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BACKGROUND: The prognostic role of programmed death-ligand 1 (PD-L1) expression in patients with localised and locally advanced non-small cell lung cancer has not been fully elucidated. This information could help to better interpret recent and upcoming results of phase III adjuvant or neoadjuvant anti-PD-1/PD-L1 immunotherapy studies. METHODS: In a cohort of 146 patients with early or locally advanced non-small cell lung cancer treated with curative intent (by surgery or radiotherapy), we investigated the prognostic value of PD-L1 expression and its correlation with other biological and clinical features. PD-L1 expression was stratified by quartiles. Primary endpoints were overall and disease-free survival. We also analysed the prognostic impact of the presence of actionable mutations, implemented treatment modality and completion of the treatment plan. Neither type of patient received neoadjuvant or adjuvant immunotherapy or target therapy. RESULTS: Of the 146 selected patients, 32 (21.9%) presented disease progression and 15 died (10.3%) at a median follow-up of 20 months. In a univariable analysis, PD-L1 expression ≥25% was associated with significantly lower disease-free survival (hazard ratio [HR]) 1.9, 95% confidence interval [CI] 1.0–3.9, p= 0.049). PD-L1 expression ≥50% did not lead to disease-free survival or overall survival benefits (HR 1.2 and 1.1, respectively; 95% CI 0.6–2.6 and 0.3–3.4, respectively; pnot significant). In a multivariate analysis, a stage >I (HR 2.7, 95% CI 1.2–6, p = 0.012) and having an inoperable tumour (HR 3.2, 95% CI 1.4–7.4, p = 0.005) were associated with lower disease-free survival. CONCLUSION: The population of patients with early-stage non-small cell lung cancer and PD-L1 expression ≥25% who were treated with curative intent during the pre-immunotherapy era exhibited a worse prognosis. This finding provides justification for the utilisation of adjuvant immunotherapy in this subgroup of patients, based on the current evidence derived from disease-free survival outcomes. However, for patients with PD-L1 expression

Abstract Interplanetary space travel poses many hazards to the human body. To protect astronaut health and performance on critical missions, there is first a need to understand the effects of deep space hazards, including ionizing radiation, confinement, and altered gravity. Previous studies of rodents exposed to a single such stressor document significant deficits, but our study is the first to investigate possible cumulative and synergistic impacts of simultaneous ionizing radiation, confinement, and altered gravity on behavior and cognition. Our cohort was divided between 6-month-old female and male mice in group, social isolation, or hindlimb unloading housing, exposed to 0 or 50 cGy of 5 ion simplified simulated galactic cosmic radiation (GCRsim). We report interactions and independent effects of GCRsim exposure and housing conditions on behavioral and cognitive performance. Exposure to GCRsim drove changes in immune cell populations in peripheral blood collected early after irradiation, while housing conditions drove changes in blood collected at a later point. Female mice were largely resilient to deficits observed in male mice. Finally, we used principal component analysis to represent total deficits as principal component scores, which were predicted by general linear models using GCR exposure, housing condition, and early blood biomarkers.

Augmented/virtual realities (ARs/VRs) promise to revolutionize STEM education. However, most easy-to-use tools are limited to static visualizations, which limits the approachable content, whereas more interactive and dynamic alternatives require costly hardware, preventing large-scale use and evaluation of pedagogical effects. Here, we introduce https://MoleculARweb.epfl.ch, a free, open-source web site with interactive AR webpage-based apps that work out-of-the-box in laptops, tablets, and smartphones, where students and teachers can naturally handle virtual objects to explore molecular structure, reactivity, dynamics, and interactions, covering topics from inorganic, organic, and biological chemistry. With these web apps, teachers and science communicators can develop interactive material for their lessons and hands-on activities for their students and target public, in person or online, as we exemplify. Thousands of accesses to moleculARweb attest to the ease of use; teacher feedback attests to the utility in online teaching and homework during a pandemic; and in-class plus online surveys show that users find AR engaging and useful for teaching and learning chemistry. These observations support the potential of AR in future education and show the large impact that modern web technologies have in democratizing access to digital learning tools, providing the possibility to mass-test the pedagogical effect of these technologies in STEM education.

This study uses satellite radar observations to investigate the triggering and recovery mechanisms of landslides that are accelerated by earthquakes without immediate failures but showing a prolonged response.

