Gender trends at the annual Spanish Urologic Association (AEU) meeting: A review of AEU programmes over a 10-year period (2012-2022).

INTRODUCTION: Gender equity in urological meetings is pivotal for fostering diversity and inclusivity in the field. This study aims to evaluate the representation of Spanish urologist and regional disparities, and to assess its alignment with the demographic composition of the urological community. MATERIALS AND METHODS: All urology meetings organized by the AEU between January 2012 and December 2022 were reviewed, including meeting information and details of the faculty. Additionally, we analysed geographic distribution of speakers across 17 different regions. Gender demographics were obtained disaggregating data by sex and year from the Organización Médica Colegial de España (OMC) and from those urologists affiliated to the AEU. RESULTS: Analysing 52 AEU congresses held from 2012 to 2022, encompassing 3,407 speakers, the study found that 95.25% of speakers were from Spain and 89.6% were male speakers. Over the years, there was a positive trend in female speaker representation, increasing by 1.1% annually, slightly lagging the 1.8% annual rise in the number of female urologists in Spain. In specific subfields like functional, transplantation, and oncology sessions, the study revealed a higher representation of women, indicating focused efforts in these areas. Geographically, Madrid, Catalonia and Andalusia exhibited the highest representation. CONCLUSIONS: Although there was a positive trend towards an increased participation of female urologists in Spanish urological meetings, it fails to accurately reflect the proportional increase in the number of women entering the urology profession in recent years. This study underscores the importance of ongoing efforts to ensure diverse and balanced representation in urological forum.

CD39 is expressed on functional effector and tissue resident memory CD8+ T cells.

The ecto-ATPase CD39 is expressed on exhausted CD8+ T cells in chronic viral infection and has been proposed as a marker of tumor-specific CD8+ T cells in cancer, but the role of CD39 in an effector and memory T cell response has not been clearly defined. We report that CD39 is expressed on antigen-specific CD8+ short-lived effector cells (SLECs), while it's co-ecto-enzyme, CD73, is found on memory precursor effector cells (MPEC) in vivo . Inhibition of CD39 enzymatic activity during in vitro T cell priming enhances MPEC differentiation in vivo after transfer and infection. The enriched MPEC phenotype is associated with enhanced tissue resident memory (T RM ) establishment in the brain and salivary gland following an acute intranasal viral infection, suggesting that CD39 ATPase activity plays a role in memory CD8+ T cell differentiation. We also show that CD39 is expressed on human and murine T RM across several non-lymphoid tissues and melanoma, while CD73 is expressed on both circulating and resident memory subsets in mice. In contrast to exhausted CD39+ T cells in chronic infection, CD39+ T RM are fully functional when stimulated ex vivo with cognate antigen. This work further expands the identity of CD39 beyond a T cell exhaustion marker.

Worldwide forest surveys reveal forty-three new species in Phytophthora major Clade 2 with fundamental implications for the evolution and biogeography of the genus and global plant biosecurity.

