Miracle-dz/UniFAR-FTUs huggingface dataset:
On the construction and decoding of concatenated polar codes

A scheme for concatenating the recently invented polar codes with interleaved block codes is considered. By concatenating binary polar codes with interleaved Reed-Solomon codes, we prove that the proposed concatenation scheme captures the capacity-achieving property of polar codes, while having a significantly better error-decay rate. We show that for any ε > 0, and total frame length N, the parameters of the scheme can be set such that the frame error probability is less than 2-N 1-ε, while the scheme is still capacity achieving. This improves upon 2-N 0.5-ε, the frame error probability of Arikan's polar codes. We also propose decoding algorithms for concatenated polar codes, which significantly improve the error-rate performance at finite block lengths while preserving the low decoding complexity.
Inhibition of Newcastle Disease Virus Replication by Lentivirus-Mediated RNA Interference

SUMMARY Small interfering RNA (siRNA)-induced RNA degradation can specifically inhibit viral infection and has been extensively investigated for its efficacy as an antiviral therapeutic approach. In this study we constructed a lentivirus vector carrying a U6-short hairpin RNA expression cassette to express siRNAs in vero cells. The lentivirus vector also expressed an enhanced green fluorescence protein as a reporter. Stable siRNA-expressing cell lines were successfully established, and the inhibition efficiencies of rationally designed siRNAs targeting conserved genomic regions of the Newcastle disease virus, an important disease of poultry world wide, were assessed. Our results showed that siRNAs targeting the nucleoprotein and matrix gene potently inhibited viral replication. Our study indicates that lentivirus-mediated delivery of siRNA and the resulting gene silencing can be used to study the functions of genes in viral replication and may have a potential transgenic antiviral application in poultry. RESUMEN Inhibición de la replicación del virus de la enfermedad de Newcastle por interferencia mediada ARN de lentivirus. La degradación específica de ARN inducida por moléculas de ARN pequeñas de interferencia (siRNA) pueden inhibir la infección viral y se han investigado extensamente por su eficacia como un enfoque terapéutico antiviral. En este estudio se construyó un vector de lentivirus que contiene un casete de expresión de ARN U6 en forma de horquilla para expresar siRNAs en células Vero. El vector de lentivirus también expresaba una proteína verde fluorescente y aumentada como reportera. Se establecieron con éxito líneas celulares que expresaban de manera estable siRNA, y se evaluaron las eficiencias de inhibición de siRNAs diseñados racionalmente que estaban dirigidos a regiones genómicas conservadas del virus de la enfermedad de Newcastle, que es una enfermedad importante en avicultura a nivel mundial. Nuestros resultados mostraron que los siRNAs dirigidos a los genes de la nucleoproteína y de la matriz inhiben potentemente la replicación viral. Este estudio indica que la administración de siRNA mediada por lentivirus y el silenciamiento de genes resultante, se pueden utilizar para estudiar las funciones de los genes en la replicación viral y puede tener un potencial de aplicación transgénica antiviral en la avicultura.
Transcriptome Sequencing of Immature Ants Reveals the Complete Genome Sequence of a New Isolate of Solenopsis invicta Virus 2 from the Mississippi Delta

Solenopsis invicta virus 2 (SINV-2) is an RNA virus that infects red imported fire ants. I report the genome sequence of SINV-2MSD, an isolate infecting ants collected from Mississippi. ABSTRACT Solenopsis invicta virus 2 (SINV-2) is an RNA virus that infects red imported fire ants. I report the genome sequence of SINV-2MSD, an isolate infecting ants collected from Mississippi. The obtained genome is 11,303 nucleotides, including six open reading frames encoding four structural proteins, a helicase, and an RNA-dependent RNA polymerase.
Electroconvulsive Shock Enhances Responsive Motility and Purinergic Currents in Microglia in the Mouse Hippocampus

