bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genetic associations with carotid intima-media thickness link to atherosclerosis with sex-specific effects in sub-Saharan Africans
Authors: Boua Palwende Romuald , Brandenburg Jean-Tristan , Choudhury Ananyo , Sorgho Hermann , Nonterah Engelbert A. , Agongo Godfred , Asiki Gershim , Micklesfield Lisa , Choma Solomon , Gómez-Olivé Francesc Xavier , Hazelhurst Scott , Tinto Halidou , Crowther Nigel J. , Mathew Christopher G. , Ramsay Michèle ,   AWI-Gen Study,   the H3Africa Consortium
Published: February 2022

AbstractAtherosclerosis precedes the onset of clinical manifestations of cardiovascular diseases (CVDs). We used carotid intima-media thickness (cIMT) to investigate genetic susceptibility to atherosclerosis in 7894 unrelated adults (3963 women, 3931 men; 40 to 60 years) resident in four sub-Saharan African countries. cIMT was measured by ultrasound and genotyping was performed on the H3Africa SNP Array. Two new African-specific genome-wide significant loci for mean-max cIMT, SIRPA (p = 4.7E-08), and FBXL17 (p = 2.5E-08), were identified. Sex-stratified analysis revealed associations with one male-specific locus, SNX29 (p = 6.3E-09), and two female-specific loci, LARP6 (p = 2.4E-09) and PROK1 (p = 1.0E-08). We replicate previous cIMT associations with different lead SNPs in linkage disequilibrium with SNPs primarily identified in European populations. Our study find significant enrichment for genes involved in oestrogen response from female-specific signals. The genes identified show biological relevance to atherosclerosis and/or CVDs, sex-differences and transferability of signals from non-African studies.
Enantioselective Cu(I)-catalyzed borylative cyclization of enone-tethered cyclohexadienones and mechanistic insights
Authors: Jadhav Sandip B. , Dash Soumya Ranjan , Maurya Sundaram , Nanubolu Jagadeesh Babu , Vanka Kumar , Chegondi Rambabu 
Published: February 2022

AbstractThe catalytic asymmetric borylation of conjugated carbonyls followed by stereoselective intramolecular cascade cyclizations with in situ generated chiral enolates are extremely rare. Herein, we report the enantioselective Cu(I)-catalyzed β-borylation/Michael addition on prochiral enone-tethered 2,5-cyclohexadienones. This asymmetric desymmetrization strategy has a broad range of substrate scope to generate densely functionalized bicyclic enones bearing four contiguous stereocenters with excellent yield, enantioselectivity, and diastereoselectivity. One-pot borylation/cyclization/oxidation via the sequential addition of sodium perborate reagent affords the corresponding alcohols without affecting yield and enantioselectivity. The synthetic potential of this reaction is explored through gram-scale reactions and further chemoselective transformations on products. DFT calculations explain the requirement of the base in an equimolar ratio in the reaction, as it leads to the formation of a lithium-enolate complex to undergo C-C bond formation via a chair-like transition state, with a barrier that is 22.5 kcal/mol more favourable than that of the copper-enolate complex.
Mesenchymal stem cells transfer mitochondria to allogeneic Tregs in an HLA-dependent manner improving their immunosuppressive activity
Authors: Piekarska Karolina , Urban-Wójciuk Zuzanna , Kurkowiak Małgorzta , Pelikant-Małecka Iwona , Schumacher Adriana , Sakowska Justyna , Spodnik Jan Henryk , Arcimowicz Łukasz , Zielińska Hanna , Tymoniuk Bogusław , Renkielska Alicja , Siebert Janusz , Słomińska Ewa , Trzonkowski Piotr , Hupp Ted , Marek-Trzonkowska Natalia Maria 
Published: February 2022

