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Abstract Background Hereditary transthyretin (ATTRv) amyloidosis is rare, autosomal dominant disease with a fatal outcome if left untreated. Early stages detection is crucial for intervention. We aimed identifying early indexes of cardiac involvement and their eventual correlation with neurological indexes, in pre-symptomatic subjects with TTR gene mutation. Methods Sixteen TTR-mutation carriers (mean age 51 ± 9 years, 6 males, 7 with Val30Met and 9 with Phe64Leu mutation) without left ventricular hypertrophy were studied. Predicted Age of Disease Onset (PADO) and time to PADO (Time-to PADO = PADO-age at evaluation) were computed. Subjects underwent: cardiological and echocardiographic assessment including global longitudinal strain (GLS); tactile and thermal quantitative sensory testing (QST); Perugini score by bone scintigraphy. Results Time to PADO was 30 ± 15 years. Nine subjects showed abnormal GLS (> −20%), unrelated to age, LVMi, MWT, E/e’, NT-proBNP or Time-to PADO. QST findings were abnormal in most subjects. At a worse cold pain threshold corresponded a worse GLS (r = 0.786, p

Hemp (Cannabis sativa L.) is an annual plant belonging to the family of Cannabaceae with several varieties characterized by different fatty acid profile, content in flavonoids, polyphenols, and cannabinoid compounds. Hemp is mostly used in livestock nutrition as oil or as protein cake, but not as inflorescences. The aim of this study was to evaluate the effect of dietary hemp inflorescences on milk yield and composition in grazing dairy goats. Twenty Camosciata delle Alpi goats at their 3rd parity and with a mean body weight of 45.2 ± 2.0 kg, immediately after kidding, were equally allocated into two groups (G: Grazing and GH: grazing and hemp). For three months, all goats were fed on a permanent pasture and received 700/head/day of concentrate; diet of group GH was supplemented with 20 g/head/day of hemp inflorescences. Goats’ body weight did not change during the trial. Individual milk yield was daily recorded and samples collected every 20 days for chemical composition and fatty acid profile analysis. No significant differences were found for milk yield and chemical composition. Caproic (C6:0) (1.80 vs. 1.74%; p

Abstract Background Despite advancements in therapeutic approaches, including taxane-based chemotherapy and androgen receptor-targeting agents, metastatic castration-resistant prostate cancer (mCRPC) remains an incurable tumor, highlighting the need for novel strategies that can target the complexities of this disease and bypass the development of drug resistance mechanisms. We previously demonstrated the synergistic antitumor interaction of valproic acid (VPA), an antiepileptic agent with histone deacetylase inhibitory activity, with the lipid-lowering drug simvastatin (SIM). This combination sensitizes mCRPC cells to docetaxel treatment both in vitro and in vivo by targeting the cancer stem cell compartment via mevalonate pathway/YAP axis modulation. Methods Here, using a combined proteomic and metabolomic/lipidomic approach, we characterized tumor samples derived from 22Rv1 mCRPC cell-xenografted mice treated with or without VPA/SIM and performed an in-depth bioinformatics analysis. Results We confirmed the specific impact of VPA/SIM on the Hippo–YAP signaling pathway, which is functionally related to the modulation of cancer-related extracellular matrix biology and metabolic reprogramming, providing further insights into the molecular mechanism of the antitumor effects of VPA/SIM. Conclusions In this study, we present an in-depth exploration of the potential to repurpose two generic, safe drugs for mCRPC treatment, valproic acid (VPA) and simvastatin (SIM), which already show antitumor efficacy in combination, primarily affecting the cancer stem cell compartment via MVP/YAP axis modulation. Bioinformatics analysis of the LC‒MS/MS and 1H‒NMR metabolomics/lipidomics results confirmed the specific impact of VPA/SIM on Hippo–YAP.

Abstract 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 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.

Sarcomas present challenges in management due to their aggressive nature. Interventional radiology, utilizing ablation and embolization, offer promising alternatives for recurrent cases. In recent years, combined techniques (ablation + embolization) and the use of balloon-microcatheter have been introduced to enhance the necrotic effect in HCC treatment. This paper presents the case of a 47-year-old female with recurrent abdominal sarcoma treated with balloon-occluded microwave ablation (b-MWA) and balloon-occluded transarterial embolization (b-TAE). Post-treatment imaging revealed a significant reduction in lesion size and absence of pathological contrast enhancement. This study highlights the potential of balloon-catheter-assisted combined therapies (b-MWA + b-TAE) in managing sarcomas, expanding the applicability of interventional radiology for inoperable cases that are too large for ablative therapy alone or requiring multiple antennas. Further research is warranted to refine protocols and enhance patient outcomes in sarcoma management.

Abstract MicroRNAs are involved in breast cancer development and progression, holding potential as biomarkers and therapeutic targets or tools. The roles of miR-20a-5p, a member of the oncogenic miR-17-92 cluster, remain poorly understood in the context of breast cancer. In this study, we elucidate the role of miR-20a-5p in breast cancer by examining its associations with breast cancer risk factors and clinicopathological features, and its functional roles in vitro. Tissue microarrays from 313 CAMO cohort breast cancer surgical specimens were constructed, in situ hybridization was performed and miR-20a-5p expression was semiquantitatively scored in tumor stromal fibroblasts, and in the cytoplasm and nuclei of cancer cells. In vitro analysis of the effect of miR-20a-5p transfection on proliferation, migration and invasion was performed in three breast cancer cell lines. High stromal miR-20a-5p was associated with higher Ki67 expression, and higher odds of relapse, compared to low expression. Compared to postmenopausal women, women who were premenopausal at diagnosis had higher odds of high stromal and cytoplasmic miR-20a-5p expression. Cytoplasmic miR-20a-5p was significantly associated with tumor grade. In tumors with high cytoplasmic miR-20a-5p expression compared to low expression, there was a tendency towards having a basal-like subtype and high Ki67. In contrast, high nuclear miR-20a-5p in cancer cells was associated with smaller tumor size and lower odds of lymph node metastasis, compared to low nuclear expression. Transfection with miR-20a-5p in breast cancer cell lines led to increased migration and invasion in vitro. While the majority of our results point towards an oncogenic role, some of our findings indicate that the associations of miR-20a-5p with breast cancer related risk factors and outcomes may vary based on tissue- and subcellular location. Larger studies are needed to validate our findings and further investigate the clinical utility of miR-20a-5p.

