bluuebunny/crossref_metadata_2025_split huggingface dataset:
Discordance of Global Assessments by Patient and Physician Is Higher in Female than in Male Patients Regardless of the Physician’s Sex: Data on Patients with Rheumatoid Arthritis, Axial Spondyloarthritis, and Psoriatic Arthritis from the DANBIO Registry
Authors: Lindström Egholm Cecilie , Krogh Niels Steen , Pincus Theodore , Dreyer Lene , Ellingsen Torkell , Glintborg Bente , Kowalski Marcin Ryszard , Lorenzen Tove , Madsen Ole Rintek , Nordin Henrik , Rasmussen Claus , Hetland Merete Lund 
Published: August 2015

Objective.To assess the frequency of discordance in patient’s (PtGA) and physician’s (PGA) global assessment, and to investigate whether higher discordance in female patients compared with male patients is associated with the physician’s sex in patients with rheumatoid arthritis (RA), axial spondyloarthritis (axSpA), and psoriatic arthritis (PsA).Methods.PtGA, PGA, and other patient-related variables were retrieved from the Danish DANBIO registry, used nationwide to monitor patients with RA, axSpA, and PsA. A questionnaire was sent to all physicians registering in DANBIO (n = 265) regarding individual physician characteristics including sex and age. Discordance was defined as PtGA > 20 mm higher (or lower) than PGA. First encounters between patients and physicians were analyzed using descriptive statistics and mixed model regression analysis.Results.Ninety physicians (34%) returned the questionnaire and were pairwise matched with 10,282 first patient encounters (8300 patients with RA, 524 axSpA, and 1458 PsA). The frequency of discordant (PtGA > PGA) encounters (not including PGA > PtGA seen in < 2%) in RA, axSpA, and PsA was 49.0%, 48.3%, and 56.5%, respectively. Discordance was more common in female patients with high scores on functional disability, pain, and fatigue across the 3 diseases, whereas it was independent of the physician’s sex.Conclusion.In this study on Danish patients with RA, axSpA, and PsA, the PtGA was > 20 mm higher than the PGA in about half of the encounters, and more common in female patients of both female and male physicians. This finding highlights one of the challenges in shared decision making.
Work Disability in Early Systemic Sclerosis: A Longitudinal Population-based Cohort Study
Authors: Sandqvist Gunnel , Hesselstrand Roger , Petersson Ingemar F. , Kristensen Lars Erik 
Published: August 2015

Objective.To study work disability (WD) with reference to levels of sick leave and disability pension in early systemic sclerosis (SSc).Methods.Patients with SSc living in the southern part of Sweden with onset of their first non-Raynaud symptom between 2003 and 2009 and with a followup of 36 months were included in a longitudinal study. Thirty-two patients (26 women, 24 with limited SSc) with a median age of 47.5 years (interquartile range 43–53) were identified. WD was calculated in 30-day intervals from 12 months prior to disease onset until 36 months after, presented as the prevalence of WD per year (0–3) and as the period prevalence of mean net days per month (± SD). Comparisons were made between patients with different disease severity and sociodemographic characteristics, and between patients and a reference group (RG) from the general population.Results.Seventy-eight percent had no WD 1 year prior to disease onset, which decreased to 47% after 3 years. The relative risk for WD in patients with SSc compared with RG was 0.95 (95% CI 0.39–2.33) at diagnosis, and increased to 2.41 (1.28–4.55) after 3 years. There were no significant correlations between WD and disease severity, but between WD and years at workplace (rs= −0.72; p = 0.002), education (rs= −0.51; p = 0.004), and sickness absence the month before disease onset (rs= 0.58; p = 0.001), respectively.Conclusion.Considerable increase in WD was noted 3 years after disease onset. Limited education, fewer years at workplace, and sickness absence before disease onset may be risk factors for sustained WD.
Comparison of Photo Optical Imaging with Musculoskeletal Ultrasound and Clinical Examination in the Assessment of Inflammatory Activity in Proximal Interphalangeal Joints in Rheumatoid Arthritis and Osteoarthritis
Authors: Amitai Isabella , Werner Stephanie , Schicke Bernd , Burmester Gerd-Rüdiger , Minet Olaf , Zabaryło Urszula , Backhaus Marina , Ohrndorf Sarah 
Published: August 2015

