bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genetic Variations at rs3129891 and rs77005575 are Associated With Reduced Expression of Enteric α-defensins in IBD Patients
Authors: Deng Qiliang , Tan Gao , Deng Feihong , Zhi Fachao 
Published: August 2019

Background and Aims:
Human enteric antimicrobial peptides composed predominantly of human enteric α-defensins (HD5 and HD6) are important in the mucosal antimicrobial barrier. Previous studies have identified that genetic variations at rs2066844, rs2066845, rs2066847 are associated with diminished enteric α-defensins in ileal Crohn’s disease (CD). However, genetic variations associated with enteric antimicrobial peptides in colonic inflammatory bowel disease (IBD) remain unclear. To investigate it, we compared the colonic expression of antimicrobial peptides with respect to genotypes at 22 IBD-associated single-nucleotide polymorphisms (SNPs).

Materials and Methods:
In total, 16 controls and 102 colonic IBD patients including 42 ulcerative colitis (UC) and 60 CD were studies. Mutation assay was performed to determine their genotypes at 22 IBD-associated SNPs. Real-time PCR was performed to determine the colonic mRNA expression of HD5, HD6, lysozyme, and secretory phospholipase A2.

Results:
Mutant genotypes at rs2066844, rs2066845, rs2066847 were not found, and only SNPs rs3129891 and rs77005575 were associated with enteric α-defensin expression in colonic IBD. In both inflamed and noninflamed tissues, colonic expression of HD5 and HD6 was significantly decreased in UC and CD patients carrying rs3129891 homozygous mutant genotype. And their colonic expression was significantly decreased in inflamed but not noninflamed tissues from UC patients carrying rs77005575 homozygous mutant genotype. However, both lysozyme and secretory phospholipase A2 in UC and CD were unaffected by rs3129891 and rs77005575 genotypes.

Conclusions:
As enteric α-defensins play critical roles in the mucosal antimicrobial barrier, their reduced expression may partly explain the microbial-induced mucosal inflammation in colonic IBD patients, especially in patients carrying rs3129891 and rs77005575 mutant genotypes.
Chronic Disease Medication Adherence After Initiation of Buprenorphine for Opioid Use Disorder
Authors: Chang Hsien-Yen , Daubresse Matthew , Saloner Brendan , Alexander G. Caleb 
Published: August 2019

Background:
Although buprenorphine is an evidence-based treatment for opioid use disorder (OUD), it is unknown whether buprenorphine use may affect patients’ adherence to treatments for chronic, unrelated conditions.

Objectives:
To quantify the effect of buprenorphine treatment on patient adherence to 5 therapeutic classes: (1) antilipids; (2) antipsychotics; (3) antiepileptics; (4) antidiabetics; and (5) antidepressants.

Research Design:
This was a retrospective cohort study.

Subjects:
We started with 12,719 commercially ensured individuals with a diagnosis of OUD and the buprenorphine initiation between January 2011 and June 2015 using Truven Health’s MarketScan data. Individuals using any of the 5 therapeutic classes of interest were included.

Measures:
Within the 180-day period post buprenorphine initiation, we derived 2 daily indicators: having buprenorphine and having chronic medication on hand for each therapeutic class of interest. We applied logistic regression to assess the association between these 2 daily indicators, adjusting for demographics, morbidity, and baseline adherence.

Results:
Across the 5 therapeutic classes, the probability with a given treatment on hand was always higher on days when buprenorphine was on hand. After adjustment for demographics, morbidity, and baseline adherence, buprenorphine was associated with a greater odds of adherence to antilipids [odds ratio (OR), 1.27; 95% confidence interval (CI), 1.04–1.54], antiepileptics (OR, 1.22; CI, 1.10–1.36) and antidepressants (OR, 1.42; CI, 1.32–1.60).

