Miracle-dz/UniFAR-FTUs huggingface dataset:
Molecular Determinants within the Surface Proteins Involved in the Pathogenicity of H5N1 Influenza Viruses in Chickens

ABSTRACT Although it is established that the cleavage site and glycosylation patterns in the hemagglutinin (HA) play important roles in determining the pathogenicity of H5 avian influenza viruses, some viruses exist that are not highly pathogenic despite possessing the known characteristics of high pathogenicity (i.e., their HA contains multiple basic amino acids at the cleavage site and has glycosylation patterns similar to that of the highly pathogenic H5 viruses). Currently little is known about the H5N1 viruses that fall into this intermediate category of pathogenicity. We have identified strains of H5N1 avian influenza viruses that have markers typical of high pathogenicity but distinctly differ in their ability to cause disease and death in chickens. By analyzing viruses constructed by reverse-genetic methods and containing recombinant HAs, we established that amino acids 97, 108, 126, 138, 212, and 217 of HA, in addition to those within the cleavage site, affect pathogenicity. Further investigation revealed that an additional glycosylation site within the neuraminidase (NA) protein globular head contributed to the high virulence of the H5N1 virus. Our findings are in agreement with previous observations that suggest that the activities of the HA and NA proteins are functionally linked.
Comparison of Wechsler Memory Scale–Fourth Edition (WMS–IV) and Third Edition (WMS–III) dimensional structures: Improved ability to evaluate auditory and visual constructs

Dimensional structures underlying the Wechsler Memory Scale–Fourth Edition (WMS–IV) and Wechsler Memory Scale–Third Edition (WMS–III) were compared to determine whether the revised measure has a more coherent and clinically relevant factor structure. Principal component analyses were conducted in normative samples reported in the respective technical manuals. Empirically supported procedures guided retention of dimensions. An invariant two-dimensional WMS–IV structure reflecting constructs of auditory learning/memory and visual attention/memory (C1 = .97; C2 = .96) is more theoretically coherent than the replicable, heterogeneous WMS–III dimension (C1 = .97). This research suggests that the WMS–IV may have greater utility in identifying lateralized memory dysfunction.
Melanoma stem cells: targets for successful therapy?

Increasing evidence suggests that cancer is a disease in which the persistence of the tumor relies on a small population of tumor‐initiating cells, the so called tumor stem cells (TSC). Only these cells are capable of self‐renewal and thereby possess the ability for unlimited proliferation. One reason for the inability of conventional tumor treatments to achieve long‐term cures seems to be that TSC are resistant to many therapeutic approaches. A detailed characterization of TSC should have a substantial impact on the optimization of therapeutic protocols. While TSC in hematopoietic malignancies have been most intensively studied, subpopulations with stem cell properties have been identified in some solid tumors including breast carcinomas, gliomas and melanomas. In case of melanoma, however, a clear‐cut molecular characterization is still pending. Considerable research is needed to establish standard procedures for the isolation of melanoma stem cells to facilitate determining how these cells, critical for tumor persistence and progression, can be effectively eliminated. A pressing question is if melanoma stem cells are in principle sensitive to immunotherapy.
Increased frequency of angiotensin-converting enzyme DD genotype in patients with type 2 diabetes in Taiwan.

