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El objetivo de este artículo es ahondar en la tesis de la inconmensurabilidad taxonómica defendida por Kuhn a partir de los años ochenta. Según el autor estadounidense, la inconmensurabilidad entre teorías, en esta versión más local y moderada, es el resultado del cambio semántico de algunos términos centrales, a los cuales denomina “categorías taxonómicas”. Según Kuhn, dichos términos están interdefinidos holísticamente, de manera que la modificación del significado de uno de ellos implica una redefinición del resto. Para extraer ejemplos de tal holismo local y de la reestructuración semántica que se produce tras una revolución científica, Kuhn acude a la física aristotélica y newtoniana. Sin embargo, aunque los considera ejemplos de gran relevancia y los utiliza como pruebas concluyentes de sus ideas, no los desarrolla en profundidad. Por lo tanto, este artículo se propone comprobar de manera más detallada si un análisis de tales teorías apoya la tesis de la inconmensurabilidad taxonómica.

Recently developed small-molecule inhibitors of the lysosomal protease dipeptidyl peptidase 1 (DPP1), also known as cathepsin C (CatC), can suppress suppurative inflammation in vivo by blocking the processing of zymogenic (pro-) forms of neutrophil serine proteases (NSPs), including neutrophil elastase, proteinase 3, and cathepsin G. DPP1 also plays an important role in activating granzyme serine proteases that are expressed by cytotoxic T lymphocytes (CTL) and natural killer (NK) cells. Therefore, it is critical to determine whether DPP1 inhibition can also cause off-target suppression of CTL/NK-cell-mediated killing of virus-infected or malignant cells. Herein, we demonstrate that the processing of human granzymes A and B, transitioning from zymogen to active proteases, is not solely dependent on DPP1. Thus, the killing of target cells by primary human CD8+ T cells, NK cells, and gene-engineered anti-CD19 CAR T cells was not blocked in vitro even after prior exposure to high concentrations of the reversible DPP1 inhibitor brensocatib. Consistent with this observation, the turnover of model granzyme A/B peptide substrates in the human CTL/NK cell lysates was not significantly reduced by brensocatib. In contrast, preincubation with brensocatib almost entirely abolished (>90%) both the cytotoxic activity of mouse CD8+ T cells and granzyme substrate turnover. Overall, our finding that the effects of DPP1 inhibition on human cytotoxic lymphocytes are attenuated in comparison to those of mice indicates that granzyme processing/activation pathways differ between mice and humans. Moreover, the in vitro data suggest that human subjects treated with reversible DPP1 inhibitors, such as brensocatib, are unlikely to experience any appreciable deficits in CTL/NK-cell-mediated immunities.

Objectives: Compromised hepatic fatty acid oxidation (FAO) has been observed in human MASH patients and animal models of MASLD/MASH. It remains poorly understood how and when the hepatic FAO pathway is suppressed during the progression of MASLD towards MASH. Hepatic ChREBP⍺ is a classical lipogenic transcription factor that responds to the intake of dietary sugars. Methods: We examined its role in regulating hepatocyte fatty acid oxidation (FAO) and the impact of hepatic Chrebpa deficiency on sensitivity to diet-induced MASLD/MASH in mice. Results: We discovered that hepatocyte ChREBP⍺ is both necessary and sufficient to maintain FAO in a cell-autonomous manner independently of its DNA-binding activity. Supplementation of synthetic PPAR⍺/δ agonist is sufficient to restore FAO in Chrebp−/− primary mouse hepatocytes. Hepatic ChREBP⍺ was decreased in mouse models of diet-induced MAFSLD/MASH and in patients with MASH. Hepatocyte-specific Chrebp⍺ knockout impaired FAO, aggravated liver steatosis and inflammation, leading to early-onset fibrosis in response to diet-induced MASH. Conversely, liver overexpression of ChREBP⍺-WT or its non-lipogenic mutant enhanced FAO, reduced lipid deposition, and alleviated liver injury, inflammation, and fibrosis. RNA-seq analysis identified the CYP450 epoxygenase (CYP2C50) pathway of arachidonic acid metabolism as a novel target of ChREBP⍺. Over-expression of CYP2C50 partially restores hepatic FAO in primary hepatocytes with Chrebp⍺ deficiency and attenuates preexisting MASH in the livers of hepatocyte-specific Chrebp⍺-deleted mice. Conclusions: Our findings support the protective role of hepatocyte ChREBPa against diet-induced MASLD/MASH in mouse models in part via promoting CYP2C50-driven FAO.

La experiencia narrada en este artículo intenta contribuir a una mayor inclusión educativa en instituciones de la ciudad de Santa Fe mediante la utilización de las Tecnologías de la Información y la Comunicación como herramientas útiles para el aprendizaje significativo de contenidos estructurantes de ciencias naturales en el nivel medio. Se trabaja junto al personal docente de instituciones socias del proyecto, que no disponen de materiales de laboratorio ni de una infraestructura edilicia adecuada, en el desarrollo de actividades experimentales simples mediadas por tecnologías digitales, que contribuyan a la enseñanza de temáticas relacionadas con la Química propuestas en el diseño curricular provincial. El trabajo sinérgico del equipo extensionista y del profesorado socio del proyecto facilitó la implementación de estrategias didácticas relevantes en contextos signados por la falta de recursos y en donde resulta dificultoso garantizar una educación de calidad para los y las estudiantes de sectores vulnerables.

