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The images of the future among young people have been conditioned by the stories present in the media, films, books, and also in school. Educational curriculums are made up of a selection of knowledge that privileges some ways of understanding the future over others. Young people often imagine a future that is in economic, social, and/or climate crisis. However, they also imagine a bright future for themselves, detached from the future they imagine for society. In this article, we present a qualitative analysis of the curriculums of Australia, Spain, and Chile, together with interviews with teachers from these countries. We investigate the presence and absence of futures education in these curriculums, their degree of development regarding futures education, and make a first analysis of the influence of futures education in schools. To do this we identify four dimensions: situate in time, anticipate, imagine alternative futures, and social action. The results show that, while the Australian curriculum explicitly includes education for the future, the Spanish and Chilean curriculum include it only tangentially. In addition, the socio-cultural context of schools and the will of the teaching staff are elements that determine the implementation of futures education in the school context.

Despite increasing attention to citizenship education since the turn of the 21st century, the recent spread of authoritarian populism worldwide has raised relatively little attention in educational policy and research. As a result, the possibilities and limitations that national curricula offer to educators to deal with this phenomenon are still rather uncertain. In this article, we develop an analytical framework based on the key features of authoritarian populism and critical citizenship education to compare the elements and scope for addressing populism in the national curricula of Brazil and Spain, two countries where national populism is particularly widespread. This paper examines the extent to which national curricula in these countries include goals and content that enable teachers to address the complexities of this phenomenon ranging from political polarisation through to the exaltation of national identities.

Abstract Objective To assess the real-world, long-term effectiveness of rituximab (RTX) as a rescue therapy in patients with antisynthetase syndrome and progressive interstitial lung disease (ASS-ILD). Methods Multicentre observational retrospective longitudinal study of a cohort of patients with ASS-ILD that started treatment with RTX due to recurrent or ongoing progressive ILD despite therapy with glucocorticoids and immunosuppressants. Results Twenty-eight patients were analyzed. Examining the entire study population, before treatment with RTX the mean decline in %pFVC and %pDLCO from the ASS-ILD diagnosis to the initiation of RTX treatment (T0) was -6.44% and -14.85%, respectively. After six months of treatment, RTX reversed the decline in pulmonary function test (PFT) parameters: ∆%pFVC +6.29% (95% CI: -10.07 to 2.51; p=0.002 compared to T0) and ∆%pDLCO +6.15% (95% CI: -10.86 to -1.43; p=0.013). Twenty-four patients completed one year of therapy and 22 two years, maintaining the response in PFT: ∆%pFVC: +9.93% (95% CI: -15.61 to -4.25; p=0.002) and ∆%pDLCO: +7.66% (95% CI: -11.67 to -3.65; p

IntroductionSchool offers a key context to promote resilience. The aim of this study was to assess the effectiveness of a school-based resilience intervention in 578 at-risk adolescents aged 12 to 15, emphasizing the significance of resilience improving mental health.MethodsA cluster-randomized controlled trial with parallel arms was conducted during the 2021/22 academic course. A specific training of six 55-minute sessions over 6 weeks was carried out for the students. Each session consisted of 5 minutes of mindfulness, followed by 45 minutes of the corresponding activity: introduction to resilience, self-esteem, emotional regulation strategies, social skills, problem solving, community resources, and peer support. Primary outcomes were assessed by the Child Youth Resilience Measure-32 at baseline (T1), post-intervention (T2), and then at the 24-week follow-up (T3). Both groups were compared using the Student’s t-test. The effect size was calculated using Cohen’s d and linear regression models were used.ResultsA total of 578 adolescents were included, 323 in the control group and 255 in the intervention group. Significant differences in both crude and adjusted analyses for Child Youth Resilience Measure were observed at 24 weeks follow-up, showing higher resilience for the intervention group [IG, M = 128.7, SD = 14.2; CG, M = 125.3, SD = 18.4; p = 0.027; d = 0.2; p = 0.043, d = 0.16]. Furthermore, in Depressive symptoms, lower values were found for the intervention group in both crude and adjusted analyses [IG, M = 2.3 (SD = 2.5); CG, M = 2.8 (SD = 2.5); p = 0.04; d = −0.20; p = 0.037, d = −0.18].DiscussionThis study contributes to fostering resilience and positive adolescent development. It also reinforces the potential of multicomponent interventions. More continuous follow-up assessments are needed to identify possible long-term changes in resilience.Clinical Trial RegistrationIdentifier: NCT05133115. https://clinicaltrials.gov/study/NCT05133115.

