bluuebunny/crossref_metadata_2025 huggingface dataset:
Subcellular detection of PEBCA particles in macrophages: combining darkfield microscopy, confocal Raman microscopy, and ToF–SIMS analysis
Authors: Vennemann Antje , Breitenstein Daniel , Tallarek Elke , Mørch Ýrr , Schmid Ruth , Wiemann Martin
Published: February 2022

The detection of biomedical organic nanocarriers in cells and tissues is still an experimental challenge. Here we developed an imaging strategy for the label-free detection of poly (ethylbutyl cyanoacrylate) (PEBCA) particles. Experiments were carried out with phagocytic NR8383 macrophages exposed to non-toxic and non-activating concentrations of fluorescent (PEBCA NR668 and PEBCA NR668/IR), non-fluorescent (PEBCA), and cabazitaxel-loaded PEBCA particles (PEBCA CBZ). Exposure to PEBCA NR668 revealed an inhomogeneous particle uptake similar to what was obtained with the free modified Nile Red dye (NR668). In order to successfully identify the PEBCA-loaded cells under label-free conditions, we developed an imaging strategy based on enhanced darkfield microscopy (DFM), followed by confocal Raman microscopy (CRM) and time-of-flight secondary ion mass spectrometry (ToF–SIMS). Nitrile groups of the PEBCA matrix and PEBCA ions were used as suitable analytes for CRM and ToF–SIMS, respectively. Masses found with ToF–SIMS were further confirmed by Orbitrap-SIMS. The combined approach allowed to image small (< 1 µm) PEBCA-containing phagolysosomes, which were identified as PEBCA-containing compartments in NR8383 cells by electron microscopy. The combination of DFM, CRM, and ToF–SIMS is a promising strategy for the label-free detection of PEBCA particles.

Graphical Abstract
When Doctors and AI Interact: on Human Responsibility for Artificial Risks
Authors: Verdicchio Mario , Perin Andrea
Published: February 2022

A discussion concerning whether to conceive Artificial Intelligence (AI) systems as responsible moral entities, also known as “artificial moral agents” (AMAs), has been going on for some time. In this regard, we argue that the notion of “moral agency” is to be attributed only to humans based on their autonomy and sentience, which AI systems lack. We analyze human responsibility in the presence of AI systems in terms of meaningful control and due diligence and argue against fully automated systems in medicine. With this perspective in mind, we focus on the use of AI-based diagnostic systems and shed light on the complex networks of persons, organizations and artifacts that come to be when AI systems are designed, developed, and used in medicine. We then discuss relational criteria of judgment in support of the attribution of responsibility to humans when adverse events are caused or induced by errors in AI systems.
From Responsibility to Reason-Giving Explainable Artificial Intelligence
Authors: Baum Kevin , Mantel Susanne , Schmidt Eva , Speith Timo
Published: February 2022

We argue that explainable artificial intelligence (XAI), specifically reason-giving XAI, often constitutes the most suitable way of ensuring that someone can properly be held responsible for decisions that are based on the outputs of artificial intelligent (AI) systems. We first show that, to close moral responsibility gaps (Matthias 2004), often a human in the loop is needed who is directly responsible for particular AI-supported decisions. Second, we appeal to the epistemic condition on moral responsibility to argue that, in order to be responsible for her decision, the human in the loop has to have an explanation available of the system’s recommendation. Reason explanations are especially well-suited to this end, and we examine whether—and how—it might be possible to make such explanations fit with AI systems. We support our claims by focusing on a case of disagreement between human in the loop and AI system.
Human immunodeficiency virus-1 Tat exerts its neurotoxic effects by downregulating Sonic hedgehog signaling
Authors: khan Irfan A. , Worrad Arthur H. , Singh Meera V. , Maggirwar Sanjay B. , Singh Vir B.
Published: February 2022

We previously showed that HIV-1 can alter the expression of tight junction proteins by downregulating Sonic hedgehog (Shh) signaling, thereby disrupting blood–brain barrier (BBB) integrity. In this study, we employed a conditional, CNS specific, Tat transgenic murine model to investigate if HIV-Tat exerts its neurotoxic effects by downregulating Shh signaling. Results indicate that Tat + mice exhibit significantly reduced expression of Shh and Gli1. HIV-Tat induced downregulation of Shh signaling correlated with disruption of BBB function and induced infiltration of peripheral leukocytes into the brain tissue. Further, our in vivo and in vitro experiments suggest that activation of Shh signaling can rescue detrimental effects of Tat on endothelial function by inducing the expression of junctional proteins and by decreasing the levels of inflammatory cytokines/chemokines.
Weighted superposition operators on Fock spaces
Authors: Mengestie Tesfa
Published: February 2022

We characterize all pairs of entire functions $$(u,\psi )$$

(
u
,
ψ
)

for which the induced weighted superposition operator $$S_{(u,\psi )}$$

S

(
u
,
ψ
)

transforms one Fock space into another Fock space. Further analytical structures like boundedness and Lipschitz continuity of $$S_{(u,\psi )}$$

S

(
u
,
ψ
)

are described. We, in particular, show the Fock spaces support no compact weighted superposition operator.
Sonographic normal values for the cross-sectional area of the ulnar nerve: a systematic review and meta-analysis
Authors: Boers Nadine , Martin Enrico , Mazur Marc , Krijgh David D. , Vlak Monique H. M. , de Ruiter Godard C. W. , Goedee H. Stephan , Coert J. Henk
Published: February 2022

Purpose

Nerve size is a commonly used sonographic parameter when assessing suspected entrapment of the ulnar nerve. We aimed to create a robust set of normal values, based on a critical review of published normal values.

