bluuebunny/crossref_metadata_2025_split huggingface dataset:
Epidermoid Cyst of the Floor of the Mouth
Authors: Erol Behçet , Laçin Nihat 
Published: January 2022

Abstract:
Epidermoid cysts are rare, slow-growing, benign, developmental cysts that are derived from abnormally situated ectodermal tissue. Epidermoid cysts may grow anywhere on the body and about 7% of them are located in the head and neck region. They are usually asymptomatic over years but can be symptomatic due to secondary changes or the growing size. Clinically, the lesion presents as a slow-growing asymptomatic mass, usually located in the midline, above or below the mylohyoid muscle. Surgical excision from the floor of the mouth is indicated to relieve symptoms and prevent possible infection. This swelling on the floor of the mouth can sometimes cause serious problems with difficulty for swallowing and speaking. The purpose of this report is to present a case of sublingual epidermoid cyst of the floor of the mouth.
Integrated Autolysis, DNA Hydrolysis and Precipitation Enables an Improved Bioprocess for Q-Griffithsin, a Broad-Spectrum Antiviral and Clinical-Stage anti-COVID-19 Candidate
Authors: Decker John S. , Menacho-Melgar Romel , Lynch Michael D. 
Published: January 2022

AbstractAcross the biomanufacturing industry, innovations are needed to improve efficiency and flexibility, especially in the face of challenges such as the COVID-19 pandemic. Here we report an improved bioprocess for Q-Griffithsin, a broad-spectrum antiviral currently in clinical trials for COVID-19. Q-Griffithsin is produced at high titer inE. coliand purified to anticipated clinical grade without conventional chromatography or the need for any fixed downstream equipment. The process is thus both low-cost and highly flexible, facilitating low sales prices and agile modifications of production capacity, two key features for pandemic response. The simplicity of this process is enabled by a novel unit operation that integrates cellular autolysis, autohydrolysis of nucleic acids, and contaminant precipitation, giving essentially complete removal of host cell DNA as well as reducing host cell proteins and endotoxin by 3.6 and 2.4 log10units, respectively. This unit operation can be performed rapidly and in the fermentation vessel, such that Q-GRFT is obtained with 100% yield and >99.9% purity immediately after fermentation and requires only a flow-through membrane chromatography step for further contaminant removal. Using this operation or variations of it may enable improved bioprocesses for a range of other high-value proteins inE. coli.HighlightsIntegrating autolysis, DNA hydrolysis and precipitation enables process simplificationAutolysis reduces endotoxin release and burden to purificationQ-Griffithsin recovered from fermentation vessel at >99.9% purity and 100% yieldQ-Griffithsin purified to anticipated clinical grade without conventional chromatographyThe resulting bioprocess is 100% disposables-compatible, scalable, and low-cost
Nonself Mutations in the Spike Protein Suggest an Increase in the Antigenicity and a Decrease in the Virulence of the Omicron Variant of SARS-CoV-2
Authors: Otaki Joji M. , Nakasone Wataru , Nakamura Morikazu 
Published: January 2022

AbstractDespite extensive worldwide vaccination, the current COVID-19 pandemic caused by SARS-CoV-2 continues. The Omicron variant is a recently emerged variant of concern and is now taking over the Delta variant. To characterize the potential antigenicity of the Omicron variant, we examined the distributions of SARS-CoV-2 nonself mutations (in reference to the human proteome) as 5 amino acid stretches of short constituent sequences (SCSs) in the Omicron and Delta proteomes. The number of nonself SCSs did not differ much throughout the Omicron, Delta, and Reference Sequence (RefSeq) proteomes but markedly increased in the receptor binding domain (RBD) of the Omicron spike protein compared to those of the Delta and RefSeq proteins. In contrast, the number of nonself SCSs decreased in non-RBD regions in the Omicron spike protein, compensating for the increase in the RBD. Several nonself SCSs were tandemly present in the RBD of the Omicron spike protein, likely as a result of selection for higher binding affinity to the ACE2 receptor (and hence higher infectivity and transmissibility) at the expense of increased antigenicity. Taken together, the present results suggest that the Omicron variant has evolved to have higher antigenicity and less virulence in humans despite increased infectivity and transmissibility.
Schild analysis of the interaction between parthenolide and cocaine suggests an allosteric relationship for their effects on planarian motility
Authors: Kakuturu Jyothi , O’Brien Mary , Pagán Oné R. 
Published: January 2022

