Miracle-dz/UniFAR-FTUs huggingface dataset:
Insufficient recovery of thymopoiesis predicts for opportunistic infections in allogeneic hematopoietic stem cell transplant recipients

Background Recovery of thymopoiesis after allogeneic hematopoietic stem cell transplantation is considered pivotal for full immune competence. However, it is still unclear to what extent insufficient recovery of thymopoiesis predicts for subsequent opportunistic infections and non-relapse mortality. Design and Methods A detailed survey of all post-engraftment infectious complications, non-relapse mortality and overall survival during long-term follow-up was performed in 83 recipients of allogeneic stem cell grafts after myeloablative conditioning. Recovery of thymopoiesis was assessed using analysis of signal joint T-cell receptor rearrangement excision circles. The impact of recovery of thymopoiesis at 2, 6, 9 and 12 months post-transplantation on clinical outcome beyond those time points was evaluated by univariate and multivariate Cox regression analyses. Results The cumulative incidence of severe infections at 12 months after transplantation was 66% with a median number of 1.64 severe infectious episodes per patient. Patients in whom thymopoiesis did not recover were at significantly higher risk of severe infections according to multivariable analysis. Hazard ratios indicated 3- and 9-fold increases in severe infections at 6 and 12 months, respectively. Impaired recovery of thymopoiesis also translated into a higher risk of non-relapse mortality and outweighed pre-transplant risk factors including age, donor type, and disease risk-status. Conclusions These results indicate that patients who fail to recover thymopoiesis after allogeneic hematopoietic stem cell transplantation are at very high risk of severe infections and adverse clinical outcome.
Identification of Four Fimbria-Encoding Genomic Islands That Are Highly Specific for Verocytotoxin-Producing Escherichia coli Serotype O157 Strains

ABSTRACT Verocytotoxin-producing Escherichia coli causes zoonotic food- or waterborne infection that may be associated with massive outbreaks and with the serious complication of hemolytic uremic syndrome (HUS). Serotypes O157:H7 and O157:NM are more commonly associated with HUS and outbreaks than other serotypes, such as O26:H11. To determine whether a genetic basis exists for why serotype O157:H7/NM causes HUS and outbreaks more often than other serotypes, such as O26:H11, we conducted suppression subtractive hybridization (SSH) between the genomes of the sequenced O157:H7 strain EDL933 and CL1, a clinical serotype O26:H11 isolate. Genes from four EDL933 fimbria-encoding genomic O islands (OIs) (OI-1, -47, -141, and -154) were identified in the SSH library. OI-47 encodes several additional putative virulence factors, including secreted and signaling proteins, a hemolysin locus, a lipoprotein, an ABC transport system, and a lipid biosynthesis locus. The distribution of the OIs was investigated by PCR and Southern hybridization (when PCR was negative) with 69 VTEC strains belonging to 39 different serotypes corresponding to 5 seropathotypes that differ in their disease and epidemic potential. The four OIs described here were distributed almost exclusively in serotypes O157:H7 and O157:NM, which indicates that they may be associated with the ability of these strains to colonize human and/or animal intestinal tracts and to cause epidemic and serious disease more frequently than other serotypes. The occurrence of the four OIs in enteropathogenic E. coli O55:H7 strains is consistent with their vertical inheritance by VTEC O157:H7/NM from this clonally related ancestor.
Employee Voluntary and Involuntary Turnover and Organizational Performance: Revisiting the Hypothesis from Classical Public Administration

ABSTRACT: This article examines the effects of voluntary, involuntary, and absolute turnover rates on organizational performance. Adopting human capital and cost-benefit theories, this article posits that voluntary and involuntary turnover would have a linear negative and an inverted U-shaped relationship with organizational performance, respectively, and that an absolute turnover measure can prevent us from revealing the distinct effects of different types of turnover. Using four years of data from Florida school districts, primary findings suggest that involuntary turnover has an inverted U-shaped relationship with organizational performance, first positive and then negative, while the relationship between voluntary turnover and organizational performance remains inconclusive. The findings also suggest that absolute turnover rates can mask the complex and dissimilar impact that various types of turnover have on organizational performance.
The Intermediate Filament Nestin is Highly Expressed in Normal Human Podocytes and Podocytes in Glomerular Disease

