Miracle-dz/UniFAR-FTUs huggingface dataset:
Prediction of Acquired Antimicrobial Resistance for Multiple Bacterial Species Using Neural Networks

Machine learning is a proven method to predict AMR; however, the performance of any machine learning model depends on the quality of the input data. Therefore, we evaluated different methods of representing information about mutations as well as mobilizable genes, so that the information can serve as input for a robust model. We combined data from multiple bacterial species in order to develop species-independent machine learning models that can predict resistance profiles for multiple antimicrobials and species with high performance. ABSTRACT Machine learning has proven to be a powerful method to predict antimicrobial resistance (AMR) without using prior knowledge for selected bacterial species-antimicrobial combinations. To date, only species-specific machine learning models have been developed, and to the best of our knowledge, the inclusion of information from multiple species has not been attempted. The aim of this study was to determine the feasibility of including information from multiple bacterial species to predict AMR for an individual species, since this may make it easier to train and update resistance predictions for multiple species and may lead to improved predictions. Whole-genome sequence data and susceptibility profiles from 3,528 Mycobacterium tuberculosis, 1,694 Escherichia coli, 658 Salmonella enterica, and 1,236 Staphylococcus aureus isolates were included. We developed machine learning models trained by the features of the PointFinder and ResFinder programs detected to predict binary (susceptible/resistant) AMR profiles. We tested four feature representation methods to determine the most efficient way for introducing features into the models. When training the model only on the Mycobacterium tuberculosis isolates, high prediction performances were obtained for the six AMR profiles included. By adding information on ciprofloxacin from the additional 3,588 isolates, there was no reduction in performance for the other antimicrobials but an increased performance for ciprofloxacin AMR profile prediction for Mycobacterium tuberculosis and Escherichia coli. In conclusion, the species-independent models can predict multi-AMR profiles for multiple species without losing any robustness. IMPORTANCE Machine learning is a proven method to predict AMR; however, the performance of any machine learning model depends on the quality of the input data. Therefore, we evaluated different methods of representing information about mutations as well as mobilizable genes, so that the information can serve as input for a robust model. We combined data from multiple bacterial species in order to develop species-independent machine learning models that can predict resistance profiles for multiple antimicrobials and species with high performance.
The CYCLIN-DEPENDENT KINASE Module of the Mediator Complex Promotes Flowering and Reproductive Development in Pea1[OPEN]

Characterization of two loci influencing flowering initiation and reproductive development, LATE3 and LATE4, reveals an important role for the deeply conserved Mediator complex. Control of flowering time has been a major focus of comparative genetic analyses in plant development. This study reports on a forward genetic approach to define previously uncharacterized components of flowering control pathways in the long-day legume, pea (Pisum sativum). We isolated two complementation groups of late-flowering mutants in pea that define two uncharacterized loci, LATE BLOOMER3 (LATE3) and LATE4, and describe their diverse effects on vegetative and reproductive development. A map-based comparative approach was employed to identify the underlying genes for both loci, revealing that that LATE3 and LATE4 are orthologs of CYCLIN DEPENDENT KINASE8 (CDK8) and CYCLIN C1 (CYCC1), components of the CDK8 kinase module of the Mediator complex, which is a deeply conserved regulator of transcription in eukaryotes. We confirm the genetic and physical interaction of LATE3 and LATE4 and show that they contribute to the transcriptional regulation of key flowering genes, including the induction of the florigen gene FTa1 and repression of the floral repressor LF. Our results establish the conserved importance of the CDK8 module in plants and provide evidence for the function of CYCLIN C1 orthologs in the promotion of flowering and the maintenance of normal reproductive development.
The impact of chemoinformatics on drug discovery in the pharmaceutical industry