Abstract Background The cysts of the male pelvic floor represent a rare clinical entity. Their origin is linked to an altered development of paramesonephric and mesonephric ducts during embryogenesis. Case presentation We report our experience regarding two patients presenting cysts of the ejaculatory system treated with open and mini-invasive surgery. The patients referred to our clinic with nonspecific symptoms and the diagnosis was obtained by radiological investigations. The patient treated with an open approach developed a pelvic purulent collection and a fistula of the prostatic urethra, managed with surgical drainage and prolonged bladder catheterization. On the other hand, the patient treated with laparoscopic approach did not develop any complications. No sexual or ejaculatory disorders were reported. Conclusions Patients with congenital cysts of the pelvic floor must be adequately informed about the risks and benefits of surgery and a careful counseling is mandatory before surgery. Treatment is recommended for symptomatic patients and an endoscopic approach is associated with a high rate of recurrence. A laparoscopic approach, when possible, is desirable.

In this study, the extraction kinetics of pink pepper (Schinus terebinthifolius Raddi) using supercritical CO2 were investigated. S. terebinthifolius is an important fruit tree that is native to Brazil. Owing to its medicinal properties, this plant demonstrates potential for commercial use. However, to date, the extraction of compounds from pink pepper using SFE has been investigated in few studies, and no reports have been found on kinetic models for the SFE of compounds from this raw material. A design of experiments was developed to evaluate the influences of temperature and pressure on the extraction kinetics. The models of Tan and Liou, Crank, Esquível et al., and Martínez et al. were fitted to the extraction curves, and compared to models by artificial neural networks (ANNs). The influences of three databases and input neurons on modeling by a feedforward ANN with three layers were investigated. The pressure effect is pronounced, consequently increasing the extraction yield by increasing the solvent density. Temperature exhibits a complex effect on both solvent density and solute vapor pressure. The curves are governed mainly by periods of falling extraction and diffusion-controlled rates. The ANN, Esquível et al., and Crank models yield the most suitable results. However, the ANN model exhibits better predictability than that of the other models.

Introduction: Superficial folliculitis of the scalp (SFS) is a common complaint in clinical practice, and initial presentation may be difficult to differentiate as they may appear very similar to each other. Objectives: The aim of this thesis is to describe the pathologies that occur clinically as folliculitis of the scalp, identify their causes and characteristics and create a standardized classification. Methods: This is a retrospective clinical, dermoscopic and histopathological study over 10 years of dermatologic consultations. Only individuals with a confirmed diagnosis of SFS (updated diagnostic criteria or biopsy) were included. Results: In this review, we describe the various clinical features of different causes of SFS in ninety-nine cases and divided into infectious due to fungus, bacteria, or virus and inflammatory conditions such as rosacea, acneiform eruption and Ofuji syndrome. Conclusions: The clinician must differentiate SFS from other underlying scarring disorders to prevent poorer outcomes. We created an algorithm to help the clinician reach a proper diagnosis.

ObjectiveWe aimed to report on previously unappreciated clinical features associated with FOXP1-related intellectual disability (ID) syndrome, a rare neurodevelopmental disorder characterized by global developmental delay, intellectual disability, and language delay, with or without autistic features.MethodsWe performed whole-exome sequencing (WES) to molecularly characterize an individual presenting with ID, epilepsy, autism spectrum disorder, behavioral problems, and facial dysmorphisms as major features.ResultsWES allowed us to identify a previously unreported de novo splice site variant, c.1429-1G>T (NM_032682.6), in the FOXP1 gene (OMIM*605515) as the causative event underlying the phenotype. Clinical reassessment of the patient and revision of the literature allowed us to refine the phenotype associated with FOXP1 haploinsufficiency, including hyperkinetic movement disorder and flat angiomas as associated features. Interestingly, the patient also has an asymmetric face and choanal atresia and a novel de novo variant of the CHD7 gene.ConclusionWe suggest that FOXP1-related ID syndrome may also predispose to the development of hyperkinetic movement disorders and flat angiomas. These features could therefore require specific management of this condition.