During 25 surveys of global Phytophthora diversity, conducted between 1998 and 2020, 43 new species were detected in natural ecosystems and, occasionally, in nurseries and outplantings in Europe, Southeast and East Asia and the Americas. Based on a multigene phylogeny of nine nuclear and four mitochondrial gene regions they were assigned to five of the six known subclades, 2a-c, e and f, of Phytophthora major Clade 2 and the new subclade 2g. The evolutionary history of the Clade appears to have involved the pre-Gondwanan divergence of three extant subclades, 2c, 2e and 2f, all having disjunct natural distributions on separate continents and comprising species with a soilborne and aquatic lifestyle and, in addition, a few partially aerial species in Clade 2c; and the post-Gondwanan evolution of subclades 2a and 2g in Southeast/East Asia and 2b in South America, respectively, from their common ancestor. Species in Clade 2g are soilborne whereas Clade 2b comprises both soil-inhabiting and aerial species. Clade 2a has evolved further towards an aerial lifestyle comprising only species which are predominantly or partially airborne. Based on high nuclear heterozygosity levels ca. 38 % of the taxa in Clades 2a and 2b could be some form of hybrid, and the hybridity may be favoured by an A1/A2 breeding system and an aerial life style. Circumstantial evidence suggests the now 93 described species and informally designated taxa in Clade 2 result from both allopatric non-adaptive and sympatric adaptive radiations. They represent most morphological and physiological characters, breeding systems, lifestyles and forms of host specialism found across the Phytophthora clades as a whole, demonstrating the strong biological cohesiveness of the genus. The finding of 43 previously unknown species from a single Phytophthora clade highlight a critical lack of information on the scale of the unknown pathogen threats to forests and natural ecosystems, underlining the risk of basing plant biosecurity protocols mainly on lists of named organisms. More surveys in natural ecosystems of yet unsurveyed regions in Africa, Asia, Central and South America are needed to unveil the full diversity of the clade and the factors driving diversity, speciation and adaptation in Phytophthora. Taxonomic novelties: New species: Phytophthora amamensis T. Jung, K. Kageyama, H. Masuya & S. Uematsu, Phytophthora angustata T. Jung, L. Garcia, B. Mendieta-Araica, & Y. Balci, Phytophthora balkanensis I. Milenkovic, Z. Tomic, T. Jung & M. Horta Jung, Phytophthora borneensis T. Jung, A. Durán, M. Tarigan & M. Horta Jung, Phytophthora calidophila T. Jung, Y. Balci, L. Garcia & B. Mendieta-Araica, Phytophthora catenulata T. Jung, T.-T. Chang, N.M. Chi & M. Horta Jung, Phytophthora celeris T. Jung, L. Oliveira, M. Tarigan & I. Milenkovic, Phytophthora curvata T. Jung, A. Hieno, H. Masuya & M. Horta Jung, Phytophthora distorta T. Jung, A. Durán, E. Sanfuentes von Stowasser & M. Horta Jung, Phytophthora excentrica T. Jung, S. Uematsu, K. Kageyama & C.M. Brasier, Phytophthora falcata T. Jung, K. Kageyama, S. Uematsu & M. Horta Jung, Phytophthora fansipanensis T. Jung, N.M. Chi, T. Corcobado & C.M. Brasier, Phytophthora frigidophila T. Jung, Y. Balci, K. Broders & I. Milenkovic, Phytophthora furcata T. Jung, N.M. Chi, I. Milenkovic & M. Horta Jung, Phytophthora inclinata N.M. Chi, T. Jung, M. Horta Jung & I. Milenkovic, Phytophthora indonesiensis T. Jung, M. Tarigan, L. Oliveira & I. Milenkovic, Phytophthora japonensis T. Jung, A. Hieno, H. Masuya & J.F. Webber, Phytophthora limosa T. Corcobado, T. Majek, M. Ferreira & T. Jung, Phytophthora macroglobulosa H.-C. Zeng, H.-H. Ho, F.-C. Zheng & T. Jung, Phytophthora montana T. Jung, Y. Balci, K. Broders & M. Horta Jung, Phytophthora multipapillata T. Jung, M. Tarigan, I. Milenkovic & M. Horta Jung, Phytophthora multiplex T. Jung, Y. Balci, K. Broders & M. Horta Jung, Phytophthora nimia T. Jung, H. Masuya, A. Hieno & C.M. Brasier, Phytophthora oblonga T. Jung, S. Uematsu, K. Kageyama & C.M. Brasier, Phytophthora obovoidea T. Jung, Y. Balci, L. Garcia & B. Mendieta-Araica, Phytophthora obturata T. Jung, N.M. Chi, I. Milenkovic & M. Horta Jung, Phytophthora penetrans T. Jung, Y. Balci, K. Broders & I. Milenkovic, Phytophthora platani T. Jung, A. Pérez-Sierra, S.O. Cacciola & M. Horta Jung, Phytophthora proliferata T. Jung, N.M. Chi, I. Milenkovic & M. Horta Jung, Phytophthora pseudocapensis T. Jung, T.-T. Chang, I. Milenkovic & M. Horta Jung, Phytophthora pseudocitrophthora T. Jung, S.O. Cacciola, J. Bakonyi & M. Horta Jung, Phytophthora pseudofrigida T. Jung, A. Durán, M. Tarigan & M. Horta Jung, Phytophthora pseudoccultans T. Jung, T.-T. Chang, I. Milenkovic & M. Horta Jung, Phytophthora pyriformis T. Jung, Y. Balci, K.D. Boders & M. Horta Jung, Phytophthora sumatera T. Jung, M. Tarigan, M. Junaid & A. Durán, Phytophthora transposita T. Jung, K. Kageyama, C.M. Brasier & H. Masuya, Phytophthora vacuola T. Jung, H. Masuya, K. Kageyama & J.F. Webber, Phytophthora valdiviana T. Jung, E. Sanfuentes von Stowasser, A. Durán & M. Horta Jung, Phytophthora variepedicellata T. Jung, Y. Balci, K. Broders & I. Milenkovic, Phytophthora vietnamensis T. Jung, N.M. Chi, I. Milenkovic & M. Horta Jung, Phytophthora ×australasiatica T. Jung, N.M. Chi, M. Tarigan & M. Horta Jung, Phytophthora ×lusitanica T. Jung, M. Horta Jung, C. Maia & I. Milenkovic, Phytophthora ×taiwanensis T. Jung, T.-T. Chang, H.-S. Fu & M. Horta Jung. Citation: Jung T, Milenkovic I, Balci Y, Janousek J, Kudlácek T, Nagy ZÁ, Baharuddin B, Bakonyi J, Broders KD, Cacciola SO, Chang T-T, Chi NM, Corcobado T, Cravador A, Dordevic B, Durán A, Ferreira M, Fu C-H, Garcia L, Hieno A, Ho H-H, Hong C, Junaid M, Kageyama K, Kuswinanti T, Maia C, Májek T, Masuya H, Magnano di San Lio G, Mendieta-Araica B, Nasri N, Oliveira LSS, Pane A, Pérez-Sierra A, Rosmana A, Sanfuentes von Stowasser E, Scanu B, Singh R, Stanivukovic Z, Tarigan M, Thu PQ, Tomic Z, Tomsovský M, Uematsu S, Webber JF, Zeng H-C, Zheng F-C, Brasier CM, Horta Jung M (2024). Worldwide forest surveys reveal forty-three new species in Phytophthora major Clade 2 with fundamental implications for the evolution and biogeography of the genus and global plant biosecurity. Studies in Mycology 107: 251-388. doi: 10.3114/sim.2024.107.04.

