Miracle-dz/UniFAR-FTUs huggingface dataset:
Comparative transcriptomic analysis reveal genes involved in the pathogenicity increase of Streptococcus suis epidemic strains

ABSTRACT Streptococcus suis epidemic strains were responsible for two outbreaks in China and possessed increased pathogenicity which was featured prominently by inducing an excessive inflammatory response at the early phase of infection. To discover the critical genes responsible for the pathogenicity increase of S. suis epidemic strains, the genome-wide transcriptional profiles of epidemic strain SC84 were investigated at the early phase of interaction with BV2 cells. The overall low expression levels of 89K pathogenicity island (PAI) and 129 known virulence genes in the SC84 interaction groups indicated that its pathogenicity increase should be attributed to novel mechanisms. Using highly pathogenic strain P1/7 and intermediately pathogenic strain 89–1591 as controls, 11 pathogenicity increase crucial genes (PICGs) and 38 pathogenicity increase-related genes (PIRGs) were identified in the SC84 incubation groups. The PICGs encoded proteins related to the methionine biosynthesis/uptake pathway and played critical roles in the pathogenicity increase of epidemic strains. A high proportion of PIRGs encoded surface proteins related to host cell adherence and immune escape, which may be conducive to the pathogenicity increase of epidemic strains by rapidly initiating infection. The fact that none of PICGs and PIRGs belonged to epidemic strain-specific gene indicated that the pathogenicity increase of epidemic strain may be determined by the expression level of genes, rather than the presence of them. Our results deepened the understanding on the mechanism of the pathogenicity increase of S. suis epidemic strains and provided novel approaches to control the life-threatening infections of S. suis epidemic strains.
Gene expression and phytohormone levels in the asymptomatic and symptomatic phases of infection in potato tubers inoculated with Dickeya solani

Dickeya solani is a soft rot bacterium with high virulence. In potato, D. solani, like the other potato-infecting soft rot bacteria, causes rotting and wilting of the stems and rotting of tubers in the field and in storage. Latent, asymptomatic infections of potato tubers are common in harvested tubers, and if the storage conditions are not optimal, the latent infection turns into active rotting. We characterized potato gene expression in artificially inoculated tubers in nonsymptomatic, early infections 1 and 24 hours post-inoculation (hpi) and compared the results to the response in symptomatic tuber tissue 1 week (168 hpi) later with RNA-Seq. In the beginning of the infection, potato tubers expressed genes involved in the detection of the bacterium through pathogen-associated molecular patterns (PAMPs), which induced genes involved in PAMPs-triggered immunity, resistance, production of pathogenesis-related proteins, ROS, secondary metabolites and salicylic acid (SA) and jasmonic acid (JA) biosynthesis and signaling genes. In the symptomatic tuber tissue one week later, the PAMPs-triggered gene expression was downregulated, whereas primary metabolism was affected, most likely leading to free sugars fueling plant defense but possibly also aiding the growth of the pathogen. In the symptomatic tubers, pectic enzymes and cell wall-based defenses were activated. Measurement of hormone production revealed increased SA concentration and almost no JA in the asymptomatic tubers at the beginning of the infection and high level of JA and reduced SA in the symptomatic tubers one week later. These findings suggest that potato tubers rely on different defense strategies in the different phases of D. solani infection even when the infection takes place in fully susceptible plants incubated in conditions leading to rotting. These results support the idea that D. solani is a biotroph rather than a true necrotroph.
Synergistic Cytotoxic and Antimigratory Effect of Brazilein and Doxorubicin on HER2-Overexpressing Cells

