bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prevalence of germline GATA2 and SAMD9/9L variants in paediatric haematological disorders with monosomy 7
Authors: Yoshida Masanori , Tanase‐Nakao Kanako , Shima Hirohito , Shirai Ryota , Yoshida Kaoru , Osumi Tomoo , Deguchi Takao , Mori Makiko , Arakawa Yuki , Takagi Masatoshi , Miyamura Takako , Sakaguchi Kimiyoshi , Toyoda Hidemi , Ishida Hisashi , Sakata Naoki , Imamura Toshihiko , Kawahara Yuta , Morimoto Akira , Koike Takashi , Yagasaki Hiroshi , Ito Shuichi , Tomizawa Daisuke , Kiyokawa Nobutaka , Narumi Satoshi , Kato Motohiro 
Published: August 2020

SummaryMonosomy 7 (−7) occurs in various types of paediatric myeloid disorders and has a poor prognosis. Recent studies have demonstrated that patients with germline gain‐of‐function SAMD9/9L variants and loss‐of‐function GATA2 variants are prone to developing myelodysplastic syndrome (MDS) associated with −7. However, the prevalence of the genetic variants among paediatric haematologic disorders with −7 is unknown. The present study screened germline variants of GATA2 and SAMD9/9L in 25 patients with various types of paediatric haematological disorders associated with −7. The diagnoses of the 25 patients included MDS (n = 10), acute myeloid leukaemia (AML) and myeloid sarcomas (n = 9), juvenile myelomonocytic leukaemia (n = 3) and other disorders (n = 3). Seven patients with a germline pathogenic GATA2 variant were found. For SAMD9/9L screening, next‐generation sequencing was used to detect low‐abundance variants and found four novel germline variants. Functional analysis revealed that three out of the four variants showed growth‐restricting capacity in vitro and thus, were judged to be pathogenic. Cases with GATA2 mutation tended to be older, compared to those with SAMD9/9L mutations. In conclusion, GATA2 and SAMD9/9L were sequenced in 25 patients with paediatric haematologic disorders associated with −7, and 40% of them were found to have some pathogenic germline variants in the three genes.
Targeting RNA helicase DHX33 blocks Ras‐driven lung tumorigenesis in vivo
Authors: Wang Xingshun , Feng Weimin , Peng Cheng , Chen Shiyun , Ji Hongbin , Zhong Hanbing , Ge Wei , Zhang Yandong 
Published: August 2020

AbstractRas has been found to be mutated in 30% of non‐small cell lung cancers, and its mutation has been regarded as a causal factor underlying tumorigenesis. However, no successful medicine has been developed so far to inhibit Ras for lung cancer treatment. We have previously identified DHX33 as a Ras downstream effector, promoting cell cycle progression and cell growth. In this study, with the K‐Ras (G12D);DHX33 (lox/lox) mouse model, we discovered that genetic ablation of DHX33 inhibited tumor development. We further found that ablation of DHX33 altered the expression of nearly 2000 genes which are critical in cancer development such as cell cycle, apoptosis, glycolysis, Wnt signaling, and cell migration. Our study for the first time demonstrates the pivotal role of the DHX33 in Ras‐driven lung cancer development in vivo and highlights that pharmacological targeting DHX33 can be a feasible option in treating Ras‐mutant lung cancers.
Caprylic acid (C8:0) promotes bone metastasis of prostate cancer by dysregulated adipo‐osteogenic balance in bone marrow
Authors: Wang Cuizhe , Wang Jingzhou , Chen Keru , Pang Huai , Li Xue , Zhu Jiaojiao , Ma Yinghua , Qiu Tongtong , Li Wei , Xie Jianxin , Zhang Jun 
Published: August 2020