Abstract Genome-wide association studies (GWAS) have identified more than 200 common genetic variants independently associated with colorectal cancer (CRC) risk, but the causal variants and target genes are mostly unknown. We sought to fine-map all known CRC risk loci using GWAS data from 100,204 cases and 154,587 controls of East Asian and European ancestry. Our stepwise conditional analyses revealed 238 independent association signals of CRC risk, each with a set of credible causal variants (CCVs), of which 28 signals had a single CCV. Our cis-eQTL/mQTL and colocalization analyses using colorectal tissue-specific transcriptome and methylome data separately from 1299 and 321 individuals, along with functional genomic investigation, uncovered 136 putative CRC susceptibility genes, including 56 genes not previously reported. Analyses of single-cell RNA-seq data from colorectal tissues revealed 17 putative CRC susceptibility genes with distinct expression patterns in specific cell types. Analyses of whole exome sequencing data provided additional support for several target genes identified in this study as CRC susceptibility genes. Enrichment analyses of the 136 genes uncover pathways not previously linked to CRC risk. Our study substantially expanded association signals for CRC and provided additional insight into the biological mechanisms underlying CRC development.

ObjectivesEarly- and late-onset Alzheimer's disease (EOAD and LOAD) share the same neuropathological traits but show distinct cognitive features. We aimed to explore baseline and longitudinal outcomes of global and domain-specific cognitive function in a well characterized cohort of patients with a biomarker-based diagnosis.MethodsIn this retrospective cohort study, 195 participants were included and classified according to their age, clinical status, and CSF AD biomarker profile: 89 EOAD, 37 LOAD, 46 young healthy controls (age ≤ 65 years), and 23 old healthy controls (>65 years). All subjects underwent clinical and neuropsychological assessment, neuroimaging, APOE genotyping and lumbar puncture.ResultsWe found distinct neuropsychological profiles between EOAD and LOAD at the time of diagnosis. Both groups showed similar performances on memory and language domains, but the EOAD patients displayed worsened deficits in visual perception, praxis, and executive tasks (p

Objective To assess the predictive value of four cardiovascular (CV) risk algorithms for identifying high-risk psoriatic arthritis (PsA) patients.Methods Evaluation of patients with PsA enrolled in the Spanish prospective project CARdiovascular in RheuMAtology. Baseline data of 669 PsA patients with no history of CV events at the baseline visit, who were followed in rheumatology outpatient clinics at tertiary centres for 7.5 years, were retrospectively analysed to test the performance of the Systematic Coronary Risk Assessment (SCORE), the modified version (mSCORE) European Alliance of Rheumatology Associations (EULAR) 2015/2016, the SCORE2 algorithm (the updated and improved version of SCORE) and the QRESEARCH risk estimator version 3 (QRISK3).Results Over 4790 years of follow-up, there were 34 CV events, resulting in a linearised rate of 7.10 per 1000 person-years (95% CI 4.92 to 9.92). The four CV risk scales showed strong correlations and all showed significant associations with CV events (p

The present study addresses the issue of the transfer from second language acquisition (SLA) research to second and foreign language (L2) instruction, particularly within the context of Task-Based Language Teaching (TBLT). The main goal of this article is to show how technology, particularly the web-based tool taskGen (https://taskgen.eu), which primarily serves to create teaching materials, also functions as a mediator for transfer and provides valuable information on teaching practices, teachers' needs, pedagogical strategies, and L2 task design. This article is organised as follows. Firstly, a web-based tool that assists and trains teachers in L2 task design is presented, along with the instantiation and integration of natural language processing (NLP) resources in the tool; later, we show how quantitative information obtained from the massive use of the tool through data analytics can be combined with qualitative methods such as interviews, observations, think aloud protocols, questionnaires, case studies, and transcripts to generate research. Automatic (quantitative) data collection gathers information of the teaching contexts, task aims, task flow structures, focus on form options, and the access and time on help files. Not only does the collected information feed back to the tool, but it also contributes to understanding teachers' design choices and patterns, and to exploring the intersection between SLA and TBLT theory and task design practises. Qualitative analysis is being conducted and oriented toward teachers’ experiences during task design. Finally, we present the future lines of research that we anticipate will be carried out with the further use and development of taskGen.

