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Abstract In this study, the objective is to understand the causal factors that influence the mental well-being of healthcare workers during the COVID-19 pandemic, using Karasek’s Job Demand Control Social Model (JDCS) as the research framework. For this purpose the database Eurofound’s Living Working and COVID-19 survey is used; it was carried out using sampling design techniques in all 27 countries of the European Union. A sample of 4626 employees in the health sector is used, and structural equation models are specified to analyze causality. The analysis revealed significant associations between several factors: physical and mental work demands (p

Abstract The scientific literature shows that children’s participation in video games is increasingly common. However, there is no analysis of the involvement of children in the development of video games promoting social science learning. The framework of the EU H2020 funded project “ALLINTERACT. Widening and diversifying citizen engagement in science” contributes to filling this gap by analysing the co-creation process between children, families, teachers, and researchers of a video game for children to distinguish between hoaxes and evidence to overcoming bullying. To this end, a 24-h Science Game Jam was recorded, which took place in a virtual space for group meetings in which five children, five family members, four teachers and four researchers participated in the co-creation of the video game and a collaborative document in the cloud including the guidelines of the video game, with their proposals for the development. Finally, they participated as well as in the co-creation of the video game itself. The key finding is that co-creation through an egalitarian dialogue, solidarity, and focus on scientific knowledge allowed these children to play a leading role in developing a video game where children of all educational stages learn to distinguish hoaxes and evidence in overcoming bullying. The involvement in science and the co-creation of science-based products benefited these children; as they were protagonists in science, they could express their concerns and the real problems they faced in their schools, which increased their scientific knowledge and strengthened their critical capacity about bullying. Furthermore, the adult participants also benefited from the knowledge provided by the children, especially in the development and creation of the video game.

Abstract Spinal muscular atrophy (SMA) is a leading genetic cause of infant mortality. The advent of approved treatments for this devastating condition has significantly changed SMA patients' life expectancy and quality of life. Nevertheless, these are not without limitations, and research efforts are underway to develop new approaches for improved and long‐lasting benefits for patients. Protein arginine methyltransferases (PRMTs) are emerging as druggable epigenetic targets, with several small‐molecule PRMT inhibitors already in clinical trials. From a screen of epigenetic molecules, we have identified MS023, a potent and selective type I PRMT inhibitor able to promote SMN2 exon 7 inclusion in preclinical SMA models. Treatment of SMA mice with MS023 results in amelioration of the disease phenotype, with strong synergistic amplification of the positive effect when delivered in combination with the antisense oligonucleotide nusinersen. Moreover, transcriptomic analysis revealed that MS023 treatment has minimal off‐target effects, and the added benefit is mainly due to targeting neuroinflammation. Our study warrants further clinical investigation of PRMT inhibition both as a stand‐alone and add‐on therapy for SMA.

Abstract Clinical and preclinical studies established that supplementing diets with ω3 polyunsaturated fatty acids (PUFA) can reduce hepatic dysfunction in nonalcoholic steatohepatitis (NASH) but molecular underpinnings of this action were elusive. Herein, we used multi‐omic network analysis that unveiled critical molecular pathways involved in ω3 PUFA effects in a preclinical mouse model of western diet induced NASH. Since NASH is a precursor of liver cancer, we also performed meta‐analysis of human liver cancer transcriptomes that uncovered betacellulin as a key EGFR‐binding protein upregulated in liver cancer and downregulated by ω3 PUFAs in animals and humans with NASH. We then confirmed that betacellulin acts by promoting proliferation of quiescent hepatic stellate cells, inducing transforming growth factor–β2 and increasing collagen production. When used in combination with TLR2/4 agonists, betacellulin upregulated integrins in macrophages thereby potentiating inflammation and fibrosis. Taken together, our results suggest that suppression of betacellulin is one of the key mechanisms associated with anti‐inflammatory and anti‐fibrotic effects of ω3 PUFA on NASH.

This research presents an approach to automatic multiple-choice question (MCQ) generation in the Spanish language, using mT5-based models. The process encompasses three crucial tasks: candidate answer extraction, answer-aware question generation, and distractor generation. A methodical pipeline is structured to seamlessly integrate these tasks, converting an input text into a systematic questionnaire. For model fine-tuning, the Stanford Question Answering Dataset is employed for the first two tasks, while a combination of three different multiple-choice question datasets, translated automatically into Spanish, is used for the distractor generation task. The efficiency of the models is then evaluated by using a triad of metrics, namely BLEU, ROUGE-L, and cosine similarity. The outcomes indicate a marginal deviation from the baseline model in the question generation task but demonstrate superior performance in the distractor generation task. Importantly, this research emphasizes the potential and effectiveness of language models for automating MCQ generation, providing a valuable contribution to the field and enhancing the understanding and application of such models in the context of the Spanish language. [ABSTRACT FROM AUTHOR]

The vegetation surrounding aquatic ecosystems contributes allochthonous sources of organic matter to the water bodies. In Andean-Patagonian catchments, several non-native species grow among native ones. Different sources of dissolved organic matter (DOM) may vary in their contribution, potentially affecting aquatic functioning. This study evaluates differences in DOM contributions from native and non-native plants, analyzing DOM reactivity through its optical properties. An outdoor experiment was conducted with DOM leaf leachates from two native (Maytenus boaria and Nothofagus dombeyi) and two invasive trees (Salix fragilis and Pinus contorta). We characterized DOM concentration and quality optically by UV–Visible and fluorescence spectroscopy and found differences in both quantity and quality between the different leaf leachates. The exotic S. fragilis presented up to 7 times higher dissolved organic carbon (DOC) values than the other species. We found that leachates response to light exposure depended on its DOM composition. Decreasing patterns of DOC absorbance and fluorescence were observed in all leachates over time. We detected a gradient in leaf leachate photoreactivity due to solar exposure: (S. fragilis > P. contorta > M. boaria = N. dombeyi). Overall, our work shows that the invasive plants studied produce larger amounts of degradable DOM than some local native species. [ABSTRACT FROM AUTHOR]

ADAS (Advanced Driver Assistance Systems) are becoming increasingly popular in on-road vehicles due to their safety, productivity, and cost savings. In the same way, off-road vehicles can benefit from ADAS systems to improve the security of drivers and workers in industrial settings. In this work, we study, design, and develop a novel security system to be integrated into industrial vehicles. This system is built to provide one-way Human Computer Interaction, from the computer to the human, so providing, through the interaction with the ADAS system, feedback to drivers about their surroundings, such as nearby workers, and thus helping to avoid collisions and prevent incidents. The study evaluates the quality of different feedback mechanisms, with the goal of designing the ADAS that produces the best User eXperience (UX). These feedback mechanisms are generated by LEDs in different display formats and colors, as well as with haptic feedback. We created a hybrid testbed using a realistic ADAS and a forklift simulator, integrating the system into a physical structure that resembles an industrial vehicle (a forklift) and used a computer-based simulation of a warehouse to gather the information from users. We performed a study with 36 people for the evaluation of the different feedback mechanisms tested, evaluating the results both from an objective point of view based on the results of the simulation, and a subjective point of view through a questionnaire and the stress of the users in each test. [ABSTRACT FROM AUTHOR]

