Miracle-dz/UniFAR-FTUs huggingface dataset:
Imbalance of Drug Transporter-CYP450s Interplay by Diabetes and Its Clinical Significance

The pharmacokinetics of a drug is dependent upon the coordinate work of influx transporters, enzymes and efflux transporters (i.e., transporter-enzyme interplay). The transporter–enzyme interplay may occur in liver, kidney and intestine. The influx transporters involving drug transport are organic anion transporting polypeptides (OATPs), peptide transporters (PepTs), organic anion transporters (OATs), monocarboxylate transporters (MCTs) and organic cation transporters (OCTs). The efflux transporters are P-glycoprotein (P-gp), multidrug/toxin extrusions (MATEs), multidrug resistance-associated proteins (MRPs) and breast cancer resistance protein (BCRP). The enzymes related to drug metabolism are mainly cytochrome P450 enzymes (CYP450s) and UDP-glucuronosyltransferases (UGTs). Accumulating evidence has demonstrated that diabetes alters the expression and functions of CYP450s and transporters in a different manner, disordering the transporter–enzyme interplay, in turn affecting the pharmacokinetics of some drugs. We aimed to focus on (1) the imbalance of transporter-CYP450 interplay in the liver, intestine and kidney due to altered expressions of influx transporters (OATPs, OCTs, OATs, PepTs and MCT6), efflux transporters (P-gp, BCRP and MRP2) and CYP450s (CYP3As, CYP1A2, CYP2E1 and CYP2Cs) under diabetic status; (2) the net contributions of these alterations in the expression and functions of transporters and CYP450s to drug disposition, therapeutic efficacy and drug toxicity; (3) application of a physiologically-based pharmacokinetic model in transporter–enzyme interplay.
Integrated, Real-Time Digital Measurement during Ureteroscopic Procedures for Nephrolithiasis: A Workflow Feasibility Study.

INTRODUCTION Accurate estimation of stone fragment size during ureteroscopic lithotripsy procedures facilitates operative efficiency and predicts the safety of fragment extraction or spontaneous passage. Using a novel stone measurement software application, this study assesses the feasibility of performing integrated, real-time digital stone measurement during ureteroscopy. METHODS This workflow feasibility study was conducted in two phases. First, in the ex vivo simulation, mock stone fragments were placed in a renal collecting system training model. A basket extraction task was performed using a digital ureteroscope, with and without digital stone measurement. The time required to perform the tasks was recorded and compared. Second, in the in vivo workflow trial, adult patients undergoing ureteroscopic stone procedures were prospectively enrolled. Intraoperative measurements of stone fragments were performed to determine the time required to complete the measurements. Technical failures and perioperative complications were recorded. RESULTS In the ex vivo simulation, 20 mock stones mimicking varied fragmentation conditions were tested in the training model. The mean completion time of the basketing task without versus with digital stone measurement was 16.5 seconds (range 10.2-33.7) versus 38.9 seconds (range 27.2-60.0). Mean additional time required to measure stones was 22.3 seconds (range 8.4-42.7). In the in vivo workflow trial, 9 patients undergoing ureteroscopy were enrolled. A median of 5 fragments (range 3-10) were measured in each patient. Mean completion time for each measurement was 10.1 seconds (range 8.2-12.8). Mean total time required to perform digital measurement per procedure was 50.8 seconds (range 25.9-99.0). No technical failures or clinical complications were observed. CONCLUSIONS Integrating real-time digital stone measurement during ureteroscopy is safe and feasible. The findings support clinical trials of digital stone measurement to enhance intraoperative decision-making during ureteroscopy.
Automated Pulse Oximeter Waveform Analysis to Track Changes in Blood Pressure During Anesthesia Induction: A Proof-of-Concept Study

