bluuebunny/crossref_metadata_2025 huggingface dataset:
Real-Time Graph Building on FPGAs for Machine Learning Trigger Applications in Particle Physics
Authors: Neu Marc , Becker Jürgen , Dorwarth Philipp , Ferber Torben , Reuter Lea , Stefkova Slavomira , Unger Kai
Published: March 2024

We present a design methodology that enables the semi-automatic generation of a hardware-accelerated graph building architectures for locally constrained graphs based on formally described detector definitions. In addition, we define a similarity measure in order to compare our locally constrained graph building approaches with commonly used k-nearest neighbour building approaches. To demonstrate the feasibility of our solution for particle physics applications, we implemented a real-time graph building approach in a case study for the Belle II central drift chamber using Field-Programmable Gate Arrays (FPGAs). Our presented solution adheres to all throughput and latency constraints currently present in the hardware-based trigger of the Belle II experiment. We achieve constant time complexity at the expense of linear space complexity and thus prove that our automated methodology generates online graph building designs suitable for a wide range of particle physics applications. By enabling an hardware-accelerated preprocessing of graphs, we enable the deployment of novel Graph Neural Networks (GNNs) in first-level triggers of particle physics experiments.
Towards misinformation mitigation on social media: novel user activity representation for modeling societal acceptance
Authors: Abouzeid Ahmed , Granmo Ole-Christoffer , Goodwin Morten , Webersik Christian
Published: March 2024

Intervention-based mitigation methods have become a common way to fight misinformation on Social Media (SM). However, these methods depend on how information spreads are modeled in a diffusion model. Unfortunately, there are no realistic diffusion models or enough diverse datasets to train diffusion prediction functions. In particular, there is an urgent need for mitigation methods and labeled datasets that capture the mutual temporal incidences of societal bias and societal engagement that drive the spread of misinformation. To that end, this paper proposes a novel representation of users’ activity on SM. We further embed these in a knapsack-based mitigation optimization approach. The optimization task is to find ways to mitigate political manipulation by incentivizing users to propagate factual information. We have created PEGYPT, a novel Twitter dataset to train a novel multiplex diffusion model with political bias, societal engagement, and propaganda events. Our approach aligns with recent theoretical findings on the importance of societal acceptance of information spread on SM as proposed by Olan et al. (Inf Syst Front 1–16, 2022). Our empirical results show significant differences from traditional representations, where the latter assume users’ exposure to misinformation can be mitigated despite their political bias and societal acceptance. Hence, our work opens venues for more realistic misinformation mitigation.
Prevalence, Inequalities, and Impact of Bullying in Adolescence: Insights from the #BeeWell Study
Authors: Thornton Emma , Panayiotou Margarita , Humphrey Neil
Published: March 2024

Measurement is fundamental to understanding and preventing bullying, but approaches in the field are inconsistent, producing much conflicting evidence. We illustrate this by demonstrating the sensitivity of findings to researcher-led analytical decisions (exposure threshold and type(s) of bullying considered) in a study addressing the following aims: (i) to determine the prevalence of bullying; (ii) to establish the nature and extent of inequalities in bullying exposure between different socio-demographic groups; (iii) to examine the relationship between bullying exposure and internalising symptoms; and (iv) to establish if this relationship varies between socio-demographic groups. Adolescents aged 12–15 (N = 35,825) attending 147 secondary schools in the #BeeWell study completed measures of bullying and internalising mental health difficulties. These data were linked to information on their socio-demographic characteristics (e.g. socio-economic disadvantage). A series of pre-registered analyses were undertaken. With regard to the first aim, the prevalence of bullying victimisation was found to range between 5 and 16%. In relation to the second aim, disparities in exposure to bullying were consistently found among gender and sexual minorities (vs cisgender heterosexual boys), those with special educational needs (vs those without special educational needs), younger students (vs older students), and those from more disadvantaged neighbourhoods (vs those from less disadvantaged neighbourhoods), irrespective of the bullying exposure threshold or type being considered. However, disparities among cisgender heterosexual girls (vs cisgender heterosexual boys) and ethnic minority groups (vs White students) varied by exposure threshold and type of bullying. Pertaining to the third aim, the population attributable fraction for the association between bullying exposure and internalising symptoms was found to range between 6 and 19%, with the odds ratio ranging between 3.55 and 4.20. Finally, in terms of the fourth aim, there was limited evidence that the magnitude of the impact of bullying victimisation varied across socio-demographic subgroups, except that bullying exposure was more strongly associated with internalising symptoms among LGBTQ+ young people and cisgender heterosexual girls (vs cisgender heterosexual boys), and less strongly associated with internalising symptoms among Black students (vs White students). Our findings speak to the importance of developing more consistent measurement practices in bullying research, with consequent implications for prevention and intervention. These implications are contextualised by consideration of study strengths and limitations.
Low-level memory and timing analysis of flight code for unmanned aerial systems
Authors: Saleab Micheal , Sax Franz , Schumann Johann , Holzapfel Florian
Published: March 2024