Objective: The present research aims to report cytotoxic and antimigratory activities of the oxidized form of brazilin, i.e., brazilein, and the effects of the combination of brazilein-doxorubicin on MCF-7/HER2 cells. Methods: The MTT assay was conducted to test the cytotoxic activity, while flow cytometry with PI and PI-annexin V staining were respectively performed for cell cycle and apoptosis analyses. Migration and invasion analyses were assessed via Boyden chamber assay, while HER2, Rac1, p120, MMP2, and MMP9 protein levels were determined by immunoblotting and gelatin zymography. Molecular docking of ligands with HER2, Src, PI3Kα, PI3KΔ, and PI3Kγ proteins was evaluated using MOE 2010. Results: The MTT assay showed that the IC50 value of brazilein against MCF-7/HER2 cells was 51 ± 2.1 µM. Moreover, brazilein and its combination with doxorubicin-induced G2/M accumulation and apoptosis. Combination of brazilein-doxorubicin inhibited cell migration and tended to decrease HER2, Rac1, p120, MMP2, and MMP9 protein expression levels. Based on our molecular docking study, the docking score of brazilein with PI3Kγ is comparable to that of the native ligand. Conclusion: Taken together, a combination of brazilein-doxorubicin exhibited synergistic cytotoxic and antimigratory effects on MCF-7/HER2 cells.
Predictors of recurrence after catheter ablation and electrical cardioversion of atrial fibrillation: an umbrella review of meta-analyses

Abstract Aims The recurrence rates after catheter ablation (CA) and direct current (DC) cardioversion remain high, although they have been established treatments of rhythm control of atrial fibrillation (AF). This umbrella review systematically appraises published meta-analyses of both observational and randomized controlled trials (RCTs) for the association of risk and protective factors for arrhythmia recurrence after CA and DC cardioversion of AF. Methods and results Three bibliographic databases were searched up to June 2021. Evidence of association was rated as convincing, highly suggestive, suggestive, weak, or not significant with respect to observational studies and as high, moderate, low, or very low with respect to RCTs, according to established criteria. Thirty-one meta-analyses were included. Of the 28 associations between CA and the risk of arrhythmia recurrence, none presented convincing evidence, and only the time from diagnosis to ablation over 1 year provided highly suggestive evidence. The association between hypertension and metabolic profile provided suggestive evidence. The associations of Class IC and III antiarrhythmic drugs use with the recurrence after DC cardioversion were supported by an intermediate level of evidence. Conclusion Although AF is a major health issue, few risk- and protective factors for AF recurrence have been identified. None of these factors examined were supported by convincing evidence, whereas established factors such as female gender and left atrial volume showed only weak association. An early CA strategy combined with treatment of metabolic syndrome and hypertension prior to CA may reduce the risk of arrhythmia recurrence. The use of antiarrhythmics can increase the success rate of DC cardioversion. Systematic review registration PROSPERO registry number: CRD42021270613.
Comparative Study of Helicobacter Pylori Resistance to Clarithromycin and Metronidazole and Its Association with Epidemiological Factors in A Moroccan Population

Objective: Knowledge of local antibiotic resistance is crucial to the adaption of the effective empirical first-line treatment for Helicobacter Pylori (H. pylori) infection. This study aimed to evaluate the prevalence of H. pylori resistance to clarithromycin and compare it with that of metronidazole, and highlight the impact of epidemiological factors and gastric lesions severity on H. pylori resistance. Methods: The susceptibility to clarithromycin of 96 isolates was determined by PCR-RFLP and the susceptibility to metronidazole of 185 isolates was determined by classic PCR. Result: Our results showed that the prevalence of H. pylori resistance to clarithromycin (‎14.6%) was low compared to that recorded with metronidazole (‎62.7%). Moreover, we remarked that 7.3% of isolates were co-resistant to both antibiotics. The assessment of epidemiological factors’ impact on the resistance to studied antibiotics has revealed no association. Besides, our results had demonstrated that the metronidazole and clarithromycin resistance was not related to the severity of gastric lesions. Conclusion: In our population, clarithromycin seems to be an effective antibiotic as long as the resistance rate of H. pylori is low. In contrast to metronidazole, it appears that this antibiotic will lose its efficacy, due to the high rate of resistance among our population. Therefore, each population must conduct their epidemiologic studies separately to survey the resistance profile of strains and choose the appropriate antibiotic, in order to avoid the failure of H. pylori eradication and the development of severe gastric diseases.
Cytology, High-Risk Human Papillomavirus Testing and Serum CA19-9 in a Large Cohort of Patients with Invasive Cervical Adenocarcinomas: Correlation with a New Pathogenetic Classification

