bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multi-ancestry fine mapping implicates OAS1 splicing in risk of severe COVID-19
Authors: Huffman Jennifer E. , Butler-Laporte Guillaume , Khan Atlas , Pairo-Castineira Erola , Drivas Theodore G. , Peloso Gina M. , Nakanishi Tomoko ,   COVID-19 Host Genetics Initiative, Ganna Andrea , Verma Anurag , Baillie J. Kenneth , Kiryluk Krzysztof , Richards J. Brent , Zeberg Hugo 
Published: January 2022

AbstractThe OAS1/2/3 cluster has been identified as a risk locus for severe COVID-19 among individuals of European ancestry, with a protective haplotype of approximately 75 kilobases (kb) derived from Neanderthals in the chromosomal region 12q24.13. This haplotype contains a splice variant of OAS1, which occurs in people of African ancestry independently of gene flow from Neanderthals. Using trans-ancestry fine-mapping approaches in 20,779 hospitalized cases, we demonstrate that this splice variant is likely to be the SNP responsible for the association at this locus, thus strongly implicating OAS1 as an effector gene influencing COVID-19 severity.
SARS-CoV-2 infection and COVID-19 vaccination rates in pregnant women in Scotland
Authors: Stock Sarah J. , Carruthers Jade , Calvert Clara , Denny Cheryl , Donaghy Jack , Goulding Anna , Hopcroft Lisa E. M. , Hopkins Leanne , McLaughlin Terry , Pan Jiafeng , Shi Ting , Taylor Bob , Agrawal Utkarsh , Auyeung Bonnie , Katikireddi Srinivasa Vittal , McCowan Colin , Murray Josie , Simpson Colin R. , Robertson Chris , Vasileiou Eleftheria , Sheikh Aziz , Wood Rachael 
Published: January 2022

AbstractPopulation-level data on COVID-19 vaccine uptake in pregnancy and SARS-CoV-2 infection outcomes are lacking. We describe COVID-19 vaccine uptake and SARS-CoV-2 infection in pregnant women in Scotland, using whole-population data from a national, prospective cohort. Between the start of a COVID-19 vaccine program in Scotland, on 8 December 2020 and 31 October 2021, 25,917 COVID-19 vaccinations were given to 18,457 pregnant women. Vaccine coverage was substantially lower in pregnant women than in the general female population of 18−44 years; 32.3% of women giving birth in October 2021 had two doses of vaccine compared to 77.4% in all women. The extended perinatal mortality rate for women who gave birth within 28 d of a COVID-19 diagnosis was 22.6 per 1,000 births (95% CI 12.9−38.5; pandemic background rate 5.6 per 1,000 births; 452 out of 80,456; 95% CI 5.1−6.2). Overall, 77.4% (3,833 out of 4,950; 95% CI 76.2−78.6) of SARS-CoV-2 infections, 90.9% (748 out of 823; 95% CI 88.7−92.7) of SARS-CoV-2 associated with hospital admission and 98% (102 out of 104; 95% CI 92.5−99.7) of SARS-CoV-2 associated with critical care admission, as well as all baby deaths, occurred in pregnant women who were unvaccinated at the time of COVID-19 diagnosis. Addressing low vaccine uptake rates in pregnant women is imperative to protect the health of women and babies in the ongoing pandemic.
CellRank for directed single-cell fate mapping
Authors: Lange Marius , Bergen Volker , Klein Michal , Setty Manu , Reuter Bernhard , Bakhti Mostafa , Lickert Heiko , Ansari Meshal , Schniering Janine , Schiller Herbert B. , Pe’er Dana , Theis Fabian J. 
Published: January 2022

