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Abstract Triple‐negative breast cancer (TNBC) often develops resistance to single‐agent treatment, which can be circumvented using targeted combinatorial approaches. Here, we demonstrate that the simultaneous inhibition of LOXL2 and BRD4 synergistically limits TNBC proliferation in vitro and in vivo. Mechanistically, LOXL2 interacts in the nucleus with the short isoform of BRD4 (BRD4S), MED1, and the cell cycle transcriptional regulator B‐MyB. These interactions sustain the formation of BRD4 and MED1 nuclear transcriptional foci and control cell cycle progression at the gene expression level. The pharmacological co‐inhibition of LOXL2 and BRD4 reduces BRD4 nuclear foci, BRD4‐MED1 colocalization, and the transcription of cell cycle genes, thus suppressing TNBC cell proliferation. Targeting the interaction between BRD4S and LOXL2 could be a starting point for the development of new anticancer strategies for the treatment of TNBC.

Abstract While cellular metabolism impacts the DNA damage response, a systematic understanding of the metabolic requirements that are crucial for DNA damage repair has yet to be achieved. Here, we investigate the metabolic enzymes and processes that are essential for the resolution of DNA damage. By integrating functional genomics with chromatin proteomics and metabolomics, we provide a detailed description of the interplay between cellular metabolism and the DNA damage response. Further analysis identified that Peroxiredoxin 1, PRDX1, contributes to the DNA damage repair. During the DNA damage response, PRDX1 translocates to the nucleus where it reduces DNA damage‐induced nuclear reactive oxygen species. Moreover, PRDX1 loss lowers aspartate availability, which is required for the DNA damage‐induced upregulation of de novo nucleotide synthesis. In the absence of PRDX1, cells accumulate replication stress and DNA damage, leading to proliferation defects that are exacerbated in the presence of etoposide, thus revealing a role for PRDX1 as a DNA damage surveillance factor.

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.

Abstract Inhibition of mTOR is the standard of care for lymphangioleiomyomatosis (LAM). However, this therapy has variable tolerability and some patients show progressive decline of lung function despite treatment. LAM diagnosis and monitoring can also be challenging due to the heterogeneity of symptoms and insufficiency of non‐invasive tests. Here, we propose monoamine‐derived biomarkers that provide preclinical evidence for novel therapeutic approaches. The major histamine‐derived metabolite methylimidazoleacetic acid (MIAA) is relatively more abundant in LAM plasma, and MIAA values are independent of VEGF‐D. Higher levels of histamine are associated with poorer lung function and greater disease burden. Molecular and cellular analyses, and metabolic profiling confirmed active histamine signaling and metabolism. LAM tumorigenesis is reduced using approved drugs targeting monoamine oxidases A/B (clorgyline and rasagiline) or histamine H1 receptor (loratadine), and loratadine synergizes with rapamycin. Depletion of Maoa or Hrh1 expression, and administration of an L‐histidine analog, or a low L‐histidine diet, also reduce LAM tumorigenesis. These findings extend our knowledge of LAM biology and suggest possible ways of improving disease management.

Abstract The altered metabolism of cancer can render cells dependent on the availability of metabolic substrates for viability. Investigating the signaling mechanisms underlying cell death in cells dependent upon glucose for survival, we demonstrate that glucose withdrawal rapidly induces supra‐physiological levels of phospho‐tyrosine signaling, even in cells expressing constitutively active tyrosine kinases. Using unbiased mass spectrometry‐based phospho‐proteomics, we show that glucose withdrawal initiates a unique signature of phospho‐tyrosine activation that is associated with focal adhesions. Building upon this observation, we demonstrate that glucose withdrawal activates a positive feedback loop involving generation of reactive oxygen species (ROS) by NADPH oxidase and mitochondria, inhibition of protein tyrosine phosphatases by oxidation, and increased tyrosine kinase signaling. In cells dependent on glucose for survival, glucose withdrawal‐induced ROS generation and tyrosine kinase signaling synergize to amplify ROS levels, ultimately resulting in ROS‐mediated cell death. Taken together, these findings illustrate the systems‐level cross‐talk between metabolism and signaling in the maintenance of cancer cell homeostasis.

As society experiences accelerated ageing, understanding the complex biological processes of human ageing, which are affected by a large number of variables and factors, becomes increasingly crucial. Artificial intelligence (AI) presents a promising avenue for ageing research, offering the ability to detect patterns, make accurate predictions, and extract valuable insights from large volumes of complex, heterogeneous data. As ageing research increasingly leverages AI techniques, we present a timely systematic literature review to explore the current state-of-the-art in this field following a rigorous and transparent review methodology. As a result, a total of 77 articles have been identified, summarised, and categorised based on their characteristics. AI techniques, such as machine learning and deep learning, have been extensively used to analyse diverse datasets, comprising imaging, genetic, behavioural, and contextual data. Findings showcase the potential of AI in predicting age-related outcomes, developing ageing biomarkers, and determining factors associated with healthy ageing. However, challenges related to data quality, interpretability of AI models, and privacy and ethical considerations have also been identified. Despite the advancements, novel approaches suggest that there is still room for improvement to provide personalised AI-driven healthcare services and promote active ageing initiatives with the ultimate goal of enhancing the quality of life and well-being of older adults. Overview of the literature review. [ABSTRACT FROM AUTHOR]

Purpose: Disease heterogeneity in coronavirus disease 2019 (COVID-19) may render the current one-size-fits-all treatment approach suboptimal. We aimed to identify and immunologically characterize clinical phenotypes among critically ill COVID-19 patients, and to assess heterogeneity of corticosteroid treatment effect. Methods: We applied consensus k-means clustering on 21 clinical parameters obtained within 24 h after admission to the intensive care unit (ICU) from 13,279 COVID-19 patients admitted to 82 Dutch ICUs from February 2020 to February 2022. Derived phenotypes were reproduced in 6225 COVID-19 ICU patients from Spain (February 2020 to December 2021). Longitudinal immunological characterization was performed in three COVID-19 ICU cohorts from the Netherlands and Germany, and associations between corticosteroid treatment and survival were assessed across phenotypes. Results: We derived three phenotypes: COVIDICU1 (43% of patients) consisted of younger patients with the lowest Acute Physiology And Chronic Health Evaluation (APACHE) scores, highest body mass index (BMI), lowest PaO2/FiO2 ratio, and a 90-day in-hospital mortality rate of 18%. COVIDICU2 patients (37%) had the lowest BMI, were older and had higher APACHE scores and mortality rate (24%) than COVIDICU1. Patients with COVIDICU3 (20%) were the eldest with the most comorbidities, the highest APACHE scores, acute kidney injury and metabolic dysregulations, and the highest mortality rate (47%). These patients also displayed the most pronounced inflammatory response. Corticosteroid therapy started at day 5 [2–9] after ICU admission and administered for 5 [3–7] days was associated with an increased risk for 90-day mortality in patients with the COVIDICU1 and COVIDICU2 phenotypes (hazard ratio [HR] 1.59 [1.09–2.31], p = 0.015 and HR 1.79 [1.42–2.26], p < 0.001, respectively), but not in patients with the COVIDICU3 phenotype (HR 1.08 [0.76–1.54], p = 0.654). Conclusion: Our multinational study identified three distinct clinical COVID-19 phenotypes, each exhibiting marked differences in demographic, clinical, and immunological features, and in the response to late and short-term corticosteroid treatment. [ABSTRACT FROM AUTHOR]

