bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development of benchmark quality criteria for assessing whole‐endoscopy Barrett's esophagus biopsy cases
Authors: van der Wel MJ , Duits LC , Klaver E , Pouw RE , Seldenrijk CA , Offerhaus GJA , Visser M , ten Kate FJW , Tijssen JG , Bergman JJGHM , Meijer SL 
Published: March 2018

BackgroundDysplasia in Barrett's esophagus (BE) biopsies is associated with low observer agreement among general pathologists. Therefore, expert review is advised. We are developing a web‐based, national expert review panel for histological review of BE biopsies.ObjectiveThe aim of this study was to create benchmark quality criteria for future members.MethodsFive expert BE pathologists, with 10–30 years of BE experience, weekly handling 5–10 cases (25% dysplastic), assessed a case set of 60 digitalized cases, enriched for dysplasia. Each case contained all slides from one endoscopy (non‐dysplastic BE (NDBE), n = 21; low‐grade dysplasia (LGD), n = 20; high‐grade dysplasia (HGD), n = 19). All cases were randomized and assessed twice followed by group discussions to create a consensus diagnosis. Outcome measures: percentage of ‘indefinite for dysplasia’ (IND) diagnoses, intra‐observer agreement, and agreement with the consensus ‘gold standard’ diagnosis.ResultsMean percentage of IND diagnoses was 8% (3–14%) and mean intra‐observer agreement was 0.84 (0.66–1.02). Mean agreement with the consensus diagnosis was 90% (95% prediction interval (PI) 82–98%).ConclusionExpert pathology review of BE requires the scoring of a limited number of IND cases, consistency of assessment and a high agreement with a consensus gold standard diagnosis. These benchmark quality criteria will be used to assess the performance of other pathologists joining our panel.
Prompting arm activity after stroke: A clinical proof of concept study of wrist-worn accelerometers with a vibrating alert function
Authors: Da-Silva Ruth H , van Wijck Frederike , Shaw Lisa , Rodgers Helen , Balaam Madeline , Brkic Lianne , Ploetz Thomas , Jackson Dan , Ladha Karim , Price Christopher I 
Published: March 2018

Background Frequent practice of functional movements after stroke may optimise motor recovery; however, it is challenging for patients to remember to integrate an impaired limb into daily activities. We report the activity responses of stroke patients receiving a vibrating alert delivered by a tri-axial accelerometer wristband to prompt movement of the impaired arm if hourly activity levels fell. Methods Adults with upper limb impairment ≤28 days post-stroke wore the device for four weeks. Therapists and patients reviewed movement activity data twice weekly to agree ongoing rehabilitation activities and programme the wristband with a personalised prompt threshold (median baseline activity + 5%, 25% or 50%). Results: Seven patients completed the programme (five males; mean ± standard deviation (age) 64 ± 5 years; days post-stroke 13 ± 7; baseline/four-week Action Research Arm Test median (Interquartile range (IQR)) 39 (8, 44)/56 (11, 57)). Wristbands were worn for 89% of programme duration. A total of 1,288 prompts were delivered, with a median of four (IQR 3,7) prompts per patient per day. Mean activity increases following a prompt ranged from 11% to 29%. Conclusions Feedback delivered by a programmable accelerometer increased impaired arm activity. Improvements are required in device reliability before conducting a pragmatic clinical trial to examine the impact upon recovery.
Concussion Prevalence in Competitive Ultimate Frisbee Players
Authors: Lazar Damien J. , Lichtenstein Jonathan D. , Tybor David J. 
Published: March 2018