AbstractComputational trajectory inference enables the reconstruction of cell state dynamics from single-cell RNA sequencing experiments. However, trajectory inference requires that the direction of a biological process is known, largely limiting its application to differentiating systems in normal development. Here, we present CellRank (https://cellrank.org) for single-cell fate mapping in diverse scenarios, including regeneration, reprogramming and disease, for which direction is unknown. Our approach combines the robustness of trajectory inference with directional information from RNA velocity, taking into account the gradual and stochastic nature of cellular fate decisions, as well as uncertainty in velocity vectors. On pancreas development data, CellRank automatically detects initial, intermediate and terminal populations, predicts fate potentials and visualizes continuous gene expression trends along individual lineages. Applied to lineage-traced cellular reprogramming data, predicted fate probabilities correctly recover reprogramming outcomes. CellRank also predicts a new dedifferentiation trajectory during postinjury lung regeneration, including previously unknown intermediate cell states, which we confirm experimentally.
Covalent coupling of Spike’s receptor binding domain to a multimeric carrier produces a high immune response against SARS-CoV-2
Authors:   Argentinian AntiCovid Consortium, Berguer Paula M. , Blaustein Matías , Bredeston Luis M. , Craig Patricio O. , D’Alessio Cecilia , Elias Fernanda , Farré Paola C. , Fernández Natalia B. , Gentili Hernán G. , Gándola Yamila B. , Gasulla Javier , Gudesblat Gustavo E. , Herrera María G. , Ibañez Lorena I. , Idrovo-Hidalgo Tommy , Nadra Alejandro D. , Noseda Diego G. , Paván Carlos H. , Pavan María F. , Pignataro María F. , Roman Ernesto A. , Ruberto Lucas A. M. , Rubinstein Natalia , Sanchez María V. , Santos Javier , Wetzler Diana E. , Zelada Alicia M. 
Published: January 2022

AbstractThe receptor binding domain (RBD) of the Spike protein from SARS-CoV-2 is a promising candidate to develop effective COVID-19 vaccines since it can induce potent neutralizing antibodies. We have previously reported the highly efficient production of RBD in Pichia pastoris, which is structurally similar to the same protein produced in mammalian HEK-293T cells. In this work we designed an RBD multimer with the purpose of increasing its immunogenicity. We produced multimeric particles by a transpeptidation reaction between RBD expressed in P. pastoris and Lumazine Synthase from Brucella abortus (BLS), which is a highly immunogenic and very stable decameric 170 kDa protein. Such particles were used to vaccinate mice with two doses 30 days apart. When the particles ratio of RBD to BLS units was high (6–7 RBD molecules per BLS decamer in average), the humoral immune response was significantly higher than that elicited by RBD alone or by RBD-BLS particles with a lower RBD to BLS ratio (1–2 RBD molecules per BLS decamer). Remarkably, multimeric particles with a high number of RBD copies elicited a high titer of neutralizing IgGs. These results indicate that multimeric particles composed of RBD covalent coupled to BLS possess an advantageous architecture for antigen presentation to the immune system, and therefore enhancing RBD immunogenicity. Thus, multimeric RBD-BLS particles are promising candidates for a protein-based vaccine.
Cryoprotectant treatment tests on three morphologically diverse marine dinoflagellates and the cryopreservation of Breviolum sp. (Symbiodiniaceae)
Authors: Kihika Joseph Kanyi , Wood Susanna A. , Rhodes Lesley , Smith Kirsty F. , Thompson Lucy , Challenger Sarah , Ryan Ken G. 
Published: January 2022

AbstractDinoflagellates are among the most diverse group of microalgae. Many dinoflagellate species have been isolated and cultured, and these are used for scientific, industrial, pharmaceutical, and agricultural applications. Maintaining cultures is time-consuming, expensive, and there is a risk of contamination or genetic drift. Cryopreservation offers an efficient means for their long-term preservation. Cryopreservation of larger dinoflagellate species is challenging and to date there has been only limited success. In this study, we explored the effect of cryoprotectant agents (CPAs) and freezing methods on three species: Vulcanodinium rugosum, Alexandrium pacificum and Breviolum sp. A total of 12 CPAs were assessed at concentrations between 5 and 15%, as well as in combination with dimethyl sulfoxide (DMSO) and other non-penetrating CPAs. Two freezing techniques were employed: rapid freezing and controlled-rate freezing. Breviolum sp. was successfully cryopreserved using 15% DMSO. Despite exploring different CPAs and optimizing the freezing techniques, we were unable to successfully cryopreserve V. rugosum and A. pacificum. For Breviolum sp. there was higher cell viability (45.4 ± 2.2%) when using the controlled-rate freezing compared to the rapid freezing technique (10.0 ± 2.8%). This optimized cryopreservation protocol will be of benefit for the cryopreservation of other species from the family Symbiodiniaceae.
Modulated anti-VEGF therapy under the influence of lipid metabolizing proteins in Age related macular degeneration: a pilot study
Authors: Sharma Kaushal , Battu Priya , Singh Ramandeep , Sharma Suresh Kumar , Anand Akshay 
Published: January 2022

