bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gut mucosa alterations and loss of segmented filamentous bacteria in type 1 diabetes are associated with inflammation rather than hyperglycaemia
Authors: Rouland Matthieu , Beaudoin Lucie , Rouxel Ophélie , Bertrand Léo , Cagninacci Lucie , Saffarian Azadeh , Pedron Thierry , Gueddouri Dalale , Guilmeau Sandra , Burnol Anne-Françoise , Rachdi Latif , Tazi Asmaa , Mouriès Juliette , Rescigno Maria , Vergnolle Nathalie , Sansonetti Philippe , Christine Rogner Ute , Lehuen Agnès 
Published: February 2021

ObjectiveType 1 diabetes (T1D) is an autoimmune disease caused by the destruction of pancreatic β-cells producing insulin. Both T1D patients and animal models exhibit gut microbiota and mucosa alterations, although the exact cause for these remains poorly understood. We investigated the production of key cytokines controlling gut integrity, the abundance of segmented filamentous bacteria (SFB) involved in the production of these cytokines, and the respective role of autoimmune inflammation and hyperglycaemia.DesignWe used several mouse models of autoimmune T1D as well as mice rendered hyperglycaemic without inflammation to study gut mucosa and microbiota dysbiosis. We analysed cytokine expression in immune cells, epithelial cell function, SFB abundance and microbiota composition by 16S sequencing. We assessed the role of anti-tumour necrosis factor α on gut mucosa inflammation and T1D onset.ResultsWe show in models of autoimmune T1D a conserved loss of interleukin (IL)-17A, IL-22 and IL-23A in gut mucosa. Intestinal epithelial cell function was altered and gut integrity was impaired. These defects were associated with dysbiosis including progressive loss of SFB. Transfer of diabetogenic T-cells recapitulated these gut alterations, whereas induction of hyperglycaemia with no inflammation failed to do so. Moreover, anti-inflammatory treatment restored gut mucosa and immune cell function and dampened diabetes incidence.ConclusionOur results demonstrate that gut mucosa alterations and dysbiosis in T1D are primarily linked to inflammation rather than hyperglycaemia. Anti-inflammatory treatment preserves gut homeostasis and protective commensal flora reducing T1D incidence.
PD-L1 expression by Tumor Proportion Score (TPS) and Combined Positive Score (CPS) are similar in non-small cell lung cancer (NSCLC)
Authors: De Marchi Pedro , Leal Leticia Ferro , Duval da Silva Vinicius , da Silva Eduardo Caetano Albino , Cordeiro de Lima Vladmir Claudio , Reis Rui Manuel 
Published: February 2021

BackgroundFor non-small cell lung cancer (NSCLC) the most used method for analysing programmed cell death ligand 1 (PD-L1) expression is the Tumor Proportion Score (TPS). Nevertheless, for other tumour types, the Combined Positive Score (CPS) has been the method of choice.AimEvaluate and compare the predictive value of both CPS and TPS as predictors of immunotherapy response in NSCLC, and to evaluate the agreement intra-observer between both methods and inter-observer between two expert lung pathologists.Methods56 NSCLC patients who were treated with anti-programmed cell death 1 (PD-1)/PD-L1 therapy were included. Two pathologists evaluated all cases independently, considering the sample’s adequacy for analysis, and the PD-L1 expression by TPS and CPS.ResultsThe Kappa coefficient for adequacy was 0.82 (95% CI 0.67 to 0.97). There was a high agreement between TPS and CPS and a high agreement between pathologists concerning the two methods. The Kappa coefficient between TPS and CPS was 0.85 for both pathologists, and between pathologists was 0.94 and 0.93 for TPS and CPS, respectively.ConclusionsBoth methods proved to be equally predictive of response to anti-PD-1/PD-L1 therapy. There was both a high intra-observer agreement between the two methods and a high inter-observer agreement between pathologists. This study suggests that CPS could also be used in a routine setting for immunotherapy decision in NSCLC.
Interventions that improve adherence to antihypertensive medications in coronary heart disease patients: a systematic review
Authors: Hong Jialin , Tiu Yuen Chak , Leung Po Yat Bowie , Wong Man Fai , Ng Wing Yan , Cheung Dawn , Mok Hiu Yan , Lam Wai Yan , Li Kwan Yu , Wong Carlos K H 
Published: February 2021

