Miracle-dz/UniFAR-FTUs huggingface dataset:
The outcome of thrombolytic therapy for acute ischemic stroke after extended treatment from 3 to 4.5 hours in Maharaj Nakorn Chiang Mai Hospital

Objective To present the outcome of acute ischemic stroke patients given thrombolytic therapy from 3 to 4.5 hours after the onset of symptoms. Methods All acute ischemic stroke (AIS) patients admitted to the Stroke Unit at Maharaj Nakorn Chiang Mai Hospital, Chiang Mai, Thailand and treated with tissue plasminogen activator (rtPA) between January 1, 2013, and December 31, 2013, were chart reviewed retrospectively. The recovery rate and complications were compared between patients treated within 3 hours and from 3 to 4.5 hours after the onset of symptoms (group A and B, respectively), as was the outcome between patients in Group B and those in Western trials. Results Ninety two AIS patients were treated with rtPA during the study period, with 68.48% and 31.52% of them being treated in Group A and B, respectively. Only the rate of neurological improvement was signifi cantly different at 24 hours between each group (55.0% vs 27.6%, p =0.03). There was no difference in favorable outcome at 3 months, including the rate of complete recovery (33.3% vs 51.7%, p =0.23) and functional independence (50.7% vs 58.6%, p =0.24). The complication of symptomatic intracranial hemorrhage (1.5% vs 3.4%, p =0.57) and mortality rate (at admission, 3.1% vs 10.3%, p =0.54 and at 3 months, 7.9% vs 10.3%, p =0.54) was similar. The outcome of patients treated in Group B was comparable to that from Western trials. Conclusion The outcome of patients treated in group B was comparable to that for patients treated in group A. The results of this study confirmed that the window of opportunity for rtPA treatment can extend to 4.5 hours. However, early rather than later treatment had a better outcome.
Coronary Calcium Risk Score and Cardiovascular Risk.

The association between presence of coronary artery calcium (CAC) and risk of coronary artery disease (CAD) has been appreciated for decades. In this review, we critically appraise the role of CAC based on computerized tomography in contemporary risk stratification. Available evidence suggests that measurement of CAC is a useful modality in many patients for more precise risk stratification and prognostic determination. Whether newer CAC score incorporating extra coronary calcification, will add incremental value, especially for stroke and other non-coronary vascular outcomes needs prospective study.
Can We Predict the Pressure Induced Phase Transition of Urea? Application of Quantum Molecular Dynamics

Crystalline urea undergoes polymorphic phase transition induced by high pressure. Form I, which is the most stable form at normal conditions and Form IV, which is the most stable form at 3.10 GPa, not only crystallize in various crystal systems but also differ significantly in the unit cell dimensions. The aim of this study was to determine if it is possible to predict polymorphic phase transitions by optimizing Form I at high pressure and Form IV at low pressure. To achieve this aim, a large number of periodic density functional theory (DFT) calculations were performed using CASTEP. After geometry optimization of Form IV at 0 GPa Form I was obtained, performing energy minimization of Form I at high pressure did not result in Form IV. However, employing quantum molecular isothermal–isobaric (NPT) dynamics calculations enabled to accurately predict this high-pressure transformation. This study shows the potential of different approaches in predicting the polymorphic phase transition and points to the key factors that are necessary to achieve the success.
Accumulated Disadvantage over the Lower Secondary School Years in Helsinki Metropolitan Area, Finland

Accumulated disadvantage (AD) is conceptualised here as an agglomeration of unfavourable or prejudicial conditions which in adolescence may compromise the progress to further education or future life chances. There are several theories on AD, suggesting, e.g., (1) an increase of AD by age and (2) trajectories (previous disadvantage predicts later disadvantage). Social pathways theory suggests that (3) a third factor (e.g., socioeconomic position, SEP) mediates or moderates the association between early and later disadvantage, while other theories imply (4) polarisation (a strengthening association between AD and SEP by age) or (5) equalisation (a weakening of association between AD and SEP). We apply these theories to longitudinal data of 7th graders (13 years, N = 5742), followed until the end of the 9th grade. Five dimensions of disadvantage were health (poor self-rated health), social behaviour (poor prosocial behaviour), normative (conduct disorders), educational (poor academic achievement), and economic (parental unemployment). The results show that the prevalence of AD increased over the follow-up as most indicators of disadvantage elevated. AD at the 7th grade predicted later AD, as did the SEP of the students. Moderation of AD by SEP was also observed. The study corroborates with hypotheses on increase of AD, trajectory, and social pathways but no signs of polarisation or equalisation were observed.
Is the middle cranial fossa a reliable predictor of temporal lobe volume in extant and fossil anthropoids?

