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The integration of advanced materials and photonic nanostructures can lead to enhanced biodetection capabilities, crucial in clinical scenarios and point-of-care diagnostics, where simplified strategies are essential. Herein, a molecularly imprinted polymer (MIP) photonic nanostructure is demonstrated, which selectively binding to transforming growth factor-beta (TGF-β), in which the sensing transduction is enhanced by bound states in the continuum (BICs). The MIP operating as a synthetic antibody matrix and coupled with BIC resonance, enhances the optical response to TGF-β at imprinted sites, leading to an augmented detection capability, thoroughly evaluated through spectral shift and optical lever analogue readout. The validation underscores the MIP-BIC sensor capability to detect TGF-β in spiked saliva, achieving a limit of detection of 10 fM and a resolution of 0.5 pM at physiological concentrations, with a precision of two orders of magnitude above discrimination threshold in patients. The MIP tailored selectivity is highlighted by an imprinting factor of 52, showcasing the sensor resistance to interference from other analytes. The MIP-BIC sensor architecture streamlines the detection process eliminating the need for complex sandwich immunoassays and demonstrates the potential for high-precision quantification. This positions the system as a robust tool for biomarker detection, especially in real-world diagnostic scenarios.

The Earth system has long lived with fires,1 , 2 but the impact of climate change on fire regimes has led to extreme wildfire events with higher intensity and faster spread.3 , 4 , 5 This has effects on ecosystems and resources, air pollution, and, ultimately, human societies.6 Facing these compounding challenges require interdisciplinary solutions and collaborations. In this Backstory, we bring together fire researchers across fields, aiming to foster discussions and collaborations across disciplines, for us to better understand how we can learn to live with fire.

We assembled the first gridded burned area (BA) database of national wildfire data (ONFIRE), a comprehensive and integrated resource for researchers, non-government organisations, and government agencies analysing wildfires in various regions of the Earth. We extracted and harmonised records from different regions and sources using open and reproducible methods, providing data in a common framework for the whole period available (starting from 1950 in Australia, 1959 in Canada, 1985 in Chile, 1980 in Europe, and 1984 in the United States) up to 2021 on a common 1° × 1° grid. The data originate from national agencies (often, ground mapping), thus representing the best local expert knowledge. Key opportunities and limits in using this dataset are discussed as well as possible future expansions of this open-source approach that should be explored. This dataset complements existing gridded BA data based on remote sensing and offers a valuable opportunity to better understand and assess fire regime changes, and their drivers, in these regions. The ONFIRE database can be freely accessed at https://zenodo.org/record/8289245 .

Mapping in situ eddy covariance measurements of terrestrial land–atmosphere fluxes to the globe is a key method for diagnosing the Earth system from a data-driven perspective. We describe the first global products (called X-BASE) from a newly implemented upscaling framework, FLUXCOM-X, representing an advancement from the previous generation of FLUXCOM products in terms of flexibility and technical capabilities. The X-BASE products are comprised of estimates of CO2 net ecosystem exchange (NEE), gross primary productivity (GPP), evapotranspiration (ET), and for the first time a novel, fully data-driven global transpiration product (ETT), at high spatial (0.05°) and temporal (hourly) resolution. X-BASE estimates the global NEE at −5.75 ± 0.33 Pg C yr−1 for the period 2001–2020, showing a much higher consistency with independent atmospheric carbon cycle constraints compared to the previous versions of FLUXCOM. The improvement of global NEE was likely only possible thanks to the international effort to increase the precision and consistency of eddy covariance collection and processing pipelines, as well as to the extension of the measurements to more site years resulting in a wider coverage of bioclimatic conditions. However, X-BASE global net ecosystem exchange shows a very low interannual variability, which is common to state-of-the-art data-driven flux products and remains a scientific challenge. With 125 ± 2.1 Pg C yr−1 for the same period, X-BASE GPP is slightly higher than previous FLUXCOM estimates, mostly in temperate and boreal areas. X-BASE evapotranspiration amounts to 74.7×103 ± 0.9×103 km3 globally for the years 2001–2020 but exceeds precipitation in many dry areas, likely indicating overestimation in these regions. On average 57 % of evapotranspiration is estimated to be transpiration, in good agreement with isotope-based approaches, but higher than estimates from many land surface models. Despite considerable improvements to the previous upscaling products, many further opportunities for development exist. Pathways of exploration include methodological choices in the selection and processing of eddy covariance and satellite observations, their ingestion into the framework, and the configuration of machine learning methods. For this, the new FLUXCOM-X framework was specifically designed to have the necessary flexibility to experiment, diagnose, and converge to more accurate global flux estimates.

