bluuebunny/crossref_metadata_2025 huggingface dataset:
Untersuchung von Aufmerksamkeitseffekten für die gezielte Gestaltung von Visualisierungsoberflächen für zeitgemäße Mensch-Maschine-Interaktion
Authors: Hoppe Annette , Ganßauge Rico , Geißler Uwe , Henke Anna-Sophia , Reßut Norman
Published: January 2022

In der modernen Arbeitswelt besteht eine wachsende Bedeutung von Steuer- und Überwachungstätigkeiten, die heute in Leitwarten und in Zukunft möglicherweise mittels neuer Interaktionsformen ausgeführt werden. Bei diesen Tätigkeiten ist verantwortungsvolles Handeln gefordert, da eine Verpflichtung für die Aufrechterhaltung der Prozesse besteht. Die Mensch-Maschine-Interaktion findet häufig mittels einer komplexen Visualisierung sowie einer Vielzahl an Bildschirmen statt. Dies kann bedeuten, dass sich relevante Information außerhalb der direkten visuellen Wahrnehmung eines Bedieners befinden. Es besteht die Herausforderung, die Aufmerksamkeit durch Signale gezielt zu lenken, damit handlungsleitende Informationen wahrnehmbar werden. Ziel der durchgeführten Untersuchung war es deshalb, Mindestanforderungen für die Erkennung von Signalen im peripheren Blickfeld zu untersuchen. Ausgehend von Vorerkenntnissen wurden in einem Laborexperiment Signale in verschiedenen Leuchtdichtekontrasten und Frequenzen in festgelegten Winkeln des peripheren Blickfeldes untersucht. Diese zeigen die Überlegenheit hoher Leuchtdichtekontraste und Frequenzen für die Erkennung, steigende Winkel verringerten diese. Die aus den Daten abgeleiteten Regressionen gestatten die Abschätzung von Erkennungswahrscheinlichkeit und Reaktionszeiten.

Praktische Relevanz: Die erreichten Ergebnisse geben Entwickler*innen und Anwender*innen von Technik ein Werkzeug für die gezielte Gestaltung von Signalen in der Mensch-Maschine-Interaktion bei komplexen Visualisierungshintergründen an die Hand. Aus den Erkenntnissen können konkrete Maßnahmen abgeleitet werden, die helfen, Sicherheit und Zuverlässigkeit durch eine verbesserte Gestaltung der Mensch-Maschine-Interaktion zu unterstützen.
Maximizing Regulatory Review Efficiency: The Evolution of the FDA OCE RTOR Pilot
Authors: Gao Ya Grace , Roberts Samantha , Guy Allison
Published: January 2022

To promote the efficient review of oncology drug applications, the US Food and Drug Administration (FDA) Oncology Center of Excellence (OCE) launched the Real-Time Oncology Review (RTOR) pilot program in 2018. RTOR allows FDA to review individual sections of eCTD modules of a drug application for oncology drugs in contrast to requiring the applicant to submit complete modules or the complete application before review is initiated. Initially, the program accepted only supplemental applications with simple study designs and easily interpretable endpoints, but the scope has since been expanded to include applications for New Molecular Entities (NME), and other applications with more complex features. Though many applicants experience faster approvals under RTOR, it is difficult to isolate the effect of the RTOR program on review timelines as its contribution is masked by other expedited programs like priority review and breakthrough therapy designation (BTD). This article discusses the expanded scope of RTOR, its interplay with other OCE initiatives to modernize regulatory review, summarizes Genentech’s experiences in planning RTOR submissions from February 2019 to July 2021, and provides considerations for the future of the program.
Disagreement on expectations: firms versus consumers
Authors: Claveria Oscar
Published: January 2022

This paper evaluates the dynamic response of economic activity to shocks in agents’ perception of uncertainty. The study focuses on the comparison between manufacturers’ and consumers’ perception of economic uncertainty, gauged by a geometric discrepancy indicator to quantify the proportion of disagreement in eleven European countries and the Euro Area. A vector autoregressive framework is used to estimate the impulse response functions to innovations in disagreement, both for manufacturers and consumers. The effect on economic activity of shocks to the perception of uncertainty is found to differ markedly between both types of agents. On the one hand, shocks to consumer discrepancy tend to be of greater magnitude and duration than those to manufacturer discrepancy. On the other hand, innovations in disagreement between the two collectives have an opposite effect on economic activity: shocks to manufacturer discrepancy lead to a decrease in economic activity, as opposed to shocks to consumer discrepancy. This finding is of particular relevance to researchers when using cross-sectional dispersion of survey-based expectations for approximating and assessing economic uncertainty, since the effect on economic growth of shocks to disagreement may be dependent on the type of agent and the way in which expectations have been elicited.
„Lügenpresse“, „alternative Fakten“ und die epistemologische Naivität des sozialen Konstruktivismus
Authors: Kempf Wilhelm
Published: January 2022

Aufbauend auf dem methodischen Konstruktivismus und gestützt auf die Unterscheidung zwischen (1) einer transsubjektiv begründeten (objektiven) Wirklichkeit, einer bloß intersubjektiv geteilten (sozialen) Wirklichkeit und einer subjektiven Wirklichkeit i.e. S. sowie (2) zwischen (gesicherten) Tatsachen, möglichen Sachverhalten, fingierten Sachverhalten und simulierten Sachverhalten wird die Haltbarkeit der sozial-konstruktivistischen Auffassung untersucht, wonach jede Repräsentation der Wirklichkeit nur ein verzerrtes Abbild der Realität biete, weshalb alle Repräsentation der Wirklichkeit gleichrangig nebeneinanderstehen.

