bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparison of breath-guards and face-masks on droplet spread in eye clinics
Authors: Newsom Richard , Pattison Chris , Lundgren Andrew , Robison Pauline , Quint Matthew , Amara Adam 
Published: December 2022

Abstract
Introduction
COVID-19 has impacted ophthalmic care delivery, with many units closed and several ophthalmologists catching COVID-19. Understanding droplet spread in clinical and training settings is paramount in maintaining productivity, while keeping patients and practitioners safe.

Objectives
We aimed to assess the effectiveness of a breath-guard and a face mask in reducing droplet spread within an eye clinic.

Methods
We performed a randomised trial of droplet spread using a fluorescein-based cough model to assess the efficacy of a ‘breath-guard’ and ‘face-mask’ to prevent the spread of droplets. The ‘cough’ spray was collected on calibrated paper targets. The sheets were photographed under blue light, with an orange filter on the camera; the position and size of the spots was measured with software originally developed for astronomy.
We performed 44 randomised coughs; 22 controls with no breath-guard or face-mask, 11 using breath-guard only and 11 with combined breath-guard and face-mask. We compared both the number of droplets detected and the area of drops on paper targets.

Results
The average number of droplets in the controls was 19,430 (SE 2691), the breath-guard group 80 (SE 19) droplets (P < 0.001); in the combined In the group the count was 5 (SE 2), a significant drop from shield only (P = 0.008). The mean areas of each target covered by spots for each group were 5.7 ± 0.857% (95% CI), 0.004 ± 0.000104% (95% CI) and 0.001 ± 0.0000627% (95% CI) respectively.

Conclusion
These results show that the breath-guard alone reduced the droplet count by 99.93%. Combining the breath-guard with a face-mask reduced the droplet count by over 99.98%. Breath-guards are widely used in clinics and this trial demonstrates that breath-guards with face-masks effectively block droplet spray.
Dual communities in spatial networks
Authors: Kaiser Franz , Böttcher Philipp C. , Ronellenfitsch Henrik , Latora Vito , Witthaut Dirk 
Published: December 2022

AbstractBoth human-made and natural supply systems, such as power grids and leaf venation networks, are built to operate reliably under changing external conditions. Many of these spatial networks exhibit community structures. Here, we show that a relatively strong connectivity between the parts of a network can be used to define a different class of communities: dual communities. We demonstrate that traditional and dual communities emerge naturally as two different phases of optimized network structures that are shaped by fluctuations and that they both suppress failure spreading, which underlines their importance in understanding the shape of real-world supply networks.
Membrane curvature governs the distribution of Piezo1 in live cells
Authors: Yang Shilong , Miao Xinwen , Arnold Steven , Li Boxuan , Ly Alan T. , Wang Huan , Wang Matthew , Guo Xiangfu , Pathak Medha M. , Zhao Wenting , Cox Charles D. , Shi Zheng 
Published: December 2022

AbstractPiezo1 is a bona fide mechanosensitive ion channel ubiquitously expressed in mammalian cells. The distribution of Piezo1 within a cell is essential for various biological processes including cytokinesis, cell migration, and wound healing. However, the underlying principles that guide the subcellular distribution of Piezo1 remain largely unexplored. Here, we demonstrate that membrane curvature serves as a key regulator of the spatial distribution of Piezo1 in the plasma membrane of living cells. Piezo1 depletes from highly curved membrane protrusions such as filopodia and enriches to nanoscale membrane invaginations. Quantification of the curvature-dependent sorting of Piezo1 directly reveals the in situ nano-geometry of the Piezo1-membrane complex. Piezo1 density on filopodia increases upon activation, independent of calcium, suggesting flattening of the channel upon opening. Consequently, the expression of Piezo1 inhibits filopodia formation, an effect that diminishes with channel activation.
A framework for clinical cancer subtyping from nucleosome profiling of cell-free DNA
Authors: Doebley Anna-Lisa , Ko Minjeong , Liao Hanna , Cruikshank A. Eden , Santos Katheryn , Kikawa Caroline , Hiatt Joseph B. , Patton Robert D. , De Sarkar Navonil , Collier Katharine A. , Hoge Anna C. H. , Chen Katharine , Zimmer Anat , Weber Zachary T. , Adil Mohamed , Reichel Jonathan B. , Polak Paz , Adalsteinsson Viktor A. , Nelson Peter S. , MacPherson David , Parsons Heather A. , Stover Daniel G. , Ha Gavin 
Published: December 2022

