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Background: Despite the number of research studies regarding the individual burden of migraine, few studies have examined its impact on the patients’ partners. We aim to assess migraine effects on the patients’ partners on sentimental relationship, children relationship, friendship, and work, as well as the caregiver burden, anxiety and/or depression. Methods: A cross-sectional observational study was conducted through an online survey of partners of patients with migraine followed-up in 5 Headache Units. Questions about the 4 areas of interest and 2 scales (Hospital Anxiety and Depression Scale and Zarit scale) were included. Scores were compared against the population prevalence. Results: One hundred and fifty-five answers were analysed. Among the patient’s partners 135/155 (87.1%) were men, with a mean age of 45.6 ± 10.1 years. Migraine’s main effects on partners were observed in the sentimental relationship and items concerning children and friendships, with a minor impact at work. Partners showed a moderate burden (12/155 = 7.7% [4.1%–13.1%]), and a higher moderate-severe anxiety rate (23/155 = 14.8% [9.6%–21.4%]), and similar depression rate (5/155 = 3.2% [1.1%–7.3%]) compared to the National Health Survey. Conclusions: The burden of migraine impacts the partners’ personal relationship, childcare, friendship and work. Moreover, certain migraine partners showed a moderate burden according to Zarit scale and higher anxiety levels than the Spanish population. Resumen: Introducción y objetivos: Diversos estudios han evaluado la sobrecarga individual de la migraña, sin embargo, pocos estudios han examinado su impacto en las parejas de los pacientes. Nuestro objetivo es evaluar los efectos de la migraña en las parejas de los pacientes sobre la relación sentimental, la relación con los hijos, la amistad y el trabajo, así como la sobrecarga del cuidador, la ansiedad y/o la depresión. Material y métodos: Se realizó un estudio observacional transversal a través de un cuestionario en línea a las parejas de pacientes con migraña seguidos en cinco Unidades de Cefalea. Se incluyeron preguntas sobre las cuatro áreas de interés y dos escalas (Escala de Ansiedad y Depresión Hospitalaria y escala de Zarit). Las puntuaciones se compararon con la prevalencia de la población según la Encuesta Nacional de Salud. Resultados: Se analizaron ciento cincuenta y cinco respuestas. Las parejas de los pacientes con migraña fueron 135/155 (87.1%) hombres, edad media de 45.6 ± 10.1 years; Los principales efectos de la migraña en la pareja se observaron en la relación sentimental y en los ítems relativos a los hijos y las amistades, con menor impacto en el trabajo. Las parejas mostraron una carga moderada (12/155 = 7,7%[4,1%-13,1%]), y una tasa de ansiedad moderada-grave más alta (23/155 = 14,8%[9,6%-21,4%]) y una tasa de depresión similar (5/155 = 3,2%[1,1%-7,3%]) respecto a la población española. Conclusiones: La carga de la migraña tiene un impacto en la relación personal de la pareja, el cuidado de los hijos, la amistad y el trabajo. Además, algunos cuidadores de pacientes con migraña presentan una carga moderada y niveles de ansiedad más altos que la población española.

Abstract Drug resistance remains a challenge for targeted therapy of cancers driven by EML4-ALK and related fusion oncogenes. EML4-ALK forms cytoplasmic protein condensates, which result from networks of interactions between oncogene and adapter protein multimers. While these assemblies are associated with oncogenic signaling, their role in drug response is unclear. Here, we use optogenetics and live-cell imaging to find that EML4-ALK assemblies suppress transmembrane receptor tyrosine kinase (RTK) signaling by sequestering RTK adapter proteins including GRB2 and SOS1. Furthermore, ALK inhibition, while suppressing oncogenic signaling, simultaneously releases the sequestered adapters and thereby resensitizes RTK signaling. Resensitized RTKs promote rapid and pulsatile ERK reactivation that originates from paracrine ligands shed by dying cells. Reactivated ERK signaling promotes cell survival, which can be counteracted by combination therapies that block paracrine signaling. Our results identify a regulatory role for RTK fusion assemblies and uncover a mechanism of tolerance to targeted therapies.

Abstract Over the past years, there has been a sustained effort to systematically enhance our understanding of medium-induced emissions occurring in the quark-gluon plasma, driven by the ultimate goal of advancing our comprehension of jet quenching phenomena. To ensure meaningful comparisons between these new calculations and experimental data, it becomes crucial to model the interplay between the radiation process and the evolution of the medium parameters, typically described by a hydrodynamical simulation. This step presents particular challenges when dealing with calculations involving the resummation of multiple scatterings, which have been shown to be necessary for achieving an accurate description of the in-medium emission process. In this paper, we extend our numerical calculations of the fully-resummed gluon spectrum to account for longitudinally expanding media. This new implementation allows us to quantitatively assess the accuracy of previously proposed scaling laws that establish a correspondence between an expanding medium and a “static equivalent”. Additionally, we show that such scaling laws yield significantly improved results when the static reference case is replaced by an expanding medium with the temperature following a simple power-law decay. Such correspondence will enable the application of numerical calculations of medium-induced energy loss in realistic evolving media for a broader range of phenomenological studies.

Background: Despite the number of research studies regarding the individual burden of migraine, few studies have examined its impact on the patients’ partners. We aim to assess migraine effects on the patients’ partners on sentimental relationship, children relationship, friendship, and work, as well as the caregiver burden, anxiety and/or depression. Methods: A cross-sectional observational study was conducted through an online survey of partners of patients with migraine followed-up in 5 Headache Units. Questions about the 4 areas of interest and 2 scales (Hospital Anxiety and Depression Scale and Zarit scale) were included. Scores were compared against the population prevalence. Results: One hundred and fifty-five answers were analysed. Among the patient’s partners 135/155 (87.1%) were men, with a mean age of 45.6 ± 10.1 years. Migraine’s main effects on partners were observed in the sentimental relationship and items concerning children and friendships, with a minor impact at work. Partners showed a moderate burden (12/155 = 7.7% [4.1%–13.1%]), and a higher moderate-severe anxiety rate (23/155 = 14.8% [9.6%–21.4%]), and similar depression rate (5/155 = 3.2% [1.1%–7.3%]) compared to the National Health Survey. Conclusions: The burden of migraine impacts the partners’ personal relationship, childcare, friendship and work. Moreover, certain migraine partners showed a moderate burden according to Zarit scale and higher anxiety levels than the Spanish population. Resumen: Introducción y objetivos: Diversos estudios han evaluado la sobrecarga individual de la migraña, sin embargo, pocos estudios han examinado su impacto en las parejas de los pacientes. Nuestro objetivo es evaluar los efectos de la migraña en las parejas de los pacientes sobre la relación sentimental, la relación con los hijos, la amistad y el trabajo, así como la sobrecarga del cuidador, la ansiedad y/o la depresión. Material y métodos: Se realizó un estudio observacional transversal a través de un cuestionario en línea a las parejas de pacientes con migraña seguidos en cinco Unidades de Cefalea. Se incluyeron preguntas sobre las cuatro áreas de interés y dos escalas (Escala de Ansiedad y Depresión Hospitalaria y escala de Zarit). Las puntuaciones se compararon con la prevalencia de la población según la Encuesta Nacional de Salud. Resultados: Se analizaron ciento cincuenta y cinco respuestas. Las parejas de los pacientes con migraña fueron 135/155 (87.1%) hombres, edad media de 45.6 ± 10.1 years; Los principales efectos de la migraña en la pareja se observaron en la relación sentimental y en los ítems relativos a los hijos y las amistades, con menor impacto en el trabajo. Las parejas mostraron una carga moderada (12/155 = 7,7%[4,1%-13,1%]), y una tasa de ansiedad moderada-grave más alta (23/155 = 14,8%[9,6%-21,4%]) y una tasa de depresión similar (5/155 = 3,2%[1,1%-7,3%]) respecto a la población española. Conclusiones: La carga de la migraña tiene un impacto en la relación personal de la pareja, el cuidado de los hijos, la amistad y el trabajo. Además, algunos cuidadores de pacientes con migraña presentan una carga moderada y niveles de ansiedad más altos que la población española.

