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The mechanisms that work alongside BRAFV600E oncogene in melanoma development, in addition to ultraviolet (UV) radiation (UVR), are of great interest. Analysis of human melanoma tumors [data from The Cancer Genome Atlas (TCGA)] revealed that 50% or more of the samples expressed no or low amounts of serine/threonine protein kinase STK11 (also known as LKB1) protein. Here, we report that, in a mouse model, concomitant neonatal BrafV600E activation and Lkb1 tumor suppressor ablation in melanocytes led to full melanoma development. A single postnatal dose of UVB radiation had no effect on melanoma onset in Lkb1‐depleted mice compared with BrafV600E‐irradiated mice, but increased tumor multiplicity. In concordance with these findings and previous reports, Lkb1‐null irradiated mice exhibited deficient DNA damage repair (DDR). Histologically, tumors lacking Lkb1 were enriched in neural‐like tumor morphology. Genetic profiling and gene set enrichment analyses of tumor sample mutated genes indicated that loss of Lkb1 promoted the selection of altered genes associated with neural differentiation processes. Thus, these results suggest that the loss of Lkb1 cooperates with BrafV600E and UVR, impairing the DDR and increasing melanoma multiplicity and neural‐like dedifferentiation.

The renovation of buildings is key to the fight against climate change and offers opportunities to fix the population in rural areas, revalue their heritage and help decongest cities. In addition, it has a lower environmental impact than new construction. With this contribution, the energy study for the rehabilitation of the old Abbey of Salas de Bureba, located in the Caderechas Valley, north of Burgos, is presented. The aim is to return the building to its original state, so most of the facades will not be able to be insulated. A detailed energy simulation has been conducted and all viable options have been analysed, applying passive improvements combined with the installation of renewable energies. This project, whose implementation has already begun, has obtained a double A energy rating, which has allowed it to apply for aid from the PREE 5000 Programme.

Introduction: Since mechanical thrombectomy has allowed ischaemic stroke thrombus retrieval, the exhaustive study of this material has enabled better understanding of the potential physiopathological processes involved in thrombus formation. Development: Thrombotic pathways involved in the different vascular beds share common mechanisms, causing difficulties in the identification of specific patterns associated with stroke aetiology. However, other factors such as clot formation time, associated inflammatory status, or activation of additional immune and coagulation pathways (neutrophil extracellular trap [NET] delivery, platelet aggregation, endothelial activation, and von Willebrand Factor release) have been described as determinants in thrombus characteristics. Thus, variable proportions of fibrin-/platelet-rich and erythrocyte-rich areas are closely interrelated within the thrombus, frequently associated with a protective outer shell with high concentrations of fibrin, NETs, and von Willebrand Factor. The presence of these components, as well as their distribution and interrelationships, have been shown to have effects on the thrombus’ resistance to revascularisation treatments. Understanding of these pathways has enabled the development of adjuvant therapies capable of enhancing current fibrinolytic drugs and/or increasing the efficacy of endovascular treatments. Conclusion: Understanding of thrombus components and mechanisms involved in thrombus formation represent a potential pathway for the development of ischaemic stroke therapeutics with promising perspectives. Resumen: Introducción: La obtención del material trombótico en el ictus isquémico desde la generalización de la trombectomía mecánica ha permitido un estudio exhaustivo del mismo y de los posibles mecanismos fisiopatológicos subyacentes a su formación. Desarrollo: Los mecanismos trombóticos implicados en los diferentes lechos vasculares no difieren en exceso, condicionando una heterogeneidad importante que ha dificultado la identificación de patrones asociados al origen o etiología del ictus. Se ha observado sin embargo una mayor influencia de factores como el tiempo de desarrollo del coágulo, el estado inflamatorio sistémico o la activación de vías inmunes y de la coagulación [liberación de Neutrophil extracellular traps (NETs), agregación plaquetar, activación endotelial y liberación de Factor de vonWillebrand]. Como resultado, en el seno del trombo conviven en proporciones variables áreas ricas en eritrocitos y áreas ricas en plaquetas/fibrina con una íntima relación entre ellas y acompañadas con frecuencia de una coraza protectora con alto contenido en fibrina, Factor vonWillebrand y NETs. La presencia de estos componentes, así como su disposición e interrelación ha demostrado tener efectos en la resistencia a los diferentes tratamientos revascularizadores. El conocimiento de estas vías ha permitido el desarrollo de posibles terapias adyuvantes con capacidad de potenciar los tratamientos fibrinolíticos actuales y/o aumentar la eficacia del tratamiento endovascular. Conclusión: El conocimiento de los componentes del trombo y los posibles mecanismos implicados en su formación es una potencial vía de desarrollo en el tratamiento del ictus isquémico con resultados prometedores.

Abstract Background Homocysteine (Hcy) and the proprotein convertase subtilisin/kexin type 9 (PCSK9) significantly contribute to atherosclerosis (AS) as well as coronary lesion severity. Our previous work demonstrated that Hcy upregulates PCSK9, accelerating lipid accumulation and AS. A PCSK9 antagonist reduces plasma Hcy levels in ApoE−/− mice. These findings suggest complex roles for both Hcy and PCSK9 in AS. This study investigated the mutual mediating influence of Hcy together with PCSK9 on coronary lesion severity among individuals diagnosed with acute coronary syndrome (ACS), focusing on their interplay with inflammatory and lipid-related markers. Methods This cross-sectional study encompassed 617 individuals diagnosed with ACS. Baseline characteristics, including inflammatory and lipid-related markers, were compared between individuals with non-severe (SYNTAX score ≤ 22) and severe (SYNTAX score > 22) coronary lesions. To evaluate both the impacts of Hcy and PCSK9 on coronary lesions severity, multivariate logistic regression along with mediation analyses were utilized. The robustness of the findings was validated by conducting subgroup analyses and sensitivity tests. Results Patients with severe conditions showed higher levels of Hcy, PCSK9, and inflammatory markers compared to non-severe cases. Both Hcy and PCSK9 levels were independently linked to a heightened risk of severe coronary lesions(ORs: 1.03–1.04 and 1.01–1.02, respectively, all P

El estudio tiene como objetivo examinar qué factores resultan determinantes para la salida de la situación de sin techo en las personas sin hogar adultas, prestando especial atención a factores como la presencia de patología de salud mental (PSM) las características sociodemográficas y los itinerarios de atención utilizados. La metodología empleada está basada en un estudio pre-test y post test cuya muestra está compuesta por las personas atendidas en un centro de acogida para personas sin hogar durante los años 2019 y 2020 (N=241). La información utilizada se extrajo a partir de datos que correspondían al cuestionario de entrada, el cuestionario de salida y la información de caso, presente en la base de datos de la entidad, donde se registran los casos atendidos. A partir del análisis de los datos, se obtuvieron los siguientes resultados: los residentes con PSM atendidos mediante metodologías de abordaje integral parecen mostrar una probabilidad de salir con techo (ETHOS B o superior) del programa de atención similar a los residentes sin PSM. Entre los residentes con PSM, las estancias de más de 3 meses en el programa presentan mayor porcentaje de salidas con techo que los casos de menor temporalidad, o que no presentan PSM. Las personas con adicciones obtienen un porcentaje menor de salida con techo que las personas sin adicciones. El estudio concluye que para el caso de las personas sin hogar con patología de salud mental, resulta beneficioso para el éxito de la intervención, las estancias superiores a los 3 meses en el centro de acogida. Este resultado puede ser debido a que la citada temporalidad permite que sean atendidos por el servicio de salud mental, la adhesión a tratamiento, así como el acceso a ayudas públicas asociadas a la condición de salud que faciliten ingresos económicos y el acceso posterior a una vivienda o recursos residenciales finalistas. This study aimed to examine the factors that either mitigate or impede exiting from the roofless situation among single homeless adults who stayed in a homeless shelter. The study is focused on factors like mental disorder pathology, sociodemographic characteristics, as well as the itineraries taken by each resident. The methodology was based on pre-test post-test data, which was analysed by statistical tests. The study sample was composed by N=241 homeless adults who exit the housing program between 2019 and 2020. Data was collected from the entity’s database, where both baseline and exit questionnaires were digitally recorded for every participant in the program. The obtained results show that, on average, residents with mental health pathologies (MHP), that are treated through a comprehensive approach, seem to show similar results in terms of housing outputs (not roofless, ETHOS=B or higher) in comparison with residents without mental health pathologies. Among residents with MHP, staying for more than 3 months in the program has a higher percentage of exits out of the roofless situation than those cases that have a shorter duration (less than 3 months), or those who do not have any MHP. People with addictions show lower percentages of exiting the roofless situation compared to people without addictions. The study concludes that, for homeless people with MHP, stays longer than 3 months in a service for homeless people are beneficial for the success of the program, in terms of housing situation. Within this period, they have more chances to be attended by the mental health service, allowing them to adhere to the prescribed treatments. This period may allow them to access to public aids associated to their health condition, which improves their economic situation, their access to housing or access to permanent residential resources.

