Miracle-dz/UniFAR-FTUs huggingface dataset:
Evidence for Altered Insulin Signaling in the Brains of Genetic Absence Epilepsy Rats from Strasbourg.

Insulin-mediated signaling in the brain is critical for neuronal functioning. Insulin resistance is implicated in the development of some neurological diseases, although changes associated with absence epilepsy have not been established yet. Therefore, we examined the major components of PI3K/Akt-mediated insulin signaling in cortical, thalamic, and hippocampal tissues collected from Genetic Absence Epilepsy Rats from Strasbourg (GAERS) and Non-Epileptic Control (NEC) rats. Insulin levels were also measured in plasma and cerebrospinal fluid (CSF). For the brain samples, the nuclear fraction (NF) and total homogenate (TH) were isolated and investigated for insulin signaling markers including insulin receptor beta (IRβ), IR substrate-1 and 2 (IRS1 & 2), phosphatase and tensin homolog (PTEN), phosphoinositide 3-kinase phospho-85 alpha (PI3K p85α), phosphatidylinositol 4,5-bisphosphate, phosphatidylinositol (3,4,5)-trisphosphate, protein kinase B (PKB/Akt1/2/3), glucose transporter-1 and 4 (GLUT1 & 4) and glycogen synthase kinase-3β (GSK3β) using western blotting. A significant increase in PTEN and GSK3β levels and decreased PI3K p85α and pAkt1/2/3 levels were observed in NF of GAERS cortical and hippocampal tissues. IRβ, IRS1, GLUT1, and GLUT4 levels were significantly decreased in hippocampal TH of GAERS compared to NEC. A non-significant increase in insulin levels was observed in plasma and CSF of GAERS rats. An insulin sensitivity assay showed decreased p-Akt level in cortical and hippocampal tissues. Together, altered hippocampal insulin signaling was more prominent in NF and TH compared to cortical and thalamic regions in GAERS. Restoring insulin signaling may improve the pathophysiology displayed by GAERS, including the spike-and-wave discharges that relate to absence seizures in patients.
Evidence for both sequential mutations and recombination in the evolution of kdr alleles in Aedes aegypti

Background Aedes aegypti is a globally distributed vector of human diseases including dengue, yellow fever, chikungunya, and Zika. Pyrethroid insecticides are the primary means of controlling adult A. aegypti populations to suppress arbovirus outbreaks, but resistance to pyrethroid insecticides has become a global problem. Mutations in the voltage-sensitive sodium channel (Vssc) gene are a major mechanism of pyrethroid resistance in A. aegypti. Vssc resistance alleles in A. aegypti commonly have more than one mutation. However, our understanding of the evolutionary dynamics of how alleles with multiple mutations arose is poorly understood. Methodology/Principal findings We examined the geographic distribution and association between the common Vssc mutations (V410L, S989P, V1016G/I and F1534C) in A. aegypti by analyzing the relevant Vssc fragments in 25 collections, mainly from Asia and the Americas. Our results showed all 11 Asian populations had two types of resistance alleles: 1534C and 989P+1016G. The 1534C allele was more common with frequencies ranging from 0.31 to 0.88, while the 989P+1016G frequency ranged from 0.13 to 0.50. Four distinct alleles (410L, 1534C, 410L+1534C and 410L+1016I+1534C) were detected in populations from the Americas. The most common was 410L+1016I+1534C with frequencies ranging from 0.50 to 1.00, followed by 1534C with frequencies ranging from 0.13 to 0.50. Our phylogenetic analysis of Vssc supported multiple independent origins of the F1534C mutation. Our results indicated the 410L+1534C allele may have arisen by addition of the V410L mutation to the 1534C allele, or by a crossover event. The 410L+1016I+1534C allele was the result of one or two mutational steps from a 1534C background. Conclusions/Significance Our data corroborated previous geographic distributions of resistance mutations and provided evidence for both recombination and sequential accumulation of mutations contributing to the molecular evolution of resistance alleles in A. aegypti.
Platelet-Rich Plasma Versus Hyaluronic Acid for Knee Osteoarthritis: A Systematic Review and Meta-analysis of Randomized Controlled Trials

