bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Review of the Empirical Literature on Audit Market Concentration
Authors: Elbardan Hany , Kotb Amr , Ishaque Maria 
Published: February 2023

Synopsis The research problem The extant audit market concentration (AMC) literature is quite scattered, which makes it challenging to comprehend the current state of knowledge and to highlight the areas that require further exploration. An improved understanding of AMC and its possible effects require a comprehensive review of the AMC literature, since no such review has yet been published. Therefore, our paper intends to: (a) synthesize the empirical work in the AMC literature; (b) determine the limitations in the ways AMC has been investigated; (c) identify avenues of inquiry that could guide future thinking on AMC; and (d) develop insights into how future AMC investigations can be further developed. Motivation The most noticeable developments in AMC occurred after the audit firm megamergers of the 1980s and 1990s and Andersen’s demise in 2002. This trend toward fewer and larger suppliers of auditing services has sparked intense debate about the costs and benefits of AMC. However, the literature provides mixed evidence on the determinants and consequences of AMC. Adopted methodology A structured literature review [Massaro, M., Dumay, J., & Guthrie, J. (2016). On the shoulders of giants: Undertaking a structured literature review. Accounting, Auditing and Accountability Journal, 29(5), 767–801. https://doi.org/10.1108/AAAJ-01-2015-1939 ] was employed to review the extant AMC literature. Analyses We analyzed 108 empirical papers published in 39 peer-reviewed quality accounting and auditing journals in the English language over a 55-year period (1967 to mid-2021). Findings The analysis suggests a consistent rise in AMC levels, leading to a tight oligopoly and, in rare cases, to a duopoly, across countries and over time. Studies of audit pricing and audit quality comprise the predominant part of the literature, and these report mixed findings as to whether AMC facilitates monopolistic pricing and allows audit-quality-threatening behaviors. This could be attributed to several factors, including the focus on short-term effects of AMC; substantial variations in how concentration was measured; and misguided use of proxies for audit competition and audit quality. The review identifies four key limitations that circumscribe our understanding of AMC: (a) the lack of investigation into the actual dynamic rivalry among audit firms; (b) great reliance on the positivistic approach and quantitative methods, and the lack of use of explicit theories aside from economic theories; (c) a focus on the audit of publicly listed companies in the United States, the U.K., and Australia; and thus; (d) the absence of key organizational settings and central regions in the AMC debate. To counter these limitations, this review puts forward possible future research avenues that can help to advance our understanding of AMC to address emerging challenges in the field.
Effects of miR-107 on Breast Cancer Cell Growth and Death via Regulation of the PTEN/AKT Signaling Pathway
Authors: Pan Hua , Peng Hongwei , Dai Yun , Han Bin , Yang Guangming , Jiang Nian , Zhou Ping 
Published: February 2023

Objective. Investigate the influence of miR-107 on breast cancer cell growth and death through the PTEN/AKT signaling pathway. Method. As study subjects, the human breast cancer cell line MCF-7 and the normal breast cell line Hs 578Bst were chosen, and MCF-7 cells were, respectively, transfected with control miRNA and miR-107 inhibitor. CCK-8, flow cytometry, scratch assay, and Transwell assay were used to analyze the proliferation, apoptosis, and invasion, and in order to identify the proteins associated with apoptosis in each of the three categories, we used western blot analysis. Bcl-2, cleaved caspase-3, and cleaved caspase-9 expression, as well as PTEN/AKT signaling pathway-associated protein expression, are correlated. Result. The expression of miR-107 in MCF-7 cells was significantly greater than that in Hs 578Bst cells, with a

P

< 0.05 difference; compared to the blank and miRNA control groups, the miR-107 inhibitor group had a

P

< 0.05 difference.

P

< 0.05 showed a decrease in proliferation (42.52) but no difference in proliferation between the blank and miRNA control groups (

P

> 0.05); the miR-107 inhibitor group had higher apoptosis (38.96) with

P

< 0.05 than the blank group (4.85) and the miRNA control group (5.89); there was no difference in apoptosis between the blank and miRNA groups (

P

> 0.05). There was no significant difference between the blank group and the miRNA control group with

