bluuebunny/crossref_metadata_2025_split huggingface dataset:
Correcting for sparsity and interdependence in glycomics by accounting for glycan biosynthesis
Authors: Bao Bokan , Kellman Benjamin P. , Chiang Austin W. T. , Zhang Yujie , Sorrentino James T. , York Austin K. , Mohammad Mahmoud A. , Haymond Morey W. , Bode Lars , Lewis Nathan E. 
Published: August 2021

AbstractGlycans are fundamental cellular building blocks, involved in many organismal functions. Advances in glycomics are elucidating the essential roles of glycans. Still, it remains challenging to properly analyze large glycomics datasets, since the abundance of each glycan is dependent on many other glycans that share many intermediate biosynthetic steps. Furthermore, the overlap of measured glycans can be low across samples. We address these challenges with GlyCompare, a glycomic data analysis approach that accounts for shared biosynthetic steps for all measured glycans to correct for sparsity and non-independence in glycomics, which enables direct comparison of different glycoprofiles and increases statistical power. Using GlyCompare, we study diverse N-glycan profiles from glycoengineered erythropoietin. We obtain biologically meaningful clustering of mutant cell glycoprofiles and identify knockout-specific effects of fucosyltransferase mutants on tetra-antennary structures. We further analyze human milk oligosaccharide profiles and find mother’s fucosyltransferase-dependent secretor-status indirectly impact the sialylation. Finally, we apply our method on mucin-type O-glycans, gangliosides, and site-specific compositional glycosylation data to reveal tissues and disease-specific glycan presentations. Our substructure-oriented approach will enable researchers to take full advantage of the growing power and size of glycomics data.
ELMO1 signaling is a promoter of osteoclast function and bone loss
Authors: Arandjelovic Sanja , Perry Justin S. A. , Zhou Ming , Ceroi Adam , Smirnov Igor , Walk Scott F. , Shankman Laura S. , Cambré Isabelle , Onengut-Gumuscu Suna , Elewaut Dirk , Conrads Thomas P. , Ravichandran Kodi S. 
Published: August 2021

AbstractOsteoporosis affects millions worldwide and is often caused by osteoclast induced bone loss. Here, we identify the cytoplasmic protein ELMO1 as an important ‘signaling node’ in osteoclasts. We note that ELMO1 SNPs associate with bone abnormalities in humans, and that ELMO1 deletion in mice reduces bone loss in four in vivo models: osteoprotegerin deficiency, ovariectomy, and two types of inflammatory arthritis. Our transcriptomic analyses coupled with CRISPR/Cas9 genetic deletion identify Elmo1 associated regulators of osteoclast function, including cathepsin G and myeloperoxidase. Further, we define the ‘ELMO1 interactome’ in osteoclasts via proteomics and reveal proteins required for bone degradation. ELMO1 also contributes to osteoclast sealing zone on bone-like surfaces and distribution of osteoclast-specific proteases. Finally, a 3D structure-based ELMO1 inhibitory peptide reduces bone resorption in wild type osteoclasts. Collectively, we identify ELMO1 as a signaling hub that regulates osteoclast function and bone loss, with relevance to osteoporosis and arthritis.
Single-cell sequencing of immune cells from anticitrullinated peptide antibody positive and negative rheumatoid arthritis
Authors: Wu Xunyao , Liu Yi , Jin Shanzhao , Wang Min , Jiao Yuhao , Yang Bo , Lu Xin , Ji Xin , Fei Yunyun , Yang Huaxia , Zhao Lidan , Chen Hua , Zhang Yaran , Li Hao , Lipsky Peter E. , Tsokos George C. , Bai Fan , Zhang Xuan 
Published: August 2021

