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Abstract Hyperactivity mediated by synaptotoxic β-amyloid (Aβ) oligomers is one of the earliest forms of neuronal dysfunction in Alzheimer’s disease. In the search for a preventive treatment strategy, we tested the effect of scavenging Aβ peptides before Aβ plaque formation. Using in vivo two-photon calcium imaging and SF-iGluSnFR-based glutamate imaging in hippocampal slices, we demonstrate that an Aβ binding anticalin protein (Aβ-anticalin) can suppress early neuronal hyperactivity and synaptic glutamate accumulation in the APP23xPS45 mouse model of β-amyloidosis. Our results suggest that the sole targeting of Aβ monomers is sufficient for the hyperactivity-suppressing effect of the Aβ-anticalin at early disease stages. Biochemical and neurophysiological analyses indicate that the Aβ-anticalin-dependent depletion of naturally secreted Aβ monomers interrupts their aggregation to neurotoxic oligomers and, thereby, reverses early neuronal and synaptic dysfunctions. Thus, our results suggest that Aβ monomer scavenging plays a key role in the repair of neuronal function at early stages of AD.

In this article we consider the following fractional semilinear elliptic equation \[(-\Delta)^su+|x|^2u =\omega u+|u|^{2\sigma}u \quad \text{ in } \mathbb{R}^N,\] where \(s\in (0,1)\), \(N\gt 2s\), \(\sigma\in (0,\frac{2s}{N-2s})\) and \(\omega\in (0, \lambda_1)\). By using variational methods we show the existence of a symmetric decreasing ground state solution of this equation. Moreover, we study some continuity and differentiability properties of the ground state level. Finally, we consider a bifurcation type result.

Reusing waste as raw materials to produce other materials can entail a decrease in production costs and in the abusive use of natural resources. Furthermore, it can even improve the properties of the end product or material. In this sense, a review of the most relevant literature published in recent decades shows that numerous solutions have been proposed or implemented, such as its use to produce construction materials, catalysts, pigments, pozzolana, refractory materials, glass-ceramic products, etc. Our research group has verified the viability of using different types of waste as secondary raw materials to obtain several types of ceramic, glassy and glassceramic materials, as well as frits. This article highlights several types of industrial waste that have both non-toxic (Li, Ca and Mn) and highly toxic (Cr VI) differentiating elements that can be used in sintering and vitrification industrial processes to immobilise them or render them inert. We studied the compositions and characterised the various materials obtained, conducting toxicity and leaching tests on waste/materials designed with high amounts of chromium. A suggestion for future lines of research has been proposed.

Land use plays a crucial role in the stock of soil organic carbon (SOC) and soil nitrogen (SN). The aim of this study was to assess and characterize the effects of various soil management practices on the physicochemical properties of soil in a Mediterranean region in southeastern Spain. Texture, soil moisture, bulk density, pH, electrical conductivity, equivalent CaCO3 (%), soil organic matter and carbon, and Kjeldahl nitrogen were determined for the surface topsoil (0–5 cm, 180 samples) under three types of land cover: cropland, grassland, and urban soil. The main soil textures were silt, silt loam, and sandy loam with low percentages of soil moisture in all soil samples and lower bulk density values in cropland and grassland areas. The pH was alkaline and the electrical conductivity as well as the equivalent calcium carbonate content were moderate to high. Organic matter estimated using the LOI and WB methods varied in the order cropland > grassland > urban soil. The results obtained for SOC and SN indicate that cropland presented the highest stocks, followed by grassland and urban soil. The values determined for the C/N ratio were close to 10 in cropland and grassland, indicating that organic matter readily undergoes decomposition at these sites. Our results emphasize the importance of evaluating the effects and identifying the impacts of different soil management techniques, and further research is needed to better understand the potential to improve soil organic carbon and nitrogen storage in semiarid regions.

Writing skills play a major part in communication, whether in a typing or in a handwriting scenario. Thus, a decrease or even loss of these skills can be a major setback. The system described herein aims to promote handwriting rehabilitation through haptic guidance and analysis of characters written using a haptic joystick. The first goal of this work is the creation of a system that encourages a user to write better through repetition, and thus have an impact on the proprioceptive system. In the second part of this work, there is a character analysis model evolution. Character analysis is performed by digit or letter classification and quantification of written characters quality. As such, different methods are studied and evaluated to achieve the best classification accuracy. Regarding handwritten characters classification, the pre-eminent procedure for digits consists in the use of Histogram of Oriented Gradients coupled with a multiclass Support Vector Machine (HOG-SVM) whereas for letters the strategy involves using a Convolutional Neural Network (CNN). For handwriting quality quantification, Dynamic Time Warping (DTW) was performed between the written character and a reference image of the same character. Finally, haptic guidance impact in a handwriting retraining in rehabilitation scenario is evaluated.

The Argentine shortfin squid Illex argentinus is one of the most important commercial species for the Argentine fisheries. The understanding of its stock structure is therefore necessary to ensure fishery sustainability and, given the relevance of squids in the regional food web, for biodiversity conservation. An overlap between parasitology and fisheries lies in the use of parasites as biological tags to identify the stock composition of exploited resources, however, the efficiency of this methodology has been questioned for stock assessment in cephalopods. In this work, the value of parasite assemblages of I. argentinus to discriminate between the co-occurring summer spawning stock (SSS) and south patagonic stock (SPS) in a mixing area over the Patagonian continental shelf during summer was evaluated for two cohorts. Five shortfin squid samples corresponding to SSS and SPS were examined for metazoan parasites. The squid size affected the parasite assemblage similarities, conversely, no gender effect on the infracommunities was observed. Multivariate analysis evidenced similarity in parasite assemblage composition and structure between both stocks captured in the mixing area on the same date. This similarity was related to the presence of short-lived trophically transmitted parasites, which are associated with their recently consumed food items and, indirectly, to the oceanographic conditions. The same set of host and environmental variables were identified as the most probable causes of the temporal variability observed in parasite assemblages between SPS cohorts and even intra-cohort. Despite the value of parasites as tags for discriminating squid stocks may have little value when cohabiting stocks are analysed, their variability could serve as a valuable indicator of environmental conditions. The use of parasites as biological tags to discriminate stocks needs to be verified at different spatiotemporal scales, including samples from other non-sympatric stocks in the analyses.