OBJECTIVES We investigate the suitability of middle cranial fossa (MCF) size as a proxy for temporal lobe volume (TLV), examining the strength of the association between TLV and MCF metrics and assess the reliability predicting TLV in fossil anthropoids. The temporal lobe of the primate brain is a multimodal association cortex involved in long-term memory, auditory, and visual processing with unique specializations in modern humans for language comprehension. The MCF is the bony counterpart for the temporal lobe providing inferences for fossil hominin temporal lobe evolution. We now investigate whether the MCF is a suitable proxy for the temporal lobe. METHODS A sample of 23 anthropoid species (n = 232, including 13 fossil species) from computed tomography (CT) scans of ex vivo crania and magnetic resonance imaging (MRI) of the in vivo brain were generated into three-dimensional (3D) virtual models. Seven linear metrics were digitally measured on the right MCF with right TLV calculated from in vivo MRI. RESULTS Regression analyses produced statistically significant correlations between TLV and all MCF metrics (r ≥ 0.85; p ≤ 0.0009) with TLV predictions within ±1 standard error and three MCF metrics (posterior-width, mid-length, and mid-width) the most reliable predictors of TLV with only one metric weakly associated with TLV. DISCUSSION These findings indicate a strong association between the MCF and TLV, provide reliable predictors of fossil TLV that were previously unattainable, allow the inclusion of fragmentary fossil material, and enable inferences into the emergence of modern human temporal lobe morphology.
Risk of mortality and cardiopulmonary arrest in critical patients presenting to the emergency department using machine learning and natural language processing

Emergency department triage is the first point in time when a patient’s acuity level is determined. The time to assign a priority at triage is short and it is vital to accurately stratify patients at this stage, since under-triage can lead to increased morbidity, mortality and costs. Our aim was to present a model that can assist healthcare professionals in triage decision making, namely in the stratification of patients through the risk prediction of a composite critical outcome—mortality and cardiopulmonary arrest. Our study cohort consisted of 235826 adult patients triaged at a Portuguese Emergency Department from 2012 to 2016. Patients were assigned to emergent, very urgent or urgent priorities of the Manchester Triage System (MTS). Demographics, clinical variables routinely collected at triage and the patients’ chief complaint were used. Logistic regression, random forests and extreme gradient boosting were developed using all available variables. The term frequency–inverse document frequency (TF-IDF) natural language processing weighting factor was applied to vectorize the chief complaint. Stratified random sampling was used to split the data into train (70%) and test (30%) data sets. Ten-fold cross validation was performed in train to optimize model hyper-parameters. The performance obtained with the best model was compared against the reference model—a regularized logistic regression trained using only triage priorities. Extreme gradient boosting exhibited good calibration properties and yielded areas under the receiver operating characteristic and precision-recall curves of 0.96 (95% CI 0.95-0.97) and 0.31 (95% CI 0.26-0.36), respectively. The predictors ranked with higher importance by this model were the Glasgow coma score, the patients’ age, pulse oximetry and arrival mode. Compared to the reference, the extreme gradient boosting model using clinical variables and the chief complaint presented higher recall for patients assigned MTS-3 and can identify those who are at risk of the composite outcome.
Peroxiredoxin 4 attenuates glutamate-induced neuronal cell death through inhibition of endoplasmic reticulum stress