Background: Ultimate Frisbee (ultimate) is a fast-growing, popular sport played nationally by over 4 million athletes. While several studies have examined injury rates in ultimate, no work has investigated the prevalence of concussions specifically or players’ knowledge and management of those injuries. Purpose: To estimate the lifetime prevalence of concussions in ultimate and to assess players’ knowledge of concussions as well as their concussion management behaviors. Study Design: Descriptive epidemiology study. Methods: From June to November 2015, we collected ultimate-related concussion data via an anonymous web-based survey, the Concussion in Ultimate Frisbee Survey, from a convenience sample of 787 male and female ultimate players across the United States. Results: There were 553 male and 234 female respondents included in the analysis; 26.58% of men and 24.79% of women reported that they had sustained at least 1 concussion while playing ultimate, with 45.58% and 43.10% of those men and women, respectively, reporting multiple concussions. A total of 67.81% of men and 78.21% of women stated that they would remove themselves from play after sustaining a given concussion, although 45.99% of men and 37.62% of women indicated that they had returned to play in the same game or practice. Conclusion: Our preliminary data suggest that concussions do commonly occur in competitive ultimate and that better education and management of concussions in ultimate athletes are needed. This study is an important first step in deepening our understanding of these issues.
Identifying Successful Practices to Overcome Access to Care Challenges in Community Health Centers
Authors: Toscos Tammy , Carpenter Maria , Flanagan Mindy , Kunjan Kislaya , Doebbeling Bradley N. 
Published: March 2018

Background: Despite health care access challenges among underserved populations, patients, providers, and staff at community health clinics (CHCs) have developed practices to overcome limited access. These “positive deviant” practices translate into organizational policies to improve health care access and patient experience. Objective: To identify effective practices to improve access to health care for low-income, uninsured or underinsured, and minority adults and their families. Participants: Seven CHC systems, involving over 40 clinics, distributed across one midwestern state in the United States. Methods: Ninety-two key informants, comprised of CHC patients (42%) and clinic staff (53%), participated in semi-structured interviews. Interview transcripts were subjected to thematic analysis to identify patient-centered solutions for managing access challenges to primary care for underserved populations. Transcripts were coded using qualitative analytic software. Results: Practices to improve access to care included addressing illiteracy and low health literacy, identifying cost-effective resources, expanding care offerings, enhancing the patient–provider relationship, and cultivating a culture of teamwork and customer service. Helping patients find the least expensive options for transportation, insurance, and medication was the most compelling patient-centered strategy. Appointment reminders and confirmation of patient plans for transportation to appointments reduced no-show rates. Conclusion: We identified nearly 35 practices for improving health care access. These were all patient-centric, uncovered by both clinic staff and patients who had successfully navigated the health care system to improve access.
Establishment and long-term maintenance of primary intestinal epithelial cells cultured from the rainbow trout,Oncorhynchus mykiss
Authors: Langan Laura M. , Owen Stewart F. , Jha Awadhesh N. 
Published: March 2018

ABSTRACTA novel method for the establishment and long-term maintenance of ex vivo cultures from intestinal regions of the rainbow trout, Oncorhynchus mykiss (Walbaum), is reported. Adherence of cells was observed within hours, epithelial island formation recorded at 48 h and rapid proliferation with confluence achieved between 9-14 days. In addition to metabolic characterisation, basic morphology of growing cells was characterised using histology, immunofluorescence, transmission electron microscopy (TEM) and transepithelial electrical resistance (TEER). Regional differences in intestinal ethoxyresorufin-O-deethylase (EROD) and 7-ethoxycoumarin-O-deethylation (ECOD) activities in these primary grown enterocytes were compared following exposure to model inducers [i.e. α-NF, β-NF, B(a)P] which demonstrated significant differences. Regional differences in dietary uptake and metabolism of contaminants can therefore be studied in this in vitro system to increase our understanding of fundamental processes, while concurrently providing a means to reduce the number of fish required for biological studies in line with the principles of the 3Rs (Reduce, Refine and Replace).This article has an associated First Person interview with the first author of the paper.
Aquatic acidification: a mechanism underpinning maintained oxygen transport and performance in fish experiencing elevated carbon dioxide conditions
Authors: Hannan Kelly D. , Rummer Jodie L. 
Published: March 2018

