Miracle-dz/UniFAR-FTUs huggingface dataset:
Differential Cleaving of Specific Substrates for Cathepsin-Like Activity Shows Cysteine and Serine Protease Activities and a Differential Profile Between Anisakis simplex s.s. and Anisakis pegreffii, Sibling Species Major Etiologic Agents of Anisakiasis.

Humans can contract anisakiasis by eating fish or squid containing live larvae of the third stage (L3) of the parasitic nematodes of the genus Anisakis, majorly from Anisakis simplex s.s. and Anisakis pegreffii, sibling species of the A. simplex s.l. complex. Most cases diagnosed molecularly are due to A. simplex s.s. , although A. pegreffii has also been identified in human cases. Cathepsins are mostly lysosomal multifunctional cysteine proteases and can participate in the pathogenicity of parasites. Cathepsin B and L activities were investigated in the two sibling species of Anisakis mentioned. L3 and L4 of both species were collected during their in vitro development, and cathepsin activity was determined in the range of pH 4.0-8.5, using specific fluorogenic substrates. The activity detected with the substrate Z-FR-AMC (N-α-benzyloxycarbonyl-L-phenylalanyl-L-arginine-7-amido-4-methyl-coumarin) was identified as cathepsin L (optimum pH = 5.0, range 4.0-6.0, p < 0.001). Activity was highest in L3 freshly collected from fish, especially in A. simplex s.s. , and decreased during development, which could be related to virulence, invasion of host tissues, and/or intracellular digestion. Cathepsin B-like activity was not identified with either of the substrates used (Z-RR-AMC [N-α-benzyloxycarbonyl-L-arginyl-L-arginine-7-amido-4-methyl-coumarin] and Z-FR-AMC). With Z-RR-AMC, cleaving activity was detected almost exclusively in L4 of A. simplex s.s. (p < 0.05) with optimum pH = 8.0 (range 7.0-8.5). Assays with class-specific protease inhibitors showed that this activity was mainly due to serine proteases [up to 90% inhibition with 4-(2-aminoethyl) benzenesulfonyl fluoride hydrochloride (AEBSF)], although metalloproteases (up to 40-45% inhibition with 1,10 phenanthroline) and slight cysteine protease activity (<15% inhibition with E64 [L-trans-epoxysuccinyl-leucylamido-(4-guanidino)-butane]; putative cathepsin B-like) were also detected. These results show differential serine protease activity between sibling Anisakis species, regulated by larval development, at least in A. simplex s.s. The higher cathepsin L and serine protease activities detected in this species could be related to its greater pathogenicity, reported in experimental animals, compared to that of A. pegreffii.
Metabolomics Studies on Cytoplasmic Male Sterility during Flower Bud Development in Soybean

Abnormal reactive oxygen species (ROS) may mediate cytoplasmic male sterility (CMS). To observe the effect of ROS on soybean CMS, metabolite content and antioxidant enzyme activity in the flower buds between soybean N8855-derived CMS line and its maintainer were compared. Of the 612 metabolites identified, a total of 74 metabolites were significantly differentiated in flower buds between CMS line and its maintainer. The differential metabolites involved 32 differential flavonoids, 13 differential phenolamides, and 1 differential oxidized glutathione (GSSG) belonging to a non-enzymatic ROS scavenging system. We observed lower levels of flavonoids and antioxidant enzyme activities in flower buds of the CMS line than in its maintainer. Our results suggest that deficiencies of enzymatic and non-enzymatic ROS scavenging systems in soybean CMS line cannot eliminate ROS in anthers effectively, excessive accumulation of ROS triggered programmed cell death and ultimately resulted in pollen abortion of soybean CMS line.
Left Ventricular Function and Cardiac Biomarker Release -The Influence of Exercise Intensity, Duration and Mode: A Systematic Review and Meta-Analysis