Dass die sozial konstruierte Wirklichkeit notgedrungen selektiv und daher eine interpretierte (bedeutungshaltige) Wirklichkeit ist, wird nicht in Frage gestellt, wohl jedoch die Schlussfolgerungen, welche der soziale Konstruktivismus daraus zieht: (1) Die Rede von einer „äußeren Realität“ und deren „Repräsentation“ kann nicht aufrechterhalten werden. (2) Im Unterschied zu Tatsachen, die transsubjektiv nachgeprüft werden können, entbehren Bedeutungen einer transsubjektiven Basis, weshalb Aussagen über die Bedeutung eines Sachverhalts weder wahr noch falsch sind. (3) Trotzdem kann nicht jede bedeutungshaltige Wirklichkeitskonstruktion denselben Geltungsanspruch erheben. (4) Zumindest „alternative Fakten“ sind als solche identifizierbar. (5) Wahrheit vs. Falschheit behaupteter Sachverhalte ist nicht das einzige Kriterium, an dem eine Wirklichkeitskonstruktion gemessen werden kann. (6) Obwohl der Diskurs über Bedeutungen kein Diskurs darüber sein kann, ob sie wahr oder falsch sind, können Wirklichkeitskonstruktionen dennoch auf ihre Angemessenheit hin befragt werden. Und je nachdem, worauf wir unser Handeln orientieren, können sie sich als angemessen oder unangemessen erweisen.
Microbial enhancement of plant nutrient acquisition
Authors: Singh Sunil K. , Wu Xiaoxuan , Shao Chuyang , Zhang Huiming
Published: January 2022

Nutrient availability is a determining factor for crop yield and quality. While fertilization is a major approach for improving plant nutrition, its efficacy can be limited and the production and application of fertilizers frequently bring problems to the environment. A large number of soil microbes are capable of enhancing plant nutrient acquisition and thereby offer environmentally benign solutions to meet the requirements of plant nutrition. Herein we provide summations of how beneficial microbes enhance plant acquisition of macronutrients and micronutrients. We also review recent studies on nutrition-dependent plant-microbe interactions, which highlight the plant’s initiative in establishing or deterring the plant-microbe association. By dissecting complex signaling interactions between microbes within the root microbiome, a greater understanding of microbe-enhanced plant nutrition under specific biotic and abiotic stresses will be possible.
The needs, challenges, and burden experienced by informal caregivers in Uganda: a scoping review
Authors: Komuhangi A. , Jenkins C. , Nakaggwa F. , Agaba P. , Githinji F. , Ewuzie A. , Apio J. , Namwanje A. Kawooya , Santin O. , MacDonald M. , McShane C. M. , Misinde C. , Montgomery L. , Nanyonga R. Clarke
Published: January 2022

Background

The impact of informal caregiving is increasingly recognised as an important but often particularly neglected area of research in low and middle income countries. It is important to understand not only the effect of care on patient outcomes, but also the impact of caring on caregivers’ health and wellbeing.

Methods

Guided by the Arksey and O’Malley (Res Methodol 8:19–32, 2005) framework, this scoping review sought to collate and chart existing research on the needs, burdens and challenges experienced by caregivers in Uganda.

Results

The results of this review indicate that research focusing on the needs of caregivers for individuals with communicable disease, particularly HIV, has been well developed in Uganda, however, there is a lack of research on caregiving related to non-communicable diseases. Research has been dominated by small qualitative studies that are informative for understanding roles, burdens and contextually-specific aspects of care, but there is a need for larger studies that develop and test interventions designed to support the needs of caregivers.

Conclusions

Recurrent themes identified within this review, such as challenges in providing physical support and accessing treatment services, financial costs of care, psychological and mental health impacts and the experience of stigma, should help to inform well targeted and contextually-appropriate future research and interventions.
Computational analysis and design of an aerofoil with morphing tail for improved aerodynamic performance in transonic regime
Authors: Rana Z.A. , Mauret F. , Sanchez-Gil J.M. , Zeng K. , Hou Z. , Dayyani I. , Könözsy L.
Published: January 2022

This article focuses on the aerodynamic design of a morphing aerofoil at cruise conditions using computational fluid dynamics (CFD). The morphing aerofoil has been analysed at a Mach number of 0.8 and Reynolds number of
$3 \times 10^{6}$
, which represents the transonic cruise speed of a commercial aircraft. In this research, the NACA0012 aerofoil has been identified as the baseline aerofoil where the analysis has been performed under steady conditions at a range of angles of attack between
$0^{^{\kern1pt\circ}}$
and
$3.86^{^{\kern1pt\circ}}$
. The performance of the baseline case has been compared to the morphing aerofoil for different morphing deflections (
$w_{te}/c = [0.005 - 0.1]$
) and start of the morphing locations (
$x_{s}/c = [0.65 - 0.80]$
). Further, the location of the shock wave on the upper surface has also been investigated due to concerns about the structural integrity of the morphing part of the aerofoil. Based upon this investigation, a most favourable morphed geometry has been presented that offers both, a significant increase in the lift-to-drag ratio against its un-morphed counterpart and has a shock location upstream of the start of the morphing part.
BPMN++ to support managing organisational, multiteam and systems engineering aspects in cyber physical production systems design and operation
Authors: Vogel-Heuser Birgit , Reif Julia A. M. , Passoth Jan-Hendrik , Huber Christoph , Brodbeck Felix C. , Maasen Sabine , Lindemann Udo , Hujo Dominik
Published: January 2022

