bluuebunny/crossref_metadata_2025 huggingface dataset:
Differences in circulating cardiac troponin I and T in acute and chronic cardiac disease
Authors: Zimmermann T , Koechlin L , Walter J , Kimenai D , Nestelberger T , Boeddinghaus J , Lopez-Ayala P , Puelacher C , Gualandro D , Strebel I , Diebold M , Twerenbold R , Hammarsten O , Meex S , Mueller C
Published: October 2022

Background

Clinical practice and guidelines assume that cardiac troponin I (cTnI) and cTnT are interchangeable, reflecting identical pathophysiological processes. However, it is unknown if cTnI and cTnT really are equivalent measures in different pathophysiological settings.

Purpose

To highlight potential differences in the release of cTnI and cTnT.

Methods

Large pooled cohort analysis including extensively characterized individuals, stratified into three groups: no cardiac disease (normal aging), chronic cardiac disease, and acute cardiac disease. Circulating cTnI and cTnT concentrations were measured blinded to clinical data using high-sensitivity assays (hs-cTnI-Architect, hs-cTnT-Elecsys) and their ratio calculated. Findings were validated using a second hs-cTnI assay (hs-cTnI-Clarity).

Results

Among 8719 individuals, 29% female, 10% had no known cardiac disease, 71% chronic cardiac disease, and 20% acute cardiac disease. Baseline characteristics including renal function were comparable between individuals with chronic and acute cardiac disease. Normal aging (without cardiac disease) was associated with a disproportional increase in cTnT versus cTnI (low cTnI/cTnT ratio, median 0.50, IQR 0.38–0.68). Although older, patients with chronic cardiac disease had a slightly higher cTnI/cTnT ratio (median 0.53, IQR 0.37–0.79, p<0.05). In contrast, in patients with acute cardiac disease, cTnI concentrations were disproportionally elevated compared to cTnT concentrations, resulting in a cTnI/cTnT ratio of 1.96 (IQR 0.93–4.73, p<0.001). Internal validation using a second hs-cTnI assay confirmed these findings.

Conclusion

These findings suggest relevant differences in the release of cTnI and cTnT with a greater release of cTnT versus cTnI in normal aging and a disproportional increase in cTnI versus cTnT in acute cardiac disease.

Funding Acknowledgement

Type of funding sources: Foundation. Main funding source(s): Swiss National Science Foundation
Agreement between four high-sensitivity cardiac troponin assays and non-invasive testing, clinical and quality of care outcomes based on the 2020 ESC guidelines: results from the ROMICAT II trial
Authors: Karady J , Mayrhofer T , Nagurney J T , Udelson J E , Fleg J L , Peacock W F , Januzzi J L , Koenig W , Ferencik M , Hoffmann U
Published: October 2022

Background

Quality of care and safety of patients with suspected acute coronary syndrome (ACS) would greatly benefit if management was independent of which high-sensitivity cardiac troponin (hs-cTn) assay was used for risk stratification.

Purpose

To assess the agreement of 4 hs-cTn assays to risk stratify patients with suspected ACS using the ESC2020 Guidelines 0/2-hour algorithm, and to assess their associations with non-invasive diagnostic testing, clinical- and quality of care outcomes.

Methods

We analyzed blood samples obtained at emergency department (ED) presentation and 2 hours later from patients with suspected ACS enrolled in the ROMICAT (Rule Out Myocardial Infarction/Ischemia Using Computer Assisted Tomography) II trial, using 4 hs-cTn assays (Roche Diagnostics, Elecsys 2010; Abbott Diagnostics, ARCHITECT i2000SR; Siemens Diagnostics, HsVista; Beckman Coulter, ACCESS). We determined the agreement between the assays to assign patients to rule-out, observe, and rule-in management pathways according to the ESC2020 Guidelines. Further, we assessed assay association with non-invasive diagnostic test findings and adjudicated clinical- and quality of care outcomes. Finally, we compared observed conventional troponin management with predicted management per ESC2020 guidelines using hs-cTn assays.

Results

Overall, assignment to ESC2020 Guideline management pathways among 238 patients with suspected ACS (age 52.7±8.0 years; 40.3% [96/238] female) was concordant across all hs-Tn assays in 74% of patients but differed for rule-out rates (89.9% vs 76.5% vs 78.6% vs 86.6%, p<0.001) and observation rates (6.7% vs 20.6% vs 17.7% vs 9.2%, p<0.001), but not for rule-in (3.4% vs 2.9% vs 3.8% vs 4.2%, p=0.623). Among those whose management recommendation was rule-out, 19.1–21.6% had obstructive CAD defined as coronary stenosis ≥50% on coronary CT angiography or inducible myocardial ischemia on perfusion imaging and 3.3–4.2% were diagnosed with ACS as adjudicated by independent panel. Predicted ED discharge rates based on hs-cTn assays were higher than those observed with conventional troponin (80.3% to 90.8% vs. 21.0%, respectively p<0.001). As a result, predicted costs of care were significantly lower based on strategies utilizing hs-cTn assays than with conventional troponin ($2,578±2,896 to $2,894±4,371 vs $3,889±4,833, respectively, p<0.001)

Conclusion

In a quarter of patients presenting to the ED with suspected ACS ESC2020 Guideline-based management may be different, depending on the hs-cTn assay. As compared to conventional troponin, hs-cTn is predicted to significantly increase direct ED discharges and lower costs of care.

