Miracle-dz/UniFAR-FTUs huggingface dataset:
Exploring Differences in Pharmacometrics of Rabeprazole between Genders via Population Pharmacokinetic–Pharmacodynamic Modeling

Rabeprazole is a proton pump inhibitor that inhibits gastric acid production and increases gastric pH; it is widely used clinically as a treatment option for gastritis and gastric ulcers. However, information on the inter-individual variability of rabeprazole pharmacometrics, which is a key element in establishing its scientific clinical use, is still lacking. Particularly, the differences in pharmacokinetics between genders and the degree of variation in pharmacodynamics have not been clearly identified. Thus, the main purpose of this study was to explore any differences in rabeprazole pharmacokinetics between genders and to quantitatively predict and compare the effects of any differences in pharmacokinetics between genders on known pharmacodynamics using population pharmacokinetic–pharmacodynamic modeling. To compare pharmacokinetics and modeling data between genders, bioequivalence results were used simultaneously on healthy Korean men and women using the physiological and biochemical parameters derived from each individual. Pharmacodynamic modeling was performed based on the data of previously reported gastric pH changes in response to rabeprazole plasma concentrations, which was co-linked to the central compartmental bioavailable concentration in the population pharmacokinetic model. There was no significant difference in the level of rabeprazole exposure and elimination of plasma between genders following oral administration of 10 mg enteric-coated rabeprazole tablets; however, there was a clear delay in absorption in women compared to men. Additionally, a comparison of pharmacokinetic parameters normalized to body weight between genders showed that the maximum plasma concentrations were significantly higher in women than in men, again suggesting gender differences in rabeprazole absorption. The population pharmacokinetic profiles for rabeprazole were described using a three-sequential multi-absorption with lag time (Tlag) two-compartment model, whereas body surface area and gender were explored as effective covariates for absorption rate constant and Tlag, respectively. The effect of increased gastric pH due to plasma exposure to rabeprazole was explained using the Sigmoid Emax model, with the baseline as a direct response. The significantly longer rabeprazole Tlag in females delayed the onset of an effect by an average of 1.58 times (2.02–3.20 h), yet the overall and maximum effects did not cause a significant difference within 15%. In the relative comparison of the overall efficacy of rabeprazole enteric-coated tablet administration between genders, it was predicted based on the model that males would have higher efficacy. This study will be very useful in broadening the perspective of interpreting drug diversity between individuals and narrowing the gap in knowledge related to scientific precision medicine by presenting new information on gender differences in rabeprazole pharmacometrics that had not been previously identified.
Geochemistry and Pb,Sr,Nd isotopic features of ore-bearing porphyries in Bangong Lake porphyry copper belt,western Tibet

Detailed geochemical and Pb,Sr,Nd isotopic researches on the Duobuza copper deposit and the Garqiong copper deposit were conducted in the Bangong Lake copper belt.The result shows that,compared with the porphyries of the Gandese copper belt,the ore-bearing porphyries of the Bangong Lake copper belt are weaker in the enrichment of large ion lithophile elements (LILE) and are also weaker in the depletion of high-field strength elements and high rare elements,thus having weak positive Eu anomaly.Viewed from Pb,Sr,Nd isotopic features,the ore-bearing porphyries are characterized by the enrichment of radiogenic Pb,the obviously low ratios of 143Nd/144Nd,and the source nearer to the Indian Ocean sedimentary area,indicating that the magma source of the ore-bearing porphyries is much shallower,with the mixture of more crustal materials.The forming tectonic environment of the ore-bearing porphyries in the Bangong Lake copper belt belonged to the active continental ridge,whereas that in the Gangdese copper belt was far away from the active continental ridge.The Bangong Lake porphyry copper belt was formed in a post-collisional crustal up-lift stage,whereas the Gangdise porphyry copper belt in a stage of post-collisional crustal extensional collapse when the crust rose to the maximum height.
Evaluation of Thermal Antinociceptive Effects of Intramuscular Hydromorphone Hydrochloride in Great Horned Owls (Bubo virginianus)

