Miracle-dz/UniFAR-FTUs huggingface dataset:
Superinfection by PHYVV Alters the Recovery Process in PepGMV-Infected Pepper Plants

Geminiviruses are important plant pathogens that affect crops around the world. In some geminivirus–host interactions, infected plants show recovery, a phenomenon characterized by symptom disappearance in newly emerging leaves. In pepper–Pepper golden mosaic virus (PepGMV) interaction, the host recovery process involves a silencing mechanism that includes both post-transcriptional (PTGS) and transcriptional (TGS) gene silencing pathways. Under field conditions, PepGMV is frequently found in mixed infections with Pepper huasteco yellow vein virus (PHYVV), another bipartite begomovirus. Mixed infected plants generally show a synergetic phenomenon and do not present recovery. Little is known about the molecular mechanism of this interaction. In the present study, we explored the effect of superinfection by PHYVV on a PepGMV-infected pepper plant showing recovery. Superinfection with PHYVV led to (a) the appearance of severe symptoms, (b) an increase of the levels of PepGMV DNA accumulation, (c) a decrease of the relative methylation levels of PepGMV DNA, and (d) an increase of chromatin activation marks present in viral minichromosomes. Finally, using heterologous expression and silencing suppression reporter systems, we found that PHYVV REn presents TGS silencing suppressor activity, whereas similar experiments suggest that Rep might be involved in suppressing PTGS.
Current Status of Mumps Virus Infection: Epidemiology, Pathogenesis, and Vaccine

Mumps is an important childhood infectious disease caused by mumps virus (MuV). We reviewed the epidemiology, pathogenesis, and vaccine development of mumps. Previous studies were identified using the key words “mumps” and “epidemiology”, “pathogenesis” or “vaccine” in MEDLINE, PubMed, Embase, Web of Science, and Google Scholar. We excluded the articles that were not published in the English language, manuscripts without abstracts, and opinion articles from the review. The number of cases caused by MuV decreased steeply after the introduction of the mumps vaccine worldwide. In recent years, a global resurgence of mumps cases in developed countries and cases of aseptic meningitis caused by some mumps vaccine strains have renewed the importance of MuV infection worldwide. The performance of mumps vaccination has become an important issue for controlling mumps infections. Vaccine development and routine vaccination are still effective measures to globally reduce the incidence of mumps infections. During outbreaks, a third of MMR vaccine is recommended for groups of persons determined by public authorities.
Effect of bioactive glass air-abrasion on the wettability and osteoblast proliferation on sandblasted and acid-etched titanium surfaces.

The aim of this study was to evaluate the hydrophilicity, surface free energy, and proliferation and viability of human osteoblast-like MC3T3-E1 cells on sandblasted and acid-etched titanium surfaces after air-abrasion with 45S5 bioactive glass, zinc-containing bioactive glass, or inert glass. Sandblasted and acid-etched titanium discs were subjected to air-abrasion with 45S5 bioactive glass, experimental bioactive glass (Zn4), or inert glass. Water contact angles and surface free energy were evaluated. The surfaces were studied with preosteoblastic MC3T3-E1 cells. Air-abrasion with either type of glass significantly enhanced the hydrophilicity and surface free energy of the sandblasted and acid-etched titanium discs. The MC3T3-E1 cell number was higher for substrates air-abraded with Zn4 bioactive glass and similar to that observed on borosilicate coverslips (controls). Confocal laser scanning microscopy images showed that MC3T3-E1 cells did not spread as extensively on the sandblasted and acid-etched and bioactive glass-abraded surfaces as they did on control surfaces. However, for 45S5- and Zn4-treated samples, the cells spread most at the 24 h time point and changed their morphology to more spindle-like when cultured further. Air-abrasion with bioactive glass and inert glass was shown to have a significant effect on the wettability and surface free energy of the surfaces under investigation. Osteoblast cell proliferation on sandblasted and acid-etched titanium discs was enhanced by air-abrasion with 45S5 bioactive glass and experimental Zn4 bioactive glass compared with air-abrasion with inert glass or no air-abrasion.
Biochemical Characterization of QPX7728, a New Ultrabroad-Spectrum Beta-Lactamase Inhibitor of Serine and Metallo-Beta-Lactamases