BACKGROUND: Intraoperative hypotension is associated with postoperative complications and death. Oscillometric brachial cuffs are used to measure arterial pressure (AP) in most surgical patients but may miss acute changes in AP. We hypothesized that pulse oximeter waveform analysis may help to detect changes in systolic AP (SAP) and mean AP (MAP) during anesthesia induction. METHODS: In 40 patients scheduled for an elective surgery necessitating general anesthesia and invasive AP monitoring, we assessed the performance of a pulse oximeter waveform analysis algorithm (optical blood pressure monitoring [oBPM]) to estimate SAP, MAP, and their changes during the induction of general anesthesia. Acute AP changes (>20%) in SAP and MAP assessed by the reference invasive method and by oBPM were compared using 4-quadrant and polar plots. The tracking ability of the algorithm was evaluated on changes occurring over increasingly larger time spans, from 30 seconds up to 5 minutes. The second objective of the study was to assess the ability of the oBPM algorithm to cope with the Association for the Advancement of Medical Instrumentation (AAMI) standards. The accuracy and precision of oBPM in estimating absolute SAP and MAP values compared to the invasive method was evaluated at various instants after algorithm calibration, from 30 seconds to 5 minutes. RESULTS: Rapid changes (occurring over time spans of ≤60 seconds) in SAP and MAP assessed by oBPM were strongly correlated and showed excellent concordance with changes in invasive AP (worst-case Pearson correlation of 0.94 [0.88, 0.97] [95% confidence interval], concordance rate of 100% [100%, 100%], and angular concordance rate at ±30° of 100% [100%, 100%]). The trending ability tended to decrease progressively as the time span over which the changes occurred increased, reaching 0.89 (0.85, 0.91) (Pearson correlation), 97% (95%, 100%) (concordance rate), and 90% (85%, 94%) (angular concordance rate) in the worst case. Regarding accuracy and precision, oBPM-derived SAP values were shown to comply with AAMI criteria up to 2 minutes after calibration, whereas oBPM-derived MAP values were shown to comply with criteria at all times. CONCLUSIONS: Pulse oximeter waveform analysis was useful to track rapid changes in SAP and MAP during anesthesia induction. A good agreement with reference invasive measurements was observed for MAP up to at least 5 minutes after initial calibration. In the future, this method could be used to track changes in AP between intermittent oscillometric measurements and to automatically trigger brachial cuff inflation when a significant change in AP is detected.
The Suppression of Inferences From Counterfactual Conditionals

We examine two competing effects of beliefs on conditional inferences. The suppression effect occurs for conditionals, for example, "if she watered the plants they bloomed," when beliefs about additional background conditions, for example, "if the sun shone they bloomed" decrease the frequency of inferences such as modus tollens (from "the plants did not bloom" to "therefore she did not water them"). In contrast, the counterfactual elevation effect occurs for counterfactual conditionals, for example, "if she had watered the plants they would have bloomed," when beliefs about the known or presupposed facts, "she did not water the plants and they did not bloom" increase the frequency of inferences such as modus tollens. We report six experiments that show that beliefs about additional conditions take precedence over beliefs about presupposed facts for counterfactuals. The modus tollens inference is suppressed for counterfactuals that contain additional conditions (Experiments 1a and 1b). The denial of the antecedent inference (from "she did not water the plants" to "therefore they did not bloom") is suppressed for counterfactuals that contain alternatives (Experiments 2a and 2b). We report a new "switched-suppression" effect for conditionals with negated components, for example, "if she had not watered the plants they would not have bloomed": modus tollens is suppressed by alternatives and denial of the antecedent by additional conditions, rather than vice versa (Experiments 3a and 3b). We discuss the implications of the results for alternative theories of conditional reasoning.
Cytotoxicity and antibacterial activity of scutellarein and carajurone-enriched fraction obtained from the hydroethanolic extract of the leaves of Fridericia chica (Bonpl.) L.G. Lohmann

Abstract The hydroethanolic extract obtained from the dry leaves of Fridericia chica (HEFc) underwent several fractionations by different chromatographic techniques. The ethyl acetate and dichloromethane fraction were subjected to phytochemical analysis, resulting in the identification and isolation of scutellarein (1) and in a fraction rich in carajurone (2). They were tested for cytotoxicity in CHO-K1 and the antibacterial activity and mode of action by in vitro assays. The HEFc and scutellarein (1) presented no cytotoxicity. The results showed good antibacterial effect of HEFc against Streptococcus pyogenes and Staphylococcus aureus and moderate activity for Staphylococcus epidermidis, Pseudomonas aeruginosa and Salmonella typhimurium. The fraction containing the compound carajurone (2) showed good activity against Staphylococcus aureus and Staphylococcus epidermidis and moderate activity against Streptococcus pyogenes. Scutellarein (1) showed no activity against the bacteria tested. HEFc antibacterial mode of action appeared to be associated with changes in the permeability of bacterial membranes and nucleotide leakage. Graphical Abstract
Training and Competition Load in Female Basketball: A Systematic Review

