bluuebunny/crossref_metadata_2025 huggingface dataset:
Retrospective review of the activity and safety of apatinib and anlotinib in patients with advanced osteosarcoma and soft tissue sarcoma
Authors: Tian Zhichao , Liu Huimin , Zhang Fan , Li Liangyu , Du Xinhui , Li Chao , Yang Jinpo , Wang Jiaqiang
Published: February 2020

Background Previous studies have demonstrated the efficacy of apatinib and anlotinib for the treatment of sarcomas. However, more clinical data and evidence are needed to support clinical treatment selection and study design. Here, we evaluated the effectiveness and safety of these two drugs for the treatment of sarcomas. Methods We retrospectively reviewed the data of 110 patients with advanced osteosarcoma (n = 32) or soft tissue sarcoma (STS, n = 78) who received oral apatinib or anlotinib therapy during May 2016–February 2019 at two centers. Patients were divided into the apatinib and anlotinib groups. Results Among osteosarcoma patients, the objective response rates (ORRs) for the apatinib and anlotinib groups were 15.79% (3/19) and 7.69% (1/13), respectively. The disease control rates (DCRs) were 63.16% (12/19) and 30.77% (4/13), and the median progression-free survival (m-PFS) was 4.67 ± 3.01 and 2.67 ± 1.60 months, respectively. Among STS patients, ORRs for the apatinib and anlotinib groups were 12.24% (6/49) and 13.79% (4/29), respectively. The DCRs were 59.18% (29/49) and 55.17% (16/29), and m-PFS was 7.82 ± 6.90 and 6.03 ± 4.50 months, respectively. Regarding adverse events (AEs), apatinib was associated with a higher incidence of hair hypopigmentation and pneumothorax, while anlotinib was associated with a higher incidence of pharyngalgia or hoarseness. Conclusion Both apatinib and anlotinib were effective for the treatment of sarcomas. However, the effectiveness of the two drugs and associated AEs varied based on the histological type of sarcoma. These differences may be due to their different sensitivities to targets such as RET, warranting further study.
Zum Gesundheitsverhalten älterer Beschäftigter – inwieweit stimmen Selbsteinschätzung und Realität überein?
Authors: Borchart Daniela , Hasselhorn Hans Martin , du Prel Jean-Baptist
Published: February 2020

Ziel der Studie

Ältere Beschäftigte sind eine besondere Zielgruppe für die Betriebliche Gesundheitsförderung. Eine realistische Einschätzung des eigenen Gesundheitsverhaltens (EGVh) ist wesentlich für die adäquate Anpassung des Gesundheitsverhaltens (GVh) bei Bedarf. Die EGVh kann nach Sozial- und Gesundheitsaspekten variieren. Daher wird untersucht, wie GVh-Faktoren auf die EGVh älterer Beschäftigter nach soziodemografischen Aspekten und der körperlichen Gesundheit (kGes) wirken.

Methodik

Analysiert wurden die Daten von 3347 älteren Beschäftigten der repräsentativen lidA-Studie 2018. Die EGVh wurde mit der Aussage „Ich tue genug für meine Gesundheit“ erfasst. Als GVh-Faktoren wurden die körperliche Aktivität (kA), der BMI und das Rauchverhalten untersucht. Mit hierarchischen logistischen Regressionen wurde der Einfluss der GVh-Faktoren auf die EGVh kontrolliert für Geschlecht, Alter, Bildung und kGes analysiert. Um das Zusammenspiel der unabhängigen Variablen hinsichtlich der EGVh genauer zu untersuchen, wurde zudem auf Interaktionen getestet.

Ergebnisse

Gesündere Verhaltensweisen sind positiv mit der Zustimmung, genug für die eigene Gesundheit zu tun assoziiert. Allerdings zeigten die gefundenen Interaktionen für bestimmte Personengruppen abweichende Ergebnisse. So stimmen übergewichtige Raucher gegenüber normalgewichtigen mit einer höheren Chance der Aussage zu, genug für die eigene Gesundheit zu tun. Bei Nichtaktiven stieg die Zustimmungschance mit abnehmendem Bildungsniveau.

Schlussfolgerung

Die Identifizierung von Personengruppen, die ihre GVh weniger zutreffend einschätzen als andere, kann helfen, das Angebot an Präventionsmaßnahmen bedürfnisspezifischer zu gestalten. Das Zusammenspiel der Einflussfaktoren auf die EGVh gilt es zukünftig noch genauer zu untersuchen.
Integrating site-specific environmental impact assessment in supplier selection: exemplary application to steel procurement
Authors: Schiessl Andreas , Müller Richard , Volk Rebekka , Zimmer Konrad , Breun Patrick , Schultmann Frank
Published: February 2020

