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Abstract There are widespread concerns about bias and discriminatory output related to artificial intelligence (AI), which may propagate social biases and disparities. Digital ageism refers to ageism reflected design, development, and implementation of AI systems and technologies and its resultant data. Currently, the prevalence of digital ageism and the sources of AI bias are unknown. A scoping review informed by the Arksey and O’Malley methodology was undertaken to explore age-related bias in AI systems, identify how AI systems encode, produce, or reinforce age-related bias, what is known about digital ageism, and the social, ethical and legal implications of age-related bias. A comprehensive search strategy that included five electronic bases and grey literature sources including legal sources was conducted. A framework of machine learning biases spanning from data to user by Mehrabi et al. is used to present the findings (Mehrabi et al. 2021). The academic search resulted in 7595 articles that were screened according to the inclusion criteria, of which 307 were included for full-text screening, and 49 were included in this review. The grey literature search resulted in 2639 documents screened, of which 235 were included for full text screening, and 25 were found to be relevant to the research questions pertaining to age and AI. As a result, a total of 74 documents were included in this review. The results show that the most common AI applications that intersected with age were age recognition and facial recognition systems. The most frequent machine learning algorithms used were convolutional neural networks and support vector machines. Bias was most frequently introduced in the early ‘data to algorithm’ phase in machine learning and the ‘algorithm to user’ phase specifically with representation bias (n = 33) and evaluation bias (n = 29), respectively (Mehrabi et al. 2021). The review concludes with a discussion of the ethical implications for the field of AI and recommendations for future research.

Abstract Alongside vaccines, antiviral drugs are becoming an integral part of our response to the SARS‐CoV‐2 pandemic. Nirmatrelvir—an orally available inhibitor of the 3‐chymotrypsin‐like cysteine protease—has been shown to reduce the risk of progression to severe COVID‐19. However, the impact of nirmatrelvir treatment on the development of SARS‐CoV‐2‐specific adaptive immune responses is unknown. Here, by using mouse models of SARS‐CoV‐2 infection, we show that nirmatrelvir administration blunts the development of SARS‐CoV‐2‐specific antibody and T cell responses. Accordingly, upon secondary challenge, nirmatrelvir‐treated mice recruited significantly fewer memory T and B cells to the infected lungs and mediastinal lymph nodes, respectively. Together, the data highlight a potential negative impact of nirmatrelvir treatment with important implications for clinical management and might help explain the virological and/or symptomatic relapse after treatment completion reported in some individuals.

The current global scenario presents us with a growing increase in infections caused by fungi, referred to by specialists in the field as a “silent epidemic”, aggravated by the limited pharmacological arsenal and increasing resistance to this therapy. For this reason, drug repositioning and therapeutic compound combinations are promising strategies to mitigate this serious problem. In this context, this study investigates the antifungal activity of the non-toxic, low-cost and widely available cationic polyelectrolyte Poly(diallyldimethylammonium chloride) (PDDA), in combination with different antifungal drugs: systemic (amphotericin B, AMB), topical (clioquinol, CLIO) and oral (nitroxoline, NTX). For each combination, different drug:PDDA ratios were tested and, through the broth microdilution technique, the minimum inhibitory concentration (MIC) of these drugs in the different ratios against clinically important Candida species strains was determined. Overall, PDDA combinations with the studied drugs demonstrated a significant increase in drug activity against most strains, reaching MIC reductions of up to 512 fold for the fluconazole resistant Candida krusei (Pichia kudriavzevii). In particular, the AMB-PDDA combination 1:99 was highly effective against AMB-resistant strains, demonstrating the excellent profile of PDDA as an adjuvant/association in novel antifungal formulations with outdated conventional drugs. [ABSTRACT FROM AUTHOR]

The extracellular matrix (ECM) is a dynamic set of molecules produced by the cellular component of normal and pathological tissues of the embryo and adult. ECM acts as critical regulator in various biological processes such as differentiation, cell proliferation, angiogenesis, and immune control. The most frequent primary brain tumors are gliomas and by far the majority are adult astrocytic tumors (AATs). The prognosis for patients with these neoplasms is poor and the treatments modestly improves survival. In the literature, there is a fair number of studies concerning the composition of the ECM in AATs, while the number of studies relating the composition of the ECM with the immune regulation is smaller. Circulating ECM proteins have emerged as a promising biomarker that reflect the general immune landscape of tumor microenvironment and may represent a useful tool in assessing disease activity. Given the importance it can have for therapeutic and prognostic purposes, the aim of our study is to summarize the biological properties of ECM components and their effects on the tumor microenvironment and to provide an overview of the interactions between major ECM proteins and immune cells in AATs. As the field of immunotherapy in glioma is quickly expanding, we retain that current data together with future studies on ECM organization and functions in glioma will provide important insights into the tuning of immunotherapeutic approaches. [ABSTRACT FROM AUTHOR]

Abstract Vaccination against an airborne pathogen is very effective if it induces also the development of mucosal antibodies that can protect against infection. The mRNA‐based vaccine‐encoding SARS‐CoV‐2 full‐length spike protein (BNT162b2, Pfizer/BioNTech) protects also against infection despite being administered systemically. Here, we show that upon vaccination, cognate IgG molecules are also found in the saliva and are more abundant in SARS‐CoV‐2 previously exposed subjects, paralleling the development of plasma IgG. The antibodies titer declines at 3 months from vaccination. We identified a concentration of specific IgG in the plasma above which the relevant IgG can be detected in the saliva. Regarding IgA antibodies, we found only protease‐susceptible IgA1 antibodies in plasma while they were present at very low levels in the saliva over the course of vaccination of SARS‐CoV‐2‐naïve subjects. Thus, in response to BNT162b2 vaccine, plasma IgG can permeate into mucosal sites and participate in viral protection. It is not clear why IgA1 are detected in low amount, they may be proteolytically cleaved.

The request for novel hyphenated instruments and techniques, capable of affording exhaustive information and results, is a focus continuously watched out. In this context, the present work aimed at the development of an integrated system combining gas chromatographic (GC) separation with mass spectrometry (MS) and (solid deposition) Fourier transform infrared spectroscopy (FTIR) detection. An external transfer line was designed in the lab for the parallel coupling of the two detectors, in such a way to obtain complementary analytical information consisting of an MS spectrum, an IR spectrum and linear retention indices (LRI), within a single analysis. The instrument performance was demonstrated for the analysis of a commercial mixture consisting of 139 hydrocarbons, comprising linear, branched, unsaturated and aromatic compounds. A 100-m poly(dimethylsiloxane) column was employed for the separation, and the outlet flow was split 95:5 between the IR and MS detectors using two uncoated capillaries. The IR spectra were acquired from solid deposits on a zinc selenide disc (−90 °C), over a spot (detector area) of about 0.1 mm2, in the range of 4000–700 cm−1 and at a resolution of 4 cm−1. Final identification of the separated compounds by a library search was achieved by excluding incorrect results, sequentially using a three-filter approach (85% similarity against reference MS and IR library spectra and ±10 LRI unit tolerance). Based on these preliminary results, the GC-MS/sd-FTIR system is a promising tool for the characterization of complex matrix constituents, for which identification is cumbersome, by using only one detection technique. [ABSTRACT FROM AUTHOR]

The discharge of wastewater from the mining industry has a critical ecological impact, potentially endangering both soil and marine ecosystems. Alternatively, recovering pure water and valuable materials from these hypersaline streams through a technologically efficient process, would help reduce the ecological impact of the waste, while providing a viable supply chain for raw materials such as magnesium, potassium and others, considered critical to the economy. In this context, this work aimed to simultaneously recover pure water and mineral salts from mine wastewater by membrane-assisted crystallization (MAC). A prior theoretical study based on thermodynamic parameters attempted to predict salts precipitation at different temperatures. MAC tests were then performed at specific thermal gradients and feed pretreatment conditions, achieving preferential precipitation of solids products of different composition containing large quantities of Ca or Mg/K minerals from the real mine tailing wastewater. The experiments also demonstrated the central impact of heterogeneous nucleation effects. [ABSTRACT FROM AUTHOR]