AbstractCell-based immunotherapies can provide safe and effective treatments for various disorders including autoimmunity, cancer, and excessive proinflammatory events in sepsis or viral infections. However, to achieve this goal there is a need for deeper understanding of mechanisms of the intercellular interactions. Regulatory T cells (Tregs) are a lymphocyte subset that maintain peripheral tolerance, whilst mesenchymal stem cells (MSCs) are multipotent nonhematopoietic progenitor cells. Despite coming from different origins, Tregs and MSCs share immunoregulatory properties that have been tested in clinical trials. Here we demonstrate how direct and indirect contact with allogenic MSCs improves Tregs’ potential for accumulation of immunosuppressive adenosine and suppression of conventional T cell proliferation, making them more potent therapeutic tools. Our results also demonstrate that direct communication between Tregs and MSCs is based on transfer of active mitochondria and fragments of plasma membrane from MSCs to Tregs, an event that is HLA-dependent and associates with HLA-C and HLA-DRB1 eplet mismatch load between Treg and MSC donors.
A deep-learning system bridging molecule structure and biomedical text with comprehension comparable to human professionals
Authors: Zeng Zheni , Yao Yuan , Liu Zhiyuan , Sun Maosong 
Published: February 2022

AbstractTo accelerate biomedical research process, deep-learning systems are developed to automatically acquire knowledge about molecule entities by reading large-scale biomedical data. Inspired by humans that learn deep molecule knowledge from versatile reading on both molecule structure and biomedical text information, we propose a knowledgeable machine reading system that bridges both types of information in a unified deep-learning framework for comprehensive biomedical research assistance. We solve the problem that existing machine reading models can only process different types of data separately, and thus achieve a comprehensive and thorough understanding of molecule entities. By grasping meta-knowledge in an unsupervised fashion within and across different information sources, our system can facilitate various real-world biomedical applications, including molecular property prediction, biomedical relation extraction and so on. Experimental results show that our system even surpasses human professionals in the capability of molecular property comprehension, and also reveal its promising potential in facilitating automatic drug discovery and documentation in the future.
Structural insights into the Venus flytrap mechanosensitive ion channel Flycatcher1
Authors: Jojoa-Cruz Sebastian , Saotome Kei , Tsui Che Chun Alex , Lee Wen-Hsin , Sansom Mark S. P. , Murthy Swetha E. , Patapoutian Ardem , Ward Andrew B. 
Published: February 2022

AbstractFlycatcher1 (FLYC1), a MscS homolog, has recently been identified as a candidate mechanosensitive (MS) ion channel involved in Venus flytrap prey recognition. FLYC1 is a larger protein and its sequence diverges from previously studied MscS homologs, suggesting it has unique structural features that contribute to its function. Here, we characterize FLYC1 by cryo-electron microscopy, molecular dynamics simulations, and electrophysiology. Akin to bacterial MscS and plant MSL1 channels, we find that FLYC1 central core includes side portals in the cytoplasmic cage that regulate ion preference and conduction, by identifying critical residues that modulate channel conductance. Topologically unique cytoplasmic flanking regions can adopt ‘up’ or ‘down’ conformations, making the channel asymmetric. Disruption of an up conformation-specific interaction severely delays channel deactivation by 40-fold likely due to stabilization of the channel open state. Our results illustrate novel structural features and likely conformational transitions that regulate mechano-gating of FLYC1.
Dynamic FMR1 granule phase switch instructed by m6A modification contributes to maternal RNA decay
Authors: Zhang Guoqiang , Xu Yongru , Wang Xiaona , Zhu Yuanxiang , Wang Liangliang , Zhang Wenxin , Wang Yiru , Gao Yajie , Wu Xuna , Cheng Ying , Sun Qinmiao , Chen Dahua 
Published: February 2022

AbstractMaternal RNA degradation is critical for embryogenesis and is tightly controlled by maternal RNA-binding proteins. Fragile X mental-retardation protein (FMR1) binds target mRNAs to form ribonucleoprotein (RNP) complexes/granules that control various biological processes, including early embryogenesis. However, how FMR1 recognizes target mRNAs and how FMR1-RNP granule assembly/disassembly regulates FMR1-associated mRNAs remain elusive. Here we show that Drosophila FMR1 preferentially binds mRNAs containing m6A-marked “AGACU” motif with high affinity to contributes to maternal RNA degradation. The high-affinity binding largely depends on a hydrophobic network within FMR1 KH2 domain. Importantly, this binding greatly induces FMR1 granule condensation to efficiently recruit unmodified mRNAs. The degradation of maternal mRNAs then causes granule de-condensation, allowing normal embryogenesis. Our findings reveal that sequence-specific mRNAs instruct FMR1-RNP granules to undergo a dynamic phase-switch, thus contributes to maternal mRNA decay. This mechanism may represent a general principle that regulated RNP-granules control RNA processing and normal development.
Toward scalable fabrication of electrochemical paper sensor without surface functionalization
Authors: Wang Cheng , Wu Rui , Ling Hao , Zhao Zhiling , Han Wenjia , Shi Xiaowen , Payne Gregory F. , Wang Xiaohui 
Published: February 2022