The Argentine shortfin squid, Illex argentinus, inhabits in the southwest Atlantic; it is a semelparous species which grows rapidly along its 1 year lifespan. The identification of its stocks is critical for sustainable fishery exploitation. Parasites have been used as biological indicators in a lower number of studies dealing with squids, therefore a validation of this methodology is necessary. The intra- and inter-cohort variability of parasite assemblages in the summer-spawning stock of I. argentinus was analysed to assess their value as indicators of stock structure. Four squid samples from the continental shelf of central Patagonia, corresponding to 3 consecutive cohorts, were examined for metazoan parasites. Results evidenced heterogeneity in terms of parasite assemblage composition and structure, dominated by short-lived gastrointestinal parasites, with a strong influence of host size, but no effect of squid sex. These changes are related to their recent habitats and diets, which change with ontogeny and migrations, clouding any interpretation of patterns when samples spatially or temporally separated are compared. Many squid species share these characteristics; therefore, it is recommended that the use of parasites as biological tags should be restricted to simultaneous sampling, while size or age must be considered for deriving proper conclusions.

Abstract Background CPX‐351 is approved for the treatment of therapy related acute myeloid leukemia (t‐AML) and AML with myelodysplastic related changes (MRC‐AML). The benefits of this treatment over standard chemotherapy has not been addressed in well matched cohorts of real‐life patients. Methods Retrospective analysis of AML patients treated with CPX‐351 as per routine practice. A propensity score matching (PSM) was used to compare their main outcomes with those observed in a matched cohort among 765 historical patients receiving intensive chemotherapy (IC), all of them reported to the PETHEMA epidemiologic registry. Results Median age of 79 patients treated with CPX‐351 was 67 years old (interquartile range 62–71), 53 were MRC‐AML. The complete remission (CR) rate or CR without recovery (CRi) after 1 or 2 cycles of CPX‐351 was 52%, 60‐days mortality 18%, measurable residual disease

This paper reflects on the importance of employability skills for higher education students in the present and future working environment to determine the impact these skills may have on student competitiveness and satisfaction. The study focused on university students in the Madrid region during their final academic year who participated in a teaching activity that launched real business challenges. We created a model that analyzed the impact of employability skills on student competitiveness and satisfaction and the mediating role of competitiveness in two different moments (before and during the COVID-19 pandemic). Empirical findings suggest that students' improved employability skills increased their competitiveness and satisfaction, with competitiveness as a mediating factor. Thus, academic authorities must focus on students acquiring employability skills, which are among the most valuable in the labour market and positively impact student competitiveness and satisfaction. This way, future graduates can work successfully in a changing and demanding world and find positions aligned with their training. In contrast to some studies that place the teacher as the research target, ours focused on the student and the impact these skills have on the variables mentioned.

BACKGROUND: The onset of the COVID-19 pandemic made changes to the Philippine medical education system to transfer to an online setting, which meant the loss of practical skills needed for future clinical encounters. Most students consider the desire to serve others as their motivation to pursue medicine, but stated that online learning was more favorable for theoretical lessons and not for practical skills. These students had to cope with lifestyle changes which challenged their resolve, as well as deal with the technology and infrastructure required for online learning. The study aimed to compare the strength and nature of motivations of medical students to pursue their studies before and after the onset of the pandemic, and to propose recommendations to support them through the pandemic and beyond. METHODS: Semi-structured interviews were conducted using a study questionnaire that dealt with determining respondents’ motivations for pursuing a medical degree, the impact of the pandemic and how it may have changed their motivations, and what recommendations they can propose to motivate other medical students. Interview transcripts were then analyzed through a qualitative inductive thematic analysis. Pre-clinical and clinical students (clerks and postgraduate interns) enrolled during SY 2020-2021 from Metro Manila and from among the 3 major Philippine island groups were selected to approximate the distribution of medical schools across the country. A total of 17 eligible participants were selected through purposive sampling of different personal backgrounds. Recruitment and call for participants were coursed through the Association of Philippine Medical Colleges - Student Network as well as through social media. Data from interview transcripts were familiarized and ideas from important recurring patterns shared among respondents’ answers were made into codes, which were subsequently organized into themes both unique and generalizable across student groups. RESULTS: Six major themes arose: 1) Contextualizing the pre-clinical and clinical experiences, 2) Challenges of online learning; 3) Desire for lived experience; 4) Tensions between personal contexts and online learning; 5) Grit driven by a desire to serve; 6) Resilience over adversity and sunk cost. Most pre-clinical students were motivated to pursue medicine by a desire to serve, while clinical students were straightforward about financial reward as motivation. Despite the limitations of online education, lack of social interaction and skills training, medical students had strengthened motivations to continue their studies as the pandemic highlighted the need for physicians, reinforcing their intrinsic desire to serve others. Mental health and financial issues were a concern for some, but these students did not wish to quit so as not to lose momentum with their studies. CONCLUSION: While most medical students interviewed felt more motivated in pursuing their studies during the pandemic, there was a desire and a call for more support in their studies and training. Their personal stories suggested there is room for improvement in certain aspects of local medical education. Addressing their concerns through financial and educational support, and bridging clinical skills with online learning would thus help them create quality healthcare in the pandemic context and beyond.

In this paper, the bandwidth dependence of the propagation channel for Body Area Networks (BANs) in circular metallic environments is addressed and models are proposed to evaluate the appropriate short-term fading margins that should be considered as a function of the system bandwidth. The deployment of BANs in metallic indoor environments, such as ships, factories, warehouses and other similar environments, involves additional challenges compared to other indoor environments due to the specific propagation effects in this type of environments (i.e., with strong reflections). No studies of this kind and for this type of environment can be found in literature, giving the motivation for this work. Bandwidth dependent values of delay spread are also presented and discussed. It is observed that for a system bandwidth up to 100 MHz the fading depth is composed of three main stages, with the transitions between these stages being associated with the system ability to discriminate arriving rays at the receiver. Average values of fading depth are 16.4, 13.2 and 11.0 dB for stages 1, 2 and 3, respectively, the difference between consecutive stages ranging between 2.2 to 3.2 dB. For a system bandwidth larger than 100 MHz, the fading depth decreases with an increasing system bandwidth, with an average decay rate close to 3 dB per 100 MHz bandwidth, being about 2 dB for system bandwidths above 400 MHz.