Abstract 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.

Abstract Background Understanding the level of exposure to Lassa virus (LASV) in at-risk communities allows for the administration of effective preventive interventions to mitigate epidemics of Lassa fever. We assessed the seroprevalence of LASV antibodies in rural and semiurban communities of two cosmopolitan cities in Nigeria with poorly understood Lassa epidemiology. Methods A cross-sectional study was conducted in ten communities located in the Abuja Municipal Area Council (AMAC), Abuja, and Ikorodu Local Government Area (LGA), Lagos, from February 2nd to July 5th, 2022. Serum samples collected from participants were analyzed for IgG and IgM antibodies using a ReLASV® Pan-Lassa NP IgG/IgM enzyme-linked immunosorbent assay (ELISA) kit. A questionnaire administered to participants collected self-reported sociodemographic and LASV exposure information. Seroprevalence of LASV IgG/IgM was estimated overall, and by study site. Univariate and multivariate log-binomial models estimated unadjusted and adjusted prevalence ratios (aPRs) and 95% confidence intervals (CI) for site-specific risk factors for LASV seropositivity. Grouped Least Absolute Shrinkage and Selection Operator (LASSO) was used for variable selection for multivariate analysis. Results A total of 628 participants with serum samples were included in the study. Most participants were female (434, 69%), married (459, 73%), and had a median age of 38 years (interquartile range 28–50). The overall seroprevalence was 27% (171/628), with a prevalence of 33% (126/376) in Abuja and 18% (45/252) in Lagos. Based on site-specific grouped LASSO selection, enrollment in the dry season (vs. wet; aPR, 95% CI: 1.73, 1.33–2.24), reported inconsistent washing of fruits and vegetables (aPR, 95% CI: 1.45, 1.10–1.92), and a positive malaria rapid test (aPR, 95% CI: 1.48, 1.09-2.00) were independently associated with LASV seropositivity in Abuja, whereas, only a self-reported history of rhinorrhea (PR, 95% CI: 2.21, 1.31–3.72) was independently associated with Lassa seropositivity in Lagos. Conclusions The LASV seroprevalence was comparable to that in other areas in Nigeria. Our findings corroborate those from other studies on the importance of limiting human exposure to rodents and focusing on behavioral factors such as poor hygiene practices to reduce exposure to LASV.

Abstract 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 Aims The use of loop diuretics in pulmonary arterial hypertension (PAH) is less frequent compared with heart failure. The clinical and prognostic characteristics of PAH patients according to loop diuretic use remain unexplored. In this study, we retrospectively analysed the characteristics and survival of PAH patients requiring different doses of loop diuretics. Methods and results Patients diagnosed with PAH between 2001 and 2022 at seven European centres for the management of PAH. According to the median equivalent dose of furosemide in the overall cohort, patients were divided into two subgroups: no/low‐dose loop diuretic and high‐dose loop diuretic. Primary outcome was 5 year all‐cause mortality. Among the 397 patients included, 227 (57%) were treated with loop diuretics. Median daily furosemide equivalent dose was 25 mg, and accordingly patients were divided in no/low dose (i.e. ≤25 mg, n = 257, 65%) vs. high dose (i.e. >25 mg, n = 140, 35%). Patients in the high‐dose group were older, more likely to have comorbidities, and had a more severe disease according to the ESC/ERS risk category. Crude 5 year survival was significantly shorter in patients in the high‐dose group, but after adjustment for age, sex, and risk category, high loop diuretic dose was not significantly associated with the primary outcome. Conclusions Use of high dose of loop diuretics in PAH is associated with a higher burden of comorbidities, more severe disease, and worse survival. However, in PAH, the need of high loop diuretic dose is a marker of disease severity and not an independent prognostic factor.

Abstract 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+ ν ejj at the LHC in a tri-boson phase space. We evaluate the three LO contributions, namely the O $$ \mathcal{O} $$ (α 6), which contains the genuine tri-boson signature, along with the O $$ \mathcal{O} $$ (α s α 5) and O $$ \mathcal{O} $$ ( α s 2 $$ {\alpha}_{\textrm{s}}^2 $$ α 4), and the two O $$ \mathcal{O} $$ (α 7) and O $$ \mathcal{O} $$ (α s α 6) 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 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).

Pancreatic cystic lesions (PCLs) have been increasingly identified in recent years, encompassing a wide spectrum ranging from benign non-evolutive to malignant invasive lesions. Despite various clinical, laboratory, imaging, endoscopic ultrasound, and cytohistological features that may aid clinicians in the complex differential diagnosis of PCLs, only a few pathognomic signs distinctive to specific PCLs have been identified. Although rarely encountered, their proper recognition is crucial for the appropriate management of PCLs. The aim of our review is to extensively discuss and illustrate pathognomic signs in the setting of PCLs.

The present study is aimed at the characterization of artifacts excavated in the necropolis surrounding the mausoleum of the Aga Khan in Aswan (Egypt), as part of the Mummies Investigations Anthropological & Scientific West Aswan Necropolis (MIASWAN) project. Four cartonnages and some pottery shards were investigated on-site by means of non-destructive and micro-destructive techniques, such as attenuated total reflection/Fourier transform infrared spectroscopy (ATR/FTIR) and visible reflectance spectroscopy Vis-RS). Thanks to the use of these techniques, several pigments employed in the creation of the artifacts were identified. Due to the impossibility of transporting the investigated objects out of Egypt, a first-ever on-site characterization of the artifacts from this important excavation was carried out through scientific methodologies. These extreme conditions made the use of analytical instrumentation very challenging. Nevertheless, several characteristic pigments and hues were successfully identified.

In the literature, finite mixture models were described as linear combinations of probability distribution functions having the form $ f(x) = \Lambda \sum\limits_{i = 1}^n w_i f_i(x) $, $ x \in \mathbb{R} $, where $ w_i $ were positive weights, $ \Lambda $ was a suitable normalising constant, and $ f_i(x) $ were given probability density functions. The fact that $ f(x) $ is a probability density function followed naturally in this setting. Our question was: if we removed the sign condition on the coefficients $ w_i $, how could we ensure that the resulting function was a probability density function?The solution that we proposed employed an algorithm which allowed us to determine all zero-crossings of the function $ f(x) $. Consequently, we determined, for any specified set of weights, whether the resulting function possesses no such zero-crossings, thus confirming its status as a probability density function.In this paper, we constructed such an algorithm which was based on the definition of a suitable sequence of functions and that we called a generalized Budan-Fourier sequence; furthermore, we offered theoretical insights into the functioning of the algorithm and illustrated its efficacy through various examples and applications. Special emphasis was placed on generalized Gaussian mixture densities.

