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Abstract Background Hazardous noise exposure is an important health concern in many workplaces and is one of the most common work-related injuries in the United States. Dental professionals are frequently exposed to high levels of occupational noise in their daily work environment. This noise is generated by various dental handpieces such as drills, suctions, and ultrasonic scalers. Prolonged exposure to such noise levels is known to have adverse effects on hearing health. Despite the prevalence of occupational noise in dentistry, there is a paucity of research specifically examining the prevalence of hearing loss and tinnitus in dental professionals. Methods To evaluate the prevalence of hearing loss and tinnitus, data were collected from 60 dental professionals, including participant demographics and audiometric thresholds. Thresholds were compared to the age- and sex-based reference ranges from the International Standards Organization (ISO 7029:2017). Results Results showed that 15–25% of males and 13–18% of females had hearing thresholds that exceeded 95th percentile limits based on the ISO normative age- and sex-distributions. Tinnitus was reported in 40% of the participants. Conclusion This study is the first to examine the characteristics and prevalence of auditory dysfunctions in dental professionals compared to the ISO normative age and sex distributions of hearing status. Findings from this study highlight the need for increasing the awareness of occupational noise hazards among dental professionals and the importance of routine audiological monitoring.

Abstract Objective Schools play an essential role in providing mental health care for adolescents. School closures during COVID-19, as well as re-opening to remote-only instruction in Fall 2020, may indirectly affect the utilization of emergency psychiatric care. We examine COVID-19-related changes in emergency psychiatric care among youth during the school closure and after school reopening (with remote instruction). Methods We use Box-Jenkins interrupted time series methods to analyze psychiatric emergency department (ED) visits among patients 10–19 years at LAC + USC Medical Center (LAC + USC) between January 5th, 2018, and December 31st, 2020. We control for the 1st societal shutdown in LA County (i.e., the nine weeks from March 13 to May 14, 2020) when analyzing the potential “return to remote school” shock. Results Youth psychiatric ED visits fell by 15.3 per week during the Spring 2020 school closure (p

Background: The impact of socioeconomic distress on readmission rates following cardiac surgery has not been studied. We hypothesized that patients living in distressed communities would have a higher 30-day readmission rate after cardiac surgery compared to those living in less distressed communities. Methods: Patients undergoing isolated coronary artery bypass grafting (CABG) between 2016 and 2023 within a regional collaborative were identified. The Distressed Communities Index (DCI) and Area Deprivation Index (ADI) were used to measure socioeconomic distress. Two logistic regression models were performed to evaluate 30-day readmission rates: one incorporating ADI and the other including DCI. Models were adjusted for the Society of Thoracic Surgeons (STS) Predicted Risk of Mortality (PROM) score, postoperative complications, length of stay (LOS), year of surgery, and discharge disposition. Results: A total of 16,369 patients were included, of whom 10% were readmitted within 30 days of discharge. Readmitted patients were more likely to be female (32% vs 23.3%) and to develop postoperative complications (47% vs 35%) and less likely to be discharged to home (70.6% vs 83.5%; P

Abstract Myelin regeneration (remyelination) is essential to prevent neurodegeneration in demyelinating diseases such as Multiple Sclerosis, however, its efficiency declines with age. Regulatory T cells (Treg) recently emerged as critical players in tissue regeneration, including remyelination. However, the effect of ageing on Treg-mediated regenerative processes is poorly understood. Here, we show that expansion of aged Treg does not rescue age-associated remyelination impairment due to an intrinsically diminished capacity of aged Treg to promote oligodendrocyte differentiation and myelination in male and female mice. This decline in regenerative Treg functions can be rescued by a young environment. We identified Melanoma Cell Adhesion Molecule 1 (MCAM1) and Integrin alpha 2 (ITGA2) as candidates of Treg-mediated oligodendrocyte differentiation that decrease with age. Our findings demonstrate that ageing limits the neuroregenerative capacity of Treg, likely limiting their remyelinating therapeutic potential in aged patients, and describe two mechanisms implicated in Treg-driven remyelination that may be targetable to overcome this limitation.

This report evaluates the pulsed breakdown performance of C4F7N under a 6.8 kV/ns voltage excitation. The pulsed dielectric strength of C4F7N is compared to SF6 in the same experimental setup, and it is found that C4F7N concentrations of 50% or greater are required to achieve a dielectric strength greater than or equal to SF6. Pure C4F7N demonstrated higher electric field hold-off for longer time periods and less statistical variance under pulsed conditions when compared to SF6. Mixtures of 50%C4F7N with N2 or CO2 as buffer gases showed no appreciable difference in pulsed dielectric strength.

Urban greenspaces are vital refugia for insect biodiversity, but seasonal fluctuation responses of insect taxa to urbanisation and local attributes of urban greenspaces are not well known. Regions with mild temperate climates and winter-flowering plants have active winter pollinators that are often neglected. A thorough knowledge of the seasonally fluctuating ecological needs of insects is essential for adequate insect-friendly greenspace management. Hover flies are cosmopolitan inhabitants of urban greenspaces where they provide multiple critical ecosystem services such as pollination and pest control. Our study uses a multi-scale approach to determine the seasonal effects of urbanisation on hover fly richness, abundance, and assemblages in urban greenspaces. We selected 30 sites along an urbanisation gradient (as measured by human population density) in Sydney, Australia, and sampled each site over a year across seasons. We found that hover fly species richness was higher in winter and spring than in summer, while abundance was highest in winter and lowest in summer. Our results also show that a combination urbanisation and local attributes of urban greenspaces (flower richness, flower abundance, human population density, and proportion of native flowers) combined to affect hover fly species richness and abundance in seasonally dependant ways. Hover flies are especially abundant and diverse during winter- a time of the year when other native floral visitors are less active. Thus, hover flies may be important pollinators of the large community of winter-flowering plants in Australia. Urban greenspaces can be made more hospitable to hover flies by implementing simple management initiatives, such as complementing native floral resources with non-native flowers in periods of scarcity.

