Miracle-dz/UniFAR-FTUs huggingface dataset:
Comparison of Molecular and In Silico Salmonella Serotyping for Salmonella Surveillance

Salmonella surveillance and outbreak management is a key function of public health. Laboratories are shifting from antigenic serotype determination to molecular methods including microarray or whole genome sequencing technologies. The objective of this study was to compare the Check&Trace Salmonella™ DNA microarray (CTS), a commercially available assay with the Salmonella in silico typing resource (SISTR), which uses whole genome sequencing technology for serotyping clinical Salmonella strains in Alberta, Canada, collected over an 18-month period. A high proportion of isolates (96.3%) were successfully typed by both systems. SISTR is a powerful tool for laboratories which already have a WGS infrastructure in place, whereas smaller laboratories can benefit from a commercial microarray system and reduce the processing cost per isolate compared to traditional serotyping.
Incidental T2 hyperintensities in the medial part of the bilateral globus pallidus are possibly an age-related physiological finding

Background and purpose Bilateral T2 hyperintensities in the medial part of the globus pallidus (GP) are sometimes incidentally observed in patients without a known history of diseases that present with such lesions. The purpose of this study was to evaluate the frequency of this finding and the association between this finding and age, lifestyle diseases and GP calcification. Methods We retrospectively investigated the brain magnetic resonance imaging (MRI) of 742 patients, which included between 104 and 108 consecutive patients from each decade of life between the 20s and 80s. The signal intensity ratio of the medial part to the lateral part of the GP in T2-weighted images (T2 medial/lateral ratio) was evaluated. For cases in which brain computed tomography images were available (N=437), GP calcifications were also evaluated. The associations between the T2 medial/lateral ratio and age, sex, history of lifestyle diseases and GP calcification were investigated. Results Bilateral T2 medial/lateral ratios >1.10, 1.30 and 1.50 were observed in 29.8%, 7.1% and 1.8% of all cases, respectively. A high bilateral T2 medial/lateral ratio was observed less frequently in young patients (p<0.01), more frequently in elderly patients and those with hypertension or dyslipidaemia (p<0.05) and more frequently in patients with a calcified GP (p<0.01). Conclusion Incidental bilateral T2 hyperintensities in the medial part of the GP on brain MRI are most likely an age-related physiological finding.
Impact of Obesity-Induced Inflammation on Cardiovascular Diseases (CVD)

Overweight and obesity are key risk factors of cardiovascular disease (CVD). Obesity is currently presented as a pro-inflammatory state with an expansion in the outflow of inflammatory cytokines, such as interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α), alongside the expanded emission of leptin. The present review aimed to evaluate the relationship between obesity and inflammation and their impacts on the development of cardiovascular disease. A literature search was conducted by employing three academic databases, namely PubMed (Medline), Scopus (EMBASE), and the Cumulative Index to Nursing and Allied Health Literature (CINAHL). The search presented 786 items, and by inclusion and exclusion filterers, 59 works were considered for final review. The Newcastle–Ottawa Scale (NOS) method was adopted to conduct quality assessment; 19 papers were further selected based on the quality score. Obesity-related inflammation leads to a low-grade inflammatory state in organisms by upregulating pro-inflammatory markers and downregulating anti-inflammatory cytokines, thereby contributing to cardiovascular disease pathogenesis. Because of inflammatory and infectious symptoms, adipocytes appear to instigate articulation and discharge a few intense stage reactants and carriers of inflammation. Obesity and inflammatory markers are strongly associated, and are important factors in the development of CVD. Hence, weight management can help prevent cardiovascular risks and poor outcomes by inhibiting inflammatory mechanisms.
The Unfolded Protein Response: An Overview