ABSTRACT Introduction: Even though there have been substantial advances in our understanding of biological systems, research in drug discovery is only just now beginning to utilize this type of information. The single-target paradigm, which exemplifies the reductionist approach, remains a mainstay of drug research today. A deeper view of the complexity involved in drug discovery is necessary to advance on this field. Areas covered: This perspective provides a summary of research areas where cheminformatics has played a key role in drug discovery, including of the available resources as well as a personal perspective of the challenges still faced in the field. Expert opinion: Although great strides have been made in the handling and analysis of biological and pharmacological data, more must be done to link the data to biological pathways. This is crucial if one is to understand how drugs modify disease phenotypes, although this will involve a shift from the single drug/single target paradigm that remains a mainstay of drug research. Moreover, such a shift would require an increased awareness of the role of physiology in the mechanism of drug action, which will require the introduction of new mathematical, computer, and biological methods for chemoinformaticians to be trained in.
Cross-Linked Cyclodextrins Bimetallic Nanocatalysts: Applications in Microwave-Assisted Reductive Aminations

The optimization of sustainable protocols for reductive amination has been a lingering challenge in green synthesis. In this context, a comparative study of different metal-loaded cross-linked cyclodextrins (CDs) were examined for the microwave (MW)-assisted reductive amination of aldehydes and ketones using either H2 or formic acid as a hydrogen source. The Pd/Cu heterogeneous nanocatalyst based on Pd (II) and Cu (I) salts embedded in a β-CD network was the most efficient in terms of yield and selectivity attained. In addition, the polymeric cross-linking avoided metal leaching, thus enhancing the process sustainability; good yields were realized using benzylamine under H2. These interesting findings were then applied to the MW-assisted one-pot synthesis of secondary amines via a tandem reductive amination of benzaldehyde with nitroaromatics under H2 pressure. The formation of a CuxPdy alloy under reaction conditions was discerned, and a synergic effect due to the cooperation between Cu and Pd has been hypothesized. During the reaction, the system worked as a bifunctional nanocatalyst wherein the Pd sites facilitate the reduction of nitro compounds, while the Cu species promote the subsequent imine hydrogenation affording structurally diverse secondary amines with high yields.
Assessment of Tumor Mutational Burden in Pediatric Tumors by Real-Life Whole-Exome Sequencing and In Silico Simulation of Targeted Gene Panels: How the Choice of Method Could Affect the Clinical Decision?

Background: Tumor mutational burden (TMB) is an emerging genomic biomarker in cancer that has been associated with improved response to immune checkpoint inhibitors (ICIs) in adult cancers. It was described that variability in TMB assessment is introduced by different laboratory techniques and various settings of bioinformatic pipelines. In pediatric oncology, no study has been published describing this variability so far. Methods: In our study, we performed whole exome sequencing (WES, both germline and somatic) and calculated TMB in 106 patients with high-risk/recurrent pediatric solid tumors of 28 distinct cancer types. Subsequently, we used WES data for TMB calculation using an in silico approach simulating two The Food and Drug Administration (FDA)-approved/authorized comprehensive genomic panels for cancer. Results: We describe a strong correlation between WES-based and panel-based TMBs; however, we show that this high correlation is significantly affected by inclusion of only a few hypermutated cases. In the series of nine cases, we determined TMB in two sequentially collected tumor tissue specimens and observed an increase in TMB along with tumor progression. Furthermore, we evaluated the extent to which potential ICI indication could be affected by variability in techniques and bioinformatic pipelines used for TMB assessment. We confirmed that this technological variability could significantly affect ICI indication in pediatric cancer patients; however, this significance decreases with the increasing cut-off values. Conclusions: For the first time in pediatric oncology, we assessed the reliability of TMB estimation across multiple pediatric cancer types using real-life WES and in silico analysis of two major targeted gene panels and confirmed a significant technological variability to be introduced by different laboratory techniques and various settings of bioinformatic pipelines.
Development of topological insulator and topological crystalline insulator nanostructures

