bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development and Initial Validation of the Duke Misophonia Questionnaire
Authors: Rosenthal M. Zachary , Anand Deepika , Robbins Clair , Williams Zachary J. , Guetta Rachel , Trumbull Jacqueline , Kelly Lisalynn 
Published: May 2021

AbstractMisophonia is characterized by decreased tolerance and accompanying defensive motivational system responding to certain aversive sounds and contextual cues associated with such stimuli, typically repetitive oral (e.g., eating sounds) or nasal (e.g., breathing sounds) stimuli. Responses elicit significant psychological distress and impairment in functioning, and include acute increases in (a) negative affect (e.g., anger, anxiety, and disgust), (b) physiological arousal (e.g., sympathetic nervous system activation), and (c) overt behavior (e.g., escape behavior and verbal aggression toward individuals generating triggers). A major barrier to research and treatment of misophonia is the lack of rigorously validated assessment measures. As such, the primary purpose of this study was to develop and psychometrically validate a self-report measure of misophonia, the Duke Misophonia Questionnaire (DMQ). There were two phases of measure development. In Phase 1, items were generated and iteratively refined from a combination of the scientific literature and qualitative feedback from misophonia sufferers, their family members, and professional experts. In Phase 2, a large community sample of adults (n = 424) completed DMQ candidate items and other measures needed for psychometric analyses. A series of iterative analytic procedures (e.g., factor analyses and IRT) were used to derive final DMQ items and scales. The final DMQ is 86 items, and includes subscales: (1) Trigger frequency (16 items), (2) Affective Responses (5 items), (3) Physiological Responses (8 items), (4) Cognitive Responses (10 items), (5) Coping Before (6 items), (6) Coping During (10 items), (7) Coping After (5 items), (8) Impairment (12 items), and Beliefs (14 items). Composite scales were derived for overall Symptom Severity (combined Affective, Physiological, and Cognitive subscales) and Coping (combined the three Coping subscales). The analytic procedures used enable administration of the total DMQ, individual subscales, or the derived composite scales.
Following the Trail of One Million Genomes: Footprints of SARS-CoV-2 Adaptation to Humans
Authors: Akther Saymon , Bezrucenkovas Edgaras , Li Li , Sulkow Brian , Di Lia , Pante Desiree , Martin Che L. , Luft Benjamin J. , Qiu Weigang 
Published: May 2021

AbstractSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has accumulated genomic mutations at an approximately linear rate since it first infected human populations in late 2019. Controversies remain regarding the identity, proportion, and effects of adaptive mutations as SARS-CoV-2 evolves from a bat-to a human-adapted virus. The potential for vaccine-escape mutations poses additional challenges in pandemic control. Despite being of great interest to therapeutic and vaccine development, human-adaptive mutations in SARS-CoV-2 are masked by a genome-wide linkage disequilibrium under which neutral and even deleterious mutations can reach fixation by chance or through hitchhiking. Furthermore, genome-wide linkage equilibrium imposes clonal interference by which multiple adaptive mutations compete against one another. Informed by insights from microbial experimental evolution, we analyzed close to one million SARS-CoV-2 genomes sequenced during the first year of the COVID-19 pandemic and identified putative human-adaptive mutations according to the rates of synonymous and missense mutations, temporal linkage, and mutation recurrence. Furthermore, we developed a forward-evolution simulator with the realistic SARS-CoV-2 genome structure and base substitution probabilities able to predict viral genome diversity under neutral, background selection, and adaptive evolutionary models. We conclude that adaptive mutations have emerged early, rapidly, and constantly to dominate SARS-CoV-2 populations despite clonal interference and purifying selection. Our analysis underscores a need for genomic surveillance of mutation trajectories at the local level for early detection of adaptive and immune-escape variants. Putative human-adaptive mutations are over-represented in viral proteins interfering host immunity and binding host-cell receptors and thus may serve as priority targets for designing therapeutics and vaccines against human-adapted forms of SARS-CoV-2.
Multimodal Analysis Reveals Differential Immuno-Metabolic Features in Lung Squamous Cell Carcinoma and Adenocarcinoma
Authors: Leitner Brooks P. , Ospanova Shyryn , Beisenbayeva Aray , Givechian Kevin B. , Politi Katerina , Perry Rachel J. 
Published: May 2021

