bluuebunny/crossref_metadata_2025_split huggingface dataset:
The role of innate immune responses and neuroinflammation in amyloid accumulation and progression of Alzheimer's disease
Authors: Webers Alessandra , Heneka Michael T , Gleeson Paul A 
Published: October 2019

AbstractAlzheimer's disease (AD) is characterized by amyloid beta (Aβ) accumulation, tau pathology and neuroinflammation. Recently, there has been considerable interest in the role of neuroinflammation in directly contributing to the progression of AD. Studies in mice and humans have identified a role for microglial cells, the resident innate immune cells of the central nervous system, in AD. Activated microglia are a key hallmark of the disease and the secretion of proinflammatory cytokines by microglia may result in a positive feedback loop between neurons and microglia, resulting in ongoing low‐grade inflammation. Traditionally, the pathways of Aβ production and neuroinflammation have been considered independently; however, recent studies suggest that these processes may converge to promote the pathology associated with AD. Here we review the importance of inflammation and microglia in AD development and effects of inflammatory responses on cellular pathways of neurons, including Aβ generation.
Multiobjective pseudo‐variable neighborhood descent for a bicriteria parallel machine scheduling problem with setup time
Authors: Queiroz Thiago Alves de , Mundim Leandro Resende 
Published: October 2019

AbstractA multiobjective variable neighborhood descent (VND) based heuristic is developed to solve a bicriteria parallel machine scheduling problem. The problem considers two objectives, one related to the makespan and the other to the flow time, where the setup time depends on the sequence, and the machines are identical. The heuristic has a set of neighborhood structures based on swap, remove, and insertion moves. We propose changing the local search inside the VND to a sequential search through the neighborhoods to obtain nondominated points for the Pareto‐front quickly. In the numerical tests, we consider a single‐objective version of the heuristic, comparing the results on 510 benchmark instances to show that it is quite effective. Moreover, new instances are generated in accordance with the literature for the bicriteria problem, showing the ability of the proposed heuristic to return an efficient set of nondominate solutions compared with the well‐known nondominated sorting genetic algorithm II.
Characterization and modulation of microglial phenotypes in an animal model of severe sepsis
Authors: Michels Monique , Abatti Mariane Rocha , Ávila Pricila , Vieira Andriele , Borges Heloisa , Carvalho Junior Celso , Wendhausen Diogo , Gasparotto Juciano , Tiefensee Ribeiro Camila , Moreira José Claudio Fonseca , Gelain Daniel Pens , Dal‐Pizzol Felipe 
Published: October 2019

AbstractWe aim to characterize the kinetics of early and late microglial phenotypes after systemic inflammation in an animal model of severe sepsis and the effects of minocycline on these phenotypes. Rats were subjected to CLP, and some animals were treated with minocycline (10 ug/kg) by i.c.v. administration. Animals were killed 24 hours, 5, 10 and 30 days after sepsis induction, and serum and hippocampus were collected for subsequent analyses. Real‐time PCR was performed for M1 and M2 markers. TNF‐α, IL‐1β, IL‐6, IL‐10, CCL‐22 and nitrite/nitrate levels were measured. Immunofluorescence for IBA‐1, CD11b and arginase was also performed. We demonstrated that early after sepsis, there was a preponderant up‐regulation of M1 markers, and this was not switched to M2 phenotype markers later on. We found that up‐regulation of both M1 and M2 markers co‐existed up to 30 days after sepsis induction. In addition, minocycline induced a down‐regulation, predominantly, of M1 markers. Our results suggest early activation of M1 microglia that is followed by an overlap of both M1 and M2 phenotypes and that the beneficial effects of minocycline on sepsis‐associated brain dysfunction may be related to its effects predominantly on the M1 phenotype.
Circular RNA USP1 regulates the permeability of blood‐tumour barrier via miR‐194‐5p/FLI1 axis
Authors: Gao Yang , Wu Peiqi , Ma Yawen , Xue Yixue , Liu Yunhui , Zheng Jian , Liu Xiaobai , He Qianru , Ma Jun , Liu Libo , Wang Ping 
Published: October 2019

