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Mast cell tumours (MCTs) are common malignant neoplasms in dogs, for which prognosis and therapeutic decisions are based on histological features and proliferation markers. Autophagy is a cellular catabolic process responsible for degrading cytoplasmic components to maintain homeostasis, alterations in which are frequently linked to tumour growth and progression. This study was conducted to investigate the occurrence of autophagy in canine MCTs and to verify its value as a prognostic indicator for dogs with the disease. Beclin-1 and LC3B expressions were investigated using immunohistochemistry, and autophagy was ultrastructurally characterised. The autophagic phenomenon was successfully visualised in neoplastic mast cells under transmission electron and immunoelectron microscopy. MCTs from dogs that died due to the disease showed higher positivity for Beclin-1 and dogs with MCTs presenting a LC3B granular immunohistochemical pattern had a significantly shorter post-surgical survival. The occurrence of autophagy is an indicator of poor prognosis. Future studies are needed to elucidate the specific mechanisms and open new opportunities to treatments targeting this cancer cell advantage.

Analysis of clinical and environmental Vibrio cholerae O1 strains obtained during 2008–2015 in Nigeria showed that lineages Afr9 and Afr12 carrying cholera toxin and Vibrio pathogenicity island 1 can be isolated from water. Our findings raise concerns about the role of the environment in maintenance and emergence of cholera outbreaks in Nigeria.

ABSTRACT Introduction and objectives: The optimal treatment of nonculprit angiographic intermediate lesions (diameter stenosis 40%-69%) in patients with ST-segment elevation myocardial infarction (STEMI) is still unknown. Lesions with fractional flow reserve (FFR) ≤ 0.80 are indicative of ischemia and benefit from revascularization. However, lesions with FFR > 0.80 and optical coherence tomography (OCT) findings of vulnerability have been hypothesized to cause adverse events during follow-up. The study aims to compare the efficacy of a preventive treatment with stent implantation plus optimal medical therapy vs optimal medical therapy alone for nonculprit intermediate lesions with FFR > 0.80 and OCT findings of plaque vulnerability in STEMI patients at 4 years of follow-up. Methods: This parallel-group, multicenter, controlled, single-blind, and 1:1 randomized trial will enroll a total of 600 STEMI patients with ≥ 1 intermediate nonculprit lesions with FFR > 0.80 and OCT findings of plaque vulnerability. The primary endpoint is target vessel failure, defined as the composite of cardiac death, target vessel myocardial infarction, or target vessel revascularization. The study will include a parallel registry of patients with FFR > 0.80 but without OCT findings of vulnerability. Vulnerable plaques are defined as lipid-rich fibroathermas with plaque burden ≥ 70% and a thin fibrous cap (≤ 80 μm). Results: The VULNERABLE trial will reveal the role of preventive treatment with stent implantation for nonculprit and functionally nonsignificant vulnerable plaques in STEMI patients. Conclusions: This is the first randomized trial of OCT-guided treatment of vulnerables plaques. Registered at ClinicalTrials.gov (NCT05599061).

Introducción y objetivos: El tratamiento óptimo de las lesiones angiográficas intermedias (diámetro de estenosis 40-69%) no culpables en pacientes con infarto agudo de miocardio con elevación del segmento ST (IAMCEST) está por determinar. La reserva fraccional de flujo (RFF) permite diagnosticar lesiones causantes de isquemia (RFF ≤ 0,80) que se benefician de una revascularización. No obstante, las lesiones con RFF > 0,80 y criterios de vulnerabilidad por tomografía de coherencia óptica (OCT) también se ha hipotetizado que pueden causar eventos adversos en el seguimiento. El objetivo es comparar la eficacia del tratamiento preventivo con implantación de stent más tratamiento médico óptimo de lesiones intermedias no culpables con RFF > 0,80 y características de placa vulnerable frente a solo tratamiento médico óptimo en pacientes con IAMCEST a 4 años de seguimiento. Métodos: Estudio de grupos paralelos, multicéntrico, controlado, aleatorizado 1:1 y simple ciego. Se incluirán 600 pacientes con IAMCEST y al menos una lesión intermedia no culpable que presenten RFF > 0,80 y características de placa vulnerable por OCT. El objetivo primario se define como fallo del vaso diana, compuesto de muerte cardiaca, infarto del vaso diana y necesidad de revascularización del vaso diana. El estudio incluye un registro paralelo para pacientes con RFF > 0,80 sin características de placa vulnerable. Se define placa vulnerable como fibroateromas lipídicos con carga de placa ≥ 70% y capa fibrosa fina (≤ 80 µm). Resultados: El estudio VULNERABLE permitirá conocer el papel del tratamiento preventivo con stent de placas vulnerables no culpables funcionalmente no significativas en pacientes con IAMCEST. Conclusiones: Se trata del primer estudio aleatorizado para el tratamiento de placas vulnerables guiado por OCT. Registrado en ClinicalTrials.gov (NCT05599061).

Abstract Background Despite its proven prognostic value in different contexts, the precise implications of left atrial strain (LAS) assessment throughout different phases of the atrial cycle remain uncertain. A direct correlation between left atrial reservoir strain (LARS) and left ventricular global longitudinal strain (GLS) has been consistently demonstrated in several studies involving patients with various heart diseases. The objective of our study is to identify factors directly associated with LARS, left atrial conduction strain (LACS) and left atrial booster strain (LABS) in patients without cardiovascular (CV) disease. Methods Transthoracic echocardiographic examinations in patients without CV disease were prospectively selected in two tertiary hospitals echocardiography labs for clinical purposes. LAS, maximal and minimal left atrial (LA) volumes and left atrial ejection fraction (LAEF) were measured using the two-dimensional strain analysis package provided by the EchoPAC Plugging workstation (AFI LA). Results A total of 196 cases were included, median age of 54 (45–62) with 85 (43%) being men. The mean left ventricular ejection fraction (LVEF) was 61% ± 5, and the median GLS was − 18% (-17 to -20). Median indexed maximum volume of left atrium (LAVI) was 27 ml/m2 (22–31), and LAEF was 64% (58–70). The mean LARS biplane was 35,1% ± 8. Notably, LARS was greater in the 2-chamber view (36,1% ± 10) compared to the 4-chamber view (34,1% ± 8 p

Abstract During COVID-19 pandemic, international pharmaceutical companies put effort to build global manufacturing networks for vaccines. Soberana Plus vaccine, a recombinant protein based vaccine (RBD dimer), with the trade name of PastoCovac Plus in Iran, is based on a protein subunit platform in Cuba and completed preclinical and toxicological assessments. This study aimed at presenting the steps of vaccine technology transfer from Cuba to Iran. This study provides the first practical comparability results in Iran to ensure the quality, safety and efficacy of a protein subunit vaccine against COVID-19 after a successful technology transfer from Cuba. PastoCovac Plus was transferred to Iran at the formulation stage. The assessment of the active ingredient pharmaceutical (API) was achieved through physicochemical and clinical data collection and tests to assure if there was any adverse impact on the vaccination results. In order to assess the quality of the vaccine product after technology transfer, we sought different properties including regulatory features, physicochemical quality, vaccine potency and stability as well as its immunogenicity and safety. Following the evaluation of the clinical quality attributes (CQAs) based on the standard protocols, the results showed that the two vaccines are highly similar and comparable, with no considerable effect on safety or efficacy profiles. The CQAs were all in the acceptance limits in terms of safety and efficacy as well as clinical evaluation results. The immunogenicity evaluation also confirmed no significant differences between the vaccines regarding reinfection (P = 0.199) or vaccine breakthrough (P = 0.176). Furthermore, the level of anti-spike and neutralizing antibodies in the both vaccine groups was not significantly different indicating the equality of performance between the two vaccines. According to the results of the quality and clinical assessment of this study, we achieved an acceptable quality attributes and acceptant limits in terms of safety and efficacy of the vaccines pre and post technology transfer.

