bluuebunny/crossref_metadata_2025 huggingface dataset:
Stakeholder consultation to facilitate implementation of interventions for prevention and promotion in mental health in Europe: introducing the design of the ICare Stakeholder Survey
Authors: Nitsch Martina , Waldherr Karin , Zeiler Michael , Klesges Lisa , Jacobi Corinna
Published: March 2021

Background

Online interventions to prevent mental health problems have proven to be effective. However, knowledge about their implementation in real-world practice as well as for dissemination to the target groups in different settings is scarce. The goal of the ‘ICare’ network is to establish a comprehensive model of eMental-health service delivery in and across different European countries. Since implementation and dissemination are influenced by many contextual factors, in the first phase of ICare a stakeholder survey was conducted. The survey aim was to explore stakeholders’ experiences, needs and attitudes regarding Internet-based prevention of mental health problems and hindering and fostering factors for implementation and dissemination. This article is part of a supplement and describes the design of the stakeholder survey. Survey results are published in separate articles in the same supplement.

Methods

Based on a literature review and the individual characteristics of the ICare interventions, stakeholder groups were identified in different settings across six European countries. The RE-AIM framework guided the development of the research questions and survey instruments. A concurrent mixed methods design was applied comprising focus groups with the intended target groups of ICare interventions, an online questionnaire with potential facilitators/delivery staff and semi-structured interviews with policy makers.

Conclusion

The challenge was to develop a design that allowed flexibility but at the same did not jeopardize the validity of the study. Implications drawn from this survey are not restricted to specific preventive interventions but will provide general information on how online mental illness prevention can be best implemented in various settings.
Support Exchanges Among Very Old Parents and Their Children: Findings From the Boston Aging Together Study
Authors: Boerner Kathrin , Kim Kyungmin , Kim Yijung K , Jopp Daniela S
Published: March 2021

Background and Objectives

Very old parents and their “old” children are a growing group in industrialized countries worldwide. Care needs of very old parents can be substantial, while children may also face their own age-related issues. Continued mutual support represents an important pathway to addressing emerging care needs. This study aimed to identify patterns of support exchanges occurring in very old parent–child dyads and to ascertain associated individual and relationship factors.

Research Design and Methods

Participants were 114 very old parents (aged ≥90) and their children (aged ≥65) from the Boston Aging Together Study. Data were collected using comprehensive, semistructured in-person interviews with both dyad members, including standardized assessments of support exchanges, relationship quality, health, and perceptions of family norms. Actor–Partner Interdependence Models were used to predict upward and downward support reported by children and parents.

Results

Both dyad members not only reported substantial upward support (child to parent) in all domains but also notable amounts of downward (parent to child) in the domains of emotional support, listening, and socializing. Findings showed significant associations of parent functional impairment, parent and child relationship quality, and child perceptions of family obligation with upward support and of relationship quality with downward support.

Discussion and Implications

Continued support exchanges among very old parents and their children indicated that intergenerational theories still hold up in very late-life relationships. Health care professionals should be aware that attention to relationship quality and family norms might be vital to ensure that support needs are met.
False lumen enhancement characteristics on computed tomography angiography predict risk of aneurysm formation in acute type B aortic dissection
Authors: Roseland Molly E , Ahmed Yunus , van Herwaarden Joost A , Moll Frans L , Yang Bo , Patel Himanshu J , Burris Nicholas S
Published: March 2021

OBJECTIVES

Differential luminal enhancement [between true lumen (TL) and false lumen (FL)] results from differential flow patterns, most likely due to outflow restriction in the FL. We aimed to assess the impact of differential luminal enhancement at baseline computed tomography angiography on the risk of adverse events in patients with acute type B aortic dissection (TBAD).

METHODS

Baseline computed tomography angiographies of patients with acute TBAD between 2007 and 2016 (n = 48) were analysed using three-dimensional software at multiple sites along the descending thoraco-abdominal aorta. At each location, we measured contrast density in TL and FL [Houndsfield unit (HU)], maximal diameter (cm) and circumferential FL extent (°). Outcome data were collected via retrospective chart review. Multivariable logistic regression models were employed to determine the independent risk of TL–FL differential luminal enhancement on aneurysm formation (maximal diameter ≥55 mm) and medical treatment failure.

RESULTS

Patients were predominately male (75%) and 52.8±12.9 years at diagnosis. The mean follow-up was 5.9±2.6 years, and 42% (n = 20/48) patients were diagnosed with thoraco-abdominal aortic aneurysm. The baseline absolute difference between FL and TL contrast density measured at 2 cm distal to primary entry tear (TL–FLabs-Tear) was significantly higher among patients who developed aneurysm (26 HU, IQR: 15–53 vs 13 HU, IQR: 4–24, P = 0.001). Aneurysm development during follow-up was predicted by TL–FLabs-Tear (odds ratio 1.07, P = 0.012) and baseline maximal aortic diameter (odds ratio 1.90, P < 0.001). High (≥18 HU) differential luminal enhancement was associated with lower rates of aneurysm-free survival and higher rates of medical treatment failure.

CONCLUSIONS

Differential luminal enhancement may be a novel predictor of aneurysm formation among patients with acute TBAD.
Three-year study of pre-existing drug resistance substitutions and efficacy of bictegravir/emtricitabine/tenofovir alafenamide in HIV-1 treatment-naive participants
Authors: Acosta Rima K , Chen Grace Q , Chang Silvia , Martin Ross , Wang Xinxin , Huang Hailin , Brainard Diana , Collins Sean E , Martin Hal , White Kirsten L
Published: March 2021

Objectives

Two Phase 3, randomized, double-blind, active-controlled studies of initial HIV-1 treatment demonstrated that bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) was non-inferior to dolutegravir/abacavir/lamivudine (DTG/ABC/3TC; Study 1489) or to DTG+F/TAF (Study 1490) through 144 weeks. In both studies, there was no emergent resistance to study drugs. Here, the 3 year resistance analysis and impact of baseline resistance substitutions on treatment response are described.

