bluuebunny/crossref_metadata_2025 huggingface dataset:
Formation and Persistence of Extensional Internally Drained Basins: The Case of the Fucino Basin (Central Apennines, Italy)
Authors: Lanari R. , Faccenna C. , Benedetti L. , Sembroni A. , Bellier O. , Menichelli I. , Primerano P. , Molin P.
Published: June 2021

The interaction between sedimentation/erosion and faulting represents one of the most intriguing topics in landscape and tectonics evolution. Only few studies have been able to document the feedback between faulting and sedimentary loading from field observations. Here, we focus on how sediment loading/unloading influences the dynamics of fault systems in the Fucino basin, in the Central Apennines (Italy). The Fucino basin represents a remarkable case study with respect to the other main extensional basins in the Apennines because of its large dimension, square shape, significant sediment thickness, and its endorheic nature throughout its evolution.

We present a detailed structural and geomorphologic analysis of the Fucino basin and its surroundings, investigating the kinematic and geometry of each main fault strand. The slickenlines analysis reveals multiple families of slip‐vectors and timing of activity, suggesting a change in extension slip‐direction from N240° to N200° during middle Pleistocene. Using a local isostatic model, we estimate that up to the 30% of the vertical geological displacement of the faults, which overall ranges from 0.5 to 2.5 km, is related to the sediment loading/unloading. We demonstrate a positive feedback between sedimentation and faulting which may also lead to a reorganization in fault kinematics related to a significant increase in vertical stress. We propose a conceptual model for the permanent endorheic configuration of the Fucino basin, which includes the effect of sediment loading.
The Evolution of Central Volcanoes in Ultraslow Rift Systems: Constraints From D. João de Castro Seamount, Azores
Authors: Romer R. H. W. , Beier C. , Haase K. M. , Eberts A. , Hübscher C.
Published: June 2021

The Dom João de Castro seamount in the Hirondelle Basin (Azores) is a central volcano on the ultraslow diverging Terceira Rift axis. The combination of structural and geochemical data provides insights into the evolution of central volcanoes in oceanic rift systems above the Azores melting anomaly. The orientation of fault scarps and volcanic structures at D. João de Castro and the adjacent Castro fissure zone indicate that the regional SW‐NE extending stress field dominates the morphology of the NW Hirondelle Basin. The regional tectonic stress field controls the crustal melt pathways and leads to dike emplacement along fissure zones and the prevalent eruption of mafic lavas. The occurrence of mafic to felsic lavas at D. João de Castro gives evidence for both a deep and a shallow crustal melt reservoir generating a subordinate local stress field at the seamount. New Sr‐Nd‐Pb isotope data along with incompatible trace element ratios indicate that D. João de Castro and the Castro Ridges originated from similarly heterogeneous mantle source but did not form simultaneously. Our new model implies that central volcanoes along the Terceira Rift form by the growth of volcanic ridges and transitioned into circular edifices after magmatic systems generate local changes in the regional lithospheric stress field. The geometry of D. João de Castro and other magmatic systems along the Terceira Rift combined with the alkaline nature of the erupted lavas, and the large lithosphere thickness indicates that young oceanic rifts are more similar to continental rifts rather than mid‐ocean ridges.
Early Oligocene Surface Uplift in Southwestern Montana During the North American Cordilleran Extension
Authors: Li Lin , Fan Majie , Zhu Lu
Published: June 2021

The topographic history of the North American Cordillera holds the key to understanding the tectonic and geodynamic processes of orogenesis and post‐orogenic collapse. In southwestern Montana and its adjacent regions, previous studies have suggested that the early middle Eocene rollback of the Farallon flat‐slab caused the latest topographic growth, after which regional mean elevations were progressively lowered due to extensional collapse. In this study, we report 60 new Eocene‐Miocene stable hydrogen isotopic values (δD) of hydrated volcanic glass from southwestern Montana to examine regional topographic history during the extension. The δD values show a two‐stage negative shift of ∼35‰ during the late Paleogene, the timing of which is further refined by published ages and new zircon U‐Pb ages. About 19‰ of the negative shift occurred during the late Eocene‐earliest Oligocene (∼40–32 Ma) when global and regional climate experienced cooling, and the shift can be mostly accounted for by climate change. The remaining 16‰ negative shift occurred during the early Oligocene (∼32–30 Ma), which can be best explained by regional surface uplift of 0.9 ± 0.5 km. This inferred surface uplift occurred more than 17 Myr after the initiation of the Cordilleran extension in this region, and thus challenges the traditional assumption of progressive topographic lowering during the post‐orogenic collapse. This surface uplift, if occurred, may reflect lower mantle lithosphere removal in southwestern Montana.
Book Publishing in the Space Sciences
Authors: Keiling Andreas , Gallardo-Lacourt Bea , Jia Xianzhe , Nakariakov Valery
Published: June 2021

An analysis of books in the space science disciplines: AGU’s portfolio, how we compare with other publishers, and how we could grow.
Impacts of Engineered Diversions and Natural Avulsions on Delta‐Lobe Stability
Authors: Carlson Brandee N. , Nittrouer Jeffrey A. , Swanson Travis E. , Moodie Andrew J. , Dong Tian Y. , Ma Hongbo , Kineke Gail C. , Pan Minglong , Wang Yuanjiang
Published: June 2021

