bluuebunny/crossref_metadata_2025 huggingface dataset:
Population genomics and morphological features underlying the adaptive evolution of the eastern honey bee (Apis cerana)
Authors: Yancan Li , Tianle Chao , Yunhan Fan , Delong Lou , Guizhi Wang
Published: November 2019

Background

The adaptation of organisms to changing environments is self-evident, with the adaptive evolution of organisms to environmental changes being a fundamental problem in evolutionary biology. Bees can pollinate in various environments and climates and play important roles in maintaining the ecological balance of the earth.

Results

We performed an analysis of 462Apis cerana(A. cerana) specimens from 31 populations in 11 regions and obtained 39 representative morphological features. We selected 8A. ceranasamples from each population and performed 2b-RAD simplified genome sequencing. A total of 11,506 high-quality single nucleotide polymorphism (SNP) loci were obtained. For these SNPs, the minor allele frequency (MAF) was > 1%, the average number of unique labels for each sample was 49,055, and the average depth was 72.61x. The ratios of the unique labels of all samples were 64.27–86.33%.

Conclusions

Using 39 morphological characteristics as the data set, we proposed a method for the rapid classification ofA. cerana. Using genomics to assess population structure and genetic diversity, we found thatA. ceranahas a large genetic difference at the ecotype level. A comparison ofA. ceranain North China revealed that some physical obstacles, especially the overurbanization of the plains, have isolated the populations of this species. We identified several migration events in North China and Central China. By comparing the differences in the environmental changes in different regions, we found thatA. ceranahas strong potential for climate change and provides a theoretical basis for investigating and protectingA. cerana.
Foliar application of sodium selenate induces regulation in yield formation, grain quality characters and 2-acetyl-1-pyrroline biosynthesis in fragrant rice
Authors: Luo Haowen , Du Bin , He Longxin , Zheng Axiang , Pan Shenggang , Tang Xiangru
Published: November 2019

Background

Selenium (Se) is a beneficial element for higher plants and essential for mammals. To study the effect of the foliar application of sodium selenate on fragrant rice performance, a pot experiment was conducted in Guangdong, China. At the initial heading stage, one-time foliar application of sodium selenate with concentrations of 0, 10, 20, 30, 40 and 50 μmol·L− 1 (named CK, Se1, Se2, Se3, Se4 and Se5, respectively) were foliar applied on two fragrant rice varieties, ‘Meixiangzhan-2’ and ‘Xiangyaxiangzhan’.

Results

Selenate application at the initial heading stage not only improved the grain yield of fragrant rice by increasing the seed-setting rate and grain weight, but also promoted the grain quality by increasing crude protein contents and lowering the chalky rice rate. Furthermore, Se applications enhanced the biosynthesis of 2-acetyl-1- pyrroline (2-AP), the main aromatic compound, by increasing the contents of precursors (△1- pyrroline, proline and pyrroline-5-carboxylic acid (P5C)) and the activities of enzymes (proline dehydrogenase (PRODH), △1-pyrroline-5-carboxylic acid synthetase (P5CS), and ornithine aminotransferase (OAT)) in fragrant rice. The results also showed that foliar application of sodium selenate enhanced the antioxidant system of both varieties by promoting the activities of peroxidase (POD), superoxide dismutase (SOD), catalase (CAT) and reducing the contents of malondialdehyde (MDA). Furthermore, the real-time PCR analyses depicted that foliar application of selenate up-regulated the GPX1, GPX4 and CATC transcripts. The higher antioxidative enzymatic activities might strength the stress resistant to ensure the stability of yield in fragrant rice form abiotic stress.

Conclusions

Foliar applications of sodium selenate at the initial heading stage increased the grain 2-AP content by enhancing the biosynthesis-related enzymes and precursors. The grain yield and quality of fragrant rice also increased due to selenate application. Furthermore, foliar application of selenate promoted the activities of enzymes such as POD, SOD and CAT and up-regulated the expression of gene GPX4, GPX1 and CATC.
Modeling perinatal mortality in twins via generalized additive mixed models: a comparison of estimation approaches
Authors: Mullah Muhammad Abu Shadeque , Hanley James A. , Benedetti Andrea
Published: November 2019

Background

The analysis of twin data presents a unique challenge. Second-born twins on average weigh less than first-born twins and have an elevated risk of perinatal mortality. It is not clear whether the risk difference depends on birth order or their relative birth weight. This study evaluates the association between birth order and perinatal mortality by birth order-specific weight difference in twin pregnancies.

Methods

We adopt generalized additive mixed models (GAMMs) which are a flexible version of generalized linear mixed models (GLMMs), to model the association. Estimation of such models for correlated binary data is challenging. We compare both Bayesian and likelihood-based approaches for estimating GAMMs via simulation. We apply the methods to the US matched multiple birth data to evaluate the association between twins’ birth order and perinatal mortality.

Results

Perinatal mortality depends on both birth order and relative birthweight. Simulation results suggest that the Bayesian method with half-Cauchy priors for variance components performs well in estimating all components of the GAMM. The Bayesian results were sensitive to prior specifications.

