bluuebunny/crossref_metadata_2025_split huggingface dataset:
Optimizing Parameters for Using the Parallel Auditory Brainstem Response (pABR) to Quickly Estimate Hearing Thresholds
Authors: Polonenko Melissa J , Maddox Ross K 
Published: May 2021

ABSTRACTObjectivesTimely assessments are critical to providing early intervention and better hearing and spoken language outcomes for children with hearing loss. To facilitate faster diagnostic hearing assessments in infants, the authors developed the parallel auditory brainstem response (pABR), which presents randomly timed trains of tone pips at five frequencies to each ear simultaneously. The pABR yields high-quality waveforms that are similar to the standard, single-frequency serial ABR but in a fraction of the recording time. While well-documented for standard ABRs, it is yet unknown how presentation rate and level interact to affect responses collected in parallel. Furthermore, the stimuli are yet to be calibrated to perceptual thresholds. Therefore, this study aimed to determine the optimal range of parameters for the pABR and to establish the normative stimulus level correction values for the ABR stimuli.DesignTwo experiments were completed, each with a group of 20 adults (18 – 35 years old) with normal hearing thresholds (≤ 20 dB HL) from 250 to 8000 Hz. First, pABR electroencephalographic (EEG) responses were recorded for six stimulation rates and two intensities. The changes in component wave V amplitude and latency were analyzed, as well as the time required for all responses to reach a criterion signal-to-noise ratio of 0 dB. Second, behavioral thresholds were measured for pure tones and for the pABR stimuli at each rate to determine the correction factors that relate the stimulus level in dB peSPL to perceptual thresholds in dB nHL.ResultsThe pABR showed some adaptation with increased stimulation rate. A wide range of rates yielded robust responses in under 15 minutes, but 40 Hz was the optimal singular presentation rate. Extending the analysis window to include later components of the response offered further time-saving advantages for the temporally broader responses to low frequency tone pips. The perceptual thresholds to pABR stimuli changed subtly with rate, giving a relatively similar set of correction factors to convert the level of the pABR stimuli from dB peSPL to dB nHL.ConclusionsThe optimal stimulation rate for the pABR is 40 Hz, but using multiple rates may prove useful. Perceptual thresholds that subtly change across rate allow for a testing paradigm that easily transitions between rates, which may be useful for quickly estimating thresholds for different configurations of hearing loss. These optimized parameters facilitate expediency and effectiveness of the pABR to estimate hearing thresholds in a clinical setting.HighlightsThe pABR yields robust responses across stimulus rates and intensities.The optimal rate is 40 Hz, but using multiple rates may prove useful.The pABR shows some adaptation with increased stimulation rate.Extended analysis windows improve response detection for low stimulus frequencies.Behavioral thresholds subtly change across pABR rate, giving similar dB nHL values.
Force profile of the two-handed hardstyle kettlebell swing performed by an RKC-certified instructor
Authors: Meigh Neil J. , Hing Wayne A. , Schram Ben , Keogh Justin W.L. 
Published: May 2021

AbstractBackgroundThe effects of hardstyle kettlebell training are increasingly cited in strength and conditioning research, yet reference data from a proficient swing is scarce. The aim of this exploratory study was to investigate the force profile of a two-handed hardstyle swing performed by a Russian Kettlebell Challenge (RKC) instructor.MethodsThe subject is a 44-year-old male, body mass 75.6 kg, height 173.5 cm, with six years of regular hardstyle training experience. Two-handed hardstyle swings were performed with a series of incremental mass kettlebells (8-68 kg). Ground reaction force (GRFs) was obtained from a floor-mounted force platform. Force-time curves (FTCs), peak force, forward force, rate of force development (RFD) and swing cadence were investigated.ResultsData revealed the FTC of a proficient swing is highly consistent and dominated by a single force peak (mean SD = 47 N), with a profile that remained largely unchanged to 24 kg. Pearson correlation analysis revealed a very strong positive correlation in peak force with kettlebell mass (r = 0.95), which increased disproportionately from the lightest to heaviest kettlebells; net peak force increased from 8.36 ± 0.75 N.kg-1 (0.85 × BW) to 12.82 ± 0.39 N.kg-1 (1.3× BW). There was a strong negative correlation between RFD and kettlebell mass (r = 0.82) that decreased from 39.2 N.s-1.kg-1 to 21.5 N.s-1.kg-1. There was a very strong positive correlation in forward ground reaction force with kettlebell mass (r = 0.99), expressed as a ratio of vertical ground reaction, that increased from 0.092 (9.2%) to 0.205 (20.5%). Swing cadence exceeded 40 swings per minute (SPM) with all kettlebells.ConclusionOur findings challenge some of the popular beliefs of the hardstyle kettlebell swing. Consistent with hardstyle practice, and previous kinematic analysis of expert and novice, force-time curves show a characteristic single large force peak, differentiating passive from active shoulder flexion. Ground reaction force did not increase proportionate to kettlebell mass, with a magnitude of forward force smaller than described in practice. These results could be useful for coaches and trainers wanting to improve athletic performance, and healthcare providers using the kettlebell swing for therapeutic purposes. Findings from this study were used to inform the BELL Trial, a pragmatic controlled trial of kettlebell training with older adults. www.anzctr.org.au ACTRN12619001177145.
Expression of GRINA Correlates with Prognosis in Human Cancers: A Pan-cancer Analysis
Authors: Islam S. M. Riazul , Saha Subbroto Kumar , El-Sappagh Shaker , Tariq Faisal , Das Joydeep , Afzal Muhammad , Cho Ssang-Goo 
Published: May 2021

