bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Evolution of Plume Fronts in the Rhine Region of Freshwater Influence
Authors: Rijnsburger Sabine , Flores Raúl P. , Pietrzak Julie D. , Horner‐Devine Alexander R. , Souza Alejandro J. , Zijl Firmijn 
Published: June 2021

AbstractThe Rhine region of freshwater influence (ROFI) is strongly stratified, rotational, relatively shallow and has large tides, resulting in a dynamic field of fronts that are formed by multiple processes. We use a 3D numerical model to obtain a conceptual picture of the frontal structure and the processes responsible for generating this multiple front structure in the Rhine ROFI. The horizontal salinity gradient and numerical tracers are used to identify three different types of fronts: outer, inner, tidal plume and relic tidal plume fronts. Tidal plume front (TPF) trajectories together with the tracers demonstrate that TPFs exist for longer than one tidal cycle. A Lagrangian frontogenesis analysis shows that the fronts are strengthened mainly as a result of increased convergence, which is observed to occur at times when tidal straining is large. Additionally the alongshore tidal excursion and the dominance of the tidal currents over the intrinsic frontal propagation speed, trap TPFs within 20 km from the river mouth. Trapping and re‐strengthening maintain several fronts at a time in the mid‐field region, resulting in a multi‐frontal system. The observation of a complex river plume system is expected to be important for cross‐shore exchange, transport and coastal ecology.
The Architecture of the Southern Puna Magmatic System: Integrating Seismic and Petrologic Observations With Geochemical Modeling
Authors: Delph Jonathan R. , Shimizu Kei , Ratschbacher Barbara C. 
Published: June 2021

AbstractImprovements in geochemical, petrologic, and geophysical methods and data have led to a paradigm‐shift in understanding magmatic system architecture away from isolated magmatic chambers toward transcrustal “mushy” magmatic systems. Geochemical and petrologic studies indicate that magma storage and differentiation occurs over a range of depths throughout the crust, while geophysical techniques delineate in situ spatial distributions of melt at similar scales. However, seismic properties are nonunique with respect to composition and melt percentage, and must be integrated with geochemical observations to better understand the architecture and chemical evolution of magmatic systems. The southern Puna Plateau represents a locality where extensive geochemical and seismic data can be combined to investigate the role of depth‐dependent processes in generating compositionally diverse volcanism. By combining geochemical modeling with seismic images of shear‐wave velocity and attenuation, we find that magma storage and differentiation occurs predominantly at two depth ranges: (a) near the base of the crust (>40 km), where shear‐wave velocities are anomalously slow compared to what is expected (<4.0 km/s) and geochemical signatures indicate fractional crystallization and crustal assimilation in the garnet stability field, and (b) in the mid‐crust (∼20 km) beneath the Cerro Galan Caldera, where shear‐wave velocities necessitate the presence of melt (∼2.7 km/s) and europium (Eu) anomalies indicate low‐pressure differentiation. These geochemical and seismic results provide evidence for multi‐level melt evolution and are consistent with petrological features of exposed arcs, whose transcrustal architecture is characterized by discrete and compositionally evolved intrusive bodies in the mid‐crust and a compositionally heterogeneous lower crust.
Relating Far‐Field Coseismic Ionospheric Disturbances to Geological Structures
Authors: Liu Haitao , Zhang Keke , Imtiaz Nadia , Song Qian , Zhang Ying 
Published: June 2021