ABSTRACT
Aquatic acidification, caused by elevating levels of atmospheric carbon dioxide (CO2), is increasing in both freshwater and marine ecosystems worldwide. However, few studies have examined how acidification will affect oxygen (O2) transport and, therefore, performance in fishes. Although data are generally lacking, the majority of fishes investigated in this meta-analysis exhibited no effect of elevated CO2 at the level of O2 uptake, suggesting that they are able to maintain metabolic performance during a period of acidosis. Notably, the mechanisms that fish employ to maintain performance and O2 uptake have yet to be verified. Here, we summarize current data related to one recently proposed mechanism underpinning the maintenance of O2 uptake during exposure to aquatic acidification, and reveal knowledge gaps that could be targeted for future research. Most studies have examined O2 uptake rates while fishes were resting and did not calculate aerobic scope, even though aerobic scope can aid in predicting changes to whole-animal metabolic performance. Furthermore, research is lacking on different age classes, freshwater species and elasmobranchs, all of which might be impacted by future acidification conditions. Finally, this Review further seeks to emphasize the importance of developing collaborative efforts between molecular, physiological and ecological approaches in order to provide more comprehensive predictions as to how future fish populations will be affected by climate change.
Nature's fat-burning machine: brown adipose tissue in a hibernating mammal
Authors: Ballinger Mallory A. , Andrews Matthew T. 
Published: March 2018

ABSTRACT
Brown adipose tissue (BAT) is a unique thermogenic tissue in mammals that rapidly produces heat via nonshivering thermogenesis. Small mammalian hibernators have evolved the greatest capacity for BAT because they use it to rewarm from hypothermic torpor numerous times throughout the hibernation season. Although hibernator BAT physiology has been investigated for decades, recent efforts have been directed toward understanding the molecular underpinnings of BAT regulation and function using a variety of methods, from mitochondrial functional assays to ‘omics’ approaches. As a result, the inner-workings of hibernator BAT are now being illuminated. In this Review, we discuss recent research progress that has identified players and pathways involved in brown adipocyte differentiation and maturation, as well as those involved in metabolic regulation. The unique phenotype of hibernation, and its reliance on BAT to generate heat to arouse mammals from torpor, has uncovered new molecular mechanisms and potential strategies for biomedical applications.
Drosophilaas a model to study obesity and metabolic disease
Authors: Musselman Laura Palanker , Kühnlein Ronald P. 
Published: March 2018

ABSTRACTExcess adipose fat accumulation, or obesity, is a growing problem worldwide in terms of both the rate of incidence and the severity of obesity-associated metabolic disease. Adipose tissue evolved in animals as a specialized dynamic lipid storage depot: adipose cells synthesize fat (a process called lipogenesis) when energy is plentiful and mobilize stored fat (a process called lipolysis) when energy is needed. When a disruption of lipid homeostasis favors increased fat synthesis and storage with little turnover owing to genetic predisposition, overnutrition or sedentary living, complications such as diabetes and cardiovascular disease are more likely to arise. The vinegar fly Drosophila melanogaster (Diptera: Drosophilidae) is used as a model to better understand the mechanisms governing fat metabolism and distribution. Flies offer a wealth of paradigms with which to study the regulation and physiological effects of fat accumulation. Obese flies accumulate triacylglycerols in the fat body, an organ similar to mammalian adipose tissue, which specializes in lipid storage and catabolism. Discoveries in Drosophila have ranged from endocrine hormones that control obesity to subcellular mechanisms that regulate lipogenesis and lipolysis, many of which are evolutionarily conserved. Furthermore, obese flies exhibit pathophysiological complications, including hyperglycemia, reduced longevity and cardiovascular function – similar to those observed in obese humans. Here, we review some of the salient features of the fly that enable researchers to study the contributions of feeding, absorption, distribution and the metabolism of lipids to systemic physiology.
Non-adrenergic control of lipolysis and thermogenesis in adipose tissues
Authors: Braun Katharina , Oeckl Josef , Westermeier Julia , Li Yongguo , Klingenspor Martin 
Published: March 2018

ABSTRACT
The enormous plasticity of adipose tissues, to rapidly adapt to altered physiological states of energy demand, is under neuronal and endocrine control. In energy balance, lipolysis of triacylglycerols and re-esterification of free fatty acids are opposing processes operating in parallel at identical rates, thus allowing a more dynamic transition from anabolism to catabolism, and vice versa. In response to alterations in the state of energy balance, one of the two processes predominates, enabling the efficient mobilization or storage of energy in a negative or positive energy balance, respectively. The release of noradrenaline from the sympathetic nervous system activates lipolysis in a depot-specific manner by initiating the canonical adrenergic receptor–Gs-protein–adenylyl cyclase–cyclic adenosine monophosphate–protein kinase A pathway, targeting proteins of the lipolytic machinery associated with the interface of the lipid droplets. In brown and brite adipocytes, lipolysis stimulated by this signaling pathway is a prerequisite for the activation of non-shivering thermogenesis. Free fatty acids released by lipolysis are direct activators of uncoupling protein 1-mediated leak respiration. Thus, pro- and anti-lipolytic mediators are bona fide modulators of thermogenesis in brown and brite adipocytes. In this Review, we discuss adrenergic and non-adrenergic mechanisms controlling lipolysis and thermogenesis and provide a comprehensive overview of pro- and anti-lipolytic mediators.
Obese super athletes: fat-fueled migration in birds and bats
Authors: Guglielmo Christopher G. 
Published: March 2018