AbstractCell-free DNA (cfDNA) has the potential to inform tumor subtype classification and help guide clinical precision oncology. Here we develop Griffin, a framework for profiling nucleosome protection and accessibility from cfDNA to study the phenotype of tumors using as low as 0.1x coverage whole genome sequencing data. Griffin employs a GC correction procedure tailored to variable cfDNA fragment sizes, which generates a better representation of chromatin accessibility and improves the accuracy of cancer detection and tumor subtype classification. We demonstrate estrogen receptor subtyping from cfDNA in metastatic breast cancer. We predict estrogen receptor subtype in 139 patients with at least 5% detectable circulating tumor DNA with an area under the receive operator characteristic curve (AUC) of 0.89 and validate performance in independent cohorts (AUC = 0.96). In summary, Griffin is a framework for accurate tumor subtyping and can be generalizable to other cancer types for precision oncology applications.
Disorder-dominated quantum criticality in moiré bilayers
Authors: Tan Yuting , Tsang Pak Ki Henry , Dobrosavljević Vladimir 
Published: December 2022

AbstractMoiré bilayer materials have recently attracted much attention following the discovery of various correlated insulating states at specific band fillings. Here we discuss the metal-insulator transitions (MITs) that have been observed in the same devices, but at fillings far from the strongly correlated regime dominated by Mott-like physics, displaying many similarities to other examples of disorder-dominated MITs. We propose a minimal theoretical model describing the interplay of interactions and disorder, which is able to capture all the universal aspects of quantum criticality, as observed in experiments performed on several devices.
Cryo-EM structure of ssDNA bacteriophage ΦCjT23 provides insight into early virus evolution
Authors: Kejzar Nejc , Laanto Elina , Rissanen Ilona , Abrishami Vahid , Selvaraj Muniyandi , Moineau Sylvain , Ravantti Janne , Sundberg Lotta-Riina , Huiskonen Juha T. 
Published: December 2022

AbstractThe origin of viruses remains an open question. While lack of detectable sequence similarity hampers the analysis of distantly related viruses, structural biology investigations of conserved capsid protein structures facilitate the study of distant evolutionary relationships. Here we characterize the lipid-containing ssDNA temperate bacteriophage ΦCjT23, which infects Flavobacterium sp. (Bacteroidetes). We report ΦCjT23-like sequences in the genome of strains belonging to several Flavobacterium species. The virion structure determined by cryogenic electron microscopy reveals similarities to members of the viral kingdom Bamfordvirae that currently consists solely of dsDNA viruses with a major capsid protein composed of two upright β-sandwiches. The minimalistic structure of ΦCjT23 suggests that this phage serves as a model for the last common ancestor between ssDNA and dsDNA viruses in the Bamfordvirae. Both ΦCjT23 and the related phage FLiP infect Flavobacterium species found in several environments, suggesting that these types of viruses have a global distribution and a shared evolutionary origin. Detailed comparisons to related, more complex viruses not only expand our knowledge about this group of viruses but also provide a rare glimpse into early virus evolution.
A conserved population of MHC II-restricted, innate-like, commensal-reactive T cells in the gut of humans and mice
Authors: Hackstein Carl-Philipp , Costigan Dana , Drexhage Linnea , Pearson Claire , Bullers Samuel , Ilott Nicholas , Akther Hossain Delowar , Gu Yisu , FitzPatrick Michael E. B. , Harrison Oliver J. , Garner Lucy C. , Mann Elizabeth H. , Pandey Sumeet , Friedrich Matthias , Provine Nicholas M. , Uhlig Holm H. , Marchi Emanuele , Powrie Fiona , Klenerman Paul , Thornton Emily E. 
Published: December 2022

