Miracle-dz/UniFAR-FTUs huggingface dataset:
Evaluation of the cytotoxic response mediated by perforin and granzyme B in patients with non-Hodgkin lymphoma

Abstract This study quantified the perforin and granzyme B in patients with non-Hodgkin lymphoma (NHL) at the time of diagnosis. Protein quantification was performed by flow cytometry. NHL patients had a higher number of cytotoxic T lymphocytes (CTLs) expressing perforin as well as a greater number of activated CTLs than the control group. However, intracellular perforin levels in natural killer cells were lower in the NHL patients compared to the control group. Quantitative real time PCR showed that patients had more expression of perforin and granzyme B transcripts compared to the control group. In addition, patients who had expression of both genes below the median found for the NHL group had lower survival rates. Considering this, we believe that perforin and granzyme B are potential prognostic markers in NHL and thus it is fundamental to pay attention to their expressions in these patients.
Transcriptional Regulation of Chitin Synthases by Calcineurin Controls Paradoxical Growth of Aspergillus fumigatus in Response to Caspofungin

ABSTRACT Attenuated activity of echinocandin antifungals at high concentrations, known as the “paradoxical effect,” is a well-established phenomenon in Candida albicans and Aspergillus fumigatus. In the yeast C. albicans, upregulation of chitin biosynthesis via the protein kinase C (PKC), high-osmolarity glycerol response (HOG), and Ca2+/calcineurin signaling pathways is an important cell wall stress response that permits growth in the presence of high concentrations of echinocandins. However, nothing is known of the molecular mechanisms regulating the mold A. fumigatus and its paradoxical response to echinocandins. Here, we show that the laboratory strain of A. fumigatus and five of seven clinical A. fumigatus isolates tested display various magnitudes of paradoxical growth in response to caspofungin. Interestingly, none of the eight strains showed paradoxical growth in the presence of micafungin or anidulafungin. Treatment of the ΔcnaA and ΔcrzA strains, harboring gene deletions of the calcineurin A subunit and the calcineurin-dependent transcription factor, respectively, with high concentrations of caspofungin revealed that the A. fumigatus paradoxical effect is calcineurin pathway dependent. Exploring a molecular role for CnaA in the compensatory chitin biosynthetic response, we found that caspofungin treatment resulted in increased chitin synthase gene expression, leading to a calcineurin-dependent increase in chitin synthase activity. Taken together, our data suggest a mechanistic role for A. fumigatus calcineurin signaling in the chitin biosynthetic response observed during paradoxical growth in the presence of high-dose caspofungin treatment.
Prevalence and distribution of the use of medicated glasses and refractive errors among Nigerian youths in a tertiary institution in Rivers State Nigeria

The use of medicated glasses as visual aids was associated with the elderly,but in recent times the population of younger people using medicated glasses is alarming.Academic excellence is dependent on a number of factors of which clear comfortable binocular vision is dominant. Genetic, cultural and environmental factors play key roles in the prevalence and distribution of refractive errors. This study estimated the prevalence and distribution of the use of medicated glasses and refractive errors among students of Madonna University Nigeria, Elele campus, Rivers state. One thousand (1000) questionnaires were randomly distributed to 3 year undergraduate students in various departments in the college of medicine, including Anatomy, Physiology, Medicallab. Science, Optometry, Public health, and Pharmacy. 852 (85.2%) of the questionnaires were retrieved and analyzed using simple percentages. Data collected included information on age, sex, state of origin, place of residence and presence of refractive errors. Our results reveal that North-west region had the highest prevalence of the use of medicated glasses among youths at 61.29%. This is followed by south-west (55.67%), southsouth (36.27%), south-east (31.67%), north-central (19.67%) and north-east (15.79%). On the average, the prevalence of the use of medicated glasses is 41.20% in the Southern part and 32.25% in the Northern part of Nigeria. The incidence of refractive errors also followed the same trend with North-west having (93.55%), South-west (50.51%), South-south (32.88%), South-east (27.67%), North central (18.03%) and North-east (15.79%). The highest occurring refractive error among the six geopolitical regions of Nigeria is myopia (54%), followed by hyperopia (21.01%), astigmatism (15.30%) and presbyopia (9.46%). This work represents the first attempt at having a comprehensive outlook at the statistics of the use of medicated glasses among Nigerian youths as well as the incidence of refractive errors among Nigerian youths.
Judging the DSGE Model by Its Forecast