AbstractRecent studies indicate circular RNAs are related to dysregulation of vascular endothelial cell function, yet the underlying mechanisms have remained elusive. Here, we characterized the functional role of circular RNA USP1 (circ‐USP1) in the regulation of the blood‐tumour barrier (BTB) permeability and the potential mechanisms. In the current study, the circ‐USP1 expressing level was up‐regulated in glioma cerebral microvascular endothelial cells (GECs) of the BTB model in vitro. Knockdown of circ‐USP1 disrupted the barrier integrity, increased its permeability as well as reduced tight junction‐related protein claudin‐5, occludin and ZO‐1 expressions in GECs. Bioinformatic prediction and luciferase assay indicated that circ‐USP1 bound to miR‐194‐5p and suppressed its activity. MiR‐194‐5p contributed to circ‐USP1 knockdown‐induced increase of BTB permeability via targeting and down‐regulating transcription factor FLI1. Furthermore, FLI1 regulated the expressions of claudin‐5, occludin and ZO‐1 in GECs through binding to their promoter regions. Single or combined treatment of circ‐USP1 and miR‐194‐5p effectively promoted anti‐tumour drug doxorubicin across BTB to induce apoptosis of glioma cells. Overall, this present study identified the crucial regulation of circ‐USP1 on BTB permeability via miR‐194‐5p/FLI1 axis‐mediated regulation of tight junction proteins, which might facilitate the development of therapeutics against human gliomas.
Cost‐effectiveness of psychological interventions for children and young people with post‐traumatic stress disorder
Authors: Mavranezouli Ifigeneia , Megnin‐Viggars Odette , Trickey David , Meiser‐Stedman Richard , Daly Caitlin , Dias Sofia , Stockton Sarah , Pilling Stephen 
Published: October 2019

BackgroundPTSD in youth may lead to long‐lasting psychological implications, educational difficulties and increased healthcare costs. Psychological interventions have been shown to be effective in its management. The objective of this study was to assess the cost‐effectiveness of a range of psychological interventions for children and young people with PTSD.MethodsA decision‐analytic model was constructed to compare costs and quality‐adjusted life years (QALYs) of 10 psychological interventions and no treatment for children and young people with PTSD, from the perspective of the National Health Service and personal social services in England. Effectiveness data were derived from a systematic review and network meta‐analysis. Other model input parameters were based on published sources, supplemented by expert opinion.ResultsCognitive therapy for PTSD, a form of individual trauma‐focused cognitive behavioural therapy (TF‐CBT), appeared to be the most cost‐effective intervention for children and young people with PTSD (with a probability of .78 amongst the 11 evaluated options at a cost‐effectiveness threshold of £20,000/QALY), followed by narrative exposure (another form of individual TF‐CBT), play therapy, and other forms of individual TF‐CBT. After excluding cognitive therapy from the analysis, narrative exposure appeared to be the most cost‐effective option with a .40 probability of being cost‐effective amongst the remaining 10 options. EMDR, parent training and group TF‐CBT occupied middle cost‐effectiveness rankings. Family therapy and supportive counselling were less cost‐effective than other active interventions. There was limited evidence for some interventions, in particular cognitive therapy for PTSD and parent training.ConclusionsIndividual forms of TF‐CBT and, to a lesser degree, play therapy appear to be cost‐effective in the treatment of children and young people with PTSD. Family therapy and supportive counselling are unlikely to be cost‐effective relative to other interventions. There is a need for well‐conducted studies that examine the long‐term clinical and cost‐effectiveness of a range of psychological treatments for children and young people with PTSD.
What do highly narcissistic people think and feel about (their) intelligence?
Authors: Zajenkowski Marcin , Czarna Anna Z. , Szymaniak Kinga , Dufner Michael 
Published: October 2019

AbstractObjectiveThe current research comprehensively examined how grandiose and vulnerable narcissism are linked to intelligence and intelligence‐related beliefs and emotions.MethodIn four studies (total N = 1,141), we tested the associations between both forms of narcissism, subjectively and objectively assessed intelligence, basic personality traits, test‐related stress, beliefs about intelligence, and well‐being.ResultsBoth forms of narcissism (grandiose and vulnerable) were unrelated to objective intelligence. Grandiose narcissism was associated with high self‐perceived intelligence (Studies 1–3) and explained more variance in self‐perceived intelligence than objective intelligence and the Big Five personality traits. It was correlated with reduced distress in the context of IQ testing and low engagement in cognitive performance (Study 2). Individuals with high grandiose narcissism based their well‐being (Study 3) partly on intelligence and considered intelligence important for success in different life domains, especially for social relations (Study 4). Vulnerable narcissism was unrelated to self‐perceived intelligence (Studies 1–3) and went along with increased distress in the context of IQ testing (Study 2).ConclusionsThe results indicate that the topic of intelligence is of key importance for people with high grandiose narcissism psychological functioning and it also has some relevance for individuals with high vulnerable narcissism.
Use of clinician‐performed ultrasound in the assessment of safe umbilical venous catheter tip placement
Authors: Seigel Amber , Evans Nick , Lutz Tracey 
Published: October 2019

