cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.5281/zenodo.5928994
title: Dataset related to article "Mutation profile and immunoscore signature in thymic carcinomas: An exploratory study and review of the literature"

description: This record contains raw data related to article “Mutation profile and immunoscore signature in thymic carcinomas: An exploratory study and review of the literature" <strong>Background: </strong> Significant efforts have been made to investigate the molecular pathways involved in thymic carcinogenesis. However, genetic findings have still not impacted clinical practice. The aim of this exploratory trial was to evaluate the immunoscore and molecular profile of a series of thymic carcinomas (TCs), correlating this data with clinical outcome. <strong>Methods: </strong> Formalin-fixed, paraffin-embedded (FFPE) TC tissues were retrieved from our center archive. The immunoscore was evaluated according to Angell and Gallon. DNA was extracted from FFPE tumor samples and, when available, from adjacent histologically normal tissues. Next-generation sequencing (NGS) was performed targeting hotspot regions of 50 oncogenes and tumor suppressor genes. <strong>Results: </strong> A series of 15 TCs were analyzed. After a median follow-up of 82.4 months, the median overall survival was 104.7 months. The immunoscore was &gt;2 in 5/15 patients (33%). Among the investigated genes, absence of mutations was observed in 5/15 patients (33%), whereas three variants in 1/15 (6%) patient, two variants in 4/15 (26%) patients, and one variant in 5/15 patients (33%) were found. The most recurrently mutated genes were FGFR3 (five mutations) and CDKN2A (three mutations, two of which were nonsense). Patients with CDKN2A loss showed a statistically significantly worse survival (P = 0.0013), whereas patients with FGFR3 mutations showed a statistically significantly better survival (P = 0.048). <strong>Conclusions: </strong> This study adds data to the few existing reports on the mutational landscape of TCs, providing the first comprehensive analysis to date. Here, we confirm the low rate of mutations in TCs and suggest FGFR3 and CDKN2A mutations as intriguing potential therapeutic targets.
DOI: 10.5281/zenodo.5928993
title: Dataset related to article "Mutation profile and immunoscore signature in thymic carcinomas: An exploratory study and review of the literature"

description: This record contains raw data related to article “Mutation profile and immunoscore signature in thymic carcinomas: An exploratory study and review of the literature" <strong>Background: </strong> Significant efforts have been made to investigate the molecular pathways involved in thymic carcinogenesis. However, genetic findings have still not impacted clinical practice. The aim of this exploratory trial was to evaluate the immunoscore and molecular profile of a series of thymic carcinomas (TCs), correlating this data with clinical outcome. <strong>Methods: </strong> Formalin-fixed, paraffin-embedded (FFPE) TC tissues were retrieved from our center archive. The immunoscore was evaluated according to Angell and Gallon. DNA was extracted from FFPE tumor samples and, when available, from adjacent histologically normal tissues. Next-generation sequencing (NGS) was performed targeting hotspot regions of 50 oncogenes and tumor suppressor genes. <strong>Results: </strong> A series of 15 TCs were analyzed. After a median follow-up of 82.4 months, the median overall survival was 104.7 months. The immunoscore was &gt;2 in 5/15 patients (33%). Among the investigated genes, absence of mutations was observed in 5/15 patients (33%), whereas three variants in 1/15 (6%) patient, two variants in 4/15 (26%) patients, and one variant in 5/15 patients (33%) were found. The most recurrently mutated genes were FGFR3 (five mutations) and CDKN2A (three mutations, two of which were nonsense). Patients with CDKN2A loss showed a statistically significantly worse survival (P = 0.0013), whereas patients with FGFR3 mutations showed a statistically significantly better survival (P = 0.048). <strong>Conclusions: </strong> This study adds data to the few existing reports on the mutational landscape of TCs, providing the first comprehensive analysis to date. Here, we confirm the low rate of mutations in TCs and suggest FGFR3 and CDKN2A mutations as intriguing potential therapeutic targets.
DOI: 10.6084/m9.figshare.19096826
title: Kamara GN et al 2022 data

description: Kamara GN et al 2022 data of SORT IT AMR Sierra Leone study (dataset and codebook)
DOI: 10.6084/m9.figshare.19096826.v1
title: Kamara GN et al 2022 data

description: Kamara GN et al 2022 data of SORT IT AMR Sierra Leone study (dataset and codebook)
DOI: 10.5281/zenodo.5929903
title: Dataset related to article "Impact of active cancer on COVID-19 survival: a matchedanalysis on 557 consecutive patients at an Academic Hospital in Lombardy, Italy"