Methods

Population sequencing of HIV-1 protease and reverse transcriptase (RT) was performed at screening. Retrospective baseline next generation sequencing of protease, RT and integrase (IN) was analysed at a ≥ 15% cutoff. Resistance analyses were performed on participants with confirmed viral rebound of HIV-1 RNA ≥200 copies/mL through Week 144 or last visit who did not resuppress to <50 copies/mL while on study drug.

Results

Transmitted primary drug resistance substitutions were present in the following proportions of participants: integrase strand transfer inhibitor (INSTI) resistance (-R) in 1.3% (17/1270) of participants; NRTI-R in 2.7% (35/1274); NNRTI-R in 14.1% (179/1274); and PI-R in 3.5% (44/1274). These pre-existing resistance substitutions not associated with study drug did not affect treatment outcomes. One participant in the B/F/TAF group had pre-existing bictegravir and dolutegravir resistance substitutions (Q148H+G140S in integrase) at baseline and suppressed and maintained HIV-1 RNA <50 copies/mL through Week 144. In total, 21 participants qualified for resistance testing [1.3% (8/634) B/F/TAF; 1.9% (6/315) DTG/ABC/3TC; 2.2% (7/325) DTG+F/TAF]; none had emergent resistance to study drugs.

Conclusions

Treatment with B/F/TAF, DTG/ABC/3TC, or DTG+F/TAF achieved high, durable rates of virological suppression in HIV-1 treatment-naive participants. The presence of pre-existing resistance substitutions did not affect treatment outcomes, and there was no treatment-emergent resistance.
Successful repair of spontaneous indirect bilateral carotid-cavernous fistula with coil embolization
Authors: Gasparian Suzie A , Chalam K V
Published: March 2021

Bilateral carotid-cavernous fistula (CCF) is a rare disease process, which portends poor visual outcome with delayed diagnosis and treatment. An 82-year-old woman presented with sudden onset of proptosis and decreased vision. A complete ophthalmologic examination along with magnetic resonance (MR) imaging of the brain and orbits, and MR angiography and venography of the brain confirmed the diagnosis of bilateral CCF. Diagnostic cerebral angiogram with concurrent coil embolization of the right cavernous sinus via left superior ophthalmic vein approach was performed. Bilateral indirect CCFs (type D CCF on the right and a type B CCF on the left) regressed completely after unilateral coil embolization. Visual acuity and limitation in extraocular movements significantly improved with complete resolution. In summary, we describe successful management of bilateral concurrent CCF with image-guided embolization and immediate recovery of vision and resolution of ophthalmological symptoms including proptosis and diplopia.
Induction of S-nitrosoglutathione reductase protects root growth from ammonium toxicity by regulating potassium homeostasis in Arabidopsis and rice
Authors: Zhang Lin , Song Haiyan , Li Baohai , Wang Meng , Di Dongwei , Lin Xianyong , Kronzucker Herbert J , Shi Weiming , Li Guangjie
Published: March 2021

Ammonium (NH4+) is toxic to root growth in most plants already at moderate levels of supply, but mechanisms of root growth tolerance to NH4+ remain poorly understood. Here, we report that high levels of NH4+ induce nitric oxide (NO) accumulation, while inhibiting potassium (K+) acquisition via SNO1 (sensitive to nitric oxide 1)/SOS4 (salt overly sensitive 4), leading to the arrest of primary root growth. High levels of NH4+ also stimulated the accumulation of GSNOR (S-nitrosoglutathione reductase) in roots. GSNOR overexpression improved root tolerance to NH4+. Loss of GSNOR further induced NO accumulation, increased SNO1/SOS4 activity, and reduced K+ levels in root tissue, enhancing root growth sensitivity to NH4+. Moreover, the GSNOR-like gene, OsGSNOR, is also required for NH4+ tolerance in rice. Immunoblotting showed that the NH4+-induced GSNOR protein accumulation was abolished in the VTC1- (vitamin C1) defective mutant vtc1-1, which is hypersensititive to NH4+ toxicity. GSNOR overexpression enhanced vtc1-1 root tolerance to NH4+. Our findings suggest that induction of GSNOR increases NH4+ tolerance in Arabidopsis roots by counteracting NO-mediated suppression of tissue K+, which depends on VTC1 function.
Digital humanities, knowledge complexity, and the five ‘aporias’ of digital research
Authors: Edmond Jennifer , Lehmann Jörg
Published: March 2021

This article introduces a frame of reference for understanding the fundamental challenges that inform digital humanities as an interdisciplinary research area between arts, humanities, information, and computer science. Its conclusions are based upon the evidence base developed within an EU-funded collaboration known as Knowledge Complexity, or KPLEX for short (www.kplex-project.eu), in particular via the project’s thirty-eight linked interviews about big data research. When viewed from the perspective of the digital humanities, five distinct points of ‘aporia’ with a significant impact on digital humanities (DH) appear in this corpus, places where the interviewees explicitly or tacitly expose gulfs between the epistemic cultures that contribute to DH and that create tensions between these disciplines, even as they seek to collaborate. This article will explore these areas of apparent irreconcilability, and conclude with a series of reflections on how digital humanities researchers might build upon their unique competency profile to negotiate within these critical conversations, in particular in the framework of the emerging subfield of critical digital humanities.
A data-driven approach to studying changing vocabularies in historical newspaper collections
Authors: Hengchen Simon , Ros Ruben , Marjanen Jani , Tolonen Mikko
Published: March 2021