AbstractThe freshwater planarian is an emerging animal model in neuropharmacology due to its close parallels with the nervous system of vertebrates. Cocaine is a naturally occurring compound and an abused drug, as well as the ‘founding member’ of the local anesthetic family. Sesquiterpene lactones of the parthenolide class are naturally occurring products that act as behavioral and physiological antagonists of cocaine in planarians and rats, respectively. One of the best-characterized planarian behaviors induced by various compounds is the change in locomotor velocity. Previous work from our laboratory showed that both parthenolide and cocaine reduced planarian motility and that parthenolide reversed the cocaine-induced motility decrease at concentrations where parthenolide does not affect the movement of the worms. However, the exact mechanism of the cocaine/parthenolide antagonism is unknown. Here, we report the results of a Schild analysis to explore the parthenolide/cocaine relationship in the planarian Girardia tigrina. The Schild slopes of the Δ parthenolide ± cocaine and Δ cocaine ± parthenolide were -0.33 and -0.43, respectively. These slopes were not statistically different from each other, and both were statistically different from -1, suggesting an allosteric relationship between these two compounds. To the best of our knowledge, this is the first study aimed at studying the mechanism of action of the antagonism between cocaine and parthenolide.
Increasing adult density compromises anti-bacterial defense in Drosophila melanogaster
Authors: Das Paresh Nath , Basu Aabeer , Prasad Nagaraj Guru 
Published: January 2022

AbstractThe density-dependent prophylaxis hypothesis predicts that risk of pathogen transmission increases with increase in population density, and in response to this, organisms mount a prophylactic immune response when exposed to high density. This prophylactic response is expected to help organisms improve their chances of survival when exposed to pathogens. Alternatively, organisms living at high densities can exhibit compromised defense against pathogens due to lack of resources and density associated physiological stress; the density stress hypothesis. We housed adult Drosophila melanogaster flies at different densities and measured the effect this has on their post-infection survival and resistance to starvation. We find that flies housed at higher densities show greater mortality after being infected with bacterial pathogens, while also exhibiting increased resistance to starvation. Our results are more in line with the density-stress hypothesis that postulates a compromised immune system when hosts are subjected to high densities.
Mapping the antigenic diversification of SARS-CoV-2
Authors: van der Straten Karlijn , Guerra Denise , van Gils Marit J. , Bontjer Ilja , Caniels Tom G. , van Willigen Hugo D.G. , Wynberg Elke , Poniman Meliawati , Burger Judith A. , Bouhuijs Joey H. , van Rijswijk Jacqueline , Olijhoek Wouter , Liesdek Marinus H. , Lavell A. H. Ayesha , Appelman Brent , Sikkens Jonne J. , Bomers Marije K. , Han Alvin X. , Nichols Brooke E. , Prins Maria , Vennema Harry , Reusken Chantal , de Jong Menno D. , de Bree Godelieve J. , Russell Colin A. , Eggink Dirk , Sanders Rogier W. 
Published: January 2022

