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This study sought to understand the geographic distribution of three behavioral health clinician (BHC) types in disadvantaged communities in the U.S. across a standardized index of area disadvantage. CMS National Plan and Provider Enumeration System's data were used to identify BHC practice addresses. Addresses were geocoded and mapped to census block groups across Area Disadvantage Index (ADI) scores. Differences in the proportion of BHCs per 100k people in a block group by ADI, clinician type, and rurality were compared. Zero-inflated negative binomial models assessed associations between ADI score with any amount, and expected count, of BHC type in a block group. The sample included 836,780 BHCs (51.5% counselors, 34.5% social workers, 14.0% psychologists). Results indicated there were fewer BHCs in areas of high disadvantage with 351 BHCs in the lowest need versus 267 BHCs in highest need areas, per 100k people. BHC type was differently associated with the rate of clinicians per 100k by ADI and block groups that were both rural and high ADI had the least BHCs located. Findings suggest the maldistribution of BHCs by ADI underscores how some BHCs may be better positioned to meet the needs of vulnerable communities. Increasing access to behavioral health care requires a workforce equitably positioned in high-need areas. Reforms to payment and practice regulations may support BHCs to deliver services in socially disadvantaged neighborhoods. [ABSTRACT FROM AUTHOR]

Intraperitoneal cellular immunotherapy with CAR-redirected lymphocytes is an intriguing approach to target peritoneal carcinomatosis (PC) from ovarian cancer (OC), which is currently evaluated in clinical trials. PC displays a composite structure with floating tumor cells within ascites and solid-like masses invading the peritoneum. Therefore, a comprehensive experimental model is crucial to optimize CAR-cell therapies in such a peculiar environment. Here, we explored the activity of cytokine-induced killer lymphocytes (CIK), redirected by CAR against mesothelin (MSLN-CAR.CIK), within reductionistic 3D models resembling the structural complexity of both liquid and solid components of PC. MSLN-CAR.CIK effectively killed and were functionally efficient against OC targets. In a "floating-like" 3D context with floating OC spheroids, both tumor localization and killing by MSLN-CAR.CIK were significantly boosted by fluid flow. In a "solid-like" context, MSLN-CAR.CIK were recruited through the extracellular matrix on embedded tumor aggregates, with variable kinetics depending on the effector-target distance. Furthermore, MSLN-CAR.CIK penetrated the inner levels of OC spheroids exerting effective tumor killing. Our findings provide currently unknown therapeutically relevant information on intraperitoneal approaches with CAR.CIK, supporting further developments and improvements for clinical studies in the context of locoregional cell therapy approaches for patients with PC from OC. [ABSTRACT FROM AUTHOR]

Acute myeloid leukemia (AML) is an aggressive disease with a high relapse rate. In this study, we map the metabolic profile of CD34+(CD38low/-) AML cells and the extracellular vesicle signatures in circulation from AML patients at diagnosis. CD34+ AML cells display high antioxidant glutathione levels and enhanced mitochondrial functionality, both associated with poor clinical outcomes. Although CD34+ AML cells are highly dependent on glucose oxidation and glycolysis for energy, those from intermediate- and adverse-risk patients reveal increased mitochondrial dependence. Extracellular vesicles from AML are mainly enriched in stem cell markers and express antioxidant GPX3, with their profiles showing potential prognostic value. Extracellular vesicles enhance mitochondrial functionality and dependence on CD34+ AML cells via the glutathione/GPX4 axis. Notably, extracellular vesicles from adverse-risk patients enhance leukemia cell engraftment in vivo. Here, we show a potential noninvasive approach based on liquid 'cell-extracellular vesicle' biopsy toward a redefined metabolic stratification in AML. The role of metabolism in acute myeloid leukaemia (AML) onset remains to be explored. Here, the authors explore the metabolic landscape of AML cells and the signature of extracellular vesicles (EVs) in peripheral blood and show that circulating EVs regulate leukaemia (stem) cell metabolic reprogramming. [ABSTRACT FROM AUTHOR]

Brain age, a biomarker reflecting brain health relative to chronological age, is increasingly used in neuroimaging to detect early signs of neurodegenerative diseases and support personalized treatment plans. Two primary approaches for brain age prediction have emerged: morphometric feature extraction from MRI scans and deep learning (DL) applied to raw MRI data. However, a systematic comparison of these methods regarding performance, interpretability, and clinical utility has been limited. In this study, we present a comparative evaluation of two pipelines: one using morphometric features from FreeSurfer and the other employing 3D convolutional neural networks (CNNs). Using a multisite neuroimaging dataset, we assessed both model performance and the interpretability of predictions through eXplainable Artificial Intelligence (XAI) methods, applying SHAP to the feature-based pipeline and Grad-CAM and DeepSHAP to the CNN-based pipeline. Our results show comparable performance between the two pipelines in Leave-One-Site-Out (LOSO) validation, achieving state-of-the-art performance on the independent test set ( M A E = 3.21 with DNN and morphometric features and M A E = 3.08 with a DenseNet-121 architecture). SHAP provided the most consistent and interpretable results, while DeepSHAP exhibited greater variability. Further work is needed to assess the clinical utility of Grad-CAM. This study addresses a critical gap by systematically comparing the interpretability of multiple XAI methods across distinct brain age prediction pipelines. Our findings underscore the importance of integrating XAI into clinical practice, offering insights into how XAI outputs vary and their potential utility for clinicians. [ABSTRACT FROM AUTHOR]

Although the electron density can be calculated with the formal resources of quantum mechanics, in physics it does not play the leading role that the quantum state does. In contrast, the concept of electron density is central in quantum chemistry. There is no doubt about how the electron density is computed in terms of the wave function of an atom or molecule. However, when the interpretation of the concept is at stake, there is no general agreement. In this article we will analyze the two main interpretations of the concept of electron density: the Born-style probability density interpretation and the Schrödinger-style charge density interpretation. In particular, we will examine their differences, their relations with quantum mechanics and the consequences that each of them entails from a strictly quantum point of view. [ABSTRACT FROM AUTHOR]

