bluuebunny/crossref_metadata_2025_split huggingface dataset:
The center of olfactory bulb‐seeded α‐synucleinopathy is the limbic system and the ensuing pathology is higher in male than in female mice
Authors: Mason Daniel M. , Wang Yaqin , Bhatia Tarun N. , Miner Kristin M. , Trbojevic Sara A. , Stolz John F. , Luk Kelvin C. , Leak Rehana K. 
Published: March 2019

AbstractAt early disease stages, Lewy body disorders are characterized by limbic vs. brainstem α‐synucleinopathy, but most preclinical studies have focused solely on the nigrostriatal pathway. Furthermore, male gender and advanced age are two major risk factors for this family of conditions, but their influence on the topographical extents of α‐synucleinopathy and the degree of cell loss are uncertain. To fill these gaps, we infused α‐synuclein fibrils in the olfactory bulb/anterior olfactory nucleus complex—one of the earliest and most frequently affected brain regions in Lewy body disorders—in 3‐month‐old female and male mice and in 11‐month‐old male mice. After 6 months, we observed that α‐synucleinopathy did not expand significantly beyond the limbic connectome in the 9‐month‐old male and female mice or in the 17‐month‐old male mice. However, the 9‐month‐old male mice had developed greater α‐synucleinopathy, smell impairment and cell loss than age‐matched females. By 10.5 months post‐infusion, fibril treatment hastened mortality in the 21.5‐month‐old males, but the inclusions remained centered in the limbic system in the survivors. Although fibril infusions reduced the number of cells expressing tyrosine hydroxylase in the substantia nigra of young males at 6 months post‐infusion, this was not attributable to true cell death. Furthermore, mesencephalic α‐synucleinopathy, if present, was centered in mesolimbic circuits (ventral tegmental area/accumbens) rather than within strict boundaries of the nigral pars compacta, which were defined here by tyrosine hydroxylase immunolabel. Nonprimate models cannot be expected to faithfully recapitulate human Lewy body disorders, but our murine model seems reasonably suited to (i) capture some aspects of Stage IIb of Lewy body disorders, which displays a heavier limbic than brainstem component compared to incipient Parkinson’s disease; and (ii) leverage sex differences and the acceleration of mortality following induction of olfactory α‐synucleinopathy.
Use of Delphian lymph node metastasis to predict central and lateral involvement in papillary thyroid carcinoma: A systematic review and meta‐analysis
Authors: Huang Jiapeng , Sun Wei , Zhang Hao , Zhang Ping , Wang Zhihong , Dong Wenwu , He Liang , Zhang Ting 
Published: March 2019

SummaryObjectiveWhether Delphian lymph node (DLN) metastasis is a reliable predictor of widespread lymph node metastasis in papillary thyroid carcinoma (PTC) remains controversial. This meta‐analysis investigated the value of DLN metastasis for predicting central and lateral involvement in PTC.Design and MethodsA literature search using the PubMed, SCIE and the Chinese National Knowledge Infrastructure (CNKI) databases was conducted. Two reviewers independently extracted data and evaluated the studies for inclusion. Fixed‐effects and random‐effects models were used to analyse the data based on their heterogeneity. A sensitivity analysis was performed, and publication bias was assessed using Begg's funnel plot and Egger's linear regression test.ResultsData from 10 studies were analysed. The risk of central lymph node (CLN) metastasis was significantly higher in the DLN‐positive group than in the DLN‐negative group (OR = 9.05, 95% CI: 5.13‐15.99) with moderate heterogeneity (P = 0.022, I2 = 53.5%). The risk of lateral lymph node (LLN) metastasis was significantly higher in the DLN‐positive group than in the negative group (OR = 10.88, 95% CI: 7.60‐15.58), with low heterogeneity (P = 0.603, I2 = 0.0%). Sensitivity analysis indicated that the results were stable and credible, and no publication bias was found.ConclusionsDelphian lymph node metastasis is valuable for predicting central and lateral compartment involvement in patients with PTC. The DLN of PTC patients should be dissected intraoperatively and sent for frozen section consultation. If the result is positive, the CLNs should be thoroughly dissected and the LLNs should be further evaluated.
Hand eczema patients’ knowledge of skin protection following a guided talk—A retrospective study with a follow‐up questionnaire
Authors: Topal Yasemin , Agner Tove , van der Heiden Janique , Ebbehøj Niels E. , Clemmensen Kim K. B. 
Published: March 2019

