bluuebunny/crossref_metadata_2025_split huggingface dataset:
New therapeutic strategy of hinokitiol in haemorrhagic shock‐induced liver injury
Authors: Lu Wan‐Jung , Lin Kuan‐Hung , Tseng Mei‐Fang , Yuan Kuo‐Ching , Huang Hung‐Chang , Sheu Joen‐Rong , Chen Ray‐Jade 
Published: December 2018

AbstractHaemorrhagic shock and resuscitation (HS/R) may cause global ischaemia‐reperfusion injury, which can result in systemic inflammation, multiorgan failure (particularly liver failure) and high mortality. Hinokitiol, a bioactive tropolone‐related compound, exhibits antiplatelet and anti‐inflammatory activities. Targeting inflammatory responses is a potential strategy for ameliorating hepatic injury during HS/R. Whether hinokitiol prevents hepatic injury during HS/R remains unclear. In the present study, we determined the role of hinokitiol following HS/R. The in vivo assays revealed that hinokitiol markedly attenuated HS/R‐induced hepatic injury. Hinokitiol could inhibited NF‐κB activation and IL‐6 and TNF‐α upregulation in liver tissues. Moreover, hinokitiol reduced caspase‐3 activation, upregulated Bax and downregulated Bcl‐2. These findings suggest that hinokitiol can ameliorate liver injury following HS/R, partly through suppression of inflammation and apoptosis. Furthermore, the in vitro data revealed that hinokitiol significantly reversed hypoxia/reoxygenation (H/R)‐induced cell death and apoptosis in the primary hepatocytes. Hinokitiol prevented H/R‐induced caspase‐3 activation, PPAR cleavage, Bax overexpression and Bcl‐2 downregulation. Moreover, hinokitiol attenuated H/R‐stimulated NF‐κB activation and reduced the levels of IL‐6 and TNF‐α mRNAs, suggesting that hinokitiol can protect hepatocytes from H/R injury. Collectively, our data suggest that hinokitiol attenuates liver injury following HS/R, partly through the inhibition of NF‐κB activation.
CD83+CCR7+ NK cells induced by interleukin 18 by dendritic cells promote experimental autoimmune uveitis
Authors: Fu Qiang , Man Xuejing , Wang Xin , Song Nannan , Li Yuanbin , Xue Jiangnan , Sun Yufei , Lin Wei 
Published: December 2018

AbstractNatural killer (NK) cells have been reported to play a pathological role in autoimmune uveitis. However, the mechanisms regarding NK cells in uveitis and factors that affect NK‐cell activation in this condition remain unclear. Here, we report that the number of CD3‐NK1.1+CD83+CCR7+ cells is increased in the inflamed eyes within a mouse model of experimental autoimmune uveitis (EAU), and these cells express elevated levels of NKG2D, CD69 and IFN‐γ. Adoptively transferring CD83+CCR7+NK cells aggravates EAU symptoms and increases the number of CD4+IFN‐γ+T cells and dendritic cells (DCs) within the eye. These CD83+CCR7+NK cells then promote the maturation of DCs and IFN‐γ expression within T cells as demonstrated in vitro. Furthermore, IL‐18, as primarily secreted by DCs in the eyes, is detected to induce CD83+CCR7+NK cells. In EAU mice, anti‐IL‐18R antibody treatment also decreases retinal tissue damage, as well as the number of infiltrating CD83+CCR7+NK cells, T cells and DCs in the inflamed eyes and spleens of EAU mice. These results suggest that CD83+CCR7+NK cells, as induced by IL‐18 that primarily secreted by DCs, play a critical pathological role in EAU. Anti‐IL‐18R antibody might serve as a potential therapeutic agent for uveitis through its capacity to inhibit CD83+CCR7+NK cells infiltration.
Genetic testing and surveillance guidelines in hereditary pheochromocytoma and paraganglioma
Authors: Muth A. , Crona J. , Gimm O. , Elmgren A. , Filipsson K. , Stenmark Askmalm M. , Sandstedt J. , Tengvar M. , Tham E. 
Published: December 2018

