bluuebunny/crossref_metadata_2025_split huggingface dataset:
LMOOC research 2014 to 2021: What have we done and where are we going next?
Authors: Zhang Yining , Sun Ruoxi 
Published: January 2023

AbstractThis study reviews 71 high-quality studies of massive open online courses focused on languages (LMOOCs) that were published from the inception of LMOOCs to 2021. The purpose of this study is to gain a deeper understanding of the current state of research and identify fruitful directions for future LMOOC research. First, we reviewed three basic sets of characteristics of these studies: (1) research trends – for example, publication types and years; (2) research contexts – for example, countries in which the studies were conducted, the subjects’ target languages, language-ability levels, skills, and whether the focal courses are for specific purposes; and (3) research design, including data collection, data analysis, and theoretical frameworks. We then utilized a text-mining approach called Latent Dirichlet Allocation that uses machine-learning techniques to identify research-topic commonalities underlying the collected studies. In this way, a total of nine topics were identified. They were: (1) core elements of LMOOCs; (2) interaction and communication in LMOOCs; (3) innovative LMOOC teaching practices; (4) LMOOC standards and quality assurance; (5) LMOOC implementation, participation, and completion; (6) LMOOC teaching plans; (7) LMOOC learning effectiveness and its drivers/obstacles; (8) learners and learning in LMOOCs; and (9) inclusiveness in LMOOCs. These were then diagrammed as a ThemeRiver, which showed the evolutionary trend of the nine identified topics. Specifically, scholarly interest in Topics 5, 7, and 9 increased over time, whereas for Topics 1 and 6, it decreased. Based on our results, we highlighted specific directions for future LMOOC research on each of the identified research topics.
Biotherapeutic microbial supplementation for ameliorating fish health: developing trends in probiotics, prebiotics, and synbiotics use in finfish aquaculture
Authors: Puri Parul , Sharma Jai Gopal , Singh Ram 
Published: January 2023

AbstractNutrition demands in aquaculture can be realized through quality aquafeeds as compounded diets that contribute to the growth and health of aquaculture species. Functional additives in feed, notably probiotics, prebiotics, and their admixture synbiotics, have been recently recognized for their biotherapeutic role as immunostimulants capable of conferring disease resistance, stress tolerance, and gastrointestinal health; counteracting the negative effects of anti-nutrients, pathogenic prevalence, and antimicrobials in finfish aquaculture. Formulated diets based on probiotics, prebiotics, and as a supplemental combination for synbiotics can significantly influence fish gut microbiomes, establishing the modalities of microbial dynamics to maximize host-associated benefits. These microbial functional-feed supplements are acclaimed to be biocompatible, biodegradable, and safe for dietary consumption as well as the environment. In fed fish aquaculture, prebiotic appended probiotic diet ‘synbiotic’ has propounded larger attention for its additional health and nutritional benefits. Synbiotic, prebiotic, and probiotic usage as functional feeds for finfish aquaculture thus provides promising prospects. Developing trends in their intended application are reviewed here forth.
Understanding Peat Soil Deformation and Mechanisms of Peat Collapse Across a Salinity Gradient in the Southwestern Everglades
Authors: Sirianni Matthew J. , Comas Xavier , Mount Gregory J. , Pierce Shelley , Coronado‐Molina Carlos , Rudnick David 
Published: January 2023

AbstractSaltwater intrusion is a significant threat to the structure and ecology of inland and coastal freshwater wetlands, altering biogeochemical cycling and disrupting important ecosystem services. As sea level rises along the Florida coast, the saltwater interface progressively moves further inland reaching freshwater soils previously unexposed to saltwater. One result of this soil salinization is a phenomenon called peat collapse which is currently observable along the South Florida coastline. While previous studies have proposed conceptual models to explain peat collapse many uncertainties still exist regarding the physical mechanisms that trigger this phenomenon. In this study we use a unique combination of laboratory and field‐based measurements using geophysical methods, deformation rods, gas traps, time‐lapse photography, and hydraulic conductivity measurements to investigate the effects of salinization on the physical properties of peat soils across a salinity gradient in the southwestern Everglades. Our results show that freshwater peat soils have about three times greater degree of pore dilation when compared to peat soils previously exposed to saltwater conditions. Differences in soil surface deformation were also observed and related to differences in the soil matrix physical integrity across the salinity gradient. This work also uses electrical resistivity imaging surveys to image areas of peat collapse and demonstrates: (a) the role of salinity in the development of collapse features; and (b) the apparent lack of evidence to suggest subsurface lithological controls on the development of collapse features. A simplified conceptual framework for better understanding peat collapse and pock formation is presented.
Inhibition of miR338 rescues cleidocranial dysplasia in Runx2 mutant mice partially via the Hif1a-Vegfa axis
Authors: Jin Runze , Zhang Hanshu , Lin Chujiao , Guo Jinqiang , Zou Weiguo , Chen Zhi , Liu Huan 
Published: January 2023