In times of fast-growing stakeholder interest in sustainability, the ecological and social perspective of industrial companies and its products is gaining increasing importance. In particular, the emission of greenhouse gases (GHG) in the automotive industry has come to the forefront of public and governmental attention. The transport sector accounts for 27% of all European GHG emissions and constitutes the largest emitter of CO2e (CO2 equivalents) among all energy demanding technologies. Due to increasingly efficient combustion engines and technology innovation towards e-mobility, the emissions from car manufacturing gain in importance. So far little focus has been laid upon the emissions created throughout the production process in automotive supply chains from a purchasing perspective. The purchasing of raw material from environmentally efficient suppliers can constitute a possibility to significantly reduce CO2e emissions in automotive supply chains and thus contribute to the two degrees global warming goal. Supplier selection decisions, which cover approximately 75% of the value adding process of a car, are today mainly cost and quality-driven. In order to integrate CO2e as decision criterion for supplier selections, site-specific and comparable data on CO2e emissions from the upstream supply chain is necessary, but currently lacking. To estimate CO2e emissions of steel suppliers’ production sites, a model has been developed to estimate manufacturing processes on a site-specific level without the necessity of confidential primary data. The model is applied on 22 integrated steel mills in EU-15. The results, which can be transferred and used for various products and industries, e.g. the construction industry, demonstrate the partially large disparities of manufacturing efficiency regarding CO2e emissions among steel manufacturers due to different levels of process integration and internal process know-how. A range between 1879 and 2990 (kg CO2e/t crude steel) has been revealed. Finally, the estimated data on CO2e performance of suppliers is applied in a case study of supplier selection of a German automobile manufacturer in order to simulate environmental as well as economic effects.
Rapidly decreased HBV RNA predicts responses of pegylated interferons in HBeAg-positive patients: a longitudinal cohort study
Authors: Zhang Min , Li Guangdi , Shang Jia , Pan Chen , Zhang Minxiang , Yin Zhibiao , Xie Qing , Peng Yanzhong , Mao Qing , Xiao Xinqiang , Jiang Yongfang , Luo Kaizhong , Xu Yun , Ding Hai , Fan Wenzhou , Diego Vidaurre , Pourkarim Mahmoud Reza , De Clercq Erik , Wang Guiqiang , Gong Guozhong
Published: February 2020

Background

As an important anti-HBV drug, pegylated interferon α (PegIFNα) offers promising clinical efficacy, but biomarkers that accurately forecast treatment responses are yet to be elucidated. Here, we evaluated whether HBV RNA could act as an early monitor of pegylated interferon responses.

Methods

We analyzed a phase 3, multicenter, randomized cohort of 727 HBeAg-positive non-cirrhotic patients receiving a 48-week treatment of PegIFNα-2a or PegIFNα-2b and a 24-week treatment-free follow-up. Serum levels of HBV RNA, HBV DNA, HBeAg, and HBsAg were measured at weeks 0, 12, 24, 48, and 72.

Results

HBeAg seroconversion and HBsAg loss at week 72 were observed in 217 (29.8%) and 21 (2.9%) patients, respectively. During the 48-week treatment, HBV RNA decreased more rapidly than HBV DNA and HBsAg, but HBV RNA and HBeAg shared similar dynamics with positive correlations. Multivariate regression analyses consistently revealed the significance of HBV RNA at weeks 0, 12, 24, and 48 to monitor HBeAg seroconversion but not HBsAg loss. Although baseline HBV RNA only showed a modest AUC performance, HBV RNA with a significant increase of AUC at week 12 outperformed other HBV biomarkers to forecast HBeAg seroconversion (p value < 0.05). HBV RNA ≤ 1000 copies/mL was an optimized cutoff at week 12 that offered better prediction than other HBV biomarkers. This optimized cutoff plus patient age, HBV genotype B, and HBeAg offered a strong estimation of HBeAg seroconversion (accuracy 95.2%, true negative rate 99.8%).

Conclusion

HBV RNA at week 12 is an effective monitor of HBeAg seroconversion in HBeAg-positive patients treated with pegylated interferons.
Core, intertwined, and ecosystem-specific clusters in platform ecosystems: analyzing similarities in the digital transformation of the automotive, blockchain, financial, insurance and IIoT industry
Authors: Riasanow Tobias , Jäntgen Lea , Hermes Sebastian , Böhm Markus , Krcmar Helmut
Published: February 2020

Digital transformation is continuously changing ecosystems, which also forces established companies to re-evaluate their value proposition. However, only transformations of single ecosystems have been studied. Therefore, this work targets to examine the similarities of digital transformation in five platform ecosystems: automotive, blockchain, financial, insurance, and IIoT. For our analysis, we combine the strengths of conceptual modeling using e3 value with a cluster analysis based on text mining to identify similarities in the respective ecosystems. As a result, we identified 15 clusters. Cluster 01 is the core cluster, containing the roles of organizations from all five ecosystems. Cluster 02–05 are intertwined, as they include roles from at least two ecosystems. Clusters 06–15 are ecosystem-specific that only include roles found in one ecosystem. Scholars and practitioners can use these clusters when analyzing or building a new platform ecosystem, or transforming a traditional ecosystem towards a platform ecosystem.
Lower Tithonian and lower Berriasian brachiopods from the Márévár Limestone Formation, Zengővárkony (Mecsek Mountains Hungary), and remarks on their palaeoenvironment
Authors: Bujtor László , Albrecht Richárd , Maróti Dávid , Miklósy Ákos
Published: February 2020

A new collection provided some brachiopods assigned to Lacunosella hoheneggeri, Pygope diphya and P. janitor from the lower Tithonian (Micracanthoceras ponti Zone) and lower Berriasian (Calpionella Zone), and from the limestone succession at Zengővárkony, Mecsek Mountains, Hungary. This is the first taxonomic description and photographic documentation of these fossils. We provide reliable documentation of pygopid brachiopods from the Mecsek Mountains, known since 1880, but previously not described. For the moment, three pygopid brachiopod species are reliably reported from the Mecsek Mountains: Pygope diphya, P. janitor and Pygites diphyioides. The Lacunosella hoheneggeri described herein is the first record of Berriasian rhynchonellide brachiopods from the Mecsek Mountains. The lower Berriasian brachiopods may belong to a normal palaeoenvironment, with the usual size distribution.
Toxizität der Tabakpflanze (Giftpflanze des Jahres 2009)
Authors: Kloft A.-L. , Zulauf N. , Oremek G. M.
Published: February 2020