Background: Platelet-rich plasma (PRP) and hyaluronic acid (HA) are 2 nonoperative treatment options for knee osteoarthritis (OA) that are supposed to provide symptomatic relief and help delay surgical intervention. Purpose: To systematically review the literature to compare the efficacy and safety of PRP and HA injections for the treatment of knee OA. Study Design: Meta-analysis of level 1 studies. Methods: A systematic review was performed by searching PubMed, the Cochrane Library, and Embase to identify level 1 studies that compared the clinical efficacy of PRP and HA injections for knee OA. The search phrase used was platelet-rich plasma hyaluronic acid knee osteoarthritis randomized. Patients were assessed via the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), visual analog scale (VAS) for pain, and Subjective International Knee Documentation Committee (IKDC) scale. A subanalysis was also performed to isolate results from patients who received leukocyte-poor and leukocyte-rich PRP. Results: A total of 18 studies (all level 1) met inclusion criteria, including 811 patients undergoing intra-articular injection with PRP (mean age, 57.6 years) and 797 patients with HA (mean age, 59.3 years). The mean follow-up was 11.1 months for both groups. Mean improvement was significantly higher in the PRP group (44.7%) than the HA group (12.6%) for WOMAC total scores (P < .01). Of 11 studies based on the VAS, 6 reported PRP patients to have significantly less pain at latest follow-up when compared with HA patients (P < .05). Of 6 studies based on the Subjective IKDC outcome score, 3 reported PRP patients to have significantly better scores at latest follow-up when compared with HA patients (P < .05). Finally, leukocyte-poor PRP was associated with significantly better Subjective IKDC scores versus leukocyte-rich PRP (P < .05). Conclusion: Patients undergoing treatment for knee OA with PRP can be expected to experience improved clinical outcomes when compared with HA. Additionally, leukocyte-poor PRP may be a superior line of treatment for knee OA over leukocyte-rich PRP, although further studies are needed that directly compare leukocyte content in PRP injections for treatment of knee OA.
A study on faciomaxillary trauma in a tertiary care hospital: a prospective study

Background: Faciomaxillary injuries are increasing in incidence in Tirunelveli district due to the increasing number of vehicles on the street which are inadequate and due to assault. The common denominator in both these situations is alcohol abuse. This study aims to assess the incidence, causative factors and management options of Faciomaxillary trauma.Methods: Around 50 case of faciomaxillary injuries admitted in the Department of Plastic surgery, TVMCH were taken up for study. The cases were studied for age, sex, personal habits, mode of injury, associated injuries, involved bones and type of fracture, clinical features, treatment modalities, and complications.Results: Road Traffic Accident (RTA) was the most common cause. Males aged 20-30 were the most commonly involved. Alcohol abuse and Intoxication was the most common antecedent event. Associated head, limbs and chest injuries were common. Mandible was the commonest bone to be fractured followed by zygoma, maxilla and nasal bones. ORIF and IMF was the common surgery performed.Conclusions: Alcohol abuse is the leading cause of faciomaxillary injuries. Educating the public about the traffic rules and the ill effects of drunken driving will go a long way to prevent these injuries.
Comparative pathogenesis of COVID-19, MERS, and SARS in a nonhuman primate model

