bluuebunny/crossref_metadata_2025_split huggingface dataset:
Organization and function of tension-dependent complexes at adherens junctions
Authors: Rauskolb Cordelia , Cervantes Estelle , Madere Ferralita , Irvine Kenneth D. 
Published: March 2019

ABSTRACT
Adherens junctions provide attachments between neighboring epithelial cells and a physical link to the cytoskeleton, which enables them to sense and transmit forces and to initiate biomechanical signaling. Examination of the Ajuba LIM protein Jub in Drosophila embryos revealed that it is recruited to adherens junctions in tissues experiencing high levels of myosin activity, and that the pattern of Jub recruitment varies depending upon how tension is organized. In cells with high junctional myosin, Jub is recruited to puncta near intercellular vertices, which are distinct from Ena-containing puncta, but can overlap Vinc-containing puncta. We identify roles for Jub in modulating tension and cellular organization, which are shared with the cytohesin Step, and the cytohesin adapter Sstn, and show that Jub and Sstn together recruit Step to adherens junctions under tension. Our observations establish Jub as a reporter of tension experienced at adherens junctions, and identify distinct types of tension-dependent and tension-independent junctional complexes. They also identify a role for Jub in mediating a feedback loop that modulates the distribution of tension and cellular organization in epithelia.
Distinct functions of a cGMP-dependent protein kinase in nerve terminal growth and synaptic vesicle cycling
Authors: Dason Jeffrey S. , Allen Aaron M. , Vasquez Oscar E. , Sokolowski Marla B. 
Published: March 2019

ABSTRACT
Sustained neurotransmission requires the tight coupling of synaptic vesicle (SV) exocytosis and endocytosis. The mechanisms underlying this coupling are poorly understood. We tested the hypothesis that a cGMP-dependent protein kinase (PKG), encoded by the foraging (for) gene in Drosophila melanogaster, is critical for this process using a for null mutant, genomic rescues and tissue-specific rescues. We uncoupled the exocytic and endocytic functions of FOR in neurotransmission using a temperature-sensitive shibire mutant in conjunction with fluorescein-assisted light inactivation of FOR. We discovered a dual role for presynaptic FOR, in which FOR inhibits SV exocytosis during low-frequency stimulation by negatively regulating presynaptic Ca2+ levels and maintains neurotransmission during high-frequency stimulation by facilitating SV endocytosis. Additionally, glial FOR negatively regulated nerve terminal growth through TGF-β signalling, and this developmental effect was independent of the effects of FOR on neurotransmission. Overall, FOR plays a critical role in coupling SV exocytosis and endocytosis, thereby balancing these two components to maintain sustained neurotransmission.
Behavioral responses of individual blue whales (Balaenoptera musculus) to mid-frequency military sonar
Authors: Southall Brandon L. , DeRuiter Stacy L. , Friedlaender Ari , Stimpert Alison K. , Goldbogen Jeremy A. , Hazen Elliott , Casey Caroline , Fregosi Selene , Cade David E. , Allen Ann N. , Harris Catriona M. , Schorr Greg , Moretti David , Guan Shane , Calambokidis John 
Published: March 2019

ABSTRACT
This study measured the degree of behavioral responses in blue whales (Balaenoptera musculus) to controlled noise exposure off the southern California coast. High-resolution movement and passive acoustic data were obtained from non-invasive archival tags (n=42) whereas surface positions were obtained with visual focal follows. Controlled exposure experiments (CEEs) were used to obtain direct behavioral measurements before, during and after simulated and operational military mid-frequency active sonar (MFAS), pseudorandom noise (PRN) and controls (no noise exposure). For a subset of deep-feeding animals (n=21), active acoustic measurements of prey were obtained and used as contextual covariates in response analyses. To investigate potential behavioral changes within individuals as a function of controlled noise exposure conditions, two parallel analyses of time-series data for selected behavioral parameters (e.g. diving, horizontal movement and feeding) were conducted. This included expert scoring of responses according to a specified behavioral severity rating paradigm and quantitative change-point analyses using Mahalanobis distance statistics. Both methods identified clear changes in some conditions. More than 50% of blue whales in deep-feeding states responded during CEEs, whereas no changes in behavior were identified in shallow-feeding blue whales. Overall, responses were generally brief, of low to moderate severity, and highly dependent on exposure context such as behavioral state, source-to-whale horizontal range and prey availability. Response probability did not follow a simple exposure–response model based on received exposure level. These results, in combination with additional analytical methods to investigate different aspects of potential responses within and among individuals, provide a comprehensive evaluation of how free-ranging blue whales responded to mid-frequency military sonar.
Large hospital variation in the utilization of Post-procedural CT to detect pulmonary embolism/Deep Vein Thrombosis in Patients Undergoing Total Knee or Hip Replacement Surgery: Japanese Nationwide Diagnosis Procedure Combination Database Study
Authors: Kumamaru Kanako K. , Kumamaru Hiraku , Yasunaga Hideo , Matsui Hiroki , Omiya Toshinobu , Hori Masaaki , Suzuki Michimasa , Wada Akihiko , Kamagata Koji , Takamura Tomohiro , Irie Ryusuke , Nakanishi Atsushi , Aoki Shigeki 
Published: March 2019

