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Artificial intelligence (AI) is widely used in the field of education at present, but people know little about its possible impacts, especially on the physical and mental development of the educated. It is important to explore the possible impacts of the application of artificial intelligence in education (AIEd) in order to avoid the possible adverse effects. Prior research has focused on theory to the exclusion of the psychological impact of AIEd, and the empirical research was relatively lacking. This study aimed to identify the influence of AIEd on adolescents' social adaptability via social support. A total of 1332 students were recruited using random sampling from 13 Artificial Intelligence Curriculum Reform Experimental Schools in Guangzhou, Southern China, completed the survey. There were 342 primary school students (Meanage = 10.6), 351 junior high school students (Meanage = 13.1), and 639 senior high school students (Meanage = 15.8). Results showed that AIEd has a negative impact on adolescents' social adaptability, and is significantly negatively correlated with social adaptability and family support, but there is no significant correlation with school support. AIEd could not only affect social adaptability directly, but also could affected it through the family support.

Background: Uric acid nephropathy (UN) is a complication of hyperuricemia (HUA), which has a great impact on people's lives. Here, we evaluated the therapeutic potential of total flavonoids of Phellinus igniarius (TFPI) in vivo and studied the anti UN effect of TFPI in vitro. Methods: Hyperuricemia was induced by intraperitoneal injection of potassium oxonate in ICR mice. After intervention with TFPI, we evaluated the levels of serum uric acid (UA) and creatinine (CR), and the contents of xanthine oxidase (XOD) and adenosine deaminase (ADA) in liver. To explore the effect and molecular mechanism of TFPI on UN, we treated HK-2 cells with monosodium urate (MSU) to study the effect of TFPI on apoptosis and inflammation. In addition, to explore the mechanism of TFPI on uric acid transport we evaluated the relationship between uric acid transporter ABCG2 and inflammatory signaling pathway TLR4-NLRP3. Results: In the model mice, TFPI significantly decreased the levels of UA and Cr, which may be related to the inhibition of XOD enzyme activity. In HK-2 cells, the response of TFPI to MSU can effectively inhibit apoptosis and activation of TLR4-NLRP3 signaling pathway and promote the expression of ABCG2. Conclusions: TFPI can significantly inhibit the release of inflammatory factors and promote the expression of ABCG2 by targeting TLR4 receptor and NLRP3 inflammasome. And targeted inhibition of XOD enzyme activity to reduce uric acid level and inhibit the development of UN.

Several risk factors have been identified for the development of gastric adenocarcinoma (GAC), where the control group was usually a healthy population. However, it is unclear at what stage known risk factor exert their influence toward the progression to cancer. Based on the Wuwei Cohort, we enrolled 1,739 patients with chronic non-atrophic gastritis (no-CAG), 3,409 patients with chronic atrophic gastritis (CAG), 1,757 patients with intestinal metaplasia (IM), 2,239 patients with low-grade dysplasia (LGD), and 182 patients with high-grade dysplasia (HGD) or GAC to assess the risk factors between each two consecutive stages from no-CAG to GAC/HGD using adjusted logistic regression. We found that different groups of risk factors were associated with different stages. Age, occupation of farmer, low annual family income, Helicobacter pylori (H. pylori) infection, drinking, eating hot food, histories of gastritis and peptic ulcer were associated with the development of CAG. Age, illiteracy, H. pylori infection, smoking, eating hot food, eating quickly, and histories of gastritis and gallbladder diseases were associated with the progression to IM from CAG. Male, occupation of farmer and history of peptic ulcer were associated with the development of LGD from IM. Age, male and polyp history appeared to be risk factors associated with the development of GAC/HGD from LGD. In conclusion, it seems that most risk factors function more as a set of switches that initiated the GAC carcinogenesis. H. Pylori eradication and control of other risk factors should be conducted before IM to decrease the incidence of GAC.

Proliferative vitreoretinopathy(PVR)is a serious complication arisen from ocular trauma, diabetic retinopathy, vascular retinopathy, inflammatory retinopathy and other ocular diseases. It is also the most important reason for the failure of rhegmatogenous retinal detachment surgery, which is a great threat of visual function. A large number of studies have proved that the main risk factor for PVR is the damage of blood-retinal barrier, in which retinal pigment epithelial(RPE)cells are stimulated by cytokines in the vitreous cavity. RPE cells underwent epithelial-mesenchymal transition(EMT), which transformed into fibroblasts. The cell morphology changed, the tight junctions between cells disappeared, the cell polarity lost, and the proliferation, migration, and invasion abilities were enhanced. A contractile fibrous proliferative membrane is formed on the anterior surface or under the retina. The fibrous proliferative membrane will lead to the retina folds, pull the retina and lead to retinal detachment, which will eventually lead to vision loss or even blindness. Nowadays, plenty of studies investigating the prevention and treatment of PVR have been carried out at home and abroad. In this review, we briefly illustrated the signaling pathways related to epithelial-mesenchymal transformation in RPE cells and the treatment of PVR.

Abstract Background Kluyveromyces marxianus is a promising cell factory for producing bioethanol and that raised a demand for a high yield of heterologous proteins in this species. Expressions of heterologous proteins usually lead to the accumulation of misfolded or unfolded proteins in the lumen of the endoplasmic reticulum (ER) and then cause ER stress. To cope with this problem, a group of ER stress response target genes (ESRTs) are induced, mainly through a signaling network called unfolded protein response (UPR). Characterization and modulation of ESRTs direct the optimization of heterologous expressions. However, ESRTs in K. marxianus have not been identified so far. Results In this study, we characterized the ER stress response in K. marxianus for the first time, by using two ER stress-inducing reagents, dithiothreitol (DTT) and tunicamycin (TM). Results showed that the Kar2–Ire1–Hac1 pathway of UPR is well conserved in K. marxianus. About 15% and 6% of genes were upregulated during treatment of DTT and TM, respectively. A total of 115 upregulated genes were characterized as ESRTs, among which 97 genes were identified as UPR target genes and 37 UPR target genes contained UPR elements in their promoters. Genes related to carbohydrate metabolic process and actin filament organization were identified as new types of UPR target genes. A total of 102 ESRTs were overexpressed separately in plasmids and their effects on productions of two different lignocellulolytic enzymes were systematically evaluated. Overexpressing genes involved in carbohydrate metabolism, including PDC1, PGK and VID28, overexpressing a chaperone gene CAJ1 or overexpressing a reductase gene MET13 substantially improved secretion expressions of heterologous proteins. Meanwhile, overexpressing a novel gene, KLMA_50479 (named ESR1), as well as overexpressing genes involved in ER-associated protein degradation (ERAD), including HRD3, USA1 andYET3, reduced the secretory expressions. ESR1 and the aforementioned ERAD genes were deleted from the genome. Resultant mutants, except the yet3Δ mutant, substantially improved secretions of three different heterologous proteins. During the fed-batch fermentation, extracellular activities of an endoxylanase and a glucanase in hrd3Δ cells improved by 43% and 28%, respectively, compared to those in wild-type cells. Conclusions Our results unveil the transcriptional scope of the ER stress response in K. marxianus and suggest efficient ways to improve productions of heterologous proteins by manipulating expressions of ESRTs.

BackgroundPrevious studies suggested that gut dysbacteriosis may promote the occurrence of chronic kidney disease (CKD), and probiotic, prebiotic, or yogurt supplements may alleviate CKD progression. This study aims to examine the association between probiotic, prebiotic, or yogurt supplements and the risk of CKD using the data from NHANES.MethodsThis study was designed to prospectively search data from the National Health and Nutrition Examination Survey (NHANES) (2011–2020). We examined dietary supplements and prescription medication labels to identify probiotic, or prebiotic product, and yogurt consumption during the dietary interview. The diagnosis of CKD was determined by the value of glomerular filtration rate (eGFR) and albumin creatinine ratio (ACR).ResultsThe study enrolled a total of 6,522 individuals. The prevalence of CKD was lower in the probiotic, prebiotic, or yogurt consumption group [age-adjusted odds ratio (OR): 0.77, 95% CI: 0.62–0.95, P = 0.02; multivariable-adjusted OR: 0.86, 95% CI: 0.69–1.07, P = 0.05]. Furthermore, 32% reduced risk was observed in the older group aged 55 years or older, and 32% reduced risk was also observed in the female population. Probiotic, or prebiotic, or yogurt supplements was associated a 12% reduction in moderate risk of CKD and an 11% reduction in very high risk of CKD.ConclusionOur results suggest that probiotic, prebiotic, or yogurt supplements may contribute to the prevention of CKD and relieve its progression risk, especially in the female population and older population who were aged 55 years or older.