Research question Is withholding anticoagulation for patients with isolated or incidental subsegmental pulmonary embolism clinically and cost-effective compared with full anticoagulation for 3 months? Background There has been an increase in the diagnosis of subsegmental pulmonary embolism since the advent of computed tomography pulmonary angiogram to investigate patients with suspected pulmonary embolism. Subsegmental pulmonary embolism is not often detectable with older nuclear medicine-based diagnostic imaging for ventilation/perfusion mismatch. The case fatality of pulmonary embolism has reduced as subsegmental pulmonary embolism diagnoses from computed tomography pulmonary angiogram have increased. There is growing equipoise about the optimal treatment for patients with subsegmental pulmonary embolism, given that full anticoagulation has significant risks of bleeding and subsegmental pulmonary embolism was not often diagnosed previously with ventilation/perfusion scanning and therefore most likely left predominantly untreated prior to the introduction of computed tomography pulmonary angiogram scanning. Objectives Determine whether withholding anticoagulation for isolated or incidental subsegmental pulmonary embolism (i.e. subsegmental pulmonary embolism with no coexisting deep-vein thrombosis) reduces the harms of recurrent thromboembolism and major bleeding compared with 3 months of full anticoagulation at 3, 6 and 12 months. Determine the rate of complications of anticoagulation therapy (predominantly bleeding) in patients with isolated subsegmental pulmonary embolism. Determine whether not treating isolated subsegmental pulmonary embolism is acceptable to clinicians and patients. Determine the reclassification rate of subsegmental pulmonary embolism diagnoses made by general reporting radiologists when reviewed by specialist respiratory radiologists and develop a set of rules to improve general radiologists’ diagnoses of subsegmental pulmonary embolism. Assess cost-effectiveness of not treating patients with isolated subsegmental pulmonary embolism with anticoagulation, taking a health service perspective. Methods Prospective individually randomised open controlled trial with blinded end-point committee assessment for outcomes, powered for non-inferiority for recurrent venous thromboembolism and for superiority for bleeding events. An internal pilot phase is included for feasibility and acceptability of no anticoagulation. We planned to recruit 1466 patients from at least 50 acute hospital sites. Allowing for a dropout rate of 15%, this would have given us 90% power to detect a reduction in major and clinically relevant non-major bleeding from 7.3% in the anticoagulation arm to 3% in the intervention arm. We were powered to determine that a strategy of no anticoagulation was non-inferior to anticoagulation with an upper margin of a 2.3% increase in recurrent venous thromboembolism from an expected rate of 2% in those who receive full anticoagulation. We also planned to undertake a study comparing acute reporting radiologists’ diagnoses of subsegmental pulmonary embolism from all computed tomography pulmonary angiograms with specialist respiratory radiologists. This would have allowed us to determine safety in the pilot study (i.e. patients with pulmonary embolism that was in fact larger than subsegmental would have been identified) and develop guidance for subsegmental pulmonary embolism diagnosis for general radiologists. Patients with lived experience of thrombosis contributed to all aspects of the trial design and were part of the Trial Management Group. Progress of study The STOPAPE trial was stopped prematurely due to a low recruitment rate in the wake of the COVID pandemic and prioritisation of recovery of the National Institute for Health and Care Research research portfolio. There are no outcome data available for this trial. Separate NIHR Library publications will detail the linked qualitative study examining the views of patients and clinicians around withholding anticoagulation for isolated subsegmental pulmonary embolism as well as presenting all collected data of recruited patients. Funding This article presents independent research funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme as award number NIHR128073. A plain language summary of this research article is available on the NIHR Journals Library Website https://doi.org/10.3310/HRCW7937. Plain language summary Pulmonary embolism is a potentially serious condition, whereby blood clots cause a blockage of the blood supply to the lungs. The diagnosis of pulmonary embolism is made with a scan of the lungs, by showing areas where blood cannot get through the vessels easily due to blood clots. The treatment of pulmonary embolism includes anticoagulant medication (‘blood thinners’) that is taken over months and includes warfarin, an injectable form of heparin and directly acting oral anticoagulants. These medications work by preventing new clots from forming while the body’s own mechanisms break down the clots. As the scanning technology for pulmonary embolism has become more sensitive, smaller clots are being diagnosed. However, small pulmonary embolisms may not cause any symptoms and may be found incidentally on scans performed for other reasons. In these situations, it is unclear whether treatment is required for the pulmonary embolism. These clots in smaller blood vessels away from the centre of the lungs (subsegmental pulmonary embolism) may be removed by the body’s own mechanisms for dissolving clots without needing medications. Anticoagulant medication can cause side effects in some patients such as bleeding. For the anticoagulant medication to be appropriate in these smaller pulmonary embolisms, the benefits from preventing future blood clots (pulmonary embolism and deep-vein thrombosis) would need to outweigh the potential risks from the medication side effects. The STOPAPE study aimed to answer this question by testing whether we can safely withhold anticoagulation from patients diagnosed with subsegmental pulmonary embolism. Although we aimed to enrol 1466 patients in the trial with half getting usual care of anticoagulation and half getting no anticoagulation, we could not recruit patients quickly enough to the trial and, as a result, we could not continue with the STOPAPE study. This study protocol is published to help future research teams that wish to answer this research question.

Desde los bombardeos de Hiroshima y Nagasaki en 1945, la proliferación nuclear ha sido un fenómeno cargado de controversia. Mientras que algunos le atribuyen un efecto pacificador, otros, más pesimistas, enfatizan su potencial catastrófico. El presente artículo se propone aportar luz al estudio de las dinámicas estratégicas que rodean este fenómeno a través de un desglose de sus componentes clave y de una exploración de las motivaciones que empujan a los Estados a obtener armas nucleares. Ya que se sostiene que la probabilidad de proliferar para un Estado está determinada en gran medida por la interacción estratégica con sus adversarios, se recurre a la Teoría de juegos, en particular a los modelos de “dilema del prisionero” y “caza del ciervo”, para discutir sobre las tendencias que pueden conducir hacia un escenario de proliferación extendida o bien hacia una desnuclearización coordinada.