Abstract Microglia are in a privileged position to both affect and be affected by neuroinflammation, neuronal activity and injury, which are all hallmarks of seizures and the epilepsies. Hippocampal microglia become activated after prolonged, damaging seizures known as status epilepticus (SE). However, since SE causes both hyperactivity and injury of neurons, the mechanisms triggering this activation remain unclear, as does the relevance of the microglial activation to the ensuing epileptogenic processes. In this study, we use electroconvulsive shock (ECS) to study the effect of neuronal hyperactivity without neuronal degeneration on mouse hippocampal microglia. Unlike SE, ECS did not alter hippocampal CA1 microglial density, morphology, or baseline motility. In contrast, both ECS and SE produced a similar increase in ATP-directed microglial process motility in acute slices, and similarly upregulated expression of the chemokine C-C motif chemokine ligand 2 (CCL2). Whole-cell patch-clamp recordings of hippocampal CA1sr microglia showed that ECS enhanced purinergic currents mediated by P2X7 receptors in the absence of changes in passive properties or voltage-gated currents, or changes in receptor expression. This differs from previously described alterations in intrinsic characteristics which coincided with enhanced purinergic currents following SE. These ECS-induced effects point to a “seizure signature” in hippocampal microglia characterized by altered purinergic signaling. These data demonstrate that ictal activity per se can drive alterations in microglial physiology without neuronal injury. These physiological changes, which up until now have been associated with prolonged and damaging seizures, are of added interest as they may be relevant to electroconvulsive therapy (ECT), which remains a gold-standard treatment for depression.
Dendritic Cell Vaccination in Glioblastoma Patients Induces Systemic and Intracranial T-cell Responses Modulated by the Local Central Nervous System Tumor Microenvironment

Purpose: We previously reported that autologous dendritic cells pulsed with acid-eluted tumor peptides can stimulate T cell–mediated antitumor immune responses against brain tumors in animal models. As a next step in vaccine development, a phase I clinical trial was established to evaluate this strategy for its feasibility, safety, and induction of systemic and intracranial T-cell responses in patients with glioblastoma multiforme. Experimental Design: Twelve patients were enrolled into a multicohort dose-escalation study and treated with 1, 5, or 10 million autologous dendritic cells pulsed with constant amounts (100 μg per injection) of acid-eluted autologous tumor peptides. All patients had histologically proven glioblastoma multiforme. Three biweekly intradermal vaccinations were given; and patients were monitored for adverse events, survival, and immune responses. The follow-up period for this trial was almost 5 years. Results: Dendritic cell vaccinations were not associated with any evidence of dose-limiting toxicity or serious adverse effects. One patient had an objective clinical response documented by magnetic resonance imaging. Six patients developed measurable systemic antitumor CTL responses. However, the induction of systemic effector cells did not necessarily translate into objective clinical responses or increased survival, particularly for patients with actively progressing tumors and/or those with tumors expressing high levels of transforming growth factor β2 (TGF-β2). Increased intratumoral infiltration by cytotoxic T cells was detected in four of eight patients who underwent reoperation after vaccination. The magnitude of the T-cell infiltration was inversely correlated with TGF-β2 expression within the tumors and positively correlated with clinical survival (P = 0.047). Conclusions: Together, our results suggest that the absence of bulky, actively progressing tumor, coupled with low TGF-β2 expression, may identify a subgroup of glioma patients to target as potential responders in future clinical investigations of dendritic cell–based vaccines.
MyDGR: a server for identification and characterization of diversity-generating retroelements

Abstract MyDGR is a web server providing integrated prediction and visualization of Diversity-Generating Retroelements (DGR) systems in query nucleotide sequences. It is built upon an enhanced version of DGRscan, a tool we previously developed for identification of DGR systems. DGR systems are remarkable genetic elements that use error-prone reverse transcriptases to generate vast sequence variants in specific target genes, which have been shown to benefit their hosts (bacteria, archaea or phages). As the first web server for annotation of DGR systems, myDGR is freely available on the web at http://omics.informatics. indiana.edu/myDGR with all major browsers supported. MyDGR accepts query nucleotide sequences in FASTA format, and outputs all the important features of a predicted DGR system, including a reverse transcriptase, a template repeat and one (or more) variable repeats and their alignment featuring A-to-N (N can be C, T or G) substitutions, and VR-containing target gene(s). In addition to providing the results as text files for download, myDGR generates a visual summary of the results for users to explore the predicted DGR systems. Users can also directly access pre-calculated, putative DGR systems identified in currently available reference bacterial genomes and a few other collections of sequences (including human microbiomes).
Extensive distribution of glial cytoplasmic inclusions in an autopsied case of multiple system atrophy with a prolonged 18‐year clinical course

