Evolution of a large periplasmic disk in Campylobacterota flagella enables both efficient motility and autoagglutination.

The flagellar motors of Campylobacter jejuni (C. jejuni) and related Campylobacterota (previously epsilonproteobacteria) feature 100-nm-wide periplasmic "basal disks" that have been implicated in scaffolding a wider ring of additional motor proteins to increase torque, but the size of these disks is excessive for a role solely in scaffolding motor proteins. Here, we show that the basal disk is a flange that braces the flagellar motor during disentanglement of its flagellar filament from interactions with the cell body and other filaments. We show that motor output is unaffected when we shrink or displace the basal disk, and suppressor mutations of debilitated motors occur in flagellar-filament or cell-surface glycosylation pathways, thus sidestepping the need for a flange to overcome the interactions between two flagellar filaments and between flagellar filaments and the cell body. Our results identify unanticipated co-dependencies in the evolution of flagellar motor structure and cell-surface properties in the Campylobacterota.

Enhancing Transitions of Care: A Cross-Sectional Observational Study on the Role of Clinical Pharmacists in Transition Management in a Latin American Hospital.

Background The seamless management of transitions of care (TOC) is necessary for patient safety, as it directly correlates with a heightened risk of medication errors and adverse effects. Clinical pharmacists emerge as key stakeholders in optimizing medication management during TOC, specifically during hospital admission and discharge, through the implementation of innovative programs that contribute significantly to the mitigation of medication errors and improve patient satisfaction. Aim This study aims to assess the benefits of pharmacist-led interventions in a Costa Rican private hospital's TOC program for polymedicated and high-risk patients during admission and discharge by identifying and addressing medication errors. Methods A cross-sectional observational study was conducted at Clínica Biblica Hospital in San José, Costa Rica, from February 2022 to May 2023 and focused on polymedicated patients with chronic therapy and high-risk medications. The TOC Medication Program was specifically implemented to focus on medication reconciliation during the admission and discharge processes. A clinical pharmacist documented interventions based on discrepancies found within each patient's medication and assessed the economic impact of interventions on healthcare personnel during discharge by projecting potential complications in the absence of such interventions, a process that was validated by an internist physician. Results During the medication reconciliation at admission, medication discrepancies, mostly intentional omissions, were successfully addressed by clinical pharmacist interventions with a 90.2% acceptance rate during the admission process. At discharge, 18.9% of medications were high-risk, and nearly 40% of discharges were linked to drug-related problems (DRPs), prompting pharmaceutical interventions. The economic analysis indicated potential savings of $21,010.20 during discharge, demonstrating the substantial impact of interventions in preventing emergency service visits, specialist consults, and hospital admissions. Conclusion Pharmacist-led TOC programs offer important clinical advantages by effectively preventing and rectifying medication discrepancies. These discrepancies, if left unaddressed, pose a potential threat to patient safety. Moreover, the implementation of such programs demonstrates promising economic benefits.

Role of the Compression Ratio in Dual-Fuel Compression Ignition Combustion with Hydrogen and Methanol.

Renewable hydrogen and e-fuels, synthesized from captured CO2 and renewable H2, are feasible ways to achieve transport decarbonization, particularly in medium/heavy-duty applications and the maritime sector, where compression ignition engines predominate. Hydrogen and methanol are low carbon-intensive fuels, which can be used in these engines by carrying out dual-fuel combustion with a diesel-like fuel. Under low load engine conditions, reaching very high substitutions of the fossil diesel fuel can be a major challenge as the presence of these fuels affects negatively the autoignition process. Therefore, this work explores the substitution limits in dual-fuel mode with hydrogen and methanol under low load conditions (5.2 bar IMEP) for two different compression ratios (15.84:1 and 18.04:1) using a 1.13 L single-cylinder engine. Increasing the compression ratio allowed improvement of the maximum diesel substitution from 55 to 82% (also achieving a significant improvement of the thermal efficiency) with methanol and from 91 to 93% with H2 (but decreasing the thermal efficiency due to higher heat transfer losses).