Die Gattungen Nicotiana tabacum und Nicotiana rustica der Tabakpflanze sind von großer wirtschaftlicher Bedeutung. Aus ihnen wird Tabak hergestellt, der mit Alkohol zur weltweit am häufigsten konsumierten Genussdroge zählt. Aufgrund seiner Legalität wird die Toxizität trotz steigender Warnung und Aufklärung immer noch unterschätzt. Die Toxizität der Tabakpflanze ist vor allem auf das Alkaloid Nikotin zurückzuführen. Dass es selten zu einer Vergiftung durch die reine Pflanze kommt, liegt daran, dass sie optisch kaum zum Verzehr anregt. Häufiger dagegen ist eine Vergiftung durch z. B. verschluckte Zigarettenstummel, die vor allem für Kinder sehr gefährlich sein kann. Eine weitere Gefahr der Vergiftung entsteht bei der Tabakernte. Nikotin wird auch über die Haut aufgenommen und kann so zu der Green Tobacco Sickness bei Tabakplantagenarbeitern führen. Im Ernstfall existiert kein Antidot. Aktivkohle sollte so schnell wie möglich gegeben werden, um die Resorption zu vermindern. Ansonsten muss das Nikotin mit einer Magenwäsche aus dem Körper gefiltert werden. Präventiv sollten deshalb verstärkt auf die Gefahren des Tabaks aufmerksam gemacht werden.
A Self-supported Graphene/Carbon Nanotube Hollow Fiber for Integrated Energy Conversion and Storage
Authors: Liu Kai , Chen Zilin , Lv Tian , Yao Yao , Li Ning , Li Huili , Chen Tao
Published: February 2020

Wearable fiber-shaped integrated energy conversion and storage devices have attracted increasing attention, but it remains a big challenge to achieve a common fiber electrode for both energy conversion and storage with high performance. Here, we grow aligned carbon nanotubes (CNTs) array on continuous graphene (G) tube, and their seamlessly connected structure provides the obtained G/CNTs composite fiber with a unique self-supported hollow structure. Taking advantage of the hollow structure, other active materials (e.g., polyaniline, PANI) could be easily functionalized on both inner and outer surfaces of the tube, and the obtained G/CNTs/PANI composite hollow fibers achieve a high mass loading (90%) of PANI. The G/CNTs/PANI composite hollow fibers can not only be used for high-performance fiber-shaped supercapacitor with large specific capacitance of 472 mF cm−2, but also can replace platinum wire to build fiber-shaped dye-sensitized solar cell (DSSC) with a high power conversion efficiency of 4.20%. As desired, the integrated device of DSSC and supercapacitor with the G/CNTs/PANI composite hollow fiber used as the common electrode exhibits a total power conversion and storage efficiency as high as 2.1%. Furthermore, the self-supported G/CNTs hollow fiber could be further functionalized with other active materials for building other flexible and wearable electronics.
An Experimental Analysis of the Effectiveness of Multi-Screen Advertising
Authors: Hoeck Lena , Spann Martin
Published: February 2020

Multiscreening refers to consumers’ simultaneous usage of multiple screen-based devices. Prior research has shown that simultaneous multiscreening distracts consumers and hinders cognitive processing. In this paper, we evaluate whether and how simultaneous multiscreening can harm advertising effectiveness. Moreover, we test under which conditions an additional mobile advertising impression can moderate the effect of multiscreening on advertising effectiveness. We test the impact of multiscreening via different screen-based devices in two experiments. We find that multiscreening decreases advertising effectiveness and show that an additional mobile advertising impression of the same brand can attenuate the effect, but only when the additional mobile advertisement does not lead to high levels of distraction from the desktop advertisement.
Parents still matter! Parental warmth predicts adolescent brain function and anxiety and depressive symptoms 2 years later
Authors: Butterfield Rosalind D. , Silk Jennifer S. , Lee Kyung Hwa , Siegle Greg S. , Dahl Ronald E. , Forbes Erika E. , Ryan Neal D. , Hooley Jill M. , Ladouceur Cecile D.
Published: February 2020

Anxiety is the most prevalent psychological disorder among youth, and even following treatment, it confers risk for anxiety relapse and the development of depression. Anxiety disorders are associated with heightened response to negative affective stimuli in the brain networks that underlie emotion processing. One factor that can attenuate the symptoms of anxiety and depression in high-risk youth is parental warmth. The current study investigates whether parental warmth helps to protect against future anxiety and depressive symptoms in adolescents with histories of anxiety and whether neural functioning in the brain regions that are implicated in emotion processing and regulation can account for this link. Following treatment for anxiety disorder (Time 1), 30 adolescents (Mage = 11.58,SD= 1.26) reported on maternal warmth, and 2 years later (Time 2) they participated in a functional neuroimaging task where they listened to prerecorded criticism and neutral statements from a parent. Higher maternal warmth predicted lower neural activation during criticism, compared with the response during neutral statements, in the left amygdala, bilateral insula, subgenual anterior cingulate (sgACC), right ventrolateral prefrontal cortex, and anterior cingulate cortex. Maternal warmth was associated with adolescents’ anxiety and depressive symptoms due to the indirect effects of sgACC activation, suggesting that parenting may attenuate risk for internalizing through its effects on brain function.
A channel-based perspective on conjugate priors
Authors: Jacobs B.
Published: February 2020

