bluuebunny/crossref_metadata_2025_split huggingface dataset:
Measurement Properties of the High-Level Mobility Assessment Tool for Mild Traumatic Brain Injury
Authors: Kleffelgaard Ingerid , Roe Cecile , Sandvik Leiv , Hellstrom Torgeir , Soberg Helene L. 
Published: March 2013

BackgroundThe High-Level Mobility Assessment Tool (HiMAT) was developed to quantify balance and mobility problems after traumatic brain injury (TBI). Measurement properties of the HiMAT have not been tested in the mild TBI (MTBI) population.ObjectiveThe aim of this study was to examine the reliability, validity, and responsiveness of the HiMAT in a sample of the MTBI population.DesignA cohort, pretest-posttest, comparison study was conducted.MethodsNinety-two patients (69% men, 31% women) with a mean age of 37.1 years (SD=13.8) and a mean Glasgow Coma Scale score of 14.7 (SD=0.7) were recruited from Oslo University Hospital. All patients were tested with the HiMAT (range of scores=0 [worst] to 54 [best]) at 3 months postinjury. Fifty-one patients were retested at 6 months. A subgroup of 25 patients was selected for the reliability testing. Balance function reported on the Rivermead Post Concussion Symptoms Questionnaire was chosen as a criterion and anchor. Criterion-related validity was studied with correlation analysis. Intraclass correlation coefficients (ICCs) were used for assessing interrater and intrarater reliability. Minimal detectable change (MDC) for the HiMAT was estimated. Responsiveness was assessed with receiver operating characteristic curve analyses.ResultsThe mean HiMAT sum score was 46.2 (95% confidence interval=44.4 to 48.1). The HiMAT had a ceiling effect of 22.8%. The correlation between HiMAT scores and self-reported balance problems was large (r=−.63, P&lt;.001). Interrater and intrarater reliability of the HiMAT sum score was high (interrater ICC=.99, intrarater ICC=.95). The MDC was −3 to +4 points. Responsiveness was good, and the HiMAT discriminated well between patients with self-perceived improved balance function versus unchanged balance function (area under the curve=0.86).LimitationsThe small sample size, a ceiling effect, and lack of a gold standard were limitations of the study.ConclusionsThe HiMAT demonstrated satisfactory measurement properties for patients with MTBI. The HiMAT can be used as an outcome measure of balance and mobility problems in patients with MTBI.
Gene Expression of Catalytic Proteasome Subunits and Resistance Toward Proteasome Inhibition of B Lymphocytes from Patients with Primary Sjögren Syndrome
Authors: Martinez-Gamboa Lorena , Lesemann Karsten , Kuckelkorn Ulrike , Scheffler Sonja , Ghannam Khetam , Hahne Martin , Gaber-Elsner Timo , Egerer Karl , Naumann Lydia , Buttgereit Frank , Dörner Thomas , Kloetzel Peter M. , Burmester Gerd R. , Faustman Denise L. , Feist Eugen 
Published: March 2013

Objective.Dysregulation of proteasome subunit β1i expression has been shown in total blood mononuclear cells (PBMC) from patients with primary Sjögren syndrome (pSS), a B cell-driven systemic autoimmune disorder.Methods.Proteasome activation was investigated in sorted blood cells from patients with pSS and controls by measuring transcript levels of constitutive (β1/β2/β5) and corresponding immunoproteasome catalytic subunits (β1i/β2i/β5i) using real-time PCR. At protein level, β1i protein expression was analyzed by immunoblotting. Functional effects of proteasome inhibition on proteolytic activity and induction of apoptosis were also evaluated in cellular subsets.Results.The proteasome was found to be activated in pSS, with upregulation of gene expression of catalytic proteasome subunits. Western blot analysis revealed decreased β1i protein expression in pSS B lymphocytes, with decreased protein despite increased messenger RNA (mRNA) levels. After proteasome inhibitionin vitro, proteolytic activity was less reduced and resistance to apoptosis was increased in B lymphocytes compared to other cells.Conclusion.In pSS, catalytic subunits of the proteasome are upregulated at the mRNA level, while dysregulation of subunit β1i is attributed to B lymphocytes. B cell resistance after proteasome inhibition differs from the classical concept of increased susceptibility toward inhibition in activated cells, supporting the novel notion that susceptibility depends on cellular intrinsic factors and on proteasome activation.
Comparison of EuroQol-5D and Short Form-6D Utility Scores in Multiethnic Asian Patients with Psoriatic Arthritis: A Cross-sectional Study
Authors: Leung Ying-Ying , Png May-Ee , Wee Hwee-Lin , Thumboo Julian 
Published: March 2013

