Miracle-dz/UniFAR-FTUs huggingface dataset:
Rearing of Hermetia Illucens on Different Organic By-Products: Influence on Growth, Waste Reduction, and Environmental Impact

Simple Summary In the last few years great efforts have been made to find alternative protein sources to soybean meal and valorize organic by-product, which are produced in large amounts by food industries and are often inedible by humans. In this context, insects could be an alternative protein source. The aims of this study were to evaluate the growth performance, nutrient composition, and environmental impact of Hermetia illucens reared on a control hen diet and by-products diets (okara, maize distillers, and brewer’s grains). The rearing substrate affected larvae growth performance, nutritive value, and environmental impacts. Larvae fed on a hen diet and the maize distiller exhibited the higher final weight and required fewer days to reach the prepupal stage. The lipid content of the larvae was positively correlated to that of the insect diets. The environmental impact of larvae production on the hen diet, characterized by a high inclusion of soybean meal, was the most impactful for most of the environmental categories. Feed production activities were the main contributor to environmental impact. The use of by-products for larvae growth allowed us to reduce the environmental impact to produce 1 kg of protein in comparison with the use of soybean meal as a protein source. Abstract The aim of the study was to evaluate the use of three by-products as growing substrates for Hermetia illucens (Black Soldier Fly (BSF)) larvae: okara, maize distiller, brewer’s grains, and a control hen diet. The study focused on larval growth and bioconversion performance, production of methane by larvae and environmental burden of larvae production, using Life Cycle Assessment (LCA) on a lab scale. Chemical composition of substrates differed: okara had the highest crude protein and ether extract contents, while brewer’s grains showed the highest fiber content. Larvae fed on a hen diet and maize distiller exhibited the highest final weights (2.29 and 1.97 g, respectively). Larvae grown on okara showed the highest indexes for waste reduction and efficiency of conversion of the ingested feed. The BSF larvae did not produce any detectable traces of CH4. LCA evaluation showed that larvae production on a hen diet resulted in the most impact for most of environmental categories, for the inclusion of soybean meal in the diet (for climate change, 5.79 kg CO2 eq/kg dry larvae). Feed production activities resulted in the main contributions to environmental impact. In order to compare the larvae production obtained on all substrates, an environmental impact was attributed to okara and brewer’s grain through a substitution method, and, by this approach, the best sustainable product resulted from the larvae grown on the maize distiller.
Scribble, Erbin, and Lano redundantly regulate epithelial polarity and apical adhesion complex

Epithelial apicobasal polarity in Drosophila depends on the basolateral protein Scribble (Scrib), but the role of mammalian Scrib is unclear. Choi et al. now report that mammalian Scrib also mediates epithelial apicobasal polarity but this function is obscured by compensatory activity of other LAP proteins, Erbin and Lano.
A Novel Ensemble Artificial Intelligence Approach for Gully Erosion Mapping in a Semi-Arid Watershed (Iran)

In this study, we introduced a novel hybrid artificial intelligence approach of rotation forest (RF) as a Meta/ensemble classifier based on alternating decision tree (ADTree) as a base classifier called RF-ADTree in order to spatially predict gully erosion at Klocheh watershed of Kurdistan province, Iran. A total of 915 gully erosion locations along with 22 gully conditioning factors were used to construct a database. Some soft computing benchmark models (SCBM) including the ADTree, the Support Vector Machine by two kernel functions such as Polynomial and Radial Base Function (SVM-Polynomial and SVM-RBF), the Logistic Regression (LR), and the Naïve Bayes Multinomial Updatable (NBMU) models were used for comparison of the designed model. Results indicated that 19 conditioning factors were effective among which distance to river, geomorphology, land use, hydrological group, lithology and slope angle were the most remarkable factors for gully modeling process. Additionally, results of modeling concluded the RF-ADTree ensemble model could significantly improve (area under the curve (AUC) = 0.906) the prediction accuracy of the ADTree model (AUC = 0.882). The new proposed model had also the highest performance (AUC = 0.913) in comparison to the SVM-Polynomial model (AUC = 0.879), the SVM-RBF model (AUC = 0.867), the LR model (AUC = 0.75), the ADTree model (AUC = 0.861) and the NBMU model (AUC = 0.811).
False Discovery Rate Control in Cancer Biomarker Selection Using Knockoffs