Abstract Vitamin D (vitD) deficiency is frequently observed in patients with pulmonary arterial hypertension (PAH) and, in these patients, low levels of vitD correlate with worse prognosis. The aim of this study was to examine the expression and the antiproliferative role of vitD receptor (VDR) and its signalling pathway in the human pulmonary vasculature. VDR presence and expression was analyzed in lungs, pulmonary artery smooth muscle cells (PASMC) and endothelial cells (PAEC) from controls and PAH-patients. VDR expression and VDR-target genes were examined in PASMC treated with calcitriol. The antiproliferative effect of 48 h-calcitriol was studied in PASMC by MTT and BrdU assays. VDR is expressed in PASMC. It is downregulated in lungs and in PASMC, but not in PAEC, from PAH-patients compared to non-hypertensive controls. Calcitriol strongly upregulated VDR expression in PASMC and the VDR target genes KCNK3 (encoding TASK1), BIRC5 (encoding survivin) and BMP4. Calcitriol produced an antiproliferative effect which was diminished by silencing or by pharmacological inhibition of survivin or BMPR2, but not of TASK1. In conclusion, the expression of VDR is low in PAH-patients and can be rescued by calcitriol. VDR exerts an antiproliferative effect in PASMC by modulating survivin and the BMP signalling pathway.

Abstract Recessive dystrophic epidermolysis bullosa (RDEB) is a rare genetic disease caused by loss of function mutations in the gene coding for collagen VII (C7) due to deficient or absent C7 expression. This disrupts structural and functional skin architecture, leading to blistering, chronic wounds, inflammation, important systemic symptoms affecting the mouth, gastrointestinal tract, cornea, and kidney function, and an increased skin cancer risk. RDEB patients have an extremely poor quality of life and often die at an early age. A frequent class of mutations in RDEB is premature termination codons (PTC), which appear in homozygosity or compound heterozygosity with other mutations. RDEB has no cure and current therapies are mostly palliative. Using patient-derived keratinocytes and a library of 8273 small molecules and 20,160 microbial extracts evaluated in a phenotypic screening interrogating C7 levels, we identified three active chemical series. Two of these series had PTC readthrough activity, and one upregulated C7 mRNA, showing synergistic activity when combined with the reference readthrough molecule gentamicin. These compounds represent novel potential small molecule-based systemic strategies that could complement topical-based treatments for RDEB.

Dielectric resonator antennas have been demonstrated to be an efficient radiator, especially with the possibility of fabricating it at low cost based on 3-D printing technologies. However, they have two main limitations which are: their relatively small gain (about 5dBi) and narrow bandwidth. To enhance the gain of DRA, higher-order mode excitation can be utilized; however, typically this has a limit of a few dB increments besides its negative effects on the bandwidth. This study employs a cavity-backed slot to provide an appropriate feeding method for a cylindrical dielectric resonator antenna (CDRA). This design effectively facilitates the excitation of higher-order modes, resulting in a significant gain of up to 15 dBi, which is essential for many wireless systems that are unable to support larger aperture sizes through the standard use of arrays. Additionally, two modes are excited to keep a relatively broadband of about 15 %. The proposed design consists of a cylindrical dielectric placed on top of a cavity-backed slot that is excited by a coaxial probe soldered to the top patch of the cavity. With this feeding, a good matching is achieved for different dielectric resonator heights, hence, the gain can be adjusted easily without the need of reoptimizing the antenna or the feed structures. The design process is explained in addition to performing a sensitivity analysis of fabrication tolerances which confirms that the 3-D printer provides enough accuracy with a negligible effect on the antenna’s performance. Then a prototype with a medium length is fabricated and measured to provide high realized gain and impedance bandwidth of 11 dBi and 14.5 %, respectively. The measured data demonstrate the good performance of the antenna with great matching compared to the simulated ones. Furthermore, the antenna presents a good performance in terms of sidelobes and polarization. This proposed design outperforms other DRA designs based on higher-order modes.

Purpose: Our objective was to synthesize and determine whether there are sex differences in physical function following exercise interventions in older adults. Materials and Methods: A systematic search was conducted in four databases from inception to July 8th, 2023 searching for prospective trials that conducted exercise interventions in older adults and results for physical function were reported by sex. Pooled standardized mean differences (SMDs) with their 95% confidence intervals (CIs) were estimated using a randomeffects method. The Sidik-Jonkman estimator was used to calculate the variance of heterogeneity (I2). Results: A total of 19 studies involving 20,133 older adults (mean age ≥60 years, 33.7% female) were included. After exercise interventions, males reported significantly greater pre-post changes compared to females for upper body strength (SMD=- 0.40, 95% CI: -0.71 to -0.09; I2=75.6%; n=8), lower body strength (SMD=-0.32, 95% CI: -0.55 to -0.10; I2=52.0%; n=11), and cardiorespiratory fitness (SMD=-0.29, 95% CI: -0.48 to -0.10; I2=89.1%; n=12). Conversely, the pooled SMDs showed a significant effect favoring females for motor fitness (SMD=0.21, 95% CI: 0.03 to 0.39; I2=0%; n=7). Limited and inconsistent results were observed for flexibility. Conclusions: Our study suggests the existence of sex-related differences on physical function after an exercise intervention in the older population.

A mandioca apresenta ampla diversidade genética, podendo ser analisada por meio de marcadores moleculares. Dentre os disponíveis, estão os ISSR que são marcadores dominantes, universais e com alto índice de polimorfismo. Diante disso, esse estudo tem como objetivo avaliar a diversidade genética entre etnovariedades de mandioca cultivadas em assentamentos rurais no norte do estado de Mato Grosso, por meio de marcadores moleculares ISSR. Foram coletadas folhas de 30 etnovariedades cultivadas em três assentamentos rurais (São Paulo, Jacaminho e São Pedro) localizados em três municípios (Carlinda, Alta Floresta e Paranaíta) no norte do estado de Mato Grosso, Brazil. Para a extração do DNA total, seguiu-se o método CTAB. As amplificações foram realizadas via PCR utilizando 15 primers ISSR. Os primers ISSR amplificaram 190 fragmentos, dos quais 76,32% foram polimórficos. Os métodos de agrupamento formaram cinco grupos, demonstrando que há diversidade genética entre as etnovariedades de mandioca, com destaque para JAC09 (Cacau talo roxo) e SPA04 (Mandioca pão) como as mais divergentes dentro do acervo. Os assentamentos rurais são importantes locais para a conservação on farm da espécie.