Funding Acknowledgement

Type of funding sources: None.
An altered balance of plasma arginine metabolites is associated with increased thickness of the coronary intima-media complex in the adjacent to the culprit segment of an infarct-related artery
Authors: Molek P , Zmudzki P , Machnik A , Nowak G , Wnuk M , Wlodarczyk A , Nessler J , Zalewski J
Published: October 2022

Background

The biomarkers of atherosclerosis remain insufficiently understood.

Purpose

We sought to investigate whether an altered balance of arginine metabolites in patients following myocardial infarction (MI) is associated with remodeling of the adjacent to the culprit segments of an infarct-related artery (IRA) and with clinical outcomes.

Methods

Arginine and its metabolites including ornithine, citrulline, proline and asymmetric dimethylarginine were measured using liquid chromatography and tandem mass spectrometry in 85 consecutive ST-segment elevation MI patients upon admission and at 6-month follow-up and were compared with morphology of the adjacent to the culprit proximal and distal 10-mm segments of IRA assessed with optical coherence tomography. A composite ischemic event was defined as death, recurrent MI, stroke, or unplanned percutaneous coronary intervention.

Results

The ratios of citrulline/ornithine and citrulline/arginine decreased 5.22 and 2.20 times (both P<0.001) respectively, while the ornithine/arginine index (I_O/A) increased 2.96 times (P<0.001) following ischemia compared with stable follow-up, indicating the enhanced arginase activity over nitric oxide synthase (NOS) in acute phase of STEMI. Follow-up I_O/A correlated with the mean intima-media (R=0.34, P=0.003, Figure 1A) and intima (R=0.30, P=0.008) diameter of an adjacent to the culprit IRA segment. By multivariate analysis, apart from male gender (P<0.001) and diabetes mellitus (P=0.02), a higher follow-up I_O/A was associated with the larger mean intima-media diameter of an adjacent to the culprit IRA segments (coefficient 0.218, 95% confidence interval 0.040–0.397, P=0.017, per 0.01). Within the median follow-up of 25 (19–35) months, ischemic composite endpoint was found in 13 (15.3%) patients. The follow-up I_O/A reached the area under the ROC curve of 0.78 (95% confidence interval 0.66–0.91, P=0.005) for prediction of composite ischemic endpoint with a cut-off value of ≥0.57, and a sensitivity of 72.3% and specificity of 80.0% (Figure !B).

Conclusions

Our findings provide arguments that during the acute phase of MI, arginine metabolism is shifted from NOS towards arginase, as compared to 6-month stable conditions. Simultaneously, the enhanced residual arginase activity over NOS in chronic phase was correlated with a higher thickness of intima or intima-media in the adjacent to the culprit segment within the IRA, and was also associated with unfavorable clinical outcomes.

Funding Acknowledgement

Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Grant of the National Science Center of Poland (Number 2016/21/B/NZ5/01378 to J.Z.)
Validation of a novel high-sensitivity cardiac troponin assay
Authors: Restan I , Steiro O T , Tjora H L , Langoergen J , Omland T , Collinson P , Bjoerneklett R , Vikenes K , Steinsvik T , Skadberg O , Mjelva O R , Larsen A I , Bonarjee V S , Aakre K M
Published: October 2022

Background

The accuracy for early identification of non-ST-elevation myocardial infarction (NSTEMI) in the emergency department must be determined for all novel high-sensitivity cardiac troponin assays (hs-cTn). In this prospective, multi-centre study we developed rule-out algorithms for a high-sensitivity cardiac troponin I (hs-cTnI) assay and compared it to established algorithms for hs-cTnT and hs-cTnI.

Methods

Two rule-out algorithms for NSTEMI were developed from a derivation cohort of 977 patients assessed by the Siemens Atellica IM hs-cTnI assay. Diagnostic performance was compared with hs-cTnT (Roche) and hs-cTnI (Abbott) algorithms. The derived algorithms were tested in two different validation cohorts (n=518 and n=405, respectively).

Results

An admission sample algorithm (hs-cTnI (Siemens)) for rule-out of NSTEMI with cutoff <5 ng/L had negative predictive value (NPV) 99.4–100.0%, sensitivity 98.3–100% and specificity 46.7–56.5% in the two validation cohorts. Sensitivity and NPV was similar, specificity trended towards improvement over the comparator algorithms (Figure 1).

A 0–1 hour algorithm (hs-cTnI (Siemens)) with cutoff <10 ng/L and Δ change <3 ng/L achieved sensitivity and NPV 100% with specificity >70% in both validation cohorts, similar to the comparator algorithms (Table 1).

Conclusions

Rule-out algorithms from the Siemens Atellica hs-cTnI assay has comparable diagnostic accuracy to established hs-cTn rule-out algorithms.

Funding Acknowledgement

Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Public grant: Western Norway Regional Health Authority.Private company funding: Siemens Healthineers AG
Effectiveness of antitussives, anticholinergics, and honey versus usual care in adults with uncomplicated acute bronchitis: a multiarm randomized clinical trial
Authors: Llor Carl , Moragas Ana , Ouchi Dan , Monfà Ramon , Garcia-Sangenís Ana , Gómez-Lumbreras Ainhoa , Pera Helena , Pujol Jesus , Morros Rosa
Published: October 2022

Background

Despite the frequent use of symptomatic therapies in cough, evidence of their benefits is lacking.

Objective

We compared the effectiveness of 3 symptomatic therapies and usual care in acute bronchitis.