We study the forecasting ability of the standard estimated medium scale dynamic stochastic general equilibrium model. We show that although over the Great Moderation period the model forecasts have good relative forecasting ability, in an absolute sense their forecasting ability is poor. However, we argue that average forecasting ability during the Great Moderation is not a good metric to judge a model’s validity given that this is a period that is well-known to be characterized by a lack of persistent fluctuations in the data. We then consider the forecast performance of the DSGE model prior to the Great Moderation – a period that is known to be characterized by persistent and thereby forecastable fluctuations in the data generating process – and find notably better absolute forecasting performance. We then offer alternative ways of using forecasts to judge the empirical validity of the model. In particular, we suggest that looking at whether the model captures well the forecastability versus nonforecastability of the data upon which the model is estimated is a more fitting question than simply whether the model forecasts well. As part of the empirical analysis that we undertake to address our key questions, we also uncover and document the importance of data and sample choices in the model’s forecasting ability. ---VERY PRELIMINARY AND VERY INCOMPLETE-----PLEASE DO NOT CITE---
A systematic review of the association between depression and health care utilization in children and adults with sickle cell disease

Patients with sickle cell disease (SCD) experience a disproportionately high use of health care resources. Several studies have examined depression and other negative mood states as risk factors for increased health care utilization; however, there have been no systematic reviews examining and summarizing this evidence in SCD. The aim of this systematic review, therefore, was to determine whether depression or depressive symptoms are associated with health care utilization among children and adults with SCD. We followed a quantitative systematic review protocol based on the Preferred Reporting Items for Systematic Reviews and Meta‐ Analyses guidelines and performed a literature search of records from January 1980 to April 2014 using six databases. Empirical studies were eligible if the sample was primarily composed of patients with SCD and included data on depression, mood disorder diagnosis or depressive symptoms and health care utilization. We included 12 studies involving 54 036 unique participants. The prevalence estimates for depression ranged from 2–57%. Seven studies found a significant, or marginally significant, association between depression and utilization while five did not. Patients reporting depression had an estimated 2·8 times greater relative risk of being a high utilizer, and 2·9 versus 1·8 hospitalizations per year on average compared to patients without depression. Overall, depressive symptoms are common in SCD and may increase risk for poor outcomes including health care utilization. The available studies on depression in SCD, however, are limited by small sample sizes, retrospective designs or short follow‐up. This systematic review found a modest association between depression and health care utilization in SCD.
In Defense of Limited Manufacturing Cost Control: Disciplining Acquisition of Private Information by Suppliers

When a firm's input supplier can acquire and misreport private information to gain an edge in negotiations, we show that the firm can blunt the supplier's informational advantage by permitting inefficiencies in its own internal production. Specifically, we establish that a modest increase in the cost of the input(s) a firm makes internally credibly commits it to be more aggressive in negotiations with a supplier for the input(s) the firm buys. Recognizing that its potential information rents will be limited, the supplier, in turn, becomes less aggressive in information acquisition. The paper fully characterizes the equilibrium - the firm's investments, the supplier's information acquisition and reporting decisions, and the terms of trade - to demonstrate that often-maligned internal bloat can be an endogenous facilitator of efficient outsourcing.
Downregulation of miR-23a and miR-27a following Experimental Traumatic Brain Injury Induces Neuronal Cell Death through Activation of Proapoptotic Bcl-2 Proteins