Objective:
The purpose of the study was to investigate variation in the use of in-hospital CT for venous thromboembolism (VTE) detection after total knee or hip replacement (TKR/THR) among surgical patients, using a nationwide Japanese in-hospital administrative database.

Methods:
This retrospective study using a national administrative database (4/2012–3/2013) extracted patients who underwent TKR/THR surgeries at hospitals meeting the annual case-volume threshold of ≥ 30. Hospitals were categorized into three equally sized groups by frequency of postoperative CT use (low, middle, and high CT use group) to compare baseline patient-level and hospital-level characteristics. To further investigate between-hospital variation in CT usage, we fitted a hierarchical logistic regression model including hospital-specific random intercepts and fixed patient- and hospital-level effects. The intra class correlation coefficient was used to measure the amount of variability in CT use attributable to between-hospital variation.

Results:
A total of 39,127 patients discharged from 447 hospitals met the inclusion criteria. The median hospital stay was 25 days (interquartile range, 20 – 32) and 7,599 (19.4%) patients underwent CT for VTE. CT utilization varied greatly among the hospitals; the crude frequency ranged from 0 to 100 % (median, 7.3 %; interquartile range, 1.8 – 18.3 %). After adjustment for known hospital- and patient-level factors related to CT use, 47 % of the variation in CT use remained attributable to the behavior of individual hospitals.

Conclusion:
We observed large inter hospital variability in the utilization of post-procedure CT for VTE detection in this Japanese TKR/THR cohort, suggesting that CT utilization is not optimized across the nation.

Advances in knowledge:
We observed significant variability in the utilization of post-procedure CT for VTE detection among inpatients who underwent TKR/THR surgeries in a large sample of Japanese hospitals. The large variation suggests that CT utilization is not optimized across the nation, and that there may be potential overutilization of the technology in the highest CT use hospitals.
Caucasian and south Asian men show equivalent improvements in surrogate biomarkers of cardiovascular and metabolic health following 6-weeks of supervised resistance training
Authors: Knox Allan , Sculthorpe Nicholas , Grace Fergal 
Published: March 2019

Background: The South Asian population have greater cardiovascular risk than their age-matched Caucasian counterparts, characterized by unfavorable biomarkers. South Asians may also be partially resistant to the pleiotropic benefits of physical activity on cardiovascular health. There is a current absence of studies that compare markers of cardio-metabolic health between Caucasians and South Asians employing resistance exercise. This study set out to compare the response in biomarkers of cardio-metabolic health in Caucasians and South Asians in response to resistance exercise.Methods: Caucasian (n=15, 25.5 ± 4.8 yrs) and South Asian (n=13, 25.4 ± 7.0 yrs) males completed a 6-week progressive resistance exercise protocol. Fasting blood glucose, insulin, and their product insulin resistance (HOMA-IR), triglycerides (TRIGS), low density lipoprotein (LDL), high density lipoprotein (HDL), total cholesterol (TC), vascular endothelial growth factor (VEGF), asymmetric dimythylarginine (ADMA), L-arginine (L-ARG) and C-reactive protein (CRP) were established at baseline and following resistance exercise.Results: There were significant improvements in fasting glucose, TC, LDL, HDL and VEGF in both groups following resistance exercise (p<0.05, for all). No change was observed in insulin, HOMA-IR, TRIGS, ADMA, L-ARG following resistance exercise (p>0.05, in both groups). CRP increased in the South Asian group (p<0.05) but not the Caucasian group (p>0.05)Conclusions: The cardio-metabolic response to resistance exercise is comparable in young Caucasian and South Asian males though inflammatory response to exercise may be prolonged in South Asians.
False signals induced by single-cell imputation
Authors: Andrews Tallulah S. , Hemberg Martin 
Published: March 2019

