Miracle-dz/UniFAR-FTUs huggingface dataset:
Patient decision-making related to antirheumatic drugs in rheumatoid arthritis: the importance of patient trust of physician.

OBJECTIVE To explore how rheumatoid arthritis (RA) antirheumatic drug-specific knowledge and numeric literacy, patient trust in physician, and demographic and disease-related factors relate to the confidence of patient decision-making related to disease modifying antirheumatic drugs (DMARD). METHODS Data were analyzed from 628 randomly selected patients with RA receiving care in community rheumatology practices, who responded to a multicenter, cross-sectional mail survey. We used multiple regression models to predict patient confidence in DMARD decision-making related to their most recently initiated DMARD. RESULTS Significant positive correlation was found between confidence in DMARD decision and trust in physician, DMARD-specific knowledge, and disease duration, but not risk-related numeric literacy, sex, or education. Negative correlations were found with disease severity and current bother with DMARD side effects. A multiple linear regression model of confidence in DMARD decision had an overall R = 0.788, R2 = 0.620 (p < 0.001). The 4 dependent variables contributing significantly to the model were female sex, Medicaid insurance status, satisfaction with RA disease control, and trust in physician, with standardized beta = 0.077, -0.089, 0.147, and 0.687, respectively. CONCLUSION In this sample of community patients with RA, the patient trust in physician had substantially greater effect on confidence in DMARD decision than DMARD-specific knowledge, disease-related factors, or demographic characteristics.
Colorectal and anal cancer in HIV/AIDS patients: a comprehensive review

Highly active antiretroviral therapy (HAART) has significantly altered the epidemiology of cancer that is diagnosed in individuals who are infected with the human immunodeficiency virus (HIV). Studies have shown a dramatic decrease in the incidence of and mortality from AIDS-related malignancies (primarily Kaposi sarcoma and non-Hodgkin's lymphoma), while the incidence of and mortality from non-AIDS defining malignancies is on the rise. While the risk of colorectal cancer (CRC) in HIV-infected individuals is controversial and has received limited study, there has been accumulating evidence that suggests an increased risk of developing anal cancer (AC) during the HAART era. This article reviews the current literature reporting on CRC and AC in the HIV-infected population, with a specific on cancer: incidence, screening, clinical characteristics, and treatment outcomes.
The gene encoding the major proline transporter of Aspergillus nidulans is upregulated during conidiospore germination and in response to proline induction and amino acid starvation

In Aspergillus nidulans a highly specific l‐proline transporter is encoded by the prnB gene which is tightly linked to all other genes involved in proline catabolism. In mycelia, the expression of the prn structural genes is finely co‐regulated in response to proline induction and nitrogen/carbon catabolite repression. In this study we establish that prnB expression is also activated during germination of conidiospores. This activation persists until the development of 6 h‐old mycelia and it is independent of proline induction mediated by the pathway‐specific prnA gene product. We then show that, in mycelia, prnB transcription is activated in response to proline or histidine starvation. This process has two components: a prnA‐dependent and a prnA‐independent component. A cis‐acting element that conforms to the consensus target of the GCN4/CPC1 transcriptional activators mediating amino acid biosynthesis activation in other fungi is involved in the activation of prnB transcription in response to amino acid starvation. We also show that the stimulation of prnB expression in germinating conidiospores is not due exclusively to transient internal amino acid starvation occurring during the transition from conidiospore to mycelium. This is the first report that an amino acid transporter gene is upregulated during development and in response to amino acid starvation and specific amino acid induction.
The psychophysiology of selective attention and working memory in children with PPDNOS and/or ADHD

