Miracle-dz/UniFAR-FTUs huggingface dataset:
Transcriptional heterogeneity and tightly regulated changes in gene expression during Plasmodium berghei sporozoite development

Significance A better understanding of the molecular mechanisms underlying the development of Plasmodium parasites in Anopheles mosquitoes would facilitate the development of malaria vaccines and of novel strategies to interrupt disease transmission. We characterized, at the single-cell level, the gene expression profiles of sporozoites from the rodent malaria parasite Plasmodium berghei, throughout their development in mosquitoes and upon salivation. Our analyses reveal heterogeneity in gene expression among parasites isolated from the same anatomical location, suggesting that parasite development is asynchronous in mosquitoes. In addition, our results highlight the role of gene expression changes in regulating the ability of sporozoites to remain quiescent in the salivary glands, and their rapid reactivation upon salivation. Despite the critical role of Plasmodium sporozoites in malaria transmission, we still know little about the mechanisms underlying their development in mosquitoes. Here, we use single-cell RNA sequencing to characterize the gene expression profiles of 16,038 Plasmodium berghei sporozoites isolated throughout their development from midgut oocysts to salivary glands, and from forced salivation experiments. Our results reveal a succession of tightly regulated changes in gene expression occurring during the maturation of sporozoites and highlight candidate genes that could play important roles in oocyst egress, sporozoite motility, and the mechanisms underlying the invasion of mosquito salivary glands and mammalian hepatocytes. In addition, the single-cell data reveal extensive transcriptional heterogeneity among parasites isolated from the same anatomical site, suggesting that Plasmodium development in mosquitoes is asynchronous and regulated by intrinsic as well as environmental factors. Finally, our analyses show a decrease in transcriptional activity preceding the translational repression observed in mature sporozoites and associated with their quiescent state in salivary glands, followed by a rapid reactivation of the transcriptional machinery immediately upon salivation.
Adolescent social networks matter for suicidal trajectories: disparities across race/ethnicity, sex, sexual identity, and socioeconomic status

Abstract Background Examining social networks, characterized by interpersonal interactions across family, peer, school, and neighborhoods, offer alternative explanations to suicidal behaviors and shape effective suicide prevention. This study examines adolescent social networks predicting suicide ideation and attempt trajectories transitioning to adulthood, while revealing differences across racial/ethnic, sex, sexual identity, and socioeconomic status. Methods Participants included 9421 high school students (Mage = 15.30 years; 54.58% females, baseline) from Waves I–IV of the National Longitudinal Study of Adolescent to Adult Health, 1994–2008. Latent class growth analyses were conducted to identify suicide ideation and attempt trajectories. Multivariate multinomial logistic regressions examined the relationships between social network characteristics during adolescence and suicidal trajectories. Interaction terms between social networks and sociodemographic characteristics were included to test moderation effects. Results Three suicidal ideation trajectories (low-stable, high-decreasing, moderate-decreasing-increasing) and two suicide attempt trajectories (low-stable, moderate-decreasing) were identified. Greater family cohesion significantly reduced the probability of belonging to high-decreasing (Trajectory 2) and moderate-decreasing-increasing (Trajectory 3) suicidal ideation trajectories, and moderate-decreasing (Trajectory 2) suicide attempt trajectory. Race/ethnicity, sex, and sexual identity significantly moderated the associations between social networks (household size, peer network density, family cohesion, peer support, neighborhood support) and suicidal trajectories. Conclusions Social networks during adolescence influenced the odds of belonging to distinct suicidal trajectories. Family cohesion protected youth from being in high-risk developmental courses of suicidal behaviors. Social networks, especially quality of interactions, may improve detecting adolescents and young adults at-risk for suicide behaviors. Network-based interventions are key to prevent suicidal behaviors over time and suicide intervention programming.
Molecular mechanisms of inhibitor bindings to A-FABP deciphered by using molecular dynamics simulations and calculations of MM-GBSA

