Miracle-dz/UniFAR-FTUs huggingface dataset:
Long‐term ursodeoxycholic acid delays histological progression in primary biliary cirrhosis

Primary biliary cirrhosis (PBC) is a progressive cholestatic liver disease frequently leading to development of cirrhosis and its complications. Ursodeoxycholic acid (UDCA) is a beneficial medical therapy for patients with PBC. Improvement in some histological features, but not in histological stage, has been reported after 2 years of UDCA therapy. Thus, longer follow‐up may be necessary to determine whether UDCA has a favorable effect on histological stage of disease and progression to cirrhosis. Our aim was to determine the long‐term effects of UDCA therapy on histological stage and progression to cirrhosis in patients with PBC. Sixteen unselected patients with noncirrhotic PBC who had been on long‐term UDCA therapy (13‐15 mg/kg/d) for 6.6 ± 0.4 years (range, 5‐9 years) were identified and their histological finding during treatment compared with that of 51 noncirrhotic patients with PBC who had received ineffective therapy (d‐penicillamine [DPCA] or placebo) for 5.6 ± 0.07 years (range, 5‐8 years). Histological stage was determined using the Ludwig classification. The rate of progression to cirrhosis (stage 4) was significantly less in the UDCA group than in the control group (13% vs. 49%P= .009). Although the overall rate of progression of histological stage was less in the UDCA group than in the control group (50% vs. 71%), this difference was not significant (P= .1). A marked improvement in liver biochemistries and Mayo risk score was noted in all patients during UDCA therapy; however, this improvement was not significantly different between patients who progressed and those who did not. In conclusion, long‐term UDCA therapy appeared to delay the development of cirrhosis in PBC.
An enhanced CRF-based system for disease name entity recognition and normalization on BioCreative V DNER Task

Disease plays a central role in many areas of biomedical research and healthcare. However, the rapid growth of disease and treatment research creates barriers to the knowledge aggregation of PubMed database. Thus, a framework of disease mention recognition and normalization has become increasingly important for biomedical text mining. In this work, we utilize conditional random fields (CRFs) to develop a recognition system and optimize the results by customizing several post-processing steps, such as abbreviation resolution and consistency improvement. At the DNER subtask of BioCreative V CDR task, the system performance of disease normalization is 0.8646 of F-measure, especially a high precision (0.8963) on the normalization task.
Cloning of the gene encoding Streptococcin A-FF22, a novel lantibiotic produced by Streptococcus pyogenes, and determination of its nucleotide sequence

Streptococcin A-FF22 (SA-FF22) is a lantibiotic produced by Streptococcus pyogenes FF22. The nucleotide sequence of the SA-FF22 structural gene (scnA) was determined and shown to encode a 51-amino-acid prepeptide. The proteolytic processing site of the SA-FF22 prepeptide differs from that which characterizes other type A lantibiotics.
Determinants of fertility in developing countries.

The contribution of agricultural modernization to changes in fertility in developing countries was examined. A model for the determinants of both fertility and infant mortality--hypothesized to be positively related--was specified and applied to cross-sectional data for 75 developing countries for the year 1971. The infant mortality rate, productivity per unit of labor and land, and density of population for agricultural land were highly correlated with the crude birth rate. The only other exogenous variables highly correlated with each other were productivity per unit of labor and infant mortality, and productivity per unit of land and population density for agricultural areas. The coefficient of population density of agricultural areas suggested a negative impact of density on fertility. The infant mortality rate, productivity per unit of land and labor, and density of population of agricultural areas explained 85% of the intercountry variation in fertility. The infant mortality rate, productivity of land, and productivity of labor were of descending order of importance in determining the crude birth rates in the countries analyzed. 68% of the intercountry variation in infant mortality was explained by fertility, adult literacy, per capita energy consumption, gini-coefficient of income distribution, population per hospital bed, and protein supply. Adult literacy, crude birth rates, population per hospital bed, per capita energy consumption, per capita protein supply, and gini-coefficient of income distribution were of descending order of importance in determining infant mortality rates. All of the variables that affected infant mortality directly affected fertility indirectly; conversely, all the variables that affected fertility directly affected infant mortality indirectly. Overall, these results confirm that agricultural modernization does exert an effect on fertility. The task in developing countries is to break the vicious cycle of infant mortality and fertility. This can be achieved both through family planning programs and the diffusion of health programs to lower infant mortality.
Retinoic acid blocks adipogenesis by inhibiting C/EBPbeta-mediated transcription