AbstractPaper-based electrochemical sensors provide the opportunity for low-cost, portable and environmentally friendly single-use chemical analysis and there are various reports of surface-functionalized paper electrodes. Here we report a composite paper electrode that is fabricated through designed papermaking using cellulose, carbon fibers (CF), and graphene oxide (GO). The composite paper has well-controlled structure, stable, and repeatable properties, and offers the electrocatalytic activities for sensitive and selective chemical detection. We demonstrate that this CF/GO/cellulose composite paper can be reduced electrochemically using relatively mild conditions and this GO reduction confers electrocatalytic properties to the composite paper. Finally, we demonstrate that this composite paper offers sensing performance (sensitivity and selectivity) comparable to, or better than, paper-based sensors prepared by small-batch surface-modification (e.g., printing) methods. We envision this coupling of industrialized papermaking technologies with interfacial engineering and electrochemical reduction can provide a platform for single-use and portable chemical detection for a wide range of applications.
Increase in Arctic coastal erosion and its sensitivity to warming in the twenty-first century
Authors: Nielsen David Marcolino , Pieper Patrick , Barkhordarian Armineh , Overduin Paul , Ilyina Tatiana , Brovkin Victor , Baehr Johanna , Dobrynin Mikhail 
Published: February 2022

AbstractArctic coastal erosion damages infrastructure, threatens coastal communities and releases organic carbon from permafrost. However, the magnitude, timing and sensitivity of coastal erosion increase to global warming remain unknown. Here we project the Arctic-mean erosion rate to increase and very likely exceed its historical range of variability before the end of the century in a wide range of emission scenarios. The sensitivity of erosion to warming roughly doubles, reaching 0.4–0.8 m yr−1 °C−1 and 2.3–4.2 TgC yr−1 °C−1 by the end of the century. We develop a simplified semi-empirical model to produce twenty-first-century pan-Arctic coastal erosion rate projections. Our results will inform policymakers on coastal conservation and socioeconomic planning, and organic carbon flux projections lay out the path for future work to investigate the impact of Arctic coastal erosion on the changing Arctic Ocean, its role as a global carbon sink, and the permafrost–carbon feedback.
The hypertriglyceridemic waist phenotype is associated with fatty liver and glycometabolic profiles in overweight and obese adults: a cross-sectional study
Authors: Zhou Meiling , Li Feifei , Tang Haokai , Wu Si , Meng Li , Dong Yanhui , Wang Fei , Quach Binh , Yang Yide , Ma Jun , Baker Julien Steven 
Published: February 2022

AbstractThe present study aimed to distinguish different hypertriglyceridemic waist phenotypes and relevant risks of developing fatty liver and abnormal glycometabolic profiles in overweight/obese adults. A total of 1221 Chinese adults with mean (standard deviation [SD]) age of 37 (9) years, 37.3% males and 62.7% females, body mass index (BMI) of 29.0 (4.0) kg/m2, triglyceride (TG) 2.04 (1.45) mmol/L, and waist circumference (WC) 95.8 (10.7) cm were included and classified into four phenotypes: normal TG & normal WC (N-N); normal TG & high WC (N-WC); high TG & normal WC (TG-N); high TG & high WC (TG-WC). Participants in TG-WC group had the highest BMI, WC, blood pressure (BP), insulin, Homeostatic Model Assessment of Insulin Resistance (HOMA-IR), glycosylated hemoglobin (HbA1c), low-density lipoprotein cholesterol (LDL), and fatty liver. Participants within N-WC group had a significantly higher risk of fatty liver (adjusted OR 3.50 [95% CI 2.05–5.97]), as well as TG-N (adjusted OR 2.59 [95% CI 1.61–4.16]) and TG-WC (adjusted OR 4.12 [95% CI 2.28–7.46]). The risk of elevated HOMA-IR was significantly higher in TG-N (adjusted OR 2.16 [95% CI 1.33–3.50]) and TG-WC (adjusted OR 2.04 [95% CI 1.22–3.40]). The risk of elevated HbA1c was significantly higher in the TG-WC (adjusted OR 2.79 [95% CI 1.47–5.31]). Hypertriglyceridemic waist phenotype can be a potential and cost-effective method to identify individuals with a high risk of fatty liver and glycometabolic disorders.
Targeted deletion of the RNA-binding protein Caprin1 leads to progressive hearing loss and impairs recovery from noise exposure in mice
Authors: Nolan Lisa S. , Chen Jing , Gonçalves Ana-Cláudia , Bullen Anwen , Towers Emily R. , Steel Karen P. , Dawson Sally J. , Gale Jonathan E. 
Published: February 2022

