bluuebunny/crossref_metadata_2025_split huggingface dataset:
Vagus nerve stimulation as a novel treatment for systemic lupus erythematous: study protocol for a randomised, parallel-group, sham-controlled investigator-initiated clinical trial, the SLE-VNS study
Authors: Zinglersen Amanda Hempel , Drange Ida Lynghøj , Myhr Katrine Aagaard , Fuchs Andreas , Pfeiffer-Jensen Mogens , Brock Christina , Jacobsen Søren 
Published: September 2022

IntroductionSystemic lupus erythematosus (SLE) is a chronic autoimmune disease. SLE is treated with immunosuppressants with suboptimal efficacy and high risk of serious side effects. Patients with SLE have increased risk of mortality, organ damage and debilitating treatment-resistant fatigue. Autonomic nervous system dysfunction (AD) is present in approximately half of the patients and may promote autoimmunity by weakening the vagally mediated anti-inflammatory reflex. Recent studies suggest that transcutaneous vagus nerve stimulation (tVNS) has few side effects and beneficial effects on fatigue, pain, disease activity and organ function. This study investigates whether adjuvant tVNS improves measures of fatigue (primary end point), AD, clinical disease activity, inflammation, pain, organ function and quality of life.Hence, this study will contribute to the understanding of AD as a potentially important precursor of fatigue, disease activity, progression and complications in SLE, and how tVNS mechanistically may attenuate this. As adjuvant tVNS use may reduce the need for traditional immunosuppressive therapy, this trial may prompt a shift in the treatment of SLE and potentially other autoimmune disorders.Methods and analysisEighty-four patients with SLE with fatigue and AD will be randomised 1:1 to active or sham tVNS in this double-blinded parallel-group study. In period 1 (1 week), participants will receive a 4 min tVNS 4 times daily and report on fatigue daily. After a 2-week pause, period 2 (8 weeks) will entail tVNS twice daily and participants will report on fatigue, pain and disease activity weekly. Secondary end points will be assessed before and after each period and after 1 week in period 2.Ethics and disseminationThe study is approved by the Danish Medical Research Ethical Committees (case no: 2120231) and results will be published in international peer-reviewed journals.Trial registration numberNCT05315739.
Trends in dental visits during the state of emergency for COVID-19 in Japan: a retrospective observational study
Authors: Takeda Asuka , Tomio Jun , Fukuda Hideki , Ando Yuichi , Yokoyama Tetsuji 
Published: September 2022

ObjectivesTo determine national medium-term trends in dental visits during three COVID-19 emergency declaration periods in Japan and to analyse how these trends varied according to prefectural emergency measures and COVID-19 incidence.Design and settingA retrospective observational study of Japan’s dental claims from January 2017 to December 2021.Data sourcesData from a monthly report by the Health Insurance Claims Review and Reimbursement Services (HICRRS) in Japan. HICRRS handles the claims of employer-based health insurance.Data analysisWe determined the number of monthly dental claims nationwide from January 2017 to December 2021 and the percentage change in the number of monthly dental claims based on the difference in the COVID-19 alert level between the three emergency declaration periods in 2020–2021 and the corresponding periods in 2019. Results were analysed using descriptive statistics, multiple regression model, graphical figures, and narrative synthesis.Outcome measuresThe main outcome was the change in the number of dental visits between the emergency declaration periods in 2020–2021 and the corresponding periods in 2019. We also assessed the difference in the number of dental visits based on the COVID-19 alert level.ResultsThe data set included a total of 736 946 088 dental claims. Until the end of 2021, the greatest decrease in monthly dental claims was in April 2020, which was 22.3% lower than that in April 2019. As indicated by the coefficient in the regression model, the percentage change in monthly dental claims decreased by 5.01% (95% CI −8.27 to –1.74) depending on the difference between the prefectures designated as being under special precautions and other prefectures.ConclusionsThe decrease in dental visits was greater during the first state of emergency, ie, April–May 2020, and in prefectures designated as being under special precautions. Further efforts to promote appropriate dental visits at different alert levels are necessary.
Cohort profile: life with neurofibromatosis 1 – the Danish NF1 cohort
Authors: Doser Karoline , Hove Hanne , Østergaard John R , Bidstrup Pernille E , Dalton Susanne O , Handrup Mette Møller , Ejerskov Cecilie , Krøyer Anja , Doherty Mia Aagaard , Møllegaard Jepsen Jens Richardt , Mulvihill John J , Winther Jeanette F , Kenborg Line 
Published: September 2022

