bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lifestyles, genetics, and future perspectives on gastric cancer in east Asian populations
Authors: Katoh Hiroto , Ishikawa Shumpei 
Published: July 2021

AbstractThe prevalence of gastric cancer (GC) differs among regions worldwide, with the highest occurrence in east Asia. Thus, its etiology, with respect to ethnic background, environmental factors, and lifestyles, is also thought to differ essentially. In addition, etiology of GC is speculated to be changing due to the recent decrease in the Helicobacter pylori (H. pylori) infection in Japan. State-of-the-art somatic/germline cancer genomics has clarified the etiologies of gastric carcinogenesis. In this review article, we summarize past and present milestones in our understanding of GC achieved through genomic approaches, including a recent report that revealed higher-than-expected frequencies of GCs attributed to east Asian-specific germline variants in ALDH2 or CDH1 in combination with lifestyles. Based on this updated knowledge, we also discuss the possible impact of and high-risk approaches for GCs in the upcoming “H. pylori-negative era.”
Pharmacological inhibitors of anaplastic lymphoma kinase (ALK) induce immunogenic cell death through on-target effects
Authors: Petrazzuolo Adriana , Perez-Lanzon Maria , Martins Isabelle , Liu Peng , Kepp Oliver , Minard-Colin Véronique , Maiuri Maria Chiara , Kroemer Guido 
Published: July 2021

AbstractImmunogenic cell death (ICD) is clinically relevant because cytotoxicants that kill malignant cells via ICD elicit anticancer immune responses that prolong the effects of chemotherapies beyond treatment discontinuation. ICD is characterized by a series of stereotyped changes that increase the immunogenicity of dying cells: exposure of calreticulin on the cell surface, release of ATP and high mobility group box 1 protein, as well as a type I interferon response. Here, we examined the possibility that inhibition of an oncogenic kinase, anaplastic lymphoma kinase (ALK), might trigger ICD in anaplastic large cell lymphoma (ALCL) in which ALK is activated due to a chromosomal translocation. Multiple lines of evidence plead in favor of specific ICD-inducing effects of crizotinib and ceritinib in ALK-dependent ALCL: (i) they induce ICD stigmata at pharmacologically relevant, low concentrations; (ii) can be mimicked in their ICD-inducing effects by ALK knockdown; (iii) lose their effects in the context of resistance-conferring ALK mutants; (iv) ICD-inducing effects are mimicked by inhibition of the signal transduction pathways operating downstream of ALK. When ceritinib-treated murine ALK-expressing ALCL cells were inoculated into the left flank of immunocompetent syngeneic mice, they induced an immune response that slowed down the growth of live ALCL cells implanted in the right flank. Although ceritinib induced a transient shrinkage of tumors in lymphoma-bearing mice, irrespective of their immunocompetence, relapses occurred more frequently in the context of immunodeficiency, reducing the effects of ceritinib on survival by approximately 50%. Complete cure only occurred in immunocompetent mice and conferred protection to rechallenge with the same ALK-expressing lymphoma but not with another unrelated lymphoma. Moreover, immunotherapy with PD-1 blockade tended to increase cure rates. Altogether, these results support the contention that specific ALK inhibition stimulates the immune system by inducing ICD in ALK-positive ALCL.
Renewable fatty acid ester production in Clostridium
Authors: Feng Jun , Zhang Jie , Ma Yuechao , Feng Yiming , Wang Shangjun , Guo Na , Wang Haijiao , Wang Pixiang , Jiménez-Bonilla Pablo , Gu Yanyan , Zhou Junping , Zhang Zhong-Tian , Cao Mingfeng , Jiang Di , Wang Shuning , Liu Xian-Wei , Shao Zengyi , Borovok Ilya , Huang Haibo , Wang Yi 
Published: July 2021