Brain signal variability and executive functions across the life span.

Neural variability is thought to facilitate survival through flexible adaptation to changing environmental demands. In humans, such capacity for flexible adaptation may manifest as fluid reasoning, inhibition of automatic responses, and mental set-switching-skills falling under the broad domain of executive functions that fluctuate over the life span. Neural variability can be quantified via the BOLD signal in resting-state fMRI. Variability of large-scale brain networks is posited to underpin complex cognitive activities requiring interactions between multiple brain regions. Few studies have examined the extent to which network-level brain signal variability across the life span maps onto high-level processes under the umbrella of executive functions. The present study leveraged a large publicly available neuroimaging dataset to investigate the relationship between signal variability and executive functions across the life span. Associations between brain signal variability and executive functions shifted as a function of age. Limbic-specific variability was consistently associated with greater performance across subcomponents of executive functions. Associations between executive function subcomponents and network-level variability of the default mode and central executive networks, as well as whole-brain variability, varied across the life span. Findings suggest that brain signal variability may help to explain to age-related differences in executive functions across the life span.

Traditionally, regional variability in brain signals has been viewed as a source of noise in human neuroimaging research. Our study demonstrates that brain signal variability may contain meaningful information related to psychological processes. We demonstrate that brain signal variability, particularly whole-brain variability, may serve as a reliable indicator of cognitive functions across the life span. Global variability and network-level variability play differing roles in supporting executive functions. Findings suggest that brain signal variability serves as a meaningful indicator of development and cognitive aging.

Applying elastic resistance bands for gait training: A simulation-based study to determine how band configuration affects gait biomechanics and muscle activation.

BACKGROUND: Wearable robotic exoskeletons and leg braces are desirable for gait rehabilitation because they can apply loads directly to an affected joint. Yet, they are not widely used in clinics because they are costly and complex to set up. Conversely, tethered devices, such as elastic resistance bands, are widely available in clinics, are low-cost, and are quick to set up. However, resistance bands will affect walking differently based on how they are configured to pull on the leg (e.g., pulling forward or backward). RESEARCH QUESTION: How can a resistance band be configured to alter muscle activation and gait biomechanics based on the segment it is attached to and the angle with which it attaches? METHODS: We used an open-source musculoskeletal modeling platform to emulate several configurations of an elastic band pulling on the ankle, calf, and thigh at various angles during non-pathological walking. We evaluated gait biomechanics and simulated muscle activation using computed muscle control (CMC) and identified a subset of four configurations with potential applications for gait training. Eight non-pathological participants then walked on a treadmill under these configurations to verify how these configurations altered muscle activation. RESULTS: We found that muscle activity greatly varied based on the location where the elastic band is attached and the angle with which the elastic band pulls on the leg. Notably, specific angles can be used to pull on the legs to elicit an increase or decrease in muscle activation. SIGNIFICANCE: This study provides insight into how tethered devices can be configured to provide assistance or resistance during gait training. This information can be applied when developing low-cost gait training solutions for addressing individuals' impairments.

The Monarch Initiative in 2024: an analytic platform integrating phenotypes, genes and diseases across species.

