bluuebunny/crossref_metadata_2025 huggingface dataset:
Was bewegt Lehrpersonen während der Schulschließungen? – Eine Analyse der Kommunikation im Twitter-Lehrerzimmer über Chancen und Herausforderungen digitalen Unterrichts
Authors: Fütterer Tim , Hoch Emely , Stürmer Kathleen , Lachner Andreas , Fischer Christian , Scheiter Katharina
Published: April 2021

Während der durch die Corona-Pandemie bedingten Schulschließungen im März 2020 führten viele Schulen Fernunterricht ein, der häufig ohne wirkliche Vorbereitung als digitaler Unterricht organisiert wurde. Daraufhin war ein verstärkter Austausch unter Lehrpersonen in Online-Communities zu erwarten. Eine Analyse der Kommunikation der Online-Community Twitter-Lehrerzimmer erlaubte Einblick in aktuelle Themen und ermöglichte zudem den Vergleich von Themen vor und während der Schulschließungen. Zur Identifikation von Themen wurden computerlinguistische Analysemethoden basierend auf 128.422 Tweets sowie eine qualitative Inhaltsanalyse von 270 Tweets durchgeführt. Es zeigte sich, dass Themen wie (a)synchroner digitaler Unterricht bereits vorher besprochen, während der Schulschließungen jedoch häufiger und breiter thematisiert wurden. Das Twitter-Lehrerzimmer wurde für gegenseitige Unterstützung sowie den Austausch über drängende Herausforderungen genutzt wie etwa die Verfügbarkeit geeigneter (datenschutzkonformer) Software. Die Ergebnisse legen somit Defizite des Digitalisierungsprozesses aus der Perspektive Twitter-affiner Lehrpersonen in Deutschland offen und zeigen das Potenzial von Online-Communities für Austausch und Vernetzung.
Dye-Sensitized Solar Cell for Indoor Applications: A Mini-Review
Authors: Devadiga Dheeraj , Selvakumar M. , Shetty Prakasha , Santosh M. S.
Published: April 2021

Lightweight computing technologies such as the Internet of Things and flexible wearable systems have penetrated our everyday lives exponentially in recent years. Without a question, the running of such electronic devices is a major energy problem. Generally, these devices need power within the range of microwatts and operate mostly indoors. Thus, it is appropriate to have a self-sustainable power source, such as the photovoltaic (PV) cell, which can harvest indoor light. Among other PV cells, the dye-sensitized solar cell (DSSC) has immense capacity to satisfy the energy demands of most indoor electronics, making it a very attractive power candidates because of its many benefits such as readily available materials, relatively cheap manufacturing methods, roll-to-roll compatibility, easy processing capabilities on flexible substrates and exceptional diffuse/low-light performance. This review discusses the recent developments in DSSC materials for its indoor applications. Ultimately, the perspective on this topic is presented after summing up the current progress of the research.

Graphic abstract
ESMO 2020 update: Pancreatic cancer
Authors: Bergen Elisabeth Sophie
Published: April 2021

At the ESMO (European Society for Medical Oncology) 2020 several interesting albeit not practice-changing studies in the field of pancreatic cancer were presented. The Canadian phase II randomized PA.7 trial investigated the additional benefit of dual checkpoint inhibition with durvalumab and tremelimumab to a standard chemotherapy regimen as first-line treatment in patients with metastatic pancreatic ductal adenocarcinoma (mPDAC). Unfortunately, no significant improvement of responses or outcome could be achieved rendering this study a negative trial. Within the German platform-based QoliXane trial, quality of life was shown to be an essential prognosticator of survival with fatigue and nausea being independently associated with outcome of patients. Moreover, promising results could be observed with new targeted therapy approaches, which may lead to its investigation in larger randomized clinical trials.
Death of unknown cause? Post-mortem diagnosis of fulminant course of an EBV-associated secondary hemophagocytic lymphohistiocytosis
Authors: Fauser Josia , Köck Stefan , Gunsilius Eberhard , Chott Andreas , Peer Andreas , Ditlbacher Adelheid , Fritsche Gernot , Joannidis Michael , Wolf Dominik , Pircher Andreas
Published: April 2021

HLH is a life-threatening disease, which is characterized by a dysregulated immune response with uncontrolled T cell and macrophage activation. The often fulminant course of the disease needs a fast diagnostic work-up to initiate as soon as possible the appropriate therapy. We present herein the case of a 71-year-old patient with rapidly progressive hyperinflammatory syndrome, which post mortem resulted in the diagnosis of EBV-associated HLH. With this case report, we intend to highlight the relevance of the HScore in the diagnosis of HLH, to create a greater awareness for EBV as a trigger of HLH, and to demonstrate the importance of treating EBV-associated HLH as early as possible.
Clinically relevant infections in hematology and oncology: bacterial infections and the role of novel antibiotics in times of multidrug resistance
Authors: Fritsche Gernot
Published: April 2021