The scientific literature on women’s basketball is still limited, mainly in performance parameters. The purpose of this study was to analyse the state of art on the internal and external loads supported by female basketball players during sports practice. The design of this research is theoretical. The most relevant databases were searched for pertinent published studies according to the following keywords: “basketball”, “female” or “woman”, “training” or “competition”, “load” or “demand”. Of the 644 studies initially identified, 26 were selected for a complete review. These investigations were characterised by having as an objective an individualization of training for this type of population. Of the selected studies, it was evaluated: (i) goal (training, competition or both); (ii) category (stages: U14, U16, U18 and senior; level: state, national or international); (iii) type of load (Internal, External or both); (iv) instruments used and (v) variables analysed. The most studied goal was competition, mainly in senior national level, carrying out an analysis of the external and internal load together. Depending on the instruments and the variables used, the subjective load analysis was recurrent and important in the publication of articles in this topic. The quality of the studies was good, but for a better description of women’s basketball, there is a need to jointly investigate sports training and competition, to study the training categories and to use micro technology that guarantees obtaining objective and reliable data.
Instrumenting Polyodon spathula (Paddlefish) Rostra in Flowing Water with Strain Gages and Accelerometers

The prominent rostrum of the North American Paddlefish, supported by a lattice-like endoskeleton, is highly durable, making it an important candidate for bio-inspiration studies. Energy dissipation and load-bearing capacity of the structure from extreme physical force has been demonstrated superior to that of man-made systems, but response to continuous hydraulic forces is unknown and requires special instrumentation for in vivo testing on a live fish. A single supply strain gage amplifier circuit has been combined with a digital three-axis accelerometer, implemented in a printed circuit board (PCB), and integrated with the commercial-off-the-shelf Adafruit Feather M0 datalogger with a microSD card. The device is battery powered and enclosed in silicon before attachment around the rostrum with a silicon strap "watch band. " As proof-of-concept, we tested the instrumentation on an amputated Paddlefish rostrum in a water-filled swim tunnel and successfully obtained interpretable data. Results indicate that this design could work on live swimming fish in future in vivo experiments.
Advanced machine learning model for better prediction accuracy of soil temperature at different depths

Soil temperature has a vital importance in biological, physical and chemical processes of terrestrial ecosystem and its modeling at different depths is very important for land-atmosphere interactions. The study compares four machine learning techniques, extreme learning machine (ELM), artificial neural networks (ANN), classification and regression trees (CART) and group method of data handling (GMDH) in estimating monthly soil temperatures at four different depths. Various combinations of climatic variables are utilized as input to the developed models. The models’ outcomes are also compared with multi-linear regression based on Nash-Sutcliffe efficiency, root mean square error, and coefficient of determination statistics. ELM is found to be generally performs better than the other four alternatives in estimating soil temperatures. A decrease in performance of the models is observed by an increase in soil depth. It is found that soil temperatures at three depths (5, 10 and 50 cm) could be mapped utilizing only air temperature data as input while solar radiation and wind speed information are also required for estimating soil temperature at the depth of 100 cm.
Gas Phase Protein Folding Triggered by Proton Stripping Generates Inside-Out Structures: A Molecular Dynamics Simulation Study.

