Search

Among the four endometrial cancer (EC) TCGA molecular groups, the MSI/hypermutated group represents an important percentage of tumors (30%), including different histotypes, and generally confers an intermediate prognosis for affected women, also providing new immunotherapeutic strategies. Immunohistochemistry for MMR proteins (MLH1, MSH2, MSH6 and PMS2) has become the optimal diagnostic MSI surrogate worldwide. This review aims to provide state-of-the-art knowledge on MMR deficiency/MSI in EC and to clarify the pathological assessment, interpretation pitfalls and reporting of MMR status. [ABSTRACT FROM AUTHOR]

In locally advanced cervical cancer (LACC), definitive chemo-radiotherapy is the standard treatment, but chemo-radiotherapy followed by surgery could be an alternative choice in selected patients. We enrolled 244 patients affected by LACC and treated with CT-RT followed by surgery in order to assess the prognostic role of the histological response using the Mandard scoring system. Results: A complete pathological response (TRG 0) was observed in 118 patients (48.4%), rare residual cancer cells (TRG2) were found in 49 cases (20.1%), increased number of cancer cells but fibrosis still predominating (TRG3) in 35 cases (14.3%), and 42 (17.2%) were classified as non-responders (TRG4–5). TRG was significantly associated with both OS (p < 0.001) and PFS (p < 0.001). The survival curves highlighted two main prognostic groups: TRG1-TRG2 and TRG3-TRG4–5. Main responders (TRG1–2) showed a 92% 5-year overall survival (5y-OS) and a 75% 5-year disease free survival (5y-DFS). Minor or no responders showed a 48% 5y-OS and a 39% 5y-DFS. The two-tiered TRG was independently associated with both DFS and OS in Cox regression analysis. Conclusion. We showed that Mandard TRG is an independent prognostic factor in post-CT/RT LACC, with potential benefits in defining post-treatment adjuvant therapy. [ABSTRACT FROM AUTHOR]

Simple Summary: The rate of positive parametrial lymph nodes in a series of apparent early-stage cervical cancer patients undergoing bilateral sentinel lymph node mapping was 3.1%. After ultrastaging of parametrial tissue, no occult micrometastasis was detected. Occult parametrial involvement in apparent early-stage cervical cancer might be overlooked with standard pathologic assessment. The primary endpoint of the present study was to assess the rate of positive parametrial lymph nodes and of microscopic continuous or discontinuous parametrial involvement. This is a retrospective, single-center, observational study including patients with FIGO 2018 stage IA1–IIA1 and IIIC1p in whom bilateral sentinel lymph node (SLN) detection and ultrastaging of SLN were performed according to institutional protocol, with surgery as primary treatment performed between May 2017 and February 2021, as well as type B2/C1/C2 (Querleu–Morrow) radical hysterectomy and usual histology (squamous cell, adenocarcinoma and adenosquamous carcinoma). Thirty-one patients were included in the study period. Six (18.7%) patients had metastatic lymph nodes, of whom four had only SLN metastasis (two cases of ITC, one case of micrometastasis and one case of macrometastasis). We found a macroscopic deposit of cancer cells in the parametrial lymph node of one patient (3.1%). There was a positive statistical correlation between the incidence of parametrial lymph node involvement and the metastatic pelvic lymph nodes (p = 0.038). When performed per patient, the sensitivity, negative predictive value and accuracy of parametrial lymph node involvement in predicting pelvic lymph node metastasis were 16.7%, 83.3% and 83.9%, respectively. Ultrastaging of parametrial tissue did not identify any occult continuous or discontinuous parametrial metastasis. In conclusion, the incidence of lymph node parametrial involvement in a retrospective series of early-stage cervical cancer was 3.1% of all included patients. Lymph node involvement of the parametrium was associated with lymph node metastasis. The sensitivity of parametrial lymph node involvement to predict pelvic lymph node metastasis was low. The lack of parametrial involvement revealed by parametrial ultrastaging could be related to the number of patients with tumors with a pathologic diameter < 2 cm (54.8%). Further prospective studies are needed to analyze the role of parametrial ultrastaging in early-stage cervical cancer and to assess whether it can be considered the "sentinel" of the sentinel lymph node. [ABSTRACT FROM AUTHOR]

Simple Summary: Ovarian hormones are involved in ovarian cancer pathogenesis. However, few reports have investigated the hormone receptor pattern according to BRCA mutational status. The aim of this single-center, observational, retrospective study was to explore the relationship between hormone receptor status and BRCA1/2 mutation in a cohort of 207 high-grade serous ovarian carcinoma (HGSOC) patients. Interesting differences emerged between BRCA-mutated and BRCA wild-type women, in terms of pattern of receptor expression and its association to the outcome. On the whole, our findings, though needing further validation, extend our understanding of the complex interplay between BRCA1/2 protein and hormone signaling, suggesting new pathways to be exploited in order to develop future personalized therapy. Several studies have explored the prognostic role of hormone receptor status in high-grade serous ovarian cancer (HGSOC) patients. However, few reports have investigated their expression according to BRCA mutational status. The aim of this single-center, observational, retrospective study was to explore the hormone receptor pattern and its potential prognostic role in a cohort of 207 HGSOC women stratified for BRCA mutational status. To this end, ERα, ERβ1, ERβ2, ERβ5, PR, and AR expression were assessed by immunohistochemistry in 135 BRCA-wild type (BRCA-wt) and 72 BRCA1/2 mutation carriers (BRCA-mut). No significant difference emerged in hormone receptor expression between the two sub-samples, except for a significantly lower ERα expression observed in pre-menopausal BRCA1/2-mut as compared to BRCA-wt patients (p = 0.02). None of the examined hormone receptors has revealed a significant prognostic role in the whole sample, apart from the ratio ERα/ERβ5 nuclear, for which higher values disclosed a positive role on the outcome in BRCA-wt subgroup (HR 0.77; CI 0.61–0.96; p = 0.019). Conversely, it negatively affected overall survival in the presence of BRCA1/2-mut (HR 1.41; CI 1.06–1.87; p = 0.020). Finally, higher PR levels were associated with platinum sensitivity in the whole sample (p = 0.019). Our data, though needing further validation, suggest a potential role of oestrogen-mediated pathways in BRCA1/2-associated HGSOC tumorigenesis, thus revealing a possible therapeutic potential for targeting this interaction. [ABSTRACT FROM AUTHOR]

