bluuebunny/crossref_metadata_2025_split huggingface dataset:
The current treatment landscape in the UK for stage III NSCLC
Authors:   on behalf of AstraZeneca UK Limited, Evison Matthew 
Published: December 2020

AbstractFor stage III non-small cell lung cancer (NSCLC), approximately a third of patients survive up to 5 years, with decreasing 5-year survival rates for stage IIIB and stage IIIC disease. Although curable, stage III NSCLC encompasses a diverse range of disease presentation, with an equally complex range of multi-modal treatment options, including systemic and local therapies for distant and local disease control, respectively. This complexity results in a number of challenges for the multi-disciplinary team (MDT) in achieving optimal treatment outcomes for patients. As multi-modality treatment is the preferred treatment strategy for all stage III disease, the focus of this article is the key surgical, chemotherapy and radiotherapy clinical trials as well as guidelines that currently outline radical therapy options for patients with both potentially resectable and unresectable stage III NSCLC.
Global immune characterization of HBV/HCV-related hepatocellular carcinoma identifies macrophage and T-cell subsets associated with disease progression
Authors: Song Guohe , Shi Yang , Zhang Meiying , Goswami Shyamal , Afridi Saifullah , Meng Lu , Ma Jiaqiang , Chen Yi , Lin Youpei , Zhang Juan , Liu Yuming , Jin Zijie , Yang Shuaixi , Rao Dongning , Zhang Shu , Ke Aiwu , Wang Xiaoying , Cao Ya , Zhou Jian , Fan Jia , Zhang Xiaoming , Xi Ruibin , Gao Qiang 
Published: December 2020

AbstractDiverse immune cells in the tumor microenvironment form a complex ecosystem, but our knowledge of their heterogeneity and dynamics within hepatocellular carcinoma (HCC) still remains limited. To assess the plasticity and phenotypes of immune cells within HBV/HCV-related HCC microenvironment at single-cell level, we performed single-cell RNA sequencing on 41,698 immune cells from seven pairs of HBV/HCV-related HCC tumors and non-tumor liver tissues. We combined bio-informatic analyses, flow cytometry, and multiplex immunohistochemistry to assess the heterogeneity of different immune cell subsets in functional characteristics, transcriptional regulation, phenotypic switching, and interactions. We identified 29 immune cell subsets of myeloid cells, NK cells, and lymphocytes with unique transcriptomic profiles in HCC. A highly complex immunological network was shaped by diverse immune cell subsets that can transit among different states and mutually interact. Notably, we identified a subset of M2 macrophage with high expression of CCL18 and transcription factor CREM that was enriched in advanced HCC patients, and potentially participated in tumor progression. We also detected a new subset of activated CD8+ T cells highly expressing XCL1 that correlated with better patient survival rates. Meanwhile, distinct transcriptomic signatures, cytotoxic phenotypes, and evolution trajectory of effector CD8+ T cells from early-stage to advanced HCC were also identified. Our study provides insight into the immune microenvironment in HBV/HCV-related HCC and highlights novel macrophage and T-cell subsets that could be further exploited in future immunotherapy.
Faster chiral versus collinear magnetic order recovery after optical excitation revealed by femtosecond XUV scattering
Authors: Kerber Nico , Ksenzov Dmitriy , Freimuth Frank , Capotondi Flavio , Pedersoli Emanuele , Lopez-Quintas Ignacio , Seng Boris , Cramer Joel , Litzius Kai , Lacour Daniel , Zabel Hartmut , Mokrousov Yuriy , Kläui Mathias , Gutt Christian 
Published: December 2020

AbstractWhile chiral spin structures stabilized by Dzyaloshinskii-Moriya interaction (DMI) are candidates as novel information carriers, their dynamics on the fs-ps timescale is little known. Since with the bulk Heisenberg exchange and the interfacial DMI two distinct exchange mechanisms are at play, the ultrafast dynamics of the chiral order needs to be ascertained and compared to the dynamics of the conventional collinear order. Using an XUV free-electron laser we determine the fs-ps temporal evolution of the chiral order in domain walls in a magnetic thin film sample by an IR pump - X-ray magnetic scattering probe experiment. Upon demagnetization we observe that the dichroic (CL-CR) signal connected with the chiral order correlator mzmx in the domain walls recovers significantly faster than the (CL + CR) sum signal representing the average collinear domain magnetization mz2 + mx2. We explore possible explanations based on spin structure dynamics and reduced transversal magnetization fluctuations inside the domain walls and find that the latter can explain the experimental data leading to different dynamics for collinear magnetic order and chiral magnetic order.
RNA structure-wide discovery of functional interactions with multiplexed RNA motif library
Authors: Komatsu Kaoru R. , Taya Toshiki , Matsumoto Sora , Miyashita Emi , Kashida Shunnichi , Saito Hirohide 
Published: December 2020

