Miracle-dz/UniFAR-FTUs huggingface dataset:
Perturbed MafB/GATA1 axis after burn trauma bares the potential mechanism for immune suppression and anemia of critical illness

Patients who survive initial burn injury are susceptible to nosocomial infections. Anemia of critical illness is a compounding factor in burn patients that necessitates repeated transfusions, which further increase their susceptibility to infections and sepsis. Robust host response is dependent on an adequate number and function of monocytes/macrophages and dendritic cells. In addition to impaired RBC production, burn patients are prone to depletion of dendritic cells and an increase in deactivated monocytes. In steady‐state hematopoiesis, RBCs, macrophages, and dendritic cells are all generated from a common myeloid progenitor within the bone marrow. We hypothesized in a mouse model of burn injury that an increase in myeloid‐specific transcription factor V‐maf musculoaponeurotic fibrosarcoma oncogene homolog B at the common myeloid progenitor stage steers their lineage potential away from the megakaryocyte erythrocyte progenitor production and drives the terminal fate of common myeloid progenitors to form macrophages vs. dendritic cells, with the consequences being anemia, monocytosis, and dendritic cell deficits. Results indicate that, even though burn injury stimulated bone marrow hematopoiesis by increasing multipotential stem cell production (LinnegSca1poscKitpos), the bone marrow commitment is shifted away from the megakaryocyte erythrocyte progenitor and toward granulocyte monocyte progenitors with corresponding alterations in peripheral blood components, such as hemoglobin, hematocrit, RBCs, monocytes, and granulocytes. Furthermore, burn‐induced V‐maf musculoaponeurotic fibrosarcoma oncogene homolog B in common myeloid progenitors acts as a transcriptional activator of M‐CSFR and a repressor of transferrin receptors, promoting macrophages and inhibiting erythroid differentiations while dictating a plasmacytoid dendritic cell phenotype. Results from small interfering RNA and gain‐of‐function (gfp‐globin transcription factor 1 retrovirus) studies indicate that targeted interventions to restore V‐maf musculoaponeurotic fibrosarcoma oncogene homolog B/globin transcription factor 1 balance can mitigate both immune imbalance and anemia of critical illness.
Public debt growth, great recession and fiscal consolidation-the Serbian episode

This paper analyses the dynamics of public debt growth in Serbia between the fourth quarter of 2004 (2004Q4) and the same quarter of 2017 (2017Q4). The empirical estimates capture the upward shift in public debt growth from the onset of the Great Recession. The results also show how policy makers have managed to curb the growth of public indebtedness in Serbia between 2014Q4-2017Q4. The government should, however, put greater fiscal efforts to reduce the overall share of public debt in gross domestic product in accordance with the fiscal rules of the Republic of Serbia and the Maastricht convergence criteria.
Agriculture and farming related activities: their actors and position in the LEADER approac

The paper aims to fill in the gap existing in the Czech Republic as for the research about the nature and impacts of the LEADER approach. The focus of the paper is to show how farming and agriculture related activities are addressed under the LEADER scheme in the European context and how does the LEADER influence the position of farming and related industries in rural development. Such outline is considered as the starting point for in-depth research in the LEADER in Czechia. To achieve such goal, the paper analyses the reports about the corresponding projects published in the Leader+ Magazine (edited by Leader+ Observatory). The analysis documents that LEADER supports collaborative actions. It is obvious that the farmers mostly participate in projects aiming at adding value to local product but they are not too active in improvement of the quality of life in rural areas. It opens the room for non-farming actors for their higher participation in rural development and thus it supports the reformulation of Common Agricultural Policy.
Genetic Background of Celiac Disease and Its Clinical Implications

Celiac disease (CD) is a complex genetic disorder with multiple contributing genes. Linkage studies have identified several genomic regions that probably contain CD susceptibility genes. The most important genetic factors identified are HLA-DQ2 and HLA-DQ8, which are necessary but not sufficient to predispose to CD. The associations found in non-HLA genomewide linkage and association studies are much weaker. This might be because a large number of non-HLA genes contributes to the pathogenesis of CD. Hence, the contribution of a single predisposing non-HLA gene might be quite modest. Practically all CD patients carry HLA-DQ2 or HLA-DQ8, while the absence of these molecules has a negative predictive value for CD close to 100%. Genetic risk profiles for CD would be helpful in clinical practice for predicting disease susceptibility and progression.
Competitive Interactions in Mixed-Species Biofilms Containing the Marine Bacterium Pseudoalteromonas tunicata

