bluuebunny/crossref_metadata_2025_split huggingface dataset:
Toward interpretable digital biomarkers of walking and reaching in Parkinson’s disease
Authors: Ryu Jihye , Torres Elizabeth 
Published: September 2022

Abstract
Multimodal digital data registered with wearable biosensors have emerged as highly complementary of clinical pencil-and-paper criteria, offering new insights in ways to detect and diagnose various aspects of Parkinson’s disease (PD). A pressing question is how to combine both the clinical knowledge of PD and the new technology to create interpretable digital biomarkers easily obtainable with off-the-shelf technology. Several challenges concerning disparity in biophysical units, anatomical differences across participants, sensor positioning, and sampling resolution are addressed in this work, along with identification of optimal parameters to automatically differentiate patients with PD from controls. We combine data from a multitude of biosensors registering signals from the central (electroencephalography) and peripheral (magnetometry, kinematics) nervous systems, inclusive of the autonomic nervous system (electrocardiogram), as the participants perform natural tasks requiring different levels of intentional planning and automatic control. We find that magnetometer data during walking, across a variety of amplitude and timing signals, provide optimal separation of PD from neurotypical controls. We conclude that using multimodal signals within the context of actions that bear different levels of intent, can be revealing of features of PD that would scape the naked eye. Further, we add that clinical criteria combined with such optimal digital parameter spaces offer a far more complete picture of PD than using either one of these pieces of data alone.
Using Ice Cores to Evaluate CMIP6 Aerosol Concentrations Over the Historical Era
Authors: Moseid Kine Onsum , Schulz Michael , Eichler Anja , Schwikowski Margit , McConnell Joseph R. , Olivié Dirk , Criscitiello Alison S. , Kreutz Karl J. , Legrand Michel 
Published: September 2022

AbstractThe radiative effect of anthropogenic aerosols is one of the largest uncertainties in Earth's energy budget over the industrial period. This uncertainty is in part due to sparse observations of aerosol concentrations in the pre‐satellite era. To address this lack of measurements, ice cores can be used, which contain the aerosol concentration record. To date, these observations have been under‐utilized for comparison to aerosol concentrations found in state‐of‐the‐art Earth system models (ESMs). Here we compare long term trends in concentrations of sulfate and black carbon (BC) between 15 ice cores and 11 ESMs over nine regions around the world during the period 1850–2000. We find that for sulfate concentration trends model results generally agree with ice core records, whereas for BC concentration the model trends differ from the records. Absolute concentrations of both investigated species are overestimated by the models, probably in part due to representation errors. However, we assume that biases in relative trends are not altered by these errors. Ice cores in the European Alps and Greenland record a maximum BC concentration before 1950, while most ESMs used in this study agree on a post‐1950 maximum. We source this bias to an error in BC emission inventories in Europe. Emission perturbation experiments using NorESM2‐LM support the observed finding that BC concentrations in Northern Greenland ice cores are recording European emissions. Errors in BC emission inventories have implications for all future and past studies where Coupled Model Intercomparison Project Phase 6 historical simulations are compared to observations relevant to aerosol forcing.
Which Sudden Stratospheric Warming Events Are Most Predictable?
Authors: Chwat Dvir , Garfinkel Chaim I. , Chen Wen , Rao Jian 
Published: September 2022

AbstractThe predictability of Northern Hemisphere sudden stratospheric warming (SSW) events is considered in 10 subseasonal to seasonal (S2S) forecast models for 16 major SSWs that have occurred since 1998, a larger sample size than has been considered by previous works. The four factors that most succinctly distinguish those SSWs with above average predictability are a preconditioned vortex prior to the SSW, an active Madden‐Julian Oscillation with enhanced convection in the West Pacific, the Quasi‐Biennial Oscillation phase with easterlies in the lower stratosphere, and the vortex morphology (displacement more predictable). Two of these factors appear to not have been considered in previous works focusing on a large sample of events. Most of these effects are not statistically significant at the 95% level due to the still relatively small sample size, though all would exceed a 90% criteria at least marginally. Combined, however, they account for 40% of the inter‐event spread in SSW predictability, thus indicating that SSWs with favorable precursors are significantly more predictable.
Tumor-derived exosomes deliver the tumor suppressor miR-3591-3p to induce M2 macrophage polarization and promote glioma progression
Authors: Li Ming , Xu Hao , Qi Yanhua , Pan Ziwen , Li Boyan , Gao Zijie , Zhao Rongrong , Xue Hao , Li Gang 
Published: September 2022

