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Abstract Childhood obesity poses a significant public health challenge, yet the molecular intricacies underlying its pathobiology remain elusive. Leveraging extensive multi-omics profiling (methylome, miRNome, transcriptome, proteins and metabolites) and a rich phenotypic characterization across two parts of Europe within the population-based Human Early Life Exposome project, we unravel the molecular landscape of childhood obesity and associated metabolic dysfunction. Our integrative analysis uncovers three clusters of children defined by specific multi-omics profiles, one of which characterized not only by higher adiposity but also by a high degree of metabolic complications. This high-risk cluster exhibits a complex interplay across many biological pathways, predominantly underscored by inflammation-related cascades. Further, by incorporating comprehensive information from the environmental risk-scape of the critical pregnancy period, we identify pre-pregnancy body mass index and environmental pollutants like perfluorooctanoate and mercury as important determinants of the high-risk cluster. Overall, our work helps to identify potential risk factors for prevention and intervention strategies early in the life course aimed at mitigating obesity and its long-term health consequences.

The study of cyclic peptides (CPs) and self-assembling cyclic peptide nanotubes (SCPNs) is pivotal in advancing applications in diverse fields such as biomedicine, nanoelectronics, and catalysis. Recognizing the limitations in the experimental study of these molecules, this article introduces CYCLOPEp Builder, a comprehensive web-based application designed to facilitate the design, simulation, and visualization of CPs and SCPNs. The tool is engineered to generate molecular topologies, essential for conducting Molecular Dynamics simulations that span All-Atom to Coarse-Grain resolutions. CYCLOPEp Builder's user-friendly interface simplifies the complex process of molecular modeling, providing researchers with the ability to readily construct CPs and SCPNs. The platform is versatile, equipped with various force fields, and capable of producing structures ranging from individual CPs to complex SCPNs with different sequences, offering parallel and antiparallel orientations among them. By enhancing the capacity for detailed visualization of molecular assemblies, CYCLOPEp Builder improves the understanding of CP and SCPN molecular interactions. This tool is a step forward in democratizing access to sophisticated simulations, offering an invaluable resource to the scientific community engaged in the exploration of supramolecular structures. CYCLOPEp is accessible at http://cyclopep.com/

The increasing consumption of chia seeds is followed by a growing interest in their nutritional and toxicological characterization. To assess the characterization of the essential and PTEs of this novel food, 20 samples of conventional and organic chia seeds available on the European market were analyzed using ICP-OES. Then, the dietary exposure to these elements was assessed. An exhaustive investigation into the metal content of this food serves to elucidate the paucity of existing knowledge. The results show that the levels of essential elements are similar in both types of production, while the levels of PTEs are higher in the organic samples. The exposure assessment indicates that Mn contributes the most among the essential elements, followed by Cu in women. Exposure to PTEs through doses of 50 g/day of chia seeds analyzed would hardly pose short-term health risks as the contributions are below 10%, except for Sr, although they could produce a long-term toxicological risk. To promote safety in chia seed consumption, it is recommended to encourage responsible and moderate consumption, continue monitoring PTE levels in this novel food, and establish concentration limits for PTEs in future European regulations.

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.

Background and objective: The role of pelvic lymph node dissection (PLND) for prostate cancer is still controversial. This study aims to compare the outcomes of PLND between extraperitoneal single-port (SP eRARP) and transperitoneal multiport (MP tRARP) robotic-assisted radical prostatectomy. Methods: This was a retrospective analysis from our single-center database for patients who underwent SP eRARP or MP tRARP with PLND between 2015 and 2023. The primary endpoint was to analyze and compare specific data related to PLND between the two populations by the detection of pN+ patients, the total number of lymph nodes removed, and the number of positive lymph nodes removed. The secondary endpoints included comparing major complications, lymphoceles, and biochemical recurrence between the two cohorts of the study. Key findings and limitations: A total of 293 patients were included, with 85 (29%) undergoing SP eRARP and 208 (71%) undergoing MP tRARP. SP eRARP showed significant differences in PLND extension from MP tRARP, while MP tRARP yielded more lymph nodes (p

Abstract Providing stable and clean energy sources is a necessity for the increasing demands of humanity. Energy produced by Deuterium (D) and Tritium (T) fusion reactions, in particular in tokamaks, is a promising path towards that goal. However, there is little experience with plasmas formed by D-T mixtures, since most of the experiments are currently performed in pure D. After more than 20 years, the Joint European Torus (JET) has carried out new D-T experiments with the aim of exploring some of the unique characteristics expected in future fusion reactors, such as the presence of highly energetic ions in low plasma rotation conditions. A new stable, high confinement and impurity-free D-T regime, with reduction of energy losses with respect to D, has been found. Multiscale physics mechanisms critically determine the thermal confinement. These crucial achievements importantly contribute to the establishment of fusion energy generation as an alternative to fossil fuels.

Aim of study: The loss of forest cover is a global problem that alters ecosystems, contributing to carbon emissions. This study measured the soil organic carbon (SOC) at different soil depths in tropical dry forests of the Huallaga Central in the Peruvian Amazon. Area of study: San Martín Region, Peruvian Amazon. Material and methods: A total of 24 plots of 100 m2 were selected in primary (~200 years), intervened (~50 years since intervention), and deforested forests (10 years ago), with 120 soil samples collected across five depths. Soil texture (hydrometer), bulk density (cylinder method), SOC content, SOC density, and erodibility (K parameter) were calculated. Main results: SOC content in the 0-20 cm soil horizon was 79.5±21.3 t ha-1 for the primary forest, 58.5±11.8 t ha-1 for the intervened forest, and 41.8±10 t ha-1 for the deforested forest. A soil erodibility K of 0.065 was observed for primary forests and 0.076 and 0.093 for intervened and deforested forests. In average, the SOC density obtained in this study was 7.6±5.1 t ha-1 in the primary forest, 6.2±3.6 t ha-1 in the intervened forest, and 4.7±2.7 in the deforested forest. Research highlights: Primary forests had the highest SOC content and SOC density, followed by intervened and deforested forests, while the opposite pattern was found for soil erodibility. These patterns were especially marked in the first 40 cm of soil depth.

The importance of maintaining data privacy and complying with regulatory requirements is highlighted especially when sharing omic data between different research centers. This challenge is even more pronounced in the scenario where a multi-center effort for collaborative omics studies is necessary. OmicSHIELD is introduced as an open-source tool aimed at overcoming these challenges by enabling privacy-protected federated analysis of sensitive omic data. In order to ensure this, multiple security mechanisms have been included in the software. This innovative tool is capable of managing a wide range of omic data analyses specifically tailored to biomedical research. These include genome and epigenome wide association studies and differential gene expression analyses. OmicSHIELD is designed to support both meta- and mega-analysis, so that it offers a wide range of capabilities for different analysis designs. We present a series of use cases illustrating some examples of how the software addresses real-world analyses of omic data.