Background: Despite higher breast cancer screening rates, black women still are more likely to have late-stage disease diagnosed. This disparity is influenced in part by structural and interpersonal racism. This prospective study sought to determine how interpersonal factors, including perceived discrimination, influence screening and stage of disease at diagnosis. Methods: A prospective cohort study analyzed adult women with stages I to IV breast cancer from the Miami Breast Cancer Disparities Study. Perceived discrimination and mistrust of providers were assessed using previously validated questionnaires. Multivariable logistic regression was used to evaluate the odds of screening mammography utilization and late-stage breast cancer at diagnosis. Results: The study enrolled 342 patients (54.4 % Hispanic, 15.8 % white, and 17.3 % black). Multivariate regression, after control for both individual- and neighborhood-level factors, showed that a higher level of perceived discrimination was associated with greater odds of late-stage disease (adjusted odds ratio [aOR], 1.06; range, 1.01–1.12); p = 0.022) and lower odds of screening mammography (aOR, 0.96; range, 0.92–0.99; p = 0.046). A higher level of perceived discrimination also was negatively correlated with multiple measures of provider trust. Discussion: This study identified that high perceived level of discrimination is associated with decreased odds of ever having a screening mammogram and increased odds of late-stage disease. Efforts are needed to reach women who experience perceived discrimination and to improve the patient–provider trust relationship because these may be modifiable risk factors for barriers to screening and late-stage disease presentation, which ultimately have an impact on breast cancer survival. [ABSTRACT FROM AUTHOR]

There are more ways to synthesize a 100-amino acid (aa) protein (20100) than there are atoms in the universe. Only a very small fraction of such a vast sequence space can ever be experimentally or computationally surveyed. Deep neural networks are increasingly being used to navigate high-dimensional sequence spaces1. However, these models are extremely complicated. Here, by experimentally sampling from sequence spaces larger than 1010, we show that the genetic architecture of at least some proteins is remarkably simple, allowing accurate genetic prediction in high-dimensional sequence spaces with fully interpretable energy models. These models capture the nonlinear relationships between free energies and phenotypes but otherwise consist of additive free energy changes with a small contribution from pairwise energetic couplings. These energetic couplings are sparse and associated with structural contacts and backbone proximity. Our results indicate that protein genetics is actually both rather simple and intelligible.By experimentally sampling from sequence spaces larger than 1010 and using thermodynamic models, the genetic structure of at least some proteins can be well described, indicating that protein genetics is simpler than anticipated. [ABSTRACT FROM AUTHOR]

Purpose: The aim of the present study is to assess the role of indocyanine green (ICG) to evaluate distal ureteral vascularity during robot-assisted radical cystectomy (RARC) with intracorporeal urinary diversion and its impact on the incidence of benign ureteroenteric strictures (UES). Methods: The study included patients who underwent RARC for bladder cancer between 2018 and 2023. All patients included underwent intracorporeal urinary diversion with ileal conduit or neobladder. Bricker technique was performed in all ureteroenteric anastomosis. ICG was employed during the study period to evaluate ureteral vascularity. We divided patients into 2 groups depending on the utilization of ICG during surgery and compared demographic, clinicopathological and perioperative outcomes, including benign UES rates. Results: We identified 221 patients that underwent RARC with intracorporeal urinary diversion. Ileal conduit was performed in 173 (78.3%) patients and neobladder in 48 (21.7%) cases. A total of 142 (64.3%) and 79 (35.7%) patients were in the non-ICG and ICG group, respectively. With a median follow-up of the entire cohort of 21.1 months, there were no differences in the rate of benign UES after RARC between the non-ICG and the ICG group (p = 0.901). In the non-ICG group, 26 (18.3%) patients developed benign UES and in the ICG group 15 (19.0%) patients. Most of the strictures appeared in the left ureter in both groups (80.8% non-ICG vs. 66.7% ICG, p = 0.599). Median time to stricture diagnosis was 4 months (IQR 3-7.25) for the non-ICG and 3 months (IQR 2–5) for the ICG group (p = 0.091). The ICG group had a slightly greater length of ureter resected compared with the non-ICG group (1.5 vs. 1.3 cm, p = 0.007). Conclusion: In our experience, choosing to use ICG intraoperatively to evaluate distal ureteral vascularity may not reduce the rate of benign UES after robot-assisted radical cystectomy with intracorporeal urinary diversion and Bricker ureteroileal anastomosis. [ABSTRACT FROM AUTHOR]

Objective: Many stroke survivors still present with upper-limb paresis six months post-stroke, impacting their autonomy and quality of life (QoL). We designed an enriched Music-supported Therapy (eMST) program to reduce disability in this population. We evaluated the eMST's effectiveness in improving functional abilities and QoL in chronic stroke individuals compared to the conventional motor program Graded Repetitive Arm Supplementary Program (GRASP). Methods: We conducted a pragmatic two-arm parallel-group randomized controlled trial with a 3-month follow-up and masked assessment. The eMST involved playing instruments during individual self-administered and group music therapy sessions. The GRASP consisted of self-administered motor exercises using daily objects. Both interventions were completed at home with telemonitoring and involved four one-hour weekly sessions for 10 weeks. The primary outcome was upper-limb motor function measured with the Action Research Arm Test. Secondary outcomes included motor impairment, daily life motor performance, cognitive functions, emotional well-being, QoL, self-regulation, and self-efficacy. Intention-to-treat (ITT) and per-protocol (PP) analyses were conducted including participants who discontinued the intervention and those who completed it entirely, respectively. Results: Fifty-eight chronic stroke patients were randomized to the eMST-group (n = 26; age: 64.2 ± 12.5; 6 [23.1%] females; 2.8 ± 2.9 years post-stroke), and the control group (n = 32; age: 62.2 ± 12; 8 [25%] females; 1.8 ± 6.2 years post-stroke). The eMST-group had more participants achieving a clinically relevant improvement in motor impairment post-intervention than the control group for the ITT (55% vs 21.6%; OR = 4.5 (95% CI 1.4–14); p =.019) and PP analyses (60% vs 20%; OR = 6 (95% CI 1.5–24.7); p =.024), sustained at follow-up. The eMST-group reported greater improvements in emotion (difference = 11.1 (95% CI 0.8–21.5; p = 0.36) and participation (difference = 10.3 (95% CI 0.6–25.9); p = 0.41) subscales of QoL, and higher enjoyment during the sessions (difference = 1 (95% CI 0.3–1.5); p = 0.12). No changes were found in other outcomes. Conclusion: eMST demonstrated superiority over conventional motor rehabilitation program in enhancing upper-limb functions and QoL in chronic stroke individuals. Trial Registration: ClinicalTrials.gov (ID: NCT04507542). [ABSTRACT FROM AUTHOR]

