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ACADEMIC ABSTRACT: In the wake of the replication crisis, social and personality psychologists have increased attention to power analysis and the adequacy of sample sizes. In this article, we analyze current controversies in this area, including choosing effect sizes, why and whether power analyses should be conducted on already-collected data, how to mitigate the negative effects of sample size criteria on specific kinds of research, and which power criterion to use. For novel research questions, we advocate that researchers base sample sizes on effects that are likely to be cost-effective for other people to implement (in applied settings) or to study (in basic research settings), given the limitations of interest-based minimums or field-wide effect sizes. We discuss two alternatives to power analysis, precision analysis and sequential analysis, and end with recommendations for improving the practices of researchers, reviewers, and journal editors in social-personality psychology. PUBLIC ABSTRACT: Recently, social-personality psychology has been criticized for basing some of its conclusions on studies with low numbers of participants. As a result, power analysis, a mathematical way to ensure that a study has enough participants to reliably "detect" a given size of psychological effect, has become popular. This article describes power analysis and discusses some controversies about it, including how researchers should derive assumptions about effect size, and how the requirements of power analysis can be applied without harming research on hard-to-reach and marginalized communities. For novel research questions, we advocate that researchers base sample sizes on effects that are likely to be cost-effective for other people to implement (in applied settings) or to study (in basic research settings). We discuss two alternatives to power analysis, precision analysis and sequential analysis, and end with recommendations for improving the practices of researchers, reviewers, and journal editors in social-personality psychology.

Sr. Editor: Las lesiones coronarias calcificadas siguen siendo un desafío clínico a la hora de realizar intervenciones, ya que se asociana índices más altos de complicaciones como infraexpansión y mala aposición del stent. Esto conlleva un mayor riesgo de revascularización de la lesión diana (RLD), trombosis del stent, infarto de miocardio (IM) y muerte1. Mientras que los stents farmacoactivos (SFA) de última generación y los dispositivos contemporáneos son más seguros y efectivos, sigue siendo necesario recurrir a técnicas de modificación de la placa ateroesclerótica para una adecuada expansión y aposición de dichos stents cuando fracasan las técnicas convencionales. Los balones de corte están diseñados para tratar lesiones complejas, como placas fibróticas y lesiones calcificadas2,3; no obstante, su uso puede haberse visto limitado por su peor perfil de cruce y poca evidencia que avale su perfil de eficacia y seguridad4. Además, la literatura publicada disponible se basa en estudios con diseños de no inferioridad y tamaños de muestra pequeños5 y no en análisis con la suficiente potencia estadística como para poder valorar la eficacia clínica de los balones de corte en pacientes con enfermedad coronaria (EC) de vaso nativo. En este sentido, se realizó una revisión sistemática y metanálisis para llevar a...

To the Editor, Calcified coronary lesions remain a procedural and clinical challenge associated with higher rates of procedural complications such as stent underexpansion and malapposition leading to an increased risk of target lesion revascularization (TLR), stent thrombosis, myocardial infarction (MI), and death.1 While newer drug-eluting stents and advanced devices are considered safer and more effective, there is still a need for atherosclerotic plaque modification techniques that allow for adequate stent expansion and apposition when traditional techniques fail. Cutting and scoring balloons have been designed to treat complex lesions such as fibrotic plaque and calcified lesions.2,3 However, their use may have been limited by problems of crossability and limited evidence supporting their efficacy and safety.4 In addition, the available published literature is based on studies with noninferiority designs and small sample sizes,5 which may not provide adequately powered analyses to evaluate the clinical efficacy of cutting and scoring balloons in patients with native-vessel coronary artery disease (CAD). Therefore, we performed a systematic review and meta-analysis to compare cutting and scoring balloons with conventional balloons (semi- and non-compliant balloons) in patients with native vessel CAD. This meta-analysis was conducted according to the PRISMA guidelines for the reporting of systematic reviews. Two reviewers independently identified...

