bluuebunny/crossref_metadata_2025 huggingface dataset:
An evaluation of a group-based cognitive behavioural therapy intervention for low self-esteem
Authors: Swartzman Samantha , Kerr Jenny , McElhinney Rowena
Published: March 2021

Background:

Self-esteem is a common factor in many mental health problems, including anxiety and depression. A cognitive behavioural therapy (CBT)-based protocol called ‘Overcoming Low Self-Esteem’ is available; the use of this protocol in a group format has been associated with improvements in self-esteem. However, it is unclear whether improvements persist after the end of a group-based version of this programme.

Aims:

We aimed to assess whether changes in self-esteem, anxiety and depression persist 3 months after the end of a group version of the Overcoming Low Self-Esteem programme.

Method:

Using data from the National Health Service in Fife, Scotland, we analysed whether there were improvements on self-report measures of self-esteem, anxiety and depression from the beginning of the group to the end of the group and at a follow-up session 3 months later.

Results:

Significant improvements in self-esteem, anxiety and depression are maintained at 3 months follow-up.

Conclusions:

The Overcoming Low Self-Esteem group seems to be associated with improved self-esteem, anxiety and depression. However, further research from randomised controlled trials is needed to establish a causal link between the programme and improved psychological outcomes.
The implementation of the nationwide out-of-hours phone number 1733 in Belgium: analysis of efficiency and safety
Authors: Schoenmakers Birgitte , Delmeiren Lukas , Pietermans Sjors , Janssens Marco , Van Der Mullen Chris , Sabbe Marc
Published: March 2021

Background:

Belgium has a problem with inappropriate use of emergency services. The government installed the number 1733 for out-of-hours care. Through a dry run test, we learned that 30% of all calls were allocated to the protocol ‘unclear problem’. In only 11.9% of all cases, there was an unclear problem.

Methods:

The study aimed to determine whether the adjusted protocol ‘unwell for no clear reason’ led to a safer and more efficient referral and to evaluate the efficiency and safety of the primary care protocols (PCPs). The study ran in cross-sectional design involving patients, General Practitioner Cooperatives and telephone operators. A random sample of calls to 1733 and patient referrals were assessed on efficiency and safety.

Results:

During 6 months in 2018, 11 622 calls to 1733 were registered. Seven hundred fifty-six of them were allocated to ‘unwell for no clear reason’, and a random sample of 180 calls was audited. To evaluate the PCPs, 202 calls were audited. The efficiency and safety of the protocol ‘unwell for no clear reason’ improved, and safety levels for under- and over-triage were not exceeded. The GP’s judged that 9/10 of all patient encounters were correctly referred.

Conclusion:

This study demonstrated that the 1733-telephone triage system for out-of-hours care is successful if protocols, flow charts and emergency levels are well defined, monitored and operators are trained.
The Law and Norms of the European Central Bank as Sovereign Lender of Last Resort: Crystallising Endogenous Authority
Authors: Quinn David
Published: March 2021

Authority of the European Central Bank (the Bank) over its operational norms in the eyes of market actors – Exogenous and endogenous authority and legitimacy – The reconciliation by the Bank and the Court of Justice of the EU (the Court) of the pre-existing norm and political-economic reality with Article 123 TFEU – Sovereign lender of last resort – Eurozone Crisis – Outright Monetary Transactions (OMT) – Public Sector Purchase Programme (PSPP) – Pandemic Emergency Purchase Programme (PEPP)
Elektrokonvulsionstherapie im Kindes- und Jugendalter
Authors: Methfessel Isabel , Weirich Steffen , Rothermel Boris , Crozier Jesse , Besse Matthias , Reinhardt Martin , Buchmann Johannes , Dück Alexander , Zilles-Wegner David , Häßler Frank , Kölch Michael , von Sandersleben Henrik Uebel , Poustka Luise , Sartorius Alexander
Published: March 2021

Zusammenfassung. Hintergrund und Zielsetzung: Die Elektrokonvulsionstherapie (EKT) ist ein hoch wirksames und in der Erwachsenenpsychiatrie gut untersuchtes Therapieverfahren, das gerade bei schwerwiegenden depressiven und psychotischen Erkrankungen erfolgreich eingesetzt wird. Obwohl schwere Krankheitsverläufe auch im kinder- und jugendpsychiatrischen Bereich vorkommen, erfolgt ein Einsatz der EKT hier deutlich seltener. Dies liegt womöglich auch daran, dass kaum systematisch erhobene Daten zur Anwendung, Wirksamkeit und Verträglichkeit der EKT bei kinder- und jugendpsychiatrischen Patient_innen existieren. Ziel dieser Arbeit ist die Untersuchung und Darstellung von Krankheitsverläufen unter EKT-Behandlung im kinder- und jugendpsychiatrischen Bereich und damit eine Vergrößerung der bestehenden Datenbasis zu diesem Thema. Methoden: Es erfolgte eine retrospektive Erhebung zur EKT bei unter 18-jährigen Patient_innen an drei deutschen universitären Zentren. Hier wurden alle dokumentierten Fälle erfasst und auf Wirksamkeit und Verträglichkeit hin untersucht. Darüber hinaus erfolgte eine umfassende PubMed-basierte Datenbankrecherche. Ergebnisse und Schlussfolgerungen: International existieren keine Meta-Analysen oder kontrollierte randomisierte Studien und aus Deutschland kaum veröffentlichte Fälle zum Thema Elektrokonvulsionstherapie in der Kinder- und Jugendpsychiatrie. Unsere Daten zur EKT bei 29 12- bis 17-jährigen Patient_innen zeigen eine gute Wirksamkeit. Nebenwirkungen traten selten auf. Es ergaben sich keine Hinweise auf Unterschiede bezüglich Indikation (Depression, Katatonie, Schizophrenie), Wirksamkeit, negative Prädiktoren und Verträglichkeit einer EKT zwischen erwachsenen und minderjährigen Patient_innen. Die Ergebnisse deuten zudem darauf hin, dass der Einsatz der EKT bei Adoleszenten früher im therapeutischen Prozess in Erwägung gezogen werden sollte.
Tidal Variations in the Mesosphere and Lower Thermosphere Before, During, and After the 2009 Sudden Stratospheric Warming
Authors: Liu Guiping , Lieberman Ruth S. , Harvey V. Lynn , Pedatella Nicholas M. , Oberheide Jens , Hibbins Robert E. , Espy Patrick J. , Janches Diego
Published: March 2021

