bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reciprocal role of PLAP‐1 in HIF‐1α‐mediated responses to hypoxia
Authors: Takedachi Masahide , Yamamoto Satomi , Kawasaki Kohsuke , Shimomura Junpei , Murata Mari , Morimoto Chiaki , Hirai Asae , Kawakami Kazuma , Bhongsatiern Phan , Iwayama Tomoaki , Sawada Keigo , Yamada Satoru , Murakami Shinya 
Published: February 2022

AbstractObjectiveTo investigate the mutual regulation of hypoxia‐inducible factor (HIF)‐1α activity and periodontal ligament‐associated protein‐1 (PLAP‐1) expression in human periodontal ligament cells (HPDLs).BackgroundCellular responses to hypoxia regulate various biological events (e.g., inflammation and tissue regeneration) through activation of HIF‐1α. PLAP‐1, an extracellular matrix protein preferentially expressed in the periodontal ligament, plays important roles in the functions of HPDLs. Although PLAP‐1 expression has been demonstrated in hypoxic regions, the involvement of PLAP‐1 in responses to hypoxia has not been revealed.MethodsHPDLs were cultured under normoxic (20% O2) or hypoxic (1% O2) conditions with or without deferoxamine mesylate (chemical hypoxia inducer) or chetomin (HIF signaling inhibitor). Expression levels of PLAP‐1 and HIF‐1α were examined by real‐time reverse transcription‐polymerase chain reaction and western blot analysis. Luciferase reporter assays of HIF‐1α activity were performed using 293T cells stably transfected with a hypoxia response element (HRE)‐containing luciferase vector in the presence or absence of recombinant PLAP‐1 or PLAP‐1 gene transfection.ResultsCultivation under hypoxic conditions elevated the gene and protein expression levels of PLAP‐1 in HPDLs. Deferoxamine mesylate treatment also enhanced PLAP‐1 expression in HPDLs. Hypoxia‐induced PLAP‐1 expression was significantly suppressed in the presence of chetomin. PLAP‐1‐suppressed HPDLs showed increased HIF‐1α accumulation in the nucleus during culture under hypoxic conditions, but not in the presence of recombinant PLAP‐1. In the presence of recombinant PLAP‐1, hypoxia‐induced HRE activity of 293T cells was significantly suppressed in a dose‐dependent manner. Transfection of the PLAP‐1 gene resulted in a significant reduction of HRE activity during culture under hypoxic conditions.ConclusionPLAP‐1 expression is upregulated under hypoxic conditions through HIF‐1α activation. Moreover, hypoxia‐induced PLAP‐1 expression regulates HIF‐1α signaling.
Representativeness in Six Waves of Cross-National Online Survey (CRONOS) Panel
Authors: Maslovskaya Olga , Lugtig Peter 
Published: February 2022

Abstract
Driven by innovations in the digital space, surveys have started to move towards online data collection across the world. However, evidence is needed to demonstrate that online data collection strategy will produce reliable data which could be confidently used to inform policy decisions. This issue is even more pertinent in cross-national surveys, where the comparability of data is of the utmost importance. Due to differences in internet coverage and willingness to participate in online surveys across Europe, there is a risk that any strategy to move existing surveys online will introduce differential coverage and nonresponse bias. This paper explores representativeness across waves in the first cross-national online probability-based panel (CRONOS) by employing R-indicators that summarize the representativeness of the data across a range of variables. The analysis allows comparison of the results over time and across three countries (Estonia, Great Britain and Slovenia). The results suggest that there are differences in representativeness over time in each country and across countries. Those with lower levels of education and those who are in the oldest age category contribute more to the lack of representativeness in the three countries. However, the representativeness of CRONOS panel does not become worse when compared to the regular face-to-face interviewing conducted in the European Social Survey (ESS).
Plate corner subduction and rapid localized exhumation: Insights from3Dcoupled geodynamic and geomorphological modelling
Authors: Koptev Alexander , Nettesheim Matthias , Ehlers Todd A. 
Published: February 2022

