bluuebunny/crossref_metadata_2025_split huggingface dataset:
Disease-Modifying Drug Uptake and Health Service Use in the Ageing MS Population
Authors: Ng Huah Shin , Graf Jonas , Zhu Feng , Kingwell Elaine , Aktas Orhan , Albrecht Philipp , Hartung Hans-Peter , Meuth Sven G. , Evans Charity , Fisk John D. , Marrie Ruth Ann , Zhao Yinshan , Tremlett Helen 
Published: January 2022

BackgroundEvidence regarding the efficacy or effectiveness of the disease-modifying drugs (DMDs) in the older multiple sclerosis (MS) population is scarce. This has contributed to a lack of evidence-based treatment recommendations for the ageing MS population in practice guidelines. We examined the relationship between age (&lt;55 and ≥55 years), DMD exposure and health service use in the MS population.MethodsWe conducted a population-based observational study using linked administrative health data from British Columbia, Canada. We selected all persons with MS and followed from the most recent of their first MS or demyelinating event, 18th birthday or 01-January-1996 (index date) until the earliest of emigration, death or 31-December-2017 (study end). We assessed DMD exposure status over time, initially as any versus no DMD, then by generation (first or second) and finally by each individual DMD. Age-specific analyses were conducted with all-cause hospitalizations and number of physician visits assessed using proportional means model and negative binomial regression with generalized estimating equations.ResultsWe included 19,360 persons with MS (72% were women); 10,741/19,360 (56%) had ever reached their 55th birthday. Person-years of follow-up whilst aged &lt;55 was 132,283, and 93,594 whilst aged ≥55. Any DMD, versus no DMD in the &lt;55-year-olds was associated with a 23% lower hazard of hospitalization (adjusted hazard ratio, aHR0.77; 95%CI 0.72-0.82), but not in the ≥55-year-olds (aHR0.95; 95%CI 0.87-1.04). Similar patterns were observed for the first and second generation DMDs. Exposure to any (versus no) DMD was not associated with rates of physician visits in either age group (&lt;55 years: adjusted rate ratio, aRR1.02; 95%CI 1.00-1.04 and ≥55 years: aRR1.00; 95%CI 0.96-1.03), but variation in aRR was observed across the individual DMDs.ConclusionOur study showed beneficial effects of the DMDs used to treat MS on hospitalizations for those aged &lt;55 at the time of exposure. In contrast, for individuals ≥55 years of age exposed to a DMD, the hazard of hospitalization was not significantly lowered. Our study contributes to the broader understanding of the potential benefits and risks of DMD use in the ageing MS population.
Intralymphatic GAD-alum Injection Modulates B Cell Response and Induces Follicular Helper T Cells and PD-1+ CD8+ T Cells in Patients With Recent-Onset Type 1 Diabetes
Authors: Barcenilla Hugo , Pihl Mikael , Wahlberg Jeanette , Ludvigsson Johnny , Casas Rosaura 
Published: January 2022

Antigen-specific immunotherapy is an appealing strategy to preserve beta-cell function in type 1 diabetes, although the approach has yet to meet its therapeutic endpoint. Direct administration of autoantigen into lymph nodes has emerged as an alternative administration route that can improve the efficacy of the treatment. In the first open-label clinical trial in humans, injection of aluminum-formulated glutamic acid decarboxylase (GAD-alum) into an inguinal lymph node led to the promising preservation of C-peptide in patients with recent-onset type 1 diabetes. The treatment induced a distinct immunomodulatory effect, but the response at the cell level has not been fully characterized. Here we used mass cytometry to profile the immune landscape in peripheral blood mononuclear cells from 12 participants of the study before and after 15 months of treatment. The immunomodulatory effect of the therapy included reduction of naïve and unswitched memory B cells, increase in follicular helper T cells and expansion of PD-1+ CD69+ cells in both CD8+ and double negative T cells. In vitro stimulation with GAD65 only affected effector CD8+ T cells in samples collected before the treatment. However, the recall response to antigen after 15 months included induction of CXCR3+ and CD11c+Tbet+ B cells, PD-1+ follicular helper T cells and exhausted-like CD8+ T cells. This study provides a deeper insight into the immunological changes associated with GAD-alum administration directly into the lymph nodes.
β2-Adrenoceptor Deficiency Results in Increased Calcified Cartilage Thickness and Subchondral Bone Remodeling in Murine Experimental Osteoarthritis
Authors: Rösch Gundula , Muschter Dominique , Taheri Shahed , El Bagdadi Karima , Dorn Christoph , Meurer Andrea , Zaucke Frank , Schilling Arndt F. , Grässel Susanne , Straub Rainer H. , Jenei-Lanzl Zsuzsa 
Published: January 2022