The properties of electrosprayed protein ions continue to be enigmatic, owing to the absence of high-resolution structure determination methods in the gas phase. There is considerable evidence that under properly optimized conditions these ions preserve solution-like conformations and interactions. However, it is unlikely that these solution-like conformers represent the "intrinsic" structural preferences of gaseous proteins. In an effort to uncover what such intrinsically preferred conformers might look like, we performed molecular dynamics (MD) simulations of gaseous ubiquitin. Our work was inspired by recent gas phase experiments, where highly extended 13+ ubiquitin ions were transformed to compact 3+ species by proton stripping (Laszlo, K. J.; Munger, E. B.; Bush, M. F. J. Am. Chem. Soc. 2016, 138, 9581-9588). Our simulations covered several microseconds and used a mobile-proton algorithm to account for the fact that H+ in gaseous proteins can migrate between different titratable sites. Proton stripping caused folding of ubiquitin into heterogeneous "inside-out" structures. The hydrophilic core of these conformers was stabilized by charge-charge and polar interactions, while hydrophobic residues were located on the protein surface. Collision cross sections of these MD structures were in good agreement with experimental results. The inside-out structures generated during gas phase folding are in striking contrast to the solution behavior which is dominated by the hydrophobic effect, i.e., the tendency to bury hydrophobic side chains in the core (instead of exposing them to the surface). We do not dispute that native-like proteins can be transferred into the gas phase as kinetically trapped species. However, those metastable conformers do not represent the intrinsic structural preferences of gaseous proteins. Our work for the first time provides detailed insights into the properties of intrinsically preferred gas phase conformers, and we unequivocally find them to have inside-out architectures.
A Rational Use of Clozapine Based on Adverse Drug Reactions, Pharmacokinetics, and Clinical Pharmacopsychology

Using Richardson and Davidson’s model and the sciences of pharmacokinetics and clinical pharmacopsychology, this article reviewed the: (1) poor life expectancy associated with treatment-resistant schizophrenia (TRS), which may be improved in patients who adhere to clozapine; (2) findings that clozapine is the best treatment for TRS (according to efficacy, effectiveness and well-being); and (3) potential for clozapine to cause vulnerabilities, including potentially lethal adverse drug reactions such as agranulocytosis, pneumonia, and myocarditis. Rational use requires: (1) modification of the clozapine package insert worldwide to include lower doses for Asians and to avoid the lethality associated with pneumonia, (2) the use of clozapine levels for personalizing dosing, and (3) the use of slow and personalized titration. This may make clozapine as safe as possible and contribute to increased life expectancy and well-being. In the absence of data on COVID-19 in clozapine patients, clozapine possibly impairs immunological mechanisms and may increase pneumonia risk in infected patients. Psychiatrists should call their clozapine patients and families and explain to them that if the patient develops fever or flu-like symptoms, the psychiatrist should be called and should consider halving the clozapine dose. If the patient is hospitalized with pneumonia, the treating physician needs to assess for symptoms of clozapine intoxication since halving the dose may not be enough for all patients; consider decreasing it to one-third or even stopping it. Once the signs of inflammation and fever have disappeared, the clozapine dose can be slowly increased to the prior dosage level.
The role of peak nasal and oral inspiratory flow in the evaluation of patients with sleep-related breathing disorders.

BACKGROUND Sleep-related breathing disorders (SRBD) are common reported disorders in the adult population. The nose plays an important role in the development of SRBD; thus, the measurement of nasal respiratory function remains an important step in the management of these patients. Peak nasal inspiratory flow (PNIF) is a useful tool to assess nasal airflow and it has recently been studied together with peak oral inspiratory flow (POIF). OBJECTIVE The aim of the present study was to evaluate the role of PNIF and POIF in an adult population of patients affected by SRBD. METHODOLOGY Seventy consecutive adult patients with SRBD were included in the present study. All patients were evaluated with home-based sleep studies (type III), PNIF, POIF, SNOT-22 questionnaire, Epworth Sleepiness Scale test and VAS for nasal obstruction. RESULTS Although PNIF and POIF showed to correlate with each other, no correlations were observed between Apnea Hypopnea index (AHI) and PNIF, POIF or NPI (PNIF/POIF). A further analysis showed a marginal correlation between SNOT- 22 and AHI and between SNOT-22 and POIF. Furthermore, in a multivariate analysis, also POIF marginally correlated with some of the sleep- related SNOT-22 items. CONCLUSIONS In the present study neither PNIF nor POIF were found to be associated with OSAS severity. However, POIF values correlated better than PNIF with sleep related symptoms suggesting that POIF could be a more useful parameter for upper airway assessment in patients with SRBD. In addition, a correlation between OSAS severity, in terms of AHI, and SNOT-22 total score has been reported.
The Long-Term Safety and Quality of Life Effects of Oats in Dermatitis Herpetiformis

