Miracle-dz/UniFAR-FTUs huggingface dataset:
Improved Method of Structure-Based Virtual Screening via Interaction-Energy-Based Learning

Virtual screening is a promising method for obtaining novel hit compounds in drug discovery. It aims to enrich potentially active compounds from a large chemical library for further biological experiments. However, the accuracy of current virtual screening methods is insufficient. In this study, we develop a new virtual screening method named Similarity of Interaction Energy VEctor Score (SIEVE-Score), in which protein-ligand interaction energies are extracted to represent docking poses for machine learning. SIEVE-Score offers substantial improvements compared to other state-of-the-art virtual screening methods, namely, other machine-learning-based scoring functions, interaction fingerprints, and docking software, for the enrichment factor 1% results on the Directory of Useful Decoys, Enhanced (DUD-E). The screening results are also human-interpretable in the form of important interactions for distinguishing between active and inactive compounds. The source code is available at https://github.com/sekijima-lab/SIEVE-Score .
Spatial heterogeneity of prion gene polymorphisms in an area recently infected by chronic wasting disease

ABSTRACT Genetic variability in the prion protein (Prnp) gene influences host susceptibility to many pathogenic prion diseases. Understanding the distribution of susceptible Prnp variants and determining factors influencing spatial genetic patterns are important components of many chronic wasting disease mitigation strategies. Here, we describe Prnp variability in white-tailed deer (Odocoileus virginianus) from the Mid-Atlantic region of the United States of America, an area with a recent history of infection and low disease incidence. This population is characterized by lower rates of polymorphism and significantly higher frequencies of the more susceptible 96GG genotype compared to previously surveyed populations. The prevalence of the most susceptible genotypes at disease-associated loci did vary among subregions, indicating that populations have innate differences in genotype-dictated susceptibility.
A Phase-Invariant Linear Torque-Angle-Velocity Relation Hidden in Human Walking Data

Human walking is a sequential composition of gait cycles. Each gait cycle can be divided into four motion phases separated by heel strike and toe off. A classical conjecture in the control of lower limb assistive devices, state-of-the-art prostheses, and exoskeletons, is that each motion phase requires a different controller, such that adequate control of locomotion requires at least four distinct controllers. In this paper, we show that the joint torque versus joint angle and velocity relation hidden in the normal human walking data can be remarkably well represented with a single linear controller. In particular, based on the analysis of seven healthy subjects, we show that a one phase 20±5% sparse linear relation between the joint torques, angles and velocities explains 96.1±0.4% (mean±sem) of the normal human walking data (sparsity defines the percentage of zero control parameters). This result is comparable to what can be achieved using a significantly more complex four-phase non-sparse linear controller which explains 98.7±0.2% of the walking data, and is significantly better than a one-phase fully sparsified linear controller that could only explain 11.9±0.2% of the same data. Based on these results, we posit that the proposed phase-invariant sparse linear controller provides one of the simplest representations that can adequately explain the joint torque, angle and velocity relation present in the human walking data. The resulting control structure may be useful in developing simple yet competent phase-invariant controllers for next-generation prostheses and exoskeleton devices used for human assistance and augmentation.
The Potential Clinical Implications and Importance of Drug Interactions Between Anticancer Agents and Cannabidiol in Patients With Cancer

The objective of this review was to identify and examine the pharmacokinetic and pharmacodynamic interactions between cannabidiol (CBD)-only products, such as CBD oil, and anticancer agents. A literature search of PubMed (1980 to September 2018) and the Cochrane Collection (1980 to September 2018) was performed using the following search terms: “cannabidiol,” “cancer,” “cannabis,” “marijuana,” and “interaction,” as well as any combination of these terms. Literature was excluded if it did not appear in the search when limited to the “full text” filter on PubMed, if it was not published in the English language, or if it did not explore potential pharmacodynamic or pharmacokinetic interactions of CBD and anticancer agents. There were 10 studies that met these inclusion criteria. The majority of the facts regarding the interactions with CBD were found using in vitro studies and the true in vivo implications are not well-known. Minimal data were available regarding the interactions between CBD and anticancer agents. However, pharmacists should always consider the possibility of interactions and their consequences whenever they are aware of a patient using CBD products.
Establishment of tooth blood supply and innervation is developmentally regulated and takes place through differential patterning processes

