Miracle-dz/UniFAR-FTUs huggingface dataset:
Cytogenetic abnormalities in PHA‐stimulated lymphocytes from patients with Langerhans cell histiocytosis

The aetiopathogenesis of Langerhans cell histiocytosis (LCH) is still undefined. Constitutional abnormalities in LCH have rarely been reported. One study showed chromosomal instability in lesional cells from three patients. No chromosomal studies are available on peripheral blood lymphocytes. Peripheral blood lymphocytes were analysed for the presence of chromatid and/or chromosomal breaks and structural rearrangements. A fluorescence in situ hybridization (FISH) painting technique was also applied in two cases. Sixteen patients with multisystem (MS, n = 11) or single system (SS, n = 5) LCH were studied, either at the diagnosis (n = 8), during treatment (n = 2) or during follow‐up, when asymptomatic (n = 6). Thirteen patients had chromosomal abnormalities. Eleven patients (69%) had chromatid and chromosomal breaks in 7–45% of cells. Overall, chromosome and chromatid breaks were significantly more frequent in the 11 patients with MS disease than in the five patients with SS disease: the mean percentage of cells showing chromosome and chromatid breaks was 13·4% in MS patients vs. 6·2% in SS patients (P = 0·003). Chromosomal abnormalities may be found in phytohaemagglutinin (PHA)‐stimulated peripheral blood lymphocytes of LCH patients at diagnosis, during the disease course and even during long‐term follow‐up, more frequently in MS disease. Chromosome instability may be considered as either a basic genetic instability or as a landmark of reaction to an environmental agent (viral? ) that, through genome alteration, may play a role in histiocyte proliferation and, in some cases, also in the increased risk of malignancy.
Serum leptin, parathyroid hormone, 1,25-dihydroxyvitamin D, fibroblast growth factor 23, bone alkaline phosphatase, and sclerostin relationships in obesity.

BACKGROUND Obesity is associated with hyperparathyroidism and increased bone mass and turnover, but their pathogeneses are unclear. AIMS Our aim was to determine in obesity interrelationships among serum levels of leptin, the mineral-regulating hormones, bone turnover markers, and sclerostin. METHODS This case-control study was performed in 20 women having bariatric surgery and 20 control women matched for race and age. Anthropometrics and fasting serum biochemistries were measured in controls and in bariatric patients the morning of surgery. RESULTS Body mass index (48.9 vs. 25.4 kg/m(2)), weight (128.6 vs. 71.9 kg), serum leptin (74.6 vs. 25.2 ng/ml), PTH (44.5 vs. 28.8 pg/ml), fibroblast growth factor 23 (FGF23) (42.4 vs. 25.9 pg/ml), and bone alkaline phosphatase (BAP) (25.8 vs. 17.5 U/liter) were higher, but height (162.3 vs. 167.7 cm) and 1,25-dihydroxyvitamin D (1,25D) (39.2 vs. 48.7 pg/ml) were lower in bariatric surgery patients than controls. There was no difference in serum sclerostin, amino-terminal collagen cross-links, 25-hydroxyvitamin D (25D), calcium, phosphate, and creatinine between groups. In the combined sample, leptin was positively related to PTH, FGF23, and BAP but not to 1,25D or sclerostin. Multiple regression analysis demonstrated that PTH was predicted by leptin and Ca (R(2) = 0.39); 1,25D by 25D, FGF23, and phosphate (R(2) = 0.43); FGF23 by leptin and 1,25D (R(2) = 0.27); BAP by leptin, PTH, and Ca (R(2) = 0.39); and sclerostin by leptin and PTH (R(2) = 0.20). CONCLUSIONS Women having bariatric surgery had higher leptin, PTH, FGF23, and BAP and lower 1,25D than controls. Leptin predicted the serum levels of PTH, 1,25D, and FGF23, the mineral-regulating hormones, and BAP, a bone formation marker, in women with body mass index ranging from 13.9-65.8 kg/m(2). The results suggest that leptin has an endocrine or paracrine effect on PTH and FGF23 production and that PTH may be one of the signals in obesity that leads to increased bone mass.
Cohort study of adult patients with haemoglobin SC disease: clinical characteristics and predictors of mortality