The implementation of cancer molecular characterization in clinical practice has improved prognostic re-definition, extending the eligibility to a continuously increasing number of targeted treatments. Broad molecular profiling technologies better than organ-based approaches are believed to serve such dynamic purposes. We here present the workflow our institution adopted to run a comprehensive cancer genome profiling in clinical practice. This article describes the workflow designed to make a comprehensive cancer genome profiling program feasible and sustainable in a large-volume referral hospital. [ABSTRACT FROM AUTHOR]

Simple Summary: A more in-depth molecular characterization of uterine leiomyosarcomas (uLMS), a rare disease characterized with dismal prognosis, could provide data suitable for the identification of potential target-based drugs. We aimed to define frequencies of gene alterations in uLMS, especially regarding the somatic mutations of BRCA and HRR gene alterations, and identify the impact of these molecular alterations on clinical outcomes. This retrospective analysis of the mutational profile of uLMS showed that the most frequent alterations involved the TP53 gene, and that patients with TP53 alterations experienced a worse prognosis compared to patients with wild-type TP53 genes. Conversely, patient clinical outcomes were similar within patients with BRCA- and HRR-related genes versus non-HRR-related genes. However, although the frequency of patients with BRCA- and HRR-related alterations and mutations was relatively small, this setting could deserve an investigation into drug actionability, and potentially benefit from PARP inhibitors. Uterine leiomyosarcomas (uLMS) is a very rare disease, and patients experience a dismal prognosis even when treated with chemotherapy. Therefore, a more in-depth molecular characterization of this disease could provide suitable data for the identification of potential target-based drugs. This retrospective, single institutional study aimed to define the frequencies of gene alterations in uLMS, especially regarding the somatic mutations of BRCA and Homologous Recombination Repair (HRR) genes, and the impact of molecular alterations on clinical outcomes. The 16-genes Next-Generation Sequencing (NGS) panel, Homologous Recombination Solution TM (HRS, Sophia Genetics, Saint Sulpice, Switzerland), was used for the molecular evaluation of samples. The majority of patients (66/105, 63%) carried at least one sequence alteration, with a prevalence of TP53 involvement followed by RAD51B, BRCA1/2, and FANCL. Patients with TP53 gene alterations experienced a significantly worse prognosis for progression free survival (PFS) and overall survival (OS) versus wild-type patients. Given the number of patients with the BRCA1/2 mutation (N = 12), we included them in the HRR patient group; there was no difference in clinical outcomes with HRR versus non-HRR. The Cox's multivariate analysis showed that stage and TP53 gene alterations resulted in a significantly worse OS. The integration of gene networking data, such as tumor mutation burdens and cancer driver gene identification, could show a clearer discrimination of gene distribution patterns, and lead to the implementation of therapeutic targets. [ABSTRACT FROM AUTHOR]

We evaluate the combined usage of two systems, the Integral Quality Monitor (IQM) transmission detector and SoftDiso software, for in vivo dose monitoring by simultaneous detection of delivery and patient setup errors in whole breast irradiation. An Alderson RANDO phantom was adapted with silicon breast prostheses to mimic the female anatomy. Plans with simulated delivery errors were created from a reference left breast plan, and patient setup errors were simulated by moving the phantom. Deviations from reference values recorded by both monitoring systems were measured for all plans and phantom positions. A 2D global gamma analysis was performed in SoftDiso for all phantom displacements. Both IQM signals and SoftDiso R-values are sensitive to small MU variations. However, only IQM is sensitive to jaw position variations. Conversely, IQM is unable to detect patient positioning errors, and the R-value has good sensitivity to phantom displacements. A gamma comparison analysis allows one to determine alert thresholds to detect phantom shifts or relatively large rotations. The combined use of the IQM and SoftDiso allows for fast identification of both delivery and setup errors and substantially reduces the impact of error identification and correction on the treatment workflow. [ABSTRACT FROM AUTHOR]

Radar sensors have the potential to retrieve vertical forest structure measurements thanks to their capability to penetrate into the foliage. However, studies are needed in order to understand better the interaction of radar beamswith the canopy. Themost commonly used radar technique for estimating forest parameters operates fromspacecraft at differentwavelength (X-, C-, and L-band). In order to assist in the interpretation of satellite data for forest applications, and as a possible complementary technique to Lidar (Light detection and ranging), the Finnish Geospatial Research Institute has developed the first helicopter-borne profiling radar system operating in Ku-band, called Tomoradar, which is able to provide a vertical canopy profile. The study focuses on the analyses of Ku-band profiling radar waveforms and the backscatter signal of boreal forest, supported by simultaneously acquired Lidar measurements, in order to detect ground and canopy profiles and quantify the ground echo ratio under different canopy coverage and the backscatter signal variation through the vegetation. The Tomoradar data was acquired simultaneously with a lightweight Velodyne VLP-16 Lidar system in October 2016 over a boreal forest located in Evo in southern Finland. Additionally, highly accurate Riegl VQ-480 Lidar data, acquired in 2014, was used as a ground reference for both lightweight systems. We analysed the co- and cross-polarized (HH and HV) Tomoradar backscatter signals of a 600 m long profile. It is found that the Ku-band Tomoradar penetrates the canopy to a similar extent as the Velodyne Lidar, i.e., the distribution of backscatter signals through the vegetation follows the vegetation density. Moreover, the ground backscatter signal strength and ground echo ratio depend strongly on the presence of gaps in the canopy. By comparing the elevation of the corresponding canopy and ground Tomoradar signal peaks with the Velodyne Lidar data, the Tomoradar ground elevation accuracy is on average -0.03 m and -0.20 m for the cross- and co-polarization, respectively, whereas the bias of the canopy elevation is, on average, -0.58 m and 1.35 m for the cross- and co-polarization, respectively. With respect to the ground height data derived from the Lidar measurements of 2014, the Tomoradar ground profile reveals, on average, higher accuracy (i.e., 0.00 m (σ = 0.41 m) and 0.04 m (σ = 0.37 m) for the co-and cross-polarizations, respectively) than the Velodyne system (-0.37 m with σ = 0.25 m). [ABSTRACT FROM AUTHOR]

