Miracle-dz/UniFAR-FTUs huggingface dataset:
Rearing Trissolcus japonicus and Trissolcus mitsukurii for Biological Control of Halyomorpha halys

Simple Summary Halyomorpha halys is a severe agricultural pest of Asian origin, which threatens cultivation of vegetables and fruits worldwide. Classical biological control is foreseen as the most effective approach to reduce populations of H. halys. The egg parasitoid Trissolcus japonicus is the most important candidate biological control agent. Adventive populations of T. japonicus are already present in limited distributions in North America and in Europe. Trissolcus mitsukurii is a second Asian species that attacks H. halys and has been found in Northern Italy. Efficient laboratory rearing procedures of these biological control agents are needed for release programs to help control the pest. We present data that will help to optimize progeny production with minimal effort. Abstract Halyomorpha halys is a severe agricultural pest of Asian origin that has invaded many countries throughout the world. Pesticides are currently the favored control methods, but as a consequence of their frequent use, often disrupt Integrated Pest Management. Biological control with egg parasitoids is seen as the most promising control method over the long-term. Knowledge of the reproductive biology under laboratory conditions of the most effective candidates (Trissolcus japonicus and Trissolcus mitsukurii) for optimizing production for field releases is strongly needed. Rearing of these egg parasitoids was tested by offering three different host supply regimes using new emerged females and aged, host-deprived females in different combinations. Results showed a mean progeny per female ranging from 80 to 85 specimens for T. japonicus and from 63 to 83 for T. mitsukurii. Sex ratios were strongly female biased in all combinations and emergence rates exceeded 94% overall. Cumulative curves showed that longer parasitization periods beyond 10–14 days (under the adopted rearing regimes) will not lead to a significantly increase in progeny production. However, ageing females accumulate eggs in their ovaries that can be quickly laid if a sufficient number of host eggs are supplied, thus optimizing host resources. Our data showed that offering H. halys egg masses to host-deprived female Trissolcus once a week for three weeks allowed its eggs to accumulate in the ovary, providing the greatest number of offspring within a three week span.
Molecular epidemiology in the HIV and SARS-CoV-2 pandemics

Purpose of review The aim of this review was to compare and contrast the application of molecular epidemiology approaches for the improved management and understanding of the HIV versus SARS-CoV-2 epidemics. Recent findings Molecular biology approaches, including PCR and whole genome sequencing (WGS), have become powerful tools for epidemiological investigation. PCR approaches form the basis for many high-sensitivity diagnostic tests and can supplement traditional contact tracing and surveillance strategies to define risk networks and transmission patterns. WGS approaches can further define the causative agents of disease, trace the origins of the pathogen, and clarify routes of transmission. When coupled with clinical datasets, such as electronic medical record data, these approaches can investigate co-correlates of disease and pathogenesis. In the ongoing HIV epidemic, these approaches have been effectively deployed to identify treatment gaps, transmission clusters and risk factors, though significant barriers to rapid or real-time implementation remain critical to overcome. Likewise, these approaches have been successful in addressing some questions of SARS-CoV-2 transmission and pathogenesis, but the nature and rapid spread of the virus have posed additional challenges. Summary Overall, molecular epidemiology approaches offer unique advantages and challenges that complement traditional epidemiological tools for the improved understanding and management of epidemics.
Recent Updates and Advances in the Use of Glycated Albumin for the Diagnosis and Monitoring of Diabetes and Renal, Cerebro- and Cardio-Metabolic Diseases