Coronavirus in nonhuman primates We urgently need vaccines and drug treatments for coronavirus disease 2019 (COVID-19). Even under these extreme circumstances, we must have animal models for rigorous testing of new strategies. Rockx et al. have undertaken a comparative study of three human coronaviruses in cynomolgus macaques: severe acute respiratory syndrome–coronavirus (SARS-CoV) (2002), Middle East respiratory syndrome (MERS)–CoV (2012), and SARS-CoV-2 (2019), which causes COVID-19 (see the Perspective by Lakdawala and Menachery). The most recent coronavirus has a distinct tropism for the nasal mucosa but is also found in the intestinal tract. Although none of the older macaques showed the severe symptoms that humans do, the lung pathology observed was similar. Like humans, the animals shed virus for prolonged periods from their upper respiratory tracts, and like influenza but unlike the 2002 SARS-CoV, this shedding peaked early in infection. It is this cryptic virus shedding that makes case detection difficult and can jeopardize the effectiveness of isolation. Science, this issue p. 1012; see also p. 942 SARS-CoV-2 infection in macaques results in COVID-19–like disease with prolonged virus shedding from the nose and throat in the absence of symptoms. The current pandemic coronavirus, severe acute respiratory syndrome–coronavirus 2 (SARS-CoV-2), was recently identified in patients with an acute respiratory syndrome, coronavirus disease 2019 (COVID-19). To compare its pathogenesis with that of previously emerging coronaviruses, we inoculated cynomolgus macaques with SARS-CoV-2 or Middle East respiratory syndrome (MERS)–CoV and compared the pathology and virology with historical reports of SARS-CoV infections. In SARS-CoV-2–infected macaques, virus was excreted from nose and throat in the absence of clinical signs and detected in type I and II pneumocytes in foci of diffuse alveolar damage and in ciliated epithelial cells of nasal, bronchial, and bronchiolar mucosae. In SARS-CoV infection, lung lesions were typically more severe, whereas they were milder in MERS-CoV infection, where virus was detected mainly in type II pneumocytes. These data show that SARS-CoV-2 causes COVID-19–like disease in macaques and provides a new model to test preventive and therapeutic strategies.
Bilirubin levels in patients with mild and severe Covid‐19: A pooled analysis

The letter comments on a recent commentary published in Liver International entitled "COVID-19 and liver disease" by Sun et al., and describes a pooled analysis of data on bilirubin levels in patients with and without severe Covid-19. This is the first pooled analysis of data on bilirubin in Covid-19 patients. The results evidence that bilirubin levels are significantly associated with the severity of the disease.
Impact of law enforcement and increased traffic fines policy on road traffic fatality, injuries and offenses in Iran: Interrupted time series analysis

Background Road traffic law enforcement was implemented on 1st April 2011 (the first intervention) and traffic ticket fines have been increased on 1st March 2016 (the second intervention) in Iran. The aim of the current study was to evaluate the effects of the law enforcement on reduction in the incidence rate of road traffic fatality (IRRTF), the incidence rate of road traffic injuries (IRRTI) and the incidence rate of rural road traffic offenses (IRRRTO) in Iran. Methods Interrupted time series analysis was conducted to evaluate the impact of law enforcement and increased traffic tickets fines. Monthly data of fatality on urban, rural and local rural roads, injuries with respect to gender and traffic offenses namely speeding, illegal overtaking and tailgating were investigated separately for the period 2009–2016. Results Results showed a reduction in the incidence rate of total road traffic fatality (IRTRTF), the incidence rate of rural road traffic fatality (IRRRTF) and the incidence rate of urban road traffic fatality (IRURTF) by –21.44% (–39.3 to –3.59, 95% CI), –21.25% (–31.32 to –11.88, 95% CI) and –26.75% (–37.49 to –16, 95% CI) through the first intervention which resulted in 0.383, 0.255 and 0.222 decline in casualties per 100 000 population, respectively. Conversely, no reduction was found in the incidence rate of local rural road traffic fatality (IRLRRTF) and the IRRTI. Second intervention was found to only affect the IRURTF with –26.75% (–37.49 to –16, 95% CI) which led to 0.222 casualties per 100 000 population. In addition, a reduction effect was observed on the incidence rate of illegal overtaking (IRIO) and the incidence rate of speeding (IRS) with –42.8% (–57.39 to –28.22, 95% CI) and –10.54% (–21.05 to –0.03, 95% CI which implied a decrease of 415.85 and 1003.8 in monthly traffic offenses per 100 000 vehicles), respectively. Conclusion Time series analysis suggests a decline in IRTRTF, IRRRTF, and IRURTF caused by the first intervention. However, the second intervention found to be only effective in IRURTF, IRIO, and IRS with the implication that future initiatives should be focused on modifying the implementation of the traffic interventions.
Medical Assistance in Dying: Patients', Families', and Health Care Providers' Perspectives on Access and Care Delivery.