Multidrug resistance of bacterial pathogens is an increasing problem wordwide, especially treatment of multidrug resistant (MDR) gramnegative bacteria is challenging. In the recent past, several new antibiotics as well as new betalactamase inhibitors have been introduced. These novel drugs are valuable new tools for the therapy of infectious complications in cancer patients once there is a high risk for infections due to multidrug-resistant pathogens. While it is necessary to start empirical antibiotic therapy immediately, novel antibiotics only provide benefits in certain situations, depending on the underlying pathogens. Thus, these new antibiotics are best used guided by microbiological testing, since the exact mechanism of resistance determines susceptibility or resistance to certain antibiotics. For empirical therapy, previous culture results and/or colonization with MDR pathogens can help to choose from conventional antibiotics or novel drugs. In clinical practice, optimal antibiotic therapy can be achieved by close collaboration of specialists in hematooncology, infectious diseases and microbiology.
Japanese subpopulation analysis of MONARCH 2: phase 3 study of abemaciclib plus fulvestrant for treatment of hormone receptor-positive, human epidermal growth factor receptor 2-negative breast cancer that progressed on endocrine therapy
Authors: Inoue Kenichi , Masuda Norikazu , Iwata Hiroji , Takahashi Masato , Ito Yoshinori , Miyoshi Yasuo , Nakayama Takahiro , Mukai Hirofumi , van der Walt Jan-Stefan , Mori Joji , Sakaguchi Sachi , Kawaguchi Tsutomu , Tanizawa Yoshinori , Llombart-Cussac Antonio , Sledge George W. , Toi Masakazu
Published: April 2021

Background

This was a Japanese subpopulation analysis of MONARCH 2, a double-blind, randomized, placebo-controlled, phase 3 study of abemaciclib plus fulvestrant in patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer (ABC).

Methods

Eligible women had progressed on (neo)adjuvant endocrine therapy (ET), ≤ 12 months from end of adjuvant ET, or on first-line ET for ABC, and had not received chemotherapy for ABC. Patients were randomized 2:1 to receive abemaciclib or placebo plus fulvestrant. The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS), pharmacokinetics (PK), health-related quality of life (HRQoL), and safety.

Results

In Japan, 95 patients were randomized (abemaciclib, n = 64; placebo, n = 31). At final PFS analysis (February 14, 2017), median PFS was 21.2 and 14.3 months, respectively, in the abemaciclib and placebo groups (hazard ratio: 0.672; 95% confidence interval: 0.380–1.189). Abemaciclib had a higher objective response rate (37.5%) than placebo (12.9%). PK and safety profiles for Japanese patients were consistent with those of the overall population, without clinically meaningful differences across most HRQoL dimensions evaluated. The most frequent adverse events in the abemaciclib versus placebo groups were diarrhea (95.2 versus 25.8%), neutropenia (79.4 versus 0%), and leukopenia (66.7 versus 0%). At a second data cutoff (June 20, 2019), median OS was not reached with abemaciclib and 47.3 months with placebo (hazard ratio: 0.755; 95% confidence interval: 0.390–1.463).

Conclusions

Results of the Japanese subpopulation were consistent with the improved clinical outcomes and manageable safety profile observed in the overall population.

Clinical trial registration

NCT02107703; U.S. National Library of Medicine: https://clinicaltrials.gov/ct2/show/NCT02107703.
Correction to: Sexual bipotentiality of the olfactory pathway for sexual behavior in goldfish
Authors: Shinohara Yu , Kobayashi Makito
Published: April 2021

A correction to this paper has been published: https://doi.org/10.1007/s12562-021-01507-8
Bildung und Begleitung armutsgefährdeter junger Mütter
Authors: Metzger Marius , Stadelmann Karin A. , Seiterle Nicolette , Kienholz Annina
Published: April 2021

Junge Mütter und deren Kinder sehen sich im Entwicklungsverlauf besonders hohen Risiken ausgesetzt. Insbesondere das Armutsrisikos ist aufgrund der vielfach als überfordernd erlebten Situation, trotz früher Elternschaft auch via Berufsausbildung finanzielle Unabhängigkeit zu erreichen, als hoch zu beurteilen. Aus diesem Grund hat die Schweizer Großstadt Bern im Rahmen von deren Armutsbekämpfungsstrategie ein Pilotangebot für junge Mütter konzipiert, welches deren Lebenssituation durch verschiedene Bildungs- und Begleitmaßnahmen langfristig verbessern soll. Mittels von der Hochschule Luzern – Soziale Arbeit erstellten Prognosen zu zukünftig zu erwartenden Sozialhilfebezügen als zentraler Indikator für eine gelingende Armutsbekämpfung wurde versucht, den Erfolg des Pilotangebotes vorauszusagen. Eine erste Erhebung bei der ersten Kohorte der Teilnehmerinnen des Angebotes zeigt nun, dass sich die Prognosen als stabil erweisen und die jungen Mütter tatsächlich finanzielle Eigenständigkeit erreichen können. Es wird allerdings weitere Erhebungen bei den nachfolgenden Kohorten brauchen, um diese ersten Befunde zu erhärten.
Felder und Akteur*innen kultureller Bildung in ländlichen Räumen
Authors: Thole Werner , Engel Alexandra , Retkowski Alexandra , Drews Katja , Schametat Jan , Gumz Heike , Trostmann Julian
Published: April 2021

Das vom Bundesministerium für Bildung und Forschung (BMBF) geförderte Verbundvorhaben zielt auf eine empirisch fundierte Darstellung der kulturellen Landschaften und insbesondere der Akteur*innenkonstellationen der kulturellen Bildung in drei alsperipherbissehr periphergekennzeichneten Regionen. Konkret wird mittels quantitativer und qualitativer Erhebungsmethoden den Fragestellungen nachgegangen, welche Felder und Akteur*innen in welcher Form und mit welchen Angeboten den Kultursektor bespielen, welche Vernetzungsformen und Kooperationen bestehen, wie diese und wie auch die Praxis und die Praktiken hergestellt und mit welchen Sinnkonstruktionen von den engagierten Personen versehen werden. Die Studie strebt an, neben der Identifikation der Spezifika kultureller Arrangements in den drei ländlichen Räumen diese auch vergleichend zu beschreiben.
Pore-Scale Modeling of Anode Catalyst Layer Tolerance upon Hydrogen Sulfide Exposure in PEMFC
Authors: Hou Yuze , Prass Sebastian , Li Xing , Du Qing , Jiao Kui , Zamel Nada
Published: April 2021