P

> 0.05; compared with the blank group, the miR-107 inhibitor group had a lower expression of Bcl-2 protein (0.18), in addition to the degraded paradigms (0.73) and caspase-9 protein concentrations (0.79), respectively. Conclusion. The PTEN/AKT signaling pathway may be regulated by miR-107 to limit breast cancer cell growth and increase apoptosis, which suggests that miR-107 may be exploited as a tumor marker for therapeutic therapy.
Inhibitor of Apoptosis Proteins Antagonist Induces T-cell Proliferation after Cross-Presentation by Dendritic Cells
Authors: Hoefsmit Esmée P. , van Royen Paula T. , Rao Disha , Stunnenberg Johanna A. , Dimitriadis P. , Lieftink Cor , Morris Ben , Rozeman Elisa A. , Reijers Irene L.M. , Lacroix Ruben , Shehwana Huma , Ligtenberg Maarten A. , Beijersbergen Roderick L. , Peeper Daniel S. , Blank Christian U. 
Published: February 2023

AbstractCross-presentation of tumor antigens by dendritic cells (DC) is crucial to prime, stimulate and restimulate CD8+ T cells. This process is important in initiating and maintaining an antitumor response. Here, we show that the presence of conventional type 1 DCs (cDC1), a DC subtype that excels in cross-presentation, in the tumor correlated with response to neoadjuvant immune checkpoint blockade (ICB) in melanoma. This led us to hypothesize that patients failing to respond to ICB could benefit from enhanced cross-presentation of tumor antigens. We therefore established a cross-presentation assay to screen over 5,500 compounds for enhancers of DC cross-presentation using induced T-cell proliferation as the readout. We identified 145 enhancers, including AZD5582, an antagonist of inhibitor of apoptosis proteins (IAP) cIAP1, cIAP2, and XIAP. AZD5582 treatment led to DC activation of the noncanonical NF-kB pathway, enhanced antigen import from endolysosomes into the cytosol, and increased expression of genes involved in cross-presentation. Furthermore, it upregulated expression of CD80, CD86, MHC class II, CD70 and secretion of TNF by DCs. This enhanced DC activation and maturation program was observed also in tumor-bearing mice upon AZD5582 treatment, culminating in an increased frequency of systemic tumor antigen–specific CD8+ T cells. Our results merit further exploration of AZD5582 to increase antigen cross-presentation for improving the clinical benefit of ICB in patients who are unlikely to respond to ICB.
Altered Neuronal Discharge in the Organum Vasculosum of the Lamina Terminalis Contributes to Dahl Salt-Sensitive Hypertension
Authors: Stocker Sean D. 
Published: February 2023

Background:
Salt-sensitive hypertension in humans and experimental models is associated with higher plasma and cerebrospinal fluid sodium chloride (NaCl) concentrations. Changes in extracellular NaCl concentrations are sensed by specialized neurons in the organum vasculosum of the lamina terminalis (OVLT). Stimulation of OVLT neurons increases sympathetic nerve activity (SNA) and arterial blood pressure (ABP), whereas chronic activation produces hypertension. Therefore, the present study tested whether OVLT neuronal activity was elevated and contributed to SNA and ABP in salt-sensitive hypertension.

Methods:
Male Dahl salt-sensitive (Dahl S) and Dahl salt-resistant (Dahl R) rats were fed 0.1% or 4.0% NaCl diets for 3 to 4 weeks and used for single-unit recordings of OVLT neurons or simultaneous recording of multiple sympathetic nerves during pharmacological inhibition of the OVLT.

Results:
Plasma and cerebrospinal fluid Na+ and Cl− concentrations were higher in Dahl S rats fed 4% versus 0.1% or Dahl R rats fed either diet. In vivo single-unit recordings revealed a significantly higher discharge of NaCl-responsive OVLT neurons in Dahl S rats fed 4% versus 0.1% or Dahl R rats. Interestingly, intracarotid infusion of hypertonic NaCl evoked greater increases in OVLT neuronal discharge of Dahl S versus Dahl R rats regardless of NaCl diet. The activity of non–NaCl-responsive OVLT neurons was not different across strain or diets. Finally, inhibition of OVLT neurons by local injection of the gamma-aminobutyric acid agonist muscimol produced a greater decrease in renal SNA, splanchnic SNA, and ABP of Dahl S rats fed 4% versus 0.1% or Dahl R rats.

Conclusions:
A high salt diet activates NaCl-responsive OVLT neurons to increase SNA and ABP in salt-sensitive hypertension.
Informing Use of Telehealth for Managing Chronic Conditions: Mixed‐Methods Evaluation of Telehealth Use to Manage Heart Failure During COVID‐19
Authors: Leonard Chelsea , Liu Wenhui , Holstein Ariel , Alliance Slande , Nunnery Mary , Rohs Carly , Sloan Marilyn , Winchester David E. 
Published: February 2023

Background
The COVID‐19 pandemic forced Veterans Health Administration facilities to rapidly adopt and deploy telehealth alternatives to provide continuity of care to veterans while minimizing physical contact. The impact of moving to virtual visits on patients with congestive heart failure (HF) is unknown. The goal of this study was to understand how patients with HF and their providers experienced the shift to telehealth for managing a chronic condition, and to inform best practices for continued telehealth use.

