Miracle-dz/UniFAR-FTUs huggingface dataset:
Hepatitis B Viral RNA Directly Mediates Down-regulation of the Tumor Suppressor MicroRNA miR-15a/miR-16-1 in Hepatocytes*

Background: Hepatitis B virus (HBV) infection has been linked to the development of hepatocellular carcinoma (HCC) in humans. Results: Specific microRNAs inhibit HBV replication, and HBV infection also reprograms microRNA expression. Conclusion: The viral HBx RNA directly mediates the down-regulation of the tumor suppressor microRNA miR-15a/miR-16-1. Significance: The functional interplay between HBV infection and microRNA may contribute to HCC development. Hepatitis B virus (HBV) is a key risk factor for the development of hepatocellular carcinoma (HCC). Recent work suggests a functional link between HCC and microRNA expression, but the mechanism underlying the functional interaction between microRNA and HBV infection has remained largely elusive. Here we present evidence that the microRNA machinery serves as a defense system against HBV infection, which, in turn, reprograms the expression of specific microRNAs. We demonstrate a critical role of miR-15a/miR-16-1 in this functional interplay between microRNA and HBV infection, but in contrast to various indirect mechanisms mediated by viral proteins, we unexpectedly found that the HBx transcript directly triggers the down-regulation of miR-15a/miR-16-1 via the microRNA targeting sequences in the viral RNA. Because miR-15a and miR-16-1 are well known tumor suppressor microRNAs in multiple human cancers, our findings raise the intriguing possibility that viral RNA-mediated down-regulation of specific tumor suppressor microRNAs may contribute to HCC development in HBV-infected cells.
Randomized multicenter phase III trial comparing two neoadjuvant chemoradiotherapy (CT-RT) regimens (RT45-Cap versus RT50-Capox) in patients (pts) with locally advanced rectal cancer (LARC): Results of the ACCORD 12/0405 PRODIGE 2.

LBA4007 The full, final text of this abstract will be available in Part II of the 2009 ASCO Annual Meeting Proceedings, distributed onsite at the Meeting on May 30, 2009, and as a supplement to the June 20, 2009, issue of the Journal of Clinical Oncology. No significant financial relationships to disclose.
Diagnosis and treatment of dementia: 6. Management of severe Alzheimer disease

Background: The management of severe Alzheimer disease often presents difficult choices for clinicians and families. The disease is characterized by a need for full-time care and assistance with basic activities of daily living. We outline an evidence-based approach for these choices based on recommendations from the Third Canadian Consensus Conference on the Diagnosis and Treatment of Dementia. Methods: We developed evidence-based guidelines using systematic literature searches, with specific criteria for the selection and quality assessment of articles, and a clear and transparent decision-making process. We selected articles published from January 1996 to December 2005 that dealt with the management of severe Alzheimer disease. Subsequent to the conference, we searched for additional articles published from January 2006 to March 2008 using the same search terms. We graded the strength of the evidence using the criteria of the Canadian Task Force on Preventive Health Care. Results: We identified 940 articles, of which 838 were selected for further study. Thirty-four articles were judged to be of at least good or fair quality and were used to generate 17 recommendations. Assessment of severe Alzheimer disease should include the measurement of cognitive function and the assessment of behaviour, function, medical status, nutrition, safety and caregiver status. Management could include treatment with a cholinesterase inhibitor or memantine, or both. Treatment of neuropsychiatric symptoms begins with nonpharmacologic approaches to addressing behavioural problems. Severe agitation, aggression and psychosis, which are potentially dangerous to the patient, the caregiver and others in the environment, can be treated with atypical antipsychotics, with consideration of their increased risk of cerebrovascular events and death. All pharmacologic approaches require careful monitoring and periodic reassessment to determine whether continued treatment is necessary. Caregiver support and use of community resources are essential. Interpretation: Severe Alzheimer disease requires frequent monitoring by health professionals. Simple nonpharmacologic approaches may address problems with mood and agitation. Antipsychotic drug therapy is occasionally necessary despite the inherent risks. Therapy with a cholinesterase inhibitor and memantine may be useful for selected patients.
Managing dentin hypersensitivity.