Nation and nationhood are among the most frequently studied concepts in the field of intellectual history. At the same time, the word ‘nation’ and its historical usage are very vague. The aim in this article was to develop a data-driven method using dependency parsing and neural word embeddings to clarify some of the vagueness in the evolution of this concept. To this end, we propose the following two-step method. First, using linguistic processing, we create a large set of words pertaining to the topic of nation. Second, we train diachronic word embeddings and use them to quantify the strength of the semantic similarity between these words and thereby create meaningful clusters, which are then aligned diachronically. To illustrate the robustness of the study across languages, time spans, as well as large datasets, we apply it to the entirety of five historical newspaper archives in Dutch, Swedish, Finnish, and English. To our knowledge, thus far there have been no large-scale comparative studies of this kind that purport to grasp long-term developments in as many as four different languages in a data-driven way. A particular strength of the method we describe in this article is that, by design, it is not limited to the study of nationhood, but rather expands beyond it to other research questions and is reusable in different contexts.
Global RNA profiles show target selectivity and physiological effects of peptide-delivered antisense antibiotics
Authors: Popella Linda , Jung Jakob , Popova Kristina , Ðurica-Mitić Svetlana , Barquist Lars , Vogel Jörg
Published: March 2021

Antisense peptide nucleic acids (PNAs) inhibiting mRNAs of essential genes provide a straight-forward way to repurpose our knowledge of bacterial regulatory RNAs for development of programmable species-specific antibiotics. While there is ample proof of PNA efficacy, their target selectivity and impact on bacterial physiology are poorly understood. Moreover, while antibacterial PNAs are typically designed to block mRNA translation, effects on target mRNA levels are not well-investigated. Here, we pioneer the use of global RNA-seq analysis to decipher PNA activity in a transcriptome-wide manner. We find that PNA-based antisense oligomer conjugates robustly decrease mRNA levels of the widely-used target gene, acpP, in Salmonella enterica, with limited off-target effects. Systematic analysis of several different PNA-carrier peptides attached not only shows different bactericidal efficiency, but also activation of stress pathways. In particular, KFF-, RXR- and Tat-PNA conjugates especially induce the PhoP/Q response, whereas the latter two additionally trigger several distinct pathways. We show that constitutive activation of the PhoP/Q response can lead to Tat-PNA resistance, illustrating the utility of RNA-seq for understanding PNA antibacterial activity. In sum, our study establishes an experimental framework for the design and assessment of PNA antimicrobials in the long-term quest to use these for precision editing of microbiota.
Habitual Path Dependence of Interorganizational Relationships—A Response to Sydow
Authors: Jensen Laura S , Sedgwick Donna
Published: March 2021

In “Path Dependence and the Roots of Interorganizational Relationship Challenges,” recently published by PPMG, we suggested the utility of path dependency theory in unpacking the developmental dynamics that may feed into contemporary problems of management and governance. Professor Jörg Sydow was moved to submit commentary on our article; we respond to his thoughtful comments in this essay.
Idiosyncratic Risk in Housing Markets
Authors: Giacoletti Marco
Published: March 2021

This paper studies the idiosyncratic risk component of individual house capital gains using data on resales and intermediate capital investments. The idiosyncratic component is large; its dynamics do not follow a random walk; and its magnitude is associated with proxies of information quality and market liquidity at the level of individual properties. Accounting for idiosyncratic risk substantially changes the assessment of the risk-return trade-off for housing: it reduces Sharpe ratios and makes them holding period dependent. I use a simple quantitative portfolio model to show that homeowners may be willing to make significant payments to insure against idiosyncratic housing risk.
TRIM33 gene somatic mutations identified by next generation sequencing in neoplasms of patients with anti-TIF1γ positive cancer-associated dermatomyositis
Authors: Cordel Nadège , Derambure Céline , Coutant Sophie , Mariette Xavier , Jullien Denis , Debarbieux Sébastien , Chosidow Olivier , Meyer Alain , Bessis Didier , Joly Pascal , Mathian Alexis , Levesque Hervé , Sabourin Jean-Christophe , Tournier Isabelle , Boyer Olivier ,   the OncoMyositis Study group, Amoura Zahir , Aouizerate Jessie , Benveniste Olivier , Brocheriou Isabelle , Dechelotte Benoit , Graveleau Julie , Guerzider Pascale , Isaac Sylvie , Kanitakis Jean , Lannes Béatrice , Lazure Thierry , Rigau Valérie , Sibilia Jean
Published: March 2021

Objective

To deep sequence the TRIM33 gene in tumours from patients with cancer-associated anti-TIF1γ autoantibody-positive dermatomyositis (DM) as TRIM33 somatic mutations in tumours may trigger this auto-immune disease.

Methods

Next generation sequencing of tumour DNA samples from patients with cancer-associated anti-TIF1γ autoantibody-positive DM. Fourteen tumours from 13 anti-TIF1γ autoantibody-positive DM individuals were sequenced along with two control tumours from non-DM individuals.

Results

Fourteen probable somatic variants from four tumours were identified in the TRIM33 gene.

