bluuebunny/crossref_metadata_2025_split huggingface dataset:
Economic costs at age five associated with very preterm birth: multinational European cohort study
Authors: Kim Sung Wook , Andronis Lazaros , Seppänen Anna-Veera , Aubert Adrien M. , Zeitlin Jennifer , Barros Henrique , Draper Elizabeth S. , Petrou Stavros ,   on behalf of the SHIPS Research Group,   Belgium, Lebeer J. , Van Reempts P. , Bruneel E. , Cloet E. , Oostra A. , Ortibus E. , Sarrechia I. ,   Denmark, Boerch K. , Pedersen P. ,   Estonia, Toome L. , Varendi H. , Männamaa M. ,   France, Ancel P. Y. , Burguet A. , Jarreau P. H. , Pierrat V. , Truffert P. ,   Germany, Maier R. F. , Zemlin M. , Misselwitz B. , Wohlers L. ,   Italy, Cuttini M. , Croci I. , Carnielli V. , Ancora G. , Faldella G. , Ferrari F. ,   The Netherlands, van Heijst A. , Koopman-Esseboom C. ,   Poland, Gadzinowski J. , Mazela J. , Montgomery A. , Pikuła T. ,   Portugal, Barros H. , Costa R. , Rodrigues C. ,   Sweden, Aden U. ,   United Kingdom, Draper E. S. , Fenton A. , Johnson S. J. ,   EFCNI, Mader S. , Thiele N. , Pfeil J. M. ,   Health Economics Team, Petrou S. , Kim S. W. , Andronis L. ,   Inserm Coordination, Zeitlin J. , Bonnet C. , El Rafei R. , Seppänen A. V. , Aubert A. M. 
Published: November 2021

Abstract
Background
This study aims to estimate the economic costs of care provided to children born very preterm and extremely preterm across 11 European countries, and to understand what perinatal and socioeconomic factors contribute to higher costs.

Methods
Generalised linear modelling was used to explore the association between perinatal and sociodemographic characteristics and total economic costs (€, 2016 prices) during the fifth year of life.

Results
Lower gestational age was associated with increased mean societal costs of €2755 (p < 0.001), €752 (p < 0.01) and €657 (p < 0.01) for children born at < 26, 26–27 and 28–29 weeks, respectively, in comparison to the reference group born at 30–31 weeks. A sensitivity analyses that excluded variables (BPD, any neonatal morbidity and presence of congenital anomaly) plausibly lying on the causal pathway between gestational age at birth and economic outcomes elevated incremental societal costs by €1482, €763 and €144 at < 26, 26–27 and 28–29 weeks, respectively, in comparison to the baseline model.

Conclusion
This study provides new evidence about the main cost drivers associated with preterm birth in European countries. Evidence identified by this study can act as inputs within cost-effectiveness models for preventive or treatment interventions for preterm birth.

Impact

What is the key message of your article? This study provides new evidence about the magnitude and drivers of economic costs associated with preterm birth in European countries.

What does it add to the existing literature? Lower gestational age is associated with increased mean societal costs during mid-childhood with indirect costs representing a key driver of increased costs.

What is the impact? For policy makers, this study adds to sparse evidence about the main cost drivers associated with preterm birth in European countries beyond the first 2 years of life.
Extent of myosin penetration within the actin cortex regulates cell surface mechanics
Authors: Truong Quang Binh An , Peters Ruby , Cassani Davide A. D. , Chugh Priyamvada , Clark Andrew G. , Agnew Meghan , Charras Guillaume , Paluch Ewa K. 
Published: November 2021

AbstractIn animal cells, shape is mostly determined by the actomyosin cortex, a thin cytoskeletal network underlying the plasma membrane. Myosin motors generate tension in the cortex, and tension gradients result in cellular deformations. As such, many cell morphogenesis studies have focused on the mechanisms controlling myosin activity and recruitment to the cortex. Here, we demonstrate using super-resolution microscopy that myosin does not always overlap with actin at the cortex, but remains restricted towards the cytoplasm in cells with low cortex tension. We propose that this restricted penetration results from steric hindrance, as myosin minifilaments are considerably larger than the cortical actin meshsize. We identify myosin activity and actin network architecture as key regulators of myosin penetration into the cortex, and show that increasing myosin penetration increases cortical tension. Our study reveals that the spatial coordination of myosin and actin at the cortex regulates cell surface mechanics, and unveils an important mechanism whereby myosin size controls its action by limiting minifilament penetration into the cortical actin network. More generally, our findings suggest that protein size could regulate function in dense cytoskeletal structures.
Low-latency time-of-flight non-line-of-sight imaging at 5 frames per second
Authors: Nam Ji Hyun , Brandt Eric , Bauer Sebastian , Liu Xiaochun , Renna Marco , Tosi Alberto , Sifakis Eftychios , Velten Andreas 
Published: November 2021