Interdisciplinary engineering of cyber physical production systems (CPPS) are often subject to delay, cost overrun and quality problems or may even fail due to the lack of efficient information exchange between multiple interdisciplinary teams working in complex networks within and across companies. We propose a direct integration of multiteam and organisational aspects into the graphical notation of the systems engineering workflow. BPMN++, with eight new notational elements and two subdiagrams, enables the modelling of the required cooperation aspects. BPMN++ provides an improved overview, uniform notation, more compact presentation and easier modifiability from an engineering point of view. We also included a first set of empirical studies and historical qualitative and quantitative data in addition to subjective expert-based ratings to increase validity. The use case introduced to explain the procedure and the notation is derived from surveys in plant manufacturing focussing on the start-up phase and decision support at site. This, in particular, is one of the most complex and critical phases with potentially high economic impact. For evaluation purposes, we compare two alternative solutions for a short-term management decision in the start-up phase of CPPS using the BPMN++ approach.
Time-of-flight methodologies with large-area diamond detectors for ion characterization in laser-driven experiments
Authors: Salvadori M. , Di Giorgio G. , Cipriani M. , Scisciò M. , Verona C. , Andreoli P. L. , Cristofari G. , De Angelis R. , Pillon M. , Andreev N. E. , Antici P. , Borisenko N. G. , Giulietti D. , Migliorati M. , Rosmej O. , Zähter S. , Consoli F.
Published: January 2022

The time-of-flight technique coupled with semiconductor detectors is a powerful instrument to provide real-time characterization of ions accelerated because of laser–matter interactions. Nevertheless, the presence of strong electromagnetic pulses (EMPs) generated during the interactions can severely hinder its employment. For this reason, the diagnostic system must be designed to have high EMP shielding. Here we present a new advanced prototype of detector, developed at ENEA-Centro Ricerche Frascati (Italy), with a large-area (15 mm × 15 mm) polycrystalline diamond sensor having 150 μm thickness. The tailored detector design and testing ensure high sensitivity and, thanks to the fast temporal response, high-energy resolution of the reconstructed ion spectrum. The detector was offline calibrated and then successfully tested during an experimental campaign carried out at the PHELIX laser facility (

${E}_L\sim$

100 J,

${\tau}_L = 750$

fs,

${I}_L\sim \left(1{-}2.5\right)\times {10}^{19}$

W/cm2) at GSI (Germany). The high rejection to EMP fields was demonstrated and suitable calibrated spectra of the accelerated protons were obtained.
Cladding-pumped Raman fiber laser with 0.78% quantum defect enabled by phosphorus-doped fiber
Authors: Ma Xiaoya , Xu Jiangming , Ye Jun , Zhang Yang , Huang Liangjin , Yao Tianfu , Leng Jinyong , Pan Zhiyong , Zhou Pu
Published: January 2022

The quantum defect (QD) is an important issue that demands prompt attention in high-power fiber lasers. A large QD may aggravate the thermal load in the laser, which would impact the frequency, amplitude noise and mode stability, and threaten the security of the high-power laser system. Here, we propose and demonstrate a cladding-pumped Raman fiber laser (RFL) with QD of less than 1%. Using the Raman gain of the boson peak in a phosphorus-doped fiber to enable the cladding pump, the QD is reduced to as low as 0.78% with a 23.7 W output power. To our knowledge, this is the lowest QD ever reported in a cladding-pumped RFL. Furthermore, the output power can be scaled to 47.7 W with a QD of 1.29%. This work not only offers a preliminary platform for the realization of high-power low-QD fiber lasers, but also proves the great potential of low-QD fiber lasers in power scaling.
Characterization of coupling between inertial particles and turbulent wakes from porous disk generators
Authors: Travis Kristin N. , Smith Sarah E. , Vignal Laure , Djeridi Henda , Bourgoin Mickaël , Cal Raúl Bayoán , Obligado Martín
Published: January 2022

This study presents the findings of a wind tunnel experiment investigating the behaviour of micrometric inertial particles with Stokes numbers around unity in the turbulent wake of a stationary porous disk. Various concentrations

$\varPhi _{v}\in ([6-19] \times 10^{-6})$

of poly-disperse water droplets (average diameter 40–50 

$\mathrm {\mu }$

m) are compared with sub-inertial tracer particles. Hot-wire anemometry, phase Doppler interferometry and particle image velocimetry were implemented in the near- and far-wake regions to study the complex dynamics of such particles. Quadrant analysis is used to explore the shear effects of the particle wake interaction. Turbulence statistics and particle size distributions reveal distinct differences in the structure of the wake when inertial particles are present in the flow. Additionally, there are different structures in the near and far wake regions and structures change with particle volume fraction.
Mapping the invisible: knowledge, credibility and visions of earth in early modern cave maps
Authors: Mattes Johannes
Published: January 2022

This paper examines cave environments as unique spaces of knowledge production and shows how visualizations of natural cavities in maps came to be powerful tools in scientific reasoning. Faced with the challenge of limited vision, mapmakers combined empiricism and imagination in an experimental setting and developed specific translation strategies to deal with the uncertain origin of underground objects and the shifting boundaries between the known and the unknown. By deconstructing this type of cartographic representation, which has barely been studied, this paper furnishes surprising insights into the scholarly practices and tools used to deal with this considerable epistemic uncertainty and to signal credibility and trust to potential users. The array of maps used for this study includes both archival and published sources, depicting caves in Europe, America and Siberia.
Identification and pathogenicity ofPratylenchus scribnerion tomato in Sichuan Province of People's Republic of China
Authors: Xia Y.H. , Li J. , Sun M.R. , Lei B. , Li H.L. , Li Y. , Wang K.
Published: January 2022

