SUPREME-HN: a retrospective biomarker study assessing the prognostic value of PD-L1 expression in patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck

Biomarcador; Carcinoma de células escamosas de cabeza y cuello; PD-L1Biomarker; Head and neck squamous cell carcinoma; PD-L1Biomarcador; Carcinoma de cèl·lules escamoses de cap i coll; PD-L1Background Programmed cell death ligand-1 (PD-L1) expression on tumor cells (TCs) is associated with improved survival in patients with head and neck squamous cell carcinoma (HNSCC) treated with immunotherapy, although its role as a prognostic factor is controversial. This study investigates whether tumoral expression of PD-L1 is a prognostic marker in patients with recurrent and/or metastatic (R/M) HNSCC treated with standard chemotherapy. Methods This retrospective, multicenter, noninterventional study assessed PD-L1 expression on archival R/M HNSCC tissue samples using the VENTANA PD-L1 (SP263) Assay. PD-L1 high was defined as PD-L1 staining of ≥ 25% TC, with exploratory scoring at TC ≥ 10% and TC ≥ 50%. The primary objective of this study was to estimate the prognostic value of PD-L1 status in terms of overall survival (OS) in patients with R/M HNSCC. Results 412 patients (median age, 62.0 years; 79.9% male; 88.2% Caucasian) were included from 19 sites in seven countries. 132 patients (32.0%) had TC ≥ 25% PD-L1 expression; 199 patients (48.3%) and 85 patients (20.6%) had TC ≥ 10% and ≥ 50%, respectively. OS did not differ significantly across PD-L1 expression (at TC ≥ 25% cutoff median OS: 8.2 months vs TC < 25%, 10.1 months, P = 0.55) or the ≥ 10% and ≥ 50% cutoffs (at TC ≥ 10%, median OS: 9.6 months vs TC < 10%, 9.4 months, P = 0.32, and at TC ≥ 50%, median OS 7.9 vs TC < 50%, 10.0 months, P = 0.39, respectively). Conclusions PD-L1 expression, assessed using the VENTANA PD-L1 (SP263) Assay, was not prognostic of OS in patients with R/M HNSCC treated with standard of care chemotherapies.This study was sponsored by AstraZeneca. The protocol for this study was developed by the sponsor (AstraZeneca) and advisors. Data were collected collaboratively by the sponsor and clinical investigators. Statisticians employed by the sponsor analyzed the data. All authors participated in the preparation, review, and approval of the manuscript; and decision to submit the manuscript for publication

A Multi-isotopic approach to investigate the influence of land use on nitrate removal in a highly saline lake-aquifer system

Endorheic or closed drainage basins in arid and semi-arid regions are vulnerable to pollution. Nonetheless, in the freshwater-saltwater interface of endorheic saline lakes, oxidation-reduction (redox) reactions can attenuate pollutants such as nitrate (NO3- ). This study traces the ways of nitrogen (N) removal in the Pétrola lake- aquifer system (central Spain), an endorheic basin contaminated with NO3- (up to 99.2 mg/L in groundwater). This basin was declared vulnerable to NO3- pollution in 1998 due to the high anthropogenic pressures (mainly agriculture and wastewaters). Hydrochemical, multi-isotopic (δ18ONO3, δ15NNO3, δ13CDIC, δ18OH2O, and δ2HH2O) and geophysical techniques (electrical resistivity tomography) were applied to identify the main redox processes at the freshwater-saltwater interface. The results showed that the geometry of this interface is influenced by land use, causing spatial variability of nitrogen biogeochemical processes over the basin. In the underlying aquifer, NO3- showed an average concentration of 38.5 mg/L (n = 73) and was mainly derived from agricultural inputs. Natural attenuation of NO3- was observed in dryland farming areas (up to 72%) and in irrigation areas (up to 66%). In the Pétrola Lake, mineralization and organic matter degradation in lake sediment play an important role in NO3- reduction. Our findings are a major step forward in understanding freshwater-saltwater interfaces as reactive zones for NO3- attenuation. We further emphasize the importance of including a land use perspective when studying water quality-environmental relationships in hydrogeological systems dominated by density- driven circulation

Tribocorrosion behavior of new martensitic stainless steels in sodium chloride solution

The tribo-electrochemical behavior of two new martensitic stainless steels in a 3% NaCI solution has been investigated. Different electrochemical and surface analysis techniques (Scanning Electron Microscopy, Focused Ion Beam) were discussed to analyze the influence of the effect of the electrochemical conditions on friction and wear, and to elucidate involved wear mechanisms (plastic deformation, plastic shakedown and low-cycle fatigue). The selected stainless steels degrade through a delamination type of wear mechanism. The effects of the applied potential on wear are related to the formation of a passive film which alters the mechanical behavior of the surface and subsurface of the materials to promote wear. A coefficient of friction below 0.6 promotes nanowear, and a transition was observed when the coefficient of friction exceeded that value. (C) 2016 Elsevier B.V. All rights reserved.The authors would like to thank to BPI, Region Centre and Tours Plus for support of this research. This work is done under the project FUI 11 Mekinox.Dalmau Borrás, A.; Rmili, W.; Richard, C.; Igual Muñoz, AN. (2016). Tribocorrosion behavior of new martensitic stainless steels in sodium chloride solution. Wear. 368:146-155. doi:10.1016/j.wear.2016.09.002S14615536

