bluuebunny/crossref_metadata_2025_split huggingface dataset:
Unilateral Loss of Maxillary Molars in Young Mice Leads to Bilateral Condylar Adaptation and Degenerative Disease
Authors: Chen Christopher Phillip , Zhang Jiehua , Zhang Bin , Hassan Mohamed G. , Hane Kyle , Chen Caroline C. , Navarro Palacios Ana Alejandra , Kapila Sunil , Jheon Andrew H. , Goodwin Alice F. 
Published: May 2022

ABSTRACTThe adaptive response of the mandible and temporomandibular joint (TMJ) to altered occlusion in juvenile patients is presently unclear. To address this question, we established a mouse model in which all molars were extracted from the maxillary right quadrant in prepubertal, 3‐week‐old mice and analyzed morphological, tissue, cellular, and molecular changes in the mandible and condyle 3 weeks later. Unilateral loss of maxillary molars led to significant, robust, bilateral changes, primarily in condylar morphology, including anteroposterior narrowing of the condylar head and neck and increased convexity at the condylar surface, as determined by geometric morphometric analysis. Furthermore, both condyles in experimental mice exhibited a degenerative phenotype, which included decreased bone volume and increased mineral density near the condylar head surface compared to control mice. Changes in condylar morphology and mineralized tissue composition were associated with alterations in the cellular architecture of the mandibular condylar cartilage, including increased expression of markers for mature (Col2a1) and hypertrophic (Col10a1) chondrocytes, suggesting a shift toward differentiating chondrocytes. Our results show significant bilateral condylar morphological changes, alterations in tissue composition, cellular organization, and molecular expression, as well as degenerative disease, in response to the unilateral loss of teeth. Our study provides a relatively simple, tractable mouse tooth extraction system that will be of utility in uncovering the cellular and molecular mechanisms of condylar and mandibular adaptation in response to altered occlusion. © 2022 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.
In silico analyses of acetylcholinesterase (AChE) and its genetic variants in interaction with the anti‐Alzheimer drug Rivastigmine
Authors: Pereira Gabriel Rodrigues Coutinho , Gonçalves Lucas Machado , Abrahim‐Vieira Bárbara de Azevedo , De Mesquita Joelma Freire 
Published: May 2022

AbstractAlzheimer's disease (AD) is the leading cause of dementia worldwide. Despite causing great social and economic impact, there is currently no cure for AD. The most effective therapy to manage AD symptoms is based on acetylcholinesterase inhibitors (AChEi), from which rivastigmine presented numerous benefits. However, mutations in AChE, which affect approximately 5% of the population, can modify protein structure and function, changing the individual response to Alzheimer's treatment. In this study, we performed computer simulations of AChE wild type and variants R34Q, P135A, V333E, and H353N, identified by one or more genome‐wide association studies, to evaluate their effects on protein structure and interaction with rivastigmine. The functional effects of AChE variants were predicted using eight machine learning algorithms, while the evolutionary conservation of AChE residues was analyzed using the ConSurf server. Autodock4.2.6 was used to predict the binding modes for the hAChE–rivastigmine complex, which is still unknown. Molecular dynamics (MD) simulations were performed in triplicates for the AChE wild type and mutants using the GROMACS packages. Among the analyzed variants, P135A was classified as deleterious by all the functional prediction algorithms, in addition to occurring at highly conserved positions, which may have harmful consequences on protein function. The molecular docking results suggested that rivastigmine interacts with hAChE at the upper active‐site gorge, which was further confirmed by MD simulations. Our MD findings also suggested that the complex hAChE‐rivastigmine remains stable over time. The essential dynamics revealed flexibility alterations at the active‐site gorge upon mutations P135A, V333E, and H353N, which may lead to strong and nonintuitive consequences to hAChE binding. Nonetheless, similar binding affinities were registered in the MMPBSA analysis for the hAChE wild type and variants when complexed to rivastigmine. Finally, our findings indicated that the rivastigmine binding to hAChE is an energetically favorable process mainly driven by negatively charged amino acids.
Reduced insulin signaling and high glucagon in early insulin resistance impaired fast‐fed regulation of renal gluconeogenesis via insulin receptor substrate
Authors: Sharma Rajni , Sahoo Biswajit , Srivastava Aneesh , Tiwari Swasti 
Published: May 2022