QPX7728 is a new ultrabroad-spectrum inhibitor of serine and metallo-beta-lactamases (MBLs) from a class of cyclic boronates that gave rise to vaborbactam. The spectrum and mechanism of beta-lactamase inhibition by QPX7728 were assessed using purified enzymes from all molecular classes. QPX7728 inhibits class A extended-spectrum beta-lactamases (ESBLs) (50% inhibitory concentration [IC50] range, 1 to 3 nM) and carbapenemases such as KPC (IC50, 2.9 ± 0. ABSTRACT QPX7728 is a new ultrabroad-spectrum inhibitor of serine and metallo-beta-lactamases (MBLs) from a class of cyclic boronates that gave rise to vaborbactam. The spectrum and mechanism of beta-lactamase inhibition by QPX7728 were assessed using purified enzymes from all molecular classes. QPX7728 inhibits class A extended-spectrum beta-lactamases (ESBLs) (50% inhibitory concentration [IC50] range, 1 to 3 nM) and carbapenemases such as KPC (IC50, 2.9 ± 0.4 nM) as well as class C P99 (IC50 of 22 ± 8 nM) with a potency that is comparable to or higher than recently FDA-approved beta-lactamase inhibitors (BLIs) avibactam, relebactam, and vaborbactam. Unlike those other BLIs, QPX7728 is also a potent inhibitor of class D carbapenemases such as OXA-48 from Enterobacteriaceae and OXA enzymes from Acinetobacter baumannii (OXA-23/24/58, IC50 range, 1 to 2 nM) as well as MBLs such as NDM-1 (IC50, 55 ± 25 nM), VIM-1 (IC50, 14 ± 4 nM), and IMP-1 (IC50, 610 ± 70 nM). Inhibition of serine enzymes by QPX7728 is associated with progressive inactivation with a high-efficiency k2/K ranging from 6.3 × 104 (for P99) to 9.9 × 105 M−1 s−1 (for OXA-23). This inhibition is reversible with variable stability of the QPX7728-beta-lactamase complexes with target residence time ranging from minutes to several hours: 5 to 20 min for OXA carbapenemases from A. baumannii, ∼50 min for OXA-48, and 2 to 3 h for KPC and CTX-M-15. QPX7728 inhibited all tested serine enzymes at a 1:1 molar ratio. Metallo-beta-lactamases NDM, VIM, and IMP were inhibited by a competitive mechanism with fast-on–fast-off kinetics, with Kis of 7.5 ± 2.1 nM, 32 ± 14 nM, and 240 ± 30 nM for VIM-1, NDM-1, and IMP-1, respectively. QPX7728’s ultrabroad spectrum of BLI inhibition combined with its high potency enables combinations with multiple different beta-lactam antibiotics.
suddengains: An R package to identify sudden gains in longitudinal data

Sudden gains are large and stable improvements in an outcome variable between consecutive measurements, for example during a psychological intervention with multiple assessments. Researching these occurrences could help understand individual change processes in longitudinal data. Three criteria are generally used to identify sudden gains in psychological interventions. However, applying these criteria can be time consuming and prone to errors if not fully automated. Adaptations to these criteria and methodological decisions such as how multiple gains are handled vary across studies and are reported with different levels of detail. These problems limit the comparability of individual studies and make it hard to understand or replicate the exact methods used. The R package suddengains provides a set of tools to facilitate sudden gains research. This article illustrates how to use the package to identify sudden gains or sudden losses and how to extract descriptive statistics as well as exportable data files for further analysis. It also outlines how these analyses can be customised to apply adaptations of the standard criteria. The suddengains package therefore offers significant scope to improve the efficiency, reporting, and reproducibility of sudden gains research.
Differential activation of unconventional T cells, including iNKT cells, in alcohol-related liver disease.