Teeth are richly supported by blood vessels and peripheral nerves. The aim of this study was to describe in detail the developmental time‐course and localization of blood vessels during early tooth formation and to compare that to innervation, as well as to address the putative role of vascular endothelial growth factor (VEGF), which is an essential regulator of vasculature development, in this process. The localization of blood vessels and neurites was compared using double immunofluorescence staining on sections at consecutive stages of the embryonic (E) and postnatal (PN) mandibular first molar tooth germ (E11‐PN7). Cellular mRNA expression domains of VEGF and its signaling receptor VEGFR2 were studied using sectional radioactive in situ hybridization. Expression of VEGF mRNA and the encoded protein were studied by RT‐PCR and western blot analysis, respectively, in the cap and early bell stage tooth germs, respectively. VEGFR2 was immunolocalized on tooth tissue sections. Smooth muscle cells were investigated by anti‐alpha smooth muscle actin (αSMA) antibodies. VEGF showed developmentally regulated epithelial and mesenchymal mRNA expression domains including the enamel knot signaling centers that correlated with the growth and navigation of the blood vessels expressing Vegfr2 and VEGFR2 to the dental papilla and enamel organ. Developing blood vessels were present in the jaw mesenchyme including the presumptive dental mesenchyme before the appearance of the epithelial dental placode and dental neurites. Similarly, formation of a blood vessel plexus around the bud stage tooth germ and ingrowth of vessels into dental papilla at E14 preceded ingrowth of neurites. Subsequently, pioneer blood vessels in the dental papilla started to receive smooth muscle coverage at the early embryonic bell stage. Establishment and patterning of the blood vessels and nerves during tooth formation are developmentally regulated, stepwise processes that likely involve differential patterning mechanisms. Development of tooth vascular supply is proposed to be regulated by local, tooth‐specific regulation by epithelial–mesenchymal tissue interactions and involving tooth target expressed VEGF signaling. Further investigations on tooth vascular development by local VEGF signaling, as well as how tooth innervation and development of blood vessels are integrated with advancing tooth organ formation by local signaling mechanisms, are warranted.
A new approach to estimate ultrafine particle respiratory deposition

Abstract Ultrafine particles (UFPs) in workplaces have been and continue to be an important occupational health concern. The inhalation and the consequent deposition of UFPs in workers’ lower airways can lead to many adverse health effects. Therefore, it is vital to study the deposition of UFPs in the human respiratory tract from the viewpoint of occupational health. In this study, a set of physiologically representative human tracheobronchial airway replicas were made using high-resolution 3D printers, and a new approach that was distinct from the traditional methods was developed to apply these airway replicas in estimating UFP respiratory deposition. The results showed that UFP respiratory deposition could be readily and systematically measured by the differential-based approach. The results of this study imply the feasibility of developing a mobile aerosol lung deposition apparatus in the future for on-site workplace UFP respiratory deposition to evaluate the UFP inhalation dosimetry for workers in the real workplaces.
Genome-Wide Characterization of NBS-Encoding Genes in Watermelon and Their Potential Association with Gummy Stem Blight Resistance

