Miracle-dz/UniFAR-FTUs huggingface dataset:
nhanced oral bioavailability of docetaxel in rats by four consecutive days of retreatment with curcumin

As with many other anti-cancer agents, docetaxel is a substrate for ATP-binding cassette transporters such as P-glycoprotein and its metabolism is mainly catalysed by CYP3A. In order to improve the oral bioavailability of docetaxel, a component of turmeric, curcumin, which can down-regulate the intestinal P-glycoprotein and CYP3A protein levels, was used for the pre-treatment of rats before the oral administration of docetaxel. Curcumin (100 mg/kg) did not significantly modify the pharmacokinetics of docetaxel when given orally 30 min before the administration of docetaxel. However, the Cmax
A Scalable Weighted Max-SAT Implementation of Propositional Etcetera Abduction

Recent advances in technology for abductive reasoning, or inference to the best explanation, encourage the application of abduction to real-life commonsense reasoning problems. This paper describes Etcetera Abduction, a new implementation of logical abduction that is both grounded in probability theory and optimized using contemporary linear programming solvers. We present a Weighted Max-SAT formulation of Etcetera Abduction, which allows us to exploit highly advanced technologies developed in the field of SAT and Operations Research. Our experiments demonstrate the scalability of our proposal on a large-scale synthetic benchmark that contains up to ten thousand axioms, using one of the state-of-the-art mathematical optimizers developed in these fields. This is the first work to evaluate a SAT-based approach to abductive reasoning at this scale. The inference engine we developed has been made publicly available.
Long-term renal outcomes in patients with primary aldosteronism.

CONTEXT Experimental animal studies indicate that exposure to increased aldosterone levels might result in renal damage, but the clinical evidence supporting this role of aldosterone is preliminary. OBJECTIVE To determine the long-term outcome of renal function in patients with primary aldosteronism after surgical or medical treatment. DESIGN, SETTING, AND PARTICIPANTS Prospective study conducted at an Italian university medical center among a consecutive sample of 50 patients who were diagnosed as having primary aldosteronism between January 1994 and December 2001 and who were followed up for a mean of 6.4 years after treatment with adrenalectomy or spironolactone. Patients with primary aldosteronism were compared with 100 patients with essential hypertension, matched for severity and duration of hypertension. All patients were treated with antihypertensive drugs to reach a target blood pressure of less than 140/90 mm Hg. MAIN OUTCOME MEASURES Primary outcome measures were rates of change of glomerular filtration rate and albuminuria during follow-up. Detection of new-onset microalbuminuria and restoration of normal albumin excretion during follow-up were considered as secondary outcomes. RESULTS At baseline, glomerular filtration rate and albuminuria were higher in patients with primary aldosteronism than those with essential hypertension. The mean blood pressure during the study was 136/81 mm Hg in the primary aldosteronism group and 137/81 mm Hg in the essential hypertension group. Glomerular filtration rate and albuminuria declined during the initial 6-month period in both groups, with a change that was significantly greater (P<.001 for both variables) in patients with primary aldosteronism. Subsequent rate of decline of glomerular filtration was comparable in the 2 groups, whereas albuminuria did not progress in the remainder of the follow-up. Restoration of normal albumin excretion from microalbuminuria was significantly more frequent in primary aldosteronism than in essential hypertension (P = .02). CONCLUSION In the majority of patients in this study, primary aldosteronism was characterized by partially reversible renal dysfunction in which elevated albuminuria is a marker of a dynamic rather than structural renal defect.
General Saddlepoint Approximation for Testing Separate Location-Scale Families of Hypotheses