AbstractProstate cancer (PCa) continues to be the most common, noncutaneous cancer in men. Bone is the most frequent site of PCa metastases, and up to 90% of patients with advanced PCa develop bone metastases. An altered bone marrow microenvironment, induced by obesity, is a significant mediator for the bone tropism of PCa. However, the specific molecular mechanisms by which obesity causes changes in the bone marrow microenvironment, leading to PCa bone metastasis, are not fully understood. Our results demonstrate that a high‐fat diet (HFD) leads to dyslipidemia and changes in bone marrow of nude mice: an increase in the area and number of adipocytes and a reduction in the area and number of osteoblasts. Moreover, a HFD promoted cyclooxygenase 2 (COX2) expression and inhibited osteoprotegerin (OPG) expression in the bone microenvironment. Additionally, the total level of free fatty acids (FFAs) and caprylic acid (C8:0) was significantly higher in PCa patients with bone metastases. In vitro, caprylic acid (C8:0) promoted bone mesenchymal stem cell (MSC)‐derived adipocytic differentiation, COX2 expression, and prostaglandin E2 (PGE2) secretion, whereas osteoblastic differentiation and OPG expression were reduced. Furthermore, caprylic acid (C8:0)‐treated adipocytes promoted the invasion and migration of PCa cells. Taken together, our findings suggest caprylic acid (C8:0) promotes bone metastasis of PCa by dysregulated adipo‐osteogenic balance of bone marrow.
Iron chelation cancer therapy using hydrophilic block copolymers conjugated with deferoxamine
Authors: Komoto Kana , Nomoto Takahiro , El Muttaqien Sjaikhurrizal , Takemoto Hiroyasu , Matsui Makoto , Miura Yutaka , Nishiyama Nobuhiro 
Published: August 2020

AbstractCancer cells have high iron requirements due to their rapid growth and proliferation. Iron depletion using iron chelators has a potential in cancer treatment. Previous studies have demonstrated that deferoxamine (DFO) specifically chelates Fe(III) and exhibited antitumor activity in clinical studies. However, its poor pharmacokinetics has limited the therapeutic potential and practical application. Although polymeric iron chelators have been developed to increase the blood retention, none of previous studies has demonstrated their potential in iron chelation cancer therapy. Here, we developed polymeric DFO by the covalent conjugation of DFO to poly(ethylene glycol)‐poly(aspartic acid) (PEG‐PAsp) block copolymers. The polymeric DFO exhibited iron‐chelating ability comparable with free DFO, thereby arresting cell cycle and inducing apoptosis and antiproliferative activity. After intravenous administration, the polymeric DFO showed marked increase in blood retention and tumor accumulation in subcutaneous tumor models. Consequently, polymeric DFO showed significant suppression of the tumor growth compared with free DFO. This study reveals the first success of the design of polymeric DFO for enhancing iron chelation cancer therapy.
How Does Children’s Theory of Mind Become Explicit? A Review of Longitudinal Findings
Authors: Sodian Beate , Kristen‐Antonow Susanne , Kloo Daniela 
Published: August 2020

AbstractHow does theory of mind become explicit? In this article, we provide a brief overview of theoretical accounts and then review longitudinal findings on the development of theory of mind from infancy to the preschool years. Long‐term predictive relations among conceptually related measures of implicit and explicit theory‐of‐mind reasoning support a conceptual continuity view of the transition from an implicit to an explicit understanding of the mind. We discuss alternative, minimalist accounts of infant psychological reasoning (e.g., two‐systems models, submentalizing theory) and their implications for the development of theory of mind in light of the evidence. Longitudinal findings further support a developmental enrichment view of joint attention as a foundation of theory of mind and early social interaction as a powerful mechanism in the development of this ability. Finally, we highlight the importance of longitudinal data for our understanding of conceptual development from infancy to the preschool years.
A Daily Examination of African American Adolescents’ Racial Discrimination, Parental Racial Socialization, and Psychological Affect
Authors: Cheeks Bridget L. , Chavous Tabbye M. , Sellers Robert M. 
Published: August 2020

This study examined 164 African American adolescents’ (Mage = 15) daily reports of racial discrimination and parental racial socialization over 21 days. The study examined same‐day and previous‐day associations of adolescents’ discrimination and socialization experiences with their positive and negative psychological affect. It further explored whether racial socialization messages buffered discrimination’s effects on affect when messages were received during the same day and on the day prior to discrimination. Findings indicated the deleterious effect of racial discrimination (associated with more negative affect) and highlighted the importance of examining youth’s short‐term coping in critical developmental years. Findings also showed how messages promote positive youth emotions. However, daily moderating associations differed from prior survey studies, suggesting the importance of examining short‐term processes.
Progressive Acquisition of SVBRDF and Shape in Motion
Authors: Ha Hyunho , Baek Seung‐Hwan , Nam Giljoo , Kim Min H. 
Published: August 2020