AbstractNon-Line-Of-Sight (NLOS) imaging aims at recovering the 3D geometry of objects that are hidden from the direct line of sight. One major challenge with this technique is the weak available multibounce signal limiting scene size, capture speed, and reconstruction quality. To overcome this obstacle, we introduce a multipixel time-of-flight non-line-of-sight imaging method combining specifically designed Single Photon Avalanche Diode (SPAD) array detectors with a fast reconstruction algorithm that captures and reconstructs live low-latency videos of non-line-of-sight scenes with natural non-retroreflective objects. We develop a model of the signal-to-noise-ratio of non-line-of-sight imaging and use it to devise a method that reconstructs the scene such that signal-to-noise-ratio, motion blur, angular resolution, and depth resolution are all independent of scene depth suggesting that reconstruction of very large scenes may be possible.
Targeting chondrocytes for arresting bony fusion in ankylosing spondylitis
Authors: Shao Fenli , Liu Qianqian , Zhu Yuyu , Fan Zhidan , Chen Wenjun , Liu Shijia , Li Xiaohui , Guo Wenjie , Feng Gen-Sheng , Yu Haiguo , Xu Qiang , Sun Yang 
Published: November 2021

Abstract
Bony fusion caused by pathological new bone formation manifests the clinical feature of ankylosing spondylitis (AS). However, the underlying mechanism remains elusive. Here we discovered spontaneous kyphosis, arthritis and bony fusion in mature CD4-Cre;Ptpn11
f/f mice, which present the pathophysiological features of AS. A population of CD4-Cre-expressing proliferating chondrocytes was SHP2 deficient, which could differentiate into pre-hypertrophic and hypertrophic chondrocytes. Functionally, SHP2 deficiency in chondrocytes impeded the fusion of epiphyseal plate and promoted chondrogenesis in joint cavity and enthesis. Mechanistically, aberrant chondrocytes promoted ectopic new bone formation through BMP6/pSmad1/5 signaling. It is worth emphasizing that such pathological thickness of growth plates was evident in adolescent humans with enthesitis-related arthritis, which could progress to AS in adulthood. Targeting dysfunctional chondrogenesis with Smo inhibitor sonidegib significantly alleviated the AS-like bone disease in mice. These findings suggest that blockade of chondrogenesis by sonidegib would be a drug repurposing strategy for AS treatment.
The parent-of-origin lncRNA MISSEN regulates rice endosperm development
Authors: Zhou Yan-Fei , Zhang Yu-Chan , Sun Yu-Meng , Yu Yang , Lei Meng-Qi , Yang Yu-Wei , Lian Jian-Ping , Feng Yan-Zhao , Zhang Zhi , Yang Lu , He Rui-Rui , Huang Jia-Hui , Cheng Yu , Liu Yu-Wei , Chen Yue-Qin 
Published: November 2021

AbstractThe cereal endosperm is a major factor determining seed size and shape. However, the molecular mechanisms of endosperm development are not fully understood. Long noncoding RNAs (lncRNAs) function in various biological processes. Here we show a lncRNA, MISSEN, that plays an essential role in early endosperm development in rice (Oryza sativa). MISSEN is a parent-of-origin lncRNA expressed in endosperm, and negatively regulates endosperm development, leading to a prominent dent and bulge in the seed. Mechanistically, MISSEN functions through hijacking a helicase family protein (HeFP) to regulate tubulin function during endosperm nucleus division and endosperm cellularization, resulting in abnormal cytoskeletal polymerization. Finally, we revealed that the expression of MISSEN is inhibited by histone H3 lysine 27 trimethylation (H3K27me3) modification after pollination. Therefore, MISSEN is the first lncRNA identified as a regulator in endosperm development, highlighting the potential applications in rice breeding.
Cryo-EM structure provides insights into the dimer arrangement of the O-linked β-N-acetylglucosamine transferase OGT
Authors: Meek Richard W. , Blaza James N. , Busmann Jil A. , Alteen Matthew G. , Vocadlo David J. , Davies Gideon J. 
Published: November 2021