Anti-trbc1 antibody-based flow cytometric detection of t-cell clonality: Standardization of sample preparation and diagnostic implementation

© 2021 by the authors.A single antibody (anti-TRBC1; JOVI-1 antibody clone) against one of the two mutually exclusive T-cell receptor β-chain constant domains was identified as a potentially useful flow-cytometry (FCM) marker to assess Tαβ-cell clonality. We optimized the TRBC1-FCM approach for detecting clonal Tαβ-cells and validated the method in 211 normal, reactive and pathological samples. TRBC1 labeling significantly improved in the presence of CD3. Purified TRBC1+ and TRBC1− monoclonal and polyclonal Tαβ-cells rearranged TRBJ1 in 44/47 (94%) and TRBJ1+TRBJ2 in 48 of 48 (100%) populations, respectively, which confirmed the high specificity of this assay. Additionally, TRBC1+/TRBC1− ratios within different Tαβ-cell subsets are provided as reference for polyclonal cells, among which a bimodal pattern of TRBC1-expression profile was found for all TCRVβ families, whereas highly-variable TRBC1+/TRBC1− ratios were observed in more mature vs. naïve Tαβ-cell subsets (vs. total T-cells). In 112/117 (96%) samples containing clonal Tαβ-cells in which the approach was validated, monotypic expression of TRBC1 was confirmed. Dilutional experiments showed a level of detection for detecting clonal Tαβ-cells of ≤10−4 in seven out of eight pathological samples. These results support implementation of the optimized TRBC1-FCM approach as a fast, specific and accurate method for assessing T-cell clonality in diagnostic-FCM panels, and for minimal (residual) disease detection in mature Tαβ+ leukemia/lymphoma patients.This work was supported by the CB16/12/00400 (CIBERONC) and PI20-01346 grants, from the Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación (Madrid, Spain) and FONDOS FEDER, and by the EuroFlow Foundation (Leiden, The Netherlands). N. Muñoz-García is supported by a pre-doctoral grant (Ref. IBPredoc17/00012) from IBSAL (Salamanca, Spain). M. Lima, N. Villamor, A.W. Langerak, J.J.M. van Dongen, A. Orfao, and J. Almeida are members of the EuroFlow Consortiu

Classical operators on the Hörmander algebras

We study the integration operator, the differentiation operator and more general differential operators on radial Fr´echet or (LB) H¨ormander algebras of entire functions. We analyze when these operators are power bounded, hypercyclic and (uniformly) mean ergodic.This research was partially supported by MEC and FEDER Project MTM2010-15200. The research of M. J. Beltran was also supported by grant F.P.U. AP2008-00604 and Programa de Apoyo a la Investigacion y Desarrollo de la UPV PAID-06-12, and the research of J. Bonet and C. Fernandez, by GVA under Project PROMETEOII/2013/013.Beltrán Meneu, MJ.; Bonet Solves, JA.; Fernández, C. (2015). Classical operators on the Hörmander algebras. Discrete and Continuous Dynamical Systems - Series A. 35(2):637-652. https://doi.org/10.3934/dcds.2015.35.637S63765235

Utjecaj buke u okolišu na uzrujanost odraslih stanovnika Skopja: presječno istraživanje

The aim of this study was to identify noise exposure indicators during day and night in the city of Skopje and to see if there is an association between these noise exposure indicators and annoyance. We have performed noise measurements and interviewed 510 adult subjects, using a questionnaire, prepared according to the ISO/TS-15666 standard. Average noise level over the day (Lday) was (62±6.45) dB(A) and over night (Lnight) (56±6.52) dB(A). Thirteen percent of subjects reported a high level, and 33.5 % moderate level of annoyance. The most annoying noise sources were construction activities (34 % of the subjects), road traffic (24 %), and leisure/entertainment activities (18 %). We found a significant association between exposure to Lday in the range 61 dB(A) to 65 dB(A) and annoyance in the exposed population (chi-square=86.14; p<0.001; Spearman’s R=0.45; p<0.05). During the night time annoyance was reported with exposure to Lnight above 46 dB(A). Levels of annoyance in Macedonia are similar to levels in developed European countries. Differences are in the source of noise. This study has shown that environmental noise is a significant hazard in urban environments, and assessment of annoyance may prove a useful tool for town planners and public health policy makers.Cilj ovog ispitivanja bio je utvrditi dnevne i noćne razine buke u Skopju te njihovu povezanost s osjećajem uzrujanosti u izloženoj populaciji. Provedena su mjerenja buke te razgovori s 510 odraslih ispitanika s pomoću upitnika sastavljenog prema normi ISO/TS-15666. Prosječna dnevna razina buke iznosila je (62±6,45) dB(A), a noćna (56±6,52) dB(A). Trinaest posto ispitanika iskazalo je izrazitu, a 33,5 % umjerenu uzrujanost. Ispitanicima je najviše smetala buka s gradilišta (34 %), prometna buka (24 %) te buka proizišla iz aktivnosti u slobodnome vremenu (18 %). Utvrdili smo statistički značajnu povezanost između dnevne izloženosti buci u rasponu od 61 dB(A) do 65 dB(A) i uzrujanosti (hi-kvadrat=86,14; p<0,001) te statistički značajnu korelaciju (R=0,45; p<0,05). Povezanost između izloženosti noćnoj buci i uzrujanosti utvrđena je već pri 46 dB(A), a napose pri >56 dB(A), uz značajnu korelaciju (R=0,04; p<0,05). Razine uzrujanosti stanovnika Skopja zbog buke slične su onima u razvijenim europskim zemljama. Postoje međutim razlike u izvorima buke, koji su u našem ispitivanju ponajviše građevinske djelatnosti, cestovni promet te buka proizišla iz aktivnosti u slobodno vrijeme. Istraživanje je pokazalo da je procjena uzrujanosti stanovništva vrijedan podatak koji može poslužiti kod izrade urbanističkih planova i javnozdravstvene politike