To develop and validate a novel Comorbidity score for Robotic Surgery (CRS) in predicting severe complications after robot-assisted radical prostatectomy (RARP). Furthermore, we investigated the impact of the surgical platform (Multi-Port – MP vs Single-Port – SP) according to this score. We included 2085 ("development cohort") and 595 ("validation cohort") patients undergoing RARP at two tertiary referral centers between 2014 and March 2024 in a retrospective study. Statistical analyses included validation of the Charlson Comorbidity Index (CCI) to predict 30-day severe complications (Clavien-Dindo ≥ 3a), development and external validation of CRS using calibration plots and decision curve analysis. Lastly, locally weighted scatterplot smoothing (LOWESS) analysis was used to graphically explore the impact of the robotic platform according to novel CRS. CCI exhibited limited predictive ability for severe complications (60% in the validation cohort). In multivariable logistic regression analyses testing the correlation between each condition included in CCI and severe complications, diabetes and myocardial infarction resulted as independent predictors (OR 1.75 [95%CI 1.05–2.82]; OR 1.92 [95%CI 1.26–2.88]) and were subsequently fitted into a multivariable logistic model including age, previous abdominal surgery and obesity (BMI > 30). The resulting predictive model demonstrated superior discrimination and clinical net benefit in predicting severe complications compared to CCI (AUC 64 vs 60%). At LOWESS analysis, SP platform was associated with lower risk of severe complications as CRS increased compared to MP system. The validated CRS showed better accuracy compared to CCI in predicting severe complications after RARP. Additionally, the use of SP robotic platform may reduce the risk of severe complications in highly comorbid patients according to CRS. [ABSTRACT FROM AUTHOR]

In recent years, the glymphatic system has received increasing attention due to its possible implications in biological mechanisms associated with neurodegeneration. In the field of human brain mapping, this led to the development of diffusion tensor image analysis along the perivascular space (DTI-ALPS) index. While this index has been repeatedly used to investigate possible differences between neurodegenerative disorders and healthy controls, a comprehensive evaluation of its stability across multiple measurements and different disorders is still missing. In this study, we perform a Bayesian meta-analysis aiming to assess the consistency of the DTI-ALPS results previously reported for 12 studies on Parkinson's disease and 11 studies on Alzheimer's disease. We also evaluated if the measured value of the DTI-ALPS index can quantitatively inform the diagnostic process, allowing disambiguation between these two disorders. Our results, expressed in terms of Bayes' Factor values, confirmed that the DTI-ALPS index is consistent in measuring the different functioning of the glymphatic system between healthy subjects and patients for both Parkinson's disease (Log10(BF10) = 30) and Alzheimer's disease (Log10(BF10) = 10). Moreover, we showed that the DTI-ALPS can be used to compare these two disorders directly, therefore providing a first proof of concept supporting the reliability of taking into consideration this neuroimaging measurement in the diagnostic process. Our study underscores the potential of the DTI-ALPS index in advancing our understanding of neurodegenerative pathologies and enhancing clinical diagnostics. [ABSTRACT FROM AUTHOR]

The Latin America region has a considerable extent of varied climate conditions: from tropical, subtropical, and warm temperate to temperate. Among the surface territory, different agricultural products are produced, making them an important food source for human consumption. Fungal species commonly colonize those important agricultural products and often contaminate them with mycotoxins that have a major impact on health, welfare, and productivity. Nowadays, special attention is paid to modified mycotoxins, which are those that cannot be detected by conventional analytical methods. However, little data about their natural occurrence in food and feed is available, especially in Latin American countries, where, among all the countries in this region, only a few of them are working on this subject. Thus, the present review summarizes the published information available in order to determine the possible human exposure risk to these toxins. [ABSTRACT FROM AUTHOR]

This paper describes an experimental and numerical activity investigating the effects on the aerodynamics performance of a Formula 1 vehicle rear wing achieved through the mainplane deformation at high speeds. The primary objective was to show and elucidate the ways in which incorporating a flexible wing can improve vehicle performance at high speeds by mitigating aerodynamic loads. In particular, this study was particularly focused on drag reduction. A 1:2 scaled model of a F1 vehicle rear wing equipped with an interchangeable rigid and deformable mainplane was developed and tested in a wind tunnel. Aerodynamic forces were measured with a six-component external balance along with mainplane deformation via a motion tracking system. To gain insights into the physics of the problem, numerical simulations were performed over the rigid and deformed configuration measured by wind tunnel tests. The experimental and numerical results showed how the deformation of the mainplane can reduce the drag and enhance the performance of the rear wing at high velocity. The results of this study indicate the potential effectiveness of mainplane deformation on vehicle aerodynamic performance particularly on straights, where it is more important to maximize speed rather than the aerodynamic loads generated. [ABSTRACT FROM AUTHOR]

Suicide is a significant leading cause of death among young people, particularly those struggling with mental disorders. The present study utilised data from 230 young people (aged 16–18 years) undergoing a transitional care process from Child and Adolescent Mental Health Services to Adult Mental Health Services within the MILESTONE European project (2014–2019), a longitudinal cluster randomised controlled trial. The objectives of this study were to monitor temporal patterns of general health and social functioning over two years, to detect sex differences, and to identify factors associated with Suicidal Thoughts and Behaviours (STB) at the first and last time points. The results demonstrate a decrease in STB over the two-year follow-up period among all participants. Females exhibited a higher prevalence of STB across all time points, whereas males only exhibited STB at the nine-month follow-up. The most influential factors associated with STB were previous suicide attempts and mood disorders at baseline, and mood disorders and relational problems at the end of follow-up. These findings emphasise the importance of monitoring STB and informing young people undergoing a transitional care period about its key risk factors. Moreover, sex differences in STB suggest the need for different preventive strategies for males and females. [ABSTRACT FROM AUTHOR]

Caloric restriction extends healthy lifespan in multiple species1. Intermittent fasting, an alternative form of dietary restriction, is potentially more sustainable in humans, but its effectiveness remains largely unexplored2–8. Identifying the most efficacious forms of dietary restriction is key for developing interventions to improve human health and longevity9. Here we performed an extensive assessment of graded levels of caloric restriction (20% and 40%) and intermittent fasting (1 and 2 days fasting per week) on the health and survival of 960 genetically diverse female mice. We show that caloric restriction and intermittent fasting both resulted in lifespan extension in proportion to the degree of restriction. Lifespan was heritable and genetics had a larger influence on lifespan than dietary restriction. The strongest trait associations with lifespan included retention of body weight through periods of handling—an indicator of stress resilience, high lymphocyte proportion, low red blood cell distribution width and high adiposity in late life. Health effects differed between interventions and exhibited inconsistent relationships with lifespan extension. 40% caloric restriction had the strongest lifespan extension effect but led to a loss of lean mass and changes in the immune repertoire that could confer susceptibility to infections. Intermittent fasting did not extend the lifespan of mice with high pre-intervention body weight, and two-day intermittent fasting was associated with disruption of erythroid cell populations. Metabolic responses to dietary restriction, including reduced adiposity and lower fasting glucose, were not associated with increased lifespan, suggesting that dietary restriction does more than just counteract the negative effects of obesity. Our findings indicate that improving health and extending lifespan are not synonymous and raise questions about which end points are the most relevant for evaluating aging interventions in preclinical models and clinical trials.Health effects of dietary restriction are uncoupled from longevity. [ABSTRACT FROM AUTHOR]

