Miracle-dz/UniFAR-FTUs huggingface dataset:
Characterization of ligand-induced thermal stability of the human organic cation transporter 2 (OCT2)

Introduction: The human organic cation transporter 2 (OCT2) is involved in the transport of endogenous quaternary amines and positively charged drugs across the basolateral membrane of proximal tubular cells. In the absence of a structure, the progress in unraveling the molecular basis of OCT2 substrate specificity is hampered by the unique complexity of OCT2 binding pocket, which seemingly contains multiple allosteric binding sites for different substrates. Here, we used the thermal shift assay (TSA) to better understand the thermodynamics governing OCT2 binding to different ligands. Methods: Molecular modelling and in silico docking of different ligands revealed two distinct binding sites at OCT2 outer part of the cleft. The predicted interactions were assessed by cis-inhibition assay using [3H]1-methyl-4-phenylpyridinium ([3H]MPP+) as a model substrate, or by measuring the uptake of radiolabeled ligands in intact cells. Crude membranes from HEK293 cells harboring human OCT2 (OCT2-HEK293) were solubilized in n-Dodecyl-β-D-Maltopyranoside (DDM), incubated with the ligand, heated over a temperature gradient, and then pelleted to remove heat-induced aggregates. The OCT2 in the supernatant was detected by western blot. Results: Among the compounds tested, cis-inhibition and TSA assays showed partly overlapping results. Gentamicin and methotrexate (MTX) did not inhibit [3H]MPP+ uptake but significantly increased the thermal stabilization of OCT2. Conversely, amiloride completely inhibited [3H]MPP+ uptake but did not affect OCT2 thermal stabilization. [3H]MTX intracellular level was significantly higher in OCT2-HEK293 cells than in wild type cells. The magnitude of the thermal shift (ΔTm) did not provide information on the binding. Ligands with similar affinity showed markedly different ΔTm, indicating different enthalpic and entropic contributions for similar binding affinities. The ΔTm positively correlated with ligand molecular weight/chemical complexity, which typically has high entropic costs, suggesting that large ΔTm reflect a larger displacement of bound water molecules. Discussion: In conclusion, TSA might represent a viable approach to expand our knowledge on OCT2 binding descriptors.
Triatoma pallidipennis (Stål, 1872) (Hemiptera: Reduviidae) and its potential for infestation in Tecozautla, Hidalgo state, Mexico

ABSTRACT: Triatoma pallidipennis is an exclusive and widely distributed species in Mexico and one of the three main vectors that transmit Chagas disease in the country. The state of Hidalgo is an endemic area for Chagas disease where the presence of several species of triatomines has been reported. The objective of our work was to describe the morphology, colonization process, and reproductive behavior of T. pallidipennis in Guadalupe, Tecozautla, two years after the first collection of a specimen in this region. A total of 28 specimens was collected at both domicile and peridomicile, showing a 17.8% infection rate. The main collection site was a woodshed, and despite the collection of adults in the dwelling, we did not find eggs, exuviae, or nymphs. One female monitored from collection day until death laid 566 eggs, with a hatching rate of 95%, showing an increase of oviposition when cohabited with a male. The results showed the capacity that T. pallidipennis has to infest areas (mainly human dwellings) when it settles down, which would imply a risk for the population that lives in the locality.
Unsupervised Learning of Graph Matching With Mixture of Modes via Discrepancy Minimization

Graph matching (GM) has been a long-standing combinatorial problem due to its NP-hard nature. Recently (deep) learning-based approaches have shown their superiority over the traditional solvers while the methods are almost based on supervised learning which can be expensive or even impractical. We develop a unified unsupervised framework from matching two graphs to multiple graphs, without correspondence ground truth for training. Specifically, a Siamese-style unsupervised learning framework is devised and trained by minimizing the discrepancy of a second-order classic solver and a first-order (differentiable) Sinkhorn net as two branches for matching prediction. The two branches share the same CNN backbone for visual graph matching. Our framework further allows unsupervised learning with graphs from a mixture of modes which is ubiquitous in reality. Specifically, we develop and unify the graduated assignment (GA) strategy for matching two-graph, multi-graph, and graphs from a mixture of modes, whereby two-way constraint and clustering confidence (for mixture case) are modulated by two separate annealing parameters, respectively. Moreover, for partial and outlier matching, an adaptive reweighting technique is developed to suppress the overmatching issue. Experimental results on real-world benchmarks including natural image matching show our unsupervised method performs comparatively and even better against two-graph based supervised approaches.
Antenna-coupled microcavities for enhanced infrared photo-detection