MicroRNAs (miRs) are small noncoding RNAs that negatively regulate gene expression at the post-transcriptional level. To identify miRs that may regulate neuronal cell death after experimental traumatic brain injury (TBI), we profiled miR expression changes during the first several days after controlled cortical impact (CCI) in mice. miR-23a and miR-27a were rapidly downregulated in the injured cortex in the first hour after TBI. These changes coincided with increased expression of the proapoptotic Bcl-2 family members Noxa, Puma, and Bax. In an etoposide-induced in vitro model of apoptosis in primary cortical neurons, miR-23a and miR-27a were markedly downregulated as early as 1 h after exposure, before the upregulation of proapoptotic Bcl-2 family molecules. Administration of miR-23a and miR-27a mimics attenuated etoposide-induced changes in Noxa, Puma, and Bax, reduced downstream markers of caspase-dependent (cytochrome c release and caspase activation) and caspase-independent (apoptosis-inducing factor release) pathways, and limited neuronal cell death. In contrast, miRs hairpin inhibitors enhanced etoposide-induced neuronal apoptosis and caspase activation. Importantly, administration of miR-23a and miR-27a mimics significantly reduced activation of Puma, Noxa, and Bax as well as attenuated markers of caspase-dependent and -independent apoptosis after TBI. Furthermore, miR-23a and miR-27a mimics significantly attenuated cortical lesion volume and neuronal cell loss in the hippocampus after TBI. These findings indicate that post-traumatic decreases in miR-23a and miR-27a contribute to neuronal cell death after TBI by upregulating proapoptotic Bcl-2 family members, thus providing a novel therapeutic target.
Unusual Presentation of Meckel's Diverticulum

leiomyosarcoma (Yang et al. 1965). Secondary spread has been described from stomach (Ahmed & Beasley 1979) and from bladder (Powell & Jones 1983). Phimosis of the prepuce of the clitoris has seldom been reported (Kramarosky & Manriquez 1975), but has not been reported in the postpubertal female. It may be, however, that this is a condition which will be seen more frequently in association with the wearing of tight trousers by young women.
A familial hemorrhagic trait associated with a deficiency of a clot-promoting fraction of plasma.

Recently, three patients have been studied in whom the clotting time of venous blood was greatly prolonged. None of the patients had significant hemorrhagic symptoms. The trait was apparently familial and appeared in both sexes. The patients' disorder could not be identified with any known bleeding disease. However, in each case, the plasma was deficient in a substance found in normal globulin which accelerated the clotting of normal, platelet-deficient plasma. This clot-promoting fraction, present in heated, barium sulfate-adsorbed serum, was neither thrombic nor thromboplastic and did not alter the rate of conversion of fibrinogen to fibrin by thrombin, nor of prothrombin to thrombin by tissue thromboplastin. By inference, its effect was upon an earlier stage of clotting, presumably upon the development of thromboplastic activity in shed blood. However, the fraction did not appear to contain any of the components of plasma known to be necessary for the optimal evolution of plasma thromboplastic activity. The characteristics of the clot-promoting fraction, deficient in the plasma of these three patients, suggests that its properties may be identical with those of an unidentified accelerator of clotting described in an earlier study (1). Tentatively, until its mode of action becomes clear, this fraction may be named Hageman factor, after Patient I.
Emerging role of S-1 in gastric cancer

Abstract Gastric cancer remains one of the most important malignancies worldwide in terms of incidence and mortality. The treatment is based on the combination of local surgery and radiation therapy as well as systemic chemotherapy and targeted molecules. Fluoropyrimidines and particularly 5-fluorouracil (FU) represent still the backbone for gastric cancer chemotherapy and new molecular versions of this molecule have been brought to clinical practice in order to improve benefits and reduce adverse effects. S-1 is an oral prodrug of 5-FU, which has demonstrated high effectiveness for gastric cancer treatment and a favorable safety profile. Currently, there are geographic differences in the treatment of gastric cancer and in the use of S-1, which is a mainstay of gastric cancer management in Eastern countries, but is not part of the standard care in the rest of the world. In this review, we gathered data from phase I, II, and III trials of S-1 in gastric cancer, in order to define its real benefit-risk ratio and assess whether geographic differences in S-1 use are justified by unchangeable factors.
The Research on the Factors of Purchase Intention for Fresh Agricultural Products in an E-Commerce Environment

