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Interfacial water engineering for enhanced pure water electrolysis
Dynamics of two distinct memory interactions during water seeking in <i>Drosophila</i>
Forming and forgetting memories shape our self-awareness and help us face future challenges. Therefore, understanding how memories are formed and how different memories interact in the brain is important. Previous studies have shown that thirsty flies sense humidity through ionotropic receptors, which help them locate water sources. Here, we showed that thirsty flies can be trained to associate specific odors with humidity to form a humidity memory that lasts for 30 min after association. Humidity memory formation requires the Ir93a and Ir40a ionotropic receptors, which are essential for environmental humidity sensing. Water memory takes precedence, leading to the forgetting of humidity memory by activating a small subset of dopaminergic neurons called protocerebral anterior medial (PAM)-γ4, that project to the restricted region of the mushroom body (MB) γ lobes. Adult-stage-specific silencing of Dop2R dopaminergic receptors in MB γ neurons prolongs humidity memory for 3 h. Live-brain calcium imaging and dopamine sensor studies revealed significantly increased PAM-γ4 neural activity after odor/humidity association, suggesting its role in forgetting the humidity memory. Our results suggest that overlapping neural circuits are responsible for the acquisition of water memory and forgetting humidity memory in thirsty flies.
Auditing the fairness of the US COVID-19 forecast hub’s case prediction models
The US COVID-19 Forecast Hub, a repository of COVID-19 forecasts from over 50 independent research groups, is used by the Centers for Disease Control and Prevention (CDC) for their official COVID-19 communications. As such, the Forecast Hub is a critical centralized resource to promote transparent decision making. While the Forecast Hub has provided valuable predictions focused on accuracy, there is an opportunity to evaluate model performance across social determinants such as race and urbanization level that have been known to play a role in the COVID-19 pandemic. In this paper, we carry out a comprehensive fairness analysis of the Forecast Hub model predictions and we show statistically significant diverse predictive performance across social determinants, with minority racial and ethnic groups as well as less urbanized areas often associated with higher prediction errors. We hope this work will encourage COVID-19 modelers and the CDC to report fairness metrics together with accuracy, and to reflect on the potential harms of the models on specific social groups and contexts.
Appointed time tracking control for marine surface vessels using the novel integral barrier function
Exotic mechanical properties enabled by countersnapping instabilities
Mechanical snapping instabilities are leveraged by natural systems, metamaterials, and devices for rapid sensing, actuation, and shape changes, as well as to absorb impact. In all current forms of snapping, shapes deform in the same direction as the exerted forces, even though there is no physical law that dictates this. Here, we realize countersnapping mechanical structures that respond in the opposite way. In contrast to regular snapping, countersnapping manifests itself in a sudden shortening transition under increasing tension or a sudden increase in tensile force under increasing extension. We design these structures by combining basic flexible building blocks that leverage geometric nonlinearities. We demonstrate experimentally that countersnapping can be employed to obtain new exotic properties, such as unidirectional stick–slip motion, switchable stiffness that does not otherwise affect the state of the system, and passive resonance avoidance. Moreover, we demonstrate that combining multiple countersnapping elements allows sequential stiffness switching for elements coupled in parallel, or instantaneous collective switching for elements in series. By expanding the repertoire of realizable elastic instabilities, our work opens routes to principles for mechanical sensing, computation, and actuation.
Understanding the impact of developmental coordination disorder on Belgian children and families: A national survey study
Background Developmental Coordination Disorder (DCD) is an under-recognized and often trivialized neurodevelopmental condition impacting five to six percent of children. This study aimed to map the impact of DCD on children and their families in Belgium. Methods The Australian ‘Impact for DCD’ questionnaire was translated and adapted to suit the Belgian context. Parents of 4-to-18-year-old children living in Belgium with movement difficulties consistent with DCD were invited to complete the online survey covering diagnosis, activities, school, therapy, and social and emotional impact. Results A total of 491 children were included in the analyses. First concerns emerged primarily at home (61.4%) at age 3.3 ± 2.25y, with help sought at age 4.7 ± 2.57y. Formal diagnosis occurred at age 6.9 ± 2.36y, with DCD (76.5%) and/or dyspraxia (38.4%) the most frequently received terms. DCD was generally unknown, especially within school settings. Nearly one in four children (23.2%) repeated a year of school. Reduced sleep quality (50.6%), fatigue after school (76.0%), difficulties with toilet training (47.9%) and speech articulation (52.3%), as well as elevated emotional problems (52.7%) and peer-related issues (46.4%), were prevalent. Most children received therapy (89.2%) but 59.1% of parents did not feel adequately supported to assist their child. Moreover, 37.5% of parents regularly took time off work to facilitate their child’s therapy attendance, while 49.1% had reduced their working hours or were contemplating doing so (16.7%). Parents expressed concerns about their child's future and well-being, with a prominent plea for guidance on supporting their child and increased awareness. Parents reported important strengths in their children, including empathy, creativity, cognitive abilities, perseverance, and good social and/or language skills. Conclusions These results highlight the significant impact of DCD from parents’ perspectives. The next step is to explore ways to empower and support parents, raise awareness, and collaborate with policymakers to address these challenges.
