bluuebunny/crossref_metadata_2025_split huggingface dataset:
Obsessive–compulsive disorder and the associated risk of autoimmune skin diseases: a nationwide population-based cohort study
Authors: Chou Yu-Ju , Tai Ying-Hsuan , Dai Ying-Xiu , Lee Din-Dar , Chang Yun-Ting , Chen Tzeng-Ji , Chen Mu-Hong 
Published: February 2022

AbstractBackgroundThe concurrent incidence of autoimmune comorbidities in obsessive–compulsive disorder (OCD) is known. However, the association between OCD and related autoimmune skin diseases (ASDs) has not been well studied.ObjectiveThis study aimed to investigate the association between OCD and the risk of ASDs.MethodsTo assess the risk of developing ASDs, we recruited 44 324 patients with OCD and 177 296 matched controls from the National Health Insurance Research Database in Taiwan. A Cox regression model was used for the analyses.ResultsAfter adjusting for confounders, an increased risk of ASDs among the patients with OCD (adjusted hazard ratio [aHR]: 6.36; 95% confidence interval [CI]: 5.43-7.45) was found when compared to the controls. Statistically significant associations were found between OCD and seven individual ASDs, including psoriasis (aHR: 12.52; 95% CI: 8.78-17.85), lichen planus (aHR: 27.22; 95% CI: 13.09-56.60), alopecia areata (aHR: 13.69; 95% CI: 9.38-19.98), autoimmune bullous diseases (aHR: 4.30; 95% CI: 2.03-9.11), hidradenitis suppurativa (aHR: 29.95; 95% CI: 3.35-267.62), vitiligo (aHR: 9.35; 95% CI: 5.35-16.32), and lupus erythematosus (aHR: 2.10; 95% CI: 1.52-2.91).ConclusionsPatients with OCD had an increased risk of developing ASDs compared to matched controls. Further studies are required to clarify the underlying mechanisms.
Symbolic Specialization of Rewriting Logic Theories withPresto
Authors: ALPUENTE MARÍA , ESCOBAR SANTIAGO , SAPIÑA JULIA , BALLIS DEMIS 
Published: February 2022

AbstractThis paper introduces$\tt{{Presto}}$, a symbolic partial evaluator for Maude’s rewriting logic theories that can improve system analysis and verification. In$\tt{{Presto}}$, the automated optimization of a conditional rewrite theory$\mathcal{R}$(whose rules define the concurrent transitions of a system) is achieved by partially evaluating, with respect to the rules of$\mathcal{R}$, an underlying, companion equational logic theory$\mathcal{E}$that specifies the algebraic structure of the system states of$\mathcal{R}$. This can be particularly useful for specializing an overly general equational theory$\mathcal{E}$whose operators may obey complex combinations of associativity, commutativity, and/or identity axioms, when being plugged into a host rewrite theory$\mathcal{R}$as happens, for instance, in protocol analysis, where sophisticated equational theories for cryptography are used.$\tt{{Presto}}$implements different unfolding operators that are based onfolding variant narrowing(the symbolic engine of Maude’s equational theories). When combined with an appropriate abstraction algorithm, they allow the specialization to be adapted to the theory termination behavior and bring significant improvement while ensuring strong correctness and termination of the specialization. We demonstrate the effectiveness of$\tt{{Presto}}$in several examples of protocol analysis where it achieves a significant speed-up. Actually, the transformation provided by$\tt{{Presto}}$may cut down an infinite folding variant narrowing space to a finite one, and moreover, some of the costly algebraic axioms and rule conditions may be eliminated as well. As far as we know, this is the first partial evaluator for Maude that respects the semantics of functional, logic, concurrent, and object-oriented computations.
The Role of Internal Variability in ITCZ Changes Over the Last Millennium
Authors: Roldán‐Gómez P. J. , González‐Rouco J. F. , Melo‐Aguilar C. , Smerdon J. E. 
Published: February 2022

