bluuebunny/crossref_metadata_2025_split huggingface dataset:
Correlation analysis of carotid plaque in young patients with newly diagnosed type 2 diabetes and platelet-to-lymphocyte ratio and neutrophil–lymphocyte ratio
Authors: Wen Huijun , Yu Hai 
Published: January 2022

Objective Platelet-to-lymphocyte ratio (PLR) and neutrophil–lymphocyte ratio (NLR) have been reported to be related to atherosclerosis. The relationship between PLR, NLR, and carotid atherosclerotic plaque in young patients with newly diagnosed type 2 diabetes has not been clinically reported. This study aimed to analyze the relationship between PLR, NLR, and carotid plaques in young patients with newly diagnosed type 2 diabetes. Method The total 268 patients were divided into the intima-media–thickening (IMT) group (116 cases) and plaque group (152 cases). The plaque group was divided into grade I (62 cases), grade II (47 cases), and grade III groups (43 cases). The counts of platelets, neutrophils, and lymphocytes were determined. Results The diagnostic effect of PLR and NLR was evaluated by the receiver-operating characteristic curve (ROC) and areas under the curve (AUC). The PLR and NLR values in the observation group were higher than those in the control group; these two values in the plaque group were also higher than those in the IMT group. The two values in the grade III plaque group were higher than those in grade II. The values in the grade II plaque group were also higher than those in the grade I plaque group. The ROC of PLR and NLR were 0.722 and 0.653, and the AUC of PLR and NLR were 111.086 and 2.240. PLR yielded a sensitivity of 0.789 and a specificity of 0.612. Neutrophil–lymphocyte ratio yielded a sensitivity of 0.809 and a specificity of 0.511. Conclusion The PLR and NLR may be related to carotid inflammation in patients and positively correlated with carotid plaque.
Thrombectomy in basilar artery occlusion
Authors: Sommer Peter , Scharer Sebastian , Posekany Alexandra , Serles Wolfgang , Marko Martha , Langer Agnes , Fertl Elisabeth , Sykora Marek , Lang Wilfried , Dafert Sebastian , Seiringer Fiona , Kiechl Stefan , Knoflach Michael , Greisenegger Stefan 
Published: January 2022

Background and Purpose: The benefit of thrombectomy (TE) for acute ischemic stroke (AIS) in patients suffering basilar artery occlusion (BAO) is still unclear. Our aim was to analyze functional outcome after 3 months in BAO compared to anterior circulation large vessel occlusion (ACLVO) in a nationwide registry. Methods: Patients enrolled into the Austrian Endostroke Registry from 2013 to 2018 were analyzed. We used propensity score matching to control for imbalances and to compare patients with BAO and ACLVO. The primary outcome was favorable functional outcome after 3 months measured by the modified Rankin Scale (mRS) (0–2). Multivariate models were applied to estimate the effect of localization (BAO vs ACLVO). Results: In total, 2288 patients underwent TE for AIS with proximal vessel occlusion, of these 267 with BAO. Two hundred and sixty-four patients with BAO were matched to 264 patients with ACLVO. Baseline characteristics were well-balanced. The 90-day mortality did not significantly differ between patients with BAO and ACLVO. In a multivariate logistic regression model, we did not detect a significant difference in functional outcome between BAO and ACLVO (odds ratio for favorable outcome defined as mRS = 0–2: 1.19; 95% confidence interval (CI) = 0.78–1.81; p = 0.42). In patients with an onset-to-door-time ⩾270 min, TE of BAO was associated with poor functional outcome defined as mRS 3–6 (odds ratio (OR) = 3.97; 95% CI = 1.32–11.94; p = 0.01) as compared to ACLVO. Conclusion: In this study, functional outcome did not differ after TE in patients with BAO and ACLVO overall; however, we detected an association of BAO with poor outcome in patients arriving late.
Beyond Distance: A Simple Qualitative Assessment of the Single-Leg Hop Test in Return-to-Play Testing
Authors: Di Paolo Stefano , Zaffagnini Stefano , Tosarelli Filippo , Grassi Alberto , Della Villa Francesco 
Published: January 2022