Abstract Polygenic risk scores (PRS) have great potential to guide precision colorectal cancer (CRC) prevention by identifying those at higher risk to undertake targeted screening. However, current PRS using European ancestry data have sub-optimal performance in non-European ancestry populations, limiting their utility among these populations. Towards addressing this deficiency, we expand PRS development for CRC by incorporating Asian ancestry data (21,731 cases; 47,444 controls) into European ancestry training datasets (78,473 cases; 107,143 controls). The AUC estimates (95% CI) of PRS are 0.63(0.62-0.64), 0.59(0.57-0.61), 0.62(0.60-0.63), and 0.65(0.63-0.66) in independent datasets including 1681-3651 cases and 8696-115,105 controls of Asian, Black/African American, Latinx/Hispanic, and non-Hispanic White, respectively. They are significantly better than the European-centric PRS in all four major US racial and ethnic groups (p-values

Aunque el rol de las mujeres en las festividades tradicionales en Cataluña ha sido subordinado al de los hombres, desde hace unos años las mujeres intentan ganar protagonismo. En este artículo se expone un estudio de caso realizado a propósito de un grupo de diablesas de la ciudad de Mataró (Barcelona). A partir de las entrevistas realizadas y un proceso de observación participante, se estudian las implicaciones que conlleva el hecho de romper con la hegemonía masculina con un grupo formado exclusivamente por mujeres, especialmente cuando se trata de una actividad festiva tradicionalmente ejercida por hombres. El texto analiza las dinámicas internas del grupo, su exposición pública y las relaciones entre poder y vulnerabilidad que conlleva su actividad. Finalmente, se discuten las paradojas que se producen entre un feminismo invisible o implícito y las relaciones de dominación masculina en el campo de la cultura tradicional y en el espacio público.

Objective This study aimed to estimate the incidence of giant cell arteritis (GCA) in Spain and to analyse its clinical manifestations, and distribution by age group, sex, geographical area and season.Methods We included all patients diagnosed with GCA between 1 June 2013 and 29 March 2019 at 26 hospitals of the National Health System. They had to be aged ≥50 years and have at least one positive results in an objective diagnostic test (biopsy or imaging techniques), meet 3/5 of the 1990 American College of Rheumatology classification criteria or have a clinical diagnosis based on the expert opinion of the physician in charge. We calculated incidence rate using Poisson regression and assessed the influence of age, sex, geographical area and season.Results We identified 1675 cases of GCA with a mean age at diagnosis of 76.9±8.3 years. The annual incidence was estimated at 7.42 (95% CI 6.57 to 8.27) cases of GCA per 100 000 people ≥50 years with a peak for patients aged 80–84 years (23.06 (95% CI 20.89 to 25.4)). The incidence was greater in women (10.06 (95% CI 8.7 to 11.5)) than in men (4.83 (95% CI 3.8 to 5.9)). No significant differences were found between geographical distribution and incidence throughout the year (p=0.125). The phenotypes at diagnosis were cranial in 1091 patients, extracranial in 337 patients and mixed in 170 patients.Conclusions This is the first study to estimate the incidence of GCA in Spain at a national level. We found a predominance among women and during the ninth decade of life with no clear variability according to geographical area or seasons of the year.

