Miracle-dz/UniFAR-FTUs huggingface dataset:
Accounting of Receptor Flexibility in Ultra-Large Virtual Screens with VirtualFlow Using a Grey Wolf Optimization Method

Structure-based virtual screening approaches have the ability to dramatically reduce the time and costs associated to the discovery of new drug candidates. Studies have shown that the true hit rate of virtual screenings improves with the scale of the screened ligand libraries. Therefore, we have recently developed an open source drug discovery platform (VirtualFlow), which is able to routinely carry out ultra-large virtual screenings. One of the primary challenges of molecular docking is the circumstance when the protein is highly dynamic or when the structure of the protein cannot be captured by a static pose. To accommodate protein dynamics, we report the extension of VirtualFlow to allow the docking of ligands using a grey wolf optimization algorithm using the docking program GWOVina, which substantially improves the quality and efficiency of flexible receptor docking compared to AutoDock Vina. We demonstrate the linear scaling behavior of VirtualFlow utilizing GWOVina up to 128 000 CPUs. The newly supported docking method will be valuable for drug discovery projects in which protein dynamics and flexibility play a significant role.
Evaluating Cognitive/Emotional and Behavioral Mediators of Oral Health Outcomes in Vulnerable Older Adults

Inconsistent outcomes of oral hygiene interventions require testable theories combining cognitive and behavioral domains to guide intervention and improve results. This article evaluates the integrated model as a cognitive-behavioral approach to improve oral health clinical outcomes in ethnically diverse low-income older adults. Baseline data from a clinical trial utilizing the integrative model (IM) model evaluated predictors of gingival index (GI) and plaque score (PS). Individual logistic regression was performed for all predictors in relation to GI and PS. Multiple logistic regression was performed with significant predictors of GI and PS only. Greater locus of control and more brushing predicted lower GI; greater locus of control predicted lower PS. Both cognitive and behavioral domains impact GI, requiring more prolonged effort for improvement while locus of control, a cognitive variable, predicts PS, immediately improved by daily brushing/flossing. A streamlined IM including locus of control and tooth brushing should improve oral hygiene of low-income older adults.
The role of extracellular matrix phosphorylation on energy dissipation in bone

Protein phosphorylation, critical for cellular regulatory mechanisms, is implicated in various diseases. However, it remains unknown whether heterogeneity in phosphorylation of key structural proteins alters tissue integrity and organ function. Here, osteopontin phosphorylation level declined in hypo- and hyper- phosphatemia mouse models exhibiting skeletal deformities. Phosphorylation increased cohesion between osteopontin polymers, and adhesion of osteopontin to hydroxyapatite, enhancing energy dissipation. Fracture toughness, a measure of bone’s mechanical competence, increased with ex-vivo phosphorylation of wildtype mouse bones and declined with ex-vivo dephosphorylation. In osteopontin-deficient mice, global matrix phosphorylation level was not associated with toughness. Our findings suggest that phosphorylated osteopontin promotes fracture toughness in a dose-dependent manner through increased interfacial bond formation. In the absence of osteopontin, phosphorylation increases electrostatic repulsion, and likely protein alignment and interfilament distance leading to decreased fracture resistance. These mechanisms may be of importance in other connective tissues, and the key to unraveling cell–matrix interactions in diseases.
Advances in the Deformation and Failure of Concrete Pavement under Coupling Action of Moisture, Temperature, and Wheel Load

The deformation and cracking of concrete will lead to various deterioration processes, which will greatly reduce the durability and service life of the concrete pavement. The relating previous studies and analysis revealed that the coupling action of environmental temperature, moisture, and wheel load will cause cracking and seriously affect the normal service and durability of pavement concrete. This paper presents theoretical and numerical state-of-the-art information in the field of deformation and failure of pavement concrete under coupling action of moisture, temperature, and wheel load and draws some conclusions. (a) Concrete is a typical porous material, moisture and heat transfer theory has obtained enough data to simulate the hygro-thermo properties of concrete, and the relationship between moisture and heat is very clear. (b) There are few studies on concrete pavement or airport pavement considering the coupling action of moisture, temperature, and wheel load. (c) Concrete pavement is subjected to hygro-thermal-mechanical coupling action in service, which has the characteristics of a similar period and its possible fatigue effect. (d) COMSOL software has certain advantages for solving the coupled hygro-thermal-mechanical of concrete.
Gender Differences in Psychological Symptoms and Psychotherapeutic Processes in Japanese Children

