bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract B68: Spatial and temporal conditions for Smarcb1 deletion determines mouse AT/RT (atypical teratoid/rhabdoid tumor) subtype
Authors: Han Zhi-Yan , Andrianteranagna Mamy , Jesus-Lobon-Iglesias Maria , Tauziède-Espariat Arnault , Beccaria Kevin , Fréneaux Paul , Waterfall Joshua J. , Masliah-Planchon Julien , Bourneix Christine , Pierron Gaelle , Leruste Amaury , Chauvin Céline , Surdez Didier , Varlet Pascale , Dufour Christelle , Delattre Olivier , Dangouloff-Ros Volodia , Bourdeaut Franck 
Published: August 2020

Abstract
The cell(s) of origin of AT/RTs remain(s) unknown. We previously developed a mouse model consisting of tamoxifen inducible system in a Smarcb1Flox/Flox;Rosa26-CreERT2 background. We obtained two molecular subgroups of intracranial tumors, one with neuronal and the other with non-neuronal features, consistent with the diversity observed in human AT/RTs. To investigate the potential cell(s) of origin of these various AT/RTs, we first explored whether different time points of Smarcb1 inactivation correlated with anatomic location and/or molecular subgroups. We observed that the neuronal group, primarily developing from the subventricular zone and the spinal cord, was almost exclusively obtained with the earliest inactivation time points (E6-E7). In contrast, the non-neuronal group emerged upon Smarcb1 inactivation at any time point (E6-E10) and showed intracranial but extra-parenchymal/meningeal origins. High-resolution analysis of anatomic distribution of 55 human AT/RT and molecular subgroups is in progress. In order to more specifically identify the cell(s) of origin for the neuronal group, we next generated developmental stage-specific conditional knockout mice carrying Smarcb1 inactivation by restricting Cre expression with promoters characteristic for various neural stem cells/progenitors. While Smarcb1Flox/Flox;Atoh1CreERT2 showed ataxia but failed to give rise to any tumor at any embryonal time point, Smarcb1Flox/Flox;Ascl1CreERT2 did not show any phenotype. Targeting Nestin-expressing cells led to tumors with morphologic rhabdoid features; these tumors again showed molecular diversity as observed in human AT/RTs. In conclusion, we show that deletion of Smarcb1 determines mouse AT/RT subtypes depending on spatial and temporal factors. Our new mouse models not only give insight into the cell(s) of origin, but also provide interesting preclinical models of AT/RTs.
Citation Format: Zhi-Yan Han, Mamy Andrianteranagna, Maria Jesus-Lobon-Iglesias, Arnault Tauziède-Espariat, Kevin Beccaria, Paul Fréneaux, Joshua J. Waterfall, Julien Masliah-Planchon, Christine Bourneix, Gaelle Pierron, Amaury Leruste, Céline Chauvin, Didier Surdez, Pascale Varlet, Christelle Dufour, Olivier Delattre, Volodia Dangouloff-Ros, Franck Bourdeaut. Spatial and temporal conditions for Smarcb1 deletion determines mouse AT/RT (atypical teratoid/rhabdoid tumor) subtype [abstract]. In: Proceedings of the AACR Special Conference on the Advances in Pediatric Cancer Research; 2019 Sep 17-20; Montreal, QC, Canada. Philadelphia (PA): AACR; Cancer Res 2020;80(14 Suppl):Abstract nr B68.
Abstract IA02: Novel strategies for early cancer detection and prevention: The Li-Fraumeni syndrome story
Authors: Malkin David , Light Nicholas , Subrasi Valli , Brew Benjamin , Paramathas Sangeetha , Nabbi Arash , Prykhozhij Sergei , Pugh Trevor , Berman Jason , Goldenberg Anna , Shlien Adam 
Published: August 2020

