bluuebunny/crossref_metadata_2025_split huggingface dataset:
Utilization of a SARS-CoV-2 Variant Assay for the Rapid Differentiation of Omicron and Delta
Authors: Barasch Nicholas , Iqbal Jameel , Coombs Marvin , Kazi Sofia , Wang-Rodriguez Jessica , Holodniy Mark , Gelman Michael 
Published: December 2021

AbstractThe emergence of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant (B.1.1.529), creates a diagnostic vacuum, since differentiation of Omicron from Delta relies on relatively slow next generation sequencing (NGS) technology delaying epidemiologic understanding and therapeutic intervention. The RUO SARS-CoV-2 Variant Set 1 Test (RSCov2V1) RT-PCR for detection of spike gene N501Y, E484K and del69-70 was designed to differentiate Alpha from Beta and Gamma variants. While Delta lacks these three variants, Omicron has the N501Y and del69-70 mutation. We submitted 88 samples for RSCov2V1 identifying 9 samples with the N501Y and del69-70 mutations while all other samples (79) were negative for all three variants. 9/9 samples with the del69-70 and N501Y were identified by NGS to be Omicron while 47/47 other samples assessed by NGS were confirmed to be Delta family variants. We demonstrate here that an immediately available RT-PCR assay for detection of spike gene N501Y and del69-70 can be utilized to rapidly differentiate Omicron from Delta variants in the proper epidemiologic context
Direct, Indirect and Mixed Methods of Health Education By Nurse and Its Impact on Type 2 Diabetes Patients: A Literature review
Authors: Akoit Emilia Erningwati , Rumambo Pandin Moses Glorino 
Published: December 2021

AbstractBackgroundDiabetes Mellitus (DM) is one of the chronic non-communicable diseases that has currently been very common, in particular Diabetes Mellitus type 2 that threatens public health. It has been included in the category of the six biggest causes of worldwide death, but self-control of treatment and obedience to self-care is still low. One of the influencing factors is related to the lack of knowledge. Providing ongoing health education is one of the solutions or efforts to strengthen knowledge in type 2 diabetes. The aim was to identify the various health education methods currently used by nurses and their impacts on type 2 DM. The method used is a literature review. The literature was searched on data based on Scopus, Web of Science, SAGE, CINAHL with the keywords “methods” or “interventions”, “education”, “health”, “nursing”, and “type 2 diabetes melitus. Fifteen (15) pieces of literature were considered to meet the criteria inclusion.ResultsThree (3) types of health education methods used by nurses were identified: 1). Direct health education refers to providing education by nurses to patients through training, coaching, interviews, Focus Group Discussion (FGD) and home visits; 2). Indirect Health Education - using mobile phones; 3). The mixed of direct health education and the use of mobile phone-based applications is carried out with the application of mobile health technology and nurse health coaching. The impact of providing health education by nurses to type 2 diabetic patients: increasing of knowledge, behavioral change on preventing diabetes complications, increasing self-efficacy, increasing self-care activities (diet management, physical activity, monitoring blood sugar levels, and foot care).Conclusionvarious methods of health education carried out by nurses currently have a positive impact on improving and increasing self-care management and efforts to prevent complications in type 2 diabetes.
Testing the phenotypic decanalization hypothesis: social determinants of hyperglycemia and type 2 diabetes in adult urban Argentinian population
Authors: Petino Zappala María Alejandra , Folguera Guillermo , Benitez-Vieyra Santiago 
Published: December 2021

AbstractType 2 diabetes, one of the major causes of death and disability worldwide, is characterized by problems in the homeostasis of blood glucose. Current preventive policies focus mainly on individual behaviors (diet, exercise, salt and alcohol consumption). Recent hypotheses state that the higher incidence of metabolic disease in some human populations may be related to phenotypic decanalization causing a heightened phenotypic variance in response to unusual or stressful environmental conditions, although the nature of these conditions is under debate. Our aim was to explore variability patterns of fasting blood glucose to test phenotypic decanalization as a possible explanation of heightened prevalence for type 2 diabetes in some groups and to detect variables associated with its variance using a nation-wide survey of Argentinian adult population. We found patterns of higher local variance for fasting glycemia associated with lower income and educational attainment. We detected no meaningful association of glycemia or its variability with covariates related to individual behaviors (diet, physical activity, salt or alcohol consumption). Our results were consistent with the decanalization hypothesis for fasting glycemia, which appears associated to socioeconomic disadvantage. We therefore propose changes in public policy and discuss the implications for data gathering and further analyses.
NetREx – Network-based Rice Expression Analysis Server for Abiotic Stress Conditions
Authors: Sircar Sanchari , Musaddi Mayank , Parekh Nita 
Published: December 2021

