bluuebunny/crossref_metadata_2025_split huggingface dataset:
Anti-Carbamylated LL37 Antibodies Promote Pathogenic Bone Resorption in Rheumatoid Arthritis
Authors: O’Neil Liam J. , Oliveira Christopher B. , Sandoval-Heglund Donavon , Barrera-Vargas Ana , Merayo-Chalico Javier , Aguirre-Aguilar Eduardo , Kaplan Mariana J. , Carmona-Rivera Carmelo 
Published: September 2021

ObjectiveAntibodies against carbamylated proteins (anti-CarP) are associated with poor prognosis and the development of bone erosions in rheumatoid arthritis (RA). RA neutrophils externalize modified autoantigens through the formation of neutrophil extracellular traps (NETs). Increased levels of the cathelicidin LL37 have been documented in the synovium of RA patients, but the cellular source remains unclear. We sought to determine if post-translational modifications of LL37, specifically carbamylation, occur during NET formation, enhance this protein’s autoantigenicity, and contribute to drive bone erosion in the synovial joint.MethodsELISA and Western blot analyses were used to identify carbamylated LL37 (carLL37) in biological samples. Anti-carLL37 antibodies were measured in the serum of HLA-DRB1*04:01 transgenic mice and in human RA synovial fluid.ResultsElevated levels of carLL37 were found in plasma and synovial fluid from RA patients, compared to healthy controls. RA NETs release carLL37 and fibroblast-like synoviocytes (FLS) internalized NET-bound carLL37 and loaded it into their MHCII compartment. HLA-DRB1*04:01 transgenic mice immunized with FLS containing NETs developed autoantibodies against carLL37. Anti-carLL37 antibodies were present in RA sera and synovial fluid and they correlated with radiologic bone erosion scores of the hands and feet in RA patients. CarLL37-IgG immune complexes enhanced the ability of monocytes to differentiate into osteoclasts and potentiated osteoclast-mediated extracellular matrix resorption.ConclusionsNETs are a source of carLL37 leading to induction of anti-carbamylated autoantibody responses. Furthermore, carLL37-IgG immune complexes may be implicated in the bone damage characteristic of RA. These results support that dysregulated NET formation has pathogenic roles in RA.
Use of Outpatient-Derived COVID-19 Convalescent Plasma in COVID-19 Patients Before Seroconversion
Authors: Wirz Oliver F. , Röltgen Katharina , Stevens Bryan A. , Pandey Suchitra , Sahoo Malaya K. , Tolentino Lorna , Verghese Michelle , Nguyen Khoa , Hunter Molly , Snow Theo Thomas , Singh Abhay Raj , Blish Catherine A. , Cochran Jennifer R. , Zehnder James L. , Nadeau Kari C. , Pinsky Benjamin A. , Pham Tho D. , Boyd Scott D. 
Published: September 2021

BackgroundTransfusion of COVID-19 convalescent plasma (CCP) containing high titers of anti-SARS-CoV-2 antibodies serves as therapy for COVID-19 patients. Transfusions early during disease course was found to be beneficial. Lessons from the SARS-CoV-2 pandemic could inform early responses to future pandemics and may continue to be relevant in lower resource settings. We sought to identify factors correlating to high antibody titers in convalescent plasma donors and understand the magnitude and pharmacokinetic time course of both transfused antibody titers and the endogenous antibody titers in transfused recipients.MethodsPlasma samples were collected up to 174 days after convalescence from 93 CCP donors with mild disease, and from 16 COVID-19 patients before and after transfusion. Using ELISA, anti-SARS-CoV-2 Spike RBD, S1, and N-protein antibodies, as well as capacity of antibodies to block ACE2 from binding to RBD was measured in an in vitro assay. As an estimate for viral load, viral RNA and N-protein plasma levels were assessed in COVID-19 patients.ResultsAnti-SARS-CoV-2 antibody levels and RBD-ACE2 blocking capacity were highest within the first 60 days after symptom resolution and markedly decreased after 120 days. Highest antibody titers were found in CCP donors that experienced fever. Effect of transfused CCP was detectable in COVID-19 patients who received high-titer CCP and had not seroconverted at the time of transfusion. Decrease in viral RNA was seen in two of these patients.ConclusionOur results suggest that high titer CCP should be collected within 60 days after recovery from donors with past fever. The much lower titers conferred by transfused antibodies compared to endogenous production in the patient underscore the importance of providing CCP prior to endogenous seroconversion.
Predictors of Early Neurological Deterioration in Stroke Due to Vertebrobasilar Occlusion
Authors: Koh Seungyon , Lee Sung Eun , Jung Woo Sang , Choi Jin Wook , Lee Jin Soo , Hong Ji Man , Lee Seong-Joon 
Published: September 2021