Reduced sediment supply and rising sea levels are driving land submergence on deltas worldwide, motivating engineering practices that divert water and sediment to sustain coastal landforms. However, lobe response following channel abandonment by diversions has not been constrained by field‐scale studies. Herein, avulsion and engineered diversion scenarios are explored for the Huanghe delta (China), where three lobes were abandoned in the last 40 yr. Two lobes were completely cut off by diversions, and one naturally by an avulsion. Shoreline retreat rates are strikingly different: ∼400 m/yr for diverted lobes and ∼90 m/yr for avulsed lobe. We hypothesize that this variability is linked to vegetal cover across lobes, and therefore the capacity to buffer hydrodynamic reworking of shoreface sediment. Furthermore, the vegetal cover is related to lobe salinity and elevation, which vary by abandonment style. We offer this as a case study to inform about the efficacy of future delta diversions.
Liquidus Phase Relations and Solid‐Liquid Partitioning in the Fe‐Si‐C System Under Core Pressures
Authors: Hasegawa Masahiro , Hirose Kei , Oka Kenta , Ohishi Yasuo
Published: June 2021

Both silicon and carbon have been proposed to be important light elements in the Earth's core, in particular in the inner core. Here we performed melting experiments on the Fe‐Si‐C ternary system at ∼50, ∼136, and ∼200 GPa and determined the liquidus phase relations and the solid/liquid partition coefficients (D) of C and Si. The liquidus field of Fe shrinks at higher pressures, which narrows down the possible outer core liquid composition. Our data also demonstrate that the Fe‐Si binary eutectic liquid reduces its Si concentration to ∼8 wt% with increasing pressure to 330 GPa. We found that the inner core is not an Fe‐Si‐C‐S alloy but likely includes hydrogen when considering the low DC and the strong enhancement of DSi with increasing liquid C abundance. The present‐day core does not include as much as ∼6 wt% Si, suggesting that at least a part of “missing” Si could be sequestrated elsewhere.
Naphthalene‐Derived Secondary Organic Aerosols Interfacial Photosensitizing Properties
Authors: Wang Xinke , Gemayel Rachel , Baboomian Vahe J. , Li Kangwei , Boreave Antoinette , Dubois Clement , Tomaz Sophie , Perrier Sebastien , Nizkorodov Sergey A. , George Christian
Published: June 2021

We investigated the photosensitizing properties of secondary organic aerosol (SOA) formed during the hydroxyl radical (OH) initiated oxidation of naphthalene. This SOA was injected into an aerosol flow tube and exposed to UV radiation and gaseous volatile organic compounds or sulfur dioxide (SO2). The aerosol particles were observed to grow in size by photosensitized uptake of d‐limonene and β‐pinene. In the presence of SO2, a photosensitized production (0.2–0.3 µg m−3 h−1) of sulfate was observed at all relative humidity (RH) levels. Some sulfate also formed on particles in the dark, probably due to the presence of organic peroxides. The dark and photochemical pathways exhibited different trends with RH, unraveling different contributions from bulk and surface chemistry. As naphthalene and other polycyclic aromatics are important SOA precursors in the urban and suburban areas, these dark and photosensitized reactions are likely to play an important role in sulfate and SOA formation.
How do Climate Modes Shape the Chlorophyll‐a Interannual Variability in the Tropical Atlantic?
Authors: Chenillat Fanny , Illig Serena , Jouanno Julien , Awo Founi Mesmin , Alory Gaël , Brehmer Patrice
Published: June 2021

Chlorophyll‐a concentration (Chl‐a) observed by satellite shows a marked seasonal and interannual variability in the tropical Atlantic. This study analyzes how the remotely sensed surface Chl‐a responds to the leading boreal summer climate modes affecting the interannual tropical Atlantic variability over 1998–2018, corresponding to a positive Atlantic Multidecadal Oscillation phase. We show that the Atlantic Zonal Mode (AZM) and the North Tropical Atlantic Mode (NTAM) significantly drive the interannual surface Chl‐a variability in the equatorial Atlantic, with different timings and contrasted zonal modulation of the cold tongue. The AZM involves remotely forced wave propagations favoring upwelling in the east and Chl‐a modulation in the core of the cold tongue. Instead, the impact of the NTAM is mainly in the west, in response to locally forced pumping that modulates the western extension of the cold tongue. Such conditions can affect the marine food web, inducing significant variations for ecosystem functioning and fisheries.
A Rapid Numerical Method to Constrain 2D Focused Fluid Flow Rates Along Convergent Margins Using Dense BSR‐Based Temperature Field Data
Authors: Kunath Pascal , Chi Wu‐Cheng , Berndt Christian , Liu Char‐Shine
Published: June 2021

Estimates of the sub‐seabed fluid flow rates are important for understanding hydrological budgets, biogeochemical cycles, and physical properties of the sediments. Fluid flow rates and directions, however, are difficult to measure, particularly beneath the seafloor. We developed a rapid method to estimate regional fluid migration rates using an extensive database of seismic reflection profiles taken offshore SW Taiwan. We observe bottom‐simulating reflector (BSR) that deflects toward the seafloor near thrust faults that indicate localized heat flow variations. At these sites, advecting warm pore fluids transport heat to shallower depths and force the BSR shallower. Our 2D steady‐state numerical method quantifies the fluid flow rates required to cause such thermal anomalies. We found that fluid flow rates near the trench of the accretionary wedge range between 0.1 and 16 m3 yr−1 m−1, with slower and faster rates generally associated with slope basin discontinuities and faults, respectively. To evaluate the fluid pattern evolution from subduction to collision, we studied three transects: one along the Manila subduction zone in the south and two in Taiwan's initial collision zone in the north. We quantified the fluid budget and partitioning of fluid flow between focused discharge through faults and diffusive flow through the wedge. Faults in Taiwan's accretionary wedge capture on average 25% of the total dewatering flux in the younger subduction zone and 38.5% in the tectonically mature collision zone. Our method provides estimates of fluid migration rates along convergent plate boundaries, and contributes to our understanding of focused fluid flow processes in many other regions.
The Effect of Resolution on Vertical Heat and Carbon Transports in a Regional Ocean Circulation Model of the Argentine Basin
Authors: Swierczek Stan , Mazloff Matthew R. , Morzfeld Matthias , Russell Joellen L.
Published: June 2021

