cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.16501700
title: Molecular underpinnings of glandular tropism in metastatic clear cell renal cell carcinoma: therapeutic implications

description: Glandular metastases (GM) have been associated with improved survival in metastatic clear cell renal cell carcinoma (m-ccRCC). We aimed to molecularly characterize m-ccRCC with GM. We performed a retrospective cohort study on all m-ccRCC patients with available tissue at our institution, diagnosed with metastatic disease from 2000 to 2019. We determined previously described angiogenesis- and immune-related gene expression signatures (GES) and ccrcc molecular subtypes through whole transcriptome RNA sequencing of primary tumors and metastases. We tested differences in GES and molecular subtypes across groups and studied overall (OS) and progression-free survival (PFS) using Kaplan–Meier survival analysis and Cox regression models. Primary tumors of patients who developed GM (<i>n</i> = 55) had higher IMmotion Angio (<i>p</i> p = 0.003) GES as well as a higher proportion of angiogenic ccrcc2 molecular subtypes (<i>p</i> = 0.008) than primary tumors of patients with non-GM (<i>n</i> = 128). Metastatic lesions in glandular organs (<i>n</i> = 32) also had higher IMmotion Angio (<i>p</i> = 0.008) and JAVELIN Angio (<i>p</i> = 0.02) GES and were more frequently of the ccrcc2 molecular subtype (<i>p</i> = 0.03), compared to metastatic lesions in non-glandular organs in patients who did not develop any GM (<i>n</i> = 231), but not compared to metastatic lesions in non-glandular organs in patients who also developed GM (<i>n</i> = 18). Patients with GM had better OS (HR 0.49, <i>p</i> p = 0.045) than patients with non-GM. PFS on first- or any-line immuno-oncology (IO) was not different. IMmotion Angio, JAVELIN Angio GES, and ccrcc2 molecular subtype were associated with better OS and PFS on first-line VEGFR-TKIs, but not PFS on first or any-line IO. Patients with m-ccRCC who develop GM are molecularly characterized by heightened angiogenesis, translating into better prognosis and better outcomes on VEGFR-TKIs, but not IO. Based on these findings, VEGFR-TKIs should be included in the first-line treatment of m-ccRCC patients with GM.
DOI: 10.6084/m9.figshare.16598565
title: Long term follow-up of frontline Dasatinib in older patients with chronic myeloid leukemia in chronic phase treated outside clinical trials: a real-life cohort observational study

description: A limited amount of data has been published in chronic-phase chronic myeloid leukemia (CP-CML) patients aged &gt;75 years treated frontline with second-generation tyrosine kinase inhibitors. To address this issue in a clinical ‘real-life’ setting, we retrospectively analyzed 45 CP-CML patients (pts) followed in 20 Italian Centers and treated frontline with dasatinib (DAS). Median age was 78.4 years (range 75–89.2 years). DAS starting dose was 100 mg QD in 35 pts (77.7%), 80 mg QD in 1 pts (2.2%) and 50 mg QD in 9 pts (20.1%), respectively. The median follow-up was 42.6 months (IQR 20.4 − 63.3). Grade 3 and 4 side effects, both hematological and non-hematological, were detected in 6 (13.3%) and 12 (26.6%) pts, respectively. Pleural effusions of all grades occurred in 13 pts (28.8%) after a median period of DAS exposure of 14.7 months (IQR 3.0 − 33.1). The rates of DAS dose reduction and permanent drug discontinuation were 53.3% and 20.0%, respectively. As the best response, 42/45 patients (93.3%) achieved a complete cytogenetic response (CCyR), 35/45 (77.7%) a major molecular response (MMR) and 24/45 (53.3%) a deep molecular response (both MR 4.0 and MR 4.5). Only 1 patient (2.2%) progressed to the blast phase after 13 months of therapy; 8 deaths were observed (1 CML-related and 7 CML-unrelated). Cumulative event-free survival and overall survival at 36 months were 64.7% (95%, CI 49.4 − 80.0) and 82.3% (95%, CI 70.3–94.3), respectively. These findings, although evaluated in a limited and selected cohort of patients, suggest that DAS might be effective in older patients (aged &gt;75 years) affected by CP-CML with acceptable toxicity.
DOI: 10.6084/m9.figshare.15060505
title: Target coverage and cardiopulmonary sparing with the updated ESTRO-ACROP contouring guidelines for postmastectomy radiation therapy after breast reconstruction: a treatment planning study using VMAT and proton PBS techniques