Methods

Multicenter, pragmatic, multiarm parallel group, open randomized trial in primary care (ClinicalTrials.gov, Identifier: NCT03738917) was conducted in Catalonia. Patients ≥18 with uncomplicated acute bronchitis, with cough<3 weeks as the main symptom, scoring ≥4 in either daytime or nocturnal cough (7-point Likert scale), were randomized to usual care, dextromethorphan 15 mg t.i.d., ipratropium bromide inhaler 20 µg 2 puffs t.i.d, or 30 mg of honey t.i.d., all taken for up to 14 days. The main outcome measure was the number of days with moderate-to-severe cough. A symptom diary was given. A second visit was scheduled at days 2–3 for assessing evolution, with 2 more visits at days 15 and 29 for clinical assessment, evaluation of adverse effects, re-attendance, and complications.

Results

We failed to achieve the sample size scheduled due to the COVID-19 pandemic. We finally recruited 194 patients. The median number of days with moderate-to-severe cough (score ≥ 3) in the usual care arm was 5 (interquartile range [IQR], 4, 8.75), 5 in the ipratropium bromide arm (IQR, 3, 8), 5 in the dextromethorphan arm (IQR, 4, 9.75), and 6 in the honey arm (IQR, 3.5, 7). The same results were obtained in the Kaplan–Meier survival analysis for the median survival time of each arm with the usual care as the reference group.

Conclusion

The symptomatic treatment evaluated has shown to be ineffective against cough.
Microseismic data denoising in the sychrosqueezed domain by integrating the wavelet coefficient thresholding and pixel connectivity
Authors: Zeng Zhiyi , Lu Tianxin , Han Peng , Zhang Da , Yang Xiao-Hui , Shi Yaqian , Chang Ying , Zhang Jianzhong , Dai Rui , Ji Hu
Published: October 2022

Microseismic monitoring is crucial for risk assessment in mining, fracturing and excavation. In practice, microseismic records are often contaminated by undesired noise, which is an obstacle to high-precision seismic locating and imaging. In this study, we develop a new denoising method to improve the signal-to-noise ratio (SNR) of seismic signals by combining wavelet coefficient thresholding and pixel connectivity thresholding. First, the pure background noise range in the seismic record is estimated using the ratio of variance (ROV) method. Then, the synchrosqueezed continuous wavelet transform (SS-CWT) is used to project the seismic records onto the time–frequency plane. After that, the wavelet coefficient threshold for each frequency is computed based on the empirical cumulative distribution function (ECDF) of the coefficients of the pure background noise. Next, hard thresholding is conducted to process the wavelet coefficients in the time–frequency domain. Finally, an image processing approach called pixel connectivity thresholding is introduced to further suppress isolated noise on the time–frequency plane. The wavelet coefficient threshold obtained by using pure background noise data is theoretically more accurate than that obtained by using the whole seismic record, because of the discrepancy in the power spectrum between seismic waves and background noise. After hard thresholding, the wavelet coefficients of residual noise exhibit isolated and lower pixel connectivity in the time–frequency plane, compared with those of seismic signals. Thus, pixel connectivity thresholding is utilized to deal with the residual noise and further improve the SNR of seismic records. The proposed new denoising method is tested by synthetic and real seismic data, and the results suggest its effectiveness and robustness when dealing with noisy data from different acquisition environments and sampling rates. The current study provides a useful tool for microseismic data processing.
NRSF regulates age-dependently cognitive ability and its conditional knockout in APP/PS1 mice moderately alters AD-like pathology
Authors: Yang Yufang , Zhang Xiaoshuang , Li Dongxue , Fang Rong , Wang Zishan , Yun Di , Wang Mo , Wang Jinghui , Dong Hongtian , Fei Zhaoliang , Li Qing , Liu Zhaolin , Shen Chenye , Fei Jian , Yu Mei , Behnisch Thomas , Huang Fang
Published: October 2022

NRSF/REST (neuron-restrictive silencer element, also known as repressor element 1-silencing transcription factor), plays a key role in neuronal homeostasis as a transcriptional repressor of neuronal genes. NRSF/REST relates to cognitive preservation and longevity of humans, but its specific functions in age-dependent and Alzheimer’s disease (AD)-related memory deficits remain unclear. Here, we show that conditional NRSF/REST knockout either in the dorsal telencephalon or specially in neurons induced an age-dependently diminished retrieval performance in spatial or fear conditioning memory tasks and altered hippocampal synaptic transmission and activity-dependent synaptic plasticity. The NRSF/REST deficient mice were also characterized by an increase of activated glial cells, complement C3 protein and the transcription factor C/EBPβ in the cortex and hippocampus. Reduction of NRSF/REST by conditional depletion upregulated the activation of astrocytes in APP/PS1 mice, and increased the C3-positive glial cells, but did not alter the Aβ loads and memory retrieval performances of 6- and 12-month-old APP/PS1 mice. Simultaneously, overexpression of NRSF/REST improved cognitive abilities of aged wild type, but not in AD mice. These findings demonstrated that NRSF/REST is essential for the preservation of memory performance and activity-dependent synaptic plasticity during aging and takes potential roles in the onset of age-related memory impairments. However, while altering the glial activation, NRSF/REST deficiency does not interfere with the Aβ deposits and the electrophysiological and cognitive AD-like pathologies.
The effect on women’s health of extending parental leave: a quasi-experimental registry-based cohort study
Authors: Courtin Emilie , Rieckmann Andreas , Bengtsson Jessica , Nafilyan Vahe , Melchior Maria , Berkman Lisa , Hulvej Rod Naja
Published: October 2022

Background

Parental leave policies have been hypothesized to benefit mothers’ mental health. We assessed the impact of a 6-week extension of parental leave in Denmark on maternal mental health.

