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This article presents an innovative, parallel implementation of the Small BAseline Subset (SBAS) approach to automatically and efficiently process large volumes of multitemporal differential synthetic aperture radar (SAR) interferometry (DInSAR) interferograms generated at the native full spatial resolution of the SAR images. The starting point of the developed full-resolution parallel-SBAS (FR P-SBAS) technique involves some algorithmic extensions for improving the quality of the DInSAR time series to effectively analyze extended deformations and localized displacement phenomena, such as those affecting single buildings and infrastructures. The main focus of the work is on the efficient and scalable FR P-SBAS processing chain implementation, extensively exploiting graphical processing unit (GPU) architectures. Moreover, the presented scalability analysis demonstrates the GPU capability of efficiently generating full-resolution displacement time series starting from large DInSAR datasets. Furthermore, it is also shown that the implemented processing solution easily allows us to deal with SAR data acquired through the Stripmap and TOPS modes. To assess the quality of the generated DInSAR products, an extensive experimental analysis is also shown, based on long sequences of X-Band COSMO-SkyMed Stripmap and C-Band Sentinel-1 TOPS acquisitions relevant to the Campi Flegrei Caldera (Southern Italy), which is monitored through a dense GNSS network. The presented results demonstrate the effectiveness of the FR P-SBAS processing chain in retrieving multifrequency and multiplatform displacement time series at the full spatial resolution with subcentimetric accuracy and in very short time frames, from a few hours for the COSMO-SkyMed datasets up to some tens of hours for the Sentinel-1 case.

We present in this work the new advances of the differential synthetic aperture radar (SAR) interferometry (DInSAR) technique referred to as the parallel Small BAseline Subset (P-SBAS) approach for the generation of displacement time series from the recently available L-band SAR image sequences acquired by the Argentinian SAOCOM-1 constellation. In particular, we first discuss the algorithmic extensions allowing us to retrieve SAOCOM-1 DInSAR products, with a main focus on the exploitation of Stripmap SAR images and multilook interferograms. These algorithmic improvements are relevant to the adjacent single look complex (SLC) image slices merging to the multitemporal residual orbital artifacts mitigation and to the phase unwrapping procedure enhancement. Subsequently, the effectiveness of the extended P-SBAS processing chain is shown through a comparative analysis between the achieved SAOCOM-1 DInSAR results and the corresponding ones relevant to Sentinel-1 and COSMO-SkyMed acquisitions. Moreover, a comparison between the SAOCOM-1 displacement time series and the GNSS measurements, relevant to the Campi Flegrei Caldera (Italy), is presented. This shows that the mean standard deviation value of the differences between the DInSAR and the GNSS time series, the latter projected in the radar line of sight, is about 1 cm, further confirming the effectiveness of the P-SBAS processing chain extension.

Hemophagocytic lymphohistiocytosis (HLH) is a serious haematologic condition that can be related to various diseases, including tuberculosis (TB). The patient is a previously healthy 26-year-old man, originally from western Africa, admitted to hospital for fever and weight loss. Given the results of a computed tomography (CT) scan, ocular examination and microbiologic tests, miliary TB with pulmonary, lymph nodal and ocular involvement was diagnosed. Following the introduction of antitubercular treatment (ATT), an increase in inflammation indexes and severe pancytopenia were observed; at this point, the patient presented with six of the eight diagnostic criteria for HLH, and a diagnosis of HLH secondary to TB was raised. Therefore, HLH treatment with a high dose of dexamethasone was started, with a good clinical response. We performed a literature review of TB-related HLH, which shows a high mortality rate. ATT is necessary to ensure patient survival to remove the antigenic driver. Our patient developed HLH after the initiation of ATT as a paradoxical reaction, which may be linked to the release of antigens due to the bactericidal effect of ATT.

BackgroundFrailty, a geriatric syndrome associated with adverse outcomes, lacks a universal definition. No consensus exists on the most effective frailty scale for predicting mortality.MethodsThis prospective observational study followed community-dwelling volunteers for 6 years. Frailty was measured with the Frailty Index (FI) and the Frailty Phenotype (FP). Concordance was assessed using Cohen’s Kappa coefficients. Age-and sex-adjusted Cox regression analyses were conducted to evaluate the association with mortality.ResultsOut of 1,114 participants (median age 72 years, IQR 69–77), 186 were classified as frail by the FI, 13 by the FP and 48 by both definitions. The concordance between the two measures was fair (κ = 0.26). Thirty-nine individuals died during the follow-up period. The FI showed a stronger association with mortality (HR 75.29, 95% CI 8.12–697.68, p

Abstract Background The ageing process is characterized by a change of body composition with an increase of fat mass and a reduction of muscle mass. Above a certain threshold these alterations configure a condition named sarcopenic obesity (SO). SO is associated with physical frailty in Asian and Brazilian populations. SO impacts on physical frailty in other ethnic groups but its influence on general frailty which is multidimensional and includes cognitive, social and physical factors, remain insufficiently explored in the Italian population. Methods Frailty was measured in community dwelling Italian older adults enrolled in the FRASNET study with the frailty index (FI). The FI quantifies frailty as the ratio of the number of present health deficits to the total number of health deficits considered. Regression analyses were performed to assess the association between body composition categories and frailty. Classification and regression tree models were run to evaluate the frailty predictors. Results One Thousand One Hundred Fourteen participants of the FRASNET study were included in the present analysis. The sample was composed for the 60.5% by females and its median age was 72 years. The median FI score was 0.11 (IQR 0.07–0.20); 234 individuals (21%) were frail (FI ≥ 0.25). SO (B 0.074, 95% C.I. 0.05–0.1, p