Based on the characteristics of e-commerce of fresh agricultural products in China, and using the correlation analysis method, the relational model between product knowledge, perceived benefit, perceived risk and purchase intention is constructed. The Logistic model is used to carry in the empirical analysis. The influence factors and the mechanism of online purchase intention are explored. The results show that consumers’ product knowledge, perceived benefit and perceived risk can affect their purchase intention. Consumers’ product knowledge has a positive effect on perceived benefit and perceived benefit has a positive effect on purchase intention. Consumers’ product knowledge has a negative effect on perceived risk, and perceived profit has a negative effect on perceived risk, and perceived risk has a negative effect on purchase intention. Through the empirical analysis, some feasible suggestions for the government and electricity supplier enterprises can be provided.
Parental Involvement with the Criminal Justice System and the Effects on Their Children: A Collaborative Model for Researching Vulnerable Families

Despite the existing body of research examining the effects of imprisonment on incarcerated adults, as of yet, there is no solid empirical evidence for understanding the effects of parental involvement with the criminal justice system involvement (CJSI) on children and families. Accordingly, Columbia University-New York State's Child Psychiatric Epidemiology Group (CPEG), supported by a strong collaboration with The Bronx Defenders, a holistic public defender providing free legal representation, is conducting a longitudinal study examining the effects of parental involvement with the criminal justice system on this population. The study aims to understand, over time, the impact of parental CJSI on their children's mental health, including the effects of the collateral legal damage of CJSI (such as eviction and deportation), substance use, the development of risky behaviors leading to the child's potential involvement with the criminal justice system, as well as protective factors and identification of potential intervention points, which has the ability to inform public policy.
S‐adenosyl methionine regulates ubiquitin‐conjugating enzyme 9 protein expression and sumoylation in murine liver and human cancers

Ubiquitin‐conjugating enzyme 9 (Ubc9) is required for sumoylation and is overexpressed in several malignancies, but its expression in hepatocellular carcinoma (HCC) is unknown. Hepatic S‐adenosyl methionine (SAMe) levels decrease in methionine adenosyltransferase 1A (Mat1a) knockout (KO) mice, which develop HCC, and in ethanol‐fed mice. We examined the regulation of Ubc9 by SAMe in murine liver and human HCC, breast, and colon carcinoma cell lines and specimens. Real‐time polymerase chain reaction and western blotting measured gene and protein expression, respectively. Immunoprecipitation followed by western blotting examined protein‐protein interactions. Ubc9 expression increased in HCC and when hepatic SAMe levels decreased. SAMe treatment in Mat1a KO mice reduced Ubc9 protein, but not messenger RNA (mRNA) levels, and lowered sumoylation. Similarly, treatment of liver cancer cell lines HepG2 and Huh7, colon cancer cell line RKO, and breast cancer cell line MCF‐7 with SAMe or its metabolite 5′‐methylthioadenosine (MTA) reduced only Ubc9 protein level. Ubc9 posttranslational regulation is unknown. Ubc9 sequence predicted a possible phosphorylation site by cell division cycle 2 (Cdc2), which directly phosphorylated recombinant Ubc9. Mat1a KO mice had higher phosphorylated (phospho)‐Ubc9 levels, which normalized after SAMe treatment. SAMe and MTA treatment lowered Cdc2 mRNA and protein levels, as well as phospho‐Ubc9 and protein sumoylation in liver, colon, and breast cancer cells. Serine 71 of Ubc9 was required for phosphorylation, interaction with Cdc2, and protein stability. Cdc2, Ubc9, and phospho‐Ubc9 levels increased in human liver, breast, and colon cancers. Conclusion: Cdc2 expression is increased and Ubc9 is hyperphosphorylated in several cancers, and this represents a novel mechanism to maintain high Ubc9 protein expression that can be inhibited by SAMe and MTA. (HEPATOLOGY 2012;56:982–993)
Role of Knowledge Management in Empowerment of Agriculture Organization’s Experts in Ilam Province, Iran

