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Francesco Facchinetti, Paola Bordi, Alessandro Leonetti, Sebastiano Buti, Marcello Tiseo Medical Oncology Unit, University Hospital of Parma, Parma, Italy Abstract: Programed cell death-1/programed death ligand-1 (PD-1/PD-L1) blockade represents an affirmed reality in the treatment of advanced non-small-cell lung cancer (NSCLC) patients. Atezolizumab, an anti-PD-L1 agent, figures among the drugs that provide previously unenvisaged outcomes in the pretreated setting of metastatic NSCLC. Increasing evidence vouches for the early administration of PD-1/PD-L1 blockers in untreated patients, encompassing atezolizumab combinations with chemotherapy and the anti-angiogenic agent bevacizumab. Moreover, the development of atezolizumab allowed to derive several hints regarding clinical and immunological factors predictive of its activity and efficacy, some of them exclusive among this class of drugs. This review provides an overview of atezolizumab development throughout clinical trials toward its applicability in the routine practice, with a particular focus on patient selection based on clinical and immune-related factors. Keywords: non-small cell lung cancer, NSCLC, immune checkpoint blockers, ICB, PD-1, PD-L1, atezolizumab development, biomarkers

The 2022 global mpox outbreak was driven by human-to-human transmission, but modes of transmission by sexual relationship versus sexual contact remain unclear. We evaluated sexual transmission of mpox by using monkeypox virus (MPXV) G2R-mRNA as a marker of ongoing viral replication through in vitro experiments. We analyzed clinical samples of 15 MPXV-positive patients in Italy from different biological regions by using the setup method. The presence of MPXV DNA, MPXV G2R-mRNA, or both in all analyzed lesion swab samples, independent of viral load, confirmed a higher infectivity risk from skin lesions. Positivity for MPXV G2R-mRNA in nasopharyngeal swabs was associated with high MPXV load, whereas positive results for MPXV G2R-mRNA were obtained only in the 2 semen samples with the lowest MPXV loads. Our results suggest that close or skin-to-skin contact during sexual intercourse is the main route of sexual transmission and that semen is a minor driver of infection, regardless of MPXV load.

Background: Almost 10% of women in reproductive age are diagnosed with ovarian endometriomas and can experience symptoms and infertility disorders. Ovarian endometriomas can be treated with medical or surgical therapy. Objective: To assess whether long-term therapy with dienogest or oral cyclic estrogen-progestogens is effective in reducing the size of ovarian endometriomas, alleviating associated symptoms, and reducing the requirement for surgery. Design: Prospective non-interventional cohort study. Methods: We enrolled childbearing women diagnosed with ovarian endometriomas. We collected demographic, clinical, and surgical data, including the evaluation of ovarian endometrioma-associated symptoms and pain using the visual analog scale. We grouped the women according to treatment regimen into dienogest, estrogen-progestogens, and no-treatment. Patient’s assessment was performed at baseline and after 12 months evaluating the largest ovarian endometrioma diameter (in millimeters) and the associated symptoms. Furthermore, we analyzed the impact of hormonal treatment in a sub-group of women fulfilling at baseline the criteria for a first-line surgical approach (ovarian endometrioma > 30 mm with visual analog scale > 8 or ovarian endometrioma > 40 mm before assisted reproductive treatments or any ovarian endometrioma(s) > 60 mm). Results: We enrolled 142 patients: 62, 38, and 42 in dienogest, estrogen-progestogens, and no-treatment groups, respectively. No significant differences were found regarding baseline characteristics. After 12 months, the mean largest ovarian endometrioma diameter increased in the no-treatment group (31.1 versus 33.8; p