The development of flight software for Unmanned Aerial Systems (UAS) is challenging due to the absence of an established development process defined by aerospace certification authorities. This research paper outlines our methods and tools for analyzing flight-critical UAS control software on the target hardware. We present our toolchain and methodology for evaluating the flight control computer stack, runtime memory, and timing characteristics. Additionally, we compare the performance of the flight control computer under various hardware and cache settings to justify, which hardware features should be enabled. The tools and processes employed in this research are deployable to any other development environment and are not restricted to the specific target hardware used in this paper.
Preparation of some selective glass–ceramics from nano-silica within the Li2O–SiO2 system with ZrO2 for future dental applications
Authors: ElBatal F. H. , Marzouk M. A. , Azooz M. A. , Elbatal H. A.
Published: March 2024

Many recent studies have indicated that some modified silicate glass–ceramics are considered and recommended to be part of the process of dental applications. Examples from the recommended glass–ceramics include modified lithium silicate with various dopants (ZrO2, CeO2), mica-based glass–ceramics, and leucite-based glass–ceramics. The present study employs a new direction of research in the preparation of modified lithium silicate glasses containing varying dopant percents of ZrO2 to produce the parent glasses using nano-silica as an essential chemical component in comparison with silica. The ZrO2-doped glass–ceramic reveals the crystalline phase of lithium aluminosilicate (Li5AlSi2O8) due to the effect of ZrO2. The modified lithium silicate glasses doped with ZrO2 prepared from nano silica indicate their high mechanical properties and can be primarily recommended for dental applications.
Encapsulating Epigallocatechin-3-Gallate (EGCG) in Chitosan Nanoparticles Influenced Multiple Genes Controlling Oncostatic Signaling Pathways in HepG2 Cells
Authors: Shabana Sameh M. , Neamatallah Mustafa , Said Muhamad M. A. , Othman Azza I. , Ammar Omar A. , Amer Maher A. , El-Missiry Mohamed A.
Published: March 2024

The primary polyphenol in green tea, epigallocatechin-3-gallate (EGCG), is the primary active polyphenol in green tea that showed a remarkable anticancer effect in a variety of cancer types including liver cancer. However, its anticancer impact on gene expressions related to liver cancer proliferation and apoptosis is limited. The current study investigated the oncostatic influence of chitosan encapsulating EGCG (Chit-nanoEGCG) on human hepatocellular carcinoma HepG2 cells compared with its native form and the conventional anticancer drug cisplatin in vitro. The Chit-nanoEGCG caused a dose-dependent decrease in cell viability and significantly induced apoptosis compared with control. Flow cytometric analysis confirmed the results of RT-qPCR, displaying a significant increase in the expression of transcriptomes (P53, Bax, Caspase-3, Caspase-9, and PARP) with a significant decrease in the antiapoptotic Bcl-2 gene. Also, there was a significant decrease in transcription genes (OCT4 and SOX2) and receptor genes (CD133, NOTCH1, c-MET, and Ezrin) but an increase in CD95 expression. Furthermore, there was a highly significant decrease in oncogenes (mTOR, PI3K, RALA, and BMI) in HepG2 cells after Chit-nanoEGCG treatment when compared with the control group. The current findings indicate that Chit-nanoEGCG had a significant impact on a number of genes involved in controlling signaling pathways to inhibit the proliferation and development of HepG2 cells. In addition, encapsulating EGCG in chitosan nanoparticles increases its antitumor effectiveness compared to its native form, which encourages the use of various polyphenols in nanochemotherapy for cancer treatment. The finding that the nanoparticles (NPs) influenced the expression of genes involved in apoptosis and proliferation enables the development of medical chemotherapeutic agent for the treatment of hepatocellular carcinoma.

Graphical Abstract
Poststroke Care Pathways and Spasticity Treatment: A Retrospective Study in Alberta
Authors: Satkunam Lalith , Dukelow Sean P. , Yu Jaime , McNeil Stephen , Luu Huong , Martins Karen J.B. , Vu Khanh , Nguyen Phuong Uyen , Richer Lawrence , Williamson Tyler , Klarenbach Scott W.
Published: March 2024

Background:

Limited evidence exists regarding care pathways for stroke survivors who do and do not receive poststroke spasticity (PSS) treatment.

Methods:

Administrative data was used to identify adults who experienced a stroke and sought acute care between 2012 and 2017 in Alberta, Canada. Pathways of stroke care within the health care system were determined among those who initiated PSS treatment (PSS treatment group: outpatient pharmacy dispensation of an anti-spastic medication, focal chemo-denervation injection, or a spasticity tertiary clinic visit) and those who did not (non-PSS treatment group). Time from the stroke event until spasticity treatment initiation, and setting where treatment was initiated were reported. Descriptive statistics were performed.

Results:

Health care settings within the pathways of stroke care that the PSS (n = 1,079) and non-PSS (n = 22,922) treatment groups encountered were the emergency department (86 and 84%), acute inpatient care (80 and 69%), inpatient rehabilitation (40 and 12%), and long-term care (19 and 13%), respectively. PSS treatment was initiated a median of 291 (interquartile range 625) days after the stroke event, and most often in the community when patients were residing at home (45%), followed by “other” settings (22%), inpatient rehabilitation (18%), long-term care (11%), and acute inpatient care (4%).

