bluuebunny/crossref_metadata_2025 huggingface dataset:
The efficacy of additional surgical resection after endoscopic resection in pT1b esophageal squamous cell carcinoma: A multi-institutional retrospective study in China
Authors: Xue Xuemin , Sun Qi , Jiang Dongxian , Wang Xinran , Liu Yong , Guo Changyuan , Liu Linxiu , Cheng Na , Wang Guiqi , Liu Yueping , Hou Yingyong , Fan Xiangshan , Xue Liyan
Published: August 2022

Background

pT1b esophageal squamous cell carcinoma (ESCC) patients treated by endoscopic resection (ER) required additional treatment with surgical resection (SR) or chemoradiotherapy (CRT) according to 2020 Japan Gastroenterological Endoscopy Society (JGES) guideline. Given the evidences for this recommendation were largely based on small-size studies, our study collected 166 cases of ER-treated pT1b patients in order to investigate the efficacy of additional SR as compared to ER-alone treatment.

Methods

A multi-institutional retrospective study in China was conducted. The pT1b ESCC treated by ER + SR (n = 42) and ER-alone (n = 124) from 2007 to 2018 were recruited. Meanwhile, patients with positive lymphovascular invasion (LVI(+)) and/or with positive vertical margin (VM(+)) were put into high-risk group, and those with both VM(−) and LVI(−) were selected into low-risk group. The clinicopathological parameters, lymph node metastasis (LNM), and survival between ER + SR and ER-alone groups were analyzed.

Results

In high-risk group, concurrent LNM revealed in surgically resected specimens accounted for 52.6% cases in ER + SR group. After surgical removal, the incidence of post-resection LNM dropped down to 5.6%. However, in low-risk group, patients with ER + SR treatment did not exhibit any concurrent LNM in surgically resected specimens, and the incidence of their overall LNM was similar to that in ER-alone group (0% vs. 2.8%, p = 1.000). More importantly, these cases demonstrated significantly shorter overall survival (OS) than that in ER-alone group (81.8% and 100.0%, respectively, at 3 years; log-Rank: P = 0.010).

Conclusions

For ER-treated pT1b patients in high-risk group, additional SR is strongly recommended. However, for those in low-risk group, additional SR does not generate much benefit for clearance of LNM, but brings harm to shorten their OS. Therefore, additional SR is not recommended for ER-treated pT1b patient in low-risk group.
Genetic diversity and molecular evolution of sugarcane mosaic virus, comparing whole genome and coat protein sequence phylogenies
Authors: Muhammad Khalid , Herath Venura , Ahmed Khadija , Tahir Muhammad , Verchot Jeanmarie
Published: August 2022

Sugarcane mosaic virus (SCMV) is a widely distributed potyvirus that causes mosaic disease in sugarcane, maize, sorghum, canna, and other monocot species worldwide. This study used 139 SCMV full-length genome sequences to analyze the phylogenetic relatedness of geographically distinct isolates. The phylogenetic analysis revealed four major groups of SCMV isolates that relate to their primary host. The geographic locations for some isolates appear to be mismatched within the tree, suggesting either that convergent molecular evolution has occurred or that the tree reconstruction produces statistically significant incongruences that create uncertainty in the true evolutionary relationships of these virus isolates. Recombination analysis showed hot spots across most of the genome except in the coat protein (CP) coding region. We examined 161 SCMV CP sequences from the GenBank database, including sequences from samples collected in Pakistan, a region that has not been included in prior phylogenetic studies. These data suggest that the SCMV isolates from sugarcane (Saccharum officinarum) predate isolates from all other hosts, regardless of their geographic origins.
Temporal interpolation of groundwater level hydrographs for regional drought analysis using mixed models
Authors: Marchant B. P. , Cuba D. , Brauns B. , Bloomfield J. P.
Published: August 2022

Large-scale studies of the spatial and temporal variation of groundwater drought status require complete inventories of groundwater levels on regular time steps from many sites so that a standardised drought index can be calculated for each site. However, groundwater levels are often measured sporadically, and inventories include missing or erroneous data. A flexible and efficient modelling framework is developed to fill gaps and regularise data in such inventories. It uses linear mixed models to account for seasonal variation, long-term trends and responses to precipitation and temperature over different temporal scales. The only data required to estimate the models are the groundwater level measurements and freely available gridded weather products. The contribution of each of the four types of trends at a site can be determined and thus the causes of temporal variation of groundwater levels can be interpreted. Validation reveals that the models explain a substantial proportion of groundwater level variation and that the uncertainty of the predictions is accurately quantified. The computation for each site takes less than 130 s and requires little supervision. Hence, the approach is suitable to be upscaled to represent the variation of groundwater levels in large datasets consisting of thousands of boreholes.
Distributional properties of continuous time processes: from CIR to bates
Authors: Okhrin Ostap , Rockinger Michael , Schmid Manuel
Published: August 2022

In this paper, we compute closed-form expressions of moments and comoments for the CIR process which allows us to provide a new construction of the transition probability density based on a moment argument that differs from the historic approach. For Bates’ model with stochastic volatility and jumps, we show that finite difference approximations of higher moments such as the skewness and the kurtosis are unstable and, as a remedy, provide exact analytic formulas for log-returns. Our approach does not assume a constant mean for log-price differentials but correctly incorporates volatility resulting from Ito’s lemma. We also provide R, MATLAB, and Mathematica modules with exact implementations of the theoretical conditional and unconditional moments. These modules should prove useful for empirical research.
Two-sided Sequent Calculi for FDE-like Four-valued Logics
Authors: Kooi Barteld , Tamminga Allard
Published: August 2022