The spatial mismatch between jobs and housing in cities creates long daily travels that exacerbate climate change, air pollution, and traffic congestion. Yet, not enough research on occupational differences has been done. This study first applies the Hidden Markov Mixture Model (H3M) to model travel patterns for different occupation groups in Hong Kong. Then, the Variational Bayesian Hierarchical EM algorithm is used to identify common lifestyle clusters. Next, a binary logistic regression is developed to examine whether the lifestyle clusters can be explained by jobs-housing balance. This study is among the first to consider travel patterns as a Markov process and apply H3M to examine jobs-housing balance by fine-grain occupation group. The method is transferable and universally applicable; and the results provide occupation-specific insights on jobs-housing balance in an Asian context. The research findings suggest that different occupation groups have different travel patterns in Hong Kong. Two lifestyle clusters, "balanced and compact activity space" and "work-oriented and extensive travels", are unveiled. Notably, the latter is associated a lower level of jobs-housing balance. Some occupations in the quaternary industry ("information and communications", "profession, science and technology", "real estate", and "finance and insurance") are having more serious jobs-housing imbalance. The paper concludes with a discussion on improving the occupation-specific jobs-housing balance in accordance with Hong Kong's future development goals. [ABSTRACT FROM AUTHOR]

The valorization of biogas as a renewable energy source faces a major obstacle regarding its purification. Siloxane is one of the impurities that cause problems such as damages to equipment of combustion engines, turbines, and boilers used for biogas conversion to heat and electricity. In this review, adsorption for siloxane removal is widely discussed, with two specific approaches: adsorbents sensitivity to water and regeneration, two essential points for industrial application. Thus, determining factors in adsorbents capacity, reusability, and water tolerance including textural properties, surface functional groups, and hydrophobicity are deeply analyzed. Studies oriented to the optimization of traditional adsorbents such as activated carbon, silica gel, and aluminosilicates as well as newly emerging adsorbents such as metal organic frameworks, graphene oxides, and waste-derived materials are studied in detail in terms of reusability and water tolerance. Although activated carbon is commercially used, its low selectivity, pore blockage due to siloxane polymerization, and unsuccessful regeneration make it disadvantageous. Silica gel, however, shows better reusability as a result of less adsorbent-adsorbate dissociation energy. In addition, aluminosilicates, despite its low adsorption capacity, proved to be more practical for real biogas due to their high hydrophobicity. Graphene oxide cost and energy efficiency in their synthesis make them more industrially appealing candidates despite their low adsorption capacity. Finally, metal organic frameworks demonstrated high selectivity, high adsorption capacity, and more efficient regeneration and therefore have more advantages and less drawbacks, although the number of published studies is still limited. [ABSTRACT FROM AUTHOR]

Inflammation is relevant in the pathogenesis and progression of heart failure (HF). Previous studies have shown that elevated high-sensitivity C-reactive protein (hsCRP) are associated with greater severity and may be associated with adverse outcomes. In this study, we sought to evaluate the prognostic role of hsCRP in a non-selected cohort of patients with acute HF. We prospectively included a multicenter cohort of 3,395 patients following an admission for acute HF. HsCRP levels were evaluated during the first 24 h following admission. Study endpoints were the risks of all-cause mortality, CV-mortality, and total HF readmissions. The mean age was 74.2 ± 11.2 years and 1,826 (53.8%) showed a left ventricular ejection fraction (LVEF) ≥ 50%. Median hsCRP was 12.9 mg/L (5.4–30 mg/L). Over a median follow-up of 1.8 (0.6–4.1) years, 1,574 (46.4%) patients died, and 1,341 (39.5%) patients were readmitted for worsening HF. After multivariable adjustment, hsCRP values were significantly and positively associated with a higher risk of all-cause and CV mortality (p = 0.003 and p = 0.001, respectively), as well as a higher risk of recurrent HF admissions (p < 0.001). These results remained consistent across important subgroups, such as LVEF, sex, age, or renal function. In patients with acute HF, hsCRP levels were independently associated with an increased risk of long-term death and total HF readmissions. [ABSTRACT FROM AUTHOR]

Background: Alveolar macrophages activation to the pro-inflammatory phenotype M1 is pivotal in the pathophysiology of Ventilator-Induced Lung Injury (VILI). Increased lung strain is a known determinant of VILI, but a direct correspondence between regional lung strain and macrophagic activation remains unestablished. [68Ga]Ga-DOTA-TATE is a Positron Emission Tomography (PET) radiopharmaceutical with a high affinity for somatostatin receptor subtype 2 (SSTR2), which is overexpressed by pro-inflammatory-activated macrophages. Aim of the study was to determine, in a porcine model of VILI, whether mechanical strain correlates topographically with distribution of activated macrophages detected by [68Ga]Ga-DOTA-TATE uptake. Methods: Seven anesthetized pigs underwent VILI, while three served as control. Lung CT scans were acquired at incremental tidal volumes, simultaneously recording lung mechanics. [68Ga]Ga-DOTA-TATE was administered, followed by dynamic PET scans. Custom MatLab scripts generated voxel-by-voxel gas volume and strain maps from CT slices at para-diaphragmatic (Para-D) and mid-thoracic (Mid-T) levels. Analysis of regional Voxel-associated Normal Strain (VoStrain) and [68Ga]Ga-DOTA-TATE uptake was performed and a measure of the statistical correlation between these two variables was quantified using the linear mutual information (LMI) method. Results: Compared to controls, the VILI group exhibited statistically significant higher VoStrain and Standardized Uptake Value Ratios (SUVR) both at Para-D and Mid-T levels. Both VoStrain and SUVR increased along the gravitational axis with an increment described by statistically different regression lines between VILI and healthy controls and reaching the peak in the dependent regions of the lung (for strain in VILI vs. control was at Para-D: 760 ± 210 vs. 449 ± 106; at Mid-T level 497 ± 373 vs. 193 ± 160; for SUVR, in VILI vs. control was at Para-D: 2.2 ± 1.3 vs. 1.3 ± 0.1; at Mid-T level 1.3 ± 1.0 vs. 0.6 ± 0.03). LMI in both Para-D and Mid-T was statistically significantly higher in VILI than in controls. Conclusions: In this porcine model of VILI, we found a topographical correlation between lung strain and [68Ga]Ga-DOTA-TATE uptake at voxel level, suggesting that mechanical alteration and specific activation of inflammatory cells are strongly linked in VILI. This study represents the first voxel-by-voxel examination of this relationship in a multi-modal imaging analysis. [ABSTRACT FROM AUTHOR]