Conclusions:

To our knowledge, this is the first population based cohort study describing pathways of care among adults with stroke who subsequently did or did not initiate spasticity treatment. Areas for improvement in care may include strategies for earlier identification and treatment of PSS.
State-society relations and government technology: a survey of public awareness and communication in Hong Kong
Authors: Hartley Kris
Published: March 2024

A survey of Hong Kong residents finds that public support for government technology, as understood through the concept of smart cities, is associated with concept-awareness and official communications. The statistical analysis identifies moderating effects attributable to personal social media use and controls for personal ideological views about scope of government intervention and perceived political legitimacy of smart city policies. The study builds on a growing body of empirical scholarship about public support for government technology, while also addressing a practical trend in urban governance: the growing sophistication of technologies like artificial intelligence and their use in strengthening government capacities. The Hong Kong case exemplifies ambitious investments in technology by governments and, at the time of the survey, relatively high freedom of political expression. The study’s findings help refine theories about state-society relations in the rapidly evolving context of technology for public sector use.
The challenge of youth unemployment in Nigeria
Authors: Virk Amrit , Nelson Ediomo-Ubong , Dele-Adedeji Ini
Published: March 2024

Nigeria is home to a significant and growing “youth” population, over a third of it below 24 years of age. The demographic potential for productivity and growth this group represents occurs alongside large-scale unemployment among young people of working age. The “unemployment crisis” has deep historical roots and exists within a wider context of poor governance, insecurity, conflict, and poverty. Policy norms and practices to address youth unemployment in Nigeria largely centre on skill development and job creation, with complementary schemes selectively targeted to specific groups of vulnerable and poor individuals. Measures are typically ad hoc, detached from a coherent programme of sustainable reform. Pre-existing structural factors and capacity constraints also shape the effectiveness of these programmes. While a productivist focus within current policy is potentially empowering in giving young Nigerians “worker” status, it also detracts from attending to deep-rooted structural problems seen to affect young people in disproportionate ways. Securing meaningful choices and lives for Nigerian youth requires reframing youth unemployment beyond labour markets alone, and embedded in ideas of equality and collective action.
Lagrangian approach to nonlinear waves in non-dispersive and dispersive rotating shallow water magnetohydrodynamics
Authors: Zeitlin Vladimir
Published: March 2024

A Lagrangian approach to both hydrostatic non-dispersive in the short-wave range and non-hydrostatic dispersive rotating shallow-water magnetohydrodynamics is developed, and used to analyse weakly and fully nonlinear waves described by the model. Hyperbolic structure in the non-dispersive case is displayed and Riemann invariants are constructed. Characteristic equations are used to establish criteria of breaking and formation of shocks by magneto-gravity waves, and conditions of the appearance of contact discontinuities in Alfvén waves. As in the case of non-magnetic rotating shallow water, rotation cannot prevent breaking. The Lagrangian equations of the model are reduced to a single partial differential ‘master’ equation, which is used to analyse the propagation of weakly nonlinear waves of both families, with or without weak rotation, and with or without weak short-wave dispersion. Corresponding modulation equations are constructed and their main properties sketched. The same master equation is used to obtain fully nonlinear finite-amplitude wave solutions in particular cases of no short-wave dispersion or no rotation.
Triangular matrix categories over quasi-hereditary categories
Authors: Ochoa De La Cruz Rafael Francisco , Ortíz Morales Martin , Santiago Vargas Valente
Published: March 2024

In this paper, we prove that the lower triangular matrix category
$\Lambda =\left [ \begin{smallmatrix} \mathcal{T}&0\\ M&\mathcal{U} \end{smallmatrix} \right ]$
, where
$\mathcal{T}$
and
$\mathcal{U}$
are
$\textrm{Hom}$
-finite, Krull–Schmidt
$K$
-quasi-hereditary categories and
$M$
is an
$\mathcal{U}\otimes _K \mathcal{T}^{op}$
-module that satisfies suitable conditions, is quasi-hereditary. This result generalizes the work of B. Zhu in his study on triangular matrix algebras over quasi-hereditary algebras. Moreover, we obtain a characterization of the category of the
$_\Lambda \Delta$
-filtered
$\Lambda$
-modules.
With or without the European Union: the convention for the protection of the Black Sea against pollution
Authors: Bayramoglu Basak , Haita-Falah Corina
Published: March 2024

The Black Sea is an enclosed sea surrounded by six coastal countries, of which Bulgaria and Romania are EU Member States. The Convention for the Protection of the Black Sea Against Pollution was ratified in 1994 by all coastal countries. This Convention is the only European regional sea convention to which the EU is not a Party. While Romania and Bulgaria are in favor of EU accession to the Convention, Turkey, Russia and Ukraine thus far have blocked accession. In this paper, we develop a negotiation model with endogenous enforcement and exogenous fraud to analyze the different positions of groups of coastal countries relative to EU accession to the Convention. Our model contributes to defining a proposal that the EU could make to the opposing states such that they accept the EU as a Party to the Convention. In that context we investigate also whether Romania and Bulgaria might be better off delegating their decision power to the EU, rather than retaining their individual voting rights.
Human Genetics Society of Australasia Position Statement: Predictive and Presymptomatic Genetic Testing in Adults and Children
Authors: Vears Danya F. , McLean Alison , La Spina Chloe , McInerney-Leo Aideen
Published: March 2024

This Position Statement provides guidelines for health professionals who work with individuals and families seeking predictive genetic testing and laboratory staff conducting the tests. It presents the major practical, psychosocial and ethical considerations associated with presymptomatic and predictive genetic testing in adults who have the capacity to make a decision, children and young people who lack capacity, and adults living with reduced or fluctuating cognitive capacity.