Simple Summary The unfolded protein response (UPR) is the cells’ way of maintaining the balance of protein folding in the endoplasmic reticulum, which is the section of the cell designated for folding proteins with specific destinations such as other organelles or to be secreted by the cell. The UPR is activated when unfolded proteins accumulate in the endoplasmic reticulum. This accumulation puts a greater load on the molecules in charge of folding the proteins, and therefore the UPR works to balance this by lowering the number of unfolded proteins present in the cell. This is done in multiple ways, such as lowering the number of proteins that need to be folded; increasing the folding ability of the endoplasmic reticulum and by removing some of the unfolded proteins which take longer to fold. If the UPR is successful at reducing the number of unfolded proteins, the UPR is inactivated and the cells protein folding balance is returned to normal. However, if the UPR is unsuccessful, then this can lead to cell death. Abstract The unfolded protein response is the mechanism by which cells control endoplasmic reticulum (ER) protein homeostasis. Under normal conditions, the UPR is not activated; however, under certain stresses, such as hypoxia or altered glycosylation, the UPR can be activated due to an accumulation of unfolded proteins. The activation of the UPR involves three signaling pathways, IRE1, PERK and ATF6, which all play vital roles in returning protein homeostasis to levels seen in non-stressed cells. IRE1 is the best studied of the three pathways, as it is the only pathway present in Saccharomyces cerevisiae. This pathway involves spliceosome independent splicing of HAC1 or XBP1 in yeast and mammalians cells, respectively. PERK limits protein synthesis, therefore reducing the number of new proteins requiring folding. ATF6 is translocated and proteolytically cleaved, releasing a NH2 domain fragment which is transported to the nucleus and which affects gene expression. If the UPR is unsuccessful at reducing the load of unfolded proteins in the ER and the UPR signals remain activated, this can lead to programmed cell death.
Radial probe endobronchial ultrasound‐guided transbronchial lung biopsy for the diagnosis of cavitary peripheral pulmonary lesions

Cavitary peripheral pulmonary lesions (PPLs) are often diagnosed via transthoracic needle biopsy. However, today, radial probe endobronchial ultrasound (RP‐EBUS) is widely used to diagnose PPLs. The efficacy and safety of RP‐EBUS‐guided transbronchial lung biopsy (RP‐EBUS‐TBLB) used to diagnose cavitary PPLs remain poorly known. We investigated the utility of RP‐EBUS‐TBLB using a guide sheath (GS) without fluoroscopy to diagnose PPLs.
Learning‐dependent dendritic spine plasticity is impaired in spontaneous autoimmune encephalomyelitis

Cognitive impairment is often observed in multiple sclerosis and its animal models, experimental autoimmune encephalomyelitis (EAE). Using mice with immunization‐induced EAE, we have previously shown that the stability of cortical synapses is markedly decreased before the clinical onset of EAE. In this study, we examined learning‐dependent structural synaptic plasticity in a spontaneous EAE model. Transgenic mice expressing myelin basic protein‐specific T cell receptor genes develop EAE spontaneously at around 8 weeks of age. Using in vivo two‐photon microscopy, we found that the elimination and formation rates of postsynaptic dendritic spines in somatosensory and motor cortices increased weeks before detectable signs of EAE and remained to be high during the disease onset. Despite the elevated basal spine turnover, motor learning‐induced spine formation was reduced in presymptomatic EAE mice, in line with their impaired ability to retain learned motor skills. Additionally, we found a substantial elevation of IFN‐γ mRNA in the brain of 4‐week‐old presymptomatic mice, and treatment of anti‐IFN‐γ antibody reduced dendritic spine elimination in the cortex. Together, these findings reveal synaptic instability and failure to form new synapses after learning as early brain pathology of EAE, which may contribute to cognitive and behavioral deficits seen in autoimmune diseases.
Phenotypic recapitulation and correction of desmoglein-2-deficient cardiomyopathy using human-induced pluripotent stem cell-derived cardiomyocytes

