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Abstract Background Genomic structural variations (GSVs), notably copy number variations (CNVs), significantly shape genetic diversity and facilitate adaptation in cattle populations. Despite their importance, the genome-wide characterization of CNVs in indigenous Ethiopian cattle breeds—Abigar, Fellata, and Gojjam-Highland remains largely unexplored. In this study, we applied a read-depth approach to whole genome sequencing (WGS) data to conduct the first comprehensive analysis of CNVs in these populations. Results We identified 3,893 CNV regions (CNVRs) covering 19.15 Mb (0.71% of the cattle genome). These CNVRs ranged from 1.60 kb to 488.0 kb, with an average size of 4.92 kb. These CNVRs included deletions (1713), duplications (1929), and mixed events (251) showing notable differences in distribution among the breeds. Four out of five randomly selected CNVRs were successfully validated using real time polymerase chain reaction (qPCR). Further analyses identified candidate genes associated with high-altitude adaptation (GBE1 and SOD1), heat stress adaptation (HSPA13, DNAJC18, and DNAJC8) and resistance to tick infestations (BoLA and KRT33A). In addition, variance stabilizing transformation (V ST ) statistics highlighted population-specific CNVRs, emphasizing the unique genetic signatures of high-altitude adaptation in the Gojjam-Highland cattle breed. Among the detected CNVRs, 4.93% (192 out of 3,893) overlapped with 520 quantitative traits loci (QTLs) associated with six economically important trait categories suggesting that these CNVRs may significantly contribute to the genetic variation underlying these traits. Conclusions Our comprehensive analysis reveals significant CNVRs associated with key adaptive traits in Ethiopian cattle breeds highlighting their genetic diversity and resilience. These findings offer valuable insights into the genetic basis of adaptability and can inform sustainable breeding practices and conservation efforts. Future research should prioritize the functional validation of these CNVRs and their integration into breeding programs to enhance traits such as disease resistance and environmental adaptability.

Abstract Indigenous animal genetic resources play a crucial role in preserving global genetic diversity and supporting the livelihoods of millions of people. In Ethiopia, the majority of the cattle population consists of indigenous breeds. Understanding the genetic architecture of these cattle breeds is essential for effective management and conservation efforts. In this study, we sequenced DNA samples from 70 animals from seven indigenous cattle breeds, generating about two terabytes of pair-end reads with an average coverage of 14X. The sequencing data were pre-processed and mapped to the cattle reference genome (ARS-UCD1.2) with an alignment rate of 99.2%. Finally, the variant calling process produced approximately 35 million high-quality SNPs. These data provide a deeper understanding of the genetic landscape, facilitate the identification of causal mutations, and enable the exploration of evolutionary patterns to assist cattle improvement and sustainable utilization, particularly in the face of unpredictable climate changes.

Abstract Objective The relationship between systemic immune‐inflammation index (SII) and psoriasis and its prognosis is not yet clear. In this study, the correlation between SII and psoriasis, psoriasis comorbidities, and all‐cause mortality was investigated based on the National Health and Nutrition Examination Survey (NHANES). Methods The study population was derived from five NHANES cycles: 2003–2006, 2009–2014, and survival follow‐up was as of December 31, 2019. The association between SII and psoriasis and its comorbidities was analyzed using weighted multivariate logistic regression models. Weighted COX regression was used to calculate hazard ratios (HRs) and the corresponding 95% confidence intervals (CIs). Restricted cubic spline, subgroup and sensitivity analyses were also used. Logarithmic conversion was performed on SII(log2SII) to reduce the impact of outliers. Results A total of 21,431 participants were included in this study. As a continuous variable, log2SII was significantly associated with psoriasis in the fully adjusted model [OR = 1.20(1.04–1.39), p = .01]. log2SII remained positively associated with psoriasis after excluding participants with a history of cancer or cardiovascular disease (CVD), or non‐Hispanic black participants. Among psoriasis patients, log2SII was significantly associated with metabolic syndrome (MetS) [OR = 1.68(1.19,2.38), p = .004] and all‐cause mortality [HR = 1.48(1.09,1.99), p = .01]. Similar results were consistently observed when SII was analyzed as a categorical variable (in quartiles). Conclusion This study suggested a positive association between SII and the prevalence of psoriasis. Among psoriasis patients, SII was positively correlated with MetS and all‐cause mortality.

The aim of this meta-analysis was to investigate the effect of technology-based interventions on mathematical word problem solving for students with disabilities. This study also assessed the quality of research based on What Works Clearinghouse (WWC) design standards. A total of 21 studies were included in the analysis. This study computed an overall effect and analyzed moderators of group design studies (Hedges’ g) and single-case design studies (between-case standardized mean difference) in the same analyses. The results show that the overall effect of technology-based interventions on word problems across 21 studies was large (Hedges’ g = 1.18, 95% CI = 0.84, 1.52). Additionally, the studies meeting WWC design standards demonstrated significantly greater effects. The moderator analyses indicated that certain study characteristics, such as publication years, settings, intervention agents, technology devices and types, and mathematics topics moderated the effects of interventions. The four studies that evaluated the generalization effect of the intervention using distal standardized assessments showed a near moderate effect (Hedges’ g = 0.49, 95% CI = 0.09, 0.9). Implications for future research and practice are discussed.