Abstract Cerebral white matter lesions prevent cortico-spinal descending inputs from effectively activating spinal motoneurons, leading to loss of motor control. However, in most cases, the damage to cortico-spinal axons is incomplete offering a potential target for therapies aimed at improving volitional muscle activation. Here we hypothesize that, by engaging direct excitatory connections to cortico-spinal motoneurons, stimulation of the motor thalamus could facilitate activation of surviving cortico-spinal fibers thereby immediately potentiating motor output. To test this hypothesis, we identify optimal thalamic targets and stimulation parameters that enhance upper-limb motor-evoked potentials and grip forces in anesthetized monkeys. This potentiation persists after white matter lesions. We replicate these results in humans during intra-operative testing. We then design a stimulation protocol that immediately improves strength and force control in a patient with a chronic white matter lesion. Our results show that electrical stimulation targeting surviving neural pathways can improve motor control after white matter lesions.

El objetivo de la investigación fue explorar sobre las vulnerabilidades de ataques SSRF, visto desde las temáticas trabajadas en investigaciones recientes y los reportes internacionales. La metodología consistió en la revisión sistemática que permite conocer el estado actual abordada a partir de las siguientes interrogantes: ¿Cuál es la tendencia en detecciones de ataques SSFR? ¿Cuáles son las principales técnicas para identificar este tipo de vulnerabilidad? ¿Cómo se manifiestan los ataques SSFR? ¿Qué herramientas se emplean para identificar este tipo de vulnerabilidad? ¿Cuáles son las medidas para mitigar que se explote este tipo de vulnerabilidad? Las bases de datos utilizadas fueron IEEE, ACM, Elservier tomando como período desde el año 2020 al 2024. Los resultados muestran que anualmente se reporta un incremento en los ataques SSRF, con un aumento significativo año por año, las principales técnicas para identificar las vulnerabilidades de SSRF son: el análisis estático y dinámico de código, las pruebas de penetración y la revisión de configuraciones y políticas de seguridad. Estas vulnerabilidades se manifiestan comúnmente a través de la exfiltración de datos y la evasión de controles de seguridad. Para la detección de vulnerabilidades SSRF se utilizan herramientas como: Burp Suite, OWASP Zap y Nikto. Las medidas para mitigar la explotación de vulnerabilidades SSRF incluyen la validación y análisis de entradas, la segregación de redes y servicios, el uso de listas blancas y negras, y el monitoreo continuo. Se concluye que las vulnerabilidades de ataques SSRF son una amenaza para la transformación digital.

Abstract Background Chronic lung disease (CLD) is common among children with HIV (CWH) including in those taking antiretroviral therapy (ART). Azithromycin has both antimicrobial and anti-inflammatory effects and has been effective in improving lung function in a variety of lung diseases. We investigated lung function trajectories among CWH with CLD on ART enrolled in a randomized controlled trial of adjuvant azithromycin. We also investigated factors that modified the effect of azithromycin on lung function. Methods The study used data from a double-blinded placebo-controlled trial conducted in Malawi and Zimbabwe of 48 weeks on azithromycin (BREATHE: ClinicalTrials.gov NCT02426112) among CWH aged 6 to 19 years taking ART for at least six months who had a forced expiratory volume in one second (FEV1) z-score

Abstract Recently, targeted degradation has emerged as a powerful therapeutic modality. Relying on “event-driven” pharmacology, proteolysis targeting chimeras (PROTACs) can degrade targets and are superior to conventional inhibitors against undruggable proteins. Unfortunately, PROTAC discovery is limited by warhead scarcity and laborious optimization campaigns. To address these shortcomings, analogous protein-based heterobifunctional degraders, known as bioPROTACs, have been developed. Compared to small-molecule PROTACs, bioPROTACs have higher success rates and are subject to fewer design constraints. However, the membrane impermeability of proteins severely restricts bioPROTAC deployment as a generalized therapeutic modality. Here, we present an engineered bioPROTAC template able to complex with cationic and ionizable lipids via electrostatic interactions for cytosolic delivery. When delivered by biocompatible lipid nanoparticles, these modified bioPROTACs can rapidly degrade intracellular proteins, exhibiting near-complete elimination (up to 95% clearance) of targets within hours of treatment. Our bioPROTAC format can degrade proteins localized to various subcellular compartments including the mitochondria, nucleus, cytosol, and membrane. Moreover, substrate specificity can be easily reprogrammed, allowing modular design and targeting of clinically-relevant proteins such as Ras, Jnk, and Erk. In summary, this work introduces an inexpensive, flexible, and scalable platform for efficient intracellular degradation of proteins that may elude chemical inhibition.

Abstract BackgroundPatients with cancer often face depression and anxiety, and mindfulness-based interventions, including internet-based versions, can effectively reduce these symptoms and improve their quality of life. This study aims to investigate the impact of internet-based mindfulness-based interventions (e-MBIs) on anxiety, depression, and stress symptoms in patients with prostate or breast cancer. ObjectiveThe primary aims are to assess the association between the amount and variety of e-MBI practices and symptom reduction. Second, this study aims to examine how baseline information such as sociodemographic characteristics, dispositional mindfulness (DM), and dispositional self-compassion (DSC) correlate with both app usage and symptom reduction. MethodsParticipants included 107 patients with cancer (68 women with breast cancer and 38 men with prostate cancer) enrolled in a hospital setting. They were assigned to the intervention group of the NEVERMIND project, using the e-BMI module via the NEVERMIND app. A longitudinal design involved Pearson correlation analysis to determine the relationship between the amount and duration of e-MBI practices. Linear regression analysis was conducted to gauge the dose-response effect, evaluating the impact of DM and DSC on depression, anxiety, and stress. Negative binomial regression was conudcted to study sociodemographic factors’ influence on the amount of practice in e-MBIs. ResultsThe participants with more diverse and sustained mindfulness practices experienced significant reductions in depression, anxiety, and stress. A high correlation (0.94) between e-MBI practices and symptom reduction was also highlighted. Male, married, and highly educated patients were more likely to engage in mindfulness. Even if DM and DSC did not impact the amount or variety of practices correlated, they were correlated with symptom reduction, showing that higher levels were associated with significant reductions in depression, anxiety, and stress. ConclusionsWhile more e-MBI practice is linked to reduced anxiety, depression, and stress, this study emphasizes the crucial role of variety of practice over amount. DM and DSC are key in shaping intervention effectiveness and may act as protectors against psychological distress. Using app log data, our research provides a unique perspective on e-MBI impact, contributing to cancer care understanding and guiding future studies.

El artículo analiza la coexistencia de las concesiones de Correo Mayor y las administraciones de correos en el Atlántico español. En Castilla las concesiones postales fueron extinguidas e incorporadas a la Corona después de 1700. Dentro de las Indias este proceso se dilató durante al menos medio siglo. Sin embargo, esto no fue un inconveniente para integrar circuitos ultramarinos y terrestres. Pretendo mostrar que, la situación legal de las concesiones de Correo Mayor en América, los costos de instalación y la dificultad de ofrecer un servicio postal equiparable al de los Habsburgo, provocaron la introducción de las administraciones de correos (indianas) por partes y a distintos ritmos.