We demonstrate mid-infrared detectors embedded into an array of double-metal nano-antennas. The antennas act as microcavities that squeeze the electric field into thin semiconductor layers, thus enhancing the detector responsivity. Furthermore, thanks to the ability of the antennas to gather photons from an area larger than the device's physical dimensions, the dark current is reduced without hindering the photo-generation rate. In these devices, the background-limited performance is improved with a consequent increase of the operating temperature. Our results illustrate how the antenna-coupled microcavity concept can be applied to enhance the performances of infrared opto-electronic devices.
Improved computation of Lagrangian tissue displacement and strain for cine DENSE MRI using a regularized spatiotemporal least squares method

Introduction In displacement encoding with stimulated echoes (DENSE), tissue displacement is encoded in the signal phase such that the phase of each pixel in space and time provides an independent measurement of absolute tissue displacement. Previously for DENSE, estimation of Lagrangian displacement used two steps: first a spatial interpolation and, second, least squares fitting through time to a Fourier or polynomial model. However, there is no strong rationale for such a through-time model, Methods To compute the Lagrangian displacement field from DENSE phase data, a minimization problem is introduced to enforce fidelity with the acquired Eulerian displacement data while simultaneously providing model-independent regularization in space and time, enforcing only spatiotemporal smoothness. A regularized spatiotemporal least squares (RSTLS) method is used to solve the minimization problem, and RSTLS was tested using two-dimensional DENSE data from 71 healthy volunteers. Results The mean absolute percent error (MAPE) between the Lagrangian displacements and the corresponding Eulerian displacements was significantly lower for the RSTLS method vs. the two-step method for both x- and y-directions (0.73±0.59 vs 0.83 ±0.1, p < 0.05) and (0.75±0.66 vs 0.82 ±0.1, p < 0.05), respectively. Also, peak early diastolic strain rate (PEDSR) was higher (1.81±0.58 (s-1) vs. 1.56±0. 63 (s-1), p<0.05) and the strain rate during diastasis was lower (0.14±0.18 (s-1) vs 0.35±0.2 (s-1), p < 0.05) for the RSTLS vs. the two-step method, with the former suggesting that the two-step method was over-regularized. Discussion The proposed RSTLS method provides more realistic measurements of Lagrangian displacement and strain from DENSE images without imposing arbitrary motion models.
Variance Component Testing in Multilevel Models

Available variance component tests are reviewed and three new score tests are presented. In the first score test, the asymptotic normal distribution of the test statistic is used as a reference distribution. In the other two score tests, a Satterthwaite approximation is used for the null distribution of the test statistic. We evaluate the performance of the score tests and other available tests by means of a Monte Carlo study. The new tests are computationally relatively cheap and have good power properties.
Perceived coercion, perceived pressures and procedural justice arising from global lockdowns during the COVID-19 pandemic: A scoping review