ABSTRACT Adipocyte fatty-acid binding protein (A-FABP) plays a central role in many aspects of metabolic diseases. It is an important target in drug design for treatment of FABP-related diseases. In this study, molecular dynamics (MD) simulations followed by calculations of molecular mechanics generalized Born surface area (MM-GBSA) and principal components analysis (PCA) were implemented to decipher molecular mechanism correlating with binding of inhibitors 57Q, 57P and L96 to A-FABP. The results show that van der Waals interactions are the leading factors to control associations of 57Q, 57P, and L96 with A-FABP, which reveals an energetic basis for designing of clinically available inhibitors towards A-FABP. The information from PCA and cross-correlation analysis rationally unveils that inhibitor bindings affect conformational changes of A-FABP and change relative movements between residues. Decomposition of binding affinity into contributions of individual residues not only detects hot spots of inhibitor/A-FABP binding but also shows that polar interactions of the positively charged residue Arg126 with three inhibitors provide a significant contribution for stabilization of the inhibitor/A-FABP bindings. Furthermore, the binding strength of L96 to residues Ser55, Phe57 and Lys58 are stronger than that of inhibitors 57Q and 57P to these residues.
Immersive virtual reality and digital applied gaming interventions for the treatment of mental health problems in children and young people: the need for rigorous treatment development and clinical evaluation.

BACKGROUND Mental health problems in children and young people are common and can lead to poor long-term outcomes. Despite the availability of effective psychological interventions for mental health disorders, only a minority of affected children and young people access treatment. Digital interventions, such as applied games and virtual reality (VR), that target mental health problems in children and young people may hold a key to increasing access to, engagement with, and potentially the effectiveness of psychological treatments. To date, several applied games and VR interventions have been specifically developed for children and young people. This systematic review aims to identify and synthesize current data on the experience and effectiveness of applied games and VR for targeting mental health problems in children and young people (defined as average age of 18 years or below). METHODS Electronic systematic searches were conducted in Medline, PsycINFO, CINAHL, and Web of Science. RESULTS Nineteen studies were identified that examined nine applied games and two VR applications, and targeted symptoms of anxiety, depression, and phobias using both quantitative and qualitative methodologies. Existing evidence is at a very early stage and studies vary extensively in key methodological characteristics. For applied games, the most robust evidence is for adolescent depressive symptoms (medium clinical effect sizes). Insufficient research attention has been given to the efficacy of VR interventions in children and young people. CONCLUSIONS The evidence to date is at a very early stage. Despite the enthusiasm for applied games and VR, existing interventions are limited in number and evidence of efficacy, and there is a clear need for further co-design, development, and evaluation of applied games and VR before they are routinely offered as treatments for children and young people with mental health problems.
The Potential Relevance of the Microbiome to Hair Physiology and Regeneration: The Emerging Role of Metagenomics

Human skin and hair follicles are recognized sites of microbial colonization. These microbiota help regulate host immune mechanisms via an interplay between microbes and immune cells, influencing homeostasis and inflammation. Bacteria affect immune responses by controlling the local inflammatory milieu, the breakdown of which can result in chronic inflammatory disorders. Follicular microbiome shifts described in some inflammatory cutaneous diseases suggest a link between their development or perpetuation and dysbiosis. Though the hair follicle infundibulum is an area of intense immunological interactions, bulb and bulge regions represent immune-privileged niches. Immune privilege maintenance seems essential for hair growth and regeneration, as collapse and inflammation characterize inflammatory hair disorders like alopecia areata and primary cicatricial alopecia. Current research largely focuses on immunological aberrations. However, studies suggest that external stimuli and interactions across the follicular epithelium can have profound effects on the local immune system, homeostasis, and cycling. Herein, we review hair follicle bacterial colonization, its possible effects on the underlying tissue, and links to the pathogenesis of alopecia, beyond the pure investigation of specific species abundance. As skin microbiology enters the metagenomics era, multi-dimensional approaches will enable a new level of investigations on the effects of microorganisms and metabolism on host tissue.
Acceptability, Safety, and Resonance of the Pilot Digital Suicide Prevention Campaign “Better Off With You”: Qualitative Study