Abstract High concentrations of glutamate induce neurotoxicity by eliciting reactive oxygen species (ROS) generation and intracellular Ca2+ influx. The disruption of Ca2+ homeostasis in the endoplasmic reticulum (ER) evokes ER stress, ultimately resulting in neuronal dysfunction. Additionally, glutamate participates in the development of neurodegenerative diseases, such as Alzheimer’s and Parkinson’s diseases. Peroxiredoxins (Prxs) are members of a family of antioxidant enzymes that protect cells from neurotoxic factor-induced apoptosis by scavenging hydrogen peroxide (H2O2). Prx4 is located in the ER and controls the redox condition within the ER. The present study investigated the protective effects of Prx4 against glutamate-induced neurotoxicity linked to ER stress. HT22 cells in which Prx4 was either overexpressed or silenced were used to elucidate the protective role of Prx4 against glutamate toxicity. The expression of Prx4 in HT22 cells was significantly increased in response to glutamate treatment, while ROS scavengers and ER chemical chaperones reduced Prx4 levels. Moreover, Prx4 overexpression reduces glutamate-induced apoptosis of HT22 cells by inhibiting ROS formation, Ca2+ influx, and ER stress. Therefore, we conclude that Prx4 has protective effects against glutamate-induced HT22 cell damage. Collectively, these results suggest that Prx4 could contribute to the treatment of neuronal disorders. Graphical Abstract
Dietary determinants of unhealthy metabolic phenotype in normal weight and overweight/obese adults: results of a prospective study

Abstract We aimed to investigate associations of dietary intakes with unhealthy metabolic phenotype development, in normal weight and overweight/obese adults separately. A total of 1114 individuals, aged ≥19 years, with healthy phenotype in the third examination cycle of Tehran Lipid and Glucose Study were followed until the fifth examination. Dietary intakes were estimated using the food frequency questionnaires, collected during the study. The participants were grouped as normal weight and overweight/obese according to the baseline body mass index (BMI). Unhealthy metabolic status was determined as having more than one component of metabolic syndrome using the Joint Interim Statement. Regardless of BMI, higher intakes of magnesium, dairy products, poultry, apples/pears, citrus fruits, and tea/coffee decreased the risk of developing unhealthy phenotype, while higher intakes of fast foods, organ meats, and potatoes increased the risk. Food intake can influence the transition to unhealthy phenotype in metabolically healthy adults, irrespective of the BMI status.
Exercising before a nap benefits memory better than napping or exercising alone.

Sleep leads to the enhancement of memory, and physical exercise also improves memory along with beneficial effects on sleep quality. Potentially, sleep and exercise may operate independently upon memory; alternatively, they may operate synergistically to boost memory above and beyond exercise or sleep alone. We tested this hypothesis in 115 young healthy adults (23±3.9 years) randomly allocated to one of the four conditions in a 2 (exercise vs no exercise) x 2 (nap vs no nap) design. The exercise intervention consisted of a 40-min, moderate-intensity cycling, while the no exercise condition was an equivalent period of rest. This was followed by a learning session in which participants memorized a set of 45 neutral pictures for a later test. Subsequently, participants were exposed to either a 60-min sleep period (nap) or an equivalent time of resting wakefulness, followed by a visual recognition test. We found a significant interaction between the effects of exercise and nap (p=0.014, ηp2 = 0.053), without significant main effects of exercise or nap conditions. Participants who experienced both exercise plus nap were significantly more accurate (83.8±2.9) than those who only napped (81.1±5.4, p=0.027) and those who only exercised (78.6±10.3, p=0.012). Within the combined nap plus exercise group, higher recognition accuracies were associated with higher sleep spindle densities (r = 0.46, p=0.015). Our results demonstrate that short-term exercise and a nap improve recognition memory over a nap or exercise alone. Exercise and sleep are not independent factors operating separately upon memory but work together to enhance long-term memory.
The Influence of Anaesthetic Drugs on the Laryngeal Motion in Dogs: A Systematic Review