AbstractGluconeogenesis is one of the key processes through which the kidney contributes to glucose homeostasis. Urinary exosomes (uE) have been used to study renal gene regulation noninvasively in humans and rodents. Recently, we demonstrated fast‐fed regulation of phosphoenolpyruvate carboxykinase (PEPCK), the rate‐limiting enzyme for gluconeogenesis, in human uE. The regulation was impaired in subjects with early insulin resistance. Here, we studied primary human proximal tubule cells (hPT) and human uE to elucidate a potential link between insulin resistance and fast‐fed regulation of renal PEPCK. We demonstrate that fasted hPTs had higher PEPCK and insulin receptor substrate‐2 (IRS2) mRNA and protein levels, relative to fed cells. The fast‐fed regulation was, however, attenuated in insulin receptor knockdown (IRKO) hPTs. The IRKO was confirmed by the blunted insulin‐induced response on PEPCK, PGC1α, p‐IR, and p‐AKT expression in IRKO cells. Exosomes secreted by the wild‐type or IRKO hPT showed similar regulation to the respective hPT. Similarly, in human uE, the relative abundance of IRS‐2 mRNA (to IRS1) was higher in the fasted state relative to the fed condition. However, the fast‐fed difference was absent in subjects with early insulin resistance. These subjects had higher circulating glucagon levels relative to subjects with optimal insulin sensitivity. Furthermore, in hPT cells, glucagon significantly induced PEPCK and IRS2 gene, and gluconeogenesis. IR knockdown in hPT cells further increased the gene expression levels. Together the data suggest that reduced insulin sensitivity and high glucagon in early insulin resistance may impair renal gluconeogenesis via IRS2 regulation.
Duality of bone morphogenetic proteins in cancer: A comprehensive analysis
Authors: Sharma Tanu , Kapoor Anmol , Mandal Chandi C. 
Published: May 2022

AbstractOver 20 different growth factors belonging to the bone morphogenetic proteins (BMPs) family have been identified, that were initially discovered as growth factors that promote osteogenesis, and play a vital role in bone remodeling and various developmental processes. Numerous studies have explored the aberrance level of BMPs in various cancer types, questioning their role in tumorigenesis. These growth factors have been studied extensively over the decades to define their function during cancer progression and metastasis. Nonetheless, the BMP expression profiles in clinical samples correlate with cancer prognosis. Based on clinical data, various in vitro, and in vivo findings, it has been reported that BMPs have dual roles, that is, they can act as a tumor suppressor, tumor promoter, and both. On contrary, some studies have reported that BMPs have an oncogenic role while others reported their tumor‐suppressive role. So, this creates a knowledge gap in the behavior of different types of BMPs. Thus, this review updates and bridges the knowledge gap while considering the dual behavior of various BMPs including BMP‐2, 4, 6, 7, 9, and 10. Moreover, the comprehensive analysis provides insight into the role of different BMPs in cancer potential and how the behavior of BMPs alters in the tissue‐dependent context in various cancers by modulating canonical SMAD signaling, various noncanonical pathways such as PI3K/AKT, NF‐κB, MAPK, STAT, cMYC, cJUN, and so forth. This review also enlightens the role of BMP heterodimers, several ligand‐binding proteins (agonists and antagonists), mutational status of BMP receptors, and the tumor microenvironment in relating to the bi‐functional aspects of the BMPs in various cancerous tissues by regulating the levels of BMP's canonical and noncanonical signals.
Bisphosphonate Use Is Not Associated With Tuberculosis Risk Among Patients With Osteoporosis: A Nationwide Cohort Study
Authors: Chen Jin‐Hua , Lee Chih‐Hsin , Lee Meng‐Rui , Huang Pei‐Yu , Yen Tzu‐Hsin , Lee Ming‐Chia , Tsai Ching‐Wen , Wang Jann‐Yuan , Lee Jen‐Ai 
Published: May 2022