Over the last two decades, we have witnessed great advancements in our understanding of the immunological pathways of asthma, leading to the development of targeted therapies, such as biologic drugs, that have radically and definitively changed the clinical outcomes of severe asthma. Despite the numerous therapeutic options available, ~4–10% of all people with asthma have severe or uncontrolled asthma, associated with an increased risk of developing chronic oral corticosteroid use, fixed airflow limitation, exacerbations, hospitalization and, finally, increased healthcare costs. The new concept of disease modification in asthma comes from the evolution of asthma management, which encompasses phenotyping patients with different inflammatory endotypes characterizing the disease, followed by the advent of more effective therapies capable of targeting the proximal factors of airway inflammation. This treat-to-target approach aims to achieve remission of the disease. Because the novel treatment paradigm for severe asthma with the advent of biologic therapies is no longer clinical control but rather clinical remission – a step closer to the concept of cure – a deeper and more accurate understanding of the critical causal mechanisms and endotypes of asthma is necessary to achieve the goal of clinical remission, which has the potential to generate real life-changing benefits for patients. This review aims to frame the evolution of the debated concept of clinical remission and provide clinicians with insights that may be helpful in achieving remission in the greatest number of patients.

Abstract 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 Background Glioblastoma (GBM) stands as the most prevalent and aggressive form of adult gliomas. Despite the implementation of intensive therapeutic approaches involving surgery, radiation, and chemotherapy, Glioblastoma Stem Cells contribute to tumor recurrence and poor prognosis. The induction of Glioblastoma Stem Cells differentiation by manipulating the transcriptional machinery has emerged as a promising strategy for GBM treatment. Here, we explored an innovative approach by investigating the role of the depolarized resting membrane potential (RMP) observed in patient-derived GBM sphereforming cell (GSCs), which allows them to maintain a stemness profile when they reside in the G0 phase of the cell cycle. Methods We conducted molecular biology and electrophysiological experiments, both in vitro and in vivo, to examine the functional expression of the voltage-gated sodium channel (Nav) in GSCs, particularly focusing on its cell cycle-dependent functional expression. Nav activity was pharmacologically manipulated, and its effects on GSCs behavior were assessed by live imaging cell cycle analysis, self-renewal assays, and chemosensitivity assays. Mechanistic insights into the role of Nav in regulating GBM stemness were investigated through pathway analysis in vitro and through tumor proliferation assay in vivo. Results We demonstrated that Nav is functionally expressed by GSCs mainly during the G0 phase of the cell cycle, suggesting its pivotal role in modulating the RMP. The pharmacological blockade of Nav made GBM cells more susceptible to temozolomide (TMZ), a standard drug for this type of tumor, by inducing cell cycle re-entry from G0 phase to G1/S transition. Additionally, inhibition of Nav substantially influenced the self-renewal and multipotency features of GSCs, concomitantly enhancing their degree of differentiation. Finally, our data suggested that Nav positively regulates GBM stemness by depolarizing the RMP and suppressing the ERK signaling pathway. Of note, in vivo proliferation assessment confirmed the increased susceptibility to TMZ following pharmacological blockade of Nav. Conclusions This insight positions Nav as a promising prognostic biomarker and therapeutic target for GBM patients, particularly in conjunction with temozolomide treatment.

ABSTRACT: This study aimed to assess the effect of bulk tank milk (BTM), waste milk (WM), and pasteurized waste milk (PWM) on nutrient digestibility, ruminal and cecal fermentation, gastrointestinal tract (GIT) development, and antimicrobial resistance of fecal Escherichia coli from dairy calves at 2 periods (30 and 60 d of age). Calves were grouped according to BW, serum protein levels, and breed composition. Three treatments were included: BTM (n = 21), WM from cows under antibiotic treatment (n = 21), and PWM (WM submitted to HTST pasteurization; n = 21). A total of 63 calves were used, of which 18 animals (n = 6 per treatment) were evaluated in the period of 4 to 30 d, and 45 (n = 15 per treatment) from 4 to 60 d. During the experimental period, a daily intake of 6 L of milk was divided into 2 equal meals, with ad libitum access to water and starter. Milk and feed intakes were recorded daily. Apparent total-tract digestibility and nitrogen balance were conducted from 25 to 29 d of age (n = 6) and from 53 to 57 d of age (n = 15). Animals were slaughtered at 30 ± 1 and 60 ± 1 d of age for the assessment of ruminal and cecal fermentation and GIT development. Antimicrobial susceptibility testing was conducted at 1, 30, and 60 d of age (n = 15/treatment). Statistical analysis used a linear mixed-effects model for continuous outcomes and generalized linear models for single measurements (R software). Treatments WM and PWM had lower rumen pH, higher ruminal acetate concentration, larger reticulorumen and liver, and a higher prevalence of fecal-resistant E. coli compared with BTM at both 30 and 60 d. Up to 60 d, both BTM and WM treatments exhibited higher digestibility of ether extract and gross energy compared with the PWM, whereas WM and PWM treatments showed increased nitrogen intake and retention compared with the BTM treatment. These findings suggest that pasteurization of WM negatively affects nutrient digestibility and calf performance, while also affecting rumen development. Additionally, the use of milk containing antibiotic residue leads to the selection of resistant E. coli in the GIT over time.

Abstract 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 + ν ℓ + 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 $$ \mathcal{O}\left({\alpha}^6\right) $$ , we complement our results with O α s α 5 $$ \mathcal{O}\left({\alpha}_{\textrm{s}}{\alpha}^5\right) $$ and O α s 2 α 4 $$ \mathcal{O}\left({\alpha}_{\textrm{s}}^2{\alpha}^4\right) $$ for inclusive predictions. At O α 6 $$ \mathcal{O}\left({\alpha}^6\right) $$ 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 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.