This work presents a comprehensive evaluation of tides in the mesosphere and lower thermosphere (MLT) of the Whole Atmosphere Community Climate Model with thermosphere‐ionosphere eXtension (WACCMX) and data assimilation provided by the Data Assimilation Research Testbed (DART) ensemble Kalman filter. A total of 26 diurnal and semidiurnal tidal components are calculated using the latest hourly data assimilation cycling during January 12–March 15, 2009 time period. When averaged over this entire yaw cycle, most tidal components display a latitudinal and vertical structures similar to that observed by the Sounding of the Atmosphere using Broadband Emission Radiometry (SABER). However, WACCMX + DART amplitudes of some diurnal tidal components are a factor of ∼1.2–2 times smaller and the peak altitudes and latitudes are shifted compared to SABER. The amplitudes of semidiurnal tides are likewise underestimated in the model, as well as being shifted in altitude and latitude, and some wavenumbers are not captured. Daily tidal variations are calculated in the model and compared with SABER and Super Dual Auroral Radar Network (SuperDARN) radar observations. Both the model and the radars show an amplification of the migrating semidiurnal tide during the week following the peak SSW. Enhancements in nonmigrating diurnal tides are also shown around the SSW peak, which could be produced by the nonlinear interaction between migrating tides and planetary waves. This study finds that, despite using data assimilation to constrain model dynamics, more work is needed in order to accurately simulate the full tidal spectrum and responses to SSWs in the MLT region.
3D Local Earthquake Tomography of the Ecuadorian Margin in the Source Area of the 2016 Mw 7.8 Pedernales Earthquake
Authors: León‐Ríos Sergio , Bie Lidong , Agurto‐Detzel Hans , Rietbrock Andreas , Galve Audrey , Alvarado Alexandra , Beck Susan , Charvis Philippe , Font Yvonne , Hidalgo Silvana , Hoskins Mariah , Laigle Mireille , Oregioni Davide , Meltzer Anne , Ruiz Mario , Woollam Jack
Published: March 2021

Based on manually analyzed waveforms recorded by the permanent Ecuadorian network and our large aftershock deployment installed after the Pedernales earthquake, we derive three‐dimensional Vp and Vp/Vs structures and earthquake locations for central coastal Ecuador using local earthquake tomography. Images highlight the features in the subducting and overriding plates down to 35 km depth. Vp anomalies (∼4.5–7.5 km/s) show the roughness of the incoming oceanic crust (OC). Vp/Vs varies from ∼1.75 to ∼1.94, averaging a value of 1.82 consistent with terranes of oceanic nature. We identify a low Vp (∼5.5 km/s) region extending along strike, in the marine forearc. To the North, we relate this low Vp and Vp/Vs (<1.80) region to a subducted seamount that might be part of the Carnegie Ridge (CR). To the South, the low Vp region is associated with high Vp/Vs (>1.85) which we interpret as deeply fractured, probably hydrated OC caused by the CR being subducted. These features play an important role in controlling the seismic behavior of the margin. While subducted seamounts might contribute to the nucleation of intermediate megathrust earthquakes in the northern segment, the CR seems to be the main feature controlling the seismicity in the region by promoting creeping and slow slip events offshore that can be linked to the updip limit of large megathrust earthquakes in the northern segment and the absence of them in the southern region over the instrumental period.
Methodological Reconstruction of Historical Seismic Events From Anecdotal Accounts of Destructive Tsunamis: A Case Study for the Great 1852 Banda Arc Mega‐Thrust Earthquake and Tsunami
Authors: Ringer H. , Whitehead J. P. , Krometis J. , Harris R. A. , Glatt‐Holtz N. , Giddens S. , Ashcraft C. , Carver G. , Robertson A. , Harward M. , Fullwood J. , Lightheart K. , Hilton R. , Avery A. , Kesler C. , Morrise M. , Klein M. H.
Published: March 2021

We demonstrate the efficacy of a Bayesian statistical inversion framework for reconstructing the likely characteristics of large pre‐instrumentation earthquakes from historical records of tsunami observations. Our framework is designed and implemented for the estimation of the location and magnitude of seismic events from anecdotal accounts of tsunamis including shoreline wave arrival times, heights, and inundation lengths over a variety of spatially separated observation locations. The primary advantage of this approach is that all of the assumptions made in the inversion process are incorporated explicitly into the mathematical framework. As an initial test case we use our framework to reconstruct the great 1852 earthquake and tsunami of eastern Indonesia. Relying on the assumption that these observations were produced by a subducting thrust event, the posterior distribution indicates that the observables were the result of a massive mega‐thrust event with magnitude near 8.8 Mw and a likely rupture zone in the north‐eastern Banda arc. The distribution of predicted epicentral locations overlaps with the largest major seismic gap in the region as indicated by instrumentally recorded seismic events. These results provide a geologic and seismic context for hazard risk assessment in coastal communities experiencing growing population and urbanization in Indonesia. In addition, the methodology demonstrated here highlights the potential for applying a Bayesian approach to enhance understanding of the seismic history of other subduction zones around the world.
Distinct Mineralogy and Age of Individual Lava Flows in Atla Regio, Venus Derived From Magellan Radar Emissivity
Authors: Brossier J. , Gilmore M. S. , Toner K. , Stein A. J.
Published: March 2021