AbstractPheochromocytoma and paraganglioma (PPGL) are rare tumours and at least 30% are part of hereditary syndromes. Approximately 20% of hereditary PPGL are caused by pathogenic germ line variants in genes of the succinate dehydrogenase complex (SDHx), TMEM127 or MAX. Herein we present guidelines regarding genetic testing of family members and their surveillance based on a thorough literature review. All cases of PPGL are recommended genetic testing for germ line variants regardless of patient and family characteristics. At minimum, FH, NF1, RET, SDHB, SDHD and VHL should be tested. In addition, testing of MEN1, SDHA, SDHAF2, SDHC, TMEM127 and MAX is recommended. Healthy first‐degree relatives (and second‐degree relatives in the case of SDHD and SDHAF2 which are maternally imprinted) should be offered carrier testing. Carriers of pathogenic variants should be offered surveillance with annual biochemical measurements of methoxy‐catecholamines and bi‐annual rapid whole‐body magnetic resonance imaging and clinical examination. Surveillance should start 5 years before the earliest age of onset in the family and thus only children eligible for surveillance should be offered pre‐symptomatic genetic testing. The surveillance of children younger than 15 years needs to be individually designed. Our guidelines will provide a framework for patient management with the possibility to follow outcome via national registries and/or follow‐up studies. Together with improved insights into the disease, this may enable optimisation of the surveillance scheme in order to minimise both anxiety and medical complications while ensuring early disease detection.
Multilocus phylogeny and taxonomy of pikas of the subgenus Ochotona (Lagomorpha, Ochotonidae)
Authors: Lissovsky Andrey A. , Yatsentyuk Svetlana P. , Koju Narayan P. 
Published: December 2018

AbstractA complete set of pika taxa, belonging to the subgenus Ochotona, was studied using craniometric and multilocus genetic analyses. We examined 1,007 skulls, covering the entire distribution range of the subgenus, as well as the mitochondrial COI gene and three nuclear introns in 31 specimens, representing nearly all taxa in question. An additional set of 167 COI gene sequences and 357 cytb gene sequences was analysed to enlarge the geographical extent of genetic data and to compare the results with previous publications. We found that the subgenus consists of eight species. One of them, Ochotona morosa, is elevated to the full species rank for the first time. The name of this species is given preliminarily and should be studied additionally. Several cases of interspecies hybridisation were found, which indicates that mitochondrial DNA cannot be used for species identification in this subgenus. Taxon Ochotona qionglaiensis, which was recently described as a separate species, represents a relic mitochondrial lineage of Ochotona thibetana. Another recently described species, Ochotona yarlungensis, is a Nubra pika with its native mitochondrial DNA, firstly found for this species. Intraspecies variation was analysed for several species for the first time. Thus, new subspecies (Ochotona thibetana fengii ssp. n.) was found within O. thibetana.
Perilipin‐2 promotes obesity and progressive fatty liver disease in mice through mechanistically distinct hepatocyte and extra‐hepatocyte actions
Authors: Orlicky David J. , Libby Andrew E. , Bales Elise S. , McMahan Rachel H. , Monks Jenifer , La Rosa Francisco G. , McManaman James L. 
Published: December 2018