For testing separate families of hypotheses, the likelihood ratio test does not have the usual asymptotic properties. This paper considers the asymptotic distribution of the ratio of maximized likelihoods (RML) statistic in the special case of testing separate scale or location-scale families of distributions. We derive saddlepoint approximations to the density and tail probabilities of the log of the RML statistic. These approximations are based on the expansion of the log of the RML statistic up to the second order, which is shown not to depend on the location and scale parameters. The resulting approximations are applied in several cases, including normal versus Laplace, normal versus Cauchy, and Weibull versus log-normal. Our results show that the saddlepoint approximations are satisfactory, even for fairly small sample sizes, and are more accurate than normal approximations and Edgeworth approximations, especially for tail probabilities that are the values of main interest in hypothesis testing problems.
Leaky Scanning and Scanning-independent Ribosome Migration on the Tricistronic S1 mRNA of Avian Reovirus*

The S1 genome segments of avian and Nelson Bay reovirus encode tricistronic mRNAs containing three sequential partially overlapping open reading frames (ORFs). The translation start site of the 3′-proximal ORF encoding the σC protein lies downstream of two ORFs encoding the unrelated p10 and p17 proteins and more than 600 nucleotides distal from the 5′-end of the mRNA. It is unclear how translation of this remarkable tricistronic mRNA is regulated. We now show that the p10 and p17 ORFs are coordinately expressed by leaky scanning. Translation initiation events at these 5′-proximal ORFs, however, have little to no effect on translation of the 3′-proximal σC ORF. Northern blotting, insertion of upstream stop codons or optimized translation start sites, 5′-truncation analysis, and poliovirus 2A protease-mediated cleavage of eIF4G indicated σC translation derives from a full-length tricistronic mRNA using a mechanism that is eIF4G-dependent but leaky scanning- and translation reinitiation-independent. Further analysis of artificial bicistronic mRNAs failed to provide any evidence that σC translation derives from an internal ribosome entry site. Additional features of the S1 mRNA and the mechanism of σC translation also differ from current models of ribosomal shunting. Translation of the tricistronic reovirus S1 mRNA, therefore, is dependent both on leaky scanning and on a novel scanning-independent mechanism that allows translation initiation complexes to efficiently bypass two functional upstream ORFs.
Meta-Analysis and Decision Analysis Bridge Research and Practice

Research synthesis methods provide meaningful quantitative data through systematic review of the research literature and translation of these findings into practice implications. Meta-analysis has been the gold standard for translation of research findings into practice. Decision analysis has emerged as an alternative to and extension of meta-analysis. Examples, contrasting the application of meta-analysis and decision analysis, are presented and discussed in relation to its relevance in providing clinical direction. The methods are points along the continuum of translating research findings into practice. Meta-analytic studies provide an essential foundation for estimating and assigning the probabilities used in decision analysis, whereas the outcomes of decision analysis provide data for estimating the cost effectiveness of different interventions or treatment options. Decision analysis can assist in bridging the research-practice gap. Nurse researchers are urged to collaborate with other disciplines that have used these methods to refine translation and use of research findings in practice.
C. H. McCloy Lecture: Reflections on Socialization Into Physical Education: An Intergenerational Perspective

Charles H. McCloy was an icon in our profession. He was not only a leading researcher in the area of anthropometrics and tests and measurements, but he was a leading advocate for physical education (PE) in our country. McCloy's advocacy ties nicely into the authors' belief that the socialization process has a profound impact on the state of PE in our country. Grounded in nearly 40 years of research related to teacher socialization, the purpose of this manuscript is to provide an overview of the socialization of PE teachers across the phases of acculturation, professional socialization, and organizational socialization. Research pertaining to each of the phases is reviewed and then connected to an intergenerational comparison of the authors' autobiographical experiences in PE. The article concludes with propositions and implications about the socialization process and recommendations for future research.
Effects of a Malpractice Crisis on Specialist Supply and Patient Access to Care