BACKGROUND Diabetes is one of the major causes of end-stage renal failure in the Taiwanese population. Previous studies have shown that angiotensin-converting enzyme (ACE) inhibitor can improve glucose utilization and suppress hepatic glucose production and the renin-angiotensin system may play an important role in the initiation and progression of diabetic nephropathy. Thus, ACE gene polymorphism may be associated with type 2 diabetes and diabetic nephropathy. METHODS To investigate the distribution of ACE-I/D genotype in type 2 diabetes and diabetic nephropathy, we examined 336 patients with type 2 diabetes (157 without nephropathy and 179 with nephropathy) and 263 age-matched normal controls. The diagnosis of nephropathy was made when daily protein loss exceeded 500 mg. ACE gene polymorphism was analysed by use of polymerase chain reaction. RESULTS Our study revealed that the frequency of the D allele of the ACE gene was 29.3% in normal controls. The frequency of ACE DD genotype was significantly higher in type 2 diabetics compared with normal controls (18.2 vs 9.1%, P<0.01). The frequency of ACE DD genotype in patients with diabetic nephropathy was significantly higher than in patients without nephropathy (22.3 vs 13.4%, P<0.05). To determine whether ACE gene polymorphism was associated with the severity of diabetic nephropathy, we divided patients with diabetic nephropathy into dialysis and non-dialysis groups. The frequency of ACE DD genotype in the dialysis group was significantly higher than in non-dialysis group (28.7 vs 15.3%, P<0.05). CONCLUSION Our results indicate that the frequency of ACE DD genotype is markedly higher in patients with type 2 diabetes, and the ACE DD genotype is significantly associated with diabetic nephropathy.
Going with the flow: the role of ocean circulation in global marine ecosystems under a changing climate

Ocean warming, acidification, deoxygenation and reduced productivity are widely considered to be the major stressors to ocean ecosystems induced by emissions of CO2. However, an overlooked stressor is the change in ocean circulation in response to climate change. Strong changes in the intensity and position of the western boundary currents have already been observed, and the consequences of such changes for ecosystems are beginning to emerge. In this study, we address climatically induced changes in ocean circulation on a global scale but relevant to propagule dispersal for species inhabiting global shelf ecosystems, using a high‐resolution global ocean model run under the IPCC RCP 8.5 scenario. The ¼ degree model resolution allows improved regional realism of the ocean circulation beyond that of available CMIP5‐class models. We use a Lagrangian approach forced by modelled ocean circulation to simulate the circulation pathways that disperse planktonic life stages. Based on trajectory backtracking, we identify present‐day coastal retention, dominant flow and dispersal range for coastal regions at the global scale. Projecting into the future, we identify areas of the strongest projected circulation change and present regional examples with the most significant modifications in their dominant pathways. Climatically induced changes in ocean circulation should be considered as an additional stressor of marine ecosystems in a similar way to ocean warming or acidification.
Human AlkB Homolog 1 Is a Mitochondrial Protein That Demethylates 3-Methylcytosine in DNA and RNA*

The Escherichia coli AlkB protein and human homologs hABH2 and hABH3 are 2-oxoglutarate (2OG)/Fe(II)-dependent DNA/RNA demethylases that repair 1-methyladenine and 3-methylcytosine residues. Surprisingly, hABH1, which displays the strongest homology to AlkB, failed to show repair activity in two independent studies. Here, we show that hABH1 is a mitochondrial protein, as demonstrated using fluorescent fusion protein expression, immunocytochemistry, and Western blot analysis. A fraction is apparently nuclear and this fraction increases strongly if the fluorescent tag is placed at the N-terminal end of the protein, thus interfering with mitochondrial targeting. Molecular modeling of hABH1 based upon the sequence and known structures of AlkB and hABH3 suggested an active site almost identical to these enzymes. hABH1 decarboxylates 2OG in the absence of a prime substrate, and the activity is stimulated by methylated nucleotides. Employing three different methods we demonstrate that hABH1 demethylates 3-methylcytosine in single-stranded DNA and RNA in vitro. Site-specific mutagenesis confirmed that the putative Fe(II) and 2OG binding residues are essential for activity. In conclusion, hABH1 is a functional mitochondrial AlkB homolog that repairs 3-methylcytosine in single-stranded DNA and RNA.
The diverse roles of IRF4 in late germinal center B‐cell differentiation