Abstract
More than 85% of patients with Li-Fraumeni syndrome harbor germline TP53 mutations. The spectrum of mutations and the heterogeneity of tumor presentation (age of onset and type) within and between families is remarkable and indicates that modifiers must play an important role in defining the phenotype of each patient and each family. We recently reported the feasibility and utility of a clinical surveillance protocol for early detection of tumors in TP53 mutation carriers (Villani et al., Lancet Oncol 2016). Results from deep sequencing of the genome and epigenome of germline and tumor tissues of TP53 mutation carriers provide exciting new insight into the role of modifiers on both the functional activity of p53 in the germline as well as their influence on tumor onset, tumor spectrum, and clinical outcome/response to therapy. Data will be presented to support the creation of molecular algorithms that may be used in a precise manner to predict cancer onset, as well as to better define the molecular landscape of cancers that arise in TP53 mutation carriers. It is anticipated that the combined use of this germline and somatic landscape data can more effectively refine and guide the creation of personalized surveillance and chemoprevention strategies for these patients.
Citation Format: David Malkin, Nicholas Light, Valli Subrasi, Benjamin Brew, Sangeetha Paramathas, Arash Nabbi, Sergei Prykhozhij, Trevor Pugh, Jason Berman, Anna Goldenberg, Adam Shlien. Novel strategies for early cancer detection and prevention: The Li-Fraumeni syndrome story [abstract]. In: Proceedings of the AACR Special Conference on the Advances in Pediatric Cancer Research; 2019 Sep 17-20; Montreal, QC, Canada. Philadelphia (PA): AACR; Cancer Res 2020;80(14 Suppl):Abstract nr IA02.
Abstract IA10: Activating innate and adaptive immunity to improve outcome for “cold” tumors
Authors: Sondel Paul M. 
Published: August 2020

Abstract
Unlike some adult cancers, most pediatric cancers are considered immunologically cold and generally less responsive to immunotherapy. Anti-GD2 mAb plus cytokine-based immunotherapy has already been incorporated into standard-of-care treatment for pediatric patients with high-risk neuroblastoma achieving remission. However, overall survival remains poor. We are pursuing clinical and preclinical studies to engage innate and adaptive immune responses against immunologically cold tumors. In a recent trial of adjuvant/neoadjuvant anti-GD2 mAb + IL2 (in the form of the hu14.18-IL2 immunocytokine) for advanced resectable melanoma, we evaluated whole-genome transcriptomics (using RNAseq determined immunologic signatures found to be predictive of outcome for patients with neuroblastoma) on resected tumors. The immunologic signatures were highly correlated with overall survival and relapse-free survival for tumors obtained 2 weeks after starting hu14.18-IL2, but not for tumors obtained 2 weeks before starting hu14.18-IL2. In a “functionally cold” mouse melanoma model, we found that radiation and hu14.18-IL2 immunocytokine generate an in situ vaccination-induced adaptive immune response in syngeneic mice bearing large tumors. In contrast, this same approach was not effective in mice bearing a very cold, low-tumor-mutation burden, MYCN driven syngeneic neuroblastoma (9464D-GD2). The addition of checkpoint blockade (IgG2a anti-CTLA-4) was not able to induce tumor eradication. However, the further addition of CpG (as a “danger signal”) and agonist anti-CD40 mAb (as an activator of effector macrophages and of dendritic cells) resulted in tumor-free mice with immune memory. These results suggest that immune activation, with “off the shelf” reagents, may be applicable to the treatment of cold cancers, via innate/adaptive immune engagement. They also suggest that monitoring of intratumoral immune activation could potentially become a useful predictor of which patients will respond to their therapy and which will require additional or alternate therapy.
Citation Format: Paul M. Sondel. Activating innate and adaptive immunity to improve outcome for “cold” tumors [abstract]. In: Proceedings of the AACR Special Conference on the Advances in Pediatric Cancer Research; 2019 Sep 17-20; Montreal, QC, Canada. Philadelphia (PA): AACR; Cancer Res 2020;80(14 Suppl):Abstract nr IA10.
Abstract IA16: Accelerating innovation for children with cancer in the new regulatory environment
Authors: Vassal Gilles 
Published: August 2020