Abstract Background Patient-derived organoids (PDOs) from advanced colorectal cancer (CRC) patients could be a key platform to predict drug response and discover new biomarkers. We aimed to integrate PDO drug response with multi-omics characterization beyond genomics. Methods We generated 29 PDO lines from 22 advanced CRC patients and provided a morphologic, genomic, and transcriptomic characterization. We performed drug sensitivity assays with a panel of both standard and non-standard agents in five long-term cultures, and integrated drug response with a baseline proteomic and transcriptomic characterization by SWATH-MS and RNA-seq analysis, respectively. Results PDOs were successfully generated from heavily pre-treated patients, including a paired model of advanced MSI high CRC deriving from pre- and post-chemotherapy liver metastasis. Our PDOs faithfully reproduced genomic and phenotypic features of original tissue. Drug panel testing identified differential response among PDOs, particularly to oxaliplatin and palbociclib. Proteotranscriptomic analyses revealed that oxaliplatin non-responder PDOs present enrichment of the t-RNA aminoacylation process and showed a shift towards oxidative phosphorylation pathway dependence, while an exceptional response to palbociclib was detected in a PDO with activation of MYC and enrichment of chaperonin T-complex protein Ring Complex (TRiC), involved in proteome integrity. Proteotranscriptomic data fusion confirmed these results within a highly integrated network of functional processes involved in differential response to drugs. Conclusions Our strategy of integrating PDOs drug sensitivity with SWATH-mass spectrometry and RNA-seq allowed us to identify different baseline proteins and gene expression profiles with the potential to predict treatment response/resistance and to help in the development of effective and personalized cancer therapeutics.

The basolateral amygdala (BLA) contains interneurons that express neuropeptide Y (NPY) and vasoactive intestinal polypeptide (VIP), both of which are involved in the regulation of functions and behaviors that undergo deterioration with aging. There is considerable evidence that, in some brain areas, the expression of NPY and VIP might be modulated by acetylcholine. Importantly, the BLA is one of the brain regions that has one of the densest cholinergic innervations, which arise mainly from the basal forebrain cholinergic neurons. These cholinergic neurons depend on nerve growth factor (NGF) for their survival, connectivity, and function. Thus, in this study, we sought to determine if aging alters the densities of NPY- and VIP-positive neurons and cholinergic varicosities in the BLA and, in the affirmative, if those changes might rely on insufficient trophic support provided by NGF. The number of NPY-positive neurons was significantly reduced in aged rats, whereas the number of VIP-immunoreactive neurons was unaltered. The decreased NPY expression was fully reversed by the infusion of NGF in the lateral ventricle. The density of cholinergic varicosities was similar in adult and old rats. On the other hand, the density of cholinergic varicosities is significantly higher in old rats treated with NGF than in adult and old rats. Our results indicate a dissimilar resistance of different populations of BLA interneurons to aging. Furthermore, the present data also show that the BLA cholinergic innervation is particularly resistant to aging effects. Finally, our results also show that the reduced NPY expression in the BLA of aged rats can be related to changes in the NGF neurotrophic support.

A theoretical molecular simulation study of the encapsulation of gaseous SO2 at different temperature conditions in a type II porous liquid is presented here. The system is composed of cage cryptophane-111 molecules that are dispersed in dichloromethane, and it is described using an atomistic modelling of molecular dynamics. Gaseous SO2 tended to almost fully occupy cryptophane-111 cavities throughout the simulation. Calculations were performed at 300 K and 283 K, and some insights into the different adsorption found in each case were obtained. Simulations with different system sizes were also studied. An experimental-like approach was also employed by inserting a SO2 bubble in the simulation box. Finally, an evaluation of the radial distribution function of cryptophane-111 and gaseous SO2 was also performed. From the results obtained, the feasibility of a renewable separation and storage method for SO2 using porous liquids is mentioned.

Oxidative stress is characterized by an increase in reactive oxygen species or a decrease in antioxidants in the body. This imbalance leads to detrimental effects, including inflammation and multiple chronic diseases, ranging from impaired wound healing to highly impacting pathologies in the neural and cardiovascular systems, or the bone, amongst others. However, supplying compounds with antioxidant activity is hampered by their low bioavailability. The development of biomaterials with antioxidant capacity is poised to overcome this roadblock. Moreover, in the treatment of chronic inflammation, material-based strategies would allow the controlled and targeted release of antioxidants into the affected tissue. In this review, we revise the main causes and effects of oxidative stress, and survey antioxidant biomaterials used for the treatment of chronic wounds, neurodegenerative diseases, cardiovascular diseases (focusing on cardiac infarction, myocardial ischemia-reperfusion injury and atherosclerosis) and osteoporosis. We anticipate that these developments will lead to the emergence of new technologies for tissue engineering, control of oxidative stress and prevention of diseases associated with oxidative stress.

Transthyretin (TTR) amyloid cardiomyopathy (ATTR-CM) is a life-threatening disease caused by the abnormal production of misfolded TTR protein by liver cells, which is then released systemically. Its amyloid deposition in the heart is linked to cardiac toxicity and progression toward heart failure. A human induced pluripotent stem cell (iPSC) line was generated from peripheral blood mononuclear cells (PBMCs) from a patient suffering familial transthyretin amyloid cardiomyopathy carrying a c.128G>A (p.Ser43Asn) mutation in the TTR gene. This iPSC line offers a useful resource to study the disease pathophysiology and a cell-based model for therapeutic discovery.

Treatment options for patients with secondary acute myeloid leukemia (sAML) and AML with myeloid-related changes (AMLMRC) aged 60 to 75 years are scarce and unsuitable. A pivotal trial showed that CPX-351 improved complete remission with/without incomplete recovery (CR/CRi) and overall survival (OS) as compared with standard "3+7" regimens. We retrospectively analyze outcomes of 765 patients with sAML and AML-MRC aged 60 to 75 years treated with intensive chemotherapy, reported to the PETHEMA registry before CPX-351 became available. The CR/CRi rate was 48%, median OS was 7.6 months (95% confidence interval [CI]: 6.7-8.5) and event-free survival (EFS) 2.7 months (95% CI: 2-3.3), without differences between intensive chemotherapy regimens and AML type. Multivariate analyses identified age ≥70 years, Eastern Cooperative Oncology Group performance status ≥1 as independent adverse prognostic factors for CR/CRi and OS, while favorable/intermediate cytogenetic risk and NPM1 were favorable prognostic factors. Patients receiving allogeneic stem cell transplant (HSCT), autologous HSCT, and those who completed more consolidation cycles showed improved OS. This large study suggests that classical intensive chemotherapy could lead to similar CR/CRi rates with slightly shorter median OS than CPX-351.

