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Computer-based interventions that aim to help students endorse a growth mindset have been designed and tested in high-income countries for a number of years. However, there is no evidence of their effectiveness in middle-income nations. In those studies, students' growth mindset has traditionally been measured using surveys where students report the extent to which they believe intelligence is fixed or malleable, without linking intelligence with a more specific dimension, such as math or language. In addition, these measurements have been undertaken without distinctions being made between personal ability ("my" intelligence) and more general abilities (everyone's intelligence). Therefore, by means of a randomized experiment, this study assesses the impact of a single-session online growth-mindset intervention in Chile on distinct measurements of the growth mindset of students (general, personal, and subject-specific), as well as their propensity to seek out challenges. Accordingly, a sample of 248 students was recruited from 9 and 11th grades in three secondary schools, all of whom were randomly assigned to either a treatment or control group. The intervention was found to increase their propensity to seek out challenges and to experience an increase in growth mindset scores in all tested dimensions. No evidence of the heterogeneity of results by gender or prior growth mindset was identified.

Technical innovation in neuroscience introduced powerful tools for measuring and manipulating neuronal activity via optical, chemogenetic, and calcium-imaging tools. These tools were initially tested primarily in male animals but are now increasingly being used in females as well. In this review, we consider how these tools may work differently in males and females. For example, we review sex differences in the metabolism of chemogenetic ligands and their downstream signaling effects. Optical tools more directly alter depolarization or hyperpolarization of neurons, but biological sex and gonadal hormones modulate synaptic inputs and intrinsic excitability. We review studies demonstrating that optogenetic manipulations are sometimes consistent across the rodent estrous cycle but within certain circuits; manipulations can vary across the ovarian cycle. Finally, calcium-imaging methods utilize genetically encoded calcium indicators to measure neuronal activity. Testosterone and estradiol can directly modulate calcium influx, and we consider these implications for interpreting the results of calcium-imaging studies. Together, our findings suggest that these neuroscientific tools may sometimes work differently in males and females and that users should be aware of these differences when applying these methods.

Fake news and artificial intelligence are phenomena addressed in academia and research within the fields of communication and audiovisual education. As a medium and language, cinema has mirrored these challenges, exemplified by the short film Deep Soria. The primary objective proposed in this study is to ascertain whether this short film, directed by Pedro Estepa in 2021, is perceived as a mockumentary and to explore students’ perceptions of the social issues it raises and the way it expresses them. An ad hoc questionnaire was employed specifically for the short film, enabling the assessment of 118 students from the Journalism and Primary Education Degree programmes at the University of Valladolid. The method used is exploratory and descriptive. Results were obtained by combining descriptive statistical analysis and content analysis of the open-ended questions in the questionnaire. Notably, the study highlights the detection of the documentary’s central themes- fake news and depopulation- the use of humour, the focus on depopulation, and suggestions for incorporating more elements of “everyday reality”, such as images and testimonies from the inhabitants of Soria and the city/province. At the same time, the short film has been reevaluated for its propensity to address social issues.

Abstract A key feature of cancer is the disruption of cell cycle regulation, which is characterized by the selective and abnormal activation of cyclin-dependent kinases (CDKs). Consequently, targeting CDKs via meriolins represents an attractive therapeutic approach for cancer therapy. Meriolins represent a semisynthetic compound class derived from meridianins and variolins with a known CDK inhibitory potential. Here, we analyzed the two novel derivatives meriolin 16 and meriolin 36 in comparison to other potent CDK inhibitors and could show that they displayed a high cytotoxic potential in different lymphoma and leukemia cell lines as well as in primary patient-derived lymphoma and leukemia cells. In a kinome screen, we showed that meriolin 16 and 36 prevalently inhibited most of the CDKs (such as CDK1, 2, 3, 5, 7, 8, 9, 12, 13, 16, 17, 18, 19, 20). In drug-to-target modeling studies, we predicted a common binding mode of meriolin 16 and 36 to the ATP-pocket of CDK2 and an additional flipped binding for meriolin 36. We could show that cell cycle progression and proliferation were blocked by abolishing phosphorylation of retinoblastoma protein (a major target of CDK2) at Ser612 and Thr82. Moreover, meriolin 16 prevented the CDK9-mediated phosphorylation of RNA polymerase II at Ser2 which is crucial for transcription initiation. This renders both meriolin derivatives as valuable anticancer drugs as they target three different Achilles’ heels of the tumor: (1) inhibition of cell cycle progression and proliferation, (2) prevention of transcription, and (3) induction of cell death.