AbstractBackgroundThe relationship between systemic metabolism, immune function, and lung cancer is complex and remains poorly defined. Seemingly paradoxically, overweight and obesity confer an improved response to immune checkpoint inhibition in non-small cell lung cancer (NSCLC); however, it is not known whether excess body weight or adiposity impacts the immunometabolic tumor microenvironment.MethodsUtilizing three complementary National Cancer Institute-funded open-source databases containing 18F-fluorodeoxyglucose positron-emission tomography/computed tomography (PET-CT) images for tumor and tissue glucose uptake, adipose tissue and skeletal muscle mass, histology annotated with tumor infiltrating leukocytes, and tumor RNA sequencing, we performed a retrospective cross-sectional analysis to examine phenotypic, metabolic, and genomic intersections of adiposity and tumor immune-metabolism in patients with lung adenocarcinoma (LUAD) versus squamous cell carcinoma (LUSC).ResultsOur data reveal distinct immunometabolomic features of LUSC as compared to LUAD: visceral fat content was negatively correlated with both tumor glucose uptake and leukocyte infiltration. Subcutaneous and visceral adiposity conferred different effects on the tumor genetic landscapes in both tumor types. LUSC tumors showed greater gene expression pathways related to pyruvate, glucose, amino acid, and lipid metabolism, in addition to significantly greater 18F-FDG uptake compared with LUAD, suggesting deeper metabolic regulation within the LUSC tumor microenvironment.ConclusionsSeveral immunometabolomic characteristics of LUSC and LUAD differ, including tumor glucose uptake and the associated metabolic pathways in the tumor, as well as the impact of visceral adiposity on tumor metabolism. These data may highlight opportunities to advance mechanistically targeted precision medicine approaches by better understanding the interplay between metabolic, immunologic, and genomic factors in lung cancer treatment.
Severity assessment of single dose Oxford–AstraZeneca vaccinated individuals infected with SARS CoV-2 in the Southeast Bangladesh
Authors: Rana Eaftekhar Ahmed , Dutta Pronesh , Islam Md. Sirazul , Nizami Tanvir Ahmad , Das Tridip , Chowdhury Sharmin , Das Goutam Buddha 
Published: May 2021

AbstractThe present global endeavor to uncover the most effective vaccines against severe acute respiratory syndrome coronavirus (SARS-CoV-2) that can tremendously prevent transmission, infection and significantly reduce public health risk. COVID-19 vaccination program is underway in different parts of the world including Bangladesh but till to date there is no available health data revealed among the vaccinated peoples. We conducted a cross-sectional study from February 15 to April 15, 2021 to assess the health status of 1st dose Oxford-AstraZeneca vaccinated individuals infected with SARS CoV-2. Standard virological method, real-time reverse transcriptase-polymerase chain reaction (RT-qPCR) was performed to detect SARS-CoV-2 and the different health parameters from vaccinated individuals were collected through direct mobile phone contact using pre-structured questionnaires. A total of 6146 suspected samples were tested and 1752 were found positive for SARS-CoV-2, of them 200 individuals were identified who received 1st dose of COVID-19 vaccine. Within the test period, majority of male (65.6%) and female (34.4%) carried moderate numbers of viruses which comprise between 30.01-35 cyclic threshold (ct) values. Among the vaccinated individuals, 165 (82.5%; 95% CI: 76.51 - 87.5) persons were not hospitalized and 177 (88.5%; 95% CI: 83.24 - 92.57) did not show any respiratory difficulties. Only a few (16) (8%; 95% CI: 4.64 - 12.67) of COVID-19 positive patients needed extra oxygen support and 199 (99.5%; 95% CI: 97.25 - 99.99) individuals didn’t require any intensive care unit (ICU) interference. Overall, oxygen saturation was recorded around 96.8% and respiratory difficulties did not extend more than 5 days, irrespective of age and sex during the infection period. Within the vaccinated COVID-19 positive individuals 113 (56.5%; 95% CI: 49.33 - 63.48) and 111(55.5%; 95% CI: 48.32 - 62.51) persons have normal physiological taste and smell. However, we have found a larger proportion of vaccinated persons (129) (64.5%; 95% CI: 57.44 - 71.12) carrying different comorbidity, among them high blood pressure 36 (27.9%; 95% CI, 20.37 - 36.48) and diabetes 32 (24.8%; 95% CI: 17.63 - 33.18) were found more prevalent. Moreover, the significant finding of the present study was 199 (99.5%; 95% CI: 97.25 - 99.99) vaccinated individuals survived with good health conditions and became negative in RT-qPCR. The authors suggest that health risk assessment among the COVID-19 vaccinated persons when infected with SARS-CoV-2 is crucial and time demanding task for the whole world. However, the present study illustrates that the administration of the 1st dose Oxford-AstraZeneca vaccine significantly reduces health risk during the COVID-19 infection period.
In-solution buffer-free digestion for the analysis of SARS-CoV-2 RBD proteins allows a full sequence coverage and detection of post-translational modifications in a single ESI-MS spectrum
Authors: Espinosa Luis Ariel , Ramos Yassel , Andújar Ivan , Torres Enso Onill , Cabrera Gleysin , Martín Alejandro , González Diamilé , Chinea Glay , Becquet Mónica , González Isabel , Canaán-Haden Camila , Nelson Elías , Rojas Gertrudis , Pérez-Massón Beatriz , Pérez-Martínez Dayana , Boggiano Tamy , Palacio Julio , Lozada-Chang Sum Lai , Hernández Lourdes , de la Luz Hernández Kathya Rashida , Markku Saloheimo , Marika Vitikainen , Valdés-Balbín Yury , Santana-Medero Darielys , Rivera Daniel G. , Vérez-Bencomo Vicente , Emalfarb Mark , Tchelet Ronen , Guillén Gerardo , Limonta Miladys , Pimentel Eulogio , Ayala Marta , Besada Vladimir , González Luis Javier 
Published: May 2021