AbstractClear near‐epicentral coseismic ionospheric disturbances (CIDs) are observed following the Gorkha and May 2015 Nepal earthquakes and only the Gorkha earthquake excited observable far‐field CIDs up to 3,000 km from the epicenter. The near‐epicentral CIDs exhibit concentric fields to the south and north of the epicenter. A north‐south asymmetry of the CIDs is clearly observed in the near‐epicentral area of both earthquakes. The velocity and period of the main part of the near‐epicentral CIDs are ∼1,000 m/s and ∼6 min, respectively. The wavefronts of the far‐field CIDs related to the Gorkha earthquake are mostly straight lines that completely differ from the near‐epicentral CIDs. The horizontal trace of the far‐field CIDs reaches velocities of ∼2.5 km/s based on their distance from the epicenter and the CID arrival time. After identifying the propagation direction of the far‐field CIDs on a series of two‐dimensional (2D) total electron content (TEC) maps, we obtain the real horizontal velocity of far‐field CIDs, which is ∼1.0 km/s, and the period is ∼3 min, which corresponds to that of acoustic waves in the ionosphere. We find a discontinuity of the far‐field CIDs around the Sichuan Basin, which suggests that deep sedimentation can reduce seismic energy coupling into the atmosphere and then the ionosphere. In addition, by introducing a simple acoustic source into the SAMI2 simulation, we show that the large electron density of the background ionosphere and steep inclination of the geomagnetic field are favorable conditions for the generation of detectable CIDs.
Seismic Imaging of the Mw 7.1 Ridgecrest Earthquake Rupture Zone From Data Recorded by Dense Linear Arrays
Authors: Qiu Hongrui , Ben‐Zion Yehuda , Catchings Rufus , Goldman Mark R. , Allam Amir A. , Steidl Jamison 
Published: June 2021

AbstractWe analyze seismograms recorded by four arrays (B1–B4) with 100 m station spacing and apertures of 4–8 km that cross the surface rupture of the 2019 Mw 7.1 Ridgecrest earthquake. The arrays extend from B1 in the northwest to B4 in the southeast of the surface rupture. Delay times between P wave arrivals associated with ∼1,200 local earthquakes and four teleseismic events are used to estimate local velocity variations beneath the arrays. Both teleseismic and local P waves travel faster on the northeast than the southwest side of the fault beneath arrays B1 and B4, but the velocity contrast is less reliably resolved at arrays B2 and B3. We identify several 1–2 km wide low‐velocity zones with much slower inner cores that amplify S waveforms, inferred as damage zones, beneath each array. The damage zones at arrays B2 and B4 also generate fault‐zone head and trapped waves. An automated detector, based on peak ground velocities and durations of high‐amplitude waves, identifies candidate fault‐zone trapped waves (FZTWs) in a localized zone for ∼600 earthquakes at array B4. Synthetic waveform modeling of averaged FZTWs, generated by ∼30 events with high‐quality signals, indicates that the trapping structure at array B4 has a width of ∼300 m, depth of 3–5 km, S wave velocity reduction of ∼20% with respect to the surrounding rock, Q‐value of ∼30, and S wave velocity contrast of ∼4% across the fault (faster on the northeast side). The results show complex fault‐zone internal structures (velocity contrasts and low‐velocity zones) that vary along fault strike.
A Numerical Study of Gravity Waves Propagation Characteristics in the Mesospheric Doppler Duct
Authors: Dong Wenjun , Hickey Michael P. , Zhang Shaodong 
Published: June 2021

AbstractDong et al. (2018,https://doi.org/10.1029/2018JD029190, hereafter D18) employed a compressible model to examine the long‐distance horizontal propagation of gravity waves (GWs) in a stratospheric thermal duct in a two‐dimensional domain. Here, we extend this previous work to explore the ducting of GWs in the mesospheric Doppler duct. While most of the characteristics of the thermal duct described in D18 are found to be operative in the Doppler duct, there are some important differences. The propagation velocity of the fundamental (0th) wave mode is always largest in the Doppler duct and smallest in the thermal duct. We find that regardless of the type of duct (Doppler or thermal duct) the energy dissipation rates of wave modes in the duct region are inversely proportional to their horizontal group velocities. Our results suggest that observations of ducted GWs, particularly those made from multiple observation sites, should reveal characteristics that are germane to the particular duct type. For example, we find that the frequency of the dominant wave mode in the Doppler duct increases with increasing distance from the wave source. This behavior is exactly the opposite of what was obtained for the thermal duct by D18.
Measurable residual disease in chronic lymphocytic leukemia: expert review and consensus recommendations
Authors: Wierda William G. , Rawstron Andrew , Cymbalista Florence , Badoux Xavier , Rossi Davide , Brown Jennifer R. , Egle Alexander , Abello Virginia , Cervera Ceballos Eduardo , Herishanu Yair , Mulligan Stephen P. , Niemann Carsten U. , Diong Colin P. , Soysal Teoman , Suzuki Ritsuro , Tran Hoa T. T. , Wu Shang-Ju , Owen Carolyn , Stilgenbauer Stephan , Ghia Paolo , Hillmen Peter 
Published: June 2021