Conclusions:
Using buprenorphine to treat OUD may increase adherence to treatments for chronic unrelated conditions, a finding of particular importance given high rates of mental illness and other comorbidities among many individuals with OUD.
Defining Pancreatitis as a Risk Factor for Pancreatic Cancer
Authors: Syed Aslam , Babich Olivia , Thakkar Payal , Patel Arjun , Abdul-Baki Heitham , Farah Katie , Morrissey Suzanne , Mitre Marcia , Dhawan Manish , Kochhar Gursimran , Kulkarni Abhijit , Thakkar Shyam 
Published: August 2019

Objectives
Acute and/or chronic pancreatitis has been implicated as an important risk factor for pancreatic cancer; however, the incidence and temporal relationship of pancreatitis before pancreatic cancer diagnosis are unclear. We aim to understand the role and incidence of pancreatitis temporally with the development of pancreatic cancer.

Methods
A population-based study was used to investigate a temporal relationship between pancreatitis and pancreatic cancer diagnoses. Intervals of 3, 6, 12, 24, and 36 months were developed. Demographical data including age, sex, and race were also recorded and analyzed.

Results
A total of 50,080 patients were found to have a diagnosis of pancreatic cancer, of which 7420 (14.8%) had prior diagnoses of pancreatitis. Of those, 92% were between the ages of 40 and 89 years. African Americans had a higher rate of pancreatitis before cancer diagnosis when compared with whites (21.2% vs 14.8%, P < 0.0001). Further analysis revealed that pancreatitis occurred in 81.3% of patients 3 months before a diagnosis of pancreas cancer and 98.9% had established diagnoses of pancreatic cancer within 3 years.

Conclusions
Screening of patients older than 40 years who have pancreatitis and unclear etiology of pancreatitis may be warranted, especially in African Americans and male individuals.
Expression of Monocarboxylate Transporter 1 Is Associated With Better Prognosis and Reduced Nodal Metastasis in Pancreatic Ductal Adenocarcinoma
Authors: Sukeda Aoi , Nakamura Yuka , Nishida Yasunori , Kojima Motohiro , Gotohda Naoto , Akimoto Tetsuo , Ochiai Atsushi 
Published: August 2019

Objectives
Because lactate is believed to support tumor growth, monocarboxylate transporters (MCTs), which transport lactate, have been investigated in multiple tumors. However, the significance of MCTs in pancreatic cancer is unclear.

Methods
A retrospective survey was conducted on 240 patients who underwent surgical resection for pancreatic ductal adenocarcinoma without preoperative treatment. The expression of MCT1, MCT2, MCT3, MCT4, and the glucose transporter 1 (GLUT1) was assessed in tumor cells and cancer-associated fibroblasts (CAFs) by tissue microarrays and immunohistochemistry. The impact of their expression on patient outcome and clinicopathological characteristics was also analyzed.

Results
In tumor cells, MCT1, MCT2, MCT3, MCT4, and GLUT1 were detected in 52 (22%), 31 (13%), 149 (62%), 204 (85%), and 235 (98%) cases, respectively. In CAFs, MCT2, MCT4, and GLUT1 were detected in 9 (3.8%), 178 (74%), and 36 (15%) cases, respectively. In tumor cells, MCT1 expression was associated with extended overall and progression-free survival and decreased nodal metastasis. Conversely, MCT4 expression in CAFs was associated with shortened survival.

Conclusions
In tumor cells, MCT1 expression is associated with better prognosis and reduced nodal metastasis in pancreatic cancer, contrary to findings of past in vitro studies. Conversely, MCT4 expression in CAFs is indicative of worse prognosis.
Mutational Patterns in Pancreatic Juice of Intraductal Papillary Mucinous Neoplasms and Concomitant Pancreatic Cancer
Authors: Takano Shinichi , Fukasawa Mitsuharu , Kadokura Makoto , Shindo Hiroko , Takahashi Ei , Hirose Sumio , Fukasawa Yoshimitsu , Kawakami Satoshi , Hayakawa Hiroshi , Maekawa Shinya , Mochizuki Kunio , Kawaida Hiromichi , Kono Hiroshi , Itakura Jun , Sato Tadashi , Ichikawa Daisuke , Enomoto Nobuyuki 
Published: August 2019

Objectives
The aims of this study were to identify genetic characteristics of intraductal papillary mucinous neoplasm (IPMN)-associated pancreatic ductal carcinoma (PDC) and to detect these markers using pancreatic juice.