ABSTRACTMigratory birds are physiologically specialized to accumulate massive fat stores (up to 50–60% of body mass), and to transport and oxidize fatty acids at very high rates to sustain flight for many hours or days. Target gene, protein and enzyme analyses and recent -omic studies of bird flight muscles confirm that high capacities for fatty acid uptake, cytosolic transport, and oxidation are consistent features that make fat-fueled migration possible. Augmented circulatory transport by lipoproteins is suggested by field data but has not been experimentally verified. Migratory bats have high aerobic capacity and fatty acid oxidation potential; however, endurance flight fueled by adipose-stored fat has not been demonstrated. Patterns of fattening and expression of muscle fatty acid transporters are inconsistent, and bats may partially fuel migratory flight with ingested nutrients. Changes in energy intake, digestive capacity, liver lipid metabolism and body temperature regulation may contribute to migratory fattening. Although control of appetite is similar in birds and mammals, neuroendocrine mechanisms regulating seasonal changes in fuel store set-points in migrants remain poorly understood. Triacylglycerol of birds and bats contains mostly 16 and 18 carbon fatty acids with variable amounts of 18:2n-6 and 18:3n-3 depending on diet. Unsaturation of fat converges near 70% during migration, and unsaturated fatty acids are preferentially mobilized and oxidized, making them good fuel. Twenty and 22 carbon n-3 and n-6 polyunsaturated fatty acids (PUFA) may affect membrane function and peroxisome proliferator-activated receptor signaling. However, evidence for dietary PUFA as doping agents in migratory birds is equivocal and requires further study.
The effect of diet and exercise on lipid droplet dynamics in human muscle tissue
Authors: Daemen Sabine , van Polanen Nynke , Hesselink Matthijs K. C. 
Published: March 2018

ABSTRACTThe majority of fat in the human body is stored as triacylglycerols in white adipose tissue. In the obese state, adipose tissue mass expands and excess lipids are stored in non-adipose tissues, such as skeletal muscle. Lipids are stored in skeletal muscle in the form of small lipid droplets. Although originally viewed as dull organelles that simply store lipids as a consequence of lipid overflow from adipose tissue, lipid droplets are now recognized as key components in the cell that exert a variety of relevant functions in multiple tissues (including muscle). Here, we review the effect of diet and exercise interventions on myocellular lipid droplets and their putative role in insulin sensitivity from a human perspective. We also provide an overview of lipid droplet biology and identify gaps for future research.
The evolution of body fatness: trading off disease and predation risk
Authors: Speakman John R. 
Published: March 2018