BackgroundOutside of pregnancy, intuitive eating (IE) is associated with lower body weight, blood glucose, and higher positive mood. However, little was known about the relationship between IE and anxiety-depression in the GDM population. Thus, this study aimed to investigate the association of IE with anxiety and depression, pregnancy weight and pregnancy blood glucose in the first and second GDM visit.MethodsData from 310 pregnant women with GDM from the Fujian Maternal and Child Health Hospital Trial (Approval Number: 2020Y9133) were analyzed. IE was assessed using the Intuitive Eating Scale-2 subscales of Eating for Physiological Reasons rather than Emotional Reasons (EPR), Relying on Hunger and Satiety Cues (RHSC) and Body-Food Choice Consistency (B-FCC). Observations included weight, body mass index (BMI), fasting plasma glucose (FPG) and 2-h postprandial blood glucose; the Hospital Anxiety and Depression Scale (HADS) was used to assess the level of anxiety and depression in pregnant women with GDM. Linear regression analysis was used to assess the correlation between IE and anxiety, depression, pregnancy blood glucose and weight.ResultsThe cross-sectional analysis showed that the EPR eating behavior was negatively correlated with anxiety and depression, and the B-FCC eating behavior was negatively correlated with depression at both the first and second GDM visit; in addition, the B-FCC eating behavior was associated with lower BMI in the third trimester (all p

Introduction: Honey bees provides valuable pollination services for world food crops and wild flowering plants which are habitats of many animal species and remove carbon dioxide from the atmosphere, a powerful tool in the fight against climate change. Nevertheless, the honey bee population has been declining and the majority of colony losses occur during the winter. Objectives: The goal of this study was to understand the mechanisms underlying overwinter colony losses and develop novel therapeutic strategies for improving bee health. Methods: First, pathogen prevalence in overwintering bees were screened between 2015 and 2018. Second, RNA sequencing (RNA-Seq) for transcriptional profiling of overwintering honey bees was conducted and qRT-PCR was performed to confirm the results of the differential expression of selected genes. Lastly, laboratory bioassays were conducted to measure the effects of cold challenges on bee survivorship and stress responses and to assess the effect of a novel medication for alleviating cold stress in honey bees. Results: We identified that sirtuin signaling pathway is the most significantly enriched pathway among the down-regulated differentially expressed genes (DEGs) in overwintering diseased bees. Moreover, we showed that the expression of SIRT1 gene, a major sirtuin that regulates energy and immune metabolism, was significantly downregulated in bees merely exposed to cold challenges, linking cold stress with altered gene expression of SIRT1. Furthermore, we demonstrated that activation of SIRT1 gene expression by SRT1720, an activator of SIRT1 expression, could improve the physiology and extend the lifespan of cold-stressed bees. Conclusion: Our study suggests that increased energy consumption of overwintering bees for maintaining hive temperature reduces the allocation of energy toward immune functions, thus making the overwintering bees more susceptible to disease infections and leading to high winter colony losses. The novel information gained from this study provides a promising avenue for the development of therapeutic strategies for mitigating colony losses, both overwinter and annually.

Abstract Background Limited diagnostic capabilities, resources and health worker skills have deterred the advancement of birth defects surveillance systems in most low- and middle-income countries (LMICs). Empowering health workers to identify and diagnose major external birth defects (BDs) is crucial to establishing effective hospital-based BD surveillance. Makerere University-Johns Hopkins University (MU-JHU) Research Collaboration BD Surveillance System consists of three diagnostic levels: (1) surveillance midwives, (2) MU-JHU clinical team, and (3) U.S. Centers for Disease Control and Prevention (CDC) birth defects subject matter experts (SMEs) who provide confirmatory diagnosis. The diagnostic concordance of major external BDs by surveillance midwives or MU-JHU clinical team with CDC birth defects SMEs were estimated. Methods Study staff went through a series of trainings, including birth defects identification and confirmation, before surveillance activities were implemented. To assess the diagnostic concordance, we analyzed surveillance data from 2015 to 2021 for major external BDs: anencephaly, iniencephaly, encephalocele, spina bifida, craniorachischisis, microcephaly, anophthalmia/microphthalmia, anotia/microtia, cleft palate alone, cleft lip alone, cleft lip with cleft palate, imperforate anus, hypospadias, talipes equinovarus, limb reduction, gastroschisis, and omphalocele. Positive predictive value (PPV) as the proportion of BDs diagnosed by surveillance midwives or MU-JHU clinical team that were confirmed by CDC birth defects SMEs was computed. PPVs between 2015 and 2018 and 2019–2021 were compared to assess the accuracy of case diagnosis over time. Results Of the 204,332 infants examined during 2015–2021, 870 infants had a BD. Among the 1,245 BDs identified, 1,232 (99.0%) were confirmed by CDC birth defects SMEs. For surveillance midwives, PPV for 7 of 17 BDs was > 80%. For the MU-JHU clinical team, PPV for 13 of 17 BDs was > 80%. Among surveillance midwives, PPV improved significantly from 2015 to 2018 to 2019–2021, for microcephaly (+ 50.0%), cleft lip with cleft palate (+ 17.0%), imperforate anus (+ 30.0%), and talipes equinovarus (+ 10.8%). Improvements in PPV were also observed among MU-JHU clinical team; however, none were significant. Conclusion The diagnostic accuracy of the midwives and clinical team increased, highlighting that BD surveillance, by front-line health care workers (midwives) in LMICs is possible when midwives receive comprehensive training, technical support, funding and continuous professional development.

Summary: Recent studies have revealed cellular heterogeneity of mesenchymal stromal cells and immune cells in adipose tissue and emphasized the need for quantitative analysis of small numbers of functionally distinct cells using state-of-the-art “omics” technologies. Here, we present an optimized protocol for precise protein quantification from minute amounts of samples. We describe steps for isolation of mouse adipose progenitor cells, proteomics sample preparation, mass spectrometry measurement, and computational analysis. This protocol can be adapted to other samples with limited amounts.For complete details on the use and execution of this protocol, please refer to Shan et al. (2022).1 : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