METHODS: Six undergraduate EXPH students completed a pre-intervention quiz which assessed knowledge of blood lactate production and lactate threshold. Participants received a lecture on lactate production and lactate threshold from an expert in the field of human performance and discussed peer-reviewed research readings. Supervised training and practice were held prior to conducting lactate threshold testing on the varsity women’s rowing team. Following, participants met to review physiological concepts, data collection procedures, discuss research readings, and reflect on the service component of the project. At the end of the project, participants completed the same lactate threshold quiz as well as an anonymous, online, 15-question self-efficacy and satisfaction survey with answer choices on a 7-point Likert scale. A focus group discussion moderated by trained researchers captured participants’ perceptions of the experiential service learning project. Data were content analyzed to identify common themes using independent data reviewers and a tiebreaker when necessary. RESULTS: All participants agreed or strongly agreed that participation in this project would allow them to make a difference in [their] community, enable them to interact with relevant professionals in ways that are meaningful and effective, and apply [their] knowledge in ways that solve real-life problems. All students strongly agreed they would recommend this experience to their friends. Compared with a pre-assessment, participants scored 10% higher on the lactate knowledge quiz at the end of the experiential learning project. Students reported improved selfefficacy, knowledge, communication, and confidence in exercise physiology related content as well as professional skills. CONCLUSION: An experiential learning project incorporating multiple teaching methodologies successfully improved knowledge, self-efficacy, and professional skills in human performance testing.
In Vitro Replication of Human Norovirus

Human norovirus (HuNoV) infection is a major cause of gastroenteritis all over the world. Despite this, these non-enveloped RNA viruses are poorly characterized due to the lack of robust and widely available HuNoV culture systems. The two published systems (B cell line and stem cell-derived enteroids) support replication of HuNoVs but the levels of replication are not sufficient for the generation of highly purified virus stocks or the development of culture-based quantification assays. Therefore, improvement of HuNoV in vitro replication is still needed. Murine norovirus and other caliciviruses have provided insights into norovirus replication that paved the way for the development of the current HuNoV culture systems and may also aid in the improvement of these systems. This review will highlight ways in which previous research guided and impacted the development of HuNoV culture systems and discuss ways in which more recent discoveries might be utilized to improve the quality of the HuNoV in vitro replication.
Paradigm merger in natural language processing

This chapter considers the revolution that has taken place in natural language processing research over the last ve years. It begins by providing a brief guide to the structure of the eld and then presents a caricature of two competing paradigms of 1980s NLP research and indicates the reasons why many of those involved have now seen t to abandon them in their pure forms. Attention is then directed to the lexicon, a component of NLP systems which started out as Cinderella but which has nally arrived at the ball. This brings us to an account of what has been going on in the eld most recently, namely a merging of the two 1980s paradigms in a way that is generating a host of interesting new research questions. The chapter concludes by trying to identify some of the key conceptual, empirical and formal issues that now stand in need of resolution.
In-Cold Exposure to Z-3-Hexenal Provides Protection Against Ongoing Cold Stress in Zea mays

Green leaf volatiles (GLVs), which have mostly been described as providers of protection against insect herbivory and necrotrophic pathogen infections, were recently shown to provide significant fortification against cold stress damage. It was further demonstrated that cold-damaged maize seedlings released a significant amount of GLVs, in particular, Z-3-hexenal (Z-3-HAL). Here, we report that the in-cold treatment of maize seedlings with Z-3-HAL significantly improved cold stress resistance. The transcripts for cold-protective genes were also significantly increased in the Z-3-HAL treated maize seedlings over those found in only cold stressed plants. Consequently, the maize seedlings treated with HAL during cold showed a significantly increased structural integrity, significantly less damage, and increased growth after cold stress, relative to the non-HAL treated maize seedlings. Together, these results demonstrate the protective effect of in-cold treatment with HAL against cold damage, and suggest that the perception of these compounds during cold episodes significantly improves resistance against this abiotic stress.
Hippocampal volume, cognitive functions, depression, anxiety, and quality of life in patients with Cushing's syndrome.