AbstractBiochemical assays and computational analyses have discovered RNA structures throughout various transcripts. However, the roles of these structures are mostly unknown. Here we develop folded RNA element profiling with structure library (FOREST), a multiplexed affinity assay system to identify functional interactions from transcriptome-wide RNA structure datasets. We generate an RNA structure library by extracting validated or predicted RNA motifs from gene-annotated RNA regions. The RNA structure library with an affinity enrichment assay allows for the comprehensive identification of target-binding RNA sequences and structures in a high-throughput manner. As a proof-of-concept, FOREST discovers multiple RNA-protein interaction networks with quantitative scores, including translational regulatory elements that function in living cells. Moreover, FOREST reveals different binding landscapes of RNA G-quadruplex (rG4) structures-binding proteins and discovers rG4 structures in the terminal loops of precursor microRNAs. Overall, FOREST serves as a versatile platform to investigate RNA structure-function relationships on a large scale.
Engineering rules that minimize germline silencing of transgenes in simple extrachromosomal arrays in C. elegans
Authors: Aljohani Mohammed D. , El Mouridi Sonia , Priyadarshini Monika , Vargas-Velazquez Amhed M. , Frøkjær-Jensen Christian 
Published: December 2020

AbstractTransgenes are prone to progressive silencing due to their structure, copy number, and genomic location. In C. elegans, repressive mechanisms are particularly strong in the germline with almost fully penetrant transgene silencing in simple extrachromosomal arrays and frequent silencing of single-copy transgene insertions. A class of non-coding DNA, Periodic An/Tn Clusters (PATCs) can prevent transgene-silencing in repressive chromatin or from small interfering RNAs (piRNAs). Here, we describe design rules (codon-optimization, intron and PATC inclusion, elevated temperature (25 °C), and vector backbone removal) for efficient germline expression from arrays in wildtype animals. We generate web-based tools to analyze PATCs and reagents for the convenient assembly of PATC-rich transgenes. An extensive collection of silencing resistant fluorescent proteins (e.g., gfp, mCherry, and tagBFP) can be used for dissecting germline regulatory elements and a set of enhanced enzymes (Mos1 transposase, Cas9, Cre, and Flp recombinases) enable efficient genetic engineering in C. elegans.
Hybrid guided space-time optical modes in unpatterned films
Authors: Shiri Abbas , Yessenov Murat , Webster Scott , Schepler Kenneth L. , Abouraddy Ayman F. 
Published: December 2020

AbstractLight is confined transversely and delivered axially in a waveguide. However, waveguides are lossy static structures whose modal characteristics are fundamentally determined by their boundary conditions. Here we show that unpatterned planar waveguides can provide low-loss two-dimensional waveguiding by using space-time wave packets, which are unique one-dimensional propagation-invariant pulsed optical beams. We observe hybrid guided space-time modes that are index-guided in one transverse dimension and localized along the unbounded dimension. We confirm that these fields enable overriding the boundary conditions by varying post-fabrication the group index of the fundamental mode in a 2-μm-thick, 25-mm-long silica film, achieved by modifying the field’s spatio-temporal structure. Tunability of the group index over an unprecedented range from 1.26 to 1.77 is verified while maintaining a spectrally flat zero-dispersion profile. Our work paves the way to utilizing space-time wave packets in on-chip platforms, and enable phase-matching strategies that circumvent restrictions due to intrinsic material properties.
Plant-based and cell-based approaches to meat production
Authors: Rubio Natalie R. , Xiang Ning , Kaplan David L. 
Published: December 2020