Haemoglobin (Hb) SC disease is the second most common subtype of sickle cell disease and is potentially fatal. This study aimed to determine the clinical characteristics, outcome and predictors of mortality in HbSC disease patients, and to compare these findings with patients followed‐up in different centres. Clinical, laboratory and outcome data were collected from a cohort of adult patients with HbSC disease followed between 1991 and 2103. Cox regression multivariate analysis was used to determine predictors of mortality. One hundred and fifty‐five patients were followed‐up over 20 years: 9% died and 70·8% had at least one complication. The most common complications were: painful crises (38·3%), retinopathy (33·8%), cholelithiasis (30·3%), osteonecrosis (24·8%) and sensorineural hearing disorders (9·7%). Frequency of chronic complications was similar in most studies. In multivariate analysis, hearing disorders remained an independent predictor of mortality (Odds Ratio 9·26, 95% confidence interval 1·1–74·8; P = 0·03). It was concluded that patients with HbSC disease receive a late diagnosis and there is remarkable similarity between the studies conducted in different centres around the world. Sensorineural hearing disorders were an independent predictor of mortality, suggesting that it may be useful to implement routine diagnostic screening.
Porotic lesions in immature skeletons from Stara Torina, late medieval Serbia

Porotic lesions of immature skeletons have been attracting scientific attention for more than a century. These changes have been documented worldwide and are considered to be one of the indicators of health and/or nutritional status of past human populations. These lesions have frequently been referred to as a nutritional stress indicator, a manifestation of iron-deficiency anaemia, and a condition caused by chronic infections. In this study, 327 immature skeletons from the medieval graveyard of Stara Torina (Serbia) were examined for macroscopic signs of four types of porotic lesions: cribra orbitalia, femoral cribra, humeral cribra, and porotic hyperostosis. Femoral cribra was observed in 83.25% of femora, humeral cribra in 58.46% of cases, cribra orbitalia in 46.12% of orbits, while porotic hyperostosis was recorded in only 2.94% of skulls. The majority of skeletons affected by cribra presented symmetrical lesions. Association between all types of cribra was recorded in 33.33% of skeletons. Historical data supported the hypothesis that the investigated population was exposed to frequent infections, especially parasitic ones, which led to the development of porotic bone lesions via several mechanisms: parasite-induced blood loss and diarrhoea (both iron and magnesium malabsorption) or anaemia as a hepcidin-mediated body adaptive response to infection. Copyright © 2008 John Wiley & Sons, Ltd.
Chronic inflammatory autoimmune disorders are a risk factor for red blood cell alloimmunization

Fritz, A. , Percy, C. , Jack, A. , Shanmugaratnam, K. , Sobin, L. , Parkin, D.M. & Whelan, S. (eds) (2013) International Classification of Diseases for Oncology, 3rd edn. World Health Organization, Geneva, Switzerland. Gidengil, C.A. , Predmore, Z. , Mattke, S. , van Busum, K. & Kim, B. (2015) Breast implant-associated anaplastic large cell lymphoma: a systematic review. Plastic and Reconstructive Surgery, 135, 713–720. Jewell, M. , Spear, S.L. , Largent, J., Oefelein, M.G. & Adams, Jr, W.P. (2011) Anaplastic large T-cell lymphoma and breast implants: a review of the literature. Plastic and Reconstructive Surgery, 128, 651–661. de Jong, D. , Vasmel, W.L. , de Boer, J.P., Verhave, G. , Barbe, E. , Casparie, M.K. & van Leeuwen, F.E. (2008) Anaplastic large-cell lymphoma in women with breast implants. Journal of the American Medical Association, 300, 2030–2035. Lipworth, L. , Tarone, R. & McLaughlin, J. (2009) Breast implants and lymphoma risk: a review of the epidemiologic evidence through 2008. Plastic and Reconstructive Surgery, 123, 790–793. Spear, S.L. , Largent, J., Kaplowitz, H. , Kaplan, H.M. , Oefelein, M.G. & Beddingfield, F. (2010) Occurrence of anaplastic large cell lymphoma (ALCL) among large multi-center prospective clinical studies of breast implant patients. Plastic and Reconstructive Surgery, 126, 68. Thompson, P.A. & Prince, H.M. (2013) Breast implant-associated anaplastic large cell lymphoma: a systematic review of the literature and mini-meta analysis. Current Hematologic Malignancy Reports, 8, 196–210. United States Food and Drug Administration. Anaplastic large cell lymphoma (ALCL) in women with breast implants: preliminary FDA findings and analyses. 2011. http://www.fda. gov/ MedicalDevices/ProductsandMedicalProcedures/ ImplantsandProsthetics/BreastImplants/ ucm239996.htm Vase, M.O. , Friis, S. , Bautz, A. , Bendix, K. , Sorensen, H.T. & d’Amore, F. (2013) Breast implants and anaplastic large-cell lymphoma: a Danish population-based cohort study. Cancer Epidemiology, Biomarkers & Prevention, 22, 2126–2129. Wang, S.S. , Flowers, C.R. , Kadin, M.E. , Chang, E.T. , Hughes, A.M., Ansell, S.M. , Fedlman, A.L. , Lightfoot, T. , Boffetta, P., Melbye, M. , Lan, Q. , Sampson, J.N. , Morton, L.M. , Zhang, Y. & Weisenburger, D.D. (2014) Medical history, lifestyle, family history, and occupational risk factors for peripheral T-cell lymphomas: the InterLymph Non-Hodgkin Lymphoma Subtypes Project. Journal of the National Cancer Institute Monographs, 2014, 66–75.
Advances in smoking cessation.