Gender differences have been documented in the prevalence of psychological symptoms. Tic disorders and autism spectrum disorder (ASD) are more common in male clinical samples, while selective mutism and trichotillomania are more common in female clinical samples. In a review of 84 published case studies of Japanese children, this study explored gender differences in the prevalence of four categories of symptoms and expressions made in therapy for tics, selective mutism, autism spectrum disorder (ASD), and trichotillomania. Case studies were evaluated using both qualitative coding and statistical analysis. The findings were mostly consistent with epidemiological surveys and empirical research on adults. The gender differences in symptom prevalence and their expression could be summarized as differences in more direct aggression for boys versus indirect aggression for girls. The objective and progress in the therapy were to control impulsive energy for boys and to express energy for girls.
Natural Polysaccharide Carriers in Brain Delivery: Challenge and Perspective

Targeted drug delivery systems represent valuable tools to enhance the accumulation of therapeutics in the brain. Here, the presence of the blood brain barrier strongly hinders the passage of foreign substances, often limiting the effectiveness of pharmacological therapies. Among the plethora of materials used for the development of these systems, natural polysaccharides are attracting growing interest because of their biocompatibility, muco-adhesion, and chemical versatility which allow a wide range of carriers with tailored physico-chemical features to be synthetized. This review describes the state of the art in the field of targeted carriers based on natural polysaccharides over the last five years, focusing on the main targeting strategies, namely passive and active transport, stimuli-responsive materials and the administration route. In addition, in the last section, the efficacy of the reviewed carriers in each specific brain diseases is summarized and commented on in terms of enhancement of either blood brain barrier (BBB) permeation ability or drug bioavailability in the brain.
Date seeds alleviate behavioural and neuronal complications of metabolic syndrome in rats

Abstract Unhealthy dietary habits can play a crucial role in metabolic damages, promoting alteration of neural functions through the lifespan. Recently, dietary change has been perceived as the first line intervention in prevention and/or treatment of metabolic damages and related diseases. In this context, our study was designed to assess the eventual therapeutic effect of date seeds administration on memory and learning and on neuronal markers in a rat Metabolic Syndrome model. For this purpose, 32 adult male Wistar rats were fed with standard diet or high-fat high-sugar diet during ten weeks. After this, 16 rats were sacrified and the remaining rats received an oral administration of 300 mg of date seeds/kg of body weight during four supplementary weeks. Before sacrifice, we evaluate cognitive performances by the Barnes maze test. Afterwards, neuronal, astrocytic, microtubular and oxidative markers were investigated by immunoblotting methods. In Metabolic syndrome rats, results showed impairment of spatial memory and histological alterations. We identified neuronal damages in hippocampus, marked by a decrease of NeuN and an increase of GFAP and pTau396. Finally, we recorded an increase in protein oxidation and lipid peroxidation, respectively identified by an up-regulation of protein carbonyls and 4-HNe. Interestingly, date seeds administration improved these behavioural, histological, neuronal and oxidative damages highlighting the neuroprotective effect of this natural compound. Liquid Chromatography-Mass Spectrometry (LC-MS) identified, in date seeds, protocatechuic acid, caffeoylshikimic acid and vanillic acid, that could potentially prevent the progression of neurodegenerative diseases, acting through their antioxidant properties.
External Validation of a Population-Based Prediction Model for High Healthcare Resource Use in Adults

Predicting high healthcare resource users is important for informing prevention strategies and healthcare decision-making. We aimed to cross-provincially validate the High Resource User Population Risk Tool (HRUPoRT), a predictive model that uses population survey data to estimate 5 year risk of becoming a high healthcare resource user. The model, originally derived and validated in Ontario, Canada, was applied to an external validation cohort. HRUPoRT model predictors included chronic conditions, socio-demographics, and health behavioural risk factors. The cohort consisted of 10,504 adults (≥18 years old) from the Canadian Community Health Survey in Manitoba, Canada (cycles 2007/08 and 2009/10). A person-centred costing algorithm was applied to linked health administrative databases to determine respondents’ healthcare utilization over 5 years. Model fit was assessed using the c-statistic for discrimination and calibration plots. In the external validation cohort, HRUPoRT demonstrated strong discrimination (c statistic = 0.83) and was well calibrated across the range of risk. HRUPoRT performed well in an external validation cohort, demonstrating transportability of the model in other jurisdictions. HRUPoRT’s use of population survey data enables a health equity focus to assist with decision-making on prevention of high healthcare resource use.
Phone-based outpatients’ follow-up in mental health centers during the COVID-19 quarantine

