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Models are a core element in performing local estimation of the climate change input. In this work, a novel approach to perform a fast downscaling of global temperature anomalies on a regional level is presented. The approach is based on a set of data-driven models linking global temperature anomalies and regional and global emissions to regional temperature anomalies. In particular, due to the limited number of available data, a linear autoregressive structure with exogenous input (ARX) has been considered. To demonstrate their relevance to the existing literature and context, the proposed ARX models have been employed to evaluate the impact of temperature anomalies on rice production in a socially, economically, and climatologically fragile area like Southeast Asia. The results show a significant impact on this region, with estimations strongly in accordance with information presented in the literature from different sources and scientific fields. The work represents a first step towards the development of a fast, data-driven, holistic approach to the climate change impact evaluation problem. The proposed ARX data-driven models reveal a novel and feasible way to downscale global temperature anomalies to regional levels, showing their importance in comprehending global temperature anomalies, emissions, and regional climatic conditions.

This study introduces and evaluates a methodology to define optimal integrated short and long-term air pollution control measures, to support policy formulation by Local Authorities. The approach utilized in this methodology is based on a receding horizon strategy. In this approach, an autoregressive model provides the dynamic characteristics of air quality within a designated time period. The model is established using daily observed data on pollutant concentration, meteorological variables, and estimated emission data in the study area. The model is the core of a model predictive control based on the solution, at each time step, of the resulting optimization problem. The effectiveness of the overall control has been assessed in the context of controlling NO2 concentrations within the city of Milan. The outcomes of the study demonstrate that this control system can serve as a valuable tool to assist Local Authorities in making informed decisions regarding appropriate air quality management strategies.

In breast cancer volumetric-modulated arc therapy (VMAT) planning, the rotation of the gantry around the target implies a greater dose spreading to the whole heart, compared to tangential-field standard treatment. A consecutive cohort of 121 breast cancer patients treated with the VMAT technique was investigated. The correlation of breast volume, heart volume and lung volume with mean heart dose (mHD) and mean and maximum LAD dose (mLAD dose, MLAD dose) was tested, and a subsequent a linear regression analysis was carried out. VMAT treatment plans from 56 left breast cancer and 65 right breast cancer patients were analyzed. For right-sided patients, breast volume was significantly correlated with mHD, mLAD and MLAD dose, while for left-sided patients, breast volume was significantly correlated with mHD and mLAD, while heart volume and lung volume were correlated with mHD, mLAD and MLAD dose. Breast volume was the only predictor of increased heart and LAD dose (p ≤ 0.001) for right-sided patients. In left-sided patients, heart and lung were also predictors of increased mHD (p = 0.005, p ≤ 0.001) and mean LAD dose (p = 0.009, p ≤ 0.001). In this study, we observed an increase in heart and LAD doses in larger-breasted patients treated with VMAT planning. In right-sided patients, breast volume was shown to be the only predictor of increased heart dose and LAD dose.

Background: The extent of the SARS-CoV-2 short-term evolution under Remdesivir (RDV) exposure and whether it varies across different upper respiratory compartments are not fully understood. Methods: Patients hospitalized for COVID-19, with or without RDV therapy, were enrolled and completed up to three visits, in which they provided specimens from four respiratory compartments. Near full-length genome SARS-CoV-2 sequences were obtained from viral RNA, standard lineage and variant assignments were performed, and viral mutations in the RNA-dependent RNA polymerase (RdRp) region—the RDV target gene—were detected and compared between participants with and without RDV, across the four compartments, within participants across visits, and versus a larger sequence dataset. The statistical analysis used a generalized linear mixed-effects model. Results: A total of 139 sequences were obtained from 37 out of the 44 (84%) enrolled participants. The genotyping success varied across respiratory compartments, which ranged from 42% with oropharyngeal specimens to 67% with nasopharyngeal specimens and showed improvement with higher viral loads. No RdRp mutations known to be associated with RDV resistance were identified, and for 34 detected mutations at 32 amino acid positions that are not known as RDV-associated, there was no evidence of any associations with the RDV exposure, respiratory compartment, or time. At least 1 of these 34 mutations were detected in all participants, and some differed from the larger sequence dataset. Conclusions: This study highlighted the SARS-CoV-2 short-term genomic stability within hosts and across upper respiratory compartments, which suggests a lack of evolution of RDV resistance over time. This contributes to our understanding of SARS-CoV-2 genomic dynamics.