Comprehensive analysis of 42 psilocybin-producing fungal strains reveals metabolite diversity and species-specific clusters
Semaphorin 6A phase separation sustains a histone lactylation–dependent lactate buildup in pathological angiogenesis
Ischemic retinal diseases are major causes of blindness worldwide and are characterized by pathological angiogenesis. Epigenetic alterations in response to metabolic shifts in endothelial cells (ECs) suffice to underlie excessive angiogenesis. Lactate accumulation and its subsequent histone lactylation in ECs contribute to vascular disorders. However, the regulatory mechanism of establishing and sustaining lactylation modification remains elusive. Here, we showed that lactate accumulation induced histone lactylations on H3K9 and H3K18 in neovascular ECs in the proliferative stage of oxygen-induced retinopathy. Joint CUT&Tag and scRNA-seq analyses identified Prmt5 as a target of H3K9la and H3K18la in isolated retinal ECs. EC-specific deletion of Prmt5 since the early stage of revascularization suppressed a positive feedback loop of lactate production and histone lactylation, thus inhibiting neovascular tuft formation. Mechanistically, the C-terminal intrinsically disorder region (IDR) of the transmembrane semaphorin 6A (SEMA6A) forms liquid–liquid phase separation condensates to recruit RHOA and P300, facilitating P300 phosphorylation and histone lactylation cycle. Deletion of endothelial Sema6A reduced H3K9la and H3K18la at the promoter of PRMT5 and diminished its expression. The induction of histone lactylation by SEMA6A-IDR and its pro-angiogenic effect were abrogated by deletion of Prmt5 . Our study illustrates a sustainable histone lactylation machinery driven by phase separation-dependent lactyltransferase activation in dysregulated vascularization.
Socioeconomic status and older adult’s experiences of weight loss: a qualitative secondary analysis
Objectives Unintentional weight loss in older adults is common, with 15–20% of those aged >65 having clinically significant weight loss, associated with increased mortality and morbidity. People with socioeconomic disadvantage are more likely to be overweight but also to become frailer in older age. We explore if socioeconomic status impacts upon patients’ experience of unplanned weight loss. Methods Qualitative secondary analysis of 23 semi-structured interviews with older adults from two prior studies i), those at risk of frailty ii) those with cancer. Reflexive thematic analysis was conducted, using the lens of the Nutrition Equity Framework, on anonymised transcripts with formation of themes and subthemes, with relationships between themes investigated. Results Mean age 73 years, range 65–87; 34% male, Index of Multiple Deprivation Quintiles IMD 1 (n=9), IMD 2 (n=4), IMD 3 (n=3), IMD 4 (n=6), IMD 5 (n=1). Three major themes were identified. 1. ‘Healthcare Systems’; interactions with either public health or individual healthcare systems influence patient experiences of weight loss. 2. ‘Personal Factors’; that influence a patient’s view of weight loss and the likelihood of weight loss prompting help-seeking behaviour 3. ‘Can I Change?’; patients’ perspectives of their ability to implement change. Factors in each of the themes were understood through motivating (reinforcing) and demotivating (balancing) factors. Conclusions This study demonstrates that there is structural and individual inequity in individual views, identification, and clinical management of weight loss. The consequences of this disproportionately affect the most deprived, further confounding the inequalities that already exist.
Machine learning modeling and multi objective optimization of artificial detrusor
Profile of John Hopfield and Geoffrey Hinton: 2024 Nobel laureates in Physics
The 2024 Nobel Prize in Physics recognizes breakthroughs contributing to the emergence of a new understanding of the computations that underlie human intelligence, with profound implications for artificially intelligent systems. John Hopfield and Geoffrey Hinton played seminal roles in these breakthroughs. I begin by characterizing the scientific context in which the new understanding of intelligence began to arise. I then consider Hopfield’s and Hinton’s ideas and their centrality in the sciences of natural and artificial intelligence, while mentioning others who made major contributions. I conclude with a brief consideration of the current state of the fields these ideas have influenced and of the importance of governmental and scientific organizations in the past and future of these sciences.