Discrete Trial Training (DTT) is a method of intervention for individuals with Autism Spectrum Disorder (ASD). Applications of DTT require prescribed repetitions of instruction. DTT is typically implemented via trained instructors or teachers. However, prior analysis has demonstrated the potential of parent-implemented DTT. Prior research demonstrated that DTT training can be implemented with a high degree of fidelity using a student teacher population. However, to date, no studies have evaluated the use of a DTT telehealth training with parents of children with ASD. The purpose of this study was to evaluate the feasibility of a remote parent training method to allow parents to implement DTT in home settings. To this end, three parent participants of children diagnosed with ASD were trained to implement DTT through a telehealth modality in a nonconcurrent multiple baseline design. Results suggested efficacy of this method at DTT skills acquisition.

IntroductionData on the increase in mortality during the COVID-19 pandemic based on individuals' socioeconomic positions are limited. This study examines this increase in mortality in Spain during the epidemic waves of 2020 and 2021.MethodsWe calculated the overall and cause-specific mortality rates during the 2017–2019 pre-pandemic period and four epidemic periods in 2020 and 2021 (first, second, third-fourth, and fifth-sixth waves). Mortality rates were analyzed based on educational levels (low, medium, and high) and across various age groups (25–64, 65–74, and 75+). The increase in mortality during each epidemic period compared to the pre-pandemic period was estimated using mortality rate ratios (MRR) derived from Poisson regression models.ResultsAn inverse educational gradient in overall mortality was observed across all periods; however, this pattern was not consistent for COVID-19 mortality in some age groups. Among those aged 75 years and older, highly educated individuals showed higher COVID-19 mortality during the first wave. In the 25–64 age group, individuals with low education experienced the highest overall mortality increase, while those with high education had the lowest increase. The MRRs were 1.21 and 1.06 during the first wave and 1.12 and 0.97 during the last epidemic period. In the 65–74 age group, highly educated individuals showed the highest overall mortality increase during the first wave, whereas medium-educated individuals had the highest increase during the subsequent epidemic periods. Among those aged 75 and older, highly educated individuals exhibited the highest overall mortality increase while the individuals with low education showed the lowest overall mortality increment, except during the last epidemic period.ConclusionThe varying educational patterns of COVID-19 mortality across different age groups contributed to the disparities of findings in increased overall mortality by education levels during the COVID-19 pandemic.

We study the behavior across the deconfinement phase transition of the chro-moelectric flux tube generated by a static quark and a static antiquark for several distances between them. We present preliminary results for distances up to 1.33 fm and temperatures up to 1.5Tc.

Abstract This paper examines the ethical and legal challenges encountered during the GATEKEEPER Project and how these challenges informed the development of a comprehensive framework for future Large-Scale Pilot (LSP) projects. GATEKEEPER is a LSP Project with 48 partners conducting 30 implementation studies across Europe with 50,000 target participants grouped into 9 Reference Use Cases. The project underscored the complexity of obtaining ethical approval across various jurisdictions with divergent regulations and procedures. Through a detailed analysis of the issues faced and the strategies employed to navigate these challenges, this study proposes an ethical and legal framework. This framework, derived from a comparative analysis of ethical application forms and regulations, aims to streamline the ethical approval process for future LSP research projects. By addressing the hurdles encountered in GATEKEEPER, the proposed framework offers a roadmap for more efficient and effective project management, ensuring smoother implementation of similar projects in the future.