Conclusion

We adopted a flexible statistical model, GAMM, to precisely estimate the perinatal mortality risk differences between first- and second-born twins whereby birthweight and gestational age are nonparametrically modelled to explicitly adjust for their effects. The risk of perinatal mortality in twins was found to depend on both birth order and relative birthweight. We demonstrated that the Bayesian method estimated the GAMM model components more reliably than the frequentist approaches.
Histological, immunohistochemical and mRNA gene expression responses in coeliac disease patients challenged with gluten using PAXgene fixed paraffin-embedded duodenal biopsies
Authors: Taavela Juha , Viiri Keijo , Popp Alina , Oittinen Mikko , Dotsenko Valeriia , Peräaho Markku , Staff Synnöve , Sarin Jani , Leon Francisco , Mäki Markku , Isola Jorma
Published: November 2019

Background

There is an unmet need for novel treatments, such as drugs or vaccines, adjunctive to or replacing a burdensome life-long gluten-free diet for coeliac disease. The gold standard for successful treatment is a healed small intestinal mucosa, and therefore, the outcome measures in proof-of-concept studies should be based on evaluation of small intestine biopsies. We here evaluated morphometric, immunohistochemical and messenger RNA (mRNA) expression changes in coeliac disease patients challenged with gluten using PAXgene fixed paraffin-embedded biopsies.

Methods

Fifteen coeliac disease patients were challenged with 4 g of gluten per day for 10 weeks and 24 non-coeliac patients served as disease controls. A wide array of histological and immunohistochemical staining and mRNA-based gene expression tests (RT-qPCR and RNAseq) were carried out.

Results

Digital quantitative villous height: crypt depth ratio (VH: CrD) measurements revealed significant duodenal mucosal deterioration in all coeliac disease patients on gluten challenge. In contrast, the Marsh-Oberhuber class worsened in only 80% of coeliac patients. Measuring the intraepithelial CD3+ T-lymphocyte and lamina propria CD138+ plasma cell densities simultaneously proved to be a meaningful new measure of inflammation. Stainings for γδ T cells and IgA deposits, where previously frozen samples have been needed, were successful in PAXgene fixed paraffin-embedded samples. Messenger RNA extraction from the same paraffin-embedded biopsy block was successful and allowed large-scale qRT-PCR and RNAseq analyses for gene expression. Molecular morphometry, using the mRNA expression ratio of villous epithelium-specific gene APOA4 to crypt proliferation gene Ki67, showed a similar significant distinction between paired baseline and post-gluten challenge biopsies as quantitative histomorphometry.

Conclusion

Rigorous digitally measured histologic and molecular markers suitable for gluten challenge studies can be obtained from a single paraffin-embedded biopsy specimen. Molecular morphometry seems to be a promising new tool that can be used in situations where assessing duodenal mucosal health is of paramount importance. In addition, the diagnostically valuable IgA deposits were now stained in paraffin-embedded specimens making them more accessible in routine clinics.
Item response analysis of the Geriatric Anxiety Inventory among the elderly in China: dimensionality and differential item functioning test
Authors: Li Zhongquan , Zhao Xia , Sheng Ang , Wang Li
Published: November 2019

Background

Anxiety symptoms are pervasive among elderly populations around the world. The Geriatric Anxiety Inventory (the GAI) has been developed and widely used in screening those suffering from severe symptoms. Although debates about its dimensionality have been mostly resolved by Molde et al. (2019) with bifactor modeling, evidence regarding its measurement invariance across sex and somatic diseases is still missing.

Methods

This study attempted to provide complemental evidence to the dimensionality debates of the GAI with Mokken scale analysis and to examine its measurement invariance across sex and somatic diseases by conducting differential item functioning (DIF) analysis among a sample of older Chinese adults. The data was from responses of a large representative sample (N = 1314) in the Chinese National Survey Data Archive, focusing on the mental health of elderly adults.

Results

The results of Mokken scale analysis confirmed the unidimensionality of the GAI, and DIF analysis indicated measurement invariance of this inventory across individuals with different sex and somatic diseases, with just a few items exhibiting item bias but all of them negligible.

Conclusions

All these findings supported the use of this inventory among Chinese elders to screen anxiety symptoms and to make comparisons across sex and somatic diseases.
PPAR-γ promotes p38 MAP kinase-mediated endothelial cell permeability through activating Sirt3
Authors: Zhao Zhenzhen , Zhang Xiaoxiu , Dai Yuanqiang , Pan Ke , Deng Yu , Meng Yan , Xu Tao
Published: November 2019

Background

Ischemia-reperfusion (I/R)-induced vascular dysfunction is the main factor to acute ischemic stroke. Sirt3 is one of the sirtuin family members, which plays an important role in the development of neurological diseases.

Methods

In this study, we constructed I/R injury model on HBMEC cells and induced the overexpression of Sirt3 in model cells. Meanwhile, the p38 activator U-46619 was used to examine the connection between Sirt3 and p38. We also examined the level of endothelial associated proteins, including occluding, ZO-1 and claudin-4 by using qRT-PCR and western blot.

Results

Our findings indicated that overexpression of Sirt3 decreased the permeability of model cells and promoted in the growth of endothelial cells. However, the activation of p38 could antagonize the function of Sirt3 in HBMEC cells. Moreover, Our results indicated a positive correlation between Sirt3 and inter-endothelial junction proteins. Importantly, PPAR-γ agonist and inhibitor were utilized to investigate the role of PPAR-γ in Sirt3 mediated cell function. Sirt3 was targeted by PPAR-γ in model cells.