Objective:To investigate specialist physicians' practice decisions in response to liability concerns and their perceptions of the impact of the malpractice environment on patient access to care. Summary Background Data:A perennial concern during “malpractice crises” is that liability costs will drive physicians in high-risk specialties out of practice, creating specialist shortages and access-to-care problems. Methods:Mail survey of 824 Pennsylvania physicians in general surgery, neurosurgery, orthopedic surgery, obstetrics/gynecology, emergency medicine, and radiology eliciting information on practice decisions made in response to rising liability costs. Results:Strong majorities of specialists reported increases over the last 3 years in patients' driving distances (58%) and waiting times (83%) for specialist care or surgery, waiting times for emergency department care (82%), and the number of patients forced to switch physicians (89%). Professional liability costs and managed care were both considered important contributing factors. Small proportions of specialists reported that they would definitely retire (7%) or relocate their practice out of state (4%) within the next 2 years; another third (32% and 29%, respectively) said they would likely do so. Forty-two percent of specialists have reduced or eliminated high-risk aspects of their practice, and 50% are likely to do so over the next 2 years. Conclusions:Our data suggest that claims of a “physician exodus” from Pennsylvania due to rising liability costs are overstated, but the malpractice situation is having demonstrable effects on the supply of specialist physicians in affected areas and their scope of practice, which likely impinges upon patients' access to care.
Knowledge sharing in context: the influence of organizational commitment, communication climate and CMC use on knowledge sharing

Determining which factors promote or impede the sharing of knowledge within groups and organizations constitutes an important area of research. This paper focuses on three such influences: “organizational commitment,” “organizational communication,” and the use of a specific instrument of communication – computer‐mediated communication (CMC). Two processes of knowledge sharing are distinguished: donating and collecting. A number of hypotheses are presented concerning the influence of commitment, climate and CMC on these processes. These hypotheses were tested in six case studies. The results suggest that commitment to the organization positively influences knowledge donating, and is in turn positively influenced by CMC use. Communication climate is found to be a key variable: a constructive communication climate was found to positively influence knowledge donating, knowledge collecting and affective commitment. Finally, a relationship was found that was not hypothesized: knowledge collecting influences knowledge donating in a positive sense – the more knowledge a person collects, the more he or she is willing to also donate knowledge to others. Based on these results, a number of theoretical and practical implications are discussed, and suggestions for further research are presented.
Persistent neuropathy after treatment with cisplatin and oxaliplatin

Background. The aims of the current explorative study were to assess persistent neuropathy in 45 patients up to 6 years after treatment with cisplatin or oxaliplatin and to determine the most adequate method to evaluate neuropathy. Furthermore, the effect of possible determinants on persistent neuropathy was investigated. Material andmethods. The assessment of neuropathy was performed using a questionnaire, by neurological tests, and by vibration threshold (VT) measurements. Because VT determination gives the most objective information, VT measurements were used for further analyses. Results and discussion. The analyses revealed that neuropathy of the hands was related to follow-up time, with an observed recovery half-life of 6.8 (± 3.1) years. No significant reversibility of neuropathy of the feet within the observation period could be demonstrated. For cisplatin, the severity of neuropathy was related to the cumulative dose and sodium thiosulfate use. Oxaliplatin induced neuropathy did not appear to be related to the dose within the studied dose range. No relationship with platinum levels, renal function, glutathione transferase genotypes, diabetes mellitus, alcohol use, or co-medication could be demonstrated. This study was performed as an explorative study and the issues discussed need to be investigated further.
In situ localization of S‐phase‐specific histone (H3) mRNA in Bowen's disease

PCNA and Ki‐67 immunohistochemistry has been used to assess cell proliferation in place of tritiated thymidine or BrdU labeling of S‐phase cells. Recently, it has been possible to reliably demonstrate histone H3 mRNA by in situ hybridization in formalin‐fixed and paraffin‐embedded tissue sections. We have compared this new proliferation marker with Ki‐67 and PCNA with regard to distribution of positive cells and labeling indices (LI%) for 22 cases of Bowen's disease.
Hepatic artery thrombosis in pediatric liver transplantation: Graft salvage after thrombectomy

