bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prediction of a Positive ANA Result for a Rheumatological Diagnosis in an Outpatient Setting
Authors: Chu Chiu Sum , Ho Ling Yin , Mok Chi Chiu 
Published: July 2023

Objective: To study the predictive value of a positive anti-nuclear antibody (ANA) for a rheumatological diagnosis in an outpatient setting. Methods: Individuals who were referred to the rheumatology outpatient clinics because of a positive ANA between July 2014 and June 2015 were retrospectively reviewed. Presenting symptoms in addition to a positive ANA and whether a final rheumatological diagnosis was made were recorded. The positive predictive value of a positive ANA and its titer for a rheumatological diagnosis, with and without accompanying symptoms was evaluated. Results: A total of 230 patients were included (82% women, age 47.7 ± 14.1 years [range 18-84]). Family medicine and the general outpatient clinic were the main sources of referral (32.2%), followed by ophthalmology (13.0%) and otorhinolaryngology (11.7%). A final rheumatological diagnosis was made in 54 (23.5%) patients, with rheumatoid arthritis being the commonest diagnosis (40.7%). In the absence of any associated symptoms, the predictive value of a positive ANA was 0%. The presence of Raynaud’s phenomenon (100%), joint swelling (59.5%), and joint stiffness (48.9%) predicted a better final rheumatological diagnosis along with a positive ANA. ANA titers of 1:80 or less had a low sensitivity for rheumatic diseases. A receiver operating characteristic (ROC) curve analysis showed that an ANA titer of [Formula: see text]1:128 best predicted a rheumatological diagnosis (AUC 0.78 [0.71–0.85]; sensitivity 0.78; specificity 0.64). Conclusions: To improve the prediction for a rheumatological diagnosis, referral for a positive ANA test should be more appropriately done with compatible symptoms.
Matrix-Binding, N-Cadherin–Targeting Chimeric Peptide Inhibits Intimal Thickening but Not Endothelial Repair in Balloon-Injured Carotid Arteries
Authors: Burke-Kleinman Jonah , Rubianto Jonathan , Hou Guangpei , Santerre J. Paul , Bendeck Michelle P. 
Published: July 2023

BACKGROUND:
Treatment of occluded vessels can involve angioplasty, stenting, and bypass grafting, which can be limited by restenosis and thrombosis. Drug-eluting stents attenuate restenosis, but the current drugs used are cytotoxic, causing smooth muscle cell (SMC) and endothelial cell (EC) death that may lead to late thrombosis. N-cadherin is a junctional protein expressed by SMCs, which promotes directional SMC migration contributing to restenosis. We propose that engaging N-cadherin with mimetic peptides can act as a cell type–selective therapeutic strategy to inhibit polarization and directional migration of SMCs without negatively impacting ECs.

METHODS:

We designed a novel N-cadherin–targeting chimeric peptide with a histidine-alanine-valine cadherin-binding motif, combined with a fibronectin-binding motif from
Staphylococcus aureus
. This peptide was tested in SMC and EC culture assays of migration, viability, and apoptosis. Rat carotid arteries were balloon injured and treated with the N-cadherin peptide.

RESULTS:
Treating scratch-wounded SMCs with the N-cadherin–targeting peptide inhibited migration and reduced polarization of wound-edge cells. The peptide colocalized with fibronectin. Importantly, EC junction, permeability, or migration was not impacted by peptide treatment in vitro. We also demonstrated that the chimeric peptide persisted for 24 hours after transient delivery in the balloon-injured rat carotid artery. Treatment with the N-cadherin–targeting chimeric peptide reduced intimal thickening in balloon-injured rat carotid arteries at 1 and 2 weeks after injury. Reendothelialization of injured vessels after 2 weeks was unimpaired by peptide treatment.

CONCLUSIONS:
These studies show that an N-cadherin–binding and fibronectin-binding chimeric peptide is effective in inhibiting SMC migration in vitro and in vivo and limiting neointimal hyperplasia after balloon angioplasty without affecting EC repair. These results establish the potential of an advantageous SMC-selective strategy for antirestenosis therapy.
Long-Term Prevalence of Systolic Dysfunction in MYBPC3 Versus MYH7-Related Hypertrophic Cardiomyopathy
Authors: Beltrami Matteo , Fedele Elisa , Fumagalli Carlo , Mazzarotto Francesco , Girolami Francesca , Ferrantini Cecilia , Coppini Raffaele , Tofani Lorenzo , Bertaccini Bruno , Poggesi Corrado , Olivotto Iacopo 
Published: July 2023

BACKGROUND:
The 2 sarcomere genes most commonly associated with hypertrophic cardiomyopathy (HCM), MYBPC3 (myosin-binding protein C3) and MYH7 (β-myosin heavy chain), are indistinguishable at presentation, and genotype-phenotype correlations have been elusive. Based on molecular and pathophysiological differences, however, it is plausible to hypothesize a different behavior in myocardial performance, impacting lifetime changes in left ventricular (LV) function.