Background and Aims: This study explores the predictors of early neurological deterioration (END) in patients with vertebrobasilar occlusion (VBO) in both primary endovascular therapy (EVT) and medical management (MM) groups.Methods: Patients diagnosed with VBO from 2010 to 2018 were included. Comparative and multivariate analyses were used to identify predictors of all-cause END in the EVT group, and END due to ischemia progression (END-IP) in the MM group.Results: In 174 patients with VBO, 43 had END. In the primary EVT group (N = 66), 17 all-cause END occurred. Distal basilar occlusion (odds ratio (OR), 14.5 [95% confidence interval (CI), 1.4–154.4]) and reperfusion failure (eTICI &lt; 2b67 (OR, 5.0 [95% CI, 1.3–19.9]) were predictive of END in multivariable analysis. In the MM group (N=108), 17 END-IP occurred. Higher systolic blood pressure (SBP) at presentation (per 10 mmHg increase, OR, 1.5 [95% CI, 1.1–2.0]), stroke onset-to-door time &lt;24 h (OR, 5.3 [95% CI, 1.1–2.0]), near-total occlusions (OR, 4.9 [95% CI, 1.2–19.6]), lower posterior circulation-Alberta Stroke Program Early CT scores (OR, 1.6 [95% CI, 1.0–2.5]), and lower BATMAN collateral scores (OR, 1.6 [95% CI, 1.1–2.2]) were predictive of END-IP.Conclusions: In patients with stroke due to VBO, potential predictors of END can be identified. In the primary EVT group, failure to achieve reperfusion and distal basilar occlusion were associated with all-cause END. In the MM group, higher SBP at presentation, onset-to-door time less than 24 h, incomplete occlusions, larger infarct cores, and poorer collaterals were associated with END-IP.
Alterations in Sensorimotor and Mesiotemporal Cortices and Diffuse White Matter Changes in Primary Progressive Multiple Sclerosis Detected by Adiabatic Relaxometry
Authors: Filip Pavel , Dufek Michal , Mangia Silvia , Michaeli Shalom , Bareš Martin , Schwarz Daniel , Rektor Ivan , Vojtíšek Lubomír 
Published: September 2021

Background: The research of primary progressive multiple sclerosis (PPMS) has not been able to capitalize on recent progresses in advanced magnetic resonance imaging (MRI) protocols.Objective: The presented cross-sectional study evaluated the utility of four different MRI relaxation metrics and diffusion-weighted imaging in PPMS.Methods: Conventional free precession T1 and T2, and rotating frame adiabatic T1ρ and T2ρ in combination with diffusion-weighted parameters were acquired in 13 PPMS patients and 13 age- and sex-matched controls.Results: T1ρ, a marker of crucial relevance for PPMS due to its sensitivity to neuronal loss, revealed large-scale changes in mesiotemporal structures, the sensorimotor cortex, and the cingulate, in combination with diffuse alterations in the white matter and cerebellum. T2ρ, particularly sensitive to local tissue background gradients and thus an indicator of iron accumulation, concurred with similar topography of damage, but of lower extent. Moreover, these adiabatic protocols outperformed both conventional T1 and T2 maps and diffusion tensor/kurtosis approaches, methods previously used in the MRI research of PPMS.Conclusion: This study introduces adiabatic T1ρ and T2ρ as elegant markers confirming large-scale cortical gray matter, cerebellar, and white matter alterations in PPMS invisible to other in vivo biomarkers.
Free-Living Energy Balance Behaviors Are Associated With Greater Weight Loss During a Weight Loss Program
Authors: Myers Anna , Camidge Diana , Croden Fiona , Gibbons Catherine , Stubbs R. James , Blundell John , Finlayson Graham , Buckland Nicola 
Published: September 2021