The discovery of biomarkers that are informative for cancer risk assessment, diagnosis, prognosis and treatment predictions is crucial. Recent advances in high-throughput genomics make it plausible to select biomarkers from the vast number of human genes in an unbiased manner. Yet, control of false discoveries is challenging given the large number of genes versus the relatively small number of patients in a typical cancer study. To ensure that most of the discoveries are true, we employ a knockoff procedure to control false discoveries. Our method is general and flexible, accommodating arbitrary covariate distributions, linear and nonlinear associations, and survival models. In simulations, our method compares favorably to the alternatives; its utility of identifying important genes in real clinical applications is demonstrated by the identification of seven genes associated with Breslow thickness in skin cutaneous melanoma patients.
Modulation Effects of Cordycepin on Voltage-Gated Sodium Channels in Rat Hippocampal CA1 Pyramidal Neurons in the Presence/Absence of Oxygen

Our previous study revealed that cordycepin features important neuroprotective effects against hypoxic insult by improvement of neuronal electrophysiological function. Modulation on voltage-gated sodium channel (VGSC) in CA1 neurons is the initial event during hypoxia/ischemia. However, no study comprehensively investigated cordycepin on VGSC. Hence, this study investigated modulation effects of cordycepin on VGSC not only in oxygen physiological conditions but also in acute oxygen deprivation injury conditions. Results revealed that cordycepin (80 μM) reduced the amplitude of VGSC currents (INa) (77.6% of control, p < 0.01) within 1 min of drug exposure coupled with a negative shift in steady-state inactivation and prolonged recovery time course from inactivation. Additionally, this mild reduction on the peak of INa induced by the pretreatment with cordycepin can attenuate and delay the following hypoxia causing rapid dramatic decrease in INa with no additive change in the voltage dependence of inactivation. As modulation on VGSC in CA1 neurons represents the initial event during ischemia, we propose that suppression effect of cordycepin on VGSC is an important neuronal protective mechanism that may enhance neuronal tolerance to acute oxygen deprivation and delay hypoxia-induced neuronal injuries.
Persistent opioid use is associated with worse survival after lobectomy for stage i non-small cell lung cancer.

The incidence of persistent opioid use after lung surgery is high. Although adverse effects by opioids have been well described, it is unknown whether persistent opioid use is associated with worse survival.Patients who received a lobectomy for stage I NSCLC from 2007 - 2013 were identified from the SEER-Medicare database. Opioid use was ascertained through records of prescriptions filled through Part D. Patients were matched 2:1 according to their likelihood of persistent opioid use, which was defined as any opioid prescription filled 3-6 months after surgery.2,884 patients were identified. The incidence of persistent opioid use 3-6 months after surgery was 27.0%. After matching, persistent opioid use was associated with worse overall survival (p<0.001) and cancer-specific survival (p<0.001). Those who used the lowest quartile of opioids, which was often manifested as a single opioid prescription, showed similar overall survival as no opioid use (HR 1.27, 95% CI 0.93 - 1.72). However, the second and third quartile of opioid use were associated with decreased overall survival (HR 1.53, 95% CI 1.14 - 2.03 and HR 1.39, 95% CI 1.04 - 1.86, respectively) that was nonetheless less severe than the highest quartile of opioid use (HR 2.50, 95% CI 1.95 - 3.21). Age, sex, marital status, comorbidity, tumor size, tumor grade and radiation were also associated with worse overall survival, with chemotherapy use and VATS being associated with improved overall survival.Persistent opioid use 3 to 6 months after lobectomy is independently associated with worse overall survival and worse cancer-specific survival.
Influence of flavivirus co-circulation in serological diagnostics and surveillance: a model of study using West Nile, Usutu and Bagaza viruses.