Adipocyte differentiation is thought to involve sequential induction of the transcription factors C/EBPbeta, peroxisome proliferator-activated receptor gamma (PPARgamma), and C/EBPalpha. C/EBPalpha expression is both necessary and sufficient for adipocyte differentiation. Here we report that ectopic expression of either C/EBPalpha or C/EBPbeta induces PPARgamma expression and adipogenesis and that retinoic acid (RA) completely inhibits adipogenesis by either form of C/EBP. In studies of normal preadipocytes, RA does not prevent C/EBPbeta induction but blocks induction of PPARgamma, C/EBPalpha, and adipogenesis. In transient transfection studies, liganded RA receptor (RAR) specifically blocks transcriptional activation by either C/EBPalpha or C/EBPbeta. These results strongly suggest that C/EBPalpha substitutes for C/EBPbeta to induce adipocyte differentiation and that liganded RAR inhibits adipogenesis by blocking C/EBPbeta-mediated induction of downstream genes.
Firm Leverage, Consumer Demand, and Employment Losses during the Great Recession

We argue that firms’ balance sheets were instrumental in the propagation of shocks during the Great Recession. Using establishment-level data, we show that firms that tightened their debt capacity in the run-up to the Great Recession (“highleverage firms”) exhibit a significantly larger decline in employment in response to household demand shocks than firms that freed up debt capacity (“low-leverage firms”). In fact, all of the job losses associated with falling house prices during the Great Recession are concentrated among establishments of high-leverage firms. At the county level, we show that counties with a larger fraction of establishments belonging to high-leverage firms exhibit a significantly larger decline in employment in response to household demand shocks. Thus, firms’ balance sheets also matter for aggregate employment.
CELL MEMBRANE DNA: A NEW TARGET FOR PSORALEN PHOTOADDUCT FORMATION

The effects of 8‐methoxypsoralen plus long wavelength ultraviolet radiation on cell membrane DNA were examined. Treatment of human lymphocytes with 100 ng/ml 8‐methoxypsoralen and 5 J/cm2 UVA led to the formation of 7.1 ±3.8 photoadducts per million bases. A monoclonal antibody, specific for 8‐methoxypsoralen 4′,5′4nonoadducts, was used to detect photoadducts in the cell membrane DNA of human lymphocytes and three lymphoblastoid cell lines. Treatment of lymphocytes with 8‐MOP and UVA reduced the lymphocyte DNA binding capacity by 56%. Cell membranes of normal lymphocytes were shown to contain three high affinity DNA binding proteins of 28, 59, and 79 kDa, respectively.
Poor predictive value of cytomegalovirus (CMV)-specific T cell assays for the development of CMV retinitis in patients with AIDS.

BACKGROUND We examined the potential clinical utility of using a cytomegalovirus (CMV)-specific T cell immunoassay to determine the risk of developing new-onset CMV retinitis (CMVR) in patients with acquired immunodeficiency syndrome (AIDS). METHODS CMV-specific T cell assays were performed by multiparameter flow cytometry using stored peripheral blood mononuclear cells that had been obtained in an observational study 2-6 months before new-onset CMVR was diagnosed in case patients (at a study visit during which a dilated ophthalmologic examination revealed no evidence of CMVR) and at the same study visit in control subjects (matched by absolute CD4(+) T cell count at entry) who did not subsequently develop retinitis during 1-6 years of study follow-up. RESULTS There were no significant differences in CMV-specific CD4(+) or CD8(+) T cell interferon-gamma or interleukin-2 expression in peripheral blood mononuclear cells from case patients and control subjects. Although there were trends toward lower percentages and absolute numbers of CMV-specific, cytokine-expressing CD8(+) T cells with a "late memory" phenotype (CD27(-)CD28(-)) as well as with an "early memory" phenotype (CD27(+)CD28(+)CD45RA(+)) in case patients than in control subjects, these differences were not statistically significant. CONCLUSIONS Many studies have reported that CMV-specific CD4(+) and CD8(+) T cell responses distinguish patients with active CMVR (i.e., who lack CMV-protective immunity) from those with inactive CMVR after immune restoration by antiretroviral treatment (i.e., who have CMV-protective immunity). However, the multiple CMV-specific immune responses we measured do not appear to have clinical utility for predicting the risk for patients with AIDS of developing new-onset CMVR with sufficient accuracy to be used in guiding therapeutic management.
Low birth weight is not associated with clinically overt thyroid disease: a population based twin case‐control study