BackgroundObesity and frailty are prevalent geriatric conditions that share some pathophysiological mechanisms and are associated with adverse clinical outcomes. The relationship between frailty, obesity, and polymorphism remains inadequately explored. Single nucleotide polymorphisms (SNPs) offer insights into genetic predispositions that may influence the development of both frailty and obesity.MethodsWe aimed at investigating whether SNPs associated with frailty also play a role in obesity. Data were collected from the FRASNET cross-sectional study, which included community-dwelling older individuals residing in Milan and nearby areas. Participants were recruited through random sampling. They underwent multidimensional geriatric assessments, which included the collection of blood samples for SNP analysis. Frailty was assessed using the frailty index, and body composition was evaluated using bioelectrical impedance analysis and anthropometric measures.ResultsSNPs related to frailty and linked to the renin–angiotensin system (CYP11B2 rs1799998, AGT rs5051, and AGTR1 rs2131127), apoptosis pathways (CASP8 rs6747918), growth hormone signaling (GHR rs6180), inflammation (TLR4 rs5030717, CD33 rs3865444, and FN1 rs7567647), adducin (ADD3 rs3731566), and the 9p21–23 region (rs518054) were found to be associated with various measures of obesity in community-dwelling older adults.ConclusionsFrailty-related SNPs contribute to obesity in community-dwelling older adults. We identified a novel association between adducin SNPs and visceral fat, which has not been previously reported. Detecting genetic predispositions to obesity and frailty early could aid in identifying individuals at risk, facilitating the adoption of preventive interventions. This represents an initial step toward promoting early intervention strategies.

Campi Flegrei caldera is an Italian high-risk volcano experiencing a progressively more intense long-term uplift, accompanied by increasing seismicity and geochemical emissions over the last two decades. Ground deformation shows an axisymmetric bell-shaped pattern, with a maximum uplift of about 120 cm, from 2005, in the caldera central area. We analyzed Sentinel-1 and COSMO-SkyMed Multi-Temporal DInSAR measurements and GNSS data to reveal and investigate a geodetic anomaly that has clearly manifested since 2021, locally deviating from the typical bell-shaped deformation pattern. This anomaly is located east of Pozzuoli town, in the Mt. Olibano–Accademia area, covers an area of about 1.3 km2 and shows, in comparison to surrounding areas, a maximum uplift deficit of about 9 cm between 2021 and 2023. To investigate the anomaly causes, we analyzed the caldera seismicity and inverted the DInSAR data to determine the primary source of the ground deformation pattern, which is consistent with a penny-shaped source located approximately 3800 m beneath the Pozzuoli town, with a radius of about 1200 m. We also found that the time evolution of the uplift deficit in the geodetic anomaly area correlates well with the earthquake occurrence, with the greater magnitude events clustering in this area. These considerations suggest the geodetic anomaly is a local response to the tensile stress regime produced by the inflating primary deformation source. This phenomenon can be influenced by the Mt. Olibano–Accademia lava domes lithological heterogeneities that may induce a localized reaction to ground deformation during the inflationary phase. Our interpretation aligns with the concentration of earthquakes and hydrothermal fluid emissions in this area, indicating the presence of faults, fractures, and fluid circulation. Accordingly, the geodetic anomaly area represents a zone of crustal weakness that requires careful monitoring and study.

«Gli istanti si susseguono gli uni agli altri: nulla conferisce loro l'illusione di un contenuto o la parvenza di un significato; si svolgono; il loro corso non è il nostro; prigionieri di una percezione inebetita, li guardiamo passare; il vuoto del cuore dinanzi al vuoto del tempo: due specchi, uno di fronte all’altro, che riflettono la loro assenza, una stessa immagine di nullità... Come sotto l’effetto di un’idiozia sognante, ogni cosa si livella: niente più cime, niente più abissi... Dove scoprire la poesia delle menzogne, il pungolo di un enigma?» (Cioran 1996, p. 26). In questa “convalescenza incurabile” guidata dalla noia, ci si chiede in che modo, in una realtà in cui «i dati e le informazioni non possiedono alcuna forza simbolica, per cui non consentono il riconoscimento» (Chul Han 2021, p. 12), il Monumento possa imprimere nella memoria un determinato evento.

Background: Despite the well-known efficacy of anti-COVID-19 vaccines in preventing morbidity and mortality, several vaccinated individuals are diagnosed with SARS-CoV-2 breakthrough infection, which might require hospitalisation. This multicentre, observational, and retrospective study aimed to investigate the clinical characteristics and outcomes of vaccinated vs. non-vaccinated patients, both hospitalised with SARS-CoV-2 infection in 3 major hospitals in Northern Italy. Methods: Data collection was retrospective, and paper and electronic medical records of adult patients with a diagnosed SARS-CoV-2 infection were pseudo-anonymised and analysed. Vaccinated and non-vaccinated individuals were manually paired, using a predetermined matching criterion (similar age, gender, and date of hospitalisation). Demographic, clinical, treatment, and outcome data were compared between groups differing by vaccination status using Pearson’s Chi-square and Mann-Whitney tests. Moreover, multiple logistic regression analyses were performed to assess the impact of vaccination status on ICU admission or intra-hospital mortality. Results: Data from 360 patients were collected. Vaccinated patients presented with a higher prevalence of relevant comorbidities, like kidney replacement therapy or haematological malignancy, despite a milder clinical presentation at the first evaluation. Non-vaccinated patients required intensive care more often than their vaccinated counterparts (8.8% vs. 1.7%, p = 0.002). Contrariwise, no difference in intra-hospital mortality was observed between the two groups (19% vs. 20%, p = 0.853). These results were confirmed by multivariable logistic regressions, which showed that vaccination was significantly associated with decreased risk of ICU admission (aOR=0.172, 95%CI: 0.039–0.542, p = 0.007), but not of intra-hospital mortality (aOR=0.996, 95%CI: 0.582–1.703, p = 0.987). Conclusions: This study provides real-world data on vaccinated patients hospitalised with COVID-19 in Northern Italy. Our results suggest that COVID-19 vaccination has a protective role in individuals with higher risk profiles, especially regarding the need for ICU admission. These findings contribute to our understanding of SARS-CoV-2 infection outcomes among vaccinated individuals and emphasise the importance of vaccination in preventing severe disease, particularly in those countries with lower first-booster uptake rates.