A desired closure property in Bayesian probability is that an updated posterior distribution be in the same class of distributions – say Gaussians – as the prior distribution. When the updating takes place via a statistical model, one calls the class of prior distributions the ‘conjugate priors’ of the model. This paper gives (1) an abstract formulation of this notion of conjugate prior, using channels, in a graphical language, (2) a simple abstract proof that such conjugate priors yield Bayesian inversions and (3) an extension to multiple updates. The theory is illustrated with several standard examples.
Urban Renewal Can Mitigate Urban Heat Islands
Authors: Wang Wei , Shu Jiong
Published: February 2020

How can urban renewal effectively contribute to urban climate? Shanghai, one of the world's first metropolises to utilize effective urban heat island (UHI) mitigation strategies, is investigated by analyzing meteorological and land use observations over the past 144 years. The UHI decreased by ~0.58 °C between 2005 and 2016 due to urban renewal characterized by an increase in vegetation cover and the closure of the high‐energy consumption industries in urban areas. Simulation results also indicate that future mitigation strategies should strive to increase vegetation cover, as a 10–20% increase in vegetation cover is anticipated to reduce the UHI by 0.38–0.78 °C, resulting in potential electricity savings of 3.05–5.79 × 108 kWh/year, which correspond to a carbon emissions reduction of 2.47–4.68 × 105 tCO2/year. The results will contribute to improve urban climate associated with large‐scale urbanization and will provide guidance for urban renewal in other metropolises worldwide.
A Machine Learning Approach to Developing Ground Motion Models From Simulated Ground Motions
Authors: Withers Kyle B. , Moschetti Morgan P. , Thompson Eric M.
Published: February 2020

We use a machine learning approach to build a ground motion model (GMM) from a synthetic database of ground motions extracted from the Southern California CyberShake study. An artificial neural network is used to find the optimal weights that best fit the target data (without overfitting), with input parameters chosen to match that of state‐of‐the‐art GMMs. We validate our synthetic‐based GMM with empirically based GMMs derived from the globally based Next Generation Attenuation West2 data set, finding near‐zero median residuals and similar amplitude and trends (with period) of total variability. Additionally, we find that the artificial neural network GMM has similar bias and variability to empirical GMMs from records of the recent
Ridgecrest event, which neither GMM has included in its formulation. As simulations continue to better model broadband ground motions, machine learning provides a way to utilize the vast amount of synthetically generated data and guide future parameterization of GMMs.
Quantifying Event‐Specific Radial Diffusion Coefficients of Radiation Belt Electrons With the PPMLR‐MHD Simulation
Authors: Li Li‐Fang , Tu Weichao , Dai Lei , Tang Bin‐Bin , Wang Chi , Barani Mohammad , Zeng Gang , Wei Chao , Burch J.L.
Published: February 2020

Using the global Lagrangian version of the piecewise parabolic method‐magnetohydrodynamic (PPMLR‐MHD) model, we simulate two consecutive storms in December 2015, a moderate storm on 14–15 December and a strong storm on 19–22 December, and calculate the radial diffusion coefficients (DLL) from the simulated ultralow frequency waves. We find that even though the strong storm leads to more enhanced Bz and Eφ power than the moderate storm, the two storms share in common a lot of features on the azimuthal mode structure and power spectrum of ultralow frequency waves. For both storms, the total Bz and Eφ power is better correlated with the solar wind dynamic pressure in the storm initial phase and more correlated with AE index in the recovery phase. Bz wave power is shown to be mostly distributed in low mode numbers, while Eφ power spreads over a wider range of modes. Furthermore, the Bz and Eφ power spectral densities are found to be higher at higher L regions, with a stronger L dependence in the Bz spectra. The estimated DLL based on MHD fields shows that inside the magnetopause, the contribution from electric fields is larger than or comparable to that from magnetic fields, and our event‐specific MHD‐based DLL can be smaller than some previous empirical DLL estimations by more than an order of magnitude. At last, by validating against in situ observations from Magnetospheric Multiscale spacecraft, our MHD results are found to generally well reproduce the total Bz fields and wave power for both storms, while the Eφ power is underestimated in the MHD simulations.
Maureen E. Raymo Receives 2019 Maurice Ewing Medal
Authors:   AGU
Published: February 2020

Maureen E. Raymo was awarded the 2019 Maurice Ewing Medal at AGU’s Fall Meeting 2019 Honors Ceremony, held on 11 December 2019 in San Francisco, Calif. The medal is for “significant original contributions to the ocean sciences.”
Eugenia Kalnay Receives 2019 Roger Revelle Medal
Authors:   AGU
Published: February 2020

Eugenia Kalnay was awarded the 2019 Roger Revelle Medal at AGU’s Fall Meeting 2019 Honors Ceremony, held on 11 December 2019 in San Francisco, Calif. The medal is for “outstanding contributions in atmospheric sciences, atmosphere-ocean coupling, atmosphere-land coupling, biogeochemical cycles, climate or related aspects of the Earth system.”
Kuljeet Kaur Marhas Receives 2019 Devendra Lal Memorial Medal
Authors:   AGU
Published: February 2020

Kuljeet Kaur Marhas was awarded the 2019 Devendra Lal Memorial Medal at the AGU Fall Meeting Honors Ceremony, held on 11 December 2019 in San Francisco, Calif. The medal is for “outstanding Earth and/or space sciences research by a scientist belonging to and working in a developing country.”
Wildfires, Coal Fires, and Other Things to Get Fired Up About
Authors:   AGU
Published: February 2020

What Earth and space science stories are we recommending this week?
The Shape of Watersheds
Authors: Thomasy Hannah
Published: February 2020

Streams in flatter watersheds have carbon cycles more sensitive to temperature increases.
What Is Left in the Air After a Wildfire Depends on Exactly What Burned
Authors: Sever Megan
Published: February 2020

