Miracle-dz/UniFAR-FTUs huggingface dataset:
Impact of JAK2V617F Mutational on Haematologic Features in Sudanese Patients with Essential Thrombocythemia and Thrombotic Risk Assessment

Objective: We correlated selected hematological parameters in Sudanese essential thrombocythemia (ET) patients based on their homozygous/heterozygous JAK2V617F genotype, as well as the application of thrombotic risk assessment using different thrombotic risk scoring models. Methods: In this single-center study, we evaluated 60 patients with ET at the time of the diagnosis without any prior treatment. Amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) technique was used to determine JAK2V617F mutation status. Complete blood count was evaluated using the Sysmex analyzer. Furthermore, the thrombotic risk assessment of ET patients using different thrombotic risk scoring models was applied. Results: The JAK2V617F mutation was detected in 29/60 patients (48.3%), of whom 23 (38.3% of total) were heterozygous and 6 (10.0%) were homozygous. Compeered to JAK2 wild-type or JAK2 heterozygous patients, JAK2 homozygous patients for JAK2V617F mutation were associated with older age(p<0.05), significantly higher mean leukocytes count (P =0.001), significantly lower Hb concentration (p<0.05), and splenomegaly (p<0.05), while the mean of the platelet counts was slightly higher, although not reached a significant level. We also found two patients who developed thrombotic events throughout follow-up and Journal of Bioscience and Applied Research, 2020, Vol.6, No. 4, P.263 -273 pISSN: 2356-9174, eISSN: 2356-9182 264 were initially classified as a low-risk category in the traditional classification. One of them with age < 60 years, hypertension, and JAK2 homozygosity but without thrombosis history, was allocated in a high-risk category by IPSET-t and rIPSET-t scores. The second patient was stratified in a low-risk category by all scoring models with age < 60 years, hypertension, leukocytosis, unmutated JAK2, and without a history of thrombosis. Conclusions: The JAK2 V617F homozygosity correlated with older age, higher leukocyte count, lower Hb concentration, and a higher risk of thrombosis in Sudanese ET patients. Evaluation of hypertension and identification of JAK2 V617F homozygosity at diagnosis of ET might give the clinician more meaningful prognostic information and so improve the therapeutic management.
Hypoxia and mesenchymal stromal cells as key drivers of initial fracture healing in an equine in vitro fracture hematoma model

Fractures in horses–whether simple fractures with just one clean break, or incomplete greenstick with stress fractures, or complications such as shattered bones can all be either minimal or even catastrophic. Thus, improvement in fracture healing is a hallmark in equine orthopedics. The fracture healing process implements a complex sequence of events including the initial inflammatory phase removing damaged tissue, re-establishment of vessels and mesenchymal stromal cells, a soft and hard callus phase closing the fracture gap as well as the remodeling phase shaping the bone to a scar-free tissue. Detailed knowledge on processes in equine fracture healing in general and on the initial phase in particular is apparently very limited. Therefore, we generated equine in vitro fracture hematoma models (FH models) to study time-dependent changes in cell composition and RNA-expression for the most prominent cells in the FH model (immune cells, mesenchymal stromal cells) under conditions most closely adapted to the in vivo situation (hypoxia) by using flow cytometry and qPCR. In order to analyze the impact of mesenchymal stromal cells in greater detail, we also incubated blood clots without the addition of mesenchymal stromal cells under the same conditions as a control. We observed a superior survival capacity of mesenchymal stromal cells over immune cells within our FH model maintained under hypoxia. Furthermore, we demonstrate an upregulation of relevant angiogenic, osteogenic and hypoxia-induced markers within 48 h, a time well-known to be crucial for proper fracture healing.
Bank Credit and Market-Based Finance for Corporations: The Effects of Minibond Issuances

