Miracle-dz/UniFAR-FTUs huggingface dataset:
A recurrent neural network framework for flexible and adaptive decision making based on sequence learning

The brain makes flexible and adaptive responses in a complicated and ever-changing environment for an organism’s survival. To achieve this, the brain needs to understand the contingencies between its sensory inputs, actions, and rewards. This is analogous to the statistical inference that has been extensively studied in the natural language processing field, where recent developments of recurrent neural networks have found many successes. We wonder whether these neural networks, the gated recurrent unit (GRU) networks in particular, reflect how the brain solves the contingency problem. Therefore, we build a GRU network framework inspired by the statistical learning approach of NLP and test it with four exemplar behavior tasks previously used in empirical studies. The network models are trained to predict future events based on past events, both comprising sensory, action, and reward events. We show the networks can successfully reproduce animal and human behavior. The networks generalize the training, perform Bayesian inference in novel conditions, and adapt their choices when event contingencies vary. Importantly, units in the network encode task variables and exhibit activity patterns that match previous neurophysiology findings. Our results suggest that the neural network approach based on statistical sequence learning may reflect the brain’s computational principle underlying flexible and adaptive behaviors and serve as a useful approach to understand the brain.
HLA and AB0 Polymorphisms May Influence SARS-CoV-2 Infection and COVID-19 Severity.

BACKGROUND SARS-CoV-2 infection is heterogeneous in clinical presentation and disease evolution. To investigate whether immune response to the virus can be influenced by genetic factors, we compared HLA and AB0 frequencies in organ transplant recipients and waitlisted patients according to presence or absence of SARS-CoV-2 infection. METHODS A retrospective analysis was performed on an Italian cohort composed by transplanted and waitlisted patients in a January 2002-March 2020 time frame. Data from this cohort were merged with the Italian registry of COVID subjects, evaluating infection status of transplanted and waitlisted patients. A total of 56304 cases were studied with the aim of comparing HLA and AB0 frequencies according to the presence (n=265, COVID) or absence (n=56 039, COVID) of SARS-CoV-2 infection. RESULTS The cumulative incidence rate of COVID-19 was 0.112% in the Italian population and 0.462% in waitlisted/transplanted patients (OR=4.2, 95%CI [3.7-4.7], P<0.0001). HLA-DRB1*08 was more frequent in COVID (9.7% and 5.2%: OR=1.9, 95%CI [1.2-3.1]; P=0.003; Pc=0.036). In COVID patients, HLA-DRB1*08 was correlated to mortality (6.9% in living vs 17.5% in deceased: OR=2.9, 95%CI [1.15-7.21]; P=0.023). Peptide binding prediction analyses showed that these DRB1*08 alleles were unable to bind any of the viral peptides with high affinity. Lastly, blood group A was more frequent in COVID (45.5%) than COVID patients (39.0%; OR=1.3, 95%CI [1.02-1.66]; P=0.03). CONCLUSIONS Even though preliminary, these results suggest that HLA antigens may influence SARS-CoV-2 infection and clinical evolution of COVID-19 and confirm that blood group A individuals are at greater risk of infection, providing clues on the spread of the disease and indications about infection prognosis and vaccination strategies.
Ultrafine and High-Strength Silk Fibers Secreted by Bimolter Silkworms

Ultrafine fibers are widely employed because of their lightness, softness, and warmth retention. Although silkworm silk is one of the most applied natural silks, it is coarse and difficult to transform into ultrafine fibers. Thus, to obtain ultrafine high-performance silk fibers, we employed anti-juvenile hormones in this study to induce bimolter silkworms. We found that the bimolter cocoons were composed of densely packed thin fibers and small apertures, wherein the silk diameter was 54.9% less than that of trimolter silk. Further analysis revealed that the bimolter silk was cleaner and lighter than the control silk. In addition, it was stronger (739 MPa versus 497 MPa) and more stiffness (i.e., a higher Young’s modulus) than the trimolter silk. FTIR and X-ray diffraction results revealed that the excellent mechanical properties of bimolter silk can be attributed to the higher β-sheet content and crystallinity. Chitin staining of the anterior silk gland suggested that the lumen is narrower in bimolters, which may lead to the formation of greater numbers of β-sheet structures in the silk. Therefore, this study reveals the relationship between the structures and mechanical properties of bimolter silk and provides a valuable reference for producing high-strength and ultrafine silk fibers.
Biochemical activity of plants of the genus Alternanthera after UV-C radiation exposure.