AbstractGRINA is an emerging target for cancer therapy. However, the role of GRINA expression and its correlation with cancer patient survival has not been comprehensively studied. Here, we found that mRNA and protein expression of GRINA was upregulated in breast, colon, gastric, and prostate cancers and negatively correlated with patient survival. Also, the upregulation of GRINA expression is associated with hypomethylation of its promoter region. Our GRINA-miRNAs network analysis revealed potential regulatory miRNAs regulating the GRINA expression and its downstream pathways. Next, functional enrichment and pathway analysis of genes commonly co-express with GRINA in breast, colon, gastric, and prostate cancers revealed GRINA regulatory pathways. Concurrently, our upstream regulator analysis revealed possible kinases, transcription factors, and proteins that may potentially regulate GRINA. Overall, this study demonstrates the prognostic significance of GRINA expression and identifies potential regulatory mechanisms, which might have significant implications in targeted therapies for human cancers.
Diverse classes of constraints enable broader applicability of a linear programming-based dynamic metabolic modeling framework
Authors: Lee Justin Y. , Styczynski Mark P. 
Published: May 2021

AbstractCurrent metabolic modeling tools suffer from a variety of limitations, from scalability to simplifying assumptions, that preclude their use in many applications. We recently created a modeling framework, LK-DFBA, that addresses a key gap: capturing metabolite dynamics and regulation while retaining a potentially scalable linear programming structure. Key to this framework’s success are the linear kinetics and regulatory constraints imposed on the system. However, while the linearity of these constraints reduces computational complexity, it may not accurately capture the behavior of many biochemical systems. Here, we developed three new classes of LK-DFBA constraints to better model interactions between metabolites and the reactions they regulate. We tested these new approaches on several synthetic and biological systems, and also performed the first-ever comparison of LK-DFBA predictions to experimental data. We found that no single constraint approach was optimal across all systems examined, and systems with the same topological structure but different parameters were often best modeled by different types of constraints. However, we did find that the optimal constraint approach was generally robust to local perturbations of the system, indicating that just a single wild-type dataset could allow identification of the ideal constraint for a given system. These results suggest that the availability of multiple constraint approaches will allow LK-DFBA to model a wider range of metabolic systems.
Leveraging the mass balances of cellular metabolism to infer absolute concentrations from relative abundance metabolomics data
Authors: Lee Justin Y. , Styczynski Mark P. 
Published: May 2021