Masquerading bundle branch block (MBBB) is a rare presentation of bifascicular blocks. It is the result of a right bundle branch block associated with an advanced left anterior fascicular block due to extensive damage to the conduction system. We present the case of a 75-year-old male with late onset presentation anterior wall myocardial infarction (MI) with ongoing ischemia (which evolved into a ventricular septal defect [VSD]). Electrocardiographically, the MBBB is characterized by a prominent R in V1, left axis deviation and absence of small S waves in I and aVL. Its presence confers a poor prognosis and high risk of progressing to advanced atrioventricular block (AAVB). A mortality rate between 18% and 38.9% has been found and 41.4%–59% of the patients develop AAVB requiring pacemaker implantation. To our knowledge, this is the first reported MBBB case in the setting of an MI complicated with VSD, demonstrating its association with the presence of critical anteroseptal ischemia. The patient rejected any kind of intervention, palliative care was offered, and he died 2 months later.

Purpose: Non-obstructive azoospermia (NOA) is a common, but complex problem, with multiple therapeutic options and a lack of clear guidelines. Hence, there is considerable controversy and marked variation in the management of NOA. This survey evaluates contemporary global practices related to medical and surgical management for patients with NOA. Materials and Methods: A 56-question online survey covering various aspects of the evaluation and management of NOA was sent to specialists around the globe. This paper analyzes the results of the second half of the survey dealing with the management of NOA. Results have been compared to current guidelines, and expert recommendations have been provided using a Delphi process. Results: Participants from 49 countries submitted 336 valid responses. Hormonal therapy for 3 to 6 months was suggested before surgical sperm retrieval (SSR) by 29.6% and 23.6% of participants for normogonadotropic hypogonadism and hypergonadotropic hypogonadism respectively. The SSR rate was reported as 50.0% by 26.0% to 50.0% of participants. Interestingly, 46.0% reported successful SSR in

Landslides represent a serious mountain hazard to lives and infrastructure, especially when geological factors such as highly fractured rocks, faulting, steep topography, and weathering combine with seismic triggering factors. Considering the potential of producing outcomes, we study the Chuquibamba rotational landslide that runs along the NW-SE Incapuquio-Challaviento fault system in southernmost Peru. Its elongated U-shaped and polylobate crown scarp is typical of fault-related landslides, and it is carved into the ignimbrites of the Chuquibamba Formation. The geomorphology of the failure and its associated deposit define seventeen coalescing rotational slides and a widespread debris avalanche. This deposit, the main topic of this study, dated at ca. 102 Å} 5 ka using 10Be (from previous works), is confined to the lower parts of the Grande River valley. It is exposed for about 22.5 km from 3,900 to 1,167 masl with its main front located at ~ 10 km upstream of the Majes River. It covers an area of 33.64 km2 with a minimum volume of 0.72 km3. The resulting deposit has an H/L = 0.12, which is typical of dry debris avalanches elsewhere. It consists of block and matrix facies that have different textural and granulometric features. At the time of its emplacement, the moving avalanche overpassed 20 and 12 m-high obstacles, attaining minimum speeds of 20 and 15 m/s at distances of 15 and 20 km from the source, respectively. After the landslide emplacement, the debris avalanche was re-mobilized by intense rains that produced debris flows, as attested by outcrops along the extension of the debris avalanche and beyond its front. All the features of the Chuquibamba dry avalanche, along with modern seismicity and the intersection of active faults in the region, suggest that the failure had a tectonic origin (uplift and movement along faults) instead of deglaciation, extraordinary rain, or extreme rock weathering. Therefore, landslide generation is a potential hazard in this area of Peru.

El objetivo de este estudio es desarrollar un diseño final para el Talud Noroeste de la Mina Cuajone (Perú) utilizando el cálculo del factor de seguridad (FS) mediante métodos de elementos finitos, planteando que este método permite una evaluación más precisa de la estabilidad del talud. La metodología incluyo la caracterización geológica y geotécnica del talud mediante mapeo de campo, análisis de muestras y pruebas de laboratorio. Se creo un modelo tridimensional usando el software Phase2 para simular la interacción entre la geometría del talud y las condiciones operativas, realizando un análisis de estabilidad bajo diferentes cargas y perturbaciones. Los resultados indican que el método de elementos finitos proporciono una evaluación detallada del factor de seguridad y del ángulo interrampa (IRA). En la zona sur (sección A-A'), se determina que un IRA de 43° genera un FS de 1.1. En la zona norte (sección B-B'), se recomienda un IRA de 38° para lograr un FS de 1.57. Los hallazgos son fundamentales para garantizar la seguridad y eficiencia operativa en la mina, ya que un diseño de talud inadecuado podría comprometer la integridad de la infraestructura y la seguridad de los trabajadores. La aplicación de métodos avanzados como el análisis de elementos finitos y la consideración de factores como el IRA y el factor de perturbación permite una evaluación precisa de la estabilidad del talud y la implementación de medidas de estabilización efectivas para gestionar los riesgos y desarrollar soluciones de refuerzo específicas según la configuración geotécnica del talud.

Abstract A well-balanced ion channel trafficking machinery is paramount for the normal electromechanical function of the heart. Ion channel variants and many drugs can alter the cardiac action potential and lead to arrhythmias by interfering with mechanisms like ion channel synthesis, trafficking, gating, permeation, and recycling. A case in point is the Long QT syndrome (LQTS), a highly arrhythmogenic disease characterized by an abnormally prolonged QT interval on ECG produced by variants and drugs that interfere with the action potential. Disruption of ion channel trafficking is one of the main sources of LQTS. We review some molecular pathways and mechanisms involved in cardiac ion channel trafficking. We highlight the importance of channelosomes and other macromolecular complexes in helping to maintain normal cardiac electrical function, and the defects that prolong the QT interval as a consequence of variants or the effect of drugs. We examine the concept of “interactome mapping” and illustrate by example the multiple protein–protein interactions an ion channel may undergo throughout its lifetime. We also comment on how mapping the interactomes of the different cardiac ion channels may help advance research into LQTS and other cardiac diseases. Finally, we discuss how using human induced pluripotent stem cell technology to model ion channel trafficking and its defects may help accelerate drug discovery toward preventing life-threatening arrhythmias. Advancements in understanding ion channel trafficking and channelosome complexities are needed to find novel therapeutic targets, predict drug interactions, and enhance the overall management and treatment of LQTS patients.

