bluuebunny/crossref_metadata_2025_split huggingface dataset:
Removal of the rate table: MEMS gyrocompass with virtual maytagging
Authors: Miao Tongqiao , Li Qingsong , Chen Liangqian , Li Junjian , Hu Xiaoping , Wu Xuezhong , Wu Wenqi , Xiao Dingbang 
Published: November 2023

AbstractHigh-performance micro-electro-mechanical system (MEMS) gyrocompasses for north-finding systems have been very popular for decades. In this paper, a MEMS north-finding system (NFS) based on virtual maytagging (VM) is presented for the first time. In stark contrast to previous schemes of MEMS-based NFSs (e.g., carouseling, maytagging) and the abandoning rate table, we developed a honeycomb disk resonator gyroscope (HDRG) and two commercial accelerometers for azimuth detection. Instead of the physical rotation of the integrated turntable in traditional NFSs, the vibratory working modes of the HDRG are rotated periodically with electronic control to reduce the uncertainty in the azimuth. After systematically analyzing the principle of NFSs with VM, we designed tests to verify the practicability at the sensor level. A bias instability of 0.0078°/h can be obtained during one day with VM in an HDRG. We also implemented comparative north-finding experiments to further check our strategy at the system level. The accuracy in the azimuth can reach 0.204° for 5 min at 28.2° latitude with VM and 0.172° with maytagging. The results show that without any mechanical turning parts, VM technology makes it possible to develop high-precision handheld MEMS NFSs.
Combined in vitro/in vivo genome-wide CRISPR screens in triple negative breast cancer identify cancer stemness regulators in paclitaxel resistance
Authors: Yan Gang , Dai Meiou , Poulet Sophie , Wang Ni , Boudreault Julien , Daliah Girija , Ali Suhad , Lebrun Jean-Jacques 
Published: November 2023

AbstractTriple negative breast cancer (TNBC) is defined as lacking the expressions of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2). TNBC patients exhibit relatively poor clinical outcomes due to lack of molecular markers for targeted therapies. As such chemotherapy often remains the only systemic treatment option for these patients. While chemotherapy can initially help shrink TNBC tumor size, patients eventually develop resistance to drug, leading to tumor recurrence. We report a combined in vitro/in vivo genome-wide CRISPR synthetic lethality screening approach in a relevant TNBC cell line model to identify several targets responsible for the chemotherapy drug, paclitaxel resistance. Computational analysis integrating in vitro and in vivo data identified a set of genes, for which specific loss-of-function deletion enhanced paclitaxel resistance in TNBC. We found that several of these genes (ATP8B3, FOXR2, FRG2, HIST1H4A) act as cancer stemness negative regulators. Finally, using in vivo orthotopic transplantation TNBC models we showed that FRG2 gene deletion reduced paclitaxel efficacy and promoted tumor metastasis, while increasing FRG2 expression by means of CRISPR activation efficiently sensitized TNBC tumors to paclitaxel treatment and inhibited their metastatic abilities. In summary, the combined in vitro/in vivo genome-wide CRISPR screening approach proved effective as a tool to identify novel regulators of paclitaxel resistance/sensitivity and highlight the FRG2 gene as a potential therapeutical target overcoming paclitaxel resistance in TNBC.
Mesenchymal stem cells under epigenetic control – the role of epigenetic machinery in fate decision and functional properties
Authors: Walewska Alicja , Janucik Adrian , Tynecka Marlena , Moniuszko Marcin , Eljaszewicz Andrzej 
Published: November 2023

AbstractMesenchymal stem cells (mesenchymal stromal cells, MSC) are multipotent stem cells that can differentiate into cells of at least three mesodermal lineages, namely adipocytes, osteoblasts, and chondrocytes, and have potent immunomodulatory properties. Epigenetic modifications are critical regulators of gene expression and cellular differentiation of mesenchymal stem cells (MSCs). Epigenetic machinery controls MSC differentiation through direct modifications to DNA and histones. Understanding the role of epigenetic machinery in MSC is crucial for the development of effective cell-based therapies for degenerative and inflammatory diseases. In this review, we summarize the current understanding of the role of epigenetic control of MSC differentiation and immunomodulatory properties.
PD-1 signaling negatively regulates the common cytokine receptor γ chain via MARCH5-mediated ubiquitination and degradation to suppress anti-tumor immunity
Authors: Liu Rui , Zeng Lin-Wen , Li Hui-Fang , Shi Jun-Ge , Zhong Bo , Shu Hong-Bing , Li Shu 
Published: November 2023