PurposeThe Danish neurofibromatosis 1 (NF1) cohort was initiated to study health-related, socioeconomic and psychological consequences of living with the monogenetic disorder NF1 using a nationwide and population-based approach.ParticipantsThe cohort includes all 2467 individuals in Denmark who were hospitalised with or due to NF1 from 1977 to 2013 or registered in the RAREDIS Database (1995–2013), a national clinical database for rare diseases, or both. A comparison cohort matched to individuals with NF1 on sex and date of birth was identified in the Civil Registration System (n=20 132).Findings to dateAll cohort members were linked to the unique Danish registries to obtain information on hospital contacts, birth outcomes, education and partnership. A questionnaire was completed by 244 of the 629 adult cohort members with NF1 registered in the RAREDIS Database to evaluate the psychosocial and emotional burden. Further, neuropsychological tests were performed on 103 adult cohort members with NF1 and 38 adult population comparisons. To date, six studies have been published. Individuals with NF1 had an increased risk for (1) hospitalisation for disorders affecting all organ systems of the body throughout all decades of life, (2) psychiatric disorders, (3) attaining a short or medium long education and (4) not forming a life partner. Women with NF1 had an increased risk for spontaneous abortions and stillbirths. Finally, adults with NF1 had an impaired quality of life and a high need for professional support for physical, psychological and work-related problems, which was partly associated with disease severity and visibility.Future plansThe cohort will regularly be updated with newly diagnosed patients in the RAREDIS Database as well as with outcome information in the Danish registries. New studies are in progress to assess other medical and socioeconomic dimensions of living with NF1.
Nursing contributions to virtual models of care in primary care: a scoping review protocol
Authors: Vaughan Crystal , Lukewich Julia , Mathews Maria , Hedden Lindsay , Poitras Marie-Eve , Asghari Shabnam , Swab Michelle , Ryan Dana 
Published: September 2022

IntroductionSince the onset of the COVID-19 pandemic, virtual care has gained increased attention, particularly in primary care for the ongoing delivery of routine services. Nurses have had an increased presence in virtual care and have contributed meaningfully to the delivery of team-based care in primary care; however, their exact contributions in virtual models of primary care remain unclear. The Nursing Role Effectiveness Model, applied in a virtual care and primary care context, outlines the association between structural variables, nursing roles and patient outcomes. The aim of this scoping review is to identify and synthesise the international literature surrounding nurse contributions to virtual models of primary care.Methods and analysisThe Joanna Briggs Institute scoping review methodology will guide this review. We performed preliminary searches in April 2022 and will use CINAHL, MEDLINE, Embase and APA PsycInfo for the collection of sources for this review. We will also consider grey literature, such as dissertations/theses and organisational reports, for inclusion. Studies will include nurses across all designations (ie, nurse practitioners, registered nurses, practical nurses). To ensure studies capture roles, nurses should be actively involved in healthcare delivery. Sources require a virtual care and primary care context; studies involving the use of digital technology without patient–provider interaction will be excluded. Following a pilot test, trained reviewers will independently screen titles/abstracts for inclusion and extract relevant data. Data will be organised using the Nursing Role Effectiveness Model, outlining the virtual care and primary care context (structure component) and the nursing role concept (process component).Ethics and disseminationThis review will involve the collection and analysis of secondary sources that have been published and/or are publicly available. Therefore, ethics approval is not required. Scoping review findings will be published in a peer-reviewed journal and presented at relevant conferences, targeting international primary care stakeholders.
External validation of the ProVent score for prognostication of 1-year mortality of critically ill patients with prolonged mechanical ventilation: a single-centre, retrospective observational study in Austria
Authors: Dibiasi Christoph , Kimberger Oliver , Bologheanu Razvan , Staudinger Thomas , Heinz Gottfried , Zauner Christian , Sengölge Gürkan , Schaden Eva 
Published: September 2022