Introduction: Free-living movement (physical activity [PA] and sedentary behavior [SB]) and eating behaviors (energy intake [EI] and food choice) affect energy balance and therefore have the potential to influence weight loss (WL). This study explored whether free-living movement and/or eating behaviors measured early (week 3) in a 14-week WL programme or their change during the intervention are associated with WL in women.Methods: In the study, 80 women (M ± SD age: 42.0 ± 12.4 years) with overweight or obesity [body mass index (BMI): 34.08 ± 3.62 kg/m2] completed a 14 week WL program focused primarily on diet (commercial or self-led). Body mass (BM) was measured at baseline, and again during week 2 and 14 along with body composition. Free-living movement (SenseWear Armband) and eating behavior (weighed food diaries) were measured for 1 week during week 3 and 12. Hierarchical multiple regression analyses examined whether early and early-late change in free-living movement and eating behavior were associated with WL. The differences in behavior between clinically significant weight losers (CWL; ≥5% WL) and non-clinically significant weight losers (NWL; ≤ 3% WL) were compared.Results: The energy density of food consumed [β = 0.45, p &lt; 0.001] and vigorous PA [β = −0.30, p &lt; 0.001] early in the intervention (regression model 1) and early-late change in light PA [β = −0.81 p &lt; 0.001], moderate PA [β = −1.17 p &lt; 0.001], vigorous PA [β = −0.49, p &lt; 0.001], total energy expenditure (EE) [β = 1.84, p &lt; 0.001], and energy density of food consumed [β = 0.27, p = 0.01] (regression model 2) significantly predicted percentage change in BM. Early in the intervention, CWL consumed less energy dense foods than NWL [p = 0.03]. CWL showed a small but significant increase in vigorous PA, whereas NWL showed a slight decrease in PA [p = 0.04].Conclusion: Both early and early-late change in free-living movement and eating behaviors during a 14 week WL program are predictors of WL. These findings demonstrate that specific behaviors that contribute to greater EE (e.g., vigorous PA) and lower EI (e.g., less energy-dense foods) are related to greater WL outcomes. Interventions targeting these behaviors can be expected to increase the effectiveness of WL programs.
Circulating Tumor Cells in Desmoid Tumors: New Perspectives
Authors: Braun Alexcia C. , Campos Fernando A. B. , Abdallah Emne A. , Ruano Anna P. C. , Medina Tiago da S. , Tariki Milena S. , Pinto Fabio F. E. , de Mello Celso A. L. , Chinen Ludmilla T. D. 
Published: September 2021