According to the Water Framework Directive, harbours that are classified as heavily modified water bodies must either reach or maintain good ecological potential. Moreover, following the marine spatial planning principles, the effects of port structure changes on water quality must also be considered. To support the sustainable management of harbour waters, we calculated flushing time (FT) through the use of a numerical model within the Civitavecchia port under different scenarios. To assess the effects of the realization of new infrastructure that will significantly alter the port configuration in the coming years, we also developed the flushing efficiency index (FEI). The increase in the harbour basin size due to the embankment extension result in high values of FT, particularly in the inner part of the port, in accordance with the highest values of the enrichment factor of the trace metals found in the sediment. The deterioration of water quality is confirmed by negative FEI values. Otherwise, the index assumes positive values after the realization of a second entrance in the southern part of Civitavecchia port, highlighting a drastic improvement in harbour water renewal. This study provides a low-cost and predictive tool to correctly address environmentally sustainable management of port activities. [ABSTRACT FROM AUTHOR]

The development of low-cost instrumentation plays a key role in marine environmental studies and represents one of the most innovative aspects of current oceanographic research. These kinds of devices can be used for several applications, ranging from vertical profilers to stand-alone systems, and can be installed on different platforms (buoys, Voluntary Observing Ships, underwater vehicles, etc.). The availability of low-cost technologies enables the realization of extended observatory networks for the study of marine physical and biological processes through an integrated approach merging in situ observations, forecasting models and remotely sensed data. We present new low-cost sensors and probes developed to measure marine temperature, conductivity, chlorophyll a and Chromophoric Dissolved Organic Matter fluorescence, focusing on sensing strategies, general architecture, laboratory trials, in situ tests and comparison with standard instruments. Furthermore, we report the expendable (New T-FLaP), vertical profiler (T-FLaPpro) and stand-alone (Spectra) applications of these technological developments that were tested during several oceanographic surveys in the Mediterranean Sea. [ABSTRACT FROM AUTHOR]

This methodology assesses the accuracy with which remote data characterizes a surface, as a function of Full Width at Half Maximum (FWHM). The purpose is to identify the best remote data that improves the characterization of a surface, evaluating the number of bands in the spectral range. The first step creates an accurate dataset of remote simulated data, using in situ hyperspectral reflectances. The second step evaluates the capability of remote simulated data to characterize this surface. The spectral similarity measurements, which are obtained using classifiers, provide this capability. The third step examines the precision of this capability. The assumption is that in situ hyperspectral reflectances are considered the "real" reflectances. They are resized with the same spectral range of the remote data. The spectral similarity measurements which are obtained from "real" resized reflectances, are considered "real" measurements. Therefore, the quantity and magnitude of "errors" (i.e., differences between spectral similarity measurements obtained from "real" resized reflectances and from remote data) provide the accuracy as a function of FWHM. This methodology was applied to evaluate the accuracy with which CHRIS-mode1, CHRIS-mode2, Landsat5-TM, MIVIS and PRISMA data characterize three coastal waters. Their mean values of uncertainty are 1.59%, 3.79%, 7.75%, 3.15% and 1.18%, respectively. [ABSTRACT FROM AUTHOR]

The spatial distribution of sea bed covers and seagrass in coastal waters is of key importance in monitoring and managing Mediterranean shallow water environments often subject to both increasing anthropogenic impacts and climate change effects. In this context we present a methodology for effective monitoring and mapping of Posidonia oceanica (PO) meadows in turbid waters using remote sensing techniques tested by means of LAI (Leaf Area Index) point sea truth measurements. Preliminary results using Daedalus airborne sensor are reported referring to the PO meadows at Civitavecchia site (central Tyrrhenian sea) where vessel traffic due to presence of important harbors and huge power plant represent strong impact factors. This coastal area, 100 km far from Rome (Central Italy), is characterized also by significant hydrodynamic variations and other anthropogenic factors that affect the health of seagrass meadows with frequent turbidity and suspended sediments in the water column. During 2011-2012 years point measurements of several parameters related to PO meadows phenology were acquired on various stations distributed along 20 km of coast between the Civitavecchia and S. Marinella sites. The Daedalus airborne sensor multispectral data were preprocessed with the support of satellite (MERIS) derived water quality parameters to obtain here improved thematic maps of the local PO distribution. Their thematic accuracy was then evaluated as agreement (R2) with the point sea truth measurements and regressive modeling using an on purpose developd method. [ABSTRACT FROM AUTHOR]

The aim of this study was to assess the relationship between endometrial metaplastic/reactive changes (EMRCs) and endometrial neoplastic lesions. Twenty cases of "simple" (without architecture complexity) EMRCs coexistent with endometrial malignant/premalignant lesions, twenty cases of neoplasia-unassociated EMRCs, and eight cases of complex metaplastic lesions were assessed by immunohistochemistry. EMRCs coexisted with endometrioid carcinoma (n = 12), atypical endometrial hyperplasia (n = 3), serous carcinoma (n = 2), and clear cell carcinoma (n = 3). Neoplasia-associated EMRCs showed a mean Ki67 labeling index of 12.6% (range 0–30%); with nuclear atypia in 16/20 (80%) cases; diffuse p16 expression in 15/20 (75%) cases; and heterogeneous ER, PR, and vimentin expression. Compared to the associated neoplasia, EMRCs showed a lower Ki67 expression (p < 0.001) and higher p16 expression (p < 0.001). No EMRC case showed mitotic activity, PTEN loss, MMR deficiency, nuclear β-catenin, p53-mutant pattern, Napsin A, or AMACR expression. No significant differences were found between neoplasia-associated and neoplasia-unassociated EMRCs. Complex metaplastic lesions showed a lower Ki67 expression than EMRCs (p = 0.044) and PTEN loss in 5/8 cases, even in the absence of nuclear atypia. In conclusion, neoplasia-associated simple EMRCs may show evident atypia and a worrisome immunophenotype, but no data support their involvement in endometrial carcinogenesis. Architectural complexity appears as a crucial factor to identify precancerous lesions. [ABSTRACT FROM AUTHOR]

