Miracle-dz/UniFAR-FTUs huggingface dataset:
Association Between Preoperative Oral Antibiotics and the Incidence of Postoperative Clostridium difficile Infection in Adults Undergoing Elective Colorectal Resection: A Systematic Review and Meta-analysis

Supplemental Digital Content is available in the text. BACKGROUND: The risk of postoperative Clostridium difficile infection in patients receiving preoperative oral antibiotics remains controversial and a potential barrier for implementation. OBJECTIVE: The purpose of this study was to determine the association between preoperative oral antibiotics and the incidence of postoperative C difficile infection in patients undergoing colorectal surgery. DATA SOURCES: Medline, PubMed (not Medline), Embase, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Web of Science were searched for articles published up to September 2018. STUDY SELECTION: Randomized controlled trials and observational studies that compared bowel preparation regimens in adult patients who underwent colorectal surgery were selected. MAIN OUTCOME MEASURE: The incidence of postoperative C difficile infection in adults receiving oral antibiotics versus no oral antibiotics was used as the primary outcome. ORs were pooled using generalized linear/mixed effects models. RESULTS: Fourteen randomized controlled trials and 13 cohort studies comparing bowel preparation with oral antibiotics to those without oral antibiotics were identified. The pooled OR from 4 eligible randomized controlled trials was suggestive of a greater odds of C difficile infection in the oral antibiotic group (OR = 4.46 (95% CI, 0.96–20.66)); however, the absolute incidence of C difficile infection was extremely low (total 11 events among 2753 patients). The pooled OR from 6 eligible cohort studies did not demonstrate a significant difference in the odds of C difficile infection (OR = 0.88 (95% CI, 0.51–1.52)); again, a very low absolute incidence of C difficile infection was identified (total 830 events among 59,960 patients). LIMITATIONS: This meta-analysis was limited by the low incidence of C difficile infection reported in the studies and the low number of randomized controlled trials included. CONCLUSIONS: The incidence of C difficile infection in patients who undergo colorectal surgery is very low, regardless of bowel preparation regimen used. Considering the beneficial role of oral antibiotics in reducing surgical site infection, the fear for C difficile infection is not sufficient to omit oral antibiotics in this setting. SYSTEMATIC REVIEW REGISTRATION NUMBER: PROSPERO – IDCRD42018092148.
Lower risk of stroke with a vegetarian diet

In this issue of Neurology®, Chiu et al.1 report that a vegetarian diet reduced the risk of stroke in 2 cohorts of Buddhist adherents in Taiwan, who refrained from alcohol and tobacco. The low overall risk of stroke likely reflects the mean age at baseline of only ∼50 years in both cohorts and the relatively short duration of follow-up (5–7 years in cohort 1 and 9 years in cohort 2). In both cohorts, ∼30% followed a vegetarian diet. Importantly, only ∼25% of vegetarians were men.
An Engineered Infected Epidermis Model for In Vitro Study of the Skin’s Pro-Inflammatory Response

Wound infection is a major clinical challenge that can significantly delay the healing process, can create pain, and requires prolonged hospital stays. Pre-clinical research to evaluate new drugs normally involves animals. However, ethical concerns, cost, and the challenges associated with interspecies variation remain major obstacles. Tissue engineering enables the development of in vitro human skin models for drug testing. However, existing engineered skin models are representative of healthy human skin and its normal functions. This paper presents a functional infected epidermis model that consists of a multilayer epidermis structure formed at an air-liquid interface on a hydrogel matrix and a three-dimensionally (3D) printed vascular-like network. The function of the engineered epidermis is evaluated by the expression of the terminal differentiation marker, filaggrin, and the barrier function of the epidermis model using the electrical resistance and permeability across the epidermal layer. The results showed that the multilayer structure enhances the electrical resistance by 40% and decreased the drug permeation by 16.9% in the epidermis model compared to the monolayer cell culture on gelatin. We infect the model with Escherichia coli to study the inflammatory response of keratinocytes by measuring the expression level of pro-inflammatory cytokines (interleukin 1 beta and tumor necrosis factor alpha). After 24 h of exposure to Escherichia coli, the level of IL-1β and TNF-α in control samples were 125 ± 78 and 920 ± 187 pg/mL respectively, while in infected samples, they were 1429 ± 101 and 2155.5 ± 279 pg/mL respectively. However, in ciprofloxacin-treated samples the levels of IL-1β and TNF-α without significant difference with respect to the control reached to 246 ± 87 and 1141.5 ± 97 pg/mL respectively. The robust fabrication procedure and functionality of this model suggest that the model has great potential for modeling wound infections and drug testing.
Screening of Polyphenols and Antioxidative Activity in Industrial Beers