AbstractBioproduction of renewable chemicals is considered as an urgent solution for fossil energy crisis. However, despite tremendous efforts, it is still challenging to generate microbial strains that can produce target biochemical to high levels. Here, we report an example of biosynthesis of high-value and easy-recoverable derivatives built upon natural microbial pathways, leading to improvement in bioproduction efficiency. By leveraging pathways in solventogenic clostridia for co-producing acyl-CoAs, acids and alcohols as precursors, through rational screening for host strains and enzymes, systematic metabolic engineering-including elimination of putative prophages, we develop strains that can produce 20.3 g/L butyl acetate and 1.6 g/L butyl butyrate. Techno-economic analysis results suggest the economic competitiveness of our developed bioprocess. Our principles of selecting the most appropriate host for specific bioproduction and engineering microbial chassis to produce high-value and easy-separable end products may be applicable to other bioprocesses.
Associations between dimensions of behaviour, personality traits, and mental-health during the COVID-19 pandemic in the United Kingdom
Authors: Hampshire Adam , Hellyer Peter J. , Soreq Eyal , Mehta Mitul A. , Ioannidis Konstantinos , Trender William , Grant Jon E. , Chamberlain Samuel R. 
Published: July 2021

AbstractThe COVID-19 pandemic (including lockdown) is likely to have had profound but diverse implications for mental health and well-being, yet little is known about individual experiences of the pandemic (positive and negative) and how this relates to mental health and well-being, as well as other important contextual variables. Here, we analyse data sampled in a large-scale manner from 379,875 people in the United Kingdom (UK) during 2020 to identify population variables associated with mood and mental health during the COVID-19 pandemic, and to investigate self-perceived pandemic impact in relation to those variables. We report that while there are relatively small population-level differences in mood assessment scores pre- to peak-UK lockdown, the size of the differences is larger for people from specific groups, e.g. older adults and people with lower incomes. Multiple dimensions underlie peoples’ perceptions, both positive and negative, of the pandemic’s impact on daily life. These dimensions explain variance in mental health and can be statistically predicted from age, demographics, home and work circumstances, pre-existing conditions, maladaptive technology use and personality traits (e.g., compulsivity). We conclude that a holistic view, incorporating the broad range of relevant population factors, can better characterise people whose mental health is most at risk during the COVID-19 pandemic.
Discovery and prioritization of variants and genes for kidney function in >1.2 million individuals
Authors: Stanzick Kira J. , Li Yong , Schlosser Pascal , Gorski Mathias , Wuttke Matthias , Thomas Laurent F. , Rasheed Humaira , Rowan Bryce X. , Graham Sarah E. , Vanderweff Brett R. , Patil Snehal B. ,   VA Million Veteran Program, Robinson-Cohen Cassiane , Gaziano John M. , O’Donnell Christopher J. , Willer Cristen J. , Hallan Stein , Åsvold Bjørn Olav , Gessner Andre , Hung Adriana M. , Pattaro Cristian , Köttgen Anna , Stark Klaus J. , Heid Iris M. , Winkler Thomas W. 
Published: July 2021

AbstractGenes underneath signals from genome-wide association studies (GWAS) for kidney function are promising targets for functional studies, but prioritizing variants and genes is challenging. By GWAS meta-analysis for creatinine-based estimated glomerular filtration rate (eGFR) from the Chronic Kidney Disease Genetics Consortium and UK Biobank (n = 1,201,909), we expand the number of eGFRcrea loci (424 loci, 201 novel; 9.8% eGFRcrea variance explained by 634 independent signal variants). Our increased sample size in fine-mapping (n = 1,004,040, European) more than doubles the number of signals with resolved fine-mapping (99% credible sets down to 1 variant for 44 signals, ≤5 variants for 138 signals). Cystatin-based eGFR and/or blood urea nitrogen association support 348 loci (n = 460,826 and 852,678, respectively). Our customizable tool for Gene PrioritiSation reveals 23 compelling genes including mechanistic insights and enables navigation through genes and variants likely relevant for kidney function in human to help select targets for experimental follow-up.
Structure of PDE3A-SLFN12 complex reveals requirements for activation of SLFN12 RNase
Authors: Garvie Colin W. , Wu Xiaoyun , Papanastasiou Malvina , Lee Sooncheol , Fuller James , Schnitzler Gavin R. , Horner Steven W. , Baker Andrew , Zhang Terry , Mullahoo James P. , Westlake Lindsay , Hoyt Stephanie H. , Toetzl Marcus , Ranaghan Matthew J. , de Waal Luc , McGaunn Joseph , Kaplan Bethany , Piccioni Federica , Yang Xiaoping , Lange Martin , Tersteegen Adrian , Raymond Donald , Lewis Timothy A. , Carr Steven A. , Cherniack Andrew D. , Lemke Christopher T. , Meyerson Matthew , Greulich Heidi 
Published: July 2021