AbstractBisphosphonates are considered an effective inhibitor of glutamine synthetase and thus can be used for treating tuberculosis (TB). However, its clinical benefit in TB remains unknown. We conducted a population‐based cohort study by using the Taiwan National Health Insurance Research Database and TB databases of the Taiwan Centers for Disease Control. Patients with osteoporosis and a history of bone fracture from 2007 to 2014 were identified. Among them, bisphosphonate users and propensity score–matched nonusers were selected. A stratified multivariable Cox proportional hazard regression model was employed to investigate the independent predictors of TB. Among 218 908 patients with osteoporosis and bone fracture, 46 842 bisphosphonate users and 46 842 propensity score–matched nonusers were selected. Within the 2‐year follow‐up, 723 patients—348 in the user group and 375 in the nonuser group—developed TB. Bisphosphonate use was not an independent predictor of TB in the multivariable Cox proportional hazard model (adjusted hazard ratio, 0.86; 95%CI, 0.71‐1.04); however, male sex, older age, being bedridden, and steroid use were independent risk factors. The real‐world data revealed that bisphosphonate use did not protect patients with osteoporosis against TB.
Siderophores of Bacillus pumilus promote 2‐keto‐L‐gulonic acid production in a vitamin C microbial fermentation system
Authors: Zhang Qian , Lin Ying , Shen Guozheng , Zhang Haihong , Lyu Shuxia 
Published: May 2022

AbstractThe precursor of vitamin C, 2‐keto‐l‐gulonic acid (2‐KLG), is bio‐converted from l‐sorbose by a microbial consortium of Ketogulonicigenium vulgare and a helper strain (Bacillus spp.). Most helper strains produce siderophores. To understand the effects of siderophores on promoting 2‐KLG yield, the siderophores of Bacillus pumilus SY‐A9 were purified and added to a monoculture fermentation system of K. vulgare 25B‐1. The results revealed that the titer of 2‐KLG reached 7.18 g/L within 60 h and increased by 71.45% when the added concentration of siderophores was 500 µg/L. Moreover, the increased production of 2‐KLG was accompanied by the overexpressed iron uptake system‐related genes, electron transfer chain‐related genes, ATP synthesis enzyme‐related genes, antioxidant enzyme‐related genes, and 2‐KLG producing enzyme‐related genes, which reduced oxidative stress and ensured the normal energy metabolism of K. vulgare 25B‐1. This study demonstrated that siderophores of the helper strain play a key role in the enhancement of 2‐KLG biosynthesis.
Black children matter too: Disrupting systemic oppression in education
Authors: Conner Charmaine 
Published: May 2022

AbstractThe purpose of this article is to propose child‐centered interventions that may support disrupting systemic oppression within the education system for Black children. The author shares Black children's experiences in the U.S. education system and how child‐centered interventions may be helpful for both school and school based clinical counselors.
The client–counselor encounter: Assessing relational depth and motivation to change in substance use disorder treatment
Authors: Woehler Elliott , Ray Dee 
Published: May 2022

AbstractThis nonexperimental field study examined the relationship between participant reported experiences of relational depth (RD) with their individual counselors in substance use disorder (SUD) treatment and participant reported motivation to change substance use. Participants in the study were clients enrolled in inpatient and outpatient levels of substance use disorder treatment.
Fusobacterium nucleatum mediates endothelial damage and increased permeability following single species and polymicrobial infection
Authors: Farrugia Cher , Stafford Graham P. , Gains Ashley F. , Cutts Antonia R. , Murdoch Craig 
Published: May 2022

AbstractBackgroundNumerous lines of evidence link periodontal pathobionts and their virulence factors with endothelial damage. Most research has been conducted using single species infections at the exclusion of other periodontal microorganisms that have been identified in vascular tissue. Here, we assessed endothelial infection with either single or mixed periodontal species infection and examined their effect on endothelial damage and permeability.MethodsCell surface abundance of platelet endothelial cell adhesion molecule‐1 (PECAM‐1) or endothelial permeability following infection with Porphyromonas gingivalis, Fusobacterium nucleatum subspecies (ssp) nucleatum, ssp polymorphum or Tannerella forsythia as single or mixed species infection was determined by flow cytometry and a fluorescent dextran permeability assay. Zebrafish embryos were infected systemically with either single or mixed species with mortality and disease measured over time.ResultsF. nucleatum ssp nucleatum, ssp polymorphum and P. gingivalis significantly reduced PECAM‐1 abundance in single species infection, whereas T. forsythia had no effect. F. nucleatum ssp polymorphum caused considerable mortality and morbidity in a zebrafish systemic infection model. Polymicrobial infection underscored the virulence of F. nucleatum ssp polymorphum in particular with increased endothelial cell death and reduced PECAM‐1 abundance in co‐infection studies with this organism. When injected systemically into zebrafish in polymicrobial infection, fluorescently labeled bacteria were distributed throughout the vasculature and cardiac region where, in some instances, they co‐localized with each other.ConclusionsThese data provide further evidence on the effects of F. nucleatum on endothelium adhesion molecule abundance and permeability while also highlighting the importance of performing polymicrobial infection to study the molecular mechanisms associated with periodontal pathogen‐induced vascular damage.
A Monte Carlo study of the relative biological effectiveness in surface brachytherapy
Authors: Valdes‐Cortez Christian , Niatsetski Yury , Perez‐Calatayud Jose , Ballester Facundo , Vijande Javier 
Published: May 2022