AbstractRecent focus on transcriptomic studies in food crops like rice, wheat and maize provide new opportunities to address issues related to agriculture and climate change. Re-analysis of such data available in public domain supplemented with annotations across molecular hierarchy can be of immense help to the plant research community, particularly co-expression networks representing transcriptionally coordinated genes that are often part of the same biological process. With this objective we have developed NetREx, a Network based Rice Expression Analysis Server, that hosts ranked co-expression networks of Oryza sativa using publicly available mRNA-seq data across uniform experimental conditions. It provides a range of interactable data viewers and modules for analysing user queried genes across different stress conditions (drought, flood, cold and osmosis) and hormonal treatments (abscisic and jasmonic acid) and tissues (root and shoot). Subnetworks of user-defined genes can be queried in preconstructed tissue-specific networks, allowing users to view the fold-change, module memberships, gene annotations and analysis of their neighborhood genes and associated pathways. The webserver also allows querying of orthologous genes from Arabidopsis, wheat, maize, barley, and sorghum. Here we demonstrate that NetREx can be used to identify novel candidate genes and tissue-specific interactions under stress conditions and can aid in the analysis and understanding of complex phenotypes linked to stress response in rice. Available at: https://bioinf.iiit.ac.in/netrex/index.html
Reduced infectivity but increased immune escape of the new SARS-CoV-2 variant of concern Omicron
Authors: Hu Jie , Peng Pai , Wu Kang , Long Quan-xin , Chen Juan , Wang Kai , Tang Ni , Huang Ai-long 
Published: December 2021

AbstractA new detected SARS-CoV-2 variant Omicron (B.1.1.529) had reported from more than 80 countries. In the past few weeks, a new wave of infection driven by Omicron is in progress. Omicron Spike (S) protein pseudotyped virus was used to determine the effect of S mutations on its capacity of infectivity and immune evasion. Our results showed the lower entry efficiency and less cleavage ability of Omicron than D614G variant. Pseudotype-based neutralizing assay was performed to analyze neutralizing antibodies elicited by previously infection or the RBD-based protein subunit vaccine ZF2001 against the Omicron variant. Sera sampled at around one month after symptom onset from 12 convalescents who were previously infected by SARS-CoV-2 original strain shows a more than 20-fold decrease of neutralizing activity against Omicron variant, when compared to D614G variant. Among 12 individuals vaccinated by RBD subunit vaccine, 58.3% (7/12) sera sampled at 15-60 days after 3rd-dose vaccination did not neutralize Omicron. Geometric mean titers (GMTs, 50% inhibitory dose [ID50]) of these sera against Omicron were 9.4-fold lower than against D614G. These results suggested a higher risk of Omicron breakthrough infections and reduced efficiency of the protective immunity elicited by existing vaccines. There are important implications about the modification and optimization of the current epidemic prevention and control including vaccine strategies and therapeutic antibodies against Omicron variant.
Strain dependent structural effects and in vivo efficacy of enterovirus-D68 inhibitors
Authors: Lane Thomas , Fu Jianing , Sherry Barbara , Tarbet Bart , Hurst Brett L. , Riabova Olga , Kazakova Elena , Egorova Anna , Clarke Penny , Leser J. Smith , Frost Joshua , Rudy Michael , Tyler Ken , Klose Thomas , Kuhn Richard J. , Makarov Vadim , Ekins Sean 
Published: December 2021

