bluuebunny/crossref_metadata_2025 huggingface dataset:
On membership of the United Nations and the State of Palestine: A critical account
Authors: Imseis Ardi
Published: August 2021

Against the context of pending judicial proceedings between the State of Palestine and the United States of America (US) at the International Court of Justice (ICJ), this article critically examines the United Nations (UN) commitment to the international rule of law through an examination of its consideration of Palestine’s 2011 application for membership in the organization. The universality of membership of the UN is a foundation upon which the organization rests. The international law governing UN admission has accordingly been marked by a liberal, flexible and permissive interpretation of the test for membership contained in the UN Charter. In contrast, an assessment of the UN’s consideration of Palestine’s application for membership demonstrates that it was subjected to an unduly narrow, strict and resultantly flawed application of the membership criteria. An examination of the contemporaneous debates of the Council demonstrates that the main driver of this was the US, which used its legal authority as a permanent member of the Council to block Palestine’s membership. The principle argument used against membership was the US’s view that Palestine does not qualify as a state under international law. Notwithstanding, the State of Palestine has been recognized by 139 member states of the UN and has acceded to a number of treaties that furnish it with access to the ICJ. While a number of articles have been written about Palestine’s statehood, little has been written on the UN’s consideration of Palestine’s 2011 application for membership. Palestine v. USA provides a renewed opportunity to do so.
Effects of air-conditioning systems in the public areas of hospitals: A scoping review
Authors: Ting Wu Han , Shuang Li Qiu , Chen Dai Rong , Liu Shan , Wu Li , Mao Wei , Hua Ji Cong
Published: August 2021

Almost all hospitals are equipped with air-conditioning systems to provide a comfortable environment for patients and staff. However, the accumulation of dust and moisture within these systems increases the risk of transmission of microbes and have on occasion been associated with outbreaks of infection. Nevertheless, the impact of air-conditioning on the transmission of microorganisms leading to infection remains largely uncertain. We conducted a scoping review to screen systematically the evidence for such an association in the face of the coronavirus disease 2019 epidemic. PubMed, Embase and Web of Science databases were explored for relevant studies addressing microbial contamination of the air, their transmission and association with infectious diseases. The review process yielded 21 publications, 17 of which were cross-sectional studies, three were cohort studies and one case−control study. Our analysis showed that, compared with naturally ventilated areas, microbial loads were significantly lower in air-conditioned areas, but the incidence of infections increased if not properly managed. The use of high-efficiency particulate air (HEPA) filtration not only decreased transmission of airborne bioaerosols and various microorganisms, but also reduced the risk of infections. By contrast, contaminated air-conditioning systems in hospital rooms were associated with a higher risk of patient infection. Cleaning and maintenance of such systems to recommended standards should be performed regularly and where appropriate, the installation of HEPA filters can effectively mitigate microbial contamination in the public areas of hospitals.
Mumps outbreak among fully vaccinated school-age children and young adults, Portugal 2019/2020
Authors: Perez Duque Mariana , San-Bento Ana , Léon Lourdes , Custódio Paula , Esperança Maria Anjos , Albuquerque Maria João , Nascimento Marina , Balasegaram Sooria , Sá Machado Rita
Published: August 2021

On 16–17 January 2020, four suspected mumps cases were reported to the local Public Health Authorities with an epidemiological link to a local school and football club. Of 18 suspected cases identified, 14 were included in this study. Laboratory results confirmed mumps virus as the cause and further sequencing identified genotype G. Our findings highlight that even with a high MMR vaccine coverage, mumps outbreaks in children and young adults can occur. Since most of the cases had documented immunity for mumps, we hypothesise that waning immunity or discordant mumps virus strains are likely explanations for this outbreak.
Sensitivity of Carbonaceous Aerosol Properties to the Implementation of a Dynamic Aging Parameterization in the Regional Climate Model RegCM
Authors: Ghosh Sudipta , Riemer Nicole , Giuliani Graziano , Giorgi Filippo , Ganguly Dilip , Dey Sagnik
Published: August 2021

Freshly emitted soot is hydrophobic, but condensation of secondary aerosols and coagulation with other particles modify its hygroscopic optical properties. This conversion is referred to as “aerosol aging.” Many climate models represent this aging process with a fixed aging time scale, whereas in reality, it is a dynamic process that depends on environmental conditions. Here, we implement a dynamic aging parameterization scheme in the regional climate model RegCM4 in place of the fixed aging timescale of 1.15 days (∼27.6 h) and examine its impact on the aerosol life cycle over the Indian subcontinent. The conversion from hydrophobic to hydrophilic aerosol is usually lower than 27.6 h over the entire landmass and lower than 10 h over the polluted Indo‐Gangetic Basin (IGB), with seasonal variability. Due to the implementation of the dynamic aging scheme, the column burden and surface mass concentration of carbonaceous aerosols increase during the drier season (December–February) when washout is negligible. The burden is reduced during the wet season (June–September) due to a more efficient washout except over the IGB, where a reduction in precipitation as a result of radiative feedbacks increases the aerosol concentrations. Over the polluted IGB, surface dimming increases due to the dynamic aging scheme, with the top of the atmosphere forcing remaining mostly unchanged. As a result, atmospheric heating increases by at least 1.2 W/m2. Our results suggest that climate models should incorporate dynamic aging for a more realistic representation of aerosol simulations, especially in highly polluted regions.
The Impact of Measurement Scale on the Univariate Statistics of K, Th, and U in the Earth Crust
Authors: Baratoux D. , Fall M. , Meslin P.‐Y. , Jessell M. W. , Vanderhaeghe O. , Moyen J.‐F. , Ndiaye P. M. , Boamah K. , Baratoux L. , André‐Mayer A.‐S.
Published: August 2021