Methods and Results
We identified Veterans Health Administration Medical Centers with high telehealth use before COVID‐19 and sites that were forced to adopt telehealth in response to COVID‐19, and interviewed cardiology providers and veterans with HF about their experiences using telehealth. Interviews were recorded, transcribed, and analyzed using team‐based rapid content analysis. We identified 3 trajectory patterns for cardiology telehealth use before and during COVID‐19. They were the low‐use class (low to low), high‐use class (relatively high to higher), and increased‐use class (low to high). The high‐use and increased‐use classes fit the criteria for sites that had high telehealth use before COVID‐19 and sites that rapidly adopted telehealth in response to COVID‐19. There were 12 sites in the high‐use class and 4 sites in the increased‐use class. To match with the number of sites in the increased‐use class, we selected the top 4 sites by looking at the months before COVID‐19. We identified 3 themes related to telehealth use among patients with HF and cardiology providers: (1) technology was the primary barrier for both patients and providers; (2) infrastructural support was the primary facilitator for providers; and (3) both patients and providers had largely neutral opinions on how telehealth compares to in‐person care but described situations in which telehealth is not appropriate.

Conclusions
Only 12 sites fit the criteria of high telehealth use in cardiology before COVID‐19, and 4 fit the criteria of low use that increased in response to COVID‐19. Patients and providers at both site types were largely satisfied using telehealth to manage HF. Understanding best practices for managing ambulatory care–sensitive conditions through virtual visits can help the Veterans Health Administration prepare for long‐term impacts of COVID‐19 on in‐person visits, as well as improve access to care for veterans who live remotely or who have difficulty traveling to in‐person appointments.
Association Between Measures of Body Composition and Coronary Calcium: Findings From the Multi‐Ethnic Study of Atherosclerosis
Authors: Horwich Tamara , Srikanthan Preethi , Gaitonde Anisha , Watson Karol , Allison Matthew , Kronmal Richard 
Published: February 2023

Background
Obesity, as measured by body mass index, is widely recognized as a risk factor for the development of cardiovascular disease. However, the role of body composition components such as fat and lean mass is not well studied.

Methods and Results

A total of 3129 patients who underwent computed tomography scans for quantification of coronary artery calcification and had bioelectrical impedance analysis of body composition (fat mass and fat‐free mass) during exam 5 of MESA (Multi‐Ethnic Study of Atherosclerosis) were included in this cross‐sectional analysis. Multivariable adjusted linear regression analysis was performed to assess the relationship between both fat mass and fat‐free mass to prevalent coronary artery calcification, a marker of subclinical coronary artery disease quantified by both the coronary artery calcification (CAC) Agatston score and the spatially weighted calcium score. CAC and spatially weighted calcium score were natural log–transformed for analysis as continuous variables. Fat‐free mass, but not fat mass, was independently associated with CAC. There was a 7.6% prevalence risk difference for CAC>0 per 10 kg. Fat‐free mass was also significantly associated with natural log of CAC (coefficient=0.272,
P
<0.001). Both fat‐free mass and fat mass were positively associated with natural log of spatially weighted calcium score, with risk difference coefficients of 0.729 and 0.359, respectively (
P
<0.001).

Conclusions
In this cross‐sectional study, higher lean mass by bioelectrical impedance analysis and, to a lesser extent, higher fat mass by bioelectrical impedance analysis were significantly associated with higher coronary calcium, a marker of subclinical cardiovascular disease. Further exploration of the relationship between components of body composition and the development of cardiovascular disease is warranted.
Chymase Inhibition Resolves and Prevents Deep Vein Thrombosis Without Increasing Bleeding Time in the Mouse Model
Authors: Lapointe Catherine , Vincent Laurence , Giguère Hugo , Auger‐Messier Mannix , Schwertani Adel , Jin Denan , Takai Shinji , Pejler Gunnar , Sirois Martin G. , Tinel Hanna , Heitmeier Stefan , D'Orléans‐Juste Pedro 
Published: February 2023

Background
Deep vein thrombosis (DVT) is the primary cause of pulmonary embolism and the third most life‐threatening cardiovascular disease in North America. Post‐DVT anticoagulants, such as warfarin, heparin, and direct oral anticoagulants, reduce the incidence of subsequent venous thrombi. However, all currently used anticoagulants affect bleeding time at various degrees, and there is therefore a need for improved therapeutic regimens in DVT. It has recently been shown that mast cells play a crucial role in a DVT murine model. The underlying mechanism involved in the prothrombotic properties of mast cells, however, has yet to be identified.