Aims: This study aims to investigate the screening value of cytology, high-risk human papillomavirus (hrHPV) testing and serum CA19-9 in cervical adenocarcinomas. Materials and Methods: We employed HPV RNA in situ hybridization and immunohistochemistry to reclassify 209 cervical adenocarcinomas according to the International Endocervical Adenocarcinoma Criteria and Classification (IECC). We analyzed the diagnostic value of cytology, hrHPV testing and serum CA19-9 in these tumors and their detection variance among IECC histotypes. Results: We found that the sensitivity of cytology or hrHPV test alone was 74.1% (129/174) or 72% (131/182), respectively. Non-HPV related adenocarcinoma showed a lower detection rate of cytology (60%, 27/45 vs. 79.1%, 102/129, p=0.017) or hrHPV testing (9.8%, 4/41 vs. 90.1%, 127/141, p<0.0001), compared to HPV-related adenocarcinomas. The cytology and hrHPV co-testing significantly demonstrated a higher sensitivity (151/165, 91.5%) than single test alone (p<0.001). Nevertheless, the sensitivity of co-testing was substantially lower for gastric-type adenocarcinoma (GAC) (74.1%, 20/27) than that for non-GAC (94.9%, 131/138) (p=0.001). Serum CA19-9 (>40 U/mL) identified 44.1% (15/34) GACs including 75% (6/8) that were missed by co-testing, much higher than for non-GACs (10.7%, 19/177; p<0.001). The combination of cytology, hrHPV test and serum CA19-9 enhanced the detection rate of GACs (92.9%, 26/28). Conclusion: We conclude that cytology and hrHPV co-testing is not very effective for non-HPV related adenocarcinoma, particularly for GAC. As such, additional serum CA19-9 should be given in women with potential cancer risks.
Inpatient physical activity across a large university city hospital: a behavioral mapping study

ABSTRACT Background Physical inactivity is common during hospitalization. Physical activity has been described in different inpatient populations but never across a hospital. Purpose To describe inpatient movement behavior and associated factors throughout a single university hospital. Methods A prospective observational study was performed. Patients admitted to clinical wards were included. Behavioral mapping was undertaken for each participant between 9AM and 4PM. The location, physical activity, daily activity, and company of participants were described. Barriers to physical activity were examined using linear regression analyses. Results In total, 345 participants from 19 different wards were included. The mean (SD) age was 61 (16) years and 57% of participants were male. In total, 65% of participants were able to walk independently. On average participants spent 86% of observed time in their room and 10% of their time moving. A physiotherapist or occupational therapist was present during 1% of the time, nursing staff and family were present 11% and 13%, respectively. Multivariate regression analysis showed the presence of an intravenous line (p = .039), urinary catheter (p = .031), being female (p = .034), or being dependent on others for walking (p = .016) to be positively associated with the time spent in bed. Age > 65, undergoing surgery, receiving encouragement by a nurse or physician, reporting a physical complaint or pain were not associated with the time spent in bed (P > .05). Conclusion As family members and nursing staff spend more time with patients than physiotherapists or occupational therapists, increasing their involvement might be an important next step in the promotion of physical activity.
Neuropeptide S (NPS) neurons: Parabrachial identity and novel distributions

Neuropeptide S (NPS) increases wakefulness. A small number of neurons in the brainstem express Nps. These neurons are located in or near the parabrachial nucleus (PB), but we know very little about their ontogeny, connectivity, and function. To identify Nps‐expressing neurons within the molecular framework of the PB region, we used in situ hybridization, immunofluorescence, and Cre‐reporter labeling in mice. The primary concentration of Nps‐expressing neurons borders the lateral lemniscus at far‐rostral levels of the lateral PB. Caudal to this main cluster, Nps‐expressing neurons scatter through the PB and form a secondary concentration medial to the locus coeruleus (LC). Most Nps‐expressing neurons in the PB region are Atoh1‐derived, Foxp2‐expressing, and mutually exclusive with neurons expressing Calca or Lmx1b. Among Foxp2‐expressing PB neurons, those expressing Nps are distinct from intermingled subsets expressing Cck or Pdyn. Examining Nps Cre‐reporter expression throughout the brain identified novel populations of neurons in the nucleus incertus, anterior hypothalamus, and lateral habenula. This information will help focus experimental questions about the connectivity and function of NPS neurons.
Inflammation and cardiovascular status impact midazolam pharmacokinetics in critically ill children: An observational, prospective, controlled study