AbstractCombination therapy with PD-1 blockade and IL-2 substantially improves anti-tumor efficacy comparing to monotherapy. The underlying mechanisms responsible for the synergistic effects of the combination therapy remain enigmatic. Here we show that PD-1 ligation results in BATF-dependent transcriptional induction of the membrane-associated E3 ubiquitin ligase MARCH5, which mediates K27-linked polyubiquitination and lysosomal degradation of the common cytokine receptor γ chain (γc). PD-1 ligation also activates SHP2, which dephosphorylates γcY357, leading to impairment of γc family cytokine-triggered signaling. Conversely, PD-1 blockade restores γc level and activity, thereby sensitizing CD8+ T cells to IL-2. We also identified Pitavastatin Calcium as an inhibitor of MARCH5, which combined with PD-1 blockade and IL-2 significantly improves the efficacy of anti-tumor immunotherapy in mice. Our findings uncover the mechanisms by which PD-1 signaling antagonizes γc family cytokine-triggered immune activation and demonstrate that the underlying mechanisms can be exploited for increased efficacy of combination immunotherapy of cancer.
A randomised Phase IIa trial of amine oxidase copper-containing 3 (AOC3) inhibitor BI 1467335 in adults with non-alcoholic steatohepatitis
Authors: Newsome Philip N. , Sanyal Arun J. , Neff Guy , Schattenberg Jörn M. , Ratziu Vlad , Ertle Judith , Link Jasmin , Mackie Alison , Schoelch Corinna , Lawitz Eric ,   BI 1467335 NASH Phase IIa trial team
Published: November 2023

AbstractNon-alcoholic steatohepatitis (NASH) is a progressive, inflammatory liver disease with no approved pharmacological treatment. This Phase IIa, double-blind, placebo-controlled, multicentre trial (ClinicalTrials.gov: NCT03166735) investigated pharmacodynamics and safety of BI 1467335, an amine oxidase copper-containing 3 (AOC3) inhibitor, in adults with NASH from Europe and North America. Participants from 44 centres across the US, Germany, Spain, Belgium, the UK, Netherlands, Canada, France and Ireland were randomised (2:1:1:1:2; 27 July 2017 to 14 June 2019) to daily oral BI 1467335 1 mg (n = 16), 3 mg (n = 16), 6 mg (n = 17), 10 mg (n = 32) or placebo (n = 32) for 12 weeks, with follow-up to Week 16. Primary endpoint was AOC3 activity relative to baseline (%), 24 hours post-dose after 12 weeks’ treatment. Secondary biomarker endpoints included changes from baseline at Week 12 in alanine aminotransferase (ALT) and caspase-cleaved cytokeratin 18 (CK-18 caspase). Mean AOC3 activities relative to baseline at Week 12: 90.4% (placebo; n = 32), 26.5% (1 mg; n = 16), 10.4% (3 mg; n = 16), 5.0% (6 mg; n = 16), 3.3% (10 mg; n = 32). These changes indicated that BI 1467335 dose-dependently inhibited AOC3 activity; ≥3 mg doses achieved >80% inhibition ( < 20% activity) at Week 4. At Week 12 following doses of BI 1467335 ≥ 3 mg, ALT and CK-18 caspase decreased dose-dependently. All tested BI 1467335 doses were well tolerated, with no clinically relevant treatment-emergent safety signals. BI 1467335 strongly inhibited AOC3 in participants with NASH, with doses ≥3 mg dose-dependently reducing the levels of liver injury biomarkers, ALT and CK-18. This trial was registered with ClinicalTrials.gov (NCT03166735) and the European Union Drug Regulating Authorities Clinical Trials Database (EudraCT 2016-000499-83).
Validation of MSIntuit as an AI-based pre-screening tool for MSI detection from colorectal cancer histology slides
Authors: Saillard Charlie , Dubois Rémy , Tchita Oussama , Loiseau Nicolas , Garcia Thierry , Adriansen Aurélie , Carpentier Séverine , Reyre Joelle , Enea Diana , von Loga Katharina , Kamoun Aurélie , Rossat Stéphane , Wiscart Corentin , Sefta Meriem , Auffret Michaël , Guillou Lionel , Fouillet Arnaud , Kather Jakob Nikolas , Svrcek Magali 
Published: November 2023