Diabetes mellitus is a heterogeneous and dysmetabolic chronic disease in which the laboratory plays a fundamental role, from diagnosis to monitoring therapy and studying complications. Early diagnosis and good glycemic control should start as early as possible to delay and prevent metabolic and cardio-vascular complications secondary to this disease. Glycated hemoglobin is currently used as the reference parameter. The accuracy of the glycated hemoglobin dosage may be compromised in subjects suffering from chronic renal failure and terminal nephropathy, affected by the reduction in the survival of erythrocytes, with consequent decrease in the time available for glucose to attach to the hemoglobin. In the presence of these renal comorbidities as well as hemoglobinopathies and pregnancy, glycated hemoglobin is not reliable. In such conditions, dosage of glycated albumin can help. Glycated albumin is not only useful for short-term diagnosis and monitoring but predicts the risk of diabetes, even in the presence of euglycemia. This protein is modified in subjects who do not yet have a glycemic alteration but, as a predictive factor, heralds the risk of diabetic disease. This review summarizes the importance of glycated albumin as a biomarker for predicting and stratifying the cardiovascular risk linked to multiorgan metabolic alterations.
The peroxisome proliferator-activated receptor gamma (PPARγ) agonist, rosiglitazone, ameliorates neurofunctional and neuroinflammatory abnormalities in a rat model of Gulf War Illness

Background Gulf War (GW) Illness (GWI) is a debilitating condition with a complex constellation of immune, endocrine and neurological symptoms, including cognitive impairment, anxiety and depression. We studied a novel model of GWI based on 3 known common GW exposures (GWE): (i) intranasal lipopolysaccharide, to which personnel were exposed during desert sand storms; (ii) pyridostigmine bromide, used as prophylaxis against chemical warfare; and (iii) chronic unpredictable stress, an inescapable element of war. We used this model to evaluate prophylactic treatment with the PPARγ agonist, rosiglitazone (ROSI). Methods Rats were subjected to the three GWE for 33 days. In series 1 and 2, male and female GWE-rats were compared to naïve rats. In series 3, male rats with GWE were randomly assigned to prophylactic treatment with ROSI (GWE-ROSI) or vehicle. After the 33-day exposures, three neurofunctional domains were evaluated: cognition (novel object recognition), anxiety-like behaviors (elevated plus maze, open field) and depression-like behaviors (coat state, sucrose preference, splash test, tail suspension and forced swim). Brains were analyzed for astrocytic and microglial activation and neuroinflammation (GFAP, Iba1, tumor necrosis factor and translocator protein). Neurofunctional data from rats with similar exposures were pooled into 3 groups: naïve, GWE and GWE-ROSI. Results Compared to naïve rats, GWE-rats showed significant abnormalities in the three neurofunctional domains, along with significant neuroinflammation in amygdala and hippocampus. There were no differences between males and females with GWE. GWE-ROSI rats showed significant attenuation of neuroinflammation and of some of the neurofunctional abnormalities. Conclusion This novel GWI model recapitulates critical neurofunctional abnormalities reported by Veterans with GWI. Concurrent prophylactic treatment with ROSI was beneficial in this model.
Pivotal Role of Fatty Acid Synthase in c-MYC Driven Hepatocarcinogenesis

Hepatocellular carcinoma (HCC) is a deadly form of liver malignancy with limited treatment options. Amplification and/or overexpression of c-MYC is one of the most frequent genetic events in human HCC. The mammalian target of Rapamycin Complex 1 (mTORC1) is a major functional axis regulating various aspects of cellular growth and metabolism. Recently, we demonstrated that mTORC1 is necessary for c-Myc driven hepatocarcinogenesis as well as for HCC cell growth in vitro. Among the pivotal downstream effectors of mTORC1, upregulation of Fatty Acid Synthase (FASN) and its mediated de novo lipogenesis is a hallmark of human HCC. Here, we investigated the importance of FASN on c-Myc-dependent hepatocarcinogenesis using in vitro and in vivo approaches. In mouse and human HCC cells, we found that FASN suppression by either gene silencing or soluble inhibitors more effectively suppressed proliferation and induced apoptosis in the presence of high c-MYC expression. In c-Myc/Myeloid cell leukemia 1 (MCL1) mouse liver tumor lesions, FASN expression was markedly upregulated. Most importantly, genetic ablation of Fasn profoundly delayed (without abolishing) c-Myc/MCL1 induced HCC formation. Liver tumors developing in c-Myc/MCL1 mice depleted of Fasn showed a reduction in proliferation and an increase in apoptosis when compared with corresponding lesions from c-Myc/MCL1 mice with an intact Fasn gene. In human HCC samples, a significant correlation between the levels of c-MYC transcriptional activity and the expression of FASN mRNA was detected. Altogether, our study indicates that FASN is an important effector downstream of mTORC1 in c-MYC induced HCC. Targeting FASN may be helpful for the treatment of human HCC, at least in the tumor subset displaying c-MYC amplification or activation.
Genetic Spectrum of Syndromic and Non-Syndromic Hearing Loss in Pakistani Families