description: This record contains raw data related to article "Impact of active cancer on COVID-19 survival: a matchedanalysis on 557 consecutive patients at an Academic Hospital in Lombardy, Italy" <strong>Background: </strong> The impact of active cancer in COVID-19 patients is poorly defined; however, most studies showed a poorer outcome in cancer patients compared to the general population. <strong>Methods: </strong> We analysed clinical data from 557 consecutive COVID-19 patients. Uni-multivariable analysis was performed to identify prognostic factors of COVID-19 survival; propensity score matching was used to estimate the impact of cancer. <strong>Results: </strong> Of 557 consecutive COVID-19 patients, 46 had active cancer (8%). Comorbidities included diabetes (n = 137, 25%), hypertension (n = 284, 51%), coronary artery disease (n = 114, 20%) and dyslipidaemia (n = 122, 22%). Oncologic patients were older (mean age 71 vs 65, p = 0.012), more often smokers (20% vs 8%, p = 0.009), with higher neutrophil-to-lymphocyte ratio (13.3 vs 8.2, p = 0.046). Fatality rate was 50% (CI 95%: 34.9;65.1) in cancer patients and 20.2% (CI 95%: 16.8;23.9) in the non-oncologic population. Multivariable analysis showed active cancer (HR<sub>active</sub>: 2.26, p = 0.001), age (HR<sub>age&gt;65years</sub>: 1.08, p &lt; 0.001), as well as lactate dehydrogenase (HR<sub>LDH&gt;248mU/mL</sub>: 2.42, p = 0.007), PaO2/FiO2 (HR<sub>continuous</sub>: 1.00, p &lt; 0.001), procalcitonin (HR<sub>PCT&gt;0.5ng/mL</sub>: 2.21, p &lt; 0.001), coronary artery disease (HR<sub>yes</sub>: 1.67, p = 0.010), cigarette smoking (HR<sub>yes</sub>: 1.65, p = 0.041) to be independent statistically significant predictors of outcome. Propensity score matching showed a 1.92× risk of death in active cancer patients compared to non-oncologic patients (p = 0.013), adjusted for ICU-related bias. We observed a median OS of 14 days for cancer patients vs 35 days for other patients. <strong>Conclusion: </strong> A near-doubled death rate between cancer and non-cancer COVID-19 patients was reported. Active cancer has a negative impact on clinical outcome regardless of pre-existing clinical comorbidities.
DOI: 10.5281/zenodo.5929902
title: Dataset related to article "Impact of active cancer on COVID-19 survival: a matchedanalysis on 557 consecutive patients at an Academic Hospital in Lombardy, Italy"

description: This record contains raw data related to article "Impact of active cancer on COVID-19 survival: a matchedanalysis on 557 consecutive patients at an Academic Hospital in Lombardy, Italy" <strong>Background: </strong> The impact of active cancer in COVID-19 patients is poorly defined; however, most studies showed a poorer outcome in cancer patients compared to the general population. <strong>Methods: </strong> We analysed clinical data from 557 consecutive COVID-19 patients. Uni-multivariable analysis was performed to identify prognostic factors of COVID-19 survival; propensity score matching was used to estimate the impact of cancer. <strong>Results: </strong> Of 557 consecutive COVID-19 patients, 46 had active cancer (8%). Comorbidities included diabetes (n = 137, 25%), hypertension (n = 284, 51%), coronary artery disease (n = 114, 20%) and dyslipidaemia (n = 122, 22%). Oncologic patients were older (mean age 71 vs 65, p = 0.012), more often smokers (20% vs 8%, p = 0.009), with higher neutrophil-to-lymphocyte ratio (13.3 vs 8.2, p = 0.046). Fatality rate was 50% (CI 95%: 34.9;65.1) in cancer patients and 20.2% (CI 95%: 16.8;23.9) in the non-oncologic population. Multivariable analysis showed active cancer (HR<sub>active</sub>: 2.26, p = 0.001), age (HR<sub>age&gt;65years</sub>: 1.08, p &lt; 0.001), as well as lactate dehydrogenase (HR<sub>LDH&gt;248mU/mL</sub>: 2.42, p = 0.007), PaO2/FiO2 (HR<sub>continuous</sub>: 1.00, p &lt; 0.001), procalcitonin (HR<sub>PCT&gt;0.5ng/mL</sub>: 2.21, p &lt; 0.001), coronary artery disease (HR<sub>yes</sub>: 1.67, p = 0.010), cigarette smoking (HR<sub>yes</sub>: 1.65, p = 0.041) to be independent statistically significant predictors of outcome. Propensity score matching showed a 1.92× risk of death in active cancer patients compared to non-oncologic patients (p = 0.013), adjusted for ICU-related bias. We observed a median OS of 14 days for cancer patients vs 35 days for other patients. <strong>Conclusion: </strong> A near-doubled death rate between cancer and non-cancer COVID-19 patients was reported. Active cancer has a negative impact on clinical outcome regardless of pre-existing clinical comorbidities.
DOI: 10.6084/m9.figshare.13536259.v2
title: Dynamic changes in DNA methylation occur in TE regions and affect cell proliferation during leaf-to-callus transition in Arabidopsis