ObjectivesIn critically ill patients requiring mechanical ventilation for at least 21 days, 1-year mortality can be estimated using the ProVent score, calculated from four variables (age, platelet count, vasopressor use and renal replacement therapy). We aimed to externally validate discrimination and calibration of the ProVent score and, if necessary, to update its underlying regression model.DesignRetrospective, observational, single-centre study.Setting11 intensive care units at one tertiary academic hospital.Patients780 critically ill adult patients receiving invasive mechanical ventilation for at least 21 days.Primary outcome measure1-year mortality after intensive care unit discharge.Results380 patients (49%) had died after 1 year. One-year mortality for ProVent scores from 0 to 5 were: 15%, 27%, 57%, 66%, 72% and 76%. Area under the receiver operating characteristic curve of the ProVent probability model was 0.76 (95% CI 0.72 to 0.79), calibration intercept was −0.43 (95% CI −0.59 to −0.27) and calibration slope was 0.76 (95% CI 0.62 to 0.89). Model recalibration and extension by inclusion of three additional predictors (total bilirubin concentration, enteral nutrition and surgical status) improved model discrimination and calibration. Decision curve analysis demonstrated that the original ProVent model had negative net benefit, which was avoided with the extended ProVent model.ConclusionsThe ProVent probability model had adequate discrimination but was miscalibrated in our patient cohort and, as such, could potentially be harmful. Use of the extended ProVent score developed by us could possibly alleviate this concern.
New dual dye for vitreoretinal surgery with increased transparency
Authors: Mohr Andreas , Cendoya Paula , Wilinska Joanna , Apostu Maria , Apostu Elena , Janku Jori , Wilfling Tom , Ramos Gabriela , Al-Joumhawy Mahmoud , Gabel Detlef 
Published: September 2022

ObjectivesTo develop a new dye formulation for vitreoretinal surgery, which shows increased transparency for better intraoperative handling with better parameters important for use.Methods and analysisA new blue dye, DDG, was synthesised and tested for toxicity and staining. Diglycerol as new density-increasing additive was identified, and its toxicity and lack of influence of the staining with trypan blue (TB) on a collagen membrane as model for the epiretinal membrane was determined. Transparency of the dye solution was evaluated.ResultsDDG is as alternative to Brilliant Blue G (BBG), with good staining properties for interna limitans models, and a good safety profile. Diglycerol is a new non-toxic additive replacing PEG3350, with reduced viscosity and no reduction in staining, allowing the reduction of TB to achieve the same staining level of the collagen membrane by 40%, with greater transparency of the dye solution and reduced viscosity. Both factors should facilitate a safe removal during surgery.ConclusionA new dye preparation with improved performance in comparison to marketed combinations of BBG and TB was developed. Its reduced TB concentration and viscosity with maintained density allow better tolerance and handling.
CDC20 May Serve as a Potential Biomarker-Based Risk Score System in Predicting the Prognosis of Patients with Hepatocellular Carcinoma
Authors: Peng Qiliu , Huang Hai , Zhu Chunling , Hou Qingqing , Wei Shangmou , Xiao Yi , Zhang Zhi , Sun Xing 
Published: September 2022

Background. The specificity and sensitivity of hepatocellular carcinoma (HCC) diagnostic markers are limited, hindering the early diagnosis and treatment of HCC patients. Therefore, improving prognostic biomarkers for patients with HCC is urgently needed. Methods. HCC-related datasets were downloaded from the public databases. Differentially expressed genes (DEGs) between HCC and adjacent nontumor liver tissues were then identified. Moreover, the intersection of DEGs in four datasets (GSE138178, GSE77509, GSE84006, and TCGA) was used in the functional enrichment, and module genes were obtained by a coexpression network. Cox and Kaplan-Meier analyses were used to identify overall survival- (OS-) related genes from module genes.