In sheltered employment centres, staff planning and scheduling activities are critical for operations managers. A generic framework is not easy to set up not only because legal issues are diverse and differ among these service organization types, but one worker may not fit in anywhere at any time. This complexity is greater when workers with specific needs perform work activities in many labour enclaves and different sectors. In this paper, a mixed-integer linear model to solve workers' shift assignments to other workplaces and various activities to form teams is proposed. The novelty of the proposed model lies in considering specific features, such as the skills matrix and the affinity matrix, between the different actors in a labour enclave. The model is validated using real instances from a case study, and several objectives are tested and discussed. The decision support system that sustains the model is introduced and managerial issues are discussed. [ABSTRACT FROM AUTHOR]

Background: This study presents a laparoscopic surgical protocol for right hemicolectomy and D3 lymphadenectomy (R-D3L) in right colon cancer and reports the oncological outcomes based on a prospective series. Methods: The study comprises two phases. In the first phase, a dynamic demonstration of the R-D3L surgical protocol is provided through textual explanation, illustrations, and edited surgical videos. The protocol emphasizes technical steps such as dissection of the embryological plane of the right mesocolon, high tie of ileocolic vessels, surgical trunk of Gillot dissection, and high tie of superior right colic vein (SRCV). In the second phase, a prospective observational study was conducted involving patients undergoing R-D3L surgery with this protocol between July 2015 and July 2021. Demographic, perioperative, and postoperative variables are analyzed, along with anatomopathological variables and oncological outcomes. Results: A total of 33 patients were analyzed. Median operative time was 202 min. Perioperative bleeding occurred in 6%. Postoperative complications were mild (Clavien–Dindo III in 2%). Postoperative ileus was observed in 15%. No anastomotic dehiscence was reported. The median postoperative stay was 7 days. The median number of resected lymph nodes was 26, with 27% having positive nodes and 70% were classified as stage T3 or T4. After a median follow-up of 45 months, local recurrence, distant recurrence, and carcinomatosis rates were 0%. Mortality rate from other causes was 9%. Conclusion: The surgical protocol shown in the present study could help in the implementation of this technique in those units that consider it appropriate. [ABSTRACT FROM AUTHOR]

The widespread usage of machine learning systems and econometric methods in the credit domain has transformed the decision-making process for evaluating loan applications. Automated analysis of credit applications diminishes the subjectivity of the decision-making process. On the other hand, since machine learning is based on past decisions recorded in the financial institutions' datasets, the process very often consolidates existing bias and prejudice against groups defined by race, sex, sexual orientation, and other attributes. Therefore, the interest in identifying, preventing, and mitigating algorithmic discrimination has grown exponentially in many areas, such as Computer Science, Economics, Law, and Social Science. We conducted a comprehensive systematic literature review to understand (1) the research settings, including the discrimination theory foundation, the legal framework, and the applicable fairness metric; (2) the addressed issues and solutions; and (3) the open challenges for potential future research. We explored five sources: ACM Digital Library, Google Scholar, IEEE Digital Library, Springer Link, and Scopus. Following inclusion and exclusion criteria, we selected 78 papers written in English and published between 2017 and 2022. According to the meta-analysis of this literature survey, algorithmic discrimination has been addressed mainly by looking at the CS, Law, and Economics perspectives. There has been great interest in this topic in the financial area, especially the discrimination in providing access to the mortgage market and differential treatment (different fees, number of parcels, and interest rates). Most attention has been devoted to the potential discrimination due to bias in the dataset. Researchers are still only dealing with direct discrimination, addressed by algorithmic fairness, while indirect discrimination (structural discrimination) has not received the same attention. [ABSTRACT FROM AUTHOR]

Semaprochilodus taeniurus (Valenciennes 1821) are known to inhabit the middle and lower regions of the Amazon basin. This study presents the first record of this species in the Peruvian Amazon, in the Lizardo stream, a tributary of the Putumayo River, Loreto region. The specimens were identified using meristic, morphological, and morphometric features as well as DNA barcodes based on the mitochondrial COI gene. This new species record contributes to enhancing our understanding of fish diversity in the Peruvian Amazon. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis causes progressive joint destruction in the long term, causing a deterioration of the foot and ankle. A clinical practice guideline has been created with the main objective of providing recommendations in the field of podiatry for the conservative management of rheumatoid arthritis. Thus, healthcare professionals involved in foot care of adults with rheumatoid arthritis will be able to follow practical recommendations. A clinical practice guideline was created including a group of experts (podiatrists, rheumatologists, nurses, an orthopaedic surgeon, a physiotherapist, an occupational therapist and patient with rheumatoid arthritis). Methodological experts using GRADE were tasked with systematically reviewing the available scientific evidence and developing the information which serves as a basis for the expert group to make recommendations. Key findings include the efficacy of chiropody in alleviating hyperkeratotic lesions and improving short-term pain and functionality. Notably, custom and standardized foot orthoses demonstrated significant benefits in reducing foot pain, enhancing physical function, and improving life quality. Therapeutic footwear was identified as crucial for pain reduction and mobility improvement, emphasizing the necessity for custom-made options tailored to individual patient needs. Surgical interventions were recommended for cases which were non-responsive to conservative treatments, aimed at preserving foot functionality and reducing pain. Moreover, self-care strategies and education were underscored as essential components for promoting patient independence and health maintenance. A series of recommendations have been created which will help professionals and patients to manage podiatric pathologies derived from rheumatoid arthritis. [ABSTRACT FROM AUTHOR]

Abstract Multi‐omics analyses are used in microbiome studies to understand molecular changes in microbial communities exposed to different conditions. However, it is not always clear how much each omics data type contributes to our understanding and whether they are concordant with each other. Here, we map the molecular response of a synthetic community of 32 human gut bacteria to three non‐antibiotic drugs by using five omics layers (16S rRNA gene profiling, metagenomics, metatranscriptomics, metaproteomics and metabolomics). We find that all the omics methods with species resolution are highly consistent in estimating relative species abundances. Furthermore, different omics methods complement each other for capturing functional changes. For example, while nearly all the omics data types captured that the antipsychotic drug chlorpromazine selectively inhibits Bacteroidota representatives in the community, the metatranscriptome and metaproteome suggested that the drug induces stress responses related to protein quality control. Metabolomics revealed a decrease in oligosaccharide uptake, likely caused by Bacteroidota depletion. Our study highlights how multi‐omics datasets can be utilized to reveal complex molecular responses to external perturbations in microbial communities.