Due to the rapid development of power electronics and energy storage technologies, the trend toward electrified railway systems with onboard energy storage systems (OESS) is being followed by main train manufactures. In such systems, the control of the dc-link can be critical for stability and optimal power sharing between different energy sources. This paper presents a dc-link control strategy intended for OESS-based traction chains. A distinguishing characteristic of the proposed method is its ability to smoothly share the power demand among the available power sources, including the kinetic energy of the train, based on predefined priority levels. The control smoothly reacts to changes in the power limits, including no power, of the available energy sources, without modifying the control structure and with negligible variations of dc-link voltage. Simulation results are provided using a real train model with an onboard battery system. Finally, the proposed control is validated on a hardware prototype.

Background: Overview of the literature: Idiopathic scoliosis (IS) is most commonly developed during adolescence and affects 2%–3% of the population. The overall complication rate for corrective surgeries in adolescent IS patients is described as 6.3%. Perioperative complications include intraoperative blood loss, neurological deficit, and infection, with excessive blood loss being one of the most common. The aim of the study is to evaluate the prevalence of major and minor complications following posterior or anterior fusion for IS. Methods: Retrospective multicenter study of data from the DWG-Register of patients who underwent operative treatment for IS from January 2017 to September 2022. Inclusion criteria: IS, age between 10 and 30 years. Results: In total, 825 IS patients undergoing fusion were identified in the registry; n = 801 (Group 1) did not have operative complications and n = 24 had a complication related to surgical procedure (Group 2); therefore, the complications rate was 2.9%. A 1.3% rate of major complications and 1.6% rate of minor complications were recorded as follows: spinal cord damage n = 2 (8.4%), subfaszial hematoma n = 2 (8.4%), motor dysfunction n = 1 (4.2%), cerebrospinal fluid (CSF)-leakage n = 7 (29.2%), sensory dysfunction n = 6 (25%), bowel/bladder dysfunction n = 1 (4.2%), superficial site infection n = 2 (8.4%), and pulmonary lung atelectasis n = 3 (12.5%). According to the logistic regression model, an odds ratio for pedicel screws versus laminar hooks for hyperkyphosis correction of 3.73 and for Ponte-osteotomy of 11.5 was found. Conclusions: In IS patients treated operatively, the prevalence of nonneurologic postoperative complications following corrective surgery was 1.80% with CSF leak being the leading risk of complication at 0.84.%. These findings should guide surgeons in their intraoperative Dural tear repair particularly osteotomies. Alternate level pedicle-screw placement with laminar hooks leads to higher operation time and more extensive fusion with consequent slightly prevalence in perioperative complications.

Background: Intramedullary tumors represent only 10% of the spectrum of spinal tumors. Their management is not an easy task and depends essentially on the surgical resection which can be very challenging. The main aim of our study was to analyze the complication rate in intramedullary tumors as well as postoperative outcome after intramedullary tumor resection. Methods: This was a retrospective analysis of data from the “DWG-Register” of patients who have undergone operative treatment for primary intramedullary tumors in 170 departments from January 2017 to May 2021. Since 2017, pre-, intra-, and postoperative data until demission from the hospital have been continually collected in the “DWG-Register” (a total of 179,955 in a period of 4 years in 170 departments). Results: In total, 307 primary intramedullary tumors in the spine were identified; n = 248 (Group 1) had nonoperative complications and n = 59 had a complication related to the surgical procedure (Group 2); taking this in to account, die complication rate was 19.2%. The incidence of complications was: epidural hematoma n = 5 (8.4%), paresis n = 23 (38.9%), bowel/bladder dysfunction n = 15 (25.4%), wound infection n = 5 (8.4%), medullary injury n = 2 (3.4%), cerebrospinal fluid (CSF) leakage n = 15 (25.4%), and reintervention with hematoma, abscess, or surgical CSF leakage management in n = 22 (37.2%). The risk of permanent morbidity increased with a thoracic level, masculine gender, a long clinical history, presence of epidural hemorrhage, blood transfusion, and surgery on a recurrent tumor. Conclusion: Medullary tumors are a rare entity with a relative high complication rate (20%). Improvement of symptoms postoperative depends on several factors such as operated level, masculine gender, a long clinical history, presence of epidural hemorrhage, blood transfusion, and surgery on a recurrent tumor. In rare pathologies such as intramedullary tumors, the data from the DWG Register can be used to describe spinal surgery care in “real life.”

Introducción. La artritis psoriásica es una enfermedad compleja y los antígenos leucocitarios humanos (Human Leukocyte Antigen, HLA) son un factor clave en el desarrollo de la enfermedad. En Latinoamérica, hay pocos datos sobre dichos antígenos en pacientes con artritis psoriásica. Objetivo. Describir la frecuencia de genotipos, alelos y haplotipos de los antígenos leucocitarios humanos en casos de artritis psoriásica y asociarlos con variables clínicas. Materiales y métodos. Se desarrolló un estudio retrospectivo del 2012 al 2023 en el que se evaluaron los adultos con artritis psoriásica según los criterios CASPAR. Se incluyeron controles sanos con HLA-A, B, C y DR tipificados por PCR/SSO en un dispositivo Luminex 100/200 xMAP™. Se hizo un análisis comparativo entre los datos de los antígenos leucocitarios de los pacientes y los de los controles sanos. Resultados. Se incluyeron 401 controles sanos y 37 pacientes con artritis psoriásica, entre los cuales se identificaron 46 genotipos, 75 alelos y 32 haplotipos. Los HLA más frecuentes fueron HLA-A*24 (37,1 %), HLA-B*35 (20,8 %), HLA-C*03 y HLA-C*07 (cada uno con el 19,9 %) y HLA-DR*04 (30 %). Al comparar su frecuencia con la de los controles sanos, la frecuencia genotípica fue menor para HLA-A*02, HLA-A*11, HLA-B*35, HLA-DR*01, HLA-DR*07, HLA-DR*13 y HLA-DR*15 (p < 0,05), lo que significa que, si bien el HLA-B*35 fue frecuente en la artritis psoriásica, su frecuencia fue menor al compararse con la de los controles. La frecuencia de HLA-A*24 y HLA-B*44 fue diferente en los pacientes con compromiso cutáneo (p < 0,05); la de HLA-B*40 y HLA-B*35 en aquellos con compromiso articular (p < 0,05), y la de HLA-A*26 y HLA-C*16 en aquellos con manifestaciones extraarticulares (p < 0,05). La frecuencia alélica de HLA-A*26:01 y HLA-C*16:01 en los casos con manifestaciones extraarticulares, fue también significativa. La frecuencia de HLA-Cw*6 fue 6,7 % y la ausencia de HLA-B*27 en nuestra población es uno de los aspectos por destacar. Conclusiones. En el análisis de HLA en artritis psoriásica se encontrótró una poca frecuencia de HLA-C*06 y ausencia de HLA-B*27. Este hallazgo es diferencial respecto a la población caucásica. Estos resultados revelaron otros alelos de interés, algunos relacionados con variables clínicas. Las diferencias encontradas podrían estar relacionadas con la mezcla racial de nuestra población.