Background. Oxidative stress and inflammation are typically implied in atherosclerosis pathogenesis and progression, especially in coronary artery disease (CAD). Our objective was to investigate the oxidative stress and inflammation burden directly associated with atherosclerotic plaque in patients with stable coronary disease undergoing coronary artery bypass graft (CABG) surgery. Specifically, markers of oxidative stress and inflammation were compared in blood samples obtained from the atherosclerotic left anterior descending artery (LAD) and blood samples obtained from the healthy left internal thoracic artery (LITA), used as a bypass graft, within the same patient. Methods. Twenty patients scheduled for off-pump CABG were enrolled. Blood samples were collected from the LITA below anastomosis and the LAD below the stenosis. Samples were analysed for oxidative stress (sNOXdp, H2O2, NO) and inflammation markers (TNFα, IL-6, IL-1β, IL-10). Results. The analysis showed a significant increase in oxidative stress burden in the LAD as compared to LITA, as indicated by higher sNOX2-dp and H2O2 levels and lower NO levels (p < 0.01). Also, pro-inflammatory cytokines were increased in the LAD as compared to the LITA, as indicated by higher TNFα and IL-6 amounts (p < 0.01). On the other hand, no significant differences could be seen regarding IL-1β and IL-10 levels between the two groups. Conclusions. The oxidative stress and inflammatory burden are specifically enhanced in the LAD artery of stable coronary patients compared to systemic blood from the LITA of stable coronary patients.

Conventional radiography is widely used for postmortem foetal imaging, but its role in diagnosing congenital anomalies is debated. This study aimed to assess the effectiveness of X-rays in detecting skeletal abnormalities and guiding genetic analysis and counselling. This is a retrospective analysis of all post-abortion diagnostic imaging studies conducted at a centre serving a population of over 300,000 inhabitants from 2008 to 2023. The data were analysed using descriptive statistics. X-rays of 81 aborted foetuses (total of 308 projections; mean: 3.8 projections/examination; SD: 1.79) were included. We detected 137 skeletal anomalies. In seven cases (12.7%), skeletal anomalies identified through radiology were missed by prenatal sonography. The autopsy confirmed radiological data in all cases except for two radiological false positives. Additionally, radiology failed to identify a case of syndactyly, which was revealed by anatomopathology. X-ray is crucial for accurately classifying skeletal abnormalities, determining the causes of spontaneous abortion, and guiding the request for genetic counselling. Formal training for both technicians and radiologists, as well as multidisciplinary teamwork, is necessary to perform X-ray examinations on aborted foetuses and interpret the results effectively.

Atherosclerosis is a pathological condition characterized by the inflammation of arterial vessels, leading to serious cardiovascular outcomes such as myocardial infarction, stroke, and death [...]

A new fossil gray whale genus and species, Glaucobalaena inopinata, is established based on craniomandibular remains from the Pliocene Sabbie d’Asti Formation, Piedmont, northwestern Italy. The holotype (MGPT-PU 19512) consists of two cranial fragments corresponding to the posterolateral corners of the skull, including both partial periotics, and in the posterior portion of the right mandibular ramus preserving the condyle and angular process. The new taxon is characterized by gray whale (eschrichtiid) synapomorphies in the posterior portion of the mandible (dorsally raised mandibular condyle with articular surface faced dorsoposteriorly, well-developed and robust angular process of the mandible) and in the earbone (massive transverse elongation of the pars cochlearis, indistinct flange of the ventrolateral tuberosity, and triangular and short anterior process of the periotic). A CT scan of the cranial fragments allowed us to reconstruct tridimensional renderings of the periotic, revealing the dorsal morphology of this bone. A phylogenetic analysis confirmed the inclusion of Glaucobalaena inopinata within Eschrichtiidae (the family to whom gray whales are included) and showed that it is monophyletic with Gricetoides aurorae; our phylogenetic results show that Eschrichtioides gastaldii is the sister group of the genus Eschrichtius. Our work lends further support to the idea that Eschrichtiidae is a separate family of baleen whales, characterized by specialized ecomorphological characters evident in both skull and mandibular architecture.