Increasing seawater influence in coastal areas is an ongoing environmental issue. Gardening is a widespread activity mainly in touristic areas such as the Mediterranean coasts. However, the use of exotic species well adapted to salinity encompasses the risk of invasive species introduction. This study aimed to evaluate salinity tolerance of native geophytes, Pancratium maritimum L. and Eryngium maritimum L., to assess their use as ornamental species in salt affected coastal areas. Experiments were conducted using cultivated plants for flowering response and physiological and enzymatic antioxidant response. Six treatments were applied for two months, exposing plants to seawater (SW) dilutions (Tap-Water, 6.25%SW, 12.5%SW, 25%SW, 50%SW and 100%SW). Taxa decreased inflorescence production being this effect more architectonical in E. maritimum and affecting all inflorescence integrity in P. maritimum. Flowering time was strongly delayed and reduced in P. maritimum, while E. maritimum showed smaller effects among treatments. Physiological and biochemical response showed at moderate salinity levels (1/4SW) variation concomitant with late stress response and senescence in P. maritimum, with decreased water use efficiency, NPQ values, and enzymatic activity, and increased malondialdehyde (MDA) levels. In contrast, E. maritimum showed early stress response with steady gas exchange response, increasing NPQ values and catalase (CAT) and superoxide dimutase (SOD) activity, and decreasing MDA levels with salinity. Glutathione enzymes showed limited participation in both species. The results of this study suggest that neither species can be classified as halophytes, but they exhibit tolerance to low and moderate salinity levels, making them suitable for ornamental use. [ABSTRACT FROM AUTHOR]

Apalutamide is a selective androgen receptor signalling inhibitor that is used in the treatment of prostate cancer. Skin rash is one of the most common adverse events with apalutamide. Although the majority of rash events are grade 1 and 2, the appearance of skin rash during treatment can lead to dose reduction, a pause in treatment or even treatment discontinuation, especially if patients present late when the rash has become severe. This in turn can result in a significant delay or even a permanent discontinuation in the patient's treatment of prostate cancer. As apalutamide is a generally well tolerated and an effective treatment for many men with advanced prostate cancer, it is extremely important to make attempts to prevent skin problems or to manage them at the earliest stage possible. We therefore have developed practical guidance for the management of apalutamide-related rash, including an infographic with recommendations for rash management by grade. Central to this approach is patient education and awareness. Encouraging patients to proactively care for their skin from the start of treatment and informing them of the risk of rash with apalutamide therapy are essential. If the patient observes any skin changes, they should be advised to report it straight away to their cancer care team. Adopting this simple, proactive approach of patient education and increased vigilance from the care team is expected to lead to early identification of rash and subsequent intervention to allow for quicker resolution and enable patients to continue their cancer treatment with a drug that can delay disease progression and increase survival in patients with prostate cancer. [ABSTRACT FROM AUTHOR]

Purpose: This study investigates the potential of inflammatory parameters (IP), symptoms, and patient-related outcome measurements as biomarkers of severity and their ability to predict tuberculosis (TB) evolution. Methods: People with TB were included prospectively in the Stage-TB study conducted at five clinical sites in Barcelona (Spain) between April 2018 and December 2021. Data on demographics, epidemiology, clinical features, microbiology, and Sanit George Respiratory Questionnaire (SGRQ) and Kessler-10 as Health-Related Quality of Life (HRQoL) were collected at three time points during treatment. C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), neutrophil/lymphocyte, and monocyte/lymphocyte ratios (NLR and MLR), complement factors C3, C4, and cH50, clinical and microbiological data, and HRQoL questionnaires were assessed at baseline, 2 months, and 6 months. Their ability to predict sputum culture conversion (SCC) and symptom presence after 2 months of treatment was also analysed. Results: The study included 81 adults and 13 children with TB. The CRP, ESR, NLR, and MLR values, as well as the presence of symptoms, decreased significantly over time in both groups. Higher IP levels at baseline were associated with greater bacillary load and persistent symptoms. Clinical severity at baseline predicted a delayed SCC. Kessler-10 improved during follow-up, but self-reported lung impairment (SGRQ) persisted in all individuals after 6 months. Conclusions: IP levels may indicate disease severity, and sustained high levels are linked to lower treatment efficacy. Baseline clinical severity is the best predictor of SCC. Implementing health strategies to evaluate lung function and mental health throughout the disease process may be crucial for individuals with TB. [ABSTRACT FROM AUTHOR]

Respiratory syncytial virus (RSV) causes most of the cases of bronchiolitis and thousands of deaths annually, particularly in infants less than 6 months old. In Catalonia (Spain), infants born between April 2023 and March 2024 aged 0–6 months during their first RSV season have been candidates to receive nirsevimab, the novel monoclonal antibody against RSV, since October 2023. We aimed to analyse the dynamics of all-causes bronchiolitis diagnoses and RSV community infections in the current season and compare them to pre-nirsevimab epidemics. We collected epidemiological data from the Information System for Surveillance of Infections in Catalonia (SIVIC) on daily all-causes bronchiolitis clinical diagnoses and RSV-confirmed cases provided by rapid antigen tests in primary care practices. We calculated the rate ratio (RR) for the incidence of all-causes bronchiolitis for children aged 0-11 m-old with respect to 12-35 m-old between September 2014 and January 2024. We analysed the RR of the incidence of RSV-confirmed infection for 0-11 m-old and 12-35 m-old with respect to the > 35 m-old, from January 2021 to January 2024. We then computed the relative difference of the RR, designated as percentage of reduction of risk, between season 2023/2024 and former epidemics. With a global coverage recorded rate for nirsevimab of 82.2% in January 2024, the age-specific 0-11 m-old RR (95% CI) of RSV infection incidence for > 35 m-old was 1.7 (1.5–2.0) in season 2023/2024. The RR (95% CI) had been 7.4 (5.6–9.9), 8.8 (6.9–11.3), and 7.1 (5.7–8.9) in 2020/2021, 2021/2022, and 2022/2023, respectively. Regarding the incidence of all-causes bronchiolitis for the 0-11 m-old group compared to the 12-35 m-old, the pre-pandemic (2014/2015–2019/2020) and 2022/2023 RR (95% CI) were 9.4 (9.2–9.6) and 6.0 (5.7–6.2), respectively, significantly higher than the RR of 3.6 (3.4–3.8) for the most recent season, 2023/2024. Conclusion: Concurring with the introduction of nirsevimab, the risk of RSV infection for infants aged 0-11 m-old compared to > 35 m-old has been reduced by 75.6% (73.4–77.5) in last season, and the risk for all-causes bronchiolitis for 12-35 m-old by 61.9% (60.9–62.9) from the pre-pandemic period and by 39.8% (39.3–40.2) from the 2022/2023 epidemic, despite high RSV community transmission, especially in older infants What is Known: • RSV is responsible for approximately 70% of bronchiolitis cases and causes severe disease, particularly in infants < 6 months of age. • Nirsevimab effectiveness against RSV-associated disease, particularly hospitalisations, was expected to be around 80%; other Spanish regions, such as Galicia and Valencia, and European countries including Luxembourg and Germany, have already reported good results in implementing nirsevimab to prevent RSV-associated hospitalisations and PICU stays. What is New: • We provide insight into the community incidence of RSV and all-causes bronchiolitis for season 2023/2024, when nirsevimab has been introduced to the Catalan population, using. primary healthcare data, which enabled us to assess the burden of RSV infections and bronchiolitis in the commonly seasonally saturated primary healthcare practices. • Our study reveals that the risk of all-causes bronchiolitis for infants aged 0-11 m-old compared to older infants was reduced by 40% compared to the previous season and 62% compared to pre-pandemic standards, and for RSV infection it was reduced by 76%. [ABSTRACT FROM AUTHOR]