AbstractHaploinsufficiency of Runt-related transcription factor-2 (RUNX2) is responsible for cleidocranial dysplasia (CCD), a rare hereditary disease with a range of defects, including delayed closure of the cranial sutures and short stature. Symptom-based treatments, such as a combined surgical-orthodontic approach, are commonly used to treat CCD patients. However, there have been few reports of treatments based on Runx2-specific regulation targeting dwarfism symptoms. Previously, we found that the miR338 cluster, a potential diagnostic and therapeutic target for postmenopausal osteoporosis, could directly target Runx2 during osteoblast differentiation in vitro. Here, we generated miR338−/−;Runx2+/− mice to investigate whether inhibition of miR338 could rescue CCD defects caused by Runx2 mutation in vivo. We found that the dwarfism phenotype caused by Runx2 haploinsufficiency was recovered in miR338−/−;Runx2+/− mice, with complete bone density restoration and quicker closure of fontanels. Single-cell RNA-seq analysis revealed that knockout of miR338 specifically rescued the osteoblast lineage priming ability of bone marrow stromal cells in Runx2+/− femurs, which was further confirmed by Osterix-specific conditional knockout of miR338 in Runx2+/− mice (OsxCre; miR338fl/fl;Runx2+/−). Mechanistically, ablation of the miR338 cluster in Runx2+/− femurs directly rescued the Hif1a-Vegfa pathway in Runx2+/− osteoblasts, as proven by gene expression profiles and ChIP and Re-ChIP assays. Collectively, our data revealed the genetic interaction between Runx2 and the miR338 cluster during osteoblast differentiation and implied that the miR338 cluster could be a potential therapeutic target for CCD.
Dynamic network biomarker identifies cdkn1a-mediated bone mineralization in the triggering phase of osteoporosis
Authors: Guo Weiming , Jin Peng , Li Ruomei , Huang Lu , Liu Zhen , Li Hairui , Zhou Ting , Fang Bing , Xia Lunguo 
Published: January 2023

AbstractThe identification of predictive markers to determine the triggering phase prior to the onset of osteoporosis is essential to mitigate further irrevocable deterioration. To determine the early warning signs before osteoporosis, we used the dynamic network biomarker (DNB) approach to analyze time-series gene expression data in a zebrafish osteoporosis model, which revealed that cyclin-dependent kinase inhibitor 1 A (cdkn1a) is a core DNB. We found that cdkn1a negatively regulates osteogenesis, as evidenced by loss-of-function and gain-of-function studies. Specifically, CRISPR/Cas9-mediated cdkn1a knockout in zebrafish significantly altered skeletal development and increased bone mineralization, whereas inducible cdkn1a expression significantly contributed to osteoclast differentiation. We also found several mechanistic clues that cdkn1a participates in osteoclast differentiation by regulating its upstream signaling cascades. To summarize, in this study, we provided new insights into the dynamic nature of osteoporosis and identified cdkn1a as an early-warning signal of osteoporosis onset.
A flexible pressure sensor with highly customizable sensitivity and linearity via positive design of microhierarchical structures with a hyperelastic model
Authors: Xu Zhenjin , Wu Dezhi , Chen Zhiwen , Wang Zhongbao , Cao Cong , Shao Xiangyu , Zhou Gang , Zhang Shaohua , Wang Lingyun , Sun Daoheng 
Published: January 2023