Glioblastoma multiforme (GBM) is usually treated with surgery followed by adjuvant partial radiotherapy combined with temozolomide (TMZ) chemotherapy. Recent studies demonstrated a better survival and good response to TMZ in methylguanine-DNA methyltransferase (MGMT)-methylated GBM cases. However, approximately 20% of patients with MGMT-unmethylated GBM display an unexpectedly favorable outcome. Therefore, additional mechanisms related to the TMZ response need to be investigated. As such, we decided to investigate the clinical relevance of six miRNAs involved in brain tumorigenesis (miR-181c, miR-181d, miR-21, miR-195, miR-196b, miR-648) as additional markers of response and survival in patients receiving TMZ for GBM. We evaluated miRNA expression and the interplay between miRNAs in 112 IDH wt GBMs by applying commercial assays. Then, we correlated the miRNA expression with patients’ clinical outcomes. Upon bivariate analyses, we found a significant association between the expression levels of the miRNAs analyzed, but, more interestingly, the OS curves show that the combination of low miR-648 and miR-181c or miR-181d expressions is associated with a worse prognosis than cases with other low-expression miRNA pairs. To conclude, we found how specific miRNA pairs can influence survival in GBM cases treated with TMZ.

The genetic causes of epilepsies and developmental and epileptic encephalopathies (DEE) with onset in early childhood are increasingly recognized. Their outcomes vary from benign to severe disability. In this paper, we wished to retrospectively review the clinical, genetic, EEG, neuroimaging, and outcome data of patients experiencing the onset of epilepsy in the first three years of life, diagnosed and followed up in four Italian epilepsy centres (Epilepsy Centre of San Paolo University Hospital in Milan, Child Neurology and Psychiatry Unit of AUSL-IRCCS di Reggio Emilia, Pediatric Neurology Unit of Vittore Buzzi Children’s Hospital, Milan, and Child Neurology and Psychiatry Unit, IRCCS Mondino Foundation, Pavia). We included 168 patients (104 with monogenic conditions, 45 with copy number variations (CNVs) or chromosomal abnormalities, and 19 with variants of unknown significance), who had been followed up for a mean of 14.75 years. We found a high occurrence of generalized seizures at onset, drug resistance, abnormal neurological examination, global developmental delay and intellectual disability, and behavioural and psychiatric comorbidities. We also documented differing presentations between monogenic issues versus CNVs and chromosomal conditions, as well as atypical/rare phenotypes. Genetic early-childhood-onset epilepsies and DEE show a very wide phenotypic and genotypic spectrum, with a high risk of complex neurological and neuropsychiatric phenotypes.

Abstract Leucine-rich repeat kinase 2 (LRRK2) is a kinase involved in different cellular functions, including autophagy, endolysosomal pathways, and immune function. Mutations in LRRK2 cause autosomal-dominant forms of Parkinson’s disease (PD). Heterozygous mutations in GBA1, the gene encoding the lysosomal enzyme glucocerebrosidase (GCase), are the most common genetic risk factors for PD. Moreover, GCase function is altered in idiopathic PD and in other genetic forms of the disease. Recent work suggests that LRRK2 kinase activity can regulate GCase function. However, both a positive and a negative correlation have been described. To gain insights into the impact of LRRK2 on GCase, we performed a comprehensive analysis of GCase levels and activity in complementary LRRK2 models, including (i) LRRK2 G2019S knock in (GSKI) mice, (ii) peripheral blood mononuclear cell (PBMCs), plasma, and fibroblasts from PD patients carrying LRRK2 G2019S mutation, (iii) patient iPSCs-derived neurons; (iv) endogenous and overexpressed cell models. In some of these models we found a positive correlation between the activities of LRRK2 and GCase, which was further confirmed in cell lines with genetic and pharmacological manipulation of LRRK2 kinase activity. GCase protein level is reduced in GSKI brain tissues and in G2019S iPSCs-derived neurons, but increased in fibroblasts and PBMCs from patients, suggesting cell-type-specific effects. Overall, our study indicates that LRRK2 kinase activity affects both the levels and the catalytic activity of GCase in a cell-type-specific manner, with important implications in the context of therapeutic application of LRRK2 inhibitors in GBA1-linked and idiopathic PD.

We present a new activity on the moleculARweb platform on molecular symmetry elements, two more languages, a new marker-less augmented reality mode, and a new virtual reality tool for VR headsets.