We present a method that generates two-sided sequent calculi for four-valued logics like first degree entailment (FDE). (We say that a logic is FDE-like if it has finitely many operators of finite arity, including negation, and if all of its operators are truth-functional over the four truth-values ‘none’, ‘false’, ‘true’, and ‘both’, where ‘true’ and ‘both’ are designated.) First, we show that for every n-ary operator ⋆ every truth table entry f⋆(x1,…,xn) = y can be characterized in terms of a pair of sequent rules. Secondly, we use these sequent rules to build sequent calculi and prove their completeness. With the help of two simplification procedures we then show that the 2 ⋅ 4n sequent rules that characterize an n-ary operator can be systematically reduced to at most four sequent rules. Thirdly, we use our method to investigate the proof-theoretical consequences of including intuitive truth-functional implications in FDE-like logics.
Ageing population and society: a scientometric analysis
Authors: Mahmood Muhammad N. , Dhakal Subas P.
Published: August 2022

The ageing population and society (APS) nexus is one of the key grand challenges of this millennium. And yet, the systematic analysis of scholarly literature on the APS nexus has remained under the radar. This study responds to this gap and employs a quantitative approach through a scientometric analysis of literature on the APS nexus to inform policy discussions and guide future research directions. This study adopts quantitative scientometric methods to examine the APS literature (n = 566) between 2011 and 2020 found in the Scopus database. The analysis reveals key research topics and recognizes the most important articles, authors, publication outlets, institutions, and countries in the field. The findings indicate that while issues such as ageing population, gender, quality of life, and socio-economic aspects of ageing have received significant interest, social exclusion of older adults, age diversity, social policy, and the eldercare workforce have received less attention. As challenges associated with the APS nexus will continue to gain currency in the future, this paper discusses the implications of the findings on (a) future research direction and (b) north-south research collaboration. The analysis shown in this paper should be of interest to scholars and policymakers interested in addressing the challenges associated with the APS nexus.
Leveraging Leadership in Child Welfare Systems: Large-scale Trauma- and Resilience-informed Training Initiative
Authors: Rodriguez Adriana , Fei Zhe , Barrera Wendy A. , Tsao Eugenia H. , Waterman Jill , Franke Todd M. , Mogil Catherine E. , Bonilla Blanca , Cugley Gita Murthy , Gillams Teri , Langley Audra
Published: August 2022

Strengthening the infrastructure of public health systems around trauma-informed principles is crucial to addressing the needs of traumatized children in the child welfare system. In fact, many local and state initiatives have focused on large-scale evaluation studies to determine the value of training direct service staff on trauma foundations. Less yet is known about the benefits of training leaders on trauma foundations, which is crucial given their unique influence on implementation decisions. The current study evaluates a trauma training delivered to leadership-level stakeholders through a large-scale training initiative for the Los Angeles County Department of Children and Family Services. Findings indicated that leaders improved in trauma knowledge from baseline to post-training and reported changes in their professional wellbeing and leadership approach after the reflective training component. The leadership trauma program may have positive downstream implications for direct service staff, organizational culture, and child and family outcomes.
An approach for the automatic verification of blockchain protocols: the Tweetchain case study
Authors: Raimondo Mariapia , Bernardi Simona , Marrone Stefano , Merseguer José
Published: August 2022

This paper proposes a model-driven approach for the security modelling and analysis of blockchain based protocols. The modelling is built upon the definition of a UML profile, which is able to capture transaction-oriented information. The analysis is based on existing formal analysis tools. In particular, the paper considers the Tweetchain protocol, a recent proposal that leverages online social networks, i.e., Twitter, for extending blockchain to domains with small-value transactions, such as IoT. A specialized textual notation is added to the UML profile to capture features of this protocol. Furthermore, a model transformation is defined to generate a Tamarin model, from the UML models, via an intermediate well-known notation, i.e., the Alice &Bob notation. Finally, Tamarin Prover is used to verify the model of the protocol against some security properties. This work extends a previous one, where the Tamarin formal models were generated by hand. A comparison on the analysis results, both under the functional and non-functional aspects, is reported here too.
Dynamic Capabilities, Internationalization and Growth of Small- and Medium-Sized Enterprises: The Roles of Research and Development Intensity and Collaborative Intensity
Authors: Fredrich Viktor , Gudergan Siegfried , Bouncken Ricarda B.
Published: August 2022

Small- and medium-sized enterprises (SMEs) can benefit from internationalization. However, there is little evidence of the extent of the benefit and its dependence on both research and development (R&D) intensity and collaborative intensity. Drawing on data of 262 SMEs, this study illuminates why some SMEs benefit more from internationalization than others, thereby illustrating an advanced application of partial least squares structural equation modeling by demonstrating conditional mediation analysis with two interdependent exogenous moderators (i.e., testing a second-stage three-way conditional mediation). Our findings substantiate that an SME’s dynamic capabilities affect its degree of internationalization and indirectly its growth, and suggest a positive marginal growth impact of internationalization provided that an SME’s R&D and collaborative intensities are proportional; when they are disproportional (i.e., one is “greater” than the other), SMEs do not experience positive marginal growth.
Surface Defects on Semicoherent and Incoherent NaCl-Type Carbides Dispersed in Hot-Rolled Ferritic Steel
Authors: Kosaka Noriaki , Čížek Jakub
Published: August 2022