The univariate statistics of Potassium (K), thorium (Th), and uranium (U) concentrations, in the Earth’s oceanic and continental crust are examined by different techniques. The frequency distributions of the concentrations of these elements in the oceanic crust are derived from a global catalog of mid‐ocean ridge basalts. Their frequency distributions of concentrations in the continental crust are illustrated by the North Pilbara Craton, and the West Africa Craton. For these two cratons, the distributions of K, Th, and U derived from geochemical analyses of several thousand whole rock samples differ significantly from those derived from airborne radiometric surveys. The distributions from airborne surveys tends to be more symmetric with smaller standard deviations than the right‐skewed distributions inferred from whole rock geochemical analyses. Hypothetic causes of these differences include (a) bias in rock sampling or in airborne surveys, (b) the differences between the chemistry of superficial material and rocks, and (c) the differences in scales of measurements. The scale factor, viewed as consequence of the central limit theorem applied to K, Th, and U concentrations, appears to account for most of the observed differences in the distributions of K, Th, and U. It suggests that the three scales of auto‐correlation of K, Th, and U concentrations are of the same order of magnitude as the resolution of the airborne radiometric surveys (50–200 m). Concentrations of K, Th, and U are therefore generally heterogenous at smaller scales.
Using CloudSat‐Derived Snow Accumulation Estimates to Constrain Gridded Snow Water Equivalent Products
Authors: King Fraser , Fletcher Christopher G.
Published: August 2021

Changes in the quantity of terrestrial Arctic snow have far‐reaching implications for the global water‐energy budget, ecosystem development, and cold region flooding. Snow water equivalent (SWE) is a useful metric for monitoring these changes, however only a sparse observing network is available in the Arctic. Space‐based remote sensing offers the potential to fill these measurement gaps, and the CloudSat cloud profiling radar (CPR) has been shown to provide high‐quality estimates of surface snowfall rates across the Arctic. We propose a novel method to leverage monthly information from CloudSat to identify data quality issues in the Blended‐4 (B4) gridded SWE product. A regression of estimated monthly mean snow accumulation between CloudSat and B4 provides a confidence interval to objectively flag individual months in B4 with data quality issues. Applying this method to a case study in the Canadian high Arctic identifies an unphysical January melt event in B4 which is traced back to a measurement error in the assimilated station observations. We generalize this technique to a one‐degree grid and find a total of 4,885 cases in B4 with low data quality. We find that the low‐quality SWE product values are not random errors, and that they introduce a systematic bias of −3.1 mm on B4's estimates of mean Arctic SWE. CloudSat is uniquely positioned as one of the only observational data sets for observing snowfall at high latitudes, and when combined with the methodology developed here, its estimates can be used to further enhance the accuracy of current gridded SWE products.
Indigenous Peoples Harness Space Technology to Stop Deforestation
Authors: Wight Andrew
Published: August 2021

Satellite observations have long been used to detect deforestation, and a new study shows that giving Indigenous groups greater access to these data can improve response times and reduce tree cover loss.
Drought Resilience Debt Drives NPP Decline in the Amazon Forest
Authors: Machado‐Silva Fausto , Peres Leonardo F. , Gouveia Celia M. , Enrich‐Prast Alex , Peixoto Roberta B. , Pereira José M. C. , Marotta Humberto , Fernandes Pedro J. F. , Libonati Renata
Published: August 2021

Climate change has substantially increased the frequency of extreme droughts in the Amazon basin, generating concern about impacts on the world's largest tropical forest, which contributes about one‐seventh of the global vegetation carbon sink. Most research to understand drought impacts has focused on the immediate influences of such events, neglecting post‐drought effects on ecosystems recovery. Since ecological processes are influenced by antecedent conditions, we analyzed whether extreme droughts affect vegetation growth (i.e., net primary productivity, NPP) recovery. Here, we evaluated the NPP in the Amazon basin from 2003 to 2020, a period in which drought frequency was almost double the decadal incidence of the last century. We show that NPP does respond to the coupled impacts of individual droughts and the post‐drought impacts during ecosystem recovery. In particular, our results reveal that the ecosystems undergoing recovery show NPP about 13% lower than reference values based on the pre‐drought state or in areas undisturbed by drought. NPP deficits have consistently increased with the extreme droughts of 2005, 2010, and 2015 due to the combined effects of disturbances magnitude and the length of recovery. If the expected increase in drought frequency and intensity does occur, reduced recovery may lead the Amazon Forest to an alternative ecosystem state with lower carbon uptake, contributing to a warming global climate.
Constraints From Exhumed Rocks on the Seismic Signature of the Deep Subduction Interface
Authors: Tewksbury‐Christle C. M. , Behr W. M.
Published: August 2021

Low Velocity Zones (LVZs) with anomalously high Vp‐Vs ratios occur along the downdip extents of subduction megathrusts in most modern subduction zones and are collocated with complex seismic and transient deformation patterns. LVZs are attributed to high pore fluid pressures, but the spatial correlation between the LVZ and the subduction interface, as well as the rock types that define them, remain unclear. We characterize the seismic signature of a fossil subduction interface shear zone in northern California that is sourced from the same depth range as modern LVZs. Deformation was distributed across 3 km of dominantly metasedimentary rocks, with periodic strain localization to km‐scale ultramafic lenses. We estimate seismic velocities accounting for mineral and fracture anisotropy, constrained by microstructural observations and field measurements, resulting in a Vp/Vs of 2.0. Comparable thicknesses and velocities suggest that LVZs represent, at least in part, the subduction interface shear zone.
A Connection of Winter Eurasian Cold Anomaly to the Modulation of Ural Blocking by ENSO
Authors: Luo Binhe , Luo Dehai , Dai Aiguo , Simmonds Ian , Wu Lixin
Published: August 2021