BACKGROUND The objective of this review is to inform practitioners about dentin hypersensitivity (DH) and its management. This clinical information is described in the context of the underlying biology. TYPES OF STUDIES REVIEWED The authors used MEDLINE to find relevant English-language literature published in the period 1999 to 2005. They used combinations of the search terms "dentin*," "tooth," "teeth," "hypersensit*," "desensiti*" and "desensitiz*. " They read abstracts and then full articles to identify studies describing etiology, prevalence, clinical features, controlled clinical trials of treatments and relevant laboratory research on mechanisms of action. RESULTS The prevalence of DH varies widely, depending on the mode of investigation. Potassium-containing toothpastes are the most widely used at-home treatments. Most in-office treatments employ some form of "barrier," either a topical solution or gel or an adhesive restorative material. The reported efficacy of these treatments varies, with some having no better efficacy than the control treatments. Possible reasons for this variability are discussed. A flowchart summarizes the various treatment strategies. CLINICAL IMPLICATIONS DH is diagnosed after elimination of other possible causes of the pain. Desensitizing treatment should be delivered systematically, beginning with prevention and at-home treatments. The latter may be supplemented with in-office modalities.
Dietary vitamin D affects cell-mediated hypersensitivity but not resistance to experimental pulmonary tuberculosis in guinea pigs

Outbred, Hartley strain guinea pigs were fed purified diets varying only in their levels of vitamin D. The amounts of vitamin D in the diets were adjusted to represent 0, 25, 50, 100, or 200% of the recommended level (1,180 IU/kg of body weight) for guinea pigs. In some experiments, half of the animals in each diet group were vaccinated with Mycobacterium bovis BCG vaccine at the time the diets were introduced. Six weeks later, all guinea pigs were infected by the respiratory route with a low dose of virulent M. tuberculosis H37Rv. Vitamin D-deficient animals exhibited marked reductions in levels of the major vitamin D metabolite, 25-hydroxyvitamin D3, in plasma. Altered vitamin D intake was accompanied by changes in antigen (purified protein derivative)-induced, cell-mediated immune responses both in vivo (tuberculin hypersensitivity) and in vitro (lymphoproliferation). Dermal tuberculin reactivity developed more slowly in vitamin D-deficient guinea pigs but eventually achieved normal levels. The proliferation of splenocytes cultured with purified protein derivative was suppressed by both deficiency and excess of dietary vitamin D. Vitamin D status did not affect the abilities of naive guinea pigs to control primary, pulmonary tuberculosis, nor did it influence the protective efficacy of BCG vaccination. We conclude that changes in dietary vitamin D are associated with alterations in some cellular immune functions but may not be an important determinant of disease outcome in pulmonary tuberculosis, as has been suggested previously.
Association Between Knee Osteoarthritis and Functional Changes in Ankle Joint and Achilles Tendon

Abstract Increasing evidence has shown that biomechanical forces often drive the progression of knee osteoarthritis (OA). Attention should be given to the changes in adjacent joints and their relation to knee OA. The purpose of the present study was to examine the changes in Achilles tendon thickness of individuals with knee OA and to evaluate the correlation between Achilles tendon thickness and knee OA severity in a case‐control prospective observational study. A total of 93 participants with no previous ankle injuries were recruited. Of the 93 participants, 63 had knee OA of the medial compartment and 30 served as controls. The subjects underwent a clinical examination that included measurements of weight, height, Achilles tendon thickness, and 1‐leg heel rise. The subjects also underwent a computerized gait test and completed the Hebrew version of the Western Ontario and McMaster Osteoarthritis Index and 36‐item short‐form (SF‐36) health survey. Significant difference was found in Achilles tendon thickness between the subjects with knee OA and the healthy controls (17.1 ± 3.4 versus 15.1 ± 3.1; p = .009). Significant differences were also found between the 2 groups in the 1‐leg heel rise test, Western Ontario and McMaster Osteoarthritis Index scores, SF‐36 scores, and all gait measures. Significant correlations were found between the Achilles tendon thickness and the following measures: weight (r = 0.46), body mass index (r = 0.55), Kellgren and Lawrence OA severity grade (r = 0.25), 1‐leg heel rises (r = −0.50), and SF‐36 score (r = −0.25). Subjects with knee OA presented with a thicker Achilles tendon compared with the healthy controls. Furthermore, a significant correlation between Achilles tendon thickness and knee OA severity was found. A comprehensive assessment of the Achilles tendon and ankle joint should be a part of the knee OA evaluation process. &NA; Level of Clinical Evidence: 3
FSH suppression does not affect bone turnover in eugonadal men.