A pore-scale contamination model is developed to resolve the physicochemical processes in the anode catalyst layer for a deeper insight into the hydrogen sulfide (H2S) contamination mechanism. The present model is based on lattice Boltzmann method (LBM) and a novel iteration algorithm is coupled to overcome the time-scale issue in LBM which can extend its application. The microstructure of CL is stochastically reconstructed considering the presence of carbon, Pt, ionomer, and pores. The proposed model is validated by comparing the experimental data and can accurately predict the effect of H2S contamination on performance with time. The results show that the fuel cell performance is not sensitive to the anode Pt loading under the clean fuel condition as the hydrogen oxidation reaction is easy to activate. However, higher Pt loading can effectively prolong the operation time under the H2S contamination by providing a larger buffer reactive area and a lower H2S concentration condition. Furthermore, the H2S contamination in the fuel gas should be strictly restricted as it directly affects the poisoning rate and significantly affects the operation time.

Graphical abstract

Physicochemical processes in the ACL with reactant transport through micro porous layer (MPL) to active Pt sites
Stirred tank simulation using Partially-Averaged Navier-Stokes $$k_u-\epsilon _u$$ turbulence model
Authors: Maji Srimanta , Sahu Akshaya K.
Published: April 2021

In the present study, simulation of a stirred tank using axial flow impeller has been studied numerically to see the behaviour of flow variables in the entire vessel. It is assumed that the flow is steady state, two dimensional, incompressible and axisymmetric. For simulation, Partially-Averaged Navier-Stokes (PANS) $$k_u-\epsilon _u$$

k
u

-

ϵ
u

turbulence model has been taken into account. For discretization, control volume method along with upwind and power-law schemes have been taken. The solutions are obtained by using the SIMPLE algorithm. The boundary conditions for impeller are given by using the experimental data. The main objective is to investigate the influence of different filters width $$f_k$$

f
k

of the PANS $$k_u-\epsilon _u$$

k
u

-

ϵ
u

model parameter on the characteristic flow variables. The predicted results of the PANS $$k_u-\epsilon _u$$

k
u

-

ϵ
u

model for different $$f_k$$

f
k

have been compared with the experimental data at different axial levels of the stirred tank. It has been observed that the power-law scheme gives better agreement with the experimental data. Further, near the impeller region, PANS predicted results are better for smaller $$f_k$$

f
k

. Also, Reynolds-Averaged Navier-Stokes Shear Stress Transport (SST) $$k-\omega $$

k
-
ω

turbulence model has been tested for comparative study.
Radio Frequency Integrated Circuits and Systems
Authors: Darabi Hooman
Published: April 2021

This updated and expanded new edition equips students with a thorough understanding of the state-of-the-art in radio frequency (RF) design and the practical knowledge and skills needed in industry. Introductory and advanced topics are covered in-depth, with clear step-by-step explanations, including core topics such as RF components, signals and systems, two-ports, noise, distortion, low-noise amplifiers, power amplifiers, and transceiver architectures. New material has been added on wave propagation, skin effect, antennas, mixers and oscillators, and digital PAs and transmitters. Two new chapters detail the analysis and design of RF and IF filters (including SAW and FBAR duplexers and N-path filters), phase-locked loops, frequency synthesizers, digital PLLs, and frequency dividers. Theory is linked to practice through real-world applications, practical design examples, and exploration of the pros and cons of various topologies. Over 250 homework problems are included, with solutions and lecture slides for instructors available online. With its uniquely practical and intuitive approach, this is an essential text for graduate courses on RFICs and a useful reference for practicing engineers.
Lawful Remedy or Illegal Response? Resolving the Issue of Foreign Subsidization under WTO Law
Authors: Crochet Victor , Gustafsson Marcus
Published: April 2021

Discontentment is growing such that governments, and notably that of China, are increasingly providing subsidies to companies outside their jurisdiction, ‘buying their way’ into other countries’ markets and undermining fair competition therein as they do so. In response, the European Union recently published a proposal to tackle such foreign subsidization in its own market. This article asks whether foreign subsidies can instead be addressed under the existing rules of the World Trade Organization, and, if not, whether those rules allow States to take matters into their own hands and act unilaterally. The authors shed light on these issues and provide preliminary guidance on how to design a response to foreign subsidization which is consistent with international trade law.
Virtuelle Simulationen in der Pflegeausbildung
Authors: Obermeier Lisa , Jänicke-Stöger Tanja
Published: April 2021

Zusammenfassung. Die pandemiebedingten Einschränkungen stellen Akteure im Gesundheitswesen, insbesondere in der Pflegeausbildung, vor immense Herausforderungen. Zur Gewährleistung eines kontinuierlichen Lehrbetriebs werden Lerninhalte mittels digitaler Lernformen vermittelt. Doch wie kann simulationsbasiertes Lernen in virtueller Form umgesetzt werden? Kreativität, Improvisation und unkonventionelle Lösungsansätze sind gefragt.
Auszubildende auf einer Gratwanderung im Umgang mit Bettlägerigen
Authors: Kanike-Schmidt Christine
Published: April 2021

Zusammenfassung. Auszubildende der Gesundheits- und Krankenpflegeausbildung sind wiederkehrend mit dem Phänomen der Bettlägerigkeit konfrontiert. Zur Bewältigung der praktischen Herausforderung benötigen sie eine theoretische Grundlage und Hilfestellung bei der Umsetzung von Bewegungskonzepten in der individuellen Situationseinschätzung.
Individual Differences in Romantic Attachment
Authors: Bleske-Rechek April , Nuck Grace , Gunseor Michaela M.
Published: April 2021