Summary: Interferon regulatory factor 4 (IRF4) is a member of the IRF family of transcription factors and is expressed in most cell types of the immune system. Within the B‐cell lineage, IRF4 is expressed in all developmental stages except during the germinal center (GC) reaction. IRF4 expression, however, is upregulated during exit from the GC reaction and has been demonstrated to have critical functions in at least three key developmental processes: the termination of the GC B‐cell transcriptional program, immunoglobulin (Ig) class switch recombination (CSR), and plasma cell development. Herein, we attempt to reconcile the often contradictory findings regarding IRF4 into a model to explain the role of IRF4 in the transcription factor networks that operate within exiting GC B cells. In addition, a deregulation of the biological programs controlled by IRF4 has recently been implicated in the pathogenesis of various B‐cell–derived malignancies. Determining the specific functions of IRF4 in the markedly diverse developmental processes that coordinate B‐cell development is therefore likely to have important implications for understanding these malignancies and devising therapeutic interventions.
The current place of tranexamic acid in the management of bleeding

There has been an explosion of interest in the ability of tranexamic acid to reduce morbidity and mortality in surgical and traumatic bleeding. Tranexamic acid has been shown to reduce mortality due to traumatic bleeding by a third, without apparent safety issues. It is now clearly established that intravenous tranexamic acid reduces blood loss in patients with surgical bleeding and the need for transfusion. It can also be used topically to reduce bleeding. Its use is being explored further in large pragmatic trials in traumatic head injury, postpartum haemorrhage and in upper gastro‐intestinal haemorrhage. There are few side effects from the use of tranexamic acid except when administered in high dose where neurological events have been noted, possibly relating to tranexamic acid interfering with cerebral GABA and glycine receptors. However, clinical studies suggest that there is no increased efficacy in using a higher dose, and that a dose of 1 g intravenously in an adult patient has maximal efficacy, which is not increased by higher doses. The CRASH‐2 trauma trial clearly showed no increase in thrombotic events after its use in trauma, indeed there was a significant reduction in myocardial infarction. However, trials of tranexamic acid in surgery have failed to adequately study its effects on the risk of postoperative venous and possible reduction in arterial thrombo‐embolism, and this needs to be the subject of future research.
Financial Vulnerability and Stabilization Policy in Commodity Exporting Emerging Economies

This paper develops a new Keynesian DSGE model compatible with the structural characteristics of commodity exporting developing economies (financial vulnerability, relatively high pass-through rates, procyclical fiscal policy, and high terms of trade volatility) to compare the performance of alternative policy regimes, namely flexible domestic inflation targeting, flexible consumer price index inflation targeting, and the real exchange rate targeting. Evaluation of the above alternative policy regimes and relative stability of key macroeconomic variables are conducted through an optimal Ramsey policy method. The policy evaluation results based both on stabilization and welfare measures obtained for the case of Iran imply that for the developing commodity (oil) exporting economies stabilization with a broader inflation targeting framework in which the real exchange rate is also targeted is the superior policy regime. Optimality of the alternative policy regimes and their rank are sensitive to the degree of financial vulnerability. Financial vulnerability in this model explains why departure from floating exchange rate in an inflation targeting framework is the appropriate policy and not merely a “fear”. As the degree of financial development increases sufficiently, the standard flexible inflation targeting becomes the superior policy regime. A policy rule to weaken procyclicality of fiscal policy further enhances the welfare performance of this regime.
The ketogenic diet as a treatment for traumatic brain injury: a scoping review

ABSTRACT Traumatic brain injury (TBI) is a leading cause of morbidity and mortality worldwide. The ketogenic diet (KD) has been identified as a potential therapy to enhance recovery after TBI. The purpose of this study is to complete a scoping review and synthesize the evidence regarding the KD and its therapeutic effects in TBI. The methodological framework of Arksey and O’Malley was employed. Databases searched include Medline, EMBASE, CCRCT, CINAHL and WebOfScience. Two reviewers independently screened titles, abstracts and full texts in a two-step screening protocol to determine inclusion. Abstracted data included study setting and therapeutic mechanism. The KD was demonstrated to reduce cerebral oedema, apoptosis, improve cerebral metabolism and behavioural outcomes in rodent TBIs. Additionally, the KD affected rodent TBIs in an age-dependent manner. Due to a lack of relevant outcome measures, the human trials did not establish much evidence with respect to the KD as a treatment for TBI; only its safety was established. The KD is an effective treatment for TBI recovery in rats and shows potential in humans. Future research should aim to better elucidate the KD’s mechanisms of action in human TBIs and determine if the KD’s effectiveness on clinical outcomes can be reproduced in humans.
Regulation of HIF prolyl hydroxylases by hypoxia‐inducible factors

