bluuebunny/crossref_metadata_2025_split huggingface dataset:
Liver injury is most commonly due to hepatic metastases rather than drug hepatotoxicity during pembrolizumab immunotherapy
Authors: Tsung Irene , Dolan Russell , Lao Christopher D. , Fecher Leslie , Riggenbach Kane , Yeboah‐Korang Amoah , Fontana Robert J. 
Published: July 2019

SummaryBackgroundPembrolizumab immunotherapy has been associated with hepatotoxicity in 1%‐10% of oncology patients treated in clinical trials.AimTo describe the incidence, phenotypes and outcomes of liver injury in a large cohort of solid organ tumour patients receiving pembrolizumabMethodsLiver injury was defined by serum alanine aminotransferase, alkaline phosphatase, and/or total bilirubin levels exceeding threshold values. The likelihood of drug‐induced liver injury was adjudicated by expert opinion.ResultsSeventy (14.3%) of the 491 pembrolizumab‐treated patients developed liver injury at a median of 62 days (6‐478) and 71.4% had a cholestatic injury profile at onset. The median age, gender and tumour types of liver injury patients were similar to those without, but hepatic metastases (53% vs 21%, P < 0.01) and prior systemic and liver‐directed therapy (71% vs 53%, P < 0.01) were more commonly observed in liver injury patients. During follow‐up, liver injury patients were less likely to experience tumour remission (10% vs 40.4%) and had higher mortality (67.1% vs 33.7%). Only 20 (28.6%) liver injury cases were adjudicated as probable drug‐induced hepatotoxicity; these patients were significantly more likely to present with an hepatocellular/mixed injury pattern (65% vs 12%), to receive corticosteroids (55% vs 12%) and had lower mortality (45% vs 76%) during follow‐up.ConclusionsOncology patients treated with pembrolizumab who develop liver injury experience poorer outcomes during follow‐up. The low incidence of confirmed drug hepatotoxicity highlights the need for thorough medical evaluation before initiating corticosteroids to optimise patient care.
Review article: biological mechanisms for symptom causation by individual FODMAP subgroups ‐ the case for a more personalised approach to dietary restriction
Authors: Wang Xiao Jing , Camilleri Michael , Vanner Stephen , Tuck Caroline 
Published: July 2019

SummaryBackgroundDue to the paucity of targeted therapy for irritable bowel syndrome (IBS), many patients turn to dietary modifications for symptom management. The combination of five subgroups of poorly absorbed and rapidly fermented carbohydrates—fructans, galacto‐oligosaccharides, lactose, excess fructose and polyols—are thought to trigger gastrointestinal symptoms and are referred to collectively as “FODMAPs”.AimsTo examine the biological plausibility and mechanisms by which foods high in specific FODMAP subgroups cause symptoms, and to use this information to explore the possibility of targeting select dietary components to allow for a more personalised approach to dietary adjustmentMethodsRecent literature was analysed via search databases including Medline, PubMed and Scopus.ResultsLactose, fructans and galacto‐oligosaccharides have strong biologic plausibility for symptom generation due to lack of hydrolases resulting in distention from osmosis and rapid fermentation. However, excess fructose and polyols may only cause symptoms in specific individuals when consumed in high doses, but this remains to be established. There is evidence to suggest that certain patient characteristics such as ethnicity may predict response to lactose, but differentiation of other subgroups is difficult prior to dietary manipulation.ConclusionsWhile some clear mechanisms of action for symptom generation have been established, further research is needed to understand which patients will respond to specific FODMAP subgroup restriction. We suggest that clinicians consider in some patients a tailored, personalised “bottom‐up” approach to the low‐FODMAP diet, such as dietary restriction relevant to the patients’ ethnicity, symptom profile and usual dietary intake.
Pathological characteristics of thyroid glands from Japanese Black Cattle living in the restricted area of the Fukushima Daiichi Nuclear Power Plant accident
Authors: Sasaki Jun , Uehara Megumi , Sato Itaru , Satoh Hiroshi , Deguchi Yoshitaka , Chida Hiroyuki , Natsuhori Masahiro , Murata Takahisa , Ochiai Kenji , Otani Kumiko , Okada Keiji , Ito Nobuhiko 
Published: July 2019