The uncertainty of hydrological forecasts is strongly related to the uncertainty of the rainfall field due to the nonlinear relationship between the spatio-temporal pattern of rainfall and runoff. Rain gauges are typically considered to provide reference data to rebuild precipitation fields. However, due to the density and the distribution variability of the rain gauge network, the rebuilding of the precipitation field can be affected by severe errors which compromise the hydrological simulation output. On the other hand, retrievals obtained from remote sensing observations provide spatially resolved precipitation fields, improving their representativeness. In this regard, the comparison between simulated and observed river flow discharge is crucial for assessing the effectiveness of merged precipitation data in enhancing the model's performance and its ability to realistically simulate hydrological processes. This paper aims to investigate the hydrological impact of using the merged rainfall fields from the Italian rain gauge network and the NASA Global Precipitation Measurement (GPM) IMERG precipitation product. One aspect is to highlight the benefits of applying the cellular automata algorithm to pre-process input data in order to merge them and reconstruct an improved version of the precipitation field. The cellular automata approach is evaluated in the Tanaro River basin, one of the tributaries of the Po River in Italy. As this site is characterized by the coexistence of a variety of natural morphologies, from mountain to alluvial environments, as well as the presence of significant civil and industrial settlements, it makes it a suitable case study to apply the proposed approach. The latter has been applied over three different flood events that occurred from November to December 2014. The results confirm that the use of merged gauge–satellite data using the cellular automata algorithm improves the performance of the hydrological simulation, as also confirmed by the statistical analysis performed for 17 selected quality scores.

Abstract 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.

Climate change contributes to the increased frequency and intensity of wildfires globally, with significant impacts on society and the environment. However, our understanding of the global distribution of extreme fires remains skewed, primarily influenced by media coverage and regionalised research efforts. This inaugural State of Wildfires report systematically analyses fire activity worldwide, identifying extreme events from the March 2023–February 2024 fire season. We assess the causes, predictability, and attribution of these events to climate change and land use and forecast future risks under different climate scenarios. During the 2023–2024 fire season, 3.9×106 km2 burned globally, slightly below the average of previous seasons, but fire carbon (C) emissions were 16 % above average, totalling 2.4 Pg C. Global fire C emissions were increased by record emissions in Canadian boreal forests (over 9 times the average) and reduced by low emissions from African savannahs. Notable events included record-breaking fire extent and emissions in Canada, the largest recorded wildfire in the European Union (Greece), drought-driven fires in western Amazonia and northern parts of South America, and deadly fires in Hawaii (100 deaths) and Chile (131 deaths). Over 232 000 people were evacuated in Canada alone, highlighting the severity of human impact. Our analyses revealed that multiple drivers were needed to cause areas of extreme fire activity. In Canada and Greece, a combination of high fire weather and an abundance of dry fuels increased the probability of fires, whereas burned area anomalies were weaker in regions with lower fuel loads and higher direct suppression, particularly in Canada. Fire weather prediction in Canada showed a mild anomalous signal 1 to 2 months in advance, whereas events in Greece and Amazonia had shorter predictability horizons. Attribution analyses indicated that modelled anomalies in burned area were up to 40 %, 18 %, and 50 % higher due to climate change in Canada, Greece, and western Amazonia during the 2023–2024 fire season, respectively. Meanwhile, the probability of extreme fire seasons of these magnitudes has increased significantly due to anthropogenic climate change, with a 2.9–3.6-fold increase in likelihood of high fire weather in Canada and a 20.0–28.5-fold increase in Amazonia. By the end of the century, events of similar magnitude to 2023 in Canada are projected to occur 6.3–10.8 times more frequently under a medium–high emission scenario (SSP370). This report represents our first annual effort to catalogue extreme wildfire events, explain their occurrence, and predict future risks. By consolidating state-of-the-art wildfire science and delivering key insights relevant to policymakers, disaster management services, firefighting agencies, and land managers, we aim to enhance society's resilience to wildfires and promote advances in preparedness, mitigation, and adaptation. New datasets presented in this work are available from https://doi.org/10.5281/zenodo.11400539 (Jones et al., 2024) and https://doi.org/10.5281/zenodo.11420742 (Kelley et al., 2024a).

Abstract As major terrestrial carbon sinks, forests play an important role in mitigating climate change. The relationship between the seasonal uptake of carbon and its allocation to woody biomass remains poorly understood, leaving a significant gap in our capacity to predict carbon sequestration by forests. Here, we compare the intra-annual dynamics of carbon fluxes and wood formation across the Northern hemisphere, from carbon assimilation and the formation of non-structural carbon compounds to their incorporation in woody tissues. We show temporally coupled seasonal peaks of carbon assimilation (GPP) and wood cell differentiation, while the two processes are substantially decoupled during off-peak periods. Peaks of cambial activity occur substantially earlier compared to GPP, suggesting the buffer role of non-structural carbohydrates between the processes of carbon assimilation and allocation to wood. Our findings suggest that high-resolution seasonal data of ecosystem carbon fluxes, wood formation and the associated physiological processes may reduce uncertainties in carbon source-sink relationships at different spatial scales, from stand to ecosystem levels.

Abstract Anisotropic transport properties have been assessed in a number of cuprate superconductors, providing evidence for a nematic state. We have recently shown that in ultra-thin YBa2Cu3O7−δ films, where nematicity is induced via strain engineering, there is a suppression of charge density wave scattering along the orthorhombic a-axis and a concomitant enhancement of strange metal behavior along the b-axis. Here we develop a microscopic model, that is based on the strong interaction between the substrate facets and the thin film, to account for the unconventional phenomenology. Based on the atomic force microscopy imaging of the substrates’ surface, the model is able to predict the absence (presence) of nematicity and the resulting transport properties in films grown on SrTiO3 (MgO) substrates. Our result paves the way to new tuning capabilities of the ground state of high-temperature superconductors by substrate engineering.

Abstract The multi-staged XENON program at INFN Laboratori Nazionali del Gran Sasso aims to detect dark matter with two-phase liquid xenon time projection chambers of increasing size and sensitivity. The XENONnT experiment is the latest detector in the program, planned to be an upgrade of its predecessor XENON1T. It features an active target of 5.9 tonnes of cryogenic liquid xenon (8.5 tonnes total mass in cryostat). The experiment is expected to extend the sensitivity to WIMP dark matter by more than an order of magnitude compared to XENON1T, thanks to the larger active mass and the significantly reduced background, improved by novel systems such as a radon removal plant and a neutron veto. This article describes the XENONnT experiment and its sub-systems in detail and reports on the detector performance during the first science run.

