bluuebunny/crossref_metadata_2025_split huggingface dataset:
Red/processed meat consumption and non-cancer-related outcomes in humans: umbrella review
Authors: Zhang Xingxia , Liang Shiqi , Chen Xinrong , Yang Jie , Zhou Yong , Du Liang , Li Ka 
Published: December 2022

AbstractThe associations of red/processed meat consumption and cancer-related health outcomes have been well discussed. The umbrella review aimed to summarise the associations of red/processed meat consumption and various non-cancer-related outcomes in humans. We systematically searched the systematic reviews and meta-analyses of associations between red/processed meat intake and health outcomes from PubMed, Embase, Web of Science and the Cochrane Library databases. The umbrella review has been registered in PROSPERO (CRD 42021218568). A total of 40 meta-analyses were included. High consumption of red meat, particularly processed meat, was associated with a higher risk of all-cause mortality, CVD and metabolic outcomes. Dose–response analysis revealed that an additional 100 g/d red meat intake was positively associated with a 17 % increased risk of type 2 diabetes mellitus (T2DM), 15 % increased risk of CHD, 14 % of hypertension and 12 % of stroke. The highest dose–response/50 g increase in processed meat consumption at 95 % confident levels was 1·37, 95 % CI (1·22, 1·55) for T2DM, 1·27, 95 % CI (1·09, 1·49) for CHD, 1·17, 95 % CI (1·02, 1·34) for stroke, 1·15, 95 % CI (1·11, 1·19) for all-cause mortality and 1·08, 95 % CI (1·02, 1·14) for heart failure. In addition, red/processed meat intake was associated with several other health-related outcomes. Red and processed meat consumption seems to be more harmful than beneficial to human health in this umbrella review. It is necessary to take the impacts of red/processed meat consumption on non-cancer-related outcomes into consideration when developing new dietary guidelines, which will be of great public health importance. However, more additional randomised controlled trials are warranted to clarify the causality.
The “Era of the City” as an Emerging Challenge to Liberal Constitutional Democracy
Authors: Hirschl Ran 
Published: December 2022

AbstractExtensive urbanization is one of the most significant demographic and geopolitical phenomena of our time. Yet, with few exceptions, constitutional theory has failed to turn its attention to this crucial trend. In particular, the burgeoning constitutional literature aimed at addressing phenomena such as democratic backsliding, constitutional retrogression, and populist threats to judicial independence and the rule of law has failed to respond to the significance of place as an emerging cleavage in contemporary politics. An alarming disconnect has emerged between constitutionalism's overwhelmingly statist (or Westphalian) outlook and the reality of geographically localized concentration of worldviews, policy preferences, and political identities. In this essay, I identify urban agglomeration and the accompanying resurgence of the urban-rural divide as posing a critical challenge to liberal constitutional democracy, and argue that the time is ripe to pay closer attention to the spatial dimension of constitutional governance and its impact on the rise of anti-establishment political resentment. To that end, in the essay's final part I identify several areas of constitutional law and theory that appear to hold some intellectual promise in thinking creatively about mitigating the urban-rural divide, and about the mounting urban challenge more generally.
KLAUS-Tr: Knowledge & learning-based unit focused arithmetic word problem solver for transfer cases
Authors: Kumar Suresh , Kumar P. Sreenivasa 
Published: December 2022

AbstractSolving the Arithmetic Word Problems (AWPs) using AI techniques has attracted much attention in recent years. We feel that the current AWP solvers are under-utilizing the relevant domain knowledge. We present a knowledge- and learning-based system that effectively solves AWPs of a specific type—those that involve transfer of objects from one agent to another (Transfer Cases (TC)). We represent the knowledge relevant to these problems as TC Ontology. The sentences in TC-AWPs contain information of essentially four types: before-transfer, transfer, after-transfer, and query. Our system (KLAUS-Tr) uses statistical classifier to recognize the types of sentences. The sentence types guide the information extraction process used to identify the agents, quantities, units, types of objects, and the direction of transfer from the AWP text. The extracted information is represented as an RDF graph that utilizes the TC Ontology terminology. To solve the given AWP, we utilize semantic web rule language (SWRL) rules that capture the knowledge about how object transfer affects the RDF graph of the AWP. Using the TC ontology, we also analyze if the given problem is consistent or otherwise. The different ways in which TC-AWPs can be inconsistent are encoded as SWRL rules. Thus, KLAUS-Tr can identify if the given AWP is invalid and accordingly notify the user. Since the existing datasets do not have inconsistent AWPs, we create AWPs of this type and augment the datasets. We have implemented KLAUS-Tr and tested it on TC-type AWPs drawn from the All-Arith and other datasets. We find that TC-AWPs constitute about 40% of the AWPs in a typical dataset like All-Arith. Our system achieves an impressive accuracy of 92%, thus improving the state-of-the-art significantly. We plan to extend the system to handle AWPs that contain multiple transfers of objects and also offer explanations of the solutions.
Understanding Internal Cluster Variability Through Subcluster Metric Analysis in a Geophysical Context
Authors: Schuddeboom A. J. , McDonald A. J. 
Published: December 2022