Root-lesion nematodes (Pratylenchusspp.) are a group of economically important pathogens that have caused serious economic losses in many crops. In 2019, root-lesion nematodes were recovered from tomato (Solanum lycopersicum) root samples collected from Sichuan Province, People's Republic of China (PRC). Extracted nematodes were disinfected, and one individual female was cultured on a carrot disc for propagation at 25 °C by parthenogenesis and designated the SC isolate. Afterwards, the isolate was identified on the basis of morphometric and molecular markers. Both morphometric characters and molecular analysis of the internal transcribed spacer region gene (ITS) of ribosomal DNA, the D2-D3 expansion region of the 28S rDNA gene and the mitochondrial cytochrome oxidase I (mtDNA-COI) gene revealed that the species of root-lesion nematode wasPratylenchus scribneri. The Bayesian tree inferred from the ITS rDNA, 28S rDNA and mtDNA-COI gene sequences also showed that this isolate formed a highly supported clade with otherP. scribneriisolates. The pathogenicity of the root-lesion nematode SC isolate on tomato was assessed, showing that tomato was a suitable host forP. scribneri. To the best of our knowledge, this is the first report ofP. scribnerion tomato in Sichuan Province, PRC. These are also the first molecular data obtained fromP. scribnerion tomato in the PRC, and the pathogenicity ofP. scribnerito tomato was studied for the first time. This study provides scientific data for the detection, identification and control of tomato root-lesion nematode disease.
Middle-ear effusion in children with cleft palate: congenital or acquired?
Authors: Kraus F , Hagen R , Shehata-Dieler W
Published: January 2022

Objective

Cleft palates are one of the most common congenital malformations. Because of the loss of Eustachian tube function, middle-ear ventilation is reduced. The aim of this study was to determine if middle-ear effusions were present at birth or at the three-month audiological evaluation.

Method

A total of 53 children with a cleft palate were included. Data review included the results of newborn hearing screening, microscopic findings, a tympanometry, a free field audiometry and intra-operative findings.

Results

A total of 58.4 per cent of patients had a median, 26.4 per cent had a bilateral, 11.3 per cent had a unilateral and 3.8 per cent had a limited soft palate cleft. Newborn hearing screening showed a pass in 83.1 per cent of newborns bilaterally. The first ear microscopy showed a bilateral middle-ear effusion in 90.6 per cent of cases. During cleft surgery, bilateral paracentesis was performed in all cases, and in 90.6 per cent middle-ear effusion was sucked out.

Conclusion

The majority of children with a cleft palate do not present with middle-ear effusion at birth. It develops within several days or weeks of life.
The J. Derek Bewley Career Lecture. Seeds–plants–crops–biodiversity–environment–people: illustrating understanding and ideas
Authors: Ellis Richard H.
Published: January 2022

The J. Derek Bewley Career Lectures presented at the triennial meetings of the International Society of Seed Science support early-career seed scientists by providing retrospective views, from those late in their careers, of lessons learned and future implications. Ambition, ability, inspiration, foresight, hard work and opportunity are obvious career requirements. The importance of mentoring and teamwork combined with the clear communication of results, understanding and ideas are emphasized. The role of illustration in research, and its dissemination, is outlined: illustration can support hypothesis development, testing and communication. Climate change may perturb the production of high-quality seed affecting conservation as well as agriculture, horticulture and forestry. An illustrative synthesis of the current understanding of temporal aspects of the effects of seed production environment on seed quality (assessed by subsequent seed storage longevity) is provided for wheat (Triticum aestivum L.) and rice (Oryza sativa L.). Seed science research can contribute to complex global challenges such as future food supplies from seed-propagated crops in our changing climate whilst conserving biological diversity (through seed ecology and technologies such as ex situ plant genetic resources conservation by long-term seed storage in genebanks), but only if that research can be – and then is – applied.
Prenatal diagnosis lowers neonatal cardiac care costs in resource-limited settings
Authors: Vaidyanathan Balu , Rani Karthika , Kunde Farooq , Thomas Stephy , Sudhakar Abish , Kumar Raman Krishna , Zheleva Bistra
Published: January 2022

Background:

Prenatal diagnosis of critical CHDs and planned peripartum care is an emerging concept in resource-limited settings.

Objective:

To report the impact of prenatal diagnosis and planned peripartum care on costs of neonatal cardiac care in a resource-limited setting.

Methods:

Prospective study (October 2019 to October 2020). Consecutive neonates undergoing surgery or catheter-based interventions included. Patients were divided into prenatal (prenatal diagnosis) and post-natal (diagnosis after birth) groups. Costs of cardiac care (total, direct, and indirect) and health expenses to income ratio were compared between study groups; factors impacting costs were analysed.

Results:

A total of 105 neonates were included, including 33 in prenatal group. Seventy-seven neonates (73.3%) underwent surgical procedures while the rest needed catheter-based interventions. Total costs were 16.2% lower in the prenatal group (p = 0.008). Direct costs were significantly lower in the prenatal group (18%; p = 0.02), especially in neonates undergoing surgery (20.4% lower; p = 0.001). Health expenses to income ratio was also significantly lower in the prenatal group (2.04 (1.03–2.66) versus post-natal:2.58 (1.55–5.63), p = 0.01);, particularly in patients undergoing surgery (prenatal: 1.58 (1.03–2.66) vs. post-natal: 2.99 (1.91–6.02); p = 0.002). Prenatal diagnosis emerged as the only modifiable factor impacting costs on multivariate analysis.