Inborn errors of immunity are monogenic disorders that predispose patients to immune dysregulation, autoimmunity, and infection. Some autoimmune diseases, such as autoimmune cytopenias, systemic lupus erythematosus, and inflammatory bowel diseases, are increasingly recognized as phenotypes of inborn errors of immunity. The objective of this article was to identify red flags or clinical/laboratory markers to suspect inborn errors of immunity in patients with autoimmune cytopenias, systemic lupus erythematosus, and inflammatory bowel diseases through a systematic literature review. The study followed the systematic reviews and meta-analysis guidelines (PRISMA). After selection, we included 36 articles, and their methodological quality was verified using the Joanna Briggs Institute tools for individual risk of bias analysis. The principal red flags in autoimmune cytopenias are chronic, recurrent, and refractory cytopenias, recurrent infection, severe infectious complications associated with immunosuppressive treatment, and chronic lymphoproliferation. In systemic lupus erythematosus, red flags include age of onset before five years, severe organ involvement, chilblain lesions, and chronic lymphoproliferation. For inflammatory bowel diseases, red flags are an age of onset before two years, resistance to conventional therapies, atypical endoscopic or histologic findings, and consanguineous parents. Autoimmune diseases may be the primary manifestation of inborn errors of immunity in pediatric and adult patients. An early diagnosis of a monogenic disorder allows for the tailoring of effective treatment plans, providing prognostic information to families, and offering genetic counseling.

Objetivo: Comunicar los resultados de la reconstrucción del complejo del fibrocartílago triangular en las lesiones crónicas Atzei 4, mediante la ligamentoplastia de Carratalá con injerto de palmar menor. Materiales y Métodos: Se evaluó, en forma retrospectiva, a 9 pacientes (6 hombres y 3 mujeres) con lesión del complejo del fibrocartílago triangular Atzei 4. Todas las lesiones se reconstruyeron con artroscopia mediante un injerto libre del palmar menor con fijación radial y cubital usando la técnica de Carratalá. Se analizaron los rangos de movilidad, la fuerza de agarre y se emplearon la escala MWS y el cuestionario DASH. Resultados: Las pruebas de dolor y la fuerza mejoraron en los 9 pacientes, en un seguimiento promedio de 14 meses. Todos trabajaban. El rango de movilidad promedio fue de 80° de extensión, 80° de flexión y 160° de pronosupinación. El puntaje de la escala MWS fue excelente en el 78%, bueno en el 11% y malo en el 11%. El puntaje DASH promedio antes de la cirugía era de 61 y fue de 9 a los 14 meses de la intervención. El promedio de la fuerza comparativa contralateral fue del 85%. Conclusiones: La reconstrucción artroscópica del complejo del fibrocartílago triangular en lesiones crónicas Atzei 4, mediante la ligamentoplastia de Carratalá para la estabilización radiocubital distal, es una variante artroscópica mínimamente invasiva, replicable con buenos resultados funcionales.

Objetivo: Evaluar, en forma retrospectiva, la función y los resultados de los pacientes con una lesión foveal del complejo del fibrocartílago triangular tratados con un anclaje óseo isométrico con doble sutura ligamentaria, monotúnel, por vía artroscópica. Materiales y Métodos: Se evaluó a 14 pacientes consecutivos, en edad laboral, que tenían una lesión foveal del complejo del fibrocartílago triangular Atzei 2/3 y un seguimiento promedio de 15 meses. Todas las lesiones se repararon mediante artroscopia con una doble sutura ligamentaria, isométrica, sin nudo con anclaje foveal monotúnel. Se utilizó una sutura para fijar el ligamento radiocubital volar y otra para fijar el ligamento radiocubital dorsal a la fóvea. Se evaluaron el rango de movilidad, la fuerza de agarre, y se utilizaron la escala MWS y el puntaje DASH. Resultados: Los puntajes de dolor y fuerza mejoraron. El puntaje de la escala MWS fue excelente y bueno. El puntaje DASH preoperatorio era de 62 y de 8 en el posoperatorio. El promedio de la fuerza comparativa contralateral fue del 80%. Conclusiones: La reparación artroscópica de las lesiones Atzei 2/3 mediante doble sutura isométrica con anclaje ligamentario monotúnel, sin nudo logra buenos resultados: mejora el rango de movilidad, recupera la estabilidad y la fuerza en forma total o parcial. Se debe tener cuidado en el pasaje de las suturas por el complejo del fibrocartílago triangular y la fijación mediante el tornillo en la metáfisis para evitar las complicaciones comunicadas en esta serie.

Objetivos: Presentar una técnica artroscópica para el tratamiento de la artrosis radiocubital distal que consiste en la interposición de un cilindro de poliéster tejido y de palmar menor, y los resultados preliminares. Materiales y Métodos: Se analizaron, en forma retrospectiva, los resultados de esta técnica en 5 pacientes con artrosis radiocubital distal clasificada clínicamente y por vía artroscópica, en un seguimiento promedio de 11 meses. Todas las lesiones se repararon por vía artroscópica mediante una técnica de autor denominada técnica de interposición en parapente. Se evaluaron los rangos de movilidad, la fuerza de agarre con la escala MWS y el cuestionario DASH. Resultados: Se incluyó a 5 pacientes (4 artrosis secundarias y 1 artrosis primaria). Los resultados de las pruebas de dolor y fuerza mejoraron. El rango de movilidad promedio fue: 75° de pronación, 70° de supinación, 80° de extensión y 70° de flexión. Los resultados, según la escala MWS, fueron excelentes (83%) y buenos (17%), no hubo resultados malos. El puntaje promedio del cuestionario DASH era 56 antes de la cirugía y 20 en el posoperatorio. El promedio de la fuerza comparativa contralateral fue del 70%. Conclusiones: La técnica de interposición artroscópica en parapente propone ser una alternativa a las técnicas de salvataje articular utilizadas hoy, ya que es mínimamente invasiva, conserva estructuras de las partes blandas, es reproducible, permite la estabilización de la articulación radiocubital distal y evita el pinzamiento radiocubital proximal.

Abstract This study expands upon a technique our team previously developed for generating nanobubbles on demand with a collimated pulsed laser beam. This work highlights how the controlled addition of gold nanoparticles enhances nanobubble generation efficiency in water, even at laser intensities well below the threshold for multiphoton ionization. Specifically, we investigated the influence of nanoparticles of three distinct sizes on the laser fluence threshold for bubble nucleation and the lifetime of the resultant nanobubbles. Our findings confirm that nanoparticles with a diameter of 60 nm exhibit the greatest nucleation efficiency, achieving nearly 45 % at a fluence threshold of around $$70\,(\pm \,11)\,\hbox {mJ/cm}^2$$ . Interestingly, nanoparticle size did not impact the nanobubble lifetime.

El objetivo de este trabajo es analizar las presencias y ausencias de la materialidad arqueológica en las representaciones cartográficas de un sector de la comunidad de Puerta de San José (Belén, Catamarca). Para ello, se realizó un ejercicio de mapeo colectivo en escuelas secundarias de la región en el marco de una práctica de campo, a cargo de estudiantes de la carrera de Antropología de la Universidad Nacional de La Plata durante el viaje de campaña de la cátedra de Arqueología Americana II en septiembre de 2022. En los mapas revisados se observa la ausencia de representaciones de la materialidad arqueológica que posee la zona, que invitan a reflexionar sobre los posibles motivos, conscientes o no, por los cuales no fue representada por les estudiantes locales. Así, se Brinda un ejemplo de la utilidad de la cartografía social como herramienta para abordar distintas problemáticas acerca del vínculo entre las sociedades y el patrimonio arqueológico.