AbstractA systematic review is conducted to identify effective interventions that improved adherence to antihypertensive drugs among patients with coronary heart diseases (CHDs). Primary studies designed to measure interventions to improve adherence on antihypertensive drugs in patients with CHD were included. Three online databases, COCHRANE, EMBASE and MEDLINE, were searched for primary studies published in English from 2005 to 2019. Studies were screened independently for eligibility. Cochrane risk-of-bias tool and the Newcastle-Ottawa Scale were used for quality assessment of randomised controlled trials (RCTs) and non-randomised studies, respectively. Of the 2000 entries identified, seven articles, including one cross-sectional study and six RCTs, met the inclusion criteria and were reviewed. One of the articles evaluated two interventions, so eight interventions were evaluated in total. Quality of the included studies was generally high, with the cross-sectional study rated as having good quality under Newcastle-Ottawa Scale, while four and two RCTs were rated as having low and some risk of bias under Cochrane risk-of-bias tool, respectively. Six of the intervention programmes were considered effective. An intervention was considered effective if it is associated with a significant (p≤0.05) and non-trivial (Cohen's d≥0.2) improvement in compliance-related outcomes such as in terms of the Morisky 8-item Medication Adherence Scale. Medication education, disease education, health education, constant reminders and medications dispensed using blister packs were identified to be effective in improving patients' compliance to medications. The importance of the continuity of interventions was also established. It is recommended that health service institutions should provide continuous education programmes, daily reminders and regular follow-ups for their patients who have CHD. It is recommended that further research ought to be carried out by using only one intervention in each trial with a standardised outcome measure, or using factorial designs, so that further cost-effectiveness evaluation of each intervention can be carried out independently, leading to the formulation of a comprehensive, optimised intervention programme for patients with CHD taking antihypertensives.
Association between fluid-attenuated inversion recovery vascular hyperintensity and outcome varies with different lesion patterns in patients with intravenous thrombolysis
Authors: Wang Erling , Wu Chuanjie , Yang Dandan , Zhao Xihai , Zhao Jie , Chang Hong , Yang Qi 
Published: February 2021

Background and purposeTo evaluate relationship between fluid-attenuated inversion recovery vascular hyperintensity (FVH) after intravenous thrombolysis and outcomes in different lesion patterns on diffusion-weighted imaging (DWI).MethodsPatients with severe internal carotid or intracranial artery stenosis who received intravenous thrombolysis from March 2012 to April 2019 were analysed. They were divided into four groups by DWI lesion patterns: border-zone infarct (BZ group), multiple lesions infarct (ML group), large territory infarct (LT group), and single cortical or subcortical lesion infarct (SL group). Logistic regression was performed to identify risk factors for outcome (unfavourable outcome, modified Rankin Scale (mRS) ≥2; poor outcome, mRS ≥3).ResultsFinally, 203 participants (63.3±10.2 years old; BZ group, n=72; ML group, n=64; LT group, n=37; SL group, n=30) from 1190 patient cohorts were analysed. After adjusting for confounding factors, FVH (+) was associated with unfavourable outcome in total group (OR 3.02; 95% CI 1.49 to 6.13; p=0.002), BZ group (OR 4.22; 95% CI 1.25 to 14.25; p=0.021) and ML group (OR 5.44; 95% CI 1.41 to 20.92; p=0.014) patients. FVH (+) was associated with poor outcome in total group (OR 2.25; 95% CI 1.01 to 4.97; p=0.046), BZ group (OR 5.52; 95% CI 0.98 to 31.07; p=0.053) and ML group (OR 4.09; 95% CI 1.04 to 16.16; p=0.045) patients, which was marginal significance. FVH (+) was not associated with unfavourable or poor outcome in LT and SL groups.ConclusionThis study suggests that association between FVH and outcome varies with different lesion patterns on DWI. The presence of FVH after intravenous thrombolysis may help to identify patients who require close observations in the hospitalisation in patients with border-zone and multiple lesion infarcts.
Remodeling of ipsilateral ulnar artery after radial artery harvesting for coronary artery bypass graft
Authors: Lima Melchior L. , Silva Héber S.M. , Lougon Lourival N. , Barros Fanilda S. , Gomes Walter J. 
Published: February 2021