CONTEXT In vitro and animal studies have reported conflicting results regarding an independent role for FSH in the regulation of bone turnover. OBJECTIVE Our objective was to test the hypothesis that suppressing serum FSH while holding serum gonadal steroid levels stable in the eugonadal range will affect biochemical markers of bone metabolism in healthy men. PARTICIPANTS, DESIGN, AND SETTING Eugonadal men aged 20 to 50 years participated in this randomized controlled trial at a tertiary care academic teaching hospital. INTERVENTIONS Participants received monthly GnRH analog injections to suppress FSH secretion plus daily topical testosterone gel in prespecified doses (intervention group). Controls received matching placebos (control group). Subjects in the intervention group were individually matched with subjects in the control group to ensure that the mean testosterone and estradiol levels (measured every 4 weeks during the 16-week study period) in the 2 groups were similar. MAIN OUTCOME MEASURES Biochemical markers of bone resorption (serum N-terminal telopeptide and C-terminal telopeptide), bone formation (serum osteocalcin), and FSH were measured at baseline and after 16 weeks of treatment. RESULTS Serum FSH declined by 2% in the control group and by 60% in the intervention group (P < .0001 for the between-group difference). Despite the substantial suppression of serum FSH in the intervention group, serum N-terminal telopeptide, C-terminal telopeptide, and osteocalcin did not change in the intervention group, nor were any between-group differences observed. CONCLUSION When gonadal steroid levels are held constant, short-to midterm suppression of FSH does not affect bone turnover in men. FSH does not appear to be a significant regulator of bone metabolism in eugonadal men.
Kinetic study of free and immobilized protease from Aspergillus sp

In the present investigation partially purified alkaline protease from Aspergillus sp. As#6 and As#7 strains were entrapped in calcium alginate beads and characterized using casein as a substrate. Temperature and pH maxima of protease from As#6 strain showed no changes before and after immobilization and remained stable at 45C and pH 9, respectively. However km value was slightly shifted from 4.5mg/ml to 5 mg/ml. Proteases from As#7 strain showed shifting in pH optima to a more alkaline range (10.0) as compared with free enzyme (9.0). Optimum temperature for protease from As#7 strain showed changes after immobilization and shifted from 65C to 85C. However there was no significant effect on Km value but Vmax of immobilized protease from As#7 strain was also shifted from 200U/ml to 370U/ml. Immobilized protease from As#6 strain was reused for 3 cycles with 22% loss in its activity whereas immobilize protease from As#7 strain was reused for 3 cycles with 17% loss in its activity. Protease from As#7 strain has a higher affinity for the substrate and higher proteolysis activity than protease from As#6 strain. The present work concludes that Aspergillus As#7 strain may be a good source of industrial protease.
Cloning and characterisation of genes (pkc1 and pkcA) encoding protein kinase C homologues from Trichoderma reesei and Aspergillus niger.