Key points
Wild‐type mice and mice with hepatocyte‐specific or whole‐body deletions of perilipin‐2 (Plin2) were used to define hepatocyte and extra‐hepatocyte effects of altered cellular lipid storage on obesity and non‐alcoholic fatty liver disease (NAFLD) pathophysiology in a Western‐diet (WD) model of these disorders.
Extra‐hepatocyte actions of Plin2 are responsible for obesity, adipose inflammation and glucose clearance abnormalities in WD‐fed mice.
Hepatocyte and extra‐hepatic actions of Plin2 mediate fatty liver formation in WD‐fed mice through distinct mechanisms.
Hepatocyte‐specific actions of Plin2 are primary mediators of immune cell infiltration and fibrotic injury in livers of obese mice.
AbstractNon‐alcoholic fatty liver disease (NAFLD) is an obesity‐ and insulin resistance‐related metabolic disorder with progressive pathology. Perilipin‐2 (Plin2), a ubiquitously expressed cytoplasmic lipid droplet scaffolding protein, is hypothesized to contribute to NAFLD in humans and rodent models through effects on cellular lipid metabolism. In this study, we delineate hepatocyte‐specific and extra‐hepatocyte Plin2 mechanisms regulating the effects of obesity and insulin resistance on NAFLD pathophysiology in mice fed an obesogenic Western‐style diet (WD). Total Plin2 deletion (Plin2‐Null) fully protected WD‐fed mice from obesity, insulin resistance, adipose inflammation, steatohepatitis (NASH) and liver fibrosis found in WT animals. Hepatocyte‐specific Plin2 deletion (Plin2‐HepKO) largely protected against NASH and fibrosis and partially protected against steatosis in WD‐fed animals, but it did not protect against obesity, insulin resistance, or adipose inflammation. Significantly, total or hepatocyte‐specific Plin2 deletion impaired WD‐induced monocyte recruitment and pro‐inflammatory macrophage polarization found in livers of WT mice. Analyses of the molecular and cellular processes mediating steatosis, inflammation and fibrosis identified differences in total and hepatocyte‐specific actions of Plin2 on the mechanisms promoting NAFLD pathophysiology. Our results demonstrate that hepatocyte‐specific actions of Plin2 are central to the initiation and pathological progression of NAFLD in obese and insulin‐resistant mice through effects on immune cell recruitment and fibrogenesis. Conversely, extra‐hepatocyte Plin2 actions promote NAFLD pathophysiology through effects on obesity, inflammation and insulin resistance. Our findings provide new insight into hepatocyte and extra‐hepatocyte mechanisms underlying NAFLD development and progression.
Optic nerve appearance as a predictor of visual outcome in patients with idiopathic intracranial hypertension
Authors: Micieli Jonathan A , Bruce Beau B , Vasseneix Caroline , Blanch Richard J , Berezovsky Damian E , Peragallo Jason H , Newman Nancy J , Biousse Valérie 
Published: December 2018

Background/aimsIt remains unclear whether the presence of optic disc haemorrhages (ODH) or cotton wool spots (CWS) at presentation in patients with papilloedema from idiopathic intracranial hypertension (IIH) has prognostic value. The aim of this study was to determine if optic disc appearance at presentation predicts visual outcome in patients with IIH.MethodsRetrospective study of 708 eyes of 360 consecutive patients with IIH who had baseline optic disc photographs before or within 30 days of their diagnostic lumbar puncture and initiation of medical treatment. Optic disc photographs were independently graded by three ophthalmologists in a standardised manner. Visual function was assessed using Snellen converted to logMAR visual acuity, Humphrey mean deviation and visual field grade.ResultsAt least one ODH was found in 201 (28.4%) eyes, at least one CWS was found in 101 (14.3%) eyes and 88 eyes had both ODH and CWS (12.4%). At presentation, Frisén grade was associated with the presence and severity of ODH and CWS (p<0.001). ODH were associated with a worse visual acuity and CWS were associated with a worse visual field grade and mean deviation at presentation (p<0.05). Frisén grade was associated with worse visual function at presentation and final follow-up (p<0.001). Neither ODH nor CWS at presentation were associated with visual function at final follow-up when controlling for the Frisén grade.Conclusions and relevanceODH and CWS at baseline are not independent predictors of final visual function in IIH when controlling for the severity of papilloedema.
Appraising the value of evidence generation activities: an HIV modelling study
Authors: Woods Beth , Rothery Claire , Anderson Sarah-Jane , Eaton Jeffrey W , Revill Paul , Hallett Timothy B , Claxton Karl 
Published: December 2018