This study reports the quantification and analysis of the ecosystem services (ESs) value of Posidonia oceanica (L.) Delile (1813) meadows in Italy (Liguria, Tuscany, Latium, Campania, Calabria, Apulia, Sardinia, and Sicily regions). The ES evaluation method of P. oceanica meadows applied in this study was obtained from a previous study in which the site-specific approach for the definition of the benefits and services was applied. The distribution of P. oceanica and the ESs economic value have been managed through an open-source geographic information system (QGIS), focusing on five essential ESs: carbon sequestration, bioremediation, oxygen production, erosion protection, and food production. The average value of the ESs obtained on the Italian national scale is €21,660.5 ha−1 yr−1, which is comparable with the values reported in the international literature concerning P. oceanica ESs. The results of this study confirm that the economic evaluation of ESs is an essential tool for the management of the coastal marine environment, especially considering the modularity of the applied approach. The value of the total benefits, considering the entire extension of the national P. oceanica meadows, represents significant value with respect to the Italian gross domestic product, and the individual budgets of the considered Italian regions. [ABSTRACT FROM AUTHOR]

Satellite-based long-term observations of vegetation cover development in combination with recent in-situ observations provide a basis to better understand the spatio-temporal changes of vegetation patterns, their sensitivity to climate drivers and thus climatic impact on proglacial landscape development. In this study we combined field investigations in the glacier forelands of Fürkele-, Zufall- and Langenferner (Ortles-Cevedale group/Eastern Italian Alps) with four different Vegetation Indices (VI) from Landsat scenes in order to test the suitability for modelling an area-wide vegetation cover map by using a Bayesian beta regression model (RStan). Since the model with the Normalized Difference Vegetation Index (NDVI) as predictor showed the best results, it was used to calculate a vegetation cover time series (1986–2019). The alteration of the proglacial areas since the end of the Little Ice Age (LIA) was analyzed from digital elevation models based on Airborne Laser Scanning (ALS) data and areal images, orthophotos, historical maps and field mapping campaigns. Our results show that a massive glacier retreat with an area loss of 8.1 km2 (56.9%; LIA–2019) resulted in a constant enlargement of the glacier forelands, which has a statistically significant impact on the degree of vegetation cover. The area covered by vegetation increased from 0.25 km2 (5.6%) in 1986 to 0.90 km2 (11.2%) in 2019 with a significant acceleration of the mean annual changing rate. As patterns of both densification processes and plant colonization at higher elevations can be reflected by the model results, we consider in-situ observations combined with NDVI time series to be powerful tools for monitoring vegetation cover changes in alpine proglacial areas. [ABSTRACT FROM AUTHOR]

Background. Extra-mammary Paget's disease (EMPD) is a rare neoplasm of epithelial origin, whose precise incidence is not clear. Starting from what is already known, we performed a systematic review and meta-analysis to investigate in male and female patients the immunohistochemical expression of biological markers that could serve as potential prognostic/therapeutic factors, including only human epidermal growth factor receptor 2 (HER2/neu), Estrogen Receptor (ER), Progesterone Receptor (PR), and Androgen Receptor (AR). Methods. A literature search was performed of the PubMed, Scopus, and Web of Science databases for English-language studies published from January 2000 to June 2020. Results. A total of 27 studies with 713 patients assessed the role of HER2/neu, AR, ER, and PR expression in male and female with EMPD. The overall rate of HER2/neu expression was 30%, the expression's rate for ER and AR was 13% and 40%, respectively, and the overall rate for PR was 8%. The subgroup analysis revealed that there is a different expression of molecular markers between male and female patients. Conclusions. This study revealed that AR status and HER2/neu overexpression/amplification have been shown as two fundamental pathogenetic pathways in both female and male patients affected by EMPD. [ABSTRACT FROM AUTHOR]

Since the end of the Little Ice Age (LIA), formerly glaciated areas have undergone considerable changes in their morphodynamics due to external forces and system-internal dynamics. Using multi-temporal high-resolution digital elevation models (DEMs) from different remote sensing techniques such as historical digital aerial images and light detection and ranging (LiDAR), and the resulting DEMs of difference (DoD), spatial erosion and accumulation patterns can be analyzed in proglacial areas over several decades. In this study, several morphological sediment budgets of different test sites on lateral moraines and different long-term periods were determined, covering a total period of 49 years. The test sites show high ongoing morphodynamics, and therefore low vegetation development. A decrease as well as an increase of the mean annual erosion volume could be demonstrated at the different test sites. All test sites show a slope–channel coupling and a decrease in the efficiency of sediment transport from slopes to channels. These developments are generally subject to conditions of increasing temperature, decreasing short-term precipitation patterns and increasing runoff from adjacent mountain streams. Finally, the study shows that sediment is still available on the investigated test sites and the paraglacial adjustment process is still in progress even after several decades of deglaciation (~133 years). [ABSTRACT FROM AUTHOR]

Svalbard archipelago is experiencing the effects of climate changes (i.e., glaciers' thickness reduction and glacier front retreat), but how ice melting affects water biogeochemistry is still unknown. Microbial communities often act as environmental sentinels, modulating their distribution and activity in response to environmental variability. To assess microbial response to climate warming, within the ARctic: present Climatic change and pAst extreme events (ARCA) project, a survey was carried out along a transect in Konsfjorden from off-shore stations towards the Kronebreen glacier. Total bacterial abundance and the fraction of actively respiring cells (labelled by cyanotetrazolium chloride, CTC), cultivable heterotrophic bacterial abundance, and extracellular enzymatic activities (leucine aminopeptidase (LAP), beta-glucosidase (GLU), and alkaline phosphatase (AP)) were measured. In addition, water temperature, salinity, dissolved oxygen, turbidity, total suspended matter (TSM), particulate and chromophoric dissolved organic matter (CDOM), chlorophyll-a (Chl-a), and inorganic compounds were determined, in order to evaluate whether variations in microbial abundance and metabolism were related with changes in environmental variables. Colder waters at surface (3.5–5 m) depths and increased turbidity, TSM, and inorganic compounds found at some hydrological stations close to the glacier were signals of ice melting. CDOM absorption slope values (275–295 nm) varied from 0.0077 to 0.0109 nm−1, and total bacterial cell count and cultivable heterotrophic bacterial abundance were in the order of 106 cells/mL and 103 colony forming units/mL, respectively. Enzymatic rates <1.78, 1.25, and 0.25 nmol/L/h were recorded for AP, LAP, and GLU, respectively. Inorganic compounds, TSM, and turbidity correlated inversely with temperature; AP was significantly related with CDOM absorption spectra and heterotrophic bacteria (r = 0.59, 0.71, p < 0.05); and LAP with Chl-a, Particulate Organic Carbon (POC) and Particulate Organic Nitrogen (PON) (0.97, 0.780, 0.734, p < 0.01), suggesting that fresh material from ice melting stimulated the metabolism of the cultivable fraction. [ABSTRACT FROM AUTHOR]