Background The Interpersonal Theory of Suicide posits that there are three key elements of suicidal behavior: perceived burdensomeness, thwarted belongingness, and the acquired capability for suicide. The digital campaign Better Off With You was developed to directly challenge the idea of perceived burdensomeness among people who are contemplating suicide in 2 communities within Australia. Objective The aim of this study is to explore the needs and preferences of people with lived experience of suicidal thoughts and actions to inform the development of Better Off With You. Methods This study involved a series of focus groups that aimed to discuss campaign messaging, scope, and approach. People with lived experience of suicidal thoughts and actions attended the focus groups. After the completion of initial focus groups, the results informed the creation of campaign collateral by creative agencies. Early versions of the campaign collateral were then presented in the user testing sessions. Transcriptions were analyzed via thematic analysis. Results In total, 13 participants attended the focus groups and 14 attended the user testing sessions. The following three overarching themes were presented: acceptability, safety, and resonance. Participants believed that suicide is a serious and ongoing issue in their communities and welcomed a localized suicide prevention focus via peer-to-peer storytelling. The idea of perceived burdensomeness required clarification but was perceived as acceptable and relevant. Participants seemed drawn toward peer narratives that they perceived to be authentic, genuine, and believable as given by real people with lived experience. Campaign messaging needs to be clear and empathetic while directly talking about suicide. Participants did not anticipate any significant negative or harmful impact from any campaign videos and highlighted the importance of providing appropriate help-seeking information. Conclusions This iterative study provided important insights and knowledge about peer-to-peer storytelling in suicide prevention campaigns. Future campaigns should involve simple messaging, be validating and empathetic, and consider including a lived experience perspective.
Diaminopyridazine aus Diaminocyclopropenyliumsalzen und (Diazomethyl)- Verbindungen

Diaminocyclopropenyliumsalze (14a,b) reagieren in Dichloromethan mit den phosphorylierten Diazomethanen 15a-e in Gegenwart von Ethyl-diisopropylamin bzw. 1,5-Diazabicyclo[4.3. 0]non-5-en spezifisch zu den 4,5-Diaminopyridazinen 16a-f. Aus dem Salz 14c und den Diazomethylverbindungen 15a,c,d sowie f-k in Dichlormethan im Beisein der bicyclischen Base bilden sich dagegen die 3,4-Diaminopyridazine 17a-i. In mechanistischer Hinsicht ist die Bildung intermediar auftretender (Diazomethyl)cyclopropene (14a,b + 15 18) bzw. (14c + 15 19) im Sinne der elektrophilen Diazoalkansubstitution zu interpretieren; weder 18, noch 19 lassen sich isolieren, sondern gehen eine rasche [1,5]-Cyclisierung zu den Betainen 20 bzw. 21 ein, die abschliesend durch Offnung der Bruckenbindung zu den Pyridazinen 16 bzw. 17 isomerisieren. Diaminocyclopropenylium salts 14a,b react specifically with the phosphorylated diazomethanes 15a-e in dichloromethane in the presence of ethyl diisopropylamine and 1,5-diazabicyclo[4.3. 0]non-5-ene respectively to the 4,5-diaminopyridazines 16a-f. In contrast to that the 3,4-diaminopyridazines 17a-i are formed in the reaction of the salt 14c with the diazomethyl compounds 15a,c,d such as f-k in dichloromethane in the presence of the bicyclic base. With regard to the reaction mechanism the formation of the intermediate diazomethyl cyclopropenes (14a,b + 15 18 or 14c + 15 19) has to be interpreted in the sense of an electrophilic diazoalkane substitution reaction; neither 18 nor 19 can be isolated but undergo a fast [1,5]-cyclization to the betaines 20 or 21, which finally isomerize to the pyridazines 16 or 17 by opening of the bridge bond.
Tuning Mg(OH)2 Structural, Physical, and Morphological Characteristics for Its Optimal Behavior in a Thermochemical Heat-Storage Application