Background: Limb symmetry index in the single-leg hop (SLH) test has been questioned for its low predictive value in identifying secondary anterior cruciate ligament (ACL) injury. The purpose of this study was to describe a qualitative 2-dimensional (2D) scoring system for the assessment of the SLH test and associate it with the vertical ground-reaction forces (vGRF) and sagittal plane biomechanics evaluated through gold standard 3D motion analysis. Hypothesis: Stiff landings would be associated with low 2D scores. Study Design: Descriptive laboratory study. Level of Evidence: Level 4. Methods: Thirty-four competitive football (soccer) players (age 22.8 ± 4.1 years, 16 women) were enrolled. Each athlete performed a series of SLH tests. Three-dimensional motion analysis was recorded using 10 stereophotogrammetric cameras, a force platform, and 3 high-speed cameras. The 2D qualitative assessment was performed through a scoring system based on the video-analysis of sagittal plane joint kinematics. A score of 0/2 (inadequate), 1/2 (partially adequate), or 2/2 (adequate) was attributed to the movement, based on objective measurements. The vGRF was extracted from the force platform and grouped according to the results of the 2D evaluation. Results: Significantly higher vGRF (stiffer landing) was found for athletes obtaining a 0/2 score compared with those obtaining a 2/2 score (up to 0.8 body weight higher, P < 0.01). A significant negative rank correlation was found between the vGRF and the total score (ρ = −0.17, P = 0.03). Conclusion: The qualitative scoring system effectively identified stiff landings in the SLH for distance test. Clinical Relevance: The qualitative scoring system could be a user-friendly standardized method to assess athletes’ movement quality in return to sport clearance decision after ACL injury.
Clinical features of eczema and dermatitis in the elderly: A cross-sectional study in mainland China
Authors: Wang Xin , Li Lin-Feng 
Published: January 2022

Purpose: The clinical features of eczema and dermatitis in the elderly have not been fully studied. To investigate the proportion and clinical features of geriatric eczema patients in mainland China. Patients and methods: A multicenter cross-sectional study conducted in outpatients with eczema from 39 tertiary hospitals in 15 provinces. Results: 1128 elderly patients (12.88%) had eczema and dermatitis. The mean age of those was 68.2 ± 6.8 years (range, 60–90 years) with a median course of 5.5 ± 8.9 years, which is much longer than that of non-geriatric patients (2.6 ± 4.1 years, p < 0.001). Compared to non-geriatric patients, more patients involved in extremities (76.2% vs 61.5%, p < 0.001) and trunk (37.2% vs 26.4%, p < 0.001), but less in head and neck (18.3% vs 30.4%, p < 0.001; 25.3% vs 20.6%, p < 0.001). 13.4% of eczema and dermatitis in the elderly was widespread, which is much higher than that of 8% in non-geriatric group (13.4% vs 8%, p < 0.001). 22.9% of geriatric eczema patients reported severe itching, which is much higher than that of 14% in counterparts (22.9% vs 14%, p < 0.001). A positive correlation was observed between age and severe itching (Spearman’s rank correlation test, p < 0.001). More geriatric patients had xerosis (39.6% vs 30.4%, p < 0.001) and more lichenification was found (25.6% vs 13.3%, p < 0.001). Conclusion: More than 10% of eczema occurs in the elderly patients. Longer disease duration, more severe itching, more extremities and trunk involvement, and prone to widespread, xerosis, and lichenification make it a special entity which should be studied further.
Early Weight Bearing after Distal Femur Fracture Fixation
Authors: Striano Brendan M. , Grisdela Phillip T. , Shapira Shay , Heng Marilyn 
Published: January 2022

Objectives To assess outcomes following early weight bearing after distal femur fracture fixation with locked lateral plating. Design Retrospective cohort study Setting Two Level 1 Academic Trauma Centers. Patients/Participants Patients 18 years and older with distal femur fractures treated with locked lateral plating Intervention Early full weight bearing (defined as less than 30 days from date of surgery) versus restricted post-operative weight bearing Main Outcome Measurements Composite complication comprising malunion, nonunion, surgical site infection, re-admission, or death Results 270 distal femur fractures were reviewed, with 165 meeting inclusion criteria. 21 patients had been allowed early full weight bearing. Fractures were divided into two groups based on when full weight bearing was allowed post-operatively. The two groups had similar fractures as determined by the distribution of AO distal femur fracture and Su periprosthetic femur fracture classifications. The early weight bearing group was significantly older and more comorbid. Despite being older, more comorbid, and allowed early full weight bearing on their fracture fixation construct, there was no difference in the rate of composite complications between groups. Conclusion Our data contributes to the small, but growing body of literature that has found no increased rate of fracture related complications in surgically treated distal femur fractures allowed early post-operative weight bearing. Level of Evidence Therapeutic Level III Study.
Charting the past and possible futures of planning support systems: Results of a citation network analysis
Authors: Daniel Claire , Pettit Christopher 
Published: January 2022

