Miracle-dz/UniFAR-FTUs huggingface dataset:
Detection of Plasmid-Mediated Resistance to Metronidazole in Clostridioides difficile from River Water

The combination of direct plating and culture after enrichment was used in order to gain a spectrum of C. difficile ribotypes present in the water samples. Toxigenic C. difficile ribotypes detected in surface water and in wastewater treatment plants overlapped with those derived from patients with CDI and/or animals. Importantly, a recently discovered plasmid-mediated resistance to metronidazole, a drug used for the treatment of CDI, was detected in C. difficile from river water. ABSTRACT Clostridioides difficile is one of the most important human pathogens. The identification of its possible sources is important for the understanding of C. difficile infection (CDI) epidemiology. A total of 16 water samples from wastewater and surface water in South Moravia in the Czech Republic and 82 samples of fish and gulls were collected between May and July 2019. C. difficile isolates were cultured by direct plating and after enrichment on chromogenic media. Susceptibility testing to eight antimicrobials was performed by Etest. C. difficile isolates were characterized by ribotyping, multilocus sequence typing, multilocus tandem repeats analysis, and toxin gene detection. Samples from fish and gulls were C. difficile negative; a total of 15 C. difficile isolates from 8 out of 16 water samples were cultured (6 out of 14 surface water samples yielded 6 isolates, and 2 out of 2 wastewater samples yielded 9 isolates). Direct plating was culture positive in 6 out of 16 samples (12 isolates), and enrichment culture was positive in an additional 2 out of 16 samples (3 isolates). Twelve different ribotyping profiles and 14 sequence types of clades 1, 4, and 5 were identified. Five isolates did not carry genes for toxins, and eight isolates carried genes for toxins A and B; the remaining two isolates (RT078) carried the genes for toxins A, B, and binary. All C. difficile isolates were susceptible to amoxicillin, moxifloxacin, tetracycline, and vancomycin and resistant to ciprofloxacin. A high level of erythromycin resistance (>256 mg/L) was detected in eight isolates. Clindamycin resistance was found in 14 isolates, 6 of which showed a high level of resistance (>256 mg/L) and carried ermB. Surprisingly, one isolate (RT010, ST15) showed resistance to metronidazole (12 mg/L) with the presence of the plasmid pCD-METRO. In conclusion, a diverse spectrum of C. difficile strains was found in wastewater and surface water. A recently discovered plasmid-bound resistance to metronidazole was detected in C. difficile from the surface water sample. IMPORTANCE The combination of direct plating and culture after enrichment was used in order to gain a spectrum of C. difficile ribotypes present in the water samples. Toxigenic C. difficile ribotypes detected in surface water and in wastewater treatment plants overlapped with those derived from patients with CDI and/or animals. Importantly, a recently discovered plasmid-mediated resistance to metronidazole, a drug used for the treatment of CDI, was detected in C. difficile from river water.
The magnitude of parental stress is highly variable following pediatric concussion: using the transactional model of stress to understand parent experiences

ABSTRACT Objectives: To use the Transactional Model of Stress to understand variations in parental stress following pediatric concussion. Methods: Mixed-methods design. 49 children with concussion (13.8 ± 2.3 years, nfemales = 27) and their parent (nfemales = 40) were recruited from a specialty clinic. Quantitative data were collected via surveys at the child’s initial clinic visit. Qualitative data were collected through an eleven-question, semi-structured interview with 12 parents. Interview questions focused on post-concussion stressors and data were analyzed using thematic analysis. Multivariable linear regression analyzed predictors of parental stress . Results: Ten of the parents interviewed (83%) described the concussion as having a negative overall effect on their stress, while two parents described the overall experience as positive. Coping abilities and other life stressors were described as reasons for varying stress levels. Neurotic and conscientious personality factors and the child’s quality of life total score accounted for 45% of the variance in parental stress (R2 = 0.451, F(3,33) = 9.03, p < 0.001). Conclusions: Parental stress following pediatric concussion is highly variable. The Transactional Model of Stress appears useful to understand this phenomenon. Future studies should investigate interventions to reduce stress for parents experiencing high levels following their child’s concussion.
Resistance to obesity prevents obesity development without increasing spontaneous physical activity and not directly related to greater metabolic and oxidative capacity

