bluuebunny/crossref_metadata_2025_split huggingface dataset:
Firn Evolution at Camp Century, Greenland: 1966–2100
Authors: Vandecrux Baptiste , Colgan William , Solgaard Anne M. , Steffensen Jørgen Peder , Karlsson Nanna B. 
Published: March 2021

Camp Century is an American military base built in 1959 under the surface of the Greenland ice sheet and decommissioned in 1967. Here, we use outputs from RACMO2.3p2 and CanESM2 climate models, adjusted to meteorological observations, and a firn model to simulate the firn density and temperature at Camp Century between 1966 and 2100. The model output is evaluated against an extensive set of firn 3observations and three Representative Concentration Pathways (RCP2.6, 4.5 and 8.5) are considered as future scenarios. Our model suggests that the upper horizon of the Camp Century debris field – observed at a depth of 32 m in 2017 – will continue to be buried by persistent net accumulation over the next eighty years under all RCP scenarios. This horizon depth will be between 58 and 64 m in 2100, depending on the RCP scenario. We estimate a maximum meltwater percolation depth of 1.1 m under all RCP scenarios. We therefore find it extremely unlikely that surface meltwater interacts with the subsurface debris field at Camp Century before 2100 under all RCP scenarios. Camp Century’s future is representative of the firn area in northwestern Greenland, bound to shift from dry snow to a percolation regime. Our model suggests that 10 m firn temperatures at Camp Century will increase from −24.0°C in 1966 to −21.3, −20.0 and −18.6°C in 2100 under the RCP2.6, 4.5 and 8.5 scenarios, respectively. We reveal a previously unknown warm bias in air temperatures simulated at Camp Century by both RACMO2.3p2 and CanESM2 climate models which needs to be accounted for when using these models to predict melt, firn evolution and sea-level contribution of the Greenland ice sheet. We also present novelin situmeasurements of firn compaction rates, which indicate that about 25% of firn compaction of the top 62 m of firn occurs below 20 m depth. This highlights the importance of deep-firn compaction measurements for model evaluation and correction of altimetry products.
Functional and Activation Profiles of Mucosal-Associated Invariant T Cells in Patients With Tuberculosis and HIV in a High Endemic Setting
Authors: Balfour Avuyonke , Schutz Charlotte , Goliath Rene , Wilkinson Katalin A. , Sayed Sumaya , Sossen Bianca , Kanyik Jean-Paul , Ward Amy , Ndzhukule Rhandzu , Gela Anele , Lewinsohn David M. , Lewinsohn Deborah A. , Meintjes Graeme , Shey Muki 
Published: March 2021

Background: MAIT cells are non-classically restricted T lymphocytes that recognize and rapidly respond to microbial metabolites or cytokines and have the capacity to kill bacteria-infected cells. Circulating MAIT cell numbers generally decrease in patients with active TB and HIV infection, but findings regarding functional changes differ.Methods: We conducted a cross-sectional study on the effect of HIV, TB, and HIV-associated TB (HIV-TB) on MAIT cell frequencies, activation and functional profile in a high TB endemic setting in South Africa. Blood was collected from (i) healthy controls (HC, n = 26), 24 of whom had LTBI, (ii) individuals with active TB (aTB, n = 36), (iii) individuals with HIV infection (HIV, n = 50), 37 of whom had LTBI, and (iv) individuals with HIV-associated TB (HIV-TB, n = 26). All TB participants were newly diagnosed and sampled before treatment, additional samples were also collected from 18 participants in the aTB group after 10 weeks of TB treatment. Peripheral blood mononuclear cells (PBMC) stimulated with BCG-expressing GFP (BCG-GFP) and heat-killed (HK) Mycobacterium tuberculosis (M.tb) were analyzed using flow cytometry. MAIT cells were defined as CD3+ CD161+ Vα7.2+ T cells.Results: Circulating MAIT cell frequencies were depleted in individuals with HIV infection (p = 0.009). MAIT cells showed reduced CD107a expression in aTB (p = 0.006), and reduced IFNγ expression in aTB (p &lt; 0.001) and in HIV-TB (p &lt; 0.001) in response to BCG-GFP stimulation. This functional impairment was coupled with a significant increase in activation (defined by HLA-DR expression) in resting MAIT cells from HIV (p &lt; 0.001), aTB (p = 0.019), and HIV-TB (p = 0.005) patients, and higher HLA-DR expression in MAIT cells expressing IFNγ in aTB (p = 0.009) and HIV-TB (p = 0.002) after stimulation with BCG-GFP and HK-M.tb. After 10 weeks of TB treatment, there was reversion in the observed functional impairment in total MAIT cells, with increases in CD107a (p = 0.020) and IFNγ (p = 0.010) expression.Conclusions: Frequencies and functional profile of MAIT cells in response to mycobacterial stimulation are significantly decreased in HIV infected persons, active TB and HIV-associated TB, with a concomitant increase in MAIT cell activation. These alterations may reduce the capacity of MAIT cells to play a protective role in the immune response to these two pathogens.
Reduced Endothelial Function in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome–Results From Open-Label Cyclophosphamide Intervention Study
Authors: Sørland Kari , Sandvik Miriam Kristine , Rekeland Ingrid Gurvin , Ribu Lis , Småstuen Milada Cvancarova , Mella Olav , Fluge Øystein 
Published: March 2021