Predictive Testing Recommendations: (1) Predictive testing in adults, young people and children should only be offered with pretest genetic counseling, and the option of post-test genetic counseling. (2) An individual considering whether to have a predictive test should be supported to make an autonomous and informed decision. Regarding Children and Young People: (1) Predictive testing should only be offered to children and young people for conditions where there is likely to be a direct medical benefit to them through surveillance, use of prevention strategies, or other medical interventions in the immediate future. (2) Where symptoms are likely to develop in childhood, in the absence of direct medical benefit from this knowledge, genetic health professionals and parents/guardians should discuss whether undertaking predictive testing is the best course of action for the child and the family as a whole. (3) Where symptoms are likely to develop in adulthood, the default position should be to postpone predictive testing until the young person achieves the capacity to make an autonomous and informed decision. This is applicable regardless of whether there is some action that can be taken in adulthood.
Observations of Energy Conversion Caused by Magnetic Reconnection at a Dipolarization Front
Authors: Jiang K. , Huang S. Y. , Yuan Z. G. , Xiong Q. Y. , Xu S. B. , Lin R. T.
Published: March 2024

Dipolarization fronts (DFs) are widely believed to host energy conversion processes. However, which mechanism is responsible for the energy conversion is still obscure. Using data from the Magnetospheric Multiscale mission, a current sheet is observed at a DF. This current sheet is caused by interchange instability bending the edge of the DF. Inside the current sheet, Hall electromagnetic field, super Alfvénic electron jets, demagnetization of ions and electrons, strong energy conversion, and steady ion flow and temperature are observed, indicating an electron‐only reconnection at the DF. The duskward plasma flow, which may be deflected by the DF, compresses the bent edges of the DF. As a result, the width of the current sheet between two adjacent bent edges of the DF reduces, and then reconnection begins. Our observations give direct evidence that magnetic reconnection results in energy conversion at a DF.
Effects of Pressure and Temperature Changes on Shock Remanence Acquisition for Single‐Domain Titanomagnetite‐Bearing Basalt
Authors: Sato Masahiko , Kurosawa Kosuke , Hasegawa Sunao , Takahashi Futoshi
Published: March 2024

Knowledge of the shock remanent magnetization (SRM) property is crucial for interpreting the spatial change in a magnetic anomaly observed over an impact crater. This study conducted two series of impact‐induced SRM acquisition experiments by varying the applied field intensity (0–400 μT) and impact conditions. Systematic remanence measurements of cube‐shaped subsamples cut from shocked basalt containing single‐domain titanomagnetite were conducted to investigate the effects of changes in pressure and temperature on the SRM acquisition. The peak pressure and temperature distributions in the shocked samples were estimated using shock‐physics modeling. SRM intensity was proportional to the applied field intensity of up to 400 μT. SRM intensity data for peak pressure and temperature of up to 8.0 GPa and 530 K, respectively, clearly show that it increases with increasing pressure and decreases with increasing temperature. The SRM has unblocking temperature components up to a Curie temperature of 510 K, and it easily demagnetizes with alternating field demagnetization. The observed SRM properties can be explained by the pressure‐induced microcoercivity reduction and temperature‐induced modification of the blocking curve. Although the remanence acquisition efficiency of the SRM is significantly lower than that of the thermoremanent magnetization (TRM), the magnetic anomaly originating from the SRM distribution in a broader region may show a contribution comparable to that of the impact‐induced TRM distribution in a narrow region.
Quantifying Uncertainty in Sustainable Biomass and Production of Biotic Carbon in Enceladus' Notional Methanogenic Biosphere
Authors: Higgins Peter M. , Chen Weibin , Glein Christopher R. , Cockell Charles S. , Sherwood Lollar Barbara
Published: March 2024

Beneath Enceladus' ice crust lies an ocean which might host habitable conditions. Here, the scale and productivity of a notional Enceladean methanogenic biosphere are computed as a function of the core‐to‐ocean flux of hydrogen and the ratio between abiotic and biotic methane in Enceladus' space plume. Habitats with an ocean‐top pH range of 8–9 have up to 40%–60% probability of being energy‐limited. Those at pH > 9 are increasingly uninhabitable, and those <8.5 are increasingly likely to host exponential growth, possibly leading to compositional inconsistencies between the ocean and Cassini gas observations. In those cases, energy‐based habitability models cannot infer an inhabited Enceladus consistent with both Earth life and Cassini measurements without including additional microbial growth limiters such as nutrient limitation, toxicity, or spatial constraints. If methanogens are isolated to a 350 K seafloor habitat and consume 10 mol s−1 of H2, the most probable biomass is 103, 103.7 kg C with ocean‐top pH 8,9, respectively. Biomass production consistent with space plume fluxes is 104–106 kgC yr−1—milligrams of cellular carbon per kilogram of H2O ejected—but requires that >50% of the space plume methane is biotic. Alternative scenarios are presented, and biomass is generally lower when habitat temperature is higher. Ocean biomass density cannot yet be reliably estimated owing to uncertainties in the scale and physicochemical properties of Enceladus' putative habitats. Evaluating abiotic to biotic ratios in plume methane and organic material could help identify false negative results from life detection missions and constrain the scale of an underlying biosphere.
Near-zero stiffness accelerometer with buckling of tunable electrothermal microbeams
Authors: Hussein Hussein , Wang Chen , Amendoeira Esteves Rui , Kraft Michael , Fariborzi Hossein
Published: March 2024