Conclusions

Taken together, this research not only demonstrated PPAR-γ might benefit to the growth of endothelial cell though activating Sirt3 but also indicated its potential value in the treatment for ischemic stroke.
Expression of the luteinizing hormone receptor (LHR) in ovarian cancer
Authors: Xiong Shigang , Mhawech-Fauceglia Paulette , Tsao-Wei Denice , Roman Lynda , Gaur Rajesh K. , Epstein Alan L. , Pinski Jacek
Published: November 2019

We investigated the association of LHR expression in epithelial ovarian cancer (OC) with clinical and pathologic characteristics of patients. LHR expression was examined immunohistochemically using tissue microarrays (TMAs) of specimens from 232 OC patients. Each sample was scored quantitatively evaluating LHR staining intensity (LHR-I) and percentage of LHR (LHR-P) staining cells in tumor cells examined. LHR-I was assessed as no staining (negative), weak (+ 1), moderate (+ 2), and strong positive (+ 3). LHR-P was measured as 1 to 5, 6 to 50% and >  50% of the tumor cells examined. Positive LHR staining was found in 202 (87%) patients’ tumor specimens and 66% patients had strong intensity LHR expression. In 197 (85%) of patients, LHR-P was measured in > 50% of tumor cells. LHR-I was significantly associated with pathologic stage (p = 0.007). We found that 72% of stage III or IV patients expressed strong LHR-I in tumor cells. There were 87% of Silberberg’s grade 2 or 3 patients compared to 70% of grade 1 patients with LHR expression observed in > 50% of tumor cells, p = 0.037. Tumor stage was significantly associated with overall survival and recurrence free survival, p < 0.001 for both analyses, even after adjustment for age, tumor grade and whether patient had persistent disease after therapy or not. Our study demonstrates that LHR is highly expressed in the majority of OC patients. Both LHR-I and LHR-P are significantly associated with either the pathologic stage or tumor grade.
ACRNaCT trial protocol: efficacy of adjuvant chemotherapy in patients with clinical T3b/T4, N+ rectal Cancer undergoing Neoadjuvant Chemoradiotherapy: a pathology-oriented, prospective, multicenter, randomized, open-label, parallel group clinical trial
Authors:   ACRNaCT study group, Li Qingguo , Luo Dakui , Zhu Ji , Yang Lifeng , Liu Qi , Ma Yanlei , Liang Lei , Cai Sanjun , Zhang Zhen , Li Xinxiang
Published: November 2019

Background

The CAO/ARO/AIO-94 demonstrated that neoadjuvant chemoradiotherapy (CRT) could decrease the rate of local recurrence rather than distal metastases in advanced rectal cancer. Adjuvant chemotherapy (ACT) can eliminate micrometastasis, and render a better prognosis to rectal cancer. However, adoption of ACT mainly depends on the evidence from colon cancer. Neoadjuvant CRT can lead to tumor shrinkage in a number of patients with advanced rectal cancer. The administration of adjuvant therapy depending on pretreatment clinical stage or postoperative yield pathological (yp) stage remains controversial. At present, the clinical guidelines recommend ACT for patients with stage II/III (ypT3–4 N0 or ypTanyN1–2) rectal cancer following neoadjuvant CRT and surgery. However, the yp stage may influence the guidance of ACT.

Methods

According to the postoperative pathological stage, the present study was divided into two parts with different study design procedures. Patients will undergo different therapeutic strategies after collecting data related to postoperative pathological stage. For patients with pathologic complete response or yp stage I, the study was designed as a non-inferiority trial to compare the patients’ long-term outcomes in observational group and those in treatment group with 5-fluorouracil. For patients at yp stage II or III, the study was designed as a superiority trial to compare the oncological effect of oxaliplatin combined with 5-fluorouracil, in addition to 5-fluorouracil alone in ACT. The primary endpoint is 3-year disease-free survival (DFS). Secondary endpoints are 3-year, 5-year overall survival, 5-year DFS, and the rate of local recurrence and adverse events resulted from chemotherapy and the patients’ quality of life postoperatively.

Discussion

The ACRNaCT trial aims to investigate whether observation is not inferior than 5-fluorouracil for pathologic complete response or yp stage I, and indicate whether combined chemotherapy contains superior outcomes than 5-fluorouracil alone for yp stage II or III in patients receiving neoadjuvant CRT and surgery for locally advanced rectal cancer (LARC). This trial is expected to provide individualized adjuvant treatment strategies for LARC patients following neoadjuvant CRT and surgery.

Trial registration

The trial has been registered in ClinicalTrials.gov on January 30, 2018 (Registration No. NCT03415763), and also, that was registered in Chinese Clinical Trial Registry on November 12, 2018 (Registration No. ChiCTR1800019445).
Whole lesion histogram analysis of apparent diffusion coefficients on MRI predicts disease-free survival in locally advanced squamous cell cervical cancer after radical chemo-radiotherapy
Authors: Zhao Bo , Cao Kun , Li Xiao-Ting , Zhu Hai-Tao , Sun Ying-Shi
Published: November 2019

Background

The aim was to investigate the prognostic value of MR apparent diffusion coefficients (ADC) using histogram analysis (HA) in predicting disease-free survival (DFS) of cervical cancer after chemo-radiation therapy.

