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Introduction: The vertical transmission rate (VTR) of HIV has decreased to less than 2% in high-income countries, in spite of which perinatal infections continue to occur. We present data from the national cohort of pregnant women living with HIV and their children in Spain. The objectives were to describe the characteristics of this population, evaluate the VTR of HIV, the safety of antiretroviral therapy (ART) and the prevalence of coinfection. Patients and methods: Multicentre prospective, observational and descriptive study with participation of 62 hospitals. The sample included pegnant women living with HIV whose children were born between January 2020 and December 2022. We collected prospective data on the characteristics of mothers and children using an online questionnaire (REDCap web application). Results: The study included 414 mother-child dyads. Most mothers were immigrants (227/349; 65.1%). The main route of HIV infection was heterosexual transmission (160/402; 39.8%), followed by vertical transmission (44/402; 10.9%). The diagnosis was made before conception in 313/389 women (80.4%), 394/402 (98%) received ART during pregnancy and 356/402 (89.3%) had an undetectable viral load at the time of delivery. The delivery was vaginal in 230/388 children (59.3%). The proportion of preterm birth was 11.1%. The most frequent neonatal prophylaxis approach was monotherapy with zidovudine (358/414; 86.5%). There were 3 cases of vertical transmission of HIV (95% CI, 0%–1.54%). Only one newborn was breastfed. Conclusions: At present, most women living with HIV in Spain receive the diagnosis before conception, are of foreign ancestry and achieve good control of the infection. Although the VTR is very low in Spain, there are still infections that could be prevented with early diagnosis and treatment. Resumen: Introducción: La tasa de transmisión materno-infantil (TMI) del VIH ha disminuido a menos del 2% en países desarrollados, a pesar de lo cual siguen produciéndose infecciones. Se presentan los datos de la Cohorte Nacional Española de mujeres embarazadas que viven con VIH y sus hijos. Los objetivos fueron describir sus características, evaluar la TMI de VIH, la seguridad del tratamiento antirretroviral (TAR) y la prevalencia de coinfecciones. Pacientes y métodos: Estudio descriptivo, observacional, prospectivo y multicéntrico con participación de 62 hospitales. Se incluyeron las embarazadas cuyos hijos nacieron entre enero 2020 y diciembre 2022. Se recogieron prospectivamente características de las madres y niños en REDCap. Resultados: Hubo 414 pares madre-niño. Las madres fueron migrantes 227/349 (65,1%). La principal vía de adquisición del VIH fue la heterosexual (160/402; 39,8%), seguido de la TMI (44/402; 10,9%). En 313/389 (80,4%) el diagnóstico fue previo al embarazo, 394/402 (98%) recibieron TAR durante la gestación y 356/402 (89,3%) presentaba carga viral indetectable al parto. Hubo 230/388 (59,3%) neonatos nacidos por parto vaginal. La tasa de prematuridad fue 11,1%. La profilaxis neonatal más empleada (358/414; 86,5%) fue monoterapia con zidovudina. Hubo 3 casos de TMI del VIH (0,72% (IC 95%; 0%–1,54%), todos ellos con infección intraútero. Todos menos 1 recibieron lactancia artificial. Conclusiones: Actualmente las mujeres que viven con VIH en nuestro medio son migrantes, diagnosticadas mayoritariamente antes de la gestación, y logran adecuada situación inmunovirológica. Aunque la tasa de TMI es muy baja en nuestro país continúan ocurriendo infecciones prevenibles con diagnóstico y tratamiento más precoces.

Abstract Background Although neuroimaging investigations have consistently demonstrated that “hyperresponsive” and “hyperconnected” visual cortices may represent the functional substrate of cortical spreading depolarization in patients with migraine with aura, the mechanisms which underpin the brain “tendency” to ignite the cortical spreading depolarization and, consequently, aura phenomenon are still matter of debate. Considering that triggers able to induce aura phenomenon constrain brain to increase global (such as physical activity, stressors and sleep abnormalities) or local (such as bright light visual stimulations) energy demand, a vascular supply unable to satisfy the increased energy requirement could be hypothesized in these patients. Methods Twenty-three patients with migraine with aura, 25 patients with migraine without aura and 20 healthy controls underwent a 3-Tesla MRI study. Cerebral blood flow and local functional connectivity (regional homogeneity) maps were obtained and registered to the MNI space where 100 cortical regions were derived using a functional local-global normative parcellation. A surrogate estimate of the regional neurovascular coupling for each subject was obtained at each parcel from the correlation coefficient between the z-scored ReHo map and the z-scored cerebral blood flow maps. Results A significantly higher regional cerebral blood flow across the visual cortex of both hemispheres (i.e. fusiform and lingual gyri) was detected in migraine with aura patients when compared to patients with migraine without aura (p

