tbuckley/cabot-search huggingface dataset:
Predictors of productivity loss in early rheumatoid arthritis: a 5 year follow up study
Authors: K Puolakka
Journal: Annals of the Rheumatic Diseases (2004)

<b>Objective:</b> To explore baseline risk factors for productivity loss and work disability over 5 years in patients with early, active RA. <b>Patients and methods:</b> In the FIN-RACo trial, 195 patients with recent onset RA were randomised to receive either a combination of DMARDs with prednisolone or a single DMARD for 2 years. At baseline, 162 patients were working or available for work. After 5 years' follow up, data on sick leave and retirement were obtained from social insurance registers or case records. The cumulative duration of sick leaves and RA related disability pensions was counted for each patient. To analyse predictors of productivity loss, the patients were divided into four groups according to duration of work disability per patient year. <b>Results:</b> Patient's and physician's global assessment of RA severity ⩾50 and HAQ score ⩾1.0 were risk factors for extension of productivity loss (OR (95% (CI) 1.77 (1.00 to 3.16), 1.85 (1.03 to 3.32), and 1.78 (1.01 to 3.14), respectively). Additional risk factors were low education level (2.40 (1.18 to 4.88)) and older age (1.03 (1.00 to 1.06)); combination treatment was a protective factor (0.59 (0.35 to 0.99)). <b>Conclusion:</b> At baseline, the risk of future productivity loss is best predicted by education level, age, global assessments of RA severity, and HAQ score.
Prospective evaluation of ursodeoxycholic acid withdrawal in patients with primary sclerosing cholangitis
Authors: Ewa Wunsch, Jocelyn Trottier, Malgorzata Milkiewicz, Joanna Raszeja-Wyszomirska, Gideon M. Hirschfield, Olivier Barbier, Piotr Milkiewicz
Journal: Hepatology (2014)

Ursodeoxycholic acid (UDCA) is no longer recommended for management of adult patients with primary sclerosing cholangitis (PSC). We undertook a prospective evaluation of UDCA withdrawal in a group of consecutive patients with PSC. Twenty six patients, all treated with UDCA (dose range: 10-15 mg/kg/day) were included. Paired blood samples for liver biochemistry, bile acids, and fibroblast growth factor 19 (FGF19) were collected before UDCA withdrawal and 3 months later. Liquid chromatography/tandem mass spectrometry was used for quantification of 29 plasma bile acid metabolites. Pruritus and health-related quality of life (HRQoL) were assessed with a 10-point numeric rating scale, the Medical Outcomes Study Short Form-36 (SF-36), and PBC-40 questionnaires. UDCA withdrawal resulted in a significant deterioration in liver biochemistry (increase of alkaline phosphatase of 75.6%; P<0.0001; gamma-glutamyl transpeptidase of 117.9%, P<0.0001; bilirubin of 50.0%, P<0.001; alanine aminotransferase of 63.9%, P<0.005; and aspartate aminotransferase of 45.0%, P<0.005) and increase of Mayo Risk Score for PSC (change from baseline of +0.5 point; P<0.003). Bile acid analysis revealed a significant decrease in lithocholic acid and its derivatives after UDCA withdrawal, but no effect on concentrations of primary bile acids aside from an increased accumulation of their taurine conjugates. After UDCA removal cholestatic parameters, taurine species of cholic acid and chenodeoxycholic acid correlated with serum FGF19 levels. No significant effect on HRQoL after UDCA withdrawal was observed; however, 42% of patients reported a deterioration in their pruritus. At 3 months, discontinuation of UDCA in patients with PSC causes significant deterioration in liver biochemistry and influences concentrations of bile acid metabolites. A proportion of patients report increased pruritus, but other short-term markers of quality of life are unaffected.
A cell surface antigen of the mouse related to xenotropic MuLv defined by naturally occurring antibody and monoclonal antibody. Relation to Gix G(rada1), G(aksl2) systems of MuLV-related antigens.
Authors: Y Obata, E Stockert, A B DeLeo, P V O'Donnell, H W Snyder, L J Old
Journal: The Journal of Experimental Medicine (1981)