In this study, using chitosan (CS) and carboxymethyl cellulose (CMC) as backbone and introducing citric acid (CA)to enhance the electrostatic interaction of the system, citric acid/chitosan/carboxymethyl cellulose (CA/CS/CMC) aerogel is obtained by simple freeze-drying. CA/CS/CMC composite aerogel exhibits light weight, low density, high porosity, outstanding hydrophilic and water retention properties, and satisfactory underwater oleophobicity. The water adsorption capacity of the obtained aerogels can reach 43.87–80.28 g/g, which are far more than that of carboxymethyl cellulose and chitosan aerogels (14.27–20.08 g/g). In addition, with strong hydrophilicity, underwater oleophobicity and water retention endowed by the rough internal microstructure and the rich hydroxyl, amino, and carboxyl groups, the fabricated aerogel can also be used as a filter to achieve effective separation of oil-in-water emulsions and oil/water mixtures. The separation efficiency of aerogel for oil/water mixtures are higher than 90.7%. Because the developed preparation method is green, simple and mild and the raw materials are readily available and environmentally friendly, the obtained CA/CS/CMC aerogel with strong water absorption capacity and good separation efficiency displays a promising application in water-oil separation.

Mapping of the HIV Env surface epitopes targeted by broadly neutralizing antibodies (bNAbs) is of great interest for HIV-1 vaccine design. Here, the authors present the 3.2 Å cryo-EM structure of the bNAb M4008_N1 in complex with BG505 DS-SOSIP, an engineered native-like Env trimer and observe that the bNAb epitope is centered at the V3 crown and that M4008_N1 uses its CDR H3 to form an extended β-sheet with the β-hairpin of the V3 crown in a conformation stabilized in the prefusion trimer.

Abstract Background Dyspepsia is a common cause of physician visits. If and when endoscopy should be performed depend on the regions and the populations. This study aimed to identify the current risk factors predictive of upper gastrointestinal malignancy or peptic ulcer in China with high prevalence of gastric cancer. Methods A questionnaire was conducted among consecutive outpatients undergoing their first esophagogastroduodenoscopy for dyspepsia. Symptoms other than alarm symptoms in this study were defined as uncomplicated dyspepsia. Results 4310 outpatients (mean age 44, median 42, range 14–86) were included in the final analyses. Significant pathology was found in 13.8% (595/4310) patients including peptic ulcer (12.3%) and upper gastrointestinal malignancy (1.5%). Age, male sex and alarm symptoms were significantly associated with malignancy. The age cut-off identified for upper gastrointestinal malignancy was 56 years among patients with uncomplicated dyspepsia, which was similar to the combined cutoff of age and gender. Conclusions Age should be considered as the primary predictor for upper gastrointestinal malignancy in Chinese patients with uncomplicated dyspepsia. 56 could probably be the optimal age to identify those lesions in this population. Trial registration: Chictr.org (ChiCTR2000040775).

Abstract Background Hemicellulose acts as one factor contributing to the recalcitrance of lignocellulose that prevents cellulases to degrade the cellulose efficiently even in low quantities. Supplement of hemicellulases can enhance the performance of commercial cellulases in the enzymatic hydrolyses of lignocellulose. Kluyveromyce marxianus is an attractive yeast for cellulosic ethanol fermentation, as well as a promising host for heterologous protein production, since it has remarkable thermotolerance, high growth rate, and broad substrate spectrum etc. In this study, we attempted to coordinately express multiple hemicellulases in K. marxianus through a 2A-mediated ribosome skipping to self-cleave polyproteins, and investigated their capabilities for saccharification and ethanol production from corncobs. Results Two polycistronic genes IMPX and IMPαX were constructed to test the self-cleavage of P2A sequence from the Foot-and-Mouth Disease virus (FMDV) in K. marxianus. The IMPX gene consisted of a β-mannanase gene M330 (without the stop codon), a P2A sequence and a β-xylanase gene Xyn-CDBFV in turn. In the IMPαX gene, there was an additional α-factor signal sequence in frame with the N-terminus of Xyn-CDBFV. The extracellular β-mannanase activities of the IMPX and IMPαX strains were 21.34 and 15.50 U/mL, respectively, but the extracellular β-xylanase activity of IMPαX strain was much higher than that of the IMPX strain, which was 136.17 and 42.07 U/mL, respectively. Subsequently, two recombinant strains, the IXPαR and IMPαXPαR, were constructed to coordinately and secretorily express two xylantic enzymes, Xyn-CDBFV and β-D-xylosidase RuXyn1, or three hemicellulolytic enzymes including M330, Xyn-CDBFV and RuXyn1. In fed-batch fermentation, extracellular activities of β-xylanase and β-xylosidase in the IXPαR strain were 1664.2 and 0.90 U/mL. Similarly, the IMPαXPαR strain secreted the three enzymes, β-mannanase, β-xylanase, and β-xylosidase, with the activities of 159.8, 2210.5, and 1.25 U/mL, respectively. Hemicellulolases of both strains enhanced the yields of glucose and xylose from diluted acid pretreated (DAP) corncobs when acted synergistically with commercial cellulases. In hybrid saccharification and fermentation (HSF) of DAP corncobs, hemicellulases of the IMPαXPαR strain increased the ethanol yield by 8.7% at 144 h compared with the control. However, both ethanol and xylose yields were increased by 12.7 and 18.2%, respectively, at 120 h in HSF of aqueous ammonia pretreated (AAP) corncobs with this strain. Our results indicated that coordinate expression of hemicellulolytic enzymes in K. marxianus promoted the saccharification and ethanol production from corncobs. Conclusions The FMDV P2A sequence showed high efficiency in self-cleavage of polyproteins in K. marxianus and could be used for secretory expression of multiple enzymes in the presence of their signal sequences. The IMPαXPαR strain coexpressed three hemicellulolytic enzymes improved the saccharification and ethanol production from corncobs, and could be used as a promising strain for ethanol production from lignocelluloses.

Abstract Background Canadians are known to be frequent users of emergency department (ED) care. However, the exchange of information from ED visits to family physicians (FPs) is not well known. Our objectives were to determine whether Canadian FPs received information about their patient’s ED visit and the patient characteristics related to the receipt of ED information. Methods This study was a descriptive record linkage study of FP Electronic Medical Record (EMR) data linked to health administrative data. Our study cohort included patients who had at least one ED visit in 2010 or 2015 in Ontario, Canada. An ED visit could include a transfer to or from another ED. The receipt of information from an ED note was examined in relation to patient age, sex, neighbourhood income quintiles, rurality and comorbidity. Results There were 26,609 patients in 2010 and 50,541 patients in 2015 with at least one ED visit. In 2010, 53.3% of FPs received an ED note for patients having a single ED visit compared to 41.0% in 2015. For patients with multiple ED visits, 58.2% of FPs received an ED note in 2010 compared to 45.7% in 2015. FPs were more likely to receive an ED note for patients not living in low income neighbourhoods, older patients, patients living in small urban areas and for patients having moderate comorbidity. FPs were less likely to receive a note for patients living in rural areas. Conclusions Community-based FPs are more likely to get information after an ED visit for their older and sicker patients. However, FPs do not receive any information from EDs for over half their patients. Electronic health record technologies and their adoption by ED providers need to improve the seamless transfer of information about the care provided in EDs to FPs in the community.