AbstractTo estimate appearance parameters, traditional SVBRDF acquisition methods require multiple input images to be captured with various angles of light and camera, followed by a post‐processing step. For this reason, subjects have been limited to static scenes, or a multiview system is required to capture dynamic objects. In this paper, we propose a simultaneous acquisition method of SVBRDF and shape allowing us to capture the material appearance of deformable objects in motion using a single RGBD camera. To do so, we progressively integrate photometric samples of surfaces in motion in a volumetric data structure with a deformation graph. Then, building upon recent advances of fusion‐based methods, we estimate SVBRDF parameters in motion. We make use of a conventional RGBD camera that consists of the colour and infrared cameras with active infrared illumination. The colour camera is used for capturing diffuse properties, and the infrared camera‐illumination module is employed for estimating specular properties by means of active illumination. Our joint optimization yields complete material appearance parameters. We demonstrate the effectiveness of our method with extensive evaluation on both synthetic and real data that include various deformable objects of specular and diffuse appearance.
Magnetic resonance imaging after ligation of the intersphincteric fistula tract for high perianal fistulas in Crohn's disease: a retrospective cohort study
Authors: Meima ‐ van Praag E. M. , van Rijn K. L. , Monraats M. A. , Buskens C. J. , Stoker J. 
Published: August 2020

AbstractAimLigation of the intersphincteric fistula tract (LIFT) is increasingly being used for surgical closure of high perianal fistulas in Crohn’s disease. Currently, data on postoperative MRI findings are scarce, although they are considered important for assessing healing and recurrence. Our aim, therefore, was to evaluate fistula characteristics on MRI and their relationship with clinical outcomes after LIFT.MethodConsecutive Crohn's patients treated with LIFT between 2007 and 2018 who underwent baseline and follow‐up MRI were retrospectively included. MRIs were scored by two radiologists according to characteristics based on the original and modified Van Assche indices. MRI findings, with emphasis on fibrosis, and the relationship with clinical healing, re‐interventions and recurrences are described.ResultsTwelve patients were included [four men, median age 34 (interquartile range 28–39) years]. Follow‐up MRI was performed at a median of 5.5 months (interquartile range 2.5–6.0) after LIFT. At baseline, all patients showed a tract with predominantly granulation tissue, which changed to predominantly fibrotic in seven (in three of whom it was completely fibrotic). All patients with a (predominantly) fibrotic tract had clinical closure and no re‐interventions or recurrences during long‐term follow‐up. In contrast, of the five patients with persisting granulation tissue, two reached clinical healing, two needed re‐intervention and one had a recurrence.ConclusionMarkedly decreased fistula activity can be observed on MRI after LIFT. The majority of patients develop a predominantly fibrotic tract relatively soon after LIFT without clinical recurrence, suggesting a highly effective therapy. Unfavourable clinical outcomes were only present in patients with persisting granulation tissue, indicating the potential prognostic value of MRI.
LncRNAs are regulated by chromatin states and affect the skeletal muscle cell differentiation
Authors: Qi Xiaolong , Hu Mingyang , Xiang Yue , Wang Daoyuan , Xu Yueyuan , Hou Ye , Zhou Huanhuan , Luan Yu , Wang Zhangxu , Zhang Weiya , Li Xinyun , Zhao Shuhong , Zhao Yunxia 
Published: August 2020

