcomes. Results: We identified 76 cases with confirmed TRK fusions (0.28% overall prevalence) involving 48 unique rearrangements and 17 cancer types. The presence of a TRK fusion was associated with depletion of concurrent oncogenic drivers (P < 0.001) and lower tumor mutation burden (P < 0.001), with the exception of colorectal cancer where TRK fusions cooccur with microsatellite instability (MSI-H). Longitudinal profiling in a subset of patients indicated that TRK fusions were present in all sampled timepoints in 82% (14/17) of cases. Progression-free survival on first-line therapy, excluding TRK inhibitors, administered for advanced disease was 9.6 months [95% confidence interval (CI), 4.8–13.2]. The best overall response rate achieved with chemotherapy containing–regimens across all lines of therapy was 63% (95% CI, 41–81). Among 12 patients treated with checkpoint inhibitors, a patient with MSI-H colorectal cancer had the only observed response. Conclusions: TRK fusion–positive cancers can respond to alternative standards of care, although efficacy of immunotherapy in the absence of other predictive biomarkers (MSI-H) appears limited. TRK fusions are present in tumors with simple genomes lacking in concurrent drivers that may partially explain the tumor-agnostic efficacy of TRK inhibitors.
Role of PI3K/AKT/mTOR pathway associated oxidative stress and cardiac dysfunction in takotsubo syndrome.

INTRODUCTION Takotsubo syndrome (TTS) is the stress induced cardiomyopathy. But the accurate cause of this syndrome is still unknown. MATERIAL AND METHODS β-adrenergic agonist isoproterenol (ISO) is used to establish the TTS rats model. TTS rats were treated with or without LY294002 or Rapamycin. The rat cardiomyoblast cell line H9C2 was subjected to infected with constitutively active Akt (myr-Akt) or dominant-negative mutant Akt (dn-Akt). Then, treated with ISO. Cell apoptosis was assessed using Bax/ Bcl-2 ratio. In addition, reactive oxygen species (ROS) levels were measured using DHE. Mitochondrial superoxide generation and membrane potential were assayed by MitoSOX and JC-1 fluorescence intensity. RESULTS ISO might induce the erratic acute cardiac dysfunction and overexpression of PI3K/AKT/mTOR. Moreover, it also increased the oxidative stress and apoptosis in TTS rats. The Akt inhibitor significantly reversed the cardiac injury effect which triggered by ISO treatment. In H9C2 cells, the inhibition of Akt provides a protective role against ISO-induced injury by reduce the oxidative stress, apoptosis and mitochondrial dysfunction. CONCLUSION This study provided new insight into the protective effects of myocardial dysfunction in TTS rats via chronic inhibit the PI3K/AKT/mTOR expression which could reduce mitochondrial generate ROS and oxidative stress induced apoptosis. PI3K/AKT/mTOR inhibitor could be a therapeutic target for treating cardiovascular dysfunction induced by stress cardiomyopathy.
Actin protrusions push at apical junctions to maintain E-cadherin adhesion

Significance All solid tissues rely on cadherin family cell–cell adhesion molecules for their cohesion and organization. Cadherin adhesive function depends on the actin cytoskeleton, but actin’s contribution to cell–cell adhesion is not fully understood. We demonstrate that actin polymerization-dependent protrusive activity operates continuously to push lateral membranes of neighboring cells together to keep cadherins in contact. Actin-dependent protrusive activity functions as a safety mechanism to quickly repair cadherin adhesive junctions whenever they fail and to prevent myosin-dependent contractile forces from tearing the junctions further apart. Since loss of cadherin adhesion is associated with a number of diseases including cancer progression, then misregulation of actin protrusive activity should be considered as a possible contributing factor to epithelial pathophysiology. Cadherin-mediated cell–cell adhesion is actin-dependent, but the precise role of actin in maintaining cell–cell adhesion is not fully understood. Actin polymerization-dependent protrusive activity is required to push distally separated cells close enough to initiate contact. Whether protrusive activity is required to maintain adhesion in confluent sheets of epithelial cells is not known. By electron microscopy as well as live cell imaging, we have identified a population of protruding actin microspikes that operate continuously near apical junctions of polarized Madin-Darby canine kidney (MDCK) cells. Live imaging shows that microspikes containing E-cadherin extend into gaps between E-cadherin clusters on neighboring cells, while reformation of cadherin clusters across the cell–cell boundary correlates with microspike withdrawal. We identify Arp2/3, EVL, and CRMP-1 as 3 actin assembly factors necessary for microspike formation. Depleting these factors from cells using RNA interference (RNAi) results in myosin II-dependent unzipping of cadherin adhesive bonds. Therefore, actin polymerization-dependent protrusive activity operates continuously at cadherin cell–cell junctions to keep them shut and to prevent myosin II-dependent contractility from tearing cadherin adhesive contacts apart.
Sex Differences in Intergenerational Transfer Risk of Major Depressive Disorder

