bluuebunny/crossref_metadata_2025 huggingface dataset:
Crossbreeding effects on growth and efficiency in beef cow–calf systems: evaluation of Angus, Caracu, Hereford and Nelore breed direct, maternal and heterosis effects
Authors: Mendonça Fábio S , MacNeil Michael D , Leal Willian S , Azambuja Rodrigo C C , Rodrigues Pedro F , Cardoso Fernando F
Published: August 2019

The objective of this study was to determine breed additive and heterosis effects on growth curves, total milk yield (TMY), calf weaning weight (WW), predicted energy intake (EI), and cow efficiency (CE) of purebred and crossbred beef cows raised in Southern Brazil. The data were from 175 purebred and crossbred cows representing eight genetic groups: Angus (A), Hereford (H), Nelore (N), A × H (AH), H × A (HA), A × N (AN), N × A (NA), and Caracu (C) × A (CA). Growth of the cows was modeled using the nonlinear Brody function and machine milking was used to assess TMY. WW was linearly adjusted to 210 d. EI was predicted with an equation in which the independent variables were estimates of parameters of the Brody function and TMY. The ratio of WW to EI estimated CE. Taurine–indicine heterosis effects were significant for all traits, and greater than those for taurine breed crosses. In general, crossbred cows were heavier at maturity, matured earlier, produced more milk, weaned heavier calves, and were predicted to consume more energy. Thus, they were more efficient than purebred cows, despite their greater predicted feed intake. Among the purebreds, A cows matured most rapidly, weighed the least at maturity, produced the most milk, weaned the heaviest calves, were predicted to consume the least energy; and were therefore most efficient among the breeds that were evaluated. These results are useful as inputs to bioeconomic models that can be used to predict productive and economic outcomes from crossbreeding and to facilitate recommendations for beef producers of southern Brazil and other similar subtropical climatic regions.
Genome Resource of Barley Bacterial Blight and Leaf Streak Pathogen Xanthomonas translucens pv. translucens strain UPB886
Authors: Roman-Reyna Verónica , Luna Emily K. , Pesce Céline , Vancheva Taca , Chang Christine , Ziegle Janet , Bragard Claude , Koebnik Ralf , Lang Jillian M. , Leach Jan E. , Jacobs Jonathan M.
Published: August 2019

Xanthomonas translucens pv. translucens causes bacterial leaf streak and bacterial blight diseases of barley. This pathogen limits barley production globally but remains understudied, with limited genomic resources. To better understand the biology of this X. translucens subgroup, we sequenced the complete genome of the X. translucens pv. translucens strain UPB886.
Setting Yourself Up for Success: Locked Plating in Periprosthetic Fractures About Total Knee Arthroplasty
Authors: Pires Robinson E. , Kfuri Mauricio
Published: August 2019

As the incidence of total knee arthroplasty increases, a concurrent increase in periprosthetic fractures will also occur. This article focuses on the most common fracture types and current strategies adopted to overcome this challenging clinical problem. Our goal is to outline the role of locking plates in the management of knee periprosthetic fractures.
Setting Yourself Up for Success: Retrograde Intramedullary Nailing in Periprosthetic Fractures About Total Knee Arthroplasty
Authors: Medda Suman , Snoap Tyler , Carroll Eben A.
Published: August 2019

Treatment of periprosthetic fractures above total knee arthroplasty remains challenging because of assessment of implant stability and the short segment of often osteoporotic bone available for distal fixation. Fractures with significant medial comminution should undergo retrograde intramedullary nailing or dual-implant fixation, as isolated lateral locked plating is not indicated. There are a multitude of objective and subjective factors incorporated into the decision to proceed with retrograde nailing including assessment of the patient's functional status, fracture morphology, implant stability, and compatibility of the prosthesis with retrograde nailing. Here, we review the steps to success in using retrograde intramedullary nailing in the treatment of specific periprosthetic fractures about total knee arthroplasty.
Periprosthetic Femur Fractures Around a Loose Femoral Stem
Authors: Rozell Joshua C. , Donegan Derek J.
Published: August 2019