There are evidence that obese-resistant animals are more physically active, due to a higher rate of lipid oxidation. Efficiency in such pathways can favor greater spontaneous physical activity and, consequently, less body fat deposition. The aim of study was characterizing the nutritional profile and spontaneous physical activity in the condition of Resistance to Obesity (OR). Wistar rats were randomized into standard diet (SD; n = 50) and high-fat diet (HFD; n = 50) groups, after obesity induction, were redistributed into Control (C), False-control (FC), Propensity to obesity (OP) and OR, and then spontaneous physical activity was evaluated. Analyzed parameters: body mass (BM), epididymal (EF), retroperitoneal (RF), visceral (VF) and respective summations (∑), adiposity index (AI), nutritional, morphological, biochemical and metabolic parameters and protein quantification. The comparison of the groups was performed by ANOVA one or two factors, with 5% significance adopted. OP and FC presented high final MC values compared to C and OR. OR had lower EF, RF, VF, ∑ and IA compared to OP. OR had similar values to C and higher HDL than FC and OP. In GTT, OR and C presented similar values and both were lower than OP in the 30 minutes. OP promoted higher values than C for glycemic AUC. OR had higher PPARγ content than C and OP, as well as levels similar to C for leptin and insulin. Spontaneous physical activity did not differ between groups. The results were not enough to show that OR animals have greater lipid oxidative capacity, as well as greater spontaneous physical activity.
The role of ex-situ perfusion for thoracic organs

Purpose of review Ex-situ machine perfusion for both heart (HTx) and lung transplantation (LuTx) reduces ischemia–reperfusion injury (IRI), allows for greater flexibility in geographical donor management, continuous monitoring, organ assessment for extended evaluation, and potential reconditioning of marginal organs. In this review, we will delineate the impact of machine perfusion, characterize novel opportunities, and outline potential challenges lying ahead to improve further implementation. Recent findings Due to the success of several randomized controlled trials (RCT), comparing cold storage to machine perfusion in HTx and LuTx, implementation and innovation continues. Indeed, it represents a promising interface for organ-specific therapies targeting IRI, allo-immune responses, and graft reconditioning. These mostly experimental efforts range from genetic approaches and nanotechnology to cellular therapies, involving mesenchymal stem cell application. Despite tremendous potential, prior to clinical transition, more data is needed. Summary Collectively, machine perfusion constitutes the vanguard in thoracic organ transplantation research with extensive potential for expanding the donor pool, enhancing transplant outcomes as well as developing novel therapy approaches.
Gene expression underlying parenting and being parented shows limited plasticity in response to different ambient temperatures

Flexible interactions between parents and offspring are essential for buffering families against variable, unpredictable, and challenging environmental conditions. In the subsocial carrion beetle, Nicrophorus orbicollis, mid‐summer temperatures impose steep fitness costs on parents and offspring but do not elicit behavioural plasticity in parents. Here, we ask if plasticity of gene expression underpins this behavioural stability or facilitates independent compensation by larvae. To test this, we characterized gene expression of parents and offspring before and during active parenting under benign (20°C) and stressful (24°C) temperatures to identify genes of parents and offspring associated with thermal response, parenting/being parented, and gene expression plasticity associated with behavioural stability of parental care. The main effects of thermal and social condition each shaped patterns of gene expression in females, males, and larvae. In addition, we implicated 79 genes in females as “buffering” parental behaviour across environments. The majority of these underwent significant changes in expression in actively parenting mothers at the benign temperature, but not at the stressful temperature. Our results suggest that neither genetic programmes for parenting nor their effects on offspring gene expression are fundamentally different under stressful conditions, and that behavioural stability is associated primarily with the maintenance of existing genetic programmes rather than replacement or supplementation. Thus, while selection for compensatory gene expression could expand the range of thermal conditions parents will tolerate, without expanding the toolkit of genes involved selection is unlikely to lead to adaptive changes of function.
Rhamnosyltransferases involved in the biosynthesis of flavone rutinosides in Chrysanthemum species