Phase retrieval methods used in computer generated holograms such as Gerchberg-Saxton and gradient descent give results which are prone to noise and other defects. This work builds up on the idea of time-averaging multiple hologram frames, first introduced in methods like One-Step Phase-Retrieval and Adaptive One-Step Phase-Retrieval. The proposed technique called Multi-Frame Holograms Batched Optimization uses the L-BFGS optimization algorithm to simultaneously generate a batch of binary phase holograms which result in an average reconstructed image of improved fidelity and fast algorithmic convergence, both in the Fraunhoffer and the Fresnel regimes. The results are compared to One-Step Phase-Retrieval and Adaptive One-Step Phase-Retrieval in simulation and experimentally, proving the superiority of the proposed approach. This technique can be easily extended to other spatial modulation methods. [ABSTRACT FROM AUTHOR]

To explore preoperative and operative risk factors for red blood cell (RBC) transfusion requirements during liver transplantation (LT) and up to 24 h afterwards. We evaluated the associations between risk factors and units of RBC transfused in 176 LT patients using a log-binomial regression model. Relative risk was adjusted for age, sex, and the model for end-stage liver disease score (MELD) (adjustment 1) and baseline hemoglobin concentration (adjustment 2). Forty-six patients (26.14%) did not receive transfusion. Grafts from cardiac-death donors were used in 32.61% and 31.54% of non-transfused and transfused patients, respectively. The transfused group required more reoperation for bleeding (P = 0.035), longer mechanical ventilation after LT (P < 0.001), and longer ICU length of stay (P < 0.001). MELD and hemoglobin concentrations determined RBC requirements. For each unit of increase in the MELD score, 2% more RBC units were transfused, and non-transfusion was 0.83-fold less likely. For each 10-g/L higher hemoglobin concentration at baseline, 16% less RBC transfused, and non-transfusion was 1.95-fold more likely. Ascites was associated with 26% more RBC transfusions. With an increase of 2 mm from the baseline in the A10Fibtem measurement of maximum clot firmness, non-transfusion was 1.14-fold more likely. A 10-min longer cold ischemia time was associated with 1% more RBC units transfused, and the presence of post-reperfusion syndrome with 45% more RBC units. We conclude that preoperative correction of anemia should be included in LT. An intervention to prevent severe hypotension and fibrinolysis during graft reperfusion should be explored. Trial register: European Clinical Trials Database (EudraCT 2018–002,510-13) and ClinicalTrials.gov (NCT01539057). [ABSTRACT FROM AUTHOR]

piRNAs are crucial for transposon silencing, germ cell maturation, and fertility in male mice. Here, we report on the genetic landscape of piRNA dysfunction in humans and present 39 infertile men carrying biallelic variants in 14 different piRNA pathway genes, including PIWIL1, GTSF1, GPAT2, MAEL, TDRD1, and DDX4. In some affected men, the testicular phenotypes differ from those of the respective knockout mice and range from complete germ cell loss to the production of a few morphologically abnormal sperm. A reduced number of pachytene piRNAs was detected in the testicular tissue of variant carriers, demonstrating impaired piRNA biogenesis. Furthermore, LINE1 expression in spermatogonia links impaired piRNA biogenesis to transposon de-silencing and serves to classify variants as functionally relevant. These results establish the disrupted piRNA pathway as a major cause of human spermatogenic failure and provide insights into transposon silencing in human male germ cells. piRNAs are small RNA molecules found primarily in the testes of mice and men. Stallmeyer et al. demonstrate that variants in specific genes can disrupt the formation of piRNAs, impairing spermatogenesis and causing human male infertility. [ABSTRACT FROM AUTHOR]

Recently, CNN-based all-in-one image enhancement methods have been proposed to solve multiple image degradation tasks. However, these CNN-based methods usually have two limitations. One limitation is that they usually design a specific encoder for each image enhancement task, lacking of a unified and simple framework. The other limitation is that they can not effectively capture global image degradation information, as use of the CNN-based encoders has a limited local receptive field. In this work, we propose a TransEncoder-based All-in-one Image Enhancement Network (TAENet), with a single encoder and a decoder, for simultaneously handling multiple image enhancement tasks. Specifically, we propose a Transformer-based Encoder (TransEncoder), which introduces instance normalization to transformer for color recovery. The TransEncoder model global degradation information by using the transformer's global self-attention mechanism. Additionally, inspired by the Mie scattering model, we propose a novel depth loss function for perceiving image depth information by minimizing the depth difference between the enhanced image and the ground-truth, thus further improving model performance. Moreover, a novel contrastive loss is introduced to strengthen task-generalization performance by enhancing the model's representation capability. Experiments show that the TAENet outperforms 24 state-of-the-art methods on image dehazing, image deraining, and low-light image enhancement. [ABSTRACT FROM AUTHOR]

Background: Although there is evidence that cognitive behavioral therapy (CBT)-based group interventions can improve quality of life (QoL) in women undergoing treatment for breast cancer (BC) little is known about factors that mediate and moderate these effects. We examined a) the mediating role of benefit finding on QoL changes after a Cognitive Behavioral Stress Management (CBSM) intervention, and b) whether this mediation effect differed based on baseline optimism in the first year following surgery for BC. Methods: We used data from a prior CBSM trial in 240 women with stage 0–3 BC who completed measures of benefit finding (Benefit Finding Scale, BFS), QoL (Functional Assessment of Cancer Treatment, FACT-G), and optimism (Life Orientation Test-Revised) at baseline (2 – 10 weeks post-surgery), 6-months and 12-months after randomization. CBSM-related changes and mediation and moderation effects were assessed using latent growth curve models. Results: We found CBSM increased benefit finding (b = 2.65, p < 0.01), emotional (b = 0.53, p < 0.01), and functional QoL (b = 0.71, p < 0.05) over time. CBSM-related changes in emotional QoL were mediated by increased benefit finding (indirect effect = 0.68, 95% bootstrapped CI: 0.17, 1.56) but only among participants with low to moderate optimism at baseline. Conclusion: CBSM intervention improved emotional QoL over the first year of breast cancer treatment by increasing benefit finding among women who reported low trait optimism suggesting those who will most likely benefit from improving benefit finding during this stressful period. [ABSTRACT FROM AUTHOR]

Foam cells in atheroma are engorged with lipid droplets (LDs) that contain esters of regulatory lipids whose metabolism remains poorly understood. LD-associated hydrolase (LDAH) has a lipase structure and high affinity for LDs of foam cells. Using knockout and transgenic mice of both sexes, here we show that LDAH inhibits atherosclerosis development and promotes stable lesion architectures. Broad and targeted lipidomic analyzes of primary macrophages and comparative lipid profiling of atheroma identified a broad impact of LDAH on esterified sterols, including natural liver X receptor (LXR) sterol ligands. Transcriptomic analyzes coupled with rescue experiments show that LDAH modulates the expression of prototypical LXR targets and leads macrophages to a less inflammatory phenotype with a profibrotic gene signature. These studies underscore the role of LDs as reservoirs and metabolic hubs of bioactive lipids, and suggest that LDAH favorably modulates macrophage activation and protects against atherosclerosis via lipolytic mobilization of regulatory sterols. The mechanisms and consequences of bioactive lipids release from lipid droplets remain poorly understood. Here the authors link a lipid droplet enzyme to mobilization of esters of regulatory sterols in foam cells and protection against atherosclerosis. [ABSTRACT FROM AUTHOR]