A critical component in the evaluation of a patient with a periprosthetic hip fracture is determination of stem stability. Failure to critically evaluate preoperative radiographs and subsequently intraoperative stem position may result in an incorrect treatment algorithm and early catastrophic failure of the implant construct. In 2018, this is becoming a larger issue as demand for revision total hip arthroplasty increases. Several factors contribute to the type of implant used in these fractures and depend on age, activity level, comorbidities, and available bone stock. The purpose of this article is to review the evaluation of periprosthetic hip fractures around a loose stem and provide tips and tricks for their management to allow for a successful, long-lasting outcome.
Consensus on Implants in Infections After Spine Surgery
Authors: Divi Srikanth N. , Kepler Christopher K. , Boody Barrett S. , Bronson Wesley H. , Russo Glenn S. , Segar Anand H. , Galetta Matthew S. , Goyal Dhruv K.C. , Fang Taolin , Schroeder Gregory D. , Vaccaro Alexander R.
Published: August 2019

In July of 2018, the Second International Consensus Meeting (ICM) on Musculoskeletal Infection convened in Philadelphia, PA was held to discuss issues regarding infection in orthopedic patients and to provide consensus recommendations on these issues to practicing orthopedic surgeons. During this meeting, attending delegates divided into subspecialty groups to discuss topics specifics to their respective fields, which included the spine. At the spine subspecialty group meeting, delegates discussed and voted upon the recommendations for 63 questions regarding the prevention, diagnosis, and treatment of infection in spinal surgery. Of the 63 questions, 9 focused on implants questions in spine surgery, for which this article provides the recommendations, voting results, and rationales.
Understanding Complex Roles of Family for Latina Health
Authors: Molina Yamilé , Henderson Vida , Ornelas India J. , Scheel John R. , Bishop Sonia , Doty Sarah L. , Patrick Donald L. , Beresford Shirley A. A. , Coronado Gloria D.
Published: August 2019

We developed a measure of family obligation stress and compared its relationship to health and unmet health care needs relative to social support among a sample of US-based Latinas. Data come from a randomized controlled trial within 4 clinics to increase mammography among Latinas (n = 539). The 1-factor measure had acceptable reliability and construct validity. Family obligation stress was associated with worse health and greater unmet health care needs. Family obligation stress varied by years in the United States and country of origin. Our measure of family obligation stress contributes new venues to family research among Latino populations.
Home Food Environment Factors Associated With Hispanic Preschoolers' Intake of Fruits and Vegetables
Authors: Lora Karina R. , Branscum Paul W. , Chen Sixia , Wakefield Dorothy
Published: August 2019

The purpose of this study was to evaluate the relationship of home fruit and vegetable (F&V) availability and maternal feeding practices with Hispanic preschoolers' F&V intake (N = 238). “Availability' of total fruit” (P < .0001) and “modeling” (P < .020) increased the odds of consuming 1 or more cups of fruit. “Pressure” (P < .009) and the child being female (P < .028) increased the odds of consuming 1 or more cups of vegetables, while having a greater number of children in the home (P < .037) reduced the odds of consuming 1 or more cups of vegetables. To increase preschoolers' intake of F&V, interventions should target specific environmental factors in the home and maternal monitoring practices.
ABRUPTLY EMERGING VESSELS IN EYES WITH MYOPIC PATCHY CHORIORETINAL ATROPHY
Authors: Xie Shiqi , Fang Yuxin , Du Ran , Yokoi Tae , Takahashi Hiroyuki , Uramoto Kengo , Yoshida Takeshi , Ohno-Matsui Kyoko
Published: August 2019

Purpose:

To determine the prevalence and characteristics of abruptly emerging vessels (AEVs) within patchy atrophy (PA) in myopic eyes.

Methods:

We studied 160 highly myopic eyes of 144 patients between March and November in 2016. Fundus photographs and swept-source optical coherence tomography images were analyzed.

Results:

Patient mean age was 67.1 ± 10.5 years. Mean axial length was 30.9 ± 2.0 mm. The mean size of the 264 PAs was 5.6 ± 8.3 mm2. Abruptly emerging vessels were detected in 69 (43.1%) eyes and were located within or near PA edge in fundus photographs. Swept-source optical coherence tomography showed that the AEVs were continuous with perforating scleral vessels and were observed on the inner surface of the sclera at the site where they appeared in fundus photographs. A slight bowing of sclera around the AEVs was observed in 41 (59%) eyes. Patchy atrophy with AEVs was significantly larger (10.7 ± 11.3 mm2) than PA without AEVs (3.4 ± 5.1 mm2).