Diagnostic Utility of Measuring Cerebral Atrophy in the Behavioral Variant of Frontotemporal Dementia and Association With Clinical Deterioration

Can widely available measures of atrophy on magnetic resonance imaging increase diagnostic certainty of underlying frontotemporal lobar degeneration (FTLD) and estimate clinical deterioration in the behavioral variant of frontotemporal dementia (bvFTD)? This diagnostic/prognostic study investigated the clinical utility of 5 validated visual atrophy scales (VAS) and the Magnetic Resonance Parkinsonism Index. When combined, VAS showed excellent diagnostic performance for differentiating between bvFTD with high and low confidence of FTLD and for the estimation of longitudinal clinical deterioration, whereas the Magnetic Resonance Parkinsonism Index was increased in bvFTD with underlying 4-repeat tauopathies. These findings suggest that, in bvFTD, VAS can be used to increase diagnostic certainty of underlying FTLD and estimate longitudinal clinical deterioration. This diagnostic/prognostic study assesses the utility of 6 visual atrophy scales and the Magnetic Resonance Parkinsonism Index in patients with behavioral variant frontotemporal dementia to distinguish those with high vs low confidence of frontotemporal lobar degeneration. The presence of atrophy on magnetic resonance imaging can support the diagnosis of the behavioral variant of frontotemporal dementia (bvFTD), but reproducible measurements are lacking. To assess the diagnostic and prognostic utility of 6 visual atrophy scales (VAS) and the Magnetic Resonance Parkinsonism Index (MRPI). In this diagnostic/prognostic study, data from 235 patients with bvFTD and 225 age- and magnetic resonance imaging-matched control individuals from 3 centers were collected from December 1, 1998, to September 30, 2019. One hundred twenty-one participants with bvFTD had high confidence of frontotemporal lobar degeneration (FTLD) (bvFTD-HC), and 19 had low confidence of FTLD (bvFTD-LC). Blinded clinicians applied 6 previously validated VAS, and the MRPI was calculated with a fully automated approach. Cortical thickness and subcortical volumes were also measured for comparison. Data were analyzed from February 1 to June 30, 2020. The main outcomes of this study were bvFTD-HC or a neuropathological diagnosis of 4-repeat (4R) tauopathy and the clinical deterioration rate (assessed by longitudinal measurements of Clinical Dementia Rating Sum of Boxes). Measures of cerebral atrophy included VAS scores, the bvFTD atrophy score (sum of VAS scores in orbitofrontal, anterior cingulate, anterior temporal, medial temporal lobe, and frontal insula regions), the MRPI, and other computerized quantifications of cortical and subcortical volumes. The areas under the receiver operating characteristic curve (AUROC) were calculated for the differentiation of participants with bvFTD-HC and bvFTD-LC and controls. Linear mixed models were used to evaluate the ability of atrophy measures to estimate longitudinal clinical deterioration. Of the 460 included participants, 296 (64.3%) were men, and the mean (SD) age was 62.6 (11.4) years. The accuracy of the bvFTD atrophy score for the differentiation of bvFTD-HC from controls (AUROC, 0.930; 95% CI, 0.903-0.957) and bvFTD-HC from bvFTD-LC (AUROC, 0.880; 95% CI, 0.787-0.972) was comparable to computerized measures (AUROC, 0.973 [95% CI, 0.954-0.993] and 0.898 [95% CI, 0.834-0.962], respectively). The MRPI was increased in patients with bvFTD and underlying 4R tauopathies compared with other FTLD subtypes (14.1 [2.0] vs 11.2 [2.6] points; P < .001). Higher bvFTD atrophy scores were associated with faster clinical deterioration in bvFTD (1.86-point change in Clinical Dementia Rating Sum of Boxes score per bvFTD atrophy score increase per year; 95% CI, 0.99-2.73; P < .001). Based on these study findings, in bvFTD, VAS increased the diagnostic certainty of underlying FTLD, and the MRPI showed potential for the detection of participants with underlying 4R tauopathies. These widely available measures of atrophy can also be useful to estimate longitudinal clinical deterioration