Affective responses during stressful, high-stakes situations can play an important role in shaping performance. For example, feeling shaky and nervous at a job interview can undermine performance, whereas feeling excited during that same interview can optimize performance. Thus, affect regulation—the way people influence their affective responses—might play a key role in determining high-stakes outcomes. To test this idea, we adapted a synergistic mindsets intervention (SMI) (Yeager et al. 2022 Nature 607, 512–520 (doi:10.1038/s41586-022-04907-7)) to a high-stakes esports context. Our approach was motivated by the idea that (i) mindsets both about situations and one’s stress responses to situations can be shaped to help optimize stress responses, and (ii) challenge versus threat stress responses will be associated with improved outcomes. After a baseline performance task, we randomly assigned gamers (n = 300) either to SMI or a control condition in which they learned brain facts. After two weeks of daily gaming, gamers competed in a cash-prize tournament. We measured affective experiences before the matches and cardiovascular responses before and throughout the matches. Contrary to predictions, gamers did not experience negative affect (including feeling stressed), thus limiting the capacity for the intervention to regulate physiological responses and optimize performance. Compared with the control participants, synergistic mindsets participants did not show greater challenge responses or improved performance outcomes. Though our adaptation of Yeager et al.’s SMI did not optimize esports performance, our findings point to important considerations regarding the suitability of an intervention such as this to different performance contexts of varying degrees of stressfulness.

Abstract Rationale It is unclear how each individual asthma symptom is associated with asthma diagnosis or control. Objectives To assess the performance of individual asthma symptoms in the identification of patients with asthma and their association with asthma control. Methods In this cross‐sectional study, we assessed real‐world data using the MASK‐air® app. We compared the frequency of occurrence of five asthma symptoms (dyspnea, wheezing, chest tightness, fatigue and night symptoms, as assessed by the Control of Allergic Rhinitis and Asthma Test [CARAT] questionnaire) in patients with probable, possible or no current asthma. We calculated the sensitivity, specificity and predictive values of each symptom, and assessed the association between each symptom and asthma control (measured using the e‐DASTHMA score). Results were validated in a sample of patients with a physician‐established diagnosis of asthma. Measurement and Main Results We included 951 patients (2153 CARAT assessments), with 468 having probable asthma, 166 possible asthma and 317 no evidence of asthma. Wheezing displayed the highest specificity (90.5%) and positive predictive value (90.8%). In patients with probable asthma, dyspnea and chest tightness were more strongly associated with asthma control than other symptoms. Dyspnea was the symptom with the highest sensitivity (76.1%) and the one consistently associated with the control of asthma as assessed by e‐DASTHMA. Consistent results were observed when assessing patients with a physician‐made diagnosis of asthma. Conclusions Wheezing and chest tightness were the asthma symptoms with the highest specificity for asthma diagnosis, while dyspnea displayed the highest sensitivity and strongest association with asthma control.

Immune checkpoint inhibitors have become essential antineoplastic agents in medical oncology over the past decade. However, they are associated with potentially fatal multisystem abnormalities, with increasing concern in gastrointestinal tract and its associated organs. We present a patient with advanced renal cell carcinoma, who presented with acute liver failure after the first dose of combined immunotherapy with nivolumab and ipilimumab. A thorough evaluation for viral, metabolic, and autoimmune causes was unremarkable. He was managed with steroids and made significant improvement. To our knowledge, this is the first documented case of acute liver failure following ipilimumab and nivolumab.

Purpose: The purpose of this case report is to outline the management of a 41-year-old female with pathological myopia and type II choroidal neovascularization (CNV) diagnosed by optical coherence tomography angiography (OCT-A) angio-B mode. Observations: The early detection of CNV with OCT-A angio-B mode and treatment with intra-vitreous injections of Bevacizumab contributed to the amelioration of her vision to 20/20, a better visual acuity than she had prior to treatment. Conclusions and importance: This case report suggests that an OCT-A scan may reveal the initial formation of abnormal vasculature before pathological changes are evident in structural OCT, allowing for prompt treatment and resolution in patients with myopic CNV.

We evaluated the effects of solvents with different polarities—methylene chloride (MC), methanol (MT), and hexane (HE) on the extraction of compounds from Mexican red pitaya seed oil. The fatty acid composition and the structural, rheological, and thermal properties of the different extracts were characterized. The results indicated that the highest yield of extraction was generated for MC (26.96%), as well as the greatest amount of Mono and Polyunsaturated fatty acids, while the lowest yield was for MT (16.86%). The antioxidant activity was greater in the MT treatment due to extractable compounds from high polarity. The generated extracts contained unsaturated fatty acids, mostly oleic and linoleic acids, and saturated fatty acids such as palmitic acid. The lowest solidification temperature was −6.35 ℃ for MC due to its fatty acid composition, and the degradation temperature was around 240 ℃. The viscosity is a quality parameter; the highest level was generated for the MC treatment, which was significantly different from HE and MT. The composition of the extracts was analyzed using the FT-IR spectroscopy and showed the typical characteristic of absorption bands for triglycerides with high frequency in bands 2852 cm−1 and 2924 cm−1, which indicated that the samples were rich in unsaturated and polyunsaturated acids. These results suggested that pitaya seed oil is an excellent alternative source of essential fatty acids with potential physiological benefits.

Abstract Background People with opioid use disorder (OUD) are high-risk for short-term mortality and morbidity. Emergency department (ED) interventions can reduce those risks, but benefits wane without ongoing community follow-up. Objective To evaluate an ED-based intensive community outreach program. Methods At two urban EDs between October 2019 and March 2020, we enrolled patients with OUD not currently on opioid agonist therapy (OAT) in a prospective cohort study evaluating a one-year intensive community outreach program, which provided ongoing addictions care, housing resources, and community support. We surveyed patients at intake and at scheduled outreach encounters at one, two, six, and twelve months. Follow-up surveys assessed OAT uptake, addictions care engagement, housing status, quality of life scores, illicit opioid use, and outreach helpfulness. We used descriptive statistics for each period and conducted sensitivity and subgroup analyses to account for missing data. Results Of 84 baseline participants, 29% were female and 32% were housed, with a median age of 33. Sixty participants (71%) completed at least one follow-up survey. Survey completion rates were 37%, 38%, 39%, and 40% respectively at one, two, six, and twelve months. Participants had a median of three outreach encounters. Among respondents, OAT was 0% at enrolment and ranged from 38% to 56% at follow-up; addictions care engagement was 22% at enrolment and ranged from 65% to 81% during follow-up; and housing was 40% at enrolment and ranged from 48% to 59% during follow-up. Improvements from baseline to follow-up occurred for all time periods. OAT and engagement in care benefits were maintained in sensitivity and subgroup analyses. Respondents rated the outreach program as helpful at all time periods, Conclusion An ED-initiated intensive outreach program for patients with OUD not yet on OAT was associated with a persistent increase in OAT use and engagement in care, as well as housing.