Abstract: Hepatic artery thrombosis (HAT) is a devastating complication that may occur after orthotopic liver transplantation (OLT). A higher incidence has been reported in children. Salvage of the graft by thrombectomy has been suggested as an alternative to re‐transplantation. In this study we report the outcome of three children who underwent thrombectomy for HAT. Between January 1992 and June 1998, 14 children (< 17 yrs of age) underwent liver transplantation. Three developed HAT (one a whole‐liver graft recipient, age 17; two living‐related graft recipients, ages 4 and 4.5 yr). In the first patient, thrombosis of the hepatic artery was associated with scattered areas of parenchymal necrosis on computed tomography. In the two living‐related patients, HAT was found incidentally during re‐exploration for bleeding (day 2 and day 10). Thrombectomy was performed in all three patients. At 18–24 months after thrombectomy, all three children had normal graft function. In the first patient, complete regeneration of the liver has been documented by computed tomography and a late asymptomatic recurrent thrombosis is suggested by absence of arterial flow on Doppler examination. The hepatic artery is patent in the two living‐related recipients. One of these living‐related recipients developed ischemic bile duct stricture and underwent successful percutaneous balloon dilatation. We conclude that long‐term normal graft function can be achieved by thrombectomy in pediatric liver recipients with HAT, even in the presence of limited parenchymal damage.
Effective use of a strategy using assigned red cell units to limit donor exposure for neonatal patients

Critically ill neonatal infants receive frequent small‐volume red cell (RBC) transfusions for replacement of blood drawn for laboratory analysis or for treatment of symptomatic anemia secondary to underlying medical conditions and/or a relative bleeding diathesis. Retrospective review of transfusion practice in a hospital revealed that the donor exposure‐to‐transfusion ratio was 1:1.3. In an effort to limit donor exposure and decrease the risk of transfusion‐transmitted disease, a sterile connection device was used for multiple small‐aliquot preparations. Three neonatal infants were given part of the same RBC unit, and the assigned RBC unit was used only until it reached 14 days of age. These criteria resulted in 49‐percent reduction in donor exposure for neonatal infants weighting less than 1500 g and 27‐percent reduction for those weighing more than 1500 g. The donor exposure‐to‐ transfusion ratio decreased to 1:2.5. RBC waste from syringe aliquot preparation and residual volume at Day 15 were a mean of 32 percent of the total unit volume. Of 722 transfusion occurrences, there were no reported adverse effects due to elevated potassium subsequent to transfusion of 14‐day‐old RBCs. This limited‐donor‐exposure strategy effectively meets the needs of a transfusion service and will reduce the donor exposures of neonatal infants in similar institutions.
Early inflammatory response of knee ligaments to prolotherapy in a rat model

Prolotherapy is an alternative injection‐based therapy for chronic musculoskeletal pain. Three different proliferants, D‐glucose (dextrose), phenol‐glucose‐glycerine (P2G), and sodium morrhuate, used in prolotherapy are hypothesized to strengthen and reorganize chronically injured soft tissue and decrease pain through modulation of the inflammatory process. Our hypothesis is that commonly used prolotherapy solutions will induce inflammation (leukocyte and macrophage infiltration) in medial collateral ligaments (MCLs) compared to needlestick, saline injection, and no‐injection controls. MCLs of 84 Sprague‐ Dawley rats were injected one time at both the tibial and femoral insertions. Immunohistochemistry (IHC) was used to determine the inflammatory response at three locations (tibial and femoral insertions and midsubstance) 6, 24, and 72 h after dextrose injection compared to saline‐ and no‐injection controls and collagenase (positive control) (n = 4). qPCR was used to analyze gene expression 24 h postinjection (n = 4). Sodium morrhuate, P2G, and needlestick control were also investigated after 24 h (n = 4). In general, inflammation (CD43+, ED1+, and ED2+ cells) increased after prolotherapy injection compared to no‐injection control but did not increase consistently compared to saline and needlestick control injections. This response varied by both location and proliferant. Inflammation was observed at 6 and 24 h postinjection but was resolved by 72 h compared to no‐injection controls (p < 0.05). CD43+ leukocytes and ED2+ macrophages increased compared to needlestick and saline‐injection control, respectively, 24 h postinjection (p < 0.05). Prolotherapy injections created an inflammatory response, but this response was variable and overall, not uniformly different from that caused by saline injections or needlestick procedures. © 2008 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 26:816–823, 2008
Sodium alginate/cellulose nanocrystal fibers with enhanced mechanical strength prepared by wet spinning