Abstract Background Research and monitoring of human resources available for vision rehabilitation services has been a neglected area of work in the past. This study aims to offer an overview of the vision rehabilitation workforce available in Italy, in order to profile the distribution and number of human resources for vision rehabilitation. Methods Data on the available vision rehabilitation professionals were collected from the yearly report on the state of implementation of policies relating to the prevention of blindness, education and vision rehabilitation, according to a law which was passed by the Italian Ministry of Health, Department of Health Prevention. The report presents a review of all professional workers dealing with low vision rehabilitation centers in Italy between January 2005 and December 2019. Data on the distribution and type of services of government-supported low vision centers across the country were also obtained and examined. Results Of the 289 low vision rehabilitation workers in 2019, 28% were ophthalmologists, 31% orthoptists, 19% psychologists, 17% nurses and 5% social workers. The health workforce densities across the Italian regions ranged from 1.62 to 0.12 per 100.000. The density of vision rehabilitation workers showed a no growing trend from 2006 to 2015. During the study period, it was found a weak but statistically significant association of workforce density with the number of government-supported low vision centers across the Italian territory (r2 = 0.3, p

Abstract The tumor suppressor PTEN (phosphatase and tensin homolog deleted in chromosome 10) is genetically deleted or downregulated in many cancer types. Loss of PTEN protein expression is frequently found in lung cancer while genetic alterations are less abundant. PTEN expression is regulated at multiple genetic and epigenetic levels and even partial reduction of its expression increases cancer occurrence. We show that YAP and TAZ cooperate with EZH2, and MYC to transcriptionally repress onco-suppressor genes, including PTEN, in non-small cell lung cancer (NSCLC) cells. YAP/TAZ-EZH2-MYC transcriptional regulators form a nuclear complex that represses PTEN transcription, while their combinatorial targeting restores PTEN expression, attenuates NSCLC cell growth, and prevents compensatory responses induced by single treatments. Datasets analysis of NSCLC patients revealed that PTEN expression is negatively correlated to YAP/TAZ, EZH2 and MYC and that low expression of PTEN is predictive of poor prognosis, especially at earlier stages of the disease. These findings highlight the repressive role of the YAP/TAZ-EZH2-MYC axis on tumor-suppressor genes and offer a potential therapeutic strategy for lung cancer patients with low PTEN levels.

Abstract Defining the molecular mechanisms underlying cardiac resilience is crucial to find effective approaches to protect the heart. A physiologic level of ROS is produced in the heart by fatty acid oxidation, but stressful events can boost ROS and cause mitochondrial dysfunction and cardiac functional impairment. Melusin is a muscle specific chaperone required for myocardial compensatory remodeling during stress. Here we report that Melusin localizes in mitochondria where it binds the mitochondrial trifunctional protein, a key enzyme in fatty acid oxidation, and decreases it activity. Studying both mice and human induced pluripotent stem cell-derived cardiomyocytes, we found that Melusin reduces lipid oxidation in the myocardium and limits ROS generation in steady state and during pressure overload and doxorubicin treatment, preventing mitochondrial dysfunction. Accordingly, the treatment with the lipid oxidation inhibitor Trimetazidine concomitantly with stressful stimuli limits ROS accumulation and prevents long-term heart dysfunction. These findings disclose a physiologic mechanism of metabolic regulation in the heart and demonstrate that a timely restriction of lipid metabolism represents a potential therapeutic strategy to improve cardiac resilience to stress.