Conclusion:

Prenatal diagnosis and planned peripartum care of critical CHD is feasible in resource-limited settings and is associated with significantly lower costs of neonatal cardiac care. The dual benefit of improved clinical outcomes and lower costs of cardiac care should encourage policymakers in resource-limited settings towards developing more prenatal cardiac services.
Fractal Behaviors of Hydraulic Head and Surface Runoff of the Nested Groundwater Flow Systems in Response to Rainfall Fluctuations
Authors: Zhang Xiaolang , Li Hailong , Jiao Jiu Jimmy , Luo Xin , Kuang Xingxing , Mao Rong , Hu Wenli
Published: January 2022

The responses of the nested groundwater flow systems (NGFS) to rainfall fluctuations and the impacts of the NGFS on surface runoff are explored using a fully coupled variably saturated groundwater‐surface water model in conjunction with spectral analysis. Numerical experiments are designed to investigate the fractal behaviors of hydraulic head and surface runoff in different scenarios. The results show that the inlets, outlets, and flow patterns of the sub‐systems of NGFS can change with rainfall. The scaling‐exponent, defined as the slope of the power spectra of the fluctuations of hydraulic head or runoff, is used to depict the fractal behaviors. The scaling‐exponent of the hydraulic head is highly variable within the unsaturated zone and local flow systems but remains constant within the intermediate and regional systems. Whether the scaling‐exponent of surface runoff exhibits a linear relation with the watershed size depends on the proportion of baseflow in the runoff.
Implications of Sound Velocities of Natural Topaz on the Seismic L‐Discontinuity
Authors: Chen Sibo , Cai Nao , Wang Siheng , Qi Xintong , Li Baosheng
Published: January 2022

Compressional and shear wave velocities of topaz have been measured by ultrasonic interferometry in a multi‐anvil apparatus up to 13 GPa at room temperature. By fitting the measured velocities under pressure to finite strain equations, the elastic moduli of topaz and their pressure derivatives were obtained, yielding KS0 = 165.5 (25) GPa, KS′ = 2.9 (1), G0 = 116.5 (17) GPa, and G′ = 1.0 (1). Modeling of the velocity profiles of subducted sediments suggests that at 8 GPa (∼240 km depth) the P‐ and S‐ wave velocities of the subducted sediments exhibit a first order increase of 10% and 11%, respectively. The comparison between seismic observations and velocity contrasts of sediment + MORB model at 240 km shows dehydration of a 1.5–3.9 km thick sediment layer can potentially contribute to the seismically observed Lehmann discontinuity in Tonga, Japan, Philippine Sea, South America, Indonesia, and South Shetland subduction zones.
Three‐Dimensional Variation of the Slab Geometry Within the South American Subduction System
Authors: Liu Meng , Gao Haiying
Published: January 2022

Subduction of the Nazca plate results in the uneven distributions of earthquakes and arc volcanoes along the South America's western margin. Here, we construct a high‐resolution shear‐wave velocity model from immediately offshore to the backarc in South America, using advanced full‐wave ambient noise tomography. Our new model confirms and provides further constraints on three major features, including (a) extensive low‐velocity anomalies within the continental crust, (b) two high‐velocity flat slab segments located beneath southern Peru and central Chile, and (c) complex slab geometry at flat‐to‐normal transitional subduction. The flat slab segments roughly correlate with the volcanic gaps but not with the seismicity gaps. We suggest that variations of slab geometry along strike and down dip have significantly modified the flow patterns within the mantle wedge. Subduction of oceanic ridges has altered the slab dehydration processes, which can influence the distribution of arc volcanism and the occurrence of intermediate‐depth earthquakes.
Improving the Estimate of Summer Daytime Planetary Boundary Layer Height Over Land From GPS Radio Occultation Data
Authors: Wang Yinjun , Zeng Xubin , Xu Xiangde , Xie Feiqin , Zhao Yang
Published: January 2022

Global Positioning System (GPS) radio occultation measurements have been widely used to estimate global planetary boundary layer heights (H) using the minimum refractivity gradient method. This method is directly tested here using radiosonde data in China and is found to overestimate summer daytime H over land primarily in the presence of multi‐inversions in the lower troposphere. This deficiency is largely reduced by adding a constraint with lifting condensation level (LCL) in the derivation of H, particularly for LCL < 2 km (usually over humid regions). The primary reason is that our new method effectively avoids estimating H near the strong inversion corresponding to the minimum refractivity gradient in the free atmosphere. Applying our new method to the GPS radio occultation data, with LCL derived from surface automatic weather stations, yields more reasonable daytime variation and spatial distribution of H over land in China as compared to the ERA5 reanalysis and radiosonde data.
A Snapshot of New Zealand's Dynamic Deformation Field From Envisat InSAR and GNSS Observations Between 2003 and 2011
Authors: Hamling Ian J. , Wright Tim J. , Hreinsdóttir Sigrun , Wallace Laura M.
Published: January 2022

Measuring the deformation at the Earth's surface over a range of spatial and temporal scales is vital for understanding seismic hazard, detecting volcanic unrest, and assessing the effects of vertical land movements (VLMs) on sea level rise. Here, we combine ∼10 years of Interferometric Synthetic Aperture Radar (InSAR) observations from Envisat with interseismic campaign and continuous GNSS velocities to build a high‐resolution velocity field of New Zealand. Exploiting the horizontal GNSS observations, we estimate the vertical component of the deformation to provide the VLM for the entire 15,000‐km‐long coastline. The estimated vertical rates show large variability around the country as a result of volcanic, tectonic, and anthropogenic sources. Interseismic subsidence is observed in Kaikoura region supporting models of at least partial locking of the southern Hikurangi subduction interface. Despite data challenges in the mountainous regions from landslides, sediment compaction, and glaciers, InSAR data shows localized uplift of the Southern Alps.
Nanophotonics shines light on hyperbolic metamaterials
Authors: Aigner Andreas , Dawes Judith M. , Maier Stefan A. , Ren Haoran
Published: January 2022