CONTEXT Cushing's syndrome (CS) is associated with hippocampal atrophy and psychopathology. Objective: The primary objective of this systematic review was to assess hippocampal volume in CS patients. The secondary objectives were to assess cognitive functioning, depressive-, and anxiety symptoms, and quality of life (QoL) in CS patients. DATA SOURCES PubMed, Embase, Cochrane, LILACs, and Scopus were searched for relevant studies until 1st of May 2019. STUDY SELECTION The current study includes either case-control studies comparing CS patients with healthy controls, or studies assessing CS patients before and after surgery. The initial search resulted in 18 studies fulfilling the inclusion criteria. DATA EXTRACTION Data extraction regarding all outcomes was performed independently by two reviewers. Quality assessment was assessed by using the Newcastle-Ottawa Scale for case-control studies. DATA SYNTHESIS Meta-analysis were performed using a random effect model. The right hippocampal volume in CS was reduced by 0·68 SMD (95% CI; -1·12 to -0·24; p=0·002; I2=0%) compared to healthy controls, but with no increase in hippocampal volume after surgery. CS patients presented with more depressive symptoms, impaired cognitive functions, and reduced health related QoL (HRQoL), which all responded favourably to surgery. The data did not support the presence of anxiety in CS patients. CONCLUSIONS The current study does not suggest an overall reduction of hippocampal volume in CS patients. However, most cognitive domains were significantly affected and responded favorably to surgery. Depressive symptoms as well as reduced HRQoL were present in CS patients and improved after surgery.
Oral treprostinil in transition or as add-on therapy in pediatric pulmonary arterial hypertension

Treprostinil, a prostacyclin analogue, is approved for the treatment of pulmonary arterial hypertension (PAH) in adults. Transition from parenteral to oral treprostinil has been successfully accomplished in adults with PAH but not in children. In this multicenter study, pediatric patients treated with parenteral (Cohort 1) or inhaled (Cohort 2) treprostinil were transitioned to oral treprostinil. Prostacyclin-naïve individuals on background oral PAH therapy received oral treprostinil as add-on therapy (Cohort 3). Successful transition was oral treprostinil dose maintenance through week 24. Patients were monitored for adverse events (AEs), 6-min walk distance (6MWD), PAH symptoms, World Health Organization (WHO) Functional Class (FC), cardiac magnetic resonance imaging (cMRI), cardiopulmonary exercise testing (CPET), and quality of life through 24 weeks. A total of 32 patients were enrolled in the study; 23 (72%) were girls (mean age = 12.2 years). All patients were on background oral PAH therapy. Overall, patients (96.9%) maintained transition to oral treprostinil; one patient (Cohort 1) transitioned to oral treprostinil, then back to parenteral after experiencing syncope and WHO FC change from II to III. Cohorts 1, 2, and 3 received a final mean oral treprostinil dose of 5.6, 3.3, and 4.5 mg t.i. d. , respectively. All cohorts had variable changes in 6MWD, cMRI, and CPET. Overall, 12 serious AEs were reported. All patients had drug-related AEs including headache (81%), diarrhea (69%), nausea (66%), vomiting (66%), and flushing (56%). Pediatric patients maintained transition to oral treprostinil with preservation of exercise capacity and WHO FC. Prostanoid-related AEs were most common and similar to those reported in adults.
Vitamin D Supplementation and Cardiovascular Disease Risks in More Than 83 000 Individuals in 21 Randomized Clinical Trials: A Meta-analysis.

Importance Observational studies have reported an association between low serum vitamin D levels and elevated risk of cardiovascular disease (CVD) events, but such studies cannot prove causation because of possible unmeasured confounding. Objective We conducted a meta-analysis of randomized clinical trials that tested the association of vitamin D supplementation with reduced CVD events and all-cause mortality. Data Sources Literature search through PubMed, the Cochrane Library, and Embase was completed by 2 reviewers from each database's inception to December 15, 2018. Study Selection Inclusion criteria were randomized clinical trials that reported the effect of long-term (≥1 year) vitamin D supplementation on CVD events and all-cause mortality. Studies that did not include cardiovascular outcomes were excluded. Data Extraction and Synthesis Data were abstracted independently by 2 authors. Random-effects models were used to report the risk ratios (RRs) and 95% CIs. Main Outcomes and Measures Major adverse cardiovascular events was the primary outcome, and rates of myocardial infarction, stroke or cerebrovascular accident, CVD mortality, and all-cause mortality were the secondary end points. Results Twenty-one randomized clinical trials were included (including 83 291 patients, of whom 41 669 received vitamin D and 41 622 received placebos). The mean (SD) age of trial participants was 65.8 (8.4) years; 61 943 (74.4%) were female. Only 4 trials had prespecified CVD as a primary end point. Vitamin D supplementation compared with placebo was not associated with reduced major adverse cardiovascular events (RR, 1.00 [95% CI, 0.95-1.06]; P = .85) nor the secondary end points of myocardial infarction (RR, 1.00 [95% CI, 0.93-1.08]; P = .92), stroke (RR, 1.06 [95% CI, 0.98-1.15]; P = .16), CVD mortality (RR, 0.98 [95% CI, 0.90-1.07]; P = .68), or all-cause mortality (RR, 0.97 [95% CI, 0.93-1.02]; P = .23). Results were generally consistent by sex, baseline 25-hydroxyvitamin D level, vitamin D dosage, formulation (daily vs bolus dosing), and presence or absence of concurrent calcium administration. Conclusions and Relevance In this updated meta-analysis, vitamin D supplementation was not associated with reduced major adverse cardiovascular events, individual CVD end points (myocardial infarction, stroke, CVD mortality), or all-cause mortality. The findings suggest that vitamin D supplementation does not confer cardiovascular protection and is not indicated for this purpose.
The role of integrins in the pathogenesis of inflammatory bowel disease: Approved and investigational anti‐integrin therapies