AbstractBackgroundSeveral studies have assessed the effect of patient education regarding hand eczema (HE) severity and quality of life. Few studies, however, have evaluated patients’ knowledge.ObjectivesTo examine knowledge of skin protection in HE patients following a guided talk, and to identify variables associated with knowledge.MethodsHE patients referred to the outpatient dermatological clinic, Bispebjerg Hospital, between January 2013 and July 2014 were offered a guided talk on HE prevention. HE severity and the Dermatology Life Quality Index (DLQI) score were assessed. A questionnaire comprising 10 questions about skin protection was sent 1 to 2.5 years later.ResultsOne hundred and twenty patients responded to the questionnaire (response 53.5%). The mean percentage of correct answers was 74.7%. Sixty per cent responded correctly to at least eight questions. Male sex, older age and education for >5 years were associated with a low level of knowledge. Education for 3 to 4 years (P = 0.045) was associated with a higher level of knowledge. No significant impact of previous/current atopic dermatitis, HE severity or previous information on skin protection was found with respect to level of knowledge.ConclusionsFemales and patients with education for 3 to 4 years showed the highest level of knowledge, whereas males, older patients and patients with education for >5 years should be brought more into focus in skin protection programmes.
Induction of neutrophil extracellular traps during tissue injury: Involvement of STING and Toll‐like receptor 9 pathways
Authors: Liu Li , Mao Ye , Xu Bocheng , Zhang Xiangxian , Fang Chunju , Ma Yu , Men Ke , Qi Xiaorong , Yi Tao , Wei Yuquan , Wei Xiawei 
Published: March 2019

AbstractObjectivesNeutrophils are thought to release neutrophil extracellular traps (NETs) to form in response to exogenous bacteria, viruses and other pathogens. However, the mechanisms underlying NET formation during sterile inflammation are still unclear. In this study, we would like to identify neutrophil extracellular traps formation during sterile inflammation and tissue injury and associated pathways and its mechanism.Materials and methodsWe identified different injuries such as chemical‐induced and trauma‐induced formation of NETs and investigated mechanism of the formation of NETs in vitro and in vivo during the treatment of mtDNA.ResultsHere, we find the release of mitochondrial DNA (mtDNA) and oxidized mtDNA in acute peripheral tissue trauma models or other chemically induced lung injury, and moreover, endogenous mtDNA and oxidized mtDNA induce the formation of NETs and sterile inflammation. Oxidized mtDNA is a more potent inducer of NETs. Mitochondrial DNA activates neutrophils via cyclic GMP‐AMP synthase (cGAS)‐STING and the Toll‐like receptor 9 (TLR9) pathways and increases the production of neutrophil elastase and extracellular neutrophil‐derived DNA in NETs. Mitochondrial DNA also increases the production of reactive oxygen species (ROS) and expression of the NET‐associated proteins Rac 2 and peptidylarginine deiminase 4 (PAD4).ConclusionsAltogether, these findings highlight that endogenous mitochondrial DNA inducted NETs formation and subsequent sterile inflammation and the mechanism associated with NET formation.
Primary cutaneous diffuse large B‐cell lymphoma, NOS and leg type: Clinical, morphologic and prognostic differences
Authors: Felcht Moritz , Klemke Claus‐Detlev , Nicolay Jan Peter , Weiss Christel , Assaf Chalid , Wobser Marion , Schlaak Max , Hillen Uwe , Moritz Rose , Tantcheva‐Poor Iliana , Nashan Dorothee , Beyer Marc , Dippel Edgar , Müller Cornelia Sigrid Lissi , Sachse Michael Max , Meiss Frank , Géraud Cyrill , Marx Alexander , Goerdt Sergij , Geissinger Eva , Kempf Werner 
Published: March 2019