Abstract Background Sarcopenia and low areal bone mineral density (aBMD) are prevalent musculoskeletal complications after paediatric cancer treatment. However, their relationship has not been examined in young paediatric cancers survivors. This study aimed to evaluate aBMD differences according to sarcopenia status and the risk of low aBMD Z‐score in young paediatric cancer survivors with sarcopenia confirmed/probable. Methods This cross‐sectional study included 116 paediatric cancer survivors (12.1 ± 3.3 years old; 42.2% female). Handgrip strength was used to assessed muscle strength. Dual‐energy X‐ray absorptiometry estimated aBMD (g/cm2) and appendicular lean mass index (ALMI, kg/m2). ‘No sarcopenia’ was defined when muscle strength was >decile 2. ‘Sarcopenia probable’ was defined when muscle strength was ≤ decile 2 and ALMI Z‐score was > −1.5 standard deviation (SD). ‘Sarcopenia confirmed’ was defined when muscle strength was ≤ decile 2 and ALMI Z‐score ≤ −1.5 SD. Analysis of covariance and logistic regression, adjusted for time from treatment completion, radiotherapy exposure, calcium intake, and physical activity, was used to evaluate aBMD and estimate the odds ratios (ORs) of low aBMD (aBMD Z‐score < −1.0). Results Survivors with sarcopenia confirmed had significantly lower aBMD than those without sarcopenia at total body (−1.2 [95% CI: −1.5 to −0.8] vs. 0.2 [−0.2 to 0.6], P

Abstract Background The effects of post‐coronavirus disease 2019 (COVID‐19) syndrome on the cardiorespiratory and muscular fitness in older people are of utmost relevance. This study aimed to evaluate the effects of a 12‐week telerehabilitation programme on cardiorespiratory and muscular fitness and body composition in older patients with post‐COVID‐19 syndrome. Methods One hundred twenty older patients with post‐COVID‐19 syndrome were randomly assigned to one of two groups: patients who carried out the telerehabilitation programme (n = 60; age: 65.0 ± 5.2; female: 14.2%) and a control group (n = 60; age: 64.3 ± 5.0; female: 24.5%). An incremental cardiopulmonary exercise testing, isokinetic strength test, and bioelectrical impedance analysis were performed to compare cardiorespiratory and muscle strength responses and body composition between telerehabilitation and control groups. Results A significant increase in the cardiopulmonary exercise testing duration was found in the telerehabilitation group compared to the control group (mean difference = 88.9 s, P = 0.001). Peak oxygen uptake increased in the telerehabilitation group (mean difference = 3.0 mL·kg−1·min−1, P

Abstract Background Sarcopenia, the gradual and generalized loss of muscle mass and function with ageing, is one of the major health problems in older adults, given its high prevalence and substantial socioeconomic implications. Despite the extensive efforts to reach consensus on definition and diagnostic tests and cut‐offs for sarcopenia, there is an urgent and unmet need for non‐invasive, specific and sensitive biomarkers for the disease. Extracellular vesicles (EVs) are present in different biofluids including plasma, whose cargo reflects cellular physiology. This work analysed EV proteome in sarcopenia and robust patients in the search for differentially contained proteins that can be used to diagnose the disease. Methods Plasma small EVs (sEVs) from a total of 29 robust controls (aged 73.4 ± 5.6 years; 11 men and 18 women) and 49 sarcopenic patients (aged 82.3 ± 5.4 years; 15 men and 34 women) aged 65 years and older were isolated and their cargo was analysed by proteomics. Proteins whose concentration in sEVs was different between sarcopenic and robust patients were further validated using ELISA. The concentration of these candidates was correlated to the EWGSOP2 sarcopenia tests for low muscle strength and low physical performance, and receiver operating characteristic (ROC) curve analyses were carried out to evaluate their diagnostic power, sensitivity and specificity. Results Proteomic analysis identified 157 sEVs proteins in both sarcopenic and robust samples. Among them, 48 proteins had never been reported in the ExoCarta nor Vesiclepedia databases. Statistical analysis revealed eight proteins whose concentration was significantly different between groups: PF4 (log2 FC = 4.806), OIT3 (log2 FC = −1.161), MMRN1 (log2 FC = −1.982), MASP1 (log2 FC = −0.627), C1R (log2 FC = 1.830), SVEP1 (log2 FC = 1.295), VCAN (FC = 0.937) and SPTB (log2 FC = 1.243). Among them, platelet factor 4 (PF4) showed the lowest concentration while Complement C1r subcomponent (C1R) increased the most in sarcopenic patients, being these results confirmed by ELISA (P = 1.07E‐09 and P = 0.001287, respectively). The concentrations of candidate proteins significantly correlated with EWGSOP2 tests currently used. ROC curve analysis showed an area under the curve of 0.8921 and 0.7476 for PF4 and C1R, respectively. Choosing the optimal for PF4, 80% sensitivity and 85.71% specificity was reached while the optimal cut‐off value of C1R would allow sarcopenia diagnosis with 75% sensitivity and 66.67% specificity. Conclusions Our results support the determination of EV PF4 and C1R as plasma diagnostic biomarkers in sarcopenia and open the door to investigate the role of the content of these vesicles in the pathogeny of the disease.

La situación de despoblación que atraviesa el medio rural en España desde hace más de medio siglo ha conllevado al progresivo abandono y pérdida de la arquitectura tradicional en entornos agroforestales. En el contexto actual, donde los criterios de sostenibilidad establecen un paradigma, el rescate y reutilización de estas construcciones tradicionales (masías, alquerías, ventas, corrales, etc.) representa en sí una actuación sostenible. Implementar soluciones arquitectónicas de bajo impacto ambiental y económicamente viables que contribuyan a la revitalización del patrimonio rural, es una muy buena oportunidad para desarrollar y aplicar nuevas metodologías y materiales en procesos y sistemas de construcción sostenible, tal como marca el Pacto Verde Europeo y, concretamente, con la Estrategia Europea de Bioeconomía y la Directiva de Eficiencia Energética. Bajo estos principios, en este trabajo se propone una metodología de intervención que permite la integración de la arquitectura preexistente con elementos prefabricados, constituidos mediante madera y corcho como materiales ecológicos. Como ejemplo de aplicación de esta metodología, se expone la intervención para la rehabilitación de un edificio rural en ruinas con el fin de ser utilizado con uso público, concretamente como centro de interpretación de un yacimiento arqueológico íbero.

Abstract Background Discrimination may further impede access to medical care for individuals in socially disadvantaged positions. Sociodemographic information and perceived discrimination intersect and define multiple contexts or strata that condition the risk of refraining from seeking physician’s care. By applying analysis of individual heterogeneity and discriminatory accuracy (AIHDA) we aimed to improve the mapping of risk by considering both strata average risk differences and the accuracy of such strata risks for distinguishing between individuals who did or did not refrain from seeking physician’s care. Methods We analysed nine annual National Public Health Surveys (2004, 2007–2014) in Sweden including 73,815 participants. We investigated the risk of refraining from seeking physician’s care across 64 intersectional strata defined by sex, education, age, country of birth, and perceived discrimination. We calculated strata-specific prevalences and prevalence ratios (PR) with 95% confidence intervals (CI), and the area under the receiver operating characteristic curve (AUC) to evaluate the discriminatory accuracy (DA). Results Discriminated foreign-born women aged 35–49 with a low educational level show a six times higher risk (PR = 6.07, 95% CI 5.05–7.30) than non-discriminated native men with a high educational level aged 35–49. However, the DA of the intersectional strata was small (AUC = 0.64). Overall, discrimination increased the absolute risk of refraining from seeking physician’s care, over and above age, sex, and educational level. Conclusions AIHDA disclosed complex intersectional inequalities in the average risk of refraining from seeking physician’s care. This risk was rather high in some strata, which is relevant from an individual perspective. However, from a population perspective, the low DA of the intersectional strata suggests that potential interventions to reduce such inequalities should be universal but tailored to the specific contextual characteristics of the strata. Discrimination impairs access to healthcare.

Abstract The last decade has seen significant improvements in our understanding of skyrmions current induced dynamics, along with their room temperature stabilization, however, the impact of local material inhomogeneities still remains an issue that impedes reaching the regime of steady state motion of these spin textures. Here, we study the spin-torque driven motion of skyrmions in synthetic ferrimagnetic multilayers with the aim of achieving high mobility and reduced skyrmion Hall effect. We consider Pt|Co|Tb multilayers of various thicknesses with antiferromagnetic coupling between the Co and Tb magnetization. The increase of Tb thickness in the multilayers reduces the total magnetic moment and increases the spin-orbit torques allowing to reach velocities up to 400 ms−1 for skyrmions with diameters of about 160 nm. We demonstrate that due to reduced skyrmion Hall effect combined with the edge repulsion of the magnetic track, the skyrmions move along the track without any transverse deflection. Further, by comparing the field-induced domain wall motion and current-induced skyrmion motion, we demonstrate that the skyrmions at the largest current densities present all the characteristics of a dynamical flow regime.