Lipid imaging mass spectrometry: Towards a new molecular histology.

Lipid research is attracting greater attention, as these molecules are key components to understand cell metabolism and the connection between genotype and phenotype. The study of lipids has also been fueled by the development of new and powerful technologies, able to identify an increasing number of species in a single run and at decreasing concentrations. One of such key developments has been the image techniques that enable the visualization of lipid distribution over a tissue with cell resolution. Thanks to the spatial information reported by such techniques, it is possible to associate a lipidome trait to individual cells, in fixed metabolic stages, which greatly facilitates understanding the metabolic changes associated to diverse pathological conditions, such as cancer. Furthermore, the image of lipids is becoming a kind of new molecular histology that has great chances to make an impact in the diagnostic units of the hospitals. Here, we examine the current state of the technology and analyze what the next steps to bring it into the diagnosis units should be. To illustrate the potential and challenges of this technology, we present a case study on clear cell renal cell carcinoma, a good model for analyzing malignant tumors due to their significant cellular and molecular heterogeneity.

Integrative analysis of multi-omics data reveals importance of collagen and the PI3K AKT signalling pathway in CAKUT.

Congenital Anomalies of the Kidney and Urinary Tract (CAKUT) is the leading cause of childhood chronic kidney failure and a significant cause of chronic kidney disease in adults. Genetic and environmental factors are known to influence CAKUT development, but the currently known disease mechanism remains incomplete. Our goal is to identify affected pathways and networks in CAKUT, and thereby aid in getting a better understanding of its pathophysiology. With this goal, the miRNome, peptidome, and proteome of over 30 amniotic fluid samples of patients with non-severe CAKUT was compared to patients with severe CAKUT. These omics data sets were made findable, accessible, interoperable, and reusable (FAIR) to facilitate their integration with external data resources. Furthermore, we analysed and integrated the omics data sets using three different bioinformatics strategies: integrative analysis with mixOmics, joint dimensionality reduction and pathway analysis. The three bioinformatics analyses provided complementary features, but all pointed towards an important role for collagen in CAKUT development and the PI3K-AKT signalling pathway. Additionally, several key genes (CSF1, IGF2, ITGB1, and RAC1) and microRNAs were identified. We published the three analysis strategies as containerized workflows. These workflows can be applied to other FAIR data sets and help gaining knowledge on other rare diseases.

Emergence of cooperation in the one-shot Prisoner's dilemma through Discriminatory and Samaritan AIs.

As artificial intelligence (AI) systems are increasingly embedded in our lives, their presence leads to interactions that shape our behaviour, decision-making and social interactions. Existing theoretical research on the emergence and stability of cooperation, particularly in the context of social dilemmas, has primarily focused on human-to-human interactions, overlooking the unique dynamics triggered by the presence of AI. Resorting to methods from evolutionary game theory, we study how different forms of AI can influence cooperation in a population of human-like agents playing the one-shot Prisoner's dilemma game. We found that Samaritan AI agents who help everyone unconditionally, including defectors, can promote higher levels of cooperation in humans than Discriminatory AI that only helps those considered worthy/cooperative, especially in slow-moving societies where change based on payoff difference is moderate (small intensities of selection). Only in fast-moving societies (high intensities of selection), Discriminatory AIs promote higher levels of cooperation than Samaritan AIs. Furthermore, when it is possible to identify whether a co-player is a human or an AI, we found that cooperation is enhanced when human-like agents disregard AI performance. Our findings provide novel insights into the design and implementation of context-dependent AI systems for addressing social dilemmas.

The European Reference Genome Atlas: piloting a decentralised approach to equitable biodiversity genomics.