AbstractClustering algorithms are commonly used for inspecting the behavior of clouds in both model and satellite data sets. Often overlooked in cluster analysis is the variability that occurs within any clusters generated. This is particularly important in the geophysics where clusters are often generated with a focus on interpretability over mathematical optimization. Two metrics, the Davies‐Bouldin index and the subsom entropy, are used to identify clusters with large internal variability. These metrics are applied to an example set of clusters from prior research that were generated using cloud top pressure‐cloud optical thickness joint histograms from the Moderate Resolution Imaging Spectroradiometer data set. Applying these metrics to the clusters identifies one cluster in particular as a major outlier. Examining the calculations behind these metrics in more detail provides further information about the internal variability of the clusters. The clusters are also examined over several geographic regions showing mostly consistent behavior. There are, however, some large anomalies such as the behavior of the clear sky cluster or the behavior of several different clusters over the Arctic Ocean. To aide our interpretation of these results, two clusters are chosen for a detailed analysis of their subclusters. The geographic distributions and radiative properties of these subclusters are examined and clearly identify that subclusters have physically distinct behavior. This result illustrates that these metrics are capable of determining when a cluster contains physically distinct subclusters. This demonstrates the potential utility of these metrics if they were applied to other geophysical data sets.
Detailed 40Ar/39Ar Geochronology of the Loyalty and Three Kings Ridges Clarifies the Extent and Sequential Development of Eocene to Miocene Southwest Pacific Remnant Volcanic Arcs
Authors: Gans P. B. , Mortimer N. , Patriat M. , Turnbull R. E. , Crundwell M. P. , Agranier A. , Calvert A. T. , Seward G. , Etienne S. , Durance P. M. J. , Campbell H. J. , Collot J. 
Published: December 2022

AbstractThe 2015 VESPA voyage (Volcanic Evolution of South Pacific Arcs) was a seismic and rock dredging expedition to the Loyalty and Three Kings Ridges and South Fiji Basin. In this paper we present 33 40Ar/39Ar, 22 micropaleontological, and two U/Pb ages for igneous and sedimentary rocks from 33 dredge sites in this little‐studied part of the southwest Pacific Ocean. Igneous rocks include basalts, dolerites, basaltic andesites, trachyandesites, and a granite. Successful Ar/Ar dating of altered and/or low‐K basalts was achieved through careful sample selection and processing, detailed petrographic and element mapping of groundmass, and incremental heating experiments on both phenocryst and groundmass separates to interpret the complex spectra produced by samples having multiple K reservoirs. The 40Ar/39Ar ages of most of the sampled lavas, irrespective of composition, are latest Oligocene to earliest Miocene (25–22 Ma); two are Eocene (39–36 Ma). The granite has a U/Pb zircon age of 23.6 ± 0.3 Ma. 40Ar/39Ar lava ages are corroborated by microfossil ages from associated sedimentary rocks. The VESPA lavas are part of a >3,000 km long disrupted belt of Eocene to Miocene subduction‐related volcanic rocks. The belt includes arc rocks in Northland New Zealand, Northland Plateau, Three Kings Ridge, and Loyalty Ridge and, speculatively, D’Entrecasteaux Ridge. This belt is the product of superimposed Eocene and Oligocene‐Miocene remnant volcanic arcs that were stranded along and near the edge of Zealandia while still‐active arc belts migrated east with the Pacific trench.
Divergent roles of herbivory in eutrophying forests
Authors: Segar Josiane , Pereira Henrique M. , Baeten Lander , Bernhardt-Römermann Markus , De Frenne Pieter , Fernández Néstor , Gilliam Frank S. , Lenoir Jonathan , Ortmann-Ajkai Adrienne , Verheyen Kris , Waller Donald , Teleki Balázs , Brunet Jörg , Chudomelová Markéta , Decocq Guillaume , Dirnböck Thomas , Hédl Radim , Heinken Thilo , Jaroszewicz Bogdan , Kopecký Martin , Macek Martin , Máliš František , Naaf Tobias , Orczewska Anna , Reczynska Kamila , Schmidt Wolfgang , Šebesta Jan , Stachurska-Swakoń Alina , Standovár Tibor , Swierkosz Krzysztof , Vild Ondřej , Wulf Monika , Staude Ingmar R. 
Published: December 2022