Abstract Background Hyalomma marginatum and H. rufipes are two-host tick species, which are mainly distributed in southern Europe, Africa to central Asia but may also be found in Central and Northern Europe through introduction by migratory birds. Methods Ticks were collected while feeding or crawling on animals and humans, or from the environment, in different regions in Germany, between 2019 and 2021 in a citizen science study and from 2022 to 2023 in the wake of this study. Results From 2019 to 2023, a total of 212 Hyalomma adult ticks were detected in Germany. This included 132 H. marginatum and 43 H. rufipes ticks sent to research institutions and 37 photographic records that were only identified to genus level. The number of detected ticks varied over the years, with the highest number of 119 specimens recorded in 2019, followed by 57 in 2020. Most of the specimens were collected from horses, while some were collected from other animals, humans or found crawling on human clothes or other objects inside or outside houses. The screening of 175 specimens for Crimean-Congo hemorrhagic fever virus and of 132 specimens for Babesia/Theileria spp. by PCR gave negative results, while human-pathogenic Rickettsia were detected in 44% (77/175) of the total samples. Subsequent amplicon sequencing and phylogenetic analysis of representative samples determined the species of 41 Rickettsia aeschlimannii and one R. slovaca sequences. Conclusions Analysis of climatic factors indicated a significantly higher probability of Hyalomma occurrence at locations with higher average spring temperature during the years 2019 and 2020 compared to randomly generated pseudo-absence locations. Dry and hot conditions probably facilitated Hyalomma nymphs’ survival and molting into adults during these years. Graphical Abstract

Abstract Background To evaluate structural changes in retina and choroid in patients with type 2 diabetes (T2D) and their association with diabetic kidney disease (DKD). Methods T2D patients with mild or no diabetic retinopathy (DR) were followed for 3 years using structural SS-OCT and OCT angiography (OCT-A) taken every 6 months. Parameters were compared longitudinally and according to the DKD status on baseline. Results One hundred and sixty eyes from 80 patients were followed for 3 years, 72 with no DKD (nDKD) at baseline and 88 with DKD. Trend analysis of T2D showed significant thinning in GCL + and circumpapillary retinal fiber neural layer (cRFNL), choroid, and decreased vascular density (VD) in superficial plexus and central choriocapillaris with foveal avascular zone (FAZ) enlargement. Patients with no DKD on baseline presented more significant declines in retinal center and choroidal thickness, increased FAZ and loss of nasal and temporal choriocapillaris volume. In addition, the nDKD group had worse glycemic control and renal parameters at the end of the study. Conclusion Our data suggests the potential existence of early and progressive neurovascular damage in the retina and choroid of patients with Type 2 Diabetes (T2D) who have either no or mild Diabetic Retinopathy (DR). The progression of neurovascular damage appears to be correlated with parameters related to glycemic control and renal damage.

Abstract Background Hospital at Home (HaH) provides intensive, hospital-level care in patients’ homes for acute conditions that would normally require hospitalisation, using multidisciplinary teams. As a programme of complex medical-social interventions, a HaH programme theory has not been fully articulated although implicit in the structures, functions, and activities of the existing HaH services. We aimed to unearth the tacit theory from international evidence and test the soundness of it by studying UK HaH services. Methods We conducted a literature review (29 articles) adopting a ‘realist review’ approach (theory articulation) and examined 11 UK-based services by interviewing up to 3 staff members from each service (theory testing). The review and interview data were analysed using Framework Analysis and Purposive Text Analysis. Results The programme theory has three components- the organisational, utilisation and impact theories. The impact theory consists of key assumptions about the change processes brought about by HaH’s activities and functions, as detailed in the organisational and utilisation theories. HaH teams should encompass multiple disciplines to deliver comprehensive assessments and have skill sets for physically delivering hospital-level processes of care in the home. They should aim to treat a broad range of conditions in patients who are clinically complex and felt to be vulnerable to hospital acquired harms. Services should cover 7 days a week, have plans for 24/7 response and deliver relational continuity of care through consistent staffing. As a result, patients’ and carers’ knowledge, skills, and confidence in disease management and self-care should be strengthened with a sense of safety during HaH treatment, and carers better supported to fulfil their role with minimal added care burden. Conclusions There are organisational factors for HaH services and healthcare processes that contribute to better experience of care and outcomes for patients. HaH services should deliver care using hospital level processes through teams that have a focus on holistic and individually tailored care with continuity of therapeutic relationships between professionals and patients and carers resulting in less complexity and fragmentation of care. This analysis informs how HaH services can organise resources and design processes of care to optimise patient satisfaction and outcomes.