AbstractThe tactile pressure sensor is of great significance in flexible electronics, but sensitivity customization over the required working range with high linearity still remains a critical challenge. Despite numerous efforts to achieve high sensitivity and a wide working range, most sensitive microstructures tend to be obtained only by inverting naturally existing templates without rational design based on fundamental contact principles or models for piezoresistive pressure sensors. Here, a positive design strategy with a hyperelastic model and a Hertzian contact model for comparison was proposed to develop a flexible pressure sensor with highly customizable linear sensitivity and linearity, in which the microstructure distribution was precalculated according to the desired requirement prior to fabrication. As a proof of concept, three flexible pressure sensors exhibited sensitivities of 0.7, 1.0, and 1.3 kPa−1 over a linear region of up to 200 kPa, with a low sensitivity error (<5%) and high linearity (~0.99), as expected. Based on the superior electromechanical performance of these sensors, potential applications in physiological signal recognition are demonstrated as well, and such a strategy could shed more light on demand-oriented scenarios, including designable working ranges and linear sensitivity for next-generation wearable devices.
Implications and prognostic impact of mass spectrometry in patients with newly-diagnosed multiple myeloma
Authors: Mai Elias K. , Huhn Stefanie , Miah Kaya , Poos Alexandra M. , Scheid Christof , Weisel Katja C. , Bertsch Uta , Munder Markus , Berlanga Oscar , Hose Dirk , Seckinger Anja , Jauch Anna , Blau Igor W. , Hänel Mathias , Salwender Hans J. , Benner Axel , Raab Marc S. , Goldschmidt Hartmut , Weinhold Niels 
Published: January 2023

AbstractMass spectrometry (MS) is a promising tool for monitoring monoclonal protein in plasma cell dyscrasias. We included 480 transplant-eligible newly-diagnosed multiple myeloma (MM) patients from the GMMG-MM5 trial (EudraCT No. 2010-019173-16) and performed a retrospective MS analysis at baseline (480 patients) and at the pre-defined, consecutive time points after induction (444 patients), prior to maintenance (305 patients) and after one year of maintenance (227 patients). We found that MS negativity was significantly associated with improved progression-free survival (PFS) even in patients with complete response (CR) at all investigated follow-up time points. The prognostic impact was independent of established risk factors, such as the revised International Staging System. Combining MS and baseline cytogenetics improved the prediction of outcome: MS-positive patients with high-risk cytogenetics had a dismal PFS of 1.9 years (95% confidence interval [CI]: 1.6–2.3 years) from the start of maintenance. Testing the value of sequential MS prior to and after one year of maintenance, patients converting from MS positivity to negativity had an excellent PFS (median not reached) while patients converting from MS negativity to positivity progressed early (median 0.6 years, 95% CI: 0.3-not reached). Among patients with sustained MS positivity, the baseline high-risk cytogenetic status had a significant impact and defined a group with poor PFS. Combining minimal residual disease (MRD) in the bone marrow and MS allowed the identification of double negative patients with a favorable PFS (median 3.33 years, 95% CI: 3.08-not reached) and no overall survival events. Our study provides strong evidence that MS is superior to conventional response monitoring, highlighting the potential of MS to become a new standard. Our data indicate that MS should be performed sequentially and combined with baseline disease features and MRD to improve its clinical value.Clinical Trials Register: EudraCT No. 2010-019173-16
The Cancer Research UK Stratified Medicine Programme as a model for delivering personalised cancer care
Authors: Cerone Maria Antonietta , Mills Tara C. , Sharpe Rowena , McBride David , MacDonald Moira , MacMahon Suzanne , Mugalaasi Hood , Rehal Pauline , Rettino Alessandro , Roberts Helen , Ross Mark , White Donald Edward , Peden John , Rawlinson Janette , Ho Steffan N. , Hollingsworth Simon , Popat Sanjay , Middleton Gary , Johnson Peter , Swanton Charles ,   the SMP2 consortium, Man Somai , Butler Rachel , White Rhian , Morgan Sian , Wood Sian , Thompson Lisa , Carr Hedley , Subramaniam Sumi , McGuire Cian , Pitman Helen , Chen Isabella , Tunna Kirsty , Rehman Sahar , Middleton Catrin , Alvi Abdullah 
Published: January 2023

SummaryGenomic screening is routinely used to guide the treatment of cancer patients in many countries. However, several multi-layered factors make this effort difficult to deliver within a clinically relevant timeframe. Here we share the learnings from the CRUK-funded Stratified Medicine Programme for advanced NSCLC patients, which could be useful to better plan future studies.
Spontaneous vortex formation by microswimmers with retarded attractions
Authors: Wang Xiangzun , Chen Pin-Chuan , Kroy Klaus , Holubec Viktor , Cichos Frank 
Published: January 2023