AbstractThe O-linked β-N-acetylglucosamine modification is a core signalling mechanism, with erroneous patterns leading to cancer and neurodegeneration. Although thousands of proteins are subject to this modification, only a single essential glycosyltransferase catalyses its installation, the O-GlcNAc transferase, OGT. Previous studies have provided truncated structures of OGT through X-ray crystallography, but the full-length protein has never been observed. Here, we report a 5.3 Å cryo-EM model of OGT. We show OGT is a dimer, providing a structural basis for how some X-linked intellectual disability mutations at the interface may contribute to disease. We observe that the catalytic section of OGT abuts a 13.5 tetratricopeptide repeat unit region and find the relative positioning of these sections deviate from the previously proposed, X-ray crystallography-based model. We also note that OGT exhibits considerable heterogeneity in tetratricopeptide repeat units N-terminal to the dimer interface with repercussions for how OGT binds protein ligands and partners.
A modular toolbox to generate complex polymeric ubiquitin architectures using orthogonal sortase enzymes
Authors: Fottner Maximilian , Weyh Maria , Gaussmann Stefan , Schwarz Dominic , Sattler Michael , Lang Kathrin 
Published: November 2021

AbstractThe post-translational modification of proteins with ubiquitin (Ub) and Ub-like modifiers (Ubls) represents one of the most important regulators in eukaryotic biology. Polymeric Ub/Ubl chains of distinct topologies control the activity, stability, interaction and localization of almost all cellular proteins and elicit a variety of biological outputs. Our ability to characterize the roles of distinct Ub/Ubl topologies and to identify enzymes and receptors that create, recognize and remove these modifications is however hampered by the difficulty to prepare them. Here we introduce a modular toolbox (Ubl-tools) that allows the stepwise assembly of Ub/Ubl chains in a flexible and user-defined manner facilitated by orthogonal sortase enzymes. We demonstrate the universality and applicability of Ubl-tools by generating distinctly linked Ub/Ubl hybrid chains, and investigate their role in DNA damage repair. Importantly, Ubl-tools guarantees straightforward access to target proteins, site-specifically modified with distinct homo- and heterotypic (including branched) Ub chains, providing a powerful approach for studying the functional impact of these complex modifications on cellular processes.
Nitrate restricts nodule organogenesis through inhibition of cytokinin biosynthesis in Lotus japonicus
Authors: Lin Jieshun , Roswanjaya Yuda Purwana , Kohlen Wouter , Stougaard Jens , Reid Dugald 
Published: November 2021

AbstractLegumes balance nitrogen acquisition from soil nitrate with symbiotic nitrogen fixation. Nitrogen fixation requires establishment of a new organ, which is a cytokinin dependent developmental process in the root. We found cytokinin biosynthesis is a central integrator, balancing nitrate signalling with symbiotic acquired nitrogen. Low nitrate conditions provide a permissive state for induction of cytokinin by symbiotic signalling and thus nodule development. In contrast, high nitrate is inhibitory to cytokinin accumulation and nodule establishment in the root zone susceptible to nodule formation. This reduction of symbiotic cytokinin accumulation was further exacerbated in cytokinin biosynthesis mutants, which display hypersensitivity to nitrate inhibition of nodule development, maturation and nitrogen fixation. Consistent with this, cytokinin application rescues nodulation and nitrogen fixation of biosynthesis mutants in a concentration dependent manner. These inhibitory impacts of nitrate on symbiosis occur in a Nlp1 and Nlp4 dependent manner and contrast with the positive influence of nitrate on cytokinin biosynthesis that occurs in species that do not form symbiotic root nodules. Altogether this shows that legumes, as exemplified by Lotus japonicus, have evolved a different cytokinin response to nitrate compared to non-legumes.
Interferon-driven brain phenotype in a mouse model of RNaseT2 deficient leukoencephalopathy
Authors: Kettwig Matthias , Ternka Katharina , Wendland Kristin , Krüger Dennis Manfred , Zampar Silvia , Schob Charlotte , Franz Jonas , Aich Abhishek , Winkler Anne , Sakib M. Sadman , Kaurani Lalit , Epple Robert , Werner Hauke B. , Hakroush Samy , Kitz Julia , Prinz Marco , Bartok Eva , Hartmann Gunther , Schröder Simone , Rehling Peter , Henneke Marco , Boretius Susann , Alia A. , Wirths Oliver , Fischer Andre , Stadelmann Christine , Nessler Stefan , Gärtner Jutta 
Published: November 2021