AbstractSubunit vaccines based on the receptor-binding domain (RBD) of the spike protein of SARS-CoV-2, are among the most promising strategies to fight the COVID-19 pandemic. The detailed characterization of the protein primary structure by mass spectrometry (MS) is mandatory, as described in ICHQ6B guidelines. In this work, several recombinant RBD proteins produced in five expression systems were characterized using a non-conventional protocol known as in-solution buffer-free digestion (BFD). In a single ESI-MS spectrum, BFD allowed very high sequence coverage (≥ 99 %) and the detection of highly hydrophilic regions, including very short and hydrophilic peptides (2-8 amino acids), the His6-tagged C-terminal peptide carrying several post-translational modifications at Cys538such as cysteinylation, glutathionylation, cyanilation, among others. The analysis using the conventional digestion protocol allowed lower sequence coverage (80-90 %) and did not detect peptides carrying some of the above-mentioned post-translational modifications. The two C-terminal peptides of a dimer [RBD(319-541)-(His)6]2linked by an intermolecular disulfide bond (Cys538-Cys538) with twelve histidine residues were only detected by BFD. This protocol allows the detection of the four disulfide bonds present in the native RBD and the low-abundance scrambling variants, free cysteine residues, O-glycoforms and incomplete processing of the N-terminal end, if present. Artifacts that might be generated by the in-solution BFD protocol were also characterized. BFD can be easily implemented and we foresee that it can be also helpful to the characterization of mutated RBD.
Sexual selection and sexual size dimorphism in animals
Authors: Janicke Tim , Fromonteil Salomé 
Published: May 2021

AbstractSexual selection is often considered as a critical evolutionary force promoting sexual size dimorphism (SSD) in animals. However, empirical evidence for a positive relationship between sexual selection on males and male-biased SSD received mixed support depending on the studied taxonomic group and on the method used to quantify sexual selection. Here, we present a meta-analytic approach accounting for phylogenetic non-independence to test how standardized metrics of the opportunity and strength of pre-copulatory sexual selection relate to SSD across a broad range of animal taxa comprising up to 102 effect sizes from 64 species. We found that SSD was correlated with the sex difference in the opportunity for sexual selection but not with the sex difference in the Bateman gradient. These findings suggest that pre-copulatory sexual selection plays a limited role for the evolution of sexual size dimorphism in a broad phylogenetic context.
Bisphenol A derivatives act as novel coactivator binding inhibitors for estrogen receptor β
Authors: Iwamoto Masaki , Masuya Takahiro , Hosose Mari , Tagawa Koki , Ishibashi Tomoka , Yoshihara Eiji , Downes Michael , Evans Ronald M. , Matsushima Ayami 
Published: May 2021