Forecasting air quality after a wildfire is improving, thanks to more-refined models that measure the biomass going into the blaze and the emissions coming out.
Students Launch Balloon-Borne Payloads into Thunderstorms
Authors: Kornei Katherine
Published: February 2020

The High Energy Lightning Emission Network project hopes to detect elusive bursts of light and particles called terrestrial gamma ray flashes.
Profits for the Planet
Authors: Howley Korena
Published: February 2020

Entrepreneurs are addressing global challenges with science-based—and financially sustainable—solutions.
Where Do Natural Gas Hydrates Come from and Why Should We Care?
Authors: You Kehua , Flemings Peter
Published: February 2020

A new generation of models, laboratory, and field studies is helping scientists answer important questions about this mysterious substance.
Bill Calls for Dramatically Cutting Plastic Pollution
Authors: Showstack Randy
Published: February 2020

With just 8% of plastic waste in the United States currently being recycled, the bill aims to set up an effective plastic recycling program and limit single-use plastic.
Fluid Pressure Changes Grease Cascadia’s Slow Aseismic Earthquakes
Authors: Morton Mary
Published: February 2020

Twenty-five years’ worth of data allows scientists to suss out subtle signals deep in subduction zones.
Basu, Ismail-Zadeh, Leinen, Millar, and Wu Receive 2019 Ambassador Awards
Authors:   AGU
Published: February 2020

Sunanda Basu, Alik Ismail-Zadeh, Margaret Leinen, Connie Millar, and Lixin Wu were awarded the 2019 Ambassador Award at the AGU Fall Meeting Honors Ceremony, held on 11 December 2019 in San Francisco, Calif. The award is for “outstanding contributions to one or more of the following areas: societal impact, service to the Earth and space community, scientific leadership, and promotion of talent/career pool.”
Reply to Comment by Jie Qin and Teng Wu on “A Modified Particle Filter‐Based Data Assimilation Method for a High‐Precision 2‐D Hydrodynamic Model Considering Spatial‐Temporal Variability of Roughness: Simulation of Dam‐Break Flood Inundation”
Authors: Cao Yin , Ye Yuntao , Liang Lili , Zhao Hongli , Jiang Yunzhong , Wang Hao , Yi Zhenyan , Shang Yizi , Yan Dengming
Published: February 2020

Key Points

The MPFDA‐LW could offset the unknown model errors by only adjusting the Manning's roughness coefficient

The observation error in the MPFDA‐LW was determined by sensitivity analysis due to unknown truth observation error

In order to improve the prediction of whole flood process, water stages observed in a regional scale should be assimilated
High-frequency neuronavigated rTMS effect on clinical symptoms and cognitive dysfunction: a pilot double-blind, randomized controlled study in Veterans with schizophrenia
Authors: Guan Heng Yong , Zhao Jian Min , Wang Ke Qiang , Su Xiu Ru , Pan Yan Fen , Guo Jin Ming , Jiang Long , Wang Yu Hong , Liu Hong Yu , Sun Shi Guang , Wu Hao Ran , Ren Yan Ping , Geng Han Song , Liu Xiao Wen , Yu Hui Jing , Wei Bao Chun , Li Xi Po , Wu Hanjing Emily , Tan Shu Ping , Xiu Mei Hong , Zhang Xiang Yang
Published: February 2020

Cognitive impairment is a central aspect of schizophrenia (SCZ) that occurs at the onset of the disease and is related to poor social function and outcome in patients with SCZ. Recent literatures have revealed repetitive transcranial magnetic stimulation (rTMS) to be one of the efficient medical interventions for cognitive impairments. However, no study has been conducted to investigate the treatment effectiveness of 20 Hz rTMS with neuronavigation system administered to the left dorsolateral prefrontal cortex (DLPFC) in patients with schizophrenia. In this randomized, double-blind and sham-controlled study, 56 patients were enrolled in 20 Hz rTMS (n = 28) or sham stimulation (n = 28) over left DLPFC for 8 weeks. The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) was performed to measure the cognitive function at baseline and after 8 weeks of rTMS treatment. The positive and negative syndrome scales (PANSS) was performed to assess the clinical symptoms at baseline, after 2-week treatment, 4-week treatment, 6-week treatment, and 8-week treatment. Totally, 15 subjects (seven in active group and eight in sham group) dropped out during the trial and the main findings were from completed 41 patients. At 2 weeks, 4 weeks, and 6 weeks, there were no significant differences in PANSS total score and subscores between the sham and treatment groups. At 8 weeks, the 20 Hz rTMS significantly increased the immediate memory score compared with the sham. Furthermore, the improvement in the immediate memory score was correlated with the decrease in the excitement factor score of the patients with SCZ. Our results suggest that 20 Hz rTMS appears to be an effective treatment for improving the cognitive performance and reducing the clinical symptoms of patients with SCZ.
The new WHO classification for essential thrombocythemia calls for revision of available evidences
Authors: Barbui Tiziano , Thiele Jürgen , Ferrari Alberto , Vannucchi Alessandro M. , Tefferi Ayalew
Published: February 2020

