Miracle-dz/UniFAR-FTUs huggingface dataset:
Pharmacotherapy of Alzheimer’s Disease: Seeking Clarity in a Time of Uncertainty

Alzheimer’s disease (AD) is recognized as a major health hazard that mostly affects people older than 60 years. AD is one of the biggest medical, economic, and social concerns to patients and their caregivers. AD was ranked as the 5th leading cause of global deaths in 2016 by the World Health Organization (WHO). Many drugs targeting the production, aggregation, and clearance of Aβ plaques failed to give any conclusive clinical outcomes. This mainly stems from the fact that AD is not a disease attributed to a single-gene mutation. Two hallmarks of AD, Aβ plaques and neurofibrillary tangles (NFTs), can simultaneously induce other AD etiologies where every pathway is a loop of consequential events. Therefore, the focus of recent AD research has shifted to exploring other etiologies, such as neuroinflammation and central hyperexcitability. Neuroinflammation results from the hyperactivation of microglia and astrocytes that release pro-inflammatory cytokines due to the neurological insults caused by Aβ plaques and NFTs, eventually leading to synaptic dysfunction and neuronal death. This review will report the failures and side effects of many anti-Aβ drugs. In addition, emerging treatments targeting neuroinflammation in AD, such as nonsteroidal anti-inflammatory drugs (NSAIDs) and receptor-interacting serine/threonine protein kinase 1 (RIPK1), that restore calcium dyshomeostasis and microglia physiological function in clearing Aβ plaques, respectively, will be deliberately discussed. Other novel pharmacotherapy strategies in treating AD, including disease-modifying agents (DMTs), repurposing of medications used to treat non-AD illnesses, and multi target-directed ligands (MTDLs) are also reviewed. These approaches open new doors to the development of AD therapy, especially combination therapy that can cater for several targets simultaneously, hence effectively slowing or stopping AD.
Analysis of COMPASS, a New Comprehensive Plasmid Database Revealed Prevalence of Multireplicon and Extensive Diversity of IncF Plasmids

Plasmids are genetic elements that enable rapid adaptation and evolution by transferring genes conferring selective advantages to their hosts. Conjugative plasmids are predominantly responsible for the global dissemination of antimicrobial resistance, representing an important threat to global health. As the number of plasmid sequences grows exponentially, it becomes critical to depict the global diversity and decipher the distribution of circulating plasmids in the bacterial community. To this end, we created COMPASS, a novel and comprehensive database compiling 12,084 complete plasmids with associated metadata from 1571 distinct species isolated worldwide over more than 100 years. The curation of the database allowed us to identify identical plasmids across different bacteria revealing mainly intraspecies dissemination and rare cases of horizontal transmission. We outlined and analyzed all relevant features, plasmid properties, host range and characterized their replication and mobilization systems. After an exhaustive comparison of PlasmidFinder and MOB-typer, the MOB-typer-based analysis revealed that the current knowledge embedded in the current typing schemes fails to classify all the plasmid sequences collected in COMPASS. We were able to categorize 6828 and 5229 plasmids by replicon and MOB typing, respectively, mostly associated with Proteobacteria and Firmicutes. We then searched for the presence of multiple core genes involved in replication and propagation. Our results showed that 2403 plasmids carried multiple replicons that were distributed in 206 bacterial species. The co-integration of replicon types from different incompatibility (Inc) groups is an adaptive mechanism, which plays an important role in plasmid survival and dissemination by extending their host range. Our results highlight the crucial role of IncF alleles (present in 56% of all multireplicons) and revealed that IncH, IncR, and IncU replicons were also frequently carried in multireplicons. Here, we provided a comprehensive picture of the different IncF subtypes by identifying 20 different profiles in 849 IncF multireplicons, which were mostly associated with Enterobacteriaceae. These results could provide the basis for a novel IncF plasmid nomenclature based on different allelic profiles.
The Ventrolateral Periaqueductal Gray Contributes to Depressive-Like Behaviors in Recovery of Inflammatory Bowel Disease Rat Model