AbstractBisphenol A and its derivatives are recognized endocrine disruptors based on their complex effects on estrogen receptor (ER) signaling. While the effects of bisphenol derivatives on ERα have been thoroughly evaluated, how these chemicals affect ERβ signaling is not well understood. Herein, we identified novel ERβ ligands by screening a chemical library of bisphenol derivatives. Many of the compounds identified showed intriguing dual activities as ERα agonists and ERβ antagonists. Docking simulations suggested that these compounds act as coactivator binding inhibitors (CBIs). Direct binding experiments using wild-type and mutated ERβ demonstrated the presence of a second ligand interaction position at the coactivator binding site in ERβ. Our study is the first to propose that bisphenol derivatives act as CBIs, presenting a critical view point for future ER signaling-based drug development.
SARS-COV-2 Recombinant Receptor-Binding-Domain (RBD) Induces Neutralising Antibodies Against Variant Strains of SARS-CoV-2 and SARS-CoV-1
Authors: John Law Lok Man , Logan Michael , Joyce Michael , Landi Abdolamir , Hockman Darren , Crawford Kevin , Johnson Janelle , LaChance Gerald , Saffran Holly , Shields Justin , Hobart Eve , Brassard Raelynn , Arutyunova Elena , Pabbaraju Kanti , Croxen Matthew , Tipples Graham , Lemieux M Joanne , Tyrrell Lorne , Houghton Michael 
Published: May 2021

AbstractSARS-CoV-2 is the etiological agent of COVID19. There are currently several licensed vaccines approved for human use and most of them are targeting the spike protein (or virion) in the virion envelope to induce protective immunity. Recently, variants that spread more quickly have emerged. There is evidence that some of these variants are less sensitive to neutralizationin vitro, but it is not clear whether they can evade vaccine induced protection. In this study, we tested the utility of SARS-CoV-2 spike RBD as a vaccine antigen and explore the effect of formulation with Alum/MPLA or AddaS03 adjuvants. Our results indicate RBD induces high titers of neutralizing antibodies and activates strong cellular immune responses. There is also significant cross-neutralisation of variants B1.1.7 and B.1.351 and to a lesser extent, SARS-CoV-1. These results indicate that recombinant RBD can be a viable candidate as a stand-alone vaccine or as a booster shot to diversify our strategy for COVID19 protection.
The Fluorescent Dye 1,6-Diphenyl-1,3,5-Hexatriene Binds to Amyloid Fibrils Formed by Human Amylin and Provides a New Probe of Amylin Amyloid Kinetics
Authors: Li Ming-Hao , Manathunga Lakshan , London Erwin , Raleigh Daniel P. 
Published: May 2021

AbstractThe fluorescent dye 1,6-diphenyl-1,3,5-hexatriene (DPH) is widely used as a probe of membrane order. We show that DPH also interacts with amyloid fibrils formed by human amylin (also known as islet amyloid polypeptide) in solution and this results in a 100-fold increase in DPH fluorescence for a sample of 20μM human amylin and 0.25 μM DPH. No increase in DPH fluorescence is observed with the non-amyloidogenic rat amylin or with freshly dissolved, non-fibrillar human amylin. The time course of amyloid formation by amylin was followed by monitoring the fluorescence of added DPH as a function of time and was similar to that monitored by the standard fluorescent probe thioflavin-T. The inclusion of DPH in the buffer did not perturb the time course of amyloid formation under the conditions examined and the time course was independent of the range of DPH concentrations tested (0.25 to 5 μM). Maximum final fluorescence intensity is observed at substoichiometric ratios of DPH to amylin. No significant increase in fluorescence was observed during the lag phase of amyloid formation, and the implications for the structure of amylin pre-fibril oligomers are discussed. Human amylin contains three aromatic residues. A triple aromatic to leucine mutant forms amyloid and DPH binds to the resulting fibrils, indicating that interactions with aromatic side chains are not required for DPH amylin amyloid interactions. DPH may be especially useful for studies on mutant amylins and other polypeptides in which changes in charged residues might complicate interpretation of thioflavin-T fluorescence.
ScreenGarden: A shinyR application for fast and easy analysis of plate-based high-throughput screens
Authors: Klemm Cinzia , Howell Rowan M. S. , Thorpe Peter H. 
Published: May 2021