AbstractMismatch Repair Deficiency (dMMR)/Microsatellite Instability (MSI) is a key biomarker in colorectal cancer (CRC). Universal screening of CRC patients for MSI status is now recommended, but contributes to increased workload for pathologists and delayed therapeutic decisions. Deep learning has the potential to ease dMMR/MSI testing and accelerate oncologist decision making in clinical practice, yet no comprehensive validation of a clinically approved tool has been conducted. We developed MSIntuit, a clinically approved artificial intelligence (AI) based pre-screening tool for MSI detection from haematoxylin-eosin (H&E) stained slides. After training on samples from The Cancer Genome Atlas (TCGA), a blind validation is performed on an independent dataset of 600 consecutive CRC patients. Inter-scanner reliability is studied by digitising each slide using two different scanners. MSIntuit yields a sensitivity of 0.96–0.98, a specificity of 0.47-0.46, and an excellent inter-scanner agreement (Cohen’s κ: 0.82). By reaching high sensitivity comparable to gold standard methods while ruling out almost half of the non-MSI population, we show that MSIntuit can effectively serve as a pre-screening tool to alleviate MSI testing burden in clinical practice.
Nodal band-off-diagonal superconductivity in twisted graphene superlattices
Authors: Christos Maine , Sachdev Subir , Scheurer Mathias S. 
Published: November 2023

AbstractThe superconducting state and mechanism are among the least understood phenomena in twisted graphene systems. Recent tunneling experiments indicate a transition between nodal and gapped pairing with electron filling, which is not naturally understood within current theory. We demonstrate that the coexistence of superconductivity and flavor polarization leads to pairing channels that are guaranteed by symmetry to be entirely band-off-diagonal, with a variety of consequences: most notably, the pairing invariant under all symmetries can have Bogoliubov Fermi surfaces in the superconducting state with protected nodal lines, or may be fully gapped, depending on parameters, and the band-off-diagonal chiralp-wave state exhibits transitions between gapped and nodal regions upon varying the doping. We demonstrate that band-off-diagonal pairing can be the leading state when only phonons are considered, and is also uniquely favored by fluctuations of a time-reversal-symmetric intervalley coherent order motivated by recent experiments. Consequently, band-off-diagonal superconductivity allows for the reconciliation of several key experimental observations in graphene moiré systems.
Dual function of OmpM as outer membrane tether and nutrient uptake channel in diderm Firmicutes
Authors: Silale Augustinas , Zhu Yiling , Witwinowski Jerzy , Smith Robert E. , Newman Kahlan E. , Bhamidimarri Satya P. , Baslé Arnaud , Khalid Syma , Beloin Christophe , Gribaldo Simonetta , van den Berg Bert 
Published: November 2023

AbstractThe outer membrane (OM) in diderm, or Gram-negative, bacteria must be tethered to peptidoglycan for mechanical stability and to maintain cell morphology. Most diderm phyla from the Terrabacteria group have recently been shown to lack well-characterised OM attachment systems, but instead have OmpM, which could represent an ancestral tethering system in bacteria. Here, we have determined the structure of the most abundant OmpM protein from Veillonella parvula (diderm Firmicutes) by single particle cryogenic electron microscopy. We also characterised the channel properties of the transmembrane β-barrel of OmpM and investigated the structure and PG-binding properties of its periplasmic stalk region. Our results show that OM tethering and nutrient acquisition are genetically linked in V. parvula, and probably other diderm Terrabacteria. This dual function of OmpM may have played a role in the loss of the OM in ancestral bacteria and the emergence of monoderm bacterial lineages.
Tracing cancer evolution and heterogeneity using Hi-C
Authors: Erdmann-Pham Dan Daniel , Batra Sanjit Singh , Turkalo Timothy K. , Durbin James , Blanchette Marco , Yeh Iwei , Shain Hunter , Bastian Boris C. , Song Yun S. , Rokhsar Daniel S. , Hockemeyer Dirk 
Published: November 2023

AbstractChromosomal rearrangements can initiate and drive cancer progression, yet it has been challenging to evaluate their impact, especially in genetically heterogeneous solid cancers. To address this problem we developed HiDENSEC, a new computational framework for analyzing chromatin conformation capture in heterogeneous samples that can infer somatic copy number alterations, characterize large-scale chromosomal rearrangements, and estimate cancer cell fractions. After validating HiDENSEC with in silico and in vitro controls, we used it to characterize chromosome-scale evolution during melanoma progression in formalin-fixed tumor samples from three patients. The resulting comprehensive annotation of the genomic events includes copy number neutral translocations that disrupt tumor suppressor genes such as NF1, whole chromosome arm exchanges that result in loss of CDKN2A, and whole-arm copy-number neutral loss of homozygosity involving PTEN. These findings show that large-scale chromosomal rearrangements occur throughout cancer evolution and that characterizing these events yields insights into drivers of melanoma progression.
Evolutionary design of explainable algorithms for biomedical image segmentation
Authors: Cortacero Kévin , McKenzie Brienne , Müller Sabina , Khazen Roxana , Lafouresse Fanny , Corsaut Gaëlle , Van Acker Nathalie , Frenois François-Xavier , Lamant Laurence , Meyer Nicolas , Vergier Béatrice , Wilson Dennis G. , Luga Hervé , Staufer Oskar , Dustin Michael L. , Valitutti Salvatore , Cussat-Blanc Sylvain 
Published: November 2023