Background Patients with inflammatory bowel disease (IBD) experience depression, even in the remission phase of IBD symptoms. Although mapping depression-associated brain regions through the gut-brain axis can contribute to understanding the process, the mechanisms remain unclear. Our previous results support the idea that glutamatergic transmission in the ventrolateral periaqueductal gray (vlPAG) mediates stress-induced depression-like behaviors. Thus, we hypothesize that the vlPAG plays a role in regulating depression during remission of IBD. Methods We used dextran sulfate sodium (DSS)-induced visceral pain model to evoke depression-like behaviors, assessed by tail suspension test (TST) and sucrose preference test (SPT), and electrophysiological recordings from vlPAG. Results Symptoms of animals modeling IBD were relieved by replacing DSS solution with normal drinking water, but their depression-like behaviors sustained. Moreover, the impairment of glutamatergic neurotransmission in vlPAG was sustained as well. Pharmacologically, microinfusion of the glutamate receptor 1 (GluR1) antagonist NASPM into vlPAG mimicked the depression-like behaviors. Furthermore, intra-vlPAG application of AMPA and AMPA receptor-mediated antidepressant (2R,6R)-hydroxynorketamine [(2R,6R)-HNK] reversed the DSS-induced depression-like behaviors in the remission phase of visceral abnormalities. Conclusion Our results suggest that vlPAG glutamatergic transmission mediates depression-like behaviors during remission of DSS-induced visceral pain, suggesting that vlPAG mapping to the gut-brain axis contributes to depression during remission of IBD.
Xeno-miRNA in Maternal-Infant Immune Crosstalk: An Aid to Disease Alleviation

Human milk is a complex liquid that contains multifaceted compounds which provide nutrition to infants and helps to develop their immune system. The presence of secretory immunoglobulins (IgA), leucocytes, lysozyme, lactoferrin, etc., in breast milk and their role in imparting passive immunity to infants as well as modulating development of an infant's immune system is well-established. Breast milk miRNAs (microRNAs) have been found to be differentially expressed in diverse tissues and biological processes during various molecular functions. Lactation is reported to assist mothers and their offspring to adapt to an ever-changing food supply. It has been observed that certain subtypes of miRNAs exist that are codified by non-human genomes but are still present in circulation. They have been termed as xeno-miRNA (XenomiRs). XenomiRs in humans have been found from various exogenous sources. Route of entry in human systems have been mainly dietary. The possibility of miRNAs taken up into mammalian circulation through diet, and thereby effecting gene expression, is a distinct possibility. This mechanism suggests an interesting possibility that dietary foods may modulate the immune strength of infants via highly specific post-transcriptional regulatory information present in mother's milk. This serves as a major breakthrough in understanding the fundamentals of nutrition and cross-organism communication. In this review, we elaborate and understand the complex crosstalk of XenomiRs present in mother's milk and their plausible role in modulating the infant immune system against infectious and inflammatory diseases.
Assessing the Identity of Commercial Herbs From a Cambodian Market Using DNA Barcoding

In Cambodia, medicinal plants are often used to treat various illnesses. However, the identities of many medicinal plants remain unknown. In this study, we collected 50 types of traditional Cambodian medicinal plants that could not be identified by their appearance from a domestic market. We utilized the DNA barcoding technique, combined with the literature survey, to trace their identities. In the end, 33 species were identified at the species level and 7 species were identified at the genus level. The ethnopharmacological information of 33 medicinal plants was documented. The DNA barcoding technique is useful in the identification of medicinal plants with no previous information.
Relationship Between Electrical Instability and Pumping Performance During Ventricular Tachyarrhythmia: Computational Study