BACKGROUND Liver is enriched in several innate-like unconventional T cells but their role in alcohol-related liver disease (ALD) is not fully understood. Studies in several acute alcohol feeding models but not in chronic alcoholic steatohepatitis (ASH) model have shown that invariant natural killer T (iNKT) cells play a pathogenic role in ALD. Here, we investigated the activation of iNKT cells in an intragastric (iG) infusion model of chronic ASH as well as the frequency and cytokine phenotype of three different unconventional T cells: iNKT, mucosal-associated invariant T (MAIT) and CD8+ CD161hi Vα7. 2- cells in peripheral blood of ALD patients. METHODS Hepatic iNKT cells were investigated using the iG model of chronic ASH that combine feeding of High-Cholesterol/High-Fat diet (HCFD) with intragastric feeding of ethanol diet (HCFD+iG Alc). Human iNKT, MAIT and CD8+ CD161hi Vα7. 2- cells were examined by flow cytometry in peripheral blood of patients with severe alcoholic hepatitis (SAH) and chronic alcoholics (ChA) and compared with healthy controls. RESULTS In the iG model of chronic ASH, IFNγ+ iNKT cells accumulate in their livers compared with pair-fed control mice and activated hepatic iNKT cells show high expression of Fas and FasL. Notably, IFNγ+ iNKT cells are also significantly increased in peripheral blood of ChA patients compared with SAH patients. MAIT cells are significantly reduced in all ALD patients, but CD8+ CD161hi Vα7. 2- cells are increased in SAH patients. Although, MAIT and CD8+ CD161hi Vα7. 2- cells displayed a similar cytokine production profile, IFNγ and TNFα production is significantly increased in SAH patients while significant IL-17A production is found in ChA patients. CONCLUSIONS We found that the three unconventional T cells are activated in ALD patients showing interesting differences in their frequency and cytokine production profile between SAH and ChA patients. In the iG murine model of chronic ASH, iNKT cells are also activated secreting pro-inflammatory cytokines suggesting their involvement in liver disease.
Comparison of Muscle-Specific Creatine Kinase (CK-MM) Gene Polymorphism (rs8111989) Among Professional, Amateur Athletes and Non-athlete Karatekas

Background: Identiﬁcation of genetic markers is one of the priority trends to perform in athletes for evaluation of their eﬃcacy. PreviousstudieshaverevealedthatCK-MMmaybeusedasavaluablemarkertoreﬂectthemagnitudeof skeletalmuscledestruction in response to exercise. Objectives: In this study we analyzed the frequency of rs8111989CK-MM polymorphism in karatekas to ﬁnd whether there is a dif-ference among professional, amateur athletes and non- karatekas. Methods: Distribution of allele and genotype frequencies of the muscle speciﬁc creatine kinase (CK-MM) gene A/G polymorphism was assessed in a survey among 275 athletes residing in state of Isfahan (86 professional karatekas (43 male and 43 female) and 86 amateurkaratekas(50maleand36female)and103non-athleteindividuals(50maleand53female). Bloodsamplesweretakenand genotyping was performed by restriction fragment length polymorphism (RFLP) approach. Statistical analyses carried out using SPSS software and data with P < 0.05 were considered to be signiﬁcant. Results: The CK-MM AG genotype frequency was signiﬁcantly higher in professional and amateur karate athletes and control subjects (AG genotype: 52.4% vs. AA genotype: 33.4%; GG genotype: 14.1%; χ 2 = 16.79, P < 0.05). Furthermore, the CK-MM genotype in the professional group (AA:31.3%, AG:56.9, GG:11.6) was diﬀerent of those observed for amateur karatekas (AA:32.5%, AG:43.0, GG:24.4)( χ 2 = 11.39; P = 0.003) and CK-MM genotype in the amateur group was also diﬀerent from non-athletes (AA:36%, AG: 56.3, GG: 7.7)( χ 2 = 11.39; P = 0.003). Conclusions: The CK-MM gene A/G polymorphism is associated with the physical performance levels of karatekas.
HPV genotype distribution and age correlation in a selected Italian population undergoing conization.

BACKGROUND Detection and genotyping of human papillomavirus (HPV) has gained increasing importance in cervical cancer prevention and treatment of cervical intraepithelial neoplasia (CIN). This study aims to determine the HPV type distribution in cervical specimens obtained from women diagnosed with CIN. We evaluated in a selected Italian population the distribution of HPV genotypes. METHODS Cervical samples were collected from women undergoing laser CO2 conization for high grade at Colposcopic Laser Surgery Unit of the Careggi University Hospital and at the Colposcopy Service of Local Health Unit Toscana Centro in Florence, Italy, between September 2014 and February 2017. HPV genotyping was performed using the LINEAR ARRAY® HPV Genotyping Test. RESULTS Three hundred and six patients were enrolled. HPV infection was detected on 244 samples (79.7%). A different rate of mono- and poly-infections was observed, with higher poly-infection rates in younger women. Moreover, depending on different age groups (clustered in 5-years interval from 22 to 69 years old) significant different distribution of HPV was fund as genotype, phylogenetic type and cancer-related risk. CONCLUSIONS Our results suggest that some physiological conditions (i.e. menopause), could influence selection and clearance of specific HPV genotypes. The results of this study represent the basis for supporting the HPV genotyping as clinical tool providing benefits in the management of women with high CIN grade.
The Complex Network between MYC Oncogene and microRNAs in Gastric Cancer: An Overview