Background: Cardiovascular magnetic resonance (CMR) is the gold-standard to estimate right ventricular (RV) volumes, which are key for clinical management of patients with repaired tetralogy of Fallot (rTOF). Semi-automated threshold-based methods (SAT) have been proposed for CMR post-processing as alternatives to fully manual standard tracing. We investigated the impact of SAT on RV analysis using different thresholds in rTOF patients. Methods: RV volumes and mass were estimated using SAT and standard fully manual tracing methods in rTOF patients. Two threshold levels were set for SAT, i.e., default 50 (SAT-50) and 30(SAT-30). RV stroke volumes (SV) were compared to main pulmonary artery forward flow (MPA-FF). Post-processing time, intra- and interobserver variabilities were compared across methods. Results: Sixty-two CMRs of rTOF patients were analyzed. Compared to the standard fully manual tracing, no significant differences in RV mass, volumes and ejection fraction were observed using SAT-30, whereas SAT-50 significantly underestimated RV end-diastolic-volume index (EDVi) by 10.4% (mean difference of − 11.8 ± 6.2 ml/m2, p 0.03) and overestimated RV mass index by 21.8% (mean difference of 14.2 ± 11.9 g/m2, p 0.002). Compared to MPA-FF, RVSV by standard fully manual method and SAT-30 showed minor biases, respectively, 0.03 ml/m2 and 0.7 ml/m2, while SAT-50 underestimated RVSV by 6.86 ml/m2 (p < 0.001). In six patients, the degree of RV EDVi underestimation by SAT-50 determined a change of category from dilated to non-dilated RV. Intra- and interobserver variabilities were good to excellent for all methods. Post-processing duration was shorter for SAT compared to standard manual segmentation (5.5 ± 1.7 min vs. 19.5 ± 4.4 min, p < 0.001). Conclusion: CMR SAT-30 post-processing is a precise, accurate and time-saving method for biventricular assessment of volumes, ejection fraction and mass in rTOF. [ABSTRACT FROM AUTHOR]

The aim of this study was to estimate the correlations among traits in biomass sorghum, estimate the direct and indirect effects, and check for a cause/effect relationship of the traits on the theoretical calorific value (TCV) through pathway analysis. An additional aim is to provide a complementary technique for analysis of the traits and orientation of breeding programs of biomass sorghum through data mining. A total of 25 hybrids of biomass sorghum were evaluated in a triple square lattice design. The following traits were measured: flowering (FLOW); plant height (PH); fresh biomass yield of the stalk (FBYs), of leaves, and of panicles; dry matter of the stalk and of the leaves (DMl); neutral detergent fiber of the stalk and of the leaves; acid detergent fiber of the stalk and of the leaves; lignin of the stalk and of the leaves; hemicellulose of the stalk and of the leaves; cellulose concentration of the stalk and of the leaves; and the TCV. The data were placed under exploratory analysis, the mixed model approach, pathway analysis based on genotypic correlations, and the regression tree technique. The traits FLOW, PH, FBYs, DMl, and LIG were considered the main determinants of the changes in the TCV and, therefore, with potential for use in indirect selection. The technique of data mining allowed better visualization of the relationships among the traits, assisting in some explanations regarding the effect of the traits on the TCV. [ABSTRACT FROM AUTHOR]

Diastolic vortex ring (VR) plays a key role in the blood-pumping function exerted by the left ventricle (LV), with altered VR structures being associated with LV dysfunction. Herein, we sought to characterize the VR diastolic alterations in ischemic cardiomyopathy (ICM) patients with systo-diastolic LV dysfunction, as compared to healthy controls, in order to provide a more comprehensive understanding of LV diastolic function. 4D Flow MRI data were acquired in ICM patients (n = 15) and healthy controls (n = 15). The λ2 method was used to extract VRs during early and late diastolic filling. Geometrical VR features, e.g., circularity index (CI), orientation (α), and inclination with respect to the LV outflow tract (ß), were extracted. Kinetic energy (KE), rate of viscous energy loss ( EL ˙ ), vorticity (W), and volume (V) were computed for each VR; the ratios with the respective quantities computed for the entire LV were derived. At peak E-wave, the VR was less circular (p = 0.032), formed a smaller α with the LV long-axis (p = 0.003) and a greater ß (p = 0.002) in ICM patients as compared to controls. At peak A-wave, CI was significantly increased (p = 0.034), while α was significantly smaller (p = 0.016) and β was significantly increased (p = 0.036) in ICM as compared to controls. At both peak E-wave and peak A-wave, EL ˙ VR / EL ˙ LV , WVR/WLV, and VVR/VLV significantly decreased in ICM patients vs. healthy controls. KEVR/VVR showed a significant decrease in ICM patients with respect to controls at peak E-wave, while VVR remained comparable between normal and pathologic conditions. In the analyzed ICM patients, the diastolic VRs showed alterations in terms of geometry and energetics. These derangements might be attributed to both structural and functional alterations affecting the infarcted wall region and the remote myocardium. [ABSTRACT FROM AUTHOR]

Aim: Periodic screening for diabetic retinopathy (DR) is effective for preventing blindness. Artificial intelligence (AI) systems could be useful for increasing the screening of DR in diabetic patients. The aim of this study was to compare the performance of the DAIRET system in detecting DR to that of ophthalmologists in a real-world setting. Methods: Fundus photography was performed with a nonmydriatic camera in 958 consecutive patients older than 18 years who were affected by diabetes and who were enrolled in the DR screening in the Diabetes and Endocrinology Unit and in the Eye Unit of ULSS8 Berica (Italy) between June 2022 and June 2023. All retinal images were evaluated by DAIRET, which is a machine learning algorithm based on AI. In addition, all the images obtained were analysed by an ophthalmologist who graded the images. The results obtained by DAIRET were compared with those obtained by the ophthalmologist. Results: We included 958 patients, but only 867 (90.5%) patients had retinal images sufficient for evaluation by a human grader. The sensitivity for detecting cases of moderate DR and above was 1 (100%), and the sensitivity for detecting cases of mild DR was 0.84 ± 0.03. The specificity of detecting the absence of DR was lower (0.59 ± 0.04) because of the high number of false-positives. Conclusion: DAIRET showed an optimal sensitivity in detecting all cases of referable DR (moderate DR or above) compared with that of a human grader. On the other hand, the specificity of DAIRET was low because of the high number of false-positives, which limits its cost-effectiveness. [ABSTRACT FROM AUTHOR]

Purpose: The relationship between autistic traits and eating disturbances has been given considerable attention over the last decades. The rise of a dimensional approach to psychopathology has expanded the way we think about autism, acknowledging that subthreshold autistic manifestations span across the general population and are more pronounced in psychiatric patients. Here we investigated the prevalence of eating disorders and its potential relationship with autistic traits and sensory sensitivity in a group of patients who were referred for the first time to a mental health outpatient clinic, without a formal diagnosis yet. Methods: 259 young adults (between 18 and 24 years old) completed: the Eating Attitude Test (EAT-26), the Swedish Eating Assessment for Autism Spectrum Disorders (SWEAA), the Autism Quotient (AQ), the Ritvo Autism Asperger Diagnostic Scale-Revised (RAADS-R), and the Sensory Perception Quotient—Short Form 35 item (SPQ-SF35). Results: 23.55% of participants scored above the cut-off at the EAT-26, suggesting that they presented a risk for eating disorders and should be assessed by a specialized clinician; associations emerged between hypersensitivity in the touch and vision domain and both the EAT-26 and the SWEAA; the presence of autistic traits was largely associated with eating disturbances. Conclusions: This study underlines the significance of the eating domain as a central psychopathological feature in the distress experienced by young adults with general psychiatric symptoms and psychological suffering; it adds evidence to the association between autistic traits and eating disorders and opens to new research questions about the role of subthreshold autistic traits in general psychopathology. Level of evidence: Level I: Evidence obtained from experimental studies. [ABSTRACT FROM AUTHOR]