Methods

We retrospectively analyzed 103 women with pathologically proven squamous cell uterine cancer who received chemo-radiation therapy between 2009 and 2013. All patients were followed up for more than 2 years. Pre-treatment MR images were retrieved and imported for HA using an in-house developed software program based on 3D Slicer. Regions of interest of whole tumors were drawn manually on DWI with reference to T2WI. HA features (mean, max, min, 50, 10, 90%, kurtosis, and skewness) were extracted from apparent diffusion coefficient (ADC) maps and compared between the recurrence and non-recurrence groups after the 2-year follow-up. Univariate and multivariate Cox regression analysis was used to correlate ADC HA features and relevant clinical variables (age, grade, maximal diameter of tumor, FIGO stage, SCC-Ag) with DFS.

Results

One hundred three patients with stage IB-IV cervical cancers were followed up for 2.0–94.6 months (median 48.9 months). Twenty patients developed recurrence within 2 years. In the recurrence group, the min (P = 0.001) and 10% (P = 0.048) ADC values were significantly lower than those of the non-recurrence group. Univariate and multivariate Cox regression analysis revealed that ADCmin (P = 0.006, HR = 0.110) was significantly correlated with DFS.

Conclusion

Pre-treatment volumetric ADCmin in histogram analysis is an independent factor that is correlated with DFS in cervical cancer patients treated with chemo-radiation therapy.
Hospital discharges-based search of acute flaccid paralysis cases 2007–2016 in Italy and comparison with the National Surveillance System for monitoring the risk of polio reintroduction
Authors:   the Regional Reference Centres of the National Surveillance System for Acute flaccid paralysis, Stefanelli Paola , Bellino Stefania , Fiore Stefano , Fontana Stefano , Amato Concetta , Buttinelli Gabriele
Published: November 2019

Background

Acute flaccid paralysis (AFP) surveillance has been adopted globally as a key strategy for monitoring the progress of the polio eradication initiative. Hereby, to evaluate the completeness of the ascertainment of AFP cases in Italy, a hospital-discharges based search was carried out.

Methods

AFP cases occurring between 2007 and 2016 among children under 15 years of age were searched in the Italian Hospital Discharge Records (HDR) database using specific ICD-9-CM diagnostic codes. AFP cases identified between 2015 and 2016 were then compared with those notified to the National Surveillance System (NSS).

Results

Over a 10-year period, 4163 hospital discharges with diagnosis of AFP were reported in Italy. Among these, 956 (23.0%) were acute infective polyneuritis, 1803 (43.3%) myopathy, and 1408 (33.8%) encephalitis, myelitis and encephalomyelitis. During the study period, a decreasing trend was observed for all diagnoses and overall the annual incidence rate (IR) declined from 5.5 to 4.5 per 100,000 children. Comparing NSS with HDR data in 2015–2016, we found a remarkable underreporting, being AFP cases from NSS only 14% of those recorded in HDR. In particular, the acute infective polyneuritis cases reported to NSS accounted for 42.6% of those detected in HDR, while only 0.9% of myopathy cases and 13.1% of encephalitis/myelitis/encephalomyelitis cases have been notified to NSS. The highest AFP IRs per 100,000 children calculated on HDR data were identified in Liguria (17.4), Sicily (5.7), and Veneto (5.1) Regions; regarding the AFP notified to the NSS, 11 out of 21 Regions failed to reach the number of expected cases (based on 1/100,000 rate), and the highest discrepancies were observed in the Northern Regions. Overall, the national AFP rate was equal to 0.6, therefore did not reach the target value.

Conclusions

AFP surveillance data are the final measure of a country’s progress towards polio eradication. The historical data obtained by the HDR have been useful to assess the completeness of the notification data and to identify the Regions with a low AFP ascertainment rate in order to improve the national surveillance system.
Abdominal obesity increases metabolic risk factors in non-obese adults: a Hungarian cross-sectional study
Authors: Lukács Anita , Horváth Edina , Máté Zsuzsanna , Szabó Andrea , Virág Katalin , Papp Magor , Sándor János , Ádány Róza , Paulik Edit
Published: November 2019

Background

The prevalence of abdominal obesity is increasing worldwide. Adults with abdominal obesity have been reported to have increased risk of cardiometabolic disorders.

The aim of this study was to examine whether non-obese subjects (body mass index (BMI) < 25 kg/m2) with abdominal obesity examined in the framework of the Swiss–Hungarian Cooperation Programme had increased metabolic risk compared to participants without abdominal obesity.

Methods

A cross-sectional study was carried out in 5228 non-obese individuals. Data were collected between July 2012 and February 2016. Descriptive statistics, Pearson’s correlation analysis and multiple logistic regression models were applied, odds ratios (OR) with 95% confidence interval (CI) being the outcomes.

Results

607 (11.6%) out of the 5228 non-obese individuals had abdominal obesity. The correlation analysis indicated that the correlation coefficients between BMI and waist circumference (WC) were 0.610 in males and 0.526 in females. In this subgroup, the prevalence of high systolic blood pressure, high fasting blood glucose, and high total cholesterol and triglyceride levels were significantly higher. The logistic regression model based on these data showed significantly higher risk for developing high systolic blood pressure (OR = 1.53; 95% CI = 1.20–1.94), low HDL cholesterol (OR = 2.06; 95% CI = 1.09–3.89), and high trygliceride level (OR = 1.65; 95% CI = 1.27–2.16).