AbstractAdvances in farming technology and intensification of animal agriculture increase the cost-efficiency and production volume of meat. Thus, in developed nations, meat is relatively inexpensive and accessible. While beneficial for consumer satisfaction, intensive meat production inflicts negative externalities on public health, the environment and animal welfare. In response, groups within academia and industry are working to improve the sensory characteristics of plant-based meat and pursuing nascent approaches through cellular agriculture methodology (i.e., cell-based meat). Here we detail the benefits and challenges of plant-based and cell-based meat alternatives with regard to production efficiency, product characteristics and impact categories.
Design of efficacious somatic cell genome editing strategies for recessive and polygenic diseases
Authors: Carlson-Stevermer Jared , Das Amritava , Abdeen Amr A. , Fiflis David , Grindel Benjamin I , Saxena Shivani , Akcan Tugce , Alam Tausif , Kletzien Heidi , Kohlenberg Lucille , Goedland Madelyn , Dombroe Micah J. , Saha Krishanu 
Published: December 2020

AbstractCompound heterozygous recessive or polygenic diseases could be addressed through gene correction of multiple alleles. However, targeting of multiple alleles using genome editors could lead to mixed genotypes and adverse events that amplify during tissue morphogenesis. Here we demonstrate that Cas9-ribonucleoprotein-based genome editors can correct two distinct mutant alleles within a single human cell precisely. Gene-corrected cells in an induced pluripotent stem cell model of Pompe disease expressed the corrected transcript from both corrected alleles, leading to enzymatic cross-correction of diseased cells. Using a quantitative in silico model for the in vivo delivery of genome editors into the developing human infant liver, we identify progenitor targeting, delivery efficiencies, and suppression of imprecise editing outcomes at the on-target site as key design parameters that control the efficacy of various therapeutic strategies. This work establishes that precise gene editing to correct multiple distinct gene variants could be highly efficacious if designed appropriately.
Macrophage ATP citrate lyase deficiency stabilizes atherosclerotic plaques
Authors: Baardman Jeroen , Verberk Sanne G. S. , van der Velden Saskia , Gijbels Marion J. J. , van Roomen Cindy P. P. A. , Sluimer Judith C. , Broos Jelle Y. , Griffith Guillermo R. , Prange Koen H. M. , van Weeghel Michel , Lakbir Soufyan , Molenaar Douwe , Meinster Elisa , Neele Annette E. , Kooij Gijs , de Vries Helga E. , Lutgens Esther , Wellen Kathryn E. , de Winther Menno P. J. , Van den Bossche Jan 
Published: December 2020

AbstractMacrophages represent a major immune cell population in atherosclerotic plaques and play central role in the progression of this lipid-driven chronic inflammatory disease. Targeting immunometabolism is proposed as a strategy to revert aberrant macrophage activation to improve disease outcome. Here, we show ATP citrate lyase (Acly) to be activated in inflammatory macrophages and human atherosclerotic plaques. We demonstrate that myeloid Acly deficiency induces a stable plaque phenotype characterized by increased collagen deposition and fibrous cap thickness, along with a smaller necrotic core. In-depth functional, lipidomic, and transcriptional characterization indicate deregulated fatty acid and cholesterol biosynthesis and reduced liver X receptor activation within the macrophages in vitro. This results in macrophages that are more prone to undergo apoptosis, whilst maintaining their capacity to phagocytose apoptotic cells. Together, our results indicate that targeting macrophage metabolism improves atherosclerosis outcome and we reveal Acly as a promising therapeutic target to stabilize atherosclerotic plaques.
HIF1A signaling selectively supports proliferation of breast cancer in the brain
Authors: Ebright Richard Y. , Zachariah Marcus A. , Micalizzi Douglas S. , Wittner Ben S. , Niederhoffer Kira L. , Nieman Linda T. , Chirn Brian , Wiley Devon F. , Wesley Benjamin , Shaw Brian , Nieblas-Bedolla Edwin , Atlas Lian , Szabolcs Annamaria , Iafrate Anthony J. , Toner Mehmet , Ting David T. , Brastianos Priscilla K. , Haber Daniel A. , Maheswaran Shyamala 
Published: December 2020

