Expression of TILs and Patterns of Gene Expression from Paired Samples of Malignant Pleural Mesothelioma (MPM) Patients.

MPM is an aggressive disease with an immunosuppressive tumor microenvironment, and interest in exploring immunotherapy in this disease has been increasing. In the first line of treatment, the combination of nivolumab and ipilimumab demonstrated an improvement in survival over chemotherapy. The presence of TILs has been recognized as a marker of antitumor immune response to chemotherapy in solid tumors.

As and S speciation in a submarine sulfide mine tailings deposit and its environmental significance: The study case of Portmán Bay (SE Spain).

The dumping of an estimated amount of 57 million tons of hazardous sulfide mine waste from 1957 to 1990 into Portmán's Bay (SE Spain) caused one of the most severe cases of persistent anthropogenic impact in Europe's costal and marine environments. The resulting mine tailings deposit completely infilled Portmán's Bay and extended seawards on the continental shelf, bearing high levels of metals and As. The present work, where Synchrotron XAS, XRF core scanner and other data are combined, reveals the simultaneous presence of arsenopyrite (FeAsS), scorodite (FeAsO₄·2H₂O), orpiment (AsS) and realgar (AsS) in the submarine extension of the mine tailings deposit.

Dynamic changes in circulating tumor DNA assessed by shallow whole-genome sequencing associate with clinical efficacy of checkpoint inhibitors in NSCLC.

Immune checkpoint inhibitors (ICIs) targeting the PD-1/PD-L1 axis are the main therapeutic option for patients with advanced non-small cell lung cancer (NSCLC) without a druggable oncogenic alteration. Nevertheless, only a portion of patients benefit from this type of treatment. Here, we assessed the value of shallow whole-genome sequencing (sWGS) on plasma samples to monitor ICI benefit.

Human Metastatic Cholangiocarcinoma Patient-Derived Xenografts and Tumoroids for Preclinical Drug Evaluation.

Purpose: Cholangiocarcinoma (CCA) is usually diagnosed at advanced stages, with limited therapeutic options. Preclinical models focused on unresectable metastatic CCA are necessary to develop rational treatments. Pathogenic mutations in IDH1/2, ARID1A/B, BAP1, and BRCA1/2 have been identified in 30%-50% of patients with CCA.

DSTYK inhibition increases the sensitivity of lung cancer cells to T cell-mediated cytotoxicity.

Lung cancer remains the leading cause of cancer-related death worldwide. We identify DSTYK, a dual serine/threonine and tyrosine non-receptor protein kinase, as a novel actionable target altered in non-small cell lung cancer (NSCLC). We also show DSTYK's association with a lower overall survival (OS) and poorer progression-free survival (PFS) in multiple patient cohorts.

Overview of Checkpoint Inhibitors Mechanism of Action: Role of Immune-Related Adverse Events and Their Treatment on Progression of Underlying Cancer.

In recent years, immunotherapy-based regimens have been included into the treatment's algorithm of several cancer types. Programmed death-1 (PD-1) and cytotoxic T lymphocyte antigen-4 (CTLA-4) interact with their ligands found on the surface of antigen presenting cells (APC) or tumor cells (PD-L1/2 and CD80/86). Through these interactions, stimulatory or inhibitory signals are established.

High levels of chromosomal aberrations negatively associate with benefit to checkpoint inhibition in NSCLC.

Background: Immune checkpoint inhibitors (ICIs) targeting the programmed cell death 1/programmed death-ligand 1 axis have transformed the management of advanced non-small cell lung cancer (NSCLC). However, many patients do not benefit from this type of treatment, and thus several molecular biomarkers of benefit have been explored. The value of somatic copy number alterations (SCNAs) burden remains elusive.

Efficacy of chemotherapy for malignant pleural mesothelioma according to histology in a real-world cohort.

CheckMate 743 trial demonstrated survival benefit of immunotherapy in first line in MPM with some differences in the efficacy of chemotherapy according to histology. The objective of this study is to characterize the impact of chemotherapy according to histology in patients diagnosed with MPM at our institution. Clinical records of all MPM patients diagnosed at Vall d'Hebron University Hospital between November 2002 and April 2020 were reviewed.

Multiproxy characterization of sedimentary facies in a submarine sulphide mine tailings dumping site and their environmental significance: The study case of Portmán Bay (SE Spain).

Mining activities are essential to our society, but ore extraction and treatment produce waste that must be stored in safe places without harm to the environment. For a long time, seafloor disposal has been viewed as a cheap option with barely visible impacts. In Portmán Bay, SE of Spain, large amounts of tailings from open pit sulphide mining were discharged directly into the coastal sea over 33 years, thus forming a massive deposit that completely infilled the bay and expanded seawards over the inner continental shelf.

What Happened in That Pit? An Archaeozoological and GIS Approach to Study an Accumulation of Animal Carcasses at the Roman Villa of Vilauba (Catalonia).

Some of the deposits of animal remains documented throughout prehistory and history are clearly something other than ordinary waste from meat consumption. For the Roman period and based on their characteristics, these assemblages have been classified as butchery deposits, raw material deposits, deposits created for the hygienic management and disposal of animal carcasses, or ritual deposits. However, some are difficult to classify, and the parameters that define each of them are not clear.

Interrelations between Patients' Clinicopathological Characteristics and Their Association with Response to Immunotherapy in a Real-World Cohort of NSCLC Patients.

Immune checkpoint inhibitors (ICIs) have transformed non-small cell lung cancer (NSCLC) treatment. Unfortunately, only some patients benefit from these therapies. Thus, certain clinicopathological characteristics of the patients have been proposed as biomarkers of ICIs response.