There are representative electrical parameters for understanding the mechanism of reentrant waves in studies on tachyarrhythmia, namely the action potential duration (APD), dominant frequency, phase singularity, and filament. However, there are no studies that have directly identified the correlation between these electrophysiological parameters and cardiac contractility. Therefore, we have identified individual and integrative correlations between these electrical phenomena and contractility during tachyarrhythmia by deriving regression equations and also investigated the electrophysiological parameters affecting cardiac contractility during tachyarrhythmia. We simulated ventricular tachyarrhythmia with 48 types of electrical patterns by applying four reentry generation methods and changing the electrical conductivity of the potassium channel, which has the greatest effect on ventricular tissue. The mechanical responses reflecting electrical complexity were obtained through deterministic simulations of excitation–contraction coupling. We used the stroke volume and amplitude of myocardial tension (ampTens) as the variables representing contractility. We derived stochastic models through single- and multivariable regression analyses to identify the electrical parameters affecting contractility during tachyarrhythmia. In single-variable regression analysis, the APD, dominant frequency, and filament, excluding phase singularity, have statistically significant correlations with the stroke volume and ampTens. Among them, the APD has the maximum influence on these two mechanical parameters (standard beta coefficient: 0.859 for stroke volume, 0.930 for ampTens). The stochastic model using all four electrical parameters fails to accurately predict contractility owing to the multicollinearity between the APD and dominant frequency. We have rederived the multi-variable stochastic model using three electrical parameters without the APD. The filament has the greatest effect on the stroke volume stochastically (standard beta coefficient: 0.853 and 0.752). The dominant frequency has the greatest effect on ampTens statistically (standard beta coefficient: −0.813). We conclude that among the electrical parameters, the APD has the highest individual influence on mechanical contraction, and the filament has the highest integrative influence in both statistical terms.
Bottom-Up Construction of Complex Biomolecular Systems With Cell-Free Synthetic Biology

Cell-free systems offer a promising approach to engineer biology since their open nature allows for well-controlled and characterized reaction conditions. In this review, we discuss the history and recent developments in engineering recombinant and crude extract systems, as well as breakthroughs in enabling technologies, that have facilitated increased throughput, compartmentalization, and spatial control of cell-free protein synthesis reactions. Combined with a deeper understanding of the cell-free systems themselves, these advances improve our ability to address a range of scientific questions. By mastering control of the cell-free platform, we will be in a position to construct increasingly complex biomolecular systems, and approach natural biological complexity in a bottom-up manner.
Distribution Patterns of DNA N6-Methyladenosine Modification in Non-coding RNA Genes

N6-methyladenosine (6mA) DNA modification played an important role in epigenetic regulation of gene expression. And the aberrational expression of non-coding genes, as important regular elements of gene expression, was related to many diseases. However, the distribution and potential functions of 6mA modification in non-coding RNA (ncRNA) genes are still unknown. In this study, we analyzed the 6mA distribution of ncRNA genes and compared them with protein-coding genes in four species (Arabidopsis thaliana, Caenorhabditis elegans, Drosophila melanogaster, and Homo sapiens) using single-molecule real-time (SMRT) sequencing data. The results indicated that the consensus motifs of short nucleotides at 6mA location were highly conserved in four species, and the non-coding gene was less likely to be methylated compared with protein-coding gene. Especially, the 6mA-methylated lncRNA genes were expressed significant lower than these genes without methylation in A. thaliana (p = 3.295e-4), D. melanogaster (p = 3.439e-11), and H. sapiens (p = 9.087e-3) all four species. The detection and distribution profiling of 6mA modification in ncRNA regions from four species reveal that 6mA modifications may have effects on their expression level.
The Role of B7 Family Molecules in Maternal–Fetal Immunity