Simple Summary Laryngeal paralysis is secondary to a loss of normal function of the larynx. Older dogs are particularly affected, with normal breathing becoming difficult. A successful diagnosis typically relies on the visualisation of either, complete, or partially absent, laryngeal movements. The use of anaesthesia drugs to provide sedation and stress relief is most commonly necessary during the diagnosis of laryngeal paralysis. While, the excessive administration of anaesthesia drugs may result in absent movements, the ideal anaesthesia regime remains unknown, and the use of sedation is questionable, given the potential for absent laryngeal movements, even in healthy dogs. In this systematic review, we found a potential benefit from using sedation during the evaluation of laryngeal function when compared to injectable anaesthetics only. The respiratory stimulant doxapram was effective in differentiating normal dogs from dogs with laryngeal paralysis but has associated safety hazards. Abstract Anaesthetic drugs are commonly used during the evaluation of laryngeal function in dogs. The aim of this review was to systematically analyse the literature describing the effects of anaesthetic drugs and doxapram on laryngeal motion in dogs and to determine which drug regime provides the best conditions for laryngeal examination. PubMed, Google Scholar, and EMBASE databases were used for the literature search up to November 2019. Relevant search terms included laryngeal motion, anaesthetic drugs and dogs. Studies were scored based on their level of evidence (LoE), according to the Oxford Centre for Evidence-based Medicine, and the quality was assessed using the risk-of-bias tool and SIGN-checklist. In healthy dogs, premedication before laryngeal examination provided better examination conditions and maintained overall adequate laryngeal motion in 83% of the studies. No difference in laryngeal motion between induction drugs was found in 73% of the studies but the effects in dogs with laryngeal paralysis remain largely unknown. Doxapram increased laryngeal motion in healthy dogs without serious side effects, but intubation was necessary for some dogs with laryngeal paralysis. Methodological characteristics varied considerably between studies, including the technique and timing of evaluation, number of assessors, study design, drug dose, combinations, route and speed of administration.
Dynamic capillary stalls in reperfused ischemic penumbra contribute to injury: A hyperacute role for neutrophils in persistent traffic jams

Ever since the introduction of thrombolysis and the subsequent expansion of endovascular treatments for acute ischemic stroke, it remains to be identified why the actual outcomes are less favorable despite recanalization. Here, by high spatio-temporal resolution imaging of capillary circulation in mice, we introduce the pathological phenomenon of dynamic flow stalls in cerebral capillaries, occurring persistently in salvageable penumbra after reperfusion. These stalls, which are different from permanent cellular plugs of no-reflow, were temporarily and repetitively occurring in the capillary network, impairing the overall circulation like small focal traffic jams. In vivo microscopy in the ischemic penumbra revealed leukocytes traveling slowly through capillary lumen or getting stuck, while red blood cell flow was being disturbed in the neighboring segments under reperfused conditions. Stall dynamics could be modulated, by injection of an anti-Ly6G antibody specifically targeting neutrophils. Decreased number and duration of stalls were associated with improvement in penumbral blood flow within 2–24 h after reperfusion along with increased capillary oxygenation, decreased cellular damage and improved functional outcome. Thereby, dynamic microcirculatory stall phenomenon can be a contributing factor to ongoing penumbral injury and is a potential hyperacute mechanism adding on previous observations of detrimental effects of activated neutrophils in ischemic stroke.
Self-efficacy and empathy development through interprofessional student hotspotting

ABSTRACT In the United States, similar to other high-income countries, patients with complex health and social needs comprise a disproportionate amount of healthcare costs. Despite their frequent inpatient and emergency room usage, these patients receive ineffective care for their medical, social and behavioral needs, which often result from social determinants of health (SDoH). As the international dialogue on the importance of SDoH on health outcomes peaks, innovative strategies for teaching learners how to deliver care to patients with complex health and social needs has emerged as a top priority for health professions training programs. Student hotspotting, in which interprofessional student teams provide personalized, hands-on, intensive team-based interventions largely targeting the SDoH to patients with complex health and social needs, is one such program. We conducted a 7-month pilot study to explore whether students who participated in student hotspotting experienced an increase in their knowledge of, comfort working with, and empathy toward medically and socially complex patients. Preliminary results indicate that student participants exhibit greater self-efficacy and empathy than a control group of nonparticipating students, with the gap in the latter widening over time. While further study is warranted given limitations in the sample size and from attrition, this pilot study suggests that student hotspotting may be an effective way to better prepare our healthcare workforce to provide patient-centered, team-based care to patients with complex health and social needs and to reduce healthcare expenditures.
Unbiased Proteomic Approach Identifies Pathobiological Profiles in the Brains of Preclinical Models of Repetitive Mild Traumatic Brain Injury, Tauopathy, and Amyloidosis