Thermochemical materials (TCM) are among the most promising systems to store high energy density for long-term energy storage. To be eligible as candidates, the materials have to fit many criteria such as complete reversibility of the reaction and cycling stability, high availability of the material at low cost, environmentally friendliness, and non-toxicity. Among the most promising TCM, the Mg(OH)2/MgO system appears worthy of attention for its properties in line with those required. In the last few decades, research focused its attention on the optimization of attractive hydroxide performance to achieve a better thermochemical response, however, often negatively affecting its energy density per unit of volume and therefore compromising its applicability on an industrial scale. In this study, pure Mg(OH)2 was developed using different synthesis procedures. Reverse deposition precipitation and deposition precipitation methods were used to obtain the investigated samples. By adding a cationic surfactant (cetyl trimethylammonium bromide), deposition precipitation Mg(OH)2 (CTAB-DP-MH) or changing the precipitating precursor (N-DP-MH), the structural, physical and morphological characteristics were tuned, and the results were compared with a commercial Mg(OH)2 sample. We identified a correlation between the TCM properties and the thermochemical behavior. In such a context, it was demonstrated that both CTAB-DP-MH and N-DP-MH improved the thermochemical performances of the storage medium concerning conversion (64 wt.% and 74 wt.% respectively) and stored and released heat (887 and 1041 kJ/kgMg(OH)2). In particular, using the innovative technique not yet investigated for thermal energy storage (TES) materials, with NaOH as precipitating precursor, N-DP-MH reached the highest stored and released heat capacity per volume unit, ~684 MJ/m3.
Differential Response of Lung Cancer Cells, with Various Driver Mutations, to Plant Polyphenol Resveratrol and Vitamin D Active Metabolite PRI-2191

Plant polyphenols and vitamins D exhibit chemopreventive and therapeutic anticancer effects. We first evaluated the biological effects of the plant polyphenol resveratrol (RESV) and vitamin D active metabolite PRI-2191 on lung cancer cells having different genetic backgrounds. RESV and PRI-2191 showed divergent responses depending on the genetic profile of cells. Antiproliferative activity of PRI-2191 was noticeable in EGFRmut cells, while RESV showed the highest antiproliferative and caspase-3-inducing activity in KRASmut cells. RESV upregulated p53 expression in wtp53 cells, while downregulated it in mutp53 cells with simultaneous upregulation of p21 expression in both cases. The effect of PRI-2191 on the induction of CYP24A1 expression was enhanced by RESV in two KRASmut cell lines. The effect of RESV combined with PRI-2191 on cytokine production was pronounced and modulated. RESV cooperated with PRI-2191 in regulating the expression of IL-8 in EGFRmut cells, while OPN in KRASmut cells and PD-L1 in both cell subtypes. We hypothesize that the differences in response to RESV and PRI-2191 between EGFRmut and KRASmut cell lines result from the differences in epigenetic modifications since both cell subtypes are associated with the divergent smoking history that can induce epigenetic alterations.
Spectro-temporal Studies of Rapid Transition of the Quasi-periodic Oscillations in the Black Hole Source H1743-322

