Miracle-dz/UniFAR-FTUs huggingface dataset:
Increased risk for nonmelanoma skin cancers in patients who receive thiopurines for inflammatory bowel disease.

BACKGROUND & AIMS Patients with inflammatory bowel disease (IBD) who have been exposed to thiopurines might have an increased risk of skin cancer. We assessed this risk among patients in France. METHODS We performed a prospective observational cohort study of 19,486 patients with IBD, enrolled from May 2004 to June 2005, who were followed up until December 31, 2007. The incidence of nonmelanoma skin cancer (NMSC) in the general population, used for reference, was determined from the French Network of Cancer Registries. RESULTS Before the age of 50 years, the crude incidence rates of NMSC among patients currently receiving or who previously received thiopurines were 0.66/1000 and 0.38/1000 patient-years, respectively; these values were 2.59/1000 and 1.96/1000 patient-years for the age group of 50 to 65 years and 4.04/1000 and 5.70/1000 patient-years for patients older than 65 years. Among patients who had never received thiopurines, the incidence of NMSC was zero before the age of 50 years, 0.60/1000 for the ages of 50 to 65 years, and 0.84/1000 for those older than 65 years. A multivariate Cox regression model stratified by propensity score quintiles showed that ongoing thiopurine treatment (hazard ratio [HR], 5.9; 95% confidence interval [CI], 2.1-16.4; P = .0006) and past thiopurine exposure (HR, 3.9; 95% CI, 1.3-12.1; P = .02) were risk factors for NMSC. They also identified age per 1-year increase as a risk factor for NMSC (HR, 1.08; 95% CI, 1.05-1.11; P < .0001). CONCLUSIONS Ongoing and past exposure to thiopurines significantly increases the risk of NMSC in patients with IBD, even before the age of 50 years. These patients should be protected against UV radiation and receive lifelong dermatologic screening.
Enhanced active metabolite generation and platelet inhibition with prasugrel compared to clopidogrel regardless of genotype in thienopyridine metabolic pathways

Summary Clopidogrel response varies according to the presence of genetic polymorphisms. The CYP2C19*2 allele has been associated with impaired response; conflicting results have been reported for CYP2C19*17, ABCB1, and PON1 genotypes. We assessed the impact of CYP2C19, PON1, and ABCB1 polymorphisms on clopidogrel and prasugrel pharmacodynamic (PD) and pharmacokinetic (PK) parameters. Aspirin-treated patients (N=194) with coronary artery disease from two independent, prospective, randomised, multi-centre studies comparing clopidogrel (75 mg) and prasugrel (10 mg) were genotyped and classified by predicted CYP2C19 metaboliser phenotype (ultra metabolisers [UM] = *17 carriers; extensive metabolisers [EM] = *1/1 homozygotes; reduced metabolisers [RM] = *2 carriers). ABCB1 T/T and C/T polymorphisms and PON1 A/A, A/G and G/G polymorphisms were also genotyped. PD parameters were assessed using VerifyNow® P2Y12 and vasodilator stimulated phosphoprotein (VASP) expressed as platelet reactivity index (PRI) after 14 days of maintenance dosing. Clopidogrel and prasugrel active metabolite (AM) exposure was calculated in a cohort of 96 patients. For clopidogrel, genetic variants in CYP2C19, but not ABCB1 or PON1, affected PK and PD. For prasugrel, none of the measured genetic variants affected PK or PD. Compared with clopidogrel, platelet inhibition with prasugrel was greater even in the CYP2C19 UM phenotype. Prasugrel generated more AM and achieved greater platelet inhibition than clopidogrel irrespective of CYP2C19, ABCB1, and PON1 polymorphisms. The lack of effect from genetic variants on prasugrel AM generation or antiplatelet activity is consistent with previous studies in healthy volunteers and is consistent with improved efficacy in acute coronary syndrome patients managed with percutaneous coronary intervention.
The adaptiveness of defence strategies against cuckoo parasitism