The prevalence of cardiovascular events, stroke, and diabetes worldwide underscores the urgent need for effective and minimally invasive treatments. With nearly 20 million annual casualties attributed to cardiovascular diseases and an estimated 463 million people living with diabetes in 2022. Identifying promising therapeutic candidates is paramount. MicroRNAs, short nucleic acids involved in regulating gene expression, emerge as potential game-changers. Among these, microRNA-24 (miR-24), a hypoxia-sensitive player in endothelial vessels, has protective roles against diverse vascular complications. Following heart infarction and stroke, elevating miR-24 expression proves beneficial by mitigating oxidative stress, inflammation, and apoptosis while enhancing cell survival. It reduces cardiac fibrosis in heart disease, regulates aberrant angiogenesis in cerebral hemorrhagic strokes, and enhances the functionality of cardiomyocytes and brain neurons. In diabetic conditions, augmenting miR-24 expression mitigates complications. Further, being miR-24 also expressed by the skeletal muscle (i.e., myo-miR) in response to exercise, this miRNA may participate in the complex molecular network that systemically spreads the beneficial effects of physical exercise. This review provides a comprehensive vision of the molecular mechanisms underpinning the miR-24 protective effects, offering new insights into its therapeutic potential and proposing a novel avenue for medical intervention. Highlights: miR-24 is a promising therapeutic target, sensitive to hypoxia, with diverse protective roles in cardiovascular diseases, stroke, and diabetes. miR-24's protective mechanisms, including anti-apoptotic effects and inflammation modulation, position it as a potential treatment for heart infarction, stroke, and diabetic complications. Reduced miR-24 expression in these conditions suggests its potential as an efficient treatment, pending careful evaluation in (pre)clinical trials. [ABSTRACT FROM AUTHOR]

This study examined the presence of autistic traits in a sample of adult women diagnosed with different Eating Disorders (ED), and explored the concurrent role of autistic traits and sensory sensitivity in influencing both their eating disorder symptomatology and their autism-related eating behaviours. Seventy-five women with different ED (Anorexia Nervosa, Bulimia Nervosa, Binge-Eating Disorder, Other Specified Feeding or Eating Disorder) completed the Eating Attitude Test (EAT-26), the Autism Quotient (AQ), the Ritvo Autism Asperger Diagnostic Scale-Revised (RAADS-R), the Sensory Perception Quotient - Short Form 35 item (SPQ-SF35) and the Swedish Eating Assessment for Autism Spectrum Disorders (SWEAA). Twelve percent of participants scored above the cut-off on both the AQ and the RAADS-R, while 68% scored above the cut-off on the RAADS-R only. A mediation analysis revealed that the association between sensory sensitivity (SPQ-SFR35) and scores on both the EAT-26 and the SWEAA was significantly mediated by the presence of autistic traits (RAADS-R). These findings, first, confirm the presence of autistic traits in individuals with ED; second, they show that a lower sensory threshold (i.e., a higher sensory sensitivity) is associated with a higher presence of autistic traits which were, in turn, positively associated with dysfunctional eating behaviours typical of ED and ASD. This study ultimately highlights the importance of further research on autistic traits across all diagnostic categories of ED. [ABSTRACT FROM AUTHOR]

This study aimed to identify and select superior biomass sorghum genotypes for second-generation ethanol production through multi-environment trials and multiple traits. The efficiency of different selection strategies using the FAI-BLUP index in multi-environment trials (MET) was assessed. Twenty-five biomass sorghum genotypes were evaluated in triple square lattice experiments in three locations in the 2018/2019 agricultural year. Evaluated traits included flowering time (FLOW), plant height (PH), fresh biomass yield (FBY), dry matter content (DM), moisture content (M), dry biomass yield (DBY), as well as the contents of neutral detergent fiber (NDF), acid detergent fiber (ADF), lignin (LIG), hemicellulose (HEM), and cellulose (CC). Each location and MET performed single-trait analyses. Five strategies were performed for selecting superior genotypes using the FAI-BLUP index. Strategy E1 considered BLUPs of genotypes within location, while Strategy E2 used BLUPs of genotype's main effects from MET analyses. Strategy E3 used BLUPs of genotypes within locations (genotype main effects plus genotype by environment interaction—G + GE) from MET analyses. Strategies E4 and E5 used BLUPs from E1 and E3, respectively, assuming traits evaluated at different locations as different traits. Regardless of the strategy, the FAI-BLUP index aimed to enhance the phenotypic expression of FLOW, PH, FBY, DM, DBY, NDF, ADF, HEM, and CC while reducing M and LIG traits to achieve the desired ideotype. Genotypes 4, 13, 17, and 18 exhibited superior performance, predictability, and genotypic adaptability, indicating their potential for second-generation ethanol production. Strategies E2 and E3 emerged as the most effective for selecting superior genotypes using the FAI-BLUP index. [ABSTRACT FROM AUTHOR]

Blood-based biomarkers (BBM) are becoming easily detectable tools to reveal pathological changes in Alzheimer's disease (AD). A comprehensive and up-to-date overview of the association between BBM and brain MRI parameters is not available. This systematic review aimed to summarize the literature on the associations between the main BBM and MRI markers across the clinical AD continuum. A systematic literature search was carried out on PubMed and Web of Science and a total of 33 articles were included. Hippocampal volume was positively correlated with Aβ42 and Aβ42/Aβ40 and negatively with Aβ40 plasma levels. P-tau181 and p-tau217 concentrations were negatively correlated with temporal grey matter volume and cortical thickness. NfL levels were negatively correlated with white matter microstructural integrity, whereas GFAP levels were positively correlated with myo-inositol values in the posterior cingulate cortex/precuneus. These findings highlight consistent associations between various BBM and brain MRI markers even in the pre-clinical and prodromal stages of AD. This suggests a possible advantage in combining multiple AD-related markers to improve accuracy of early diagnosis, prognosis, progression monitoring and treatment response. [ABSTRACT FROM AUTHOR]