Abstract: Across the Americas, great horned owls (Bubo virginianus) are often presented to veterinarians for conditions requiring pain management. Although recent studies have evaluated opioid drugs in raptor species, information in Strigiformes is lacking. The objective of this study was to evaluate the analgesic effect and duration of action of hydromorphone hydrochloride, a full µ-opioid receptor agonist, in great horned owls. In a randomized, blinded, balanced crossover study, 6 adult birds (5 females and 1 male) received hydromorphone (0.3 and 0.6 mg/kg) or saline (0.9% NaCl) solution (0.03 mL/kg; control) in the left pectoral muscle, with a 7-day washout interval between treatments. Each bird was assigned an agitation-sedation score, and the thermal foot withdrawal threshold (TFWT) was measured at predetermined times before (t = 0 hours) and after treatment administration (t = 0.5, 1.5, 3, and 6 hours). Measurements of the TFWT were obtained with a test box equipped with a thermal perch, which delivered a gradually increasing temperature 40–62°C (104–143.6°F) to the right plantar surface of the owl's foot. Compared with controls, hydromorphone at 0.3 mg/kg dose resulted in significantly higher mean TFWT at 0.5 hours (P < 0.001), 1.5 hours (P = 0.003), and 3 hours (P = 0.005), whereas the 0.6 mg/kg dose resulted in significantly higher mean TFWT from 0.5 hours (P = 0.035) to 1.5 hours (P = 0.001). Both hydromorphone doses were associated with a significant change in the agitation-sedation score (P = 0.001), consistent with mild to moderate sedation. Two owls were observed tremoring after administration of the 0.6 mg/kg dose, which was not noted after the 0.5-hour timepoint; no other adverse effects were identified. This study offers scientific evidence to support the use of a µ-opioid agonist in great horned owls for pain management. Pharmacokinetics and other pharmacodynamic studies of other pain models evaluating hydromorphone and other opioid drugs in this species are still needed.
Swine wastewater associated with mineral fertilization in soybean (Glycine max L.) cultures: 9 th production cycle

Western Parana is a region characterized by intensive pig farming, where considerable amounts of wastes are produced daily, demanding techniques for the reduction, treatment and appropriate disposal of such residues. Many studies have shown the potential use of swine wastewaters as an alternative source of fertilization, which improves the crop yields and soil conditions. Thus, the objective of this study was to assess the long-term environmental and agricultural impacts of the application of wastewater associated with mineral fertilization in soybean crop and soil in the western region of Parana, Brazil, in an area with a history of four years using the proposed treatments. The experiment was conducted at the Experimental Centre of Agricultural Engineering in twenty-four drainage lysimeters, where eight treatments using swine wastewater associated/not associated with mineral fertilizers were applied. The experimental design consisted of factorial (4 x 2) randomized blocks with three replications. The swine wastewater can be used as an alternative fertilizer for cultivation, since nitrogen, phosphorus, potassium and sulfur are supplemented with specific fertilization. Leaching of nitrite + nitrate, copper, iron, manganese, sodium and zinc must be given more attention in the soil, where these nutrients exceed the recommended limits.
Critical re-examination of known purported fossil Bombycoidea (Lepidoptera)

We critically re-examine 17 records of fossils currently assigned to the lepidopteran superfamily Bombycoidea, which includes the silk moths, emperor moths and hawk moths. These records include subfossils, compression and impression fossils, permineralizations and ichnofossils. We assess whether observable morphological features warrant their confident assignment to the superfamily. None of the examined fossils displays characters that allow unequivocal identification as Sphingidae, but three fossils and a subfossil (Mioclanis shanwangiana Zhang, Sun and Zhang, 1994, two fossil larvae, and a proboscis in asphaltum) have combinations of diagnostic features that support placement in the family. The identification of a fossil pupa as Bunaeini (Saturniidae) is well supported. The other fossils that we evaluate lack definitive bombycoid and, in several cases, even lepidopteran characters. Some of these dubious fossils have been used as calibration points in earlier studies casting doubt on the resulting age estimates. All fossil specimens reliably assigned to Bombycoidea are relatively young, the earliest fossil evidence of the superfamily dating to the middle Miocene.
Correlation Analysis on Anatomical Variants of Accessory Foramina in the Sphenoid Bone for Oncological Surgery

