bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract
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

Abstract
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

Abstract
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

AbstractWe 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

Abstract
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

Abstract
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

Abstract
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

AbstractBackgroundThe 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.MethodsA 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.Results607 (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).ConclusionsThere 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

Abstract
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

AbstractBackgroundPelvic 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.MethodsThis 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.ResultsFollowing 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.ConclusionsA 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 registrationThe 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

AbstractBackgroundJianpi-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.MethodsWild-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.ResultsCompared 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.ConclusionOur 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.