PurposeRecent studies demonstrated a contribution of adrenoceptors (ARs) to osteoarthritis (OA) pathogenesis. Several AR subtypes are expressed in joint tissues and the β2-AR subtype seems to play a major role during OA progression. However, the importance of β2-AR has not yet been investigated in knee OA. Therefore, we examined the development of knee OA in β2-AR-deficient (Adrb2-/-) mice after surgical OA induction.MethodsOA was induced by destabilization of the medial meniscus (DMM) in male wildtype (WT) and Adrb2-/- mice. Cartilage degeneration and synovial inflammation were evaluated by histological scoring. Subchondral bone remodeling was analyzed using micro-CT. Osteoblast (alkaline phosphatase - ALP) and osteoclast (cathepsin K - CatK) activity were analyzed by immunostainings. To evaluate β2-AR deficiency-associated effects, body weight, sympathetic tone (splenic norepinephrine (NE) via HPLC) and serum leptin levels (ELISA) were determined. Expression of the second major AR, the α2-AR, was analyzed in joint tissues by immunostaining.ResultsWT and Adrb2-/- DMM mice developed comparable changes in cartilage degeneration and synovial inflammation. Adrb2-/- DMM mice displayed elevated calcified cartilage and subchondral bone plate thickness as well as increased epiphyseal BV/TV compared to WTs, while there were no significant differences in Sham animals. In the subchondral bone of Adrb2-/- mice, osteoblasts activity increased and osteoclast activity deceased. Adrb2-/- mice had significantly higher body weight and fat mass compared to WT mice. Serum leptin levels increased in Adrb2-/- DMM compared to WT DMM without any difference between the respective Shams. There was no difference in the development of meniscal ossicles and osteophytes or in the subarticular trabecular microstructure between Adrb2-/- and WT DMM as well as Adrb2-/- and WT Sham mice. Number of α2-AR-positive cells was lower in Adrb2-/- than in WT mice in all analyzed tissues and decreased in both Adrb2-/- and WT over time.ConclusionWe propose that the increased bone mass in Adrb2-/- DMM mice was not only due to β2-AR deficiency but to a synergistic effect of OA and elevated leptin concentrations. Taken together, β2-AR plays a major role in OA-related subchondral bone remodeling and is thus an attractive target for the exploration of novel therapeutic avenues.
Characteristics of Silicone Oil Emulsification After Vitrectomy for Rhegmatogenous Retinal Detachment: An Ultrasound Biomicroscopy Study
Authors: Zhao Hongmei , Yu Jian , Zong Yuan , Jiang Chunhui , Zhu Haohao , Xu Gezhi 
Published: January 2022

Purpose: To investigate the characteristics of silicone oil (SO) emulsification after vitrectomy for rhegmatogenous retinal detachment (RRD) and possible correlations with clinical factors.Methods: Patients who underwent primary pars plana vitrectomy with SO injection for RRD followed by SO removal at the Eye and ENT Hospital of Fudan University between January 2016 and January 2020 were included. Ultrasound biomicroscopy (UBM) images of the anterior segment were taken before SO removal. Eight signs of SO emulsification in the UBM images were graded as 1 (present) or 0 (not present) and the grades for all signs in each eye were summed. Correlations between SO emulsification grade and clinical factors were determined.Results: A total of 118 patients (118 eyes) were enrolled in this study. Emulsified SO particles were found in all 118 eyes (100%). The eight signs were more frequently detected in the superior part of the eye. The mean total SO emulsification grade was 19.99 ± 12.98 (range: 1–36). Younger age and male (both P &lt; 0.05) were associated with higher total SO emulsification grade. Patients with intraocular pressure (IOP) &gt; 21 mmHg or the use of antiglaucoma medications at the time of SO removal had a higher total SO emulsification grade, were younger, and were more frequently male (all P &lt; 0.05) than patients without ocular hypertension.Conclusions: UBM could play an important role in the diagnosis and grading of SO emulsification. Younger patients and males are more prone to SO emulsification, which may lead to elevated IOP.
Deep Learning in Prostate Cancer Diagnosis Using Multiparametric Magnetic Resonance Imaging With Whole-Mount Histopathology Referenced Delineations
Authors: Li Danyan , Han Xiaowei , Gao Jie , Zhang Qing , Yang Haibo , Liao Shu , Guo Hongqian , Zhang Bing 
Published: January 2022