Simple Summary Anatomical variants are traits that differ between individuals. The sphenoid bone has numerous variant features, such as foramina and canals, that may be involved in surgical procedures. This study on CT-scan images describes the foramen meningo-orbitale, the foramen of Vesalius, the canaliculus innominatus and the palatovaginal canal and their relationships. For the first time, a correlation between the foramen of Vesalius and the canaliculus innominatus was found. This topic is especially important in cranial base surgical procedures that may involve tumor treatment. Abstract The sphenoid bone presents several anatomical variations, including accessory foramina, such as the foramen meningo-orbitale, the foramen of Vesalius, the canaliculus innominatus and the palatovaginal canal, which may be involved in tumor invasion or surgery of surrounding structures. Therefore, clinicians and surgeons have to consider these variants when planning surgical interventions of the cranial base. The prevalence of each variant is reported in the published literature, but very little information is available on the possible correlation among different variants. Here, 300 CT scans of patients (equally divided among males and females) were retrospectively assessed to investigate the presence of the foramen meningo-orbitale, the foramen of Vesalius, the canaliculus innominatus and the palatovaginal canal. Possible differences in the prevalence of each accessory foramen according to sex were assessed, as well as possible correlations among different variants through the Chi-square test (p < 0.01). Overall, the prevalence of the foramen meningo-orbitale, the foramen of Vesalius, the canaliculus innominatus and the palatovaginal canal was 30.7%, 67.7%, 14.0% and 35.3%, respectively, without any difference according to sex (p > 0.01). A significant positive correlation was found between the foramen of Vesalius and canaliculus innominatus, both in males and in females (p < 0.01). In detail, subjects with canaliculus innominatus in 85.7–100.0% of cases also showed the foramen of Vesalius, independently from sex and side. The present study provided novel data about the prevalence of four accessory foramina of the sphenoid bone in an Italian population, and a correlation between the foramen of Vesalius and the canaliculus innominatus was found for the first time. As these accessory foramina host neurovascular structures, the results of this study are thus useful for appropriate planning surgical procedures that are tailored to the anatomical configuration of the patient and for improving techniques to avoid accidental injuries in cranial base surgery. Knowledge of the topography, frequencies and the presence/absence of these additional foramina are pivotal for a successful procedure. Clinicians and surgeons may benefit from these novel data for appropriate recognition of the variants, decision-making, pre-operative and treatment planning, improvement of the procedures, screening of patients and prevention of misdiagnosis.
Functional connectivity alterations in the frontoparietal network and sensorimotor network are associated with behavioral heterogeneity in blepharospasm

Objective Primary blepharospasm (BSP) is a clinically heterogeneous disease that manifests not only as spasmodic closure of the eyelids but also sometimes with apraxia of eyelid opening (AEO). This cross-sectional study aimed to investigate differences in the neural mechanisms of isolated BSP and BSP-associated AEO subtypes, which may reveal the pathophysiology underlying different phenotypes. Methods A total of 29 patients manifested as isolated BSP, 17 patients manifested as BSP associated with AEO, and 28 healthy controls underwent resting-state functional near-infrared spectroscopy (fNIRS). We assessed functional connectivity (FC) between regions of interest (ROIs) in the fronto-parietal control network (PFCN) and sensorimotor network (SMN). We also examined the relationship between altered FC and behavioral data. Results In the FPCN, ROI- analyses showed decreased FC between the left premotor cortex and supramarginal gyrus in the BSP with AEO group compared to the isolated BSP group. In the SMN, both subgroups showed hypoconnectivity of the left premotor cortex with the right primary motor cortex, primary sensory cortex, and somatosensory association cortex. This hypoconnectivity was positively correlated with the total number of botulinum toxin A treatments, which suggests that long-term botulinum toxin A treatment may modulate motor sequence planning and coordination. Conclusion These findings showed different connectivity alterations in neural networks associated with motor and cognitive control among different behavioral phenotypes of BSP. The identification of specific alterations in various networks that correspond to clinical heterogeneity may inform the identification of potential biomarkers for early diagnosis and personalized neuromodulation targets for treating different BSP subphenotypes.
Incidence and Factors Related to Prolonged Postoperative Cognitive Decline (POCD) in Elderly Patients Following Surgery and Anaesthesia: A Systematic Review