Abstract Linarin (acacetin-7-O-rutinoside), isorhoifolin (apigenin-7-O-rutinoside), and diosmin (diosmetin-7-O-rutinoside) are chemically and structurally similar flavone rutinoside (FR) compounds found in Chrysanthemum L. (Anthemideae, Asteraceae) plants. However, their biosynthetic pathways remain largely unknown. In this study, we cloned and compared FRs and genes encoding rhamnosyltransferases (RhaTs) among eight accessions of Chrysanthemum polyploids. We also biochemically characterized RhaTs of Chrysanthemum plants and Citrus (Citrus sinensis and Citrus maxima). RhaTs from these two genera are substrate-promiscuous enzymes catalyzing the rhamnosylation of flavones, flavanones, and flavonols. Substrate specificity analysis revealed that Chrysanthemum 1,6RhaTs preferred flavone glucosides (e.g. acacetin-7-O-glucoside), whereas Cs1,6RhaT preferred flavanone glucosides. The nonsynonymous substitutions of RhaTs found in some cytotypes of diploids resulted in the loss of catalytic function. Phylogenetic analysis and specialized pathways responsible for the biosynthesis of major flavonoids in Chrysanthemum and Citrus revealed that rhamnosylation activity might share a common evolutionary origin. Overexpression of RhaT in hairy roots resulted in 13-, 2-, and 5-fold increases in linarin, isorhoifolin, and diosmin contents, respectively, indicating that RhaT is mainly involved in the biosynthesis of linarin. Our findings not only suggest that the substrate promiscuity of RhaTs contributes to the diversity of FRs in Chrysanthemum species but also shed light on the evolution of flavone and flavanone rutinosides in distant taxa.
Methods to promote seed germination in the lacquer tree, Toxicodendron vernicifluum (Stokes) F.A. Barkley

The lacquer tree, Toxicodendron vernicifluum, is a common industrial crop in East Asia. However, T. vernicifluum seeds are extremely difficult to germinate, which poses a major obstacle to establishing seedlings for sap production. In this study, we examined the germination properties of T. vernicifluum seeds in order to establish an inexpensive and effective method to promote seed germination. The seeds are covered with a hard endocarp, which we degrade using conventional sulfuric acid-based methods. Although sulfuric acid was effective in promoting seed germination, the germination rate was less than 5%. In addition to treatment with sulfuric acid, co-treatment with cold temperatures or the phytohormone gibberellic acid increased the germination rate to 22–35%. Seed viability analysis combined with specific gravity-based seed selection revealed that more than half of the seeds housed embryos that were incapable of germination. In additions, specific gravity-based seed selection aided in the selection of seeds capable of germination and improved the germination rate to approximately 47%. Taken together, our results suggest that the low germination rate of T. vernicifluum seeds is due to deep seed dormancy—which is controlled by physical and physiological mechanisms—and low embryo viability. To improve the germination rate of T. vernicifluum seeds, we propose an effective method whereby seeds with good germination capacity are selected based on specific gravity, following which their physiological dormancy is inactivated through cold pretreatment.
Antibody Response in Immunocompromised Patients With Hematologic Cancers Who Received a 3-Dose mRNA-1273 Vaccination Schedule for COVID-19.