The application of advanced embodied technologies, particularly virtual reality (VR), has been suggested as a means to induce the full-body illusion (FBI). This technology is employed to modify different facets of bodily self-consciousness, which involves the sense of inhabiting a physical form, and is influenced by cognitive inputs, affective factors like body dissatisfaction, individual personality traits and suggestibility. Specifically, VR-based Mirror Exposure Therapies are used for the treatment of anorexia nervosa (AN). This study aims to investigate whether the “Big Five” personality dimensions, suggestibility, body dissatisfaction and/or body mass index can act as predictors for FBI, either directly or acting as a mediator, in young women of similar gender and age as most patients with AN. The FBI of 156 healthy young women immersed in VR environment was induced through visuomotor and visuo-tactile stimulations, and then assessed using the Avatar Embodiment Questionnaire, comprising four dimensions: Appearance, Ownership, Response, and Multi-Sensory. Data analysis encompassed multiple linear regressions and SPSS PROCESS macro’s mediation model. The findings revealed that the “Big Five” personality dimensions did not directly predict FBI in healthy young women, but Openness to experience, Agreeableness, and Neuroticism exerted an indirect influence on some FBI components through the mediation of suggestibility. [ABSTRACT FROM AUTHOR]

Abstract Topoisomerase 3α (TOP3A) is an enzyme that removes torsional strain and interlinks between DNA molecules. TOP3A localises to both the nucleus and mitochondria, with the two isoforms playing specialised roles in DNA recombination and replication respectively. Pathogenic variants in TOP3A can cause a disorder similar to Bloom syndrome, which results from bi‐allelic pathogenic variants in BLM, encoding a nuclear‐binding partner of TOP3A. In this work, we describe 11 individuals from 9 families with an adult‐onset mitochondrial disease resulting from bi‐allelic TOP3A gene variants. The majority of patients have a consistent clinical phenotype characterised by bilateral ptosis, ophthalmoplegia, myopathy and axonal sensory‐motor neuropathy. We present a comprehensive characterisation of the effect of TOP3A variants, from individuals with mitochondrial disease and Bloom‐like syndrome, upon mtDNA maintenance and different aspects of enzyme function. Based on these results, we suggest a model whereby the overall severity of the TOP3A catalytic defect determines the clinical outcome, with milder variants causing adult‐onset mitochondrial disease and more severe variants causing a Bloom‐like syndrome with mitochondrial dysfunction in childhood.

Pancreatic ductal adenocarcinoma represents one of the solid tumors showing the worst prognosis worldwide, with a high recurrence rate after adjuvant or neoadjuvant therapy. Circulating tumor DNA analysis raised as a promising non-invasive tool to characterize tumor genomics and to assess treatment response. In this study, surgical tumor tissue and sequential blood samples were analyzed by next-generation sequencing and were correlated with clinical and pathological characteristics. Thirty resectable/borderline pancreatic ductal adenocarcinoma patients treated at the Hospital Universitario de Navarra were included. Circulating tumoral DNA sequencing identified pathogenic variants in KRAS and TP53, and in other cancer-associated genes. Pathogenic variants at diagnosis were detected in patients with a poorer outcome, and were correlated with response to neoadjuvant therapy in borderline pancreatic ductal adneocarcinoma patients. Higher variant allele frequency at diagnosis was associated with worse prognosis, and thesum of variant allele frequency was greater in samples at progression. Our results build on the potential value of circulating tumor DNA for non-metastatic pancreatic ductal adenocarcinoma patients, by complementing tissue genetic information and as a non-invasive tool for treatment decision. Confirmatory studies are needed to corroborate these findings. [ABSTRACT FROM AUTHOR]

Multiple-choice test generation is one of the most complex NLP problems, especially in languages other than English, where there is a lack of prior research. After a review of the literature, it has been verified that some methods like the usage of rule-based systems or primitive neural networks have led to the application of a recent architecture, the Transformer architecture, in the tasks of Answer Extraction (AE) and Question Generation (QG). Thereby, this study is centred in searching and developing better models for the AE and QG tasks in Spanish, using an answer-aware methodology. For this purpose, three multilingual models (mT5-base, mT0-base and BLOOMZ-560 M) have been fine-tuned using three different datasets: a translation to Spanish of the SQuAD dataset; SQAC, which is a dataset in Spanish; and their union (SQuAD + SQAC), which shows slightly better results. Regarding the models, the performance of mT5-base has been compared with that found in two newer models, mT0-base and BLOOMZ-560 M. These models were fine-tuned for multiple tasks in literature, including AE and QG, but, in general, the best results are obtained from the mT5 models trained in our study with the SQuAD + SQAC dataset. Nonetheless, some other good results are obtained from mT5 models trained only with the SQAC dataset. For their evaluation, the widely used BLEU1-4, METEOR and ROUGE-L metrics have been obtained, where mT5 outperforms some similar research works. Besides, CIDEr, SARI, GLEU, WER and the cosine similarity metrics have been calculated to present a benchmark within the AE and QG problems for future work. [ABSTRACT FROM AUTHOR]

Background: Rectal cancer (RC) is a surgical challenge due to its technical complexity. The double-stapled (DS) technique, a standard for colorectal anastomosis, has been associated with notable drawbacks, including a high incidence of anastomotic leak (AL). Low anterior resection with transanal transection and single-stapled (TTSS) anastomosis has emerged to mitigate those drawbacks. Methods: Observational study in which it described the technical aspects and results of the initial group of patients with medium-low RC undergoing elective laparoscopic total mesorectal excision (TME) and TTSS. Results: Twenty-two patients were included in the series. Favourable postoperative outcomes with a median length of stay of 5 days and an AL incidence of 9.1%. Importantly, all patients achieved complete mesorectal excision with tumour-free margins, and no mortalities were reported. Conclusion: TTSS emerges as a promising alternative for patients with middle and lower rectal tumours, offering potential benefits in terms of morbidity reduction and oncological integrity compared with other techniques. [ABSTRACT FROM AUTHOR]

Background: Reconstructive microsurgery techniques using vascularized bone grafts have revolutionized the treatment of complex cases associated with recalcitrant non-unions or osteomyelitis. The medial femoral corticoperiosteal flap (MFCP flap) has emerged as a valuable option in bone reconstruction. Its clinical applications have been extended over the years considering this flap from non-unions with minimal bone lost, up to large intercalary defects of the upper and lower extremities. This article aims to present the clinical applications and outcomes of the MFCP flap in various reconstructive scenarios. Methods: Seventy-nine patients with persistent non-union and bone defects of the upper and lower limb were evaluated from June 2008 to October 2020. All of them were reconstructed with a corticoperiosteal flap from the medial femoral condyle in our hospital. Previous procedures, bone gap and type of flap used were recorded. Postoperative functional status was assessed with time of bone healing, complications and clinical final outcome. Results: Radiological evidence of bone union was observed at 4.09 months (range 2–9). Healing rate was 97% with periosteal corticocancellous flaps (PCC flaps) and 93% with corticoperiosteal flaps (CP flaps). Average follow-up was 14.5 months (range 5–28). There were no significant donor site complications. Conclusions: The MFCP flap offers a versatile and reliable option for bone reconstruction. Its ability to provide vascularized bone tissue with low morbidity enhances the healing process and improves outcomes. The MFCP flap has been increasing its applications and it serves as a valuable option in the treatment of recalcitrant non-unions or bony defects irrespective of site and size up to 5 cm in the upper and lower extremities. [ABSTRACT FROM AUTHOR]