Tobacco dependence is a relapsing and addictive chronic disorder and the leading preventable cause of death in the world. Health professionals must diagnose and treat smokers to help them to quit. Smokers who are preparing to quit should receive 2 types of treatments: (1) counseling, aimed at combating their psychologic dependence, and (2) pharmacological therapy to relieve their physical dependence on nicotine. The main objective of this paper is to analyze the advances in smoking cessation treatment. Two components of counseling have proved to be particularly effective in helping smokers to quit: (1) practical counseling (problemsolving/skills training) and (2) social support delivered as a part of treatment. Seven medications have been identified as a first-line pharmacological treatment that should be used by all smokers attempting to quit, except when medically contraindicated or with specific populations for which there is insufficient evidence of effectiveness (ie, pregnant women, smokeless tobacco users, light smokers and adolescents). These medications are as follows: nicotine replacement medications (nicotine gum, nicotine inhaler, nicotine lonzege, nicotine nasal spray and nicotine patch), bupropion and varenicline. Nicotine vaccine represents the most firm therapeutical promise at this moment.
Thyroid function and mortality in older men: a prospective study.

CONTEXT Mild abnormalities of thyroid function have been associated with both beneficial and detrimental effects on mortality. OBJECTIVE Our objective was to determine the association between continuous TSH as well as categories of thyroid function with total and cause-specific mortality in a cohort of older men. DESIGN, SETTING, AND PARTICIPANTS Data were analyzed from the Osteoporotic Fractures in Men (MrOS) study, a cohort of community-dwelling U.S. men aged 65 yr and older. A total of 1587 participants randomly selected for thyroid function testing were included in this analysis. TSH and free T4 were measured at baseline, and four categories of thyroid function were defined. (subclinical hyperthyroid; euthyroid; subclinical hypothyroid TSH<10 mIU/liter; and subclinical hypothyroid, TSH≥10 mIU/liter.) MAIN OUTCOME MEASURE Total mortality, cardiovascular (CV) and cancer deaths were confirmed by review of death certificates. RESULTS There were 432 deaths over a mean follow-up of 8.3 yr. In fully adjusted models, there was no association between baseline TSH and any death [relative hazard (RH)=1.01 per mIU/liter, 95% confidence interval (CI)=0.95-1.06], CV death (RH=1.05 per mIU/liter, 95% CI 0.96-1.15), or cancer death (RH=0.96 per mIU/liter, 95% CI=0.85-1.07). There was also no statistically significant association between thyroid function category and total or cause-specific mortality, but few men (n=8) had subclinical hypothyroidism with TSH levels of 10 mIU/liter or higher. CONCLUSIONS A single measurement of thyroid function did not predict total or cause-specific mortality in this cohort. These data support neither a beneficial nor a detrimental effect of subclinical thyroid dysfunction in older men. SUMMARY Subclinical thyroid dysfunction is not associated with an increased risk of all-cause or CV mortality in older men.
Long-Term Reliability of the Timed Up-and-Go Test among Community-Dwelling Elders