IntroductionThis was an ambispective cohort study evaluating the prognostic significance of lymphocytic foci and its lymphoid composition in minor salivary gland biopsy (MSGB) for short-term disease flare and severity in Sjögren’s syndrome (SS).MethodsThe inclusion criteria comprised individuals meeting the ACR/EULAR 2016 criteria who underwent MSGB with an infiltration of more than 50 lymphocytes and received clinical diagnosis between September 2017 and December 2018. Patients with inadequate biopsy samples were excluded. The number of lymphocytic foci and their lymphoid composition in MSGB were assessed using immunofluorescence staining. Major organ damage and improvements in the EULAR Sjögren’s Syndrome Disease Activity Index (ESSDAI) were measured. Statistical analyses, including Cox and linear regressions, were conducted.ResultsA total of 78 patients with at least one lymphocytic focus were included in the study. The presence of higher T-cell counts in lymphocytic foci in MSGB was associated with severe disease flare, and a logarithmic transformation of T-cell count indicated increased risk (HR 1.96, 95% CI 0.91-4.21). Improvements in the ESSDAI were associated with higher total lymphocyte count and T- and B-cell numbers in the lymphoid composition of the lymphocytic foci. Seropositive patients exhibited higher T CD4+ cell numbers. Correlation analysis showed negative associations between age and lymphocytic foci and the T-cell count. Positive correlations were observed between antinuclear antibody (ANA) titers and total lymphocyte numbers.DiscussionPatients with a higher number of T cells in the lymphocytic infiltrates of lymphocytic foci may have a two-fold risk of severe disease flare. The number of B cells and T CD4+ cells in the lymphocytic infiltrates of lymphocytic foci showed a weak but positive relation with the ESSDAI improvement during follow-up. Age and seropositivity appeared to influence the lymphoid composition of the lymphocytic foci.

BackgroundThe literature on associations of circulating concentrations of minerals and vitamins with risk of colorectal cancer is limited and inconsistent. Evidence from randomized controlled trials (RCTs) to support the efficacy of dietary modification or nutrient supplementation for colorectal cancer prevention is also limited.ObjectivesTo complement observational and RCT findings, we investigated associations of genetically predicted concentrations of 11 micronutrients (β-carotene, calcium, copper, folate, iron, magnesium, phosphorus, selenium, vitamin B-6, vitamin B-12, and zinc) with colorectal cancer risk using Mendelian randomization (MR).MethodsTwo-sample MR was conducted using 58,221 individuals with colorectal cancer and 67,694 controls from the Genetics and Epidemiology of Colorectal Cancer Consortium, Colorectal Cancer Transdisciplinary Study, and Colon Cancer Family Registry. Inverse variance-weighted MR analyses were performed with sensitivity analyses to assess the impact of potential violations of MR assumptions.ResultsNominally significant associations were noted for genetically predicted iron concentration and higher risk of colon cancer [ORs per SD (ORSD): 1.08; 95% CI: 1.00, 1.17; P value = 0.05] and similarly for proximal colon cancer, and for vitamin B-12 concentration and higher risk of colorectal cancer (ORSD: 1.12; 95% CI: 1.03, 1.21; P value = 0.01) and similarly for colon cancer. A nominally significant association was also noted for genetically predicted selenium concentration and lower risk of colon cancer (ORSD: 0.98; 95% CI: 0.96, 1.00; P value = 0.05) and similarly for distal colon cancer. These associations were robust to sensitivity analyses. Nominally significant inverse associations were observed for zinc and risk of colorectal and distal colon cancers, but sensitivity analyses could not be performed. None of these findings survived correction for multiple testing. Genetically predicted concentrations of β-carotene, calcium, copper, folate, magnesium, phosphorus, and vitamin B-6 were not associated with disease risk.ConclusionsThese results suggest possible causal associations of circulating iron and vitamin B-12 (positively) and selenium (inversely) with risk of colon cancer.

¿Pueden cometerse violaciones por engaño? La respuesta depende de qué signifique la palabra «consentimiento» del art. 178.1 CP. Este trabajo empieza poniendo de relieve que dicha palabra tiene, al menos, dos significados: uno débil (aceptación) y otro fuerte (aceptación libre y consciente). Tras exponer las consecuencias de interpretar de un modo u otro el «consentimiento» del art. 178.1 CP, se concluye que dicha palabra significa, simplemente, «aceptación». De esta forma, se niega la posibilidad de castigar como violaciones las relaciones sexuales que han sido aceptadas debido a un engaño (por ejemplo, dando a entender que una persona es soltera, rica, etc.). Sin embargo, más adelante se muestra que los engaños no solo pueden emplearse para lograr que otro acepte una relación sexual, sino también para ocultar la realización de un acto sexual que no se ha aceptado en absoluto. Esto sucede cuando se oculta alguno de los elementos que definen un acto sexual: el contacto corporal que implica o su naturaleza sexual. En estos casos, el sujeto engañado consiente un acto sexual (o médico) distinto al realizado. Y, por ello, dicho engaño puede dar lugar a una violación.