Conclusion

These results are in accordance with the previous report of Pinal-Fernandez et al. and support the hypothesis of a role of TRIM33 gene mutations in the pathophysiology of anti-TIF1γ autoantibody-positive DM.
Comparative efficacy of low-dose versus regular-dose colchicine to prevent flares in gout patients initiated on urate-lowering therapies
Authors: Ahn Soo Min , Oh Ji Seon , Hong Seokchan , Lee Chang-Keun , Yoo Bin , Kim Yong-Gil
Published: March 2021

Objective

The objective of this study was to compare the prophylactic effect of regular-dose (RD, 1.2 mg/day) vs low-dose (LD, 0.6 mg/day) colchicine on gout flare when initiating urate-lowering therapy.

Methods

In this retrospective cohort study, we included gout patients who were initiated on either allopurinol or febuxostat, in combination with colchicine therapy and followed them up for 3 months. We analysed the rates of gout flare and adverse events according to the dose of colchicine. We performed the inverse probability of treatment weighting (IPTW) and weighted logistic regression analysis to assess the treatment effect. Analysis of gout flares and adverse events was performed on an intention-to-treat (ITT) and per-protocol (PP) basis.

Results

Of the total of 419 patients with gout, 177 patients (42.2%) received LD colchicine, whereas 242 patients (57.8%) received RD colchicine. Lower BMI and estimated glomerular filtration rate, and higher incidence of cardiovascular disease were seen in the LD group than in the RD group. In IPTW-adjusted analysis, events of gout flare were not significantly different between the LD and RD groups [ITT: 14.3% vs 11.3%; odds ratio (OR): 1.309, 95% CI: 0.668, 2.566, P = 0.432; PP: 15.3% vs 10.0%; OR: 1.623, 95% CI: 0.765, 3.443, P = 0.207]. However, LD colchicine was associated with a lower rate of adverse events than RD colchicine [ITT: 8.2% vs 17.9%; OR: 0.410, 95% CI: 0.217, 0.777; P < 0.05; PP: 8.4% vs 17.2%; OR: 0.442, 95% CI: 0.223, 0.878; P < 0.05].

Conclusion

Our data suggest that LD colchicine can adequately prevent gout flare with fewer adverse events compared with RD colchicine.
Micro-dosing Intravenous Buprenorphine to Rapidly Transition From Full Opioid Agonists
Authors: Thakrar Ashish P. , Jablonski Lindsay , Ratner Jessica , Rastegar Darius A.
Published: March 2021

For patients with opioid use disorder transitioning from methadone or requiring opioid analgesia, initiating buprenorphine for opioid use disorder can be difficult because of the risk of precipitated withdrawal. Low-dose initiation, also known as micro-dosing, is an alternative to standard initiation. Prior studies relied on nonstandard dosing of tablets or films, patches, or buccal formulations, all of which are unavailable in many hospitals. We report a novel approach to micro-dosing using intravenous buprenorphine. Two patients, one on methadone maintenance and another requiring postoperative opioid analgesia, were transitioned to buprenorphine with concurrent full-agonist opioids and without precipitated withdrawal.
Substance Use and Utilization of Prenatal and Postpartum Care
Authors: Nidey Nichole , Kair Laura R. , Wilder Christine , Froehlich Tanya E. , Weber Stephanie , Folger Alonzo , Marcotte Michael , Tabb Karen , Bowers Katherine
Published: March 2021

Objectives:

Prenatal and postpartum care for women with substance use is important due to increased risk of poor health outcomes. The influence of substance use on perinatal care utilization is not well characterized, especially postpartum care. The objective of this study was to examine the effect of substance use during pregnancy on prenatal and postpartum care utilization in a nationally representative sample and to identify maternal characteristics associated with inadequate prenatal and postpartum care among women with substance use.

Methods:

Pregnancy Risk Assessment Monitoring System data (2016–2018) from 8 states were used for this study. Logistic regression models adjusted for complex survey weights and confounder variables were used to estimate the odds of not receiving adequate prenatal care and postpartum care. Weighted Rao-Scott chi-square tests were used to examine maternal characteristics associated with care utilization among women who reported substance use during pregnancy.

Results:

The study included 15,131 women, with 5.3% who reported illicit substance use during pregnancy. In multivariable models, substance use was associated with an increase in the odds of not receiving adequate prenatal care (OR 1.69, CI 1.32, 2.17) and not receiving postpartum care (OR: 1.47, CI 1.10, 1.95). Among women who reported substance use, depression and smoking status were associated with not receiving adequate prenatal or postpartum care.

Conclusions:

Substance use during pregnancy is independently associated with disparities in prenatal and postpartum care access. Future studies are needed to identify how barriers lead to care inequalities and importantly, to identify strategies to improve care utilization.
Reflex Decay Test Can Reveal Ear Involvement in Fabry Disease
Authors: Kiykim Ertugrul , Kaya Melda , Dincer Mevlut Tamer , Bakir Alev , Alagoz Selma , Aktuglu Zeybek Ayse , Gulcicek Sibel , Seyahi Nurhan , Trabulus Sinan , Atas Ahmet
Published: March 2021

Objectives:

Fabry disease (FD) is an X-linked lysosomal storage disorder that causes multisystem involvement, including ear disease. In this study, we aimed to investigate the nature of auditory issues in FD using a wide spectrum of audiological tests.

Design:

This cross-sectional study was conducted between June 2017 and December 2018. We collected the clinical and laboratory data of 40 eligible FD patients, 45 healthy subjects, and 26 diabetic controls. All patients and controls completed audiologic evaluations that included tympanometry, acoustic reflex threshold test, reflex decay test, pure-tone audiometry, speech audiometry, transient otoacoustic emissions (TEOAEs), high-frequency audiometry, and distortion product otoacoustic emission (DPOAE).