Antioxidative molecules, such as polyphenols can preserve and prolong the freshness of packaged beers. The aim of this work was to assess the content of polyphenolic compounds (by Folin-Ciocalteu and standard European Brewery Convention method) in different types of industrially produced beers (lager, pilsner, black and dark), packaged in brown glass bottles. The results of this research indicate that there are significant changes in polyphenol concentrations in correlation with beer type. Polyphenolic content was highest in dark and black beers. Antioxidative activity was also more pronounced in dark and black beers. Most prominent phenolic acid in all samples was gallic acid. Two samples of dark and three samples of black beers had >10 mg/100 mL of this polyphenol, with maximal value of 14.22 mg/100 mL in sample CK (black beer). This would indicate that black beers are richer in polyphenolic content than the light (lager and pilsner) beers and the moderate consumption of such beer could contribute to the health of consumers.
Impact of Sex Difference on the Discordance of Revascularization Decision Making Between Fractional Flow Reserve and Diastolic Pressure Ratio During the Wave‐Free Period

Background Sex difference in fractional flow reserve (FFR) and resting index has not been fully clarified. We sought to investigate the impact of sex on the discordance of revascularization decision making between FFR and diastolic pressure ratio during the diastolic wave‐free period (dPRWFP). Methods and Results A total of 759 angiographically intermediate lesions with 30% to 80% diameter stenosis by quantitative coronary angiography in 577 patients in whom FFR and dPRWFP were measured were investigated. dPRWFP was measured during the wave‐free window of 5 heart cycles at an independent core laboratory. FFR ≤0.80 and dPRWFP ≤0.89 were considered positive studies. A total of 164 vessels in 126 women (21.6%) and 595 vessels in 451 men (78.4%) were included. In lesions with negative dPRWFP, positive FFR was less frequently observed in women (13 of 73; 17.8%) than in men (97 of 286; 33.9%) (P=0.009). In lesions with positive dPRWFP, the frequency of negative FFR was observed in 22 of 91 vessels (24.2%) in women and 51 of 309 vessels (16.5%) in men, which did not reach statistical significance (P=0.098). In multivariable analyses, female sex was independently associated with FFR‐dPRWFP discordance both in negative dPRWFP cohort (odds ratio, 0.44; 95% CI, 0.21–0.98; P=0.036) and in positive dPRWFP cohort (odds ratio, 2.41; 95% CI, 1.17–4.96; P=0.017) after adjustment for age, weight, quantitative coronary angiography data, and baseline physiological indexes. Conclusions The frequency of FFR‐dPRWFP discordance was significantly associated with sex, which may indicate potential shift of optimal threshold of either FFR or dPRWFP, or both of them, according to sex.
Grading Gliomas Capability: Comparison between Visual Assessment and Apparent Diffusion Coefficient (ADC) Value Measurement on Diffusion-Weighted Imaging (DWI)

Background: To compare diagnostic accuracy between DWI visual scale assessment and ADC value measurement of solid portion of the tumor in grading gliomas. Methods: This retrospective study included 38 patients who had pathologically proven gliomas between January 2013 and August 2018 with 18 low grade and 20 high grade tumors. All patients underwent MRI and biopsy. Two readers reviewed DWI visual scale independently. Disagreement was resolved by consensus. One reviewer measured ADC value of entire solid part of the tumor in single axial slice with greatest dimension of tumor which was chosen by consensus. Two data sets of visual scale and ADC value were analyzed and comparison of diagnostic accuracy in glioma grading was done by using area under the curve (AUC) of receiver operating characteristic curve (ROC). Results: Visual scale and ADC value could be used to distinguish between low and high grade gliomas with a statistically significant difference. (P-value 0.002 and <0.001). Almost all high grade gliomas had visual scale 5. The sensitivity, specificity, PPV NPV and accuracy were 50%, 100%, 100% , 64.3%,73.68% respectively. The cutoff level for the ADC value was determined to be 1119.48 x10-6 mm2/s in differentiation between low and high grade gliomas with the sensitivity, specificity, PPV, NPV, accuracy of 90%, 88.89% , 90%, 88.9% and 89.47% respectively. There was no statistically significant difference(P-value = 0.163). Conclusion: Both Visual scale and ADC value were capable of differentiating between low and high grade gliomas. Although visual scale may not replace ADC measurement, larger scale prospective study is needed for validate this initial result.
Effects of Pre-Diapause Temperature and Body Weight on the Diapause Intensity of the Overwintering Generation of Bactrocera minax (Diptera: Tephritidae)

