bluuebunny/crossref_metadata_2025_split huggingface dataset:
Natural history of renal tumours in von Hippel-Lindau disease: a large retrospective study of Chinese patients
Authors: Peng Xiang , Chen Jinchao , Wang Jiangyi , Peng Shuanghe , Liu Shengjie , Ma Kaifang , Zhou Jingcheng , Hong Baoan , Zhou Bowen , Zhang Jiufeng , Cai Lin , Gong Kan 
Published: February 2019

BackgroundHistorically, renal cell carcinoma (RCC) is one of the main causes of death in von Hippel-Lindau (VHL) disease. However, the natural history of VHL-related RCC has not been thoroughly elucidated to date. This report described the natural history of VHL-related RCC in a large Chinese VHL cohort and might be helpful in the surveillance and treatment of VHL disease.MethodsIn this retrospective study, we included 196 renal tumours from 150 patients with VHL disease. Statistical analysis was used to evaluate the influence of age of onset, sex, family history, unilateral or bilateral tumour, VHL disease type, mutation type, mutation location, and tumour size on tumour growth, metastasis and survival in patients with VHL disease.ResultsThe mean age of onset was 38.8 years, and the mean initial tumour size was 3.1 cm. The mean linear growth rate was 0.49 cm/year. Patients experienced faster tumour growth when they had later age of onset, larger initial tumour size, missense mutation, mutations locating in exon 3, and when they were not affected by cerebral or retinal haemangioblastomas. Tumours larger than 4 cm grew faster than those smaller than 4 cm. Bilateral tumours, large initial tumours, fast tumour growth and metastasis were risk factors for poor prognosis in VHL-related RCC.ConclusionThis large study demonstrated that age of onset, initial tumour size, concomitant tumours, mutation type and mutation location had an effect on growth rate in VHL-related RCC. Active surveillance may be safe for patients with tumour size less than 4 cm, which is helpful in clinical decision-making.
Coupling phenomenon of anti-connected hybrid alignment nematics in thin cell: From submicron to nanoscale
Authors: Chen Sibo , Liu Xiaoting , Yu Huimin , Zhou Xuan , Zhang Zhidong 
Published: February 2019

Within Landau–de Gennes theory, we modeled a system consisting of two anti-connected hybrid alignment nematics (HAN). Our numerical simulation results indicated the occurrence of four states denoted as I, II, III and IV. The states undergo a structure transition as a function of the cell gap d. For d [Formula: see text] d0, where d0is the maximum value for the structure transition to occur, state I and II are bistable, whereas state III and IV are metastable and quadruply degenerate. We found that d0= 15[Formula: see text], where [Formula: see text] is the biaxial characteristic coherence length. When d[Formula: see text] [Formula: see text] d [Formula: see text] d0, where d[Formula: see text] = 7[Formula: see text] and d[Formula: see text] is the critical cell gap for order reconstruction (OR), continuous inversion walls appear both in state III and IV. We first found that the structure transition from inversion walls to defect walls occurs with decreasing d from the submicron to nanoscale. During this process, quadruply degenerate states in state III and IV transformed into doubly degenerate states. Meanwhile, states I and II remained bistable. When d = d[Formula: see text], all states reached a new type of OR pattern with two biaxial walls cross-linked with each other by a novel approach; i.e., from defect walls to OR.
A reconfigurable scheme for realization of electro-optical logic gate based on silicon-graphene Mach–Zhender interferometer
Authors: Zivarian Hossein , Zarifkar Abbas 
Published: February 2019

In this paper, we propose a reconfigurable scheme for implementation of an electro-optical logic gate by utilizing a Mach–Zehnder interferometer (MZI)-based structure. In order to achieve high performance and small footprint for the proposed logic gate, we have used a compact, broadband, low power and high speed MZI-based electro-optical switch which consists of a silicon-graphene slot waveguide as phase shifter in each arm of the MZI structure. Our design can perform electro-optical AND, OR and XOR logic functions in three different operational modes by using three electrical control signals. The functionality of the reconfigurable electro-optical logic gate is investigated with the help of eye diagram analysis for all three operational modes. Simulation results show that the proposed reconfigurable logic gate is able to work under at least 62.5 Gbit/s with high extinction ratio (ER) about 24.6 dB for transverse electric polarization mode at telecommunication wavelength of 1.55 [Formula: see text]m.
Low-Dose Apatinib Optimizes Tumor Microenvironment and Potentiates Antitumor Effect of PD-1/PD-L1 Blockade in Lung Cancer
Authors: Zhao Sha , Ren Shengxiang , Jiang Tao , Zhu Bo , Li Xuefei , Zhao Chao , Jia Yijun , Shi Jinpeng , Zhang Limin , Liu Xiaozhen , Qiao Meng , Chen Xiaoxia , Su Chunxia , Yu Hui , Zhou Caicun , Zhang Jun , Camidge D. Ross , Hirsch Fred R. 
Published: February 2019