We describe herein an autopsied case of multiple system atrophy (MSA) with prolonged clinical course of 18 years, and evaluate the extent of neurodegeneration and glial cytoplasmic inclusions (GCIs) in the entire brain of this rare case. A 64‐year‐old woman presented with typical neurological symptoms and imaging features of MSA. Thereafter, she became bedridden, and breathing was assisted through a tracheostomy for 12 years. She died at the age of 82 after 18 years from the initial symptom. Post mortem examination revealed severe neurodegeneration in the inferior olive, pontine nuclei, substantia nigra, locus ceruleus, putamen and cerebellum. Notably, phosphorylated α‐synuclein (p‐α‐syn)‐positive GCIs were found in these areas, but their number was very low. In contrast, the density of GCIs was much higher in such regions as the tectum/tegmentum of the brainstem, pyramidal tracts, neocortices and limbic system, which usually contain a small number of GCIs. Another constituent of GCIs, ubiquitin (Ub) and Ub‐associated autophagy substrate p62, were also positive in some GCIs, and distribution of Ub/p62 immunoreactivity was proportionate to that of p‐α‐syn+ GCIs despite the very long duration of the disease. Furthermore, this case had complicated hypoxic encephalopathy, but p‐α‐syn+ GCIs were also found in the damaged white matter, indicating the contribution of α‐syncleinopathy as well as hypoxic effect to the secondary myelin and axonal loss in the white matter. Together, this rare case suggests the contribution of the disease duration to the prevalence of GCIs, and the possible involvement of the limbic system in extensive‐stage disease.
Chinese herbal medicine for diabetic kidney disease: a systematic review and meta-analysis of randomised placebo-controlled trials

Objectives To provide a broad evaluation of the efficacy and safety of oral Chinese herbal medicine (CHM) as an adjunctive treatment for diabetic kidney disease (DKD), including mortality, progression to end-stage kidney disease (ESKD), albuminuria, proteinuria and kidney function. Design A systematic review and meta-analysis. Methods Randomised controlled trials (RCTs) comparing oral CHM with placebo as an additional intervention to conventional treatments were retrieved from five English (Cochrane Central Register of Controlled Trials, MEDLINE, Embase, Allied and Complementary Medicine Database and Cumulative Index of Nursing and Allied Health Literature) and four Chinese databases (China BioMedical Literature, China National Knowledge Infrastructure, Chonqing VIP and Wanfang) from inception to May 2018. RCTs recruiting adult DKD patients induced by primary diabetes were considered eligible, regardless of the form and ingredients of oral CHM. Mean difference (MD) or standardised mean difference (SMD) was used to analyse continuous variables and RR for dichotomous data. Results From 7255 reports retrieved, 20 eligible studies involving 2719 DKD patients were included. CHM was associated with greater reduction of albuminuria than placebo, regardless of whether renin–angiotensin system (RAS) inhibitors were concurrently administered (SMD −0.56, 95% CI [−1.04 to –0.08], I2=64%, p=0.002) or not (SMD −0.92, 95% CI [−1.35 to –0.51], I2=87%, p<0.0001). When CHM was used as an adjunct to RAS inhibitors, estimated glomerular filtration rate was higher in the CHM than placebo group (MD 6.28 mL/min; 95% CI [2.42 to 10.14], I2=0%, p=0.001). The effects of CHM on progression to ESKD and mortality were uncertain due to low event rates. The reported adverse events in CHM group included digestive disorders, elevated liver enzyme level, infection, anaemia, hypertension and subarachnoid haemorrhage, but the report rates were low and similar to control groups. The favourable results of CHM should be balanced with the limitations of the included studies such as high heterogeneity, short follow-up periods, small numbers of clinical events and older patients with less advanced disease. Conclusions Based on moderate to low quality evidence, CHM may have beneficial effects on renal function and albuminuria beyond that afforded by conventional treatment in adults with DKD. Further well-conducted, adequately powered trials with representative DKD populations are warranted to confirm the long-term effect of CHM, particularly on clinically relevant outcomes. PROSPERO registration number CRD42015029293.
Baseline characteristics of depressive disorders in Thai outpatients: findings from the Thai Study of Affective Disorders

