Miracle-dz/UniFAR-FTUs huggingface dataset:
Characteristics of the Online Market for Anabolic-Androgenic Steroids in Central Asia: A Netnographic Analysis

Abstract Background: With the online proliferation of illegal substances, the Internet offers a wide variety of information on the acquisition and intake of anabolic-androgenic steroids (AAS) and other performance and image enhancing drugs. This study focuses on investigating the characteristics of the online AAS market in Central Asia. Objectives: The primary objectives of this study were to investigate the accessibility and features of the online market for AAS in Central Asia. To achieve this, we employed a netnographic approach for a systematic exploration of websites advertising and selling AAS. The study aimed to conduct a comprehensive analysis of several key aspects, including the variety of AAS products offered, the quality of health advice provided the level of product availability, the procedures involved in making purchases, and the pricing structures within this market. Results: Twenty-one websites supplying AAS in Central Asia met our inclusion criteria. Using content analysis, data were gathered on AAS offerings, quality of health advice provided, availability, purchase process, and prices. Data were synthesized using descriptive statistics. Results indicate that AAS are easily accessible for purchase without valid medical prescription in the Central Asia online market. Most websites advertised the aesthetic and ergogenic benefits of AAS use without indicating the potential complications and adverse effects. Conclusions: Public health efforts to mitigate AAS use in Central Asia should consider both the online accessibility of AAS and the lack of accompanying information on potential complications as well as adverse effects associated with their use. Efforts must be intensified to curtail the proliferation of AAS and related misleading information on the Central Asian online market.
Analysis of the adverse events following the mRNA-1273 COVID-19 vaccine

ABSTRACT Objective This study aims to characterize the adverse events (AEs) following the administration of the mRNA-1273 COVID-19 vaccine from the Vaccine Adverse Event Reporting System (VAERS) data. Methods In this case/non-case analysis, reports between 1 January 2021, and 27 October 2022, were extracted from VAERS. AEs were defined as preferred terms (PTs) by Medical Dictionary for Regulatory Activities (MedDRA) terminology. Disproportionality analyses were conducted to calculate the reporting odds and proportional reporting ratios. The Bayesian approach was used to calculate information component (IC) values and Empirical Bayesian Geometric Mean scores for all the AEs detected. Results 186 MedDRA PTs compromising 702,495 AEs associated with the mRNA-1273 vaccine were identified. Three statistically significant signals were identified for general and systemic AEs, administration site conditions, and product issues. Cardiac disorders were rarely reported, the most common being; 489 reports for ‘myocarditis’ (19.44%), 475 for ‘acute myocardial infarction’ (18.88%), 457 for ‘myocardial infarction’ (18.16%), 290 for ‘bradycardia’ (11.53%) and 281 for ‘pericarditis’ (11.17%). Conclusions The most frequently identified AEs following mRNA-1273 vaccination agree with those listed within the Summary of Product Characteristics. In addition, disproportionality analysis did not find any statistically significant signals for myocarditis or pericarditis.
Sparse clustered inhibition projects sequential activity onto unique neural subspaces

Neural activity in the brain traces sequential trajectories on low dimensional subspaces. For flexible behavior, these neural subspaces must be manipulated and reoriented within tens of milliseconds. Using mathematical analysis and simulation of a recurrently connected neural circuit for sequence generation, we report that incorporating a subtype of interneurons that provides sparse but clustered inhibition enables the projection of sequential activity onto task- or context-specific neural subspaces. Depending on the sparsity of inhibitory projections, neural subspaces could be arbitrarily rotated with respect to the intrinsic subspace, without altering the key aspects of sequence generation. Thus, we propose a circuit motif and mechanism by which inhibitory interneurons can enable flexible switching between neural subspaces on a fast timescale of milliseconds, controlled by top down signals. Significance Statement Cognitive faculties like memory, movement, and decision-making depend on the reliable sequential activation of neurons in the brain. These activity sequences reside on low dimensional neural subspaces, with different tasks or behaviors represented on different subspaces. Flexible cognition therefore requires changes in subspace orientation on timescales as fast as tens of milliseconds. Here we propose a mechanism for fast timescale control of the neural subspace in a recurrently connected neural network model for sequence generation. Subspace manipulation is implemented by inhibitory neurons that form sparse, clustered axonal projections onto the neurons responsible for sequence generation. Ensembles of these inhibitory neurons rapidly rotate the neural subspace and support storage of and dynamical switching between neural activity sequences on low dimensional manifolds.
Comparative cardiotoxicity assessment of bisphenol chemicals and estradiol using human induced pluripotent stem cell-derived cardiomyocytes