Introduction: Patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) present with a range of symptoms including post-exertional malaise (PEM), orthostatic intolerance, and autonomic dysfunction. Dysfunction of the blood vessel endothelium could be an underlying biological mechanism, resulting in inability to fine-tune regulation of blood flow according to the metabolic demands of tissues. The objectives of the present study were to investigate endothelial function in ME/CFS patients compared to healthy individuals, and assess possible changes in endothelial function after intervention with IV cyclophosphamide.Methods: This substudy to the open-label phase II trial “Cyclophosphamide in ME/CFS” included 40 patients with mild-moderate to severe ME/CFS according to Canadian consensus criteria, aged 18–65 years. Endothelial function was measured by Flow-mediated dilation (FMD) and Post-occlusive reactive hyperemia (PORH) at baseline and repeated after 12 months. Endothelial function at baseline was compared with two cohorts of healthy controls (N = 66 and N = 30) from previous studies. Changes in endothelial function after 12 months were assessed and correlated with clinical response to cyclophosphamide. Biological markers for endothelial function were measured in serum at baseline and compared with healthy controls (N = 30).Results: Baseline FMD was significantly reduced in patients (median FMD 5.9%, range 0.5–13.1, n = 35) compared to healthy individuals (median FMD 7.7%, range 0.7–21, n = 66) (p = 0.005), as was PORH with patient score median 1,331 p.u. (range 343–4,334) vs. healthy individuals 1,886 p.u. (range 808–8,158) (p = 0.003). No significant associations were found between clinical response to cyclophosphamide intervention (reported in 55% of patients) and changes in FMD/PORH from baseline to 12 months. Serum levels of metabolites associated with endothelial dysfunction showed no significant differences between ME/CFS patients and healthy controls.Conclusions: Patients with ME/CFS had reduced endothelial function affecting both large and small vessels compared to healthy controls. Changes in endothelial function did not follow clinical responses during follow-up after cyclophosphamide IV intervention.
Is Fluoxetine Good for Subacute Stroke? A Meta-Analysis Evidenced From Randomized Controlled Trials
Authors: Liu Guangjie , Yang Xingyu , Xue Tao , Chen Shujun , Wu Xin , Yan Zeya , Wang Zilan , Wu Da , Chen Zhouqing , Wang Zhong 
Published: March 2021