Glaucoma is chronic optic neuropathy whose pathogenesis has been associated with the altered metabolism of Trabecular Meshwork Cells, which is a cell type involved in the synthesis and remodeling of the trabecular meshwork, the main drainage pathway of the aqueous humor. Starting from previous findings supporting altered ubiquitin signaling, in this study, we investigated the ubiquitin-mediated turnover of myocilin (MYOC/TIGR gene), which is a glycoprotein with a recognized role in glaucoma pathogenesis, in a human Trabecular Meshwork strain cultivated in vitro in the presence of dexamethasone. This is a validated experimental model of steroid-induced glaucoma, and myocilin upregulation by glucocorticoids is a phenotypic marker of Trabecular Meshwork strains. Western blotting and native-gel electrophoresis first uncovered that, in the presence of dexamethasone, myocilin turnover by proteasome particles was slower than in the absence of the drug. Thereafter, co-immunoprecipitation, RT-PCR and gene-silencing studies identified STUB1/CHIP as a candidate E3-ligase of myocilin. In this regard, dexamethasone treatment was found to downregulate STUB1/CHIP levels by likely promoting its proteasome-mediated turnover. Hence, to strengthen the working hypothesis about global alterations of ubiquitin-signaling, the first profiling of TMCs ubiquitylome, in the presence and absence of dexamethasone, was here undertaken by diGLY proteomics. Application of this workflow effectively highlighted a robust dysregulation of key pathways (e.g., phospholipid signaling, β-catenin, cell cycle regulation) in dexamethasone-treated Trabecular Meshwork Cells, providing an ubiquitin-centered perspective around the effect of glucocorticoids on metabolism and glaucoma pathogenesis.

On 4 November 2021, during the rising phase of solar cycle 25, an intense geomagnetic storm (Kp = 8−) occurred. The effects of this storm on the outer magnetospheric region up to the ionospheric heights have already been examined in previous investigations. This work is focused on the analysis of the solar wind conditions before and during the geomagnetic storm, the high-latitude electrodynamics conditions, estimated through empirical models, and the response of the atmosphere in both hemispheres, based on parameters from the ECMWF ERA5 atmospheric reanalysis dataset. Our investigations are also supported by counter-test analysis and Monte Carlo tests. We find, for both hemispheres, a significant correspondence, within 1–2 days, between high-latitude electrodynamics variations and changes in the temperature, specific humidity, and meridional and zonal winds, in both the troposphere and stratosphere. The results indicate that, in the complex solar wind–atmosphere relationship, a significant role might be played by the intensification of the polar cap potential. We also study the reciprocal relation between the ionospheric Joule heating, calculated from a model, and two adiabatic invariants used in the analysis of solar wind turbulence.

T cell exhaustion limits antitumor immunity, but the molecular determinants of this process remain poorly understood. Using a chronic stimulation assay, we performed genome-wide CRISPR-Cas9 screens to systematically discover regulators of T cell exhaustion, which identified an enrichment of epigenetic factors. In vivo CRISPR screens in murine and human tumor models demonstrated that perturbation of the INO80 and BAF chromatin remodeling complexes improved T cell persistence in tumors. In vivo Perturb-seq revealed distinct transcriptional roles of each complex and that depletion of canonical BAF complex members, including Arid1a, resulted in the maintenance of an effector program and downregulation of exhaustion-related genes in tumor-infiltrating T cells. Finally, Arid1a depletion limited the acquisition of exhaustion-associated chromatin accessibility and led to improved antitumor immunity. In summary, we provide an atlas of the genetic regulators of T cell exhaustion and demonstrate that modulation of epigenetic state can improve T cell responses in cancer immunotherapy.

Housing has been identified as one of the most important areas related to individual well-being in emerging adults attending a tertiary educational institution. Thus, the purpose of this systematic review is to explore the relationship between students' housing conditions and students' psychical, mental, and emotional wellbeing. The review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Outcomes were categorised into 10 categories: (1) homesickness and adaptation to college life; (2) overall health and distress; (3) sleep; (4) depression, anxiety, and other mental health conditions; (5) alcohol abuse; (6) substance abuse; (7) tobacco use; (8) internet addiction; (9) eating disorders; and (10) sexual behaviours. Student housing conditions play an important role in a variety of health and health-related problems. These findings underscore the relationship between housing conditions and different facets of students' mental and physical wellbeing, emphasising the importance of addressing housing conditions in mental health prevention and intervention programmes.