bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prostate-Specific Membrane Antigen–Avid Bone Metastases From Urothelial Carcinoma of the Bladder
Authors: Zhao Bo , Dong Aisheng , Zuo Changjing 
Published: April 2022

Abstract
Prostate-specific membrane antigen (PSMA) PET findings of urothelial carcinoma were rarely reported. We describe 18F-FDG PET/CT and 68Ga-PSMA-11 PET/MRI findings in a case of urothelial carcinoma of the bladder with bone metastases in the sternum, ribs, spine, pelvis, and femurs. The bone metastases showed isodensity to hyperdensity and mild to intense FDG uptake on FDG PET/CT and moderate to intense PSMA uptake on PSMA PET/MRI. PSMA PET/MRI more clearly delineated the bone metastases compared with FDG PET/CT.
Review of the Sonographic Features of Interpectoral (Rotter) Lymph Nodes in Breast Cancer Staging
Authors: Engel Adam J. , Shin Kyungmin , Adrada Beatriz E. , Moseley Tanya W. , Krishnamurthy Savitri , Whitman Gary J. 
Published: April 2022

Abstract
This article reviews the ultrasound evaluation and staging of breast cancer with respect to the involvement of interpectoral (Rotter) lymph nodes. The primary objective is to demonstrate and assess the characteristic sonographic findings of interpectoral (Rotter) lymph nodes to help provide accurate nodal staging information. We aim to provide a comprehensive review and serve as an imaging guide for the identification and evaluation of Rotter lymph nodes. The detection of abnormalities and pathologic features of metastatic axillary nodal disease in the interpectoral region is reviewed, and the impact on clinical management and treatment is discussed. In the radiology literature, there is no comprehensive review of the sonographic appearance and evaluation of Rotter lymph nodes.
Role Clarity and Interprofessional Colleagues in Psychological Safety
Authors: Klenke-Borgmann Laura , DiGregorio Heiddy , Cantrell Mary Ann 
Published: April 2022

Summary Statement
Psychological safety in high-fidelity simulation-based experiences ensures that learners feel safe with new experiences in the service of learning. This article is a faculty reflection on breaches in the psychological safety among nursing students in 2 independent, high-fidelity simulation-based experience studies that were conducted in 2019. Demonstrated breaches in psychological safety included fear and anxiety in the sole provider role in multiple-patient simulations and incivility directed toward nursing students in a primary nurse role in interprofessional simulations. This article adds to the growing literature on psychological safety by sharing important lessons learned regarding role clarity and interprofessional colleagues, proposing recommendations, and providing suggestions for future research on psychological safety.
A retrospective cross-sectional analysis of community perceptions of flu and COVID-19 vaccines at Turtle Creek Primary Care Center
Authors: Murali Anjana , Sojati Jorna , Levochkina Marina , Pressimone Catherine , Griffith Kobi , Fan Erica , Dakroub Allie 
Published: April 2022

ABSTRACTBackgroundInfluenza (flu) and COVID-19 vaccination rates are subpar across the US, especially in racial and/or socioeconomic minority groups who are understudied in public health literature.ObjectiveThe objective of this study was to elucidate the attitudes of Turtle Creek patients towards flu and COVID-19 vaccines, with the goal of establishing targetable vaccine education gaps and ultimately increasing vaccine uptake in the community.Design/PatientsThis study was conducted as a retrospective cross-sectional analysis. Authors completed 123 patient phone surveys of patients cared for at the Turtle Creek Primary Care Center inquiring about flu and COVID-19 infection status and vaccination uptake (August 26 - October 10, 2021).Approach/Key ResultsOur data revealed a significant association between COVID-19 and flu vaccine acceptance. Additionally, we found a strong association between vaccine acceptance and age, with older patients being more likely to be vaccinated against COVID-19. Using multivariable logistic regression models, we assessed how flu and COVID-19 vaccine acceptance was affected by informational sources participants trusted most. In the COVID-19 models, those who cited “trusting medical professionals” had higher odds of vaccine acceptance while participants who cited “trusting social media” had significantly decreased odds of vaccine acceptance.ConclusionOur study revealed significant trends for flu and COVID-19 vaccine acceptance by sociodemographic factors and trust in the medical system. Using these data, we can create future interventions to overcome vaccine hesitancy.
Development of a Highly Sensitive Serum Neurofilament Light Chain Assay on an Automated Immunoassay Platform
Authors: Lee Stephen , Plavina Tatiana , Singh Carol M , Xiong Kuangnan , Qiu Xiaolei , Rudick Richard A , Calabresi Peter A , Stevenson Lauren , Graham Danielle , Raitcheva Denitza , Green Christopher , Matias Madeleine , Uzgiris Arejas J 
Published: April 2022