Background: Diastasis recti abdominis (DRA) indicates an abnormal separation of the rectus abdominal muscles from the midline, resulting in abdominal bulging. Recent literature shows a correlation between DRA and back pain, stress urinary incontinence. Primary goal of this study is to check the correlation between DRA correction in abdominoplasty and improvement of urinary symptoms. Materials and Methods: This is a prospective study on patients with post-pregnancy rectus diastasis who underwent surgical correction of diastasis through conventional abdominoplasty. All patients were asked to complete the ICIQ-FLUTS questionnaire, which assesses urinary disorders, and the SF-36 questionnaire, aimed at quantifying health-related quality of life. The questionnaires were administered to patients the day before surgery and one year after surgery. Results: The recruited patients (n = 51) were then stratified on the presence or absence of stress urinary incontinence. Of the 39 patients with preoperative incontinence, the average scores of the ICIQ-FLUTS were analyzed. In particular, for the questions relating to stress urinary incontinence a statistically significant difference was reported between the preoperative mean and the 1-year mean for all questions (p value<0.05). As regards quality of life, comparing the average scores of each question of SF-36 there is an improvement in the values of all the variables of the questionnaire. Conclusion: The strength of this study, which distinguishes it from other literature, is that the changes in abdominal pressure post-abdominoplasty which should lead to a worsening of stress incontinence, do not cause it. On the contrary, we have demonstrated the improvement of this symptom after conventional abdominoplasty surgery in most patients. Level of Evidence IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 [ABSTRACT FROM AUTHOR]

Substantial evidence highlights the role of the cerebellum in the pathophysiology of tremor in essential tremor (ET), although its potential involvement in altered movement execution in this condition remains unclear. This study aims to explore potential correlations between the cerebellum and basal ganglia functional connectivity and voluntary movement execution abnormalities in ET, objectively assessed with kinematic techniques. A total of 20 patients diagnosed with ET and 18 healthy subjects were enrolled in this study. Tremor and repetitive finger tapping were recorded using an optoelectronic kinematic system. All participants underwent comprehensive 3T-MRI examinations, including 3D-T1 and blood-oxygen-level dependent (BOLD) sequences during resting state. Morphometric analysis was conducted on the 3D-T1 images, while a seed-based analysis was performed to investigate the resting-state functional connectivity (rsFC) of dorsal and ventral portions of the dentate nucleus and the external and internal segments of the globus pallidus. Finally, potential correlations between rsFC alterations in patients and clinical as well as kinematic scores were assessed. Finger tapping movements were slower in ET than in healthy subjects. Compared to healthy subjects, patients with ET exhibited altered FC of both dentate and globus pallidus with cerebellar, basal ganglia, and cortical areas. Interestingly, both dentate and pallidal FC exhibited positive correlations with movement velocity in patients, differently from that we observed in healthy subjects, indicating the higher the FC, the faster the finger tapping. The findings of this study indicate the possible role of both cerebellum and basal ganglia in the pathophysiology of altered voluntary movement execution in patients with ET. [ABSTRACT FROM AUTHOR]

Introduction: Prostate-specific membrane antigen radioguided surgery (PSMA-RGS) might identify lymph node invasion (LNI) in prostate cancer (PCa) patients undergoing extended pelvic lymph node dissection (ePLND). The optimal target-to-background (TtB) ratio to define RGS positivity is still unknown. Materials & methods: Ad interim analyses which focused on 30 patients with available pathological information were conducted. All patients underwent preoperative PSMA positron emission tomography (PET). 99m-Technetium-PSMA imaging and surgery ([99mTc]Tc-PSMA-I&S) was administered the day before surgery. In vivo measurements were conducted using an intraoperative gamma probe. Performance characteristics and implications associated with different TtB ratios were assessed. Results: Overall, 9 (30%) patients had LNI, with 22 (13%) and 80 (11%) positive regions and lymph nodes, respectively. PSMA-RGS showed uptakes in 12 (40%) vs. 7 (23%) vs. 6 (20%) patients for a TtB ratio ≥ 2 vs. ≥ 3 vs. ≥ 4. At a per-region level, sensitivity, specificity and accuracy for a TtB ratio ≥ 2 vs. ≥ 3 vs. ≥ 4 were 72%, 88% and 87% vs. 54%, 98% and 92% vs. 36%, 99% and 91%. Performing ePLND only in patients with suspicious spots at PSMA PET (n = 7) would have spared 77% ePLNDs at the cost of missing 13% (n = 3) pN1 patients. A TtB ratio ≥ 2 at RGS identified 8 (24%) suspicious areas not detected by PSMA PET, of these 5 (63%) harbored LNI, with one pN1 patient (11%) that would have been missed by PSMA PET. Adoption of a TtB ratio ≥ 2 vs. ≥ 3 vs. ≥ 4, would have allowed to spare 18 (60%) vs. 23 (77%) vs. 24 (80%) ePLNDs missing 2 (11%) vs. 3 (13%) vs. 4 (17%) pN1 patients. Conclusions: PSMA-RGS using a TtB ratio ≥ 2 to identify suspicious nodes, could allow to spare > 50% ePLNDs and would identify additional pN1 patients compared to PSMA PET and higher TtB ratios. [ABSTRACT FROM AUTHOR]

Metal ions such as zinc and copper have been used as alternatives to antibiotics, to improve animal health and growth rates in pig farming. This study aims to determine antibiotic residues and Zn concentration in piglets' livers (n = 56) and kidneys (n = 60); and to examine the correlation between the use of Zn and antibiotics, and resistance to Zn and antibiotics of Escherichia coli isolated from piglets' faeces (n = 60). Samples were collected from randomly selected healthy piglets (n = 60); antibiotic residues were quantified by ultra-high-performance-liquid-chromatography time-of-flight mass spectrometry (UHPLC-ToF–MS); Zn was quantified using flame atomic absorption spectrometry (FAAS); microbiological methods were used for E. coli isolation, antibiotic susceptibility, and Zn minimal inhibitory concentration; and Real-Time PCR was used for gene detection. The presence of antibiotic residues and Zn concentrations in the liver was found to be negatively correlated, whilst no significant difference was observed in the kidney. In E. coli isolated from piglet faeces considered to be susceptible or multi-drug-resistant, no significant difference was found between Zn concentrations in the liver and in the kidney, which appears to indicate that Zn accumulated in the liver and in the kidney does not promote resistance to antibiotics in E. coli. The isolates showed tolerance to Zn which would suggest that antibiotic resistance and phenotypic tolerance to Zn in these isolates are not related. The genes zitB and zntA associated to Zn tolerance, were predominantly found in the more resistant Zn isolates. The findings provide insights on how Zn use in pig production maintains antibiotic resistance and metal tolerance in bacteria, with implications for One Health. [ABSTRACT FROM AUTHOR]

Background: The significance of lymphovascular invasion (LVI) in esophageal adenocarcinoma (EAC) has not yet been described. Potential utility as an adjunct to current staging guidelines remains unknown. Methods: The National Cancer Database was queried from 2006 to 2020. Univariate and multivariable models, Kaplan Meier method, and log-rank test were used. Subgroup analyses by pN stage were conducted. Results: Of 9,689 patients, 23.2% had LVI. LVI was an independent prognostic factor (hazard ratio [HR] 1.401, 95% confidence interval [CI] 1.307–1.502, p < 0.0001) with reduction in median survival to 20.0 months (95% CI 18.9–21.4) from 39.7 months (95% CI 37.8–42.3, p < 0.0001). Multivariable survival analysis adjusted on pN and pT stage found that patients with LVI had decreased survival in a given pN stage (p < 0.001). pN0/LVI+ patients had a similar prognosis to the higher staged pN1/LVI− (28.6 months), although pN1/LVI− patients did slightly worse (p = 0.0135). Additionally, patients with pN1/LVI+ had equivalent survival compared with pN2/LVI− (p = 0.178) as did pN2/LVI+ patients compared with pN3/LVI− (p = 0.995). Conclusions: In these data, LVI is an independent negative prognostic factor in EAC. LVI was associated with a survival reduction similar to an upstaged nodal status irrespective of T stage. Patients with LVI may be better classified at a higher pN stage. [ABSTRACT FROM AUTHOR]