Recent years have seen a renewed interest in the possibilities of digital technology to assist with urban planning, spurred by increased digitisation of planning work, and ever improving data availability and processing capabilities. Hidden behind recent developments is over 30 years of research and development by scholars in the field of Planning Support Systems (PSS), although to date there have been few attempts to systematically characterise their output or achievements. This paper reports on the results of a citation network analysis (CNA) on the PSS literature contained within the Scopus database, a systematic method to describe the overall structure of the field, mapping out of key research streams and how they change over time. The analysis reveals 27 distinct research streams under four themes, split between technical and applied research. There is strong evidence of a field still clearly defined by its roots in comprehensive software systems used for scenario and land use planning although shifting over time from a focus on the development of modelling techniques to applied research and case studies in the use of applications. Research output has remained steady in the context of exponential growth in related literature including smart cities, urban science and urban analytics. These findings support calls for a refreshed approach to the field as planning support science and the map produced by this analysis provides a valuable framework to navigate past research efforts to inform a new era of digital planning efforts.
PI3Kδ/γ inhibition promotes human CART cell epigenetic and metabolic reprogramming to enhance antitumor cytotoxicity
Authors: Funk Christopher Ronald , Wang Shuhua , Chen Kevin Z. , Waller Alexandra , Sharma Aditi , Edgar Claudia L. , Gupta Vikas A. , Chandrakasan Shanmuganathan , Zoine Jaquelyn T. , Fedanov Andrew , Raikar Sunil S. , Koff Jean L. , Flowers Christopher R. , Coma Silvia , Pachter Jonathan A. , Ravindranathan Sruthi , Spencer H. Trent , Shanmugam Mala , Waller Edmund K. 
Published: January 2022

AbstractCurrent limitations in using chimeric antigen receptor T(CART) cells to treat patients with hematological cancers include limited expansion and persistence in vivo that contribute to cancer relapse. Patients with chronic lymphocytic leukemia (CLL) have terminally differentiated T cells with an exhausted phenotype and experience low complete response rates after autologous CART therapy. Because PI3K inhibitor therapy is associated with the development of T-cell–mediated autoimmunity, we studied the effects of inhibiting the PI3Kδ and PI3Kγ isoforms during the manufacture of CART cells prepared from patients with CLL. Dual PI3Kδ/γ inhibition normalized CD4/CD8 ratios and maximized the number of CD8+ T-stem cell memory, naive, and central memory T-cells with dose-dependent decreases in expression of the TIM-3 exhaustion marker. CART cells manufactured with duvelisib (Duv-CART cells) showed significantly increased in vitro cytotoxicity against CD19+ CLL targets caused by increased frequencies of CD8+ CART cells. Duv-CART cells had increased expression of the mitochondrial fusion protein MFN2, with an associated increase in the relative content of mitochondria. Duv-CART cells exhibited increased SIRT1 and TCF1/7 expression, which correlated with epigenetic reprograming of Duv-CART cells toward stem-like properties. After transfer to NOG mice engrafted with a human CLL cell line, Duv-CART cells expressing either a CD28 or 41BB costimulatory domain demonstrated significantly increased in vivo expansion of CD8+ CART cells, faster elimination of CLL, and longer persistence. Duv-CART cells significantly enhanced survival of CLL-bearing mice compared with conventionally manufactured CART cells. In summary, exposure of CART to a PI3Kδ/γ inhibitor during manufacturing enriched the CART product for CD8+ CART cells with stem-like qualities and enhanced efficacy in eliminating CLL in vivo.
IRF8 is a transcriptional activator of CD37 expression in diffuse large B-cell lymphoma
Authors: Elfrink Suraya , ter Beest Martin , Janssen Luuk , Baltissen Marijke P. , Jansen Pascal W. T. C. , Kenyon Angelique N. , Steen Raymond M. , de Windt Daynelys , Hagemann Philipp M. , Hess Corine , van Spronsen Dick-Johan , Hoevenaars Brigiet , van der Spek Ellen , Xu-Monette Zijun Y. , Young Ken H. , Kaffa Charlotte , Bervoets Sander , van Heek Jolien , Hesius Eva , de Winde Charlotte M. , Vermeulen Michiel , van den Brand Michiel , Scheijen Blanca , van Spriel Annemiek B. 
Published: January 2022