Hypoxia and induction of hypoxia‐inducible factors (HIF‐1α and HIF‐2α) is a hallmark of many tumors. Under normal oxygen tension HIF‐alpha subunits are rapidly degraded through prolyl hydroxylase dependent interaction with the von Hippel‐Lindau (VHL) tumor suppressor protein, a component of E3 ubuiquitin ligase complex. Using microarray analysis of VHL mutated and re‐introduced cells, we found that one of the prolyl hydroxylases (PHD3) is coordinately expressed with known HIF target genes, while the other two family members (PHD1 and 2) did not respond to VHL. We further tested the regulation of these genes by HIF‐1 and HIF‐2 and found that siRNA targeted degradation of HIF‐1α and HIF‐2α results in decreased hypoxia‐induced PHD3 expression. Ectopic overexpression of HIF‐2α in two different cell lines provided a much better induction of PHD3 gene than HIF‐1α. In contrast, we demonstrate that PHD2 is not affected by overexpression or downregulation of HIF‐2α. However, induction of PHD2 by hypoxia has HIF‐1‐independent and ‐dependent components. Short‐term hypoxia (4 h) results in induction of PHD2 independent of HIF‐1, while PHD2 accumulation by prolonged hypoxia (16 h) was decreased by siRNA‐mediated degradation of HIF‐1α subunit. These data further advance our understanding of the differential role of HIF factors and putative feedback loop in HIF regulation. Published 2004 Wiley‐Liss, Inc.
Accounting Education for Professional Accountants: Evidence from Italy

In the last years, the worldwide changes in global, political and financial contexts have gradually modified the approaches to the accounting of national governments and international institutions. In this varying scenario, the International Accounting Standard Board (IASB) and consequently national governments have introduced new accounting standards along with related regulatory changes. These issues are of ever-growing importance when considering that the International Accounting Education Standards Board (IAESB) has recently developed “The basis for conclusions document for 2017-2021 IAESB Strategy and 2017-2018 Work Plan” (IAESB, 2017) with the aim of informing the Board’s deliberations on its future strategy and priorities about the future expectations of professional competence. The aim of this paper is to report the findings of an empirical study on this topic and address the following research question: what are professional accountants’ views on quality in accounting education? This primary research question is expanded to consider professional accountants’ beliefs on the present (what is necessary for their workplace) and future (what will be necessary for their workplace) with respect to quality in accounting education. The survey highlights how professional accountants have more expectations than in the past about their skills. The majority of professional accountants have been transforming themselves into business consultants since they are now required to offer more services than accounting and taxation consultancy. Consequently, there is a growing demand for cooperation with the university world in order to broaden the programs of accounting education with new technical competencies for undergraduate and postgraduate degrees.
Differences in change scores and the predictive validity of three commonly used measures following concussion in the middle school and high school aged population.

BACKGROUND A battery of tests is commonly used to measure disability with and recovery from concussion. A number of different concussion-oriented assessment tests exist and each is considered useful. To the authors' knowledge, no study has compared the scores of these tests during recovery in the middle school and high school aged population to see how each change over time. PURPOSE The purposes of this study were to analyze clinical data of concussed middle school and high school aged athletes to determine the concurrent and predictive validity for post-concussion syndrome (PCS) of the Post-Concussion Symptom Scale (PCSS), Balance Error Scoring System (BESS), and the five subscales of the Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT). METHODS The study was a retrospective chart review performed on middle school and high school aged individuals with a diagnosis of concussion from the years 2008-2010 within the Akron Children's Hospital Sports Medicine system. To be eligible for inclusion in the dataset, each subject required a baseline measurement for each of the three tests (and all five subscales of the ImPACT) and a post-test measure. The mean age of the population was 15.38 years (SD = 1.7) and ranged from 11 to 19 years. Pearson product correlation tests (correlation matrix) were used to analyze the concurrent validity of the test items during recovery following a concussion. Receiver operating characteristics (ROC) curves were used to determine the predictive validity of initial scores for developing PCS. RESULTS The correlation matrix captured five statistically significant findings; however, these suggested only weak to mild correlations. Five test items yielded an area under the curve (AUC) greater than 0.50 but only one was statistically significant. After qualitative evaluation, only one of the three tests (including the five subscales of the ImPACT) was useful in predicting post-concussion syndrome. CONCLUSION This study suggests that there is poor concurrent validity among three commonly used concussion tests and there is no baseline score that predicts whether post-concussion syndrome will occur. LEVEL OF EVIDENCE 2b.
Tropical forests and the changing earth system