Objective.To compare EuroQol-5D (EQ-5D) and Short Form-6D (SF-6D) utility scores in multiethnic Asian patients with psoriatic arthritis (PsA).Methods.Consecutive patients fulfilling the Classification Criteria for Psoriatic Arthritis attending a rheumatology outpatient clinic were recruited and completed the EQ-5D and SF-6D questionnaires. Comparisons were performed by score distribution, mean, median, and the Outcome Measures in Rheumatology filter: i.e., truth, discrimination, and feasibility.Results.Eighty-six patients were enrolled (69 English-speaking and 17 Chinese-speaking; male:female ratio 0.91). The score distribution of SF-6D was normal, while that of EQ-5D was bimodal. A ceiling effect was observed in 20% of patients for EQ-5D and none for SF-6D. There were moderate correlations (Spearman’s rho = 0.59, p < 0.0001) between the 2 scores, but poor agreements on scatterplot, intraclass correlation (ICC 0.43 and standardized ICC 0.21), and Bland-Altman plots. EQ-5D generated lower utility scores than SF-6D in the poorer health subgroup. SF-6D had stronger correlation with the general health status and other external measures of health; and it distinguished better between good and poor general health status, with better effect size and relative efficiency statistics. EQ-5D demonstrated higher patient acceptability.Conclusion.EQ-5D and SF-6D instruments generated different utility scores in PsA. SF-6D may be superior because of normal scaling distribution and the absence of ceiling and floor effects. SF-6D also had better construct validity and better discrimination of poor health status. More studies are required for cost-utility analysis in PsA.
Priming Primary Care Physicians to Treat Osteoporosis After a Fragility Fracture: An Integrated Multidisciplinary Approach
Authors: Roux Sophie , Beaulieu Michèle , Beaulieu Marie-Claude , Cabana François , Boire Gilles 
Published: March 2013

Objective.To evaluate 2 incremental levels of intervention designed to increase initiation of osteoporosis treatment by primary care physicians (PCP) following fragility fractures (FF).Methods.Women and men over age 50 years were screened for incident FF in fracture clinics, and eligible outpatients were randomly assigned to standard care (SC) or to either minimal (MIN) or intensive (INT) interventions. The MIN and INT interventions were intended to educate and motivate both patients and PCP, but differed in their frequency of contact and information content. Delivery of osteoporosis medication was confirmed with pharmacists. Treatment rates were analyzed using an intention-to-treat approach.Results.At inclusion, 74.3% of 881 outpatients with FF were untreated. Followup at 12 months was completed in 92.3% of patients. Up to 90% of patients treated at inclusion remained treated at 12 months. Among patients who initially were untreated, 18.8% in the SC group, 40.4% in the MIN, and 53.2% in the INT groups were treated at 12 months. Change in treatment rates (adjusted for age and initial treatment) increased significantly after both MIN and INT. Only the INT intervention significantly increased treatment rates in patients with previous fractures. Negative predictors of change in treatment status included non-major FF, age younger than 65 years, and male sex.Conclusion.Both interventions significantly increased initiation of osteoporosis treatment. Our multidisciplinary intervention builds on existing first-line structures and uses minimal specialized resources. Iterative and systematic interventions in the context of clinical care may modify the approach of PCP to osteoporosis management after FF and narrow the care gap in the long term.
First-degree Relatives of Patients with Rheumatoid Arthritis Exhibit High Prevalence of Joint Symptoms
Authors: Smolik Irene , Robinson David B. , Bernstein Charles N. , El-Gabalawy Hani S. 
Published: March 2013