Abstract Autonomous Reef Monitoring Structures (ARMS) are artificial mini‐reefs designed for standardized sampling of sessile and small motile cryptobenthic organisms. ARMS are also effective for collecting small cryptobenthic fishes, such as the combtooth blennies of the genus Cirripectes. Recent studies discovered several Cirripectes species endemic to islands or archipelagos, in spite of the generally broad distributions of tropical and subtropical blennies. Thus, to evaluate the diversity and distribution of Cirripectes species in the Mascarene Archipelago, a little‐studied region but an important biodiversity hotspot, complete mitochondrial genomes, and nuclear rhodopsin genes were sequenced for 39 specimens collected with ARMS deployed on outer reef slopes at Reunion and Rodrigues islands. Mitochondrial COI sequences were analyzed to integrate these specimens within the largest dataset of publicly available sequences. Three species were found in the Mascarene Archipelago, Cirripectes castaneus, Cirripectes randalli, and Cirripectes stigmaticus. C. castaneus and C. stigmaticus both have an Indo‐Pacific distribution with several haplotypes shared among distant localities. In agreement with the literature, C. randalli shows a small‐range endemism restricted to the Mascarenes. We confirmed the presence of C. castaneus, C. randalli, and C. stigmaticus in Rodrigues, and the presence of C. stigmaticus in Reunion. This study contributes to filling the gaps in taxonomic and molecular knowledge of the reef cryptobiome in the South‐West Indian Ocean, and provides the first complete mitogenomes for the genus, a crucial step for future molecular‐based inventories (e.g., eDNA).

The reactivation of TERT is associated with poor outcome in papillary thyroid cancer (PTC). Extra-telomeric functions of TERT were reported, with a protective role against oxidative stress (OS). The aim of the present study was to explore the extra-nuclear TERT localization in PTC and its role in cancer progression. TERT nuclear export under OS were analyzed in K1 PTC cell line. We investigated the role of different TERT localizations using specific TERT constructs that limit its localization to the nucleus or to the mitochondria. The effect of SRC kinase inhibitor PP2, which reduces TERT nuclear export, was investigated as well. Moreover, TERT localization was analyzed in 39 PTC tissues and correlated with the genetic profile and the level of OS, DNA damage and apoptosis in the tumors and with the clinical characteristics of the patients. We demonstrated that TERT is exported from the nucleus in response to OS induced either from H2O2 or the BRAF inhibitor PLX4720. We proved that extra-nuclear TERT reduces mitochondrial OS and induces mitochondrial fragmentation. Moreover, limiting mitochondrial TERT localization reduced proliferation, migration, AKT phosphorylation and glycolysis and increased DNA damage and p21 expression. Finally, in PTC tissues the fraction of mitochondrial/nuclear TERT resulted inversely correlated with OS and p21 expression and associated with tumor persistence. In conclusion, our data indicate that extra-nuclear TERT is involved in reducing the effect of excessive OS, thus promoting cancer cell survival. Extra-nuclear TERT may thus represent a marker of cancer progression and a possible therapeutic target in PTC. [ABSTRACT FROM AUTHOR]

In the field of contaminated site remediation, risk analyses can be carried out by the use of appropriate mathematical models, based on simplified hypotheses of real sites. The possibility to have shared and accurate analytical methods is an important challenge for both routine laboratories and supervisory institutions. Although official methods (e.g., APH2009) are already available, they are lacking in some aspects, such as applicability to all the different sampling and analysis media and ease of use in routine analysis. Here, we report our recent advances in the implementation of an empirical method for hydrocarbon speciation in an air matrix, previously developed by the authors and published in 2015. The validation results led to a coefficient of variation (CV%) between 10–15% for the hydrocarbon fractions investigated (C5-C8 aliphatic, C9-C12 aliphatic, C9-C10 aromatic and C11-C12 aromatic) and recovery of ≤20%, in agreement with the required characteristics for the analytical methods. Several real samples were analyzed by the proposed method and the results were compared to those obtained by the official approach. The comparison led to an average bias (that is, the difference between the results from the developed method and those from the conventional one) of about 10%, confirming that the innovative approach is robust, accurate and can be applied to all the analytical media used for air sampling, such as soil gas.