Simulations of the Argentine Basin have large uncertainties associated with quantities such as air‐sea exchanges of heat and carbon in current generation climate models and ocean reanalysis products. This is due to the complex topography, profound undersampling until recent years, and strong currents and mixing of subpolar and subtropical water masses in the basin. Because mixing of water masses is important here, model resolution is hypothesized to play an important role in estimating ocean quantities and determining overall budgets. We construct three regional ocean models with biogeochemistry at 1/3°, 1/6°, and 1/12° resolutions for the year 2017 to investigate heat and carbon dynamics in the region and determine the effect of model resolution on these dynamics. Initial conditions and boundary forcing from BSOSE (the Biogeochemical Southern Ocean State Estimate (Verdy & Mazloff, 2017), https://doi.org/10.1002/2016JC012650) and atmospheric forcing from ERA5 are used. The models are evaluated for accuracy by comparing output to Argo and BGC‐Argo float profiles, BSOSE, and other reanalyses and mapped products. We then quantify the effect of resolution on model upper ocean heat and carbon transport and the associated air‐sea exchanges. We determine that increasing the resolution from 1/3° to 1/12° enhances the upward vertical transport and surface exchanges of heat but causes no significant effect on surface carbon fluxes despite enhancing downward transport of anomalous DIC.
Calving Multiplier Effect Controlled by Melt Undercut Geometry
Authors: Slater D. A. , Benn D. I. , Cowton T. R. , Bassis J. N. , Todd J. A.
Published: June 2021

Quantifying the impact of submarine melting on calving is central to understanding the response of marine‐terminating glaciers to ocean forcing. Modeling and observational studies suggest the potential for submarine melting to amplify calving (the calving multiplier effect), but there is little consensus as to under what conditions this occurs. Here, by viewing a marine‐terminating glacier as an elastic beam, we propose an analytical basis for understanding the presence or absence of the calving multiplier effect. We show that as a terminus becomes undercut it becomes more susceptible to both serac failure (calving only of ice that is undercut, driven by vertical imbalance) and rotational failure (full‐thickness calving of ice behind the grounding line, driven by rotational imbalance). By deriving analytical stress thresholds for these two forms of calving, we suggest that the dominant of the two calving styles is determined principally by the shape of melt‐undercutting. Uniform undercutting extending from the bed to the waterline promotes serac failure and no multiplier effect, while glaciers experiencing linear undercutting that is greatest at the bed and zero at the waterline are more likely to experience rotational failure and a multiplier effect. Our study offers a quantitative framework for understanding where and when the calving multiplier effect occurs, and, therefore, a route to parameterizing the effect in ice sheet‐scale models.
Multianalyte serology in home-sampled blood enables an unbiased assessment of the immune response against SARS-CoV-2
Authors: Roxhed Niclas , Bendes Annika , Dale Matilda , Mattsson Cecilia , Hanke Leo , Dodig-Crnković Tea , Christian Murray , Meineke Birthe , Elsässer Simon , Andréll Juni , Havervall Sebastian , Thålin Charlotte , Eklund Carina , Dillner Joakim , Beck Olof , Thomas Cecilia E. , McInerney Gerald , Hong Mun-Gwan , Murrell Ben , Fredolini Claudia , Schwenk Jochen M.
Published: June 2021

Serological testing is essential to curb the consequences of the COVID-19 pandemic. However, most assays are still limited to single analytes and samples collected within healthcare. Thus, we establish a multianalyte and multiplexed approach to reliably profile IgG and IgM levels against several versions of SARS-CoV-2 proteins (S, RBD, N) in home-sampled dried blood spots (DBS). We analyse DBS collected during spring of 2020 from 878 random and undiagnosed individuals from the population in Stockholm, Sweden, and use classification approaches to estimate an accumulated seroprevalence of 12.5% (95% CI: 10.3%–14.7%). This includes 5.4% of the samples being IgG+IgM+ against several SARS-CoV-2 proteins, as well as 2.1% being IgG−IgM+ and 5.0% being IgG+IgM− for the virus’ S protein. Subjects classified as IgG+ for several SARS-CoV-2 proteins report influenza-like symptoms more frequently than those being IgG+ for only the S protein (OR = 6.1; p < 0.001). Among all seropositive cases, 30% are asymptomatic. Our strategy enables an accurate individual-level and multiplexed assessment of antibodies in home-sampled blood, assisting our understanding about the undiagnosed seroprevalence and diversity of the immune response against the coronavirus.
High-resolution light field prints by nanoscale 3D printing
Authors: Chan John You En , Ruan Qifeng , Jiang Menghua , Wang Hongtao , Wang Hao , Zhang Wang , Qiu Cheng-Wei , Yang Joel K. W.
Published: June 2021

