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The physical effects of climate warming have been well documented, but the biological responses are far less well known, especially at the ecosystem level and at large (intercontinental) scales. Global warming over the next century is generally predicted to reduce food web complexity, but this is rarely tested empirically due to the dearth of studies isolating the effects of temperature on complex natural food webs. To overcome this obstacle, we used 'natural experiments' across 14 streams in Iceland and Russia, with natural warming of up to 20°C above the coldest stream in each high-latitude region, where anthropogenic warming is predicted to be especially rapid. Using biomass-weighted stable isotope data, we found that community isotopic divergence (a universal, taxon-free measure of trophic diversity) was consistently lower in warmer streams. We also found a clear shift towards greater assimilation of autochthonous carbon, which was driven by increasing dominance of herbivores but without a concomitant increase in algal stocks. Overall, our results support the prediction that higher temperatures will simplify high-latitude freshwater ecosystems and provide the first mechanistic glimpses of how warming alters energy transfer through food webs at intercontinental scales., (© 2024 The Author(s). Global Change Biology published by John Wiley & Sons Ltd.)

Objective: Positron Emission Tomography (PET) is a well-known imaging technology for the diagnosis, treatment, and monitoring of several diseases. Most PET scanners use a Ring-Shaped Detector Configuration (RSDC), which helps obtain homogeneous image quality but are restricted to an invariable Field-of-View (FOV), scarce spatial resolution, and low sensitivity. Alternatively, few PET systems use Open Detector Configurations (ODC) to permit an accessible FOV adaptable to different target sizes, thus optimizing sensitivity. Yet, to compensate the lack of angular coverage in ODC-PET, developing a detector with high-timing performance is mandatory to enable Time-of-Flight (TOF) techniques during reconstruction. The main goal of this work is to provide a proof of concept PET scanner appropriate for constructing the new generation of ODC-PET suitable for biopsy guidance and clinical intervention during acquisition. The designed detector has to be compact and robust, and its requirements in terms of performance are spatial and time resolutions < 2 mm and < 200 ps, respectively., Methods: The present work includes a simulation study of an ODC-PET based on 2-panels with variable distance. The image quality (IQ) and Derenzo phantoms have been simulated and evaluated. The phantom simulations have also been performed using a ring-shaped PET for comparison purposes of the ODC approach with conventional systems. Then, an experimental evaluation of a prototype detector that has been designed following the simulation results is presented. This study focused on tuning the ASIC parameters and evaluating the scintillator surface treatment (ESR and TiO 2 ), and configuration that yields the best Coincidence Time Resolution (CTR). Moreover, the scalability of the prototype to a module of 64 × 64mm 2 and its preliminary evaluation regarding pixel identification are provided., Results: The simulation results reported sensitivity (%) values at the center of the FOV of 1.96, 1.63, and 1.18 for panel distances of 200, 250, and 300 mm, respectively. The IQ reconstructed image reported good uniformity (87%) and optimal CRC values, and the Derenzo phantom reconstruction suggests a system resolution of 1.6-2 mm. The experimental results demonstrate that using TiO 2 coating yielded better detector performance than ESR. Acquired data was filtered by applying an energy window of ± 30% at the photopeak level. After filtering, best CTR of 230 ± 2 ps was achieved for an 8 × 8 LYSO pixel block with 2 × 2 × 12mm 3 each. The detector performance remained constant after scaling-up the prototype to a module of 64 × 64mm 2 , and the flood map demonstrates the module's capabilities to distinguish the small pixels; thus, a spatial resolution < 2 mm (pixel size) is achieved., Conclusions: The simulated results of this biplanar scanner show high performance in terms of image quality and sensitivity. These results are comparable to state-of-the-art PET technology and, demonstrate that including TOF information minimizes the image artifacts due to the lack of angular projections. The experimental results concluded that using TiO 2 coating provide the best performance. The results suggest that this scanner may be suitable for organ study, breast, prostate, or cardiac applications, with good uniformity and CRC., (© 2024. The Author(s).)