Conclusions

There was a very high, significant, positive correlation between WC and BMI. Abdominal obesity was found to be strongly related to certain metabolic risk factors among non-obese subjects. Hence, measuring waist circumference could be recommended as a simple and efficient tool for screening abdominal obesity and related metabolic risk even in non-obese individuals.
Exploring lay public and dental professional knowledge around HPV transmission via oral sex and oral cancer development
Authors: Brondani Mario A. , Siqueira Adriana B. , Alves Claudia Maria Coelho
Published: November 2019

Background

Human papillomavirus (HPV) has been associated with certain types of oropharyngeal cancers and yet, the level of knowledge that dental professionals and the lay public have in terms of HPV transmission, oral sexual activities, and oral cancer development needs exploration. The aim of this study was to assess the knowledge held by practicing dental professionals as well as the lay public regarding Human Papillomavirus (HPV) transmission through oral sex and subsequent oropharyngeal cancer development.

Methods

Textual data were collected from a public forum with dental professionals in.

Vancouver, who discussed the HPV-oral sex-oral cancer triad, and from survey data gathered from 212 lay public participants (also in Vancouver) who answered a 13-item questionnaire on the perceived risks of oral sex in terms of HPV infection and oropharyngeal cancer development. The data were analyzed statistically by age group, gender, and sexual orientation using descriptive statistics, while an ANOVA test was used to compare variation in the responses to the survey (p-value = 0.05).

Results

The forum engaged 46 health care professionals, many of whom were aware of the potential risks for head and neck cancer development due to HPV infection, while also questioning “how to effectively talk about HPV with patients.” The survey revealed that 34.5% of the participants believed that oral sex is an activity with no or low risk for the transmission of HPV, while 84% of participants believed the same sexual practices were of low or no-risk for HIV (Human Immunodeficiency Virus) transmission. Most participants (82%) never discussed oral sexual activities with their physicians or dentists/dental hygienists.

Conclusions

The general public remains mostly unaware of the potential links between HPV infection and oropharyngeal cancer. Physicians and dental providers should discuss oral sexual practice with their patients to raise awareness.
Pelvic floor muscle training in radical prostatectomy: a randomized controlled trial of the impacts on pelvic floor muscle function and urinary incontinence
Authors: Milios Joanne E. , Ackland Timothy R. , Green Daniel J.
Published: November 2019

Background

Pelvic floor muscle training (PFM) training for post-prostatectomy incontinence (PPI) is an important rehabilitative approach, but the evidence base is still evolving. We developed a novel PFM training program focussed on activating fast and slow twitch muscle fibres. We hypothesized that this training, which commenced pre-operatively, would improve PFM function and reduce PPI, when compared to a control group.

Methods

This randomized trial allocated 97 men (63 ± 7y, BMI = 25.4, Gleason 7) undergoing radical prostatectomy (RP) to either a control group (n = 47) performing low-volume rehabilitation, or an intervention group (n = 50). Both interventions commenced 5 weeks prior to surgery and continued for 12 weeks post-RP. Participants were assessed pre-operatively and at 2, 6 and 12 weeks post-RP using 24 h pad weights, International Prostate Symptom Score (IPSS), Expanded Prostate Cancer Index Composite for Clinical Practice (EPIC-CP) and real time ultrasound (RTUS) measurements of PFM function.

Results

Following RP, participants in the control group demonstrated a slower return to continence and experienced significantly more leakage (p < 0.05), measured by 24 h pad weight, compared to the intervention group, suggesting an impact of the prehabilitation protocol. PFM function measures were enhanced following RP in the intervention group. Secondary measures (IPSS, EPIC-CP and RTUS PFM function tests) demonstrated improvement across all time points, with the intervention group displaying consistently lower “bothersome” scores.

Conclusions

A pelvic floor muscle exercise program commenced prior to prostate surgery enhanced post-surgical measures of pelvic floor muscle function, reduced PPI and improved QoL outcomes related to incontinence.

Trial registration

The trial was registered in the Australia New Zealand Clinical Trials Registry and allocated asACTRN12617001400358. The trial was registered on 4/10/2017 and this was a retrospective registration.
Antiaging effect of a Jianpi-yangwei formula in Caenorhabditis elegans
Authors: Zeng Liling , Yang Zhimin , Yun Tianchan , Fan Shaoyi , Pei Zhong , Chen Ziwen , Sun Chen , Xu Fuping
Published: November 2019

Background

Jianpi-yangwei (JPYW), a traditional Chinese medicine (TCM), helps to nourish the stomach and spleen and is primarily used to treat functional declines related to aging. This study aimed to explore the antiaging effects and mechanism of JPYW by employing aCaenorhabditis elegansmodel.

Methods

Wild-typeC. elegansN2 worms were cultured in growth medium with or without JPYW, and lifespan analysis, oxidative and heat stress resistance assays, and other aging-related assays were performed. The effects of JPYW on the levels of superoxide dismutase (SOD) and the expression of specific genes were examined to explore the underlying mechanism of JPYW.

Results

Compared to control worms, JPYW-treated wild-type worms showed increased survival times under both normal and stress conditions (P < 0.05). JPYW-treated worms also exhibited enhanced reproduction, movement and growth and decreased intestinal lipofuscin accumulation compared to controls (P < 0.05). Furthermore, increased activity of SOD, downregulated expression levels of the proaging geneclk-2and upregulated expression levels of the antiaging genesdaf-16,skn-1, andsir-2.1were observed in the JPYW group compared to the control group.