Background The Thai Study of Affective Disorders was a tertiary hospital-based cohort study developed to identify treatment outcomes among depressed patients and the variables involved. In this study, we examined the baseline characteristics of these depressed patients. Methods Patients were investigated at eleven psychiatric outpatient clinics at tertiary hospitals for the presence of unipolar depressive disorders, as diagnosed by the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. The severity of any depression found was measured using the Clinical Global Impression and 17-item Hamilton Depression Rating Scale (HAMD) clinician-rated tools, with the Thai Depression Inventory (a self-rated instrument) administered alongside them. Sociodemographic and psychosocial variables were collected, and quality of life was also captured using the health-related quality of life (SF-36v2), EuroQoL (EQ-5D), and visual analog scale (EQ VAS) tools. Results A total of 371 outpatients suffering new or recurrent episodes were recruited. The mean age of the group was 45.7±15.9 (range 18–83) years, and 75% of the group was female. In terms of diagnosis, 88% had major depressive disorder, 12% had dysthymic disorder, and 50% had a combination of both major depressive disorder and dysthymic disorder. The mean (standard deviation) scores for the HAMD, Clinical Global Impression, and Thai Depression Inventory were 24.2±6.4, 4.47±1.1, and 51.51±0.2, respectively. Sixty-two percent had suicidal tendencies, while 11% had a family history of depression. Of the major depressive disorder cases, 61% had experienced a first episode. The SF-36v2 component scores ranged from 25 to 56, while the mean (standard deviation) of the EQ-5D was 0.50±0.22 and that of the EQ VAS was 53.79±21.3. Conclusion This study provides an overview of the sociodemographic and psychosocial characteristics of patients with new or recurrent episodes of unipolar depressive disorders.
Adherence and Attrition in a Web-Based Lifestyle Intervention for People with Metabolic Syndrome

Abstract Background The aim of this study was to determine adherence and attrition rates in a lifestyle intervention for people with metabolic syndrome. Methods Adherence and attrition data from a randomized controlled trial were collected. Participants were classified as adherence group if they completed assessments at 3 and 6 months follow-up and as attrition group if they did not. Physical activity and quality of life was measured using the International Physical Activity Questionnaire (IPAQ) and the Short Form Health Survey (SF-36). Generalized Estimating Equations (GEE) was used to explore predictors of attrition. Results The mean age of participants (n=160) was 44.1 years. Attrition rate in the intervention and control groups at first follow-up were the same (20%). However, the control group had significantly higher attrition rate (%33.7) compared to the intervention group (%20) at 6 months follow up. Results showed that low educated participants were more likely to not stay in the study than better educated participants (OR=2.95,CI:1.39-6.33,P=0.05). According with length of the study, attrition was decreased at six month (OR=0.66,CI:0.52-0.83,P<0.001). Also, some aspects of health-related quality of life contributed to the attrition rate. Those who had higher scores on general health (OR=0.66,CI:0.54-0.97,P=0.023), social functioning (OR=0.44,CI:0.40-0.76,P=0.032), role emotional (OR=0.74,CI:0.54-0.98,P=0.18), vitality (OR=0.55,CI:0.38-0.90,P=0.015) and mental health (OR=0.63,CI:0.45-0.85,P=0.033) were more likely to stay in the study. Conclusion It remains a concern that Web-based lifestyle programs may fail to reach those who need it most. Participant in the study generally had better quality of life than those who were lost to follow up.
Tertiary butylhydroquinone alleviates gestational diabetes mellitus in C57BL/KsJ‐Lep db/+ mice by suppression of oxidative stress

Gestational diabetes mellitus (GDM) is a common disorder characterized by abnormal glucose metabolism during pregnancy, affecting 2% to 5% of pregnant women. Currently, clinical treatment for GDM is very limited. The present study was designed to investigate the effect and underlying molecular mechanism of tertiary butylhydroquinone (TBHQ) in a pregnant C57BL/KsJ‐Lep db/+ (referred to as db+) GDM mouse model. The results showed that nonpregnant db/+ mice did not show a diabetic phenotype, and TBHQ had no effect on glucose and insulin tolerance in these mice. Moreover, in db/+ pregnant mice exhibiting typical diabetes symptoms, such as hyperglycemia and hypoinsulinemia, TBHQ could remarkably decrease the blood glucose level, increase insulin level, and improve glucose and insulin intolerance. The results also revealed that TBHQ could inhibit oxidative stress in pregnant db/+ mice. Furthermore, TBHQ greatly improved offspring survival rate, glucose metabolism, and insulin tolerance. In addition, TBHQ inhibited oxidative stress by reducing malondialdehyde (MDA) and reactive oxygen species (ROS) levels and increased superoxide dismutase (SOD), and glutathione peroxidase (GPx) activities. Moreover, we found that TBHQ activated the nuclear factor erythroid 2‐related factor 2 (Nrf2), thereby increasing the levels of Nrf2, and ultimately upregulating the expression of heme oxygenase 1 (NO‐1) and superoxide dismutase 2 (SOD2). In conclusion, our findings demonstrated that TBHQ alleviated GDM via Nrf2 activation.
Breadth of neutralization and synergy of clinically relevant human monoclonal antibodies against HCV genotypes 1a, 1b, 2a, 2b, 2c, and 3a