Background Bisphenol A (BPA) is commonly used to manufacture consumer and medical-grade plastics. Due to health concerns, BPA substitutes are being incorporated – including bisphenol S (BPS) and bisphenol F (BPF) – without a comprehensive understanding of their toxicological profile. Objective Previous studies suggest that bisphenol chemicals perturb cardiac electrophysiology in a manner that is similar to 17β-estradiol (E2). We aimed to compare the effects of E2 with BPA, BPF, and BPS using human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM). Methods Cardiac parameters were evaluated using microelectrode array (MEA) technology and live-cell fluorescent imaging at baseline and in response to chemical exposure (0.001-100 μM). Results Cardiac metrics remained relatively stable after exposure to nanomolar concentrations (1-1,000 nM) of E2, BPA, BPF, or BPS. At higher micromolar concentrations, chemical exposures resulted in a decrease in the depolarizing spike amplitude, shorter field potential and action potential duration, shorter calcium transient duration, and decrease in hiPSC-CM contractility (E2 > BPA > BPF >> BPS). Cardiomyocyte physiology was largely undisturbed by BPS exposure. BPA-induced effects were exaggerated when co-administered with an L-type calcium channel antagonist (verapamil) or E2 - and reduced when co-administered with an L-type calcium channel agonist (Bay K8644) or an estrogen receptor alpha antagonist (MPP). E2-induced effects generally mirrored those of BPA, but were not exaggerated by co-administration with an L-type calcium channel antagonist. Discussion Collectively across multiple cardiac endpoints, E2 was the most potent and BPS was the least potent disruptor of hiPSC-CM function. Although the observed cardiac effects of E2 and BPA were similar, a few distinct differences suggest that these chemicals may act (in part) through different mechanisms. hiPSC-CM are a useful model for screening cardiotoxic chemicals, nevertheless, the described in vitro findings should be validated using a more complex ex vivo and/or in vivo model.
The HOMEODOMAIN-Like protein HDL mediates chromatin organization and rewires leaf epidermal patterning

The Arabidopsis leaf epidermis is comprised of trichomes, pavement cells, and stomata, originating from versatile precursor cells capable of dividing or differentiating to create unique epidermal patterns. The mechanism governing these transitions and the maintenance of cell heterogeneity remains unclear. In this study, we identified a novel homeodomain-like superfamily protein, HDL, localized in chromocenters and playing a role in chromatin organization. HDL interacts with histone deacetylase 6 (HDA6) and methyltransferases, indicating its function in modulating chromatin accessibility. In hdl mutants, we observed moderately increased chromatin accessibility in the promoter region of protein-coding genes, along with reduced stomatal density and elevated trichome numbers on leaf surfaces. Corresponding to these phenotypes, stomatal-related gene expression decreased, while a transcriptional reporter for GLABRA2, a trichome initiation gene, exhibited higher and more variable expression levels. These findings highlight how HDL-mediated chromatin organization influences epidermal cell fate by modulating gene expression and enhancing cell heterogeneity within the leaf epidermis. One Sentence Summary A homeodomain-like protein functions with histone modifiers to regulate chromatin and influence cell fate decisions.
Pharmacokinetic and Pharmacodynamic Effects of Polyclonal Antibodies against SARS-CoV2 in Mice