Methods

We performed a systematic evaluation of studies on normal ulnar nerve sizes, identified in PubMed, Embase, and Cochrane databases. Using meta-analyses, we determined pooled mean cross-sectional area (CSA) values for different anatomical locations of the ulnar nerve throughout the arm. Subgroup analyses were performed for gender, probe frequency, in- or exclusion of diabetic patients, position of the elbow and Asian versus other populations.

Results

We identified 90 studies of which 77 studies were included for further analyses after quality review, resulting in data from 5772 arms of 3472 participants. Subgroup analyses show lower CSA values at at the wrist crease and proximal to the wrist crease when using low frequency probes (< 15 MHz) and at the wrist crease, proximal to the wrist crease, proximal forearm and the distal upper arm in Asians. CSA values were lower when in flexed position compared to extended position for the cubital tunnel inlet only. No difference was found for gender.

Conclusions

Our systematic review provides a comprehensive set of normal values at sites along the entire length of the ulnar nerve. This provides a foundation for clinical practise and upon which future studies could be more systematically compared.
Application of Andersen–Newman model to assess cataract surgery uptake among older Australian women: findings from the Australian Longitudinal Study on Women’s Health (ALSWH)
Authors: Hambisa Mitiku Teshome , Dolja-Gore Xenia , Byles Julie
Published: February 2022

Introduction

Although Cataract Surgery Rate is increasing, the availability of surgery is outstripped by the increasing number of cataract cases as populations age.

Aim

The study aimed to identify factors associated with cataract surgery uptake in terms of predisposing, enabling, and need factors in very old Australian women.

Method

This study used ALSWH data included 6229 women aged 79–84 to 85–90 years. Women were asked whether they had undergone eye surgery (including cataracts) three years prior to each survey. Generalised estimating equation modelling was used to determine factors associated with these surgeries.

Result

At baseline (2005), more than half of the participants either had undergone surgery (43.5%) or had unoperated cataracts (7.6%). Increasing age (AOR = 1.11, 95% CI = 1.07, 1.15) and being current or ex-smokers (AOR = 1.15, 95% CI = 1.03, 1.29) were associated with higher odds of cataract surgery (predisposing factors). Women who had private health insurance had 27% higher odds of having surgery (AOR = 1.27, 95% CI = 1.16, 1.39) (enabling factor). Need factors of more General Practitioner visits (AOR = 1.16, 95% CI = 1.09, 1.25) and skin cancer (AOR = 1.09, 95% CI = 1.01, 1.17) also increased the odds of cataract surgery. Women who had no difficulty seeing newspaper print were more likely to have had cataract surgery (AOR = 1.35, 95% CI = 1.23, 1.48).

Conclusion

Need factors are the major drivers of cataract surgery; however, predisposing and enabling factors also play a role, including access to private health insurance. This finding indicates some inequity regarding access to cataract surgery in the Australian setting.
Race/Ethnicity may be an Important Predictor of Life Expectancy in Localized Prostate Cancer Patients: Novel Analyses Using Social Security Administration Life Tables
Authors: Würnschimmel Christoph , Nocera Luigi , Wenzel Mike , Ruvolo Claudia Collà , Tian Zhe , Saad Fred , Briganti Alberto , Shariat Shahrokh F. , Mirone Vincenzo , Chun Felix K. H. , Tilki Derya , Graefen Markus , Karakiewicz Pierre I.
Published: February 2022

Purpose

To test the effect of race/ethnicity on Social Security Administration (SSA) life tables’ life expectancy (LE) predictions in localized prostate cancer (PCa) patients treated with either radical prostatectomy (RP) or external beam radiotherapy (EBRT). We hypothesized that LE will be affected by race/ethnicity.

Patients and Methods

We relied on the 2004–2006 Surveillance, Epidemiology, and End Results database to identify D’Amico intermediate- and high-risk PCa patients treated with either RP or EBRT. SSA life tables were used to compute 10-year LE predictions and were compared to OS. Stratification was performed according to treatment type (RP/EBRT) and race/ethnicity (non-Hispanic White, non-Hispanic Black, Hispanic/Latino, and Asian).

Results

Of 55,383 assessable patients, 40,490 were non-Hispanic White (RP 49.3% vs. EBRT 50.7%), 7194 non-Hispanic Black (RP 41.3% vs. EBRT 50.7%), 4716 Hispanic/Latino (RP 51.0% vs. EBRT 49.0%) and 2983 were Asian (RP 41.6% vs. EBRT 58.4%). In both RP and EBRT patients, OS exceeded life tables’ LE predictions, except for non-Hispanic Blacks. However, in RP patients, the magnitude of the difference was greater than in EBRT. Moreover, in RP patients, OS of non-Hispanic Blacks virtually perfectly followed predicted LE. Conversely, in EBRT patients, the OS of non-Hispanic Black patients was worse than predicted LE.