AimSafe tip placement of umbilical venous catheters (UVCs) in sick neonates is critical in minimising risk. We aimed to demonstrate the utility of clinician‐performed ultrasound (CPU) in identifying UVCs that are placed within small intrahepatic portal vessels or within the heart despite the appearance of being well placed on X‐ray.MethodsThis was a retrospective observational study of preterm and term neonates who had a UVC placed and the position assessed by X‐ray and/or CPU according to the Royal Prince Alfred Hospital level 3 neonatal intensive care unit (NICU) guideline. Cases were identified by exporting the records of all admissions between 1 April 2015 and 30 June 2016 from the NICU's data collection database. Paper‐based medical records, NICU's data collection database records and the ultrasound reporting system were reviewed to determine X‐ray and CPU findings.ResultsA total of 157 neonates had 169 UVCs placed. CPU was performed in 77% (111). In 15 cases (14%), UVC placement on X‐ray appeared appropriate based on estimated vertebral level; however, CPU demonstrated the line to be in an unsafe position (small intrahepatic portal vessel (3); right atrium (9); left atrium (3)).ConclusionsAssessment of safe UVC placement by estimations according to vertebral level on X‐ray alone is inadequate. CPU offers confident localisation of the UVC tip and enables corrective manipulation of intracardiac or intrahepatic UVCs in real time. We recommend CPU as an adjunct to X‐ray to ensure safe UVC placement.
Acid induced gelation behavior of skim milk concentrated by membrane filtration
Authors: Li Ying , Corredig Milena 
Published: October 2019

AbstractThis work reports a detailed study of the effect of ultrafiltration (UF) and diafiltration (DF) on the acid‐induced gelation behavior of fresh milk retentates (2× and 4×). Concentrates were heated at 80°C for 15 min, and compared to unheated samples. The use of extensive DF caused a significantly greater amount of protein (both caseins and whey proteins) in the supernatant fraction, compared to UF retentates at the same concentration, both in unheated and heated samples. DF retentates showed higher pH of gelation, compared to the corresponding UF retentates. The development of tan δ is reported for the first time as a function of colloidal calcium release, and the protein gelation behavior discussed in light differences in composition of the soluble fraction. The results demonstrate how processing history can affect compositional changes and the gelation behavior of fresh milk retentates. Membrane filtration is a widespread unit operation in the dairy industry, employed either to prepare fresh concentrates for further processing, or ingredients with specific functional properties. This work describes in detail the effect of processing history during membrane filtration on the rheological properties of acid induced gels and will help in optimizing formulations and prepare the right ingredients for the right application. It will also be possible to determine new ways to define processing quality of the milk protein concentrates, as it relates to their ability to form texture in fermented dairy products.
Long‐term morbidity and mortality in a Canadian post‐transfusion hepatitis C cohort: Over 15 years of follow‐up
Authors: Sahakyan Yeva , Wong William WL , Yi Qilong , Thein Hla‐Hla , Tomlinson George A , Krahn Murray D 
Published: October 2019