Extended Abstract Introduction and Objective: The side ditch, which is built for the purpose of draining the surface currents and protecting the road construction, is eroded under the influence of the runoff speed during heavy rains and the sediments are transferred to the rivers and water ecosystems. Determining the impact thresholds of rainfall in different protection treatments on the sedimentation process of the side ditch can be a suitable tool for managing and planning the side ditch protection of forest roads throughout the year. The use of environmentally friendly techniques for the protection of roadsides has a direct effect on the quality and durability of road construction and ensuring traffic safety. Material and Methods: In this research, while monitoring the intensity and duration of rainfall of Dr. Bahramnia's forestry project in Golestan province and collecting data throughout the year, in relation to measuring the amount of sediment delivered after each rainfall through trapping at the beginning And the end of 30 plots of 150 meters in the first year before applying the treatments. The trapping involved digging a cylindrical pit with a diameter of 0.4 meters and a depth of 0.6 meters. Inside each trap, a calibrated indicator was installed to repeat the measurements, and during each visit, the sediment height and deposition level were measured to calculate the sediment volume and then multiplied by the apparent specific gravity of the sediment. In the second year, after identifying the streams that had the highest amount of sedimentation, the treatments of rocking with mountain material, rocking with river material, stair-stepping of the stream and pounding of the bed were carried out and the measurement of sediment after each rainfall, the same as the previous year was repeated. Results: Pearson correlation analysis showed that amount of sediment yield significantly increased by increasing rainfall duration. But, there wasn’t significant correlation between sediment yield and rainfall intensity. The amount of sediment yield decreased with preparing ditch conservation treatments. The sediment production was begun at 12 hours rainfall with intensity of 6.09 mm hr-1. Sediment production from the treatments of rocking with mountain material, rocking with river material, stair-stepping of the stream and pounding of the bed were 16000, 36000, 12150 and 27000 g yr-1. Conclusion: With comparisons of conservation treatments it was concluded that riprap with mountainous materials had best performance by sediment reduction of 84%. Nevertheless, it is suggested to carry out more and more comprehensive researches under different conditions of climate, slope and bedrock so that generalizable and practical results can be provided to control the sedimentation of the side streams.

Patients with acute myeloid leukemia (AML) carrying high-risk genetic lesions or high residual disease levels after therapy are particularly exposed to the risk of relapse. Here, we identified the long non-coding RNA CDK6-AS1 able to cluster an AML subgroup with peculiar gene signatures linked to hematopoietic cell differentiation and mitochondrial dynamics. CDK6-AS1 silencing triggered hematopoietic commitment in healthy CD34+ cells, whereas in AML cells the pathological undifferentiated state was rescued. This latter phenomenon derived from RUNX1 transcriptional control, responsible for the stemness of hematopoietic precursors and for the block of differentiation in AML. By CDK6-AS1 silencing in vitro, AML mitochondrial mass decreased with augmented pharmacological sensitivity to mitochondria-targeting drugs. In vivo, the combination of tigecycline and cytarabine reduced leukemia progression in the AML-PDX model with high CDK6-AS1 levels, supporting the concept of a mitochondrial vulnerability. Together, these findings uncover CDK6-AS1 as crucial in myeloid differentiation and mitochondrial mass regulation.

Objective. We aimed to report the real-world use and outcomes over time in immunocompromised individuals receiving tixagevimab/cilgavimab (T/C) pre-exposure prophylaxis (PrEP). Methods. This observational study included participants who received T/C PrEP, categorized into three groups: (i) No COVID-19 (NoC), i.e., participants who never had COVID-19; (ii) Hybrids (H), i.e., participants who had COVID-19 before PrEP; and (iii) Break-through Infections (BTIs), i.e., participants who had COVID-19 after PrEP. The study measured several immune markers at the administration of T/C (T0) at 3 (T1), 6 (T2), and 9 (T3) months afterward. These markers included: anti-receptor-binding domain (RBD) IgG antibodies; BA.5-neutralizing antibodies (nAbs); mucosal IgG; and T cell immunity. The incidence rate ratios for BTIs were analyzed using a Poisson regression model. Results. A total of 231 participants with a median age of 63 years (IQR 54.0–73.0). were included. Among these, 84% had hematological diseases and received a median of three vaccine doses. N = 72 participants belonged to the NoC group, N = 103 to the H group, and n = 56 to the BTI group (24%), with most BTIs being mild/moderate. The incidence rate (IR) of BTIs was 4.2 per 100 patient-months (95% CI 3.2–5.4), with no associated risk factors identified. There was a significant increase in anti-RBD IgG levels 3 months after the T/C administration in all groups, followed by a decline at 6 months, whereas at the same time points, geometric mean titers (GMTs) of anti-BA.5 nAbs were low for all groups and were around or below the detection threshold. No significant changes were observed in IFN-γ levels. The mucosal immune response was observed only 3 months after the PrEP administration. Conclusion. We provided a real-world experience model on the clinical efficacy of T/C PrEP in preventing severe COVID-19 during the Omicron wave through a comprehensive virological and immunological study. While waiting for the arrival of new monoclonal antibodies that can effectively neutralize the most recent variants, T/C PrEP remains the only viable strategy in the available armamentarium today to prevent COVID-19 complications in an extremely fragile population with suboptimal immune responses to COVID-19 vaccines.