Topological insulators (TIs), a class of quantum materials with time reversal symmetry protected gapless Dirac-surface states, have attracted intensive research interests due to their exotic electronic properties. Topological crystalline insulators (TCIs), whose gapless surface states are protected by the crystal symmetry, have recently been proposed and experimentally verified as a new class of TIs. With high surface-to-volume ratio, nanoscale TI and TCI materials such as nanowires and nanoribbons can have significantly enhanced contribution from surface states in carrier transport and are thus ideally suited for the fundamental studies of topologically protected surface state transport and nanodevice fabrication. This article will review the synthesis and transport device measurements of TIs and TCIs nanostructures.
Influence of Vegetarian Dietary Intervention on Urinary Paraben Concentrations: A Pilot Study with ‘Temple Stay’ Participants

Personal care products and cosmetics have been identified as major sources of paraben exposure among humans. However, the contribution of dietary factors has not been well understood. We recruited temple stay participants (n = 25) who followed a strict Buddhist vegetarian diet during a five-day period, and assessed the influence of this lifestyle change, employing their urine samples collected before and after the temple stay. Before the temple stay, methylparaben (MeP) was detected at the highest levels, followed by ethylparaben (EtP), propylparaben (PrP), butylparaben (BuP), and benzophenones (BPs) in the urine samples. Following the temple stay, the urinary EtP concentrations remarkably increased from 14.0 to 105 μg/L, and were around two orders of magnitude higher than those reported from other countries. Dietary factors associated with the temple diet may partly explain the increase, because EtP is allowed in Korea for seasoning and condiments, which are frequently added in vegetarian diets. Following the temple stay, however, MeP, PrP, and BPs did not show significant decreasing trends. In contrast, BuP levels decreased significantly, especially in male urine samples, that is, from 3.60 to 1.03 μ/L, suggesting a reduced use of certain personal care products during the temple stay. Our observations outline the potential importance of dietary factors on EtP exposure, and might help explain its high exposure levels among Korean population.
An evolutionary switch from sibling rivalry to sibling cooperation, caused by a sustained loss of parental care

Significance The evolution of sibling rivalry is a classic problem in behavioral ecology. Our approach of observing the experimental evolution of sibling interactions in real time reveals three key insights. First, when parents provide parental care, siblings evolve to compete. Parental care compensates for the costs of sibling rivalry. Second, when parents do not supply care, siblings evolve to cooperate. Sibling cooperation compensates for the loss of parental care. Third, rapid evolutionary switching between sibling rivalry and sibling cooperation is possible because siblings induce greater levels of rivalry (or cooperation) in each other. This generates positive evolutionary feedback, rapidly locking larvae into evolving greater levels of competition (or cooperation) in the presence (or absence) of parental care. Sibling rivalry is commonplace within animal families, yet offspring can also work together to promote each other’s fitness. Here we show that the extent of parental care can determine whether siblings evolve to compete or to cooperate. Our experiments focus on the burying beetle Nicrophorus vespilloides, which naturally provides variable levels of care to its larvae. We evolved replicate populations of burying beetles under two different regimes of parental care: Some populations were allowed to supply posthatching care to their young (Full Care), while others were not (No Care). After 22 generations of experimental evolution, we found that No Care larvae had evolved to be more cooperative, whereas Full Care larvae were more competitive. Greater levels of cooperation among larvae compensated for the fitness costs caused by parental absence, whereas parental care fully compensated for the fitness costs of sibling rivalry. We dissected the evolutionary mechanisms underlying these responses by measuring indirect genetic effects (IGEs) that occur when different sibling social environments induce the expression of more cooperative (or more competitive) behavior in focal larvae. We found that indirect genetic effects create a tipping point in the evolution of larval social behavior. Once the majority of offspring in a brood start to express cooperative (or competitive) behavior, they induce greater levels of cooperation (or competition) in their siblings. The resulting positive feedback loops rapidly lock larvae into evolving greater levels of cooperation in the absence of parental care and greater levels of rivalry when parents provide care.
Equilibrium States and Their Stability in the Head-Direction Ring Network

