Miracle-dz/UniFAR-FTUs huggingface dataset:
Trial Registration: Registered at ClinicalTrials.gov as “Personalized Indicators for Predicting Response to SSRI Treatment in Major Depression (The PRISE-MD Study)” NCT00917059 Prospective testing of a neurophysiologic biomarker for treatment decisions in major depressive disorder: the PRISE-MD tria

Management of Major Depressive Disorder (MDD) might be improved by a biomarker to predict whether a selected medication is likely to lead to remission. We previously reported on a quantitative electroencephalogram-based biomarker, the Antidepressant Treatment Response (ATR) index, that integrated recordings at baseline and after one week of treatment. The present study prospectively tested whether treatment directed by the biomarker increased the likelihood of remission; we hypothesized that continued treatment with a drug predicted to lead to remission (i.e., high ATR values) would be associated with better outcomes than if the drug was predicted not to lead to remission (i.e., low ATR values). We enrolled 180 adult outpatients with unipolar MDD from the community. After one week of escitalopram treatment to determine the biomarker, stratified randomization (high vs. low ATR) was used to assign subjects to either continued escitalopram or a switch to bupropion as a blinded control condition, for seven additional weeks. For the 73 evaluable subjects assigned to continued escitalopram treatment, the remission rate was significantly higher for those in whom ATR had predicted remission versus non-remission (60.4% vs. 30.0%, respectively, p=0.01). Accuracy was enhanced by combining 1-week depressive symptom change with ATR (68.6% vs 28.9%). This prospective validation study supports further development of the ATR biomarker, alone or together with early symptom change, to improve care by identifying individuals unlikely to remit with their current treatment, and support the decision to change treatment after one week rather than after failing a full, prolonged course of medication.
Pharmacotechnical Development of a Nasal Drug Delivery Composite Nanosystem Intended for Alzheimer’s Disease Treatment

Direct nose-to-brain delivery has been raised as a non-invasive powerful strategy to deliver drugs to the brain bypassing the blood-brain barrier (BBB). This study aimed at preparing and characterizing an innovative composite formulation, associating the liposome and hydrogel approaches, suitable for intranasal administration. Thermosensitive gel formulations were obtained based on a mixture of two hydrophilic polymers (Poloxamer 407, P407 and Poloxamer 188, P188) for a controlled delivery through nasal route via liposomes of an active pharmaceutical ingredient (API) of potential interest for Alzheimer’s disease. The osmolarity and the gelation temperature (T° sol-gel) of formulations, defined in a ternary diagram, were investigated by rheometry and visual determination. Regarding the issue of assays, a mixture composed of P407/P188 (15/1%, w/w) was selected for intranasal administration in terms of T° sol-gel and for the compatibility with the olfactory mucosal (280 ± 20 mOsmol, pH 6). Liposomes of API were prepared by the thin film hydration method. Mucoadhesion studies were performed by using mucin disc, and they showed the good natural mucoadhesive characteristics of in situ gel formulations, which increased when liposomes were added. The study demonstrated successful pharmacotechnical development of a promising API-loaded liposomes in a thermosensitive hydrogel intended for nasal Alzheimer’s disease treatment.
Fragment pose prediction using non-equilibrium candidate Monte Carlo and molecular dynamics simulations.

Part of early stage drug discovery involves determining how molecules may bind to the target protein. Through understanding where and how molecules bind, chemists can begin to build ideas on how to design improvements to increase binding affinities. In this retrospective study, we compare how computational approaches like docking, molecular dynamics (MD) simulations, and a non-equilibrium candidate Monte Carlo (NCMC) based method (NCMC+MD) perform in predicting binding modes for a set of 12 fragment-like molecules which bind to soluble epoxide hydrolase. We evaluate each method's effectiveness in identifying the dominant binding mode and finding any additional binding modes (if any). Then, we compare our predicted binding modes to experimentally obtained X-ray crystal structures. We dock each of the 12 small molecules into the apo-protein crystal structure and then run simulations up to 1 microsecond each. Small and fragment-like molecules likely have smaller energy barriers separating different binding modes by virtue of relatively fewer and weaker interactions relative to drug-like molecules, and thus likely undergo more rapid binding mode transitions. We expect, thus, to see more rapid transitions between binding modes in our study.
Possibilities and Limits of Computational Fluid Dynamics-Discrete Element Method Simulations in Process Engineering: A Review of Recent Advancements and Future Trends.