Aunque la doctrina del TC sobre la cláusula de supletoriedad del derecho estatal del artículo 149.3 CE no está exenta de crítica, su orientación puede considerarse estable y aclarada desde las conocidas Sentencias 118/1996 y 61/1997, que se decantaron definitivamente por considerarla una norma ordenadora de la aplicación de las normas en el Estado compuesto configurado por la CE. No obstante, la STS, Sala de lo Contencioso-Administrativo, núm. 422/2022, que sirve de apoyo a este análisis, se separa de los criterios jurisprudenciales del TC y realiza una aplicación supletoria de la ley 19/2013, de 9 de diciembre, de transparencia, acceso a la información pública y buen gobierno, que es básica, integrando una presunta laguna de la Ley 12/2014, de 16 de diciembre, de Transparencia y Participación Ciudadana de la Comunidad Autónoma de la Región de Murcia. Esta aplicación supletoria de la ley básica produce, además, el efecto de modificar el régimen jurídico de la transparencia de las corporaciones locales de la Región de Murcia, que es parcialmente competencia autonómica, y modifica también el régimen del Consejo de la Transparencia de la Región de Murcia, materia que es de la exclusiva competencia autonómica sobre autoorganización.

The aim of this documentary review was to determine the level of scientific production on environmental analysis tools and certifications for sustainable cities and communities, or “Neighbourhood Sustainability Assessment Tools”, worldwide between the years 2016 and 2023, considering as a precedent the appearance of the SDG 2030 and SDG 11. The analysis developed in this work was carried out based on WoS, Scopus and ScienceDirect. The eligibility of the results of 685 potential articles, in addition to complementary articles, was evaluated, leading to 27 selected reviews. Our analysis revealed the main and most recent results post implementation of sustainability measures, identifying limitations, success factors, trends and forecasts for the future selection, development or improvement of evaluation tools for the sustainability of human sites and describing strategies specific to local realities, which are valid from a global point of view but include the particularities of distinct communities in specific places.

Abstract The COVID‐19 pandemic has resulted in another global health crisis with millions of individuals with Long Covid experiencing disability, worse health‐related quality of life, and productivity and income losses. Despite its impact on population health outcomes, health systems, and the economy, there remains a need for a global consensus on its standard definition, diagnostic approaches, and treatment plans to manage symptoms. In many low‐ and middle‐income countries (LMICs), there are limited published estimates on Long Covid, limited studies on its diagnostics and therapeutics, and limited media and news coverage. We advocate for a global action plan and necessary investments on Long Covid research and treatment, meaningful involvement of patients and cooperation between high‐income countries and LMICs, stronger and more effective public health communication surrounding the risks of Long Covid, and support toward financial risk protection as advocated by Universal Health Care.

Introduction: Evidence for the efficiency of highly-effective triple-CFTR-modulatory therapy with elexacaftor/tezacaftor/ivacaftor (ETI), either demonstrated in clinical trials or by in vitro testing, is lacking for about 10% of people with cystic fibrosis (pwCF) with rare mutations. Comprehensive assessment of CFTR function can provide critical information on the impact of ETI on CFTR function gains for such rare mutations, lending argument of the prescription of ETI. The mutation c.165-2A>G is a rare acceptor splice mutation that has not yet been functionally characterized. We here describe the functional changes induced by ETI in two brothers who are compound heterozygous for the splice mutations c.273+1G>C and c.165-2A>G.Methods: We assessed the effects of ETI on CFTR function by quantitative pilocarpine iontophoresis (QPIT), nasal potential difference measurements (nPD), intestinal current measurements (ICM), β-adrenergic sweat secretion tests (SST) and multiple breath washout (MBW) prior to and 4 months after the initiation of ETI.Results: Functional CFTR analysis prior to ETI showed no CFTR function in the respiratory and intestinal epithelia and in the sweat gland reabsorptive duct in either brother. In contrast, β-adrenergic stimulated, CFTR-mediated sweat secretion was detectable in the CF range. Under ETI, both brothers continued to exhibit high sweat chloride concentration in QPIT, evidence of low residual CFTR function in the respiratory epithelia, but normalized β-adrenergically stimulated production of primary sweat.Discussion: Our results are the first to demonstrate that the c.165-2A>G/c.273+1G>C mutation genotype permits mutant CFTR protein expression. We showed organ-specific differences in the expression of CFTR and consecutive responses to ETI of the c.165-2A>G/c.273+1G>C CFTR mutants that are probably accomplished by non-canonical CFTR mRNA isoforms. This showcase tells us that the individual response of rare CFTR mutations to highly-effective CFTR modulation cannot be predicted from assays in standard cell cultures, but requires the personalized multi-organ assessment by CFTR biomarkers.

This article shows an analysis of the energy demand in Peru and the impact of hydrocarbons on the Peruvian energy matrix and its future projection. The essay is based on a review of the current context, the components and uses of the energy matrix, as well as the design of scenarios to identify the trend of demand in the coming years. This document would serve as a basis for proposing the conditions under which the hydrocarbon industry in Peru should develop with a long-term vision.

Abstract The research on porous materials for the selective capture of fluorinated gases (F‐gases) is key to reduce their emissions. Here, the adsorption of difluoromethane (R‐32), pentafluoroethane (R‐125), and 1,1,1,2‐tetrafluoroethane (R‐134a) is studied in four metal–organic frameworks (MOFs: Cu‐benzene‐1,3,5‐tricarboxylate, zeolitic imidazolate framework‐8, MOF‐177, and MIL‐53(Al)) and in one zeolite (ZSM‐5) with the aim to develop technologies for the efficient capture and separation of high global warming potential blends containing these gases. Single‐component sorption equilibria of the pure gases are measured at three temperatures (283.15, 303.15, and 323.15 K) by gravimetry and correlated using the Tóth and Virial adsorption models, and selectivities toward R‐410A and R‐407F are determined by ideal adsorption solution theory. While at lower pressures, R‐125 and R‐134a are preferentially adsorbed in all materials, at higher pressures there is no selectivity, or it is shifted toward the adsorption R‐32. Furthermore, at high pressures, MOF‐177 shows the highest adsorption capacity for the three F‐gases. The results presented here show that the utilization of MOFs, as tailored made materials, is promising for the development of new approaches for the selective capture of F‐gases and for the separation of blends of these gases, which are used in commercial refrigeration.