Aim The aim of this systematic review is to explore the current literature to provide evidence regarding the incidence and risk factors of prolonged POCD in elderly patients following cardiac and non-cardiac surgical interventions. Methods The PubMed and Google Scholar databases were searched using appropriate keywords and search engines for adequate evidence from studies meeting the inclusion criteria so as to reveal the end-point, which was the presence of prolonged POCD in elderly patients following surgery and anaesthesia. The incidence of POCD at different time intervals and the variables predicting the occurrence of POCD were analysed. Results The results of 23 articles covering 5077 patients (3694 non cardiac and 1383 cardiac surgeries) were carefully analysed. POCD occurs from the first postoperative day and lasts for potentially long periods. The incidence of POCD in this review ranged from 2.2% to 35.7%. More specifically, it ranged from 2.2% to 31.5% in non-cardiac surgeries and 11.8% to 35.7% in patients who had undergone cardiac surgeries. Some of the independent risk factors (predictors) for the development of POCD were advanced age, high concentration of neuroinflammatory mediators detectable in plasma, low SpO2, longer anaesthetic and surgical duration, and depth of anaesthesia. Conclusion This review can only provide limited evidence of prolonged POCD (more than a year) and further research that involves better study designs, larger samples, involving longer follow-up, and at different sites (multicentre) is highly advised. This in turn may help researchers and clinicians to discover the actual causes and risk factors and develop appropriate preventive and treatment protocols to tackle POCD in the ageing surgical population.
Soil Moisture Retrieval over a Semiarid Area by Means of PCA Dimensionality Reduction

Abstract The main objective of this study is to develop a multifeature soil moisture retrieval method based on the principal component analysis (PCA) dimensionality reduction technique. RADARSAT-2 data were used to compute the backscattering coefficients and polarimetric variables. The optimal input features for soil moisture retrieval were selected by means of PCA dimensionality reduction and least root mean square error (RMSE) criterion. The support vector regression (SVR) model was used to estimate soil moisture content. The results indicated that the optimal features extracted by the PCA dimensionality reduction showed high correlation with soil moisture content. The RMSE, R2 (determination coefficient) and mean relative error (MRE) were (1.4 vol.%, 0.73, 18.2%) and (1.6 vol.%, 0.66, 15.6%) over the low grass cover areas A and B, respectively. For the bare soil areas A and B, the statistic results were (1.3 vol.%, 0.76, 12.1%) and (1.6 vol.%, 0.72, 14.9%), respectively. This case study confirmed the potential of the developed approach to estimate soil moisture over the low grass cover and bare soil areas.
Mepolizumab has clinical benefits including oral corticosteroid sparing irrespective of baseline EGPA characteristics