With the advancement of artificial intelligence, autonomous machines are featured with the ability to diagnose and assess the structural health of different systems. This paper presents a scalable mobile platform employed to autonomously and intelligently detect online small cracks on roads using a live camera feed and Artificial Intelligence (AI) methods. The robotic artifact is equipped with a vision-based localization system to enable autonomous navigation areas where GPS (Global Positioning System) may be poor or intermittent. The proposed approach runs at the edge a model of Convolutional Neuronal Networks (CNN) based on the Resnet 18 architecture to classify the image feed between cracks and those without cracks after training them with a combination of two public data sets and a data set generated in-house. The mobile robotic platform is scalable, depending on the particular context and requirements of the application. As opposed to off-line assessment tools, experimental results show the real-time capabilities of the system to autonomously navigate and detect cracks on a pavement structure with an accuracy of 95%. [ABSTRACT FROM AUTHOR]

Introduction and hypothesis: This study was aimed at determining the effect of sugammadex versus a combination of glycopyrrolate and neostigmine (GN) for neuromuscular reversal blockage on transient postoperative urinary retention (TPOUR) in patients undergoing a laparoscopic and robot-assisted laparoscopic hysterectomy. Methods: We conducted a retrospective cohort study in patients undergoing a laparoscopic or robotic hysterectomy between February 2017 and December 2021. Patients with and without concomitant procedures were included. Demographics and perioperative data were extracted from the patient's medical record. Before discharge, all patients were required to spontaneously void and have a post-void residual of less than 150 ml. Results: We identified 500 patients and 485 were included in the final analysis. We had 319 subjects who received sugammadex and 166 GN combination. Both groups had overall similar demographics and perioperative characteristics. Most patients had a conventional laparoscopy procedure (391 [82.5%]) compared with robotic (83 [17.5%]). Patients who received GN were significantly more likely to be discharged home with an indwelling catheter (odds ratio [OR], 1.82; 95% confidence interval [CI], 1.09—3.05). After adjusting for perioperative medications and sling implantation during the surgery a logistic regression model continued to demonstrate that patients who received GN had significantly higher odds of being discharged with a catheter (OR, 1.79; 95% CI, 1.03–3.12). Conclusions: Our findings suggest that sugammadex decreases the odds of TPOUR after laparoscopic hysterectomies with and without slings compared with the combination of GN. Additional prospective trials are required to confirm this finding. [ABSTRACT FROM AUTHOR]

Nanostructured materials have significantly influenced numerous scientific and technological areas, mainly due to the tuneability of their optical and electrical properties. When working with quantum dots (QDs)-based thin films, the high prevalence of trap states and low conductivity has been a remarkable challenge, which has been addressed by the fabrication of hybrid materials. However, on the road to improving their properties, fabrication of nanostructured hybrid materials, especially when involving 2D nanomaterials, still poses a challenging task, particularly when solution-processed approaches are considered. In the current work, the fabrication of a solution-processed QDs-2D nanomaterial hybrid, comprising PbS QDs and thermally reduced graphene oxide (rGO) is discussed. This study explores the nanostructured hybrid material's behavior when varying the weight percent ratio between the constituents, revealing a substantial impact of this parameter on the optoelectronic properties of the resulting hybrid material; particularly affecting the photogenerated charge carrier transfer, charge carrier mobility, charge carrier concentration and resistivity. Physical characterization of the hybrid material revealed a dramatic change in the interaction between the PbS QDs and the rGO as the weight percent of rGO increased in the hybrid material, showing a clear reduction of PbS QDs coverage on rGO's surface, which also produced an increment in the signals related to the oxidation of PbS QDs and rGO. The sample with 5% wt. of rGO showed optimal optoelectronic properties for possible applications in photodetector technologies or solar cells, displaying a high photogenerated current with a charge carrier mobility, charge carrier concentration, and resistivity of approximately 2.26 cm2/V-s, 1.27 × 1014 cm−3 and 2.18 × 104 Ω-cm, respectively. These findings serve as a foundational basis for the development of efficient optoelectronic devices based on this type of nanostructured hybrid material. [ABSTRACT FROM AUTHOR]

Abstract Defects in homologous recombination repair (HRR) in tumors correlate with poor prognosis and metastases development. Determining HRR deficiency (HRD) is of major clinical relevance as it is associated with therapeutic vulnerabilities and remains poorly investigated in sarcoma. Here, we show that specific sarcoma entities exhibit high levels of genomic instability signatures and molecular alterations in HRR genes, while harboring a complex pattern of chromosomal instability. Furthermore, sarcomas carrying HRDness traits exhibit a distinct SARC‐HRD transcriptional signature that predicts PARP inhibitor sensitivity in patient‐derived sarcoma cells. Concomitantly, HRDhigh sarcoma cells lack RAD51 nuclear foci formation upon DNA damage, further evidencing defects in HRR. We further identify the WEE1 kinase as a therapeutic vulnerability for sarcomas with HRDness and demonstrate the clinical benefit of combining DNA damaging agents and inhibitors of DNA repair pathways ex vivo and in the clinic. In summary, we provide a personalized oncological approach to treat sarcoma patients successfully.

Abstract Paneth cells are versatile secretory cells located in the crypts of Lieberkühn of the small intestine. In normal conditions, they function as the cornerstones of intestinal health by preserving homeostasis. They perform this function by providing niche factors to the intestinal stem cell compartment, regulating the composition of the microbiome through the production and secretion of antimicrobial peptides, performing phagocytosis and efferocytosis, taking up heavy metals, and preserving barrier integrity. Disturbances in one or more of these functions can lead to intestinal as well as systemic inflammatory and infectious diseases. This review discusses the multiple functions of Paneth cells, and the mechanisms and consequences of Paneth cell dysfunction. It also provides an overview of the tools available for studying Paneth cells.

We describe the geographical variation in tree species composition across Amazonian forests and show how environmental conditions are associated with species turnover. Our analyses are based on 2023 forest inventory plots (1 ha) that provide abundance data for a total of 5188 tree species. Within-plot species composition reflected both local environmental conditions (especially soil nutrients and hydrology) and geographical regions. A broader-scale view of species turnover was obtained by interpolating the relative tree species abundances over Amazonia into 47,441 0.1-degree grid cells. Two main dimensions of spatial change in tree species composition were identified. The first was a gradient between western Amazonia at the Andean forelands (with young geology and relatively nutrient-rich soils) and central–eastern Amazonia associated with the Guiana and Brazilian Shields (with more ancient geology and poor soils). The second gradient was between the wet forests of the northwest and the drier forests in southern Amazonia. Isolines linking cells of similar composition crossed major Amazonian rivers, suggesting that tree species distributions are not limited by rivers. Even though some areas of relatively sharp species turnover were identified, mostly the tree species composition changed gradually over large extents, which does not support delimiting clear discrete biogeographic regions within Amazonia. Tree species turnover across Amazonian forests unveils sharp floristic transitional zones, that are linked with changes in soil fertility and climate. [ABSTRACT FROM AUTHOR]

