Miracle-dz/UniFAR-FTUs huggingface dataset:
Male accessory sex organ morphogenesis is altered by loss of function of Hoxd‐13

The role of the Hox gene Hoxd‐13 in postnatal morphogenesis of the male accessory sex organs was examined by correlating the distribution and temporal regulation of expression in the accessory sex organs of postnatal mice with morphologic abnormalities of Hoxd‐13‐deficient transgenic mice. Previous studies of Hoxd‐13 expression in the perinatal period have shown a broad domain of expression in the lower genito‐urinary tract, with expression in both mesenchyme and epithelium; focal expression was also noted in the epithelium of the nascent ducts of the developing prostate. Quantitative RT‐PCR studies of Hoxd‐13 expression in the 5 day mouse confirm widespread expression in the accessory sex organs developing from both the Wolffian duct and the urogenital sinus. Expression is down‐regulated with age, and a detailed time course of expression in the developing prostate shows that the level of Hoxd‐13 expression correlates with morphogenetic activity in the development of the prostate ductal system. Transgenic Hoxd‐13‐deficient mice display multiple abnormalities in the male accessory sex organs. The most severe abnormalities were observed in organs exhibiting ductal branching during postnatal development and included diminished mesenchymal folding in the seminal vesicles, decreased size and diminished ductal branching in the ventral and dorsal prostate, and agenesis of the bulbourethral gland. We conclude that Hoxd‐13 expression in the postnatal period correlates with a period of intense morphogenetic activity in accessory sex organ development and that the function of Hoxd‐13 is evidenced by morphologic abnormalities in accessory sex organs of the Hoxd‐13‐deficient mutant. Dev. Dyn. 208:454–465, 1997. © 1997 Wiley‐Liss, Inc.
The District Role In International Baccalaureate

What is, or could be, the role of the district in the adoption and implementation of IB? To explore that question, researchers from the Institute for Education and Social Policy at NYU selected one site that has earned a reputation success in both participation levels and performance in its school program and as a leader for its role - as a district - in the expansion and support of those programs. Our questions focused on why they made that choice and how they went about implementing it, where they created new structures or supports for schools, and what evidence they point to as markers of success (or pitfalls to avoid). Our hope was to learn by studying what they have learned by doing, and to share what they have learned with other districts and schools.
Orexin receptor antagonism: an ascending multiple-dose study with almorexant

The objectives of this study were to investigate the multiple-dose tolerability, safety, pharmacokinetics, and pharmacodynamics of the dual orexin receptor antagonist almorexant. Healthy subjects received daily doses of almorexant (100, 200, 400 or 1000 mg) or placebo in the morning for four days followed by two days with evening administration (Days 5–6). Each dose level was investigated in a new group of 10 subjects (eight active, two placebo, 1:1 sex). Dose-dependent increases in frequency and intensity were observed for somnolence and other adverse events. Pharmacokinetics at steady state showed rapid absorption, low concentrations eight hours post-dose, and minimal accumulation. Following evening, administration absorption was delayed and Cmax decreased. Almorexant at 400 and 1000 mg administered in the morning reduced vigilance, alertness, visuomotor coordination, and motor coordination assessed in a psychometric test battery. Polysomnography recordings following evening administration showed a trend towards shorter latency to sleep stages 3 and 4, and shorter latency to, and longer time in, rapid-eye-movement sleep at higher doses when compared to placebo. Whether these findings in healthy subjects translate into relevant sleep-enabling effects in insomnia patients needs to be investigated in future studies.
Sphingosine kinase 1 promotes tumour cell migration and invasion via the S1P/EDG1 axis in hepatocellular carcinoma

Sphingosine kinase 1 (SphK1), which phosphorylates sphingosine to sphingosine‐1‐phosphate (S1P), is overexpressed in various types of cancers, and may act as an oncogene in tumorigenesis. However, little is known about the precise role of the SphK1/S1P pathway in human liver cancer, especially regarding the metastasis of hepatocellular carcinoma (HCC).
Prediction of colorectal cancer relapse and survival via tissue RNA levels of matrix metalloproteinase-9.