ABSTRACTBackgroundNeurofilament light chain (NfL) is an axonal cytoskeletal protein that is released into the extracellular space following neuronal or axonal injury associated with neurological conditions such as multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS), and other diseases. NfL is detectable in cerebrospinal fluid (CSF) and blood. Numerous studies in MS have demonstrated that NfL correlates with disease activity, predicts disease progression, and is reduced by treatment with MS disease-modifying drugs, making NfL an attractive candidate to supplement existing clinical and imaging measures in MS. However, for NfL to achieve its potential as a clinically useful biomarker for clinical decision-making or drug development, a standardized, practical, widely accessible assay is needed. Our objective was to validate the analytical performance of the novel serum neurofilament light (sNfl) assay on the ADVIA Centaur® XP immunoassay system.MethodsThe research assay was evaluated on the ADVIA Centaur XP immunoassay system from Siemens Healthineers. The lower limit of quantitation (LLoQ), intra-assay variation, assay range, cross-reactivity with neurofilament medium and heavy chains, and effect of interfering substances were determined. NfL assay values in serum and CSF were compared with radiological and clinical disease activity measures in patients with MS and ALS, respectively. This assay was further optimized to utilize serum, plasma, and CSF sample types and transferred to Siemens’ CLIA laboratory, where it was analytically validated as a laboratory-developed test.ResultsIn this study, a LLoQ of 1.85 pg/mL, intra-assay variation of <6%, and an assay range of up to 646 pg/mL were demonstrated. A cross-reactivity of <0.7% with neurofilament medium and heavy chains was observed, and the assay was not significantly affected by various interfering substances encountered in clinical specimens. Serum and CSF NfL assay values were associated with radiological and clinical disease activity measures in patients with MS and ALS, respectively.ConclusionThe analytical performance of the NfL assay fulfilled all acceptance criteria; therefore, we believe the assay is acceptable for use in both research and clinical practice settings to determine elevated sNfL levels in patients.
In vitro and in vivo antioxidant therapeutic evaluation of Dodonaea viscosa Jacq.
Authors: Khan Siraj , Rehman Mujeeb Ur , Khan Muhammad Zafar Irshad , Muhammad Khan , Haq Ihsan Ul , Khan Muhammad Ijaz 
Published: April 2022

ABSTRACTContextNatural antioxidants are vital to promote health and treat critical diseased conditions in the modern healthcare system.ObjectiveThis work adds to the index of natural medicines by exploring the antioxidant potential of Dodonaea viscosa Jacq. (Plant-DV).Material and methodsThe aqueous extract of leaves and seeds from plant-DV in freshly prepared phosphate buffer is evaluated for antioxidant potential. In vitro antioxidant potential of the nascent and oxidatively stressed extracts was analyzed through glutathione (GSH) assay, hydrogen peroxide (H2O2) scavenging effect, glutathione-S-transferase (GST) assay, and catalase (CAT) activity. In vivo therapeutic assessment is performed in Wistar Albino rats using vitamin C as a positive control. The livers and kidneys of individual animals are probed for glutathione, glutathione-S-transferase, and catalase activities.ResultsSeeds have GSH contents (59.61 µM) and leaves (32.87 µM) in the fresh aqueous extracts. The hydrogen peroxide scavenging effect of leaves is superior to seeds with 17.25% and 14.18% respectively after 30 min incubation. However, oxidatively stressed extracts with AgI and HgII show declining GSH and GST levels. The plant extracts are non-toxic in rats at 5000 mg/Kg body weight. Liver and kidneys homogenate reveal an increase in GSH, GST, and CAT levels after treatment with 150 ± 2 mg/kg and 300 ± 2 mg/kg body weight plant extract compared with normal saline-treated negative and vitamin C treated positive control.Discussion and ConclusionThe crude aqueous extracts of leaves and seeds of plant DV show promising antioxidant potential both in in vitro and in vivo evaluation.
A Mixed Methods Study Evaluating Acceptability of a Daily COVID-19 Testing Regimen with a Mobile-App Connected, At-Home, Rapid Antigen Test: Implications for Current and Future Pandemics
Authors: Nguyen Nadia , Lane Benjamin , Lee Sangwon , Gorman Sharon Lipsky , Wu Yumeng , Li Alicia , Lu Helen , Elhadad Noemie , Yin Michael , Meyers Kathrine 
Published: April 2022