AbstractThe presence or absence of anti-citrullinated peptide antibodies (ACPA) and associated disparities in patients with rheumatoid arthritis (RA) implies disease heterogeneity with unknown diverse immunopathological mechanisms. Here we profile CD45+ hematopoietic cells from peripheral blood or synovial tissues from both ACPA+ and ACPA- RA patients by single-cell RNA sequencing and identify subsets of immune cells that contribute to the pathogenesis of RA subtypes. We find several synovial immune cell abnormalities, including up-regulation of CCL13, CCL18 and MMP3 in myeloid cell subsets of ACPA- RA compared with ACPA+ RA. Also evident is a lack of HLA-DRB5 expression and lower expression of cytotoxic and exhaustion related genes in the synovial tissues of patients with ACPA- RA. Furthermore, the HLA-DR15 haplotype (DRB1/DRB5) conveys an increased risk of developing active disease in ACPA+ RA in a large cohort of patients with treatment-naive RA. Immunohistochemical staining shows increased infiltration of CCL13 and CCL18-expressing immune cells in synovial tissues of ACPA- RA. Collectively, our data provide evidence of the differential involvement of cellular and molecular pathways involved in the pathogenesis of seropositive and seronegative RA subtypes and reveal the importance of precision therapy based on ACPA status.
Spatiotemporally-resolved mapping of RNA binding proteins via functional proximity labeling reveals a mitochondrial mRNA anchor promoting stress recovery
Authors: Qin Wei , Myers Samuel A. , Carey Dominique K. , Carr Steven A. , Ting Alice Y. 
Published: August 2021

AbstractProximity labeling (PL) with genetically-targeted promiscuous enzymes has emerged as a powerful tool for unbiased proteome discovery. By combining the spatiotemporal specificity of PL with methods for functional protein enrichment, we show that it is possible to map specific protein subclasses within distinct compartments of living cells. In particular, we develop a method to enrich subcompartment-specific RNA binding proteins (RBPs) by combining peroxidase-catalyzed PL with organic-aqueous phase separation of crosslinked protein-RNA complexes (“APEX-PS”). We use APEX-PS to generate datasets of nuclear, nucleolar, and outer mitochondrial membrane (OMM) RBPs, which can be mined for novel functions. For example, we find that the OMM RBP SYNJ2BP retains specific nuclear-encoded mitochondrial mRNAs at the OMM during translation stress, facilitating their local translation and import of protein products into the mitochondrion during stress recovery. Functional PL in general, and APEX-PS in particular, represent versatile approaches for the discovery of proteins with novel function in specific subcellular compartments.
In situ ultrastructures of two evolutionarily distant apicomplexan rhoptry secretion systems
Authors: Mageswaran Shrawan Kumar , Guérin Amandine , Theveny Liam M. , Chen William David , Martinez Matthew , Lebrun Maryse , Striepen Boris , Chang Yi-Wei 
Published: August 2021

AbstractParasites of the phylum Apicomplexa cause important diseases including malaria, cryptosporidiosis and toxoplasmosis. These intracellular pathogens inject the contents of an essential organelle, the rhoptry, into host cells to facilitate invasion and infection. However, the structure and mechanism of this eukaryotic secretion system remain elusive. Here, using cryo-electron tomography and subtomogram averaging, we report the conserved architecture of the rhoptry secretion system in the invasive stages of two evolutionarily distant apicomplexans, Cryptosporidium parvum and Toxoplasma gondii. In both species, we identify helical filaments, which appear to shape and compartmentalize the rhoptries, and an apical vesicle (AV), which facilitates docking of the rhoptry tip at the parasite’s apical region with the help of an elaborate ultrastructure named the rhoptry secretory apparatus (RSA); the RSA anchors the AV at the parasite plasma membrane. Depletion of T. gondii Nd9, a protein required for rhoptry secretion, disrupts the RSA ultrastructure and AV-anchoring. Moreover, T. gondii contains a line of AV-like vesicles, which interact with a pair of microtubules and accumulate towards the AV, leading to a working model for AV-reloading and discharging of multiple rhoptries. Together, our analyses provide an ultrastructural framework to understand how these important parasites deliver effectors into host cells.
A broadly neutralizing humanized ACE2-targeting antibody against SARS-CoV-2 variants
Authors: Du Yanyun , Shi Rui , Zhang Ying , Duan Xiaomin , Li Li , Zhang Jing , Wang Fengze , Zhang Ruixue , Shen Hao , Wang Yue , Wu Zheng , Peng Qianwen , Pan Ting , Sun Wanwei , Huang Weijin , Feng Yue , Feng Hui , Xiao Junyu , Tan Wenjie , Wang Youchun , Wang Chenhui , Yan Jinghua 
Published: August 2021