AbstractRapid, localized exhumation has been reported at many plate corners between adjacent subduction/collision segments. Here we use a fully‐coupled geodynamic and geomorphological modelling approach to investigate overriding plate deformation and resulting rock uplift patterns in these narrow, cuspate regions. In this study, we focus on the effects of internal deformation within a subducting convex‐upward‐shaped indenter and the strength of the interface between the upper and downgoing plate. The strongest localization of high rock uplift rates in the region above the indenter apex is predicted in experiments with a deformable lower plate, a weak interface layer and lateral shortening accommodated only by subduction (i.e., without an upper plate advance component). Our results suggest that bull’s eye shaped structures characterized by young thermochronological ages can, in principle, be reproduced numerically when taking into account a non‐rigid subducting plate together with complex brittle‐ductile rheology and stratification of the overriding lithosphere and realistically implemented fluvial erosion at its surface.
Detrital zircon record of the Mesoproterozoic Belt basin and implications for horizontal and vertical tectonic models
Authors: Parker Stuart D. , Hendrix Marc S. 
Published: February 2022

ABSTRACT
It is debated whether plate tectonics (horizontal tectonics) or single-lid tectonics (vertical tectonics) dominated the Mesoproterozoic Era. Either rifting of the Nuna/Columbia supercontinent or a localized vertical subsidence and tectonism mechanism within a single tectonic plate is likely recorded in Mesoproterozoic basins. This study summarizes detrital zircon samples from the Mesoproterozoic Belt and Purcell Supergroups and Lemhi subbasin of the western United States and Canada and tests competing rift and intracratonic basin models. Rift models take the observed detrital zircon trends to mean that a non-Laurentian (ca. 1.6–1.5 Ga) detrital zircon component becomes completely absent higher in the section, signifying rifting of the Nuna/Columbia supercontinent at ca. 1.4 Ga. Intracratonic models acknowledge this observed shift in provenance but interpret a long-lived intracratonic setting for the basin following an earlier failed rifting event. The fundamental question is whether the Belt basin represents a failed or successful rift. We used statistical comparison of 72 detrital zircon signatures, reported in the literature and presented in this study, to test the rift model. Samples are not evenly distributed across the basin or its stratigraphy. Non-Laurentian grains are spatially restricted to the northwest part of the basin but are present in all groups, suggesting that the apparent loss of the non-Laurentian population is an artifact of sampling bias. Like stratigraphic boundaries and facies changes, mixing trends are gradual, not sharp or sudden, signifying progressive reworking of Proterozoic zircons and transport from all sides. Archean zircons are localized near the edges of Archean blocks, signifying local down-dropping along cratonic margins. The rift model is therefore rejected in favor of the intracratonic model for the Belt basin on the basis of variable mixing between non-Laurentian and Laurentian sources in both pre–Missoula Group and Missoula Group strata. Far away from plate margins, sediment incrementally filled topographic depressions created by densified and thinned Proterozoic crustal blocks, resulting in vertical down-dropping along preexisting sutures with neighboring Archean blocks. More systematic detrital zircon studies are needed in order to accurately quantify provenance trends in space and time. Continued investigation of the Belt basin may reveal underappreciated or unrecognized vertical tectonic processes that may explain Mesoproterozoic rocks more accurately.
Multimorbidity and catastrophic health expenditure among patients with diabetes in China: a nationwide population-based study
Authors: Fu Yu , Chen Mingsheng , Si Lei 
Published: February 2022