AbstractInteractions with commensal microbes shape host immunity on multiple levels and play a pivotal role in human health and disease. Tissue-dwelling, antigen-specific T cells are poised to respond to local insults, making their phenotype important in the relationship between host and microbes. Here we show that MHC-II restricted, commensal-reactive T cells in the colon of both humans and mice acquire transcriptional and functional characteristics associated with innate-like T cells. This cell population is abundant and conserved in the human and murine colon and endowed with polyfunctional effector properties spanning classic Th1- and Th17-cytokines, cytotoxic molecules, and regulators of epithelial homeostasis. T cells with this phenotype are increased in ulcerative colitis patients, and their presence aggravates pathology in dextran sodium sulphate-treated mice, pointing towards a pathogenic role in colitis. Our findings add to the expanding spectrum of innate-like immune cells positioned at the frontline of intestinal immune surveillance, capable of acting as sentinels of microbes and the local cytokine milieu.
Genetic features and therapeutic relevance of emergent circulating tumor DNA alterations in refractory non-colorectal gastrointestinal cancers
Authors: Hsiehchen David , Bucheit Leslie , Yang Dong , Beg Muhammad Shaalan , Lim Mir , Lee Sunyoung S. , Kasi Pashtoon Murtaza , Kaseb Ahmed O. , Zhu Hao 
Published: December 2022

AbstractAcquired resistance to systemic treatments is inevitable in most cancers, but the genetic basis for this in many cancer types has remained elusive due to constraints in obtaining tissue specimens longitudinally. In the management of gastrointestinal cancers, molecular profiling is conventionally performed at a single time point, although serial evaluations may yield biological insights that inform treatment decisions. We characterize genetic changes in serial liquid biopsies which provide real-time snapshots of tumor genetics and heterogeneity in refractory non-colorectal gastrointestinal cancers, and determine the clinical utility of repeat circulating tumor DNA (ctDNA) testing. In a national cohort of 449 patients with pancreatic, biliary, esophagogastric, and hepatocellular cancers, resistance to conventional therapies is broadly associated with tumor evolution. Emergent ctDNA alterations only detectable at progression occurs in 63% of patients and are frequently associated with treatment actionability. Tumor mutation burden is dynamic in cancers undergoing treatment, but is not associated with time to progression. Objective tumor responses in a case series of patients receiving treatment matched to emergent alterations show that repeat liquid biopsies may have clinical benefit by expanding treatment options in advanced gastrointestinal cancers.
Retrotransposon instability dominates the acquired mutation landscape of mouse induced pluripotent stem cells
Authors: Gerdes Patricia , Lim Sue Mei , Ewing Adam D. , Larcombe Michael R. , Chan Dorothy , Sanchez-Luque Francisco J. , Walker Lucinda , Carleton Alexander L. , James Cini , Knaupp Anja S. , Carreira Patricia E. , Nefzger Christian M. , Lister Ryan , Richardson Sandra R. , Polo Jose M. , Faulkner Geoffrey J. 
Published: December 2022

AbstractInduced pluripotent stem cells (iPSCs) can in principle differentiate into any cell of the body, and have revolutionized biomedical research and regenerative medicine. Unlike their human counterparts, mouse iPSCs (miPSCs) are reported to silence transposable elements and prevent transposable element-mediated mutagenesis. Here we apply short-read or Oxford Nanopore Technologies long-read genome sequencing to 38 bulk miPSC lines reprogrammed from 10 parental cell types, and 18 single-cell miPSC clones. While single nucleotide variants and structural variants restricted to miPSCs are rare, we find 83 de novo transposable element insertions, including examples intronic to Brca1 and Dmd. LINE-1 retrotransposons are profoundly hypomethylated in miPSCs, beyond other transposable elements and the genome overall, and harbor alternative protein-coding gene promoters. We show that treatment with the LINE-1 inhibitor lamivudine does not hinder reprogramming and efficiently blocks endogenous retrotransposition, as detected by long-read genome sequencing. These experiments reveal the complete spectrum and potential significance of mutations acquired by miPSCs.
Nationwide geospatial analysis of county racial and ethnic composition and public drinking water arsenic and uranium
Authors: Martinez-Morata Irene , Bostick Benjamin C. , Conroy-Ben Otakuye , Duncan Dustin T. , Jones Miranda R. , Spaur Maya , Patterson Kevin P. , Prins Seth J. , Navas-Acien Ana , Nigra Anne E. 
Published: December 2022