PURPOSE In this study, we investigated the association between matrix metalloproteinase (MMP)-9 RNA expression in primary colorectal cancer (CRC) and standard clinicopathologic variables and determined whether levels of MMP-9 RNA predict relapse and survival. PATIENTS AND METHODS Tumor and paired normal mucosa specimens from 71 primary CRC patients following resections were assessed. RNA levels were determined via Northern blot hybridization and quantitated with laser densitometry. Results were expressed as tumor/normal mucosa (T/N) fold-increase calculated after normalizing for RNA loading using 28S expression. Statistical analysis was performed using the SAS statistical package procedure. Kaplan-Meier survival curves were compared with the two-sided log-rank test. RESULTS The mean T/N MMP-9 RNA fold-increase was 9.4 +/- 1.0 (mean +/- SE) (P < .001). Overexpression of MMP-9 RNA correlated significantly with status of synchronous distant metastases (M stage) (P = .004) and Dukes' stage (P = .008). A T/N fold-increase of 5.0 was used to discriminate between high (> 5.0) and low (< or = 5.0) T/N MMP-9 expression. High T/N MMP-9 RNA expression was associated with a significantly shorter disease-free (P = .0001) and overall (P = .0002) survival duration. In univariate and multivariate analyses, T/N MMP-9 RNA level was found to be an independent prognostic factor for disease-free survival. CONCLUSION This report provides the first evidence that increased MMP-9 RNA production in primary human CRC may be a powerful, independent predictor of recurrence and outcome.
Credit Default Swap Spreads, Fair Value Spreads, and Interest Rate Dynamics

This paper examines the empirical relationship between credit risk and interest rate risk. We use the credit default swap (CDS) spread as our measure of credit risk. Also, we control for the variation in the fair-value spread that combines multiple sources of default risk, including the market price of risk (Sharpe ratio), the loss given default (LGD), and the expected default frequency (EDF). After taking into account the fair-value spread, a liquidity risk factor, and several proxies for the general state of the macroeconomy, we find that the interest rate surprise factor serves as a robust determinant of CDS spread gyrations in both the full sample and most subsamples organized by industry type and credit rating status. Furthermore, we empirically find that the swap interest rate variables convey material information about CDS spread movements above and beyond the Treasury interest rate variables in the vast majority of 2SLS regressions. These empirical results have important implications for the parameterization of interest rate dynamics in the Monte Carlo simulation of economic capital for a typical bank's credit portfolio.
Expression of glucose transporter‐1 in human gastric carcinoma

Malignant cells show increased glucose uptake in vitro and in vivo, which is believed to be facilitated by glucose transporters (Gluts). Expression of Glut1, one of the Gluts, has been described in malignancies of the esophagus, colon, pancreas, lung, and brain, but to the authors' knowledge the significance of Glut1 expression in human gastric carcinoma has not been elucidated. The objective of the current study was to examine the expression and distribution of Glut1 and its relation to clinicopathologic parameters in patients with gastric carcinoma.
Promoting productive employment in Sub‐Saharan Africa : a review of the literature

This report provides an overview of current research on and knowledge about employment trends and policies in sub-Saharan Africa. Access to productive employment is seen as essential for poverty reduction and the inclusion of the poor in wider society. Productive employment is characterised by a. Sufficient income to permit workers and their dependents a level of consumption above the poverty line; b. Stability of this income over time absence of vulnerability; c. Decent working conditions and working hours. The challenge of African economies lies not so much in open unemployment, as in the quality of employment as defined by earnings, vulnerability and working conditions. Much employment is located in the informalsector, where vulnerability is a serious problem. High youth employment in young populations is another serious challenge. Causes of employment problems include lack of the right kinds of structural change, skill mismatches on the labour market, insufficient attention for SMEs with growth potential and insufficient innovation. The paper discusses a wide range of policies to promote productive employment including trade policies, sectoral policies, innovation policies, population policies and employment and labour market policies. The paper concludes with a discussion of emerging debates and contrasting views with regard to productive employment. It summarises the debates on agricultural led industrial development, resource based industrialisation, emergence of non-traditional exports, employment in labour intensive modern commercial agriculture, the role of manufacturing in growth and employment creation, the exploitation of unlimited supplies of labour, role of FDI and promoting pro-poor innovation in the informal sector.
The IGF Axis and Placental Function