This case report explores the therapeutic impact of SMARCA4 loss in a 63-year-old female patient with a history of smoking, hypertension, hypercholesterolemia, and prior surgeries for breast and pancreatic carcinomas, who presented with a new pulmonary nodule. On February 23, 2024, a CT scan identified a solid pulmonary nodule in the right lower lobe. A PET scan confirmed the nodule's metabolic activity. By May 8, 2024, follow-up imaging revealed disease progression and central cavitation in the nodule. Following admission on June 14, 2024, the patient underwent a multidisciplinary evaluation, and a lobectomy of the right lower lobe was performed. Pre-operative assessments indicated good general health and no respiratory distress. Post-surgical histology demonstrated a SMARCA4-deficient non-small cell lung cancer with loss of Brahma-related gene 1. Immunohistochemical analyses showed positive expressions of Cytokeratin-7, focal cytoplasmic positivity for Hepar-1 and loss of BRG-1. The surgery successfully removed the neoplasm, and the patient remained alive and disease-free post-operation. The follow-up plan includes tri-annual visits with contrast-enhanced chest and abdomen CT scans to monitor for recurrence. The case underscores the significance of identifying SMARCA4 deficiencies in NSCLC and advocating for tailored therapeutic strategies. Enhanced awareness and understanding of SMARCA4-deficient NSCLC can guide future treatment protocols and improve patient outcomes.

ABSTRACT Objective: To evaluate the incidence rates of mycobacterial infections in silicosis patients with systemic autoimmune rheumatic disease (ARD). Methods: This was a retrospective cohort of silicosis patients between January of 1999 and December of 2023. We compared the incidence of tuberculosis and nontuberculous mycobacterial disease (NTM) in patients with silicosis with and without ARD. We also compared the tuberculosis incidence in the overall cohort with general Brazilian population estimates. Results: The study comprised 369 silicosis patients, of whom 35 (9.5%) had ARD. Having ARD did not affect the cumulative incidence of mycobacterial diseases. The risk of tuberculosis was higher in the cohort when compared with that in the adult Brazilian male population (age-adjusted incidence rate ratio = 20.46; 95% CI 14.89-28.13). Conclusions: In this cohort of patients with silicosis, ARD was not associated with the incidence of mycobacterial diseases.

La red de caminos prehispánicos utilizados por los incas se ha propuesto como el resultado de un proyecto político dirigido por ellos, aunque basado en experiencias anteriores. En esta narrativa, la red vial fue producto de la planificación estatal inca y tenía principalmente un fin administrativo. Esta interpretación es influyente y se usa para sostener la narrativa del Estado peruano moderno que aprende de las lecciones del pasado y es heredero del proyecto político inca. Sin embargo, varios autores argumentan que esta interpretación simplifica el complejo y gradual desarrollo de la red, que involucró a diversos actores más allá de las instituciones políticas centralizadas, reclamando la necesidad de identificar la agencia de las comunidades locales. En este contexto, la revaloración de los caminos prehispánicos puede generar dominación o ser un mecanismo de integración y reestructuración social que promueva las identidades locales. Este artículo utiliza los conceptos de ruta y trazo para analizar las redes viales en la región de Piura, proporcionando una perspectiva regional a largo plazo. Cuestiona las narrativas dominantes centradas en los incas, destacando la importancia local de los caminos y demostrando la continuidad de la infraestructura, arraigada en experiencias diarias que trascienden el control estatal.

Background: Allergic rhinitis (AR) is a highly prevalent disease. We aimed to assess the symptoms that physicians who see patients with AR perceive as the most bothersome in their patients. Methods: We performed a cross-sectional study based on an online questionnaire sent to all members of the Allergic Rhinitis and its Impact on Asthma (ARIA) initiative. The survey included questions on the physicians' perceptions of patients’ AR symptoms as well as of their own AR symptoms. Results: Among 401 respondents, 155 (38.7%) reported having AR. ARIA members reported nasal symptoms to be the most frequent (89.7%) and bothersome (80.0%) symptoms experienced by themselves. Likewise, nasal symptoms were reported by ARIA members as the most frequent (94.8% in members with AR vs 96.0% in members without AR) and bothersome (57.0% in members with AR vs 67.9% in members without AR) in their patients. We found a significant association (p = 0.001) between physicians’ own symptoms and those perceived as the most bothersome in their patients. Conclusion: Physicians perceive nasal symptoms to be the most frequent and the most bothersome symptoms in AR patients. The physicians' personal experiences with AR may influence their perception of patients’ symptoms.

Not available.

Diabetes mellitus (DM) is one of the most prevalent cardiovascular risk factors in the general population, being associated with high morbidity and socioeconomic burden. Diabetic cardiomyopathy (DCM) is a non-negligible complication of DM, whose pathophysiological fundaments are the altered cardiac metabolism, the hyperglycemia-triggered formation of advanced glycation end-products (AGEs) and the inflammatory milieu which are typical in diabetic patients. These metabolic abnormalities lead to cardiomyocytes apoptosis, interstitial fibrosis and mechanical cardiac dysfunction, which can be identified with non-invasive imaging techniques, like echocardiography and cardiac magnetic resonance. This review aims to: 1) describe the major imaging features of DCM; 2) highlight how early identification of DCM-related anatomical and functional remodeling might allow patients’ therapy optimization and prognosis improvement.

Fertility preservation (FP) is an important aspect of the treatment of young women diagnosed with serous borderline ovarian tumors (SBOT), with fertility sparing surgery recommended when possible. Concurrent treatment with aromatase inhibitor letrozole during ovarian stimulation (OS) could be used in women with hormone-sensitive breast cancer, but very little is known in gynecological tumors. Here, we report the cases of 2 young nulliparous women with early stage SBOT who underwent successful OS with letrozole. Patient 1 is 22-years old, FIGO IIB. She had a bilateral ovarian recurrence 5 months after the first surgery. She underwent OS with letrozole (four oocytes were collected and vitrified), followed by cytoreduction. The patient is in complete remission since 2 years. Patient 2 is 27-years old, FIGO IC3, treated by right adnexectomy. Ten months after surgery, she was in complete remission. OS with letrozole was performed and 4 oocytes were retrieved, resulting in 2 blastocysts that were cryopreserved. She had a successful pregnancy after in-vitro fertilization. She underwent a delivery via C-Section for obstetrical reasons that revealed a macroscopic suspicious lesion on the left ovary. Cystectomy was performed during C-section, confirming tumor recurrence. She underwent a second pregnancy uneventfully. During the second C-section, a partial cystectomy and multiples peritoneal biopsies were performed revealing tumor recurrence limited to the left ovary. She underwent left adnexectomy two months after C-Section without any recurrence. In conclusion, our case report described successful oocytes cryopreservation, without changes in the appearance of ovarian cysts, in nulliparous women with early-stage SBOT who underwent OS with simultaneous administration of letrozole.