The response of very small glaciers to climate changes is highly scattered and little known in comparison with larger ice bodies. In particular, small avalanche-fed and debris-covered glaciers lack mass balance series of sufficient length. In this paper we present 13 years of high-resolution observations over the Occidentale del Montasio Glacier, collected using Airborne Laser Scanning, Terrestrial Laser Scanning, and Structure from Motion Multi-View Stereo techniques for monitoring its geodetic mass balance and surface dynamics. The results have been analyzed jointly with meteorological variables, and compared to a sample of "reference" glaciers for the European Alps. From 2006 to 2019 the mass balance showed high interannual variability and an average rate much closer to zero than the average of the Alpine reference glaciers (−0.09 vs. −1.42 m water equivalent per year, respectively). This behavior can be explained by the high correlation between annual balance and solid precipitation, which displayed recent peaks. The air temperature is not significantly correlated with the mass balance, which is main controlled by avalanche activity, shadowing and debris cover. However, its rapid increase is progressively reducing the fraction of solid precipitation, and increasing the length of the ablation season. [ABSTRACT FROM AUTHOR]

The Arctic region is greatly affected by climate change, with evident alterations in both physical and biological processes: temperatures are changing at a rate that is twice the global average and phytoplankton productivity is directly affected by ice melting. Continuous monitoring of this ecosystem is fundamental to gain greater understanding of the impact of changes on the natural environment, but the Global Ocean Observing System only provides partial coverage in these extreme areas, which are particularly difficult to reach. Technological progress in oceanographic measurement capabilities is indispensable for the implementation of marine observatories, especially in these remote regions. In recent years, autonomous systems and cost-effective technologies have proved to be valuable for increasing spatial and temporal coverage of data. This is the case with the innovative ArLoC (Arctic Low-Cost) probe, which was designed and developed for easy integration into various types of platforms, enabling continuous measurement of temperature, pressure and fluorescence of chlorophyll a. This work reports on the results of two scientific campaigns carried out in Kongsfjorden (Svalbard Islands) in 2018 in the framework of the UVASS (Unmanned Vehicles for Autonomous Sensing and Sampling) research project. The ArLoC probe was integrated onboard the PROTEUS (Portable RObotic TEchnology for Unmanned Surveys) unmanned semi-submersible vehicle and this allowed us to collect important data in the stretches of sea near tidewater glacier fronts. The acquired data showed several significant effects of glacier melting such as: high temperature and salinity gradients, which cause considerable variations in water mass stratification, and an increase in turbidity and the chlorophyll a concentration, which directly affects primary productivity and the trophic chain. During the surveys, ArLoC proved to be an easy-to-integrate, very reliable instrument, which permitted high spatial resolution investigation of ecological processes during glacier melting as never studied before. [ABSTRACT FROM AUTHOR]

Dissolved organic matter present in natural aquatic environments is a heterogeneous mixture of allochthonous and autochthonous materials. In coastal areas vulnerable to sewage waste, its biologically active component, the chromophoric dissolved organic matter (CDOM), is expected to change its composition and distribution in relation to anthropogenic activities, suggesting the possible use of CDOM as a proxy of fecal contamination. This study aimed at testing such hypothesis by investigating and relating the optical properties of CDOM with Escherichia coli abundance, physiological state, and enzymatic activities in a bathing area of the Northern Tyrrhenian Sea (Latium, Italy) affected by urban wastewaters. The parallel factor analysis (PARAFAC) applied to the excitation–emission matrices (EEMs) of CDOM allowed us to distinguish three main components: C1 (λEx/λEm = 342 nm/435 nm), C2 (λEx/λEm = 281–373 nm/460 nm), and C3 (λEx/λEm = 286 nm/360 nm). C1 and C2 corresponded to humic acids of terrestrial origin, while C3 to tryptophan, whose fluorescence peak was detected close to sewage sites, strongly related to active E. coli cells. The comparison between spectral and microbiological methods is suggested as a suitable approach to monitor bathing water quality for the implementation of coastal observing system capability. [ABSTRACT FROM AUTHOR]

Background. Gynecological neuroendocrine neoplasms (NENs) are extremely rare, accounting for 1.2–2.4% of the NENs. The aim of this study was to test cervical NENs for novel markers of potential utility for differential diagnosis and target therapy. Methods. All cases of our center (n = 16) were retrieved and tested by immunohistochemistry (IHC) for 12 markers including markers of neuroendocrine differentiation (chromogranin A, synaptophysin, CD56), transcription factors (CDX2 and TTF1), proteins p40, p63, p16INK4a, and p53, somatostatin receptors subtypes (SST2-SST5) and the proliferation marker Ki67 (MIB1). Results. All cases were poorly differentiated neuroendocrine carcinomas (NECs), 10 small cell types (small cell–neuroendocrine carcinomas, SCNECs) and 6 large cell types (large cell–neuroendocrine carcinomas, LCNECs); in 3 cases a predominant associated adenocarcinoma component was observed. Neuroendocrine cancer cells expressed at least 2 of the 3 tested neuroendocrine markers; p16 was intensely expressed in 14 (87.5%) cases; SST5 in 11 (56.25%, score 2–3, in 9 cases); SST2 in 8 (50%, score 2–3 in 8), CDX2 in 8 (50%), TTF1 in 5 (31.25%), and p53 in 1 case (0.06%). P63 and p40 expressions were negative, with the exception of one case that showed moderate expression for p63. Conclusions. P40 is a more useful marker for the differential diagnosis compared to squamous cell carcinoma. Neither CDX2 nor TTF1 expression may help the differential diagnosis versus potential cervical metastasis. P16 expression may suggest a cervical origin of NEC; however, it must be always integrated by clinical and instrumental data. The expression of SST2 and SST5 could support a role for SSAs (Somatostatin Analogues) in the diagnosis and therapy of patients with cervical NECs. [ABSTRACT FROM AUTHOR]

A catalyst-free heterocyclization reaction of α-chloroglycinates with thiobenzamides or thioureas leading to 2,4-disubstituted-5-acylamino-1,3-thiazoles has been developed. The methodology provides straightforward access to valuable building blocks for pharmaceutically relevant compounds. [ABSTRACT FROM AUTHOR]

