Miracle-dz/UniFAR-FTUs huggingface dataset:
The complex epistemological challenge of data curation in dietary metabarcoding: Comment on “The precautionary principle and dietary DNA metabarcoding: Commonly used abundance thresholds change ecological interpretation” by Littleford‐Colquhoun et al. (2022)

In their article, Littleford‐Colquhoun et al. (2022) advise against using arbitrary relative read abundance (RRA) thresholds (i.e., minimum sequence copy thresholds) for removing low‐abundance sequences since they can increase false negative rates in dietary DNA metabarcoding data sets. The main criticisms presented against these widespread methods are that they (i) are arbitrary, often existing as standard values or defined based on researcher‐selected delineations, (ii) are subjective, varying between studies and contexts, and, most problematically, (iii) result in the exclusion of true positives, particularly rarely consumed taxa, to the detriment of ecological insight. We commend the authors for presenting a refreshing and timely perspective on this often neglected topic, which is certainly in need of greater discussion following over a decade of significant advances in dietary metabarcoding. In this complex epistemological problem of false positives versus false negatives, we feel that several of the points raised deserve additional discussion. We address these aspects below, including measured approaches to data filtration and consistent representation of RRAs, and we welcome any further discourse to solidify or refute the concepts therein.
DeepEZ: A Graph Convolutional Network for Automated Epileptogenic Zone Localization From Resting-State fMRI Connectivity

<italic>Objective:</italic> Epileptogenic zone (EZ) localization is a crucial step during diagnostic work up and therapeutic planning in medication refractory epilepsy. In this paper, we present the first deep learning approach to localize the EZ based on resting-state fMRI (rs-fMRI) data. <italic>Methods:</italic> Our network, called DeepEZ, uses a cascade of graph convolutions that emphasize signal propagation along expected anatomical pathways. We also integrate domain-specific information, such as an asymmetry term on the predicted EZ and a learned subject-specific bias to mitigate environmental confounds. <italic>Results:</italic> We validate DeepEZ on rs-fMRI collected from 14 patients with focal epilepsy at the University of Wisconsin Madison. Using cross validation, we demonstrate that DeepEZ achieves consistently high EZ localization performance (Accuracy: 0.88 <inline-formula><tex-math notation="LaTeX">$\pm$</tex-math></inline-formula> 0.03; AUC: 0.73 <inline-formula><tex-math notation="LaTeX">$\pm$</tex-math></inline-formula> 0.03) that far outstripped any of the baseline methods. This performance is notable given the variability in EZ locations and scanner type across the cohort. <italic>Conclusion:</italic> Our results highlight the promise of using DeepEZ as an accurate and noninvasive therapeutic planning tool for medication refractory epilepsy. <italic>Significance:</italic> While prior work in EZ localization focused on identifying localized aberrant signatures, there is growing evidence that epileptic seizures affect inter-regional connectivity in the brain. DeepEZ allows clinicians to harness this information from noninvasive imaging that can easily be integrated into the existing clinical workflow.
Ambient formaldehyde and mortality: A time series analysis in China

The potential health impact of low-level ambient formaldehyde has been historically overlooked. We conducted a two-stage time series analysis to investigate associations between ambient formaldehyde and daily nonaccidental, circulatory, and respiratory mortality and six subtypes based on 5,325,585 deaths in 275 Chinese counties between 2013 and 2018 and estimated a concentration-response curve to identify overall associations. After controlling for confounders from meteorological factors, air pollutants, time trend, and day of the week effect, with a 1–part per billion (ppb) increase in the daily concentration of formaldehyde on lag0 day, we found that mortality risks in nonaccidental, circulatory, and respiratory diseases increased by 0.36%, 0.36% and 0.41%, respectively. The curve indicated a possible threshold concentration at approximately 5 ppb for significant impact on nonaccidental and circulatory diseases. We suggest that ambient formaldehyde may represent a potential threat to public health and needs further investigation to support timely pollution regulation and health protection.
Defining the Selectivity of Chemical Inhibitors Used for Cytochrome P450 Reaction Phenotyping: Overcoming Selectivity Limitations with a Six-Parameter Inhibition Curve-Fitting Approach