Objective This study explored whether plant-based and animal-based dietary patterns are associated with plasma glucose levels during oral glucose tolerance test in women with gestational diabetes mellitus (GDM).Design A prospective cohort study was conducted using a Food Frequency Questionnaire to collect dietary data. Dietary patterns were derived using principal component analysis. Multivariate logistic regression analysis was performed to explore the association between dietary patterns and plasma glucose levels. Stratified analyses were conducted according to maternal age, prepregnancy body mass index (BMI) and other confounders.Setting and participants The study, conducted in January 2022 in two hospitals in Fujian, China, involved 424 women diagnosed with GDM using a 75 g 2-hour oral glucose tolerance test at 24–28 gestational weeks.Results Six maternal dietary patterns (plant based and animal based) were identified. Participants with plant-based pattern had lower 2-hour plasma glucose levels than those with animal-based pattern (β=−0.314; 95% CI (−0.596 to –0.032)). After adjusting the regression model covariates, this significant association remained (β=−0.288; 95% CI (−0.568 to –0.008)) and appeared more pronounced in women aged 30 years or above and those with prepregnancy BMI

Objective: The research is to explore the enzyme inhibition of Perilla crude extract, and to preliminarily elucidate the pharmacological substance basis of them on hyperglycemia, hyperuric acid and hyperlipidemia. Methods: The content of flavonoids and phenolic acid in UV extract was determined and showed the active components associated with enzyme inhibition. In vitro experiments, the inhibition of Perilla extracts on different enzyme activity was determined and the inhibitory activity was evaluated by IC50. Molecular docking was used to predict the targets of Perilla crude extract on pancreatic lipase and amylase inhibition. Results: Flavone content in the crude UV extract was 0.309 8 mg/mg, and the total phenolic acid content was 58.59 mg/g. The IC50 values of Perilla crude extractd for α-amylase, xanthine oxidase, pancreatic lipase and acetylcholinesterase were 0.273, 0.244, 0.347 and 0.018 mg/mL, respectively.Apigenin-5-O-β-D-glucosine, xyrhinin-7-diglucosotide, apigenin-7-glucosine, cannol-3-O-ruassin, rosemary acid, rutin and others were the effective active components of perilla crude extracts. Conclusion: The Perilla crude extracts all have certain inhibitory activities on four enzymes, and presents a dose-effect relationship.

This study investigated the impact of visual cueing on attention guidance, deep-thinking promotion, and performance optimization in arithmetic word problem solving for students with mathematical learning difficulties (MLD). The participants included eight students with MLD and twenty students without MLD who attempted to solve mathematical word problems with and without visual cueing. Eye movements were recorded during the tasks. A repeated-measure design and nonparametric tests were applied to enhance the statistical power of the study. The data analysis results indicated that visual cueing effectively guided and sustained the attention of students with MLD, reducing their off-task duration. However, it showed limited influence in facilitating deep thinking and performance improvement for these students. There were no significant attention-guidance or performance-improvement effects observed in the problem-solving processes of students without MLD, who initially demonstrated better concentration levels and performance. The potential explanations for these findings are further discussed in this paper.

Purpose To identify more accurate predictors of upper urinary tract dilatation (UUTD) in neurogenic bladder (NB) children, we studied the relationship among urodynamic parameters at different bladder filling stages, detrusor leak point pressure (DLPP) and UUTD. Methods A total of 158 children (3–16 years) with NB were included and then divided into 2 groups according to whether their NB diagnosis was complicated with UUTD: the UUTD group (39 patients) and those without UUTD group (control group, 119 patients). The bladder filling phase was divided into 3 equal parts: the early, middle, and end filling stages. The bladder compliance (BC) and detrusor pressure (△Pdet) at each phase and DLPP at the end filling stage were recorded. Results A BC8 cm H2O in the early stage, 20 cm H2O in the middle stage and 25 cm H2O in the end stage are more sensitive than △Pdet >40 cm H2O in the end stage (82%, 85%, 85%, vs. 49%). A DLPP cutoff value of 20 cm H2O showed higher sensitivity for predicting UUTD than 40 cm H2O. Conclusions Low BC and a high △Pdet in the middle and end filling stages are more accurate factors than classic indicators for predicting UUTD. In addition, a DLPP value of >20 cm H2O in the end bladder filling stage shows high sensitivity.

Abstract Background Pregnant women in Shanghai have long been at risk for mild iodine deficiency. Because thyroid autoimmunity in pregnant women can lead to premature birth and miscarriage as well as neurodevelopmental deficits in the fetus, the aim of this study was to explore the association of iodine nutrition status with thyroid antibodies during pregnancy. Methods A pregnancy-birth cohort was conducted including 4635 pregnant women in Shanghai, China. The eligible participants underwent a face-to-face interview and completed questionnaire surveys to collect baseline information and diet intake. Spot urine samples were collected to test urine iodine. Thyroid antibodies including thyroid peroxidase antibodies (TPOAb), thyroglobulin antibodies (TgAb) and thyrotrophic antibodies (TRAb) were tested. Single-factor analysis and logistic regression were used to evaluate the association between iodine status and thyroid autoimmunity during pregnancy. Results The median urinary iodine excretion level in the sample was 138.14 μg/L (interquartile range [IQR] 80.90–219.00 μg/L). Among all the subjects, 25.9% consumed non-iodized salt, 54.5% had iodine deficiency, and 31.0% had thyroid autoimmunity. The proportion of patients with iodine deficiency was significantly higher among those who consumed non-iodized salt (36.9% vs. 33.1%; p = 0.04). After adjusting for age, educational status, former smoker status, former drinker status, first pregnancy, and previous thyroid disease, non-iodized salt (odds ratio [OR] = 1.394 [confidence interval, CI, 1.165–1.562]; p = 0.003), iodine-rich food (OR = 0.681 [CI 0.585–0.793]; p = 0.003), iodized nutritional supplements (OR = 0.427 [CI 0.347–0.526]; p = 0.003), were found to be individually associated with thyroid autoimmunity in all participants. The results of the multivariable restricted cubic spline regression analysis showed a non-linear relationship between the continuous change in iodine intake and thyroid autoimmunity (p = 0.019). Participants with iodine deficiency (urinary iodine concentration, UIC,

Abstract An overreliance on commercial, kit-based RNA extraction in the molecular diagnoses of infectious disease presents a challenge in the event of supply chain disruptions and can potentially hinder testing capacity in times of need. In this study, we adapted a well-established, robust TRIzol-based RNA extraction protocol into a high-throughput format through miniaturization and automation. The workflow was validated by RT-qPCR assay for SARS-CoV-2 detection to illustrate its scalability without interference to downstream diagnostic sensitivity and accuracy. This semi-automated, kit-free approach offers a versatile alternative to prevailing integrated solid-phase RNA extraction proprietary systems, with the added advantage of improved cost-effectiveness for high volume acquisition of quality RNA whether for use in clinical diagnoses or for diverse molecular applications.