IntroductionNeurosonology is a vital paraclinical investigation in modern neurology. However, access to education and certification in neurosonology for neurology residents and young specialists in Europe is challenging, and comprehensive data regarding this topic are scarce. Information regarding difficulties in neurosonology training across Europe may help bring this topic under the spotlight and act as a call for the harmonization of curricula across the continent.MethodsWe performed an online survey targeting European neurology residents and young specialists, focusing on neurosonology training and certification. The survey was conducted between May and September 2023 and received responses from 282 participants representing 37 European countries.ResultsThere were disparities in neurosonology training during residency, with 6 (16.2%) out of 37 countries reporting a dedicated curriculum. The respondents expressed an overall lack of satisfaction with theoretical knowledge (rating their experience as very poor 28.0%, poor 20.2%, neutral 25.9%, good 19.3%, and very good 6.6%) and practical skills gained during their training (rating their experience as very poor 30.9%, poor 18.9%, neutral 22.6%, good 18.1%, and very good 9.5%). A total of 282 respondents (5.7%), 16 held a national certification in neurosonology, claiming obstacles such as high costs of certification and a limited number of certifying centers.DiscussionThis survey reveals significant variations in neurosonology training across Europe, indicating difficulties in obtaining certification. Despite the increasing importance of neurosonology, many neurologists feel inadequately prepared and lack practical training during residency, emphasizing the need for better and more standardized access.ConclusionThe survey underscores challenges and disparities in neurosonology training and certification in Europe. Standardization of curricula and increased awareness about available certifications are crucial to address these issues. The interest in European Certification suggests a potential solution for enhancing neurosonology training at the international level.

Broilers are particularly sensitive to heat stress, which can impair growth, and lower conversion efficiency and survival rates. Under a climate change scenario, maintaining optimal thermal conditions within broiler houses becomes more complex and energy-intensive. Climate change can worsen air quality issues inside broiler houses by increasing the concentration of harmful gases, and proper mechanical ventilation systems are essential for diluting and removing these gases. The present study aimed to develop and validate a model for the ideal broiler housing strategy by applying the Paraconsistent Annotated Evidential Logic Eτ. A database from four broiler houses in a commercial farm, rearing 157,700 birds from the 1st to the 42nd day of growth, was used in the research. All environmental data were recorded weekly inside the houses, and on day 42, flock mortality, overall feed-to-gain ratio, and body weight were calculated and registered. The Cohen’s Kappa statistics for each environmental parameter classification compared to the paraconsistent classification. Results indicated that temperature shows good agreement, relative humidity shows slight agreement, air velocity presents a good agreement, CO2 concentration has a slight agreement, and NH3 concentration is classified by slight agreement. The environmental and productivity variables as a function of the broiler age using the extreme True paraconsistent state indicate the model validation. The paraconsistent analysis presented the ideal scenario for broilers’ growth, maintaining the environmental variables level within a particular threshold and providing greater profit to broiler farmers.

Seizures are common after severe traumatic brain injury (TBI), with rates in the acute period approaching 5% with seizure prophylaxis in historical clinical trials. Post-traumatic seizures (PTS) are divided into categories: immediate PTS occur prior to resuscitation, typically in the field; early PTS occur from resuscitation to 7 days post-trauma; and late PTS occur thereafter. The relationship between immediate and early PTS, as well as their risk factors, are not well studied in modern cohorts. We performed a secondary analysis of a prospective database of severe TBI patients, defined as a post-resuscitation Glasgow Coma Scale ?8, from a single institution. For the 579 patients included, rates of immediate and early PTS were 1.6% and 3.8%, respectively. We were unable to identify any clinical correlates for immediate seizures. In contrast, early PTS were associated with age (odds ratio [OR] 1.5; 95% confidence interval [CI]: 1.1?2.0; p?0.01), hypoxia (3.3, 95% CI: 1.2?8.5; p?=?0.02), and subdural hematoma (SDH) (2.8, 95% CI: 1.0?2.8; p?=?0.04) in multivariable modeling. Patients with early PTS had higher rates of status epilepticus than those with immediate PTS (45% [n?=?10/22] vs. 0% [n?=?0/9]; p?=?0.03). This supports the notion of immediate PTS, which typically occur in the field and may not reliably be deciphered from pathological posturing responses, as an entity distinct from early PTS. Status epilepticus was highly morbid, associated with a 70% mortality rate. Our previously identified markers may help risk-stratify patients who may warrant longer monitoring with continuous electroencephalography to detect and treat early PTS and corresponding status epilepticus risk.

Not available.

Revealing unknown cues that regulate oligodendrocyte progenitor cell (OPC) function in remyelination is important to optimise the development of regenerative therapies for multiple sclerosis (MS). Platelets are present in chronic non-remyelinated lesions of MS and an increase in circulating platelets has been described in experimental autoimmune encephalomyelitis (EAE) mice, an animal model for MS. However, the contribution of platelets to remyelination remains unexplored. Here we show platelet aggregation in proximity to OPCs in areas of experimental demyelination. Partial depletion of circulating platelets impaired OPC differentiation and remyelination, without altering blood-brain barrier stability and neuroinflammation. Transient exposure to platelets enhanced OPC differentiation in vitro, whereas sustained exposure suppressed this effect. In a mouse model of thrombocytosis (Calr+/-), there was a sustained increase in platelet aggregation together with a reduction of newly-generated oligodendrocytes following toxin-induced demyelination. These findings reveal a complex bimodal contribution of platelet to remyelination and provide insights into remyelination failure in MS.

Of the three types of waste generated in beer processing, brewer’s spent grain (BSG) is the most abundant and has a high potential for valorization. In this work, defatted BSG (DB) was subjected to an extraction process with subcritical water at different temperatures to obtain extracts rich in phenols and the cellulosic fractions, which were also purified by using hydrogen peroxide (H2O2). The results showed that the dry extracts obtained at 170 °C were richer in phenolics (24 mg Gallic Acid Equivalent (GAE) g−1 DB), but with lower antioxidant capacity (71 mg DB·mg−1 2,2-diphenyl-1-pikryl-hydrazyl). This extract also showed the highest antibacterial potential against L. innocua (80 mg·mL−1) and E. coli (140 mg·mL−1) than those obtained at lower temperatures. The purification of cellulose from the treated residues, using hydrogen peroxide, revealed that DB is a limited source of cellulose material since the bleached fractions showed low yields (20–25%) and low cellulose purity (42–71%), even after four bleaching cycles (1 h) at pH 12 and 8% H2O2. Despite this, the subcritical water extraction method highlights the potential of a simple process as a technological option to convert underutilized side streams like beer bagasse into added-value, potential ingredients for innovative food and pharmaceutical applications.

Abstract The primary motor (M1) and somatosensory (S1) cortices play critical roles in motor control but the signaling between these structures is poorly understood. To fill this gap, we recorded – in three participants in an ongoing human clinical trial (NCT01894802) for people with paralyzed hands – the responses evoked in the hand and arm representations of M1 during intracortical microstimulation (ICMS) in the hand representation of S1. We found that ICMS of S1 activated some M1 neurons at short, fixed latencies consistent with monosynaptic activation. Additionally, most of the ICMS-evoked responses in M1 were more variable in time, suggesting indirect effects of stimulation. The spatial pattern of M1 activation varied systematically: S1 electrodes that elicited percepts in a finger preferentially activated M1 neurons excited during that finger’s movement. Moreover, the indirect effects of S1 ICMS on M1 were context dependent, such that the magnitude and even sign relative to baseline varied across tasks. We tested the implications of these effects for brain-control of a virtual hand, in which ICMS conveyed tactile feedback. While ICMS-evoked activation of M1 disrupted decoder performance, this disruption was minimized using biomimetic stimulation, which emphasizes contact transients at the onset and offset of grasp, and reduces sustained stimulation.