Peanut is a critical food crop worldwide, and the development of high-throughput phenotyping techniques is essential for enhancing the crop’s genetic gain rate. Given the obvious challenges of directly estimating peanut yields through remote sensing, an approach that utilizes above-ground phenotypes to estimate underground yield is necessary. To that end, this study leveraged unmanned aerial vehicles (UAVs) for high-throughput phenotyping of surface traits in peanut. Using a diverse set of peanut germplasm planted in 2021 and 2022, UAV flight missions were repeatedly conducted to capture image data that were used to construct high-resolution multitemporal sigmoidal growth curves based on apparent characteristics, such as canopy cover and canopy height. Latent phenotypes extracted from these growth curves and their first derivatives informed the development of advanced machine learning models, specifically random forest and eXtreme Gradient Boosting (XGBoost), to estimate yield in the peanut plots. The random forest model exhibited exceptional predictive accuracy (R2 = 0.93), while XGBoost was also reasonably effective (R2 = 0.88). When using confusion matrices to evaluate the classification abilities of each model, the two models proved valuable in a breeding pipeline, particularly for filtering out underperforming genotypes. In addition, the random forest model excelled in identifying top-performing material while minimizing Type I and Type II errors. Overall, these findings underscore the potential of machine learning models, especially random forests and XGBoost, in predicting peanut yield and improving the efficiency of peanut breeding programs.

Introduction Around the world, many organisations are working on ways to increase the use, sharing, and reuse of person-level data for research, evaluation, planning, and innovation while ensuring that data are secure and privacy is protected. As a contribution to broader efforts to improve data governance and management, in 2020 members of our team published 12 minimum specification essential requirements (min specs) to provide practical guidance for organisations establishing or operating data trusts and other forms of data infrastructure. Approach and Aims We convened an international team, consisting mostly of participants from Canada and the United States of America, to test and refine the original 12 min specs. Twenty-three (23) data-focused organisations and initiatives recorded the various ways they address the min specs. Sub-teams analysed the results, used the findings to make improvements to the min specs, and identified materials to support organisations/initiatives in addressing the min specs. Results Analyses and discussion led to an updated set of 15 min specs covering five categories: one min spec for Legal, five for Governance, four for Management, two for Data Users, and three for Stakeholder & Public Engagement. Multiple changes were made to make the min specs language more technically complete and precise. The updated set of 15 min specs has been integrated into a Canadian national standard that, to our knowledge, is the first to include requirements for public engagement and Indigenous Data Sovereignty. Conclusions The testing and refinement of the min specs led to significant additions and improvements. The min specs helped the 23 organisations/initiatives involved in this project communicate and compare how they achieve responsible and trustworthy data governance and management. By extension, the min specs, and the Canadian national standard based on them, are likely to be useful for other data-focused organisations and initiatives.

Abstract Background Undocumented immigrants face barriers to health care access, which may have been exacerbated during the early days of the COVID-19 pandemic. We test whether undocumented immigrants in Los Angeles County accessed COVID-19 related medical care by examining their Emergency Department (ED) patterns through high and low periods of COVID-19 infection. If undocumented immigrants were underutilizing or foregoing health care, we expect null or weaker associations between COVID-19 cases and COVID-19 related ED visits relative to Medi-Cal patients. Methods We analyzed all ED visits to the Los Angeles County + University of Southern California (LAC + USC) Medical Center between March - December 2020 (n = 85,387). We conducted logistic regressions with Los Angeles County weekly COVID-19 case counts as our main independent variable and an interaction between case counts and immigration status, stratified by age (over and under 65 years). Results We found that undocumented immigrants under 65 years old had a higher odds for a COVID-19 related ED visit compared to Medi-Cal patients and that both undocumented and Medi-Cal patients had higher odds of a COVID-19 related ED visit as COVID-19 cases in Los Angeles County increased. For patients over 65 years, Medi-Cal patients actually had a weaker association between ED visits and county COVID-19 counts; as COVID-19 case counts rose, the odds of a COVID-19 related ED visit increased for the undocumented patients. Conclusion While the overall likelihood of undocumented patients having a COVID-19 related ED visit varies compared to Medi-Cal patients - for younger patients, the odds is higher; for older patients, the odds is lower - it does not appear that undocumented patients underutilized the ED during the early COVID-19 pandemic relative to Medi-Cal patients. The ED may be a viable source of contact for this high-risk population for future outreach.

The pain of occipital neuralgia (ON) is thought to be secondary to trauma or injury to the occipital nerve at any point along the course of the nerve. ON may also be caused by an infectious process (herpes zoster) or compression of the nerve. The patient, in this case, presented to our clinic with complaints of occipital pain and rash and swelling of the right lower jaw. One week before presenting to our clinic, the patient developed severe pain in the first division of the trigeminal region with erythema and vesicles. A blood test showed a remarkably high antibody titer for varicella–zoster virus (VZV). The patient was prescribed oral valacyclovir (Valtrex®) (3000 mg/day), which resulted in the complete remission of the rash and blisters in the occipital region. This highlights the importance of considering neuroanatomy of the trigeminal region and cervical nerve.