Background: Multiparametric magnetic resonance imaging (mpMRI) plays an important role in the diagnosis of prostate cancer (PCa) in the current clinical setting. However, the performance of mpMRI usually varies based on the experience of the radiologists at different levels; thus, the demand for MRI interpretation warrants further analysis. In this study, we developed a deep learning (DL) model to improve PCa diagnostic ability using mpMRI and whole-mount histopathology data.Methods: A total of 739 patients, including 466 with PCa and 273 without PCa, were enrolled from January 2017 to December 2019. The mpMRI (T2 weighted imaging, diffusion weighted imaging, and apparent diffusion coefficient sequences) data were randomly divided into training (n = 659) and validation datasets (n = 80). According to the whole-mount histopathology, a DL model, including independent segmentation and classification networks, was developed to extract the gland and PCa area for PCa diagnosis. The area under the curve (AUC) were used to evaluate the performance of the prostate classification networks. The proposed DL model was subsequently used in clinical practice (independent test dataset; n = 200), and the PCa detective/diagnostic performance between the DL model and different level radiologists was evaluated based on the sensitivity, specificity, precision, and accuracy.Results: The AUC of the prostate classification network was 0.871 in the validation dataset, and it reached 0.797 using the DL model in the test dataset. Furthermore, the sensitivity, specificity, precision, and accuracy of the DL model for diagnosing PCa in the test dataset were 0.710, 0.690, 0.696, and 0.700, respectively. For the junior radiologist without and with DL model assistance, these values were 0.590, 0.700, 0.663, and 0.645 versus 0.790, 0.720, 0.738, and 0.755, respectively. For the senior radiologist, the values were 0.690, 0.770, 0.750, and 0.730 vs. 0.810, 0.840, 0.835, and 0.825, respectively. The diagnosis made with DL model assistance for radiologists were significantly higher than those without assistance (P &lt; 0.05).Conclusion: The diagnostic performance of DL model is higher than that of junior radiologists and can improve PCa diagnostic accuracy in both junior and senior radiologists.
Association of Gender, Diagnosis, and Obesity With Retention Rate of Secukinumab in Spondyloarthropathies: Results Form a Multicenter Real-World Study
Authors: García-Dorta Alicia , León-Suarez Paola , Peña Sonia , Hernández-Díaz Marta , Rodríguez-Lozano Carlos , González-Dávila Enrique , Hernández-Hernández María Vanesa , Díaz-González Federico 
Published: January 2022

Background: Secukinumab has been shown effective for psoriatic arthritis (PsA) and axial spondylarthritis (AxSpA) in randomized trials. The aim of this study was to analyze baseline patient and disease characteristics associated with a better retention rate of secukinumab under real-world conditions.Patients and Methods: Real-life, prospective multicenter observational study involving 138 patients, 61 PsA and 77 AxSpA, who were analyzed at baseline, 6, 12 months and subsequently every year after starting secukinumab regardless of the line of treatment. Demographics and disease characteristics, measures of activity, secukinumab use, and adverse events were collected. Drug survival was analyzed using Kaplan-Meier curves and factors associated with discontinuation were evaluated using Cox regression. The machine-learning J48 decision tree classifier was also applied.Results: During the 1st year of treatment, 75% of patients persisted with secukinumab, but accrued 71% (n = 32) in total losses (n = 45). The backward stepwise (Wald) method selected diagnosis, obesity, and gender as relevant variables, the latter when analyzing the interactions. At 1 year of follow-up, the Cox model showed the best retention rate in the groups of AxSpa women (95%, 95% CI 93–97%) and PsA men (89%, 95% CI 84–93%), with the worst retention in PsA women (66%, 95% CI 54–79%). The J48 predicted secukinumab retention with an accuracy of 77.2%. No unexpected safety issues were observed.Conclusions: Secukinumab shows the best retention rate at 1 year of treatment in AxSpA women and in PsA men, independently of factors such as the time of disease evolution, the line of treatment or the initial dose of the drug.
Decreased CDKL2 Expression in Clear Cell Renal Cell Carcinoma Predicts Worse Overall Survival
Authors: Chen Zhan , Lv Yan , He Lu , Wu Shunli , Wu Zhuang 
Published: January 2022