Abstract The ability to perform sophisticated, high-throughput optogenetic experiments has been greatly enhanced by recent open-source illumination devices that allow independent programming of light patterns in single wells of microwell plates. However, there is currently a lack of instrumentation to monitor such experiments in real time, necessitating repeated transfers of the samples to stand-alone analytical instruments, thus limiting the types of experiments that could be performed. Here we address this gap with the development of the optoPlateReader (oPR), an open-source, solid-state, compact device that allows automated optogenetic stimulation and spectroscopy in each well of a 96-well plate. The oPR integrates an optoPlate illumination module with a module called the optoReader, an array of 96 photodiodes and LEDs that allows 96 parallel light measurements. The oPR was optimized for stimulation with blue light and for measurements of optical density and fluorescence. After calibration of all device components, we used the oPR to measure growth and to induce and measure fluorescent protein expression in E. coli. We further demonstrated how the optical read/write capabilities of the oPR permit computer-in-the-loop feedback control, where the current state of the sample can be used to adjust the optical stimulation parameters of the sample according to pre-defined feedback algorithms. The oPR will thus help realize an untapped potential for optogenetic experiments by enabling automated reading, writing, and feedback in microwell plates through open-source hardware that is accessible, customizable, and inexpensive.

Introduction: Previous studies have reported a correlation between a high-grade CMV-infection and an unfavorable prognosis in glioblastoma (GB). Coversely, epilepsy has been associated with a more favorable outcome in GB patients. Despites epilepsy and CMV share similar molecular mechanisms in GB tumoral microenvironment, the correlation between Tumor-Related-Epilepsy (TRE) and CMVinfection remains unexplored. The aim of our study is to examine the correlation between the dregree of CMV infection and seizure types on the survival of TRE Adult-type-diffuse-glioma. To achieve this objective, we conducted a comprehensive literature review to assess our results regarding previous publications Methods: We conducted a retrospective-observational study on TRE Adult-type-diffuse-gliomas treated at a single center in Mexico from 2010 to 2018. Tumor tissue and cDNA were analyzed by immunochemistry (IHC) for CMV (IE and LA antigens) at the Karolinska Institute in Sweden, and RT-PCR for CMV-gB in Torreon Mexico, respectively. Bivariate analysis (X2-test) was performed to evaluate the association between subtypes of Adult-type-diffuse-glioma (IDH-mut grade 4 astrocytoma vs. IDH-wt glioblastoma) and the following variables: type of hemispheric involvement (mesial vs. neocortical involvement), degree of CMV infection (25% infected-tumoral cells) and seizure types [Focal awareness, focal impaired awareness, and FBTCS]. Kaplan Meier and Cox analyses were performed to determine the risk, p

Background Paediatric HIV data shows a variable and sometimes catastrophic response in the initial stage of ART regimen administration. The burden of disease that affects children in their first year of treatment is not comprehensively available. Objective Objective of our study was to describe patterns of admission in children; before ART initiation, within the first six months, and post-six months of ART between 2001 and 2016. Methods Principal caregivers of 260 children (45.7% females 54.2% males, all

This paper deals with the stabilization of the linear biharmonic Schrödinger equation in an $n$-dimensional open bounded domain under Dirichlet–Neumann boundary conditions considering three infinite memory terms as damping mechanisms. We show that depending on the smoothness of initial data and the arbitrary growth at infinity of the kernel function, this class of solution goes to zero with a polynomial decay rate like $t^{-n}$ depending on assumptions about the kernel function associated with the infinite memory terms.

Abstract The aerobic granular biomass technology was optimized for treating nitrate-polluted groundwater based on the biological denitrification processes in order to provide drinking water. Reactors inoculated with granular biomass were operated at progressively lower C/N rate using acetate and methanol to encourage heterotrophic denitrification, in order to meet the recommended requirements described by European Drinking Water Framework Directive. The granulation and long-term stability of granular biomass under low C/N were successful for all stages, demonstrated compactness of granules and absence of filamentous microorganisms. The nitrate removal was similar in methanol- and acetate-fed reactors, occurring in both cases nitrate removal ratios > 80%, and fact allows the selection of one of both depending groundwater polluted case. Also, feeding reactors with 2 C/N ratio showed nitrate removal values of ≥ 95%, treating highly polluted groundwater (100 mg·L−1). The microbial diversity was higher in the methanol-fed reactor with representative phylotypes as Flavobacterium, Cytophagaceae, NS9 marine group, while species richness was higher in the acetate-fed reactor, which was mainly represented by Flavobacterium genus. Statistical analyses revealed the higher resilience of bacterial population on granules fed with acetate, showing more resistance under drop C/N ratio. Oscillating pollution in groundwater during seasonal periods should be treated using acetate as carbon source for denitrification carried out by granular biomass, while stable pollution concentrations over time allow the use of methanol as a carbon source since the greater microbial diversity allows the elimination of other contaminants present in groundwater.

Abstract Background Anti-CGRP monoclonal antibodies have shown notable effectiveness and tolerability in migraine patients; however, data on their use in elderly patients is still lacking, as clinical trials have implicit age restrictions and real-world evidence is scarce. In this study, we aimed to describe the safety and effectiveness of erenumab, galcanezumab and fremanezumab in migraine patients over 65 years old in real-life. Methods In this observational real-life study, a retrospective analysis of prospectively collected data from 18 different headache units in Spain was performed. Migraine patients who started treatment with any anti-CGRP monoclonal antibody after the age of 65 years were included. Primary endpoints were reduction in monthly migraine days after 6 months of treatment and the presence of adverse effects. Secondary endpoints were reductions in headache and medication intake frequencies by months 3 and 6, response rates, changes in patient-reported outcomes and reasons for discontinuation. As a subanalysis, reduction in monthly migraine days and proportion of adverse effects were also compared among the three monoclonal antibodies. Results A total of 162 patients were included, median age 68 years (range 65–87), 74.1% women. 42% had dyslipidaemia, 40.3% hypertension, 8% diabetes, and 6.2% previous cardiovascular ischaemic disease. The reduction in monthly migraine days at month 6 was 10.1 ± 7.3 days. A total of 25.3% of patients presented adverse effects, all of them mild, with only two cases of blood pressure increase. Headache and medication intake frequencies were significantly reduced, and patient-reported outcomes were improved. The proportions of responders were 68%, 57%, 33% and 9% for reductions in monthly migraine days ≥ 30%, ≥ 50%, ≥ 75% and 100%, respectively. A total of 72.8% of patients continued with the treatment after 6 months. The reduction in migraine days was similar for the different anti-CGRP treatments, but fewer adverse effects were detected with fremanezumab (7.7%). Conclusions Anti-CGRP mAbs are safe and effective treatments in migraine patients over 65 years old in real-life clinical practice. Graphical Abstract

Abstract Background Multiple sclerosis (MS) is a chronic demyelinating autoimmune disorder which may cause long-term disability. MicroRNA (miRNA) are stable, non-coding molecules that have been identified in our Comprehensive Longitudinal Investigation of Multiple Sclerosis at the Brigham and Women’s Hospital (CLIMB)-cohort, as well as other international cohorts, as potential disease biomarkers in MS. However, few studies have evaluated the association of miRNA expression early in the MS disease course with long-term outcomes. Therefore, we aimed to evaluate the potential role of three candidate serum miRNAs previously correlated with MS disability in patients with MS, miR-320b, miR-25-3p and miRNA 486-5p, as early biomarkers of MS disability at 10-year follow-up. Main body We included 144 patients with serum obtained within three years of MS onset. miRNA expression was measured by RNA extraction followed by RT-PCR. Demographic, clinical, brain MRI and other biomarkers were collected. The primary outcome was the association between early miRNA expression and retaining benign MS, defined as EDSS ≤ 2 at 10-year follow-up. Among the 144 patients, 104 were benign and 40 were not benign at 10-year follow-up. 89 (62%) were women, with mean age at onset 37.7 (SD: 9.6) years. Patients who retained benign MS had lower values of miR-25-3p (p = 0.047) and higher miR-320b (p = 0.025) values. Development of SPMS was associated with higher miR-320b (p = 0.002) levels. Brain parenchymal fraction at year 10 was negatively correlated with miR-25-3p (p = 0.0004) and positively correlated with miR-320b (p = 0.006). No association was found between miR-486-5p and any outcome, and 10-year T2-lesion volume was not associated with any miRNA. Conclusions Our results show that miR-320b and miR-25-3p expression are early biomarkers associated with MS severity and brain atrophy. This study provides class III evidence of that miR-320b and miR-25-3p are associated with long-term MS disability which may be a potential tool to risk-stratify patients with MS for early treatment decisions.

