bluuebunny/crossref_metadata_2025_split huggingface dataset:
Osteoporosis and periodontal diseases – An update on their association and mechanistic links
Authors: Yu Bo , Wang Cun‐Yu 
Published: March 2022

AbstractPeriodontitis and osteoporosis are prevalent inflammation‐associated skeletal disorders that pose significant public health challenges to our aging population. Both periodontitis and osteoporosis are bone disorders closely associated with inflammation and aging. There has been consistent intrigue on whether a systemic skeletal disease such as osteoporosis will amplify the alveolar bone loss in periodontitis. A survey of the literature published in the past 25 years indicates that systemic low bone mineral density (BMD) is associated with alveolar bone loss, while recent evidence also suggests a correlation between clinical attachment loss and other parameters of periodontitis. Inflammation and its influence on bone remodeling play critical roles in the pathogenesis of both osteoporosis and periodontitis and could serve as the central mechanistic link between these disorders. Enhanced cytokine production and elevated inflammatory response exacerbate osteoclastic bone resorption while inhibiting osteoblastic bone formation, resulting in a net bone loss. With aging, accumulation of oxidative stress and cellular senescence drive the progression of osteoporosis and exacerbation of periodontitis. Vitamin D deficiency and smoking are shared risk factors and may mediate the connection between osteoporosis and periodontitis, through increasing oxidative stress and impairing host response to inflammation. With the connection between systemic and localized bone loss in mind, routine dental exams and intraoral radiographs may serve as a low‐cost screening tool for low systemic BMD and increased fracture risk. Conversely, patients with fracture risk beyond the intervention threshold are at greater risk for developing severe periodontitis and undergo tooth loss. Various Food and Drug Administration‐approved therapies for osteoporosis have shown promising results for treating periodontitis. Understanding the molecular mechanisms underlying their connection sheds light on potential therapeutic strategies that may facilitate co‐management of systemic and localized bone loss.
Fusobacterium nucleatum and cancer
Authors: Alon‐Maimon Tamar , Mandelboim Ofer , Bachrach Gilad 
Published: March 2022

AbstractAccumulating evidence demonstrates that the oral pathobiont Fusobacterium nucleatum is involved in the progression of an increasing number of tumors types. Thus far, the mechanisms underlying tumor exacerbation by F. nucleatum include the enhancement of proliferation, establishment of a tumor‐promoting immune environment, induction of chemoresistance, and the activation of immune checkpoints. This review focuses on the mechanisms that mediate tumor‐specific colonization by fusobacteria. Elucidating the mechanisms mediating fusobacterial tumor tropism and promotion might provide new insights for the development of novel approaches for tumor detection and treatment.
Interconnection of periodontal disease and comorbidities: Evidence, mechanisms, and implications
Authors: Hajishengallis George 
Published: March 2022

AbstractPeriodontitis, a microbiome‐driven inflammatory disease of the tooth‐attachment apparatus, is epidemiologically linked with other disorders, including cardio‐metabolic, cognitive neurodegenerative and autoimmune diseases, respiratory infections, and certain cancers. These associations may, in part, be causal, as suggested by interventional studies showing that local treatment of periodontitis reduces systemic inflammation and surrogate markers of comorbid diseases. The potential cause‐and‐effect connection between periodontitis and comorbidities is corroborated by studies in preclinical models of disease, which additionally provided mechanistic insights into these associations. This overview discusses recent advances in our understanding of the periodontitis‐systemic disease connection, which may potentially lead to innovative therapeutic options to reduce the risk of periodontitis‐linked comorbidities.
Oral bacteria, oral health, and adverse pregnancy outcomes
Authors: Xu Biyang , Han Yiping W. 
Published: March 2022