AbstractAge-related macular degeneration (AMD) is a devastating retinal disease that results in irreversible vision loss in the aged population. The complex genetic nature and degree of genetic penetrance require a redefinition of the current therapeutic strategy for AMD. We aimed to investigate the role of modifiers for current anti-VEGF therapy especially for non-responder AMD patients. We recruited 78 wet AMD cases (out of 278 AMD patients) with their socio-demographic and treatment regimen. Serum protein levels were estimated by ELISA in AMD patients. Data pertaining to the number of anti-VEGF injections given (in 1 year) along with clinical images (FFA and OCT) of AMD patients were also included. Visual acuity data (logMAR) for 46 wet AMD cases out of a total of 78 patients were also retrieved to examine the response of anti-VEGF injections in wet AMD cases. Lipid metabolizing genes (LIPC and APOE) have been identified as chief biomarkers for anti-VEGF response in AMD patients. Both genotypes ‘CC’ and ‘GC’ of LIPC have found to be associated with a number of anti-VEGF injections in AMD patients which could influence the expression of B3GALTL,HTRA1, IER3, LIPC and SLC16A8 proteins in patients bearing both genotypes as compared to reference genotype. Elevated levels of APOE were also observed in group 2 wet AMD patients as compared to group 1 suggesting the significance of APOE levels in anti-VEGF response. The genotype of B3GALTL has also been shown to have a significant association with the number of anti-VEGF injections. Moreover, visual acuity of group 1 (≤ 4 anti-VEGF injections/year) AMD patients was found significantly improved after 3 doses of anti-VEGF injections and maintained longitudinally as compared to groups 2 and 3. Lipid metabolising genes may impact the outcome of anti-VEGF AMD treatment.
Biochemical and structural characterization of quizalofop-resistant wheat acetyl-CoA carboxylase
Authors: Bough Raven , Dayan Franck E. 
Published: January 2022

AbstractA novel nucleotide mutation in ACC1 resulting in an alanine to valine amino acid substitution in acetyl-CoA carboxylase (ACCase) at position 2004 of the Alopecurus myosuroides reference sequence (A2004V) imparts quizalofop resistance in wheat. Genotypes endowed with the homozygous mutation in one or two ACC1 homoeologs are seven- and 68-fold more resistant to quizalofop than a wildtype winter wheat in greenhouse experiments, respectively. In vitro ACCase activities in soluble protein extracts from these varieties are 3.8- and 39.4-fold more resistant to quizalofop with the homozygous mutation in either one or two genomes, relative to the wildtype. The A2004V mutation does not alter the specific activity of wheat ACCase, suggesting that this resistance trait does not affect the catalytic functions of ACCase. Modeling of wildtype and quizalofop-resistant wheat ACCase demonstrates that the A2004V amino acid substitution causes a reduction in the volume of the binding pocket that hinders quizalofop’s interaction with ACCase. Docking studies confirm that the mutation reduces the binding affinity of quizalofop. Interestingly, the models suggest that the A2004V mutation does not affect haloxyfop binding. Follow up in vivo and in vitro experiments reveal that the mutation, in fact, imparts negative cross-resistance to haloxyfop, with quizalofop-resistant varieties exhibiting higher sensitivity to haloxyfop than the wildtype winter wheat line.
Electrochemical performance of composite electrodes based on rGO, Mn/Cu metal–organic frameworks, and PANI
Authors: Le Quoc Bao , Nguyen Thanh-Huong , Fei Haojie , Bubulinca Constantin , Munster Lukas , Bugarova Nikola , Micusik Matej , Kiefer Rudolf , Dao Tran Trong , Omastova Maria , Kazantseva Natalia E. , Saha Petr 
Published: January 2022