Methods

We linked individual-level data from Danish national registries on maternal sociodemographic characteristics and psychiatric diagnoses. A regression discontinuity design was applied to study the increase in parental leave duration after 26 March 1984. We included women who had given birth between 1 January 1981 and 31 December 1987. Our outcome was a first psychiatric diagnosis following the child’s birth, ascertained as the first day of inpatient hospital admission for any psychiatric disorder. We presented cumulative incidences for the 30-year follow-up period and reported absolute risk differences between women eligible for the reform vs not, in 5-year intervals.

Results

In all, 291 152 women were followed up until 2017, death, emigration or date of first psychiatric diagnosis. The median follow-up time was 29.99 years, corresponding to 10 277 547 person-years at risk. The cumulative incidence of psychiatric diagnoses at 30 years of follow-up was 59.5 (95% CI: 57.4 to 61.6) per 1000 women in the ineligible group and 57.5 (95% CI: 55.6 to 59.4) in the eligible group. Eligible women took on average 32.85 additional days of parental leave (95% CI: 29.20 to 36.49) and had a lower probability of having a psychiatric diagnosis within 5 years [risk difference (RD): 2.4 fewer diagnoses per 1000 women, 95% CI: 1.5 to 3.2] and up to 20 years after the birth (RD: 2.3, 95% CI: 0.4 to 4.2). In subgroup analyses, the risk reduction was concentrated among low-educated, low-income and single women.

Conclusions

Longer parental leave may confer mental health benefits to women, in particular to those from disadvantaged backgrounds.
RsCLE22a regulates taproot growth through an auxin signaling-related pathway in radish (Raphanus sativus L.)
Authors: Dong Junhui , Wang Yan , Xu Liang , Li Bingshuang , Wang Kai , Ying Jiali , He Qing , Liu Liwang
Published: October 2022

CLAVATA3/EMBRYO SURROUNDING REGION-related (CLE) peptides are a class of small molecules involved in plant growth and development. Although radish (Raphanus sativus) is an important root vegetable crop worldwide, the functions of CLE peptides in its taproot formation remain elusive. Here, a total of 48 RsCLE genes were identified from the radish genome. RNA in situ hybridization showed that RsCLE22a gene was highly expressed in the vascular cambium. Overexpression of RsCLE22a inhibited root growth by impairing stem cell proliferation in Arabidopsis, and radish plants with exogenous supplementation of RsCLE22 peptide (CLE22p) showed a similar phenotype. The vascular cambial activity was increased in RsCLE22a-silenced plants. Transcriptome analysis revealed that CLE22p altered the expression of several genes involved in meristem development and hormone signal transduction in radish. Immunolocalization results showed that CLE22p increased auxin accumulation in vascular cambium. Yeast one-hybrid and dual-luciferase assays showed that the WUSCHEL-RELATED HOMEOBOX 4 (RsWOX4) binds to RsCLE22a promoter and activates its transcription. The expression level of RsWOX4 was related to vascular cambial activity and was regulated by auxin. Furthermore, a RsCLE22a–RsWOX4 module is proposed to regulate taproot vascular cambium activity through an auxin signaling-related pathway in radish. These findings provide novel insights into the regulation of root growth in a horticultural crop.
Association of Interleukin-6 Polymorphisms with Schizophrenia and Depression: A Case-Control Study
Authors: Lu Danyu , Wang Minli , Yang Tongfei , Wang Jianyou , Lin Baiquan , Liu Guoyan , Liang Qiaoyan
Published: October 2022

Objective

Growing evidence suggests a crossover in genetic susceptibility to schizophrenia and depression. We aimed to investigate the association of the rs1800795 and rs1800796 polymorphisms of the IL-6 gene with schizophrenia and depression in the Han Chinese population, combined with IL-6 serum levels.

Methods

Gene sequencing and enzyme-linked immunosorbent assay were performed on 113 subjects with schizophrenia, 114 subjects with depression, and 110 healthy controls.

Results

Our findings showed that IL-6 concentrations in schizophrenia and depression groups were significantly higher than in the control group. The rs1800796 CC genotype and C allele were significantly associated with depression (P = .012 and P < .05, respectively). The rs1800796 CC and CG genotype was significantly associated with chronic schizophrenia (P = .020 and P = .009, respectively). Regarding the rs1800795 polymorphism, only one case of CG genotype was detected. The remainder were of the GG genotype.

Conclusion

The IL-6 rs1800796 might serve as a protective factor for depression and schizophrenia in the Han Chinese population.
Research Priorities Among Canadian Military Veterans Living With Chronic Pain: A Cross-Sectional Survey
Authors: Qureshi Abdul Rehman , Makanjuola Oluwatoni , Neumark Samuel , Garas Andrew , Wang Li , Busse Jason W
Published: October 2022

Introduction

Chronic pain is a debilitating problem that disproportionately affects military veterans. We completed a qualitative study that identified 20 research priorities of Canadian veterans living with chronic noncancer pain. The aim of this study was to establish the generalizability of these priorities.

Materials and Methods

From January to March 2021, we emailed a 45-item survey to a list of Canadian veterans living with chronic noncancer pain that asked about the relative importance of 20 research priorities.

Results

Overall, 313 of 701 Canadian military veterans living with chronic noncancer pain returned a completed survey (45% response rate). All 20 research priorities listed in the survey were endorsed by ≥75% of respondents, and four received ≥95% endorsement: (1) optimizing chronic pain management after release from the military; (2) establishing the effectiveness of self-care; and (3) identifying and (4) treating mental illness among veterans living with chronic pain. One research priority differed significantly by gender; 50% more females than males rated improving chronic pain care while in the military as important (99% vs. 49%, P < .001).