AbstractAcute flaccid myelitis (AFM) leads to loss of limb control in young children and is likely due to Enterovirus-D68 (EV-D68), for which there is no current treatment. We have developed a lead isoxazole-3-carboxamide analog of pleconaril (11526092) which displayed potent inhibition of the pleconaril-resistant CVB3-Woodruff (IC50 6-20 nM), EV-D68 (IC50 58 nM), and other enteroviruses. A mouse respiratory model of EV-D68 infection, in which pleconaril is inactive, showed decreased viremia of 3 log units as well as statistically significant 1 log reduction in lung titer reduction at day 5 after treatment with 11526092. A cryo-electron microscopy (cryo-EM) structure of EV-D68 in complex with 11526092 suggests that the increased potency may be due to additional hydrophobic interactions. Cryo-EM structures of 11526092 and pleconaril demonstrate destabilization of EV-D68 (MO strain) compared to the previously described stabilization of EV-D68 (Fermon strain) with pleconaril, illustrating clear strain dependent mechanisms of this molecule. 11526092 represents a more potent inhibitor in vitro with in vivo efficacy providing a potential future treatment for EV-D68 and AFM, suggesting an improvement over pleconaril for further optimization.One-Sentence Summary11526092 demonstrates protein destabilization, improved in vitro potency and in vivo efficacy when compared with pleconaril against EV-D68.
Arachnoid granulations may be protective against the development of shunt dependent chronic hydrocephalus after aneurysm subarachnoid hemorrhage
Authors: Almohaimede Khaled , Zaccagna Fulvio , Kumar Ashish , da Costa Leodante , Wong Erin , Heyn Chris , Kapadia Anish 
Published: December 2021

AbstractBackground and PurposeChronic hydrocephalus may develop as a sequela of aneurysmal subarachnoid hemorrhage, requiring long-term cerebrospinal fluid shunting. Several clinical predictors of chronic hydrocephalus and shunt dependence have been proposed. However, no anatomical predictors have been identified.Materials and MethodsA retrospective cohort study was performed including 61 patients with aneurysmal subarachnoid hemorrhage. Clinical characteristics were noted for each patient including presentation World Federation of Neurosurgical Societies grade, modified Fischer grade, aneurysm characteristics, requirement for acute and chronic cerebrospinal fluid diversion, and 3-month modified Rankin scale. CT images were evaluated to determine the Evans’ index and to enumerate the number of arachnoid granulations. Association between the clinical characteristics with ventriculoperitoneal shunt insertion and the 3-month modified Rankin scale were assessed.ResultsThe initial Evans’ index was positively associated with mFisher grade and age, but not the number of arachnoid granulations. 16.4 % patients required insertion of a ventriculoperitoneal shunt. The number of arachnoid granulations were a significant negative predictor of ventriculoperitoneal shunt insertion [OR: 0.251 (95% CI:0.073-0.862; P=0.028)]. There was significant difference in the number of arachnoid granulations between those with and without ventriculoperitoneal shunt (p=0.002). No patient with greater than 4 arachnoid granulations required a ventriculoperitoneal shunt, irrespective of severity of initial grade.ConclusionArachnoid granulations may be protective against the development of shunt dependent chronic hydrocephalus after aneurysmal subarachnoid hemorrhage. This is irrespective of presenting hemorrhage severity. This is a potentially novel radiologic biomarker and anatomic predictor of shunt dependence.
Biological Aging of CNS-Resident Cells Alters the Clinical Course and Immunopathology of Autoimmune Demyelinating Disease
Authors: Atkinson Jeffrey R. , Jerome Andrew D. , Sas Andrew R. , Munie Ashley , Wang Cankun , Ma Anjun , Arnold W. David , Segal Benjamin M. 
Published: December 2021

AbstractBiological aging is the strongest factor associated with the clinical phenotype of multiple sclerosis (MS). Relapsing remitting MS (RRMS) typically presents in the third or fourth decade, while the mean age of presentation of progressive MS (pMS) is 45 years old. Here we show that experimental autoimmune encephalomyelitis (EAE), induced by the adoptive transfer of encephalitogenic CD4+Th17 cells, is more severe, and less like to remit, in middle-aged compared with young adult mice. Donor T cells and neutrophils are more abundant, while B cells are relatively sparse, in central nervous system (CNS) infiltrates of the older mice. Experiments with reciprocal bone marrow chimeras demonstrate that radio-resistant, non-hematopoietic cells play a dominant role in shaping age-dependent features of the neuroinflammatory response, as well as the clinical course, during EAE. Reminiscent of pMS, EAE in middle-aged adoptive transfer recipients is characterized by widespread microglial activation. Microglia from older mice express a distinctive transcriptomic profile, suggestive of enhanced chemokine synthesis and antigen presentation. Collectively, our findings suggest that drugs that suppress microglial activation, and acquisition or expression of aging-associated properties, may be beneficial in the treatment of progressive forms of inflammatory demyelinating disease.
A New Paradigm for Investigating Real-World Social Behavior and its Neural Underpinnings
Authors: Alreja Arish , Ward Michael J. , Ma Qianli , Russ Brian E. , Bickel Stephan , Van Wouwe Nelleke C. , González-Martínez Jorge A. , Neimat Joseph S. , Abel Taylor J. , Bagić Anto , Parker Lisa S. , Richardson R. Mark , Schroeder Charles E. , Morency Louis–Philippe , Ghuman Avniel Singh 
Published: December 2021