Despite emerging evidence indicating that molecular SARS-CoV-2 tests performed on saliva have diagnostic sensitivity and specificity comparable to those observed with nasopharyngeal swabs (NPSs), most in vivo follow-up studies on the efficacy of drugs against SARS-CoV-2 have been performed on NPSs, not considering saliva as a possible alternative matrix. For this reason, in this study, we used, in parallel, saliva and NPS samples for the detection of SARS-CoV-2 by real-time RT-PCR in patients receiving Tixagevimab/Cilgavimab, Nirmatrelvir/Ritonavir, or Sotrovimab as a treatment against SARS-CoV-2. Our results showed a good correlation between the NPS and saliva samples for each drug; moreover, comparable changes in the cycle threshold (Ct) levels in saliva and NPSs were observed both 7 days and 30 days after treatment, thus confirming that the saliva represents a good matrix for in vivo follow-up studies verifying the effectiveness of treatments against SARS-CoV-2.

(1) Background: This paper illustrates an innovative methodological approach chosen to study and map the colors of the medieval wall painting of Santa Maria Antiqua in the Roman Forum, one of the pilot sites of the EHEM project (Enhancement of Heritage Experiences: The Middle Ages). Digital Layered Models of Architecture and Mural Paintings over Time). (2) Methods: Two methods were employed to gather information about colors and mapping. Specifically, colorimetry was utilized for spot measurements, and hypercolorimetric multispectral imaging (HMI) was employed to map the same colors sampled through colorimetry. (3) Results: Chromatic data for all colors in the wall paintings were obtained in the CIELAB color space. Additionally, chromatic similarity maps were generated using the innovative HMI system, a multispectral imaging technique capable of obtaining color data information through advanced calibration software named SpectraPick® (Version 1.1). This comprehensive approach facilitates a thorough understanding of color characteristics and distribution. (4) Conclusions: The color measurements and mapping represent significant advancements in the interpretation of medieval wall paintings, which are often fragmentary and stratigraphically complex. This research sheds new light on the colors used and enhances our understanding of the original appearance of the iconographic patterns. Furthermore, it enables the reconstruction of colors that closely resemble the originals.

Este artículo de reflexión explora el concepto de sustentabilidad turística para resignificar las formas de ejercer el tiempo libre y de explorar herramientas para el desarrollo rural. Se llevó a cabo un estudio de caso simple, con enfoque descolonial, con la intención de abordar un referente empírico sobre nuevos paradigmas del turismo, que se inscriben en la lógica del tiempo libre de calidad, la comunalidad y la economía social y solidaria. Se concluye que la perspectiva descolonial en el turismo es una manera de pensar el tiempo libre en el contexto de la actual crisis civilizatoria y que puede representar un rasgo característico del turismo del siglo XXI.

This study aimed to investigate the correlation between multislice computed tomography (MSCT)-derived parameters characterizing atrial enlargement and the frequency of emergency hospitalizations after catheter ablation for atrial fibrillation (AF).

En este artículo se analizan las narrativas de autoorganización de la población productora de milpa intercalada con árboles frutales (MIAF) en la región mazahua al noroeste del Estado de México. Se llevó a cabo un estudio cualitativo de tipo biográfico, mediante entrevistas a 13 productoras/es. Las y los productores MIAF fueron impulsados por actores externos desde 2018 y se les proporcionó semilla, material para la siembra y capacitaciones. Posteriormente, se autoorganizaron de tres formas: acción colectiva, interacción entre productoras/es y dependencia de recursos propios. Como limitantes están los costos en la producción de alimentos y las políticas públicas. Encontramos que las narrativas de autoorganización abonan a la discusión sobre la resiliencia socioecológica. Es importante que las y los productores MIAF potencien su acción colectiva para hacer frente a las adversidades, principalmente a la sequía. Tanto a nivel familiar como comunitario se pueden impulsar prácticas sostenibles destinadas a desarrollar la resiliencia.