Motivated by recent investigations of Sophie Grivaux and Étienne Matheron on the existence of invariant measures in Linear Dynamics, we introduce the concept of locally bounded orbit for a continuous linear operator T : X ⟶ X acting on a Fréchet space X, and we use this new notion to construct (non-trivial) T-invariant probability Borel measures on (X , B (X)) . [ABSTRACT FROM AUTHOR]

The rationale of this study was to evaluate the efficacy of Dog-assisted Therapy (DAT) in children and adolescents with Fetal Alcohol Spectrum Disorder (FASD). We conducted a randomized controlled trial in a cohort of 71 children and adolescents with FASD. Participants were randomly assigned either to DAT group (n = 38) or Relaxation Group (control group) (n = 33). Results revealed that participants who were assigned to the DAT group experienced significantly reduced externalizing symptoms (CBCL Externalizing Inattention: t (69) = 2.81, p =.007; d = 0.7); CBCL Opposition: t (69) = 2.54, p =.013; d = 0.6), reduced internalizing symptoms (CBCL Social problems: t (69) = 3.21, p =.002; d = 0.8) as well as improvements on social skills (SSIS-P Problem behavior: t (68) = 2.55, p =.013; d = 0.6), and quality of life (KidScreen Autonomy and Parents: t (51) = − 2.03, p =.047; d = 0.5) compared to the relaxation control group. The relaxation control group obtained significant differences between the pre- and post-treatment evaluation, diminishing withdraw symptoms (t (32) = 3.03, p =.005; d = 0.2). Results suggest that DAT and relaxation may be promising adjunctive treatments for children and adolescents with FASD. Clinical trial registration information:http://clinicaltrials.gov/; NCT04038164. [ABSTRACT FROM AUTHOR]

Social capital theorists posit that association members are key agents for propagating norms of trust and trustworthiness from within associations toward the society as a whole. Nevertheless, others claim that social capital is primarily bonding, that is, it helps ingroup members better achieve internal goals, but little benefits or even costs carry over to the rest of society. We deploy experimental methods to probe into whether social capital in associations has a predominantly bridging or bonding nature. We compare members' behavior in anonymous Trust Games with behavior by a demographically comparable sample of non-members. We find that (a) Members are significantly more trusting and trustworthy than the general population both when interacting with fellow members and with people from the general population; (b) Members trust and repay trust from people from the general public nearly at the same level as they do with fellow members. Therefore, most of social capital existing within associations "bridges" over to the rest of society. We quantify 83% of additional trust, and 71% of additional trustworthiness existing in associations vis-à-vis society at large to be bridging and the remainder to be bonding. (c) Association members are no more optimistic or less accurate in predicting others' behavior than people from the general public. (d) Increased involvement in association activities is not correlated with increased pro-sociality. [ABSTRACT FROM AUTHOR]

Background: Familism, the cultural value that emphasizes feelings of loyalty and dedication to one's family, has been related to both positive and negative outcomes in Hispanic cancer survivors. One potential source of observed inconsistencies may be limited attention to the family environment, as familism may be protective in a cohesive family whereas it can exacerbate distress in a conflictive family. Purpose: The current study explored the associations of familism with general and disease-specific health-related quality of life (HRQoL) in Hispanic men who completed prostate cancer (PC) treatment, and whether family cohesion may help explain these relationships. Methods: Hispanic men treated for localized PC (e.g., radiation, surgery) were enrolled in a randomized controlled stress management trial and assessed prior to randomization. Familism (familial obligation) was assessed using Sabogal's Familism Scale and family cohesion was measured using the Family Environment Scale (ranging from high to low). The sexual, urinary incontinence, and urinary obstructive/irritative domains of the Expanded Prostate Cancer Index Composite – Short Form measured disease-specific HRQoL. The physical, emotional, and functional well-being subscales of the Functional Assessment of Cancer Therapy – General captured general HRQoL. Hierarchical linear regression and the SPSS PROCESS macro were used to conduct moderation analyses, while controlling for relevant covariates. Results: Participants were 202 older men on average 65.7 years of age (SD = 8.0) who had been diagnosed with PC an average of 22 months prior to enrollment. Familism was not directly associated with general and disease-specific HRQoL. Moderation analyses revealed that greater familism was related to poorer urinary functioning in the incontinence (p =.03) and irritative/obstructive domains (p =.01), and lower emotional well-being (p =.02), particularly when family cohesion was low. Conclusions: These findings underscore the importance of considering contextual factors, such as family cohesion, in understanding the influence of familism on general and disease-specific HRQoL among Hispanic PC patients. The combined influence of familism and family cohesion predicts clinically meaningful differences in urinary functioning and emotional well-being during the posttreatment phase. Culturally sensitive psychosocial interventions to boost family cohesion and leverage the positive impact of familistic attitudes are needed to enhance HRQoL outcomes in this population. [ABSTRACT FROM AUTHOR]

The article focuses on evaluating real-world outcomes in psoriasis treatment when switching to interleukin-23 inhibitors (IL-23i) after ineffectiveness of ustekinumab. It explores drug survival (DS) and effectiveness of IL-23i in patients who previously discontinued ustekinumab due to ineffectiveness compared to those who had not used ustekinumab before. It uses data from the BioCAPTURE registry to analyze outcomes such as Psoriasis Area and Severity Index (PASI) scores and DS rates.

A trendsetting direct competitive-based biosensing tool has been developed and implemented for the determination of the polyunsaturated fatty acid arachidonic acid (ARA), a highly significant biological regulator with decisive roles in viral infections. The designed methodology involves a competitive reaction between the target endogenous ARA and a biotin-ARA competitor for the recognition sites of anti-ARA antibodies covalently attached to the surface of carboxylic acid-coated magnetic microbeads (HOOC-MµBs), followed by the enzymatic label of the biotin-ARA residues with streptavidin-horseradish peroxidase (Strep-HRP) conjugate. The resulting bioconjugates were magnetically trapped onto the sensing surface of disposable screen-printed carbon transducers (SPCEs) to monitor the extent of the biorecognition reaction through amperometry. The operational functioning of the exhaustively optimized and characterized immunosensing bioplatform was highly convenient for the quantitative determination of ARA in serum samples from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2-) and respiratory syncytial virus (RSV)-infected individuals in a rapid, affordable, trustful, and sensitive manner. [ABSTRACT FROM AUTHOR]

Cu/ZnO/CeO2 nanocomposite was supported on metal organic framework (MOF-5) to enhance active sites dispersion and control the nanoparticles agglomeration during synthesis through strong metal-support interactions. The incorporation of MOF-5 alleviated the obstacle facing the commercial ternary Cu/ZnO/Al2O3 regarding low surface area due to nanoparticles agglomeration. In addition, Cu/ZnO/CeO2@MOF-5 gave higher methanol selectivity than the commercial catalyst which can be accounted for by the interfacial sites generated between MOF-5 and Cu/ZnO which favour methanol synthesis over carbon monoxide through regulating the intermediates bonding energies. CeO2 as support for Cu/ZnO nanoparticles was also compared with commercial support and showed to have led to smaller particle size and superior dispersion of Cu active sites as well. Cu/ZnO/CeO2@MOF-5 resulted in methanol STY of 23.3 mg gcat h−1 and selectivity of 79% at mild reaction temperature (260 °C) and pressure (10 bar). Two different MOFs including cerium based MOF and ZIF-8 demonstrated inferior performance compared to MOF-5. [ABSTRACT FROM AUTHOR]