IntroductionDesmoid tumor (DT) is a rare neoplasm with high local recurrence rates, composed of fibroblastic cells that are characterized by the expression of key molecules, including the intermediate filament vimentin, cyclooxygenase-2 (COX-2), and nuclear β-catenin, and lack of epithelial markers. Circulating tumor cells (CTCs) isolated from the peripheral blood of patients with sarcomas and other neoplasms can be used as early biomarkers of tumor invasion and dissemination. Moreover, CTCs can also re-colonize their tumors of origin through a process of “tumor self-seeding.”ObjectivesWe aimed to identify CTCs in the peripheral blood of patients with DT and evaluate their expression of β-catenin, transforming growth factor receptor I (TGF-βRI), COX-2, and vimentin proteins.Material and MethodsWe conducted a prospective study of patients with initial diagnosis or relapsed DT with measurable disease. Blood samples from each patient were processed and filtered by ISET® (Rarecells, France) for CTC isolation and quantification. The CTC expression of β-catenin, COX-2, TGF-βRI, and vimentin was analyzed by immunocytochemistry (ICC).ResultsA total of 18 patients were included, and all had detectable CTCs. We found a concordance of β-catenin expression in both CTCs and primary tumors in 42.8% (6/14) of cases by using ICC and immunohistochemistry, respectively.ConclusionsOur study identified a high prevalence of CTCs in DT patients. Concordance of β-catenin expression between primary tumor and CTCs brings new perspectives to assess the dynamics of CTCs in the blood compartment, opening new avenues for studying the biology and behavior of DT. In addition, these results open the possibility of using CTCs to predict DT dynamics at the time of disease progression and treatment. Further studies with larger sample sizes are needed to validate our findings.
Addition of Induction or Consolidation Chemotherapy in Definitive Concurrent Chemoradiotherapy Versus Concurrent Chemoradiotherapy Alone for Patients With Unresectable Esophageal Cancer: A Systematic Review and Meta-Analysis
Authors: Wang Jianing , Xiao Linlin , Wang Shuai , Pang Qingsong , Wang Jun 
Published: September 2021

BackgroundConcurrent chemoradiotherapy (CCRT) has become the standard of care in esophageal carcinoma patients who are not surgical candidates. The efficacy of induction chemotherapy (IC) or consolidation chemotherapy (CCT) for unresectable esophageal cancer (EC) treated with CCRT is unclear. We performed a systematic review and meta-analysis of published papers to evaluate the potential benefit of IC or CCT for patients with EC.MethodsEligible studies of IC followed by CCRT (IC-CCRT) vs. CCRT alone or CCRT followed by CCT (CCRT-CCT) vs. CCRT alone were retrieved through extensive searches of the PubMed, Science Direct, Embase, and Cochrane Library databases from the establishment of the database to July 31, 2021. Data such as 1-, 2-, 3-, and 5-year overall survival (OS), local recurrence rate (LRR), and distant metastasis rate (DMR) were collected for meta-analysis to evaluate the efficacy of IC/CCT.ResultsFour studies of IC-CCRT vs. CCRT including 836 EC patients and six studies of CCRT-CCT vs. CCRT including 1,339 patients with esophageal squamous cell carcinoma (ESCC) were finally identified in our analysis. Both IC-CCRT group [hazard ratio (HR) 0.446, 95% CI 0.286–0.693; p &lt; 0.001] and CCRT-CCT group (HR 0.542, 95% CI 0.410–0.716; p &lt; 0.001) exhibited statistically significant improvement in 1-year OS rate compared to that of CCRT, while the 2-year OS rate of IC-CCRT (HR 0.803, 95% CI 0.589–1.095; p = 0.166) or CCRT-CCT (HR 0.783, 95% CI 0.600–1.022; p = 0.072) was similar with that of CCRT. And the 3-year OS rate between IC-CCRT and CCRT was similar (HR 1.065, 95% CI 0.789–1.439; p = 0.680). However, comparing with CCRT alone, the CCRT-CCT group had lower DMR [odds ratio (OR) 1.562, 95% CI 1.090–2.240; p = 0.015] and higher 3-year OS rate (HR 0.786, 95% CI 0.625–0.987; p = 0.039). Besides, no differences were observed between the CCRT-CCT and CCRT groups in 5-year OS rate (HR 0.923, 95% CI 0.706–1.205; p = 0.555) and LRR (OR 0.899, 95% CI 0.686–1.179; p = 0.441).ConclusionThe study revealed the short-time survival benefit of additional IC or CCT compared to CCRT alone for patients with unresectable EC, and CCRT followed by CCT could significantly reduce the risk of distant metastases.
CT Radiomics for the Preoperative Prediction of Ki67 Index in Gastrointestinal Stromal Tumors: A Multi-Center Study
Authors: Zhao Yilei , Feng Meibao , Wang Minhong , Zhang Liang , Li Meirong , Huang Chencui 
Published: September 2021