A light field print (LFP) displays three-dimensional (3D) information to the naked-eye observer under ambient white light illumination. Changing perspectives of a 3D image are seen by the observer from varying angles. However, LFPs appear pixelated due to limited resolution and misalignment between their lenses and colour pixels. A promising solution to create high-resolution LFPs is through the use of advanced nanofabrication techniques. Here, we use two-photon polymerization lithography as a one-step nanoscale 3D printer to directly fabricate LFPs out of transparent resin. This approach produces simultaneously high spatial resolution (29–45 µm) and high angular resolution (~1.6°) images with smooth motion parallax across 15 × 15 views. Notably, the smallest colour pixel consists of only a single nanopillar (~300 nm diameter). Our LFP signifies a step towards hyper-realistic 3D images that can be applied in print media and security tags for high-value goods.
Unravelling cytosolic delivery of cell penetrating peptides with a quantitative endosomal escape assay
Authors: Teo Serena L. Y. , Rennick Joshua J. , Yuen Daniel , Al-Wassiti Hareth , Johnston Angus P. R. , Pouton Colin W.
Published: June 2021

Cytosolic transport is an essential requirement but a major obstacle to efficient delivery of therapeutic peptides, proteins and nucleic acids. Current understanding of cytosolic delivery mechanisms remains limited due to a significant number of conflicting reports, which are compounded by low sensitivity and indirect assays. To resolve this, we develop a highly sensitive Split Luciferase Endosomal Escape Quantification (SLEEQ) assay to probe mechanisms of cytosolic delivery. We apply SLEEQ to evaluate the cytosolic delivery of a range of widely studied cell-penetrating peptides (CPPs) fused to a model protein. We demonstrate that positively charged CPPs enhance cytosolic delivery as a result of increased non-specific cell membrane association, rather than increased endosomal escape efficiency. These findings transform our current understanding of how CPPs increase cytosolic delivery. SLEEQ is a powerful tool that addresses fundamental questions in intracellular drug delivery and will significantly improve the way materials are engineered to increase therapeutic delivery to the cytosol.
A subterranean adaptive radiation of amphipods in Europe
Authors: Borko Špela , Trontelj Peter , Seehausen Ole , Moškrič Ajda , Fišer Cene
Published: June 2021

Adaptive radiations are bursts of evolutionary species diversification that have contributed to much of the species diversity on Earth. An exception is modern Europe, where descendants of ancient adaptive radiations went extinct, and extant adaptive radiations are small, recent and narrowly confined. However, not all legacy of old radiations has been lost. Subterranean environments, which are dark and food-deprived, yet buffered from climate change, have preserved ancient lineages. Here we provide evidence of an entirely subterranean adaptive radiation of the amphipod genusNiphargus, counting hundreds of species. Our modelling of lineage diversification and evolution of morphological and ecological traits using a time-calibrated multilocus phylogeny suggests a major adaptive radiation, comprised of multiple subordinate adaptive radiations. Their spatio-temporal origin coincides with the uplift of carbonate massifs in South-Eastern Europe 15 million years ago. Emerging subterranean environments likely provided unoccupied, predator-free space, constituting ecological opportunity, a key trigger of adaptive radiation. This discovery sheds new light on the biodiversity of Europe.
Defective folate metabolism causes germline epigenetic instability and distinguishes Hira as a phenotype inheritance biomarker
Authors: Blake Georgina E. T. , Zhao Xiaohui , Yung Hong wa , Burton Graham J. , Ferguson-Smith Anne C. , Hamilton Russell S. , Watson Erica D.
Published: June 2021

The mechanism behind transgenerational epigenetic inheritance is unclear, particularly through the maternal grandparental line. We previously showed that disruption of folate metabolism in mice by the Mtrr hypomorphic mutation results in transgenerational epigenetic inheritance of congenital malformations. Either maternal grandparent can initiate this phenomenon, which persists for at least four wildtype generations. Here, we use genome-wide approaches to reveal genetic stability in the Mtrr model and genome-wide differential DNA methylation in the germline of Mtrr mutant maternal grandfathers. We observe that, while epigenetic reprogramming occurs, wildtype grandprogeny and great grandprogeny exhibit transcriptional changes that correlate with germline methylation defects. One region encompasses the Hira gene, which is misexpressed in embryos for at least three wildtype generations in a manner that distinguishes Hira transcript expression as a biomarker of maternal phenotypic inheritance.
Machine learning differentiates enzymatic and non-enzymatic metals in proteins
Authors: Feehan Ryan , Franklin Meghan W. , Slusky Joanna S. G.
Published: June 2021

Metalloenzymes are 40% of all enzymes and can perform all seven classes of enzyme reactions. Because of the physicochemical similarities between the active sites of metalloenzymes and inactive metal binding sites, it is challenging to differentiate between them. Yet distinguishing these two classes is critical for the identification of both native and designed enzymes. Because of similarities between catalytic and non-catalytic  metal binding sites, finding physicochemical features that distinguish these two types of metal sites can indicate aspects that are critical to enzyme function. In this work, we develop the largest structural dataset of enzymatic and non-enzymatic metalloprotein sites to date. We then use a decision-tree ensemble machine learning model to classify metals bound to proteins as enzymatic or non-enzymatic with 92.2% precision and 90.1% recall. Our model scores electrostatic and pocket lining features as more important than pocket volume, despite the fact that volume is the most quantitatively different feature between enzyme and non-enzymatic sites. Finally, we find our model has overall better performance in a side-to-side comparison against other methods that differentiate enzymatic from non-enzymatic sequences. We anticipate that our model’s ability to correctly identify which metal sites are responsible for enzymatic activity could enable identification of new enzymatic mechanisms and de novo enzyme design.
In-depth single-cell analysis of translation-competent HIV-1 reservoirs identifies cellular sources of plasma viremia
Authors: Cole Basiel , Lambrechts Laurens , Gantner Pierre , Noppe Ytse , Bonine Noah , Witkowski Wojciech , Chen Lennie , Palmer Sarah , Mullins James I. , Chomont Nicolas , Pardons Marion , Vandekerckhove Linos
Published: June 2021