Background: Idiopathic pulmonary fibrosis (IPF) is a chronic, disabling disorder of unknown etiology, poor prognosis, and limited therapeutic options. Previously, 3′5-dimaleamylbenzoic acid (3′5-DMBA) was shown to exert resolving effects in IPF, offering a promising alternative for treating this disease; however, the molecular mechanisms associated with this effect have not been explored. Objetive: We evaluated the potential antifibrotic mechanisms of 3′5-DMBA by network pharmacology (NP) and molecular docking (MD). Methods: 3′5-DMBA-associated targets were identified by screening in SwissTargetPrediction. IPF-associated targets were identified using lung tissue meta-analysis and public databases. Common targets were identified, and a protein–protein interaction (PPI) network was constructed; we ranked the proteins in the PPI network by topological analysis. MD validated the binding of 3′5-DMBA to the main therapeutic targets. Results: A total of 57 common targets were identified between 3′5-DMBA and IPF; caspase 8, 9, 3, and 7; myeloid leukemia-induced cell differentiation protein Mcl-1; and poly [ADP-ribose] polymerase 1 are primary targets regulating PPI networks. Functional analysis revealed that the common targets are involved in the pathological features of tissue fibrosis and primarily in the apoptotic process. MD revealed favorable interaction energies among the three main targets regulating PPI networks. Conclusions: NP results suggest that the antifibrotic effect of 3′5-DMBA is due to its regulation of the pathological features of IPF, mainly by modulating signaling pathways leading to apoptosis, suggesting its therapeutic potential to treat this disease.

Large quantities of seeds are generated and discarded during agro-industrial mango processing. However, mango seeds still contain valuable components such as starch, which has applications in various industries. This study aimed to obtain and characterize starches from the seeds of five mango cultivars (Ataulfo, Manililla, Piña, Tapana, and Tommy Atkins). The isolated starches were evaluated for their physicochemical, morphological, structural, thermal, and rheological characteristics. The starches showed creamy white colorations, and their granules had spherical and oval shapes. This starch source contains a high percentage of apparent amylose, greatly influencing its thermal, rheological, and functional properties. Structural and molecular studies showed that all starches presented an A-type X-ray diffraction pattern, impacting their water absorption and viscosity. The transition temperatures were relatively high, which could be influenced by the length of the amylopectin chains and their intermediate components, the apparent amylose content, and other components such as lipids and anomalous amylopectin. The starches evaluated behaved as pseudoplastic materials, while oscillatory tests revealed that the pastes formed with mango starches are more elastic than viscous. In conclusion, research on the seed starch properties of different mango cultivars provides interesting results for their potential application in foods. It could contribute to the value-added processing of mango seeds as a potential starch source.

Abstract Background The satisfaction of patients with sedation by nursing staff is an issue of interest for the quality of health care, influencing the recovery and well-being of patients as well as their confidence in and adherence to treatment. One of the most frequently performed diagnostic and therapeutic tests requiring sedation are digestive endoscopies, so it would be interesting to study satisfaction in these services. Aim To determine the level of patient satisfaction and safety with sedation via digestive endoscopies by nurses. Methods This was a cross-sectional study in the Digestive Endoscopy Service at the University Hospital of Toledo, Spain. The sample consisted of 660 adult patients from the digestive endoscopy service who were sedated between June–September 2023. The degree of satisfaction with the service was measured by the questionnaire: Survey of patient satisfaction with the digestive endoscopy service. The study was approved by the ethics committee. Results Patients who reported satisfaction with the treatment were very satisfied with the sedation provided by the nurses. The most valued item was the attention of the nursing professionals. The least valued items were the waiting time for the appointment and the time spent in the waiting room on the same day. The incidence of complications recorded during the test were minimal (2% of all patients). Conclusions Most patients are satisfied with the sedation administered by nurses via digestive endoscopies, and complications were rare, supporting the efficacy and acceptance of this practice. Clinical practice guidelines and consensus documents in Spain guarantee that nurses have autonomy to administer sedation in digestive endoscopy services, but there is a lack of national regulations to support this technique. The current consensus in Spain is that specific training is necessary for such nurses.

Summary The house sparrow (Passer domesticus) is a gregarious generalist species, which makes it a good model for studying play. However, play has not been described for this species so far. We describe play behaviour in house sparrows for the first time, quantifying all play and play-related behaviours, searching for differences between the different sexes and ages, the possible association with reproductive success and the diffusion of this behaviour in the population. All behaviours were recorded from the end of 2018 breeding season to the start of the new one in 2019. Behaviours were classified into four levels of interaction of increasing complexity and intensity. Results showed that play behaviour was restricted to the breeding season, adult males played more often than the rest of the groups, and their behaviours correlated with the number of recruits they produced. Moreover, “Maximum Level” of play of the mothers significantly and positively correlated with that of their offspring, and the “Maximum Level” of an individual with the proportion of playing siblings. Despite the limitations of the present study, our results point out the existence of benefits for the reproductive success of playing individuals.

Abstract This research investigates the concentrations, sources, and health risks of polycyclic aromatic hydrocarbons (PAHs) and nitrated PAHs (NPAHs) in particulate matter with an aerodynamic diameter of 10 $$\mu$$ m or less (PM $$_{10}$$ ) from critical urban centers in northern Mexico: Metropolitan Monterrey Area (MMA), Chihuahua (CHI), and Ciudad Juárez (CDJ). Advanced gas chromatography-mass spectrometry (GC-MS and GC-NCI-MS) revealed significant PAHs concentrations, with levels in MMA reaching 108.89 ± 99.90 ng/m $$^3$$ , CHI at 100.69 ± 122.60 ng/m $$^3$$ and CDJ at 73.26 ± 90.85 ng/m $$^3$$ . Significantly, 3-nitrofluoranthene (3N-FLA) and 1-nitropyrene (1N-PYR), known for their potent toxicity, were among the most prominent NPAHs, with total concentrations in MMA, CHI, and CDJ at 470.32 pg/m $$^3$$ , 247.26 pg/m $$^3$$ , and 193.20 pg/m $$^3$$ , respectively. Source apportionment using diagnostic ratios (DRs) and principal component analysis (PCA) indicated that biomass burning, vehicular emissions, and industrial activities were the primary sources of MMA. At the same time, CHI and CDJ were influenced more by industrial and diesel emissions. Health risk assessments based on benzo[a]pyrene equivalent (BaPeq) concentrations and excess cancer risk (ECR) demonstrated moderate to significant cancer risks, with CDJ exhibiting the highest NPAHs-related risk. This study makes several significant contributions: it presents the first analysis of PAHs and NPAHs levels in these urban areas, identifies key emission sources, and quantifies associated health risks, providing essential data for developing targeted public health policies and environmental regulations.

DC-DC Interleaved Boost Converter (DC-DC IBC) topology was developed through the interleaving technique since conventional DC-DC Boost Converter has many problems related to complex circuit control, harmonics, and output power. In this research, DC-DC IBC was developed into a Two-Phase AC-AC Interleaved Boost Converter (TP AC-AC IBC), then combined with a Two-Phase Full Bridge Inverter to become a Two-Phase DC-AC Interleaved Boost Inverter (TP DC-AC IBI). TP DC-AC IBI has several advantages, including minimal current and voltage ripples and greater output power because it consists of two AC-AC IBCs. This research aims to meet highly regulated AC voltage needs with the renewable energy source input using the proposed topology, by implementing Proportional Integral (PI) close loop control system. The output voltage is detected using a voltage transducer LV-25P, then compared with a reference voltage and controlled using a PI controller to keep the output voltage consistently stable. The switching signal setting uses the Sinusoidal Pulse Width Modulation (SPWM) technique by modulating the control output with a high frequency. As a verification step, testing was carried out using Power Simulator (PSIM) software and then validated by hardware testing in the laboratory. Testing was carried out using several test signals, and it was found that the proposed method worked well. System efficiency and Total Harmonic Distortion (THD) tests carried out using various load values, and a maximum efficiency of 93.87% and a minimum THD of 2.46% were obtained.