It is well known that the insulin-like growth factor (IGF) axis is an important regulator of foetal growth and in recent years, it has been suggested that the ligands IGF-I and IGF-II may, in part, mediate this effect by promoting proper placental development and function. In other tissues, IGF effects on metabolism, proliferation and differentiation are primarily mediated via IGF binding protein-regulated interaction of IGFs with the type 1 IGF receptor and therefore here, we review the placental expression and postulated role, of each of the IGF axis components and discuss the cellular mechanisms through which these effects are exerted.
Calcifying Human Aortic Smooth Muscle Cells Express Different Bone Alkaline Phosphatase Isoforms, Including the Novel B1x Isoform

Background: Vascular calcification, causing cardiovascular morbidity and mortality, is associated with hyperphosphatemia in chronic kidney disease (CKD). In vitro, phosphate induces transdifferentiation of vascular smooth muscle cells to osteoblast-like cells that express alkaline phosphatase (ALP). In vivo, raised serum ALP activities are associated with increased mortality. A new bone ALP isoform (B1x) has been identified in serum from CKD patients. The present study investigated the different ALP isoforms in calcifying human aortic smooth muscle cells (HAoSMCs). Methods: HAoSMCs were cultured for 30 days in medium containing 5 or 10 mmol/l β-glycerophosphate in the presence or absence of the ALP-specific inhibitor tetramisole. Results: All known bone-specific ALP (BALP) isoforms (B/I, B1x, B1 and B2) were identified in HAoSMCs. β-Glycerophosphate stimulated calcification of HAoSMCs, which was associated with increased BALP isoforms B/I, B1x and B2. Tetramisole inhibited the β-glycerophosphate-induced HAoSMC calcification, which was paralleled by the inhibition of the B1x and B/I, but not the other isoforms. Conclusions: HAoSMCs express the four known BALP isoforms. B/I, B1x and B2 could be essential for soft tissue calcification. B/I and B1x were more affected by tetramisole than the other isoforms, which suggests different biological functions during calcification of HAoSMCs.
Observability Inequality of Backward Stochastic Heat Equations for Measurable Sets and Its Applications

This paper aims to provide directly the observability inequality of backward stochastic heat equations for measurable sets. As an immediate application, the null controllability of the forward heat equations is obtained. Moreover, an interesting relaxed optimal actuator location problem is formulated, and the existence of its solution is proved. Finally, the solution is characterized by a Nash equilibrium of the associated game problem.
Associations of combined polymorphisms of the platelet membrane glycoproteins Ia and IIIa and the platelet-endothelial cell adhesion molecule-1 and P-Selectin genes with IVF implantation failures

Abstract The aim of the study was to investigate the combined impact of the genetic heterogeneity of the glycoproteins Ia (GpIa) and IIIa (GpIIIa) and the platelet-endothelial cell adhesion molecule-1 (PECAM-1) and P-Selectin genes on IVF embryo transfer implantation failures (IVF-ET failures). Sixty nulligravida women with previous IVF-ET failures and 60 fertile controls were genotyped for the GpIa-C807T, GpIIIa-PlA1/PA2, PECAM-1-C373G (Leu125Val) and P-Selectin-A37674C (Thr715Pro) polymorphisms by pyrosequencing. Compared with wild-type combined homozygotes, carriers of combinations of risk alleles in two gene loci were at significantly increased risk for IVF-ET failure, whereas carriers of the combination of GpIa-807T, GpIIIa-PlA2 and PECAM-1-373G alleles had OR = 52.50 (95%CI: 4.05–680.95, p < .001). The area under the receiver-operating characteristic curve (AUC) based on the number of polymorphisms and the number of risk alleles per subject was 75.4% (95%CI: 66.7%–82.8%, p < .001) and 72.5% (95%CI: 63.6%–80.3%, p < .001), respectively. The OR per polymorphism and risk allele increase was 4.26 (95%CI: 2.15–8.41, p < .001) and 2.85 (95%CI: 1.71–4.76, p < .001), respectively. The above associations were more robust among younger women. The combined analysis of these polymorphisms revealed strong association of combined carriers with IVF-ET failures especially for younger women and provided a genetic risk score with good diagnostic accuracy in the prediction of IVF-ET failures.
Intestinal parasitic and candida infection associated with HIV infection in Cameroon.