AbstractUngulate populations are increasing across Europe with important implications for forest plant communities. Concurrently, atmospheric nitrogen (N) deposition continues to eutrophicate forests, threatening many rare, often more nutrient-efficient, plant species. These pressures may critically interact to shape biodiversity as in grassland and tundra systems, yet any potential interactions in forests remain poorly understood. Here, we combined vegetation resurveys from 52 sites across 13 European countries to test how changes in ungulate herbivory and eutrophication drive long-term changes in forest understorey communities. Increases in herbivory were associated with elevated temporal species turnover, however, identities of winner and loser species depended on N levels. Under low levels of N-deposition, herbivory favored threatened and small-ranged species while reducing the proportion of non-native and nutrient-demanding species. Yet all these trends were reversed under high levels of N-deposition. Herbivores also reduced shrub cover, likely exacerbating N effects by increasing light levels in the understorey. Eutrophication levels may therefore determine whether herbivory acts as a catalyst for the “N time bomb” or as a conservation tool in temperate forests.
Design of a self-driven probiotic-CRISPR/Cas9 nanosystem for sono-immunometabolic cancer therapy
Authors: Yu Jifeng , Zhou Bangguo , Zhang Shen , Yin Haohao , Sun Liping , Pu Yinying , Zhou Boyang , Sun Yikang , Li Xiaolong , Fang Yan , Wang Lifan , Zhao Chongke , Du Dou , Zhang Yan , Xu Huixiong 
Published: December 2022

AbstractReprogramming the tumor immunosuppressive microenvironment is a promising strategy for improving tumor immunotherapy efficacy. The clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated protein 9 system can be used to knockdown tumor immunosuppression-related genes. Therefore, here, a self-driven multifunctional delivery vector is constructed to efficiently deliver the CRISPR-Cas9 nanosystem for indoleamine 2,3-dioxygenase-1 (IDO1) knockdown in order to amplify immunogenic cell death (ICD) and then reverse tumor immunosuppression. Lactobacillus rhamnosus GG (LGG) is a self-driven safety probiotic that can penetrate the hypoxia tumor center, allowing efficient delivery of the CRISPR/Cas9 system to the tumor region. While LGG efficiently colonizes the tumor area, it also stimulates the organism to activate the immune system. The CRISPR/Cas9 nanosystem can generate abundant reactive oxygen species (ROS) under the ultrasound irradiation, resulting in ICD, while the produced ROS can induce endosomal/lysosomal rupture and then releasing Cas9/sgRNA to knock down the IDO1 gene to lift immunosuppression. The system generates immune responses that effectively attack tumor cells in mice, contributing to the inhibition of tumor re-challenge in vivo. In addition, this strategy provides an immunological memory effect which offers protection against lung metastasis.
Atomic design of dual-metal hetero-single-atoms for high-efficiency synthesis of natural flavones
Authors: Zhao Xin , Fang Ruiqi , Wang Fengliang , Kong Xiangpeng , Li Yingwei 
Published: December 2022

AbstractSingle-atom (SA) catalysts provide extensive possibilities in pursuing fantastic catalytic performances, while their preparation still suffers from metal aggregation and pore collapsing during pyrolysis. Here we report a versatile medium-induced infiltration deposition strategy for the fabrication of SAs and hetero-SAs (MaN4/MbN4@NC; Ma = Cu, Co, Ni, Mn, Mb = Co, Cu, Fe, NC = N-doped carbon). In-situ and control experiments reveal that the catalyst fabrication relies on the “step-by-step” evolution of Ma-containing metal-organic framework (MOF) template and Mb-based metal precursor, during which molten salt acts as both pore generator in the MOF transformation, and carrier for the oriented infiltration and deposition of the latter to eventually yield metal SAs embedded on hierarchically porous support. The as-prepared hetero-SAs show excellent catalytic performances in the general synthesis of 33 kinds of natural flavones. The highly efficient synthesis is further strengthened by the reliable durability of the catalyst loaded in a flow reactor. Systematic characterizations and mechanism studies suggest that the superior catalytic performances of CuN4/CoN4@NC are attributed to the facilitated O2activating-splitting process and significantly reduced reaction energy barriers over CoN4due to the synergetic interactions of the adjacent CuN4.
Actin-microtubule cytoskeletal interplay mediated by MRTF-A/SRF signaling promotes dilated cardiomyopathy caused by LMNA mutations
Authors: Le Dour Caroline , Chatzifrangkeskou Maria , Macquart Coline , Magiera Maria M. , Peccate Cécile , Jouve Charlène , Virtanen Laura , Heliö Tiina , Aalto-Setälä Katriina , Crasto Silvia , Cadot Bruno , Cardoso Déborah , Mougenot Nathalie , Adesse Daniel , Di Pasquale Elisa , Hulot Jean-Sébastien , Taimen Pekka , Janke Carsten , Muchir Antoine 
Published: December 2022