Abstract Pregnant women might have an increased risk of SARS-COV-2 infection. Although evidence towards the efficacy and safety of COVID-19 is growing still there is room for improvement on the knowledge towards pregnancy adverse events, such as miscarriage. We explored the association of COVID-19 vaccine with the risk of miscarriages using the Real-World. We identified a cohort of vaccinated pregnancies using the BIFAP database which contains systematically recorded data on care patients in Spain (N = 4054). We then restricted it to those women who had a miscarriage using a validated algorithm (N = 607). Among them, we performed a case-crossover design to evaluate the effect of intermittent exposures on the risk of miscarriage. Adjusted Odds Ratio with their confidence intervals were calculated using two analytical approaches: conditional logistic regression and Generalized Linear Mixed-Effects Models. A total of 225 (37.1%) were aged 35–39 years. The most common comorbidities were asthma, migraine, gastritis, and hypothyroidism. A total of 14.7% received only one dose of COVID-19 and 85.3% two doses, respectively. A total of 36.8% of women with one dose and 27.6% with two doses received the vaccine 7 days prior to the miscarriage. Corresponding adjusted estimates for the risk of miscarriage using the conditional logistic regression where as follows: 1.65 (95% CI 0.85–3.23) when using as the sum of 3 control moments among women with one dose, 1.02 (95% CI 0.72–1.46) among women with two doses and 1.03 (95% CI 0.72, 1.46) using the whole study population. Very similar results were obtained when conducting the Generalized Linear Mixed-Effects Models. There was no overall increased risk of miscarriage onset associated with COVID-19 vaccine although contradictory results were found according to the number of doses. Further studies are required with larger sample sizes to assess this association.

Abstract Background The immune system has a central role in preventing carcinogenesis. Alteration of systemic immune cell levels may increase cancer risk. However, the extent to which common genetic variation influences blood traits and cancer risk remains largely undetermined. Here, we identify pleiotropic variants and predict their underlying molecular and cellular alterations. Methods Multivariate Cox regression was used to evaluate associations between blood traits and cancer diagnosis in cases in the UK Biobank. Shared genetic variants were identified from the summary statistics of the genome-wide association studies of 27 blood traits and 27 cancer types and subtypes, applying the conditional/conjunctional false-discovery rate approach. Analysis of genomic positions, expression quantitative trait loci, enhancers, regulatory marks, functionally defined gene sets, and bulk- and single-cell expression profiles predicted the biological impact of pleiotropic variants. Plasma small RNAs were sequenced to assess association with cancer diagnosis. Results The study identified 4093 common genetic variants, involving 1248 gene loci, that contributed to blood–cancer pleiotropism. Genomic hotspots of pleiotropism include chromosomal regions 5p15-TERT and 6p21-HLA. Genes whose products are involved in regulating telomere length are found to be enriched in pleiotropic variants. Pleiotropic gene candidates are frequently linked to transcriptional programs that regulate hematopoiesis and define progenitor cell states of immune system development. Perturbation of the myeloid lineage is indicated by pleiotropic associations with defined master regulators and cell alterations. Eosinophil count is inversely associated with cancer risk. A high frequency of pleiotropic associations is also centered on the regulation of small noncoding Y-RNAs. Predicted pleiotropic Y-RNAs show specific regulatory marks and are overabundant in the normal tissue and blood of cancer patients. Analysis of plasma small RNAs in women who developed breast cancer indicates there is an overabundance of Y-RNA preceding neoplasm diagnosis. Conclusions This study reveals extensive pleiotropism between blood traits and cancer risk. Pleiotropism is linked to factors and processes involved in hematopoietic development and immune system function, including components of the major histocompatibility complexes, and regulators of telomere length and myeloid lineage. Deregulation of Y-RNAs is also associated with pleiotropism. Overexpression of these elements might indicate increased cancer risk.