Background: Medical assistance in dying (MAID) became legal in Canada in 2016. Although the legislation is federal, each province is responsible for establishing quality care. Objective: To explore patient, family, and health care provider (HCP) perspectives on MAID access and care delivery and improve regional MAID care delivery. Design: Qualitative exploratory. Setting/Subjects: We interviewed 5 patients (4 met the legislated MAID criteria and 1 did not), 11 family members (4 spouses, 5 children, 1 sibling, and 1 friend), and 14 HCP (3 physicians, 4 social workers, and 7 nurses) from June to August 2017. Measurement: Semistructured interviews, content analysis, and thematic summary. Results: Patients, families, and HCPs highlighted access and delivery concerns regarding program sustainability, care pathway ambiguity, lack of support for care choices, institutional conscientious objection (CO), navigating care in institutions with a CO, and postdeath documentation. Patients and families expressed additional concerns regarding lack of ability to provide advanced MAID consent, and the requirement of independent witnesses on MAID request forms and consent immediately before MAID administration. HCPs were additionally uncertain about professional roles and responsibilities. Ten recommendations to improve regional MAID care and the resultant practice change are presented. Conclusion: Quality improvement (QI) processes are essential to devise an accessible dignified patient- and family-centered MAID program. Ensuring patient and family perspectives are integrated into QI initiatives will assist programs in ensuring the needs of all are considered in structuring and staffing a program that is accessible, easy to navigate, and provides dignified end-of-life care in supportive and respectful work environments.
A comprehensive study of phospholipid fatty acid rearrangements in metabolic syndrome: correlations with organ dysfunction

ABSTRACT The balance within phospholipids (PLs) between saturated fatty acids and monounsaturated or polyunsaturated fatty acids is known to regulate the biophysical properties of cellular membranes. As a consequence, in many cell types, perturbing this balance alters crucial cellular processes, such as vesicular budding and the trafficking/function of membrane-anchored proteins. The worldwide spread of the Western diet, which is highly enriched in saturated fats, has been clearly correlated with the emergence of a complex syndrome known as metabolic syndrome (MetS). MetS is defined as a cluster of risk factors for cardiovascular diseases, type 2 diabetes and hepatic steatosis; however, no clear correlations have been established between diet-induced fatty acid redistribution within cellular PLs and the severity/chronology of the symptoms associated with MetS or the function of the targeted organs. To address this issue, in this study we analyzed PL remodeling in rats exposed to a high-fat/high-fructose diet (HFHF) over a 15-week period. PL remodeling was analyzed in several organs, including known MetS targets. We show that fatty acids from the diet can redistribute within PLs in a very selective manner, with phosphatidylcholine being the preferred sink for this redistribution. Moreover, in the HFHF rat model, most organs are protected from this redistribution, at least during the early onset of MetS, at the expense of the liver and skeletal muscles. Interestingly, such a redistribution correlates with clear-cut alterations in the function of these organs. This article has an associated First Person interview with the first author of the paper. Summary: In rats, a high-fat diet induces the selective distribution of fatty acids within phosphatidylcholine in the liver and muscles, in a manner that correlates with organ dysfunction. The cardiovascular system appears to be protected under these conditions.
Deep learning with diffusion basis spectrum imaging for classification of multiple sclerosis lesions

Multiple sclerosis (MS) lesions are heterogeneous with regard to inflammation, demyelination, axonal injury, and neuronal loss. We previously developed a diffusion basis spectrum imaging (DBSI) technique to better address MS lesion heterogeneity. We hypothesized that the profiles of multiple DBSI metrics can identify lesion‐defining patterns. Here we test this hypothesis by combining a deep learning algorithm using deep neural network (DNN) with DBSI and other imaging methods.
Two‐year drug survival of dupilumab in a large cohort of difficult‐to‐treat adult atopic dermatitis patients compared to cyclosporine A and methotrexate: Results from the BioDay registry

3 Department of Internal Medicine , Kyung Hee University Medical Center , Seoul , Korea 4 Department of Pathology , Seoul National University College of Medicine , Seoul , Korea 5 Laboratory of Immune Regulation , Department of Biomedical Sciences , Seoul National University College of Medicine , Seoul , Korea 6 Institute of Allergy and Clinical Immunology , Seoul National University Medical Research Center , Seoul , Korea
Influence of the tubular network on the characteristics of calcium transients in cardiac myocytes