Bridging the gap between genetic variations, environmental determinants, and phenotypic outcomes is critical for supporting clinical diagnosis and understanding mechanisms of diseases. It requires integrating open data at a global scale. The Monarch Initiative advances these goals by developing open ontologies, semantic data models, and knowledge graphs for translational research. The Monarch App is an integrated platform combining data about genes, phenotypes, and diseases across species. Monarch's APIs enable access to carefully curated datasets and advanced analysis tools that support the understanding and diagnosis of disease for diverse applications such as variant prioritization, deep phenotyping, and patient profile-matching. We have migrated our system into a scalable, cloud-based infrastructure; simplified Monarch's data ingestion and knowledge graph integration systems; enhanced data mapping and integration standards; and developed a new user interface with novel search and graph navigation features. Furthermore, we advanced Monarch's analytic tools by developing a customized plugin for OpenAI's ChatGPT to increase the reliability of its responses about phenotypic data, allowing us to interrogate the knowledge in the Monarch graph using state-of-the-art Large Language Models. The resources of the Monarch Initiative can be found at monarchinitiative.org and its corresponding code repository at github.com/monarch-initiative/monarch-app.

High-throughput analysis of glycan sorting into extracellular vesicles.

Extracellular vesicles (EVs) are cell-released vesicles that mediate intercellular communication by transferring bioactive cargo. Protein and RNA sorting into EVs has been extensively assessed, while selective enrichment of glycans in EVs remains less explored. In this study, a mass spectrometry-based approach, glycan node analysis (GNA), was applied to broadly assess the sorting of glycan features into EVs. Two metastatic variants (lung and bone) generated in mouse modes from the MDA-MB-231 human breast cancer cell line were assessed, as these EVs are known to contain distinct organotropic biomolecules. EVs were isolated from conditioned cell culture medium by tangential flow filtration and authenticated by standard techniques. GNA analysis revealed selective enrichment of several glycan features in EVs compared to the originating cells, particularly those associated with binding to the extracellular matrix, which was also observed in EVs from the parental MDA-MB-231 cell line (human pleural metastases). The bone-tropic variant displayed enrichment of distinct EV glycan features compared to the lung-tropic one. Additionally, the metastatic variants generated in mouse models displayed reduced EV glycan sorting compared to the parental metastatic cell line. This study represents the first comprehensive assessment of differences in glycan features between EVs and originating cells and provides evidence that the diversity of EV glycan sorting is reduced upon generation of variant cell lines in mouse models. Future research is likely to uncover novel mechanisms of EV glycan sorting, shed light on glycan features for EV authentication or biomarker purposes, and assess functional roles of the EV glycocode in (patho)physiology.

Global reward processing deficits predict negative symptoms transdiagnostically and transphasically in a severe mental illness-spectrum sample.

Reward processing impairments are a key factor associated with negative symptoms in those with severe mental illnesses. However, past findings are inconsistent regarding which reward processing components are impaired and most strongly linked to negative symptoms. The current study examined the hypothesis that these mixed findings may be the result of multiple reward processing pathways (i.e., equifinality) to negative symptoms that cut across diagnostic boundaries and phases of illness. Participants included healthy controls (n = 100) who served as a reference sample and a severe mental illness-spectrum sample (n = 92) that included psychotic-like experiences, clinical high-risk for psychosis, bipolar disorder, and schizophrenia participants. All participants completed tasks measuring four RDoC Positive Valence System constructs: value representation, reinforcement learning, effort-cost computation, and hedonic reactivity. A k-means cluster analysis of the severe mental illness-spectrum samples identified three clusters with differential reward processing profiles that were characterized by: (1) global reward processing deficits (22.8%), (2) selective impairments in hedonic reactivity alone (40.2%), and (3) preserved reward processing (37%). Elevated negative symptoms were only observed in the global reward processing cluster. All clusters contained participants from each clinical group, and the distribution of these groups did not significantly differ among the clusters. Findings identified one pathway contributing to negative symptoms that was transdiagnostic and transphasic. Future work further characterizing divergent pathways to negative symptoms may help to improve symptom trajectories and personalized treatments.

Telemedicine in the management of patients with headache: current situation and recommendations of the Spanish Society of Neurology's Headache Study Group.

INTRODUCTION: The COVID-19 pandemic has caused an unexpected boost to telemedicine. We analyse the impact of the pandemic on telemedicine applied in Spanish headache consultations, review the literature, and issue recommendations for the implementation of telemedicine in consultations. METHOD: The study comprised 3 phases: 1) review of the MEDLINE database since 1958 (first reported experience with telemedicine); 2) Google Forms survey sent to all members of the Spanish Society of Neurology's Headache Study Group (GECSEN); and 3) online consensus of GECSEN experts to issue recommendations for the implementation of telemedicine in Spain. RESULTS: COVID-19 has increased waiting times for face-to-face consultations, increasing the use of all telemedicine modalities: landline telephone (from 75% before April 2020 to 97% after), mobile telephone (from 9% to 27%), e-mail (from 30% to 36%), and video consultation (from 3% to 21%). Neurologists are aware of the need to expand the availability of video consultations, which are clearly growing, and other e-health and m-health tools. CONCLUSIONS: The GECSEN recommends and encourages all neurologists who assist patients with headaches to implement telemedicine resources, with the optimal objective of offering video consultation to patients under 60-65 years of age and telephone calls to older patients, although each case must be considered on an individual basis. Prior approval and advice must be sought from legal and IT services and the centre's management. Most patients with stable headache and/or neuralgia are eligible for telemedicine follow-up, after a first consultation that must always be held in person.