Background/purpose: Burning mouth syndrome (BMS) is a chronic condition presenting as intraoral burning or dysesthesia, with a high preponderance in menopausal women. This study aimed to examine the association between somatosensory dysfunction and BMS in premenopausal, early postmenopausal, and late postmenopausal patients, using a standardized Quantitative Sensory Testing (QST) protocol, and to determine the predictive value of thermal or mechanical perception by QST for detecting BMS. Materials and methods: An observational case–control study was performed with 36 female participants with BMS (12 premenopausal, 10 early postmenopausal, and 14 late postmenopausal) and 42 age- and sex-matched healthy volunteers (21 premenopausal, 10 early postmenopausal, and 11 late postmenopausal). Neurophysiological tests were used to evaluate somatosensory dysfunction at the tongue. Results: Z-score in the late postmenopausal BMS group revealed a gain of function for the cold pain threshold and heat pain threshold (Z = 2.08 and 3.38, respectively). In the multiple regression analysis with the Visual Analog Scale as the dependent variable, the vibration detection threshold predicted the severity of burning mouth sensation in the premenopausal group. Conclusion: Late postmenopausal patients with BMS showed an increased response of the tongue to noxious thermal stimuli. This supports the theory that changes in sex hormones may affect trigeminal somatosensory function, particularly during the late postmenopausal stage in patients with BMS.

Orofacial pain is a frequent chief complaint of many systemic disorders. A primary cough headache may mimic the clinical symptoms of a temporomandibular disorder (TMD) or may be associated with TMDs. Case report: A 52-year-old man presented with a 1-year history of TMD symptoms with clicking. He presented with the chief complaint of a sudden and severe headache when coughing, sneezing, or crouching. Comprehensive intra- and extra-oral examinations were performed, which revealed myofascial pain involving the right masseter and temporalis muscles, disc displacement with reduction in the right temporomandibular joint, and headache attributed to TMD, but no severe headaches appeared in the cough-induced test at the first visit. Initially, we advised the patient to minimize activities that require jaw function (e.g., chewing), avoid jaw parafunction (e.g., bruxism), and to perform at-home jaw exercises to stretch the jaw muscles. The patient’s symptoms reduced by more than half after the TMD home care and physiotherapy. He was then treated with 75 mg of indomethacin per day, which eliminated his headache. The patient was then referred to a headache specialist, who diagnosed primary cough headache.

Innovative, responsible data use is a critical need in the global response to the coronavirus disease-2019 (COVID-19) pandemic. Yet potentially impactful data are often unavailable to those who could utilize it, particularly in data-poor settings, posing a serious barrier to effective pandemic mitigation. Data challenges, a public call-to-action for innovative data use projects, can identify and address these specific barriers. To understand gaps and progress relevant to effective data use in this context, this study thematically analyses three sets of qualitative data focused on/based in low/middle-income countries: (a) a survey of innovators responding to a data challenge, (b) a survey of organizers of data challenges, and (c) a focus group discussion with professionals using COVID-19 data for evidence-based decision-making. Data quality and accessibility and human resources/institutional capacity were frequently reported limitations to effective data use among innovators. New fit-for-purpose tools and the expansion of partnerships were the most frequently noted areas of progress. Discussion participants identified building capacity for external/national actors to understand the needs of local communities can address a lack of partnerships while de-siloing information. A synthesis of themes demonstrated that gaps, progress, and needs commonly identified by these groups are relevant beyond COVID-19, highlighting the importance of a healthy data ecosystem to address emerging threats. This is supported by data holders prioritizing the availability and accessibility of their data without causing harm; funders and policymakers committed to integrating innovations with existing physical, data, and policy infrastructure; and innovators designing sustainable, multi-use solutions based on principles of good data governance.

The COVID-19 pandemic response has shown how vaccine platform technologies can be used to rapidly and effectively counteract a novel emerging infectious disease. The speed of development for mRNA and vector-based vaccines outpaced those of subunit vaccines, however, subunit vaccines can offer advantages in terms of safety and stability. Here we describe a subunit vaccine platform technology, the molecular clamp, in application to four viruses from divergent taxonomic families: Middle Eastern respiratory syndrome coronavirus (MERS-CoV), Ebola virus (EBOV), Lassa virus (LASV) and Nipah virus (NiV). The clamp streamlines subunit antigen production by both stabilising the immunologically important prefusion epitopes of trimeric viral fusion proteins while enabling purification without target-specific reagents by acting as an affinity tag. Conformations for each viral antigen were confirmed by monoclonal antibody binding, size exclusion chromatography and electron microscopy. Notably, all four antigens tested remained stable over four weeks of incubation at 40°C. Of the four vaccines tested, a neutralising immune response was stimulated by clamp stabilised MERS-CoV spike, EBOV glycoprotein and NiV fusion protein. Only the clamp stabilised LASV glycoprotein precursor failed to elicit virus neutralising antibodies. MERS-CoV and EBOV vaccine candidates were both tested in animal models and found to provide protection against viral challenge.

As a society, we need to become more sophisticated in assessing and addressing data asymmetries—and their resulting political and economic power inequalities—particularly in the realm of open science, research, and development. This article seeks to start filling the analytical gap regarding data asymmetries globally, with a specific focus on the asymmetrical availability of privately-held data for open science, and a look at current efforts to address these data asymmetries. It provides a taxonomy of asymmetries, as well as both their societal and institutional impacts. Moreover, this contribution outlines a set of solutions that could provide a toolbox for open science practitioners and data demand-side actors that stand to benefit from increased access to data. The concept of data liquidity (and portability) is explored at length in connection with efforts to generate an ecosystem of responsible data exchanges. We also examine how data holders and demand-side actors are experimenting with new and emerging operational models and governance frameworks for purpose-driven, cross-sector data collaboratives that connect previously siloed datasets. Key solutions discussed include professionalizing and re-imagining data steward roles and functions (i.e., individuals or groups who are tasked with managing data and their ethical and responsible reuse within organizations). We present these solutions through case studies on notable efforts to address science data asymmetries. We examine these cases using a repurposable analytical framework that could inform future research. We conclude with recommended actions that could support the creation of an evidence base on work to address data asymmetries and unlock the public value of greater science data liquidity and responsible reuse.