AbstractThe successive emergences and accelerating spread of novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) lineages and evolved resistance to some ongoing clinical therapeutics increase the risks associated with the coronavirus disease 2019 (COVID-19) pandemic. An urgent intervention for broadly effective therapies to limit the morbidity and mortality of COVID-19 and future transmission events from SARS-related coronaviruses (SARSr-CoVs) is needed. Here, we isolate and humanize an angiotensin-converting enzyme-2 (ACE2)-blocking monoclonal antibody (MAb), named h11B11, which exhibits potent inhibitory activity against SARS-CoV and circulating global SARS-CoV-2 lineages. When administered therapeutically or prophylactically in the hACE2 mouse model, h11B11 alleviates and prevents SARS-CoV-2 replication and virus-induced pathological syndromes. No significant changes in blood pressure and hematology chemistry toxicology were observed after injections of multiple high dosages of h11B11 in cynomolgus monkeys. Analysis of the structures of the h11B11/ACE2 and receptor-binding domain (RBD)/ACE2 complexes shows hindrance and epitope competition of the MAb and RBD for the receptor. Together, these results suggest h11B11 as a potential therapeutic countermeasure against SARS-CoV, SARS-CoV-2, and escape variants.
Deep forest model for diagnosing COVID-19 from routine blood tests
Authors: AlJame Maryam , Imtiaz Ayyub , Ahmad Imtiaz , Mohammed Ameer 
Published: August 2021

AbstractThe Coronavirus Disease 2019 (COVID-19) global pandemic has threatened the lives of people worldwide and posed considerable challenges. Early and accurate screening of infected people is vital for combating the disease. To help with the limited quantity of swab tests, we propose a machine learning prediction model to accurately diagnose COVID-19 from clinical and/or routine laboratory data. The model exploits a new ensemble-based method called the deep forest (DF), where multiple classifiers in multiple layers are used to encourage diversity and improve performance. The cascade level employs the layer-by-layer processing and is constructed from three different classifiers: extra trees, XGBoost, and LightGBM. The prediction model was trained and evaluated on two publicly available datasets. Experimental results show that the proposed DF model has an accuracy of 99.5%, sensitivity of 95.28%, and specificity of 99.96%. These performance metrics are comparable to other well-established machine learning techniques, and hence DF model can serve as a fast screening tool for COVID-19 patients at places where testing is scarce.
Predicting the development of normal tension glaucoma and related risk factors in normal tension glaucoma suspects
Authors: Park Hae-Young Lopilly , Shin Da Young , Jeon Soo Ji , Kim Yong-Chan , Jung Younhea , Kim Eun Kyoung , Shin Hye-Young , Jung Kyoung In , Choi Jin A. , Lee Na Young , Hong Seung Woo , Park Chan Kee 
Published: August 2021

AbstractThis study investigated the predicted risk factors for the development of normal-tension glaucoma (NTG) in NTG suspects. A total of 684 eyes of 379 NTG suspects who were followed-up for at least 5 years were included in the study. NTG suspects were those having (1) intraocular pressure within normal range, (2) suspicious optic disc (neuroretinal rim thinning) or enlarged cup-to-disc ratio (≥ 0.6), but without definite localized retinal nerve fiber layer (RNFL) defects on red-free disc/fundus photographs, and (3) normal visual field (VF). Demographic, systemic, and ocular characteristics were determined at the time of the first visit via detailed history-taking and examination of past medical records. Various ocular parameters were assess using spectral-domain optical coherence tomography and Heidelberg retinal tomography. Conversion to NTG was defined either by the presence of a new localized RNFL defect at the superotemporal or inferotemporal region on disc/fundus red-free photographs, or presence of a glaucomatous VF defect on pattern standard deviation plots on two consecutive tests. Hazard ratios were calculated with the Cox proportional hazard model. In total, 86 (12.6%) of the 684 NTG suspects converted to NTG during the follow-up period of 69.39 ± 7.77 months. Significant (P < 0.05, Cox regression) risk factors included medication for systemic hypertension, longer axial length, worse baseline VF parameters, thinner baseline peripapillary RNFL, greater disc torsion, and lamina cribrosa (LC) thickness < 180.5 μm (using a cut-off value obtained by regression analysis). Significant (P < 0.05, Cox regression) risk factors in the non-myopic NTG suspects included medication for systemic hypertension and a LC thinner than the cut-off value. Significant (P < 0.05, Cox regression) risk factors in the myopic NTG suspects included greater disc torsion. The results indicated that 12.6% of NTG suspects converted to NTG during the 5–6-year follow-up period. NTG suspects taking medication for systemic hypertension, disc torsion of the optic disc in the inferotemporal direction, and thinner LC of the optic nerve head at baseline were at greater risk of NTG conversion. Related baseline risk factors were different between myopic and non-myopic NTG suspects.
Choosing a treatment method for post-catheterization pseudoaneurysms guided by the late to early velocity index
Authors: Kurzawski Jacek , Zandecki Lukasz , Janion-Sadowska Agnieszka , Piatek Lukasz , Jaroszynska Anna , Domagala Szymon , Sadowski Marcin , Baranska Edyta 
Published: August 2021