Objective.Lightscan is a novel, rapid, low-cost, easily operated and noninvasive imaging technology used to assess inflammatory activity in proximal interphalangeal (PIP) joints. The results are calculated automatically. To our knowledge, this is the first comparative study of photo optical imaging (POI), with clinical examination (CE), disease activity score at 28 joints (DAS28)-erythrocyte sedimentation rate (ESR), and musculoskeletal ultrasonography (US) in healthy subjects and patients with rheumatoid arthritis (RA) or osteoarthritis (OA).Methods.There were 688 PIP joints of both hands examined in 87 subjects (38 RA, 21 OA, 28 healthy) by Lightscan and compared with CE for clinically swollen and tender joints, DAS28-ESR (only RA), and US.Results.With US as reference, POI had a sensitivity of 74% and a specificity of 93%. In the receiver-operating curve (ROC) analysis, the Lightscan showed a higher sensitivity and specificity [area under the curve (AUC) 0.879] for the distinction of healthy subjects versus patients (OA, RA) than US in greyscale (GSUS; AUC 0.797) and power Doppler (PDUS; AUC 0.67). POI correlated significantly with GSUS (r 0.473, p < 0.01) and PDUS (r 0.486, p < 0.01). The agreement rates between POI and GSUS were up to 79%, between POI and PDUS up to 92%, and between POI and CE up to 66%. POI did not correlate with DAS28-ESR.Conclusion.The Lightscan is a new technology offering sensitive imaging detection of inflammatory changes in subjects with RA and OA with PIP arthritis. POI was more sensitive than CE and correlated significantly to GSUS and PDUS, while presenting a higher sensitivity and specificity for the detection of healthy subjects versus patients (RA, OA) based on the ROC analysis.
An Observational Study of Gout Prevalence and Quality of Care in a National Australian General Practice Population
Authors: Robinson Philip C. , Taylor William J. , Dalbeth Nicola 
Published: August 2015

Objective.The central strategy for effective gout management is longterm urate-lowering therapy to maintain the serum urate at a level below 0.36 mmol/l. We sought to determine the prevalence of gout and the quality of care in a national Australian general practice population.Methods.Data were from general practice point-of-care electronic records over a 5-year period (n = 1,479,449). Information was collected on patients with gout according to a validated definition. All patients who visited the same general practices over the study period formed the denominator group. We determined the estimated prevalence of gout, the frequency of allopurinol prescription, and serum urate testing, and the percentage of patients achieving a target serum urate level.Results.The crude prevalence of gout in this general practice population was 1.54% (95% CI 1.52–1.56). Prevalence in men was 2.67% and in women 0.53%. Prevalence increased with age in both men and women (4.90%, 95% CI 4.82–4.99, in men > 65 yrs). Allopurinol was prescribed to 57% of patients with gout during the 5 years of the study. Only 55% of patients with gout had their serum urate tested at any time during the 5-year study period. A target serum urate concentration of < 0.36 mmol/l at any time during the 5-year study period was documented in 22.4% of all people with gout.Conclusion.Gout is managed poorly in Australian primary care, with low levels of allopurinol prescribing and serum urate testing. Collectively, these factors probably contribute to low achievement of serum urate targets.
A Competence-Oriented Approach to Subject-Matter Didactics for Software Engineering
Authors: Sedelmaier Yvonne , Landes Dieter 
Published: August 2015

Instructors not only in higher education are regularly faced with the problem that they need to develop a new course or adapt an existing one to changed requirements. This is especially true for topics related to information technology (IT) due to the fast technological progress. Instructors, however, are not prepared really well for this task since they typically have a professional and educational background in areas different from pedagogy. Therefore, some sort of methodological framework to support the systematic development and refinement of courses would be highly appreciated.
This paper presents such a model, called Competence-Oriented Subject-Matter Didactics. This didactical theory builds upon several concepts from general didactics, most notably Klafki’s Didactic Analysis, and combines and extends these concepts. As a proof of concept, Competence-Oriented Subject-Matter Didactics is applied to the refinement of an introductory course on information systems. This case study indicates, among other things, that this theoretical model has the potential to be applicable for course (re-)design in other domains beyond IT as well.
The Raf Kinase Inhibitor Sorafenib Inhibits JAK–STAT Signal Transduction in Human Immune Cells
Authors: Martin del Campo Sara E. , Levine Kala M. , Mundy-Bosse Bethany L. , Grignol Valerie P. , Fairchild Ene T. , Campbell Amanda R. , Trikha Prashant , Mace Thomas A. , Paul Bonnie K. , Jaime-Ramirez Alena Cristina , Markowitz Joseph , Kondadasula Sri Vidya , Guenterberg Kristan D. , McClory Susan , Karpa Volodymyr I. , Pan Xueliang , Olencki Thomas E. , Monk J. Paul , Mortazavi Amir , Tridandapani Susheela , Lesinski Gregory B. , Byrd John C. , Caligiuri Michael A. , Shah Manisha H. , Carson William E. 
Published: August 2015