Results:

In our study population, hearing was reduced at higher frequencies starting at 4 kHz in both the FD and diabetic groups. Regarding the acoustic reflex threshold test, FD and diabetic patients had similar results. In all frequencies, positive decay was significantly more frequent in FD patients when compared with the diabetic patients and healthy controls (p < 0.001 for each ear). The FD patients and healthy controls had similar results for DPOAE testing.

Conclusions:

We showed that FD patients had a higher rate of reflex decay, indicating retrocochlear involvement. Thus, further investigation of factors associated with retrocochlear involvement could be investigated, such as ABR and speech in noise tests.
Clinical Implications and Debates on the International Study of Comparative Health Effectiveness with Medical and Invasive Approaches Trial
Authors: Saito Yuichi , Nishi Takeshi , Saito Kan , Kitahara Hideki , Kawase Yoshiaki , Matsuo Hitoshi , Kobayashi Yoshio
Published: March 2021

The International Study of Comparative Health Effectiveness with Medical and Invasive Approaches (ISCHEMIA) was eagerly awaited study in the field of ischemic heart disease. Following the presentation and publication of ISCHEMIA, multiple opinions and viewpoints get complicated. The ongoing debates have been including the relevance of coronary revascularization, noninvasive diagnostic methods, and invasive ischemic testing in patients with stable ischemic heart disease (SIHD). Prior to ISCHEMIA, observational studies indicated the potential of coronary revascularization for improving clinical outcomes, while the randomized Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation (COURAGE) trial did not support the plausible concept. Although the Fractional Flow Reserve Versus Angiography for Multivessel Evaluation (FAME) 2 trial implied the superiority of percutaneous coronary intervention over medical therapy alone, the clinical relevance of coronary revascularization to improve outcomes and quality of life has been questioned. As a consequence, the ISCHEMIA trial did not demonstrate clear benefits in reducing clinical events but showed antianginal effects of revascularization. This landmark trial also suggested the difficulties of noninvasive ischemia testing rather than computed tomography angiography. Despite the complex results, the ISCHEMIA trial may simplify the clinical indications of coronary revascularization in patients with SIHD. Future publications from the ISCHEMIA trial and debates on the results will sharpen our thinking and understanding.
Circular RNA circ_0010729 Knockdown Attenuates Oxygen–Glucose Deprivation-Induced Human Cardiac Myocytes Injury by miR-338-3p/CALM2 Axis
Authors: Ma Bocong , Zhao Ming , Guo Zhihao
Published: March 2021

Circular RNAs have pivotal roles in cardiovascular disease. The injury of cardiac myocytes is associated with occurrence of cardiovascular disease. Circular RNA hsa_circ_0010729 (circ_0010729) is associated with cardiac myocytes injury. However, the mechanism of circ_0010729 in cardiac myocytes injury remains largely unclear. In our study, cardiac myocytes were treated by oxygen–glucose deprivation (OGD). The abundances of circ_0010729, microRNA-338-3p (miR-338-3p), and calmodulin 2 (CALM2) were detected by quantitative reverse transcription polymerase chain reaction or Western blot. OGD-induced damage in AC16 cells was assessed by cell viability, apoptosis, and autophagy using Cell Counting Kit-8, flow cytometry, and Western blot analyses. The target relationship of miR-338-3p and circ_0010729 or CALM2 was explored by starBase and dual-luciferase reporter analysis. Our results showed that the circ_0010729 level was enhanced in OGD-treated AC16 cells and murine primary cardiac myocytes. circ_0010729 silence weakened OGD-induced viability inhibition and promotion of apoptosis and autophagy in AC16 cells and murine primary cardiac myocytes. miR-338-3p was sponged by circ_0010729 and miR-338-3p knockdown alleviated the effect of circ_0010729 silence on OGD-induced damage. miR-338-3p directly targeted CALM2 to inhibit OGD-induced damage in AC16 cells. circ_0010729 could regulate CALM2 expression by sponging miR-338-3p. Collectively, circ_0010729 interference mitigated OGD-induced damage in cardiac myocytes through increasing cell viability and inhibiting apoptosis and autophagy by regulating miR-338-3p/CALM2 axis. This study indicated circ_0010729 might act as a target for treatment of cardiovascular disease.
Chrysin Ameliorates Sepsis-Induced Cardiac Dysfunction Through Upregulating Nfr2/Heme Oxygenase 1 Pathway
Authors: Xingyue Li , Shuang Li , Qiang Wang , Jinjuan Fu , Yongjian Yang
Published: March 2021