SummaryBackground and objectivesPrimary cutaneous diffuse large B‐cell lymphoma, NOS (PCLBCL/NOS) is a rare PCLBCL. Only few data are available for this tumor. The aim of this study was to identify clinical and/or immunohistochemical markers (in addition to Bcl‐2) that characterize PCLBCL/NOS, assist in differentiating it from PCLBCL, leg type (PCLBCL/LT) and help to assess the clinical course/prognosis.Patients and methodsBcl‐2– PCLBCL/NOS) cases (n = 14 were compared with Bcl‐2+ PCLBCL/LT cases (n = 29).ResultsPCLBCL/NOS patients were younger, predominantly male and had better survival rates than patients with PCLBCL/LT. Patients with PCLBCL/NOS presented more often with larger plaques limited to one or two contiguous body regions, whereas PCLBCL/LT cases often presented with disseminated lesions. Neoplastic cells had a higher proliferation rate (Ki67) in PCLBCL/LT patients. The tumor microenvironment of PCLBCL/NOS had a more prominent CD3+ infiltrate. Overall survival data for the whole cohort (n = 37) revealed that female gender and Bcl‐2 expression correlated with a worse survival rate. Bcl‐6 expression and centroblastic subtype correlated with better outcomes. None of the other markers studied (e.g. GCB/non‐GCB subtype) correlated with survival rate.ConclusionsPCLBCL/NOS and PCLBCL/LT differ in their clinical behavior and outcomes. Bcl‐2 still seems to be the best marker for discriminating between these two subgroups. Bcl‐2, female gender and Bcl‐6 represent prognostic markers for PCLBCL.
Take Control: A randomized trial evaluating the efficacy and safety of self‐ versus physician‐managed titration of insulin glargine 300 U/mL in patients with uncontrolled type 2 diabetes
Authors: Russell‐Jones David , Dauchy Arnaud , Delgado Elías , Dimitriadis George , Frandsen Hans A. , Popescu Luiza , Schultes Bernd , Strojek Krzysztof , Bonnemaire Mireille , Roborel de Climens Aude , Davies Melanie 
Published: March 2019

AimTo compare the efficacy and safety of self‐ versus physician‐managed titration of insulin glargine 300 U/mL (Gla‐300) in people with inadequately controlled type 2 diabetes.MethodsTake Control (EudraCT number: 2015‐001626‐42) was a 24‐week, multi‐national, open‐label, controlled, two‐arm, parallel‐group study in insulin‐naïve and pre‐treated participants, randomized 1:1 to a self‐ or physician‐managed titration of Gla‐300. The fasting self‐monitored plasma glucose (SMPG) target was 4.4 to 7.2 mmol/L. The primary outcome was non‐inferiority of glycated haemoglobin (HbA1c) change from baseline to week 24. Secondary outcomes included SMPG target achievement without hypoglycaemia, hypoglycaemia incidence, adverse events and participant‐reported outcomes (PROs).ResultsAt week 24, the least squares (LS) mean HbA1c reduction was 0.97% (10.6 mmol/mol) and 0.84% (9.2 mmol/mol) in the self‐ and physician‐managed groups, respectively, with an LS mean difference of −0.13% [95% confidence interval −0.2619 to −0.0004] (–1.4 mmol/mol [–2.863 to –0.004]), demonstrating non‐inferiority (P < 0.0001) and superiority (P = 0.0247) of self‐ versus physician‐managed titration. Significantly more of the self‐ than physician‐managed group achieved SMPG target without hypoglycaemia (67% vs 58%; P = 0.0187). Overall, hypoglycaemia incidence was similar in each group. No safety concerns were reported. In both groups, similar PRO improvements were observed for distress related to diabetes disease burden and for confidence in diabetes self‐management, with even more individuals achieving a clinically relevant reduction in emotional burden and fewer individuals with high emotional burden in the self‐managed group.ConclusionsSelf‐managed titration of Gla‐300 was superior to physician‐managed titration in terms of HbA1c reduction, accompanied by similar total PRO scores, with a clinically relevant reduction in emotional burden, and similar hypoglycaemia frequency.
Cardiovascular safety and lower severe hypoglycaemia of insulin degludec versus insulin glargine U100 in patients with type 2 diabetes aged 65 years or older: Results from DEVOTE (DEVOTE 7)
Authors: Pratley Richard E. , Emerson Scott S. , Franek Edward , Gilbert Matthew P. , Marso Steven P. , McGuire Darren K. , Pieber Thomas R. , Zinman Bernard , Hansen Charlotte T. , Hansen Melissa V. , Mark Thomas , Moses Alan C. , Buse John B. ,   on behalf of the DEVOTE Study Group
Published: March 2019

AimsThe aim of this study was to describe the risks of cardiovascular (CV) events and severe hypoglycaemia with insulin degludec (degludec) vs insulin glargine 100 units/mL (glargine U100) in patients with type 2 diabetes (T2D) aged 65 years or older.Materials and methodsA total of 7637 patients in the DEVOTE trial, a treat‐to‐target, randomized, double‐blind trial evaluating the CV safety of degludec vs glargine U100, were divided into three age groups (50‐64 years, n = 3682; 65‐74 years, n = 3136; ≥75 years, n = 819). Outcomes by overall age group and randomized treatment differences were analysed for major adverse cardiovascular events (MACE), all‐cause mortality, severe hypoglycaemia and serious adverse events (SAEs).ResultsPatients with increasing age had higher risks of CV death, all‐cause mortality and SAEs, and there were non‐significant trends towards higher risks of MACE and severe hypoglycaemia. Treatment effects on the risk of MACE, all‐cause mortality, severe hypoglycaemia and SAEs were consistent across age groups, based on the non‐significant interactions between treatment and age with regard to these outcomes.ConclusionsThere were higher risks of CV death, all‐cause mortality and SAEs, and trends towards higher risks of MACE and severe hypoglycaemia with increasing age after adjusting for baseline differences. The effects across age groups of degludec vs glargine U100 on MACE, all‐cause mortality and severe hypoglycaemia were comparable, suggesting that the risk of MACE, as well as all‐cause mortality, is similar and the risk of severe hypoglycaemia is lower with degludec regardless of age. Evidence is conclusive only until 74 years of age.
The spectrum of neuroimaging findings in febrile infection‐related epilepsy syndrome (FIRES): A literature review
Authors: Culleton Sinead , Talenti Giacomo , Kaliakatsos Marios , Pujar Suresh , D'Arco Felice 
Published: March 2019