IntroductionSecondary forests and coffee cultivation systems with shade trees might have great potential for carbon sequestration as a means of climate change adaptation and mitigation. This study aimed to measure carbon stocks in coffee plantations under different managements and secondary forest systems in the Peruvian Amazon rainforest (San Martín Region).MethodsThe carbon stock in secondary forest trees was estimated using allometric equations, while carbon stocks in soil, herbaceous biomass, and leaf litter were determined through sampling and laboratory analysis.ResultsThe biomass carbon stock in secondary forests was 132.2 t/ha, while in coffee plantations with Inga sp. shade trees was 118.2 t/ha. Carbon stocks were 76.5 t/ha in coffee with polyculture farming, while the lowest amount of carbon was found in coffee without shade trees (31.1 t/ha). The carbon sequestered by coffee plants in all agroforestry systems examined had an average of 2.65 t/ha, corresponding to 4.63 % of the total carbon sequestered, being the highest stored in the coffee system with Inga sp. shade trees. A higher content of glomalin-related soil proteins (GRSP) was found in coffee without shade trees, with 18.5 mg/g.DiscussionThese results point to Inga sp. as a compatible model of shade system for coffee farms. However, broader-scale time-average measurements and carbon dioxide emissions should be assessed in these study systems to have a full understanding of their climate impacts.

Although chimeric antigen receptor (CAR) T cell therapy has revolutionized type B cancer treatment, efficacy remains limited in various lymphomas and solid tumors. Reinforcing conventional CAR-T cells to release cytokines can improve their efficacy but also increase safety concerns. Several strategies have been developed to regulate their secretion using minimal promoters that are controlled by chimeric proteins harboring transactivators. However, these chimeric proteins can disrupt the normal physiology of T cells. Here, we present the first transactivator-free anti-CD19 CAR-T cells able to control IL-18 expression (iTRUCK19.18) under ultra-low doses of doxycycline and without altering cellular fitness. Interestingly, IL-18 secretion requires T cell activation in addition to doxycycline, allowing the external regulation of CAR-T cell potency. This effect was translated into an increased CAR-T cell antitumor activity against aggressive hematologic and solid tumor models. In a clinically relevant context, we generated patient-derived iTRUCK19.18 cells capable of eradicating primary B cells tumors in a doxycycline-dependent manner. Furthermore, IL-18-releasing CAR-T cells polarized pro-tumoral macrophages toward an antitumoral phenotype, suggesting potential for modulating the tumor microenvironment. In summary, we showed that our platform can generate exogenously controlled CAR-T cells with enhanced potency and in the absence of transactivators.

High-grade serious ovarian cancer (HGSOC) is an aggressive malignancy that remains refractory to current immunotherapies. While advanced stage disease has been extensively studied, the cellular and molecular mechanisms that promote early immune escape in HGSOC remain largely unexplored. Here, we report that primary HGSO tumors program neutrophils to inhibit T cell anti-tumor function by activating the endoplasmic reticulum (ER) stress sensor IRE1α. We found that intratumoral neutrophils exhibited overactivation of ER stress response markers compared with their counterparts at non-tumor sites. Selective deletion of IRE1α in neutrophils delayed primary ovarian tumor growth and extended the survival of mice with HGSOC by enabling early T cell-mediated tumor control. Notably, loss of IRE1α in neutrophils sensitized tumor-bearing mice to PD-1 blockade, inducing HGSOC regression and long-term survival in ~ 50% of the treated hosts. Hence, neutrophil-intrinsic IRE1α facilitates early adaptive immune escape in HGSOC and targeting this ER stress sensor might be used to unleash endogenous and immunotherapy-elicited immunity that controls metastatic disease.

Introduction: Granular Cell Tumors (GCTs) are rare soft tissue neoplasms originating from Schwann cells, often benign but mimicking breast carcinoma clinically and radiologically. Case presentation: A 17-year-old female with a second-degree family history of breast cancer presented with a painful left breast mass (∼3 cm) persisting for three years. Initial evaluation with fine needle aspiration (FNA) suggested a benign lipoma, but imaging reported BIRADS IV mass. Mammography revealed an ovoid mass with irregular margins, Sono-mammogram reported heterogeneous slightly lobulated mass with excentric sonolucent of 3 x 2.4 × 1.8 cm, no increased vascularity on sono-doppler and core needle biopsy confirmed a GCT, positive for S-100 and CD68. The patient was taken to the operating room for surgical excision. A 4 cm curvilinear incision was made over the left breast mass, just lateral to the nipple at the 3 o'clock position. En-bloc excision of the mass was carried out with 1 cm margins. The specimen was removed and sent for frozen section analysis that confirmed the cytological diagnosis of a granular cell tumor with clear margins. The excised mass was sent for permanent section to pathology. Final histopathology confirmed a benign GCT with free margins. Due to the infiltrative nature of the tumor, a second excision in similar fashion was required to obtain wider margins, which was uneventful. Clear margins were pursued due to the tumor's infiltrative nature and patient's family history of breast cancer, despite the low risk of recurrence with positive margins. The patient remains clinically disease-free at three-year follow-up. Conclusion: Granular cell tumors of the breast, though benign, are often mistaken for carcinoma due to their clinical similarity. Complete excision with clear margins, which may require re-excision due to their infiltrative nature, is crucial to prevent recurrence.

Abstract People affected by psychotic, depressive and developmental disorders are at a higher risk for alcohol and tobacco use. However, the further associations between alcohol/tobacco use and symptoms/cognition in these disorders remain unexplored. We identified multimodal brain networks involving alcohol use (n = 707) and tobacco use (n = 281) via supervised multimodal fusion and evaluated if these networks affected symptoms and cognition in people with psychotic (schizophrenia/schizoaffective disorder/bipolar, n = 178/134/143), depressive (major depressive disorder, n = 260) and developmental (autism spectrum disorder/attention deficit hyperactivity disorder, n = 421/346) disorders. Alcohol and tobacco use scores were used as references to guide functional and structural imaging fusion to identify alcohol/tobacco use associated multimodal patterns. Correlation analyses between the extracted brain features and symptoms or cognition were performed to evaluate the relationships between alcohol/tobacco use with symptoms/cognition in 6 psychiatric disorders. Results showed that (1) the default mode network (DMN) and salience network (SN) were associated with alcohol use, whereas the DMN and fronto-limbic network (FLN) were associated with tobacco use; (2) the DMN and fronto-basal ganglia (FBG) related to alcohol/tobacco use were correlated with symptom and cognition in psychosis; (3) the middle temporal cortex related to alcohol/tobacco use was associated with cognition in depression; (4) the DMN related to alcohol/tobacco use was related to symptom, whereas the SN and limbic system (LB) were related to cognition in developmental disorders. In summary, alcohol and tobacco use were associated with structural and functional abnormalities in DMN, SN and FLN and had significant associations with cognition and symptoms in psychotic, depressive and developmental disorders likely via different brain networks. Further understanding of these relationships may assist clinicians in the development of future approaches to improve symptoms and cognition among psychotic, depressive and developmental disorders.