Clonal expansion of HIV-infected cells contributes to the long-term persistence of the HIV reservoir in ART-suppressed individuals. However, the contribution from cell clones that harbor inducible proviruses to plasma viremia is poorly understood. Here, we describe a single-cell approach to simultaneously sequence the TCR, integration sites and proviral genomes from translation-competent reservoir cells, called STIP-Seq. By applying this approach to blood samples from eight participants, we show that the translation-competent reservoir mainly consists of proviruses with short deletions at the 5’-end of the genome, often involving the major splice donor site. TCR and integration site sequencing reveal that cell clones with predicted pathogen-specificity can harbor inducible proviruses integrated into cancer-related genes. Furthermore, we find several matches between proviruses retrieved with STIP-Seq and plasma viruses obtained during ART and upon treatment interruption, suggesting that STIP-Seq can capture clones that are responsible for low-level viremia or viral rebound.
Pan-cancer characterization of lncRNA modifiers of immune microenvironment reveals clinically distinct de novo tumor subtypes
Authors: Zhang Zicheng , Yan Congcong , Li Ke , Bao Siqi , Li Lei , Chen Lu , Zhao Jingting , Sun Jie , Zhou Meng
Published: June 2021

The emerging field of long noncoding RNA (lncRNA)-immunity has provided a new perspective on cancer immunity and immunotherapies. The lncRNA modifiers of infiltrating immune cells in the tumor immune microenvironment (TIME) and their impact on tumor behavior and disease prognosis remain largely uncharacterized. In the present study, a systems immunology framework integrating the noncoding transcriptome and immunogenomics profiles of 9549 tumor samples across 30 solid cancer types was used, and 36 lncRNAs were identified as modifier candidates underlying immune cell infiltration in the TIME at the pan-cancer level. These TIME lncRNA modifiers (TIL-lncRNAs) were able to subclassify various tumors into three de novo pan-cancer subtypes characterized by distinct immunological features, biological behaviors, and disease prognoses. Finally, a TIL-lncRNA-derived immune state index (TISI) that was reflective of immunological and oncogenic states but also predictive of patients’ prognosis was proposed. Furthermore, the TISI provided additional prognostic value for existing tumor immunological and molecular subtypes. By applying the TISI to tumors from different clinical immunotherapy cohorts, the TISI was found to be significantly negatively correlated with immune-checkpoint genes and to have the ability to predict the effectiveness of immunotherapy. In conclusion, the present study provided comprehensive resources and insights for future functional and mechanistic studies on lncRNA-mediated cancer immunity and highlighted the potential of the clinical application of lncRNA-based immunotherapeutic strategies in precision immunotherapy.
Microbiologically induced aesthetic and structural changes to dimension stone
Authors: Gaylarde Christine C. , Baptista-Neto Jose Antonio
Published: June 2021

Dimension stone is natural rock prepared for building use. It is rapidly colonised by microorganisms that cause discoloration (mainly cyanobacteria, algae and fungi) and structural damage. Microbial mobilisation of ions leads to new superficial or internal deposits, weakening the structure. Cyanobacteria and fungi may penetrate, filling pores or creating new spaces. Lichens, fungus/phototroph associations, colonise surfaces and damage stone through ingrowing rhizines and acid production. Initial degradation produces conditions suitable for germination of seeds of higher plants and further destruction. Emerging techniques to elucidate stone-cell interactions and control of initial biofilm formation that eventuates in stone disintegration are discussed.
Cellular human tissue-engineered skin substitutes investigated for deep and difficult to heal injuries
Authors: Sierra-Sánchez Álvaro , Kim Kevin H. , Blasco-Morente Gonzalo , Arias-Santiago Salvador
Published: June 2021

Wound healing is an important function of skin; however, after significant skin injury (burns) or in certain dermatological pathologies (chronic wounds), this important process can be deregulated or lost, resulting in severe complications. To avoid these, studies have focused on developing tissue-engineered skin substitutes (TESSs), which attempt to replace and regenerate the damaged skin. Autologous cultured epithelial substitutes (CESs) constituted of keratinocytes, allogeneic cultured dermal substitutes (CDSs) composed of biomaterials and fibroblasts and autologous composite skin substitutes (CSSs) comprised of biomaterials, keratinocytes and fibroblasts, have been the most studied clinical TESSs, reporting positive results for different pathological conditions. However, researchers’ purpose is to develop TESSs that resemble in a better way the human skin and its wound healing process. For this reason, they have also evaluated at preclinical level the incorporation of other human cell types such as melanocytes, Merkel and Langerhans cells, skin stem cells (SSCs), induced pluripotent stem cells (iPSCs) or mesenchymal stem cells (MSCs). Among these, MSCs have been also reported in clinical studies with hopeful results. Future perspectives in the field of human-TESSs are focused on improving in vivo animal models, incorporating immune cells, designing specific niches inside the biomaterials to increase stem cell potential and developing three-dimensional bioprinting strategies, with the final purpose of increasing patient’s health care. In this review we summarize the use of different human cell populations for preclinical and clinical TESSs under research, remarking their strengths and limitations and discuss the future perspectives, which could be useful for wound healing purposes.
First simultaneous detection of electron and positron bunches at the positron capture section of the SuperKEKB factory
Authors: Suwada Tsuyoshi , Rehman Muhammad Abdul , Miyahara Fusashi
Published: June 2021