The research presented is positioned under the issue of hate speech prevalent in society, particularly its emergence in schools. In recent years, we have witnessed the presence of a phenomenon that is not new; however, it poses challenges to the teaching and learning processes for educators. Specifically, feminist movements and those advocating for diversity and nonconformity have triggered a strong response filled with violent and discriminatory messages and actions. To obtain some answers to this challenge, a case study was conducted with 6 teachers from various schools in Chile. Semi-structured interviews were carried out to explore, from their perspectives, aspects such as the origins of hate speech, the possibilities and proposals that teachers have for creating counter-narratives against hate, the effects of hate messages from gender perspectives in their teaching practices, and finally, the processes carried out with students. Among the main conclusions, it can be mentioned that there is a violent disruption that deepens gender inequalities, a situation that is becoming normalized and is of great concern for educators. Teachers express that they lack the tools and competencies to address these problems, other than continuing with the treatment of official content.

Abstract Background High-grade serous carcinoma (HGSC) is the most common and deadly subtype of ovarian cancer. Although most patients will initially respond to first-line treatment with a combination of surgery and platinum-based chemotherapy, up to a quarter will be resistant to treatment. We aimed to identify a new strategy to improve HGSC patient management at the time of cancer diagnosis (HGSC-1LTR). Methods A total of 109 ready-available formalin-fixed paraffin-embedded HGSC tissues obtained at the time of HGSC diagnosis were selected for proteomic analysis. Clinical data, treatment approach and outcomes were collected for all patients. An initial discovery cohort (n = 21) were divided into chemoresistant and chemosensitive groups and evaluated using discovery mass-spectrometry (MS)-based proteomics. Proteins showing differential abundance between groups were verified in a verification cohort (n = 88) using targeted MS-based proteomics. A logistic regression model was used to select those proteins able to correctly classify patients into chemoresistant and chemosensitive. The classification performance of the protein and clinical data combinations were assessed through the generation of receiver operating characteristic (ROC) curves. Results Using the HGSC-1LTR strategy we have identified a molecular signature (TKT, LAMC1 and FUCO) that combined with ready available clinical data (patients’ age, menopausal status, serum CA125 levels, and treatment approach) is able to predict patient response to first-line treatment with an AUC: 0.82 (95% CI 0.72–0.92). Conclusions We have established a new strategy that combines molecular and clinical parameters to predict the response to first-line treatment in HGSC patients (HGSC-1LTR). This strategy can allow the identification of chemoresistance at the time of diagnosis providing the optimization of therapeutic decision making and the evaluation of alternative treatment strategies. Thus, advancing towards the improvement of patient outcome and the individualization of HGSC patients’ care.

Abstract Objectives Early‐ and late‐onset Alzheimer's disease (EOAD and LOAD) share the same neuropathological traits but show distinct cognitive features. We aimed to explore baseline and longitudinal outcomes of global and domain‐specific cognitive function in a well characterized cohort of patients with a biomarker‐based diagnosis. Methods In this retrospective cohort study, 195 participants were included and classified according to their age, clinical status, and CSF AD biomarker profile: 89 EOAD, 37 LOAD, 46 young healthy controls (age ≤ 65 years), and 23 old healthy controls (>65 years). All subjects underwent clinical and neuropsychological assessment, neuroimaging, APOE genotyping and lumbar puncture. Results We found distinct neuropsychological profiles between EOAD and LOAD at the time of diagnosis. Both groups showed similar performances on memory and language domains, but the EOAD patients displayed worsened deficits in visual perception, praxis, and executive tasks (p