Abstract The biological and technological importance of anion-mediated processes has made the development of improved methods for the selective recognition of anions one of the most relevant research topics today. The hydration sphere of anions plays an important role in the functions performed by anions by forming a variety of cluster complexes. Here we describe a supramolecular capsule that recognizes hydrated anion clusters. These clusters are most likely composed of three ions that form hydrated C3 symmetry complexes that are entrapped within the supramolecular capsule of the same symmetry. The capsule is made of self-assembled α,γ-cyclic peptide containing amino acid with by five-membered rings and equipped with a tris(triazolylethyl)amine cap. To recognise the hydrated anion clusters, the hexapeptide capsule must disassemble to entrap them between its two subunits.

Introducción: La pandemia del COVID-19 revolucionó muchos aspectos de la vida de las personas y aquellos pacientes que necesitaban una rehabilitación luego de una artroplastia total de cadera (ATC) no fueron la excepción. Objetivo: Determinar si existe alguna diferencia en los resultados funcionales entre la rehabilitación supervisada y la autoadministrada después de una ATC. Materiales y Métodos: Se recolectaron datos de 2 grupos de pacientes: los operados de ATC unilateral que realizaron rehabilitación supervisada y aquellos operados durante la pandemia, que recibieron rehabilitación sin supervisión, autoadministrada. Se compararon los resultados funcionales de ambos grupos a los 3 meses y al año de la cirugía mediante el Harris Hip Score modificado (HHSm) y el Forgotten Joint Score (FJS). Resultados: No se encontraron diferencias significativas en el HHS entre ambos grupos a los 3 ni a los 12 meses (p 0,18). Por el contrario, se observó una diferencia estadísticamente significativa (p

We present three new approaches for solving first-order quasi-linear partial differential equations (PDEs) with iterative methods of high stability and low cost. The first is a new numerical version of the method of characteristics that converges efficiently, under certain conditions. The next two approaches initially apply the unconditionally stable Crank–Nicolson method, which induces a system of nonlinear equations. In one of them, we solve this system by using the first optimal schemes for systems of order four (Ermakov’s Hyperfamily). In the other approach, using a new technique called JARM decoupling, we perform a modification that significantly reduces the complexity of the scheme, which we solve with scalar versions of the aforementioned iterative methods. This is a substantial improvement over the conventional way of solving the system. The high numerical performance of the three approaches is checked when analyzing the resolution of some examples of nonlinear PDEs.

Introduction: Angiolipomatosis is a rare benign condition involving subcutaneous fat and blood vessels, particularly uncommon in pediatric patients. Case presentation: An 11-year-old male presented with multiple firm, non-tender masses in the right gluteal and perianal regions, the largest measuring 8 cm for approximately 8 months duration. The patient underwent staged surgical excisions under general anesthesia due to extensive disease burden. In the first stage, perianal and medial gluteal masses were excised. Lipomatous masses were carefully dissected from the external anal sphincter to the posterior superior iliac spine (PSIS) with preservation of the external anal sphincter. The procedure was well tolerated, but the patient developed a postoperative wound infection, requiring intravenous antibiotics, debridement, and the creation of a loop colostomy to control wound contamination. Six weeks later, a second-stage excision removed the remaining gluteal masses, including a palpable mass measuring 8 x 4 × 2.5 cm. Hemostasis was achieved, and a Jackson-Pratt drain was placed to manage post-op wound fluid accumulation. The patient recovered well after both surgeries and at the 3-month follow-up, there were no complications. Pathological analysis confirmed angiolipomatosis in the gluteal region and diffuse lipomatosis in the perianal region. No recurrence was observed over a 3-year follow-up period. Conclusion: Angiolipomatosis should be considered as a differential diagnosis for pediatric soft tissue masses in uncommon locations like the gluteal and perianal regions. Atypical presentations can be successfully managed with careful surgical planning helping to avoid unnecessary radical procedures. A staged approach is recommended when encountering diffuse disease, as in this case, and consideration should be given to diverting ostomy if wound contamination is a concern.

ABSTRACT Allosteric HIV-1 integrase (IN) inhibitors (ALLINIs) are investigational antiretroviral agents that potently impair virion maturation by inducing hyper-multimerization of IN and inhibiting its interaction with viral genomic RNA. The pyrrolopyridine-based ALLINI pirmitegravir (PIR) has recently advanced into phase 2a clinical trials. Previous cell culture-based viral breakthrough assays identified the HIV-1(Y99H/A128T IN) variant that confers substantial resistance to this inhibitor. Here, we have elucidated the unexpected mechanism of viral resistance to PIR. Although both Tyr99 and Ala128 are positioned within the inhibitor binding V-shaped cavity at the IN catalytic core domain (CCD) dimer interface, the Y99H/A128T IN mutations did not substantially affect the direct binding of PIR to the CCD dimer or functional oligomerization of full-length IN. Instead, the drug-resistant mutations introduced a steric hindrance at the inhibitor-mediated interface between CCD and C-terminal domain (CTD) and compromised CTD binding to the CCDY99H/A128T + PIR complex. Consequently, full-length INY99H/A128T was substantially less susceptible to the PIR-induced hyper-multimerization than the WT protein, and HIV-1(Y99H/A128T IN) conferred >150-fold resistance to the inhibitor compared with the WT virus. By rationally modifying PIR, we have developed its analog EKC110, which readily induced hyper-multimerization of INY99H/A128T in vitro and was ~14-fold more potent against HIV-1(Y99H/A128T IN) than the parent inhibitor. These findings suggest a path for developing improved PIR chemotypes with a higher barrier to resistance for their potential clinical use.IMPORTANCEAntiretroviral therapies save the lives of millions of people living with HIV (PLWH). However, the evolution of multi-drug-resistant viral phenotypes is a major clinical problem, and there are limited or no treatment options for heavily treatment-experienced PLWH. Allosteric HIV-1 integrase inhibitors (ALLINIs) are a novel class of antiretroviral compounds that work by a unique mechanism of binding to the non-catalytic site on the viral protein and inducing aberrant integrase multimerization. Accordingly, ALLINIs potently inhibit both wild-type HIV-1 and all drug-resistant viral phenotypes that have so far emerged against currently used therapies. Pirmitegravir, a highly potent and safe investigational ALLINI, is currently advancing through clinical trials. Here, we have elucidated the structural and mechanistic bases behind the emergence of HIV-1 integrase mutations in infected cells that confer resistance to pirmitegravir. In turn, our findings allowed us to rationally develop an improved ALLINI with substantially enhanced potency against the pirmitegravir-resistant virus.