Objective: The major strengths of surgical treatment of benign prostatic hyperplasia with laser are reduced morbidity compared to endoscopic resec-tion. No studies analysed the different risk of intra/peri-opera-tive events between patients undergoing Thulium and GreenLight procedures. Materials and methods: We retrospectively reviewed 100 con-secutive cases undergoing GreenLight vaporization and Thulium procedures performed during the learning curve of two expert endoscopic surgeons. Pre-operative data, intra and post-opera-tive events at 90 days were analysed. Results: Patients on antiplatelet/anticoagulant therapy were pre-dominant in the Green group (p < 0.0001). Rates of blood trans-fusion (p < 0.0038), use of resectoscope (p < 0.0086), and tran-sient stress urinary incontinence were statistically higher in the Thulium group. On the contrary conversions to TURP (p < 0.023) were more frequent in GreenLight patients. Readmissions were more frequently necessary in GreenLight group (24%) vs. Thulium group (26.6%). The overall complica-tion rate in GreenLight and Thulium groups were 31% and 53%respectively; Clavien 3b complications were 13% in Thulium patients versus 1% in GreenLight patients. Conclusions: GreenLight and Thulium treatments show similar safety profiles. Randomized controlled trial are needed to better clarify the rate of major complications in Thulium group, and the incidence of post-operative storage symptoms in these patients’ populations.

Mutations in BRAF exon 15 lead to conformational changes in its activation loops, resulting in constitutively active BRAF proteins which are implicated in the development of several human cancer types. Different BRAF inhibitors have been developed and introduced in clinical practice. Identification of BRAF mutations influences the clinical evaluation, treatment, progression and for that reason a sensitive and specific identification of BRAF mutations is on request from the clinic. Here we present the SensiScreen® FFPE BRAF qPCR Assay that uses a novel real-time PCR-based method for BRAF mutation detection based on PentaBases proprietary DNA analogue technology designed to work on standard real-time PCR instruments. The SensiScreen® FFPE BRAF qPCR Assay displays high sensitivity, specificity, fast and easy-to-use. The SensiScreen® FFPE BRAF qPCR Assay was validated on two different FFPE tumour biopsy cohorts, one cohort included malignant melanoma patients previously analyzed by the Cobas® 4800 BRAF V600 Mutation Test, and one cohort from colorectal cancer patients previously analyzed by mutant-enriched PCR and direct sequencing. All BRAF mutant malignant melanoma patients were confirmed with the SensiScreen® FFPE BRAF qPCR Assay and additional four new mutations in the malignant melanoma cohort were identified. All the previously identified BRAF mutations in the colorectal cancer patients were confirmed, and additional three new mutations not identified with direct sequencing were detected. Also, one new BRAF mutation not previously identified with ME-PCR was found. Furthermore, the SensiScreen® FFPE BRAF qPCR Assay identified the specific change in the amino acid. The SensiScreen® FFPE BRAF qPCR Assay will contribute to a more specific, time and cost saving approach to better identify and characterize mutations in patients affected by cancer, and consequently permits a better BRAF characterization that is fundamental for therapy decision.

Abstract Background Climate and farming systems, several of which are considered as low-input agricultural systems, vary between goat populations from Northern and Southern Italy and have led to different management practices. These processes have impacted genome shaping in terms of inbreeding and regions under selection and resulted in differences between the northern and southern populations. Both inbreeding and signatures of selection can be pinpointed by the analysis of runs of homozygosity (ROH), which provides useful information to assist the management of this species in different rural areas. Results We analyzed the ROH distribution and inbreeding (F ROH) in 902 goats from the Italian Goat Consortium2 dataset. We evaluated the differences in individual ROH number and length between goat breeds from Northern (NRD) and Central-southern (CSD) Italy. Then, we identified the signatures of selection that differentiate these two groups using three methods: ROH, ΔROH, and averaged F ST. ROH analyses showed that some Italian goat breeds have a lower inbreeding coefficient, which is attributable to their management and history. ROH are longer in breeds that are undergoing non-optimal management or with small population size. In several small breeds, the ROH length classes are balanced, reflecting more accurate mating planning. The differences in climate and management between the NRD and CSD groups have resulted in different ROH lengths and numbers: the NRD populations bred in isolated valleys present more and shorter ROH segments, while the CSD populations have fewer and longer ROH, which is likely due to the fact that they have undergone more admixture events during the horizontal transhumance practice followed by a more recent standardization. We identified four genes within signatures of selection on chromosome 11 related to fertility in the NRD group, and 23 genes on chromosomes 5 and 6 related to growth in the CSD group. Finally, we identified 17 genes on chromosome 12 related to environmental adaptation and body size with high homozygosity in both groups. Conclusions These results show how different management practices have impacted the level of genomic inbreeding in two Italian goat groups and could be useful to assist management in a low-input system while safeguarding the diversity of small populations.