AbstractPurposeThis work aims to simulate clustered DNA damage from ionizing radiation and estimate the relative biological effectiveness (RBE) for radionuclide (rBT)‐ and electronic (eBT)‐based surface brachytherapy through a hybrid Monte Carlo (MC) approach, using realistic models of the sources and applicators.MethodsDamage from ionizing radiation has been studied using the Monte Carlo Damage Simulation algorithm using as input the primary electron fluence simulated using a state‐of‐the‐art MC code, PENELOPE‐2018. Two 192Ir rBT applicators, Valencia and Leipzig, one 60Co source with a Freiburg Flap applicator (reference source), and two eBT systems, Esteya and INTRABEAM, have been included in this study implementing full realizations of their geometries as disclosed by the manufacturer. The role played by filtration and tube kilovoltage has also been addressed.ResultsFor rBT, an RBE value of about 1.01 has been found for the applicators and phantoms considered. In the case of eBT, RBE values for the Esteya system show an almost constant RBE value of about 1.06 for all depths and materials. For INTRABEAM, variations in the range of 1.12–1.06 are reported depending on phantom composition and depth. Modifications in the Esteya system, filtration, and tube kilovoltage give rise to variations in the same range.ConclusionsCurrent clinical practice does not incorporate biological effects in surface brachytherapy. Therefore, the same absorbed dose is administered to the patients independently on the particularities of the rBT or eBT system considered. The almost constant RBE values reported for rBT support that assumption regardless of the details of the patient geometry, the presence of a flattening filter in the applicator design, or even significant modifications in the photon energy spectra above 300 keV. That is not the case for eBT, where a clear dependence on the eBT system and the characteristics of the patient geometry are reported. A complete study specific for each eBT system, including detailed applicator characteristics (size, shape, filtering, among others) and common anatomical locations, should be performed before adopting an existing RBE value.
The mediating effects of social support on the influencing relationship between grit and academic burnout of the nursing students
Authors: Kim Hae‐Ok , Lee Insook 
Published: May 2022

AbstractAim(s)This study aimed to examine the social supports' mediating effects on the relationship between grit and academic burnout in nursing students.DesignThis was a descriptive study.MethodsThis study was conducted in two nursing departments in Korea, utilizing a convenience sample of 158 nursing students. Data were analysed using hierarchical multiple regression analysis and bootstrapping to verify the mediation effect.ResultsThe grit's direct effect on academic burnout and indirect effect with social support on academic burnout were statistically significant. Social support mediated the relationship between grit and academic burnout. Social support can improve grit and reduce academic burnout. Social support programs for nursing students should be implemented to prevent/reduce academic burnout.
Web‐based chlamydia education for university students: A pilot project
Authors: Russell Nancy G. , Sharps Phyllis W. , Sloand Elizabeth 
Published: May 2022

AbstractAimsChlamydia disproportionately affects individuals aged 15–24 years. A lack of chlamydia knowledge in this high‐risk group likely contributes to decreased testing, but interventions to increase chlamydia knowledge in this population are not well‐described in the literature. The purpose of this pilot project was to increase chlamydia knowledge in a sample of university students using nurse‐developed web‐based education.DesignA pre‐ and post‐test design was used to evaluate participant knowledge of chlamydia before and after completing a nurse‐developed web‐based education intervention designed for university students.MethodsForty‐seven undergraduate students at one U.S. university participated. A focus group and scientific evidence informed the development of the web‐based education.ResultsParticipants had a significant increase in chlamydia knowledge after completing the online educational intervention (M = 8.0, SD = 0.000) compared to baseline (M = 6.5, SD = 1.5), t(33) = −5.821, p < .0001. Pilot results provide promising evidence that web‐based nurse‐developed education designed specifically for university students can increase chlamydia knowledge.
Factors associated with pregnancy uptake decisions among seropositive HIV people receiving antiretroviral therapy in sub‐Saharan Africa: A systematic review
Authors: Doat Abdul Razak , Amoah Roberta Mensima , Konlan Kennedy Diema , Konlan Kennedy Dodam , Abdulai Juliana Asibi , Kukeba Margaret W. , Mohammed Iddrisu , Saah Joel Afram 
Published: May 2022