Altered physiology caused by critical illness may change midazolam pharmacokinetics and thereby result in adverse reactions and outcomes in this vulnerable patient population. This study set out to determine which critical illness‐related factors impact midazolam pharmacokinetics in children using population modeling. This was an observational, prospective, controlled study of children receiving IV midazolam as part of routine care. Children recruited into the study were either critically‐ill receiving continuous infusions of midazolam or otherwise well, admitted for elective day‐case surgery (control) who received a single IV bolus dose of midazolam. The primary outcome was to determine the population pharmacokinetics and identify covariates that influence midazolam disposition during critical illness. Thirty‐five patients were recruited into the critically ill arm of the study, and 54 children into the control arm. Blood samples for assessing midazolam and 1‐OH‐midazolam concentrations were collected opportunistically (critically ill arm) and in pre‐set time windows (control arm). Pharmacokinetic modeling demonstrated a significant change in midazolam clearance with acute inflammation (measured using C‐Reactive Protein), cardio‐vascular status, and weight. Simulations predict that elevated C‐Reactive Protein and compromised cardiovascular function in critically ill children result in midazolam concentrations up to 10‐fold higher than in healthy children. The extremely high concentrations of midazolam observed in some critically‐ill children indicate that the current therapeutic dosing regimen for midazolam can lead to over‐dosing. Clinicians should be aware of this risk and intensify monitoring for oversedation in such patients.
Housing and loneliness among individuals with serious mental illnesses

Background: People with serious mental illnesses (SMI) have higher levels of loneliness than the general population. Furthermore, people with SMI tend to be less satisfied with their housing and tend to move more frequently. Aim: This study aims to examine relationships between housing variables (whom they live with, duration of residence, and satisfaction) and loneliness among individuals with SMI. Methods: Data were collected from 188 adults with SMI in greater Philadelphia area. Classification and Regression Trees (CART) were used to examine whether whom they live with, duration of residence, and housing satisfaction were associated with loneliness. Results: Housing satisfaction was found to be the most prominent predictor of loneliness. Those who were unsatisfied with their overall housing conditions always had the highest level of loneliness, regardless of other factors. Even if they were satisfied with their housing conditions, their loneliness was higher if they had just moved to the new residence. Participants had lower loneliness the longer they lived in a residence and had the lowest loneliness levels after about three years. Conclusion: Housing is associated with loneliness among people with SMI. Psychiatric service providers should increase support to factors contributing to housing satisfaction and duration of residence, including active engagement in the community.
Efficacy of Artemether-Lumefantrine and Dihydroartemisinin-Piperaquine for the Treatment of Uncomplicated Plasmodium falciparum Malaria among Children in Western Kenya, 2016 to 2017

Antimalarial resistance threatens global malaria control efforts. The World Health Organization (WHO) recommends routine antimalarial efficacy monitoring through a standardized therapeutic efficacy study (TES) protocol. ABSTRACT Antimalarial resistance threatens global malaria control efforts. The World Health Organization (WHO) recommends routine antimalarial efficacy monitoring through a standardized therapeutic efficacy study (TES) protocol. From June 2016 to March 2017, children with uncomplicated P. falciparum mono-infection in Siaya County, Kenya were enrolled into a standardized TES and randomized (1:1 ratio) to a 3-day course of artemether-lumefantrine (AL) or dihydroartemisinin-piperaquine (DP). Efficacy outcomes were measured at 28 and 42 days. A total of 340 children were enrolled. All but one child cleared parasites by day 3. PCR-corrected adequate clinical and parasitological response (ACPR) was 88.5% (95% CI: 80.9 to 93.3%) at day 28 for AL and 93.0% (95% CI: 86.9 to 96.4%) at day 42 for DP. There were 9.6 times (95% CI: 3.4 to 27.2) more reinfections in the AL arm compared to the DP arm at day 28, and 3.1 times (95% CI: 1.9 to 4.9) more reinfections at day 42. Both AL and DP were efficacious (per WHO 90% cutoff in the confidence interval) and well tolerated for the treatment of uncomplicated malaria in western Kenya, but AL efficacy appears to be waning. Further efficacy monitoring for AL, including pharmacokinetic studies, is recommended.
Intestinal phages interact with bacteria and are involved in human diseases

