Miracle-dz/UniFAR-FTUs huggingface dataset:
Claims data analyses unable to properly characterize the value of neurologists in epilepsy care

Objective To determine the association of a neurologist visit with health care use and cost outcomes for patients with incident epilepsy. Methods Using health care claims data for individuals insured by United Healthcare from 2001 to 2016, we identified patients with incident epilepsy. The population was defined by an epilepsy/convulsion diagnosis code (ICD codes 345.xx/780.3x, G40.xx/R56.xx), an antiepileptic prescription filled within the succeeding 2 years, and neither criterion met in the 2 preceding years. Cases were defined as patients who had a neurologist encounter for epilepsy within 1 year after an incident diagnosis; a control cohort was constructed with propensity score matching. Primary outcomes were emergency room (ER) visits and hospitalizations for epilepsy. Secondary outcomes included measures of cost (epilepsy related, not epilepsy related, and antiepileptic drugs) and care escalation (including EEG evaluation and epilepsy surgery). Results After participant identification and propensity score matching, there were 3,400 cases and 3,400 controls. Epilepsy-related ER visits were more likely for cases than controls (year 1: 5.9% vs 2.3%, p < 0.001), as were hospitalizations (year 1: 2.1% vs 0.7%, p < 0.001). Total medical costs for epilepsy care, nonepilepsy care, and antiepileptic drugs were greater for cases (p ≤ 0.001). EEG evaluation and epilepsy surgery occurred more commonly for cases (p ≤ 0.001). Conclusions Patients with epilepsy who visited a neurologist had greater subsequent health care use, medical costs, and care escalation than controls. This comparison using administrative claims is plausibly confounded by case disease severity, as suggested by higher nonepilepsy care costs. Linking patient-centered outcomes to claims data may provide the clinical resolution to assess care value within a heterogeneous population.
Fitness traits of deoxynivalenol and nivalenol-producing Fusarium graminearum species complex strains from wheat

Fusarium graminearum of the 15-acetyl(A)deoxynivalenol(D0N) chemotype is the main cause of Fusarium head blight (FHB) of wheat in south of Brazil. However, 3-ADON and nivalenol(NIV) chemotypes have been found in other members of the species complex causing FHB in wheat. To improve our understanding of the pathogen ecology, we assessed a range of fitness-related traits in a sample of 30 strains representatives of 15-ADON (F. graminearum), 3-ADON (F. cortaderiae and F. austroamericanum) and NIV (F. meridionale and F. cortaderiae). These included: perithecia formation on three cereal-based substrates, mycelial growth at two suboptimal temperatures, sporulation and germination, pathogenicity towards a susceptible and a moderately resistant cultivar and sensitivity to tebuconazole. The most important trait favoring F. graminearum was its 2x higher sexual fertility (> 40% PPI = perithecia production index) than the other species (< 30% PPI); PPI varied among substrates (maize > rice > wheat). In addition, sensitivity to tebuconazole appeared lower in F. graminearum which had the only strain with EC50 > 1 ppm. In the pathogenicity assays, the DON-producers were generally more aggressive (1.5 to 2x higher final severity) towards the two cultivars, with 3-ADON or 15-ADON leading to higher area under the severity curve than the NIV strains in the susceptible and moderately resistant cv. , respectively. There was significant variation among strains of a same species with regards asexual fertility (mycelial growth, macroconidia production and germination), which suggest a strain-rather than a species-specific differences. These results contribute new knowledge to improve our understanding of the pathogen-related traits that may explain the dominance of certain members of the species complex in specific wheat agroecosystems.
Systemic, but not local, low-grade endotoxinemia increases plasma sCD163 independently of the cortisol response