SummaryFebrile infection‐related epilepsy syndrome (FIRES) is a rare severe epileptic syndrome occurring in previously healthy children and characterized by refractory status epilepticus (SE) following a febrile illness. Brain imaging findings in affected patients have been reported in few case series and some case reports. This article is a comprehensive review of the magnetic resonance imaging (MRI)characteristics in all reported patients with a diagnosis ofFIRES, describing the findings in the acute and chronic phases of the disease, and discussing possible pathogenesis and radiologic differential diagnoses. Most of the patients had normal brain scans in the acute phase (61%) and about 25% of the patients reported in literature had abnormalities in the temporal lobes. Changes in the basal ganglia and rarely in thalami or brainstem have also been described, as well as diffuse cerebral edema in a minority of patients during the acute phase. The chronic phase of the disease was characterized by atrophic changes and evidence of mesiotemporal sclerosis. An understanding of theseMRIabnormalities is necessary to support the diagnosis ofFIRESand exclude mimics.
Potassium channels in vascular smooth muscle: a pathophysiological and pharmacological perspective
Authors: Dogan Muhammed Fatih , Yildiz Oguzhan , Arslan Seyfullah Oktay , Ulusoy Kemal Gokhan 
Published: March 2019

AbstractPotassium (K+) ion channel activity is an important determinant of vascular tone by regulating cell membrane potential (MP). Activation of K+ channels leads to membrane hyperpolarization and subsequently vasodilatation, while inhibition of the channels causes membrane depolarization and then vasoconstriction. So far five distinct types of K+ channels have been identified in vascular smooth muscle cells (VSMCs): Ca+2‐activated K+ channels (BKCa), voltage‐dependent K+ channels (KV), ATP‐sensitive K+ channels (KATP), inward rectifier K+ channels (Kir), and tandem two‐pore K+ channels (K2P). The activity and expression of vascular K+ channels are changed during major vascular diseases such as hypertension, pulmonary hypertension, hypercholesterolemia, atherosclerosis, and diabetes mellitus. The defective function of K+ channels is commonly associated with impaired vascular responses and is likely to become as a result of changes in K+ channels during vascular diseases. Increased K+ channel function and expression may also help to compensate for increased abnormal vascular tone. There are many pharmacological and genotypic studies which were carried out on the subtypes of K+ channels expressed in variable amounts in different vascular beds. Modulation of K+ channel activity by molecular approaches and selective drug development may be a novel treatment modality for vascular dysfunction in the future. This review presents the basic properties, physiological functions, pathophysiological, and pharmacological roles of the five major classes of K+ channels that have been determined in VSMCs.
Woody vegetation dynamics in the tropical and subtropical Andes from 2001 to 2014: Satellite image interpretation and expert validation
Authors: Aide T. Mitchell , Grau H. Ricardo , Graesser Jordan , Andrade‐Nuñez Maria Jose , Aráoz Ezequiel , Barros Ana P. , Campos‐Cerqueira Marconi , Chacon‐Moreno Eulogio , Cuesta Francisco , Espinoza Raul , Peralvo Manuel , Polk Molly H. , Rueda Ximena , Sanchez Adriana , Young Kenneth R. , Zarbá Lucía , Zimmerer Karl S. 
Published: March 2019