AbstractTropical hydroclimate is modulated by the position and intensity of the Intertropical Convergence Zone (ITCZ). Reconstructions and simulations of the Last Millennium (LM) suggest latitudinal variations of the ITCZ that impact the hydroclimate over large regions of the world. These ITCZ shifts have been generally linked to external radiative forcing, but analyses of the Community Earth System Model – Last Millennium Ensemble (CESM‐LME) demonstrate a significant contribution of internal variability over multidecadal and centennial timescales. In contrast to changes driven by external forcing, which are associated with an asymmetric warming between the Northern and Southern Hemispheres, the contribution of internal variability in the CESM‐LME is associated with cooling and warming of the eastern Pacific. While external forcing remains the main driver of ITCZ changes in the Atlantic basin, the contribution of internal variability in the CESM‐LME exceeds that of the forcing for the Pacific and Indian Ocean basins.
Multidecadal Trends in Organic Carbon Flux Through a Grassland River Network Shaped by Human Controls and Climatic Cycles
Authors: Johnston Sarah Ellen , Gunawardana Panditha V. S. L. , Rood Stewart B. , Bogard Matthew J. 
Published: February 2022

AbstractGrasslands are among the most disturbed systems on Earth due to extensive agricultural development and river regulation. To define how these factors impact the movement of carbon (C) through river networks, we quantified multi‐decadal, seasonal patterns of dissolved organic C (DOC) fluxes through a grassland river network. Despite urbanization and effluent release in recent decades, we did not observe trends in DOC fluxes over 20 to 40 year monthly sample records. High interannual variability in DOC flux was linked to climate teleconnections, most strongly the Pacific Decadal Oscillation. Human impacts were more apparent on the seasonality of flux, since spring export dominated DOC flux in most sub‐watersheds, but seasonal changes were absent at the river mouth due to downstream flow control. In grassland regions, human impacts on DOC flux are complex, and subtle long‐term changes may be difficult to identify in contemporary monitoring records due to increasing hydro‐climatic variability.
Daytime F Region Echoes at Equatorial Ionization Anomaly Crest During Geomagnetic Quiet Period: Observations From Multi‐Instruments
Authors: Liu Yi , Deng Zhongxin , Xu Tong , Kong Jian , Zhou Chen , Yao Yibin , Tang Qiong , Zhao Zhengyu 
Published: February 2022

AbstractBy using Qujing very high frequency radar (25.6°N, 103.7°E, magnetic latitude 16.1°N, magnetic longitude 177.0°E), daytime F region echoes were reported at equatorial ionization anomaly crest on 26 June 2020. Radar interferometry experiment was performed during the observation period. The observed results show that the spatial distributions of daytime F region echo pattern were about 150 km, 200 km, and 180 km in the zonal, meridional, and height extents, respectively. In addition, we observed a remarkable eastward drift of F region echoes with a mean velocity of about 50 m/s. To investigate the possible generation mechanism of daytime F region echoes, simultaneous occurrences of ionospheric disturbance and atmospheric gravity wave activities were presented by combining with the observations of ionosonde, global position system stations and FY‐4A satellite. The existence of gravity wave from the deep convective activities in the lower atmosphere was confirmed by using FY‐4A satellite measurements. The gravity wave signatures were also observed in the time series of virtual height deviations of sporadic E (dhES) and total electron content near the region where the F region echoes. We surmise that ionospheric disturbance in the F region could be excited during atmospheric gravity wave activities. Then the large‐scale ionospheric disturbance could further evolve into small‐scale irregularity producing radar echoes through the non‐linear cascade process.
Dynamic Contributions of Stratified Groundwater to Streams Controls Seasonal Variations of Streamwater Transit Times
Authors: Marçais Jean , Derry Louis A. , Guillaumot Luca , Aquilina Luc , de Dreuzy Jean‐Raynald 
Published: February 2022

AbstractStreamwater transit time distributions display a variable proportion of old waters (≥1 year). We hypothesize that the corresponding long transit times result from groundwater contributions to the stream and that seasonal streamwater transit time variations result from (a) the variable contributions of different flowpaths (overland flow, seepage flow and baseflow) and (b) the stratification of groundwater residence times. We develop a parsimonious model to capture the groundwater contribution to the stream discharge and its effect on transient transit times. Infiltration is partitioned according to the aquifer saturation between Boussinesq groundwater flow and overland flow. Time‐variable transit time distributions are obtained with a new 2D particle tracking algorithm. Hydraulic conductivity, total and drainable porosities are calibrated by using discharge and CFC tracer data on a crystalline catchment located in Brittany (France). The calibrated models succeed in reproducing CFCs concentrations and discharge dynamics. The groundwater flow contribution to the stream is controlled by the aquifer hydraulic conductivity, while its age is controlled by the drainable and total porosities. Old groundwater (≥1 year) is the source for approximately 75% of the streamflow with strong seasonal variations (between 40% and 95%). Mean transit times are approximately 13 years, varying between 6 and 20 years, proportional to the groundwater contribution. These seasonal variations are driven by the groundwater versus overland flow partitioning. The stratification of groundwater residence times in the aquifer plays a minor role in the streamwater transit times but is key for the transit time dynamics of the groundwater contribution to the stream.
Organizational Principles of Hyporheic Exchange Flow and Biogeochemical Cycling in River Networks Across Scales
Authors: Krause Stefan , Abbott Benjamin W. , Baranov Viktor , Bernal Susana , Blaen Phillip , Datry Thibault , Drummond Jennifer , Fleckenstein Jan H. , Velez Jesus Gomez , Hannah David M. , Knapp Julia L. A. , Kurz Marie , Lewandowski Jörg , Martí Eugènia , Mendoza‐Lera Clara , Milner Alexander , Packman Aaron , Pinay Gilles , Ward Adam S. , Zarnetzke Jay P. 
Published: February 2022