In the 2016 revised classification of myeloproliferative neoplasms pre-fibrotic primary myelofibrosis (pre-PMF) was recognized as a separate entity, distinct from essential thrombocythemia (ET). Owing that the majority of cases falling in the pre-PMF category were previously diagnosed as ET, one may question about the need to re-evaluate the results of epidemiologic, clinical, and molecular studies, and the results of clinical trials in the two entities. Based on a critical review of recently published studies, pre-PMF usually presents with a distinct clinical and hematological presentation and higher frequency of constitutional symptoms. JAK2V617F and CALR mutations in pre-PMF patients are superimposable to ET, whereas non-driver high-risk mutations are enriched in pre-PMF compared with ET. Thrombosis is not significantly different, whereas bleeding is more frequent in pre-PMF. Median survival is significantly shorter in pre-PMF and 10-year cumulative rates progression to overt myelofibrosis is 0–1% vs. 10–12%, and leukemic transformation is 1–2% vs. 2–6%, in ET and pre-fibrotic-PMF, respectively. Most patients fall in the lower prognostic IPSS group in which observation alone can be recommended. Patients at intermediate risk may require a symptom-driven treatment for anemia, splenomegaly or constitutional symptoms while cytoreductive drugs are indicated in the high-risk category.
Blood mass spectrometry detects residual disease better than standard techniques in light-chain amyloidosis
Authors: Dispenzieri Angela , Arendt Bonnie , Dasari Surendra , Kohlhagen Mindy , Kourelis Taxiarchis , Kumar Shaji K. , Leung Nelson , Muchtar Eli , Buadi Francis K. , Warsame Rahma , Kyle Robert A. , Lacy Martha Q. , Dingli David , Kapoor Prashant , Gonsalves Wilson I. , Go Ronald S. , Hayman Suzanne R. , Hwa Yi Lisa , Fonder Amy , Hobbs Miriam , Jevremovic Dragan , Lust John A. , Zeldenrust Steven , Russell Steve J. , Rajkumar S. Vincent , Gertz Morie A. , Murray David
Published: February 2020

In patients with immunoglobulin light-chain (AL) amyloidosis, depth of hematologic response correlates with both organ response and overall survival. Our group has demonstrated that screening with a matrix-assisted laser desorption/ionization-time-of-flight (TOF) mass spectrometry (MS) is a quick, sensitive, and accurate means to diagnose and monitor the serum of patients with plasma cell disorders. Microflow liquid chromatography coupled with electrospray ionization and quadrupole TOF MS adds further sensitivity. We identified 33 patients with AL amyloidosis who achieved amyloid complete hematologic response, who also had negative bone marrow by six-color flow cytometry, and who had paired serum samples to test by MS. These samples were subjected to blood MS. Four patients (12%) were found to have residual disease by these techniques. The presence of residual disease by MS was associated with a poorer time to progression (at 50 months 75% versus 13%, p = 0.003). MS of the blood out-performed serum and urine immunofixation, the serum immunoglobulin free light chain, and six-color flow cytometry of the bone marrow in detecting residual disease. Additional studies that include urine MS and next-generation techniques to detect clonal plasma cells in the bone marrow will further elucidate the full potential of this technique.
Connecting energetics to dynamics in particle growth by oriented attachment using real-time observations
Authors: Liu Lili , Nakouzi Elias , Sushko Maria L. , Schenter Gregory K. , Mundy Christopher J. , Chun Jaehun , De Yoreo James J.
Published: February 2020

The interplay between crystal and solvent structure, interparticle forces and ensemble particle response dynamics governs the process of crystallization by oriented attachment (OA), yet a quantitative understanding is lacking. Using ZnO as a model system, we combine in situ TEM observations of single particle and ensemble assembly dynamics with simulations of interparticle forces and responses to relate experimentally derived interparticle potentials to the underlying interactions. We show that OA is driven by forces and torques due to a combination of electrostatic ion-solvent correlations and dipolar interactions that act at separations well beyond 5 nm. Importantly, coalignment is achieved before particles reach separations at which strong attractions drive the final jump to contact. The observed barrier to attachment is negligible, while dissipative factors in the quasi-2D confinement of the TEM fluid cell lead to abnormal diffusivities with timescales for rotation much less than for translation, thus enabling OA to dominate.
A silicate dynamo in the early Earth
Authors: Stixrude Lars , Scipioni Roberto , Desjarlais Michael P.
Published: February 2020

The Earth’s magnetic field has operated for at least 3.4 billion years, yet how the ancient field was produced is still unknown. The core in the early Earth was surrounded by a molten silicate layer, a basal magma ocean that may have survived for more than one billion years. Here we use density functional theory-based molecular dynamics simulations to predict the electrical conductivity of silicate liquid at the conditions of the basal magma ocean: 100–140 GPa, and 4000–6000 K. We find that the electrical conductivity exceeds 10,000 S/m, more than 100 times that measured in silicate liquids at low pressure and temperature. The magnetic Reynolds number computed from our results exceeds the threshold for dynamo activity and the magnetic field strength is similar to that observed in the Archean paleomagnetic record. We therefore conclude that the Archean field was produced by the basal magma ocean.
Silica accelerates the selective hydrogenation of CO2 to methanol on cobalt catalysts
Authors: Wang Lingxiang , Guan Erjia , Wang Yeqing , Wang Liang , Gong Zhongmiao , Cui Yi , Meng Xiangju , Gates Bruce C. , Xiao Feng-Shou
Published: February 2020

The reaction pathways on supported catalysts can be tuned by optimizing the catalyst structures, which helps the development of efficient catalysts. Such design is particularly desired for CO2 hydrogenation, which is characterized by complex pathways and multiple products. Here, we report an investigation of supported cobalt, which is known for its hydrocarbon production and ability to turn into a selective catalyst for methanol synthesis in CO2 hydrogenation which exhibits good activity and stability. The crucial technique is to use the silica, acting as a support and ligand, to modify the cobalt species via Co‒O‒SiOn linkages, which favor the reactivity of spectroscopically identified *CH3O intermediates, that more readily undergo hydrogenation to methanol than the C‒O dissociation associated with hydrocarbon formation. Cobalt catalysts in this class offer appealing opportunities for optimizing selectivity in CO2 hydrogenation and producing high-grade methanol. By identifying this function of silica, we provide support for rationally controlling these reaction pathways.
Optogenetic engineering to probe the molecular choreography of STIM1-mediated cell signaling
Authors: Ma Guolin , He Lian , Liu Shuzhong , Xie Jiansheng , Huang Zixian , Jing Ji , Lee Yi-Tsang , Wang Rui , Luo Hesheng , Han Weidong , Huang Yun , Zhou Yubin
Published: February 2020