Background: Clear cell renal cell carcinoma (ccRCC) is the most frequent and lethal type of kidney cancer. Although differential expression of cyclin-dependent kinase-like 2 (CDKL2) has been reported to be associated with tumor progression in other cancers, its prognostic value, and potential mechanism in patients with ccRCC still remain unknown.Methods: Gene expression analysis was conducted using The Cancer Genome Atlas (TCGA), Gene Expression Omnibus, and International Cancer Genome Consortium databases. Further, clinicopathologic analysis; Kaplan–Meier survival analysis; weighted gene co-expression network analysis; gene set enrichment analysis; gene ontology enrichment; methylation; and immune infiltration analyses were performed using TCGA-kidney renal clear cell carcinoma profiles. CDKL2 translational levels were analyzed using The Human Protein Atlas database.Results:CDKL2 expression was decreased in ccRCC samples retrieved from the four databases. Gender, survival status, histologic grade, clinical stage, TNM classification, and tumor status were closely related to CDKL2 expression. In addition, CDKL2 downregulation was an independent prognostic factor for poor prognosis in multivariate analysis. Enrichment analyses using multiple tests revealed that CDKL2 is not just closely related to immune response but this association is highly correlated as well. Further, we found that CDKL2 expression was significantly correlated with the infiltration levels of T cell CD4 memory resting; monocytes; macrophages M0, M1, and M2; dendritic cells resting; mast cells resting; plasma cells; T cell CD8; and T cell regulatory.Conclusion: This is the first report to study the expression of CDKL2 in ccRCC, wherein we suggest that decreased CDKL2 expression is closely correlated with poor prognosis in ccRCC. We consider that CDKL2 is a novel and potential prognostic biomarker associated with immune infiltrates in ccRCC.
Monthly At-Home Computerized Cognitive Testing to Detect Diminished Practice Effects in Preclinical Alzheimer's Disease
Authors: Jutten Roos J. , Rentz Dorene M. , Fu Jessie F. , Mayblyum Danielle V. , Amariglio Rebecca E. , Buckley Rachel F. , Properzi Michael J. , Maruff Paul , Stark Craig E. , Yassa Michael A. , Johnson Keith A. , Sperling Reisa A. , Papp Kathryn V. 
Published: January 2022

Introduction: We investigated whether monthly assessments of a computerized cognitive composite (C3) could aid in the detection of differences in practice effects (PE) in clinically unimpaired (CU) older adults, and whether diminished PE were associated with Alzheimer's disease (AD) biomarkers and annual cognitive decline.Materials and Methods:N = 114 CU participants (age 77.6 ± 5.0, 61% female, MMSE 29 ± 1.2) from the Harvard Aging Brain Study completed the self-administered C3 monthly, at-home, on an iPad for one year. At baseline, participants underwent in-clinic Preclinical Alzheimer's Cognitive Composite-5 (PACC5) testing, and a subsample (n = 72, age = 77.8 ± 4.9, 59% female, MMSE 29 ± 1.3) had 1-year follow-up in-clinic PACC5 testing available. Participants had undergone PIB-PET imaging (0.99 ± 1.6 years before at-home baseline) and Flortaucipir PET imaging (n = 105, 0.62 ± 1.1 years before at-home baseline). Linear mixed models were used to investigate change over months on the C3 adjusting for age, sex, and years of education, and to extract individual covariate-adjusted slopes over the first 3 months. We investigated the association of 3-month C3 slopes with global amyloid burden and tau deposition in eight predefined regions of interest, and conducted Receiver Operating Characteristic analyses to examine how accurately 3-month C3 slopes could identify individuals that showed &gt;0.10 SD annual decline on the PACC-5.Results: Overall, individuals improved on all C3 measures over 12 months (β = 0.23, 95% CI [0.21–0.25], p &lt; 0.001), but improvement over the first 3 months was greatest (β = 0.68, 95% CI [0.59–0.77], p &lt; 0.001), suggesting stronger PE over initial repeated exposures. However, lower PE over 3 months were associated with more global amyloid burden (r = −0.20, 95% CI [−0.38 – −0.01], p = 0.049) and tau deposition in the entorhinal cortex (r = −0.38, 95% CI [−0.54 – −0.19], p &lt; 0.001) and inferior-temporal lobe (r = −0.23, 95% CI [−0.41 – −0.02], p = 0.03). 3-month C3 slopes exhibited good discriminative ability to identify PACC-5 decliners (AUC 0.91, 95% CI [0.84–0.98]), which was better than baseline C3 (p &lt; 0.001) and baseline PACC-5 scores (p = 0.02).Conclusion: While PE are commonly observed among CU adults, diminished PE over monthly cognitive testing are associated with greater AD biomarker burden and cognitive decline. Our findings imply that unsupervised computerized testing using monthly retest paradigms can provide rapid detection of diminished PE indicative of future cognitive decline in preclinical AD.
Apathy, Executive Function, and Emotion Recognition Are the Main Drivers of Functional Impairment in Behavioral Variant of Frontotemporal Dementia
Authors: Musa Salech Gada , Lillo Patricia , van der Hiele Karin , Méndez-Orellana Carolina , Ibáñez Agustín , Slachevsky Andrea 
Published: January 2022