Objective.The preclinical period of rheumatoid arthritis (RA) is characterized by the presence of autoantibodies such as anticitrullinated protein antibodies (ACPA) and rheumatoid factor (RF). Little is known about the joint symptom profile preceding onset of RA, and whether symptoms are associated with RA autoantibodies. Because first-degree relatives (FDR) of North American Native (NAN) RA probands exhibit multiple risk factors for development of future RA, we investigated the prevalence of joint symptoms in this high-risk population.Methods.We studied 306 FDR of NAN patients with RA, 323 NAN controls (NC), and 293 white controls (WC) having no family history of autoimmune diseases. Study subjects completed a questionnaire that asked whether they had pain, swelling, or morning stiffness in their hand joints, or in other joints. Serum samples were gathered at the same time and tested for the presence of ACPA, RF, and high-sensitivity C-reactive protein levels.Results.In all cases, FDR were significantly more likely to report experiencing joint symptoms compared to the 2 control groups. FDR also exhibited a significantly higher prevalence of RA autoantibodies than the control groups. There were modest trends for joint symptoms to associate with RA autoantibodies, and individuals who were both ACPA-positive and RF-positive had the highest prevalence of joint symptoms.Conclusion.FDR of NAN patients with RA have a higher prevalence of joint symptoms compared to individuals with no family history of autoimmune disease. This finding is only partially explained by a high prevalence of RA autoantibodies in the FDR.
Do Changing Toll-like Receptor Profiles in Different Layers and Grades of Osteoarthritis Cartilage Reflect Disease Severity?
Authors: Barreto Gonçalo , Sillat Tarvo , Soininen Antti , Ylinen Pekka , Salem Abdelhakim , Konttinen Yrjö T. , Al-Samadi Ahmed , Nordström Dan C.E. 
Published: March 2013

Objective.Cartilage degeneration in osteoarthritis (OA) leads to release of potential danger signals. The aim of our study was to profile OA cartilage for the Toll-like receptor (TLR) danger signal receptors.Methods.Osteochondral cylinders from total knee replacements were graded using OA Research Society International score and stained for proteoglycans, collagenase-cleaved type II collagen, and TLR 1–10, which were analyzed histomorphometrically.Results.Grade 1 OA lesions contained 22%–55% TLR 1–9-positive cells in the surface zone, depending on the TLR type. In Grade 2 TLR, immunoreactivity was 60%–100% (p < 0.01) and it was even higher in Grades 3 and 4 (p < 0.01 vs Grade 1). TLR-positive cells in Grade 1 middle zone were low, 0–19.9%, but were 5.1%–32.7% in Grade 2 (p < 0.01) and 34%–83% in Grades 3–4 samples (p < 0.001). TLR values in Grade 5 were low (14.3%–28.7%; p < 0.001). In Grades 3–4 OA, cartilage matrix stained strongly for TLR. In Grade 1, COL2-3/4M was restricted to chondrocytes, but was increasingly seen in matrix upon progress of OA to Grade 4, and then declined.Conclusion.Cells in the gliding surface zone are fully equipped with TLR in mild OA. Their proportion increases and extends to the middle or even the deep zone, reflecting OA progression. COL2A-3/4M staining suggests Endo180-mediated intake for intralysosomal degradation by cathepsins in Grade 1, but in higher grades this chondrocyte-mediated clearance fails and the matrix demonstrates extensive collagenase-induced damage. Detached and/or partially degraded matrix components can then act as endogenous danger signals (damage-associated molecular patterns or DAMP) and stimulate increasingly TLR-equipped chondrocytes to inflammation. At the peak inflammatory response, soluble TLR may exert negative feedback, explaining in part the low TLR levels in Grade 5 OA.
Monocyte- and Macrophage-Targeted NADPH Oxidase Mediates Antifungal Host Defense and Regulation of Acute Inflammation in Mice
Authors: Grimm Melissa J. , Vethanayagam R. Robert , Almyroudis Nikolaos G. , Dennis Carly G. , Khan A. Nazmul H. , D’Auria Anthony C. , Singel Kelly L. , Davidson Bruce A. , Knight Paul R. , Blackwell Timothy S. , Hohl Tobias M. , Mansour Michael K. , Vyas Jatin M. , Röhm Marc , Urban Constantin F. , Kelkka Tiina , Holmdahl Rikard , Segal Brahm H. 
Published: March 2013