Wild leafy vegetables, historically vital for Alpine biodiversity and nutrition during hardship, are regaining importance due to the demand for healthy and sustainable food. This study evaluated mineral and phytochemical compositions of eight species: Achillea millefolium, Alchemilla xanthochlora, Bistorta officinalis, Blitum bonus-henricus, Phyteuma betonicifolium, Plantago lanceolata, Silene vulgaris, Taraxacum sect. Taraxacum. Total trace element concentrations ranged from 26 mg kg−1 (T. officinalis) to 92 mg kg−1 (B. officinalis), and potential toxic elements were below legal limits. The sum of the phenolic compounds analysed ranged from 155.30 mg GAE 100 g−1 FW (A. millefolium) to 1200.38 mg GAE 100 g−1 FW (A. xanthochlora). Flavanols were the most abundant phenolic class, but cinnamic acids, flavonols, benzoic acids and vitamin C also showed high values in the analysed species, contributing to high antioxidant activity (from 0.59 μmol TE g−1 FW in A. millefolium to 149.39 μmol TE g−1 FW in A. xanthochlora for DPPH). Overall, A. xanthochlora stood out for its richness in phenolic compounds. These findings underscore wild vegetables potential as functional foods, offering bioactive compounds comparable to or exceeding cultivated plants. Emphasizing preservation of traditional diets and rural innovation, this research supports the integration of wild leafy vegetables into contemporary nutrition strategies.

ABSTRACTChronic obstructive pulmonary disease (COPD) is a common chronic respiratory illness in older adults. A major cause of COPD-related morbidity and mortality is acute exacerbation of COPD (AECOPD). Bacteria in the lungs play a role in exacerbation development, and the most common pathogen is non-typeable Haemophilus influenzae (NTHi). A vaccine to prevent AECOPD containing NTHi surface antigens was tested in a clinical trial. This study measured IgG and IgA against NTHi vaccine antigens in sputum. Sputum samples from 40 COPD patients vaccinated with the NTHi vaccine were collected at baseline and 30 days after the second dose. IgG and IgA antibodies against the target antigens and albumin were analyzed in the sputum. We compared antibody signals before and after vaccination, analyzed correlation with disease severity and between sputum and serum samples, and assessed transudation. Antigen-specific IgG were absent before vaccination and present with high titers after vaccination. Antigen-specific IgA before and after vaccination were low but significantly different for two antigens. IgG correlated between sputum and serum, and between sputum and disease severity. Sputum albumin was higher in patients with severe COPD than in those with moderate COPD, suggesting changes in transudation played a role. We demonstrated that immunization with the NTHi vaccine induces antigen-specific antibodies in sputum. The correlation between IgG from sputum and serum and the presence of albumin in the sputum of severe COPD patients suggested transudation of antibodies from the serum to the lungs, although local IgG production could not be excluded.Clinical Trial Registration: NCT02075541

Identification of the diverse animal hosts responsible for spill-over events from animals to humans is crucial for comprehending the transmission patterns of emerging infectious diseases, which pose significant public health risks. To better characterize potential animal hosts of Lassa virus (LASV), we assessed domestic and non-domestic animals from 2021–2022 in four locations in southern Nigeria with reported cases of Lassa fever (LF). Birds, lizards, and domestic mammals (dogs, pigs, cattle and goats) were screened using RT-qPCR, and whole genome sequencing was performed for lineage identification on selected LASV positive samples. Animals were also screened for exposure to LASV by enzyme-linked immunosorbent assay (ELISA). Among these animals, lizards had the highest positivity rate by PCR. Genomic sequencing of samples in most infected animals showed sub-lineage 2 g of LASV. Seropositivity was highest among cattle and lowest in pigs. Though the specific impact these additional hosts may have in the broader virus-host context are still unknown – specifically relating to pathogen diversity, evolution, and transmission – the detection of LASV in non-rodent hosts living in proximity to confirmed human LF cases suggests their involvement during transmission as potential reservoirs. Additional epidemiological data comparing viral genomes from humans and animals, as well as those circulating within the environment will be critical in understanding LASV transmission dynamics and will ultimately guide the development of countermeasures for this zoonotic health threat.

Background: COVID-19 accelerated federally qualified health centers’ use of telemental health. However, factors associated with telemental health service delivery remain unclear. We examined telemental health delivery by clinician type and mental health workforce composition across the U.S. to understand how staffing and other organizational characteristics are related to telemental health delivery at health centers. Methods: Using data from the 2021 Uniform Data System, we characterized the proportion of mental health care delivered via elemental (i.e., virtual visits) at health centers in the U.S. that received HRSA grant funding (n = 1,270) overall and by state and clinician type. Then, we conducted multivariate beta regression analyses to assess the proportion of mental health visits delivered via telemental health at health centers as a function of mental health workforce composition, while adjusting for health center size, patient mix, and state. Results: In 2021, health centers delivered 43% of their mental health visits via telemental health, with significant variation by state and clinician type. On average, the proportion of mental health visits delivered via telemental health was greater among psychiatrists (61%, P

Abstract Reintroductions are often needed to recover carnivore populations and restore ecological processes. Felids are common subjects of reintroduction efforts, but published population models informing felid reintroduction plans are uncommon, and poor planning has sometimes caused issues in felid reintroduction programs. In the United States, ocelots (Leopardus pardalis pardalis) are classified as endangered, and recovery requires population expansion into historic habitat. A multi‐organization effort is underway to establish a new ocelot population in Texas by releasing ocelots into an area of 478 km2 of suitable habitat in ocelots' historic but now unoccupied range. In this study, we used population viability analyses to compare different ocelot reintroduction strategies for the identified reintroduction area. Based on a potential ocelot breeding program's limitations, we modeled reintroduction using a founding population of no more than six ocelots and no more than four ocelots released per year for no more than 15 subsequent years. Within these limitations, we assessed projected population abundances and extinction risks after 30 years for 20 different reintroduction strategies. We found that long‐term releases are necessary to establish a viable population; under conservative model assumptions, releasing six ocelots in the initial year and then releasing four individuals annually for an additional 10–15 years is necessary for attaining a projected population greater than 36.62 ocelots (baseline) with