Alguns textos, às vezes, ficam à deriva em relação ao conjunto da obra de um autor. Esse parece ser o caso de Cartas de Erasmo que figuram, tradicionalmente, como escritos políticos na obra de José de Alencar. É minha intenção, neste artigo, propor uma releitura desses escritos ao aproximá-los da obra ficcional do autor pela análise de seu gênero literário, a saber, o gênero epistolar. A partir do exame da construção do gênero epistolar em Cartas de Erasmo, depreende-se uma nova camada de sentido vinculada à produção de uma imagem autoral que, desarticulada de um modelo de leitura subordinado a estruturas hierárquicas, ecoa em outros escritos de Alencar, possibilitando, dessa forma, o desenho de uma trama autoral encenada pelo autor de Iracema.

Given the increase in the consumption of packaging and plastic products that generate great amounts of municipal waste, efforts are needed to recycle these materials correctly. For the process to be accessible and environmentally friendly, it is crucial to separate the different types of resins before feeding the recycling chain. This classification is usually carried out manually by the employees of the cooperatives. However, most of the time, it is difficult to identify the separated plastic pieces due to the lack of the symbology of the resin used. The plastic ends up having an inappropriate destination. All usual techniques, such as density and burning tests, and others more refined, require specific equipment, such as Fourier transform infrared spectrometry (FTIR), magnetic resonance imaging (MRI), and image and color identification. Standard methods may fail to provide flexibility, and sophisticated ones may be expensive. The present study proposes to establish a methodology to separate the types of plastic through sound when they are crushed. Audio signals and sound waves differ from one resin to another. Therefore, the audio signals from the crumpled plastic samples of each category were recorded using a smartphone, to create a database. The audio data characteristics were extracted using the Mel-Frequency Cepstral Coefficients (MFCC) technique. Two types of neural networks were used for the classification of the coefficients: the convolutional neural network (CNN) and the recurrent network Long short-term memory (LSTM). The performance of both networks was analyzed through the metrics, accuracy, loss, confusion matrix, and inserting new data not seen in the training to observe if the class correctly classified. The LSTM network performed better than the CNN network, reaching an accuracy of 85% due to working with sequential data. However, when inserting new data in the data set crumpled more slowly than the training data, simulating an unfavorable condition and very likely to occur in the day-to-day cooperatives, the performance of the LSTM network dropped significantly, while CNN reached a still acceptable percentage, proving to be better in these situations.

Abstract Background An isochromosome of the long arm of chromosome 7, i(7)(q10), and an interstitial deletion of the long arm of chromosome 20, del(20)(q), are the most frequent anomalies in the bone marrow of patients with Shwachman-Diamond syndrome, which is caused in most cases by mutations of the SBDS gene. These clonal changes imply milder haematological symptoms and lower risk of myelodysplastic syndromes and acute myeloid leukaemia, thanks to already postulated rescue mechanisms. Results Bone marrow from fourteen patients exhibiting either the i(7)(q10) or the del(20)(q) and coming from two large cohorts of patients, were subjected to chromosome analyses, Fluorescent In Situ Hybridization with informative probes and array-Comparative Genomic Hybridization. One patient with the i(7)(q10) showed a subsequent clonal rearrangement of the normal chromosome 7 across years. Four patients carrying the del(20)(q) evolved further different del(20)(q) independent clones, within a single bone marrow sample, or across sequential samples. One patient with the del(20)(q), developed a parallel different clone with a duplication of chromosome 3 long arm. Eight patients bore the del(20)(q) as the sole chromosomal abnormality. An overall overview of patients with the del(20)(q), also including cases already reported, confirmed that all the deletions were interstitial. The loss of material varied from 1.7 to 26.9 Mb and resulted in the loss of the EIF6 gene in all patients. Conclusions Although the i(7)(q) and the del(20)(q) clones are frequent and clinically benign in Shwachman Diamond-syndrome, in the present work we show that they may rearrange, may be lost and then reconstructed de novo, or may evolve with independent clones across years. These findings unravel a striking selective pressure exerted by SBDS deficiency driving to karyotype instability and to specific clonal abnormalities.

Gastric leak is a serious complication of sleeve gastrectomy with a well-documented morbidity and mortality. Depending on the series the leak rate ranges between 1 and 5%. The treatment of sleeve gastrectomy leak is still challenging. Different procedures have been described in management of gastric leak, both surgical and endoscopic. The treatment of gastric leaks depends on the extent of the staple-line leak, the site of the leak and its association with stenosis. As published data are limited, there are no still standardized guidelines on best treatment. One of the most commonly used option in the treatment of gastric leak is esophageal stent. Its success rate reaches 70–80% but it is burdened by some complications. Stent migration is the most common complication in the placement of esophageal stent.We present a challenging surgical in which case the use of an esophageal stent for the treatment of a sleeve gastrectomy leak gained the resolution of the leak but was complicated by bowel obstruction due to migration of the stent.