AbstractUltrasound-guided thrombin injection (UGTI) is often the first-line treatment for iatrogenic post-catheterization pseudoaneurysms (psA). There are also first reports of the use of biologically derived tissue glues (TG) instead of sole thrombin especially when UGTI was unsuccessful or in case of psA recurrence. Previously, we have established that a late to early velocity index (LEVI) < 0.2 could be a predictor of an increased risk of psA recurrence after standard UGTI. In this paper, we report our first experiences when the choice of the first-line treatment method was based on LEVI assessment. From May 2017 till January 2020 we included 36 patients with psA. Of them, 10 had LEVI < 0.2 and they underwent ultrasound-guided tissue glue injection (UGTGI) with biological TG and 26 had LEVI > 0.2 and they underwent UGTI. The injection set containing human thrombin and fibrinogen was used for UGTGI. Bovine thrombin was used for UGTI. The success rate was 100% and no psA recurrence was detected during a 2-week follow-up. It was significantly better when compared to the expected recurrence rates based on our previous 14 years of experience (0% vs. 13%, p = 0.01). All complications (10% in the UGTGI group and 15% in the UGTI group) were mild and transient and included clinical symptoms of paresthesia, numbness, tingling, or pain. Their rates were comparable to the rates we previously reported. No significant differences in other characteristics were observed. The approach to choose the first-line treatment method for iatrogenic psA based on LEVI is encouraging. It may increase the success rate and avoid unnecessary repetition of the procedure, without increasing complication rate while keeping costs of the procedure reasonable.
Impact of anthropogenic activities on morphological and deposition flux changes in the Pearl River Estuary, China
Authors: Wei Xing , Cai Shuqun , Zhan Weikang 
Published: August 2021

AbstractThe evolution of the Pearl River Estuary (PRE), China in recent decades has been dominated by human activities. Historical admiralty charts and remote sensing images indicated that from 1936 to 2017, the tidal flat area and water area decreased by 23.6 × 107 m2 and 60.7 × 107 m2, respectively. The average advancing rate of the coastline of the PRE to the sea from 1972 to 2017 reached approximately 64.8 m/year, which is several times or even dozens of times that since the mid-Holocene. Land reclamation was the main reason for the dramatic changes in the water area and coastline. Although the water volume of the PRE showed a decreasing trend from 1936 to 2017, the water volume reduction rates for 1996–2005 and 2005–2017 were only 29% (1.27 × 107 m3/year) and 12% (0.53 × 107 m3/year), respectively, of that for 1936–1972. The combined influences of channel dredging, sand mining, and sediment load reduction caused by dam construction have contributed to this change. From the perspective of the filling up of the estuary, channel dredging, sand mining, and dam construction in the river basin are beneficial for prolonging the life of the estuary.
Exploration of bioconvection flow of MHD thixotropic nanofluid past a vertical surface coexisting with both nanoparticles and gyrotactic microorganisms
Authors: Koriko Olubode Kolade , Shah Nehad Ali , Saleem S. , Chung Jae Dong , Omowaye Adeola John , Oreyeni Tosin 
Published: August 2021

AbstractThis communication presents analysis of gravity-driven flow of a thixotropic fluid containing both nanoparticles and gyrotactic microorganisms along a vertical surface. To further describe the transport phenomenon, special cases of active and passive controls of nanoparticles are investigated. The governing partial differential equations of momentum, energy, nanoparticles concentration, and density of gyrotactic microorganisms equations are converted and parameterized into system of ordinary differential equations and the series solutions are obtained through Optimal Homotopy Analysis Method (OHAM). The related important parameters are tested and shown on the velocity, temperature, concentration and density of motile microorganisms profiles. It is observed that for both cases of active and passive control of nanoparticles, incremental values of thermophoretic parameters corresponds to decrease in the velocity distributions and augment the temperature distributions.
Examining Social Networks in Older Adults: What Predicts Communicative Participation?
Authors: Meeker Melanie , McCullough Kimberly C. , McCullough Gary H. , Akpanudo Usenime 
Published: August 2021

Purpose
Social isolation is linked to cognitive decline and depression, which can be risk factors for developing dementia. The purpose of this study was to determine which of a variety of factors were associated with communicative participation as measured by social network size.