Abstract
Chronic granulomatous disease, an inherited disorder of the NADPH oxidase in which phagocytes are defective in the generation of superoxide anion and downstream reactive oxidant species, is characterized by severe bacterial and fungal infections and excessive inflammation. Although NADPH oxidase isoforms exist in several lineages, reactive oxidant generation is greatest in neutrophils, where NADPH oxidase has been deemed vital for pathogen killing. In contrast, the function and importance of NADPH oxidase in macrophages are less clear. Therefore, we evaluated susceptibility to pulmonary aspergillosis in globally NADPH oxidase–deficient mice versus transgenic mice with monocyte/macrophage-targeted NADPH oxidase activity. We found that the lethal inoculum was &gt;100-fold greater in transgenic versus globally NADPH oxidase–deficient mice. Consistent with these in vivo results, NADPH oxidase in mouse alveolar macrophages limited germination of phagocytosed Aspergillus fumigatus spores. Finally, globally NADPH oxidase–deficient mice developed exuberant neutrophilic lung inflammation and proinflammatory cytokine responses to zymosan, a fungal cell wall–derived product composed principally of particulate β-glucans, whereas inflammation in transgenic and wild-type mice was mild and transient. Taken together, our studies identify a central role for monocyte/macrophage NADPH oxidase in controlling fungal infection and in limiting acute lung inflammation.
PU.1-Dependent Transcriptional Regulation of miR-142 Contributes to Its Hematopoietic Cell–Specific Expression and Modulation of IL-6
Authors: Sun Yaping , Sun John , Tomomi Toubai , Nieves Evelyn , Mathewson Nathan , Tamaki Hiroya , Evers Rebecca , Reddy Pavan 
Published: March 2013

Abstract
MicroRNAs (miRs) have emerged as critical modulators of immune responses, but little is known about their transcriptional regulation and tissue specificity. miR-142 is specifically expressed in hematopoietic tissues and plays an important role in regulating immunity. In this study we identified the key transcriptional elements for regulation of miR-142 and its impact on TLR4-mediated expression of IL-6. The PU.1, C/EBPβ, and Runx1 transcription factor binding sites are conserved and constitutively occupied by the respective transcription factors in the miR-142 gene promoter only in the hematopoietic cells. Specific knockdown experiments in hematopoietic cells and rescue experiments in nonhematopoietic cells show that PU.1 is critical for miR-142 gene expression and that it synergizes with Runx1, C/EBPβ, and CBFβ. Furthermore, TLR4 stimulation enhanced miR-155 whereas experiments with knockdown and mimic expression of miR-155 demonstrated that miR-155 negatively regulates miR-142-3p expression by targeting PU.1. Thus, TLR4 stimulation represses PU.1, resulting in downregulation of miR-142 and increased expression of IL-6. These results collectively reveal the direct cis-acting sequences of miR-142 specific promoter and that transcription factor PU.1 is necessary for its exclusive expression in hematopoietic cells and regulation of IL-6.
Probiotics and Antibiotic-Induced Microbial Aberrations in Children
Authors: Dierikx Thomas H. , Malinowska Anna M. , Łukasik Jan , Besseling-van der Vaart Isolde , Belzer Clara , Szajewska Hania , de Meij Tim G. J. , van der Schoor Sophie R. D. , Chegary Malika , Koning Catharina (Karen) J.M. , Hanemaaijer Mark ,   Multispecies Probiotic in AAD Study Group
Published: July 2024