AbstractCell cycle associated protein 1 (Caprin1) is an RNA-binding protein that can regulate the cellular post-transcriptional response to stress. It is a component of both stress granules and neuronal RNA granules and is implicated in neurodegenerative disease, synaptic plasticity and long-term memory formation. Our previous work suggested that Caprin1 also plays a role in the response of the cochlea to stress. Here, targeted inner ear-deletion of Caprin1 in mice leads to an early onset, progressive hearing loss. Auditory brainstem responses from Caprin1-deficient mice show reduced thresholds, with a significant reduction in wave-I amplitudes compared to wildtype. Whilst hair cell structure and numbers were normal, the inner hair cell-spiral ganglion neuron (IHC-SGN) synapse revealed abnormally large post-synaptic GluA2 receptor puncta, a defect consistent with the observed wave-I reduction. Unlike wildtype mice, mild-noise-induced hearing threshold shifts in Caprin1-deficient mice did not recover. Oxidative stress triggered TIA-1/HuR-positive stress granule formation in ex-vivo cochlear explants from Caprin1-deficient mice, showing that stress granules could still be induced. Taken together, these findings suggest that Caprin1 plays a key role in maintenance of auditory function, where it regulates the normal status of the IHC-SGN synapse.
Stochastic dynamics of a few sodium atoms in presence of a cold potassium cloud
Authors: Bhatt Rohit Prasad , Kilinc Jan , Höcker Lilo , Jendrzejewski Fred 
Published: February 2022

AbstractSingle particle resolution is a requirement for numerous experimental protocols that emulate the dynamics of small systems in a bath. Here, we accurately resolve through atom counting the stochastic dynamics of a few sodium atoms in presence of a cold potassium cloud. This capability enables us to rule out the effect of inter-species interaction on sodium atom number dynamics, at very low atomic densities present in these experiments. We study the noise sources for sodium and potassium in a common framework. Thereby, we assign the detection limits to 4.3 atoms for potassium and 0.2 atoms (corresponding to 96% fidelity) for sodium. This opens possibilities for future experiments with a few atoms immersed in a quantum degenerate gas.
Bodily ownership of an independent supernumerary limb: an exploratory study
Authors: Umezawa Kohei , Suzuki Yuta , Ganesh Gowrishankar , Miyawaki Yoichi 
Published: February 2022

AbstractCan our brain perceive a sense of ownership towards an independent supernumerary limb; one that can be moved independently of any other limb and provides its own independent movement feedback? Following the rubber-hand illusion experiment, a plethora of studies have shown that the human representation of “self” is very plastic. But previous studies have almost exclusively investigated ownership towards “substitute” artificial limbs, which are controlled by the movements of a real limb and/or limbs from which non-visual sensory feedback is provided on an existing limb. Here, to investigate whether the human brain can own an independent artificial limb, we first developed a novel independent robotic “sixth finger.” We allowed participants to train using the finger and examined whether it induced changes in the body representation using behavioral as well as cognitive measures. Our results suggest that unlike a substitute artificial limb (like in the rubber hand experiment), it is more difficult for humans to perceive a sense of ownership towards an independent limb. However, ownership does seem possible, as we observed clear tendencies of changes in the body representation that correlated with the cognitive reports of the sense of ownership. Our results provide the first evidence to show that an independent supernumerary limb can be embodied by humans.
Optimization, purification and characterization of laccase from Ganoderma leucocontextum along with its phylogenetic relationship
Authors: Umar Aisha , Ahmed Shakil 
Published: February 2022