Capacitive humidity sensors typically consist of interdigitated electrodes coated with a dielectric layer sensitive to varying relative humidity levels. Previous studies have investigated different polymeric materials that exhibit changes in conductivity in response to water vapor to design capacitive humidity sensors. However, lipid films like monoolein have not yet been integrated with humidity sensors, nor has the potential use of capacitive sensors for skin hydration measurements been fully explored. This study explores the application of monoolein-coated wireless capacitive sensors for assessing relative humidity and skin hydration, utilizing the sensitive dielectric properties of the monoolein–water system. This sensitivity hinges on the water absorption and release from the surrounding environment. Tested across various humidity levels and temperatures, these novel double functional sensors feature interdigitated electrodes covered with monoolein and show promising potential for wireless detection of skin hydration. The water uptake and rheological behavior of monoolein in response to humidity were evaluated using a quartz crystal microbalance with dissipation monitoring. The findings from these experiments suggest that the capacitance of the system is primarily influenced by the amount of water in the monoolein system, with the lyotropic or physical state of monoolein playing a secondary role. A proof-of-principle demonstration compared the sensor’s performance under varying conditions to that of other commercially available skin hydration meters, affirming its effectiveness, reliability, and commercial viability.

The European Cooperation in Science and Technology (COST) is an intergovernmental organization dedicated to funding and coordinating scientific and technological research in Europe, fostering collaboration among researchers and institutions across countries. Recently, COST Action funded the ''Genome Editing to treat Human Diseases'' (GenE-HumDi) network, uniting various stakeholders such as pharmaceutical companies, academic institutions, regulatory agencies, biotech firms, and patient advocacy groups. GenE-HumDi’s primary objective is to expedite the application of genome editing for therapeutic purposes in treating human diseases. To achieve this goal, GenE-HumDi is organized in several working groups, each focusing on specific aspects. These groups aim to enhance genome editing technologies, assess delivery systems, address safety concerns, promote clinical translation, and develop regulatory guidelines. The network seeks to establish standard procedures and guidelines for these areas to standardize scientific practices and facilitate knowledge sharing. Furthermore, GenE-HumDi aims to communicate its findings to the public in accessible yet rigorous language, emphasizing genome editing’s potential to revolutionize the treatment of many human diseases. The inaugural GenE-HumDi meeting, held in Granada, Spain, in March 2023, featured presentations from experts in the field, discussing recent breakthroughs in delivery methods, safety measures, clinical translation, and regulatory aspects related to gene editing.

Purpose: To report a patient with a unilateral presentation of glaucoma, pain, and acute iris transillumination syndrome simulating iris melanoma. Observations: A 53-year-old male presented with blurred vision and pain in his right eye several weeks following a respiratory sinus infection managed by oral azithromycin. Examination of the right eye was notable for elevated intraocular pressure of 46 mm Hg, an irregular mid-dilated pupil, and diffuse iris transillumination with pigmentary seeding on the iris surface, in the anterior chamber angle, and on the sclera, suspicious for diffuse iris melanoma with glaucoma and extrascleral extension. Ultrasound biomicroscopy (UBM) of the right eye revealed circumferential anterior chamber angle and trabecular meshwork involvement by an infiltrative process corresponding to the pigmented cells noted clinically, while the ciliary body was unremarkable. Following enucleation, histopathology showed extensive necrosis of the iris pigment epithelium, sphincter, and dilator muscles with melanophagic infiltration in the anterior chamber angle and episclera, mild chronic non-granulomatous iridocyclitis, and no evidence of a melanocytic neoplasm. Although immunohistochemical studies for herpes simplex virus (HSV) types 1 and 2, varicella-zoster virus, and cytomegalovirus were negative, qualitative real-time polymerase chain reaction on paraffin-embedded tissue detected HSV-1 DNA. The combined clinical, pathologic, and molecular findings were compatible with unilateral acute iris transillumination syndrome, likely HSV-1 associated. Conclusion and Importance: Unilateral acute iris transillumination syndrome with diffuse iris pigment epithelial loss can simulate iris melanoma. Prompt herpes viral studies may be informative.

Abstract Background Multiple sclerosis (MS) is a disabling autoimmune demyelinating disorder affecting young people and causing significant disability. In the last decade, different microRNA (miRNA) expression patterns have been associated to several treatment response therapies such as interferon and glatiramer acetate. Nowadays, there is increasing interest in the potential role of miRNA as treatment response biomarkers to the most recent oral and intravenous treatments. In this study, we aimed to evaluate serum miRNAs as biomarkers of No Evidence of Disease Activity (NEDA-3) at 2 years in patients with relapsing remitting MS (RRMS) treated with fingolimod. Main body A Discovery cohort of 31 RRMS patients treated with fingolimod were identified from the CLIMB study and classified as No Evidence of Disease Activity (NEDA-3) or Evidence of Disease Activity (EDA-3) after 2 years on treatment. Levels of miRNA expression were measured at 6 months using human serum miRNA panels and compared in EDA-3 and NEDA-3 groups using the Wilcoxon rank sum test. A set of differentially expressed miRNA was further validated in an independent cohort of 22 fingolimod-treated patients. We found that 548a-3p serum levels were higher levels in fingolimod-treated patients classified as NEDA-3, compared to the EDA-3 group in both the Discovery (n = 31; p = 0.04) and Validation (n = 22; p = 0.03) cohorts 6 months after treatment initiation; miR-548a-3p provided an AUC of 0.882 discriminating patients with NEDA-3 at 2 years in the Validation cohort. Conclusion Our results show differences in miR-548a-3p expression at 6 months after fingolimod start in patients with MS with NEDA-3 at 2 years. These results provide class III evidence of the use of miR-548a-3p as biomarker of NEDA-3 in patients with fingolimod.

Abstract The recent discovery of the potential of jet quenching observables to constrain the initial stages after a heavy-ion collision makes imperative to have a better understanding of the process of medium-induced radiation before the formation of the quark-gluon plasma (QGP) and its impact on observables at high-p T . In this work, we generalize the BDMPS-Z framework for medium-induced radiation to account for additional emissions occurring before the creation of the QGP. For simplicity, we assume that during the pre-hydrodynamics phase the hard parton propagates as in vacuum. This set-up, allows us to isolate the contribution from the additional initial radiation by comparing with the usual scenarios in which the emitter is created inside the medium but with different starting points. Using both a numerical implementation of the fully resummed emission spectrum and the usual analytical approximations, we find that replacing an initial slab of the medium by vacuum yields to a significant reduction of the emission spectrum for low radiated gluon energies, while the high-energy tails remain largely unmodified. Finally, we assess the effect of replacing the initial medium by vacuum propagation on the single-inclusive particle suppression R AA and high-p T azimuthal asymmetry v 2. Our findings indicate that considering vacuum propagation prior to hydrodynamization leads to an increase in the v 2, thus corroborating the importance of the treatment of jet quenching in the initial stages for the correct description of both observables.