Abstract Background Previous studies have demonstrated the preclinical pharmacological and toxicological consistency, and clinical pharmacokinetic equivalence of bevacizumab biosimilar LY01008 with reference bevacizumab (Avastin). This randomized controlled trial aimed to compare the efficacy and safety of LY01008 with Avastin in first‐line treatment of Chinese patients with advanced or recurrent non‐squamous non‐small cell lung cancer (NSCLC). Methods Stage IIIB‐IV NSCLC patients with evaluable lesions, good physical status, and adequate organ functions from 67 centers across China were randomized in a ratio of 1:1 to receive LY01008 or Avastin 15 mg/kg intravenously in combination with paclitaxel/carboplatin (combined treatment) for 4‐6 cycles, followed by maintenance monotherapy with LY01008 until disease progression, intolerable toxicity, or death. The primary endpoint was objective response rate (ORR) in accordance with Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 confirmed by independent radiological review committees (IRRC). Secondary endpoints included disease control rate (DCR), duration of response (DoR), progression‐free survival (PFS), overall survival (OS), and safety. This study was registered in ClinicalTrials.gov (NCT03533127). Results Between December 15th, 2017, and May 15th, 2019, a total of 649 patients were randomized to the LY01008 (n = 324) or Avastin (n = 325) group. As of September 25th, 2019 for primary endpoint analysis, 589 patients received ORR evaluation, with a median number of combined treatment cycles of 5 (range 1‐6) and median duration of treatment of 3.0 (range 0.0‐5.1) months. ORR of response‐evaluable patients in the LY01008 and Avastin groups were 48.5% and 53.0%, respectively. The stratified ORR ratio was 0.91 (90% CI 0.80‐1.04, within the prespecified equivalence margin of 0.75‐1.33). Up to May 15th, 2020, with a median follow‐up of 13.6 (range 0.8‐28.4) months, no notable differences in DCR, median DoR, median PFS, median OS, and 1‐year OS rate were observed between the LY01008 and Avastin groups. There were no clinically meaningful differences in safety and immunogenicity across treatment groups. Conclusions LY01008 demonstrated similarity to Avastin in terms of efficacy and safety in Chinese patients with advanced or recurrent non‐squamous NSCLC. LY01008 combined with paclitaxel/carboplatin is expected to become a new treatment option for unresectable, metastatic, or recurrent non‐squamous NSCLC patients in the first‐line setting.

Introduction: Exposure to greenspace has been reported to reduce stroke mortality, but there is a lack of evidence regarding poststroke disability. This study aimed to investigate the association between long-term greenspace exposure and the risk of poststroke disability. Methods: Based on the China National Stroke Screening Survey from 2013 to 2019, a total of 65,892 visits from 28,085 stroke survivors with ≥ 2 visits were included in this longitudinal study. Long-term greenspace exposure was assessed by a 3-year average of the Normalized Difference Vegetation Index (NDVI) and the proportion of green land cover according to participants’ residential communities. Poststroke functional status was assessed with the modified Ranking Score (mRS) at each visit; a cutoff score > 2 indicated disability. Fixed effects regressions were used to examine the association of greenspace exposure with continuous mRS scores or binary indicators for disability. Results: The annual mean NDVI value was 0.369 (standard deviation = 0.120) for all visits among stroke survivors. With full adjustments, each 0.05 increase in NDVI was associated with a 0.056-unit (95 % confidence interval (CI): 0.034, 0.079) decrease in the mRS score and a 46.6 % (95 % CI: 10.0 %, 68.3 %) lower risk of poststroke disability. An L-shaped curve was observed for the nonlinear associations between NDVI and mRS score or disability. Additionally, each 1 % increase in grasslands, savannas, forest, and croplands was associated with 0.008- (95 % CI: 0.002, 0.014), 0.003- (95 % CI: 0.001, 0.005), 0.001- (95 % CI: −0.015, 0.018), and 0.002-unit (95 % CI: −0.003, 0.007) decreases in the mRS score, respectively. Conclusions: Increasing greenspace was inversely associated with mRS score. Greenspace planning can be a potential intervention to prevent poststroke disability.

K. marxianus is a promising cell factory for producing heterologous proteins. Oxidative stresses were raised during overexpression of heterologous proteins, leading to the shift of the redox state. How to measure the redox state of live K. marxianus cells without perturbing their growth remains a big challenge. Here, a fluorescence lifetime imaging (FLIM)-based method was developed in live K. marxianus cells. During the early exponential growth, K. marxianus cells exhibited an increased mean fluorescence lifetime (τ-mean) of NAD(P)H compared with Saccharomyces cerevisiae cells, which was consistent with the preference for respiration in K. marxianus cells and that for fermentation in S. cerevisiae cells. Upon oxidative stresses induced by high temperature or H2O2, K. marxianus cells exhibited an increased τ-mean in company with decreased intracellular NAD(P)H/NAD(P)+, suggesting a correlation between an increased τ-mean and a more oxidized redox state. The relationship between τ-mean and the expression level of a heterologous protein was investigated. There was no difference between the τ-means of K. marxianus strains which were not producing a heterologous protein. The τ-mean of a strain yielding a high level of a heterologous protein was higher than that of a low-yielding strain. The results suggested the potential application of FLIM in the non-invasive screen of high-yielding cells.

Abstract With the increasing demand for traditional Chinese medicine (TCM) in Portuguese-speaking countries (PSC), local regulatory systems and relevant legislation are still insufficient and lagging, even blank in some of them. This kind of unbalanced pace either makes users of TCM exposed in potential risk or eventually obstructs the long-term development of TCM in PSC. Despite existing tremendous studies on the internationalization of TCM, there are few studies specific to PSC. Thus, by a comprehensive desk review and typical case study, this article aims to summarize current situation of TCM in PSC by a cross-regional comparison, to identify various critical challenges, and further to provide an insightful reference to impel the development of TCM in PSC.

Abstract. The novel coronavirus (SARS-CoV-2) infection has become a heavy burden on global health. Although the coronavirus disease 2019 (COVID-19) may adversely affect multiple organs and systems of infected patients, to the best of our knowledge, there is little investigation of the SARS-CoV-2's impact on bone marrow. Our clinical and cytological findings in this case of severe COVID-19 infection provide novel insights into the pathogenesis of SARS-CoV-2 infection in the hematopoietic system. We recommend that physicians consider SARS-CoV-2 infection's effect on bone marrow in patients who are slow to recover and suggest that a better understanding of the bone marrow morphology in COVID-19-infected patients is needed.

Particulate Matter 2.5 (PM2.5) disrupts endocrine functions and may negatively affect sperm quality and quantity in males; however, the long-term effects and potential mechanisms of this effect are unknown. This study aimed to investigate the epigenetic mechanism of maternal exposure to PM2.5-induced inhibin B hypermethylation in male offspring. In this experiment design, pregnant C57BL/6 mice were treated with two doses of PM2.5 (4.8 and 43.2 mg/kg bw). The membrane control group was given a sampling membrane and the control group received nothing. Following the formation of the vaginal plug, intratracheal instillation of PM2.5 was administered every three days until delivery of the pups. To assess the effect of PM2.5 in vitro, TM4 cells, a Sertoli-like cell line, was treated with different concentrations (0, 25, 50, 100 μg/mL) of PM2.5 for 24 h. The results displayed that Sperm motility, as well as the number of adult offspring, was decreased in the PM2.5 exposed group relative to the untreated controls. Increased vacuolization was observed in the Sertoli cells of mice that were exposed to PM2.5 in utero. The levels of inhibin and testosterone were reduced and the levels of LH and FSH increased in the PM2.5 groups relative to the untreated controls. In vitro, PM2.5 resulted in cell cycle inhibition as well as increased apoptosis in TM4 cells. Moreover, PM2.5-induced inhibin B hypermethylation and activation of the p21/Cleaved Caspase-3 pathway resulted in TM4 cell apoptosis that was rescued through the use of a DNA methylation inhibitor. Together, our data suggest that prenatal exposure to PM2.5 results in inhibin B hypermethylation and can activate the p21/Cleaved Caspase-3 pathway, resulting in Sertoli cell apoptosis, aberrant secretion of androgen binding protein, and decreased testosterone, thus resulting in the inhibition of spermatogenesis.

