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Abstract The presence of somatic mutations, including copy number variants (CNVs), in the brain is well recognized. Comprehensive study requires single-cell whole genome amplification, with several methods available, prior to sequencing. Here we compare PicoPLEX with two recent adaptations of multiple displacement amplification (MDA): primary template-directed amplification (PTA) and droplet MDA, across 93 human brain cortical nuclei. We demonstrate different properties for each, with PTA providing the broadest amplification, PicoPLEX the most even, and distinct chimeric profiles. Furthermore, we perform CNV calling on two brains with multiple system atrophy and one control brain using different reference genomes. We find that 20.6% of brain cells have at least one Mb-scale CNV, with some supported by bulk sequencing or single-cells from other brain regions. Our study highlights the importance of selecting whole genome amplification method and reference genome for CNV calling, while supporting the existence of somatic CNVs in healthy and diseased human brain.

Autosomal-dominant polycystic kidney disease (ADPKD) is the most common inherited kidney disease and fourth leading cause for renal replacement therapy worldwide. Disease progression is tightly linked to genotype, however, factors like genetic modifiers and environmental factors are responsible for a high phenotypic variability within- as well as between families. Individual’s risk of progression to kidney failure is assessed using prediction- or risk-assessment tools such as the predicting renal outcomes in ADPKD score (PROPKD score) and the Mayo Imaging Classification (MIC). The PROPKD score encompasses genetic and phenotypic parameters, while the MIC relies on renal imaging, height, and age of patients. Both methods categorize patients into low-risk, intermediate-risk, and high-risk for progression to kidney failure. In this retrospective, cross-sectional study, we calculated the risk of progression to kidney failure in our population and analyzed the agreement between the methods in three separate models with alternating stratification of MIC risk categories. We found a mismatch for risk assessment between the respective risk categories, indicating that the PROPKD score and MIC should not be used interchangeably. Preferably, the MIC should be used as a base for risk assessment and may be enhanced by genotypic and phenotypic information.

The scattering of light by polymeric nanoparticles is a crucial phenomenon in various applications, ranging from nanomedicine to nanophononics. This study introduces a theoretical framework for differentiating between absorption and scattering spectra in light interactions with these nanoparticles. Characteristic spectral data of nanoparticles synthesized via the reprecipitation method and suspended in an aqueous medium analyzed under electromagnetic radiation. These nanoparticles exhibit two primary optical phenomena: absorption and scattering. To fully understand their optical response, it is essential to separate these phenomena. This study established a relationship between wavelength variation, nanoparticle size, and radiation loss due to scattering in an aqueous medium. Additionally, we calculated extinction efficiency and extinction factors as functions of wavelength, taking into account variations in nanoparticle radii and refractive indices.

The present research studied the relationship between the credentials of teachers and the academic performance of students who, in the 2014–2015 period, joined the bachelor’s degree program in Economics at the Universidad Católica Andrés Bello, Caracas, Venezuela. The hypothesis of a direct relationship between teaching quality and student performance was evaluated using a panel data methodology, in which the students were considered as “individuals,” and the semesters of the degree course were the time period under study. For the fixed and random effects estimations without instrumental variables, the following were found to be significant: the teacher’s marital status, place of study, pedagogical training, student evaluation, and the teacher’s professional commitments outside the academic sphere. The results do not allow us to accept the null hypothesis since academic teaching credentials do not promote significant increases in academic performance.