In this paper, the influence of user mobility and on-body antenna placement on system loss in body-to-body communications in indoor and outdoor environments and different mobility scenarios is studied, based on system loss measurements at 2.45 GHz. The novelty of this work lies on the proposal of a classification model to characterise the effect of user mobility and path visibility on system loss, allowing to identify the best set of on-body antenna placements. To quantify the influence of visibility and mobility on the average system loss, a combined score is proposed, allowing to map system loss onto the degree of visibility and mobility that depends on the scenario being considered and on on-body antenna placements. Overall, a good agreement is observed between the proposed classification model and the average measured values of system loss, with the higher values of combined scores being associated with lower values of systems loss. For the cases under study, the average values of system loss are 61.6 dB for the cases of the antennas being positioned only on the front of the body and/or the head, and 64.5 dB if at least one of the antennas is placed on an arm.

There is a need for investigating radio channels for Body Area Networks considering the depolarisation phenomenon and new types of environments, since these aspects are becoming very important for systems design and deployment. This paper presents an analysis of cross-polarisation discrimination for off-body channels based on a measurement campaign performed in a passenger ferryboat, i.e., where all walls, floors and ceilings are made of metal. Firstly, the measurement campaign, including test-bench and scenarios, as well as the analysis approach, including classification of mutual antennas’ orientation and definition of parameters are described. The analysis of results includes distance, on-body antennas location and several scenarios, addressing statistical parameters. Mean values for the cross-polarisation discrimination are in the range of [3.7, 6.8] dB while the standard deviation is around 10.0 dB. There is no dependence of the cross-polarisation discrimination on distance, within the measured range (up to 16 m). It is found that there is no correlation between radio signals received by vertically and horizontally polarised receiving antennas, hence, enabling the application of polarisation diversity in Body Area Networks. The Normal Distribution is the best fit for describing cross-polarisation discrimination, as shown by the analysis of goodness of fit parameters, since it passes many of the tests.

Background SARS-CoV-2 is continuously disseminating worldwide. The development of strategies to break transmission is mandatory. Aim of the study To investigate the potential of cetylpyridinium chloride (CPC) as a viral inhibitor. Methods SARS-CoV-2 Virus Like-Particles (VLPs) were incubated with CPC, a potent surfactant routinely included in mouthwash preparations. Results Concentrations of 0.05% CPC (w/v) commonly used in mouthwash preparations are sufficient to promote the rupture of SARS-CoV-2 VLP membranes. Conclusion Including CPC in mouthwashes could be a prophylactic strategy to keep SARS-CoV-2 from spreading.

Since the mid-20th century, the study of Self-Regulated Learning (SRL) has aimed to identify the distinctive characteristics that enable individuals to acquire new knowledge and skills under their control. The theory of Internal Self-Regulation vs. External-Regulation in Learning (SRL vs. ERL; 2017) has postulated that a large number of self-regulatory variables are mediated by regulated/non-regulated or dysregulated features of the context. After signing their informed consent, a total of 616 university students completed validated instruments of SRL vs. ERL, behavioral regulation (SRB), regulatory teaching (RT), and metacognitive study control strategies (SRS). Using an ex-post facto design and correlation, regression, structural equation model and mediation analyses, the present research aimed to establish multicausal predictive relationships among the analyzed variables. Results indicated positive predictive effects between the external regulation variables on the self-regulation variables in learning [regulation (SRL)/non-regulation (NRL)/dysregulation (DRL)]; as well as positive predictive effects between SRL on SRB, RT and metacognitive SRS. Additionally, external regulation (ERL) not only predicted but mediated numerous relations among the variables studied. Other findings and important considerations for future research in the field of self-regulation are discussed.

Naphthoquinones are a valuable source of secondary metabolites that are well known for their dye properties since ancient times. A wide range of biological activities have been described highlighting their cytotoxic activity, gaining the attention of researchers in recent years. In addition, it is also worth mentioning that many anticancer drugs possess a naphthoquinone backbone in their structure. Considering this background, the work described herein reports the evaluation of the cytotoxicity of different acyl and alkyl derivatives from juglone and lawsone that showed the best activity results from a etiolated wheat coleoptile bioassay. This bioassay is rapid, highly sensitive to a wide spectrum of activities, and is a powerful tool for detecting biologically active natural products. A preliminary cell viability bioassay was performed on cervix carcinoma (HeLa) cells for 24 h. The most promising compounds were further tested for apoptosis on different tumoral (IGROV-1 and SK-MEL-28) and non-tumoral (HEK-293) cell lines by flow cytometry. Results reveal that derivatives from lawsone (particularly derivative 4) were more cytotoxic on tumoral than in non-tumoral cells, showing similar results to those obtained with of etoposide, which is used as a positive control for apoptotic cell death. These findings encourage further studies on the development of new anticancer drugs for more directed therapies and reduced side effects with naphthoquinone skeleton.

Solar activity has been subject to increasingly more research in the last decades. Its influence on life on Earth is now better understood. Solar winds impact the earth’s magnetic field and atmosphere. They can disrupt satellite communication and navigation tools and even electrical power grids and several other infrastructure crucial for our technology-based society. Coronal mass ejections (CMEs), solar energetic particles, and flares are the main causes of problems that affect the systems mentioned. It is possible to predict some of those by monitoring the sun and analyzing the images obtained in different spectra, thus identifying solar phenomena related to its activity, such as filaments, pores, and sunspots. Several studies have already been carried out on the subject of automation of the mentioned analysis, most of which use neural networks and other machine learning approaches. In this work, we develop a method for sunspot detection based on the YOLOv5 network, applying it to a dataset of images from the Geophysical and Astronomical Observatory of the University of Coimbra (OGAUC), which has one of the oldest and more complete datasets of sun images in the world. Our method reaches mAP@.5 over 90% with YOLOv5s, which is higher than other methods previously applied for the same dataset. This shows that CNN models can be used in spectroheliographs for detecting and tracking sunspots.