SummaryLarge-scale vaccination campaigns have prevented countless hospitalizations and deaths due to COVID-19. However, the emergence of SARS-CoV-2 variants that escape from immunity challenges the effectiveness of current vaccines. Given this continuing evolution, an important question is when and how to update SARS-CoV-2 vaccines to antigenically match circulating variants, similar to seasonal influenza viruses where antigenic drift necessitates periodic vaccine updates. Here, we studied SARS-CoV-2 antigenic drift by assessing neutralizing activity against variants-of-concern (VOCs) of a unique set of sera from patients infected with a range of VOCs. Infections with D614G or Alpha strains induced the broadest immunity, while individuals infected with other VOCs had more strain-specific responses. Omicron BA.1 and BA.2 were substantially resistant to neutralization by sera elicited by all other variants. Antigenic cartography revealed that Omicron BA.1 and BA.2 are antigenically most distinct from D614G, associated with immune escape and likely requiring vaccine updates to ensure vaccine effectiveness.
Nurses’ Perceptions regarding Current Skills in Minimizing Patient’s Aggression at a selected Psychiatric hospital in Lesotho
Authors: Rathobei Libuseng Moureen , Nyangu Isabel , Dube Makhosazane Barbara 
Published: January 2022

AbstractBackgroundMeta-analysis of international literature indicate high frequencies of aggression in mental health setting. Several studies indicate that among professional health workers, nurses are more likely than other staff members to experience aggressive incidences from patients. Furthermore, based on cause, nurses apply range of interventions in managing aggression, however, despite their perceived value of their intervention in managing aggression, no single intervention is sufficient for handling aggressive patients to stay in control in wards. Despite high priority placed on patient aggression management, insufficient research studies have been conducted on nurses’ perceptions regarding current skills in minimizing patient’s aggression.ObjectivesThe purpose of the study was to describe nurses’ perceptions regarding current assessment skills in minimizing patient’s aggression at selected Psychiatric hospital.MethodologyNon-experimental, exploratory, descriptive research design was used to guide research process. All-inclusive sampling method was used with 119 nurses as respondents. Data was collected by means of a questionnaire, analyzed using SPSS version 25. Descriptive statistics procedure was used to present findings of the study.ResultsMinority of respondents, (n=27) 22.7% agreed that their current assessment skills for minimizing patients’ aggression were good compared to majority of respondents, (n=92) 77.3%, who expressed a different opinion. This suggests that there is limited current assessment skills in identifying high risk aggressive patients in a selected Psychiatric hospital.ConclusionThe findings of study indicate that there is limited current assessment skills in minimizing patients’ aggression at selected Psychiatric hospital. Therefore, there is need to provide comprehensive information on nurses’ current skills in minimizing patients’ aggression to obtain richer information.
Shielding individuals at high risk of COVID-19: a micro-simulation study
Authors: van Zandvoort Kevin , Favas Caroline , Checchi Francesco 
Published: January 2022

AbstractBackgroundOne of the proposed interventions for mitigating COVID-19 epidemics, particularly in low-income and crisis-affected settings, is to physically isolate individuals known to be at high risk of severe disease and death due to age or co-morbidities. This intervention, known as ‘shielding’, could be implemented in various ways. If shielded people are grouped together in residences and isolation is imperfect, any introduction of infections within the shielding group could cause substantial mortality and thus negate the intervention’s benefits. We explored the effectiveness of shielding under various modalities of implementation and considered mitigation measures to reduce its possible harms.MethodsWe used an individual-based mathematical model to simulate the evolution of a COVID-19 epidemic in a population of which a fraction above a given age cut-off are relocated to shielding residences, in which they have variable levels of contacts with their original household, the outside world and fellow shielding residents. We set our simulation with the context of an internally displaced persons’ camp in Somaliland, for which we had recently collected data on household demographics and social mixing patterns. We compared an unmitigated epidemic with a shielding intervention accompanied by various measures to reduce the risk of virus introduction and spread within the shielding residences. We did sensitivity analyses to explore parameters such as residence size, reduction in contacts, basic reproduction number, and prior immunity in the population.ResultsShielded residences are likely to be breached with infection during the outbreak. Nonetheless, shielding can be effective in preventing COVID-19 infections in the shielded population. The effectiveness of shielding is mostly affected by the size of the shielded residence, and by the degree by which contacts between shielded and unshielded individuals are reduced. Reductions in contacts between shielded individuals could further increase the effectiveness of shielding, but is only effective in larger shielded residences. Large shielded residences increase the risk of infection, unless very large reductions in contacts can be achieved. In epidemics with a lower reproduction number, the effectiveness of shielding could be negative effectiveness.DiscussionShielding could be an effective method to protect the most at-risk individuals. It should be considered where other measures cannot easily be implemented, but with attention to the epidemiological situation. Shielding should only be implemented through small to medium-sized shielding residences, with appropriate mitigation measures such as reduced contact intensity between shielded individuals and self-isolation of cases to prevent subsequent spread.
Magnetic torque-driven living microrobots for enhanced tumor infiltration
Authors: Gwisai T. , Mirkhani N. , Christiansen M. G. , Nguyen T.T. , Ling V. , Schuerle S. 
Published: January 2022