This aim of this scoping review is to map what is known about perceived coercion, perceived pressures and procedural justice within the context of the general population’s experience of ‘lockdowns’ imposed by governments worldwide in response to the increased transmission of COVID-19. Arksey & O’Malley’s (2005) framework for conducting scoping reviews was chosen. A sensitive search strategy was devised and conducted using PubMed, Scopus, and Web of Science using the following search terms: (adherence OR acceptance OR agreement OR trust OR distrust OR compliance OR willing*) OR (perceived coerc* OR percept* coerc* OR pressure OR force OR influence OR control OR threat OR justice) AND (lockdown) AND (COVID OR SARS-CoV-2 OR COVID-19). The database search initially produced 41,628 articles to screen. A total of 40 articles were included in this review and the following five themes were identified from the studies: perceived acceptability and willingness to adhere to lockdown; perceived control during lockdown; perceived pressures arising from lockdown; perceived threat of sanction from others and the procedural (in)justice of lockdown. Our synthesis suggests that i) individuals experienced an initial willingness and tolerance of lockdown that lessened over time as perceptions of personal control decreased; ii) that social influences may pressure individuals to follow or break lockdown rules; and iii) that justifiability and proportionality together with individuals’ perceptions of harm from COVID-19 may impact the extent to which individuals adhere to lockdown. Furthermore, the review found an absence of information regarding specific individual characteristics and circumstances that increase the likelihood of experiencing perceived coercion and its related constructs and highlights a need for a better understanding of the cultural and socioeconomic factors affecting perceptions of, and adherence to, lockdown.
Acquired ALK G1202R-, ALK I1171N-, or EML4-ALK-mediated resistance to ensartinib in lung adenocarcinoma but responded to lorlatinib: A case report

ALK rearrangements are identified as driver mutations in non-small-cell lung cancer (NSCLC). EML4 is the most common partner of ALK rearrangements. Here, we reported a patient with lung adenocarcinoma who was identified with EML4-ALK mutations when he progressed on an immune checkpoint inhibitor. The patient was treated with alectinib and obtained a progression-free survival (PFS) of 24 months. Then, next-generation sequencing on circulating tumor DNA identified multiple ALK mutations, including ALK G1202R, I1171N, ALK-ENC1, and EML4-ALK. Ensartinib was given, and the patient achieved a PFS of 5 months. After progression, lorlatinib was administered, and the patient achieved a partial response. Now, the benefit is still ongoing with a PFS over 10 months. Our case may provide evidence for the treatment choice of multiple ALK mutations, including ALK I1171N.
Losing control without your smartphone: Anxiety affects the dynamic choice process of impulsive decision-making and purchase

Different interacting contexts influence the decision-making process, as revealed by the computational modeling. Through four studies, we investigated how smartphone addiction and anxiety influenced impulsive behaviors, along with the underlying psychological mechanisms and dynamic decision-making processes. In the first and second studies, we found no significant correlation between smartphone addiction and impulsive behavior. However, in the third study, we found that smartphone separation increased impulsive decision-making and purchases, and state anxiety, but not trait anxiety, mediated this effect. We explored the dynamic decision-making process using a multi-attribute drift diffusion model (DDM). The results showed that anxiety triggered by smartphone separation changed the trade-offs between decision weights for the fundamental components of the dynamic choice process. In the fourth study, we investigated why smartphone addiction led to increased anxiety and found that extended-self was a mediating factor. Our findings show that smartphone addiction was not correlated with impulsive behaviors, but was correlated with state anxiety in the context of smartphone separation. Further, this study shows how emotional states triggered by different interacting contexts affect the dynamic decision-making process and consumer behaviors.
Amniotic Fluid Disorders: From Prenatal Management to Neonatal Outcomes

Amniotic fluid volume assessment has become standard in the surveillance of fetal well-being, especially in high-risk pregnancies. Amniotic fluid disorders are a frequent and important topic in fetal and perinatal medicine. However, although important advances have been achieved, many important and challenging questions remain unanswered to date. An abnormally low amniotic fluid volume, referred to as oligohydramnios, has been traditionally considered a possible indicator of placental insufficiency or fetal compromise and is associated with an increased rate of obstetric interventions. An excess of amniotic fluid, referred to as polyhydramnios, may be secondary to fetal or maternal conditions and has been associated with a variety of adverse pregnancy outcomes, especially when it is severe. The ultrasonographic detection of an amniotic fluid disorder should prompt a proper workup to identify the underlying etiology. Data on the association of isolated oligohydramnios or idiopathic polyhydramnios with adverse obstetric and perinatal outcomes are conflicting. While the management of secondary oligohydramnios is usually guided by the underlying condition, the management of isolated oligohydramnios is poorly defined. Similarly, the management of idiopathic and secondary polyhydramnios is not yet standardized. There is an urgent need for randomized clinical trials to provide stronger recommendations on the management of these two common conditions.
Sensitivity Analysis of Forecast Errors and the Construction of Optimal Perturbations Using Singular Vectors