description: The European Society for Therapeutic Radiology and Oncology Advisory Committee in Radiation Oncology Practice (ESTRO-ACROP) recently released new contouring guidelines for postmastectomy radiation therapy (PMRT) after implant-based reconstruction (IBR). As compared to prior ESTRO guidelines, the new guidelines primarily redefined the chest wall (CW) target to exclude the breast prosthesis. In this study, we assessed the impact of these changes on treatment planning and dosimetric outcomes using volumetric-modulated arc therapy (VMAT) and proton pencil-beam scanning (PBS) therapy. We performed a treatment planning study of 10 women with left-sided breast cancer who underwent PMRT after IBR. All target structures were delineated first using standard (ESTRO) breast contouring guidelines and then separately using the new (ESTRO-ACROP) guidelines. Standard organs-at-risk (OARs) and cardiac substructures were contoured. Four sets of plans were generated: (1) VMAT using standard ESTRO contours, (2) VMAT using new ESTRO-ACROP contours, (3) PBS using standard contours, and (4) PBS using new contours. VMAT plans using the new ESTRO-ACROP guidelines resulted in modest sparing of the left anterior descending coronary artery (LAD) (mean dose: 6.99 Gy standard ESTRO vs. 6.08 Gy new ESTRO-ACROP, <i>p</i> = 0.010) and ipsilateral lung (V<sub>20</sub>: 21.66% vs 19.45%, <i>p</i> = 0.017), but similar exposure to the heart (mean dose: 4.6 Gy vs. 4.3 Gy, <i>p</i> = 0.513), with a trend toward higher contralateral lung (V<sub>5</sub>: 31.0% vs 35.3%, <i>p</i> = 0.331) and CW doses (V<sub>5</sub>: 31.9% vs 35.4%, <i>p</i> = 0.599). PBS plans using the new guidelines resulted in further sparing of the heart (mean dose: 1.05 Gy(RBE) vs. 0.54 Gy(RBE), <i>p</i> p 20: 16.22% vs 6.02%, <i>p</i> PMRT after IBR using the new ESTRO-ACROP contouring guidelines with both VMAT and PBS therapy is associated with significant changes in exposure to several cardiopulmonary structures.
DOI: 10.6084/m9.figshare.16598565.v1
title: Long term follow-up of frontline Dasatinib in older patients with chronic myeloid leukemia in chronic phase treated outside clinical trials: a real-life cohort observational study