AbstractSorafenib is an oral multikinase inhibitor that was originally developed as a Raf kinase inhibitor. We hypothesized that sorafenib would also have inhibitory effects on cytokine signaling pathways in immune cells. PBMCs from normal donors were treated with varying concentrations of sorafenib and stimulated with IFN-α or IL-2. Phosphorylation of STAT1 and STAT5 was measured by flow cytometry and confirmed by immunoblot analysis. Changes in IFN-α– and IL-2–stimulated gene expression were measured by quantitative PCR, and changes in cytokine production were evaluated by ELISA. Cryopreserved PBMCs were obtained from cancer patients before and after receiving 400 mg sorafenib twice daily. Patient PBMCs were thawed, stimulated with IL-2 or IFN-α, and evaluated for phosphorylation of STAT1 and STAT5. Pretreatment of PBMCs with 10 μM sorafenib decreased STAT1 and STAT5 phosphorylation after treatment with IFN-α or IL-2. This inhibitory effect was observed in PBMCs from healthy donors over a range of concentrations of sorafenib (5–20 μM), IL-2 (2–24 nM), and IFN-α (101–106 U/ml). This effect was observed in immune cell subsets, including T cells, B cells, NK cells, regulatory T cells, and myeloid-derived suppressor cells. Pretreatment with sorafenib also inhibited PBMC expression of IFN-α– and IL-2–regulated genes and inhibited NK cell production of IFN-γ, RANTES, MIP1-α, and MIG in response to IFN-α stimulation. PBMCs from patients receiving sorafenib therapy showed decreased responsiveness to IL-2 and IFN-α treatment. Sorafenib is a Raf kinase inhibitor that could have off-target effects on cytokine-induced signal transduction in immune effector cells.
Endothelial LSP1 Modulates Extravascular Neutrophil Chemotaxis by Regulating Nonhematopoietic Vascular PECAM-1 Expression
Authors: Hossain Mokarram , Qadri Syed M. , Xu Najia , Su Yang , Cayabyab Francisco S. , Heit Bryan , Liu Lixin 
Published: August 2015

Abstract
During inflammation, leukocyte–endothelial cell interactions generate molecular signals that regulate cell functions. The Ca2+- and F-actin–binding leukocyte-specific protein 1 (LSP1) expressed in leukocytes and nonhematopoietic endothelial cells is pivotal in regulating microvascular permeability and leukocyte recruitment. However, cell-specific function of LSP1 during leukocyte recruitment remains elusive. Using intravital microscopy of cremasteric microvasculature of chimeric LSP1-deficient mice, we show that not neutrophil but endothelial LSP1 regulates neutrophil transendothelial migration and extravascular directionality without affecting the speed of neutrophil migration in tissue in response to CXCL2 chemokine gradient. The expression of PECAM-1–sensitive α6β1 integrins on the surface of transmigrated neutrophils was blunted in mice deficient in endothelial LSP1. Functional blocking studies in vivo and in vitro elucidated that α6β1 integrins orchestrated extravascular directionality but not the speed of neutrophil migration. In LSP1-deficient mice, PECAM-1 expression was reduced in endothelial cells, but not in neutrophils. Similarly, LSP1-targeted small interfering RNA silencing in murine endothelial cells mitigated mRNA and protein expression of PECAM-1, but not ICAM-1 or VCAM-1. Overexpression of LSP1 in endothelial cells upregulated PECAM-1 expression. Furthermore, the expression of transcription factor GATA-2 that regulates endothelial PECAM-1 expression was blunted in LSP1-deficient or LSP1-silenced endothelial cells. The present study unravels endothelial LSP1 as a novel cell-specific regulator of integrin α6β1-dependent neutrophil extravascular chemotactic function in vivo, effective through GATA-2–dependent transcriptional regulation of endothelial PECAM-1 expression.
Th Cell Diversity in Experimental Autoimmune Encephalomyelitis and Multiple Sclerosis
Authors: Carbajal Kevin S. , Mironova Yevgeniya , Ulrich-Lewis Justin T. , Kulkarni Deven , Grifka-Walk Heather M. , Huber Amanda K. , Shrager Peter , Giger Roman J. , Segal Benjamin M. 
Published: August 2015