IntroductionThe generation of robust evidence has been emphasised as a priority for global health. Evidence generation spans a wide range of activities including clinical trials, surveillance programmes and health system performance measurement. As resources for healthcare and research are limited, the desirability of research expenditure should be assessed on the same basis as other healthcare resources, that is, the health gains from research must be expected to exceed the health opportunity costs imposed as funds are diverted to research rather than service provision.MethodsWe developed a transmission and costing model to examine the impact of generating additional evidence to reduce uncertainties on the evolution of a generalised HIV epidemic in Zambia.ResultsWe demonstrate three important points. First, we can quantify the value of additional evidence in terms of the health gain it is expected to generate. Second, we can quantify the health opportunity cost imposed by research expenditure. Third, the value of evidence generation depends on the budgetary policies in place for managing HIV resources under uncertainty. Generating evidence to reduce uncertainty is particularly valuable when decision makers are required to strictly adhere to expenditure plans and when transfers of funds across geographies/programmes are restricted.ConclusionBetter evidence can lead to health improvements in the same way as direct delivery of healthcare. Quantitative appraisals of evidence generation activities are important and should reflect the impact of improved evidence on population health, evidence generation costs and budgetary policies in place.
Implementation of tranexamic acid for bleeding trauma patients: a longitudinal and cross-sectional study
Authors: Coats Timothy J , Fragoso-Iñiguez Marisol , Roberts Ian 
Published: December 2018

ObjectiveTo describe the use of tranexamic acid (TXA) in trauma care in England and Wales since the Clinical Randomization of an Antifibrinolytic in Significant Hemorrhage (CRASH-2) trial results were published in 2010.MethodsA national longitudinal and cross-sectional study using data collected through the Trauma Audit and Research Network (TARN), the clinical audit of major trauma care for England and Wales. All patients in the TARN database injured in England and Wales were included apart from those with an isolated traumatic brain injury, with a primary outcome of the proportion of patients given TXA and the secondary outcome of time to treatment.ResultsAmong 228 250 patients, the proportion of trauma patients treated with TXA increased from near zero in 2010 to 10% (4593) in 2016. In 2016, most patients (82%) who received TXA did so within 3 hours of injury, however, only 30% of patients received TXA within an hour of injury. Most (80%) of the patients who had an early blood transfusion were given TXA. Patients treated with TXA by an ambulance paramedic received treatment at a median of 49 min (IQR 33–72) compared with 111 min (IQR 77–162) for patients treated in hospital.ConclusionsThere is a low proportion of patients treated with TXA across the range of injury severity and the range of physiological indicators of severity of bleeding. Most patients receive treatment within the existing target of 3 hours from injury, however there remains the potential to further improve major trauma outcomes by the earlier treatment of a wider patient group.
Novel prognostic histopathological grading system in oral squamous cell carcinoma based on tumour budding and cell nest size shows high interobserver and intraobserver concordance
Authors: Boxberg Melanie , Bollwein Christine , Jöhrens Korinna , Kuhn Peer-Hendrik , Haller Bernhard , Steiger Katja , Wolff Klaus-Dietrich , Kolk Andreas , Jesinghaus Moritz , Weichert Wilko 
Published: December 2018