Conclusion:

Abruptly emerging vessels are commonly found in eyes with myopic PA. The sclera surrounding the AEVs is slightly bowed. Further studies are needed to determine whether the penetrating site of AEVs is structurally more fragile and leads to Bruch membrane defects or AEVs are secondarily involved during PA progression.
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.
Specific Histopathologic Features Aid in Distinguishing Diffuse-type Gastric Adenocarcinoma From Metastatic Lobular Breast Carcinoma
Authors: Clinton Lani K. , Plesec Thomas , Goldblum John R. , Hajifathalian Kaveh , Downs-Kelly Erinn , Patil Deepa T.
Published: August 2019

Metastatic invasive lobular carcinoma (mILC) may masquerade as primary diffuse gastric adenocarcinoma (PDGA) by demonstrating significant clinical and pathologic overlap. Accurate distinction is of therapeutic and prognostic significance. On the basis of anecdotal cases of mILC that lacked estrogen receptor and/or GATA3 expression, we analyzed the cytoarchitectural features of 28 mILC and 44 PDGA specimens obtained from women to assess features that would help in this distinction and prompt ancillary work-up. In addition to performing an interobserver agreement analysis among 3 pathologists, we also evaluated SATB2 expression in this setting. Eighteen of 20 (90%) patients had a history of ILC. The mean interval between initial diagnosis of breast cancer and metastasis was 7.3 years (range: 1 to 36 y). Compared with mILC, PDGA was significantly associated with full-thickness mucosal involvement (47% vs. 80%; P=0.015), a nested/sheet-like growth pattern (32% vs. 68%; P=0.004), anastomosing cords (0% vs. 100%; P=0.001), multivacuolated cells (0% vs. 61%; P<0.0001), pleomorphic nuclei (4% vs. 70%; P<0.0001) and enlarged nuclei (4% vs. 70%; P<0.0001). Single file growth pattern (P<0.0001) and superficial lamina propria involvement (P=0.009) were more common in mILC. Estrogen receptor and GATA3 were expressed in all but 5 mILC cases; SATB2 was only seen in 30% of PDGA cases. Our results demonstrate that in a biopsy specimen, careful morphologic assessment can be extremely helpful in distinguishing mILC from PDGA and guiding ancillary work-up, especially when a history of breast cancer may not be readily available or when the neoplasm lacks expression of conventional breast markers.
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

Previous 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 Summary

Typically 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

Human 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.
Applications of a Novel Knowledge Discovery and Data Mining Process Model for Metabolomics
Authors: BaniMustafa Ahmed , Hardy Nigel
Published: August 2019

ABSTRACT

This work demonstrates the execution of a novel process model for knowledge discovery and data mining for metabolomics (MeKDDaM). It aims to illustrate MeKDDaM process model applicability using four different real-world applications and to highlight its strengths and unique features. The demonstrated applications provide coverage for metabolite profiling, target analysis, and metabolic fingerprinting. The data analysed in these applications were captured by chromatographic separation and mass spectrometry technique (LC-MS), Fourier transform infrared spectroscopy (FT-IR), and nuclear magnetic resonance spectroscopy (NMR) and involve the analysis of plant, animal, and human samples. The process was executed using both data-driven and hypothesis-driven data mining approaches in order to perform various data mining goals and tasks by applying a number of data mining techniques. The applications were selected to achieve a range of analytical goals and research questions and to provide coverage for metabolite profiling, target analysis, and metabolic fingerprinting using datasets that were captured by NMR, LC-MS, and FT-IR using samples of a plant, animal, and human origin. The process was applied using an implementation environment which was created in order to provide a computer-aided realisation of the process model execution.
Anatomical development of the cerebellothalamic tract in embryonic mice
Authors: Dumas Daniël B. , Gornati Simona V. , Adolfs Youri , Shimogori Tomomi , Pasterkamp R. Jeroen , Hoebeek Freek E.
Published: August 2019