This study investigates how El Niño‐Southern Oscillation (ENSO) modulates winter cold anomalies over central Eurasia (CE) using reanalysis data during 1950–2019. It is found that ENSO can significantly influence winter air temperature over CE mainly through modulating the strength and location of the cyclonic anomaly of Ural blocking (UB) or long‐lived UB events. A strong (weak) cyclonic anomaly of UB on the southeastern (eastern) side of the Ural Mountains tends to occur over midlatitude (high‐latitude) Eurasia during La Niña (El Niño) winters. Such anomalous circulation leads to a strong (weak) cold anomaly over CE, especially over East Asia, due to enhanced (weakened) cold air advection toward the CE during La Niña (El Niño). The UB‐related cyclonic anomaly in the midlatitude (high latitude) side of Eurasia is shown to be related to weakened (enhanced) eastward extension of strong westerly winds over midlatitude Eurasia during La Niña (El Niño) winters.
Advanced Bulk Optical Models Linking the Backscattering and Microphysical Properties of Mineral Dust Aerosol
Authors: Saito Masanori , Yang Ping
Published: August 2021

Sensitivities of the backscattering properties to the microphysical properties (in particular, size and shape) of mineral dust aerosols are examined based on TAMUdust2020, a comprehensive single‐scattering property database of irregular aerosol particles. We develop the bulk mineral dust particle models based on size‐resolved particle ensembles with randomly distorted shapes and spectrally resolved complex refractive indices, which are constrained by using in situ observations reported in the literature. The light detection and ranging (lidar) ratio is more sensitive to particle shape than particle size, while the depolarization ratio depends strongly on particle size. The simulated bulk backscattering properties (i.e., the lidar ratio and the depolarization ratio) of typical mineral dust particles with effective radii of 0.5–3 µm are reasonably consistent with lidar observations made during several field campaigns. The present dust bulk optical property models are applicable to lidar‐based remote sensing of dust aerosol properties.
Projected Land Evaporation and Its Response to Vegetation Greening Over China Under Multiple Scenarios in the CMIP6 Models
Authors: Lu Jiao , Wang Guojie , Li Shijie , Feng Aiqing , Zhan Mingyue , Jiang Tong , Su Buda , Wang Yanjun
Published: August 2021

Land evaporation (ET) is of great significance in climate change research, water resource management, and numerical weather forecasting. In this study, Ridge Regression Method and Sensitivity Analysis Methods have been used to study the projected land evaporation changes over China, and its response to vegetation greening under low (Shared Socioeconomic Pathway [SSP]1‐2.6), medium (SSP2‐4.5), and high (SSP5‐8.5) forcing scenarios during 2020–2099, based on 16 of the latest generation of Earth System Models (ESMs) taking part in the Coupled Models Intercomparison Project Phase 6. Land evaporation is projected to significantly increase under all climate change scenarios, especially in the southern China where there is a humid climate. The influencing factors, including precipitation, air temperature, solar radiation, and leaf area index (LAI), are analyzed; LAI is indicated to dominate the interannual variations of land ET, contributing over 40% of the interannual variance in the warming climates. However, the sensitivity of land ET to vegetation greening is found to generally reduce along with the increasing radiation forcing levels. Such a reduced sensitivity is particularly true when making intermodel comparisons, possibly due to the uncertainties of vegetation parameterizations in different models. This study reveals the response of land ET to vegetation greening under multiple climate change scenarios, which may help to understand the essential role of vegetation in water cycle and provide support for future water resource management.
Presentation and Evaluation of the IPSL‐CM6A‐LR Ensemble of Extended Historical Simulations
Authors: Bonnet Rémy , Boucher Olivier , Deshayes Julie , Gastineau Guillaume , Hourdin Frédéric , Mignot Juliette , Servonnat Jérôme , Swingedouw Didier
Published: August 2021

The Institut Pierre‐Simon Laplace Climate Modeling Center has produced an ensemble of extended historical simulations using the IPSL‐CM6A‐LR climate model. This ensemble (referred to as IPSL‐EHS) is composed of 32 members over the 1850–2059 period that share the same external forcings but differ in their initial conditions. In this study, we assess the simulated decadal to multidecadal climate variability in the IPSL‐EHS. In particular, we examine the global temperature evolution and recent warming trends, and their consistency with ocean heat content and sea ice cover. The model exhibits a large low‐frequency internal climate variability. In particular, a quasi‐bicentennial mode of internal climate variability is present in the model and is associated with the Atlantic Meridional Overturning Circulation. Such variability modulates the global mean surface air temperature changes over the historical period by about 0.1K. This modulation is found to be linked to the phase present in the initial condition state of each member. This variability appears to decrease during the 1850–2018 period in response to external forcings. The analysis of the ocean heat content reveals furthermore an overestimation of the ocean stratification, which likely leads to an overestimation of the recent warming rate on average.
CXCL12/CXCR4 axis as a key mediator in atrial fibrillation via bioinformatics analysis and functional identification
Authors: Liu Peng , Sun Hongke , Zhou Xin , Wang Qiaozhu , Gao Feng , Fu Yuping , Li Tong , Wang Yixin , Li Yingqi , Fan Boyuan , Li Xiaoli , Jiang Tiannan , Qin Xinghua , Zheng Qiangsun
Published: August 2021