AbstractAn unresolved issue in contemporary biomedicine is the overwhelming number and diversity of complex images that require annotation, analysis and interpretation. Recent advances in Deep Learning have revolutionized the field of computer vision, creating algorithms that compete with human experts in image segmentation tasks. However, these frameworks require large human-annotated datasets for training and the resulting “black box” models are difficult to interpret. In this study, we introduce Kartezio, a modular Cartesian Genetic Programming-based computational strategy that generates fully transparent and easily interpretable image processing pipelines by iteratively assembling and parameterizing computer vision functions. The pipelines thus generated exhibit comparable precision to state-of-the-art Deep Learning approaches on instance segmentation tasks, while requiring drastically smaller training datasets. This Few-Shot Learning method confers tremendous flexibility, speed, and functionality to this approach. We then deploy Kartezio to solve a series of semantic and instance segmentation problems, and demonstrate its utility across diverse images ranging from multiplexed tissue histopathology images to high resolution microscopy images. While the flexibility, robustness and practical utility of Kartezio make this fully explicable evolutionary designer a potential game-changer in the field of biomedical image processing, Kartezio remains complementary and potentially auxiliary to mainstream Deep Learning approaches.
Eco-evolutionary feedbacks in the human gut microbiome
Authors: Good Benjamin H. , Rosenfeld Layton B. 
Published: November 2023

AbstractGut microbiota can evolve within their hosts on human-relevant timescales, but little is known about how these changes influence (or are influenced by) the composition of their local community. Here, by combining ecological and evolutionary analyses of a large cohort of human gut metagenomes, we show that the short-term evolution of the microbiota is linked with shifts in its ecological structure. These correlations are not simply explained by expansions of the evolving species, and often involve additional fluctuations in distantly related taxa. We show that similar feedbacks naturally emerge in simple resource competition models, even in the absence of cross-feeding or predation. These results suggest that the structure and function of host microbiota may be shaped by their local evolutionary history, which could have important implications for personalized medicine and microbiome engineering.
Microbiome and metabolome features in inflammatory bowel disease via multi-omics integration analyses across cohorts
Authors: Ning Lijun , Zhou Yi-Lu , Sun Han , Zhang Youwei , Shen Chaoqin , Wang Zhenhua , Xuan Baoqin , Zhao Ying , Ma Yanru , Yan Yuqing , Tong Tianying , Huang Xiaowen , Hu Muni , Zhu Xiaoqiang , Ding Jinmei , Zhang Yue , Cui Zhe , Fang Jing-Yuan , Chen Haoyan , Hong Jie 
Published: November 2023

AbstractThe perturbations of the gut microbiota and metabolites are closely associated with the progression of inflammatory bowel disease (IBD). However, inconsistent findings across studies impede a comprehensive understanding of their roles in IBD and their potential as reliable diagnostic biomarkers. To address this challenge, here we comprehensively analyze 9 metagenomic and 4 metabolomics cohorts of IBD from different populations. Through cross-cohort integrative analysis (CCIA), we identify a consistent characteristic of commensal gut microbiota. Especially, three bacteria, namely Asaccharobacter celatus, Gemmiger formicilis, and Erysipelatoclostridium ramosum, which are rarely reported in IBD. Metagenomic functional analysis reveals that essential gene of Two-component system pathway, linked to fecal calprotectin, are implicated in IBD. Metabolomics analysis shows 36 identified metabolites with significant differences, while the roles of these metabolites in IBD are still unknown. To further elucidate the relationship between gut microbiota and metabolites, we construct multi-omics biological correlation (MOBC) maps, which highlights gut microbial biotransformation deficiencies and significant alterations in aminoacyl-tRNA synthetases. Finally, we identify multi-omics biomarkers for IBD diagnosis, validated across multiple global cohorts (AUROC values ranging from 0.92 to 0.98). Our results offer valuable insights and a significant resource for developing mechanistic hypotheses on host-microbiome interactions in IBD.
Bioinspired thermadapt shape-memory polymer with light-induced reversible fluorescence for rewritable 2D/3D-encoding information carriers
Authors: Huang Jinhui , Jiang Yue , Chen Qiuyu , Xie Hui , Zhou Shaobing 
Published: November 2023