NASA's Magellan mission revealed that many Venus highlands exhibit low radar emissivity values at higher altitudes. This phenomenon is ascribed to the presence of minerals having high dielectric constants, produced or stabilized by temperature‐dependent chemical weathering between the rocks and the atmosphere. Some large volcanoes on Venus have multiple reductions of radar emissivity at varying altitudes. The authors present morphological maps of major lava flow units at Maat, Ozza, and Sapas montes and compare them to radar emissivity. Sapas has a single reduction in emissivity values at 6,054.6 km, while Maat and Ozza have several reductions at altitudes of 6,052.5–6,056.7 km. Emissivity values are highly spatially correlated to individual lava flows indicating that minerals in the rocks control the emissivity signature. The emissivity patterns at these volcanoes require at least four individual ferroelectric mineral compositions in the rocks that are highly conductive at Curie temperatures of 693–731 K. These temperatures are compatible with chlorapatite and some perovskite oxides. Modeling the minimum volumes of ferroelectrics (10–100s ppm) shows the volume and type of ferroelectric may vary over the lifetime of a single volcano. The modeled volumes of ferroelectrics in Ozza and Sapas are greater than in Maat, consistent with the production of ferroelectrics via weathering over a longer period of time, and supporting the idea that Maat has younger volcanic activity. The stratigraphic relationship of Maat's youngest flows with impact craters may indicate the timeframe of the production of specific ferroelectrics via chemical weathering is over 9–60 Ma.
Can Land Surface Models Capture the Observed Soil Moisture Control of Water and Carbon Fluxes in Temperate‐To‐Boreal Forests?
Authors: dos Santos T. , Keppel‐Aleks G. , De Roo R. , Steiner A. L.
Published: March 2021

The reservoir of soil water is exchanged with the atmosphere through evaporative processes, which are mediated via vegetation through transpiration. Carbon uptake is closely coupled to transpiration, and most process‐based models link transpiration and photosynthesis explicitly. Here, we evaluate the simulation of water and carbon fluxes in forested areas of North America using point‐based simulations of the Community Land Model version 5 (CLM5) with Soil Moisture Active/Passive (SMAP) satellite derived soil moisture measurements and in situ measurements at eight Fluxnet and two United States Climate Research Network (CRN) sites. Compared to observations, there is a broad site‐to‐site variability in simulated soil moisture, with some sites exhibiting wet biases and others dry biases. The bias sign does not depend on ecosystem or other environmental drivers such as radiation and temperature. Compared to Fluxnet latent heat (LH) and gross primary production (GPP) flux tower observations, simulated LH flux biases at deciduous broadleaf forests are linked with soil moisture biases, and the model captures the observed seasonal cycle and parabolic seasonal relationship with soil moisture. The parabolic shape is driven by high soil moisture and low LH fluxes in June, peak LH and drier soil conditions in July, followed by further soil moisture drawdown in August. GPP is underestimated at most sites, and the model exhibits a linear relationship between soil moisture and GPP. Because the photosynthesis parameterizations are similar in most Earth system models, further model development that incorporates observations and observed relationships is needed to accurately capture the GPP‐soil moisture relationship.
Comment on “Paleomagnetism of the Late Cretaceous Red Beds From the Far Western Lhasa Terrane: Inclination Discrepancy and Tectonic Implications” by Bian et al.
Authors: Zhao Qian , Huang Baochun , Tao Wei
Published: March 2021

Bian et al. (2020, https://doi.org/10.1029/2020TC006280) recently studied the paleomagnetism of the Late Cretaceous redbeds and summarized all the published paleomagnetic data obtained from the Lhasa terrane. A total of 25 poles from western and central‐eastern Lhasa terrane were collectively analyzed, of which they concluded 21 poles are reliable. These filtered directions, corrected for tilt and depositional biases following Tong et al. (2019, https://doi.org/10.1016/j.earscirev.2019.02.009), were then used to reconstruct the paleoposition and shape of the southern margin of the Asian continent. However, some of Bian et al.'s (2020, https://doi.org/10.1029/2020TC006280) interpretations are in conflict with the known geology of the Lhasa terrane. We argue that they have not applied the appropriate structural corrections to their data. The magnetic directions need to be corrected for a plunging fold axis and evaluated more thoroughly for post‐depositional strain. We recommend the data as presented in Bian et al. (2020, https://doi.org/10.1029/2020TC006280) should not be used for paleogeographic reconstructions. Moreover, cautions need to be given when applying paleomagnetic data with anisotropy of magnetic susceptibility analysis showing pencil structure to the deformational fabric to paleogeographic reconstructions.
Sex-specific genetic architecture in response to American and ketogenic diets
Authors: Salvador Anna C. , Arends Danny , Barrington William T. , Elsaadi Ahmed M. , Brockmann Gudrun A. , Threadgill David W.
Published: March 2021

Background/objectives

There is a growing appreciation for individual responses to diet. In a previous study, mouse strain-specific responses to American and ketogenic diets were observed. In this study, we searched for genetic variants underlying differences in the responses to American and ketogenic diets between C57BL/6J (B6) and FVB/NJ (FVB) mouse strains.

Results

Genetic mapping of fat and lean mass gain revealed QTLs on Chromosome (Chr) 1 at 191.6 Mb (Fmgq1) (P < 0.001, CI = 180.2–194.4 Mb), Chr5 at 73.7 Mb (Fmgq2, Lmgq1) (P < 0.001, CI = 66.1–76.6 Mb), and Chr7 at 40.5 Mb (Fmgq3) (P < 0.01, CI = 36.6–44.5 Mb). Analysis of serum HDL cholesterol concentration identified a significant (P < 0.001, CI = 160.6–176.1 Mb) QTL on Chr1 at 168.6 Mb (Hdlq1). Causal network inference suggests that HDL cholesterol and fat mass gain are both linked to Fmgq1.