ABSTRACT Introduction and objectives: Although drug-eluting stents are the main treatment in percutaneous coronary interventions (PCI), drug-coated balloons (DCB) represent an appealing alternative as they eliminate the risk of stent thrombosis and avoid leaving any metal structure in the vessel wall. However, limited evidence has been published to date on the vessel wall healing processes, plaque remodeling, plaque composition, and the impact on the coronary microcirculation after percutaneous coronary intervention with DCB (DCB-PCI). Methods: This is investigator-initiated, single-center, single-arm, open-label, pilot study of 30 patients with native vessel disease undergoing DCB-PCI. Intravascular ultrasound and angiography-derived index of microvascular resistance (IMRangio) will be performed before and immediately after PCI, and at 3 months of follow-up. Conclusions: The study aims to provide new evidence on the modification of atherosclerotic plaque in patients with de novo lesions undergoing PCI with DCB. This will be assessed by examining the change in the percentage of atheroma volume and late lumen enlargement using intravascular ultrasound and by evaluating changes in the microcirculation using IMRangio. Registered at Clinicaltrials.gov (NCT06080919). Keywords: Drug-coated balloon. Intravascular ultrasound. Angiography-derived index of microvascular resistance. RESUMEN Introducción y objetivos: Pese a que los stents farmacoactivos son el tratamiento principal en las angioplastias coronarias, los balones farmacoactivos representan una alternativa interesante dado...

RESUMEN Introducción y objetivos: Pese a que los stents farmacoactivos son el tratamiento principal en las angioplastias coronarias, los balones farmacoactivos representan una alternativa interesante dado que eliminan el riesgo de trombosis del stent sin dejar ningún tipo de estructura metálica en la pared del vaso. No obstante, la evidencia en cuanto a los procesos de cicatrización de la pared del vaso, el remodelado, los cambios en la composición de la placa ateroesclerótica y el impacto en la microcirculación coronaria tras el intervencionismo coronario percutáneo (ICP) con balón farmacoactivo aún no se ha esclarecido. Métodos: Estudio piloto abierto, de un solo grupo, iniciado por el investigador, de 30 pacientes con enfermedad de vaso nativo sometidos a ICP con balón farmacoactivo. Se realizará ecografía intravascular y se determinará el índice de resistencia microvascular derivado de la angiografía (angio-IRM) antes, inmediatamente después y a los 3 meses de seguimiento de la angioplastia. Conclusiones: Se aportará nueva evidencia sobre la modificación de la placa en pacientes con enfermedad de vaso nativo tratados con balón farmacoactivo, evaluando el cambio en el porcentaje del volumen de ateroma y el aumento luminal tardío, así como los cambios en la microcirculación mediante angio-IRM. Registrado en Clinicaltrials.gov (NCT06080919).

Moral reframing is a communication technique that involves persuading an audience to support an issue they typically oppose on ideological grounds by appealing to concepts and values that align with their moral concerns. Overall, previous research has found that moral reframing can encourage attitude change more so than non-reframed messages. One pending question, though, is whether people would or would not use this technique in the first place (e.g., because it requires embracing values that one might not endorse). This online study (N = 249) tested the willingness of US-based liberals to use a message appealing to conservative values (morally reframed), vs. one appealing to liberal values (not morally reframed), to persuade a hypothetical conservative audience to be more pro-environmental. Reasons behind message choice and feelings about both messages were measured. Results showed that most participants chose to use the morally reframed message (73%). This choice was justified by the message’s perceived effectiveness, while rejecting it was justified by the need to feel true to one’s own beliefs and values. However, regardless of actual message choice, participants overall reported more positive and less negative integrity feelings for the message that was not morally reframed.

Emotions are linked to wide sets of action tendencies, and it can be difficult to predict which specific action tendency will be motivated or indulged in response to individual experiences of emotion. Building on a functional perspective of emotion, we investigate whether anger and shame connect to different behavioral intentions in dignity, face, and honor cultures. Using simple animations that showed perpetrators taking resources from victims, we conducted two studies across eleven countries investigating the extent to which participants expected victims to feel anger and shame, how they thought victims should respond to such violations, and how expectations of emotions were affected by enacted behavior. Across cultures, anger was associated with desires to reclaim resources or alert others to the violation. In face and honor cultures, but not dignity cultures, shame was associated with the desire for aggressive retaliation. However, we found that when victims indulged motivationally-relevant behavior, expected anger and shame were reduced, and satisfaction increased, in similar ways across cultures. Results suggest similarities and differences in expectations of how emotions functionally elicit behavioral responses across cultures.

