Miracle-dz/UniFAR-FTUs huggingface dataset:
Whole-genome sequence analyses of Glaesserella parasuis isolates reveals extensive genomic variation and diverse antibiotic resistance determinants

Background Glaesserella parasuis (G. parasuis) is a respiratory pathogen of swine and the etiological agent of Glässer’s disease. The structural organization of genetic information, antibiotic resistance genes, potential pathogenicity, and evolutionary relationships among global G. parasuis strains remain unclear. The aim of this study was to better understand patterns of genetic variation, antibiotic resistance factors, and virulence mechanisms of this pathogen. Methods The whole-genome sequence of a ST328 isolate from diseased swine in China was determined using Pacbio RS II and Illumina MiSeq platforms and compared with 54 isolates from China sequenced in this study and 39 strains from China and eigtht other countries sequenced by previously. Patterns of genetic variation, antibiotic resistance, and virulence mechanisms were investigated in relation to the phylogeny of the isolates. Electrotransformation experiments were performed to confirm the ability of pYL1—a plasmid observed in ST328—to confer antibiotic resistance. Results The ST328 genome contained a novel Tn6678 transposon harbouring a unique resistance determinant. It also contained a small broad-host-range plasmid pYL1 carrying aac(6’)-Ie-aph(2”)-Ia and blaROB-1; when transferred to Staphylococcus aureus RN4220 by electroporation, this plasmid was highly stable under kanamycin selection. Most (85.13–91.74%) of the genetic variation between G. parasuis isolates was observed in the accessory genomes. Phylogenetic analysis revealed two major subgroups distinguished by country of origin, serotype, and multilocus sequence type (MLST). Novel virulence factors (gigP, malQ, and gmhA) and drug resistance genes (norA, bacA, ksgA, and bcr) in G. parasuis were identified. Resistance determinants (sul2, aph(3”)-Ib, norA, bacA, ksgA, and bcr) were widespread across isolates, regardless of serovar, isolation source, or geographical location. Conclusions Our comparative genomic analysis of worldwide G. parasuis isolates provides valuable insight into the emergence and transmission of G. parasuis in the swine industry. The result suggests the importance of transposon-related and/or plasmid-related gene variations in the evolution of G. parasuis.
El Niño and dry season rainfall influence hostplant phenology and an annual butterfly migration from Neotropical wet to dry forests

We censused butterflies flying across the Panama Canal at Barro Colorado Island (BCI) for 16 years and butterfly hostplants for 8 years to address the question: What environmental factors influence the timing and magnitude of migrating Aphrissa statira butterflies? The peak migration date was earlier when the wet season began earlier and when soil moisture content in the dry season preceding the migration was higher. The peak migration date was also positively associated with peak leaf flushing of one hostplant (Callichlamys latifolia) but not another (Xylophragma seemannianum). The quantity of migrants was correlated with the El Niño Southern Oscillation, which influenced April soil moisture on BCI and total rainfall in the dry season. Both hostplant species responded to El Niño with greater leaf flushing, and the number of adults deriving from or laying eggs on those new leaves was greatest during El Niño years. The year 1993 was exceptional in that the number of butterflies migrating was lower than predicted by the El Niño event, yet the dry season was unusually wet for an El Niño year as well. Thus, dry season rainfall appears to be a primary driver of larval food production and population outbreaks for A. statira. Understanding how global climate cycles and local weather influence tropical insect migrations improves the predictability of ecological effects of climate change.
Plasmid Profiling and Occurrence of β-Lactamase Enzymes in Multidrug-Resistant Uropathogenic Escherichia coli in Kathmandu, Nepal