Head-direction cells have been found in several areas in the mammalian brains. The firing rate of an ideal head-direction cell reaches its peak value only when the animal's head points in a specific direction, and this preferred direction stays the same regardless of spatial location. In this paper we combine mathematical analytical techniques and numerical simulations to fully analyze the equilibrium states of a generic ring attractor network, which is a widely used modeling framework for the head-direction system. Under specific conditions, all solutions of the ring network are bounded, and there exists a Lyapunov function that guarantees the stability of the network for any given inputs, which may come from multiple sources in the biological system, including self-motion information for inertially based updating and landmark information for calibration. We focus on the first few terms of the Fourier series of the ring network to explicitly solve for all possible equilibrium states, followed by a stability analysis based on small perturbations. In particular, these equilibrium states include the standard single-peaked activity pattern as well as double-peaked activity pattern, whose existence is unknown but has testable experimental implications. To our surprise, we have also found an asymmetric equilibrium activity profile even when the network connectivity is strictly symmetric. Finally we examine how these different equilibrium solutions depend on the network parameters and obtain the phase diagrams in the parameter space of the ring network.
Effectiveness of an Empathic Chatbot in Combating Adverse Effects of Social Exclusion on Mood

From past research it is well known that social exclusion has detrimental consequences for mental health. To deal with these adverse effects, socially excluded individuals frequently turn to other humans for emotional support. While chatbots can elicit social and emotional responses on the part of the human interlocutor, their effectiveness in the context of social exclusion has not been investigated. In the present study, we examined whether an empathic chatbot can serve as a buffer against the adverse effects of social ostracism. After experiencing exclusion on social media, participants were randomly assigned to either talk with an empathetic chatbot about it (e.g., “I’m sorry that this happened to you”) or a control condition where their responses were merely acknowledged (e.g., “Thank you for your feedback”). Replicating previous research, results revealed that experiences of social exclusion dampened the mood of participants. Interacting with an empathetic chatbot, however, appeared to have a mitigating impact. In particular, participants in the chatbot intervention condition reported higher mood than those in the control condition. Theoretical, methodological, and practical implications, as well as directions for future research are discussed.
Acute Sprint Interval Exercise Increases Both Cognitive Functions and Peripheral Neurotrophic Factors in Humans: The Possible Involvement of Lactate

There is increasing attention to sprint interval exercise (SIE) training as a time-efficient exercise regime. Recent studies, including our own (Kujach et al., 2018), have shown that acute high-intensity intermittent exercise can improve cognitive function; however, the neurobiological mechanisms underlying the effect still remain unknown. We thus examined the effects of acute SIE on cognitive function by monitoring the peripheral levels of growth and neurotrophic factors as well as blood lactate (LA) as potential mechanisms. Thirty-six young males participated in the current study and were divided into two groups: SIE (n = 20; mean age: 21.0 ± 0.9 years) and resting control (CTR) (n = 16; mean age: 21.7 ± 1.3 years). The SIE session consisted of 5 min of warm-up exercise and six sets of 30 s of all-out cycling exercise followed by 4.5 min of rest on a cycling-ergometer. Blood samples to evaluate the changes of serum concentrations of brain-derived neurotrophic factor (BDNF), insulin-like growth factor-1 (IGF-1), vascular endothelial growth factor (VEGF), and blood LA were obtained at three time points: before, immediately after, and 60 min after each session. A Stroop task (ST) and trail making test (TMT) parts A and B were used to assess cognitive functions. Acute SIE shortened response times for both the ST and TMT A and B. Meanwhile, the peripheral levels of BDNF, IGF-1, and VEGF were significantly increased after an acute bout of SIE compared to those in CTR. In response to acute SIE, blood LA levels significantly increased and correlated with increased levels of BDNF, IGF-1, and VEGF. Furthermore, cognitive function and BDNF are found to be correlated. The current results suggest that SIE could have beneficial effects on cognitive functions with increased neuroprotective factors along with peripheral LA concentration in humans.
Amphetamine Derivatives as Monoamine Oxidase Inhibitors