Conclusions

Strong sex effects were identified at both Fmgq2 and Lmgq1, which are also diet-dependent. Interestingly, Fmgq2 and Fmgq3 affect fat gain directly, while Fmgq1 influences fat gain directly and via an intermediate change in serum cholesterol. These results demonstrate how precision nutrition will be advanced through the integration of genetic variation and sex in physiological responses to diets varied in carbohydrate composition.
Hepatic sinusoidal obstruction syndrome and short-term application of 6-thioguanine in pediatric acute lymphoblastic leukemia
Authors: Stanulla Martin , Schaeffeler Elke , Möricke Anja , Buchmann Swantje , Zimmermann Martin , Igel Svitlana , Schmiegelow Kjeld , Flotho Christian , Hartmann Hans , Illsinger Sabine , Sauerbrey Axel , Junk Stefanie V. , Schütte Peter , Hinze Laura , Lauten Melchior , Modlich Simon , Kolb Reinhard , Rossig Claudia , Schwabe Georg , Gnekow Astrid K. , Fleischhack Gudrun , Schlegel Paul Gerhard , Schünemann Holger J. , Kratz Christian P. , Cario Gunnar , Schrappe Martin , Schwab Matthias
Published: March 2021

Long-term treatment with 6-thioguanine (6-TG) for pediatric acute lymphoblastic leukemia (ALL) is associated with high rates of hepatic sinusoidal obstruction syndrome (SOS). Nevertheless, current treatment continues to use short-term applications of 6-TG with only sparse information on toxicity. 6-TG is metabolized by thiopurine methyltransferase (TPMT) which underlies clinically relevant genetic polymorphism. We analyzed the association between hepatic SOS reported as a serious adverse event (SAE) and short-term 6-TG application in 3983 pediatric ALL patients treated on trial AIEOP-BFM ALL 2000 (derivation cohort) and defined the role of TPMT genotype in this relationship. We identified 17 patients (0.43%) with hepatic SOS, 13 of which with short-term exposure to 6-TG (P < 0.0001). Eight of the 13 patients were heterozygous for low-activity TPMT variants, resulting in a 22.4-fold (95% confidence interval 7.1–70.7; P ≤ 0.0001) increased risk of hepatic SOS for heterozygotes in comparison to TPMT wild-type patients. Results were supported by independent replication analysis. All patients with hepatic SOS after short-term 6-TG recovered and did not demonstrate residual symptoms. Thus, hepatic SOS is associated with short-term exposure to 6-TG during treatment of pediatric ALL and SOS risk is increased for patients with low-activity TPMT genotypes.
Effects of cancer screening restart strategies after COVID-19 disruption
Authors: Kregting Lindy M. , Kaljouw Sylvia , de Jonge Lucie , Jansen Erik E. L. , Peterse Elisabeth F. P. , Heijnsdijk Eveline A. M. , van Ravesteyn Nicolien T. , Lansdorp-Vogelaar Iris , de Kok Inge M. C. M.
Published: March 2021

Background

Many breast, cervical, and colorectal cancer screening programmes were disrupted due to the COVID-19 pandemic. This study aimed to estimate the effects of five restart strategies after the disruption on required screening capacity and cancer burden.

Methods

Microsimulation models simulated five restart strategies for breast, cervical, and colorectal cancer screening. The models estimated required screening capacity, cancer incidence, and cancer-specific mortality after a disruption of 6 months. The restart strategies varied in whether screens were caught up or not and, if so, immediately or delayed, and whether the upper age limit was increased.

Results

The disruption in screening programmes without catch-up of missed screens led to an increase of 2.0, 0.3, and 2.5 cancer deaths per 100 000 individuals in 10 years in breast, cervical, and colorectal cancer, respectively. Immediately catching-up missed screens minimised the impact of the disruption but required a surge in screening capacity. Delaying screening, but still offering all screening rounds gave the best balance between required capacity, incidence, and mortality.

Conclusions

Strategies with the smallest loss in health effects were also the most burdensome for the screening organisations. Which strategy is preferred depends on the organisation and available capacity in a country.
Achieving clinical success with BET inhibitors as anti-cancer agents
Authors: Shorstova Tatiana , Foulkes William D. , Witcher Michael
Published: March 2021

The transcriptional upregulation of oncogenes is a driving force behind the progression of many tumours. However, until a decade ago, the concept of ‘switching off’ these oncogenic pathways represented a formidable challenge. Research has revealed that members of the bromo- and extra-terminal domain (BET) motif family are key activators of oncogenic networks in a spectrum of cancers; their function depends on their recruitment to chromatin through two bromodomains (BD1 and BD2). The advent of potent inhibitors of BET proteins (BETi), which target either one or both bromodomains, represents an important step towards the goal of suppressing oncogenic networks within tumours. Here, we discuss the biology of BET proteins, advances in BETi design and highlight potential biomarkers predicting their activity. We also outline the logic of incorporating BETi into combination therapies to enhance its efficacy. We suggest that understanding mechanisms of activity, defining predictive biomarkers and identifying potent synergies represents a roadmap for clinical success using BETi.
BMP4 overexpression induces the upregulation of APP/Tau and memory deficits in Alzheimer’s disease
Authors: Zhang Xiaoqing , Li Juan , Ma Li , Xu Hui , Cao Yun , Liang Wei , Ma Jia , Wang Z. Peter , Li Yuyun
Published: March 2021