Abstract Bioactive metabolites play a crucial role in shaping interactions among diverse organisms. In this study, we identified cyclo(Pro-Tyr), a metabolite produced by Bacillus velezensis, as a potent inhibitor of Botrytis cinerea and Caenorhabditis elegans, two potential cohabitant eukaryotic organisms. Based on our investigation, cyclo(Pro-Tyr) disrupts plasma membrane polarization, induces oxidative stress and increases membrane fluidity, which compromises fungal membrane integrity. These cytological and physiological changes induced by cyclo(Pro-Tyr) may be triggered by the destabilization of membrane microdomains containing the [H+]ATPase Pma1. In response to cyclo(Pro-Tyr) stress, fungal cells activate a transcriptomic and metabolomic response, which primarily involves lipid metabolism and Reactive Oxygen Species (ROS) detoxification, to mitigate membrane damage. This similar response occurs in the nematode C. elegans, indicating that cyclo(Pro-Tyr) targets eukaryotic cellular membranes.

Abstract Background Mexico reports low follow-up completion rates among women with abnormal cervical cancer screenings. This study aimed to identify barriers and facilitators to follow-up adherence among women with human papillomavirus (HPV) infection and premalignant cervical lesions in Mexico. Methods A mixed-methods study was conducted from February to April 2019. Participants included women undergoing follow-up care for high-risk human papillomavirus (HR-HPV) and premalignant lesions, along with health personnel from the Women’s Healthcare Center (CAPASAM) in Mexico. Quantitative data were obtained from the Women’s Cancer Information System and through a questionnaire about factors affecting follow-up adherence. Additionally, the health personnel involved completed a compliance checklist regarding care regulations. Descriptive statistics were used for analysis. Qualitative data were collected via semi-structured interviews with both groups, followed by a content analysis based on identified categories. The Hazard Analysis and Critical Control Point System confirmed care process risks. Proposals to enhance the Early Detection Program for Prevention and Control of Cervical Cancer were collected from a CAPASAM health personnel nominal group. Results Identified barriers to follow-up included low income among CAPASAM users, family provider roles limiting time for appointments, long waits for testing and results delivery, distant facilities, insufficient service hour communication, inadequate health personnel training, and a lack of systematic counseling. Hesitation toward follow-up was also linked to shame, apprehension, uncertainty, test aversion, fear of positive results, and limited cervical cancer and screening knowledge. Patriarchal attitudes of partners and limited access to the now-discontinued PROSPERA government program further discouraged follow-up. Facilitators comprised respectful treatment by CAPASAM staff, no-cost services, health campaigns, and positive user attitudes. Conclusions The study found more barriers than facilitators to follow-up adherence, highlighting the need for strategies to bolster the Early Detection Program. Future strategies must address the comprehensive array of factors and incorporate stakeholder perspectives.

Introduction: Chiari Malformation Type I (CM-I) involves the descent of the cerebellar tonsils 5 mm through the foramen magnum. This case report discusses a patient with dysphagia and glossopharyngeal neuralgia as unusual symptoms of CM-I. Case Presentation: A 59-year-old Afro-Colombian housewife presented with a clinical picture that began three years ago with dysphagia for solids and liquids, coughing when swallowing, recurrent cervical pain, and xerostomia. A neurological examination revealed deviation of the uvula to the right and absence of the gag reflex. A cerebral nuclear magnetic resonance (NMR) was performed, showing the descent of the cerebellar tonsils through the foramen magnum, compressing the medulla oblongata. CM-I was diagnosed, and the anomaly was corrected. The patient reported complete improvement of dysphagia and associated symptoms. Conclusions: CM-I poses a diagnostic challenge when presenting with dysphagia and glossopharyngeal neuralgia; however, timely diagnosis defines its proper management and prognosis.

Abstract The ongoing increase in wild boar populations across Europe has fostered human–wildlife conflicts, including the transmission of emerging pathogens with zoonotic importance. Blastocystis is a ubiquitous, faecal-oral transmitted protist that can cause gastrointestinal illnesses and is observed in humans and animals worldwide. The role of wildlife in the epidemiology of Blastocystis is insufficiently understood. Thus, we investigated the occurrence and subtype diversity of Blastocystis in free-ranging wild boars from the Iberian Peninsula using conventional PCR and next-generation amplicon sequencing of a fragment of the ssu RNA gene. A total of 459 wild boar faecal samples were collected across Spain (n = 360) and Portugal (n = 99) between 2014 and 2021. Blastocystis was present in 15.3% (70/459; 95% CI 12.1–18.9) of the wild boars analysed, and its occurrence was significantly higher in Portugal (34.3%, 34/99; 95% CI 25.1–44.6) than in Spain (10.0%, 36/360; 95% CI 7.1–13.6). Seven Blastocystis subtypes (ST5, ST10b, ST13–ST15, ST24b, and ST43) were detected among the surveyed wild boar populations, with greater variability detected in Portuguese samples. ST5 was identified in all the Blastocystis-positive animals, whereas 14.3% of them harboured ST mixed colonisations. Our results demonstrate that Blastocystis ST5 is particularly adapted to infect wild boars. The additional identification of zoonotic STs reinforces the role of wild boars as spreaders of zoonotic infections with public health significance.

Abstract Drought is one of the most damaging hydroclimatic hazards, impacting environmental systems and socioeconomic sectors. Therefore, understanding the physical mechanisms that cause drought events is of critical importance. Here we investigate the influence of oceanic and continental moisture deficits on global meteorological drought events in recent decades, utilizing a Lagrangian dispersion model to track the origin of precipitation deficits leading to droughts. Additionally, meteorological drought events between 1980 and 2018 were segmented based on a three-dimension algorithm considering spatial extent, duration, and magnitude of drought events. Severe meteorological drought events exhibit mixed contribution of precipitation deficits from both continental and oceanic sources. This highlights the importance of considering both types of deficits in understanding severe meteorological droughts. Comparative analysis across time periods shows a consistent pattern in the dominant mixed contribution of precipitation deficits. There is no relevant decadal change in the mixed contributions of these deficits, which implies stability in the prevalence of oceanic and continental sources driving extreme drought events. These findings offer valuable insights into the factors shaping meteorological drought evolution.

With the advent of modern Medicine, the connections between emotions and medical conditions have primarily been described through observational studies, where conclusions are drawn from correlations of observations rather than experimental research. Psychoanalytical theory has often been used to explain many common illnesses. This approach remains prevalent today. Interestingly, despite the wealth of information now available on the influence of emotions on health, the current divide between neurology and psychiatry, as well as the separation between mental health services and primary care, combined with the time constraints and physicians’ workload, have led to a fragmented approach to many disorders. In these cases, psychological and emotional factors play an important role but are often inadequately addressed. The objective of this paper is to analyse the existing evidence on the relationship between anger and health through a narrative review. The evidence and data presented point to the need for analytical studies based on scientific methodology to explore the relationship between anger and health, and particularly to adopt an integral health approach taking into account social determinants and the role of empathy among the healthcare professionals and clinical and social care. The prevention and treatment of problems related to the high prevalence and intensity of anger are particularly relevant, given the potential negative impact this emotion can have on patients’ physical and mental health, as well as their social adjustment and relationships.