This study aims at assessing the serological cross-reactions existing between three mosquito-borne flaviviruses with avian reservoirs co-circulating in Europe: West Nile (WNV), Usutu (USUV) and Bagaza (BAGV). The study is useful for a better interpretation of serological results in diagnostics and surveillance. Serum samples obtained from a natural host, the red-legged partridge (Alectoris rufa), experimentally infected with WNV, USUV or BAGV were analysed using two commercially available WNV competition ELISAs suitable for serological surveillance, and by the confirmatory virus neutralization test (VNT). The ELISAs examined showed different levels of specificity for WNV, as judged by cross-reaction observed with the other flaviviruses. By VNT, virus-specific antibodies were confirmed in 80%, 50% or 0% of sera from WNV-, BAGV-, or USUV-inoculated birds, respectively. The results indicate how the co-circulation of cross-reacting flaviviruses may affect the outcomes of WNV serological surveillance when applying currently available serological tools. On the one hand, the choice of the ELISA test for antibody screening should consider the differences found in specificity, since one test is more specific for WNV while the other one is more suitable for detection of a broader range of flavivirus antibodies. On the other hand, besides corroborating that cross-neutralization occurs between flaviviruses from different serocomplexes (WNV/USUV and BAGV), this study points out that cross-neutralization between WNV and USUV is not symmetric, and reveals the difficulty to identify USUV infections serologically. This finding indicates that actual USUV infections might be underestimated in the current diagnostic schemes. This article is protected by copyright. All rights reserved.
Heterogeneous Dielectric Implicit Membrane Model for the Calculation of MMPBSA Binding Free Energies

Membrane-bound protein receptors are a primary biological drug target, but the computational analysis of membrane proteins has been limited. In order to improve molecular mechanics Poisson-Boltzmann surface area (MMPBSA) binding free energy calculations for membrane protein-ligand systems, we have optimized a new heterogeneous dielectric implicit membrane model, with respect to free energy simulations in explicit membrane and explicit water, and implemented it into the Amber software suite. This new model supersedes our previous uniform, single dielectric implicit membrane model by allowing the dielectric constant to vary with depth within the membrane. We calculated MMPBSA binding free energies for the human purinergic platelet receptor (P2Y12R) and two of the muscarinic acetylcholine receptors (M2R and M3R) bound to various antagonist ligands using both membrane models, and we found that the heterogeneous dielectric membrane model has a stronger correlation with experimental binding affinities compared to the older model under otherwise identical conditions. This improved membrane model increases the utility of MMPBSA calculations for the rational design and improvement of future drug candidates.
Latina Mothers Caring for a Son or Daughter With Autism or Schizophrenia: Similarities, Differences, and the Relationship Between Co-Residency and Maternal Well-Being

In this cross-sectional study, the authors examined similarities and differences in depressive symptoms and psychological well-being between Latina maternal caregivers of persons with autism (n = 29) and schizophrenia (n = 33). They also explored predictors of maternal outcomes and the relationship of co-residence to them. Regression analysis found that mothers of adults with schizophrenia had lower levels of psychological well-being than mothers of youth or adults with autism. For the overall sample of mothers, co-residing with their son or daughter was significantly related to lower levels of depressive symptoms. Qualitative analysis of the nine mothers who lived apart from their son or daughter revealed that extreme behavior problems of the son or daughter and poor maternal health contributed to living apart. Despite overcoming these challenges, mothers expressed a profound sense of sadness about their sons' or daughters' living arrangements.
Proton therapy for non-squamous cell carcinoma of the head and neck: planning comparison and toxicity

Abstract To investigate optimal treatment planning using proton beams for non-squamous cell carcinoma of the head and neck (NSCHN), the dose distributions of plans involving pencil beam scanning (PBS) with or without a patient-specific aperture system (PSAS), passive-scattering proton therapy (PSPT) and X-ray intensity-modulated radiotherapy (IMRT) were compared. As clinical results, toxicities of PBS with PSAS, including changes in quality of life, were reported. Between April 2014 and August 2016, a total of 30 patients were treated using PBS with PSAS. In 20 patients selected at random, the dose distributions of PBS with or without the PSAS, PSPT and IMRT plans were compared. Neutron exposure by proton therapy was calculated using a Monte Carlo simulation. Toxicities were scored according to CTCAE ver. 4.0. Patients completed EORTC quality of life survey forms (QLQ-C30 and QLQ-HN35) before and 0–12 months after proton therapy. The 95% conformity number of PBS with the PSAS plan was the best, and significant differences were detected among the four plans (P < 0.05, Bonferroni tests). Neutron generation by PSAS was ~1.1-fold higher, but was within an acceptable level. No grade 3 or higher acute dermatitis was observed. Pain, appetite loss and increased weight loss were more likely at the end of treatment, but recovered by the 3 month follow-up and returned to the pretreatment level at the 12 month follow-up. PBS with PSAS reduced the penumbra and improved dose conformity in the planning target volume. PBS with PSAS was tolerated well for NSCHN.
Structure of the super-elongation complex subunit AFF4 C-terminal homology domain reveals requirements for AFF homo- and heterodimerization