Abstract Myocarditis is a serious cardiovascular ailment that can lead to severe consequences if not promptly treated. It is triggered by viral infections and presents symptoms such as chest pain and heart dysfunction. Early detection is crucial for successful treatment, and cardiac magnetic resonance imaging (CMR) is a valuable tool for identifying this condition. However, the detection of myocarditis using CMR images can be challenging due to low contrast, variable noise, and the presence of multiple high CMR slices per patient. To overcome these challenges, the approach proposed incorporates advanced techniques such as convolutional neural networks (CNNs), an improved differential evolution (DE) algorithm for pre‐training, and a reinforcement learning (RL)‐based model for training. Developing this method presented a significant challenge due to the imbalanced classification of the Z‐Alizadeh Sani myocarditis dataset from Omid Hospital in Tehran. To address this, the training process is framed as a sequential decision‐making process, where the agent receives higher rewards/penalties for correctly/incorrectly classifying the minority/majority class. Additionally, the authors suggest an enhanced DE algorithm to initiate the backpropagation (BP) process, overcoming the initialisation sensitivity issue of gradient‐based methods like back‐propagation during the training phase. The effectiveness of the proposed model in diagnosing myocarditis is demonstrated through experimental results based on standard performance metrics. Overall, this method shows promise in expediting the triage of CMR images for automatic screening, facilitating early detection and successful treatment of myocarditis.

Background: Persistence of a low CD4/CD8 ratio is associated with an increased morbimortality in people living with HIV (PLWH) under effective antiretroviral therapy. We aimed to explore the immunological significance of a persistently low CD4/CD8 ratio, even despite normal CD4 levels, and assess whether these features vary from those associated to a low nadir-CD4, another well-established predictor of disease progression. Methods: CD4-recovered PLWH were classified by CD4/CD8 ratio after three-years of ART (viral suppression, CD4≥500; R 1.2, n = 28). sj/β-TRECs ratio and inflammatory-related markers were quantified. PBMCs were immunophenotyped by CyTOF and functionally characterized by ELISPOT. Subjects were also reclassified depending on nadir-CD4 (N ≤ 350/N > 350). Results: R 1.2 (increased β2-microglobulin, D-dimers and IP-10 before ART). R 350, the main features were altered functional markers in CD4 T-cells, despite no differences in maturational subsets, together with a restricted T-cell cytokine secretion pattern. Conclusion: Persistence of low CD4/CD8 ratio in successfully-treated PLWH, with normal CD4 counts, is associated with baseline inflammation and low thymic function, and it features post-therapy alterations specific to CD8 T-cells. Differently, subjects recovered from low nadir-CD4 in this setting feature post-therapy alterations on CD4 T-cells. Hence, different mechanisms of disease progression could underlie these biomarkers, potentially requiring different clinical approaches.

Objetivo. Describir las experiencias de la Comisión Nacional Asesora de Eventos Supuestamente Atribuibles a la Vacunación o Inmunización (ESAVI) graves implementada en Ecuador en el período 2020-2023. Método. Se realizó un informe que analiza la implementación, el funcionamiento y los resultados de la Comisión Nacional Asesora sobre ESAVI graves en Ecuador. Se realizó un análisis cuantitativo de los registros de vacunación y un análisis cualitativo con base en testimonios de expertos, que recoge las experiencias directas y desafíos operacionales enfrentados por los miembros de la Comisión. Resultados. La implementación de la Comisión ha permitido el registro y el análisis sistemático de los ESAVI graves. De 256 casos notificados, se analizaron 139; 59% como eventos coincidentes; 16,6% no clasificables; 6,5% indeterminados; 5% como eventos por estrés; 3,6% como eventos relacionados con un error programático, y 9,4% relacionados con la vacuna, que incluyeron alergias, síndrome de Guillain-Barré y trombosis, entre otros. Los testimonios de los expertos destacaron la necesidad de mejorar la capacitación del personal y la infraestructura tecnológica, y compartieron que la Comisión desempeñó un papel crucial en la vigilancia de la seguridad de las vacunas, además de incrementar la confianza de la población en los procesos de vacunación. Conclusiones. La Comisión Nacional Asesora ha sido esencial en la vigilancia de la seguridad de las vacunas en Ecuador, ya que garantiza la notificación, el análisis de causalidad y la investigación de los ESAVI graves. Se identificaron desafíos que deberán ser abordados para mantener la confianza pública en los programas de vacunación.

Abstract Numerous studies focus on creating 3D-models of biological elements for geometric evaluation using CAD tools. A crucial aspect is to obtain accurate geometrical data that is easy to obtain and cost-effective for analysis. The main objective is to evaluate the geometrical accuracy of 3D-models obtained with three graphical techniques of three-dimensional geometrical documentation that characterise the fallow deer antlers in an accurate 3D-model, which is used as input data in biological analyses estimating hunting quality, asymmetry and volume. Three technologies are evaluated: structured light scanning, multi-image photogrammetry (SfM), Structure from Motion, and spatial photogrammetric restitution using two photographs in a CAD system. The geometric accuracy of the 3D-models obtained and the deviation between relevant points of the antler structure, in the main beam, in the main tines and palm, are estimated. Subsequently, the suitability of each 3D-model is studied according to the type of biological application for which it is intended. Based on the results, solid and axial 3D-models, the applicability of the three techniques for the study of biological parameters such as hunting quality, asymmetry and volume is discussed. It concludes on the most appropriate procedure to define the digital characterisation of the antler, depending on the type of biological study to be carried out in order to obtain accurate results. Characterising a geometrically complex structure such as the fallow deer antler in a 3D-model quickly and accurately can help to quantify various biomarkers in populations of specimens, making it possible to infer internal and external influencing factors.

Esta investigación aborda desde la perspectiva del enfoque en ciencia, tecnología, sociedad (CTS) la minería del diamante en Lunda Sur con el propósito de realizar un análisis de los retos y perspectiva que presenta esta actividad para lograr el desarrollo sustentable. La investigación realizada desde el paradigma cualitativo es de tipo exploratoria, se adentra un campo muy poco investigado con la intención de ofrecer una visión diferente de la relación entre la explotación de la mina de la Sociedad Minera de Catoca Lda. (SMC), el medio ambiente y las comunidades. Al ser una investigación que se adentra en un mundo se asimetrías y relaciones de profunda complejidad estratégica para el país, los resultados que se muestran aquí parte de la interpretación de la literatura, documentos y la experiencia directa en actividades en la SMC por parte de los investigadores. Las conclusiones más relevantes que se exponen parten de la relación entre los retos y las potencialidades reales que tiene esta empresa de contribuir al desarrollo sustentable de Lunda Sur a través de una minería que compense a las comunidades por los impactos negativos que ocasiona y maximice los positivos y el lugar de las tecnologías en este proceso.

Chronic wasting disease (CWD) is an emerging disease in Europe. We report an increase in interspecies transmission capacity and zoonotic potential of a moose CWD isolate from Europe after passage in an ovine prion protein–expressing host. Those results indicated some CWD prions could acquire enhanced zoonotic properties following adaptation in an intermediate species.