The interaction between plants and microbes dominates plant growth and fitness in specific environments. The study of the relationship between plant genotypes and rhizobacterial community structure would provide a deep insight into the recruitment strategies of plants toward soil bacteria. In this study, three genotypes of 18-year-old mature poplar (H1, H2, and H3) derived from four different parents were selected from a germplasm nursery of Populus deltoides. Rhizosphere soil carbon, nitrogen, and phosphorus properties as well as the 16S rDNA sequences of rhizobacterial communities were analyzed to determine the relationship between poplar genotypes and rhizobacterial communities assembly. The results showed there were significant differences in the diversity (Chao1, ACE index, and Shannon index) of rhizobacterial communities between H1 and H2, as well as between H2 and H3, but no difference between H1 and H3. Principal component analysis also revealed a similar structure of rhizobacterial communities between H1 and H3, whereas the rhizobacterial communities of H2 demonstrated significant differences from H1 and H3. Linear discriminant effect size analysis indicated that there were 11 and 14 different biomarkers in the H1 and H3 genotype, respectively, but 42 in the H2 genotype. Co-occurrence network analysis indicated that the rhizobacterial communities of H2 had a distinct network structure compared to those of the other two genotypes, whereas H1 and H3 had a similar pattern of co-occurrence network. Threshold indicator taxa analysis revealed that 63 genera responded significantly to NO3–-N content and 58 genera to NH4+-N/NO3–-N ratio. Moreover, the stochastic assembly process was found to be decreased with increasing NO3–-N content and fluctuated with increasing NH4+-N/NO3–-N ratio. All results indicated that the structure of poplar rhizobacterial communities were influenced by host genotypes, and available nitrogen might play a dominant role in the assembly of rhizobacterial communities. This study would promote the future selection and utilization of rhizobacteria in poplar breeding.

Abstract Chromatin interactions play important roles in regulating gene expression. However, the availability of genome-wide chromatin interaction data is limited. We develop a computational method, chromatin interaction neural network (ChINN), to predict chromatin interactions between open chromatin regions using only DNA sequences. ChINN predicts CTCF- and RNA polymerase II-associated and Hi-C chromatin interactions. ChINN shows good across-sample performances and captures various sequence features for chromatin interaction prediction. We apply ChINN to 6 chronic lymphocytic leukemia (CLL) patient samples and a published cohort of 84 CLL open chromatin samples. Our results demonstrate extensive heterogeneity in chromatin interactions among CLL patient samples.

Abstract Objective The aim of this study was to evaluate the predictive factors of central lymph node metastasis (CLNM) and BRAF V600E mutation in Chinese patients with papillary thyroid carcinoma (PTC). Methods A total of 943 PTC patients who underwent thyroidectomy from 2014 to 2016 at our hospital were enrolled. Those patients were divided into PTC > 10 mm and papillary thyroid microcarcinoma (PTMC) groups by tumor size. The BRAF V600E mutation was examined by quantitative real-time PCR. Univariate and multivariate analyses were used to examine risk factors associated with CLNM and the BRAF V600E mutation. Results The frequency of CLNM was 53% (505/943). Both univariate and multivariate analyses suggested that the risk factors for CLNM in PTC patients were male, younger age, and larger tumor size (P < 0.05). Coexistent Hashimoto thyroiditis (HT) was an independent protective factor against CLNM when the tumor was > 10 mm (P = 0.006). Stratified analysis revealed that male, age ≤ 30 years, and tumor size > 5 mm were independent risk factors for CLNM. The BRAF V600E mutation rate was 85%. Multivariate logistic regression analysis revealed that age (P < 0.001) and coexistent HT (P = 0.005) were independent predictive factors of BRAF V600E mutation in PTC patients. Only age was a risk factor for the BRAF V600E mutation when the tumor was > 10 mm (P = 0.004). In the PTMC group, the BRAF V600E mutation was significantly correlated with tumor size (P < 0.001) and coexistent HT (P = 0.03). Stratified analysis revealed that age > 30 years and tumor size > 5 mm were independent predictive factors of BRAF V600E mutation. Furthermore, the incidence of CLNM was significantly higher in BRAF V600E mutation-positive patients (P = 0.009) when the tumor was ≤ 5 mm. Conclusion The factors male, younger age (≤ 30 years), large tumor size (> 5 mm), and coexistent HT are independent predicative factors for CLNM. The BRAF V600E mutation is associated with both large size and without HT in PTMC patients, age > 30 years in the PTC > 10 mm group. The BRAF V600E mutation was an independent risk factor for CLNM when the tumor was ≤ 5 mm. For optimal management, these features should be comprehensively evaluated to determine the initial surgical approach for PTC patients.