Abstract The Chinese citrus fruit fly, Bactrocera minax (Enderlein), is an economically important pest of citrus. The fly has an obligatory pupal diapause in soil from November to March. However, techniques for predicting or determining the emergence of the adult have, thus far, not been well documented. In this study, we investigated the effects of different pre-diapause temperatures (8, 12, 16, and 20°C) and pupal body weight (five groups according to pupal weight: G-58, 55.0–61.0 mg; G-68, 65–71 mg; G-78, 75–81 mg; G-88, 85–91 mg; G-95, 92–98 mg) on pupal period (the indicator of diapause intensity). The pupal period of B. minax larvae pupated at 8°C was 193.41 d, which was significantly shorter than that of larvae incubated at higher temperatures, suggesting that there was a lower diapause intensity for larvae pupated at lower pre-diapause temperatures. There were also significant differences in the pupal periods at different pupal body weights. The pupal period of G-58 was significantly shorter than that of the heavier groups (G-88 and G-95), and the pupal period increased with increasing pupal body weight in the five groups. Moreover, the pupal period of B. minax significantly and positively correlated to pupal body weight. These findings demonstrate that the pre-diapause temperature and pupal body weight are suitable indicators for predicting the pupal period of overwintering individuals, and the results of this study will contribute to the development of new and effective strategies for predicting the occurrence and population dynamics of B. minax adult.
New Evidences of Antibacterial Effects of Cranberry Against Periodontal Pathogens

The worrying rise in antibiotic resistances emphasizes the need to seek new approaches for treating and preventing periodontal diseases. The purpose of this study was to evaluate the antibacterial and anti-biofilm activity of cranberry in a validated in vitro biofilm model. After chemical characterization of a selected phenolic-rich cranberry extract, its values for minimum inhibitory concentration and minimum bactericidal concentration were calculated for the six bacteria forming the biofilm (Streptococcus oralis, Actinomyces naeslundii, Veillonella parvula, Fusobacterium nucleatum, Porphyromonas gingivalis, and Aggregatibacter actinomycetemcomitans). Antibacterial activity of the cranberry extract in the formed biofilm was evaluated by assessing the reduction in bacteria viability, using quantitative polymerase chain reaction (qPCR) combined with propidium monoazide (PMA), and by confocal laser scanning microscopy (CLSM), and anti-biofilm activity by studying the inhibition of the incorporation of different bacteria species in biofilms formed in the presence of the cranberry extract, using qPCR and CLSM. In planktonic state, bacteria viability was significantly reduced by cranberry (p < 0.05). When growing in biofilms, a significant effect was observed against initial and early colonizers (S. oralis (p ≤ 0.017), A. naeslundii (p = 0.006) and V. parvula (p = 0.010)) after 30 or 60 s of exposure, while no significant effects were detected against periodontal pathogens (F. nucleatum, P. gingivalis or A. actinomycetemcomitans (p > 0.05)). Conversely, cranberry significantly (p < 0.001 in all cases) interfered with the incorporation of five of the six bacteria species during the development of 6 h-biofilms, including P. gingivalis, A. actinomycetemcomitans, and F. nucleatum. It was concluded that cranberry had a moderate antibacterial effect against periodontal pathogens in biofilms, but relevant anti-biofilm properties, by affecting bacteria adhesion in the first 6 h of development of biofilms.
Hyperparathyroidism in Patients With X‐Linked Hypophosphatemia