Atrial fibrillation (AF) is an increasingly prevalent arrhythmia with significant health and socioeconomic impact. The underlying mechanism of AF is still not well understood. In this study, we sought to identify hub genes involved in AF, and explored their functions and underlying mechanisms based on bioinformatics analysis. Five microarray datasets in GEO were used to identify the differentially expressed genes (DEGs) by Robust Rank Aggregation (RRA), and hub genes were screened out using protein–protein interaction (PPI) network. AF model was established using a mixture of acetylcholine and calcium chloride (Ach-CaCl2) by tail vein injection. We totally got 35 robust DEGs that mainly involve in extracellular matrix formation, leukocyte transendothelial migration, and chemokine signaling pathway. Among these DEGs, we identified three hub genes involved in AF, of which CXCL12/CXCR4 axis significantly upregulated in AF patients stands out as one of the most potent targets for AF prevention, and its effect on AF pathogenesis and underlying mechanisms were investigated in vivo subsequently with the specific CXCR4 antagonist AMD3100 (6 mg/kg). Our results demonstrated an elevated transcription and translation of CXCL12/CXCR4 axis in AF patients and mice, accompanied with the anabatic atrial inflammation and fibrosis, thereby providing the substrate for AF maintenance. Blocking its signaling via AMD3100 administration in AF model mice reduced AF inducibility and duration, partly ascribed to decreased atrial inflammation and structural remodeling. Mechanistically, these effects were achieved by reducing the recruitment of CD3+ T lymphocytes and F4/80+ macrophages, and suppressing the hyperactivation of ERK1/2 and AKT/mTOR signaling in atria of AF model mice. In conclusion, this study provides new evidence that antagonizing CXCR4 prevents the development of AF, and suggests that CXCL12/CXCR4 axis may be a potential therapeutic target for AF.
Flat epitaxial quasi-1D phosphorene chains
Authors: Zhang Wei , Enriquez Hanna , Tong Yongfeng , Mayne Andrew J. , Bendounan Azzedine , Smogunov Alex , Dappe Yannick J. , Kara Abdelkader , Dujardin Gérald , Oughaddou Hamid
Published: August 2021

The emergence of peculiar phenomena in 1D phosphorene chains (P chains) has been proposed in theoretical studies, notably the Stark and Seebeck effects, room temperature magnetism, and topological phase transitions. Attempts so far to fabricate P chains, using the top-down approach starting from a few layers of bulk black phosphorus, have failed to produce reliably precise control of P chains. We show that molecular beam epitaxy gives a controllable bottom-up approach to grow atomically thin, crystalline 1D flat P chains on a Ag(111) substrate. Scanning tunneling microscopy, angle-resolved photoemission spectroscopy, and density functional theory calculations reveal that the armchair-shaped chains are semiconducting with an intrinsic 1.80 ± 0.20 eV band gap. This could make these P chains an ideal material for opto-electronic devices.
Simultaneous bicolor interrogation in thulium optical clock providing very low systematic frequency shifts
Authors: Golovizin Artem A. , Tregubov Dmitry O. , Fedorova Elena S. , Mishin Denis A. , Provorchenko Daniil I. , Khabarova Ksenia Yu. , Sorokin Vadim N. , Kolachevsky Nikolai N.
Published: August 2021

Optical atomic clocks have already overcome the eighteenth decimal digit of instability and uncertainty, demonstrating incredible control over external perturbations of the clock transition frequency. At the same time, there is an increasing demand for atomic (ionic) transitions and new interrogation and readout protocols providing minimal sensitivity to external fields and possessing practical operational wavelengths. One of the goals is to simplify the clock operation while maintaining the relative uncertainty at a low 10−18 level achieved at the shortest averaging time. This is especially important for transportable and envisioned space-based optical clocks. Here, we demonstrate implementation of a synthetic frequency approach for a thulium optical clock with simultaneous optical interrogation of two clock transitions. Our experiment shows suppression of the quadratic Zeeman shift by at least three orders of magnitude. The effect of the tensor lattice Stark shift in thulium can also be reduced to below 10−18 in fractional frequency units. This makes the thulium optical clock almost free from hard-to-control systematic shifts. The “simultaneous” protocol demonstrates very low sensitivity to the cross-talks between individual clock transitions during interrogation and readout.
CTCF and transcription influence chromatin structure re-configuration after mitosis
Authors: Zhang Haoyue , Lam Jessica , Zhang Di , Lan Yemin , Vermunt Marit W. , Keller Cheryl A. , Giardine Belinda , Hardison Ross C. , Blobel Gerd A.
Published: August 2021

During mitosis, transcription is globally attenuated and chromatin architecture is dramatically reconfigured. We exploited the M- to G1-phase progression to interrogate the contributions of the architectural factor CTCF and the process of transcription to genome re-sculpting in newborn nuclei. Depletion of CTCF during the M- to G1-phase transition alters short-range compartmentalization after mitosis. Chromatin domain boundary re-formation is impaired upon CTCF loss, but a subset of boundaries, characterized by transitions in chromatin states, is established normally. Without CTCF, structural loops fail to form, leading to illegitimate contacts between cis-regulatory elements (CREs). Transient CRE contacts that are normally resolved after telophase persist deeply into G1-phase in CTCF-depleted cells. CTCF loss-associated gains in transcription are often linked to increased, normally illegitimate enhancer-promoter contacts. In contrast, at genes whose expression declines upon CTCF loss, CTCF seems to function as a conventional transcription activator, independent of its architectural role. CTCF-anchored structural loops facilitate formation of CRE loops nested within them, especially those involving weak CREs. Transcription inhibition does not significantly affect global architecture or transcription start site-associated boundaries. However, ongoing transcription contributes considerably to the formation of gene domains, regions of enriched contacts along gene bodies. Notably, gene domains emerge in ana/telophase prior to completion of the first round of transcription, suggesting that epigenetic features in gene bodies contribute to genome reconfiguration prior to transcription. The focus on the de novo formation of nuclear architecture during G1 entry yields insights into the contributions of CTCF and transcription to chromatin architecture dynamics during the mitosis to G1-phase progression.
Deep neural networks using a single neuron: folded-in-time architecture using feedback-modulated delay loops
Authors: Stelzer Florian , Röhm André , Vicente Raul , Fischer Ingo , Yanchuk Serhiy
Published: August 2021