The purpose of this study was to describe the long-term reliability of the Timed Up and Go (TUG) test among community dwelling elders (mean age = 75 years). Sixteen women and 4 men were tested 3 times (baseline, 6 weeks, and 12 weeks) at a community senior center. The reliability across the 3 tests was good (intraclass correlation coefficient = .80). The TUG times decreased significantly (p=.02) over the first (mean = 10.1 sec), second (mean = 9.1 sec), and third (mean = 8.9 sec) tests, but between test comparisons (Bonferroni adjusted t-tests) demonstrated no significant differences between any pair of tests. The technical error of measurement was 3.2 sec between the first and second tests and 4.0 sec between the first and third tests; but it was only 0.1 sec between the second and third tests. Bland-Altman plots showed the following 95 percent limits of agreement: test 1 and test 2 (2.9 to 4.9 sec), test 1 and test 3 (3.1 to 5.7 sec), test 2 and test 3 (3.4 to 3.9 sec). The results of this study corroborate those of previous studies supporting the reliability of the TUG test among cognitively intact individuals. The results, however, suggest that considerable differences may exist between tests conducted over a period of weeks. Consequently, differences of several seconds may be necessary to conclude that a real change in performance has occurred. This is particularly true between a first and second test.
The presence of genomic imbalances is associated with poor outcome in patients with burkitt lymphoma treated with dose‐intensive chemotherapy including rituximab

The introduction of Rituximab has improved the outcome and survival rates of Burkitt lymphoma (BL). However, early relapse and refractoriness are current limitations of BL treatment and new biological factors affecting the outcome of these patients have not been explored. This study aimed to identify the presence of genomic changes that could predict the response to new therapies in BL. Forty adolescent and adult BL patients treated with the Dose‐Intensive Chemotherapy Including Rituximab (Burkimab) protocol (Spanish Programme for the Study and Treatment of Haematological Malignancies; PETHEMA) were analysed using array‐based comparative genomic hybridization (CGH). In addition, the presence of TP53, TCF3 (E2A), ID3 and GNA13 mutations was assessed by next‐generation sequencing (NGS). Ninety‐seven per cent of the patients harboured genomic imbalances. Losses on 11q, 13q, 15q or 17p were associated with a poor response to Burkimab therapy (P = 0·038), shorter progression‐free survival (PFS; P = 0·007) and overall survival (OS; P = 0·009). The integrative analysis of array‐CGH and NGS showed that 26·3% (5/19) and 36·8% (7/19) of patients carried alterations in the TP53 and TCF3 genes, respectively. TP53 alterations were associated with shorter PFS (P = 0·011) while TCF3 alterations were associated with shorter OS (P = 0·032). Genetic studies could be used for risk stratification of BL patients treated with the Burkimab protocol.
Identification of novel biomarkers in chronic immune thrombocytopenia (ITP) by microarray‐based serum protein profiling

The pathological mechanisms underlying the development of immune thrombocytopenia (ITP) are unclear and its diagnosis remains a process of exclusion. Currently, there are no known specific biomarkers for ITP to support differential diagnosis and treatment decisions. Profiling of serum proteins may be valuable for identifying such biomarkers. Sera from 46 patients with primary chronic ITP and 34 healthy blood donors were analysed using a microarray of 755 antibodies. We identified 161 differentially expressed proteins. In addition to oncoproteins and tumour‐suppressor proteins, including apoptosis regulator BCL2, breast cancer type 1 susceptibility protein (BRCA1), Fanconi anaemia complementation group C (FANCC) and vascular endothelial growth factor A (VEGFA), we detected six anti‐nuclear autoantibodies in a subset of ITP patients: anti‐PCNA, anti‐SmD, anti‐Ro/SSA60, anti‐Ro/SSA52, anti‐La/SSB and anti‐RNPC antibodies. This finding may provide a rational explanation for the association of ITP with malignancies and other autoimmune diseases. While RUNX1mRNA expression in the peripheral blood mononuclear cells (PBMC) of patients was significantly downregulated, an accumulation of RUNX1 protein was observed in the platelets of ITP patients. This may indicate dysregulation of RUNX1 expression in PBMC and megakaryocytes and may lead to an imbalanced immune response and impaired thrombopoiesis. In conclusion, we provide novel insights into the pathogenic mechanisms of ITP that warrant further exploration.
Thyroid dysfunction and fibrin network structure: a mechanism for increased thrombotic risk in hyperthyroid individuals.