The intermediate protein nestin is expressed in proliferating embryonic tissues and adult tissues undergoing repair. Recently this protein been identified in rodent podocytes. Its role in this cell is unknown, since podocytes are believed to be terminally differentiated and nondividing. We report the first study of nestin in human kidney. Nestin expression in normal mature human glomeruli was confined to podocytes. In developing kidney, nestin was detected in metanephric blastema and in podocytic cells at all stages of glomerular development. Nestin co-localized with vimentin but not with actin or heavy chain myosin IIA, using a mouse podocyte cell line. Knockdown of nestin in a murine podocyte cell line failed to produce any obvious phenotypic change or alteration in vimentin distribution but was associated with increased cell cycling. A survey of glomerular diseases failed to identify any condition lacking nestin, indicating that the protein is critical for some aspect of podocyte function. Perhaps through an association with vimentin, nestin serves to bolster the mechanical strength of these cells that experience high tensile stress during glomerular filtration. Nestin was also expressed in podocytes that are reported to be ‘dysregulated’ (lacking podocyte markers). Thus, nestin has a potential as a reliable podocyte marker, even for podocytes that are not completely differentiated (for example, during development) or ‘dedifferentiated’ in glomerular disease.
MODIFICATION OF ENDORPHIN/ENKEPHALIN ANALGESIA AND STRESS‐INDUCED ANALGESIA BY DIVALENT CATIONS, A CATION CHELATOR AND AN IONOPHORE

1 The possibility that divalent cations may antagonize opiate peptide analgesia and stress‐induced analgesia was examined. 2 Intracerebroventricular injection of low doses of Ca2+, Mn2+ and Mg2+ antagonized β‐endorphin and methionine‐enkephalin analgesia. Ba2+ and Cd2+ were without effect. 3 The ionophore, A23187, significantly antagonized β‐endorphin analgesia and the effect was increased when a low dose of Ca2+ was injected at the same time as the ionophore. 4 Ethylene glycol tetraacetic acid (but not ethylenediamine tetraacetic acid) significantly potentiated endorphin analgesia. 5 Stress‐induced analgesia, as determined by increased tail‐flick latencies following intraperitoneal injection of acetic acid, was effectively antagonized by naloxone, Ca2+ and Mn2+. The frequency of writhing following acetic acid injection was increased by both naloxone and divalent metal ions, again suggesting antagonism of endogenous opiates. 6 These results confirm previous findings indicating that divalent metal ions (and especially Ca2+) may be involved in the actions of opiates.
Respiratory Collapse of the Inferior Vena Cava Reflects Volume Shift and Subsequent Fluid Refill in Acute Heart Failure Syndrome.

BACKGROUND Fluid redistribution rather than fluid accumulation plays an important role in the development of acute heart failure (HF) syndrome. Patients with fluid redistribution develop acute HF without prominent volume overload. We investigated volume status by measuring the diameter of the inferior vena cava (IVC) and examining variations in hemoglobin and hematocrit. METHODSANDRESULTS Seventy-four consecutive patients admitted for acute HF syndrome were analyzed. Blood tests and measurement of IVC diameter after stabilization of respiratory distress were performed on admission and were repeated after 24 h. IVC collapsibility index (IVC-CI) was calculated as (maximum IVC-minimum IVC)/maximum IVC. According to the initial IVC-CI, the patients were divided into the collapse group (IVC-CI ≥0.5: n=34) and the non-collapse group (IVC-CI <0.5: n=40). Initial blood pressure was higher in the collapse group (P<0.001). Although 24-h urine volume did not differ between the groups, hemoglobin (P<0.001) and hematocrit (P<0.001) decreased significantly in the collapse group but not in the non-collapse group after 24 h. Furthermore, IVC-CI significantly decreased in the collapse group after 24 h (P=0.003). CONCLUSIONS In acute HF syndrome, IVC-CI ≥0.5 on admission suggests a volume shift from the central vein into the pulmonary vasculature. Fluid refill occurs within 24 h after admission. This observation could be helpful in selecting strategies for diuretic use. (Circ J 2016; 80: 1171-1177).
Enterocytozoon bieneusi Genotype Nomenclature Based on the Internal Transcribed Spacer Sequence: A Consensus