Abstract Background Type 2 diabetes mellitus (T2DM) is a major risk factor for heart failure with preserved ejection fraction and cardiac arrhythmias. Precursors of these complications, such as diabetic cardiomyopathy, remain incompletely understood and underdiagnosed. Detection of early signs of cardiac deterioration in T2DM patients is critical for prevention. Our goal is to quantify T2DM-driven abnormalities in ECG and cardiac imaging biomarkers leading to cardiovascular disease. Methods We quantified ECG and cardiac magnetic resonance imaging biomarkers in two matched cohorts of 1781 UK Biobank participants, with and without T2DM, and no diagnosed cardiovascular disease at the time of assessment. We performed a pair-matched cross-sectional study to compare cardiac biomarkers in both cohorts, and examined the association between T2DM and these biomarkers. We built multivariate multiple linear regression models sequentially adjusted for socio-demographic, lifestyle, and clinical covariates. Results Participants with T2DM had a higher resting heart rate (66 vs. 61 beats per minute, p

Abstract Hepatocytes-like cells (HLC) derived from human induced pluripotent stem cells show great promise for cell-based liver therapies and disease modelling. However, their application is currently hindered by the low production yields of existing protocols. We aim to develop a bioprocess able to generate high numbers of HLC. We used stirred-tank bioreactors with a rational control of dissolved oxygen concentration (DO) for the optimization of HLC production as 3D aggregates. We evaluated the impact of controlling DO at physiological levels (4%O2) during hepatic progenitors’ stage on cell proliferation and differentiation efficiency. Whole transcriptome analysis and biochemical assays were performed to provide a detailed characterization of HLC quality attributes. When DO was controlled at 4%O2 during the hepatic progenitors’ stage, cells presented an upregulation of genes associated with hypoxia-inducible factor pathway and a downregulation of oxidative stress genes. This condition promoted higher HLC production (maximum cell concentration: 2 × 106 cell/mL) and improved differentiation efficiencies (80% Albumin-positive cells) when compared to the bioreactor operated under atmospheric oxygen levels (21%O2, 0.6 × 106 cell/mL, 43% Albumin positive cells). These HLC exhibited functional characteristics of hepatocytes: capacity to metabolize drugs, ability to synthesize hepatic metabolites, and inducible cytochrome P450 activity. Bioprocess robustness was confirmed with HLC derived from different donors, including a primary hyperoxaluria type 1 (PH1) patient. The generated PH1.HLC showed metabolic features of PH1 disease with higher secretion of oxalate compared with HLC generated from healthy individuals. This work reports a reproducible bioprocess, that shows the importance of controlling DO at physiological levels to increase HLC production, and the HLC capability to display PH1 disease features.

Abstract Fungal pathogens must exhibit strong nutritional plasticity, effectively sensing and utilizing diverse nutrients to support virulence. How the signals generated by nutritional sensing are efficiently translated to the morphogenetic machinery for optimal growth and support of virulence remains incompletely understood. Here, we show that the conserved morphogenesis-related kinase, CotA, imparts isoform-specific control over Aspergillus fumigatus invasive growth in host-mimicking environments and during infection. CotA-mediated invasive growth is responsive to exogenous carbon source quality, with only preferred carbon sources supporting hyphal morphogenesis in a mutant lacking one of two identified protein isoforms. Strikingly, we find that the CotA protein does not regulate, nor is cotA gene expression regulated by, the carbon catabolite repression system. Instead, we show that CotA partially mediates invasive growth in specific carbon sources and virulence through the conserved downstream effector and translational repressor, SsdA. Therefore, A. fumigatus CotA accomplishes its conserved morphogenetic functions to drive pathogenic growth by translating host-relevant carbon source quality signals into morphogenetic outputs for efficient tissue invasive growth.

Abstract Background Connecting the composition and function of industrial microbiomes is a major aspiration in microbial biotechnology. Here, we address this question in wine fermentation, a model system where the diversity and functioning of fermenting yeast species are determinant of the flavor and quality of the resulting wines. Results First, we surveyed yeast communities associated with grape musts collected across wine appellations, revealing the importance of environmental (i.e., biogeography) and anthropic factors (i.e., farming system) in shaping community composition and structure. Then, we assayed the fermenting yeast communities in synthetic grape must under common winemaking conditions. The dominating yeast species defines the fermentation performance and metabolite profile of the resulting wines, and it is determined by the initial fungal community composition rather than the imposed fermentation conditions. Yeast dominance also had a more pronounced impact on wine meta-transcriptome than fermentation conditions. We unveiled yeast-specific transcriptomic profiles, leveraging different molecular functioning strategies in wine fermentation environments. We further studied the orthologs responsible for metabolite production, revealing modules associated with the dominance of specific yeast species. This emphasizes the unique contributions of yeast species to wine flavor, here summarized in an array of orthologs that defines the individual contribution of yeast species to wine ecosystem functioning. Conclusions Our study bridges the gap between yeast community composition and wine metabolite production, providing insights to harness diverse yeast functionalities with the final aim to producing tailored high-quality wines. Video Abstract

Abstract The Euromediterranean area is a key region in which the link between atmospheric moisture transport and hydrometeorological extremes concerns. Atmospheric rivers, the main moisture transport mechanism affecting the region, play a notable role in extreme precipitation there. Moreover, moisture transport deficits from two of the major oceanic moisture sources of the planet, the North Atlantic Ocean and the Mediterranean Sea, are strongly related to drought occurrence in that region. Here, we examine the projected changes in these relationships with global warming, under a high-emission scenario (shared socioeconomic pathway 5–8.5). Here we show that, for the mid-21st century, a moderate increase in the influence of moisture transport on winter precipitation maxima is projected, in line with its increasing concurrence with atmospheric rivers. A stronger increase is estimated for the relationship between moisture transport deficits and drought occurrence, for which probabilities between two and three times greater than those observed in the present climate are obtained for the mid- and end-21st century. This highlights the increasing importance of moisture transport from the ocean in future droughts in the region, especially in the context of reduced local moisture inputs from terrestrial evaporation as a consequence of drier soil.

El síndrome de Down (SD) es un trastorno genético que conlleva una serie de problemas de salud, entre ellos, una reducción de la capacidad cardiorrespiratoria. En el caso de las personas con SD, resulta complicado conseguir una evaluación precisa de la composición corporal, debido a su singular morfología. Sin embargo, se trata de un componente crucial para la detección precoz de la obesidad y para el diseño de intervenciones específicas sobre los hábitos. Participaron en el estudio cuatro corredores varones con SD, que se sometieron a mediciones antropométricas y al análisis vectorial de impedancia bioeléctrica (modalidades clásica y específica) antes y después de completar la carrera de 14 kilómetros. Se emplearon varias ecuaciones para estimar la composición corporal. Asimismo, se hizo un análisis del somatotipo y se compararon los cambios bioeléctricos que provocó la carrera. Se reveló una variabilidad considerable en la composición corporal y el rendimiento en carrera de las personas con SD. Las diversas ecuaciones para estimar la masa grasa arrojaron resultados variables (del 4.2 al 33.3 %). En particular, se observó un patrón único en cada participante en cuanto a la cantidad de líquidos. El Participante 1 destacó con un ángulo de fase marcadamente alto (9.8°), mientras que los demás obtuvieron valores medios inferiores (4.5-6.3°). El análisis del vector de impedancia bioeléctrica indicó una pérdida normal de líquidos durante la carrera (T2 = 92.2; p < .0001). Resultó sorprendente que el Participante 1, el cual consiguió el menor tiempo de carrera, experimentase la pérdida de líquidos más significativa, pero mostrase una mayor retención de agua intracelular. Este estudio subraya la importancia de diseñar métodos de evaluación de la composición corporal adaptados a las personas con SD. El diseño de herramientas de evaluación precisas contribuirá a mejorar el bienestar de esta población en su búsqueda de estilos de vida activos. Estas conclusiones arrojan luz sobre la compleja relación entre composición corporal, hidratación y rendimiento en personas con SD.

Background High levels of physical conditioning are associated with improvements in cognitive performance. In this sense, electroencephalographic (ECG) correlates are used to investigate the enhancing role of physical exercise on executive functions. Oscillations in the β frequency range are proposed to be evident during sensorimotor activity.