Objective: We examined whether children (8-11 years) diagnosed with Pervasive Developmental Disorder-Not Otherwise Specified (PDD-NOS) or AttentionDeficit/Hyperactivity Disorder (ADHD) showing primarily hyperactive behavior, differed in selective attention and working memory (WM) abilities. Methods: Healthy controls and children with ADHD, PDD-NOS or symptoms of both disorders (PDD/HD) (n=15 in each group) carried out a visual selective memory search task while their EEG was recorded from which event-related potentials were derived. Results: Compared to the control group, all patient groups made more omissions while hyperactive children also exhibited more false alarms. Regarding the process of WM-controlled search, significant group differences in ERP data were found between the control group and each of the clinical groups. Conclusions: The results point to less efficient WM-functioning in all patient groups. Whereas the clinical groups differed from each other at the behavioral level as measured by questionnaires, no distinction between the clinical groups could be made with respect to performance or ERP measures of WM capacity and selective attention. Significance: The results suggest that a possible differentiation in selectivity and working memory capacities between PDD-NOS and ADHD is hard to find. This may agree with clinical practice, where differential diagnosis is a subject of discussion. ERPs in Children with ADHD and/or PDD-NOS
The Concept of Curative Margin in Surgery for Bone and Soft Tissue Sarcoma

To clarify the safety margin in excision of bone and soft tissue sarcomas, a new evaluation method for surgical margins was drafted by the Bone and Soft Tissue Committee of the Japanese Orthopaedic Association in 1989. This new evaluation system was applied to 1329 patients with bone and soft tissue sarcomas, of whom 492 were excluded because of insufficient details, leaving 837 patients (901 surgeries) for the current study. Based on the results derived from analyzing these registered surgical margins, predictable safety margins under different conditions could be determined. When preoperative treatment is not done or is ineffective in high-grade sarcoma, a margin greater than 3 cm wide is necessary. When the preoperative modality is effective, a 2-cm wide margin is permissible. However, for recurrent sarcoma, whether low-grade or high-grade, a curative procedure is necessary. For low-grade sarcoma, obtaining an adequate wide margin is essential but partial marginal margins are acceptable at sites where barriers exist. When the margin is insufficient, radiotherapy should be used regardless of the tumor grade. Making a safety margin definitive through this system, an optimum treatment can be obtained and unnecessary adjunctive modalities can be avoided.
Different Developmental Patterns of Melanocortin MC3 and MC4 Receptor mRNA: Predominance of Mc4 in Fetal Rat Nervous System

Melanocortins are thought to be involved in neuronal development and regeneration. Proopiomelanocortin (POMC), the precursor of α‐melanocyte stimulating hormone (α‐MSH), γ‐MSH, ACTH, and β‐endorphin, becomes detectable in rat hypothalamic neurons from gestational day (E) 12.5. We recently described stage‐ and region‐specific ontogenetic patterns of binding sites for the α‐MSH analogue [125I]‐Nle4, d‐Phe7‐α‐MSH ([125I]‐NDP), with the first localizations in epithalamus and sympathetic chain at E13. [125I]‐NDP binds to all known melanocortin receptors, including MC3‐R and MC4‐R, the predominant melanocortin receptors in nervous system. To identify the receptor type expressed during ontogeny, the developmental pattern of MC3‐R and MC4‐R mRNA was investigated by in situ hybridization in fetuses and offspring of time‐pregnant Long Evans rats between E14 and postnatal day (P) 27. MC4‐R mRNA was found to be the predominant species during the entire fetal period. It was localized in all fetal areas exhibiting distinct [125I]‐NDP binding, starting with sympathetic ganglia and epithalamus (E14), and including sensory trigeminal nuclei (E16), dorsal motor nucleus of vagus (E16) and cranial nerve ganglia, inferior olive (E18) and cerebellum (E18), striatal regions (E16), and entorhinal cortex (E22). In contrast, MC3‐R mRNA was detectable only in the postnatal period, with a fast increase in expression in the ventromedial and arcuate nuclei. The early presence of MC4‐R mRNA in central and peripheral nervous system and transient regional peaks of mRNA expression, often concomitant with periods of neural network formation, suggest a role of this receptor type in early ontogeny. The MC3 receptor may be involved in analogous processes during postnatal development.
Prenatal Exposure to Estrogenic Compounds Alters the Expression Pattern of Platelet-Derived Growth Factor Receptors α and β in Neonatal Rat Testis: Identification of Gonocytes as Targets of Estrogen Exposure1