Autosomal dominant polycystic kidney disease (ADPKD) is the most common genetic kidney disease. It is characterized by the formation of cysts in kidneys. This condition has a significant impact on people’s lives. It causes not only physical suffering but also psychological suffering. People with ADPKD may experience psychological distress, depending on their personal and health conditions. The inability to accept or adapt to the disease and its resulting changes causes individuals difficulties that appear in different levels of their lives: intrapersonal, interpersonal, social, and occupational. In the context of ADPKD, the psychologist is involved both at clinical and research levels. The psychologist has a crucial role in supporting patients by assessing how they react to the disease, to its related limitations, and to the resulting disabilities. The proposal of psychological support, considered as an intervention instrument, is helpful both at the diagnostic stage and in follow-up, as the disease worsens. The support aims to encourage acceptance and adaptation to the disease, process changes, and physical and mental consequences.

Folic acid insufficiency is an important risk factor for congenital neural tube defects. Despite recommendations and national campaigns, the proportion of women taking folic acid in the peri-conceptional period remains insufficient worldwide. We describe in this study the proportion of peri-conceptional folic acid supplementation use and its determinants among a population of hospital workers during the course of a prevention campaign. We performed a single-center cross sectional study in a university hospital in France. Data were collected during 2 months in 2019 by an online questionnaire sent to all professionals. We collected information about folic acid supplementation use, its modalities (form, period, frequency and dosage) and reason for initiating or not supplementation. Response rate was 11.4 % (n = 1,075/9,447). Among the 748 women who reported at least one pregnancy, 72.7 % (95 % CI: 69.4–76.0 %) reported taking folic acid during their last pregnancy. Main reason for initiating supplementation was information given by a health professional (87.8 %), especially by gynaecologists-obstetricians. Principal factors associated with folic acid supplementation use were age between 25 and 35 years, high level of education and recent pregnancy. Folic acid supplementation use is still not systematic before and during pregnancy, even among health professionals. There is a case for mandatory folic acid fortification for the French general population.

The oxidative-stress-elicited deterioration of chondrocyte function is the initial stage of changes leading to the disruption of cartilage homeostasis. These changes entail a series of catabolic damages mediated by proinflammatory cytokines, MMPs, and aggrecanases, which increase ROS generation. Such uncontrolled ROS production, inadequately balanced by the cellular antioxidant capacity, eventually contributes to the development and progression of chondropathies. Several pieces of evidence show that different growth factors, single or combined, as well as anti-inflammatory cytokines and chemokines, can stimulate chondrogenesis and improve cartilage repair and regeneration. In this view, hypothesizing a potential growth-factor-associated action, we investigate the possible protective effect of post-operation knee fluid from patients undergoing prosthesis replacement surgery against ROS-induced damage on normal human knee articular chondrocytes (HKACs). To this end, HKACs were pre-treated with post-operation knee fluid and then exposed to H2O2 to mimic oxidative stress. Intracellular ROS levels were measured by using the molecular probe H2DCFDA; cytosolic and mitochondrial oxidative status were assessed by using HKACs infected with lentiviral particles harboring the redox-sensing green fluorescent protein (roGFP); and cell proliferation was determined by measuring the rate of DNA synthesis with BrdU incorporation. Moreover, superoxide dismutase (SOD), catalase, and glutathione levels from the cell lysates of treated cells were also measured. Postoperative peripheral blood sera from the same patients were used as controls. Our study shows that post-operation knee fluid can counteract H2O2-elicited oxidative stress by decreasing the intracellular ROS levels, preserving the cytosolic and mitochondrial redox status, maintaining the proliferation of oxidatively stressed HKACs, and upregulating chondrocyte antioxidant defense. Overall, our results support and propose an important effect of post-operation knee fluid substances in maintaining HKAC function by mediating cell antioxidative system upregulation and protecting cells from oxidative stress.

Background/Aims: The new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes a wide spectrum of effects, including acute kidney injury (AKI) in up to 40% of hospitalized patients. Given the established relationship between AKI and poor prognosis, whether AKI might be a prognostic indicator for patients admitted to the hospital for SARS-CoV-2 infection would allow for a straightforward risk stratification of these patients. Methods: We analyzed data of 623 patients admitted to San Raffaele Hospital (Milan, IT) between February 25 and April 19, 2020, for laboratory-confirmed SARS-CoV-2 infection. Incidence of AKI at hospital admission was calculated, with AKI defined according to the KDIGO criteria. Multivariable Cox regression models assessed the association between AKI and overall mortality and admission to the intensive care unit (ICU). Results: Overall, 108 (17%) patients had AKI at hospital admission for SARS-CoV-2 infection. After a median follow-up for survivors of 14 days (interquartile range: 8, 23), 123 patients died, while 84 patients were admitted to the ICU. After adjusting for confounders, patients who had AKI at hospital admission were at increased risk of overall mortality compared to those who did not have AKI (hazards ratio [HR]: 2.00; p = 0.0004), whereas we did not find evidence of an association between AKI and ICU admission (HR: 0.95; p = 0.9). Conclusions: These data suggest that AKI might be an indicator of poor prognosis for patients with SARS-CoV-2 infection, and as such, given its readily availability, it might be used to improve risk stratification at hospital admission.