Host bird species of the Eurasian Cuckoo, Cuculus canorus, often display egg-discrimination behaviour but chick-rejection behaviour has never been reported. In this paper, we analyse a host-cuckoo association in which both population dynamics and evolutionary dynamics are explored in a discrete-time model. We introduce four host types, each with their own defence behaviour, displaying either egg or chick rejection, neither or both, We also introduce fitness functions for each of these host types. Although we can characterize the long term behaviour in many cases by a simple heuristic argument which is in accordance with common views in ecology, there are a number of other phenomena that are not explained within this framework: we describe stable oscillatory behaviour and coexistence of two defensive host types. We analyse the scenarios in which chick rejection may establish itself and give a first explanation as to why this defence trait has never been recorded in nature. We find that chick rejectors generally are at an intrinsic disadvantage with respect to a host type that rejects eggs. Hosts benefit more from rejecting cuckoo eggs than cuckoo chicks, and our model suggests that this is chiefly responsible for the absence of chick rejection. Moreover, even though it seems that chick rejection must be useful as an extra defence, it is shown that hosts with both defence strategies are less likely to establish themselves in competition with egg-rejectors than hosts which reject chicks only. These results provide insight in the extent to which adaptations may be perfected by natural selection.
Gonadal brucellar abscess: Imaging and clinical findings in 3 cases and review of the literature

We report the cases of 3 patients with brucellar gonadal abscess who were examined with gray‐scale and color Doppler sonography. In these 3 cases, sonography revealed a thick‐walled avarian (n = 2) or testicular (n = 1) abscess. Duplex Doppler sonography indicated a low‐resistance type of flow in all 3 patients. The diagnosis of brucellar gonadal abscess is difficult, because it may have a misleading tumor‐like appearance. Awareness of the imaging findings of gonadal abscess in patients with brucellosis and correlation with the results of serologic testing can allow early diagnosis, especially in endemic areas. © 2007 Wiley Periodicals, Inc. J Clin Ultrasound, 2007
Guided medication dosing for inpatients with renal insufficiency.

CONTEXT Usual drug-prescribing practices may not consider the effects of renal insufficiency on the disposition of certain drugs. Decision aids may help optimize prescribing behavior and reduce medical error. OBJECTIVE To determine if a system application for adjusting drug dose and frequency in patients with renal insufficiency, when merged with a computerized order entry system, improves drug prescribing and patient outcomes. DESIGN, SETTING, AND PATIENTS Four consecutive 2-month intervals consisting of control (usual computerized order entry) alternating with intervention (computerized order entry plus decision support system), conducted in September 1997-April 1998 with outcomes assessed among a consecutive sample of 17 828 adults admitted to an urban tertiary care teaching hospital. INTERVENTION Real-time computerized decision support system for prescribing drugs in patients with renal insufficiency. During intervention periods, the adjusted dose list, default dose amount, and default frequency were displayed to the order-entry user and a notation was provided that adjustments had been made based on renal insufficiency. During control periods, these recommended adjustments were not revealed to the order-entry user, and the unadjusted parameters were displayed. MAIN OUTCOME MEASURES Rates of appropriate prescription by dose and frequency, length of stay, hospital and pharmacy costs, and changes in renal function, compared among patients with renal insufficiency who were hospitalized during the intervention vs control periods. RESULTS A total of 7490 patients were found to have some degree of renal insufficiency. In this group, 97 151 orders were written on renally cleared or nephrotoxic medications, of which 14 440 (15%) had at least 1 dosing parameter modified by the computer based on renal function. The fraction of prescriptions deemed appropriate during the intervention vs control periods by dose was 67% vs 54% (P<.001) and by frequency was 59% vs 35% (P<.001). Mean (SD) length of stay was 4.3 (4.5) days vs 4.5 (4.8) days in the intervention vs control periods, respectively (P =.009). There were no significant differences in estimated hospital and pharmacy costs or in the proportion of patients who experienced a decline in renal function during hospitalization. CONCLUSIONS Guided medication dosing for inpatients with renal insufficiency appears to result in improved dose and frequency choices. This intervention demonstrates a way in which computer-based decision support systems can improve care.
Performance analysis of LoRa radio for an indoor IoT applications

LoRa is an emerging wireless standard specifically designed for Low Power Wide Area Networks (LPWANs). It provides long range, low data rate, and energy efficient wireless communication and is believed to have high potential for realization of a large number of Internet of Things (IoT) applications. Various research papers have already reported on the performance analysis of LoRaWAN protocol in terms of radio communication range, and reliability for outdoor environments, while performance analysis for indoor environments have not yet received enough attention. In this paper, we provide an in-depth performance evaluation of LoRa for indoor IoT applications.
The opinions of school principals on decentralization in education