A genomic database of all Earth's eukaryotic species could contribute to many scientific discoveries; however, only a tiny fraction of species have genomic information available. In 2018, scientists across the world united under the Earth BioGenome Project (EBP), aiming to produce a database of high-quality reference genomes containing all ~1.5 million recognized eukaryotic species. As the European node of the EBP, the European Reference Genome Atlas (ERGA) sought to implement a new decentralised, equitable and inclusive model for producing reference genomes. For this, ERGA launched a Pilot Project establishing the first distributed reference genome production infrastructure and testing it on 98 eukaryotic species from 33 European countries. Here we outline the infrastructure and explore its effectiveness for scaling high-quality reference genome production, whilst considering equity and inclusion. The outcomes and lessons learned provide a solid foundation for ERGA while offering key learnings to other transnational, national genomic resource projects and the EBP.

Exploration of carvacrol aggregation by laser spectroscopy.

Carvacrol is an aromatic monoterpenoid found in thyme oil. Due to its implications for human health, it is important to elucidate its structure and its intramolecular interactions. We have characterised the carvacrol monomer, its complex with water, its dimer, and even its trimer in a supersonic expansion using mass-resolved laser spectroscopy techniques complemented by quantum-chemical computations. The resonance-enhanced multiphoton ionisation spectrum of the monomer features several transitions, which were assigned to the same conformer, confirmed by ion-dip infrared spectroscopy. However, a conclusive assignment of the infrared bands to one of the four conformations of carvacrol remains elusive. The experimental spectra for the monohydrated, the homodimer, and the homotrimer point to the detection of the lowest energy isomer in each case. Their structures are governed by a balance of intramolecular interactions, specifically hydrogen bonding and dispersion forces. Comparison with other similar systems demonstrates that dispersion interactions are key to the stabilisation of the aggregates, being present in all the structures. However, the hydrogen bonding is the dominant force as observed in the lowest-energy conformations.

Are suicides underreported? The impact of coroners versus medical examiners on suicide reporting.

OBJECTIVE: To evaluate if state death investigation systems affect the reporting of suicides, particularly when comparing medical examiners to coroners. DATA SOURCES AND STUDY SETTING: We used restricted-access state mortality data from National Vital Statistics System between the years 1959 to 2016. These data were matched with state-level changes in death investigation systems reported by the Centers for Disease Control and Prevention database on the Public Health Law Program: Coroner/ME Laws. STUDY DESIGN: We used difference-in-differences and event study methods for the analysis. We estimated the relative per capita changes in suicides, accidental deaths, and homicides when comparing coroner-only states with other death investigation types. Sub-analyses estimated differences by sex, race, and if coroners were required to receive training. DATA COLLECTION/EXTRACTION METHODS: Not Applicable. PRINCIPAL FINDINGS: Coroners-only states underreported suicides by 17.4% (p < 0.05) and performed 20.4% (p < 0.05) fewer autopsies compared to states with county coroners and a state medical examiner. This pattern is consistent by sex and race. Required coroner training did not affect death determination significantly. CONCLUSION: Coroners-only states underreported suicides compared to states with county coroners and a state medical examiner. The disparity in the use of autopsies is a potential mechanism for underreporting of suicides by coroners. If all coroners-only states adopted a state medical examiner, suicide reporting would increase by 2243-3100 deaths in the United States annually.

Distribution and habitat use patterns of the endangered Central American clouded oncilla (Leopardus pardinoides oncilla) in Costa Rica.