The article aims to provide a brief historical background of the church of Santa Marina in Venice. The church was originally dedicated to San Liberale but underwent changes in both dedication and layout after the arrival of the sacred remains of the virgin monk in the lagoon. The text briefly outlines the hagiographic story of Santa Marina, the circumstances of the translatio of her body to Venice, and how her cult became part of the devotional, cultural, and civic identity of the city. The final section aims to integrate existing knowledge of the church’s layout transformation from the Middle Ages to the Modern Age with new data from unpublished sources. The objective is to reconstruct the interior of the sacred building that no longer exists, but whose external appearance can still be confirmed visually through Jacopo de’ Barbari’s view.

Background: Atrial fibrillation (AF) can often be triggered by an inflammatory substrate. Perivascular inflammation may be assessed nowadays using coronary computed tomography angiography (CCTA) imaging. The new pericoronary fat attenuation index (FAI HU) and the FAI Score have prognostic value for predicting future cardiovascular events. Our purpose was to investigate the correlation between pericoronary fat inflammation and the presence of AF among patients with coronary artery disease. Patients and methods: Eighty-one patients (mean age 64.75 ± 7.84 years) who underwent 128-slice CCTA were included in this study and divided into two groups: group 1 comprised thirty-six patients with documented AF and group 2 comprised forty-five patients without a known history of AF. Results: There were no significant differences in the absolute value of fat attenuation between the study groups (p > 0.05). However, the mean FAI Score was significantly higher in patients with AF (15.53 ± 10.29 vs. 11.09 ± 6.70, p < 0.05). Regional analysis of coronary inflammation indicated a higher level of this process, especially at the level of the left anterior descending artery (13.17 ± 7.91 in group 1 vs. 8.80 ± 4.75 in group 2, p = 0.008). Conclusions: Patients with AF present a higher level of perivascular inflammation, especially in the region of the left coronary circulation, and this seems to be associated with a higher risk of AF development.

Since August 2023, outbreaks of dengue virus (DENV) infection have occurred in Italy. We report 2 autochthonous case-patients and their extended follow-up. Despite persistent DENV detected in blood by PCR, results for antigenomic DENV RNA were negative after day 5, suggesting that a 5-day isolation period is adequate to avoid secondary cases.

The Covid-19 pandemic caused significant changes to teachers’ work, including a rapid switch to remote teaching. This increased the role of ICT in teachers’ work and made teachers susceptible to technostress. In this study, we aimed to identify ICT-related stressors (i.e., technostressors) in comprehensive school teachers’ work in Finland during the Covid-19 pandemic. The data, consisting of answers to two open-ended questions, were gathered as part of a questionnaire (n=361), and qualitative content analysis was applied. Based on the analysis, technostressors were divided into five categories: rapid ICT adoption, technological inadequacies, ICT-related pedagogical challenges, limitations in social interaction, and multichannel communication and availability pressure. The findings indicate that schools were not prepared for the pandemic-induced online teaching, which showed in inadequate resources and support for teachers. Moving forward, schools could reduce technostressors by, for example, organizing technical and pedagogical support, developing shared practices to decrease the digital communication load and availability pressure, and fostering interaction and collaboration in online environments.

Background: Cardiac arrest (CA) is the most severe complication of acute myocardial infarction (AMI). Besides the location and severity of coronary occlusion, different factors may have significant role in the pathogenesis of AMI-related cardiac arrest (CA), but their contribution is still under investigation. The aim of the study was to investigate the cardiac magnetic resonance (CMR) features of myocardial injury associated with a higher risk of CA accompanying an AMI.

Abstract Despite the successful deployment of efficacious vaccines and therapeutics, the development of novel vaccines for SARS-CoV-2 remains a major goal to increase vaccine doses availability and accessibility for lower income setting. We report here on the kinetics of Spike-specific humoral and T-cell response in young and old volunteers over 6 months follow-up after a single intramuscular administration of GRAd-COV2, a gorilla adenoviral vector-based vaccine candidate currently in phase-2 of clinical development. At all three tested vaccine dosages, Spike binding and neutralizing antibodies were induced and substantially maintained up to 3 months, to then contract at 6 months. Potent T-cell responses were readily induced and sustained throughout the study period, with only minor decline. No major differences in immune response to GRAd-COV2 vaccination were observed in the two age cohorts. In light of its favorable safety and immunogenicity, GRAd-COV2 is a valuable candidate for further clinical development and potential addition to the COVID-19 vaccine toolbox to help fighting SARS-CoV-2 pandemic.