Despite ongoing vaccination efforts to prevent SARS-CoV-2 infections, treatment tools are still necessary to address the ongoing COVID-19 pandemic. We report here that COVID-HIGIV, a human immunoglobulin product for treatment of COVID-19, provided a significant survival benefit in SARS-CoV-2 infected transgenic mice compared to controls. COVID-HIGIV also has similar pharmacokinetic profiles in healthy and SARS-CoV-2 infected mice over time after intravenous administration, with identical or comparable Tmax, Cmax, AUC0–∞ and Cl. AUC0–last increased and mean residence time, T1/2, and Vd reduced in infected animals compared to healthy animals. These data suggest that COVID-HIGIV may be an effective treatment for SARS-CoV-2 infection when given early after exposure.
Convection naturelle MHD dans une cavité horizontale élancée

Lors de la croissance des monocristaux semi-conducteurs a partir d'un bain fondu, la convection naturelle gouverne de maniere determinante les transferts de masse et de chaleur. Comme la micro-gravite, l'imposition d'un champ magnetique permanent sur le bain - electro-conducteur - est un moyen de stabiliser, de reorganiser l'ecoulement de convection naturelle et, finalement, de le freiner afin de s'approcher au mieux des conditions ideales d'un transport diffusif des especes chimiques. Dans un premier temps, une synthese des connaissances acquises sur les ecoulements thermogravitaires, magnetohydrodynamiques (mhd) ou non, est presentee. Puis, sur la base du dispositif experimental mascot (magnetic stabilisation of convection and turbulence), les phenomenes qui gouvernent l'ecoulement thermogravitaire mhd du mercure dans une cavite cylindrique horizontale elancee, soumise a la fois a un champ magnetique uniforme et a un gradient de temperature horizontal, sont mis en evidence puis interpretes a l'aide de la mhd. Dans cette configuration particuliere, les couches de hartmann demeurent electriquement inactives. L'inertie n'influence l'ecoulement que localement (aux extremites de la cavite), et surtout dans le cas ou la convection est intense (a grand nombre de grashoff). Ailleurs, le couplage entre courants electriques induits et distribution de temperature est illustre par l'equilibre entre le rotationnel de la force de laplace et le rotationnel de la force de flottabilite. Cet equilibre pilote l'ecoulement pour un nombre de rayleigh modifie, dit effectif, suffisamment faible. Une simulation numerique 3-d aux elements finis de cet ecoulement (laminaire) apporte une confirmation satisfaisante de ces resultats experimentaux. Ce memoire est l'etude de la transition de cet ecoulement vers la turbulence, a l'aide de l'experience mascot. Trois ondes oscillantes progressives ou stationnaires sont clairement identifiees pendant la transition. Si la convention est intense, ces ondes interagissent avec des instabilites stationnaires evoluant faiblement dans le temps. Le couplage non-lineaire associe au terme de convection dans l'equation de l'energie engendre une bifurcation sous-critique. Puis, si le regime d'ecoulement est faiblement convectif, le chaos survient a la suite d'une bifurcation supercritique de hopf. Ces resultats ouvrent des perspectives de developpement technologique pour le procede bridgman de croissance cristalline. Et plus generalement, ce progres dans la comprehension de la convection naturelle mhd pourrait s'appliquer dans d'autres situations: en genie metallurgique ou dans les couvertures tritigenes du futur reacteur de fusion thermonucleaire
The West Spitsbergen Current: Transport, Forcing, and Variability.

Abstract : The West Spitsbergen Current is commonly considered to be the northern extension of the Norwegian Atlantic Current, and it forms one of the branches of the circulation pattern of the Greenland-Norwegian sea system. It flows northward along the continental margin west of Spitsbergen, entering the Arctic basin on the east side of the Greenland-Spitsbergen passage (Fram Strait). Previous work (Aagaard and Greisman, 1975) has shown that it provides the major component in the mass and heat balances of the Polar Basin. Beginning in summer 1976, moored current and temperature recorders have been deployed in the WSC at 79 N, and the data records from 1976-79 and 1980-81 provide the basis for this work. The data have been used to estimate the volume and heat transports by the current and to define the structure and variability of the flow. In addition to the presentation of basic results, there is a discussion of the dynamics of the current with emphasis on explaining the length and time scales of the observed variability and on ascertaining the nature of the forces driving the flow.
A novel imaging method (FIM-ID) reveals that myofibrillogenesis plays a major role in the mechanically induced growth of skeletal muscle