Abstract
The lack of response to treatment in most lung cancer patients suggests the value of broadening the benefit of anti–PD-1/PD-L1 monotherapy. Judicious dosing of antiangiogenic agents such as apatinib (VEGFR2-TKI) can modulate the tumor immunosuppressive microenvironment, which contributes to resistance to anti–PD-1/PD-L1 treatment. We therefore hypothesized that inhibiting angiogenesis could enhance the therapeutic efficacy of PD-1/PD-L1 blockade. Here, using a syngeneic lung cancer mouse model, we demonstrated that low-dose apatinib alleviated hypoxia, increased infiltration of CD8+ T cells, reduced recruitment of tumor-associated macrophages in tumor and decreased TGFβ amounts in both tumor and serum. Combining low-dose apatinib with anti–PD-L1 significantly retarded tumor growth, reduced the number of metastases, and prolonged survival in mouse models. Anticancer activity was evident after coadministration of low-dose apatinib and anti–PD-1 in a small cohort of patients with pretreated advanced non–small cell lung cancer. Overall, our work shows the rationale for the treatment of lung cancer with a combination of PD-1/PD-L1 blockade and low-dose apatinib.
Aspectos ético-metodológicos do fazer etnográfico a partir do convívio com usuários de crack
Authors: Alves Ygor Diego Delgado , Pereira Pedro Paulo Gomes 
Published: February 2019

A etnografia em ambientes onde ocorrem práticas ilícitas, certamente nos impõem questões ético-metodológicas da maior relevância. Conviver com as pessoas, nestes casos, envolve riscos específicos, tanto ao pesquisador quanto a seus interlocutores. Incorrer em atos ilegais pode se revelar uma contingência para se permanecer no campo, onde as barreiras legais se somam aos limites fixados pelos corpos. O uso da droga é capaz de sugestionar uma ética própria que não é inerente a ela, mas condicionada por uma situação que foge radicalmente ao controle do antropólogo. Os usuários de crack se revelaram detentores de conhecimento acurado sobre sua condição de vida e bons parceiros na produção de conhecimento acadêmico a respeito deles mesmos.
“If you suspect a case of Ebola... free call 177”:
Authors: Pimenta Denise 
Published: February 2019

Nos últimos anos, tenho me debruçado sobre as questões sociais que circundam a epidemia de Ebola no Oeste Africano, mais precisamente em Serra Leoa. De outubro de 2015 a janeiro de 2016 viajei para a região, fazendo trabalho de campo tanto na capital de Serra Leoa (Freetown) quanto nos demais distritos do país. Em todo o país existiam ckeckpoints, instrumento do controle dos corpos. Além disso, por todas as cidades eram comum cartazes e outdoors mobilizando a população a se manter atenta a casos de Ebola, sugerindo inclusive “denúncias” como: “If you suspect of someone with Ebola, call 177”. Desta maneira, é notório o uso de uma linguagem militar para tratar da epidemia. Porém, a militarização não encontra-se apenas nas metáforas, partindo para o contexto das práticas diárias como ameaças, privações de liberdade como lockdowns, quarentenas e até prisões. Ou seja, o controle da epidemia sempre esteve diretamente ligado à militarização da saúde.
Angiopoietin-2 Inhibition Rescues Arteriovenous Malformation in a Smad4 Hereditary Hemorrhagic Telangiectasia Mouse Model
Authors: Crist Angela M. , Zhou Xingyan , Garai Jone , Lee Amanda R. , Thoele Janina , Ullmer Christoph , Klein Christian , Zabaleta Jovanny , Meadows Stryder M. 
Published: February 2019

Background:
Hereditary hemorrhagic telangiectasia is an autosomal dominant vascular disorder caused by heterozygous, loss-of-function mutations in 4 transforming growth factor beta (TGFβ) pathway members, including the central transcriptional mediator of the TGFβ pathway, Smad4. Loss of Smad4 causes the formation of inappropriate, fragile connections between arteries and veins called arteriovenous malformations (AVMs), which can hemorrhage leading to stroke, aneurysm, or death. Unfortunately, the molecular mechanisms underlying AVM pathogenesis remain poorly understood, and the TGFβ downstream effectors responsible for hereditary hemorrhagic telangiectasia–associated AVM formation are currently unknown.