Abstract Background The COVID-19 pandemic led to the implementation of various non-pharmaceutical interventions (NPI) as the Singapore government escalated containment efforts from DORSCON Orange to Circuit Breaker. NPI include mandatory mask wearing, hand hygiene, social distancing, and closure of schools and workplaces. Considering the similar mode of transmission of COVID-19 and other pathogens related to acute respiratory infections (ARI), the effects of NPI could possibly lead to decreased ARI attendances in the community. This study aims to determine the year-on-year and weekly changes of ARI attendances across a cluster of polyclinics following the implementation of NPI. Methods The effect of the nation-wide measures on the health-seeking behaviour of the study population was examined over three periods: (1) 9 weeks prior to the start of Circuit Breaker (DORSCON Orange period), (2) 8 weeks during the Circuit Breaker, and (3) 9 weeks after easing of Circuit Breaker. Data on ARI attendances for the corresponding periods in 2019 were also extracted for comparison and to assess the seasonal variations of ARI. The average weekly workday ARI attendances were compared with those of the preceding week using Wilcoxon signed rank test. Results ARI attendances dropped steadily throughout the study period and were 50–80% lower than in 2019 since Circuit Breaker. They remained low even after Circuit Breaker ended. Positivity rate for influenza-like illnesses samples in the community was 0.0% from the last week of Circuit Breaker to end of study period. Conclusions NPI and public education measures during DORSCON Orange and Circuit Breaker periods appear to be associated with the health-seeking behaviour of the public. Changing levels of perceived susceptibility, severity, benefits and barriers, and widespread visual cues based on the Health Belief Model may account for this change. Understanding the impact of NPI and shifts in the public’s health-seeking behaviour will be relevant and helpful in the planning of future pandemic responses.

Students with learning disabilities/difficulties in mathematics often apply ineffective procedures to solve word problems due to a lack of conceptual understanding of word problem solving, which results in poor mathematics performance and falling further behind the normal achievements of their peers. Current mathematics curriculum standards emphasize conceptual understanding in problem solving as well as higher-order thinking and reasoning, including all students. The purpose of this study was to evaluate the impact of a computer-assisted model-based problem-solving intervention program (MBPS) on elementary students’ word problem-solving performance by analyzing the error patterns. Results indicate that after the MBPS intervention, participants significantly improved their problem-solving performance and made fewer errors in solving problems across a range of additive word problem situations. Specifically, the participating students made their attempt to represent the mathematical relation, decontextualized from the word problem story, in the model equation before solving the problem, rather than blindly applying an operation or relying on the “keyword” strategy as they did during the preassessment. Implications of the study are discussed in the context of the National Council of Teachers of Mathematics’ calling for teaching big ideas to help students develop a deep understanding of mathematics knowledge.

Abstract Background The mechanism of body growth in mammals is poorly understood. Here, we investigated the regulatory networks involved in body growth through transcriptomic analysis of pituitary and epiphyseal tissues of smaller sized Debao ponies and Mongolian horses at the juvenile and adult stages. Results We found that growth hormone receptor (GHR) was expressed at low levels in long bones, although growth hormone (GH) was highly expressed in Debao ponies compared with Mongolian horses. Moreover, significant downregulated of the GHR pathway components m-RAS and ATF3 was found in juvenile ponies, which slowed the proliferation of bone osteocytes. However, WNT2 and PLCβ2 were obviously upregulated in juvenile Debao ponies, which led to premature mineralization of the bone extracellular matrix. Furthermore, we found that the WNT/Ca 2+ pathway may be responsible for regulating body growth. GHR was demonstrated by q-PCR and Western blot analyses to be expressed at low levels in long bones of Debao ponies. Treatment with WNT antagonistI decreased the expression of WNT pathway components (P

Mechanisms underlying gene repression and silencers remain poorly understood. Here the authors investigate the role of H3K27me3-rich regions in the genome, as defined from clusters of H3K27me3 peaks, in regulating gene expression via looping.

Objective To investigate the influencing factors of neoadjuvant chemotherapy (NAC) in estrogen receptor (ER) positive breast cancer and establish a prediction model of NAC efficacy. Methods A total of 321 ER positive breast cancer patients who received NAC treatment for 4 cycles followed by surgical treatment in our department from 2015 to 2018 were enrolled in this study. According to the efficacy evaluation criteria of solid tumors, the patients who achieved complete response (CR) or partial response (PR) after NAC were assigned into effective group, while those with stable disease (SD) and progressive disease (PD) into ineffective group. The differences of clinical and pathological parameters were retrospectively analyzed and compared between the 2 groups. Univariate and multivariate logistic regression analyses were applied to screen out the significant influencing factors. R Language was employed to establish the prediction models of NAC efficacy and pathological CR (pCR) rate of ER positive breast cancer patients. Then the prediction ability of the prediction models was evaluated by receiver operating characteristic (ROC) curve and correction curve. Results The overall effective rate of NAC and pCR were 75.39% and 15.26%, respectively, in the patients with ER positive breast cancer. Significant differences were seen in age, menstrual status, maximum tumor diameter, clinical node stage (cN), tumor blood supply, and ER and Ki-67 expression levels and chemotherapy regimen between the 2 groups (P < 0.05). Logistic analysis showed that cN, tumor blood supply, ER and Ki-67 expression levels were related to the efficacy of NAC (P < 0.05), while the rate of pCR after NAC was related to the maximal tumor diameter, tumor blood supply, and ER and Ki-67 expression levels (P < 0.05). The nomograms of predicting NAC efficacy and pCR in ER positive breast cancer patients were constructed with significant independent influencing factors. The area under ROC curve (AUC) of NAC Effectiveness Prediction Model for ER positive breast cancer patients was 0.785, and the cut-off value was (0.696, 0.760), and with calibration curve coinciding well with the reference standard. The AUC of pCR prediction model was 0.829 and the cut-off value was (0.673, 0.857), and the 2 curves were slightly biased. Conclusion Tumor blood supply, cN, ER and Ki-67 expression levels are the independent factors of NAC efficacy in ER positive breast cancer patients. The patients with axillary lymph node metastasis, low ER expression, high Ki-67 expression and good blood supply of tumor can achieve the best efficacy of NAC. Tumor maximal diameter, tumor blood supply, ER and Ki-67 expression levels are independent factors of pCR after NAC. The patients with small tumor, low expression of ER, high expression of Ki-67 and good blood supply of tumor have the highest probability of pCR after NAC. The established nomogram can primarily evaluate the benefit and probability of pCR in these patients.