The paper presents a review of the literature and authors’ research on the current achievements in the field of extrusion of aluminium alloys, magnesium alloys, powders and aluminium-based composites in particular. The microstructure transformations taking place during homogenisation of billets from the medium- and high-strength heat-treatable aluminium alloys are still an object of interest of researchers. The recently published papers are related to dissolution of soluble phases formed during solidification and elimination of microsegregation, precipitation of the dispersoids, insoluble phases’ transformation as well as particles re-precipitation during cooling. The novelties in the extrusion of magnesium alloys and aluminium-based composites are shortly reported. Specifics of the extrusion dies design and their working conditions, which limit the products quality and working life of the tools, are extensively reported. The computer-aided designing (CAD) and finite-element method (FEM) and 3D optical scanning were used in analysis aimed at dimensional deviations of the dies and the extruded products. The surface engineering techniques such as welding techniques, diffusion layers and protective coatings such as produced by physical vapour deposition (PVD), plasma-enhanced physical vapour deposition (PAPVD), chemical vapour deposition (CVD) and plasma-enhanced chemical vapour deposition (PECVD) are described. Various original methods of extrusion including the severe plastic deformation processes (SPD), such as cyclic extrusion compression (CEC), equal-channel angular pressing (ECAP) and hydrostatic extrusion (HE) are discussed. The above techniques as well as the new KOBO extrusion process with oscillating die movement generate significant refining of the microstructure of metals and alloys and enable consolidation of the powdered materials. The application of the rapid solidification process connected with the hot extrusion permits production of beneficial microstructure and above-standard mechanical properties of the extruded products. Finally, the opportunities and directions of development of the extrusion process of metals and alloys are indicated. [ABSTRACT FROM AUTHOR]

Coleus scutellarioides (L.) Benth. is a popular species in the world, known for its characteristic magnificent colourful leaves. The study has revealed that the contents of rosmarinic acid and caffeic acid are significantly higher in the plant tissues cultivated in vivo than when under in vitro conditions. The performed qualitative and quantitative analyses confirmed the presence (whose averaged content) of salvinorin A (6.65 µg/1 g of fresh plant) and salvinorin B (50.46 µg/1 g of fresh plant) in tissues of Coleus scutellarioides (L.) Benth. of 'Electric lime' variety. The greatest quantities of these compounds were recorded for plants cultivated in vitro on the MS medium enriched with NAA (naphthyl-1-acetic acid) at a concentration of 0.5 mg∙ dm–3. The research detected differences in the amounts of compounds between plants grown in vivo and those cultivated in vitro. Addition of plant growth regulators into the breeding medium under in vitro conditions was found affecting the amounts of compounds in plant tissues. [ABSTRACT FROM AUTHOR]

We address the issue of detecting hidden periodicity when the signal exhibits periodic correlation, but is additionally affected by non-Gaussian noise with unknown characteristics. This scenario is common in various applications. The conventional approach for identifying periodically correlated (PC) behavior involves the frequency domain-based analysis. In our investigation, we also employ such an approach; however, we use a robust version of the discrete Fourier transform incorporating the Huber function-based M-estimation, unlike the classical algorithm. Building upon this approach, we propose robust coherent and incoherent statistics originally designed to identify hidden periodicity in pure PC models. The novelty of this paper lies in introducing robust coherent and incoherent statistics through the application of the robust discrete Fourier transform in classical algorithms and proposing a new technique for period estimation based on the proposed methodology. We explore two types of PC models and two types of additive noise, resulting in PC signals disturbed by non-Gaussian additive noise. Detecting hidden periodicity in such cases proves to be significantly more challenging than in classical scenarios. Through Monte Carlo simulations, we demonstrate the effectiveness of the proposed robust approaches and their superiority over classical. To further substantiate our findings, we analyze three datasets in which hidden periodicity had previously been confirmed in the literature. Among them, two datasets correspond to the condition monitoring area, being a main motivation of our research. [ABSTRACT FROM AUTHOR]

Background: In preclinical studies, the positron emission tomography (PET) imaging with [11C]UCB-A provided promising results for imaging synaptic vesicle protein 2A (SV2A) as a proxy for synaptic density. This paper reports the first-in-human [11C]UCB-A PET study to characterise its kinetics in healthy subjects and further evaluate SV2A-specific binding. Results: Twelve healthy subjects underwent 90-min baseline [11C]UCB-A scans with PET/MRI, with two subjects participating in an additional blocking scan with the same scanning procedure after a single dose of levetiracetam (1500 mg). Our results indicated abundant [11C]UCB-A brain uptake across all cortical regions, with slow elimination. Kinetic modelling of [11C]UCB-A PET using various compartment models suggested that the irreversible two-tissue compartment model best describes the kinetics of the radioactive tracer. Accordingly, the Patlak graphical analysis was used to simplify the analysis. The estimated SV2A occupancy determined by the Lassen plot was around 66%. Significant specific binding at baseline and comparable binding reduction as grey matter precludes the use of centrum semiovale as reference tissue. Conclusions: [11C]UCB-A PET imaging enables quantifying SV2A in vivo. However, its slow kinetics require a long scan duration, which is impractical with the short half-life of carbon-11. Consequently, the slow kinetics and complicated quantification methods may restrict its use in humans. [ABSTRACT FROM AUTHOR]

We continue our work on the light-front formulation of quarkonium γ∗γ transition form factors, extending the formalism to JPC = 2++ tensor meson states. We present an analysis of γ∗γ → χc2 transition amplitude and the pertinent helicity form factors. Our relativistic formalism is based on the light-front quark-antiquark wave function of the quarkonium. We calculate the two-photon decay width as well as three independent γ∗γ transition form factors for Jz = 0, 1, 2 as a function of photon virtuality Q2. We compare our results for the two-photon decay width to the recently measured ones by the Belle and BES III collaborations. Even when including relativistic corrections, a very small Γ(λ = 0)/Γ(λ = 2) ~ 10−3 ratio is found which is beyond present experimental precision. We also present the form factors as a function of photon virtuality and compare them to the sparse experimental data on the so-called off-shell width. The formalism presented here can be used for other 2++ mesons, excited charmonia or bottomonia or even light q q ¯ -mesons. [ABSTRACT FROM AUTHOR]