El objetivo del trabajo es conocer la valorización social que las personas productoras campesinas asignan a los maíces pigmentados en el municipio de Ocoyoacac, Estado de México, el cual se distingue por tener localidades de proximidad a los mercados de especialización que demandan maíces azules y rojos: gastronómico, recreativo e industrial. Con base a dimensiones del enfoque de las percepciones sociales: cognitiva, conductual y afectiva, se realizó el estudio cualitativo con 16 entrevistas a profundidad y semiestructuradas. Se encontraron diferencias de género y generacionales en las percepciones sobre el trabajo que implican la producción tradicional y las prácticas agroecológicas. La valorización cognitiva y afectiva a la tierra, las semillas y la alimentación está ligada a esas diferenciaciones. El interés por vender el maíz pigmentado a los mercados de especialidad está condicionado a las experiencias previas con los sistemas de intermediación. En cambio, generaciones más jóvenes ven una oportunidad de desarrollo en estos mercados. Se concluye que las percepciones sociales de quienes conservan los maíces nativos como bien común deben ser los ejes analíticos de los estudios sobre mercados que buscan productos tradicionales.

COVID-19 patients show characteristic over-expression of different cytokines that may interfere with the interferon (IFN) response, delaying its production. Within the overexpressed cytokines, IL-8 plays a key role, and it may impede IFN-I activation. PBMC from eight healthy donors were exposed to 2019-nCoV/Italy-INMI1 isolate and supernatants/cells were collected at different time points; the production of either IFN-alpha or IL-8 was assessed. The same analysis was performed on plasma samples obtained from 87 COVID-19 patients. Antagonism between IFN-alpha and IL-8 was observed, since in those PBMC with medium or high IL-8 levels, IFN-α levels were low. The same scenario was observed in SARS-CoV-2-infected patients that were divided into three groups based on IL-8 low, medium and high levels; the correlation between low levels of IFN-α and high levels of IL-8 was statistically significant in both the IL-8 medium and IL-8 high group. Overall, our results showed a crosstalk/antagonism between IL-8 and IFN-alpha in PBMC from healthy donors challenged with SARS-CoV-2 and inversely proportional IFN-alpha levels to IL-8 concentrations detected in plasma samples from COVID-19 patients, suggesting that the impairment of the innate immune response in COVID-19 patients may be linked to a dysregulated cytokine response, namely through IL-8 production.

Objectives: To describe the trend of SARS-CoV-2 RNA in saliva samples from children attending nine schools in Rome in the local surveillance unit RM3 during the period of September 2021-March 2022, in parallel with the trend of SARS-CoV-2 RNA observed in nasopharyngeal swabs (NPSs) from the population in the same catchment area that was routinely tested at our laboratory in the same period. Methods: Saliva samples were collected using the Copan LolliSpongeTM device and analyzed by Aptima® SARS-CoV-2 Assay on the Panther® System. NPSs were tested using either Aptima® SARS-CoV-2 Assay or Alinity m SARS-CoV-2 Assay. Results: The percentage of positivity in the two populations was different; of the 2222 saliva samples from students, 0.99% had positive results, whereas the percentage was higher (33.43%) in the 8994 NPSs representing the population from local surveillance unit RM3. Interestingly, the trend of SARS-CoV-2 RNA in saliva samples from students was consistent with that observed in NPSs from the population in same catchment area, although with peaks slightly anticipated. Conclusion: Overall, screening of saliva in the schools represents a good system to monitor SARS-CoV-2 circulation in the population, allowing early detection and quick isolation of students who are asymptomatic with positive test results and thus prevention of virus transmission.