Metabolic associated steatotic liver disease (MASLD) is the most common liver condition. It is associated with increased liver-related morbidity and mortality, and also with high risk of cardiovascular events (CVD), representing itself an independent risk factor for it. This makes MASLD a presentation of high interest for internal medicine, also because of its association with metabolic syndrome (MetS). It is crucial to assess its risks in a noninvasive way. With the aim of finding specific risk profiles for CVD development in MASLD by performing a noninvasive assessment of: (1) preclinical signs of endothelial dysfunction (ED); (2) clinical assessment of CVD risk by Framingham Heart Risk Score (FHRs); (3) genomic characterization of MASLD associated polymorphisms; (4) specific untargeted metabolomic profiles, we enrolled 466 MASLD patients non-invasively classified in 4 group of liver fibrosis severity (group-A: low-fibrosis risk, group-B: high-fibrosis risk, group-C: MASLD-cirrhosis, group-D: MASLD-HCC) and 73 healthy controls. FHRs was similar in controls and low-fibrosis group and significantly higher in high-fibrosis patients, cirrhosis, and HCC, increasing among classes. At a multivariable regression, FHRs was associated with liver disease severity and diabetes. 38.2% of patients had altered EndoPAT, resembling ED. Patients with high FHRs (> 40%) and ED had different metabolomics compared to those without ED. Our study reveals that a deep, non-invasive characterization of MASLD patients through precision medicine approaches (untargeted metabolomics, SNPs, ED assessment) was able to show a peculiar pattern in MASLD patients with increased CVD risk, mostly correlated with liver disease severity. [ABSTRACT FROM AUTHOR]

Stuccoes are very delicate decorative elements of Roman age. Very few of them survived almost intact to present days and, for this reason, they are of great interest to restorers and conservators. In this study, we combined metabarcoding and untargeted metabolomics to characterise the taxonomic and metabolic profiles of the microorganisms forming biofilms on the stuccoes located on the ceiling of the laconicum, a small thermal environment in the archaeological park of Baia (southern Italy). We found that some samples were dominated by bacteria while others by eukaryotes. Additionally, we observed high heterogeneity in the type and abundance of bacterial taxa, while the eukaryotic communities, except in one sample (at prevalence of fungi), were dominated by green algae. The metabolic profiles were comparable across samples, with lipids, lipid-like molecules and carbohydrates accounting for roughly the 50% of metabolites. In vitro and in vivo tests to remove biofilms on stuccoes using essential oils blends were successful at a 50% dilution for one hour and half. This integrative study advanced our knowledge on taxonomic and metabolic profiles of biofilms on ancient stuccoes and highlighted the potential impacts of these techniques in the field of cultural heritage conservation. [ABSTRACT FROM AUTHOR]

Lightweighting of electric vehicles is an important consideration to improve range and potentially reduce the vehicle price by downsizing expensive battery and motor components. Aluminum alloys have a combination of light weight, high electrical conductivity and strength that are required in e-motor applications to achieve high power output and efficiency. In this research, Al–Ce based high pressure die casting alloys were investigated in different heat treatment tempers to maximize mechanical properties while maintaining a high electrical conductivity. Testing of tensile properties and electrical conductivity were performed in the as-cast and heat-treated conditions, while microstructural characterization and solidification analysis were performed using scanning electron microscopy and the universal metallurgical simulator and analyzer, respectively. The results suggest that the Al–Ce–Si–Mg alloy had yield strength (YS) exceeding 110 MPa and electrical conductivity of at least 49 pct IACS (28.5 MS/m) in the T5 and T6 conditions, with elevated Fe levels causing a slight reduction in YS and conductivity. This combination of properties makes this alloy a promising alternative to the near pure Al or Cu-based alloys that are currently used in electric induction motors. [ABSTRACT FROM AUTHOR]

Hepatitis E virus (HEV) is primarily transmitted via the fecal–oral route and is considered an anthropozoonosis. Genotypes with zoonotic potential (mainly HEV-3 and HEV-4) can be transmitted through the consumption of raw or undercooked pork, wild boar, deer meat, or processed products. This study aims to explore methodologies for processing meat samples to establish a protocol for HEV detection in meat. The analysis of pre-analytical conditions involved comparing homogenization with PBS versus TRIzol, comparing tissue disruption methods (ultra-turrax versus mortar and pestle), and assessing nucleic acid extraction techniques (spin columns and magnetic beads) across three types of artificially contaminated meat matrices: pork, salmon (fish-meat), and salami. Each test included a process control virus (PP7) and an HEV transcript. Molecular detection was performed via RT-qPCR. Results indicated that TRIzol provided better recovery rates for homogenization, while spin columns were the most effective option for RNA extraction. Both the ultra-turrax homogenizer and the mortar-pestle methods were effective for pork and fish-meat homogenization, while the use of the UT yielded superior results for salami. HEV recovery rates were 36.7%, 26.3%, and 34.1% for salami, salmon, and pork meat, respectively. In conclusion, we reached a simple and reliable protocol for the detection of RNA-HEV from three meat matrices. This method, which includes homogenization with TRIzol, mechanical tissue disruption, and RNA extraction using spin columns followed by real-time PCR, can be applied in future studies to evaluate HEV prevalence in food sources and contribute to the discussion about HEV detection methodologies. [ABSTRACT FROM AUTHOR]

Ti-6Al-4Zr-2Sn-6Mo alloy is one of the most recent titanium alloys processed using powder bed fusion-laser beam (PBF-LB) technology. This alloy has the potential to replace Ti-6Al-4V in automotive and aerospace applications, given its superior mechanical properties, which are approximately 10% higher in terms of ultimate tensile strength (UTS) and yield strength after appropriate heat treatment. In as-built conditions, the alloy is characterized by the presence of soft orthorhombic α″ martensite, necessitating a postprocessing heat treatment to decompose this phase and enhance the mechanical properties of the alloy. Usually, PBFed Ti6246 components undergo an annealing process that transforms the α″ martensite into an α-β lamellar microstructure. The primary objective of this research was to develop a solution treatment and aging (STA) heat treatment tailored to the unique microstructure produced by the additive manufacturing process to achieve an ultrafine bilamellar microstructure reinforced by precipitation hardening. This study investigated the effects of various solution temperatures in the α-β field (ranging from 800 to 875°C), cooling media (air and water), and aging time to determine the optimal heat treatment parameters for achieving the desired bilamellar microstructure. For each heat treatment condition, different α-β microstructures were found, varying in terms of the α/β ratio and the size of the primary α-phase lamellae. Particular attention was given to how these factors were influenced by increases in solution temperature and how microhardness correlated with the percentage of the metastable β phase present after quenching. Tensile tests were performed on samples subjected to the most promising heat treatment parameters. A comparison with literature data revealed that the optimized STA treatment enhanced hardness and UTS by 13% and 23%, respectively, compared with those of the annealed alloy. Fracture surface analyses were conducted to investigate fracture mechanisms. [ABSTRACT FROM AUTHOR]