Our choice to withhold or disclose displeasing information to another can motivate concern about damage to our social bonds. In two experiments, using two different samples of university students in Norway, (N = 174 and N = 217), we found that withholding unpleasant information led to greater concern for self- image and social-image than did disclosure. We also found that withholding elicited more shame, inferiority and rejection than disclosure, and in Experiment 2, withholding elicited more defensive motivation than disclosure. Consistent with our model, defensive motivation was mostly explained by concern for social-image, whereas relationship repair motivation was mostly explained by concern for self-image and felt shame. We discuss implications for the literature on shame and social bonds., Author(s): Stine Torp Løkkeberg [sup.1] , Nicolay Gausel [sup.1] , Roger Giner-Sorolla [sup.2] , Colin Wayne Leach [sup.3] [sup.4] Author Affiliations: (1) grid.446040.2, 0000 0001 1940 9648, Faculty of Health [...]

Aragonese is a threatened Romance language immersed in a historical process of substitution by Spanish, the official language. The number of speakers who maintained its transmission to younger generations, mainly in rural areas, has extremely declined over the last century. In the meantime, revitalisation efforts have incorporated new speakers, especially in urban areas. Due to a weak and conflicting standardisation and institutionalisation of the language, as in other threatened languages, the new speakers are located between three poles: the supremacist position of the official language; the authenticity position highlighting the native varieties; or the legitimisation of supralocal varieties in a context with a hierarchical and conflicted management of revitalisation. The analysis of the interviews allows us to categorise the discourses and establish profiles of new speakers, according to their ideologies and declared practices. The results show a polarisation of the urban new speakers' discourses, with disputes about the legitimacy of supralocal varieties, the contact with native speakers, or the forms of acquisition of the language. All these questions converge in the central academic debate about the Aragonese as a threatened language, and the new speakers and the proactivity not only as the future of the language, but also as its present.

Abstract Epithelial‐mesenchymal transition (EMT) is a reversible transcriptional program invoked by cancer cells to drive cancer progression. Transcription factor ZEB1 is a master regulator of EMT, driving disease recurrence in poor‐outcome triple negative breast cancers (TNBCs). Here, this work silences ZEB1 in TNBC models by CRISPR/dCas9‐mediated epigenetic editing, resulting in highly‐specific and nearly complete suppression of ZEB1 in vivo, accompanied by long‐lasting tumor inhibition. Integrated “omic” changes promoted by dCas9 linked to the KRAB domain (dCas9‐KRAB) enabled the discovery of a ZEB1‐dependent‐signature of 26 genes differentially‐expressed and ‐methylated, including the reactivation and enhanced chromatin accessibility in cell adhesion loci, outlining epigenetic reprogramming toward a more epithelial state. In the ZEB1 locus transcriptional silencing is associated with induction of locally‐spread heterochromatin, significant changes in DNA methylation at specific CpGs, gain of H3K9me3, and a near complete erasure of H3K4me3 in the ZEB1 promoter. Epigenetic shifts induced by ZEB1‐silencing are enriched in a subset of human breast tumors, illuminating a clinically‐relevant hybrid‐like state. Thus, the synthetic epi‐silencing of ZEB1 induces stable “lock‐in” epigenetic reprogramming of mesenchymal tumors associated with a distinct and stable epigenetic landscape. This work outlines epigenome‐engineering approaches for reversing EMT and customizable precision molecular oncology approaches for targeting poor outcome breast cancers.