The direct simultaneous detection of electron and positron bunch signals was successfully performed for the first time with wideband pickups and a detection system at the positron capture section of the SuperKEKB factory. The time interval between the electron and positron bunches, their bunch lengths, and bunch intensities depending on the phase of accelerating structures were measured to investigate their capture process and to maximally optimize the positron intensity. The results show that the time intervals were measured in the range of 135–265 ps, and the line-order switch of the electron and positron bunches in the axial direction was clearly observed as a function of the phase. The positron (electron) intensity was maximized at the optimal phase (180$$^{\circ }$$

∘

shifted from the optimum). These series of measurements have never been experimentally conducted so far. It is demonstrated that the positron intensity can be systematically optimized with this system as functions of beam parameters in multidimensional spaces for any positron capture section.
Changes in soil microbial community and activity caused by application of dimethachlor and linuron
Authors: Medo Juraj , Maková Jana , Medová Janka , Lipková Nikola , Cinkocki Renata , Omelka Radoslav , Javoreková Soňa
Published: June 2021

Soil microorganisms and their activities are essential for maintaining soil health and fertility. Microorganisms can be negatively affected by application of herbicides. Although effects of herbicides on microorganisms are widely studied, there is a lack of information for chloroacetamide herbicide dimethachlor. Thus, dimethachlor and well known linuron were applied to silty-loam luvisol and their effects on microorganisms were evaluated during112 days long laboratory assay. Dimethachlor and linuron were applied in doses 1.0 kg ha−1 and 0.8 kg ha−1 corresponding to 3.33 mg kg−1 and 2.66 mg kg−1 respectively. Also 100-fold doses were used for magnification of impacts. Linuron in 100-fold dose caused minor increase of respiration, temporal increase of soil microbial biomass, decrease of soil dehydrogenase activity, and altered microbial community. Dimethachlor in 100-fold dose significantly increased respiration; microbial biomass and decreased soil enzymatic activities. Microbial composition changed significantly, Proteobacteria abundance, particularly Pseudomonas and Achromobacter genera increased from 7 to 28th day. In-silico prediction of microbial gene expression by PICRUSt2 software revealed increased expression of genes related to xenobiotic degradation pathways. Evaluated characteristics of microbial community and activity were not affected by herbicides in recommended doses and the responsible use of both herbicides will not harm soil microbial community.
Unraveling hidden interactions in complex systems with deep learning
Authors: Ha Seungwoong , Jeong Hawoong
Published: June 2021

Rich phenomena from complex systems have long intrigued researchers, and yet modeling system micro-dynamics and inferring the forms of interaction remain challenging for conventional data-driven approaches, being generally established by scientists with human ingenuity. In this study, we propose AgentNet, a model-free data-driven framework consisting of deep neural networks to reveal and analyze the hidden interactions in complex systems from observed data alone. AgentNet utilizes a graph attention network with novel variable-wise attention to model the interaction between individual agents, and employs various encoders and decoders that can be selectively applied to any desired system. Our model successfully captured a wide variety of simulated complex systems, namely cellular automata (discrete), the Vicsek model (continuous), and active Ornstein–Uhlenbeck particles (non-Markovian) in which, notably, AgentNet’s visualized attention values coincided with the true variable-wise interaction strengths and exhibited collective behavior that was absent in the training data. A demonstration with empirical data from a flock of birds showed that AgentNet could identify hidden interaction ranges exhibited by real birds, which cannot be detected by conventional velocity correlation analysis. We expect our framework to open a novel path to investigating complex systems and to provide insight into general process-driven modeling.
Association between ankle brachial index and development of postoperative intensive care unit delirium in patients with peripheral arterial disease
Authors: Kang Jihee , An Ji Hyun , Jeon Hong Jin , Park Yang Jin
Published: June 2021

Patients with vascular diseases are prone to developing postoperative delirium (POD). Ankle brachial index (ABI) is a non-invasive clinical indicator of lower-extremities peripheral arterial disease (PAD) and has been identified as an indicator of cognitive impairment. We investigated the association between ABI and POD. 683 PAD patients who underwent elective leg arterial bypass surgery between October 1998 and August 2019 were collected for retrospective analysis. Demographic information, comorbidities, preoperative ABI and the Rutherford classification within one month prior to surgery were obtained. POD was assessed using the Confusion assessment method -intensive care unit. Logistic regression and receiver operating characteristics (ROC) curve analysis were used to assess the association between ABI and POD. The mean value of ABI was significantly lower in patients with POD than it was those without POD. Older age, more medical comorbidities, longer length of surgery, decreased ABI, and higher Rutherford class were all significantly associated with POD. The area under ROC (0.74) revealed that ABI below 0.35 was associated with development of POD. Lower preoperative ABI was associated with POD in PAD patients who underwent arterial bypass surgery.
Paired analysis of tumor mutation burden for lung adenocarcinoma and associated idiopathic pulmonary fibrosis
Authors: Yoneshima Yasuto , Iwama Eiji , Matsumoto Shingo , Matsubara Taichi , Tagawa Testuzo , Ota Keiichi , Tanaka Kentaro , Takenoyama Mitsuhiro , Okamoto Tatsuro , Goto Koichi , Mori Masaki , Okamoto Isamu
Published: June 2021