Umbrella Sampling Molecular Dynamics has been used to determine transition energies for different guest molecules through hydroquinone β-clathrate nanochannels, as well as their temperature trend. This clathrate has been shown to successfully enclathrate different types of small gases with remarkable selectivity, and thus it has been proposed as a potential gas separation and storage medium. Most of these potential guest gases can be successfully modeled as single Lennard–Jones spheres. Then, to obtain a general view of diffusion probabilities for different potential guest molecules, a comparative study for different virtual guest molecules described by different Lennard–Jones parameters has been performed. A regular temperature trend has been obtained for the transition energies for the molecular model characteristic parameter range explored. Finally, to locate the transition energy values of real gases within the space of phases explored, calculations have been repeated for molecular models of different noble gases and H2. The correlation results presented allow a wide interpolation ability for determining the transition energies of potential guest molecules stored or diffusing through the nanochannels of the studied clathrate structure.

The continuous growth of Internet data traffic is pushing the current radio-frequency wireless technologies up to their physical limits. To overcome the upcoming bandwidth bottleneck, Free-Space Optics (FSO) is currently deemed as a key breakthrough toward next-generation ultra-high-capacity wireless links. Despite its numerous advantages, FSO also entails several particular challenges regarding the mitigation of the stochastic impairments induced by turbulence and the strict alignment requirements. One of the main issues of FSO communication systems is the mitigation of pointing errors and angle-of-arrival (AoA) fluctuations, which arise from misalignments induced by atmospheric turbulence and vibrations at the transmitting and receiving stations. A common approach to mitigate the impact of pointing errors is the use of an acquisition, tracking and pointing (ATP) system on one or both ends of the FSO link. In this paper, we present a characterization of the pointing errors and the AoA impact on the power budget of the FSO link to quantify the misalignment impairments. Afterwards, we experimentally demonstrate an FSO link with an ATP mechanism at both ends, managed by a control plane that enables the continuous and accurate alignment of the FSO link. To increase the misalignment tolerance, the ATP mechanism comprises two stages: the first one is based on a spatial diversity method provided by a quadrant detector, while the second stage maximizes the optical received power. Lastly, the impact of the beam misalignment on the achievable information rate of a coherent optical wireless system is theoretically addressed and characterized.

A construção de barragens em Cabo Verde é um fato recente, sendo a primeira barragem construída em 2006, ainda na ausência de uma legislação sobre segurança de barragens. A falta de experiência no projeto de barragens pela engenharia nacional obrigou o governo a contratar empresas de consultoria internacionais para sua elaboração. A contratação em lotes ensejou que os projetos fossem elaborados de forma similar em metodologia de cálculo, de parâmetros de projeto e desenho. Nos projetos analisados, chamou atenção ao fato de se adotar a média dentre cinco fórmulas empíricas de cálculo do tempo de concentração (tc) em vez de se adotar o menor dos tempos para o dimensionamento hidrológico, que foi sempre dado pela fórmula de Kirpich, uma das mais empregadas na elaboração de tais estudos. Este trabalho investigou o risco hidrológico decorrente do uso do tempo de concentração médio avaliando a folga resultante no vertedouro para uma cheia milenar, concluindo pela insegurança dos projetos.

Sarah Patel,1,2 Bethany Doerfler,3 Katerine Boutros,4 Samson Ng,4 Machelle Manuel,5 Elayne DeSimone6 1Department of Gastroenterology and Hepatology, Weill Cornell Medicine, New York, NY, USA; 2Rutgers University, Piscataway, NJ, USA; 3Division of Gastroenterology, Northwestern Medicine, Chicago, IL, USA; 4Global Medical Affairs Gastroenterology & Hepatology, AbbVie Inc, Madison, NJ, USA; 5Ironwood Pharmaceuticals, Inc, Cambridge, MA, USA; 6Community Volunteers in Medicine, West Chester, PA, USACorrespondence: Sarah PatelDepartment of Gastroenterology and Hepatology, Weill Cornell Medicine, New York, NY, USATel +1-(908)-642-6979Email soneil86@gmail.comAbstract: Irritable bowel syndrome with constipation (IBS-C) and chronic idiopathic constipation (CIC) are two common disorders of gut–brain interaction. Affected patients often first present to their primary care providers seeking care for symptoms of constipation, abdominal pain, and bloating, which have a significant impact on their health-related quality of life. These patients often require extensive counseling and reassurance, and knowledge of reliable diagnostic criteria and treatment options is imperative to managing their conditions. Family medicine practitioners, including nurse practitioners and physician assistants, are uniquely qualified to provide a diagnosis and safe, effective management of these disorders. This article reviews the latest evidence and provides practical advice related to diagnosis and management of IBS-C and CIC.Keywords: advanced practice providers, chronic idiopathic constipation, constipation, irritable bowel syndrome, nurse practitioners, physician assistants

Due to the nature of health data, its sharing and reuse for research are limited by ethical, legal and technical barriers. The FAIR4Health project facilitated and promoted the application of FAIR principles in health research data, derived from the publicly funded health research initiatives to make them Findable, Accessible, Interoperable, and Reusable (FAIR). To confirm the feasibility of the FAIR4Health solution, we performed two pathfinder case studies to carry out federated machine learning algorithms on FAIRified datasets from five health research organizations. The case studies demonstrated the potential impact of the developed FAIR4Health solution on health outcomes and social care research. Finally, we promoted the FAIRified data to share and reuse in the European Union Health Research community, defining an effective EU-wide strategy for the use of FAIR principles in health research and preparing the ground for a roadmap for health research institutions. This scientific report presents a general overview of the FAIR4Health solution: from the FAIRification workflow design to translate raw data/metadata to FAIR data/metadata in the health research domain to the FAIR4Health demonstrators’ performance.