Conclusions

Our survey established research priorities among Canadian veterans living with chronic noncancer pain. These findings should be considered by granting agencies when formulating calls for proposals and by researchers who wish to undertake research that will address the needs of military veterans living with chronic pain.
Mean opacities of a strongly magnetized high-temperature plasma
Authors: Suleimanov Valery F , Mushtukov Alexander A , Ognev Igor , Doroshenko Victor A , Werner Klaus
Published: October 2022

Geometry and dynamical structure of emission regions in accreting pulsars are shaped by the interplay between gravity, radiation, and strong magnetic field, which significantly affects the opacities of a plasma and radiative pressure under such extreme conditions. Quantitative consideration of magnetic plasma opacities is therefore an essential ingredient of any self-consistent modelling of emission region structure of X-ray pulsars (XRPs). We present results of computations of the Rosseland and Planck mean opacities of a strongly magnetized plasma with a simple chemical composition, namely the solar hydrogen/helium mix. We consider all relevant specific opacities of the magnetized plasma including vacuum polarization effect and contribution of electron–positron pairs where the pair number density is computed in the thermodynamic equilibrium approximation. The magnetic Planck mean opacity determines the radiative cooling of an optically thin strongly magnetized plasma. It is by factor of three smaller than non-magnetic Planck opacity at $k_{\rm B}T \lt 0.1\, E_{\rm cyc}$ and increases by a factor of 102–104 at $k_{\rm B}T \gt 0.3\, E_{\rm cyc}$ due to cyclotron thermal processes. We propose a simple approximate expression which has sufficient accuracy for the magnetic Planck opacity description. We provide the Rosseland opacity in a tabular form computed in the temperature range 1–300 keV, magnetic field range 3 × 1010–1015 G, and a broad range of plasma densities. We demonstrate that the scattering on the electron–positron pairs increases the Rosseland opacity drastically at temperatures > 50 keV in the case of mass densities typical for accretion channel in XRPs.
Genetic architecture underlying IgG-RF production is distinct from that of IgM-RF
Authors: Yaku Ai , Ishikawa Yuki , Iwasaki Takeshi , Hiwa Ryosuke , Matsuo Keitaro , Saji Hiroh , Yurugi Kimiko , Miura Yasuo , Furu Moritoshi , Ito Hiromu , Fujii Takao , Maekawa Taira , Hashimoto Motomu , Ohmura Koichiro , Mimori Tsuneyo , Terao Chikashi
Published: October 2022

Objective

HLA-DRB1 alleles, particularly the shared epitope (SE) alleles, are strongly associated with RA. Different genetic structures underlie the production of the various autoantibodies in RA. While extensive genetic analyses have been conducted to generate a detailed profile of ACPA, a representative autoantibody in RA, the genetic architecture underlying subfractions of RF other than IgM-RF, namely IgG-RF, known to be associated with rheumatoid vasculitis, is not well understood.

Methods

We enrolled a total of 743 RA subjects whose detailed autoantibody (IgG-RF, IgM-RF, and ACPA) data were available. We evaluated co-presence and correlations of the levels of these autoantibodies. We analysed associations between the presence or levels of the autoantibodies and HLA-DRB1 alleles for the 743 RA patients and 2008 healthy controls.

Results

We found both IgG-RF(+) and IgG-RF(–) RA subjects showed comparable associations with SE alleles, which was not observed for the other autoantibodies. Furthermore, there was a clear difference in SE allele associations between IgG-RF(+) and (–) subsets: the association with the IgG-RF(+) subsets was solely driven by HLA-DRB1*04:05, the most frequent SE allele in the Japanese population, while not only HLA-DRB1*04:05 but also HLA-DRB1*04:01, less frequent in the Japanese population but the most frequent SE allele in Europeans, were main drivers of the association in the IgG-RF(–) subset. We confirmed that these associations were irrespective of ACPA presence.

Conclusion

We found a unique genetic architecture for IgG-RF(–) RA, which showed a strong association with a SE allele not frequent in the Japanese population but the most frequent SE allele in Europeans. The findings could shed light on uncovered RA pathology.
The association between autoantibodies and risk for venous thromboembolic events among patients with rheumatoid arthritis
Authors: Westerlind Helga , Kastbom Alf , Rönnelid Johan , Hansson Monika , Alfredsson Lars , Mathsson-Alm Linda , Serre Guy , Cornillet Martin , Holmdahl Rikard , Skriner Karl , Bang Holger , Klareskog Lars , Saevarsdottir Saedis , Lundberg Karin , Grönwall Caroline , Askling Johan
Published: October 2022

Objectives

To assess the association between venous thromboembolic (VTE) events and autoantibodies, following patients from RA diagnosis, measuring occurrence, levels and collective load of different autoantibodies against post-translational protein modifications, in particular recognizing citrullination (e.g. citrullinated fibrinogen) and RF by isotype.

Methods

A cohort of 2814 patients with newly diagnosed RA were followed for incident VTE through register linkages. Sera from RA diagnosis were centrally analysed for antibodies to second generation cyclic citrullinated peptides (anti-CCP2), 20 anti-citrullinated protein antibody (ACPA) fine-specificities, antibodies to additional protein modifications (carbamylation and acetylation) and RF by isotype. Association between baseline serology status and future VTE was analysed using Cox regression adjusted for age, sex and calendar period of RA diagnosis, overall and stratified by anti-CCP2 and RF positivity.