Conclusion

Our findings suggest that JPYW extends the lifespan ofC. elegansand exerts antiaging effects by increasing the activity of an antioxidant enzyme (SOD) and by regulating the expression of aging-related genes. This study not only indicates that this Chinese compound exerts antiaging effects by activating and repressing target genes but also provides a proven methodology for studying the biological mechanisms of TCMs.
Interactive whiteboard use in clinical reasoning sessions to teach diagnostic test ordering and interpretation to undergraduate medical students
Authors: Gouzi Fares , Hédon Christophe , Blervaque Léo , Passerieux Emilie , Kuster Nils , Pujol Thierry , Mercier Jacques , Hayot Maurice
Published: November 2019

Background

Over-testing of patients is a significant problem in clinical medicine that can be tackled by education. Clinical reasoning learning (CRL) is a potentially relevant method for teaching test ordering and interpretation. The feasibility might be improved by using an interactive whiteboard (IWB) during the CRL sessions to enhance student perceptions and behaviours around diagnostic tests. Overall, IWB/CRL could improve their skills.

Methods

Third-year undergraduate medical students enrolled in a vertically integrated curriculum were randomized into two groups before clinical placement in either a respiratory disease or respiratory physiology unit: IWB-based CRL plus clinical mentoring (IWB/CRL + CM:n = 40) or clinical mentoring only (CM-only:n = 40). Feasibility and learning outcomes were assessed. In addition, feedback via questionnaire of the IWB students and their classmates (n = 233) was compared.

Results

Analyses of the IWB/CRL sessions (n = 40, 27 paperboards) revealed that they met validated learning objectives. Students perceived IWB as useful and easy to use. After the IWB/CRL + CM sessions, students mentioned more hypothesis-based indications in a test ordering file (p <  0.001) and looked for more nonclinical signs directly on raw data tests (p <  0.01) compared with students in the CM-only group. Last, among students who attended pre- and post-assessments (n = 23), the number of diagnostic tests ordered did not change in the IWB/CRL + CM group (+ 7%; p = N.S), whereas it increased among CM-only students (+ 30%;p <  0.001). Test interpretability increased significantly in the IWB/CRL + CM group (from 4.7 to 37.2%;p <  0.01) but not significantly in the CM-only group (from 2.4 to 9.8%;p = 0.36).

Conclusions

Integrating IWB into CRL sessions is feasible to teach test ordering and interpretation to undergraduate students. Moreover, student feedback and prospective assessment suggested a positive impact of IWB/CRL sessions on students’ learning.
Frequency of ubiquitous connectivity and associated factors among Mexican adolescents
Authors: Aguilar-Ye Arturo , Reyes-Morales Hortensia , Campero Lourdes , Garnelo-Bibiano Nicéforo
Published: November 2019

Background

There is limited information in Mexico - a middle-income country and a digital adopter with an important demographic bonus - regarding the potential use of technology and connectivity in health promotion among adolescent population.

Therefore, the objective of this study was to determine the proportion of adolescents connected ubiquitously; and to identify its associated factors for the further development of mobile health interventions.

Methods

An online survey of adolescents from state of Morelos, Mexico, was conducted in 2016. Explored individual socio-educational and school technological infrastructure characteristics and habits of use of mobile technologies. A logistic regression model was fitted to identify variables associated with ubiquitous connectivity.

Results

One thousand three hundred thirty-six students were included and six questionnaires (0.45%) were eliminated due to duplication of information. Fifty-four percent of participants were female, and the mean age was 16.31 ± 0.84 years. In total, 47% of students were ubiquitously connected. Associated factors to ubiquitous connectivity included better academic performance, the need to use Internet-based technologies, engaging in ludic activities on the Web and living in the state capital.

Conclusions

Ubiquitous connectivity it’s a desirable condition for strengthening health promotion programs focused on young population. Strategies including digital technology tools with potential to increase adolescent engagement should be explored and evaluated. However, it is necessary to recognize that there are additional factors that may influence the success of health promotion interventions.
Heart failure with insulin degludec versus glargine U100 in patients with type 2 diabetes at high risk of cardiovascular disease: DEVOTE 14
Authors: Pratley Richard E. , Husain Mansoor , Lingvay Ildiko , Pieber Thomas R. , Mark Thomas , Saevereid Hans A. , Møller Daniel Vega , Zinman Bernard ,   the DEVOTE Study Group
Published: November 2019

Background

Heart failure (HF) is a common cardiovascular complication of type 2 diabetes (T2D). This secondary analysis investigated baseline factors and treatment differences associated with risk of hospitalization for HF (hHF), and the possible association between severe hypoglycemia and hHF.

Methods

DEVOTE was a treat-to-target, double-blind cardiovascular outcomes trial in patients (n = 7637) with T2D and high cardiovascular risk randomized to insulin degludec (degludec) or insulin glargine 100 units/mL (glargine U100). The main endpoint of this secondary analysis was time to first hHF (standardized MedDRA Query definition). Severe hypoglycemia was adjudicated (American Diabetes Association definition). The main endpoint and the temporal association between severe hypoglycemia and hHF were analyzed with a Cox proportional hazards regression model. Predictors of time to first hHF were identified using baseline variables.

Results

Overall, 372 (4.9%) patients experienced hHF (550 events). There was no significant difference in the risk of hHF between treatments (hazard ratio [HR] 0.88 [0.72;1.08]95% CI, p = 0.227). Prior HF (HR 4.89 [3.90;6.14]95% CI, p ≤ 0.0001) was the strongest predictor of future hHF events. The risk of hHF significantly increased after (HR 2.2), and within a week after (HR 11.1), experiencing a severe hypoglycemic episode compared with before an episode.