Montane cloud forests are highly threatened ecosystems that are vulnerable to climate change. These complex habitats harbor many species that suffer the negative consequences of this global phenomenon, such as shifts in their distribution and habitat use. The Central American clouded oncilla (Leopardus pardinoides oncilla) is the smallest and most endangered wild cat in Mesoamerica and is primarily reported in cloud forests throughout its distribution. The species is poorly understood, with no studies conducted in Central America assessing its habitat preferences. To bridge this knowledge gap, we sampled two mountain ranges in Costa Rica with camera traps and conducted an occupancy analysis to understand the anthropogenic and environmental features that influence oncilla habitat use within them. Additionally, we conducted spatial predictions of habitat use across its northern and southern range in Costa Rica to identify priority conservation areas for the species. We found that Central American clouded oncilla habitat use is driven primarily by environmental factors. Our results showed that oncillas select habitats with denser tree cover at high elevations, closer to permanent water sources, which may provide them with high prey density and a favorable habitat structure for their survival. Spatial predictions identified two main regions as conservation priority areas where threat mitigation efforts and monitoring should be implemented: the Caribbean slope of the Talamanca mountains, and the Arenal-Monteverde forest complex. The occupancy modeling approach turned out to be very useful to assess the spatial associations of the species with the environment and mapping the conservation priority areas. Future research and mitigation actions should focus on potential threats that could negatively impact Central American clouded oncilla populations and habitat use, including the role of mesopredators and feral species.

Diagnostic delay in patients from the international map of axial spondyloarthritis: geographic, socio-demographic and disease-related factors.

OBJECTIVES: To assess diagnostic delay and its associated factors globally, in a large sample of patients included in the International Map of Axial Spondyloarthritis (IMAS). METHODS: IMAS is a cross-sectional online survey (2017-2022) of 5,557 axSpA patients from 27 countries. Diagnostic delay was calculated as the difference between age at diagnosis and age at first symptom onset reported by patients. Associations between diagnostic delay and regions, sociodemographic characteristics, as well as disease-related factors were explored through univariable and multivariable linear regression analysis. RESULTS: Data from 5,327 patients who reported data on diagnostic delay in IMAS survey were analysed: 3,294 were from Europe, 752 from North America, 590 from Asia, 545 from Latin America, and 146 from Africa. Overall, patients reported a mean diagnostic delay of 7.4 years (median: 4.0) since symptom onset, with substantial variation across regions; being the highest delay in South Africa and the lowest in Asia. The variables associated with longer diagnostic delay in the final multivariable regression model were: younger age at symptom onset (b=-0.100), female gender (b = 2.274), being diagnosed by rheumatologist (b = 1.163), greater number of HCPs seen before diagnosis (b = 1.033), and history of uveitis (b = 1.286). CONCLUSION: In this global sample of axSpA patients, the mean diagnostic delay was 7.4 years, and showed significant differences across regions. Younger age at symptom onset, female gender, diagnosis made by a rheumatologist, greater number of HCPs seen before diagnosis, and the history of uveitis were the parameters associated with a longer diagnostic delay in axSpA patients.

Patient journey, disease burden, and functional disability in patients with axial spondyloarthritis in South Africa: results of International Map of Axial Spondyloarthritis (IMAS).

OBJECTIVE: To assess the unmet needs of South Africans with axial spondyloarthritis (axSpA) focusing on the patient journey, functional disability, and health-related quality of life. METHODS: One hundred forty-six South African axSpA patients completed the International Map of Axial Spondyloarthritis (IMAS) online survey. Patient journey, functional disability, activities of daily living, and psychological stress were analyzed in relation to socio-demographic characteristics, disease activity, diagnostic delay, extra-musculoskeletal manifestations, and drug therapy. RESULTS: Majority were female (82.2%) and Caucasian (89.7%) and the mean age of participants, age at onset of initial symptoms, and diagnostic delay were 44.7, 26.7, and 10.8 years, respectively. Participants reported a mean of 3.4 visits to healthcare professionals prior to a definitive diagnosis of axSpA, mostly made by rheumatologists (77.9%). Active disease (BASDAI ≥ 4) was reported by 87%, 69.9% suffered from psychological distress (general health questionnaire-12 score ≥ 3), and more than two-thirds suffered functional limitations in daily, personal, and social activities. Multivariable logistic analysis showed that active disease was more common in females [OR (95% CI) = 4.3 (1.2-15.2)] and was associated with greater functional limitation [OR (95% CI) = 1.1 (1.0-1.2)]. CONCLUSION: Of all the regions assessed in the IMAS (n = 5557 participants, 27 countries), South Africans reported the longest delay in diagnosis. The South African patient journey depicts a process burdened with diagnostic challenges and delays, coupled with patients experiencing significant personal and social limitations. These results emphasize the urgent need to establish local diagnostic and treatment guidelines for axSpA in South Africa, to reduce diagnostic delay, and to control disease activity associated with functional limitation in axSpA. Key Points • Axial spondyloarthritis (axSpA) in South Africans is associated with significant limitations in physical, mental, and social functioning. • First study to describe the unmet needs of South African patients with axSpA.