Abstract CoQ10 (Coenzyme Q10) is an essential fat-soluble metabolite that plays a key role in cellular metabolism. A less-known function of CoQ10 is whether it may act as a plasma membrane-stabilizing agent and whether this property can affect cancer development and progression. Here, we show that CoQ10 and its biosynthetic enzyme UBIAD1 play a critical role in plasmamembrane mechanical properties that are of interest for breast cancer (BC) progression and treatment. CoQ10 and UBIAD1 increase membrane fluidity leading to increased cell stiffness in BC. Furthermore, CoQ10 and UBIAD1 states impair ECM (extracellular matrix)-mediated oncogenic signaling and reduce ferroptosis resistance in BC settings. Analyses on human patients and mouse models reveal that UBIAD1 loss is associated with BC development and progression and UBIAD1 expression in BC limits CTCs (circulating tumor cells) survival and lung metastasis formation. Overall, this study reveals that CoQ10 and UBIAD1 can be further investigated to develop therapeutic interventions to treat BC patients with poor prognosis.

Roberto W Dal Negro,1 Paola Turco,1 Massimiliano Povero2 1National Centre for Respiratory Pharmacoeconomics and Pharmacoepidemiology - CESFAR, Verona, Italy; 2AdRes Health Economics and Outcomes Research, Turin, ItalyCorrespondence: Massimiliano Povero, Email m.povero@adreshe.comBackground: Chronic Obstructive Pulmonary Disease (COPD) is a respiratory condition characterized by heterogeneous abnormalities of the airways and lung parenchyma that cause different clinical presentations. The assessment of the prevailing pathogenetic components underlying COPD is not usually pursued in daily practice, also due to technological limitations and cost.Aim: To assess non-invasively the lung emphysema component of COPD by the simultaneous measurement of DLNO and DLCO via a single-breath (sDLNO and sDLCO).Methods: COPD patients aged ≥ 40 years of both genders were recruited consecutively and labelled by computed tomography as “with significant” emphysema (> 10% of CT lung volume) or “with negligible” emphysema otherwise. Current lung function tests such as sDLNO, sDLCO and Vc (the lung capillary blood volume) were measured. All possible subsets of independent spirometric and diffusive parameters were tested as predictors of emphysema, and their predicted power compared to each parameter alone by ROC analysis and area under the curve (AUC).Results: Thirty-one patients with “significant emphysema” were compared to thirty-one with “negligible emphysema”. FEV1 and FEV1/FVC seemed to be the best spirometric predictors (AUC 0.80 and 0.81, respectively), while sDLCO and Vc had the highest predicted power among diffusive parameters (AUC 0.92 and 0.94, respectively). sDLCO and Vc values were the parameters most correlated to the extent of CT emphysema. Six subsets of independent predictors were identified and included at least one spirometric and one diffusive parameter. According to goodness-to-fit scores (AIC, BIC, log-likelihood and pseudo R2), RV coupled with sDLCO or Vc proved the best predictors of emphysema.Conclusion: When investigating the parenchymal destructive component due to emphysema occurring in COPD, sDLNO, sDLCO and Vc do enhance the predictive power of current spirometric measures substantially. sDLNO, sDLCO and Vc contribute to phenotype of the main pathogenetic components of COPD easily and with high sensitivity. Organizational problems, radiation exposure, time and costs could be reduced, while personalized and precision medicine could be noticeably implemented.Keywords: COPD, parenchymal destruction, emphysema, lung capillary blood volume, simultaneous single-breath NO and CO diffusing capacity, precision medicine

Abstract Objective Women with type 2 diabetes experience higher cardiovascular and mortality risk than men possibly because of a sub-optimal cardio-protective treatment. We evaluated whether an intensive multifactorial therapy (MT) produces similar protective effect on development of adverse outcomes in women and men. Research design and methods Nephropathy in Diabetes type 2 study is an open-label cluster randomized trial comparing the effect of Usual Care (UC) or MT of main cardiovascular risk factors (blood pressure