Warming can have profound impacts on ecological communities. However, explorations of how differences in biogeography and productivity might reshape the effect of warming have been limited to theoretical or proxy-based approaches: for instance, studies of latitudinal temperature gradients are often conflated with other drivers (e.g., species richness). Here, we overcome these limitations by using local geothermal temperature gradients across multiple high-latitude stream ecosystems. Each suite of streams (6-11 warmed by 1-15°C above ambient) is set within one of five regions (37 streams total); because the heating comes from the bedrock and is not confounded by changes in chemistry, we can isolate the effect of temperature. We found a negative overall relationship between diatom and invertebrate species richness and temperature, but the strength of the relationship varied regionally, declining more strongly in regions with low terrestrial productivity. Total invertebrate biomass increased with temperature in all regions. The latter pattern combined with the former suggests that the increased biomass of tolerant species might compensate for the loss of sensitive species. Our results show that the impact of warming can be dependent on regional conditions, demonstrating that local variation should be included in future climate projections rather than simply assuming universal relationships., (© 2024. The Author(s).)

Introduction: Neoadjuvant and adjuvant immune checkpoint blockade (ICB) have recently become standard of care in resectable non-small cell lung cancer (NSCLC). Yet, biomarkers that inform patients who benefit from this approach remain largely unknown. Here, we interrogated the tumor immune microenvironment (TIME) in early-stage NSCLC patients that underwent up-front surgery., Methods: A total of 185 treatment-naïve patients with early-stage NSCLC, that underwent up-front surgical treatment between 2006 and 2018 at Hospital del Mar were included. 124 lung adenocarcinomas (LUADs), and 61 squamous cell carcinoma (LUSCs) were included in a tissue microarray. Immunohistochemistry for CD3, CD4, CD8, CD68, CD80, CD103, FOXP3, PD-1, PD-L1, PD-L2 and HLA class II were evaluated by digital image analysis (QuPath software). TIME was categorized into four groups using PD-L1 expression in tumor cells (<1 % or ≥1 %) and tumor resident memory (CD103 + ) immune cells (using the median as cut-off). We explored the association between different TIME dimensions and patient's clinicopathological features and outcomes., Results: We found increased levels of T cell markers (CD3 + , CD4 + , CD8 + cells), functional immune markers (FOXP3 + cells) as well as, higher HLA-II tumor membrane expression in LUADs compared to LUSCs (p < 0.05 for all). In contrast, LUSCs displayed higher percentage of intratumor macrophages (CD68 + cells) as well as, higher PD-L1 and PD-L2 tumor membrane expression (p < 0.05 for all). Unsupervised analysis revealed three different tumor subsets characterized by membrane tumor expression of PD-L1, PD-L2 and HLA-class II. Enrichment of T cells (CD3 + , CD8 + cells), regulatory T cells (FOXP3 + cells) and macrophages (CD68 + cells) was observed in the CD103 + /PD-L1 + group (p < 0.05 for all). Multivariate analysis showed that infiltration by CD103 + immune cells was associated with improved OS (p = 0.009)., Conclusions: TIME analysis in resected NSCLC highlighted differences by histology, PD-L1 expression and molecular subgroups. Biomarker studies using IHC might aid to individually tailor adjuvant treatment in early-stage NSCLC., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:P. Rocha reports travel support from AstraZeneca. A. Taus reports personal fees and non-financial support from Takeda, Sanofi, Roche, BMS, MSD, GSK, Astrazeneca and Pfizer, outside the submitted work. R. Chalela reports travel and personal fees from Chiesi, GSK and AstraZeneca, outside the submitted work. B. Bellosillo reports grants, personal fees and non-financial support from Roche, grants, personal fees and non-financial support from ThermoFisher, grants, personal fees and non-financial support from Astra-Zeneca, personal fees and non-financial support from Merck-Serono, personal fees and non-financial