Miracle-dz/UniFAR-FTUs huggingface dataset:
Cumulative health risk assessment of pesticide residues in apple products in the Northwest of Iran using Monte Carlo simulation

Abstract Pesticide residues in fruits and vegetables cause serious health issues, especially among children. This research was carried out to monitor and evaluate the risks of organophosphate pesticide residues in Maragheh County apple products from 2020. The Monte Carlo Simulation approach (MCS) was used to evaluate the non-cancerous effects of exposure to pesticide residues in adults and children. Apple samples were taken every two weeks at the Maragheh central market during the summer and fall months. In this study, seventeen pesticide residues in 30 apple samples were estimated using a modified QuECheRS extraction technique coupled with GC/MS. Of the seventeen organophosphate pesticides, thirteen were identified as pesticide residues (76.47%). The highest concentration found in the apple samples was associated with chlorpyrifos pesticide at 1.05 mg/kg. Pesticide residues exceeding the maximum residue limits (MRLs) were found in 100% of apple specimens, and more than 75% of the samples contained ten or more pesticide residues. Approximately 45%–80% of pesticide residues on apple samples were removed after washing and peeling. Chlorpyrifos pesticide had the highest health quotient (HQ) for men, women, and children with values of 0.046, 0.054, and 0.23, respectively. Cumulative risk assessment (CRA) of non-carcinogenic effects indicates that there is no significant health risk in the adult age group from apple consumption (HI < 1). Nevertheless, children are at high non-cancer risk from eating unwashed apples (HI = 1.3). This finding shows that high levels of pesticide residues in apple samples, especially unwashed apples, can be a serious concern for the health of children. To better protect consumer health, continuous and regular monitoring, strict regulations, training, and awareness of farmers, especially control pre-harvest interval (PHI) is recommended.
Microbial carbon use efficiency in different ecosystems: A meta‐analysis based on a biogeochemical equilibrium model

Soil microbial carbon use efficiency (CUE) is a crucial parameter that can be used to evaluate the partitioning of soil carbon (C) between microbial growth and respiration. However, general patterns of microbial CUE among terrestrial ecosystems (e.g., farmland, grassland, and forest) remain controversial. To address this knowledge gap, data from 41 study sites (n = 197 soil samples) including 58 farmlands, 95 forests, and 44 grasslands were collected and analyzed to estimate microbial CUEs using a biogeochemical equilibrium model. We also evaluated the metabolic limitations of microbial growth using an enzyme vector model and the drivers of CUE across different ecosystems. The CUEs obtained from soils of farmland, forest, and grassland ecosystems were significantly different with means of 0.39, 0.33, and 0.42, respectively, illustrating that grassland soils exhibited higher microbial C sequestration potentials (p < .05). Microbial metabolic limitations were also distinct in these ecosystems, and carbon limitation was dominant exhibiting strong negative effects on CUE. Exoenzyme stoichiometry played a greater role in impacting CUE values than soil elemental stoichiometry within each ecosystem. Specifically, soil exoenzymatic ratios of C:phosphorus (P) acquisition activities (EEAC:P) and the exoenzymatic ratio of C:nitrogen (N) acquisition activities (EEAC:N) imparted strong negative effects on soil microbial CUE in grassland and forest ecosystems, respectively. But in farmland soils, EEAC:P exhibited greater positive effects, showing that resource constraints could regulate microbial resource allocation with discriminating patterns across terrestrial ecosystems. Furthermore, mean annual temperature (MAT) rather than mean annual precipitation (MAP) was a critical climate factor affecting CUE, and soil pH as a major factor remained positive to drive the changes in microbial CUE within ecosystems. This research illustrates a conceptual framework of microbial CUEs in terrestrial ecosystems and provides the theoretical evidence to improve soil microbial C sequestration capacity in response to global change.
Postinjury Alcohol Use Is Associated With Prolonged Recovery After Concussion in NCAA Athletes