IntroductionMultimorbidity is common among patients with diabetes and can lead to catastrophic health expenditure (CHE) for their families. This study aims to investigate the prevalence of multimorbidity and CHE among people with diabetes in China, and the association between multimorbidity and CHE and whether this is influenced by socioeconomic status and health insurance type.MethodsA national survey was conducted in China in 2013 that included 8471 people aged ≥18 years who were living with diabetes. The concentration curve and concentration index were used to measure socioeconomic-related inequalities. Factors influencing CHE and the impact of multimorbidity on CHE according to socioeconomic status and health insurance type were examined by logistic regression.ResultsThere were 5524 (65.2%) diabetes patients with multimorbidity. The prevalence of CHE was 56.6%, with a concentration index of −0.030 (95% CI −0.035 to –0.026). For each additional chronic disease, the probability of CHE increased by 39% (OR=1.39, 95% CI 1.31 to 1.47). Factors that were positively associated (p<0.05) with CHE included older age; male sex; lower educational level; being retired, unemployed or jobless; being a non-smoker and non-drinker; having had no physical examination; lower socioeconomic status; being in an impoverished family; and residing in the central or western regions. Among participants with Urban Employee Basic Medical Insurance, Urban Resident Basic Medical Insurance, and New Rural Cooperative Medical Scheme, the probability of CHE increased by 32% (OR=1.32, 95% CI 1.23 to 1.43), 43% (OR=1.43, 95% CI 1.24 to 1.65) and 47% (OR=1.47, 95% CI 1.33 to 1.63), respectively, with each additional chronic disease. The association between multimorbidity and CHE was observed across all health insurance types irrespective of socioeconomic status.ConclusionsMultimorbidity affects about two-thirds of Chinese patients with diabetes. Current health insurance schemes offer limited protection against CHE to patients’ families.
Person-centred care provided by a multidisciplinary primary care team to improve therapeutic adequacy in polymedicated elderly patients (PCMR): randomised controlled trial protocol
Authors: Rovira Carol , Modamio Pilar , Pascual Joaquim , Armengol Joan , Ayala Cristian , Gallego Joan , Mariño Eduardo L , Ramirez Anna 
Published: February 2022

IntroductionThe increase in elderly population has led to an associated increase in multiple pathologies, frailty, polypharmacy, healthcare costs, decreased quality of life and mortality. We designed an intervention based on person-centred care model. This article outlines a study protocol, which aims to explore the effects of the intervention to improve therapeutic adequacy in polymedicated elderly patients.Methods and analysisAn open, randomised, multicentre, controlled clinical trial. The study population includes polymedicated (≥8 prescription medications) patients ≥75 years old. In the intervention group, the multidisciplinary team (primary care pharmacist, family doctor and nurse) will meet to carry out multidimensional reviews (frailty, clinical complexity, morbidity and therapeutic adequacy) of the study subjects. If changes are proposed to the treatment plan, a clinical interview will be conducted with the patient to agree on changes in accordance with their preferences. Follow-up visits will be scheduled at 6 and 12 months. In the control group, where the usual clinical practice will be followed, the necessary data will be collected to compare the results.The key variables are the variation in the mean number of incidents (potentially inappropriate prescription) per patient, the number of medications, the number of changes implemented to the treatment plan and the variation in the number of hospital admissions.Ethics and disseminationThis study was approved by the Ethics Committee of the IDIAPJGol and by the University of Barcelona’s Bioethics Commission. The results are expected to be published in peer reviewed open-access journals, and as part of a doctoral thesis.Trial registration numberNCT04188470. Pre-results.
Food insecurity status is of added value in explaining poor health: a cross-sectional study among parents living in disadvantaged neighbourhoods in the Netherlands
Authors: van der Velde Laura A , Steyerberg Ewout W , Numans Mattijs E , Kiefte-de Jong Jessica C 
Published: February 2022

ObjectivesThe aim of this study was to examine the added value of food insecurity in explaining poor physical and mental health beyond other socioeconomic risk factors.Design, setting, participants and outcome measuresData for this cross-sectional study were collected using questionnaires with validated measures for food insecurity status and health status, including 199 adult participants with at least 1 child living at home, living in or near disadvantaged neighbourhoods in The Hague, the Netherlands. To assess the added value of food insecurity, optimism-corrected goodness-of-fit statistics of multivariate regression models with and without food insecurity status as a covariate were compared.ResultsIn the multivariable models explaining poor physical health (Physical Component Summary: PCS) and mental health (Mental Component Summary: MCS), from all included socioeconomic risk factors, food insecurity score was the most important covariate. Including food insecurity score in those models led to an improvement of explained variance from 6.3% to 9.2% for PCS, and from 5.8% to 11.0% for MCS, and a slightly lower root mean square error. Further analyses showed that including food insecurity score improved the discriminative ability between those individuals most at risk of poor health, reflected by an improvement in C-statistic from 0.64 (95% CI 0.59 to 0.71) to 0.69 (95% CI 0.62 to 0.73) for PCS and from 0.65 (95% CI 0.55 to 0.68) to 0.70 (95% CI 0.61 to 0.73) for MCS. Further, explained variance in these models improved with approximately one-half for PCS and doubled for MCS.ConclusionsFrom these results it follows that food insecurity score is of added value in explaining poor physical and mental health beyond traditionally used socioeconomic risk factors (ie, age, educational level, income, living situation, employment status and migration background) in disadvantaged communities. Therefore, routine food insecurity screening may be important for effective risk stratification to identify populations at increased risk of poor health and provide targeted interventions.
Combined online interactive mindfulness and exercise programme (MOVE-Online) compared with a self-management guide for adults with chronic pain: protocol for a randomised controlled feasibility trial
Authors: Deegan Orla , Fullen Brona M , Casey Maire-Brid , Segurado Ricardo , Hearty Conor , Doody Catherine M 
Published: February 2022