Abstract Background Molar–incisor hypomineralization (MIH) is a qualitative enamel defect that is highly prevalent in children. It has been reported that patients with MIH have higher caries occurrence with an increased need and frequency of dental treatment compared to patients without MIH. The objective of this study was to analyze the association between MIH and a series of factors related to maternal health status during pregnancy and children´s medical history in early childhood. Methods A retrospective study of cases (patients with MIH) and controls (patients without MIH) was designed between 2023 and 2024. A total of 280 children (cases = 140; controls = 140) aged 6 to 14 years (138 boys and 142 girls) were examined according to the European Academy of Pediatric Dentistry (EAPD) criteria for MIH. A survey was carried out with mothers regarding the potential exposure of their children to etiological factors of MIH. Possible prenatal and postnatal etiological factors were obtained through a personal interview with the patients’ mothers. The statistical analysis was carried out with the contrast test and the chi-square test. Results During pregnancy, folic acid consumption, alcohol intake, systemic viral and/or bacterial infections, and gestational diabetes were statistically significantly related to MIH, as were breastfeeding, asthma, and corticosteroid consumption during childhood. Conclusions Although there are different factors that may have statistically significant relationships with MIH, they cannot be predicted. Therefore, longitudinal studies, with a large sample size, are needed to determine the influence of prenatal and postnatal factors on the prevalence and severity of MIH in children.

Abstract The ability to derive retinal ganglion cells (RGCs) from human pluripotent stem cells (hPSCs) has led to numerous advances in the field of retinal research, with great potential for the use of hPSC-derived RGCs for studies of human retinal development, in vitro disease modeling, drug discovery, as well as their potential use for cell replacement therapeutics. Of all these possibilities, the use of hPSC-derived RGCs as a human-relevant platform for in vitro disease modeling has received the greatest attention, due to the translational relevance as well as the immediacy with which results may be obtained compared to more complex applications like cell replacement. While several studies to date have focused upon the use of hPSC-derived RGCs with genetic variants associated with glaucoma or other optic neuropathies, many of these have largely described cellular phenotypes with only limited advancement into exploring dysfunctional cellular pathways as a consequence of the disease-associated gene variants. Thus, to further advance this field of research, in the current study we leveraged an isogenic hPSC model with a glaucoma-associated mutation in the Optineurin (OPTN) protein, which plays a prominent role in autophagy. We identified an impairment of autophagic-lysosomal degradation and decreased mTORC1 signaling via activation of the stress sensor AMPK, along with subsequent neurodegeneration in OPTN(E50K) RGCs differentiated from hPSCs, and have further validated some of these findings in a mouse model of ocular hypertension. Pharmacological inhibition of mTORC1 in hPSC-derived RGCs recapitulated disease-related neurodegenerative phenotypes in otherwise healthy RGCs, while the mTOR-independent induction of autophagy reduced protein accumulation and restored neurite outgrowth in diseased OPTN(E50K) RGCs. Taken together, these results highlighted that autophagy disruption resulted in increased autophagic demand which was associated with downregulated signaling through mTORC1, contributing to the degeneration of RGCs.

One hundred years after the publication of History and Class Consciousness, it is imperative to revisit the classic work of Georg Lukács to discuss the relevance of his ideas in a world where the capitalist mode of production does not cease to show its devastating effects. To do so, we divide the article into two sections. In the first part, we place Lukács’ work in dialogue with that of Hegel and Marx in order to clarify the status of violence as an ontological condition of history, allowing us to determine the theoretical-practical framework from which social revolution can be conceptualized. In the second section, we analyze Lukács’ notion of class consciousness not as a historical fatality but as an act of self-determination of the proletariat. We compare this proposal with the current situation of gentrification of the proletariat which, far from invalidating the Hungarian author’s proposal, constitutes its reversal and the platform for its actualization. Ultimately, it is about the proletarian still today taking control and becoming, through class consciousness, the subject-object of history. We conclude by reinterpreting Lukács’ terms in a practice that counters a reactionary position in order to combat both the reactionary movements and the hedonistic immobilism of the proletariat.