AbstractExosomes can selectively secrete harmful metabolic substances from cells to maintain cellular homeostasis, and complex crosstalk occurs between exosomes and tumor-associated macrophages (TAMs) in the glioma immune microenvironment. However, the precise mechanisms by which these exosome-encapsulated cargos create an immunosuppressive microenvironment remain unclear. Herein, we investigated the effect of glioma-derived exosomes (GDEs) on macrophage polarization and glioma progression. We performed sequencing analysis of cerebrospinal fluid (CSF) and tumor tissues from glioma patients to identify functional microRNAs (miRNAs). High levels of miR-3591-3p were found in CSF and GDEs but not in normal brain tissue or glial cells. Functionally, GDEs and miR-3591-3p significantly induced M2 macrophage polarization and increased the secretion of IL10 and TGFβ1, which in turn promoted glioma invasion and migration. Moreover, miR-3591-3p overexpression in glioma cell lines resulted in G2/M arrest and markedly increased apoptosis. Mechanistically, miR-3591-3p can directly target CBLB and MAPK1 in macrophages and glioma cells, respectively, and further activate the JAK2/PI3K/AKT/mTOR, JAK2/STAT3, and MAPK signaling pathways. In vivo experiments confirmed that macrophages lentivirally transduced with miR-3591-3p can significantly promote glioma progression. Thus, our study demonstrates that tumor-suppressive miR-3591-3p in glioma cells can be secreted via exosomes and target TAMs to induce the formation of an immunosuppressive microenvironment. Collectively, these findings provide new insights into the role of glioma exosomal miRNAs in mediating the establishment of an immunosuppressive tumor microenvironment and show that miR-3591-3p may be a valuable biomarker and that blocking the encapsulation of miR-3591-3p into exosomes may become a novel immunotherapeutic strategy for glioma.
Decolonisation of curricula in undergraduate dental education: an exploratory study
Authors: Ali Kamran , Winter Jennie , Webb Oliver , Zahra Daniel 
Published: September 2022

AbstractAims To explore experiences and perceptions of students and staff regarding decolonisation of the curriculum in a dental undergraduate programme.Methods Participants were invited to respond to an online survey on decolonisation of the dental curriculum. The target population included current students on the Bachelor of Dental Surgery and Bachelor of Dental Therapy and Hygiene programmes, as well as dental staff at a university in the South West region of England. The common items for student and staff versions of the survey were focused on six themes: representation; content; peer engagement; assessment; language and communication; and culture. All responses were anonymous. Data on programme, year of study, age, sex and ethnicity were captured on a voluntary basis.Results In total, 34 staff members and 120 students from two different programmes participated in the survey, yielding a response rate of 87.17% for staff and 45.28% for students. A comparison showed that average student responses were lower compared with average staff responses. Of the 24 survey items, 17 showed significantly lower scores reported by minority ethnic (ME) students. ME students were, when compared with white counterparts, less likely to report that their programme included opportunities for group discussions about ethnicity and privilege. Similar comparisons of staff responses did not show significant differences between white and ME staff. Nevertheless, responses by staff and students across the board highlighted the need for further steps to improve the representation of ME groups in the curriculum.Conclusions This study provides useful insights into the perceptions and experiences of students and staff regarding the decolonisation of the dental curriculum in an undergraduate dental programme. Responses by the participants across the board identified several areas which could benefit from better representation of ME groups. Significant differences were noted between staff and student scores and also between white and ME students, indicating the latter group demonstrated more awareness regarding issues of representation. The findings underscore the need to take further steps to decolonise dental curricula.
Deubiquitinase OTUD5 modulates mTORC1 signaling to promote bladder cancer progression
Authors: Hou Tao , Dan Weichao , Liu Tianjie , Liu Bo , Wei Yi , Yue Chenyang , Que Taotao , Ma Bohan , Lei Yuzeshi , Wang Zixi , Zeng Jin , Fan Yizeng , Li Lei 
Published: September 2022