The measurements of tree attributes required for forest monitoring and management planning, e.g., National Forest Inventories, are derived by rather time-consuming field measurements on sample plots, using calipers and measurement tapes. Therefore, forest managers and researchers are looking for alternative methods. Currently, terrestrial laser scanning (TLS) is the remote sensing method that provides the most accurate point clouds at the plot-level to derive these attributes from. However, the demand for even more efficient and effective solutions triggers further developments to lower the acquisition time, costs, and the expertise needed to acquire and process 3D point clouds, while maintaining the quality of extracted tree parameters. In this context, photogrammetry is considered a potential solution. Despite a variety of studies, much uncertainty still exists about the quality of photogrammetry-based methods for deriving plot-level forest attributes in natural forests. Therefore, the overall goal of this study is to evaluate the competitiveness of terrestrial photogrammetry based on structure from motion (SfM) and dense image matching for deriving tree positions, diameters at breast height (DBHs), and stem curves of forest plots by means of a consumer grade camera. We define an image capture method and we assess the accuracy of the photogrammetric results on four forest plots located in Austria and Slovakia, two in each country, selected to cover a wide range of conditions such as terrain slope, undergrowth vegetation, and tree density, age, and species. For each forest plot, the reference data of the forest parameters were obtained by conducting field surveys and TLS measurements almost simultaneously with the photogrammetric acquisitions. The TLS data were also used to estimate the accuracy of the photogrammetric ground height, which is a necessary product to derive DBHs and tree heights. For each plot, we automatically derived tree counts, tree positions, DBHs, and part of the stem curve from both TLS and SfM using a software developed at TU Wien (Forest Analysis and Inventory Tool, FAIT), and the results were compared. The images were oriented with errors of a few millimetres only, according to checkpoint residuals. The automatic tree detection rate for the SfM reconstruction ranges between 65% and 98%, where the missing trees have average DBHs of less than 12 cm. For each plot, the mean error of SfM and TLS DBH estimates is −1.13 cm and −0.77 cm with respect to the caliper measurements. The resulting stem curves show that the mean differences between SfM and TLS stem diameters is at maximum −2.45 cm up to 3 m above ground, which increases to almost +4 cm for higher elevations. This study shows that with the adopted image capture method, terrestrial SfM photogrammetry, is an accurate solution to support forest inventory for estimating the number of trees and their location, the DBHs and stem curve up to 3 m above ground. [ABSTRACT FROM AUTHOR]

Coupling between sea/land breeze and coastal circulation and the influence of wind-driven dynamics are substantially relevant for understanding coastal Mediterranean ecosystems. These coastal areas are particularly dynamic and are characterized by high-variable processes which drive biological phenomena at different time-scales. For the Tyrrhenian Sea, the available information on coastal dynamics is confined to large-scale general circulation with a focus exclusively on mesoscale pelagic dynamical processes. Hydrodynamic studies of Tyrrhenian coastal areas are very rare and focus on surface water circulation. For time scales that are associated with coastal water circulation, there is also limited knowledge on water column dynamics that are forced by local atmospheric circulations. This paper presents physical and biological data to document the effect of sea/land breeze circulation on ocean current dynamics and water column structures in a Northern Tyrrhenian coastal site. This coastal area is characterized by the presence of a relevant energy production site as well as one of the most important ports in the Mediterranean Sea for cruise traffic. Consequently, this coastal site is a transit point for many tourists and it is characterized by an increase of energy demand, especially during the summer season. The in-situ data show that coastal currents are predominantly controlled by the tide and local wind and respond rapidly to changes in wind direction. Water column thermal structure analyses reveal significant changes with the morning's rotation of breeze: lifting of isotherms (cooling) was typically observed in deep layers during early mornings, accompanied by fluctuations in isotherms. The performed investigations provide valuable inputs for coastal ecosystem modeling and for a better understanding of the coastal processes that are significant for environmental and navigational interests. [ABSTRACT FROM AUTHOR]

This work focuses on the accuracy estimation of canopy height models (CHMs) derived from image matching of Pléiades stereo imagery over forested mountain areas. To determine the height above ground and hence canopy height in forest areas, we use normalised digital surface models (nDSMs), computed as the differences between external high-resolution digital terrain models (DTMs) and digital surface models (DSMs) from Pléiades image matching. With the overall goal of testing the operational feasibility of Pléiades images for forest monitoring over mountain areas, two questions guide this work whose answers can help in identifying the optimal acquisition planning to derive CHMs. Specifically, we want to assess (1) the benefit of using tri-stereo images instead of stereo pairs, and (2) the impact of different viewing angles and topography. To answer the first question, we acquired new Pléiades data over a study site in Canton Ticino (Switzerland), and we compare the accuracies of CHMs from Pléiades tri-stereo and from each stereo pair combination. We perform the investigation on different viewing angles over a study area near Ljubljana (Slovenia), where three stereo pairs were acquired at one-day offsets. We focus the analyses on open stable and on tree covered areas. To evaluate the accuracy of Pléiades CHMs, we use CHMs from aerial image matching and airborne laser scanning as reference for the Ticino and Ljubljana study areas, respectively. For the two study areas, the statistics of the nDSMs in stable areas show median values close to the expected value of zero. The smallest standard deviation based on the median of absolute differences (σMAD) was 0.80 m for the forward-backward image pair in Ticino and 0.29 m in Ljubljana for the stereo images with the smallest absolute across-track angle (−5.3°). The differences between the highest accuracy Pléiades CHMs and their reference CHMs show a median of 0.02 m in Ticino with a σMAD of 1.90 m and in Ljubljana a median of 0.32 m with a σMAD of 3.79 m. The discrepancies between these results are most likely attributed to differences in forest structure, particularly tree height, density, and forest gaps. Furthermore, it should be taken into account that temporal vegetational changes between the Pléiades and reference data acquisitions introduce additional, spurious CHM differences. Overall, for narrow forward–backward angle of convergence (12°) and based on the used software and workflow to generate the nDSMs from Pléiades images, the results show that the differences between tri-stereo and stereo matching are rather small in terms of accuracy and completeness of the CHM/nDSMs. Therefore, a small angle of convergence does not constitute a major limiting factor. More relevant is the impact of a large across-track angle (19°), which considerably reduces the quality of Pléiades CHMs/nDSMs. [ABSTRACT FROM AUTHOR]