AbstractThe Federal Government of Canada established a $1.1 billion compensation programme in 1999 to support individuals who acquired hepatitis C virus (HCV) through blood products between January 1986 and July 1990. We aimed to describe the morbidity and mortality of this unique post‐transfusion cohort (n = 4550) followed for over 15 years from 2000 to 2016. The age‐standardized mortality rates were compared with that of the Canadian general population and HCV cohorts from other countries. We evaluated all‐cause mortality using Kaplan‐Meier survival curves and HCV‐related and unrelated mortality using competing risk models. The age‐standardized all‐cause and HCV‐related mortality rates per 10 000 person‐years were 127 (95% CI: 117‐138) and 76 (95% CI: 69‐85) for males, and 77 (95% CI: 69‐87) and 43 (95% CI: 37‐51) for females, respectively. The risk of death of the post‐transfusion cohort was almost twice as high as the Canadian general population (rate ratio = 1.8; 95% CI: 1.7‐1.9). All‐cause, HCV‐related and HCV‐unrelated mortality were 20%, 12% and 8%, respectively at 15 years of follow‐up. By comparison, HCV‐related mortality rates per 10 000 person‐years for population‐based HCV cohorts varied from 18 and 11 in Australia to 65 and 43 in Scotland for males and females, respectively. We reported long‐term follow‐up data for the largest post‐transfusion cohort in the literature. The all‐cause mortality rates were markedly higher than that of the Canadian general population. We also showed that HCV‐related mortality were greater compared to other HCV cohorts. This suggests that continued efforts to identify and treat post‐transfusion HCV are warranted.
Direct‐acting antiviral interactions with opioids, alcohol or illicit drugs of abuse in HCV‐infected patients
Authors: Ing Lorenzini Kuntheavy , Girardin François 
Published: October 2019

AbstractThe hepatitis C virus (HCV) prevalence is extremely high in patients who consume and inject illicit drugs. Concerns about poor adherence and fear of interaction with drugs of abuse could constitute further disincentive for treatment initiation in these patients. We discussed the pharmacokinetics (PKs) and pharmacodynamics (PD) of currently prescribed direct antiviral agents (NSA5 inhibitors: daclatasvir, elbasvir, ledipasvir, pibrentasvir, velpatasvir; NS5B inhibitor: sofosbuvir; NS3/4A protease inhibitors: glecaprevir, grazoprevir, voxilaprevir) and most common substances of abuse (opioids: buprenorphine, fentanyl, heroin, methadone, morphine, oxycodone; stimulants: amphetamines, cathinones, cocaine; cannabinoids; ethanol). Overall, most direct‐acting antivirals (DAAs) are substrates and inhibitors of the transmembrane transporter P‐glycoprotein (P‐gp), and several of them are metabolized by cytochrome P450 enzymes. Clinically relevant interactions are associated with P‐gp and CYP3A modulators. Most substances of abuse are eliminated by Phase I and Phase II metabolizing enzymes, but none of them are either major inhibitors or inducers. PK studies did not show any relevant interactions between DAA and methadone or buprenorphine. Based on pharmacological considerations, neither efficacy loss nor adverse drug event associated with detrimental interaction are expected with opioids, stimulants, cannabinoids and ethanol. In summary, our literature review shows that the interaction potential of DAA with most opioids and illicit drugs is limited and should not be a hurdle to the initiate DAA.
Evolution and paleobiogeography of mangroves
Authors: Srivastava Jyoti , Prasad Vandana 
Published: October 2019

AbstractWe reviewed the geological record of mangroves based on fossil pollen, fruits, and wood evidence ofNypa,Avicennia,Sonneratia, Rhizophoraceae, and mangrove associates to trace the origin, distribution, extinction, and range contraction of paleo‐mangroves during the Late Cretaceous–Miocene time. Our study region covers paleocoastal areas of Indo‐West Pacific (IWP) and Atlantic East Pacific (AEP) region. First, we compiled the mangrove fossil records from the Late Cretaceous till Miocene and identified the migration pattern forNypa, Avicennia,Sonneratia, Rhizophoraceae members, and mangrove associates such asAcrostichum, Wetherellia, Pelliciera, Aegiceras, Heritiera, Excoecaria,andBarringtonia. Second, we interpreted the paleoclimate shifts which caused the dispersal/extinction of this specialized ecosystem. Lastly, we proposed the future consequences of mangrove diversity for restoration and conservation strategies. First mangroves appeared during the Late Cretaceous, 100–65 Ma, since then their evolution is closely related to sea‐level changes in geological times. The oldest geological record ofNypapalm which prefers broad ecological tolerance is a good example for pantropical distribution of mangroves. High sea‐level and humid climate offered sufficient coastal regions and climate for the development of 12 genera of mangroves in nine families and subsequent proliferation into newer areas during early to middle Eocene (~50–40 Ma). The Eocene/Oligocene boundary crisis heralds the beginning of a biogeographical split between the present‐day eastern and western provinces of mangroves with records ofSonneratia,Rhizophora, Pelliciera, Barringtonia,andAcrostichum. However, during Oligocene and Middle Miocene mangroves occupied the present geographical position with addition ofNypa,Avicennia,andExcoecariaspecies. Re‐evaluation of Cenozoic records suggests that the climatic conditions of Late Paleocene, end of Eocene, and middle Pliocene were the driving force that led to the evolution and expansion of mangrove flora. During the Neogene, latitudinal contraction, extinction, and migration of mangroves led to the present bipartite distribution. The Himalayan uplift and establishment of Asian summer monsoon toward Late Neogene further affected the coastal dynamics which tailored the mangrove distribution of the Indian subcontinent. Loss of ecological habitats and local extinction forming disjunct distribution of mangroves during the Quaternary have also affected its overall biogeography.
Epidemiology of emergency department acute kidney injury
Authors: Foxwell David A. , Pradhan Sara , Zouwail Soha , Rainer Timothy H. , Phillips Aled O. 
Published: October 2019