UV-C radiation interferes with the physiological processes of plants. The increment of secondary metabolites, such as flavonoids and betalains as well as enzymatic activities, can explain the behavior of plants exposed to radiation. The objective of this study was to analyze the possible changes in the metabolism of plants of Alternanthera sessilis, Alternanthera brasiliana and Alternanthera philoxeroides, when exposed to different periods of UV-C radiation. Plants from in vitro culture were acclimatized in greenhouse for 60 days before they were exposed to UV-C radiation for 0, 5, 10, 15 and 20 minutes. Biochemical analyses of production of total betanidin, betanin, betaxanthins, flavonoids and the response of antioxidant enzymes as a result of exposure to UV-C radiation were carried out at the end of this study. The results showed that there was an increment of these secondary metabolism compounds in the species A. sessilis, and the maximum values were achieved after 10 and 12 minutes of exposure. The species A. brasiliana showed increased betanin content after 16 minutes of exposure. For the enzyme superoxide dismutase (SOD) there was no significant difference among the species in the different periods of exposure, for catalase (CAT), the species A. philoxeroides showed greater activity, differing significantly from the other species. Greater activity of ascorbate peroxidase (APX), for this species, at 20 minutes of UV-C radiation exposure was also found. Malondialdehyde (MDA) content increased in A. philoxeroides and A. sessilis, because of UV-C radiation. It follows that the species studied trigger different protection mechanisms in the face of UV-C radiation
High Dose Ifosfamide in Relapsed and Unresectable High-Grade Osteosarcoma Patients: A Retrospective Series

Background: The evidence on high-dose ifosfamide (HD-IFO) use in patients with relapsed osteosarcoma is limited. We performed a retrospective study to analyze HD-IFO activity. Methods: Patients with osteosarcoma relapsed after standard treatment [methotrexate, doxorubicin, cisplatin +/− ifosfamide (MAP+/−I)] with measurable disease according to RECIST1.1 were eligible to ifosfamide (3 g/m2/day) continuous infusion (c.i.) days 1–5 q21d. RECIST1.1 overall response rate (ORR) (complete response (CR) + partial response (PR)), progression-free survival at 6-month (6m-PFS), duration of response (DOR), and 2-year overall survival (2y-OS) were assessed. PARP1 expression and gene mutations were tested by immunohistochemistry and next-generation sequencing. Results: 51 patients were included. ORR was 20% (1 CR + 9 PR). Median DOR was 5 months (95%CI 2–7). Median PFS, 6m-PFS, OS, and 2y-OS were 6 months (95%CI 4–9), 51%, 15 months (10–19), and 30%, respectively. A second surgical complete remission (CR2) was achieved in 26 (51%) patients. After multivariate analysis, previous use of ifosfamide (HR 2.007, p = 0.034) and CR2 (HR 0.126, p < 0.001) showed a significant correlation with PFS and OS, respectively. No significant correlation was found between outcomes and PARP1 or gene mutations. Conclusions: HD-IFO should be considered as the standard first-line treatment option in relapsed osteosarcoma and control arm of future trial in this setting.
Ameliorative Effect of Graviola (Annona muricata) on Mono Sodium Glutamate-Induced Hepatic Injury in Rats: Antioxidant, Apoptotic, Anti-inflammatory, Lipogenesis Markers, and Histopathological Studies