description: A limited amount of data has been published in chronic-phase chronic myeloid leukemia (CP-CML) patients aged &gt;75 years treated frontline with second-generation tyrosine kinase inhibitors. To address this issue in a clinical ‘real-life’ setting, we retrospectively analyzed 45 CP-CML patients (pts) followed in 20 Italian Centers and treated frontline with dasatinib (DAS). Median age was 78.4 years (range 75–89.2 years). DAS starting dose was 100 mg QD in 35 pts (77.7%), 80 mg QD in 1 pts (2.2%) and 50 mg QD in 9 pts (20.1%), respectively. The median follow-up was 42.6 months (IQR 20.4 − 63.3). Grade 3 and 4 side effects, both hematological and non-hematological, were detected in 6 (13.3%) and 12 (26.6%) pts, respectively. Pleural effusions of all grades occurred in 13 pts (28.8%) after a median period of DAS exposure of 14.7 months (IQR 3.0 − 33.1). The rates of DAS dose reduction and permanent drug discontinuation were 53.3% and 20.0%, respectively. As the best response, 42/45 patients (93.3%) achieved a complete cytogenetic response (CCyR), 35/45 (77.7%) a major molecular response (MMR) and 24/45 (53.3%) a deep molecular response (both MR 4.0 and MR 4.5). Only 1 patient (2.2%) progressed to the blast phase after 13 months of therapy; 8 deaths were observed (1 CML-related and 7 CML-unrelated). Cumulative event-free survival and overall survival at 36 months were 64.7% (95%, CI 49.4 − 80.0) and 82.3% (95%, CI 70.3–94.3), respectively. These findings, although evaluated in a limited and selected cohort of patients, suggest that DAS might be effective in older patients (aged &gt;75 years) affected by CP-CML with acceptable toxicity.
DOI: 10.6084/m9.figshare.15152017.v1
title: Evaluation of <sup>18</sup>F-EF5 for detection of hypoxia in localized adenocarcinoma of the prostate

description: A common feature of solid tumours that are resistant to therapy is the presence of regions with low oxygen content (i.e., hypoxia). Oxygen electrode studies suggest that localized prostate adenocarcinoma is commonly hypoxic, although conflicting data have been reported between immunohistochemical detection of hypoxia-induced proteins in biopsy specimens and positron emission tomography (PET) imaging of <sup>18</sup>F-labeled hypoxia reporters. Although the 2-nitroimidazole <sup>18</sup>F-EF5 is well-established to label hypoxic tumour cells in pre-clinical tumour models and clinical trials of multiple primary tumour sites, it has yet to be tested in prostate cancer. The purpose of this study was to evaluate the feasibility of using <sup>18</sup>F-EF5 to detect hypoxia in clinical prostate tumours. Patients with localized adenocarcinoma of the prostate were recruited for pre-treatment <sup>18</sup>F-EF5 PET scans. Immunohistochemistry was conducted on diagnostic biopsies to assess the expression of glucose transporter 1 (GLUT1), osteopontin (OPN), and carbonic anhydrase IX (CAIX). Immunoreactivity scores of staining intensity and frequency were used to indicate the presence of tumour hypoxia. We found low tumour-to-muscle ratios of <sup>18</sup>F-EF5 uptake that were not consistent with tumour hypoxia, causing early termination of the study. However, we observed GLUT1 and OPN expression in all prostate tumour biopsies, indicating the presence of hypoxia in all tumours. Our data do not support the use of <sup>18</sup>F-EF5 PET to detect hypoxia in prostate adenocarcinoma, and suggest the use of immunohistochemistry to quantify expression of the hypoxia-inducible proteins GLUT1 and OPN as indications of prostate tumour hypoxia.
DOI: 10.6084/m9.figshare.15454152.v1
title: The effects of PD-1/PD-L1 checkpoint inhibitors on recurrent/metastatic head and neck squamous cell carcinoma: a critical review of the literature and meta-analysis