CONTEXT Hyperthyroidism is associated with increased thrombosis risk, and fibrin clot structure determines susceptibility to vascular thrombotic events. OBJECTIVE Our objective was to investigate clot formation and lysis in hyperthyroidism using observational and interventional studies. DESIGN Ex vivo fibrin clot structure/fibrinolysis and plasma levels of thrombotic/inflammatory markers were investigated in hyperthyroid individuals (n = 24) and matched controls (n = 19), using turbidimetric assays, ELISA, and confocal and electron microscopy. The effects of normalizing thyroid function were analyzed (n = 19) and the role of short-term exogenous hyperthyroidism in healthy volunteers studied (n = 16). RESULTS Hyperthyroid subjects displayed higher clot maximum absorbance compared with controls (0.41 ± 0.03 and 0.27 ± 0.01 arbitrary units, respectively; P < 0.01), and longer clot lysis time (518 ± 23 and 461 ± 18 sec, respectively; P < 0.05), which correlated with free T(4) levels. Plasma levels of fibrinogen and plasminogen activator inhibitor-1 were significantly higher in patients compared with controls. Normalizing thyroid function in 19 subjects was associated with lower maximum absorbance and shorter lysis time, accompanied by reduction in fibrinogen, plasminogen activator inhibitor-1, and D-dimer levels. Complement C3, but not C-reactive protein, levels were higher in hyperthyroid subjects compared with controls (0.92 ± 0.05 and 0.64 ± 0.03 g/liter, respectively; P < 0.01), correlated with clot structure parameters, and decreased after intervention. Confocal and electron microscopy confirmed more compact clots and impaired fibrinolysis during hyperthyroidism. Exogenous hyperthyroidism in healthy volunteers had no effect on any of the clot structure parameters. CONCLUSIONS Endogenous hyperthyroidism is associated with more compact clots and resistance to fibrinolysis ex vivo, related to the degree of hyperthyroidism and C3 plasma levels, and these changes are modulated by achieving euthyroidism. Altered clot structure/lysis may be one mechanism for increased thrombotic risk in hyperthyroidism.
The Economic Impact of S-100B as a Pre-Head CT Screening Test on Emergency Department Management of Adult Patients with Mild Traumatic Brain Injury

Abstract Recent research suggests that serum S-100B may serve as a good pre–head computed tomography (CT) screening test because of its high sensitivity for abnormal head CT scans. The potential economic impact of using S-100B in the emergency department setting for management of adult patients with isolated mild traumatic brain injury (mTBI) has not been evaluated despite its clinical implementation in Europe. Using evidence from the literature, we constructed a decision tree to compare the average cost per patient of using S-100B as a pre–head CT screening test to the current practice of ordering CT scans based on patients' presenting symptoms without the aid of S-100B. When compared to scanning 45–77% of isolated mTBI patients based upon their presenting symptoms, using S-100B as a pre-head CT screen does not lower hospital costs ($281 versus $160), primarily due to its low specificity for abnormal head CT scans. Sensitivity analyses showed, however, that S-100B becomes cost-lowering when the proportio.
Efficiency of dental health care in Federation of Bosnia and Herzegovina

Introduction: Despite the great improvements in the oral health status of the population across the world, oral diseases remains a major public health issue connected with a lost of numerous school days for childrenand absenteeism from work in adults. This effect is particularly evident in low and middle income countries as Bosnia and Herzegovina. This retrospective study presents the effi ciency of dental health carein Federation of Bosnia and Herzegovina measured by number of visits and performed dental treatments during the time period of six years, from 2005-2011.Methods: Data were collected by evaluation of the results obtained by forms which are mandatory to be completed by dentists.Results: The number of graduated dentists from 2007 to 2011 decreased from 108 in 2007 to 68 in 2011. In the same time, number of dentists employed in public sector slightly increased from 529 in 2005 to587 in 2011. Number of extracted permanent teeth decreased from the 412 extracted permanent teeth per dentist in 2005 to 364 in 2011. Small number of fi lled primary teeth comparing to large number ofextracted primary teeth showed negligence in their treatment.Conclusion: Having in mind that improving oral health in developing countries is a very challenging objective we can conclude that dental health care system in Federation of Bosnia and Herzegovina need to bereform in order to improve oral health in general, particularly in children population.
Mutations affecting both the rearranged and the unrearranged PML alleles in refractory acute promyelocytic leukaemia

Acute promyelocytic leukaemia (APL) is characterized by the PML/RARA fusion transcript. PML and RARA mutations have been shown to directly respond to arsenic trioxide (ATO) and all‐trans retinoic (ATRA). We analysed the prevalence of PML mutations in 32 patients with de novo or therapy‐related APL (t‐APL; n = 5), treated with ATO. We identified one ATO‐resistant t‐APL patient, who presented a PML A216T mutation in both the rearranged and unrearranged PML alleles, and two mutations in the rearranged RARA gene. In this patient, subclones with different PML and RARA mutations acquired clonal dominance during the disease course, probably leading to treatment resistance.