Hyperbolic metamaterials with a unique hyperbolic dispersion relation allow propagating waves with infinitely large wavevectors and a high density of states. Researchers from Korea and Singapore provide a comprehensive review of hyperbolic metamaterials, including artificially structured hyperbolic media and natural hyperbolic materials. They explain key nanophotonic concepts and describe a range of applications for these versatile materials.
Time course of serum uric acid accumulation and the risk of diabetes mellitus
Authors: Tian Xue , Wang Anxin , Zuo Yingting , Chen Shuohua , Zhang Licheng , Zhao Yuhan , Liu Lulu , Wu Shouling , Luo Yanxia , Gao Jingli
Published: January 2022

Background

The impact of long-term serum uric acid (SUA) exposure and time course of SUA accumulation on diabetes mellitus (DM) is unknown. This study aimed to evaluate the association of cumulative SUA (cumSUA) exposure and its accumulation time course with risk of DM.

Methods

This prospective study included 46,434 participants without DM and underwent three examinations at 2006, 2008, and 2010. CumSUA from 2006 to 2010 was calculated, multiplying mean values between consecutive examinations by time intervals between visits. Time course of SUA accumulation was categorized as the slope of SUA versus time from 2006 to 2010, or by splitting the overall accumulation into an early (cumSUA06-08) and late accumulation (cumSUA08-10).

Results

During 6.99 years of follow-up, we identified 2971 incident DM cases. In the fully adjusted model, a higher risk of DM was observed in participants with the highest quartile of cumSUA (hazard ratio [HR], 1.31; 95% confidence interval [CI], 1.17–1.46), cumulative burden >0 (HR, 1.23; 95% CI, 1.08–1.40), and with 6 year of hyperuricemia exposure duration (HR, 1.25; 95% CI, 1.01–1.55). When considering the time course of SUA accumulation, participants with a negative slope (HR, 1.05; 95% CI, 1.01–1.12), or combined with cumSUA ≥ median and a negative slope had elevated risk of DM (HR, 1.58; 95% CI, 1.18–2.11).

Conclusions

Incident DM risk depends on cumulative exposure of SUA and time course of SUA accumulation. Early SUA accumulation resulted in a greater risk increase compared with later accumulation, emphasizing the importance of optimal SUA control early in life.
Early spectral EEG in preterm infants correlates with neurocognitive outcomes in late childhood
Authors: Nordvik Tone , Schumacher Eva M. , Larsson Pål G. , Pripp Are H. , Løhaugen Gro C. , Stiris Tom
Published: January 2022

Background

Evidence regarding the predictive value of early amplitude-integrated electroencephalography (aEEG)/EEG on neurodevelopmental outcomes at school age and beyond is lacking. We  aimed to investigate whether there is an association between early postnatal EEG and neurocognitive outcomes in late childhood.

Methods

This study is an observational prospective cohort study of premature infants with a gestational age <28 weeks. The total absolute band powers (tABP) of the delta, theta, alpha, and beta bands were analyzed from EEG recordings during the first three days of life. At 10–12 years of age, neurocognitive outcomes were assessed using the Wechsler Intelligence Scale for Children 4th edition (WISC-IV), Vineland adaptive behavior scales 2nd edition, and Behavior Rating Inventory of Executive Function (BRIEF). The mean differences in tABP were assessed for individuals with normal versus unfavorable neurocognitive scores.

Results

Twenty-two infants were included. tABP values in all four frequency bands were significantly lower in infants with unfavorable results in the main composite scores (full intelligence quotient, adaptive behavior composite score, and global executive composite score) on all three tests (p < 0.05).

Conclusions

Early postnatal EEG has the potential to assist in predicting cognitive outcomes at 10–12 years of age in extremely premature infants <28 weeks’ gestation.

Impact

Evidence regarding the value of early postnatal EEG in long-term prognostication in preterm infants is limited.

Our study suggests that early EEG spectral analysis correlates with neurocognitive outcomes in late childhood in extremely preterm infants.

Early identification of infants at-risk of later impairment is important to initiate early and targeted follow-up and intervention.
Enhanced long-term potentiation and impaired learning in mice lacking alternative exon 33 of CaV1.2 calcium channel
Authors: Navakkode Sheeja , Zhai Jing , Wong Yuk Peng , Li Guang , Soong Tuck Wah
Published: January 2022

The CACNA1C (calcium voltage-gated channel subunit alpha 1 C) gene that encodes the CaV1.2 channel is a prominent risk gene for neuropsychiatric and neurodegenerative disorders with cognitive and social impairments like schizophrenia, bipolar disorders, depression and autistic spectrum disorders (ASD). We have shown previously that mice with exon 33 deleted from CaV1.2 channel (CaV1.2-exon 33−/−) displayed increased CaV1.2 current density and single channel open probability in cardiomyocytes, and were prone to develop arrhythmia. As Ca2+ entry through CaV1.2 channels activates gene transcription in response to synaptic activity, we were intrigued to explore the possible role of Cav1.2Δ33 channels in synaptic plasticity and behaviour. Homozygous deletion of alternative exon 33 resulted in enhanced long-term potentiation (LTP), and lack of long- term depression (LTD), which did not correlate with enhanced learning. Exon 33 deletion also led to a decrease in social dominance, sociability and social novelty. Our findings shed light on the effect of gain-of-function of CaV1.2Δ33 signalling on synaptic plasticity and behaviour and provides evidence for a link between CaV1.2 and distinct cognitive and social behaviours associated with phenotypic features of psychiatric disorders like schizophrenia, bipolar disorder and ASD.
A pilot exploration of multi-omics research of gut microbiome in major depressive disorders
Authors: Zhao Haoyang , Jin Kangyu , Jiang Chaonan , Pan Fen , Wu Jing , Luan Honglin , Zhao Zhiyong , Chen Jingkai , Mou Tingting , Wang Zheng , Lu Jing , Lu Shaojia , Hu Shaohua , Xu Yi , Huang Manli
Published: January 2022