Effect of air pollutants on ambulatory blood pressure.

BACKGROUND AND METHODOLOGY: Air pollutants have a significant impact on public health. The aim of the study was to find out the relationship between ambulatory blood pressure measured by 24-h ambulatory blood pressure monitoring (ABPM) and the atmospheric pollutants that are measured regularly (PM10, PM2.5, NO2 and SO2). An observational study of temporal and geographic measurements of individual patients (case-time series design) was carried out in Primary Care Centres and Hypertension Units in the Barcelona metropolitan area. We included 2888 hypertensive patients≥18 years old, untreated, with a first valid ABPM performed between 2005 and 2014 and with at least one air pollution station within a radius of <3km. RESULTS AND CONCLUSIONS: The mean age was 54.3 (SD 14.6) years. 50.1% were women and 16.9% of the sample were smokers. Mean 24-h blood pressure (BP) was 128.0 (12.7)/77.4 (9.7) mmHg. After adjusting for mean ambient temperature and different risk factors, a significant association was found between ambulatory diastolic BP (DBP) and PM10 concentrations the day before ABPM. For each increase of 10µg/m3 of PM10, an increase of 1.37mmHg 24-h DBP and 1.48mmHg daytime DBP was observed. No relationship was found between PM2.5, NO2 and SO2 and ambulatory BP, nor between any pollutant and clinical BP. The concentration of PM10 the day before the ABPM is significantly associated with an increase in 24-h DBP and daytime DBP.

Lactobacillus rhamnosus GG administration partially prevents diet-induced insulin resistance in rats: a comparison with its heat-inactivated parabiotic.

Insulin resistance and type 2 diabetes are obesity-related health alterations, featuring an ever-increasing prevalence. Besides inadequate feeding patterns, gut microbiota alterations stand out as potential contributors to these metabolic disturbances. The aim of this study was to investigate whether the administration of a probiotic (Lactobacillus rhamnosus GG) effectively prevents diet-induced insulin resistance in rats and to compare these potential effects with those exerted by its heat-inactivated parabiotic. For this purpose, 34 male Wistar rats were fed a standard or a high-fat high-fructose diet, alone or supplemented with viable or heat-inactivated Lactobacillus rhamnosus GG. The body and white adipose tissue weight increases, induced by the obesogenic diet, were prevented by probiotic and parabiotic administration. The trend towards higher basal glucose levels and significantly higher serum insulin concentration observed in the non-treated animals fed with the obesogenic diet were effectively reverted by both treatments. Similar results were also found for serum adiponectin and leptin, whose levels were brought back by the probiotic and parabiotic administration to values similar to those of the control animals. Noteworthily, parabiotic administration significantly reduced skeletal muscle triglyceride content and activated CPT-1b compared to the non-treated animals. Finally, both treatments enhanced Akt and AS160 phosphorylation in the skeletal muscle compared to the non-treated animals; however, only parabiotic administration increased GLUT-4 protein expression in this tissue. These results suggest that heat-inactivated Lactobacillus rhamnosus GG seem to be more effective than its probiotic of origin in preventing high-fat high-fructose diet-induced insulin resistance in rats.

Effect of air pollutants on ambulatory blood pressure / Efectos de los contaminantes aéreos en la presión arterial ambulatoria

Background and methodology: Air pollutants have a significant impact on public health. The aim of the study was to find out the relationship between ambulatory blood pressure measured by 24-h ambulatory blood pressure monitoring (ABPM) and the atmospheric pollutants that are measured regularly (PM10, PM2.5, NO2 and SO2). An observational study of temporal and geographic measurements of individual patients (case-time series design) was carried out in Primary Care Centres and Hypertension Units in the Barcelona metropolitan area. We included 2888 hypertensive patients≥18 years old, untreated, with a first valid ABPM performed between 2005 and 2014 and with at least one air pollution station within a radius of <3km. Results and conclusions: The mean age was 54.3 (SD 14.6) years. 50.1% were women and 16.9% of the sample were smokers. Mean 24-h blood pressure (BP) was 128.0 (12.7)/77.4 (9.7) mmHg. After adjusting for mean ambient temperature and different risk factors, a significant association was found between ambulatory diastolic BP (DBP) and PM10 concentrations the day before ABPM. For each increase of 10μg/m3 of PM10, an increase of 1.37mmHg 24-h DBP and 1.48mmHg daytime DBP was observed. No relationship was found between PM2.5, NO2 and SO2 and ambulatory BP, nor between any pollutant and clinical BP. The concentration of PM10 the day before the ABPM is significantly associated with an increase in 24-h DBP and daytime DBP. (AU)