Calismanin amaci, okul mudurlerinin egimde yerellesmeye iliskin goruslerinin belirlenmesidir. Calismada olgu bilim deseni kullanmistir. Calisma grubunun belirlenmesinde amacli ornekleme yontemlerinden olcut ornekleme ve kolay ulasilabilir durum orneklemesi birlikte kullanilmis olup alti okul muduru calisma grubuna alinmistir. Veriler yari-yapilandirilmis gorusme formunun kullanildigi bireysel yuz yuze gorusmelerle toplanmistir. Analiz surecinde betimsel analiz ve tumevarimsal icerik analizi yapilmistir. Sonuc olarak yerellesme kavramina iliskin goruslere butunsel acidan bakildiginda katilimcilarin cogunlugunun yerellesmeyi tam ozerklige yakin bulduklari gorulmektedir. Bu durum ise uniter devlet yapisi acisindan tehlikeli gorulmektedir. Bu nedenle, egitimde yerellesmeye iliskin gorusleri soruldugunda katilimcilarin egitim sisteminin yerellesmesine iliskin finansman ve altyapi destegi disinda daha merkeziyetci tutum sergiledikleri gorulmektedir. Bu durum aslinda egitimde yerellesmeye iliskin kaygilarin yuksek oldugunun bir gostergesidir. Katilimcilarda ulus devlet kimligimize ve egitimin milli yapisina zarar vermeyecek bir yerellesme anlayisinin hâkim oldugu soylenebilir.
Hydrogen peroxide preconditioning enhances the therapeutic efficacy of Wharton's Jelly mesenchymal stem cells after myocardial infarction.

BACKGROUND Exposure of cells to sublethal concentrations of hydrogen peroxide (H2O2) can alleviate subsequent oxidative stress-induced apoptosis. We assessed the effects of H2O2 preconditioning on the therapeutic potential of human umbilical cord Wharton's Jelly mesenchymal stem cells (WJ-MSCs) in a murine model of myocardial infarction. METHODS WJ-MSCs were incubated in the media for 2 hours with or without 200 µmol/L H2O2. Mice underwent left anterior descending coronary artery ligation, and received injection of phosphate buffered saline, 1×10(6) WJ-MSCs, or 1×10(6) H2O2 preconditioned WJ-MSCs 3 hours later via tail vein. Echocardiography was performed 0, 7, 14 and 28 days after surgery, and the mice were euthanized on day 28 for histological analysis. In vitro cytokine concentrations in the WJ-MSC cell supernatant were measured by enzyme-linked immunosorbent assay (ELISA). The effect of WJ-MSC cell supernatant on the migration and proliferation of endothelial cells were observed by transwell migration and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazoliumbromide (MTT) assays. RESULTS Echocardiographic measurements revealed a significant improvement in the left ventricular contractility of the WJ-MSCs-H2O2 group compared to the WJ-MSCs group. Histological analysis revealed increased neovascularization and reduced myocardial fibrosis in the WJ-MSCs-H2O2 group compared to the WJ-MSCs group. Pretreatment of WJ-MSCs with H2O2 increased the secretion of interleukin-6 (IL-6) into the cell culture supernatant by approximately 25-fold. The culture supernatant from WJ-MSCs-H2O2 significantly increased the migration and proliferation of endothelial cells; these effects could be blocked using an anti-IL-6 antibody. CONCLUSIONS This study demonstrates that H2O2 preconditioning significantly enhanced the therapeutic potential of WJ-MSCs, possibly by stimulating the production of IL-6 by WJ-MSCs, which may cause migration and proliferation of endothelial cells and increase neovascularization.
Therapeutic response to Cognitive Processing Therapy in White and Black female veterans with military sexual trauma-related PTSD