INTRODUCTION HIV causes progressive impairment of the cellular immune system leading to increased susceptibility to infectious agents. Parasitic infestations are common in HIV-infected patients and usually lead to diarrhoea. Few studies have addressed the issue of intestinal parasites among HIV-infected persons in Cameroon. This investigation was conducted in Douala, Cameroon, to assess the prevalence of gastrointestinal parasites in HIV-infected patients, taking into account their immune status and treatment course. METHODOLOGY Stool and blood samples were collected from 201 HIV-positive patients for the investigation of intestinal pathogens and CD4+ counts. RESULTS Fifty-six (27.9%) patients harbored pathogens. The most frequent pathogens were Candida spp. (14.9%), Cryptosporidium spp. (7.5%), Entamoeba histolytica, and Entamoeba dispar (3%). The presence of pathogens was significantly associated with diarrhoea, as they were found in 48.6% of diarrhoeic stools and 23.2% of non-diarrhoeic stools (OR = 3.14, p= 0.0018). Prevalence of pathogens and diarrhoea were significantly higher in patients with CD4+ counts ≤ 200 cells/µL (OR = 2.17, p = 0.0349 and OR = 8.46, p = 0.000019 respectively). CONCLUSIONS This study highlights the need for investigating intestinal pathogens in HIV-infected patients presenting with diarrhoea, especially when their CD4+ counts are low.
Erector spinae plane block for postoperative analgesia in patients undergoing total abdominal hysterectomy: a randomized controlled study original study

Background: Abdominal hysterectomy is associated with marked postoperative pain and morbidity, but effective postoperative analgesia provides early recovery and ambulation. Aim: We intended to assess the efficacy of bilateral erector spinae plane block (ESPB) on postoperative analgesia in females undergoing abdominal hysterectomy under general anesthesia. Settings and Design: The design was a prospective, randomized, controlled, single-blind clinical study. Patients and Methods: Sixty patients with American Society of Anesthesiologists (ASA) physical status classes Ι to ΙΙΙ were scheduled for elective abdominal hysterectomy under general anesthesia, patients were randomly allocated into two equal groups. ESPB patients received ultrasound-guided ESPB at T9 vertebrae level with 20 ml bupivacaine 0.5%. Control group patients did not receive a block. Total fentanyl consumption in the first 24 h and visual analogue scale (VAS) score for pain were evaluated postoperatively. Unpaired Student’s t-tests, chi-square tests, and Z tests were used to compare groups. Results: No significant differences were recorded between the groups regarding age, weight, ASA physical status, or surgery duration, Total fentanyl consumption in the first 24 h was significantly higher in the control group than the ESPB group (P=0.003; 485±20.39 mcg vs 445±67.49 mcg, respectively), VAS for pain was significantly higher in the control group for the first 12 h postoperatively. Conclusions: Bilateral ESPB provided effective postoperative analgesia and markedly decreased postoperative fentanyl consumption in patients undergoing an abdominal hysterectomy.
A Phase IIa, Randomized, Double-Blind Study of Remimazolam (CNS 7056) Versus Midazolam for Sedation in Upper Gastrointestinal Endoscopy

BACKGROUND:This exploratory study was the first study of remimazolam in patients to assess the safety and efficacy of different single doses for procedural sedation. METHODS:Patients scheduled to undergo a diagnostic upper gastrointestinal endoscopy were randomized to receive 1 of 3 doses of remimazolam or midazolam (25 per group) in a double-blind manner. After a single dose of study drug to achieve sedation, patients underwent gastroscopy. We assessed the success of the procedure, sedation levels, recovery from sedation, and safety. RESULTS:A single dose of remimazolam resulted in a successful procedure in 32%, 56%, and 64% of patients in the low (0.10), middle (0.15), and high (0.20 mg/kg) dose groups compared with 44% of patients in the midazolam (0.075 mg/kg) dose group. The onset of sedation was 1.5 to 2.5 minutes in the remimazolam dose groups compared with 5 minutes for midazolam. Because this was a single administration study, sedation could be maintained for as long as necessary to complete the procedure, using rescue midazolam or propofol. Recovery from sedation was rapid for all treatment groups but was influenced by the choice of rescue medication. There were no obvious differences in the safety profiles of remimazolam and midazolam. CONCLUSIONS:This exploratory dose-finding study showed that a single administration of remimazolam (0.10–0.20 mg/kg) was capable of inducing rapid sedation with a quick recovery profile in patients undergoing a diagnostic upper gastrointestinal endoscopy. The safety profile was favorable and appeared to be similar to that of midazolam, warranting further development of this short-acting compound.
Role of N-terminal domain of streptokinase in protein transport.