Introduction Extended-spectrum β-lactamases (ESBL) among Gram-negative bacteria, predominantly Escherichia coli (E. coli), in Nepal, have been rising. The main objectives of this study were to determine the prevalence of uropathogenic E. coli, antibiotic resistance, ESBLs, ABLs (AmpC type β-lactamases), MBLs (metallo-β-lactamases) and KPCs (Klebsiella pneumoniae carbapenemases) and their correlation with plasmid profiling patterns among patients with urinary tract infections in a tertiary hospital in Kathmandu, Nepal. Methods The mid-stream urine samples collected from patients were inoculated in cystine–lactose–electrolyte-deficient (CLED) agar plates. E. coli producing ESBLs, ABLs, MBLs/KPC were identified phenotypically using standard microbiological methods. Plasmids were extracted by alkaline lysis method from E. coli isolates and profiled using agarose gel electrophoresis. Results Out of the total 2661 urine samples, E. coli were isolated in 64.34% (507/788), among which 170 (33.53%) were multidrug-resistant (MDR) isolates. All MDR isolates were resistant to amoxicillin and third-generation cephalosporins but were highly sensitive to imipenem (94.12%, 160/170), amikacin (92.94%, 158/170) and nitrofurantoin (86.47%, 147/170). Among 170 MDR isolates, 78.2% (133/170) were ESBLs, 46.3% (50/170) were AmpC, 11.2% (19/170) were MBL and 0.6% (1/170) were KPC producers. Coproduction of β-lactamases was detected in 24.12% (41/170) of isolates. E. coli isolates showed one plasmid (>33.5 kb), which was present in all the isolates. Overall, 44 different plasmid profile groups were identified based on molecular weight and number of plasmids. β-Lactamase producers were relatively resistant to the higher number of antibiotics tested (≤10) than non-producers (≤8), and the number of plasmids were higher in β-lactamase producers (≤7) than those in non-producers (≤5). Conclusion The higher prevalence of the ESBLs, AmpCs, KPCs and MBLs along with their coproduction in E. coli isolates highlights the importance of routine surveillance of ESBLs, AmpCs, KPCs and MBLs in microbiology laboratories using various phenotypic methods.
MultiCenter Interrupted Time Series Analysis: Incorporating Within and Between-Center Heterogeneity

Background Segmented regression (SR) is the most common statistical method used in the analysis of interrupted time series (ITS) data. However, this modeling strategy is indicated to produce spurious results when applied to aggregated data. For multicenter ITS studies, data at a given time point are often aggregated across different participants and settings; thus, conventional segmented regression analysis may not be an optimal approach. Our objective is to provide a robust method for analysis of ITS data, while accounting for two sources of heterogeneity, between participants and across sites. Methods We present a methodological framework within the segmented regression modeling strategy, where we introduced weights to account for between-participant variation and the differences across multiple sites. We empirically compared the proposed weighted segmented regression (wSR) with the conventional SR as well as with a previously published pooled analysis method using data from the Mobility of Vulnerable Elders in Ontario (MOVE-ON) project, a multisite ITS study. Results Overall, the wSR produced the most precise estimates, where they had the narrowest 95% CI, while the conventional SR method resulted in the least precise estimates. Our method also resulted in increased power. The pooled analysis method and the wSR had comparable results when there were ≤4 sites included in the overall analysis and when there was moderate to high between-site heterogeneity as measured by the I2 statistic. Conclusion Incorporating participant-level and site-level variability led to estimates that were more precise and accurate in determining the magnitude of the effect of an intervention and led to increased statistical power. This underscores the importance of accounting for the inherent variability in aggregated data. Extensive simulations are required to further assess the methods in a wide range of scenarios and outcome types.
A Systematic Review of Vancomycin Dosing in Patients with Hematologic Malignancies or Neutropenia