Simple Summary Food additives, especially monosodium glutamate (MSG), induces serious liver disorders. This study premeditated to investigate the effect of Graviola extract (GE) on hepatic and cellular alterations induced by MSG. Our result revealed that GE administration normalized the oxidative stress markers, as well as the proinflammatory cytokines, in addition to downregulation of the inducible nitric oxide synthase (iNOS) and FAS, hepatic fatty acid synthase, and led to the upregulation of the silent information regulator protein one (SIRT1) gene. This is the first report investigating the intracellular pathway and mechanism of Graviola extract’s action in alleviating the MSG supplementation injuries. Abstract Monosodium glutamate (MSG) is a widely used food additive, and there is a trepidation that MSG plays a critical role in multiple hepatic disorders. This study was planned to investigate Graviola extract (GE) effects on hepatic and cellular alterations induced by MSG. Fifty Wistar rats were randomly allocated into five groups: control (received normal saline), Graviola (received 200 mg/kg body weight), MSG (received 2.4 gm MSG/kg, 15% of Lethal dose (LD50) of MSG), Graviola + monosodium glutamate (MSG + GE; received GE, 200 mg/kg/day and MSG 2.4 gm/kg body weight (BW) for the next four weeks), and monosodium glutamate + Graviola (received MSG only (2.4 gm/kg BW) daily for four weeks, then concomitant with Graviola (200 mg/kg BW) daily for the next four weeks. MSG and GR were administered orally for eight weeks. Our results showed that MSG caused a significant increase in oxidative stress markers malondialdehyde (MDA), reactive oxygen species (ROS), nitric oxide (NO), hydrogen peroxide (H2O2), proinflammatory cytokines interleukin 6 (IL-6) level, a tumor protein (P53), hepatic cellular damage, as well as proapoptotic markers caspase-3, and B-cell lymphoma 2 (BCL-2)-like protein 4 (Bax). A significant decrease in superoxide dismutase (SOD), catalase (CAT), glutathione S transferase (GST), reduced glutathione (GSH), and an antiapoptotic agent B-cell lymphoma 2 (BCl-2) was observed. The detected MSG effects were normalized by Graviola administration, either a prophylactic or protecting dose. Besides, Graviola reduced the expression of inducible nitric oxide synthase (iNOS) and hepatic fatty acid synthase (FAS) and led to the upregulation of the silent information regulator protein one gene expression gene (SIRT1). In conclusion, the results suggest that Gaviola’s interrelated antiapoptotic, antioxidant, and anti-inflammatory properties are potential mechanisms to enhance hepatic deficits and protect the liver. Graviola can, therefore, be considered a promising hepatoprotective supplement. Additionally, further human clinical trials are also necessary to validate the present research.
Polymeric Inserts Containing Eudragit® L100 Nanoparticle for Improved Ocular Delivery of Azithromycin

Polymeric inserts containing azithromycin-loaded Eudragit® L100 nanoparticles were developed to sustain the drug release and enhance its ocular performance. The solvent diffusion technique was employed to prepare nanoparticles. The developed nanoparticles (NPs) were fully characterized and investigated. The solvent casting method was used to prepare azithromycin ocular inserts (azithromycin, AZM film) by adding hydroxypropyl methylcellulose (HPMC) or hydroxyethyl cellulose (HEC) solutions after the incorporation of AZM-loaded Eudragit® L100 nanoparticles into plasticized PVA (polyvinyl alcohol) solutions. The optimized nanoparticles had a particle size of 78.06 ± 2.3 nm, zeta potential around −2.45 ± 0.69 mV, polydispersity index around 0.179 ± 0.007, and entrapment efficiency 62.167 ± 0.07%. The prepared inserts exhibited an antibacterial effect on Staphylococcus aureus and Escherichia coli cultures. The inserts containing AZM-loaded nanoparticles showed a burst release during the initial hours, followed by a sustained drug release pattern. Higher cumulative corneal permeations from AZM films were observed for the optimized formulation compared to the drug solution in the ex-vivo trans-corneal study. In comparison to the AZM solution, the inserts significantly prolonged the release of AZM in rabbit eyes (121 h). The mucoadhesive inserts containing azithromycin-loaded Eudragit® L100 nanoparticles offer a promising approach for the ocular delivery of azithromycin (antibacterial and anti-inflammatory) to treat ocular infections that require a prolonged drug delivery.
Age Differences in Sexual Minority Stress and the Importance of Friendship in Later Life