Sodium alginate/cellulose nanocrystal fibers were prepared using a wet spinning method to enhance the mechanical strength of sodium alginate fibers. Cellulose nanocrystals were prepared by sulfuric acid hydrolysis method. The particle diameter size was measured, and the morphology of cellulose nanocrystals was characterized by transmission electron microscopy and scanning electron microscopy. The structure and mechanical properties of sodium alginate/cellulose nanocrystal fibers were characterized by scanning electron microscopy, transmission electron microscopy, X-ray diffraction, and mechanical strength testing. The incorporation of cellulose nanocrystals significantly improved the strength of alginate fibers because of the uniform distribution of cellulose nanocrystals in the alginate matrix. The tensile strength and elongation at break of the alginate fibers increased from 1.54 to 2.05 cN/dtex and from 8.29% to 15.05% with increasing cellulose nanocrystals content from 0 to 2 wt%, respectively.
Subthreshold Ca2+-dependent modulation of vesicle release dynamics and docking site occupancy at single central synapses

Dans plusieurs neurones du SNC l'activite somato-dendritique infraliminaire peut se propager passivement dans l'axone et augmenter transitoirement la transmission synaptique spontanee et evoquee par le potentiel d'action de maniere dependante du Ca2+. Les mecanismes sousjacents a ce type de plasticite synaptique, appelee facilitation "analogique" ou "analogo-digitale", restent largement inconnus pour la plupart des synapses centrales, principalement en raison de la difficulte a realiser des enregistrements directs des petits boutons presynaptiques. Ici, nous utilisons de la photolyse de Ca2+ et de l'imagerie aux niveau des terminaisons presynaptiques individuelles des interneurones de la couche moleculaire du cervelet (ICM), combinees a des enregistrements electrophysiologiques avec la technique du patch. Nous decrivons un nouveau mecanisme de facilitation analogo-digitale qui est dependant du Ca2+ infraliminaire et dans lequel la fraction et la cinetique du pool de vesicules dites “pretes a etre liberees” (readily releasable pool ou RRP en anglais), est modulee par des modifications de la probabilite d'occupation des sites d'ancrage dans des contacts synaptiques individuels. Nos resultats ajoutent une nouvelle dimension a la comprehension de la maniere dont l'activite infraliminaire module le flux d'information dans les circuits neuronaux
Strongyloides stercoralis in the Immunocompromised Population

SUMMARY Strongyloides stercoralis is an intestinal nematode of humans that infects tens of millions of people worldwide. S. stercoralis is unique among intestinal nematodes in its ability to complete its life cycle within the host through an asexual autoinfective cycle, allowing the infection to persist in the host indefinitely. Under some conditions associated with immunocompromise, this autoinfective cycle can become amplified into a potentially fatal hyperinfection syndrome, characterized by increased numbers of infective filariform larvae in stool and sputum and clinical manifestations of the increased parasite burden and migration, such as gastrointestinal bleeding and respiratory distress. S. stercoralis hyperinfection is often accompanied by sepsis or meningitis with enteric organisms. Glucocorticoid treatment and human T-lymphotropic virus type 1 infection are the two conditions most specifically associated with triggering hyperinfection, but cases have been reported in association with hematologic malignancy, malnutrition, and AIDS. Anthelmintic agents such as ivermectin have been used successfully in treating the hyperinfection syndrome as well as for primary and secondary prevention of hyperinfection in patients whose exposure history and underlying condition put them at increased risk.