Miracle-dz/UniFAR-FTUs huggingface dataset:
Effects of the ABCB1 c.3435C>T (rs1045642) Polymorphism on Heat Pain Perception in Opioid-Free Adults With Chronic Pain

BACKGROUND: The adenosine triphosphate-binding cassette, subfamily B, member 1 gene (ABCB1) encodes P-glycoprotein (P-gp) that influences the intracellular transport of solutes including endogenous opioid peptides. The primary objective of this study was to determine the effects of the ABCB1 polymorphism c.3435C>T (rs10454642) on heat pain (HP) perception in a group of opioid-free adults with chronic pain. METHODS: Opioid-free adults with chronic pain consecutively admitted to a pain rehabilitation program comprised the study cohort (N = 134). Individuals were genotyped for the c.3435C>T (rs10454642) polymorphism. The polymorphism was analyzed with nonparametric tests using a dominant (cytosine-cytosine [CC] versus cytosine-thymine [CT] + thymine-thymine [TT]) and recessive (CC + CT versus TT) model of allele effects. Quantitative sensory testing was performed using the Computer Aided Sensory Evaluator IV system. RESULTS: The distribution of genotypes was 22% (N = 29) for CC, 45% (N = 60) for CT, and 33% (N = 45) for TT (Hardy-Weinberg, P > .1). A significant association was observed between the recessive model and HP threshold. Standardized values of HP threshold were significantly greater in the TT group than the CC + CT group (median difference, −0.77; 95% confidence interval [CI], −1.49 to −0.23; P = .005), and the effect size estimate was small (Cliff delta = 0.30). In the dominant model, no significant difference in HP threshold was observed between the CC and CT + TT groups (median difference, −0.45; 95% CI, −1.15 to 0.00; P = .108). CONCLUSIONS: These results posit that the efflux of endogenous opioid peptides is reduced in individuals with the TT genotype due to lower expression of P-gp, which, in turn, results in higher HP threshold. This study contributes to the emerging understanding of how the ABCB1 c.3435C>T polymorphism contributes to pain perception in opioid-free adults with chronic pain and provides the foundation for investigating the potential effects of this polymorphism on the clinical course of chronic pain.
The Impact of Rivaroxaban and Apixaban on Tacrolimus Trough Levels

The solid organ transplant community is slow to adopt the routine practice of using direct oral anticoagulants. Rivaroxaban and apixaban share common metabolic pathways with tacrolimus. This study aimed to clarify the impact of rivaroxaban/apixaban on tacrolimus troughs. Fifty solid organ transplant recipients with concomitant use of tacrolimus and rivaroxaban/apixaban were retrospectively assessed for changes in tacrolimus troughs and dose. Average dose-adjusted tacrolimus troughs and average tacrolimus total daily doses prior to and after rivaroxaban/apixaban initiation were compared. Subgroup analyses evaluating rivaroxaban and apixaban individually were performed. Rivaroxaban was prescribed to 18 recipients, and apixaban was prescribed to 32 recipients. Transplanted organs included kidney (n = 22), lung (n = 18), liver (n = 7), simultaneous pancreas and kidney (n = 1), and simultaneous kidney and liver (n = 2). The median doseadjusted tacrolimus trough and tacrolimus total daily dose prior to rivaroxaban/apixaban initiation was 2.15 ng/mL/mg (IQR 1.17, 3.37) and 4 mg (IQR 1.88, 6.25), respectively. The median dose-adjusted tacrolimus trough and tacrolimus total daily dose after rivaroxaban/apixaban initiation was 2.16 ng/mL/mg (IQR 1.24, 4.10) and 3.55 mg (IQR 1.5, 6.35), respectively. No significant difference was found between average dose-adjusted tacrolimus troughs or tacrolimus total daily doses before and after rivaroxaban/apixaban initiation or in the individual subgroup analyses for rivaroxaban/apixaban. It is unlikely that initiating rivaroxaban/apixaban affects tacrolimus troughs or requires tacrolimus dose adjustment. This study does not elucidate if tacrolimus affects rivaroxaban/apixaban pharmacokinetics or pharmacodynamics.
HPV-Induced Oropharyngeal Squamous Cell Carcinomas in Brazil: Prevalence, Trend, Clinical, and Epidemiologic Characterization