Ostracods are small, bivalved crustaceans living in all types of aquatic habitats. All non-marine species belong to the order Podocopida. They usually possess a simple optical system composed of three eyecups called naupliar eye. Phylogenetic data and morphological characteristics support the homology of naupliar eyes between ostracods and other crustacean groups. The photoreceptive system is formed by several specialised cells and can be approximated by a lens-mirror optical apparatus. In some cases, a transparent area of the calcitic carapace can form an additional lens. The visual stimuli are processed by the protocerebrum, possibly via monoaminergic neurons. The presence or absence of one or more specialised cells influence the function of the eyes, and, most likely, their evolution or loss are associated with the adaptation to different habitats. Podocopid ostracods may express long wavelength-sensitive rhabdomeric opsins and may possess nonvisual opsins. The few ethological experiments so far conducted demonstrate that non-marine ostracods might be capable of associative learning when trained with light or specific light wavelengths. This work will provide an overview of what is known and what remains to be further investigated about vision and how light cues affect the behaviour in non-marine ostracods. [ABSTRACT FROM AUTHOR]

Parkinson's is the second most common neurodegenerative disease, affecting nearly 8.5M people and steadily increasing. In this research, Multimodal Deep Learning is investigated for the Prodromal stage detection of Parkinson's Disease (PD), combining different 3D architectures with the novel Excitation Network (EN) and supported by Explainable Artificial Intelligence (XAI) techniques. Utilizing data from the Parkinson's Progression Markers Initiative, this study introduces a joint co-learning approach for multimodal fusion, enabling end-to-end training of deep neural networks and facilitating the learning of complementary information from both imaging and clinical modalities. DenseNet with EN outperformed other models, showing a substantial increase in accuracy when supplemented with clinical data. XAI methods, such as Integrated Gradients for ResNet and DenseNet, and Attention Heatmaps for Vision Transformer (ViT), revealed that DenseNet focused on brain regions believed to be critical to prodromal pathophysiology, including the right temporal and left pre-frontal areas. Similarly, ViT highlighted the lateral ventricles associated with cognitive decline, indicating their potential in the Prodromal stage. These findings underscore the potential of these regions as early-stage PD biomarkers and showcase the proposed framework's efficacy in predicting subtypes of PD and aiding in early diagnosis, paving the way for innovative diagnostic tools and precision medicine. [ABSTRACT FROM AUTHOR]

Despite the increasing demand for efficient and sustainable chemical processes, the development of scalable systems using biocatalysis for fine chemical production remains a significant challenge. We have developed a scalable flow system using immobilized enzymes to facilitate flavin-dependent biocatalysis, targeting as a proof-of-concept asymmetric alkene reduction. The system integrates a flavin-dependent Old Yellow Enzyme (OYE) and a soluble hydrogenase to enable H2-driven regeneration of the OYE cofactor FMNH2. Molecular hydrogen was produced by water electrolysis using a proton exchange membrane (PEM) electrolyzer and introduced into the flow system via a designed gas membrane addition module at a high diffusion rate. The flow system shows remarkable stability and reusability, consistently achieving >99% conversion of ketoisophorone to levodione. It also demonstrates versatility and selectivity in reducing various cyclic enones and can be extended to further flavin-based biocatalytic approaches and gas-dependent reactions. This electro-driven continuous flow system, therefore, has significant potential for advancing sustainable processes in fine chemical synthesis. Flavin-based biocatalysis using flavin mononucleotide (FMN) cofactor attracts significant attention for its application in asymmetric alkene reduction and various other reactions, however, the scale-up of flavin-based biocatalysis in flow remains unexplored. Here, the authors develop a closed-loop flow platform for H2-driven regeneration of cofactor FMNH2 and ene-reduction using immobilized Old Yellow Enzyme, achieving >99% conversion of ketoisophorone to levodione. [ABSTRACT FROM AUTHOR]

Background: Operators in the obituary and necropsy sectors are exposed to various environmental hazards during specific tasks. Despite this exposure, occupational risks have often been underestimated, resulting in a lack of substantial evidence. The primary objectives of this study were to identify sources of chemical risk, establish procedures for monitoring and quantifying exposure during necropsy activities, and recommend adjustments to regulatory guidelines to protect the health of the operators. The study was conducted at the Legal Medicine Unit of the Umberto I General Hospital in Rome, focusing on the quantitative measurement of particulate matter (PM) exposure among at-risk operators during necropsy activities. Environmental levels of total suspended particles, PM10, PM4, PM2.5, and PM1 were assessed by evaluating the average, minimum, and maximum instantaneous indoor concentrations using an airborne analyzer. Results: The monitoring activities revealed that the PM concentrations were significantly lower than the recognized reference values. However, bone sawing, body removal, and cleaning were identified as high-risk maneuvers for dust suspension. Conclusions: Our study highlighted specific risks associated with necropsy activities, particularly concerning timing and certain maneuvers. These results may lead to interventions for improving current prevention procedures, implementing good practices, and developing specific guidelines to enhance operator safety. [ABSTRACT FROM AUTHOR]

Aristotle and utopia may seem an odd combination. Anthologies of utopian texts do not contain passages from Aristotle's writings. He also typically does not feature in histories of utopia. Nonetheless, a close reading of the Politics reveals that Aristotle had an extensive and rather distinctive interest in the enterprise of imagining utopias or ideal cities. The peculiarity of his exploration of utopia lies in its multifaceted approach. He combines critical assessments of some of his predecessors' ideal cities with the creation of several of his own. This article explores the hypothesis that Aristotle's lengthy and varied analysis of ideal cities plays a crucial, though not obvious, role in the history of utopia. The relevance of his speculation lies in identifying (i) distinct ways of conceptualizing the activity of imagining a utopia and (ii) themes and concerns fundamental to designing it. However, the importance of Aristotle's place in the history of utopia is not primarily due to his direct impact on later utopists – his major influence is limited to a handful of Renaissance authors. Instead, his significance lies predominantly in the fact that he was one of the very first thinkers to recognize and articulate key elements of the utopian endeavour. This study examines the points of contact between Aristotle's utopias and representative modern/contemporary utopias and dystopias. It aims not to institute strict parallelisms between these works and the Politics but to show how they share some of the 'essential ingredients' of utopian literature. [ABSTRACT FROM AUTHOR]

The protection of steel surfaces from wear under extreme pressure conditions is of major importance in several industries as it provides better performance and longer life of machinery. The motivation for this work was to study the lubrication of steel by ionic liquids (ILs), which have recently emerged as greener alternatives to commercial lubricants and additives. Three ILs based on sulfur-containing anions, used as 2-wt% additives in polyethylene glycol base oil (MW 200; PEG 200), were tested in the lubrication of ASTM 52100 bearing steel contacts in extreme pressure conditions (under mixed lubrication with a Hertzian pressure of 1.12 GPa) using a mini traction machine (MTM). Due to the poor resistance to corrosion of bearing steel, a semi-ester of succinic acid derivative corrosion inhibitor (Lanxess RC 4801) was added to the mixtures at a 1 wt% concentration. The ILs 1-hexyl-methylimidazolium trifluoromethanesulfonate ([C6mim][TfO]) and 1-hexyl-4-picolinium trifluoromethanesulfonate ([C6-4-pic][TfO]) revealed promising results in terms of surface protection of bearing steel. In contrast, 4-picolinium hydrogen sulfate ([4-picH][HSO4]) as 2-wt% additive to PEG 200 + 1% RC 4801 did not show any improvement in wear performance compared to neat PEG 200 + 1% RC 4801. PEG 200 + 2% [C6mim][TfO] + 1%RC 4801 allowed for a decrease in wear up to ~ 76% and PEG 200 + 2% [C6-4-pic][TfO] + 1%RC 4801 up to ~ 46% when compared with neat PEG 200 + 1% RC 4801. Optical microscopy images suggest the formation of an adsorbed layer, which was further supported by chemical analysis via x-ray photoelectron spectroscopy (XPS) data for [C6mim][TfO]. [ABSTRACT FROM AUTHOR]

