Miracle-dz/UniFAR-FTUs huggingface dataset:
Combination of Cystatins 9 and C Modulates Serum Biomarkers Associated with Inflammation and Provides Prophylactic as Well as Long-Term Protection against Multidrug-Resistant Klebsiella pneumoniae

We have identified recombinant human cystatins 9 (rCST9) and C (rCSTC) as a combination immunotherapeutic treatment against multidrug-resistant (MDR) New Delhi metallo-β-lactamase-1 (NDM-1)-producing Klebsiella pneumoniae. We evaluated the lasting protection of rCST9/rCSTC treatment against MDR NDM-1 K. pneumoniae pneumonia. ABSTRACT We have identified recombinant human cystatins 9 (rCST9) and C (rCSTC) as a combination immunotherapeutic treatment against multidrug-resistant (MDR) New Delhi metallo-β-lactamase-1 (NDM-1)-producing Klebsiella pneumoniae. We evaluated the lasting protection of rCST9/rCSTC treatment against MDR NDM-1 K. pneumoniae pneumonia. Results showed that rCST9/rCSTC treatment modulated endogenous serum biomarkers, cystatins 9 and C and amyloid A, associated with poor patient outcomes and provided prophylactic and long-term protection in a murine model of pneumonia.
Evaluation of sperm DNA fragmentation using multiple methods: a comparison of their predictive power for male infertility

Objective The usual seminal profile has been customarily used for diagnosing male infertility based on an examination of semen samples. However, sperm DNA fragmentation has also been causally linked to reproductive failure, suggesting that it should be evaluated as part of male infertility assessments. To compare the ability of the five most widely utilized methodologies of measuring DNA fragmentation to predict male infertility and reactive oxygen species by Oxisperm kit assay. Methods In this case-control study, which received ethical committee approval, the participants were divided into fertile and infertile groups (50 patients in each group). Results The alkaline comet test showed the best ability to predict male infertility, followed by the terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) assay, the sperm chromatin dispersion (SCD) test, and the sperm chromatin structure assay (SCSA), while the neutral comet test had no predictive power. For our patient population, the projected cut-off point for the DNA fragmentation index was 22.08% using the TUNEL assay, 19.90% using SCSA, 24.74% using the SCD test, 48.47% using the alkaline comet test, and 36.37% using the neutral comet test. Significant correlations were found between the results of the SCD test and those obtained using SCSA and TUNEL (r =0.70 and r =0.68, respectively; p<0.001), and a statistically significant correlation was also found between the results of SCSA and the TUNEL assay (r =0.77, p<0.001). Likewise, the results of the alkaline comet test showed significant correlations with those of the SCD, SCSA, and TUNEL tests (r =0.59, r =0.57, and r =0.72, respectively; p<0.001). Conclusion The TUNEL assay, SCSA, SCD, and the alkaline comet test were effective for distinguishing between fertile and infertile patients, and the alkaline comet test was the best predictor of male infertility.
Cellular responses to ionizing radiation change quickly over time during early development in zebrafish

Animal cells constantly receive information about and respond to environmental factors, including ionizing radiation. Although it is crucial for a cell to repair radiation‐induced DNA damage to ensure survival, cellular responses to radiation exposure during early embryonic development remain unclear. In this study, we analyzed the effects of ionizing radiation in zebrafish embryos and found that radiation‐induced γH2AX foci formation and cell cycle arrest did not occur until the gastrula stage, despite the presence of major DNA repair‐related gene transcripts, passed on as maternal factors. Interestingly, P21/WAF1 accumulation began ∼6 h post‐fertilization, although p21 mRNA was upregulated by irradiation at 2 or 4 h post‐fertilization. These results suggest that the cellular responses of zebrafish embryos at 2 or 4 h post‐fertilization to radiation failed to overcome P21 protein accumulation and further signaling. Regulation of P21/WAF1 protein stabilization appears to be a key factor in the response to genotoxins during early embryogenesis.
Grazing Away the Resilience of Patterned Ecosystems