AbstractEye tracking and other behavioral measurements collected from patient-participants in their hospital rooms afford a unique opportunity to study immersive natural behavior for basic and clinical translational research. We describe an immersive social and behavioral paradigm implemented in patients undergoing evaluation for surgical treatment of epilepsy, with electrodes implanted in the brain to determine the source of their seizures. Our studies entail collecting eye tracking with other behavioral and psychophysiological measurements from patient-participants during unscripted behavior, including social interactions with clinical staff, friends and family, in the hospital room. This approach affords a unique opportunity to study the neurobiology of natural social behavior, though it requires carefully addressing distinct logistical, technical, and ethical challenges. Collecting neurophysiological data synchronized to behavioral and psychophysiological measures helps us to study the relationship between behavior and physiology. Combining across these rich data sources while participants eat, read, converse with friends and family, etc., enables clinical-translational research aimed at understanding the participants’ disorders and clinician-patient interactions, as well as basic research into natural, real-world behavior. We discuss data acquisition, quality control, annotation, and analysis pipelines that are required for our studies. We also discuss the clinical, logistical, and ethical and privacy considerations critical to working in the hospital setting.
Super-immunity by broadly protective nanobodies to sarbecoviruses
Authors: Xiang Yufei , Huang Wei , Liu Hejun , Sang Zhe , Nambulli Sham , Tubiana Jérôme , Williams Kevin L , Duprex W Paul , Schneidman-Duhovny Dina , Wilson Ian A. , Taylor Derek J. , Shi Yi 
Published: December 2021

AbstractVaccine boosters and infection can facilitate the development of SARS-CoV-2 antibodies with improved potency and breadth. Here, we observed super-immunity in a camelid extensively immunized with the SARS-CoV-2 receptor-binding domain (RBD). We rapidly isolated a large repertoire of specific ultrahigh-affinity nanobodies that bind strongly to all known sarbecovirus clades using integrative proteomics. These pan-sarbecovirus nanobodies (psNbs) are highly effective against SARS-CoV and SARS-CoV-2 variants including the Omicron, with the best median neutralization potency at single-digit ng/ml. Structural determinations of 13 psNbs with the SARS-CoV-2 spike or RBD revealed five epitope classes, providing insights into the mechanisms and evolution of their broad activities. The highly evolved psNbs target small, flat, and flexible epitopes that contain over 75% of conserved RBD surface residues. Their potencies are strongly and negatively correlated with the distance of the epitopes to the receptor binding sites. A highly potent, inhalable and bispecific psNb (PiN-31) was developed. Our findings inform on the development of broadly protective vaccines and therapeutics.One sentence summarySuccessive immunization of SARS-CoV-2 RBD in a camelid enhanced the development of super-immunity and isolation and systematic characterization of a large repertoire of ultrahigh-affinity pan-sarbecovirus single-chain VHH antibodies to understand the evolution of this potent and broad immune response.
Stronger density-dependent growth of Japanese sardine with lower food availability: Comparison of growth and zooplankton biomass between a historical and current stock-increase period in the western North Pacific
Authors: Kamimura Yasuhiro , Tadokoro Kazuaki , Furuichi Sho , Yukami Ryuji 
Published: December 2021