Inflammatory bowel disease (IBD) is characterized by uncontrolled inflammation in the gastrointestinal tract. The underlying pathobiology of IBD includes an increase in infiltrating gut‐homing lymphocytes. Although lymphocyte homing is typically a tightly regulated and stepwise process involving multiple integrins and adhesion molecules expressed on endothelial cells, the distinct roles of integrin‐expressing immune cells is not fully understood in the pathology of IBD. In this review, we detail the involvement of integrins expressed on specific lymphocyte subsets in the pathogenesis of IBD and discuss the current status of approved and investigational integrin‐targeted therapies.
Recovery of contralesional saccade choice and reaction time deficits after a unilateral endothelin-1-induced lesion in the macaque caudal prefrontal cortex.

The caudal primate prefrontal cortex (PFC) is involved in target selection and visually-guided saccades through both covert attention and overt orienting eye movements (Passingham and Wise 2012). Unilateral damage to the caudal PFC often leads to decreased awareness of a contralesional target alone, referred to as 'neglect', or when it is presented simultaneously with an ipsilesional target, referred to as 'extinction'. Here, we examined whether deficits in contralesional target selection were due to contralesional oculomotor deficits, such as slower reaction times. We experimentally-induced a focal ischemic lesion in the right caudal PFC of four male macaque monkeys using the vasoconstrictor endothelin-1 and measured saccade choice and reaction times on double stimulus free-choice and single stimulus trials before and after the lesion. We found that (1) endothelin-1-induced lesions in the caudal PFC produced contralesional target selection deficits that varied in severity and duration based on lesion volume and location; (2) contralesional neglect-like deficits were transient and recovered by week 4 post-lesion; (3) contralesional extinction-like deficits were longer lasting and recovered by weeks 8-16 post-lesion; (4) contralesional reaction time returned to baseline well before the contralesional choice deficit had recovered; and (5) neither the mean reaction times or the reaction time distributions could account for the degree of contralesional extinction on the free-choice task throughout recovery. These findings demonstrate that the saccade choice bias observed after a right caudal PFC lesion is not exclusively due to contralesional motor deficits but instead reflects a combination of impaired motor and attentional processing.
Early Versus Delayed Stroke After Cardiac Surgery: A Systematic Review and Meta‐Analysis

Background Although it is traditionally regarded as a single entity, perioperative stroke comprises 2 separate phenomena (early/intraoperative and delayed/postoperative stroke). We aimed to systematically evaluate incidence, risk factors, and clinical outcome of early and delayed stroke after cardiac surgery. Methods and Results A systematic review (MEDLINE, EMBASE, Cochrane Library) was performed to identify all articles reporting early (on awakening from anesthesia) and delayed (after normal awakening from anesthesia) stroke after cardiac surgery. End points were pooled event rates of stroke and operative mortality and incident rate of late mortality. Thirty‐six articles were included (174 969 patients). The pooled event rate for early stroke was 0.98% (95% CI 0.79% to 1.23%) and was 0.93% for delayed stoke (95% CI 0.77% to 1.11%; P=0.68). The pooled event rate of operative mortality was 28.8% (95% CI 17.6% to 43.4%) for early and 17.9% (95% CI 14.0% to 22.7%) for delayed stroke, compared with 2.4% (95% CI 1.9% to 3.1%) for patients without stroke (P<0.001 for early versus delayed, and for perioperative stroke, early stroke, and delayed stroke versus no stroke). At a mean follow‐up of 8.25 years, the incident rate of late mortality was 11.7% (95% CI 7.5% to 18.3%) for early and 9.4% (95% CI 5.9% to 14.9%) for delayed stroke, compared with 3.4% (95% CI 2.4% to 4.8%) in patients with no stroke. Meta‐regression demonstrated that off‐pump was inversely associated with early stroke (β=−0.009, P=0.01), whereas previous stroke (β=0.02, P<0.001) was associated with delayed stroke. Conclusions Early and delayed stroke after cardiac surgery have different risk factors and impacts on operative mortality as well as on long‐term survival.
A Multifaceted Intervention Improves Prescribing for Acute Respiratory Infection for Adults and Children in Emergency Department and Urgent Care Settings.