Supplemental Digital Content is Available in the Text. Objective: To determine whether alcohol use leads to prolonged clinical recovery or increased severity of concussion symptoms in National Collegiate Athletic Association (NCAA) athletes. Design: Prospective observational study. Setting: Clinical institutions. Participants: Athletes from the NCAA Concussion Assessment Research and Education consortium who sustained a concussion from 2014 to 2021. Interventions: Athletes were divided into 2 groups, those reporting alcohol use postinjury and those reporting no alcohol use postinjury. Main Outcome Measures: Symptom recovery was evaluated as time (in days) from injury to clearance to return to unrestricted play (days until URTP). Severity of concussion symptoms was assessed using the Standardized Sport Concussion Assessment Tool (SCAT3) symptom severity, headache severity, difficulty concentrating, and difficulty remembering scores. These scores were taken a median of 6.6 [interquartile range (IQR) = 4.0-10] and 6 (IQR = 4.0-9.0) days after injury for those who did and did not consume alcohol postinjury respectively and compared with baseline SCAT3 scores. Results: Four hundred eighty four athletes from the data set had complete data for exposure and outcome. The adjusted mean number of days until URTP for athletes reporting alcohol use postinjury [23.3; 95% confidence interval (CI), 20.0-27.2; days] was incidence rate ratio (IRR) 1.32 (95% CI, 1.12-1.55; P < 0.001) times higher than for athletes who reported no alcohol use postinjury [17.7 (95% CI, 16.1-19.3) days]. Postinjury alcohol was not associated with severity of concussion symptoms (P's < 0.05). Conclusion: Self-reported postinjury alcohol use is associated with prolonged recovery but not severity of concussion symptoms in collegiate athletes. This may inform future clinical recommendations regarding alcohol consumption after concussion.
The Effects of Statins on Cognitive Performance Are Mediated by Low-Density Lipoprotein, C-Reactive Protein, and Blood Glucose Concentrations

Abstract Statins are widely used for cardiovascular disease prevention but their effects on cognition remain unclear. Statins reduce cholesterol concentration and have been suggested to provide both beneficial and detrimental effects. Our aim was to investigate the cross-sectional and longitudinal association between statin use and cognitive performance, and whether blood low-density lipoprotein, high-density lipoprotein, triglycerides, glucose, C-reactive protein, and vitamin D biomarkers mediated this association. We used participants from the UK biobank aged 40–69 without neurological and psychiatric disorders (n = 147 502 and n = 24 355, respectively). We performed linear regression to evaluate the association between statin use and cognitive performance and, mediation analysis to quantify the total, direct, indirect effects and the proportion meditated by blood biomarkers. Statin use was associated with lower cognitive performance at baseline (β = −0.40 [−0.53, −0.28], p = <.0001), and this association was mediated by low-density lipoprotein (proportion mediated = 51.4%, p = .002), C-reactive protein (proportion mediated = −11%, p = .006) and blood glucose (proportion mediated = 2.6%, p = .018) concentrations. However, statin use was not associated with cognitive performance, measured 8 years later (β = −0.003 [−0.11, 0.10], p = .96). Our findings suggest that statins are associated with lower short-term cognitive performance by lowering low-density lipoprotein and raising blood glucose concentrations, and better performance by lowering C-reactive protein concentrations. In contrast, statins have no effect on long-term cognition and remain beneficial in reducing cardiovascular risk factors.
Crystal structures of multidrug efflux transporters from Burkholderia pseudomallei suggest details of transport mechanism

Significance We present the crystal structures of the RND drug efflux transporters, BpeB and BpeF from Burkholderia pseudomallei. The molecular mechanism of the RND drug efflux transporters by which the drugs are exported has been described as a recursive three-step functionally rotating mechanism, “access,” “binding,” and “extrusion. ” The BpeB structure could represent an intermediate state that goes back from the extrusion to the access state. We also observed a substrate-binding site. Comparing BpeB/F structures and their homologous structures, we propose a detailed substrate binding and translocation mechanism of the RND transporters. Further understanding of this mechanism could enable the discovery of novel antibiotics with mitigated efflux liabilities and the development of specific inhibitors to combat pathogenic bacteria including Burkholderia.
Medicalising diagnoses and treatment preferences: a retrospective cohort study of throat-related consultations in electronic primary care records.