AbstractObjectiveThis study aims to clarify the mechanisms underlying transcriptional regulation and regulatory roles of lncRNAs in skeletal muscle cell differentiation.MethodsWe analysed the expression patterns of lncRNAs via time‐course RNA‐seq. Then, we further combined the ATAC‐seq and ChIP‐seq to investigate the governing mechanisms of transcriptional regulation of differentially expressed (DE) lncRNAs. Weighted correlation network analysis and GO analysis were conducted to identify the transcription factor (TF)‐lncRNA pairs related to skeletal muscle cell differentiation.ResultsWe identified 385 DE lncRNAs during C2C12 differentiation, the transcription of which is determined by chromatin states around their transcriptional start sites. The TF‐lncRNA correlation network showed substantially concordant changes in DE lncRNAs between C2C12 differentiation and satellite cell rapid growth stages. Moreover, the up‐regulated lncRNAs showed a significant decrease following the differentiation capacity of satellite cells, which gradually declines during skeletal muscle development. Notably, inhibition of the lncRNA Atcayos and Trp53cor1 led to the delayed differentiation of satellite cells. Those lncRNAs were significantly up‐regulated during the rapid growth stage of satellite cells (4‐6 weeks) and down‐regulated with reduced differentiation capacity (8‐12 weeks). It confirms that these lncRNAs are positively associated with myogenic differentiation of satellite cells during skeletal muscle development.ConclusionsThis study extends the understanding of mechanisms governing transcriptional regulation of lncRNAs and provides a foundation for exploring their functions in skeletal muscle cell differentiation.
Model Informed Dosing Regimen and Phase I Results of the Anti‐PD‐1 Antibody Budigalimab (ABBV‐181)
Authors: Powderly John , Spira Alexander , Kondo Shunsuke , Doi Toshihiko , Luke Jason J. , Rasco Drew , Gao Bo , Tanner Minna , Cassier Philippe A. , Gazzah Anas , Italiano Antoine , Tosi Diego , Afar Daniel E. , Parikh Apurvasena , Engelhardt Benjamin , Englert Stefan , Lambert Stacie L. , Kasichayanula Sreeneeranj , Mensing Sven , Menon Rajeev , Vosganian Gregory , Tolcher Anthony 
Published: August 2020

Budigalimab is a humanized, recombinant, Fc mutated IgG1 monoclonal antibody targeting programmed cell death 1 (PD‐1) receptor, currently in phase I clinical trials. The safety, efficacy, pharmacokinetics (PKs), pharmacodynamics (PDs), and budigalimab dose selection from monotherapy dose escalation and multihistology expansion cohorts were evaluated in patients with previously treated advanced solid tumors who received budigalimab at 1, 3, or 10 mg/kg intravenously every 2 weeks (Q2W) in dose escalation, including Japanese patients that received 3 and 10 mg/kg Q2W. PK modeling and PK/PD assessments informed the dosing regimen in expansion phase using data from body‐weight‐based dosing in the escalation phase, based on which patients in the multihistology expansion cohort received flat doses of 250 mg Q2W or 500 mg every four weeks (Q4W). Immune‐related adverse events (AEs) were reported in 11 of 59 patients (18.6%), of which 1 of 59 (1.7%) was considered grade ≥ 3 and the safety profile of budigalimab was consistent with other PD‐1 targeting agents. No treatment‐related grade 5 AEs were reported. Four responses per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 were reported in the dose escalation cohort and none in the multihistology expansion cohort. PK of budigalimab was approximately dose proportional and sustained > 99% peripheral PD‐1 receptor saturation was observed by 2 hours postdosing, across doses. PK/PD and safety profiles were comparable between Japanese and Western patients, and exposure‐safety analyses did not indicate any trends. Observed PK and PD‐1 receptor saturation were consistent with model predictions for flat doses and less frequent regimens, validating the early application of PK modeling and PK/PD assessments to inform the recommended dose and regimen, following dose escalation.
Epigenetic Changes Associated With Anthracycline‐Induced Cardiotoxicity
Authors: Tantawy Marwa , Pamittan Frances G. , Singh Sonal , Gong Yan 
Published: August 2020