AbstractBackgroundWidespread use of at-home rapid COVID-19 antigen tests has been proposed as an important public health intervention to interrupt chains of transmission. Antigen tests may be preferred over PCR because they provide on-demand results for relatively low cost and can identify people when they are most likely to be infectious, particularly when used daily. Yet the extent to which a frequent antigen testing intervention will result in a positive public health impact for COVID-19 will depend on high acceptability and high adherence to such regimens.MethodsWe conducted a mixed-methods study assessing acceptability of and adherence to a daily at-home mobile-app connected rapid antigen testing regimen among employees of a US-based media company. Acceptability was assessed across seven domains of the Theoretical Framework of Acceptability.ResultsAmong 31 study participants, acceptability of the daily testing intervention was generally high, with participants reporting high perceived effectiveness, intervention coherence, and self-efficacy; positive affective attitude; acceptable degree of burden and opportunity cost; and assessing the intervention as ethical. 71% reported a preference to test daily using an at-home antigen test than weekly employment-based PCR. Mean adherence to the 21-day testing regimen was 88% with 43% of participants achieving 100% adherence, 48% testing at least every other day, and 10% testing less than every other day.ConclusionsDespite overall high acceptability and adherence, we identified three implementation challenges that must be addressed for frequent serial testing for COVID-19 to be implemented at scale and have a positive public health impact. First, users need guidance on how and when to adapt testing frequencies to different epidemiological conditions. Second, users and institutions need guidelines for how to safely store and share test results. Third, implementation of serial testing strategies must prioritize health equity and protect those most vulnerable to COVID-19.
Redox regulation of the SARS-CoV-2 main protease provides new opportunities for drug design
Authors: Funk Lisa-Marie , Poschmann Gereon , Chari Ashwin , von Pappenheim Fabian Rabe , Stegmann Kim-Maren , Dickmanns Antje , Eulig Nora , Wensien Marie , Paknia Elham , Heyne Gabi , Penka Elke , Pearson Arwen R. , Berndt Carsten , Fritz Tobias , Bazzi Sophia , Uranga Jon , Mata Ricardo A. , Dobbelstein Matthias , Hilgenfeld Rolf , Curth Ute , Tittmann Kai 
Published: April 2022

AbstractBesides vaccines, the development of antiviral drugs targeting SARS-CoV-2 is critical for stopping the current COVID-19 pandemic and preventing future outbreaks. The SARS-CoV-2 main protease (Mpro), a cysteine protease with essential functions in viral replication, has been validated as an effective drug target. Here, we show that Mpro is subject to redox regulation and reversibly switches between the enzymatically active dimer and the functionally dormant monomer through redox modifications of cysteine residues. These include sulfenylation, disulfide formation between the catalytic cysteine and a proximal cysteine, and generation of an allosteric lysine-cysteine SONOS bridge that is required for structural stability under oxidative stress conditions, such as those exerted by the innate immune system. We identify homo- and heterobifunctional reagents that mimic the redox switching and possess antiviral activity. The discovered redox switches are conserved in main proteases from other coronaviruses, e.g. MERS and SARS-CoV, indicating their potential as common druggable sites.
Functional Recovery from Human Induced Pluripotent Stem Cell-Derived Dopamine Neuron Grafts is Dependent on Neurite Outgrowth
Authors: Hills Rachel , Mossman Jim A. , Bratt-Leal Andres M. , Tran Ha , Williams Roy M. , Stouffer David G. , Sokolova Irina V. , Sanna Pietro P. , Loring Jeanne F. , Lelos Mariah J. 
Published: April 2022