Extended reality (XR) applications for education are usually associated with motivation, engagement, knowledge and experiences that are difficult to achieve in the real world. One example of such knowledge in military education is the threat-based approach to protection of civilians in armed conflicts. The Norwegian Defence University College (NDUC) educates officers on the threat-based approach. This approach challenges conventional military practice, introducing new ways of thinking about what military forces can and cannot do to protect civilians from violence. Today, militaries are expected to protect civilians from perpetrators that target them as part of their warfare, expanding their responsibilities under International Humanitarian Law. This expansion of tasks represents "troublesome knowledge" for many military officers and demands a deeper understanding of the rationales and strategies driving perpetrators' targeting of civilians. To overcome this pedagogical challenge, we developed an XR-supported educational program combining immersive experiences and pedagogical approaches, including combined 360°-videos and embodiment, dialogue with virtual humans and collaborative VR-landscapes to encourage immersive peer-to-peer learning. The results are encouraging, suggesting high levels of acceptance by learners of the threat-based concept, an effect on stimulating critical discussion and a positive reaction to XR-supported learning. [ABSTRACT FROM AUTHOR]

Juvenile Temporal Arteritis (JTA) is a rare non-granulomatous vasculitis affecting the superficial temporal arteries, mostly in individuals under 45 years old. It is often misdiagnosed due to its benign nature and the absence of systemic symptoms. Herein, we present a case report of a 40-year-old woman who initially presented with painless nodules in the left temporal area. Following a biopsy, the patient developed additional nodules not only in the same temple but also on the contralateral side. Remarkably, these nodules underwent spontaneous regression without further treatment, highlighting the variability in JTA's course and distinctive response to intervention. In addition, through a systematic literature review of 43 case reports – 17 with bilateral involvement – we aimed to thoroughly understand the clinical and histopathological findings, diagnostic processes, and treatment responses in JTA, with an emphasis on cases with bilateral involvement. Findings indicate that JTA typically presents as painless or painful temporal nodules, rarely accompanied by other non-specific symptoms, making histopathological examination crucial for accurate diagnosis. Collectively, our work provides the most extensive account of bilateral JTA cases to date. It emphasizes the need for clinical awareness of this condition, contributes valuable data to the limited information available on this rare condition and serves as a stepping-stone for further inquiry. The main takeaway from this review is the variable nature of JTA and the importance of histopathology in diagnosis, which helps clinicians avoid excessive testing and overtreatment and anticipate possible spontaneous resolution. [ABSTRACT FROM AUTHOR]

Modern computing infrastructures are evolving due to virtualisation, especially with the advent of 5G and future technologies. While this transition offers numerous benefits, it also presents challenges. Consequently, understanding these complex systems, including networks, services, and their interconnections, is crucial. This paper introduces ServiceNet, a groundbreaking architecture that accurately performs the important task of providing understanding of a multi-tenant architecture by discovering the complete topology, crucial in the realm of high-performance distributed computing. Experimental results have been carried out in different scenarios in order to validate our approach, demonstrating the effectiveness of our approach in comprehensive multi-tenant topology discovery. The experiments, involving up to forty tenant, highlight the adaptability of ServiceNet as a valuable tool for real-time monitoring in topology discovery purposes, even in challenging scenarios. [ABSTRACT FROM AUTHOR]

We extend the method of controlled Lagrangians to nonholonomic Euler–Poincaré equations with advected parameters, specifically to those mechanical systems on Lie groups whose symmetry is broken not only by a potential force but also by nonholonomic constraints. We introduce advected-parameter-dependent quasivelocities in order to systematically eliminate the Lagrange multipliers in the nonholonomic Euler–Poincaré equations. The quasivelocities facilitate the method of controlled Lagrangians for these systems, and lead to matching conditions that are similar to those by Bloch, Leonard, and Marsden for the standard holonomic Euler–Poincaré equation. Our motivating example is what we call the pendulum skate, a simple model of a figure skater developed by Gzenda and Putkaradze. We show that the upright spinning of the pendulum skate is stable under certain conditions, whereas the upright sliding equilibrium is always unstable. Using the matching condition, we derive a control law to stabilize the sliding equilibrium. [ABSTRACT FROM AUTHOR]

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Background: Nonfunctioning pituitary adenomas (NFPAs) are a significant subtype of pituitary tumors, accounting for 30% of all pituitary tumors and 10–20% of intracranial tumors. The primary treatment for NFPAs is resection, but complete resection is often challenging due to the tumor's proximity to critical structures, leading to frequent recurrences. Stereotactic radiosurgery (SRS) has emerged as a viable treatment option for recurrent or residual NFPAs, but its long-term efficacy and safety profile require further investigation. Methods: This systematic review followed PRISMA guidelines and included studies published up to February 2024. We searched MEDLINE, Embase, and Cochrane databases for studies evaluating SRS for recurrent/residual NFPAs. Inclusion criteria focused on studies reporting outcomes and complications of SRS, while exclusion criteria omitted case reports, case series, and non-English studies. Data extracted included demographic details, dosimetry parameters, and follow-up durations. The risk of bias was assessed using the ROBINS-I tool, and statistical analyses were performed using single-arm meta-analyses. Results: A total of 24 studies involving 3,781 patients were included. The mean follow-up duration was 60 months. Tumor control was achieved in approximately 92.3% of patients. The risk of developing hypopituitarism post-SRS was 13.62%, while the risk for panhypopituitarism was 2.55%. New visual field deficits occurred in 3.94% of patients. Cranial nerve deficits were rare, with event rates below 1% for CN III, CN V, and CN VI. Conclusion: SRS is effective in managing recurrent or residual NFPAs, achieving high tumor control rates. However, the risk of hypopituitarism remains a significant concern, necessitating regular endocrinological monitoring. While generally safe, the potential for new visual field deficits and other cranial nerve deficits must be considered. SRS remains a valuable treatment option, but clinicians should be aware of its potential complications. [ABSTRACT FROM AUTHOR]

Purpose: To identify clinical and radiological factors associated with a higher risk of developing a severe pituitary apoplexy (PA). Methods: Multicenter retrospective study of patients presenting with clinical PA in three Spanish tertiary hospitals of Madrid between 2008 and 2022. We classified PA as severe when presenting with an altered level of consciousness (Glasgow Coma Scale (GCS) < 15) or visual involvement. Results: A total of 71 PA cases were identified, of whom 80.28% (n = 57) were classified as severe PA. The median age was 60 (18 to 85 years old) and 67.6% (n = 48) were male. Most patients had macroadenomas, except for one patient with a microadenoma of 9 mm. Headache was the most common presenting symptom (90.1%) and anticoagulation was the most frequent predisposing risk factor, but it was not associated with a higher risk for severe PA (odds ratio [OR] 1.13 [0.21–5.90]). Severe cases were associated with male gender (OR 5.53 [1.59–19.27]), tumor size >20 mm (OR 17.67 [4.07–76.64]), and Knosp grade ≥2 (OR 9.6 [2.38–38.73]). In the multivariant analysis, the only variables associated with a higher risk for severe PA were tumor size and Knosp grade. Surgery was more common in severe PA than in non-severe (91.2% vs. 64.3%, P = 0.009). Conclusion: A tumor size >20 mm and cavernous sinus invasion are risk factors for developing a severe PA. These risk factors can stratify patients at a higher risk of a worse clinical picture, and subsequently, more need of decompressive surgery. [ABSTRACT FROM AUTHOR]