Introduction: The standard treatment for locally advanced rectal cancer (LARC) is neoadjuvant chemoradiotherapy (nCRT). To select patients who would benefit the most from nCRT, there is a need for predictive biomarkers. The aim of this study was to evaluate the role of clinical, pathological, radiological, inflammation-related genetic, and hematological parameters in the prediction of post-nCRT response.Materials and methods:In silico analysis of published transcriptomics datasets was conducted to identify candidate genes, whose expression will be measured using quantitative Real Time PCR (qRT-PCR) in pretreatment formaline-fixed paraffin-embedded (FFPE) samples. In this study, 75 patients with LARC were prospectively included between June 2020—January 2022. Patients were assessed for tumor response in week 8 post-nCRT with pelvic MRI scan and rigid proctoscopy. For patients with a clinical complete response (cCR) and initially distant located tumor no immediate surgery was suggested (“watch and wait” approach). The response after surgery was assessed using histopathological tumor regression grading (TRG) categories from postoperative specimens by Mandard. Responders (R) were defined as patients with cCR without operative treatment, and those with TRG 1 and TRG 2 postoperative categories. Non-responders (NR) were patients classified as TRG 3-5.Results: Responders group comprised 35 patients (46.6%) and NR group 53.4% of patients. Analysis of published transcriptomics data identified genes that could predict response to treatment and their significance was assessed in our cohort by qRT-PCR. When comparison was made in the subgroup of patients who were operated (TRG1 vs. TRG4), the expression of IDO1 was significantly deregulated (p < 0.05). Among hematological parameters between R and NR a significant difference in the response was detected for neutrophil-to-monocyte ratio (NMR), initial basophil, eosinophil and monocyte counts (p < 0.01). According to MRI findings, non-responders more often presented with extramural vascular invasion (p < 0.05).Conclusion: Based on logistic regression model, factors associated with favorable response to nCRT were tumor morphology and hematological parameters which can be easily and routinely derived from initial laboratory results (NMR, eosinophil, basophil and monocyte counts) in a minimally invasive manner. Using various metrics, an aggregated score of the initial eosinophil, basophil, and monocyte counts demonstrated the best predictive performance.

Different sizing criteria for thermal energy storage (TES) has been developed through the years, regarding specific situations for thermal solar panels, which tend not to be representative for new, more complex systems, in which heating and cooling are provided through using also solar thermal collectors. This article aims to provide a simplified and elegant solution for future tank selection in a more variable combination of technologies, through the use of parametric simulation and an inhouse developed methodolgy.

Summary: Minichromosome Maintenance 8 Homologous Recombination Repair Factor (MCM8) and Minichromosome Maintenance 9 Homologous Recombination Repair Factor (MCM9) are recently discovered minichromosome maintenance proteins and are implicated in multiple DNA-related processes and pathologies, including DNA replication (initiation), meiosis, homologous recombination and mismatch repair. Consistent with these molecular functions, variants of MCM8/MCM9 may predispose carriers to disorders such as infertility and cancer and should therefore be included in relevant diagnostic testing. In this overview of the (patho)physiological functions of MCM8 and MCM9 and the phenotype of MCM8/MCM9 variant carriers, we explore the potential clinical implications of MCM8/MCM9 variant carriership and highlight important future directions of MCM8 and MCM9 research. With this review, we hope to contribute to better MCM8/MCM9 variant carrier management and the potential utilization of MCM8 and MCM9 in other facets of scientific research and medical care.

Abstract Hate speech has become a social problem that needs to be addressed urgently. In many cases, these discourses and ideologies arrive through the media and the internet, and they are transferred to educational contexts. Debates of this type should be addressed at school and should be channelled into a democratic debate, and into the definition of shared objectives through the development of counterspeeches and alternative narratives based on Human Rights. In this research, we investigate the capacity of future teachers (n = 114) to identify online hate speech and how they develop counterspeeches. The results show that the majority are able to identify hate speech. However, future teachers present more difficulties developing counterspeeches or complex alternative narratives, which can be transferred to educational practices. We conclude that teacher training needs to be redesigned if we want them to be able to face these problems in their future educational practice.

Introduction: Surgical planning for repair of giant hernias with loss of domain needs to consider patient comorbidities, potential risks and possible postoperative complications. Some postoperative complications are related to the increase in intra-abdominal pressure caused by the reintroduction of abdominal contents into the peritoneal space. Preoperative progressive pneumoperitoneum (PPP) increases the capacity of abdominal cavity prior to hernia repair and allows for better physiological postoperative adaptation. The aim of this study is to analyze perioperative and intraoperative characteristics as well as outcomes of a cohort of patients treated with PPP prior to giant hernia repair at a single, high volume center.Methods: Prospective, descriptive, observational single-center study including 50 patients undergoing PPP prior to hernia with loss of domain repair between January 2005 and June 2022. We analysed epidemiological, surgical and safety variables.Results: Fifty patients were included: 43 incisional hernias, 6 inguinal hernias and 1 umbilical hernia. Mean age was 66 years (36–85). Median insufflation time was 12 days (4–20) and median insufflated volume of ambient air was 10,036 cc. There were complications during PPP in nine patients: 2 decompensation of chronic respiratory disease and 7 subcutaneous emphysema. PPP was prematurely suspended in patients with respiratory decompensation. All patients with incisional and umbilical hernias underwent open repair with mesh placement. Preperitoneal repair was performed in inguinal hernias. Three cases of hernia recurrence were reported during the follow up.Conclusion: PPP is a safe and effective tool in the preoperative management of patients with giant hernias. It helps to achieve the decrease or absence of abdominal wall tension and can favour the results of complex eventroplasty techniques.