Background: Variant transthyretin amyloidosis (ATTRv) can cause sensorimotor and autonomic neuropathy. Objective quantification of sudomotor function may be essential for early diagnosis and early initiation of treatment. The aim of this study is to evaluate the diagnostic value of the Sudoscan® in ATTRv. Methods: Electrochemical skin conductance (ESC) was measured in V30M ATTRv patients, asymtomatic V30M carriers and healthy controls. Comparisons between the three groups were made using the Kruskal-Wallis test, and ROC curves were used to estimate the discriminatory power of ESC values between groups. Results: ESC was measured in 52 ATTRv patients, 107 asymptomatic carriers and 40 healthy controls. ESC was significantly lower in ATTRv patients compared to asymptomatic carriers and healthy controls in both feet and hands; median values are as follows: 40 µS, 78 µS and 81 µS, respectively (p < 0.001), and 53 µS, 69 µS and 74 µS, respectively (p < 0.001). ESC in feet < 70.5 µS had a sensitivity of 89.7% and specificity of 84.6% to discriminate asymptomatic carriers from patients with ATTRv. Conclusion: The determination of ESC by Sudoscan® is a rapid, noninvasive and easily reproducible technique capable of discriminating patients with ATTRv from asymptomatic carriers and healthy controls with adequate sensitivity and specificity. [ABSTRACT FROM AUTHOR]

Background: A breast cancer diagnosis is a highly stressful experience that affects patients' mental health. The study's main objective was to compare the level of anticipative anxiety and depression in patients prepared for their first dose of chemotherapy for breast cancer with virtual reality vs. a standard psychoeducational intervention. Methods: The study was single-center, comparative, and randomized and included a group that received four sessions with virtual reality and another that received four sessions of regular psychoeducational intervention based on mindfulness. Results: 133 patients with a mean age of 49 SD 11.6; range 30–82) were included. Both groups showed a decrease in anxiety and depression with the Anxiety and Depression Scale, higher in the experimental group with significant differences. At three months, a more notable decrease in the Emotional Discomfort Detection Scale was observed in the experimental group, with significant differences. The fighting spirit and cognitive avoidance increased assessed with the MINI-MAC coping scale, higher in the experimental group, with significant differences in all evaluations. Conclusion: A psychoeducational intervention protocol using virtual reality can improve anticipatory anxiety, depression, and emotional distress in breast cancer patients who must start chemotherapy. [ABSTRACT FROM AUTHOR]

The blue crab Callinectes sapidus Rathbun, 1896 is native to the western coasts of the Atlantic Ocean and is currently considered an invasive species in the Mediterranean Sea. In this study, we examined the stomach contents of C. sapidus to determine the frequency of occurrence of microplastics (MPs) and microfibers (MFs) in the Balearic Islands archipelago in the western Mediterranean Sea. A total of 120 individuals were collected from six locations between 2017 and 2020. Overall, 65.8% of the individuals had MPs and/or MFs particles with an average of 1.4 ± 1.6 particles ind.−1 of which an average of 1.0 ± 1.3 items ind.−1 were MFs and an average of 0.4 ± 0.8 items ind.−1 were MPs. In terms of type, fragments were the dominant type of MPs and the most common size of items ranged from between 0.5 and 1 mm (40%) followed by 1–5 mm (31%). The most prevalent polymers were low-density polyethylene (39%) and high-density polyethylene (26%). In terms of links to human activities, MP ingestion was positively correlated with an increase in drain pipes, whereas MF ingestion was positively correlated with an increase in sewage pipelines, providing evidence of potential sources and the bioavailability of these particles in various environments. This study confirms the widespread presence of MP and MF particles, even in areas that are currently managed under different protection statuses, in the stomach contents of invasive blue crab species throughout coastal communities. [ABSTRACT FROM AUTHOR]

The mitoribosome translates mitochondrial mRNAs and regulates energy conversion that is a signature of aerobic life forms. We present a 2.2 Å resolution structure of human mitoribosome together with validated mitoribosomal RNA (rRNA) modifications, including aminoacylated CP-tRNAVal. The structure shows how mitoribosomal proteins stabilise binding of mRNA and tRNA helping to align it in the decoding center, whereas the GDP-bound mS29 stabilizes intersubunit communication. Comparison between different states, with respect to tRNA position, allowed us to characterize a non-canonical L1 stalk, and molecular dynamics simulations revealed how it facilitates tRNA transitions in a way that does not require interactions with rRNA. We also report functionally important polyamines that are depleted when cells are subjected to an antibiotic treatment. The structural, biochemical, and computational data illuminate the principal functional components of the translation mechanism in mitochondria and provide a description of the structure and function of the human mitoribosome. [ABSTRACT FROM AUTHOR]

Background: [11C]metomidate, a methyl ester analogue of etomidate, is used for positron emission tomography of adrenocortical cancer, and has been tested in recent clinical trials for lateralization in primary aldosteronism (PA). However, in PA, visualization as well as uptake quantification are hampered by the tracer's rather high non-specific liver uptake, and its overall clinical usefulness is also limited by the short 20-minute half-life of carbon-11. Therefore, we evaluated para-chloro-2-[18F]fluoroethyl-etomidate, [18F]CETO, a fluorine-18 (T1/2=109.8 min) analogue, as a potential new adrenocortical PET tracer. The aim of this study was to assess radiation dosimetry of [18F]CETO. Results: [18F]CETO showed a high uptake in adrenal glands, still increasing at 5 h post injection. Adrenal glands (absorbed dose coefficients 0.100 ± 0.032 mGy/MBq in males and 0.124 ± 0.013 mGy/MBq in females) received the highest absorbed dose. The effective dose coefficient was 20 µSv/MBq. Conclusions: [18F]CETO has a favourable biodistribution in humans for adrenal imaging. The effective dose for a typical clinical PET examination with 200 MBq [18F]CETO is 4 mSv. Trial registration: ClinicalTrials.gov, NCT05361083 Retrospectively registered 29 April 2022. at, URL: https://clinicaltrials.gov/ct2/show/NCT05361083. [ABSTRACT FROM AUTHOR]

This cluster randomised clinical trial carried out in 20 primary care centres in Barcelona was aimed at assessing the effect of a continuous intervention focused on C-reactive protein (CRP) rapid testing and training in enhanced communication skills (ECS) on antibiotic consumption for adults with acute cough due to lower respiratory tract infection (LRTI). The interventions consisted of general practitioners and nurses' use of CRP point-of-care and training in ECS separately and combined, and usual care. The primary outcomes were antibiotic consumption and variation of the quality-adjusted life years during a 6-week follow-up. The difference in the overall antibiotic prescribing between the winter seasons before and after the intervention was calculated. The sample size calculated could not be reached due to the COVID-19 outbreak. A total of 233 patients were recruited. Compared to the usual care group (56.7%) antibiotic consumption among patients assigned to professionals in the ECS group was significantly lower (33.9%, adjusted odds ratio [aOR] 0.38, 95% CI 0.15–0.94, p = 0.037), whereas patients assigned to CRP consumed 43.8% of antibiotics (aOR 0.70, 95% CI 0.29–1.68, p = 0.429) and 38.4% in the combined intervention group (aOR 0.45, 95% CI, 0.17–1.21; p = 0.112). The overall antibiotic prescribing rates in the centres receiving training were lower after the intervention compared to those assigned to usual care, with significant reductions in β-lactam rates. Patient recovery was similar in all groups. Despite the limited power due to the low number of patients included, we observed that continuous training achieved reductions in antibiotic consumption. [ABSTRACT FROM AUTHOR]