Pre-shaped microbeams, curved or inclined, are widely used in MEMS for their interesting stiffness properties. These mechanisms allow a wide range of positive and negative stiffness tuning in their direction of motion. A mechanism of pre-shaped beams with opposite curvature, connected in a parallel configuration, can be electrothermally tuned to reach a near-zero or negative stiffness behavior at the as-fabricated position. The simple structure helps incorporate the tunable spring mechanism in different designs for accelerometers, even with different transduction technologies. The sensitivity of the accelerometer can be considerably increased or tuned for different applications by electrothermally changing the stiffness of the spring mechanism. Opposite inclined beams are implemented in a capacitive micromachined accelerometer. The measurements on fabricated prototypes showed more than 55 times gain in sensitivity compared to their initial sensitivity. The experiments showed promising results in enhancing the resolution of acceleration sensing and the potential to reach unprecedent performance in micromachined accelerometers.
Chemogenetic inhibition of central amygdala CRF-expressing neurons decreases alcohol intake but not trauma-related behaviors in a rat model of post-traumatic stress and alcohol use disorder
Authors: Cruz Bryan , Vozella Valentina , Borgonetti Vittoria , Bullard Ryan , Bianchi Paula C. , Kirson Dean , Bertotto Luisa B. , Bajo Michal , Vlkolinsky Roman , Messing Robert O. , Zorrilla Eric P. , Roberto Marisa
Published: March 2024

Post-traumatic stress disorder (PTSD) and alcohol use disorder (AUD) are often comorbid. Few treatments exist to reduce comorbid PTSD/AUD. Elucidating the mechanisms underlying their comorbidity could reveal new avenues for therapy. Here, we employed a model of comorbid PTSD/AUD, in which rats were subjected to a stressful shock in a familiar context followed by alcohol drinking. We then examined fear overgeneralization and irritability in these rats. Familiar context stress elevated drinking, increased fear overgeneralization, increased alcohol-related aggressive signs, and elevated peripheral stress hormones. We then examined transcripts of stress- and fear-relevant genes in the central amygdala (CeA), a locus that regulates stress-mediated alcohol drinking. Compared with unstressed rats, stressed rats exhibited increases in CeA transcripts for Crh and Fkbp5 and decreases in transcripts for Bdnf and Il18. Levels of Nr3c1 mRNA, which encodes the glucocorticoid receptor, increased in stressed males but decreased in stressed females. Transcripts of Il18 binding protein (Il18bp), Glp-1r, and genes associated with calcitonin gene-related peptide signaling (Calca, Ramp1, Crlr-1, and Iapp) were unaltered. Crh, but not Crhr1, mRNA was increased by stress; thus, we tested whether inhibiting CeA neurons that express corticotropin-releasing factor (CRF) suppress PTSD/AUD-like behaviors. We used Crh-Cre rats that had received a Cre-dependent vector encoding hM4D(Gi), an inhibitory Designer Receptors Exclusively Activated by Designer Drugs. Chemogenetic inhibition of CeA CRF neurons reduced alcohol intake but not fear overgeneralization or irritability-like behaviors. Our findings suggest that CeA CRF modulates PTSD/AUD comorbidity, and inhibiting CRF neural activity is primarily associated with reducing alcohol drinking but not trauma-related behaviors that are associated with PTSD/AUD.
Genetic contribution to microglial activation in schizophrenia
Authors: Koskuvi Marja , Pörsti Elina , Hewitt Tristen , Räsänen Noora , Wu Ying-Chieh , Trontti Kalevi , McQuade Amanda , Kalyanaraman Shringaa , Ojansuu Ilkka , Vaurio Olli , Cannon Tyrone D. , Lönnqvist Jouko , Therman Sebastian , Suvisaari Jaana , Kaprio Jaakko , Blurton-Jones Mathew , Hovatta Iiris , Lähteenvuo Markku , Rolova Taisia , Lehtonen Šárka , Tiihonen Jari , Koistinaho Jari
Published: March 2024