AbstractTo study the effect of ionizing radiation on thyroid glands, 66 Japanese Black cattle residing in the restricted area of the Fukushima Daiichi Nuclear Power Plant in 2013–2017 were pathologically examined. There were no clinical symptoms of thyroid disease in these cattle. Three cases of goiter and seven of atrophy were found in two among the four farms examined. Cases of goiter exhibited normal morphological structure without mass or nodule formation in thyroid glands. Cellular atypia or capsular invasion of the follicular epithelium was absent. The estimated integrated dose of external radiation in goiter cases ranged from maximum 797 mSv to minimum 24 mSv. All lobules in the seven atrophic thyroid glands were affected, but pathological findings, such as inflammatory cell infiltration or stromal fibrosis, were not observed. The estimated integrated dose of external radiation in atrophic thyroids ranged from maximum 589 mSv to minimum 8 mSv. Immunohistochemical analysis of anti‐nitroguanosine and the TUNEL method in goiter and atrophic thyroid glands did not reveal any positive findings. The present study indicates that there was no significant relationship between a radiation effect and pathological findings in any thyroid glands.
DVM students report higher psychological distress than the Australian public, medical students, junior medical officers and practicing veterinarians
Authors: Yang HH , Ward MP , Fawcett A 
Published: July 2019

AimTo measure the stress levels of Doctor of Veterinary Medicine (DVM) students at the University of Sydney using the Kessler Psychological Distress Scale (K10) questionnaire.MethodsDVM students in years 1 to 4 were surveyed in semester 2 of 2018. The voluntary online survey consisted of 6 demographic questions and the K10 scale, a standardised measure of stress commonly used in Australia by medical practitioners for evaluation and referral to mental health professionals. Academic year cohorts were compared to identify differences in stress levels. Cohorts were compared to published K10 scores from various populations including the Australian public, medical students, practicing veterinarians, and Junior Medical Officers (JMOs).ResultsThe response rate was 54.4% (n = 237). DVM students experienced a higher level of psychological distress (mean 24, median 23, range 10‐50) than the Australian population (mean 14.5, median 13, range 10‐50), medical students (mean 18.4, median 16, range 10‐50), practicing veterinarians (mean 16.7, median 15.5, range 10‐30), and JMOs (mean 18.1, median 16, range 10‐50). Female students (median 23) had a significantly higher level of psychological distress compared to male students (median 18) (p = 0.0005). International students (median 23) had a higher level of psychological stress than domestic students (median 22) (p = 0.0488). Different year cohorts, age range, work hours, and exercise were not associated with difference in stress levels.ConclusionBased on higher levels of stress in DVM students than that of the general population, practicing veterinarians, JMOs and medical students, there is an urgent need for evidence‐based interventions to target stress in DVM students.
The natural history of untreated muscle‐invasive bladder cancer
Authors: Martini Alberto , Sfakianos John P. , Renström‐Koskela Lotta , Mortezavi Ashkan , Falagario Ugo G. , Egevad Lars , Hosseini Abolfazal , Mehrazin Reza , Galsky Matthew D. , Steineck Gunnar , Wiklund N. Peter 
Published: July 2019

ObjectiveTo describe the natural history of untreated muscle‐invasive bladder cancer (MIBC) and compare the oncological outcomes of treated and untreated patients.Patients and MethodsWe utilised a database encompassing all patients with newly diagnosed bladder cancer in Stockholm, Sweden between 1995 and 1996. The median follow‐up for survivors was 14.4 years. Overall, 538 patients were diagnosed with bladder cancer of whom 126 had clinically localised MIBC. Patients were divided into two groups: those who received radical cystectomy or radiation therapy, and those who did not receive any form of treatment. Multivariable Cox or competing‐risks regressions were adopted to predict metastasis, overall survival (OS), and cancer‐specific mortality (CSM), when appropriate. Analyses were adjusted for age at diagnosis, sex, tumour stage, clinical N stage, and treatment.ResultsIn all, 64 (51%) patients did not receive any definitive local treatment. In the untreated group, the median (interquartile range) age at diagnosis was 79 (63–83) vs 69 (63–74) years in the treated group (P < 0.001). Overall, 109 patients died during follow‐up. At 6 months after diagnosis, 38% of the untreated patients had developed metastatic disease and 41% had CSM. The 5‐year OS rate for untreated and treated patients was 5% (95% confidence interval [CI] 1, 12%) vs 48% (95% CI 36, 60%), respectively. Patients not receiving any treatment had a 5‐year cumulative incidence of CSM of 86% (95% CI 75, 94%) vs 48% (95% CI 36, 60%) for treated patients. Untreated patients had a higher risk of progression to metastatic disease (hazard ratio [HR] 2.40, 95% CI 1.28, 4.51; P = 0.006), death from any cause (HR 2.63, 95% CI 1.65, 4.19; P < 0.001) and CSM (subdistribution HR 2.02, 95% CI 1.24, 3.30; P = 0.004).ConclusionsUntreated patients with MIBC are at very high risk of near‐term CSM. These findings may help balance the risks vs benefits of integrating curative intent therapy particularly in older patients with MIBC.
A Survey on Visual Traffic Simulation: Models, Evaluations, and Applications in Autonomous Driving
Authors: Chao Qianwen , Bi Huikun , Li Weizi , Mao Tianlu , Wang Zhaoqi , Lin Ming C. , Deng Zhigang 
Published: July 2019