Fluid-solid systems play a major role in a wide variety of industries, from pharmaceutical and consumer goods to chemical plants and energy generation. Along with this variety of fields comes a diversity in apparatuses and applications, most prominently fluidized and spouted beds, granulators and mixers, pneumatic conveying, drying, agglomeration, coating, and combustion. The most promising approach for modeling the flow in these systems is the CFD-DEM method, coupling computational fluid dynamics (CFD) for the fluid phase and the discrete element method (DEM) for the particles. This article reviews the progress in modeling particle-fluid flows with the CFD-DEM method. A brief overview of the basic method as well as methodical extensions of it are given. Recent applications of this simulation approach to separation and classification units, fluidized beds for both particle formation and energy conversion, comminution units, filtration, and bioreactors are reviewed. Future trends are identified and discussed regarding their viability. Expected final online publication date for the Annual Review of Chemical and Biomolecular Engineering, Volume 11 is June 8, 2020. Please see http://www.annualreviews. org/page/journal/pubdates for revised estimates.
Vitamin D Status in Japanese Adults: Relationship of Serum 25-Hydroxyvitamin D with Simultaneously Measured Dietary Vitamin D Intake and Ultraviolet Ray Exposure

Vitamin D insufficiency/deficiency is prevalent worldwide. We investigated the effect of vitamin D intake and ultraviolet ray (UV) exposure on serum vitamin D concentration in Japan. A total of 107 healthy adult participants were recruited from Hokkaido (43° N) and Kumamoto (33° N) prefectures. All participants undertook surveys in both summer and winter. Serum 25-hydroxyvitamin D (25(OH)D3) was examined, and vitamin D intake was assessed with a diet history questionnaire. UV exposure was measured with a wearable UV dosimeter. Regression analysis was performed to investigate the relationship between these factors, with covariates such as sun avoidance behavior. The prevalence of vitamin D insufficiency (serum 25(OH)D3; 12 ng/mL (30 nmol/L) ≤ and <20 ng/mL (50 nmol/L))/deficiency (<12 ng/mL) was 47.7% in summer and 82.2% in winter. UV exposure time was short in Kumamoto (the urban area), at 11.6 min in summer and 14.9 min in winter. In Hokkaido (the rural area), UV exposure time was 58.3 min in summer and 22.5 min in winter. Vitamin D intake was significantly associated with serum 25(OH)D3, and a 1 μg/1000kcal increase in intake was necessary to increase 25(OH)D3 by 0.88 ng/mL in summer and by 1.7 ng/mL in winter. UV exposure time was significantly associated with serum 25(OH)D3 in summer, and a 10 min increase in UV exposure time was necessary to increase 25(OH)D3 by 0.47 ng/mL. Although consideration of personal occupation and lifestyle is necessary, most Japanese may need to increase both vitamin D intake and UV exposure.
New records of Convolvulaceae species for the Ceará state and its potential geographic distribution in Northeast Brazil

This study reports six new records of Convolvulaceae for Ceara state, notheastern Brazil: Ipomoea aristolochifolia G.Don, Ipomoea calyptrata Dammer, I. cynanchifolia Meisn, I. longibracteolata Sim. -Bianch. & J. R. I. Wood, I. meyeri G. Don and Jacquemontia mucronifera (Choisy) Hallier f. Of these, I. longibracteolata and I. meyeri are new records for the Atlantic Forest and Caatinga, respectively. For each species registered are provided descriptions, taxonomic and ecological comments, illustrations or photos of diagnostic characters and an ecological niche modeling analysis in northeast Brazil.
Amount of Brain Edema Correlates With Neurologic Recovery in Pediatric Cerebral Malaria

Supplemental Digital Content is available in the text. Background: Cerebral malaria (CM) remains a leading cause of mortality and morbidity in children in sub-Saharan Africa. Recent studies using brain magnetic resonance imaging have revealed increased brain volume as a major predictor of death. Similar morphometric predictors of morbidity at discharge are lacking. The aim of this study was to investigate the utility of serial cranial cisternal cerebrospinal fluid (CSF) volume measurements in predicting morbidity at discharge in pediatric CM survivors. Methods: In this case–control study, 54 Malawian pediatric CM survivors with neurologic sequelae evident at discharge who underwent serial magnetic resonance imaging scans while comatose were matched to concurrently admitted children with serial imaging who made full recoveries. Serial cranial cisternal CSF volume quantified by radiologists blinded to outcome was evaluated as a predictor of neurologic deficits at discharge. The probability of neurologic sequelae was determined using a model that included coma duration and changes in cisternal CSF volume over time. Results: Coma duration before admission was similar between cases and controls (16.1 vs. 15.3; P = 0.81), but overall coma was longer among children with sequelae (60 vs. 38 hours; P < 0.01). Lower initial CSF volumes and decreased volumes over time were both associated with a higher probability of neurologic sequelae at discharge. Conclusions: Among pediatric CM survivors with prolonged coma, lower initial CSF volume and decreasing volume during coma is associated with neurologic sequelae at discharge. These findings suggest that cerebral edema is an underlying contributor to both morbidity and mortality in pediatric CM.
Preparation, Characterization, and Evaluation of Cisplatin-Loaded Polybutylcyanoacrylate Nanoparticles with Improved In Vitro and In Vivo Anticancer Activities