A new cell surface antigen of the mouse related to xenotropic murine leukemia virus (MuLV) is described. The antigen, designated G(erld), is defined by cytotoxic tests with the B6-x-ray-induced ERLD and naturally occurring antibody. G(erld) is distinct from all previously defined cell surface antigens. Monoclonal antibody with the same specificity has been developed. Inbred mouse strains are classified as G(erld)+ or G(erld)- according to the presence of absence of the antigen on lymphoid cells. G(erld)+ strains differ with regard to quantitative expression of G(erld) on normal thymocytes. The emergence of G(erld)+ tumors in G(erld)- strains indicates the presence of genes coding for the antigen even in strains not normally expressing the antigen. G(erld) has the characteristic of a differentiation antigen in normal mice. In G(erld)+ strains, high levels of the antigen are found on thymocytes with lower levels being detected on cells of spleen, lymph nodes and bone marrow. No G(erld) was detected in brain or kidney or on erythrocytes. The segregation ratios for G(erld) expression on thymocytes in backcross and F2 mice of crosses between G(erld)+ (B6, 129, and B6-Gix+) and G(erld)- (BALB/c) strains suggest that G(erld) expression is controlled by a single locus in B6, by two unlinked loci in 129, and by three unlinked loci in B6-Gix+ mice. Induction of the antigen by MuLV infection of permissive cells in vitro indicates that G(erld) is closely related to xenotropic and dualtropic MuLV; all xenotropic and dualtropic MuLV tested induced the antigen, whereas the majority of ecotropic and the two amphotropic MuLV failed to do so. As dualtropic MuLV are thought to be recombinants between ecotropic and xenotropic MuLV sequences, G(erld) coding by dualtropic MuLV may signify the contribution of the xenotropic part in the recombinational event. Serological and biochemical characterization indicates that G(erld) is related to the gp 70 component of the MuLV envelope. The relation of G(erld) to the previously defined gp 70-related cell surface antigens (Gix, G(rada), and G(aksl2) is discussed, particularly with regard to their characteristics as differentiation antigens, the genetic origin of dualtropic MuLV, and the leukemogenicity of MuLV.
Psychological Treatment of Chronic Pain
Authors: Robert D. Kerns, John Sellinger, Burel R. Goodin
Journal: Annual Review of Clinical Psychology (2011)

Psychological treatment has emerged as a common component of a multidimensional and interdisciplinary plan of pain care for many persons with persistent pain. Treatments are informed by a biopsychosocial model of pain and a long history of psychological research that has identified the central role of behavioral, cognitive, and emotional factors that are believed to contribute to the perpetuation, if not the development, of chronic pain and pain-related disability and emotional distress. Empirically supported self-regulatory, behavioral, cognitive-behavioral, and acceptance and commitment interventions are reviewed, and current and future interventions are highlighted. Important issues related to individual differences and disparities in the experience of pain and pain treatment are discussed. In particular, race and ethnicity are considered, and special considerations for the management of pain in children and older adults are discussed.
CXCR6 Upregulation Contributes to a Proinflammatory Tumor Microenvironment That Drives Metastasis and Poor Patient Outcomes in Hepatocellular Carcinoma
Authors: Qiang Gao, Ying-Jun Zhao, Xiao-Ying Wang, Shuang-Jian Qiu, Ying-Hong Shi, Jian Sun, Yong Yi, Jie-Yi Shi, Guo-Ming Shi, Zhen-Bin Ding, Yong-Sheng Xiao, Zhong-Hua Zhao, Jian Zhou, Xiang-Huo He, Jia Fan
Journal: Cancer Research (2012)