ABSTRACT Objectives This study examined whether younger and middle-aged and older sexual minorities (YSM, MAOSM) experience minority stress differently in relation to social support and depressive symptomatology. Methods Cross-sectional data from 238 sexual minorities (18–80; M = 40.93) comprised the sample, who were strategically separated into cohorts. Group difference and regression methods were used to examine differences in minority stress between groups and the relationships between minority stress-social support-depressive symptomatology within groups. Results MAOSM had greater outness and lower IH. Additionally, outness and IH were the best predictors for the MAOSM and YSM group, respectively. MAOSM indicated better adaption to minority stresses, highlighting the importance of friend support as a protective mechanism Conclusions The minority stress-depressive symptomatology is mitigated by friend support in MAOSM. Clinical Implications OSM and YSM demonstrate different susceptibility of minority stress on depressive symptomatology, with outness being a stronger indicator in MAOSM and IH being a stronger predictor in YSM. Social support does not work uniformly in different cohorts; however, multiple sources (i.e., family, friends) should be discussed with clients. Clinicians should treat cohort as one of the defining features of a sexual minority’s lifelong experience with minority stress.
Intracellular Metabolomics Switching Alters Extracellular Acid Production and Insoluble Phosphate Solubilization Behavior in Penicillium oxalicum

This research aims to understand the precise intracellular metabolic processes of how microbes solubilize insoluble phosphorus (Insol-P) to increase bio-available P. Newly isolated Penicillium oxalicum PSF-4 exhibited outstanding tricalcium phosphate (TP) and iron phosphate (IP) solubilization performance—as manifested by microbial growth and the secretion of low-molecular-weight organic acids (LMWOAs). Untargeted metabolomics approach was employed to assess the metabolic alterations of 73 intracellular metabolites induced by TP and IP compared with soluble KH2PO4 in P. oxalicum. Based on the changes of intracellular metabolites, it was concluded that (i) the enhanced intracellular glyoxylate and carbohydrate metabolisms increased the extracellular LMWOAs production; (ii) the exposure of Insol-P poses potential effects to P. oxalicum in destructing essential cellular functions, affecting microbial growth, and disrupting amino acid, lipid, and nucleotide metabolisms; and (iii) the intracellular amino acid utilization played a significant role to stimulate microbial growth and the extracellular LMWOAs biosynthesis.
A Novel FRET Approach Quantifies the Interaction Strength of Peroxisomal Targeting Signals and Their Receptor in Living Cells

Measuring Förster–resonance–energy–transfer (FRET) efficiency allows the investigation of protein–protein interactions (PPI), but extracting quantitative measures of affinity necessitates highly advanced technical equipment or isolated proteins. We demonstrate the validity of a recently suggested novel approach to quantitatively analyze FRET-based experiments in living mammalian cells using standard equipment using the interaction between different type-1 peroxisomal targeting signals (PTS1) and their soluble receptor peroxin 5 (PEX5) as a model system. Large data sets were obtained by flow cytometry coupled FRET measurements of cells expressing PTS1-tagged EGFP together with mCherry fused to the PTS1-binding domain of PEX5, and were subjected to a fitting algorithm extracting a quantitative measure of the interaction strength. This measure correlates with results obtained by in vitro techniques and a two-hybrid assay, but is unaffected by the distance between the fluorophores. Moreover, we introduce a live cell competition assay based on this approach, capable of depicting dose- and affinity-dependent modulation of the PPI. Using this system, we demonstrate the relevance of a sequence element next to the core tripeptide in PTS1 motifs for the interaction strength between PTS1 and PEX5, which is supported by a structure-based computational prediction of the binding energy indicating a direct involvement of this sequence in the interaction.
In Vitro Assessment of the Impact of Industrial Processes on the Gastrointestinal Digestion of Milk Protein Matrices Using the INFOGEST Protocol

The goal of this study was to determine the impact of industrial processes on the digestion of six milk protein matrices using the harmonized INFOGEST in vitro static digestion protocol. First, this method was optimized to simple protein matrices using sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and size exclusion chromatography (SEC) to compare the intestinal protein hydrolysis obtained with increasing quantities of pancreatin. Similar results were achieved with the originally required pancreatin amount (trypsin activity of 100 U.mL−1) and with a quantity of pancreatin equivalent to a trypsin activity of 27.3 U.mL−1, which was thus used to perform the in vitro digestion of the milk matrices. Molecular weight profiles, peptide heterogeneity from LC-MS/MS data, calcium, free amino acid, and peptide concentrations were determined in the gastric and intestinal phases to compare the milk protein digests. Results showed that the industrial process affected not only the protein distribution of the matrices but also most likely the protein structures. Indeed, differences arose in terms of peptide populations generated when the caseins were reticulated or when their calcium concentrations were reduced.
CancerGram: An Effective Classifier for Differentiating Anticancer from Antimicrobial Peptides