The concept of “codon optimisation” involves adjusting the coding sequence of a target protein to account for the inherent codon preferences of a host species and maximise protein expression in that species. However, there is still a lack of consensus on the most effective approach to achieve optimal results. Existing methods typically depend on heuristic combinations of different variables, leaving the user with the final choice of the sequence hit. In this study, we propose a new statistical-physics model for codon optimisation. This model, called the Nearest-Neighbour interaction (NN) model, links the probability of any given codon sequence to the “interactions” between neighbouring codons. We used the model to design codon sequences for different proteins of interest, and we compared our sequences with the predictions of some commercial tools. In order to assess the importance of the pair interactions, we additionally compared the NN model with a simpler method (Ind) that disregards interactions. It was observed that the NN method yielded similar Codon Adaptation Index (CAI) values to those obtained by other commercial algorithms, despite the fact that CAI was not explicitly considered in the algorithm. By utilising both the NN and Ind methods to optimise the reporter protein luciferase, and then analysing the translation performance in human cell lines and in a mouse model, we found that the NN approach yielded the highest protein expression in vivo. Consequently, we propose that the NN model may prove advantageous in biotechnological applications, such as heterologous protein expression or mRNA-based therapies.

ABSTRACT: Objective: The OXA-48-like enzymes have the capacity to hydrolyse carbapenems and are members of class D β-lactamases that are primarily detected in Enterobacterales. The allelic variant blaOXA-163, which has low hydrolytic activity towards carbapenems, was detected in Argentina in 2011 and has spread successfully since then, giving sporadic origin to novel local variants. The aim of this study was to analyse the phenotypic profile and dissemination strategies of two novel OXA enzymes, blaOXA-438 and blaOXA-567, located in Escherichia coli M17224 and Klebsiella pneumoniae M21014, respectively, isolated from two paediatric patients. Methods: Minimum inhibitory concentration measurements were performed to determine the phenotypic profile of the clinical isolates, transconjugants and transformant cells. Biparental conjugation, PCR, Sanger and whole-genome sequencing were performed to determine the complete genetic characteristics of the plasmids. Results: Both isolates were found to be resistant to carbapenems and susceptible to ceftriaxone. blaOXA-438 was located on a 69-kb IncN2 plasmid, while blaOXA-567 was found on a 175-Kb IncC2 plasmid, both transferable by biparental conjugation. The close genetic environment of the blaOXA genes suggests a common origin likely involving mobile genetic elements. Finally, the clinical case of M21014 revealed that the patient had previous infections with two genetically related K. pneumoniae ST6838 that carried blaOXA-163 on an IncC2 plasmid with equal size and genetic hallmarks to that of M21014, providing strong evidence for the intra-patient emergence of blaOXA-567. Conclusions: This research underscores the need for ongoing surveillance and integral studies to understand the emergence, biochemistry and dissemination capacity of OXA enzymes with the overarching aim to halt their spread.

Background/Objectives: Systemic sclerosis (SSc) is a chronic autoimmune disease characterized by cutaneous and visceral fibrosis, vascular alterations, and a persistent inflammatory response. Despite advances in understanding the pathogenic mechanisms underlying SSc, current therapeutic options remain limited. Chlorogenic acid (CGA) is a polyphenol widely distributed in plants and has shown antioxidant, anti-inflammatory, and antifibrotic properties. However, its therapeutic potential in SSc has not been investigated yet. Methods: A model of SSc was established by administering bleomycin (BLM) at 100 U/kg to CD1 mice via an osmotic minipump. After fourteen days of BLM administration, CGA (60 mg/kg) was intragastric administered on consecutive days until day 20. On day 21, all mice were sacrificed. The effect of CGA was histologically evaluated by hematoxylin and eosin and Masson’s trichrome staining. Results: CGA treatment significantly attenuated dermal fibrosis in the BLM-induced mice model of SSc by reducing histopathological damage, including increased dermal thickness, inflammation, collagen deposition, and SSc-associated pulmonary fibrosis. Conclusions: The evidence shows that CGA attenuates BLM-induced SSc in a mice model and strongly suggests that CGA may be a promising compound for the treatment of SSc.

Background: The current economic and social crisis in Latin America has caused migration to the USA, bringing with it Public Health challenges due to the importation of various infectious diseases. Migrants, particularly those with chronic conditions, such as HIV infection and other sexually transmitted infections (STI), are at greater risk due to pharmacological interruption and access to medical care, so the timely detection of diseases acquired during their migration, such as malaria, is crucial to avoid health complications. Objective: To outline by a multidisciplinary approach (Infectology, Parasitology, Epidemiology, molecular Biology, Venereology, and Public Health) the diagnosis and management of a male case with malaria imported to Mexican territory, HIV chronic infection, and latent syphilis. Methods: A male migrant of Venezuelan nationality attended the Clínica Especializada Condesa Iztapalapa in Mexico City for health complications. A comprehensive analysis of laboratory and molecular tests was performed to confirm HIV infection. During the STI diagnostic algorithm, latent syphilis was detected and microscopic observation of blood smears revealed parasitic forms compatible with malaria. Standard and molecular tests were applied under the operational definition for malaria cases for identification, diagnosis, and treatment. Finally, study of clinical history and migration route by questioning for the investigation of the imported case was performed. Results: The immigrant was diagnosed with HIV chronic-stage infection with interrupted antiretroviral therapy (ART), latent syphilis, and malaria by Plasmodium vivax. The ART administered was chosen based on the possible drug interaction with antimalarials and genetic barrier to the HLA-B* allele. Finally, antimicrobial therapy against syphilis was penicillin. From the analysis of the migratory route, incubation time of imported malaria, and questioning, we speculated that the migrant acquired the P. vivax infection in Panama. Conclusions: This case highlights the complex health problems faced by migrants with HIV infection, particularly when they contract additional infections such as malaria during migration and highlights the need for comprehensive access to healthcare and ART, antimalarial and antimicrobial treatments to mitigate the health risks of this vulnerable population.

Abstract Rainfed agriculture in semi-arid regions is affected by variable rainfall patterns, resulting in low yields under conventional farming systems. To address this issue, cropping systems based on conservation agriculture were evaluated in 2 field experiments on 17 farmers’ fields in the semi-arid highlands of Queretaro, Mexico, from 2013 to 2020, to assess yields and profitability. Monocropped maize (Zea mays L.) under conventional tillage was compared to growing maize on permanent beds with soil mulch, either monocropped or in rotation with triticale (X Triticum Secale Wittmack), oats (Avena sativa L.), or common beans (Phaseolus vulgaris L.). In the San Juan del Rio field experiment, maize yields on permanent beds averaged from 2,475 to 3,517 kg ha− 1 over five years, exceeding 70% the yields under conventional tillage. In the Cadereyta field experiment, 4-year average maize yields on permanent beds ranged from 979 to 1,382 kg ha− 1 with no significant difference to those under conventional tillage. In farmers’ fields, maize on permanent beds yielded an average of 3,717 kg ha− 1, 70% higher than with conventional tillage. The most profitable system was permanent beds with a maize-bean rotation in field experiments and with maize monocropping in farmers’ fields. Overall, conservation agriculture can improve maize yields and profitability in Central Mexico’s semi-arid highlands.

Abstract Primates, the most colorful mammalian radiation, have previously served as an interesting model to test the functions and evolutionary drivers of variation in eye color. We assess the contribution of photo-regulatory and communicative functions to the external eye appearance of nine macaque species representing all the branches of their radiation. Macaques’ well described social structure and wide geographical distribution make them interesting to explore. We find that (1) the posterior option of the anterior eyeball is more pigmented closer to the equator, suggesting photoprotective functions. We also find that (2) the temporal side of the eyeball is more heavily pigmented than the nasal side. This suggests that eyeball pigmentation in macaques is distributed to reduce damage to the corneal limbus. The inclusion of a translocated population of M. fuscata in our analyses also suggests that external eye appearance may change quickly, perhaps owing to phenotypic plasticity. We find no evidence that communicative functions drive variation in external eye appearance in macaques. These results suggest that the amount of light in a species’ environment drives variation in eye coloration across macaque species. Furthermore, the geographical distribution of macaques hints at important factors that have yet to be accounted for, such as the reflectivity of the terrain a given species inhabits.