AbstractMotivationAs the large-scale study of metabolites and a direct readout of a system’s metabolic state, metabolomics has significant appeal as a source of information for many metabolic modelling platforms and other metabolic analysis tools. However, metabolomics data are typically reported in terms of relative abundances, which precluding use with tools where absolute concentrations are necessary. While chemical standards can be used to determine the absolute concentrations of metabolites, they are often time-consuming to run, expensive, or unavailable for many metabolites. A computational framework that can infer absolute concentrations without the use of chemical standards would be highly beneficial to the metabolomics community.ResultsWe have developed and characterized MetaboPAC, a computational strategy that leverages the mass balances of a system to infer absolute concentrations in metabolomics datasets. MetaboPAC uses a kinetic equations approach and an optimization approach to predict the most likely response factors that describe the relationship between absolute concentrations and their relative abundances. We determined that MetaboPAC performed significantly better than the other approaches assessed on noiseless data when at least 60% of kinetic equations are known a priori. Under the most realistic conditions (low sampling frequency, high noise data), MetaboPAC significantly outperformed other methods in the majority of cases when 100% of the kinetic equations were known. For metabolomics datasets extracted from systems that are well-studied and have partially known kinetic structures, MetaboPAC can provide valuable insight about their absolute concentration profiles.
Microinductor-Fused Atomic Force Microscopy Cantilevers for Dynamic Imaging and Multimodal Manipulation
Authors: Mousoulis Charilaos , Xu Xin , Wilson Robert L. , Chado Garrett , Wahlquist Joseph , Stoykovich Mark P. , Ferguson Virginia L. , Ziaie Babak , Neu Corey P. 
Published: May 2021

ABSTRACTRecent advances in atomic force microscopy (AFM) imaging and force spectroscopy have demonstrated improvements in rapid acquisition of quantitative data for applications in materials science, surface characterization, and biology. However, conventional AFM technology is limited in detection sensitivity and the ability to excite at off-resonance frequencies restricting broad utility of the technology. Here we demonstrate new AFM cantilevers fabricated with a planar microcoil at the tip region, which can be used to generate or sense highly-localized magnetic fields. Torsion/bending actuation of the cantilevers is accomplished with simple experimental configurations, enabling quantitative and simultaneous mapping of both stiffness and friction at the sample surface with more than one order of magnitude improvement in compositional contrast. Our method is compatible with commercial AFM systems, allowing us to clearly resolve small stiffness and friction variations in copolymer and biological samples that were difficult to detect by conventional AFM methods. In combination with fluorescence microscopy, we also generated localized fields to selectively stimulate and monitor structural changes in viable cells with nm-scale detail. Hybrid AFM cantilevers may be useful to characterize a broad range of complex material surfaces, in addition to combined physical and chemical analyses of single cells and biological microenvironments.
Sex Differences in the Incidence and Risk of Ankle-Foot Complex Stress Fractures Among U.S. Military Personnel
Authors: MacGregor Andrew J. , Fogleman Sarah A. , Dougherty Amber L. , Ryans Camille P. , Janney Cory F. , Fraser John J. 
Published: May 2021

AbstractBackgroundThe objective of this study was to evaluate sex differences in the incidence and risk of ankle-foot complex (AFC) stress fractures among U.S. military personnel, which could assist in developing management strategies as females assume a greater role in U.S. military operations.MethodsThe Defense Medical Epidemiological Database was used to identify all diagnosed AFC stress fractures in military personnel from 2006 to 2015. Cumulative incidence of AFC stress fractures was calculated and compared by year, service branch, and military rank. Sex differences in the risk of AFC stress fractures by occupation were examined, and integrated (i.e., male and female) occupations were compared with non-integrated (i.e., male-only) occupations.ResultsA total of 43,990 AFC stress fractures were identified. The overall incidence rate was 2.76 per 1,000 person-years for males and 5.78 per 1,000 person-years for females. Females consistently had higher incidence of AFC stress fractures across all subgroups, particularly among enlisted personnel. Female enlisted service members had the highest risk of AFC stress fractures in aviation [relative risk (RR) = 5.74; 95% confidence interval [CI] 4.80–6.87] and artillery/gunnery (RR = 5.15; 95% CI 4.62–5.75) occupations. Females in integrated occupations had significantly higher rates of AFC stress fractures than males in both integrated and non-integrated occupations (i.e., special forces, infantry, and mechanized/armor).ConclusionsFemales in the U.S. military have a higher risk of AFC stress fractures than males. As integration of females into previously sex-restricted occupations continues, focused prevention efforts may be needed to reduce injury burden and maximize medical readiness.
Hydroxychloroquine For Prophylaxis Of COVID-19 In Health Workers: A Randomized Clinical Trial
Authors: Rojas-Serrano Jorge , Thirion-Romero Angelica Margarita Portillo-Vásquez , Vázquez-Pérez Joel , Ramírez-Venegas Fidencio Mejía-Nepomuceno Alejandra , Pérez-Kawabe Karla Midori , Pérez-Padilla Rogelio 
Published: May 2021

