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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 .

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

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.