An increase in mechanical loading, such as that which occurs during resistance exercise, induces radial growth of muscle fibers (i.e. an increase in cross-sectional area). Muscle fibers are largely composed of myofibrils, but whether radial growth is mediated by an increase in the size of the myofibrils (i.e. myofibril hypertrophy) and/or the number of myofibrils (i.e. myofibrillogenesis) is not known. Electron microscopy (EM) can provide images with the level of resolution that is needed to address this question, but the acquisition and subsequent analysis of EM images is a time- and cost-intensive process. To overcome this, we developed a novel method for visualizing myofibrils with a standard fluorescence microscope (fluorescence imaging of myofibrils with image deconvolution [FIM-ID]). Images from FIM-ID have a high degree of resolution and contrast, and these properties enabled us to develop pipelines for automated measurements of myofibril size and number. After extensively validating the automated measurements, we used both mouse and human models of increased mechanical loading to discover that the radial growth of muscle fibers is largely mediated by myofibrillogenesis. Collectively, the outcomes of this study offer insight into a fundamentally important topic in the field of muscle growth and provide future investigators with a time- and cost-effective means to study it.
Mate choice in the brain: Species differ in how male traits ‘turn on’ gene expression in female brains

Mate choice plays a fundamental role in speciation, yet we know little about the molecular mechanisms that underpin this crucial decision-making process. Female stickleback fish differentially adapted to limnetic and benthic habitats and considered members of reproductively isolated species use different male traits to evaluate prospective partners and reject heterospecific males. Here, we integrate behavioral data from a mate choice experiment involving benthic and limnetic fish with gene expression data from the brains of females making these mate choice decisions. We find substantial gene expression variation between limnetic and benthic species, regardless of behavioral context, suggesting general divergence in gene expression patterns in female brains, in accordance with their genetic differentiation. Intriguingly, female gene co-expression modules covary with male display traits but in opposing directions for sympatric populations of the two species, suggesting male displays elicit a genomic response that reflects known differences in female preferences which serve to isolate the species. Furthermore, our analysis confirms the role of numerous candidate genes previously implicated in female mate choice decision-making in other teleost species, suggesting that these cognitive molecular processes are, in part, evolutionarily conserved. Taken together, our study adds important new insights to our understanding of the molecular processes underlying female decision-making that maintain isolation between diverging species.
Magnetically Powered Microwheel Thrombolysis of Occlusive Thrombi in Zebrafish

Tissue plasminogen activator (tPA) is the only FDA approved treatment for ischemic stroke but carries significant risks, including major hemorrhage. Additional options are needed, especially in small vessel thrombi which account for ∼25% of ischemic strokes. We have previously shown that tPA-functionalized colloidal microparticles can be assembled into microwheels (µwheels) and manipulated under the control of applied magnetic fields to enable rapid thrombolysis of fibrin gels in microfluidic models of thrombosis. Providing a living microfluidic analog, transparent zebrafish larvae have a highly conserved coagulation cascade that enables studies of hemostasis and thrombosis in the context of intact vasculature, clotting factors, and blood cells. Here we show that tPA-functionalized µwheels can perform rapid and targeted recanalization in vivo. This effect requires both tPA and µwheels, as minimal to no recanalization is achieved with tPA alone, µwheels alone, or tPA-functionalized microparticles in the absence of a magnetic field. We evaluated tPA-µwheels in CRISPR-generated plasminogen (plg) heterozygous and homozygous mutants and confirmed that tPA-µwheels are dose-dependent on plasminogen for lysis. We have found that magnetically powered µwheels as a targeted tPA delivery system are dramatically more efficient at plasmin-mediated thrombolysis than systemic delivery in vivo. Further development of this system in fish and mammalian models could enable a less invasive strategy for alleviating ischemia that is safer than directed thrombectomy or systemic infusion of tPA.
Kinematic performance declines as group size increases during escape responses in a schooling coral reef fish