Summary: Fractional flow reserve (FFR)-guided percutaneous coronary intervention (PCI) is recommended in revascularization guidelines for intermediate lesions. However, recent studies comparing FFR-guided PCI with non-physiology-guided revascularization have reported conflicting results. PubMed and Embase were searched for studies comparing FFR-guided PCI with non-physiology-guided revascularization strategies (angiography-guided, intracoronary imaging-guided, coronary artery bypass grafting). Data were pooled by meta-analysis using random-effects model. 26 studies enrolling 78,897 patients were included. FFR-guided PCI as compared to non-physiology-guided coronary revascularization had lower risk of all-cause mortality (odds ratio [OR] 0.79 95% confidence interval [CI] 0.64–0.99, I2 = 53%) and myocardial infarction (MI) (OR 0.74 95% CI 0.59–0.93, I2 = 44.7%). However, no differences between groups were found in terms of major adverse cardiac events (MACEs) (OR 0.86 95% CI 0.72–1.03, I2 = 72.3%) and repeat revascularization (OR 1 95% CI 0.82–1.20, I2 = 43.2%). Among patients with coronary artery disease (CAD), FFR-guided PCI as compared to non-physiology-guided revascularization was associated with a lower risk of all-cause mortality and MI.

Despite decades of study, the molecular mechanisms and selectivity of the biomolecular components of honeybee (Apis mellifera) venom as anticancer agents remain largely unknown. Here, we demonstrate that honeybee venom and its major component melittin potently induce cell death, particularly in the aggressive triple-negative and HER2-enriched breast cancer subtypes. Honeybee venom and melittin suppress the activation of EGFR and HER2 by interfering with the phosphorylation of these receptors in the plasma membrane of breast carcinoma cells. Mutational studies reveal that a positively charged C-terminal melittin sequence mediates plasma membrane interaction and anticancer activity. Engineering of an RGD motif further enhances targeting of melittin to malignant cells with minimal toxicity to normal cells. Lastly, administration of melittin enhances the effect of docetaxel in suppressing breast tumor growth in an allograft model. Our work unveils a molecular mechanism underpinning the anticancer selectivity of melittin, and outlines treatment strategies to target aggressive breast cancers.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

We present a consensus-based checklist to improve and document the transparency of research reports in social and behavioural research. An accompanying online application allows users to complete the form and generate a report that they can submit with their manuscript or post to a public repository.

Abstract Respiratory viral infections (RVIs) are frequent in preterm infants possibly inducing long-term impact on respiratory morbidity. Immune response and respiratory barriers are key defense elements against viral insults in premature infants admitted to Neonatal Intensive Care Units (NICUs). Our main goals were to describe the local immune response in respiratory secretions of preterm infants with RVIs during NICU admission and to evaluate the expression and synthesis of lung barrier regulators, both in respiratory samples and in vitro models. Samples from preterm infants that went on to develop RVIs had lower filaggrin gene and protein levels at a cellular level were compared to never-infected neonates (controls). Filaggrin, MIP-1α/CCL3 and MCP-1 levels were higher in pre-infection supernatants compared to controls. Filaggrin, HIF-1α, VEGF, RANTES/CCL5, IL-17A, IL-1β, MIP-1α and MIP-1β/CCL5 levels were higher during and after infection. ROC curve and logistic regression analysis shows that these molecules could be used as infection risk biomarkers. Small airway epithelial cells stimulated by poly:IC presented reduced filaggrin gene expression and increased levels in supernatant. We conclude that filaggrin gene and protein dysregulation is a risk factor of RVI in newborns admitted at the NICU.

The sensitivity of pleural fluid (PF) analyses for the diagnosis of malignant pleural effusions (MPEs) is low to moderate. Knowledge about the pathobiology and molecular characteristics of this condition is limited. In this study, the crosstalk between stromal cells and tumor cells was investigated in vitro in order to reveal factors that are present in PF which can mediate MPE formation and aid in discriminating between benign and malignant etiologies. Eighteen PF samples, in different proportions, were exposed in vitro to mesothelial MeT-5A cells to determine the biological effects on these cells. Treatment of normal mesothelial MeT-5A cells with malignant PF increased cell viability, proliferation, and migration, and activated different survival-related signaling pathways. We identified differentially expressed miRNAs in PF samples that could be responsible for these changes. Consistently, bioinformatics analysis revealed an enrichment of the discovered miRNAs in migration-related processes. Notably, the abundance of three miRNAs (miR-141-3p, miR-203a-3, and miR-200c-3p) correctly classified MPEs with false-negative cytological examination results, indicating the potential of these molecules for improving diagnosis. Malignant PF produces phenotypic and functional changes in normal mesothelial cells. These changes are partly mediated by certain miRNAs, which, in turn, could serve to differentiate malignant from benign effusions.