Abstract Desmoglein-2, encoded by DSG2, is one of the desmosome proteins that maintain the structural integrity of tissues, including heart. Genetic mutations in DSG2 cause arrhythmogenic cardiomyopathy, mainly in an autosomal dominant manner. Here, we identified a homozygous stop-gain mutations in DSG2 (c.C355T, p.R119X) that led to complete desmoglein-2 deficiency in a patient with severe biventricular heart failure. Histological analysis revealed abnormal deposition of desmosome proteins, disrupted intercalated disk structures in the myocardium. Induced pluripotent stem cells (iPSCs) were generated from the patient (R119X-iPSC), and the mutated DSG2 gene locus was heterozygously corrected to a normal allele via homology-directed repair (HDR-iPSC). Both isogenic iPSCs were differentiated into cardiomyocytes [induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs)]. Multielectrode array analysis detected abnormal excitation in R119X-iPSC-CMs but not in HDR-iPSC-CMs. Micro-force testing of three-dimensional self-organized tissue rings (SOTRs) revealed tissue fragility and a weak maximum force in SOTRs from R119X-iPSC-CMs. Notably, these phenotypes were significantly recovered in HDR-iPSC-CMs. Myocardial fiber structures in R119X-iPSC-CMs were severely aberrant, and electron microscopic analysis confirmed that desmosomes were disrupted in these cells. Unexpectedly, the absence of desmoglein-2 in R119X-iPSC-CMs led to decreased expression of desmocollin-2 but no other desmosome proteins. Adeno-associated virus-mediated replacement of DSG2 significantly recovered the contraction force in SOTRs generated from R119X-iPSC-CMs. Our findings confirm the presence of a desmoglein-2-deficient cardiomyopathy among clinically diagnosed dilated cardiomyopathies. Recapitulation and correction of the disease phenotype using iPSC-CMs provide evidence to support the development of precision medicine and the proof of concept for gene replacement therapy for this cardiomyopathy.
Type I Interferon-Mediated Regulation of Antiviral Capabilities of Neutrophils

Interferons (IFNs) are induced by viruses and are the main regulators of the host antiviral response. They balance tissue tolerance and immune resistance against viral challenges. Like all cells in the human body, neutrophils possess the receptors for IFNs and contribute to antiviral host defense. To combat viruses, neutrophils utilize various mechanisms, such as viral sensing, neutrophil extracellular trap formation, and antigen presentation. These mechanisms have also been linked to tissue damage during viral infection and inflammation. In this review, we presented evidence that a complex cross-regulatory talk between IFNs and neutrophils initiates appropriate antiviral immune responses and regulates them to minimize tissue damage. We also explored recent exciting research elucidating the interactions between IFNs, neutrophils, and severe acute respiratory syndrome-coronavirus-2, as an example of neutrophil and IFN cross-regulatory talk. Dissecting the IFN-neutrophil paradigm is needed for well-balanced antiviral therapeutics and development of novel treatments against many major epidemic or pandemic viral infections, including the ongoing pandemic of the coronavirus disease that emerged in 2019.
PI(3,4)P2-mediated membrane tubulation promotes integrin trafficking and invasive cell migration

Significance The dynamic distribution of phosphoinositide lipids orchestrates intracellular compartmentalization and protein sorting. Here, we report the PI(3,4)P2-dependent endocytosis of adhesion receptor integrin-beta3 at the invadopodium and its implication in promoting invasive cell migration. PI(3,4)P2-rich compartment in the plasma membrane contains integrin-beta3 and is actively internalized through SNX9-mediated membrane invagination as well as dynein-mediated membrane tubulation along cortical microtubule tracks. Accelerated integrin endocytosis promotes adhesion turnover, and subsequent integrin exocytosis further supports cell migration. In general, the functional link between PI(3,4)P2 biogenesis and membrane internalization can be applicable to other membrane molecules at the invadopodium and provide insights into the regulation of cell migration. Invadopodia are integrin-mediated adhesions with abundant PI(3,4)P2. However, the functional role of PI(3,4)P2 in adhesion signaling remains unclear. Here, we find that the PI(3,4)P2 biogenesis regulates the integrin endocytosis at invadopodia. PI(3,4)P2 is locally produced by PIK3CA and SHIP2 and is concentrated at the trailing edge of the invadopodium arc. The PI(3,4)P2-rich compartment locally forms small puncta (membrane buds) in a SNX9-dependent manner, recruits dynein activator Hook1 through AKTIP, and rearranges into micrometer-long tubular invaginations (membrane tubes). The uncurving membrane tube extends rapidly, follows the retrograde movement of dynein along microtubule tracks, and disconnects from the plasma membrane. Activated integrin-beta3 is locally internalized through the pathway of PI(3,4)P2-mediated membrane invagination and is then actively recycled. Blockages of PI3K, SHIP2, and SNX9 suppress integrin-beta3 endocytosis, delay adhesion turnover, and impede transwell invasion of MEF-Src and MDA-MB-231 cells. Thus, the production of PI(3,4)P2 promotes invasive cell migration by stimulating the trafficking of integrin receptor at the invadopodium.
Validation of Adhesive Single-Lead ECG Device Compared with Holter Monitoring among Non-Atrial Fibrillation Patients