AbstractThere is no safe level of exposure to inorganic arsenic or uranium, yet recent studies identified sociodemographic and regional inequalities in concentrations of these frequently detected contaminants in public water systems across the US. We analyze the county-level association between racial/ethnic composition and public water arsenic and uranium concentrations from 2000–2011 using geospatial models. We find that higher proportions of Hispanic/Latino and American Indian/Alaskan Native residents are associated with significantly higher arsenic and uranium concentrations. These associations differ in magnitude and direction across regions; higher proportions of non-Hispanic Black residents are associated with higher arsenic and uranium in regions where concentrations of these contaminants are high. The findings from this nationwide geospatial analysis identifying racial/ethnic inequalities in arsenic and uranium concentrations in public drinking water across the US can advance environmental justice initiatives by informing regulatory action and financial and technical support to protect communities of color.
Inverse design of 3D reconfigurable curvilinear modular origami structures using geometric and topological reconstructions
Authors: Xiao Kai , Liang Zihe , Zou Bihui , Zhou Xiang , Ju Jaehyung 
Published: December 2022

AbstractThe recent development of modular origami structures has ushered in an era for active metamaterials with multiple degrees of freedom (multi-DOF). Notably, no systematic inverse design approach for 3D curvilinear modular origami structures has been reported. Moreover, very few modular origami topologies have been studied to design active metamaterials with multi-DOF. Herein, we develop an inverse design method for constructing 3D reconfigurable architected structures — we synthesize modular origami structures whose unit cells can be volumetrically mapped into a prescribed 3D curvilinear shape followed by volumetric shrinkage to construct modules. After modification of the tubular geometry, we search through all the possible geometric and topological combinations of the modular origami structures to attain the target mobility using a topological reconstruction of modules. Our inverse design using geometric and topological reconstructions can provide an effective solution to construct 3D curvilinear reconfigurable structures with multi-DOF. Our work opens a path toward 3D reconfigurable systems based on volumetric inverse design, such as 3D active metamaterials and 3D morphing devices for automotive, aerospace, and biomedical engineering applications.
ERK-mediated NELF-A phosphorylation promotes transcription elongation of immediate-early genes by releasing promoter-proximal pausing of RNA polymerase II
Authors: Ohe Seina , Kubota Yuji , Yamaguchi Kiyoshi , Takagi Yusuke , Nashimoto Junichiro , Kozuka-Hata Hiroko , Oyama Masaaki , Furukawa Yoichi , Takekawa Mutsuhiro 
Published: December 2022

AbstractGrowth factor-induced, ERK-mediated induction of immediate-early genes (IEGs) is crucial for cell growth and tumorigenesis. Although IEG expression is mainly regulated at the level of transcription elongation by RNA polymerase-II (Pol-II) promoter-proximal pausing and its release, the role of ERK in this process remains unknown. Here, we identified negative elongation factor (NELF)-A as an ERK substrate. Upon growth factor stimulation, ERK phosphorylates NELF-A, which dissociates NELF from paused Pol-II at the promoter-proximal regions of IEGs, allowing Pol-II to resume elongation and produce full-length transcripts. Furthermore, we found that in cancer cells, PP2A efficiently dephosphorylates NELF-A, thereby preventing aberrant IEG expression induced by ERK-activating oncogenes. However, when PP2A inhibitor proteins are overexpressed, as is frequently observed in cancers, decreased PP2A activity combined with oncogene-mediated ERK activation conspire to induce NELF-A phosphorylation and IEG upregulation, resulting in tumor progression. Our data delineate previously unexplored roles of ERK and PP2A inhibitor proteins in carcinogenesis.
Graph-based autoencoder integrates spatial transcriptomics with chromatin images and identifies joint biomarkers for Alzheimer’s disease
Authors: Zhang Xinyi , Wang Xiao , Shivashankar G. V. , Uhler Caroline 
Published: December 2022

AbstractTissue development and disease lead to changes in cellular organization, nuclear morphology, and gene expression, which can be jointly measured by spatial transcriptomic technologies. However, methods for jointly analyzing the different spatial data modalities in 3D are still lacking. We present a computational framework to integrate Spatial Transcriptomic data using over-parameterized graph-based Autoencoders with Chromatin Imaging data (STACI) to identify molecular and functional alterations in tissues. STACI incorporates multiple modalities in a single representation for downstream tasks, enables the prediction of spatial transcriptomic data from nuclear images in unseen tissue sections, and provides built-in batch correction of gene expression and tissue morphology through over-parameterization. We apply STACI to analyze the spatio-temporal progression of Alzheimer’s disease and identify the associated nuclear morphometric and coupled gene expression features. Collectively, we demonstrate the importance of characterizing disease progression by integrating multiple data modalities and its potential for the discovery of disease biomarkers.
Setd2 supports GATA3+ST2+ thymic-derived Treg cells and suppresses intestinal inflammation
Authors: Ding Zhaoyun , Cai Ting , Tang Jupei , Sun Hanxiao , Qi Xinyi , Zhang Yunpeng , Ji Yan , Yuan Liyun , Chang Huidan , Ma Yanhui , Zhou Hong , Li Li , Sheng Huiming , Qiu Ju 
Published: December 2022