Background: Children have a higher risk of medication errors (MEs) than adults. The Institute for Safe Medication Practice (ISMP) defined high-alert medications (HAMs) as a group of medications that could cause significant patient harm or even death when they are used in error. Nurses are actively involved in and responsible for patient care, especially in medication administration. This study aimed to estimate the knowledge, decision-making basis and confidence and decision support needs related to HAMs among pediatric nurses in China.Methods: A web-based, cross-sectional survey was conducted among pediatric nurses who were recruited from 14 member hospitals of the Pediatric Nursing Alliance of National Children’s Medical Center in China using a convenient sampling technique. Data were collected using a self-administered instrument composed of four parts: the demographic characteristics of participants, participants’ knowledge about HAMs, participants’ self-evaluation of the basis of and confidence in decision-making, and decision support needs regarding HAMs. Among the participants, the maximum score for HAM knowledge was 100. All data were entered and analyzed using SPSS 20.0.Results: A total of 966 nurses participated in this study. Nurses were found to have insufficient knowledge about HAMs, with a median (IQR) of 75.0 (70.0, 80.0), out of a maximum score of 100. Knowledge about HAM administration was significantly higher than that about HAM regulation, with a p value < 0.001. The three lowest-scoring items concerned HAM regulation, and the “Treat fentanyl skin patches as a regulated narcotic” item obtained the lowest score, with only 1/5 of respondents answering it correctly. Most participants reported that their basis for decision-making about HAMs was drug instructions (90.0%) or drug handbooks (81.9%) and evaluated their confidence in decision-making about HAMs as high or relatively high (84.6%). The decision-making difficulties when encountering HAMs focused on most stages of HAM administration, especially the appropriateness of prescriptions, checks, preparation and administration. The vast majority of participants assessed decision support as necessary or very necessary (92.0%), and the most popular options for decision support were computerized clinical decision support systems (46.4%) and real-time online communication with pharmacists (23.9%).Conclusion: Our study demonstrated the inadequacies in HAM knowledge, the basis and difficulty of decision-making, and decision support needs regarding HAMs in Chinese pediatric nurses. Nurses need greater support in HAM administration, including not only training but also adequate technology, mutually beneficial interprofessional collaboration, and a positive institutional culture.

This study explored the application of Kluyveromyces marxianus and Saccharomyces cerevisiae (commercial and wild type) in the alcoholic fermentation of Fuji apple juice under static conditions. Metabolome analyses revealed that ethyl esters, including ethyl hexanoate, ethyl decanoate, ethyl octanoate, octanoic acid and decanoic acid, were the dominant components in ciders fermented by the Saccharomyces yeasts. In the K. marxianus ciders, ethyl acetate, hexyl acetate, propyl acetate and acetic acid were the most abundant volatiles, suggesting that the cider fermented by K. marxianus might have a fruitier smell. Transcriptome analyses were adapted to gain insight into the differential metabolite patterns between K. marxianus and S. cerevisiae during cider fermentation. GO and KEGG enrichments revealed that the metabolic pathways of glucose, organic acids and amino acids during cider fermentation were quite different between these two yeasts. The K. marxianus strain exhibited a higher rate of glycolysis and ethanol fermentation than did Saccharomyces yeasts under oxygen-limited conditions. It also reduced the metabolic flux of acetate into acetyl-CoA and then into the TCA cycle, increasing the syntheses of ethyl acetate and relevant esters, which may affect its cell growth under anaerobic conditions but enriched the taste and variety of aromas in apple cider.

Anthraquinone compounds (ACs) could be efficiently degraded and detoxified by bacteria. However, the molecular mechanism of bacterial degradation and detoxification of ACs remains unclear. In this study, 1-aminoanthraquinone-2-sulfonate (ASA-2) was used as a model anthraquinone compound, the response mechanism of Rhodococcus pyridinivorans GF3 to ASA-2 using genomics and transcriptomics techniques was investigated. Comparative genome analysis showed that strain GF3 owned an especial gene region (Genes 1337–1399) containing the genes encoding cytochrome P450, monooxygenase, dehydrogenase and oxidoreductase, which did not commonly exist in Rhodococcus genus. The amino acid sequences of these genes were similar to those of the cleavage enzymes of anthraquinone ring in Aspergillus genus. Moreover, the transcriptions of Genes 1392–1394 (cytochrome 450 gene cluster) displayed 1.8–3.1-fold up-regulation under ASA-2 exposure. Meanwhile, as an intermediate product of ASA-2, catechol was degraded to acetyl-CoA, succinyl-CoA and pyruvate, resulting in the enhanced tricarboxylic acid cycle and ATP generation. This process also promoted the up-regulation of the genes encoding resistance, efflux, transporter and anti-oxidation pressure proteins, which were involved in resisting ASA-2 and maintaining the homeostasis of cells. These results provided us with a further understanding of the molecular mechanism of degradation and detoxification of ACs.

Abstract The growth and tolerance of Kluyveromyces marxianus at high temperatures decreased significantly in the synthetic medium (SM), which is commonly used in industrial fermentations. After 100 days of adaptive laboratory evolution, a strain named KM234 exhibited excellent tolerance at a high temperature, without loss of its growth ability at a moderate temperature. Transcriptomic analysis revealed that the KM234 strain decreased the expression of the ammonium (NH4+) transporter gene MEP3 and increased the synthesis of the amino acid carbon backbone, which may contribute greatly to the high‐temperature growth phenotype. High NH4+ content in SM significantly increased the reactive oxygen species (ROS) production at high temperatures and thus caused toxicity to yeast cells. Replacing NH4+ with organic nitrogen sources or increasing the concentration of potassium ions (K+) in the medium restored the growth of the wild‐type K. marxianus at a high temperature in SM. We also showed that the NH4+ toxicity mitigated by K+ might closely depend on the KIN1 gene. Our results provide a practical solution to industrial fermentation under high‐temperature conditions.

Abstract Background The assessment of retroperitoneal lymph node status in patients with locally advanced cervical cancer is still a problem. This study aimed to explore the choice of these assessment methods. Methods Laparoscopic retroperitoneal lymphadenectomy was performed in 96 patients with advanced cervical cancer. The positive rates of lymph node metastasis were analyzed. The values of computed tomography lymph node minimum axial diameter (MAD) and squamous cell carcinoma antigen (SCC-Ag), and their combination in predicting retroperitoneal lymph node metastasis were compared. High-risk factors for common iliac lymph node (CILN) and/or para-aortic lymph node (PALN) metastasis were analyzed. Results The lymph node metastasis rate was 62.50% and the CILN and/or PALN metastasis rate was 31.25%. Overall, 96 patients had 172 visible lymph nodes. The positive rate of lymph node metastasis was significantly higher in the MAD ≥1.0 cm group (83.33%) than in the 0.5 cm ≤ MAD

Lung cancer is the most common cancer and cause of cancer death in Canada, with approximately 50% of cases diagnosed at stage IV. Sociodemographic inequalities in lung cancer diagnosis have been documented, but it is not known if inequalities exist with respect to immigration status. We used multiple linked health-administrative databases to create a cohort of Ontarians 40–105 years of age who were diagnosed with an incident lung cancer between 1 April 2012 and 31 March 2017. We used modified Poisson regression with robust standard errors to examine the risk of diagnosis at late vs. early stage among immigrants compared to long-term residents. The fully adjusted model included age, sex, neighborhood-area income quintile, number of Aggregated Diagnosis Group (ADG) comorbidities, cancer type, number of prior primary care visits, and continuity of care. Approximately 62% of 38,788 people with an incident lung cancer from 2012 to 2017 were diagnosed at a late stage. Immigrants to the province were no more likely to have a late-stage diagnosis than long-term residents (63.5% vs. 62.0%, relative risk (RR): 1.01 (95% confidence interval (CI): 0.99–1.04), adjusted relative risk (ARR): 1.02 (95% CI: 0.99–1.05)). However, in fully adjusted models, people with more comorbidities were less likely to have a late-stage diagnosis (adjusted relative risk (ARR): 0.82 (95% CI: 0.80–0.84) for those with 10+ vs. 0–5 ADGs). Compared to adenocarcinoma, small cell carcinoma was more likely to be diagnosed at a late stage (ARR: 1.29; 95% CI: 1.27–1.31), and squamous cell (ARR: 0.89; 95% CI: 0.87–0.91) and other lung cancers (ARR: 0.93; 95% CI: 0.91–0.94) were more likely to be diagnosed at an early stage. Men were also slightly more likely to have late-stage diagnosis in the fully adjusted model (ARR: 1.08; 95% CI: 1.05–1.08). Lung cancer in Ontario is a high-fatality cancer that is frequently diagnosed at a late stage. Having fewer comorbidities and being diagnosed with small cell carcinoma was associated with a late-stage diagnosis. The former group may have less health system contact, and the latter group has the lung cancer type most closely associated with smoking. As lung cancer screening programs start to be implemented across Canada, targeted outreach to men and to smokers, increasing awareness about screening, and connecting every Canadian with primary care should be system priorities.