Introduction: The six-minute walk test is a stress test that provides information about exercise tolerance in chronic diseases. The aim of the study was to develop reference equations with normal values for the test in healthy children aged 6–12 years in our paediatric reference population. Patients and methods: The six-minute walk test was carried out in a sample of 236 healthy children, analyzing pre- and post-test variables, and we developed reference equations selecting variables that turned out to be significant (P

Background and Aim: The Wild Animal Screening Center in Espírito Santo State (CETAS-ES), Brazil, treats wildlife from trafficking and illegal trade, accidents, captivity, and rescue from out of their habitat. The present study described the trends in wildlife admission to the CETAS-ES over the past 10 years and discussed the impact of animal exploitation. Materials and Methods: This descriptive study used a database provided by the CETAS-ES with data on animals admitted between 2011 and 2021, including admission year, origin, place of captivity, taxonomic category, sex, life stage, and health status. Results: Over 10 years, 23,176 animals were admitted, with an annual average of 2,106 admissions. Seizing was the most common origin (60.39%), followed by rescues/collections (22.60%) and voluntary delivery (11.7%), whereas 5.3% had unidentified origins. Birds were the most frequently admitted animals (80.6%) and were predominant among those seized (97.5%), rescued/collected (46.7%), and voluntarily delivered (73.2%). Mammals represented 45.0% of rescues/collections and reptiles represented 19.0% of voluntary deliveries. Conclusion: The admissions reveal a vulnerable scenario for wildlife in the Brazilian Atlantic Rainforest of Espírito Santo State, mainly affecting birds. Seizing was a common occurrence over the decade, reinforcing the necessity of actions to prevent wildlife trafficking and illegal trade.

Abstract Background It is a challenge for the ambulance service to identify which patients to convey to the emergency department (ED). Ideally this would be the patients with serious conditions requiring further care in the ED. However, patients presenting with non-specific chief complaints are difficult to prioritize and typically have normal or near normal vital signs despite up to one third having underlying serious conditions. The proportion of patients with serious conditions among non-conveyed patients with non-specific chief complaints (NSC) as assessed by ambulance clinicians is not known. Therefore, the primary aim was to study the proportion of serious conditions among conveyed and non-conveyed patients presenting to the ambulance service with NSCs. The secondary aim was to study the mortality rate among patients with NSCs in relation to conveyance and serious and nonserious conditions. Method A retrospective cohort study of patients ≥ 18 years of age presenting with NSCs to the ambulance service in Stockholm Region between January 1st, 2013 and December 31st, 2013. Patients were identified via the ambulance service electronic health record and followed via records from the the National Patient Register and Causes of Death Registry at Sweden’s National Board for Health and Welfare. Descriptive statistics as well as regression analyses were used. Results A total of 4744 patients were included with a median age of 76 years. A serious condition was present in 1398 (29.5%) of the patients. After index assessment by the ambulance service, 3780 (79.7%) were conveyed of which 1334 (35.3%) had serious conditions, compared to 964 (20.3%) who were non-conveyed of which 64 (6.6%) had serious conditions. 30-day mortality was 372 (9.8%) in the conveyance group compared to 32 (3.3%) in the non-conveyance group. If serious conditions were present, the mortality rates were 269 (20.2%) in the conveyance group compared to 11 (17.2%) in the non-conveyance group. Conclusion The results show that serious conditions were more than five times more common among conveyed as compared to non-conveyed patients. Mortality rates were three times higher in the conveyance group as compared to the non-conveyance group. Our results suggest that the ambulance personnel play an important role in identifying patients with serious conditions, hence, likely to be in need of treatment in the ED. Trial registration N/A

Abstract Variants in GBA1 result in dysregulated sphingolipids. We investigated five CSF d18:1 sphingolipid species in a longitudinal multicenter cohort comprising people with Parkinson’s Disease and Dementia with Lewy bodies with and without GBA1 variants and healthy controls. We found no increase of sphingolipid species in heterozygous GBA1 variant participants and no effect on development of cognitive impairment. Thus, CSF d18:1 sphingolipids are not suitable as state markers in Parkinson’s Disease.

Abstract Cognitive impairment and symptoms of psychiatric disorders have been reported frequently as features of post-acute sequelae of SARS-CoV-2 infection. This study aims to investigate subjective memory complaints in COVID-19 survivors and determine if these are more strongly associated with objective cognitive impairment related to sequelae of SARS-CoV-2 infection or with symptoms of psychiatric conditions. A total of 608 COVID-19 survivors were evaluated in-person 6–11 months after hospitalization, with 377 patients assigned to a “no subjective memory complaint (SMC)” group and 231 patients assigned to an SMC group based on their Memory Complaint Scale scores. Follow-up evaluations included an objective cognitive battery and scale-based assessments of anxiety, depression, and post-traumatic stress symptoms. We found the perception of memory impairment in COVID-19 survivors to be more strongly associated to core symptoms of psychiatric conditions rather than to primary objective cognitive impairment. Univariate analysis indicated significant differences between the “no SMC” and SMC groups, both for the psychiatric symptom evaluations and for the cognitive evaluations (p

Abstract Juvenile‐onset Huntington's disease (HD) is a rare subset of HD with symptom‐onset before the age of 18. In contrast to the adult population, children present early‐on with behavioral, psychiatric, and cognitive symptoms, in addition to a diverse spectrum of movement disorders. This poses a distinct challenge in diagnosis and management. We here describe the spectrum of movement disorders, accompanied with detailed video recordings, in seven cases of juvenile‐onset HD. Our findings highlight early cognitive and behavioral symptoms, preceding motor symptoms. The diverse movement disorder phenotypes included dystonia, Parkinsonism, myoclonus, and chorea, findings which underscore the heterogeneity of presenting symptoms.

The article describes a method for calculating interpolation coefficients of expansion using Chebyshev polynomials. The method is valid when the desired function is bounded and has a finite number of maxima and minima in a finite domain of interpolation. The essence of the method is that the interpolated desired function can be represented as an expansion in Chebyshev polynomials; then the expansion coefficients are determined using the collocation method by reducing the problem to solving a well-conditioned system of linear algebraic equations for the required coefficients. Using the well-known useful properties of Chebyshev polynomials can significantly simplify the solution of the problem of function interpolation. A technique using the Clenshaw algorithm for summing the series and determining the expansion coefficients of the interpolated function, based on the discrete orthogonality of Chebyshev polynomials of the 1st kind, is outlined.

Abstract Titanium alloys are among the widely used biomedical materials due to their biocompatibility and mechanical performance. It is an indisputable fact that the materials used in this area must be antibacterial. Therefore, in this study, the production of antibacterial Titanium alloys using NanoAg particles for use in biomedical applications was investigated. First, Ti-6Al-4 V titanium alloys were produced by the powder metallurgy method, which includes blending, pressing and sintering processes. Nano silver particles were synthesized by a chemical reduction method using silver nitrate and glucose. The resulting solution was subjected to Ag + ions and glucose determinations, pH and turbidity analysis. Nano Ag application was carried out by two different methods; dipping and coating method. The obtained samples were analyzed by scanning electron microscopy (SEM) and optical microscopy. Additionally, as the main purpose of this study, antibacterial analysis against Escherichia Coli and Staphylococcus Aureus was performed by percentage reduction test. While the coating method was seen to be more successful in antibacterial tests, the overall Nano Ag application performance was found to be higher against Escherichia Coli bacteria. Being that the sample containing 5% Nano Ag titanium alloys produced with the coating technique showed 100% killing effect against both Staphylococcus aureus and Escherichia coli.