Abstract
Over the last 20 years, several pieces of regulation have been launched, in the US and in Europe, to mandate and incentivize the development of safe and effective medicines for children. It has been a success in several pediatric specialties such as rheumatology, infection diseases, cardiovascular diseases, allergy, and several rare pediatric diseases. In oncology, the landscape of pediatric drug development has significantly changed, but very few new anticancer medicines have been approved for the treatment of pediatric malignancies over the last 10 years as compared to the high number of anticancer drugs approved for the treatment of cancer in adults: dinutuximab for neuroblastoma, blinatumomab and tisagenlecleucel for acute lymphoblastic leukemia, and larotrectinib for NTRK positive malignancies. So far, the regulations mandated the pediatric development of any drug if the indicated disease in adults occurred in children. If not, a waiver was issued and the company did not have to study the drug in children. In oncology, malignancies in children and in adults are different, but the same drugs are used to treat both, and often the same biologic alterations (targets) are found in both adult and pediatric malignancies. Too many oncology drugs have been waived. In addition, the pediatric trials of oncology products as part of Pediatric Investigation Plans and Pediatric Study Plans started late in the life cycle of product development and often close to or after the marketing authorization. There is a crucial need to improve and accelerate new drug development for children and adolescents with cancer. The goal is to drive pediatric oncology drug developments through science (using biology, preclinical evaluation, and precision medicine), to better meet patients’ unmet medical needs and to facilitate prioritization among all compounds in development. The FDA Race for Children Act is setting a new regulatory environment that will improve the situation by asking pediatric development of oncology products if their target is “directed at a molecular target that the Secretary determines to be substantially relevant to the growth or progression of a pediatric cancer.” In addition, over the last 5 years, the value of having all stakeholders, i.e. academia, parents, industry and regulators, working together has been demonstrated by ACCELERATE, the international multistakeholder platform (www.accelerate-platform.org). Accelerating innovation for pediatric cancers is urgently needed and feasible in the new regulatory environment and requires international cooperation of all stakeholders.
Citation Format: Gilles Vassal. Accelerating innovation for children with cancer in the new regulatory environment [abstract]. In: Proceedings of the AACR Special Conference on the Advances in Pediatric Cancer Research; 2019 Sep 17-20; Montreal, QC, Canada. Philadelphia (PA): AACR; Cancer Res 2020;80(14 Suppl):Abstract nr IA16.
Abstract PR16: Comprehensive transcriptomic characterization of 1,400 sarcomas for diagnosis and immune contexture
Authors: Vibert Julien , Watson Sarah , Benoist Camille , Waterfall Joshua , Pierron Gaëlle , Delattre Olivier 
Published: August 2020

Abstract
Introduction: Sarcomas represent about 15 % of all childhood cancers and are still lethal in a large proportion of cases. They comprise a heterogeneous group of bone and soft tissue tumors with more than 100 distinct histologic entities, often presenting a diagnostic challenge to pathologists.
Methods: To address this pathological complexity and better characterize the molecular biology of sarcomas, we performed whole-transcriptome RNA-seq on frozen tumor tissues as part of the diagnostic workflow for more than 1,400 patients, mainly children and young adults, addressed for sarcoma molecular diagnosis throughout France.
Results: From a clinical perspective, RNA-seq proves to be a powerful complementary test to pathology for diagnosis of sarcomas: it allows agnostic detection of subtype-specific fusion transcripts, as well as diagnostic indication by gene-expression profile clustering. In addition to its diagnostic utility, RNA-seq provides a rich source of information for studying the molecular biology of sarcomas. Indeed, as shown recently in our group, it allows detection of previously uncharacterized sarcoma entities associated with novel fusion genes. Using dimensionality reduction techniques, either linear such as PCA, or nonlinear such as t-SNE or UMAP, we perform unsupervised clustering of our cohort, revealing insights into the global structure of the transcriptomic landscape of sarcomas. We show that many histologic entities have a distinct gene-expression profile, emphasizing the utility of RNA-seq for diagnosis. To explore the immune microenvironment of sarcomas and potential correlates of response to immunotherapy, we deconvolute bulk RNA-seq data to estimate the presence of immune and stromal cell types, allowing a comprehensive characterization of the immune landscape of sarcomas. Finally, we apply state-of-the-art deep learning tools to perform unsupervised clustering and nonlinear dimensional reduction of our RNA-seq samples, allowing a finer and more insightful representation of the structure of the sarcoma transcriptomic landscape.
Conclusion: Besides improving the diagnostic workflow for patients, our comprehensive analysis of sarcoma RNA-seq allows characterization of distinct molecular subtypes and of the immune landscape, opening up perspectives for better diagnosis, classification, and biologic discoveries in sarcoma.
This abstract is also being presented as Poster B75.
Citation Format: Julien Vibert, Sarah Watson, Camille Benoist, Joshua Waterfall, Gaëlle Pierron, Olivier Delattre. Comprehensive transcriptomic characterization of 1,400 sarcomas for diagnosis and immune contexture [abstract]. In: Proceedings of the AACR Special Conference on the Advances in Pediatric Cancer Research; 2019 Sep 17-20; Montreal, QC, Canada. Philadelphia (PA): AACR; Cancer Res 2020;80(14 Suppl):Abstract nr PR16.
<p><strong><em>Begonia beijnenii </em></strong><strong>(Begoniaceae, section <em>Baryandra</em>), a new species of <em>Begonia</em> from San Vicente, Palawan, the Philippines</strong></p>
Authors: ANG YU PIN , TANDANG DANILO N. , RUBITE ROSARIO R. , BUSTAMANTE RENE ALFRED ANTON 
Published: August 2020