Alzheimer’s disease (AD) is a chronic progressive degenerative disease of the nervous system. Its pathogenesis is complex and is related to the abnormal expression of the amyloid β (Aβ), APP, and Tau proteins. Evidence has demonstrated that bone morphogenetic protein 4 (BMP4) is highly expressed in transgenic mouse models of AD and that endogenous levels of BMP4 mainly affect hippocampal function. To determine whether BMP4 participates in AD development, transgenic mice were constructed that overexpress BMP4 under the control of the neuron-specific enolase (NSE) promoter. We also performed MTT, FACS, transfection, TUNEL, and Western blotting assays to define the role of BMP4 in cells. We found that middle-aged BMP4 transgenic mice exhibited impaired memory via the Morris water maze experiment. Moreover, their hippocampal tissues exhibited high expression levels of AD-related proteins, including APP, Aβ, PSEN-1, Tau, P-Tau (Thr181), and P-Tau (Thr231). Furthermore, in multiple cell lines, the overexpression of BMP4 increased the expression of AD-related proteins, whereas the downregulation of BMP4 demonstrated opposing effects. Consistent with these results, BMP4 modulation affected cell apoptosis via the regulation of BAX and Bcl-2 expression in cells. Our findings indicate that BMP4 overexpression might be a potential factor to induce AD.
Umbilical cord-derived mesenchymal stromal cells immunomodulate and restore actin dynamics and phagocytosis of LPS-activated microglia via PI3K/Akt/Rho GTPase pathway
Authors: Mukai Takeo , Di Martino Elena , Tsuji Shunichiro , Blomgren Klas , Nagamura-Inoue Tokiko , Ådén Ulrika
Published: March 2021

Microglia are the immune cells in the central nervous system surveying environment and reacting to various injuries. Activated microglia may cause impaired synaptic plasticity, therefore modulating and restoring them to neutral phenotype is crucial to counteract a pro-inflammatory, neurotoxic state. In this study, we focused on elucidating whether human umbilical cord (UC) -derived mesenchymal stromal cells (MSCs) can exert immunomodulatory effect and change the phenotype of activated microglia. Primary culture of microglia was activated by lipopolysaccharide (LPS) and was co-cultured with three lots of MSCs. We investigated immunomodulation, actin dynamics and phagocytic capacity of activated microglia, and examined change of Rho GTPase in microglia as the mechanism. MSCs suppressed the expression of IL-1β and pNFκB in LPS-activated microglia, and conversely elevated the expression of IL-1β in resting-surveying microglia with lot-to-lot variation. Morphological and phagocytotic analyses revealed that LPS stimulation significantly increased active Rho GTPase, Rac1, and Cdc42 levels in the microglia, and their morphology changed to amoeboid in which F-actin spread with ruffle formation. The F-actin spreading persisted after removal of LPS stimulation and reduced phagocytosis. On the other hand, MSC co-culture induced bimodal increase in active Rac1 and Cdc42 levels in LPS-activated microglia. Moreover, extended ruffles of F-actin shrinked and concentrated to form an actin ring, thereby restoring phagocytosis. We confirmed inhibition of the PI3K/Akt pathway attenuated F-actin dynamics and phagocytosis restored by MSCs. Overall, we demonstrated that MSCs immunomodulated microglia with lot-to-lot variation, and changed the phenotype of LPS-activated microglia restoring actin dynamics and phagocytosis by increase of active Rho GTPase.
Role of interleukins in the pathogenesis of pulmonary fibrosis
Authors: She Yi Xin , Yu Qing Yang , Tang Xiao Xiao
Published: March 2021

Interleukins, a group of cytokines participating in inflammation and immune response, are proved to be involved in the formation and development of pulmonary fibrosis. In this article, we reviewed the relationship between interleukins and pulmonary fibrosis from the clinical, animal, as well as cellular levels, and discussed the underlying mechanisms in vivo and in vitro. Despite the effects of interleukin-targeted treatment on experimental pulmonary fibrosis, clinical applications are lacking and unsatisfactory. We conclude that intervening in one type of interleukins with similar functions in IPF may not be enough to stop the development of fibrosis as it involves a complex network of regulation mechanisms. Intervening interleukins combined with other existing therapy or targeting interleukins affecting multiple cells/with different functions at the same time may be one of the future directions. Furthermore, the intervention time is critical as some interleukins play different roles at different stages. Further elucidation on these aspects would provide new perspectives on both the pathogenesis mechanism, as well as the therapeutic strategy and drug development.
Author Correction: Synergetic coordination and catecholamine chemistry for catalytic generation of nitric oxide on vascular stents
Authors: Li Xiangyang , Qiu Hua , Gao Peng , Yang Ying , Yang Zhilu , Huang Nan
Published: March 2021

A Correction to this paper has been published: https://doi.org/10.1038/s41427-021-00293-0
Semi-device-independent random number generation with flexible assumptions
Authors: Pivoluska Matej , Plesch Martin , Farkas Máté , Ružičková Natália , Flegel Clara , Valencia Natalia Herrera , McCutcheon Will , Malik Mehul , Aguilar Edgar A.
Published: March 2021

Our ability to trust that a random number is truly random is essential for fields as diverse as cryptography and fundamental tests of quantum mechanics. Existing solutions both come with drawbacks—device-independent quantum random number generators (QRNGs) are highly impractical and standard semi-device-independent QRNGs are limited to a specific physical implementation and level of trust. Here we propose a framework for semi-device-independent randomness certification, using a source of trusted vacuum in the form of a signal shutter. It employs a flexible set of assumptions and levels of trust, allowing it to be applied in a wide range of physical scenarios involving both quantum and classical entropy sources. We experimentally demonstrate our protocol with a photonic setup and generate secure random bits under three different assumptions with varying degrees of security and resulting data rates.
Stability of filament-wound hyperbolic flexible pipes under internal pressure based on non-geodesic winding
Authors: Xu Guo-min , Shuai Chang-geng
Published: March 2021