Aims/hypothesis The macrophage-specific glycoprotein sCD163 has emerged as a biomarker of low-grade inflammation in the metabolic syndrome and related disorders. High sCD163 levels are seen in acute sepsis as a result of direct lipopolysaccharide-mediated shedding of the protein from macrophage surfaces including Kupffer cells. The aim of this study was to investigate if low-grade endotoxinemia in human subjects results in increasing levels of sCD163 in a cortisol-dependent manner. Methods We studied eight male hypopituitary patients and eight age- and gender-matched healthy controls during intravenous low-dose LPS or placebo infusion administered continuously over 360 min. Furthermore, we studied eight healthy volunteers with bilateral femoral vein and artery catheters during a 360-min infusion with saline and low-dose LPS in each leg respectively. Results: Systemic low-grade endotoxinemia resulted in a gradual increase in sCD163 from 1.65 ± 0.51 mg/L (placebo) to 1.92 ± 0.46 mg/L (LPS) at 220 min, P = 0.005 and from 1.66 ± 0.42 mg/L (placebo) to 2.19 ± 0.56 mg/L (LPS) at 340 min, P = 0.006. A very similar response was observed in hypopituitary patients: from 1.59 ± 0.53 mg/L (placebo) to 1.83 ± 0.45 mg/L (LPS) at 220 min, P = 0.021 and from 1.52 ± 0.53 mg/L (placebo) to 2.03 ± 0.44 mg/L (LPS) at 340 min, P < 0.001. As opposed to systemic treatment, continuous femoral artery infusion did not result in increased sCD163. Conclusion: Systemic low-grade endotoxinemia resulted in increased sCD163 to levels seen in the metabolic syndrome in both controls and hypopituitary patients. This suggests a direct and cortisol-independent effect of LPS on the shedding of sCD163. We observed no effect of local endotoxinemia on levels of serum sCD163.
Olfactory Dysfunction in Aging African American and Caucasian Men With HIV: A Pilot Study

Abstract As people age with HIV, olfactory dysfunctions may become more pronounced, especially for African Americans who are predisposed to declines in olfaction. In this cross-sectional study, 34 middle-age and older African American and 17 Caucasian men living with HIV were administered two objective olfactory measures (UPSIT). In the Smell Threshold Test, compared to the HIV-negative age norms, adults living with HIV were significantly less able to detect a lower threshold smell. In the University of Pennsylvania Smell Identification Test, compared to the HIV-negative age norms, adults living with HIV were significantly less able to correctly identify odors; furthermore, using such norms, African Americans with HIV were less likely to correctly identify odors compared to Caucasians with HIV. Since the literature indicates that African Americans have a stronger attraction for salty and sweet foods, such olfactory dysfunction may contribute to poor eating habits, potentially predisposing this population to additional health problems.
Vacuolar proton-translocating ATPase is required for antifungal resistance and virulence of Candida glabrata

Vacuolar proton-translocating ATPase (V-ATPase) is located in fungal vacuolar membranes. It is involved in multiple cellular processes, including the maintenance of intracellular ion homeostasis by maintaining acidic pH within the cell. The importance of V-ATPase in virulence has been demonstrated in several pathogenic fungi, including Candida albicans. However, it remains to be determined in the clinically important fungal pathogen Candida glabrata. Increasing multidrug resistance of C. glabrata is becoming a critical issue in the clinical setting. In the current study, we demonstrated that the plecomacrolide V-ATPase inhibitor bafilomycin B1 exerts a synergistic effect with azole antifungal agents, including fluconazole and voriconazole, against a C. glabrata wild-type strain. Furthermore, the deletion of the VPH2 gene encoding an assembly factor of V-ATPase was sufficient to interfere with V-ATPase function in C. glabrata, resulting in impaired pH homeostasis in the vacuole and increased sensitivity to a variety of environmental stresses, such as alkaline conditions (pH 7.4), ion stress (Na+, Ca2+, Mn2+, and Zn2+ stress), exposure to the calcineurin inhibitor FK506 and antifungal agents (azoles and amphotericin B), and iron limitation. In addition, virulence of C. glabrata Δvph2 mutant in a mouse model of disseminated candidiasis was reduced in comparison with that of the wild-type and VPH2-reconstituted strains. These findings support the notion that V-ATPase is a potential attractive target for the development of effective antifungal strategies.
External Cueing Influences Drop Jump Performance in Trained Young Soccer Players