The treatment of choice for dermatitis herpetiformis (DH), a cutaneous manifestation of coeliac disease, is a life-long gluten-free diet (GFD). In a GFD, wheat, rye and barley should be strictly avoided, but the role of oats is more controversial. This study aimed to investigate the safety and long-term quality of life and health effects of oat consumption in 312 long-term treated DH patients. Baseline data were gathered from patient records and follow-up data from questionnaires or interviews, and validated questionnaires were used to assess quality of life. We found that altogether 256 patients (82%) were consuming oats as part of their GFD at the follow-up. Long-term follow-up data showed that there were no differences in the presence of long-term illnesses, coeliac disease complications or the usage of medication between those consuming and not consuming oats. However, oat consumers had a better quality of life and reported ongoing gastrointestinal symptoms less frequently (4% vs 19%, p = 0.004) at the follow-up than those not consuming oats. The study established that oats are safe for DH patients and in the long-term seem to improve the quality of life of DH patients.
Immediate or Delayed Transplantation of a Vein Conduit Filled with Nasal Olfactory Stem Cells Improves Locomotion and Axogenesis in Rats after a Peroneal Nerve Loss of Substance

Over the recent years, several methods have been experienced to repair injured peripheral nerves. Among investigated strategies, the use of natural or synthetic conduits was validated for clinical application. In this study, we assessed the therapeutic potential of vein guides, transplanted immediately or two weeks after a peroneal nerve injury and filled with olfactory ecto-mesenchymal stem cells (OEMSC). Rats were randomly allocated to five groups. A3 mm peroneal nerve loss was bridged, acutely or chronically, with a 1 cm long femoral vein and with/without OEMSCs. These four groups were compared to unoperated rats (Control group). OEMSCs were purified from male olfactory mucosae and grafted into female hosts. Three months after surgery, nerve repair was analyzed by measuring locomotor function, mechanical muscle properties, muscle mass, axon number, and myelination. We observed that stem cells significantly (i) increased locomotor recovery, (ii) partially maintained the contractile phenotype of the target muscle, and (iii) augmented the number of growing axons. OEMSCs remained in the nerve and did not migrate in other organs. These results open the way for a phase I/IIa clinical trial based on the autologous engraftment of OEMSCs in patients with a nerve injury, especially those with neglected wounds.
Evaluation of Risk Factors for Falls in Patients with Rheumatoid Arthritis

Background The aim of our study was to investigate the risk factors for falls in the rheumatoid arthritis (RA) patient population in Poland. This would be a major step towards the development of new fall prevention programs. Material/Methods There were 450 RA patients who met the criteria of the American College of Rheumatology who participated in this study. The average age of patient participants was 54.2 years; the average RA duration was 15.1 years. All patients filled out the study questionnaire regarding falls, medications, and diseases, and they filled out the Polish version of the Health Assessment Questionnaire (HAQ). Results Of the 400 patients, 203 patients (51%) experienced falls. Out of the 268 falls experienced by study patients, 113 falls (42%) were due to an environmental cause, the remainder 155 falls were caused by health conditions. The number of falls positively correlated with HAQ scores (r=0.42, P<0.01) and the duration of RA (r=0.39, P<0.05). For individuals who had fallen 3 or more times, there was a stronger positive correlation between the number of falls and the total HAQ score (r=0.61, P<0.01). The main risk factors for falls in the study group were dizziness (odds ratio [OR]=3.42), the use of hypotensive medication (OR=2.82), foot deformities (OR=4.09), and a high HAQ score (OR=2.59). Other factors such as drug use (e.g., glucocorticoids), pain, and duration of RA were measured using a visual analogue scale, and were found not to have increased the risk for falls and fractures (P>0.05). Conclusions Knowledge about risk factors can help identify high-risk patients to help decrease their risk of falling, thus preventing fall-related injuries.