Background: Single-cell RNA-seq is a powerful tool for measuring gene expression at the resolution of individual cells. A challenge in the analysis of this data is the large amount of zero values, representing either missing data or no expression. Several imputation approaches have been proposed to address this issue, but they generally rely on structure inherent to the dataset under consideration they may not provide any additional information, hence, are limited by the information contained therein and the validity of their assumptions. Methods: We evaluated the risk of generating false positive or irreproducible differential expression when imputing data with six different methods. We applied each method to a variety of simulated datasets as well as to permuted real single-cell RNA-seq datasets and consider the number of false positive gene-gene correlations and differentially expressed genes. Using matched 10X and Smart-seq2 data we examined whether cell-type specific markers were reproducible across datasets derived from the same tissue before and after imputation. Results: The extent of false-positives introduced by imputation varied considerably by method. Data smoothing based methods, MAGIC, knn-smooth and dca, generated many false-positives in both real and simulated data. Model-based imputation methods typically generated fewer false-positives but this varied greatly depending on the diversity of cell-types in the sample. All imputation methods decreased the reproducibility of cell-type specific markers, although this could be mitigated by selecting markers with large effect size and significance. Conclusions: Imputation of single-cell RNA-seq data introduces circularity that can generate false-positive results. Thus, statistical tests applied to imputed data should be treated with care. Additional filtering by effect size can reduce but not fully eliminate these effects. Of the methods we considered, SAVER was the least likely to generate false or irreproducible results, thus should be favoured over alternatives if imputation is necessary.
Hub genes in a pan-cancer co-expression network show potential for predicting drug responses
Authors: Azuaje Francisco , Kaoma Tony , Jeanty Céline , Nazarov Petr V. , Muller Arnaud , Kim Sang-Yoon , Dittmar Gunnar , Golebiewska Anna , Niclou Simone P. 
Published: March 2019

Background: The topological analysis of networks extracted from different types of “omics” data is a useful strategy for characterizing biologically meaningful properties of the complex systems underlying these networks. In particular, the biological significance of highly connected genes in diverse molecular networks has been previously determined using data from several model organisms and phenotypes. Despite such insights, the predictive potential of candidate hubs in gene co-expression networks in the specific context of cancer-related drug experiments remains to be deeply investigated. The examination of such associations may offer opportunities for the accurate prediction of anticancer drug responses. Methods: Here, we address this problem by: a) analyzing a co-expression network obtained from thousands of cancer cell lines, b) detecting significant network hubs, and c) assessing their capacity to predict drug sensitivity using data from thousands of drug experiments. We investigated the prediction capability of those genes using a multiple linear regression model, independent datasets, comparisons with other models and our own in vitro experiments. Results: These analyses led to the identification of 47 hub genes, which are implicated in a diverse range of cancer-relevant processes and pathways. Overall, encouraging agreements between predicted and observed drug sensitivities were observed in public datasets, as well as in our in vitro validations for four glioblastoma cell lines and four drugs. To facilitate further research, we share our hub-based drug sensitivity prediction model as an online tool. Conclusions: Our research shows that co-expression network hubs are biologically interesting and exhibit potential for predicting drug responses in vitro. These findings motivate further investigations about the relevance and application of our unbiased discovery approach in pre-clinical, translationally-oriented research.
A study protocol for a randomised crossover study evaluating the effect of diets differing in carbohydrate quality on ileal content and appetite regulation in healthy humans
Authors: Byrne Claire S. , Blunt Dominic , Burn James , Chambers Edward , Dagbasi Aygul , Franco Becker Georgia , Gibson Glenn , Mendoza Lilian , Murphy Kevin , Poveda Carlos , Ramgulam Anya , Tashkova Martina , Walton Gemma , Washirasaksiri Chaiwat , Frost Gary 
Published: March 2019

Introduction: A major component of the digesta reaching the colon from the distal ileum is carbohydrate. This carbohydrate is subject to microbial fermentation and can radically change bacterial populations in the colon and the metabolites they produce, particularly short-chain fatty acids (SCFA). However, very little is currently known about the forms and levels of carbohydrate in the ileum and the composition of the ileal microbiota in humans. Most of our current understanding of carbohydrate that is not absorbed by the small intestine comes from ileostomy models, which may not reflect the physiology of an intact gastrointestinal tract. Methods: We will investigate how ileal content changes depending on diet using a randomised crossover study in healthy humans. Participants will be inpatients at the research facility for three separate 4-day visits. During each visit, participants will consume one of three diets, which differ in carbohydrate quality: 1) low-fibre refined diet; 2) high-fibre diet with intact cellular structures; 3) high-fibre diet where the cellular structures have been disrupted (e.g. milling, blending). On day 1, a nasoenteric tube will be placed into the distal ileum and its position confirmed under fluoroscopy. Ileal samples will be collected via the nasoenteric tube and metabolically profiled, which will determine the amount and type of carbohydrate present, and the composition of the ileal microbiota will be measured. Blood samples will be collected to assess circulating hormones and metabolites. Stool samples will be collected to assess faecal microbiota composition. Subjective appetite measures will be collected using visual analogue scales. Breath hydrogen will be measured in real-time as a marker of intestinal fermentation. Finally, an in vitro continuous fermentation model will be inoculated with ileal fluid in order to understand the shift in microbial composition and SCFA produced in the colon following the different diets. Registration: ISRCTN11327221.
Quantum of fluids in hospitalised patients with dengue fever and the presence of warning signs: a pilot cross-sectional study
Authors: Ramanathan Ramayee , Jain Dheeraj , Viswanathan Stalin 
Published: March 2019