BACKGROUND Rather than first diagnosing and then deciding on treatment, general practitioners (GP) may intuitively decide on treatment and justify this through choice of diagnosis. AIM To investigate the relationship between choice of a medicalising diagnosis and antibiotic treatment for throat-related consultations. DESIGN & SETTING A retrospective cohort study in a large database of UK electronic primary care records between 1st January 2010 and 1st January 2020. METHOD We included all first throat-related consultations, categorised as either pharyngitis/tonsillitis or sore throat. The outcome was any antibiotic prescription on the consultation date.We estimated GP-level random effects on prescribing and on diagnosis in a series of mixed-effects regression models, including age, sex, weekday, month and clinician characteristics as fixed effects. We grouped GPs into quintiles by antibiotic prescribing propensity and described the proportion of patients they diagnosed pharyngitis/tonsillitis or sore throat in each quintile. RESULTS Our analysis dataset included 393,590 throat-related consultations with 6,881 staff. Diagnosis of pharyngitis/tonsillitis was strongly associated with antibiotic prescribing (adjusted odds ratio 13.41; 95% confidence interval: 12.8-14.04). GP random effect accounted for 18% of variation in prescribing and for 26% of variation in diagnosis. GPs in the lowest quintile of antibiotic prescribing propensity, diagnosed pharyngitis/tonsillitis on 31% of occasions and compared to 55% in the highest. CONCLUSIONS There is substantial between GP variation in diagnosis and treatment of throat-related problems. Preference for a medicalising diagnosis is associated with a preference for antibiotics, suggesting there is a common propensity to both diagnose and treat.
Green synthesis of ZnO-NPs using endophytic fungal extract of Xylaria arbuscula from Blumea axillaris and its biological applications

Abstract The biogenic manufacture of nanoparticles utilising endophytic fungus is an eco-friendly, cost-effective, and secure alternative to constructing chemical methods. The prime focus of the study was to fabricate ZnONPs using the biomass filtrate of endophytic Xylaria arbuscula isolated from Blumea axillaris Linn. and to evaluate their biological properties. The characterisation of the biosynthesized ZnO-NPs was done utilising both spectroscopic and microscopic methods. The bioinspired NPs showed a surface plasmon peak at 370 nm; SEM and TEM micrographs illustrated the hexagonal organisation; XRD spectra proved the crystalline phase as hexagonal wurtzite; EDX analysis confirmed the presence of zinc and oxygen atoms; and the zeta potential analysis proved the stability of ZnONPs. In addition, they also demonstrated significant concentration-dependent inhibition of antimicrobial, antioxidant, anti-inflammatory, and antidiabetic potential in comparison with the reference drugs. In vitro cytotoxicity and wound healing potential of ZnONPs were examined in L929 cell lines, illustrating that they accelerated the wound healing process by roughly 95.37 ± 1.12% after a 24-h exposure to ZnONPs. The photocatalytic activity of the ZnONPs was examined by degrading the methylene blue dye under solar irradiation. In conclusion, our outcomes showed that mycosynthesized ZnONPs possessed potent bioactivity and could be an excellent choice for biomedical applications.
Randomized Phase 3 trial demonstrating high efficacy, favourable safety and convenience of a novel calcipotriol and betamethasone dipropionate cream for the treatment of psoriasis

The fixed dose combination of calcipotriene (CAL) and betamethasone dipropionate (BDP) is a well‐established topical treatment option for psoriasis based on strong scientific rationale for the single agents having complementary efficacy and safety. CAL/BDP PAD‐cream is an easily spreadable cream based on PAD Technology™, an innovative formulation and drug delivery system.
Egeria densa remediates the aquatic environment and reduces 14C-deltamethrin bioaccumulation in Danio rerio