Abstract The new coronavirus SARS-CoV-2 is the causative agent of the COVID-19 pandemic, which so far has caused over 6 million deaths in 2 years, despite new vaccines and antiviral medications. Drug repurposing, an approach for the potential application of existing pharmaceutical products to new therapeutic indications, could be an effective strategy to obtain quick answers to medical emergencies. Following a virtual screening campaign on the most relevant viral proteins, we identified the drug raloxifene, a known Selective Estrogen Receptor Modulator (SERM), as a new potential agent to treat mild-to-moderate COVID-19 patients. In this paper we report a comprehensive pharmacological characterization of raloxifene in relevant in vitro models of COVID-19, specifically in Vero E6 and Calu-3 cell lines infected with SARS-CoV-2. A large panel of the most common SARS-CoV-2 variants isolated in Europe, United Kingdom, Brazil, South Africa and India was tested to demonstrate the drug’s ability in contrasting the viral cytopathic effect (CPE). Literature data support a beneficial effect by raloxifene against the viral infection due to its ability to interact with viral proteins and activate protective estrogen receptor-mediated mechanisms in the host cells. Mechanistic studies here reported confirm the significant affinity of raloxifene for the Spike protein, as predicted by in silico studies, and show that the drug treatment does not directly affect Spike/ACE2 interaction or viral internalization in infected cell lines. Interestingly, raloxifene can counteract Spike-mediated ADAM17 activation in human pulmonary cells, thus providing new insights on its mechanism of action. A clinical study in mild to moderate COVID-19 patients (NCT05172050) has been recently completed. Our contribution to evaluate raloxifene results on SARS-CoV-2 variants, and the interpretation of the mechanisms of action will be key elements to better understand the trial results, and to design new clinical studies aiming to evaluate the potential development of raloxifene in this indication.

Abstract Objective The objective of this study was to analyze gender inequalities and intersectionality experienced by rural-indigenous women who produce and sell native maize tortillas at three different markets-tianguis in central Mexico, facing the COVID-19 pandemic. Methods This was a qualitative study based on 36 in-depth interviews before pandemic (2018), as well as 16 interviews during pandemic (2020) of women engaged in this work. Results Making corn tortillas by hand is one of the culturally assigned gender roles in the indigenous population of the Mazahua region, which is why their sale in local markets as a female strategy to have access to income for household sustenance has been widely by the communities. The configuration of the different market-space for the sale of handmade tortillas, reflects the inequalities of gender and intersectionality (ethnicity, class, age, family life cycle and education levels). The women in conditions of poverty, landlessness, and with school-age children, have met greater disadvantages in continuing to sell tortillas in the face of the experience of pandemic restrictions. Conclusions The women who were already disadvantaged by their intersectional relationships continue to experience the same inequalities that conditioned their position in the marketplaces before the pandemic, sustaining a marginal but constant market.

When the Mpox virus (MPXV) began spreading globally in 2022, it became critical to evaluate whether residual immunity from smallpox vaccination provided cross-protection. To assess the cross-immune response to MPXV, we collected serum samples (n = 97) and PBMCs (n = 30) from healthy-donors, either born before 1974 and reporting smallpox vaccination during childhood or born after 1975 and not vaccinated with Vaccinia virus (VACV)-based vaccines. We evaluated the levels of anti-MPXV IgG and neutralizing antibodies (Nabs) and the presence of a T cell response against MPXV. We found anti-MPXV IgG and Nabs in 60 (89.6%) and 40 (70.1%) vaccinated individuals, respectively. We observed a T cell response to Orthopoxviruses and MPXV peptide pools in 30% of vaccinated individuals. We thus show that a high proportion of subjects who received the smallpox vaccine 40 to 60 years ago have humoral cross-immunity, while the T-cell-specific response against MPXV was observed in a smaller group (30%) of vaccinated individuals. This study, combined with information on immunity developed during natural infection or the administration of current vaccines, will contribute to a better understanding of humoral and cellular responses against MPXV.

Background: Identification of predictors for atrial fibrillation (AF) recurrence after pulmonary vein isolation (PVI) can lead to better long-term results. Our aim was to investigate the association between novel CT imaging markers reflecting the severity of coronary atherosclerosis and the risk of recurrence following PVI. Methods: This study included 80 patients with paroxysmal/persistent AF who underwent PVI. The patients were divided into two groups: Group 1–23 patients with recurrence and Group 2–57 patients without recurrence. Results: Patients with recurrence presented with a more enlarged left atrial diameter and reduced left ventricle EF, as assessed by echocardiography. Elevated calcium scores and right coronary artery (RCA) stenosis were correlated with a higher risk of AF recurrence (25.38 ± 4.1% vs. 9.76 ± 2.32%, p = 0.001). Patients with AF recurrence presented a higher left atrial volume index (LAVI) (61.38 ± 11.12 mm3/m2 vs. 46.34 ± 12.27 mm3/m2, p < 0.0001). The bi-atrial volume index (BAVI) was similarly higher in the AF recurrence group (98.23 ± 14.44 mm3/m2 vs. 76.48 ± 17.61 mm3/m2, p < 0.0001). Increased EAT volumes located around the LA (EAT-LA) were correlated with recurrence (25.55 ± 6.37 vs. 15.54 ± 8.44, p < 0.0001). Conclusions: RCA stenosis, together with atrial volumes and EAT-AS evaluated by CCTA, is associated with the risk of AF recurrence following PVI.