IntroductionOnline pain management programmes (PMP) have growing evidence as effective interventions for individuals with chronic pain (CP). Mindfulness-based stress reduction (MBSR) is a psychological intervention proven to be effective in the management of CP. There is also a large body of evidence for the efficacy of exercise in the management of CP however, there are limited studies combining both these interventions and none to date delivering a combined intervention in the form of an online PMP. This study aims to explore the acceptability and feasibility of delivering a combined MBSR and exercise online PMP for adults with CP, and will examine the feasibility of conducting a randomised controlled trial of a combined MBSR and exercise online programme compared with an online self-management guide.Methods and analysisA parallel-group, feasibility randomised controlled trial (RCT) will be conducted among participants in Ireland, which will include an embedded qualitative study. Seventy-five participants will complete an online consent form and be individually randomised to one of two groups. Group A will participate in live online MBSR and supervised exercise sessions (2 hours MBSR, 1 hour exercise) once a week for 8 weeks. Group B will receive access to an 8-week online self-management guide, released biweekly and containing eight self-directed modules. Analyses of the feasibility study will be descriptive and will address the outcomes relating to the feasibility and acceptability of the interventions and procedures of the study including recruitment and eligibility, data collection methods, intervention adherence, engagement and attrition rates, intervention acceptability and participants’ subjective perceptions of the programmes. Comparisons of clinical treatment effects, using validated patient-reported outcome measures will be explored descriptively to consider the viability of investigating a combined online MBSR and exercise intervention in a future fully powered RCT.Ethics and disseminationThis study was approved by the Mater Misericordiae University Hospital Institutional Review Board (1/378/2124) and the University College Dublin Human Research Ethics Committee (LS-20-76-Deegan-Doody). Informed consent will be obtained from each participant prior to randomisation. The results of this feasibility study will be published in peer-reviewed academic journals and presented at national and international conferences.Trial registrationNCT04899622.
PAD-2-mediated citrullination of nucleophosmin provides an effective target for tumor immunotherapy
Authors: Choudhury Ruhul H , Symonds Peter , Paston Samantha J , Daniels Ian , Cook Katherine W , Gijon Mohamed , Metheringham Rachael L , Brentville Victoria A , Durrant Lindy G 
Published: February 2022