Methods
From 76 cases, 102 tissues were obtained: 29 cases were noninvasive IPMN, 18 were PDC derived from IPMN (D-PDC; noninvasive part, n = 16; invasive part, n = 18), and 29 were PDC concomitant with IPMN (C-PDC; IPMN part, n = 10; PDC part, n = 29). Moreover, pancreatic juice samples from 28 cases were obtained (noninvasive IPMN, n = 13; D-PDC, n = 7; C-PDC, n = 8). Fifty-one cancer-related genes were analyzed by next-generation sequencing.

Results

TP53 mutation rates in D-PDC, C-PDC, and noninvasive IPMN were 67%, 66%, and 10%, respectively. Moreover, KRAS mutational patterns between 2 simultaneous tumors differed in 1 (6.3%) of the 16 D-PDC cases and in 8 (80%) of the 10 C-PDC cases (P = 0.0006). TP53 or multiple KRAS mutations were detected using pancreatic juice more frequently in C-PDC cases than in noninvasive IPMN cases (75% and 23%, respectively, P = 0.03).

Conclusions
Multiple KRAS mutations along with TP53 mutation are genetic markers for C-PDC, which could be detected using pancreatic juice preoperatively.
18F-Fluorodeoxyglucose Positron Emission Tomography Predicts Treatment Efficacy and Clinical Outcome for Patients With Pancreatic Carcinoma
Authors: Wang Li , Dong Ping , Shen Guohua , Hou Shengzhong , Zhang Yi , Liu Xubao , Tian Bole 
Published: August 2019

Objectives

18F-Fluorodeoxyglucose positron emission tomography (FDG-PET) has been an important modality for detecting malignancies. Recently, an increasing number of studies reported the utility of FDG-PET parameters in predicting clinical outcomes and treatment assessment in variety of cancers. We aimed at clarifying both the prognostic role and assessment value of FDG-PET in pancreatic carcinoma.

Methods
We systematically searched electronic databases of PubMed, Embase, Cochrane Library, and Web of Science to identify relevant studies to conduct this meta-analysis. Comparative analyses of the pooled hazard ratio (HR) for overall survival were performed to assess the utility of FDG-PET parameters in prognosis evaluation and treatment assessment by random-effect model.

Results
Twenty-three studies with 1762 patients met the inclusion criteria of this meta-analysis. The pooled results revealed that greater maximum standardized uptake value of the primary tumor was significantly correlated with poorer overall survival (HR, 1.31; 95% confidence interval, 1.15–1.50; P < 0.001). Besides, greater reduction of maximum standardized uptake value after treatments indicated significant better overall survival (HR, 0.68; 95% confidence interval, 0.47–0.98; P = 0.037).

Conclusions

18F-Fluorodeoxyglucose positron emission tomography parameters might be helpful not only for predicting survival outcome but also for selecting potentially efficacious treatments in patients with pancreatic carcinoma.
Pancreatic Fluid Interleukin-1β Complements Prostaglandin E2 and Serum Carbohydrate Antigen 19-9 in Prediction of Intraductal Papillary Mucinous Neoplasm Dysplasia
Authors: Simpson Rachel E. , Yip-Schneider Michele T. , Flick Katelyn F. , Wu Huangbing , Colgate Cameron L. , Schmidt C. Max 
Published: August 2019

Objectives
We sought to determine if interleukin (IL)-1β and prostaglandin E2 (PGE2) (inflammatory mediators in pancreatic fluid) together with serum carbohydrate antigen (CA) 19-9 could better predict intraductal papillary mucinous neoplasm (IPMN) dysplasia than individual biomarkers alone.