Abstract Background Gender inequality varies across countries and is associated with poor outcomes including violence against women and depression. Little is known about the relationship of source county gender inequality and poor health outcomes in female immigrants. Methods We used administrative databases to conduct a cohort study of 299,228 female immigrants ages 6–29 years becoming permanent residence in Ontario, Canada between 2003 and 2017 and followed up to March 31, 2020 for severe presentations of suffering assault, and selected mental health disorders (mood or anxiety, self-harm) as measured by hospital visits or death. Poisson regression examined the influence of source-country Gender Inequality Index (GII) quartile (Q) accounting for individual and country level characteristics. Results Immigrants from countries with the highest gender inequality (GII Q4) accounted for 40% of the sample, of whom 83% were from South Asia (SA) or Sub-Saharan Africa (SSA). The overall rate of assault was 10.9/10,000 person years (PY) while the rate of the poor mental health outcome was 77.5/10,000 PY. Both GII Q2 (Incident Rate Ratio (IRR): 1.48, 95% Confidence Interval (CI): 1.08, 2.01) and GII Q4 (IRR: 1.58, 95%CI: 1.08, 2.31) were significantly associated with experiencing assault but not with poor mental health. For females from countries with the highest gender inequality, there were significant regional differences in rates of assault, with SSA migrants experiencing high rates compared with those from SA. Relative to economic immigrants, refugees were at increased risk of sustaining assaults (IRR: 2.96, 95%CI: 2.32, 3.76) and poor mental health (IRR: 1.73, 95%CI: 1.50, 2.01). Higher educational attainment (bachelor’s degree or higher) at immigration was protective (assaults IRR: 0.64, 95%CI: 0.51, 0.80; poor mental health IRR: 0.69, 95% CI: 0.60, 0.80). Conclusion Source country gender inequality is not consistently associated with post-migration violence against women or severe depression, anxiety and self-harm in Ontario, Canada. Community-based research and intervention to address the documented socio-demographic disparities in outcomes of female immigrants is needed.

Abstract Background The purpose of this study was to investigate the relationship between breast density, age, and mammographic lesion type among Chinese breast cancer patients included in a large clinical dataset. Methods A review of mammographic images acquired between July 2014 and June 2017 from a total of 9716 retrospectively registered breast cancer patients was conducted. Mammographic breast density was defined according to the American College of Radiology Breast Imaging Reporting and Data System (ACR BI-RADS) 4-class density rating. Mammographic lesion types were defined according to the ACR BI-RADS, including mass, mass with calcifications, calcifications, architectural distortion/asymmetries, and architectural distortion/asymmetries with calcifications. Three experienced breast radiologists interpreted all mammograms. The chi-square (χ2) test and Pearson correlation analyses were performed to assess the relationship between breast density, age, and mammographic lesion type. Results A significant inverse relationship was observed between the BI-RADS breast density rating given by radiologists and patient age (r = − 0.521, p

Dual-ball-screw feed drive systems (DBSFDSs) are designed for most high-end manufacturing equipment. However, the mismatch between the dynamic characteristic parameters (e.g., stiffness and inertia) and the P-PI cascade control method reduces the accuracy of the DBSFDSs owing to the structural characteristic changes in the motion. Moreover, the parameters of the P-PI cascade controller of the DBSFDSs are always the same even though the two axes have different dynamic characteristics, and it is difficult to tune two-axis parameters simultaneously. A new application of the combination of the grey wolf optimization (GWO) algorithm and the P-PI cascade controller is presented to solve these problems and enhance the motion performance of DBSFDSs. The novelty is that the flexible coupling model and dynamic stiffness obtained from the motor current can better represent the two-axis coupling dynamic characteristics, and the GWO algorithm is used to adjust the P-PI controller parameters to address variations in the positions of the moving parts and reflect characteristic differences between the two axes. Comparison of simulation and experimental results validated the superiority of the proposed controller over existing ones in practical applications, showing a decrease in the tracking error of the tool center and non-synchronization error of over 34% and 39%, respectively.

Abstract Background Porcine Parvovirus (PPV) is a Parvovirinae virus that can cause embryonic and fetal loss and death and mummification in affected fetal pigs. Unlike conventional vaccines, virus-like particles (VLPs) inherit the natural structure of their authentic virions and highly immunostimulatory that can induce strong humoral immune and T cell responses with no risk of pathogenicity. The production of PPV VLPs is still a challenge based on traditional expression platforms due to their low yields and high culture costs. Kluyveromyces marxianus is a safe and fast-growing eukaryote that can get high biomass with low-cost cultures. In this study, we investigated the expression and downstream processes of PPV VLPs in K. marxianus, and the potential for effective stand-alone vaccines. Results After optimization according to the codon bias of K. marxianus, the VP2 protein from Kresse strain was highly expressed. In a 5 L fermentator, the yield of PPV VLPs reached 2.5 g/L, quantified by HPLC, using a defined mineral medium after 48 h fermentation. Two strategies were established to purify intracellular PPV VLPs: (i) Using the cation exchange chromatography coupled with Sephacryl® S-500 HR chromatography to purify VLPs from the supernatants of pH adjusted cell lysates. (ii) Using anion exchange chromatography followed by cross-flow diafiltration to recover the VLPs precipitated in pH adjusted cell lysates. The purity of PPV VLPs reached about 95%, and total recovery was more than 60%. Vaccination of mice with the purified PPV VLPs induced high titers of specific IgG antibodies in sera, and showed hemagglutination inhibitions on both swine and guinea pig erythrocytes. Spleen lymphocyte proliferation and cytokines detection suggested the PPV VLPs produced by K. marxianus provoked the cellular immune and humoral immunity responses in mice. Conclusions This is the highest production of recombinant PPV VLPs achieved to date. The superiorities, Generally Recognized As Safe (GRAS), high production, short lead time, and low cost, make K. marxianus a greatly competitive platform for bioproduction of PPV VLPs vaccine.

AIM: To investigate the clinical efficacy and safety of femtosecond laser-assisted steepest-meridian clear corneal incisions for correcting preexisting corneal astigmatism performed at the time of cataract surgery. METHODS: This prospective case series study comprised consecutive age-related cataract patients with corneal regular astigmatism (range: +0.75 to +2.50 D) who had femtosecond laser-assisted steepest-meridian clear corneal incisions (single or paired). Corneal astigmatism was performed with the Pentacam preoperatively and 3mo postoperatively. Total corneal astigmatism and steepest-meridian measured in the 3-mm central zone were used to guide the location, size and number of clear corneal incision. The vector analysis of astigmatic change was performed using the Alpins method. RESULTS: Totally 138 eyes of 138 patients were included. The mean preoperative corneal astigmatism was 1.31±0.41 D, and was significantly reduced to 0.69±0.34 D (equivalent to difference vector) after surgery (P

Scaffold protein Ste5 and associated kinases, including Ste11, Ste7, and Fus3, are core components of the mating pheromone pathway, which is required to induce a mating response. Orthologs of these proteins are widely present in fungi, but to which extent one protein can be replaced by its ortholog is less well understood. Here, interspecies complementation was carried out to evaluate the functional homology of Ste5 and associated kinases in Kluyveromyces lactis, K. marxianus, and Saccharomyces cerevisiae. These three species occupy important positions in the evolution of hemiascomycetes. Results indicated that Ste5 and associated kinases in K. lactis and K. marxianus could be functionally replaced by their orthologs to different extents. However, the extent of sequence identity, either between full-length proteins or between domains, did not necessarily indicate the extent of functional replaceability. For example, Ste5, the most unconserved protein in sequence, achieved the highest average functional replaceability. Notably, swapping Ste5 between K. lactis and K. marxianus significantly promoted mating in both species and the weakened interaction between the Ste5 and Ste7 might contribute to this phenotype. Consistently, chimeric Ste5 displaying a higher affinity for Ste7 decreased the mating efficiency, while chimeric Ste5 displaying a lower affinity for Ste7 improved the mating efficiency. Furthermore, the length of a negatively charged segment in the Ste7-binding domain of Ste5 was negatively correlated with the mating efficiency in K. lactis and K. marxianus. Extending the length of the segment in KlSte5 improved its interaction with Ste7 and that might contribute to the reduced mating efficiency. Our study suggested a novel role of Ste5-Ste7 interaction in the negative regulation of the pheromone pathway. Meanwhile, Ste5 mutants displaying improved mating efficiency facilitated the breeding and selection of Kluyveromyces strains for industrial applications.