Abstract Ni-based catalysts are highly reactive for dry reforming of methane (DRM) but they are prone to rapid deactivation due to sintering and/or coking. In this study, we present a straightforward approach for anchoring dispersed Ni sites with strengthened metal-support interactions, which leads to Ni active sites embedded in dealuminated Beta zeolite with superior stability and rates for DRM. The process involves solid-state grinding of dealuminated Beta zeolites and nickel nitrate, followed by calcination under finely controlled gas flow conditions. By combining in situ X-ray absorption spectroscopy and ab initio simulations, it is elucidated that the efficient removal of byproducts during catalyst synthesis is conducted to strengthen Ni–Si interactions that suppress coking and sintering after 100 h of time-on-stream. Transient isotopic kinetic experiments shed light on the differences in intrinsic turnover frequency of Ni species and explain performance trends. This work constructs a fundamental understanding regarding the implication of facile synthesis protocols on metal-support interaction in zeolite-supported Ni sites, and it lays the needed foundations on how these interactions can be tuned for outstanding DRM performance.

Objetivos. Determinar la alimentación del Aedes aegypti en brotes de dengue de dos zonas rurales del Perú durante el ciclón Yaku y El Niño Global del 2023. Material métodos. Se analizaron ocho muestras de sangre (8 pooles) obtenidas del abdomen de 80 especímenes Aedes aegypti capturados en los distritos rurales de Querecotillo y Marcavelica durante brotes de dengue acontecidos en el ciclón Yaku y en El Niño Global. Se extrajo ADN de las muestras analizadas, se llevó a cabo una PCR dirigida al gen CytB como marcador genético y los productos PCR fueron digeridos enzimáticamente con las restrictasas Hae III y Mwo I. Los productos PCR-RFLP fueron visualizados por electroforesis en gel de agarosa al 4%. Resultados. Se obtuvo ADN de todas las muestras y como producto PCR un amplicón de 358 pb. Así mismo, el único RFLP en Hae III observado fue el de Homo sapiens sapiens (233 y 125 pb). No se observó RFLP en Hae III de Gallus gallus y RFLP en Mwo I de Canis familiaris y Mus musculus. Conclusión. En brotes de dengue de zonas rurales, durante el ciclón Yaku y en El Niño Global, el Aedes aegypti presentó un comportamiento alimenticio antropofílico conservado.

Con el objetivo del estudio fue determinar la coexistencia y fuentes de alimentación de mosquitos adultos (Diptera: Culicidae) en un centro de salud rural de Piura en Perú, se realizó un estudio descriptivo transversal. Se usaron técnicas entomológicas para capturar e identificar mosquitos, y técnicas de biotecnología molecular para identificar las fuentes de alimentación. Un total de 793 ejemplares de los géneros Culex y Aedes se encontraron coexistiendo, 789 (99,5%) corresponden a Culex quinquefasciatus, 607 (76,9%) fueron machos y 182 (23,1%) hembras. Así mismo, 4 (100%) corresponden a Aedes aegypti hembras. Las fuentes de alimentación de Aedes aegypti fueron Homo sapiens sapiens, y de Culex quinquefasciatus fueron Homo sapiens sapiens y Canis familiaris. Este estudio proporciona evidencia de que los centros de salud rurales estarían actuando como focos de arbovirosis, existiendo el riesgo de que personas que acuden por distintas dolencias, puedan contraer enfermedades transmitidas por C. quinquefasciatus y A. aegypti.