Abstract. In the 1980s, psychologists extended attachment theory into the domain of adult romantic bonds by proposing that romantic love can be conceptualized as a process of becoming attached ( Hazan & Shaver, 1987 ). From this perspective, individuals differ in two primary attachment dimensions: anxiety, the extent to which they worry about abandonment in their romantic relationships, and avoidance, the extent to which they are uncomfortable with interdependence and closeness. Research suggests that people perceive the rearing environment as a primary cause of people’s romantic attachment styles ( Tillman et al., 2008 ). If it is, family members should be similar in attachment-related anxiety and avoidance. To test this idea, we collected romantic attachment data on 965 US college students and the family members they nominated (205 siblings, 245 mothers, and 182 fathers). The students and family members in our sample showed negligible-to-weak resemblance in attachment-related anxiety and avoidance. Because previous studies have shown substantial similarity between identical twins and weak similarity between fraternal twins in romantic attachment styles, our data reinforce the possibility that nonshared environmental influences (such as individuals’ specific relationship histories) and genetic influences are the primary sources of individual differences in attachment-related anxiety and avoidance.
GPS Imaging of Vertical Bedrock Displacements: Quantification of Two‐Dimensional Vertical Crustal Deformation in China
Authors: Pan Yuanjin , Hammond William C. , Ding Hao , Mallick Rishav , Jiang Weiping , Xu Xinyu , Shum C. K. , Shen Wenbin
Published: April 2021

The Global Positioning System (GPS) derived bedrock displacements respond to multiple geophysical effects, ranging from surface elastic loads to tectonic sources or viscoelastic uplifts stemming from Earth’s viscous mantle. In this study, the GPS‐inferred vertical crustal velocities are rigorously estimated in mainland China. We integrate the GPS vertical velocity field with Gravity Recovery and Climate Experiment (GRACE) and GRACE Follow‐On (GFO) data, adopting an empirical Spatial Structure Function (SSF), to image tectonic deformation in mainland China with respect to the International Terrestrial Reference Frame (ITRF) 2014. We present four profiles across China, which indicate that our new robust results are superior to kriging. Furthermore, we use the GRACE/GFO products to account for elastic deformation due to surface mass changes to isolate tectonic deformation signals at GPS sites within mainland China from 2002 to 2019. By integrating GPS and GRACE/GFO measurements, our results reveal the long‐term spatial patterns of vertical tectonic motion in different blocks in mainland China. We conclude that significant steep velocity gradients occur at tectonic block boundaries that are attributable to locking and elastic strain accumulation on active block boundary faults.
Analysis of Crystalline Rock Permeability Versus Depth in a Canadian Precambrian Rock Setting
Authors: Snowdon Andrew P. , Normani Stefano D. , Sykes Jonathan F.
Published: April 2021

Over the last 50 years, there has been an increased interest in characterizing Precambrian crystalline rock, such as the Canadian Shield, to investigate the feasibility of deep geologic repositories for isolating used nuclear fuel from the biosphere. Extensive work has been conducted in Canada with a large amount of that work undertaken by Atomic Energy of Canada Limited. Few peer‐reviewed journal articles were published based on these data, so a large amount of the data, specifically on fracture zones, are unavailable for modelers and analysts. By collecting and analyzing over one‐hundred technical reports, journal articles, and conference proceedings, written between 1975 and 1996, it was possible to characterize plutonic Precambrian crystalline rock and separate the data into (1) equivalent porous media (EPM) for rock mass and (2) fracture zones (FZs). A third category, aggregate media (AM), was used herein to represent the entire data set (EPM + FZs). Using the data from these studies, a novel logistic function was fit to represent the mean permeability, with respect to depth, of crystalline rock for EPMs and FZs in plutons. Understanding rock permeability is critical for the long‐term isolation of used nuclear fuel so that accurate predictions of fluid flow and mass transport can be evaluated in the area of the proposed storage location.
Contribution of Snow to Arctic First‐Year and Multi‐Year Sea Ice Mass Balance Within the Last Ice Area
Authors: Lange Benjamin A. , Haas Christian , Mucci Alfonso , Beckers Justin F. , Casey J. Alec , Duerksen Steve , Granskog Mats A. , Hatam Ido , Niemi Andrea , Reppchen Anke , Michel Christine
Published: April 2021

We present the δ18O isotope composition of 16 multi‐year ice (MYI) and eight first‐year ice (FYI) cores collected during spring from the Lincoln Sea, a region within the Last Ice Area, which is expected to retain MYI longest into the future. Isotopic signatures were used to quantify the contribution of snow to sea ice mass. These estimates yield a higher total snow contribution in MYI (10 ± 5%) than to FYI (4 ± 2%). Converted to Snow Depth Equivalent (SDE), MYI had five times larger SDE (0.79 ± 0.38 m) than FYI (0.16 ± 0.11 m). The difference is explained by the contribution of refrozen surface and under‐ice melt ponds as well as superimposed/interposed ice for MYI resulting from higher accumulation of snow over multiple, longer accumulation seasons compared to FYI. Given the impending replacement of MYI by FYI, the large difference in absolute snow contributions between MYI and FYI highlights the potential implications in terms of the redistribution of precipitation‐derived (meteoric) freshwater throughout the Arctic Ocean. Furthermore, we observed high relative snow contributions to ice mass in the surface of one‐third of older FYI cores, which we attributed to flooding and formation of snow‐ice. Our results support the premise that flooding events on FYI may be more prevalent throughout the Arctic Ocean than previously assumed.
Carbon Dioxide Distribution, Origins, and Transport Along a Frontal Boundary During Summer in Mid‐Latitudes
Authors: Samaddar Arkayan , Feng Sha , Lauvaux Thomas , Barkley Zachary R. , Pal Sandip , Davis Kenneth J.
Published: April 2021