Candida parapsilosis is an opportunistic fungal pathogen commonly isolated from the environment and associated with nosocomial infection outbreaks worldwide. We describe here the construction of a large collection of gene disruptions, greatly increasing the molecular tools available for probing gene function in C. parapsilosis. We use these to identify transcription factors associated with multiple metabolic pathways, and in particular to dissect the network regulating the assimilation of sulphur. We find that, unlike in other yeasts and filamentous fungi, the transcription factor Met4 is not the main regulator of methionine synthesis. In C. parapsilosis, assimilation of inorganic sulphur (sulphate) and synthesis of cysteine and methionine is regulated by Met28, a paralog of Met4, whereas Met4 regulates expression of a wide array of transporters and enzymes involved in the assimilation of organosulfur compounds. Analysis of transcription factor binding sites suggests that Met4 is recruited by the DNA-binding protein Met32, and Met28 is recruited by Cbf1. Despite having different target genes, Met4 and Met28 have partial functional overlap, possibly because Met4 can contribute to assimilation of inorganic sulphur in the absence of Met28. The fungus Candida parapsilosis is found in the environment and associated with nosocomial infection outbreaks. Here, Lombardi et al. generate a large collection of gene disruptions in this opportunistic pathogen and identify transcription factors associated with multiple metabolic pathways, revealing unique features in the regulation of sulphur assimilation. [ABSTRACT FROM AUTHOR]

Background: Complexity in landscape structure is often assessed using individual metrics related to ecological processes. However, this rarely incorporates important relationships among metrics and may miss landscape structure effects. Multivariate statistics provide techniques for assessing overall landscape structure effects. We assessed how multivariate statistics could be used to connect landscape structure with an ecological process [bobcat (Lynx rufus) wildlife crossing structure (WCS) use]. We tested how landscape structure at WCS sites compared to the surrounding landscape and how structure affected detections at WCS sites. Our study was conducted in Cameron County, Texas, USA where WCSs are in various stages of construction and monitoring. We used a classified land use/land cover map and aerial LiDAR to calculate configuration and density metrics at WCS and random sites. We created indices for configuration and density using principal components analysis to assess landscape structure effects on camera trap detections at WCSs. Results: Landscape structure at WCSs did not differ from random locations. Wildlife crossing structure use increased with greater woody cover and decreased with increasing vegetation density. Our indices allowed identification of differences in how configuration and density impacted WCS use. Ordination methods helped identify individual contributions of landscape metrics to the overall landscape structure effect. Conclusions: Wildlife crossing structures are permanent fixtures on landscapes, so selecting appropriate locations using broad-scale landscape structure likely increases target species use. Using indices of landscape structure provides planners with a more holistic approach to WCS placement and provides a more comprehensive picture of landscape pattern and process relationships. [ABSTRACT FROM AUTHOR]

Industrialized environments, despite benefits such as higher levels of formal education and lower rates of infections, can also have pernicious impacts upon brain atrophy. Partly for this reason, comparing age-related brain volume trajectories between industrialized and non-industrialized populations can help to suggest lifestyle correlates of brain health. The Tsimane, indigenous to the Bolivian Amazon, derive their subsistence from foraging and horticulture and are physically active. The Moseten, a mixed-ethnicity farming population, are physically active but less than the Tsimane. Within both populations (N = 1024; age range = 46–83), we calculated regional brain volumes from computed tomography and compared their cross-sectional trends with age to those of UK Biobank (UKBB) participants (N = 19,973; same age range). Surprisingly among Tsimane and Moseten (T/M) males, some parietal and occipital structures mediating visuospatial abilities exhibit small but significant increases in regional volume with age. UKBB males exhibit a steeper negative trend of regional volume with age in frontal and temporal structures compared to T/M males. However, T/M females exhibit significantly steeper rates of brain volume decrease with age compared to UKBB females, particularly for some cerebro-cortical structures (e.g., left subparietal cortex). Across the three populations, observed trends exhibit no interhemispheric asymmetry. In conclusion, the age-related rate of regional brain volume change may differ by lifestyle and sex. The lack of brain volume reduction with age is not known to exist in other human population, highlighting the putative role of lifestyle in constraining regional brain atrophy and promoting elements of non-industrialized lifestyle like higher physical activity. [ABSTRACT FROM AUTHOR]

Purpose of the review: Although calcium pyrophosphate deposition (CPPD) has been known since the 1960s, our understanding of its pathogenesis remains rudimentary. This review aims to illustrate the known mechanisms underlying calcium pyrophosphate (CPP) crystal formation and deposition and explore future directions in research. By examining various perspectives, from basic research to clinical and imaging assessments, as well as new emerging methodologies, we can establish a starting point for a deeper understanding of CPPD pathogenesis. Recent Findings: Recent years have seen significant advances in CPPD research, particularly in the clinical field with the development of the 2023 ACR/EULAR classification criteria for CPPD disease, and in imaging with the introduction of the OMERACT ultrasonographic definitions and scoring system. However, progress in basic research has been slower. New laboratory approaches, such as Raman spectroscopy and omics sciences, offer promising insights that may help piece together the puzzle of CPPD. Summary: CPPD is a common yet understudied condition. As the population ages and CPPD becomes more prevalent, there is an urgent need to better understand the disease and the mechanisms involved in crystal formation and deposition, in order to improve diagnosis and therapeutic approaches. [ABSTRACT FROM AUTHOR]

Background: Colistin, administered as intravenous colistimethate (CMS), is still used in the critical care setting and current guidelines recommend high dosage CMS in patients undergoing continuous renal replacement therapy (CRRT). Due to the paucity of real-life data, we aimed to describe colistin pharmacokinetic/pharmacodynamic (PK/PD) profile in a cohort of critically ill patients with infections due to carbapenem-resistant (CR) bacteria undergoing CRRT. Results: All consecutive patients admitted to three Intensive Care Units (ICUs) of a large metropolitan University Hospital, treated with colistin for at least 48 h at the dosage of 6.75 MUI q12, after 9 MIU loading dose, and undergoing CRRT were included. After the seventh dose, patients underwent blood serial sampling during a time frame of 24 h. We included 20 patients, who had CR-Acinetobacter baumannii ventilator-associated pneumonia and were characterized by a median SAPS II and SOFA score of 41 [34.5–59.3] and 9 [6.7–11], respectively. Fifteen patients died during ICU stay and six recovered renal function. Median peak and trough colistin concentrations were 16.6 mcg/mL [14.8–20.6] and 3.9 mcg/mL [3.3–4.4], respectively. Median area under the time–concentration curve (AUC0 − 24) and average steady-state concentration (Css, avg) were 193.9 mcg h/mL [170.6–208.6] and 8.07 mcg/mL [7.1–8.7]. Probability of target attainment of colistin pharmacodynamics according to the fAUC0 − 24/MIC target ≥ 12 was 100% for MIC ≤ 2 mcg/mL and 85% for MIC = 4 mcg/ML, although exceeding the toxicity limit of Css, avg 3–4 mcg/mL. Conclusions: In critically ill patients with CR infections undergoing CRRT, recommended CMS dosage resulted in colistin plasmatic levels above bacterial MIC90, but exceeding the safety Css, avg. limit. Trial registration: This trial was registered in ClinicalTrials.gov on 23/07/2021 with the ID NCT04995133 (https//clinicaltrials.gov/study/NCT04995133). [ABSTRACT FROM AUTHOR]