Abstract Background Hidradenitis suppurativa (HS) is a chronic inflammatory disease that leads to the formation of nodules, abscesses and fistulas, with the formation of scars and fibrosis, causing significant impairment in patient quality of life. The diagnosis is clinical, using scores to classify the severity of the condition; currently the most recommended classification is the International Hidradenitis Suppurativa Severity Scoring System (IHS4). Doppler ultrasound has been used to complement the clinical evaluation of patients with HS. It is possible to observe subclinical lesions that change the staging, the severity of the case, and its treatment, either clinical or surgical. Correct treatment is essential to minimize the consequences of this disease for the patient. Objective To establish an outpatient protocol for the use of Doppler ultrasound in the care of patients with HS. Methods A narrative review of the literature was carried out on the use of Doppler ultrasound in patients with hidradenitis suppurativa; a referring protocol and technique orientations for imaging assessment in HS were created. Results Recommendation to perform ultrasound evaluation of symptomatic areas eight weeks after using antibiotics and four, 12, and 24 weeks after starting immunobiologicals; apply SOS-HS ultrasound severity classification. Study limitations The review did not cover all literature on ultrasound and HS; no systematic review was carried out, but rather a narrative one. Conclusions The correct assessment of patients staging must be carried out using dermatological ultrasound to avoid progression to scars and fibrosis, which compromise patients quality of life.

Therapeutic monitoring of antibiotics and antifungals based on pharmacokinetic and pharmacodynamic (PK/PD) parameters is a strategy increasingly used for the optimization of therapy to improve efficacy, reduce the occurrence of toxicities, and prevent the selection of antimicrobial resistance, particularly in vulnerable patients including neonates and the critical or immunocompromised paediatric host.In neonates and children, infections account for a high percentage of hospital admissions, and anti-infectives are the most used drugs. However, paediatric PK/PD studies and the evidence regarding the efficacy and safety of some newly marketed antibiotics and antifungals—usually used off-label in paediatrics—to determine the optimal drug dosage regimens are limited. It is widely known that this population presents important differences in the PK parameters (especially in drug clearance and volume of distribution) in comparison with adults that may alter antimicrobial exposure and, therefore, compromise treatment success. In addition, paediatric patients are more susceptible to potential adverse drug effects and they need closer monitoring.The aim of this document, developed jointly by the Spanish Society of Hospital Pharmacy and the Spanish Society of Paediatric Infectious Diseases, is to describe the available evidence on the indications for therapeutic drug monitoring (TDM) of antibiotics and antifungals in newborn and paediatric patients, and to provide practical recommendations for TDM in routine clinical practice to optimise their dosing, efficacy and safety. Of antibiotics and antifungals in the paediatric population. Resumen: La monitorización terapéutica de antibióticos y antifúngicos en el paciente pediátrico, basada en parámetros farmacocinéticos y farmacodinámicos (PK/PD), es una estrategia cada vez más utilizada para la optimización del tratamiento de infecciones con el fin de mejorar la eficacia, reducir la aparición de toxicidades y prevenir la selección de resistencias antimicrobianas, especialmente en poblaciones vulnerables como neonatos, pacientes críticos o inmunodeprimidos.En la población neonatal y pediátrica, las infecciones representan un porcentaje elevado de los ingresos hospitalarios, siendo los antimicrobianos los fármacos más utilizados en este grupo poblacional. Sin embargo, establecer los regímenes posológicos óptimos en esta población es complejo debido a la menor evidencia respecto a la eficacia y seguridad de algunos antimicrobianos, especialmente en los de reciente comercialización que son utilizados habitualmente fuera de ficha técnica y al limitado número de estudios PK/PD disponibles en pediatría. Es bien conocido que el paciente pediátrico se caracteriza por presentar una serie de variaciones de los parámetros farmacocinéticos (como el aclaramiento o el volumen de distribución) debido a los propios cambios madurativos que pueden modificar la exposición a los antimicrobianos y comprometer el éxito del tratamiento. A su vez, es un grupo poblacional más susceptible a presentar potenciales efectos adversos a los fármacos, hecho que conlleva la necesidad de una monitorización más estricta.El objetivo de este documento de consenso, elaborado entre la Sociedad Española de Farmacia Hospitalaria (SEFH) y Sociedad Española de Infectología Pediátrica (SEIP), es describir la evidencia disponible sobre las indicaciones de la monitorización terapéutica de antibióticos y antifúngicos en pacientes neonatales y pediátricos, y proporcionar recomendaciones prácticas para su monitorización y ajuste de dosis, con el fin de optimizar el tratamiento, maximizando su eficacia y seguridad.