Abstract Background African ancestry populations have the highest burden of stroke worldwide, yet the genetic basis of stroke in these populations is obscure. The Stroke Investigative Research and Educational Network (SIREN) is a multicenter study involving 16 sites in West Africa. We conducted the first-ever genome-wide association study (GWAS) of stroke in indigenous Africans. Methods Cases were consecutively recruited consenting adults (aged > 18 years) with neuroimaging-confirmed ischemic stroke. Stroke-free controls were ascertained using a locally validated Questionnaire for Verifying Stroke-Free Status. DNA genotyping with the H3Africa array was performed, and following initial quality control, GWAS datasets were imputed into the NIH Trans-Omics for Precision Medicine (TOPMed) release2 from BioData Catalyst. Furthermore, we performed fine-mapping, trans-ethnic meta-analysis, and in silico functional characterization to identify likely causal variants with a functional interpretation. Results We observed genome-wide significant (P-value < 5.0E−8) SNPs associations near AADACL2 and miRNA (MIR5186) genes in chromosome 3 after adjusting for hypertension, diabetes, dyslipidemia, and cardiac status in the base model as covariates. SNPs near the miRNA (MIR4458) gene in chromosome 5 were also associated with stroke (P-value < 1.0E−6). The putative genes near AADACL2, MIR5186, and MIR4458 genes were protective and novel. SNPs associations with stroke in chromosome 2 were more than 77 kb from the closest gene LINC01854 and SNPs in chromosome 7 were more than 116 kb to the closest gene LINC01446 (P-value < 1.0E−6). In addition, we observed SNPs in genes STXBP5-AS1 (chromosome 6), GALTN9 (chromosome 12), FANCA (chromosome 16), and DLGAP1 (chromosome 18) (P-value < 1.0E−6). Both genomic regions near genes AADACL2 and MIR4458 remained significant following fine mapping. Conclusions Our findings identify potential roles of regulatory miRNA, intergenic non-coding DNA, and intronic non-coding RNA in the biology of ischemic stroke. These findings reveal new molecular targets that promise to help close the current gaps in accurate African ancestry-based genetic stroke’s risk prediction and development of new targeted interventions to prevent or treat stroke.

The new multimodal reading ecosystem currently contributes to the proposal of forms of mediation that take into account the hybridization of digital and analog paradigms. In this context, illustrated books intended for children can constitute an area of interest, since their discursive and aesthetic codes contribute to the development of multimodal reading strategies and to the positioning of the child reader before the information, at the same time that they generate pleasant reading and knowledge-building experiences. Accordingly, today’s publishing market requires a learning process from the mediator in order to develop the corresponding strategies with which to approach children’s books. Previous research has focused on the book trailer as a virtual epitext for the promotion of publications, and it has analyzed the identity of this tool to demonstrate its effectiveness in the promotion of reading. Along these lines, and with the purpose of verifying how this tool behaves in the introduction of future teachers to children’s books, an intervention is proposed that is based on the creation of book trailers. A total of 860 students from the Early Childhood and Primary Education teaching degree programs participated in the intervention. It included qualitative research that analyzed the documents/epitexts created by the students, written reflections within the framework of this project and the discourse collected a posteriori in interviews and discussion groups on the experience. The results reveal the potential that creating book trailers has for introducing teacher trainees to illustrated children’s books within the framework of the digital society.

Abstract Circulating tumour DNA (ctDNA) detection via liquid biopsy is an emerging alternative to tissue biopsy, but its potential in treatment response monitoring and prognosis in triple negative breast cancer (TNBC) is not yet well understood. Here we determined the prevalence of actionable mutations detectable in ctDNA using a clinically validated cancer gene panel assay in patients with TNBC, without recurrence at the time of study entry. Sequencing of plasma DNA and validation of variants from 130 TNBC patients collected within 7 months of primary treatment completion revealed that 7.7% had detectable residual disease with a hotspot panel. Among neoadjuvant treated patients, we observed a trend where patients with incomplete pathologic response and positive ctDNA within 7 months of treatment completion were at much higher risk of reduced progression free survival. We propose that a high risk subset of early TNBC patients treated in neoadjuvant therapy protocols may be identifiable by combining tissue response and sensitive ctDNA detection.

Purpose: Men are increasingly turning toward online direct-to-consumer (DTC) men’s health platforms to fulfill their health needs. Research surrounding these platforms is lacking and the motivations and predictors underlying this online healthseeking behavior is largely unknown. This review scopes the existing literature concerning DTC men’s health and identifies factors influencing engagement, as well as health outcomes of this platform. Materials and Methods: A structured search was performed following PRISMA guidelines. CINAHL via EBSCO, Embase, MEDLINE via Ovid, PsycINFO, PubMed and Web of Science were searched. Results: Peer-reviewed quantitative and qualitative studies with a focus on demographics and characteristics of those using DTC men’s health platforms, as well as studies related to patient outcomes using such platforms, were included. Ten of the 3,003 studies identified met the inclusion and exclusion criteria. Four cross-sectional descriptive studies evaluated the motivations behind men’s engagement with DTC platforms. Convenience, embarrassment and health motivation were identified as predominant factors associated with DTC platform use. The review identified a lack of qualitative studies, and major limitations were noted in the quantitative studies that impacted the accuracy of findings. Six further quantitative studies explored the quality of care provided by DTC platforms. DTC platforms were found to have a varying level of adherence to established clinical guidelines, but appeared to provide satisfactory patient outcomes with low levels of patient-reported side effects and adverse events. Conclusions: There is a lack of research within the DTC men’s health space given the infancy of the field. Important predictors and motivations underlying men’s choices in accessing these platforms have been noted across several studies. However, further studies need to be conducted to investigate the psychosocial underpinnings of this behavior. Studies across a wider variety of male health conditions treated by these platforms will also help to provide insights to guide patient-centered care within the DTC landscape.

Abstract Background The need to improve the acute care pathway to meet the care needs of older people living with frailty is a strategic priority for many healthcare systems. The optimal care model for this patient group is unclear. Methods A systematic review was conducted to derive a taxonomy of acute care models for older people with acute medical illness and describe the outcomes used to assess their effectiveness. Care models providing time-limited episodes of care (up to 14 days) within 48 h of presentation to patients over the age of 65 with acute medical illness were included. Care models based in hospital and community settings were eligible. Searches were undertaken in Medline, Embase, CINAHL and Cochrane databases. Interventions were described and classified in detail using a modified version of the TIDIeR checklist for complex interventions. Outcomes were described and classified using the Core Outcome Measures in Effectiveness Trials (COMET) taxonomy. Risk of bias was assessed using RoB2 and ROBINS-I. Results The inclusion criteria were met by 103 articles. Four classes of acute care model were identified, acute-bed based care, hospital at home, emergency department in-reach and care home models. The field is dominated by small single centre randomised and non-randomised studies. Most studies were judged to be at risk of bias. A range of outcome measures were reported with little consistency between studies. Evidence of effectiveness was limited. Conclusion Acute care models for older people living with frailty are heterogenous. The clinical effectiveness of these models cannot be conclusively established from the available evidence. Trial registration PROSPERO registration (CRD42021279131).