The utility of chemical inhibitors in cytochrome P450 (CYP) reaction phenotyping is highly dependent on their selectivity and potency for their target CYP isoforms. In the present study, 17 inhibitors of CYP1A2, 2B6, 2C8, 2C9, 2C19, 2D6, and 3A4/5 commonly used in reaction phenotyping were evaluated for their cross-enzyme selectivity in pooled human liver microsomes. The data were evaluated using a statistical desirability analysis to identify (1) inhibitors of superior selectivity for reaction phenotyping and (2) optimal concentrations for each. Among the inhibitors evaluated, α-naphthoflavone, furafylline, sulfaphenazole, tienilic acid, N-benzylnirvanol, and quinidine were most selective, such that their respective target enzymes were inhibited by ∼95% without inhibiting any other CYP enzyme by more than 10%. Other commonly employed inhibitors, such as ketoconazole and montelukast, among others, were of insufficient selectivity to yield a concentration that could adequately inhibit their target enzymes without affecting other CYP enzymes. To overcome these shortcomings, an experimental design was developed wherein dose response data from a densely sampled multi-concentration inhibition curve are analyzed by a six-parameter inhibition curve function, allowing accounting of the inhibition of off-target CYP isoforms inhibition and more reliable determination of maximum targeted enzyme inhibition. The approach was exemplified using rosiglitazone N-demethylation, catalyzed by both CYP2C8 and 3A4, and was able to discern the off-target inhibition by ketoconazole and montelukast from the inhibition of the targeted enzyme. This methodology yields more accurate estimates of CYP contributions in reaction phenotyping. SIGNIFICANCE STATEMENT Isoform-selective chemical inhibitors are important tools for identifying and quantifying enzyme contributions as part of a cytochrome P450 (CYP) reaction phenotyping assessment for projecting drug-drug interactions. However, currently employed practices fail to adequately compensate for shortcomings in inhibitor selectivity and the resulting confounding impact on estimates of the CYP enzyme contribution to drug clearance. In this report, we describe a detailed half maximal inhibitory concentration (IC50) study design with 6-parameter modeling approach that yields more accurate estimates of enzyme contribution.
Molecular mechanism of S-adenosylmethionine sensing by SAMTOR in mTORC1 signaling

The mechanistic target of rapamycin–mLST8-raptor complex (mTORC1) functions as a central regulator of cell growth and metabolism in response to changes in nutrient signals such as amino acids. SAMTOR is an S-adenosylmethionine (SAM) sensor, which regulates the mTORC1 activity through its interaction with the GTPase-activating protein activity toward Rags-1 (GATOR1)-KPTN, ITFG2, C12orf66 and SZT2-containing regulator (KICSTOR) complex. In this work, we report the crystal structures of Drosophila melanogaster SAMTOR in apo form and in complex with SAM. SAMTOR comprises an N-terminal helical domain and a C-terminal SAM-dependent methyltransferase (MTase) domain. The MTase domain contains the SAM-binding site and the potential GATOR1-KICSTOR–binding site. The helical domain functions as a molecular switch, which undergoes conformational change upon SAM binding and thereby modulates the interaction of SAMTOR with GATOR1-KICSTOR. The functional roles of the key residues and the helical domain are validated by functional assays. Our structural and functional data together reveal the molecular mechanism of the SAM sensing of SAMTOR and its functional role in mTORC1 signaling.
A Mapping Review of Real-Time Movement Sonification Systems for Movement Rehabilitation