There are few reports on head-to-head comparisons of electrocardiogram (ECG) monitoring between adhesive single-lead and Holter devices for arrhythmias other than atrial fibrillation (AF). This study aimed to compare 24 h ECG monitoring between the two devices in patients with general arrhythmia. Twenty-nine non-AF patients with a workup of pre-diagnosed arrhythmias or suspicious arrhythmic episodes were evaluated. Each participant wore both devices simultaneously, and the cardiac rhythm was monitored for 24 h. Selective ECG parameters were compared between the two devices. Two cardiologists independently compared the diagnoses of each device. The two most frequent monitoring indications were workup of premature atrial contractions (41.4%) and suspicious arrhythmia-related symptoms (37.9%). The single-lead device had a higher noise burden than the Holter device (0.04 ± 0.05% vs. 0.01 ± 0.01%, p = 0.024). The number of total QRS complexes, ventricular ectopic beats, and supraventricular ectopic beats showed an excellent degree of agreement between the two devices (intraclass correlation coefficients = 0.991, 1.000, and 0.987, respectively). In addition, the minimum/average/maximum heart rates showed an excellent degree of agreement. The two cardiologists made coherent diagnoses for all 29 participants using both monitoring methods. In conclusion, the single-lead adhesive device could be an acceptable alternative for ambulatory ECG monitoring in patients with general arrhythmia.
The Effect of Workplace Gender Composition on Investment Interest in Hypothetical Companies

The current study extends previous work on gendered workplace attitudes by manipulating the workplace gender composition (CEO gender, employee gender) of traditional male and female employment sectors. Participants reported general financial investment interest in purported male-role congruent (science laboratory) and female-role congruent (daycare) start-up companies, where CEO gender and employee gender were orthogonally manipulated. Participants had more favorable investment attitudes toward daycares when the CEO was a woman, and especially favorable investment attitudes when both the CEO and employees were women. These findings were stronger for participants higher in hostile sexism. For science laboratories, participants reported equivalent investment attitudes, regardless of CEO gender, as long as the employee gender composition matched the CEO gender (i.e., female CEO + female employees). These findings suggest that social role expectations influence investment attitudes in predictable ways for traditional female employment sectors, but in more nuanced ways for traditional male employment sectors.
A Novel Method for COVID-19 Diagnosis Using Artificial Intelligence in Chest X-ray Images

The Coronavirus disease 2019 (COVID-19) is an infectious disease spreading rapidly and uncontrollably throughout the world. The critical challenge is the rapid detection of Coronavirus infected people. The available techniques being utilized are body-temperature measurement, along with anterior nasal swab analysis. However, taking nasal swabs and lab testing are complex, intrusive, and require many resources. Furthermore, the lack of test kits to meet the exceeding cases is also a major limitation. The current challenge is to develop some technology to non-intrusively detect the suspected Coronavirus patients through Artificial Intelligence (AI) techniques such as deep learning (DL). Another challenge to conduct the research on this area is the difficulty of obtaining the dataset due to a limited number of patients giving their consent to participate in the research study. Looking at the efficacy of AI in healthcare systems, it is a great challenge for the researchers to develop an AI algorithm that can help health professionals and government officials automatically identify and isolate people with Coronavirus symptoms. Hence, this paper proposes a novel method CoVIRNet (COVID Inception-ResNet model), which utilizes the chest X-rays to diagnose the COVID-19 patients automatically. The proposed algorithm has different inception residual blocks that cater to information by using different depths feature maps at different scales, with the various layers. The features are concatenated at each proposed classification block, using the average-pooling layer, and concatenated features are passed to the fully connected layer. The efficient proposed deep-learning blocks used different regularization techniques to minimize the overfitting due to the small COVID-19 dataset. The multiscale features are extracted at different levels of the proposed deep-learning model and then embedded into various machine-learning models to validate the combination of deep-learning and machine-learning models. The proposed CoVIR-Net model achieved 95.7% accuracy, and the CoVIR-Net feature extractor with random-forest classifier produced 97.29% accuracy, which is the highest, as compared to existing state-of-the-art deep-learning methods. The proposed model would be an automatic solution for the assessment and classification of COVID-19. We predict that the proposed method will demonstrate an outstanding performance as compared to the state-of-the-art techniques being used currently.
Isokinetic Strength and Functional Scores after Rehabilitation in Jiu-Jitsu Fighter with Repair Surgery of Pectoralis Major Muscle Rupture: A Case Report