Abstract Mobile phone data have been extensively used to study urban mobility. However, studies based on gender-disaggregated large-scale data are still lacking, limiting our understanding of gendered aspects of urban mobility and our ability to design policies for gender equality. Here we study urban mobility from a gendered perspective, combining commercial and open datasets for the city of Santiago, Chile. We analyze call detail records for a large cohort of anonymized mobile phone users and reveal a gender gap in mobility: women visit fewer unique locations than men, and distribute their time less equally among such locations. Mapping this mobility gap over administrative divisions, we observe that a wider gap is associated with lower income and lack of public and private transportation options. Our results uncover a complex interplay between gendered mobility patterns, socio-economic factors and urban affordances, calling for further research and providing insights for policymakers and urban planners.

Machine learning and artificial intelligence has been applied to other facets of structural mechanics and structural dynamics, mainly for structural optimization and structural reliability analysis, but have seen little use in surrogate modeling for structural time series prediction. The current research will focus on how data reduction tools (such as mathematical morphology) can be applied to dynamic structural data and can be used in conjunction with clustering methodologies as well as artificial neural networks (ANNs) to create a useful and highly computationally efficient dynamic model that can be used to make predictions on the acceleration response of a structural system. The current study utilizes training data developed from finite element modeling of a simple system that demonstrates a nonlinear behavior of interest (a change in the dynamic response with a change in loading magnitude), but the methodologies developed could be applied to other modeling or analysis schemes, test data, or in-situ measurements of a structure of interest. The results of the study show how mathematical morphology tools can reduce the dimensionality of time series data while still preserving important characteristics like natural frequency, and the use of ANNs shows promise as a surrogate model for dynamic response prediction.

We present the results from a coordinated XMM-Newton + NuSTAR observation of the Seyfert 1 galaxy ESO 511−G030. With this joint monitoring program, we conduct a detailed variability and spectral analysis. The source remained in a low flux and very stable state throughout the observation period, although there are slight fluctuations of flux over long timescales. The broadband (0.3–78 keV) spectrum shows the presence of a power-law continuum with a soft excess below 2 keV, a relatively narrow iron K α emission (∼6.4 keV), and an obvious cutoff at high energies. We find that the soft excess can be modeled by two different possible scenarios: a warm ( kT _e ∼ 0.19 keV) and optically thick ( τ = 18–25) Comptonizing corona or a relativistic reflection from a high-density ( $\mathrm{log}[{n}_{{\rm{e}}}/{\mathrm{cm}}^{-3}]=17.1\mbox{--}18.5$ ) inner disk. All models require a low temperature ( kT _e ∼ 13 keV) for the hot corona.

Secondary trigeminal neuralgia might be very rarely preceded by trigeminal neuropathic pain. The patient, in this case, presented with paroxysmal pain in the left mandible and numbness of the lower lip and tongue. Sensory testing of these areas revealed cold and heat hyperalgesia and mechanical hyposensitivity in the mandibular region. Magnetic resonance imaging showed a mass in the left cerebellopontine angle. The patient was prescribed systemic mirogabalin (2.5 mg/day), which provided some relief until the tumor was removed. The histopathological diagnosis was an epidermoid tumor. This article discusses the clinical characteristics and sensory testing findings that distinguish secondary trigeminal neuralgia from trigeminal neuropathic pain based on the International Classification of Orofacial Pain.

Abstract Background To systematically review and assess the in vivo effectiveness and safety of probiotics for prophylaxis and treating oral candidiasis. Methods A literature search for studies published in English until August 1, 2018 was conducted in the following databases: PubMed, EMBASE, Cochrane Library, and Web of Science. Randomized controlled clinical trials and experimental mouse animal model studies comparing probiotics (at any dosage and in any form) with control groups (placebo, blank control or other agents) and reporting outcomes of the prophylactic and therapeutic effects were considered for inclusion. A descriptive study and, potentially, a meta-analysis were planned. Results Six randomized controlled clinical trials and 5 controlled experiments of mouse animal models were included in the systematic review. Four randomized controlled clinical trials comparing a probiotics group with a placebo/blank control group in 480 elderly and denture wearers were included in the meta-analysis. The overall combined odds ratio of the (random effects) meta-analysis was 0.24 (95% CI =0.09–0.63, P

Abstract We review the current state of quality assurance in laboratories of the five Central Asia Republics (CARs), focusing on laboratory equipment, and compare quality assurance approaches with CLSI standards. The laboratories of the CARs faced exceptional challenges including highly-structured laboratory systems that retain centralized and outmoded Soviet-era approaches to quality assurance, considerably jeopardizing the validity of laboratory tests. The relative isolation of the CARs, based on geography and almost exclusive use of the Russian language, further hamper change. CARs must make high-level government decisions to widely implement quality assurance programs within their laboratory systems, within which approaches to the management of laboratory equipment will be a prominent part.

Used in many industrial applications, centrifugal pumps have optimal operating criteria specified at design. These criteria may not be precisely adhered to during operation which will ultimately reduce the life of the asset. Operators would therefore benefit from anticipating how often the design point is deviated from and hence how much asset degradation results. For centrifugal pumps, a novel set of covariates were proposed in this paper which formally partition observed operating zones with an Empirical Bivariate Quantile Partitioned distribution. This captured the dependency relation between operating parameters across plant configurations to predict the component wear that results from particular settings. The effectiveness of this was demonstrated through an operational case study in civil nuclear generation feedwater pumps where corroboration with bearing movements provides an indicator of plant wear. Such a technique is envisaged to inform operators of optimal plant configuration from multiple possibilities in advance of undertaking them.