The interface structure of semicoherent titanium carbide (TiC) nanoparticles and incoherent micron-sized TiC precipitates in Fe–C–Ti alloy hot-rolled steel sheets was studied by transmission electron microscopy (TEM) and positron annihilation spectrometry (PAS). The TiC nanoparticles were formed by interphase precipitation during the γ-to-α transformation, and the coarse micron-sized TiC precipitates remained in the matrix as undissolved carbides in the slab reheating process before hot rolling. The semicoherent TiC nanoparticles have coherent planes with the Baker–Nutting orientation relationship and incoherent surface almost parallel to {001}
α
planes. The present investigation revealed that positrons are not annihilated inside TiC particles but rather are trapped at open volume misfit defects located at the incoherent interface between TiC particles and the matrix. The positron lifetime related to misfit defects associated with the semicoherent TiC nanoparticles and incoherent micron-sized TiC precipitates was around 240 ps and 500 ps, respectively. Considering the results of TEM observations and the theoretical positron lifetime, it can be concluded that the positron annihilation site related to TiC nanoparticles is located at the incoherent interface and consists of some vacancies.
The diagnosis of aspiration pneumonia in older persons: a systematic review
Authors: Yoshimatsu Yuki , Melgaard Dorte , Westergren Albert , Skrubbeltrang Conni , Smithard David G.
Published: August 2022

Purpose

Community-acquired pneumonia (CAP) is highly common across the world. It is reported that over 90% of CAP in older adults may be due to aspiration. However, the diagnostic criteria for aspiration pneumonia (AP) have not been widely agreed. Is there a consensus on how to diagnose AP? What are the clinical features of patients being diagnosed with AP? We conducted a systematic review to answer these questions.

Methods

We performed a literature search in MEDLINE®, EMBASE, CINHAL, and Cochrane to review the steps taken toward diagnosing AP. Search terms for “aspiration pneumonia” and “aged” were used. Inclusion criteria were: original research, community-acquired AP, age ≥ 75 years old, acute hospital admission.

Results

A total of 10,716 reports were found. Following the removal of duplicates, 7601 were screened, 95 underwent full-text review, and 9 reports were included in the final analysis. Pneumonia was diagnosed using a combination of symptoms, inflammatory markers, and chest imaging findings in most studies. AP was defined as pneumonia with some relation to aspiration or dysphagia. Aspiration was inferred if there was witnessed or prior presumed aspiration, episodes of coughing on food or liquids, relevant underlying conditions, abnormalities on videofluoroscopy or water swallow test, and gravity-dependent distribution of shadows on chest imaging. Patients with AP were older, more frailer, and had more comorbidities than in non-AP.

Conclusion

There is a broad consensus on the clinical criteria to diagnose AP. It is a presumptive diagnosis with regards to patients’ general frailty rather than in relation to swallowing function itself.
Learning with density matrices and random features
Authors: González Fabio A. , Gallego Alejandro , Toledo-Cortés Santiago , Vargas-Calderón Vladimir
Published: August 2022

A density matrix describes the statistical state of a quantum system. It is a powerful formalism to represent both the quantum and classical uncertainty of quantum systems and to express different statistical operations such as measurement, system combination and expectations as linear algebra operations. This paper explores how density matrices can be used as a building block for machine learning models exploiting their ability to straightforwardly combine linear algebra and probability. One of the main results of the paper is to show that density matrices coupled with random Fourier features could approximate arbitrary probability distributions over $$\mathbb {R}^{n}$$

R

n

. Based on this finding the paper builds different models for density estimation, classification and regression. These models are differentiable, so it is possible to integrate them with other differentiable components, such as deep learning architectures and to learn their parameters using gradient-based optimization. In addition, the paper presents optimization-less training strategies based on estimation and model averaging. The models are evaluated in benchmark tasks and the results are reported and discussed.
Wood-derived biochar as thick electrodes for high-rate performance supercapacitors
Authors: Yan Bing , Zheng Jiaojiao , Feng Li , Du Cheng , Jian Shaoju , Yang Weisen , Wu Yimin A. , Jiang Shaohua , He Shuijian , Chen Wei
Published: August 2022

Developing effective electrodes with commercial-level active mass-loading (> 10 mg cm−2) is vital for the practical application of supercapacitors. However, high active mass-loading usually requires thick active mass layer, which severely hinders the ion/electron transport and results in poor capacitive performance. Herein, a self-standing biochar electrode with active mass-loading of ca. 40 mg cm−2 and thickness of 800 µm has been developed from basswood. The basswood was treated with formamide to incorporate N/O in the carbon structure, followed by mild KOH activation to ameliorate the pore size and introduce more O species in the carbon matrix. The as-prepared carbon monoliths possess well conductive carbon skeleton, abundant N/O dopant and 3D porous structure, which are favorable for the ion/electron transport and promoting capacitance performance. The self-standing carbon electrode not only exhibits the maximum areal/mass/volumetric specific capacitance of 5037.5 mF cm−2/172.5 F g−1/63.0 F cm−3 at 2 mA cm−2 (0.05 A g−1), but also displays excellent rate performance with 76% capacitance retention at 500 mA cm−2 (12.5 A g−1) in a symmetric supercapacitor, surpassing the state-of-art biomass-based thick carbon electrode. The assembled model can power typical electron devices including a fan, a digital watch and a logo made up of 34 light-emitting diodes for a proper period, revealing its practical application potential. This study not only puts forward a commercial-level high active mass-loading electrode from biomass for supercapacitor, but also bridges the gap between the experimental research and practical application.