A pectoralis major muscle rupture is a rare injury that mainly occurs during exercise. This study examined the application of rehabilitation, strength and passive range of motion (ROM) change, and subjective assessment for 1 year undertaken after repair surgery of pectoralis major muscle rupture in a Jiu-Jitsu fighter. We hypothesized that the application of ROM exercises and rehabilitation strategies contributed to muscle recovery and successful return to sports. The patient was a 34-year-old man who was injured after falling during a competitive event. The patient had pain and swelling in the front of the chest and shoulder, and the distal chest was deformed. Imaging revealed a complete rupture of the pectoralis major muscle. Reparative surgery was performed by a specialist. Immobilization was performed one week after the surgery. Passive ROM exercises began with the forward flexion 2 weeks after the surgery; abduction and external rotation ROM exercises at 4 weeks; low-intensity muscle strength exercises using tube bands at 6 weeks; machine-based pectoralis major muscle exercises at 3 months. Isokinetic equipment was used to measure horizontal adduction and internal rotation strengths, and the subjective shoulder functional and ROM scores were evaluated. Recovery of shoulder function and ROM occurred at 3 months and muscle recovery at 6 months. The participant was able to return to sports at 5 months and compete at 7 months. Although this study explored only one patient’s post-operative recovery, it suggests that ROM and strength exercises may be effective post-operative strategies for restoring function and strength to enable a return to sports.
How multisite phosphorylation impacts the conformations of intrinsically disordered proteins

Phosphorylation of intrinsically disordered proteins (IDPs) can produce changes in structural and dynamical properties and thereby mediate critical biological functions. How phosphorylation effects intrinsically disordered proteins has been studied for an increasing number of IDPs, but a systematic understanding is still lacking. Here, we compare the collapse propensity of four disordered proteins, Ash1, the C-terminal domain of RNA polymerase (CTD2’), the cytosolic domain of E-Cadherin, and a fragment of the p130Cas, in unphosphorylated and phosphorylated forms using extensive all-atom molecular dynamics (MD) simulations. We find all proteins to show V-shape changes in their collapse propensity upon multi-site phosphorylation according to their initial net charge: phosphorylation expands neutral or overall negatively charged IDPs and shrinks positively charged IDPs. However, force fields including those tailored towards and commonly used for IDPs overestimate these changes. We find quantitative agreement of MD results with SAXS and NMR data for Ash1 and CTD2’ only when attenuating protein electrostatic interactions by using a higher salt concentration (e.g. 350 mM), highlighting the overstabilization of salt bridges in current force fields. We show that phosphorylation of IDPs also has a strong impact on the solvation of the protein, a factor that in addition to the actual collapse or expansion of the IDP should be considered when analyzing SAXS data. Compared to the overall mild change in global IDP dimension, the exposure of active sites can change significantly upon phosphorylation, underlining the large susceptibility of IDP ensembles to regulation through post-translational modifications.
Spectroscopic Studies of the Roles of Distinct Chromophores in NOM Chlorination and DBP Formation

This chapter describes the results of in situ examination of chlorination in several waters (Lk. Washington, WA; Cincinnati, OH; Florence, NE; Sioux Fall, SD; Hillsborough River, FL) using the method of differential absorbance spectroscopy. The chlorination of NOM was observed to involve distinct groups of slowly and rapidly reacting chromophores. The fast chromophores in all water sources have identical spectroscopic characteristics while the properties of the slow chromophores exhibit some variability. The fast chromophores are consumed at the beginning of NOM chlorination, but their destruction is not associated with a significant release of total trihalomethanes (TTHM) or haloacetic acids (THAA). The engagement of the slow chromophores is closely associated with the generation of THMs and HAAs. Correlations between TTHM or THAA concentration and the differential absorbance associated with the slow chromophores were similar for all studied waters.