Molecular changes, histopathology, and ultrasonic vocalization acoustic profiles of systemically dehydrated rats
Systemic hydration is known to promote optimal functioning of bodily systems—including the vocal folds. The impact of systemic dehydration on the biology of the vocal folds and the downstream effects of dehydration on voice output are not well understood. An in vivo rat model of systemic dehydration was employed to investigate vocal fold gene expression, histological changes, and acoustic changes in vocalization. Ultrasonic vocalizations (USVs) were recorded every day for 5 days (baseline), in male and female Long-Evans rats (N = 36, ages: 3–4 months) using an anticipatory reward paradigm. Next, rats were dehydrated (N = 18) using a published water-restriction model for 5 days or euhydrated (N = 18) and provided ad libitum access to water for 5 days. USVs were recorded daily during the dehydration/euhydration period. The USV variables were averaged at baseline and following dehydration/euhydration for individual animals, and the difference between these time periods was used for statistical analysis. USV analysis included total USV count, complexity ratio, duration (s), frequency range (kHz), and maximum intensity (dB). At the end of dehydration/euhydration, animals were euthanized, and kidney and vocal fold tissue samples were dissected and processed for histology and gene expression analysis. Compared to euhydrated rats, dehydrated male and female rats had significantly up-regulated gene expression of kidney renin (male p = 0.047; female p = 0.018), indicating physiologic dehydration. There were no statistically significant differences in the USV acoustic profile or histopathology between the two groups. Differential expression (p < 0.05) of several genes related to extracellular matrix remodeling, inflammatory responses, and water ion transport in the vocal folds was present. Our results indicate that mild systemic dehydration impacts gene expression in the vocal fold mucosa; however, these gene expression changes are not evident in the acoustic profile of vocalizations.
Recognition of chlorophyll rings using YOLOv8
Development of DPP-4-resistant CXCL9-Fc and CXCL10-Fc chemokines for effective cancer immunotherapy
CXCR3 is a chemokine receptor for three ligands: CXCL9, CXCL10, and CXCL11. Accumulating evidence, including data presented here, suggests that the interaction between CXCL9/CXCL10 and CXCR3 not only attracts CXCR3+ T cells but also promotes the induction of IFNγ- high effector/cytotoxic CD4+ and CD8+ T cells, establishing a CXCL9/10-CXCR3-IFNγ self-amplifying cycle that promotes efficient cancer cell killing. One of the homeostatic mechanisms that may limit this cycle is the cleavage of the two N-terminal amino acids of these chemokines by Dipeptidyl Peptidase IV (DPP-4). The modified chemokines retain their ability to bind CXCR3 but no longer activate it, becoming competitive antagonists to native CXCL9/CXCL10. To develop a DPP-4-resistant variant, we combined biochemical analysis with computational modeling, demonstrating that the addition of N-terminal glutamine (Q) to CXCL9-Fc and CXCL10-Fc rendered them fully active CXCR3 agonists, yet resistant to DPP-4 cleavage. Preclinical evaluations imply that they offer significant therapeutic potential in cancer immunotherapy.
Molecular simulation-based investigation of thiazole derivatives as potential LasR inhibitors of Pseudomonas aeruginosa
Pseudomonas aeruginosa (P. aeruginosa), a very resilient pathogen, demonstrates a diverse array of virulence factors, the expression of which is closely linked to the quorum sensing(QS) mechanism, which facilitates cell-cell interaction. Quorum sensing (QS) inhibition is a promising strategy for combating bacterial infections. LasR, a transcriptional factor that controls the mechanism of QS in P. aeruginosa, is a promising target for therapeutic development, because a lot of research has been done on its structure. It has already been established that thiazoles and their compounds have anti-QS potential against P aeruginosa. The study aims to identify new LasR quorum sensing inhibitors (QSIs) derived from novel thiazoles utilizing a structure-based virtual screening technique using the ZINC database. A complete set of 800 molecules (a novel thiazole derivative library) were docked inside the active region of the LasR receptor before being screened using pharmacokinetic and toxicology studies. Among the derivatives that were examined, compounds D_152, D_153, and L_331 were selected as potential inhibitors of LasR in P. aeruginosa and further studied to obtain a crucial understanding of the binding interactions that take place between inhibitor ligands and LasR. The findings indicated that the pharmacophoric characteristics of the derivative D_152 were comparable to those of the reference thiazole molecule (TC). Moreover, the molecular docking investigations showed that derivative D_152 and reference compound TC both fit the LasR protein’s active area well. Furthermore, TC and D_152’s amino acid interaction graphs with LasR and CviR are nearly identical. Furthermore, compound D_152’s ability to engage with the LasR binding site through the dissolution of the protein’s dimer was demonstrated by molecular dynamics modeling tests conducted over a 50 ns time span, demonstrating its function as a LasR antagonist. Additionally, Density Functional Theory (DFT) study was conducted on compound D_152 in order to determine the electron density of a molecule. According to the research findings, the recently produced thiazole derivative (D_152) has the potential to be used as a QSI against the LasR receptor, which would speed up the fight against the pathogenicity of P. aeruginosa that is resistant to multiple drugs.