Genetically encoded photoswitches have enabled spatial and temporal control of cellular events to achieve tailored functions in living cells, but their applications to probe the structure-function relations of signaling proteins are still underexplored. We illustrate herein the incorporation of various blue light-responsive photoreceptors into modular domains of the stromal interaction molecule 1 (STIM1) to manipulate protein activity and faithfully recapitulate STIM1-mediated signaling events. Capitalizing on these optogenetic tools, we identify the molecular determinants required to mediate protein oligomerization, intramolecular conformational switch, and protein-target interactions. In parallel, we have applied these synthetic devices to enable light-inducible gating of calcium channels, conformational switch, dynamic protein-microtubule interactions and assembly of membrane contact sites in a reversible manner. Our optogenetic engineering approach can be broadly applied to aid the mechanistic dissection of cell signaling, as well as non-invasive interrogation of physiological processes with high precision.
Measuring single cell divisions in human tissues from multi-region sequencing data
Authors: Werner Benjamin , Case Jack , Williams Marc J. , Chkhaidze Ketevan , Temko Daniel , Fernández-Mateos Javier , Cresswell George D. , Nichol Daniel , Cross William , Spiteri Inmaculada , Huang Weini , Tomlinson Ian P. M. , Barnes Chris P. , Graham Trevor A. , Sottoriva Andrea
Published: February 2020

Both normal tissue development and cancer growth are driven by a branching process of cell division and mutation accumulation that leads to intra-tissue genetic heterogeneity. However, quantifying somatic evolution in humans remains challenging. Here, we show that multi-sample genomic data from a single time point of normal and cancer tissues contains information on single-cell divisions. We present a new theoretical framework that, applied to whole-genome sequencing data of healthy tissue and cancer, allows inferring the mutation rate and the cell survival/death rate per division. On average, we found that cells accumulate 1.14 mutations per cell division in healthy haematopoiesis and 1.37 mutations per division in brain development. In both tissues, cell survival was maximal during early development. Analysis of 131 biopsies from 16 tumours showed 4 to 100 times increased mutation rates compared to healthy development and substantial inter-patient variation of cell survival/death rates.
Publisher Correction: An expression atlas of variant ionotropic glutamate receptors identifies a molecular basis of carbonation sensing
Authors: Sánchez-Alcañiz Juan Antonio , Silbering Ana Florencia , Croset Vincent , Zappia Giovanna , Sivasubramaniam Anantha Krishna , Abuin Liliane , Sahai Saumya Yashmohini , Münch Daniel , Steck Kathrin , Auer Thomas O. , Cruchet Steeve , Neagu-Maier G. Larisa , Sprecher Simon G. , Ribeiro Carlos , Yapici Nilay , Benton Richard
Published: February 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Entropy and interfacial energy driven self-healable polymers
Authors: Hornat Chris C. , Urban Marek W.
Published: February 2020

Although significant advances have been achieved in dynamic reversible covalent and non-covalent bonding chemistries for self-healing polymers, an ultimate goal is to create high strength and stiffness commodity materials capable of repair without intervention under ambient conditions. Here we report the development of mechanically robust thermoplastic polyurethane fibers and films capable of autonomous self-healing under ambient conditions. Two mechanisms of self-healing are identified: viscoelastic shape memory (VESM) driven by conformational entropic energy stored during mechanical damage, and surface energy/tension that drives the reduction of newly generated surface areas created upon damage by shallowing and widening wounds until healed. The type of self-healing mechanism is molecular weight dependent. To the best of our knowledge these materials represent the strongest (Sf = 21 mN/tex, or σf ≈ 22 MPa) and stiffest (J = 300 mN/tex, or E ≈ 320 MPa) self-healing polymers able to repair under typical ambient conditions without intervention. Since two autonomous self-healing mechanisms result from viscoelastic behavior not specific to a particular polymer chemistry, they may serve as general approaches to design of other self-repairing commodity polymers.
Author Correction: De novo identification of essential protein domains from CRISPR-Cas9 tiling-sgRNA knockout screens
Authors: He Wei , Zhang Liang , Villarreal Oscar D. , Fu Rongjie , Bedford Ella , Dou Jingzhuang , Patel Anish Y. , Bedford Mark T. , Shi Xiaobing , Chen Taiping , Bartholomew Blaine , Xu Han
Published: February 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
γ-Aminobutyric acid confers cadmium tolerance in maize plants by concerted regulation of polyamine metabolism and antioxidant defense systems
Authors: Seifikalhor Maryam , Aliniaeifard Sasan , Bernard Françoise , Seif Mehdi , Latifi Mojgan , Hassani Batool , Didaran Fardad , Bosacchi Massimo , Rezadoost Hassan , Li Tao
Published: February 2020