Objective To provide a comprehensive review of vancomycin dosing in patients with hematologic malignancies or neutropenia. Methods PubMed, Embase and the Cochrane Library were searched through April 2, 2020. Original studies relevant to vancomycin dosing regimen in adults with hematologic malignancies or neutropenia were included. No restriction was applied in study design and language. A descriptive analysis was performed. Results Twenty-three studies were included eventually, of which eighteen were case series studies, four were cohort studies and another one was a randomized controlled trial. Five case series studies made a clinical audit of conventional vancomycin dosing in patients with malignancies or neutropenia, showing that the proportion of patients with sub-therapeutic trough levels remained high, ranging from 32% to 88%. Seven case series studies and four cohort studies demonstrated that vancomycin clearance (CLva) tended to be higher in patients with hematologic malignancies or neutropenia, whereas volume of distribution (V) seemed to be comparable to the control group. Five studies proposed individualized initial dosing regimen per the pharmacokinetic changes; however, no prospective validation has been conducted in clinical setting. Additionally, four case series studies suggested that the correlation between vancomycin clearance and estimated creatinine clearance was relatively poor, bringing a great challenge to proper dosing strategy. A randomized controlled trial stated that therapeutic drug monitoring (TDM) of vancomycin could decrease the incidence of nephrotoxicity in immunocompromised febrile patients with hematologic malignancies. Conclusion The available evidence indicates that conventional vancomycin dosing leads to suboptimal concentration in patients with hematologic malignancy or neutropenia. TDM accompanied by pharmacokinetic interpretation can decrease the risk of nephrotoxicity. The individualization of the initial dosing regimen and mechanisms of augmented clearance require further research.
Spent females of deepwater squid Galiteuthis glacialis under the ice at the surface of the Weddell Sea (Antarctic)

Two large (dorsal mantle length 42.5 and 47.5 cm), mated spent females of circum-Antarctic bathypelagic cranchiid squid Galiteuthis glacialis were caught early in March 1992 at the surface of the ice hole in the western Weddell Sea over depths 1915-1920 m by the team of the U.S.A. -Russian Ice Station Weddell-I. The structure of the reproductive system of adult females is described for the first time in detail. Both were gelatinous, devoid of tentacles, with empty or almost empty stomachs. The empty spermatangia (sperm reservoirs of spermatophores) 30-35 mm in length were distributed in the mantle tissues parallel to the mantle surface and to each other in the dorso-anterior part of the mantle: 13 in one female, parallel to the body axis, and 20 in the other, parallel (13) or perpendicular (7) to the body axis. In the latter case, they represented probably two mating events. The spermatangia lay nearer to the inner than the outer mantle side and opened by a round window on the inner side; the skin with chromatophores above them remained intact. The spermatozoa had one flagellum and rod-like heads, length 5.0-5.3 μm, width 1.2-1.5 μm. The most characteristic features are: a very simple type of blood vessel branching making each micro-gonad currant-like, not grape-like; a very compact disposition of oviducal, nidamental glands and gill, forming a united complex located on both sides of the mantle cavity; and an ovary connected by mesentery along all its length with the continuation of the stomach from the caecum to the end of the gastrogenital ligament. Only immature degenerating trophoplasmatic oocytes, length 0.9-1.4, av. 1.0-1.2 mm, were contained in ovaries; only one mature egg (length 3.3 mm, width 2.4-2.5 mm) was found in each female. The absence of oocytes <0.9 mm and 1.5-3.2 mm indicates that the maturation of oocytes proceeds rather synchronously, one large portion of eggs (some tens of thousands) matures in a short time while others degenerate. The residual fecundity is assessed to be approximately 20,000 eggs. It is hypothesized that mating occurs shortly before spawning and that mature males do not undergo gelatinous degeneration and do not lose tentacles. Spermatophores are placed on the inner side of the female's mantle with the aid of the male's tentacles and/or arms (less probably by the penis), but the exact mode of implantation is unclear. Spawning probably occurs at depths of adult habitat (approx. 500–2500m), may be multiportional but short; the exhausted female loses neutral buoyancy, rises to the surface and dies. Rising to the surface after spawning is a common feature of females of many meso- and bathypelagic squids undergoing gelatinous degeneration during maturation (Onychoteuthidae, Gonatidae, Histio-teuthidae, Cranchiidae, etc.) and may explain the common occurrence of large deep-water squids in the stomachs of seabirds, including those incapable of diving, and marine mammals.
Multiple Factor Analysis of Depression and/or Anxiety in Patients with Acute Exacerbation Chronic Obstructive Pulmonary Disease