Synoptic weather systems are a major driver of spatial gradients in atmospheric CO2 mole fractions. During frontal passages, air masses from different regions meet at the frontal boundary creating significant gradients in CO2 mole fractions. We quantitatively describe the atmospheric transport of CO2 mole fractions during a mid‐latitude cold front passage and explore the impact of various sources of CO2. We focus here on a cold front passage over Lincoln, Nebraska on August 4th, 2016 observed by aircraft during the Atmospheric Carbon and Transport‐America campaign. A band of air with elevated CO2 was located along the frontal boundary. Observed and simulated differences in CO2 across the front were as high as 25 ppm. Numerical simulations using Weather Research and Forecasting Model with Chemistry at cloud resolving resolutions (3 km), coupled with CO2 surface fluxes and boundary conditions from CarbonTracker (CT‐NRTv2017x), were performed to explore atmospheric transport at the front. Model results demonstrate that the frontal CO2 difference in the upper troposphere can be explained largely by inflow from outside of North America. This difference is modified in the atmospheric boundary layer and lower troposphere by continental surface fluxes, dominated in this case by biogenic and fossil fuel fluxes. Horizontal and vertical advection are found to be responsible for the transport of CO2 mole fractions along the frontal boundary. We show that cold front passages lead to large CO2 transport events including a significant contribution from vertical advection, and that midcontinent frontal boundaries are formed from a complex mixture of CO2 sources.
The Impact of Split and Displacement Sudden Stratospheric Warmings on the Troposphere
Authors: White Ian P. , Garfinkel Chaim I. , Cohen Judah , Jucker Martin , Rao Jian
Published: April 2021

Although sudden stratospheric warmings (SSWs) can improve subseasonal‐to‐seasonal forecasts, it is unclear whether the two types of SSW ‐ displacements and splits ‐ have different near‐surface effects. To examine the longer‐term (i.e., multi‐week lead) tropospheric response to displacements and splits, we utilize an intermediate‐complexity model and impose wave‐1 and wave‐2 stratospheric heating perturbations spun‐off from a control run. At longer lags, the tropospheric response is found to be insensitive to both the wavenumber and location of the imposed heating, in agreement with freely evolving displacements and splits identified in the control run. At shorter lags, however, large differences are found between displacements and splits in both the control run and the different wavenumber‐forced events. In particular, in the control run, the free‐running splits have an immediate barotropic response throughout the stratosphere and troposphere whereas displacements take 1–2 weeks before a near‐surface response becomes evident. Interestingly, this barotropic response found during CTRL splits is not captured by the barotropically forced wave‐2 events, indicating that the zonal‐mean tropospheric circulation is somehow coupled with the generation of the wave‐2 splits. It is also found that in the control run, displacements yield stronger Polar‐Cap temperature anomalies than splits, yet both still yield similar magnitude tropospheric responses. Hence, the strength of the stratospheric warming is not the only governing factor in the surface response. Overall, SSW classification based on vortex morphology may be useful for subseasonal but not seasonal tropospheric prediction.
Monsoon Clouds Control the Summer Surface Energy Balance on East Rongbuk Glacier (6,523 m Above Sea Level), the Northern of Mt. Qomolangma (Everest)
Authors: Liu Weigang , Zhang Dongqi , Qin Xiang , van den Broeke Michiel R. , Jiang Youyan , Yang Diyi , Ding Minghu
Published: April 2021

To identify the atmospheric controls of the summertime glacier surface energy balance in the Himalayas, in situ meteorological data collected at 6,523 m above sea level during May–July 2005 were obtained and analyzed. Our results showed that net shortwave radiation (103 W m−2) and turbulent sensible heat flux (12 W m−2) acted as energy sources, and net longwave radiation (−62 W m−2) and turbulent latent heat flux (−20 W m−2) represented heat sinks. Cloud cover controlled the summer surface energy balance. During the active period of the South Asian Summer Monsoon, the frequent cloud coverage increased the incoming longwave radiation more than it decreased the incident solar radiation. Intensification (weakening) of the South Asian Summer Monsoon strengthened (suppressed) surface melting. The melt energy measured during the nonmonsoon period was small due to the energy consumption associated with glacier volume warming, energy loss from sublimation, and large heat loss through net longwave radiation due to the low amount of incoming longwave radiation caused by the low cloudiness. The comparison of glacier surface energy balances on the Tibetan Plateau shows that on continental glaciers, net radiation is lower and accounts for a smaller contribution to energy sources, and the dominant energy sinks are sublimation and evaporation, rather than melting, which is the primary energy sink for maritime/subcontinental glaciers. This implies an important spatial variability in glacial sensitivity to different climatic conditions on the Tibetan Plateau.
Targeting the glucocorticoid receptor signature gene Mono Amine Oxidase-A enhances the efficacy of chemo- and anti-androgen therapy in advanced prostate cancer
Authors: Puhr Martin , Eigentler Andrea , Handle Florian , Hackl Hubert , Ploner Christian , Heidegger Isabel , Schaefer Georg , Brandt Maximilian P. , Hoefer Julia , Van der Pluijm Gabri , Klocker Helmut
Published: April 2021