Despite the advancements in cancer treatments, gastric cancer is still one of the leading causes of death worldwide. In this context, it is of great interest to discover new and more effective ways of treating this disease. Accumulated evidences have demonstrated the amplification of 8q24.21 region in gastric tumors. Furthermore, this is the region where the widely known MYC oncogene and different microRNAs are located. MYC deregulation is key in tumorigenesis in various types of tissues, once it is associated with cell proliferation, survival, and drug resistance. microRNAs are a class of noncoding RNAs that negatively regulate the protein translation, and which deregulation is related with gastric cancer development. However, little is understood about the interactions between microRNAs and MYC. Here, we overview the MYC role and its relationship with the microRNAs network in gastric cancer aiming to identify potential targets useful to be used in clinic, not only as biomarkers, but also as molecules for development of promising therapies.
Traitement préventif intermittent à la sulfadoxine-pyriméthamine chez la femme enceinte et effet sur le poids de naissance du bébé: application de la politique à 3 doses en zone urbaine au Sud Bénin en 2017

Introduction Le paludisme est un problème de santé publique majeur, responsable de nombreuses complications durant la grossesse parmi lesquelles le retard de croissance intra utérin et les hypotrophies. L'objectif de ce travail était de déterminer l'effet du respect des 3 doses du traitement préventif intermittent (TPI) à la sulfadoxine-pyrimétamine (SP) sur le poids de naissance des nouveau-nés de la zone sanitaire Cotonou II et III. Méthodes Il s'agit d'une étude transversale qui a porté sur 630 femmes en période post partum résidant dans la zone sanitaire Cotonou II-III et sélectionnées par une technique de sondage à deux degrés. Les données ont été recueillies par un questionnaire et une fiche de dépouillement. Pour l'analyse, les données ont été pondérées et nous avons utilisé l'analyse de variance pour la comparaison des moyennes et une comparaison de proportions avec le test de chi² assorti d'une estimation de la force de l'association par l'odds ratio (OR) et son intervalle de confiance à 95%. Résultats Le respect des 3 doses du TPI à la SP était de 34,08% (IC95%: [24,84% - 43,30%]). On note un gain significatif de poids de naissance de 264,5g (p < 0,001) chez les mères qui avaient reçu plus de 3 doses de SP et la probabilité d'avoir un bébé ayant un faible poids de naissance était plus faible (OR = 0,45; p = 0,001) chez ces mères comparativement à celles qui avaient reçu moins de 3 doses de sulfadoxine-pyriméthamine. Conclusion Cette étude révèle une faible observance de la nouvelle politique à 3 doses du traitement préventif intermittent à la sulfadoxine-pyriméthamine dans la zone sanitaire de Cotonou II et III, mais elle témoigne de son potentiel de contribution à la réduction du risque de faible poids de naissance. Des stratégies doivent donc être mises en œuvre pour renforcer son application en vue de la prévention du paludisme et de ses conséquences pour les cibles vulnérables.
Segregation of caffeine reward and aversion in the rat nucleus accumbens shell versus core

Caffeine, the most commonly consumed psychoactive drug in the world, is readily available in dietary sources, including soft drinks, chocolate, tea and coffee. However, little is known about the neural substrates that underlie caffeine's rewarding and aversive properties and what ultimately leads us to seek or avoid caffeine consumption. Using male Wistar rats in a place conditioning procedure, we show that systemic caffeine at a low intraperitoneal dose of 2 mg/kg (or 100 µM injected directly into the rostral, but not caudal, portion of the ventral tegmental area) produced conditioned place preferences. By contrast, high doses of systemic caffeine at 10 and 30 mg/kg produced conditioned place aversions. These aversions were not recapitulated by a caffeine analog restricted to the periphery. Both caffeine reward and aversion were blocked by systemic D1‐like receptor antagonism using SCH23390, while systemic D2‐like receptor antagonism with eticlopride had smaller effects on caffeine motivation. Most important, we demonstrated that pharmacological blockade of dopamine receptors using α‐flupenthixol injected into the nucleus accumbens shell, but not core, blocked caffeine‐conditioned place preferences. Conversely, α‐flupenthixol injected into the nucleus accumbens core, but not shell, blocked caffeine‐conditioned place aversions. Thus, our findings reveal two dopamine‐dependent and functionally dissociable mechanisms for processing caffeine motivation, which are segregated between nucleus accumbens subregions. These data provide novel evidence for the roles of the nucleus accumbens subregions in mediating approach and avoidance behaviours for caffeine.
A rare case of a closed loop obstruction due to epiploic appendage of the sigmoid colon