Stabilisation of half MCM ring by Cdt1 during DNA insertion.

Origin licensing ensures precise once per cell cycle replication in eukaryotic cells. The Origin Recognition Complex, Cdc6 and Cdt1 load Mcm2-7 helicase (MCM) into a double hexamer, bound around duplex DNA. The complex formed by ORC-Cdc6 bound to duplex DNA (OC) recruits the MCM-Cdt1 complex into the replication origins.

Processes driving seagrass soils composition along the western Mediterranean: The case of the southeast Iberian Peninsula.

Seagrasses are distributed all along the coast of the Mediterranean Sea being Posidonia oceanica and Cymodocea nodosa the most common species. They promote sedimentation, leading to the formation of well-structured soils. Over the last decade, a growing attention has been paid to their role as CO sinks in the form of organic carbon (C) and to their use as environmental archives.

Variable interplay of UV-induced DNA damage and repair at transcription factor binding sites.

An abnormally high rate of UV-light related mutations appears at transcription factor binding sites (TFBS) across melanomas. The binding of transcription factors (TFs) to the DNA impairs the repair of UV-induced lesions and certain TFs have been shown to increase the rate of generation of these lesions at their binding sites. However, the precise contribution of these two elements to the increase in mutation rate at TFBS in these malignant cells is not understood.

Molecular profiling of long-term responders to immune checkpoint inhibitors in advanced non-small cell lung cancer.

Immunotherapy has transformed advanced non-small cell lung cancer (NSCLC) treatment strategies and has led to unprecedented long-lasting responses in some patients. However, the molecular determinants driving these long-term responses remain elusive. To address this issue, we performed an integrative analysis of genomic and transcriptomic features of long-term immune checkpoint inhibitors (ICIs)-associated responders.

A small Cretaceous crocodyliform in a dinosaur nesting ground and the origin of sebecids.

Sebecosuchia was a group of highly specialized cursorial crocodyliforms that diversified during the Cretaceous and persist until the end of the Miocene. Their unique combination of cranial and post-cranial features indicates that they were active terrestrial predators that occupied the apex of the Late Cretaceous terrestrial ecosystems, even competing with theropod dinosaurs. Here, we report the discovery of the earliest sebecid worldwide, and the first from Eurasia, Ogresuchus furatus gen.

Clinical Prognosis of Right-Sided Infective Endocarditis not Associated with Cardiac Devices or Intravenous Drug use: a Cohort Study and Meta-Analysis.

Right-sided infective endocarditis (RSIE), classically associated with intravenous drug use or intracardiac devices, is considered a good-prognosis infective endocarditis (IE) form. However, predisposing factors and prognosis for "NODID" RSIE (NOt associated with cardiac Devices or Intravenous Drug use) remain unclear. The aim of this study was to evaluate predisposing factors and prognosis of NODID RSIE compared to other RSIE forms.

Calibrating high resolution XRF core scanner data to obtain absolute metal concentrations in highly polluted marine deposits after two case studies off Portmán Bay and Barcelona, Spain.

X-ray fluorescence core scanners (XRF-CS) allow rapid, non-destructive, continuous and high-resolution analyses of the elemental composition of sediment cores, providing large sets of semi-quantitative data. These data can be converted to quantitative data through the linear regression approach using a relatively small number of discrete samples analyzed by techniques providing absolute concentrations. However, a precise characterization of the errors associated with the linear function is required to evaluate the quality of the calibrated element concentrations.

X-ray microtomographic characterization of highly rough titanium cold gas sprayed coating for identification of effective surfaces for osseointegration.

A highly rough titanium coating obtained by Cold Gas Spray (CGS) has been characterized by means of high-resolution 3D microtomography (micro-CT) with the aim to evaluate its open and close porosity for possible use in orthopaedic implants to promote osseointegration. Micro-CT allowed a qualitative and quantitative description of the main features, morphology of the pores and surface roughness of the coating. Several numerical values were obtained to describe size, form and distribution of the closed/inner and open/outer pores.

Micro-computed tomography assessment of different obturation techniques for filling lateral canals.

Background: The aim of this study was to evaluate obturation depth and volume by means of micro-CT when filling lateral canals.

Material And Methods: Thirty single-rooted teeth were used. After instrumentation, three artificial lateral canals were created on each mesial and distal surface (one on each third).

Author Correction: Reduced mutation rate in exons due to differential mismatch repair.

In the version of this article initially published, the x axis on the fourth plot in Fig. 2e was incorrectly labeled "H3K36me3 exon-to-intron ratio (lower to higher)." The x axis on this plot should read "Genic H3K36me3 coverage bins (higher to lower)".

Reduced mutation rate in exons due to differential mismatch repair.

While recent studies have identified higher than anticipated heterogeneity of mutation rate across genomic regions, mutations in exons and introns are assumed to be generated at the same rate. Here we find fewer somatic mutations in exons than expected from their sequence content and demonstrate that this is not due to purifying selection. Instead, we show that it is caused by higher mismatch-repair activity in exonic than in intronic regions.

Corrigendum: A submarine volcanic eruption leads to a novel microbial habitat.

This corrects the article DOI: 10.1038/s41559-017-0144.

A submarine volcanic eruption leads to a novel microbial habitat.

Submarine volcanic eruptions are major catastrophic events that allow investigation of the colonization mechanisms of newly formed seabed. We explored the seafloor after the eruption of the Tagoro submarine volcano off El Hierro Island, Canary Archipelago. Near the summit of the volcanic cone, at about 130 m depth, we found massive mats of long, white filaments that we named Venus's hair.