Purpose: There is a tendency to use data generated for adults in the management of pediatric Differentiated Thyroid Carcinoma, neglecting the clinical peculiarities of this condition in childhood. This study aimed to assess and compare the clinical-epidemiological characteristics and their significance in the evolution of thyroid carcinoma diagnosed in childhood across different age groups. Methods: Seventy-seven patients diagnosed with Differentiated Thyroid Carcinoma (DTC) up to 21 years old were selected and divided into different age groups: up to 10 years, 11 to 18 years, and 19 to 21 years old. Clinical-epidemiological data and their influence in the disease progression were analyzed and compared across age groups. Results: Patients diagnosed below 10 years of age were associated with tumors showing extrathyroidal extension, metastasis in regional lymph nodes, higher levels of stimulated thyroglobulin in the diagnostic iodine-131 whole-body scan (WBS), and under TSH suppression in the last assessment. Additionally, pulmonary metastasis were associated in both diagnostic and post-radioiodine dose WBSs in these younger patients. Analysis of findings in the post-radioiodine therapy WBS revealed significant differences between all age groups (p = 0.0029). The time of diagnosis was identified as a factor associated with an excellent response in subgroups up to 18 years and up to 21 years. No factors associated with dynamic responses over the 1st, 3rd and 5th years of follow-up and the persistence/recurrence of the disease were identified in the subgroup up to 18 years. In the subgroup up to 21 years, having an incomplete structural response in the 3rd year of follow-up increased the chances of recurrent or persistent response by 5.5 times, and by 32.6 times if found in the 5th year of follow-up. Conclusions: Younger patients exhibited more aggressive tumor characteristics and underwent more rigorous treatment. However, treatment response and disease status in the last assessment, whether free or recurrent/persistence, were similar when comparing the age groups of 11 to 18 and 19 to 21 years. Nonetheless, responses obtained in the 3rd and 5th years post-treatment emerged as factors associated with the persistence/recurrence of the disease in the last assessment in the age group up to 21 years but not in patients diagnosed up to 18 years, a relevant distinction considering the tumor behavior in defining the pediatric age range in thyroid cancer. [ABSTRACT FROM AUTHOR]

The sol–gel process was applied to prepare ZnO-saponite nanocomposite for environmental remediation and investigation of photocatalysis mechanisms. The nanocomposite followed the photodegradation of Rhodamine B (RhB) as a model dye under irradiation with visible light. The materials were characterized by X-ray diffraction, scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), diffuse reflectance spectroscopy, photoluminescence, Point of zero charges (Pcz), and Brunauer–Emmett–Teller (BET). Reuse, the effect of scavengers, and toxicity were also investigated. The results showed an effective incorporation of the semiconductor on the surface of the support, forming a hexagonal structure with the wurtzite phase of ZnO. The evaluation of texture and morphology showed the effective distribution of ZnO nanoparticles on the surface of the synthesized photocatalyst. The intensified adsorption/photocatalysis process using saponite-based nanocomposite achieved more than 85% RhB dye removal efficiency after 270 min. It followed presented pseudo-first-order kinetics with a constant equal to 6.627 × 10–1 min−1. Furthermore, the evaluation of the effect of scavengers indicated that alcohol played an important role in scavenging hydroxyl radicals. It was stable after evaluating the catalyst after successive cycles, maintaining its structure, as FTIR proved. Furthermore, the studied nanocomposites did not show evidence of toxicity, thus being promising candidates for application in the removal of polluting dye. [ABSTRACT FROM AUTHOR]

Fibropapillomatosis (FP) - tumour-associated chelonid alphaherpesvirus 5 (ChHV5; Scutavirus chelonidalpha5) - is a disease that affect marine turtles around the world, and characterized by the formation of cutaneous tumours that can appear anywhere on the body. We carried out a thorough literature search (from 1990 to 2024) in the feeding sites of North-western Mexico, a region that hosts important habitats for feeding, development, and reproduction for five of the seven existing sea turtle species. We found 18 reports recording a total of 32 cases of FP and/or ChHV5/Scutavirus chelonidalpha5 in coastal and insular areas of North-western Mexico. Baja California Sur resulted with the highest number of cases (75%). While the first case of ChHV5/Scutavirus chelonidalpha5 infection was reported in 2004, the presence of FP tumours was reported in 2014 and became more frequent between 2019 and 2024. The affected species were black, Chelonia mydas (50%), olive ridley, Lepidochelys olivacea (46.8%) and loggerhead turtles, Caretta caretta (3.2%). Tumours occurred mainly in anterior flippers (46.1%) and neck (22.5%), and most had a nodular and verrucous appearance with a rough surface. In the study region, there is a potential sign of the emergence of the ChHV5/Scutavirus chelonidalpha5 infections and FP disease during the last 20 years, with a rapid increase during the last 10 years. As long as infections by ChHV5/Scutavirus chelonidalpha5 and the prevalence of the FP disease may be potentially influenced by anthropogenic activities, a One Health approach is needed to understand and improve sea turtles' health. [ABSTRACT FROM AUTHOR]

Rationale: Motivational dysfunctions related to effort exertion are common in psychiatric disorders. Dopamine systems regulate exertion of effort and effort-based choice in humans and rodents. Objectives: Previous rodent studies mainly employed male rats, and it is imperative to conduct studies in male and female rats. Methods: The present studies compared the effort-related effects of IP injections of the dopamine antagonists ecopipam and haloperidol, and the vesicular monoamine transport-2 inhibitor tetrabenazine (TBZ), in male and female rats using the fixed ratio 5/chow feeding choice task. Results: Ecopipam (0.05–0.2 mg/kg) and haloperidol (0.05–0.15 mg/kg) induced a low-effort bias, decreasing lever pressing and increasing chow intake in males and females in the same dose range. With lever pressing, there was a modest but significant dose x sex interaction after ecopipam injection, but there was no significant interaction after administration of haloperidol. In the first study with TBZ (0.25-1.0 mg/kg), there was a robust sex difference. TBZ shifted choice from lever pressing to chow intake in male rats, but was ineffective in females. In a second experiment, 2.0 mg/kg affected choice behavior in both males and females. TBZ increased accumbens c-Fos immunoreactivity in a sex-dependent manner, with males significantly increasing at 1.0 mg/kg, while females showed augmented immunoreactivity at 2.0 mg/kg. Conclusions: The neural and behavioral effects of TBZ differed across sexes, emphasizing the importance of conducting studies in male and female rats. This research has implications for understanding the effort-related motivational dysfunctions seen in psychopathology. [ABSTRACT FROM AUTHOR]

Let Ω ⊂ R n be non-empty, open and proper. This paper is concerned with W b p (Ω) , the space of p-integrable Borel measures on Ω equipped with the partial transportation metric introduced by Figalli and Gigli that allows the creation and destruction of mass on ∂ Ω . Alternatively, we show that W b p (Ω) is isometric to a subset of Borel measures with the ordinary Wasserstein distance, on the one point completion of Ω equipped with the shortcut metric δ (x , y) = min { ‖ x - y ‖ , dist (x , ∂ Ω) + dist (y , ∂ Ω) }. In this article we construct bi-Lipschitz embeddings of the set of unordered m-tuples in W b p (Ω) into Hilbert space. This generalises Almgren's bi-Lipschitz embedding theorem to the setting of optimal partial transport. [ABSTRACT FROM AUTHOR]