Abstract Background Reduction of the particle size of corn increases energy digestibility and concentrations of digestible and metabolizable energy. Pelleting may also reduce particle size of grain, but it is not known if there are interactions between particle size reduction and pelleting. The objective of this experiment was to test the hypothesis that particle size reduction and pelleting, separately or in combination, increase N balance, apparent total tract digestibility (ATTD) of fiber and fat, and net energy (NE) in corn-soybean meal diets fed to group-housed pigs. Methods Six corn-soybean meal-based diets were used in a 3 × 2 factorial design with 3 particle sizes of corn (i.e., 700, 500, or 300 μm) and 2 diet forms (i.e., meal or pelleted). Pigs were allowed ad libitum access to feed and water. Twenty-four castrated male pigs (initial weight: 29.52 kg; standard diviation: 1.40) were allotted to the 6 diets using a 6 × 6 Latin square design with 6 calorimeter chambers (i.e., 4 pigs/chamber) and 6 periods. Oxygen consumption and CO2 and CH4 productions were measured during fed and fasting states and fecal and urine samples were collected. Results Regardless of particle size of corn, the ATTD of gross energy (GE), N, and acid-hydrolyzed ether extract (AEE), and the concentration of NE were greater (P < 0.05) in pelleted diets than in meal diets. Regardless of diet form, the ATTD of GE, N, and AEE, and the concentration of NE were increased (linear; P < 0.05) by reducing the particle size of corn, but the increase was greater in meal diets than in pelleted diets (interaction; P < 0.05). Conclusions Both pelleting and reduction of corn particle size increased nutrient digestibility and NE, but increases were greater in meal diets than in pelleted diets.

Abstract Objective This study aimed to describe the social representations constructed by the educational community about educational psychology and the educational psychologist in the school context. Method We used a qualitative methodology with a hermeneutical approach, with a total of 34 participants (principals, teachers, psychologists, students, and parents) from eight private schools in the city of Ibagué, Colombia. Data were collected through focus groups and semistructured interviews. Results Thematic network analysis was used to analyze the data, resulting in three global themes that illustrate the main social representations. The results indicate that differentiation from clinical psychology and school counseling are points of reference for identifying educational psychology as an applied discipline and understanding the role of the educational psychologist in schools. Conclusion It is argued that representations and practices related to traditional roles are being transformed towards institutional and contextual practices.

Abstract Background Comprehensive data on patients at high risk of sudden cardiac death (SCD) in emerging countries are lacking. The aim was to deepen our understanding of the SCD phenotype and identify risk factors for death among patients at high risk of SCD in emerging countries. Methods Patients who met the class I indication for implantable cardioverter-defibrillator (ICD) implantation according to guideline recommendations in 17 countries and regions underrepresented in previous trials were enrolled. Countries were stratified by the WHO regional classification. Patients were or were not implanted with an ICD at their discretion. The outcomes were all-cause mortality and SCD. Results We enrolled 4222 patients, and 3889 patients were included in the analysis. The mean follow-up period was 21.6 ± 10.2 months. There were 433 (11.1%) instances of all-cause mortality and 117 (3.0%) cases of SCD. All-cause mortality was highest in primary prevention (PP) patients from Southeast Asia and secondary prevention (SP) patients from the Middle East and Africa. The SCD rates among PP and SP patients were both highest in South Asia. Multivariate Cox regression modelling demonstrated that in addition to the independent predictors identified in previous studies, both geographic region and ICD use were associated with all-cause mortality in patients with high SCD risk. Primary prophylactic ICD implantation was associated with a 36% (HR = 0.64, 95% CI 0.531–0.802, p

Chronic Obstructive Pulmonary Disease (COPD) is an inflammatory process of the lung inducing persistent airflow limitation. Extensive systemic effects, such as skeletal muscle dysfunction, often characterize these patients and severely limit life expectancy. Despite considerable research efforts, the molecular basis of muscle degeneration in COPD is still a matter of intense debate. In this study, we have applied a network biology approach to model the relationship between muscle molecular and physiological response to training and systemic inflammatory mediators. Our model shows that failure to co-ordinately activate expression of several tissue remodelling and bioenergetics pathways is a specific landmark of COPD diseased muscles. Our findings also suggest that this phenomenon may be linked to an abnormal expression of a number of histone modifiers, which we discovered correlate with oxygen utilization. These observations raised the interesting possibility that cell hypoxia may be a key factor driving skeletal muscle degeneration in COPD patients.