Background: The current COVID-19 pandemic is affecting mental health of global population and, particularly, of people suffering from preexisting mental disorders. Aims: This study aims to report on findings from a phone-based clinical follow-up conducted in two large catchment areas in Italy and Paraguay, during the COVID-19 lockdown, in order to provide psychiatric assessments and measure the level of stress related to the quarantine in a large sample of psychiatric outpatients. Methods: A clinical phone-based follow-up has been conducted in two large catchment areas in the province of Chieti (Vasto, Italy) and City of Asunción (Paraguay), during the COVID-19 national lockdown. The following rating scales have been employed: Hamilton Anxiety Rating Scale (HAM-A); Hamilton Depression Rating Scale (HAM-D); 18-items Brief Psychiatric Rating Scale (BPRS-18). The psychological distress related to the outbreak has been assessed employing the Impact of Event Scale – Revised (IES-R). Results: A total of 110 outpatients were consecutively included and followed among those reporting a stable phase of illness before the COVID-19 lockdown. Findings confirmed a significant increase of general psychopathology, anxiety and fear as well as mild levels of stress related to the quarantine. Also, significant weight gain during the lockdown was detected among patients. Conclusions: This study confirmed the impact of COVID-19 lockdown on mental health of people suffering from psychiatric disorders and may also add evidence on the employment of digital psychiatry in the current pandemic.
Fundamental differences in physiology of Bordetella pertussis dependent on the two-component system Bvg revealed by gene essentiality studies

The identification of genes essential for a bacterium’s growth reveals much about its basic physiology under different conditions. Bordetella pertussis , the causative agent of whooping cough, adopts both virulent and avirulent states through the activity of the two-component system, Bvg. The genes essential for B. pertussis growth in vitro were defined using transposon sequencing, for different Bvg-determined growth states. In addition, comparison of the insertion indices of each gene between Bvg phases identified those genes whose mutation exerted a significantly different fitness cost between phases. As expected, many of the genes identified as essential for growth in other bacteria were also essential for B. pertussis . However, the essentiality of some genes was dependent on Bvg. In particular, a number of key cell wall biosynthesis genes, including the entire mre/mrd locus, were essential for growth of the avirulent (Bvg minus) phase but not the virulent (Bvg plus) phase. In addition, cell wall biosynthesis was identified as a fundamental process that when disrupted produced greater fitness costs for the Bvg minus phase compared to the Bvg plus phase. Bvg minus phase growth was more susceptible than Bvg plus phase growth to the cell wall-disrupting antibiotic ampicillin, demonstrating the increased susceptibility of the Bvg minus phase to disruption of cell wall synthesis. This Bvg-dependent conditional essentiality was not due to Bvg-regulation of expression of cell wall biosynthesis genes; suggesting that this fundamental process differs between the Bvg phases in B. pertussis and is more susceptible to disruption in the Bvg minus phase. The ability of a bacterium to modify its cell wall synthesis is important when considering the action of antibiotics, particularly if developing novel drugs targeting cell wall synthesis.
Congenital diaphragmatic hernia repair in patients requiring extracorporeal membrane oxygenation: are outcomes better with repair on ECMO or after decannulation?

A best evidence topic in cardiac surgery was written according to a structured protocol. The question addressed was whether congenital diaphragmatic hernia repair outcomes are better before or after decannulation in infants requiring extracorporeal membrane oxygenation (ECMO). A total of 884 papers were found using the reported search, of which 9 represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated. We conclude that infants with congenital diaphragmatic hernia requiring ECMO should undergo a trial of weaning and aim for post-decannulation repair, as this has been associated with improved survival, shorter ECMO duration and fewer bleeding complications. However, if weaning of ECMO is unsuccessful, the patient should ideally undergo early on-ECMO repair (within 72 h of cannulation), which has been associated with improved survival, less bleeding, shorter ECMO duration and fewer circuit changes compared to late on-ECMO repair. Anticoagulation protocols including perioperative administration of aminocaproic acid or tranexamic acid, as well as close perioperative monitoring of coagulation parameters have been associated with reduced bleeding risk with on-ECMO repairs.
Non-Destructive Prediction of Titratable Acidity and Taste Index Properties of Gala Apple Using Combination of Different Hybrids ANN and PLSR-Model Based Spectral Data

Non-destructive estimation of the internal properties of fruits and vegetables is very important, because better management can be provided for subsequent operations. Researchers and scientists around the world are focusing on non-destructive methods because if they are developed and commercialized, there will be an impressive change in the food industry. In this regard, this paper aims to present a non-destructive method based on Vis-NIR spectral data. The different stages of the proposed algorithm are: (1) Collection of samples of Gala apples, (2) Spectral data extraction by spectroscopy, (3) Pre-processing of spectral data, (4) Measurement of chemical properties of titratable acidity (TA) and taste index, (5) Selection of key wavelengths using hybrid artificial neural network-firefly algorithm (ANN-FA), (6) Non-destructive estimation of the properties using two methods of hybrid ANN- Particle swarm optimization algorithm and partial least squares regression. For considering the reliability of methods for estimating the chemical properties, the prediction operation was executed in 300 iterations. The results represented that the mean and standard deviation of the correlation coefficient and the root mean square error of hybrid ANN-PSO and PLSR for TA were 0.9095 ± 0.0175, 0.0598 ± 0.0064, 0.834 ± 0.0313 and 0.0761 ± 0.0061 respectively. These values for taste index were 0.918 ± 0.02, 3.2 ± 0.39, 0.836 ± 0.033 and 4.09 ± 0.403, respectively. Therefore, it can be concluded that the hybrid ANN-PSO has a better performance for non-destructive prediction of the two mentioned chemical properties than the PLSR method. In general, the proposed method can predict the chemical properties of TA and taste index non-destructively, which is very useful for mechanized harvesting and management of post-harvest operation.
Fabrication of a 3D Multi-Depth Reservoir Micromodel in Borosilicate Glass Using Femtosecond Laser Material Processing