Ecosystems’ responses to changing environmental conditions can be modulated by spatial self-organization. A prominent example of this can be found in drylands, where formation of vegetation patterns attenuates the magnitude of degradation events in response to decreasing rainfall. In model studies, the pattern wavelength responds to changing conditions, which is reflected by a rather gradual decline in biomass in response to decreasing rainfall. Although these models are spatially explicit, they have adopted a mean-field approach to grazing. By taking into account spatial variability when modeling grazing, we find that (over)grazing can lead to a dramatic shift in biomass, so that degradation occurs at rainfall rates that would otherwise still maintain a relatively productive ecosystem. Moreover, grazing increases the resilience of degraded ecosystem states. Consequently, restoration of degraded ecosystems could benefit from the introduction of temporary small-scale exclosures to escape from the basin of attraction of degraded states.
Cognitive effects of video games in older adults and their moderators: a systematic review with meta-analysis and meta-regression

Abstract The growing interest in preserving cognition through video games in the ageing population is evidenced by its wealth of literature. However, there has been a lack of consensus on video games efficacy and even limited understanding on the factors moderating its effectiveness. The present review sought to evaluate video game effects, relative to no-game control condition, on cognitive functions in older adults. The functions included processing speed, attention, delayed memory, reasoning, and executive functions (inhibition, shifting and updating memory). Personal and methodological moderators were explored to explain the variability in cognitive effects using meta-regression. Through a systematic literature search of online databases, 27 intervention studies were eligible, with a total of 1126 participants, for analysis. Using random-effect models, small but significant training effects were found on updating memory but none were detected in other cognitive functions. The heterogeneity across studies was in general high for all cognitive functions and was partially accounted for, in all cognitive functions except for inhibition and updating, by different moderators such as the proportion of females, outcome measure parameters, training intensity, and game type. The findings highlight limited effects of video games on cognitive functions that were largely influenced by factors related to study design.
A high‐throughput and rapid method for accurate identification of emerging multidrug‐resistant Candida auris

Candida auris is an emerging multidrug‐resistant yeast associated with invasive infection in healthcare settings. Recently, C auris cases in the United States have been detected in 11 states with the majority of cases in New York, New Jersey and Illinois. Rapid and accurate identification of C auris is critical for patient care and the implementation of public health measures to control the spread of infection. Our aim was to develop and validate a rapid DNA extraction method using the Roche MagNA Pure 96 instrument and a TaqMan real‐time PCR assay for reliable, high‐throughput identification of C auris. We evaluated 247 patient dermal swab samples previously analysed by culture/MALDI‐TOF. The diagnostic sensitivity and specificity were 93.6% and 97.2%, respectively. The assay was highly reproducible with a detection limit of 1 C auris CFU/10 μL. A receiver operating characteristic curve analysis of the real‐time PCR data showed an area of 0.982 under the curve, with a CT cut‐off value of ≤37.0. The turnaround time from DNA extraction to real‐time PCR results was approximately 200 samples/day. In conclusion, we successfully validated a rapid and high‐throughput method for accurate and reproducible identification of C auris with a significantly reduced turnaround time compared to culture/MALDI‐TOF based methods.
The prevelance of mesiodens in a group of non-syndromic Turkish children: a radiographic study.

Purpose The aim of the present study is to determine the prevelance and clinical status of mesiodens in a group of non-syndromic Turkish children, with an analysis of the associated clinical-eruptive complications. Materials and Methods This study sample consists of 58142 pediatric patients'. Standard equipment and films were used in the suspected patients. The examination of all radiographs was performed under standard conditions by two pediatric dentists with over 10 years experience. Age, gender, number of mesiodens, morphology and clinical status were recorded in forms. Results A total of 83 mesiodentes were diagnosed in 59 children with ages ranging from 6-14 years. The prevelance of mesiodens was estimated as 0.1%. Males were more frequently affected than females in the ratio of 2.3:1. Of the 83 mesiodentes, 48.2% were conical, 31.3% were tuberculate and 20.5% were incisor like, 22.9% were inverted, and 68.7% were fully impacted. The number of mesiodens was one in 36 cases (61.0%), two in 22 cases (37.3%) and three in one case (1.7%). The mean age at the time of diagnosis of the mesiodens was 9.5 years. The main complication associated with the mesiodens was displacement or rotation of the permanent teeth (73.3%). Conclusion This study presents 0.1% prevelance of mesiodens in a group of Turkish children sample. The majority of the mesiodentes were unilateral located in the premaxillary region, were conical shaped, and remained unerupted. The mean age at the time of diagnosis of the mesiodens in this study was 9.5 years, with this period being later than the eruption time of the maxillary central incisor.
A comparative analysis of clinicopathological factors between esophageal small cell and basaloid squamous cell carcinoma