Several lines of evidence indicate the involvement of neuroinflammatory processes in the pathophysiology of schizophrenia (SCZ). Microglia are brain resident immune cells responding toward invading pathogens and injury-related products, and additionally, have a critical role in improving neurogenesis and synaptic functions. Aberrant activation of microglia in SCZ is one of the leading hypotheses for disease pathogenesis, but due to the lack of proper human cell models, the role of microglia in SCZ is not well studied. We used monozygotic twins discordant for SCZ and healthy individuals to generate human induced pluripotent stem cell-derived microglia to assess the transcriptional and functional differences in microglia between healthy controls, affected twins and unaffected twins. The microglia from affected twins had increased expression of several common inflammation-related genes compared to healthy individuals. Microglia from affected twins had also reduced response to interleukin 1 beta (IL1β) treatment, but no significant differences in migration or phagocytotic activity. Ingenuity Pathway Analysis (IPA) showed abnormalities related to extracellular matrix signaling. RNA sequencing predicted downregulation of extracellular matrix structure constituent Gene Ontology (GO) terms and hepatic fibrosis pathway activation that were shared by microglia of both affected and unaffected twins, but the upregulation of major histocompatibility complex (MHC) class II receptors was observed only in affected twin microglia. Also, the microglia of affected twins had heterogeneous response to clozapine, minocycline, and sulforaphane treatments. Overall, despite the increased expression of inflammatory genes, we observed no clear functional signs of hyperactivation in microglia from patients with SCZ. We conclude that microglia of the patients with SCZ have gene expression aberrations related to inflammation response and extracellular matrix without contributing to increased microglial activation.
High intensity functional training for people with spinal cord injury & their care partners
Authors: Handlery Reed , Handlery Kaci , Kahl Dana , Koon Lyndsie , Regan Elizabeth W.
Published: March 2024

Study design

Non-randomized clinical trial.

Objectives

Examine the feasibility, physical and psychosocial effects of a high intensity functional training (HIFT) exercise program for people with spinal cord injury (pSCI) and their care partners (CPs).

Setting

Community fitness center in a Medically Underserved Area (Fort Smith, USA.)

Methods

A single-group design with three assessment points (before the program, at midpoint (13 weeks), and post-program (25 weeks) was used to examine the effects of up to 49 HIFT sessions over 25-weeks. Sessions were 60 to 75 min in duration and adapted to the abilities of participants. Feasibility measures included recruitment, retention, attendance, safety and fidelity (exercise intensity rated via session-Rating of Perceived Exertion (RPE). Physical measures included cardiovascular endurance, anaerobic power, and muscular strength. Psychosocial measures included perceived social support for exercise, exercise self-efficacy and health-related quality of life.

Results

Fourteen pSCI (7 with paraplegia and 7 with tetraplegia, 2 females) and 6 CPs (4 females) were included (median age = 60) (IQR = 15.8). Recruitment rates were 40% for pSCI and 32% for CPs. On average, participants attended 73% (22%) of exercise sessions with a median session-RPE of 5 (IQR = 1). Retention rates were 83% and 67% for pSCI and CPs, respectively. For pSCI and their CPs, large effect sizes were observed for cardiovascular endurance, anaerobic power, muscular strength, and social support for exercise.

Conclusions

For pSCI and their CPs, HIFT appears feasible and potentially leads to improvements in physical and psychosocial health for both groups.
Towards a scalable approach to assess speech organization across the psychosis-spectrum -online assessment in conjunction with automated transcription and extraction of speech measures
Authors: Olah Julianna , Cummins Nicholas , Arribas Maite , Gibbs-Dean Toni , Molina Elena , Sethi Divina , Kempton Matthew J. , Morgan Sarah , Spencer Tom , Diederen Kelly
Published: March 2024

Automatically extracted measures of speech constitute a promising marker of psychosis as disorganized speech is associated with psychotic symptoms and predictive of psychosis-onset. The potential of speech markers is, however, hampered by (i) lengthy assessments in laboratory settings and (ii) manual transcriptions. We investigated whether a short, scalable data collection (online) and processing (automated transcription) procedure would provide data of sufficient quality to extract previously validated speech measures. To evaluate the fit of our approach for purpose, we assessed speech in relation to psychotic-like experiences in the general population. Participants completed an 8-minute-long speech task online. Sample 1 included measures of psychometric schizotypy and delusional ideation (N = 446). Sample 2 included a low and high psychometric schizotypy group (N = 144). Recordings were transcribed both automatically and manually, and connectivity, semantic, and syntactic speech measures were extracted for both types of transcripts. 73%/86% participants in sample 1/2 completed the experiment. Nineteen out of 25 speech measures were strongly (r > 0.7) and significantly correlated between automated and manual transcripts in both samples. Amongst the 14 connectivity measures, 11 showed a significant relationship with delusional ideation. For the semantic and syntactic measures, On Topic score and the Frequency of personal pronouns were negatively correlated with both schizotypy and delusional ideation. Combined with demographic information, the speech markers could explain 11–14% of the variation of delusional ideation and schizotypy in Sample 1 and could discriminate between high-low schizotypy with high accuracy (0.72−0.70, AUC = 0.78–0.79) in Sample 2. The moderate to high retention rate, strong correlation of speech measures across manual and automated transcripts and sensitivity to psychotic-like experiences provides initial evidence that online collected speech in combination with automatic transcription is a feasible approach to increase accessibility and scalability of speech-based assessment of psychosis.
Identification of FasL as a crucial host factor driving COVID-19 pathology and lethality
Authors: Albert Marie-Christine , Uranga-Murillo Iratxe , Arias Maykel , De Miguel Diego , Peña Natacha , Montinaro Antonella , Varanda Ana Beatriz , Theobald Sebastian J. , Areso Itziar , Saggau Julia , Koch Manuel , Liccardi Gianmaria , Peltzer Nieves , Rybniker Jan , Hurtado-Guerrero Ramón , Merino Pedro , Monzón Marta , Badiola Juan J. , Reindl-Schwaighofer Roman , Sanz-Pamplona Rebeca , Cebollada-Solanas Alberto , Megyesfalvi Zsolt , Dome Balazs , Secrier Maria , Hartmann Boris , Bergmann Michael , Pardo Julián , Walczak Henning
Published: March 2024