AbstractDNMDP and related compounds, or velcrins, induce complex formation between the phosphodiesterase PDE3A and the SLFN12 protein, leading to a cytotoxic response in cancer cells that express elevated levels of both proteins. The mechanisms by which velcrins induce complex formation, and how the PDE3A-SLFN12 complex causes cancer cell death, are not fully understood. Here, we show that PDE3A and SLFN12 form a heterotetramer stabilized by binding of DNMDP. Interactions between the C-terminal alpha helix of SLFN12 and residues near the active site of PDE3A are required for complex formation, and are further stabilized by interactions between SLFN12 and DNMDP. Moreover, we demonstrate that SLFN12 is an RNase, that PDE3A binding increases SLFN12 RNase activity, and that SLFN12 RNase activity is required for DNMDP response. This new mechanistic understanding will facilitate development of velcrin compounds into new cancer therapies.
Complete loss of H3K9 methylation dissolves mouse heterochromatin organization
Authors: Montavon Thomas , Shukeir Nicholas , Erikson Galina , Engist Bettina , Onishi-Seebacher Megumi , Ryan Devon , Musa Yaarub , Mittler Gerhard , Meyer Alexandra Graff , Genoud Christel , Jenuwein Thomas 
Published: July 2021

AbstractHistone H3 lysine 9 (H3K9) methylation is a central epigenetic modification that defines heterochromatin from unicellular to multicellular organisms. In mammalian cells, H3K9 methylation can be catalyzed by at least six distinct SET domain enzymes: Suv39h1/Suv39h2, Eset1/Eset2 and G9a/Glp. We used mouse embryonic fibroblasts (MEFs) with a conditional mutation for Eset1 and introduced progressive deletions for the other SET domain genes by CRISPR/Cas9 technology. Compound mutant MEFs for all six SET domain lysine methyltransferase (KMT) genes lack all H3K9 methylation states, derepress nearly all families of repeat elements and display genomic instabilities. Strikingly, the 6KO H3K9 KMT MEF cells no longer maintain heterochromatin organization and have lost electron-dense heterochromatin. This is a compelling analysis of H3K9 methylation-deficient mammalian chromatin and reveals a definitive function for H3K9 methylation in protecting heterochromatin organization and genome integrity.
Parallel processing of working memory and temporal information by distinct types of cortical projection neurons
Authors: Bae Jung Won , Jeong Huijeong , Yoon Young Ju , Bae Chan Mee , Lee Hyeonsu , Paik Se-Bum , Jung Min Whan 
Published: July 2021

AbstractIt is unclear how different types of cortical projection neurons work together to support diverse cortical functions. We examined the discharge characteristics and inactivation effects of intratelencephalic (IT) and pyramidal tract (PT) neurons—two major types of cortical excitatory neurons that project to cortical and subcortical structures, respectively—in the deep layer of the medial prefrontal cortex in mice performing a delayed response task. We found stronger target-dependent firing of IT than PT neurons during the delay period. We also found the inactivation of IT neurons, but not PT neurons, impairs behavioral performance. In contrast, PT neurons carry more temporal information than IT neurons during the delay period. Our results indicate a division of labor between IT and PT projection neurons in the prefrontal cortex for the maintenance of working memory and for tracking the passage of time, respectively.
Innate-like self-reactive B cells infiltrate human renal allografts during transplant rejection
Authors: Asano Yuta , Daccache Joe , Jain Dharmendra , Ko Kichul , Kinloch Andrew , Veselits Margaret , Wolfgeher Donald , Chang Anthony , Josephson Michelle , Cunningham Patrick , Tambur Anat , Khan Aly A. , Pillai Shiv , Chong Anita S. , Clark Marcus R. 
Published: July 2021