AbstractInfantile-onset RNaseT2 deficient leukoencephalopathy is characterised by cystic brain lesions, multifocal white matter alterations, cerebral atrophy, and severe psychomotor impairment. The phenotype is similar to congenital cytomegalovirus brain infection and overlaps with type I interferonopathies, suggesting a role for innate immunity in its pathophysiology. To date, pathophysiological studies have been hindered by the lack of mouse models recapitulating the neuroinflammatory encephalopathy found in patients. In this study, we generated Rnaset2−/− mice using CRISPR/Cas9-mediated genome editing. Rnaset2−/− mice demonstrate upregulation of interferon-stimulated genes and concurrent IFNAR1-dependent neuroinflammation, with infiltration of CD8+ effector memory T cells and inflammatory monocytes into the grey and white matter. Single nuclei RNA sequencing reveals homeostatic dysfunctions in glial cells and neurons and provide important insights into the mechanisms of hippocampal-accentuated brain atrophy and cognitive impairment. The Rnaset2−/− mice may allow the study of CNS damage associated with RNaseT2 deficiency and may be used for the investigation of potential therapies.
Applying laboratory methods for durability assessment of vitrified material to archaeological samples
Authors: Nava-Farias Lorena , Neeway James J. , Schweiger Michael J. , Marcial José , Canfield Nathan L. , Pearce Carolyn I. , Peeler David K. , Vicenzi Edward P. , Kosson David S. , Delapp Rossane C. , McCloy John S. , Walling Sam A. , Thorpe Clare L. , Corkhill Claire L. , Hand Russell J. , Sjöblom Rolf , Kruger Albert A. 
Published: November 2021

AbstractLaboratory testing used to assess the long-term chemical durability of nuclear waste forms may not be applicable to disposal because the accelerated conditions may not represent disposal conditions. To address this, we examine the corrosion of vitrified archeological materials excavated from the near surface of a ~1500-year old Iron Age Swedish hillfort, Broborg, as an analog for the disposal of vitrified nuclear waste. We compare characterized site samples with corrosion characteristics generated by standard laboratory durability test methods including the product consistency test (PCT), the vapor hydration test (VHT), and the EPA Method 1313 test. Results show that the surficial layer of the Broborg samples resulting from VHT displays some similarities to the morphology of the surficial layer formed over longer timescales in the environment. This work provides improved understanding of long-term glass corrosion behavior in terms of the thickness, morphology, and chemistry of the surficial features that are formed.
Interleaved practice enhances memory and problem-solving ability in undergraduate physics
Authors: Samani Joshua , Pan Steven C. 
Published: November 2021

AbstractWe investigated whether continuously alternating between topics during practice, or interleaved practice, improves memory and the ability to solve problems in undergraduate physics. Over 8 weeks, students in two lecture sections of a university-level introductory physics course completed thrice-weekly homework assignments, each containing problems that were interleaved (i.e., alternating topics) or conventionally arranged (i.e., one topic practiced at a time). On two surprise criterial tests containing novel and more challenging problems, students recalled more relevant information and more frequently produced correct solutions after having engaged in interleaved practice (with observed median improvements of 50% on test 1 and 125% on test 2). Despite benefiting more from interleaved practice, students tended to rate the technique as more difficult and incorrectly believed that they learned less from it. Thus, in a domain that entails considerable amounts of problem-solving, replacing conventionally arranged with interleaved homework can (despite perceptions to the contrary) foster longer lasting and more generalizable learning.
Regulating role of abscisic acid on cadmium enrichment in ramie (Boehmeria nivea L.)
Authors: Chen Kunmei , Chen Ping , Qiu Xiaojun , Chen Jikang , Gao Gang , Wang Xiaofei , Zhu Aiguo , Yu Chunming 
Published: November 2021