X‐linked hypophosphatemia (XLH) is characterized by increased activity of circulating FGF23 resulting in renal phosphate wasting and abnormal bone mineralization. Hyperparathyroidism may develop in XLH patients; however, its prevalence, pathogenesis, and clinical presentation are not documented. This observational study (CNIL 171036 v 0) recruited XLH adult patients in a single tertiary referral center. Each patient was explored in standardized conditions and compared with two healthy volunteers, matched for sex, age, and 25‐OH vitamin D concentrations. The primary endpoint was the proportion of patients with hyperparathyroidism. The secondary endpoints were the factors influencing serum parathyroid hormone (PTH) concentrations and the prevalence of hypercalcemic hyperparathyroidism. Sixty‐eight patients (51 women, 17 men) were enrolled and matched with 136 healthy volunteers. Patients had higher PTH concentrations compared with healthy controls (53.5 ng/L, interquartile range [IQR] 36.7–72.7 versus 36.0 ng/L, IQR 27.7–44.0, p < .0001). Hyperparathyroidism was observed in 17 patients of 68 (25%). In patients, a positive relationship between PTH and calcium concentrations and a negative relationship between PTH and phosphate concentrations were observed. Seven (10%) patients (3 premenopausal women, 1 postmenopausal woman, and 3 men) were diagnosed with hypercalcemic hyperparathyroidism. All underwent parathyroid surgery, with consecutive normalization of calcium and PTH concentrations. Hyperparathyroidism is a frequent complication in XLH adult patients. Disruption of the physiological regulation of PTH secretion contributes to parathyroid disease. Early‐onset hypercalcemic hyperparathyroidism can be effectively and safely cured by surgical resection. © 2020 American Society for Bone and Mineral Research.
The Inhibitory Roles of Vitamin K in Progression of Vascular Calcification

Vitamin K is a fat-soluble vitamin that is indispensable for the activation of vitamin K-dependent proteins (VKDPs) and may be implicated in cardiovascular disease (CVD). Vascular calcification is intimately associated with CV events and mortality and is a chronic inflammatory process in which activated macrophages promote osteoblastic differentiation of vascular smooth muscle cells (VSMCs) through the production of proinflammatory cytokines such as IL-1β, IL-6, TNF-α, and oncostatin M (OSM) in both intimal and medial layers of arterial walls. This process may be mainly mediated through NF-κB signaling pathway. Vitamin K has been demonstrated to exert anti-inflammatory effects through antagonizing NF-κB signaling in both in vitro and in vivo studies, suggesting that vitamin K may prevent vascular calcification via anti-inflammatory mechanisms. Matrix Gla protein (MGP) is a major inhibitor of soft tissue calcification and contributes to preventing both intimal and medial vascular calcification. Vitamin K may also inhibit progression of vascular calcification by enhancing the activity of MGP through facilitating its γ-carboxylation. In support of this hypothesis, the procalcific effects of warfarin, an antagonist of vitamin K, on arterial calcification have been demonstrated in several clinical studies. Among the inactive MGP forms, dephospho-uncarboxylated MGP (dp-ucMGP) may be regarded as the most useful biomarker of not only vitamin K deficiency, but also vascular calcification and CVD. There have been several studies showing the association of circulating levels of dp-ucMGP with vitamin K intake, vascular calcification, mortality, and CVD. However, additional larger prospective studies including randomized controlled trials are necessary to confirm the beneficial effects of vitamin K supplementation on CV health.
Structure Elucidation of Urinary Metabolites of Fentanyl and Five Fentanyl Analogs using LC-QTOF-MS, Hepatocyte Incubations and Synthesized Reference Standards

Abstract Fentanyl analogs constitute a particularly dangerous group of new psychoactive compounds responsible for many deaths around the world. Little is known about their metabolism, and studies utilizing liquid chromatography–quadrupole time-of-flight mass spectrometry (LC–QTOF-MS) analysis of hepatocyte incubations and/or authentic urine samples do not allow for determination of the exact metabolite structures, especially when it comes to hydroxylated metabolites. In this study, seven motifs (2-, 3-, 4- and β-OH as well as 3,4-diOH, 4-OH-3-OMe and 3-OH-4-OMe) of fentanyl and five fentanyl analogs, acetylfentanyl, acrylfentanyl, cyclopropylfentanyl, isobutyrylfentanyl and 4F-isobutyrylfentanyl were synthesized. The reference standards were analyzed by LC–QTOF-MS, which enabled identification of the major metabolites formed in hepatocyte incubations of the studied fentanyls. By comparison with our previous data sets, major urinary metabolites could tentatively be identified. For all analogs, β-OH, 4-OH and 4-OH-3-OMe were identified after hepatocyte incubation. β-OH was the major hydroxylated metabolite for all studied fentanyls, except for acetylfentanyl where 4-OH was more abundant. However, the ratio 4-OH/β-OH was higher in urine samples than in hepatocyte incubations for all studied fentanyls. Also, 3-OH-4-OMe was not detected in any hepatocyte samples, indicating a clear preference for the 4-OH-3-OMe, which was also found to be more abundant in urine compared to hepatocytes. The patterns appear to be consistent across all studied fentanyls and could serve as a starting point in the development of methods and synthesis of reference standards of novel fentanyl analogs where nothing is known about the metabolism.
Fungal allergen‐induced IL‐33 secretion involves cholesterol‐dependent, VDAC‐1‐mediated ATP release from the airway epithelium