Background and objective: Hypertension (HTN) has been linked to an elevated risk of prostate cancer (PC) development and poorer prognosis in localized cases, and is a common side effect of hormonal PC treatments. However, its relationship with the prognosis of metastatic PC is still unclear. We assessed the prognostic role of treatment-related HTN in patients with de novo metastatic hormone-sensitive PC (mHSPC) undergoing androgen deprivation therapy (ADT) alone or in combination with docetaxel or androgen receptor pathway inhibitors (ARPIs). Methods: Our retrospective analysis included 100 patients with de novo mHSPC treated with ADT, ADT + docetaxel, or ADT + ARPI between 2014 and 2021. Data on clinical variables, antihypertensive drugs, and blood pressure were collected from treatment initiation to 7 mo from ADT start. HTN development within 7 mo from hormonal treatment initiation was graded according to the Common Toxicity Criteria for Adverse Events version 5.0, and Cox analyses were performed for time to castration resistance (TTCR) and overall survival (OS). Key findings and limitations: In the overall population, grade (G) 2–3 HTN development within 7 mo from hormonal treatment initiation was associated with improved TTCR and OS at both univariate (TTCR: 19.8 vs 7.9 mo, hazard ratio [HR]: 0.35, 95% confidence interval [CI]: 0.20–0.63, p

Abstract The Bcl2-associated athanogene-3 (BAG3) protein, a critical regulator of cellular survival, has been identified as a potential therapeutic target in various malignancies. This study investigates the role of BAG3 within stromal fibroblasts and its interaction with B-cell chronic lymphocytic leukemia (B-CLL) cells. Previous research demonstrated that BAG3 maintains the active state of pancreatic stellate cells (PSCs) and aids pancreatic ductal adenocarcinoma (PDAC) spread via cytokine release. To explore BAG3’s role in bone marrow-derived stromal fibroblasts, BAG3 was silenced in HS-5 cells using siRNA. In co-culture experiments with PBMCs from B-CLL patients, BAG3 silencing in HS-5 cells increased apoptosis and decreased phosphorylation of BTK, AKT, and ERK in B-CLL cells, thus disrupting their pro-survival key signaling pathways. The observation of fibroblast-activated protein (FAP) positive cells in infiltrated bone marrow specimens co-expressing BAG3 further support the involvement of the protein in fibroblast-mediated tumor survival. Additionally, BAG3 appears to support B-CLL survival by modulating cytokine networks, including IL-10 and CXCL12, which are essential for leukemic cell survival and proliferation. A robust correlation between BAG3 expression and the levels of CXCL12 and IL-10 was observed in both co-cultures and patient specimens. These findings point out the need for a more in-depth comprehension of the intricate network of interactions within the tumor microenvironment and provide valuable insights for the selection of new potential therapeutic targets in the medical treatment of CLL.

A correct injection technique is essential in order to ensure the effectiveness of insulin and to achieve good metabolic control, and the use of suitable needles is fundamental. Today, technological evolution has transformed insulin needles into innovative tools able to guarantee an effective and safe administration of insulin, to reduce local complications, such as lipodystrophies that are an obstacle to the effectiveness of the treatment itself, and to minimize the pain of the injection, a crucial factor in the acceptance of therapy and for compliance. The steering committee of the scientific society SIMDO has commissioned the scientific committee and some members of the board to draw up an official SIMDO point of view/consensus on the use of insulin needles. In this way, a group that has combined the experience gained in their field of expertise—diabetologists operating in the public and private sectors, nurses, psychologists, and patients—was set up. The aim is to give indications regarding insulin injection techniques, combining themes such as technology innovation, education in self-management, and psychological support for the patient into a unified approach based on the priority area of patient quality of life. The document will provide operational recommendations that integrate the directions regarding the standards of care for diabetes resulting from the most recent scientific acquisitions with the concept of quality at 360°, as it emerged from the point of view of all the operators involved, but with the patient’s interests as a central focal point.