Methods
Pancreatic cyst fluid (n = 92) collected via endoscopy or surgery (2003–2016) was analyzed for PGE2 and IL-1β (enzyme-linked immunosorbent assay). Patients had surgical pathology-proven IPMN. Threshold values (PGE2 [>1100 pg/mL], IL-1β [>20 pg/mL], and serum CA 19-9 [>36 U/mL]) were determined.

Results
Levels of IL-1β were higher in high-grade dysplasia (HGD)/invasive-IPMN (n = 42) compared with low/moderate IPMN (n = 37) (median [range], 54.6 [0–2671] vs 5.9 [0–797] pg/mL; P < 0.001; area under curve [AUC], 0.766). Similarly, PGE2 was higher in HGD/invasive IPMN (n = 45) compared with low/moderate IPMN (n = 47) (median [range], 1790 [20–15,180] vs. 140 [10–14,630] pg/mL; P < 0.001; AUC, 0.748). Presence of elevated PGE2 and IL-1β (AUC, 0.789) provided 89% specificity and 82% positive predictive value (PPV) for HGD/invasive IPMN. Elevated levels of all 3 provided 100% specificity and PPV for HGD/invasive IPMN.

Conclusions
Cyst fluid PGE2, IL-1β, and serum CA 19-9 in combination optimize specificity and PPV for HGD/invasive IPMN and may help build a panel of markers to predict IPMN dysplasia.
Pancreatic Function in Chronic Pancreatitis
Authors: Brownell Jefferson N. , Schall Joan I. , Stallings Virginia A. 
Published: August 2019

Objectives
Reliable pancreatic function tests in patients with chronic pancreatitis (CP) are needed. This cohort study identified malabsorption in people with CP compared with healthy people and then investigated short-term pancreatic enzyme replacement therapy (PERT) and fat malabsorption, nutritional status, and quality of life (QOL).

Methods
Subjects with CP were evaluated before and after PERT and compared with the healthy cohort using coefficient of fat absorption (CFA), stool bomb calorimetry, and the malabsorption blood test (MBT). Anthropometrics, micronutrients, and QOL data were collected. Group means at baseline and after PERT were analyzed.

Results
The 24 subjects with CP had greater stool energy loss (5668 cal/g [standard deviation {SD}, 753] vs 5152 cal/g [SD, 418], P < 0.01), reduced triglyceride absorption (MBT, 8.3 mg·h/dL [SD, 4.3] vs 17.7 mg·h/dL [SD, 10.3], P < 0.001), lower fat intake, and poorer QOL. Differences in CFA were not significant (90.9% [SD, 12.8] vs 95.4% [SD, 9.3]). After PERT, triglyceride absorption (Δ = 1.7 [SD, 3], P < 0.05) and QOL increased.

Conclusions
The MBT detected changes in triglyceride absorption in the absence of CFA changes. The MBT may be helpful in guiding PERT initiation in patients with CP before significant morbidity.
Detection of Reg3γ by Immunohistochemistry in Cerulein-Induced Model of Acute Pancreatic Injury in Mice and Rats
Authors: Shea Katherine , Rouse Rodney 
Published: August 2019

Objective
In a continuation of previous work, Reg3γ protein was further evaluated as a biomarker of pancreatic injury using immunohistochemistry in an additional species.

Methods
Mice and rats were treated with intraperitoneal cerulein injections, creating acute pancreatic injury. Mice received 2, 4, or 6 doses, and rats received 1, 2, or 3 doses of cerulein creating low, medium, and high treatment groups. Control animals were dosed with phosphate-buffered saline at corresponding volumes and intervals. Groups of 6 animals were killed 1, 3, 6, 24, and 48 hours after final treatments. Reg3γ immunohistochemical staining and image analysis were performed on pancreatic tissue obtained 6, 24, or 48 hours after control or cerulein treatment. Staining was quantified using image analysis software to calculate area of positivity as a percentage of total tissue area.

Results
Percent positivity of Reg3γ in both species rose by 6 hours, peaked by 24 hours across all 3 cerulein doses, and dropped significantly by 48 hours. In high-dose rats with accompanying gene expression data, Reg3γ gene expression corresponded temporally with quantitative staining data.