AbstractThe link between oral health and adverse pregnancy outcomes has been suggested by numerous epidemiological studies. More recent studies indicate the relationship between severity of periodontal disease and adverse pregnancy outcomes. Two virulence mechanisms are proposed: direct invasion of oral microorganisms or their components into the fetal‐placenta unit and inflammatory mediators produced in the oral cavity affecting the fetal‐placenta unit. While interventional periodontal therapy still yielded contradictory results, animal studies suggest that maternal supplementation of omega‐3 fatty acids protects the fetus by suppressing inflammation as well as bacteria proliferation in the placenta. This article reviews the recent epidemiological, mechanistic, interventional, and therapeutic studies of oral health and adverse pregnancy outcomes.
Nurses' sources of information to inform clinical practice: An integrative review to guide evidence‐based practice
Authors: Fossum Mariann , Opsal Anne , Ehrenberg Anna 
Published: March 2022

AbstractBackgroundEvidence‐based practice in nursing is challenging and relies on the sources of information used by nurses to inform clinical practice. An integrative review from 2008 revealed that nurses more frequently relied on information from colleagues than information from high‐level sources such as systematic reviews and evidence‐based clinical practice guidelines.AimsTo describe the information sources used by registered nurses to inform their clinical practice.MethodsAn integrative review was conducted according to the PRISMA guidelines, based on empirical research studies published from January 2007 until June 2021. The included studies were appraised, following which the identified sources of information from quantitative studies were compiled and ranked. Finally, the qualitative text data were summarized into categories.ResultsFifty‐two studies from various countries were included. The majority of studies employed a quantitative design and used original instruments. Peers were ranked as the number one source of information to inform nurses' clinical practice. However, computers and reference materials are now ranked among the top four most used information sources.Linking Evidence to ActionImprovement in computer and information searching skills, as well as the availability of computerized decision support tools, may contribute to nurses' frequent use of digital sources and reference material to inform clinical practice. This review shows that nurses' most frequently reported peer nurses as their source of information in clinical practice. Information sources such as computers and reference materials were ranked higher, and information from patients was ranked lower than in the 2008 review. Developing and standardizing instruments and ensuring high‐quality study design is critical for further research on nurses’ sources of information for clinical practice.
The HVCN1 voltage‐gated proton channel contributes to pH regulation in canine ventricular myocytes
Authors: Ma Jianyong , Gao Xiaoqian , Li Yutian , DeCoursey Thomas E. , Shull Gary E. , Wang Hong‐Sheng 
Published: March 2022

AbstractRegulation of intracellular pH (pHi) in cardiomyocytes is crucial for cardiac function; however, currently known mechanisms for direct or indirect extrusion of acid from cardiomyocytes seem insufficient for energetically efficient extrusion of the massive H+ loads generated under in vivo conditions. In cardiomyocytes, voltage‐sensitive H+ channel activity mediated by the HVCN1 proton channel would be a highly efficient means of disposing of H+, while avoiding Na+ loading, as occurs during direct acid extrusion via Na+/H+ exchange or indirect acid extrusion via Na+–HCO3− cotransport. PCR and immunoblotting demonstrated expression of HVCN1 mRNA and protein in canine heart. Patch clamp analysis of canine ventricular myocytes revealed a voltage‐gated H+ current that was highly H+‐selective. The current was blocked by external Zn2+ and the HVCN1 blocker 5‐chloro‐2‐guanidinobenzimidazole. Both the gating and Zn2+ blockade of the current were strongly influenced by the pH gradient across the membrane. All characteristics of the observed current were consistent with the known hallmarks of HVCN1‐mediated H+ current. Inhibition of HVCN1 and the NHE1 Na+/H+ exchanger, singly and in combination, showed that either mechanism is largely sufficient to maintain pHi in beating cardiomyocytes, but that inhibition of both activities causes rapid acidification. These results show that HVCN1 is expressed in canine ventricular myocytes and provides a major H+ extrusion activity, with a capacity similar to that of NHE1. In the beating heart in vivo, this activity would allow Na+‐independent extrusion of H+ during each action potential and, when functionally coupled with anion transport mechanisms, could facilitate transport‐mediated CO2 disposal.Key points
Intracellular pH (pHi) regulation is crucial for cardiac function, as acidification depresses contractility and causes arrhythmias. H+ ions are generated in cardiomyocytes from metabolic processes and particularly from CO2 hydration, which has been shown to facilitate CO2 venting from mitochondria.
Currently, the NHE1 Na+/H+ exchanger is viewed as the dominant H+ extrusion mechanism in cardiac muscle.
We show that the HVCN1 voltage‐gated proton channel is present and functional in canine ventricular myocytes, and that HVCN1 and NHE1 both contribute to pHi regulation.
HVCN1 provides an energetically efficient mechanism of H+ extrusion that would not cause Na+ loading, which can cause pathology, and that could contribute to transport‐mediated CO2 disposal.
These results provide a major advance in our understanding of pHi regulation in cardiac muscle.
How Leadership Should Be Exercised in Early Childhood Education?
Authors: Cabrera-Murcia Elsa Piedad 
Published: March 2022