ABSTRACT
Human obesity has a large genetic component, yet has many serious negative consequences. How this state of affairs has evolved has generated wide debate. The thrifty gene hypothesis was the first attempt to explain obesity as a consequence of adaptive responses to an ancient environment that in modern society become disadvantageous. The idea is that genes (or more precisely, alleles) predisposing to obesity may have been selected for by repeated exposure to famines. However, this idea has many flaws: for instance, selection of the supposed magnitude over the duration of human evolution would fix any thrifty alleles (famines kill the old and young, not the obese) and there is no evidence that hunter-gatherer populations become obese between famines. An alternative idea (called thrifty late) is that selection in famines has only happened since the agricultural revolution. However, this is inconsistent with the absence of strong signatures of selection at single nucleotide polymorphisms linked to obesity. In parallel to discussions about the origin of obesity, there has been much debate regarding the regulation of body weight. There are three basic models: the set-point, settling point and dual-intervention point models. Selection might act against low and high levels of adiposity because food unpredictability and the risk of starvation selects against low adiposity whereas the risk of predation selects against high adiposity. Although evidence for the latter is quite strong, evidence for the former is relatively weak. The release from predation ∼2-million years ago is suggested to have led to the upper intervention point drifting in evolutionary time, leading to the modern distribution of obesity: the drifty gene hypothesis. Recent critiques of the dual-intervention point/drifty gene idea are flawed and inconsistent with known aspects of energy balance physiology. Here, I present a new formulation of the dual-intervention point model. This model includes the novel suggestion that food unpredictability and starvation are insignificant factors driving fat storage, and that the main force driving up fat storage is the risk of disease and the need to survive periods of pathogen-induced anorexia. This model shows why two independent intervention points are more likely to evolve than a single set point. The molecular basis of the lower intervention point is likely based around the leptin pathway signalling. Determining the molecular basis of the upper intervention point is a crucial key target for future obesity research. A potential definitive test to separate the different models is also described.
Insights into brown adipose tissue evolution and function from non-model organisms
Authors: Jastroch Martin , Oelkrug Rebecca , Keipert Susanne 
Published: March 2018

ABSTRACT
Brown adipose tissue (BAT) enables adaptive thermoregulation through heat production that is catalyzed by mitochondrial uncoupling protein 1 (UCP1). BAT is frequently studied in rodent model organisms, and recently in adult humans to treat metabolic diseases. However, complementary studies of many non-model species, which have diversified to many more ecological niches, may significantly broaden our understanding of BAT regulation and its physiological roles. This Review highlights the research on non-model organisms, which was instrumental to the discovery of BAT function, and the unique evolutionary history of BAT/UCP1 in mammalian thermogenesis. The comparative biology of BAT provides a powerful integrative approach that could identify conserved and specialized functional changes in BAT and UCP1 by considering species diversity, ecology and evolution, and by fusing multiple scientific disciplines such as physiology and biochemistry. Thus, resolving the complete picture of BAT biology may fail if comparative studies of non-model organisms are neglected.
The Chlamydia muridarum plasmid revisited : new insights into growth kinetics
Authors: Skilton Rachel J. , Wang Yibing , O'Neill Colette , Filardo Simone , Marsh Peter , Bénard Angèle , Thomson Nicholas R. , Ramsey Kyle H. , Clarke Ian N. 
Published: March 2018

Background:Research in chlamydial genetics is challenging because of its obligate intracellular developmental cycle.In vivosystems exist that allow studies of different aspects of basic biology of chlamydiae, the murineChlamydia muridarummodel is one of great importance and thus an essential research tool.C. muridarumcarries a plasmid that has a role in virulence. Our aim was to compare and contrast theC. muridarumplasmid-free phenotype with that of a chromosomally isogenic plasmid-bearing strain, through the inclusion phase of the developmental cycle.Methods:We measured infectivity for plasmid bearing and plasmid-curedC. muridarumby inclusion forming assays in McCoy cells and in parallel bacterial chromosome replication by quantitative PCR, throughout the developmental cycle. In addition to these studies, we have carefully monitored chlamydial inclusion formation by confocal microscopy and transmission electron microscopy. A newE.coli/chlamydial shuttle vector (pNigg::GFP) was constructed using standard cloning technology and used to transformC. muridarumfor further phenotypic studies.Results:We have advanced the definition of the chlamydial phenotype away from the simple static observation of mature inclusions and redefined theC. muridarumplasmid-based phenotype on growth profile and inclusion morphology. Our observations on the growth properties of plasmid-curedC. muridarumchallenge the established interpretations, especially with regard to inclusion growth kinetics. Introduction of the shuttle plasmid pNigg::GFP into plasmid-curedC. muridarumrestored the wild-type plasmid-bearing phenotype and confirmed that loss of the plasmid was the sole cause for the changes in growth and chromosomal replication.Conclusions:Accurate growth curves and sampling at multiple time points throughout the developmental cycle is necessary to define plasmid phenotypes. There are subtle but important (previously unnoticed) differences in the overall growth profile of plasmid-bearing and plasmid-freeC. muridarum. We have proven that the differences described are solely due to the plasmid pNigg.