ABSTRACT. The standard method for determining the genotypes of Enterocytozoon bieneusi is based on the DNA sequence of the internal transcribed spacer (ITS) region of the rRNA gene. There are 81 genotypes with 111 genotype names: 26 genotypes have been identified exclusively in humans, eight have been identified in humans and in other hosts, 27 have been identified exclusively in cattle and pigs, six have been identified exclusively in cats and dogs, and 14 have been identified in miscellaneous hosts. Because none of these genotypes has taxonomic status and therefore do not adhere to the International Code of Zoological Nomenclature regarding naming, some genotypes have received multiple names, each different and in separate publications by different authors. Because of the proliferation of genotypes with overlapping names and multiple hosts the scientific literature has become confusing and difficult to efficiently utilize. To reduce confusion and provide guidance for future publications we tabulated all names, GenBank accession numbers, and author citations and propose that the first published name has precedence and should become the primary name used in all subsequent publications in which genotyping is based on ITS sequencing. In those publications the names and GenBank numbers that were submitted at later dates should also be provided by the authors as synonyms to aid readers and reviewers.
Fresh approaches to antidepressant drug discovery

Introduction: The success of antidepressant research has long been challenged by a limited mechanistic understanding of depression pathogenesis and antidepressant treatment response. Progress in this field has thereby consistently been hindered by a lack of novel conceptual approaches and sophisticated experimental techniques to dissect the highly intricate neurobiology of depression. Using fresh approaches to investigate the cellular and molecular mechanisms underlying depression will thus be vital for discovery of novel antidepressant targets. Areas covered: This article provides an overview of some fundamental problems that depression research is currently facing and critically evaluates how these issues could be addressed by future research. It also discusses novel conceptual and technological advances in the field of neuroscience, particularly in regard to how they may help in providing unprecedented insight into the molecular mechanisms of depression pathogenesis. Expert opinion: Although progress in antidepressant drug discovery has been limited over recent years, modern innovations in neuroscience, molecular biology, genetics and bioinformatics are just beginning to revolutionize depression research and to reveal novel and promising treatment targets. Integrating findings from a range of relevant experimental models and using the most advanced technology will be vital for the future success of antidepressant drug discovery.
Epigenetic Modulation Enhances the Therapeutic Effect of Anti–IL-13Rα2 Antibody in Human Mesothelioma Xenografts

Purpose: The interleukin-13 receptor α2 (IL-13Rα2) is expressed by a variety of human malignant cells. Here, we have examined the constitutive surface expression and the epigenetic regulation of IL-13Rα2 by human mesothelioma. We have also investigated the therapeutic effect of the DNA methylation inhibitor 5-aza-2′-deoxycytidine (5-aza-dC) and anti–IL-13Rα2 monoclonal antibody on mesothelioma xenografts. Experimental Design: Cell surface expression of IL-13Rα2 by various lung carcinomas was analyzed using flow cytometry. Therapeutic effects of anti–IL-13Rα2 and 5-aza-dC were investigated using antibody-dependent cellular cytotoxicity and proliferation assays and by monitoring the survival of mesothelioma-bearing mice. Results: We found that human malignant mesotheliomas expressed surface IL-13Rα2 on their surface and that it was upregulated by treatment with 5-aza-dC. This augmented expression of IL-13Rα2 resulted in growth inhibition of the mesothelioma cells when cocultured with anti-IL-13Rα2 and effector cells, such as splenocytes and peritoneal exudate cells. The growth inhibition of mesothelioma cells was mediated by IFN-γ that was only detected in the supernatant when effector cells were exposed to 5-aza-dC–treated tumors in the presence of anti–IL-13Rα2. Compared with the control or either regimen alone, in vivo administration of anti-IL-13Rα2 in combination with 5-aza-dC significantly prolonged the survival of mice with mesothelioma xenografts. Conclusions: These observations indicate a promising role for IL-13Rα2 as a target for antibody treatment in malignant mesothelioma, and, in combination with epigenetic regulation by a DNA methylation inhibitor, suggest the potential for a novel strategy to enhance therapeutic potency. Clin Cancer Res; 17(9); 2819–29. ©2011 AACR.
Estrogen receptor status by immunohistochemistry is superior to the ligand-binding assay for predicting response to adjuvant endocrine therapy in breast cancer.