Antecedentes y metodología: Los contaminantes aéreos tienen un impacto importante en la salud pública. El objetivo del estudio era conocer la relación entre la presión arterial ambulatoria medida mediante monitorización ambulatoria de la presión arterial (MAPA) de 24h y los contaminantes atmosféricos que se miden regularmente (PM10, PM2,5, NO2 y SO2). Se realizó un estudio observacional de medidas temporales y geográficas de pacientes individuales (case-time series design) en centros de atención primaria y unidades de hipertensión del área metropolitana de Barcelona. Se incluyeron 2.888 pacientes hipertensos≥18 años, no tratados, con una primera MAPA válida realizada entre 2005-2014 y al menos con una estación de contaminación atmosférica en un radio<3km. Resultados y conclusiones: La media de edad fue de 54,3 (DE 14,6) años. El 50,1% eran mujeres y el 16,9% de la muestra eran fumadores. La presión arterial (PA) de 24h fue de 128,0 (12,7)/77,4 (9,7)mmHg. Tras ajustarse por la temperatura ambiental media y por los diferentes factores de riesgo se halló una asociación significativa entre PA diastólica (PAD) ambulatoria y las concentraciones de PM10 del día anterior a la MAPA. Por cada incremento de 10μg/m3 de PM10 se observaba un aumento de 1,37mmHg PAD 24h y de 1,48mmHg PAD diurna. No se halló relación entre PM2,5, NO2 y SO2 y PA ambulatoria, ni entre ningún contaminante y PA clínica. La concentración de PM10 del día anterior a la realización de la MAPA se asocia significativamente con un aumento de PAD 24h y PAD diurna. (AU)

Reconstituted Extracellular Vesicles from Human Platelets Decrease Viral Myocarditis in Mice.

Patients with viral myocarditis are at risk of sudden death and may progress to dilated cardiomyopathy (DCM). Currently, no disease-specific therapies exist to treat viral myocarditis. Here it is examined whether reconstituted, lyophilized extracellular vesicles (EVs) from platelets from healthy men and women reduce acute or chronic myocarditis in male mice. Human-platelet-derived EVs (PEV) do not cause toxicity, damage, or inflammation in naïve mice. PEV administered during the innate immune response significantly reduces myocarditis with fewer epidermal growth factor (EGF)-like module-containing mucin-like hormone receptor-like 1 (F4/80) macrophages, T cells (cluster of differentiation molecules 4 and 8, CD4 and CD8), and mast cells, and improved cardiac function. Innate immune mediators known to increase myocarditis are decreased by innate PEV treatment including Toll-like receptor (TLR)4 and complement. PEV also significantly reduces perivascular fibrosis and remodeling including interleukin 1 beta (IL-1ß), transforming growth factor-beta 1, matrix metalloproteinase, collagen genes, and mast cell degranulation. PEV given at days 7-9 after infection reduces myocarditis and improves cardiac function. MicroRNA (miR) sequencing reveals that PEV contains miRs that decrease viral replication, TLR4 signaling, and T-cell activation. These data show that EVs from the platelets of healthy individuals can significantly reduce myocarditis and improve cardiac function.

Oligofructose improves small intestinal lipid-sensing mechanisms via alterations to the small intestinal microbiota.

BACKGROUND: Upper small intestinal dietary lipids activate a gut-brain axis regulating energy homeostasis. The prebiotic, oligofructose (OFS) improves body weight and adiposity during metabolic dysregulation but the exact mechanisms remain unknown. This study examines whether alterations to the small intestinal microbiota following OFS treatment improve small intestinal lipid-sensing to regulate food intake in high fat (HF)-fed rats. RESULTS: In rats fed a HF diet for 4 weeks, OFS supplementation decreased food intake and meal size within 2 days, and reduced body weight and adiposity after 6 weeks. Acute (3 day) OFS treatment restored small intestinal lipid-induced satiation during HF-feeding, and was associated with increased small intestinal CD36 expression, portal GLP-1 levels and hindbrain neuronal activation following a small intestinal lipid infusion. Transplant of the small intestinal microbiota from acute OFS treated donors into HF-fed rats also restored lipid-sensing mechanisms to lower food intake. 16S rRNA gene sequencing revealed that both long and short-term OFS altered the small intestinal microbiota, increasing Bifidobacterium relative abundance. Small intestinal administration of Bifidobacterium pseudolongum to HF-fed rats improved small intestinal lipid-sensing to decrease food intake. CONCLUSION: OFS supplementation rapidly modulates the small intestinal gut microbiota, which mediates improvements in small intestinal lipid sensing mechanisms that control food intake to improve energy homeostasis. Video Abstract.