AbstractBenzendicarboxylic acid (BDC)-based metal–organic frameworks (MOFs) have been widely utilized in various applications, including supercapacitor electrode materials. Manganese and copper have solid diamond frames formed with BDC linkers among transition metals chosen for MOF formation. They have shown the possibility to enlarge capacitance at different combinations of MOFs and polyaniline (PANI). Herein, reduced graphene oxide (rGO) was used as the matrix to fabricate electrochemical double-layer SCs. PANI and Mn/Cu-MOF's effect on the properties of electrode materials was investigated through electrochemical analysis. As a result, the highest specific capacitance of about 276 F/g at a current density of 0.5 A/g was obtained for rGO/Cu-MOF@PANI composite.
Bivalent single domain antibody constructs for effective neutralization of Venezuelan equine encephalitis
Authors: Liu Jinny L. , Zabetakis Dan , Gardner Christina L. , Burke Crystal W. , Glass Pamela J. , Webb Emily M. , Shriver-Lake Lisa C. , Anderson George P. , Weger-Lucarelli James , Goldman Ellen R. 
Published: January 2022

AbstractVenezuelan equine encephalitis virus (VEEV) is a mosquito borne alphavirus which leads to high viremia in equines followed by lethal encephalitis and lateral spread to humans. In addition to naturally occurring outbreaks, VEEV is a potential biothreat agent with no approved human vaccine or therapeutic currently available. Single domain antibodies (sdAb), also known as nanobodies, have the potential to be effective therapeutic agents. Using an immune phage display library derived from a llama immunized with an equine vaccine that included inactivated VEEV, five sdAb sequence families were identified that showed varying ability to neutralize VEEV. One of the sequence families had been identified previously in selections against chikungunya virus, a related alphavirus of public health concern. A key advantage of sdAb is the ability to optimize properties such as neutralization capacity through protein engineering. Neutralization of VEEV was improved by two orders of magnitude by genetically linking sdAb. One of the bivalent constructs showed effective neutralization of both VEEV and chikungunya virus. Several of the bivalent constructs neutralized VEEV in cell-based assays with reductions in the number of plaques by 50% at protein concentrations of 1 ng/mL or lower, making future evaluation of their therapeutic potential compelling.
eNAMPT neutralization reduces preclinical ARDS severity via rectified NFkB and Akt/mTORC2 signaling
Authors: Bermudez Tadeo , Sammani Saad , Song Jin H. , Hernon Vivian Reyes , Kempf Carrie L. , Garcia Alexander N. , Burt Jessica , Hufford Matthew , Camp Sara M. , Cress Anne E. , Desai Ankit A. , Natarajan Viswanathan , Jacobson Jeffrey R. , Dudek Steven M. , Cancio Leopoldo C. , Alvarez Julie , Rafikov Ruslan , Li Yansong , Zhang Donna D. , Casanova Nancy G. , Bime Christian , Garcia Joe G. N. 
Published: January 2022

AbstractDespite encouraging preclinical data, therapies to reduce ARDS mortality remains a globally unmet need, including during the COVID-19 pandemic. We previously identified extracellular nicotinamide phosphoribosyltransferase (eNAMPT) as a novel damage-associated molecular pattern protein (DAMP) via TLR4 ligation which regulates inflammatory cascade activation. eNAMPT is tightly linked to human ARDS by biomarker and genotyping studies in ARDS subjects. We now hypothesize that an eNAMPT-neutralizing mAb will significantly reduce the severity of ARDS lung inflammatory lung injury in diverse preclinical rat and porcine models. Sprague Dawley rats received eNAMPT mAb intravenously following exposure to intratracheal lipopolysaccharide (LPS) or to a traumatic blast (125 kPa) but prior to initiation of ventilator-induced lung injury (VILI) (4 h). Yucatan minipigs received intravenous eNAMPT mAb 2 h after initiation of septic shock and VILI (12 h). Each rat/porcine ARDS/VILI model was strongly associated with evidence of severe inflammatory lung injury with NFkB pathway activation and marked dysregulation of the Akt/mTORC2 signaling pathway. eNAMPT neutralization dramatically reduced inflammatory indices and the severity of lung injury in each rat/porcine ARDS/VILI model (~ 50% reduction) including reduction in serum lactate, and plasma levels of eNAMPT, IL-6, TNFα and Ang-2. The eNAMPT mAb further rectified NFkB pathway activation and preserved the Akt/mTORC2 signaling pathway. These results strongly support targeting the eNAMPT/TLR4 inflammatory pathway as a potential ARDS strategy to reduce inflammatory lung injury and ARDS mortality.
Construction and validation of a risk prediction model for clinical axillary lymph node metastasis in T1–2 breast cancer
Authors: Luo Na , Wen Ying , Zou Qiongyan , Ouyang Dengjie , Chen Qitong , Zeng Liyun , He Hongye , Anwar Munawar , Qu Limeng , Ji Jingfen , Yi Wenjun 
Published: January 2022