Abstract Esophageal small cell carcinoma (E-SmCC) and basaloid squamous cell carcinomas (BSCCs) are both highly aggressive malignancies, but their detailed differences in clinical behaviors have remained virtually unknown. In addition, treatment strategies of the patients with E-SmCC have not been established. 29 cases of E-SmCC and 39 with BSCC were examined in this study to clarify the clinical features and outcome of the patients with E-SmCC and to compare the findings with those of BSCC. E-SmCCs presented a more advanced status than BSCC (TNM Stage: P = .002). Esophagectomy was performed in 15 small cell carcinoma patients and 14 were treated with non-surgical/systemic therapy. The clinical outcome of the small cell carcinoma cases was significantly worse than those with BSCC (P = .001), but results of a stage-stratified analysis revealed that the Stage I small cell carcinoma patients presented favorable prognosis (3-year survival rate 100%, n = 4). In contrast, among those with Stage II–IV, clinical outcome tended to be better in the systemic therapy group (3-year survival rate 49%, n = 13) than the surgically treated group (3-year survival rate 0%, n = 12). E-SmCC was a more aggressive neoplasm than BSCC. However, early detection could possibly improve the clinical outcome of patients with E-SmCC. Systemic therapy could also benefit the patients with advanced disease (Stage II–IV).
Blood-Derived DNA Methylation Signatures of Crohn's Disease and Severity of Intestinal Inflammation.

BACKGROUND & AIMS Crohn's disease is a relapsing and remitting inflammatory disorder with a variable clinical course. Although most patients present with an inflammatory phenotype (B1), approximately 20% of patients rapidly progress to complicated disease, which includes stricturing (B2), within 5 years. We analyzed DNA methylation patterns in blood samples of pediatric patients with Crohn's disease at diagnosis and later time points to identify changes that associate with and might contribute to disease development and progression. METHODS We obtained blood samples from 164 pediatric patients (1-17 years old) with Crohn's disease (B1 or B2) who participated in a North American study and were followed for 5 years. Participants without intestinal inflammation or symptoms served as controls (n = 74). DNA methylation patterns were analyzed in samples collected at time of diagnosis and 1-3 years later at approximately 850,000 sites. We used genetic association and the concept of Mendelian randomization to identify changes in DNA methylation patterns that might contribute to the development of or result from Crohn's disease. RESULTS We identified 1189 5'-cytosine-phosphate-guanosine-3' (CpG) sites that were differentially methylated between patients with Crohn's disease (at diagnosis) and controls. Methylation changes at these sites correlated with plasma levels of C-reactive protein. A comparison of methylation profiles of DNA collected at diagnosis of Crohn's disease vs during the follow-up period showed that, during treatment, alterations identified in methylation profiles at the time of diagnosis of Crohn's disease more closely resembled patterns observed in controls, irrespective of disease progression to B2. We identified methylation changes at 3 CpG sites that might contribute to the development of Crohn's disease. Most CpG methylation changes associated with Crohn's disease disappeared with treatment of inflammation and might be a result of Crohn's disease. CONCLUSIONS Methylation patterns observed in blood samples from patients with Crohn's disease accompany acute inflammation; with treatment, these change to resemble methylation patterns observed in patients without intestinal inflammation. These findings indicate that Crohn's disease-associated patterns of DNA methylation observed in blood samples are a result of the inflammatory features of the disease and are less likely to contribute to disease development or progression.
Perception of Environmental Risks and Behavioral Changes during Pregnancy: A Cross-Sectional Study of French Postpartum Women