support from Novartis, personal fees and non-financial support from Qiagen, personal fees and non-financial support from Pfizer, personal fees and non-financial support from BMS. L. Comerma reports personal fees and non-financial support from Roche, personal fees and non-financial support from MSD and personal fees from Diaceutics, outside the submitted work. E. Arriola reports grants, personal fees and non-financial support from Roche, personal fees, and non-financial support from BMS, personal fees and non-financial support from MSD, personal fees from Astra Zeneca, grants and personal fees from Pfizer, personal fees and non-financial support from Boehringer Ingelheim, personal fees and non-financial support from Lilly, personal fees from Takeda, outside the submitted work. Remain authors have no competing interests to declare., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Therapeutic options for patients with relapsed SCLC are limited, and the prognosis in this setting remains poor. While clinical outcomes for frontline treatment have modestly improved with the introduction of immunotherapy, treatment in the second-line setting persists almost unchanged. In this review, current treatment options and recent advances in molecular biology are described. Emerging therapeutic options in this setting, and potential strategies to improve clinical outcomes of these patients are also addressed., Competing Interests: Declaration of Competing Interest AA reports research grants from Celgene, BMS, Ipsen, Roche; honoraria for advisory board participation from BMS, MSD, ROCHE, AstraZeneca, Eli-Lilly. LB received research funding from AstraZeneca, Amgen, Jazz Pharmaceuticals; served as an advisor/consultant for Merck Sharp & Dohme Corp., Arrowhead Pharmaceuticals, Chugai Pharma, AstraZeneca, Abbvie, BeiGene, Jazz Pharmaceuticals, Genentech. RC reports honoraria, consulting or advisory role from AstraZeneca, BMS, Roche, MSD, Boehringer Ingelheim, Takeda, Bayer, Sanofi, Pharmamar, Lilly Oncology, Janssen, Amgen and Novartis. LM, BZ and GL declare no conflicts of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Objective : Time-of-flight positron emission tomography (PET) is the next frontier in improving the effective sensitivity. To achieve superior timing for time-of-flight PET, combined with high detection efficiency and cost-effectiveness, we have studied the applicability of BaF2 in metascintillators driven by the timing of cross-luminescence photon production. Approach : Based on previous simulation studies of energy sharing and analytic multi-exponential scintillation pulse, as well as sensitivity characteristics, we have experimentally tested a pixel of 3 × 3 × 15 mm3 based on 300 μ m BGO and 300 μ m BaF2 layers. To harness the deep ultraviolet cross-luminescent light component, which carries improved timing, we use the FBK VUV SiPM. Metascintillator energy sharing is addressed through a double integration approach. Main results : We reach an energy resolution of 22%, comparable to an 18% resolution of simple BGO pixels using the same readout, through the optimized use of the integrals of the metascintillator pulse in energy sharing calculation. We measure the energy sharing extent of each pulse with a resolution of 25% and demonstrate that experimental and simulation results agree well. Based on the energy sharing, a timewalk correction is applied, exhibiting significant improvements for both the coincidence time resolution (CTR) and the shape of the timing histogram. We reach 242 ps CTR for the entire photopeak, while for a subset of 13% of the most shared events, the CTR value improves to 108 ps, comparable to the 3 × 3 × 5 mm3 LYSO:Ce:Ca reference crystal. Significance : While we are considering different ways to improve further these results, this proof-of-concept demonstrates the applicability of cross-luminescence for metascintillator designs through the application of VUV compatible SiPM coupling, and easily implementable digital algorithms. This is the first test of BaF 2 -based metascintillators of sufficient stoppng power to be included in a PET scanner, demonstrating the industrial applicability of such cross-luminescent metascintillators., (Creative Commons Attribution license.)