Abstract Purpose The aim of this study was to assess how physicians perceive the role of the reimbursement system and its potential influence in affecting their treatment choice in the management of patients affected by osteoarthritis (OA). Methods A survey was administered to 283 members of SIAGASCOT (Italian Society of Arthroscopy, Knee, Upper Limb, Sport, Cartilage and Orthopaedic Technologies), a National scientific orthopaedic society. The survey presented multiple choice questions on the access allowed by the current Diagnosis‐Related Groups (DRG) system to all necessary options to treat patients affected by OA and on the influence toward prosthetic solutions versus other less invasive options. Results Almost 70% of the participants consider that the current DRG system does not allow access to all necessary options to best treat patients affected by OA. More than half of the participants thought that the current DRG system favors the choice of prosthetic solutions (55%) and that it can contribute to the increase in prosthetic implantation at the expense of less invasive solutions (54%). The sub‐analyses based on different age groups, professional roles, and places of work allowed to evaluate the response in each specific category, confirming the findings for all investigated aspects. Conclusions This survey documented that the majority of physicians consider that the reimbursement system can influence the treatment choice when managing OA patients. The current DRG system was perceived as unbalanced in favor of the choice of the prosthetic solution, which could contribute to the increase in prosthetic implantation at the expense of other less invasive options for OA management.

Abstract Purpose The aim of this work was to retrospectively analyze the clinical, subjective, and radiological results of medial closing-wedge distal femur osteotomy (MCW-DFO) for the treatment of osteoarthritis (OA) in valgus knee at medium- to long-term follow-up. Materials and methods A total of 57 patients (62 knees) treated with MCW-DFO between 1984 and 2018 were included in the study. Patient age at the time of the surgery ranged between 28 and 61 years (average: 48 years). All patients with a minimum follow-up of 4 years were contacted to request for them to undergo clinical, subjective, and radiological evaluation. Preoperative hip–knee–ankle (HKA) angle (i.e., preoperative valgus malalignment) was 8.6° ± 2°. Patients were evaluated using the following scales: the Knee Injury and Osteoarthritis Outcome Score (KOOS), the Knee Society Score (KSS), the International Knee Documentation Committee (IKDC), the Visual Analog Scale (VAS), and the Numeric Rating Scale 11 (NRS-11). Results Mean follow-up was 11.6 ± 4.9 years, and a total of 17 patients (20 knees) were available for the last examination. At maximum follow-up, 4 patients underwent conversion to a total knee replacement (20%); their survival rate was 100% at 10 years and 66.7% at 15 years, as estimated using the Kaplan–Meier curve. The subjective Knee Society Score improved on average from 37.7 ± 10 to 63.9 ± 15.4. The objective Knee Society Score improved on average from 42.2 ± 11.7 to 75 ± 22.5. The pain detected through the VAS and NRS-11 scales improved from 56.7 ± 12.9 to 42 ± 17.1 and from 5.8 ± 1.1 to 4.4 ± 1.7, respectively. Thirteen patients (70%) required hardware removal at an average time of 19 ± 4 months due to a local nuisance. Conclusions MCW-DFO can improve symptoms in patients with osteoarthritis in a valgus knee at medium- to long-term follow-up, reducing the progression of osteoarthritis in properly selected patients.

Abstract SARS-CoV-2 virus infection is responsible for coronavirus disease (COVID-19), which is characterised by a hyperinflammatory response that plays a major role in determining the respiratory and immune-mediated complications of this condition. While isolating peripheral blood mononuclear cells (PBMCs) from whole blood of COVID-19 patients by density gradient centrifugation, we noticed some changes in the floating properties and in the sedimentation of the cells on density medium. Investigating this further, we found that in early phase COVID-19 patients, characterised by reduced circulating lymphocytes and monocytes, the PBMC fraction contained surprisingly high levels of neutrophils. Furthermore, the neutrophil population exhibited alterations in the cell size and in the internal complexity, consistent with the presence of low density neutrophils (LDNs) and immature forms, which may explain the shift seen in the floating abilities and that may be predictive of the severity of the disease. The percentage of this subset of neutrophils found in the PBMC band was rather spread (35.4 ± 27.2%, with a median 28.8% and IQR 11.6–56.1, Welch’s t-test early phase COVID-19 versus blood donor healthy controls P

El propósito de este artículo es revisar la literatura periodística de mujeres a inicios del siglo XX. Esta es un instrumento de análisis del pensamiento colectivo que la intelectual mujer poseía y que determinó —tanto de manera directa como indirecta— los futuros cambios socioculturales. Durante las dos primeras décadas del siglo XX, las intelectuales trabajaron un tema de fondo: el acceso de la mujer a la educación y a un trabajo digno. Esta temática fue planteada desde distintos puntos de vista, los cuales generaron debates y rivalidades entre las mismas enunciantes. Este estudio gira alrededor del artículo de Mercedes Cabello de Carbonera, “Los exámenes”.

Understanding how geography and human mobility shape the patterns and spread of infectious diseases such as COVID-19 is key to control future epidemics. An interesting example is provided by the second wave of the COVID-19 epidemic in Europe, which was facilitated by the intense movement of tourists around the Mediterranean coast in summer 2020. The Italian island of Sardinia is a major tourist destination and is widely believed to be the origin of the second Italian wave. In this study, we characterize the genetic variation among SARS-CoV-2 strains circulating in northern Sardinia during the first and second Italian waves using both Illumina and Oxford Nanopore Technologies Next Generation Sequencing methods. Most viruses were placed into a single clade, implying that despite substantial virus inflow, most outbreaks did not spread widely. The second epidemic wave on the island was actually driven by local transmission of a single B.1.177 subclade. Phylogeographic analyses further suggest that those viral strains circulating on the island were not a relevant source for the second epidemic wave in Italy. This result, however, does not rule out the possibility of intense mixing and transmission of the virus among tourists as a major contributor to the second Italian wave.