AimsSquamous cell carcinoma of the oral cavity (OSCC) is a common tumour entity with a variable, partially highly aggressive clinical course. Recently, we proposed a novel (three-tiered) clinically useful grading scheme strongly associated with patient outcome in OSCC, consisting of a sum score of the histomorphological patterns tumour budding and cell nest size which outperforms WHO based grading algorithms currently in use. The aim of our study was to probe for interobserver and intraobserver reliability of this novel grading system.Methods108 OSCC were retrospectively scored according to the proposed grading scheme by three independent pathologists—two experienced head and neck pathologists and one pathologist in training—blinded to each other’s scoring results.ResultsThe Cohen’s Kappa (κ) values for concordance rates between experienced pathologists wereκ=0.97 for the overall grade,κ=0.97 for budding activity andκ=0.91 for cell nest size, indicating a strong interobserver reliability of our proposed grading system. Initial interobserver agreement was markedly lower with the pathologist in training (κ=0.55 for overall grade) but improved significantly after a training session (κ=0.87 for overall grade). Intraobserver concordance was high (κ=0.95 for overall grade), indicating a high reproducibility of the algorithm.ConclusionsIn conclusion, our study indicates that OSCC grading based on our proposed novel scheme yields an excellent inter-reader and intrareader agreement, further supporting the suitability of this grading system for routine pathological practice.
Boolean Difference Technique for Detecting All Missing Gate and Stuck-at Faults in Reversible Circuits
Authors: Mondal Joyati , Mondal Bappaditya , Kole Dipak Kumar , Rahaman Hafizur , Das Debesh Kumar 
Published: December 2018

Quantum reversible circuit is a new emerging technology attracting the researchers. A reversible circuit is composed of reversible gates. One example of reversible gate is Toffoli gate. A Toffoli gate (also known as [Formula: see text]-CNOT) has two components — the control and the target. Initially, stuck-at fault and other fault models were used for modeling defects in quantum reversible circuits. Later, a new fault model known as missing gate fault model was introduced, which is more effective in capturing the errors in quantum reversible circuit. Boolean Difference is already a known technique to detect stuck-at faults in conventional CMOS circuit. In this paper, Boolean Difference method is applied to derive the test set for detecting each stuck-at fault and missing gate fault in a reversible circuit. Then an optimization algorithm is used to derive an optimal test set, which will detect all possible faults in a circuit. The method is valid also for other fault models.
Begonia austrovietnamica (sect. Alicida, Begoniaceae), a handsome new species from South Vietnam
Authors: PENG CHING-I , TRUONG NGUYEN-DONG , NGUYEN DANH-DUC , LIN CHE-WEI 
Published: December 2018

Begonia austrovietnamica C.-I Peng, C.W. Lin, D.D. Nguyen & N.D. Truong, a new species from Binh Thuan provice, southern Vietnam, is hereby described and illustrated. B. austrovietnamica resembles B. alicida C.B. Clarke in being a tuberous species with a dormant period, having 4-tepaled staminate flowers and 3-locular ovaries. However, the new species differs from B. alicida in being stemless with basal leaves (vs. erect stem), strongly asymmetrical (vs. slightly asymmetrical) lamina, inflorescence axillary (vs. terminal), pistillate flowers 6-tepaled (vs. 5-tepaled), ovary narrowly trigonous-ellipsoid (vs. trigonous-spheroid).
Are serum autoantibodies associated with brain changes in systemic lupus erythematosus? MRI data from the Leiden NP-SLE cohort
Authors: Magro-Checa C. , Kumar S. , Ramiro S. , Beaart-van de Voorde L.J. , Eikenboom J. , Ronen I. , de Bresser J , van Buchem M.A , Huizinga T.W. , Steup-Beekman G.M. 
Published: December 2018