Abstract Objectives Efforts to develop and deploy effective vaccines against severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) continue at pace. Here, we describe rational antigen design through to manufacturability and vaccine efficacy of a prefusion‐stabilised spike (S) protein, Sclamp, in combination with the licensed adjuvant MF59 ‘MF59C.1’ (Seqirus, Parkville, Australia). Methods A panel recombinant Sclamp proteins were produced in Chinese hamster ovary and screened in vitro to select a lead vaccine candidate. The structure of this antigen was determined by cryo‐electron microscopy and assessed in mouse immunogenicity studies, hamster challenge studies and safety and toxicology studies in rat. Results In mice, the Sclamp vaccine elicits high levels of neutralising antibodies, as well as broadly reactive and polyfunctional S‐specific CD4+ and cytotoxic CD8+ T cells in vivo. In the Syrian hamster challenge model (n = 70), vaccination results in reduced viral load within the lung, protection from pulmonary disease and decreased viral shedding in daily throat swabs which correlated strongly with the neutralising antibody level. Conclusion The SARS‐CoV‐2 Sclamp vaccine candidate is compatible with large‐scale commercial manufacture, stable at 2–8°C. When formulated with MF59 adjuvant, it elicits neutralising antibodies and T‐cell responses and provides protection in animal challenge models.

Abstract One of the unmet clinical needs in demyelinating diseases such as Multiple Sclerosis (MS) is to provide therapies that actively enhance the process of myelin regeneration (remyelination) in the central nervous system (CNS). Oligodendrocytes, the myelinating cells of the CNS, play a central role in remyelination and originate from oligodendrocyte progenitor cells (OPCs). We recently showed that depletion of regulatory T cells (Treg) impairs remyelination in vivo, and that Treg-secreted factors directly enhance oligodendrocyte differentiation. Here we aim to further characterize the dynamics of Treg-enhanced oligodendrocyte differentiation as well as elucidate the cellular components of a murine mixed neuron-glia model. Murine mixed neuron-glia cultures were generated from P2–7 C57BL/6 mice and characterized for percentage of neuronal and glial cell populations prior to treatment at 7 days in vitro (div) as well as after treatment with Treg-conditioned media at multiple timepoints up to 12 div. Mixed neuron-glia cultures consisted of approximately 30% oligodendroglial lineage cells, 20% neurons and 10% microglia. Furthermore, a full layer of astrocytes, that could not be quantified, was present. Treatment with Treg-conditioned media enhanced the proportion of MBP+ oligodendrocytes and decreased the proportion of PDGFRα+ OPCs, but did not affect OPC proliferation or survival. Treg-enhanced oligodendrocyte differentiation was not caused by Treg polarizing factors, was dependent on the number of activation cycles Treg underwent and was robustly achieved by using 5% conditioned media. These studies provide in-depth characterization of a murine mixed neuron-glia model as well as further insights into the dynamics of Treg-enhanced oligodendrocyte differentiation.

Nearly a century after rheumatic fever (RF) and rheumatic heart disease (RHD) was eradicated from the developed world, the disease remains endemic in many low- and middle-income countries (LMICs), with grim health and socioeconomic impacts. The neglect of RHD which persisted for a semi-centennial was further driven by competing infectious diseases, particularly the human immunodeficiency virus (HIV) pandemic. However, over the last two-decades, slowly at first but with building momentum, there has been a resurgence of interest in RF/RHD. In this narrative review, we present the advances that have been made in the RF/RHD continuum over the past two decades since the re-awakening of interest, with a more concise focus on the last decade’s achievements. Such primary advances include understanding the genetic predisposition to RHD, group A Streptococcus (GAS) vaccine development, and improved diagnostic strategies for GAS pharyngitis. Echocardiographic screening for RHD has been a major advance which has unearthed the prevailing high burden of RHD and the recent demonstration of benefit of secondary antibiotic prophylaxis on halting progression of latent RHD is a major step forward. Multiple befitting advances in tertiary management of RHD have also been realized. Finally, we summarize the research gaps and provide illumination on profitable future directions towards global eradication of RHD.

Nipah virus (NiV) and respiratory syncytial virus (RSV) possess two surface glycoproteins involved in cellular attachment and membrane fusion, both of which are potential targets for vaccines. The majority of vaccine development is focused on the attachment (G) protein of NiV, which is the immunodominant target. In contrast, the fusion (F) protein of RSV is the main target in vaccine development. Despite this, neutralising epitopes have been described in NiV F and RSV G, making them alternate targets for vaccine design. Through rational design, we have developed a vaccine strategy applicable to phylogenetically divergent NiV and RSV that comprises both the F and G proteins (FxG). In a mouse immunization model, we found that NiV FxG elicited an improved immune response capable of neutralising pseudotyped NiV and a NiV mutant that is able to escape neutralisation by two known F-specific antibodies. RSV FxG elicited an immune response against both F and G and was able to neutralise RSV; however, this was inferior to the immune response of F alone. Despite this, RSV FxG elicited a response against a known protective epitope within G that is conserved across RSV A and B subgroups, which may provide additional protection in vivo. We conclude that inclusion of F and G antigens within a single design provides a streamlined subunit vaccine strategy against both emerging and established pathogens, with the potential for broader protection against NiV.

Idiopathic condylar resorption (ICR) is a condition with no known cause, which manifests as progressive malocclusion, esthetic changes, and often pain. Cone-beam computed tomography and magnetic resonance imaging are the most valuable imaging methods for diagnosis and tracking, compared to the less complete and more distorted images provided by panoramic radiographs, and the higher radiation of 99mtechnetium-methylene diphosphonate. ICR has findings that overlap with osteoarthritis, inflammatory arthritis, physiologic resorption/remodeling, congenital disorders affecting the mandible, requiring thorough image analysis, physical examination, and history-taking. Correct diagnosis and determination of whether the ICR is active or inactive are essential when orthodontic or prosthodontic treatment is anticipated as active ICR can undo those treatments. Several treatments for ICR have been reported with the goals of either halting the progression of ICR or correcting the deformities that it caused. These treatments have varying degrees of success and adverse effects, but the rarity of the condition prevents any evidence-based recommendations.