This research article gathers the perceptions about how directors and pedagogical teams understand and experience leadership within five Junji preschools in Chile. Data were collected for from five semi-structured interviews and a participant observation. Findings suggest three forms of exercising leadership: pedagogical,supervisory, and administrative. In all cases, there are the same threats to leadership. The study uncovers some personal skills and characteristics common to the ways of leading. The article also highlights the context as a key element to the exercise of leadership, and the importance of modeling collaborative cultures, which consider the centrality of children's learning in preschool education.
¿Por qué directores y tesistas deciden discontinuar la relación pedagógica?
Authors: Fernandez-Fastuca Lorena 
Published: March 2022

La dirección de tesis es un pilar de la formación de posgrado. Por ello, se propone analizar la relación director-tesista indagando las razones que pueden llevar a su discontinuidad desde la perspectiva de ambos. Se realizó un estudio cuantitativo descriptivo, con base en una encuesta diseñada ad hoc, que se aplicó a una muestra no representativa de 1607 directores y tesistas de universidades argentinas. El 58 % de los directores ha discontinuado este vínculo. Algunas razones son: insuficiente dedicación del tesista e insuficiente seguimiento de las indicaciones. Para los tesistas el motivo central es la falta de dedicación del director.
How to Use the Levers of Modularity Properly—Linking Modularization to Economic Targets
Authors: Schwede Lea-Nadine , Greve Erik , Krause Dieter , Otto Kevin , Moon Seung Ki , Albers Albert , Kirchner Eckhard , Lachmayer Roland , Bursac Nikola , Inkermann David , Rapp Simon , Hausmann Maximilian , Schneider Jannik 
Published: March 2022

Abstract
Product developers are faced with the challenge of covering an ever-increasing external variety with as little internal variety as possible. Modular product architectures offer one way of resolving the challenge. They have an impact on all life phases and on economic targets. These effects are represented in the Impact Model of Modular Product Families. A large number of modularization methods can be found in the literature. The modularization methods consist of different activities: decomposition of product, analysis and revision of components, and reintegration to modules. Module drivers play a major role in reintegration, as they determine which components together form a module. It is not yet clear what effects different modularization methods involving different module drivers have on economic targets. For this reason, the module drivers are examined in their role as levers of modularity and integrated into the Impact Model via access points. By documenting the results in a specially developed uniform method step description and the Impact Model, we enable the selection of modularization methods with regard to their economic impact. The introduction is followed by the state of research. In Sec.3, the research problem and the research approach are presented. In Sec.4, the generic method step description is applied to seven modularization methods. Based thereon, the modularization methods are compared with each other with regard to their addressed economic objectives. In an explanatory example, the method selection made possible by this is presented. Finally, the results are discussed and an outlook is given.
Effect of the Addition of Copper Particles on the Thermoelectric Properties of the Ca3Co4O9 + δ Ceramics Produced by Two-Step Sintering
Authors: Klyndyuk A. I. , Chizhova E. A. , Latypov R. S. , Shevchenko S. V. , Kononovich V. M. 
Published: March 2022