Despite increasing options for treatment of castration-resistant prostate cancer, development of drug resistance is inevitable. The glucocorticoid receptor (GR) is a prime suspect for acquired therapy resistance, as prostate cancer (PCa) cells are able to increase GR signaling during anti-androgen therapy and thereby circumvent androgen receptor (AR)-blockade and cell death. As standard AR-directed therapies fail to block the GR and GR inhibitors might result in intolerable side effects, the identification of GR signature genes, which are better suited for a targeted approach, is of clinical importance. Therefore, the specific epithelial and stromal GR signature was determined in cancer-associated fibroblasts as well as in abiraterone and enzalutamide-resistant cells after glucocorticoid (GC) treatment. Microarray and ChIP analysis identified MAO-A as a directly up-regulated mutual epithelial and stromal GR target, which is induced after GC treatment and during PCa progression. Elevated MAO-A levels were confirmed in in vitro cell models, in primary tissue cultures after GC treatment, and in patients after neoadjuvant chemotherapy with GCs. MAO-A expression correlates with GR/AR activity as well as with a reduced progression-free survival. Pharmacological MAO-A inhibition combined with 2nd generation AR signaling inhibitors or chemotherapeutics results in impaired growth of androgen-dependent, androgen-independent, and long-term anti-androgen-treated cells. In summary, these findings demonstrate that targeting MAO-A represents an innovative therapeutic strategy to synergistically block GR and AR dependent PCa cell growth and thereby overcome therapy resistance.
FOXO3 is a latent tumor suppressor for FOXO3-positive and cytoplasmic-type gastric cancer cells
Authors: Tsuji Toshikatsu , Maeda Yusuke , Kita Kenji , Murakami Kazuhiro , Saya Hideyuki , Takemura Hirofumi , Inaki Noriyuki , Oshima Masanobu , Oshima Hiroko
Published: April 2021

FOXO3 is a member of the FOXO transcription factors thought to play a tumor-suppressor role in gastrointestinal cancer, while tumor-promoting function of FOXO3 has also been reported. These results suggest a context-dependent function of FOXO3 in tumor development. However, the relationship between the FOXO3 expression pattern and its role in tumorigenesis has not been elucidated. We examined the FOXO3 expression in 65 human primary gastric cancer and patient-derived xenograft tissues by immunohistochemistry and identified three subtypes according to subcellular localization: FOXO3-nuclear accumulated (FOXO3-Nuc), FOXO3-nuclear/cytoplasmic or cytoplasmic distributed (FOXO3-Cyt), and FOXO3-negative. In the FOXO3-Cyt gastric cancer cells, the expression of the constitutive active mutant FOXO3 (Act-ER FOXO3) induced the nuclear accumulation of FOXO3 and significantly suppressed colony formation and proliferation. The inhibition of the PI3K-AKT pathway by inhibitor treatment also suppressed the proliferation of FOXO3-Cyt gastric cancer cells, which was associated with the nuclear accumulation of endogenous FOXO3. Furthermore, the expression of Act-ER FOXO3 by an endogenous promoter significantly suppressed gastric tumorigenesis in Gan mice, a model of gastric cancer. Finally, treatment of FOXO3-Cyt human gastric cancer-derived organoids with an AKT inhibitor significantly suppressed the survival and proliferation. These results indicate that FOXO3 is a latent tumor suppressor for FOXO3-Cyt-type gastric cancer cells and that activation of the PI3K-AKT pathway protects this type of gastric cancer cell from FOXO3-mediated growth suppression via constitutive nuclear export. Thus, the inhibition of the PI3K-AKT pathway and nuclear translocation of endogenous FOXO3 may have therapeutic applications in the treatment of FOXO3-positive and cytoplasmic-type gastric cancer.
Patent ductus arteriosus, tracheal ventilation, and the risk of bronchopulmonary dysplasia
Authors: Clyman Ronald I. , Hills Nancy K. , Cambonie Gilles , Debillon Thierry , Ligi Isabelle , Gascoin Geraldine , Patkai Juliana , Beuchee Alain , Favrais Geraldine , Durrmeyer Xavier , Flamant Cyril , Rozé Jean Christophe
Published: April 2021

Background

An increased risk for bronchopulmonary dysplasia (BPD) exists when moderate-to-large patent ductus arteriosus shunts (hsPDA) persist beyond 14 days.

Goal

To examine the interaction between prolonged exposures to tracheal ventilation (≥10 days) and hsPDA on the incidence of BPD in infants <28 weeks gestation.

Study Design

Predefined definitions of prolonged ventilation (≥10 days), hsPDA (≥14 days), and BPD (room air challenge test at 36 weeks) were used to analyze deidentified data from the multicenter TRIOCAPI RCT in a secondary analysis of the trial.

Results

Among 307 infants who survived >14 days, 41 died before 36 weeks. Among survivors, 93/266 had BPD. The association between BPD and hsPDA depended on the length of intubation. In multivariable analyses, prolonged hsPDA shunts were associated with increased BPD (odds ratio (OR) (95% confidence interval (CI)) = 3.00 (1.58–5.71)) when infants required intubation for ≥10 days. In contrast, there was no significant association between hsPDA exposure and BPD when infants were intubated <10 days (OR (95% CI) = 1.49 (0.98–2.26)). A similar relationship between prolonged hsPDA and length of intubation was found for BPD/death (n = 307): infants intubated ≥10 days: OR (95% CI) = 2.41 (1.47–3.95)); infants intubated <10 days: OR (95% CI) = 1.37 (0.86–2.19)).

Conclusions

Moderate-to-large PDAs were associated with increased risks of BPD and BPD/death—but only when infants required intubation ≥10 days.

Impact

Infants with a moderate-to-large hsPDA that persist beyond 14 days are only at risk for developing BPD if they also receive prolonged tracheal ventilation for ≥10 days.

Infants who receive less ventilatory support (intubation for <10 days) have the same incidence of BPD whether the ductus closes shortly after birth or whether it persists as a moderate-to-large shunt for several weeks.