The purpose of this research was to determine knowledge management in the empowerment of the experts of Agricultural Organization in Ilam County of Iran. The statistical population was composed of all employees with the organizational positions of expert or higher in Agricultural Organization of Ilam (N=150). A self-designed questionnaire was used as data collection tool whose face and content validities were confirmed by a panel of experts and whose reliability was estimated to be 0.89 by Cronbach’s alpha. Data were analyzed by SPSS20 in two groups of descriptive statistics (frequency, percentage, mean, standard deviation, and coefficient of variations) and inferential statistics (Spearman test of correlation and multiple regression analysis). Results of regression analysis showed positive, significant relationship of knowledge exchange, knowledge generation, and number of training courses with people’s empowerment so that they, together, accounted for 40% of the variations of dependent variable.
Strategic Disclosure and Debt Covenant Violation

This study examines how managers change their forecasting behavior as a debt covenant violation (DCV) approaches. We find that management forecasts are more optimistic in the quarter before a DCV, and this result is stronger when firms face a higher risk of shifting control rights to lenders in the event of a DCV. Furthermore, we find that managers combine their forecast optimism with actions that are favorable to shareholders but would likely be curtailed by lenders after the DCV. Lastly, we find managers who are more optimistic in their forecasts are less likely to be replaced after a DCV. Overall, our results are consistent with managers changing their disclosure behavior in an attempt reduce lenders’ awareness of an impending DCV, and thus, buy themselves time to take actions favorable to equity investors.
Regulation of Insulin-Like Growth Factor I Receptor Promoter Activity by Wild-Type and Mutant Versions of the WT1 Tumor Suppressor1.

The insulin-like growth factor I (IGF-I) receptor is a transmembrane tyrosine kinase that mediates the growth-promoting effects of IGF-I and IGF-II. Changes in IGF-I receptor messenger RNA levels are reflected in cell surface receptor number, and modulation of IGF-I receptor levels affects tumorigenicity in numerous cellular models; thus, control of IGF-I receptor gene expression appears to be an important level at which cellular proliferation and tumorigenic potential may be regulated. We have previously shown that the product of the WT1 Wilms' tumor suppressor gene represses IGF-I receptor gene expression both in vitro and in vivo, and that decreased WT1 levels are correlated with up-regulation of IGF-I receptor gene expression in Wilms' tumor, benign prostatic hyperplasia, and breast cancer. Gene regulation by WT1 is complex, in that the WT1 gene encodes a variety of products as a result of alternative splicing and RNA editing, and a number of missense point mutations have been characterized in Wilms' tumor-associated syndromes. Additionally, the WT1 protein has been demonstrated to self-associate through its N-terminal domain, although the role of this intermolecular interaction in transcriptional regulation by WT1 is unclear. In this report, we analyze the relative activity of wild-type and mutant versions of the WT1 protein with respect to IGF-I receptor promoter activity in transient transfection assays and assess the potential contribution of WT1 self-association to IGF-I receptor regulation using the yeast two-hybrid system. Of the naturally occurring variations in WT1 structure, only the presence of a three-amino acid KTS insert in the zinc finger domain introduced by alternative splicing of exon 9 had a significant effect on WT1 repression of IGF-I receptor promoter activity. The N- and C-terminal domains of WT1 also exhibited partial repression, as did the most common mutant version of the WT1 protein associated with Denys-Drash syndrome. Mutations in the WT1 N-terminus attenuated WT1 self-association in the yeast two-hybrid system, but did not impair transcriptional repression. Our results suggest that 1) the DNA-binding capacity of WT1 is critical for maximal repression of the IGF-I receptor promoter, but some effects may be mediated through protein-protein interactions involving the N-terminal domain; 2) WT1 self-association may not be required for repression of the IGF-I receptor promoter; and 3) the Denys-Drash syndrome version of the WT1 protein may exhibit residual or possible gain of function activity in some contexts rather than exerting dominant negative effects, as has been proposed previously.