Abstract Background Increasing evidence showed that carbamylated lipoprotein accelerated atherosclerosis. However, whether such modification of high-density lipoprotein (HDL) particles alters in type 2 diabetes mellitus (T2DM) patients and facilitates vascular complications remains unclear. We aimed to investigate the alteration of the carbamylation in HDL among T2DM patients and clarify its potential role in atherogenesis. Methods A total of 148 consecutive T2DM patients undergoning angiography and 40 age- and gender-matched control subjects were included. HDL was isolated from plasma samples, and the concentration of HDL carbamyl-lysine (HDL-CBL) was measured. Furthermore, the HDL from subjects and in-vitro carbamylated HDL (C-HDL) was incubated with endothelial cells and monocyte to endothelial cell adhesion. Adhesion molecule expression and signaling pathway were detected. Results Compared with the control group, the HDL-CBL level was remarkably increased in T2DM patients (6.13 ± 1.94 vs 12.00 ± 4.06 (ng/mg), P

Aims: To determine the association between urinary levels of perchlorate, nitrate and thiocyanate, and the prevalence of cardiovascular diseases (CVD) among general population. Methods: A total of 16, 570 participants were enrolled from the National Health and Nutrition Examination Surveys (NHANES). Urinary levels of perchlorate, nitrate and thiocyanate were measured using ion chromatography coupled with electrospray tandem mass spectrometry. Multivariable linear regressions and logistic regressions were performed to explore the associations of exposure to perchlorate, nitrate and thiocyanate, and the prevalence of total and specific CVD, including chronic heart failure (CHF), coronary heart disease (CHD), angina, heart failure and stroke. Restricted cubic splines were used to explore the nonlinearity. Results: Participants with CVD had a lower urinary level of nitrate and thiocyanate (all P

Abstract Background This study aimed to describe the design and present the baseline characteristics of a web-based lifestyle intervention program, which comprises of sequentially and simultaneously delivered intervention modules targeting physical activity (PA) and fruit and vegetable consumption (FVC) in Chinese college students. Methods The study adopted a randomized placebo-controlled trial, using the Health Action Process Approach (HAPA) and the Compensatory Carry-Over Action Model (CCAM) as the theoretical backdrops. 556 Chinese college students participated in the 8-week web-based lifestyle intervention program. All eligible participants were randomly assigned to one of four groups: 1) the PA-first arm which received a 4-week intervention addressing PA followed by a 4-week intervention addressing FVC; 2) the FVC-first arm which received a 4-week intervention addressing FVC followed by a 4-week intervention addressing PA; 3) the PA + FVC simultaneous arm that received an 8-week intervention addressing both PA and FVC at the same time; and 4) the placebo-control arm that received 8 weeks of general health information, which is not relevant for changing actual PA and FVC behaviors. Data collection includes four time-points: at the beginning and end of the intervention, and a 3-month and 12-month follow-up after the intervention. Results At baseline, 41.7% of participants were male and 58.3% were female. 41.0% of the participants did not meet the standard PA-recommendations, while 69.6% did not adhere to the standard FVC-recommendations. In total, only 19.6% of participants met both PA and FVC recommendations. Baseline characteristics across the four groups had no significant differences (all P = .17–.99), indicating successful randomization. Conclusions The preliminary results indicate a high prevalence of unhealthy lifestyles in college students in China, which further supports the need for web-based health intervention programs. This is also the first study that examines the comparative effectiveness of simultaneously and sequentially delivered lifestyle interventions in the Chinese population. These findings may contribute to the creation of future web-based health behavior change interventions. Trial registration ClinicalTrails.gov: NCT03627949, 14 August, 2018.

It has been reported that polysaccharides in wine can interact with tannins and other wine components and modify the sensory properties of the wine. Unfortunately, the contribution of polysaccharides to wine quality is poorly understood, mainly due to their complicated structure and varied composition. In addition, the composition and molecular structure of polysaccharides in different wines can vary greatly. In this study, the polysaccharides were isolated from pinot noir wine, then separated into high-molecular-weight (PNWP-H) and low-molecular-weight (PNWP-L) fractions using membrane-based ultrafiltration. Each polysaccharide fraction was further studied using size exclusion chromatography, UV–Vis, FT-IR, matrix-assisted laser desorption/ionization–high-resolution mass spectrometry, and gas chromatography-mass spectrometry (GC-MS). The results showed that PNWP-L and PNWP-H had different chemical properties and compositions. The FT-IR analysis showed that PNWPs were acidic polysaccharides with α- and β-type glycosidic linkages. PNWP-L and PNWP-H had different α- and β-type glycosidic linkage structures. FT-IR showed stronger antisymmetric and symmetric stretching vibrations of carboxylate anions of uronic acids in PNWP-L, suggesting more uronic acid in PNWP-L. The size exclusion chromatography results showed that over 72% of the PNWP-H fraction had molecular sizes from 25 kDa to 670 kDa. Only a small percentage of smaller molecular polysaccharides was found in the PNWP-H fraction. In comparison, all of the polysaccharides in the PNWP-L fraction were below 25 KDa, with a majority distributed approximately 6 kDa (95.1%). GC-MS sugar composition analysis showed that PNWP-L was mainly composed of galacturonic acid, rhamnose, galactose, and arabinose, while PNWP-H was mainly composed of mannose, arabinose, and galactose. The molecular size distribution and sugar composition analysis suggested that the PNWP-L primarily consisted of rhamnogalacturonans and polysaccharides rich in arabinose and galactose (PRAG). In comparison, PNWP-H were mostly mannoproteins and polysaccharides rich in arabinose and galactose (PRAG). Further research is needed to understand the impacts of these fractions on wine organoleptic properties.