The incidence of myocardial dysfunction caused by sepsis is high, and the mortality of patients with sepsis can be significantly increased. During sepsis, oxidative stress and inflammation can lead to severe organ dysfunction. Flavone chrysin is one of the indispensable biological active ingredients for different fruits and vegetables and has antioxidant and anti-inflammatory properties. However, it is not clear whether chrysin is an effective treatment for heart dysfunction caused by sepsis. We found that it had protective effects against the harmful effects caused by LPS, manifested in improved survival, normalized cardiac function, improved partial pathological scores of myocardial tissue, and remission of apoptosis, as well as reduced oxidative stress and inflammation. Mechanism studies have found that chrysin is an important antioxidant protein, a key regulator of heme oxygenase 1 (HO-1). We found that HO-1 levels were increased after LPS intervention, and chrysin further increased HO-1 levels, along with the addition of Nrf2, a regulator of antioxidant proteins. Pretreatment with PD98059, an extracellular signal-regulated kinase-specific inhibitor, blocked chrysin-mediated phosphorylation of Nrf2 and the nuclear translocation of Nrf2. The protective effect of chrysin on sepsis-induced cardiac dysfunction was blocked by ZnPP, which is a HO-1 blocker. Chrysin increased antioxidant activity and reduced markers of oxidative stress (SOD and MDA) and inflammation (MPO and IL-1β), all of which were blocked by ZnPP. This indicates that HO-1 is the upstream molecule regulating the protective effect of chrysin. Thus, by upregulation of HO-1, chrysin protects against LPS-induced cardiac dysfunction and inflammation by inhibiting oxidative stress.
MiR-129-5p Protects H9c2 Cardiac Myoblasts From Hypoxia/Reoxygenation Injury by Targeting TRPM7 and Inhibiting NLRP3 Inflammasome Activation
Authors: Liu Shuke , Liao Qingchi , Xu Wei , Zhang Zhen , Yin Minming , Cao Xiaohu
Published: March 2021

As a biomarker for heart failure, miR-129-5p is abnormally expressed during myocardial I/R, but its specific functions and mechanisms remain largely unclear. Thus, this study explored the roles and possible mechanisms of miR-129-5p in hypoxia/reoxygenation (H/R)-insulted H9c2 cardiac myoblasts. After H/R insult, miR-129-5p expression levels were decreased, along with reduced cell viability and enhanced lactate dehydrogenase release in H9c2 cells. Overexpression of miR-129-5p through transfection of miR-129-5p mimics effectively improved cell viability and reduced lactate dehydrogenase release in H9c2 cells exposed to H/R, along with decreased apoptosis and caspase-3 activities. Moreover, miR-129-5p mimics inhibited reactive oxygen species production and upsurged superoxide dismutase activity in H9c2 cells exposed to H/R, and suppressed H/R-caused massive release of proinflammatory cytokines TNF-α and IL-1β. TRPM7 was identified as the target of miR-129-5p and was negatively regulated by miR-129-5p. TRPM7 overexpression counteracted the antagonistic effect of miR-129-5p on H/R-induced increase in intracellular calcium levels. TRPM7 overexpression also abolished miR-129-5p-induced elevation on cell viability and reduction on apoptosis as well as attenuated miR-129-5p-induced inhibition on reactive oxygen species and IL-1β production. Besides, H/R-induced NLRP3 inflammasome activation was inhibited by miR-129-5p mimic but reactivated by TRPM7. In conclusion, miR-129-5p alleviates H/R injury of H9c2 cardiomyocytes by targeting TRPM7 and inhibiting NLRP3 inflammasome activation, suggesting that miR-129-5p and TRPM7 may be potential therapeutic targets for myocardial I/R injury.
Circulating PGLYRP1 Levels as a Potential Biomarker for Coronary Artery Disease and Heart Failure
Authors: Han Yanxin , Hua Sha , Chen Yanjia , Yang Wenbo , Zhao Weilin , Huang Fanyi , Qiu Zeping , Yang Chendie , Jiang Jie , Su Xiuxiu , Yang Ke , Jin Wei
Published: March 2021

Coronary artery disease (CAD) and associated comorbidities such as heart failure (HF) remain the leading cause of morbidity and mortality worldwide attributed to, at least partially, the lack of biomarkers for efficient disease diagnosis. Here, we evaluated the diagnostic potential of serum peptidoglycan recognition protein 1 (PGLYRP1), an important component of the innate immunity and inflammation system, for both CAD and HF. A machine-learning method (random forest) was used to evaluate the clinical utility of circulating PGLYRP1 for diagnosis of CAD and HF in a total of 370 individuals. Causal links of chronic serum PGLYRP1 elevation to both diseases were further explored in ApoE−/− mice. The serum levels of PGLYRP1 were significantly higher in individuals with either chronic CAD or acute coronary syndrome than those in those without coronary artery stenosis (the control group) and even more pronounced in CAD individuals with concomitant HF. Our random forest classifier revealed that this protein performed better than other recommended clinical indicators in distinguishing the CAD from the control individuals. In addition, this protein associates more with the biomarkers of HF including left ventricular ejection fraction than inflammation. Notably, our mice experiment indicated that long-term treatment with recombinant PGLYRP1 could significantly impair the cardiovascular system as reflected from both increased atherogenic lesions and reduced fractional shortening of the left ventricle. Our findings, therefore, supported the circulating levels of PGLYRP1 as a valuable biomarker for both CAD and HF.
The Angiotensin II Type 1(AT1) Receptor and Cardiac Hypertrophy: Did We Have It Wrong All Along?
Authors: Zouein Fouad A. , Altara Raffaele , Massoud Gaelle P. , Booz George W.
Published: March 2021