Background and PurposeRapid eye movement (REM) Rapid eye movement sleep behavior disorder (RBD) is a common non-motor symptom of PD. However, the association between the SNCA rs3910105 genotype and RBD in Parkinson’s disease (PD) remains unclear.MethodsThis study used Parkinson’s Progression Markers Initiative (PPMI) data and included 270 patients with newly diagnosed PD without RBD who were divided into SNCA rs3910105 C carriers (CC+CT; n = 187) and TT carriers (n = 83). They were followed up for 5 years to identify the development of RBD. To investigate the influence of cerebrospinal fluid (CSF) alpha-synuclein (α-syn) and β-amyloid 1–42 (Aβ42) in the association between rs3910105 and RBD, the patients were additionally classified into “high-level” and “low-level” groups using cutoff values for CSF α-syn and Aβ42 levels.ResultsAt baseline, the rs3910105 C allele group had lower CSF α-syn and Aβ42 levels than the TT group. During the 5.0-year follow-up, the rs3910105 C allele group had a higher incidence of RBD than the TT group. In the subgroup analyses, the effect of the rs3910105 C allele was not found in the “low-level” group. However, in the “high-level” group, the rs3910105 C allele independently increased the risk of RBD.ConclusionThe SNCA rs3910105 C allele might be a novel genetic risk factor for RBD development in PD, α-syn pathways might have a role in this association and more basic research would be needed to elucidate the mechanism in the future.

BackgroundA number of studies have shown that E-test overestimated the presence of Helicobacter pylori resistance compared to agar dilution.ObjectiveThe purpose of this study was to explore whether E-test could be an alternative for agar dilution to detect the metronidazole susceptibility of H. pylori.MethodE-test and agar dilution were used to assess the susceptibility of H. pylori to metronidazole, clarithromycin, and levofloxacin in 281 clinical isolates obtained from China where the resistance was high. Cohen’s kappa analysis, McNemar’s test, and essential and categorical agreement analysis were performed for these two methods.ResultsOverall, the result of the E-test showed a similar prevalence of resistance rate to all antibiotics compared with agar dilution. The essential agreement of the E-test method and agar dilution in the evaluation susceptibility of H. pylori to clarithromycin and levofloxacin was moderate at 89.0 and 79.7%, respectively, but only 45.9% for metronidazole. The results shown by a categorical agreement (CA) between the E-test and agar dilution were 100% for both clarithromycin and levofloxacin. As for metronidazole, the CA was 98.7%, no major error was identified, and the rate of a very major error was 1.8%.ConclusionE-test can be an alternative method to detect the metronidazole susceptibility of H. pylori.

Host adaptation has the potential to cause rapid genetic variation in symbiotic microorganisms in insects. How mutations in symbiotic viruses favor viral fitness in hosts and even influence host adaptability to new environments remains elusive. Here, we explored the role of genetic divergence at one site of a symbiotic virus, Acyrthosiphon pisum virus (APV), in the host aphid’s adaptation to unfavorable plants. Based on the transcriptomes of the pea aphid Vicia faba colony and Vicia villosa colony, 46 single nucleotide polymorphism (SNP) sites were found in the APV genomes from the two aphid colonies. One SNP at site 5,990, G5990A, located at the RNA-dependent RNA polymerase (RdRp) domain, demonstrated a predominance from G to A when the host aphids were shifted from V. faba to the low-fitness plants V. villosa or Medicago sativa. This SNP resulted in a substitution from serine (S) to asparagine (N) at site 196 in RdRp. Although S196N was predicted to be located at a random coil far away from conserved functional motifs, the polymerase activity of the N196 type of RdRp was increased by 44.5% compared to that of the S196 type. The promoted enzymatic activity of RdRp was associated with a higher replication level of APV, which was beneficial for aphids as APV suppressed plant’s resistance reactions toward aphids. The findings showed a novel case in which mutations selected in a symbiotic virus may confer a favor on the host as the host adapts to new environmental conditions.

The meshing performance of enveloping tours worm drive requires the envelope lines to be matched strictly in accordance with the established relationship， the accuracy of tooth profile will directly affect its application performance. Aiming at the complicate meshing surface representation issue of cone-generated enveloping torus worm， the digital modeling method of this worm is proposed. The modeling frame is established firstly， and the meshing equations of the working tooth profile in different coordinate systems for the worm are deduced by applying differential geometry， kinematics， envelope theory and space coordinate transformation method， and the digital models of the working tooth profile of the worm are established， simultaneously， the generatrices equation of bottom and addendum surface are worked out. In addition， the constraint conditions of the worm digital models are constructed according to the enveloping process and boundary conditions of tooth profile. The solving algorithm for the complex nonlinear mathematical models is also designed based on the forming principle of the envelope surface， the instantaneous contact line and all meshing point cloud for the tooth profile are calculated， the distribution of contact line of worm tooth profile is also given. The digital solid model of worm is obtained by using curve and surface fitting technology based on the point cloud of worm tooth profile. The modeling experiment demonstrate that the digital model of worm is accurate， the designed solving algorithm of the model is effective as well as convergence， the worm tooth profile is of high precision， and the error of the worm tooth profile is at the level of 10-9. The research results can lay an accurate model foundation for precision digital manufacturing of cone-generated envelope torus worm and corresponding cone-generated double-envelope worm gear hob.

Background: Given the high mortality of bacterial bloodstream infections (BSI), blood culture results do not meet clinical needs timely due to being time-consuming and having low positive rate. Whether we can identify the severity and type of bacterial infections by cytokines is a controversial issue. Objective: To investigate the dynamic change of cytokines in BSI. Methods: 55 patients with Gram-positive (GP) BSI, 64 patients with Gram-negative (GN) BSI and 52 healthy controls were enrolled. We quantitatively detected the cytokines interleukin (IL)-2, IL-4, IL-6, IL-10, tumor necrosis factor-alpha (TNF-α) and interferon-gamma (IFN-γ) by flow cytometry in the sera. The levels of procalcitonin, C-reactive protein, leukocytes and neutrophils were also detected simultaneously. Results: There were significantly up-regulated IL-6 and IL-10 expression in BSI patients, particularly in the GN-BSI, for instance Escherichia coli and Klebsiella pneumoniae infections; following the treatment, IL-6 and IL-10 decreased by 10-23 and 4-27 times, respectively. Additionally, IL-2, TNF-α and IFN-γ expression increased slightly in BSI patients and IFN-γ expression declined as GN-BSI progressed. Conclusion: IL-6 and IL-10 are closely associated with the severity and treatment efficacy of BSI, and can help to distinguish between GP-BSI and GN-BSI at an early stage.

The search for magnetic Weyl fermion remains a challenge. Here, the authors report angle-resolved photoemission spectroscopy and magnetotransport measurements resolving the topological properties of Weyl fermion quasiparticles in magnetic non-centrosymmetric crystal PrAlGe.

Abstract Background Haemorrhoids occur commonly and frequently in the human digestive system. There are diverse causes of haemorrhoids and their in-depth pathogenesis is still currently unclear. Methods In this study, we explored haemorrhoids from an epigenetics perspective by employing RNA-Seq for comprehensive and in-depth analysis of the differences in microRNA (miRNA) transcripts between haemorrhoidal tissue and normal tissue in 48 patients with Grade II and above haemorrhoids. Results The results showed that 9 miRNAs were significantly upregulated (ratio > 3.5 and P-value 0.6 and P-value

Purpose: We investigated the inhibitory effect of bisphosphonates (BPs) on the crystallization of calcium oxalate monohydrate (COM), calcium phosphate (CaP), and magnesium ammonium phosphate (MAP) in synthetic urine, aiming to see 1) which specific BPs work best on a particular type of crystal and 2) what is the lowest concentration of BPs that inhibits crystal formation. Materials and Methods: Crystals from synthetic urine were exposed to different concentrations of BPs. Urinary turbidity was used as a marker of crystallization and was measured by spectrophotometry by use of a validated method in our laboratory. The percent inhibitory activity (IA) was calculated by using the formula: (a−b )/a×100, where a is baseline maximal turbidity and b is maximal turbidity with various concentrations of medication. Potassium citrate and magnesium citrate were used as positive controls. Results: At the lowest dose of 0.001 mg/mL, risedronate induced the highest IA of 37% on CaP, whereas ibandronate had the strongest IA on COM (24%). To initiate the inhibition of MAP crystallization, risedronate required a two-fold higher concentration (0.002 mg/mL) to reach 30% IA, whereas etidronate required a four-fold higher concentration (0.004 mg/mL) to reach 42% IA. Conclusions: BPs are good inhibitors of crystallization in synthetic urine, with risedronate and ibandronate being the most potent. At a low clinically acceptable dose, their highest inhibitory action was on CaP and COM crystals. Higher doses were needed to prevent MAP crystallization. Further investigation of the use of BPs in kidney stone prevention is warranted.