Background: The cognitive and neuropsychiatric deficits present in patients with behavioral variant frontotemporal dementia (bvFTD) are associated with loss of functionality in the activities of daily living (ADLs). The main purpose of this study was to examine and explore the association between the cognitive and neuropsychiatric features that might prompt functional impairment of basic, instrumental, and advanced ADL domains in patients with bvFTD.Methods: A retrospective cross-sectional study was conducted with 27 patients with bvFTD in its early stage (&lt;2 years of evolution) and 32 healthy control subjects. A neuropsychological assessment was carried out wherein measures of cognitive function and neuropsychiatric symptoms were obtained. The informant-report Technology–Activities of Daily Living Questionnaire was used to assess the percentage of functional impairment in the different ADL domains. To identify the best determinants, three separate multiple regression analyses were performed, considering each functional impairment as the dependent variable and executive function, emotion recognition, disinhibition, and apathy as independent variables.Results: For the basic ADLs, a model that explains 28.2% of the variability was found, in which the presence of apathy (β = 0.33, p = 0.02) and disinhibition (β = 0.29, p = 0.04) were significant factors. Concerning instrumental ADLs, the model produced accounted for 63.7% of the functional variability, with the presence of apathy (β = 0.71, p &lt; 0.001), deficits in executive function (β = −0.36, p = 0.002), and lack of emotion recognition (β = 0.28, p = 0.017) as the main contributors. Finally, in terms of advanced ADLs, the model found explained 52.6% of the variance, wherein only the presence of apathy acted as a significant factor (β = 0.59, p &lt; 0.001).Conclusions: The results of this study show the prominent and transverse effect of apathy in the loss of functionality throughout all the ADL domains. Apart from that, this is the first study that shows that the factors associated with loss of functionality differ according to the functional domain in patients with bvFTD in its early stage. Finally, no other study has analyzed the impact of the lack of emotion recognition in the functionality of ADLs. These results could guide the planning of tailored interventions that might enhance everyday activities and the improvement of quality of life.
Efficacy of Neuroendoscopic Treatment for Septated Chronic Subdural Hematoma
Authors: Deng Jianhong , Wang Fangyu , Wang Haojie , Zhao Mingpei , Chen Guorong , Shangguan Huangcheng , Yu Lianghong , Jiang Changzhen , Fang Wenhua , Yao Peisen , Kang Dezhi , Zheng Shufa 
Published: January 2022

Objective: Neuroendoscopic treatment is an alternative therapeutic strategy for the treatment of septate chronic subdural hematoma (sCSDH). However, the safety and efficacy of this strategy remain controversial. We compared the clinical outcomes of neuroendoscopic treatment with those of standard (large bone flap) craniotomy for sCSDH reported in our center. Furthermore, the safety and efficacy of the neuroendoscopic treatment procedure for sCSDH were evaluated.Methods: We retrospectively collected the clinical data of 43 patients (37 men and six women) with sCSDH who underwent either neuroendoscopic treatment or standard (large bone flap) craniotomy, such as sex, age, smoking, drinking, medical history, use of antiplatelet drugs, postoperative complications, sCSDH recurrence, length of hospital stay, and postoperative hospital stay. We recorded the surgical procedures and the neurological function recovery prior to surgery and 6 months following the surgical treatment.Results: The enrolled patients were categorized into neuroendoscopic treatment (n = 23) and standard (large bone flap) craniotomy (n = 20) groups. There were no differences in sex, age, smoking, drinking, medical history, antiplatelet drug use, postoperative complications, and sCSDH recurrence between the two groups (p &gt; 0.05). However, the patients in neuroendoscopic treatment group had a shorter length of total hospital stay and postoperative hospital stay as compared with the standard craniotomy group (total hospital stay: 5.26 ± 1.89 vs. 8.15 ± 1.04 days, p &lt; 0.001; postoperative hospital stay: 4.47 ± 1.95 vs. 7.96 ± 0.97 days, p &lt; 0.001). The imaging and Modified Rankin Scale at the 6-month follow-up were satisfactory, and no sCSDH recurrence was reported in the two groups.Conclusions: The findings of this study indicate that neuroendoscopic treatment is safe and effective for sCSDH; it is minimally invasive and could be clinically utilized.