Background: The World Health Organization in 2009 revised categories of dengue fever severity into classes A, B, and C based on the presence or absence of warning signs. The quantum of oral and intravenous fluids (IVF) in hospitalised patients with Group B (warning signs) have, to our knowledge, not been studied. Oral fluids in hospitalised patients and monitoring administration with the help of patients’ relatives have not been assessed. Methods: Consecutive patients with dengue fever and warning signs were studied for 48 hours after hospitalisation. Patients were asked to consume 4-5 l of fluids. Maintenance and bolus IVF were administered depending upon the presence of compensated or hypotensive shock. Intake and urinary output were monitored by the patient’s attendant. Total fluids (oral and intravenous) were divided by a number of anthropometric measurements. Significance of compensated and hypotensive shock, thrombocytopenia and 20% change in haematocrit, bleeding episodes and the need for transfusions, and organ impairment were considered in relation to the total amount of fluids received daily. Results: In total, 41 patients were studied. Patients with obesity and hypotensive shock received significantly more fluids on Day 1; taller patients and those with tachycardia, higher haematocrit and elevated creatine kinase correspondingly received more on Day 2. Hypotensive shock was significantly correlated with fluids/BSA and fluids/weight, while laboratory parameters correlated most strongly with fluids/BMI. Conclusions: Most adults with dengue and warning signs seem to require >100 ml/kg/day of fluids during their stay. Advising a similar amount of fluids at home during epidemics may further reduce the need for admissions. Participation of patients and their relatives in the bedside management of fluid administration may go a long way in preventing morbidity and mortality. Adults probably need a better anthropometric measurement to decide on the quantum of fluids to be given.
Life-cycle Analysis of Advanced Manure Management Systems for a Wisconsin Confined Animal Feeding Operation (CAFO)
Authors: Holzem Ryan M. , Katers John F. 
Published: March 2019

Abstract. Manure management is becoming an increasing burden for large dairy farms in Wisconsin and across the United States due to land application limitations for nutrients and hauling costs. One solution is to install advanced manure management systems, which remove large portions of water from the manure and treat it to a level sufficient for surface water discharge, livestock consumption, or irrigation. These systems can be divided into a pretreatment stage, which consists of solids removal, and a treatment stage, which generally consists of membranes. Not only does this approach reduce the quantity of material that is land applied, it can separate the nutrients into individual manure streams that can be more easily managed. However, there is still limited understanding regarding the costs and operation and maintenance requirements of these systems. To this end, a life-cycle analysis was completed for five commercially available advanced manure management systems based on how they would treat manure from a 3,500-cow dairy farm in Wisconsin, which was concerned only with the drawbacks of hauling and not application limitations. The evaluation included both an economic and non-economic analysis. The economic analysis consisted of a 20-year total present worth life-cycle cost analysis. The non-economic analysis consisted of a comparison of a set of non-economic factors that matched the management goals and strategies identified by the participating farm. Overall, all five systems evaluated addressed nutrient limitations and hauling costs. No treatment system had a payback less than 20 years at a hauling cost of $0.0040 L-1 ($0.015 gal-1). However, two systems had a payback period less than 20 years for a hauling cost of $0.0053 L-1 ($0.02 gal-1). Furthermore, if capital costs were ignored, the cost of recovered water was comparable to hauling costs for four of the alternatives. Still, there was high uncertainty in the estimated costs due to the low number of current installations of these systems on CAFOs. There was also a wide range of responses to the non-economic evaluation metrics, especially regarding performance, nutrient management techniques, chemical usage, and estimated regular operation and maintenance, which was again, likely due to the limited number of farm installations. Future work will verify actual costs and performance of these systems once implemented. Keywords: Advanced Manure Management, CAFOs, Dairy, Life-cycle analysis.