Lower respiratory tract infections (LRTIs) occur when there is a lower airway tract infection. They are well-known for increasing the susceptibility of patients to bacterial/fungal co-infections and super-infections. In this study, we present the results of our investigation, which involved 381 consecutive patients admitted to our hospital during the Influenza season from October 2022 to April 2023. Among the 381 specimens, 75 were bronchoalveolar (BAL), and 306 were nasopharyngeal swabs (NPSs). Notably, 34.4% of the examined samples tested positive for SARS-CoV-2. Of these, we observed that 7.96% of NPSs showed positivity only for other respiratory viruses, while a substantial percentage (77%) of BAL specimens exhibited positive results only for bacterial co-infections. The results of our study not only confirm the importance of co-infections in COVID-19 but also emphasize the significance of utilizing rapid diagnostic tests (RDTs) for the timely diagnosis of LRTIs. In fact, RDTs allow for the identification of multiple pathogens, providing clinicians with useful and timely information to establish effective therapy.

Abstract Autophagy is a highly dynamic and multi-step process, regulated by many functional protein units. Here, we have built up a comprehensive and up-to-date annotated gene list for the autophagy pathway, by combining previously published gene lists and the most recent publications in the field. We identified 604 genes and created main categories: MTOR and upstream pathways, autophagy core, autophagy transcription factors, mitophagy, docking and fusion, lysosome and lysosome-related genes. We then classified such genes in sub-groups, based on their functions or on their sub-cellular localization. Moreover, we have curated two shorter sub-lists to predict the extent of autophagy activation and/or lysosomal biogenesis; we next validated the “induction list” by Real-time PCR in cell lines during fasting or MTOR inhibition, identifying ATG14, ATG7, NBR1, ULK1, ULK2, and WDR45, as minimal transcriptional targets. We also demonstrated that our list of autophagy genes can be particularly useful during an effective RNA-sequencing analysis. Thus, we propose our lists as a useful toolbox for performing an informative and functionally-prognostic gene scan of autophagy steps.

Background and aims: At the Fiumicino Rome Airport, passengers can undergo the antigen or molecular test for SARS-CoV-2 at the COVID-19 Test Area (CTA), in compliance with the boarding regulations on air flights and those for entering the destination countries. The aim of this study was to describe the adaptability and usefulness of using rapid molecular tests designed for point of care (POC) in a context such as the CTA of Rome Fiumicino airport, by describing the volume and activities performed in the last period of the state of emergency in Italy, July 10, 2021- March 31, 2022. Materials and methods: Rapid molecular tests for SARS-CoV-2 were carried out with ID NOWTM COVID-19 assay on the ID NOWTM platform using dry swabs collected from passengers (or airport staff) at the CTA. Swabs were stored at room temperature and analyzed within 1-2 hours of collection. Sequencing for SARS-CoV-2 variants of concern (VOC) identification was carried out on swabs dipped in universal transport medium (UTM), after new swab gathering from consenting passengers resulted positive with the rapid molecular assay. A proficiency panel prepared with the viral isolate 2019-nCoV/Italy INMI1 was used to evaluate analytical sensitivity; clinical sensitivity was tested by performing real-time polymerase chain reaction (RT-PCR) tests on 50 swabs obtained from passengers who previously resulted positive to ID NOWTM COVID-19 assay. Results: In total, 14632 rapid molecular tests for SARS-CoV-2 were performed at CTA and 5.6% resulted positive. Sequence analysis of samples with Ct value

Mycobacterium abscessus (Mabs) is a dangerous non-tubercular mycobacterium responsible for severe pulmonary infections in immunologically vulnerable patients, due to its wide resistance to many different antibiotics which make its therapeutic management extremely difficult. Drug nanocarriers as liposomes may represent a promising delivery strategy against pulmonary Mabs infection, due to the possibility to be aerosolically administrated and to tune their properties in order to increase nebulization resistance and retainment of encapsulated drug. In fact, liposome surface can be modified by decoration with mucoadhesive polymers to enhance its stability, mucus penetration and prolong its residence time in the lung. The aim of this work is to employ Chitosan or ε-poly-L-lysine decoration for improving the properties of a novel liposomes composed by hydrogenated phosphatidyl-choline from soybean (HSPC) and anionic 1,2-Dipalmitoyl-sn-glycero-3-phosphorylglycerol sodium salt (DPPG) able to entrap Rifampicin. A deep physicochemical characterization of polymer-decorated liposomes shows that both polymers improve mucoadhesion without affecting liposome features and Rifampicin entrapment efficiency. Therapeutic activity on Mabs-infected macrophages demonstrates an effective antibacterial effect of ε-poly-L-lysine liposomes with respect to chitosan-decorated ones. Altogether, these results suggest a possible use of ε-PLL liposomes to improve antibiotic delivery in the lung.