Tropical forests are global epicentres of biodiversity and important modulators of the rate of climate change. Recent research on deforestation rates and ecological changes within intact forests, both areas of recent research and debate, are reviewed, and the implications for biodiversity (species loss) and climate change (via the global carbon cycle) addressed. Recent impacts have most likely been: (i) a large source of carbon to the atmosphere, and major loss of species, from deforestation and (ii) a large carbon sink within remaining intact forest, accompanied by accelerating forest dynamism and widespread biodiversity changes. Finally, I look to the future, suggesting that the current carbon sink in intact forests is unlikely to continue, and that the tropical forest biome may even become a large net source of carbon, via one or more of four plausible routes: changing photosynthesis and respiration rates, biodiversity changes in intact forest, widespread forest collapse via drought, and widespread forest collapse via fire. Each of these scenarios risks potentially dangerous positive feedbacks with the climate system that could dramatically accelerate and intensify climate change. Given that continued land-use change alone is already thought to be causing the sixth mass extinction event in Earth's history, should such feedbacks occur, the resulting biodiversity and societal consequences would be even more severe.
Antitumor Activity of Prosopis glandulosa Torr. on Ehrlich Ascites Carcinoma (EAC) Tumor Bearing Mice

The antitumor activity of ethanol extract of Prosopis glandulosa Torr. (EPG) was evaluated against Ehrlich ascites carcinoma (EAC) tumor model in Swiss albino mice on dose dependent manner. The activity was assessed using survival time, average increase in body weight, hematological parameters and solid tumor volume. Oral administration of EPG at the dose of 100, 200 and 400 mg/Kg, significantly (p < 0.001) increased the survival time and decreased the average body weight of the tumor bearing mice. After 14 days of inoculation, EPG was able to reverse the changes in the hematological parameters, protein and PCV consequent to tumor inoculation. Oral administration of EPG was effective in reducing solid tumor mass development induced by EAC cells. The results indicate that EPG possess significant antitumor activity on dose dependent manner.
Studying the Effect of Sertraline in Reducing Aggressive Behavior in Patients with Major Depression

Purpose: Depression causes dysfunction in various spheres of individual and social life, which is now considered as the fourth-leading cause of the global disease burden. Given that violence and aggression associated with depression in the community cause serious damage to the family, the prediction, early detection and effective treatment of aggressive and violent behavior are essential. The present study compared the severity of aggression before and after treatment with sertraline in patients with major depression. Methods: This is an intervention type study and the study population consisted of patients with depression and aggression. The sampling included 23 eligible patients. Data were obtained by SCID-I, SCID-II, STAXI-II, BDI-II and was also analyzed using SPSS 23 software. Results: The results showed that depression, anger mood, desire to verbally express anger, controlling anger and anger control before treatment was reduced but the desire for physical expression of anger increased. Conclusion: Obtained results in this research support the effect of Sertraline on reduction of severity of depression, reduction of severity of symptoms of aggression and anger (state of anger, anger feeling, and the tendency to express anger verbally), increased controlling external anger and significantly controlling internal anger. Hence, Sertraline can be found effective in the treatment of patients with depression and aggressive behaviors. Also Sertraline increases tend to cause physical representation of anger, then this issue supports the increase in the euthanasia behavior in primary days of treatment with SSRI that requires more assessments.