Este estudio se dirigió a evaluar la eficacia de intervenciones no farmacológicas más allá de las conocidas y efectivas intervenciones en el estilo de vida como complemento al tratamiento de pacientes adultos con diagnóstico de hipertensión arterial, factor de riesgo significativo para enfermedades cardiovasculares mortales. Entre las intervenciones evaluadas, se incluyeron las terapias alternativas, como la medicina tradicional china y la acupuntura (tres estudios), las terapias mente-cuerpo (diez estudios) y la suplementación con productos dietéticos/nutracéuticos (diez estudios). Los resultados sugieren que algunas de estas terapias pueden ser prometedoras como complemento al tratamiento antihipertensivo. Entre las terapias mencionadas, se destacan la acupresión auricular, el taichi, el yoga, el qigong y la meditación. Además, ciertos nutracéuticos y fitoterapéuticos, como los ácidos grasos omega 3, la coenzima Q10, la vitamina C, los probióticos, el resveratrol, las isoflavonas de soja, el extracto de ajo y el aceite de oliva extravirgen, pueden ser recomendados como parte de una dieta saludable, como la dieta mediterránea o DASH, reconocida por su impacto en el riesgo cardiovascular. En conclusión, en lo que respecta a las políticas públicas dirigidas al manejo integral de las enfermedades crónicas no transmisibles, estas terapias, dentro del manejo no farmacológico, pueden complementar eficazmente el tratamiento de la hipertensión arterial, brindando a los pacientes opciones adicionales para controlar su presión arterial y mejorar su salud cardiovascular. Sin embargo, se necesita más investigación para confirmar su eficacia y seguridad a largo plazo.

Entrepreneurial ecosystems (EEs) are a growing focus for policymakers and academics seeking to foster innovation and economic growth. While existing literature has analysed various aspects of EEs, limited research has examined how public policies can contribute to their development. Through a single-case study, this study addresses this gap by analysing the role of a regional government in overcoming the challenges of building an EE. We explore the creation and development of the Biscay Startup Bay (BSB) EE in Bilbao City (Bizkaia, Basque Country, Spain). We describe the unique framework that they crafted and implemented, highlighting the key attributes that generate value for all stakeholders. This single-case study of the BSB EE in Spain offers valuable insights for policymakers seeking to design and implement successful Open Innovation-driven approaches to creating and developing regional EEs.

Not available.

La parálisis supranuclear progresiva (PSP) es un parkinsonismo atípico poco común, caracterizado por la presencia de agregados de la proteína tau y determinado por un amplio espectro de características clínicas. El diagnóstico definitivo es post mortem y se identifica a través de la presencia de muerte neuronal, gliosis y agregados de la proteína tau presentados en forma de marañas neurofibrilares con apariencia globosa en regiones como el núcleo subtalámico, la sustancia nigra y el globo pálido. Los hallazgos en los estudios de imagen y los biomarcadores en fluidos no son suficientes para el diagnóstico certero, pero son usados para descartar patologías similares debido a que aún no existen biomarcadores específicos para esta enfermedad. El tratamiento actual se centra en la disminución de la sintomatología, aunque las terapias emergentes buscan contrarrestar los mecanismos fisiopatológicos. Los modelos celulares constituyen una buena herramienta para determinar los mecanismos moleculares subyacentes a la PSP. En México, la PSP ha sido poco estudiada y a menudo su diagnóstico se confunde con la enfermedad de Parkinson; por su gran impacto socioeconómico y en la salud de los pacientes, sus familiares y cuidadores, se requiere más investigación básica y clínica.

El estudio analiza los sistemas agroproductivos en los cantones de Chone, San Vicente, Sucre, Flavio Alfaro, El Carmen y Bolívar, ubicados en la provincia de Manabí-Ecuador. Se empleó un enfoque descriptivo-exploratorio, no experimental. La muestra consistió en 149 habitantes de la región, quienes proporcionaron información demográfica y detalles sobre sus actividades agrícolas. Los resultados resaltaron la agricultura como la actividad predominante, con más de la mitad de los encuestados dedicados a cultivos de ciclo corto, principalmente maíz, mientras que otros se enfocan en cultivos perennes, especialmente cacao. Además, la producción de ganado bovino, principalmente para la obtención de leche, es una actividad relevante en la provincia. Aunque en menor medida, también se observó participación en la producción de ganado porcino, avicultura y silvicultura, contribuyendo al desarrollo local. No obstante, se identificaron dificultades en infraestructura y falta de innovación tecnológica en todas estas actividades agroproductivas, lo que podría obstaculizar el potencial de crecimiento y desarrollo sostenible en el sector agrícola de la región.

Introduction: Diuretics are the mainstay of maintaining and restoring euvolemia in the management of heart failure. Loop diuretics are often preferred, however, combination diuretic therapy (CDT) with a thiazide diuretic is often used to overcome diuretic resistance and increase diuretic effect. We performed an analysis of the GUIDE-IT study to assess all-cause mortality and time to first hospitalizations in patients necessitating CDT. Methods: Patients from the GUIDE-IT dataset were stratified by their requirement for CDT with a thiazide to achieve euvolemia. A total of 894 patients were analyzed, 733 of which were treated with loop diuretics alone vs 161 used either chlorothiazide or metolazone in addition to loop diuretics. Kaplan-Meir curves were derived with log-rank p-values to evaluate for differences between the groups. Results: There was no significant difference in all-cause mortality regardless of CDT utilization status (mean survival of 612.704 days vs 603.326 days, p = 0.083). On subgroup analysis, there was no significant difference in all-cause mortality amongst those using loop diuretics compared to CDT in the BNP-guided therapy group, (mean survival time 576.385 days vs 620.585 days, p = 0.0523), nor the control group (614.1 days vs 588.9 days; p = 0.5728). Time to first hospitalization was reduced in all using CDT compared to loop diuretics alone (280.5 days vs 407.2 days, p