The current molecular genetic diagnostic rates for hereditary hearing loss (HL) vary considerably according to the population background. Pakistan and other countries with high rates of consanguineous marriages have served as a unique resource for studying rare and novel forms of recessive HL. A combined exome sequencing, bioinformatics analysis, and gene mapping approach for 21 consanguineous Pakistani families revealed 13 pathogenic or likely pathogenic variants in the genes GJB2, MYO7A, FGF3, CDC14A, SLITRK6, CDH23, and MYO15A, with an overall resolve rate of 61.9%. GJB2 and MYO7A were the most frequently involved genes in this cohort. All the identified variants were either homozygous or compound heterozygous, with two of them not previously described in the literature (15.4%). Overall, seven missense variants (53.8%), three nonsense variants (23.1%), two frameshift variants (15.4%), and one splice-site variant (7.7%) were observed. Syndromic HL was identified in five (23.8%) of the 21 families studied. This study reflects the extreme genetic heterogeneity observed in HL and expands the spectrum of variants in deafness-associated genes.
Contrasting patterns of local richness of seedlings, saplings, and trees may have implications for regeneration in rainforest remnants

Remnants of lowland rain forest remain following deforestation, but the longer‐term effects of fragmentation remain poorly understood, partly due to the long generation times of trees. We study rain forest trees in three size classes: seedlings (<1 cm dbh), saplings (1–5 cm dbh), and trees (>5 cm) that broadly reflect pre‐ and post‐fragmentation communities, and we examine the impacts of fragmentation on forest regeneration in Sabah, Malaysian Borneo. We found that seedling richness (measured as the number of genera per plot) in fragments was about 30 percent lower than in plots in undisturbed forest, and about 20 percent lower than in an extensive tract of selectively logged forest, providing evidence of recruitment declines in fragments. Seedling richness was lowest in small, isolated, and disturbed fragments, potentially signaling an extinction debt given that these fragmentation impacts were not observed in trees. Unlike seedlings, saplings showed no declines in richness in fragments, suggesting that density dependent mortality (where rare individuals have a higher survival rate) and/or year‐to‐year variation in which species are recruiting could potentially compensate for the reductions in seedling richness we observed. Longer‐term studies are required to determine whether sporadic or failed recruitment in small fragments will eventually translate into reduced richness of mature trees, or whether the processes that currently retain high sapling richness will continue in fragments.
Effect of Dapagliflozin on Clinical Outcomes in Patients with Chronic Kidney Disease, With and Without Cardiovascular Disease.

Background: Dapagliflozin reduces the risk of end-stage renal disease in patients with chronic kidney disease. We examined the relative risk of cardiovascular and kidney events in these patients and the effect of dapagliflozin on either type of event, taking account of history of cardiovascular disease. Methods: In the DAPA-CKD trial (Dapagliflozin And Prevention of Adverse Outcomes in Chronic Kidney Disease), 4304 participants with chronic kidney disease were randomized to dapagliflozin 10 mg once daily or placebo. The primary endpoint was a composite of sustained decline in estimated GFR ≥50%, end-stage kidney disease, or kidney or cardiovascular death. The secondary endpoints were a kidney composite outcome (primary endpoint, minus cardiovascular death), the composite of hospitalization for heart failure or cardiovascular death and all-cause death. In a prespecified subgroup analysis, we divided patients into primary and secondary prevention subgroups according to history of cardiovascular disease. Results: Secondary prevention patients (n=1610; 37.4%) were older, more often male, had a higher blood pressure and body-mass index, and were more likely to have diabetes. Mean estimated glomerular filtration rate and median urinary albumin-to-creatinine ratio was similar in the primary and secondary prevention groups. The rates of adverse cardiovascular outcomes were higher in the secondary prevention group, but kidney failure occurred at the same rate in the primary and secondary prevention groups. Dapagliflozin reduced the risk of the primary composite outcome to a similar extent in both the primary (HR, 0.61 [95% CI, 0.48-0.78]) and secondary (0.61, 0.47-0.79) prevention groups (P-interaction=0.90). This was also true for the composite of heart failure hospitalization or cardiovascular death (0.67, 0.40-1.13 versus 0.70, 0.52-0.94, respectively, P-interaction=0.88), and all-cause (0.63, 0.41-0.98 versus 0.70, 0.51-0.95, respectively, P-interaction=0.71). Rates of adverse events were low overall and did not differ between patients with and without cardiovascular disease. Conclusions: Dapagliflozin reduced the risk of kidney failure, death from cardiovascular causes or hospitalization for heart failure, and prolonged survival, in people with chronic kidney disease, with or without type 2 diabetes, independently of the presence of concomitant cardiovascular disease Clinical Trial Registration: URL: https://clinicaltrials.gov Unique Identifier: NCT03036150.
Duchenne muscular dystrophy (DMD) cardiomyocyte-secreted exosomes promote the pathogenesis of DMD-associated cardiomyopathy