This study aimed to evaluate the therapeutic efficacy of the cisplatin encapsulated into polybutylcyanoacrylate (PBCA) nanoparticles for the treatment of kidney cancer. The nanoformulation was successfully developed using the miniemulsion polymerization method and characterized in terms of size, size distribution, drug loading and encapsulation efficiencies, drug release behavior, in vitro cytotoxicity effects, in vivo toxicity, and therapeutic effects. Cisplatin-loaded PBCA nanoparticles were confirmed to be in nanoscale with the drug entrapment efficiency of 23% and controlled drug release profile, in which only 9% of the loaded drug was released after 48 h. The nanoparticles caused an increase in the cytotoxicity effects of cisplatin against renal cell adenocarcinoma cells (ACHN) (2.3-fold) and considerably decreased blood urea nitrogen and creatinine concentrations when compared to the standard cisplatin (1.6-fold and 1.5-fold, respectively). The nanoformulation also caused an increase in the therapeutic effects of cisplatin by 1.8-fold, in which a reduction in the mean tumor size was seen (3.5 mm vs. 6.5 mm) when compared to the standard cisplatin receiver rats. Overall, cisplatin-loaded PBCA nanoparticles can be considered as a promising drug candidate for the treatment of kidney cancer due to its potency to reduce the side effects of cisplatin and its toxicity and therapeutic effects on cancer-bearing Wistar rats.
Diverse types of genomic evidence converge on alcohol use disorder risk genes

Background Alcohol use disorder (AUD) is one of the most common forms of substance use disorders with a strong contribution of genetic (50%–60%) and environmental factors. Genome-wide association studies (GWAS) have identified a number of AUD-associated variants, including those in alcohol metabolism genes. These genetic variants may modulate gene expression, making individuals more susceptible to AUD. A long-term alcohol consumption can also change the transcriptome patterns of subjects via epigenetic modulations. Methods To explore the interactive effect of genetic and epigenetic factors on AUD, we conducted a secondary analysis by integrating GWAS, CNV, brain transcriptome and DNA methylation data to unravel novel AUD-associated genes/variants. We applied the mega-analysis of OR (MegaOR) method to prioritise AUD candidate genes (AUDgenes). Results We identified a consensus set of 206 AUDgenes based on the multi-omics data. We demonstrated that these AUDgenes tend to interact with each other more frequent than chance expectation. Functional annotation analysis indicated that these AUDgenes were involved in substance dependence, synaptic transmission, glial cell proliferation and enriched in neuronal and liver cells. We obtained a multidimensional evidence that AUD is a polygenic disorder influenced by both genetic and epigenetic factors as well as the interaction of them. Conclusion We characterised multidimensional evidence of genetic, epigenetic and transcriptomic data in AUD. We found that 206 AUD associated genes were highly expressed in liver, brain cerebellum, frontal cortex, hippocampus and pituitary. Our studies provides important insights into the molecular mechanism of AUD and potential target genes for AUD treatment.
An Effective Knowledge Transfer Approach for Multiobjective Multitasking Optimization

Multiobjective multitasking optimization (MTO), which is an emerging research topic in the field of evolutionary computation, was recently proposed. MTO aims to solve related multiobjective optimization problems at the same time via evolutionary algorithms. The key to MTO is the knowledge transfer based on sharing solutions across tasks. Notably, positive knowledge transfer has been shown to facilitate superior performance characteristics. However, how to find more valuable transferred solutions for the positive transfer has been scarcely explored. Keeping this in mind, we propose a new algorithm to solve MTO problems. In this article, if a transferred solution is nondominated in its target task, the transfer is positive transfer. Furthermore, neighbors of this positive-transfer solution will be selected as the transferred solutions in the next generation, since they are more likely to achieve the positive transfer. Numerical studies have been conducted on benchmark problems of MTO to verify the effectiveness of the proposed approach. Experimental results indicate that our proposed framework achieves competitive results compared with the state-of-the-art MTO frameworks.
Mental health challenges in academia: comparison between students of the various educational levels in Ghana

Abstract Background Students continue to face significant mental health challenges that vary in severity and type. It is, therefore, imperative that researchers and clinicians pay more attention to efforts aimed at improving the mental well-being of students. Aims This study examined the differences between Ghanaian students of the various educational levels on some mental health variables and the psychosocial factors of suicidal ideation. Methods Three hundred and fifty-seven (357) participants consisting of junior (92 students) and senior (99 students) high school students, undergraduates (86 students) and postgraduates (80 students) were involved in this cross-sectional study. Results The study revealed that high school students had higher academic stress, depression and suicidal ideation and they used more coping strategies compared to university students. Depression, age, and educational levels were the factors that facilitated suicidal ideation, with spiritual and ritual centred coping strategy and religion (Islam) serving as a buffer for suicidal ideation among students. These factors varied with different educational levels. Conclusions High school students experienced significant mental health problems compared to university students—this has direct implications on their academic and psychosocial development. The study recommends that mental health facilities be provided and managed by professionals, especially in high schools.
A novel mouse model of glucagon‐like peptide‐1 receptor expression: A look at the brain