Methods:

To identify potential biological targets of the TGFβ pathway involved in AVM formation, we performed RNA- and chromatin immunoprecipitation–sequencing experiments on BMP9 (bone morphogenetic protein 9)-stimulated endothelial cells (ECs) and isolated ECs from a Smad4-inducible, EC-specific knockout (
Smad4
-iECKO) mouse model that develops retinal AVMs. These sequencing studies identified the angiopoietin-Tek signaling pathway as a downstream target of SMAD4. We used monoclonal blocking antibodies to target a specific component in this pathway and assess its effects on AVM development.

Results:

Sequencing studies uncovered 212 potential biological targets involved in AVM formation, including the EC surface receptor, TEK (TEK receptor tyrosine kinase) and its antagonistic ligand, ANGPT2 (angiopoietin-2). In
Smad4
-iECKO mice,
Angpt2
expression is robustly increased, whereas
Tek
levels are decreased, resulting in an overall reduction in angiopoietin-Tek signaling. We provide evidence that SMAD4 directly represses
Angpt2
transcription in ECs. Inhibition of ANGPT2 function in
Smad4
-deficient mice, either before or after AVMs form, prevents and alleviates AVM formation and normalizes vessel diameters. These rescue effects are attributed to a reversion in EC morphological changes, such as cell size and shape that are altered in the absence of
Smad4.

Conclusions:

Our studies provide a novel mechanism whereby the loss of
Smad4
causes increased
Angpt2
transcription in ECs leading to AVM formation, increased blood vessel calibers, and changes in EC morphology in the retina. Blockade of ANGPT2 function in an in vivo Smad4 model of hereditary hemorrhagic telangiectasia alleviated these vascular phenotypes, further implicating ANGPT2 as an important TGFβ downstream mediator of AVM formation. Therefore, alternative approaches that target ANGPT2 function may have therapeutic value for the alleviation of hereditary hemorrhagic telangiectasia symptoms, such as AVMs.
High Levels of Soluble Lectinlike Oxidized Low‐Density Lipoprotein Receptor‐1 Are Associated With Carotid Plaque Inflammation and Increased Risk of Ischemic Stroke
Authors: Markstad Hanna , Edsfeldt Andreas , Yao Mattison Ingrid , Bengtsson Eva , Singh Pratibha , Cavalera Michele , Asciutto Giuseppe , Björkbacka Harry , Fredrikson Gunilla Nordin , Dias Nuno , Volkov Petr , Orho‐Melander Marju , Nilsson Jan , Engström Gunnar , Gonçalves Isabel 
Published: February 2019

Background

When the lectinlike oxidized low‐density lipoprotein (ox
LDL)
receptor‐1 (
LOX
‐1), a scavenger receptor for ox
LDL
, binds ox
LDL
, processes leading to endothelial dysfunction and inflammation are promoted. We aimed to study release mechanisms of
LOX
‐1 and how circulating levels of soluble
LOX
‐1 (
sLOX
‐1) relate to plaque inflammation and future risk for ischemic stroke.

Methods and Results

Endothelial cells and leukocytes were used to study release of
sLOX
‐1. Plasma levels of
sLOX
‐1 were determined in 4703 participants in the Malmö Diet and Cancer cohort. Incidence of ischemic stroke was monitored. For 202 patients undergoing carotid endarterectomy, levels of
sLOX
‐1 were analyzed in plasma and plaque homogenates and related to plaque inflammation factors. Endothelial cells released
sLOX
‐1 when exposed to ox
LDL
. A total of 257 subjects experienced stroke during a mean follow‐up of 16.5 years. Subjects in the highest tertile of
sLOX
‐1 had a stroke hazard ratio of 1.75 (95%
CI,
1.28–2.39) compared with those in the lowest tertile after adjusting for age and sex. The patients undergoing carotid endarterectomy had a significant association between plasma
sLOX
‐1 and the plaque content of
sLOX
‐1 (
r
=0.209,
P
=0.004). Plaques with high levels of
sLOX
‐1 had more ox
LDL
, proinflammatory cytokines, and matrix metalloproteinases.