Objective To reveal the risk factors, the symptom distribution characteristics, the clinical values of white blood cell counts (WBC counts), red blood cell distribution width (RDW), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and monocyte-to-lymphocyte ratio (MLR) in hospitalized patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) combined with depression and/or anxiety. Methods The study included prospective cross-sectional and case–control studies, and was executed in the Affiliated Hospital of Zunyi Medical University, Guizhou, China. Previously diagnosed chronic obstructive pulmonary disease (COPD) patients who admitted to the hospital with AECOPD, patients with depression and/or anxiety, and healthy people were enrolled in the study. The Hamilton Rating Scales were used to assess all subjects, and the complete blood counts (CBC) were collected. Baseline data and clinical measurement data [spirometry, arterial blood gas analysis, and COPD evaluation test (the CAT scale)] from patients with AECOPD were collected. Results Of the 307 patients with AECOPD included, 63.5% (N=195) had depressive and/or anxiety symptoms, and 36.5% (N=112) had no symptoms. Sex, respiratory failure, number of comorbidities, number of acute exacerbations in the previous year and the CAT score were closely related to AECOPD combined with depression and/or anxiety (p<0.05). The CAT scale score were the independent risk factor (OR=6.576, 95% CI 3.812–11.342) and significant predictor of AECOPD with depression and/or anxiety (AUC=0.790,95% CI 0.740–0.834); the patients with depression and/or anxiety were more severe and characteristic than the patients with AECOPD combined with depression and/or anxiety; RDW was associated with AECOPD with depression and/or anxiety (p=0.020, OR1.212,95% CI1.03–1.426), and had certain clinical diagnostic value (AUC=0.570,95% CI 0.531–0.626). Conclusion Depression and anxiety should not be ignored in patients with AECOPD. The severity and quality of life of COPD were closely related to the occurrence of depression and/or anxiety symptoms. In most cases, perhaps depression and anxiety in AECOPD are only symptoms and not to the extents of the diseases. RDW had clinical diagnostic value in AECOPD combined with depression and/or anxiety. NLR, PLR, MLR, and RDW may become the novel indicators for evaluating the degree of inflammation of AECOPD and deserve further research.
Decreased Serum Retinoic Acid May Predict Poor Outcome in Ischemic Stroke Patients

Background and Aims Decreased serum retinoic acid (RA) levels have been shown to be linked with increased mortality in cardiovascular diseases. This study aimed to investigate the relationship between serum RA and 3-month functional outcome after ischemic stroke. Methods Between January 2019 and September 2019, we prospectively recruited ischemic stroke patients within 24 hrs of symptom onset. Serum RA levels were measured for all patients at admission. The primary outcome was defined as poor functional outcome (modified Rankin Scale 3–6) at 90 days. The secondary outcome was defined as early neurological deterioration (END), which is considered as an increase of ≥1 point in motor power or total National Institutes of Health Stroke Scale score of ≥2 points within 7 days. Results A total of 217 patients were included in the analysis. The median RA levels were 2.9 ng/mL. Ninety-four (43.3%) and 65 (30.0%) patients experienced 3-month poor outcome and END, respectively. After adjusted for potential confounders, decreased levels of serum RA were associated with a higher risk of poor outcome (P for trend = 0.001) and END (P for trend = 0.002). Adding RA quartile to the existing risk factors improved risk prediction for poor outcome [net reclassification improvement (NRI) = 42.6%, P = 0.001; integrated discrimination improvement (IDI) = 5.7%, P = 0.001] and END (NRI index = 45.4%, P = 0.001; IDI = 4.3%; P = 0.005). Conclusion Low serum RA levels at baseline were associated with poor prognosis at 90 days after ischemic stroke, suggesting that RA may be a potential prognostic biomarker for ischemic stroke.
CFTR Regulates the Proliferation, Migration and Invasion of Cervical Cancer Cells by Inhibiting the NF-κB Signalling Pathway