Movement sonification is emerging as a useful tool for rehabilitation, with increasing evidence in support of its use. To create such a system requires component considerations outside of typical sonification design choices, such as the dimension of movement to sonify, section of anatomy to track, and methodology of motion capture. This review takes this emerging and highly diverse area of literature and keyword-code existing real-time movement sonification systems, to analyze and highlight current trends in these design choices, as such providing an overview of existing systems. A combination of snowballing through relevant existing reviews and a systematic search of multiple databases were utilized to obtain a list of projects for data extraction. The review categorizes systems into three sections: identifying the link between physical dimension to auditory dimension used in sonification, identifying the target anatomy tracked, identifying the movement tracking system used to monitor the target anatomy. The review proceeds to analyze the systematic mapping of the literature and provide results of the data analysis highlighting common and innovative design choices used, irrespective of application, before discussing the findings in the context of movement rehabilitation. A database containing the mapped keywords assigned to each project are submitted with this review.
Mathematics in context

An important part of the role of a mathematics teacher is to present mathematics in a situated way, allowing pupils to 'work on open and closed tasks in a variety of real and abstract contexts that allow them to select the mathematics to use' (QCA, 2007a: 147). Whether you use a context-based question from a textbook, engage in an investigation that lasts for a whole lesson or are asked to deliver a set of 'functional' or 'cross-curricular' lessons, you will frequently find yourself linking concepts and methods from the mathematics curriculum to the 'real world'. Taking this approach to teaching mathematics yields a number of benefits for both the teacher and the learner: it can help pupils to construct their own understanding, promote memory, increase motivation and give a partial answer to the ever-present question of 'Why do we have to do this? i? ½ 'The reason for pupils' difficulty is explained not in terms of the conceptual complexity of the subject matter, but in terms of its apparent irrelevance and/or the teacher's inability to present it in a coherent, meaningful way. ' (Quilter and Harper, 1988: 127) However, not all contexts are equally useful or even equally valid for use in the mathematics classroom. There are important philosophical and pedagogical issues that influence how you choose contexts and how pupils come to learn the mathematics embedded within them. This chapter will explore some of those issues and offer you ideas about how you might organise your teaching, so that you can present mathematics in context for the benefit of your pupils.
Automation of AMOEBA polarizable force field for small molecules: Poltype 2

A next‐generation protocol (Poltype 2) has been developed which automatically generates AMOEBA polarizable force field parameters for small molecules. Both features and computational efficiency have been drastically improved. Notable advances include improved database transferability using SMILES, robust torsion fitting, non‐aromatic ring torsion parameterization, coupled torsion‐torsion parameterization, Van der Waals parameter refinement using ab initio dimer data and an intelligent fragmentation scheme that produces parameters with dramatically reduced ab initio computational cost. Additional improvements include better local frame assignment for atomic multipoles, automated formal charge assignment, Zwitterion detection, smart memory resource defaults, parallelized fragment job submission, incorporation of Psi4 quantum package, ab initio error handling, ionization state enumeration, hydration free energy prediction and binding free energy prediction. For validation, we have applied Poltype 2 to ~1000 FDA approved drug molecules from DrugBank. The ab initio molecular dipole moments and electrostatic potential values were compared with Poltype 2 derived AMOEBA counterparts. Parameters were further substantiated by calculating hydration free energy (HFE) on 40 small organic molecules and were compared with experimental data, resulting in an RMSE error of 0.59 kcal/mol. The torsion database has expanded to include 3543 fragments derived from FDA approved drugs. Poltype 2 provides a convenient utility for applications including binding free energy prediction for computational drug discovery. Further improvement will focus on automated parameter refinement by experimental liquid properties, expansion of the Van der Waals parameter database and automated parametrization of modified bio‐fragments such as amino and nucleic acids.
The Natural History of Insomnia: High Sleep Reactivity Interacts with Greater Life Stress to Predict the Onset of Acute Insomnia.