AbstractIntrarenal B cells in human renal allografts indicate transplant recipients with a poor prognosis, but how these cells contribute to rejection is unclear. Here we show using single-cell RNA sequencing that intrarenal class-switched B cells have an innate cell transcriptional state resembling mouse peritoneal B1 or B-innate (Bin) cells. Antibodies generated by Bin cells do not bind donor-specific antigens nor are they enriched for reactivity to ubiquitously expressed self-antigens. Rather, Bin cells frequently express antibodies reactive with either renal-specific or inflammation-associated antigens. Furthermore, local antigens can drive Bin cell proliferation and differentiation into plasma cells expressing self-reactive antibodies. These data show a mechanism of human inflammation in which a breach in organ-restricted tolerance by infiltrating innate-like B cells drives local tissue destruction.
The molecular basis of regulation of bacterial capsule assembly by Wzc
Authors: Yang Yun , Liu Jiwei , Clarke Bradley R. , Seidel Laura , Bolla Jani R. , Ward Philip N. , Zhang Peijun , Robinson Carol V. , Whitfield Chris , Naismith James H. 
Published: July 2021

AbstractBacterial extracellular polysaccharides (EPSs) play critical roles in virulence. Many bacteria assemble EPSs via a multi-protein “Wzx-Wzy” system, involving glycan polymerization at the outer face of the cytoplasmic/inner membrane. Gram-negative species couple polymerization with translocation across the periplasm and outer membrane and the master regulator of the system is the tyrosine autokinase, Wzc. This near atomic cryo-EM structure of dephosphorylated Wzc from E. coli shows an octameric assembly with a large central cavity formed by transmembrane helices. The tyrosine autokinase domain forms the cytoplasm region, while the periplasmic region contains small folded motifs and helical bundles. The helical bundles are essential for function, most likely through interaction with the outer membrane translocon, Wza. Autophosphorylation of the tyrosine-rich C-terminus of Wzc results in disassembly of the octamer into multiply phosphorylated monomers. We propose that the cycling between phosphorylated monomer and dephosphorylated octamer regulates glycan polymerization and translocation.
Designing polymer nanocomposites with high energy density using machine learning
Authors: Shen Zhong-Hui , Bao Zhi-Wei , Cheng Xiao-Xing , Li Bao-Wen , Liu Han-Xing , Shen Yang , Chen Long-Qing , Li Xiao-Guang , Nan Ce-Wen 
Published: July 2021

AbstractAddressing microstructure-property relations of polymer nanocomposites is vital for designing advanced dielectrics for electrostatic energy storage. Here, we develop an integrated phase-field model to simulate the dielectric response, charge transport, and breakdown process of polymer nanocomposites. Subsequently, based on 6615 high-throughput calculation results, a machine learning strategy is schemed to evaluate the capability of energy storage. We find that parallel perovskite nanosheets prefer to block and then drive charges to migrate along with the interfaces in x-y plane, which could significantly improve the breakdown strength of polymer nanocomposites. To verify our predictions, we fabricate a polymer nanocomposite P(VDF-HFP)/Ca2Nb3O10, whose highest discharged energy density almost doubles to 35.9 J cm−3 compared with the pristine polymer, mainly benefit from the improved breakdown strength of 853 MV m−1. This work opens a horizon to exploit the great potential of 2D perovskite nanosheets for a wide range of applications of flexible dielectrics with the requirement of high voltage endurance.
A Bayesian analysis of classical shadows
Authors: Lukens Joseph M. , Law Kody J. H. , Bennink Ryan S. 
Published: July 2021

AbstractThe method of classical shadows proposed by Huang, Kueng, and Preskill heralds remarkable opportunities for quantum estimation with limited measurements. Yet its relationship to established quantum tomographic approaches, particularly those based on likelihood models, remains unclear. In this article, we investigate classical shadows through the lens of Bayesian mean estimation (BME). In direct tests on numerical data, BME is found to attain significantly lower error on average, but classical shadows prove remarkably more accurate in specific situations—such as high-fidelity ground truth states—which are improbable in a fully uniform Hilbert space. We then introduce an observable-oriented pseudo-likelihood that successfully emulates the dimension-independence and state-specific optimality of classical shadows, but within a Bayesian framework that ensures only physical states. Our research reveals how classical shadows effect important departures from conventional thinking in quantum state estimation, as well as the utility of Bayesian methods for uncovering and formalizing statistical assumptions.
A DICOM dataset for evaluation of medical image de-identification
Authors: Rutherford Michael , Mun Seong K. , Levine Betty , Bennett William , Smith Kirk , Farmer Phil , Jarosz Quasar , Wagner Ulrike , Freyman John , Blake Geri , Tarbox Lawrence , Farahani Keyvan , Prior Fred 
Published: July 2021