METHODS:
We reviewed the initial and final echocardiograms of 402 consecutive HCM patients with pathogenic or likely pathogenic MYBPC3 (n=251) or MYH7 (n=151) mutations, followed over 9±8 years.

RESULTS:

At presentation, MYBPC3 patients were less frequently obstructive (15% versus 26%;
P
=0.005) and had lower LV ejection fraction compared with MYH7 (66±8% versus 68±8%, respectively;
P
=0.03). Both HCM patients harboring MYBPC3 and MYH7 mutations exhibited a small but significant decline in LV systolic function during follow-up; however, new onset of severe LV systolic dysfunction (LV ejection fraction, <50%) was greater among MYBPC3 patients (15% versus 5% among MYH7;
P
=0.013). Prevalence of grade II/III diastolic dysfunction at final evaluation was comparable between MYBPC3 and MYH7 patients (
P
=0.509). In a Cox multivariable analysis, MYBPC3-positive status (hazard ratio, 2.53 [95% CI, 1.09–5.82];
P
=0.029), age (hazard ratio, 1.03 [95% CI, 1.00–1.06];
P
=0.027), and atrial fibrillation (hazard ratio, 2.39 [95% CI, 1.14–5.05];
P
=0.020) were independent predictors of severe systolic dysfunction. No statistically significant differences occurred with regard to incidence of atrial fibrillation, heart failure, appropriate implanted cardioverter defibrillator shock, or cardiovascular death.

CONCLUSIONS:
MYBPC3-related HCM showed increased long-term prevalence of systolic dysfunction compared with MYH7, in spite of similar outcome. Such observations suggest different pathophysiology of clinical progression in the 2 subsets and may prove relevant for understanding of genotype-phenotype correlations in HCM.
From Focal Homonymy to the Ambiguity of Existence (tashkīk al-wujūd): Avicenna’s Reception and Revision of Aristotle’s Categorial Ontology
Authors: Candy Zachary 
Published: July 2023

Abstract
This paper argues that both Aristotle’s theory of the so-called focal homonymy of “being” and Avicenna’s corresponding theory of the ambiguity of “existence” (tashkīk al-wujūd) are meant to address the same dilemma of categorial ontology, but by recourse to different solutions. Avicenna retains Aristotle’s concerns but rejects his solution of focal homonymy, offering a new theory which more satisfactorily addresses each horn of the dilemma. This reading departs from prior scholarship, which, taking Avicenna to have adopted the focal theory basically intact from his Late Antique predecessors, instead tends to privilege the theory’s (peripheral) theological applications.
Histone acetyltransferase P300 deficiency promotes ferroptosis of vascular smooth muscle cells by activating the HIF-1α/HMOX1 axis
Authors: Shi Juan , Wang Qun-Hui , Wei Xiang , Huo Bo , Ye Jian-Nan , Yi Xin , Feng Xin , Fang Ze-Min , Jiang Ding-Sheng , Ma Ming-Jia 
Published: July 2023

Abstract
Background
E1A-associated 300-kDa protein (P300), an endogenous histone acetyltransferase, contributes to modifications of the chromatin landscape of genes involved in multiple cardiovascular diseases. Ferroptosis of vascular smooth muscle cells (VSMCs) is a novel pathological mechanism of aortic dissection. However, whether P300 regulates VSMC ferroptosis remains unknown.

Methods
Cystine deprivation (CD) and imidazole ketone erastin (IKE) were used to induce VSMC ferroptosis. Two different knockdown plasmids targeting P300 and A-485 (a specific inhibitor of P300) were used to investigate the function of P300 in the ferroptosis of human aortic smooth muscle cells (HASMCs). Cell counting kit-8, lactate dehydrogenase and flow cytometry with propidium iodide staining were performed to assess the cell viability and death under the treatment of CD and IKE. BODIPY-C11 assay, immunofluorescence staining of 4-hydroxynonenal and malondialdehyde assay were conducted to detect the level of lipid peroxidation. Furthermore, co-immunoprecipitation was utilized to explore the interaction between P300 and HIF-1α, HIF-1α and P53.