In recent years low birth weight has been proposed as a risk factor for the development of several chronic diseases in adult life, including diabetes and subclinical autoimmune thyroid disease. The association could, however, also be due to genetic or environmental factors affecting both birth weight and adverse health outcomes in adult life. Moreover, it is at present unknown whether or not low birth weight is associated with an increased risk of developing clinically overt thyroid disease. The aim of the present study was to investigate the impact of birth weight and several other birth characteristics on the development of clinically overt thyroid disease.
Factors that Influence Financial Leverage of Small Business Firms in India

The purpose of this study is to examine the factors that influence financial leverage of small business firms in India. This study also seeks to extend the findings of Michaelas et al. (1999). Small business owners from Punjab area of India were surveyed in order to gather information. Subjects were asked about their perceptions, beliefs, and feelings regarding the factors that influence financial leverage of their firms. This study utilized survey research (a non-experimental field study design). The findings of this paper show that small business growth, small business performance, total assets, sales, tax, and family have positive influence on the financial leverage of small business firms in India. This study contributes to the literature on the factors that influence financial leverage of small business firms. The findings may be useful for the financial managers, investors, and financial management consultants.
Flagellar Glycosylation in Burkholderia pseudomallei and Burkholderia thailandensis

ABSTRACT Glycosylation of proteins is known to impart novel physical properties and biological roles to proteins from both eukaryotes and prokaryotes. In this study, gel-based glycoproteomics were used to identify glycoproteins of the potential biothreat agent Burkholderia pseudomallei and the closely related but nonpathogenic B. thailandensis. Top-down and bottom-up mass spectrometry (MS) analyses identified that the flagellin proteins of both species were posttranslationally modified by novel glycans. Analysis of proteins from two strains of each species demonstrated that B. pseudomallei flagellin proteins were modified with a glycan with a mass of 291 Da, while B. thailandensis flagellin protein was modified with related glycans with a mass of 300 or 342 Da. Structural characterization of the B. thailandensis carbohydrate moiety suggests that it is an acetylated hexuronic acid. In addition, we have identified through mutagenesis a gene from the lipopolysaccharide (LPS) O-antigen biosynthetic cluster which is involved in flagellar glycosylation, and inactivation of this gene eliminates flagellar glycosylation and motility in B. pseudomallei. This is the first report to conclusively demonstrate the presence of a carbohydrate covalently linked to a protein in B. pseudomallei and B. thailandensis, and it suggests new avenues to explore in order to examine the marked differences in virulence between these two species.
Milk intake and bone mineral acquisition in adolescent girls: randomised, controlled intervention trial

Abstract Objectives: To investigate the effect of milk supplementation on total body bone mineral acquisition in adolescent girls. Design: 18 month, open randomised intervention trial. Subjects: 82 white girls aged 12.2 (SD 0.3) years, recruited from four secondary schools in Sheffield. Intervention: 568 ml (one pint) of whole or reduced fat milk per day for 18 months. Main outcome measures: Total body bone mineral content and bone mineral density measured by dual energy x ray absorptiometry. Outcome measures to evaluate mechanism included biochemical markers of bone turnover (osteocalcin, bone alkaline phosphatase, deoxypyridinoline, N-telopeptide of type I collagen), and hormones important to skeletal growth (parathyroid hormone, oestradiol, insulin-like growth factor I). Results: 80 subjects completed the trial. Daily milk intake at baseline averaged 150 ml in both groups. The intervention group consumed, on average, an additional 300 ml a day throughout the trial. Compared with the control group, the intervention group had greater increases of bone mineral density (9.6% v 8.5 %, P=0.017; repeated measures analysis of variance) and bone mineral content (27.0% v 24.1 %, P=0.009). No significant differences in increments in height, weight, lean body mass, and fat mass were observed between the groups. Bone turnover was not affected by milk supplementation. Serum concentrations of insulin-like growth factor I increased in the milk group compared with the control group (35% v 25 %, P=0.02). Conclusion: Increased milk consumption significantly enhances bone mineral acquisition in adolescent girls and could favourably modify attainment of peak bone mass. Key messages Osteoporosis is a major public health problem; 40% of women will sustain an osteoporotic fracture Maximising peak bone mass at skeletal maturity may be one of the most important protective measures against fracture in later life Adolescence is a critical time for bone mineral acquisition An increase in milk consumption among adolescent girls resulted in significant gains in bone mineral over an 18 month period This simple intervention indicates that increased milk consumption may be associated with higher peak bone mass
The patient knows best: significant change in the physical component of the Multiple Sclerosis Impact Scale (MSIS-29 physical)