Conclusions

When comparing SEER-derived observed OS with SSA life table–derived predicted life expectancy, we recorded a survival disadvantage in non-Hispanic Black RP and EBRT patients, which was not the case in the three other races/ethnicities (non-Hispanic Whites, Hispanic/Latinos, and Asians). This discrepancy should ideally be confirmed within different registries, countries, and tumor entities. Furthermore, the source of these discrepant survival outcomes should be investigated and addressed by health care politics.
Development of Cold-Bonded Briquettes Using By-Product-Based Ettringite Binder from Ladle Slag
Authors: Abdelrahim Ahmed , Nguyen Hoang , Omran Mamdouh , Kinnunen Paivo , Iljana Mikko , Illikainen Mirja , Fabritius Timo
Published: February 2022

The recycling of steel plant side streams through cold-bonded briquettes has become quite common. However, Portland cement is mainly used as a binder in the briquettes, contributing significantly to the energy consumption, costs, and carbon footprint associated with the production of cold-bonded briquettes. This paper reports on a more sustainable method for side stream recycling that involves replacing cement with an ettringite-based binder. Ettringite binders develop early high strength and mainly consist of ladle slag, another side stream of the industry. Here, the ettringite-based binder is assessed in terms of its mechanical and thermal properties against a reference briquette made using the conventional technique. Three different briquette types are produced using several side stream materials and varying ettringite-based binder content. Briquettes produced using 15% and higher ettringite-based binder content exhibited excellent mechanical properties within a shorter curing period compared to conventional used binder. Moreover, the ettringite-based binder briquettes exhibited a better swelling behavior to conventional cement briquettes under conditions simulating a blast furnace.

Graphical Abstract
Severe weight loss in a hypothyroid patient as an acute presentation of autoimmune polyglandular syndrome type II
Authors: Silajdzija Elvira , Bliddal Sofie , Borgwardt Line , Rossing Maria , Jarløv Anne , Nielsen Claus Henrik , Feldt-Rasmussen Ulla
Published: February 2022

Background

Autoimmune disease, including autoimmune thyroid disease, with uncharacteristic symptoms can be due to additional severe disease. We report a life-threatening debut of autoimmune polyglandular syndrome type II (APS II) defined as Addison’s disease combined with autoimmune diabetes and/or thyroid disease.

Patient findings

A 33-year-old male with newly diagnosed hypothyroidism was referred to a tertiary center due to fatigue and 20-kg rapid weight loss. Malignancy was excluded. After a gastroscopy, he developed Addison’s crisis; he was admitted to our hospital and stabilized. Final diagnoses included Hashimoto’s thyroiditis, Addison’s disease, vitiligo, and pernicious anemia. Whole genome sequencing found no genetic variants associated with component diseases. Human leukocyte antigen typing revealed DR3/DR4 and DQ8/DQ2 heterozygosity associated with APS II.

A patient with Hashimoto’s thyroiditis and weight loss presented with Addison’s crisis and was diagnosed with APS II.

Conclusions

Awareness of potential polyautoimmunity in clinical evaluation of patients with thyroid disease improves diagnosis and can be lifesaving.
Sustainable shotcrete production with waste glass aggregates
Authors: Serati Mehdi , Jakson Niki , Asche Harry , Basireddy Sai , Malgotra Gautam
Published: February 2022

This study employs statistical and experimental procedures to assess the applicability of crushed waste glass to replace natural sand in shotcrete production for use in tunneling, mining and excavation industries as a support system. Mechanical strength under different uniaxial and biaxial load combinations, fracture properties, and ultra-high-speed photography of the crack growth mode in the newly developed shotcrete mixes were studied and compared against the control mix at 0% waste glass inclusion. Results suggest that shotcrete mixes containing synthetic glass aggregates exhibit similar or higher strength properties (compared with conventional shotcrete with natural aggregates) at early and late ages in both fresh and hardened shotcrete samples. Under biaxial stress conditions, in particular, the new glass shotcrete designs demonstrate a higher load-bearing capacity of up to 35% increase. Compared to conventional shotcrete, replacing sand with recycled glass aggregates further exhibited the need for less water and binder consumption owing to the glass water-reducing effect. This in return could leave more water available for improved workability in the mixture hence producing a more cost-effective and eco-friendly shotcrete product. From the results, no impairment of performance was recorded by substituting sand with crushed waste glass even at a high substitution percentage of up to 100%; suggesting high improvement potential of crushed waste glass re-use in the shotcrete industry.
Operational behaviour of graded diamond grinding wheels for end mill cutter machining
Authors: Denkena Berend , Bergmann Benjamin , Raffalt Daniel
Published: February 2022

The varying related material removal rate during deep grinding of cemented carbide end mill cutters results in an unevenly wear of the grinding wheel. This study therefore presents a simulation-based model for the load-adjusted design of grinding wheels to achieve balanced radial wear, as well as an evaluation of this model. The related material removal rate along the width of the grinding wheel is determined by a Dexel based material removal simulation for different end mill geometries. Based on these results an equation is derived to adapt the abrasive layer properties to the local load differences. Three grinding wheels with different types of gradients are then manufactured by a grinding tool manufacturer based on this equation. These and two grinding wheels with constant abrasive layer properties are used for deep grinding of ten end mills each. Afterwards the radial wear of each grinding wheel is measured by a confocal microscope. An analysis of the cutting edge chipping is done to evaluate the influence on the graded grinding wheels on the cutting edge quality. It was found that a reduction of the wear difference over the grinding wheel width of 52% and an improved cutting edge quality can be achieved by using graded grinding tools. This allows the time intervals between dressing steps to be increased without compromising the accuracy of the grinding process, thus also increasing its productivity. Finally, this article shows that the presented model allows for a more balanced wear behaviour, but has to be extended by considering further factors influencing radial wear.
Evaluation of the Hydraulic Conductivity of Geosynthetic Clay Liners
Authors: Hou Juan , Teng Yuyang , Bao Shifen , Li Hao , Liu Lei
Published: February 2022