AbstractBlood-borne metastasis to the brain is a major complication of breast cancer, but cellular pathways that enable cancer cells to selectively grow in the brain microenvironment are poorly understood. We find that cultured circulating tumor cells (CTCs), derived from blood samples of women with advanced breast cancer and directly inoculated into the mouse frontal lobe, exhibit striking differences in proliferative potential in the brain. Derivative cell lines generated by serial intracranial injections acquire selectively increased proliferative competency in the brain, with reduced orthotopic tumor growth. Increased Hypoxia Inducible Factor 1A (HIF1A)-associated signaling correlates with enhanced proliferation in the brain, and shRNA-mediated suppression of HIF1A or drug inhibition of HIF-associated glycolytic pathways selectively impairs brain tumor growth while minimally impacting mammary tumor growth. In clinical specimens, brain metastases have elevated HIF1A protein expression, compared with matched primary breast tumors, and in patients with brain metastases, hypoxic signaling within CTCs predicts decreased overall survival. The selective activation of hypoxic signaling by metastatic breast cancer in the brain may have therapeutic implications.
Heme biosynthesis depends on previously unrecognized acquisition of iron-sulfur cofactors in human amino-levulinic acid dehydratase
Authors: Liu Gang , Sil Debangsu , Maio Nunziata , Tong Wing-Hang , Bollinger J. Martin , Krebs Carsten , Rouault Tracey Ann 
Published: December 2020

AbstractHeme biosynthesis and iron-sulfur cluster (ISC) biogenesis are two major mammalian metabolic pathways that require iron. It has long been known that these two pathways interconnect, but the previously described interactions do not fully explain why heme biosynthesis depends on intact ISC biogenesis. Herein we identify a previously unrecognized connection between these two pathways through our discovery that human aminolevulinic acid dehydratase (ALAD), which catalyzes the second step of heme biosynthesis, is an Fe-S protein. We find that several highly conserved cysteines and an Ala306-Phe307-Arg308 motif of human ALAD are important for [Fe4S4] cluster acquisition and coordination. The enzymatic activity of human ALAD is greatly reduced upon loss of its Fe-S cluster, which results in reduced heme biosynthesis in human cells. As ALAD provides an early Fe-S-dependent checkpoint in the heme biosynthetic pathway, our findings help explain why heme biosynthesis depends on intact ISC biogenesis.
The CloudUPDRS smartphone software in Parkinson’s study: cross-validation against blinded human raters
Authors: Jha Ashwani , Menozzi Elisa , Oyekan Rebecca , Latorre Anna , Mulroy Eoin , Schreglmann Sebastian R. , Stamate Cosmin , Daskalopoulos Ioannis , Kueppers Stefan , Luchini Marco , Rothwell John C. , Roussos George , Bhatia Kailash P. 
Published: December 2020

AbstractDigital assessments of motor severity could improve the sensitivity of clinical trials and personalise treatment in Parkinson’s disease (PD) but have yet to be widely adopted. Their ability to capture individual change across the heterogeneous motor presentations typical of PD remains inadequately tested against current clinical reference standards. We conducted a prospective, dual-site, crossover-randomised study to determine the ability of a 16-item smartphone-based assessment (the index test) to predict subitems from the Movement Disorder Society-Unified Parkinson’s Disease Rating Scale part III (MDS-UPDRS III) as assessed by three blinded clinical raters (the reference-standard). We analysed data from 60 subjects (990 smartphone tests, 2628 blinded video MDS-UPDRS III subitem ratings). Subject-level predictive performance was quantified as the leave-one-subject-out cross-validation (LOSO-CV) accuracy. A pre-specified analysis classified 70.3% (SEM 5.9%) of subjects into a similar category to any of three blinded clinical raters and was better than random (36.7%; SEM 4.3%) classification. Post hoc optimisation of classifier and feature selection improved performance further (78.7%, SEM 5.1%), although individual subtests were variable (range 53.2–97.0%). Smartphone-based measures of motor severity have predictive value at the subject level. Future studies should similarly mitigate against subjective and feature selection biases and assess performance across a range of motor features as part of a broader strategy to avoid overly optimistic performance estimates.
Data-driven computational prediction and experimental realization of exotic perovskite-related polar magnets
Authors: Han Yifeng , Wu Meixia , Gui Churen , Zhu Chuanhui , Sun Zhongxiong , Zhao Mei-Huan , Savina Aleksandra A. , Abakumov Artem M. , Wang Biao , Huang Feng , He LunHua , Chen Jie , Huang Qingzhen , Croft Mark , Ehrlich Steven , Khalid Syed , Deng Zheng , Jin Changqing , Grams Christoph P. , Hemberger Joachim , Wang Xueyun , Hong Jiawang , Adem Umut , Ye Meng , Dong Shuai , Li Man-Rong 
Published: December 2020