AbstractMutations in the lamin A/C gene (LMNA) cause dilated cardiomyopathy associated with increased activity of ERK1/2 in the heart. We recently showed that ERK1/2 phosphorylates cofilin-1 on threonine 25 (phospho(T25)-cofilin-1) that in turn disassembles the actin cytoskeleton. Here, we show that in muscle cells carrying a cardiomyopathy-causingLMNAmutation, phospho(T25)-cofilin-1 binds to myocardin-related transcription factor A (MRTF-A) in the cytoplasm, thus preventing the stimulation of serum response factor (SRF) in the nucleus. Inhibiting the MRTF-A/SRF axis leads to decreased α-tubulin acetylation by reducing the expression ofATAT1gene encoding α-tubulin acetyltransferase 1. Hence, tubulin acetylation is decreased in cardiomyocytes derived from male patients withLMNAmutations and in heart and isolated cardiomyocytes fromLmnap.H222P/H222Pmale mice. InAtat1knockout mice, deficient for acetylated α-tubulin, we observe left ventricular dilation and mislocalization of Connexin 43 (Cx43) in heart. Increasing α-tubulin acetylation levels inLmnap.H222P/H222Pmice with tubastatin A treatment restores the proper localization of Cx43 and improves cardiac function. In summary, we show for the first time an actin-microtubule cytoskeletal interplay mediated by cofilin-1 and MRTF-A/SRF, promoting the dilated cardiomyopathy caused byLMNAmutations. Our findings suggest that modulating α-tubulin acetylation levels is a feasible strategy for improving cardiac function.
Safeguarding genome integrity during gene-editing therapy in a mouse model of age-related macular degeneration
Authors: Yin Jianhang , Fang Kailun , Gao Yanxia , Ou Liqiong , Yuan Shaopeng , Xin Changchang , Wu Weiwei , Wu Wei-wei , Hong Jiaxu , Yang Hui , Hu Jiazhi 
Published: December 2022

AbstractEnsuring genome safety during gene editing is crucial for clinical translation of the high-efficient CRISPR-Cas9 toolbox. Therefore, the undesired events including chromosomal translocations, vector integrations, and large deletions arising during therapeutic gene editing remain to be adequately addressed or tackled in vivo. Here, we apply CRISPR-Cas9TX in comparison to CRISPR-Cas9 to target Vegfa for the treatment of age-related macular degeneration (AMD) disease in a mouse model. AAV delivery of both CRISPR-Cas9 and CRISPR-Cas9TX can efficiently inhibit laser-induced neovascularization. Importantly, Cas9TX almost eliminates chromosomal translocations that occur at a frequency of approximately 1% in Cas9-edited mouse retinal cells. Strikingly, the widely observed AAV integration at the target Vegfa site is also greatly reduced from nearly 50% of edited events to the background level during Cas9TX editing. Our findings reveal that chromosomal structural variations routinely occur during in vivo genome editing and highlight Cas9TX as a superior form of Cas9 for in vivo gene disruption.
Genetically programmed cell-based synthesis of non-natural peptide and depsipeptide macrocycles
Authors: Spinck Martin , Piedrafita Carlos , Robertson Wesley E. , Elliott Thomas S. , Cervettini Daniele , de la Torre Daniel , Chin Jason W. 
Published: December 2022