Background The cystic fibrosis transmembrane conductance regulator (CFTR) and nuclear factor κB (NF-κB) signalling pathways are currently regarded as co-regulators of the occurrence of cervical cancer. However, the detailed mechanism of CFTR- and NF-κB-mediated effects in cervical cancer remains to be elucidated. This study aimed to investigate the mechanism by which CFTR and NF-κB influence the development of cervical cancer. Patients and Methods CFTR ΔF508 mutation and CFTR promoter methylation were detected in cervical tissue samples. NF-κB p65 and IκBα protein levels were tested in HeLa cells with CFTR overexpression and knockdown by Western blotting. The effects of CFTR on cell proliferation, migration, and invasion were examined in HeLa cells by WST-1 and soft agar assays, cell wound scratch assay, and Matrigel invasion assays, respectively. The protein–protein interaction (PPI) network was constructed by using GeneMANIA. GeneCoDis3 was used to perform Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment analysis on genes in the PPI network. Results CFTR mutation and CFTR promoter methylation were not associated with the occurrence of cervical cancer. NF-κB p65 protein levels were decreased in CFTR overexpression lines and increased in CFTR knockdown lines, and IκBα levels were affected in the opposite manner, indicating that CFTR inhibited the NF-κB signalling pathway. CFTR also regulated the cell proliferation, migration, and invasion ability of cervical cancer cells. When CFTR was overexpressed, cell proliferation, migration, and invasion ability were decreased. There were 20 genes that interacted with CFTR. KEGG pathway analysis showed enrichment in the gastric acid secretion, chemokine signalling, bile secretion and apoptosis pathways. Conclusion CFTR plays an important role in cancer cell proliferation, migration and invasion by inhibiting the NF-κB signalling pathway in cervical cancer.
Characterization of Polyphenol Oxidase from Walnut

Theenzyme polyphenoloxidase (PPO)isnearly ubiquitousin KingdomPlantae andcatalyzes the oxidation of phenolic compounds into highly reactive quinones. Although the functional importance of PPO in plants remains uncertain, a putative antipathogen role for walnut (Juglans regia) PPO was posited as early as 1911. However, despite the rich diversity of phenolics present in walnut leaves and hulls, walnut PPO has been little studied since the early 1900s. We cloned a PPO-encoding gene from a walnut pistillate flower cDNA library and designated the gene jrPPO1. Genomic Southern analysis demonstrated that jrPPO1 is the sole PPO gene in walnut. Transgenic tobacco (Nicotiana tabacum) plants expressing jrPPO1 display greater than 10-fold increases in leaf PPO activity compared with wild- type tobacco, demonstrating that jrPPO1 encodes a functional enzyme. The jrPPO1 protein is expressed primarily in the leaves, hulls, and flowers of walnut trees and is not regulated by wounding or methyl jasmonate. To examine whether walnut PPO could affect pathogen resistance, tobacco plants expressing jrPPO1 were challenged with Pseudomonas syringae pv. tabaci. Based on both symptom development and quantitative analyses of bacterial growth in planta, the PPO-expressing plants did not display increased resistance to this pathogen. Leaf extract browning assays indicated that tobacco leaves lack the endogenous phenolic substrates required for significant jrPPO1 activity and quinone production in planta.
The Epidemiology of Migraine Headache in Arab Countries: A Systematic Review

Background Recurring migraine disorders are a common medical problem, standing among the top causes of disability and sufferings. This study aimed to evaluate epidemiological evidence to report updated estimates on prevalence, risk factors, and associated comorbidities of migraine headache in the Arab countries. Design and Setting. A systematic review was conducted at the College of Public Health and Health Informatics, Riyadh, Saudi Arabia. Methods A systematic search in electronic databases, such as PubMed and Embase, as well as manual searches with cross-referencing was performed from 1990 up to 2019. Overall, 23 included papers were rated independently by two reviewers. Studies were eligible for inclusion only if they investigated migraine headache epidemiology in any Arab country and were published in English. Results Migraine prevalence among the general population ranged between 2.6% and 32%. The estimated prevalence of migraine headache among medical university students ranged between 12.2% and 27.9% and between 7.1% and 13.7% in schoolchildren (6 to 18 years). Females were found more likely to have migraine than males. The duration of migraine attacks became shorter with increasing age, while chronic (daily) migraine showed increasing prevalence with age. The most commonly reported comorbidities with migraine included anxiety, hypertension, irritable bowel syndrome, and depression. Most common headache-triggering factors included stress, fatigue, sleep disturbances, prolonged exposure to excessive sunlight or heat, and hunger. Conclusion The prevalence and risk factors of migraine headache in Arab countries are comparable to reports from western countries. Longitudinal studies are still needed to investigate the prognosis and predictors of chronicity in the arab countries.