Abstract The coordinated action of transcriptional and post-transcriptional machineries shapes gene expression programs at steady state and determines their concerted response to perturbations. We have developed Nanodynamo, an experimental and computational workflow for quantifying the kinetic rates of nuclear and cytoplasmic steps of the RNA life cycle. Nanodynamo is based on mathematical modelling following sequencing of native RNA from cellular fractions and polysomes. We have applied this workflow to triple-negative breast cancer cells, revealing widespread post-transcriptional RNA processing that is mutually exclusive with its co-transcriptional counterpart. We used Nanodynamo to unravel the coupling between transcription, processing, export, decay and translation machineries. We have identified a number of coupling interactions within and between the nucleus and cytoplasm that largely contribute to coordinating how cells respond to perturbations that affect gene expression programs. Nanodynamo will be instrumental in unravelling the determinants and regulatory processes involved in the coordination of gene expression responses.

Objetivo: Estimar la relación entre la percepción del clima ergonómico de la empresa y la presencia de molestias musculoesqueléticas en trabajadores de tres ciudades colombianas. Metodología: Estudio de corte en 1339 trabajadores de empresas de diversos sectores económicos, ubicadas en Barranquilla, Bogotá y Cúcuta. El estudio se realizó desde septiembre hasta diciembre de 2021. Se aplicaron el Cuestionario Evaluación del Clima Ergonómico y el Cuestionario Nórdico Musculoesquelético para la evaluación de molestias musculoesqueléticas. Resultados: La mayoría de las molestias fueron en el cuello (48,88 %). El 48,69 % de los trabajadores encuestados considera que su formación y conocimiento sobre bienestar y salud en el ámbito laboral es baja. La percepción de molestias musculoesqueléticas en el cuello fue mayor en los trabajadores con baja percepción del compromiso de la Gerencia con los indicadores empresariales [OR 1,77 (IC 95 %: 1,24-2,51)] y con el bienestar y la salud [OR 2,56 (IC 95 %: 1,75-3,75)]. La baja formación y conocimiento de los empleados sobre los indicadores empresariales se relacionó con mayores molestias en hombros [OR 1,8 (IC 95 %: 1,26-2,58)] y codos [OR 2,3 (IC 95 %: 1,38-3,62)], y sobre el bienestar y la salud, con molestias en zona alta de la espalda [OR 3,7 (IC 95 %: 2,60-5,25)], cadera, nalgas, muslos [OR 3,19 (IC 95 %: 2,19-4,66)] y rodillas [OR 4,42 (IC 95 %: 3,02-6,46)]. Conclusión: La presencia de molestias musculoesqueléticas está relacionada con la falta de compromiso de la empresa con la gestión de un ambiente saludable, la participación de los trabajadores en las actividades de seguridad y salud en el trabajo, el análisis de riesgos laborales y los procesos de formación de los trabajadores

Abstract Nothofagus antarctica (G.Forst.) Oerst. (Ñire) leaves are a valuable source of (poly)phenolic compounds and represent a high-value non-timber product from Patagonian forests. However, information on the variability of their chemical profile is limited or non-existent. The aim of this study was to evaluate the (poly)phenolic variability in Ñire leaf infusions. To this end, different tree populations growing under different temperature regimes and soil characteristics were considered. Interestingly, a cup of Ñire leaf infusion could be considered as a rich source of quercetin. Significant differences in the (poly)phenolic content, especially in flavonoid conjugates and cinnamic acids, were found among the populations studied. These results suggest metabolic variability among the forests studied, which could be related to the species response to its growing conditions, and also provide some clues about the performance of N. antarctica under future climate scenarios. The N. antarctica forests growing in environments with lower frequency of cold and heat stress and high soil fertility showed better infusion quality. This study showed how a South American beech interacts with its local environment at the level of secondary metabolism. In addition, the information obtained is useful for defining forest management strategies in the Patagonian region.