Background: Some studies have reported that homocysteine, vitamin B12, and folic acid levels are associated with polycystic ovary syndrome (PCOS), whereas other studies yielded controversial results. Objectives: This study aimed to systematize the available evidence of homocysteine, vitamin B12, and folate levels in women with and without PCOS. Design: Systematic review and meta-analysis Data Sources and Methods: A systematic search without language restrictions was performed on PubMed, Ovid/Medline, Scopus, Embase, and Web of Science. In addition, the reference lists of the selected studies were reviewed. The Newcastle–Ottawa Scale was employed to evaluate the quality of studies. The means and standard deviations of the outcomes were pooled as standardized mean differences (SMDs) with 95% confidence intervals (CI). Furthermore, the DerSimonian and Laird method was employed for the quantitative synthesis. Results: A total of 75 studies met the eligibility criteria for at least one outcome. Patients with PCOS had higher circulating homocysteine levels than those without (SMD: 0.82; 95% CI: 0.62–1.02, n = 70 studies, p

Multipolarized nanoantennae are promising for terahertz applications due to their ability to support multiple resonance and polarization sensitivity. This study investigates the behavior of multipolarized gold nanoantennae placed on a Si-SiO2 substrate and compares their performance with antennae in air. The results show that the resonance frequency shifts from 27 THz in the air to 26 THz on the SiSiO2 substrate. SEM and FTIR analysis confirmed the antenna dimensions and optical response, with experimental reflectance spectra revealing resonance at 21 THz and 26 THz. The multi-polarized antenna demonstrated stable performance across different polarization angles compared to traditional dipole antennae, making it suitable for various terahertz applications. These findings provide insights into optimizing nanoantenna design for advanced sensors and communication systems.

Introduction: Avian influenza A H5N1 is a significant global public health threat. Although relevant, systematic reviews about its prevalence in animals are lacking. Methods: We performed a systematic literature review in bibliographic databases to assess the prevalence of H5N1 in animals. A meta-analysis with a random-effects model was performed to calculate the pooled prevalence and 95 % confidence intervals (95%CI). In addition, measures of heterogeneity (Cochran's Q statistic and I2 test) were reported. Results: The literature search yielded 1359 articles, of which 33 studies were fully valid for analysis, including 96,909 animals. The pooled prevalence for H5N1 in birds (n = 90,045, 24 studies) was 5.0 % (95%CI: 4.0–6.0 %; I2 = 99.21); in pigs (n = 3,178, 4 studies) was 1.0 % (95%CI: 0.0–1.0 %); in cats (n = 2,911, 4 studies) was 0.0 % (95%CI: 0.0–1.0 %); and in dogs (n = 479, 3 studies) was 0.0 % (95%CI: 0.0–2.0 %). Conclusions: While the occurrence of H5N1 in animals might be comparatively limited compared to other influenza viruses, its impact on public health can be substantial when it transmits to humans. This virus can potentially induce severe illness and has been linked to previous outbreaks. Therefore, it is essential to closely monitor and comprehend the factors influencing the prevalence of H5N1 in both avian and human populations to develop effective disease control and prevention strategies.

BackgroundUnderstanding individual ovarian hormone cycles and their relationship with health, performance and injuries is highly important to practitioners supporting female athletes. Venous blood sampling is the current gold standard for measuring the ovarian hormones, but the invasive nature of this method presents a major barrier in sport environments. Saliva analysis may offer an alternative method as it is non-invasive, allowing the sample to be collected “in situ”, with relative ease, necessary in applied sport environments.ObjectiveThe aims of this study were: (i) To compare the concentration of progesterone between capillary blood and saliva, (ii) To assess the efficacy of weekly measurements of progesterone for determining if ovulation has occurred in elite eumenorrheic football players, and (iii) To establish a saliva criteria cut-off for establishing ovulation and assessing the sensitivity, specificity and accuracy values of the method.MethodologyTwenty-one professional and semi-professional, Spanish league female football players (18.6 ± 1.5 years, 58.1 ± 6.0 kg, 164.0 ± 4.8 cm) with natural menstrual cycles, completed the study. Capillary blood and saliva samples were collected from each participant on twelve occasions each separated by at least 7 days. All samples were collected in the morning, following an overnight fast.ResultsAccording to luteal phase serum progesterone concentrations, 11 out of 21 (52%) players presented with menstrual irregularities (oligomenorrheic n = 6, anovulatory n = 4, amenorrhoeic n = 1). A significant correlation was observed between plasma and saliva progesterone in the estimated eumenorrheic group (r = 0.80, p = 50 pg/ml and >1.5× follicular baseline has good sensitivity, specificity, and accuracy to indicate ovulation compared to established criteria for serum progesterone.

Introduction: Phthalates, or dieters of phthalic acid, are a ubiquitous type of plasticizer used in a variety of common consumer and industrial products. They act as endocrine disruptors and are associated with increased risk for several diseases. Once in the body, phthalates are metabolized through partially known mechanisms, involving phase I and phase II enzymes. Objective: In this study we aimed to identify common single nucleotide polymorphisms (SNPs) and copy number variants (CNVs) associated with the metabolism of phthalate compounds in children through genome-wide association studies (GWAS). Methods: The study used data from 1,044 children with European ancestry from the Human Early Life Exposome (HELIX) cohort. Ten phthalate metabolites were assessed in a two-void pooled urine collected at the mean age of 8 years. Six ratios between secondary and primary phthalate metabolites were calculated. Genome-wide genotyping was done with the Infinium Global Screening Array (GSA) and imputation with the Haplotype Reference Consortium (HRC) panel. PennCNV was used to estimate copy number variants (CNVs) and CNVRanger to identify consensus regions. GWAS of SNPs and CNVs were conducted using PLINK and SNPassoc, respectively. Subsequently, functional annotation of suggestive SNPs (p-value

La hemorragia masiva por rotura de un pseudoaneurisma de la arteria hipogástrica es una complicación muy rara de la fuga anastomótica colorrectal. Mujer de 41 años con antecedentes de cirugía por cáncer de recto, que debutó con un cuadro de rectorragias masivo y shock hipovolémico secundario a la rotura de un pseudoaneurisma de la arteria hipogástrica como complicación tardía de una fuga de la anastomosis colorrectal. La rotura de un pseudoaneurisma de la arteria hipogástrica se debe tener presente en el diagnostico diferencial de pacientes con rectorragia masiva y antecedentes de dehiscencia de anastomosis colorrectal. La embolización endovascular es actualmente el tratamiento de elección.

Mpox is a zoonotic disease that became epidemic in multiple countries in 2022. There is a lack of published systematic reviews on natural animal infection due to Mpox. We performed a systematic literature review with meta-analysis to assess animal Mpox prevalence. We performed a random-effects model meta-analysis to calculate the pooled prevalence and 95% confidence interval (95%CI) for prevalence studies. After the screening, 15 reports were selected for full-text assessment and included in qualitative and quantitative analyses. Ten reports assessed Mpox infection by molecular or serological tests (n = 2680), yielding a pooled prevalence of 16.0% (95%CI: 3.0–29.0%) for non-human primates; 8.0% (95%CI: 4.0–12.0%) for rodents and 1.0% (95%CI: 0.0–3.0%) for shrews. Further studies in other animals are required to define the extent and importance of natural infection due to Mpox. These findings have implications for public human and animal health. OneHealth approach is critical for prevention and control.