(1) Background: Eosinophilia has traditionally been linked to eosinophilic asthma, for which it is the gold-standard prognostic biomarker. However, the association between eosinophilia and the presence of other diseases and comorbidities is yet unclear. (2) Methods: For this retrospective study, we reviewed the electronic medical records of 49,909 subjects with blood eosinophilia to gather data on the presence of asthma, COPD, sleep apnea, tuberculosis, dyslipidemia, hypertension, and other cardiovascular diseases and severe CRSwNP among these subjects. Demographic features including age, sex, and smoking habits were collected, as well as the number of hospitalizations and emergency department visits. T-tests, ANOVA, Fisher test, and logistic regression models were used. (3) Results: For all age groups studied, eosinophilia was significantly more prevalent among asthmatic subjects than nonasthmatics, especially in patients also presenting CRSwNP, hypertension, and dyslipidemia. The likelihood of developing asthma, COPD, and CRSwNP, and hospitalization, was increased when BEC was above 600 eosinophils/μL. The association between asthma, CRSwNP, and BEC was corroborated by multiple logistic regressions models. (4) Conclusions: We demonstrated the association of having over 600 blood eosinophils/μL with a higher number of hospitalizations and comorbidities (CRSwNP and COPD), which proves that BEC is a highly useful parameter to consider in subjects who present blood eosinophilia.

Leather finishing is a critical process in the leather industry, as it significantly influences the final appearance, durability, and quality of leather products. Traditional leather finishing techniques often involve the use of synthetic chemicals, which may lead to environmental concerns and potential health hazards. In this study, we investigate the feasibility and effectiveness of a new collagen-based product for leather finishing. Collagen, a natural protein found abundantly in animals, has shown promise as an environmentally friendly and sustainable alternative for leather finishing. The new collagen gel product obtained from bovine hide waste by using an alkaline extraction method with lime was functionalized through an enzymatic treatment that allows to achieve a finishing product suitable for coating formulations, and at the same time, a biodegradable finishing. The collagen gel product was optimized by varying parameters, such as temperature, pH, and enzyme quantity. The optimized collagen gel product exhibits a wide particle size range and retains the triple-helical structure of collagen. The leather samples treated with the collagen gel product show enhanced properties compared to those with conventional finishes. The results show that the collagen gel product enhances water vapor permeability, color stability, and touch in the finishes. However, a low resistance to wet rubbing is obtained; therefore, it is necessary to study how to improve this parameter.

The need for advances in the management/treatment options for ischemic stroke patients requires that upcoming preclinical research uses animals with more human-like brain characteristics. The porcine brain is considered appropriate, although the presence of the rete mirabile (RM) prevents direct catheterization of the intracranial arteries to produce focal cerebral ischemia. To develop a reproducible minimally invasive porcine stroke model, a guide catheter and guide wire were introduced through the femoral artery until reaching the left RM. Using the pressure cooker technique, Squid-12 embolization material was deposited to fill, overflow, and occlude the left RM, the left internal carotid artery, and left circle of Willis wing up to the origins of the middle cerebral arteries (MCAs), mimicking the occlusion produced in the filament model in rodents. Longitudinal multimodal cerebral MRI was conducted to assess the brain damage and cerebral blood supply. The technique we describe here occluded up to the origins of the MCAs in 7 of 8 swine, inducing early damage 90 minutes after occlusion that later evolved to a large cerebral infarction and producing no mortality during the intervention. This minimally invasive ischemic stroke model in swine produced reproducible infarcts and shows translational features common to human stroke.