Genetic alterations underlying the development of lung cancer in individuals with idiopathic pulmonary fibrosis (IPF) have remained unclear. To explore whether genetic alterations in IPF tissue contribute to the development of IPF-associated lung cancer, we here evaluated tumor mutation burden (TMB) and somatic variants in 14 paired IPF and tumor samples from patients with IPF-associated lung adenocarcinoma. We also determined TMB for 22 samples of lung adenocarcinoma from patients without IPF. TMB for IPF-associated lung adenocarcinoma was significantly higher than that for matched IPF tissue (median of 2.94 vs. 1.26 mutations/Mb, P = 0.002). Three and 102 somatic variants were detected in IPF and matched lung adenocarcinoma samples, respectively, with only one pair of specimens sharing one somatic variant. TMB for IPF-associated lung adenocarcinoma was similar to that for lung adenocarcinoma samples with driver mutations (median of 2.94 vs. 2.51 mutations/Mb) and lower than that for lung adenocarcinoma samples without known driver mutations (median of 2.94 vs. 5.03 mutations/Mb, P = 0.130) from patients without IPF. Our findings suggest that not only the accumulation of somatic mutations but other factors such as inflammation and oxidative stress might contribute to the development and progression of lung cancer in patients with IPF.
Time–outcome relationship in acute large-vessel occlusion exists across all ages: subanalysis of RESCUE-Japan Registry 2
Authors: Todo Kenichi , Yoshimura Shinichi , Uchida Kazutaka , Yamagami Hiroshi , Sakai Nobuyuki , Kishima Haruhiko , Mochizuki Hideki , Ezura Masayuki , Okada Yasushi , Kitagawa Kazuo , Kimura Kazumi , Sasaki Makoto , Tanahashi Norio , Toyoda Kazunori , Furui Eisuke , Matsumaru Yuji , Minematsu Kazuo , Kitano Takaya , Okazaki Shuhei , Sasaki Tsutomu , Sakaguchi Manabu , Takagaki Masatoshi , Nishida Takeo , Nakamura Hajime , Morimoto Takeshi ,   RESCUE-Japan Registry 2 Investigators, Toyoda Kazunori , Takeuchi Masataka , Morimoto Masafumi , Onda Toshiyuki , Shibata Masunari , Yoshimura Shinichi , Sakai Nobuyuki , Ohta Takahiro , Imai Keisuke , Itabashi Ryo , Ezura Masayuki , Yamashita Taro , Fukawa Norihito , Kimura Naoto , Doijiri Ryosuke , Ohta Hajime , Enomoto Yukiko , Kanbayashi Chisaku , Yamaura Ikuya , Ishihara Hideyuki , Kamiya Yuki , Hayase Makoto , Nii Kouhei , Kobayashi Junya , Yasuda Hiroaki , Kondo Ryushi , Yamamoto Daisuke , Sakaguchi Manabu , Satomi Junichiro , Yagita Yoshiki , Handa Akira , Shindo Atsushi , Hiyama Nagayasu , Toma Naoki , Tsumoto Tomoyuki , Kimura Kazumi , Tsuruta Wataro , Matsumoto Keigo , Kiura Yoshihiro , Yamazaki Takaaki , Hatano Taketo , Matsumoto Yoshihisa , Kojima Takao , Ikeda Norio , Sakamoto Shigeyuki , Ohnishi Hiroyuki , Haraguchi Koichi , Uchiyama Naoyuki
Published: June 2021

Early reperfusion after endovascular thrombectomy is associated with an improved outcome in ischemic stroke patients; however, the time dependency in elderly patients remains unclear. We investigated the time–outcome relationships in different age subgroups. Of 2420 patients enrolled in the RESCUE-Japan Registry 2 study, a study based on a prospective registry of stroke patients with acute cerebral large-vessel occlusion at 46 centers, we analyzed the data of 1010 patients with successful reperfusion after endovascular therapy (mTICI of 2b or 3). In 3 age subgroups (< 70, 70 to < 80, and ≥ 80 years), the mRS scores at 90 days were analyzed according to 4 categories of onset-to-reperfusion time (< 180, 180 to < 240, 240 to < 300, and ≥ 300 min). In each age subgroup, the distributions of mRS scores were better with shorter onset-to-reperfusion times. The adjusted common odds ratios for better outcomes per 1-category delay in onset-to-reperfusion time were 0.66 (95% CI 0.55–0.80) in ages < 70 years, 0.66 (95% CI 0.56–0.79) in ages 70 to < 80 years, and 0.83 (95% CI 0.70–0.98) in ages ≥ 80 years. Early reperfusion was associated with better outcomes across all age subgroups. Achieving early successful reperfusion is important even in elderly patients.
Multivariable mortality risk prediction using machine learning for COVID-19 patients at admission (AICOVID)
Authors: Kar Sujoy , Chawla Rajesh , Haranath Sai Praveen , Ramasubban Suresh , Ramakrishnan Nagarajan , Vaishya Raju , Sibal Anupam , Reddy Sangita
Published: June 2021