Modulation of neural responses is frequently observed in the superior colliculus (SC), a retinorecipient midbrain structure that controls orienting and the localization of attention. Although behavioral contingencies that influence SC responses are well documented, the neural pathways and molecular mechanisms responsible for this modulation are not completely understood. Here, we illustrate a dopaminergic system that strongly impacts neural responses in the SC. After using RNA sequencing (RNA-seq) to detail the transcriptome of dopamine-related genes in the SC, we show that D1 receptors are enriched in the superficial visual SC, while D2 receptors segregate to the intermediate multimodal/motor SC. Retrograde injections into the SC consistently label A13, a small dopamine cell group located in the zona incerta. We surmise that A13 mimics dopaminergic effects that we observed in SC slices, which suggests that dopamine in the SC may reduce the tendency of an animal to orient or attend to salient stimuli.

The use of aerial imagery in agriculture is increasing. Improvements in unmanned aerial systems (UASs) and the hardware and software used to analyze imagery are presenting new options for agricultural studies. One of the challenges associated with improving crop performance under water deficit conditions is the increased variability in the growth and development inherent in low water settings. The nature of plant growth and development under water deficits makes it difficult to monitor the response to environmental changes. Small field and plot-level experiments are often variable enough that averages of seasonal crop characteristics may be of limited value to the researcher. This variability leads to a desire to resolve fields on finer temporal and spatial scales. While UAS imagery provides an ability to monitor the crop on a useful temporal scale, the spatial scale is still difficult to resolve. In this study, an automated computer software framework was developed to facilitate resolving field and plot-level crop imagery to finer spatial resolutions. The method uses a Binary Large Object (BLOB)-based algorithm to automate the generation of areas of measurement (AOMs) as a tool for crop analysis. The use of the BLOB-based system is demonstrated in the analysis of plots of cotton grown in Lubbock, Texas, during the summer of 2018. The method allowed the creation and analysis of 1133 AOMs from the plots and the extraction of agronomic data that described plant growth and development.

Methanol has become a widely used and globally distributed product. Methanol is very important due to the current depletion of fossil fuels. Industrially, methanol produced from the catalytic reaction of synthetic gas composed of hydrogen, carbon monoxide, and carbon dioxide. Methanol production has brought great attention due to carbon dioxide as the main source of greenhouse gas emissions. Combined of reducing CO2 emissions and supplying an alternative fuel source has created the idea of a carbon neutral cycle called “the methanol economy”. The best catalyst for the methanol economy would show a high CO2 conversion and high selectivity for methanol production. This paper investigates research focused on catalyst development for efficient methanol synthesis from hydrogenation of carbon dioxide through added various supports and additives such as silica, zirconium, and palladium. Catalysts that displayed the highest activity included a zirconia and silicon-titanium oxide promoted Cu/Zn/Al2O3 catalyst. Alternative method of catalyst preparation, include the oxalate-gel, solid-state reaction, co-precipitation and combustion method also investigated. © 2013 by Authors, Published by BCREC Group. This is an open access article under the CC BY-SA License (https://creativecommons.org/licenses/by-sa/4.0)

Understanding how the brain captures transient experience and converts it into long lasting changes in neural circuits requires the identification and investigation of the specific ensembles of neurons that are responsible for the encoding of each experience. We have developed a Robust Activity Marking (RAM) system that allows for the identification and interrogation of ensembles of neurons. The RAM system provides unprecedented high sensitivity and selectivity through the use of an optimized synthetic activity-regulated promoter that is strongly induced by neuronal activity and a modified Tet-Off system that achieves improved temporal control. Due to its compact design, RAM can be packaged into a single adeno-associated virus (AAV), providing great versatility and ease of use, including application to mice, rats, flies, and potentially many other species. Cre-dependent RAM, CRAM, allows for the study of active ensembles of a specific cell type and anatomical connectivity, further expanding the RAM system’s versatility.

Recent studies show that the amplitude of cortical field potentials is modulated in the time domain by grasping kinematics. However, it is unknown if these low frequency modulations persist and contain enough information to decode grasp kinematics in macro-scale activity measured at the scalp via electroencephalography (EEG). Further, it is unclear as to whether joint angle velocities or movement synergies are the optimal kinematics spaces to decode. In this offline decoding study, we infer from human EEG, hand joint angular velocities as well as synergistic trajectories as subjects perform natural reach-to-grasp movements. Decoding accuracy, measured as the correlation coefficient (r) between the predicted and actual movement kinematics, was r = 0.49 ± 0.02 across fifteen hand joints. Across the first three kinematic synergies, decoding accuracies were r = 0.59 ± 0.04, 0.47 ± 0.06 and 0.32 ± 0.05. The spatial-temporal pattern of EEG channel recruitment showed early involvement of contralateral frontal-central scalp areas followed by later activation of central electrodes over primary sensorimotor cortical areas. Information content in EEG about the grasp type peaked at 250 ms after movement onset. The high decoding accuracies in this study are significant not only as evidence for time-domain modulation in macro-scale brain activity, but for the field of brain-machine interfaces as well. Our decoding strategy, which harnesses the neural ‘symphony’ as opposed to local members of the neural ensemble (as in intracranial approaches), may provide a means of extracting information about motor intent for grasping without the need for penetrating electrodes and suggests that it may be soon possible to develop non-invasive neural interfaces for the control of prosthetic limbs.