Abstract
Multiple sclerosis (MS) is believed to be initiated by myelin-reactive CD4+ Th cells. IL-12–polarized Th1 cells, IL-23–polarized Th17 cells, and Th17 cells that acquire Th1 characteristics were each implicated in autoimmune pathogenesis. It is debated whether Th cells that can drive the development of demyelinating lesions are phenotypically diverse or arise from a single lineage. In the current study, we assessed the requirement of IL-12 or IL-23 stimulation, as well as Th plasticity, for the differentiation of T cells capable of inducing CNS axon damage. We found that stable murine Th1 and Th17 cells independently transfer experimental autoimmune encephalomyelitis (widely used as an animal model of MS) in the absence of IL-23 and IL-12, respectively. Plastic Th17 cells are particularly potent mediators of demyelination and axonopathy. In parallel studies, we identified MS patients who consistently mount either IFN-γ– or IL-17–skewed responses to myelin basic protein over the course of a year. Brain magnetic resonance imaging revealed that patients with mixed IFN-γ and IL-17 responses have relatively high T1 lesion burden, a measure of permanent axon damage. Our data challenge the dogma that IL-23 and Th17 plasticity are universally required for the development of experimental autoimmune encephalomyelitis. This study definitively demonstrates that autoimmune demyelinating disease can be driven by distinct Th-polarizing factors and effector subsets, underscoring the importance of a customized approach to the pharmaceutical management of MS.
Incidence and Potential Significance of Internal Mammary Lymphadenopathy on Computed Tomography in Patients with a Diagnosis of Primary Breast Cancer
Authors: Savaridas Sarah L. , Spratt Jonathan D. , Cox Julie 
Published: August 2015

Introduction The importance of internal mammary nodes (IMNs) in the staging and treatment of breast cancer patients is controversial. Methods A retrospective cohort of patients diagnosed with primary breast cancer over a 4-year period (January 2009 to December 2012) was assessed. The number and size of any IMNs visible on spiral computed tomography (CT) were recorded. Results A total of 830 patients were diagnosed with primary breast cancer within the identified time frame, of which 150 patients met the inclusion criteria. Of these 42% (63) had IMNs present, although the majority were small (<5 mm). However, 16% (25) had larger nodes, greater than 5 mm in short axis, present on CT. Significantly more patients with the presence of large (>5 mm) IMNs had more advanced disease with CT evidence of other distant spread. Conclusion We have demonstrated that IMNs are present in a substantial number of our primary breast cancer patients. We suggest that further histological research is required to establish reliable CT size criterion for pathological IMNs. In addition, routine imaging of the IM chain, as well as axilla, should be considered in the staging of breast cancer.
Multidisciplinary Prognostication Using the Palliative Prognostic Score in an Australian Cancer Center
Authors: Mendis Ruwani , Soo Wee-Kheng , Zannino Diana , Michael Natasha , Spruyt Odette 
Published: August 2015

Context Accurate prognostication is important in oncology and palliative care. A multidisciplinary approach to prognostication provides a novel approach, but its accuracy and application is poorly researched. In this study, we describe and analyze our experience of multidisciplinary prognostication in palliative care patients with cancer. Objectives To assess our accuracy of prognostication using multidisciplinary team prediction of survival (MTPS) alone and within the Palliative Prognostic (PaP) Score. Methods This retrospective study included all new patients referred to a palliative care consultation service in a tertiary cancer center between January 2010 and December 2011. Initial assessment data for 421 inpatients and 223 outpatients were analyzed according to inpatient and outpatient groups to evaluate the accuracy of prognostication using MTPS alone and within the PaP score (MTPS-PaP) and their correlation with overall survival. Results Inpatients with MTPS-PaP group A, B, and C had a median survival of 10.9, 3.4, and 0.7 weeks, respectively, and a 30-day survival probability of 81%, 40%, and 10%, respectively. Outpatients with MTPS-PaP group A and B had a median survival of 17.3 and 5.1 weeks, respectively, and a 30-day survival probability of 94% and 50%, respectively. MTPS overestimated survival by a factor of 1.5 for inpatients and 1.2 for outpatients. The MTPS-PaP score correlated better than MTPS alone with overall survival. Conclusion This study suggests that a multidisciplinary team approach to prognostication within routine clinical practice is possible and may substitute for single clinician prediction of survival within the PaP score without detracting from its accuracy. Multidisciplinary team prognostication can assist treating teams to recognize and articulate prognosis, facilitate treatment decisions, and plan end-of-life care appropriately. PaP was less useful in the outpatient setting, given the longer survival interval of the outpatient palliative care patient group.
Characteristics and survival for HIV‐associated multicentric Castleman disease in Malawi
Authors: Gopal Satish , Liomba N George , Montgomery Nathan D , Moses Agnes , Kaimila Bongani , Nyasosela Richard , Chikasema Maria , Dhungel Bal M , Kampani Coxcilly , Sanders Marcia K , Krysiak Robert , Dittmer Dirk P , Fedoriw Yuri 
Published: August 2015