The increase in successful adaptations of serial crystallography at synchrotron radiation sources continues. To date, the number of serial synchrotron crystallography (SSX) experiments has grown exponentially, with over 40 experiments reported so far. In this work, we report the first SSX experiments with viscous jets conducted at ALBA beamline BL13-XALOC. Small crystals (15–30 µm) of five soluble proteins (lysozyme, proteinase K, phycocyanin, insulin and α-spectrin-SH3 domain) were suspended in lipidic cubic phase (LCP) and delivered to the X-ray beam with a high-viscosity injector developed at Arizona State University. Complete data sets were collected from all proteins and their high-resolution structures determined. The high quality of the diffraction data collected from all five samples, and the lack of specific radiation damage in the structures obtained in this study, confirm that the current capabilities at the beamline enables atomic resolution determination of protein structures from microcrystals as small as 15 µm using viscous jets at room temperature. Thus, BL13-XALOC can provide a feasible alternative to X-ray free-electron lasers when determining snapshots of macromolecular structures.

Three X-ray structures are presented of human aldehyde dehydrogenase family 1 member A3 (ALDH1A3), a potential cancer stem cell biomarker (alone, with NAD+ and with ATP) and structure determination performed using molecular replacement.

Abstract Despite recent advances in the management of BRCA1 mutated high-grade serous ovarian cancer (HGSC), the physiology of these tumors remains poorly understood. Here we provide a comprehensive molecular understanding of the signaling processes that drive HGSC pathogenesis with the addition of valuable ubiquitination profiling, and their dependency on BRCA1 mutation-state directly in patient-derived tissues. Using a multilayered proteomic approach, we show the tight coordination between the ubiquitination and phosphorylation regulatory layers and their role in key cellular processes related to BRCA1-dependent HGSC pathogenesis. In addition, we identify key bridging proteins, kinase activity, and post-translational modifications responsible for molding distinct cancer phenotypes, thus providing new opportunities for therapeutic intervention, and ultimately advance towards a more personalized patient care.

Locally advanced rectal cancer (LARC) presents a challenge in identifying molecular markers linked to the response to neoadjuvant chemoradiotherapy (nCRT). This study aimed to utilize a sensitive proteomic method, data-independent mass spectrometry (DIA-MS), to extensively analyze the LARC proteome, seeking individuals with favorable initial responses suitable for a watch-and-wait approach. This research addresses the unmet need to understand the response to treatment, potentially guiding personalized strategies for LARC patients. Post-treatment assessment included MRI scans and proctoscopy. This research involved 97 LARC patients treated with intense chemoradiotherapy, comprising radiation and chemotherapy. Out of 97 LARC included in this study, we selected 20 samples with the most different responses to nCRT for proteome profiling (responders vs. non-responders). This proteomic approach shows extensive proteome coverage in LARC samples. The analysis identified a significant number of proteins compared to a prior study. A total of 915 proteins exhibited differential expression between the two groups, with certain signaling pathways associated with response mechanisms, while top candidates had good predictive potential. Proteins encoded by genes SMPDL3A, PCTP, LGMN, SYNJ2, NHLRC3, GLB1, and RAB43 showed high predictive potential of unfavorable treatment outcome, while RPA2, SARNP, PCBP2, SF3B2, HNRNPF, RBBP4, MAGOHB, DUT, ERG28, and BUB3 were good predictive biomarkers of favorable treatment outcome. The identified proteins and related biological processes provide promising insights that could enhance the management and care of LARC patients.