Abstract Background The present study evaluated the relative survival benefits associated with enasidenib and current standard of care (SoC) therapies for patients with relapsed/refractory (R/R) acute myeloid leukemia (AML) and an isocitrate dehydrogenase 2 (IDH2) mutation who are ineligible for hematopoietic stem cell transplantation (HSCT). Methods Propensity score matching (PSM) analysis compared survival outcomes observed with enasidenib 100 mg daily in the phase I/II AG221‐C‐001 trial and SoC outcomes obtained from a real‐world chart review of patients in France. Results Before matching, enasidenib (n = 195) was associated with numerically improved overall survival (OS) relative to SoC (n = 80; hazard ratio [HR], 0.82; 95% confidence interval [CI], 0.61–1.11). After matching and adjusting for covariates (n = 78 per group), mortality risk was significantly lower with enasidenib than with SoC (HR, 0.67; 95% CI, 0.47–0.97). The median OS was 9.26 months for enasidenib (95% CI, 7.72–13.24) and 4.76 months for SoC (95% CI, 3.81–8.21). Results remained robust across all sensitivity analyses conducted. Conclusions PSM analyses indicate that enasidenib significantly prolongs survival relative to SoC among patients with R/R AML and an IDH2 mutation who are ineligible for HSCT. Future prospective studies are needed to validate these findings using other data sources and to assess the comparative efficacy of enasidenib for other treatment outcomes.

With the increasing environmental awareness, in many applications, ranging from agriculture to industry and logistics, a wider and wider use of eco-friendly fluids is desirable. Although the chemical and biological aspects related to environmental compatibility have been extensively investigated by industries and researchers for obvious environmental reasons, not much literature is available on the performance of hydraulic components and systems operating with eco-friendly fluids, especially on the possible degradation of performance due to fluid aging. This work is aimed at studying the influence of eco-friendly fluids on the performance of external gear pumps for compact mobile hydraulic power units, which are among the most widespread hydraulic devices in the world, for their cost-effective and flexible construction. Once the experimental set-up is implemented to be well representative of the hydraulic power packs’ typical arrangement, pump performance is investigated. Pump energy performance is obtained in terms of volumetric efficiency and torque efficiency. Alongside the traditional fluid, two types of eco-friendly fluid available in the market are tested. Once the comparison is complete, the investigations are devoted to highlighting the impact of fluid aging on the pump performance. The fluids were aged through 2000 h operation under heavy-duty thermo-mechanical stress on a separate set-up and, afterwards, the pump performance was tested again with aged fluids. The results allow the assessment of the influence of different fluids on pump performance and a comparison of the impact of new versus aged eco-friendly fluids. The eco-friendly fluids exert a significant effect on the pump energy profile. The pump overall efficiency increases, marking an up to 5% improvement, depending on the cases. Fluid aging is found to reduce the pump’s overall performance. This paper addresses the key points defining the pump performance and provides new information on the topic. The results are original and represent a fundamental contribution to define the best practices for energy and maintenance management of hydraulic systems and to foster the deployment of further studies on models and simulation tools to catch the effect of the fluid condition.

Ground deformations in urban areas can be the result of a combination of multiple factors and pose several hazards to infrastructures and human lives. In order to monitor these phenomena, Interferometric Synthetic Aperture Radar (InSAR) techniques are applied. The obtained signals record the overlapping of the phenomena, and their separation is a relevant issue. In this framework, we explored a new multi-method approach based on the combination of Principal Component Analysis (PCA), Independent Component Analysis (ICA) and Hierarchal Clustering (HC) on the standardized results to distinguish the main trends and seasonal signals embedded in the time series of ground displacements, to understand spatial-temporal patterns, to correlate ground deformation phenomena with geological and anthropogenic factors, and to recognize the specific footprints of different ground deformation phenomena. This method allows us to classify the ground deformations at the site scale in the metropolitan area of Naples, which is affected by uplift cycles, subsidence, cavity instabilities and sinkholes. At the local scale, the results allow a kinematic classification using the extracted components and considering the effect of the radius of influence generated by each cavity, as it is performed from a theoretical point of view when the draw angle is considered. According to the results, among the classified cavities, 2% were assigned to subsidence and 11% to uplift kinematics, while the remaining were found to be stable. Furthermore, our results show that the centering of the Spatial-PCA (S-PCA) is representative of the region’s main trend, whereas Temporal-PCA (T-PCA) gives information about the displacement rates identified by each component.