En la actualidad, uno de los elementos que ha cobrado protagonismo en la optimización de cultivos es el Silicio (Si), un mineral que tradicionalmente ha sido subestimado, sin embargo, juega un papel vital en el bienestar de las plantas. El objetivo de este estudio fue evaluar el efecto de diferentes fuentes y dosis foliares de Si sobre el desarrollo y asimilación de nutrientes en el cultivo de pimiento. El diseño experimental corresponde a un DCA. Los resultados arrojaron que no hubo diferencias significativas en las variables biométricas, como la altura de la planta, el diámetro del tallo y el número de hojas, flores y frutos, entre los tratamientos de fuentes y dosis de Si. Esto sugiere que las dosis de Si evaluadas no tuvieron un efecto sustancial en el crecimiento general de las plantas de pimiento. Sin embargo, se observaron efectos significativos del Si en la química foliar de las plantas. Los tratamientos con Si mostraron concentraciones más bajas de nitrato y potasio en comparación con el grupo de control. Además, se registraron concentraciones más altas de sodio en algunos tratamientos con Si y los valores de pH tanto en el área foliar como en tejidos vegetales se disminuyeron en los tratamientos con Si 1000 y K4(SiO4). Estos hallazgos indican que el Si puede influir en la química foliar de las plantas de pimiento. En cuanto a la salinidad y la CE, se encontraron diferencias estadísticas en los valores de los extractos de hojas y de tallo más peciolo.

The study analyzes whether the type of shareholding control (dispersed, shared, or dominant) affects agency conflicts by investigating the relationship between shareholding control, ownership concentration, and firm value. The sample is a panel data comprising 1977 firm-year observations from 167 Brazilian firms in the period 2010–2022. Our results show that shared control creates value, whereas dominant control destroys firm value. Voting rights concentration and cash-flow rights reduce the value of firms with dispersed and shared control. However, at firms with dominant control, these firm characteristics increase firm value. Excess voting rights, in turn, destroy the value of firms with shared and dominant control. Our evidence shows that the type of shareholding control influences the nature and magnitude of agency conflicts and the relationship between ownership concentration and firm value. Thus, within an institutional environment, agency conflicts may differ among firms, depending on the type of shareholding control.

Abstract In many industrialised countries, sodium intake exceeds the nutritional guidelines. High sodium intake has been associated with health problems, such as arterial hypertension and, consequently, a higher health risk of cardiovascular disease. The aim of this study was to evaluate overall quality of salamis with reduced sodium content by analysing aldehydes, proteolysis, and lipolysis, as well as to verify the correlation between sensory acceptance and volatile compounds. Four formulations were prepared replacing NaCl by a mixture of KCI and CaCl2. Two controls, one with a high level and the other with a low NaCl level were also included in the study. Water activity and pH levels were monitored in all samples. Volatile compounds were measured, in particular, hexanal, 2,4-decadienal and 3-methylbutanal. Finally, a sensory acceptance test was carried out using potential consumers. The results highlighted a relation between aldehyde concentration and sensory acceptance, hexanal/3-methybutanal ratio, that may be a marker of partial NaCl substitution in salami. Thus, our results may be used to guide the use of NaCl substitution by KCl/CaCl2 in terms of volatile compounds. Graphical Abstract

Abstract Current quantum key distribution (QKD) networks focus almost exclusively on transporting secret keys at the highest possible rate. Consequently, they are built as mostly fixed, ad hoc, logically, and physically isolated infrastructures designed to avoid any penalty to the quantum channel. This architecture is neither scalable nor cost-effective and future, real-world deployments will differ considerably. The structure of the MadQCI QKD network presented here is based on disaggregated components and modern paradigms especially designed for flexibility, upgradability, and facilitating the integration of QKD in the security and telecommunications-networks ecosystem. These underlying ideas have been tested by deploying many QKD systems from several manufacturers in a real-world, multi-tenant telecommunications network, installed in production facilities and sharing the infrastructure with commercial traffic. Different technologies have been used in different links to address the variety of situations and needs that arise in real networks, exploring a wide range of possibilities. Finally, a set of realistic use cases has been implemented to demonstrate the validity and performance of the network. The testing took place during a period close to three years, where most of the nodes were continuously active.

Objectives: To investigate the tet(X) gene, a determinant of tigecycline resistance, in the emerging pathogen Elizabethkingia meningoseptica and its association with an integrative and conjugative element (ICE). Methods: All E. meningoseptica genomes from the National Center for Biotechnology Information (n = 87) were retrieved and annotated for resistome searches using the CARD database. A phylogenic analysis was performed based on the E. meningoseptica core genome. The ICE was identified through comparative genomics with other ICEs occurring in Elizabethkingia spp. Results: Phylogenetic analysis revealed E. meningoseptica genomes from six countries distributed across different lineages, some of which persisted for years. The common resistome of these genomes included blaBlaB, blaCME, blaGOB, ranA/B, aadS, and catB (genes associated with resistance to β-lactams, aminoglycosides, and chloramphenicol). Some genomes also presented additional resistance genes (dfrA, ereD, blaVEB, aadS, and tet(X)). Interestingly, tet(X) and aadS were located in an ICE of 49 769 bp (ICEEmSQ101), which was fully obtained from the E. meningoseptica SQ101 genome. We also showed evidence that the other 27 genomes harboured this ICE. The distribution of ICEEmSQ101, carrying tet(X), was restricted to a single Chinese lineage. Conclusions: The tet(X) gene is not prevalent in the species E. meningoseptica, as previously stated for the genus Elizabethkingia, since it is present only in a single Chinese lineage. We identified that several E. meningoseptica genomes harboured an ICE that mobilized the Elizabethkingia tet(X) gene and exhibited characteristics similar to the ICEs of other Flavobacteria, which would favour their transmission in this bacterial family.

Abstract A key aspect of sustainable bioeconomy is the recirculation of renewable, agricultural waste streams as substrates for microbial production of high-value compounds. One approach is the bioconversion of corn stover, an abundant maize crop byproduct, using the fungal maize pathogen Ustilago maydis. U. maydis is already used as a unicellular biocatalyst in the production of several industrially-relevant compounds using plant biomass hydrolysates. In this study, we demonstrate that U. maydis can grow using untreated corn stover as its sole carbon source. We developed a small-scale bioreactor platform to investigate U. maydis processing of corn stover, combining online monitoring of fungal growth and metabolic activity profiles with biochemical analyses of the pre- and post-fermentation residues. Our results reveal that U. maydis primarily utilizes soluble sugars i.e., glucose, sucrose and fructose present in corn stover, with only limited exploitation of the abundant lignocellulosic carbohydrates. Thus, we further explored the biotechnological potential of enhancing U. maydis´ lignocellulosic utilization. Additive performance improvements of up to 120 % were achieved when using a maize mutant with increased biomass digestibility, co-fermentation with a commercial cellulolytic enzyme cocktail, and exploiting engineered fungal strains expressing diverse lignocellulose-degrading enzymes. This work represents a key step towards scaling up the production of sustainable compounds from corn stover using U. maydis and provides a tool for the detailed monitoring of the fungal processing of plant biomass substrates. Graphical abstract