Background The children of depressed parents are more likely to suffer from mental illness, particularly major depressive disorder (MDD). However, most data come from adolescent and young-adult populations, and published studies have reported inconsistent results regarding intergenerational transmission. Material/Methods We retrospectively investigated hospitalized depressed patients with positive family history (FHP) from 1 Jan 2008 to 31 Dec 2017 and analyzed the differences in sex distribution in the intergenerational transfer risk of major depressive disorder. Results We enrolled 528 patients with maternal or paternal positive FHP from a total of 4856 patients, and divided them into 4 groups: female patients with maternal FHP (FM: 220, 41.7%), female patients with paternal FHP (FP: 116, 22.0%), male patients with maternal FHP (MM: 96, 18.2%), and male patients with paternal FHP (MP: 96, 18.2%). In this study, 12.2% of hospitalized depressed patients had an FHP. The ratio of male: female patients with FHP was 2: 3. The ratio of male: female patients with maternal FHP was almost 1: 2. Analyses showed that the risk of depression in daughters was higher than in sons. Compared with children of depressed fathers, the children of depressed mothers were at higher risk of depression. Daughters and sons share an equal risk of depression with paternal FHP. Conclusions The results suggest a clear interaction of sex between patients and their depressed parents. Daughters of depressed mothers had the highest risk of suffering from depression compared with other offspring.
Innate immune priming in the absence of TAK1 drives RIPK1 kinase activity–independent pyroptosis, apoptosis, necroptosis, and inflammatory disease

In this issue, Malireddi et al. use a model of pathogen-induced priming and inhibition of TAK1 to demonstrate RIPK1 kinase activity–independent inflammasome activation and pyroptosis, apoptosis, and necroptosis that drive myeloid proliferation and sepsis in TAK1-deficient animals.
Preoperative N-Terminal Pro–B-Type Natriuretic Peptide and Cardiovascular Events After Noncardiac Surgery

Background Preliminary data suggest that preoperative N-terminal pro-B-type natriuretic peptide (NT-proBNP) may improve risk prediction in patients undergoing noncardiac surgery. Objective To determine whether preoperative NT-proBNP has additional predictive value beyond a clinical risk score for the composite of vascular death and myocardial injury after noncardiac surgery (MINS) within 30 days after surgery. Design Prospective cohort study. Setting 16 hospitals in 9 countries. Patients 10 402 patients aged 45 years or older having inpatient noncardiac surgery. Measurements All patients had NT-proBNP levels measured before surgery and troponin T levels measured daily for up to 3 days after surgery. Results In multivariable analyses, compared with preoperative NT-proBNP values less than 100 pg/mL (the reference group), those of 100 to less than 200 pg/mL, 200 to less than 1500 pg/mL, and 1500 pg/mL or greater were associated with adjusted hazard ratios of 2.27 (95% CI, 1.90 to 2.70), 3.63 (CI, 3.13 to 4.21), and 5.82 (CI, 4.81 to 7.05) and corresponding incidences of the primary outcome of 12.3% (226 of 1843), 20.8% (542 of 2608), and 37.5% (223 of 595), respectively. Adding NT-proBNP thresholds to clinical stratification (that is, the Revised Cardiac Risk Index [RCRI]) resulted in a net absolute reclassification improvement of 258 per 1000 patients. Preoperative NT-proBNP values were also statistically significantly associated with 30-day all-cause mortality (less than 100 pg/mL [incidence, 0.3%], 100 to less than 200 pg/mL [incidence, 0.7%], 200 to less than 1500 pg/mL [incidence, 1.4%], and 1500 pg/mL or greater [incidence, 4.0%]). Limitation External validation of the identified NT-proBNP thresholds in other cohorts would reinforce our findings. Conclusion Preoperative NT-proBNP is strongly associated with vascular death and MINS within 30 days after noncardiac surgery and improves cardiac risk prediction in addition to the RCRI. Primary Funding Source Canadian Institutes of Health Research.
Using species distribution models to predict potential hot-spots for Rift Valley Fever establishment in the United Kingdom