An appearance or disappearance of quasi-periodic oscillations (QPOs) associated with the variation of X-ray flux can be used to decipher the accretion–ejection mechanism of black hole X-ray sources. We searched for and studied such rapid transitions in H1743-322 using archival data from the Rossi X-ray Timing Explorer and found eight such events, where a QPO vanishes suddenly along with the variation of X-ray flux. The appearance/disappearance of QPOs was associated with four events exhibiting type-B QPOs at ∼4.5 Hz: one was a type-A QPO at ν ∼ 3.5 Hz, and the other three were connected to type-C QPOs at ∼9.5 Hz. Spectral studies of the data revealed that the inner disk radius remained at the same location around 2–9 r g , depending on the model used, but power-law indices were varying, indicating that either a corona or a jet is responsible for the events. The probable ejection radii of coronas were estimated to be around 4.2–15.4 r g based on the plasma ejection model. Our X-ray and quasi-simultaneous radio correlation studies suggest that the type-B QPOs are probably related to the precession of a weak jet, though a small and weak corona is present at its base, and the type-C QPOs are associated with the base of a relatively strong jet, which is acting like a corona.
Astrophysics & cosmology from line intensity mapping vs galaxy surveys

Line intensity mapping (LIM) proposes to efficiently observe distant faint galaxies and map the matter density field at high redshift. Building upon the formalism in a companion paper, we first highlight the degeneracies between cosmology and astrophysics in LIM. We discuss what can be constrained from measurements of the mean intensity and redshift-space power spectra. With a sufficient spectral resolution, the large-scale redshift-space distortions of the 2-halo term can be measured, helping to break the degeneracy between bias and mean intensity. With a higher spectral resolution, measuring the small-scale redshift-space distortions disentangles the 1-halo and shot noise terms. Cross-correlations with external galaxy catalogs or lensing surveys further break degeneracies. We derive requirements for experiments similar to SPHEREx, HETDEX, CDIM, COMAP and CONCERTO. We then revisit the question of the optimality of the LIM observables, compared to galaxy detection, for astrophysics and cosmology. We use a matched filter to compute the luminosity detection threshold for individual sources. We show that LIM contains information about galaxies too faint to detect, in the high-noise or high-confusion regimes. We quantify the sparsity and clustering bias of the detected sources and compare them to LIM, showing in which cases LIM is a better tracer of the matter density. We extend previous work by answering these questions as a function of Fourier scale, including for the first time the effect of cosmic variance, pixel-to-pixel correlations, luminosity-dependent clustering bias and redshift-space distortions.
Long Live The Image: Container-Native Data Persistence in Production

Containerization plays a crucial role in the de facto technology stack for implementing microservices architecture (each microservice has its own database in most cases). Nevertheless, there are still fierce debates on containerizing production databases, mainly due to the data persistence issues and concerns. Driven by a project of refactoring an Automated Machine Learning system, this research proposes the container-native data persistence as a conditional solution to running database containers in production. In essence, the proposed solution distinguishes the stateless data access (i.e. reading) from the stateful data processing (i.e. creating, updating, and deleting) in databases. A master database handles the stateful data processing and dumps database copies for building container images, while the database containers will keep stateless at runtime, based on the preloaded dump in the image. Although there are delays in the state/image update propagation, this solution is particularly suitable for the read-only, the eventual consistency, and the asynchronous processing scenarios. Moreover, with optimal tuning (e.g., disabling locking), the portability and performance gains of a read-only database container would outweigh the performance loss in accessing data across the underlying image layers.
Exploring Privacy Implications in OAuth Deployments

Single sign-on authentication systems such as OAuth 2.0 are widely used in web services. They allow users to use accounts registered with major identity providers such as Google and Facebook to login on multiple services (relying parties). These services can both identify users and access a subset of the user's data stored with the provider. We empirically investigate the end-user privacy implications of OAuth 2.0 implementations in relying parties most visited around the world. We collect data on the use of OAuth-based logins in the Alexa Top 500 sites per country for five countries. We categorize user data made available by four identity providers (Google, Facebook, Apple and LinkedIn) and evaluate popular services accessing user data from the SSO platforms of these providers. Many services allow users to choose from multiple login options (with different identity providers). Our results reveal that services request different categories and amounts of personal data from different providers, with at least one choice undeniably more privacy-intrusive. These privacy choices (and their privacy implications) are highly invisible to users. Based on our analysis, we also identify areas which could improve user privacy and help users make informed decisions.