IntroductionUnderstanding the adaptive capacity to current climate change of drought-sensitive tree species is mandatory, given their limited prospect of migration and adaptation as long-lived, sessile organisms. Knowledge about the molecular and eco-physiological mechanisms that control drought resilience is thus key, since water shortage appears as one of the main abiotic factors threatening forests ecosystems. However, our current background is scarce, especially in conifers, due to their huge and complex genomes.MethodsHere we investigated the eco-physiological and transcriptomic basis of drought response of the climate change-threatened conifer Cedrus atlantica. We studied C. atlantica seedlings from two locations with contrasting drought conditions to investigate a local adaptation. Seedlings were subjected to experimental drought conditions, and were monitored at immediate (24 hours) and extended (20 days) times. In addition, post-drought recovery was investigated, depicting two contrasting responses in both locations (drought resilient and non-resilient). Single nucleotide polymorphisms (SNPs) were also studied to characterize the genomic basis of drought resilience and investigate a rapid local adaptation of C. atlantica.ResultsDe novo transcriptome assembly was performed for the first time in this species, providing differences in gene expression between the immediate and extended treatments, as well as among the post-drought recovery phenotypes. Weighted gene co-expression network analysis showed a regulation of stomatal closing and photosynthetic activity during the immediate drought, consistent with an isohydric dynamic. During the extended drought, growth and flavonoid biosynthesis inhibition mechanisms prevailed, probably to increase root-to-shoot ratio and to limit the energy-intensive biosynthesis of secondary metabolites. Drought sensitive individuals failed in metabolism and photosynthesis regulation under drought stress, and in limiting secondary metabolite production. Moreover, genomic differences (SNPs) were found between drought resilient and sensitive seedlings, and between the two studied locations, which were mostly related to transposable elements.DiscussionThis work provides novel insights into the transcriptomic basis of drought response of C. atlantica, a set of candidate genes mechanistically involved in its drought sensitivity and evidence of a rapid local adaptation. Our results may help guide conservation programs for this threatened conifer, contribute to advance drought-resilience research and shed light on trees' adaptive potential to current climate change.

Abstract Epidermal electrophysiology is a non‐invasive method used in research and clinical practices to study the electrical activity of the brain, heart, nerves, and muscles. However, electrode/tissue interlayer materials such as ionically conducting pastes can negatively affect recordings by introducing lateral electrode‐to‐electrode ionic crosstalk and reducing spatial resolution. To overcome this issue, biocompatible, anisotropic‐conducting interlayer composites (ACI) that establish an electrically anisotropic interface with the skin are developed, enabling the application of dense cutaneous sensor arrays. High‐density, conformable electrodes are also microfabricated that adhere to the ACI and follow the curvilinear surface of the skin. The results show that ACI significantly enhances the spatial resolution of epidermal electromyography (EMG) recording compared to conductive paste, permitting the acquisition of single muscle action potentials with distinct spatial profiles. The high‐density EMG in developing mice, non‐human primates, and humans is validated. Overall, high spatial‐resolution epidermal electrophysiology enabled by ACI has the potential to advance clinical diagnostics of motor system disorders and enhance data quality for human‐computer interface applications.

Metastatic colorectal cancer (mCRC) currently lacks reliable biomarkers for precision medicine, particularly for chemotherapy-based treatments. This study examines the behavior of 11 CXC chemokines in the blood of 104 mCRC patients undergoing first-line oxaliplatin-based treatment to pinpoint predictive and prognostic markers. Serum samples were collected before treatment, at response evaluation (EVAR), and at disease progression or last follow-up. Chemokines were assessed in all samples using a Luminex® custom panel. CXCL13 levels increased at EVAR in responders, while in non-responders it decreased. Increasing levels of CXCL13 at EVAR, independently correlated with improved progression-free survival (PFS) and overall survival (OS). Nanostring® analysis in primary tumor samples showed CXCL13 gene expression's positive correlation not only with gene profiles related to an immunogenic tumor microenvironment, increased B cells and T cells (mainly CD8+) but also with extended OS. In silico analysis using RNAseq data from liver metastases treated or not with neoadjuvant oxaliplatin-based combinations, and deconvolution analysis using the MCP-counter algorithm, confirmed CXCL13 gene expression's association with increased immune infiltration, improved OS, and Tertiary Lymphoid Structures (TLSs) gene signatures, especially in neoadjuvant-treated patients. CXCL13 analysis in serum from 36 oxaliplatin-treated patients from the METIMMOX study control arm, reported similar findings. In conclusion, the increase of CXCL13 levels in peripheral blood and its association with the formation of TLSs within the metastatic lesions, emerges as a potential biomarker indicative of the therapeutic efficacy in mCRC patients undergoing oxaliplatin-based treatment