Deep neural networks are among the most widely applied machine learning tools showing outstanding performance in a broad range of tasks. We present a method for folding a deep neural network of arbitrary size into a single neuron with multiple time-delayed feedback loops. This single-neuron deep neural network comprises only a single nonlinearity and appropriately adjusted modulations of the feedback signals. The network states emerge in time as a temporal unfolding of the neuron’s dynamics. By adjusting the feedback-modulation within the loops, we adapt the network’s connection weights. These connection weights are determined via a back-propagation algorithm, where both the delay-induced and local network connections must be taken into account. Our approach can fully represent standard Deep Neural Networks (DNN), encompasses sparse DNNs, and extends the DNN concept toward dynamical systems implementations. The new method, which we call Folded-in-time DNN (Fit-DNN), exhibits promising performance in a set of benchmark tasks.
Stable representation of a naturalistic movie emerges from episodic activity with gain variability
Authors: Xia Ji , Marks Tyler D. , Goard Michael J. , Wessel Ralf
Published: August 2021

Visual cortical responses are known to be highly variable across trials within an experimental session. However, the long-term stability of visual cortical responses is poorly understood. Here using chronic imaging of V1 in mice we show that neural responses to repeated natural movie clips are unstable across weeks. Individual neuronal responses consist of sparse episodic activity which are stable in time but unstable in gain across weeks. Further, we find that the individual episode, instead of neuron, serves as the basic unit of the week-to-week fluctuation. To investigate how population activity encodes the stimulus, we extract a stable one-dimensional representation of the time in the natural movie, using an unsupervised method. Most week-to-week fluctuation is perpendicular to the stimulus encoding direction, thus leaving the stimulus representation largely unaffected. We propose that precise episodic activity with coordinated gain changes are keys to maintain a stable stimulus representation in V1.
Copy number signatures predict chromothripsis and clinical outcomes in newly diagnosed multiple myeloma
Authors: Maclachlan Kylee H. , Rustad Even H. , Derkach Andriy , Zheng-Lin Binbin , Yellapantula Venkata , Diamond Benjamin , Hultcrantz Malin , Ziccheddu Bachisio , Boyle Eileen M. , Blaney Patrick , Bolli Niccolò , Zhang Yanming , Dogan Ahmet , Lesokhin Alexander M. , Morgan Gareth J. , Landgren Ola , Maura Francesco
Published: August 2021

Chromothripsis is detectable in 20–30% of newly diagnosed multiple myeloma (NDMM) patients and is emerging as a new independent adverse prognostic factor. In this study we interrogate 752 NDMM patients using whole genome sequencing (WGS) to investigate the relationship of copy number (CN) signatures to chromothripsis and show they are highly associated. CN signatures are highly predictive of the presence of chromothripsis (AUC = 0.90) and can be used identify its adverse prognostic impact. The ability of CN signatures to predict the presence of chromothripsis is confirmed in a validation series of WGS comprised of 235 hematological cancers (AUC = 0.97) and an independent series of 34 NDMM (AUC = 0.87). We show that CN signatures can also be derived from whole exome data (WES) and using 677 cases from the same series of NDMM, we are able to predict both the presence of chromothripsis (AUC = 0.82) and its adverse prognostic impact. CN signatures constitute a flexible tool to identify the presence of chromothripsis and is applicable to WES and WGS data.
Antipsychotic-placebo separation on the PANSS-6 subscale as compared to the PANSS-30: a pooled participant-level analysis
Authors: Hieronymus Fredrik , Kølbæk Pernille , Correll Christoph U. , Østergaard Søren D.
Published: August 2021

In order for measurement-based care to be implemented, there is a need for brief rating instruments that can be administered in a short amount of time, but that are still sufficiently informative. Here, we assessed the drug–placebo sensitivity of the six-item subscale (PANSS-6) of the 30-item Positive and Negative Syndrome Scale (PANSS-30) using a large collection of patient-level data (n = 6685) from randomized controlled trials of risperidone and paliperidone. When analyzing the data by study, we found no material difference in mean effect sizes (ES) between the two measures (PANSS-30 ES = 0.45, PANSS-6 ES = 0.44; p = 0.642). Stratifying the pooled population according to several putative effect moderators (e.g., age, formulation, dose, or diagnosis) generally yielded no meaningful ES differences between the two measures. Similarly, early improvement (≥20% improvement at week 1) on the PANSS-6 predicted subsequent response (≥40% improvement at endpoint) as well as the analog prediction using PANSS-30. Finally, cross-sectional symptom remission assessed via the PANSS-6 showed very good agreement (sensitivity = 100%, specificity = 98%) with cross-sectional symptom remission defined by the Remission in Schizophrenia Working Group.
Author Correction: Study of mouse behavior in different gravity environments
Authors: Shimomura Michihiko , Yumoto Akane , Ota‑Murakami Naoko , Kudo Takashi , Shirakawa Masaki , Takahashi Satoru , Morita Hironobu , Shiba Dai
Published: August 2021