AbstractDensity dependence is a fundamental concept for fish population dynamics. Although density-dependent growth and maturity among older juveniles and adults is important for regulating fish population size and for fisheries management, the mechanism of density dependence for marine fishes remains unclear. Here, we examined changes in Japanese sardine growth with increasing abundance beginning in the 2010s and how the current pattern of density-dependent growth differs from that of a previous stock-increase period from the 1970s to early 1980s. During the current period of increasing abundance, mean standard length has already dropped to the lowest level yet observed and growth has declined more sharply with increased abundance than in the 1970s and 1980s. Mesozooplankton biomass in July in the summer feeding grounds was also lower during the current period. Therefore, our results suggest that summer food availability in the western North Pacific controls the strength of density-dependent growth. A lower carrying capacity for Japanese sardine could account for the stronger density dependence of growth observed in the 2010s; this indicates that future Japanese sardine abundance might not increase as much as in the 1980s unless food availability improves.
DeepMHCII: A Novel Binding Core-Aware Deep Interaction Model for Accurate MHC II-peptide Binding Affinity Prediction
Authors: You Ronghui , Qu Wei , Mamitsuka Hiroshi , Zhu Shanfeng 
Published: December 2021

AbstractComputationally predicting MHC-peptide binding affinity is an important problem in immunological bioinformatics. Recent cutting-edge deep learning-based methods for this problem are unable to achieve satisfactory performance for MHC class II molecules. This is because such methods generate the input by simply concatenating the two given sequences: (the estimated binding core of) a peptide and (the pseudo sequence of) an MHC class II molecule, ignoring the biological knowledge behind the interactions of the two molecules. We thus propose a binding core-aware deep learning-based model, DeepMHCII, with binding interaction convolution layer (BICL), which allows integrating all potential binding cores (in a given peptide) and the MHC pseudo (binding) sequence, through modeling the interaction with multiple convolutional kernels. Extensive empirical experiments with four large-scale datasets demonstrate that DeepMHCII significantly outperformed four state-of-the-art methods under numerous settings, such as five-fold cross-validation, leave one molecule out, validation with independent testing sets, and binding core prediction. All these results with visualization of the predicted binding cores indicate the effectiveness and importance of properly modeling biological facts in deep learning for high performance and knowledge discovery. DeepMHCII is publicly available at https://weilab.sjtu.edu.cn/DeepMHCII/.
Cryo-EM structures and binding of mouse and human ACE2 to SARS-CoV-2 variants of concern indicate that mutations enabling immune escape could expand host range
Authors: Ni Dongchun , Turelli Priscilla , Beckert Bertrand , Nazarov Sergey , Uchikawa Emiko , Myasnikov Alexander , Pojer Florence , Trono Didier , Stahlberg Henning , Lau Kelvin 
Published: December 2021

ABSTRACTInvestigation of potential hosts of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is crucial to understanding future risks of spillover and spillback. SARS-CoV-2 has been reported to be transmitted from humans to various animals after requiring relatively few mutations.[1] There is significant interest in describing how the virus interacts with mice as they are well adapted to human environments, are used widely as infection models and can be infected.[2] Structural and binding data of the mouse ACE2 receptor with the Spike protein of newly identified SARS-CoV-2 variants are needed to better understand the impact of immune system evading mutations present in variants of concern (VOC). Previous studies have developed mouse-adapted variants and identified residues critical for binding to heterologous ACE2 receptors.[3,4] Here we report the cryo-EM structures of mouse ACE2 bound to trimeric Spike ectodomains of four different VOC: Beta, Omicron BA.1, Omicron BA.2.12.1 and Omicron BA.4/5. These variants represent the oldest to the newest variants known to bind the mouse ACE2 receptor. Our high-resolution structural data complemented with bio-layer interferometry (BLI) binding assays reveal a requirement for a combination of mutations in the Spike protein that enable binding to the mouse ACE2 receptor.AUTHOR SUMMARYThe SARS-CoV-2 virus can infect different types of animals beyond humans. The virus uses its Spike protein on its surface to bind to cells. These cells have a protein called ACE2 that the Spike protein recognizes. Animals have slightly different ACE2 receptors compared to humans. Mice are widely used as a research animal and live in the same environments as humans so scientists are particularly interested. Understanding how Spike proteins binds to the mouse ACE2 receptor allows us to understand the impact of immune evading mutations found in new variants. We use a high resolution imaging technique called cryo-electron microscopy to look at how different Spike variants bind to the ACE2 receptor from mouse at a resolution where we can see the amino acids. We can see directly the individual amino acids and mutations on the Spike protein that interact with the mouse ACE2 receptor. Many of the mutations found in variants of concern also increase the strength of binding to the mouse ACE2 receptor. This result suggests that mutations in the Spike protein of future variants may have an additional effect in influencing how it binds to not only human ACE2 receptors but to mice and also different animals.