Oligonucleotides, designed on the basis of conserved flanking amino acid sequence segments within the catalytic domain of eukaryotic protein kinase C (PKC) proteins, were used as primers for polymerase chain reactions to amplify a 427-bp chromosomal DNA fragment from the filamentous fungus Trichoderma reesei. This fragment was then used to isolate genes encoding PKC homologues of T. reesei and Aspergillus niger (pkc1 and pkcA, respectively). The genes contain six (T. reesei) and eight (A. niger) introns, which exhibit notable conservation in position with those found in the corresponding Schizosaccharomyces pombe pkc1+ and Drosophila melanogaster dPKC53Ebr genes. A single 4.2-kb transcript was detected in Northern analyses. The deduced PKC1 (T.reesei, 126 kDa) and PKCA (A. niger, 122 kDa) amino acid sequences reveal domains homologous to the C1 and C3/C4 domains of PKC-related proteins, but lack typical Ca(2+)-binding (C2) domains. Both contain a large, extended N-terminus, which shares a high degree of similarity with the corresponding regions of Saccharomyces cerevisiae PKC1 and S. pombe pkc1+ and pkc2+ proteins, but which is not present in PKCs of Dictyostelium or higher eukaryotes. This extended region can be divided into three subdomains; the N-terminal one contains a hydrophobic helix-turn-helix motif, whereas the C-terminal one contains potential targets for proteolytic processing. A polyclonal antiserum raised against the pseudosubstrate-binding domain of PKC1 recognizes in T. reesei a 115-120 kDa protein in Western blots. Expression of pkc1 cDNA in insect cells directs the synthesis of a PKC1 protein of similar size. The T. reesei PKC1 protein was partially purified and some of its properties examined: it is stimulated about twofold by phospholipids or phorbol esters but is not stimulated by Ca2+. We conclude that these PKC proteins from filamentous fungi represent the Ca(2+)-insensitive fungal homologues of the nPKC family.
Central venous catheter infusions: A laboratory model shows large differences in drug delivery dynamics related to catheter dead volume *

Objective: Central venous catheters (CVCs) are conduits for drug infusions. Dead volumes of different CVC lumens vary considerably. This study quantitatively evaluated drug delivery dynamics of CVCs in a laboratory model of continuous drug infusion. Design: CVCs studied included a triple‐lumen catheter (16‐gauge and 18‐gauge lumens), the proximal infusion port of a pulmonary artery catheter, and a 9‐Fr introducer sheath, with and without a pulmonary artery catheter in the lumen. One syringe pump infused a carrier. A second pump infused the model drug methylene blue (3 mL/hr), joining the carrier immediately upstream of the CVC. Samples were collected every minute for quantitative analysis. Setting: Laboratory model. Subjects: None. Interventions: At low fixed flow rates, experiments characterized drug delivery kinetics of different CVCs. Data collection then assessed effects of increased carrier flow. Measurement and Main Results: The time to steady‐state delivery after initiation of methylene blue infusion differed between CVCs. At a carrier flow of 10 mL/hr, the fastest achievement of steady‐state delivery was with the 18‐gauge lumen of a triple‐lumen catheter. The 9‐Fr introducer had the slowest time to achieve steady‐state delivery. Other CVCs had intermediate kinetics. Reducing drug delivery from steady state to zero after cessation of methylene blue infusion was fastest with the 18‐gauge lumen and slowest with the 9‐Fr introducer. Increasing carrier flow rates from 10 to 60 mL/hr hastened the time to target for initiation and cessation of methylene blue delivery. Conclusions: Experiments demonstrate large differences between CVCs in the dynamics for delivery of model drug methylene blue. Achieving targeted steady‐state delivery, and termination of a planned continuous drug infusion, may be far slower than typically appreciated. Delivery kinetics depend on the dead volume and the rate of carrier flow. Safe and effective management of continuous drug infusions depends on understanding the dynamics of the delivery system.
The (QxW)3 domain: A flexible lectin scaffold

Lectins form a class of proteins that have evolved a specialized carbohydrate‐binding function. Based on amino acid sequence analysis, several lectin families have been described and a lectin domain, the (QxW)3 domain, was discussed recently based on 11 family members. In this paper, the (QxW)3 domain family is extended to 45 sequences, several of which have very low sequence identity with the previously known members of the family. A hidden Markov model was used to identify the most divergent members of the family. The expanded set of sequences gives us a more complete appreciation of the conserved features, and the lack thereof, in this lectin family. This, in turn, provides new insights in the structural and functional properties of the individual family members.
The responses to somatic stimuli of deep spinothalamic tract cells in the lumbar spinal cord of the cat

1. The responses to natural somatic stimuli of thirty‐seven antidromically identified spinothalamic tract (s.t.t.) cells in Rexed's laminae VII and VIII of the lumbar spinal cord of the cat have been studied. A further twenty‐eight s.t. t. cells were identified antidromically.
Evaluation of advanced airway management in absolutely inexperienced hands: a randomized manikin trial