BackgroundeHealth systems have been increasingly used to manage depressive symptoms in patients with somatic illnesses. However, understanding the factors that drive their use, particularly among patients with breast and prostate cancer, remains a critical area of research. ObjectiveThis study aimed to determine the factors influencing use of the NEVERMIND eHealth system among patients with breast and prostate cancer over 12 weeks, with a focus on the Technology Acceptance Model. MethodsData from the NEVERMIND trial, which included 129 patients with breast and prostate cancer, were retrieved. At baseline, participants completed questionnaires detailing demographic data and measuring depressive and stress symptoms using the Beck Depression Inventory–II and the Depression, Anxiety, and Stress Scale–21, respectively. Over a 12-week period, patients engaged with the NEVERMIND system, with follow-up questionnaires administered at 4 weeks and after 12 weeks assessing the system’s perceived ease of use and usefulness. Use log data were collected at the 2- and 12-week marks. The relationships among sex, education, baseline depressive and stress symptoms, perceived ease of use, perceived usefulness (PU), and system use at various stages were examined using Bayesian structural equation modeling in a path analysis, a technique that differs from traditional frequentist methods. ResultsThe path analysis was conducted among 100 patients with breast and prostate cancer, with 66% (n=66) being female and 81% (n=81) having a college education. Patients reported good mental health scores, with low levels of depression and stress at baseline. System use was approximately 6 days in the initial 2 weeks and 45 days over the 12-week study period. The results revealed that PU was the strongest predictor of system use at 12 weeks (βuse at 12 weeks is predicted by PU at 12 weeks=.384), whereas system use at 2 weeks moderately predicted system use at 12 weeks (βuse at 12 weeks is predicted by use at 2 weeks=.239). Notably, there were uncertain associations between baseline variables (education, sex, and mental health symptoms) and system use at 2 weeks, indicating a need for better predictors for early system use. ConclusionsThis study underscores the importance of PU and early engagement in patient engagement with eHealth systems such as NEVERMIND. This suggests that, in general eHealth implementations, caregivers should educate patients about the benefits and functionalities of such systems, thus enhancing their understanding of potential health impacts. Concentrating resources on promoting early engagement is also essential given its influence on sustained use. Further research is necessary to clarify the remaining uncertainties, enabling us to refine our strategies and maximize the benefits of eHealth systems in health care settings.

Managing Multi-Processor Systems-on-Chip (MPSoCs) is becoming increasingly complex as demands for advanced capabilities rise. This complexity is due to the involvement of more processing elements and resources, leading to a higher degree of heterogeneity throughout the system. Over time, management schemes have evolved from simple to autonomous systems with continuous control and monitoring of various parameters such as power distribution, thermal events, fault tolerance, and system security. Autonomous management integrates self-awareness into the system, making it aware of its environment, behavior, and objectives. Self-Aware Cyber-Physical Systems-on-Chip (SA-CPSoCs) have emerged as a concept to achieve highly autonomous management. Communication infrastructure is also vital to SoCs, and Software-Defined Networks-on-Chip (SDNoCs) can serve as a base structure for self-aware systems-on-chip. This paper presents a survey of the evolution of MPSoC management over the last two decades, categorizing research works according to their objectives and improvements. It also discusses the characteristics and properties of SA-CPSoCs and explains why SDNoCs are crucial for these systems.

Human papillomavirus (HPV) is a known cause of cervical cancer. Here, the authors perform a multi-omic analysis using published cervical squamous cell carcinoma cohorts from the USA, Europe, and SubSaharan Africa and identify two cervical squamous cell carcinoma subtypes that display prognostic differences.

Aim of study: To characterize and compare the genetic resources and gain some insights into the evolutionary history of Aleppo pine (Pinus halepensis Mill.) and Brutia pine (Pinus brutia Ten.) species which are both distributed across more than 8 million hectares of area in the Mediterranean Basin. Study area: Fifty-six populations from eight Mediterranean basin countries where P. halepensis and P. brutia species are located. Materials and methods: We analyzed 1344 seeds belonging to 56 populations using five cpSSR primers (Pt15169, Pt30204, Pt41093, Pt87268, and Pt110048). Main results: The analysis of molecular variance (AMOVA) revealed that the genetic diversity among the Brutia pine populations was slightly higher than that of Aleppo pine (27.06% and 24.27%, respectively). The Aleppo pine populations separately displayed a clear east-west differentiation across the Mediterranean Basin, confirming previous results using other markers. Although the Brutia pine populations showed no spatial genetic pattern, geographically close populations and/or populations from their continual distribution range were genetically closer than the fragmented and/or ecologically marginal populations. Research highlights: The seven Aleppo pine populations from the eastern range (Türkiye, Greece, and Italy) were more than two-fold diverse than the 13 populations from the western range (Spain and Morocco). The eastern range of Aleppo pine and Brutia pine populations had similar levels of genetic diversity parameters. These results suggested that the Eastern Mediterranean Basin is a possible genetic diversity center for the two pine species.

In this manuscript, we analyze the exponential stability of a strongly coupled semilinear system of Klein-Gordon type, posed in an inhomogeneous medium Ω\Omega , subject to local dampings of different natures distributed around a neighborhood of the boundary according to the geometric control condition (GCC). The first one is of the type viscoelastic and is distributed around a neighborhood ω\omega of the boundary ∂Ω\partial \Omega of Ω\Omega , according to the GCC. The second one is a frictional damping and we consider it hurting the GCC. The third dissipation, which acts only in the second equation (according to the GCC), is of the frictional type. We show that the energy of the system goes uniformly and exponentially to zero for all initial data of finite energy taken in bounded sets of finite energy phase space. We also prove the exponential decay for the linear problem associated with this same system, and in this case, no restrictions are made with respect to dimension of the space nor with respect to the limitation of the initial data in the phase space.

Abstract Atomic Force Microscopy (AFM) force measurements are a powerful tool for the nano-scale characterization of surface properties. However, the analysis of force measurements requires several processing steps. One is locating different type of events e.g., contact point, adhesions and indentations. At present, there is a lack of algorithms that can automate this process in a reliable way for different types of samples. Moreover, because of their stochastic nature, the acquisition and analysis of a high number of force measurements is typically required. This can result in these experiments becoming an overwhelming task if their analysis is not automated. Here, we propose a Machine Learning approach, the use of one-dimensional convolutional neural networks, to locate specific events within AFM force measurements. Specifically, we focus on locating the contact point, a critical step for the accurate quantification of mechanical properties as well as long-range interactions. We validate this approach on force measurements obtained both on hard and soft surfaces. This approach, which could be easily used to also locate other events e.g., indentations and adhesions, has the potential to significantly facilitate and automate the analysis of AFM force measurements and, therefore, the use of this technique by a wider community.