EGFR-mutated tumors represent a significant percentage of non-small cell lung cancer. Despite the increasing use of osimertinib, a treatment that has demonstrated an outstanding clinical benefit with a tolerable toxicity profile, EGFR tumors eventually acquire mechanisms of resistance. In the last years, multiple mechanisms of resistance have been identified; however, after progressing on osimertinib, treatment options remain bleak. In this review, we cover the most frequent alterations and potential therapeutic strategies to overcome them.

This article analyzes the perceptions of sexual affective diversity among teachers in Spanish high schools. Specifically, we address LGBTphobia, and teacher intervention and training through a survey study of 119 teachers. We administered a questionnaire to investigate these issues based on other studies. The data were analyzed on the basis of descriptive statistics. We attempted to answer three research questions: How do teachers analyze LGBTphobia in high schools? What is their experience and teaching intervention with regard to affective and sexual diversity? What perception exists in high schools about the need for training and education on affective and sexual diversity? The study concludes that high schools and their communities remain hostile places for LGBT students. Therefore, incorporating training into teaching practice and rethinking pedagogy from a queer perspective is fundamental to building an inclusive educational culture.

Improvements in energy resolution of modern positron emission tomography (PET) detectors have created opportunities to implement energy-based scatter correction algorithms. Here, we use the energy information of auxiliary windows to estimate the scatter component. Our method is directly implemented in an iterative reconstruction algorithm, generating a scatter-corrected image without the need for sinograms. The purpose was to implement a fast energy-based scatter correction method on list-mode PET data, when it was not possible to use an attenuation map as a practical approach for the scatter degradation. The proposed method was evaluated using Monte Carlo simulations of various digital phantoms. It accurately estimated the scatter fraction distribution, and improved the image contrast in the simulated studied cases. We conclude that the proposed scatter correction method could effectively correct the scattered events, including multiple scatters and those originated in sources outside the field of view.

In this work, we propose and analyze a new concept of gamma ray imaging that corresponds to a gamma camera with a mobile collimator, which can be used in vivo, during surgical interventions for oncological patients for localizing regions of interest such as tumors or ganglia. The benefits are a much higher sensitivity, better image quality and, consequently, a dose reduction for the patient and medical staff. This novel approach is a practical solution to the overlapping problem which is inherent to multi-pinhole gamma camera imaging and single photon emission computed tomography and which translates into artifacts and/or image truncation in the final reconstructed image. The key concept consists in introducing a relative motion between the collimator and the detector. Moreover, this design could also be incorporated into most commercially available gamma camera devices, without any excessive additional requirements. We use Monte Carlo simulations to assess the feasibility of such a device, analyze three possible designs and compare their sensitivity, resolution and uniformity. We propose a final design of a gamma camera with a high sensitivity ranging from 0.001 to 0.006 cps/Bq, and a high resolution of 0.5-1.0 cm (FWHM), for source-to-detector distances of 4-10 cm. Additionally, this planar gamma camera provides information about the depth of source (with approximate resolution of 1.5 cm) and excellent image uniformity.

Our aim was to describe the incidence and characteristics of immune-related adverse events (irAEs) in patients with non-small-cell lung cancer (NSCLC) treated with immune checkpoint inhibitors (ICI) and to evaluate their impact on outcome. All cases of NSCLC patients treated with ICIs in the second-line setting between December 2015 and May 2018 were evaluated. Seventy patients were included. Mean age was 65.9 years, and the majority of male ( n  = 53, 75.7%), with PS of 0-1 ( n  = 62, 88.6%) treated with nivolumab ( n  = 51; 72.9%). Thirty-one patients (44.3%) experienced an AE, 5 (7.1%) were grades 3-4. Median OS in patients with AE was 30.1 months (95% CI, 16.7-43.5) compared with 5.1 months (95% CI, 1.2-9.0) in cases without AE (log-rank test: p  = 0.010). The adjusted HR for OS was 0.46 (95% CI, 0.25-0.86) for the irAE occurrence and 3.60 (95% CI, 1.56-8.32) for PS 2-3 group. The development of irAEs was associated with improved patient outcome.

Since March 14, 2020, Spanish citizens have been confined to their homes due to the impact of the COVID-19 pandemic. Participating in musical activities has been associated with reduced anxiety and increased subjective wellbeing. The aim of this study is to analyze how Spanish citizens used music during the lockdown period. We also study perceptions of the impact music has in everyday life, in particular examining the respondents' insights into the effects of listening to music in situations of isolation. The study was conducted using the MUSIVID19 questionnaire administered to a total of 1868 Spanish citizens. The results indicate that during lockdown, respondents perceived an increase in the time they devoted to musical activities such as listening, singing, dancing or playing an instrument. The participants also reported using music to cope with the lockdown, finding that it helped them to relax, escape, raise their mood or keep them company. The findings suggest an improvement in their perception of the value of music in personal and social wellbeing during the lockdown. However, the study reveals significant differences in the use and perceptions of music according to respondents' personal situations. Age and feelings of vulnerability may lead to more conservative uses of musical practice and to more moderate perceptions of the positive values of music., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Cabedo-Mas, Arriaga-Sanz and Moliner-Miravet.)