Increased execution of replication studies contributes to the effort to restore credibility of empirical research. However, a second generation of problems arises: the number of potential replication targets is at a serious mismatch with available resources. Given limited resources, replication target selection should be well-justified, systematic and transparently communicated. At present the discussion on what to consider when selecting a replication target is limited to theoretical discussion, self-reported justifications and a few formalized suggestions. In this Registered Report, we proposed a study involving the scientific community to create a list of considerations for consultation when selecting a replication target in psychology. We employed a modified Delphi approach. First, we constructed a preliminary list of considerations. Second, we surveyed psychologists who previously selected a replication target with regards to their considerations. Third, we incorporated the results into the preliminary list of considerations and sent the updated list to a group of individuals knowledgeable about concerns regarding replication target selection. Over the course of several rounds, we established consensus regarding what to consider when selecting a replication target. The resulting checklist can be used for transparently communicating the rationale for selecting studies for replication.

Metastasis is the leading cause of colorectal cancer (CRC)-related deaths. Therefore, the identification of accurate biomarkers predictive of metastasis is needed to better stratify high-risk patients to provide preferred management and reduce mortality. In this study, we identified 13 new genes that modified circulating tumor cell numbers using a genome-wide genetic screen in a whole animal CRC model. Candidate genes were subsequently evaluated at the gene expression level in both an internal human CRC cohort of 153 patients and an independent cohort from the TCGA including 592 patients. Interestingly, the expression of one candidate, PLA2G12A, significantly correlated with both the time to recurrence and overall survival in our CRC cohort, with its low expression being an indicator of a poor clinical outcome. By examining the TCGA cohort, we also found that low expression of PLA2G12A was significantly enriched in epithelial–mesenchymal transition signatures. Finally, the candidate functionality was validated in vitro using three different colon cancer cell lines, revealing that PLA2G12A deficiency increases cell proliferation, migration, and invasion. Overall, our study identifies PLA2G12A as a prognostic biomarker of early-stage CRC, providing evidence that its deficiency promotes tumor growth and dissemination.

Abstract Aims Heart failure (HF) is a proinflammatory disease often associated with the onset of iron deficiency (ID). ID alters mitochondrial function, reducing the generation of cellular energy in skeletal muscle and cardiomyocytes. This study aimed to analyse the response of patients with HF to intravenous iron administration according to the type of HF: preserved ejection fraction (HFpEF) or reduced ejection fraction (HFrEF). Methods and results We conducted a retrospective, single‐centre study of 565 consecutive outpatients diagnosed with HF, recruited over 5 years, who were given intravenous ferric carboxymaltose (FCM) for the treatment of ID [defined as ferritin 0.05). Conclusions Intravenous iron administration appeared to improve ejection fraction and cardiac functional status in outpatients with ID and HF with both preserved and reduced ejection fraction.

We have previously demonstrated that the post-stroke administration of iron-free transferrin (apotransferrin, ATf) is beneficial in different models of ischemic stroke (IS) through the inhibition of the neuronal uptake of pro-oxidant iron. In the present study, we asked whether ATf is safe and also beneficial when given after the induction of intracerebral hemorrhage (ICH) in mice, and investigated the underlying mechanisms. We first compared the main iron actors in the brain of IS- or collagenase-induced ICH mice and then obtained insight into these iron-related proteins in ICH 72 h after the administration of ATf. The infarct size of the IS mice was double that of hemorrhage in ICH mice, but both groups showed similar body weight loss, edema, and increased ferritin and transferrin levels in the ipsilateral brain hemisphere. Although the administration of human ATf (hATf) to ICH mice did not alter the hemorrhage volume or levels of the classical ferroptosis GPX4/system xc- pathways, hATf induced better neurobehavioral performance, decreased 4-hydroxynonenal levels and those of the second-generation ferroptosis marker transferrin receptor (TfR), and restored the mRNA levels of the recently recognized cytosolic iron chaperone poly(RC) binding protein 2. In addition, hATf treatment lowered the ICH-induced increase in both endogenous mouse transferrin mRNA levels and the activation of caspase-2. In conclusion, hATf treatment provides neurobehavioral benefits post-ICH associated with the modulation of iron/oxidative players.