AF4/FMR2 family member 4 (AFF4) is the scaffold protein of the multisubunit super-elongation complex, which plays key roles in the release of RNA polymerase II from promoter-proximal pausing and in the transactivation of HIV-1 transcription. AFF4 consists of an intrinsically disordered N-terminal region that interacts with other super-elongation complex subunits and a C-terminal homology domain (CHD) that is conserved among AF4/FMR2 family proteins, including AFF1, AFF2, AFF3, and AFF4. Here, we solved the X-ray crystal structure of the CHD in human AFF4 (AFF4-CHD) to 2.2 Å resolution and characterized its biochemical properties. The structure disclosed that AFF4-CHD folds into a novel domain that consists of eight helices and is distantly related to tetratrico peptide repeat motifs. Our analyses further revealed that AFF4-CHD mediates the formation of an AFF4 homodimer or an AFF1-AFF4 heterodimer. Results from fluorescence anisotropy experiments suggested that AFF4-CHD interacts with both RNA and DNA in vitro. Furthermore, we identified a surface loop region in AFF4-CHD as a substrate for the P-TEFb kinase cyclin-dependent kinase 9, which triggers release of polymerase II from promoter-proximal pausing sites. In conclusion, the AFF-CHD structure and biochemical analyses reported here reveal the molecular basis for the homo- and heterodimerization of AFF proteins and implicate the AFF4-CHD in nucleic acid interactions. The high conservation of the CHD among several other proteins suggests that our results are also relevant for understanding other CHD-containing proteins and their dimerization behavior.
Integration of prognostics at a system level: a Petri net approach

This paper presents a mathematical framework for modeling prognostics at a system level, by combining the prognostics principles with the Plausible Petri nets (PPNs) formalism, first developed in M. Chiachío et al. [Proceedings of the Future Technologies Conference, San Francisco, (2016), pp. 165-172]. The main feature of the resulting framework resides in its efficiency to jointly consider the dynamics of discrete events, like maintenance actions, together with multiple sources of uncertain information about the system state like the probability distribution of end-of-life, information from sensors, and information coming from expert knowledge. In addition, the proposed methodology allows us to rigorously model the flow of information through logic operations, thus making it useful for nonlinear control, Bayesian updating, and decision making. A degradation process of an engineering sub-system is analyzed as an example of application using condition-based monitoring from sensors, predicted states from prognostics algorithms, along with information coming from expert knowledge. The numerical results reveal how theinformation from sensors and prognostics algorithms can be processed, transferred, stored, and integrated with discreteevent maintenance activities for nonlinear control operations at system level.
Obesity as an Inflammatory Agent Can Cause Cellular Changes in Human Milk due to the Actions of the Adipokines Leptin and Adiponectin

Adiponectin and leptin play roles in the hunger response, and they can induce the inflammatory process as the initial mechanism of the innate immune response. It is possible for alterations in the levels of these adipokines to compromise the functional activity of human colostrum phagocytes. Therefore, the objective of this study is to analyze the effects of adiponectin and leptin on colostrum mononuclear (MN) cells. Colostrum was collected from 80 healthy donors, who were divided into two groups: the control group and the high body mass index (BMI) group. MN cells were used to analyze phagocytosis by flow cytometry, and reactive oxygen species (ROS), intracellular calcium, and apoptosis were assessed by fluorimetry using a microplate reader. Adipokines restored the levels of phagocytosis to the high BMI group (p < 0.05), with a mechanism that is action-dependent on the release of ROS and intracellular calcium. However, adiponectin and leptin simultaneously contributed to better microbicidal activity, thus reflecting an increase in the apoptosis level (p < 0.05) in the high BMI group. Probably, the maintenance of the balance between adiponectin and leptin levels enhances the protection and decreases the indices of neonatal infection in the breastfeeding infants of women with high BMI values. Therefore, policies that support pre-gestational weight control should be encouraged.
The rise of circulatory endothelin (ET)-1 and endothelin receptors (ETA, ETB) expression in kidney of obese wistar rat.