Staurosporine as a Potential Treatment for Acanthamoeba Keratitis Using Mouse Cornea as an Ex Vivo Model.

Acanthamoeba is a ubiquitous genus of amoebae that can trigger a severe and progressive ocular disease known as Acanthamoeba Keratitis (AK). Furthermore, current treatment protocols are based on the combination of different compounds that are not fully effective. Therefore, an urgent need to find new compounds to treat Acanthamoeba infections is clear. In the present study, we evaluated staurosporine as a potential treatment for Acanthamoeba keratitis using mouse cornea as an ex vivo model, and a comparative proteomic analysis was conducted to elucidate a mechanism of action. The obtained results indicate that staurosporine altered the conformation of actin and tubulin in treated trophozoites of A. castellanii. In addition, proteomic analysis of treated trophozoites revealed that this molecule induced overexpression and a downregulation of proteins related to key functions for Acanthamoeba infection pathways. Additionally, the ex vivo assay used validated this model for the study of the pathogenesis and therapies of AK. Finally, staurosporine eliminated the entire amoebic population and prevented the adhesion and infection of amoebae to the epithelium of treated mouse corneas.

The Structure of Cilium Inner Junctions Revealed by Electron Cryo-tomography.

The cilium is a microtubule-based organelle critical for many cellular functions. Its assembly initiates at a basal body and continues as an axoneme that projects out of the cell to form a functional cilium. This assembly process is tightly regulated. However, our knowledge of the molecular architecture and the mechanism of assembly is limited. By applying electron cryotomography and subtomogram averaging, we obtained subnanometer resolution structures of the inner junction in three distinct regions of the cilium: the proximal region of the basal body, the central core of the basal body, and the flagellar axoneme. The structures allowed us to identify several basal body and axoneme components. While a few proteins are distributed throughout the entire length of the organelle, many are restricted to particular regions of the cilium, forming intricate local interaction networks and bolstering local structural stability. Finally, by knocking out a critical basal body inner junction component Poc1, we found the triplet MT was destabilized, resulting in a defective structure. Surprisingly, several axoneme-specific components were found to "infiltrate" into the mutant basal body. Our findings provide molecular insight into cilium assembly at its inner Junctions, underscoring its precise spatial regulation.

Initial Upper Palaeolithic lithic industry at Cueva Millán in the hinterlands of Iberia.

The extended period of coexistence between Neanderthals and Homo sapiens in Europe coincided with the emergence of regionally distinctive lithic industries, signalling the onset of the Upper Palaeolithic. The Iberian Peninsula was on the periphery of pioneering Upper Palaeolithic developments, with archaeological remains primarily found in northern territories. We report the discovery of an initial Upper Palaeolithic lithic industry at Cueva Millán in the hinterlands of Iberia. This industry, termed here Arlanzian, not only represents the earliest and southernmost evidence of such industries in Iberia but also lacks a direct counterpart. However, it exhibits chronological and technological parallels with the lithic industries associated with the earliest expansion of Homo sapiens throughout Eurasia. We interpret this as potential evidence of its intrusive nature, but not necessarily associated with a migration event, as more complex scenarios derived from inter-population connectivity must be also considered. The biological identity of the Arlanzian makers remains unknown, but they coexisted with declining Neanderthal groups from neighbouring territories.

Influence of Hydrogel and Zinc Oxide Nanoparticles on the Germination and Establishment of Chenopodium quinoa.