Abstract Background The application of semi-conductor detectors such as cadmium–zinc–telluride (CZT) in nuclear medicine improves extrinsic energy resolution and count sensitivity due to the direct conversion of gamma photons into electric signals. A 3D-ring pixelated CZT system named StarGuide was recently developed and implemented by GE HealthCare for SPECT acquisition. The system consists of 12 detector columns with seven modules of 16 × 16 CZT pixelated crystals, each with an integrated parallel-hole tungsten collimator. The axial coverage is 27.5 cm. The detector thickness is 7.25 mm, which allows acquisitions in the energy range [40–279] keV. Since there is currently no performance characterization specific to 3D-ring CZT SPECT systems, the National Electrical Manufacturers Association (NEMA) NU 1-2018 clinical standard can be tailored to these cameras. The aim of this study was to evaluate the performance of the SPECT/CT StarGuide system according to the NEMA NU 1-2018 clinical standard specifically adapted to characterize the new 3D-ring CZT. Results Due to the integrated collimator, the system geometry and the pixelated nature of the detector, some NEMA tests have been adapted to the features of the system. The extrinsic measured energy resolution was about 5–6% for the tested isotopes (99mTc, 123I and 57Co); the maximum count rate was 760 kcps and the observed count rate at 20% loss was 917 kcps. The system spatial resolution in air extrapolated at 10 cm with 99mTc was 7.2 mm, while the SPECT spatial resolutions with scatter were 4.2, 3.7 and 3.6 mm in a central, radial and tangential direction respectively. Single head sensitivity value for 99mTc was 97 cps/MBq; with 12 detector columns, the system volumetric sensitivity reached 520 kcps MBq−1 cc−1. Conclusions The performance tests of the StarGuide can be performed according to the NEMA NU 1-2018 standard with some adaptations. The system has shown promising results, particularly in terms of energy resolution, spatial resolution and volumetric sensitivity, potentially leading to higher quality clinical images.

Abstract Glioblastoma is the most common and aggressive primary malignant brain tumor with poor prognosis. Novel immunotherapeutic approaches are currently under investigation. Even though magnetic resonance imaging (MRI) is the most important imaging tool for treatment monitoring, response assessment is often hampered by therapy-related tissue changes. As tumor and therapy-associated tissue reactions differ structurally, we hypothesize that biomechanics could be a pertinent imaging proxy for differentiation. Longitudinal MRI and magnetic resonance elastography (MRE) were performed to monitor response to immunotherapy with a toll-like receptor 7/8 agonist in orthotopic syngeneic experimental glioma. Imaging results were correlated to histology and light sheet microscopy data. Here, we identify MRE as a promising non-invasive imaging method for immunotherapy-monitoring by quantifying changes in response-related tumor mechanics. Specifically, we show that a relative softening of treated compared to untreated tumors is linked to the inflammatory processes following therapy-induced re-education of tumor-associated myeloid cells. Mechanistically, combined effects of myeloid influx and inflammation including extracellular matrix degradation following immunotherapy form the basis of treated tumors being softer than untreated glioma. This is a very early indicator of therapy response outperforming established imaging metrics such as tumor volume. The overall anti-tumor inflammatory processes likely have similar effects on human brain tissue biomechanics, making MRE a promising tool for gauging response to immunotherapy in glioma patients early, thereby strongly impacting patient pathway.

Abstract Objective This paper presents a comprehensive analysis of perioperative patient deterioration by developing predictive models that evaluate unanticipated ICU admissions and in-hospital mortality both as distinct and combined outcomes. Materials and Methods With less than 1% of cases resulting in at least one of these outcomes, we investigated 98 features to identify their role in predicting patient deterioration, using univariate analyses. Additionally, multivariate analyses were performed by employing logistic regression (LR) with LASSO regularization. We also assessed classification models, including non-linear classifiers like Support Vector Machines, Random Forest, and XGBoost. Results During evaluation, careful attention was paid to the data imbalance therefore multiple evaluation metrics were used, which are less sensitive to imbalance. These metrics included the area under the receiver operating characteristics, precision-recall and kappa curves, and the precision, sensitivity, kappa, and F1-score. Combining unanticipated ICU admissions and mortality into a single outcome improved predictive performance overall. However, this led to reduced accuracy in predicting individual forms of deterioration, with LR showing the best performance for the combined prediction. Discussion The study underscores the significance of specific perioperative features in predicting patient deterioration, especially revealed by univariate analysis. Importantly, interpretable models like logistic regression outperformed complex classifiers, suggesting their practicality. Especially, when combined in an ensemble model for predicting multiple forms of deterioration. These findings were mostly limited by the large imbalance in data as post-operative deterioration is a rare occurrence. Future research should therefore focus on capturing more deterioration events and possibly extending validation to multi-center studies. Conclusions This work demonstrates the potential for accurate prediction of perioperative patient deterioration, highlighting the importance of several perioperative features and the practicality of interpretable models like logistic regression, and ensemble models for the prediction of several outcome types. In future clinical practice these data-driven prediction models might form the basis for post-operative risk stratification by providing an evidence-based assessment of risk.