Transverse and axial tubules (TATS) are an essential ingredient of the excitation-contraction machinery that allow the effective coupling of L-type Calcium Channels (LCC) and ryanodine receptors (RyR2). They form a regular network in ventricular cells, while their presence in atrial myocytes is variable regionally and among animal species We have studied the effect of variations in the TAT network using a bidomain computational model of an atrial myocyte with variable density of tubules. At each z-line the t-tubule length is obtained from an exponential distribution, with a given mean penetration length. This gives rise to a distribution of t-tubules in the cell that is characterized by the fractional area (F.A.) occupied by the t-tubules. To obtain consistent results, we average over different realizations of the same mean penetration length. To this, in some simulations we add the effect of a network of axial tubules. Then we study global properties of calcium signaling, as well as regional heterogeneities and local properties of sparks and RyR2 openings. In agreement with recent experiments in detubulated ventricular and atrial cells, we find that detubulation reduces the calcium transient and synchronization in release. However, it does not affect sarcoplasmic reticulum (SR) load, so the decrease in SR calcium release is due to regional differences in Ca2+ release, that is restricted to the cell periphery in detubulated cells. Despite the decrease in release, the release gain is larger in detubulated cells, due to recruitment of orphaned RyR2s, i.e, those that are not confronting a cluster of LCCs. This probably provides a safeguard mechanism, allowing physiological values to be maintained upon small changes in the t-tubule density. Finally, we do not find any relevant change in spark properties between tubulated and detubulated cells, suggesting that the differences found in experiments could be due to differential properties of the RyR2s in the membrane and in the t-tubules, not incorporated in the present model. This work will help understand the effect of detubulation, that has been shown to occur in disease conditions such as heart failure (HF) in ventricular cells, or atrial fibrillation (AF) in atrial cells.
Monte Carlo track-structure for the radionuclide Copper-64: characterization of S-values, nanodosimetry and quantification of direct damage to DNA

TOPAS-nBio was used to simulate, collision-to-collision, the complete trajectories of electrons in water generated during the explicit simulation of 64Cu decay. S-values and direct damage to the DNA were calculated representing the cell (C) and the cell nucleus (N) with concentric spheres of 5 μm and 4 μm in radius, respectively. The considered ‘target’←‘source’ configurations, including the cell surface (Cs) and cytoplasm (Cy), were: C←C, C←Cs, N←N, N←Cy and N←Cs. Ionization cluster size distributions were also calculated in a cylinder immersed in water corresponding to a DNA segment of 10 base-pairs in length (diameter 2.3 nm, length 3.4 nm), modeling a radioactive point source moving from the central axis to the edge of the cylinder. For that, the first moment (M1) and cumulative probability of having a cluster size of 2 or more ionizations in the cylindrical volume (F2) were obtained. Finally, the direct damage to the DNA was estimated by quantifying double-strand breaks (DSBs) using the clustering algorithm DBSCAN. The S-values obtained with TOPAS-nBio for 64Cu were 7.879 × 10−4 ± 5 × 10−7, 4.351 × 10−4 ± 6 × 10−7, 1.442 × 10−3 ± 1 × 10−6, 2.596 × 10−4 ± 8 × 10−7, 1.127 × 10−4 ± 4 × 10−7 Gy Bq-s−1 for the configurations C←C, C←Cs, N←N, N←Cy and N←Cs, respectively. The difference of these values, compared with previously reported S-values for 64Cu with the code MNCP and software MIRDCell, ranged from −4% to −25% for the configurations N←N and N←Cs, respectively. On the other hand, F2 was maximum with the source at the center of the cylinder 0.373 ± 0.001, and monotonically decreased until reaching a value of 0.058 ± 0.001 at 2.3 nm. The same behavior was observed for M1 with values ranging from 2.188 ± 0.004 to 0.242 ± 0.002. Finally, the DBSCAN algorithm showed that the mean number of DNA DSBs per decay were 0.187 ± 0.001, 0.0317 ± 0.0005, and 0.0125 ± 0.0002 DSB-(Bq-s)−1 for the configurations N←N, N←Cs, and N←Cy, respectively. In conclusion, the results of the S-values show that the absorbed dose strongly depends on the distribution of the radionuclide in the cell, the dose being higher when 64Cu is internalized in the cell nucleus, which is reinforced by the nanodosimetric study by the presence of DNA DSBs attributable to the Auger electrons emitted during the decay of 64Cu.