There are controversies in the literature on the blood supply to the forearm after surgical removal of the radial artery in coronary artery bypass grafting (CABG). The objective was to investigate the arterial remodeling of the ulnar artery after the removal of the radial artery in myocardial revascularization by means of ultrasound examination with color Doppler in the pre- and post-operative periods. This paper describes an observational prospective study of the remodeling of the left brachial and ulnar arteries (donor arm) in 103 right-handed non-consecutive adult patients undergoing CABG with removal of the ipsilateral radial artery using the color Doppler ultrasound examination. In the ulnar artery, a significant increase (P < 0.05) was seen in the following measurements: lumen diameter by 13%, lumen area by 26%, peak systolic flow by 40%, and average flow by 46%. Intima-media thickness measured in the ulnar artery did not show a statistically significant difference (P = 0.22), except in diabetic patients (P = 0.007). We conclude that the ulnar artery undergoes positive physiological remodeling, adapting to the new requirements of chronic increase in flow after the ipsilateral removal of the radial artery to serve as a graft in CABG. There was no evidence of increased intima-media thickness, except in diabetic patients.
DQR: An Efficient Deep Q-Based Routing Approach in Multi-Controller Software Defined WAN (SD-WAN)
Authors: MAJDOUB MANEL , EL KAMEL ALI , YOUSSEF HABIB 
Published: February 2021

Software Defined Networking (SDN) is a promising paradigm in the field of network technology. This paradigm suggests the separation between the control plane and the data plane which brings flexibility, efficiency and programmability to network resources. SDN deployment in large scale networks raises many issues which can be overcame using a collaborative multi-controller approaches. Such approaches can resolve problems of routing optimization and network scalability. In large scale networks, such as SD-WAN, routing optimization consists of achieving a trade-off between per-flow QoS, the load balancing in each domain as well as the resource utilization in inter-domain links. Multi-Agent Reinforcement Learning paradigm(MARL) is one of the most popular solutions that can be used to optimize routing strategies in SD-WAN. This paper proposes an efficient approach based on MARL which is able to ensure a load balancing among each network as well as optimized resource utilization of inter-domain links. This approach profits from our previous work, denoted SPFLR, and tries to balance the load of the whole network using Deep Q-Networks (DQN) algorithms. Simulation results show that the proposed solution performs better than parallel solutions such as BGP-based routing and random routing.
Mitochondrial Inhibitor Atovaquone Increases Tumor Oxygenation and Inhibits Hypoxic Gene Expression in Patients with Non–Small Cell Lung Cancer
Authors: Skwarski Michael , McGowan Daniel R. , Belcher Elizabeth , Di Chiara Francesco , Stavroulias Dionisios , McCole Mark , Derham Jennifer L. , Chu Kwun-Ye , Teoh Eugene , Chauhan Jagat , O’Reilly Dawn , Harris Benjamin H.L. , Macklin Philip S. , Bull Joshua A. , Green Marcus , Rodriguez-Berriguete Gonzalo , Prevo Remko , Folkes Lisa K. , Campo Leticia , Ferencz Petra , Croal Paula L. , Flight Helen , Qi Cathy , Holmes Jane , O’Connor James P.B. , Gleeson Fergus V. , McKenna W. Gillies , Harris Adrian L. , Bulte Daniel , Buffa Francesca M. , Macpherson Ruth E. , Higgins Geoff S. 
Published: February 2021

Abstract

Purpose:
Tumor hypoxia fuels an aggressive tumor phenotype and confers resistance to anticancer treatments. We conducted a clinical trial to determine whether the antimalarial drug atovaquone, a known mitochondrial inhibitor, reduces hypoxia in non–small cell lung cancer (NSCLC).

Patients and Methods:
Patients with NSCLC scheduled for surgery were recruited sequentially into two cohorts: cohort 1 received oral atovaquone at the standard clinical dose of 750 mg twice daily, while cohort 2 did not. Primary imaging endpoint was change in tumor hypoxic volume (HV) measured by hypoxia PET-CT. Intercohort comparison of hypoxia gene expression signatures using RNA sequencing from resected tumors was performed.

Results:
Thirty patients were evaluable for hypoxia PET-CT analysis, 15 per cohort. Median treatment duration was 12 days. Eleven (73.3%) atovaquone-treated patients had meaningful HV reduction, with median change −28% [95% confidence interval (CI), −58.2 to −4.4]. In contrast, median change in untreated patients was +15.5% (95% CI, −6.5 to 35.5). Linear regression estimated the expected mean HV was 55% (95% CI, 24%–74%) lower in cohort 1 compared with cohort 2 (P = 0.004), adjusting for cohort, tumor volume, and baseline HV. A key pharmacodynamics endpoint was reduction in hypoxia-regulated genes, which were significantly downregulated in atovaquone-treated tumors. Data from multiple additional measures of tumor hypoxia and perfusion are presented. No atovaquone-related adverse events were reported.