Background: Tobacco or human papillomavirus (HPV)-related oropharyngeal squamous cell carcinomas (OPSCC) represent different clinical and epidemiologic entities. This study investigated the prevalence of HPV-positive and HPV-negative OPSCC in a reference cancer hospital in Brazil and its association with clinical and demographic data, as well as its impact on overall survival. Methods: HPV infection was determined by p16-IHC in pre-treatment formalin-fixed paraffin-embedded samples from all patients with OPSCC diagnosed at Barretos Cancer Hospital between 2008 and 2018. The prevalence of HPV-positive cases and its temporal trend was assessed, and the association of clinical and demographic data with HPV infection and the impact on patient overall survival was evaluated. Results: A total of 797 patients with OPSCC were included in the study. The prevalence of HPV-associated tumors in the period was 20.6% [95% confidence interval, 17.5–24.0] with a significant trend for increase of HPV-positive cases over the years (annual percentage change = 12.87). In a multivariate analysis, the variables gender, level of education, smoking, tumor sublocation, region of Brazil, and tumor staging had a significant impact in HPV positivity, and a greater overall survival (OS) was observed in HPV-positive patients (5-year OS: 47.9% vs. 22.0%; P = 0.0001). Conclusions: This study represents the largest cohort of Brazilian patients with OPSCC characterized according to HPV status. We report significant differences in demographics and clinical presentation according to HPV status, and an increasing trend in prevalence for HPV-induced tumors. Impact: These findings can potentially contribute to a better stratification and management of patients as well as assist in prevention strategies.
The prevalence of depressive disorder and its association in Thai cervical cancer patients

Purpose The purpose of this study is to examine the prevalence, associated factors and quality of life associated with depressive disorder in cervical cancer patients. Patients and methods This cross-sectional study was carried out in a gynecologic oncology clinic of a university hospital in Northern Thailand from October 2018 to August 2019. Two-hundred cervical cancer patients were screened for depressive disorder using the nine-item Patient Health Questionnaire (PHQ-9), and psychiatrists interviewed eligible patients to confirm diagnoses. We measured the quality of life using questionnaires from the European Organisation for the Research and Treatment of Cancer: Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) and Cervical Cancer Module 24 (EORTC QLQ-Cx24). Associated factors, including comorbidity, fatigue, and pain, were collected using the Charlson Comorbidity Index (CCI), the eleven-item Chalder Fatigue Scale (CFQ 11), and the visual analog scale (VAS) for pain, respectively. Results Twenty-seven (13.5%) cervical cancer patients were diagnosed with depressive disorder by psychiatrists according to the DSM-5. Depressive disorder was related to a worse quality of life in these patients. A binary logistic regression analysis revealed that depressive disorder among these patients was linked with these factors: high fatigue score (aOR: 1.35; CI: 1.18–1.53), high pain score (aOR: 1.25; CI: 1.02–1.54), no perception of social support, (aOR: 3.12; CI: 1.11–8.81), and no previous surgical treatment for cervical cancer (aOR: 2.99; CI: 1.08–8.29). Conclusion The depressive disorder prevalence was 13.5% in Northern Thai cervical cancer patients. In this demographic, cervical cancer patients—who reported high fatigue or pain scores, did not perceive social support, or had no previous cervical cancer surgery- were more likely to have depressive disorder.
Review and analysis of personal-ambient ozone measurements