AbstractVirtualized traffic via various simulation models and real‐world traffic data are promising approaches to reconstruct detailed traffic flows. A variety of applications can benefit from the virtual traffic, including, but not limited to, video games, virtual reality, traffic engineering and autonomous driving. In this survey, we provide a comprehensive review on the state‐of‐the‐art techniques for traffic simulation and animation. We start with a discussion on three classes of traffic simulation models applied at different levels of detail. Then, we introduce various data‐driven animation techniques, including existing data collection methods, and the validation and evaluation of simulated traffic flows. Next, we discuss how traffic simulations can benefit the training and testing of autonomous vehicles. Finally, we discuss the current states of traffic simulation and animation and suggest future research directions.
Application of multiple‐population viability analysis to evaluate species recovery alternatives
Authors: Neville Helen M. , Leasure Douglas R. , Dauwalter Daniel C. , Dunham Jason B. , Bjork Robin , Fesenmyer Kurt A. , Chelgren Nathan D. , Peacock Mary M. , Luce Charles H. , Isaak Daniel J. , Carranza Lee Ann , Sjoberg Jon , Wenger Seth J. 
Published: July 2019

AbstractPopulation viability analysis (PVA) is a powerful conservation tool, but it remains impractical for many species, particularly species with multiple, broadly distributed populations for which collecting suitable data can be challenging. A recently developed method of multiple‐population viability analysis (MPVA), however, addresses many limitations of traditional PVA. We built on previous development of MPVA for Lahontan cutthroat trout (LCT) (Oncorhynchus clarkii henshawi), a species listed under the U.S. Endangered Species Act, that is distributed broadly across habitat fragments in the Great Basin (U.S.A.). We simulated potential management scenarios and assessed their effects on population sizes and extinction risks in 211 streams, where LCT exist or may be reintroduced. Conservation populations (those managed for recovery) tended to have lower extinction risks than nonconservation populations (mean = 19.8% vs. 52.7%), but not always. Active management or reprioritization may be warranted in some cases. Eliminating non‐native trout had a strong positive effect on overall carrying capacities for LCT populations but often did not translate into lower extinction risks unless simulations also reduced associated stochasticity (to the mean for populations without non‐native trout). Sixty fish or 5–10 fish/km was the minimum reintroduction number and density, respectively, that provided near‐maximum reintroduction success. This modeling framework provided crucial insights and empirical justification for conservation planning and specific adaptive management actions for this threatened species. More broadly, MPVA is applicable to a wide range of species exhibiting geographic rarity and limited availability of abundance data and greatly extends the potential use of empirical PVA for conservation assessment and planning.
Exploring the internal and external wildlife gradients created by conservation fences
Authors: Moseby Katherine E. , McGregor Hugh , Hill Brydie M. , Read John L. 
Published: July 2019