The Arctic region is known to be severely affected by climate change, with evident alterations in both physical and biological processes. Monitoring the Arctic Ocean ecosystem is key to understanding the impact of natural and human-induced change on the environment. Large data sets are required to monitor the Arctic marine ecosystem and validate high-resolution satellite observations (e.g., Sentinel), which are necessary to feed climatic and biogeochemical forecasting models. However, the Global Observing System needs to complete its geographic coverage, particularly for the harsh, extreme environment of the Arctic Region. In this scenario, autonomous systems are proving to be valuable tools for increasing the resolution of existing data. To this end, a low-cost, miniaturized and flexible probe, ArLoC (Arctic Low-Cost probe), was designed, built and installed on an innovative unmanned marine vehicle, the PROTEUS (Portable RObotic TEchnology for Unmanned Surveys), during a preliminary scientific campaign in the Svalbard Archipelago within the UVASS project. This study outlines the instrumentation used and its design features, its preliminary integration on PROTEUS and its test results. [ABSTRACT FROM AUTHOR]

Standard chlorophyll-a (chl-a) algorithms, which rely on Moderate Resolution Imaging Spectro-radiometer (MODIS) data aboard the Aqua satellite, usually show different performances depending on the area under consideration. In this paper, we assessed their accuracy in retrieving the chl-a concentration in the Basilicata Ionian Coastal waters (Ionian Sea, South of Italy). The outputs of one empirical (Med-OC3) and two semi-analytical algorithms, the Garver–Siegel–Maritorena (GSM) and the Generalized Inherent Optical Properties (GIOP) model, have been compared with ground measurements acquired during three different measurement campaigns. The achieved results prove the poor accuracy (adjusted R2 value of 0.12) of the investigated empirical algorithm and, conversely, the good performance of semi-analytical algorithms (adjusted R2 ranging from 0.74 to 0.79). The co-existence of Coloured Dissolved Organic Matter (CDOM) and Non-Algal Particles (NAP) has likely determined large errors in the reflectance ratios used in the OCx form algorithms. Finally, a local scale assessment of the bio-optical properties, on the basis of the in situ dataset, allowed for the definition of an operational local scale-tuned version of the MODIS chl-a algorithm, which assured increased accuracy (adjusted R2 value of 0.86). Such a tuned algorithm version can provide useful information which can be used by local authorities within regional management systems. [ABSTRACT FROM AUTHOR]

The Gulf of Gaeta, in the western margin of central Italy, is characterized by a coastal morphology that creates a natural sheltered area in which fine sediment settles. The new port regulatory plan provides for dock expansions and dredging works that could alter the suspended particulate matter (SPM) concentration. The present study investigates the dynamics of the Gulf of Gaeta with a focus on the dynamic processes that affect the fine particle concentration. The study was conducted through a multidisciplinary approach that involves remote sensing acquisitions (satellite imagery and X-band radar), measurements in situ (water sampling, wave buoy, weather station, turbidity station, CTD profiles), and numerical modelling (SWAN and Delft3D FLOW). The X-band radar system supports the analysis of the dynamic processes of the SPM concentration providing a large dataset useful for the hydrodynamic model’s validation. The analysis reveals a strong influence of nearby rivers in modulating the SPM at the regional scale. Short-term high and low fluctuations in SPM concentration within the gulf are triggered by the local effect of the main physical forces. In particular, the direction of events and bottom sediment resuspension play a key role in modulating the SPM concentration while micro-tidal regime does not appear to influence turbidity in the study area. This approach represents an important tool in improving the long-term coastal management strategy from the perspective of sustainable human activities in marine coastal ecosystems. [ABSTRACT FROM AUTHOR]

Background: Several pathological parameters, including tumor size, depth of stromal invasion, lympho-vascular space invasion and lymph node status, have been proposed as prognostic predictors in cervical cancer. However, given the high mortality and recurrence rate of cervical cancer, novel parameters that are able to provide additional prognostic information are needed in order to allow a better prognostic stratification of cervical cancer patients., Methods: A search was conducted on PubMed to identify relevant literature data regarding prognostic factors in cervical cancer. The key words "cervical cancer", "prognostic factors", "pathology", and "outcome" were used., Results: The novel pathological grading system based on tumor budding and cell nest size appeared the most relevant prognostic factor in primary neoplasms. Moreover, other potentially useful prognostic factors were tumor size, depth of stromal invasion, lympho-vascular space invasion, perineural invasion, tumor-free distance and tumor-infiltrating lymphocytes. Prognostic factors related to advanced-stage cervical cancer, including lymph-nodes status, endometrial and cervical involvement as well as distant metastases, were also taken into consideration., Conclusions: According to our findings, tumor budding and cell nest size grading system, depth of stromal invasion, lympho-vascular space invasion, perineural invasion, tumor-free distance and tumor-infiltrating lymphocytes appeared the most relevant factors included in the pathology report.

BRCA 1/2 genes mutation status can already determine the therapeutic algorithm of high grade serous ovarian cancer patients. Nevertheless, its assessment is not sufficient to identify all patients with genomic instability, since BRCA 1/2 mutations are only the most well-known mechanisms of homologous recombination deficiency (HR-d) pathway, and patients displaying HR-d behave similarly to BRCA mutated patients. HRd assessment can be challenging and is progressively overcoming BRCA testing not only for prognostic information but more importantly for drugs prescriptions. However, HR testing is not already integrated in clinical practice, it is quite expensive and it is not refundable in many countries. Selecting patients who are more likely to benefit from this assessment (BRCA 1/2 WT patients) at an early stage of the diagnostic process, would allow an optimization of genomic profiling resources. In this study, we sought to explore whether somatic BRCA1/2 genes status can be predicted using computational pathology from standard hematoxylin and eosin histology. In detail, we adopted a publicly available, deep-learning-based weakly supervised method that uses attention-based learning to automatically identify sub regions of high diagnostic value to accurately classify the whole slide (CLAM). The same model was also tested for progression free survival (PFS) prediction. The model was tested on a cohort of 664 (training set: n = 464, testing set: n = 132) ovarian cancer patients, of whom 233 (35.1%) had a somatic BRCA 1/2 mutation. An area under the curve of 0.7 and 0.55 was achieved in the training and testing set respectively. The model was then further refined by manually identifying areas of interest in half of the cases. 198 images were used for training (126/72) and 87 images for validation (55/32). The model reached a zero classification error on the training set, but the performance was 0.59 in terms of validation ROC AUC, with a 0.57 validation accuracy. Finally, when applied to predict PFS, the model achieved an AUC of 0.71, with a negative predictive value of 0.69, and a positive predictive value of 0.75. Based on these analyses, we have planned further steps of development such as proving a reference classification performance, exploring the hyperparameters space for training optimization, eventually tweaking the learning algorithms and the neural networks architecture for better suiting this specific task. These actions may allow the model to improve performances for all the considered outcomes.