Abstract Background Cardiovascular disease is a major cause of morbidity in an aging HIV population. However, risk estimation with the most frequent equations usually classifies HIV patients as having a low or moderate risk. Several studies have described a very high prevalence of subclinical atherosclerosis in a middle-aged, non-HIV population. There is insufficient body of knowledge to understand if this is the case in people living with HIV (PLWH). We aim to calculate the proportion of patients with subclinical atherosclerosis in a single site cohort of HIV-infected subjects. Methods We have analyzed chronically HIV infected adults (≥ 18 years) who were on active follow-up in an HIV unit specialized in the care of cardiovascular health. The most recent clinical visit and vascular ultrasonography were used to assess the objectives of our research. Our primary objective was to describe the proportion of participants with subclinical atherosclerosis (focal protrusion into the lumen > 0.5 mm or > 50% of the surrounding IMT or a diffuse thickness > 1.5 mm) in a single site cohort of PLWH. Carotid and iliofemoral territories were evaluated. As a secondary objective we have run a multivariate analysis to determine which HIV and non-HIV factors might be related with the presence of atherosclerotic plaques. Findings We included a total of 463 participants between November 2017 to October 2019. Subjects were predominantly male (84.2%) with a mean age of 48.8 years (SD 10.7). Hypercholesterolemia (36%) was the most prevalent comorbidity followed by Hypertension (18%) and Hypertriglyceridemia (16%). Mean duration of HIV infection is 12.3 years. Overall, participants had been receiving cART for a median of 9.5 years. Subclinical atherosclerosis was found in 197 subjects (42.5%; CI 95% [38.0–47.2]). The disease was found more frequently in the femoral arteries (37.8%) than in the carotid vascular bed (18.6%). Despite some HIV factors correlated with the presence of plaques in a univariate analysis (e.g., time with HIV-1 RNA > 50 copies/mL or time from HIV diagnosis), the only two explanatory factors that remained associated with the presence of atherosclerotic plaques in the multivariate analysis were smoking (OR 5.47, 95% CI 3.36 – 8.90) and age (OR 1.13, 95%CI 1.10 – 1.16). Interpretation We have found a very high prevalence of subclinical atherosclerosis among our cohort of PLWH. Despite having analyzed several HIV factors, age and smoking have been found to be the only factors associated with the development of atherosclerotic plaques.

Abstract Background Malaria is the parasitic disease with the highest morbimortality worldwide. The World Health Organization (WHO) estimates that there were approximately 249 million cases in 2022, of which 3.4% were in Angola. Diagnosis is based on parasite identification by microscopy examination, antigen detection, and/or molecular tests, such as polymerase chain reaction (PCR). This study aimed to evaluate the usefulness of real-time PCR as a diagnostic method for malaria in an endemic area (Cubal, Angola). Methods A cross-sectional study was carried out at the Hospital Nossa Senhora da Paz in Cubal, Angola, including 200 patients who consulted for febrile syndrome between May and July 2022. From each patient, a capillary blood sample was obtained by finger prick for malaria field diagnosis [microscopy and rapid diagnostic test (RDT)] and venous blood sample for real-time PCR performed at the Hospital Universitario Vall d’Hebron in Barcelona, Spain. Any participant with a positive result from at least one of these three methods was diagnosed with malaria. Results Of the 200 participants included, 54% were female and the median age was 7 years. Malaria was diagnosed by at least one of the three techniques (microscopy, RDT, and/or real-time PCR) in 58% of the participants, with RDT having the highest percentage of positivity (49%), followed by real-time PCR (39.5%) and microscopy (33.5%). Of the 61 discordant samples, 4 were only positive by microscopy, 13 by real-time PCR, and 26 by RDT. Plasmodium falciparum was the most frequent species detected (90.63%), followed by P. malariae (17.19%) and P. ovale (9.38%). Coinfections were detected in ten participants (15.63%): six (60%) were caused by P. falciparum and P. malariae, three (30%) by P. falciparum and P. ovale, and one (10%) triple infection with these three species. In addition, it was observed that P. falciparum and P. malariae coinfection significantly increased the parasite density of the latter. Conclusions RDT was the technique with the highest positivity rate, followed by real-time PCR and microscopy. The results of the real-time PCR may have been underestimated due to suboptimal storage conditions during the transportation of the DNA eluates. However, real-time PCR techniques have an important role in the surveillance of circulating Plasmodium species, given the epidemiological importance of the increase in non-falciparum species in the country, and can provide an estimate of the intensity of infection. Graphical abstract

Abstract Advances in omics technologies have enabled the in-depth study of microbial communities and their metabolic profiles from all environments. Here metagenomes were sampled from piranha (Serrasalmus rhombeus) and from river water from the Rio São Benedito (Amazon Basin). Shotgun metagenome sequencing was used to explore diversity and to test whether fish microbiomes are a good proxy for river microbiome studies. The results showed that the fish microbiomes were not significantly different from the river water microbiomes at higher taxonomic ranks. However, at the genus level, fish microbiome alpha diversity decreased, and beta diversity increased. This result repeated for functional gene abundances associated with specific metabolic categories (SEED level 3). A clear delineation between water and fish was seen for beta diversity. The piranha microbiome provides a good and representative subset of its river water microbiome. Variations seen in beta biodiversity were expected and can be explained by temporal variations in the fish microbiome in response to stronger selective forces on its biodiversity. Metagenome assembled genomes construction was better from the fish samples. This study has revealed that the microbiome of a piranha tells us a lot about its river water microbiome and function.

Studying pore networks in rocks is critical for understanding reservoir properties, with mercury intrusion porosimetry (MIP) being a key laboratory method. MIP involves capillary intrusion of mercury, with intrusion pressure (P) related to capillary diameter (d) by the Washburn equation, incorporating mercury properties like contact angle (θ) and surface tension (γ). While a constant contact angle of 140° is typically assumed for MIP, it can vary based on rock mineralogy and surface roughness. This study aims to analyze how contact angle variations and surface roughness affect MIP analysis of carbonate rocks. Initially, contact angle data was obtained for calcite, dolomite, and quartz with varying roughness levels. Synthetic rocks were then constructed using these minerals. MIP was performed using the typical 140° contact angle and a calculated contact angle from the Cassie model, which considers surface composition fraction. Natural rock MIP analysis followed, with contact angles varying due to mineral composition and roughness. The study found higher contact angles than the standard 140°, affecting pore size distributions up to 30%. Natural rock pore network curves were adjusted based on synthetic rock data analysis. These findings emphasize the need for accurate contact angle selection in MIP for precise pore distribution analysis and contribute to the further study of carbonate rocks.

Abstract Background Parasitic neglected tropical diseases (NTDs) or ‘infectious diseases of poverty’ continue to affect the poorest communities in the world, including in the Philippines. Socio-economic conditions contribute to persisting endemicity of these infectious diseases. As such, examining these underlying factors may help identify gaps in implementation of control programs. This study aimed to determine the prevalence of schistosomiasis and soil-transmitted helminthiasis (STH) and investigate the role of socio-economic and risk factors in the persistence of these diseases in endemic communities in the Philippines. Methods This cross-sectional study involving a total of 1,152 individuals from 386 randomly-selected households was conducted in eight municipalities in Mindanao, the Philippines. Participants were asked to submit fecal samples which were processed using the Kato-Katz technique to check for intestinal helminthiases. Moreover, each household head participated in a questionnaire survey investigating household conditions and knowledge, attitude, and practices related to intestinal helminthiases. Associations between questionnaire responses and intestinal helminth infection were assessed. Results Results demonstrated an overall schistosomiasis prevalence of 5.7% and soil-transmitted helminthiasis prevalence of 18.8% in the study population. Further, the household questionnaire revealed high awareness of intestinal helminthiases, but lower understanding of routes of transmission. Potentially risky behaviors such as walking outside barefoot and bathing in rivers were common. There was a strong association between municipality and prevalence of helminth infection. Educational attainment and higher “practice” scores (relating to practices which are effective in controlling intestinal helminths) were inversely associated with soil-transmitted helminth infection. Conclusion Results of the study showed remaining high endemicity of intestinal helminthiases in the area despite ongoing control programs. Poor socio-economic conditions and low awareness about how intestinal helminthiases are transmitted may be among the factors hindering success of intestinal helminth control programs in the provinces of Agusan del Sur and Surigao del Norte. Addressing these sustainability gaps could contribute to the success of alleviating the burden of intestinal helminthiases in endemic areas.