Method
Three hundred thirty-seven adults aged 65 years or older were administered assessments to evaluate social network size, cognition, hearing handicap, and quality of communicative participation.

Results
Cognition, education, living setting, and quality of communication life were associated to varying degrees with the construct of communicative participation as measured by social network size.

Conclusion
Assessment of these variables, along with early identification of cognitive decline, could play an important role in identifying elderly individuals at risk for limitations in communicative participation and associated consequences.
Uncertainties in the pasta-phase properties of catalysed neutron stars
Authors: Dinh Thi H. , Carreau T. , Fantina A. F. , Gulminelli F. 
Published: August 2021

Context. The interior of a neutron star is expected to exhibit different states of matter. In particular, complex non-spherical configurations known as ‘pasta’ phases may exist at the highest densities in the inner crust, potentially having an impact on different neutron-star phenomena.
Aims. We study the properties of the pasta phase and the uncertainties in the pasta observables which are due to our incomplete knowledge of the nuclear energy functional.
Methods. To this aim, we employed a compressible liquid-drop model approach with surface parameters optimised either on experimental nuclear masses or theoretical calculations. To assess the model uncertainties, we performed a Bayesian analysis by largely varying the model parameters using uniform priors, and generating posterior distributions with filters accounting for both our present low-density nuclear physics knowledge and high-density neutron-star physics constraints.
Results. Our results show that the nuclear physics constraints, such as the neutron-matter equation of state at very low density and the experimental mass measurements, are crucial in determining the crustal and pasta observables. Accounting for all constraints, we demonstrate that the presence of pasta phases is robustly predicted in an important fraction of the inner crust. We estimate the relative crustal thickness associated with pasta phases as Rpasta/Rcrust = 0.128 ± 0.047 and the relative moment of inertia as Ipasta/Icrust = 0.480 ± 0.137.
Conclusions. Our findings indicate that the surface and curvature parameters are more influential than the bulk parameters for the description of the pasta observables. We also show that using a surface tension that is inconsistent with the bulk functional leads to an underestimation of both the average values and the uncertainties in the pasta properties, thus highlighting the importance of a consistent calculation of the nuclear functional.
A Domino Heck Coupling–Cyclization–Dehydrogenative Strategy for the One-Pot Synthesis of Quinolines
Authors: Ghora Santanu , Sreenivasulu Chinnabattigalla , Satyanarayana Gedu 
Published: August 2021

AbstractAn efficient, one-pot, domino synthesis of quinolines via the coupling of iodoanilines with allylic alcohols facilitated by palladium catalysis is described. The overall synthetic process involves an intermolecular Heck coupling between 2-iodoanilines and allylic alcohols, intramolecular condensation of in situ generated ketones with an internal amine functional group, and a dehydrogenation sequence. Notably, this protocol occurs in water as a green solvent. Significantly, the method exhibits broad substrate scope and is applied for the synthesis of deuterated quinolines through a deuterium-exchange process.
Recent Progress in Amination Enabled by Transition-Metal-Free C(sp2)–O/C(sp2)–S Bond Cleavage Strategy
Authors: Yang Xin-Ge , Wang Xue-Qiang , Li Shen-Huan , Long Cheng-Yu 
Published: August 2021

AbstractRecently, intense efforts have been dedicated to the development of novel synthetic strategies to access aromatic amines due to their importance in the pharmaceuticals, agrochemicals, materials, and natural product areas. Although numerous transition-metal-catalyzed C–N formation strategies have been described for the preparation of aromatic amines in the past few decades, complementary methods under transition-metal-free conditions are still required. We present the recent advances in the exploration of innovative amination approaches via C(sp2)–O/C(sp2)–S bond cleavage in this review.1	Introduction2	Stoichiometric Base-Promoted Amination3	Base-Catalyzed Amination4	Photoredox-Catalyzed Amination5	Acid-Promoted Amination6	Conclusion and Perspectives