The pathophysiology of major depressive disorder (MDD) remains obscure. Recently, the microbiota-gut-brain (MGB) axis’s role in MDD has an increasing attention. However, the specific mechanism of the multi-level effects of gut microbiota on host metabolism, immunity, and brain structure is unclear. Multi-omics approaches based on the analysis of different body fluids and tissues using a variety of analytical platforms have the potential to provide a deeper understanding of MGB axis disorders. Therefore, the data of metagenomics, metabolomic, inflammatory factors, and MRI scanning are collected from the two groups including 24 drug-naïve MDD patients and 26 healthy controls (HCs). Then, the correlation analysis is performed in all omics. The results confirmed that there are many markedly altered differences, such as elevated Actinobacteria abundance, plasma IL-1β concentration, lipid, vitamin, and carbohydrate metabolism disorder, and diminished grey matter volume (GMV) of inferior frontal gyrus (IFG) in the MDD patients. Notably, three kinds of discriminative bacteria, Ruminococcus bromii, Lactococcus chungangensis, and Streptococcus gallolyticus have an extensive correlation with metabolome, immunology, GMV, and clinical symptoms. All three microbiota are closely related to IL-1β and lipids (as an example, phosphoethanolamine (PEA)). Besides, Lactococcus chungangensis is negatively related to the GMV of left IFG. Overall, this study demonstrate that the effects of gut microbiome exert in MDD is multifactorial.
Mechanistic/mammalian target of rapamycin and side effects of antipsychotics: insights into mechanisms and implications for therapy
Authors: Zhuo Chuanjun , Xu Yong , Hou Weihong , Chen Jiayue , Li Qianchen , Liu Zhidong , Dou Guangqian , Sun Yun , Li Ranli , Ma Xiaoyan , Tian Hongjun , Zhou Chunhua
Published: January 2022

Antipsychotic pharmacotherapy has been widely recommended as the standard of care for the treatment of acute schizophrenia and psychotic symptoms of other psychiatric disorders. However, there are growing concerns regarding antipsychotic-induced side effects, including weight gain, metabolic syndrome (MetS), and extrapyramidal motor disorders, which not only decrease patient compliance, but also predispose to diabetes and cardiovascular diseases. To date, most studies and reviews on the mechanisms of antipsychotic-induced metabolic side effects have focused on central nervous system mediation of appetite and food intake. However, disturbance in glucose and lipid metabolism, and hepatic steatosis induced by antipsychotic drugs might precede weight gain and MetS. Recent studies have demonstrated that the mechanistic/mammalian target of rapamycin (mTOR) pathway plays a critical regulatory role in the pathophysiology of antipsychotic drug-induced disorders of hepatic glucose and lipid metabolism. Furthermore, antipsychotic drugs promote striatal mTOR pathway activation that contributes to extrapyramidal motor side effects. Although recent findings have advanced the understanding of the role of the mTOR pathway in antipsychotic-induced side effects, few reviews have been conducted on this emerging topic. In this review, we synthesize key findings by focusing on the roles of the hepatic and striatal mTOR pathways in the pathogenesis of metabolic and extrapyramidal side effects, respectively. We further discuss the potential therapeutic benefits of normalizing excessive mTOR pathway activation with mTOR specific inhibitors. A deeper understanding of pathogenesis may inform future intervention strategies using the pharmacological or genetic inhibitors of mTOR to prevent and manage antipsychotic-induced side effects.
Senescence as a dictator of patient outcomes and therapeutic efficacies in human gastric cancer
Authors: Zhou Lulin , Niu Zubiao , Wang Yuqi , Zheng You , Zhu Yichao , Wang Chenxi , Gao Xiaoyan , Gao Lihua , Zhang Wen , Zhang Kaitai , Melino Gerry , Huang Hongyan , Wang Xiaoning , Sun Qiang
Published: January 2022

Senescence is believed to be a pivotal player in the onset and progression of tumors as well as cancer therapy. However, the guiding roles of senescence in clinical outcomes and therapy selection for patients with cancer remain obscure, largely due to the absence of a feasible senescence signature. Here, by integrative analysis of single cell and bulk transcriptome data from multiple datasets of gastric cancer patients, we uncovered senescence as a veiled tumor feature characterized by senescence gene signature enriched, unexpectedly, in the noncancerous cells, and further identified two distinct senescence-associated subtypes based on the unsupervised clustering. Patients with the senescence subtype had higher tumor mutation loads and better prognosis as compared with the aggressive subtype. By the machine learning, we constructed a scoring system termed as senescore based on six signature genes: ADH1B, IL1A, SERPINE1, SPARC, EZH2, and TNFAIP2. Higher senescore demonstrated robustly predictive capability for longer overall and recurrence-free survival in 2290 gastric cancer samples, which was independently validated by the multiplex staining analysis of gastric cancer samples on the tissue microarray. Remarkably, the senescore signature served as a reliable predictor of chemotherapeutic and immunotherapeutic efficacies, with high-senescore patients benefited from immunotherapy, while low-senescore patients were responsive to chemotherapy. Collectively, we report senescence as a heretofore unrecognized hallmark of gastric cancer that impacts patient outcomes and therapeutic efficacy.
Exosomes from adipose-derived mesenchymal stem cells alleviate sepsis-induced lung injury in mice by inhibiting the secretion of IL-27 in macrophages
Authors: Wang Xiaoyan , Liu Danyong , Zhang XiHe , Yang LiuMing , Xia Zhengyuan , Zhang Quanfu
Published: January 2022