Abstract
Diffuse large B-cell lymphoma (DLBCL) represents the most common form of non-Hodgkin lymphoma (NHL) that is still incurable in a large fraction of patients. Tetraspanin CD37 is highly expressed on mature B lymphocytes, and multiple CD37-targeting therapies are under clinical development for NHL. However, CD37 expression is nondetectable in ∼50% of DLBCL patients, which correlates with inferior treatment outcome, but the underlying mechanisms for differential CD37 expression in DLBCL are still unknown. Here, we investigated the regulation of the CD37 gene in human DLBCL at the (epi-)genetic and transcriptional level. No differences were observed in DNA methylation within the CD37 promoter region between CD37-positive and CD37-negative primary DLBCL patient samples. On the contrary, CD37-negative DLBCL cells specifically lacked CD37 promoter activity, suggesting differential regulation of CD37 gene expression. Using an unbiased quantitative proteomic approach, we identified transcription factor IRF8 to be significantly higher expressed in nuclear extracts of CD37-positive as compared with CD37-negative DLBCL. Direct binding of IRF8 to the CD37 promoter region was confirmed by DNA pulldown assay combined with mass spectrometry and targeted chromatin immunoprecipitation (ChIP). Functional analysis indicated that IRF8 overexpression enhanced CD37 protein expression, while CRISPR/Cas9 knockout of IRF8 decreased CD37 levels in DLBCL cell lines. Immunohistochemical analysis in a large cohort of primary DLBCL (n = 206) revealed a significant correlation of IRF8 expression with detectable CD37 levels. Together, this study provides new insight into the molecular mechanisms underlying differential CD37 expression in human DLBCL and reveals IRF8 as a transcriptional regulator of CD37 in B-cell lymphoma.
Differential impact of tamoxifen and aromatase inhibitors on thrombin generation: the prospective HEMOBREAST cohort
Authors: Blondon Marc , Bodmer Alexandre , Thouvenin Laure , Lecompte Thomas , Righini Marc , Fontana Pierre , Casini Alessandro 
Published: January 2022

Abstract
Tamoxifen and aromatase inhibitors (AIs) are potent antitumoral agents against breast cancer. Tamoxifen increases the risk of venous thromboembolism (VTE), but the influence of AIs on the risk of VTE remains unclear. To inform clinical decisions, we evaluated associations of tamoxifen or AIs with changes of surrogate hemostatic biomarkers. This prospective cohort included 107 women with localized breast cancer starting tamoxifen (n = 42) or an AI (n = 65). Thrombin generation (CAT) its sensitivity to thrombomodulin (TM) or activated protein C (APC), and specific coagulation parameters, were measured before and 10-16 weeks after initiation of treatmen Compared with baseline, endogenous thrombin potential and thrombin peak increased in tamoxifen users (+86 nM × min; 95% confidence interval [CI], 30-142; and +33 nM; 95% CI, 21-45) but not in AI users (n = 65; +44 nM × min; 95% CI, −4 to 93; and +7 nM; 95% CI, −3 to 17). Normalized TM sensitivity ratios increased with tamoxifen (+0.26; 95% CI, 0.19-0.33y) but not with AI (+0.02; 95% CI, −0.03 to 0.07). Plasma levels of fibrinogen, antithrombin, protein C, and Tissue Factor Pathway Inhibitor decreased, and free protein S increased with tamoxifen but not with AIs. The observed shift toward increased coagulability associated with tamoxifen is in line with its known increased risk of VTE. In contrast, AIs do not appear to impact hemostasis, suggesting a lack of associated VTE risk. The trial was registered at www.clinicaltrials.gov as #NCT03381963.
Forskolin-induced organoid swelling is associated with long-term cystic fibrosis disease progression
Authors: Muilwijk Danya , de Poel Eyleen , van Mourik Peter , Suen Sylvia W.F. , Vonk Annelotte M. , Brunsveld Jesse E. , Kruisselbrink Evelien , Oppelaar Hugo , Hagemeijer Marne C. , Berkers Gitte , de Winter-de Groot Karin M. , Heida-Michel Sabine , Jans Stephan R. , van Panhuis Hannah , van der Eerden Menno M. , van der Meer Renske , Roukema Jolt , Dompeling Edward , Weersink Els J.M. , Koppelman Gerard H. , Vries Robert , Zomer-van Ommen Domenique D. , Eijkemans Marinus J.C. , van der Ent Cornelis K. , Beekman Jeffrey M. 
Published: January 2022