This study examines the experiences of lesbian-parent families in Chile regarding the civil registry and the registration of their children, highlighting how heteronormative structures persist despite significant legislative advancements. Through semi-structured interviews with lesbian mothers, it explored how the policies and practices occurring at the civil registry affect their rights and legal recognition. The qualitative data analysis revealed significant barriers in the filiation processes due to outdated forms and lack of training among officials, reflecting a disconnect between progressive legislation and its practical implementation. The findings indicate that while there is growing social recognition of family diversity, lesbian-parent families face institutional discrimination, limiting their full participation in society. These barriers not only perpetuate occupational injustices but also negatively affect the emotional and social well-being of these families. This study underscores the need for legislative and administrative reforms to ensure effective inclusion and recognition of lesbian-parent families, recommending policies that update administrative processes to reflect the realities of all families adequately. The research highlights the importance of continuous education and awareness for civil registry workers, ensuring that existing laws are applied fairly and equitably.

Background and Objectives: Hypertensive disorders, particularly pre-eclampsia, pose significant risks during pregnancy, affecting both maternal and neonatal health. The study aims to analyze short- and long-term health implications for mothers and their children, comparing those with pre-eclampsia to those without, to improve understanding of risk factors, diagnostic markers, and outcomes. Materials and Methods: This retrospective observational study involved 235 patients, 98 with pre-eclampsia and 137 without, monitored from 2015 to 2018 at the Obstetrics and Gynecology Department of the “Pius Brînzeu” Emergency County Clinical Hospital in Timișoara, Romania. Results: Women with pre-eclampsia were older, had higher BMIs, and more frequently had a family history of pre-eclampsia, hypertension, and diabetes. They also had lower educational and socioeconomic levels and fewer prenatal visits. Biochemical markers such as higher proteinuria, elevated sFlt-1, and lower PlGF were significant in diagnosing pre-eclampsia. Short-term maternal complications like eclampsia, HELLP syndrome, and acute kidney injury were more prevalent in the pre-eclampsia group. Neonatal outcomes included higher rates of preterm birth, low birth weight, and NICU admissions. Long-term mothers with a history of pre-eclampsia had higher incidences of chronic hypertension, cardiovascular disease, kidney problems, diabetes, and mental health disorders. Their children faced increased risks of neuropsychological delays, chronic respiratory issues, behavioral disorders, learning difficulties, and frequent infections. Conclusions: The study highlights the significant short- and long-term health impacts of pre-eclampsia on both mothers and their children. Early monitoring, intervention, and comprehensive management are crucial in mitigating these risks. These findings underscore the need for personalized care strategies to improve health outcomes for affected individuals.

The use of a pretrained image classification model (trained on cats and dogs, for example) as a perceptual loss function for hyperspectral super-resolution and pansharpening tasks is surprisingly effective. However, RGB-based networks do not take full advantage of the spectral information in hyperspectral data. This inspired the creation of HyperKon, a dedicated hyperspectral Convolutional Neural Network backbone built with self-supervised contrastive representation learning. HyperKon uniquely leverages the high spectral continuity, range, and resolution of hyperspectral data through a spectral attention mechanism. We also perform a thorough ablation study on different kinds of layers, showing their performance in understanding hyperspectral layers. Notably, HyperKon achieves a remarkable 98% Top-1 retrieval accuracy and surpasses traditional RGB-trained backbones in both pansharpening and image classification tasks. These results highlight the potential of hyperspectral-native backbones and herald a paradigm shift in hyperspectral image analysis.

The present work reports a comparative study on CuO and 3.0% Mn-doped CuO nanofibers (NFs) produced by the electrospinning method. State-of-the-art characterization techniques such as Electron Energy Loss Spectroscopy (EELS) and X-Ray photoelectron Spectroscopy (XPS) have been employed to determine the multivalent states and elucidate their electronic structure at the Cu-L3,2 (2p) edge. The CASTEP code has been used to model CuO (P1) and Mn-doped (C 2/c) with the GGA-PBE functional on the supercomputing system with the Xeon10 module (10 nuclei). Structural characterization was done by using a CM 200 Philips Transmission Electron Microscope (TEM) and the chemical state of surfaces with ESCALAB 250Xi XPS Thermoscientific TM. The NFs present an indirect energy bandgap, Eg = 2.03 eV and 2.85 eV, respectively. The results show that the Cu-L3,2 edge presents degenerate states associated with Cu 2p - O and Cu 3d - O hybridization, indicated as Cu3+.

Abstract Background An innovation to better manage cat‐allergic patients utilises anti‐Fel d 1 IgY antibodies to neutralise Fel d 1 after its production by the cat. However, there is no published study showing its clinical efficacy in humans in a home setting. A longitudinal, open‐label, proof‐of‐concept study was carried out to approach clinical efficacy of the cat food in cat‐allergic patients. Methods After a baseline evaluation, the cats ate only the cat food for the following 4 months. Daily evaluation of efficacy was performed for 2 weeks at baseline and after 1, 2 and 3 months of intervention for periods of 2 weeks. The MASK‐air app was used daily to assess symptoms, work productivity and medications. Results Of the 49 patients screened, 42 were followed up and 33 (78.5%) reported MASK‐air data at all 3 evaluation periods. The primary end point (visual analogue scale [VAS] for global allergy symptoms) was significantly improved (p 20/100) decreased from 64% at baseline to 35% at 1 month (p