description: Plant somatic cells can be reprogrammed into pluripotent cell mass, called callus, through a two-step <i>in vitro</i> tissue culture method. Incubation on callus-inducing medium triggers active cell proliferation to form a pluripotent callus. Notably, DNA methylation is implicated during callus formation, but a detailed molecular process regulated by DNA methylation remains to be fully elucidated. Here, we compared genome-wide DNA methylation profiles between leaf and callus tissues in <i>Arabidopsis</i> using whole-genome bisulphite-sequencing. Global distribution of DNA methylation showed that CHG methylation was increased, whereas CHH methylation was reduced especially around transposable element (TE) regions during the leaf-to-callus transition. We further analysed differentially expressed genes around differentially methylated TEs (DMTEs) during the leaf-to-callus transition and found that genes involved in cell cycle regulation were enriched and also constituted a coexpression gene network along with pluripotency regulators. In addition, a conserved DNA sequence analysis for upstream <i>cis</i>-elements led us to find a putative transcription factor associated with cell fate transition. CIRCADIAN CLOCK-ASSOCIATED 1 (CCA1) was newly identified as a regulator of plant regeneration, and consistently, the <i>cca1lhy</i> mutant displayed altered phenotypes in callus proliferation. Overall, these results suggest that DNA methylation coordinates cell cycle regulation during callus formation, and CCA1 may act as a key upstream coordinator at least in part in the processes.
DOI: 10.6084/m9.figshare.17308517
title: Generalized Good-Turing Improves Missing Mass Estimation

description: Consider a finite sample from an unknown distribution over a countable alphabet. The missing mass refers to the probability of symbols that do not appear in the sample. Estimating the missing mass is a basic problem in statistics and related fields, which dates back to the early work of Laplace, and the more recent seminal contribution of Good and Turing. In this article, we introduce a generalized Good-Turing (GT) framework for missing mass estimation. We derive an upper-bound for the risk (in terms of mean squared error) and minimize it over the parameters of our framework. Our analysis distinguishes between two setups, depending on the (unknown) alphabet size. When the alphabet size is bounded from above, our risk-bound demonstrates a significant improvement compared to currently known results (which are typically oblivious to the alphabet size). Based on this bound, we introduce a numerically obtained estimator that improves upon GT. When the alphabet size holds no restrictions, we apply our suggested risk-bound and introduce a closed-form estimator that again improves GT performance guarantees. Our suggested framework is easy to apply and does not require additional modeling assumptions. This makes it a favorable choice for practical applications. Supplementary materials for this article are available online.
DOI: 10.6084/m9.figshare.17308517.v1
title: Generalized Good-Turing Improves Missing Mass Estimation

description: Consider a finite sample from an unknown distribution over a countable alphabet. The missing mass refers to the probability of symbols that do not appear in the sample. Estimating the missing mass is a basic problem in statistics and related fields, which dates back to the early work of Laplace, and the more recent seminal contribution of Good and Turing. In this article, we introduce a generalized Good-Turing (GT) framework for missing mass estimation. We derive an upper-bound for the risk (in terms of mean squared error) and minimize it over the parameters of our framework. Our analysis distinguishes between two setups, depending on the (unknown) alphabet size. When the alphabet size is bounded from above, our risk-bound demonstrates a significant improvement compared to currently known results (which are typically oblivious to the alphabet size). Based on this bound, we introduce a numerically obtained estimator that improves upon GT. When the alphabet size holds no restrictions, we apply our suggested risk-bound and introduce a closed-form estimator that again improves GT performance guarantees. Our suggested framework is easy to apply and does not require additional modeling assumptions. This makes it a favorable choice for practical applications. Supplementary materials for this article are available online.
DOI: 10.6084/m9.figshare.13673466
title: Radiation-induced cardiovascular disease: an overlooked role for DNA methylation?