Pregnancy is a complex but well-arranged process, and a healthy fetus requires immune privilege and surveillance in the presence of paternally derived antigens. Maternal and fetal cells interact at the maternal–fetal interface. The upregulation and downregulation of maternal immunity executed by the leukocyte population predominantly depend on the activity of decidual natural killer cells and trophoblasts and are further modulated by a series of duplex signals. The B7 family, which consists of B7-1, B7-2, B7-H1, B7-DC, B7-H2, B7-H3, B7-H4, B7-H5, BTNL2, B7-H6, and B7-H7, is one of the most characterized and widely distributed signaling molecule superfamilies and conducts both stimulatory and inhibitory signals through separate interactions. In particular, the roles of B7-1, B7-2, B7-H1, and their corresponding receptors in the progression of normal pregnancy and some pregnancy complications have been extensively studied. Together with the TCR–MHC complex, B7 and its receptors play a critical role in cell proliferation and cytokine secretion. Depending on this ligand–receptor crosstalk, the balance between the tolerance and rejection of the fetus is perfectly maintained. This review aims to provide an overview of the current knowledge of the B7 family and its functions in regulating maternal–fetal immunity through individual interactions.
Psychological Treatments for People With Severe and Enduring Anorexia Nervosa: A Mini Review

This Mini-Review presents recent research into evidence for psychological treatments for people with severe and enduring anorexia nervosa (SEAN). Two psychological therapies, specialist supportive clinical management (SSCM), and cognitive behavior therapy for anorexia nervosa (CBT-AN) have limited (one randomized controlled study) evidence of efficacy. Both have had adaptations for SEAN, notably with revision of the primary treatment goal of improved quality of life and full weight recovery a secondary goal. A major issue with existing studies is poor definition of SEAN, and the large deficit in research that has used an agreed definition of SEAN. In particular, it may be problematic to extrapolate from studies of people with either severe and/or enduring but not intractable or “resistant” illness. People with longstanding AN who have not received evidence based care should be offered this with an expectation of recovery. Similarly, people with SEAN may be offered care with judicious mitigation of expectations. In the future, trials should include people with SEAN clearly defined. Trials with a subsample of participants likely to have SEAN, if identified at randomisation, are an opportunity for secondary analyses of such participants. This would widen the evidence base for psychological treatments providing hope for people with this devastating illness. Finally, there is an urgent need not only to strengthen our existing knowledge with studies of sufficient power, but also, fundamentally, to derive novel conceptualizations of what “treatment” involves.
Repeated Paced Mating Increases the Survival of New Neurons in the Accessory Olfactory Bulb

In female rats, the first sexual experience under paced mating conditions increases the number of newborn cells that migrate into the granular layer of the accessory olfactory bulb (AOB). Repeated paced mating has a potentiating effect on the number of new neurons that migrate to the AOB compared with a single session 15 days after paced mating. On the other hand, one paced mating session does no increases the survival of new cells 45 days after mating. In the present study, we evaluated if four paced mating sessions could increase the survival of new neurons in the AOB and main olfactory bulb (MOB) 45 days after females mated. Sexually naive female rats were ovariectomized, hormonally supplemented and randomly assigned to one of five groups: (1) Control, no sexual contact (C); (2) Four sessions in which females were exposed, without mating, to a sexually experience male rat (SE); (3) One session of paced mating (PM1); (4) Four sessions of paced mating (PM4); and (5) Four sessions of non-paced mating (NPM4). In the first behavioral test, females received the DNA synthesis marker 5-bromo-2′deoxyuridine and were euthanized 45 days later. Our data showed that the number of new cells that survived in the mitral cell layer of the AOB decreased when females were exposed to a sexually active male, in comparison to females that mated once pacing the sexual interaction. Repeated sexual behavior in pacing conditions did not increase the survival of new cells in other layers of the MOB and AOB. However, a significant increase in the percentage of new neurons in the granular and glomerular layers of the AOB and granular layer of the MOB was observed in females that mated in four sessions pacing the sexual interaction. In the group that paced the sexual interaction for one session, a significant increase in the percentage of neurons was observed in the glomerular layer of the AOB. Our data suggest that repeated paced mating increases the percentage of new neurons that survive in the olfactory bulb of female rats.
Evaluating the Causal Role of Gut Microbiota in Type 1 Diabetes and Its Possible Pathogenic Mechanisms