Filament-wound flexible pipes are widely used to transport fluid in pipeline systems, proved extremely useful in marine engineering. The hyperbolic flexible pipes have good vibration suppression performance, but they are easily deformed under internal pressure. This paper focuses on the stability of hyperbolic flexible pipes based on the composite Reissner shell theory and the transfer-matrix method. The nonlinear stretch of the reinforced filament and the fiber bridge effect are considered in the model. The calculation results show that a large winding angle reduces the deformation and the meridional stress. The available initial winding angle is limited by the geometry and the slippage coefficient of flexible pipe. The reinforced filament of high tensile modulus will reduce the deformation of the pipe. Compared with the geodesic winding trajectory, non-geodesic winding trajectories improves the stability of the pipe. The theoretical result is verified by the finite element analysis. The investigation method and results present in this paper will guide the design and optimization of more novel flexible pipes in the future.
Non-specific interactions of antibody-oligonucleotide conjugates with living cells
Authors: Lehot Victor , Kuhn Isabelle , Nothisen Marc , Erb Stéphane , Kolodych Sergii , Cianférani Sarah , Chaubet Guilhem , Wagner Alain
Published: March 2021

Antibody-Oligonucleotide Conjugates (AOCs) represent an emerging class of functionalized antibodies that have already been used in a wide variety of applications. While the impact of dye and drug conjugation on antibodies’ ability to bind their target has been extensively studied, little is known about the effect caused by the conjugation of hydrophilic and charged payloads such as oligonucleotides on the functions of an antibody. Previous observations of non-specific interactions of nucleic acids with untargeted cells prompted us to further investigate their impact on AOC binding abilities and cell selectivity. We synthesized a series of single- and double-stranded AOCs, as well as a human serum albumin-oligonucleotide conjugate, and studied their interactions with both targeted and non-targeted living cells using a time-resolved analysis of ligand binding assay. Our results indicate that conjugation of single strand oligonucleotides to proteins induce consistent non-specific interactions with cell surfaces while double strand oligonucleotides have little or no effect, depending on the preparation method.
Novel CARMIL2 loss-of-function variants are associated with pediatric inflammatory bowel disease
Authors: Bosa Luca , Batura Vritika , Colavito Davide , Fiedler Karoline , Gaio Paola , Guo Conghui , Li Qi , Marzollo Antonio , Mescoli Claudia , Nambu Ryusuke , Pan Jie , Perilongo Giorgio , Warner Neil , Zhang Shiqi , Kotlarz Daniel , Klein Christoph , Snapper Scott B. , Walters Thomas D. , Leon Alberta , Griffiths Anne M. , Cananzi Mara , Muise Aleixo M.
Published: March 2021

CARMIL2 is required for CD28-mediated co-stimulation of NF-κB signaling in T cells and its deficiency has been associated with primary immunodeficiency and, recently, very early onset inflammatory bowel disease (IBD). Here we describe the identification of novel biallelicCARMIL2variants in three patients presenting with pediatric-onset IBD and in one with autoimmune polyendocrine syndrome (APS). None manifested overt clinical signs of immunodeficiency before their diagnosis. The first patient presented with very early onset IBD. His brother was found homozygous for the sameCARMIL2null variant and diagnosed with APS. Two other IBD patients were found homozygous for a nonsense and a missenseCARMIL2variant, respectively, and they both experienced a complicated postoperative course marked by severe infections. Immunostaining of bowel biopsies showed reduced CARMIL2 expression in all the three patients with IBD. Western blot and immunofluorescence of transfected cells revealed an altered expression pattern of the missense variant. Our work expands the genotypic and phenotypic spectrum of CARMIL2 deficiency, which can present with either IBD or APS, aside from classic immunodeficiency manifestations.CARMIL2should be included in the diagnostic work-up of patients with suspected monogenic IBD.
Association between denture use, chewing ability, and all-cause mortality in middle-aged and older adults who exercised regularly in Korea
Authors: Jang Jong-Hwa , Kim Ji-Liang , Kim Jae-Hyun
Published: March 2021

Herein, using data from the Korean Longitudinal Study of Aging (2006–2018), we evaluated denture use and chewing ability to determine the status of oral health in middle-aged adults who exercised regularly; further, we investigated the relationship of oral health with all-cause mortality. From the basic survey conducted in 2006, we interviewed 10,254 participants who were followed up until death. The participants were grouped based on regular exercise into REG (n = 3921) and non-REG (n = 6290) groups. The mortality rate was higher in the non-REG group than in the REG group (35.8% versus 26.9%;p < 0.001). The mortality rate was higher in denture users (versus non-denture users), non-drinkers (versus alcohol drinkers), and those on medical aid (versus national health insurance). The mortality rate was higher in participants with poor masticatory ability, lower education level, and poor subjective health perception (p < 0.001). Denture use and masticatory discomfort were not significant risk factors for mortality in the non-REG group (p > 0.05). In conclusion, masticatory discomfort was a risk factor for increased mortality in middle-aged Korean adults who exercised regularly, at least once a week. Thus, assessment of masticatory ability could be a useful indicator of life expectancy in middle-aged adults.
Epidemiology, clinical relevance and prognosis of staphylococci in hospital-acquired postoperative intra-abdominal infections: an observational study in intensive care unit
Authors: Boussion Kévin , Zappella Nathalie , Grall Nathalie , Ribeiro-Parenti Lara , Papin Grégory , Montravers Philippe
Published: March 2021