Streptokinase (SK), an extracellular protein of several haemolytic strains of Streptococcus, is utilized as a potent thrombolytic agent for the treatment of various myocardial disorders. Functional properties of SK remain unchanged when the first 13 N-terminal amino acid (aa) residues are removed. At present, role of this segment in protein structure function is unclear. skc gene encoding for the mature SK and its deletion variant, lacking its first 13 aa residues, were cloned and expressed in E. coli. Full length SK, deprived of any leader sequences, was able to translocate slowly, across the cyto-plasmic and outer membranes of E.coli. Whereas, SK derivative, devoid of its first 13 N-terminal aa residues, could not do so. Cell fractionation studies as well as genetic evidences utilizing alkaline phosphatase fusion, point towards the existence of additional information for protein transport, within the N-terminal domain of SK. To further investigate the role of this region in protein secretion, genetic fusions were created in between full length and 13 aa deleted SK with OmpA leader peptide. Studies on kinetics of SK export from E.coli, revealed that translocation of protein is 3-4 times faster when the first 13 N-terminal residues of SK are intact. On the basis of results obtained, it has been proposed that the N-terminus of mature SK maintains the export competent status of protein and, thus, confer speed and efficiency upon the translocation process of streptokinase.
Clinical contraindications to allergen immunotherapy: an EAACI position paper

Clinical indications for allergen immunotherapy (AIT) in respiratory and Hymenoptera venom allergy are well established; however, clinical contraindications to AIT are not always well documented. There are some discrepancies when classifying clinical contraindications for different forms of AIT as ‘absolute’ or ‘relative’. EAACI Task Force on ‘Contraindications to AIT’ was created to evaluate and review current literature on clinical contraindications, and to update recommendations for both sublingual and subcutaneous AIT for respiratory and venom immunotherapy. An extensive review of the literature was performed on the use of AIT in asthma, autoimmune disorders, malignant neoplasias, cardiovascular diseases, acquired immunodeficiencies and other chronic diseases (including mental disorders), in patients treated with β‐blockers, ACE inhibitors or monoamine oxidase inhibitors, in children under 5 years of age, during pregnancy and in patients with poor compliance. Each topic was addressed by the following three questions: (1) Are there any negative effects of AIT on this concomitant condition/disease? (2) Are more frequent or more severe AIT‐related side‐effects expected? and (3) Is AIT expected to be less efficacious? The evidence, for the evaluation of these clinical conditions as contraindications, was limited, and most of the conclusions were based on case reports. Based on an extended literature research, recommendations for each medical condition assessed are provided. The final decision on the administration of AIT should be based on individual evaluation of any medical condition and a risk/benefit assessment for each patient.
Neutralizing Antibodies and Pathogenesis of Hepatitis C Virus Infection

Hepatitis C virus (HCV) infection is a major cause of chronic liver disease worldwide. The interplay between the virus and host innate and adaptive immune responses determines the outcome of infection. There is increasing evidence that host neutralizing responses play a relevant role in the resulting pathogenesis. Furthermore, viral evasion from host neutralizing antibodies has been revealed to be an important contributor in leading both to viral persistence in acute liver graft infection following liver transplantation, and to chronic viral infection. The development of novel model systems to study HCV entry and neutralization has allowed a detailed understanding of the molecular mechanisms of virus-host interactions during antibody-mediated neutralization. The understanding of these mechanisms will ultimately contribute to the development of novel antiviral preventive strategies for liver graft infection and an urgently needed vaccine. This review summarizes recent concepts of the role of neutralizing antibodies in viral clearance and protection, and highlights consequences of viral escape from neutralizing antibodies in the pathogenesis of HCV infection.