The molecular mechanisms underpinning how fasting inhibits tumourigenesis are not completely elucidated. Here, the authors show that fasting upregulates the cholesterogenic gene FDFT1 which leads to decreased AKT/mTOR/HIF1a signalling and glycolysis reduction in colorectal cancer.

Abstracts Background There have been reports of Helicobacter pylori (H. pylori) in the oral cavity and it has been suggested that the oral cavity may be a reservoir for H. pylori reflux from the stomach. High-throughput sequencing was used to assess the structure and composition of oral microbiota communities in individuals with or without confirmed H. pylori infection. Methods Saliva samples were obtained from 34 H. pylori infected and 24 H. pylori uninfected subjects. Bacterial genomic DNA was extracted and examined by sequencing by amplification of the 16S rDNA V3-V4 hypervariable regions followed by bioinformatics analysis. Saliva sampling was repeated from 22 of the 34 H. pylori infected subjects 2 months after H. pylori eradication. Results High-quality sequences (2,812,659) clustered into 95,812 operational taxonomic units (OTUs; 97% identity). H. pylori was detected in the oral cavity in infected (12/34), uninfected (11/24) and eradicated (15/22) subjects by technique of high-throughput sequencing, occupying 0.0139% of the total sequences. Alpha diversity of H. pylori infected subjects was similar to that of uninfected subjects (Shannon: 1417.58 vs. 1393.60, p > 0.05, ACE: 1491.22 vs. 1465.97, p > 0.05, Chao 1: 1417.58 vs. 1393.60, p > 0.05, t-test). Eradication treatment decreased salivary bacterial diversity (Shannon, p = 0.015, ACE, p = 0.003, Chao 1, p = 0.002, t-test). Beta diversity analysis based on unweighted UniFrac distances showed that the salivary microbial community structure differed between H. pylori infected and uninfected subjects (PERMANOVAR, pseudo-F: 1.49, p = 0.033), as well as before and after H. pylori eradication (PERMANOVAR, pseudo-F: 3.34, p = 0.001). Using LEfSe analysis, 16 differentially abundant genera were defined between infected and uninfected subjects, 12 of which had a further alteration after successful eradication. Conclusions Our study using high-throughput sequencing showed that H. pylori was present commonly in the oral cavity with no clear relation to H. pylori infection of the stomach. Both H. pylori infection and eradication therapy caused alterations in community and structure of the oral microbiota. Trial registration clinicaltrials.gov, NCT03730766. Registered 2 Nov 2018 - Retrospectively registered, https://clinicaltrials.gov/ct2/show/ NCT03730766.

Community detection is a critical issue in the field of complex networks. Recently, the nonnegative matrix factorization (NMF) method has successfully uncovered the community structure in the complex networks. However, this method has a significant drawback; most of community detection methods using NMF require the number of communities to be preassigned or determined the number of communities by searching for the best community structure among all candidates. To address this problem, in this paper, we use density peak clustering (DPC) to obtain the number of centers as the pre-defined parameter for nonnegative matrix factorization. However, due to sparse and high dimensional characteristics of complex networks, DPC cannot be used to detect community directly. To overcome this issue, we employ degree and hop of nodes as the density and distance indexes, respectively; we use NMF and Symmetric NMF to deal with linearly separable data and non-linearly separable data, respectively. Experimental results show that the proposed methods exhibit excellent performance on artificial and real-world networks and superior to the state-of-the-art methods which are the most common method for community detection of complex networks.

In this article, we consider two classes of $p$ -ary linear codes. This article is a generalization of the recent construction methods given by Jian, Lin and Feng (2019). By choosing different defining sets, two classes of two-weight or three-weight linear codes over finite fields are constructed and their weight distributions are determined based on Weil sums. We also give some examples and some of the linear codes are almost optimal with respect to the Griesmer bound which can be directly employed to obtain democratic secret sharing schemes. Additionally, all nonzero codewords are minimal and they are crucial to apply in association schemes, strongly regular graphs, weakly regular plateaued functions and authentication codes.

Oxaliplatin (OXA) is a third-generation platinum compound with clinical activity in multiple solid tumors. Due to the repetition of chemotherapy cycle, OXA-induced chronic neuropathy presenting as paresthesia and pain. This study explored the neuropathy of chemotherapy pain and investigated the analgesic effect of 2-bromopalmitate (2-BP) on the pain behavior of OXA-induced rats. The chemotherapy pain rat model was established by the five consecutive administration of OXA (intraperitoneal, 4 mg/kg). After the establishment of OXA-induced rats, the pain behavior test, inflammatory signal analysis and mitochondrial function measurement were conducted. OXA-induced rats exhibited mechanical allodynia and spinal inflammatory infiltration. Our fluorescence and western blot analysis revealed spinal astrocytes were activated in OXA rats with up-regulation of astrocytic markers. In addition, NOD-, LRR- and pyrin domain-containing 3 (NLRP3) inflammasome mediated inflammatory signal cascade was also activated. Inflammation was triggered by dysfunctional mitochondria which represented by increase in cyclooxygenase-2 (COX-2) level and manganese superoxide dismutase (Mn-SOD) activity. Intrathecally injection of 2-BP significantly attenuated dynamin-related protein 1 (Drp1) mediated mitochondrial fission, recovered mitochondrial function, suppressed NLRP3 inflammasome cascade, and consequently decreased mechanical pain sensitivity. For cell research, 2-BP treatment significantly reversed tumor necrosis factor-α (TNF-α) induced mitochondria membrane potential deficiency and high reactive oxygen species (ROS) level. These findings indicate 2-BP decreases spinal inflammation and relieves OXA-induced neuropathic pain via reducing Drp1-mediated mitochondrial dysfunction.

BackgroundCurrently, in Canada, existing health administrative data and hospital-inputted portal systems are used to measure the wait times to receiving a procedure or therapy after a specialist visit. However, due to missing and inconsistent labelling, estimating the wait time prior to seeing a specialist physician requires costly manual coding to label primary care referral notes.MethodsIn this work, we represent the notes using word-count vectors and develop a logistic regression machine learning model to automatically label the target specialist physician from a primary care referral note. These labels are not available in the administrative system. We also study the effects of note length (measured in number of tokens) and dataset size (measured in number of notes per target specialty) on model performance to help other researchers determine if such an approach may be feasible for them. We then calculate the wait time by linking the specialist type from a primary care referral to a full consultation visit held in Ontario, Canada health administrative data.ResultsFor many target specialties, we can reliably (F1Score ≥ 0.70) predict the target specialist type. Doing so enables the automated measurement of wait time from family physician referral to specialist physician visit. Of the six specialties with wait times estimated using both 2008 and 2015 data, two had a substantial increase (defined as a change such that the original value lay outside the 95% confidence interval) in both median and 75th percentile wait times, one had a substantial decrease in both median and 75th percentile wait times, and three has non-substantial increases.ConclusionsAutomating these wait time measurements, which had previously been too time consuming and costly to evaluate at a population level, can be useful for health policy researchers studying the effects of policy decisions on patient access to care.