Abstract Background: Loxoscelism refers to a set of clinical manifestations caused by the bite of spiders from the Loxosceles genus. The classic clinical symptoms are characterized by an intense inflammatory reaction at the bite site followed by local necrosis and can be classified as cutaneous loxoscelism. This cutaneous form presents difficult healing, and the proposed treatments are not specific or effective. This study aimed to evaluate the protective effect of mesenchymal stromal cells-derived secretome on dermonecrosis induced by Loxosceles intermedia spider venom in rabbits. Methods: Sixteen rabbits were distributed into four groups (n = 4). Except for group 1 (G1), which received only PBS, the other three groups (G2, G3, and G4) were initially challenged with 10 μg of L. intermedia venom, diluted in 100 μL of NaCl 0.9%, by intradermic injection in the interscapular region. Thirty minutes after the challenge all groups were treated with secretome, except for group 2. Group 1 (G1-control group) received intradermal injection (ID) of 60 μg of secretome in 0.15 M PBS; Group 2 (G2) received 0.9% NaCl via ID; Group 3 (G3) received 60 μg of secretome, via ID and Group 4 (G4), received 60 μg of secretome by intravenous route. Rabbits were evaluated daily and after 15 days were euthanized, necropsied and skin samples around the necrotic lesions were collected for histological analysis. Results: Rabbits of G1 did not present edema, erythema, hemorrhagic halo, or necrosis. In animals from G2, G3, and G4, edema appeared after 6h. However, minor edema was observed in the animals of G2 and G3. Hemorrhagic halo was observed in animals, six hours and three days after, on G2, G3, and G4. Macroscopically, in G4, only one animal out of four had a lesion that evolved into a dermonecrotic wound. No changes were observed in the skin of the animals of G1, by microscopic evaluation. All animals challenged with L. intermedia venom showed similar alterations, such as necrosis and heterophilic infiltration. However, animals from G4 showed fibroblast activation, early development of connective tissue, neovascularization, and tissue re-epithelialization, indicating a more prominent healing process. Conclusion: These results suggest that secretome from mesenchymal stromal cells cultured in a xeno-free and human component-free culture media can be promising to treat dermonecrosis caused after Loxosceles spiders bite envenoming.

Background. The latex yield in Hevea brasiliensis trees is highly variable; Therefore, it is important to propagate commercial clones of this species by grafting in order to standardize or improve latex yields and therefore improve the economic income of producers in this part of the Amazon region. Objective. To evaluate the attachment and development of rubber clones propagated by grafting in the Peruvian jungle. Methodology. Nine-month-old patterns installed in the field were used. These were grafted with budding rods from the commercial clones TR-1, FX-3864, RRIM-600, IAN-873 and MDF-180. A completely randomized block design was used with five treatments and three blocks with 15 experimental units; each containing 30 repetitions. The data obtained were subjected to analysis of variance and Tukey's multiple range test (p

Summary: In this protocol, we describe how to perform the photo-isomerization of cyclic peptides containing an unsaturated β-amino acid. This process triggers the formation or disassembly of cyclic peptide nanotubes under appropriate light irradiation. Specifically, we start by describing the solid-phase synthesis of the cyclic peptide component. We also present a technique for performing isomerization studies in solution and how to extend it to microfluidic aqueous droplets.For complete details on the use and execution of this protocol, please refer to Vilela-Picos et al.1 : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

Green space exposure has been associated with improved mental, physical and general health. However, the underlying biological mechanisms remain largely unknown. The aim of this study was to investigate the association between green space exposure and cord and child blood DNA methylation.Data from eight European birth cohorts with a total of 2,988 newborns and 1,849 children were used. Two indicators of residential green space exposure were assessed: (i) surrounding greenness (satellite-based Normalized Difference Vegetation Index (NDVI) in buffers of 100 m and 300 m) and (ii) proximity to green space (having a green space ≥ 5,000 m2 within a distance of 300 m). For these indicators we assessed two exposure windows: (i) pregnancy, and (ii) the period from pregnancy to child blood DNA methylation assessment, named as cumulative exposure. DNA methylation was measured with the Illumina 450K or EPIC arrays. To identify differentially methylated positions (DMPs) we fitted robust linear regression models between pregnancy green space exposure and cord blood DNA methylation and between cumulative green space exposure and child blood DNA methylation. Two sensitivity analyses were conducted: (i) without adjusting for cellular composition, and (ii) adjusting for air pollution. Cohort results were combined through fixed-effect inverse variance weighted meta-analyses. Differentially methylated regions (DMRs) were identified from meta-analysed results using the Enmix-combp and DMRcate methods.There was no statistical evidence of pregnancy or cumulative exposures associating with any DMP (False Discovery Rate, FDR, p-value

Abstract The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people.

In this paper, a new fourth-order family of iterative schemes for solving nonlinear equations has been proposed. This class is parameter-dependent and its numerical performance depends on the value of this free parameter. For studying the stability of this class, the rational function resulting from applying the iterative expression to a low degree polynomial was analyzed. The dynamics of this rational function allowed us to better understand the performance of the iterative methods of the class. In addition, the critical points have been calculated and the parameter spaces and dynamical planes have been presented, in order to determine the regions with stable and unstable behavior. Finally, some parameter values within and outside the stability region were chosen. The performance of these methods in the numerical section have confirmed not only the theoretical order of convergence, but also their stability. Therefore, the robustness and wideness of the attraction basins have been deduced from these numerical tests, as well as comparisons with other existing methods of the same order of convergence.

This work proposes a high-efficiency High-Brightness LED (HB-LED) driver for Visible Light Communication (VLC) based on a Two-Input Buck (TIBuck) DC/DC converter. This solution not only outperforms previous approaches based on Buck DC/DC converters, but also simplifies previous proposals for VLC drivers that use the split power technique with two DC/DC converters: one is in charge of the communication tasks and the other controls the biasing of the HB-LED (i.e., lighting tasks). The real implementation of this scheme requires either two input voltage sources, one of which is isolated, or one DC/DC converter with galvanic isolation. The proposed implementation of splitting the power is based on a TIBuck DC/DC converter that avoids the isolation requirement, overcoming the major drawback of this technique, keeping high-efficiency and high communication capability thanks to the lower voltage stress both across the switches and at the switching node. This fact allows for the operation at very high frequency for communication purposes, minimizing switching power losses, achieving high efficiency and providing lower filtering effort. Moreover, the duty ratio range can also be adapted to the useful voltage range of the HB-LED load to maximize the resolution on the tracking of the output volage. The power is split by means of an auxiliary Buck DC/DC converter operating at low switching frequency, which generates the secondary voltage source needed by the TIBuck DC/DC converter. This defines a natural split of power by only processing the power delivered for communications purposes at high frequency. A 7 W output-power experimental prototype of the proposed VLC driver was built and tested. Based on the experimental results, the prototype achieved 94% efficiency, reproducing a 64-QAM digital modulation scheme and achieving a bit rate of 1.5 Mbps with error in communication of 12%.