The absence of scaffold protein Ambra1 leads to hyperproliferation and growth in mouse models. Here the authors show that Ambra1 deficiency accelerates melanoma growth and increases metastasis in mouse models of melanoma through FAK1 hyperactivation.

Diagnostic methods based on SARS-CoV-2 antigen detection are a promising alternative to SARS-CoV-2 RNA amplification. We evaluated the automated chemiluminescence-based Lumipulse® G SARS-CoV-2 Ag assay as compared to real time assays (combined results from RT-PCR Allplex™ SARS-CoV-2 assay and Easy SARS-CoV-2 WE kit) on 513 nasopharyngeal swabs (NPS). Among these, 53.6% resulted positive to RT-PCR, considered as the reference test. Compared to the reference test, overall sensitivity and specificity of Lumipulse® G SARS-CoV-2 Ag assay were 84.0%, and 89.1%, respectively, and overall agreement between the antigen and molecular assays was substantial (κ = 0.727). When stratifying samples into groups based on ranges of RT-PCR cycle threshold (Ct), the antigen test sensitivity was >95% for samples with Ct

Las contribuciones de la naturaleza a las personas son fundamentales para la vida y tienen efectos directos sobre el bienestar de la sociedad en su conjunto. El objetivo de este estudio fue analizar las percepciones de dichas contribuciones desde un enfoque de género a través de la Ecología Política Feminista. Se presenta la valoración de los beneficios que les brinda el bosque a comuneras y comuneros propietarios de un núcleo agrario ubicado enel Estado de México, cuyos recursos forestales maderables son aprovechados. Este estudio es una exploración cualitativa realizada mediante 35 entrevistas semiestructuradas: 13 a mujeres y 22 a hombres, donde se abordó el significado del bosque, la percepción sobre las contribuciones del bosque, los impulsores antropogénicos de cambio, así como propuestas para asegurar la disponibilidad de dichas contribuciones. Se encontraron discrepancias en la percepción de las contribuciones, las cuales se explican por las diferencias en la asignación de roles tradicionales de género y la división sexual del trabajo, que han permeado en la repartición, acceso a beneficios del bosque y su manejo. Se observa que las comuneras desarrollan una percepción sutil del cuidado del bosque como una forma de conservar sus relaciones armónicas con la naturaleza. Ello puede considerarse como una de las diferencias que permite acercar y valorar las percepciones sociales según el género para redefinir nuevos programas de acción en beneficio del bosque y del bienestar de las personas.

Background: Limited data are available about the predictors and outcomes associated with prolonged SARS-CoV-2 RNA shedding (VS). Methods: A retrospective study including COVID-19 patients admitted to an Italian hospital between March 1 and July 1, 2020. Predictors of viral clearance (VC) and prolonged VS from the upper respiratory tract were assessed by Poisson regression and logistic regression analyses. The causal relation between VS and clinical outcomes was evaluated through an inverse probability weighted Cox model. Results: The study included 536 subjects. The median duration of VS from symptoms onset was 18 days. The estimated 30-day probability of VC was 70.2%. Patients with comorbidities, lymphopenia at hospital admission, or moderate/severe respiratory disease had a lower chance of VC. The development of moderate/severe respiratory failure, delayed hospital admission after symptoms onset, baseline comorbidities, or D-dimer >1000 ng/mL at admission independently predicted prolonged VS. The achievement of VC doubled the chance of clinical recovery and reduced the probability of death/mechanical ventilation. Conclusions: Respiratory disease severity, comorbidities, delayed hospital admission and inflammatory markers negatively predicted VC, which resulted to be associated with better clinical outcomes. These findings highlight the importance of prompt hospitalization of symptomatic patients, especially where signs of severity or comorbidities are present.