Background and Purpose:Fluoxetine is a drug commonly used to treat mental disorders, such as depression and obsessive–compulsive disorder, and some studies have shown that fluoxetine can improve motor and function recovery after stroke. Therefore, we performed a meta-analysis to investigate the efficacy and safety of fluoxetine in the treatment of post-stroke neurological recovery.Methods:PubMed, Embase, and Cochrane Library were searched for randomized controlled trials (RCTs) that were performed to assess the efficacy and safety of fluoxetine for functional and motor recovery in subacute stroke patients up to October 2020. Review Manager 5.3 software was used to assess the data. The risk ratio (RR) and standardized mean difference (SMD) were analyzed and calculated with a fixed effects model.Results:We pooled 6,788 patients from nine RCTs. The primary endpoint was modified Rankin Scale (mRS). Fluoxetine did not change the proportion of mRS ≤ 2 (P= 0.47). The secondary endpoints were Fugl-Meyer Motor Scale (FMMS), Barthel Index (BI), and National Institutes of Health Stroke Scale (NIHSS). Fluoxetine improved the FMMS (P&lt; 0.00001) and BI(P&lt; 0.0001) and showed a tendency of improving NIHSS (P= 0.08). In addition, we found that fluoxetine reduced the rate of new-onset depression (P&lt; 0.0001) and new antidepressants (P&lt; 0.0001).Conclusion:In post-stroke treatment, fluoxetine did not improve participants' mRS and NIHSS but improved FMMS and BI. This difference could result from heterogeneities between the trials: different treatment duration, clinical scales sensitivity, patient age, delay of inclusion, and severity of the deficit.
Clinical and Radiological Characteristics of Acute Cerebrovascular Diseases Among Egyptian Patients With COVID-19 in Upper Egypt
Authors: Khedr Eman M. , Soliman Radwa K. , Abo-Elfetof Noha , Amin Mariam , Mansour Ossama Yassin , Aly Ahmed , Zaki Ahmed F. , Saber Mostafa 
Published: March 2021

Background and Purpose: There is little information on the acute cerebrovascular complications of coronavirus disease 2019 (COVID-19) in Egypt. The aim of this study was to estimate the proportion of acute cerebrovascular disease (CVD) among COVID-19 patients and evaluate their clinical and radiological characteristics in comparison with non-COVID-19 CVD.Materials and Methods: In a retrospective study, COVID-19 patients whom presented with CVD in Assiut and Aswan University Hospitals were compared with non-COVID-19, CVD patients, admitted to Qena University Hospital, prior to the pandemic. The following data were collected: clinical history and presentation, risk factors, comorbidities, brain imaging (MRI or CT), chest CT, and some laboratory investigations.Results: Fifty-five (12.5%) of the 439 patients with COVID-19 had acute CVD. Of them, 42 (9.6%) had ischemic stroke while 13 patients (2.9%) had hemorrhagic CVD. In the 250 cases of the non-COVID-19 group, 180 had ischemic stroke and 70 had hemorrhagic stroke. A large proportion of patients with COVID-19 who presented with ischemic stroke had large vessel occlusion (LVO), which was significantly higher than in non-COVID-19 patients with CVD (40 vs. 7.2%, P &lt; 0.001). Comorbidities were recorded in 44 (80%) cases. In COVID-19 ischemic stroke patients, risk factors [hypertension and ischemic heart disease (IHD)] and comorbidities (hepatic and renal) were significantly higher than those in non–COVID-19 patients. In addition, 23.5% had hemorrhagic CVD, and six patients with LVO developed hemorrhagic transformation.Conclusion: Acute CVD among patients with COVID-19 was common in our study. LVO was the commonest. Hypertension, IHD, and anemia are the most common risk factors and could contribute to the worsening of clinical presentation. Comorbidities were common among patients with CVD, although a large number had elevated liver enzymes and creatinine that were partially due to COVID-19 infection itself. The current results begin to characterize the spectrum of CVD associated with COVID-19 in patients in Upper Egypt.Registration ID: The ID number of this study is IRB no: 17300470.
Nigral Iron Deposition Is Associated With Levodopa-Induced Dyskinesia in Parkinson’s Disease
Authors: Song Tianbin , Li Jiping , Mei Shanshan , Jia Xiaofei , Yang Hongwei , Ye Yongquan , Yuan Jianmin , Zhang Yuqing , Lu Jie 
Published: March 2021