Purpose: A comprehensive review of the literature on the time between the onset of symptoms and the first episode of care and its effects on important worker outcomes in compensated musculoskeletal conditions is currently lacking. This scoping review aimed to summarize the factors associated with time to service and describe outcomes in workers with workers' compensation accepted claims for musculoskeletal conditions. Methods: We used the JBI guidelines for scoping reviews and reported following the PRISMA-ScR protocol. We included peer-reviewed articles published in English that measured the timing of health service initiation. We conducted searches in six databases, including Medline (Ovid), Embase (Ovid), PsycINFO, Cinahl Plus (EBSCOhost), Scopus, and the Web of Science. Peer-reviewed articles published up to November 01, 2022 were included. The evidence was summarized using a narrative synthesis. Results: Out of the 3502 studies identified, 31 were included. Eight studies reported the factors associated with time to service. Male workers, availability of return to work programmes, physically demanding occupations, and greater injury severity were associated with a shorter time to service, whereas female workers, a high number of employees in the workplace, and having legal representation were associated with a longer time to service. The relationship between time service and worker outcomes was observed in 25 studies, with early access to physical therapy and biopsychosocial interventions indicating favourable outcomes. Conversely, early opioids, and MRI in the absence of severe underlying conditions were associated with a longer duration of disability, higher claim costs, and increased healthcare utilization. Conclusion: Existing evidence suggests that the time to service for individuals with compensated musculoskeletal conditions was found to be associated with several characteristics. The relationship between time to service and worker outcomes was consistently indicated in the majority of the studies. This review highlights the need to consider patient-centred treatments and develop strategies to decrease early services with negative effects and increase access to early services with better outcomes. [ABSTRACT FROM AUTHOR]

The death of myocytes occurs through different pathways, but the rupture of the plasma membrane is the key point in the transition from reversible to irreversible injury. In the myocytes, three major groups of structural proteins that link the extracellular and intracellular milieus and confer structural stability to the cell membrane: the dystrophin-associated protein complex, the vinculin–integrin link, and the spectrin-based submembranous cytoskeleton. The objective was to determine if remote ischemic preconditioning (rIPC) preserves membrane-associated cytoskeletal proteins (dystrophin and β-dystroglycan) through the inhibition of metalloproteinase type 2 (MMP-2) activity. A second objective was to describe some of the intracellular signals of the rIPC, that modify mitochondrial function at the early reperfusion. Isolated rat hearts were subjected to 30 min of global ischemia and 120 min of reperfusion (I/R). rIPC was performed by 3 cycles of ischemia/reperfusion in the lower limb (rIPC). rIPC significantly decreased the infarct size, induced Akt/GSK-3 β phosphorylation and inhibition of the MPTP opening. rIPC improved mitochondrial function, increasing membrane potential, ATP production and respiratory control. I/R increased ONOO− production, which activates MMP-2. This enzyme degrades β-dystroglycan and dystrophin and collaborates to sarcolemmal disruption. rIPC attenuates the breakdown of β-dystroglycan and dystrophin through the inhibition of MMP-2 activity. Furthermore, we confirm that rIPC activates different intracellular pathway that involves the an Akt/Gsk3β and MPTP pore with preservation of mitochondrial function. [ABSTRACT FROM AUTHOR]

Salt marshes have ecological and economic value, but shoreline development, the increasing rate of sea-level rise, and other human impacts have caused significant loss of salt marshes. As a result, restoration of these ecosystems is widespread. For restoration and management to be effective, it is imperative to improve our understanding of marsh-building plants that serve as the ecological foundation of these habitats. Given the observed differences in characteristics between populations of smooth cordgrass, Spartina alterniflora, restoration plantings may impact the biodiversity and resilience of restored ecosystems. Understanding differences in the structural and functional outcomes of active planting of restoration sites will enable the long-term success of restoration efforts to be improved. Natural and restored salt marshes in Long Island Sound were studied in 2021–2022 for S. alterniflora genetics, biomass, stem morphology, and faunal community composition. The average genotypic diversity of S. alterniflora was more than 4 times higher in restored than in natural marshes, and differentiation between each restored site and natural sites decreased with time. No difference was observed in live S. alterniflora belowground biomass; however, mean dead belowground biomass in natural marshes was more than 3 times greater than in restored marshes. Marsh platform invertebrates differed between the restored and natural sites, with natural marsh edge habitats having 9 times higher density of Geukensia demissa and 3 times as many crab burrows than in restored marshes, but there was no detected difference in species richness or abundance of nekton at high tide. With restoration practitioners seeking resilient, self-sustaining ecosystems, it is important to evaluate whether restored marsh characteristics are consistent with those goals and modify restoration planning accordingly to incorporate genetics, structure, and function. [ABSTRACT FROM AUTHOR]

Abstract Acute Myeloid Leukemia is one of the most aggressive blood cancers with a high frequency of relapse. While standard chemotherapy is able to target rapidly proliferating immature blasts, it fails to eradicate slowly proliferating Leukemic Stem Cells. Therefore, new therapeutic strategies that efficiently target LSCs are urgently needed. Recent studies suggest that LSCs have particular metabolic vulnerabilities, which would open the possibility of a therapeutic window with limited off‐target effects on the normal hematopoietic system. In this issue of EMBO Molecular Medicine, So and colleagues investigate the mechanism of action of AG636, a new potent inhibitor of de novo pyrimidine synthesis, and discovered an unexpected link to AML protein translation essential for LSC function.

Purpose: To describe the volume, timing and provider of mental health services provided to workers with accepted low back pain (LBP) claims, and to identify determinants of service volume and time to first mental health service. Methods: Using claim and service-level workers' compensation data from four Australian states (Queensland, South Australia, Western Australia, Victoria) for LBP claims with at least one mental health service lodged between 1 July 2011 and 30 June 2015. Mental health services occurring 30 days prior to 730 days following claim acceptance were examined. Outcomes were number of mental health services and time (weeks) from claim acceptance to first service, calculated overall, by provider and interaction type, and by independent variables (age group, sex, time loss duration, financial year of lodgement, jurisdiction, socioeconomic status, remoteness). Negative binomial and Cox regression models examined differences between service volume and time to first service by independent variables, respectively. Results: Of workers with LBP claims who accessed mental health services, psychologist services were most common (used by 91.2% of workers) and 16% of workers saw multiple provider types. Number of services increased with time loss duration, as did time to first service. Victorian workers had the most services, yet accessed them latest. Conclusions: Psychologist services were most common, longer duration claims used more mental health services but accessed them later, and there were a number of jurisdictional differences. Results suggest opportunities for workers' compensation authorities to provide, to those who may benefit, greater and earlier access to mental health care. [ABSTRACT FROM AUTHOR]