Background: Recent research on boredom suggests that it can emerge in situations characterized by over- and under-challenge. In learning contexts, this implies that high boredom may be experienced both by low- and high-achieving students. Aims: This research aimed to explore the existence and prevalence of boredom due to being over- and under-challenged in mathematics, for which empirical evidence is lacking. Sample: We employed a sample of 1.407 students (fifth to ninth graders) from all three secondary school tracks (lower, middle and upper) in Bavaria (Germany). Methods: Boredom was assessed via self-report and achievement via a standardized mathematics test. We used latent profile analysis to identify groups characterized by different levels of boredom and achievement, and we additionally examined gender and school track as group membership predictors. Results: Results revealed four distinct groups, of which two showed considerably high boredom. One was coupled with low achievement on the test (i.e. 'over-challenged group', 13% of the total sample), and one was coupled with high achievement (i.e. 'under-challenged group', 21%). Furthermore, we found a low boredom and high achievement (i.e. 'well-off group', 27%) and a relatively low boredom low achievement group (i.e. 'indifferent group', 39%). Girls were overrepresented in the over-challenged group, and students from the upper school track were underrepresented in the under-challenged group. Conclusion: Our research emphasizes the need to openly discuss and further investigate boredom due to being over- and under-challenged.

In this paper, the wideband characterization of the propagation channel in circular metallic indoor environments is addressed, regarding Body Area Networks and 5G small cells, an analytical model for the dependence of the mean delay and the average delay spread on the circle radius, the working frequency and the distance between the transmitter and the receiver being proposed. The derivation of the model is initially done analytically, based on optical physics, after which simulation results allow to obtain the values of the coefficients. The simulator was previously assessed with measurements at 2.45 GHz in a passenger ferry room with a circular shape. For a random positioning of the transmitter and the receiver, and a given distance between them, it is observed that the mean delay and the delay spread increase linearly with the radius; furthermore, the mean delay increases quadratically with the distance, while the delay spread has a concave parabolic behavior, with the maximum being at a distance equal to the radius. In a practical case, regarding the positioning of an Access Point inside the room, it is recommended that it is done at the circle center, in order to reduce delay spread.

Spagnolli, Massignan, Astolfi et al. design a new drug discovery approach, termed Pharmacological Protein Inactivation by Folding Intermediate Targeting, in which folding intermediates of disease-causing proteins are targeted. They test it on the cellular prion protein, identifying ligands stabilizing a folding intermediate and consequently promoting its degradation by the cellular quality control machinery.

In this study we analyse from a theoretical perspective the encapsulation of both gaseous H2 and CO2 at different conditions of pressure and temperature in a Type II porous liquid, composed by nanometric scale cryptophane-111 molecules dispersed in dichloromethane, using atomistic molecular dynamics. Gaseous H2 tends to occupy cryptophane–111’s cavities in the early stages of the simulation; however, a remarkably greater selectivity of CO2 adsorption can be seen in the course of the simulation. Calculations were performed at ambient conditions first, and then varying temperature and pressure, obtaining some insight about the different adsorption found in each case. An evaluation of the host molecule cavities accessible volume was also performed, based on the guest that occupies the pore. Finally, a discussion between the different intermolecular host–guest interactions is presented, justifying the different selectivity obtained in the molecular simulation calculations. From the results obtained, the feasibility of a renewable separation and storage method for CO2 using these nanometric scale porous liquids is pointed out.

Effective and safe COVID-19 vaccines have been developed at a rapid and unprecedented pace to control the spread of the virus, and prevent hospitalisations and deaths. However, COVID-19 vaccine uptake is challenged by vaccine hesitancy and anti-vaccination sentiments, a global shortage of vaccine supply, and inequitable vaccine distribution especially among low- and middle-income countries including the Philippines. In this paper, we explored vaccination narratives and challenges experienced and observed by Filipinos during the early vaccination period. We interviewed 35 individuals from a subsample of 1,599 survey respondents 18 years and older in the Philippines. The interviews were conducted in Filipino, Cebuano, and/or English via online platforms such as Zoom or via phone call. All interviews were recorded, transcribed verbatim, translated, and analysed using inductive content analysis. To highlight the complex reasons for delaying and/or refusing COVID-19 vaccines, we embedded our findings within the social ecological model. Our analysis showed that individual perceptions play a major role in the decision to vaccinate. Such perceptions are shaped by exposure to (mis)information amplified by the media, the community, and the health system. Social networks may either positively or negatively impact vaccination uptake, depending on their views on vaccines. Political issues contribute to vaccine brand hesitancy, resulting in vaccination delays and refusals. Perceptions about the inefficiency and inflexibility of the system also create additional barriers to the vaccine rollout in the country, especially among vulnerable and marginalised groups. Recognising and addressing concerns at all levels are needed to improve COVID-19 vaccination uptake and reach. Strengthening health literacy is a critical tool to combat misinformation that undermines vaccine confidence. Vaccination systems must also consider the needs of marginalised and vulnerable groups to ensure their access to vaccines. In all these efforts to improve vaccine uptake, governments will need to engage with communities to 'co-create' solutions.

With the increasing development of 5G and Body Area Network based systems being implemented in unusual environments, propagation inside metallic structures is a key aspect to characterize propagation effects inside ships and other similar environments, mostly composed of metallic walls. In this paper, indoor propagation inside circular metallic structures is addressed and fast fading statistical distributions parameters are obtained from simulation, being assessed with measurements at 2.45 GHz in a passenger ferry discotheque with an 8 m diameter circular shape. It is observed that, in this kind of environments, second order reflections are particularly relevant due to the walls' high reflective nature. Globally, it is concluded that the Rayleigh distribution can be used to characterize fast fading effects with no significant loss of accuracy compared to the Rice one, since a low value of the Rice parameter is observed, being below 3.1 dB, even under Line-of-Sight conditions. Moreover, it is observed that, from the fast fading viewpoint, the best transmitter position is at the circle center.

Introduction One of the known risk factors for fall incidents is the use of specific medications, fall-risk-increasing drugs (FRIDs). However, to date, there is uncertainty related to the effectiveness of deprescribing as a single intervention in falls prevention. Thus, a comprehensive update of the literature focusing on all settings in which older people receive healthcare and all deprescribing interventions is warranted to enhance the current knowledge.Methods and analysis This systematic review protocol follows the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A systematic search was performed in Cochrane Central Register of Controlled Trials, MEDLINE, Embase and PsycINFO (2 November 2020). We will also search in trial registers. We will include randomised controlled trials, in which any deprescribing intervention is compared with usual care and reports falls as an outcome. Both title and abstract screening and full-text screening will be done by two reviewers. The Cochrane Collaboration revised tool of Risk of Bias will be applied to perform risk of bias assessment. We will categorise the results separately for every setting. If a group of sufficiently comparable studies will be identified, we will perform a meta-analysis applying random effects model. We will investigate heterogeneity using a combination of visual inspection of the forest plot along with consideration of the χ2 test and the I2 statistic results. We have prespecified several subgroup and sensitivity analyses.Ethics and dissemination Ethics approval is not applicable for this study since no original data will be collected. The results will be disseminated through peer-reviewed publication and conference presentations. Furthermore, this systematic review will inform the recommendations of working group of polypharmacy and FRIDs of the anticipated World’s Falls Guidelines.PROSPERO registration number CRD42020218231.