Graphical abstract
Coherentism
Authors: Olsson Erik J.
Published: August 2022

Perhaps the most fundamental question of epistemology asks on what grounds our knowledge of the world ultimately rests. The traditional Cartesian answer is that it rests on indubitable facts arrived at through rational insight or introspection. Coherentists reject this answer, claiming instead that knowledge arises from relations of coherence or mutual support: if our beliefs cohere, we can be sure that they are mostly true. The first part of this Element introduces the reader to the main ideas and problems of coherentism. The next part describes the 'probabilistic turn', leading up to recent demonstrations that coherence fails to be conducive to truth. The final part reassesses the current debate about the proper definition of coherence from the standpoint of Rudolf Carnap's methodology of explication. The upshot is a tentative and qualified defence of one of the early coherence measures.
Global Histories of Modern Europe
Authors: Evans Richard J.
Published: August 2022

The historical profession emerged in Europe in the nineteenth century in tandem with the rise of the nation-state. Historians of the modern period in particular focused above all on the political history of nation-states and the diplomatic history of relations between them. Global aspects of European history were covered mainly in terms of Europe’s impact on other parts of the world, as in Hobsbawm’s “dual revolution” (the worldwide repercussions of the French Revolution and the Industrial Revolution), or the history of Europe’s colonial possessions overseas. And yet there were demonstrable global influences on many key developments in nineteenth- and twentieth-century Europe, from the liberalism of the Latin American revolutions of the 1820s to the economic impact of the cotton-growing slave economies of the American south. The globalization processes of the late twentieth century have brought these into sharper focus and powered an approach that places Europe’s history in a broader global context of mutual interaction. Yet the nation-state is not dead, and national governments are vigorously promoting a return to national histories in the service of patriotic education. Global history is here to stay, but its place in the educational system, particularly school curricula, remains heavily contested.
Neonatal visual assessment in congenital heart disease: A pilot study
Authors: Feldmann Maria , Hagmann Cornelia , Bernet Vera , Knirsch Walter , Latal Beatrice
Published: August 2022

This study assessed neonatal visual maturity in infants with congenital heart disease (CHD) and its predictive value for neurodevelopmental outcomes. Neonates with CHD underwent a standardized visual assessment before and after cardiopulmonary bypass surgery. Visual maturity was rated as normal versus abnormal by means of normative reference data. Twelve-month neurodevelopment was assessed with the Bayley-III. Twenty-five healthy controls served as the reference group. Neonatal visual assessment was performed in five neonates with CHD preoperatively and in 24 postoperatively. Only postoperative assessments were considered for further analysis. Median [IQR] age at assessment was 27.0 [21.5, 42.0] days of life in postoperative neonates with CHD and 24.0 [15.0, 32.0] in controls. Visual performance was within reference values in 87.5% in postoperative CHD versus 90.5% in healthy controls (p = 1.0). Visual maturity was not predictive of neurodevelopment at 12 months. These results demonstrate the limited feasibility and predictive value of neonatal visual assessments in CHD.
Simulation-based study of turbulent aquatic canopy flows with flexible stems
Authors: He Sida , Liu Han , Shen Lian
Published: August 2022

Large-eddy simulation (LES) is performed to investigate the dynamics of flow and canopy motions and the energy transfer in turbulent canopy flows. Different from the traditional approach that models the canopy as a continuous medium with a drag coefficient prescribed a priori, an immersed boundary method together with a beam model is employed to explicitly capture the dynamics of individual stems and resolve monami. The simulation cases cover a broad range of stem flexibilities from rigid stems to oscillatory stems to stems yielding to the flow. For highly flexible canopies, the stem fluctuation is small such that the canopy behaves like a rigid canopy, which is used to explain the similarities of the flow features between rigid and highly flexible canopies. Analyses of the turbulent kinetic energy (TKE) budget show that, in the flexible canopy cases, the waving term associated with the canopy drag–flow velocity correlation can be as large as one-half of the shear production term near the canopy top. Spectral TKE budget analyses further reveal dominant effects at two characteristic scales: the monami scale associated with the coherent structures in the mixing layer and the wake scale associated with the interval between adjacent stems. For the TKE in flexible canopies, the waving term is found to play an important role in the interscale and wall-normal transport terms. Our LES data show that the spectral shortcut mechanism proposed by previous studies is caused by the waving term.
Optimal redundancy allocation in coherent systems with heterogeneous dependent components
Authors: Kelkinnama Maryam , Asadi Majid
Published: August 2022