An ongoing issue in cardiac pharmacology is whether angiotensin II has direct growth promoting effects on the heart via the angiotensin II type 1 (AT1) receptor. This question has relevance for whether angiotensin-converting enzyme inhibitors and AT1 receptor blockers offer additional benefit in preventing adverse cardiac remodeling in hypertension. In a recent study, 2 strains of mice were infused with angiotensin II. In both, AT1 receptors were deleted in the heart and conduit vessels, but in one, AT1 receptors were also deleted in resistance vessels. Angiotensin II caused hypertrophy and hypertension in the strain lacking AT1 receptors in the heart and conduit vessels, but not in the strain without AT1 receptors in resistance vessels. This finding supports the conclusion that blood pressure is more important in determining cardiac hypertrophy than direct AT1 activation by angiotensin II, when the two are rapidly and simultaneously introduced. Surprisingly, mice with no cardiac AT1 receptor expression developed ventricular dilation and eccentric hypertrophy with pressure overload, in contrast to wild type mice that exhibited concentric hypertrophy, suggesting that cardiac AT1 receptors protect against high blood pressure. This interpretation revives issues related to β–arrestin-biased signaling and mechanosensitivity of AT1 receptors. Synthetic nanobodies, which are based on the variable regions of camelid-derived heavy chain–only antibodies, could be applied to explore the therapeutic potential of exploiting different activation states of AT1 under stress conditions, such as hypertension and heart failure. At the very least, this experimental approach is likely to reveal new facets of AT1 receptor signaling in the heart.
Adverse Effects of Oseltamivir Phosphate Therapy on the Liver of LDLR−/− Mice Without Any Benefit on Atherosclerosis and Thrombosis
Authors: Bocquet Olivier , Wahart Amandine , Sarazin Thomas , Vincent Elise , Schneider Christophe , Fougerat Anne , Gayral Stéphanie , Henry Aubéri , Blaise Sébastien , Romier-Crouzet Béatrice , Boulagnon Camille , Jaisson Stéphane , Gillery Philippe , Bennasroune Amar , Sartelet Hervé , Laffargue Muriel , Martiny Laurent , Duca Laurent , Maurice Pascal
Published: March 2021

Desialylation, governed by sialidases or neuraminidases, is strongly implicated in a wide range of human disorders, and accumulative data show that inhibition of neuraminidases, such as neuraminidases 1 sialidase, may be useful for managing atherosclerosis. Several studies have reported promising effects of oseltamivir phosphate, a widely used anti-influenza sialidase inhibitor, on human cancer cells, inflammation, and insulin resistance. In this study, we evaluated the effects of oseltamivir phosphate on atherosclerosis and thrombosis and potential liver toxicity in LDLR−/− mice fed with high-fat diet. Our results showed that oseltamivir phosphate significantly decreased plasma levels of LDL cholesterol and elastin fragmentation in aorta. However, no effect was observed on both atherosclerotic plaque size in aortic roots and chemically induced thrombosis in carotid arteries. Importantly, oseltamivir phosphate administration had adverse effects on the liver of mice and significantly increased messenger RNA expression levels of F4/80, interleukin-1β, transforming growth factor-β1, matrix metalloproteinase-12, and collagen. Taken together, our findings suggest that oseltamivir phosphate has limited benefits on atherosclerosis and carotid thrombosis and may lead to adverse side effects on the liver with increased inflammation and fibrosis.
Coronary artery disease prediction based on breast arterial calcification in women undergoing mammography as a screening for breast cancer
Authors: Pudil Jan , Steyerová Petra , Macová Iva , Zemánek David , Král Aleš , Pad’our Michal , Chen Zhi , Daneš Jan , Kovárník Tomáš
Published: March 2021

Objective:

The aim of the study was to test the potential role of breast arterial calcification (BAC) in the prediction of coronary artery disease (CAD) in women. The criterion standard for CAD diagnostics was coronary angiography.

Methods:

This retrospective study enrolled 163 consecutive women, who underwent digital mammography and coronary angiography in our hospital. We assessed the presence and severity of BAC, and tested whether the presence and/or extent of BAC could be a predictor for CAD, quantified by Gensini score.

Results:

BAC was presented in 34 patients (21%). Neither the presence of CAD (17 patients, 50%, vs 55 42.6%, P = 0.44), nor the Gensini score (20.5 ± 29.7 vs 15.4 ± 24.1, P = 0.3) differed significantly between BAC-present and BAC-absent patients.

A finding of triple-vessel disease, however, more frequently occurred in the BAC-present (seven patients, 20.6%) than in the BAC-absent (nine patients, 7%) group, odds ratio (OR) 3.1, 95% CI 1-9.5, P = 0.049. The presence of BAC did not significantly increase the odds for the presence of CAD (OR = 1.29, P = 0.54). Among the subgroup of patients with CAD, BAC presence was associated with triple vessel disease (OR = 3.34, P = 0.049).

Conclusions:

We did not confirm BAC as a predictor of CAD. However, BAC showed association with more severe forms of coronary atherosclerosis (triple vessel disease).

Video Summary:

http://links.lww.com/MENO/A728.
Demographic and Cultural Differences in the Acceptance and Pursuit of Cosmetic Surgery: A Systematic Literature Review
Authors: Alotaibi Ahmed S.
Published: March 2021

Background:

Worldwide, the numbers of cosmetic procedures continue to climb. However, cosmetic surgery (CS) continues to be plagued by negative stigmatization. This study reviews the literature to identify how attitudes toward CS vary by sex, age, race, culture, and nationality, and aims to determine how other factors like media exposure interact with demographics to influence how well CS is accepted.

Methods:

A PRISMA-guided systematic review of the literature was conducted to identify all English-language papers reporting on CS or plastic surgery acceptance, attitudes, or stigmatization, specifically examining for data on age, sex, race/ethnicity, culture, and media influence.

Results:

In total, 1515 abstracts were reviewed, of which 94 were deemed pertinent enough to warrant a full-text review. Among the potential demographic predictors of CS acceptance, the one with the most supportive data is sex, with women comprising roughly 90% of all CS patients in virtually all populations studied and consistently exhibiting greater CS knowledge and acceptance. Culturally, the pursuit of beauty through CS is a universal phenomenon, although different countries, races, and cultures differ in how willingly CS is embraced, and in the aesthetic goals of those choosing to have it. In countries with culturally diverse societies like the United States, non-Hispanic Whites continue to predominate among CS patients, but the number of CS patients of other races is rising disproportionately. In this trend, social media is playing a major role.