In addition to classic functions of facilitating hepatobiliary secretion and intestinal absorption of lipophilic nutrients, bile acids (BA) are also endocrine factors and regulate glucose and lipid metabolism. Recent data indicate that antiobesity bariatric procedures e.g. Roux-en-Y gastric bypass surgery (RYGB), which also remit diabetes, increase plasma BAs in humans, leading to the hypothesis that BAs may play a role in diabetes resolution following surgery. To investigate the effect of RYGB on BA physiology and its relationship with glucose homeostasis, we undertook RYGB and SHAM surgery in Zucker diabetic fatty (ZDF) and normoglycemic Sprague Dawley (SD) rats and measured plasma and fecal BA levels, as well as plasma glucose, insulin, Glucagon like peptide 1 (GLP-1) and Peptide YY (PYY), 2 days before and 3, 7, 14 and 28 days after surgery. RYGB decreased body weight and increased plasma GLP-1 in both SD and ZDF rats while decreasing plasma insulin and glucose in ZDF rats starting from the first week. Compared to SHAM groups, both SD-RYGB and ZDF-RYGB groups started to have increases in plasma total BAs in the second week, which might not contribute to early post-surgery metabolic changes. While there was no significant difference in fecal BA excretion between SD-RYGB and SD-SHAM groups, the ZDF-RYGB group had a transient 4.2-fold increase (P

Identifying patients at risk of a 30-day readmission can help providers design interventions, and provide targeted care to improve clinical effectiveness. This study developed a risk model to predict a 30-day inpatient hospital readmission for patients in Maine, across all payers, all diseases and all demographic groups.Our objective was to develop a model to determine the risk for inpatient hospital readmission within 30 days post discharge. All patients within the Maine Health Information Exchange (HIE) system were included. The model was retrospectively developed on inpatient encounters between January 1, 2012 to December 31, 2012 from 24 randomly chosen hospitals, and then prospectively validated on inpatient encounters from January 1, 2013 to December 31, 2013 using all HIE patients.A risk assessment tool partitioned the entire HIE population into subgroups that corresponded to probability of hospital readmission as determined by a corresponding positive predictive value (PPV). An overall model c-statistic of 0.72 was achieved. The total 30-day readmission rates in low (score of 0-30), intermediate (score of 30-70) and high (score of 70-100) risk groupings were 8.67%, 24.10% and 74.10%, respectively. A time to event analysis revealed the higher risk groups readmitted to a hospital earlier than the lower risk groups. Six high-risk patient subgroup patterns were revealed through unsupervised clustering. Our model was successfully integrated into the statewide HIE to identify patient readmission risk upon admission and daily during hospitalization or for 30 days subsequently, providing daily risk score updates.The risk model was validated as an effective tool for predicting 30-day readmissions for patients across all payer, disease and demographic groups within the Maine HIE. Exposing the key clinical, demographic and utilization profiles driving each patient's risk of readmission score may be useful to providers in developing individualized post discharge care plans.

Immunosenescence, the deterioration of immune system capability with age, may play a key role in mediating age-related declines in whole-organism performance, but the mechanisms that underpin immunosenescence are poorly understood. Biomedical research on humans and laboratory models has documented age and disease related declines in the telomere lengths of leukocytes ('immune cells'), stimulating interest their having a potentially general role in the emergence of immunosenescent phenotypes. However, it is unknown whether such observations generalise to the immune cell populations of wild vertebrates living under ecologically realistic conditions. Here we examine longitudinal changes in the mean telomere lengths of immune cells in wild European badgers (Meles meles). Our findings provide the first evidence of within-individual age-related declines in immune cell telomere lengths in a wild vertebrate. That the rate of age-related decline in telomere length appears to be steeper within individuals than at the overall population level raises the possibility that individuals with short immune cell telomeres and/or higher rates of immune cell telomere attrition may be selectively lost from this population. We also report evidence suggestive of associations between immune cell telomere length and bovine tuberculosis infection status, with individuals detected at the most advanced stage of infection tending to have shorter immune cell telomeres than disease positive individuals. While male European badgers are larger and show higher rates of annual mortality than females, we found no evidence of a sex difference in either mean telomere length or the average rate of within-individual telomere attrition with age. Our findings lend support to the view that age-related declines in the telomere lengths of immune cells may provide one potentially general mechanism underpinning age-related declines in immunocompetence in natural populations.

Among patients who are discharged from the Emergency Department (ED), about 3% return within 30 days. Revisits can be related to the nature of the disease, medical errors, and/or inadequate diagnoses and treatment during their initial ED visit. Identification of high-risk patient population can help device new strategies for improved ED care with reduced ED utilization.A decision tree based model with discriminant Electronic Medical Record (EMR) features was developed and validated, estimating patient ED 30 day revisit risk. A retrospective cohort of 293,461 ED encounters from HealthInfoNet (HIN), Maine's Health Information Exchange (HIE), between January 1, 2012 and December 31, 2012, was assembled with the associated patients' demographic information and one-year clinical histories before the discharge date as the inputs. To validate, a prospective cohort of 193,886 encounters between January 1, 2013 and June 30, 2013 was constructed. The c-statistics for the retrospective and prospective predictions were 0.710 and 0.704 respectively. Clinical resource utilization, including ED use, was analyzed as a function of the ED risk score. Cluster analysis of high-risk patients identified discrete sub-populations with distinctive demographic, clinical and resource utilization patterns.Our ED 30-day revisit model was prospectively validated on the Maine State HIN secure statewide data system. Future integration of our ED predictive analytics into the ED care work flow may lead to increased opportunities for targeted care intervention to reduce ED resource burden and overall healthcare expense, and improve outcomes.