AbstractThe aim of this work to study an efficient laccase producing fungus Ganoderma leucocontextum, which was identified by ITS regions of DNA and phylogenetic tree was constructed. This study showed the laccase first-time from G. leucocontextum by using medium containing guaiacol. The growth cultural (pH, temperature, incubation days, rpm) and nutritional (carbon and nitrogen sources) conditions were optimized, which enhanced the enzyme production up to 4.5-folds. Laccase production increased 855 U/L at 40 °C. The pH 5.0 was suitable for laccase secretion (2517 U/L) on the 7th day of incubation at 100 rpm (698.3 U/L). Glucose and sucrose were good carbon source to enhance the laccase synthesis. The 10 g/L beef (4671 U/L) and yeast extract (5776 U/L) were the best nitrogen source for laccase secretion from G. leucocontextum. The laccase was purified from the 80% ammonium sulphate precipitations of protein identified by nucleotides sequence. The molecular weight (65.0 kDa) of purified laccase was identified through SDS and native PAGE entitled as Glacc110. The Glacc110 was characterized under different parameters. It retained > 90% of its activity for 16 min incubation at 60 °C in acidic medium (pH 4.0). This enzyme exerted its optimal activity at pH 3.0 and temperature 70 °C with guaiacol substrate. The catalytic parameters Km and Vmax was 1.658 (mM) and 2.452 (mM/min), respectively. The thermo stability of the laccase produced by submerged fermentation of G. leucocontextum has potential for industrial and biotechnology applications. The results remarked the G. leucocontextum is a good source for laccase production.
Development of a code-free machine learning model for the classification of cataract surgery phases
Authors: Touma Samir , Antaki Fares , Duval Renaud 
Published: February 2022

AbstractThis study assessed the performance of automated machine learning (AutoML) in classifying cataract surgery phases from surgical videos. Two ophthalmology trainees without coding experience designed a deep learning model in Google Cloud AutoML Video Classification for the classification of 10 different cataract surgery phases. We used two open-access publicly available datasets (total of 122 surgeries) for model training, validation and testing. External validation was performed on 10 surgeries issued from another dataset. The AutoML model demonstrated excellent discriminating performance, even outperforming bespoke deep learning models handcrafter by experts. The area under the precision-recall curve was 0.855. At the 0.5 confidence threshold cut-off, the overall performance metrics were as follows: sensitivity (81.0%), recall (77.1%), accuracy (96.0%) and F1 score (0.79). The per-segment metrics varied across the surgical phases: precision 66.7–100%, recall 46.2–100% and specificity 94.1–100%. Hydrodissection and phacoemulsification were the most accurately predicted phases (100 and 92.31% correct predictions, respectively). During external validation, the average precision was 54.2% (0.00–90.0%), the recall was 61.1% (0.00–100%) and specificity was 96.2% (91.0–99.0%). In conclusion, a code-free AutoML model can accurately classify cataract surgery phases from videos with an accuracy comparable or better than models developed by experts.
A proficient approach to forecast COVID-19 spread via optimized dynamic machine learning models
Authors: Alali Yasminah , Harrou Fouzi , Sun Ying 
Published: February 2022

AbstractThis study aims to develop an assumption-free data-driven model to accurately forecast COVID-19 spread. Towards this end, we firstly employed Bayesian optimization to tune the Gaussian process regression (GPR) hyperparameters to develop an efficient GPR-based model for forecasting the recovered and confirmed COVID-19 cases in two highly impacted countries, India and Brazil. However, machine learning models do not consider the time dependency in the COVID-19 data series. Here, dynamic information has been taken into account to alleviate this limitation by introducing lagged measurements in constructing the investigated machine learning models. Additionally, we assessed the contribution of the incorporated features to the COVID-19 prediction using the Random Forest algorithm. Results reveal that significant improvement can be obtained using the proposed dynamic machine learning models. In addition, the results highlighted the superior performance of the dynamic GPR compared to the other models (i.e., Support vector regression, Boosted trees, Bagged trees, Decision tree, Random Forest, and XGBoost) by achieving an averaged mean absolute percentage error of around 0.1%. Finally, we provided the confidence level of the predicted results based on the dynamic GPR model and showed that the predictions are within the 95% confidence interval. This study presents a promising shallow and simple approach for predicting COVID-19 spread.