Abstract Male lobsters (Homarus americanus) harvested as ‘quarters’ (1.25 lbs/567 g) in two time periods (winter, N = 16, and summer, N = 25) of 2018 are examined. Indicators of quality data were collected for each lobster, including non‐invasive measures (shell hardness, carapace length, sex, live weight, colour, body shape, location, time of harvest) and invasive measures (blood protein [BRIX] level at time of harvest, cooked weight, meat content). Lobster BRIX levels are used as a proxy for actual meat content and as the key indicator of lobster quality. A regression model of the relationship between the natural logarithmic transformation of lobster BRIX levels (independent variable) and meat content yield as a percentage of shell‐on (uncooked) weight (dependent variable) is presented. The objective of this study is to evaluate alternative BRIX‐based decision rules for achieving desired meat content percentage yields for preparing shipments to global markets. The present study found that BRIX‐based grading rules can be determined to achieve minimum desired meat yields, minimum overall shipment yields and minimum proportions of shipments below desirable yield rate. For a minimum desired industry threshold of 24% meat content, the preferred BRIX value rules are (i) 8.5 mg mL−1 and (ii) ‘9 mg mL−1 with 10% plus condition’. These rules improve the admissibility of samples and reduce the risk of below desirable meat yields.

Introduction Whole blood (WB) transfusion represents a promising resuscitation strategy for trauma patients. However, a paucity of data surrounding the optimal incorporation of WB into resuscitation strategies persists. We hypothesized that traumatically injured patients who received a greater proportion of WB compared with blood product components during their resuscitative efforts would have improved early mortality outcomes and decreased transfusion requirements compared with those who received a greater proportion of blood product components.Methods Retrospective review from our Level 1 trauma center of trauma patients during their initial resuscitation (2019–2022) was performed. WB to packed red blood cell ratios (WB:RBC) were assigned to patients based on their respective blood product resuscitation at 1, 2, 3, and 24 hours from presentation. Multivariable regression models were constructed to assess the relationship of WB:RBC to 4 and 24-hour mortality, and 24-hour transfusion requirements.Results 390 patients were evaluated (79% male, median age of 33 years old, 48% penetrating injury rate, and a median Injury Severity Score of 27). Overall mortality at 4 hours was 9%, while 24-hour mortality was 12%. A significantly decreased 4-hour mortality was demonstrated in patients who displayed a WB:RBC≥1 at 1 hour (5.9% vs. 12.3%; OR 0.17, p=0.015), 2 hours (5.5% vs. 13%; OR 0.16, p=0.019), and 3 hours (5.5% vs. 13%, OR 0.18, p

Abstract The polymer transition temperature is a crucial parameter in the industry for knowing raw materials before starting the manufacturing process. The current work reports a novel low-cost prototype instrument to measure the transition temperature with reliable accuracy. The equipment was built using commercial load cells composed of strain gauges in combination with an Arduino® microcontroller. The prototype measurement quality was validated by measuring the transition temperatures of most commercial polymers. The obtained values were compared with values obtained by conventional thermal analysis known as differential scanning calorimetric and thermo-mechanical analysis (DSC and TMA), which results in identical values.

In Markov chain theory, performance parameters are indicator of the proper management of a queue. In this field, an abundant literature exists, particularly in the steady state, which is not the case in the transient state. It is in this context that we can question whether it is possible to establish the equations of the performance measures in the transient regime with absolute priority given the complexity of the study of Markov chains in a transient regime. To achieve this, we used the analytical method based on the exploitation of the Laplace transform in the Kolmogorov equations, as well as the theory of convergent series in the equations resulting from the transition matrices. This analysis is supported by the descriptive technique. These tools allowed us to produce concrete results; which are the performance measures of priority and no priority customers in a transient regime M/M/1 queue. Which is a plus in the field of Markov chains. The purpose of this paper is to analyse the M/M/1 transient performance measures with absolute priority. Its originality lies in the fact that we have determined the expressions of the performance measures of non-priority customers in a transient regime. Indeed, very few publications are made in this area at this time. A numerical application was treated to illustrate the theory evoked above. This reflection could soon be carried out in a fuzzy environment.

IntroductionNowadays, more and more digital resources are used in modern mathematical modeling classes. In order to access these resources, students need a suitable digital device—often mobile devices are used for this purpose. There are several concepts to enable students access to such devices. For example, students can be allowed to use their self-owned devices [Bring Your Own Device (BYOD) concept] or teachers can hand out school-owned devices to their students [device pool (pool) concept]. Currently, little is known about possible effects of different mobile device access concepts on student learning. Hence, in this study, we investigated their effects on students’ mathematical modeling competence. In doing so, we also considered an interaction between the access concept and the effects of (a) students’ problematic smartphone use and (b) students’ fear of missing out on learning mathematical modeling.MethodTo this end, we conducted an experiment, measured students’ mathematical modeling competence as the outcome variable, and analyzed data of 263 German students in grades 8 and 9 using a multilevel model. In the experiment, students were randomly assigned to one of two study conditions and completed a mathematics modeling workshop. In the BYOD condition, students utilized their self-owned smartphones to work on the workshop tasks, whereas in the pool condition, students utilized institutionally provided smartphones.ResultsAs a main finding, our results showed an interaction effect between the mobile device access concept and students’ problematic smartphone use on their competence (β = −0.24, 95% CI [−0.47, −0.01]). Students utilizing their self-owned smartphones were negatively affected by their problematic smartphone use (B = −1.45, 95% CI [−2.45, −0.46]), whereas students utilizing provided smartphones were not affected (B = 0.04, 95% CI [−1.01, 1.09]). Students with maximal problematic smartphone use achieved higher competences when utilizing provided devices (BBYOD−Pool = −1.20, 95% CI [–2.35, –0.05]).DiscussionOur study demonstrates the importance of thinking about effects of student-owned and provided digital devices on mathematics learning. Finally, we discuss (a) that our results do not reveal a general preferability for one of the two access concepts, as well as (b) the relevance of student characteristics when choosing an access concept.