The hydraulic conductivity of geosynthetic clay liners (GCLs) is not fully understood and certain gaps in knowledge are still present, such as the effect of coupled mechanical and chemical processes. The current study aimed to develop a simplified mathematical model to predict the hydraulic conductivity of GCLs, particularly regarding the coupled effects of mechanical and chemical processes. Based on Darcy's Law and Poiseuille’s Law, the method combines diffuse double layer (DDL) theory and fractal theory. External factors such as confining pressure and the concentration of the permeating solution, and inherent properties such as exchangeable cations, ionic radius, montmorillonite surface fractal dimension, the distance between two montmorillonite layers (m) after swelling at the exchangeable cation i (i denotes the primary exchangeable cations, such as Na+, Ca2+, K+, and Mg2+ in bentonite), density, and coefficient of viscosity of interlayer water between two montmorillonite layers, were considered. The proposed theoretical model gave relatively accurate predictions. A practical estimate of GCL hydraulic conductivity was also derived. The predictions were compared with experimental results and good qualitative agreement was found. From the experimental results, the proposed prediction model has a maximum deviation of ~1:10–10:1, and the empirical model has a mean deviation of ~1:15–15:1.
Antiviral drug research for Japanese encephalitis: an updated review
Authors: Joe Shaun , Salam Abdul Ajees Abdul , Neogi Ujjwal , N Naren Babu , Mudgal Piya Paul
Published: February 2022

Japanese encephalitis (JE) caused by the Japanese encephalitis virus (JEV) is one of Asia's most common viral encephalitis. JEV is a flavivirus, common in rural and sub-urban regions of Asian countries. Although only 1% of JEV-infected individuals develop JE, there is a 20–30% chance of death among these individuals and possible neurological sequelae post-infection. No licensed anti-JE drugs are currently available, despite extensive efforts to develop them. Literature search was performed using databases such as PubMed Central, Google Scholar, Wiley Online Library, etc. using keywords such as Japanese encephalitis virus, antiviral drugs, antiviral drug screening, antiviral drug targets, etc. From around 230 papers/abstracts and research reviews retrieved and reviewed for this study, approximately 180 most relevant and important ones have been cited. Different approaches in drug testing and various antiviral drug targets explored so far have been thoroughly searched from the literature and compiled, besides addressing the future perspectives of the antiviral drug development strategies. Although the development of effective anti-JE drugs is an urgent issue, only supportive care is currently available. Recent advancements in understanding the biology of infection and new drug targets have been promising improvements. Despite hindrances such as the unavailability of a proper drug delivery system or a treatment regimen irrespective of the stage of infection, several promising anti-JE candidate molecules are in different phases of clinical trials. Nonetheless, efficient therapy against JEV is expected to be achieved with drug combinations and a highly targeted drug delivery system soon.

Graphical abstract
Structure of Pc 5 Compressional Waves Observed in the Duskside Outer Magnetosphere: MMS Observations
Authors: Tian Anmin , Degeling Alexander W. , Park Jong‐Sun , Shi Quanqi , Nowada Motoharu , Pitkänen Timo , Li Wenya , Xiao Chao
Published: February 2022

The geometrical structure of the Pc 5 compressional wave is important in judging its generation mechanism and the wave‐particle interaction process. In this work, 117 magnetic troughs (where magnetic field strength transiently decreases) identified from 50 Pc 5 compressional wave events in the duskside (15.5–18.5 local time) magnetosphere are studied based on the Magnetospheric Multiscale (MMS) data. We derived the three dimensional geometry of the magnetic trough by including the normal and velocity information at its boundaries from the multi‐spacecraft analysis method. The magnetic trough has a magnetic bottle shape along the magnetic field line with the most probable center (with weakest magnetic field) located at θ =  , while the widest part of the magnetic bottle located around θ (θ denotes the angle between spacecraft position vector and the ambient magnetic field). The cross section of the magnetic trough is eccentric and has a “wedge‐like” shape whose average open angle is ∼23° toward radial outward. It is found that the radial component of the current density is the dominant one at the boundaries, and the value is generally proportional to the depth of the magnetic trough. The generation of these Pc 5 compressional waves can be attributed to the drift Alfvén ballooning mirror instability. This work reveals the possible changes of magnetic field configuration caused by the Pc 5 compressional wave in the magnetosphere and may bring new ideas to the interaction way between wave field and ring current particles.
Categorizing MHD Discontinuities in the Inner Heliosphere by Utilizing the PSP Mission
Authors: Liu Y. Y. , Fu H. S. , Cao J. B. , Yu Y. , Liu C. M. , Wang Z. , Guo Z. Z. , He R. J.
Published: February 2022