AbstractThe interactions between climate and land‐use change are dictating the distribution of flora and fauna and reshuffling biotic community composition around the world. Tropical mountains are particularly sensitive because they often have a high human population density, a long history of agriculture, range‐restricted species, and high‐beta diversity due to a steep elevation gradient. Here we evaluated the change in distribution of woody vegetation in the tropical Andes of South America for the period 2001–2014. For the analyses we created annual land‐cover/land‐use maps using MODIS satellite data at 250 m pixel resolution, calculated the cover of woody vegetation (trees and shrubs) in 9,274 hexagons of 115.47 km2, and then determined if there was a statistically significant (p < 0.05) 14 year linear trend (positive—forest gain, negative—forest loss) within each hexagon. Of the 1,308 hexagons with significant trends, 36.6% (n = 479) lost forests and 63.4% (n = 829) gained forests. We estimated an overall net gain of ~500,000 ha in woody vegetation. Forest loss dominated the 1,000–1,499 m elevation zone and forest gain dominated above 1,500 m. The most important transitions were forest loss at lower elevations for pastures and croplands, forest gain in abandoned pastures and cropland in mid‐elevation areas, and shrub encroachment into highland grasslands. Expert validation confirmed the observed trends, but some areas of apparent forest gain were associated with new shade coffee, pine, or eucalypt plantations. In addition, after controlling for elevation and country, forest gain was associated with a decline in the rural population. Although we document an overall gain in forest cover, the recent reversal of forest gains in Colombia demonstrates that these coupled natural‐human systems are highly dynamic and there is an urgent need of a regional real‐time land‐use, biodiversity, and ecosystem services monitoring network.
Automated FRET quantification shows distinct subcellular ERK activation kinetics in response to graded EGFR signaling in Drosophila
Authors: Ogura Yosuke , Sami Mustafa M. , Wada Housei , Hayashi Shigeo 
Published: March 2019

AbstractThreshold responses to an activity gradient allow a single signaling pathway to yield multiple outcomes. Extracellular signal‐regulated kinase (ERK) is one such signal, which couples receptor tyrosine kinase signaling with multiple cellular responses in various developmental processes. Recent advances in the development of fluorescent biosensors for live imaging have enabled the signaling activities accompanying embryonic development to be monitored in real time. Here, we used an automated computational program to quantify the signals of a fluorescence resonance energy transfer (FRET) reporter for activated ERK, and we used this system to monitor the spatio‐temporal dynamics of ERK during neuroectoderm patterning in Drosophila embryos. We found that the cytoplasmic and nuclear ERK activity gradients show distinct kinetics in response to epidermal growth factor receptor activation. The ERK activation patterns implied that the cytoplasmic ERK activity is modulated into a threshold response in the nucleus.
Lysophosphatidylinositol‐acyltransferase‐1 is involved in cytosolic Ca2+ oscillations in macrophages
Authors: Takemasu Shinya , Ito Masaaki , Morioka Shin , Nigorikawa Kiyomi , Kofuji Satoshi , Takasuga Shunsuke , Eguchi Satoshi , Nakanishi Hiroki , Matsuoka Isao , Sasaki Junko , Sasaki Takehiko , Hazeki Kaoru 
Published: March 2019

AbstractLysophosphatidylinositol‐acyltransferase‐1 (LPIAT1) specifically catalyzes the transfer of arachidonoyl‐CoA to lysophosphoinositides. LPIAT−/− mice have been shown to have severe defects in the brain and liver; however, the exact molecular mechanisms behind these conditions are not well understood. As immune cells have been implicated in liver inflammation based on disfunction of LPIAT1, we generated Raw264.7 macrophages deficient in LPIAT1, using shRNA and CRISPR/Cas9. The amount of C38:4 species in phosphoinositides, especially in PtdInsP2, was remarkably decreased in these cells. Unlike in wild‐type cells, LPIAT1‐deficient cells showed prolonged oscillations of intracellular Ca2+ upon UDP stimulation, which is known to activate phospholipase Cβ through the Gq‐coupled P2Y6 receptor, even in the absence of extracellular Ca2+. It is speculated that the prolonged Ca2+ response may be relevant to the increased risk of liver inflammation induced by LPIAT1 disfunction.
Metabolic regulation of inflammasomes in inflammation
Authors: Yang Qiuli , Liu Ruichen , Yu Qing , Bi Yujing , Liu Guangwei 
Published: March 2019

Summary
Inflammasome activation and subsequent inflammatory cytokine secretion are essential for innate immune defence against multiple stimuli and are regarded as a link to adaptive immune responses. Dysfunction of inflammasome activation has been discovered at the onset or progression of infectious diseases, autoimmune diseases and cancer, all of which are also associated with metabolic factors. Furthermore, many studies concerning the metabolic regulation of inflammasome activation have emerged in recent years, especially regarding the activity of the NLRP3 inflammasome under metabolic reprogramming. In this review, we discuss the molecular mechanisms of the interactions between metabolic pathways and inflammasome activation, which exerts further important effects on various diseases.