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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.