AbstractHyporheic zones increase freshwater ecosystem resilience to hydrological extremes and global environmental change. However, current conceptualizations of hyporheic exchange, residence time distributions, and the associated biogeochemical cycling in streambed sediments do not always accurately explain the hydrological and biogeochemical complexity observed in streams and rivers. Specifically, existing conceptual models insufficiently represent the coupled transport and reactivity along groundwater and surface water flow paths, the role of autochthonous organic matter in streambed biogeochemical functioning, and the feedbacks between surface‐subsurface ecological processes, both within and across spatial and temporal scales. While simplified approaches to these issues are justifiable and necessary for transferability, the exclusion of important hyporheic processes from our conceptualizations can lead to erroneous conclusions and inadequate understanding and management of interconnected surface water and groundwater environments. This is particularly true at the landscape scale, where the organizational principles of spatio‐temporal dynamics of hyporheic exchange flow (HEF) and biogeochemical processes remain largely uncharacterized. This article seeks to identify the most important drivers and controls of HEF and biogeochemical cycling based on a comprehensive synthesis of findings from a wide range of river systems. We use these observations to test current paradigms and conceptual models, discussing the interactions of local‐to‐regional hydrological, geomorphological, and ecological controls of hyporheic zone functioning. This improved conceptualization of the landscape organizational principles of drivers of HEF and biogeochemical processes from reach to catchment scales will inform future river research directions and watershed management strategies.
Ionizable liposomal siRNA therapeutics enables potent and persistent treatment of Hepatitis B
Authors: Huang Yuanyu , Zheng Shuquan , Guo Zhaoxu , de Mollerat du Jeu Xavier , Liang Xing-Jie , Yang Zhiwei , Zhang Hong-Yan , Gao Shan , Liang Zicai 
Published: February 2022

AbstractSmall interfering RNA (siRNA) constitutes a promising therapeutic modality supporting the potential functional cure of hepatitis B. A novel ionizable lipidoid nanoparticle (RBP131) and a state-of-the-art lyophilization technology were developed in this study, enabling to deliver siRNA targeting apolipoprotein B (APOB) into the hepatocytes with an ED50 of 0.05 mg/kg after intravenous injection. In addition, according to the requirements of Investigational New Drug (IND) application, a potent siRNA targeting hepatitis B virus (HBV) was selected and encapsulated with RBP131 to fabricate a therapeutic formulation termed RB-HBV008. Efficacy investigations in transient and transgenic mouse models revealed that the expressions of viral RNAs and antigens (HBsAg and HBeAg), as well as viral DNA, were repressed, dose-dependently and time-dependently at multilog decreasing amplitude, in both circulation and liver tissue. In contrast, entecavir (ETV), the first-line clinically-employed nucleoside analog drug, barely recused the antigen expression, although it triggered as high as 3.50 log reduction of viral DNA, in line with clinical observations. Moreover, the toxicity profiles suggested satisfactory safety outcomes with ten times the therapeutic window. Therefore, this study provides an effective nucleic acid delivery system and a promising RNAi agent for the treatment of hepatitis B.
YAP ISGylation increases its stability and promotes its positive regulation on PPP by stimulating 6PGL transcription
Authors: Xue Xiangfei , Tian Xiaoting , Zhang Congcong , Miao Yayou , Wang Yikun , Peng Yingxiu , Qiu Shiyu , Wang Hong , Cui Jiangtao , Cao Leiqun , Sun Fenyong , Qiao Yongxia , Zhang Xiao 
Published: February 2022