Abstract Deltamethrin is an insecticide with high toxicity to non-target aquatic organisms. Environment-friendly alternatives to removing insecticides from water bodies, like phytoremediation, require species to uptake and/or dissipate pesticides from water. Our research investigated the ability of Egeria densa plants to absorb and dissipate 14C-deltamethrin from water, and bioaccumulation in Danio rerio. The variables were four densities of E. densa (0, 234, 337, and 468 g dry weight m−3), in tanks with seven adults of D. rerio, with three replicates. Dissipation was evaluated at 0, 24, 48, 72, and 96 h after application (HAA). After 96 HAA, the uptake of 14C-deltamethrin by plants and accumulation in fish were assessed. The E. densa increased 14C-deltamethrin dissipation and reduced bioaccumulation in zebrafish. The DT50 decreased 3-fold in treatments with 337 and 468 g m−3 of E. densa. The plants absorbed 32% of the 14C-deltamethrin applied, regardless of plant density. The bioaccumulation in fish was 8.21% without E. densa and only 1% in treatments with 468 g m−3 of plants. These results suggest phytoremediation using E. densa is a possible alternative to removing deltamethrin from water and reducing the accumulation in non-target organisms, reducing the environmental impact of insecticides in aquatic ecosystems.
Solid amorphous formulations for enhancing solubility and inhibiting Erlotinib crystallization during gastric-to-intestinal transfer

Abstract The objective of this study was to improve the solubility and inhibit the crystallisation during the gastric-to-intestinal transfer of Erlotinib (ERL), a small molecule kinase inhibitor (smKI) compound class, which is classified as class II drug in the Biopharmaceutical Classification System (BCS). A screening approach combining different parameters (solubility in aqueous media, inhibitory effect of drug crystallisation from supersaturated drug solutions) was applied to selected polymers for the development of solid amorphous dispersions of ERL. ERL solid amorphous dispersions formulations were then prepared with 3 different polymers (Soluplus®, HPMC-AS-L, HPMC-AS-H) at a fixed drug: polymer ratio (1:4) by two different production methods (spray drying and hot melt extrusion). The spray-dried particles and cryo-milled extrudates were characterized by thermal properties, shape and particle size, solubility and dissolution behavior in aqueous media. The influence of the manufacturing process on these solid characteristics was also identified during this study. Based on the obtained results, it is concluded that the cryo-milled extrudates of HPMC-AS-L displayed better performance (enhanced solubility, reduced ERL crystallization during the simulated gastric-to-intestinal transfer) and represents a promising amorphous solid dispersion formulation for oral administration of ERL.
A novel fully covered metal stent for unresectable malignant distal biliary obstruction: results of a multicenter prospective study.

Background/Aims Endoscopic self-expandable metal stent (SEMS) placement is currently the standard technique for treating unresectable malignant distal biliary obstructions (MDBO). Therefore, covered SEMS with longer stent patency and fewer migrations are required. This study aimed to assess the clinical performance of a novel, fully covered SEMS for unresectable MDBO. Methods This was a multicenter single-arm prospective study. The primary outcome was a non-obstruction rate at 6 months. The secondary outcomes were overall survival (OS), recurrent biliary obstruction (RBO), time to RBO (TRBO), technical and clinical success, and adverse events. Results A total of 73 patients were enrolled in this study. The non-obstruction rate at 6 months was 61%. The median OS and TRBO were 233 and 216 days, respectively. The technical and clinical success rates were 100% and 97%, respectively. Furthermore, the rate of occurrence of RBO and adverse events was 49% and 21%, respectively. The length of bile duct stenosis (<2.2 cm) was the only significant risk factor for stent migration. Conclusions The non-obstruction rate of a novel fully covered SEMS for MDBO is comparable to that reported earlier but shorter than expected. Short bile duct stenosis is a significant risk factor for stent migration.
Controlling modified Tardieu scale assessment speeds to match joint angular velocities during walking impacts spasticity assessment outcomes