Background: High incidence mpox rates suggest asymptomatic individuals may contribute to virus transmission. We undertook this study to assess the seroprevalence of IgG anti-MPXV in a cohort of asymptomatic PLWH, to analyze the size of the phenomenon of asymptomatic infections. Materials and methods: From October 2022 to March 2023 we serially collected serum samples from PLWH attending our Clinic. IgG against MPXV have been assessed on stored cryopreserved samples with an ELISA. Only people with no previous reported vaccine against smallpox or mpox nor previous clinical manifestations consistent with a mpox diagnosis were included. Results: 285 PLWH were included. Twenty-one participants tested positive for IgG anti MPXV (7.37 %, 95 % CI 4.62–11.0). Seropositivity was predominant in male (15/285, 71.4) with a small fraction of female (6/285,28.6 %) and PWID (1/285,4.8 %). Conclusions: Our findings suggest the possibility of an asymptomatic course of the mpox infection even in populations beyond traditional high-risk groups.

Objetiva-se criticar as pedagogias hegemônicas e realizar a defesa dos fundamentos teórico-práticos da Pedagogia Histórico-Crítica para o ensino das Ciências Humanas. Parte-se do pressuposto de que na luta política, como disputa por hegemonia, as classes sociais almejam o controle dos meios de produção material, de todo o complexo cultural; e discutem-se as pedagogias corporativas e sua influência na educação brasileira. Apresentam-se os fundamentos pedagógico-críticos que norteiam os currículos escolares e contribuem para a inserção crítica das novas gerações na vida pública. Por meio de análise bibliográfica e documental, almeja-se subsidiar a formação de professores e estudantes interessados no estudo da Pedagogia Histórico-Crítica, a fim de elaborar currículos e propostas político-pedagógicas contra-hegemônicas.

Several endotypes of severe asthma with predominantly type 2 inflammation can be distinguished by the immune pathways driving the inflammatory processes. However, in the absence of type 2 inflammation, asthma is less clearly defined and is generally associated with poor responses to conventional anti-asthmatic therapies. Studies have shown that disruption of the epithelial barrier triggers inflammatory responses and increases epithelial permeability. A key aspect of this process is that epithelial cells release alarmin cytokines, including interleukin (IL)-25, IL-33, and thymic stromal lymphopoietin (TSLP), in response to allergens and infections. Among these cytokines, TSLP has been identified as a potential therapeutic target for severe asthma, leading to the development of a new biologic, tezepelumab (TZP). By blocking TSLP, TZP may produce wide-ranging effects. Based on positive clinical trial results, TZP appears to offer a promising, safe, and effective treatment approach. This narrative review examines the evidence for treating severe asthma with TZP, analyses clinical trial findings, and provides clinicians with practical insights into identifying patients who may respond best to this novel biologic therapy.

BackgroundExperiencing a traumatic event can significantly impact mental and emotional well-being. Social media platforms offer spaces for sharing stories, seeking support, and accessing psychoeducation. TikTok (ByteDance), a rapidly growing social media platform, is increasingly used for advice, validation, and information, although the content of this requires further study. Research is particularly needed to better understand TikTok content relating to trauma and the potential implications for young viewers, considering the distressing nature of the subject and the possibility of users experiencing vicarious trauma through exposure to these videos. ObjectiveThis study aims to explore the content of trauma-related videos on TikTok, focusing on hashtags related to trauma. Specifically, this study analyzes how TikTok videos present information, advice, stories, and support relating to trauma. MethodsA quantitative cross-sectional descriptive content analysis was performed on TikTok in December 2022. A total of 5 hashtags related to trauma were selected: #trauma, #traumatized, #traumatok, #traumatic, and #traumabond, with the top 50 videos from each hashtag analyzed (total N=250 videos). A standardized codebook was developed inductively to analyze the content of the videos, while an existing generic codebook was used to collect the video features (eg, age of people in the video) and metadata (likes, comments, and shares) for each video. ResultsA total of 2 major content themes were identified, which were instructional videos (54/250, 21.6%) and videos disclosing personal stories (168/250, 67.3%). The videos garnered significant engagement, with a total of 296.6 million likes, 2.3 million comments, and 4.6 million shares, indicating that users find this content engaging and useful. Alarmingly, only 3.7% (9/250) of videos included a trigger warning, despite many featuring highly distressing stories that young people and those with trauma may be exposed to. ConclusionsThe study highlights the potential risks of vicarious trauma due to trauma dumping without trigger warnings on TikTok, and the need for further research to assess the accuracy of advice and information in these videos. However, it also underscores the platform’s potential to foster social connections, provide validation, and reduce stigma around mental health issues. Public health professionals should leverage social media to disseminate accurate mental health information, while promoting user education and content moderation to mitigate potential harms. People often use social media, such as TikTok to share advice, stories, and support around mental health, including their experiences with trauma. Out of 250 videos, most were either giving advice (54/250, 21.6%) or sharing personal experiences (168/250, 67.3%). The study found many videos lacked warnings about upsetting content, which could potentially harm young viewers or people suffering from trauma. While TikTok can help people feel connected and reduce the stigma around mental health, it is important to seek support from professionals when needed.

According to the FAO/WHO guidelines, selection of probiotics requires the assessment of survival under gastrointestinal stress and adhesion to human epithelial cells. These attributes were evaluated on Akkermansia muciniphila ATCC BAA-835 simulating the gastrointestinal transit (GIT) immediately followed by adhesion to human intestinal cell lines (CaCo2, HT-29, and HT-29-MTX) as an alternative approach to in vitro methods performed with fresh cells in each trial. The survival rate after GIT, as determined by plate counts and fluorescent probes, was significantly higher for A. muciniphila (about 8 Log CFU/mL) than for the probiotic Lacticaseibacillus rhamnosus GG ATCC 53103 (about 3 Log CFU/mL). The use of Live/Dead assay highlighted that A. muciniphila forms cell aggregates in the gastric phase as protective mechanism, explaining its high viability in the intestine. The rate of adhesion to human cell lines was always lower for strains tested after simulated GIT than for strains that did not undergo simulated GIT. Akkermansia muciniphila exhibited significantly higher adhesion than Lbs. rhamnosus GG, particularly to the mucus-secreting HT-29-MTX cells across a range of concentrations (2–8 Log CFU/mL). Finally, the bioinformatic analysis of A. muciniphila proteome confirmed the Amuc_1434 as a potential factor in binding to the human MUC2 protein.