Human monoclonal antibodies (HMAbs) with neutralizing capabilities constitute potential immune‐based treatments or prophylaxis against hepatitis C virus (HCV). However, lack of cell culture‐derived HCV (HCVcc) harboring authentic envelope proteins (E1/E2) has hindered neutralization investigations across genotypes, subtypes, and isolates. We investigated the breadth of neutralization of 10 HMAbs with therapeutic potential against a panel of 16 JFH1‐based HCVcc‐expressing patient‐derived Core‐NS2 from genotypes 1a (strains H77, TN, and DH6), 1b (J4, DH1, and DH5), 2a (J6, JFH1, and T9), 2b (J8, DH8, and DH10), 2c (S83), and 3a (S52, DBN, and DH11). Virus stocks used for in vitro neutralization analysis contained authentic E1/E2, with the exception of full‐length JFH1 that acquired the N417S substitution in E2. The 50% inhibition concentration (IC50) for each HMAb against the HCVcc panel was determined by dose‐response neutralization assays in Huh7.5 cells with antibody concentrations ranging from 0.0012 to 100 μg/mL. Interestingly, IC50 values against the different HCVcc's exhibited large variations among the HMAbs, and only three HMAbs (HC‐1AM, HC84.24, and AR4A) neutralized all 16 HCVcc recombinants. Furthermore, the IC50 values for a given HMAb varied greatly with the HCVcc strain, which supports the use of a diverse virus panel. In cooperation analyses, HMAbs HC84.24, AR3A, and, especially HC84.26, demonstrated synergistic effects towards the majority of the HCVcc's when combined individually with AR4A. Conclusion: Through a neutralization analysis of 10 clinically relevant HMAbs against 16 JFH1‐based Core‐NS2 recombinants from genotypes 1a, 1b, 2a, 2b, 2c, and 3a, we identified at least three HMAbs with potent and broad neutralization potential. The neutralization synergism obtained when pooling the most potent HMAbs could have significant implications for developing novel strategies to treat and control HCV. (Hepatology 2014;60:1551–1562)
Prevalence and relationship between burnout and depression in our future doctors: a cross-sectional study in a cohort of preclinical and clinical medical students in Ireland

Objectives This cross-sectional study was designed to measure burnout and its impact on risk of depression in a medical student population, comparing the preclinical and clinical years. Design We conducted a survey of 269 medical school students in both preclinical and clinical years at the Royal College of Surgeons in Ireland, using the Beck Depression Inventory-Fast Screen (BDI-FS), the Maslach Burnout Inventory-Student Survey and items assessing willingness to use mental health services. Burnout scores were calibrated to probability of depression caseness and classified as low risk (<25%), intermediate (25%–50%) and high risk (>50%) of depression. Results There was a 39% (95% CI 33% to 45%) prevalence of depressive caseness based on a score of ≥6 on the BDI-FS. Prevalence did not vary significantly between clinical and preclinical years. The rate of burnout varied significantly between years (p=0.032), with 35% in the high-burnout category in clinical years compared with 26% in preclinical years. Those in the low burnout category had a 13% overall prevalence of depressive symptoms, those in the intermediate category had a 38% prevalence and those in the high category had a 66% prevalence of depressive symptoms. Increasing emotional exhaustion (OR for one—tertile increase in score 2.0, p=0.011) and decreasing academic efficacy (OR 2.1, p=0.007) increased the odds of being unwilling to seek help for mental health problems (11%). Conclusion While previous studies have reported significant levels of burnout and depression, our method of calibrating burnout against depression allows burnout scores to be interpreted in terms of their impact on mental health. The high prevalences, in line with previous research, point to an urgent need to rethink the psychological pressures of health professions education.