Greenhouse gas assemblages (CO2, CH4 and N2O) in the continental shelf of the Gulf of Cadiz (SW Iberian Peninsula).

This study examines the simultaneous water-atmosphere exchange of carbon dioxide (CO2), methane (CH4) and nitrous oxide (N2O) on the continental shelf of the Gulf of Cadiz, as well as the effect it has in terms of the radiative balance in the atmosphere, between 2014 and 2016. The experimental database consists of new measurements of the spatial and seasonal distribution of CO2 partial pressure (pCO2) and N2O concentration in 2016. pCO2 shows a wide range of variation influenced mainly by seasonal thermal variations (8.0 µatm 0C-1), as well as with the relative intensity of biological activity. There is experimental evidence of a progressive increase of pCO2 over the last 2 decades, with an estimated gradient of 4.2 ± 0.7 µatm y-1. During 2016, the Gulf of Cadiz acted as a slight source of CO2 to the atmosphere, with a mean flux of 0.4 ± 2.2 mmol m-2 d-1. The analysis of concentration variations in the water column shows that nitrification is the main N2O production process in the study area, although in the more coastal zone there are signs of inputs related to continental and sediment contributions, most probably induced by denitrification processes. In 2016, the Gulf of Cadiz acted as a weak sink of atmospheric N2O, with a mean flux of -0.1 ± 0.9 µmol m-2 d-1. From previous studies, performed with a similar methodology, an interannual database (2014-2016) of water-atmosphere fluxes of CO2, CH4 and N2O, normalized to the mean wind speed in the area, has been generated. Considering their respective Global Warming Potential (GWP) a joint greenhouse gasses (GHG) flux, expressed in CO2 equivalents of 0.6 ± 2.0 mmol m-2 d-1, has been estimated, which extended to the area of study indicates an approximate emission of 67.9 Gg CO2 y-1. However, although there is a high uncertainty associated with the spatial, temporal and interannual variations of CO2, CH4 and N2O fluxes in the Gulf of Cadiz, the exchange of greenhouse gasses could be influencing a radiative forcing increase in the atmosphere. When considering the available information on local and global estimates, the uncertainty about the effect of the joint exchange of GHGs to the atmosphere from the coastal seas increases significantly.

Early Dalmatian farmers specialized in sheep husbandry.

The spread of farming in the central and western Mediterranean took place rapidly, linked to the Impressa Ware. The Impressa Ware originated somewhere in the southern Adriatic and spread westwards across the Mediterranean. These early farmers had an economy based on cereal agriculture and caprine husbandry, but there is still little information on how this agropastoral system functioned. This study aims to unravel the farming practices of the early Dalmatian farmers linked to the Impressa culture by using an integrated analysis, combining archaeozoology, palaeoproteomics and stable isotopes, applied to the faunal assemblages of Tinj-Podlivade and Crno Vrilo. The results show: (1) the composition of the flocks was overwhelmingly sheep; (2) sheep exploitation at both sites was similar, focusing on milk and meat; (3) sheep reproduction was concentrated at the beginning of winter, with no reproduction in autumn as in later sites in the western Mediterranean. We conclude that a common animal economy existed at both sites, which could be related to the mobility practiced by these early farming societies throughout the Mediterranean.

KG-Hub-building and exchanging biological knowledge graphs.

MOTIVATION: Knowledge graphs (KGs) are a powerful approach for integrating heterogeneous data and making inferences in biology and many other domains, but a coherent solution for constructing, exchanging, and facilitating the downstream use of KGs is lacking. RESULTS: Here we present KG-Hub, a platform that enables standardized construction, exchange, and reuse of KGs. Features include a simple, modular extract-transform-load pattern for producing graphs compliant with Biolink Model (a high-level data model for standardizing biological data), easy integration of any OBO (Open Biological and Biomedical Ontologies) ontology, cached downloads of upstream data sources, versioned and automatically updated builds with stable URLs, web-browsable storage of KG artifacts on cloud infrastructure, and easy reuse of transformed subgraphs across projects. Current KG-Hub projects span use cases including COVID-19 research, drug repurposing, microbial-environmental interactions, and rare disease research. KG-Hub is equipped with tooling to easily analyze and manipulate KGs. KG-Hub is also tightly integrated with graph machine learning (ML) tools which allow automated graph ML, including node embeddings and training of models for link prediction and node classification. AVAILABILITY AND IMPLEMENTATION: https://kghub.org.