This article analyzes the serum electrolyte disturbances of patients through deep learning algorithms. Among the 104 patients with electrolyte disturbances, 6 cases of serum potassium, sodium, chloride, calcium, phosphorus, and magnesium electrolyte disturbances have occurred, the proportion of occurrence The order is sodium > chlorine > calcium > potassium > phosphorus > magnesium. This paper proposes a deep learning algorithm for serum electrolyte disorder, and analyzes and implements the functions at various levels according to the characteristics of the Hadoop framework. The system includes electronic medical records shared storage, distributed realization of definite learning algorithms, classification and recognition of myocardial ischemia by deep learning, and Web system assisting doctor diagnosis, which lays the foundation for the construction of serum electrolyte disorder scientific research data center. In order to explore this relationship, without artificially extracting features, a deep learning model of convolution and long-term and short-term memory circulation neural network cascade was proposed to determine the positive or negative myocardial ischemia by classifying serum disorders. Conduct clinical experiments, including patients with suspected coronary heart disease and coronary angiography as the research object, taking coronary angiography results as the detection standard. Experimental results show that the model has an accuracy of 89.0% for detecting myocardial ischemia, a sensitivity of 91.7%, and a specificity of 81.5%. A linear combination model of CNN and LSTM is proposed to classify and recognize serum electrolyte disorders. Determine the learning theory to dynamically model the ST-T segment in the ECG to obtain serum electrolyte disturbance, which more vividly shows the changes in electrical information under myocardial ischemia. In order to reveal the relationship between serum electrolyte disturbance and myocardial ischemia, this paper builds a neural network model to learn and train serum electrolyte disturbance data to realize the classification of positive or negative myocardial ischemia. Tests on serum electrolyte disturbance data collected in clinical experiments show that this model can better achieve early detection of myocardial ischemia.

Abstract Background Urban parks play an important role in promoting physical activity (PA) among adults and especially among older city residents. According to the socioecological approach the association of physical environments and psychosocial factors in the context of park-based PA of elderly have not been systematically examined until now, let alone the relevance of the city (urban area) on a cross-cultural level. This study investigated selected aspects of (1) the association of psychosocial and park environmental factors with park-based physical activity (PBPA) of older people; and (2) the moderating effect of city on the association of these factors with PBPA. Methods A face-to-face survey was conducted of a mixed-culture sample from different urban surroundings in Hong Kong (HK) and Leipzig (L). In six parks of each city physically active elderly (> = 60 years; HK: n = 306; L: n = 311) were recruited. Multiple linear regressions were used to analyse the association between psychosocial factors and perceived environmental factors with PBPA and the moderating effect of city. Results Controlled for demographic variables, all other psychosocial factors were significantly related to PBPA, except social support. In terms of environmental factors, PBPA was positively associated with safety, attractiveness, features and negatively associated with park time distance. Controlled for demographic variables, psychosocial and environmental factors, the moderating effect of city on the associations of park features and park time distance with PBPA was not significant in HK. In contrast, there was a significant positive relationship for park features and a negative relationship for park time distance with PBPA in L. Conclusions Psychosocial and perceived environmental factors significantly influence PBPA of older people. City moderates the associations of these factors and independently contributes to park-based PA of the elderly. The different interactions of environmental factors and urban area for PBPA of elderly can support policy makers on the municipal level in choosing adequate strategies for promoting PA of older people in parks.

Microsporidia comprise a phylum of single cell, intracellular parasites and represent the earliest diverging branch in the fungal kingdom. The microsporidian parasite Nosema ceranae primarily infects honey bee gut epithelial cells, leading to impaired memory, suppressed host immune responses and colony collapse under certain circumstances. As the genome of N. ceranae is challenging to assembly due to very high genetic diversity and repetitive region, the genome was re-sequenced using long reads. We present a robust 8.8 Mbp genome assembly of 2,280 protein coding genes, including a high number of genes involved in transporting nutrients and energy, as well as drug resistance when compared with sister species Nosema apis. We also describe the loss of the critical protein Dicer in approximately half of the microsporidian species, giving new insights into the availability of RNA interference pathway in this group. Our results provided new insights into the pathogenesis of N. ceranae and a blueprint for treatment strategies that target this parasite without harming honey bees. The unique infectious apparatus polar filament and transportation pathway members can help to identify treatments to control this parasite.

Nosemosis C, a Nosema disease caused by microsporidia parasite Nosema ceranae, is a significant disease burden of the European honey bee Apis mellifera which is one of the most economically important insect pollinators. Nevertheless, there is no effective treatment currently available for Nosema disease and the disease mechanisms underlying the pathological effects of N. ceranae infection in honey bees are poorly understood. Iron is an essential nutrient for growth and survival of hosts and pathogens alike. The iron tug-of-war between host and pathogen is a central battlefield at the host-pathogen interface which determines the outcome of an infection, however, has not been explored in honey bees. To fill the gap, we conducted a study to investigate the impact of N. ceranae infection on iron homeostasis in honey bees. The expression of transferrin, an iron binding and transporting protein that is one of the key players of iron homeostasis, in response to N. ceranae infection was analysed. Furthermore, the functional roles of transferrin in iron homeostasis and honey bee host immunity were characterized using an RNA interference (RNAi)-based method. The results showed that N. ceranae infection causes iron deficiency and upregulation of the A. mellifera transferrin (AmTsf) mRNA in honey bees, implying that higher expression of AmTsf allows N. ceranae to scavenge more iron from the host for its proliferation and survival. The suppressed expression levels of AmTsf via RNAi could lead to reduced N. ceranae transcription activity, alleviated iron loss, enhanced immunity, and improved survival of the infected bees. The intriguing multifunctionality of transferrin illustrated in this study is a significant contribution to the existing body of literature concerning iron homeostasis in insects. The uncovered functional role of transferrin on iron homeostasis, pathogen growth and honey bee's ability to mount immune responses may hold the key for the development of novel strategies to treat or prevent diseases in honey bees.