ABSTRACT Cardiomyopathy is a leading cause of early mortality in Duchenne muscular dystrophy (DMD). There is a need to gain a better understanding of the molecular pathogenesis for the development effective therapies. Exosomes (exo) are secreted vesicles and exert effects via their RNA, lipid and protein cargo. The role of exosomes in disease pathology is unknown. Exosomes derived from stem cells have demonstrated cardioprotection in the murine DMD heart. However, it is unknown how the disease status of the donor cell type influences exosome function. Here, we sought to determine the phenotypic responses of DMD cardiomyocytes (DMD-iCMs) after long-term exposure to DMD cardiac exosomes (DMD-exo). DMD-iCMs were vulnerable to stress, evidenced by production of reactive oxygen species, the mitochondrial membrane potential and cell death levels. Long-term exposure to non-affected exosomes (N-exo) was protective. By contrast, long-term exposure to DMD-exo was not protective, and the response to stress improved with inhibition of DMD-exo secretion in vitro and in vivo. The microRNA (miR) cargo, but not exosome surface peptides, was implicated in the pathological effects of DMD-exo. Exosomal surface profiling revealed N-exo peptides associated with PI3K-Akt signaling. Transcriptomic profiling identified unique changes with exposure to either N- or DMD-exo. Furthermore, DMD-exo miR cargo regulated injurious pathways, including p53 and TGF-beta. The findings reveal changes in exosomal cargo between healthy and diseased states, resulting in adverse outcomes. Here, DMD-exo contained miR changes, which promoted the vulnerability of DMD-iCMs to stress. Identification of these molecular changes in exosome cargo and effectual phenotypes might shed new light on processes underlying DMD cardiomyopathy. This article has an associated First Person interview with the first author of the paper. Summary: This study examines the consequential effects of exposure to diseased exosomes in a cell model of Duchenne muscular dystrophy (DMD). The findings support a detrimental role for long-term DMD cardiac exosome exposure.
The Sogou System for Blizzard Challenge 2020

In this paper, we introduce the text-to-speech system from Sogou team submitted to Blizzard Challenge 2020. The goal of this year’s challenge is to build a natural Mandarin Chinese speech synthesis system from the 10-hours corpus by a native Chinese male speaker. We will discuss the major modules of the submitted system: (1) the front-end module to analyze the pronunciation and prosody of text; (2) the FastSpeech-based sequence-to-sequence acoustic model to predict acoustic features; (3) the WaveRNN based neural vocoder to reconstruct waveforms. Evaluation results provided by the challenge organizer are also discussed
Repurposing p97 inhibitors for chemical modulation of the bacterial ClpB–DnaK bichaperone system