AbstractColony growth on solid media is a simple and effective measure for high-throughput genomic experiments such as yeast-two hybrid, Synthetic Genetic Arrays and Synthetic Physical Interaction screens. The development of robotic pinning tools has facilitated the experimental design of these assays, and different imaging software can be used to automatically measure colony sizes on plates. However, comparison to control plates and statistical data analysis is often laborious and pinning issues or plate specific growth effects can lead to the detection of false positive growth defects. We have developed ScreenGarden, a shinyR application, to enable easy, quick and robust data analysis of plate-based high throughput assays.
Decentralized Brain Age Estimation using MRI Data
Authors: Basodi Sunitha , Raja Rajikha , Ray Bhaskar , Gazula Harshvardhan , Liu Jingyu , Verner Eric , Calhoun Vince D. 
Published: May 2021

AbstractRecent studies have demonstrated that neuroimaging data can be used to predict brain age, as it captures information about the neuroanatomical and functional changes the brain undergoes during development and the aging process. However, researchers often have limited access to neuroimaging data because of its challenging and expensive acquisition process, thereby limiting the effectiveness of the predictive model. Decentralized models provide a way to build more accurate and generalizable prediction models, bypassing the traditional data-sharing methodology. In this work, we propose a decentralized method for brain age estimation and evaluate it on three different feature sets, including both volumetric and voxelwise structural MRI data as well as resting functional MRI data. The results demonstrate that a decentralized brain age model can achieve similar performance compared to the models trained with all the data in one location.
Characterization of the gene repertoire and environmentally driven expression patterns in Tanner crab (Chionoecetes bairdi)
Authors: Crandall Grace , Jensen Pamela C. , White Samuel J. , Roberts Steven 
Published: May 2021

AbstractTanner crab (Chionoecetes bairdi) are an economically important species that is threatened by ocean warming and Bitter Crab Disease, which is caused by an endoparasitic dinoflagellate,Hematodinium. Little is known about disease transmission or its link to host mortality, or how ocean warming will affect pathogenicity or host susceptibility. To provide a transcriptomic resource for the Tanner crab, we generated a suite of RNA-seq libraries encompassing pooled hemolymph samples from crab displaying differing infection statuses and maintained at different temperatures (ambient (7.5°C), elevated (10°C), or decreased (4°C)). After assembling a transcriptome and performing a multifactor differential gene expression analysis, we found genes influenced by temperature in relation to infection, and detected some of those genes over time at the individual level using RNAseq data from one crab. Biological processes associated with those genes include lipid storage, transcription, response to oxidative stress, cell adhesion, and morphogenesis. Alteration in lipid storage and transcription provide insight into how temperature impacts energy allocation inHematodiniuminfected crabs. Alteration in expression patterns in genes associated with morphogenesis could suggest hemocytes were changing morphology and/or type in response to temperature. This project provides insight into howHematodiniuminfection could influence crab physiology as oceans warm.
An improved fluorescent noncanonical amino acid for measuring conformational distributions using time-resolved transition metal ion FRET
Authors: Zagotta William N. , Sim Brandon S. , Nhim Anthony K. , Raza Marium M. , Evans Eric G.B. , Venkatesh Yarra , Jones Chloe M. , Mehl Ryan A. , Petersson E. James , Gordon Sharona E. 
Published: May 2021

AbstractWith the recent explosion in high-resolution protein structures, one of the next frontiers in biology is elucidating the mechanisms by which conformational rearrangements in proteins are regulated to meet the needs of cells under changing conditions. Rigorously measuring protein energetics and dynamics requires the development of new methods that can resolve structural heterogeneity and conformational distributions. We have previously developed steady-state transition metal ion fluorescence resonance energy transfer (tmFRET) approaches using a fluorescent noncanonical amino acid donor (Anap) and transition metal ion acceptor, to probe conformational rearrangements in soluble and membrane proteins. Here, we show that the fluorescent noncanonical amino acid Acd has superior photophysical properties that extend its utility as a donor for tmFRET. Using maltose binding protein (MBP) expressed in mammalian cells as a model system, we show that Acd is comparable to Anap in steady-state tmFRET experiments and that its long, single-exponential lifetime is better suited for probing conformational distributions using time-resolved FRET. These experiments reveal differences in heterogeneity in the apo and holo conformational states of MBP and produce accurate quantification of the distributions among apo and holo conformational states at subsaturating maltose concentrations. Our new approach using Acd for time-resolved tmFRET sets the stage for measuring the energetics of conformational rearrangements in soluble and membrane proteins in near-native conditions.