Aging is associated with the onset and progression of multiple diseases, which limit health span. Chronic low-grade inflammation in the absence of overt infection is considered the simmering source that triggers age-associated diseases. Failure of many cellular processes during aging is mechanistically linked to inflammation; however, the overall decline in the cellular homeostasis mechanism of autophagy has emerged as one of the top and significant inducers of inflammation during aging, frequently known as inflammaging. Thus, physiological or pharmacological interventions aimed at improving autophagy are considered geroprotective. Rapamycin analogs (rapalogs) are known for their ability to inhibit mTOR and thus regulate autophagy. This study assessed the efficacy of everolimus, a rapalog, in regulating inflammatory cytokine production in T cells from older adults. CD4+ T cells from older adults were treated with a physiological dose of everolimus (0.01 µM), and indices of autophagy and inflammation were assessed to gain a mechanistic understanding of the effect of everolimus on inflammation. Everolimus (Ever) upregulated autophagy and broadly alleviated inflammatory cytokines produced by multiple T cell subsets. Everolimus's ability to alleviate the cytokines produced by Th17 subsets of T cells, such as IL-17A and IL-17F, was dependent on autophagy and antioxidant signaling pathways. Repurposing the antineoplastic drug everolimus for curbing inflammaging is promising, given the drug's ability to restore multiple cellular homeostasis mechanisms. Everolimus inhibits mTORC1 and promotes autophagy in CD4 + T cells from O adults, which induces the activation and translocation of NRF2 to the nucleus. NRF2 induces the production of first-line antioxidant enzymes SOD1, SOD2, and catalase, thus lowering reactive oxygen species and proinflammatory cytokine production [ABSTRACT FROM AUTHOR]

Many conventional statistical and machine learning methods face challenges when applied directly to high dimensional temporal observations. In recent decades, Functional Data Analysis (FDA) has gained widespread popularity as a framework for modeling and analyzing data that are, by their nature, functions in the domain of time. Although supervised classification has been extensively explored in recent decades within the FDA literature, ensemble learning of functional classifiers has only recently emerged as a topic of significant interest. Thus, the latter subject presents unexplored facets and challenges from various statistical perspectives. The focal point of this paper lies in the realm of ensemble learning for functional data and aims to show how different functional data representations can be used to train ensemble members and how base model predictions can be combined through majority voting. The so-called Functional Voting Classifier (FVC) is proposed to demonstrate how different functional representations leading to augmented diversity can increase predictive accuracy. Many real-world datasets from several domains are used to display that the FVC can significantly enhance performance compared to individual models. The framework presented provides a foundation for voting ensembles with functional data and can stimulate a highly encouraging line of research in the FDA context. [ABSTRACT FROM AUTHOR]

The objective of this review is to survey radiomics signatures for detecting pathological extracapsular extension (pECE) on magnetic resonance imaging (MRI) in patients with prostate cancer (PCa) who underwent prostatectomy. Scientific Literature databases were used to search studies published from January 2007 to October 2023. All studies related to PCa MRI staging and using radiomics signatures to detect pECE after prostatectomy were included. Systematic review was performed according to Preferred Reporting Items for Systematic Review and Meta-analyses (PRISMA). The risk of bias and certainty of the evidence was assessed using QUADAS-2 and the radiomics quality score. From 1247 article titles screened, 16 reports were assessed for eligibility, and 11 studies were included in this systematic review. All used a retrospective study design and most of them used 3 T MRI. Only two studies were performed in more than one institution. The highest AUC of a model using only radiomics features was 0.85, for the test validation. The AUC for best model performance (radiomics associated with clinical/semantic features) varied from 0.72–0.92 and 0.69–0.89 for the training and validation group, respectively. Combined models performed better than radiomics signatures alone for detecting ECE. Most of the studies showed a low to medium risk of bias. After thorough analysis, we found no strong evidence supporting the clinical use of radiomics signatures for identifying extracapsular extension (ECE) in pre-surgery PCa patients. Future studies should adopt prospective multicentre approaches using large public datasets and combined models for detecting ECE. Critical relevant statement: The use of radiomics algorithms, with clinical and AI integration, in predicting extracapsular extension, could lead to the development of more accurate predictive models, which could help improve surgical planning and lead to better outcomes for prostate cancer patients. Protocol of systematic review registration: PROSPERO CRD42021272088. Published: https://doi.org/10.1136/bmjopen-2021-052342. Key Points: Radiomics can extract diagnostic features from MRI to enhance prostate cancer diagnosis performance. The combined models performed better than radiomics signatures alone for detecting extracapsular extension. Radiomics are not yet reliable for extracapsular detection in PCa patients. [ABSTRACT FROM AUTHOR]

High-hazard seismic zones can remain silent over centuries with meager seismicity rates challenging our understanding of seismic processes. We focus on the comprehensive analysis of cascading episodes of swarms and seismic sequences following the 2009 L’Aquila mainshock (MW 6.3) in the southern-central Apennine that previously experienced ~ M7 earthquakes. We enhance the seismic catalog, unmasking low-magnitude seismicity down to completeness magnitude ML ~ 0, and we unveil that the microseismicity might be secondarily triggered by the L’Aquila mainshock, influencing the frictional properties in the nearby fault zones or opening fault valves generating the intense seismic activity detected from 2009 to 2013. The diffusivity, observed in the most seismic episodes, and the high Vp/Vs values (> 1.88) indicate fluid circulation promoting multilayered extensional seismicity within 11–15 km and 16–23 km depth ranges. Mapping the 3D distribution of seismicity alongside geological data reveals an evident tectonic influence, unveiling unknown geometric aspects and providing the first evidence of a NNE-dipping deformation zone bounding at depths of 11–15 km the overlying fault system. Deeper seismicity suggests a mantellic CO2 ascending shape. These findings enrich the literature on tectonic seismic swarms in extensional domains, providing essential constraints on fluid involvement in the seismic processes and contributing to forthcoming discussions on the seismotectonic setting in high-seismic-risk areas of the Apennines of Italy. [ABSTRACT FROM AUTHOR]

Coordinate-based meta-analysis (CBMA) is a powerful technique in the field of human brain imaging research. Due to its intense usage, several procedures for data preparation and post hoc analyses have been proposed so far. However, these steps are often performed manually by the researcher, and are therefore potentially prone to error and time-consuming. We hence developed the Coordinate-Based Meta-Analyses Toolbox (CBMAT) to provide a suite of user-friendly and automated MATLAB® functions allowing one to perform all these procedures in a fast, reproducible and reliable way. Besides the description of the code, in the present paper we also provide an annotated example of using CBMAT on a dataset including 34 experiments. CBMAT can therefore substantially improve the way data are handled when performing CBMAs. The code can be downloaded from https://github.com/Jordi-Manuello/CBMAT.git. [ABSTRACT FROM AUTHOR]

Ensemble learning is a strategy commonly used to fuse different base models by creating a model ensemble that is expected more accurate on unseen data than the base models. This study describes a new cyber-threat detection method, called PANACEA, that uses ensemble learning coupled with adversarial training in deep learning, in order to gain accuracy with neural models trained in cybersecurity problems. The selection of the base models is one of the main challenges to handle, in order to train accurate ensembles. This study describes a model ensemble pruning approach based on eXplainable AI (XAI) to increase the ensemble diversity and gain accuracy in ensemble classification. We base on the idea that being able to identify base models that give relevance to different input feature sub-spaces may help in improving the accuracy of an ensemble trained to recognise different signatures of different cyber-attack patterns. To this purpose, we use a global XAI technique to measure the ensemble model diversity with respect to the effect of the input features on the accuracy of the base neural models combined in the ensemble. Experiments carried out on four benchmark cybersecurity datasets (three network intrusion detection datasets and one malware detection dataset) show the beneficial effects of the proposed combination of adversarial training, ensemble learning and XAI on the accuracy of multi-class classifications of cyber-data achieved by the neural model ensemble. [ABSTRACT FROM AUTHOR]