Abstract Oliver, JL, Barillas, SR, Lloyd, RS, Moore, I, and Pedley, J. External cueing influences drop jump performance in trained young soccer players. J Strength Cond Res 35(6): 1700–1706, 2021—Drop jump (DJ) characteristics provide insight on power production and injury risk. The purpose of this study was to investigate the effect of external cueing on DJ characteristics in young male soccer players. Fourteen academy soccer players performed DJs with 4 different conditions, control (CONT), contact cue (CC), height cue (HC), and quiet cue (QC). Performance measures were reactive strength index (RSI), jump height, ground contact time (GCT), and take-off impulse, with injury risk reflected by impact peak, impact timing, and landing impulse. Contact cue showed a very large significant reduction in GCT (effect size [ES] > 2.0, p < 0.05), and moderate to large increase in RSI, landing impulse, and push-off impulse (ES 0.70–1.55, p < 0.05) compared with all other conditions. Contact cue also moderately increased impact peak when compared with HC and QC (ES ≥ 0.78, p < 0.05). Height cue led to a significant increase in jump height that was moderately greater than other external cues (ES ≥ 0.87, p < 0.05), but with only a small nonsignificant increase compared (ES 0.54, p > 0.05) with CONT. The data showed that all cues provided a specific response; CC reduced GCT and increased RSI, HC increased jump height, and QC reduced outcomes associated with injury risk. Height cue may be advantageous for young soccer players with a low training age because it shows a small to moderate increase in jump height without increasing injury risk. Young players may need to be safely progressed to be able to use a CC to facilitate high reactive strength without being exposed to undue injury risk.
Incidence rates of inflammatory bowel disease in patients with psoriasis, psoriatic arthritis and ankylosing spondylitis treated with secukinumab: a retrospective analysis of pooled data from 21 clinical trials

Objectives Here, we present the reported incidence rates of inflammatory bowel disease (IBD) in patients receiving treatment with secukinumab for psoriasis (PsO), psoriatic arthritis (PsA) or ankylosing spondylitis (AS), in a pooled analysis of 21 clinical trials. Methods Data from all patients who had received at least one dose of secukinumab were included. Safety analyses were conducted to evaluate cumulative IBD rates as well as per-year rates, by indication. Crohn’s disease (CD), ulcerative colitis (UC) and IBD unclassified (IBDU) events were analysed using exposure-adjusted incidence rates (patient incidence rates per 100 patient-years (PY)). Results A total of 7355 patients with a cumulative exposure of 16 226.9 PY were included in the pooled analysis. Among 5181 patients with PsO, there were 14 cases of UC, 5 cases of CD and 1 case of IBDU, with exposure adjusted incidence rates (EAIRs) of 0.13, 0.05 and 0.01, respectively. Of these 20 cases, 14 were new-onset. In 1380 patients with PsA, there were 3 cases of UC, 3 cases of CD and 2 cases of IBDU (EAIRs 0.08, 0.08 and 0.05); 7 of these represented new-onset cases. Among 794 patients with AS, there were 4 cases of UC, 8 cases of CD and 1 case of IBDU (EAIRs 0.2, 0.4 and 0.1); 9 were new-onset cases. In the per year analysis, the EAIRs for each indication did not increase over time with secukinumab treatment. Conclusions In this pooled secukinumab safety analysis of 7355 patients across 21 clinical trials, cases of IBD events (including CD, UC and IBDU) were uncommon.
Exercise stress test in apparently healthy individuals − where to place the finish line? The Ferrari corporate wellness programme experience

Aims The aim of our study was to assess the clinical significance of the exercise stress testing endpoints, namely 85% of maximal theoretical heart rate (MTHR), metabolic equivalent of task, and rating of perceived exertion (RPE), and their relation to electrocardiographic (ECG) changes in a healthy adult population. Methods A cross-sectional study was conducted on 408 males and 52 females (mean age 39.4 ± 8.6 years) who performed the maximal cycle ergometer exercise stress test until volitional exhaustion, reporting the RPE score at 85% of MTHR and at peak exercise. Metabolic equivalents of task were indirectly calculated from the maximum workload and compared with the predicted values. Sitting torso-lead ECG and blood pressure were recorded at rest, during exercise and during recovery. Results Of 460 participants, 73% exceeded 85% of MTHR. The RPE score represented the overall most significant endpoint of exercise stress testing, with the median value of 17 at peak exercise. ECG events were detected in 23/124 (18.5%) who reached ≤ 85% of MTHR and in 61/336 (18.2%) who achieved >85% of MTHR (p = 0.92). In the latter group, 54% of ECG changes occurred at < 85% of MTHR and 46% at > 85% of MTHR (p = 0.51). If the exercise stress testing had been interrupted at ≤ 85% of MTHR, almost half of the ECG events would have remained undetected and 35% of the cardiovascular abnormalities observed at the diagnostic follow-up would have remained undiagnosed. Conclusion Terminating exercise stress testing before volitional exhaustion and an RPE score of 17 limits the test accuracy and reduces the possibility to detect cardiovascular abnormalities in apparently healthy adult populations.
Numerical simulation of the structural behaviour of single, multi-arch and open-spandrel arch masonry bridges