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Human osteoblast and fibroblast response to oral implant biomaterials functionalized with non-thermal oxygen plasma
Authors: Rabel Kerstin , Kohal Ralf-Joachim , Steinberg Thorsten , Rolauffs Bernd , Adolfsson Erik , Altmann Brigitte
Published: August 2021

Plasma-treatment of oral implant biomaterials prior to clinical insertion is envisaged as a potential surface modification method for enhanced implant healing. To investigate a putative effect of plasma-functionalized implant biomaterials on oral tissue cells, this investigation examined the response of alveolar bone osteoblasts and gingival fibroblasts to clinically established zirconia- and titanium-based implant surfaces for bone and soft tissue integration. The biomaterials were either functionalized with oxygen-plasma in a plasma-cleaner or left untreated as controls, and were characterized in terms of topography and wettability. For the biological evaluation, the cell adhesion, morphogenesis, metabolic activity and proliferation were examined, since these parameters are closely interconnected during cell-biomaterial interaction. The results revealed that plasma-functionalization increased implant surface wettability. The magnitude of this effect thereby depended on surface topography parameters and initial wettability of the biomaterials. Concerning the cell response, plasma-functionalization of smooth surfaces affected initial fibroblast morphogenesis, whereas osteoblast morphology on rough surfaces was mainly influenced by topography. The plasma- and topography-induced differential cell morphologies were however not strong enough to trigger a change in proliferation behaviour. Hence, the results indicate that oxygen plasma-functionalization represents a possible cytocompatible implant surface modification method which can be applied for tailoring implant surface wettability.
Development of multiplex digital PCR assays for the detection of PIK3CA mutations in the plasma of metastatic breast cancer patients
Authors: Corné Julien , Le Du Fanny , Quillien Véronique , Godey Florence , Robert Lucie , Bourien Héloïse , Brunot Angélique , Crouzet Laurence , Perrin Christophe , Lefeuvre-Plesse Claudia , Diéras Véronique , De la Motte Rouge Thibault
Published: August 2021

With the approval of new therapies targeting the PI3K pathway, the detection of PIK3CA mutations has become a key factor in treatment management for HR+/HER2− metastatic breast cancer (MBC). We developed multiplex digital PCR (dPCR) assays to detect and quantify PIK3CA mutations. A first screening assay allows the detection of 21 mutations, with a drop-off system targeting the 542–546 hotspot mutations combined with the simultaneous detection of N345K, C420R, H1047L and H1047R mutations. In the case of a positive result, a sequential strategy based on other assays that we have developped allows for precise mutation identification. Clinical validity was determined by analyzing plasma circulating free DNA (cfDNA) from 213 HR+/HER2− MBC samples, as well as DNA extracted from 97 available matched tumors from 89 patients. Our assays have shown reliable specificity, accuracy and reproducibility, with limits of blank of three and four droplets for the screening assay. Sixty-eight patients (32%) had at least one PIK3CA mutation detectable in their plasma, and we obtained 83.1% agreement between the cfDNA analysis and the corresponding tumors. The high sensitivity and robustness of these new dPCR assays make them well-suited for rapid and cost-effective detection of PIK3CA mutations in the plasma of MBC patients.
Mobilization of progenitor cells and vessel healing after implantation of SYNERGY in acute coronary syndrome
Authors: Sakuma Masashi , Nishino Setsu , Nasuno Takahisa , Kageyama Michiya , Tokura Michiaki , Sohma Ryoichi , Inoue Ken-ichi , Kanaya Tomoaki , Obi Syotaro , Toyoda Shigeru , Abe Shichiro , Attizzani Guiherme F. , Pereira Gabriel T. R. , Bezerra Hiram G. , Inoue Teruo
Published: August 2021

This study was aimed to compare the vascular healing process of a SYNERGY stent with that of a PROMUS PREMIER stent in patients with acute coronary syndrome (ACS). In 71 patients with ACS, undergoing coronary stent implantation using the SYNERGY stent (n = 52) or PROMUS PREMIER stent (n = 19), we measured circulating CD34+/CD133+/CD45null cells and CD34+/KDR+ cells and observed vascular healing at the stented sites using optical coherence tomography (OCT) and coronary angioscopy. On the day 7, circulating CD34+/CD133+/CD45null cells increased in SYNERGY group (P < 0.0001), while it did not change in PROMUS group. The CD34+/KDR+ cells also increased in SYNERGY group (P < 0.0001) but less significantly in the PROMUS group (P < 0.05). The OCT-based neointimal thickness (P < 0.0005) and neointimal coverage rate (P < 0.05) at 12 months were greater in SYNERGY group, compared with PROMUS group. The coronary angioscopy-based neointimal coverage grade at 12 months was also greater in SYNERGY group (P < 0.001). In overall patients, the change in CD34+/KDR+ cells on the day 7 correlated with the OCT-based neointimal thickness at 12 months (R = 0.288, P < 0.05). SYNERGY stent seems to have potential advantages over PROMUS PREMIER stent for ACS patients in terms of vascular healing process at the stented sites.
2000 years of agriculture in the Atacama desert lead to changes in the distribution and concentration of iron in maize
Authors: Vidal Elgueta Ale , Navarro Nathalia , Uribe Mauricio , Robe Kevin , Gaymard Frédéric , Dubos Christian , Pérez María Fernanda , Roschzttardtz Hannetz
Published: August 2021

We performed a histological and quantitative study of iron in archaeological maize seeds from prehispanic times recovered from Tarapacá, Atacama Desert. Also, we examined iron distribution changes at the cell level in embryos from ancient versus new varieties of maize. Our results show a progressive decrease in iron concentration from the oldest maize to modern specimens. We interpret the results as an effect of prehispanic agriculture over the micronutrient composition of maize.
An analysis of frailty and multimorbidity in 20,566 UK Biobank participants with type 2 diabetes
Authors: Hanlon Peter , Jani Bhautesh D. , Butterly Elaine , Nicholl Barbara , Lewsey Jim , McAllister David A. , Mair Frances S.
Published: August 2021

Background

Frailty and multimorbidity are common in type 2 diabetes (T2D), including people <65 years. Guidelines recommend adjustment of treatment targets in people with frailty or multimorbidity. It is unclear how recommendations to adjust treatment targets in people with frailty or multimorbidity should be applied to different ages. We assess implications of frailty/multimorbidity in middle/older-aged people with T2D.