Abstract An internal hernia is a protrusion of viscera through a congenital or acquired defect in the mesentery of peritoneum. They account for <0.9% of all small bowel obstructions [1] and ~4% of obstructions due to hernias [2]. We present a rare case of closed loop obstruction secondary to a band adhesion traversing the lower abdomen from a sigmoid colon appendage epiploicae to the right pelvic wall. A 82-year-old woman presented to the emergency department with nausea, vomiting and worsening right sided abdominal pain for 24 h, on the background of previous pelvic radiation and hysterectomy for uterine cancer. She was subsequently found to have a closed loop obstruction with 30 cm of ischemic bowel strangulated by a band adhesion from a sigmoid colon appendage epiploicae to the right abdominal wall. The patient underwent a successful small bowel resection with primary anastomosis and made an uneventful recovery.
Sodium butyrate attenuated neuronal apoptosis via GPR41/Gβγ/PI3K/Akt pathway after MCAO in rats

Sodium butyrate, a short-chain fatty acid, is predominantly produced by gut microbiota fermentation of dietary fiber and serves as an important neuromodulator in the central nervous system. Recent experimental evidence has suggested that sodium butyrate may be an endogenous ligand for two orphan G protein-coupled receptors, GPR41 and GP43, which regulate apoptosis and inflammation in ischemia-related pathologies, including stroke. In the present study, we evaluated the potential efficacy and mechanism of action of short-chain fatty acids in a rat model of middle cerebral artery occlusion (MCAO). Fatty acids were intranasally administered 1 h post MCAO. Short-chain fatty acids, especially sodium butyrate, reduced infarct volume and improved neurological function at 24 and 72 h after MCAO. At 24 h, the effects of MCAO, increased apoptosis, were ameliorated after treatment with sodium butyrate, which increased the expressions of GPR41, PI3K and phosphorylated Akt. To confirm these mechanistic links and characterize the GPR active subunit, PC12 cells were subjected to oxygen–glucose deprivation and reoxygenation, and pharmacological and siRNA interventions were used to reverse efficacy. Taken together, intranasal administration of sodium butyrate activated PI3K/Akt via GPR41/Gβγ and attenuated neuronal apoptosis after MCAO.
Lung function and oxygen saturation after participation in Norseman Xtreme Triathlon

To examine evidence of exercise‐induced bronchoconstriction (EIB) defined as ≥10% reduction in forced expiratory volume in one second (FEV1) and exercise‐induced arterial hypoxemia (EIAH) defined as ≥4% reduction in oxygen saturation (SpO2) from before to after participation in the Norseman Xtreme Triathlon. Secondarily, to assess whether changes in FEV1 and SpO2 are related to respiratory symptoms, training volume, and race time.
Precise Identification of Cell and Tissue Features Important for Histopathologic Diagnosis by a Whole Slide Imaging System

Background: Previous studies have demonstrated the noninferiority of pathologists' interpretation of whole slide images (WSIs) compared to microscopic slides in diagnostic surgical pathology; however, to our knowledge, no published studies have tested analytical precision of an entire WSI system. Methods: In this study, five pathologists at three locations tested intra-system, inter-system/site, and intra- and inter-pathologist precision of the Aperio AT2 DX System (Leica Biosystems, Vista, CA, USA). Sixty-nine microscopic slides containing 23 different morphologic features suggested by the Digital Pathology Association as important to diagnostic pathology were identified and scanned. Each of 202 unique fields of view (FOVs) had 1–3 defined morphologic features, and each feature was represented in three different tissues. For intra-system precision, each site scanned 23 slides at three different times and one pathologist interpreted all FOVs. For inter-system/site precision, all 69 slides were scanned once at each of three sites, and FOVs from each site were read by one pathologist. To test intra- and inter-pathologist precision, all 69 slides were scanned at one site, FOVs were saved in three different orientations, and the FOVs were transferred to a different site. Three different pathologists then interpreted FOVs from all 69 slides. Wildcard (unscored) slides and washout intervals were included in each study. Agreement estimates with 95% confidence intervals were calculated. Results: Combined precision from all three studies, representing 606 FOVs in each of the three studies, showed overall intra-system agreement of 97.9%; inter-system/site agreement was 96%, intra-pathologist agreement was 95%, and inter-pathologist agreement was 94.2%. Conclusions: Pathologists using the Aperio AT2 DX System identified histopathological features with high precision, providing increased confidence in using WSI for primary diagnosis in surgical pathology.