ABSTRACT Pseudoalteromonas tunicata is a biofilm-forming marine bacterium that is often found in association with the surface of eukaryotic organisms. It produces a range of extracellular inhibitory compounds, including an antibacterial protein (AlpP) thought to be beneficial for P. tunicata during competition for space and nutrients on surfaces. As part of our studies on the interactions between P. tunicata and the epiphytic bacterial community on the marine plant Ulva lactuca, we investigated the hypothesis that P. tunicata is a superior competitor compared with other bacteria isolated from the plant. A number of U. lactuca bacterial isolates were (i) identified by 16S rRNA gene sequencing, (ii) characterized for the production of or sensitivity to extracellular antibacterial proteins, and (iii) labeled with a fluorescent color tag (either the red fluorescent protein DsRed or green fluorescent protein). We then grew single- and mixed-species bacterial biofilms containing P. tunicata in glass flow cell reactors. In pure culture, all the marine isolates formed biofilms containing microcolony structures within 72 h. However, in mixed-species biofilms, P. tunicata removed the competing strain unless its competitor was relatively insensitive to AlpP (Pseudoalteromonas gracilis) or produced strong inhibitory activity against P. tunicata (Roseobacter gallaeciensis). Moreover, biofilm studies conducted with an AlpP− mutant of P. tunicata indicated that the mutant was less competitive when it was introduced into preestablished biofilms, suggesting that AlpP has a role during competitive biofilm formation. When single-species biofilms were allowed to form microcolonies before the introduction of a competitor, these microcolonies coexisted with P. tunicata for extended periods of time before they were removed. Two marine bacteria (R. gallaeciensis and P. tunicata) were superior competitors in this study. Our data suggest that this dominance can be attributed to the ability of these organisms to rapidly form microcolonies and their ability to produce extracellular antibacterial compounds.
Early metabolic abnormalities in adolescent girls with polycystic ovarian syndrome.

OBJECTIVE To investigate insulin sensitivity and secretion in young adolescent girls with childhood onset polycystic ovarian syndrome (PCOS) and to identify the early metabolic derangement(s). STUDY DESIGN Twelve obese girls with PCOS (age 12.0+/-0.7 years) were compared with 10 obese nonhyperandrogenic girls (control group). The groups were matched for age, percent body fat, and abdominal fat. All subjects underwent a 3-hour hyperinsulinemic (80 mu/m(2)/min)-euglycemic clamp to determine in vivo insulin sensitivity and a 2-hour hyperglycemic clamp (225 mg/dL) to determine insulin secretion. Fasting hepatic glucose production was determined with the use of [6,6-(2)H(2)]glucose. RESULTS Fasting glucose and hepatic glucose production were comparable between the 2 groups, but fasting insulin was 2-fold higher in the PCOS group. The fasting glucose to insulin ratio was lower in the PCOS group versus the control group (1.9+/- 0.3 vs 3.1+/-0.3, P =.02). During the hyperinsulinemic-euglycemic clamp, insulin sensitivity was lower in the PCOS group (1.4+/-0.2 vs 2.7+/-0.3 mg/kg/min per microu/mL, P =.002). During the hyperglycemic clamp, insulin secretion was significantly higher in the PCOS group. Insulin sensitivity correlated negatively with fasting insulin (r = -0.71, P =.0002) and positively with the fasting glucose to insulin ratio (r = 0.79, P<.0001). CONCLUSION Adolescent girls with PCOS have profound metabolic derangements detected early in the course of the syndrome, including (1) approximately 50% reduction in peripheral tissue insulin sensitivity, (2) evidence of hepatic insulin resistance, and (3) compensatory hyperinsulinemia. These observations may predict an increased risk of type 2 diabetes mellitus in adolescents with PCOS.
Cervical pedicle screw fixation in 100 cases of unstable cervical injuries: pedicle axis views obtained using fluoroscopy.