description: Radiotherapy in cancer treatment involves the use of ionizing radiation for cancer cell killing. Although radiotherapy has shown significant improvements on cancer recurrence and mortality, several radiation-induced adverse effects have been documented. Of these adverse effects, radiation-induced cardiovascular disease (CVD) is particularly prominent among patients receiving mediastinal radiotherapy, such as breast cancer and Hodgkin’s lymphoma patients. A number of mechanisms of radiation-induced CVD pathogenesis have been proposed such as endothelial inflammatory activation, premature endothelial senescence, increased ROS and mitochondrial dysfunction. However, current research seems to point to a so-far unexamined and potentially novel involvement of epigenetics in radiation-induced CVD pathogenesis. Firstly, epigenetic mechanisms have been implicated in CVD pathophysiology. In addition, several studies have shown that ionizing radiation can cause epigenetic modifications, especially DNA methylation alterations. As a result, this review aims to provide a summary of the current literature linking DNA methylation to radiation-induced CVD and thereby explore DNA methylation as a possible contributor to radiation-induced CVD pathogenesis.
DOI: 10.6084/m9.figshare.13673466.v1
title: Radiation-induced cardiovascular disease: an overlooked role for DNA methylation?

description: Radiotherapy in cancer treatment involves the use of ionizing radiation for cancer cell killing. Although radiotherapy has shown significant improvements on cancer recurrence and mortality, several radiation-induced adverse effects have been documented. Of these adverse effects, radiation-induced cardiovascular disease (CVD) is particularly prominent among patients receiving mediastinal radiotherapy, such as breast cancer and Hodgkin’s lymphoma patients. A number of mechanisms of radiation-induced CVD pathogenesis have been proposed such as endothelial inflammatory activation, premature endothelial senescence, increased ROS and mitochondrial dysfunction. However, current research seems to point to a so-far unexamined and potentially novel involvement of epigenetics in radiation-induced CVD pathogenesis. Firstly, epigenetic mechanisms have been implicated in CVD pathophysiology. In addition, several studies have shown that ionizing radiation can cause epigenetic modifications, especially DNA methylation alterations. As a result, this review aims to provide a summary of the current literature linking DNA methylation to radiation-induced CVD and thereby explore DNA methylation as a possible contributor to radiation-induced CVD pathogenesis.
DOI: 10.6084/m9.figshare.13536259.v1
title: Dynamic changes in DNA methylation occur in TE regions and affect cell proliferation during leaf-to-callus transition in <i>Arabidopsis</i>

description: Plant somatic cells can be reprogrammed into pluripotent cell mass, called callus, through a two-step <i>in vitro</i> tissue culture method. Incubation on callus-inducing medium triggers active cell proliferation to form pluripotent callus. Notably, DNA methylation is implicated during callus formation, but a detailed molecular process regulated by DNA methylation remains to be fully elucidated. Here, we compared genome-wide DNA methylation profiles between leaf and callus tissues in <i>Arabidopsis</i> using whole genome bisulfite-sequencing. Global distribution of DNA methylation showed that CHG methylation was increased, whereas CHH methylation was reduced especially around transposable element (TE) regions during leaf-to-callus transition. We further analyzed differentially expressed genes around differentially methylated TEs (DMTEs) during leaf-to-callus transition and found that genes involved in cell cycle regulation were enriched and also constituted a coexpression gene network along with pluripotency regulators. In addition, a conserved DNA sequence analysis for upstream <i>cis</i>-elements led us to find a putative transcription factor associated with cell fate transition. CIRCADIAN CLOCK-ASSOCIATED 1 (CCA1) was newly identified as a regulator of plant regeneration, and consistently, the <i>cca1lhy</i> mutant displayed altered phenotypes in callus proliferation. Overall, these results suggest that DNA methylation coordinates cell cycle regulation during callus formation, and CCA1 may act as a key upstream coordinator at least in part in the processes.
DOI: 10.6084/m9.figshare.13637083
title: Differential regulation of <i>LRRC37A2</i> in gastric cancer by DNA methylation