Conclusions:
This is the first clinical evidence that targeting tumor mitochondrial metabolism can reduce hypoxia and produce relevant antitumor effects at the mRNA level. Repurposing atovaquone for this purpose may improve treatment outcomes for NSCLC.
Regional Changes in Patterns of Stroke Presentation During the COVID-19 Pandemic
Authors: Etherton Mark R. , Zachrison Kori S. , Yan Zhiyu , Sveikata Lukas , Bretzner Martin , Estrada Juan , Viswanathan Anand , Singhal Aneesh B. , Schwamm Lee H. 
Published: February 2021

Background and Purpose:
Patient care-seeking has likely changed during the coronavirus disease 2019 (COVID-19) pandemic. In stroke, delayed or avoided care may translate to substantial morbidity. We sought to determine the effect of the pandemic on patterns of stroke patient presentation and quality of care.

Methods:
We analyzed data from 25 New England hospitals: one urban, academic comprehensive stroke center and telestroke hub, and 24 spoke hospitals in the telestroke network. We included all telestroke consultations from the 24 spokes, and all stroke admissions to the comprehensive stroke center hub from November 1, 2019 through April 30, 2020. We compared rates of presentation, timeliness presentation, and quality of care pre- versus post-March 1, 2020. We examined trends in patient demographics, stroke severity, timeliness, diagnoses including large vessel occlusion, alteplase use, and endovascular thrombectomy among eligible subjects. We compared proportions and bivariate comparisons to examine for changes pre- versus post-March 1, 2020 and used linear regression to examine trends over time.

Results:
Among 1248 patient presentations (844 telestroke consultations, 404 comprehensive stroke center admissions), telestroke consultations and ischemic stroke patient admissions decreased among the spokes and hub. Age and stroke severity were unchanged over the study period. We found no change in alteplase administration at telestroke spoke hospitals but did note a decrease in both alteplase use and thrombectomy at our comprehensive stroke center. Time metrics for patient presentation and care delivery were unchanged; however, rates of adherence for the quality measures dysphagia screening, early antithrombotic initiation, and early venous thromboembolism prophylaxis were reduced during the pandemic.

Conclusions:
In this regional analysis, we found decreasing telestroke consultations and ischemic stroke admissions, and reduced performance on stroke quality of care measures during the COVID-19 pandemic. Contrary to prior reports, we did not find an increase in thrombectomy nor decrease in clinical severity that might be expected if patients with milder symptoms avoided hospitalization.
Toxic effects of two commercial polybrominated diphenyl ethers on Artemia larvae at three developmental stages
Authors: Zhang Qingtian , Guo Sifan , Hu Guikun 
Published: February 2021

Abstract
Toxic effects of two commercial products, penta-BDE (DE-71) and octa-BDE (DE-79), on larvae of the brine shrimp, Artemia, were studied. Results showed that their toxic effects were related not only to the concentration and exposure time, but also to the developmental stage of Artemia. Newly hatched Artemia nauplii showed stronger tolerance than those at metanauplius stage or pseudoadult stage, while DE-71 showed a stronger toxic effect than DE-79 to some extent. Abnormal behaviour of Artemia larvae might occur within 12 h, and sometimes mortality rates increased quickly even if there was no death within 36 h. Both DE-71 and DE-79 showed significant influences on the body length of Artemia larvae within 24 h; the higher the concentration, the stronger the inhibition. As far as a toxic testing standard is concerned, further experimental studies on the selection of Artemia population and developmental stage are essential.
Ovarian development in the freshwater crab Goyazana castelnaui (H. Milne Edwards, 1853) (Brachyura, Trichodactylidae)
Authors: Freita F. R. V. , Pinheiro A. P. , Gregati R. A. 
Published: February 2021