Abstract Background We investigated risk factors for sustained virological non-suppression (viral load ≥ 1000 copies/ml on two tests 48 weeks apart) among children and adolescents accessing HIV care in public sector clinics in Harare, Zimbabwe and Blantyre, Malawi. Methods Participants were enrolled between 2016 and 2019, were aged 6–19 years, living with HIV, had chronic lung disease (FEV z-score

Nowadays, the discharge of wastewater is a global concern due to the damage caused to human and environmental health. Wastewater treatment has progressed to provide environmentally and economically sustainable technologies. The biological treatment of wastewater is one of the fundamental bases of this field, and the employment of new technologies based on granular biofilm systems is demonstrating success in tackling the environmental issues derived from the discharge of wastewater. The granular-conforming microorganisms must be evaluated as functional entities because their activities and functions for removing pollutants are interconnected with the surrounding microbiota. The deep knowledge of microbial communities allows for the improvement in system operation, as the proliferation of microorganisms in charge of metabolic roles could be modified by adjustments to operational conditions. This is why engineering must consider the intrinsic microbiological aspects of biological wastewater treatment systems to obtain the most effective performance. This review provides an extensive view of the microbial ecology of biological wastewater treatment technologies based on granular biofilms for mitigating water pollution.

Broiler meat is one of the most consumed meats worldwide. The broiler production system poses several challenges for the producer, including maintaining environmental conditions for rearing. The popularization of mobile devices (smartphones) among people, including those with lower incomes, makes it possible for specialist systems to be developed and used for diverse purposes through Apps (mobile application). The present study proposed the development of a mobile application to help farmers follow up on-farm flock management. We retrieved rearing environment and flock data from commercial broiler farms that complied with broiler-producing standards and followed the breeders’ recommendations. Data were organized and normalized to serve as the basis for the software. We specified a performance index based on the average environment and flock-based data. The language used for the application development was Python compatible with the GNU GPL (General Public License), which has a vast library of ready-made functions. For the graphical interface, we selected Kivy and KivyMD framework. The developed mobile application might help farmers evaluate broiler rearing conditions on-farm during the flock’s growth and grade the flock using a performance index.

Abstract The ability to provide high sensitivity with small footprints makes miniaturized electrodes key components of biosensing, wearable electronics and lab‐on‐a‐chip devices. Recently, thin film deposition onto polystyrene films, followed by thermal shrinking has been used to produce microstructured electrodes (MSEs) with high electroactive surface area (ESA). Nevertheless, the high cost associated with film deposition through evaporation used in microfabrication and the variability in performance of screen‐printed electrodes (SPEs) remain key barriers that limit their widespread deployment. Here, a simple and inexpensive method is developed for the solution‐based patterning of high‐quality metallic films on polystyrene substrates for MSE fabrication. The ESA of electrodes produced through this method is 2 × and 12 × larger than that of microstructured and planar electrodes produced through sputtering, respectively, and their cost is only 20% of sputtered ones. This methodology allows the fabrication of on‐chip microstructured electrochemical cells (SMECs) with excellent analytical performance (3% RSD inter‐day reproducibility and 0.3% RSD repeatability), superior to that of commercially available SPEs. In addition, the ESA of SMECs is significantly higher than that of SPEs, and they show excellent response toward dopamine detection. We anticipate that this solution‐based fabrication approach will expedite the development of miniaturized sensing platforms for point‐of‐care applications.

Abstract Objective Stereotactic electroencephalography (SEEG) has been widely used to explore the epileptic network and localize the epileptic zone in patients with medically intractable epilepsy. Accurate anatomical labeling of SEEG electrode contacts is critically important for correctly interpreting epileptic activity. We present a method for automatically assigning anatomical labels to SEEG electrode contacts using a 3D‐segmented cortex and coregistered postoperative CT images. Method Stereotactic electroencephalography electrode contacts were spatially localized relative to the brain volume using a standard clinical procedure. Each contact was then assigned an anatomical label by clinical epilepsy fellows. Separately, each contact was automatically labeled by coregistering the subject's MRI to the USCBrain atlas using the BrainSuite software and assigning labels from the atlas based on contact locations. The results of both labeling methods were then compared, and a subsequent vetting of the anatomical labels was performed by expert review. Results Anatomical labeling agreement between the two methods for over 17 000 SEEG contacts was 82%. This agreement was consistent in patients with and without previous surgery (P = .852). Expert review of contacts in disagreement between the two methods resulted in agreement with the atlas based over manual labels in 48% of cases, agreement with manual over atlas‐based labels in 36% of cases, and disagreement with both methods in 16% of cases. Labels deemed incorrect by the expert review were then categorized as either in a region directly adjacent to the correct label or as a gross error, revealing a lower likelihood of gross error from the automated method. Significance The method for semi‐automated atlas‐based anatomical labeling we describe here demonstrates potential to assist clinical workflow by reducing both analysis time and the likelihood of gross anatomical error. Additionally, it provides a convenient means of intersubject analysis by standardizing the anatomical labels applied to SEEG contact locations across subjects.

Abstract Surfactants are important components of oral care products. Sodium dodecyl sulfate (SDS) is the most common because of its foaming properties, taste and low cost. However, the use of ionic surfactants, especially SDS, is related to several oral mucosa conditions. Thus, there is a high interest in using non-ionic and amphoteric surfactants as they are less irritant. To better understand the performance of these surfactants in oral care products, we investigated their interaction with salivary pellicles i.e., the proteinaceous films that cover surfaces exposed to saliva. Specifically, we focused on pentaethylene glycol monododecyl ether (C12E5) and cocamidopropyl betaine (CAPB) as model nonionic and amphoteric surfactants respectively, and investigated their interaction with reconstituted salivary pellicles with various surface techniques: Quartz Crystal Microbalance with Dissipation, Ellipsometry, Force Spectroscopy and Neutron Reflectometry. Both C12E5 and CAPB were gentler on pellicles than SDS, removing a lower amount. However, their interaction with pellicles differed. Our work indicates that CAPB would mainly interact with the mucin components of pellicles, leading to collapse and dehydration. In contrast, exposure to C12E5 had a minimal effect on the pellicles, mainly resulting in the replacement/solubilisation of some of the components anchoring pellicles to their substrate.

Amorpha californica var. napensis Jeps. 1925, the Napa false indigo, is a threatened shrub endemic to northern California. Here the complete chloroplast genome of topotype material of var. napensis was assembled and characterized to contribute to the bioinformatics, systematics, and conservation of this variety. The chloroplast genome (GenBank accession OK274088) is 158,294 base pairs (bp) in length, encodes 130 genes including 85 protein-coding, 37 tRNA, 8 rRNA, and shows a high-level of gene synteny to other Papilionoideae. Phylogenetic analysis fully resolved var. napensis in a clade with A. fruticosa L. and A. roemeriana Scheele, sister to the Dalbergieae. The newly sequenced chloroplast genome shows that the genetic differences between var. napensis and Amorpha californica Nutt. var. californica are greater than the variation observed between var. napensis and many other Amorpha spp. sequences deposited in GenBank. These data suggest that var. napensis should be elevated to full species rank.

Aß are extracellular deposits relevant in Alzheimer’s disease (AD). This study shows that Aß plaques are hubs of endothelial disassembly that induce non-productive angiogenesis. This process is aided by the microglia and unchained by reduced presenilin function, a trait of AD, in endothelial cells.

Abstract A proper understanding of the physics of medium-induced gluon emissions is known to be of critical importance to describe the properties of strongly interacting matter under extreme conditions. In this regard, many theoretical efforts have been directed towards obtaining analytical calculations which might help us discerning the underlying physical picture and the dominant dynamics for different regimes. These analytical approaches rely on approximations whose validity is analyzed here by comparing their results with a recently developed numerical evaluation which includes all-order resummation of multiple scatterings. More specifically, by quantitatively comparing the energy spectrum and rates, we observe that three different regimes — each with its corresponding physical picture — emerge naturally from the equations: the high-energy regime where the emission process is dominated by a single hard scattering, the intermediate-energy regime where coherence effects among multiple scatterings become fundamental, and the low-energy regime where the dynamics is again dominated by a single scattering but where one must include the suppression factor due to the probability of not having any further scatterings (which is obtained through the resummation of virtual terms).