Progressive supranuclear palsy (PSP) is a progressive, debilitating neurodegenerative disease of the Parkinson-plus family of syndromes. Unfortunately, there are no pharmacologic treatments for this condition, as most sufferers of the classic variant respond poorly to Parkinson medications such as levodopa. Zolpidem, a gamma aminobutyric acid (GABA) agonist specific to the α-1 receptor subtype, has been reported to show improvements in symptoms of PSP patients, including motor dysfunction, dysarthria, and ocular disturbances. We observed a 73-year-old woman with a six-year history of PSP, who, upon administration of a single 12.5 mg dose of sustained-release zolpidem, exhibited marked enhancements in speech, facial expressions, and fine motor skills for five hours. These results were reproduced upon subsequent clinic visits. In an effort to find a sustainable medication that maximized these beneficial effects while minimizing side effects and addressing some of her comorbid neuropsychological conditions, a trial of five other GABA receptor agonists was performed with the patient’s consent, while she and her caregivers were blinded to the specific medications. She and her caretakers subsequently reported improvements, especially visual, while on eszopiclone, and, to a lesser degree, temazepam and flurazepam.

Calcium and apatite granulations are demonstrated here to form in both human and fetal bovine serum in response to the simple addition of either calcium or phosphate, or a combination of both. These granulations are shown to represent precipitating complexes of protein and hydroxyapatite (HAP) that display marked pleomorphism, appearing as round, laminated particles, spindles, and films. These same complexes can be found in normal untreated serum, albeit at much lower amounts, and appear to result from the progressive binding of serum proteins with apatite until reaching saturation, upon which the mineralo-protein complexes precipitate. Chemically and morphologically, these complexes are virtually identical to the so-called nanobacteria (NB) implicated in numerous diseases and considered unusual for their small size, pleomorphism, and the presence of HAP. Like NB, serum granulations can seed particles upon transfer to serum-free medium, and their main protein constituents include albumin, complement components 3 and 4A, fetuin-A, and apolipoproteins A1 and B100, as well as other calcium and apatite binding proteins found in the serum. However, these serum mineralo-protein complexes are formed from the direct chemical binding of inorganic and organic phases, bypassing the need for any biological processes, including the long cultivation in cell culture conditions deemed necessary for the demonstration of NB. Thus, these serum granulations may result from physiologically inherent processes that become amplified with calcium phosphate loading or when subjected to culturing in medium. They may be viewed as simple mineralo-protein complexes formed from the deployment of calcification-inhibitory pathways used by the body to cope with excess calcium phosphate so as to prevent unwarranted calcification. Rather than representing novel pathophysiological mechanisms or exotic lifeforms, these results indicate that the entities described earlier as NB most likely originate from calcium and apatite binding factors in the serum, presumably calcification inhibitors, that upon saturation, form seeds for HAP deposition and growth. These calcium granulations are similar to those found in organisms throughout nature and may represent the products of more general calcium regulation pathways involved in the control of calcium storage, retrieval, tissue deposition, and disposal.

Putative living entities called nanobacteria (NB) are unusual for their small sizes (50-500 nm), pleomorphic nature, and accumulation of hydroxyapatite (HAP), and have been implicated in numerous diseases involving extraskeletal calcification. By adding precipitating ions to cell culture medium containing serum, mineral nanoparticles are generated that are morphologically and chemically identical to the so-called NB. These nanoparticles are shown here to be formed of amorphous mineral complexes containing calcium as well as other ions like carbonate, which then rapidly acquire phosphate, forming HAP. The main constituent proteins of serum-derived NB are albumin, fetuin-A, and apolipoprotein A1, but their involvement appears circumstantial since so-called NB from different body fluids harbor other proteins. Accordingly, by passage through various culture media, the protein composition of these particles can be modulated. Immunoblotting experiments reveal that antibodies deemed specific for NB react in fact with either albumin, fetuin-A, or both, indicating that previous studies using these reagents may have detected these serum proteins from the same as well as different species, with human tissue nanoparticles presumably absorbing bovine serum antigens from the culture medium. Both fetal bovine serum and human serum, used earlier by other investigators as sources of NB, paradoxically inhibit the formation of these entities, and this inhibition is trypsin-sensitive, indicating a role for proteins in this inhibitory process. Fetuin-A, and to a lesser degree albumin, inhibit nanoparticle formation, an inhibition that is overcome with time, ending with formation of the so-called NB. Together, these data demonstrate that NB are most likely formed by calcium or apatite crystallization inhibitors that are somehow overwhelmed by excess calcium or calcium phosphate found in culture medium or in body fluids, thereby becoming seeds for calcification. The structures described earlier as NB may thus represent remnants and by-products of physiological mechanisms used for calcium homeostasis, a concept which explains the vast body of NB literature as well as explains the true origin of NB as lifeless protein-mineralo entities with questionable role in pathogenesis.

Critical social media literacy—the ability to critically evaluate and interpret racist social media content (critical consumption) and to produce and disseminate antiracist social media content (critical prosumption)—may help counter the negative psychological consequences of online racism, including internalized racism. We examined whether critical social media literacy (critical consumption and prosumption) buffered the association between online racism and internalized racism. We conducted latent moderated structural equation modeling to analyze online convenience data from 338 racially minoritized emerging adults (Mage = 23.28; Asian, n = 96; Black, n = 108; Latine, n = 118). Greater exposure to online racism was associated with significantly higher levels of internalized racism; critical consumption weakened this association, while critical prosumption did not. Results suggested that critical social media literacy, particularly consumption—the intellectual basis and analytical skills to apprehend racist digital content—can be effective in mitigating the internalized racism linked to online racism among racially minoritized emerging adults. Implications include translating these findings into antiracist interventions to counter online racism and its deleterious behavioral health consequences. Public Significance Statement: Critical social media literacy can protect racially minoritized emerging adults from online racism, including by attenuating internalized racism—a correlate of numerous behavioral health outcomes. It is imperative to promote critical education that empowers racially minoritized individuals with the social media literacy needed to counteract the 21st-century cyberscape of racial hate and violence. [ABSTRACT FROM AUTHOR]