We study the effects of the diversification of funding sources on the financing conditions for firms. We exploit a regulatory reform which took place in Italy in 2012, i.e., the introduction of “minibonds”, which opened a new market-based funding opportunity for unlisted firms. Using the Italian Credit Register, we investigate the impact of minibond issuance on bank credit conditions for issuer firms, both at the firm-bank and firm-level. We compare new loans granted to issuer firms with new loans concurrently granted to similar non-issuer firms. We find that issuer firms obtain lower interest rates on bank loans of the same maturity than non-issuer firms, suggesting an improvement in their bargaining power with the banks. In addition, issuer firms reduce the amount of used bank credit but increase the overall amount of available external funds, pointing to a substitution with bank credit and to a diversification of corporate funding sources. Studying their ex-post performance, we find that issuer firms expand their total assets and fixed assets, and also raise their leverage.
Cortisol and adrenal androgens as independent predictors of mortality in septic patients

Objective To determine the prognostic value of cortisol, Dehydroepiandrosterone (DHEA) and Dehydroepiandrosterone-sulfate (DHEAS), together with their ratios (cortisol/DHEA and cortisol/DHEAS), as independent predictors of mortality in septic patients. Methods Prospective cohort study of 139 consecutive patients with a diagnosis of severe sepsis or septic shock. Adrenal hormones were determined within the first 24 hours of the septic process. To determine and compare the predictive ability of each marker for the risk of unfavorable evolution (in-hospital, 28-day and 90-day mortality), ROC (Receiver Operating Characteristic) curves were constructed and the area under the curve (AUC) was determined. As measures of association, adjusted odds ratios (OR) with their 95% confidence intervals (95%CI) were estimated by unconditional logistic regression. Cortisol, DHEA and DHEAS results were compared to lactate, CRP, SOFA and APACHE II Scores. Results Cortisol showed the best predictive ability, with AUCs of 0.758, 0.759 and 0.705 for in-hospital mortality, and 28-day and 90-day mortality, respectively; whereas AUCs for 28 days mortality for SOFA and APACHE II scores, and other biomarkers studied, such as Lactate or CRP, were 0.644, 0.618, 0.643 and 0.647, respectively. Associations between high cortisol levels (>17.5 μg/dL) and mortality were strong and statistically significant for in-hospital and 28-day mortality: adjusted ORs 10.13 and 9.45 respectively, and lower for long term mortality (90 days): adjusted OR 4.26 (95% CI 1.34–13.56), p trend 0.014. Regarding adrenal androgens, only positive associations were obtained for DHEAS and most of these positive associations did not yield statistical significance. Regarding Cortisol/DHEA and cortisol/DHEAS ratios, they did not improve the predictive ability of cortisol. The only exception was the cortisol/DHEAS ratio, which was the best predictor of mortality at 90 days (AUC 0.737), adjusted OR for highest cortisol/DHEAS ratio values 6.33 (95%CI 1.77–22.60), p trend 0.002. Conclusion Basal cortisol measured within the first 24 hours of the septic process was the best prognostic factor for in-hospital and 28-day mortality, even superior to the Sequential Organ Failure Assessment (SOFA) or Acute Physiology and Chronic Health Evaluation II (APACHE II) scores. The cortisol/DHEAS ratio was an independent predictor of long-term mortality.
Childhood trauma and the impact of deployment on the development of mental disorder in military males

Abstract Background Childhood adversity is associated with mental disorder following military deployment. However, it is unclear how different childhood trauma profiles relate to developing a post-deployment disorder. We investigated childhood trauma prospectively in determining new post-deployment probable disorder. Methods In total, 1009 Regular male ADF personnel from the Australian Defence Force (ADF) Middle East Area of Operations (MEAO) Prospective Study provided pre- and post-deployment self-report data. Logistic regression and generalised structural equation modelling were utilised to examine associations between childhood trauma and new post-deployment probable disorder and possible mediator pathways through pre-deployment symptoms. Results There were low rates of pre-deployment probable disorder. New post-deployment probable disorder was associated with childhood trauma, index deployment factors (combat role and deployment trauma) and pre-deployment symptoms but not with demographic, service or adult factors prior to the index deployment (including trauma, combat or previous deployment). Even after controlling for demographic, service and adult factors prior to the index deployment as well as index deployment trauma, childhood trauma was still a significant determinant of new post-deployment probable disorder. GSEM demonstrated that the association between interpersonal childhood trauma and new post-deployment probable disorder was fully mediated by pre-deployment symptoms. This was not the case for those who experienced childhood trauma that was not interpersonal in nature. Conclusions To determine the risk of developing a post-deployment disorder an understanding of the types of childhood trauma encountered is essential, and pre-deployment symptom screening alone is insufficient
Silibinin induced apoptosis of human epidermal cancer A431 cells by promoting mitochondrial NOS