Aims Endotracheal intubation (ETI) and basic ventilation techniques (i.e. mouth-to-mouth/nose, bag-valve-mask ventilation) require skills and training. As an alternative, supraglottic airway devices (SAD) are efficient and technically easy to insert. We therefore evaluated the time to ventilation, success rate, and skill retention for various airway management approaches by medical laypersons using a manikin model. Methods Fifty medical laypersons with no previous experience whatsoever in airway management or resuscitation were enrolled. All participants received a 1-h-long theoretical lecture and a practical demonstration of mouth-to-mouth ventilation, ETI, and six SAD. Afterwards, the laypersons performed mouth-to-mouth ventilation and used each of the seven airway-management systems on an advanced patient simulator (SimMan) in a random sequence. All participants were re-evaluated 3 months later without any further practical or theoretical demonstration. Results The success rates for ETI were 74% during the first evaluation and 64% during the second, whereas the success rate for all six SAD was 100% during all application attempts. The success rate for mouth-to-mouth ventilation was 86% initially and 84% 3 months later. The time to adequate mouth-to-mouth ventilation was 15±13 s initially and 16±7 s subsequently. ETI required 53±21 s during the initial evaluation and 44±16 s 3 months later. Conclusion A variety of SAD all proved to reliably secure airways quickly, even in the hands of complete novices. The SAD were much more effective than ETI, which often failed, and were even superior to mouth-to-mouth ventilation. SAD may thus be an appropriate first-line approach to field ventilation.
Higher Cardiorespiratory Fitness in Older Trained Women is Due to Preserved Stroke Volume.

UNLABELLED Previous literature has shown that sedentary older women rely on peripheral adaptations to improve cardiorespiratory fitness with endurance training i.e. they show minimal increases in central parameters (cardiac output, Q) in response to endurance training. The purpose of this study therefore was to determine whether endurance trained older women were able to preserve maximal exercise Q and were characterized by a high stroke volume (SV) when compared to physically inactive older women. Trained (n = 7) and untrained (n = 1 0) women attended two maximal and one submaximal laboratory session. Breath-by-breath analysis was conducted using mass spectrometry and Q was assessed using acetylene open circuit inert gas wash-in. Multivariate analysis of variance and paired samples t-tests were used to determine between and within group differences. Trained women had a significantly higher VO2max (37.5 vs. 24.1 ml(-1)·kg·min(-1)) compared to untrained women. There were no differences for peripheral oxygen extraction (VO2/Q) at either submaximal or maximal work rates; however trained women had a significantly higher SV at maximal (119.3 vs. 94.6 ml) exercise compared to untrained women. In both trained and untrained women, SV did not rise significantly between submaximal and maximal exercise. CONCLUSION Highly fit, endurance trained older women are able to preserve central parameters of VO2max. Peripheral oxygen extraction is similar between older trained and untrained women.
Loss Given Default Estimation: A Two-Stage Model with Classification Tree-Based Boosting and Support Vector Logistic Regression

The Basel Accords allow banks to estimate credit risk. Accordingly, more attention has been dedicated recently to the analysis of loss given default (LGD) and the development of an LGD estimation model. In this study, using a data set composed of five Japanese regional banks, we propose an LGD estimation model using a two-stage model, classification tree-based boosting and support vector regression (SVR). We compare the proposed model’s predictive performance with existing models by performing cross-validation and out-of-time validation. As a result, we find that incorporating nonlinearity into the LGD estimation model by classification and SVR improves its predictive performance. Further, we confirm that the boosting method improves the model’s predictive performance.
Two-sided altruism as a motive for intergenerational transfer

Abstract This paper reconsiders the role of altruism as a motive for an intergenerational transfer and characterizes the relationship between intergenerational transfers and altruism. The main finding is that transfers to children do not disappear even if altruism from parents to children weakens. The paper also shows that as altruism from children to parents becomes stronger, a transfer to children initially decreases and then increases once the degree of altruism is beyond a certain level; in other words, transfers may increase even if altruism from the transferee to the transferor becomes stronger. These findings sharply contrast with the common assumption in the existing literature that an intergenerational transfer is motivated by altruism from the transferor to the transferee.