Glycan Node Analysis Detects Varying Glycosaminoglycan Levels in Melanoma-Derived Extracellular Vesicles.

Extracellular vesicles (EVs) play important roles in (patho)physiological processes by mediating cell communication. Although EVs contain glycans and glycosaminoglycans (GAGs), these biomolecules have been overlooked due to technical challenges in comprehensive glycome analysis coupled with EV isolation. Conventional mass spectrometry (MS)-based methods are restricted to the assessment of N-linked glycans. Therefore, methods to comprehensively analyze all glyco-polymer classes on EVs are urgently needed. In this study, tangential flow filtration-based EV isolation was coupled with glycan node analysis (GNA) as an innovative and robust approach to characterize most major glyco-polymer features of EVs. GNA is a molecularly bottom-up gas chromatography-MS technique that provides unique information that is unobtainable with conventional methods. The results indicate that GNA can identify EV-associated glyco-polymers that would remain undetected with conventional MS methods. Specifically, predictions based on GNA identified a GAG (hyaluronan) with varying abundance on EVs from two different melanoma cell lines. Enzyme-linked immunosorbent assays and enzymatic stripping protocols confirmed the differential abundance of EV-associated hyaluronan. These results lay the framework to explore GNA as a tool to assess major glycan classes on EVs, unveiling the EV glycocode and its biological functions.

Comparing Bayesian Variable Selection to Lasso Approaches for Applications in Psychology.

In the current paper, we review existing tools for solving variable selection problems in psychology. Modern regularization methods such as lasso regression have recently been introduced in the field and are incorporated into popular methodologies, such as network analysis. However, several recognized limitations of lasso regularization may limit its suitability for psychological research. In this paper, we compare the properties of lasso approaches used for variable selection to Bayesian variable selection approaches. In particular we highlight advantages of stochastic search variable selection (SSVS), that make it well suited for variable selection applications in psychology. We demonstrate these advantages and contrast SSVS with lasso type penalization in an application to predict depression symptoms in a large sample and an accompanying simulation study. We investigate the effects of sample size, effect size, and patterns of correlation among predictors on rates of correct and false inclusion and bias in the estimates. SSVS as investigated here is reasonably computationally efficient and powerful to detect moderate effects in small sample sizes (or small effects in moderate sample sizes), while protecting against false inclusion and without over-penalizing true effects. We recommend SSVS as a flexible framework that is well-suited for the field, discuss limitations, and suggest directions for future development.

Prophylactic Efficacy of Riluzole against Anxiety- and Depressive-Like Behaviors in Two Rodent Stress Models.

Introduction: Chronic stress-related illnesses such as major depressive disorder and post-traumatic stress disorder share symptomatology, including anxiety, anhedonia, and helplessness. Across disorders, neurotoxic dysregulated glutamate (Glu) signaling may underlie symptom emergence. Current first-line antidepressant drugs, which do not directly target Glu signaling, fail to provide adequate benefit for many patients and are associated with high relapse rates. Riluzole modulates glutamatergic neurotransmission by increasing metabolic cycling and modulating signal transduction. Clinical studies exploring riluzole's efficacy in stress-related disorders have provided varied results. However, the utility of riluzole for treating specific symptom dimensions or as a prophylactic treatment has not been comprehensively assessed. Methods: We investigated whether chronic prophylactic riluzole (∼12-15 mg/kg/day p.o.) could prevent the emergence of behavioral deficits induced by unpredictable chronic mild stress (UCMS) in mice. We assessed (i) anxiety-like behavior using the elevated-plus maze, open-field test, and novelty-suppressed feeding, (ii) mixed anxiety/anhedonia-like behavior in the novelty-induced hypophagia test, and (iii) anhedonia-like behavior using the sucrose consumption test. Z-scoring summarized changes across tests measuring similar dimensions. In a separate learned helplessness (LH) cohort, we investigated whether chronic prophylactic riluzole treatment could block the development of helplessness-like behavior. Results: UCMS induced an elevation in anhedonia-like behavior and overall behavioral emotionality that was blocked by prophylactic riluzole. In the LH cohort, prophylactic riluzole blocked the development of helplessness-like behavior. Discussion/Conclusion: This study supports the utility of riluzole as a prophylactic medication for preventing anhedonia and helplessness symptoms associated with stress-related disorders.