Results

During a median 16 years of follow-up, 213 first-ever VTE events were registered (5.0/1000 person-years). IgG anti-CCP2 (present in 65% of cohort) associated with VTE (hazard ratio [HR] = 1.33, 95% CI: 1.00, 1.78), in a dose-response manner. The risk of VTE increased with number of ACPA fine-specificities. IgM RF, but no other RF isotypes, associated with VTE (HR = 1.38, 95% CI: 1.04, 1.82). The associations were independent from smoking and HLA-DRB1 shared epitope alleles. None of the carbamylated or acetylated antibody reactivities associated with VTE.

Conclusion

Anti-CCP2, load of ACPA fine-specificities and IgM RF at RA diagnosis are associated with an increased risk of future VTE in RA. Antibodies to citrullinated fibrinogen did not differ substantially from other ACPA fine-specificities. Autoreactivity to other post-translational modifications was not associated with VTE risk.
Enhancing Nursing Students’ Cultural Competency
Authors: Massarelli Jennifer
Published: October 2022

This project aimed to explore the cultural competence of third-year undergraduate nursing students. A retrospective, quantitative, quasi-experimental design was used to collect data from 15 undergraduate students who took part in a three-week travel abroad community clinical to Thailand during 2019. Students engaged in reflective journaling. Data were collected before and after travel using the 20-item Cultural Intelligence Scale. Post mean scores were higher than presurveys, indicating that students improved on cultural competency overall. All subcategories showed a positive difference, and the results were overall statistically significant.
Exploring cardiac effects after oxytocin 2.5 IU or carbetocin 100 μg
Authors: Bekkenes Maria Egeland , Fagerland Morten Wang , Solberg Ole Geir , Aaberge Lars , Klingenberg Olav , Norseth Jon , Rosseland Leiv Arne
Published: October 2022

BACKGROUND

Oxytocin can stimulate release of myocardial biomarkers troponin I and T, prolong QTc and induce ST-depression.

OBJECTIVE

To explore cardiac changes after either intravenous carbetocin or oxytocin.

STUDY DESIGN

Exploratory phase 4 randomised controlled trial.

SETTING

Obstetrics units of Oslo University Hospital, Norway between September 2015 and May 2018.

PARTICIPANTS

Forty healthy, singleton pregnant women aged 18 to 50 years at gestational age at least 36 weeks with a planned caesarean delivery.

INTERVENTIONS

Participants were randomised to receive either oxytocin 2.5 IU or carbetocin 100 μg immediately after delivery.

MAIN OUTCOME MEASURES

The primary endpoint was the assessment of troponin I within 48 h of study drug administration. Troponin I and T, and creatine kinase myocardial band assessments were measured before spinal anaesthesia (baseline), and again at 4, 10 and 24 h after delivery. QTc, ST-depression and relative increase in heart rate were recorded from start of study drug administration to 10 min after delivery. All adverse events were monitored.

RESULTS

Compared with the carbetocin group, higher troponin I levels were observed in the oxytocin group at 4 h and 10 h after delivery. For both treatment groups, an increase from baseline in troponin I and T was most pronounced at 10 h after delivery, and it had begun to decline by 24 h. QTc increased with time after administration of both study drugs, with a mean maximum increase of 10.4 ms observed at 9 min (P 
< 0.001). No statistical differences were observed in QTc (P = 0.13) or ST-depression (P = 0.11) between the treatment groups.

CONCLUSIONS

Oxytocin 2.5 IU and carbetocin 100 μg caused a similar increase in QTc. The trial was underpowered with regards to ST-depression and the release of myocardial biomarkers and these warrant further investigation. Data from this trial will inform a larger phase 4 trial to determine potential drug differences in troponin release.

TRIAL REGISTRATION

ClinicalTrials.gov Identifier: NCT02528136
Musculoskeletal Health Climate Is a Prognostic Determinant of Sickness Absence Among Female Eldercare Workers
Authors: Ajstrup Merete , Budtz Cecilie Rud , Nielsen Kent Jacob , Andersen Dorte Raaby , Andersen Johan Hviid , Christiansen David Høyrup
Published: October 2022

Objectives

The present study investigated the association between musculoskeletal health climate, that is, the shared perceptions among workers concerning musculoskeletal health, and sickness absence.

Methods

Questionnaire data on two domains of musculoskeletal health climate, perceived management priority (PMP) and pain acceptance at work (PAW), were collected at baseline. Data on sickness absence were extracted at 1-year follow-up. Data were analyzed using negative binomial multivariable regression.

Results

The final study population comprised 390 female eldercare workers. Compared with participants with low PMP scores, participants with high PMP scores had lower risk of sickness absence (incidence rate ratio, 0.6; 95% confidence interval, 0.4–0.9). Participants with high PAW scores had higher risk of sickness absence than participants with low PAW scores (incidence rate ratio, 1.4; 95% confidence interval, 0.9–2.2).

Conclusions

The results showed an association between the musculoskeletal health climate and sickness absence.
Comprehensive exploration of the expression and prognostic value of AQPs in clear cell renal cell carcinoma
Authors: Wang Huanrui , Zhang Weiyu , Ding Zehua , Xu Tao , Zhang Xiaopeng , Xu Kexin
Published: October 2022

Aquaporins (AQPs) are a family of membrane water channels that facilitate the passive transport of water across the plasma membrane of cells in response to osmotic gradients created by the active transport of solutes. Water-selective AQPs are involved in tumor angiogenesis, invasion, metastasis and growth. However, the polytype expression patterns and prognostic values of eleven AQPs in clear cell Renal Cell Cancer (ccRCC) have yet to be filled.