Conclusions
Reg3γ staining quantified through image analysis showed a time- and dose-response in cerulein-treated mice and rats.
Inflammation Promotes Progression of Pancreatic Cancer Through WNT/β-Catenin Pathway-Dependent Manner
Authors: Ren Rui , Yu Jie , Zhang Yan , Wang Sheng-Fei , Guo Xia , Shen Meng , Xu Meng-Dan , Jiang Min , Zhi Qiaoming , Chen Kai , Tao Min , Wu Meng-Yao , Gu Dong-Mei , Li Wei 
Published: August 2019

Objective
Identify the molecular mechanism of inflammatory stimuli induced pancreatic cancer progression.

Methods
RNA-seq, microarray assay and bioinformatics analyses were used to identify differentially expressed genes. Immunohistochemical staining was performed to evaluate CD68, CD163, β-catenin, CD103, CCL3 markers. Quantitative real-time polymerase chain reaction (qRT-PCR), luciferase reporter assay, apoptosis assay, wound healing assay and immunofluorescence were performed to study the relationship of inflammatory stimuli and WNT/β-catenin pathway.

Results
Differentially expressed genes of macrophage-conditioned medium-treated pancreatic cancer cells were related with WNT/β-catenin pathway. Inflammatory stimuli could activate WNT/β-catenin signaling pathway. In 106 pancreatic cancer patients, nuclear β-catenin expression of CD68-high group was much higher than CD68-low group (P < 0.05), as same as CD163 (P < 0.05). Inflammatory stimuli downregulated the expression of CCL3 via WNT/β-catenin pathway and inhibited the chemotaxis of CD103+ dendritic cells. Six pancreatic cancer prognosis associating genes were upregulated by inflammatory stimuli via WNT/β-catenin pathway. Transforming growth factor-β promoted malignant biological behavior of pancreatic cancer cells through WNT/β-catenin pathway-dependent mechanism.

Conclusions
Our present study provided a novel mechanism involved in the inflammation-driven cancer progression through tumor immune escape and downstream gene regulation of WNT/β-catenin pathway-dependent manner.
Impact of Medicaid Expansion of the Affordable Care on the Outcomes of Lower Extremity Bypass for Patients With Peripheral Artery Disease in the Vascular Quality Initiative Database
Authors: Eslami Mohammad H. , Dakour-Aridi Hanaa , Avgerinos Efthymios D. , Makaroun Michel S. , Malas Mahmoud B. 
Published: August 2019

Objective:
The aim of this study was to evaluate changes in the utilization and outcomes of surgery after Medicaid Expansion (ME) for patients with peripheral artery disease (PAD).

Summary Background Data:
Recent studies have demonstrated increased insurance coverage and improved care with the Affordable Care Act's (ACA) state expansion of Medicaid.

Methods:
Infrainguinal bypass procedures performed due to occlusive pathology in the Vascular Quality Initiative database between 2010 and 2017 were included. Primary outcomes including postoperative mortality and major adverse limb events (MALE) at 1-year of follow-up were analyzed using interrupted time-series analysis (ITS).

Results:
Out of 26,446 infrainguinal bypass procedures, 13,955 (52.8%) were included in this analysis. ME states witnessed an annual decrease in infrainguinal surgery for acute ischemia [annual change in post vs pre-ME period (95% confidence interval): −4.3% (−7.5% to −1.0%), P = 0.02] and an increase in revascularization for claudication [3.7% (1.7%–5.6%), P = 0.01]. Among nonacute cases, elective procedures increased in ME states [3.9% (0.1%–7.7%), P = 0.05] along with a significant annual decrease in in-hospital mortality [−0.4% (−0.8 to −0.02), P = 0.04) and MALE at 1 year of follow up [−9.0% (−20.3 to 2.3), P = 0.09]. These results were statistically significant after comparing them with the annual trend changes in states which did not adopt ME.