CXC chemokines and their cognate receptors have been implicated widely in cancer pathogenesis. In this study, we report a critical causal relationship between CXCR6 expression and tumorigenesis in the setting of human hepatocellular carcinoma (HCC). Among the CXC chemokine receptors, only CXCR6 was detected in all the hepatoma cell lines studied. Moreover, in HCC tissue, CXCR6 expression was significantly higher than in noncancerous liver tissues. Reduction of CXCR6 or its ligand CXCL16 in cancer cells reduced cell invasion in vitro and tumor growth, angiogenesis, and metastases in vivo. Importantly, loss of CXCR6 led to reduced Gr-1+ neutrophil infiltration and decreased neoangiogenesis in hepatoma xenografts via inhibition of proinflammatory cytokine production. Clinically, high expression of CXCR6 was an independent predictor of increased recurrence and poor survival in HCCs. Human HCC samples expressing high levels of CXCR6 also contained an increased number of CD66b+ neutrophils and microvessels, and the combination of CXCR6 and neutrophils was a superior predictor of recurrence and survival than either marker used alone. Together, our findings suggest that elevated expression of CXCR6 promotes HCC invasiveness and a protumor inflammatory environment and is associated with poor patient outcome. These results support the concept that inhibition of the CXCR6-CXCL16 pathway may improve prognosis after HCC treatment.
Biosynthesis of pro-C3, a precursor of the third component of complement.
Authors: V Brade, R E Hall, H R Colten
Journal: The Journal of Experimental Medicine (1977)

A precusor of the third component of complement, pro-C3, was detected in studies of cell-free synthesis and intracellularly in homogenates of liver tissue cultures. The molecular weight of pro-C3 was indistinguishable from that of intact native C3 secreted in vitro by liver or peritoneal macrophages, but its structure was different. Pro-C3 is a single polypeptide chain, whereas C3 secreted by cells in culture consists of two polypeptide chains (mol wt 120,000 and 76,000) linked by disulfide bonds.
Identification and Characterization of a Novel Melanoma Tumor Suppressor Gene on Human Chromosome 6q21
Authors: Jackie Mei-Wah Fung, Ross Smith, Melissa A. Brown, Sze Hang Lau, Dan Xie, George K. Lau, Xin-Yuan Guan
Journal: Clinical Cancer Research (2009)

Abstract Purpose: By characterizing a complex chromosome rearrangement involving 6q and 17p in melanoma cell line UACC-930, we isolated a candidate tumor suppressor gene at 6q21, named prenyl diphosphate synthase subunit 2 (PDSS2), which was interrupted by an inversion breakpoint. The purpose of this study was to determine the tumor-suppressive potential of PDSS2 in the development of melanoma. Experimental Design: To isolate the rearranged 6q in UACC-930 cells, a bacterial artificial chromosome clone (RP1-67A8) covering the breakpoint at 6q21 was digested with HindIII and each DNA fragment was used as the probe for the breakpoint in Southern blotting. The HindIII fragment probe covering the breakpoint was then used to screen an EcoRI-digested DNA library generated from UACC-930. To characterize the tumor-suppressive potential of PDSS2, PDSS2 was stably transfected into a highly tumorigenic melanoma cell line, UACC-903. The tumor-suppressive function of PDSS2 was shown by both in vitro and in vivo assays. The differential expression of PDSS2 in benign nevi and primary melanoma samples was also studied. Results: Down-regulation of PDSS2 was observed in 59 of 87 (67.8%) primary melanomas, which was significantly higher than that in benign nevi (7 of 66, 10.6%; P &amp;lt; 0.001). In addition, an overexpression of the PDSS2 in UACC-903 cells could inhibit tumor cell growth, decrease the colony-forming ability in soft agar, and totally abrogate the tumorigenicity of UACC-903 in nude mice. Conclusions: Our results support the proposal that PDSS2 is a novel tumor suppressor gene that plays an important role in the development of malignant melanoma.
Adeno-associated virus–targeted disruption of the CFTR gene in cloned ferrets
Authors: Xingshen Sun, Ziying Yan, Yaling Yi, Ziyi Li, Diana Lei, Christopher S. Rogers, Juan Chen, Yulong Zhang, Michael J. Welsh, Gregory H. Leno, John F. Engelhardt
Journal: Journal of Clinical Investigation (2008)