PURPOSE Immunohistochemistry (IHC) is a newer technique for assessing the estrogen receptor (ER) status of breast cancers, with the potential to overcome many of the shortcomings associated with the traditional ligand-binding assay (LBA). The purpose of this study was to evaluate the ability of ER status determination by IHC, compared with LBA, to predict clinical outcome-especially response to adjuvant endocrine therapy-in a large number of patients with long-term clinical follow-up. PATIENTS AND METHODS ER status was evaluated in 1,982 primary breast cancers by IHC on formalin-fixed paraffin-embedded tissue sections, using antibody 6F11 and standard methodology. Slides were scored on a scale representing the estimated proportion and intensity of positive-staining tumor cells (range, 0 to 8). Results were compared with ER values obtained by the LBA in the same tumors and to clinical outcome. RESULTS An IHC score of greater than 2 (corresponding to as few as 1% to 10% weakly positive cells) was used to define ER positivity on the basis of a univariate cut-point analysis of all possible scores and disease-free survival (DFS) in patients receiving any adjuvant endocrine therapy. Using this definition, 71% of all tumors were determined to be ER-positive by IHC, and the level of agreement with the LBA was 86%. In multivariate analyses of patients receiving adjuvant endocrine therapy alone, ER status determined by IHC was better than that determined by the LBA at predicting improved DFS (hazard ratios/P = 0.474/.0008 and 0.707/.3214, respectively) and equivalent at predicting overall survival (0.379/.0001 and 0.381/.0003, respectively). CONCLUSION IHC is superior to the LBA for assessing ER status in primary breast cancer because it is easier, safer, and less expensive, and has an equivalent or better ability to predict response to adjuvant endocrine therapy.
Redox Metals in Alzheimer's Disease

Abstract: Redox metals in the brain play many important roles in maintenance of cellular function. The maintenance of their homeostasis is of paramount importance to a number of diseases such as Alzheimer's disease and multiple sclerosis. Iron, copper, and zinc are metals of special interest in the pathogenesis of these disorders. This review will focus primarily on iron.
The Flowering Integrator FT Regulates SEPALLATA3 and FRUITFULL Accumulation in Arabidopsis Leavesw⃞

The transition to flowering involves major changes in the shoot apical meristem and in the fate of existing leaf primordia. Transcripts of the Arabidopsis thaliana flowering-promoting gene FLOWERING LOCUS T (FT) are present in leaf tissue but can also promote flowering when artificially introduced into the meristem. FT may normally act in the leaf and/or the meristem, initiating or constituting a mobile flower-promoting signal. We studied FT-dependent events in the rosette leaf, some of which might precede or mimic events in the meristem and its primordia. We show FT-dependent transcript accumulation of the MADS box transcription factors FRUITFULL (FUL) and SEPALLATA3 (SEP3) in leaves. Abnormally high levels of FT further increase the expression of these genes, leading to morphological changes in the leaves. Loss of the flowering-time gene FD, as well as environmental conditions that delay flowering, reduce FT's effect on leaves via reduced activation of its targets. FUL, SEP3, and APETALA1 accumulation in the meristem is associated with and contributes to the transition to flowering. We propose that FT functions through partner-dependent transcriptional activation of these and as-yet-unknown genes and that this occurs at several sites. Organ fate may depend on both degree of activation and the developmental stage reached by the organ before activation occurs.
Comprehensive computational analysis of chromosome 11