BACKGROUND Antibiotics are commonly prescribed during emergency department (ED) and urgent care center (UCC) visits for viral acute respiratory infection (ARI). We evaluate the comparative effectiveness of an antibiotic stewardship intervention adapted for acute care ambulatory settings (adapted intervention) to a stewardship intervention that additionally incorporates behavioral nudges (enhanced intervention) in reducing inappropriate prescriptions. METHODS This study was a pragmatic, cluster-randomized clinical trial conducted in three academic health systems comprising five adult and pediatric EDs and four UCCs. Randomization of the nine sites was stratified by health system; all providers at each site received either the adapted or the enhanced intervention. The main outcome was the proportion of antibiotic-inappropriate ARI diagnosis visits that received an outpatient antibiotic prescription by individual providers. We estimated a hierarchical mixed-effects logistic regression model comparing visits during the influenza season for 2016 to 2017 (baseline) and 2017 to 2018 (intervention). RESULTS There were 44,820 ARI visits among 292 providers across all nine cluster sites. Antibiotic prescribing for ARI visits dropped from 6.2% (95% confidence interval [CI] = 4.5% to 7.9%) to 2.4% (95% CI = 1.3% to 3.4%) during the study period. We found a significant reduction in inappropriate prescribing after adjusting for health-system and provider-level effects from 2.2% (95% CI = 1.0% to 3.4%) to 1.5% (95% CI = 0.7% to 2.3%) with an odds ratio of 0.67 (95% CI = 0.54 to 0.82). Difference-in-differences between the two interventions was not significantly different. CONCLUSION Implementation of antibiotic stewardship for ARI is feasible and effective in the ED and UCC settings. More intensive behavioral nudging methods were not more effective in high-performance settings.
Assessment and treatment of high-risk challenging behavior of adolescents with autism in an aquatic setting.

Aquatic-based activities produce positive skill and health benefits for individuals with Autism Spectrum Disorder (ASD); however, aquatic contexts, such as the pool, introduce the risk of injury and drowning. This risk is heightened when individuals with ASD engage in challenging behavior in the pool context. The purpose of the study was to evaluate the effects of differential reinforcement without extinction for 2 participants diagnosed with ASD who engaged in challenging behavior when asked to transition from the pool. The treatment successfully decreased participants' transition latencies and challenging behavior during transitions from the pool for up to 2 months following treatment. Lifeguard staff rated the procedures as highly acceptable and helpful, and noted high degrees of satisfaction with improvements for each participant's behavior.
Correlated states in balanced neuronal networks.

Understanding the magnitude and structure of interneuronal correlations and their relationship to synaptic connectivity structure is an important and difficult problem in computational neuroscience. Early studies show that neuronal network models with excitatory-inhibitory balance naturally create very weak spike train correlations, defining the "asynchronous state. " Later work showed that, under some connectivity structures, balanced networks can produce larger correlations between some neuron pairs, even when the average correlation is very small. All of these previous studies assume that the local network receives feedforward synaptic input from a population of uncorrelated spike trains. We show that when spike trains providing feedforward input are correlated, the downstream recurrent network produces much larger correlations. We provide an in-depth analysis of the resulting "correlated state" in balanced networks and show that, unlike the asynchronous state, it produces a tight excitatory-inhibitory balance consistent with in vivo cortical recordings.