This paper is concerned with the optimal number of redundant allocation ton-component coherent systems consisting of heterogeneous dependent components. We assume that the system is built up ofLgroups of different components,$L\geq 1$, where there are$n_i$components in groupi, and$\sum_{i=1}^{L}n_i=n$. The problem of interest is to allocate$v_i$active redundant components to each component of typei,$i=1,\dots, L$. To get the optimal values of$v_i$we propose two cost-based criteria. One of them is introduced based on the costs of renewing the failed components and the costs of refreshing the alive ones at the system failure time. The other criterion is proposed based on the costs of replacing the system at its failure time or at a predetermined time$\tau$, whichever occurs first. The expressions for the proposed functions are derived using the mixture representation of the system reliability function based on the notion of survival signature. We assume that a given copula function models the dependency structure between the components. In the particular case that the system is a series-parallel structure, we provide the formulas for the proposed cost-based functions. The results are discussed numerically for some specific coherent systems.
THE SECOND SHIFTED DIFFERENCE OF PARTITIONS AND ITS APPLICATIONS
Authors: GOMEZ KEVIN , MALES JOSHUA , ROLEN LARRY
Published: August 2022

A number of recent papers have estimated ratios of the partition function
$p(n-j)/p(n)$
, which appear in many applications. Here, we prove an easy-to-use effective bound on these ratios. Using this, we then study the second shifted difference of partitions,
$f(\,j,n) := p(n) -2p(n-j) +p(n-2j)$
, and give another easy-to-use estimate of
$f(\,j,n)$
. As applications of these, we prove a shifted convexity property of
$p(n)$
, as well as giving new estimates of the k-rank partition function
$N_k(m,n)$
and non-k-ary partitions along with their differences.
Barriers to consumption of fruits and vegetables and strategies to overcome them in low- and middle-income countries: a narrative review
Authors: Kaur Sukhdeep
Published: August 2022

This review provides an overview of the barriers to the consumption of fruits and vegetables (FVs) as well as strategies to improve the intake of FVs in low- and middle-income countries (LMICs). The importance of the consumption of FVs and its role in disease prevention are discussed briefly. Trends in the consumption of FVs in LMICs are also summarised. The WHO recommends that every individual should consume at least five servings or 400 grams of FVs per day. Epidemiological and clinical investigations have demonstrated that FVs contain numerous bioactive compounds with health-protecting activities. Despite their health benefits, the intake of FVs in LMICs remains low. Major barriers identified were socio-demographic factors, environmental conditions, individual and cultural factors, and macrosystem influences. These barriers may be lowered at the household, school, community, and national level through multi-component interventions including behaviour change communication (BCC) initiatives, nutrition education (NE), gardening initiatives, farm to institution programs (FIPs), food baskets, cash transfers, nutrition–agriculture policy and program linkages, and food-market environment-based strategies. This review has research implications due to the positive outcomes of strategies that lower such barriers and boost consumption of FVs in LMICs.
Ein Blick in die Glaskugel
Authors: Nienaber André , Reichel Anja Maria , Schulz Michael
Published: August 2022

Was ist zu dem Thema bekannt?

An unterschiedlichen Stellen werden Überlegungen zur Zukunft der psychiatrischen Versorgung angestellt und auch formuliert. Dies geschieht auch vor dem Hintergrund allgemeiner gesellschaftlicher und politischer Entwicklungen wie z.B. dem demografischen Wandel, Bildung, Armut etc.

Wie wird eine neue Perspektive eingebracht?

In diesem Artikel wird versucht einen Überblick über die Erkenntnisse aus der Literatur zu geben und diese Ergebnisse zusammenzufassen. Diese Zusammenfassung kann eine Grundlage für weitere und auch weiterführende Überlegungen im Hinblick auf die zukünftige psychiatrische Versorgung bilden.

Was sind die Auswirkungen auf die Praxis?

Zu den möglichen Auswirkungen auf die Praxis soll an dieser Stelle vor allem die Förderung und Unterstützung der Auseinandersetzung mit dem Thema der zukünftigen psychiatrischen und psychiatrisch-pflegerischen Versorgung genannt werden. Durch den Artikel kann eine kritisch-konstruktive Diskussion über Chancen und Herausforderungen der psychiatrischen Versorgung auf unterschiedlichen Ebenen angeregt und angestossen werden.
Interpretable Deep Learning for Probabilistic MJO Prediction
Authors: Delaunay Antoine , Christensen Hannah M.
Published: August 2022

The Madden‐Julian oscillation (MJO) is the dominant source of sub‐seasonal variability in the tropics. It consists of an Eastward moving region of enhanced convection coupled to changes in zonal winds. It is not possible to predict the precise evolution of the MJO, so sub‐seasonal forecasts are generally probabilistic. We present a deep convolutional neural network (CNN) that produces skilful state‐dependent probabilistic MJO forecasts. Importantly, the CNN's forecast uncertainty varies depending on the instantaneous predictability of the MJO. The CNN accounts for intrinsic chaotic uncertainty by predicting the standard deviation about the mean, and model uncertainty using Monte‐Carlo dropout. Interpretation of the CNN mean forecasts highlights known MJO mechanisms, providing confidence in the model. Interpretation of forecast uncertainty indicates mechanisms governing MJO predictability. In particular, we find an initially stronger MJO signal is associated with more uncertainty, and that MJO predictability is affected by the state of the Walker Circulation.
West Antarctic Surface Climate Changes Since the Mid‐20th Century Driven by Anthropogenic Forcing
Authors: Dalaiden Quentin , Schurer Andrew P. , Kirchmeier‐Young Megan C. , Goosse Hugues , Hegerl Gabriele C.
Published: August 2022