ObjectiveTo investigate iron deposition in the substantia nigra (SN) of Parkinson’s disease (PD) patients associated with levodopa-induced dyskinesia (LID).MethodsSeventeen PD patients with LID, 17 PD patients without LID, and 16 healthy controls were recruited for this study. The mean QSM values of the whole, left, and right SN were compared among the three groups. A multivariate logistic regression model was constructed to determine the factors associated with increased risk of LID. The receiver operating characteristic curve of the QSM value of SN in discriminating PD with and without LID was evaluated.ResultsThe mean QSM values of the whole and right SN in the PD with LID were higher than those in the PD without LID (∗P = 0.03, ∗P = 0.03). Multivariate logistic regression analysis revealed that the QSM value of whole, left, or right SN was a predictor of the development of LID (∗P = 0.03, ∗P = 0.04, and ∗P = 0.04). The predictive accuracy of LID in adding the QSM value of the whole, left, and right SN to LID-related clinical risk factors was 70.6, 64.7, and 67.6%, respectively. The QSM cutoff values between PD with and without LID of the whole, left, and right SN were 148.3, 165.4, and 152.7 ppb, respectively.ConclusionThis study provides the evidence of higher iron deposition in the SN of PD patients with LID than those without LID, suggesting that the QSM value of the SN may be a potential early diagnostic neuroimaging biomarker for LID.
Regional Variations of Insulin Secretion and Insulin Sensitivity in Japanese Participants With Normal Glucose Tolerance
Authors: Watanabe Kiriko , Higa Moritake , Hasegawa Yoshimasa , Kudo Akihiro , Allsopp Richard C. , Willcox Bradley J. , Willcox Donald C. , Sata Masataka , Masuzaki Hiroaki , Shimabukuro Michio 
Published: March 2021

Purpose: Regional differences in dietary patterns in Asian countries might affect the balance of insulin response and sensitivity. However, this notion is yet to be validated. To clarify the regional differences in the insulin response and sensitivity and their relationship to nutrients, we compared the insulin secretory response during an oral glucose tolerance test in Japanese participants.Methods: This observational retrospective cohort study analyzed the data from participants with normal glucose tolerance (NGT) from four distinct areas of Japan with regard to the food environment: Fukushima, Nagano, Tokushima, and Okinawa based on data available in the Japanese National Health Insurance database.Results: Although the glucose levels were comparable among the four regions, the insulin responses were significantly different among the regions. This difference was observed even within the same BMI category. The plot between the insulin sensitivity index (Matsuda index) and insulinAUC/glucoseAUC or the insulinogenic index showed hyperbolic relationships with variations in regions. The indices of insulin secretion correlated positively with fat intake and negatively with the intake of fish, carbohydrate calories, and dietary fiber.Conclusions: We found that significant regional differences in insulin response and insulin sensitivity in Japanese participants and that nutritional factors may be linked to these differences independently of body size/adiposity. Insulin response and insulin sensitivity can vary among adult individuals, even within the same race and the same country, and are likely affected by environmental/lifestyle factors as well as genetic traits.
Bronchial Washing Fluid Versus Plasma and Bronchoscopy Biopsy Samples for Detecting Epidermal Growth Factor Receptor Mutation Status in Lung Cancer
Authors: Zhang Xinyu , Li Chun , Ye Maosong , Hu Qin , Hu Jie , Gong Ziying , Li Jieyi , Zhao Xiaokai , Xu Yiqing , Zhang Daoyun , Hou Yingyong , Zhang Xin 
Published: March 2021

BackgroundBronchial washing fluid (BWF) is a common specimen collected during bronchoscopy and has been suggested to contain both tumor cells and cell-free DNA. However, there is no consensus on the feasibility of BWF in epidermal growth factor receptor (EGFR) genetic analysis because of the limited sample size and varying results in previous studies. This study compared the feasibility, sensitivity, and specificity of detecting EGFR mutation using BWF, bronchoscopy biopsy, and plasma samples in patients with lung cancer (LC).Materials and MethodsA total of 144 patients (110 with LC and 34 without LC) were enrolled in the study. During diagnostic bronchoscopy for suspected LC lesions, bronchial washing with saline was performed directly or through a guide sheath. BWF was collected as well as paired bronchoscopy biopsy and plasma samples, and EGFR mutation testing was performed via highly sensitive blocker polymerase chain reaction. The EGFR mutation status of histologic samples was set as the standard reference.ResultsCompared with the histologic samples, the sensitivity, specificity, and concordance rate of EGFR mutation detected in BWF samples were 92.5%, 100%, and 97.9%, respectively. Moreover, BWF showed a higher sensitivity in EGFR mutation testing than both plasma (100% [8/8] vs. 62.5% [5/8], p = 0.095) and bronchoscopy biopsy samples (92.5% [37/40] vs. 77.5% [31/40], p = 0.012) and identified EGFR mutations in 6 cases whose biopsy failed to establish an LC diagnosis. The diameter of the target lesion and its contact degree with BWF were positive predictive factors for EGFR testing results.ConclusionsBWF yields a high sensitivity in EGFR mutation testing, having high concordance with histologic samples, and presenting the benefit of rapid EGFR mutation detection in LC patients.
M2 Macrophage Co-Expression Factors Correlate With Immune Phenotype and Predict Prognosis of Bladder Cancer
Authors: Wang Yutao , Yan Kexin , Wang Jianfeng , Lin Jiaxing , Bi Jianbin 
Published: March 2021