AbstractThe mechanistic (formally “mammalian”) target of rapamycin (mTOR) pathway serves as a crucial regulator of various biological processes such as cell growth and cancer progression. In bladder cancer, recent discoveries showing the cancer-promoting role of mTOR complex 1 have attracted wide attention. However, the regulation of mTOR signaling in bladder cancer is complicated and the underlying mechanism remains elusive. Here, we report that the deubiquitinating enzyme, ovarian tumor domain-containing protein 5 (OTUD5), can activate the mTOR signaling pathway, promote cancer progression, and show its oncogenic potential in bladder cancer. In our study, we found that OTUD5 deubiquitinated a RING-type E3 ligase, RNF186, and stabilized its function. In addition, the stabilization of RNF186 further led to the degradation of sestrin2, which is an inhibitor of the mTOR signaling pathway. Together, we provide novel insights into the pathogenesis of bladder cancer and first prove that OTUD5 can promote bladder cancer progression through the OTUD5-RNF186-sestrin2-mTOR axis, which may be exploited in the future for the diagnosis and treatment of this malignancy.
Front-of-pack nutrition labels: an equitable public health intervention
Authors: Pettigrew Simone , Jongenelis Michelle I. , Hercberg Serge , Julia Chantal 
Published: September 2022

AbstractIt is important for nutrition interventions to be equitable to ensure they do not widen socioeconomic health-based inequalities. The role of front-of-pack nutrition labels is to provide accessible and easily understood information on product packages, and it is essential that such labels assist those who are least able to access and interpret other forms of nutrition information. This secondary analysis of the FOP-ICE food labelling study involving 18 countries (N = 18,393) assessed whether five different front-of-pack labels varied in effectiveness according to income status. The two outcome variables were objective understanding of products’ nutritional quality and product choice. While there were substantial differences in the ability of individual labels to improve understanding, for each label and across all labels combined there were no significant differences in changes in both outcome variables by income category. The results provide evidence that interpretive front-of-pack nutrition labels are an equitable and useful nutrition intervention.
Quantum nonlinear spectroscopy of single nuclear spins
Authors: Meinel Jonas , Vorobyov Vadim , Wang Ping , Yavkin Boris , Pfender Mathias , Sumiya Hitoshi , Onoda Shinobu , Isoya Junichi , Liu Ren-Bao , Wrachtrup J. 
Published: September 2022

AbstractConventional nonlinear spectroscopy, which use classical probes, can only access a limited set of correlations in a quantum system. Here we demonstrate that quantum nonlinear spectroscopy, in which a quantum sensor and a quantum object are first entangled and the sensor is measured along a chosen basis, can extract arbitrary types and orders of correlations in a quantum system. We measured fourth-order correlations of single nuclear spins that cannot be measured in conventional nonlinear spectroscopy, using sequential weak measurement via a nitrogen-vacancy center in diamond. The quantum nonlinear spectroscopy provides fingerprint features to identify different types of objects, such as Gaussian noises, random-phased AC fields, and quantum spins, which would be indistinguishable in second-order correlations. This work constitutes an initial step toward the application of higher-order correlations to quantum sensing, to examining the quantum foundation (by, e.g., higher-order Leggett-Garg inequality), and to studying quantum many-body physics.
Targeted immunotherapy against distinct cancer-associated fibroblasts overcomes treatment resistance in refractory HER2+ breast tumors
Authors: Rivas Elisa I. , Linares Jenniffer , Zwick Melissa , Gómez-Llonin Andrea , Guiu Marc , Labernadie Anna , Badia-Ramentol Jordi , Lladó Anna , Bardia Lídia , Pérez-Núñez Iván , Martínez-Ciarpaglini Carolina , Tarazona Noelia , Sallent-Aragay Anna , Garrido Marta , Celià-Terrassa Toni , Burgués Octavio , Gomis Roger R. , Albanell Joan , Calon Alexandre 
Published: September 2022

AbstractAbout 50% of human epidermal growth factor receptor 2 (HER2)+ breast cancer patients do not benefit from HER2-targeted therapy and almost 20% of them relapse after treatment. Here, we conduct a detailed analysis of two independent cohorts of HER2+ breast cancer patients treated with trastuzumab to elucidate the mechanisms of resistance to anti-HER2 monoclonal antibodies. In addition, we develop a fully humanized immunocompetent model of HER2+ breast cancer recapitulating ex vivo the biological processes that associate with patients’ response to treatment. Thanks to these two approaches, we uncover a population of TGF-beta-activated cancer-associated fibroblasts (CAF) specific from tumors resistant to therapy. The presence of this cellular subset related to previously described myofibroblastic (CAF-S1) and podoplanin+ CAF subtypes in breast cancer associates with low IL2 activity. Correspondingly, we find that stroma-targeted stimulation of IL2 pathway in unresponsive tumors restores trastuzumab anti-cancer efficiency. Overall, our study underscores the therapeutic potential of exploiting the tumor microenvironment to identify and overcome mechanisms of resistance to anti-cancer treatment.
Intrinsic hard magnetism and thermal stability of a ThMn12-type permanent magnet
Authors: Ochirkhuyag Tumentsereg , Hong Soon Cheol , Odkhuu Dorj 
Published: September 2022