Glucagon‐like peptide‐1 (GLP‐1) is an incretin hormone with a number of functions to maintain energy homeostasis and contribute to motivated behavior, both peripherally and within the central nervous system (CNS). These functions, which include insulin secretion, gastric emptying, satiety, and the hedonic aspects of food and drug intake, are primarily mediated through stimulation of the GLP‐1 receptor. While this receptor plays an important role in a variety of physiological outcomes, data regarding its CNS expression has been primarily limited to regional receptor binding and single‐label transcript expression studies. We thus developed a bacterial artificial chromosome transgenic mouse, in which expression of a red fluorescent protein (mApple) is driven by the GLP‐1R promoter. Using this reporter mouse, we characterized the regional and cellular expression patterns of GLP‐1R expressing cells in the CNS, using double‐label immunohistochemistry and in situ hybridization. GLP‐1R‐expressing cells were enriched in several key brain regions and circuits, including the lateral septum, hypothalamus, amygdala, bed nucleus of the stria terminalis, hippocampus, ventral midbrain, periaqueductal gray, and cerebral cortex. In most regions, GLP‐1R primarily colocalized with GABAergic neurons, except within some regions such as the hippocampus, where it was co‐expressed in glutamatergic neurons. GLP‐1R‐mApple cells were highly co‐expressed with 5‐HT3 receptor‐containing neurons within the cortex and striatum, as well as with dopamine receptor‐ and calbindin‐expressing cells within the lateral septum, the brain region in which GLP‐1R is most highly expressed. In this manuscript, we provide detailed images of GLP‐1R‐mApple expression and distribution within the brain and characterization of these neurons.
The Relation between Eating Habits and Abdominal Fat, Anthropometry, PON1 and IL-6 Levels in Patients with Multiple Sclerosis

Background: Multiple sclerosis (MS) is a chronic neurodegenerative disease of an inflammatory, demyelinating and autoimmune nature. Diets with a high caloric density could be especially relevant in terms of the pathogenesis related to an increase in adipose tissue that is metabolically active and releases mediators, which can induce systemic inflammation and an increased oxidation state. The aim of this study was to analyse the eating habits related to calorie intake and their impact on abdominal obesity associated with anthropometric variables, the activity of the oxidation marker paraoxonase 1 (PON1), and interleukin 6 (IL-6) levelsin MS patients. Methods: An analytical and quantitative observational study was conducted with a population of 57 MS patients. The dietary-nutritional anamnesis was gained through the Food Frequency Questionnaire and a food diary. Diet and eating habits have been analysed through the Easy Diet–Programa de gestión de la consulta® software. Anthropometric measurements were taken in order to determine the presence of abdominal obesity. In addition, PON1 was quantified in serum by means of automated spectrophotometric assays and IL-6 was quantified using the ELISA technique. Results: A normal calorie intake was determined for women, yet a slightly lower intake was observed in men. Carbohydrate consumption was below what was established, and protein and lipids were over, in both cases. Furthermore, most patients had abdominal obesity, with significantly higher body mass index (BMI), waist-to-hip ratio (WHR), waist-to-height ratio (WHtR), fat percentage and IL-6 levels. IL-6 is greatly correlated with waist circumference and WHtR. Conclusion: MS patients’ nutrient intake shows an imbalance between macronutrients. This seems to favour the abdominal obesity associated with high values of proinflammatory IL-6 that is not correlated with a lower activity of PON1.
Ecosystem size predicts the probability of speciation in migratory freshwater fish

Predicting speciation is a fundamental goal of research in evolutionary ecology. The probability of speciation is often positively correlated with ecosystem size. Although the mechanisms driving this correlation are generally difficult to identify, a shared geographical and ecological context provides a suitable condition to study the mechanisms that promote speciation in large ecosystems by reducing the number of factors to be considered. Here, we determined the correlation between speciation and ecosystem size, and discuss the underlying mechanisms of this relationship, using a probable parallel ecotype formation for freshwater fish. Our population genetic analysis revealed that speciation of the landlocked goby, Rhinogobius sp. YB, of the Ryukyu Archipelago, Japan, from its migratory ancestor, R. brunneus, occurred in parallel across five islands. Logistic regression analysis showed that speciation probability could be predicted using island size. The results suggest that ecosystem size predicts the occurrence of adaptation and reproductive isolation, probably through its association with three possible factors: divergent selection strength, population persistence, and occurrence probability of habitat separation.