SUMMARYHealth care workers are at high risk of being infected with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV2). Our aim is to evaluate the efficacy and safety of hydroxychloroquine (HCQ) for prophylaxis of COVID19 in health personnel exposed to patients infected by SARS-COV-2.MethodsDouble-blind randomized, placebo-controlled single center clinical trial. Included subjects were health care workers caring for severe COVD19 patients. Main outcome was time to symptomatic SARS-CoV2 infection.Results127 subjects with a confirmed baseline negative RT-PCR SARS-CoV2 test were included in the trial, 62 assigned to HCQ and 65 to placebo. One subject (1.6%) in the HCQ group and 6 (9,2%) subjects in the placebo group developed COVID-19. (Log Rank test p = 0.09). No severe COVID19 cases were observed. The study was suspended because of a refusal to participate and losses to follow up after several trials reported lack of effectiveness of hydroxychloroquine in hospitalized patients with COVID-19.CONCLUSIONAlthough the number of symptomatic infections in health personnel was lower in the HCQ group, the difference was not statistically significant. The trial is underpowered due to the failure to complete the estimated sample size.
Evaluation of SARS-CoV-2 rapid antigen diagnostic tests for saliva samples
Authors: Hagbom Marie , Carmona-Vicente Noelia , Sharma Sumit , Olsson Henrik , Jämtberg Mikael , Nilsdotter-Augustinsson Åsa , Sjöwall Johanna , Nordgren Johan 
Published: May 2021

AbstractBackgroundThe COVID-19 pandemic has highlighted the need for rapid, cost effective and easy-to-use diagnostic tools for SARS-CoV-2 rapid antigen detection (RAD) for use in point of care settings or as self-tests, to limit disease transmission. Using saliva samples would further greatly facilitate sample collection, diagnostic feasibility, and mass screening.ObjectiveWe tested two rapid antigen immunochromatographic tests designed for detection of SARS-CoV-2 in saliva: Rapid Response™ COVID-19 Antigen Rapid Test Cassette for oral fluids (Rapid Response) and DIAGNOS™ COVID-19 Antigen Saliva Test (DIAGNOS). Evaluation of detection limit was performed with purified SARS-CoV-2 nucleocapsid protein and titrated live SARS-CoV-2 virus and compared to Abbott Panbio™ COVID-19 Ag Rapid Test (Panbio) designed for nasopharyngeal samples. Sensitivity and specificity were further evaluated on RT-qPCR positive and negative saliva samples from individuals hospitalized with COVID-19 (n=34); and asymptomatic health care personnel (n=20).ResultsThe limit of detection of the saliva test from DIAGNOS was comparable with the Panbio test and showed higher sensitivity than Rapid Response for both nucleocapsid protein and diluted live viruses. DIAGNOS and Rapid Response further detected seven (47%) and five (33%), respectively, of the 15 RT-qPCR positive saliva samples in individuals hospitalized with COVID-19. Of the 39 RT-qPCR negative samples, all were negative with both tests (specificity 100%; 95% c.i. 0.91-1.00). Only one of the RT-qPCR positive saliva samples (Ct 21.6) contained infectious virus as determined by cell culture and was also positive using the saliva RADs.ConclusionThe results show that the DIAGNOS test exhibit a similar limit of detection as the Panbio RAD and may be an important and easy-to-use saliva RAD complement to detect infectious individuals.
CovidExpress: an interactive portal for intuitive investigation on SARS-CoV-2 related transcriptomes
Authors: Djekidel Mohamed Nadhir , Rosikiewicz Wojciech , Peng Jamy C. , Kanneganti Thirumala-Devi , Hui Yawei , Jin Hongjian , Hedges Dale , Schreiner Patrick , Fan Yiping , Wu Gang , Xu Beisi 
Published: May 2021