Purpose: Asthma, obstructive sleep apnea (OSA), rhinosinusitis, and esophageal reflux are conditions that may overlap, forming a syndrome known as CORE. Whenever clinical remission of severe asthma (SA) is not achieved, it is essential to investigate the presence of comorbidities, in particular the presence of OSA that may lead to the diagnosis of CORE syndrome. Methods: The study was conducted on naive patients with SA and concomitant rhinosinusitis and esophageal reflux, referred to our institute since 2018. Patients who did not experience clinical remission were investigated for OSA through a home sleep apnea test. Subsequently, for those diagnosed with OSA, continuous positive airway pressure (CPAP) was proposed and was re-evaluated after 12 months. Results: Six patients with CORE syndrome were enrolled. The mean apnea–hypopnea index (AHI) was 33.25 ± 20.13 events/h, oxygen desaturation index (ODI) was 28.95 ± 19.95 events/h, and time in bed with SaO2 < 90% (T90) was 26.40 ± 27.22% for which continuous positive airway pressure (CPAP) treatment was proposed but only 3 out of 6 patients accepted. After 12 months, all CPAP-treated patients manifested a significant reduction in daytime sleepiness (ESS score was 6.33 ± 3.8), an improvement in ACT score (+ 8 (+ 32%), + 9 (+ 36%), and + 14 (+ 56%) points), a discontinuation of oral corticosteroids (OCS), an absence of exacerbations, and an improvement of lung function leading to clinical remission of asthma. Conclusion: Whenever facing SA patients, non-responders to therapy, it is important to suspect the presence of CORE syndrome; in particular, the detection and subsequent treatment of OSA would seem to improve the outcome of such patients. [ABSTRACT FROM AUTHOR]

Purpose: The aim of the study is to identify CT findings that are predictive of recurrence of acute uncomplicated colonic diverticulitis, to better risk-stratify these patients for whom guidelines recommend a conservative outpatient treatment and to determine the appropriate management with an improvement of health costs. Materials and Methods: Over the past year, 33 patients enrolled in an outpatient integrated care pathway (PDTA) for uncomplicated acute diverticulitis with 1-year follow-up period, without recurrence, and 33 patients referred to Emergency Department for a recurrent acute diverticulitis were included. Images of admission CT were reviewed by two radiologists and the imaging features were analyzed and compared with Chi-square and Student t tests. Univariate and multivariate Cox regression models were employed to identify parameters that significantly predicted recurrence in 1-year follow-up period and establish cutoff and recurrence-free rates. The maximally selected rank statistics (MSRS) were used to identify the optimal wall thickening cutoff for the prediction of recurrence. Results: Patients with recurrence showed a greater mean parietal thickness compared to the group without recurrence (16 mm vs. 11.5 mm; HR 1.25, p < 0.001) and more evidence of grade 4 of peridiverticular inflammation (40% vs. 12%, p = 0.009, HR 3.44). 12-month recurrence-free rates progressively decrease with increasing thickness and inflammation. In multivariate analysis, only parietal thickness maintained its predictive power with an optimal cutpoint > 15 mm that causes a sixfold increased risk of recurrence (HR 6.22; 95% CI, 3.05–12.67; p < 0.001). Beyond thickness and peridiverticular inflammation, predictive value of early recurrence within 90 days from the 1st episode resulted also an Hinchey Ib on admission CT. Conclusions: The maximum wall thickening and the grade of peridiverticular inflammation can be considered as predictive factors of recurrence and may be helpful in selecting patients for a tailored treatment to prevent the risk of recurrence. [ABSTRACT FROM AUTHOR]

We consider time-dependent perturbations of integrable and near-integrable Hamiltonians. Assuming the perturbation decays polynomially fast as time tends to infinity, we prove the existence of biasymptotically quasi-periodic solutions. That is, orbits converging to some quasi-periodic solutions in the future (as ) and the past (as ). Concerning the proof, thanks to the implicit function theorem, we prove the existence of a family of orbits converging to some quasi-periodic solutions in the future and another family of motions converging to some quasi-periodic solutions in the past. Then, we look at the intersection between these two families when . Under suitable hypotheses on the Hamiltonian's regularity and the perturbation's smallness, it is a large set, and each point gives rise to biasymptotically quasi-periodic solutions. [ABSTRACT FROM AUTHOR]

Rationale: The alcohol cue exposure paradigm is a common method for evaluating new treatments for alcohol use disorder (AUD); however, it is unclear if medication-related reductions in cue-induced craving in the human laboratory can predict the clinical success of those medications in reducing alcohol consumption during clinical trials. Objectives: To use a novel meta-analytic approach to test whether medication effect sizes on cue-induced alcohol craving are associated with clinical efficacy in clinical trials. Method: We searched the literature for medications tested for AUD treatment using both the alcohol cue-reactivity paradigm and randomized clinical trials (RCTs). For alcohol cue-reactivity studies, we computed medication effect sizes for cue-induced alcohol craving (k = 36 studies, 15 medications). For RCTs, we calculated medication effect sizes for heavy drinking and abstinence (k = 139 studies, 19 medications). Using medication as the unit of analysis, we applied the Williamson-York bivariate weighted least squares estimation to account for errors in both independent and dependent variables. We also conducted leave-one-out cross validation simulations to examine the predictive utility of cue-craving medication effect sizes on RCT heavy drinking and abstinence endpoints. Results: There was no significant relationship between medication effects on cue-induced alcohol craving in the human laboratory and medication effects on heavy drinking ( β ^ = 0.253, SE = 0.189, p = 0.090) and abstinence ( β ^ = 0.829, SE = 0.747, p = 0.133) in RCTs. Conclusions: The preliminary results of the current study challenge the assumption that alcohol cue-reactivity alone can be used as an early efficacy indicator for AUD pharmacotherapy development. These findings suggest that a wider range of early efficacy indicators and experimental paradigms be considered for Phase II testing of novel compounds. [ABSTRACT FROM AUTHOR]

Background: Subtle parkinsonian signs, i.e., rest tremor and bradykinesia, are considered soft signs for defining essential tremor (ET) plus. Objectives: Our study aimed to further characterize subtle parkinsonian signs in a relatively large sample of ET patients from a clinical and neurophysiological perspective. Methods: We employed clinical scales and kinematic techniques to assess a sample of 82 ET patients. Eighty healthy controls matched for gender and age were also included. The primary focus of our study was to conduct a comparative analysis of ET patients (without any soft signs) and ET-plus patients with rest tremor and/or bradykinesia. Additionally, we investigated the asymmetry and side concordance of these soft signs. Results: In ET-plus patients with parkinsonian soft signs (56.10% of the sample), rest tremor was clinically observed in 41.30% of cases, bradykinesia in 30.43%, and rest tremor plus bradykinesia in 28.26%. Patients with rest tremor had more severe and widespread action tremor than other patients. Furthermore, we observed a positive correlation between the amplitude of action and rest tremor. Most ET-plus patients had an asymmetry of rest tremor and bradykinesia. There was no side concordance between these soft signs, as confirmed through both clinical examination and kinematic evaluation. Conclusions: Rest tremor and bradykinesia are frequently observed in ET and are often asymmetric but not concordant. Our findings provide a better insight into the phenomenology of ET and suggest that the parkinsonian soft signs (rest tremor and bradykinesia) in ET-plus may originate from distinct pathophysiological mechanisms. [ABSTRACT FROM AUTHOR]

Purpose: Single-Port Robot-Assisted Partial Nephrectomy (SP-RAPN) can be performed by transperitoneal and retroperitoneal approaches. However, there is a lack of surgical outcomes for novel Retroperitoneal Low Anterior Access (LAA) in SP-RAPN. The study compared outcomes of the standard approach (SA), considering transperitoneal (TP) and posterior retroperitoneal (RP) access vs LAA in SP-RAPN series. Methods: 102 consecutive patients underwent SP-RAPN between 2019 and 2023 at a tertiary referral robotic center were identified. Baseline characteristics, peri- and post-operative outcomes were collected. Patients were stratified according to surgical approach into standard (RP or TP) vs LAA and, subsequently, RP vs LAA. Multivariable logistic regression analysis was used to test the probability of the same-day discharge adjusting for comorbidity indexes. Results: Overall, 102 consecutive patients were included in this study (68 SA – 26 TP and 42 posterior RP vs 34 LAA). Median age was 60 (IQR 51.5–66) years and median BMI was 31 (IQR 26.3–37.6). No baseline differences were observed. LAA exhibited significantly shorter length of stay (LOS) (median 10 [IQR 8–12] vs 24 [IQR 12–30.2.] hours, p <.0001), reduced post-operative pain (p <.0001) and decreased narcotic use on 0–1 PO Day (p <.001) compared to SA and RP only. Multivariate analysis, adjusting for comorbidities, identified LAA as a strong predictor for Same-Day Discharge. Conclusion: LAA is an effective approach as well as RP and TP, regardless of the renal mass location, whether it is anterior or posterior, upper/mid or lower pole, yielding favorable outcomes in LOS, post-operative pain and decreased narcotics use compared to SA in SP-RAPN. [ABSTRACT FROM AUTHOR]