AbstractThe current diagnostic technologies for assessing the axillary lymph node metastasis (ALNM) status accurately in breast cancer (BC) remain unsatisfactory. Here, we developed a diagnostic model for evaluating the ALNM status using a combination of mRNAs and the T stage of the primary tumor as a novel biomarker. We collected relevant information on T1–2 BC from public databases. An ALNM prediction model was developed by logistic regression based on the screened signatures and then internally and externally validated. Calibration curves and the area under the curve (AUC) were employed as performance metrics. The prognostic value and tumor immune infiltration of the model were also determined. An optimal diagnostic model was created using a combination of 11 mRNAs and T stage of the primary tumor and showed high discrimination, with AUCs of 0.828 and 0.746 in the training sets. AUCs of 0.671 and 0.783 were achieved in the internal validation cohorts. The mean external AUC value was 0.686 and ranged between 0.644 and 0.742. Moreover, the new model has good specificity in T1 and hormone receptor-negative/human epidermal growth factor receptor 2- negative (HR−/HER2−) BC and good sensitivity in T2 BC. In addition, the risk of ALNM and 11 mRNAs were correlated with the infiltration of M2 macrophages, as well as the prognosis of BC. This novel prediction model is a useful tool to identify the risk of ALNM in T1–2 BC patients, particularly given that it can be used to adjust surgical options in the future.
A digital twin auxiliary approach based on adaptive sparse attention network for diesel engine fault diagnosis
Authors: Jiang Jiajie , Li Hui , Mao Zhiwei , Liu Fengchun , Zhang Jinjie , Jiang Zhinong , Li He 
Published: January 2022

AbstractCondition monitoring and fault diagnosis of diesel engines are of great significance for safety production and maintenance cost control. The digital twin method based on data-driven and physical model fusion has attracted more and more attention. However, the existing methods lack deeper integration and optimization facing complex physical systems. Most of the algorithms based on deep learning transform the data into the substitution of the physical model. The lack of interpretability of the deep learning diagnosis model limits its practical application. The attention mechanism is gradually developed to access interpretability. In this study, a digital twin auxiliary approach based on adaptive sparse attention network for diesel engine fault diagnosis is proposed with considering its signal characteristics of strong angle domain correlation and transient non-stationary, in which a new soft threshold filter is designed to draw more attention to multi decentralized local fault information dynamically in real time. Based on this attention mechanism, the distribution of fault information in the original signal can be better visualized to help explain the fault mechanism. The valve failure experiment on a diesel engine test rig is conducted, of which the results show that the proposed adaptive sparse attention mechanism model has better training efficiency and clearer interpretability on the premise of maintaining performance.
A high‐efficiency and stable perovskite solar cell fabricated in ambient air using a polyaniline passivation layer
Authors: Kim Dong In , Lee Ji Won , Jeong Rak Hyun , Boo Jin-Hyo 
Published: January 2022

AbstractOver the past number of years, the power conversion efficiency of perovskite solar cells has remained at 25.5%, reflecting a respectable result for the general incorporation of organometallic trihalide perovskite solar cells. However, perovskite solar cells still suffer from long-term stability issues. Perovskite decomposes upon exposure to moisture, thermal, and UV-A light. Studies related to this context have remained ongoing. Recently, research was mainly conducted on the stability of perovskite against non-radiative recombination. This study improved a critical instability in perovskite solar cells arising from non-radiative recombination and UV-A light using a passivation layer. The passivation layer comprised a polyaniline (PANI) polymer as an interfacial modifier inserted between the active layer and the electron transport layer. Accordingly, the UV-A light did not reach the active layer and confined the Pb2+ ions at PANI passivation layer. This study optimized the perovskite solar cells by controlling the concentration, thickness and drying conditions of the PANI passivation layer. As a result, the efficiency of the perovskite solar cell was achieved 15.1% and showed over 84% maintain in efficiency in the ambient air for one month using the 65 nm PANI passivation layer.