Watermelon (Citrullus lanatus) is a nutritionally rich and economically important horticultural crop of the Cucurbitaceae family. Gummy stem blight (GSB) is a major disease of watermelon, which is caused by the fungus Didymella bryoniae, and results in substantial economic losses in terms of yield and quality. However, only a few molecular studies have focused on GSB resistance in watermelon. Nucleotide binding site (NBS)-encoding resistance (R) genes play important roles in plant defense responses to several pathogens, but little is known about the role of NBS-encoding genes in disease resistance in watermelon. The analyzed NBS-encoding R genes comprises several domains, including Toll/interleukin-1 receptor(TIR), NBS, leucine-rich repeat (LRR), resistance to powdery mildew8(RPW8) and coiled coil (CC), which are known to be involved in disease resistance. We determined the expression patterns of these R genes in resistant and susceptible watermelon lines at different time points after D. bryoniae infection by quantitative RT-PCR. The R genes exhibited various expression patterns in the resistant watermelon compared to the susceptible watermelon. Only six R genes exhibited consistent expression patterns (Cla001821, Cla019863, Cla020705, Cla012430, Cla012433 and Cla012439), which were higher in the resistant line compared to the susceptible line. Our study provides fundamental insights into the NBS-LRR gene family in watermelon in response to D. bryoniae infection. Further functional studies of these six candidate resistance genes should help to advance breeding programs aimed at improving disease resistance in watermelons.
Time Trends in Age at Menarche and Related Non-Communicable Disease Risk during the 20th Century in Mexico

Developed countries have shown a time trend towards a younger age at menarche (AAM), which is associated with increased risk of later obesity and non-communicable diseases. This study aimed to assess whether a time trend in AAM is associated with disease risk in Mexican women (n = 30,826), using data from the Mexican National Health Survey (2000). Linear and log binomial regression was used for nutritional and disease outcomes, while Welch–ANOVA was used to test for a time trend. AAM (in years) decreased over time (p < 0.001), with a maximal difference of 0.99 years between the 1920s (13.6 years) and 1980s (12.6 years ). AAM was negatively associated with weight (β = −1.01 kg; 95% CI −1.006, −1.004) and body mass index (BMI) (β = −1.01 kg/m2; −1.007, −1.006), and positively with height (β = 0.18 cm; 0.112, 0.231). AAM was associated with diabetes (RR = 0.95; 0.93, 0.98) and hypercholesterolemia (RR = 0.93; 0.90, 0.95), but not with hypertension, breast cancer or arthritis. In Mexico, AAM decreased significantly during the 20th century. AAM was inversely associated with adult weight and BMI, and positively with height. Women with a later AAM had a lower risk of diabetes and hypercholesterolemia.
Effect of Fish Oil Supplementation on Hepatic and Visceral Fat in Overweight Men: A Randomized Controlled Trial

Being overweight increases the risk of the development of metabolic conditions such as non-alcoholic fatty liver disease (NAFLD), which is itself an independent predictor of cardiovascular disease. Omega-3 polyunsaturated fatty acid (PUFA) supplementation is recommended for prevention of chronic disease, and is thought to reduce raised liver fat, yet there have been few randomized controlled trials with accurate measurement of liver fat. We assessed the effect of 12 weeks of supplementation with omega-3 PUFA from fish oil versus placebo on quantified liver fat, liver tests, and body composition including visceral adipose tissue (VAT) in a double-blind randomized controlled trial. Fifty apparently healthy overweight men (BMI 25.0–29.9 kg/m2; waist > 94 cm) were randomly allocated to consume fish oil (total daily dose: 1728 mg marine triglycerides, of which 588 mg EPA and 412 mg DHA, combined with 200 mg antioxidant, coenzyme Q10) or placebo (olive oil capsules) daily for 12 weeks. Liver fat was assessed using proton magnetic resonance spectroscopy. All outcomes were assessed at baseline and following 6 and 12 weeks of supplementation. Baseline liver fat was 4.6 ± 0.5% (range: 0.6 to 18.2%); 16 (32%) participants met the criteria for NAFLD (>5.5% liver fat). Repeated measures ANOVA revealed no significant time or group × time effect for fish oil versus placebo for liver fat, liver enzymes, anthropometry, or body composition including VAT (p > 0.05 for all), with similar finding for sub-analysis of participants with NAFLD. Omega-3 PUFA did not appear to be an effective agent for reducing liver fat in overweight men. The factors determining the health benefits of omega-3 PUFA supplementation on an individual level need to be clarified.
Is Capacity Building Training Effective for Changing Attitudes toward Health Inequalities? Experience from a Norway Grants Project in Lithuania