ABSTRACT Phages are the most abundant and diverse biological entities on Earth and exert specific effects on bacterial hosts. The coexistence of phages and bacteria in the intestinal tract is dynamic and interdependent. Phages are involved in maintaining the stability and composition of the bacterial community, and an imbalance in phages and bacteria in the intestinal tract can cause diseases. This review elucidates interactions between phages and bacteria in the human intestinal tract and their roles in the pathogenesis and treatment of diseases. Understanding the relationship among phages, bacteria and host diseases is conducive to promoting the application of phages in the treatment of human diseases. List of abbreviations EMBL-EBI The European Bioinformatics Institute; E. coli Escherichia coli; E. faecalis Enterobacter faecalis; B. fragilis Bacteroides fragilis; B. vulgatus Bacteroides vulgatus; SaPIs Staphylococcus aureus pathogenicity islands; ARGs Antibiotic resistance genes; STEC Shiga toxigenic E. coli; Stx Shiga toxin; BLAST Basic Local Alignment Search Tool; TSST-1 Toxic shock toxin 1; RBPs Receptor-binding proteins; LPS lipopolysaccharide; OMVs Outer membrane vesicles; PT Phosphorothioate; BREX Bacteriophage exclusion; OCR Overcome classical restriction; Pgl Phage growth limitation; DISARM Defense island system associated with restrictionmodification; R-M system Restriction-modification system; BREX system Bacteriophage exclusion system; CRISPR Clustered regularly interspaced short palindromic repeats; Cas CRISPR-associated; PAMs Prospacer adjacent motifs; crRNA CRISPR RNA; SIE; OMPs; Superinfection exclusion; Outer membrane proteins; Abi Abortive infection; TA Toxin-antitoxin; TLR Toll-like receptor; APCs Antigen-presenting cells; DSS Dextran sulfate sodium; IELs Intraepithelial lymphocytes; FMT Fecal microbiota transfer; IFN-γ Interferon-gamma; IBD Inflammatory bowel disease; AgNPs Silver nanoparticles; MDSC Myeloid-derived suppressor cell; CRC Colorectal cancer; VLPs Virus-like particles; TMP Tape measure protein; PSMB4 Proteasome subunit beta type-4; ALD Alcohol-related liver disease; GVHD Graft-versus-host disease; ROS Reactive oxygen species; RA Rheumatoid arthritis; CCP Cyclic citrullinated protein; AMGs Accessory metabolic genes; T1DM Type 1 diabetes mellitus; T2DM Type 2 diabetes mellitus; SCFAs Short-chain fatty acids; GLP-1 Glucagon-like peptide-1; A. baumannii Acinetobacter baumannii; CpG Deoxycytidylinate-phosphodeoxyguanosine; PEG Polyethylene glycol; MetS Metabolic syndrome; OprM Outer membrane porin M.
Association between the interferon‐γ +874 T/A polymorphism and susceptibility to systemic lupus erythematosus and rheumatoid arthritis: A meta‐analysis

We aimed to determine whether the interferon (IFN)‐γ +874 T/A polymorphism (rs2430561) is associated with susceptibility to systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). A meta‐analysis was conducted to assess the association between the IFN‐γ +874 T/A polymorphism and SLE or RA using allele contrast, homozygous contrast, recessive, and dominant models. A total of nine studies (six on SLE and three on RA), involving 1839 patients and 2272 controls, were included in the meta‐analysis. The meta‐analysis revealed a significant association between SLE and the TT genotype of the IFN‐γ +874 T/A polymorphism (odds ratio [OR] = 0.751, 95% confidence interval [CI] = 0.634–0.899, p = .001), and stratification by ethnicity indicated an association between the IFN‐γ +874 TT genotype and the Asian population. The analysis also revealed a significant association between SLE and the TT + TA genotype of the IFN‐γ +874 T/A polymorphism in Arab populations (OR = 1.598, 95% CI = 1.053–2.425, p = .028). However, no association between the IFN‐γ +874 T/A polymorphism and RA was found using allele contrast, recessive, dominant or homozygous contrast models in all study subjects and ethnic groups. This meta‐analysis demonstrated that the IFN‐γ +874 T/A polymorphism is associated with susceptibility to SLE in Asian and Arab populations.