PurposeThis study established and verified a radiomics model for the preoperative prediction of the Ki67 index of gastrointestinal stromal tumors (GISTs).Materials and MethodsA total of 344 patients with GISTs from three hospitals were divided into a training set and an external validation set. The tumor region of interest was delineated based on enhanced computed-tomography (CT) images to extract radiomic features. The Boruta algorithm was used for dimensionality reduction of the features, and the random forest algorithm was used to construct the model for radiomics prediction of the Ki67 index. The receiver operating characteristic (ROC) curve was used to evaluate the model’s performance and generalization ability.ResultsAfter dimensionality reduction, a feature subset having 21 radiomics features was generated. The generated radiomics model had an the area under curve (AUC) value of 0.835 (95% confidence interval(CI): 0.761–0.908) in the training set and 0.784 (95% CI: 0.691–0.874) in the external validation cohort.ConclusionThe radiomics model of this study had the potential to predict the Ki67 index of GISTs preoperatively.
Analysis of EPID Transmission Fluence Maps Using Machine Learning Models and CNN for Identifying Position Errors in the Treatment of GO Patients
Authors: Dai Guyu , Zhang Xiangbin , Liu Wenjie , Li Zhibin , Wang Guangyu , Liu Yaxin , Xiao Qing , Duan Lian , Li Jing , Song Xinyu , Li Guangjun , Bai Sen 
Published: September 2021

PurposeTo find a suitable method for analyzing electronic portal imaging device (EPID) transmission fluence maps for the identification of position errors in the in vivo dose monitoring of patients with Graves’ ophthalmopathy (GO).MethodsPosition errors combining 0-, 2-, and 4-mm errors in the left-right (LR), anterior-posterior (AP), and superior-inferior (SI) directions in the delivery of 40 GO patient radiotherapy plans to a human head phantom were simulated and EPID transmission fluence maps were acquired. Dose difference (DD) and structural similarity (SSIM) maps were calculated to quantify changes in the fluence maps. Three types of machine learning (ML) models that utilize radiomics features of the DD maps (ML 1 models), features of the SSIM maps (ML 2 models), and features of both DD and SSIM maps (ML 3 models) as inputs were used to perform three types of position error classification, namely a binary classification of the isocenter error (type 1), three binary classifications of LR, SI, and AP direction errors (type 2), and an eight-element classification of the combined LR, SI, and AP direction errors (type 3). Convolutional neural network (CNN) was also used to classify position errors using the DD and SSIM maps as input.ResultsThe best-performing ML 1 model was XGBoost, which achieved accuracies of 0.889, 0.755, 0.778, 0.833, and 0.532 in the type 1, type 2-LR, type 2-AP, type 2-SI, and type 3 classification, respectively. The best ML 2 model was XGBoost, which achieved accuracies of 0.856, 0.731, 0.736, 0.949, and 0.491, respectively. The best ML 3 model was linear discriminant classifier (LDC), which achieved accuracies of 0.903, 0.792, 0.870, 0.931, and 0.671, respectively. The CNN achieved classification accuracies of 0.925, 0.833, 0.875, 0.949, and 0.689, respectively.ConclusionML models and CNN using combined DD and SSIM maps can analyze EPID transmission fluence maps to identify position errors in the treatment of GO patients. Further studies with large sample sizes are needed to improve the accuracy of CNN.
Erythropoietin Produces a Dual Effect on Carotid Body Chemoreception in Male Rats
Authors: Arias-Reyes Christian , Laouafa Sofien , Zubieta-DeUrioste Natalia , Joseph Vincent , Bairam Aida , Schneider Gasser Edith M. , Soliz Jorge 
Published: September 2021