The aim of this study was to assess the influence of hydrogel and zinc oxide nanoparticles on quinoa germination and establishment. Various doses of a commercial potassium-based hydrogel (0, 5, 7, and 9 g), each dissolved in one liter of rainwater, were applied. Additionally, 1.5 g of zinc oxide nanoparticles (ZnO-NP) and pre-crushed nitrogen fertilizer, at a rate of 1.6 kg/ha, were added to the solution to achieve a homogeneous mixture. Following the application of hydrogel in the 10-linear-meter rows corresponding to each treatment area in every block, 25 seeds per linear meter of the "Blanca de Juli" quinoa cultivar were sown with a 4 cm spacing between the seeds. Subsequently, a thin layer of soil, approximately 0.5 cm thick, was used to cover the seeds. Ten seedlings were randomly selected and labeled for subsequent evaluations. The experimental design employed in this research was a completely randomized block design. The collected data underwent an analysis of variance, and the means of all the treatments were compared using Tukey's test with a 5% probability. Height and diameter evaluations of the plant neck were conducted every 45 days. The doses used in this study (5, 7, and 9 g of hydrogel per liter of water) significantly enhanced seed germination and increased the number of plants per linear meter (from 82.00 to 90.33) compared to the control dose without hydrogel (14.66), which resulted in an average of one plant per linear meter.

Social Anxiety Profiles and Psychopathological Symptom Differences in Spanish Adolescents.

Research on social anxiety (SA) over the years has revealed its associations with different psychopathological symptoms. This study aims to characterize SA profiles in a sample of Spanish adolescents and explore their differences in psychopathological symptoms. Data from 1,288 Spanish students in the 15 to 18 age range (M = 16.30, SD = 0.97, 47.5% female) were collected using random cluster sampling. The Social Anxiety Scale for Adolescents (SAS-A) and the Symptom Assessment-45 Questionnaire (SA-45) were employed. Four SA profiles were revealed by the Latent Profile Analysis (LPA): extreme SA, high SA, moderate SA, and low SA. Statistically significant differences in psychopathological symptoms were revealed by the MANOVA (effect sizes from d = -2.13 to d = -0.37). The extreme SA profile exhibited the most severe psychopathological symptoms, whereas the low SA profile displayed the mildest manifestations. Proposed interventions aim to support adolescents with SA risk profiles.

Report of an unusual association of Oropouche Fever with Guillain-Barré syndrome in Cuba, 2024.

Oropouche virus is the aetiological agent of Oropouche fever. At present, this is currently considered one of the most important vector-borne diseases in Latin America. On 27 May 2024, the Ministry of Public Health of Cuba reported the first ever outbreak of Oropouche fever. In this report, we describe three human cases of Oropouche virus infection with symptoms and signs of neurological disease and clinical diagnosis of Guillain-Barré Syndrome. This study offers insights regarding that Oropouche virus is a causal agent of neurological disorders and it could be involved in the etiology of the Guillain-Barré Syndrome.

Recording provenance of workflow runs with RO-Crate.

Recording the provenance of scientific computation results is key to the support of traceability, reproducibility and quality assessment of data products. Several data models have been explored to address this need, providing representations of workflow plans and their executions as well as means of packaging the resulting information for archiving and sharing. However, existing approaches tend to lack interoperable adoption across workflow management systems. In this work we present Workflow Run RO-Crate, an extension of RO-Crate (Research Object Crate) and Schema.org to capture the provenance of the execution of computational workflows at different levels of granularity and bundle together all their associated objects (inputs, outputs, code, etc.). The model is supported by a diverse, open community that runs regular meetings, discussing development, maintenance and adoption aspects. Workflow Run RO-Crate is already implemented by several workflow management systems, allowing interoperable comparisons between workflow runs from heterogeneous systems. We describe the model, its alignment to standards such as W3C PROV, and its implementation in six workflow systems. Finally, we illustrate the application of Workflow Run RO-Crate in two use cases of machine learning in the digital image analysis domain.