AbstractAssessment of measurable residual disease (often referred to as “minimal residual disease”) has emerged as a highly sensitive indicator of disease burden during and at the end of treatment and has been correlated with time-to-event outcomes in chronic lymphocytic leukemia. Undetectable-measurable residual disease status at the end of treatment demonstrated independent prognostic significance in chronic lymphocytic leukemia, correlating with favorable progression-free and overall survival with chemoimmunotherapy. Given its utility in evaluating depth of response, determining measurable residual disease status is now a focus of outcomes in chronic lymphocytic leukemia clinical trials. Increased adoption of measurable residual disease assessment calls for standards for nomenclature and outcomes data reporting. In addition, many basic questions have not been systematically addressed. Here, we present the work of an international, multidisciplinary, 174-member panel convened to identify critical questions on key issues pertaining to measurable residual disease in chronic lymphocytic leukemia, review evaluable data, develop unified answers in conjunction with local expert input, and provide recommendations for future studies. Recommendations are presented regarding methodology for measurable residual disease determination, assay requirements and in which tissue to assess measurable residual disease, timing and frequency of assessment, use of measurable residual disease in clinical practice versus clinical trials, and the future usefulness of measurable residual disease assessment. Nomenclature is also proposed. Adoption of these recommendations will work toward standardizing data acquisition and interpretation in future studies with new treatments with the ultimate objective of improving outcomes and curing chronic lymphocytic leukemia.
Cellular and metabolic mechanisms of nutrient actions in immune function
Authors: Newsholme Philip 
Published: June 2021

AbstractVarious nutrients can change cell structure, cellular metabolism, and cell function which is particularly important for cells of the immune system as nutrient availability is associated with the activation and function of diverse immune subsets. The most important nutrients for immune cell function and fate appear to be glucose, amino acids, fatty acids, and vitamin D. This perspective will describe recently published information describing the mechanism of action of prominent nutritional intervention agents where evidence exists as to their action and potency.
Amino acid metabolism and signalling pathways: potential targets in the control of infection and immunity
Authors: Tomé Daniel 
Published: June 2021

AbstractDefences to pathogens such as SarCoV2 in mammals involves interactions between immune functions and metabolic pathways to eradicate infection while preventing hyperinflammation. Amino acid metabolic pathways represent with other antimicrobial agent potential targets for therapeutic strategies. iNOS-mediated production of NO from Arg is involved in the innate inflammatory response to pathogens and NO overproduction can induce hyperinflammation. The two Arg- and Trp-catabolising enzymes Arg1 and IDO1 reduce the hyperinflammation by an immunosuppressive effect via either Arg starvation (for Arg1) or via the immunoregulatory activity of the Trp-derived metabolites Kyn (for IDO1). In response to amino acid abundance mTOR activates the host protein translation and Coronaviruses use this machinery for their own protein synthesis and replication. In contrast GCN2, the sensor of amino acid starvation, activates pathways that restrict inflammation and viral replication. Gln depletion alters the immune response that become more suppressive, by favouring a regulatory T phenotype rather than a Th1 phenotype. Proliferating activated immune cells are highly dependent on Ser, activation and differentiation of T cells need enough Ser and dietary Ser restriction can inhibit their proliferation. Cys is strictly required for T-cell proliferation because they cannot convert Met to Cys. Restricting Met inhibits both viral RNA cap methylation and replication, and the proliferation of infected cells with an increased requirement for Met. Phe catabolism produces antimicrobial metabolites resulting in the inhibition of microbial growth and an immunosuppressive activity towards T lymphocytes.
Visuopathy of prematurity: is retinopathy just the tip of the iceberg?
Authors: Ingvaldsen Sigrid Hegna , Morken Tora Sund , Austeng Dordi , Dammann Olaf 
Published: June 2021