Conclusions

Our findings demonstrate that ox
LDL
induces the release of
sLOX
‐1 from endothelial cells and that circulating levels of
sLOX
‐1 correlate with carotid plaque inflammation and risk for ischemic stroke. These observations provide clinical support to experimental studies implicating
LOX
‐1 in atherosclerosis and its possible role as target for cardiovascular intervention.
Cortical Cerebral Microinfarcts on 3T Magnetic Resonance Imaging in Patients With Carotid Artery Stenosis
Authors: Takasugi Junji , Miwa Kaori , Watanabe Yoshiyuki , Okazaki Shuhei , Todo Kenichi , Sasaki Tsutomu , Sakaguchi Manabu , Mochizuki Hideki 
Published: February 2019

Background and Purpose—
Carotid artery stenosis is common in the elderly and contributes to cognitive impairment and dementia. Cortical cerebral microinfarcts (CMIs) play an important role in vascular cognitive impairment and dementia. We aimed to investigate the association between CMIs on 3T magnetic resonance imaging and clinical and radiological features, including plaque morphology, and cognitive function in patients with carotid stenosis.

Methods—
Eighty-nine patients with >30% carotid stenosis on ultrasound were prospectively enrolled, and underwent brain and carotid artery magnetic resonance imaging. CMIs were rated according to predetermined criteria based on 3D-double inversion recovery and fluid-attenuated inversion recovery images.

Results—

CMIs were identified in 26 patients (29%; median number 0, range 0–9). Poisson regression models adjusted for age and sex revealed that CMIs were associated with intraplaque hemorrhage (rate ratio, 1.95; 95% CI, 1.26–3.18), lacunar infarcts (rate ratio, 1.54; 95% CI, 1.00–2.44), and cortical infarcts (rate ratio, 3.22; 95% CI, 2.20–5.00). These associations were also observed in asymptomatic patients (n=64). Of 81 patients with unilateral carotid stenosis, the prevalence and number of CMIs were significantly higher in the hemisphere ipsilateral to the carotid stenosis than in the contralateral hemisphere (
P
=0.005 and
P
<0.001, respectively). The presence of CMIs was associated with poor cognitive function.

Conclusions—
Our results indicate that vulnerable carotid plaque increases the risk of CMIs and subsequent cognitive impairment. Carotid atherosclerosis could be a potential therapeutic target for cognitive impairment.
Sleep-Disordered Breathing Is Associated With Recurrent Ischemic Stroke
Authors: Brown Devin L. , Shafie-Khorassani Fatema , Kim Sehee , Chervin Ronald D. , Case Erin , Morgenstern Lewis B. , Yadollahi Azadeh , Tower Susan , Lisabeth Lynda D. 
Published: February 2019

Background and Purpose—
Limited data are available about the relationship between sleep-disordered breathing (SDB) and recurrent stroke and mortality, especially from population-based studies, large samples, or ethnically diverse populations.

Methods—
In the BASIC project (Brain Attack Surveillance in Corpus Christ), we identified patients with ischemic stroke (2010–2015). Subjects were offered screening for SDB with the ApneaLink Plus device, from which a respiratory event index (REI) score ≥10 defined SDB. Demographics and baseline characteristics were determined from chart review and interview. Recurrent ischemic stroke was identified through active and passive surveillance. Cause-specific proportional hazards models were used to assess the association between REI (modeled linearly) and ischemic stroke recurrence (as the event of interest), and all-cause poststroke mortality, adjusted for multiple potential confounders.

Results—
Among 842 subjects, the median age was 65 (interquartile range, 57–76), 47% were female, and 58% were Mexican American. The median REI score was 14 (interquartile range, 6–26); 63% had SDB. SDB was associated with male sex, Mexican American ethnicity, being insured, nonsmoking status, diabetes mellitus, hypertension, lower educational attainment, and higher body mass index. Among Mexican American and non-Hispanic whites, 85 (11%) ischemic recurrent strokes and 104 (13%) deaths occurred, with a median follow-up time of 591 days. In fully adjusted models, REI was associated with recurrent ischemic stroke (hazard ratio, 1.02 [hazard ratio for one-unit higher REI score, 95% CI, 1.01–1.03]), but not with mortality alone (hazard ratio, 1.00 [95% CI, 0.99–1.02]).