No concerted investigation has been conducted to explore overlapping and distinct pathobiological mechanisms between repetitive mild traumatic brain injury (r-mTBI) and tau/amyloid proteinopathies considering the long history of association between TBI and Alzheimer’s disease. We address this problem by using unbiased proteomic approaches to generate detailed time-dependent brain molecular profiles of response to repetitive mTBI in C57BL/6 mice and in mouse models of amyloidosis (with amyloid precursor protein KM670/671NL (Swedish) and Presenilin 1 M146L mutations [PSAPP]) and tauopathy (hTau). Brain tissues from animals were collected at different timepoints after injuries (24 hr–12 months post-injury) and at different ages for tau or amyloid transgenic models (3, 9, and 15 months old), encompassing the pre-, peri-, and post-“onset” of cognitive and pathological phenotypes. We identified 30 hippocampal and 47 cortical proteins that were significantly modulated over time in the r-mTBI compared with sham mice. These proteins identified TBI-dependent modulation of phosphatidylinositol-3-kinase/AKT signaling, protein kinase A signaling, and PPARα/RXRα activation in the hippocampus and protein kinase A signaling, gonadotropin-releasing hormone signaling, and B cell receptor signaling in the cortex. Previously published neuropathological studies of our mTBI model showed a lack of amyloid and tau pathology. In PSAPP mice, we identified 19 proteins significantly changing in the cortex and only 7 proteins in hTau mice versus wild-type littermates. When we explored the overlap between our r-mTBI model and the PSAPP/hTau models, a fairly small coincidental change was observed involving only eight significantly regulated proteins. This work suggests a very distinct TBI neurodegeneration and also that other factors are needed to drive pathologies such as amyloidosis and tauopathy postinjury.
Estrogen Receptor Involvement in Noradrenergic Regulation of Ventromedial Hypothalamic Nucleus Glucoregulatory Neurotransmitter and Stimulus-Specific Glycogen Phosphorylase Enzyme Isoform Expression

Norepinephrine (NE) directly regulates ventromedial hypothalamic nucleus (VMN) glucoregulatory neurons and also controls glycogen-derived fuel provision to those cells. VMN nitric oxide (NO) and γ-aminobutyric acid (GABA) neurons and astrocytes express estrogen receptor-alpha (ERα) and ER-beta (ERβ) proteins. Current research used selective ERα (1,3Bis(4-hydroxyphenyl)-4-methyl-5-[4-(2-piperidinylethoxy)phenol]-1H-pyrazole dihydrochloride) or ERβ (4-[2-phenyl-5,7-bis(trifluoromethyl)pyrazolo[1,5-a]pyrimidin-3-yl]phenol) antagonists to address the premise that these ERs govern basal and/or NE-associated patterns of VMN metabolic neuron signaling and astrocyte glycogen metabolism. Both ERs stimulate expression of the enzyme marker protein neuronal nitric oxide synthase, not glutamate decarboxylase65/67. NE inhibition or augmentation of neuronal nitric oxide synthase and glutamate decarboxylase65/67 profiles was ER-independent or -dependent, respectively. In both neuron types, VMN ERβ activity inhibited baseline alpha1- (α1-) and/or alpha2- (α2-)adrenergic receptor (AR) expression, but ERα and -β signaling was paradoxically crucial for noradrenergic upregulation of α2-AR. NE inhibited glycogen synthase expression and exerted opposite effects on VMN adenosine monophosphate-sensitive glycogen phosphorylase (GP)-brain type (stimulatory) versus NE-sensitive GP muscle (inhibitory) via ERα or -β activity. Results document unique ERα and ERβ actions on metabolic transmitter and AR protein expression in VMN nitrergic versus GABAergic neurons. ER effects varied in the presence versus absence of NE, indicating that both neuron types are substrates for estradiol and noradrenergic regulatory interaction. NE-dependent ER control of VMN GP variant expression implies that these signals also act on astrocytes to direct physiological stimulus-specific control of glycogen metabolism, which may in turn influence GABA transmission.