Abstract The sensitivity of forecast errors to initial conditions is used to examine the optimality of perturbations constructed from the singular vectors of the tangent propagator of the European Centre for Medium-Range Weather Forecasts model. Sensitivity and pseudo-inverse perturbations based on the 48-h forecast error are computed as explicit linear combinations of singular vectors optimizing total energy over the Northern Hemisphere. It is assumed that these perturbations are close to the optimal perturbation that can be constructed from a linear combination of these singular vectors. Optimality is measured primarily in terms of the medium-range forecast improvement obtained by adding the perturbations a posteriori to the initial conditions. Several issues are addressed in the context of these experiments, including the ability of singular vectors to describe forecast error growth beyond the optimization interval, the number of singular vectors required, and the implications of nonmodal error growth.
Space-time discontinuous Galerkin method for dynamics of solids

In this study, a space–time discontinuous Galerkin formulation is derived for dynamic analysis of solids. Numerical implementation of proposed formulation is presented, and numerical examples are provided for shock wave propagation problems. Numerical results are compared with that of the known exact solutions of the problems and numerical results obtained from a commercial finite element code. The proposed space–time discontinuous Galerkin formulation is found to be robust and successful in modelling transient problems, i.e. shock wave propagation problems. Copyright © 2007 John Wiley & Sons, Ltd.
Are Football Players More Prone to Muscle Injury after COVID-19 Infection? The “Italian Injury Study” during the Serie a Championship

Introduction: Football was the first sport to resume competitions after the coronavirus disease 2019 (COVID-19) lockdown and promptly the hypothesis was raised of a potential relationship between the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and musculoskeletal injuries in athletes. This study aimed to confirm the association between SARS-CoV-2 infection and muscle strain injury in a large population of elite football players and to investigate if the COVID-19 severity level could affect the risk of injury. Methods: A retrospective cohort study involving 15 Italian professional male football teams was performed during the Italian Serie A 2020–2021 season. Injuries and SARS-CoV-2 positivity data were collected by team doctors through an online database. Results: Of the 433 included players, we observed 173 SARS-CoV-2 infections and 332 indirect muscle strains. COVID-19 episodes mostly belonged to severity level I and II. The injury risk significantly increased after a COVID-19 event, by 36% (HR = 1.36, CI95% 1.05; 1.77, p-value = 0.02). The injury burden demonstrated an 86% increase (ratio = 1.86, CI95% 1.21; 2.86, p-value = 0.005) in the COVID-19 severity level II/III versus players without a previous SARS-CoV-2 infection, while level I (asymptomatic) patients showed a similar average burden (ratio = 0.92, CI95% 0.54; 1.58, p-value = 0.77). A significantly higher proportion of muscle–tendon junction injuries (40.6% vs. 27.1%, difference = 13.5%, CI95% 0.002%; 26.9%, p-value = 0.047) was found when comparing level II/III versus Non-COVID-19. Conclusions: This study confirms the correlation between SARS-CoV-2 infection and indirect muscle injuries and highlights how the severity of the infection would represent an additional risk factor.
Theory of the m=1 kink mode in toroidal plasma

The energy principle of ideal magnetohydrodynamics (MHD) is used to study the ideal MHD stability of the m=1 internal kink mode in a toroidal plasma. The equilibrium configurations that are considered allow for a broad region where the safety factor q is close to unity. This region may extend to the magnetic axis, or may be a singular layer. The minimization of the energy functional yields an implicit equation for the growth rate that can be solved by simple numerical means. The examples that are treated numerically retain the essential features of experimentally expected q profiles. The growth rate depends very sensitively on the q profile close to unity and increases with the width of the q≊1 layer. The highest values are of the order of the inverse aspect ratio e divided by the poloidal Alfven time. Nonmonotonic profiles with q>1 on axis are more unstable than monotonic q profiles with q<1. In the latter case, the mode tends to be localized in the q≊1 region instead of in the center.
Phylogenetic relationships of Mycobacterium tuberculosis isolates in Poland: The emergence of Beijing genotype among multidrug-resistant cases