The bar-headed goose (Anser indicus) has two black spots on its head. It is considered an important bird in China. It breeds in plateau lakes, especially saltwater lakes, and swamp areas. However, the intestinal flora of wild bar-headed geese in the Tibet Autonomous Region is currently not known. In this study, 16S rDNA sequencing was performed on the intestinal microbes of wild bar-headed geese. A total of 513,505 reads of raw data were obtained, and the results analyzed the average number of 128,376 ± 2,392 reads per sample. The microbiota of all samples consists of 10 main bacterial phyla, including Firmicutes, Proteobacteria, Bacteroidetes, Actinobacteria, Cyanobacteria, Patescibacteria, Deferribacteres, Planctomy-cetes, Fusobacteria, and Tenericutes. The results indicated that Firmicutes (67.34%) was the predominant phylum, followed by Proteobacteria (29.03%) and Cyanobacteria (1.97%). In our research, we identified the intestinal flora of the wild bar-headed goose, which provides valuable information for further research on the gene function of the bar-headed goose and the intestinal flora of wild animals. These findings are also useful and valuable for genetic and high-altitude research in the Tibet Autonomous Region.

Kluyveromyces marxianus is the fastest-growing eukaryote and a promising host for producing bioethanol and heterologous proteins. To perform a laboratory evolution of thermal tolerance in K. marxianus, diploid, triploid and tetraploid strains were constructed, respectively. Considering the genetic diversity caused by genetic recombination in meiosis, we established an iterative cycle of “diploid/polyploid - meiosis - selection of spores at high temperature” to screen thermotolerant strains. Results showed that the evolution of thermal tolerance in diploid strain was more efficient than that in triploid and tetraploid strains. The thermal tolerance of the progenies of diploid and triploid strains after a two-round screen was significantly improved than that after a one-round screen, while the thermal tolerance of the progenies after the one-round screen was better than that of the initial strain. After a two-round screen, the maximum tolerable temperature of Dip2-8, a progeny of diploid strain, was 3°C higher than that of the original strain. Whole-genome sequencing revealed nonsense mutations of PSR1 and PDE2 in the thermotolerant progenies. Deletion of either PSR1 or PDE2 in the original strain improved thermotolerance and two deletions displayed additive effects, suggesting PSR1 and PDE2 negatively regulated the thermotolerance of K. marxianus in parallel pathways. Therefore, the iterative cycle of “meiosis - spore screening” developed in this study provides an efficient way to perform the laboratory evolution of heat resistance in yeast.

Two major solar eruptions on AR 12673 produced a Forbush decrease (FD) event (reduction of cosmic rays) on 2017 September 8 and ground-level enhancement (GLE; enhancement of cosmic rays) on 2017 September 10. The occurrence of two contrasting cosmic-ray events within 2 days that are associated with two similar X-class solar flares (X9.3 and X8.2) and share the same active region on the Sun provides us a rare opportunity to understand the dominant factors in determining the properties of transient cosmic-ray events. Using a suite of modern-day instruments continuously tracking solar eruptions from the Sun to the Earth with ground-based cosmic-ray detectors, we reveal the complete cause–effect chain of activities for these two events. We conclude that the different consequences on the ground arise from two effects of the eruptions near the Sun: (1) the geometric effect of CMEs and (2) the intensity effect of CME-driven shocks. The first eruption, which originated at the heliographic longitude of W34° on 2017 September 6, had its CME ejecta and CME-driven shock intercept the Earth, leading to the FD event. The second eruption, which occurred on September 10 at W88°, only had its far flank reach the Earth. The peak shock speed of 3344 km s ^−1 of the second eruption, much faster than the 2175 km s ^−1 of the first eruption, is the dominant factor producing the GLE event, even though the first eruption is better connected magnetically to the Earth and has a similar flare. The results indicate that the production of GLE particles can be dominated by fast-enough CME-driven shocks.

Previous studies have demonstrated an association between short-term exposure to ambient temperature and mortality. However, the long-term effects of elevated temperature and temperature variability on mortality have remained somewhat elusive in epidemiological studies. We conducted a comprehensive epidemiological study utilizing Chinese population census data from 2000 and 2010. Census-derived demographic and socioeconomic factors were paired with temperature data from the European Re-Analysis Land Dataset across 2823 counties. We employed a difference-in-difference approach to quantitatively examine the relationship between all-cause mortality and annual exposure to mean temperature and diurnal temperature range (DTR). Additionally, we evaluated the potential effects of socioeconomic and environmental covariate modifications on this relationship and calculated the attributable mortality. Lastly, we projected excess deaths attributable to annual temperature exposure under various shared socioeconomic pathways (SSPs, e.g. SSP126, SSP370, and SSP585). For each 1 °C rise in annual mean temperature and DTR, the mortality risk could increase by 6.12% (95% CI: 0.84%, 11.69%) and 7.72% (95% CI: 3.75%, 11.84%), respectively. Counties with high labor-force ratios and high NO _2 and O _3 concentrations appeared to be sensitive to the annual mean temperature and DTR. Climate warming from 2000 to 2010 may have resulted in 5.85 and 14.46 additional deaths per 10 000 people attributable to changes in annual mean temperature and DTR, respectively. The excess mortality related to changes in annual mean temperature and DTR is expected to increase in the future, with special attention warranted for long-term temperature changes in Southwest China. Our findings indicate that long-term mean temperature and DTR could significantly impact mortality rates. Given the spatial heterogeneity of increased mortality risk, the formulation of region-specific strategies to tackle climate change is crucial.

We, the Editors, Authors and Publisher of the journal Artificial Cells, Nanomedicine, and Biotechnology, have retracted the following article:Tao Peng, Xiaoyan Liu, Jingtao Wang, Yu Liu, Zhenqiang Fu, Xingrong Ma, Junmin Li, Guifang Sun, Yangfei Ji, Jingjing Lu, Wencui Wan & Hong Lu (2019) Long noncoding RNA HAGLROS regulates apoptosis and autophagy in Parkinson’s disease via regulating miR-100/ATG10 axis and PI3K/Akt/mTOR pathway activation. Artificial Cells, Nanomedicine, and Biotechnology, 47:1, 2764–2774, DOI: 10.1080/21691401.2019.1636805Since publication, the authors continued their study and found that the original experimental results were unverifiable. The authors checked their data and confirmed there are fundamental errors present. Therefore, they have agreed to the retraction of this article. The authors apologise for this oversight.We have been informed in our decision-making by our policy on publishing ethics and integrity and the COPE guidelines on retractions.The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as ‘Retracted’.

Abstract Background Identification of imaging traits to discriminate clinically significant prostate cancer is challenging due to the multi focal nature of the disease. The difficulty in obtaining a consensus by the Prostate Imaging and Data Systems (PI-RADS) scores coupled with disagreements in interpreting multi-parametric Magnetic Resonance Imaging (mpMRI) has resulted in increased variability in reporting findings and evaluating the utility of this imaging modality in detecting clinically significant prostate cancer. This study assess the ability of radiological traits (semantics) observed on multi-parametric Magnetic Resonance images (mpMRI) to discriminate clinically significant prostate cancer. Methods We obtained multi-parametric MRI studies from 103 prostate cancer patients with 167 targeted biopsies from a single institution. The study was approved by our Institutional Review Board (IRB) for retrospective analysis. The biopsy location had been identified and marked by a clinical radiologist for targeted biopsy based on initial study interpretation. Using the target locations, two study radiologists independently re-evaluated the scans and scored 16 semantic traits on a point scale (up to 5 levels) based on mpMRI images. The semantic traits describe size, shape, and border characteristics of the prostate lesion, as well as presence of disease around lymph nodes (lymphadenopathy). We built a linear classifier model on these semantic traits and related to pathological outcome to identify clinically significant tumors (Gleason Score ≥ 7). The discriminatory ability of the predictors was tested using cross validation method randomly repeated and ensemble values were reported. We then compared the performance of semantic predictors with the PI-RADS predictors. Results We found several semantic features individually discriminated high grade Gleason score (ADC-intensity, Homogeneity, early-enhancement, T2-intensity and extraprostatic extention), these univariate predictors had an average area under the receiver operator characteristics (AUROC) ranging from 0.54 to 0.68. Multivariable semantic predictors with three features (ADC-intensity; T2-intensity, enhancement homogenicity) had an average AUROC of 0.7 [0.43, 0.94]. The PI-RADS based predictor had average AUROC of 0.6 [0.47, 0.75]. Conclusion We find semantics traits are related to pathological findings with relatively higher reproducibility between radiologists. Multivariable predictors formed on these traits shows higher discriminatory ability compared to PI-RADS scores.