Erythropoietin (EPO) regulates respiration under conditions of normoxia and hypoxia through interaction with the respiratory centers of the brainstem. Here we investigate the dose-dependent impact of EPO in the CB response to hypoxia and hypercapnia. We show, in isolated “en bloc” carotid body (CB) preparations containing the carotid sinus nerve (CSN) from adult male Sprague Dawley rats, that EPO acts as a stimulator of CSN activity in response to hypoxia at concentrations below 0.5 IU/ml. Under hypercapnic conditions, EPO did not influence the CSN response. EPO concentrations above 0.5 IU/ml decreased the response of the CSN to both hypoxia and hypercapnia, reaching complete inhibition at 2 IU/ml. The inhibitory action of high-dose EPO on the CSN activity might result from an increase in nitric oxide (NO) production. Accordingly, CB preparations were incubated with 2 IU/ml EPO and the unspecific NO synthase inhibitor (L-NAME), or the neuronal-specific NO synthase inhibitor (7NI). Both NO inhibitors fully restored the CSN activity in response to hypoxia and hypercapnia in presence of EPO. Our results show that EPO activates the CB response to hypoxia when its concentration does not exceed the threshold at which NO inhibitors masks EPO’s action.
Effects of Corticosteroid Treatment on Mycophenolic Acid Exposure in Renal Transplant Patients—Results From the SAILOR Study
Authors: Nourbakhsh Nima , Ekberg Jana , Skov Karin , Peters Christian Daugaard , Øzbay Aygen , Lindner Per , Buus Niels Henrik 
Published: September 2021

Background: Mycophenolic acid (MPA) is a potent immunosuppressive agent used in solid organ transplantation. MPA exhibits large interindividual variation in dose-normalized plasma concentrations but is nevertheless usually prescribed as a fixed dose without use of therapeutic drug monitoring (TDM). Data on the effect of corticosteroid (CS) treatment on MPA concentrations during concomitant tacrolimus treatment remains sparse.Methods: Data is based on TDM of MPA area under the concentration curve (AUC) in 210 renal transplant recipients participating in the prospective, randomized, controlled, multi-center trial (SAILOR) where a steroid-free immunosuppressive regimen with mycophenolate mofetil (MMF) and low-dose tacrolimus was compared with a conventional prednisolone-based treatment regimen. Multilevel mixed-effects linear regression post-hoc analyses of MPA AUC was performed.Results: Median MPA AUC at baseline (within the first 2 weeks post-transplant) in patients taking 2 g MMF daily was 53 mg*h/L (interquartile range: 43–69 mg*h/L, min: 24—max: 117 mg*h/L). Between-patient variation in MPA AUC was up to 5-fold on the same MMF dose. Patients in the steroid-free group had 12.5% lower (95% CI; 3.2–20.9%, p = 0.01) MPA AUC levels at baseline compared to the steroid treated group. During follow-up (14 days–2 years post-transplant) there were no significant differences in MPA AUC between the groups with MPA AUC being 4.2% lower (95% CI: −4.8%−12,5%, p = 0.35) in the steroid-free vs standard treatment group in restricted analysis after multivariate adjustment for tacrolimus trough level, body weight, time after transplantation and MMF dose. MMF dose was positively correlated with MPA AUC (p &lt; 0.001) whereas body weight was negatively correlated with MPA AUC (p &lt; 0.001). MPA AUC was 0.4% (95% CI: 0.2–0.6%, p &lt; 0.001) lower per 1 kg increase in weight. Tacrolimus trough levels had no significant effect on MPA AUC.Conclusion: Immunosuppression with CS during concomitant tacrolimus treatment was shortly after transplantation associated with a significantly higher MPA exposure but the effect was small and not maintained during follow-up. Low body weight was associated with higher MPA exposure, which suggests a potential for weight adjusted MMF dosing.