AbstractBacterial microrobots combining self-propulsion and magnetic guidance are increasingly recognized as promising drug delivery vehicles for targeted cancer therapy. Thus far, control strategies have either relied on poorly scalable magnetic field gradients or employed directing magnetic fields with propulsive forces limited by the bacterial motor. Here, we present a magnetic torque-driven actuation scheme based on rotating magnetic fields to wirelessly control Magnetospirillum magneticum AMB-1 bearing versatile liposomal cargo. We observed a 4-fold increase in conjugate translocation across a model of the vascular endothelium and found that the primary mechanism driving this increased transport is torque-driven surface exploration at the cell interface. Using spheroids as a 3D tumor model, fluorescently labeled bacteria colonized their core regions with up to 21-fold higher signal in samples exposed to rotating magnetic fields. In addition to enhanced transport, we demonstrated the suitability of this magnetic stimulus for simultaneous actuation and inductive detection of AMB-1. Finally, we demonstrated that RMF significantly enhances AMB-1 tumor accumulation in vivo following systemic intravenous administration in mice. Our findings suggest that scalable magnetic torque-driven control strategies can be leveraged advantageously with biohybrid microrobots.One-Sentence SummaryMagnetic torque-driven motion enhances infiltration of living microrobots across physiological barriers both in vitro and in vivo.
Mesenchymal tumor organoid models recapitulate rhabdomyosarcoma subtypes
Authors: Meister Michael T. , Groot Koerkamp Marian J. A. , de Souza Terezinha , Breunis Willemijn B. , Frazer-Mendelewska Ewa , Brok Mariël , DeMartino Jeff , Manders Freek , Calandrini Camilla , Kerstens Hinri H. D. , Janse Alex , Dolman M. Emmy M. , Eising Selma , Langenberg Karin P. S. , van Tuil Marc , Knops Rutger R. G. , van Scheltinga Sheila Terwisscha , Hiemcke-Jiwa Laura S. , Flucke Uta , Merks Johannes H. M. , van Noesel Max M. , Tops Bastiaan B. J. , Hehir-Kwa Jayne Y. , Kemmeren Patrick , Molenaar Jan J. , van de Wetering Marc , van Boxtel Ruben , Drost Jarno , Holstege Frank C. P. 
Published: January 2022

SummaryRhabdomyosarcomas (RMS) are mesenchyme-derived tumors and the most common childhood soft tissue sarcomas. Treatment is intense, with a nevertheless poor prognosis for high-risk patients. Discovery of new therapies would benefit from additional preclinical models. Here we describe the generation of a collection of pediatric RMS tumor organoid (tumoroid) models comprising all major subtypes. For aggressive tumors, tumoroid models can often be established within four to eight weeks, indicating the feasibility of personalized drug screening. Molecular, genetic and histological characterization show that the models closely resemble the original tumors, with genetic stability over extended culture periods of up to six months. Importantly, drug screening reflects established sensitivities and the models can be modified by CRISPR/Cas9 withTP53knockout in an embryonal RMS model resulting in replicative stress drug sensitivity. Tumors of mesenchymal origin can therefore be used to generate organoid models, relevant for a variety of preclinical and clinical research questions.
Tree House Explorer: A Novel Genome Browser for Phylogenomics
Authors: Harris Andrew J. , Foley Nicole M. , Williams Tiffani L. , Murphy William J. 
Published: January 2022