Type 1 diabetes (T1D) is a multifactorial autoimmune disease mediated by genetic, epigenetic, and environmental factors. In recent years, the emergence of high-throughput sequencing has allowed us to investigate the role of gut microbiota in the development of T1D. Significant changes in the composition of gut microbiome, also termed dysbiosis, have been found in subjects with clinical or preclinical T1D. However, whether the dysbiosis is a cause or an effect of the disease remains unclear. Currently, increasing evidence has supported a causal link between intestine microflora and T1D development. The current review will focus on recent research regarding the associations between intestine microbiome and T1D progression with an intention to evaluate the causality. We will also discuss the possible mechanisms by which imbalanced gut microbiota leads to the development of T1D.
Genetic Analysis for Cooking and Eating Quality of Super Rice and Fine Mapping of a Novel Locus qGC10 for Gel Consistency

Rice (Oryza sativa L.) is an important cereal that provides food for more than half of the world’s population. Besides grain yield, improving grain quality is also essential to rice breeders. Amylose content (AC), gelatinization temperature (GT) and gel consistency (GC) are considered to be three indicators for cooking and eating quality in rice. Using a genetic map of RILs derived from the super rice Liang-You-Pei-Jiu with high-density SNPs, we detected 3 QTLs for AC, 3 QTLs for GT, and 8 QTLs for GC on chromosomes 3, 4, 5, 6, 10, and 12. Wx locus, an important determinator for AC and GC, resided in one QTL cluster for AC and GC, qAC6 and qGC6 here. And a novel major QTL qGC10 on chromosome 10 was identified in both Lingshui and Hangzhou. With the BC4F2 population derived from a CSSL harboring the segment for qGC10 from 93-11 in PA64s background, it was fine mapped between two molecular markers within 181 kb region with 27 annotated genes. Quantitative real-time PCR results showed that eight genes were differentially expressed in endosperm of two parents. After DNA sequencing, only LOC_Os10g04900, which encodes a F-box domain containing protein, has 2 bp deletion in the exon of PA64s, resulting in a premature stop codon. Therefore, LOC_Os10g04900 is considered to be the most likely candidate gene for qGC10 associated with gel consistency. Identification of qGC10 provides a new genetic resource for improvement of rice quality.
DISGD: A Distributed Shared-nothing Matrix Factorization for Large Scale Online Recommender Systems

With the web-scale data volumes and high velocity of generation rates, it has become crucial that the training process for recommender systems be a continuous process which is performed on live data, i.e., on data streams . In practice, such systems have to address three main requirements including the ability to adapt their trained model with each incoming data element, the ability to handle concept drifts and the ability to scale with the volume of the data. In principle, matrix factorization is one of the popular approaches to train a recommender model. Stochastic Gradient Descent (SGD) has been a successful optimization approach for matrix factorization. Several approaches have been proposed that handle the first and second requirements. For the third requirement, in the realm of data streams, distributed approaches depend on a shared memory architecture. This requires obtaining locks before performing updates. In general, the success of main-stream big data processing systems is supported by their shared-nothing architecture. In this paper, we propose DISGD , a distributed shared-nothing variant of an incremental SGD. The proposal is motivated by an observation that with large volumes of data, the overwrite of updates, lock-free updates, does not affect the result with sparse user-item matrices. Compared to the baseline incremental approach, our evaluation on several datasets shows not only improvement in processing time but also improved recall by 55%.
BalanSiNG: Fast and Scalable Generation of Realistic Signed Networks

How can we e ciently generate large-scale signed networks following real-world properties? Due to its rich modeling capability of representing trust relations as positive and negative edges, signed networks have spurred much interests with various applications. Despite its importance, however, existing models for generating signed networks do not correctly re ect properties of real-world signed networks. In this paper, we propose BalanSiNG, a novel, scalable, and fully parallelizable method for generating large-scale signed networks following realistic properties. We identify a self-similar balanced structure observed from a real-world signed network, and simulate the self-similarity via Kronecker product. Then, we exploit noise and careful weighting of signs such that our resulting network obeys various properties of real-world signed networks. BalanSiNG is easily parallelizable, and we implement it using Spark. Extensive experiments show that BalanSiNG ef-ciently generates the most realistic signed networks satisfying various desired properties.