Summary: Perturbation of the apoptosis and necroptosis pathways critically influences embryogenesis. Receptor-associated protein kinase-1 (RIPK1) interacts with Fas-associated via death domain (FADD)-caspase-8-cellular Flice-like inhibitory protein long (cFLIPL) to regulate both extrinsic apoptosis and necroptosis. Here, we describe Ripk1-mutant animals (Ripk1R588E [RE]) in which the interaction between FADD and RIPK1 is disrupted, leading to embryonic lethality. This lethality is not prevented by further removal of the kinase activity of Ripk1 (Ripk1R588E K45A [REKA]). Both Ripk1RE and Ripk1REKA animals survive to adulthood upon ablation of Ripk3. While embryonic lethality of Ripk1RE mice is prevented by ablation of the necroptosis effector mixed lineage kinase-like (MLKL), animals succumb to inflammation after birth. In contrast, Mlkl ablation does not prevent the death of Ripk1REKA embryos, but animals reach adulthood when both MLKL and caspase-8 are removed. Ablation of the nucleic acid sensor Zbp1 largely prevents lethality in both Ripk1RE and Ripk1REKA embryos. Thus, the RIPK1-FADD interaction prevents Z-DNA binding protein-1 (ZBP1)-induced, RIPK3-caspase-8-mediated embryonic lethality, affected by the kinase activity of RIPK1.

The franciscana dolphin is a small, vulnerable species often caught in artisanal gillnets. This study aims to provide a comprehensive assessment of their acoustic capabilities by using advanced equipment to collect a large dataset of wideband, continuous recordings. We examined the detailed acoustic signals of franciscana dolphins, comparing the sounds from rehabilitated dolphins in captivity with those of wild dolphins near fishing nets. Significant differences in acoustic characteristics were found between neonates and older dolphins, with juvenile and wild dolphins showing similar features. For the first time, repetition patterns in click production were identified, highlighting the importance of understanding the context of these sounds in regards to feeding and communication. This study emphasizes the need for detecting neonates for species protection and suggests the potential for developing acoustic classifiers specific to different age groups. Our findings offer valuable insights for conservation efforts and the development of protection strategies for franciscana dolphins.

Abstract Background Uncertainty around the risk of COVID-19 to pregnant women and their babies prompted precautionary restrictions on their health and care during the pandemic. Maternity services had to adapt to changing Government guidance. Coupled with the imposition of national lockdowns in England and restrictions on daily activities, women’s experiences of pregnancy, childbirth and the postpartum period, and their access to services, changed rapidly. This study was designed to understand women’s experiences of pregnancy, labour and childbirth and caring for a baby during this time. Methods This was an inductive longitudinal qualitative study, using in-depth interviews by telephone with women in Bradford, UK, at three timepoints during their maternity journey (18 women at timepoint one, 13 at timepoint two and 14 at timepoint three). Key topics explored were physical and mental wellbeing, experience of healthcare services, relationships with partners and general impact of the pandemic. Data were analysed using the Framework approach. A longitudinal synthesis identified over-arching themes. Results Three longitudinal themes captured what was important to women: (1) women feared being alone at critical points in their maternity journey, (2) the pandemic created new norms for maternity services and women’s care, and (3) finding ways to navigate the COVID-19 pandemic in pregnancy and with a baby. Conclusions Modifications to maternity services impacted significantly on women’s experiences. The findings have informed national and local decisions about how best to direct resources to reduce the impact of COVID-19 restrictions and the longer-term psychological impact on women during pregnancy and postnatally.