Advances in cancer treatment have significantly improved the survival of patients with cancer, but, unfortunately, many of these treatments also have long‐term complications. Cancer treatment‐related cardiotoxicities are becoming a significant clinical problem that a new discipline, Cardio‐Oncology, was established to advance the cardiovascular care of patients with growing cancer populations. Anthracyclines are a class of chemotherapeutic agents used to treat many cancers in adults and children. Their clinical use is limited by anthracycline‐induced cardiotoxicity (AIC), which can lead to heart failure. Early‐onset cardiotoxicity appears within a year of treatment, whereas late‐onset cardiotoxicity occurs > 1 year and even up to decades after treatment completion. The pathophysiology of AIC was hypothesized to be caused by generation of reactive oxygen species that lead to lipid peroxidation, defective mitochondrial biogenesis, and DNA damage of the cardiomyocytes. The accumulation of anthracycline metabolites was also proposed to cause mitochondrial damage and the induction of cardiac cell apoptosis, which induces arrhythmias, contractile dysfunction, and cardiomyocyte death. This paper will provide a general overview of cardiotoxicity focusing on the effect of anthracyclines and their epigenetic molecular mechanisms on cardiotoxicity.
Fit‐for‐Purpose Biometric Monitoring Technologies: Leveraging the Laboratory Biomarker Experience
Authors: Godfrey Alan , Vandendriessche Benjamin , Bakker Jessie P. , Fitzer‐Attas Cheryl , Gujar Ninad , Hobbs Matthew , Liu Qi , Northcott Carrie A. , Parks Virginia , Wood William A. , Zipunnikov Vadim , Wagner John A. , Izmailova Elena S. 
Published: August 2020

Biometric monitoring technologies (BioMeTs) are becoming increasingly common to aid data collection in clinical trials and practice. The state of BioMeTs, and associated digitally measured biomarkers, is highly reminiscent of the field of laboratory biomarkers 2 decades ago. In this review, we have summarized and leveraged historical perspectives, and lessons learned from laboratory biomarkers as they apply to BioMeTs. Both categories share common features, including goals and roles in biomedical research, definitions, and many elements of the biomarker qualification framework. They can also be classified based on the underlying technology, each with distinct features and performance characteristics, which require bench and human experimentation testing phases. In contrast to laboratory biomarkers, digitally measured biomarkers require prospective data collection for purposes of analytical validation in human subjects, lack well‐established and widely accepted performance characteristics, require human factor testing, and, for many applications, access to raw (sample‐level) data. Novel methods to handle large volumes of data, as well as security and data rights requirements add to the complexity of this emerging field. Our review highlights the need for a common framework with appropriate vocabulary and standardized approaches to evaluate digitally measured biomarkers, including defining performance characteristics and acceptance criteria. Additionally, the need for human factor testing drives early patient engagement during technology development. Finally, use of BioMeTs requires a relatively high degree of technology literacy among both study participants and healthcare professionals. Transparency of data generation and the need for novel analytical and statistical tools creates opportunities for precompetitive collaborations.
Regular arrangement of collecting venules and the Kimura‐Takemoto classification for the endoscopic diagnosis of Helicobacter pylori infection: Evaluation in a Western setting
Authors: Ebigbo Alanna , Marienhagen Jörg , Messmann Helmut 
Published: August 2020

BackgroundThe regular arrangement of collecting venules (RAC) and the Kimura‐Takemoto classification of atrophic change (KTC) are simple and easy‐to‐use criteria which have been shown to reliably predict or rule out a Helicobacter pylori infection of the stomach. Although these features have been investigated extensively in Asia, their significance in the West has not been evaluated.MethodsIn a series of 200 consecutive gastroscopic examinations (single examiner, single center), the presence or absence of RAC and the KTC grade (open type vs closed type) were recorded prospectively. Helicobacter pylori infection was defined as a positive histology or a positive rapid urease test. Furthermore, multivariate analysis of endoscopic predictors of H. pylori infection based on the Kyoto classification of gastritis was performed.ResultsTwo hundred patients were examined of which 57 had a H. pylori infection (28%). Both RAC and KTC had excellent negative predictive values of about 90% and sensitivity values of up to 85%. In multivariate analysis, atrophic change and diffuse redness without RAC were significantly associated with H. pylori infection.ConclusionRegular arrangement of collecting venules and KTC are simple endoscopic features which should be given attention by Western endoscopists and can be easily used to rule out a H. pylori infection of the stomach.