We reconcile two significant lines of Cognitive Neuroscience research: the relationship between the structural and functional architecture of the brain and behaviour on the one hand and the functional significance of oscillatory brain processes to behavioural performance on the other. Network neuroscience proposes that the three elements, behavioural performance, EEG oscillation frequency, and network connectivity should be tightly connected at the individual level. Young and old healthy adults were recruited as a proxy for performance variation. An auditory inhibitory control task was used to demonstrate that task performance correlates with the individual EEG frontal theta frequency. Older adults had a significantly slower theta frequency, and both theta frequency and task performance correlated with the strengths of two network connections that involve the main areas of inhibitory control and speech processing. The results suggest that both the recruited functional network and the oscillation frequency induced by the task are specific to the task, are inseparable, and mark individual differences that directly link structure and function to behaviour in health and disease. [ABSTRACT FROM AUTHOR]

The development of high-strength advanced additively manufactured (AM) aluminum alloys is driven by the need for weight reduction in complex-shaped structural applications. In this context, heat-treatable aluminum-scandium alloy, known commercially as Scalmalloy®, offers high strength and lightness, also at high temperatures, due to solution strengthening Al3(Sc, Zr) particles. A widespread diffusion of such AM alloy is also related to welding technologies that could preserve its engineered microstructure. This study investigates the microstructural and mechanical properties of butt friction stir welding (FSW) joints of LPBF Scalmalloy® plates under different welding settings. Joint performance was evaluated under quasi-static and cyclic loading conditions. Porosity in Scalmalloy® and welds was assessed using 3D X-ray computed tomography. An aging heat treatment assessed the extent of precipitation hardening in the FSW joints. Results show that metal stirring during FSW notably reduced the intrinsic porosity of Scalmalloy®, decreasing the equivalent pore diameter from about 200 μm to 60 μm in the welded joints. Under quasi-static loading, welded specimens failed at the interface between the thermo-mechanically affected and the stir zones on the advancing side. The aging heat treatment improved the mechanical strength of Scalmalloy® from approximately 400 to 480 MPa, albeit at the expense of ductility (elongation at fracture decreased from 16 to 4%). The higher heat input and stirring developed at a low welding speed reduced lazy S defects but limited the effectiveness of subsequent aging. In fatigue testing, welded joints consistently failed within the aged base material due to the intrinsic porosity of Scalmalloy®. [ABSTRACT FROM AUTHOR]

Tri-boson production together with vector-boson scattering is a privileged channel to study the electroweak structure of the Standard Model. Upcoming LHC running stages will allow to measure these processes at unprecedented accuracy and for all possible final states, which requires to push theory predictions to still unexplored frontiers. In this work we present the first calculation for the process pp → μ+μ−e+νejj at the LHC in a tri-boson phase space. We evaluate the three LO contributions, namely the O (α6), which contains the genuine tri-boson signature, along with the O (αsα5) and O ( α s 2 α4), and the two O (α7) and O (αsα6) NLO corrections. The calculation is based on full Standard-Model matrix elements, including all resonant and non-resonant terms, complete spin correlations and interference effects. Integrated and differential cross sections are presented for a fiducial region inspired by High Luminosity LHC prospect studies. We find electroweak corrections of −14% for the fiducial cross section, almost twice as large as for other tri-boson processes. [ABSTRACT FROM AUTHOR]

Background: Sarcopenia, defined as the loss of skeletal muscle mass, has been associated with a worse functional outcome after stroke. Measurement of temporal muscle thickness (TMT) has been introduced as an easily obtainable surrogate marker to identify patients with sarcopenia. Our study aims to investigate the correlation between pre-stroke sarcopenia, measured by TMT assessment, and functional outcome in patients treated with revascularization procedures for acute ischemic stroke. Methods: We included consecutive adult patients who underwent thrombolysis, endovascular thrombectomy or both for acute ischemic stroke at our Centre from January 2020 to June 2022. Besides collecting baseline clinical and neuroradiological features, TMT was measured on brain computed tomography scans according to a standardized protocol. Modified Rankin Scale (mRS) scores at 3 months represented the main endpoint of functional outcome. Results: A total of 261 patients were available for the analysis. In univariate models, patients with excellent outcomes (mRS = 0–1) were younger, had higher TMT values and lower pre-event disability and stroke severity. In multivariate models higher TMT values resulted independently associated with reduced mortality (Odds Ratio 0.708, 95% Confidence Interval 0.538–0.930, p = 0.013). Age, diabetes, brain bleeding events and stroke severity were found to be predictors of mortality, too. Conclusions: Our retrospective analysis shows that in patients who underwent revascularization treatments for ischemic stroke TMT is as an independent predictor of survival easily obtainable from the baseline CT scan. Further investigation is required to confirm the role of sarcopenia assessment and TMT measurement in the prognostication toolkit of this disease. [ABSTRACT FROM AUTHOR]

Our technological, information-rich society thrives because of scientific thinking. However, a comprehensive theory of the development of scientific thinking remains elusive. Building on previous theoretical and empirical work in conceptual change, the role of credibility and plausibility in evaluating scientific evidence and claims, science engagement, active learning in STEM education, and the development of empirical thinking, we chart a pathway toward a comprehensive theory of the development of scientific thinking as an example of theory building in action. We detail the structural similarity and progressive transformation of our models and perspectives, highlighting factors for incorporation into a novel theory. This theory will focus on beneficial outcomes of a more collaborative scientific community and increasing scientific literacy through deeper science understanding for all people. [ABSTRACT FROM AUTHOR]

Introduction: Epistaxis is the most common otorhinolaryngological emergency and historically there have been an important debate whether there is a cause-effect relationship with high blood pressure. Aim: This retrospective study explored whether hypertension is a significant risk factor for epistaxis in Emergency Department (ED) patients and examined associations between blood pressure levels and epistaxis episodes. Materials and Methods: Two groups were studied: Group A (patients with epistaxis) and Group B (control). Patient characteristics, comorbidities, and medication use were recorded. Blood pressure measurements were taken upon ED arrival and after specialist evaluation. Statistical analyses included descriptive statistics, T-test, χ2 test, and logistic regression. Results: Group A, enrolled from April 2014 to February 2015, included 102 patients, mean age 67, male-female ratio 2:1. Blood pressure on arrival was over 140/90 mmHg in 73%, decreasing to 26% after 30 minutes. Group B, enrolled from May 2023 to August 2023, included 126 patients, mean age 59, male-female ratio 2:1. Blood pressure on arrival was over 140/90 mmHg in 60%, decreasing to 23% after 30 minutes. Both groups showed reduced blood pressure post-evaluation. Logistic regression identified anticoagulant and/or antiplatelet therapy as the main independent risk factor for epistaxis. Age, sex, blood pressure levels, and hypertension did not significantly influence epistaxis occurrence. Conclusion: No significant correlation between hypertension and epistaxis was found. Anticoagulant and/or antiplatelet therapy was the primary independent risk factor, highlighting the importance of considering medication history in evaluating epistaxis. [ABSTRACT FROM AUTHOR]