Objective The effect of serum autoantibodies on the brain of systemic lupus erythematosus (SLE) patients remains unclear. We investigated whether serum autoantibodies, individually and assessed in groups, are associated with specific brain-MRI abnormalities or whether these structural changes are associated with other SLE-related or traditional cardiovascular disease risk factors. Methods All patients underwent brain 3Tesla-MRI. White matter hyperintensities (WMHs), ischemic lesions, inflammatory-like lesions and cerebral atrophy were scored. Serum autoantibodies analyzed included lupus anticoagulant (LAC), anticardiolipine (aCL) IgG and IgM (first 3 also grouped into antiphospholipid autoantibodies (aPL)), anti-dsDNA, anti-SSA, anti-SSB, anti-RNP, and anti-Sm (the latter 5 grouped into SLE-related autoantibodies). Associations were assessed using logistic regression analysis adjusted for potential confounders. Furthermore, a sensitivity analysis including anti-Beta2 glycoprotein-1 antibodies (anti-β2GP1) in the aPL group was performed and the potential modification role of the neuropsychiatric clinical status in the model was assessed. Results 325 patients (mean age 42 years (SD 14), 89% female) were included. The following MRI-brain abnormalities were found: WMHs (71%), lacunar infarcts (21%), gliosis (11%), micro-hemorrhages (5%), large hemorrhages (2%), inflammatory-like lesions (6%) and atrophy (14%). No associations were found between individual or total SLE-related autoantibodies and inflammatory-like lesions. A higher number of positive aPL was associated with lacunar infarcts (OR 1.37 (95%CI 1.02–1.99) and gliosis (OR 2.15 (1.37–3.37)). LAC was associated with lacunar infarcts in white matter (OR 3.38 (1.32–8.68)) and atrophy (OR 2.49 (1.01–6.15)), and aCL IgG with gliosis (OR 2.71 (1.05–7.02)). Among other variables, SLE patients with hypertension presented a higher chance for WMHs (OR 5.61 (2.52–12.48)) and lacunar infarcts in WM (OR 2.52 (1.10–5.74)) and basal ganglia (OR 8.34 (2.19–31.70)), while cumulative SLE-damage was correlated with lacunar infarcts in WM (OR 1.43 (1.07–1.90)), basal ganglia (OR 1.72 (1.18–2.51)) and cerebellum (OR 1.79 (1.33–2.41)). These associations were confirmed in the sensitivity analysis. Conclusions Brain abnormalities in SLE represent different underlying pathogenic mechanisms. aPL are associated with ischemic brain changes in SLE, while the presence of SLE-related serum autoantibodies is not related to inflammatory-like lesions. Hypertension and cumulative SLE-damage associate with ischemic MRI-brain changes in SLE, suggesting the importance of accelerated atherosclerosis in this process.
Invasive fungal disease in patients with systemic lupus erythematosus from Southern China: a retrospective study
Authors: Lao M. , Wang X. , Ding M. , Yang Z. , Chen H. , Liang L. , Zhan Z. , Chen D. 
Published: December 2018

Objective To investigate the characteristics and associated factors of invasive fungal disease in patients with systemic lupus erythematosus from Southern China. Methods A retrospective study was performed. Demographic and clinical characteristics, laboratory data, and radiographic manifestations were recorded. Results A total of 45 lupus patients with invasive fungal disease (incidence 1.1%) were included. Twenty-three cases (51.1%) were infected with mold and 22 cases (48.9%) with yeast. Aspergillus spp. (44.4%) and Cryptococcus spp. (33.3%) were common. Aspergillosis mainly occurred in the lung. Cryptococcosis developed in the lung (40.0%), meninges (46.7%) and bloodstream (13.3%). Compared with yeast infection, mold infection tended to develop in patients with active lupus nephritis (65.2% vs. 31.8%, P = 0.03) and the mortality rate was higher (20.0% vs. 0%, P = 0.001). Co-infection with bacteria, virus or superficial fungi occurred in 12 patients (26.7%). Multivariate logistic regression analysis indicated that lymphopenia (odds ratio 2.65, 95% confidential interval 1.14–6.20, P = 0.02) and an accumulated dose of glucocorticoid (odds ratio 1.58, 95% confidence interval 1.10–2.25, P = 0.01) was associated with invasive fungal disease in lupus patients. Conclusion Mold infection tended to develop in patients with active lupus disease with high mortality. Co-infection is not rare. Lymphopenia and an accumulated dose of glucocorticoid are associated with invasive fungal disease in lupus patients.