We preliminarily investigated the transcriptional expression, survival data and immune infiltration of AQPs in patients with renal cell cancer via the Oncomine database, Kaplan–Meier Plotter, UALCAN cancer database, and cBioPortal databases.

The ethical approval was waived by the local ethics committee of Peking University People's Hospital for the natural feature of mine into databases.

The mRNA expression of AQP1/2/3/4/5/6/7/11 was significantly decreased in ccRCC patients. Meanwhile, MIP and AQP1/2/4/6/7/8/9/11 are notably related to the clinical stage or pathological grade of ccRCC. Lower levels of AQP1/3/4/5/7/10 expression were related to worse overall survival (OS) in patients diagnosed with ccRCC. The AQP mutation rate was 25% in ccRCC patients, but genetic alterations in AQPs were unlikely to be associated with OS and disease free survival in ccRCC patients. In addition, the expression of AQP1, AQP3, AQP4 and AQP10 was positively correlated with immune cells, and the expression of AQP6, AQP7 and AQP11 was negatively correlated with immune cells. AQP9 had a strong and significantly positive correlation with multiple immune cells.

Abnormal expression of AQPs in ccRCC indicated the prognosis and immunomodulatory state of ccRCC. Further study needs to be performed to explore AQPs as new biomarkers for ccRCC.
The angiotensin receptor and neprilysin inhibitor, LCZ696, in heart failure: A meta-analysis of randomized controlled trials
Authors: Chen Yan , He Qian , Mo Dun-Chang , Chen Long , Lu Jia-Lu , Li Rui-Xing , Huang Jie
Published: October 2022

Background:

LCZ696 is a novel neuroendocrine inhibitor that has been widely used in heart failure (HF). However, its advantage over other neuroendocrine inhibitors, such as angiotensin-converting enzyme inhibitors (ACEis) and angiotensin-receptor blockers (ARBs) has not been fully elucidated. This study aimed to provide the latest evidence regarding the efficacy and safety of LCZ696 as compared to other ACEis and ARBs with regards to the treatment of HF.

Methods:

We systematically searched databases, including PubMed, Embase, and the Cochrane Library, for relevant randomized controlled trials (RCTs). The outcome measures included all-cause mortality, rate of hospitalizations for HF, rate of death from cardiovascular causes, change in N-terminal pro-brain natriuretic peptide (NT-proBNP) levels, and decline of renal function.

Results:

Five RCTs involving 19,078 patients were identified. The meta-analysis indicated that LCZ696 was associated with a significant reduction in all-cause mortality (hazard ratio [HR] = 0.84; 95% confidence interval [CI], 0.76–0.93; P = .0005), rate of hospitalizations for HF (HR = 0.80; 95% CI, 0.73–0.87; P < .00001), reduction in NT-proBNP levels (rate ratio = 0.78; 95% CI, 0.70–0.88; P < .0001), and decline in renal function (odds ratio = 0.77; 95% CI, 0.68–0.88; P < .0001) compared with ACEis and ARBs. However, there was no statistical difference in the rate of death from cardiovascular causes (HR = 0.86; 95% CI, 0.72–1.03; P = .09) between LCZ696 and ACEis and ARBs.

Conclusion:

LCZ696 is superior to ACEis and ARBs in the treatment of HF. Hence, it should be more widely used clinically.
Predictor assessment of complete miscarriage after medical treatment for early pregnancy loss in women with previous cesarean section
Authors: Lu Ye , Su Ruide , Chen Ruixin , Wang Wenrong , An Jian
Published: October 2022

This study aimed to evaluate clinical predictors associated with complete miscarriage after medical treatment for early pregnancy loss (EPL) in women with previous cesarean section.

Patients with retained uterine content after expulsion followed by administration of mifepristone and misoprostol were included if they chose continued medical treatment rather than surgical intervention. Clinical characteristics including maternal age, gravidity, parity, history of previous cesarean section and ultrasound findings regarding average diameter of the gestational sac, uterine position, width, and blood flow signal of the residual uterine content after expulsion of the gestational sac were included in the analysis to determine predictors of complete miscarriage. A recursive partitioning analysis (RPA) was used to divide the patients into probability groups and assess their probability of complete miscarriage.

A total of 89 patients were analyzed. The complete miscarriage rate was 58.43% overall. Multivariable logistic regression analysis showed that the width and blood flow signal of the residual after expulsion were both independent predictors for complete miscarriage (all P < .05). Patients were divided into high-probability (no blood flow signal, width of residual <1 cm), intermediate-probability (no blood flow signal, width of residual ≥1 cm; blood flow signal, width of residual <1 cm), and low-probability (blood flow signal, width of residual ≥ 1 cm) groups by RPA according to these 2 factors. The incidences of complete miscarriage were 88.24%, 67.57%, and 34.29%, respectively, P < .001).