RationaleCystic fibrosis (CF) is a monogenic life-shortening disease associated with highly variable individual disease progression which is difficult to predict. Here we assessed the association of forskolin-induced swelling (FIS) of patient-derived organoids with long-term CF disease progression in multiple organs and compared FIS with the golden standard biomarker sweat chloride concentration (SCC).MethodsWe retrieved 9-year longitudinal clinical data from the Dutch CF Registry of 173 people with mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Individual CFTR function was defined by FIS, measured as the relative size increase of intestinal organoids after stimulation with 0.8 µM forskolin, quantified as area under the curve (AUC). We used linear mixed-effect models and multivariable logistic regression to estimate the association of FIS with long-term forced expiratory volume in 1 s % predicted (FEV1pp) decline and development of pancreatic insufficiency, CF-related liver disease and diabetes. Within these models, FIS was compared with SCC.ResultsFIS was strongly associated with longitudinal changes of lung function, with an estimated difference in annual FEV1pp decline of 0.32% (95% CI 0.11–0.54%; p=0.004) per 1000-point change in AUC. Moreover, increasing FIS levels were associated with lower odds of developing pancreatic insufficiency (adjusted OR 0.18, 95% CI 0.07–0.46; p<0.001), CF-related liver disease (adjusted OR 0.18, 95% CI 0.06–0.54; p=0.002) and diabetes (adjusted OR 0.34, 95% CI 0.12–0.97; p=0.044). These associations were absent for SCC.ConclusionThis study exemplifies the prognostic value of a patient-derived organoid-based biomarker within a clinical setting, which is especially important for people carrying rareCFTRmutations with unclear clinical consequences.
Should knee extension strength testing be implemented as a screening test for identifying probable and confirmed sarcopenia in older T2DM patients?
Authors: kis Ofer , Buch Assaf , Eldor Roy , Rubin Amir , Dunsky Ayelet , Stern Naftali , Moran Daniel S. 
Published: January 2022

Abstract
Background
The accelerated loss of muscle strength and mass observed in older type 2 diabetes mellitus (T2DM) patients due to the combined effects of diabetes and obesity, greatly increases their risk for sarcopenia. Early detection and treatment of probable and confirmed sarcopenia is paramount to delay mobility disability. Using low handgrip strength cut-off points for the initial identification of sarcopenia according to the new European Working Group on Sarcopenia in Older People (EWGSOP2) guidelines may mask the presence of sarcopenia. Relative knee extension strength cut-off points using a simple hand-held dynamometer can assist clinicians in the diagnosis of probable and confirmed sarcopenia by possibly reducing false negative results.

Methods
A cohort of one hundred T2DM older patients (60% women) (mean age 74.5 years) mostly obese community dwelling older adults were evaluated for body composition by Bioelectrical impedance analysis (BIA), yielding appendicular skeletal mass index (ASMI) results. Patients underwent handgrip strength (HGS) and knee extension strength (KES) tests as well as functional ability tests. Prevalence of probable and confirmed sarcopenia using HGS and KES cut-off points were calculated. Pearson correlations were performed to evaluate the relationship between ASMI and limbs strength. A regression analysis was conducted to examine which variables best predict ASMI values. A multivariate analysis of covariance was performed to assess the effect of independent variables on KES and HGS.

Results
Using cutoff points for low KES identified 24 patients with probable sarcopenia and two with confirmed sarcopenia. Conversely, using the EWGSOP2 cut off points for low HGS, identified only one patient with probable sarcopenia and none of the patients with confirmed sarcopenia.

Conclusion
KES cut-off points using a simple hand-held dynamometer can assist in the identification of probable and confirmed sarcopenia using EWGSOP2 cut off points for low muscle mass in a population of older T2DM patients for further analysis and early treatment. This is notably true in patients possessing high body mass index (BMI) alongside normal ASMI and HGS, potentially reducing false positive sarcopenia screening results.

Trial registration
ClinicalTrials.gov PRS: NCT03560375. Last registration date (last update): 06/06/2018. The trial was a-priori registered before actual recruitment of subjects.