El artículo describe las tendencias tecnológicas emergentes utilizadas por los actores ilegales del sistema de drogas ilícitas para dinamizar el narcotráfico; especialmente, la posibilidad del anonimato de la operación criminal, el recaudo y lavado de activos de la actividad ilegal y la entrega de las drogas ilegales a través del ciberespacio. Dicho análisis se construye a partir de la experiencia inicial con la construcción de la Unidad Investigativa en Cibernarcotráfico, adscrita a la Dirección de Antinarcóticos, y la revisión y sistematización del estado del arte de la comercialización de drogas en línea de los últimos cuatro años. En este proceso, y como herramientas del fenómeno criminal del cibernarcotráfico, se identifican tres ejes principales de análisis que se abordarán en este documento: redes sociales, cibercrimen y criptoactivos; todos ellos, elementos que, combinados y analizados con las tendencias que dinamizan el fenómeno y los actores de mayor influencia presentes, permiten proyectar tres escenarios probables a mediano plazo.

Summary: In several long-lived Caenorhabditis elegans strains, such as insulin/IGF-1 receptor daf-2 mutants, enhanced proteostatic mechanisms are accompanied by elevated intestinal lipid stores, but their role in longevity is unclear. Here, while determining the regulatory network of the selective autophagy receptor SQST-1/SQSTM1, we uncovered an important role for lipid droplets in proteostasis and longevity. Using genome-wide RNAi screening, we identified several SQST-1 modulators, including lipid droplets-associated and aggregation-prone proteins. Expansion of intestinal lipid droplets by silencing the conserved cytosolic triacylglycerol lipase gene atgl-1/ATGL enhanced autophagy, and extended lifespan. Notably, a substantial amount of ubiquitinated proteins were found on lipid droplets. Reducing lipid droplet levels exacerbated the proteostatic collapse when autophagy or proteasome function was compromised, and significantly reduced the lifespan of long-lived daf-2 animals. Altogether, our study uncovered a key role for lipid droplets in C. elegans as a proteostatic mediator that modulates ubiquitinated protein accumulation, facilitates autophagy, and promotes longevity.

Background & Objective: Despite the burden of sudden cardiac arrest (SCA) worldwide, implantable cardioverter-defibrillators (ICDs) are underutilized, particularly in Asia, Latin America, Eastern Europe, the Middle East, and Africa. The Improve SCA trial demonstrated that primary prevention (PP) patients in these regions benefit from an ICD or a cardiac resynchronization therapy defibrillator (CRT-D). We aimed to compare the rate of device therapy and mortality among ischemic and non-ischemic cardiomyopathy (ICM and NICM) PP patients who met guideline indications for ICD therapy and had an ICD/CRT-D implanted. Methods: Improve SCA was a prospective, non-randomized, non-blinded multicenter trial that enrolled patients from the above-mentioned regions. All-cause mortality and device therapy were examined by cardiomyopathy (ICM vs NICM) and implantation status. Cox proportional hazards methods were used, adjusting for factors affecting mortality risk. Results: Of 1848 PP NICM patients, 1007 (54.5%) received ICD/CRT-D, while 303 of 581 (52.1%) PP ICM patients received an ICD/CRT-D. The all-cause mortality rate at 3 years for NICM patients with and without an ICD/CRT-D was 13.1% and 18.3%, respectively (HR 0.51, 95% CI 0.38–0.68, p

This article explores the implementation process of a User Acceptance Study to evaluate the feasibility of conducting cultural domain analysis (CDA) online during the COVID-19 pandemic. We conducted 19 cultural domain analysis sessions involving three techniques: free listing, pile sorts, and rank ordering. A diverse set of participants were recruited to help assess requirements and needs that researching online involves. We found that conducting CDA online is a feasible research method that offers benefits such as generating large amounts of data, making participants feel comfortable joining sessions from a safe space, providing anonymity, reducing research costs such as time and travel, and eliciting large numbers of responses. We also identified several factors for consideration when implementing CDA online and provide recommendations for improvement, including the aesthetics of the digital software employed, user accessibility and digital literacy, participants’ environments, Internet connection, and online-specific ethical issues.

Estudios recientes han reportado efectos benéficos de la vitamina D tanto en la prevención, como en el tratamiento de la enfermedad por COVID-19. Esto se ha relacionado principalmente con sus mecanismos de acción dentro del sistema renina angiotensina (SRA), la respuesta inmunitaria y las regulaciones de las citocinas proinflamatorias, ejes de importancia en la fisiopatología de la COVID-19.