AbstractThe direct genetically encoded cell-based synthesis of non-natural peptide and depsipeptide macrocycles is an outstanding challenge. Here we programme the encoded synthesis of 25 diverse non-natural macrocyclic peptides, each containing two non-canonical amino acids, in Syn61Δ3-derived cells; these cells contain a synthetic Escherichia coli genome in which the annotated occurrences of two sense codons and a stop codon, and the cognate transfer RNAs (tRNAs) and release factor that normally decode these codons, have been removed. We further demonstrate that pyrrolysyl-tRNA synthetase/tRNA pairs from distinct classes can be engineered to direct the co-translational incorporation of diverse alpha hydroxy acids, with both aliphatic and aromatic side chains. We define 49 engineered mutually orthogonal pairs that recognize distinct non-canonical amino acids or alpha hydroxy acids and decode distinct codons. Finally, we combine our advances to programme Syn61Δ3-derived cells for the encoded synthesis of 12 diverse non-natural depsipeptide macrocycles, which contain two non-canonical side chains and either one or two ester bonds.
Experimental observation of Berry phases in optical Möbius-strip microcavities
Authors: Wang Jiawei , Valligatla Sreeramulu , Yin Yin , Schwarz Lukas , Medina-Sánchez Mariana , Baunack Stefan , Lee Ching Hua , Thomale Ronny , Li Shilong , Fomin Vladimir M. , Ma Libo , Schmidt Oliver G. 
Published: December 2022

AbstractThe Möbius strip, a fascinating loop structure with one-sided topology, provides a rich playground for manipulating the non-trivial topological behaviour of spinning particles, such as electrons, polaritons and photons, in both real and parameter spaces. For photons resonating in a Möbius-strip cavity, the occurrence of an extra phase—known as the Berry phase—with purely topological origin is expected due to its non-trivial evolution in parameter space. However, despite numerous theoretical investigations, characterizing the optical Berry phase in a Möbius-strip cavity has remained elusive. Here we report the experimental observation of the Berry phase generated in optical Möbius-strip microcavities. In contrast to theoretical predictions in optical, electronic and magnetic Möbius-topology systems where only Berry phase π occurs, we demonstrate that a variable Berry phase smaller than π can be acquired by generating elliptical polarization of resonating light. Möbius-strip microcavities as integrable and Berry-phase-programmable optical systems are of great interest in topological physics and emerging classical or quantum photonic applications.
Multiplexed transcriptome discovery of RNA-binding protein binding sites by antibody-barcode eCLIP
Authors: Lorenz Daniel A. , Her Hsuan-Lin , Shen Kylie A. , Rothamel Katie , Hutt Kasey R. , Nojadera Allan C. , Bruns Stephanie C. , Manakov Sergei A. , Yee Brian A. , Chapman Karen B. , Yeo Gene W. 
Published: December 2022

AbstractUltraviolet crosslinking and immunoprecipitation (CLIP) methodologies enable the identification of RNA binding sites of RNA-binding proteins (RBPs). Despite improvements in the library preparation of RNA fragments, the enhanced CLIP (eCLIP) protocol requires 4 days of hands-on time and lacks the ability to process several RBPs in parallel. We present a new method termed antibody-barcode eCLIP that utilizes DNA-barcoded antibodies and proximity ligation of the DNA oligonucleotides to RBP-protected RNA fragments to interrogate several RBPs simultaneously. We observe performance comparable with that of eCLIP with the advantage of dramatically increased scaling while maintaining the same material requirement of a single eCLIP experiment.
Diverse silent chromatin states modulate genome compartmentalization and loop extrusion barriers
Authors: Spracklin George , Abdennur Nezar , Imakaev Maxim , Chowdhury Neil , Pradhan Sriharsa , Mirny Leonid A. , Dekker Job 
Published: December 2022

AbstractThe relationships between chromosomal compartmentalization, chromatin state and function are poorly understood. Here by profiling long-range contact frequencies in HCT116 colon cancer cells, we distinguish three silent chromatin states, comprising two types of heterochromatin and a state enriched for H3K9me2 and H2A.Z that exhibits neutral three-dimensional interaction preferences and which, to our knowledge, has not previously been characterized. We find that heterochromatin marked by H3K9me3, HP1α and HP1β correlates with strong compartmentalization. We demonstrate that disruption of DNA methyltransferase activity greatly remodels genome compartmentalization whereby domains lose H3K9me3-HP1α/β binding and acquire the neutrally interacting state while retaining late replication timing. Furthermore, we show that H3K9me3-HP1α/β heterochromatin is permissive to loop extrusion by cohesin but refractory to CTCF binding. Together, our work reveals a dynamic structural and organizational diversity of the silent portion of the genome and establishes connections between the regulation of chromatin state and chromosome organization, including an interplay between DNA methylation, compartmentalization and loop extrusion.