Les auteurs deposent l'application d'un modele numerique specifiquement developpe pour l'analyse des constructions de maconnerie, plus particulierement pour simuler la reponse en service des ponts-arc en maconnerie a tympans ajoures. Le modele a permis de prendre en compte la plupart des phenomenes impliques sans la capacite de resistance de la structure: fissuration en traction, plastification et ecrasement a la compression et equilibre de second ordre. Pour illustrer la capacite du modele, deux exemples d'application sont presentes. Le premier, une experimentation sur modele experimental reduit, a permis de valider le modele numerique pour l'analyse des ponts en arc a tympans ajoures, malgre quelques difficultes qui seront discutees. Le second exemple est le pont Adolphe au Luxembourg, etudie par Paul Sejourne, qui a l'arc en maconnerie le plus long d'Europe.
The Presence of a Transporter-Induced Protein Binding Shift: A New Explanation for Protein-Facilitated Uptake and Improvement for In Vitro-In Vivo Extrapolation

Accurately predicting hepatic clearance is an integral part of the drug-development process, and yet current in vitro to in vivo (IVIVE) extrapolation methods yield poor predictions, particularly for highly protein-bound transporter substrates. Explanations for error include inaccuracies in protein-binding measurements and the lack of recognition of protein-facilitated uptake, where both unbound and bound drug may be cleared, violating the principles of the widely accepted free drug theory. A new explanation for protein-facilitated uptake is proposed here, called a transporter-induced protein binding shift. High-affinity binding to cell-membrane proteins may change the equilibrium of the nonspecific binding between drugs and plasma proteins, leading to greater cellular uptake and clearance than currently predicted. The uptake of two lower protein-binding organic anion transporting polypeptide substrates (pravastatin and rosuvastatin) and two higher binding substrates (atorvastatin and pitavastatin) were measured in rat hepatocytes in incubations with protein-free buffer versus 100% plasma. Decreased unbound Km values and increased intrinsic clearance values were seen in the plasma incubations for the highly bound compounds, supporting the new hypothesis and mitigating the IVIVE underprediction previously seen for highly bound transporter substrates.
Early-Life Home Environment and Obesity in a Mexican American Birth Cohort: The CHAMACOS Study

Objective Little is known about the impact of the home environment on biomarkers of obesity, such as adipokines, in children. In this study, we examined the relationship of maternal depressive symptoms and potentially protective social factors, including maternal support and the home learning environment, with body mass index and adipokines. Methods Data were obtained from 326 Mexican American participants from the Center for the Health Assessment of Mothers and Children of Salinas cohort. Plasma adipokine levels were assessed in 326 children by enzyme-linked immunoassay at birth or ages 5, 9, or 14 years. Maternal depressive symptoms were evaluated using the Center for Epidemiological Studies Depression Scale when children were 1, 3.5, 7, and 9 years old; social support was assessed by the Duke-University of North Carolina Questionnaire at ages 1 and 5 years; and home learning environment by the Home Observation for the Measurement of the Environment (HOME) at ages of 6 months and 1, 2, 3.5, 7, 9, and 10.5 years. Results Age was significantly associated with adiponectin (B = −5.0, SE = 0.2) and leptin (B = 0.01, SE = 0.003) levels. Individual time point analyses identified significant positive associations of HOME scores in childhood with adiponectin at ages 9 years (HOME score; age 3.5 years: B = 0.9, p = .04) and 14 years (HOME score; age 7 years: B = 0.6, p = .02, age 9 years: B = 0.6, p = .05, age 10.5 years: B = 0.5, p = .04). We observed significant relationships of maternal depressive symptoms at age 9 years with adiponectin and body mass index z-score at age 14 years (B = −0.2, p = .003 and B = 0.02, p = .002, resp.), which were confirmed in longitudinal models. Conclusions This study adds new evidence that adverse and protective aspects of the home environment could lead to altered obesity status in children.
Photo- and Sono-Dynamic Therapy: A Review of Mechanisms and Considerations for Pharmacological Agents Used in Therapy Incorporating Light and Sound.