Aim: The aims of this study were to determine the reliability, responsiveness and minimally important change score of the Multiple Sclerosis Impact Scale (MSIS)-29 physical using the Expanded Disability Status Scale (EDSS) as an anchor measure. Methods: 214 patients with multiple sclerosis (MS) (EDSS 0–8.5) had concurrent MSIS-29 and EDSS assessments at baseline and at up to 4 years of follow-up. Results: 116 patients had unchanged EDSS scores. Stability of the MSIS-29 physical (mean change 0.1 points) was better in the 85 patients with EDSS 0–5.0 than in the 31 patients with EDSS 5.5–8.5 in whom the MSIS-29 physical score fell by 8 points, a response shift phenomenon. A floor effect for the MSIS-29 was observed in 5% of stable patients at both time points. 98 patients experienced EDSS change with moderately strong statistically significant correlations between change scores in the EDSS and the MSIS-29 physical (r = 0.523, p<0.0001). Effect sizes for MSIS-29 physical change were moderate to large. Using receiver operating characteristic curves, the MSIS-29 change score which produced a combination of optimal sensitivity and specificity was chosen for both EDSS ranges. For EDSS range 5.5–8, a change score of 8 had a sensitivity of 87% and specificity of 67%. For EDSS 0–5.0, a change score of 7 had a sensitivity of 78% and a specificity of 51%. Conclusions: The MSIS-29 physical performs well over time, and is suitable for use in trials; a minimal change score of 8 points in the MSIS-29 is clinically significant.
C5b-9 does not mediate chronic tubulointerstitial disease in the absence of proteinuria.

BACKGROUND In nephrotic glomerular diseases, the intratubular assembly of the membrane attack complex (C5b-9) is one of the principal mediators of chronic tubulointerstitial damage. Here, we examined whether C5b-9 has a pathogenic role in tubulointerstitial disease in the absence of proteinuria. METHODS Three pathophysiologically distinct models of nonproteinuric chronic tubulointerstitial disease were induced in Piebald-Viral-Glaxo (PVG) rats, with or without C6 deficiency (C6+ and C6): (1) unilateral ureteric obstruction (UUO, days 1, 3, 6, 14, and 21; N= 5-6/group); (2) cyclosporine (CsA) nephropathy (15 mg/kg SC daily with 0.05% sodium diet; day 14, 35 N= 9/group); and (3) streptozotocin (STZ)-induced diabetes (day 90, N= 8/group). RESULTS The peritubular deposition of C5b-9 increased in all three models. In UUO, the number of vimentin-positive tubules, interstitial volume expansion, and monocyte accumulation were similar in both the C6+ and C6- groups at all time points. There was a trend toward an earlier peak in myofibroblast accumulation in C6- rats with UUO (d3 vs. d6; P= 0.05), but this did not prevent fibrosis at later time points. In CsA nephropathy, cortical tubulointerstitial damage was also similar in both C6+ and C6- groups on day 14, despite equivalent CsA trough levels. Finally, in STZ-induced diabetes, rats did not develop proteinuria, and tubulointerstitial disease (distal tubule glycogen nephrosis, interstitial volume expansion, and tubular dilatation) was not altered by C6 deficiency. CONCLUSION These data suggest that, in contrast to proteinuric states, C5b-9 does not have a significant impact on the progression of tubulointerstitial damage in nonproteinuric chronic renal disease.
Histamine enhances granulocyte‐macrophage colony‐stimulating factor and interleukin‐6 production by human peripheral blood mononuclear cells