ABSTRACT Ambient ozone measurements are often used as surrogates for personal exposures. Due to the limited number of central ozone monitors and varying personal behavioral patterns, some level of variability between ambient and personal exposures is expected. Low-cost sensors and different ways to capture personal activity patterns are being developed as an effort to improve the accuracy of exposure assessment. However, it is still most common to use the traditional approach of using unadjusted ambient concentrations as surrogates for personal exposures. To our knowledge, there has not been a meta-analysis that summarizes the findings from studies that investigated the differences between personal and ambient ozone. We conducted a literature search in PubMed and Science Direct for peer-reviewed studies reporting at least one of the following in a numeric format: 1) personal-ambient measurements, 2) personal-ambient slopes, or 3) personal-ambient correlations to identify and summarize existing studies that investigated personal and ambient ozone concentrations. Twenty-two articles met inclusion criteria and were included in our review. Ambient concentrations almost always overestimated personal exposures. A meta-analysis of slopes showed an overall personal-ambient slope of 0.21 (95% CI: 0.15, 0.27) with high heterogeneity (97%) across studies. The correlations between personal and ambient ozone varied dramatically across subjects from a strong positive (0.77) to a moderate negative correlation (−0.43). Our study found that ambient measurements are not accurate representations of personal exposure, while the magnitude of exposure measurement error varied across studies. Different sources of ozone and how they contribute to true exposure levels for individuals in complementary ways need to be better addressed. The effort to better understand the impact of traditional exposure assessment on the risk estimates must be emphasized along with efforts to improve the current exposure assessment approaches to provide context for interpreting the results from ozone epidemiological studies. Implications: The traditional approach of using ambient ozone measurements as surrogates for personal exposures is likely to result in exposure misclassification, which is a well-recognized source of bias in epidemiological studies. There are efforts to characterize the differences between ambient and personal ozone measurements, though, to our knowledge, there has not been a meta-analysis that summarizes the findings of different studies. Better understanding of the pattern and magnitude of exposure error for ambient and personal ozone can provide directions for future studies and context for interpreting the results from ozone epidemiological studies.
Measurement Uncertainty and Conformity Assessment Applied to Drug and Medicine Analyses – A Review

Abstract Analytical results are often used in scientific research, industrial and clinical applications to support decision making. Despite all efforts to ensure the reliability of analytical results (including method validation, internal quality control, use of certified reference materials, proficiency tests, and ISO 17025 accreditation), there will always be an uncertainty associated with the measured value. The measurement uncertainty expresses the quality of the analytical result and allows the comparability between analytical results or between the measured value and the specification limit(s). This work discusses the importance of measurement uncertainty, including the steps involved in the measurement uncertainty evaluation, the bottom-up and top-down approaches used in measurement uncertainty calculation, the measurement uncertainty evaluation in drug and medicine analyses, and the application of measurement uncertainty in conformity assessment for quality control, stability studies, and pharmaceutical equivalence.
DPP: Deep predictor for price movement from candlestick charts

Forecasting the stock market prices is complicated and challenging since the price movement is affected by many factors such as releasing market news about earnings and profits, international and domestic economic situation, political events, monetary policy, major abrupt affairs, etc. In this work, a novel framework: deep predictor for price movement (DPP) using candlestick charts in the stock historical data is proposed. This framework comprises three steps: 1. decomposing a given candlestick chart into sub-charts; 2. using CNN-autoencoder to acquire the best representation of sub-charts; 3. applying RNN to predict the price movements from a collection of sub-chart representations. An extensive study is operated to assess the performance of the DPP based models using the trading data of Taiwan Stock Exchange Capitalization Weighted Stock Index and a stock market index, Nikkei 225, for the Tokyo Stock Exchange. Three baseline models based on IEM, Prophet, and LSTM approaches are compared with the DPP based models.
Sex Differences in Prehospital Delays in Patients With ST‐Segment–Elevation Myocardial Infarction Undergoing Percutaneous Coronary Intervention

Background Women with ST‐segment–elevation myocardial infarction experience delays in reperfusion compared with men with little data on each time component from symptom onset to reperfusion. This study analyzed sex discrepancies in patient delays, prehospital system delays, and hospital delays. Methods and Results Consecutive patients with ST‐segment–elevation myocardial infarction treated with percutaneous coronary intervention across 30 hospitals in the Victorian Cardiac Outcomes Registry (2013–2018) were analyzed. Data from the Ambulance Victoria Data warehouse were used to perform linkage to the Victorian Cardiac Outcomes Registry for all patients transported via emergency medical services (EMS). The primary end point was EMS call‐to‐door time (prehospital system delay). Secondary end points included symptom‐to‐EMS call time (patient delay), door‐to‐device time (hospital delay), 30‐day mortality, major adverse cardiovascular events, and major bleeding. End points were analyzed according to sex and adjusted for age, comorbidities, cardiogenic shock, cardiac arrest, and symptom onset time. A total of 6330 (21% women) patients with ST‐segment–elevation myocardial infarction were transported by EMS. Compared with men, women had longer adjusted geometric mean symptom‐to‐EMS call times (47.0 versus 44.0 minutes; P<0.001), EMS call‐to‐door times (58.1 versus 55.7 minutes; P<0.001), and door‐to‐device times (58.5 versus 54.9 minutes; P=0.006). Compared with men, women had higher 30‐day mortality (odds ratio [OR], 1.38; 95% CI, 1.06–1.79; P=0.02) and major bleeding (OR, 1.54; 95% CI, 1.08–2.20; P=0.02). Conclusions Female patients with ST‐segment–elevation myocardial infarction experienced excess delays in patient delays, prehospital system delays, and hospital delays, even after adjustment for confounders. Prehospital system and hospital delays resulted in an adjusted excess delay of 10 minutes compared with men.
Neural mechanisms of psychosis vulnerability and perceptual abnormalities in the ALS‐FTD spectrum