Early PDA closure may be unnecessary in infants who require short durations of intubation since the PDA does not seem to alter the incidence of BPD in infants who require intubation for <10 days.
Circ-ITCH sponges miR-214 to promote the osteogenic differentiation in osteoporosis via upregulating YAP1
Authors: Zhong Da , Xu Gan-Zhe , Wu Ju-Zhi , Liu Hua , Tang Ju-Yu , Wang Cheng-Gong
Published: April 2021

Osteoporosis is the most prevailing primary bone disease and a growing health care burden. The aim of this study was to clarify the functional roles and mechanisms of the circ-ITCH regulating osteogenic differentiation of osteoporosis. Circ-ITCH and yes-associated protein 1 (YAP1) levels were downregulated, but the miR‐214 level was upregulated in osteoporotic mice and patients. Knockdown of circ-ITCH inhibited the alkaline phosphatase (ALP) activity, mineralized nodule formation, and expression of runt-related transcription factor 2 (RUNX2), osteopontin (OPN), and osteocalcin (OCN) during osteogenic induction. Furthermore, miR-214 was a target of circ-ITCH, knockdown of miR-214 could impede the regulatory effects of sh-circ-ITCH on osteogenic differentiation. Moreover, miR-214 suppressed hBMSCs osteogenic differentiation by downregulating YAP1. Finally, in vivo experiments indicated that overexpression of circ-ITCH could improve osteogenesis in ovariectomized mice. In conclusion, circ-ITCH upregulated YAP1 expression to promote osteogenic differentiation in osteoporosis via sponging miR-214. Circ-ITCH could act as a novel therapeutic target for osteoporosis.
SENP1-mediated deSUMOylation of JAK2 regulates its kinase activity and platinum drug resistance
Authors: Li Jing , Wu Ruiqin , Yung Mingo M. H. , Sun Jing , Li Zhuqing , Yang Hai , Zhang Yi , Liu Stephanie S. , Cheung Annie N. Y. , Ngan Hextan Y. S. , Braisted John C. , Zheng Wei , Wei Huiqiang , Gao Yingtang , Nemes Peter , Pei Huadong , Chan David W. , Li Yiliang , Zhu Wenge
Published: April 2021

The JAK2/STAT pathway is hyperactivated in many cancers, and such hyperactivation is associated with a poor clinical prognosis and drug resistance. The mechanism regulating JAK2 activity is complex. Although translocation of JAK2 between nucleus and cytoplasm is an important regulatory mechanism, how JAK2 translocation is regulated and what is the physiological function of this translocation remain largely unknown. Here, we found that protease SENP1 directly interacts with and deSUMOylates JAK2, and the deSUMOylation of JAK2 leads to its accumulation at cytoplasm, where JAK2 is activated. Significantly, this novel SENP1/JAK2 axis is activated in platinum-resistant ovarian cancer in a manner dependent on a transcription factor RUNX2 and activated RUNX2/SENP1/JAK2 is critical for platinum-resistance in ovarian cancer. To explore the application of anti-SENP1/JAK2 for treatment of platinum-resistant ovarian cancer, we found SENP1 deficiency or treatment by SENP1 inhibitor Momordin Ic significantly overcomes platinum-resistance of ovarian cancer. Thus, this study not only identifies a novel mechanism regulating JAK2 activity, but also provides with a potential approach to treat platinum-resistant ovarian cancer by targeting SENP1/JAK2 pathway.
EBV-LMP1 promotes radioresistance by inducing protective autophagy through BNIP3 in nasopharyngeal carcinoma
Authors: Xu San , Zhou Zhuan , Peng Xingzhi , Tao Xuxiu , Zhou Peijun , Zhang Kun , Peng Jinwu , Li Dan , Shen Liangfang , Yang Lifang
Published: April 2021

Studies have indicated that dysfunction of autophagy is involved in the initiation and progression of multiple tumors and their chemoradiotherapy. Epstein–Barr virus (EBV) is a lymphotropic human gamma herpes virus that has been implicated in the pathogenesis of nasopharyngeal carcinoma (NPC). EBV encoded latent membrane protein1 (LMP1) exhibits the properties of a classical oncoprotein. In previous studies, we experimentally demonstrated that LMP1 could increase the radioresistance of NPC. However, how LMP1 contributes to the radioresistance in NPC is still not clear. In the present study, we found that LMP1 could enhance autophagy by upregulating the expression of BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 (BNIP3). Knockdown of BNIP3 could increase the apoptosis and decrease the radioresistance mediated by protective autophagy in LMP1-positive NPC cells. The data showed that increased BNIP3 expression is mediated by LMP1 through the ERK/HIF1α signaling axis, and LMP1 promotes the binding of BNIP3 to Beclin1 and competitively reduces the binding of Bcl-2 to Beclin1, thus upregulating autophagy. Furthermore, knockdown of BNIP3 can reduce the radioresistance promoted by protective autophagy in vivo. These data clearly indicated that, through BNIP3, LMP1 induced autophagy, which has a crucial role in the protection of LMP1-positive NPC cells against irradiation. It provides a new basis and potential target for elucidating LMP1-mediated radioresistance.
LDHA induces EMT gene transcription and regulates autophagy to promote the metastasis and tumorigenesis of papillary thyroid carcinoma
Authors: Hou Xiukun , Shi Xianle , Zhang Wei , Li Dapeng , Hu Linfei , Yang Jihong , Zhao Jingzhu , Wei Songfeng , Wei Xi , Ruan Xianhui , Zheng Xiangqian , Gao Ming
Published: April 2021