Conclusions—
Results from this large population-based study show that SDB is associated with recurrent ischemic stroke, but not mortality. SDB may therefore represent an important modifiable risk factor for poor stroke outcomes.
Partitioning Uncertainty Components of an Incomplete Ensemble of Climate Projections Using Data Augmentation
Authors: Evin Guillaume , Hingray Benoit , Blanchet Juliette , Eckert Nicolas , Morin Samuel , Verfaillie Deborah 
Published: February 2019

AbstractThe quantification of uncertainty sources in ensembles of climate projections obtained from combinations of different scenarios and climate and impact models is a key issue in climate impact studies. The small size of the ensembles of simulation chains and their incomplete sampling of scenario and climate model combinations makes the analysis difficult. In the popular single-time ANOVA approach for instance, a precise estimate of internal variability requires multiple members for each simulation chain (e.g., each emission scenario–climate model combination), but multiple members are typically available for a few chains only. In most ensembles also, a precise partition of model uncertainty components is not possible because the matrix of available scenario/models combinations is incomplete (i.e., projections are missing for many scenario–model combinations). The method we present here, based on data augmentation and Bayesian techniques, overcomes such limitations and makes the statistical analysis possible for single-member and incomplete ensembles. It provides unbiased estimates of climate change responses of all simulation chains and of all uncertainty variables. It additionally propagates uncertainty due to missing information in the estimates. This approach is illustrated for projections of regional precipitation and temperature for four mountain massifs in France. It is applicable for any kind of ensemble of climate projections, including those produced from ad hoc impact models.
Evolution of Dynamic and Thermodynamic Structures before and during Rapid Intensification of Tropical Cyclones: Sensitivity to Vertical Wind Shear
Authors: Tao Dandan , Zhang Fuqing 
Published: February 2019

AbstractThis study explores the spatial and temporal changes in tropical cyclone (TC) thermodynamic and dynamic structures before, near, and during rapid intensification (RI) under different vertical wind shear conditions through four sets of convection-permitting ensemble simulations. A composite analysis of TC structural evolution is performed by matching the RI onset time of each member. Without background flow, the axisymmetric TC undergoes a gradual strengthening of the inner-core vorticity and warm core throughout the simulation. In the presence of moderate environmental shear (5–6 m s−1), both the location and magnitude of the asymmetries in boundary layer radial flow, relative humidity, and vertical motion evolve with the tilt vector throughout the simulation. A budget analysis indicates that tilting is crucial to maintaining the midlevel vortex while stretching and vertical advection are responsible for the upper-level vorticity generation before RI when strong asymmetries arise. Two warm anomalies are observed before the RI onset when the vortex column is tilted. When approaching the RI onset, these two warm anomalies gradually merge into one. Overall, the most symmetric vortex structure is found near the RI onset. Moderately sheared TCs experience an adjustment period from a highly asymmetric structure with updrafts concentrated at the down-tilt side before RI to a more axisymmetric structure during RI as the eyewall updrafts develop. This adjustment period near the RI onset, however, is found to be the least active period for deep convection. TC development under a smaller environmental shear (2.5 m s−1) condition displays an intermediate evolution between ensemble experiments with no background flow and with moderate shear (5–6 m s−1).
Endovascular Embolization in the Treatment of Epistaxis
Authors: Huyett Phillip , Jankowitz Brian T. , Wang Eric W. , Snyderman Carl H. 
Published: February 2019

ObjectiveThe cost‐effectiveness of endovascular embolization (EE) for intractable epistaxis has been questioned, especially as endoscopic surgical techniques have become standard of care at many institutions. Our objectives were to review the safety profile and effectiveness of EE for epistaxis.Study DesignRetrospective case series.SettingTertiary care hospital.SubjectsThere were 54 patients and 64 unique encounters. Patients were 66.7% male, with a mean age of 64.5 years. Bleeding disorders were present in 18.8%, hypertension was present in 71.7%, and 61.1% were on anticoagulant/platelet drugs.MethodsCharts of patients undergoing EE for epistaxis between 2005 and 2015 were retrospectively reviewed.ResultsThe immediate bleeding control rate was 92.6%. Three patients died within 1 week of EE and were excluded from further analysis. Overall, 64.7% of the remaining patients had no further episodes of epistaxis. Thirteen patients (25.4%) rebled within 1 week, 11 of whom required repeat EE or operative control. Five patients (9.8%) rebled more than 1 week following the procedure with 4 requiring repeat EE or operative control. The major complication rate was 7.4% and included transient stroke, diplopia, facial skin necrosis, and extraperitoneal hemorrhage.ConclusionWhile the immediate success rate of EE for epistaxis was comparable to the literature, the overall short‐ and long‐term rebleed rate was high in this selected population. The results suggest that patients who are referred for EE represent a high‐risk group with increased risk of repeat hemorrhage and morbidity. Patients who undergo EE for epistaxis should be carefully monitored for complications, including repeat hemorrhage.