Limiting exposure to environmental hazards during preconception and pregnancy is essential for preventing adverse pregnancy outcomes or developmental defects in offspring. However, the perception of environmental risk and the behavioral changes of women planning or having a pregnancy have rarely been investigated, except for a few risk factors. We thus performed a cross-sectional study of French postpartum women hospitalized in the Bordeaux University Hospital in 2017 by proposing a self-administrated survey. The main objective was to assess their level of awareness concerning a large panel of environmental hazards and modifications in their behavior during pregnancy in occupational and household environments. Among the 121 respondents, most identified the environment as a major factor for a healthy pregnancy but recognized a lack of knowledge regarding environmental risk factors. The internet, television, and magazines were their main sources of information. Most women modified some of their practices at work or home. These measures were rarely implemented in consultation with a health practitioner, which raises concerns about the relevance of the adjustments made. Our findings highlight the need to improve the quality of information available to women and to help them implement preventive measures in consultation with physicians.
PGC1A regulates the IRS1:IRS2 ratio during fasting to influence hepatic metabolism downstream of insulin

Significance The liver plays crucial roles in the control of glucose homeostasis during the fast-feeding cycle. It responds to insulin and glucagon to either store or provide glucose to other organs. Insulin resistance is a hallmark of metabolic diseases such as type 2 diabetes and nonalcoholic fatty liver disease. Associations have been made between low hepatic levels of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1A) and hepatic insulin resistance, but underlying mechanisms are elusive. We show that PGC1A controls the hepatic ratio of Insulin Receptor Substrates 1 (IRS1) and IRS2 expression, crucial for defining the precise insulin signal in hepatocytes to respond to fasting and feeding. Importantly, PGC1A is key for insulin-mediated suppression of hepatic glucose production. Precise modulation of hepatic glucose metabolism is crucial during the fasting and feeding cycle and is controlled by the actions of circulating insulin and glucagon. The insulin-signaling pathway requires insulin receptor substrate 1 (IRS1) and IRS2, which are found to be dysregulated in diabetes and obesity. The peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1A) is a fasting-induced transcriptional coactivator. In nonalcoholic fatty liver disease and in patients with type 2 diabetes, low hepatic PGC1A levels are associated with insulin resistance. However, how PGC1A activity impacts the hepatic insulin-signaling pathway is still unclear. We used gain- and loss-of-function models in mouse primary hepatocytes and measured hepatocyte insulin response by gene and protein expression and ex vivo glucose production. We found that the PGC1A level determines the relative ratio of IRS1 and IRS2 in hepatocytes, impacting insulin receptor signaling via protein kinase B/AKT (AKT). PGC1A drove the expression of IRS2 downstream of glucagon signaling while simultaneously reducing IRS1 expression. We illustrate that glucagon- or PGC1A-induced IRS2 expression was dependent on cAMP Response Element Binding Protein activity and that this was essential for suppression of hepatocyte gluconeogenesis in response to insulin in vitro. We also show that increased hepatic PGC1A improves glucose homeostasis in vivo, revealing a counterregulatory role for PGC1A in repressing uncontrolled glucose production in response to insulin signaling. These data highlight a mechanism by which PGC1A plays dual roles in the control of gluconeogenesis during the fasting-to-fed transition through regulated balance between IRS1 and IRS2 expression.
Vitamin K1 Supplementation Did Not Alter Inflammatory Markers and Clinical Status in Patients with Rheumatoid Arthritis.

BACKGROUND Rheumatoid arthritis (RA) is an inflammatory disorder in which the disease severity might be decreased by anti-inflammatory agents. There are several lines of evidence which support anti-inflammatory effects of vitamin K. The aim of this study was to examine whether vitamin K is a useful strategy for reducing inflammation in RA subjects. MATERIALS AND METHODS In this double-blind placebo controlled trial, 58 patients with definitive RA were randomly allocated into two groups to receive vitamin K1 as phylloquinone [10 mg/day] or placebo pills for 8 weeks. Clinical status using disease activity score-28 (DAS-28) and serum concentrations of some inflammatory markers (IL-6, hs-CRP, TNFα) were assessed at baseline and at the end of intervention. RESULTS There were no significant differences between the two groups regarding any of the baseline characteristics. In the vitamin K1 group, a 27 % decrease in serum levels of IL-6 (P = 0.006) and a 13 % decrease in DAS-28 (P = 0.041) were observed. However, after adjusting for relevant confounders, i. e. ; duration of RA, intake of folic acid supplements, energy intake, weight and baseline values of each variable, by comparing the two groups, we found no significant reduction in these markers. CONCLUSION Vitamin K1 supplementation at 10 mg/day for 8 weeks had no significant effects on blood biomarkers of inflammation and disease severity of patients with rheumatoid arthritis compared with the placebo group.
Paeonol inhibits the development of 1-chloro-2,4-dinitrobenzene-induced atopic dermatitis via mast and T cells in BALB/c mice