The pathogenic role of staphylococci in hospital-acquired postoperative intra-abdominal infections (HAIs) has never been evaluated. In a tertiary care university hospital, we assessed the clinical characteristics and outcomes of patients admitted to the intensive care unit for HAIs according to the presence of staphylococci (S-HAI) or their absence (nS-HAI) in peritoneal cultures. Patients with S-HAIs were compared to nS-HAIs patients. Overall, 380 patients were analyzed, including 87 (23%) S-HAI patients [29 Staphylococcus aureus (Sa-HAIs) and 58 coagulase-negative staphylococci (CoNS-HAIs)]. The clinical characteristics did not differ between the S-HAI and nS-HAI patients. Adequacy of empirical anti-infective therapy was achieved less frequently in the staphylococci group (54 vs 72%, respectively, p < 0.01). The 90-day (primary endpoint) and one-year mortality rates did not differ between these groups. The S-HAI patients had decreased rates of postoperative complication (p < 0.05). The adjusted analysis of the clinical outcomes reported a decreased frequency of surgical complications in the staphylococci group (OR 0.43, 95% CI [0.20–0.93], p = 0.03). While the trends toward decreased morbidity criteria were observed in S-HAI patients, the clinical outcomes were not different between the CoNS-HAI and Sa-HAI patients. In summary, our data are not substantial enough to conclude that staphylococci exhibit no pathogenicity in HAIs.
Aspects regarding colour fastness and adsorption studies of a new azo-stilbene dye for acrylic resins
Authors: Popa Simona , Radulescu-Grad Maria Elena , Perdivara Alina , Mosoarca Giannin
Published: March 2021

The aim of this study was the colour fastness investigation of the new synthetized direct symmetrical azo-stilbene dye, using two of the film field domain reference tests, namely the wet-scrub and the UV tests. The dye was incorporated in a water-based resin, and then was applied on a PCV foil. The film colour parameters were determined before and after 200 wet-scrub cycles. Further, the dye was mixed with an acrylo-polyurethanic resin and then was applied on an aluminium plate, which was exposed to UV radiation for 414 h. The film colour parameters were recorded periodically. The maxima of the reflectance spectra depend on the UV time exposure. The quality of the film was analysed by the degree of gloss. A second focus was the elimination of the dye’s traces from wastewaters (these may be resulted from the industries which apply surface coating methods), using the active carbon powder. The main operational adsorption process parameters influence were investigated. Equilibrium, kinetic and thermodynamic studies were performed. The adsorption process was confirmed by the CIEL*a*b* colour space analysis. All colour studies were investigated using UV–Vis spectroscopy.
Author Correction: Statin treatment after acute coronary syndrome: Adherence and reasons for non-adherence in a randomized controlled intervention trial
Authors: Huber Daniel , Wikén Christian , Henriksson Robin , Söderström Lars , Mooe Thomas
Published: March 2021

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Automated severity scoring of atopic dermatitis patients by a deep neural network
Authors: Bang Chul Hwan , Yoon Jae Woong , Ryu Jae Yeon , Chun Jae Heon , Han Ju Hee , Lee Young Bok , Lee Jun Young , Park Young Min , Lee Suk Jun , Lee Ji Hyun
Published: March 2021

Scoring atopic dermatitis (AD) severity with the Eczema Area and Severity Index (EASI) in an objective and reproducible manner is challenging. Automated measurement of erythema, papulation, excoriation, and lichenification severity using images has not yet been investigated. Our aim was to determine whether convolutional neural networks (CNNs) could assess erythema, papulation, excoriation, and lichenification severity at a level of competence comparable to dermatologists. We created a standard dataset of 8,000 clinical images showing AD. Each component of the EASI was scored from 0 to 3 by three dermatologists. We trained four CNNs (ResNet V1, ResNet V2, GoogLeNet, and VGG-Net) with the image dataset and determined which CNN was the most suitable for erythema, papulation, excoriation, and lichenification scoring. The brightness of the images in each dataset was adjusted to − 80% to + 80% of the original brightness (i.e., 9 levels by 20%) to investigate if the CNNs accurately measured scores if image brightness levels were changed. Compared to the dermatologists’ scoring, accuracy rates of the CNNs were 99.17% for erythema, 93.17% for papulation, 96.00% for excoriation, and 97.17% for lichenification. CNNs trained with brightness-adjusted images achieved a high accuracy without the need to standardize camera settings. These results suggested that CNNs perform at level of competence comparable to dermatologists for scoring erythema, papulation, excoriation, and lichenification severity.
Author Correction: Untargeted high-resolution paired mass distance data mining for retrieving general chemical relationships
Authors: Yu Miao , Petrick Lauren
Published: March 2021

A Correction to this paper has been published: https://doi.org/10.1038/s42004-021-00479-1
Common pitfalls and recommendations for using machine learning to detect and prognosticate for COVID-19 using chest radiographs and CT scans
Authors: Roberts Michael , Driggs Derek , Thorpe Matthew , Gilbey Julian , Yeung Michael , Ursprung Stephan , Aviles-Rivero Angelica I. , Etmann Christian , McCague Cathal , Beer Lucian , Weir-McCall Jonathan R. , Teng Zhongzhao , Gkrania-Klotsas Effrossyni ,   AIX-COVNET, Ruggiero Alessandro , Korhonen Anna , Jefferson Emily , Ako Emmanuel , Langs Georg , Gozaliasl Ghassem , Yang Guang , Prosch Helmut , Preller Jacobus , Stanczuk Jan , Tang Jing , Hofmanninger Johannes , Babar Judith , Sánchez Lorena Escudero , Thillai Muhunthan , Gonzalez Paula Martin , Teare Philip , Zhu Xiaoxiang , Patel Mishal , Cafolla Conor , Azadbakht Hojjat , Jacob Joseph , Lowe Josh , Zhang Kang , Bradley Kyle , Wassin Marcel , Holzer Markus , Ji Kangyu , Ortet Maria Delgado , Ai Tao , Walton Nicholas , Lio Pietro , Stranks Samuel , Shadbahr Tolou , Lin Weizhe , Zha Yunfei , Niu Zhangming , Rudd James H. F. , Sala Evis , Schönlieb Carola-Bibiane
Published: March 2021