Amazonia contains the most extensive tropical forests on Earth, but Amazon carbon sinks of atmospheric CO2 are declining, as deforestation and climate-change-associated droughts1–4 threaten to push these forests past a tipping point towards collapse5–8. Forests exhibit complex drought responses, indicating both resilience (photosynthetic greening) and vulnerability (browning and tree mortality), that are difficult to explain by climate variation alone9–17. Here we combine remotely sensed photosynthetic indices with ground-measured tree demography to identify mechanisms underlying drought resilience/vulnerability in different intact forest ecotopes18,19 (defined by water-table depth, soil fertility and texture, and vegetation characteristics). In higher-fertility southern Amazonia, drought response was structured by water-table depth, with resilient greening in shallow-water-table forests (where greater water availability heightened response to excess sunlight), contrasting with vulnerability (browning and excess tree mortality) over deeper water tables. Notably, the resilience of shallow-water-table forest weakened as drought lengthened. By contrast, lower-fertility northern Amazonia, with slower-growing but hardier trees (or, alternatively, tall forests, with deep-rooted water access), supported more-drought-resilient forests independent of water-table depth. This functional biogeography of drought response provides a framework for conservation decisions and improved predictions of heterogeneous forest responses to future climate changes, warning that Amazonia’s most productive forests are also at greatest risk, and that longer/more frequent droughts are undermining multiple ecohydrological strategies and capacities for Amazon forest resilience.Drought response is structured by water-table depth in higher-fertility Southern Amazonia, whereas lower-fertility Northern Amazonia supports more-drought-resilient forests independent of water-table depth. [ABSTRACT FROM AUTHOR]

Purpose: Nondisplaced intracapsular fractures (Garden I/II) are predominantly treated with an internal fixation technique. The purpose of the study is to identify the best rehabilitation protocol after internal fixation with 3 parallel cannulated screws. Methods: All patients operated on from 2016 to 2021 for femoral neck fractures by internal fixation with 3 cannulated screws were enrolled into this prospective study. The population was divided into two groups: Group A (n = 34) who followed a postoperative rehabilitation protocol involving full and immediate loading, and Group B (n = 22) who followed a postoperative rehabilitation protocol involving late full loading (after 30 days). The two groups were compared with each other by mortality rate, postoperative complications and need for re-interventions. Functional outcome and quality of life were assessed at the minimum follow-up of 1 year using the modified Harris Hip Score (HHS) and the Short form health survey (SF-12) questionnaire. Results: Group A showed a lower complication rate (2.9% vs. 18.2%), a lower 1-year mortality rate (5.9% vs. 9.1%), a better perception of mental health status (SF12-MCS 56.2 vs. 51.4, p = 0.03) but a worse perception of one's physical health status (SF12-PCS 48.1 vs. 56.7, p < 0.01). The two groups were also statistically overlapping in terms of the functional outcome achieved after the intervention (HHS was 90.94 in Group A vs. 93.15 in Group B, p = 0.32). Conclusion: Postoperative complications, mortality and revision rate were higher in patients who followed a late-loaded rather than early loaded rehabilitation protocol. Functional outcome at 1-year survival is not significantly different. In nondisplaced intracapsular hip fractures treated with cannulated screws, an immediate full load should be preferred. Query [ABSTRACT FROM AUTHOR]

LiteBIRD is a satellite mission to be launched by JAXA in the early 2030s. It will measure the Cosmic Microwave Background (CMB) primordial B-modes with an unprecedented sensitivity. Microwave radiation will be detected by Transition Edge Sensors (TESs) arrays multiplexed in frequency domain and read by Superconducting QUantum Interference Devices (SQUIDs). The LiteBIRD SQUID Controller Unit (SCU), based on the heritage of the successful design used for the ground-based SPT3G experiment, presents some novel elements that make it suitable for a space-borne application. We compare our first breadboard model with the ground-based, Off-The-Shelf Components (COTS) version, by driving the same SQUID Array Amplifier (SAA) at 4 K, measuring relevant quantities such as noise, gain and bandwidth. We demonstrate that the noise added by our first prototype (including a switching part for redundancy purposes) never exceeds the noise added by the COTS-based electronics board, representing our benchmark. We also present the first noise estimates with the SAA cooled below 1 K, going closer to the conditions expected for LiteBIRD operation. [ABSTRACT FROM AUTHOR]

In this communication, we describe a characterization procedure suitable to extract the most relevant design parameters of a large area absorber TES, designed for Cosmic Microwave Background measurements, very similar to those that will be fabricated for the LSPE/SWIPE balloon-borne experiment. This is a large (8 mm diameter) Au-on-SiN spiderweb designed to collect many modes of the incoming microwave radiation, in the 145–240 GHz range. After obtaining the critical temperature of the Ti/Au TES and its I–V characteristics, we operate it in Negative Electrothermal Feedback (ETF, DC voltage bias) and we record its response after amplification by a SQUID Array Amplifier. Then, in the same conditions, we illuminate the central area of the absorber with a pulsed LED (red visible light), mounted in the cryogenic environment, with pulses short enough to mimic an instantaneous energy deposition. Furthermore, the same LED is driven to produce a slow modulation of the output signal, to explore the bolometric regime of the TES. With this set of measurements we are able to extract its thermal conductance, its natural time constant, and the loop gain associated with the optimal bias point. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the diagnostic accuracy of the Node-RADS score and the utility of apparent diffusion coefficient (ADC) values in predicting metastatic lymph nodes (LNs) involvement in cervical cancer (CC) patients using magnetic resonance imaging (MRI). The applicability of the Node RADS score across three readers with different years of experience in pelvic imaging was also assessed. Material and methods: Among 140 patients, 68 underwent staging MRI, neoadjuvant chemotherapy and radical surgery, forming the study cohort. Node-RADS scores of the main pelvic stations were retrospectively determined to assess LN metastatic likelihood and compared with the histological findings. Mean ADC, relative ADC (rADC), and correct ADC (cADC) values of LNs classified as Node-RADS ≥ 3 were measured and compared with histological reports, considered as gold standard. Results: Sensitivity, specificity, positive and negative predictive values (PPVs and NPVs), and accuracy were calculated for different Node-RADS thresholds. Node RADS ≥ 3 showed a sensitivity of 92.8% and specificity of 72.5%. Node RADS ≥ 4 yielded a sensitivity of 71.4% and specificity of 100%, while Node RADS 5 yielded 42.9% and 100%, respectively. The diagnostic performance of mean ADC, cADC and rADC values from 78 LNs with Node-RADS score ≥ 3 was assessed, with ADC demonstrating the highest area under the curve (AUC 0.820), compared to cADC and rADC values. Conclusion: The Node-RADS score provides a standardized LNs assessment, enhancing diagnostic accuracy in CC patients. Its ease of use and high inter-observer concordance support its clinical utility. ADC measurement of LNs shows promise as an additional tool for optimizing patient diagnostic evaluation. [ABSTRACT FROM AUTHOR]