AbstractResearch on retinopathy of prematurity (ROP) focuses mainly on the abnormal vascularization patterns that are directly visible for ophthalmologists. However, recent findings indicate that children born prematurely also exhibit changes in the retinal cellular architecture and along the dorsal visual stream, such as structural changes between and within cortical areas. Moreover, perinatal sustained systemic inflammation (SSI) is associated with an increased risk for ROP and the visual deficits that follow. In this paper, we propose that ROP might just be the tip of an iceberg we call visuopathy of prematurity (VOP). The VOP paradigm comprises abnormal vascularization of the retina, alterations in retinal cellular architecture, choroidal degeneration, and abnormalities in the visual pathway, including cortical areas. Furthermore, VOP itself might influence the developmental trajectories of cerebral structures and functions deemed responsible for visual processing, thereby explaining visual deficits among children born preterm.
Coral mucus rapidly induces chemokinesis and genome-wide transcriptional shifts toward early pathogenesis in a bacterial coral pathogen
Authors: Gao Cherry , Garren Melissa , Penn Kevin , Fernandez Vicente I , Seymour Justin R , Thompson Janelle R , Raina Jean-Baptiste , Stocker Roman 
Published: June 2021

Abstract
Elevated seawater temperatures have contributed to the rise of coral disease mediated by bacterial pathogens, such as the globally distributed Vibrio coralliilyticus, which utilizes coral mucus as a chemical cue to locate stressed corals. However, the physiological events in the pathogens that follow their entry into the coral host environment remain unknown. Here, we present simultaneous measurements of the behavioral and transcriptional responses of V. coralliilyticus BAA-450 incubated in coral mucus. Video microscopy revealed a strong and rapid chemokinetic behavioral response by the pathogen, characterized by a two-fold increase in average swimming speed within 6 min of coral mucus exposure. RNA sequencing showed that this bacterial behavior was accompanied by an equally rapid differential expression of 53% of the genes in the V. coralliilyticus genome. Specifically, transcript abundance 10 min after mucus exposure showed upregulation of genes involved in quorum sensing, biofilm formation, and nutrient metabolism, and downregulation of flagella synthesis and chemotaxis genes. After 60 min, we observed upregulation of genes associated with virulence, including zinc metalloproteases responsible for causing coral tissue damage and algal symbiont photoinactivation, and secretion systems that may export toxins. Together, our results suggest that V. coralliilyticus employs a suite of behavioral and transcriptional responses to rapidly shift into a distinct infection mode within minutes of exposure to the coral microenvironment.
LncRNA CERS6-AS1 promotes proliferation and metastasis through the upregulation of YWHAG and activation of ERK signaling in pancreatic cancer
Authors: Xu Jian , Wang Jie , He Zhiwei , Chen Peng , Jiang Xueyi , Chen Yankun , Liu Xinyuan , Jiang Jianxin 
Published: June 2021

AbstractLncRNAs play essential regulatory roles in pancreatic cancer (PC) tumorigenesis and progression. We aimed to investigate the role of lncRNA CERS6-AS1 in PC. CERS6-AS1 expression was determined in PC tissues and cell lines by PCR analysis. The roles of CERS6-AS1 on proliferation, migration, invasion, and epithelial to mesenchymal transition (EMT) were confirmed via CCK-8 assay, EDU assay, transwell assay, wound healing assay, and western blot assay. Besides, the interaction between CERS6-AS1 and their target genes was verified by luciferase report assays and RIP assays. Animal assays and clinical data analysis were performed to validate the functions in vivo. We found that lncRNA CERS6-AS1 was highly expressed in PC tissues and cells. Additionally, high expression of CERS6-AS1 was obviously associated with poor prognosis. Functional assays demonstrated that CERS6-AS1 downregulation significantly inhibited PC cell growth and migration. Moreover, CERS6-AS1 exerted as a molecular sponge for miR-217-5p (miR-217), and miR-217 was confirmed as a potential target of CERS6-AS1. Subsequently, miR-217 suppressed PC cell proliferation and metastasis by directly targeting YWHAG, which interacted with RAF1 and promoted its phosphorylation, leading to RAF1-mediated ERK signaling activation and translocation of phosphorylated ERK from the cytoplasm to the nucleus. Mechanically, CERS6-AS1 silencing significantly inhibited PC cell proliferation and metastasis via a miR-217/YWHAG/RAF1 signaling axis. CERS6-AS1 exerts as a carcinogen in PC to promote malignant features and behaves as a competitive endogenous RNA for miR-217. We identified CERS6-AS1 as a potential biomarker or therapeutic target to improve PC diagnosis and treatment outcomes.
Marizomib sensitizes primary glioma cells to apoptosis induced by a latest-generation TRAIL receptor agonist
Authors: Boccellato Chiara , Kolbe Emily , Peters Nathalie , Juric Viktorija , Fullstone Gavin , Verreault Maïté , Idbaih Ahmed , Lamfers Martine L. M. , Murphy Brona M. , Rehm Markus 
Published: June 2021