Although the West Antarctic surface climate has experienced large changes over the past decades with widespread surface warming, an overall increase in snow accumulation and a deepening of the Amundsen Sea Low, the exact role of human activities in these changes has not yet been fully investigated, which limits confidence in future projections. Here, we perform a detection and attribution analysis using instrumental and proxy‐based reconstructions, and two large climate model simulation ensembles to quantify the forced response in these observed changes. We show that surface climate changes since the 1950s were driven by anthropogenic forcing, in particular the greenhouse gas forcing and stratospheric ozone depletion. Therefore, our results indicate that the 21st century changes will depend on both the greenhouse gas emissions and the ozone layer recovery.
Rapid Healing of Thermal Cracks in Ice
Authors: Murdza Andrii , Schulson Erland M. , Renshaw Carl E. , Polojärvi Arttu
Published: August 2022

The structural integrity of the arctic sea ice cover is under threat owing largely to the combination of thinning and larger waves. Another contributor may be thermal cracking. In concentrating stress, thermal cracks may weaken the cover. Of interest, therefore, is the strength of thermally damaged ice. To that end, new experiments were performed on sea ice and on lab‐grown saline and salt‐free ice that had been cracked by thermal shocking. As expected, the cracks weakened the materials in accord with fracture mechanics. However, within tens to hundreds of seconds of shocking, the strength recovered completely, for the ice had healed. Healing is attributed to thermally activated sintering related to surface diffusion, assisted possibly by the formation of a quasi‐liquid layer on crack faces. Whether behavior on the small scale is indicative of behavior on the large scale remains to be determined.
Distinct Upward Propagation of the Westerly QBO in Winter 2015/16 and Its Relationship With Brewer‐Dobson Circulation
Authors: Kang Min‐Jee , Son Seok‐Woo , Chun Hye‐Yeong
Published: August 2022

A westerly phase of the quasi‐biennial oscillation (QBO) was disrupted in 2015/16. Previous studies have primarily focused on the cause of the localized negative momentum forcing, initiating the QBO disruption. However, the upward displacement of the westerly QBO followed by the negative momentum forcing, clearly observed in 2015/16, has received less attention. This study shows that the distinct upward propagation of the westerly winds during the 2015/16 QBO disruption was contributed by the strong Brewer‐Dobson circulation (BDC). Strong Rossby waves with wavenumber 1 propagating from the troposphere mainly drove the strong BDC. Potential contributions of El Niño and Barents–Kara sea ice reduction to Rossby waves are also discussed.
Seismic Evidence for a Weakened Thick Crust at the Beaufort Sea Continental Margin
Authors: Estève C. , Liu Y. , Koulakov I. , Schaeffer A. J. , Audet P.
Published: August 2022

The Canadian Beaufort Sea continental margin of northwestern Canada is a Cenozoic convergent margin, potentially representing a rare case of incipient subduction. Here, we produce P‐ and S‐wave seismic velocity models of the crust and the uppermost mantle using recordings from regional earthquakes. Our models reveal a northwest‐dipping very low‐velocity anomaly within the crust (δV up to −15%) beneath the Romanzof Uplift. We interpret this low‐velocity feature to correspond to a weaker and thicker crust due to shortening and stacking of igneous and sedimentary rocks. The co‐location of the thickened crust and lack of present‐day seismicity indicates that north‐south compression is accommodated by slow, aseismic deformation in the narrow margin beneath the Romanzof Uplift or more broadly offshore. Neither interpretation requires nor precludes a subduction initiation process.
Latent Heating Is Required for Firestorm Plumes to Reach the Stratosphere
Authors: Tarshish Nathaniel , Romps David M.
Published: August 2022

City‐wide firestorms produce extreme convective plumes that loft soot into the atmosphere. If emplaced in the stratosphere, soot has long‐lasting impacts on global climate. Given the extreme sensible heating from the fire, the importance of additional heating from condensation is unclear and a subject of debate. Analytic plume calculations presented here establish that an idealized dry plume requires a temperature anomaly of at least 60 K at the top of the boundary‐layer to remain buoyant up to the cold‐point tropopause. Direct numerical and large‐eddy simulations indicate that dry firestorm plumes possess temperature anomalies that are less than the requirements for stratospheric ascent by a factor of two or more. In contrast, moist firestorm plumes are shown to reach the stratosphere by tapping into the abundant latent heat present in a moist environment. Latent heating is found to be essential to plume rise, raising doubts about the applicability of past work that neglected moisture.
Combinatorial treatment with statins and niclosamide prevents CRC dissemination by unhinging the MACC1-β-catenin-S100A4 axis of metastasis
Authors: Kortüm Benedikt , Radhakrishnan Harikrishnan , Zincke Fabian , Sachse Christoph , Burock Susen , Keilholz Ulrich , Dahlmann Mathias , Walther Wolfgang , Dittmar Gunnar , Kobelt Dennis , Stein Ulrike
Published: August 2022