AbstractYes-associated protein (YAP) activation is crucial for tumor formation and development, and its stability is regulated by ubiquitination. ISGylation is a type of ubiquitination like post-translational modification, whereas whether YAP is ISGylated and how ISGylation influences YAP ubiquitination-related function remains uncovered. In addition, YAP can activate glucose metabolism by activating the hexosamine biosynthesis pathway (HBP) and glycolysis, and generate a large number of intermediates to promote tumor proliferation. However, whether YAP stimulates the pentose phosphate pathway (PPP), another tumor-promoting glucose metabolism pathway, and the relationship between this stimulation and ISGylation needs further investigation. Here, we found that YAP was ISGylated and this ISGylation inhibited YAP ubiquitination, proteasome degradation, interaction with-beta-transducin repeat containing E3 ubiquitin-protein ligase (βTrCP) to promote YAP stability. However, ISGylation-induced pro-YAP effects were abolished by YAP K497R (K, lysine; R, arginine) mutation, suggesting K497 could be the major YAP ISGylation site. In addition, YAP ISGylation promoted cell viability, cell-derived xenograft (CDX) and patient-derived xenograft (PDX) tumor formation. YAP ISGylation also increased downstream genes transcription, including one of the key enzymes of PPP, 6-phosphogluconolactonase (6PGL). Mechanistically, YAP promoted 6PGL transcription by simultaneously recruiting SMAD family member 2 (SMAD2) and TEA domain transcription factor 4 (TEAD4) binding to the 6PGL promoter to activate PPP. In clinical lung adenocarcinoma (LUAD) specimens, we found that YAP ISGylation degree was positively associated with 6PGL mRNA level, especially in high glucose LUAD tissues compared to low glucose LUAD tissues. Collectively, this study suggested that YAP ISGylation is critical for maintaining its stability and further activation of PPP. Targeting ISGylated YAP might be a new choice for hyperglycemia cancer treatment.
Protein nanowires with tunable functionality and programmable self-assembly using sequence-controlled synthesis
Authors: Shapiro Daniel Mark , Mandava Gunasheil , Yalcin Sibel Ebru , Arranz-Gibert Pol , Dahl Peter J. , Shipps Catharine , Gu Yangqi , Srikanth Vishok , Salazar-Morales Aldo I. , O’Brien J. Patrick , Vanderschuren Koen , Vu Dennis , Batista Victor S. , Malvankar Nikhil S. , Isaacs Farren J. 
Published: February 2022

AbstractAdvances in synthetic biology permit the genetic encoding of synthetic chemistries at monomeric precision, enabling the synthesis of programmable proteins with tunable properties. Bacterial pili serve as an attractive biomaterial for the development of engineered protein materials due to their ability to self-assemble into mechanically robust filaments. However, most biomaterials lack electronic functionality and atomic structures of putative conductive proteins are not known. Here, we engineer high electronic conductivity in pili produced by a genomically-recoded E. coli strain. Incorporation of tryptophan into pili increased conductivity of individual filaments >80-fold. Computationally-guided ordering of the pili into nanostructures increased conductivity 5-fold compared to unordered pili networks. Site-specific conjugation of pili with gold nanoparticles, facilitated by incorporating the nonstandard amino acid propargyloxy-phenylalanine, increased filament conductivity ~170-fold. This work demonstrates the sequence-defined production of highly-conductive protein nanowires and hybrid organic-inorganic biomaterials with genetically-programmable electronic functionalities not accessible in nature or through chemical-based synthesis.
Coordinated hippocampal-thalamic-cortical communication crucial for engram dynamics underneath systems consolidation
Authors: Tomé Douglas Feitosa , Sadeh Sadra , Clopath Claudia 
Published: February 2022