AbstractWe developed a DICOM dataset that can be used to evaluate the performance of de-identification algorithms. DICOM objects (a total of 1,693 CT, MRI, PET, and digital X-ray images) were selected from datasets published in the Cancer Imaging Archive (TCIA). Synthetic Protected Health Information (PHI) was generated and inserted into selected DICOM Attributes to mimic typical clinical imaging exams. The DICOM Standard and TCIA curation audit logs guided the insertion of synthetic PHI into standard and non-standard DICOM data elements. A TCIA curation team tested the utility of the evaluation dataset. With this publication, the evaluation dataset (containing synthetic PHI) and de-identified evaluation dataset (the result of TCIA curation) are released on TCIA in advance of a competition, sponsored by the National Cancer Institute (NCI), for algorithmic de-identification of medical image datasets. The competition will use a much larger evaluation dataset constructed in the same manner. This paper describes the creation of the evaluation datasets and guidelines for their use.
3D printed microfluidic lab-on-a-chip device for fiber-based dual beam optical manipulation
Authors: Wang Haoran , Enders Anton , Preuss John-Alexander , Bahnemann Janina , Heisterkamp Alexander , Torres-Mapa Maria Leilani 
Published: July 2021

Abstract3D printing of microfluidic lab-on-a-chip devices enables rapid prototyping of robust and complex structures. In this work, we designed and fabricated a 3D printed lab-on-a-chip device for fiber-based dual beam optical manipulation. The final 3D printed chip offers three key features, such as (1) an optimized fiber channel design for precise alignment of optical fibers, (2) an optically clear window to visualize the trapping region, and (3) a sample channel which facilitates hydrodynamic focusing of samples. A square zig–zag structure incorporated in the sample channel increases the number of particles at the trapping site and focuses the cells and particles during experiments when operating the chip at low Reynolds number. To evaluate the performance of the device for optical manipulation, we implemented on-chip, fiber-based optical trapping of different-sized microscopic particles and performed trap stiffness measurements. In addition, optical stretching of MCF-7 cells was successfully accomplished for the purpose of studying the effects of a cytochalasin metabolite, pyrichalasin H, on cell elasticity. We observed distinct changes in the deformability of single cells treated with pyrichalasin H compared to untreated cells. These results demonstrate that 3D printed microfluidic lab-on-a-chip devices offer a cost-effective and customizable platform for applications in optical manipulation.
Pattern interaction effect
Authors: Floryan J. M. , Inasawa A. 
Published: July 2021

AbstractUnexpected responses of physical systems to external stimuli can be observed when the stimuli are organized into spatial patterns and, especially, when stimuli of different physical origins are involved, leading to the pattern interaction problem. Combinations of weak stimuli—individually only capable of producing marginal local responses—can produce a global response without involving any bifurcations. Its existence is demonstrated by the interaction of properly tuned topography and temperature patterns. When these patterns overlap in a symmetry preserving manner, the resulting convection has the form of local rolls. When these patterns are misaligned, the resulting convection involves global horizontal particle movement with direction depending on the type of misalignment.
Physical collection and viability of airborne bacteria collected under electrostatic field with different sampling media and protocols towards rapid detection
Authors: Hong Seongkyeol , Kim Myeong-Woo , Jang Jaesung 
Published: July 2021

AbstractElectrostatic samplers have been increasingly studied for sampling of viral and bacterial aerosols, and bioaerosol samplers are required to provide concentrated liquid samples with high physical collection and biological recovery, which would be critical for rapid detection. Here, the effects of sampling media and protocols on the physical collection and biological recovery of two airborne bacteria (Pseudomonas fluorescens and Micrococcus luteus) under electrostatic field were investigated using a personal electrostatic particle concentrator (EPC). Deionized (DI) water with/without sodium dodecyl sulfate (SDS) and phosphate buffered saline were tested as sampling media. A polystyrene container was mounted onto the collection electrode of the EPC for stable storage and vortexing after capture. Many bacterial cells were found to be deposited on the bottom surface of the container submerged in the media via electrophoresis, and among the tested sampling protocols, wet sampling with a container and subsequent vortexing offered the most bacteria in the collection suspension. Experiments with several sampling media showed that 0.001–0.01% SDS-DI water demonstrated the highest recovery rate in the EPC. These findings would be valuable in the field of sampling and subsequent rapid detection of bioaerosols.