Colorectal cancer (CRC) is the second-most common malignant disease worldwide, and metastasis is the main culprit of CRC-related death. Metachronous metastases remain to be an unpredictable, unpreventable, and fatal complication, and tracing the molecular chain of events that lead to metastasis would provide mechanistically linked biomarkers for the maintenance of remission in CRC patients after curative treatment. We hypothesized, that Metastasis-associated in colorectal cancer-1 (MACC1) induces a secretory phenotype to enforce metastasis in a paracrine manner, and found, that the cell-free culture medium of MACC1-expressing CRC cells induces migration. Stable isotope labeling by amino acids in cell culture mass spectrometry (SILAC-MS) of the medium revealed, that S100A4 is significantly enriched in the MACC1-specific secretome. Remarkably, both biomarkers correlate in expression data of independent cohorts as well as within CRC tumor sections. Furthermore, combined elevated transcript levels of the metastasis genes MACC1 and S100A4 in primary tumors and in blood plasma robustly identifies CRC patients at high risk for poor metastasis-free (MFS) and overall survival (OS). Mechanistically, MACC1 strengthens the interaction of β-catenin with TCF4, thus inducing S100A4 synthesis transcriptionally, resulting in elevated secretion to enforce cell motility and metastasis. In cell motility assays, S100A4 was indispensable for MACC1-induced migration, as shown via knock-out and pharmacological inhibition of S100A4. The direct transcriptional and functional relationship of MACC1 and S100A4 was probed by combined targeting with repositioned drugs. In fact, the MACC1-β-catenin-S100A4 axis by statins (MACC1) and niclosamide (S100A4) synergized in inhibiting cancer cell motility in vitro and metastasis in vivo. The MACC1-β-catenin-S100A4 signaling axis is causal for CRC metastasis. Selectively repositioned drugs synergize in restricting MACC1/S100A4-driven metastasis with cross-entity potential.
A high-throughput drug screen reveals means to differentiate triple-negative breast cancer
Authors: Vulin Milica , Jehanno Charly , Sethi Atul , Correia Ana Luísa , Obradović Milan M. S. , Couto Joana Pinto , Coissieux Marie-May , Diepenbruck Maren , Preca Bogdan-Tiberius , Volkmann Katrin , der Maur Priska Auf , Schmidt Alexander , Münst Simone , Sauteur Loïc , Kloc Michal , Palafox Marta , Britschgi Adrian , Unterreiner Vincent , Galuba Olaf , Claerr Isabelle , Lopez-Romero Sandra , Galli Giorgio G. , Baeschlin Daniel , Okamoto Ryoko , Soysal Savas D. , Mechera Robert , Weber Walter P. , Radimerski Thomas , Bentires-Alj Mohamed
Published: August 2022

Plasticity delineates cancer subtypes with more or less favourable outcomes. In breast cancer, the subtype triple-negative lacks expression of major differentiation markers, e.g., estrogen receptor α (ERα), and its high cellular plasticity results in greater aggressiveness and poorer prognosis than other subtypes. Whether plasticity itself represents a potential vulnerability of cancer cells is not clear. However, we show here that cancer cell plasticity can be exploited to differentiate triple-negative breast cancer (TNBC). Using a high-throughput imaging-based reporter drug screen with 9 501 compounds, we have identified three polo-like kinase 1 (PLK1) inhibitors as major inducers of ERα protein expression and downstream activity in TNBC cells. PLK1 inhibition upregulates a cell differentiation program characterized by increased DNA damage, mitotic arrest, and ultimately cell death. Furthermore, cells surviving PLK1 inhibition have decreased tumorigenic potential, and targeting PLK1 in already established tumours reduces tumour growth both in cell line- and patient-derived xenograft models. In addition, the upregulation of genes upon PLK1 inhibition correlates with their expression in normal breast tissue and with better overall survival in breast cancer patients. Our results indicate that differentiation therapy based on PLK1 inhibition is a potential alternative strategy to treat TNBC.
Patient trajectories after diagnosis of diffuse large B-cell lymphoma—a multistate modelling approach to estimate the chance of lasting remission
Authors: Ekberg Sara , Crowther Michael , Harrysson Sara , Jerkeman Mats , E. Smedby Karin , Eloranta Sandra
Published: August 2022

Background

Achieving lasting remission for at least 2 years is a good indicator for favourable prognosis long term after Diffuse large B-cell lymphoma (DLBCL). The aim of this study was to provide real-world probabilities, useful in risk communication and clinical decision-making, of the chance for lasting remissions by clinical characteristics.

Methods

DLBCL patients in remission after primary treatment recorded in the Swedish Lymphoma register 2007–2014 (n = 2941) were followed for relapse and death using multistate models to study patient trajectories. Flexible parametric models were used to estimate transition rates.

Results

At 2 years, 80.7% (95% CI: 79.0–82.2) of the patients were predicted to remain in remission and 13.2% (95% CI: 11.9–14.6) to have relapsed. The relapse risk peaked at 7 months, and the annual decline of patients in remission stabilised after 2 years. The majority of patients in the second remission transitioned into a new relapse. The probability of a lasting remission was reduced by 20.4% units for patients with IPI 4–5 compared to patients with IPI 0–1, and time in remission was shortened by 3.5 months.