Even before the onset of Human Genome Project in 1990, various research, analysis and experiments was going on human genome. In human genome, approximately 3 billion base pairs are structured in the form of 23 pairs of chromosomes. Chromosome 11 is a chromosome that is rich in disease and has a size of 134 million base pairs. From over 1000 genome web servers, the sequence data for the chromosome 11 has been taken as a (.bam) file. On Chromosome 11, approximately 45 different analyses were performed across various fields and categories, such as determining the sequence quality, over represented sequence, peak model, visualizing BAC end pairs, secondary structure prediction by analyses hydroxyl cleavage sites, GC percentage, studying phenotype and disease associated with respect to chromosome 11. Here, we have analysed the evolutionary relationship by isolating positively selected genes across 6 species; predicted the t-RNA and RNA secondary structures and aligned them discretely with the human genome chromosome 11. All these analyses was done primarily with the help of two tools, 1) Web based program-NEBULA and 2) UCSC genome browser.
Effect of Vitamin E and Omega-3 Fatty Acids on Protecting Ambient PM2.5-Induced Inflammatory Response and Oxidative Stress in Vascular Endothelial Cells

Although the mechanisms linking cardiopulmonary diseases to ambient fine particles (PM2.5) are still unclear, inflammation and oxidative stress play important roles in PM2.5-induced injury. It is well known that inflammation and oxidative stress could be restricted by vitamin E (Ve) or omega-3 fatty acids (Ω-3 FA) consumption. This study investigated the effects of Ve and Ω-3 FA on PM2.5-induced inflammation and oxidative stress in vascular endothelial cells. The underlying mechanisms linking PM2.5 to vascular endothelial injury were also explored. Human umbilical vein endothelial cells (HUVECs) were treated with 50 μg/mL PM2.5 in the presence or absence of different concentrations of Ve and Ω-3 FA. The inflammatory cytokines and oxidative stress markers were determined. The results showed that Ve induced a significant decrease in PM2.5-induced inflammation and oxidative stress. Malondialdehyde (MDA) in supernatant and reactive oxygen species (ROS) in cytoplasm decreased by Ve, while the superoxide dismutase (SOD) activity elevated. The inflammatory cytokines interleukin 6 (IL-6) and tumor necrosis factor α (TNF-α) also reduced by Ve. Moreover, Ω-3 FA played the same role on decreasing the inflammation and oxidative stress. IL-6 and TNF-α expressions were significantly lower in combined Ve with Ω-3 FA than treatment with Ve or Ω-3 FA alone. The Ve and Ω-3 FA intervention might abolish the PM2.5-induced oxidative stress and inflammation in vascular endothelial cells. There might be an additive effect of these two nutrients in mediating the PM2.5-induced injury in vascular endothelial cells. The results suggested that inflammation and oxidative stress might be parts of the mechanisms linking PM2.5 to vascular endothelial injury.
Enhancing the Promise of Drug Repositioning through Genetics

The development of new drugs has become challenging as the necessary investments in time and money have increased while drug approval rates have decreased. A potential solution to this problem is drug repositioning which aims to use existing drugs to treat conditions for which they were not originally intended. One approach that may enhance the likelihood of success is to reposition drugs against a target that has a genetic basis. The multitude of genome-wide association studies (GWASs) conducted in recent years represents a large potential pool of novel targets for drug repositioning. Although trait-associated variants identified from GWAS still need to be causally linked to a target gene, recently developed functional genomic techniques, databases, and workflows are helping to remove this bottleneck. The pre-clinical validation of repositioning against these targets also needs to be carefully performed to ensure that findings are not confounded by off-target effects or limitations of the techniques used. Nevertheless, the approaches described in this review have the potential to provide a faster, cheaper and more certain route to clinical approval.