AbstractFluorescent materials have attracted widespread attention for information encryption owing to their stimuli-responsive color-shifting. However, the 2D encoding of fluorescent images poses a risk of information leakage. Herein, inspired by the mimic octopus capable of camouflage by changing colors and shapes, we develop a thermadapt shape-memory fluorescent film (TSFF) for integrating 2D/3D encoding in one system. The TSFF is based on anthracene group with reversible photo-cross-linking and poly (ethylene-co-vinyl acetate) network with thermadapt shape-memory properties. The reversible photo-cross-linking of anthracene is accompanied by repeatable fluorescence-shifting and enables rewritable 2D encoding. Meanwhile, the thermadapt shape-memory properties not only enables the reconfiguration of the permanent shape for creating and erasing 3D patterns, i.e., rewritable 3D information, but also facilitates recoverable shape programming for 3D encoding. This rewritable 2D/3D encoding strategy can enhance information security because only designated inspectors can decode the information by providing sequential heating for shape recovery and UV exposure. Overall, TSFF capable of rewritable 2D/3D encoding will inspire the design of smart materials for high-security information carriers.
Structure of a heteropolymeric type 4 pilus from a monoderm bacterium
Authors: Anger Robin , Pieulle Laetitia , Shahin Meriam , Valette Odile , Le Guenno Hugo , Kosta Artemis , Pelicic Vladimir , Fronzes Rémi 
Published: November 2023

AbstractType 4 pili (T4P) are important virulence factors, which belong to a superfamily of nanomachines ubiquitous in prokaryotes, called type 4 filaments (T4F). T4F are defined as helical polymers of type 4 pilins. Recent advances in cryo-electron microscopy (cryo-EM) led to structures of several T4F, revealing that the long N-terminal α-helix (α1) – the trademark of pilins – packs in the centre of the filaments to form a hydrophobic core. In diderm bacteria – all available bacterial T4F structures are from diderm species – a portion of α1 is melted (unfolded). Here we report that this architecture is conserved in phylogenetically distant monoderm species by determining the structure of Streptococcus sanguinis T4P. Our 3.7 Å resolution cryo-EM structure of S. sanguinis heteropolymeric T4P and the resulting full atomic model including all minor pilins highlight universal features of bacterial T4F and have widespread implications in understanding T4F biology.
Long-term sea level rise modeling of a basin-tidal inlet system reveals sediment sinks
Authors: Hanegan Kevin C. , FitzGerald Duncan M. , Georgiou Ioannis Y. , Hughes Zoe J. 
Published: November 2023

AbstractMuch of the world’s population lives close to coastlines and this proximity is becoming increasingly impactful because of sea-level rise (SLR). Barrier islands and backbarrier saltmarshes, which comprise >10% of these coasts, are particularly susceptible. To better understand this risk, we model backbarrier morphologic and hydrodynamic evolution over a 200-year period of SLR, incorporating an erodible bed and a range of grain sizes. Here, we show that reduction in intertidal area creates negative feedback, shifting transport of coarse sediment (silt and sand) through the inlet from net export to net import. Imposing a modest marsh vertical accretion rate decreases the period of silt and sand import to 40 years (years 90 to 130) before being exported again. Clay is continuously exported thereby decreasing inorganic deposition on marshes and threatening their sustainability. Simulated marsh loss increases tidal prism and the volume of sand contained in ebb deltas, depleting coastal sand resources.
Realizing a deep reinforcement learning agent for real-time quantum feedback
Authors: Reuer Kevin , Landgraf Jonas , Fösel Thomas , O’Sullivan James , Beltrán Liberto , Akin Abdulkadir , Norris Graham J. , Remm Ants , Kerschbaum Michael , Besse Jean-Claude , Marquardt Florian , Wallraff Andreas , Eichler Christopher 
Published: November 2023

AbstractRealizing the full potential of quantum technologies requires precise real-time control on time scales much shorter than the coherence time. Model-free reinforcement learning promises to discover efficient feedback strategies from scratch without relying on a description of the quantum system. However, developing and training a reinforcement learning agent able to operate in real-time using feedback has been an open challenge. Here, we have implemented such an agent for a single qubit as a sub-microsecond-latency neural network on a field-programmable gate array (FPGA). We demonstrate its use to efficiently initialize a superconducting qubit and train the agent based solely on measurements. Our work is a first step towards adoption of reinforcement learning for the control of quantum devices and more generally any physical device requiring low-latency feedback.