Conclusion

The long-term prognosis was overall favourable with 80% achieving durable first remissions. However, prognosis varied by clinical subgroups and relapsing patients seldom achieved durable second remissions.
Circular RNA hsa_circ_0007367 promotes the progression of pancreatic ductal adenocarcinoma by sponging miR-6820-3p and upregulating YAP1 expression
Authors: Zhang Haocheng , Ma Xiaolei , Wang Luning , Li Xinyu , Feng Di , Liu Meiming , Li Jiayang , Cheng Mengxing , Song Na , Yang Xinxia , Ba Lina , Lei Yating , Zhang Ruipu , Zhu Yunxiao , Xu Wenxiao , Qiao Guofen
Published: August 2022

Circular RNAs (circRNAs) play critical regulatory roles in cancer biological processes. Nevertheless, the contributions and underlying mechanisms of circRNAs to pancreatic ductal adenocarcinoma (PDAC) remain largely unexplored. Dysregulated circRNAs between cancerous tissues and matched adjacent normal tissues were identified by circRNA microarray in PDAC. The biological effect of hsa_circ_007367 both in vitro and in vivo was demonstrated by gain- and loss-of-function experiments. Further, dual-luciferase reporter and RNA pull-down assays were performed to confirm the interaction among hsa_circ_007367, miR-6820-3p, and Yes-associated protein 1 (YAP1). The expression of hsa_circ_007367 and YAP1 were detected by in situ hybridization (ISH) and immunohistochemistry (IHC) using tissue microarray (TMA) in 128 PDAC samples. We first identified that a novel circRNA, hsa_circ_0007367, was markedly upregulated in PDAC tissues and cells. Functionally, in vivo and in vitro data indicated that hsa_circ_0007367 promotes the proliferation and metastasis of PDAC. Mechanistically, we confirmed that hsa_circ_0007367 could facilitate the expression of YAP1, a well-known oncogene, by sponging miR-6820-3p, which function as a tumor suppresser in PDAC cells. The results of ISH and IHC demonstrated that hsa_circ_0007367 and YAP1 were upregulated in PDAC tissues. Furthermore, clinical data showed that higher hsa_circ_0007367 expression was correlated with advanced histological grade and lymph node metastasis in PDAC patients. In conclusion, our findings reveal that hsa_circ_0007367 acts as an oncogene via modulating miR-6820-3p/YAP1 axis to promote the progression of PDAC, and suggest that hsa_circ_0007367 may serve as a potential therapeutic target for treatment of PDAC.
The microRNA-10b-Bim axis promotes cancer progression through activating autophagy in oral squamous cell carcinoma
Authors: Li Shaoming , Gao Ling , Liu Jiacheng , Guo Chao , Zheng Jingjing , Zhi Keqian , Ren Wenhao
Published: August 2022

Autophagy is related to many cellular mechanisms and dysregulation of autophagy involves the pathological process in cancer. miR-10b activates autophagy, which promotes invasion and migration of OSCC. Its functional role in the mechanism of OSCC to autophagy remains to be unclear. Overexpression of miR-10b was followed by enhanced OSCC invasion and migration and activated autophagic protein, such as LC3II/ATG5. MiR-10b attracted Bim directly according to the Bio-informatics analyses and double luciferases reporter assays. Functional experiments further revealed that miR-10b could promote invasion and migration in vitro. In addition, miR-10b induced autophagy via inhibiting Bim in invasion and migration of OSCC. Notably, animal experiments confirmed that miR-10b-Bim promoted proliferation and autophagy in OSCC. In addition, this study provides a theoretical support for regulating the mechanism of OSCC by inducing autophagy with miR-10b-Bim as a target.
Cholinergic basal forebrain nucleus of Meynert regulates chronic pain-like behavior via modulation of the prelimbic cortex
Authors: Oswald Manfred J. , Han Yechao , Li Han , Marashli Samuel , Oglo Deniz Nouri , Ojha Bhavya , Naser Paul V. , Gan Zheng , Kuner Rohini
Published: August 2022

The basal nucleus of Meynert (NBM) subserves critically important functions in attention, arousal and cognition via its profound modulation of neocortical activity and is emerging as a key target in Alzheimer’s and Parkinson’s dementias. Despite the crucial role of neocortical domains in pain perception, however, the NBM has not been studied in models of chronic pain. Here, using in vivo tetrode recordings in behaving mice, we report that beta and gamma oscillatory activity is evoked in the NBM by noxious stimuli and is facilitated at peak inflammatory pain-like behavior. Optogenetic and chemogenetic cell-specific, reversible manipulations of NBM cholinergic-GABAergic neurons reveal their role in endogenous control of nociceptive hypersensitivity, which are manifest via projections to the prelimbic cortex, resulting in layer 5-mediated antinociception. Our data unravel the importance of the NBM in top-down control of neocortical processing of pain-like behavior.
An interplay between cellular growth and atypical fusion defines morphogenesis of a modular glial niche in Drosophila
Authors: Rujano Maria Alexandra , Briand David , Ðelić Bojana , Marc Julie , Spéder Pauline
Published: August 2022

Neural stem cells (NSCs) live in an intricate cellular microenvironment supporting their activity, the niche. Whilst shape and function are inseparable, the morphogenetic aspects of niche development are poorly understood. Here, we use the formation of a glial niche to investigate acquisition of architectural complexity. Cortex glia (CG) in Drosophila regulate neurogenesis and build a reticular structure around NSCs. We first show that individual CG cells grow tremendously to ensheath several NSC lineages, employing elaborate proliferative mechanisms which convert these cells into syncytia rich in cytoplasmic bridges. CG syncytia further undergo homotypic cell–cell fusion, using defined cell surface receptors and actin regulators. Cellular exchange is however dynamic in space and time. This atypical cell fusion remodels cellular borders, restructuring the CG syncytia. Ultimately, combined growth and fusion builds the multi-level architecture of the niche, and creates a modular, spatial partition of the NSC population. Our findings provide insights into how a niche forms and organises while developing intimate contacts with a stem cell population.