The purpose of this in vitro study was to evaluate the impact of the vertical level of the stopcock connecting the infusion line to the central venous catheter on start-up fluid delivery in microinfusions. Start-up fluid delivery was measured under standardized conditions with the syringe outlet and liquid flow sensors positioned at heart level (0 cm) and exposed to a simulated CVP of 10 mmHg at a set flow rate of 1 ml/h. Flow and intraluminal pressures were measured with the infusion line connected to the stopcock primarily placed at vertical levels of 0 cm, + 30 cm and − 30 cm or primarily placed at 0 cm and secondarily, after connecting the infusion line, displaced to + 30 cm and − 30 cm. Start-up fluid delivery 10 s after opening the stopcock placed at zero level and after opening the stopcock primarily connected at zero level and secondary displaced to vertical levels of + 30 cm and – 30 cm were similar (− 10.52 [− 13.85 to − 7.19] µL; − 8.84 [− 12.34 to − 5.33] µL and − 11.19 [− 13.71 to − 8.67] µL (p = 0.469)). Fluid delivered at 360 s related to 65% (zero level), 71% (+ 30 cm) and 67% (− 30 cm) of calculated infusion volume (p = 0.395). Start-up fluid delivery with the stopcock primarily placed at + 30 cm and − 30 cm resulted in large anterograde and retrograde fluid volumes of 34.39 [33.43 to 35.34] µL and − 24.90 [− 27.79 to − 22.01] µL at 10 s, respectively (p < 0.0001). Fluid delivered with the stopcock primarily placed at + 30 cm and − 30 cm resulted in 140% and 35% of calculated volume at 360 s, respectively (p < 0.0001). Syringe infusion pumps should ideally be connected to the stopcock positioned at heart level in order to minimize the amounts of anterograde and retrograde fluid volumes after opening of the stopcock. [ABSTRACT FROM AUTHOR]

T14, a 14mer peptide, is significantly increased in the pre-symptomatic Alzheimer's disease brain, and growing evidence implies its pivotal role in neurodegeneration. Here, we explore the subsequent intracellular events following binding of T14 to its target α7 nicotinic acetylcholine receptor (nAChR). Specifically, we test how various experimental manipulations of PC12 cells impact T14-induced functional outcomes. Three preparations were compared: (i) undifferentiated vs. NGF-differentiated cells; (ii) cells transfected with an overexpression of the target α7 nAChR vs. wild type cells; (iii) cells transfected with a mutant α7 nAChR containing a mutation in the G protein-binding cluster, vs. cells transfected with an overexpression of the target α7 nAChR, in three functional assays – calcium influx, cell viability, and acetylcholinesterase release. NGF-differentiated PC12 cells were less sensitive than undifferentiated cells to the concentration-dependent T14 treatment, in all the functional assays performed. The overexpression of α7 nAChR in PC12 cells promoted enhanced calcium influx when compared with the wild type PC12 cells. The α7345–348 A mutation effectively abolished the T14-triggered responses across all the readouts observed. The close relationship between T14 and the α7 nAChR was further evidenced in the more physiological preparation of ex vivo rat brain, where T30 increased α7 nAChR mRNA, and finally in human brain post-mortem, where levels of T14 and α7 nAChR exhibited a strong correlation, reflecting the progression of neurodegeneration. Taken together these data would make it hard to account for T14 binding to any other receptor, and thus interception at this binding site would make a very attractive and remarkably specific therapeutic strategy. [ABSTRACT FROM AUTHOR]

Background: Patients with peritoneal carcinomatosis often suffer from loss of skeletal muscle mass and require extensive surgery. Multimodal prehabilitation may improve physical status but its benefits for these specific patients remain unknown. This study aimed to evaluate the effect of prehabilitation on functional walking capacity and skeletal muscle mass, as well as its association with postoperative complications. Patients and Methods: A prospective study of patients with peritoneal carcinomatosis following a home-based trimodal prehabilitation program was carried out. Functional walking capacity was assessed with the 6-min walk test (T6MWT), and by the appendicular skeletal muscle index (ASMI) estimated by bioelectrical impedance analysis. Data were collected at the first medical appointment and on the day before surgery. A 90-day postoperative morbidity was registered according to the Clavien–Dindo classification. Results: A total of 62 patients were included in the analysis. Women were more prevalent (77.4%) and peritoneal metastasis from ovarian origin accounted for 48.4%. Clavien II–V grades occurred in 30 (57.7%) patients. After prehabilitation, functional walking capacity improved by 42.2 m (39.62–44.72 m) compared with baseline data (p < 0.001), but no improvement was observed in the ASMI (p = 0.301). Patients able to walk at least 360 m after prehabilitation suffered fewer Clavien–Dindo II–V postoperative complications (p = 0.016). A T6MWT of less than 360 m was identified as an independent risk factor in the multivariable analysis (OR 3.99; 1.01–15.79 p = 0.048). Conclusions: This home-based trimodal prehabilitation program improved functional walking capacity but not ASMI scores in patients with peritoneal metastasis before surgery. A T6MWT of less than 360 m was found to be a risk factor for postoperative complications. [ABSTRACT FROM AUTHOR]

Background: Rectal tumors display varying degrees of response to total neoadjuvant therapy (TNT). We evaluated the performance of a convolutional neural network (CNN) in interpreting endoscopic images of either a non-complete response to TNT or local regrowth during watch-and-wait surveillance. Methods: Endoscopic images from stage II/III rectal cancers treated with TNT from 2012 to 2020 at a single institution were retrospectively reviewed. Images were labelled as Tumor or No Tumor based on endoscopy timing (before, during, or after treatment) and the tumor's endoluminal response. A CNN was trained using ResNet-50 architecture. The area under the curve (AUC) was analyzed during training and for two test sets. The main test set included images of tumors treated with TNT. The other contained images of local regrowth. The model's performance was compared to sixteen surgeons and surgical trainees who evaluated 119 images for evidence of tumor. Fleiss' kappa was calculated by respondent experience level. Results: A total of 2717 images from 288 patients were included; 1407 (51.8%) contained tumor. The AUC was 0.99, 0.98, and 0.92 for training, main test, and local regrowth test sets. The model performed on par with surgeons of all experience levels for the main test set. Interobserver agreement was good (k = 0.71–0.81). All groups outperformed the model in identifying tumor from images of local regrowth. Interobserver agreement was fair to moderate (k = 0.24–0.52). Conclusions: A highly accurate CNN matched the performance of colorectal surgeons in identifying a noncomplete response to TNT. However, the model demonstrated suboptimal accuracy when analyzing images of local regrowth. [ABSTRACT FROM AUTHOR]