Abstract The antitumor effects of silibinin are of increasing interest, though its mechanism is not yet clear. The goal of this study was to clarify the mechanism of silibinin-induced cell death in the A431 human epidermoid carcinoma cell line. We used a cell viability assay, flow cytometry, nitric oxide (NO) assay, and western blotting to examine relationships between silibinin, NO generation and apoptosis in A431 cells. Silibinin inhibited A431 cell growth in a dose-dependent manner, inducing mitochondrial damage, and apoptosis at a high dose. At the same time, high dose silibinin increased NO levels in A431 cells and the endothelial nitric oxide synthase (eNOS) inhibitor NG-nitro-L-arginine methylester (L-NAME) attenuated silibinin-induced cell growth inhibition. By western blotting, silibinin caused increased eNOS phosphorylation in the mitochondria. The AMP-activated protein kinase inhibitor compound C significantly decreased p-eNOS expression, while blocking eNOS did not affect p-AMPK levels, suggested that AMPK acted upstream of eNOS. This study showed that silibinin increased NO levels in A431 cells by activating the AMPK–eNOS pathway, leading to mitochondrial dysfunction and apoptosis. In this mechanism of action, mitochondrial eNOS played an important role. The results provided new understanding of the functions of intracellular NO.
The Role of Insulators in Transgene Transvection in Drosophila

Precise activity of a gene requires its promoter to be matched with an appropriate enhancer. Insulators are DNA elements which can limit inappropriate enhancer-promoter interactions. More recently, their ability to stimulate gene activity has been also recognized. Transvection is the phenomenon where a transcriptional enhancer activates a promoter located on the homologous chromosome. It has been amply documented in Drosophila where homologs are closely paired in most, if not all, somatic nuclei, but it has been known to rarely occur in mammals as well. We have taken advantage of site-directed transgenesis to insert reporter constructs into the same genetic locus in Drosophila and have evaluated their ability to engage in transvection by testing many heterozygous combinations. We find that transvection requires the presence of an insulator element on both homologs. Homotypic trans-interactions between four different insulators can support transvection: the gypsy insulator (GI), Wari, Fab-8 and 1A2; GI and Fab-8 are more effective than Wari or 1A2. We show that, in the presence of insulators, transvection displays the characteristics that have been previously described: it requires homolog pairing, but can happen at any of several loci in the genome; a solitary enhancer confronted with an enhancerless reporter is sufficient to drive transcription; it is weaker than the action of the same enhancer-promoter pair in cis, and it is further suppressed by cis-promoter competition. Though necessary, the presence of homotypic insulators is not sufficient for transvection; their position, number and orientation matters. A single GI adjacent to both enhancer and promoter is the optimal configuration. The identity of enhancers and promoters in the vicinity of a trans-interacting insulator pair is also important, indicative of complex insulator-enhancer-promoter interactions.
Alternariol as virulence and colonization factor of Alternaria alternata during plant infection