The dysregulated immune response and inflammation resulting in severe COVID-19 are still incompletely understood. Having recently determined that aberrant death-ligand-induced cell death can cause lethal inflammation, we hypothesized that this process might also cause or contribute to inflammatory disease and lung failure following SARS-CoV-2 infection. To test this hypothesis, we developed a novel mouse-adapted SARS-CoV-2 model (MA20) that recapitulates key pathological features of COVID-19. Concomitantly with occurrence of cell death and inflammation, FasL expression was significantly increased on inflammatory monocytic macrophages and NK cells in the lungs of MA20-infected mice. Importantly, therapeutic FasL inhibition markedly increased survival of both, young and old MA20-infected mice coincident with substantially reduced cell death and inflammation in their lungs. Intriguingly, FasL was also increased in the bronchoalveolar lavage fluid of critically-ill COVID-19 patients. Together, these results identify FasL as a crucial host factor driving the immuno-pathology that underlies COVID-19 severity and lethality, and imply that patients with severe COVID-19 may significantly benefit from therapeutic inhibition of FasL.
Promastigote EPS secretion and haptomonad biofilm formation as evolutionary adaptations of trypanosomatid parasites for colonizing honeybee hosts
Authors: Carreira de Paula Jéssica , García Olmedo Pedro , Gómez-Moracho Tamara , Buendía-Abad María , Higes Mariano , Martín-Hernández Raquel , Osuna Antonio , de Pablos Luis Miguel
Published: March 2024

Bees are major pollinators involved in the maintenance of all terrestrial ecosystems. Biotic and abiotic factors placing these insects at risk is a research priority for ecological and agricultural sustainability. Parasites are one of the key players of this global decline and the study of their mechanisms of action is essential to control honeybee colony losses. Trypanosomatid parasites and particularly the Lotmaria passim are widely spread in honeybees, however their lifestyle is poorly understood. In this work, we show how these parasites are able to differentiate into a new parasitic lifestyle: the trypanosomatid biofilms. Using different microscopic techniques, we demonstrated that the secretion of Extracellular Polymeric Substances by free-swimming unicellular promastigote forms is a prerequisite for the generation and adherence of multicellular biofilms to solid surfaces in vitro and in vivo. Moreover, compared to human-infective trypanosomatid parasites our study shows how trypanosomatid parasites of honeybees increases their resistance and thus resilience to drastic changes in environmental conditions such as ultralow temperatures and hypoosmotic shock, which would explain their success thriving within or outside their hosts. These results set up the basis for the understanding of the success of this group of parasites in nature and to unveil the impact of such pathogens in honeybees, a keystones species in most terrestrial ecosystems.
MLMD: a programming-free AI platform to predict and design materials
Authors: Ma Jiaxuan , Cao Bin , Dong Shuya , Tian Yuan , Wang Menghuan , Xiong Jie , Sun Sheng
Published: March 2024

Accelerating the discovery of advanced materials is crucial for modern industries, aerospace, biomedicine, and energy. Nevertheless, only a small fraction of materials are currently under experimental investigation within the vast chemical space. Materials scientists are plagued by time-consuming and labor-intensive experiments due to lacking efficient material discovery strategies. Artificial intelligence (AI) has emerged as a promising instrument to bridge this gap. Although numerous AI toolkits or platforms for material science have been developed, they suffer from many shortcomings. These include primarily focusing on material property prediction and being unfriendly to material scientists lacking programming experience, especially performing poorly with limited data. Here, we developed MLMD, an AI platform for materials design. It is capable of effectively discovering novel materials with high-potential advanced properties end-to-end, utilizing model inference, surrogate optimization, and even working in situations of data scarcity based on active learning. Additionally, it integrates data analysis, descriptor refactoring, hyper-parameters auto-optimizing, and properties prediction. It also provides a web-based friendly interface without need programming and can be used anywhere, anytime. MLMD is dedicated to the integration of material experiment/computation and design, and accelerate the new material discovery with desired one or multiple properties. It demonstrates the strong power to direct experiments on various materials (perovskites, steel, high-entropy alloy, etc). MLMD will be an essential tool for materials scientists and facilitate the advancement of materials informatics.
Genomic analysis of 116 autism families strengthens known risk genes and highlights promising candidates
Authors: Viggiano Marta , Ceroni Fabiola , Visconti Paola , Posar Annio , Scaduto Maria Cristina , Sandoni Laura , Baravelli Irene , Cameli Cinzia , Rochat Magali J. , Maresca Alessandra , Vaisfeld Alessandro , Gentilini Davide , Calzari Luciano , Carelli Valerio , Zody Michael C. , Maestrini Elena , Bacchelli Elena
Published: March 2024