STUDY OBJECTIVES Prior research suggests that some individuals have a predisposition to experience insomnia following acute stressors (i.e., sleep reactivity). The present study was a proof of concept and specifically aimed to provide additional empirical evidence that the link between stressful life events and the onset of acute insomnia is moderated by sleep reactivity. METHODS 1,225 adults with a history of good sleep (Mage = 53.2 years, 68% female, 83% white) were recruited nationwide for an online study on sleep health. Participants completed surveys to assess sleep reactivity (baseline), sleep patterns (daily sleep diary), and stressful life events (weekly survey). All daily and weekly measures were completed for a one-year period. Sleep diary data were used to identify sleep initiation/maintenance difficulties, including whether they met criteria for acute insomnia at any point during the one-year interval. RESULTS Participants with high sleep reactivity compared to low sleep reactivity were at 76% increased odds of developing acute insomnia during the one-year interval. In general, greater weekly stressful life events were associated with greater insomnia during the subsequent week. Those participants with high sleep reactivity demonstrated a stronger relationship between weekly stressful life events and insomnia, such that they reported the greatest levels of insomnia following weeks where they experienced a greater number of stressful life events. CONCLUSIONS These results further support the sleep reactivity model of insomnia, and specifically, provide evidence that sleep reactivity predicts the incidence of acute insomnia in a sample of participants with no history of insomnia.
The effect of saffron supplementation on glycemic parameters: An overview of systematic reviews

Due to the widespread use of herbal medicine and evidence pointing to the health benefits of saffron supplementation, this review was performed to evaluate the effects of saffron supplementation on glycemic parameters and lipid profiles based on previous reviews. Relevant articles were retrieved from various databases, which included PubMed, Scopus, ProQuest, Web of Science, Embase, and Cochrane until 2020, with no date restrictions. The quality of the included reviews was assessed using the Assessment of Multiple Systematic Reviews (AMSTAR) checklist. Finally, of 877 obtained articles, eight reviews meeting the inclusion criteria were included for analysis. Among the eight included reviews, seven articles were meta‐analyses. In addition, one review had an average quality while seven had a good quality. A narrative description of the included reviews was performed, while a network meta‐analysis was not conducted. A brief review of the results was reported according to the weighted mean difference and mean difference. Seven included reviews assessed the effects of saffron or crocin supplementation on glycemic parameters, and six examined these effects on lipid profile parameters. Almost half of the articles reported significant effects of these supplements on glycemic parameters and lipid profiles. Taken together, results suggest that saffron supplementation may improve glycemic and lipid profile parameters; however, further high‐quality studies are needed to confirm the clinical efficacy of saffron on glycemic parameters and lipid profiles
Association of Mitochondrial DNA Copy Number with Risk of Progression of Kidney Disease

Visual Abstract Background and objectives Mitochondrial DNA copy number is a biomarker of mitochondrial function, which has been hypothesized to contribute to pathogenesis of CKD through podocyte injury, tubular epithelial cell damage, and endothelial dysfunction. The prospective association of mitochondrial DNA copy number with CKD progression has not been previously evaluated. Design, setting, participants, & measurements Chronic Renal Insufficiency Cohort study participants had serum levels of mitochondrial DNA copy number calculated from probe intensities of mitochondrial single nucleotide polymorphisms genotyped on the Illumina HumanOmni 1-Quad Array. CKD progression was defined as kidney failure or halving of eGFR from baseline. Cox proportional hazards models were used to calculate hazard ratios for mitochondrial DNA copy number and risk of CKD progression. Results Among 2943 participants, mean age was 58 years, 45% were women, and 48% self-identified as Black. There were 1077 patients who experienced CKD progression over a median follow-up of 6.5 years. The incidence rate of CKD progression was highest for those in the lowest tertile of mitochondrial DNA copy number (tertile 1, 58.1; tertile 2, 50.8; tertile 3, 46.3 per 1000 person-years). Risk for CKD progression was higher for participants with lower levels of mitochondrial DNA copy number after adjustment for established risk factors (for tertile 1 versus 3, hazard ratio, 1.28 [95% confidence interval, 1.10 to 1.50]; for tertile 2 versus 3, hazard ratio, 0.99 [95% confidence interval, 0.85 to 1.16]; trend P=0.002). Similar results were seen among those with albuminuria (for tertile 1 versus 3, hazard ratio, 1.24; 95% confidence interval, 1.05 to 1.47), but there were no statistically significant associations among individuals without albuminuria (for tertile 1 versus 3, hazard ratio, 1.04; 95% confidence interval, 0.70 to 1.53; interaction P<0.001). Conclusions These findings suggest lower mitochondrial DNA copy number is associated with higher risk of CKD progression, independent of established risk factors among patients with CKD.
Some complexities in interpreting apparent effects of hitchhiking: A commentary on Gompert et al. (2022)