In Coronavirus disease 2019 (COVID-19), early identification of patients with a high risk of mortality can significantly improve triage, bed allocation, timely management, and possibly, outcome. The study objective is to develop and validate individualized mortality risk scores based on the anonymized clinical and laboratory data at admission and determine the probability of Deaths at 7 and 28 days. Data of 1393 admitted patients (Expired—8.54%) was collected from six Apollo Hospital centers (from April to July 2020) using a standardized template and electronic medical records. 63 Clinical and Laboratory parameters were studied based on the patient’s initial clinical state at admission and laboratory parameters within the first 24 h. The Machine Learning (ML) modelling was performed using eXtreme Gradient Boosting (XGB) Algorithm. ‘Time to event’ using Cox Proportional Hazard Model was used and combined with XGB Algorithm. The prospective validation cohort was selected of 977 patients (Expired—8.3%) from six centers from July to October 2020. The Clinical API for the Algorithm is http://20.44.39.47/covid19v2/page1.php being used prospectively. Out of the 63 clinical and laboratory parameters, Age [adjusted hazard ratio (HR) 2.31; 95% CI 1.52–3.53], Male Gender (HR 1.72, 95% CI 1.06–2.85), Respiratory Distress (HR 1.79, 95% CI 1.32–2.53), Diabetes Mellitus (HR 1.21, 95% CI 0.83–1.77), Chronic Kidney Disease (HR 3.04, 95% CI 1.72–5.38), Coronary Artery Disease (HR 1.56, 95% CI − 0.91 to 2.69), respiratory rate > 24/min (HR 1.54, 95% CI 1.03–2.3), oxygen saturation below 90% (HR 2.84, 95% CI 1.87–4.3), Lymphocyte% in DLC (HR 1.99, 95% CI 1.23–2.32), INR (HR 1.71, 95% CI 1.31–2.13), LDH (HR 4.02, 95% CI 2.66–6.07) and Ferritin (HR 2.48, 95% CI 1.32–4.74) were found to be significant. The performance parameters of the current model is at AUC ROC Score of 0.8685 and Accuracy Score of 96.89. The validation cohort had the AUC of 0.782 and Accuracy of 0.93. The model for Mortality Risk Prediction provides insight into the COVID Clinical and Laboratory Parameters at admission. It is one of the early studies, reflecting on ‘time to event’ at the admission, accurately predicting patient outcomes.
Association between alterations in plasma metabolome profiles and laminitis in intensively finished Holstein bulls in a randomized controlled study
Authors: Bäßler Sonja Christiane , Kenéz Ákos , Scheu Theresa , Koch Christian , Meyer Ulrich , Dänicke Sven , Huber Korinna
Published: June 2021

Metabolic consequences of an energy and protein rich diet can compromise metabolic health of cattle by promoting a pro-inflammatory phenotype. Laminitis is a common clinical sign, but affected metabolic pathways, underlying pathophysiology and causative relationships of a systemic pro-inflammatory phenotype are unclear. Therefore, the aim of this study was to elucidate changes in metabolome profiles of 20 months old Holstein bulls fed a high energy and protein diet and to identify novel metabolites and affected pathways, associated with diet-related laminitis. In a randomized controlled feeding trial using bulls fed a high energy and protein diet (HEP; metabolizable energy [ME] intake 169.0 ± 1.4 MJ/day; crude protein [CP] intake 2.3 ± 0.02 kg/day; calculated means ± SEM; n = 15) versus a low energy and protein diet (LEP; ME intake 92.9 ± 1.3 MJ/day; CP intake 1.0 ± 0.01 kg/day; n = 15), wide ranging effects of HEP diet on metabolism were demonstrated with a targeted metabolomics approach using the AbsoluteIDQ p180 kit (Biocrates Life Sciences). Multivariate statistics revealed that lower concentrations of phosphatidylcholines and sphingomyelins and higher concentrations of lyso-phosphatidylcholines, branched chain amino acids and aromatic amino acids were associated with an inflammatory state of diet-related laminitis in Holstein bulls fed a HEP diet. The latter two metabolites share similarities with changes in metabolism of obese humans, indicating a conserved pathophysiological role. The observed alterations in the metabolome provide further explanation on the underlying metabolic consequences of excessive dietary nutrient intake.
Comparative untargeted metabolome analysis of ruminal fluid and feces of Nelore steers (Bos indicus)
Authors: Malheiros Jessica Moraes , Correia Banny Silva Barbosa , Ceribeli Caroline , Cardoso Daniel Rodrigues , Colnago Luiz Alberto , Junior Stanislau Bogusz , Reecy James Mark , Mourão Gerson Barreto , Coutinho Luiz Lehmann , Palhares Julio Cesar Pascale , Berndt Alexandre , de Almeida Regitano Luciana Correia
Published: June 2021

We conducted a study to identify the fecal metabolite profile and its proximity to the ruminal metabolism of Nelore steers based on an untargeted metabolomic approach. Twenty-six Nelore were feedlot with same diet during 105 d. Feces and rumen fluid were collected before and at slaughter, respectively. The metabolomics analysis indicated 49 common polar metabolites in the rumen and feces. Acetate, propionate, and butyrate were the most abundant polar metabolites in both bio-samples. The rumen presented significantly higher concentrations of the polar compounds when compared to feces (P < 0.05); even though, fecal metabolites presented an accentuated representability of the ruminal fluid metabolites. All fatty acids present in the ruminal fluid were also observed in the feces, except for C20:2n6 and C20:4n6. The identified metabolites offer information on the main metabolic pathways (higher impact factor and P < 0.05), as synthesis and degradation of ketone bodies; the alanine, aspartate and glutamate metabolisms, the glycine, serine; and threonine metabolism and the pyruvate metabolism. The findings reported herein on the close relationship between the ruminal fluid and feces metabolic profiles may offer new metabolic information, in addition to facilitating the sampling for metabolism investigation in animal production and health routines.