Abstract Cognitive Processing Therapy (CPT) is an evidence-based treatment (EBT) for posttraumatic stress disorder (PTSD) which has been validated for female veterans with military-related PTSD. Existing trials have enrolled predominantly White veterans with some studies documenting higher rates of early termination from EBTs among Black females when compared to White females. Data from a previously published randomized clinical trial were used to evaluate the effectiveness of CPT for Black female veterans with military sexual trauma (MST)-related PTSD. Reductions in PTSD symptom severity, number of sessions attended, and early termination rates were compared between Black (n = 20) and White (n = 16) female veterans. A hierarchical linear modeling approach was used, with PTSD symptom severity over the course of treatment and follow-up entered as a level-1 variable and race (Black or White) entered as a level-2 predictor. Piecewise growth curves analyses revealed that both Black and White female veterans experienced significant reductions in PTSD symptom severity over the course of treatment and gains were maintained up to 6 months post-treatment. Race was not found to be a significant predictor of change in the slope of PTSD symptom severity over the course of CPT treatment. Additionally, number of sessions attended and rates of early termination did not significantly differ based on race. Results suggest that CPT was a well-tolerated and effective psychotherapeutic treatment for this sample regardless of racial self-identification.
Characterization of MADS-domain transcription factor complexes in Arabidopsis flower development

Floral organs are specified by the combinatorial action of MADS-domain transcription factors, yet the mechanisms by which MADS-domain proteins activate or repress the expression of their target genes and the nature of their cofactors are still largely unknown. Here, we show using affinity purification and mass spectrometry that five major floral homeotic MADS-domain proteins (AP1, AP3, PI, AG, and SEP3) interact in floral tissues as proposed in the “floral quartet” model. In vitro studies confirmed a flexible composition of MADS-domain protein complexes depending on relative protein concentrations and DNA sequence. In situ bimolecular fluorescent complementation assays demonstrate that MADS-domain proteins interact during meristematic stages of flower development. By applying a targeted proteomics approach we were able to establish a MADS-domain protein interactome that strongly supports a mechanistic link between MADS-domain proteins and chromatin remodeling factors. Furthermore, members of other transcription factor families were identified as interaction partners of floral MADS-domain proteins suggesting various specific combinatorial modes of action.
Comparison of the efficacy of dihydropyridine calcium channel blockers in African American patients with hypertension. ISHIB Investigators Group. International Society on Hypertension in Blacks.

BACKGROUND Hypertension is a prevalent disease among African Americans, and successful treatment rates are low. Since calcium channel blockers are well-tolerated and efficacious in African Americans, we undertook this study to compare the efficacy, safety, and tolerability of 3 commonly prescribed calcium channel blockers: amlodipine besylate (Norvasc), nifedipine coat core (CC) (Adalat CC), and nifedipine gastrointestinal therapeutic system (GITS) (Procardia XL). METHODS One hundred ninety-two hypertensive patients across 10 study centers were randomly assigned to double-blind monotherapy with amlodipine besylate (5 mg/d), nifedipine CC (30 mg/d), or nifedipine GITS (30 mg/d) for 8 weeks. Patients not achieving therapeutic response after 4 weeks had their dose doubled for the next 4 weeks. The primary end point was a comparison of the average reduction (week 8 minus baseline) in 24-hour ambulatory diastolic blood pressure (DBP). Secondary end points included a comparison of average 24-hour ambulatory systolic blood pressure (SBP), office SBP or DBP reduction, responder rates, safety, and tolerability. RESULTS One hundred sixty-three patients were evaluable for efficacy after 8 weeks. There was no significant difference in the average 24-hour ambulatory DBP (-8.5, -9.0, and -6.1 mm Hg, respectively) or SBP (-14.3, -15.7, and -11.8 mm Hg, respectively) reduction. Average office SBP and DBP were reduced to a comparable degree (19-22 mm Hg [P =.50] and 12-14 mm Hg [P =.51], respectively). Responder rates (DBP <90 or reduced by > or = 10 mm Hg) were similar (P = .38). Discontinuation rates and adverse event frequency were distributed similarly across the 3 treatment groups. CONCLUSION The efficacy, safety, and tolerability of the 3 dihydropyridine calcium channel blockers are equivalent in African Americans with stages 1 and 2 hypertension.
Comparative Functional Study of the Viral Telomerase RNA Based on Natural Mutations*