Abstract We examined the effects of maternal exposure to estrogens on platelet-derived growth factor (PDGF) receptor (PDGFR) expression in newborn rat testis. Pregnant rats were treated from gestation Day 14 to birth with corn oil containing diethylstilbestrol, bisphenol A, genistein, or coumestrol by gavage or subcutaneous injection. These treatments induced a dose-dependent increase in the expression of PDGFR α and β mRNAs, determined by semiquantitative reverse transcription polymerase chain reaction, though diethylstilbestrol had a biphasic effect on both mRNAs. In situ hybridization analysis showed that PDGFRα mRNA increased mostly in the interstitium, while PDGFRβ mRNA increased both in the interstitium and seminiferous cords. Immunohistochemical studies of PDGFRα and β proteins revealed that both receptors were present in testis before and after birth and that they were upregulated upon treatment with estrogens in 3-day-old rats, with PDGFRβ increasing dramatically in gonocytes. PDGFRα and β mRNAs and proteins were also found in purified gonocytes. Our previous finding that PDGF and 17β-estradiol induce gonocyte proliferation in vitro, together with the present finding that in vivo exposure to estrogens upregulates PDGF receptors in testis, suggest that PDGF pathway is a target of estrogens in testis. In addition, these data identify PDGFRβ in gonocytes as a major target of gestational estrogen exposure, suggesting that estrogen may have a physiological interaction with PDGF during gonocyte development. These results, however, do not exclude the possibility that the effects of the compounds examined in this study might be due to estrogen receptor-independent action(s).
Survival forests for data with dependent censoring

Tree-based methods are very powerful and popular tools for analysing survival data with right-censoring. The existing methods assume that the true time-to-event and the censoring times are independent given the covariates. We propose different ways to build survival forests when dependent censoring is suspected, by using an appropriate estimator of the survival function when aggregating the individual trees and/or by modifying the splitting rule. The appropriate estimator used in this paper is the copula-graphic estimator. We also propose a new method for building survival forests, called p-forest, that may be used not only when dependent censoring is suspected, but also as a new survival forest method in general. The results from a simulation study indicate that these modifications improve greatly the estimation of the survival function in situations of dependent censoring. A real data example illustrates how the proposed methods can be used to perform a sensitivity analysis.
The effects of direct and indirect road transport consignment in combination with feed withdrawal in young dairy calves

Male dairy calves may be transported from their farm of origin at a young age. This process may involve an extended period off feed and indirect consignment through an intermediate facility, prompting potential welfare concerns. To assess the impact of transport, 59 male Holstein-Friesian dairy calves (5–9 d old) were either (1) held in situ on farm (control); (2) transported for 6 h; (3) transported for 12 h; or (4) transported for 1 h to a holding facility where they were kept for 6 h and then transported for 5 h. All treatments included a 30-h period of feed (milk) withdrawal, and calf responses were measured over time from before their last feed until the completion of the study after the transport and feed withdrawal periods. Apart from increases in serum creatine kinase in calves transported for 12 h, transported calves generally did not differ in blood concentrations of glucose, beta-hydroxybutyrate, lactate, total protein or in packed cell volume, compared with controls (P>0·05). Calf responses to the indirect consignment treatment did not differ from those of other transported calves. Withdrawal of feed for 30 h caused calves to lose 6% of body weight; blood glucose varied from 3·96 mmol/l immediately before daily feeding to 5·46 mmol/l at 3 h post feeding, and then declined to 3·43 mmol/l at 30 h. Calves lay down for 22–32% of the time during transport, and did not show a rebound effect in lying behaviour post arrival in comparison with controls. Best practice transport of 6–12 h duration, including indirect consignment via a holding facility, did not significantly affect calf blood biochemistry and metabolism in comparison with untransported animals. However, extending the time off feed beyond the daily feeding interval resulted in reduced blood glucose concentrations, suggesting that time off feed needs to be carefully managed in young transported dairy calves.
Voltammetric determination of dipyrone using a N,N'-ethylenebis(salicylideneaminato)oxovanadium(IV) modified carbon-paste electrode