As irreplaceable energy sources of minimally invasive treatment, light and sound have, separately, laid solid foundations in their clinic applications. Constrained by the relatively shallow penetration depth of light, photodynamic therapy (PDT) typically involves involves superficial targets such as shallow seated skin conditions, head and neck cancers, eye disorders, early-stage cancer of esophagus, etc. For ultrasound-driven sonodynamic therapy (SDT), however, to various organs is facilitated by the superior. transmission and focusing ability of ultrasound in biological tissues, enabling multiple therapeutic applications including treating glioma, breast cancer, hematologic tumor and opening blood-brain-barrier (BBB). Considering the emergence of theranostics and precision therapy, these two classic energy sources and corresponding sensitizers are worth reevaluating. In this review, three typical therapies using light and sound as a trigger, PDT, SDT, and combined PDT and SDT are introduced. The therapeutic dynamics and current designs of pharmacological sensitizers involved in these therapies are presented. By introducing both the history of the field and the most up-to-date design strategies, this review provides a systemic summary on the development of PDT and SDT and fosters inspiration for researchers working on 'multi-modal' therapies involving light and sound.
Viral population analysis of the taiga tick, Ixodes persulcatus, by using Batch Learning Self-Organizing Maps and BLAST search

Ticks transmit a wide range of viral, bacterial, and protozoal pathogens, which are often zoonotic. Several novel tick-borne viral pathogens have been reported during the past few years. The aim of this study was to investigate a diversity of tick viral populations, which may contain as-yet unidentified viruses, using a combination of high throughput pyrosequencing and Batch Learning Self-Organizing Map (BLSOM) program, which enables phylogenetic estimation based on the similarity of oligonucleotide frequencies. DNA/cDNA prepared from virus-enriched fractions obtained from Ixodes persulcatus ticks was pyrosequenced. After de novo assembly, contigs were cataloged by the BLSOM program. In total 41 different viral families and order including those previously associated with human and animal diseases such as Bunyavirales, Flaviviridae, and Reoviridae, were detected. Therefore, our strategy is applicable for viral population analysis of other arthropods of medical and veterinary importance, such as mosquitos and lice. The results lead to the contribution to the prediction of emerging tick-borne viral diseases. A sufficient understanding of tick viral populations will also empower to analyze and understand tick biology including vector competency and interactions with other pathogens.
Outbreaks of canine distemper in Dutch and Belgian mink farms

Abstract Background: Vaccination of farmed minks against canine distemper virus (CDV) has proved to be very effective. In the Netherlands, vaccination of farmed minks against CDV was mandatory until the closure of the local agricultural product boards at the end of 2014. Objectives: To describe the first documented outbreaks of CD in Dutch mink farms since the closure of the agricultural product boards, as well as an outbreak in Belgium, with special attention to genotyping of the isolates. Methods: A full post-mortem was performed on three carcasses per submission from farms A–C and on two carcasses from farm D. Molecular detection with subsequent typing was performed on eleven samples originating from four different farms. To assess genetic diversity partial sequences of the H gene of CDV were compared based on phylogenetic analysis. Results: In 2017, there was a sudden series of CD outbreaks affecting four mink farms in the Netherlands (A–C) and Belgium (D). Gross, histologic and immunohistochemical findings were similar. There was a degree of genetic similarity between the viruses on farms A and D (98.5%) and between the viruses on farms B and C (97.3%), but the viruses from farms A and D belonged to a different clade than the viruses from farms B and C. Higher mortalities were reported in white and pastel minks. Conclusions: Findings indicated that the difference in severity of the outbreaks was partially related to the genetic composition of the farm populations. Vaccination against CDV on Dutch and Belgian mink farms seems warranted.