Area

under

the

curve

AUC

>
0.9

of OS-related genes was then carried out in order to perform the protein-protein interaction network. The feature genes were identified by least absolute shrinkage and selection operator (LASSO). Furthermore, the hub gene was identified through the univariate Cox model, after which the correlation analysis between the hub gene and pathways was explored. Finally, infiltration in immune cell types in HCC was analyzed. Results. A total of 2,227 upregulated genes and 1,501 downregulated DEGs were obtained in all four datasets, which were mainly found to be involved in the cell cycle and retinol metabolism. Accordingly, 998 OS-related genes were screened to construct the LASSO model. Finally, 8 feature genes (BUB1, CCNB1, CCNB2, CCNA2, AURKB, CDC20, OIP5, and TTK) were obtained. CDC20 was shown to serve as a poor prognostic gene in HCC and was mainly involved in the cell cycle. Moreover, a positive correlation was noted between the high degree of infiltration with Th2 and CDC20. Conclusion. High expression of CDC20 predicted poor survival, as potential target in the treatment for HCC.
Proteomic Analysis of Effects of Spironolactone in Heart Failure With Preserved Ejection Fraction
Authors: Javaheri Ali , Diab Ahmed , Zhao Lei , Qian Chenao , Cohen Jordana B. , Zamani Payman , Kumar Anupam , Wang Zhaoqing , Ebert Christina , Maranville Joseph , Kvikstad Erika , Basso Michael , van Empel Vanessa , Richards A. Mark , Doughty Robert N. , Rietzschel Ernst , Kammerhoff Karl , Gogain Joseph , Schafer Peter , Seiffert Dietmar A. , Gordon David A. , Ramirez-Valle Francisco , Mann Douglas L. , Cappola Thomas P. , Chirinos Julio A. 
Published: September 2022

Background:
The TOPCAT trial (Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist Trial) suggested clinical benefits of spironolactone treatment among patients with heart failure with preserved ejection fraction enrolled in the Americas. However, a comprehensive assessment of biologic pathways impacted by spironolactone therapy in heart failure with preserved ejection fraction has not been performed.

Methods:
We conducted aptamer-based proteomic analysis utilizing 5284 modified aptamers to 4928 unique proteins on plasma samples from TOPCAT participants from the Americas (n=164 subjects with paired samples at baseline and 1 year) to identify proteins and pathways impacted by spironolactone therapy in heart failure with preserved ejection fraction. Mean percentage change from baseline was calculated for each protein. Additionally, we conducted pathway analysis of proteins altered by spironolactone.

Results:

Spironolactone therapy was associated with proteome-wide significant changes in 7 proteins. Among these, CARD18 (caspase recruitment domain-containing protein 18), PKD2 (polycystin 2), and PSG2 (pregnancy-specific glycoprotein 2) were upregulated, whereas HGF (hepatic growth factor), PLTP (phospholipid transfer protein), IGF2R (insulin growth factor 2 receptor), and SWP70 (switch-associated protein 70) were downregulated. CARD18, a caspase-1 inhibitor, was the most upregulated protein by spironolactone (−0.5% with placebo versus +66.5% with spironolactone,
P
<0.0001). The top canonical pathways that were significantly associated with spironolactone were apelin signaling, stellate cell activation, glycoprotein 6 signaling, atherosclerosis signaling, liver X receptor activation, and farnesoid X receptor activation. Among the top pathways, collagens were a consistent theme that increased in patients receiving placebo but decreased in patients randomized to spironolactone.

Conclusions:
Proteomic analysis in the TOPCAT trial revealed proteins and pathways altered by spironolactone, including the caspase inhibitor CARD18 and multiple pathways that involved collagens. In addition to effects on fibrosis, our studies suggest potential antiapoptotic effects of spironolactone in heart failure with preserved ejection fraction, a hypothesis that merits further exploration.
Impact of Sex and Cardiovascular Risk Factors on Myocardial T1, Extracellular Volume Fraction, and T2 at 3 Tesla: Results From the Population-Based, Hamburg City Health Study
Authors: Cavus Ersin , Schneider Jan N. , Bei der Kellen Ramona , di Carluccio Eleonora , Ziegler Andreas , Tahir Enver , Bohnen Sebastian , Avanesov Maxim , Radunski Ulf K. , Chevalier Celeste , Jahnke Charlotte , Ojeda Francisco , Kirchhof Paulus , Blankenberg Stefan , Adam Gerhard , Lund Gunnar K. , Muellerleile Kai 
Published: September 2022

Background:
Reliable reference intervals are crucial for clinical application of myocardial T1 and T2 mapping cardiovascular magnetic resonance imaging. This study evaluated the impact of sex and cardiovascular risk factors on myocardial T1, extracellular volume fraction (ECV), and T2 at 3T in the population-based HCHS (Hamburg City Health Study).