AbstractHerein, we theoretically demonstrate that simple metal (Ga and Al) substitutional atoms, rather than the conventional transition metal substitutional elements, not only stabilize the ThMn12-type SmFe12 and Sm(Fe,Co)12 phases thermodynamically but also further improve their intrinsic magnetic properties such that they are superior to those of the widely investigated SmFe11Ti and Sm(Fe,Co)11Ti magnets, and even to the state-of-the-art permanent magnet Nd2Fe14B. More specifically, the quaternary Sm(Fe,Co,Al)12 phase has the highest uniaxial magnetocrystalline anisotropy (MCA) of about 8 MJ m−3, anisotropy field of 18.2 T, and hardness parameter of 2.8 at room temperature and a Curie temperature of 764 K. Simultaneously, the Al and Ga substitutional atoms improve the single-domain size of the Sm(Fe,Co)12 grains by nearly a factor of two. Numerical results of MCA and MCA-driven hard magnetic properties can be described by the strong spin-orbit coupling and orbital angular momentum of the Sm 4f-electron orbitals.
Predicting glass structure by physics-informed machine learning
Authors: Bødker Mikkel L. , Bauchy Mathieu , Du Tao , Mauro John C. , Smedskjaer Morten M. 
Published: September 2022

AbstractMachine learning (ML) is emerging as a powerful tool to predict the properties of materials, including glasses. Informing ML models with knowledge of how glass composition affects short-range atomic structure has the potential to enhance the ability of composition-property models to extrapolate accurately outside of their training sets. Here, we introduce an approach wherein statistical mechanics informs a ML model that can predict the non-linear composition-structure relations in oxide glasses. This combined model offers an improved prediction compared to models relying solely on statistical physics or machine learning individually. Specifically, we show that the combined model accurately both interpolates and extrapolates the structure of Na2O–SiO2 glasses. Importantly, the model is able to extrapolate predictions outside its training set, which is evidenced by the fact that it is able to predict the structure of a glass series that was kept fully hidden from the model during its training.
Solution-processable through-space charge-transfer emitters via solubilizing groups modification
Authors: Zheng Qi , Wang Xue-Qi , Qu Yang-Kun , Xie Guohua , Liao Liang-Sheng , Jiang Zuo-Quan 
Published: September 2022

AbstractThe solubility of luminescent materials is a key parameter to improve the electroluminescent performances of solution-processed organic light-emitting diodes (OLEDs). The through-space charge transfer (TSCT) materials provide an alternative to introduce the solubilizing groups (SGs) to the linker. Herein, thetert-butyl andn-hexyl groups are introduced as SGs at C7 positions of spiro structure, namedC6-DMBandtBu-DMB, away from the acceptor. This has no influence on the photophysical properties of the parent TSCT molecule. Highly efficient solution-processed OLEDs were demonstrated with the maximum external quantum efficiencies of 21.0% and 21.7%, respectively. To the best of our knowledge, these are champions in the state-of-the-art solution-processed OLEDs with TSCT emitters. This work confirmed our conjecture of constructing highly efficient soluble emitters by transforming an outstanding TSCT material from thermal evaporation to solution-processed OLEDs with SGs simply integrated on the ‘bridge’ linker.
Parallel InAs nanowires for Cooper pair splitters with Coulomb repulsion
Authors: Kürtössy Olivér , Scherübl Zoltán , Fülöp Gergő , Lukács István Endre , Kanne Thomas , Nygård Jesper , Makk Péter , Csonka Szabolcs 
Published: September 2022