AbstractTreg cells acquire distinct transcriptional properties to suppress specific inflammatory responses. Transcription characteristics of Treg cells are regulated by epigenetic modifications, the mechanism of which remains obscure. Here, we report that Setd2, a histone H3K36 methyltransferase, is important for the survival and suppressive function of Treg cells, especially those from the intestine. Setd2 supports GATA3+ST2+ intestinal thymic-derived Treg (tTreg) cells by facilitating the expression and reciprocal relationship of GATA3 and ST2 in tTreg cells. IL-33 preferentially boosts Th2 cells rather than GATA3+ Treg cells in Foxp3Cre-YFPSetd2 flox/flox mice, corroborating the constraint of Th2 responses by Setd2 expression in Treg cells. SETD2 sustains GATA3 expression in human Treg cells, and SETD2 expression is increased in Treg cells from human colorectal cancer tissues. Epigenetically, Setd2 regulates the transcription of target genes (including Il1rl1) by modulating the activity of promoters and intragenic enhancers where H3K36me3 is typically deposited. Our findings provide mechanistic insights into the regulation of Treg cells and intestinal immunity by Setd2.
Apical anchorage and stabilization of subpellicular microtubules by apical polar ring ensures Plasmodium ookinete infection in mosquito
Authors: Qian Pengge , Wang Xu , Guan Cuirong , Fang Xin , Cai Mengya , Zhong Chuan-qi , Cui Yong , Li Yanbin , Yao Luming , Cui Huiting , Jiang Kai , Yuan Jing 
Published: December 2022

AbstractMorphogenesis of many protozoans depends on a polarized establishment of cortical cytoskeleton containing the subpellicular microtubules (SPMTs), which are apically nucleated and anchored by the apical polar ring (APR). In malaria parasite Plasmodium, APR emerges in the host-invading stages, including the ookinete for mosquito infection. So far, the fine structure and molecular components of APR as well as the underlying mechanism of APR-mediated apical positioning of SPMTs are largely unknown. Here, we resolve an unprecedented APR structure composed of a top ring plus approximate 60 radiating spines. We report an APR-localizing and SPMT-binding protein APR2. APR2 disruption impairs ookinete morphogenesis and gliding motility, leading to Plasmodium transmission failure in mosquitoes. The APR2-deficient ookinetes display defective apical anchorage of APR and SPMT due to the impaired integrity of APR. Using protein proximity labeling, we obtain a Plasmodium ookinete APR proteome and validate ten undescribed APR proteins. Among them, APRp2 and APRp4 directly interact with APR2 and also mediate the apical anchorage of SPMTs. This study sheds light on the molecular basis of APR in the organization of Plasmodium ookinete SPMTs.
Many-body localization in the infinite-interaction limit and the discontinuous eigenstate phase transition
Authors: Chen Chun , Chen Yan , Wang Xiaoqun 
Published: December 2022

AbstractWe study many-body localization (MBL) in a spin-chain model mimicking the Rydberg-blockade quantum simulator with infinite-strength projection and moderate quasiperiodic modulation. Employing exact diagonalization, Krylov-typicality technique, and time-evolving block decimation, we identify evidence for a constrained MBL phase stabilized by a pure quasirandom transverse field. Intriguingly, the constrained MBL transition may embody a discontinuous eigenstate phase transition, whose discontinuity nature significantly suppresses finite-size drifts that plague most numerical studies of conventional MBL transition. Through quantum dynamics, we find that rotating the modulated field from parallel toward perpendicular to the projection axis induces an eigenstate transition between diagonal and constrained MBL phases. The entanglement-entropy growth in constrained MBL follows a double-log form, whereas it changes to a power law in approaching the diagonal limit. By unveiling confined nonlocal effects in integrals of motion of constrained MBL, we show this insulating state is not a many-body Anderson insulator. Our predictions are testable in Rydberg experiments.