Abstract
Composite thermoelectric materials based on layered calcium cobaltite Ca3Co4O9 + δ doped with copper particles were synthesized by two-step sintering, and their microstructure, and electrotransport and thermoelectric properties were studied. It was determined that the introduction of copper particles into the ceramics improves their sinterability at moderate sintering temperatures (Tsint ≤ 1273 K), leading to a decrease in the porosity of the samples and an increase in their electrical conductivity and power factor, whereas the oxidation of copper to less conductive copper(II) oxide significantly decreases the electrical conductivity and power factor of the ceramics sintered at elevated temperatures (Tsint ≥ 1373 K). The power factor is maximum for the Ca3Co4O9 + δ + 3 wt % Cu ceramic sintered at 1273 K (335 μW/(m K2) at a temperature of 1100 K), which is by a factor of 2.3 higher than the power factor of the base material Ca3Co4O9 + δ with the same thermal history (145 μW/(m K2) at 1100 K) and more than 3 times higher than the power factor of the Ca3Co4O9+δ ceramic synthesized by the conventional solid-phase method.
Longitudinal study of the effects of price and promotion incentives on purchases of unhealthy foods: evidence for restricting food promotions
Authors: Kopasker Daniel , Ejebu Ourega-Zoé , Norwood Patricia , Ludbrook Anne 
Published: March 2022

ObjectivesTaxes and restrictions on promotions have recently been proposed as policy instruments to reduce consumption of unhealthy foods. The objective of this study is to add to the limited evidence on the comparative effectiveness of price changes, price promotions and volume promotions in changing household purchasing of unhealthy foods, using biscuits, crisps and savoury snacks as examples.DesignLongitudinal regression analysis of consumer microdata.SettingSecondary data on itemised household purchases of biscuits, crisps and savoury snacks from 2006 to 2012.ParticipantsSample of 3024 households in Scotland.Main outcome measuresChanges in the number of calories (kcal) purchased in the product category by a household caused by changes in the price for the product category, any temporary in-store price promotions and any temporary in-store volume promotions. Changes are measured at the mean, median, 25th percentile and 75th percentile of the household purchasing distribution for the full sample. Subgroup analyses were conducted by household income band and for households with and without children.ResultsBetween product categories, the scale of purchasing response to incentives varies significantly. Within product categories, the mean calories (kcal) purchased by a household are more responsive to any volume promotion than to price or any price promotion for all product categories. As the volume of items purchased increases, households are less responsive to price, less responsive to any volume promotion and more responsive to any price promotion. Statistically significant differences are observed between household income groups in their response to price and promotion incentives within the biscuits category only. In cases where statistically significant differences are observed, households with children are more responsive to promotion and price incentives than households without children.ConclusionsFor all product categories analysed (biscuits, crisps and savoury snacks), household purchasing is most responsive to any volume promotion. Therefore, assuming the response of consumers to incentives remains constant following legislation, the most effective policy instrument to reduce the calorie intake from these products may be a ban on volume promotions.
Effectiveness and cost-effectiveness of a combined lifestyle intervention compared with usual care for patients with early-stage knee osteoarthritis who are overweight (LITE): protocol for a randomised controlled trial
Authors: Jansen Nuria E J , Schiphof Dieuwke , Oei Edwin , Bosmans Judith , van Teeffelen Jolande , Feleus Anita , Runhaar Jos , van Meurs Joyce , Bierma-Zeinstra Sita M A , van Middelkoop Marienke 
Published: March 2022