AbstractSpillover effects are an expansion of conservation benefits beyond protected areas through dispersal of species that reside within. They have been well documented in marine but not terrestrial systems. To understand the effects on wildlife created by conservation fences, we explored the internal and external gradients of activity in mammal, reptile, and bird species at a conservation reserve in arid Australia that is fenced to exclude invasive rabbits (Oryctolagus cuniculus), cats (Felis catus), and foxes (Vulpes vulpes). Two methods were used: counts of animal tracks along transects on sand dunes and captures at pitfall‐trapping sites. In both cases, sites were spaced at different distances from the reserve fenceline inside and outside the reserve. We recorded a range of spillover, source‐sink, step, and barrier effects that combined to create a zone within and around the reserve with fence‐induced species‐specific wildlife gradients. Two endemic rodents but none of the 4 mammal species reintroduced to the reserve showed positive spillover effects. Barrier effects, where activity was highest close to the fence, were recorded for the feral cat and native bettong (Bettongia lesueur), species that could not breach the fence. In comparison, some reptiles and native mammal species that could permeate the fence displayed source‐sink effects; that is, their activity levels were reduced close to the fence likely due to constant emigration to the side with lower density. Activity of some reptiles was lowest at sites inside the reserve and gradually increased at outside sites with distance from the fence, a gradient likely related to trophic cascades triggered by predator exclusion. Our result shows that fenced reserves can create overlapping layers of species‐specific gradients related to each species’ ability to permeate the fence and its varying susceptibility to threats. Managers should be aware that these gradients may extend for several kilometers either side of the fence and that not all contained species will increase in abundance. Creating wider conservation benefits may require increased fence permeability and threat reduction outside the fence.
Mechanical circulatory support for cardiac amyloidosis
Authors: Kittleson Michelle M. , Cole Robert M. , Patel Jignesh , Ramzy Danny , Passano Elizabeth , Chang David H. , Geft Dael R. , Czer Lawrence , Vescio Robert , Chung Joshua , Kobashigawa Jon A. , Arabia Francisco , Esmailian Fardad , Moriguchi Jaime D. 
Published: July 2019

AbstractBackgroundCardiac amyloidosis, typically from abnormal deposition of AL or ATTR amyloid protein, can result in heart failure requiring transplantation (HTx). The role of mechanical circulatory support (MCS) is not well‐established. The purpose of this study was to present our experience with MCS in patients with cardiac amyloidosis.MethodsConsecutive patients with cardiac amyloidosis who received MCS at Cedars‐Sinai Medical Center between 2010 and 2018 were reviewed. Clinical characteristics and outcomes were compared to a control group of MCS patients without amyloid matched 2:1 for age and INTERMACS Profile.Results11 amyloid patients underwent durable MCS, two with paracorporeal biventricular assist devices and 9 with total artificial hearts. No patients received isolated left ventricular assist device support. By 1 year, 9 (82%) of patients in the MCS‐Amyloid group had been transplanted and 2 (18%) had died. In the MCS‐No Amyloid group, by 1 year, 8 (36%) of patients had been transplanted, 10 (46%) had died, and 4 (18%) were still living with MCS.ConclusionsOver a 9‐year period, patients with amyloid cardiomyopathy who required MCS at our institution all received durable biventricular MCS. For carefully selected patients, this approach is feasible with acceptable outcomes as bridge to transplantation.
Assessment and prevention of cytomegalovirus infection in allogeneic hematopoietic stem cell transplant and in solid organ transplant: A multidisciplinary consensus conference by the Italian GITMO, SITO, and AMCLI societies
Authors: Girmenia Corrado , Lazzarotto Tiziana , Bonifazi Francesca , Patriarca Francesca , Irrera Giuseppe , Ciceri Fabio , Aversa Franco , Citterio Franco , Cillo Umberto , Cozzi Emanuele , Gringeri Enrico , Baldanti Fausto , Cavallo Rossana , Clerici Pierangelo , Barosi Giovanni , Grossi Paolo 
Published: July 2019

AbstractCytomegalovirus (CMV) remains a major cause of morbidity and mortality in allogeneic hematopoietic stem cell transplantation (allo‐HSCT) and solid organ transplantation (SOT) recipients. In view of the uncertainties on the assessment and prevention of CMV infection in both transplant procedures, three Italian scientific societies for HSCT and SOT and for Clinical Microbiology appointed a panel of experts to compose a framework of recommendations. Recommendations were derived from a comprehensive analysis of the scientific literature and from a multidisciplinary consensus conference process. The lack of adequate clinical trials focused on certain diagnostic procedures, and antiviral intervention forced the panel to use the methods of consensus for shaping some recommendations. Recommendations concerning the two types of transplant were given for the following issues: assessment of pretransplant CMV serostatus, immunological monitoring after transplant, CMV prophylaxis with antivirals, CMV preemptive strategy, and CMV prophylaxis with immunoglobulin infusion and with adoptive immunotherapy. The questions raised by and the recommendations resulting from this consensus conference project may contribute to the improvement of certain crucial aspects of the management of CMV infections in allo‐HSCT and in SOT populations.
Validity of endoscopic features for the diagnosis ofHelicobacter pyloriinfection status based on the Kyoto classification of gastritis
Authors: Yoshii Shinji , Mabe Katsuhiro , Watano Keiko , Ohno Masayoshi , Matsumoto Mio , Ono Shoko , Kudo Takahiko , Nojima Masanori , Kato Mototsugu , Sakamoto Naoya 
Published: July 2019