Earth observation data are useful to analyze the impact of climate-related variables on geomorphological processes. This work aims at evaluating the impact of rainfall on slow-moving landslides, by means of a quantitative procedure for identifying satellite-based displacement clusters, comparing them with rainfall series, and applying statistical tests to evaluate their relationships at the regional scale. The chosen study area is the Basento catchment in the Basilicata region (southern Italy). Rainfall series are gathered from rain gauges and are analyzed to evaluate the presence of temporal trends. Ground displacements are obtained by applying the P-SBAS (Parallel Small BAseline Subset) to three datasets of Sentinel-1 images: T146 ascending orbit, and T51 and T124 descending orbits, for the period 2015–2020. The displacement series of the pixels located in areas mapped as landslides by the Italian Landslide Inventory and sited within rain gauge influence regions (defined as 10 km circular buffers) are studied. Those displacement series are analyzed and compared to the rainfall series to search for correlations, by employing statistical and non-parametric tests. In particular, two landslides are selected and investigated in detail. Significant results were obtained for the T124 descending orbit for both landslides, for a 3-day cumulative rainfall and a 7-day delay of the slope response. Challenges in the whole procedure are highlighted and possible solutions to overcome the raised problems are proposed. Given the replicability of the proposed quantitative procedure it might be applied to any study area.

Abstract Background Articular cartilage lacks a regenerative response. Embryonic stem cells (ESCs) are a source of pluripotent cells for cartilage regeneration. Their use, however, is associated with a risk of teratoma development, which depends on multiple factors including the number of engrafted cells and their degree of histocompatibility with recipients, the immunosuppression of the host and the site of transplantation. Colonies of sheep embryonic stem-like (ES-like) cells from in vitro-produced embryos, positive for stage-specific embryonic antigens (SSEAs), alkaline phosphatase (ALP), Oct 4, Nanog, Sox 2 and Stat 3 gene expression, and forming embryoid bodies, were pooled in groups of two-three, embedded in fibrin glue and engrafted into osteochondral defects in the left medial femoral condyles of 3 allogeneic ewes (ES). Empty defects (ED) and defects filled with cell-free glue (G) in the condyles of the controlateral stifle joint served as controls. After euthanasia at 4 years post-engraftment, the regenerated tissue was evaluated by macroscopic, histological and immunohistochemical (collagen type II) examinations and fluorescent in situ hybridization (FISH) assay to prove the ES-like cells origin of the regenerated tissue. Results No teratoma occurred in any of the ES samples. No statistically significant macroscopic or histological differences were observed among the 3 treatment groups. FISH was positive in all the 3 ES samples. Conclusions This in vivo preclinical study allowed a long-term evaluation of the occurrence of teratoma in non-immunosuppressed allogeneic adult sheep engrafted with allogeneic ES-like cells, supporting the safe and reliable application of ES cells in the clinic.

Objectives To evaluate an algorithm developed for identifying non-small cell lung cancer (NSCLC) candidates among patients with lung cancer with a diagnosis International Classification of Diseases: ninth revision (ICD-9) 162.x code in administrative databases. Algorithm could then be applied for identifying the NSCLC population in order to assess the appropriateness and quality of care of the NSCLC care pathway.Design Algorithm discrimination capacity to select both NSCLC or non-NSCLC was carried out on a sample for which electronic health record (EHR) diagnosis was available. A bivariate frequency distribution and other measures were used to evaluate algorithm’s performances. Associations between possible factors potentially affecting algorithm accuracy were investigated.Setting Administrative databases used in a specific geographical area of Emilia-Romagna region, Italy.Participants Algorithm was carried out on patients aged >18 years, with a lung cancer diagnosis from January to December 2017 and resident in Emilia-Romagna region who have been hospitalised at IRST or in one of the hospitals placed in the Forlì-Cesena area and for which EHR diagnosis data were available.Outcome measures Overall accuracy, positive (PPV) and negative (NPV) predictive values, sensitivity and specificity, positive and negative likelihood ratios and diagnostic OR were calculated.Results A total of 430 patients were identified as lung cancer cases based on ICD-9 diagnosis. Focusing on the total incident cases (n=314), the algorithm had an overall accuracy of 82.8% with a sensitivity of 88.8%. The analysis confirmed a high level of PPV (90.2%), but lower specificity (53.7%) and NPV (50%). Higher length of stay seemed to be associated with a correct classification. Hospitalisation regimen and a supply of antiblastic therapy seemed to increase the level of PPV.Conclusion The algorithm demonstrated a strong validity for identifying NSCLC among patients with lung cancer in hospital administrative databases and can be used to investigate the quality of cancer care for this population.Trial registration number NCT04676321.

Inbreeding depression has been observed in many different species, but in humans a systematic analysis has been difficult so far. Here, analysing more than 1.3 million individuals, the authors show that a genomic inbreeding coefficient (FROH) is associated with disadvantageous outcomes in 32 out of 100 traits tested.

BackgroundSevere acute respiratory syndrome coronavirus 2 is a recently discovered pathogen responsible of coronavirus disease 2019 (COVID-19). The immunological changes associated with this infection are largely unknown.MethodsWe evaluated the peripheral blood mononuclear cells profile of 63 patients with COVID-19 at diagnosis. We also assessed the presence of association with inflammatory biomarkers and the 28-day mortality.ResultsLymphocytopenia was present in 51 of 63 (80.9%) patients, with a median value of 720 lymphocytes/µl (IQR 520-1,135). This reduction was mirrored also on CD8+ (128 cells/µl, IQR 55-215), natural killer (67 cells/µl, IQR 35–158) and natural killer T (31 cells/µl, IQR 11–78) cells. Monocytes were preserved in total number but displayed among them a subpopulation with a higher forward and side scatter properties, composed mainly of cells with a reduced expression of both CD14 and HLA-DR. Patients who died in the 28 days from admission (N=10, 15.9%), when compared to those who did not, displayed lower mean values of CD3+ (337.4 cells/µl vs 585.9 cells/µl; p=0.028) and CD4+ cells (232.2 cells/µl vs 381.1 cells/µl; p=0.042) and an higher percentage of CD8+/CD38+/HLA-DR+ lymphocytes (13.5% vs 7.6%; p=0.026).DiscussionThe early phases of COVID-19 are characterized by lymphocytopenia, predominance of Th2-like lymphocytes and monocytes with altered immune profile, which include atypical mononuclear cells.