Research demonstrates that stigma and resilience influence transgender peoples' healthcare use. Less is known about transgender Latinas in the U.S. South who face multilevel barriers to healthcare access. We used baseline data from the ChiCAS intervention study. Using logistic regression, we examined how stigma (perceived discrimination related to gender identity, race/ethnicity, sexual behavior and perceived documentation status and internalized transphobia), and resilience (ethnic group pride and social support) are associated with two healthcare outcomes (use of routine medical care and medically supervised gender-affirming hormones). We also explored barriers to accessing both types of care. After removing 13 participants with missing data, our sample size was 131 transgender Latinas in the U.S. South. Most participants (74.8%, n = 98) received routine medical care in the past year and 57.3% (n = 75) had ever received medically supervised gender-affirming hormones. Reports of discrimination were highest for gender identity and documentation status. Race/ethnicity-based discrimination was positively associated with accessing routine medical care in the past year (OR = 1.94, p = 0.048). Having more social support was positively associated with care (routine care: OR = 3.48, p = 0.002 and gender-affirming hormones: OR = 2.33, p = 0.003). The most commonly reported barriers to accessing both types of care included cost, insurance, and not knowing where to go. Findings highlight the importance of social support for healthcare use among transgender Latinas. Social support may be especially important when considering the unique experiences of discrimination faced by transgender Latinas in the U.S. South. [ABSTRACT FROM AUTHOR]

Purpose: RAS (KRAS/NRAS) mutational status on a tumor biopsy is mandatory to guide the best treatment in metastatic colorectal cancer (mCRC). Determining the RAS mutational status by tumor-tissue biopsy is essential in guiding the optimal treatment decision for mCRC. RAS mutations are negative predictive factors for the use of EGFR monoclonal antibodies. Cell-free DNA (cfDNA) analysis enables minimally invasive monitoring of tumor evolution. Methods/patients: PERSEIDA was an observational, prospective study assessing cfDNA RAS, BRAF and EGFR mutations (using Idylla™) in first-line mCRC, RAS wild-type (baseline tumor-tissue biopsy) patients (cohort 2). Plasma samples were collected before first-line treatment, after 20 ± 2 weeks, and at disease progression. Results: 117 patients were included (103 received panitumumab + chemotherapy as first-line treatment). At baseline, 7 (6.8%) patients had RAS mutations, 4 (3.9%) BRAF mutations and no EGFR mutations were detected (cfDNA, panitumumab + chemotherapy subpopulation [panitumumab + Ch]). The baseline RAS mutational status concordance between tissue and liquid biopsies was 94.0% (93.2%, panitumumab + Ch). At 20 weeks, only one patient in the study (included in the panitumumab + Ch) had an emerging cfDNA RAS mutation. No emerging BRAF or EGFR mutations were reported. At disease progression, 6 patients had emergent mutations not present at baseline (RAS conversion rate: 13.3% [6/45]; 15.0% [6/40], panitumumab + Ch). Conclusions: The concordance rate between liquid and solid biopsies at baseline was very high, as previously reported, while our results suggest a considerable emergence of RAS mutations during disease progression. Thus, the dynamics of the genomic landscape in ctDNA may provide relevant information for the management of mCRC patients. [ABSTRACT FROM AUTHOR]

Galls are plant neoformations induced by specialized parasites. Since gall inducers rely on reactive plant sites for gall development, variations in abiotic factors that affect plant phenology are expected to impact the life cycle of gall inducers. To test the hypothesis that different light conditions affect both host plant and gall inducer life cycles, we studied the system Eugenia uniflora (Myrtaceae) – Clinodiplosis profusa (Cecidomyiidae), comparing plants occurring in sunny and shaded environments. We mapped phenological differences among individuals of E. uniflora occurring in the two environments and related them to the influence of luminosity on the life cycle of the gall inducer. Shade plants showed lower intensity of leaf sprouting throughout the year compared to sun-exposed plants, especially during the rainy season. Young and mature galls are synchronized with the peak of leaf sprouting at the beginning of the rainy season, lasting longer in sun-exposed plants – approximately two months longer compared to shade plants. The greater light intensity positively impacts the formation and growth of leaves and galls, with an extended period available for their induction and growth. Thus, light is an important factor for the development of gallers, considering that variations in luminosity influenced not only the phenology of the host plant, but also determined the life cycle of gall inducers. Furthermore, changes in plant-environment interactions are expected to affect the life cycle and richness of other host plant—gall inducer systems. [ABSTRACT FROM AUTHOR]

To characterize the impact of a RFI signal on the effective carrier-to-noise power density ratio, C/N0, of a GNSS receiver is very important for civil aviation standardization procedures in order to define Radio Frequency Interference (RFI)/jamming robustness test for two reasons. First, the prediction of the effective C/N0 is fundamental to predict the minimum performance attainable by an airborne GNSS receiver and to adjust the tests accordingly. Second, the receiver’s estimation of the effective C/N0 can allow the detection of the jamming presence and thus can help the receiver to adapt to the RFI situation. This problematic is analyzed with the introduction of three C/N0 definitions, statistical C/N0 which is the statistical prediction of the effective C/N0, real C/N0 which is the true effective C/N0 faced by the receiver and estimated C/N0 which is the value provided by a C/N0 estimator. Three conditions of validity are given to establish a relationship of equality between the three terms: ergodicity, centered RFI contribution at the correlator output and C/N0 estimator characteristics. To evaluate this last condition, Narrow-Wideband Power Ratio (NWPR), Signal-to-Noise Variance (SNV), Beaulieu and Moments Methods (MM) estimators are inspected and their expected mean value in presence of a generic RFI is theoretically derived. Finally, a full analysis is conducted for a RFI chirp signal showing that not all chirp signals are able to allow a statistical prediction of its effective C/N0 (condition of validity 1) and that NWPR and SNV are the more robust estimators (condition of validity 3) against this type of RFI. [ABSTRACT FROM AUTHOR]

Introduction: Haemophilia A (HA) is a congenital bleeding disorder caused by a deficiency/absence of factor VIII (FVIII) and characterised by frequent, acute and prolonged spontaneous or traumatic bleeding events, often leading to haemophilic arthropathy and progressive joint deterioration. HA severity is characterized by endogenous FVIII activity: mild (> 5–40%), moderate (1–5%), or severe (< 1%). HA poses a substantial clinical and socioeconomic burden on people with HA (PWHA), their caregivers, and society. This analysis evaluates clinical and patient-centric outcomes of a cohort of individuals with non-inhibitor HA sampled from France, Germany, Italy, Spain, and the UK in the 'Cost of Haemophilia in Europe: A Socioeconomic Survey II' (CHESS II) study. Methods: CHESS II was a cross-sectional burden-of-illness study collecting clinical and socioeconomic data on adult (≥ 18 years) individuals with haemophilia A or B of any severity with or without inhibitors from eight European countries. Descriptive analyses were conducted examining physician-reported demographics, clinical and health resource utilisation information. PWHA-reported health-related quality of life (HRQoL) using the EQ-5D-5L and Work Productivity and Activity Impairment (WPAI) were also examined. Outcomes were stratified by HA severity and reported at country level. Results: Demographics and clinical characteristics of the cohort (N = 880) were generally consistent across countries. Individuals with severe HA experienced more frequent bleeding events and joint disease despite broad use of factor replacement therapy long-term prophylaxis. A minority of those with mild or moderate HA also experienced such challenges. HRQoL and workforce participation diminished, and chronic pain increased, with increasing HA severity. Conclusion: This analysis provides up-to-date insights on the impact of HA across five European countries. Increasing HA severity was generally associated with worse clinical outcomes, HRQoL and workforce participation. These findings suggest a place for continued evidence-based tailored treatment and clinical management approaches in addressing the residual burden of HA. [ABSTRACT FROM AUTHOR]