Evaluation of growth and development period according to spheno-occipital synchondrosis fusion stages in cone-beam computed tomography with ImageJ program
Quantifying the impact of biobanks and cohort studies
Biobanks advance biomedical and clinical research by collecting and offering data and biological samples for numerous studies. However, the impact of these repositories varies greatly due to differences in their purpose, scope, governance, and data collected. Here, we computationally identified 2,663 biobanks and their textual mentions in 228,761 scientific articles, 16,210 grants, 15,469 patents, 1,769 clinical trials, and 9,468 public policy documents, helping characterize the academic communities that utilize and support them. We found a strong concentration of biobank-related research on a few diseases, including obesity, Alzheimer’s disease, breast cancer, and diabetes. Moreover, collaboration, rather than citation count, shapes the community’s recognition of a biobank. We show that, on average, 41.1% of articles fail to reference any of the biobank’s reference papers, but 59.6% include a biobank member as a coauthor. Using a generalized linear model, we identified the key factors that contribute to the impact of a biobank, finding that an impactful biobank tends to be more open to external researchers and that quality data—especially linked medical records—as opposed to large data, correlates with a higher impact in science, innovation, and disease. The collected data and findings are accessible through an open-access web application intended to inform strategies to expand access and maximize the value of these resources.
Feasibility, acceptability, and effectiveness of group antenatal care on the continuum of care and perinatal outcomes in Sub-Saharan Africa: A systematic review and meta-analysis protocol
Introduction Women with adequate antenatal care (ANC) experience more reduction in adverse maternal and perinatal outcomes compared to those with insufficient care. However, the conventional individualized ANC models have not significantly improved perinatal outcomes. Comprehensive, woman-centered group ANC (G-ANC) interventions, integrating medical care with education, demonstrate positive effects on maternal and newborn health. While promising evidence exists in sub-Saharan Africa, the feasibility, acceptability, and effectiveness of G-ANC in resource-limited settings require further investigation. The variability in current studies further indicated the need for meta-analyses and systematic reviews to consolidate findings and clarify the overall effectiveness of G-ANC interventions. This synthesis aims to provide comprehensive evidence supporting the implementation of group prenatal care models in low-resource settings. Ultimately, it seeks to establish robust evidence to guide policy and practice, contributing to reduced maternal and perinatal mortality in the region. Methods and analysis This systematic review and meta-analysis protocol adheres to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocols guidelines. A comprehensive literature search will be conducted across multiple electronic databases, including PubMed/MEDLINE, Web of Science, EMBASE, and CINHAL, to identify pertinent articles published from January 1, 2016, to June 30, 2024. Experimental studies (pre-post, quasi-experimental study, cluster randomized controlled trial), prospective cohort design, prospective comparative study, and qualitative and mixed method designs will be included in the review. The Abstract and full-text screening will be conducted by three reviewers using Covidence, according to the eligibility criteria set. The Joanna Briggs Institute (JBI) Critical Appraisal Tools, specifically designed for JBI Systematic Reviews, will be utilized to assess the methodological quality of the included studies. Statistical heterogeneity will be assessed using the Higgins test. Meta-analysis will be conducted using R statistical software version 4.4.2, which will implement random effects models to determine the weights. Pre-specified subgroup analysis and sensitivity analysis will be performed as needed. The study results will be reported in order, starting with primary outcomes and then secondary outcomes and important subgroup outcomes analyses. Ethics and dissemination Ethical approval is not applicable as no original data will be collected. The findings of this review will be disseminated through publication and conference presentations. PROSPERO registration number CRD42024565501
Joint effects of air pollution and diet patterns on the risk of chronic obstructive pulmonary disease
A single mutation in an enteric virus alters tropism and sensitivity to microbiota
Many enteric viruses benefit from the microbiota. In mice, microbiota depletion reduces infection by noroviruses and picornaviruses. However, Reovirales viruses are outliers among enteric viruses. Rotavirus infection is inhibited by bacteria, and we determined that several reovirus strains have enhanced replication following microbiota depletion. Here, we focused on an isogenic pair of reoviruses that have opposing infection outcomes after microbiota depletion. Microbiota depletion reduces infection by reovirus strain T3SA+ but increases infection by strain T3SA−. These strains differ by a single amino acid polymorphism in the σ1 attachment protein, which confers sialic acid binding to T3SA+. Sialic acid binding facilitates T3SA+ infection of intestinal endothelial cells, while T3SA− inefficiently infects intestinal epithelial cells due to restriction by microbiota-driven, host-derived type III interferon responses. This study enhances an understanding of the interactions of enteric viruses, the microbiota, intestinal tropism, and antiviral responses.