Gamma-Aminobutyric acid (GABA) accumulates in plants following exposure to heavy metals. To investigate the role of GABA in cadmium (Cd) tolerance and elucidate the underlying mechanisms, GABA (0, 25 and 50 µM) was applied to Cd-treated maize plants. Vegetative growth parameters were improved in both Cd-treated and control plants due to GABA application. Cd uptake and translocation were considerably inhibited by GABA. Antioxidant enzyme activity was enhanced in plants subjected to Cd. Concurrently GABA caused further increases in catalase and superoxide dismutase activities, which led to a significant reduction in hydrogen peroxide, superoxide anion and malondealdehyde contents under stress conditions. Polyamine biosynthesis-responsive genes, namely ornithine decarboxylase and spermidine synthase, were induced by GABA in plants grown under Cd shock. GABA suppressed polyamine oxidase, a gene related to polyamine catabolism, when plants were exposed to Cd. Consequently, different forms of polyamines were elevated in Cd-exposed plants following GABA application. The maximum quantum efficiency of photosystem II (Fv/Fm) was decreased by Cd-exposed plants, but was completely restored by GABA to the same value in the control. These results suggest a multifaceted contribution of GABA, through regulation of Cd uptake, production of reactive oxygen species and polyamine metabolism, in response to Cd stress.
Machine learning identifies a strong association between warming and reduced primary productivity in an oligotrophic ocean gyre
Authors: D’Alelio Domenico , Rampone Salvatore , Cusano Luigi Maria , Morfino Valerio , Russo Luca , Sanseverino Nadia , Cloern James E. , Lomas Michael W.
Published: February 2020

Phytoplankton play key roles in the oceans by regulating global biogeochemical cycles and production in marine food webs. Global warming is thought to affect phytoplankton production both directly, by impacting their photosynthetic metabolism, and indirectly by modifying the physical environment in which they grow. In this respect, the Bermuda Atlantic Time-series Study (BATS) in the Sargasso Sea (North Atlantic gyre) provides a unique opportunity to explore effects of warming on phytoplankton production across the vast oligotrophic ocean regions because it is one of the few multidecadal records of measured net primary productivity (NPP). We analysed the time series of phytoplankton primary productivity at BATS site using machine learning techniques (ML) to show that increased water temperature over a 27-year period (1990–2016), and the consequent weakening of vertical mixing in the upper ocean, induced a negative feedback on phytoplankton productivity by reducing the availability of essential resources, nitrogen and light. The unbalanced availability of these resources with warming, coupled with ecological changes at the community level, is expected to intensify the oligotrophic state of open-ocean regions that are far from land-based nutrient sources.
Holothurians have a reduced GPCR and odorant receptor-like repertoire compared to other echinoderms
Authors: Marquet Nathalie , Cardoso João C. R. , Louro Bruno , Fernandes Stefan A. , Silva Sandra C. , Canário Adelino V. M.
Published: February 2020

Sea cucumbers lack vision and rely on chemical sensing to reproduce and survive. However, how they recognize and respond to environmental cues remains unknown. Possible candidates are the odorant receptors (ORs), a diverse family of G protein-coupled receptors (GPCRs) involved in olfaction. The present study aimed at characterizing the chemosensory GPCRs in sea cucumbers. At least 246 distinct GPCRs, of whichca. 20% putative ORs, were found in a transcriptome assembly of putative chemosensory (tentacles, oral cavity, calcareous ring, and papillae/tegument) and reproductive (ovary and testis) tissues fromHolothuria arguinensis(57 ORs) and in theApostichopus japonicusgenome (79 ORs). The sea cucumber ORs clustered with those of sea urchin and starfish into four main clades of gene expansions sharing a common ancestor and evolving under purifying selection. However, the sea cucumber ORs repertoire was the smallest among the echinoderms and the olfactory receptor signature motif LxxPxYxxxxxLxxxDxxxxxxxxP was better conserved in cluster OR-l1 which also had more members. ORs were expressed in tentacles, oral cavity, calcareous ring, and papillae/tegument, supporting their potential role in chemosensing. This study is the first comprehensive survey of chemosensory GPCRs in sea cucumbers, and provides the molecular basis to understand how they communicate.
Radiation dose reduction for CT-guided intrathecal nusinersen administration in adult patients with spinal muscular atrophy
Authors: Cordts Isabell , Deschauer Marcus , Lingor Paul , Burian Egon , Baum Thomas , Zimmer Claus , Maegerlein Christian , Sollmann Nico
Published: February 2020

Intrathecal administration of nusinersen in adult spinal muscular atrophy (SMA) patients with scoliosis and spondylodesis requires image guidance, which is preferably achieved with multi-detector computed tomography (MDCT). As long-term treatment is necessary and patients are young, radiation doses should be reduced to a minimum whilst a sufficient image quality for precise interventional performance should be kept. We compared 44 MDCT standard-dose scans (133.0–200.0 mA) with a hybrid iterative reconstruction (iDose4) to 20 low-dose scans (20.0–67.0 mA) with iterative model reconstruction (IMR), which were performed for procedure planning of intrathecal nusinersen administration in 13 adult patients with SMA and complex spinal conditions. Qualitative image evaluation, including confidence for intervention planning, was performed by two neuroradiologists for standard- and low-dose scans. All 64 MDCT-guided intrathecal administrations of nusinersen were successful. The dose length product (DLP) was significantly lower when using low-dose scanning with IMR (median DLP of standard-dose scans: 92.0 mGy•cm vs. low-dose scans: 34.5 mGy•cm; p < 0.0001). Image quality was significantly reduced for low-dose compared to standard-dose scanning. However, bone/soft tissue contrast and confidence for intervention planning were not significantly impaired in low-dose MDCT according to both readers, showing good inter-reader agreement. Thus, we hereby demonstrate a low-dose MDCT protocol combined with advanced image reconstruction for scanning during procedure planning as a viable option for image guidance in intrathecal nusinersen treatment of adult SMA patients with complex spinal conditions.