Alternaria aeroallergens induce the release of ATP from human bronchial epithelial (HBE) cells by activating a conductive pathway involving voltage‐dependent anion channel‐1 (VDAC‐1) and by exocytosis of ATP localized within membrane vesicles. Inhibition of VDAC‐1 blocked Alternaria‐evoked Ca2+ uptake across the plasma membrane of HBE cells and interleukin (IL)‐33 release into the extracellular media. Reducing cholesterol content with a cholesterol scavenger (β‐methylcyclodextrin) or statin compound (simvastatin) blocked ATP and IL‐33 release by lowering the expression of VDAC‐1 in the plasma membrane. Pretreatment with simvastatin for 24 h also inhibited the increase in tight junction macromolecule permeability that occurs following Alternaria exposure. These results establish a novel role for VDAC‐1 as a mechanism underlying ATP release induced by fungal allergens and suggests a possible therapeutic use for cholesterol lowering compounds in reducing Alternaria‐stimulated allergic inflammation.
Presentation clinical, haematological and immunophenotypic features of 1081 patients with GPI‐deficient (paroxysmal nocturnal haemoglobinuria) cells detected by flow cytometry

A retrospective analysis of presentation clinical, laboratory and immunophenotypic features of 1 081 patients with paroxysmal nocturnal haemoglobinuria (PNH) clones [glycosylphosphatidylinositol (GPI)‐deficient blood cells] identified at our hospital by flow cytometry over the past 25 years was undertaken. Three distinct clusters of patients were identified and significant correlations between presentation disease type and PNH clone sizes were evident. Smaller PNH clones predominate in cytopenic and myelodysplastic subtypes; large PNH clones were associated with haemolytic, thrombotic and haemolytic/thrombotic subtypes. Rare cases with an associated chronic myeloproliferative disorder had either large or small PNH clones. Cytopenia was a frequent finding, highlighting bone marrow failure as the major underlying feature associated with the detection of PNH clones in the peripheral blood. Red cell PNH clones showed significant correlations between the presence of type II (partial GPI deficiency) red cells and thrombotic disease. Haemolytic PNH was associated with type III (complete GPI deficiency) red cell populations of >20%. Those with both haemolytic and thrombotic features had major type II and type III red cell populations. Distinct patterns of presentation age decade were evident for clinical subtypes with a peak incidence of haemolytic PNH in the 30–49 year age group and a biphasic age distribution for the cytopenia group.
Revealing the epigenetic effect of temozolomide on glioblastoma cell lines in therapeutic conditions

Temozolomide (TMZ) is a drug of choice in glioblastoma treatment. Its therapeutic applications expand also beyond high grade gliomas. However, a significant number of recurrences and resistance to the drug is observed. The key factor in each chemotherapy is to achieve the therapeutic doses of a drug at the pathologic site. Nonetheless, the rate of temozolomide penetration from blood to cerebrospinal fluid is only 20–30%, and even smaller into brain intestinum. That makes a challenge for the therapeutic regimens to obtain effective drug concentrations with minimal toxicity and minor side effects. The aim of our research was to explore a novel epigenetic mechanism of temozolomide action in therapeutic conditions. We analyzed the epigenetic effects of TMZ influence on different glioblastoma cell lines in therapeutically achieved TMZ concentrations through total changes of the level of 5-methylcytosine in DNA, the main epigenetic marker. That was done with classical approach of radioactive nucleotide post-labelling and separation on thin-layer chromatography. In the range of therapeutically achieved temozolomide concentrations we observed total DNA hypomethylation. The significant hypermethylating effect was visible after reaching TMZ concentrations of 10–50 μM (depending on the cell line). Longer exposure time promoted DNA hypomethylation. The demethylated state of the glioblastoma cell lines was overcome by repeated TMZ applications, where dose-dependent increase in DNA 5-methylcytosine contents was observed. Those effects were not seen in non-cancerous cell line. The increase of DNA methylation resulting in global gene silencing and consecutive down regulation of gene expression after TMZ treatment may explain better glioblastoma patients’ survival.