Background The Mepolizumab in Relapsing or Refractory EGPA (MIRRA) trial (GSK ID: 115921/NCT02020889) demonstrated that mepolizumab increased remission time and reduced oral corticosteroid (OCS) use compared with placebo in patients with relapsing or refractory eosinophilic granulomatosis with polyangiitis (EGPA). The present analysis investigated the impact of baseline characteristics on clinical outcomes and characterised the OCS-sparing effect of mepolizumab. Methods In a phase 3, randomised controlled trial for patients with EGPA (MIRRA), patients received standard of care plus mepolizumab 300 mg or placebo every 4 weeks for 52 weeks. The accrued duration of remission, the proportion of patients in remission at weeks 36 and 48, and the proportion of patients with clinical benefit (remission, OCS or relapse-related) were assessed according to baseline EGPA characteristic subgroups (post hoc). Mepolizumab-related OCS-sparing benefits were also quantified. Results Accrued duration of remission and the proportion of patients in remission at weeks 36 and 48 were greater with mepolizumab than placebo across the baseline subgroups of refractory disease, immunosuppressant use, EGPA duration, relapse number and OCS use ≤20 mg·day−1. The proportion of patients with clinical benefit was greater with mepolizumab versus placebo (range 76–81% versus 25–39%), irrespective of immunosuppressant use or EGPA duration. Patients treated with mepolizumab versus placebo accrued significantly more weeks on OCS ≤4 mg·day−1 (OR 5.06, 95% CI 2.47–10.38) and had a mean of 1423.1 mg less per-patient OCS exposure over 52 weeks. Conclusions Mepolizumab treatment provided benefits to patients with EGPA across varying baseline clinical characteristics and can be considered an OCS-sparing treatment in EGPA.
Gender Stratification and Changing in Gender Expectations: A comparative analysis between coeducational schools and single-sex schools in Erbil

This study explores the impact of coeducational schools on reducing gender inequality by comparing students' perspectives in coeducational and single-sex schools with similar academic levels. Seventh-grade (aged 12,13) and twelfth-grade (aged 17,18) students from three basic and three preparatory schools participate. Qualitative data is gathered through eight focused group interviews with 80 students and analyzed using coding. Quantitative data is collected through questionnaires, including students' perspectives on gender issues and controllable variables related to their home background. SPSS program is used for analysis, employing cross-tabulation and correlation. The study supports the "enlightenment approach" as both types of schools show changes in gender expectations, with twelfth-grade students exhibiting more egalitarian views. Gender inequality in teacher treatment was observed in all selected schools. Preparatory coeducational schools showed better treatment towards girls, while twelfth-grade girls faced inequality in a preparatory single-sex school for girls. Similarly, a significant gender inequality was found in teacher treatment towards boy students in the preparatory school for boys. This indicates that the school somewhat reproduces inequality. In analyzing the questionnaire, gender, age, and school type were compared as independent variables with dependent variables related to students' perspectives. Results showed that girls generally hold more egalitarian perspectives than males, older students are more egalitarian than younger students, and students in coeducational schools are more egalitarian than those in single-sex schools. This suggests that coeducation is a step towards gender equality. Furthermore, a comparison between seventh-grade and twelfth-grade students' perspectives in each selected school revealed changes in gender expectations between these two stages, emphasizing the impact of education on enlightening gender equality. However, when comparing students' perspectives with their home background, the impact of the school becomes less apparent. Despite the influence of school or education on gender expectations, home socialization remains the primary factor in increasing or reducing gender inequality.
A Scoring System to Determine the Risk Factors Causing Recurrent Pulmonary Thromboembolism

Background: The risk of recurrence in pulmonary embolism is the highest in the first week after the acute event. Although it decreases over time, it may remain high for months depending on compliance with treatment and the nature of the underlying risk factor. Our study aimed to identify risk factors that lead to recurrence in pulmonary thromboembolism (PTE) patients and establish an easy-to-use scoring system that determines the risk of recurrence after the first embolism. Methods: We retrospectively evaluated 1452 patients who were diagnosed with acute PTE between 7/1/2014 and 7/1/2019. Demographic data, comorbidities and clinical data of the patients, and risk factors were recorded. The relationship of the examined parameters with recurrent PTE was evaluated. Results: Diabetes mellitus (DM), hypertension, obesity, and the presence of at least one hereditary risk factor were found to be associated with recurrence. The sensitivity of our score was 66.9%, the specificity was 63.2%, the positive predictive value was 19%, and the negative predictive value was 93.7%. The risk of recurrence in the patients identified as high-risk in the scoring system was 3.47 times higher than those identified as low-risk. Conclusion: In terms of risk of recurrence, special attention should be paid to patients with diabetes, HT, obesity and any of the hereditary risk factors. Using scoring systems to determine the risk of recurrence will be valuable and interesting as it is easy-to-use, gives quick results and provides quantitative results.