SummaryTransplantation of human pluripotent stem cell-derived dopaminergic (DA) neurons is an emerging therapeutic strategy for Parkinson’s disease (PD). In this study, we demonstrate, for the first time, that that functional recovery after DA neuron transplant is critically dependent on graft-host integration, and not dependent on graft size or DA neuron content. Specifically, in anticipation of an autologous DA neuron transplant strategy, we studied two human induced pluripotent stem cell lines derived from people with idiopathic PD. We confirmed the cells’ ability to differentiate into mature DA neurons in vitro by assessing electrophysiology and depolarization-induced neurotransmitter release. To evaluate efficacy, we transplanted DA neuron precursors into a hemiparkinsonian rat model. We differentiated the cell lines for either 18 (d18) or 25 days (d25) to investigate the effect of cell maturity on efficacy. We found comparable graft survival in d18 and d25 groups from both cell lines, but behavioral analysis revealed that only d18 preparations, from both cell lines, resulted in recovery of motor impairments. Immunohistochemical analysis did not reveal any DA neuron-associated markers that correlated with efficacy. However, we found striking and consistent differences in graft neurite outgrowth between the two culture timepoints. The functional grafts from d18 cells had more outgrowth than non-functional d25 grafts. A time course of gene expression during differentiation of the cell lines revealed differences in genes associated with DA neuron development and neurite plasticity. These results are the first to demonstrate that graft-host integration, and not DA neuron content, is key to graft-induced functional recovery. The gene expression profiling may offer insight into the optimal developmental stage for graft efficacy.
Female behavior drives the formation of distinct social structures in C57BL/6J versus wild-derived outbred mice in field enclosures
Authors: Vogt Caleb C. , Zipple Matthew N. , Sprockett Daniel D. , Miller Caitlin H. , Hardy Summer X. , Arthur Matthew K. , Greenstein Adam M. , Colvin Melanie S. , Michel Lucie M. , Moeller Andrew H. , Sheehan Michael J. 
Published: April 2022

AbstractSocial behavior and social organization have major influences on individual health and fitness. Yet, biomedical research focuses on studying a few genotypes under impoverished social conditions. Understanding how lab conditions have modified social organizations of model organisms, such as lab mice, relative to natural populations is a missing link between socioecology and biomedical science. Using a common garden design, we describe the formation of social structure in the well-studied laboratory mouse strain, C57BL/6J, in replicated mixed-sex populations over 10-day trials compared to control trials with wild-derived outbred house mice in outdoor field enclosures. We focus on three key features of mouse social systems: (i) territory establishment in males, (ii) female social relationships, and (iii) the social networks formed by the populations. Male territorial behaviors were similar but muted in C57 compared to wild-derived mice. Female C57 sharply differed from wild-derived females, showing little social bias toward cage mates and exploring substantially more of the enclosures compared to all other groups. Female behavior consistently generated denser social networks in C57 than in wild-derived mice. The repeatable societies formed under field conditions highlights opportunities to experimentally study the interplay between society and individual biology using model organisms.
Clonal spreading of tumor-infiltrating T cells underlies the robust antitumor immune responses
Authors: Aoki Hiroyasu , Tsunoda Mikiya , Ogiwara Haru , Shimizu Haruka , Abe Haruka , Abe Takaya , Shichino Shigeyuki , Matsushima Kouji , Ueha Satoshi 
Published: April 2022

AbstractThe repertoire of tumor-infiltrating T cells is an emerging perspective for characterizing effective antitumor T-cell responses. Oligoclonal expansion of tumor T-cell repertoire has been evaluated; however, their association with antitumor effects is unclear. We demonstrated that the polyclonal fraction of the tumor-reactive T-cell repertoire consisting of relatively minor clones increased in tumor-bearing mice treated with anti-PD-L1 or anti-CD4 monoclonal antibody, which was correlated with antitumor effect. Meanwhile, the size of the oligoclonal fraction consisting of major clones remained unchanged. Moreover, the polyclonal fraction was enriched in progenitor exhausted T cells, which are essential for a durable antitumor response, and was more dependent on CCR7+ migratory dendritic cells, which are responsible for priming tumor-reactive T cells in the tumor-draining lymph nodes. These results suggest that the expansion of diverse tumor-reactive clones (“clonal spreading”) is an important mechanism by which anti-PD-L1 and anti-CD4 treatments induce robust and durable antitumor T-cell responses.
Effects of abiotic environment on invertebrate herbivory depend on plant community context in a montane grassland
Authors: Halliday Fletcher W. , Cappelli Seraina L , Laine Anna-Liisa 
Published: April 2022