AbstractCollective states of inanimate particles self-assemble through physical interactions and thermal motion. Despite some phenomenological resemblance, including signatures of criticality, the autonomous dynamics that binds motile agents into flocks, herds, or swarms allows for much richer behavior. Low-dimensional models have hinted at the crucial role played in this respect by perceived information, decision-making, and feedback, implying that the corresponding interactions are inevitably retarded. Here we present experiments on spherical Brownian microswimmers with delayed self-propulsion toward a spatially fixed target. We observe a spontaneous symmetry breaking to a transiently chiral dynamical state and concomitant critical behavior that do not rely on many-particle cooperativity. By comparison with the stochastic delay differential equation of motion of a single swimmer, we pinpoint the delay-induced effective synchronization of the swimmers with their own past as the key mechanism. Increasing numbers of swimmers self-organize into layers with pro- and retrograde orbital motion, synchronized and stabilized by steric, phoretic, and hydrodynamic interactions. Our results demonstrate how even most simple retarded interactions can foster emergent complex adaptive behavior in small active-particle ensembles.
Terahertz waveform synthesis in integrated thin-film lithium niobate platform
Authors: Herter Alexa , Shams-Ansari Amirhassan , Settembrini Francesca Fabiana , Warner Hana K. , Faist Jérôme , Lončar Marko , Benea-Chelmus Ileana-Cristina 
Published: January 2023

AbstractBridging the “terahertz gap“ relies upon synthesizing arbitrary waveforms in the terahertz domain enabling applications that require both narrow band sources for sensing and few-cycle drives for classical and quantum objects. However, realization of custom-tailored waveforms needed for these applications is currently hindered due to limited flexibility for optical rectification of femtosecond pulses in bulk crystals. Here, we experimentally demonstrate that thin-film lithium niobate circuits provide a versatile solution for such waveform synthesis by combining the merits of complex integrated architectures, low-loss distribution of pump pulses on-chip, and an efficient optical rectification. Our distributed pulse phase-matching scheme grants shaping the temporal, spectral, phase, amplitude, and farfield characteristics of the emitted terahertz field through designer on-chip components. This strictly circumvents prior limitations caused by the phase-delay mismatch in conventional systems and relaxes the requirement for cumbersome spectral pre-engineering of the pumping light. We propose a toolbox of basic blocks that produce broadband emission up to 680 GHz and far-field amplitudes of a few V m−1 with adaptable phase and coherence properties by using near-infrared pump pulse energies below 100 pJ.
PQBP5/NOL10 maintains and anchors the nucleolus under physiological and osmotic stress conditions
Authors: Jin Xiaocen , Tanaka Hikari , Jin Meihua , Fujita Kyota , Homma Hidenori , Inotsume Maiko , Yong Huang , Umeda Kenichi , Kodera Noriyuki , Ando Toshio , Okazawa Hitoshi 
Published: January 2023

AbstractPolyglutamine binding protein 5 (PQBP5), also called nucleolar protein 10 (NOL10), binds to polyglutamine tract sequences and is expressed in the nucleolus. Using dynamic imaging of high-speed atomic force microscopy, we show that PQBP5/NOL10 is an intrinsically disordered protein. Super-resolution microscopy and correlative light and electron microscopy method show that PQBP5/NOL10 makes up the skeletal structure of the nucleolus, constituting the granule meshwork in the granular component area, which is distinct from other nucleolar substructures, such as the fibrillar center and dense fibrillar component. In contrast to other nucleolar proteins, which disperse to the nucleoplasm under osmotic stress conditions, PQBP5/NOL10 remains in the nucleolus and functions as an anchor for reassembly of other nucleolar proteins. Droplet and thermal shift assays show that the biophysical features of PQBP5/NOL10 remain stable under stress conditions, explaining the spatial role of this protein. PQBP5/NOL10 can be functionally depleted by sequestration with polyglutamine disease proteins in vitro and in vivo, leading to the pathological deformity or disappearance of the nucleolus. Taken together, these findings indicate that PQBP5/NOL10 is an essential protein needed to maintain the structure of the nucleolus.
Ligand-controlled stereodivergent alkenylation of alkynes to access functionalized trans- and cis-1,3-dienes
Authors: Long Tianyu , Zhu Chen , Li Ling , Shao Liang , Zhu Shengqing , Rueping Magnus , Chu Lingling 
Published: January 2023