BackgroundThe enzymatic conversion of arginine to citrulline is involved in gene and protein regulation and in alerting the immune system to stressed cells, including tumor cells. Nucleophosmin (NPM) is a nuclear protein that plays key roles in cellular metabolism including ribosome biogenesis, mRNA processing and chromatin remodeling and is regulated by citrullination. In this study, we explored if the same citrullinated arginines within NPM are involved in gene regulation and immune activation.MethodsHLA-DP4 and HLA-DR4 transgenic mice were immunized with 22 citrullinated NPM overlapping peptides and immune responses to the peptides were assessed by ex vivo ELISpot assays. Antitumor immunity of NPM targeted vaccination was assessed by challenging transgenic mice with B16F1 HHDII/iDP4, B16F1 HHDII/PAD2KOcDP4, B16F1 HHDII and Lewis lung carcinoma cells/cDP4 cells subcutaneously. Peripheral blood mononuclear cells isolated from healthy donors were stimulated with NPM266-285cit peptides with/without CD45RO+memory cell depletion to assess if the responses in human were naïve or memory.ResultsIn contrast to NPM regulation, which is mediated by peptidylarginine deiminase (PAD4) citrullination of arginine at position 197, only citrullinated NPM266-285 peptide induced a citrulline-specific CD4 T cell response in transgenic mice models expressing human HLA-DP4 or HLA-DR4. Vaccinations with the NPM266-285cit peptide stimulated antitumor responses that resulted in dramatic tumor therapy, greatly improved survival, and protected against rechallenge without further vaccination. The antitumor response was lost if MHCII expression on the tumor cells was knocked out demonstrating direct presentation of the NPM266-285cit epitope in tumors. This antitumor response was lost in B16 tumors lacking PAD2 enzyme indicating NPM266cit is citrullinated by PAD2 in this model. Assessment of the T cell repertoire in healthy individuals and patients with lung cancer also showed CD4 T cells that respond to NPM266-285cit. The proliferative CD4 responses displayed a Th1 profile as they were accompanied with increased IFNγ and granzyme B expression. Depletion of CD45RO+ memory cells prior to stimulation suggested that responses originated from a naïve population in healthy donors.ConclusionThis study indicates PAD2 can citrullinate the nuclear antigen NPM at position 277 which can be targeted by CD4 T cells for antitumor therapy. This is distinct from PAD4 citrullination of arginine 197 within NPM which results in its transport from the nucleoli to the nucleoplasm.
Understanding the dynamics of notification and implementation of Article 5.3 across India’s states and union territories
Authors: Bassi Shalini , Ralston Rob , Arora Monika , Chugh Aastha , Nazar Gaurang P , Collin Jeff 
Published: February 2022

IntroductionIn federal systems, state and local governments may offer opportunities for innovation in implementing the WHO Framework Convention on Tobacco Control (FCTC). This paper explores the implementation of WHO FCTC Article 5.3 within India’s federal system, examining how its guidelines have been operationalised across states and union territories.MethodsInterviews with officials from government and civil society organisations across key states, and a document review of state government and district administration notifications adopting Article 5.3 guidelines between 2015 and 2019.ResultsThe data reveal subnational leadership in formulating intersectoral committees, which are designed to limit interactions with the tobacco industry, and corresponding measures to reject partnership and conflicts of interest for government officials. There are notable omissions across states and union territories in adoption of key Article 5.3 guidelines; only four districts and state governments refer to regulating aspects of ‘socially responsible’ industry activities, and no notifications include measures to prevent the tobacco industry receiving preferential treatment or requiring that information provided by industry actors be transparent and accountable. Interview data indicate that dynamics of notification across states have been shaped by lesson drawing and the catalytic role of civil society. The adoption of protocols is impacting on the practices of health officials, but there are concerns about engagement by other departments and the regulatory capacity of empowered committees.ConclusionThe spread of state- and district-level policies illustrates opportunities federal structures can provide for accelerating tobacco control. Given significant omissions and policy tensions, there remains a need for national action to build on these innovations, including in revisions to India’s tobacco control legislation.
A Comparison of Outcomes at Twelve Weeks of Traditional Button-Over-Nail versus Bone Anchor Repair of Zone I Flexor Digitorum Profundus Tendon Injury
Authors: PAYNE Anna , SAWHNEY Akshat , THACOOR Amitabh , AKHAVANI Mo 
Published: February 2022

Background: The repair of zone 1 flexor tendon injury often relies on re-inserting the flexor digitorum profundus (FDP) tendon to the distal phalanx. The aim of this retrospective study is to compare outcomes at 12 weeks following traditional button-over-nail (BON) versus bone anchor (BA) repair of zone I FDP injury. Methods: Patients undergoing zone 1 FDP repair between April 2007 and September 2018 using a BON or a BA were included in the study. Patient demographics, complications, arc of flexion of distal (distal interphalangeal joint [DIPJ]) and proximal interphalangeal joint (PIPJ) and patient-rated outcomes were analysed. Results: Forty-three patients were included in the study: 21 in the BA group and 22 in the BON group. Good function was achieved by 20 patients in BA versus nine in BON. Complications occurred in five BA patients versus 10 BON patients. Patients achieved a mean active DIPJ flexion of 49° and 31° and PIPJ flexion of 92° and 57° in the BA and BON groups, respectively. Conclusion: Our study demonstrates better arc of motion, patient-rated outcomes and lower complications at 12 weeks after surgery in patients undergoing zone 1 FDP repair using a BA. Level of Evidence: Level III (Therapeutic)