Our previous studies suggested that paeonol, the active constituent of the traditional Chinese medicine Cortex Moutan, may be an effective treatment for inflammatory disorders. In the present study, the therapeutic potential of paeonol on atopic dermatitis (AD) was investigated using animal and cell experiments. AD-like lesions were induced by repeated application of 1-chloro-2,4-dinitrobenzene (DNCB) to the shaved dorsal skin of BALB/c mice, and P815 cells were used for in vitro assays. The skin lesions, serum and spleens of the mice were analyzed using lesion severity scoring, histological analysis, flow cytometry, reverse transcription-quantitative polymerase chain reaction, western blotting and ELISA, in order to investigate the anti-AD effects of paeonol. In addition, western blotting and ELISA were conducted for in vitro analysis of P815 cells. The results demonstrated that oral administration of paeonol inhibited the development of DNCB-induced AD-like lesions in the BALB/c mice by reducing severity of the lesions, epidermal thickness and mast cell infiltration; this was accompanied by reduced levels of immunoglobulin E and inflammatory cytokines [interleukin (IL)-4, histamine, IL-13, IL-31 and thymic stromal lymphopoietin], along with regulation of the T helper (Th) cell subset (Th1/Th2) ratio. Application of paeonol also reduced the protein expression levels of phosphorylated (p)-p38 and p-extracellular signal-regulated kinase (ERK) in skin lesions. In vitro, paeonol reduced the expression levels of tumor necrosis factor-α and histamine in P815 cells, and inhibited p38/ERK/mitogen-activated protein kinase signaling. The present findings indicated that paeonol may relieve dermatitis by acting on cluster of differentiation 4+ T and mast cells; therefore, paeonol may represent a potential therapeutic strategy for the treatment of allergic inflammatory conditions via immunoregulation.
Rapamycin attenuates articular cartilage degeneration by inhibiting β-catenin in a murine model of osteoarthritis

ABSTRACT Purpose: To investigate whether systemic injection of rapamycin attenuates articular cartilage degeneration by inhibiting β-catenin in a murine model of osteoarthritis (OA). Materials and methods: Ten-week-old male C57BL/6j wild-type (WT) mice and SOST-knockout (SOST−/−) mice were randomized to a sham group, a vehicle-treated group, and a rapamycin-treated group. Mice in the vehicle-treated group underwent destabilizing of the medial meniscus (DMM) in the right knee, and were then treated with vehicle. Mice in the rapamycin treatment group underwent DMM and were treated with rapamycin. Safranin O-Fast green staining and Osteoarthritis Research Society International (OARSI) modified Mankin score were used to evaluate the histopathological features of the articular cartilage in the knee. The expression of light chain 3 (LC3) was evaluated by immunofluorescence, whereas the expression of ATG5, matrix metallopeptidase 13 (MMP-13), vascular endothelial growth factor (VEGF), sclerostin, and β-catenin were evaluated by immunohistochemistry. TUNEL staining was used to determine apoptosis of chondrocytes. Results: In vehicle-treated mice when compared with mice in the sham group, the OARSI scores, expression of MMP-13, VEGF, sclerostin, β-catenin, and chondrocyte apoptosis were significantly increased, whereas the expression of LC3 and ATG5 were significantly decreased. A systemic injection of rapamycin activated chondrocyte autophagy, which increased the expression of LC3 and ATG-5, and reduced OARSI scores, the expression of β-catenin, MMP-13, and VEGF, and chondrocyte apoptosis in rapamycin treated mice when compared with vehicle-treated mice. Conclusions: Systemic injection of rapamycin attenuated articular cartilage degeneration by inhibiting β-catenin in a murine model of OA.