Methods

We analysed UK Biobank participants (n = 20,566) with T2D aged 40–72 years comparing two frailty measures (Fried frailty phenotype and Rockwood frailty index) and two multimorbidity measures (Charlson Comorbidity index and count of long-term conditions (LTCs)). Outcomes were mortality, Major Adverse Cardiovascular Event (MACE), hospitalization with hypoglycaemia or fall/fracture.

Results

Here we show  that choice of measure influences the population identified: 42% of participants are frail or multimorbid by at least one measure; 2.2% by all four measures. Each measure is associated with mortality, MACE, hypoglycaemia, and fall or fracture. The absolute 5-year mortality risk is higher in older versus younger participants with a given level of frailty (e.g. 1.9%, and 9.9% in men aged 45 and 65, respectively, using frailty phenotype) or multimorbidity (e.g. 1.3%, and 7.8% in men with 4 LTCs aged 45 and 65, respectively). Using frailty phenotype, the relationship between higher HbA1c and mortality is stronger in frail compared with pre-frail or robust participants.

Conclusions

Assessment of frailty/multimorbidity should be embedded within routine management of middle-aged and older people with T2D. Method of identification as well as features such as age impact baseline risk and should influence clinical decisions (e.g. glycaemic control).
Enzyme-responsive micellar JQ1 induces enhanced BET protein inhibition and immunotherapy of malignant tumors
Authors: Zhang Zhenqi , Zhang Qiang , Xie Jiguo , Zhong Zhiyuan , Deng Chao
Published: August 2021

mJQ1 nanodrugs combined with radiotherapy displayed significant immune activation and superb tumor killing ability of both primary and distant tumors.
Self-adjuvanting photosensitizer nanoparticles for combination photodynamic immunotherapy
Authors: Zhang Guiqiang , Wang Ning , Sun Haifeng , Fu Xiao , Zhai Shumei , Cui Jiwei
Published: August 2021

Self-assembled nanoparticles composed of photosensitizers and immune adjuvants are reported for combination photodynamic immunotherapy to inhibit both primary and distant tumors.
Key intermediates from simultaneous removal of NOx and chlorobenzene over a V2O5–WO3/TiO2 catalyst: a combined experimental and DFT study
Authors: Gao Chuan , Yang Guangpeng , Huang Xu , Yang Qilei , Li Bing , Wang Dong , Peng Yue , Li Junhua , Lu Chunmei , Crittenden John
Published: August 2021

Chlorobenzene suppresses the active cis-N2O22− formation and the dissociated Cl− combines with vanadium to form vanadium chloride which enhanced surface Brønsted acidity.
Comparison study of the effect of CeO2-based carrier materials on the total oxidation of CO, methane, and propane over RuO2
Authors: Wang Zheng , Khalid Omeir , Wang Wei , Wang Yu , Weber Tim , Spriewald Luciano Alexander , Zhan Wangcheng , Smarsly Bernd M. , Over Herbert
Published: August 2021

While activity and kinetics of catalytic CO and propane combustion over RuO2depends sensitively on the carrier material, methane combustion on RuO2is hardly affected by the carrier.
Toward improved human health: Nrf2 plays a critical role in regulating ferroptosis
Authors: Lu Jing , Zhao Yanan , Liu Meitong , Lu Jianing , Guan Shuang
Published: August 2021

Toward food function with beneficial effect in regulating ferroptosis via Nrf2 pathway.
High performance sub-bandgap photodetectionviainternal photoemission based on ideal metal/2D-material van der Waals Schottky interface
Authors: Li Xuhong , Chen Xiaoqing , Li Songyu , Chu Feihong , Deng Wenjie , Zhang Xiaobo , Li Jingjie , Bao Xiulong , An Boxing , You Congya , Liu Famin , Zhang Yongzhe
Published: August 2021

A special laminating-flipping technique was introduced, which realized a sub-bandgap responsivity based on the internal photoemission of the ideal van der Waals Schottky interface.
Mechanistic investigation of redox processes in Zn–MnO2 battery in mild aqueous electrolytes
Authors: Rodríguez-Pérez Ismael A. , Chang Hee Jung , Fayette Matthew , Sivakumar Bhuvaneswari M. , Choi Daiwon , Li Xiaolin , Reed David
Published: August 2021

We present a deep fundamental understanding of the electrolytic manganese dioxide cathode energy storage mechanism using a series of advanced characterization techniques.
Directional solution transfer of a 3D solar evaporator inhibiting salt crystallization
Authors: Peng Ye , Zhao Xinzhen , Liu Changkun
Published: August 2021

A solar evaporator with a special structure has the characteristics of reducing heat loss and recovering energy from the environment. Under the action of directional solution transfer, the effective inhibition of salt crystallization is realized.
Promoting water splitting on arrayed molybdenum carbide nanosheets with electronic modulation
Authors: Diao Jinxiang , Li Xiaolin , Wang Shuya , Zhao Zejun , Wang Weitao , Chen Kai , Chen Xiaoting , Chao Tingting , Yang Yong
Published: August 2021