BACKGROUND Endothelin (ET)-1, a circulatory protein, and its receptors (ETA and ETB) in various organs were reported to play a pivotal role in many diseases, including obesity. However, the changes of ETA and ETB expression in ventricle and kidney in obesity was less reported. The study is designed to observe the level of circulatory ET-1 and expression of ETA/ETB in ventricle and kidney of obese, as compared to non-obese, Wistar rats. METHODS Groups of obese 14 and 34 weeks Wistar rats were compared to non-obese controls at similar ages. The obesity status was achieved by feeding the with high calories protein diet CP 551 + milk powder, while the control group was fed with a standard calorie protein AD II diet. The concentration of circulatory ET-1, ETA and ETB of ventricle and kidney were measured by Enzyme Linked Immunosorbent Assay (ELISA) technique after the termination of both groups at 14th and 24th weeks. RESULTS The level of circulatory ET-1, expression of ETA and ETB in kidney, and LDL of obese rats were significantly higher than control rats (T-Test, P<0.05) in the elder groups, while no differences of the ETA and ETB were found in the ventricle. No differences of the levels of circulatory ET-1, ETA and ETB expression were found between obese and control groups of younger rats (P>0.05). HDL levels were under normal value for both groups. CONCLUSION Obesity in elder obese rats leads to dysregulation of kidney vessels through activity of ET-1 and ETA/ETB.
Pharmacotherapeutic strategies for managing comorbid depression and diabetes

ABSTRACT Introduction: The increasing prevalence of comorbid depression and diabetes exerts a heavy burden on global health. Co-occurrence of depression and diabetes is common, affecting 14% to 35.8% of patients with diabetes, leading to a higher mortality and morbidity rate, more micro- and macro-vascular diseases and more cognitive decline. Areas covered: In this paper, the authors address various areas from epidemiology, the association between depression and diabetes, treatment strategies and future directions based on the currently available literature to provide novel insight into the pharmacotherapeutic management of comorbid depression and diabetes. Expert opinion: Pharmacotherapy can help patients with comorbid depression and diabetes by relieving depressive symptoms and improving glycemic control. When combined with psychological therapy, as a collaborative care effort, pharmacological therapy based on selective serotonin reuptake inhibitors (SSRIs) is recommended for comorbid depression with diabetes. Furthermore, studies with larger sample sizes that can help to define different subtypes of diabetes and severity of depression are needed so that clinicians can draw up a precise and applicable management guidelines for the personalized therapy of these diseases.
Insights into resistance mechanism of hepatitis C virus nonstructural 3/4A protease mutant to boceprevir using umbrella sampling simulation study

Abstract Hepatitis C virus can cause inflammation in human liver cells, leading to liver cirrhosis and liver cancer. Based on the World Health Organization reports, about 228 million people in the world have hepatitis C. To date, some inhibitory medicines against the hepatitis C virus nonstructural 3/4A protease, such as boceprevir, have entered clinical trial phases. However, several hepatitis C virus nonstructural 3/4A protease mutations have been recognized to decrease susceptibility of boceprevir to hepatitis C virus. The molecular details behind inhibitor resistance of these single-point mutations are not still understood. Thus, in this research, computational strategies were applied to clarify the inhibitor resistance mechanism. From umbrella sampling simulation and energy profiles, the polar interactions are the main driving force for boceprevir binding. Based on the analyzed R155T mutant, the main reason for the occurrence of boceprevir resistance is the conformation alterations of S4 and extended S2 binding pockets. These changes, lead to decreased binding ability of the key residues to P2 and P4 moieties of boceprevir. Moreover, structural results show that the disappearance of important salt bridges can bring about the great conformation changes of the binding pockets in R155T. Communicated by Ramaswamy H. Sarma