Cerebellar projections to the thalamus are a pivotal connection in cerebello-cerebral interactions. Apart from its role in coordinating sensorimotor integration in the adult brain, the cerebello-thalamic projection has also been implemented in developmental disorders, such as autism spectrum disorders. Although the development of the cerebellum, thalamus and cerebral cortex have been studied in many species, a detailed description of the ontogeny of the mammalian cerebello-thalamic tract (CbT) is currently missing. Here we investigated the development of the CbT at embryonic stages using transgenic Ntsr1-Cre/Ai14 mice and in utero electroporation (IUE) of wild type mice. Wide-field, confocal and 3D light-sheet imaging of immunohistochemical stainings showed that CbT fibers arrive in the prethalamus between E14.5 and E15.5, but only invade the thalamus after E16.5. We quantified the spread of CbT fibers throughout the various thalamic nuclei and found that at E17.5 and E18.5 the ventrolateral, ventromedial and parafascicular nuclei, but also the mediodorsal and posterior complex become increasingly innervated. Several CbT fiber varicosities colocalize with vGluT2, indicating that already from E18.5 the CbT synapse in various thalamic nuclei. Our results contribute to the construction of a frame of reference on the anatomical development of the CbT, which will help to guide future experiments investigating neurodevelopmental disorders.

Significance statement

Using various microscopic approaches, we investigated the anatomical development of the fiber tract between the cerebellum and thalamus, one of the major mammalian brain connections. Our results show that in mice cerebellar axons wait outside of the thalamus from embryonic day (E)15.5 until E17.5 before invading the thalamic complex. Cerebellar axons establish vGluT2-positive synapses at E18.5 throughout various thalamic nuclei, each of which subsequently develops its connections with dedicated cerebral cortical regions. Our data thereby advocate the cerebellar influence on the maturation of the thalamus and connected cerebral cortex. This knowledge can help to guide future experiments into neurodevelopmental disorders affecting cerebello-thalamo-cortical networks.
Degradation of the incretin hormone Glucagon-Like Peptide-1 (GLP-1) byEnterococcus faecalismetalloprotease GelE
Authors: LeValley Stephanie L. , Tomaro-Duchesneau Catherine , Britton Robert A.
Published: August 2019

Metabolic diseases, including Type 2 Diabetes and obesity, have become increasingly prevalent global health concerns. Studies over the past decade have established connections between the gastrointestinal microbiota and host metabolism, but the mechanisms behind these connections are only beginning to be understood. We were interested in identifying microbes that have the ability to modulate the levels of the incretin hormone glucagon like peptide 1 (GLP-1). Using a human derived cell line that is capable of secreting GLP-1 in response to stimulatory ligands (NCI-H716), we identified supernatants from several bacterial isolates that were capable of decreasing GLP-1 levels, including several strains ofEnterococcus faecalis. We further identified the secreted protease GelE, an established virulence factor fromE. faecalis, as being responsible for GLP-1 inhibition via direct cleavage of GLP-1 by GelE. Finally, we demonstrated thatE. faecalissupernatants can disrupt a colonic epithelial monolayer and cleave GLP-1 in agelEdependent manner. This work suggests that a secreted factor from an intestinal microbe can traverse the epithelial barrier and impact levels of an important intestinal hormone.

Importance

Humans have a complex and interconnected relationship with their gastrointestinal microbiomes, yet our interest in the microbiome tends to focus on overt pathogenic or probiotic activities, leaving the roles that commensal species may have on host physiology and metabolic processes largely unexplored. Commensal organisms in the microbiome produce and secrete many factors that have an opportunity to interact with the gastrointestinal tract and host biology. Here we show that a secreted protease fromE. faecalis, GelE, is able to degrade the gastrointestinal hormone GLP-1, which is responsible for regulating glucose homeostasis and appetite in the body. The disruption of natural GLP-1 signaling by GelE may have significant consequences for maintaining healthy blood glucose levels and in the development of metabolic disease. Furthermore, this work deepens our understanding of specific host-microbiome interactions.
N-Acetyl Cysteine Alleviates Coxsackievirus B-Induced Myocarditis by Suppressing caspase-1
Authors: Wang Yao , Zhao Shuoxuan , Chen Yang , Wang Ying , Wang Tianying , Wo Xiaoman , Dong Yanyan , Zhang Jian , Xu Weizhen , Qu Cong , Feng Xiaofeng , Wu Xiaoyu , Wang Yan , Zhong Zhaohua , Zhao Wanran
Published: August 2019