Purpose: No standard treatment has yet been established for recurrent glioblastoma (GBM). In this context, the aim of the current study was to evaluate safety and efficacy of reirradiation (re-RT) by radiosurgery or fractionated stereotactic radiotherapy (SRS/FSRT) in association with regorafenib. Methods: Patients with a histological or radiological diagnosis of recurrent GBM who received re-RT by SRS/FSRT and regorafenib as second-line systemic therapy were included in the analysis. Results: From January 2020 to December 2022, 21 patients were evaluated. The median time between primary/adjuvant RT and disease recurrence was 8 months (range 5–20). Median re-RT dose was 24 Gy (range 18–36 Gy) for a median number of 5 fractions (range 1–6). Median regorafenib treatment duration was 12 weeks (range 3–26). Re-RT was administered before starting regorafenib or in the week off regorafenib during the course of chemotherapy. The median and the 6‑month overall survival (OS) from recurrence were 8.4 months (95% confidence interval [CI] 6.9–12.7 months) and 75% (95% CI 50.9–89.1%), respectively. The median progression-free survival (PFS) from recurrence was 6 months (95% CI 3.7–8.5 months). The most frequent side effects were asthenia that occurred in 10 patients (8 cases of grade 2 and 2 cases of grade 3), and hand–foot skin reaction (2 patients grade 3, 3 patients grade 2). Adverse events led to permanent regorafenib discontinuation in 2 cases, while in 5/21 cases (23.8%), a dose reduction was administered. One patient experienced dehiscence of the surgical wound after reintervention and during regorafenib treatment, while another patient reported intestinal perforation that required hospitalization. Conclusion: For recurrent GBM, re-RT with SRT/FSRT plus regorafenib is a safe treatment. Prospective trials are necessary. [ABSTRACT FROM AUTHOR]

Novel chimeric antigen receptor (CAR) T-cell approaches are needed to improve therapeutic efficacy in solid tumors. High-risk neuroblastoma is an aggressive pediatric solid tumor that expresses cell-surface GPC2 and GD2 with a tumor microenvironment infiltrated by CD16a-expressing innate immune cells. Here we engineer T-cells to express a GPC2-directed CAR and simultaneously secrete a bispecific innate immune cell engager (BiCE) targeting both GD2 and CD16a. In vitro, GPC2.CAR-GD2.BiCE T-cells induce GPC2-dependent cytotoxicity and secrete GD2.BiCE that promotes GD2-dependent activation of antitumor innate immunity. In vivo, GPC2.CAR-GD2.BiCE T-cells locally deliver GD2.BiCE and increase intratumor retention of NK-cells. In mice bearing neuroblastoma patient-derived xenografts and reconstituted with human CD16a-expressing immune cells, GD2.BiCEs enhance GPC2.CAR antitumor efficacy. A CAR.BiCE strategy should be considered for tumor histologies where antigen escape limits CAR efficacy, especially for solid tumors like neuroblastoma that are infiltrated by innate immune cells. GPC2 and GD2 have been described as immunotherapeutic targets in neuroblastoma. Here the authors engineer T cells to simultaneously express a GPC2-directed CAR and a bispecific innate immune cell engager targeting GD2 and CD16a, showing antitumor activity in neuroblastoma preclinical models. [ABSTRACT FROM AUTHOR]

Background: Administrative healthcare databases, such as Medicare, are increasingly used to identify groups at risk of a crash. However, they only contain information on crash-related injuries, not all crashes. If the driver characteristics associated with crash and crash-related injury differ, conflating the two may result in ineffective or imprecise policy interventions. Methods: We linked 10 years (2008–2017) of Medicare claims to New Jersey police crash reports to compare the demographics, clinical diagnoses, and prescription drug dispensings for crash-involved drivers ≥ 68 years with a police-reported crash to those with a claim for a crash-related injury. We calculated standardized mean differences to compare characteristics between groups. Results: Crash-involved drivers with a Medicare claim for an injury were more likely than those with a police-reported crash to be female (62.4% vs. 51.8%, standardized mean difference [SMD] = 0.30), had more clinical diagnoses including Alzheimer's disease and related dementias (13.0% vs. 9.2%, SMD = 0.20) and rheumatoid arthritis/osteoarthritis (69.5% vs 61.4%, SMD = 0.20), and a higher rate of dispensing for opioids (33.8% vs 27.6%, SMD = 0.18) and antiepileptics (12.9% vs 9.6%, SMD = 0.14) prior to the crash. Despite documented inconsistencies in coding practices, findings were robust when restricted to claims indicating the injured party was the driver or was left unspecified. Conclusions: To identify effective mechanisms for reducing morbidity and mortality from crashes, researchers should consider augmenting administrative datasets with information from police crash reports, and vice versa. When those data are not available, we caution researchers and policymakers against the tendency to conflate crash and crash-related injury when interpreting their findings. [ABSTRACT FROM AUTHOR]

Measuring vector-boson scattering beyond the fully-leptonic final state is becoming possible at the LHC, which demands to have a solid control on the theory predictions for all final states of this class of processes. In this work we present a full off-shell leading-order calculation for the process pp → ℓ+νℓ + 4j in two fiducial regions which are particularly relevant for its experimental measurement. In addition to the fully electroweak order, i.e. O α 6 , we complement our results with O α s α 5 and O α s 2 α 4 for inclusive predictions. At O α 6 we present for the first time a systematic treatment of the process in double-pole approximation and we perform a detailed study of its range of validity by considering inclusive and differential predictions compared to the full off-shell calculation. [ABSTRACT FROM AUTHOR]

Sustainable Development Goals (SDGs) show the breadth of the concept of sustainability and indicate the changes that are needed to provide a future for next generations. A quantitative approach allows the performance of several countries to be framed to assess the state of progress. This work is based on multicriteria decision analysis (MCDA) in which 58 indicators referring to the period 2018–2020 are considered and the performance of 27 European countries is compared. The MCDA makes it possible to calculate a SDG Index that rewards Sweden with positive results also for the Netherlands, Denmark, and Finland. The overall value is broken down by the three dimensions of sustainability (economic, environmental and social) in which again Sweden excels and has also a leadership position in two macro-goals such as security and energy. In contrast, Denmark prevails in innovative future and Netherlands in waste circularity. The main implications of this work confirm that Europe is proceeding to the SDGs goals in an uneven manner, and therefore, there is a need to identify a program that will see greater cooperation among several countries. In fact, Europe will be united when it pursues together a pragmatic vision of sustainability that goes beyond ideology in order to identify solutions that will benefit more stakeholders. [ABSTRACT FROM AUTHOR]