Abstract With the incorporation of cyclin-dependent kinase inhibitors in early breast cancer (BC), a better identification of biomarkers is needed. The PROMETEO II trial aimed to evaluate the antitumor activity of palbociclib plus letrozole and to identify response biomarkers in patients with operable HR+/HER2- BC and residual disease after neoadjuvant chemotherapy (NAC). The primary endpoint was the rate of complete cell cycle arrest (CCCA), centrally determined by Ki67 ≤ 2.7% at surgery. A comprehensive translational analysis was conducted. At surgery, the CCCA rate was 59.1%, with a 44.2% decrease in Ki67 from the end of NAC. Changes in intrinsic subtypes occurred in 48% of patients, with proliferation genes suppressed, and immune genes more upregulated in tumors with CCCA. Overall, 14% of tumors were classified as PD-L1+ after palbociclib. Nine patients experienced grade 3 adverse events (AEs). Palbociclib showed an anti-proliferative effect, with increased immune infiltration in residual tumors with CCCA. Trial registration: Palbociclib Plus Letrozole in Hormone Receptor Positive Residual Disease After Neoadjuvant Chemotherapy (PROMETEO II) ClinicalTrial.gov number NCT04130152. Study registration; October 17, 2019.

Abstract We propose extended 3HDM and 4HDM models where the SM gauge symmetry is enlarged by the spontaneously broken $$S_4$$ S 4 group, the preserved $$Z_2$$ Z 2 and broken $$Z_4$$ Z 4 cyclic symmetries. Each model has three active SU(2) scalar doublets, in addition, the first one has an extra inert scalar singlet, whereas the second model has an inert scalar doublet. Furthermore, each model has several extra gauge singlet scalars, which are triplets under $$S_4$$ S 4 . Both models yield the same structure of the mass matrices for the fermion sector, where a radiative seesaw generates the tiny light active neutrino masses at one-loop level, through the $$S_4$$ S 4 triplets. The presence of flavor changing neutral currents mediated by heavy scalars allowed us to study the $$(K^0-\overline{K}^0)$$ ( K 0 - K ¯ 0 ) and $$(B_{d,s}^0-\overline{B}_{d,s}^0)$$ ( B d , s 0 - B ¯ d , s 0 ) meson mixings, in the parameter space that currently satisfies the experimental constraints. On the other hand, due to the preserved $$Z_2$$ Z 2 symmetry, our proposed models have stable scalar and fermionic dark matter candidates. Furthermore, these models are consistent with the current pattern of SM fermion masses and mixings, with the measured dark matter relic abundance and successfully accommodate the constraints arising from meson oscillations and oblique parameters. The extra scalars in our models provide radiative corrections to the oblique parameters, where due to the presence of the scalar inert doublet, renders the 4HDM less restrictive than the 3HDM one.

Objectives: We aim to investigate the time toxicity of patients with gastroenteropancreatic neuroendocrine tumours treated with Lutetium-177 Dotatate in a single institution. Design: This is a retrospective cohort study. Methods: All patients with gastroenteropancreatic neuroendocrine tumours treated with Lutetium-177 Dotatate at the Alexander Fleming Institute were included. Our primary endpoint was to evaluate time toxicity, which accounted for every day that the patient had contact with any department of any healthcare institution. Results: Our cohort included 21 patients with metastatic disease, female sex 86%, and a median age of 55 (IQR 44–63). The primary tumour site was the small intestine in 47.6% of the cases. The median number of previous systemic treatments for advanced disease was two (IQR 2–3). The overall response rate was 19%, and 66.6% had clinical benefit. The median calculated ‘time toxicity’ was 11 days (IQR 8–18), representing 5.7% of the total treatment duration. The main contributors to time toxicity included infusion days, blood draws, radiological scans, and hospitalisations (median of 4 days for each). Conclusion: Lutetium-177 Dotatate treatment for gastroenteropancreatic neuroendocrine tumours was associated with low time toxicity, excellent tolerability, a good response and prolonged PFS, of which the median was not reached in the short follow-up we present. Newer treatments with different mechanisms of action provide longer survival and widen the landscape of choices. Understanding new clinical endpoints is important for the transition into a more modern clinical practice, strengthening personalised and patient-oriented strategies.

Abstract Background The course of kidney function and outcomes of severe malaria infection in pregnant women is poorly understood. The indications for renal replacement therapy in pregnant patients with AKI are similar to the general population. This is the case of a pregnant patient with severe Plasmodium falciparum infection that caused cerebral malaria, acute kidney injury (AKI) who required renal replacement therapy and kidney biopsy during her hospitalization. Case presentation A 29-year-old pregnant woman from Equatorial Guinea was admitted to the hospital with haemolytic anaemia, hyperbilirubinaemia and thrombocytopenia. During hospitalization, a thick blood smear was performed where parasitaemia by P. falciparum were observed and confirmed by real-time PCR assay. The patient developed cerebral malaria secondary to an ischaemic-type cerebral vascular event, hypotension and severe. After confirming diagnosis of P. falciparum infection, artesunate, artemether/lumefantrine and primaquine were started. Kidney biopsy revealed an active tubulointerstitial nephritis with acute tubular lesion and pigment tubulopathy with negative immunofluorescence. After CVVHDF, the patient received intermittent haemodialysis until the recovery of kidney function. After discharge, follow-up was carried until the successful resolution of the pregnancy by cesarean delivery and not shown deterioration in kidney function or proteinuria. Conclusion In this case, intensive dialysis was started and dialysis intensity progressively reduced when kidney function improved. Due to the evolution of kidney function, a kidney biopsy was performed which showed tubulointerstitial nephritis as a manifestation of the infection. While the kidney biopsy was of interest for discriminating between tubular and glomerular involvement, the availability of placental biomarkers (sflt1-PlGF) would have been of help for ruling out preeclampsia and placental damage. The multidisciplinary approach to AKI during pregnancy should be the rule, with diligent care of maternal–fetal well-being during pregnancy and monitoring of kidney function after delivery.

Abstract This study aimed to evaluate the pneumonia risk based on the patient’s sex during the COVID-19 pandemic and the early months of the endemic phase of the disease in Mexico. A retrospective cohort study was conducted using a dataset resulting from the epidemiological surveillance of COVID-19 (February 2020 to August 2023). Data from 1.6 million adults with laboratory-positive disease, were analyzed. Risk ratios (RR) and 95% confidence intervals (CI), computed through generalized linear regression models, were used. The overall risk of pneumonia was 9.3% (95% CI 9.2–9.4%), with sex-specific estimates of 7.0% (95% CI 6.9–7.1%) for women and 12.0% (95% CI 11.9–12.1%) for men. This disparity was consistently observed throughout all phases of the pandemic, including the endemic phase of the disease. After adjusting for age, predominant viral genotype at illness onset and preexisting medical conditions, men had a 3.3% higher risk of severe manifestations when compared to women (RR = 1.033, 95% CI 1.032–1.034). Our research highlights the potential role of patients’ sex as a factor influencing pneumonia risk during and after the COVID-19 pandemic in Mexico. These findings may provide useful considerations for healthcare planning and policy development focused on addressing the impact of the disease on vulnerable populations.