The ClpB–DnaK bichaperone system reactivates aggregated cellular proteins and is essential for survival of bacteria, fungi, protozoa, and plants under stress. AAA+ ATPase ClpB is a promising target for the development of antimicrobials because a loss of its activity is detrimental for survival of many pathogens and no apparent ClpB orthologs are found in metazoans. We investigated ClpB activity in the presence of several compounds that were previously described as inhibitor leads for the human AAA+ ATPase p97, an antitumor target. We discovered that N2,N4-dibenzylquinazoline-2,4-diamine (DBeQ), the least potent among the tested p97 inhibitors, binds to ClpB with a Kd∼60 μM and inhibits the casein-activated, but not the basal, ATPase activity of ClpB with an IC50∼5 μM. The remaining p97 ligands, which displayed a higher affinity toward p97, did not affect the ClpB ATPase. DBeQ also interacted with DnaK with a Kd∼100 μM and did not affect the DnaK ATPase but inhibited the DnaK chaperone activity in vitro. DBeQ inhibited the reactivation of aggregated proteins by the ClpB–DnaK bichaperone system in vitro with an IC50∼5 μM and suppressed the growth of cultured Escherichia coli. The DBeQ-induced loss of E. coli proliferation was exacerbated by heat shock but was nearly eliminated in a ClpB-deficient E. coli strain, which demonstrates a significant selectivity of DBeQ toward ClpB in cells. Our results provide chemical validation of ClpB as a target for developing novel antimicrobials. We identified DBeQ as a promising lead compound for structural optimization aimed at selective targeting of ClpB and/or DnaK.
Factors Associated With Non-enrollment of Center-Based Cardiovascular Rehabilitation Program Among Transient Ischemic Attack or Mild Stroke Patients: A MIXED-METHOD RETROSPECTIVE STUDY.

PURPOSE Cardiovascular rehabilitation programs (CRPs) are effective in secondary stroke prevention, yet the enrollment rate is suboptimal. This study aims to identify demographic and clinical factors and patient-reported reasons for non-enrollment in a center-based outpatient CRP among patients with transient ischemic attack (TIA) or mild stroke. METHODS This mixed-method retrospective chart review was conducted in an outpatient CRP affiliated with a tertiary care hospital in Canada from January 2009 to October 2017. A total of 621 patients with TIA or mild stroke were included. Multiple logistic regression was used to determine the relationship between demographic and clinical predictors with non-enrollment. A thematic analysis of multidisciplinary progress notes was done for the non-enrollment subgroup of patients to understand the patient-reported reasons. RESULTS The non-enrollment rate was 42%. Travel distance to CRP (OR = 1.024; 95% CI, 1.010-1.038), age (OR = 1.023; 95% CI, 1.004-1.042), and current smoking status (OR = 1.935; 95% CI, 1.230-3.042) were associated with non-enrollment. The patient-reported reasons for non-enrollment were occurrence of new medical events and comorbidities, their perceptions of health and CRP, transportation, work/time conflict, and distance. CONCLUSIONS This study found that patients with TIA or mild stroke who were older, lived farther from the CRP center, or were current smokers were less likely to enroll in a CRP. The present findings may help clinicians identify patients unlikely to enroll in a CRP and allow the implementation of interventions focused on health education and physical activity to improve enrollment. Future research should validate these factors in multiple settings using prospective mixed methods so that interventions can be developed to address non-enrollment in the CRP.
Accurate Offline Asynchronous Detection of Individual Finger Movement From Intracranial Brain Signals Using a Novel Multiway Approach

Asynchronous motor Brain Computer Interfacing (BCI) is characterized by the continuous decoding of intended muscular activity from brain signals. Such applications have gained widespread interest for enabling users to issue commands volitionally. In conventional motor BCIs features extracted from brain signals are concatenated into vector- or matrix-based (or one-/two-way) representations. Nevertheless, when accounting for the original multimodal or multiway signal structure, decoding performance has been shown to improve jointly with result interpretability. However, as multiway decoders are notorious for the extensive computational cost to train them, conventional ones are still preferred. To curb this limitation, we introduce a novel multiway classifier, called Block-Term Tensor Classifier that inherits the improved accuracy of multiway methods while providing fast training. We show that it can outperform state-of-the-art multiway and two-way Linear Discriminant Analysis classifiers in asynchronous detection of individual finger movements from intracranial recordings, an essential feature to achieve a sense of dexterity with hand prosthetics and exoskeletons.