OBJECT The authors conducted a study to introduce the imaging technique in which pedicle axis views are obtained using fluoroscopy to match the screw entry point with pedicle orientation and to report the clinical results and safety of cervical pedicle screw fixation (PSF) in patients treated for unstable cervical injuries. METHODS One hundred consecutive patients with unstable cervical injuries underwent PSF in which the authors used fluoroscopic imaging to acquire pedicle axis views. There were 87 men and 13 women whose mean age was 42.5 years. The accuracy of PS placement was examined postoperatively using axial computed tomography (CT) and oblique radiography. Screw malpositioning was classified either as screw exposure (< 50% of the screw outside the pedicle) or pedicle perforation (> 50% of the screw outside the pedicle boundaries). The mean operative time was 97.6 minutes, and the mean estimated blood loss was 221 ml. Local vertebral alignment around the injured segment measured 6.0 degrees of kyphosis preoperatively and 6.7 degrees of lordosis postoperatively. Solid posterior bone fusion was achieved in all but three patients who died shortly after surgery. There was no secondary dislodgment of instrumentation in 95% of these 97 cases. Of the 419 cervical PSs, 43 (10.3%) were of the screw-exposure type and 17 (4.0%) of the pedicle-perforation type. There were two surgery-related complications: one penetration of a probe into the vertebral artery and one radiculopathy. There were six postoperative complications: two cases of instrumentation failure associated with loss of correction, three cases of correction loss (> 10 degrees), and one case of deep wound infection. CONCLUSIONS Solid posterior fusion without secondary dislodgment of hardware was demonstrated in 95% of the cases. The incidence of complications associated with cervical PSF was not high. Postoperative CT scanning showed that 17 (4.0%) of 419 screws perforated the pedicle. It appears that fluoroscopy performed using pedicle axis views improves the accuracy and safety of cervical PS insertion.
Proteome mapping of overexpressed membrane-enriched and cytosolic proteins in sodium antimony gluconate (SAG) resistant clinical isolate of Leishmania donovani.

AIMS This study aimed to identify differentially overexpressed membrane-enriched as well as cytosolic proteins in SAG sensitive and resistant clinical strains of L. donovani isolated from VL patients which are involved in the drug resistance mechanism. METHODS The proteins in the membrane-enriched as well as cytosolic fractions of drug-sensitive as well as drug-resistant clinical isolates were separated using two-dimensional gel electrophoresis and overexpressed identified protein spots of interest were excised and analysed using MALDI-TOF/TOF. RESULTS Six out of 12 overexpressed proteins were identified in the membrane-enriched fraction of the SAG resistant strain of L. donovani whereas 14 out of 18 spots were identified in the cytosolic fraction as compared with the SAG sensitive strain. The major proteins in the membrane-enriched fraction were ABC transporter, HSP-83, GPI protein transamidase, cysteine-leucine rich protein and 60S ribosomal protein L23a whereas in the cytosolic fraction proliferative cell nuclear antigen (PCNA), proteasome alpha 5 subunit, carboxypeptidase, HSP-70, enolase, fructose-1,6-bisphosphate aldolase, tubulin-beta chain have been identified. Most of these proteins have been reported as potential drug targets, except 60S ribosomal protein L23a and PCNA which have not been reported to date for their possible involvement in drug resistance against VL. CONCLUSION This study for the first time provided a cumulative proteomic analysis of proteins overexpressed in drug resistant clinical isolates of L. donovani indicating their possible role in antimony resistance of the parasite. Identified proteins provide a vast field to be exploited for novel treatment strategies against VL such as cloning and overexpression of these targets to produce recombinant therapeutic/prophylactic proteins.
Performance Characteristics of the BDProbeTec System for Direct Detection of Mycobacterium tuberculosis Complex in Respiratory Specimens