In our study, a distinctive new species of Begonia from an unexplored region of Port Barton, San Vicente, Palawan, B. beijnenii, is described and illustrated. The new species belongs to section Baryandra. It is morphologically most similar to B. hughesii, in having a 3-winged ovary with a cucullate wing and an abortive abaxial locule, tomentose petioles, and leaves that are adaxially glabrous and abaxially subglabrous. However, B. beijnenii distinctly differs by being comparatively smaller in size. It is only known from its type locality and vicinity. Comparisons with two variegated species of Palawan: B. cleopatrae and B. gironellae are also provided to aid in identification. B. beijnenii is hereby proposed to be Vulnerable (VU) D1, based on guidelines by IUCN.
Subseasonal Forecasts of Tropical Cyclones in the Southern Hemisphere Using a Dynamical Multimodel Ensemble
Authors: Gregory Paul , Vitart Frederic , Rivett Rabi , Brown Andrew , Kuleshov Yuriy 
Published: August 2020

AbstractSubseasonal tropical cyclone forecasts from two operational forecast models are verified for the 2017/18 and 2018/19 Southern Hemisphere cyclone seasons. The forecasts are generated using the ECMWF’s Medium- and Extended-Range Ensemble Integrated Forecasting System (IFS), and the Bureau of Meteorology’s seasonal forecasting system ACCESS-S1. Results show the IFS is more skillful than ACCESS-S1, which is attributed to the IFS’s greater ensemble size, increased spatial resolution, and data assimilation schemes. Applying a lagged ensemble with ACCESS-S1 increases forecast reliability, with the optimum number of lagged members being dependent on forecast lead time. To investigate the impacts of atmospheric assimilation at shorter lead times, comparisons were made between the Bureau of Meteorology’s ACCESS-S1 and ACCESS-GE2 systems, the latter a global Numerical Weather Prediction system running with the same resolution and model physics as ACCESS-S1 but using an ensemble Kalman filter for data assimilation. This comparison showed the data assimilation scheme used in the GE2 system gave improvements in forecast skill for days 8–10, despite the smaller ensemble size used in GE2 (24 members per forecast compared to 33). Finally, a multimodel ensemble was created by combining forecasts from both the IFS and ACCESS-S1. Using the multimodel ensemble gave improvements in forecast skill and reliability. This improvement is attributed to complementary spatial errors in both systems occurring across much of the Southern Hemisphere as well as an increase in the ensemble size.
Research Note: Governance Indicators Explain Discrepancies in COVID‐19 Data
Authors: Baris Omer F. , Pelizzo Riccardo 
Published: August 2020

The severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) is neutral. It does not discriminate: the outbreak affects all countries. Yet, countries with better governance detect and report COVID‐19 cases an average of 34 days earlier than countries with low governance scores. They also report a significantly higher number of cases, and more deaths but lower death‐per‐case ratios. Analyzing the statistical relationship between the good governance indicators devised by the World Bank with data pertaining to COVID‐19 (to May 10, 2020), we present some initial yet strong statistical evidence that countries with higher levels of good governance based on the Worldwide Governance Indicators report more (cases, deaths), report earlier, and are more effective at reducing fatalities. These findings remain robust after controlling for population size, population density, old‐age population, and the number of tourist arrivals. Countries with better governance are more successful in treating the disease and in reducing its deadliness. Good governance matters.
The Quality of Life in Bipolar Disorder (QoL.BD) Scale: Validation of a French Cross-Cultural Adaptation
Authors: Provencher Martin D. , Morton Emma , Beaudoin Anne Sophie , Guillemette Judith , Rheault Evelyne , Mérette Chantal , Coque Laurent , Hawke Lisa D. , Michalak Erin E. 
Published: August 2020