ImportanceProbiotics are often considered in children to prevent antibiotic-associated diarrhea. However, the underlying mechanistic effects and impact of probiotics on antibiotic-induced microbiota changes are not well understood.ObjectiveTo investigate the effects of a multispecies probiotic on the gut microbiota composition in children receiving antibiotics.Design, Setting, and ParticipantsThis is a secondary analysis of a randomized, quadruple-blind, placebo-controlled clinical trial from February 1, 2018, to May 31, 2021, including 350 children receiving broad-spectrum antibiotics in the inpatient and outpatient settings. Patients were followed up until 1 month after the intervention period. Fecal samples and data were analyzed between September 1, 2022, and February 28, 2023. Eligibility criteria included 3 months to 18 years of age and recruitment within 24 hours following initiation of broad-spectrum systemic antibiotics. In total, 646 eligible patients were approached and 350 participated in the trial.InterventionParticipants were randomly assigned to receive daily placebo or a multispecies probiotic formulation consisting of 8 strains from 5 different genera during antibiotic treatment and for 7 days afterward.Main Outcomes and MeasuresFecal stool samples were collected at 4 predefined times: (1) inclusion, (2) last day of antibiotic use, (3) last day of the study intervention, and (4) 1 month after intervention. Microbiota analysis was performed by 16S ribosomal RNA gene sequencing.ResultsA total of 350 children were randomized and collected stool samples from 88 were eligible for the microbiota analysis (54 boys and 34 girls; mean [SD] age, 47.09 [55.64] months). Alpha diversity did not significantly differ between groups at the first 3 times. Shannon diversity (mean [SD], 3.56 [0.75] vs 3.09 [1.00]; P = .02) and inverse Simpson diversity (mean [SD], 3.75 [95% CI, 1.66-5.82] vs −1.31 [95% CI, −3.17 to 0.53]; P = 1 × 10−4) indices were higher in the placebo group compared with the probiotic group 1 month after intervention. Beta diversity was not significantly different at any of the times. Three of 5 supplemented genera had higher relative abundance during probiotic supplementation, but this difference had disappeared after 1 month.Conclusions and RelevanceThe studied probiotic mixture had minor and transient effects on the microbiota composition during and after antibiotic treatment. Further research is needed to understand their working mechanisms in manipulating the microbiome and preventing antibiotic-associated dysbiosis and adverse effects such as antibiotic-associated diarrhea.Trial RegistrationClinicalTrials.gov Identifier: NCT03334604
Real‐world performance of plasma p‐tau181 in a heterogeneous memory clinic cohort
Authors: Parvizi Tandis , Wurm Raphael , König Theresa , Silvaieh Sara , Altmann Patrick , Klotz Sigrid , Regelsberger Guenther , Traub‐Weidinger Tatjana , Gelpi Ellen , Stögmann Elisabeth 
Published: July 2024