Amphetamine and its derivatives exhibit a wide range of pharmacological activities, including psychostimulant, hallucinogenic, entactogenic, anorectic, or antidepressant effects. The mechanisms of action underlying these effects are usually related to the ability of the different amphetamines to interact with diverse monoamine transporters or receptors. Moreover, many of these compounds are also potent and selective monoamine oxidase inhibitors. In the present work, we review how structural modifications on the aromatic ring, the amino group and/or the aliphatic side chain of the parent scaffold, modulate the enzyme inhibitory properties of hundreds of amphetamine derivatives. Furthermore, we discuss how monoamine oxidase inhibition might influence the pharmacology of these compounds.
Evidence-Based Science Communication

Effective science communication can empower research and innovation systems to address global challenges and put public interests at the heart of how knowledge is produced, shared, and applied. For science communication to play this mediating role effectively, we propose a more integrated and “evidence-based” approach. This commentary identifies key issues facing the science communication field. It suggests a series of prescriptions, inspired by the impact of “evidence-based medicine” over the past decades. In practice, evidence-based science communication should combine professional expertise and skills with the best available evidence from systematic research. Steps required to achieve this outcome include more quality assurance in science communication research, significant changes in teaching and training, and improved interfaces between science communication research and practice.
Necroptosis and Caspase-2-Mediated Apoptosis of Astrocytes and Neurons, but Not Microglia, of Rat Hippocampus and Parenchyma Caused by Angiostrongylus cantonensis Infection

Infection with the roundworm Angiostrongylus cantonensis is the main cause of eosinophilic meningitis worldwide. The underlying molecular basis of the various pathological outcomes in permissive and non-permissive hosts infected with A. cantonensis remains poorly defined. In the present study, the histology of neurological disorders in the central nervous system (CNS) of infected rats was assessed by using hematoxylin and eosin staining. Quantitative reverse transcription polymerase chain reaction (RT-qPCR), western blot and immunofluorescence (IF) were used in evolutions of the transcription and translation levels of the apoptosis-, necroptosis-, autophagy-, and pyroptosis-related genes. The distribution of apoptotic and necroptotic cells in the rat hippocampus and parenchyma was further detected using flow cytometry, and the features of the ultrastructure of the cells were examined by transmission electron microscopy (TEM). The inflammatory response upon CNS infection with A. cantonensis evolved, as characterized by the accumulation of a small number of inflammatory cells under the thickened meninges, which peaked at 21 days post-infection (dpi) and returned to normal by 35 dpi. The transcription levels and translation of caspase-2, caspase-8, RIP1 and RIP3 increased significantly at 21 and 28 dpi but decreased sharply at 35 dpi compared to those in the normal control group. However, the changes in the expression of caspase-1, caspase-3, caspase-11, Beclin-1 and LC3B were not obvious, suggesting that apoptosis and necroptosis but not autophagy or pyroptosis occurred in the brains of infected animals at 21 and 28 dpi. The results of RT-qPCR, western blot analysis, IF, flow cytometry and TEM further illustrated that necroptosis and caspase-2-mediated apoptosis occurred in astrocytes and neurons but not in microglia in the parenchyma and hippocampus of infected animals. This study provides the first evidence that neuronal and astrocytic necroptosis and caspase-2-mediated apoptosis are induced by A. cantonensis infection in the parenchymal and hippocampal regions of rats at 21 and 28 dpi but these processes are negligible at 35 dpi. These findings enhance our understanding of the pathogenesis of A. cantonensis infection and provide new insights into therapeutic approaches targeting the occurrence of cell death in astrocytes and neurons in infected patients.