Abstract The escape of mitochondrial double-stranded dsRNA (mt-dsRNA) into the cytosol has been recently linked to a number of inflammatory diseases. Here, we report that the release of mt-dsRNA into the cytosol is a general feature of senescent cells and a critical driver of their inflammatory secretome, known as senescence-associated secretory phenotype (SASP). Inhibition of the mitochondrial RNA polymerase, the dsRNA sensors RIGI and MDA5, or the master inflammatory signaling protein MAVS, all result in reduced expression of the SASP, while broadly preserving other hallmarks of senescence. Moreover, senescent cells are hypersensitized to mt-dsRNA-driven inflammation due to their reduced levels of PNPT1 and ADAR1, two proteins critical for mitigating the accumulation of mt-dsRNA and the inflammatory potency of dsRNA, respectively. We find that mitofusin MFN1, but not MFN2, is important for the activation of the mt-dsRNA/MAVS/SASP axis and, accordingly, genetic or pharmacologic MFN1 inhibition attenuates the SASP. Finally, we report that senescent cells within fibrotic and aged tissues present dsRNA foci, and inhibition of mitochondrial RNA polymerase reduces systemic inflammation associated to senescence. In conclusion, we uncover the mt-dsRNA/MAVS/MFN1 axis as a key driver of the SASP and we identify novel therapeutic strategies for senescence-associated diseases.

Abstract In this study, we evaluated and forecasted the cumulative opportunities for residents to access radiotherapy services in Cali, Colombia, while accounting for traffic congestion, using a new people-centred methodology with an equity focus. Furthermore, we identified 1–2 optimal locations where new services would maximise accessibility. We utilised open data and publicly available big data. Cali is one of South America's cities most impacted by traffic congestion. Methodology: Using a people-centred approach, we tested a web-based digital platform developed through an iterative participatory design. The platform integrates open data, including the location of radiotherapy services, the disaggregated sociodemographic microdata for the population and places of residence, and big data for travel times from Google Distance Matrix API. We used genetic algorithms to identify optimal locations for new services. We predicted accessibility cumulative opportunities (ACO) for traffic ranging from peak congestion to free-flow conditions with hourly assessments for 6–12 July 2020 and 23–29 November 2020. The interactive digital platform is openly available. Primary and secondary outcomes: We present descriptive statistics and population distribution heatmaps based on 20-min accessibility cumulative opportunities (ACO) isochrones for car journeys. There is no set national or international standard for these travel time thresholds. Most key informants found the 20-min threshold reasonable. These isochrones connect the population-weighted centroid of the traffic analysis zone at the place of residence to the corresponding zone of the radiotherapy service with the shortest travel time under varying traffic conditions ranging from free-flow to peak-traffic congestion levels. Additionally, we conducted a time-series bivariate analysis to assess geographical accessibility based on economic stratum. We identify 1–2 optimal locations where new services would maximize the 20-min ACO during peak-traffic congestion. Results: Traffic congestion significantly diminished accessibility to radiotherapy services, particularly affecting vulnerable populations. For instance, urban 20-min ACO by car dropped from 91% of Cali’s urban population within a 20-min journey to the service during free-flow traffic to 31% during peak traffic for the week of 6–12 July 2020. Percentages represent the population within a 20-min journey by car from their residence to a radiotherapy service. Specific ethnic groups, individuals with lower educational attainment, and residents on the outskirts of Cali experienced disproportionate effects, with accessibility decreasing to 11% during peak traffic compared to 81% during free-flow traffic for low-income households. We predict that strategically adding sufficient services in 1–2 locations in eastern Cali would notably enhance accessibility and reduce inequities. The recommended locations for new services remained consistent in both of our measurements. These findings underscore the significance of prioritising equity and comprehensive care in healthcare accessibility. They also offer a practical approach to optimising service locations to mitigate disparities. Expanding this approach to encompass other transportation modes, services, and cities, or updating measurements, is feasible and affordable. The new approach and data are particularly relevant for planning authorities and urban development actors.