Machine learning methods offer great promise for fast and accurate detection and prognostication of coronavirus disease 2019 (COVID-19) from standard-of-care chest radiographs (CXR) and chest computed tomography (CT) images. Many articles have been published in 2020 describing new machine learning-based models for both of these tasks, but it is unclear which are of potential clinical utility. In this systematic review, we consider all published papers and preprints, for the period from 1 January 2020 to 3 October 2020, which describe new machine learning models for the diagnosis or prognosis of COVID-19 from CXR or CT images. All manuscripts uploaded to bioRxiv, medRxiv and arXiv along with all entries in EMBASE and MEDLINE in this timeframe are considered. Our search identified 2,212 studies, of which 415 were included after initial screening and, after quality screening, 62 studies were included in this systematic review. Our review finds that none of the models identified are of potential clinical use due to methodological flaws and/or underlying biases. This is a major weakness, given the urgency with which validated COVID-19 models are needed. To address this, we give many recommendations which, if followed, will solve these issues and lead to higher-quality model development and well-documented manuscripts.
Zwitterionic polydopamine coatings suppress silicone implant-induced capsule formation
Authors: Shin Chung Min , Cho Soojeong , Kim Dong Ho , Ha Yooseok , Shin Hyo Jung , Shin Nara , Kim Dong Woon , Choi Chul Hee , Cho Woo Kyung , Oh Sang-Ha
Published: March 2021

This work demonstrates that zwitterionic polydopamine (ZW-DOPA) coating effectively suppressed silicone implant-induced capsule formation through anti-biofilm and anti-fibrotic effects.
Competitive and cooperative n → π* and n → σ* interactions in benzaldehyde–formaldehyde: rotational characterization
Authors: Wang Hao , Wang Juan , Chen Junhua , Herbers Sven , Zheng Huaili , Gou Qian
Published: March 2021

The rotational spectrum of the 1 : 1 benzaldehyde–formaldehyde complex has been investigated by pulsed jet Fourier transform microwave spectroscopy combined with ab initio calculations.
Electrochemical biomass upgrading on CoOOH nanosheets in a hybrid water electrolyzer
Authors: Zhang Ruya , Jiang Shuaihu , Rao Yuan , Chen Shan , Yue Qin , Kang Yijin
Published: March 2021

CoOOH nanosheets synthesized by an in situ electrochemical anion-oxidation strategy were used as anodic catalysts in a hybrid water electrolyzer.
Field-effect pump: liquid dielectrophoresis along a virtual microchannel with source-gate-drain electric fields
Authors: Wang Fu-Min , Lu I-Pei , Lin Chih-Ting , Lu Shey-Shi , Fan Shih-Kang
Published: March 2021

Field-effect pumps (FEPs) driving liquids continuously from source, via gate, toward drain electric fields along a virtual microchannel between parallel plates in linear, transition and saturation regions analogous to field-effect transistors (FETs).
Effects of mixed-valence states of Eu-doped FAPbI3 perovskite crystals studied by first-principles calculation
Authors: Suzuki Atsushi , Oku Takeo
Published: March 2021

Effects of mixed-valence states of europium (Eu)-incorporated CH(NH2)2PbI3 (FAPbI3) and CH3NH3PbI3 (MAPbI3) perovskite crystals on electronic structures were investigated by first-principles calculation.
A site-selective and stereospecific cascade Suzuki–Miyaura annulation of alkyl 1,2-bisboronic esters and 2,2′-dihalo 1,1′-biaryls
Authors: Willems Suzanne , Toupalas Georgios , Reisenbauer Julia C. , Morandi Bill
Published: March 2021

A cascade Suzuki–Miyaura cross-coupling between two non-symmetrical coupling partners gave rise to 9,10-dihydrophenanthrenes with full site-selectivity. The choice of base was critical to facilitate the challenging coupling of the secondary boronate group.
Dual-state efficient chromophore with pH-responsive and solvatofluorochromic properties based on an asymmetric single benzene framework
Authors: Liu Huijing , Zhang Sisi , Ding Liping , Fang Yu
Published: March 2021

An asymmetric single benzene chromophore demonstrates efficient emission in both solution and solid states, and remarkable solvent- and pH-dependent fluorescence, and can be used in visual discrimination of different brands of drinking water.
Intense red emissive organic crystals with elastic bending ability and optical waveguiding behaviour
Authors: Cao Lifu , Tang Baolei , Yu Xu , Ye Kaiqi , Zhang Hongyu
Published: March 2021

Orange (Cry-1O) and red (Cry-1R) emissive crystals were obtained based on a green emissive molecule 1. The light transducing capability of Cry-1R in both the straight and bent states can be applied as an active optical waveguiding medium.
Atomic imaging of the motion and transformation of Pt3Ni nanoparticles in liquids
Authors: Zhang Junyu , Zhao Peng
Published: March 2021

In this work, we used liquid cell TEM to observe the motion and transformation pathways of Pt3Ni nanoparticles in solution by systematically changing the electron beam dose rate.
Ni–Co LDH/M–Mo–S (M = Zn, Co and Ni) nanoarrays as efficient water oxidation electrocatalytic materials
Authors: Wang Haibin , Zhang Xiaoshuang
Published: March 2021

The Ni–Co LDH/Ni–Mo–S catalyst displayed an extraordinary oxygen evolution reaction performance (overpotential of 290 mV at 40 mA cm−2) and a superior durability (retention rate of 90%) at 10 mA cm−2 after 14 h.
On the structure and reactivity of PtnCun (n = 1–7) alloy clusters
Authors: Rodríguez-Kessler Peter L. , Rodríguez-Domínguez Adán R. , Muñoz-Castro Alvaro
Published: March 2021

The structure, electronic and reactivity properties of PtnCun (n = 1–7) clusters are investigated in the framework of density functional theory (DFT).