The preparation and electrochemical characterization of a carbon paste electrode modified with N,N'-ethylenebis(salicylideneiminato)oxovanadium(IV) complex ([VO(Salen)]) as well as its behavior as electrocatalyst toward the oxidation of dipyrone were investigated. The electrochemical behavior of the modified electrode and the electrooxidation of dipyrone were explored using cyclic voltammetry. The voltammetric response of the modified electrode is based on two reactions. One electrochemical related to the oxidation of the metallic center of the [VO(Salen)] and the other involving the chemical redox process involving the oxidized form of the complex and the reduced form of dipyrone. The best voltammetric response was observed for a paste composition of 25% (m/m) [VO(Salen)], KCl solution pH from 5.5 to 8.0 as the electrolyte and potential scan rate of 10 mV s-1 in the presence of dipyrone. A linear voltammetric response for dipyrone was obtained in the concentration range from 9.9 x 10-6 to 2.8 x 10-3 mol L-1, with a detection limit of 7.2 x 10-6 mol L-1. Among of several compounds tested as potential interference, only ascorbic acid presented some interference. The proposed electrode is useful for the quality control and routine analysis of dipyrone in pharmaceutical formulations.
Probing nonnucleoside inhibitor‐induced active‐site distortion in HIV‐1 reverse transcriptase by transient kinetic analyses

Nonnucleoside reverse transcriptase inhibitors (NNRTI) are a group of structurally diverse compounds that bind to a single site in HIV‐1 reverse transcriptase (RT), termed the NNRTI‐binding pocket (NNRTI‐BP). NNRTI binding to RT induces conformational changes in the enzyme that affect key elements of the polymerase active site and also the association between the two protein subunits. To determine which conformational changes contribute to the mechanism of inhibition of HIV‐1 reverse transcription, we used transient kinetic analyses to probe the catalytic events that occur directly at the enzyme's polymerase active site when the NNRTI‐BP was occupied by nevirapine, efavirenz, or delavirdine. Our results demonstrate that all NNRTI–RT–template/primer (NNRTI–RT–T/P) complexes displayed a metal‐dependent increase in dNTP binding affinity (Kd) and a metal‐independent decrease in the maximum rate of dNTP incorporation (kpol). The magnitude of the decrease in kpol was dependent on the NNRTI used in the assay: Efavirenz caused the largest decrease followed by delavirdine and then nevirapine. Analyses that were designed to probe direct effects on phosphodiester bond formation suggested that the NNRTI mediate their effects on the chemistry step of the DNA polymerization reaction via an indirect manner. Because each of the NNRTI analyzed in this study exerted largely similar phenotypic effects on single nucleotide addition reactions, whereas each of them are known to exert differential effects on RT dimerization, we conclude that the NNRTI effects on subunit association do not directly contribute to the kinetic mechanism of inhibition of DNA polymerization.
Supplemental oxygen reduces the incidence of postoperative nausea and vomiting.

BACKGROUND Despite new anesthetic drugs and antiemetics, particularly 5-hydroxytryptamines, the incidence of postoperative nausea or vomiting remains between 20% and 70%. The authors tested the hypothesis that supplemental perioperative oxygen administration reduces the incidence of postoperative nausea or vomiting. METHODS Patients undergoing colon resection were anesthetized with fentanyl and isoflurane. During and for 2 h after surgery they were randomly assigned to (1) 30% oxygen, balance nitrogen (n = 119); or (2) 80% oxygen, balance nitrogen (n = 112). The incidence of nausea or vomiting during the first 24 postoperative hours was evaluated by nurses blinded to group assignment and oxygen concentration. Data were analyzed with unpaired t or Mann-Whitney U tests. Results are presented as means +/- SD; P < 0.05 was considered significant. RESULTS Factors known to influence nausea and vomiting were comparable in the two groups. Perioperative oxygen saturation was well within normal limits in each treatment group; saturations the first postoperative morning were comparable in each group. Supplemental oxygen reduced the incidence of postoperative nausea or vomiting from 30% in the patients given 30% oxygen to 17% in those given 80% oxygen (P = 0.027). CONCLUSIONS Supplemental oxygen reduced the incidence of postoperative nausea or vomiting nearly twofold after colorectal surgery. The mechanism by which oxygen administration reduces the incidence of these postoperative sequelae remains unknown but may be related to subtle intestinal ischemia. Because oxygen is inexpensive and essentially risk-free, supplemental oxygen appears to be an effective method of reducing postoperative nausea and vomiting.
Can Macroeconomists Get Rich Nowcasting Output Gap Turning Points with a Simple Machine-Learning Algorithm?