Conclusion:

Healthcare practitioners performing cosmetic procedures need to consider demographic and cultural differences of the patients in order to enhance their understanding of their patients’ aesthetic goals and expectations.
Agreement of emergency physician-performed ultrasound versus RADiology-performed UltraSound for cholelithiasis or cholecystitis: a systematic review
Authors: Dupriez Florence , Geukens Paul , Penaloza Andrea , Vanpee Dominique , Bekkering Geertruida , Bobbia Xavier
Published: March 2021

Cholecystitis secondary to gallstone migration is the most common suspected diagnosis for right upper quadrant pain in emergency departments, with radiology-performed ultrasound (RADUS) being the main diagnostic tool. The primary aim of this review was to assess the ability of emergency physicians to perform emergency ultrasound (EUS) compared to RADUS to diagnose cholelithiasis and cholecystitis. A systematic search was performed using Embase, Central (Cochrane library), Web of Science, MEDLINE, Google Scholar, prospective trial registries, and OpenSIGLE databases as well as hand-search of articles. Two physicians independently selected the articles. Assessment of methodological quality was performed using the Quality Assessment of Diagnostic Accuracy Studies 2 tool. Clinical and methodological heterogeneity were qualitatively reported and discussed. Seven prospective studies were selected involving a total of 1061 subjects undergoing EUS. The included studies all used RADUS as the reference standard and emergency physician-performed EUS as the index test. Included studies mostly reported diagnostic accuracy for cholelithiasis diagnosis whereas only one study mentioned diagnostic accuracy for cholecystitis. Clinical and methodological heterogeneity between included studies prevented a meta-analysis. This review shows there is good agreement between EUS and RADUS to assess the gallbladder for cholelithiasis and therefore supports its use by emergency physicians for that matter. Nevertheless, this work identified clinical and methodological heterogeneity along with a poor description EUS operators’ experience. In the future, larger studies should include a larger population of EUS operators, specify their background, and compare EUS to the final diagnosis to evaluate performances for gallbladder diagnostic accuracy.
Payment Discrepancies and Access to Primary Care Physicians for Dual-eligible Medicare-Medicaid Beneficiaries
Authors: Fung Vicki , McCarthy Stephen , Price Mary , Hull Peter , Lê Cook Benjamin , Hsu John , Newhouse Joseph P.
Published: March 2021

Background:

Physicians often receive lower payments for dual-eligible Medicare-Medicaid beneficiaries versus nondual Medicare beneficiaries because of state reimbursement caps. The Affordable Care Act (ACA) primary care fee bump temporarily eliminated this differential in 2013–2014.

Objective:

To examine how dual payment policy impacts primary care physicians’ (PCP) acceptance of duals.

Research Design:

We assessed differences in the likelihood that PCPs had dual caseloads of ≥10% or 20% in states with lower versus full dual reimbursement using linear probability models adjusted for physician and area-level traits. Using a triple-difference approach, we examined changes in dual caseloads for PCPs versus a control group of specialists in states with fee bumps versus no change during years postbump versus prebump.

Subjects:

PCPs and specialists (cardiologists, orthopedic surgeons, general surgeons) that billed fee-for-service Medicare.

Measures:

State dual payment policies and physicians’ dual caseloads as a percentage of their Medicare patients.

Results:

In 2012, 81% of PCPs had dual caseloads of ≥10% and this was less likely among PCPs in states with lower versus full dual reimbursement (eg, difference=−4.52 percentage points; 95% confidence interval, −6.80 to −2.25). The proportion of PCPs with dual caseloads of ≥10% or 20% decreased significantly between 2012 and 2017 and the fee bump was not consistently associated with increases in dual caseloads.

Conclusions:

Pre-ACA, PCPs’ participation in the dual program appeared to be lower in states with lower reimbursement for duals. Despite the ACA fee bump, dual caseloads declined over time, raising concerns of worsening access to care.
Sex-specific costs of reproduction on survival in a long-lived seabird
Authors: Cruz-Flores Marta , Pradel Roger , Bried Joël , González-Solís Jacob , Ramos Raül
Published: March 2021

Costs of reproduction on survival have captured the attention of researchers since life history theory was formulated. Adults of long-lived species may increase survival by reducing their breeding effort or even skipping reproduction. In this study, we aimed to evaluate the costs of current reproduction on survival and whether skipping reproduction increases adult survival in a long-lived seabird. We used capture–mark–recapture data (1450 encounters) from two populations of Bulwer's petrel (
Bulweria bulwerii
), breeding in the Azores and Canary Islands, North Atlantic Ocean. Using a multi-event model with two different breeding statuses (breeders versus non-breeders), we calculated probabilities of survival and of transitions between breeding statuses, evaluating potential differences between sexes. Females had lower survival probabilities than males, independent of their breeding status. When considering breeding status, breeding females had lower survival probabilities than non-breeding females, suggesting costs of reproduction on survival. Breeding males had higher survival probabilities than non-breeding males, suggesting that males do not incur costs of reproduction on survival and that only the highest quality males have access to breeding. The highest and the lowest probabilities of skipping reproduction were found in breeding males from the Azores and in breeding males from the Canary Islands, respectively. Intermediate values were observed in the females from both populations. This result is probably due to differences in the external factors affecting both populations, essentially predation pressure and competition. The existence of sex-specific costs of reproduction on survival in several populations of this long-lived species may have important implications for species population dynamics.