The interplanetary discontinuities (IDs) have been widely observed in astrophysical and space plasmas, while their characteristics and evolutions within 0.3 AU are still unclear due to the limitation of spacecraft orbits in previous missions. Here, we report three ID events, including a rotational discontinuity (RD), a tangential discontinuity (TD), and a suspected contact discontinuity (CD), detected by the Parker Solar Probe in a previously unexplored region of the heliosphere as close to the Sun as 0.13 AU. By the combination of the minimum variance analysis technique, the Walén relation and the continuity condition of the electric field, the ID orientations, propagations, and thicknesses are determined, showing a smaller typical ID thickness on the order of 100 km therein. Automated event selection using a magnetic field change threshold criterion is conducted with the PSP field data on Orbits 4 and 5. In total, 3,948 IDs are collected, yielding a ratio of . The IDs within 0.4 AU account for 87% of the total IDs, resulting in sharp ID occurrence rate decrease with heliocentric distance, from ∼140 days−1 for RDs and ∼8 days−1 for TDs at 0.13 AU to about 1 day−1 for both RDs and TDs at r > 0.6 AU. Within 0.3 AU, the RDs with tiny propagation angles, i.e., the angles between the magnetic fields and the RD normals, predominate in all kinds of IDs. We further analyze the jump conditions of these IDs statistically, and find that the changes in magnetic fields and particle parameters are theoretically consistent.
Interhemispheric Asymmetries in Magnetosphere and Ionosphere Magnetic Field Residuals Between Swarm Observations and Earth Magnetic Field Models
Authors: Shi Yining , Moldwin Mark B.
Published: February 2022

We present a statistical study of magnetic field vector residual between Swarm observations and two Earth magnetic field models: the 13th generation International Geomagnetic Reference Field (IGRF) model and the CHAOS‐7 model. Statistics of these residuals are important for estimating potential errors for satellite operations when using Earth magnetic models as a reference, as well as for magnetosphere‐ionosphere‐thermosphere studies examining energy input into the system. Magnetic field residuals are calculated as vector differences between observations and model estimation at Swarm satellite positions from 2014 to 2020. Magnetic field residuals for both models increase as geomagnetic activity level increases, and the largest magnitude of vector difference can be around 1800 nT with relatively small angle differences. The CHAOS‐7 model shows lower magnetic field residuals compared to IGRF‐13. North‐south hemispheric asymmetries are seen in magnetic field residuals for high Kp values larger than 6 with the southern hemisphere (SH) having more frequent occurrence of magnetic field residuals larger than 300 nT, especially during SH summer. Most large residual values appear in the high‐latitude region with SH seeing additional large residuals around the South Atlantic Anomaly region. Midnight and noon sectors show the strongest interhemispheric asymmetries. The northern hemisphere shows more frequent occurrence of large residuals above 75° magnetic latitude throughout all local times compared to the SH. Identifying asymmetries in large magnetic residuals under high geomagnetic activity levels is helpful for studying the difference in response to ionospheric disturbances in the two hemispheres.
Spatiotemporal Variations of Shallow Very Low Frequency Earthquake Activity Southeast Off the Kii Peninsula, Along the Nankai Trough, Japan
Authors: Takemura Shunsuke , Obara Kazushige , Shiomi Katsuhiko , Baba Satoru
Published: February 2022

Cross‐correlation analysis was applied to long‐term onshore broadband records from April 2004 to March 2021 to detect and relocate shallow very low frequency earthquakes (VLFEs) southeast off the Kii Peninsula, along the Nankai Trough, Japan. We then determined the moment rate functions of detected shallow VLFEs using the Monte Carlo‐based simulated annealing method. According to this new comprehensive catalog, shallow VLFEs are widespread beneath the accretionary prism toe, but shallow VLFEs with large cumulative moments are localized around the western edge of the paleo‐Zenisu Ridge, which is subducted beneath southeast off the Kii Peninsula. Our results from the long‐term shallow VLFE catalog are well consistent with previous studies in this region, suggesting that heterogeneous structures and stress conditions due to the subducted paleo‐Zenisu Ridge promote the occurrence of shallow slow earthquakes. The relocated shallow VLFE epicenters illustrated three major episodes characterized by a similar activity area and five minor episodes characterized by different areas. The three major episodes exhibited slow frontal migration with different initiation locations, directions, and speeds, as well as several rapid reverse migrations. Episodes of minor activity were distributed in different locations within part of the area of major activity. Different patterns of shallow VLFE migration could reflect temporal changes in the pore‐fluid distribution or stress conditions of the plate boundary.
New Insights Into the Recent Magma Dynamics Under Campi Flegrei Caldera (Italy) From Petrological and Geochemical Evidence
Authors: Buono G. , Paonita A. , Pappalardo L. , Caliro S. , Tramelli A. , Chiodini G.
Published: February 2022