AbstractAbscisic acid (ABA) is known as an important hormone regulating plant stress resistance, such as salt, drought and heavy metal resistance. However, the relationship between ABA and cadmium (Cd) enrichment in ramie (Boehmeria nivea L.) is still unclear to date. This study aimed to reveal the effect of ABA on Cd enrichment in ramie, and we received the following results: (1) Under Cd treatment, the Cd uptake of ramie increased with the increase of Cd concentration, but the chlorophyll content decreased. Under Cd treatment, the ABA content was highest in roots of ramie, followed by that in old leaves, and lowest in new leaves. Long-time treatment of high Cd concentration reduced the ability of endogenous ABA biosynthesis. (2) Spraying ABA on ramie plants (SORP) and adding ABA directly to the culture solution (ADCS) with low concentration can promote the growth of ramie and increase the amount of Cd uptake, and the effect of SORP is better. (3) The molecular reason for the decrease of chlorophyll content due to Cd stress, may be resulted from the down-regulated expression of the chlorophyll synthesis genes (BnPAO and BnNYC1) and the up-regulated expression of the chlorophyll degradation genes (BnCHLH, BnCHLG, BnHAP3A and BnPPR1). The elevated ABA content in ramie plants may due to the up-regulated expression of the ABA synthesis related genes (BnABA1, BnNCED3, and BnNCED5) and the genes (BnABCG40, BnNFXL2, BnPYL9, BnGCR2, BnGTG1, BnBGLU1, BnUTG1, BnVHAG1 and BnABI5) that encoding ABA transport and response proteins, which was consistent with the enhance the Cd uptake in ramie. Our study revealed the relationship between ABA and Cd uptake in ramie, which provided a reference for improving the enrichment of Cd in ramie.
Optimization of an ammonia assay based on transmembrane pH-gradient polymersomes
Authors: Spyrogianni Anastasia , Gourmel Charlotte , Hofmann Leopold , Marbach Jessica , Leroux Jean-Christophe 
Published: November 2021

AbstractReliable ammonia quantification assays are essential for monitoring ammonemia in patients with liver diseases. In this study, we describe the development process of a microplate-based assay for accurate, precise, and robust ammonia quantification in biological fluids, following regulatory guidelines on bioanalytical method validation. The assay is based on transmembrane pH-gradient polymersomes that encapsulate a pH-sensitive ratiometric fluorophore, the fluorescence signal of which correlates with the ammonia concentration in the sample. Using a four-parameter logistic regression, the assay had a large quantification range (30–800 μM ammonia). As for selectivity, the presence of amino acids or pyruvate (up to clinically relevant concentrations) showed no assay interference. In samples with low bilirubin levels, polymersomes containing the fluorophore pyranine provided accurate ammonia quantification. In samples with high bilirubin concentrations, billirubin’s optical interference was alleviated when replacing pyranine with a close to near-infrared hemicyanine fluorophore. Finally, the assay could correctly retrieve the ammonia concentration in ammonia-spiked human plasma samples, which was confirmed by comparing our measurements with the data obtained using a commercially available point-of-care device for ammonia.
Emergence of B.1.524(G) SARS-CoV-2 in Malaysia during the third COVID-19 epidemic wave
Authors: Tan Kim-Kee , Tan Jia-Yi , Wong Jo-Ern , Teoh Boon-Teong , Tiong Vunjia , Abd-Jamil Juraina , Nor’e Siti-Sarah , Khor Chee-Sieng , Johari Jefree , Yaacob Che-Norainon , Zulkifli Mulya-Mustika-Sari , CheMatSeri AsmaAnati , Mahfodz Nur-Hidayana , Azizan Noor Syahida , AbuBakar Sazaly 
Published: November 2021

AbstractThe COVID-19 pandemic first emerged in Malaysia in Jan 2020. As of 12th Sept 2021, 1,979,698 COVID-19 cases that occurred over three major epidemic waves were confirmed. The virus contributing to the three epidemic waves has not been well-studied. We sequenced the genome of 22 SARS-CoV-2 strains detected in Malaysia during the second and the ongoing third wave of the COVID-19 epidemic. Detailed phylogenetic and genetic variation analyses of the SARS-CoV-2 isolate genomes were performed using these newly determined sequences and all other available sequences. Results from the analyses suggested multiple independent introductions of SARS-CoV-2 into Malaysia. A new B.1.524(G) lineage with S-D614G mutation was detected in Sabah, East Malaysia and Selangor, Peninsular Malaysia on 7th October 2020 and 14th October 2020, respectively. This new B.1.524(G) group was not the direct descendant of any of the previously detected lineages. The new B.1.524(G) carried a set of genetic variations, including A701V (position variant frequency = 0.0007) in Spike protein and a novel G114T mutation at the 5’UTR. The biological importance of the specific mutations remained unknown. The sequential appearance of the mutations, however, suggests that the spread of the new B.1.524(G) lineages likely begun in Sabah and then spread to Selangor. The findings presented here support the importance of SARS-CoV-2 full genome sequencing as a tool to establish an epidemiological link between cases or clusters of COVID-19 worldwide.