Abstract Converging evidence indicates that extra-embryonic yolk sac is the source of both macrophages and endothelial cells in adult mouse tissues. Prevailing views are that these embryonically derived cells are maintained after birth by proliferative self-renewal in their differentiated states. Here we identify clonogenic endothelial-macrophage (EndoMac) progenitor cells in the adventitia of embryonic and postnatal mouse aorta, that are independent of Flt3-mediated bone marrow hematopoiesis and derive from an early embryonic CX3CR1+ and CSF1R+ source. These bipotent progenitors are proliferative and vasculogenic, contributing to adventitial neovascularization and formation of perfused blood vessels after transfer into ischemic tissue. We establish a regulatory role for angiotensin II, which enhances their clonogenic and differentiation properties and rapidly stimulates their proliferative expansion in vivo. Our findings demonstrate that embryonically derived EndoMac progenitors participate in local vasculogenic responses in the aortic wall by contributing to the expansion of endothelial cells and macrophages postnatally.

Abstract The prognosis of patients with advanced high-grade (G3) digestive neuroendocrine neoplasms (NENs) is rather poor. The addition of immune checkpoint inhibition to platinum-based chemotherapy may improve survival. NICE-NEC (NCT03980925) is a single-arm, phase II trial that recruited chemotherapy-naive, unresectable advanced or metastatic G3 NENs of gastroenteropancreatic (GEP) or unknown origin. Patients received nivolumab 360 mg intravenously (iv) on day 1, carboplatin AUC 5 iv on day 1, and etoposide 100 mg/m2/d iv on days 1–3, every 3 weeks for up to six cycles, followed by nivolumab 480 mg every 4 weeks for up to 24 months, disease progression, death or unacceptable toxicity. The primary endpoint was the 12-month overall survival (OS) rate (H0 50%, H1 72%, β 80%, α 5%). Secondary endpoints were objective response rate (ORR), duration of response (DoR), progression-free survival (PFS), and safety. From 2019 to 2021, 37 patients were enrolled. The most common primary sites were the pancreas (37.8%), stomach (16.2%) and colon (10.8%). Twenty-five patients (67.6%) were poorly differentiated carcinomas (NECs) and/or had a Ki67 index >55%. The ORR was 56.8%. Median PFS was 5.7 months (95%CI: 5.1-9) and median OS 13.9 months (95%CI: 8.3-Not reached), with a 12-month OS rate of 54.1% (95%CI: 40.2-72.8) that did not meet the primary endpoint. However, 37.6% of patients were long-term survivors (>2 years). The safety profile was consistent with previous reports. There was one treatment-related death. Nivolumab plus platinum-based chemotherapy was associated with prolonged survival in over one-third of chemonaïve patients with G3 GEP-NENs, with a manageable safety profile.

Previous studies reported that a substantial number of students with autism spectrum disorder (ASD) encounter challenges in mathematics as they advance through their education. The present study evaluates the mathematical competence of 17 students diagnosed with ASD who were recruited from first through fourth grades in 12 different mainstream schools. The results were compared with those from other 17 students without ASD, matched one-to-one by sex and school (grade and classroom). In general, the students with ASD in this study exhibited greater difficulties in mathematics than their peers without ASD. These difficulties were particularly noticeable in fourth graders, although they could be observed earlier in informal skills. Many students with ASD in the sample struggled with informal calculation and concepts, as well as with all formal categories considered, particularly calculation and concepts. These findings may be relevant for early teaching interventions and for the development of future mathematical learning supports for students with ASD.

This study examines relationships between mathematical problem-solving performance (in terms of strategies used and accuracy) and the main cognitive domains associated with mathematical learning (i.e. executive functions, verbal comprehension and social perception) of children with and without autism spectrum disorder (ASD and non-ASD resp.). The study involved 26 ASD and 26 non-ASD children without intellectual disabilities, between 6 and 12 years old, matched by sex, age and school (grade and classroom). The results show a higher percentage of ASD children with problem solving difficulties than non-ASD (57% vs. 23% resp.). Poor performing ASD children showed comparatively lower scores in inhibition, theory of mind and verbal comprehension. Implications for the design of mathematical interventions for ASD students are discussed.

This study, which used a multiple baseline across participants' design, examines the effectiveness of a modified schema-based instructional approach to improve the mathematical word problem solving performance of three students with mild intellectual disability, two of whom had an autism spectrum disorder. Following the intervention, the three students improved their performance when solving addition and subtraction change word problems; however, their performance was inconsistent on change word problems. The effects of the instruction were generalized to two-step addition and subtraction word problems for the three participants. Moreover, the results were generalized to an untrained setting and were maintained 8 weeks after the instruction. The implications of these findings for teaching problem-solving skills to students with intellectual disability are discussed.