Keup and colleagues provide liquid biopsy preliminary results by sequencing variants in circulating tumor cells (CTCs) and cell-free deoxyribonucleic acid (cfDNA) “all from one tube” format, in order to use the same blood sample under the same isolation conditions of both analytes to reach an unbiased comparability and consistency. We appreciated the attempt of the authors to improve technical procedures in liquid biopsy research area, but we wanted to raise several issues related to cfDNA detection, reporting our research experience. This is a feasibility study as the authors analyzed only one sample from a small case series at an advanced line of treatment. In the clinical practice to monitor the disease and predict the treatment response, the analysis should be done at multiple time points. We have previously demonstrated that the quantity and the integrity of the cfDNA are not useful to determine the evolution of early breast cancer (bc), maybe due to the fact that cfDNA is not strictly related to cancer but also to an inflammatory status. Given that a high content of cfDNA could reflect inflammatory processes, we decided to investigate the role of stimulator of interferon gene (STING), an important regulator of cancer cell growth and senescence, in bc tissue in relation to cfDNA. STING biomarker analyzed by immunohistochemistry on tumor tissue could reflect a circulating inflammatory status and needs to be further investigated, not only on CTCs but also on cfDNA. One of the major issues of cfDNA is to decide what to analyze on it, in terms of type of cells and genetic alterations. Considering that multiple tests could be done to study gene copy number alterations, mutations, and variant fusions, the proper molecular test should be chosen, on the basis of the clinical need, starting from the treatment choice to disease monitoring.

In late December 2019, some patients were hospitalized with an initial diagnosis of pneumonia of unknown etiology. These patients were epidemiologically linked to a wholesale market of seafood, wild animals and meat located in Wuhan, Hubei province, China. Acute respiratory disease caused by a new Coronavirus SARS-CoV-2, formerly known as 2019-nCoV, afterwards as Coronavirus disease 2019 (COVID-19), spread throughout China and received the attention of the entire world. Analysis of the genomic sequence of COVID-19 showed 88% of identity with two bat-derived severe acute respiratory syndrome-like Coronaviruses. Illegal and sustainable wildlife trade is the second largest direct threat to species after habitat destruction. Each year, hundreds of millions of plants and animals are captured or collected in the wild to be sold as food, pets, medicines, ornaments and for a variety of other reasons. Even the climate crisis could offer dangerous scenarios in addition to another fundamental chapter of the environmental pillar which is the one concerning air quality. There is a solid scientific literature which correlates the incidence of viral infection cases with concentrations of atmospheric particulate matter (e.g. PM10 and PM2.5). Despite the current regulations, which limit the levels of certain atmospheric pollutants, there are still numerous negative health effects deriving from exposure to these agents. However, it can be said that chronic air pollution, such as peaks of concentration of fine dust and other pollutants, acts as a pejorative factor in cases of epidemics. (GCND_planet)

Abstract Background Mediterranean farmers traditionally utilized plants, animals, and minerals sourced locally to treat their animals. Research is needed to understand at what extent such knowledge of domestic animal care still survives and to document such traditions for further developments. Methods We carried out our field study to recover ancient ethno-veterinary practices by means of questionnaires and interviews to farmers in rural areas of the Mediterranean island of Sardinia (Italy). Quantitative indices were used to evaluate the distribution and diversity of the acquired information. Results We report here 98 sources (42 plant taxa, 14 animal-based substances, 15 minerals, and 27 other materials of various origin) emerged from the survey for the care of 41 ailments of cattle, pigs, and horses. Ethno-veterinary treatments, detailed in their formulations and applications, were used against ecto- and endo-parasites, gastrointestinal diseases, heart diseases, viral and bacterial diseases, wounds, sprains, and bruises. Conclusion Our survey can be useful to implement the use of phyto-therapeutics and other remedies of non-herbal origin for diseased animals, and, as elderly farmers held most of the knowledge, it can contribute to the conservation of Mediterranean ethno-veterinary knowledge.

The SARS-CoV2 pandemic forced an abrupt interruption of social contacts and interpersonal affective relationships all over the world, according to national directives. Many considerable inconveniences occurred with important repercussions also on the emotional state of people and their pets. We carried out a national survey to evaluate the human-dog relationship in a social isolation context using an adapted version of Monash Dog Owner Relationship Scale, the perception of the dogs’ discomfort by their human owners, and the resilience of the dog through the quantification of symptoms, in time of the first lockdown of the COVID-19 pandemic. The results highlighted that the human-dog interaction was similar during quarantine; however, there was lower owner’s perception of a dog’s cost during the quarantine than before it.

Abstract The inhibition of ENaC may have therapeutic potential in CF airways by reducing sodium hyperabsorption, restoring lung epithelial surface fluid levels, airway hydration and mucociliary function. The challenge has been to deliver siRNA to the lung with sufficient efficacy for a sustained therapeutic effect. We have developed a self-assembling nanocomplex formulation for siRNA delivery to the airways that consists of a liposome (DOTMA/DOPE; L), an epithelial targeting peptide (P) and siRNA (R). LPR formulations were assessed for their ability to silence expression of the transcript of the gene encoding the α-subunit of the sodium channel ENaC in cell lines and primary epithelial cells, in submerged cultures or grown in air-liquid interface conditions. LPRs, containing 50 nM or 100 nM siRNA, showed high levels of silencing, particularly in primary airway epithelial cells. When nebulised these nanocomplexes still retained their biophysical properties and transfection efficiencies. The silencing ability was determined at protein level by confocal microscopy and western blotting. In vivo data demonstrated that these nanoparticles had the ability to silence expression of the α-ENaC subunit gene. In conclusion, these findings show that LPRs can modulate the activity of ENaC and this approach might be promising as co-adjuvant therapy for cystic fibrosis.