AbstractInvertebrate herbivores are important and diverse, and their abundance and impacts are expected to undergo unprecedented shifts under climate change. Yet, past studies of invertebrate herbivory have documented a wide variety of responses to changing temperature, making it challenging to predict the direction and magnitude of these shifts. One explanation for these idiosyncratic responses is that changing environmental conditions may drive concurrent changes in plant communities and herbivore traits. Thus, the impacts of changing temperature on herbivory might depend on how temperature combines and interacts with characteristics of plant communities and the herbivores that occupy them. Here, we test this hypothesis by surveying invertebrate herbivory in 220, 0.5 meter-diameter herbaceous plant communities along a 1101-meter elevational gradient. Our results suggest that increasing temperature can drive community-level herbivory via at least three overlapping mechanisms: increasing temperature directly reduced herbivory, indirectly affected herbivory by reducing phylogenetic diversity of the plant community, and indirectly affected herbivory by altering the effects of functional and phylogenetic diversity on herbivory. Consequently, increasing functional diversity of plant communities had a negative effect on herbivory, but only in colder environments while a positive effect of increasing phylogenetic diversity was observed in warmer environments. Moreover, accounting for differences among herbivore feeding guilds considerably improved model fit, because different herbivore feeding guilds varied in their response to temperature and plant community composition. Together, these results highlight the importance of considering both plant and herbivore community context in order to predict how climate change will alter invertebrate herbivory.
Predicting A/B compartments from histone modifications using deep learning
Authors: Zheng Suchen , Thakkar Nitya , Harris Hannah L. , Zhang Megan , Liu Susanna , Gerstein Mark , Aiden Erez Lieberman , Rowley M. Jordan , Noble William Stafford , Gürsoy Gamze , Singh Ritambhara 
Published: April 2022

ABSTRACTGenomes fold into organizational units in the 3D space that can influence critical biological functions. In particular, the organization of chromatin into A and B compartments segregates its active regions from inactive regions. Compartments, evident in Hi-C contact matrices, have been used to describe cell-type specific changes in the A/B organization. However, obtaining Hi-C data for all cell and tissue types of interest is prohibitively expensive, which has limited the widespread consideration of compartment status. We present a prediction tool called Compartment prediction using Recurrent Neural Network (CoRNN) that models the relationship between the compartmental organization of the genome and histone modification enrichment. Our model predicts A/B compartments, in a cross-cell type setting, with an average area under the ROC curve of 90.9%. Our cell type-specific compartment predictions show high overlap with known functional elements. We investigate our predictions by systematically removing combinations of histone marks and find that H3K27ac and H3K36me3 are the most predictive marks. We then perform a detailed analysis of loci where compartment status cannot be accurately predicted from these marks. These regions represent chromatin with ambiguous compartmental status, likely due to variations in status within the population of cells. These ambiguous loci also show highly variable compartmental status between biological replicates in the same GM12878 cell type. Finally, we demonstrate the generalizability of our model by predicting compartments in independent tissue samples. Our software and trained model are publicly available at https://github.com/rsinghlab/CoRNN.
Gene regulation by synergism between mRNA decay and gene transcription
Authors: García-Martínez José , Singh Abhyudai , Medina Daniel , Chávez Sebastián , Pérez-Ortín José E. 
Published: April 2022

AbstractIt has become increasingly clear in the last few years that gene expression in eukaryotes is not a linear process starting from transcription in the nucleus to the cytoplasm, but a circular one where the mRNA level is controlled by crosstalk between nuclear transcription and cytoplasmic decay pathways. One of the possible purposes of this crosstalk is to keep the mRNA level approximately constant. This is called mRNA buffering and happens when transcription and mRNA degradation act at compensatory rates. However, if transcription and mRNA degradation act synergistically, enhanced gene expression regulation would occur. In this work we mathematically modeled the effects of RNA binding proteins (RBP) when they have positive or negative effects on mRNA synthesis and decay rates. We found that they can buffer or enhance gene expression responses depending on their respective effects on transcription and mRNA stability. Then we analyzed new and previously published genomic datasets obtained for several yeast mutants related to either transcription or mRNA decay, but they are not known to possess activity in the other process. We show that some of them, which were presumed only transcription factors (Sfp1) or only decay factors (Puf3, Upf2/3), may represent examples of RBPs that make specific synergistic crosstalk to enhance the control of the mRNA levels of their target genes by combining antagonistic effects on transcriptional and mRNA stability.