Conclusions:
The adoption of ME in 2014 was associated with significant increase in the use of infrainguinal bypass for nonsevere and elective cases, along with improved in-hospital mortality and MALE at 1 year. Longer follow-up is needed to evaluate the impact of ME on other aspects of care and longer term outcomes of PAD patients.
Children with autism observe social interactions in an idiosyncratic manner
Authors: Avni Inbar , Meiri Gal , Bar-Sinai Asif , Reboh Doron , Manelis Liora , Flusser Hagit , Michaelovski Analya , Menashe Idan , Dinstein Ilan 
Published: August 2019

AbstractPrevious eye tracking studies have reported that children with autism spectrum disorders (ASD) fixate less on faces in comparison to controls. To properly understand social interactions, however, children must gaze not only at faces, but also at actions, gestures, body movements, contextual details, and objects, thereby creating specific gaze patterns when observing specific interactions. We presented three different movies of social interactions to 111 children (71 with ASD) who watched each of the movies twice. Typically developing children viewed the movies in a remarkably predictable and reproducible manner, exhibiting gaze patterns that were similar to the mean gaze pattern of other controls, with strong correlations across individuals (inter-subject correlations) and across movie presentations (intra-subject correlations). In contrast, children with ASD exhibited significantly more variable/idiosyncratic gaze patterns that differed from the mean gaze pattern of controls and were weakly correlated across individuals and presentations. Most importantly, quantification of gaze idiosyncrasy in individual children, enabled separation of ASD and control children with higher sensitivity and specificity than traditional measures such as time gazing at faces. Individual magnitudes of gaze idiosyncrasy were also significantly correlated with ASD severity and significantly correlated across movies and movie presentations, demonstrating their clinical sensitivity and reliability. These results suggest that gaze idiosyncrasy is a potent behavioral abnormality that characterizes many children with ASD and may contribute to their impaired social development. Quantification of gaze idiosyncrasy in individual children may aid in assessing their ASD severity over time and in response to treatments.Lay SummaryTypically developing children watch movies of social interactions in a reliable and predictable manner, attending faces, gestures, body movements, and objects that are relevant to the social interaction and its narrative. Here, we demonstrate that children with ASD watch such movies with significantly more variable/idiosyncratic gaze patterns that differ across individuals and across movie presentations. We demonstrate that quantifying this variability is a very potent way of identifying children with ASD and determining the severity of their social ASD symptoms.
Dynamic time-locking mechanism in the cortical representation of spoken words
Authors: Nora A. , Faisal A. , Seol J. , Renvall H. , Formisano E. , Salmelin R. 
Published: August 2019

AbstractHuman speech has a unique capacity to carry and communicate rich meanings. However, it is not known how the highly dynamic and variable perceptual signal is mapped to existing linguistic and semantic representations. In this novel approach, we utilized the natural acoustic variability of sounds and mapped them to magnetoencephalography (MEG) data using physiologically-inspired machine-learning models. We aimed at determining how well the models, differing in their representation of temporal information, serve to decode and reconstruct spoken words from MEG recordings in 16 healthy volunteers. We discovered that time-locking of the cortical activation to the unfolding speech input is crucial for the encoding of the acoustic-phonetic features. In contrast, time-locking was not highlighted in cortical processing of non-speech environmental sounds that conveyed the same meanings as the spoken words, including human-made sounds with temporal modulation content similar to speech. The amplitude envelope of the spoken words was particularly well reconstructed based on cortical evoked responses. Our results indicate that speech is encoded cortically with especially high temporal fidelity. This mechanism may contribute to the frequently reported entrainment of the cortical oscillations to the amplitude envelope of speech. Furthermore, the phoneme content was reflected in cortical evoked responses simultaneously with the spectrotemporal features, pointing to an instantaneous transformation of the unfolding acoustic features into linguistic representations during speech processing.Summary: Computational modeling of cortical responses to spoken words highlights the relevance of temporal tracking of spectrotemporal features, which is likely pivotal for transforming the acoustic-phonetic features into linguistic representations.