Abstract Early metastatic disease development is one characteristic that defines triple-negative breast cancer (TNBC) as the most aggressive breast cancer (BC) subtype. Numerous studies have identified long non-coding RNAs (lncRNA) as critical players in regulating tumor progression and metastasis formation. Here, we show that MALAT1, a long non-coding RNA known to promote various features of BC malignancy, such as migration and neo angiogenesis, regulates TNBC cell response to hypoxia. By profiling MALAT1-associated transcripts, we discovered that lncRNA MALAT1 interacts with the mRNA encoding WTAP protein, previously reported as a component of the N6-methyladenosine (m6A) modification writer complex. In hypoxic conditions, MALAT1 positively regulates WTAP protein expression, which influences the response to hypoxia by favoring the transcription of the master regulators HIF1α and HIF1β. Furthermore, WTAP stimulates BC cell migratory ability and the expression of N-Cadherin and Vimentin, hallmarks of epithelial-to-mesenchymal transition (EMT). In conclusion, this study highlights the functional axis comprising MALAT1 and WTAP as a novel prognostic marker of TNBC progression and as a potential target for the development of therapeutic approaches for TNBC treatment.

Record-breaking summer forest fires have become a regular occurrence in California. Observations indicate a fivefold increase in summer burned area (BA) in forests in northern and central California during 1996 to 2021 relative to 1971 to 1995. While the higher temperature and increased dryness have been suggested to be the leading causes of increased BA, the extent to which BA changes are due to natural variability or anthropogenic climate change remains unresolved. Here, we develop a climate-driven model of summer BA evolution in California and combine it with natural-only and historical climate simulations to assess the importance of anthropogenic climate change on increased BA. Our results indicate that nearly all the observed increase in BA is due to anthropogenic climate change as historical model simulations accounting for anthropogenic forcing yield 172% (range 84 to 310%) more area burned than simulations with natural forcing only. We detect the signal of combined historical forcing on the observed BA emerging in 2001 with no detectable influence of the natural forcing alone. In addition, even when considering fuel limitations from fire-fuel feedbacks, a 3 to 52% increase in BA relative to the last decades is expected in the next decades (2031 to 2050), highlighting the need for proactive adaptations.

Oncotherapy can shape intestinal microbiota, which, in turn, may influence therapy effectiveness. Furthermore, microbiome signatures during treatments can be leveraged for the development of personalised therapeutic protocols in cancer treatment based on the identification of microbiota profiles as prognostic tools. Here, for the first time, the trajectory of gut and salivary microbiota in a patient treated with Larotrectinib, a targeted therapy approved for diagnosed glioblastoma multiforme neurotrophic tyrosine receptor kinase (NTRK) gene fusion-positive, has been accurately investigated. We based our analyses on histological diagnosis, genomic and epigenomic profiling of tumour DNA, and faecal and salivary full-length 16S rRNA gene sequencing. The study clearly evidenced a remodelling of the bacterial communities following 1 month of the NTRK-inhibitor treatment, at both gut and oral levels. We reported a boosting of specific bacteria also described in response to other chemotherapeutic approaches, such as Enterococcus faecium, E. hirae, Akkermansia muciniphila, Barnesiella intestinihominis, and Bacteroides fragilis. Moreover, several bacterial species were similarly modulated upon Larotrectinib in faecal and saliva samples. Our results suggest a parallel dynamism of microbiota profiles in both body matrices possibly useful to identify microbial biomarkers as contributors to precision medicine in cancer therapies.