Methods:
The final study sample consisted of 1576 consecutive HCHS participants between 46 and 78 years without prevalent heart disease, including 1020 (67.3%) participants with hypertension and 110 (7.5%) with diabetes. T1 and T2 mapping were performed on a 3T scanner using 5b(3b)3b modified Look-Locker inversion recovery and T2 prepared, fast-low-angle shot sequence, respectively. Stepwise regression analyses were performed to identify variables with an independent impact on T1, ECV, and T2. Reference intervals were defined as the interval between the 2.5% and 97.5% quantiles.

Results:

Sex was the major independent influencing factor of myocardial native T1, ECV, and T2. Female patients had significantly higher upper limits of reference intervals for native T1 (1112–1261 versus 1079–1241 ms), ECV (23%–33% versus 22%–32%), and T2 (36–46 versus 35–45 ms) compared with male patients (all
P
<0.001). Cardiovascular risk factors, such as diabetes and hypertension, did not systematically affect native T1. There was an independent association of T2 by hypertension and, to a lesser degree, by left ventricular mass, heart rate (all
P
<0.001), and body mass index (
P
=0.001).

Conclusions:
Sex needs to be considered as the major, independent influencing factor for clinical application of myocardial T1, ECV, and T2 measurements. Consequently, sex-specific reference intervals should be used in clinical routine. Our findings suggest that there is no need for specific reference intervals for myocardial T1 and ECV measurements in individuals with cardiovascular risk factors. However, hypertension should be considered as an additional factor for clinical application of T2 measurements.

Registration:

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT03934957.
Auricular Malignant Proliferating Trichilemmal Tumor: A Case Report
Authors: Zhou Enhui , Xue Xiaocheng , Liu Xing , Zhang Yi 
Published: September 2022

Malignant proliferating trichilemmal tumor (MPTT) is a dermal adnexal tumor originated from the external root sheath of hair follicles. In this article, we reported a rare case of auricular MPTT in a 65-year-old male with gradually enlarging and bleeding mass on the right auricle measuring 30 × 20 × 12 mm in size and detailed the surgical strategy for therapy. The diagnosis of MPTT was established primarily by histopathological observation with abrupt keratinization, cytological atypia, abnormal mitoses, and infiltrating margins. Following extensive excision, no recurrence was noted for 14 months. We also discuss its clinicopathological features, differential diagnoses, and treatment methods and review the relevant literature in this regard.
Elevated alanine aminotransferase is associated with biphasic insulin secretion in the healthy elderly Han Chinese population
Authors: Wu Tzong-Yow , Liao En-Chih , Chen Yen-Lin , Lin Yung-Feng , Liu Shu-Hsiang , Lin Hua-Ching , Chiu Yi-Chou , Wu Chung-Ze , Lin Jiunn-Diann , Pei Dee , Hsu Chun-Hsien 
Published: September 2022

Objective To evaluate the relationship between alanine transaminase (ALT) level and biphasic insulin secretion (BPIS) in healthy elderly Han Chinese individuals. Methods This cross-sectional study enrolled healthy elderly participants aged ≥60 years that were part of a health examination programme. In order to explore the correlation and severity of the clinical condition, those with any possible confounding factors known to affect insulin secretion or liver function were excluded from the study. BPIS was calculated using an equation developed previously by this research team. Results This study enrolled 39 845 healthy elderly individuals (19 058 males and 20 787 females). Participants were stratified into four quartile groups according to their ALT level. In both males and females, the increasing ALT quartiles (ordinal variable) were associated with greater values of log-transformed first-phase insulin secretion (FPIS) and second-phase insulin secretion (SPIS). The correlation and the linear regression model showed that increasing ALT level was significantly correlated with higher log-transformed FPIS and SPIS. Conclusions ALT was positively correlated with BPIS in a healthy elderly population in both men and women. Elevated ALT may serve as an indicating factor for developing metabolic syndrome and type 2 diabetes mellitus in healthy elderly individuals.