Abstract Attaining precise control over molecular arrangements is of paramount importance for numerous applications in nanotechnology, particularly in constructing molecular templates to accurately immobilize target materials on surfaces. A strategic combination of supramolecular and interfacial chemistry may serve to build a well‐organized molecular network, enabling the subsequent location of target molecules on specific positions of a surface. A supramolecular complex (compound 1) comprised of a melamine unit forming hydrogen bonds with dendritic arms terminated in a coumarin unit is utilized, which readily undergoes photodimerization. The research demonstrates the formation of well‐organized Langmuir films of compound 1 which can be transferred on substrates at low surface pressures adopting a lying‐flat orientation. Upon irradiation of the pristine films at 365 nm the coumarin units undergo photo‐cross linking, leading to the formation of a compact photo‐crosslinked film. Incubation of these photo‐crosslinked films in a solution containing 1‐hexanethiol results in the withdrawal of the melamine and the chemisorption of two thiol molecules per each melamine unit. The nanopores created by the removal of the melamine core are attributed to the disruption of hydrogen bonds in compound 1 by the thiols. This precisely defined molecular network holds significant promise as a template for orchestrating the arrangement of functional materials on surfaces.

ObjectivesPrecise HDV-RNA detection and quantification are pivotal for diagnosis and monitoring of response to newly approved treatment. We evaluate the performance of three HDV RNA detection and quantification assays.MethodsHepatitis Delta RT-PCR system kit, EurobioPlex HDV assay, and RoboGene HDV RNA Quantification kit 2.0 were used for testing 151 HBsAg-positive samples, 90 HDV-RNA negative and 61 HDV-RNA positive. We also evaluated serial dilutions of the WHO international standard for HDV, PEI 7657/12. All HDV-RNA positive samples were genotyped using a next-generation sequencing strategy.ResultsQualitative results indicated a 100% concordance between tests. Quantitative results correlated well, r2 = 0.703 (Vircell-vs-Eurobio), r2 = 0.833 (Vircell-vs-RoboGene), r2 = 0.835 (Robogene-vs-Eurobio). Bias index was 2.083 (Vircell-vs-Eurobio), -1.283 (Vircell-vs-RoboGene), and -3.36 (Robogene-vs-Eurobio). Using the WHO IS, Vircell overestimated the viral load by 0.98 log IU/mL, Eurobio by 1.46 log IU/mL, and RoboGene underestimated it by 0.98 log IU/mL. Fifty-nine samples were successfully genotyped (Genotype 1, n=52; Genotype 5, n=7; Genotype 6, n=1), with similar results for correlation and bias.ConclusionThis study underscores the necessity of using reliable HDV-RNA detection and quantification assays, as evidenced by the high concordance rates in qualitative detection and the observed variability in quantitative results. These findings highlight the importance of consistent assay use in clinical practice to ensure accurate diagnosis and effective treatment monitoring of HDV infection.

People with chronic cough (a cough lasting more than 8 weeks) are often referred to different specialists and undergo numerous diagnostic tests, but clear guidance is lacking. This work summarizes a consensus (an agreement) among medical specialists who are involved in managing people with chronic cough : primary care physicians (family doctors), pulmonologists (doctors who specialize in lung conditions), allergists (medical professionals specializing in allergies) and ear, nose and throat (ENT) specialists. They discussed how to perform a basic assessment of people with chronic cough in primary care (day-to-day healthcare given by a general practitioner or family doctor) and how to refer them to different specialists based on clinical findings or test results.

Within the European Union, the pluralist polarized journalistic model suggests the presence of journalistic cultures rooted in the connections between political parties and media organizations. In this classical framework, the state exerts significant intervention to influence a media system characterized by lower levels of professionalization. In this regard, Spain serves as a well-examined example of a pluralist polarized Western democracy. Our study entails a systematic review based on two distinct dimensions. Firstly, we scrutinized all legal documents pertaining to media regulation in Spain published between the Spanish transition and the present 1977–2024. From this perspective, we propose a chronological evolution to categorize this extensive collection of norms. Secondly, we complement our primary source assessment with an examination of secondary sources to validate the proposed evolution. Our findings indicate that the Spanish media regulation is evolving due to two pivotal factors: the influence of the European Union and the preservation of the narrative established during the transition to democracy. While contemporary communication grapples with issues such as the rise of artificial intelligence, journalistic instability, algorithmic communication, and fragmented user consumption, these areas are only addressed peripherally within the Spanish media normative context.