Importance It has become common practice to offer immunocompromised patients with hematologic cancers a third COVID-19 vaccination dose, but data substantiating this are scarce. Objective To assess whether a third mRNA-1273 vaccination is associated with increased neutralizing antibody concentrations in immunocompromised patients with hematologic cancers comparable to levels obtained in healthy individuals after the standard 2-dose mRNA-1273 vaccination schedule. Design, Setting, and Participants This prospective observational cohort study was conducted at 4 university hospitals in the Netherlands and included 584 evaluable patients spanning the spectrum of hematologic cancers and 44 randomly selected age-matched adults without malignant or immunodeficient comorbidities. Exposures One additional mRNA-1273 vaccination 5 months after completion of the standard 2-dose mRNA-1273 vaccination schedule. Main Outcomes and Measures Serum immunoglobulin G (IgG) antibodies to spike subunit 1 (S1) antigens prior to and 4 weeks after a third mRNA-1273 vaccination, and antibody neutralization capacity of wild-type, Delta, and Omicron variants in a subgroup of patients. Results In this cohort of 584 immunocompromised patients with hematologic cancers (mean [SD] age, 60 [11.2] years; 216 [37.0%] women), a third mRNA-1273 vaccination was associated with median S1-IgG concentrations comparable to concentrations obtained by healthy individuals after the 2-dose mRNA-1273 schedule. The rise in S1-IgG concentration after the third vaccination was most pronounced in patients with a recovering immune system, but potent responses were also observed in patients with persistent immunodeficiencies. Specifically, patients with myeloid cancers or multiple myeloma and recipients of autologous or allogeneic hematopoietic cell transplantation (HCT) reached median S1-IgG concentrations similar to those obtained by healthy individuals after a 2-dose schedule. Patients receiving or shortly after completing anti-CD20 therapy, CD19-directed chimeric antigen receptor T-cell therapy recipients, and patients with chronic lymphocytic leukemia receiving ibrutinib were less responsive or unresponsive to the third vaccination. In the 27 patients who received cell therapy between the second and third vaccination, S1 antibodies were preserved, but a third mRNA-1273 vaccination was not associated with significantly enhanced S1-IgG concentrations except for patients with multiple myeloma receiving autologous HCT. A third vaccination was associated with significantly improved neutralization capacity per antibody. Conclusions and Relevance Results of this cohort study support that the primary schedule for immunocompromised patients with hematologic cancers should be supplemented with a delayed third vaccination. Patients with B-cell lymphoma and allogeneic HCT recipients need to be revaccinated after treatment or transplantation. Trial Registration EudraCT Identifier: 2021-001072-41.
Relationships Among Parenting Stress and Well-Being, COVID-19 Information Management, and Children's COVID-19 Fear

ABSTRACT: Objective: During the COVID-19 pandemic, caregivers who are facing high stress levels and decreased emotional well-being may parent their children differently. Certain children are experiencing greater fear in response to COVID-19, and research is needed to identify parenting behaviors significantly linked with children's COVID-19 fear. The purpose of this article was to evaluate whether the association between parenting stress and children's COVID-19 fear could be explained by parents' COVID-19 information management and emotional well-being. Methods: Participants were recruited through Amazon Mechanical Turk. The sample consisted of 595 caregivers of children during the COVID-19 pandemic; 40.0% men, 69.2% non-Latinx White, 12.1% Black, 10.1% Latinx, 6.6% Asian, and <2% others. Children had an average age of 11.3 years. Parents completed self-report measures. Results: The bootstrapped confidence interval (0.040, 0.148) for the indirect effect (0.090) revealed that parent emotional well-being significantly mediated the relation between parenting stress and children's COVID-19 fear. In addition, parent management of children's COVID-19 knowledge significantly mediated the relation between parenting stress and children's COVID-19 fear. Conclusion: We found that the combined effect of parents' emotional well-being and parents' management of children's COVID-19 knowledge significantly mediated the positive relation between parenting stress and children's COVID-19 fear. Based on our findings, once parents' parenting stress is decreased and their well-being increases, parents may be more likely to provide children with developmentally appropriate and accurate COVID-19 information.
Greater hip abductor size in prearthritic patients with developmental dysplasia of the hip versus femoroacetabular impingement

Developmental dysplasia of the hip (DDH) and femoroacetabular impingement (FAI) are common hip pathologies and important risk factors for osteoarthritis, yet the disease mechanisms differ. DDH involves deficient femoral head coverage and a shortened abductor moment arm, so this study hypothesized that the cross‐sectional area (CSA) of the gluteus medius/minimus muscle complex and the stabilizing iliocapsularis muscle would be larger in DDH versus FAI, without increased fatty infiltration. A longitudinal cohort identified prearthritic patients with DDH or FAI who underwent imaging before surgery. Patients with DDH and FAI (Cam, Pincer, or Mixed) were 1:1 matched based on age, sex, and body mass index. Magnetic resonance imaging was used to measure the gluteus medius/minimus complex and iliocapsularis in two transverse planes. Amira software was used to quantify muscle and noncontractile tissue. Paired samples t‐tests were performed to compare muscle size and composition (p < 0.05). There were no differences in the iliocapsularis muscle. Patients with DDH had significantly larger CSA of the gluteus medius/minimus complex at both transverse planes, and the noncontractile tissue proportion did not differ. The mean difference in overall muscle CSA at the anterior inferior iliac spine was 4.07 ± 7.4 cm2 (p = 0.005), with an average difference of 12.1%, and at the femoral head this was 2.40 ± 4.37 cm2 (p = 0.004), with an average difference of 20.2%. This study reports a larger CSA of the gluteus medius/minimus muscle complex in DDH compared to FAI, without a difference in noncontractile tissue, indicating increased healthy muscle in DDH.
A comparative study on roles of natural killer T cells in two diet-induced non-alcoholic steatohepatitis-related fibrosis in mice