Introduction Women of reproductive age (WRA) are a high-risk population for anaemia and micronutrient deficiencies. Evidence supports the role of periconceptional nutrition in the development of adverse pregnancy complications. However, in India, there are limited population-based data to guide evidence-based recommendations and priority setting. The objective of this study is to conduct a population-based biomarker survey of anaemia and vitamin B12 and folate status in WRA as part of a periconceptional surveillance programme in Southern India.Methods WRA (15–40 years) who are not pregnant or lactating and reside within 50 km2 of our community research site in Southern India will be screened and invited to participate in the biomarker survey at our research facility at Arogyavaram Medical Centre. After informed consent/assent, structured interviews will be conducted by trained nurse enumerators to collect sociodemographic, dietary, anthropometry, health and reproductive history data. Venous blood samples will be collected at enrolment; whole blood will be analysed for haemoglobin. Plasma, serum and red blood cells (RBCs) will be processed and stored

Abstract Ag/BiPbO2Cl nanosheet composites were successfully prepared by hydrothermal synthesis and photo-reduction. The morphology, microstructure, and optical properties of the as-prepared Ag/BiPbO2Cl nanosheet composites were characterized using TEM, XRD, and UV-Vis diffuse reflection spectroscopy. The prepared Ag/BiPbO2Cl nanosheet composites with 0.5 wt% Ag exhibit favorable photocatalytic activity, which is 3.6 times that of BiPbO2Cl nanosheet. The enhanced photocatalytic properties can be attributed to the inner electromagnetic field, higher visible light response range, excellent conductivity, and lower Fermi level of Ag.

Abstract Background Recent transitions in long-term care in the Netherlands have major consequences for community-dwelling older adults. A new paradigm expects them to manage and arrange their own care and support as much as possible. Technology can support this shift. A study has been conducted to explore the needs of community-dwelling frail older adults with regard to an online platform. An existing platform was subsequently modified, based upon these needs, resulting in an online community care platform (OCC-platform) comprising of care, health, and communication functions. The purpose of this platform was to support frail older adults in their independence and functioning, by stimulating self-care and providing reliable information, products and services. Methods The study used a User-Centred Design. The development processes involved the following steps: Step 1) Identification of the User Requirements. To assess the user requirements, direct observations (N = 3) and interviews (N = 14) were performed. Step 2) Modification of an Existing Online Platform. Based upon Step 1, available online platforms were explored to determine whether an existing useful product was available. Two companies collaborated in modifying such a platform; Step 3) Testing the Modified Platform. A total of 73 older adults were invited to test a prototype of the OCC-platform during 6 months, which comprised of two phases: (1) a training phase; and (2) a testing phase. Results An iterative process of modifications resulted in an interactive software concept on a Standard PC, containing 11 Functions. The Functions of ‘contacts’, ‘services’ and ‘messaging’, were by far, the most frequently used. The use was at its highest during the first 2 weeks of the testing and then its use steadily declined. The vast majority of the subjects (94%) were positive about the usability of the platform. Only a minority of the subjects (27%) indicated that the platform had added value for them. Conclusion The overall prospect was that an OCC-platform can contribute to the social participation and the self-management competencies of frail older adults, together with their social cohesion in the community. In order to validate these prospects, further research is needed on the characteristics and the impact of online platforms.

Clostridium difficile is a Gram-positive, spore-forming obligate anaerobe responsible for antibiotic-associated diarrhoea. Its virulence is associated with the production of endotoxins A and B and endospores, which can cause symptoms, such as diarrhoea, toxic megacolon, and pseudomembranous colitis. Given the increasing elderly population and the well-recognized problem of over-prescribing of broad-spectrum antibiotics, it is critical to have an understanding of molecular epidemiology and antimicrobial susceptibility in China. This study analyzed the toxin types and multilocus sequence typing (MLST) results of 74 clinical isolates of C. difficile after the glutamate dehydrogenase (GDH) screening test and anaerobic culture. The minimum inhibitory concentrations (MICs) of four different antibiotics were determined for all of the isolates, and the bacterial resistance mechanisms were investigated. Sixty-five strains (75%) were toxigenic, including 54 tcdA-positive, tcdB-positive, and cdtA/cdtB-negative strains (A+B+CDT−) and nine A−B+CDT− strains. Eleven strains (14.9%) were non-toxigenic. All clinical isolates were classified into 26 MLST genotypes, with the predominant type being ST-54 (18.9%). All isolates were susceptible to vancomycin. The tetracycline, clindamycin, and levofloxacin resistance rates were 1.4%, 36.5%, and 20.3%, respectively. The expression of tet(M), erm(B), and mutations of gyrA and/or gyrB were observed in the tetracycline-, clindamycin-, and levofloxacin-resistant isolates, respectively.

The expression of telomerase catalytic subunit hTERT is frequently upregulated in many cancers. Here, the authors show HoxC5 and miR-615-3p can negatively regulate hTERT to impede tumorigenesis by targeting the newly evolved cis-regulatory genomic elements of hTERT.

Natural products make up a large proportion of medicine available today. Cannabinoids from the plant Cannabis sativa is one unique class of meroterpenoids that have shown a wide range of bioactivities and recently seen significant developments in their status as therapeutic agents for various indications. Their complex chemical structures make it difficult to chemically synthesize them in efficient yields. Synthetic biology has presented a solution to this through metabolic engineering in heterologous hosts. Through genetic manipulation, rare phytocannabinoids that are produced in low yields in the plant can now be synthesized in larger quantities for therapeutic and commercial use. Additionally, an exciting avenue of exploring new chemical spaces is made available as novel derivatized compounds can be produced and investigated for their bioactivities. In this review, we summarized the biosynthetic pathways of phytocannabinoids and synthetic biology efforts in producing them in heterologous hosts. Detailed mechanistic insights are discussed in each part of the pathway in order to explore strategies for creating novel cannabinoids. Lastly, we discussed studies conducted on biological targets such as CB1, CB2 and orphan receptors along with their affinities to these cannabinoid ligands with a view to inform upstream diversification efforts.