The article questions the widespread idea that in the Constitutional Monarchy governments always won elections, finding that this was only happens with large party governments. Parties were therefore relevant in electoral acts, as well as bipartisanship was influenced by the electoral system. Public opinion was also relevant, resulting in government defeats in big cities. Between 1852 and 1890, consensus reforms prevailed to broaden voter participation, while after 1890 dictatorial reforms increase the pressure of governments on voters regarding the growing republican implantation.

Fire is a natural process with recognized recurrence. However, ongoing climate change and human activities are causing some disturbances in their natural regimes in most ecosystems. It is important to improve the methodologies used to evaluate the fire-induced changes in soils. This study aims at investigating the potential of the X-ray diffraction (XRD) technique to be used as a fingerprinting technique for burned soils. Multivariate analysis was employed to analyze the XRD data. Hierarchical Cluster Analysis (HCA) and local Partial Least Squares (PLS-2) models were performed. The soil samples are classified as Ferralsols and were collected from an Amazon region, Brazil, from forests, pastures and a slash-and-burn area. The studied temperatures ranged between 25 and 800 °C. Major differences were found for gibbsite, goethite and kaolinite contents due to dehydration. PLS-2 analysis presented better results than HCA as it provided information concerning the two features of the investigated soils, the collection site and the temperature. Therefore, it was possible to characterize soils from different sites and soils heated at different temperatures by using XRD data with multivariate analysis. Such methodology provided important information that may be used in areas with these environmental and soil conditions.

The repurposing of the CRISPR/Cas bacterial defense system against bacteriophages as simple and flexible molecular tools has revolutionized the field of gene editing. These tools are now widely used in basic research and clinical trials involving human somatic cells. However, a global moratorium on all clinical uses of human germline editing has been proposed because the technology still lacks the required efficacy and safety. Here we focus on the approaches developed since 2013 to decrease the frequency of unwanted mutations (the off-targets) during CRISPR-based gene editing.

Gelatin is a popular biopolymer for biomedical applications due to its harmless impact with a negligible inflammatory response in the host organism. Gelatin interacts with soluble molecules in aqueous media as ionic counterparts such as ionic liquids (ILs) to be used as cosolvents to generate the so-called Ionogels. The perfluorinated IL (FIL), 1-ethyl-3-methylpyridinium perfluorobutanesulfonate, has been selected as co-hydrosolvent for fish gelatin due to its low cytotoxicity and hydrophobicity aprotic polar structure to improve the drug aqueous solubility. A series of FIL/water emulsions with different FIL content and their corresponding shark gelatin/FIL Ionogel has been designed to enhance the drug solubility whilst retaining the mechanical structure and their nanostructure was probed by simultaneous SAXS/WAXS, FTIR and Raman spectroscopy, DSC and rheological experiments. Likewise, the FIL assisted the solubility of the antitumoural Doxorubicin whilst retaining the performing mechanical properties of the drug delivery system network for the drug storage as well as the local administration by a syringe. In addition, the different controlled release mechanisms of two different antitumoral such as Doxorubicin and Mithramycin from two different Ionogels formulations were compared to previous gelatin hydrogels which proved the key structure correlation required to attain specific therapeutic dosages.

La presente investigación, tiene por objeto analizar la contribución de la minería en términos de canon y otras regalías, así como la efectividad de la distribución y ejecución de estos recursos. En este estudio se observó, midió y analizó los índices de recaudación en términos monetarios; se determinó las características de los datos, a través de la recolección de los mismos; se utilizó el método inductivo-deductivo de forma específica a general. La revisión documental, se basó en la examinación de las transferencias económicas a las distintas regiones por canon minero y regalías, y el análisis de datos oficiales de páginas de transparencia de diversos entes ejecutores. Como conclusión se determina que el régimen tributario minero presenta ciertas debilidades, debido a la existencia de minería informal que no aporta canon ni regalías, la repartición inequitativa de presupuesto, y finalmente la ineficaz ejecución de los proyectos de inversión financiados con estos recursos, que no cumplen la finalidad pública que es la disminución de la pobreza, principalmente.

The continental collision process has made a large contribution to continental growth and reconfiguration of cratons throughout Earth history. Many of the mountain belts present today are the product of continental collision such as the Appalachians, the Alps, the Cordillera, the Himalaya, the Zagros, and the Papuan Fold and Thrust Belt. Though collisional mountain belts are generally elongate and laterally continuous, close inspection reveals disruptions and variations in thrust geometry and kinematics along the strike of the range. These lateral variations typically coincide with cross structures and have been documented in thrust fault systems with a variety of geometries and kinematic interpretations. In the Himalaya, cross faults provide segment boundaries that, in some cases separate zones of differing thrust geometry and may even localize microseismicity or limit areas of active seismicity on adjacent thrust systems. By compiling data on structural segmentation along the length of the Himalayan range, we find lateral variations at all levels within the Himalaya. Along the Gish fault of the eastern Indian Himalaya, there is evidence in the foreland for changes in thrust-belt geometry across the fault. The Gish, the Ganga, and the Yamuna faults all mark boundaries of salients and recesses at the mountain front. The Benkar fault in the Greater Himalayan sequence of eastern Nepal exhibits a brittle-ductile style of deformation with fabric that crosscuts the older thrust-sense foliation. Microseismicity data from several regions in Nepal shows linear, northeast-striking clusters of epicenters sub-parallel to cross faults. The map pattern of aftershock data from the 2015 Nepal earthquakes has an abrupt northeast-trending termination on its eastern side suggesting the presence of a structure of that orientation that limited slip. The orientations of the recognized cross faults and seismic patterns also align with the extensional zones to the north on the Tibetan Plateau and the Indian basement structures to the south. Results from multiple studies are consistent with a link between cross faults and either of these structural trends to the north or south and suggest that cross faults may play a role in segmenting deformation style and seismic activity along the length of the Himalaya.