Acute lung injury (ALI) represents a frequent sepsis-induced inflammatory disorder. Mesenchymal stromal cells (MSCs) elicit anti-inflammatory effects in sepsis. This study investigated the mechanism of exosomes from adipose-derived MSCs (ADMSCs) in sepsis-induced ALI. The IL-27r−/− (WSX-1 knockout) or wild-type mouse model of sepsis was established by cecal ligation and puncture (CLP). The model mice and lipopolysaccharide (LPS)-induced macrophages were treated with ADMSC-exosomes. The content of Dil-labeled exosomes in pulmonary macrophages, macrophages CD68+ F4/80+ in whole lung tissues, and IL-27 content in macrophages were detected. The mRNA expression and protein level of IL27 subunits P28 and EBI3 in lung tissue and the levels of IL-6, TNF-α, and IL-1β were measured. The pulmonary edema, tissue injury, and pulmonary vascular leakage were measured. In vitro, macrophages internalized ADMSC-exosomes, and ADMSC-exosomes inhibited IL-27 secretion in LPS-induced macrophages. In vivo, IL-27 knockout attenuated CLP-induced ALI. ADMSC-exosomes suppressed macrophage aggregation in lung tissues and inhibited IL-27 secretion. ADMSC-exosomes decreased the contents of IL-6, TNF-α, and IL-1β, reduced pulmonary edema and pulmonary vascular leakage, and improved the survival rate of mice. Injection of recombinant IL-27 reversed the protective effect of ADMSC-exosomes on sepsis mice. Collectively, ADMSC-exosomes inhibited IL-27 secretion in macrophages and alleviated sepsis-induced ALI in mice.
Microfluidic deep mutational scanning of the human executioner caspases reveals differences in structure and regulation
Authors: Roychowdhury Hridindu , Romero Philip A.
Published: January 2022

The human caspase family comprises 12 cysteine proteases that are centrally involved in cell death and inflammation responses. The members of this family have conserved sequences and structures, highly similar enzymatic activities and substrate preferences, and overlapping physiological roles. In this paper, we present a deep mutational scan of the executioner caspases CASP3 and CASP7 to dissect differences in their structure, function, and regulation. Our approach leverages high-throughput microfluidic screening to analyze hundreds of thousands of caspase variants in tightly controlled in vitro reactions. The resulting data provides a large-scale and unbiased view of the impact of amino acid substitutions on the proteolytic activity of CASP3 and CASP7. We use this data to pinpoint key functional differences between CASP3 and CASP7, including a secondary internal cleavage site, CASP7 Q196 that is not present in CASP3. Our results will open avenues for inquiry in caspase function and regulation that could potentially inform the development of future caspase-specific therapeutics.
Canagliflozin protects against cisplatin-induced acute kidney injury by AMPK-mediated autophagy in renal proximal tubular cells
Authors: Park Cheol Ho , Lee Bin , Han Myeonggil , Rhee Woo Joong , Kwak Man Sup , Yoo Tae-Hyun , Shin Jeon-Soo
Published: January 2022

Sodium-glucose cotransporter 2 inhibitors, which are recently introduced as glucose-lowering agents, improve cardiovascular and renal outcomes in patients with diabetes mellitus. These drugs also have beneficial effects in various kidney disease models. However, the effect of SGLT2 inhibitors on cisplatin-induced acute kidney injury (AKI) and their mechanism of action need to be elucidated. In this study, we investigated whether canagliflozin protects against cisplatin-induced AKI, depending on adenosine monophosphate-activated protein kinase (AMPK) activation and following induction of autophagy. In the experiments using the HK-2 cell line, cell viability assay and molecular analysis revealed that canagliflozin protected renal proximal tubular cells from cisplatin, whereas addition of chloroquine or compound C abolished the protective effect of canagliflozin. In the mouse model of cisplatin-induced AKI, canagliflozin protected mice from cisplatin-induced AKI. However, treatment with chloroquine or compound C in addition to administration of cisplatin and canagliflozin eliminated the protective effect of canagliflozin. Collectively, these findings indicate that canagliflozin protects against cisplatin-induced AKI by activating AMPK and autophagy in renal proximal tubular cells.
Establishment of gastric signet ring cell carcinoma organoid for the therapeutic drug testing
Authors: Li Guoliang , Ma Shuai , Wu Quanyou , Kong Defeng , Yang Zhenrong , Gu Zhaoru , Feng Lin , Zhang Kaitai , Cheng Shujun , Tian Yantao , Zhang Wen
Published: January 2022

Signet ring cell carcinoma (SRCC) has specific oncogenesis and phenotypic and treatment resistance heterogeneity. Systemic therapies are often ineffective, and predictive biomarkers to guide treatment are urgently needed. Tumor organoids have recently emerged as an ideal model for drug testing and screening. Here, we report gastric organoids established from tumor tissues comprising four SRCCs and eight non-SRCCs. Tumor organoids demonstrated different growth characteristics and morphologies. Changes in the original tumor genome were maintained during long-term culture from whole-exome sequencing (WES) analysis. Immunohistochemistry and H&E staining showed that the tissue characteristics of the primary tumor could be recapitulated. In addition, organoid lines successfully formed tumors in immunodeficient mice and maintained tumorigenic character. Different responses to 5-fluorouracil, oxaliplatin, docetaxel and irinotecan treatment were observed in SRCC and non-SRCC organoids. These results demonstrate that gastric organoid drug models, including SRCC, were highly similar to the original tumors in phenotypic and genotypic profiling and could be as living biomarkers for drug response testing.