description: 50% of patients with locally advanced HNSCC eventually present with disease recurrence or metastasis. Interaction of programmed cell death protein 1 (PD-1) and its ligand, programmed death-ligand 1 (PD-L1), allows tumour cells to evade immune attack by inhibiting T-cell activation. PD-1/PD-L1 checkpoint inhibitors block this immunosuppressive effect. This study aims to investigate the efficacy of anti-PD-1/PD-L1 agents for recurrent/metastatic (R/M) HNSCC in terms of survival, toxicity, and response. It will test the hypothesis that immunotherapy improves treatment outcomes for R/M HNSCC patients. Studies were identified through an electronic search of databases EMBASE and Medline. Data on survival, response and toxicity following PD-1/PD-L1 inhibition was extracted from included studies and compared. A subgroup meta-analysis compared these outcomes in PD-1/PD-L1 inhibition versus the standard of care (SOC). Thirteen studies (<i>n</i> = 1798) were included in this review. Overall survival following PD-1/PD-L1 checkpoint inhibition ranged from 6 to 13 months. The most common treatment-related adverse events (TRAEs) were fatigue, hypothyroidism and nausea; Grade ≥3 TRAEs occurred in 13% of patients. Meta-analysis of RCTs showed that anti-PD-1/PD-L1 agents improved survival and reduced toxicity compared to the SOC. This was demonstrated by a 37% lower risk of death (OR = 0.63, 95% CI = 0.51–0.78, <i>I</i><sup>2</sup> = 18%, <i>p ≤</i> 0.0001) and a 77% lower risk of any-grade TRAEs (OR = 0.23, 95% CI = 0.18–0.29, <i>I</i><sup>2</sup> = 90%, <i>p ≤</i> 0.00001) with immunotherapy versus SOC. Based on the observed safety and efficacy, PD-1/PD-L1 checkpoint inhibition improves treatment outcomes for R/M HNSCC patients. PD-1/PD-L1 inhibitors significantly prolonged survival and reduced toxicity compared to the SOC, however further randomised trials are needed to investigate their role in HNSCC.
DOI: 10.6084/m9.figshare.15454152
title: The effects of PD-1/PD-L1 checkpoint inhibitors on recurrent/metastatic head and neck squamous cell carcinoma: a critical review of the literature and meta-analysis

description: 50% of patients with locally advanced HNSCC eventually present with disease recurrence or metastasis. Interaction of programmed cell death protein 1 (PD-1) and its ligand, programmed death-ligand 1 (PD-L1), allows tumour cells to evade immune attack by inhibiting T-cell activation. PD-1/PD-L1 checkpoint inhibitors block this immunosuppressive effect. This study aims to investigate the efficacy of anti-PD-1/PD-L1 agents for recurrent/metastatic (R/M) HNSCC in terms of survival, toxicity, and response. It will test the hypothesis that immunotherapy improves treatment outcomes for R/M HNSCC patients. Studies were identified through an electronic search of databases EMBASE and Medline. Data on survival, response and toxicity following PD-1/PD-L1 inhibition was extracted from included studies and compared. A subgroup meta-analysis compared these outcomes in PD-1/PD-L1 inhibition versus the standard of care (SOC). Thirteen studies (<i>n</i> = 1798) were included in this review. Overall survival following PD-1/PD-L1 checkpoint inhibition ranged from 6 to 13 months. The most common treatment-related adverse events (TRAEs) were fatigue, hypothyroidism and nausea; Grade ≥3 TRAEs occurred in 13% of patients. Meta-analysis of RCTs showed that anti-PD-1/PD-L1 agents improved survival and reduced toxicity compared to the SOC. This was demonstrated by a 37% lower risk of death (OR = 0.63, 95% CI = 0.51–0.78, <i>I</i><sup>2</sup> = 18%, <i>p ≤</i> 0.0001) and a 77% lower risk of any-grade TRAEs (OR = 0.23, 95% CI = 0.18–0.29, <i>I</i><sup>2</sup> = 90%, <i>p ≤</i> 0.00001) with immunotherapy versus SOC. Based on the observed safety and efficacy, PD-1/PD-L1 checkpoint inhibition improves treatment outcomes for R/M HNSCC patients. PD-1/PD-L1 inhibitors significantly prolonged survival and reduced toxicity compared to the SOC, however further randomised trials are needed to investigate their role in HNSCC.
DOI: 10.6084/m9.figshare.15152017
title: Evaluation of <sup>18</sup>F-EF5 for detection of hypoxia in localized adenocarcinoma of the prostate