The aims of this study were to (i) explore psychotic experiences across the entire amyotrophic lateral sclerosis‐frontotemporal dementia (ALS‐FTD) spectrum from a clinical and genetic perspective, (ii) determine the rate of abnormal perceptual experiences across the five sensory modalities and (iii) explore the neurobiological factors that lead to psychosis vulnerability in ALS‐FTD.
Multitissue 2H/13C flux analysis reveals reciprocal upregulation of renal gluconeogenesis in hepatic PEPCK-C–knockout mice

The liver is the major source of glucose production during fasting under normal physiological conditions. However, the kidney may also contribute to maintaining glucose homeostasis in certain circumstances. To test the ability of the kidney to compensate for impaired hepatic glucose production in vivo, we developed a stable isotope approach to simultaneously quantify gluconeogenic and oxidative metabolic fluxes in the liver and kidney. Hepatic gluconeogenesis from phosphoenolpyruvate was disrupted via liver-specific knockout of cytosolic phosphoenolpyruvate carboxykinase (PEPCK-C; KO). 2H/13C isotopes were infused in fasted KO and WT littermate mice, and fluxes were estimated from isotopic measurements of tissue and plasma metabolites using a multicompartment metabolic model. Hepatic gluconeogenesis and glucose production were reduced in KO mice, yet whole-body glucose production and arterial glucose were unaffected. Glucose homeostasis was maintained by a compensatory rise in renal glucose production and gluconeogenesis. Renal oxidative metabolic fluxes of KO mice increased to sustain the energetic and metabolic demands of elevated gluconeogenesis. These results show the reciprocity of the liver and kidney in maintaining glucose homeostasis by coordinated regulation of gluconeogenic flux through PEPCK-C. Combining stable isotopes with mathematical modeling provides a versatile platform to assess multitissue metabolism in various genetic, pathophysiological, physiological, and pharmacological settings.
Cost-effective fabrication of high-performance flexible all-solid-state carbon micro-supercapacitors by blue-violet laser direct writing and further surface treatment

A facile and cost-effective method for the fabrication of all-solid-state flexible carbon micro-supercapacitors (MSC) was demonstrated by laser direct writing on polyimide (PI) sheets with a compact and low-cost 405 nm semiconductor blue-violet laser, the beam of which was almost totally absorbed in the PI sheet. The obtained MSCs exhibit high performances due to the hierarchical porous structures and large thickness. Furthermore, surface treatment by air-plasma etching was employed to improve the contact interface between the carbon structures and the electrolyte, which may also influence pore structures, thus largely enhancing the MSC performance. The typical MSCs after plasma treatment for 100 s show an improved specific capacitance as high as 18.3 mF cm−2 at a scan rate of 10 mV s−1 and 31.9 mF cm−2 at a current density of 0.05 mA cm−2, both of which are higher than most of the carbon material-based MSCs reported till now. Moreover, the MSCs show good flexibility, long-time cycle stability, as well as temperature tolerance up to 80 °C. In addition, the voltage and capacitance can be scaled up by simply connecting a single MSC in series, parallel or both. The facile fabrication, low cost, and good performance make carbon-based MSCs fabricated by semiconductor laser direct writing promising candidates for on-chip energy storage devices.
Socio-cognitive engagement (but not socioeconomic status) predicts preschool children's language and pragmatic abilities