The filamentous fungus Alternaria alternata is a potent producer of many toxic secondary metabolites, which contaminate food and feed. The most prominent one is the polyketide‐derived alternariol (AOH) and its derivative alternariol monomethyl ether (AME). Here, we identified the gene cluster for the biosynthesis of AOH and AME by CRISPR/Cas9‐mediated gene inactivation of several biosynthesis genes in A. alternata and heterologous expression of the gene cluster in Aspergillus oryzae. The 15 kb‐spanning gene cluster consists of a polyketide synthase gene, pksI, an O‐methyltransferase, omtI, a FAD‐dependent monooxygenase, moxI, a short chain dehydrogenase, sdrI, a putative extradiol dioxygenase, doxI and a transcription factor gene, aohR. Heterologous expression of PksI in A. oryzae was sufficient for AOH biosynthesis. Co‐expression of PksI with different tailoring enzymes resulted in AME, 4‐hydroxy‐alternariol monomethyl ether (4‐OH‐AME), altenusin (ALN) and altenuene (ALT). Hence, the AOH cluster is responsible for the production of at least five different compounds. Deletion of the transcription factor gene aohR led to reduced expression of pksI and delayed AOH production, while overexpression led to increased expression of pksI and production of AOH. The pksI‐deletion strain displayed reduced virulence on tomato, citrus and apple suggesting AOH and the derivatives as virulence and colonization factors.
Effects of Timing of Umbilical Cord Clamping on Preventing Early Infancy Anemia in Japanese Term Infants With Planned Breastfeeding: A Randomized Controlled Trial

BackgroundJapanese infants have relatively higher risk of anemia and neonatal jaundice. This study aimed to assess the effects of delayed cord clamping (DCC) on the prevention of anemia during early infancy in Japanese term infants with planned exclusive breastfeeding for 4 months. This study also aimed to explore the effects of DCC on neonatal jaundice.Methods We conducted an open-label, parallel-arm, multicenter randomized controlled trial of DCC (clamping the cord after more than a minute or pulsation stops) vs. early cord clamping (ECC; clamping the cord within 15 sec) at one birth center and two clinics in Japan. Pregnant women planning to have a vaginal birth and to exclusively breastfeed and term singleton infants delivered in cephalic presentation were included in this study. The primary outcome was spectrophotometric estimation of hemoglobin at 4 months. Secondary outcomes were anemia incidence at four months, four outcomes related to neonatal jaundice, hematocrit levels, and related outcomes. ResultsA total of 150 pregnant women were recruited. Participants (N = 138) were randomly allocated to two groups (DCC n= 68, ECC n = 70). There were no significant differences between the two groups in spectrophotometric estimation of hemoglobin at 4 months: mean difference = 0.1 g/dL, 95% confidence interval -0.14, 0.35, DCC 12.4 g/dL, ECC 12.3 g/dL. Only the hematocrit levels on days 3 to 5 were significantly higher in the DCC group than in the ECC group: DCC 57.0%, ECC 52.6%, mean difference = 4.4, 95% confidence interval 2.61, 6.20. There were no significant differences in other secondary outcomes, including outcomes related to neonatal jaundice.ConclusionAmong Japanese term infants with planned exclusive breastfeeding, DCC showed no significant effects on spectrophotometric hemoglobin levels at 4 months compared with ECC. We observed significantly higher hematocrit levels in infants who underwent DCC, while these levels were within the normal range. Jaundice outcomes remained similar to those of infants who underwent ECC. Although a larger sample size is required to assess the effects of cord clamping on neonatal jaundice, DCC may prevent anemia in newborn infants.Trial registration: UMIN-CTR; UMIN000022573, 06/01/2016 - retrospectively registered, https://upload.umin. ac.jp/cgi-open-bin/ctr/ctr_view. cgi? recptno=R000023056
Characterization and identification of flavonoids from Bambusa chungii leaves extract by UPLC-ESI-Q-TOF-MS/MS

Bamboo leaves extract (BLE) has a variety of physiological functions such as antitumour, anti-inflammatory, antioxidant and blood fat reduction activities and the flavonoids of bamboo leaves are the major active constituents. To profile the flavonoids in the complex BLE, a rapid and sensitive analytical method based on ultra-high-performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight tandem mass spectrometry (UPLC-ESI-Q-TOF-MS/MS) was developed for the structural identification of the flavonoids in Bambusa chungii leaves extract using accurate mass measurements and characteristic fragmentation patterns. After separation on an Agilent SB-C18 Rapid Resolution High Definition (RRHD) column (2.1 mm × 150 mm, 1.8 μm) by gradient elution with 0.1% formic acid aqueous solution and acetonitrile as the mobile phase, the sample was analysed by ESI-QTOF-MS/MS in the negative mode. A total of 22 flavonoids were detected, and eight of these were identified by comparison with reference standards, while the other fourteen were tentatively identified according to their MS/MS data. The main fragmentation pathways of flavonoid C-glycosides (compounds 1, 5 and 10), flavonoid di-C,O-glycosides (compound 4), flavonoid di-C-glycosides (compound 7) and flavonoid C,O-di-glycosides (compounds 2 and 14) are shown in this article. This is the first report on the analysis of the flavonoids in the extract of B. chungii leaves. The present work demonstrates that UPLC-ESI-Q-TOF-MS/MS is an efficient technique for identifying multiple flavonoids of BLE.
Self-esteem and aggression in women: differences between female prisoners and women without criminal records