Introduction The epidemiological situation of tuberculosis (TB) in Poland urges for its continuous and scrupulous monitoring. The objective of this study was to explore the genetic diversity of multidrug-resistant (MDR) and drug-susceptible (DS) Mycobacterium tuberculosis isolates from Poland with a combination of spoligotyping and high-resolution mycobacterial interspersed repetitive unit-variable number tandem repeat (MIRU-VNTR) analysis. The results were placed in the Northern and Eastern Europe context. Methods The study included 89 (39 MDR and 50 DS) M. tuberculosis isolates collected from as many patients between 2018 and 2021 in Poland. The analysis was done using spoligotyping, and MIRU-VNTR typing at 24 standard loci. The data were compared to those available on Poland and neighbors and global M. tuberculosis datasets. Results The main identified families were Beijing (28.1%) and Haarlem (16.8%) while 34.8% of isolates were in the heterogeneous L4-unclassified group. Although the Beijing family was the most prevalent (61.5%) among MDR-TB cases, it accounted for only 2% of DS isolates. Among foreign-born patients, a higher ratio of MDR isolates were observed when compared with those who Poland-born (64.3% vs. 40%). Furthermore, all patients from the Former Soviet Union (FSU) countries were infected with MDR-TB. Discussion Whereas DS M. tuberculosis population in Poland is dominated by L4 isolates, MDR isolates are mostly of the Beijing genotype. The rise in the prevalence of the Beijing isolates in Poland, coupled with high proportion of the Beijing genotype among foreign-born TB patients may reflect an ongoing transmission of this family, imported to Poland mainly from FSU countries.
Alternative splicing in ABA signaling during seed germination

Seed germination is an essential step in a plant’s life cycle. It is controlled by complex physiological, biochemical, and molecular mechanisms and external factors. Alternative splicing (AS) is a co-transcriptional mechanism that regulates gene expression and produces multiple mRNA variants from a single gene to modulate transcriptome diversity. However, little is known about the effect of AS on the function of generated protein isoforms. The latest reports indicate that alternative splicing (AS), the relevant mechanism controlling gene expression, plays a significant role in abscisic acid (ABA) signaling. In this review, we present the current state of the art about the identified AS regulators and the ABA-related changes in AS during seed germination. We show how they are connected with the ABA signaling and the seed germination process. We also discuss changes in the structure of the generated AS isoforms and their impact on the functionality of the generated proteins. Also, we point out that the advances in sequencing technology allow for a better explanation of the role of AS in gene regulation by more accurate detection of AS events and identification of full-length splicing isoforms.
Synthesis and Biological Evaluation of Coumarin Triazoles as Dual Inhibitors of Cholinesterases and β-Secretase

Coumarin is a naturally occurring bioactive pharmacophore with wide occurrence among central nervous system (CNS)-active small molecules. 8-Acetylcoumarin, one of the natural coumarins, is a mild inhibitor of cholinesterases and β-secretase, which are vital targets of Alzheimer’s disease. Herein, we synthesized a series of coumarin–triazole hybrids as potential multitargeted drug ligands (MTDLs) with better activity profiles. The coumarin–triazole hybrids occupy the cholinesterase active site gorge from the peripheral to the catalytic anionic site. The most active analogue, 10b, belonging to the 8-acetylcoumarin core, inhibits acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and β-secretase-1 (BACE-1) with IC50 values of 2.57, 3.26, and 10.65 μM, respectively. The hybrid, 10b, crosses the blood–brain barrier via passive diffusion and inhibits the self-aggregation of amyloid-β monomers. The molecular dynamic simulation study reveals the strong interaction of 10b with three enzymes and forming stable complexes. Overall, the results warrant a detailed preclinical investigation of the coumarin–triazole hybrids.