IntroductionObesity is the most important modifiable risk factor for knee osteoarthritis (KOA). Especially in an early stage of the disease, weight loss is important to prevent further clinical and structural progression. Since 2019, general practitioners (GPs) in the Netherlands can refer eligible patients to a combined lifestyle intervention (GLI) to promote physical activity, healthy nutrition and behavioural change. However, GPs scarcely refer patients with KOA to the GLI potentially due to a lack of evidence about the (cost-)effectiveness. The aim of this study is to determine the (cost-)effectiveness of the GLI for patients with early-stage KOA in primary care.Methods and analysisFor this pragmatic, multi-centre randomised controlled trial, 234 participants (aged 45–70 years) with National Institute for Health and Care Excellence (NICE) guideline diagnosis of clinical KOA and a body mass index above 25 kg/m2will be recruited using a range of online and offline strategies and from general practices in the Netherlands. Participants will receive nine 3-monthly questionnaires. In addition, participants will be invited for a physical examination, MRI assessment and blood collection at baseline and at 24-month follow-up. After the baseline assessment, participants are randomised to receive either the 24-month GLI programme in addition to usual care or usual care only. Primary outcomes are self-reported knee pain over 24 months, structural progression on MRI at 24 months, weight loss at 24 months, as well as societal costs and Quality-Adjusted Life-Years over 24-month follow-up. Analyses will be performed following the intention-to-treat principle using linear mixed-effects regression models.Ethics and disseminationEthical approval was obtained through the Medical Ethical Committee of the Erasmus MC University Medical Center Rotterdam, The Netherlands (MEC-2020-0943). All participants will provide written informed consent. The results will be disseminated through publications in peer-reviewed journals, presentations at international conferences and among study participants and healthcare professionals.Trial registration numberNetherlands Trial Registry (NL9355).
Selumetinib in combination with dexamethasone for the treatment of relapsed/refractory RAS-pathway mutated paediatric and adult acute lymphoblastic leukaemia (SeluDex): study protocol for an international, parallel-group, dose-finding with expansion phase I/II trial
Authors: Menne Tobias , Slade Daniel , Savage Joshua , Johnson Sarah , Irving Julie , Kearns Pamela , Plummer Ruth , Shenton Geoff , Veal Gareth J , Vormoor Britta , Vormoor Josef , Billingham Lucinda 
Published: March 2022

IntroductionEvent-free survival rates at 15 years for paediatric patients with relapsed/refractory acute lymphoblastic leukaemia (ALL) are 30%–50%, with 5-year survival for adult patients only 20%. Many patients with newly diagnosed and relapsed ALL harbour somatic RAS-signalling activation mutations. Induction therapy for ALL involves steroids, with preclinical data suggesting the combination of dexamethasone with the MEK1/2 inhibitor, selumetinib (ARRY-142886) has a synergistic anticancer effect.Methods and analysisThe SeluDex trial is an international, parallel-group, dose-finding with expansion, phase I/II trial to assess the selumetinib/dexamethasone combination in adult and paediatric patients with relapsed/refractory, RAS pathway mutant ALL. The Cancer Research UK Clinical Trials Unit at University of Birmingham is the UK Coordinating Centre, with national hubs in Copenhagen, Denmark; Monza, Italy; Münster, Germany; Paris, France; and Utrecht, Netherlands. Patients with morphologically proven relapsed/refractory or progressive B-cell precursor or T-cell ALL, with demonstrated RAS pathway activating mutations are eligible. Adult patients are>18 years old, ECOG<2 and paediatric <18 years old, Lansky play scale ≥60% or Karnofsky score ≥60%. Phase I primary objective is the recommended phase II dose of selumetinib as defined by occurrence/non-occurrence of dose limiting toxicities using the continual reassessment method; phase II will evaluate preliminary antileukaemic activity of the combination, as defined by morphological response 28 days post-treatment using a Bayesian approach. Target recruitment is between 26 and 42 patients (minimum 13 and maximum 21 per group), depending the number of phase I patients included in phase II.Ethics and disseminationMedical ethical committees of all the participating countries have approved the study protocol; initial (UK) ethics approval (17/YH/0123) was granted by Yorkshire & The Humber—Leeds West Research Ethics Committee. Participants are required to provide written informed consent/assent. Results will be disseminated through national and international presentations and peer-reviewed publications.Trial registration numberISRCTN92323261.