This study focuses on the challenge of introducing cooperative entrepreneurship as an option for university business students, as recommended by the Social Economy Action Plan (SEAP) adopted in the European Union (EU). This aim is linked to Sustainable Development Goal (SDG) 4, which calls for efforts to ensure quality education for all. Our study jointly addresses both entrepreneurship and the need for high-quality education among the university students we are analysing. The use of success stories in cooperative entrepreneurship is based on a Best Practice Learning (BPL) methodology. The students under analysis are categorized into two areas of knowledge, law and economics, depending on whether the main content of their studies focuses on aspects of law or on purely economic aspects. The results show an increased interest in cooperative entrepreneurship in all participants after the application of BPL, and a high level of satisfaction with the activities carried out as part of this experience. However, differences were found between economics and law students, with the former having more knowledge about the concept of entrepreneurship. On the other hand, the latter group shows a greater awareness of the importance of cooperativism. The results of this study can provide the basis for new initiatives at the university level, aimed at the promotion of cooperative entrepreneurship in line with its key role in the SEAP and the SDGs.

Retinal ganglion cell (RGC) death in glaucoma and other optic neuropathies results in irreversible vision loss due to the mammalian central nervous systems limited regenerative capacity. RGC repopulation is a promising therapeutic approach to reverse vision loss from optic neuropathies if the newly introduced neurons can reestablish functional retinal and thalamic circuits. In theory, RGCs might be repopulated through the transplantation of stem cell-derived neurons or via the induction of endogenous transdifferentiation. The RGC Repopulation, Stem Cell Transplantation, and Optic Nerve Regeneration (RReSTORe) Consortium was established to address the challenges associated with the therapeutic repair of the visual pathway in optic neuropathy. In 2022, the RReSTORe Consortium initiated ongoing international collaborative discussions to advance the RGC repopulation field and has identified five critical areas of focus: (1) RGC development and differentiation, (2) Transplantation methods and models, (3) RGC survival, maturation, and host interactions, (4) Inner retinal wiring, and (5) Eye-to-brain connectivity. Here, we discuss the most pertinent questions and challenges that exist on the path to clinical translation and suggest experimental directions to propel this work going forward. Using these five subtopic discussion groups (SDGs) as a framework, we suggest multidisciplinary approaches to restore the diseased visual pathway by leveraging groundbreaking insights from developmental neuroscience, stem cell biology, molecular biology, optical imaging, animal models of optic neuropathy, immunology & immunotolerance, neuropathology & neuroprotection, materials science & biomedical engineering, and regenerative neuroscience. While significant hurdles remain, the RReSTORe Consortiums efforts provide a comprehensive roadmap for advancing the RGC repopulation field and hold potential for transformative progress in restoring vision in patients suffering from optic neuropathies.

Abstract: The tropical forest carbon sink is known to be drought sensitive, but it is unclear which forests are the most vulnerable to extreme events. Forests with hotter and drier baseline conditions may be protected by prior adaptation, or more vulnerable because they operate closer to physiological limits. Here we report that forests in drier South American climates experienced the greatest impacts of the 2015–2016 El Niño, indicating greater vulnerability to extreme temperatures and drought. The long-term, ground-measured tree-by-tree responses of 123 forest plots across tropical South America show that the biomass carbon sink ceased during the event with carbon balance becoming indistinguishable from zero (−0.02 ± 0.37 Mg C ha−1 per year). However, intact tropical South American forests overall were no more sensitive to the extreme 2015–2016 El Niño than to previous less intense events, remaining a key defence against climate change as long as they are protected.

Transcatheter aortic valve replacement (TAVR) has shown good early and midterm results from high risk to low surgical risk patients with severe symptomatic aortic valve stenosis. Despite low adverse events, TAVR is associated with vascular injury, bleeding, stroke, and conduction system disturbances as the most common adverse events. Aortic dissection is a relatively rare but potentially lethal complication from TAVR. Here, we report a case of ascending aortic dissection (type A) complicating TAVR that was managed conservatively with complete resolution of the complication noted on serial computed tomography angiogram.