The Campi Flegrei caldera is considered the most dangerous volcano in Europe and is currently in a new phase of unrest (started in 2000 and still ongoing) that has persisted intermittently for several decades (main crisis occurred from 1950 to 1952, 1970–1972, and 1982–1984). Here, by combining the petrological and geochemical data collected in recent decades with numerical simulations, we place new constraints on the source(s) of the current dynamics of the volcano. In particular, we show that the measured (N2‐He‐CO2) geochemical changes at the fumaroles of Solfatara hydrothermal site are the result of massive (about 3 km3) magma degassing in the deep portion (≥200 MPa, 8 km of depth) of the plumbing system. This degassing mechanism would be able to flood the overlying hydrothermal system with hot gas, thus heating and fracturing the upper crust inducing shallow seismicity and deformation. This implies that the deep magma transfer process (≥8 km) has been decoupled from the source of deformation and seismicity, localized in the first kilometers (0–4 km) of caldera‐filling rocks. This information on magma transfer depth can have important implications for defining the best monitoring strategies and for forecasting a future eruption. Finally, this study highlights how petrological and geochemical data allow us to explore the dynamics of the deep portion of the plumbing system and thus trace the occurrence of recharge episodes, in a portion of the ductile lower crust where magma transfer occurs in the absence of earthquakes.
Frontal Dynamics in the Alboran Sea: 1. Coherent 3D Pathways at the Almeria‐Oran Front Using Underwater Glider Observations
Authors: Zarokanellos Nikolaos D. , Rudnick Daniel L. , Garcia‐Jove Maximo , Mourre Baptiste , Ruiz Simon , Pascual Ananda , Tintoré Joaquin
Published: February 2022

Ocean fronts are areas that can support phytoplankton production through fertilization in the sunlit layer and the subduction of biogeochemical properties from the surface to the interior of the ocean. The Almeria‐Oran (AO) front is formed from the juxtaposition of fresh inflowing Atlantic waters and more saline re‐circulating Mediterranean waters. A fleet of three gliders flying in parallel lines was deployed across the AO to obtain observations in the CALYPSO project. These observations were combined with remote sensing and modeling simulations, thus providing a novel approach to identifying the three‐dimensional transport and the submesoscale across‐front circulation. The resulting 33 cross‐front sections reveal spatial and temporal changes in the frontal boundary, with isopycnals steepening and/or relaxing. The observations revealed strong horizontal density gradients (up to ∼1.4 kg m−3) and the spatial variability was observed over different length scales (∼10–45 km). The potential vorticity decreased across the front due to the vorticity component in the horizontal density gradient direction. The predominant cyclonic relative vorticity on the dense side of the AO is associated with downwelling processes. The biogeochemical observations also suggest vertical transport along coherent pathways through baroclinic instability. Phytoplankton biomass enhancement occurs as a result, and is subducted below the euphotic layer. The observed oxygen filaments show upwelling and downwelling, providing a mechanism for oxygenating deeper layers and reducing the ventilation of deep low‐oxygenated waters. Understanding the mechanisms of vertical transport can help us evaluate the dynamics of ocean fronts and their impacts on biological carbon storage.
Layered Ejecta Craters in the Candidate Landing Areas of China's First Mars Mission (Tianwen‐1): Implications for Subsurface Volatile Concentrations
Authors: Niu Shengli , Zhang Feng , Di Kaichang , Gou Sheng , Yue Zongyu
Published: February 2022

One important scientific objective of China's first Mars mission (Tianwen‐1) is to investigate the martian surface soil characteristics and water‐ice distribution. Layered ejecta craters (LECs) on Mars are characterized by their fluidized ejecta deposits which have been interpreted to indicate volatiles in the substrate where the impact occurred. Thus, they have potential to serve as important planetary exploration sites/targets of geological significance. In this study, we estimated the absolute model ages (AMAs) of 68 LECs with diameters >4 km using the Context Camera (an instrument onboard the Mars Reconnaissance Obiter, MRO) images in the two candidate landing areas of Tianwen‐1 mission, aiming to reveal temporal‐spatial variation of the regional subsurface volatiles, in particular water ice. The results from a combination of the derived AMAs and the ejecta mobility (EM) values for the southern Utopia‐Isidis Planitia (SUIP) and southern Chryse Planitia (SCP) show that the LECs in both regions plausibly have formed throughout the Amazonian and Hesperian periods. However, the subsurface volatile concentrations might have undergone different evolution histories: SUIP shows a relatively stable trend with time, while there seems a general downward trend in SCP. The presence of the fresh ∼1.5‐km‐diameter LECs suggests that volatile concentrations might have been at depth less than 150 m. We conclude with a discussion of recommendations for Tianwen‐1 and future explorations that have the ability to effectively detect any signs of past and present water/ice on Mars, which contain a wealth of information of past and recent climate.
Controls on Larsen C Ice Shelf Retreat From a 60‐Year Satellite Data Record
Authors: Wang Shujie , Liu Hongxing , Jezek Kenneth , Alley Richard B. , Wang Lei , Alexander Patrick , Huang Yan
Published: February 2022

Rapid retreat of the Larsen A and B ice shelves has provided important clues about the ice shelf destabilization processes. The Larsen C Ice Shelf, the largest remaining ice shelf on the Antarctic Peninsula, may also be vulnerable to future collapse in a warming climate. Here, we utilize multisource satellite images collected over 1963–2020 to derive multidecadal time series of ice front, flow velocities, and critical rift features over Larsen C, with the aim of understanding the controls on its retreat. We complement these observations with modeling experiments using the Ice‐sheet and Sea‐level System Model to examine how front geometry conditions and mechanical weakening due to rifts affect ice shelf dynamics. Over the past six decades, Larsen C lost over 20% of its area, dominated by rift‐induced tabular iceberg calving. The Bawden Ice Rise and Gipps Ice Rise are critical areas for rift formation, through their impact on the longitudinal deviatoric stress field. Mechanical weakening around Gipps Ice Rise is found to be an important control on localized flow acceleration and the propagation of two rifts that caused a major calving event in 2017. Capturing the time‐varying effects of rifts on ice rigidity in ice shelf models is essential for making realistic predictions of ice shelf flow dynamics and instability. In the context of the Larsen A and Larsen B collapses, we infer a chronology of destabilization processes for embayment‐confined ice shelves, which provides a useful framework for understanding the historical and future destabilization of Antarctic ice shelves.
Spatio‐Temporal Hourly and Daily Ozone Forecasting in China Using a Hybrid Machine Learning Model: Autoencoder and Generative Adversarial Networks
Authors: Cheng Meiling , Fang Fangxin , Navon Ionel M. , Zheng Jie , Tang Xiao , Zhu Jiang , Pain Christopher
Published: February 2022