ObjectivesEvaluation ofHelicobacter pyloriinfection status (non‐infection, past infection, current infection) has become important. This study aimed to determine the usefulness of the Kyoto classification of gastritis for diagnosingH. pyloriinfection status by endoscopy.MethodsIn this prospective study, 498 subjects were recruited. Seven well‐experienced endoscopists blinded to the history of eradication therapy performed the examinations. Endoscopic findings were assessed according to the Kyoto classification of gastritis: diffuse redness, regular arrangement of collecting venules (RAC), fundic gland polyp (FGP), atrophy, xanthoma, hyperplastic polyp, map‐like redness, intestinal metaplasia, nodularity, mucosal swelling, white and flat elevated lesion, sticky mucus, depressive erosion, raised erosion, red streak, and enlarged folds. We established prediction models according to a machine learning procedure and compared them with general assessment by endoscopists using the Kyoto classification of gastritis.ResultsSignificantly higher diagnostic odds were obtained forRAC(32.2),FGP(7.7), and red streak (4.7) in subjects with non‐infection, map‐like redness (12.9) in subjects with past infection, and diffuse redness (26.8), mucosal swelling (13.3), sticky mucus (10.2) and enlarged fold (8.6) in subjects with current infection. The overall diagnostic accuracy rate was 82.9% with the Kyoto classification of gastritis. The diagnostic accuracy of the prediction model was 88.6% for the model withoutH. pylorieradication history and 93.4% for the model with eradication history.ConclusionsThe Kyoto classification of gastritis is useful for diagnosingH. pyloriinfection status based on endoscopic findings. Our prediction model is helpful for novice endoscopists. (UMIN000016674).
Drosophila carboxypeptidase D (SILVER) is a key enzyme in neuropeptide processing required to maintain locomotor activity levels and survival rate
Authors: Pauls Dennis , Hamarat Yasin , Trufasu Luisa , Schendzielorz Tim M. , Gramlich Gertrud , Kahnt Jörg , Vanselow Jens T. , Schlosser Andreas , Wegener Christian 
Published: July 2019

AbstractNeuropeptides are processed from larger preproproteins by a dedicated set of enzymes. The molecular and biochemical mechanisms underlying preproprotein processing and the functional importance of processing enzymes are well‐characterised in mammals, but little studied outside this group. In contrast to mammals, Drosophila melanogaster lacks a gene for carboxypeptidase E (CPE), a key enzyme for mammalian peptide processing. By combining peptidomics and neurogenetics, we addressed the role of carboxypeptidase D (dCPD) in global neuropeptide processing and selected peptide‐regulated behaviours in Drosophila. We found that a deficiency in dCPD results in C‐terminally extended peptides across the peptidome, suggesting that dCPD took over CPE function in the fruit fly. dCPD is widely expressed throughout the nervous system, including peptidergic neurons in the mushroom body and neuroendocrine cells expressing adipokinetic hormone. Conditional hypomorphic mutation in the dCPD‐encoding gene silver in the larva causes lethality, and leads to deficits in starvation‐induced hyperactivity and appetitive gustatory preference, as well as to reduced viability and activity levels in adults. A phylogenomic analysis suggests that loss of CPE is not common to insects, but only occurred in Hymenoptera and Diptera. Our results show that dCPD is a key enzyme for neuropeptide processing and peptide‐regulated behaviour in Drosophila. dCPD thus appears as a suitable target to genetically shut down total neuropeptide production in peptidergic neurons. The persistent occurrence of CPD in insect genomes may point to important further CPD functions beyond neuropeptide processing which cannot be fulfilled by CPE.