Background and Objectives: In 2014–2017, the Lithuanian University of Health Sciences and partners implemented the project, ‘Development of the Model for the Strengthening of the Capacities to Identify and Reduce Health Inequalities’, which was financed by The Norwegian Financial Mechanism 2009–2014 Public Health Initiatives Program. One of objectives of this project was to increase the awareness about public health and related specialist knowledge and skills in the field of health inequalities. This paper evaluates the effectiveness of capacity-training sessions on capacity building regarding increasing the awareness and knowledge that is needed for addressing health inequalities. Materials and Methods: Participants attending capacity-building seminars were asked to complete the same questionnaires before and after these training sessions. A total of 145 questionnaires were received (response rate 71.8%). The evaluation of changes in the pre-survey and post-survey responses in relation to a nonparametric analysis of two related samples was performed using the Wilcoxon test. Results: Respondents were asked to identify the general importance of health inequalities to the national public health agenda. The pre-training median of the survey was nine (minimum four; maximum 10), and post-training was 10 [minimum five; maximum 10] (p < 0.001). Unemployed, low-paid, and low-educated people were identified as the most vulnerable groups of society in terms of health inequalities. A more effective tobacco and alcohol control was identified as the most important inequality measure needed. An absolute majority of participants emphasized the need for intersectoral collaboration for the effective reduction of health inequalities. Conclusion: The findings from our study suggest that capacity-building sessions can be effective measures for increasing awareness of health inequalities. It is expected that the outcomes of these training opportunities will act as facilitators for further engagement and ongoing approaches to addressing health inequalities.
Gene-environment interaction impacts on heart development and embryo survival

ABSTRACT Congenital heart disease (CHD) is the most common type of birth defect. In recent years, research has focussed on identifying the genetic causes of CHD. However, only a minority of CHD cases can be attributed to single gene mutations. In addition, studies have identified different environmental stressors that promote CHD, but the additive effect of genetic susceptibility and environmental factors is poorly understood. In this context, we have investigated the effects of short-term gestational hypoxia on mouse embryos genetically predisposed to heart defects. Exposure of mouse embryos heterozygous for Tbx1 or Fgfr1/Fgfr2 to hypoxia in utero increased the incidence and severity of heart defects while Nkx2-5+/− embryos died within 2 days of hypoxic exposure. We identified the molecular consequences of the interaction between Nkx2-5 and short-term gestational hypoxia, which suggest that reduced Nkx2-5 expression and a prolonged hypoxia-inducible factor 1α response together precipitate embryo death. Our study provides insight into the causes of embryo loss and variable penetrance of monogenic CHD, and raises the possibility that cases of foetal death and CHD in humans could be caused by similar gene-environment interactions. Highlighted Article: Studies using Nkx2-5, Tbx1 and Fgfr1/Fgfr2 mutant mice reveal how a genetic predisposition to developing a heart defect can combine with short-term gestational hypoxia to cause defects and foetal death.
Low-risk isn't no-risk Perinatal treatments and the health of low-income newborns

We investigate the eﬀects of perinatal medical treatments on low-income newborns who are classiﬁed as low-risk. A policy rule in The Netherlands states that low-risk deliveries before week 37 should be supervised by physicians and later deliveries only by midwives with no physician present. This creates large discontinuities in the probability of receiving medical interventions only physicians are allowed to perform. Using a regression discontinuity design, we ﬁnd that babies born slightly before the week-37 cutoﬀ are signiﬁcantly less likely to die than babies born slightly later. Our data suggest that physician supervision of birth reduces the likelihood of adverse events such as fetal distress or emergency C-section. Our results indicate that low-income women beneﬁt from receiving a higher level of medical care even if no explicit risk factors have been recognized, pointing to challenges in identifying all high-risk pregnancies. “Back-of-the-envelope” calculations suggest this additional care is highly cost-eﬀective. The data include detailed information on the birth process. For each delivery, we observe the date and time of birth, type of birth attendant (midwife or OB/GYN), delivery location (home or hospital), method of delivery (vaginal, planned C-section, emergency C-section), use of interventions during vaginal delivery (labor augmentation, induction, use of forceps or vacuum), as well as the presence of complications during pregnancy or delivery. In the case of complications, we can observe the date and the reason for referral from midwife to an obstetrician. The data also provide rich background information on newborns (gender, gestational age in days, birth weight, parity, plurality) and basic demographic characteristics of mothers (age, ethnicity, 4-digit resi-dential postal code). We complement the individual-level Perined data with a secondary postal code-level data set from Statistics Netherlands (Kerncijfers postcodegebieden 2004). These data provide a snapshot of average characteristics in the postal code of residence of the mother as of January 1, 2004, such as average monthly household income, average area density, and the share of residents 0-15 years old. 6 or soon examining eﬀect week-37 rule on medical the then examine
Structural characterization of monoclonal antibodies targeting C-terminal Ser404 region of phosphorylated tau protein