Micromodels are ideal candidates for microfluidic transport investigations, and they have been used for many applications, including oil recovery and carbon dioxide storage. Conventional fabrication methods (e.g., photolithography and chemical etching) are beset with many issues, such as multiple wet processing steps and isotropic etching profiles, making them unsuitable to fabricate complex, multi-depth features. Here, we report a simpler approach, femtosecond laser material processing (FLMP), to fabricate a 3D reservoir micromodel featuring 4 different depths—35, 70, 140, and 280 µm, over a large surface area (20 mm × 15 mm) in a borosilicate glass substrate. The dependence of etch depth on major processing parameters of FLMP, i.e., average laser fluence (LFav), and computer numerically controlled (CNC) processing speed (PSCNC), was studied. A linear etch depth dependence on LFav was determined while a three-phase exponential decay dependence was obtained for PSCNC. The accuracy of the method was investigated by using the etch depth dependence on PSCNC relation as a model to predict input parameters required to machine the micromodel. This study shows the capability and robustness of FLMP to machine 3D multi-depth features that will be essential for the development, control, and fabrication of complex microfluidic geometries.
Timeliness of immunisation with the pentavalent vaccine at different levels of the health care system in the Lao People’s Democratic Republic: A cross-sectional study

Background The timely administration of vaccines is considered to be important for both individual and herd immunity. In this study, we investigated the timeliness of the diphtheria-tetanus-whole cell pertussis-hepatitis B-Haemophilus influenzae type b (pentavalent) vaccine, scheduled at 6, 10 and 14 weeks of age in the Lao People’s Democratic Republic. We also investigated factors associated with delayed immunization. Methods 1162 children aged 8–28 months who had received the full course of the pentavalent vaccine at different levels of the health care system were enrolled. Vaccination dates documented in hospital records and/or immunisation cards were recorded. Age at vaccination and time intervals between doses were calculated. Predictors for timely completion with the pentavalent vaccine at 24 weeks were assessed by bivariate and multivariable analyses. Results Several discrepancies in dates between vaccination documents were observed. In general, vaccination with the pentavalent vaccine was found to be delayed, especially in health care settings below the provincial hospital level. Compared to the central hospital level, less participants who were vaccinated at the district/health center level received the third dose by 16 (48% at the central hospital level vs. 7.1% at the district and 12.4% at the health center level) and 24 weeks of age (94.4% at the central hospital level vs 64.6% at the district-outreach and 57.4% at the health center level) respectively. In logistic regression analyses, lower education level of the mother as well as vaccination by outreach service, were independently associated with delayed completion of vaccination. Conclusion We observed a general delay of vaccination, especially at lower ranked facilities, which correlated with indicators of poor access to health services. This highlights the need for further improving health equity in rural areas. Age-appropriate vaccination should become a quality indicator for the national immunization programme. In addition, we recommend further training of the health care staff regarding the importance of reliable documentation of dates.
Facial nerve baroparesis during airflight: a case report and literature review

Abstract Background Facial nerve baroparesis is a rare phenomenon which has been reported during flight. It is thought to occur due to ischaemic neuropraxia on the facial nerve as middle-ear pressure increases in the presence of Eustachian tube dysfunction and force is transmitted through a dehiscent facial nerve canal. Method This study presents an aviation-associated, right-sided facial nerve palsy as well as presenting the results of a systematic review that was performed on the available literature using Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Full-text articles from Medline, PubMed and Embase were used, as well as associated reference lists. This study systematically reviews the literature to discuss presentation, investigations performed and an approach to management of this rare condition. Results This study identified 23 cases in the literature (including the case presented in this study) of facial nerve baroparesis. Conclusion Facial nerve baroparesis is a mostly temporary rare phenomenon that can be managed effectively with ventilation tube insertion. In the event of long-standing facial nerve palsy after descent of the aircraft, urgent myringotomy should be performed to prevent permanent facial nerve damage.