description: A common feature of solid tumours that are resistant to therapy is the presence of regions with low oxygen content (i.e., hypoxia). Oxygen electrode studies suggest that localized prostate adenocarcinoma is commonly hypoxic, although conflicting data have been reported between immunohistochemical detection of hypoxia-induced proteins in biopsy specimens and positron emission tomography (PET) imaging of <sup>18</sup>F-labeled hypoxia reporters. Although the 2-nitroimidazole <sup>18</sup>F-EF5 is well-established to label hypoxic tumour cells in pre-clinical tumour models and clinical trials of multiple primary tumour sites, it has yet to be tested in prostate cancer. The purpose of this study was to evaluate the feasibility of using <sup>18</sup>F-EF5 to detect hypoxia in clinical prostate tumours. Patients with localized adenocarcinoma of the prostate were recruited for pre-treatment <sup>18</sup>F-EF5 PET scans. Immunohistochemistry was conducted on diagnostic biopsies to assess the expression of glucose transporter 1 (GLUT1), osteopontin (OPN), and carbonic anhydrase IX (CAIX). Immunoreactivity scores of staining intensity and frequency were used to indicate the presence of tumour hypoxia. We found low tumour-to-muscle ratios of <sup>18</sup>F-EF5 uptake that were not consistent with tumour hypoxia, causing early termination of the study. However, we observed GLUT1 and OPN expression in all prostate tumour biopsies, indicating the presence of hypoxia in all tumours. Our data do not support the use of <sup>18</sup>F-EF5 PET to detect hypoxia in prostate adenocarcinoma, and suggest the use of immunohistochemistry to quantify expression of the hypoxia-inducible proteins GLUT1 and OPN as indications of prostate tumour hypoxia.
DOI: 10.6084/m9.figshare.15131801.v3
title: Distant metastases in squamous cell carcinoma of the pharynx and larynx: a population-based DAHANCA study

description: In head and neck cancer, distant metastases may be present at diagnosis (M1) or occur after treatment (DM). It is unknown whether M1 and DM follow the same clinical development and share prognosis, as population-based studies regarding outcomes are scarce. Therefore, we investigated the incidence, location of metastases and overall survival of patients with M1 and DM. Patients diagnosed with squamous cell carcinoma of the pharynx and larynx in Denmark 2008–2017 were identified in the Danish Head and Neck Cancer Group (DAHANCA) database. We identified 7300 patients, of whom 197 (3%) had M1 and 498 (8%) developed DM during follow-up. The 5-year cumulative incidence of DM was 8%. 1- and 2-year overall survival for DM (27% and 13%) vs. M1 (28% and 9%) were equally poor. There was no significant difference in location of metastases for M1 and DM and the most frequently involved organs were lungs, bone, lymph nodes and liver, in descending order. In oropharyngeal squamous cell carcinomas, the location of metastases did not differ by p16-status. For p16-positive patients, 21% of DM occurred later than three years of follow-up compared to 7% of p16-negative patients. Incidence, location of metastases and prognosis of primary metastatic (M1) or post-treatment metastatic (DM) disease in pharyngeal and laryngeal squamous cell carcinoma are similar in this register-based study
DOI: 10.6084/m9.figshare.16501700.v1
title: Molecular underpinnings of glandular tropism in metastatic clear cell renal cell carcinoma: therapeutic implications