PurposeTherapeutic targets of tumor-associated macrophages have been discovered and used clinically as immunotherapy. M2 macrophages are tumor-associated macrophages that promote cancer progression. This article explores the related factors and the effects of type M2 macrophages.MethodWe obtained bladder cancer (BC) sequencing data from TCGA and GSE31189. We used the CIBERSORT algorithm calculate M2 macrophage proportions among 22 type immune cells. The Estimate package was used to measure BC purity. M2 macrophage-related genes were selected using WGCNA. Receiver operating characteristic curves and Kaplan–Meier analyses were performed to determine the risk score, conducted for M2 macrophage-related factors. The Pearson test was used to determine the correlation among M2 macrophage-related genes, clinical phenotype, immune phenotype and tumor mutation burden (TMB). The TIMER database was used to calculate correlations among M2 macrophages and other cancers.ResultsExpression of four M2 macrophages co-expressed genes (CD163, CD209, CSF1, MMD) positively correlated with infiltration of M2 macrophages, which were enriched in the negative regulation of immune system process and the positive regulation of tumor necrosis factor production. M2 macrophage-related factors are robust biomarkers for predicting the BC and immune phenotypes. The Cox regression model built on these four co-expression factors showed a close correlation with outcome (AUC = 0.64). The four co-expression factors negatively correlated outcome and TMB.ConclusionFour co-expressed genes promote high levels of infiltration of type M2 macrophages in the negative regulation of immune system processes and the positive regulation of tumor necrosis factor production processes. These co-expressed genes and the biological process they involve might suggest new strategies for regulation of chemotaxis in M2 macrophages.
Feasibility of Doppler Ultrasound for Cortical Cerebral Blood Flow Velocity Monitoring During Major Non-cardiac Surgery of Newborns
Authors: Costerus Sophie A. , Kortenbout Anna J. , Vos Hendrik J. , Govaert Paul , Tibboel Dick , Wijnen René M. H. , de Jong Nico , Bosch Johan G. , de Graaff Jurgen C. 
Published: March 2021

Background and Aim: Newborns needing major surgical intervention are at risk of brain injury and impaired neurodevelopment later in life. Disturbance of cerebral perfusion might be an underlying factor. This study investigates the feasibility of serial transfontanellar ultrasound measurements of the pial arteries during neonatal surgery, and whether perioperative changes in cerebral perfusion can be observed and related to changes in the perioperative management.Methods: In this prospective, observational feasibility study, neonates with congenital diaphragmatic hernia and esophageal atresia scheduled for surgical treatment within the first 28 days of life were eligible for inclusion. We performed transfontanellar directional power Doppler and pulsed wave Doppler ultrasound during major high-risk non-cardiac neonatal surgery. Pial arteries were of interest for the measurements. Extracted Doppler ultrasound parameters were: peak systolic velocity, end diastolic velocity, the resistivity index and pulsatility index.Results: In 10 out of 14 patients it was possible to perform perioperative measurements; the others failed for logistic and technical reasons. In 6 out of 10 patients, it was feasible to perform serial intraoperative transfontanellar ultrasound measurements with directional power Doppler and pulsed wave Doppler of the same pial artery during neonatal surgery. Median peak systolic velocity was ranging between 5.7 and 7.0 cm s−1 and end diastolic velocity between 1.9 and 3.2 cm s−1. In patients with a vasoactive-inotropic score below 12 the trend of peak systolic velocity and end diastolic velocity corresponded with the mean arterial blood pressure trend.Conclusion: Perioperative transfontanellar ultrasound Doppler measurements of the pial arteries are feasible and provide new longitudinal data about perioperative cortical cerebral blood flow velocity.Trial Registration:https://www.trialregister.nl/trial/6972, identifier: NL6972.