ABSTRACT Strand displacement amplification (SDA) technology has been established in a fully automated system known as BDProbeTec. Target sequences of the insertion sequence IS6110 and the 16S rRNA gene are simultaneously amplified, which thus allows the detection of Mycobacterium tuberculosis complex and, as an additional option, of most Mycobacterium species. Detection occurs via a chemiluminescent microwell assay that employs the simultaneous hybridization and capture of SDA products with a biotinylated capture probe and an alkaline phosphatase detector probe. We have evaluated the performance of the BDProbeTec system in detecting M. tuberculosis complex by testing 799 respiratory specimens and comparing the results to those obtained by conventional diagnostic techniques, i.e., microscopy and culture (solid and radiometric media). M. tuberculosis was cultivated from 41 specimens, of which 28 (68.4%) were smear positive and 13 (31.6%) were smear negative. The overall sensitivity of the SDA assay was 97.6% (for smear-positive specimens, 100%; for smear-negative specimens, 92.3%), and specificity was 95.0%. After resolution of the discrepancies by studying the patients’ clinical data, sensitivity and specificity were 97.9 and 96.5%, respectively, and positive and negative predictive values were 63.9 and 99.9%, respectively. These preliminary data demonstrate that the BDProbeTec system has promising performance characteristics with respiratory specimens and that it allows the detection of M. tuberculosis complex within hours.
Secretion and gene expression of inhibin, oxytocin and steroid hormones during the in vitro differentiation of bovine granulosa cells.

Bovine granulosa cells were cultured under defined conditions to examine (1) their secretion of immunoreactive inhibin, oxytocin, progesterone and oestradiol during differentiation in vitro; (2) their expression, by Northern analysis, of specific mRNAs for inhibin and oxytocin as compared with uncultured cells; (3) possible interrelationships between the four secreted hormones; and (4) the hypothesis that androgens and steroidogenesis influence the secretion of inhibin. The secretion of inhibin and oestradiol fell rapidly over the first few days of culture but remained at detectable levels for at least 7 days. Conversely, the secretion of oxytocin and progesterone rose steadily as culture progressed. These changes occurred spontaneously (i.e. without gonadotrophin treatment) and were not dependent on the addition of serum to the culture medium. Messenger RNAs for the inhibin alpha- and beta A-subunits were present in uncultured cells but barely detectable or undetectable in cells cultured for 4 days. Conversely, the mRNA for oxytocin, which was not detectable in uncultured cells, was present in cultured cells and increased in quantity as culture progressed. Treatment of cells with testosterone (5 nM-5 microM), in the presence or absence of serum (10% FCS), had no effect on the secretion of inhibin but stimulated the declining oestradiol secretion. Treatment with ascorbic acid (0.5 mM) increased the secretion of oxytocin and progesterone, as previously described, but not that of inhibin. Treatment with aminoglutethimide (0.5 mM), an inhibitor of steroidogenesis, substantially inhibited progesterone secretion and the response of oestradiol secretion to testosterone, but had no effect on the secretion of either inhibin or oxytocin. We conclude that bovine granulosa cells differentiate spontaneously in defined culture in a manner that, as defined by the secretion of steroid and peptide hormones, closely resembles their luteinization in vivo. The switch in protein hormone secretion from inhibin to oxytocin is accompanied by a corresponding change in mRNA expression. The changes in steroid and peptide hormone secretions that take place in culture appear to occur independently of one another although their absolute cause remains to be determined. In contrast to previous studies, we could find no evidence for the regulation of inhibin secretion by either androgens or steroidogenesis.
Aberrant expression of β‐catenin discriminates acute myeloid leukaemia from acute lymphoblastic leukaemia