ABSTRACT Targeting tau with immunotherapies is currently the most common approach taken in clinical trials of patients with Alzheimer’s disease. The most prominent pathological feature of tau is its hyperphosphorylation, which may cause the protein to aggregate into toxic assemblies that collectively lead to neurodegeneration. Of the phospho-epitopes, the region around Ser396/Ser404 has received particular attention for therapeutic targeting because of its prominence and stability in diseased tissue. Herein, we present the antigen-binding fragment (Fab)/epitope complex structures of three different monoclonal antibodies (mAbs) that target the pSer404 tau epitope region. Most notably, these structures reveal an antigen conformation similar to a previously described pathogenic tau epitope, pSer422, which was shown to have a β-strand structure that may be linked to the seeding core in tau oligomers. In addition, we have previously reported on the similarly ordered conformation observed in a pSer396 epitope, which is in tandem with pSer404. Our data are the first Fab structures of mAbs bound to this epitope region of the tau protein and support the existence of proteopathic tau conformations stabilized by specific phosphorylation events that are viable targets for immune modulation.
Characterization of Analgesic Actions of the Chronic Intrathecal Infusion of H‐Dmt‐D‐Arg‐Phe‐Lys‐NH2 in Rat

DMT‐DALDA (H‐Dmt‐D‐Arg‐Phe‐Lys‐NH2; Dmt = 2′,6′‐dimethyltyrosine) is a selective mu opioid agonist. We sought to characterize efficacy, tolerance, dependence and side‐effect profile when given by continuous intrathecal infusion.
Effect of Tabular and Icon Fact Box Formats on Comprehension of Benefits and Harms of Prostate Cancer Screening: A Randomized Trial

Background. Fact boxes employ evidence-based guidelines on risk communication to present benefits and harms of health interventions in a balanced and transparent format. However, little is known about their short- and long-term efficacy and whether designing fact boxes to present multiple outcomes with icon arrays would increase their efficacy. Method. In study 1, 120 men (30–75 y) completed a lab study. Participants were randomly assigned to 1 of 3 fact box formats on prostate cancer screening: a tabular fact box with numbers, a fact box with numbers and icon array, and a fact box with numbers, separate icon arrays, and text to describe each benefit and harm. Comprehension of information (while materials were present) and short-term knowledge recall were assessed. Study 2 recruited an online sample of 244 German men (40–75 y). Participants were randomly assigned to 1 of the 3 fact box formats or widely distributed health information, and knowledge was assessed at baseline, shortly after presentation, and at 6-mo follow-up, along with comprehension while materials were present. Results. In both studies, comprehension and knowledge-recall scores were similar when comparing tabular and icon fact boxes. In the 6-mo follow-up, this positive effect on knowledge recall disappeared. Fact boxes increased knowledge relative to baseline but did not affect decision intentions or perceptions of having complete information to make decisions. Conclusions. This study shows that fact boxes with and without icon arrays are equally effective at improving comprehension and knowledge recall over the short-term and are simple formats that can improve on current health information. Specifically, if fact boxes are used at the time or immediately before a decision is made, they promote informed decisions about prostate cancer screening.