To nowcast economic turning points, probabilistic indicators are created from a simple and transparent machine-learning algorithm known as Learning Vector Quantization (LVQ). The real-time ability of the indicators to quickly and accurately detect economic turning points in the United States and in the euro area is gauged. To assess the value of the indicators, profit maximization measures based on trading strategies are employed in addition to more standard criteria. When comparing predictive accuracy and profit measures, the model confidence set procedure proposed by Hansen et al. (2011) is applied to avoid data snooping. A substantial improvement in profit measures over the benchmark is found: macroeconomists can get rich nowcasting economic turning points.
Prescription of Twice-Weekly Hemodialysis in the USA

Background/Aims: The purpose of this study was to investigate the frequency and characteristics of two hemodialysis sessions/week, to identify factors which influence or predict this prescription, and to examine the outcomes of patients receiving hemodialysis two times/week as compared to the more common treatment of three times/week. Methods: Data from a national sample of 15,067 adult hemodialysis patients were utilized to compare twice-weekly with thrice-weekly therapy by logistic regression. Results: Patients treated less than one year were more likely to be treated twice-weekly (6.1%) than patients on dialysis for one year or more (2.7%) (AOR = 1.49, p = 0.002). Treatment schedules also varied significantly by geographic region. Factors predictive of twice-weekly hemodialysis (p < 0.05) were older age, Caucasian race, female gender, higher serum albumin, lower serum creatinine levels, and lower body mass index. A higher estimated renal function at the start of ESRD was also predictive of a twice-weekly schedule among incident patients (AOR = 1.05, p = 0.05). In addition, Cox-adjusted survival analysis indicated a lower mortality risk (RR = 0.76, p = 0.02) for twice-weekly hemodialysis compared to thrice-weekly among prevalent patients. For incident patients, however, the results were not significant when adjusted for GFR at ESRD onset (RR = 0.85, p = 0.31). Conclusion: Geographic differences in prescribed treatment remained unexplained by measured characteristics. The survival advantage associated with twice-weekly hemodialysis is likely to be related to patient selection and greater residual renal function.
Antimalarial Activity of Small-Molecule Benzothiazole Hydrazones

ABSTRACT We synthesized a new series of conjugated hydrazones that were found to be active against malaria parasite in vitro, as well as in vivo in a murine model. These hydrazones concentration-dependently chelated free iron and offered antimalarial activity. Upon screening of the synthesized hydrazones, compound 5f was found to be the most active iron chelator, as well as antiplasmodial. Compound 5f also interacted with free heme (KD [equilibrium dissociation constant] = 1.17 ± 0.8 μM), an iron-containing tetrapyrrole released after hemoglobin digestion by the parasite, and inhibited heme polymerization by parasite lysate. Structure-activity relationship studies indicated that a nitrogen- and sulfur-substituted five-membered aromatic ring present within the benzothiazole hydrazones might be responsible for their antimalarial activity. The dose-dependent antimalarial and heme polymerization inhibitory activities of the lead compound 5f were further validated by following [3H]hypoxanthine incorporation and hemozoin formation in parasite, respectively. It is worth mentioning that compound 5f exhibited antiplasmodial activity in vitro against a chloroquine/pyrimethamine-resistant strain of Plasmodium falciparum (K1). We also evaluated in vivo antimalarial activity of compound 5f in a murine model where a lethal multiple-drug-resistant strain of Plasmodium yoelii was used to infect Swiss albino mice. Compound 5f significantly suppressed the growth of parasite, and the infected mice experienced longer life spans upon treatment with this compound. During in vitro and in vivo toxicity assays, compound 5f showed minimal alteration in biochemical and hematological parameters compared to control. In conclusion, we identified a new class of hydrazone with therapeutic potential against malaria.