Autism spectrum disorder (ASD) is a complex neurodevelopmental condition with a strong genetic component in which rare variants contribute significantly to risk. We performed whole genome and/or exome sequencing (WGS and WES) and SNP-array analysis to identify both rare sequence and copy number variants (SNVs and CNVs) in 435 individuals from 116 ASD families. We identified 37 rare potentially damaging de novo SNVs (pdSNVs) in the cases (n = 144). Interestingly, two of them (one stop-gain and one missense variant) occurred in the same gene, BRSK2. Moreover, the identification of 8 severe de novo pdSNVs in genes not previously implicated in ASD (AGPAT3, IRX5, MGAT5B, RAB8B, RAP1A, RASAL2, SLC9A1, YME1L1) highlighted promising candidates. Potentially damaging CNVs (pdCNVs) provided support to the involvement of inherited variants in PHF3, NEGR1, TIAM1 and HOMER1 in neurodevelopmental disorders (NDD), although mostly acting as susceptibility factors with incomplete penetrance. Interpretation of identified pdSNVs/pdCNVs according to the ACMG guidelines led to a molecular diagnosis in 19/144 cases, although this figure represents a lower limit and is expected to increase thanks to further clarification of the role of likely pathogenic variants in ASD/NDD candidate genes not yet established. In conclusion, our study highlights promising ASD candidate genes and contributes to characterize the allelic diversity, mode of inheritance and phenotypic impact of de novo and inherited risk variants in ASD/NDD genes.
The neural and cognitive basis of expository text comprehension
Authors: Keller Timothy A. , Mason Robert A. , Legg Aliza E. , Just Marcel Adam
Published: March 2024

As science and technology rapidly progress, it becomes increasingly important to understand how individuals comprehend expository technical texts that explain these advances. This study examined differences in individual readers’ technical comprehension performance and differences among texts, using functional brain imaging to measure regional brain activity while students read passages on technical topics and then took a comprehension test. Better comprehension of the technical passages was related to higher activation in regions of the left inferior frontal gyrus, left superior parietal lobe, bilateral dorsolateral prefrontal cortex, and bilateral hippocampus. These areas are associated with the construction of a mental model of the passage and with the integration of new and prior knowledge in memory. Poorer comprehension of the passages was related to greater activation of the ventromedial prefrontal cortex and the precuneus, areas involved in autobiographical and episodic memory retrieval. More comprehensible passages elicited more brain activation associated with establishing links among different types of information in the text and activation associated with establishing conceptual coherence within the text representation. These findings converge with previous behavioral research in their implications for teaching technical learners to become better comprehenders and for improving the structure of instructional texts, to facilitate scientific and technological comprehension.
Starfysh integrates spatial transcriptomic and histologic data to reveal heterogeneous tumor–immune hubs
Authors: He Siyu , Jin Yinuo , Nazaret Achille , Shi Lingting , Chen Xueer , Rampersaud Sham , Dhillon Bahawar S. , Valdez Izabella , Friend Lauren E. , Fan Joy Linyue , Park Cameron Y. , Mintz Rachel L. , Lao Yeh-Hsing , Carrera David , Fang Kaylee W. , Mehdi Kaleem , Rohde Madeline , McFaline-Figueroa José L. , Blei David , Leong Kam W. , Rudensky Alexander Y. , Plitas George , Azizi Elham
Published: March 2024

Spatially resolved gene expression profiling provides insight into tissue organization and cell–cell crosstalk; however, sequencing-based spatial transcriptomics (ST) lacks single-cell resolution. Current ST analysis methods require single-cell RNA sequencing data as a reference for rigorous interpretation of cell states, mostly do not use associated histology images and are not capable of inferring shared neighborhoods across multiple tissues. Here we present Starfysh, a computational toolbox using a deep generative model that incorporates archetypal analysis and any known cell type markers to characterize known or new tissue-specific cell states without a single-cell reference. Starfysh improves the characterization of spatial dynamics in complex tissues using histology images and enables the comparison of niches as spatial hubs across tissues. Integrative analysis of primary estrogen receptor (ER)-positive breast cancer, triple-negative breast cancer (TNBC) and metaplastic breast cancer (MBC) tissues led to the identification of spatial hubs with patient- and disease-specific cell type compositions and revealed metabolic reprogramming shaping immunosuppressive hubs in aggressive MBC.
Single-cell multi-ome regression models identify functional and disease-associated enhancers and enable chromatin potential analysis
Authors: Mitra Sneha , Malik Rohan , Wong Wilfred , Rahman Afsana , Hartemink Alexander J. , Pritykin Yuri , Dey Kushal K. , Leslie Christina S.
Published: March 2024

We present a gene-level regulatory model, single-cell ATAC + RNA linking (SCARlink), which predicts single-cell gene expression and links enhancers to target genes using multi-ome (scRNA-seq and scATAC–seq co-assay) sequencing data. The approach uses regularized Poisson regression on tile-level accessibility data to jointly model all regulatory effects at a gene locus, avoiding the limitations of pairwise gene–peak correlations and dependence on peak calling. SCARlink outperformed existing gene scoring methods for imputing gene expression from chromatin accessibility across high-coverage multi-ome datasets while giving comparable to improved performance on low-coverage datasets. Shapley value analysis on trained models identified cell-type-specific gene enhancers that are validated by promoter capture Hi-C and are 11× to 15× and 5× to 12× enriched in fine-mapped eQTLs and fine-mapped genome-wide association study (GWAS) variants, respectively. We further show that SCARlink-predicted and observed gene expression vectors provide a robust way to compute a chromatin potential vector field to enable developmental trajectory analysis.