The effect of histamine on the production of cytokines by subpopulations of mononuclear cells was studied. A 3.5‐fold increase in the number of myeloid colony‐forming units (CFU‐C) was observed when bone marrow cells were cultured in the presence of conditioned medium prepared from nonadherent mononuclear cells cultured with 10−4 M histamine (CM‐histamine) compared with phosphate‐buffered saline (CM‐PBS). Using ELISA and radioimmunoassay kits, histamine was found to enhance the production of GM‐CSF (9.6‐fold) and IL‐6 (8.2‐fold) by mononuclear cells but not by nonadherent cells or large granular lymphocytes. Anti‐GM‐CSF and anti‐IL‐6 antibodies markedly blocked cytokine activity in CM‐PBS, whereas the blocking effect in CM‐histamine was moderate, indicating enhanced GM‐CSF and IL‐6 activity in CM‐histamine. No GM‐CSF or IL‐6 levels could be detected in CM‐histamine or CM‐PBS prepared from CD3+, CD4+, or CD8+ lymphocytes. Preincubation of CM‐histamine with H1 and H2 receptor antagonists resulted in complete blocking of the histamine‐enhanced colony‐stimulating activity. We conclude that histamine is able to activate human mononuclear cells to generate cytokines such as GM‐CSF and IL‐6 via H1 and H2 receptors.
Environment shapes invertebrate assemblage structure differences between volcanic spring-fed and runoff rivers in northern California

Flow variability plays an important role in structuring lotic communities, yet comparatively little is known about processes governing assemblage dynamics in stream ecosystems with stable environmental conditions, such as spring-fed rivers. Volcanic spring-fed rivers (hereafter spring-fed rivers) occur in geologically active landscapes of the western USA and around the globe. We sampled invertebrate assemblages and quantified primary productivity and habitat characteristics of spring-fed and runoff rivers in northern California over 4 seasons. We predicted that abiotic factors would be more stable and nutrient availability greater and that invertebrate density would be greater and diversity lower in spring-fed than in runoff rivers. Runoff rivers exhibited high variability in discharge and temperature, whereas spring-fed rivers were relatively stable with high naturally occurring nutrient levels. On average, NO3− and PO43− concentrations were 40× greater in spring-fed than in runoff rivers. Spring-fed rivers supported nearly 7 to 16× greater densities of invertebrates than runoff systems, depending on season. However, invertebrate species richness was greater in runoff rivers in all seasons. Spring-fed river invertebrate assemblages were strongly correlated with elevated nutrient concentrations and basal C sources, whereas runoff assemblages were associated with discharge variability and median substrate size. We suggest that strong differences in abiotic variability between spring-fed and runoff rivers play an important role in determining invertebrate assemblage structure. Because spring-fed rivers exhibit more stable temperatures throughout the year and lower temperatures during the summer than runoff rivers, they may provide essential refugia for coldwater taxa in a warming climate.
Mini review: Multifaceted role played by cyclin D1 in tumor behavior

The objective of this paper is to discuss and put forward the various diversified roles of cyclin D1 in cancer. Neoplasia is defined by abnormal regulation of the cell cycle. Cyclin D1 could be a protein derived from the PRAD1, CCND1, or bcl-1 sequence on body 11q13 that is concerned in each traditional regulation of the cell cycle and pathologic process. Within the G1 (resting) part of the cell cycle, cyclin D1 in conjunction with its cyclin-dependent enzyme (cyclin-dependent kinase) partner is accountable for transition to the S (DNA synthesis) part by phosphorylating the merchandise of the metastatic tumor sequence (protein retinoblastoma) that then releases transcription factors vital within the initiation of DNA replication. Amplification of the sequence or overexpression of the cyclin D1 releases a cell from its traditional controls and causes transformation to a malignant composition. Analysis of those changes provides vital diagnostic information in oral carcinogenesis and is of prognostic value in several cancers. Data of cyclin D1's role in malignancy at the assorted sites provide a basis on which future treatment directed against this molecule will proceed.