AbstractDue to the absence of curative treatments for glioblastoma (GBM), we assessed the efficacy of single and combination treatments with a translationally relevant 2nd generation TRAIL-receptor agonist (IZI1551) and the blood–brain barrier (BBB) permeant proteasome inhibitor marizomib in a panel of patient-derived glioblastoma cell lines. These cells were cultured using protocols that maintain the characteristics of primary tumor cells. IZI1551+marizomib combination treatments synergistically induced apoptotic cell death in the majority of cases, both in 2D, as well as in 3D spheroid cultures. In contrast, single-drug treatments largely failed to induce noticeable amounts of cell death. Kinetic analyses suggested that time-shifted drug exposure might further increase responsiveness, with marizomib pre-treatments indeed strongly enhancing cell death. Cell death responses upon the addition of IZI1551 could also be observed in GBM cells that were kept in a medium collected from the basolateral side of a human hCMEC/D3 BBB model that had been exposed to marizomib. Interestingly, the subset of GBM cell lines resistant to IZI1551+marizomib treatments expressed lower surface amounts of TRAIL death receptors, substantially lower amounts of procaspase-8, and increased amounts of cFLIP, suggesting that apoptosis initiation was likely too weak to initiate downstream apoptosis execution. Indeed, experiments in which the mitochondrial apoptosis threshold was lowered by antagonizing Mcl-1 re-established sensitivity to IZI1551+marizomib in otherwise resistant cells. Overall, our study demonstrates a high efficacy of combination treatments with a latest-generation TRAIL receptor agonist and the BBB permeant proteasome inhibitor marizomib in relevant GBM cell models, as well as strategies to further enhance responsiveness and to sensitize subgroups of otherwise resistant GBM cases.
A new high protein-to-energy enteral formula with a whey protein hydrolysate to achieve protein targets in critically ill patients: a prospective observational tolerability study
Authors: Tedeschi-Jockers Franziska , Reinhold Simona , Hollinger Alexa , Tuchscherer Daniel , Kiss Caroline , Gantner Lukas , Ledergerber Katrin , Zimmermann Sibylle , Scheuzger Jonas , Huber Jan , Siegemund Martin 
Published: June 2021

Abstract
Objectives
Current guidelines and expert recommendations stress the need to implement enteral feeds with a higher protein-to-energy ratio to meet protein requirements as recommended while avoiding gastrointestinal side effects and energy overfeeding in ICU patients.

Materials and methods
Prospective tolerability study in 18 critically ill patients with a high protein formula (high protein-to-energy (HP:E) formula = Fresubin® Intensive; HPG) compared to a contemporary matched conventional therapy group (CTG). The primary outcome was GI intolerance defined as ≥300 ml daily gastric residual volume (GRV), vomiting, or diarrhea on days 1 and 2. Secondary outcomes were the percentage of patients reaching their protein target on day 4 and overall protein intake.

Results
Groups were comparable regarding demographic characteristics, disease severity, organ failures, mechanical ventilation, and NUTRIC score at baseline. Eighteen patients completed the 4-day feeding period. The number of events of GRV of ≥300 ml/day was equal in both groups (33.3%). The incidence of diarrhea and vomiting was low in the HPG (two patients concerned). EN did not need to be discontinued due to intolerance in any group. Seventy-two percent of patients reached protein targets ≥1.3 g/kgBW/d within 4 days after initiation of enteral feeding, which was superior to the CTG (33%). Post-hoc testing showed group differences of protein intake between HPG and CTG were significant at t = 72 h and t = 96 h. Energy targets were met in both groups.

Conclusion
The HP:E formula containing 33% whey protein hydrolysate is well tolerated in this tolerability study. Due to the HP:E ratio protein targets can be reached faster. Larger randomized trials are needed to confirm preliminary results.

Trial registration
ClinicalTrials.gov Identifier: NCT02678325. Registered 2 May 2016.