Somatic cell gene targeting combined with nuclear transfer cloning presents tremendous potential for the creation of new, large-animal models of human diseases. Mouse disease models often fail to reproduce human phenotypes, underscoring the need for the generation and study of alternative disease models. Mice deficient for CFTR have been poor models for cystic fibrosis (CF), lacking many aspects of human CF lung disease. In this study, we describe the production of a CFTR gene-deficient model in the domestic ferret using recombinant adeno-associated virus-mediated gene targeting in fibroblasts, followed by nuclear transfer cloning. As part of this approach, we developed a somatic cell rejuvenation protocol using serial nuclear transfer to produce live CFTR-deficient clones from senescent gene-targeted fibroblasts. We transferred 472 reconstructed embryos into 11 recipient jills and obtained 8 healthy male ferret clones heterozygous for a disruption in exon 10 of the CFTR gene. To our knowledge, this study represents the first description of genetically engineered ferrets and describes an approach that may be of substantial utility in modeling not only CF, but also other genetic diseases.
Trends in Career Choice by US Medical School Graduates
Authors: Dale A. Newton
Journal: JAMA (2003)

Trends in career choice among specialties have varied greatly. Most notable is the recent decrease in the percentage of US medical student graduates choosing a primary care career, which has important implications for the US physician workforce.To review temporal trends in career choice by graduates of allopathic US medical schools, focusing on US medical doctors entering residencies since 1987.Three databases, the Association of American Medical Colleges Graduation Questionnaire (AAMC GQ), the National Resident Matching Program, and the national Graduate Medical Education census, were used to review temporal trends in the number of US medical doctors entering residencies in primary care, general or subspecialty surgical, and non-primary care and nonsurgical specialties from 1987 to 2002.In 1987, 49.2% of all medical school graduates matched to one of the generalist residencies (internal medicine, pediatrics, or family medicine). The percentage of students matching to primary care specialties declined in the early 1990s, peaked at 53.2% in 1998, and declined to 44.2% in 2002. Concurrent with the latter decline, AAMC GQ data showed a decrease in medical student interest in primary care careers (35.6% in 1999 to 21.5% in 2002). The total percentage of US medical doctors matching to general or subspecialty surgical residencies remained stable at 11% to 12% from 1987 to 2002. During this same period, emergency medicine and plastic surgery increased as a match choice, while anesthesiology, pathology, and psychiatry were more variable over time.Distribution of medical students' career choices among specialties varied considerably from 1987 to 2002. The debate will continue regarding the appropriate specialty mix within the physician workforce.
Cross-Sectional and Longitudinal Relationships Between Cerebrospinal Fluid Biomarkers and Cognitive Function in People Without Cognitive Impairment From Across the Adult Life Span
Authors: Ge Li, Steven P. Millard, Elaine R. Peskind, Jing Zhang, Chang-En Yu, James B. Leverenz, Cynthia Mayer, Jane S. Shofer, Murray A. Raskind, Joseph F. Quinn, Douglas R. Galasko, Thomas J. Montine
Journal: JAMA Neurology (2014)