AbstractSystems consolidation refers to the time-dependent reorganization of memory representations or engrams across brain regions. Despite recent advancements in unravelling this process, the exact mechanisms behind engram dynamics and the role of associated pathways remain largely unknown. Here we propose a biologically-plausible computational model to address this knowledge gap. By coordinating synaptic plasticity timescales and incorporating a hippocampus-thalamus-cortex circuit, our model is able to couple engram reactivations across these regions and thereby reproduce key dynamics of cortical and hippocampal engram cells along with their interdependencies. Decoupling hippocampal-thalamic-cortical activity disrupts systems consolidation. Critically, our model yields testable predictions regarding hippocampal and thalamic engram cells, inhibitory engrams, thalamic inhibitory input, and the effect of thalamocortical synaptic coupling on retrograde amnesia induced by hippocampal lesions. Overall, our results suggest that systems consolidation emerges from coupled reactivations of engram cells in distributed brain regions enabled by coordinated synaptic plasticity timescales in multisynaptic subcortical-cortical circuits.
Single-cell tumor-immune microenvironment of BRCA1/2 mutated high-grade serous ovarian cancer
Authors: Launonen I.-M. , Lyytikäinen N. , Casado J. , Anttila E. A. , Szabó A. , Haltia U.-M. , Jacobson C. A. , Lin J. R. , Maliga Z. , Howitt B. E. , Strickland K. C. , Santagata S. , Elias K. , D’Andrea A. D. , Konstantinopoulos P. A. , Sorger P. K. , Färkkilä A. 
Published: February 2022

AbstractThe majority of high-grade serous ovarian cancers (HGSCs) are deficient in homologous recombination (HR) DNA repair, most commonly due to mutations or hypermethylation of the BRCA1/2 genes. We aimed to discover how BRCA1/2 mutations shape the cellular phenotypes and spatial interactions of the tumor microenvironment. Using a highly multiplex immunofluorescence and image analysis we generate spatial proteomic data for 21 markers in 124,623 single cells from 112 tumor cores originating from 31 tumors with BRCA1/2 mutation (BRCA1/2mut), and from 13 tumors without alterations in HR genes. We identify a phenotypically distinct tumor microenvironment in the BRCA1/2mut tumors with evidence of increased immunosurveillance. Importantly, we report a prognostic role of a proliferative tumor-cell subpopulation, which associates with enhanced spatial tumor-immune interactions by CD8+ and CD4 + T-cells in the BRCA1/2mut tumors. The single-cell spatial landscapes indicate distinct patterns of spatial immunosurveillance with the potential to improve immunotherapeutic strategies and patient stratification in HGSC.
Dissolution and precipitation behaviors of zircon under the atmospheric environment
Authors: Kitagaki Toru , Yoshida Kenta , Liu Pengfei , Shobu Takahisa 
Published: February 2022

AbstractThe reactive behavior of zircon in three different solutions: 0.1 M HCl (aq), ultrapure water, and 0.1 M NaOH (aq) was examined under normal temperature and pressure conditions. Dissolved Si and Zr concentrations show that considerable Zr precipitated on the surface in all immersion cases. Bulk changes in the zircon were insignificant. However, the obvious surface change of the zircon immersed in 0.1 M NaOH (aq) was confirmed. Porous layer comprising an amorphous SiOx phase and needle crystals of ZrSiO4 around pores were detected on the near-surface area of the zircon immersed in 0.1 M NaOH (aq). Consequently, the reaction was limited when zircon was immersed in ultrapure water. Zr precipitated on the surface after the dissolution of ZrSiO4 in 0.1 M HCl (aq). Dissolved Zr and Si in 0.1 M NaOH (aq) precipitated on the surface, then the dissolution of ZrSiO4 formed a porous layer, and most dissolved Zr precipitated as zircon crystals.
Tuneable electron–magnon coupling of ferromagnetic surface states in PdCoO2
Authors: Mazzola F. , Yim C. -M. , Sunko V. , Khim S. , Kushwaha P. , Clark O. J. , Bawden L. , Marković I. , Chakraborti D. , Kim T. K. , Hoesch M. , Mackenzie A. P. , Wahl P. , King P. D. C. 
Published: February 2022

AbstractControlling spin wave excitations in magnetic materials underpins the burgeoning field of magnonics. Yet, little is known about how magnons interact with the conduction electrons of itinerant magnets, or how this interplay can be controlled. Via a surface-sensitive spectroscopic approach, we demonstrate a strong electron–magnon coupling at the Pd-terminated surface of the delafossite oxide PdCoO2, where a polar surface charge mediates a Stoner transition to itinerant surface ferromagnetism. We show how the coupling is enhanced sevenfold with increasing surface disorder, and concomitant charge carrier doping, becoming sufficiently strong to drive the system into a polaronic regime, accompanied by a significant quasiparticle mass enhancement. Our study thus sheds light on electron–magnon interactions in solid-state materials, and the ways in which these can be controlled.