Telomerase activity is present in most malignant tumors and provides a mechanism for the unlimited potential for division of neoplastic cells. We previously characterized the first identified viral telomerase RNA (vTR) encoded by the Marek's disease virus (MDV) (Fragnet, L., Blasco, M. A., Klapper, W., and Rasschaert, D. (2003) J. Virol. 77, 5985–5996). This avian herpesvirus induces T-lymphomas. We demonstrated that the vTR subunit of the oncogenic MDV-RB1B strain is functional and would be more efficient than its chicken counterpart, cTR, which is 88% homologous. We take advantage of the functionality of those natural mutant TRs to investigate the involvement of the mutations of vTR on its efficiency in a heterologous murine cell system and in a homologous in vitro system using the recombinant chicken telomerase reverse transcriptase. The P2 helix of the pseudoknot seems to be more stable in vTR than in cTR, and this may account for the higher activity of vTR than cTR. Moreover, the five adenines just upstream from the P3 helix of vTR may also play an important role in its efficiency. We also established that the substitution of a single nucleotide at the 3′-extremity of the H-box of the vaccine MDV-Rispens strain vTR resulted in a lack of its accumulation within the cell, especially in the nucleus, correlated with a decrease in telomerase activity.
Improving the Progress of Research & Development (R&D) Projects by Selecting an Optimal Alliance Structure and Partner Type

This paper extends the study of alliance governance structure by examining what alliance structure, coordination mechanisms and partner type best enhance the likelihood of Research and Development (R&amp;D) progress or performance. We specially focus on the coordination and interaction mechanism of alliances, through which we classify the alliance governance structures in order to reflect the more complex alliance types and contracts used in today's R&amp;D. Using data from 255 biopharmaceuticals between the years 2000 and 2004, we found that, ceteris paribus, a moderate degree of inter&#8208;partner interaction and a moderately complex (non&#8208;equity&#8208;based) alliance contract contributes more to a better R&amp;D alliance performance than those structures that are too simple or too organizationally embedded (e.g. equity joint ventures), which possibly increase the risk of misalignment and miscommunication between allies. In addition, due to the reduced opportunism and the diverse resource (e.g. technology) pooled in the alliance, allying with diverse organizational partners such as non&#8208;profit research institutes and universities is more likely to enhance the R&amp;D performance. Our findings provide insightful strategic implications to practitioners in designing an appropriate alliance governance structure and choosing the right partner type for a successful R&amp;D collaboration.
Birthweight, HIV exposure and infant feeding as predictors of malnutrition in Botswanan infants

BACKGROUND A better understanding of the nutritional status of infants who are HIV-Exposed-Uninfected (HEU) and HIV-Unexposed-Uninfected (HUU) during their first 1000 days is key to improving population health, particularly in sub-Saharan Africa. METHODS A cross-sectional study compared the nutritional status, feeding practices and determinants of nutritional status of HEU and HUU infants residing in representative selected districts in Botswana during their first 1000 days of life. Four hundred and thirteen infants (37.3% HIV-exposed), aged 6-24 months, attending routine child health clinics, were recruited. Anthropometric, 24-h dietary intake and socio-demographic data was collected. Anthropometric Z-scores were calculated using 2006 World Health Organization growth standards. Modelling of the determinants of malnutrition was undertaken using logistic regression. RESULTS Overall, the prevalences of stunting, wasting and being underweight were 10.4%, 11.9% and 10.2%, respectively. HEU infants were more likely to be underweight (15.6% versus 6.9%), (P < 0.01) and stunted (15.6% versus 7.3%), (P < 0.05) but not wasted (P = 0.14) than HUU infants. HEU infants tended to be formula fed (82.5%), whereas HUU infants tended to breastfeed (94%) for the first 6 months (P < 0.001). Significant predictors of nutritional status were HIV exposure, birthweight, birth length, APGAR (appearance, pulse, grimace, activity and respiration) score and mother/caregiver's education with little influence of socio-economic status. CONCLUSIONS HEU infants aged 6-24 months had worse nutritional status compared to HUU infants. Low birthweight was the main predictor of undernutrition in this population. Optimisation of infant nutritional status should focus on improving birthweight. In addition, specific interventions should target HEU infants aiming to eliminate growth disparity between HEU and HUU infants.