Results
Compared with normal control, the protein level of P300 was significantly decreased in HASMCs treated with CD and IKE, which was largely nullified by the ferroptosis inhibitor ferrostatin-1 but not by the autophagy inhibitor or apoptosis inhibitor. Knockdown of P300 by short-hairpin RNA or inhibition of P300 activity by A-485 promoted CD- and IKE-induced HASMC ferroptosis, as evidenced by a reduction in cell viability and aggravation of lipid peroxidation of HASMCs. Furthermore, we found that hypoxia-inducible factor-1α (HIF-1α)/heme oxygenase 1 (HMOX1) pathway was responsible for the impacts of P300 on ferroptosis of HASMCs. The results of co-immunoprecipitation demonstrated that P300 and P53 competitively bound HIF-1α to regulate the expression of HMOX1. Under normal conditions, P300 interacted with HIF-1α to inhibit HMOX1 expression, while reduced expression of P300 induced by ferroptosis inducers would favor HIF-1α binding to P53 to trigger HMOX1 overexpression. Furthermore, the aggravated effects of P300 knockdown on HASMC ferroptosis were largely nullified by HIF-1α knockdown or the HIF-1α inhibitor BAY87-2243.

Conclusion
Thus, our results revealed that P300 deficiency or inactivation facilitated CD- and IKE-induced VSMC ferroptosis by activating the HIF-1α/HMOX1 axis, which may contribute to the development of diseases related to VSMC ferroptosis.
Minimal important difference, patient acceptable symptom state and longitudinal validity of oxford elbow score and the quickDASH in patients with tennis elbow
Authors: Karjalainen Teemu , Lähdeoja Tuomas , Salmela Mikko , Ardern Clare L , Juurakko Joona , Järvinen Teppo LN , Taimela Simo ,   FINITE investigators
Published: July 2023

Abstract
Background
The Oxford Elbow Score (OES) and the short version of Disabilities of Arms, Shoulder and Hand (QuickDASH) are common patient-reported outcomes for people with elbow problems. Our primary objective was to define thresholds for the Minimal Important Difference (MID) and Patient-Acceptable Symptom State (PASS) for the OES and QuickDASH. The secondary aim was to compare the longitudinal validity of these outcome measures.

Methods
We recruited 97 patients with clinically-diagnosed tennis elbow for a prospective observational cohort study in a pragmatic clinical setting. Fifty-five participants received no specific intervention, 14 underwent surgery (11 as primary treatment and 4 during follow-up), and 28 received either botulinum toxin injection or platelet rich plasma injection. We collected OES (0 to 100, higher is better) and QuickDASH (0 to 100, higher is worse), and global rating of change (as an external transition anchor question) at six weeks, three months, six months and 12 months. We defined MID and PASS values using three approaches. To assess the longitudinal validity of the measures, we calculated the Spearman’s correlation coefficient between the change in the outcome scores and external transition anchor question, and the Area Under the Curve (AUC) from a receiver operating characteristics (ROC) analysis. To assess signal-to-noise ratio, we calculated standardized response means.

Results
Depending on the method, MID values ranged from 16 to 21 for OES Pain; 10 to 17 for OES Function; 14 to 28 for OES Social-psychological; 14 to 20 for OES Total score, and − 7 to -9 for QuickDASH. Patient-Acceptable Symptom State (PASS) cut offs were 74 to 84 for OES Pain; 88 to 91 for OES Function; 75 to 78 with OES Social-psychological; 80 to 81 with OES Total score and 19 to 23 with Quick-DASH. OES had stronger correlations with the anchor items, and AUC values suggested superior discrimination (between improved and not improved) compared with QuickDASH. OES also had superior signal-to-noise ratio compared with QuickDASH.

Conclusion
The study provides MID and PASS values for OES and QuickDASH. Due to better longitudinal validity, OES may be a better choice for clinical trials.