Abstract Background Post-trauma bleeding induces an acute deficiency in clotting factors, which promotes bleeding and hemorrhagic shock. However, early plasma administration may reduce the severity of trauma-induced coagulopathy (TIC). Unlike fresh frozen plasma, which requires specific hospital logistics, French lyophilized plasma (FLYP) is storable at room temperature and compatible with all blood types, supporting its use in prehospital emergency care. We aim to test the hypothesis that by attenuating TIC, FLYP administered by prehospital emergency physicians would benefit the severely injured civilian patient at risk for hemorrhagic shock. Methods/design This multicenter randomized clinical trial will include adults severely injured and at risk for hemorrhagic shock, with a systolic blood pressure 1.1. Two parallel groups of 70 patients will receive either FLYP or normal saline in addition to usual treatment. The primary endpoint is the International Normalized Ratio (INR) at hospital admission. Secondary endpoints are transfusion requirement, length of stay in the intensive care unit, survival rate at day 30, usability and safety related to FLYP use, and other biological coagulation parameters. Conclusion With this trial, we aim to confirm the efficacy of FLYP in TIC and its safety in civilian prehospital care. The study results will contribute to optimizing guidelines for treating hemorrhagic shock in civilian settings. Trial registration ClinicalTrials.gov, NCT02736812. Registered on 13 April 2016. The trial protocol has been approved by the French ethics committee (CPP 3342) and the French Agency for the Safety of Medicines and Health Products (IDRCB 2015-A00866–43).

Rosaria Di Lorenzo,1 Nicoletta Frattini,2 Diego Dragone,3 Riccardo Farina,3 Filippa Luisi,3 Silvia Ferrari,3 Geminiano Bandiera,4 Sergio Rovesti,5 Paola Ferri5 1Psychiatric Intensive Treatment Facility, Mental Health and Drug Abuse Department of AUSL-Modena, Modena, Italy; 2Department of Biomedical, Metabolic and Neural Sciences, School of Nursing, University of Modena and Reggio Emilia, Modena, Italy; 3Department of Biomedical, Metabolic and Neural Sciences, School of Psychiatry, University of Modena and Reggio Emilia, Modena, Italy; 4Emergency Room and Emergency Medicine Unit, General Hospital of Baggiovara, AOU of Modena, Modena, Italy; 5Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Modena, ItalyCorrespondence: Rosaria Di LorenzoPsychiatrist, Psychiatric Intensive Treatment Facility, Mental Health and Drug Abuse Department of AUSL-Modena, Via Paul Harris, 175, Modena, 41122, ItalyEmail r.dilorenzo@ausl.mo.itBackground: The new SARS-CoV-2 has caused an ongoing pandemic. Health prevention measures to contain the outbreak are profoundly affecting the physical and mental health as well as personal freedom of the population.Aim: To evaluate psychiatric emergencies in a 6-month period during the COVID-19 pandemic in 2020 compared to those of the corresponding period of the previous year.Methods: This monocentric observational study preliminarily collected variables of the urgent psychiatric consultations (UPCs) carried out in emergency room (ER) from 1-3-2020 to 31-8-2020 and the socio-demographic and clinical characteristics of patients who required UPCs in the 6-month period, comparing these data with those collected from 1-3-2019 to 31-8-2019. The data, collected in alpha-numeric code, were statistically analyzed through STATA 12-2011.Results: This research reported a reduction of both UPCs and hospital psychiatric admissions. Concomitantly, we observed an increase of UPCs required by people already being treated by psychiatric and other health services, residents in psychiatric facilities and non-Italians. In 2020, differently from 2019, the most frequent reasons for urgent psychiatric consultations were aggressive behavior and adjustment disorders with anxiety and depressive mood.Conclusion: This preliminary study suggests that, during the COVID-19 epidemic, urgent psychiatric consultations in ER were reduced, except for the most vulnerable people due to their clinical and/or social conditions.Keywords: psychiatric emergencies, urgent psychiatric consultations, COVID-19 pandemic