The role of β‐catenin in epithelial neoplasms has been widely studied whereas current knowledge regarding β‐catenin gene and protein expression in bone marrow cells derived from normal haematopoiesis and clonal haematological disorders is lacking. β‐Catenin gene expression was quantitatively investigated in bone marrow cells derived from clonal haematological disorders [acute myeloid leukaemia (AML), acute lymphoblastic leukaemia (ALL), Philadelphia chromosome‐positive chronic myeloid leukaemia (Ph+ CML], Ph− myeloproliferative disorders, n = 96) compared with non‐neoplastic haematopoiesis (n = 33) by real‐time reverse transcription polymerase chain reaction. Cellular localization of β‐catenin protein was detected by immunocytochemistry. β‐Catenin gene expression was significantly increased in AML compared with ALL cases (P < 0·0001), Ph+ CML (P < 0·0001) and non‐neoplastic haematopoiesis (P = 0·019). Immunocytochemistry revealed that, in non‐neoplastic haematopoiesis, the granulopoietic lineage as well as megakaryocytes showed membranous and cytoplasmic staining to various degrees along with unlabelled nuclei. Besides haematopoiesis, β‐catenin prominently marked bone marrow vascularity and diverse stroma cells. β‐Catenin gene was inversely expressed in AML and ALL with a lack of protein expression in neoplastic cells in ALL. In contrast, the other haematological disorders under study, except for Ph+ CML, did not show significant alterations of overall β‐catenin gene expression compared with normal bone marrow. These data suggest different regulatory mechanisms in the expression and function of β‐catenin in haematopoietic cells.
Permanent pacemaker selection and subsequent survival in elderly Medicare pacemaker recipients.

BACKGROUND Dual-chamber pacemakers have been in use for more than 15 years. Although they may confer a physiological advantage over single-chamber ventricular pacemakers, they are more expensive and have a generally shorter service life than single-chamber devices. We carried out the present study to identify patient subgroups who were preferentially receiving greater or lesser proportions of dual-chamber devices and to determine whether the selection of different types of pacemakers was associated with differences in mortality. METHODS AND RESULTS We analyzed a 20% random national sample of all Medicare beneficiaries aged 65 years or older who underwent initial placement of a permanent pacemaker and were discharged in 1988, 1989, or 1990 (n = 36,312). The minimum follow-up for vital status was 1 year. The relation of pacemaker type to patient and provider characteristics was determined using logistic regression analysis. The relation between pacemaker type and mortality was determined using the Cox proportional hazards method. The proportion of dual-chamber systems that were received increased from 27.2% in 1988 to 37.0% in 1990 (P < .001). Dual-chamber pacemaker recipients were younger (P < .001) than ventricular pacemaker recipients. Other independent correlates of dual-chamber pacemaker selection included male sex (odds ratio and 95% confidence intervals, 1.18 and 1.12 to 1.24, respectively), atrioventricular block (1.59 and 1.51 to 1.67), congestive heart failure (1.14 and 1.08 to 1.20), atrial fibrillation (0.36 and 0.34 to 0.39), and the presence of a major noncardiac diagnosis (0.86 and 0.83 to 0.89). Nonmedical predictors of dual-chamber pacemaker selection included Medicaid eligibility (0.78 and 0.71 to 0.86), implantation in the western United States (1.19 and 1.10 to 1.29), implantation by a rural provider (0.70 and 0.65 to 0.76), hospitalization in a 500-bed-or-larger hospital (1.20 and 1.13 to 1.28), hospitalization in a private hospital (1.19 and 1.10 to 1.28), or hospitalization in a hospital with a catheterization laboratory (1.47 and 1.38 to 1.56). Dual-chamber pacemaker selection was an independent predictor of survival at 1 year (0.82 and 0.77 to 0.87) and at 2 years (0.82 and 0.77 to 0.87) after controlling for potentially confounding patient-level and hospital-level characteristics. CONCLUSIONS The present study describes important variations in the clinical practice of cardiac pacing, many of which are not based on clinical characteristics. Furthermore, the selection of a dual-chamber pacemaker is associated with increased survival. These results underscore the need for prospective, outcome-based clinical trials of pacemaker mode selection.
Cutbacks revisited: the relationship between resources and performance

ABSTRACT This article investigates the effects of staffing and employee cutbacks in public safety agencies in the context of county governments in California, Texas, and Florida (2002–2014). Although resources have been regarded as one of the most important determinants of performance, we argue that the potential endogeneity and the autoregressive nature of public service performance should be considered to clarify the relationship between resources and performance. This study provides evidence of the inverted-U shape relationship between employee cutbacks and performance, implying that the initial benefit of cutbacks is subject to diminishing returns, and eventually degrades performance.