Efficient and accurate real‐time forecasting of national spatial ozone distribution is critical to the provision of effective early warning. Traditional numerical air quality models require a high computational cost associated with running large‐scale numerical simulations. In this work, we introduce a hybrid model (VAE‐GAN) combining a generative adversarial network (GAN) with a variational autoencoder (VAE) to learn the dynamic ozone distributions in spatial and temporal spaces. The VAE‐GAN model can not only decipher the complex nonlinear relationship between the inputs (the past states/ozone and meteorological factors) and outputs (ozone), but also provide ozone forecasts for a long lead‐time beyond the training period. The performance of VAE‐GAN is demonstrated in hourly and daily spatio‐temporal ozone forecasts over China. The training datasets from 2013 to 2017 and validation datasets from 2018 to 2019 are the collection of data from the air quality reanalysis datasets. With the use of VAE, large dataset sizes are decreased by three orders of magnitude, enabling hourly and daily forecasts to be computed in seconds. Results show that the VAE‐GAN achieves a reasonable accuracy in the prediction of both the spatial and temporal evolution patterns of hourly and daily ozone fields, as compared to the Nested Air Quality Prediction Modeling System (commonly used in China), the reanalysis data and observations during the validation period. Thus, the VAE‐GAN is a cost‐effective tool for large data‐driven predictions, which can potentially reinforce air pollution prediction efforts in providing risk assessment and management in a timely manner.
Development of a Reservoir Flood Control Scheme for Global Flood Models
Authors: Hanazaki Risa , Yamazaki Dai , Yoshimura Kei
Published: February 2022

Integrating reservoir flood control operations in global flood forecasting systems is important for accurately estimating discharge and other variables. Because existing modeling operational rules and parameters do not reflect the actual variability due to a lack of associated data, globally applicable modeling of flood regulation needs to be studied further. In this study, we developed a flood control operation scheme with refined parameters and algorithms to tackle this problem. We used recently developed objective data sets of reservoir dynamics to more realistically estimate different reservoir parameters, such as flood storage capacity. Furthermore, the algorithm for the operational rule was modified by introducing a new release coefficient such that the peak attenuation depended on the reservoir's ability to regulate floods. The operation scheme for 2,169 dams was introduced into the CaMa‐Flood global hydrodynamic model. Compared to the simulation without reservoirs, the Nash‐Sutcliffe Efficiency and peak discharge error in the daily river discharge improved at 62.2% and 49.9% of the gauges, respectively, after the integration. Compared to the parameter estimated by a method in previous studies, the newly estimated flood storage capacity parameters reduced the peak discharge error at 47% of the gauges downstream of the reservoirs where the flood storage capacity ratio is small (≤50%). Furthermore, the modification of operational rules had the effect of mitigating people exposed to flooding by ∼10%. This study informs the integration and the refinements of the reservoir operation scheme to improve global flood simulation and forecasting.
TSPAN6 is a suppressor of Ras-driven cancer
Authors: Humbert Patrick O. , Pryjda Tamara Zoranovic , Pranjic Blanka , Farrell Andrew , Fujikura Kohei , de Matos Simoes Ricardo , Karim Rezaul , Kozieradzki Ivona , Cronin Shane J. F. , Neely G. Gregory , Meyer Thomas F. , Hagelkruys Astrid , Richardson Helena E. , Penninger Josef M.
Published: February 2022

Oncogenic mutations in the small GTPase RAS contribute to ~30% of human cancers. In aDrosophilagenetic screen, we identified novel and evolutionary conserved cancer genes that affect Ras-driven tumorigenesis and metastasis inDrosophilaincluding confirmation of the tetraspanin Tsp29Fb. However, it was not known whether the mammalian Tsp29Fb orthologue, TSPAN6, has any role in RAS-driven human epithelial tumors. Here we show that TSPAN6 suppressed tumor growth and metastatic dissemination of humanRASactivating mutant pancreatic cancer xenografts. Whole-body knockout as well as tumor cell autonomous inactivation using floxed alleles ofTspan6in mice enhancedKrasG12D-driven lung tumor initiation and malignant progression. Mechanistically, TSPAN6 binds to the EGFR and blocks EGFR-induced RAS activation. Moreover, we show that inactivation ofTSPAN6induces an epithelial-to-mesenchymal transition and inhibits cell migration in vitro and in vivo. Finally, lowTSPAN6expression correlates with poor prognosis of patients with lung and pancreatic cancers with mesenchymal morphology. Our results uncover TSPAN6 as a novel tumor suppressor receptor that controls epithelial cell identify and restrains RAS-driven epithelial cancer.
MicroRNAs serve as prediction and treatment-response biomarkers of attention-deficit/hyperactivity disorder and promote the differentiation of neuronal cells by repressing the apoptosis pathway
Authors: Wang Liang-Jen , Kuo Ho-Chang , Lee Sheng-Yu , Huang Lien-Hung , Lin Yuyu , Lin Pei-Hsien , Li Sung-Chou
Published: February 2022