Viral myocarditis caused by Coxsackievirus B (CVB) infection is a severe inflammatory disease of the myocardium, which may develop to cardiomyopathy and heart failure. No effective medicine is available to treat CVB infection. Here we evaluated the anti-CVB effect of N-acetyl cysteine (NAC), a widely used antioxidant. NAC significantly alleviated myocarditis and improved the overall condition of CVB type 3 (CVB3)-infected mice. Importantly, NAC treatment suppressed viral replication in both myocardium and cell culture. We show that NAC inhibited CVB3 replication when it was applied at the early stage of CVB3 infection. NAC’s antiviral mechanism, while independent of its antioxidant property, relies on its inhibition on caspase-1 activation, since the knockdown of caspase-1 blocked CVB3 replication. Moreover, NAC promotes procaspase-1 degradation via ubiquitin proteasome system, which may further contribute to the inhibited activity of caspase-1. NAC also inhibits the activity of viral proteases. Taken together, this study shows that NAC exerts potent anti-CVB effect by inhibiting caspase-1 and viral proteases. This study suggests that NAC can be a safe therapeutic option for CVB-induced myocarditis.
Polygenic patterns of adaptive introgression in modern humans are mainly shaped by response to pathogens
Authors: Gouy Alexandre , Excoffier Laurent
Published: August 2019

Anatomically modern humans carry many introgressed variants from other hominins in their genomes. Some of them affect their phenotype and can thus be negatively or positively selected. Several individual genes have been proposed to be the subject of adaptive introgression, but the possibility of polygenic adaptive introgression has not been extensively investigated yet. In this study, we analyze archaic introgression maps with refined functional enrichment methods to find signals of polygenic adaptation of introgressed variants. We first apply a method to detect sets of connected genes (sub-networks) within biological pathways that present higher-than-expected levels of archaic introgression. We then introduce and apply a new statistical test to distinguish between epistatic and independent selection in gene sets of present-day humans. We identify several known targets of adaptive introgression, and we show that they belong to larger networks of introgressed genes. After correction for genetic linkage, we find that signals of polygenic adaptation are mostly explained by independent and potentially sequential selection episodes. However, we also find some gene sets where introgressed variants present significant signals of epistatic selection. Our results confirm that archaic introgression has facilitated local adaptation, especially in immunity-related and metabolic functions and highlight its involvement in a coordinated response to pathogens out of Africa.
Why is interoperability between the two fields of chemical crystallography and protein crystallography so difficult?
Authors: Brink Alice , Helliwell John R.
Published: August 2019

The interoperability of chemical and biological crystallographic data is a key challenge to research and its application to pharmaceutical design. Research attempting to combine data from the two disciplines, small-molecule or chemical crystallography (CX) and macromolecular crystallography (MX), will face unique challenges including variations in terminology, software development, file format and databases which differ significantly from CX to MX. This perspective overview spans the two disciplines and originated from the investigation of protein binding to model radiopharmaceuticals. The opportunities of interlinked research while utilizing the two databases of the CSD (Cambridge Structural Database) and the PDB (Protein Data Bank) will be highlighted. The advantages of software that can handle multiple file formats and the circuitous route to convert organometallic small-molecule structural data for use in protein refinement software will be discussed. In addition some pointers to avoid being shipwrecked will be shared, such as the care which must be taken when interpreting data precision involving small molecules versus proteins.
Algorithm for distance list extraction from pair distribution functions
Authors: Gu Ran , Banerjee Soham , Du Qiang , Billinge Simon J. L.
Published: August 2019

An algorithm is presented to extract the distance list from atomic pair distribution functions in a highly automated way. The algorithm is constructed via curve fitting based on a Debye scattering equation model. Because of the non-convex nature of the resulting optimization problem, a number of techniques are developed to overcome various computational difficulties. A key ingredient is a new approach to obtain a reasonable initial guess based on the theoretical properties of the mathematical model. Tests on various nanostructured samples show the effectiveness of the initial guess and the accuracy and overall good performance of the extraction algorithm. This approach could be extended to any spectrum that is approximated as a sum of Gaussian functions.