<h3>Importance</h3> Age-related cognitive decline among older individuals with normal cognition is a complex trait that potentially derives from processes of aging, inherited vulnerabilities, environmental factors, and common latent diseases that can progress to cause dementia, such as Alzheimer disease and vascular brain injury. <h3>Objective</h3> To use cerebrospinal fluid (CSF) biomarkers to gain insight into this complex trait. <h3>Design, Setting, and Participants</h3> Secondary analyses of an academic multicenter cross-sectional (n = 315) and longitudinal (n = 158) study of 5 neuropsychological tests (Immediate Recall, Delayed Recall, Trail Making Test Parts A and B, and Category Fluency) in cognitively normal individuals aged 21 to 100 years. <h3>Main Outcomes and Measures</h3> To investigate the association of these cognitive function test results with age, sex, educational level, inheritance of the ε4 allele of the apolipoprotein E gene, and CSF concentrations of β-amyloid 42 (Aβ42) and tau (biomarkers of Alzheimer disease) as well as F<sub>2</sub>-isoprostanes (measures of free radical injury). <h3>Results</h3> Age and educational level were broadly predictive of cross-sectional cognitive performance; of the genetic and CSF measures, only greater CSF F<sub>2</sub>-isoprostane concentration was significantly associated with poorer executive function (adjusted<i>R</i><sup>2</sup>≤0.31). Longitudinal measures of cognitive abilities, except Category Fluency, also were associated broadly with age; of the genetic and CSF measures, only lower baseline CSF Aβ42 concentration was associated with longitudinal measures of immediate and delayed recall (marginal<i>R</i><sup>2</sup>≤0.31). <h3>Conclusions and Relevance</h3> Our results suggest that age and educational level accounted for a substantial minority of variance in cross-sectional or longitudinal cognitive test performance in this large group of cognitively normal adults. Latent Alzheimer disease and other diseases that produce free radical injury, such as vascular brain injury, accounted for a small amount of variation in cognitive test performance across the adult human life span. Additional genetic and environmental factors likely contribute substantially to age-related cognitive decline.
Role of Calcium-Activated Neutral Protease (Calpain) in Cell Death in Cultured Neonatal Rat Cardiomyocytes During Metabolic Inhibition
Authors: Douwe E. Atsma, E.M. Lars Bastiaanse, Anastazia Jerzewski, Lizet J.M. Van der Valk, Arnoud Van der Laarse
Journal: Circulation Research (1995)

Abstract Calcium-activated neutral protease (CANP), also known as calpain, has been implicated in the development of cell death in ischemic hearts. CANP is thought to be activated by the calcium overload that develops during ischemia. We studied the involvement of CANP in cell death in cultured neonatal rat cardiomyocytes during metabolic inhibition (5 mmol/L NaCN+10 mmol/L 2-deoxyglucose). First, we isolated CANP using ion exchange and affinity chromatography. Then the efficacy of the CANP inhibitors calpain I inhibitor, leupeptin, and E64 to inhibit isolated CANP activity was tested with the use of fluorescently labeled β-casein as a substrate. The IC 50 for the inhibitors was between 2.1 and 56 μmol/L. Uptake of the inhibitors by intact cells was assessed with the use of 99m Tc-radiolabeled inhibitors. The calculated intracellular inhibitor concentrations were sufficiently high to yield substantial inhibition of intracellular CANP activity. Intracellular CANP activity was measured directly with the use of the cell-permeant fluorogenic CANP-specific substrate N -succinyl-Leu-Leu-Val-Tyr-7-amido-4-methyl-coumarin. During metabolic inhibition, intracellular CANP activity was increased compared with control incubation. The time course of CANP activation was compatible with that of the rise in [Ca 2+ ] i , as measured by fura 2 and digital imaging fluorescence microscopy. Calpain I inhibitor and leupeptin inhibited intracellular CANP activity both during metabolic inhibition and control incubation, whereas E64 did not. Despite their substantial inhibition of intracellular CANP activity, calpain I inhibitor and leupeptin did not attenuate cell death during metabolic inhibition. We therefore conclude that intracellular CANP in cardiomyocytes is activated during metabolic inhibition, but it does not play a major role in the development of cell death.
Effect of bariatric surgery on the inflammatory response to monosodium urate crystals: a prospective study
Authors: Nicola Dalbeth, Bregina Pool, Shelley Yip, Jillian Cornish, Rinki Murphy
Journal: Annals of the Rheumatic Diseases (2013)