Abstract
The aim of the present study was to describe the stages of ovarian development in the eubrachyuran crab Goyazana castelnaui through macroscopic and microscopic analyses and estimate size at physiological sexual maturity. Four ovarian development stages have been defined in the 60 G. castelnaui females that were analysed from the São Pedro River in the municipality of Ouricurí (semiarid region of the state of Pernambuco, Brazil), between November 2011 and October 2012. The crabs were collected and sent to the Semiarid Crustaceans Laboratory of the Cariri Regional University. Each specimen was measured. Ovaries were classified using a visual scale, removed with needle-nose pincers, fixed, and processed for microscopic analysis. Gonad stages were determined macroscopically using a staining process and were confirmed by histological analysis (initial, intermediate, mature and spawned). Size at physiological sexual maturity was determined to be 37.67 mm carapace width for females of this species.
At Men Dan Toch Echt Uit Kalebassen? Proto-Bantoe en de Domesticatie van Cucurbitacreae.
Authors: Bulkens Annelies 
Published: February 2021

Eating out of Calabashes, Was it Reality? Proto-Bantu and the Domestication of Cucurbits
This paper examines the history of calabashes in the Bantu-world. Due to conservation problems of floral remains in tropical areas, no material traces of these fruits have been excavated untill now. The historical linguistic approach adopted in this paper, gives an overview of the evolution and history of different words signifying calabash and allows the formulation of some conclusions on agricultural history.
Climatological Teleconnections with Wind Energy in a Midcontinental Region
Authors: Coburn Jacob 
Published: February 2021

AbstractVariations in wind resources affect the reliability and feasibility of wind energy. At longer time scales, modes within the climate system and externally forced variability become important as the decadelong lifetimes of wind installations and upfront investment costs are considered. Understanding the influence of teleconnections may yield important insights for skillful seasonal predictions. In this study, several modes of variability, including the Arctic Oscillation (AO), El Niño–Southern Oscillation (ENSO), and the global surface solar flux, are assessed for their influence on wind energy anomalies in the upper Midwest (40°–52°N, 87°–105°W). Monthly wind energy is calculated using extrapolated 80-m wind fields from reanalysis data for the period 1980–2018. A multiple linear regression analysis is conducted for the monthly turbine energy output anomalies (TEOA) against the effects of synoptic patterns and pressure gradients, as well as the teleconnection indices, for each grid cell and season, yielding information on the spatial and temporal variations in influence throughout the region. The regression model indicated that each of the factors had significant influences on wind energy, although the effects varied spatially and by season. Periods of extremely low production are often embedded in prolonged declines over several months that were the result of a combination of synoptic variability and significant phases of the teleconnections such as large El Niño events, negative AO episodes, and volcanically induced reductions in surface solar flux. Monthly TEOA are found to vary by up to 37%, amounting to ±130 MW h and tens of thousands of dollars per turbine.
Dermal Regeneration Template and Staged Skin Grafting for Extirpative Scalp Wound Reconstruction: A 14‐Year Experience
Authors: Maus Jacob C. , Hemal Kshipra , Khan Mija , Calder Bennett W. , Marks Malcolm W. , Defranzo Anthony J. , Pestana Ivo Alexander 
Published: February 2021

ObjectiveDermal regeneration template and staged split‐thickness skin grafting may mitigate the need for flap coverage of postoncologic scalp defects. This technique has been studied previously in small case series. We examine the effect of risk factors, surgical technique, irradiation, and dressing modalities on reconstructive outcomes in a highly comorbid patient cohort.Study DesignRetrospective review.SettingAcademic medical center.MethodsFull‐ and partial‐thickness extirpative scalp wounds reconstructed with dermal regeneration template and staged skin grafting were reviewed over a 14‐year period. Stage 1 consisted of template application following burr craniectomy in cases lacking periosteum. Stage 2 consisted of skin grafting. Negative pressure wound therapy (NPWT) was variably used to support adherence.ResultsIn total, 102 patients were analyzed (average age 74, mean follow‐up 18 months). Eighty‐one percent were American Society of Anesthesiologists class 3 or 4. Defect size averaged 56 cm2. Average skin graft take was 94.5% in full‐thickness wounds. Seven patients failed this method. Preoperative scalp irradiation was associated with major complication and delayed graft healing. Comorbidities, wound size, and burring were not associated with complication. Patients were more likely to heal with NPWT compared to bolster (hazard ratio, 1.67; 95% CI 1.01‐2.77; P =. 046). Time between stages was 6.6 days shorter when NPWT was applied (P <. 001).ConclusionDermal template and staged skin grafting is a reliable option for postcancer scalp reconstruction in poor flap candidates. Radiotherapy is associated with adverse outcomes. Negative pressure wound therapy simplifies postoperative wound care regimens and may accelerate healing.