Vector borne diseases are a continuing global threat to both human and animal health. The ability of vectors such as mosquitos to cover large distances and cross country borders undetected provide an ever-present threat of pathogen spread. Many diseases can infect multiple vector species, such that even if the climate is not hospitable for an invasive species, indigenous species may be susceptible and capable of transmission such that one incursion event could lead to disease establishment in these species. Here we present a consensus modelling methodology to estimate the habitat suitability for presence of mosquito species in the UK deemed competent for Rift Valley fever virus (RVF) and demonstrate its application in an assessment of the relative risk of establishment of RVF virus in the UK livestock population. The consensus model utilises observed UK mosquito surveillance data, along with climatic and geographic prediction variables, to inform six independent species distribution models; the results of which are combined to produce a single prediction map. As a livestock host is needed to transmit RVF, we then combine the consensus model output with existing maps of sheep and cattle density to predict the areas of the UK where disease is most likely to establish in local mosquito populations. The model results suggest areas of high suitability for RVF competent mosquito species across the length and breadth of the UK. Notable areas of high suitability were the South West of England and coastal areas of Wales, the latter of which was subsequently predicted to be at higher risk for establishment of RVF due to higher livestock densities. This study demonstrates the applicability of outputs of species distribution models to help predict hot-spots for risk of disease establishment. While there is still uncertainty associated with the outputs we believe that the predictions are an improvement on just using the raw presence points from a database alone. The outputs can also be used as part of a multidisciplinary approach to inform risk based disease surveillance activities.
Non-sleepy obstructive sleep apnoea: to treat or not to treat?

Non-sleepy obstructive sleep apnoea (OSA) is thought to have a prevalence of around 20–25% in industrialised countries. However, the question of whether it should be routinely treated or not is controversial. This review collates the results from recent randomised controlled trials addressing OSA and examines whether treating the condition leads to improvements in quality of life and reduced cardiometabolic dysfunction, comorbidities generally attributed to untreated obstructive sleep apnoea/hypopnoea syndrome. Non-sleepy obstructive sleep apnoea: to treat or not to treat? http://bit.ly/2GaB7xp
Targeting pathological leak of ryanodine receptors: preclinical progress and the potential impact on treatments for cardiac arrhythmias and heart failure

ABSTRACT Introduction: Type-2 ryanodine receptor (RyR2) located on the sarcoplasmic reticulum initiate systolic Ca2+ transients within cardiomyocytes. Proper functioning of RyR2 is therefore crucial to the timing and force generated by cardiomyocytes within a healthy heart. Improper intracellular Ca2+ handing secondary to RyR2 dysfunction is associated with a variety of cardiac pathologies including catecholaminergic polymorphic ventricular tachycardia (CPVT), atrial fibrillation (AF), and heart failure (HF). Thus, RyR2 and its associated accessory proteins provide promising drug targets to scientists developing therapeutics for a variety of cardiac pathologies. Areas covered: In this article, we review the role of RyR2 in a variety of cardiac pathologies. We performed a literature search utilizing PubMed and MEDLINE as well as reviewed registries of trials from clinicaltrials.gov from 2010 to 2019 for novel therapeutic approaches that address the cellular mechanisms underlying CPVT, AF, and HF by specifically targeting defective RyR2 channels. Expert opinion: The negative impact of cardiac dysfunction on human health and medical economics are major motivating factors for establishing new and effective therapeutic approaches. Focusing on directly impacting the molecular mechanisms underlying defective Ca2+ handling by RyR2 in HF and arrhythmia has great potential to be translated into novel and innovative therapies.