ABSTRACT Contradictory findings have been reported regarding the association between self-esteem and aggression. Most studies have dealt with non-criminal populations. This study aimed to explore the relationship between self-esteem and aggression and investigate possible differences in self-esteem and aggression between female inmates and women without criminal records (non-criminals) in the prefecture of Attica, Greece. One hundred fifty-seven female inmates in the Attica’s Korydallos Female Prison and 150 non-criminals from Attica’s general population completed the Buss & Perry Aggression Questionnaire and Rosenberg’s Self-esteem Scale between February 2012 and April 2014. Lower self-esteem was associated with higher aggression among women independent of criminality. Self-esteem was lower in inmates (Mean = 18.06, SD = 6.19) than in non-criminals (Mean = 21.65, SD = 4.90, p < .001). Female prisoners presented higher aggression than non-criminals (unadjusted Mean = 78.40, SD = 23.60 versus Mean = 68.82, SD = 14.95, p < .001). However, after adjusting for age, education and self-esteem, this difference was no longer statistically significant (p = .127). Further studies, especially in female offenders, should be conducted to broaden our understanding of female aggression with a view to developing and promoting focused therapeutic procedures.
Anxiety and depression aggravate impulsiveness: the mediating and moderating role of cognitive flexibility

ABSTRACT Empirical research suggested that individuals with anxiety and/or depression exhibited action on the spur of the moment, with little consideration for the consequences of their actions. However, it remains unclear whether the precise mechanisms underlying the impacts of anxiety and depression on impulsivity. The present study examined how anxiety and depression influence impulsivity, as well as the mediating and moderating role of cognitive flexibility. A sample of 477 Chinese university students was recruited. All participants finished self-report measures of anxiety, depression, impulsivity, and cognitive flexibility. No significant gender difference was found in anxiety, depression, cognitive flexibility, and three subscale scores of impulsivity. Greater scores of anxiety and depression were associated with lower scores of cognitive flexibility and higher levels of impulsivity. Depression and cognitive flexibility could predict attention impulsivity and nonplanning impulsivity, while anxiety and cognitive flexibility could predict motor impulsivity. Cognitive flexibility served as a mediator in the links of anxiety and three subscales of impulsivity. Furthermore, cognitive flexibility moderated the impact of anxiety on motor impulsivity.
FDG-PET/CT in managing infection in patients with hematological malignancy: clinician knowledge and experience in Australia

Abstract PET/CT is useful for investigation of neutropenic fever (NF) and potential invasive fungal infection (IFI) in those with hematological malignancies (HM). An online survey evaluating the utility and current practices regarding PET/CT scanning for investigation of NF was distributed to infectious diseases (ID) clinicians and hematologists via email lists hosted by key professional bodies. One-hundred and forty-five clinicians responded (120 ID; 25 hematologists). Access to PET/CT was fair but timeliness of investigation was limited (within 3 days in 35% and 46% of ID and hematology respondents, respectively). Among those with experience with PET/CT for infection (n = 109), 40% had utilized PET/CT for prolonged NF and 20% for diagnosing IFI. The majority of respondents indicated the desire to utilize PET/CT more frequently for infection indications. There is a strong desire among surveyed Australian clinicians to use PET/CT for prolonged NF and potential IFI. However, access to PET/CT is a current barrier to uptake.