BACKGROUND: Autosomal dominant polycystic kidney disease is the most common inherited renal disease and affects less than 1 every 400-1,000 people. There are many effective treatments, including blood pressure management, physical activity, low sodium diet and hydration. Therapeutic education is part of a patient’s care and treatment. This approach is an essential strategy in order to face the current healthcare scenario, in which the number of people affected by chronic diseases is progressively increasing. OBJECTIVES: This article aims to analyze the effect of therapeutic education in patients with ADPKD, the level of adherence to pharmacological therapy and their compliance to dietetic and lifestyle recommendations as part of a nursing-led education. METHODS: This is a prospective, longitudinal, observational pilot study. The following measurements were used: Kidney Disease Quality of life - Short Form, Hospital Anxiety and Depression Scale, Body Uneasiness Test. At the T0 visit, a nurse selected patients and carried out a personalized educational intervention with the aims of adhering to drug therapies, monitoring blood pressure and dietary behavior (physical activity and water intake). At the T1 visit, patients performed psychological tests. At the T2 visit, the following evaluations were performed: a psychological interview together with the delivery and evaluation of the tests performed, an interview with the nurse to evaluate the adherence to the prescriptions, and a control of parameters such as physical activity, diet, water intake, drug therapy, and blood pressure. RESULTS: Therapeutic education can have a positive impact on patients’ health by improving adherence to the pharmacological therapy, diet and lifestyle. CONCLUSIONS: Therapeutic education improve the patient’s knowledge, treatments and correct behaviors as well as promotes an independent management of the disease. Through an educational intervention, the patient acquires the ability and the awareness to modify the wrong behaviors and to guarantee a balance between his needs and the pathology, thus improving the quality of life.

We present an efficient Cloud Computing (CC) implementation of the Parallel Small BAseline Subset (P-SBAS) algorithm, which is an advanced Differential Interferometric Synthetic Aperture Radar (DInSAR) technique for the generation of Earth surface displacement time series through distributed computing infrastructures. The rationale of our approach consists in properly distributing the large data volumes and the processing tasks involved in the P-SBAS chain among the available (virtual and/or physical) computing nodes of the CC infrastructure, so that each one of these elements can concurrently work on data that are physically stored on its own local volume. To do this, both an ad hoc management of the data flow and an appropriate scheduling of the parallel jobs have been also implemented to properly handle the high complexity of the P-SBAS workflow. The proposed solution allows minimizing the overall data transfer and network load, thus improving the P-SBAS efficiency and scalability within the exploited CC environments. The presented P-SBAS implementation has been extensively validated through two experimental analyses, which have been carried out by exploiting the Amazon Web Services (AWS) Elastic Cloud Compute (EC2) resources. The former analysis involves the processing of a large (128 SAR images) COSMO-SkyMed dataset, which has been performed by exploiting up to 64 computing nodes, and is aimed at demonstrating the P-SBAS scalable performances. The latter allows us to show the P-SBAS capability to generate DInSAR results at a regional scale (150 000 km2 in Southern California) in a very short time (about 9 h), by simultaneously processing 18 ENVISAT frames that correspond to a total of 741 SAR images, exploiting in parallel 144 AWS computing nodes. The presented results confirm the effectiveness of the proposed P-SBAS CC solution, which may contribute to further extend the frontiers of the DInSAR investigation at a very large scale.

Past genome-wide associate studies have identified hundreds of genetic loci that influence body size and shape when examined one trait at a time. Here, Jeff and colleagues develop an aggregate score of various body traits, and use meta-analysis to find new loci linked to body shape.

We present in this comment a Multi-Temporal SAR Interferometry (MT-InSAR) analysis showing that the results published by Milillo et al. (2019) in the Remote Sensing Journal, presenting the evidence of space geodetic observations relevant to displacements occurring before the collapse of the Morandi Bridge, happened in Genova (Italy) on the 14 August 2018, are questionable. In particular, we focus on the InSAR results obtained by Milillo et al. (2019) by processing the 3 m × 3 m resolution COSMO-SkyMed (CSK) data collected from ascending and descending orbits on the area of interest. These results, thanks to the high spatial resolution and the short revisit time characterizing this multi-orbit SAR dataset, represent the cornerstone of their analysis. The main findings of their study allow Milillo et al. to conclude that the InSAR processing of this COSMO-SkyMed dataset reveals the increased deformation magnitude over time of points located near the strands of the deck next to the collapsed pier, between 12 March 2017 and August 2018. In this comment, we show the results obtained by the IREA-CNR SAR team after processing the same ascending and descending CSK dataset, but by using two alternative and independent processing techniques: the Small BAseline Subset (SBAS) and the Advanced Tomographic SAR (TomoSAR) approaches, respectively. Our analysis shows that, although both the SBAS and the TomoSAR analyses allow achieving denser coherent pixel maps relevant to the Morandi bridge, nothing of the pre-collapse large displacements reported in Milillo et al. (2019) appears in our results, leading us to deeply disagree with the findings of their InSAR analysis.