Objective: The goal of this study was to validate the French version of the Quality of Life in Bipolar Disorder (QoL.BD) scale, a condition-specific measure for bipolar disorder (BD). Method: The QoL.BD scale was translated into French in accordance with the recommendations for transcultural adaptation. It was administered to 125 participants with BD living in Quebec, Canada. Construct validity was evaluated through correlations with other measures of self-reported quality of life (QoL), functioning, and symptoms. Factorial structure was examined through an exploratory factor analysis. Results: Internal reliability and test–retest reliability standards were met. Correlations in expected directions with other QoL, functioning, and depressive symptom scales supported convergent validity. The item loadings structure of the French QoL.BD largely replicated the original English version, with some modifications. Conclusion: The French version of the QoL.BD (full and brief) is comparable in its psychometric properties to the English version. It is a valid and sound measure for the evaluation of the QoL of French-speaking patients with BD.
Assessment of serum glucose/potassium ratio as a predictor for delayed neuropsychiatric syndrome of carbon monoxide poisoning
Authors: Demirtaş E , Korkmaz İ , Tekin YK , Demirtaş Es , Çaltekin İ 
Published: August 2020

Introduction: Carbon monoxide (CO) poisoning is a crucial cause of delayed neuropsychiatric syndrome (DNS). However, most biomarkers are not satisfactory for the prediction of DNS caused by CO poisoning. Thus, we evaluated the adequacy of the serum glucose/potassium (GLU/K) ratio, which may be an easy, quick, and readily available parameter that can be used in the emergency department for predicting DNS. Methods: We evaluated 281 patients who were admitted to our emergency department between January 2012 and December 2018. The patients were divided into two groups: DNS (+) and DNS (−). The GLU/K was compared for the groups. Results: Glucose, blood urea nitrogen, carboxyhemoglobin, and GLU/K ratios of patients in the DNS (+) group were statistically significantly higher than those patients in DNS (−) group (140 ± 34 vs. 110 ± 24, p < 0.001; 17.58 ± 6.14 vs. 14.27 ± 5.08, p = 0.003; 29 ± 5.1 vs. 18.9 ± 7.6, p < 0.001; and 38.35 ± 10.11 vs. 28.65 ± 6.53, p < 0.001, respectively). The area under the curve for GLU/K to predict DNS was measured as 0.791, and 35.9 as a cut-off value had 63.6% sensitivity and 89.6% specificity. Conclusions: DNS development in CO poisoning is a serious and feared complication. We suggest that the GLU/K ratio has a high potential as a rapid, easy preliminary marker for the exclusion of patients who will not subsequently develop DNS.
Change in Initial Tympanostomy Tube Placement Timing Yields Decreased Burden of Care Without Increased Complications in Patients With Cleft Lip and Palate
Authors: Davis William , Cohen Marilyn A. , Matthews Martha S. 
Published: August 2020

Objective: To report a practice audit of the consequences of a change in protocol in the timing of placement of tympanostomy tubes in infants with cleft lip and palate. Participants: All children with a diagnosis of cleft lip and palate, treated between November 1998 and May 2006 under the old protocol, and between December 2012 and July 2016 under a new protocol. Under the old protocol, tympanostomy tubes were first inserted at the time of lip repair at around age 2 months. Under the new protocol, tympanostomy tubes were deferred until the time of palate repair around the age of 9 months. Children with syndromic diagnoses other than Stickler syndrome and Van der Woude syndrome, and children who failed newborn hearing screen were excluded. Main Outcome Measures: Incidence of otorrhea from birth to 6 months after palate repair and presence of hearing loss at ages 1 and 2. Results: Deferral of tympanostomy tubes until the time of palate repair decreases the burden of care due to otorrhea as compared to early tympanostomy tubes at the time of lip repair. There was no significant difference in the incidence of hearing thresholds at or below 15 dB at age 1 or 2. Conclusions: Placement of tympanostomy tubes at the time of palate repair balances the goals of minimizing the adverse effects from middle ear effusion and minimizing the burden of care on our patients and their families.