The obtention of luminescent SiOxCy:H thin films deposited by the HW-CVD technique is reported here. We study the effect of different monomethyl-silane (MMS) flow rates on the films properties. An increase in the emission bandwidth and a red-shift was observed when the MMS flow increased. The luminescence was related to optical transitions in band tail states and with less contribution from quantum confinement effects. After, the films were annealed at 750 °C in nitrogen. The annealed film deposited at the highest MMS flow showed an emission spectrum like the as-deposited film, suggesting the same emission mechanisms. By contrast, the annealed film deposited at the lowest MMS flow showed two emission bands. These bands are due to the activation of radiative defects related to oxygen-deficient centers. MOS-like structures were fabricated as electroluminescent devices using the annealed films. Only the structure of the film with the highest carbon content showed light emission in a broad band in the visible spectrum region in forward bias, with a maximum centered close to 850 nm. The light emission mechanism was related to electron thermalization in the band tail states and a direct hole injection into deep states. The trap-assisted tunneling, Poole–Frenkel emissions and Fowler–Nordheim tunneling were proposed as the charge transport mechanism.

Epoxy resin composite matrices reinforced with carbon fibers are highly demanded by certain industries such as the aeronautics industry because of their exceptional mechanical properties. Unfortunately, the use of reinforcing carbon fibers makes these composite materials hard to recycle by conventional methods. Therefore, in this study, specific hydrothermal treatments have been employed to recover carbon fibers from the offcuts of composite parts from the aeronautics industry. The resin decomposition rates (DRs) achieved by different settings of the operating parameters, such as the use of alkaline catalysts (KOH, NaOH, or K2CO3), the application of mechanical stirring, the use of different reaction times, the solvent volume/composite mass ratio, the specific surface area (surface area/mass) of the composite pieces, and the operating temperature and pressure (subcritical or supercritical conditions), have been examined and assessed. Under the conditions that have been evaluated, resin decomposition rates nearly as high as 98% have been achieved, while the recycled fibers retained over 95% of their original tensile strength (TS).

This article introduces a novel two-step fifth-order Jacobian-free iterative method aimed at efficiently solving systems of nonlinear equations. The method leverages the benefits of Jacobian-free approaches, utilizing divided differences to circumvent the computationally intensive calculation of Jacobian matrices. This adaptation significantly reduces computational overhead and simplifies the implementation process while maintaining high convergence rates. We demonstrate that this method achieves fifth-order convergence under specific parameter settings, with broad applicability across various types of nonlinear systems. The effectiveness of the proposed method is validated through a series of numerical experiments that confirm its superior performance in terms of accuracy and computational efficiency compared to existing methods.

This paper offers a systematic review of the papers in the present century that have addressed the intersection between urbanism, universal accessibility, and the socio-educational sphere. The paper explores, describes, and interprets the published literature found in academic sources included in Scopus and Web of Science (WOS) from the year 2000 to the present about the intersection of these three topics. We start from the dialogue between the social and the educational spheres as a basic premise. Thus, the main objectives of this review are (1) to identify how many articles explicitly address the social dimension in relation to education and universal accessibility; (2) to determine if there is an upward or downward trend in socio-educational perspectives, inclusion, and new urbanism; and (3) to find out if the research provides frameworks for universal accessibility, urban planning, and socio-educational inclusion from this holistic perspective. After removing all exclusion criteria, the study was restricted to 29 papers. The small number of research found is noteworthy. We understand that this shortage is due to the inclusion of the social dimension as a required area. Although there seems to have been a slight increase in recent years, the sample found does not allow us to determine whether or not there is a greater interest in studying the social sphere in relation to inclusive education. We do conclude, however, that this gap highlights the need to make the socio-educational dimension more present.

ABSTRACT Introduction Vesicovaginal fistula (VVF) is the most common urogenital fistula due to iatrogenic cause, primarily associated with gynecologic surgery (1). Although both conservative and surgical management may be considered, the optimal treatment is still uncertain and several studies were published using different techniques (open, laparoscopic or robotic) and approaches (extravesical, transvesical or transvaginal) (2–5). In this context, we aim to report our initial experience repairing VVF with Single-Port (SP) Transvesical (TV) access. Materials and Methods Four patients with a diagnosis of VVF underwent SP-TV VVF repair between May 2022 and December 2023. Diagnosis was confirmed by cystoscopy, cystogram and in two cases by CT Urogram. Under general anesthesia, before robotic time, patients were placed in lithotomy position and a preliminary cystoscopy was performed. Fistula was noted and a 5fr stent was placed through the fistulous tract. Two ureteral stents were placed. Then, with patient supine, a transverse suprapubic 3cm incision and 2cm cystotomy were made for SP access. First step was to mark and remove fistula tract to the vagina. The edges of the vagina and bladder were dissected in order to have a closure free of tension and to create three different layers to close: vagina, muscularis layer of the bladder and mucosal layer of the bladder. A bladder catheter was placed, and the two ureteral stents were removed at the end of procedure. Results Mean age was 53 years old and three out of 4 patients developed VVF after gynecologic surgery. Two patients underwent VVF repair 6 and 8 months after total hysterectomy. One patient developed VVF after total hysterectomy and oophorectomy followed by radiation therapy. Last patient developed VVF after previous urological procedure. Fistula diameter was between 11 and 15mm. Operative time was 211 min, including preliminary cystoscopy, stents placement and SP-access. All patients were discharged on the same day with a bladder catheter, successfully removed between post-operative day 14-18 after negative cystogram. Only in one case a ureteral stent was left because the fistula was closed to the ureteral orifice and we reported one case of UTI twelve days after surgery, treated with outpatient antibiotics. Mean follow-up was 8 months, patients were scheduled for regular follow-up visits and no recurrence was reported. All patients have at least 3 months of post-operative follow-up. Conclusions Our experience suggests that SP Transvesical VVF repair may be considered as a safe and feasible minimally invasive treatment for small/medium fistulae (10-15mm).