Abstract Parental socioeconomic status (SES) strongly influences children's language abilities but less is known about its influence on pragmatic abilities (e.g., inferring intentions from relevance implicatures). Moreover, by focussing on SES, the role of socio-cognitive engagement (e.g., joint parent-child interactions) has been overlooked. We tested four- and six-year-old children (n = 92) with a communication task, a questionnaire assessed parents’ SES and socio-cognitive engagement. Socio-cognitive engagement predicted children's communication abilities while the parental educational background and income did not. This emphasizes the notion that communication is a highly socio-cognitive task, one which children perform the better the more frequently they engage in socio-cognitive interactions.
How important is dietary management in chronic kidney disease progression? A role for low protein diets

High dietary protein intake may lead to increased intraglomerular pressure and glomerular hyperfiltration, which in the long-term can lead to de novo or aggravating preexisting chronic kidney disease (CKD). Hence, a low protein diet (LPD, 0.6 to 0.8 g/kg/day) is recommended for the management of CKD. There are evidences that dietary protein restriction mitigate progression of CKD and retard the initiation of dialysis or facilitate incremental dialysis. LPD is also helpful to control metabolic derangements in CKD such as metabolic acidosis and hyperphosphatemia. Recently, a growing body of evidence has emerged on the benefits of plant-dominant low-protein diet (PLADO), which composed of > 50% plant-based sources. PLADO is considered to be helpful for relieving uremic burden and metabolic complications in CKD compared to animal protein dominant consumption. It may also lead to favorable alterations in the gut microbiome, which can modulate uremic toxin generation along with reducing cardiovascular risk. Alleviation of constipation in PLADO may minimize the risk of hyperkalemia. A balanced and individualized dietary approach for good adherence to LPD utilizing various plant-based sources as patients’ preference should be elaborated for the optimal care in CKD. Periodic nutritional assessment under supervision of trained dietitians should be warranted to avoid protein-energy wasting.
Neuregulin1-ErbB4 signaling mediates synaptic maturation and induces dendritic branching in hippocampal neurons

Central nervous system (CNS) synapse formation is a complex process that ensures precise alignment, as well as complementarity of the presynaptic and postsynaptic components. Numerous players are involved in different stages of CNS synaptogenesis, however, the list is far from complete. Neuregulin-1 (NRG1) and its receptor ErbB4 tyrosine kinase are widely expressed in the developing and adult brain. ErbB4 is specifically expressed in inhibitory GABAergic interneurons. Moreover, ErbB4 is localized to synapses and associates through it PDZ-binding motif with the postsynaptic density protein PSD-95, a major scaffolding protein involved in glutamatergic synapse stabilization and maturation. Given its location, ErbB4 is capable to take part in synapse development in GABAergic interneurons; however, little is known of its function at the synapse. In the following work, we manipulated levels of ErbB4 protein expression in primary hippocampal neuron cultures to determine the role of ErbB4 at the synapse. We found that cells overexpressing the receptor formed larger excitatory and inhibitory presynaptic terminals, while the number of synapses per unit length remained the same. This process did not depend on the kinase domain activity. Moreover, highly clustered exogenous ErbB4 recruited PSD-95 to the site of the synapse, a process dependent on the PDZ interaction, since deletion of the PDZbinding motif severely perturbed ErbB4 localization. However, ErbB4 is not a synapse inducing factor, since expression in heterologous cells failed to induce presynaptic differentiation.
Counteracting subliminal cues that threaten national identity

In spite of their subtle nature, subliminal cues of group devaluation can have profound effects on members of targeted groups. Across three studies, we examine factors that allow people to counteract subliminal cues of group devaluation. We do this in the context of Spanish–German intergroup relations following the 2008 financial crisis. Throughout the crisis, narratives in politics and the media have drawn on national stereotypes to legitimize the economic situation in Spain. We argue that this represents a threat to our Spanish participants and that exposure to subliminal cues that reflect this threat will trigger responses that counteract this threat. Indeed, results showed that when subliminal associations legitimize the disadvantage faced by the group, our Spanish participants reversed the subliminal associations to which they were exposed. These findings show that Spanish participants are able to counteract the devaluation of their national in‐group, even when that devaluation occurs outside of conscious awareness.