Abstract Background Immune responses are important in the progression of non-alcoholic fatty liver disease (NAFLD). Natural killer T (NKT) cells are main components of the innate immune system that modulate immunity. However, the role of NKT cells in NAFLD remains controversial. Objective We aimed to investigate the role of NKT cells in non-alcoholic steatohepatitis (NASH)-related fibrosis in fast food diet (FFD)- and methionine choline-deficient (MCD) diet-induced mouse models. Methods Hepatic NKT cells were analysed in wild-type (WT) and CD1d-/- mice fed FFD or MCD diets. Hepatic pathology, cytokine profiles and liver fibrosis were evaluated. Furthermore, the effect of chronic administration of α-galactosylceramide (α-GalCer) on liver fibrosis was investigated in both FFD- and MCD-treated mice. Results FFD induced a significant depletion of hepatic NKT cells, thus leading to mild to moderate NASH and early-stage fibrosis, while mice fed MCD diets developed severe liver inflammation and progressive fibrosis without a significant change in hepatic NKT cell abundance. FFD induced a similar liver fibrogenic response in CD1d-/- and WT mice, while MCD induced a higher hepatic mRNA expression of Col1α1 and TIMP1 as well as relative fibrosis density in CD1d-/- mice than WT mice (31.8 vs. 16.3, p = .039; 40.0 vs. 22.6, p = .019; 2.24 vs. 1.59, p = .036). Chronic administration of α-GalCer induced a higher hepatic mRNA expression of TIMP1 in MCD-treated mice than controls (36.7 vs. 14.9, p = .005). Conclusion NKT cells have protective roles in NAFLD as the disease progresses. During diet-induced steatosis, mild to moderate NASH and the early stage of fibrosis, hepatic NKT cells are relatively depleted, leading to a proinflammatory status. In severe NASH and the advanced stage of liver fibrosis, NKT cells play a role in inhibiting the NASH-related fibrogenic response. Chronic administration of α-GalCer induces NKT cell anergy and tolerance, which may play a role in promoting the liver fibrogenic response.
D-Dimer as a Sensitive Biomarker of Survival Rate in Patients with COVID-19

Objective: The global case fatality rate of coronavirus disease 2019 is 2.16% as announced by the World Health Organization. In Indonesia, according to the Ministry of Health, the number is even higher, reaching a 2.8% case fatality rate. D-dimer levels were found to affect coronavirus disease 2019 patient’s survival in several studies. The study aimed to determine whether the amount of D-dimer predicted survival in coronavirus disease 2019 patients. Materials and Methods: This research was performed in a retrospective cohort design and used survival analysis. From March 1, 2020, to August 31, 2020, the samples were collected from polymerase chain reaction-confirmed coronavirus disease 2019 patients at Mohammad Hoesin General Hospital in Palembang, South Sumatera, Indonesia. We used electronic medical records to obtain demographic (age and gender), coexisting condition, laboratory (coagulation and hematologic test), and outcome (non-survivors or survivors) data. The chi-square and Mann–Whitney tests were used to evaluate the results. The Kaplan–Meier method and the Mantel–Haenszel log-rank test were used to examine D-dimer levels and patient outcomes. Youden index was calculated to determine the optimal cut-off value of D-dimer. Results: There were 52 non-survivors and 235 survivors among the 287 patients who met the inclusion criterion. Non-survivors had D-dimer levels of more than 1.49 mg/L in 82.69% of cases. Males had lower cut-off compared to females (>1.49 mg/L vs. >2.2 mg/L). The researchers discovered a highly significant correlation between D-dimer levels and coronavirus disease 2019 mortality (P = .001). The c-index analysis showed that D-dimer (0.79, 95% CI: 0.73-0.83) ability for mortality prediction was the second-best compared with other laboratory markers. Conclusion: D-dimer can be used as a predictor of coronavirus disease 2019 in-hospital mortality for early identification of coagulopathy.