Abstract The integration of advanced materials and photonic nanostructures can lead to enhanced biodetection capabilities, crucial in clinical scenarios and point‐of‐care diagnostics, where simplified strategies are essential. Herein, a molecularly imprinted polymer (MIP) photonic nanostructure is demonstrated, which selectively binding to transforming growth factor‐beta (TGF‐β), in which the sensing transduction is enhanced by bound states in the continuum (BICs). The MIP operating as a synthetic antibody matrix and coupled with BIC resonance, enhances the optical response to TGF‐β at imprinted sites, leading to an augmented detection capability, thoroughly evaluated through spectral shift and optical lever analogue readout. The validation underscores the MIP‐BIC sensor capability to detect TGF‐β in spiked saliva, achieving a limit of detection of 10 fM and a resolution of 0.5 pM at physiological concentrations, with a precision of two orders of magnitude above discrimination threshold in patients. The MIP tailored selectivity is highlighted by an imprinting factor of 52, showcasing the sensor resistance to interference from other analytes. The MIP‐BIC sensor architecture streamlines the detection process eliminating the need for complex sandwich immunoassays and demonstrates the potential for high‐precision quantification. This positions the system as a robust tool for biomarker detection, especially in real‐world diagnostic scenarios.

Pediatric Autoimmune Neuropsychiatric Disorder Associated with Streptococcal Infections (PANDAS) and Pediatric Acute-onset Neuropsychiatric Syndrome (PANS) are broad diagnoses that encompass a range of sudden-onset neuropsychiatric symptoms in children, which can include obsessive-compulsive disorder (OCD), tics, anxiety, emotional instability, and cognitive difficulties. Unlike PANDAS, PANS is not strictly linked to group A streptococcal infections but can be triggered by various infectious or environmental factors. Lights and shadows remain upon the management of children with PANS and PANDAS and there is no clear consensus regarding definition, diagnostic criteria, treatment, and follow-up. The aim of the present study was to evaluate the level of agreement on PANS and PANDAS definition, diagnostic criteria, treatment and follow-up and to assess on the basis of recent studies whether there is a need to modify the current recommendations used by primary care pediatricians and hospital pediatricians in clinical practice in order to improve outcomes. Using the Delphi method, this consensus provides shared indications on PANS and PANDAS management in pediatric age, based on the most updated literature. This work represents, in our opinion, the most complete and up-to-date information on the diagnosis of PANS and PANDAS, as well as consensus statements about several aspects of clinical care. Undoubtedly, more randomized and controlled trials are needed in the pediatric population to better define the best management, also in terms of adequate follow-up examinations and period of observation.

Background and Aims: We aimed to characterize the epidemiologic and comorbidities profiles of patients with chronic Hepatitis D (CHD) followed in clinical practice in Italy and explored their interferon (IFN) eligibility. Methods: This was a cross-sectional study of the PITER cohort consisting of consecutive HBsAg-positive patients from 59 centers over the period 2019-2023. Multivariable analysis was performed by logistic regression model. Results: Of 5492 HBsAg-positive enrolled patients, 4152 (75.6%) were screened for HDV, 422 (10.2%) were anti-HDV positive. Compared with HBsAg mono-infected, anti-HDV positive patients were more often younger, non-Italians, with a history of drug use, had elevated alanine transaminase (ALT), cirrhosis, or hepatocellular carcinoma (HCC). Compared with Italians, anti-HDV positive non-Italians were younger (42.2% age ≤ 40 years vs. 2.1%; P < 0.001), more often females (males 43.0% vs. 68.6%; P < 0.001) with less frequent cirrhosis and HCC. HDV-RNA was detected in 63.2% of anti-HDV-positive patients, who were more likely to have elevated ALT, cirrhosis, and HCC. Extrahepatic comorbidities were present in 47.4% of anti-HDV positive patients and could affect the eligibility of IFN-containing therapies in at least 53.0% of patients in care. Conclusions: CHD affects young, foreign-born patients and older Italians, of whom two-thirds had cirrhosis or HCC. Comorbidities were frequent in both Italians and non-Italians and impacted eligibility for IFN.