Antimicrobial peptides (AMPs) constitute a diverse group of bioactive molecules that provide multicellular organisms with protection against microorganisms, and microorganisms with weaponry for competition. Some AMPs can target cancer cells; thus, they are called anticancer peptides (ACPs). Due to their small size, positive charge, hydrophobicity and amphipathicity, AMPs and ACPs interact with negatively charged components of biological membranes. AMPs preferentially permeabilize microbial membranes, but ACPs additionally target mitochondrial and plasma membranes of cancer cells. The preference towards mitochondrial membranes is explained by their membrane potential, membrane composition resulting from α-proteobacterial origin and the fact that mitochondrial targeting signals could have evolved from AMPs. Taking into account the therapeutic potential of ACPs and millions of deaths due to cancer annually, it is of vital importance to find new cationic peptides that selectively destroy cancer cells. Therefore, to reduce the costs of experimental research, we have created a robust computational tool, CancerGram, that uses n-grams and random forests for predicting ACPs. Compared to other ACP classifiers, CancerGram is the first three-class model that effectively classifies peptides into: ACPs, AMPs and non-ACPs/non-AMPs, with AU1U amounting to 0.89 and a Kappa statistic of 0.65. CancerGram is available as a web server and R package on GitHub.
Antimicrobial and Immunomodulatory Effects of Bifidobacterium Strains: A Review

Bifidobacterium strains can provide several health benefits, such as antimicrobial and immunomodulatory effects. Some strains inhibit growth or cell adhesion of pathogenic bacteria, including multidrug-resistant bacteria, and their antibacterial activity can be intensified when combined with certain antibiotics. In addition, some strains of bifidobacteria reduce viral infectivity, leading to less epithelial damage of intestinal tissue, lowering the virus shedding titer, and controlling the release of antiviral substances. Furthermore, bifidobacteria can modulate the immune system by increasing immunoglobulins, and inducing or reducing pro- or antiinflammatory cytokines, respectively. In particular, these anti-inflammatory effects are helpful in the treatment of patients who are already suffering from infection or inflammatory diseases. This review summarizes the antimicrobial effects and mechanisms, and immunomodulatory effects of Bifidobacterium strains, suggesting the potential of bifidobacteria as an alternative or complementary treatment option.
Electrocardiographic abnormalities among late-stage non-dialysis chronic kidney disease patients

Abstract Objectives Cardiovascular disease (CVD) complication is common among chronic kidney disease (CKD) patients. Thus, knowledge about CVD and ECG abnormalities in CKD are essential due to progressive nature of the disease and increased risk of sudden cardiac death. This study aims to scrutinize the ECG abnormalities among nondialysis late-stage CKD patients. Methods A descriptive observational study was conducted at Dr. Soetomo General Hospital, Surabaya, Indonesia. Subjects were hospitalized patients with late-stage CKD between 1 January and 31 December 2019, who were consulted at the department of cardiology and vascular medicine during their initial admission at emergency room. ECG interpretation for this study was done by qualified cardiologist. Results There were 191 patients included in this study. Mean ages were 52.2 ± 11.8 years old and 51% were males. Total 143 (74.9%) patients had anemia, 111 (58.1%) had hypertension and 75 (39.3%) had type 2 diabetes mellitus. Mean serum creatinine was 10.5 ± 8.0 mg/dL. There were 176 (92.1%) patients with at least one form of ECG abnormalities. Prolonged QTc interval (36.6%), fragmented QRS complex (29.8%), poor R wave progression (24.6%), peaked T wave (22.0%) and left ventricular hypertrophy (16.7%) were the most common abnormalities. Conclusions ECG abnormalities are common among nondialysis late-stage CKD patients. Given the fact that long-term CKD influences the pathogenesis cardiovascular diseases and substantial cardiovascular mortality, there is a need to screen Indonesian CKD patients who are at risks of getting earlier complications.