IntroductionClinical reports of multicentric Castleman disease (MCD) from sub‐Saharan Africa (SSA) are scarce despite high prevalence of HIV and Kaposi sarcoma‐associated herpesvirus (KSHV). Our objective is to describe characteristics and survival for HIV‐associated MCD patients in Malawi. To our knowledge, this is the first HIV‐associated MCD case series from the region.MethodsWe describe HIV‐positive patients with MCD in Lilongwe, and compare them to HIV‐associated lymph node Kaposi sarcoma (KS) and non‐Hodgkin lymphoma (NHL) patients treated at our centre. All patients were enrolled into a prospective longitudinal cohort study at a national teaching hospital and cancer referral centre serving half of Malawi's 16 million people. We included adult patients≥18 years of age with HIV‐associated MCD (n=6), lymph node KS (n=5) or NHL (n=31) enrolled between 1 June 2013 and 31 January 2015.Results and discussionMCD patients had a median age of 42.4 years (range 37.2–51.8). All had diffuse lymphadenopathy and five had hepatosplenomegaly. Concurrent KS was present for one MCD patient, and four had performance status ≥3. MCD patients had lower median haemoglobin (6.4 g/dL, range 3.6–9.3) than KS (11.0 g/dL, range 9.1–12.0, p=0.011) or NHL (11.2 g/dL, range 4.5–15.1, p=0.0007). Median serum albumin was also lower for MCD (2.1 g/dL, range 1.7–3.2) than KS (3.7 g/dL, range 3.2–3.9, p=0.013) or NHL (3.4 g/dL, range 1.8–4.8, p=0.003). All six MCD patients were on antiretroviral therapy (ART) with median CD4 count 208 cells/µL (range 108–1146), and all with HIV RNA <400 copies/mL. Most KS and NHL patients were also on ART, although ART duration was longer for MCD (56.4 months, range 18.2–105.3) than KS (14.2 months, range 6.8–21.9, p=0.039) or NHL (13.8 months, range 0.2–98.8, p=0.017). Survival was poorer for MCD patients than lymph node KS or NHL.ConclusionsHIV‐associated MCD occurs in Malawi, is diagnosed late and is associated with high mortality. Improvements in awareness, diagnostic facilities, treatment and supportive care are needed to address this likely under‐recognized public health problem in SSA.
Probabilistic seismic performance estimation through surrogate model and unbiased multi‐fidelity Monte Carlo predictor
Authors: Gao Xiaoshu , Iyama Jun , Itoi Tatsuya 
Published: August 2024

AbstractThis study introduces an approach for probabilistic seismic performance estimation, which focuses on the probability of intensity measures exceeding a specified value based on engineering demand parameters. Conventional methods face challenges owing to the increase in computational costs associated with the uncertainties in earthquake scenarios. To address this, we use high‐fidelity (HF) and low‐fidelity (LF) model data to develop a multilevel hierarchy of surrogate models, which improves the simulation‐based probabilistic estimation. However, designing a reliable LF model and ensuring the accuracy of the surrogate model hierarchy remains challenging. Herein, we present a multi‐fidelity Monte Carlo (MFMC) predictor combined with a conventional surrogate model to improve probabilistic seismic performance estimation, thereby leveraging LF model efficiency and HF data accuracy for unbiased results. We addressed the challenge of constructing a suitable LF model by using a surrogate model trained from limited HF data. The MFMC predictor improves the accuracy of probabilistic analysis than the surrogate models trained from limited HF data. Further, the automatic relevance determination method is introduced to select the most appropriate inputs for the surrogate model. A case study featuring a special moment‐resistant frame, subject to uncertainties from both ground motion and structural properties, illustrates the efficiency of the method. A LF model is developed using the Kriging method, followed by the construction of the MFMC predictor for probabilistic analysis, thereby leveraging both limited HF and numerous LF data. Comparing the exceedance probability curves obtained from the MFMC predictor with those from direct Monte Carlo simulations and conventional Kriging showed that our proposed method offers a promising tool for probabilistic seismic performance estimation under uncertainty.