Conclusions

In patients with T2D and high cardiovascular risk there were no treatment differences in terms of hHF. Prior HF was the strongest predictor of future hHF events, and there was an association between severe hypoglycemia and subsequent hHF. Further research should evaluate whether the risk of hHF can be modified by treatments aimed at reducing hypoglycemia.

Trial Registration NCT01959529
A panel of Transcription factors identified by data mining can predict the prognosis of head and neck squamous cell carcinoma
Authors: Zhang Boxin , Wang Haihui , Guo Ziyan , Zhang Xinhai
Published: November 2019

Background

Transcription factors (TFs) are responsible for the regulation of various activities related to cancer like cell proliferation, invasion, and migration. It is thought that, the measurement of TFs levels could assist in developing strategies for diagnosis and prognosis of cancer detection. However, due to lack of effective genome-wide tests, this cannot be carried out in clinical settings.

Methods

A complete assessment of RNA-seq data in samples of a head and neck squamous cell carcinoma (HNSCC) cohort in The Cancer Genome Atlas (TCGA) database was carried out. From the expression data of six TFs, a risk score model was developed and further validated in the GSE41613 and GSE65858 series. Potential functional roles were identified for the six TFs via gene set enrichment analysis.

Results

Based on our multi-TF signature, patients are stratified into high- and low-risk groups with significant variations in overall survival (OS) (median survival 2.416 vs. 5.934 years, log-rank test P < 0.001). The sensitivity and specificity evaluation of our multi-TF for 3-year OS in TCGA, GSE41613 and GSE65858 was 0.707, 0.679 and 0.605, respectively, demonstrating good reproducibility and robustness for predicting overall survival of HNSCC patients. Through multivariate Cox regression analyses (MCRA) and stratified analyses, we confirmed that the predictive capability of this risk score (RS) was not dependent on any of other factors like clinicopathological parameters.

Conclusions

With the help of a RS obtained from a panel of TFs expression signatures, effective OS prediction and stratification of HNSCC patients can be carried out.
Association between height and hypercholesterolemia in adults: a nationwide population-based study in Korea
Authors: Lee Mi Yeon , Nam Ga Eun , Han Kyungdo , Kim Da Hye , Kim Yang Hyun , Cho Kyung Hwan , Park Yong Gyu
Published: November 2019

Background

Previous studies reported that stature is inversely related to the risk of cardiovascular disease. However, there is limited evidence on the association between height and lipid profiles. We aimed to examine the association of height with total cholesterol and hypercholesterolemia based on the nationally representative dataset of Korean adults.

Methods

The data of 13,701 adults aged ≥19 years who participated in the Korea National Health and Nutrition Examination Survey (2013–2015) were used in this nationwide population-based cross-sectional study. Hypercholesterolemia was defined as a serum total cholesterol level ≥ 240 mg/dL or use of lipid-lowering medications. Multivariable linear regression and logistic regression analyses were used to examine the association of height with mean total cholesterol level and odds ratios (ORs) of hypercholesterolemia.

Results

Approximately 17% of participants had hypercholesterolemia. Mean total cholesterol levels decreased in the higher quartile (Q) groups of height after adjusting for confounding variables including age, sex, body mass index, smoking status, alcohol consumption, physical activity, income, educational level, hypertension, and diabetes mellitus (P for trend = 0.035). After adjusting for these potential confounding variables, the adjusted ORs of hypercholesterolemia were significantly lower in the Q3 and Q4 groups than in the Q1 group; ORs decreased in the higher quartile groups of height (OR: 0.83, 95% confidence interval: 0.71–0.99 in Q3; 0.81, 0.69–0.95 in Q4, P for trend = 0.007). The association between height (Q4 vs. Q1–Q3) and hypercholesterolemia was stronger in men or individuals without hypertension or diabetes than in women or individuals with such diseases.

Conclusions

Height is inversely associated with total cholesterol level and odds of hypercholesterolemia among Korean adults. Childhood environment related to short stature may be associated with hypercholesterolemia and cardiovascular health in adulthood.
Beyond the target area: an integrative view of tDCS-induced motor cortex modulation in patients and athletes
Authors: Morya Edgard , Monte-Silva Kátia , Bikson Marom , Esmaeilpour Zeinab , Biazoli Claudinei Eduardo , Fonseca Andre , Bocci Tommaso , Farzan Faranak , Chatterjee Raaj , Hausdorff Jeffrey M. , da Silva Machado Daniel Gomes , Brunoni André Russowsky , Mezger Eva , Moscaleski Luciane Aparecida , Pegado Rodrigo , Sato João Ricardo , Caetano Marcelo Salvador , Sá Kátia Nunes , Tanaka Clarice , Li Li Min , Baptista Abrahão Fontes , Okano Alexandre Hideki
Published: November 2019