Escaping predation is essential for species survival, but prey must effectively match their response to the perceived threat imposed by a predator. For social animals, one mechanism to reduce risk of predation is living in larger group sizes, which dilutes each individual’s risk of capture. When a predator attacks, individuals from a range of taxa (e.g., fishes, sharks, amphibians) perform an escape response, to evade the attack. Here, using the schooling coral reef damselfish Chromis viridis, we assess if there is an optimal group size that maximizes both individual escape response performance as well as group cohesion and coordination following a simulated predator attack, comparing schools composed of four, eight, and sixteen fish. We found that fish in various group sizes exhibited no difference in their reaction timing to a simulated predator attack (i.e., escape latency), but larger groups exhibited slower kinematics (i.e., lower average turning rate and shorter distance covered during the escape response), potentially because larger groups perceived the predator attack as less risky due to safety in numbers. Both school cohesion and coordination (as measured through alignment and nearest neighbor distance, respectively) declined in the 100ms after the predator’s attack. While there was no impact of group size on alignment, larger group sizes exhibited closer nearest neighbor distances at all times. This study highlights that larger group sizes may allow individuals to save energy on costly behavioral responses to avoid predators, potentially through a greater threshold of the threat necessary to trigger a rapid escape response.
Resource Strategies of Wild Plants

Over millions of years, terrestrial plants have competed for limited resources, defended themselves against herbivores, and resisted a myriad of environmental stresses. These struggles have helped generate more than a quarter million terrestrial plant species, each possessing a unique strategy for success. Yet, as Resource Strategies of Wild Plants demonstrates, the constraints on plant growth are universal enough that a few survival strategies hold true for all seed-producing plants. This book describes the five major strategies of growth for terrestrial plants, details how plants succeed when resources are scarce, delves into the history of research into plant strategies, and resets the foundational understanding of ecological processes. Drawing from recent findings in plant-herbivore interactions, ecosystem ecology, and evolutionary ecology, Joseph Craine explains how plants attain available nutrients, withstand the immense stresses of drying soils, and flourish in the race for light. He shows that the competition for resources has shaped plant evolution in newly discovered ways, while the scarcity of such resources has affected how plants interact with herbivores, wind, fire, and frost. An understanding of the major resource strategies of wild plants remains central to learning about the ecology of plant communities, global changes in the biosphere, methods for species conservation, and the evolution of life on earth.
Interaction between task-evoked and spontaneous brain activities: Insights from two event-related fMRI studies

Human brain activities measured by fMRI can be categorized into at least two distinct categories; 1) spontaneous: slow (< 0.1 Hz) but inter-regionally coherent fluctuations in MR signal, and 2) task-evoked: change in the MR signal due to external stimulation. To date, there is no consensus in the field about the roles of spontaneous brain activity and whether it interacts with task-evoked activity. This is mainly because direct measurements of spontaneous activity during task performance is challenging, if not impossible. Here for the first time, we used a data-driven approach to obtain the time course of the spontaneous brain activity in two of the well-studied brain networks; 1) the Default mode network (DMN), where the strongest task-evoked negative BOLD response is also observed and 2) the dorsal attention network (DAN), where some of the strongest task-evoked positive BOLD response is observed. Voxel-wise multiple regression analysis is used to model fMRI timeseries with anticipated task-evoked BOLD response, the obtain time course of the spontaneous activity, and their interaction at each participant. Using 46 young and cognitively normal participants performing an event-related perceptual speed task inside the fMRI scanner, we showed that there is no significant interaction between the spontaneous and the task-evoked activity either as negative BOLD response in the DMN or as positive BOLD response in the DAN. We replicate our findings in a separate dataset with 24 young and cognitively normal participants performing a different event-related task inside another fMRI scanner. Our results suggest that the presence or absence of coherent spontaneous activity in the DMN, or DAN has negligible effect on the magnitude of the BOLD response and vice versa, which consequently means that the fMRI signal is a linear superposition of spontaneous and task evoked activity.