AbstractTree House Explorer (THEx) is a genome browser that integrates phylogenomic data and genomic annotations into a single interactive platform for combined analysis. THEx allows users to visualize genome-wide variation in evolutionary histories and genetic divergence on a chromosome-by-chromosome basis, with continuous sliding window comparisons to gene annotations, recombination rates, and other user-specified, highly customizable feature annotations. THEx provides a new platform for interactive phylogenomic data visualization to analyze and interpret the diverse evolutionary histories woven throughout genomes. Hosted on Conda, THEx integrates seamlessly into new or pre-existing workflows.
Integrated genomic analysis of AgRP neurons reveals that IRF3 regulates leptin’s hunger-suppressing effects
Authors: Heyward Frankie D. , Liu Nan , Jacobs Christopher , Ivison Rachael , Machado Natalia , Uner Aykut , Srinivasan Harini , Patel Suraj J. , Gulko Anton , Sermersheim Tyler , Orkin Stuart H. , Tsai Linus , Rosen Evan D. 
Published: January 2022

ABSTRACTAgRP neurons in the arcuate nucleus of the hypothalamus (ARC) coordinate homeostatic changes in appetite associated with fluctuations in food availability and leptin signaling. Identifying the relevant transcriptional regulatory pathways in these neurons has been a priority, yet such attempts have been stymied due to their low abundance and the rich cellular diversity of the ARC. Here we generated AgRP neuron-specific transcriptomic and chromatin accessibility profiles during opposing states of fasting-induced hunger and leptin-induced hunger suppression. Cis-regulatory analysis of these integrated datasets enabled the identification of 28 putative hunger-promoting and 29 putative hunger-suppressing transcriptional regulators in AgRP neurons, 16 of which were predicted to be transcriptional effectors of leptin. Within our dataset, Interferon regulatory factor 3 (IRF3) emerged as a leading candidate mediator of leptin-induced hunger-suppression. Gain- and loss-of-function experiments in vivo confirm the role of IRF3 in mediating the acute satiety-evoking effects of leptin in AgRP neurons, while live-cell imaging in vitro indicate that leptin can activate neuronal IRF3 in a cell autonomous manner. Finally, we employ CUT&RUN to uncover direct transcriptional targets of IRF3 in AgRP neurons in vivo. Thus, our findings identify AgRP neuron-expressed IRF3 as a key transcriptional effector of the hunger-suppressing effects of leptin.
Hippocampal Volume, Neurite Density and Trace Eye-Blink Conditioning in Young Children
Authors: Vieites Vanessa , Ralph Yvonne , Reeb-Sutherland Bethany , Dick Anthony Steven , Mattfeld Aaron T. , Pruden Shannon M. 
Published: January 2022

AbstractThe current study examined the relations between hippocampal structure (e.g., volume and neurite density) and performance on a trace eye blink conditioning (EBC) task in young children. Our first aim assessed whether individual differences in hippocampal volume were associated with trace EBC performance, using both percent Conditioned Responses (% CR) and CR onset latency or the average latency (ms) at which the child started their blink, as measures of hippocampal-dependent associative learning. Our second aim evaluated whether individual differences in hippocampal neurite density were associated with EBC performance using the same outcome measures. Typically developing 4- to 6-year-olds (N = 31; 14 girls; Mage = 5.67; SDage = 0.89) completed T1 and diffusion-weighted MRI scans and a 15-minute trace eyeblink conditioning task outside of the scanner. % CR and CR onset latency were computed across all tone-puff and tone-alone trials. While hippocampal volume was not associated with any of our EBC measures, greater hippocampal neurite density bilaterally, was associated with later CR onset. In other words, children with greater left and right hippocampal neurite density blinked closer to the US (i.e., air puff) than children with less hippocampal neurite density, indicating that structural changes in the hippocampus assisted in the accurate timing of conditioned responses.