Background: Despite the well-known efficacy of anti-COVID-19 vaccines in preventing morbidity and mortality, several vaccinated individuals are diagnosed with SARS-CoV-2 breakthrough infection, which might require hospitalisation. This multicentre, observational, and retrospective study aimed to investigate the clinical characteristics and outcomes of vaccinated vs. non-vaccinated patients, both hospitalised with SARS-CoV-2 infection in 3 major hospitals in Northern Italy. Methods: Data collection was retrospective, and paper and electronic medical records of adult patients with a diagnosed SARS-CoV-2 infection were pseudo-anonymised and analysed. Vaccinated and non-vaccinated individuals were manually paired, using a predetermined matching criterion (similar age, gender, and date of hospitalisation). Demographic, clinical, treatment, and outcome data were compared between groups differing by vaccination status using Pearson’s Chi-square and Mann-Whitney tests. Moreover, multiple logistic regression analyses were performed to assess the impact of vaccination status on ICU admission or intra-hospital mortality. Results: Data from 360 patients were collected. Vaccinated patients presented with a higher prevalence of relevant comorbidities, like kidney replacement therapy or haematological malignancy, despite a milder clinical presentation at the first evaluation. Non-vaccinated patients required intensive care more often than their vaccinated counterparts (8.8% vs. 1.7%, p = 0.002). Contrariwise, no difference in intra-hospital mortality was observed between the two groups (19% vs. 20%, p = 0.853). These results were confirmed by multivariable logistic regressions, which showed that vaccination was significantly associated with decreased risk of ICU admission (aOR=0.172, 95%CI: 0.039–0.542, p = 0.007), but not of intra-hospital mortality (aOR=0.996, 95%CI: 0.582–1.703, p = 0.987). Conclusions: This study provides real-world data on vaccinated patients hospitalised with COVID-19 in Northern Italy. Our results suggest that COVID-19 vaccination has a protective role in individuals with higher risk profiles, especially regarding the need for ICU admission. These findings contribute to our understanding of SARS-CoV-2 infection outcomes among vaccinated individuals and emphasise the importance of vaccination in preventing severe disease, particularly in those countries with lower first-booster uptake rates.

Abstract Background Despite recent financial and policy support for harm reduction in the USA, information on the types of workers within organizations who design, implement, and actualize harm reduction services remains nascent. Little is known about how variability in the harm reduction workforce impacts referrals and linkages to other community supports. This exploratory mixed-methods study asked: (1) Who constitutes the harm reduction workforce? (2) Who provides behavioral health services within harm reduction organizations? (3) Are referral services offered and by whom? (4) Do referrals differ by type of harm reduction worker? Methods Purposive sampling techniques were used to distribute an electronic survey to U.S.-based harm reduction organizations. Descriptive statistics were conducted. Multivariate binary logistic regression models examined the associations (a) between the odds of the referral processes at harm reduction organizations and (b) between the provision of behavioral health services and distinct types of organizational staff. Qualitative data were analyzed using a hybrid approach of inductive and thematic analysis. Results Data from 41 states and Washington, D.C. were collected (N = 168; 48% response rate). Four primary types of workers were identified: community health/peer specialists (87%); medical/nursing staff (55%); behavioral health (49%); and others (34%). About 43% of organizations had a formal referral process; among these, only 32% had follow-up protocols. Qualitative findings highlighted the broad spectrum of behavioral health services offered and a broad behavioral health workforce heavily reliant on peers. Unadjusted results from multivariate models found that harm reduction organizations were more than 5 times more likely (95% CI [1.91, 13.38]) to have a formal referral process and 6 times more likely (95% CI [1.74, 21.52]) to have follow-up processes when behavioral health services were offered. Organizations were more than two times more likely (95% CI [1.09, 4.46]) to have a formal referral process and 2.36 (95% CI [1.11, 5.0]) times more likely to have follow-up processes for referrals when behavioral health providers were included. Conclusions The composition of the harm reduction workforce is occupationally diverse. Understanding the types of services offered, as well as the workforce who provides those services, offers valuable insights into staffing and service delivery needs of frontline organizations working to reduce morbidity and mortality among those who use substances. Workforce considerations within U.S.-based harm reduction organizations are increasingly important as harm reduction services continue to expand.

Abstract Introduction Cefiderocol is a siderophore cephalosporin showing activity against various carbapenem-resistant Gram-negative bacteria (CR-GNB). No data currently exist about real-world use of cefiderocol in terms of types of therapy (e.g., empirical or targeted, monotherapy or combined regimens), indications, and patient characteristics. Methods In this multicenter, prospective study, we aimed at describing the use of cefiderocol in terms of types of therapy, indications, and patient characteristics. Results Cefiderocol was administered as empirical and targeted therapy in 27.5% (55/200) and 72.5% (145/200) of cases, respectively. Overall, it was administered as monotherapy in 101/200 cases (50.5%) and as part of a combined regimen for CR-GNB infections in the remaining 99/200 cases (49.5%). In multivariable analysis, previous isolation of carbapenem-resistant Acinetobacter baumannii odds ratio (OR) 2.56, with 95% confidence interval (95% CI) 1.01–6.46, p = 0.047] and previous hematopoietic stem cell transplantation (OR 8.73, 95% CI 1.05–72.54, p = 0.045) were associated with administration of cefiderocol as part of a combined regimen, whereas chronic kidney disease was associated with cefiderocol monotherapy (OR 0.38 for combined regimen, 95% CI 0.16–0.91, p = 0.029). Cumulative 30-day mortality was 19.8%, 45.0%, 20.7%, and 22.7% in patients receiving targeted cefiderocol for infections by Enterobacterales, A. baumannii, Pseudomonas aeruginosa, and any metallo-β-lactamase producers, respectively. Conclusions Cefiderocol is mainly used for targeted treatment, although empirical therapies account for more than 25% of prescriptions, thus requiring dedicated standardization and guidance. The almost equal distribution of cefiderocol monotherapy and cefiderocol-based combination therapies underlines the need for further study to ascertain possible differences in efficacy between the two approaches.