A facile strategy for the N-induced electronic-structure reformation of the molybdenum carbide nanosheet array material has been developed. This electrocatalyst showed superior activity and stability for water splitting.
Verhaltensaktivierung bei schweren depressiven Störungen: Klinische Prinzipien und Techniken
Authors: Sankin Lindsey S. , Solomonov Nili
Published: August 2021

Verhaltensaktivierung (Behavioral Activation) ist eine kurze, manualisierte, evidenzbasierte Therapie für depressive Störungen. Ihre Prinzipien basieren auf der Verhaltenstherapie. Manualisierte Verhaltensaktivierungs-Therapien wurden Ende der 1990er-Jahre entwickelt und verbreiteten sich in den frühen 2000er-Jahren 1, 2, 3.
Chronische Einsamkeit – mehr als ein Symptom einer Depression
Authors: Krieger Tobias , Seewer Noëmi , Skoko Andrej
Published: August 2021

Einsamkeit kann situativ und vorübergehend sein, aber auch langanhaltend und überdauernd. Obwohl Einsamkeitsgefühle oft zusammen mit depressiven Störungen auftreten, sollten sie nicht ausschließlich als ein Symptom einer Depression verstanden werden. Dieser Beitrag befasst sich mit der Definition von Einsamkeit und einem Erklärungsmodell von chronischer Einsamkeit. Abschließend wird auf Interventionen zur Reduktion von Einsamkeit eingegangen.
Diagnostik und Therapie einer Anti-CD36-induzierten neonatalen Alloimmunthrombozytopenie
Authors: Flesch Brigitte K. , Carbol Alexander
Published: August 2021

Mütterliche Antikörper gegen das HPA-1a auf kindlichen Thrombozyten sind der Hauptverursacher einer fetalen oder neonatalen Alloimmunthrombozytopenie (FNAIT). In asiatischen Populationen wurden wiederholt Isoantikörper gegen CD36 als ursächlich im Zusammenhang mit der FNAIT beschrieben, wohingegen in Mitteleuropa die CD36-Defizienz und damit die Möglichkeit einer Immunisierung praktisch unbekannt sind. Das erschwert deutlich die Transfusion mit kompatiblen Thrombozyten bei FNAIT-Fällen, z. B. bei Neugeborenen asiatischer Abstammung. Bei einem Neugeborenen arabischstämmiger Eltern wurde eine Anti-CD36-induzierte FNAIT diagnostiziert. Die Thrombozytenwerte konnten erfolgreich durch die Gabe HPA-unausgewählter Apheresethrombozytenkonzentrate (ATK) stabilisiert werden. Durch ein vorangegangenes Forschungsprojekt zum CD36-Screening bei Blutspendern arabischer Herkunft stand zusätzlich kurz darauf ein ATK mit sehr schwacher CD36-Expression zur Verfügung, das aber nicht mehr benötigt wurde. Dieser Fall weist somit alternative Therapiemöglichkeiten bei einer Anti-CD36-induzierten FNAIT auf.
Sozialmedizinische Nachsorge bei Frühgeborenen – Auswirkungen des G-BA Beschlusses zur Qualitätssicherungs-Richtlinie Früh- und Reifgeborener (QFR-RL)
Authors: Weishaupt Eva , Reimann Margarete , Hinzpeter Birte , Grimm Marita , Podeswik Andreas , Felderhoff-Müser Ursula , Maria Hüning Britta
Published: August 2021

Hintergrund Fortschritte in der perinatalen Versorgung haben zu einer Senkung der Mortalität sehr unreifer Frühgeborener (FG) geführt bei gleichzeitig unveränderter Langzeit-Morbidität. Die Sozialmedizinische Nachsorge (SMN) ist eine interdisziplinäre Begleitung der Familien zur Sicherstellung des Behandlungserfolges, Verkürzung des stationären Aufenthaltes und Vermeidung von Wiederaufnahmen. Der G-BA fordert in der Qualitätssicherungs-Richtlinie (QFR-RL) u. a. die Sicherstellung der ambulanten Versorgung.

Fragestellung Die vorliegende Studie untersuchte, inwieweit Effekte durch die Umsetzung des G-BA Beschlusses bei den Leistungserbringern wahrgenommen wurden.

Methodik Es wurde eine explorative Umfrage in 101 Einrichtungen durchgeführt, die SMN nach §43 Abs. 2 SGB V anbieten. Die Fallzahlen wurden mit den Daten aus dem Wirkungsbericht des Bundesverbandes Bunter Kreis e.V. und der Neonatalerhebung des IQTIG verglichen.

Ergebnisse Es wurden 53 (52,4%) Datensätze von Teilnehmern aus 9 Bundesländern ausgewertet. 56,6% nehmen Effekte in der Praxis war. Es wurden neue Einrichtungen etabliert (24,5%, n=13), mehr Personal angestellt (17%, n=9) und mehr FG versorgt (18,9%, n=10). Die Fallzahlen zeigen in 2017 eine Versorgungsquote von 24%.

Schlussfolgerung Mehr als die Hälfte der Teilnehmer nehmen Effekte durch die Umsetzung der QFR-RL wahr. Im Gegensatz dazu zeigt sich statistisch kein Unterschied auf Bundesebene in den Fallzahlen für 2016/2017. Eine auskömmliche Finanzierung sowie eine Versorgung müssen flächendeckend zur Umsetzung der QFR-RL realisiert werden.