Objective To investigate whether tailoring the speed of the Modified Tardieu Scale to reflect an individual's joint angular velocity during walking influences spasticity assessment outcomes. Design Observational trial. Setting Inpatient and outpatient neurological hospital department. Subjects Ninety adults with lower-limb spasticity. Interventions N/A. Main measures The Modified Tardieu Scale was used to assess the gastrocnemius, soleus, hamstrings and quadriceps. The V1 (slow) and V3 (fast) movements were completed as per standardised testing. Two additional assessments were completed, reflecting joint angular velocities during walking based on (i) a healthy control database (controlled velocity) and (ii) the individual's real-time joint angular velocities during walking (matched velocity). The agreement was compared using Cohen's and Weighted Kappa statistics, sensitivity and specificity. Results There was poor agreement when rating trials as spastic or not spastic at the ankle joint (Cohen's Kappa = 0.01–0.17). Trials were classified as spastic during V3 and not spastic during the controlled conditions in 81.6–85.1% of trials when compared to stance phase dorsiflexion angular velocities and 48.0–56.4% when compared to swing phase dorsiflexion angular velocities. The severity of muscle reaction demonstrated poor agreement at the ankle (Weighted Kappa = 0.01–0.28). At the knee, there was a moderate-excellent agreement between the V3 and controlled conditions when rating a trial as spastic or not spastic (Cohen's Kappa = 0.66–0.84) and excellent agreement when comparing severity (Weighted Kappa = 0.73–0.94). Conclusion The speed of assessment impacted spasticity outcomes. It is possible that the standardised protocol may overestimate the impact spasticity has on walking, especially at the ankle.
What are Effective Strategies to Reduce Low-Value Care? An Analysis of 121 Randomized Deimplementation Studies

Supplemental Digital Content is Available in the Text. ABSTRACT Background: Low-value care is healthcare leading to no or little clinical benefit for the patient. The best (combinations of) interventions to reduce low-value care are unclear. Purpose: To provide an overview of randomized controlled trials (RCTs) evaluating deimplementation strategies, to quantify the effectiveness and describe different combinations of strategies. Methods: Analysis of 121 RCTs (1990–2019) evaluating a strategy to reduce low-value care, identified by a systematic review. Deimplementation strategies were described and associations between strategy characteristics and effectiveness explored. Results: Of 109 trials comparing deimplementation to usual care, 75 (69%) reported a significant reduction of low-value healthcare practices. Seventy-three trials included in a quantitative analysis showed a median relative reduction of 17% (IQR 7%–42%). The effectiveness of deimplementation strategies was not associated with the number and types of interventions applied. Conclusions and Implications: Most deimplementation strategies achieved a considerable reduction of low-value care. We found no signs that a particular type or number of interventions works best for deimplementation. Future deimplementation studies should map relevant contextual factors, such as the workplace culture or economic factors. Interventions should be tailored to these factors and provide details regarding sustainability of the effect.
Danggui-Buxue decoction alleviated vascular senescence in mice exposed to chronic intermittent hypoxia through activating the Nrf2/HO-1 pathway

Abstract Context As a major risk factor for cardiovascular diseases (CVD), Obstructive sleep apnea (OSA) is characterized by chronic intermittent hypoxia (CIH). Recent studies indicated that the increased cardiovascular risk in patients with OSA may be mediated by accelerated vascular senescence. Danggui-Buxue decoction (DBD) has been used for treating cardiovascular diseases, but its mechanism of vascular senescence regulation is still unclear. Objective To investigate the effect of DBD on vascular senescence in mice exposed to CIH and to explore the role of the Nrf2/HO-1 pathway. Materials and methods C57BL/6N mice were randomly divided into Normoxia control group (CON), CIH (21%-5% O2, 20 times/h, 8 h/d) exposed group (CIH), and DBD treatment group (intragastrically treated with 2.34, 4.68, or 9.36 g/kg/day of DBD separately for 12 weeks as DBL, DBM, or DBH). Blood pressure, cardiac and vascular function, vascular senescence, inflammation response, oxidative stress, and Nrf2/HO-1 expression were determined. Results DBD (4.68 and 9.36 g/kg) significantly decreased Tail-cuff blood pressure, increased left ventricular systolic function, and alleviated arterial stiffness and vasorelaxation dysfunction in mice exposed to CIH. DBD treatment reduced SA-β-gal activity, decreased p16 (0.68-fold, 0.62-fold), P21 (0.58-fold, 0.52-fold), and p53 expressions (0.67-fold, 0.65-fold), and increased SIRT1 expression (2.22-fold, 2.98-fold) in the aortic. DBD treatment decreased IL-6, NF-κB, and TNF-α expressions, decreased MDA but increased SOD levels, and increased Nrf2 (1.8-fold, 1.89-fold) and HO-1 (2.25-fold, 2.43-fold) expression. Discussion and conclusions DBD could attenuate vascular senescence accelerated by CIH exposure through inhibiting inflammatory response and oxidative stress by activating the Nrf2/HO-1 pathway.