description: Glandular metastases (GM) have been associated with improved survival in metastatic clear cell renal cell carcinoma (m-ccRCC). We aimed to molecularly characterize m-ccRCC with GM. We performed a retrospective cohort study on all m-ccRCC patients with available tissue at our institution, diagnosed with metastatic disease from 2000 to 2019. We determined previously described angiogenesis- and immune-related gene expression signatures (GES) and ccrcc molecular subtypes through whole transcriptome RNA sequencing of primary tumors and metastases. We tested differences in GES and molecular subtypes across groups and studied overall (OS) and progression-free survival (PFS) using Kaplan–Meier survival analysis and Cox regression models. Primary tumors of patients who developed GM (<i>n</i> = 55) had higher IMmotion Angio (<i>p</i> p = 0.003) GES as well as a higher proportion of angiogenic ccrcc2 molecular subtypes (<i>p</i> = 0.008) than primary tumors of patients with non-GM (<i>n</i> = 128). Metastatic lesions in glandular organs (<i>n</i> = 32) also had higher IMmotion Angio (<i>p</i> = 0.008) and JAVELIN Angio (<i>p</i> = 0.02) GES and were more frequently of the ccrcc2 molecular subtype (<i>p</i> = 0.03), compared to metastatic lesions in non-glandular organs in patients who did not develop any GM (<i>n</i> = 231), but not compared to metastatic lesions in non-glandular organs in patients who also developed GM (<i>n</i> = 18). Patients with GM had better OS (HR 0.49, <i>p</i> p = 0.045) than patients with non-GM. PFS on first- or any-line immuno-oncology (IO) was not different. IMmotion Angio, JAVELIN Angio GES, and ccrcc2 molecular subtype were associated with better OS and PFS on first-line VEGFR-TKIs, but not PFS on first or any-line IO. Patients with m-ccRCC who develop GM are molecularly characterized by heightened angiogenesis, translating into better prognosis and better outcomes on VEGFR-TKIs, but not IO. Based on these findings, VEGFR-TKIs should be included in the first-line treatment of m-ccRCC patients with GM.
DOI: 10.5281/zenodo.5595958
title: Plume data

description: Input for numerical simulations, timeseries of estuarine forcing and PTV data.
DOI: 10.5281/zenodo.5595957
title: Plume data

description: Input for numerical simulations, timeseries of estuarine forcing and PTV data.
DOI: 10.6084/m9.figshare.16866286
title: COVID-19 WGS control data - part A

description: SARS-CoV-2 TWIST controls WGS data generated with Oxford Nanopore.
DOI: 10.6084/m9.figshare.16866286.v1
title: COVID-19 WGS control data - part A

description: SARS-CoV-2 TWIST controls WGS data generated with Oxford Nanopore.
DOI: 10.5281/zenodo.5517383
title: Gene Expression (RNA seq)

description: Fastq file used for the bulk RNA-seq analyses in "Disruption of Epithelial Integrity Drives Mesendoderm Differentiation in Human Induced Pluripotent Stem Cells by Enabling BMP and ACTIVIN Sensing", Rattier et al. Preparation and sequencing of RNA was performed by GATC Biotech.
DOI: 10.6084/m9.figshare.12234725
title: Data from: Artificial mosaic brain evolution of relative telencephalon size improves inhibitory control abilities in the guppy (Poecilia reticulata)

description: Mosaic brain evolution, the change in the size of separate brain regions in response to selection on cognition, is an important idea in the field of cognitive evolution. However, till now, most of the data on how separate brain regions respond to selection and their cognitive consequences stem from comparative studies. To experimentally investigate the influence of mosaic brain evolution on cognitive ability, we used male guppies artificially selected for large and small telencephalons relative to the rest of the brain. Here, we tested an important aspect of executive cognitive ability using a detour task. We found that males with larger telencephalons outperformed males with smaller telencephalons. Fish with larger telencephalons showed faster improvement in performance during detour training and were more successful in reaching the food reward without touching the transparent barrier (i.e., through correct detouring) during the test phase. Together, our findings provide the first experimental evidence showing that evolutionary enlargements of relative telencephalon size confer cognitive benefits, supporting an important role for mosaic brain evolution during cognitive evolution.
DOI: 10.26300/xhmw-xt50
title: Textual Data Set of Representations of Violence Against Women in Bangladeshi Newspapers
DOI: 10.6084/m9.figshare.16866229
title: data.xlsx

description: Data from 569 consecutive patients who underwent microsurgical clipping for unruptured PCoA aneurysm between January 2008 and December 2020
DOI: 10.6084/m9.figshare.16866229.v1
title: data.xlsx

description: Data from 569 consecutive patients who underwent microsurgical clipping for unruptured PCoA aneurysm between January 2008 and December 2020