AbstractRational design of technologically important exotic perovskites is hampered by the insufficient geometrical descriptors and costly and extremely high-pressure synthesis, while the big-data driven compositional identification and precise prediction entangles full understanding of the possible polymorphs and complicated multidimensional calculations of the chemical and thermodynamic parameter space. Here we present a rapid systematic data-mining-driven approach to design exotic perovskites in a high-throughput and discovery speed of the A2BB’O6 family as exemplified in A3TeO6. The magnetoelectric polar magnet Co3TeO6, which is theoretically recognized and experimentally realized at 5 GPa from the six possible polymorphs, undergoes two magnetic transitions at 24 and 58 K and exhibits helical spin structure accompanied by magnetoelastic and magnetoelectric coupling. We expect the applied approach will accelerate the systematic and rapid discovery of new exotic perovskites in a high-throughput manner and can be extended to arbitrary applications in other families.
EANO guidelines on the diagnosis and treatment of diffuse gliomas of adulthood
Authors: Weller Michael , van den Bent Martin , Preusser Matthias , Le Rhun Emilie , Tonn Jörg C. , Minniti Giuseppe , Bendszus Martin , Balana Carmen , Chinot Olivier , Dirven Linda , French Pim , Hegi Monika E. , Jakola Asgeir S. , Platten Michael , Roth Patrick , Rudà Roberta , Short Susan , Smits Marion , Taphoorn Martin J. B. , von Deimling Andreas , Westphal Manfred , Soffietti Riccardo , Reifenberger Guido , Wick Wolfgang 
Published: December 2020

AbstractIn response to major changes in diagnostic algorithms and the publication of mature results from various large clinical trials, the European Association of Neuro-Oncology (EANO) recognized the need to provide updated guidelines for the diagnosis and management of adult patients with diffuse gliomas. Through these evidence-based guidelines, a task force of EANO provides recommendations for the diagnosis, treatment and follow-up of adult patients with diffuse gliomas. The diagnostic component is based on the 2016 update of the WHO Classification of Tumors of the Central Nervous System and the subsequent recommendations of the Consortium to Inform Molecular and Practical Approaches to CNS Tumour Taxonomy — Not Officially WHO (cIMPACT-NOW). With regard to therapy, we formulated recommendations based on the results from the latest practice-changing clinical trials and also provide guidance for neuropathological and neuroradiological assessment. In these guidelines, we define the role of the major treatment modalities of surgery, radiotherapy and systemic pharmacotherapy, covering current advances and cognizant that unnecessary interventions and expenses should be avoided. This document is intended to be a source of reference for professionals involved in the management of adult patients with diffuse gliomas, for patients and caregivers, and for health-care providers.
Quaternary functionalized mesoporous adsorbents for ultra-high kinetics of CO2 capture from air
Authors: Wang Tao , Wang Xinru , Hou Chenglong , Liu Jun 
Published: December 2020

AbstractObstacles to widespread deployments of direct air capture of CO2 (DAC) lie in high material and energy costs. By grafting quaternary ammonium (QA) functional group to mesoporous polymers with high surface area, a unique DAC adsorbent with moisture swing adsorption (MSA) ability and ultra-high kinetics was developed in this work. Functionalization is designed for efficient delivery of QA group through mesopores to active substitution sites. This achieved ultra-high kinetics adsorbent with half time of 2.9 min under atmospheric environment, is the highest kinetics value reported among DAC adsorbents. A cyclic adsorption capacity of 0.26 mmol g−1 is obtained during MSA process. Through adsorption thermodynamics, it is revealed that adsorbent with uniform cylindrical pore structure has higher functional group efficiency and CO2 capacity. Pore structure can also tune the MSA ability of adsorbent through capillary condensation of water inside its mesopores. The successful functionalization of mesoporous polymers with superb CO2 adsorption kinetics opens the door to facilitate DAC adsorbents for large-scale carbon capture deployments.