Attention-deficit/hyperactivity disorder (ADHD) is a highly heritable neurodevelopmental disorder. This study aimed to examine whether miRNA expression abundance in total white blood cells (WBCs) facilitated the identification of ADHD and reflected its response to treatment. Furthermore, whether miRNA markers facilitated the growth of the human cortical neuronal (HCN-2) cells was also investigated. Total WBC samples were collected from 145 patients and 83 controls, followed by RNA extraction and qPCR assays. Subsequently, WBC samples were also collected at the endpoint from ADHD patients who had undergone 12 months of methylphenidate treatment. The determined ΔCt values of 12 miRNAs were applied to develop an ADHD prediction model and to estimate the correlation with treatment response. The prediction model applying the ΔCt values of 12 examined miRNAs (using machine learning algorithm) demonstrated good validity in discriminating ADHD patients from controls (sensitivity: 96%; specificity: 94.2%). Among the 92 ADHD patients completing the 12-month follow-up, miR-140-3p, miR-27a-3p, miR-486-5p, and miR-151-5p showed differential trends of ΔCt values between treatment responders and non-responders. In addition, the in vitro cell model revealed that miR-140-3p and miR-126-5p promoted the differentiation of HCN-2 cells by enhancing the length of neurons and the number of junctions. Microarray and flow cytometry assays confirmed that this promotion was achieved by repressing apoptosis and/or necrosis. The findings of this study suggest that the expression levels of miRNAs have the potential to serve as both diagnostic and therapeutic biomarkers for ADHD. The possible biological mechanisms of these biomarker miRNAs in ADHD pathophysiology were also clarified.
Quantitative multidimensional phenotypes improve genetic analysis of laterality traits
Authors: Schmitz Judith , Zheng Mo , Lui Kelvin F. H. , McBride Catherine , Ho Connie S.-H. , Paracchini Silvia
Published: February 2022

Handedness is the most commonly investigated lateralised phenotype and is usually measured as a binary left/right category. Its links with psychiatric and neurodevelopmental disorders prompted studies aimed at understanding the underlying genetics, while other measures and side preferences have been less studied. We investigated the heritability of hand, as well as foot, and eye preference by assessing parental effects (n ≤ 5028 family trios) and SNP-based heritability (SNP-h2,n ≤ 5931 children) in the Avon Longitudinal Study of Parents and Children (ALSPAC). An independent twin cohort from Hong Kong (n = 358) was used to replicate results from structural equation modelling (SEM). Parental left-side preference increased the chance of an individual to be left-sided for the same trait, with stronger maternal than paternal effects for footedness. By regressing out the effects of sex, age, and ancestry, we transformed laterality categories into quantitative measures. The SNP-h2for quantitative handedness and footedness was 0.21 and 0.23, respectively, which is higher than the SNP-h2reported in larger genetic studies using binary handedness measures. The heritability of the quantitative measure of handedness increased (0.45) compared to a binary measure for writing hand (0.27) in the Hong Kong twins. Genomic and behavioural SEM identified a shared genetic factor contributing to handedness, footedness, and eyedness, but no independent effects on individual phenotypes. Our analysis demonstrates how quantitative multidimensional laterality phenotypes are better suited to capture the underlying genetics than binary traits.
Evaluation of tumour surveillance protocols and outcomes in von Hippel-Lindau disease in a national health service
Authors: Maher Eamonn R. , Adlard Julian , Barwell Julian , Brady Angela F. , Brennan Paul , Cook Jackie , Crawford Gillian S. , Dabir Tabib , Davidson Rosemarie , Dyer Rebecca , Harrison Rachel , Forde Claire , Halliday Dorothy , Hanson Helen , Hay Eleanor , Higgs Jenny , Jones Mari , Lalloo Fiona , Miedzybrodzka Zosia , Ong Kai Ren , Pelz Frauke , Ruddy Deborah , Snape Katie , Whitworth James , Sandford Richard N.
Published: February 2022

Background

Von Hippel-Lindau (VHL) disease is an inherited tumour predisposition syndrome and a paradigm for the importance of early diagnosis and surveillance. However, there is limited information on the “real world” management of VHL disease.

Methods

A national audit of VHL disease in the United Kingdom.

Results

VHL disease was managed mostly via specialist clinics coordinated through regional clinical genetics services (but frequently involving additional specialties). Over the study period, 19 genetic centres saw 842 individuals (393 males, 449 females) with a clinical and/or molecular diagnosis of VHL disease and 74 individuals (35 male, 39 female) with a prior risk of 50% (affected parent). All centres offered retinal, central nervous system and abdominal surveillance to affected individuals and at-risk relatives though surveillance details differed between centres (but complied with international recommendations). Renal lesions detected on the first surveillance scan were, on average, larger than those detected during subsequent scans and the larger the diameter at detection the greater the likelihood of early intervention.

Conclusions

In a state-funded health care system individuals with a rare inherited cancer predisposition syndrome are generally able to access appropriate surveillance and patient management is improved compared to historical data. The “real world” data from this study will inform the future development of VHL management protocols.