We present in this work an advanced processing pipeline for continental scale differential synthetic aperture radar (DInSAR) deformation time series generation, which is based on the parallel small baseline subset (P-SBAS) approach and on the joint exploitation of Sentinel-1 (S-1) interferometric wide swath (IWS) SAR data, continuous global navigation satellite system (GNSS) position time-series, and cloud computing (CC) resources. We first briefly describe the basic rationale of the adopted P-SBAS processing approach, tailored to deal with S-1 IWS SAR data and to be implemented in a CC environment, highlighting the innovative solutions that have been introduced in the processing chain we present. They mainly consist in a series of procedures that properly exploit the available GNSS time series with the aim of identifying and filtering out possible residual atmospheric artifacts that may affect the DInSAR measurements. Moreover, significant efforts have been carried out to improve the P-SBAS processing pipeline automation and robustness, which represent crucial issues for interferometric continental scale analysis. Then, a massive experimental analysis is presented. In this case, we exploit: (i) the whole archive of S-1 IWS SAR images acquired over a large portion of Europe, from descending orbits, (ii) the continuous GNSS position time series provided by the Nevada Geodetic Laboratory at the University of Nevada, Reno, USA (UNR-NGL) available for the investigated area, and (iii) the ONDA platform, one of the Copernicus Data and Information Access Services (DIAS). The achieved results demonstrate the capability of the proposed solution to successfully retrieve the DInSAR time series relevant to such a huge area, opening new scenarios for the analysis and interpretation of these ground deformation measurements.

We present an automatic and unsupervised tool for the systematic generation of Sentinel-1 (S1) differential synthetic aperture radar interferometry (DInSAR) coseismic products. In particular, the tool first retrieves the location, depth, and magnitude of every seismic event from interoperable online earthquake catalogs (e.g., the United States Geological Survey (USGS) and the Italian National Institute of Geophysics and Volcanology (INGV) and then, for significant (with respect to a set of selected thresholds) earthquakes, it automatically triggers the downloading of S1 data and their interferometric processing over the area affected by the earthquake. The automatic system we developed has also been implemented within a Cloud-Computing (CC) environment, specifically the Amazon Web Services, with the aim of creating a global database of DInSAR S1 coseismic products, which consist of displacement maps and the associated wrapped interferograms and spatial coherences. This information will progressively be made freely available through the European Plate Observing System (EPOS) Research Infrastructure, thus providing the scientific community with a large catalog of DInSAR data that can be helpful for investigating the dynamics of surface deformation in the seismic zones around the Earth. The developed tool can also support national and local authorities during seismic crises by quickly providing information on the surface deformation induced by earthquakes.

CDK4/6 inhibitors (CDK4/6i) are recommended in patients with estrogen receptor (ER)-positive, HER2-negative advanced breast cancer (ABC). Up to now, no prognostic biomarkers have been identified in this setting. We retrospectively analyzed the expression of progesterone receptor (PR) and Ki67, assessed by immunohistochemistry, in 71 ABC patients treated with CDK4/6i and analyzed the impact of these markers on progression-free survival (PFS). The majority of patients 63/71 (88.7%) received palbociclib, 4 (5.6%) received ribociclib, and 4 (5.6%) received abemaciclib. A higher median value of Ki67 was observed in cases undergoing second-line treatment (p = 0.047), whereas the luminal B subtype was more prevalent (p = 0.005). In the univariate analysis of the first-line setting, luminal A subtype showed a trend towards a correlation with a longer PFS (p = 0.053). A higher continuous Ki67 value led to a significantly shorter PFS. When the interaction between pathological characteristics and line of treatment was considered, luminal B subtype showed a significantly (p = 0.043) worse outcome (Hazard Ratio (HR) 2.84; 1.03–7.82 95% Confidence Interval (CI)). PFS in patients undergoing endocrine therapy plus CDK4/6i was inversely correlated with Ki67 expression but not with PR, suggesting that tumor proliferation has a greater impact on cell cycle inhibitors combined with endocrine therapy than PR expression.

This paper reports that Bluetongue virus serotype 1 (BTV-1) infected blood collected during the 2006 Sardinia (Italy) epidemic from a ewe with clinical disease and stored at ~ 5°C for 10 years, caused Bluetongue (BT)-like clinical disease and death when inoculated into a susceptible Sarda breed ram. Anatomo-histopathological examination and Real-Time Reverse Transcriptase PCR (Real-Time RT-PCR) confirmed the presence of BTV-1 in several tissues proving that the BTV-1 2006 isolate has maintained its infectivity and virulence.

In this work, we investigate the Mw 5.9 earthquake occurred on 7 November 2019 in the East-Azerbaijan region, in northwestern Iran, which is inserted in the tectonic framework of the East-Azerbaijan Plateau, a complex mountain belt that contains internal major fold-and-thrust belts. We first analyze the Differential Synthetic Aperture Radar Interferometry (DInSAR) measurements obtained by processing the data collected by the Sentinel-1 constellation along ascending and descending orbits; then, we invert the achieved results through analytical modelling, in order to better constrain the geometry and characteristics of the seismogenic source. The retrieved fault model shows a rather shallow seismic structure, with a center depth at about 3 km, approximately NE–SW-striking and southeast-dipping, characterized by a left-lateral strike-slip fault mechanism (strike = 29.17°, dip = 79.29°, rake = −4.94°) and by a maximum slip of 0.80 m. By comparing the inferred fault with the already published geological structures, the retrieved solution reveals a minor fault not reported in the geological maps available in the open literature, whose kinematics is compatible with that of the surrounding structures, with the local and regional stress states and with the performed field observations. Moreover, by taking into account the surrounding geological structures reported in literature, we also use the retrieved fault model to calculate the Coulomb Failure Function at the nearby receiver faults. We show that this event may have encouraged, with a positive loading, the activation of the considered receiver faults. This is also confirmed by the distribution of the aftershocks that occurred near the considered surrounding structures. The analysis of the seismic events nucleated along the left-lateral strike-slip minor faults of the East-Azerbaijan Plateau, such as the one analyzed in this work, is essential to improve our knowledge on the seismic hazard estimation in northwestern Iran.