We write to address recent claims by regarding the potentially important and underappreciated phenomena of “indirect selection,” the observation that neutral regions may be affected by natural selection. We argue both that this phenomenon—generally known as genetic hitchhiking—is neither new nor poorly studied, and that the patterns described by the authors have multiple alternative explanations.
The impact of postexercise blood flow restriction on local muscle endurance of a remote limb

Studies have examined the influence of postexercise blood flow restriction as a mechanism to activate muscle afferents and assess nonlocal muscle fatigue. Although these studies have assessed fatigue during maximal contractions, less is known about how these afferents may impact submaximal local muscle endurance, which was the purpose of the present study.
Polyzoa is back: The effect of complete gene sets on the placement of Ectoprocta and Entoprocta

The phylogenomic approach has largely resolved metazoan phylogeny and improved our knowledge of animal evolution based on morphology, paleontology, and embryology. Nevertheless, the placement of two major lophotrochozoan phyla, Entoprocta (Kamptozoa) and Ectoprocta (Bryozoa), remains highly controversial: Originally considered as a single group named Polyzoa (Bryozoa), they were separated on the basis of morphology. So far, each new study of lophotrochozoan evolution has still consistently proposed different phylogenetic positions for these groups. Here, we reinvestigated the placement of Entoprocta and Ectoprocta using highly complete datasets with rigorous contamination removal. Our results from maximum likelihood, Bayesian, and coalescent analyses strongly support the topology in which Entoprocta and Bryozoa form a distinct clade, placed as a sister group to all other lophotrochozoan clades: Annelida, Mollusca, Brachiopoda, Phoronida, and Nemertea. Our study favors the evolutionary scenario where Entoprocta, Cycliophora, and Bryozoa constitute one of the earliest branches among Lophotrochozoa and thus supports the Polyzoa hypothesis.
MOCSA: multiobjective optimization by conformational space annealing

We introduce a novel multiobjective optimization algorithm based on the conformational space annealing (CSA) algorithm, MOCSA. It has three characteristic features: (a) Dominance relationship and distance between solutions in the objective space are used as the fitness measure, (b) update rules are based on the fitness as well as the distance between solutions in the decision space and (c) it uses a constrained local minimizer. We have tested MOCSA on 12 test problems, consisting of ZDT and DTLZ test suites. Benchmark results show that solutions obtained by MOCSA are closer to the Pareto front and covers a wider range of the objective space than those by the elitist non-dominated sorting genetic system (NSGA2).
Online MTPA Control of IPMSM Based on Robust Numerical Optimization Technique

This paper presents an online maximum torque per ampere (MTPA) control that considers both magnetic saturation and cross-magnetization effects of interior permanent-magnet synchronous machines (IPMSMs). For IPMSM drives, especially in torque-controlled applications, torque accuracy and high-efficiency operations are important issues. They can be dealt as a constrained optimization problem to satisfy both torque reference tracking and loss-minimizing operation. In this paper, nonlinear simultaneous equations are derived from Lagrange multiplier method, which could be solved by numerical algorithms. Among them, Levenberg–Marquardt algorithm (LMA) is employed to guarantee a robust calculation of optimal current references. It is optimized to alleviate calculation burden while maintaining the stability of the proposed algorithm. In addition, a torque reference limiter is implemented to satisfy a current limit in real time. The feasibility of the proposed method is verified under various operating conditions by simulation and experimental results. Through the proposed algorithms, accurate MTPA control is achieved under not only unsaturated but also highly saturated operating conditions.