Background: Lung ultrasonography (LUS) is a non-invasive imaging method used to diagnose and monitor conditions such as pulmonary edema, pneumonia, and pneumothorax. It is precious where other imaging techniques like CT scan or chest X-rays are of limited access, especially in low- and middle-income countries with reduced resources. Furthermore, LUS reduces radiation exposure and its related blood cancer adverse events, which is particularly relevant in children and young subjects. The score obtained with LUS allows semi-quantification of regional loss of aeration, and it can provide a valuable and reliable assessment of the severity of most respiratory diseases. However, inter-observer reliability of the score has never been systematically assessed. This study aims to assess experienced LUS operators' agreement on a sample of video clips showing predefined findings. Methods: Twenty-five anonymized video clips comprehensively depicting the different values of LUS score were shown to renowned LUS experts blinded to patients' clinical data and the study's aims using an online form. Clips were acquired from five different ultrasound machines. Fleiss-Cohen weighted kappa was used to evaluate experts' agreement. Results: Over a period of 3 months, 20 experienced operators completed the assessment. Most worked in the ICU (10), ED (6), HDU (2), cardiology ward (1), or obstetric/gynecology department (1). The proportional LUS score mean was 15.3 (SD 1.6). Inter-rater agreement varied: 6 clips had full agreement, 3 had 19 out of 20 raters agreeing, and 3 had 18 agreeing, while the remaining 13 had 17 or fewer people agreeing on the assigned score. Scores 0 and score 3 were more reproducible than scores 1 and 2. Fleiss' Kappa for overall answers was 0.87 (95% CI 0.815–0.931, p < 0.001). Conclusions: The inter-rater agreement between experienced LUS operators is very high, although not perfect. The strong agreement and the small variance enable us to say that a 20% tolerance around a measured value of a LUS score is a reliable estimate of the patient's true LUS score, resulting in reduced variability in score interpretation and greater confidence in its clinical use. [ABSTRACT FROM AUTHOR]

Background: CFTR-related disorder (CFTR-RD) is a clinical entity associated to complex diagnostic paths and newly upgraded standard of care. In CFTR-RD, CFTR genotyping represents a diagnostic surrogate marker. In case of novel haplotype, the diagnosis could represents an area of concern. We described the molecular evaluation of the rare CFTR variant E583G identified in trans with the F508del in a novel haplotype. Methods and results: An adult woman was referred to our pulmonary unit for persistent respiratory symptoms. CFTR Next Generation Sequencing was performed to evaluate full-gene mutational status. The variant identified was evaluated for its pathogenicity integrating clinical evidences with dedicated bioinformatics analyses. Clinical evaluation of patient matched with a mono-organ CFTR-RD diagnosis. Genotyping revealed the novel CFTR haplotype F508del/E583G. Multiple evidences of a deleterious effect of the CFTR E583G rare variant emerged from the bioinformatics analyses performed. Conclusions: Guidelines for CFTR-RD are available with the purpose of harmonizing clinical and molecular investigations. In such context, the identification of novel CFTR haplotype need to a deeper evaluation with a combination of skills. The novel E583G variant could be considered of clinical interest and overall a CFTR-RD Variants of Varying Clinical Consequences. [ABSTRACT FROM AUTHOR]

Neuronal responses during behavior are diverse, ranging from highly reliable 'classical' responses to irregular 'non-classically responsive' firing. While a continuum of response properties is observed across neural systems, little is known about the synaptic origins and contributions of diverse responses to network function, perception, and behavior. To capture the heterogeneous responses measured from auditory cortex of rodents performing a frequency recognition task, we use a novel task-performing spiking recurrent neural network incorporating spike-timing-dependent plasticity. Reliable and irregular units contribute differentially to task performance via output and recurrent connections, respectively. Excitatory plasticity shifts the response distribution while inhibition constrains its diversity. Together both improve task performance with full network engagement. The same local patterns of synaptic inputs predict spiking response properties of network units and auditory cortical neurons from in vivo whole-cell recordings during behavior. Thus, diverse neural responses contribute to network function and emerge from synaptic plasticity rules. How synaptic plasticity rules lead to diverse neural responses in a spiking neural network model remains poorly understood. Here, the authors show how a diversity of response types contributes to network function and task performance. [ABSTRACT FROM AUTHOR]

Research on exploring the relationship between computational thinking and domain specific knowledge gains (i.e. biological evolution) are becoming more common in science education research. The mechanisms behind these relationships are not well understood, particularly between computational practices and biological evolution content knowledge. Increased computational complexity (i.e. simple to complex) may support a greater comprehension of scales or levels of biological organization (i.e. micro to macro) within the context of biological evolution learning. We made use of quantitative methods from qualitative work in the form of coding and relational analysis to identify which biological levels of organization students addressed, how students made connections between these levels and the level of computational complexity displayed during evolution learning with the use of two computational interventions. The aim of this study was not only exploring the biological levels and biological level connections made during the computational thinking interventions, but also analysis of the differences between these two interventions. The results illuminated that use of specific biological levels, biological level connections and differences in computational complexity were distinguishable and there were significant differences between the interventions. These factors may contribute to better understanding of biological evolution knowledge gains. [ABSTRACT FROM AUTHOR]

Monoclonal antibodies targeting interleukin (IL)-5 pathways have revolutionized the treatment expectations for eosinophilic-associated conditions, particularly in patients with respiratory involvement. Mepolizumab (IL-5 antagonist monoclonal antibody), benralizumab (IL-5 receptor blocker monoclonal antibody), and reslizumab (IL-5 antagonist monoclonal antibody) have collectively contributed to the overall improvement of the disease burden in various conditions. Eosinophilic asthma currently boasts the most robust evidence across all age groups: all three biologics are approved for adults (aged ≥18 years); mepolizumab is approved by the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) also in children (aged ≥ 6 years), while bernalizumab was recently approved by the FDA for patients aged ≥6 years in the USA. In chronic rhinosinusitis with nasal polyps, subcutaneous mepolizumab is the only anti-IL-5 therapy approved so far and can be used in adult patients (aged ≥18 years). For eosinophilic esophagitis, conflicting evidence surrounds both mepolizumab, reslizumab, and benralizumab, leading to non-approval of these agents by the FDA/EMA. Recently, mepolizumab was approved for eosinophilic granulomatosis with polyangiitis patients aged ≥6 years or older and for hypereosinophilic syndrome adult patients. A phase III trial proving noninferiority of benralizumab versus mepolizumab in eosinophilic granulomatosis with polyangiitis has been recently published, while evidence on reslizumab is scant. Overall, current evidence on anti-IL-5 biologics for eosinophilic-associated disorders is mostly focused on adults, whereas data for individuals aged under 18 years and over 65 years are scarce, resulting in a lack of evidence, particularly regarding efficacy, for the use of anti-IL-5 agents in these specific patient populations. This review addresses high-quality evidence from randomized controlled trials and real-world post-marketing studies regarding the use of anti-IL-5 therapies for eosinophilic-associated disorders across all age groups, spanning childhood, adulthood, and older age. [ABSTRACT FROM AUTHOR]