Surgical evacuation may be avoided in patients without ultrasonic blood flow of the uterine residual and width of the residual <1 cm. More active treatment could be recommended for patients with ultrasonic blood flow of the uterine residual and width of the residual ≥ 1 cm. Clinicians and patients should be aware of these differences when proceeding with medical treatment for EPL patients with previous cesarean section.
Role of 68Ga-FAPI PET/CT in Screening Malignancy of Familial Adenomatous Polyposis
Authors: Erol Fenercioğlu Özge , Yarikkaya Enver , Beyhan Ediz , Çermik Tevfik Fikret , Ergül Nurhan
Published: October 2022

A 57-year-old man with familial adenomatous polyposis (FAP) and newly diagnosed colonic adenocarcinoma was referred to 18F-FDG PET/CT for staging and 68Ga-FAPI-04 PET/CT for ongoing trial. 18F-FDG PET/CT showed equal intense 18F-FDG uptake in the tumor and multiple hypermetabolic polypoid lesions in the entire colorectum. 68Ga-FAPI-04 PET/CT showed intense 68Ga-FAPI-04 uptake only at the colonic tumor, without uptake at polypoid lesions.
Trichoderma atroviride hyphal regeneration and conidiation depend on cell-signaling processes regulated by a microRNA-like RNA
Authors: Villalobos-Escobedo José M. , Martínez-Hernández J. Pedro , Pelagio-Flores Ramón , González-De la Rosa Pablo M. , Carreras-Villaseñor Nohemí , Abreu-Goodger Cei , Herrera-Estrella Alfredo H.
Published: October 2022

The ability to respond to injury is essential for the survival of an organism and involves analogous mechanisms in animals and plants. Such mechanisms integrate coordinated genetic and metabolic reprogramming events requiring regulation by small RNAs for adequate healing of the wounded area. We have previously reported that the response to injury of the filamentous fungus Trichoderma atroviride involves molecular mechanisms closely resembling those of plants and animals that lead to the formation of new hyphae (regeneration) and the development of asexual reproduction structures (conidiophores). However, the involvement of microRNAs in this process has not been investigated in fungi. In this work, we explore the participation of microRNA-like RNAs (milRNAs) molecules by sequencing messenger and small RNAs during the injury response of the WT strain and RNAi mutants. We found that Dcr2 appears to play an important role in hyphal regeneration and is required to produce the majority of sRNAs in T. atroviride. We also determined that the three main milRNAs produced via Dcr2 are induced during the damage-triggered developmental process. Importantly, elimination of a single milRNA phenocopied the main defects observed in the dcr2 mutant. Our results demonstrate the essential role of milRNAs in hyphal regeneration and asexual development by post-transcriptionally regulating cellular signalling processes involving phosphorylation events. These observations allow us to conclude that fungi, like plants and animals, in response to damage activate fine-tuning regulatory mechanisms.
Patterns of litigation in France during two decades of recovery of a large carnivore
Authors: Chapron Guillaume , Marfaing Gavin , Bétaille Julien
Published: October 2022

The recovery of large carnivores in Europe’s human dominated landscapes is an unexpected conservation success. In France, where the wolf disappeared in 1937, the species population is now approaching one thousand individuals after the species naturally returned in the country in 1992 from Italy. Large carnivores in Europe are protected by several legal instruments, ranging from international law, to European, national or regional laws (in federal countries). There has been a limited attention allocated to how this legal protection is in practice activated in Member States of the European Union. In particular, there is little research on the role of public interest environmental litigation for large carnivore conservation. We take the example of the wolf (Canis lupus) in France and describe wolf-related litigation in the country during two decades. We compiled a database of case law decisions (i.e. court rulings) relating to administrative litigation about the protection of the wolf and collected a total of 275 court rulings. We found that wolf litigation occurred unsurprisingly more often in administrative courts located in regions where wolves first returned (i.e. South-East of France). Animal welfare or protection associations were the most active and successful plaintiffs. The State administration represented by its Préfets was also a plaintiff in lawsuits against illegal culling decisions made by mayors. The Préfet des Alpes Maritimes and the Minister of the Environment were regular defendants for decisions to cull wolves that were litigated by nature protection associations. Nature protection associations overall had a case winning rate higher than 50%. There were no immediately obvious inter-annual trends in wolf litigation. Our database did not allow us to quantify the total number of wolves that were effectively protected from culling decisions because court rulings made after the execution of administrative decisions did not specify whether the animals were killed or not. Bet it as it may, nature protection associations appear to conduct legally relevant litigation in view of the high success rate they achieve and conservation lawsuits belong to the portfolio of available conservation instruments.
Unveiling the anisotropic fractal magnetic domain structure in bulk crystals of antiskyrmion host (Fe,Ni,Pd)3P by small-angle neutron scattering
Authors: Karube Kosuke , Ukleev Victor , Kagawa Fumitaka , Tokura Yoshinori , Taguchi Yasujiro , White Jonathan S.
Published: October 2022

Intermetallic Pd-doped (Fe,Ni)3P, which crystallizes in a non-centrosymmetric tetragonal structure with S
4 symmetry, has recently been discovered to host magnetic antiskyrmions, antivortex-like topological spin textures. In this material, uniaxial magnetic anisotropy and dipolar interactions play a significant role, giving rise to finely branched magnetic domain patterns near the surface of bulk crystals, as revealed by a previous magnetic force microscopy (MFM) measurement. However, small-angle neutron scattering (SANS) is a more suitable method for characterizing bulk properties and fractal structures on the mesoscopic length scale. In this study, using SANS and MFM, the magnetic domain structure in bulk single crystals of (Fe0.63Ni0.30Pd0.07)3P is quantitatively investigated. The SANS results demonstrate that the magnetic domain structure exhibits anisotropic fractal character on length scales down to the width of the magnetic domain walls. The fractal features are gradually lost in magnetic fields, and different field dependencies are observed at 300 and 2 K due to a temperature-dependent anisotropy. This study quantifies the fractality of the highly anisotropic magnetic domain structures in an antiskyrmion material, and highlights the versatility of SANS for the study of fractal structures in magnetic systems.