Trial registration
ClinicalTrials.gov NCT02425982 (first registered April 24, 2015).
The impact of iterative removal of low-information cluster-period cells from a stepped wedge design
Authors: Rezaei-Darzi Ehsan , Grantham Kelsey L. , Forbes Andrew B. , Kasza Jessica 
Published: July 2023

Abstract
Background
Standard stepped wedge trials, where clusters switch from the control to the intervention condition in a staggered manner, can be costly and burdensome. Recent work has shown that the amount of information contributed by each cluster in each period differs, with some cluster-periods contributing a relatively small amount of information. We investigate the patterns of the information content of cluster-period cells upon iterative removal of low-information cells, assuming a model for continuous outcomes with constant cluster-period size, categorical time period effects, and exchangeable and discrete-time decay intracluster correlation structures.

Methods
We sequentially remove pairs of “centrosymmetric” cluster-period cells from an initially complete stepped wedge design which contribute the least amount of information to the estimation of the treatment effect. At each iteration, we update the information content of the remaining cells, determine the pair of cells with the lowest information content, and repeat this process until the treatment effect cannot be estimated.

Results
We demonstrate that as more cells are removed, more information is concentrated in the cells near the time of the treatment switch, and in “hot-spots” in the corners of the design. For the exchangeable correlation structure, removing the cells from these hot-spots leads to a marked reduction in study precision and power, however the impact of this is lessened for the discrete-time decay structure.

Conclusions
Removing cluster-period cells distant from the time of the treatment switch may not lead to large reductions in precision or power, implying that certain incomplete designs may be almost as powerful as complete designs.
Revascularization of acute stent thrombosis caused by diarrhea after carotid artery stenting in an intermediate clopidogrel metabolizer
Authors: Wang Huaishun , Xu Longdong , Qin Yan , Xiao Guodong 
Published: July 2023

AbstractCarotid artery stenting (CAS) is an alternative treatment to carotid endarterectomy for carotid artery stenosis. Acute stent thrombosis (ACST) is an extremely rare complication but can have devastating consequences. Although many cases have been reported, the best treatment is still uncertain. In this study, we report the treatment of ACST caused by diarrhea in an intermediate clopidogrel metabolizer. We also review the literature and discuss appropriate treatment strategies for this rare event.
Determinants of postpartum uterine atony in urban South Ethiopia: a community-based unmatched nested case–control study
Authors: Jena Belayneh Hamdela , Biks Gashaw Andargie , Gete Yigzaw Kebede , Gelaye Kassahun Alemu 
Published: July 2023

Abstract
Background
Uterine atony is the most common cause of postpartum hemorrhage, which is the leading preventable cause of maternal morbidity and mortality. Despite several interventions uterine atony-related postpartum hemorrhage remains a global challenge. Identifying risk factors of uterine atony helps to reduce the risk of postpartum hemorrhage and subsequent maternal death. However, evidence about risk factors of uterine atony is limited in the study areas to suggest interventions. This study aimed to assess determinants of postpartum uterine atony in urban South Ethiopia.

Methods
A community-based unmatched nested case–control study was conducted from a cohort of 2548 pregnant women who were followed-up until delivery. All women with postpartum uterine atony (n = 93) were taken as cases. Women who were randomly selected from those without postpartum uterine atony (n = 372) were taken as controls. Using a case to control ratio of 1:4, the total sample size was 465. An unconditional logistic regression analysis was done using R version 4.2.2 software. In the binary unconditional logistic regression model variables that have shown association at p < 0.20 were recruited for multivariable model adjustment. In the multivariable unconditional logistic regression model, statistically significant association was declared using 95% CI and p < 0.05. Adjusted odds ratio (AOR) used to measure the strength of association. Attributable fraction (AF) and population attributable fraction (PAF) were used to interpret the public health impacts of the determinants of uterine atony.

Results
In this study, short inter-pregnancy interval < 24 months (AOR = 2.13, 95% CI: 1.26, 3.61), prolonged labor (AOR = 2.35, 95% CI: 1.15, 4.83), and multiple birth (AOR = 3.46, 95% CI: 1.25, 9.56) were determinants of postpartum uterine atony. The findings suggest that 38%, 14%, and 6% of uterine atony in the study population was attributed to short inter-pregnancy interval, prolonged labor, and multiple birth, respectively, which could be prevented if those factors did not exist in the study population.

Conclusions
Postpartum uterine atony was related to mostly modifiable conditions that could be improved by increasing the utilization of maternal health services such as modern contraceptive methods, antenatal care and skilled birth attendance in the community.
Apigenin inhibits angiogenesis in retinal microvascular endothelial cells through regulating of the miR-140-5p/HDAC3-mediated PTEN/PI3K/AKT pathway
Authors: Fu Chaojun , Peng Jun , Ling Yanjun , Zhao Hongqing , Zhao Yongwang , Zhang Xiuli , Ai Min , Peng Qinghua , Qin Yuhui 
Published: July 2023

Abstract
Background
Diabetic retinopathy (DR) is a common cause of visual impairment. Apigenin has been shown to have antiangiogenic effects in various diseases. Our study aimed to investigate the role of apigenin in DR and elucidate the underlying mechanism.