AbstractHybrid nanostructures consisting of two parallel InAs nanowires connected by an epitaxially grown superconductor (SC) shell recently became available. Due to the defect-free SC-semiconductor interface and the two quasi-one-dimensional channels being close by, these platforms can be utilized to spatially separate entangled pairs of electrons by using quantum dots (QD) in the so-called Cooper pair splitting (CPS) process. The minimized distance between the QDs overcomes the limitations of single-wire-based geometries and can boost the splitting efficiency. Here we investigate CPS in such a device where strong inter-dot Coulomb repulsion is also present and studied thoroughly. We analyze theoretically the slight reduction of the CPS efficiency imposed by the Coulomb interaction and compare it to the experiments. Despite the competition between crossed Andreev reflection (CAR) and inter-wire capacitance, a significant CPS signal is observed indicating the dominance of the superconducting coupling. Our results demonstrate that the application of parallel InAs nanowires with epitaxial SC is a promising route for the realization of parafermionic states relying on enhanced CAR between the wires.
Myogenesis defects in a patient-derived iPSC model of hereditary GNE myopathy
Authors: Schmitt Rebecca E. , Smith Douglas Y. , Cho Dong Seong , Kirkeby Lindsey A. , Resch Zachary T. , Liewluck Teerin , Niu Zhiyv , Milone Margherita , Doles Jason D. 
Published: September 2022

AbstractHereditary muscle diseases are disabling disorders lacking effective treatments. UDP-N-acetylglucosamine-2-epimerase/N-acetylmannosamine kinase (GNE) myopathy (GNEM) is an autosomal recessive distal myopathy with rimmed vacuoles typically manifesting in late adolescence/early adulthood.GNEencodes the rate-limiting enzyme in sialic acid biosynthesis, which is necessary for the proper function of numerous biological processes. Outside of the causative gene, very little is known about the mechanisms contributing to the development of GNE myopathy. In the present study, we aimed to address this knowledge gap by querying the underlying mechanisms of GNE myopathy using a patient-derived induced pluripotent stem-cell (iPSC) model. Control and patient-specific iPSCs were differentiated down a skeletal muscle lineage, whereby patient-derived GNEM iPSC clones were able to recapitulate key characteristics of the human pathology and further demonstrated defects in myogenic progression. Single-cell RNA sequencing time course studies revealed clear differences between control and GNEM iPSC-derived muscle precursor cells (iMPCs), while pathway studies implicated altered stress and autophagy signaling in GNEM iMPCs. Treatment of GNEM patient-derived iMPCs with an autophagy activator improved myogenic differentiation. In summary, we report an in vitro, iPSC-based model of GNE myopathy and implicate defective myogenesis as a contributing mechanism to the etiology of GNE myopathy.
Evaluation of the causal relationship between smoking and schizophrenia in East Asia
Authors: Su Mei-Hsin , Lai Rou-Yi , Lin Yen-Feng , Chen Chia-Yen , Feng Yen-Chen A. , Hsiao Po-Chang , Wang Shi-Heng 
Published: September 2022

AbstractCigarette smoking has been suggested to be associated with the risk of schizophrenia in observational studies. A significant causal effect of smoking on schizophrenia has been reported in European populations using the Mendelian randomization approach; however, no evidence of causality was found in participants from East Asia. Using Taiwan Biobank (TWBB), we conducted genome-wide association studies (GWAS) to identify susceptibility loci for smoking behaviors, including smoking initiation (N = 79,989) and the onset age (N = 15,582). We then meta-analyzed GWAS from TWBB and Biobank Japan (BBJ) with the total sample size of 245,425 for smoking initiation and 46,000 for onset age of smoking. The GWAS for schizophrenia was taken from the East Asia Psychiatric Genomics Consortium, which included 22,778 cases and 35,362 controls. We performed a two-sample Mendelian randomization to estimate the causality of smoking behaviors on schizophrenia in East Asia. In TWBB, we identified one locus that met genome-wide significance for onset age. In a meta-analysis of TWBB and BBJ, we identified two loci for smoking initiation. In Mendelian randomization, genetically predicted smoking initiation (odds ratio (OR) = 4.00, 95% confidence interval (CI) = 0.89–18.01,P = 0.071) and onset age (OR for a per-year increase = 0.96, 95% CI = 0.91–1.01,P = 0.098) were not significantly associated with schizophrenia; the direction of effect was consistent with European Ancestry samples, which had higher statistical power. These findings provide tentative evidence consistent with a causal role of smoking on the development of schizophrenia in East Asian populations.