Summary: Background: This study assessed the effectiveness of the NEVERMIND e-health system, consisting of a smart shirt and a mobile application with lifestyle behavioural advice, mindfulness-based therapy, and cognitive behavioural therapy, in reducing depressive symptoms among patients diagnosed with severe somatic conditions. Our hypothesis was that the system would significantly decrease the level of depressive symptoms in the intervention group compared to the control group. Methods: This pragmatic, randomised controlled trial included 425 patients diagnosed with myocardial infarction, breast cancer, prostate cancer, kidney failure, or lower limb amputation. Participants were recruited from hospitals in Turin and Pisa (Italy), and Lisbon (Portugal), and were randomly assigned to either the NEVERMIND intervention or to the control group. Clinical interviews and structured questionnaires were administered at baseline, 12 weeks, and 24 weeks. The primary outcome was depressive symptoms at 12 weeks measured by the Beck Depression Inventory II (BDI-II). Intention-to-treat analyses included 425 participants, while the per-protocol analyses included 333 participants. This trial is registered in the German Clinical Trials Register, DRKS00013391. Findings: Patients were recruited between Dec 4, 2017, and Dec 31, 2019, with 213 assigned to the intervention and 212 to the control group. The sample had a mean age of 59·41 years (SD=10·70), with 44·24% women. Those who used the NEVERMIND system had statistically significant lower depressive symptoms at the 12-week follow-up (mean difference=-3·03, p

BackgroundeHealth interventions have become a topic of interest in the field of mental health owing to their increased coordination and integration of different elements of care, in treating and preventing mental ill health in patients with somatic illnesses. However, poor usability, learnability, and user engagement might affect the effectiveness of an eHealth intervention. Identifying different sociodemographic characteristics that might be associated with higher perceived usability can help improve the usability of eHealth interventions. ObjectiveThis study aimed to identify the sociodemographic characteristics that might be associated with the perceived usability of the NEVERMIND (Neurobehavioural Predictive and Personalised Modelling of Depressive Symptoms During Primary Somatic Diseases) eHealth system, comprising a mobile app and a sensorized shirt, in reducing comorbid depressive symptoms in patients with breast or prostate cancer. MethodsThe study included a total of 129 patients diagnosed with breast (n=80, 62%) or prostate (n=49, 38%) cancer, who received a fully automated mobile app and sensorized shirt (NEVERMIND system). Sociodemographic data on age, sex, marital status, education level, and employment status were collected at baseline. Usability outcomes included the System Usability Scale (SUS), a subjective measure that covers different aspects of system usability; the user version of the Mobile App Rating Scale (uMARS), a user experience questionnaire; and a usage index, an indicator calculated from the number of days patients used the NEVERMIND system during the study period. ResultsThe analysis was based on 108 patients (n=68, 63%, patients with breast cancer and n=40, 37%, patients with prostate cancer) who used the NEVERMIND system for an average of 12 weeks and completed the study. The overall mean SUS score at 12 weeks was 73.4 (SD 12.5), which indicates that the NEVERMIND system has good usability, with no statistical differences among different sociodemographic characteristics. The global uMARS score was 3.8 (SD 0.3), and women rated the app higher than men (β=.16; P=.03, 95% CI 0.02-0.3), after adjusting for other covariates. No other sociodemographic characteristics were associated with higher uMARS scores. There was a statistical difference in the use of the NEVERMIND system between women and men. Women had significantly lower use (β=–0.13; P=.04, 95% CI −0.25 to −0.01), after adjusting for other covariates. ConclusionsThe findings suggest that the NEVERMIND system has good usability according to the SUS and uMARS scores. There was a higher favorability of mobile apps among women than among men. However, men had significantly higher use of the NEVERMIND system. Despite the small sample size and low variability, there is an indication that the NEVERMIND system does not suffer from the digital divide, where certain sociodemographic characteristics are more associated with higher usability. Trial RegistrationGerman Clinical Trials Register RKS00013391; https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00013391

Abstract Chronic migraine is a neurological disorder characterized by 15 or more headache days per month of which at least 8 days show typical migraine features. The process that describes the development from episodic migraine into chronic migraine is commonly referred to as migraine transformation or chronification. Ample studies have attempted to identify factors associated with migraine transformation from different perspectives. Understanding CM as a pathological brain state with trigeminovascular participation where biological changes occur, we have completed a comprehensive review on the clinical, epidemiological, genetic, molecular, structural, functional, physiological and preclinical evidence available.

Abstract Background Depressive symptoms are common in individuals suffering from severe somatic conditions. There is a lack of interventions and evidence-based interventions aiming to reduce depressive symptoms in patients with severe somatic conditions. The aim of the NEVERMIND project is to address these issues and provide evidence by testing the NEVERMIND system, designed to reduce and prevent depressive symptoms in comparison to treatment as usual. Methods The NEVERMIND study is a parallel-groups, pragmatic randomised controlled trial to assess the effectiveness of the NEVERMIND system in reducing depressive symptoms among individuals with severe somatic conditions. The NEVERMIND system comprises a smart shirt and a user interface, in the form of a mobile application. The system is a real-time decision support system, aiming to predict the severity and onset of depressive symptoms by modelling the well-being condition of patients based on physiological data, body movement, and the recurrence of social interactions. The study includes 330 patients who have a diagnosis of myocardial infarction, breast cancer, prostate cancer, kidney failure, or lower limb amputation. Participants are randomised in blocks of ten to either the NEVERMIND intervention or treatment as usual as the control group. Clinical interviews and structured questionnaires are administered at baseline, at 12 weeks, and 24 weeks to assess whether the NEVERMIND system is superior to treatment as usual. The endpoint of primary interest is Beck Depression Inventory II (BDI-II) at 12 weeks defined as (i) the severity of depressive symptoms as measured by the BDI-II. Secondary outcomes include prevention of the onset of depressive symptoms, changes in quality of life, perceived stigma, and self-efficacy. Discussion There is a lack of evidence-based interventions aiming to reduce and prevent depressive symptoms in patients with severe somatic conditions. If the NEVERMIND system is effective, it will provide healthcare systems with a novel and innovative method to attend to depressive symptoms in patients with severe somatic conditions. Trial registration DRKS00013391 . Registered 23 November 2017.

The structure and function of epithelial cells are critical for the construction and maintenance of intact epithelial surfaces throughout the body. Beyond the mechanical barrier functions, epithelial cells have been identified as active participants in providing warning signals to the host immune and inflammatory cells and in communicating various detailed information on the noxious challenge to help drive specificity in the characteristics of the host response related to health or pathologic inflammation. Rhesus monkeys were used in these studies to evaluate the gingival transcriptome for naturally occurring disease samples (GeneChip® Rhesus Macaque Genome Array) or for ligature-induced disease (GeneChip® Rhesus Gene 1.0 ST Array) to explore up to 452 annotated genes related to epithelial cell structure and functions. Animals were distributed by age into four groups: ≤ 3 years (young), 3–7 years (adolescent), 12–16 years (adult), and 18–23 years (aged). For naturally occurring disease, adult and aged periodontitis animals were used, which comprised 34 animals (14 females and 20 males). Groups of nine animals in similar age groups were included in a ligature-induced periodontitis experiment. A buccal gingival sample from either healthy or periodontitis-affected tissues were collected, and microarray analysis performed. The overall results of this investigation suggested a substantial alteration in epithelial cell functions that occurs rapidly with disease initiation. Many of these changes were prolonged throughout disease progression and generally reflect a disruption of normal cellular functions that would presage the resulting tissue destruction and clinical disease measures. Finally, clinical resolution may not signify biological resolution and represent a continued risk for disease that may require considerations for additional biologically specific interventions to best manage further disease.