Methods
Human retinal microvascular endothelial cells (HRMECs) were exposed to high glucose (HG) to establish a DR model. HRMECs were treated with apigenin. Then we knocked down or overexpressed miR-140-5p and HDAC3, and added PI3K/AKT inhibitor LY294002. The expression levels of miR-140-5p, HDAC3, and PTEN were measured using qRT-PCR. Western blot analysis was performed to assess the expression of HDAC3, PTEN, and PI3K/AKT pathway-related proteins. Finally, cell proliferation and migration were evaluated using MTT, wound-healing assay, and transwell assay, while angiogenesis was examined using the tube formation assay.

Results
HG treatment resulted in reduced miR-140-5p expression and overexpression of miR-140-5p suppressed proliferation, migration, and angiogenesis of the HG-induced HRMECs. Apigenin treatment significantly restored the decreased level of miR-140-5p caused by HG treatment and inhibited proliferation, migration, and angiogenesis of the HG-induced HRMECs by upregulating miR-140-5p. Moreover, miR-140-5p targeted HDAC3, and overexpression of miR-140-5p reversed the HG-inducted upregulation of HDAC3 expression. HDAC3 was found to bind to the promoter region of PTEN, inhibiting its expression. Knockdown of HDAC3 suppressed the PI3K/AKT pathway by elevating PTEN expression. Furthermore, apigenin inhibited angiogenesis in DR cell models through the regulating of the miR-140-5p/HDAC3-mediated PTEN/PI3K/AKT pathway.

Conclusions
Apigenin effectively suppressed angiogenesis in HG-induced HRMECs by modulating the miR-140-5p/HDAC3-mediated PTEN/PI3K/AKT pathway. Our study may contribute to the development of novel therapeutic approaches and identification of potential targets for the treatment of DR.
Longitudinal social contact data analysis: insights from 2 years of data collection in Belgium during the COVID-19 pandemic
Authors: Loedy Neilshan , Coletti Pietro , Wambua James , Hermans Lisa , Willem Lander , Jarvis Christopher I. , Wong Kerry L. M. , Edmunds W. John , Robert Alexis , Leclerc Quentin J. , Gimma Amy , Molenberghs Geert , Beutels Philippe , Faes Christel , Hens Niel 
Published: July 2023

AbstractBackgroundDuring the COVID-19 pandemic, the CoMix study, a longitudinal behavioral survey, was designed to monitor social contacts and public awareness in multiple countries, including Belgium. As a longitudinal survey, it is vulnerable to participants’ “survey fatigue”, which may impact inferences.MethodsA negative binomial generalized additive model for location, scale, and shape (NBI GAMLSS) was adopted to estimate the number of contacts reported between age groups and to deal with under-reporting due to fatigue within the study. The dropout process was analyzed with first-order auto-regressive logistic regression to identify factors that influence dropout. Using the so-called next generation principle, we calculated the effect of under-reporting due to fatigue on estimating the reproduction number.ResultsFewer contacts were reported as people participated longer in the survey, which suggests under-reporting due to survey fatigue. Participant dropout is significantly affected by household size and age categories, but not significantly affected by the number of contacts reported in any of the two latest waves. This indicates covariate-dependent missing completely at random (MCAR) in the dropout pattern, when missing at random (MAR) is the alternative. However, we cannot rule out more complex mechanisms such as missing not at random (MNAR). Moreover, under-reporting due to fatigue is found to be consistent over time and implies a 15-30% reduction in both the number of contacts and the reproduction number ($$R_0$$R0) ratio between correcting and not correcting for under-reporting. Lastly, we found that correcting for fatigue did not change the pattern of relative incidence between age groups also when considering age-specific heterogeneity in susceptibility and infectivity.ConclusionsCoMix data highlights the variability of contact patterns across age groups and time, revealing the mechanisms governing the spread/transmission of COVID-19/airborne diseases in the population. Although such longitudinal contact surveys are prone to the under-reporting due to participant fatigue and drop-out, we showed that these factors can be identified and corrected using NBI GAMLSS. This information can be used to improve the design of similar, future surveys.