description: Gastric cancer (GC) is one of the leading types of fatal cancer worldwide. Epigenetic manipulation of cancer cells is a useful tool to better understand gene expression regulatory mechanisms and contributes to the discovery of novel biomarkers. Our research group recently reported a list of 83 genes that are potentially modulated by DNA methylation in GC cell lines. Herein, we further explored the regulation of one of these genes, <i>LRRC37A2</i>, in clinical samples. <i>LRRC37A2</i> expression was evaluated by RT-qPCR, and DNA methylation was studied using next-generation bisulphite sequencing in 36 GC and paired adjacent nonneoplastic tissue samples. We showed that both reduced <i>LRRC37A2</i> mRNA levels and increased <i>LRRC37A2</i> exon methylation were associated with undifferentiated and poorly differentiated tumours. Moreover, <i>LRRC37A2</i> gene expression and methylation levels were inversely correlated at the +45 exon CpG site. We suggest that DNA hypermethylation may contribute to reducing <i>LRRC37A2</i> expression in undifferentiated and poorly differentiated GC. Therefore, our results show how some genes may be useful to stratify patients who are more likely to benefit from epigenetic therapy.<b>Abbreviations:</b> AR: androgen receptor; 5-AZAdC: 5-aza-2'-deoxycytidine; <i>B2M</i>: beta-2-microglobulin; <i>GAPDH</i>: glyceraldehyde-3-phosphate dehydrogenase; GC: gastric cancer; GLM: general linear model; <i>LRRC37A2</i>: leucine-rich repeat containing 37 member A2; SD: standard deviation; TFII-I: general transcription factor II-I; TSS: transcription start site; XBP1: X-box binding protein 1
DOI: 10.6084/m9.figshare.13637083.v1
title: Differential regulation of <i>LRRC37A2</i> in gastric cancer by DNA methylation

description: Gastric cancer (GC) is one of the leading types of fatal cancer worldwide. Epigenetic manipulation of cancer cells is a useful tool to better understand gene expression regulatory mechanisms and contributes to the discovery of novel biomarkers. Our research group recently reported a list of 83 genes that are potentially modulated by DNA methylation in GC cell lines. Herein, we further explored the regulation of one of these genes, <i>LRRC37A2</i>, in clinical samples. <i>LRRC37A2</i> expression was evaluated by RT-qPCR, and DNA methylation was studied using next-generation bisulphite sequencing in 36 GC and paired adjacent nonneoplastic tissue samples. We showed that both reduced <i>LRRC37A2</i> mRNA levels and increased <i>LRRC37A2</i> exon methylation were associated with undifferentiated and poorly differentiated tumours. Moreover, <i>LRRC37A2</i> gene expression and methylation levels were inversely correlated at the +45 exon CpG site. We suggest that DNA hypermethylation may contribute to reducing <i>LRRC37A2</i> expression in undifferentiated and poorly differentiated GC. Therefore, our results show how some genes may be useful to stratify patients who are more likely to benefit from epigenetic therapy.<b>Abbreviations:</b> AR: androgen receptor; 5-AZAdC: 5-aza-2'-deoxycytidine; <i>B2M</i>: beta-2-microglobulin; <i>GAPDH</i>: glyceraldehyde-3-phosphate dehydrogenase; GC: gastric cancer; GLM: general linear model; <i>LRRC37A2</i>: leucine-rich repeat containing 37 member A2; SD: standard deviation; TFII-I: general transcription factor II-I; TSS: transcription start site; XBP1: X-box binding protein 1
DOI: 10.6084/m9.figshare.13536259
title: Dynamic changes in DNA methylation occur in TE regions and affect cell proliferation during leaf-to-callus transition in Arabidopsis

description: Plant somatic cells can be reprogrammed into pluripotent cell mass, called callus, through a two-step <i>in vitro</i> tissue culture method. Incubation on callus-inducing medium triggers active cell proliferation to form a pluripotent callus. Notably, DNA methylation is implicated during callus formation, but a detailed molecular process regulated by DNA methylation remains to be fully elucidated. Here, we compared genome-wide DNA methylation profiles between leaf and callus tissues in <i>Arabidopsis</i> using whole-genome bisulphite-sequencing. Global distribution of DNA methylation showed that CHG methylation was increased, whereas CHH methylation was reduced especially around transposable element (TE) regions during the leaf-to-callus transition. We further analysed differentially expressed genes around differentially methylated TEs (DMTEs) during the leaf-to-callus transition and found that genes involved in cell cycle regulation were enriched and also constituted a coexpression gene network along with pluripotency regulators. In addition, a conserved DNA sequence analysis for upstream <i>cis</i>-elements led us to find a putative transcription factor associated with cell fate transition. CIRCADIAN CLOCK-ASSOCIATED 1 (CCA1) was newly identified as a regulator of plant regeneration, and consistently, the <i>cca1lhy</i> mutant displayed altered phenotypes in callus proliferation. Overall, these results suggest that DNA methylation coordinates cell cycle regulation during callus formation, and CCA1 may act as a key upstream coordinator at least in part in the processes.
DOI: 10.6084/m9.figshare.18624224
title: Hemisensory loss after ventriculoperitoneal shunt insertion: Case Report

description: We describe a case which developed hemisensory loss after ventriculoperitoneal shunt insertion.