John Henry Newman, Josemaría Escrivá, and Karol Wojtyła are three modern saints who insisted on the general or universal call to holiness in everyday life, which until recent centuries focused on religious vows, degrees of prayer or mystical experiences. All three taught that this call is rooted in the sacrament of baptism with its subsequent growth by means of prayer, sacramental life, and the exercise of the virtues. They conceived of Christian holiness in terms of the imitation of Christ through the action of the Holy Spirit. For them, each Christian participates in the threefold office of Christ, Priest, Prophet, and King. Their teaching on divine filiation, sanctification of work and secular realities is a notable contribution towards a theology of holiness which calls for further elaboration.

Abstract Background Compulsivity is the hallmark of addiction progression and, as a construct, has played an important role in unveiling the etiological pathways from learning mechanisms underlying addictive behavior to harms resulting from it. However, a sound use of the compulsivity construct in the field of behavioral addictions has been hindered to date by the lack of consensus regarding its definition and measurement. Here we capitalize on a previous systematic review and expert appraisal to develop a compulsivity scale for candidate behavioral addictions (the Granada Assessment for Cross-domain Compulsivity, GRACC). Methods The initial scale (GRACC90) consisted of 90 items comprising previously proposed operationalizations of compulsivity, and was validated in two panel samples of individuals regularly engaging in gambling and video gaming, using exploratory structural equation modeling (ESEM) and convergence analyses. Results The GRACC90 scale is unidimensional and structurally invariant across samples, and predicted severity of symptoms, lower quality of life, and negative affect, to similar degrees in the two samples. Additionally, poorer quality of life and negative affect were comparably predicted by compulsivity and by severity of symptoms. A shorter version of the scale (GRACC18) is proposed, based on selecting the 18 items with highest factor loadings. Conclusions Results support the proposal that core symptoms of behavioral addictions strongly overlap with compulsivity, and peripheral symptoms are not essential for their conceptualization. Further research should clarify the etiology of compulsive behavior, and whether pathways to compulsivity in behavioral addictions could be common or different across domains.

Abstract HIV-1 capsid (CA) stability is important for viral replication. E45A and P38A mutations enhance and reduce core stability, thus impairing infectivity. Second-site mutations R132T and T216I rescue infectivity. Capsid lattice stability was studied by solving seven crystal structures (in native background), including P38A, P38A/T216I, E45A, E45A/R132T CA, using molecular dynamics simulations of lattices, cryo-electron microscopy of assemblies, time-resolved imaging of uncoating, biophysical and biochemical characterization of assembly and stability. We report pronounced and subtle, short- and long-range rearrangements: (1) A38 destabilized hexamers by loosening interactions between flanking CA protomers in P38A but not P38A/T216I structures. (2) Two E45A structures showed unexpected stabilizing CANTD-CANTD inter-hexamer interactions, variable R18-ring pore sizes, and flipped N-terminal β-hairpin. (3) Altered conformations of E45Aa α9-helices compared to WT, E45A/R132T, WTPF74, WTNup153, and WTCPSF6 decreased PF74, CPSF6, and Nup153 binding, and was reversed in E45A/R132T. (4) An environmentally sensitive electrostatic repulsion between E45 and D51 affected lattice stability, flexibility, ion and water permeabilities, electrostatics, and recognition of host factors.

Summary: Background: Type 2 diabetes (T2D) susceptibility is influenced by genetic and environmental factors. Previous findings suggest DNA methylation as a potential mechanism in T2D pathogenesis and progression. Methods: We profiled DNA methylation in 248 blood samples from participants of European ancestry from 7 twin cohorts using a methylation sequencing platform targeting regulatory genomic regions encompassing 2,048,698 CpG sites. Findings: We find and replicate 3 previously unreported T2D differentially methylated CpG positions (T2D-DMPs) at FDR 5% in RGL3, NGB and OTX2, and 20 signals at FDR 25%, of which 14 replicated. Integrating genetic variation and T2D-discordant monozygotic twin analyses, we identify both genetic-based and genetic-independent T2D-DMPs. The signals annotate to genes with established GWAS and EWAS links to T2D and its complications, including blood pressure (RGL3) and eye disease (OTX2). Interpretation: The results help to improve our understanding of T2D disease pathogenesis and progression and may provide biomarkers for its complications. Funding: Funding acknowledgements for each cohort can be found in the Supplementary Note.

Background and aims: The presence of fungal infections has been described in patients after recovering from COVID-19. This study aims to conduct a systematic review of studies that reported fungal infections ( Mucor spp., Pneumocystis jirovecii , or Aspergillus spp.) in adults after recovering from COVID-19. Methods: We performed a systematic review through PubMed, Web of Science, OVID-Medline, Embase, and Scopus. The study selection process was performed independently and by at least two authors. We performed a risk of bias assessment using the Newcastle–Ottawa Scale for cohort and case–control studies, and the Joanna Briggs Institute’s Checklists for Case Series and Case Reports. Results: The systematic search found 33 studies meeting all inclusion criteria. There was a total population of 774 participants, ranging from 21 to 87 years. From them, 746 developed a fungal infection. In 19 studies, Mucor spp. was reported as the main mycosis. In 10 studies, P. jirovecii was reported as the main mycosis. In seven studies, Aspergillus spp. was reported as the main mycosis. Regarding the quality assessment, 12 studies were classified as low risk of bias and the remaining studies as high risk of bias. Conclusion: Patients’ clinical presentation and prognosis after recovering from COVID-19 with fungal infection differ from those reported patients with acute COVID-19 infection and those without COVID-19 infection.

Objective: We aimed to review the available evidence on the association between vitamin B12, folate, and homocysteine levels with worse outcomes among COVID-19 patients. Methods: The search was carried out in ten databases simultaneously run on 10 May 2023, without language restrictions. We included cross-sectional, case-control, and cohort studies. The random-effects meta-analysis was performed using the Sidik-Jonkman method and corrected 95% confidence intervals using the truncated Knapp-Hartung standard errors. Standardized mean difference and 95% CI was used as the measure effect size. Results: Thirteen articles were included in this review ( n = 2134). Patients with COVID-19 who did not survive had the highest serum vitamin B12 values (SMD: 1.05; 95% CI: 0.31–1.78; p = 0.01, I 2 = 91.22%). In contrast, low serum folate values were associated with patients with severe COVID-19 (SMD: −0.77; 95% CI: −1.35 to −0.19; p = 0.02, I 2 = 59.09%). The remaining tested differences did not yield significant results. Conclusion: Elevated serum levels of vitamin B12 were associated with higher mortality in patients with COVID-19. Severe cases of COVID-19 were associated with low serum folate levels. Future studies should incorporate a larger sample size.