Papillary thyroid carcinoma (PTC) is one of the most common kinds of endocrine-related cancer and has a heterogeneous prognosis. Metabolic reprogramming is one of the hallmarks of cancers. Aberrant glucose metabolism is associated with malignant biological behavior. However, the functions and mechanisms of glucose metabolism genes in PTC are not fully understood. Thus, data from The Cancer Genome Atlas database were analyzed, and lactate dehydrogenase A (LDHA) was determined to be a potential novel diagnostic and therapeutic target for PTCs. The research objective was to investigate the expression of LDHA in PTCs and to explore the main functions and relative mechanisms of LDHA in PTCs. Higher expression levels of LDHA were found in PTC tissues than in normal thyroid tissues at both the mRNA and protein levels. Higher expression levels of LDHA were correlated with aggressive clinicopathological features and poor prognosis. Moreover, we found that LDHA not only promoted PTC migration and invasion but also enhanced tumor growth both in vitro and in vivo. In addition, we revealed that the metabolic products of LDHA catalyzed induced the epithelial–mesenchymal transition process by increasing the relative gene H3K27 acetylation. Moreover, LDHA knockdown activated the AMPK pathway and induced protective autophagy. An autophagy inhibitor significantly enhanced the antitumor effect of FX11. These results suggested that LDHA enhanced the cell metastasis and proliferation of PTCs and may therefore become a potential therapeutic target for PTCs.
Fluid as a critical biomarker in neovascular age-related macular degeneration management: literature review and consensus recommendations
Authors: Kodjikian Laurent , Parravano Mariacristina , Clemens Andreas , Dolz-Marco Rosa , Holz Frank G. , Munk Marion R. , Nicolò Massimo , Ricci Federico , Silva Rufino , Talks S. James , Verma Rohini Kumar , Zarranz-Ventura Javier , Zweifel Sandrine A.
Published: April 2021

Current guidelines on the management of patients with neovascular age-related macular degeneration (nAMD) lack clear recommendations on the interpretation of fluid as seen on optical coherence tomography (OCT) imaging and the incorporation of this information into an ongoing disease treatment strategy. Our objective was to review current guidelines and scientific evidence on the role of fluid as a biomarker in the management of nAMD, and develop a clinically oriented, practical algorithm for diagnosis and management based on a consensus of expert European retinal specialists. PubMed was searched for articles published since 2006 relating to the role of fluid in nAMD. A total of 654 publications were screened for relevance and 66 publications were included for review. Of these, 14 were treatment guidelines, consensus statements and systematic reviews or meta-analyses, in which OCT was consistently recommended as an important tool in the initial diagnosis and ongoing management of nAMD. However, few guidelines distinguished between types of fluid when providing recommendations. A total of 52 publications reported primary evidence from clinical trials, studies, and chart reviews. Observations from these were sometimes inconsistent, but trends were observed with regard to features reported as being predictive of visual outcomes. Based on these findings, diagnostic recommendations and a treatment algorithm based on a treat-and-extend (T&E) regimen were developed. These provide guidance on the diagnosis of nAMD as well as a simple treatment pathway based on the T&E regimen, with treatment decisions made according to the observations of fluid as a critical biomarker for disease activity.
Research advances in and prospects of ornamental plant genomics
Authors: Zheng Tangchun , Li Ping , Li Lulu , Zhang Qixiang
Published: April 2021

The term ‘ornamental plant’ refers to all plants with ornamental value, which generally have beautiful flowers or special plant architectures. China is rich in ornamental plant resources and known as the “mother of gardens”. Genomics is the science of studying genomes and is useful for carrying out research on genome evolution, genomic variations, gene regulation, and important biological mechanisms based on detailed genome sequence information. Due to the diversity of ornamental plants and high sequencing costs, the progress of genome research on ornamental plants has been slow for a long time. With the emergence of new sequencing technologies and a reduction in costs since the whole-genome sequencing of the first ornamental plant (Prunus mume) was completed in 2012, whole-genome sequencing of more than 69 ornamental plants has been completed in <10 years. In this review, whole-genome sequencing and resequencing of ornamental plants will be discussed. We provide analysis with regard to basic data from whole-genome studies of important ornamental plants, the regulation of important ornamental traits, and application prospects.
Molecular and physiological characterization of the effects of auxin-enriched rootstock on grafting
Authors: Zhai Longmei , Wang Xiaomin , Tang Dan , Qi Qi , Yer Huseyin , Jiang Xiangning , Han Zhenhai , McAvoy Richard , Li Wei , Li Yi
Published: April 2021

Abstracts

Grafting is a highly useful technique, and its success largely depends on graft union formation. In this study, we found that root-specific expression of the auxin biosynthetic gene iaaM in tobacco, when used as rootstock, resulted in more rapid callus formation and faster graft healing. However, overexpression of the auxin-inactivating iaaL gene in rootstocks delayed graft healing. We observed increased endogenous auxin levels and auxin-responsive DR5::GUS expression in scions of WT/iaaM grafts compared with those found in WT/WT grafts, which suggested that auxin is transported upward from rootstock to scion tissues. A transcriptome analysis showed that auxin enhanced graft union formation through increases in the expression of genes involved in graft healing in both rootstock and scion tissues. We also observed that the ethylene biosynthetic gene ACS1 and the ethylene-responsive gene ERF5 were upregulated in both scions and rootstocks of the WT/iaaM grafts. Furthermore, exogenous applications of the ethylene precursor ACC to the junction of WT/WT grafts promoted graft union formation, whereas application of the ethylene biosynthesis inhibitor AVG delayed graft healing in WT/WT grafts, and the observed delay was less pronounced in the WT/iaaM grafts. These results demonstrated that elevated auxin levels in the iaaM rootstock in combination with the increased auxin levels in scions caused by upward transport/diffusion enhanced graft union formation and that ethylene was partially responsible for the effects of auxin on grafting. Our findings showed that grafting success can be enhanced by increasing the auxin levels in rootstocks using transgenic or gene-editing techniques.