AbstractAimThis study determined the factors associated with pregnancy uptake decision among seropositive HIV people receiving antiretroviral therapy in sub‐Saharan Africa.DesignSystematic review.MethodsThe population, intervention, comparison and outcomes framework was adopted to search for literature after a scoping review using the preferred reporting items for systematic reviews and meta‐analyses guidelines adopted in searching, and screening articles from four databases (PubMed, Cumulative Index to Nursing and Allied Health Literature, Embase, and Google scholar) to find 12 articles suitable for this study.ResultsMotivators of pregnancy uptake among HIV‐positive women include desire to have children, knowledge about PMTCT, cultural duty for married women to have children, and household income. Demotivating factors included the modern method of contraception and burden associated with pregnancy.ConclusionThere is a need to improve on services that reduce conception‐related risks especially for women who choose to conceive and to incorporate fertility‐related counselling into HIV treatment services.
Plasma activated liquid synergistically enhances response to radiation for improved cancer therapy
Authors: Harley Juliette C. , Suchowerska Natalka , Rogers Linda J. , Lo Helen , Choong Ee Siang , McKenzie David R. 
Published: May 2022

AbstractPlasma activated liquid (PAL) is an emerging cancer treatment. Two prostate cell lines and one melanoma cell line were used in clonogenic assays to assess the cytotoxicity of PAL and radiation individually and in combination, using the multiplicative survival method to quantify interactions between the treatments. PAL applied before a dose of radiation synergistically increases cytotoxicity in cancer cells, while in immortalized normal cells, the combined treatment was found to be antagonistic. These results demonstrate the potential to improve the therapeutic window of cancer treatment, giving a higher cancer response rate with less toxicity.
Involvement of β‐adrenoceptors in the cardiovascular responses induced by selective adenosine A2A and A2B receptor agonists
Authors: Wragg Edward S. , Pannucci Patrizia , Hill Stephen J. , Woolard Jeanette , Cooper Samantha L. 
Published: May 2022

AbstractA2A and A2B adenosine receptors produce regionally selective regulation of vascular tone and elicit differing effects on mean arterial pressure (MAP), whilst inducing tachycardia. The tachycardia induced by the stimulation of A2A or A2B receptors has been suggested to be mediated by a reflex increase in sympathetic activity. Here, we have investigated the role of β1‐ and β2‐adrenoceptors in mediating the different cardiovascular responses to selective A2A and A2B receptor stimulation. Hemodynamic variables were measured in conscious male Sprague‐Dawley rats (350–450 g) via pulsed Doppler flowmetry. The effect of intravenous infusion (3 min per dose) of the A2A‐selective agonist CGS 21680 (0.1, 0.3, 1.0 µg.kg−1.min−1) or the A2B‐selective agonist BAY 60–6583 (4.0, 13.3, 40.0 µg.kg−1.min−1) in the absence or following pre‐treatment with the non‐selective β‐antagonist propranolol (1.0 mg.kg−1), the selective β1‐antagonist CGP 20712A (200 µg.kg−1), or the selective β2‐antagonist ICI 118,551 (2.0 mg.kg−1) was investigated (maintenance doses also administered). CGP 20712A and propranolol significantly reduced the tachycardic response to CGS 21680, with no change in the effect on MAP. ICI 118,551 increased BAY 60–6583‐mediated renal and mesenteric flows, but did not affect the heart rate response. CGP 20712A attenuated the BAY 60–6583‐induced tachycardia. These data imply a direct stimulation of the sympathetic activity via cardiac β1‐adrenoceptors as a mechanism for the A2A‐ and A2B‐induced tachycardia. However, the regionally selective effects of A2B agonists on vascular conductance were independent of sympathetic activity and may be exploitable for the treatment of acute kidney injury and mesenteric ischemia.