Introduction Antiretroviral treatment turned HIV infection into a chronic disease and improved quality of life for people living with HIV. Dual-drug combinations have been shown to be effective in suppressing viral replication and can potentially reduce long-term drug-associated toxicities. We aim to investigate patients’ perceptions and experiences on the safety, effectiveness, tolerability and unmet needs of the dual-drug combination dolutegravir/lamivudine in Brighton and Hove, UK. In addition, we will conduct a comparative analysis between patients on dolutegravir/lamivudine and patients on other dual-drug and three-drug combinations. Finally, the study aims to provide recommendations to improve doctor–patient communication, knowledge and understanding of the treatment plan, and additional care that ought to be considered in patient-centred, holistic care plans.Methods and analysis Our qualitative methodological framework is based on three main methods: cultural domain analysis, focus group discussions and in-depth interviews. Cultural domain analysis employs a range of techniques (free listing, pile sorts and rankings) to elicit terms from informants regarding specific cultural domains (ie, groups of items that are perceived to be of the same kind). This framework has been codesigned with a patient representative to ensure relevance, suitability and coproduction of knowledge. All methods have been tested to take place online, as an option, via Zoom, Skype or Microsoft Teams. Padlet, an application to create online boards, will be used during the cultural domain analysis session. Data collected will be analysed following the completion of each method embracing an iterative approach through applied thematic analysis.Ethics and dissemination Ethical approval was obtained from the Health Research Authority (Reference 21/NW/0070). Findings will be used to produce recommendations to improve doctor and patient communication by identifying patients’ fears, worries, misconceptions and general concerns of their drug regimen. Conclusions will be disseminated via journal articles, conference papers and discussions through public engagement events.Project registration number IRAS number: 286277. NCT04901728.

Peripheral arterial disease (PAD) is the main cause of mortality in the western population and requires surgical intervention with the use of vascular substitutes, such as autologous veins or Dacron or PTFE prostheses. When this is not possible, it progresses to limb amputation. For cases where there is no autologous vascular substitute, tissue engineering with the production of neovessels may be a promising option. Previous experimental studies have shown in vitro that rabbit vena cava can be decellularized and serve as a scaffold for receiving mesenchymal stem cells (MSC), with subsequent differentiation into endothelial cells. The current study aimed to evaluate the behavior of a 3D product structure based on decellularized rabbit inferior vena cava (IVC) scaffolds seeded with adipose-tissue-derived stem cells (ASCs) and implanted in rabbits dorsally subcutaneously. We evaluated the induction of the inflammatory response in the animal. We found that stem cells were positive in reducing the inflammatory response induced by the decellularized scaffolds.

In this paper, a methodology for optimal decision making for electrical systems is addressed. This methodology seeks to identify and to prioritize the replacement and maintenance of a power asset fleet optimizing the return of investment. It fulfills this objective by considering the risk index, the replacement and maintenance costs, and the company revenue. The risk index is estimated and predicted for each asset using both its condition records and by evaluating the consequence of its failure. The condition is quantified as the probability of failure of the asset, and the consequence is determined by the impact of the asset failure on the whole system. Failure probability is estimated using the health index as scoring of asset condition. The consequence is evaluated considering a failure impact on the objectives of reliability (energy not supplied -ENS), environment, legality, and finance using Monte Carlo simulations for an assumed period of planning. Finally, the methodology was implemented in an open-source library called PywerAPM for assessing optimal decisions, where the proposed mathematical optimization problem is solved. As a benchmark, the power transformer fleet of the New England IEEE 39 Bus System was used. Condition records were provided by a local utility to compute the health index of each transformer. Subsequently, a Monte Carlo contingency simulation was performed to estimate the energy not supplied for a period of analysis of 10 years. As a result, the fleet is ranked according to risk index, and the optimal replacement and maintenance are estimated for the entire fleet.