Vaccinating patients receiving dialysis may prevent morbidity and mortality in this vulnerable population. The National Forum of End-Stage Renal Disease Networks (the Forum) published a revised vaccination toolkit in 2021 to update evidence and recommendations on vaccination for patients receiving dialysis. Significant changes in the last 10 years include more data supporting the use of a high-dose influenza vaccine, the introduction of the Heplisav-B vaccine for hepatitis B, and changes in pneumococcal vaccines, including the approval of the PCV15 and PCV20 to replace the PCV13 and PPSV23 vaccines. Additional key items include the introduction of vaccines against severe acute respiratory syndrome coronavirus 2, the virus that causes coronavirus disease 2019 (COVID-19), and a new vaccine to prevent respiratory syncytial virus disease. Historically, influenza and pneumococcal vaccinations were routinely administered by dialysis facilities, and because of possible risks of hematogenous spread of hepatitis B, dialysis providers often have detailed hepatitis B vaccine protocols. In March 2021, COVID-19 vaccines were made available for dialysis facilities to administer, although with the end of the public health emergency, vaccine policies by dialysis facilities against COVID-19 remains uncertain. The respiratory syncytial virus vaccine was authorized in 2023, and how dialysis facilities will approach this vaccine also remains uncertain. This review summarizes the Forum’s vaccination toolkit and discusses the role of the dialysis facility in vaccinating patients to reduce the risk of severe infections.

Abstract Background The gut microbiome is a salient contributor to the development of obesity, and diet is the greatest modifier of the gut microbiome, which highlights the need to better understand how specific diets alter the gut microbiota to impact metabolic disease. Increased dietary fiber intake shifts the gut microbiome and improves energy and glucose homeostasis. Dietary fibers are found in various plant-based flours which vary in fiber composition. However, the comparative efficacy of specific plant-based flours to improve energy homeostasis and the mechanism by which this occurs is not well characterized. Methods In experiment 1, obese rats were fed a high fat diet (HFD) supplemented with four different plant-based flours for 12 weeks. Barley flour (BF), oat bran (OB), wheat bran (WB), and Hi-maize amylose (HMA) were incorporated into the HFD at 5% or 10% total fiber content and were compared to a HFD control. For experiment 2, lean, chow-fed rats were switched to HFD supplemented with 10% WB or BF to determine the preventative efficacy of flour supplementation. Results In experiment 1, 10% BF and 10% WB reduced body weight and adiposity gain and increased cecal butyrate. Gut microbiota analysis of WB and BF treated rats revealed increases in relative abundance of SCFA-producing bacteria. 10% WB and BF were also efficacious in preventing HFD-induced obesity; 10% WB and BF decreased body weight and adiposity, improved glucose tolerance, and reduced inflammatory markers and lipogenic enzyme expression in liver and adipose tissue. These effects were accompanied by alterations in the gut microbiota including increased relative abundance of Lactobacillus and LachnospiraceaeUCG001, along with increased portal taurodeoxycholic acid (TDCA) in 10% WB and BF rats compared to HFD rats. Conclusions Therapeutic and preventative supplementation with 10%, but not 5%, WB or BF improves metabolic homeostasis, which is possibly due to gut microbiome-induced alterations. Specifically, these effects are proposed to be due to increased concentrations of intestinal butyrate and circulating TDCA.

Abstract The psoriatic skin resembles wound healing, and it shows abnormalities at the basement membrane (BM), also in the non-lesional skin. Fibroblast-derived dermal periostin has well-known functions in wound healing and Th2-mediated diseases, such as atopic dermatitis. Here we show that serum periostin level was elevated in psoriatic patients, remarkably in the systemically treated ones. Obvious periostin positivity was detected in basal keratinocytes of the non-lesional, lesional, and previously-lesional psoriatic vs. healthy skin. Ex vivo skin models were generated to examine how different skin injuries affect periostin expression during wound healing. Our newly developed cultured salt-split model demonstrated that BM-injury induced periostin expression in basal keratinocytes, and periostin levels in the supernatant were also increased upon healing. In wound healing models, β1-integrin expression was similarly induced. β1-integrin blocking caused reduced periostin expression in in vitro scratch assay, indicating that β1-integrin can mediate periostin production. In contrast to atopic dermatitis, psoriatic basal keratinocytes are in an activated state and show a stable wound healing-like phenotype with the overexpression of periostin. This abnormal BM-induced wound healing as a potential compensatory mechanism can be initiated already in the non-lesional skin present in the lesion and keratinocytes can remain activated in the healed skin.

Abstract Background Fraud, Waste, and Abuse (FWA) in medical claims have a negative impact on the quality and cost of healthcare. A major component of FWA in claims is procedure code overutilization, where one or more prescribed procedures may not be relevant to a given diagnosis and patient profile, resulting in unnecessary and unwarranted treatments and medical payments. This study aims to identify such unwarranted procedures from millions of healthcare claims. In the absence of labeled examples of unwarranted procedures, the study focused on the application of unsupervised machine learning techniques. Methods Experiments were conducted with deep autoencoders to find claims containing anomalous procedure codes indicative of FWA, and were compared against a baseline density-based clustering model. Diagnoses, procedures, and demographic data associated with healthcare claims were used as features for the models. A dataset of one hundred thousand claims sampled from a larger claims database is used to initially train and tune the models, followed by experimentations on a dataset with thirty-three million claims. Experimental results show that the autoencoder model, when trained with a novel feature-weighted loss function, outperforms the density-based clustering approach in finding potential outlier procedure codes. Results Given the unsupervised nature of our experiments, model performance was evaluated using a synthetic outlier test dataset, and a manually annotated outlier test dataset. Precision, recall and F1-scores on the synthetic outlier test dataset for the autoencoder model trained on one hundred thousand claims were 0.87, 1.0 and 0.93, respectively, while the results for these metrics on the manually annotated outlier test dataset were 0.36, 0.86 and 0.51, respectively. The model performance on the manually annotated outlier test dataset improved further when trained on the larger thirty-three million claims dataset with precision, recall and F1-scores of 0.48, 0.90 and 0.63, respectively. Conclusions This study demonstrates the feasibility of leveraging unsupervised, deep-learning methods to identify potential procedure overutilization from healthcare claims.