In endometrial carcinoma, both L1CAM overexpression and microcystic, elongated and fragmented (MELF) patterns of invasion have been related to epithelial-to-mesenchymal transition and metastatic spread. We aimed to assess the association between L1CAM expression, the MELF pattern, and lymph node status in endometrial carcinoma. Consecutive cases of endometrial carcinoma with MELF pattern were immunohistochemically assessed for L1CAM. Inclusion criteria were endometrioid-type, low-grade, stage T1, and known lymph node status. Uni- and multivariate logistic regression were used to assess the association of L1CAM expression with lymph node status. Fifty-eight cases were included. Most cases showed deep myometrial invasion (n = 42, 72.4%) and substantial lymphovascular space invasion (n = 34, 58.6%). All cases were p53-wild-type; 17 (29.3%) were mismatch repair-deficient. Twenty cases (34.5%) had positive nodes. No cases showed L1CAM positivity in ≥10% of the whole tumor. MELF glands expressed L1CAM at least focally in 38 cases (65.5%). L1CAM positivity in ≥10% of the MELF component was found in 24 cases (41.4%) and was the only significant predictor of lymph node involvement in both univariate (p < 0.001) and multivariate analysis (p < 0.001). In conclusion, L1CAM might be involved in the development of the MELF pattern. In uterine-confined, low-grade endometrioid carcinomas, L1CAM overexpression in MELF glands may predict lymph node involvement.

Introduction: The study's aim was to investigate the immunohistochemical (IHC) expression of biological markers as potential prognostic/therapeutic factors in vulvar squamous cell carcinoma (VSCC)., Methodology: A series of 101 patients surgically treated at our center from 2016 to 2020 were retrospectively enrolled: 53 node-negative (Group A) and 48 node-positive (Group B). A total of 146 samples, 101 from primary tumor (T) and 45 from nodal metastases (N), were investigated. The IHC panel included: p16, p53, MLH1, MSH2, MSH6, PMS2, PD-L1, CD3, HER2/neu, ER, PR, EGFR, VEGF, and CD31. The reactions were evaluated on qualitative and semi-quantitative scales. Generalized Linear Model (GLM) and cluster analysis were performed in R statistical environment. A distance plot compared the IHC panel of T with the correspondent N., Results: In Group A: p16-positive expression (surrogate of HPV-dependent pathway) was significantly higher (20.8% vs. 6.2%, p = 0.04). In Group B: PD-L1 positivity and high EGFR expression were found, respectively, in 77.1% and 97.9% patients (T and/or N). Overall, p16-negative tumors showed a higher PD-L1 expression (60.9% vs. 50.0%). In both groups: tumoral immune infiltration (CD3 expression) was mainly moderate/intense (80% vs. 95%); VEGF showed strong/moderate-diffuse expression in 13.9% of T samples; CD31, related to tumoral microvessel density (MVD), showed no difference between groups; a mutated p53 and over-expressed PD-L1 showed significant association with nodal metastasis, with Odds Ratios (OR) of 4.26 (CI 95% = 1.14-15.87, p = 0.03) and 2.68 (CI 95% = 1.0-7.19, p < 0.05), respectively; since all mismatch repair proteins (MMR) showed a retained expression and ER, PR, and HER2/neu were negative, they were excluded from further analysis. The cluster analysis identified three and four sub-groups of molecular profiles, respectively, in Group A and B, with no difference in prognosis. The molecular signature of each N and corresponding T diverged significantly in 18/41 (43.9%) cases., Conclusions: Our results support a potential role of immune checkpoint inhibitors and anti-VEGF and anti-EGFR drugs especially in patients with worse prognosis (metastatic, HPV-independent). A panel including EGFR, VEGF, PDL1, p16, and p53 might be performed routinely in primary tumor and repeated in case of lymph node metastases to identify changes in marker expression.

Background: Ovarian cancer (OC) has recently attracted attention for the use of PD-1/PD-L1 axis blocking agents, with durable activity reported only in a subset of patients. The most used biomarker for sensitivity to the PD-1/PD-L1 axis blockade is tumour PD-L1 status by immunohistochemistry. However, patient stratification using this method suffers from intrinsic heterogeneity of OC, likely contributing to the unsatisfactory results obtained so far. Cells communicate with each other by releasing microvesicles (MVs) that carry parental cell surface features. Thus, we hypothesised that PD-L1 + tumour cells (TC) and infiltrating PD-L1 + leukocytes should shed MVs carrying surface PD-L1 that may serve as a proxy for the whole tumour PD-L1 status., Results: We showed for the first time the presence of measurable amounts of TC- and leukocyte-derived PD-L1 + MVs (range: 1.4-178.8 MVs/μL and 6.2-504.8 MVs/μL, respectively) in the plasma of high-grade serous OC (HGSOC) patients ( n = 63), using a sensitive flow cytometry platform. The concentration of PD-L1 + MVs of either origin did not associate with the PD-L1 status of TCs and leukocytes in the tumour biopsies, suggesting that the circulating PD-L1 + MVs also included ones from locations not selected for immunohistochemistry analysis and represented the PD-L1 status of the whole tumour mass. In this study, we also describe the serendipitous discovery of circulating PD-L1 + MVs of platelet origin (10.3-2409.6 MVs/μL)., Conclusions: The enumeration of circulating PD-L1 + MVs in HGSOC patients may provide a novel direction for assessing the tumour PD-L1 status and contribute to HGSOC patient stratification for immunotherapy interventions. The presence of circulating PD-L1 + MVs of platelet origin, a finding not yet reported in HGSOC patients, warrants further studies.