AbstractObjectiveIn light of clinical trials and disease‐modifying therapies, an early identification of patients at‐risk of developing Alzheimer's disease (AD) is crucial. Blood‐based biomarkers have shown promising results regarding the in vivo detection of the earliest neuropathological changes in AD. Herein, we investigated the ability of plasma p‐tau181 to act as a prescreening marker for amyloid positivity in a heterogeneous memory clinic‐based cohort.MethodsIn this retrospective cross‐sectional study, we included a total of 115 patients along the clinical AD continuum (mild cognitive impairment [MCI] due to AD, n = 62, probable AD dementia, n = 53). Based on their biomarker status, they were stratified into an amyloid‐positive (Aβ+, n = 88) or amyloid‐negative cohort (Aβ−, n = 27). Plasma and CSF p‐tau181 concentrations were quantified using an ultrasensitive single‐molecule array (SIMOA©). Furthermore, age‐ and sex‐adjusted receiver operating characteristic (ROC) curves were calculated and the area under the curve (AUC) of each model was compared using DeLong's test for correlated AUC curves.ResultsThe median (interquartile range [IQR]) concentration of plasma p‐tau181 was significantly higher in Aβ+ patients (3.6 pg/mL [2.5–4.6]), compared with Aβ− patients (1.7 pg/mL [1.2–1.9], p < 0.001). Regarding the distinction between Aβ+ and Aβ− patients and the prediction of amyloid positivity, a high diagnostic accuracy for plasma p‐tau181 with an AUC of 0.89 (95% CI = 0.82–0.95) was calculated. Adding the risk factors, age and APOE4, to the model did not significantly improve its performance.InterpretationOur findings demonstrate that plasma p‐tau181 could be a noninvasive and feasible prescreening marker for amyloid positivity in a heterogeneous clinical AD cohort and therefore help in identifying those who would benefit from more invasive assessment of amyloid pathology.
Biomass Chitin Nanofiber Separators Proactively Stabilizing Zinc Anodes for Dendrite‐Free Aqueous Zinc‐Ion Batteries
Authors: Wang Qunhao , Zhao Jiangqi , Zhang Jian , Li Mei , Tan Feipeng , Xue Xiaolin , Sui Zengyan , Zou Yuefei , Zhang Xi , Zhang Wei , Lu Canhui 
Published: July 2024

AbstractAqueous zinc‐ion batteries (ZIBs) have generated extensive research attention for stationary energy storage, due to their advantaged superiority in terms of inherent safety, low cost, and eco‐friendliness. However, uncontrollable dendrite growth and side reactions of the Zn anode affect the cycle life of ZIBs. Conventional separators are almost ineffective in inhibiting these issues. Herein, a chitin nanofiber membrane separator is developed to tackle these issues via a simple, low‐cost, and scalable strategy. The obtained separator exhibits abundant zincophilic functional groups, homogeneous nanopores, and excellent mechanical properties, which facilitate the desolvation of hydrated Zn2+ ions, improve the Zn2+ transference number, and homogenize the ion flux, simultaneously. Moreover, the separator can also reduce the deposition barrier, and accelerate Zn2+ deposition kinetics. Therefore, Zn dendrites and harmful side reactions are effectively and synchronously suppressed, enabling the assembled ZIBs with an ultralong cycle life and good rate capability. Impressively, the assembled Zn‐MnO2 pouch cell exhibits excellent stability and safety under various external damages. The above highlights mark a significant step toward the practical application of ZIBs.
Enhancing Volumetric Energy Density of LiFePO4 Battery Using Liquid Metal as Conductive Agent
Authors: Zhu Renjie , Liu Ganxiong , Qu Ge , Li Xueyang , Chen Xinlong , Wan Wang , Wang Chao , Huang Yunhui 
Published: July 2024

AbstractLithium iron phosphate (LiFePO4) is a widely utilized cathode material in lithium‐ion batteries, prized for its safety, low cost, and extensive cycling lifespan. However, its low compaction density limits its application in batteries requiring high volumetric energy density. The inclusion of conductive carbon black in electrodes, while increasing porosity, also exacerbates side reactions due to its high specific surface area. In this study, the use of liquid metal (GaIn) nanoparticles is explored as a substitute for carbon black in electrode formulations. GaIn nanoparticles' stable oxide film prevents oxidation at cathode potential. Additionally, liquid metal improves the particle interface to a solid‐liquid interface, reducing particle friction and providing a lubricating effect, resulting in a denser electrode structure. As a result, the porosity of LiFePO4 electrodes prepared with liquid metal is reduced, leading to a 20.7% increase in volumetric energy density. Moreover, GaIn‐containing batteries exhibit fewer side reactions, especially at elevated temperatures in both liquid and solid battery configurations. Solid‐state batteries employing GaIn nanoparticles demonstrate a specific capacity of 144 mAh g−1 at 0.5C, showcasing superior cycling performance compared to traditional formulations. This underscores the potential of GaIn to elevate the performance of LiFePO4 batteries.