ABSTRACTInfection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in humans could cause coronavirus disease 2019 (COVID-19). Since its first discovery in Dec 2019, SARS-CoV-2 has become a global pandemic and caused 3.3 million direct/indirect deaths (2021 May). Amongst the scientific community’s response to COVID-19, data sharing has emerged as an essential aspect of the combat against SARS-CoV-2. Despite the ever-growing studies about SARS-CoV-2 and COVID-19, to date, only a few databases were curated to enable access to gene expression data. Furthermore, these databases curated only a small set of data and do not provide easy access for investigators without computational skills to perform analyses. To fill this gap and advance open-access to the growing gene expression data on this deadly virus, we collected about 1,500 human bulk RNA-seq datasets from publicly available resources, developed a database and visualization tool, named CovidExpress (https://stjudecab.github.io/covidexpress). This open access database will allow research investigators to examine the gene expression in various tissues, cell lines, and their response to SARS-CoV-2 under different experimental conditions, accelerating the understanding of the etiology of this disease to inform the drug and vaccine development. Our integrative analysis of this big dataset highlights a set of commonly regulated genes in SARS-CoV-2 infected lung and Rhinovirus infected nasal tissues, including OASL that were under-studied in COVID-19 related reports. Our results also suggested a potential FURIN positive feedback loop that might explain the evolutional advantage of SARS-CoV-2.
The Spike Proteins of SARS-CoV-2 B.1.617 and B.1.618 Variants Identified in India Provide Partial Resistance to Vaccine-elicited and Therapeutic Monoclonal Antibodies
Authors: Tada Takuya , Zhou Hao , Dcosta Belinda M. , Samanovic Marie I. , Mulligan Mark J. , Landau Nathaniel R. 
Published: May 2021

AbstractHighly transmissible SARS-CoV-2 variants recently identified in India designated B.1.617 and B.1.618 have mutations within the spike protein that may contribute to their increased transmissibility and that could potentially result in re-infection or resistance to vaccine-elicited antibody. B.1.617 encodes a spike protein with mutations L452R, E484Q, D614G and P681R while the B.1.618 spike has mutations Δ145-146, E484K and D614G. We generated lentiviruses pseudotyped by the variant proteins and determined their resistance to neutralization by convalescent sera, vaccine-elicited antibodies and therapeutic monoclonal antibodies. Viruses with B.1.617 and B.1.618 spike were neutralized with a 2-5-fold decrease in titer by convalescent sera and vaccine-elicited antibodies. The E484Q and E484K versions were neutralized with a 2-4-fold decrease in titer. Virus with the B.1.617 spike protein was neutralized with a 4.7-fold decrease in titer by the Regeneron monoclonal antibody cocktail as a result of the L452R mutation. The modest neutralization resistance of the variant spike proteins to vaccine elicited antibody suggests that current vaccines will remain protective against the B.1.617 and B.1.618 variants.
Fatal breakthrough infection after anti-BCMA CAR-T therapy highlights suboptimal immune response to SARS-CoV-2 vaccination in myeloma patients
Authors: Aleman Adolfo , Van Oekelen Oliver , Upadhyaya Bhaskar , Agte Sarita , Kappes Katerina , Beach Katherine , Srivastava Komal , Gleason Charles R. ,   PVI study group, Wang Bo , Mouhieddine Tarek H. , Tuballes Kevin , Geanon Daniel , Khan Zenab , Gonzalez-Reiche Ana S. , van Bakel Harm , Simons Nicole W. , Mouskas Konstantinos , Charney Alexander W. , Rahman Adeeb , Kim-Schulze Seunghee , Sordillo Emilia M. , Krammer Florian , Cordon-Cardo Carlos , Bhardwaj Nina , Gnjatic Sacha , Merad Miriam , Brown Brian D. , Sanchez Larysa , Chari Ajai , Jagannath Sundar , Simon Viviana , Wajnberg Ania , Parekh Samir 
Published: May 2021

SUMMARYSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines are highly effective in healthy individuals. Patients with multiple myeloma (MM) are immunocompromised due to defects in humoral and cellular immunity as well as immunosuppressive therapies. The efficacy after two doses of SARS-CoV-2 mRNA vaccination in MM patients is currently unknown. Here, we report the case of a MM patient who developed a fatal SARS-CoV-2 infection after full vaccination while in remission after B cell maturation antigen (BCMA)-targeted chimeric antigen receptor (CAR)-T treatment. We show that the patient failed to generate antibodies or SARS-CoV-2-specific B and T cell responses, highlighting the continued risk of severe coronavirus disease 2019 (COVID-19) in vaccine non-responders. In the largest cohort of vaccinated MM patients to date, we demonstrate that 15.9% lack SARS-CoV-2 spike antibody response more than 10 days after the second mRNA vaccine dose. The patients actively receiving MM treatment, especially on regimens containing anti-CD38 and anti-BCMA, have lower antibody responses compared to healthy controls. Thus, it is of critical importance to monitor this patient population for serological responses. Non-responders may benefit from ongoing public health measures and from urgent study of prophylactic treatments to prevent SARS-CoV-2 infection.