AbstractAimThe epidemiology of acute kidney injury (AKI) diagnosed in the emergency department (ED) is poorly described. This study describes the incidence, demographics and outcomes of patients diagnosed with AKI in the ED (ED‐AKI).MethodsA prospective cohort study was completed in a University Teaching Hospital, (UK) between April and August 2016. In total, 20  421 adult patients attended the ED and had a serum creatinine measurement. The incident ED‐AKI patient episodes were compared with a randomly selected cohort of non‐AKI ED patients.ResultsA total of 572 patients had confirmed eAlert ED‐AKI (548 incident cases), incidence 2.8% (of all ED attendances). ED‐AKI was associated with a 24.4% in‐patient mortality (non‐AKI 3.2%, P < .001) of which 22.3% of deaths occurred within 24 hours and 58% within 7 days. Progression of the admission AKI stage to a higher AKI stage was associated with a 38.8% mortality compared with a 21.4% mortality in those who did not progress (P < .001). In multivariate analysis, ED‐AKI was an independent risk for mortality (hazard ratio, 6.293; 95% confidence interval, 1.887‐20.790, P = .003). For those discharged from hospital, 20.4% of ED‐AKI patients re‐attend for acute assessment within 30‐days post‐discharge (non‐AKI 7.6%, P < .001). At 90‐days post‐discharge, 10.0% of ED‐AKI patients died (non‐AKI 1.4%, P < .001). Twelve months post‐discharge 17.8% of ED‐AKI patients developed CKD progression or de‐novo CKD (non‐AKI 6.0%).ConclusionThe ED‐AKI is an independent predictor of death. Mortality is predominantly in the early stages of hospital admission, but for those who survive to discharge have significant long‐term morbidity and mortality.
Adult stem cells and regenerative medicine—a symposium report
Authors: Cable Jennifer , Fuchs Elaine , Weissman Irving , Jasper Heinrich , Glass David , Rando Thomas A. , Blau Helen , Debnath Shawon , Oliva Anthony , Park Sangbum , Passegué Emmanuelle , Kim Carla , Krasnow Mark A. 
Published: October 2019

AbstractAdult stem cells are rare, undifferentiated cells found in all tissues of the body. Although normally kept in a quiescent, nondividing state, these cells can proliferate and differentiate to replace naturally dying cells within their tissue and to repair its wounds in response to injury. Due to their proliferative nature and ability to regenerate tissue, adult stem cells have the potential to treat a variety of degenerative diseases as well as aging. In addition, since stem cells are often thought to be the source of malignant tumors, understanding the mechanisms that keep their proliferative abilities in check can pave the way for new cancer therapies. While adult stem cells have had limited practical and clinical applications to date, several clinical trials of stem cell–based therapies are underway. This report details recent research presented at the New York Academy of Sciences on March 14, 2019 on understanding the factors that regulate stem cell activity and differentiation, with the hope of translating these findings into the clinic.
Osteoradionecrosis beyond the jaws: a mini case series and review of the literature
Authors: Wali R. , King R. , Patel V. 
Published: October 2019

AbstractOsteoradionecrosis (ORN) of the mandible is a well‐known complication of head and neck radiotherapy (RT). In contrast, osteonecrosis of surrounding non‐target structures in the craniofacial region is less commonly reported. Various bones within the head and neck are susceptible to ORN and this may present years after initial radiation exposure especially with improving survival rates. We report three cases of ORN involving the hyoid bone and temporal bone, and review the literature regarding numerous bones within the head and neck skeleton that have been affected by ORN.