The association of obesity with the development of gout has been attributed to hyperuricaemia.1 ,2 However, in patients with poorly controlled gout, weight loss leads to profound suppression of gout flares, despite a relatively small reduction in urate concentrations.3 Monosodium urate (MSU) crystals are frequently identified in asymptomatic, uninflamed joints in patients with gout,4 suggesting that local or systemic factors regulate the inflammatory response to intra-articular crystals. Since weight loss is associated with reduced chronic inflammation,5 we hypothesised that weight loss influences the presentation of gout through regulation of inflammatory responses to MSU crystals.

Twenty patients with morbid obesity (body mass index ≥35 kg/m2) and type 2 diabetes, with no history of gout, were prospectively recruited from two public hospitals in Auckland, New Zealand. The Northern X Ethics Committee approved the study and all patients provided …
Hyperdiploidy Plus Nonamplified <i>MYCN</i> Confers a Favorable Prognosis in Children 12 to 18 Months Old With Disseminated Neuroblastoma: A Pediatric Oncology Group Study
Authors: Rani E. George, Wendy B. London, Susan L. Cohn, John M. Maris, Cynthia Kretschmar, Lisa Diller, Garrett M. Brodeur, Robert P. Castleberry, A. Thomas Look
Journal: Journal of Clinical Oncology (2005)

Purpose To determine predictive strength of tumor cell ploidy and MYCN gene amplification on survival of children older than 12 months with disseminated neuroblastoma (NB). Patients and Methods Of 648 children with stage D NB enrolled onto the Pediatric Oncology Group NB Biology Study 9047 (1990-2000), 560 children were assessable for ploidy and MYCN amplification. Treatment of patients older than 12 months varied; most receiving high-dose chemotherapy with stem-cell rescue. Infants received standard chemotherapy, depending on MYCN status and ploidy. Results Among stage D MYCN-amplified patients, 4-year event-free survival (EFS) ± SE had no prognostic significance for tumor cell ploidy for patients either younger than 12 months or ≥ 12 months old. However, among stage D nonamplified-MYCN patients, 4-year EFS for those with tumor hyperdiploidy (DNA index [DI] &gt; 1) was clearly superior to those with diploidy (DI ≤ 1): younger than 12 months, 83.7% ± 4.4% (n = 87) versus 46.2% ± 13.8% (n = 13; P = .0003); and for 12- to 24-month-old children, 72.7% ± 10.2% (n = 22) versus 26.7% ± 13.2% (n = 16; P = .0092). Further analysis suggested better prognoses in the 12- to 18-month-old subgroup with hyperdiploid tumors (4-year EFS, 92.9% ± 7.2%) compared with the 19- to 24-month-old subgroup (4-year EFS, 37.5% ± 21.0%; P = .0037). In children older than 24 months, outcome was dire (&lt; 20% long-term survival), regardless of ploidy or MYCN status. Conclusion Children 12 to 18 months old with metastatic NB had favorable outcomes with high-dose therapy if their tumors were hyperdiploid and lacked MYCN amplification. This subgroup may respond well to contemporary chemotherapy, and could be spared intensive myeloablative therapy with stem-cell rescue.
Male skin and ingredients relevant to male skin care
Authors: Z.D. Draelos
Journal: British Journal of Dermatology (2012)

Male skin care needs are heavily influenced by the need to remove facial hair on a regular basis. Facial skin issues associated with poor hair removal approaches are common and include razor burn and irritation. This paper evaluates current research on shaving technology and how careful ingredient selection can contribute to male skin health. The importance of maintaining hair softness during the shave and restoring facial hydration post‐shave is discussed. Data are presented on how post‐shave moisturizers containing glycerine and emollients can create an environment for improved barrier function which can be further improved by incorporating specific ingredients such as niacinamide.