AbstractPrecise stereocontrol of functionalized alkenes represents a long-standing research topic in organic synthesis. Nevertheless, the development of a catalytic, easily tunable synthetic approach for the stereodivergent synthesis of bothE-selective and even more challengingZ-selective highly substituted 1,3-dienes from common substrates remains underexploited. Here, we report a photoredox and nickel dual catalytic strategy for the stereodivergent sulfonylalkenylation of terminal alkynes with vinyl triflates and sodium sulfinates under mild conditions. With a judicious choice of simple nickel catalyst and ligand, this method enables efficient and divergent access to bothZ-andE-sulfonyl-1,3-dienes from the same set of simple starting materials. This method features broad substrate scope, good functional compatibility, and excellent chemo-, regio-, and stereoselectivity. Experimental and DFT mechanistic studies offer insights into the observed divergent stereoselectivity controlled by ligands.
Unique ligand and kinase-independent roles of the insulin receptor in regulation of cell cycle, senescence and apoptosis
Authors: Nagao Hirofumi , Jayavelu Ashok Kumar , Cai Weikang , Pan Hui , Dreyfuss Jonathan M. , Batista Thiago M. , Brandão Bruna B. , Mann Matthias , Kahn C. Ronald 
Published: January 2023

AbstractInsulin acts through the insulin receptor (IR) tyrosine kinase to exert its classical metabolic and mitogenic actions. Here, using receptors with either short or long deletion of the β-subunit or mutation of the kinase active site (K1030R), we have uncovered a second, previously unrecognized IR signaling pathway that is intracellular domain-dependent, but ligand and tyrosine kinase-independent (LYK-I). These LYK-I actions of the IR are linked to changes in phosphorylation of a network of proteins involved in the regulation of extracellular matrix organization, cell cycle, ATM signaling and cellular senescence; and result in upregulation of expression of multiple extracellular matrix-related genes and proteins, down-regulation of immune/interferon-related genes and proteins, and increased sensitivity to apoptosis. Thus, in addition to classical ligand and tyrosine kinase-dependent (LYK-D) signaling, the IR regulates a second, ligand and tyrosine kinase-independent (LYK-I) pathway, which regulates the cellular machinery involved in senescence, matrix interaction and response to extrinsic challenges.
Rapid, label-free histopathological diagnosis of liver cancer based on Raman spectroscopy and deep learning
Authors: Huang Liping , Sun Hongwei , Sun Liangbin , Shi Keqing , Chen Yuzhe , Ren Xueqian , Ge Yuancai , Jiang Danfeng , Liu Xiaohu , Knoll Wolfgang , Zhang Qingwen , Wang Yi 
Published: January 2023

AbstractBiopsy is the recommended standard for pathological diagnosis of liver carcinoma. However, this method usually requires sectioning and staining, and well-trained pathologists to interpret tissue images. Here, we utilize Raman spectroscopy to study human hepatic tissue samples, developing and validating a workflow for in vitro and intraoperative pathological diagnosis of liver cancer. We distinguish carcinoma tissues from adjacent non-tumour tissues in a rapid, non-disruptive, and label-free manner by using Raman spectroscopy combined with deep learning, which is validated by tissue metabolomics. This technique allows for detailed pathological identification of the cancer tissues, including subtype, differentiation grade, and tumour stage. 2D/3D Raman images of unprocessed human tissue slices with submicrometric resolution are also acquired based on visualization of molecular composition, which could assist in tumour boundary recognition and clinicopathologic diagnosis. Lastly, the potential for a portable handheld Raman system is illustrated during surgery for real-time intraoperative human liver cancer diagnosis.
Surface passivation of intensely luminescent all-inorganic nanocrystals and their direct optical patterning
Authors: Xiao Pengwei , Zhang Zhoufan , Ge Junjun , Deng Yalei , Chen Xufeng , Zhang Jian-Rong , Deng Zhengtao , Kambe Yu , Talapin Dmitri V. , Wang Yuanyuan 
Published: January 2023

AbstractAll-inorganic nanocrystals (NCs) are of great importance in a range of electronic devices. However, current all-inorganic NCs suffer from limitations in their optical properties, such as low fluorescence efficiencies. Here, we develop a general surface treatment strategy to obtain intensely luminescent all-inorganic NCs (ILANs) by using designed metal salts with noncoordinating anions that play a dual role in the surface treatment process: (i) removing the original organic ligands and (ii) binding to unpassivated Lewis basic sites to preserve the photoluminescent (PL) properties of the NCs. The absolute photoluminescence quantum yields (PLQYs) of red-emitting CdSe/ZnS NCs, green-emitting CdSe/CdZnSeS/ZnS NCs and blue-emitting CdZnS/ZnS NCs in polar solvents are 97%, 80% and 72%, respectively. Further study reveals that the passivated Lewis basic sites of ILANs by metal cations boost the efficiency of radiative recombination of electron-hole pairs. While the passivation of Lewis basic sites leads to a high PLQY of ILANs, the exposed Lewis acidic sites provide the possibility for in situ tuning of the functions of NCs, creating opportunities for direct optical patterning of functional NCs with high resolution.