Transcranial Direct Current Stimulation (tDCS) is a non-invasive technique used to modulate neural tissue. Neuromodulation apparently improves cognitive functions in several neurologic diseases treatment and sports performance. In this study, we present a comprehensive, integrative review of tDCS for motor rehabilitation and motor learning in healthy individuals, athletes and multiple neurologic and neuropsychiatric conditions. We also report on neuromodulation mechanisms, main applications, current knowledge including areas such as language, embodied cognition, functional and social aspects, and future directions. We present the use and perspectives of new developments in tDCS technology, namely high-definition tDCS (HD-tDCS) which promises to overcome one of the main tDCS limitation (i.e., low focality) and its application for neurological disease, pain relief, and motor learning/rehabilitation. Finally, we provided information regarding the Transcutaneous Spinal Direct Current Stimulation (tsDCS) in clinical applications, Cerebellar tDCS (ctDCS) and its influence on motor learning, and TMS combined with electroencephalography (EEG) as a tool to evaluate tDCS effects on brain function.
Identification of key biomarkers associated with development and prognosis in patients with ovarian carcinoma: evidence from bioinformatic analysis
Authors: Shen Jiayu , Yu Shuqian , Sun Xiwen , Yin Meichen , Fei Jing , Zhou Jianwei
Published: November 2019

Background

Ovarian cancer (OC) is the deadliest cause in the gynecological malignancies. Most OC patients are diagnosed in advanced stages with less than 40% of women cured. However, the possible mechanism underlying tumorigenesis and candidate biomarkers remain to be further elucidated.

Results

Gene expression profiles of GSE18520, GSE54388, and GSE27651 were available from Gene Expression Omnibus (GEO) database with a total of 91 OC samples and 22 normal ovarian (OV) tissues. Three hundred forty-nine differentially expressed genes (DEGs) were screened between OC tissues and OV tissues via GEO2R and online Venn software, followed by KEGG pathway and gene ontology (GO) enrichment analysis. The enriched functions and pathways of these DEGs contain male gonad development, cellular response to transforming growth factor beta stimulus, positive regulation of transcription from RNA polymerase II promoter, calcium independent cell-cell adhesion via plasma membrane cell adhesion molecules, extracellular matrix organization, pathways in cancer, cell cycle, cell adhesion molecules, PI3K-AKT signaling pathway, and progesterone mediated oocyte maturation. The protein-protein network (PPI) was established and module analysis was carried out using STRING and Cytoscape. Next, with PPI network analyzed by four topological methods in Cytohubba plugin of Cytoscape, 6 overlapping genes (DTL, DLGAP5, KIF15, NUSAP1, RRM2, andTOP2A) were eventually selected. GEPIA and Oncomine were implemented for validating the gene expression and all the six hub genes were highly expressed in OC specimens compared to normal OV tissues. Furthermore, 5 of 6 genes except forDTLwere associated with worse prognosis using Kaplan Meier-plotter online tool and 3 of 6 genes were significantly related to clinical stages, includingRRM2, DTL, andKIF15. Additionally, cBioPortal showed thatTOP2AandRRM2were the targets of cancer drugs in patients with OC, indicating the other four genes may also be potential drug targets.

Conclusion

Six hub genes (DTL, DLGAP5, KIF15, NUSAP1, RRM2, andTOP2A) present promising predictive value for the development and prognosis of OC and may be used as candidate targets for diagnosis and treatment of OC.
Predictors of good response to conventional synthetic DMARDs in early seronegative rheumatoid arthritis: data from the ESPOIR cohort
Authors: Lukas Cédric , Mary Julia , Debandt Michel , Daïen Claire , Morel Jacques , Cantagrel Alain , Fautrel Bruno , Combe Bernard
Published: November 2019

Background and objective

Early seronegative rheumatoid arthritis (RA) is considered a specific entity, especially regarding diagnostic issues and prognosis. Little is known about its potentially different initial clinical presentation and outcome. We aimed to determine predictors of good response to conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) in seronegative RA patients with early inflammatory arthritis.

Patients and methods

Patients from the ESPOIR cohort with early inflammatory arthritis fulfilling the 2010 ACR/EULAR classification criteria for RA despite negativity for both rheumatoid factor and anti-CCP antibodies. The primary endpoint was a good or moderate EULAR response assessed after 1 year of follow-up, given at least 3 months of treatment with a csDMARD. Secondary objectives were to compare the early therapeutic response to methotrexate (MTX) and leflunomide (LEF) versus other csDMARDs (hydroxychloroquine, sulfasalazine) and to identify factors associated with functional disability (Health Assessment Questionnaire-Disability Index [HAQ-DI] > 0.5 at 1 year) and structural progression (van der Heijde-modified total Sharp score > 1 and > 5 points at 1 year). Logistic regression analysis was used to determine independent predictors of outcomes.

Results

One hundred seventy-two patients were analyzed. Overall, 98/172 (57%) patients received MTX during the first year of follow-up. A good or moderate EULAR response at 1 year was associated with early use of csDMARDs (i.e., within 3 months after the first joint swelling) on univariate and multivariable analysis (odds ratio = 2.41 [95% confidence interval 1.07–5.42], p = 0.03). Response rates were not affected by other classical prognostic factors (i.e., baseline DAS28). Presence of erosions at baseline was associated with Sharp score progression > 1 point and > 5 points (both p = 0.03) at 1 year. HAQ-DI ≥ 1 at inclusion and active smoking were significantly associated with HAQ-DI > 0.5 at 1 year.

Conclusion

Our results suggest that delay in initiation of csDMARD more than baseline clinical, biological, or imaging features predominantly affects the outcome in early seronegative RA. These findings confirm that the usual therapeutic concepts in RA (early treatment, tight control, and treat-to-target) should be applied similarly to both seropositive and seronegative disease forms.

Trial registration

ClinicalTrials.gov: NCT03666091. Registered September 11, 2018.