Introduction: Hyperprogressive disease (HPD) as a consequence of immune checkpoint inhibitors in NSCLC has been reported in multiple studies. However, inconsistent results in incidence and survival outcomes within studies, together with different assessment methods, have led to increasing controversy regarding the concept of HPD., Methods: Consecutive patients treated with nivolumab (N = 42) or docetaxel (N = 37) were evaluated. HPD was quantified by applying three different methods (tumor growth rate [TGR], tumor growth kinetics [TGK], and Response Evaluation Criteria in Solid Tumors version 1.1 [RECIST 1.1]). HPD rates were compared between and within both cohorts using the different methods., Results: Using TGR, TGK, and RECIST 1.1, we identified seven (16.7%), seven (16.7%), and six (14.3%) patients with HPD in the nivolumab cohort and three (8.1%), four (10.8%), and five (13.6%) in the docetaxel cohort, respectively. We observed a higher concordance between TGR and TGK (90.1%) compared with RECIST 1.1 (31.3% and 37.5% with TGR and TGK, respectively). We found no significant differences in the overall survival between patients with progressive disease and HPD in either cohort., Conclusions: TGR and TGK revealed high concordance rates for identifying patients with HPD in NSCLC. The incidence of HPD was numerically higher in patients treated with immune checkpoint inhibitors. Standardization of methods for measuring HPD and its exploration in larger studies are needed to establish its clinical meaning in NSCLC., (© 2020 The Authors.)

In this research the effects of reciprocal peer tutoring on students' mathematics anxiety levels were examined. A pretest posttest with control group design was used at a public middle school in Spain. A total of 420 students in 7th, 8th, and 9th grades participated in the study, of which 215 were female and 205 were male. Students were randomly assigned and equally distributed by course grade (140 in each course grade) and experimental condition (210 in the experimental group and 210 in the control group). Quantitative data were gathered using the Mathematics Anxiety Scale developed by Chiu and Henry (1990). Qualitative information was gathered during eight focus group sessions that were held with students. Two main factors were analyzed using the quantitative and qualitative information: mathematics learning anxiety and mathematics evaluation anxiety. Results were analyzed by gender and course grade. Statistically significant improvements were reported for both male and female students in the experimental group and for each course grade for both factors. No statistically significant differences were reported for students in the control group in any case. A moderate effect size was reported for mathematics evaluation anxiety (Hedge's g = 0.42), and a large effect size was reported for mathematics learning anxiety (Hedge's g = 0.84). Information obtained from the focus groups was consistent with the reported quantitative results. The main conclusion is that peer tutoring may be very beneficial for reducing middle school students' mathematics anxiety, regardless of their gender or grade., (Copyright © 2020 Moliner and Alegre.)

Background: Prostate cancer (PCa) represents one of the most common types of cancers facing the male population. Nowadays, to confirm PCa, systematic or multiparametric MRI-targeted transrectal or transperineal biopsies of the prostate are required. However, due to the lack of an accurate imaging technique capable to precisely locate cancerous cells in the prostate, ultrasound biopsies sample random parts of the prostate and, therefore, it is possible to miss regions where those cancerous cells are present. In spite of the improvement with multiparametric MRI, the low reproducibility of its reading undermines the specificity of the method. Recent development of prostate-specific radiotracers has grown the interest on using positron emission tomography (PET) scanners for this purpose, but technological improvements are still required (current scanners have resolutions in the range of 4-5 mm)., Results: The main goal of this work is to improve state-of-the-art PCa imaging and diagnosis. We have focused our efforts on the design of a novel prostate-dedicated PET scanner, named ProsPET. This system has small scanner dimensions defined by a ring of just 41 cm inner diameter. In this work, we report the design, implementation, and evaluation (both through simulations and real data) of the ProsPET scanner. We have been able to achieve < 2 mm resolution in reconstructed images and high sensitivity. In addition, we have included a comparison with the Philips Gemini-TF scanner, which is used for routine imaging of PCa patients. The ProsPET exhibits better contrast, especially for rod sizes as small as 4.5 mm in diameter. Finally, we also show the first reconstructed image of a PCa patient acquired with the ProsPET., Conclusions: We have designed and built a prostate specific PET system, with a small footprint and improved spatial resolution when compared to conventional whole-body PET scanners. The gamma ray impact within each detector block includes accurate DOI determination, correcting for the parallax error. The potential role of combined organ-dedicated prostate-specific membrane antigen (PSMA) PET and ultrasound devices, as a prebiopsy diagnostic tool, could be used to guide sampling of the most aggressive sites in the prostate.