Methods and Results

C57BL/6 mice and mouse mast cell protease‐4 (mMCP‐4) genetically depleted mice (mMCP‐4 knockout) were used in 2 mouse models of DVT, partial ligation (stenosis) and ferric chloride–endothelial injury model of the inferior vena cava. Thrombus formation and impact of genetically repressed or pharmacologically (specific inhibitor TY‐51469) inhibited mMCP‐4 were evaluated by morphometric measurements of thrombi immunochemistry (mouse and human DVT), color Doppler ultrasound, bleeding times, and enzymatic activity assays ex vivo
.
Recombinant chymases, mMCP‐4 (mouse) and CMA‐1 (human), were used to characterize the interaction with murine and human plasmin, respectively, by mass spectrometry and enzymatic activity assays. Inhibiting mast cell–generated mMCP‐4, genetically or pharmacologically, resolves and prevents venous thrombus formation in both DVT models. Inferior vena cava blood flow obstruction was observed in the stenosis model after 6 hours of ligation, in control‐ but not in TY‐51469–treated mice. In addition, chymase inhibition had no impact on bleeding times of healthy or DVT mice. Furthermore, endogenous chymase limits plasmin activity in thrombi ex vivo. Recombinant mouse or human chymase degrades/inactivates purified plasmin in vitro. Finally, mast cell–containing immunoreactive chymase was identified in human DVT.

Conclusions
This study identified a major role for mMCP‐4, a granule‐localized protease of chymase type, in DVT formation. These findings support a novel pharmacological strategy to resolve or prevent DVT without affecting the coagulation cascade through the inhibition of chymase activity.
Impact of Peripheral Artery Disease in Patients With Heart Failure Undergoing Transcatheter Mitral Valve Repair: The COAPT Trial
Authors: Shahim Bahira , Cohen David J. , Ben‐Yehuda Ori , Redfors Björn , Kar Saibal , Lim D. Scott , Arnold Suzanne V. , Li Yanru , Lindenfeld JoAnn , Abraham William T. , Mack Michael J. , Stone Gregg W. 
Published: February 2023

Background
Peripheral artery disease (PAD) and heart failure (HF) often coexist. Whether PAD influences outcomes of transcatheter mitral valve repair (TMVr) in patients with HF and severe secondary mitral regurgitation is unknown. The objectives are to assess the impact of PAD on outcomes of TMVr plus guideline‐directed medical therapy (GDMT) versus GDMT alone in patients with HF and secondary mitral regurgitation.

Methods and Results

The COAPT trial (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients with Functional Mitral Regurgitation) randomized patients with HF with ≥moderate‐to‐severe secondary mitral regurgitation to TMVr with MitraClip implant plus GDMT versus GDMT alone. We evaluated the relationship between PAD and 2‐year outcomes in
the COAPT trial
and examined whether PAD modified the benefits of TMVr. Among 614 patients enrolled, 109 (17.8%) had PAD. By multivariable analysis, PAD was independently associated with 2‐year mortality (adjusted hazard ratio [adjHR], 1.51 [95% CI, 1.07–2.15]) but not HF hospitalizations. Compared with GDMT alone, TMVr reduced the 2‐year risk of death in patients without PAD (adjHR, 0.42 [95% CI, 0.30–0.60]) but not those with PAD (adjHR, 1.27 [95% CI, 0.72–2.27];
P
interaction
=0.001). In contrast, TMVr reduced HF hospitalizations consistently in patients with (adjHR, 0.65 [95% CI, 0.35–1.23]) and without (adjHR, 0.42 [95% CI, 0.31–0.57]) PAD (
P
interaction
=0.22). Improvements in health status and exercise capacity at 2 years with TMVr compared with GDMT alone were similar in degree, irrespective of PAD status (
P
interaction
=0.76 and 0.64, respectively).

Conclusions
In patients with HF and severe secondary mitral regurgitation, the reduced mortality with TMVr in the overall COAPT study population was not observed in the subgroup of patients with PAD. However, TMVr reduced HF hospitalizations and improved health status and exercise capacity consistently in patients with and without PAD.

Registration

Clinical Trial Name: Cardiovascular Outocmes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients with Functional Mitral Regurgitation (The COAPT Trial); URL:
https://www.clinicaltrials.gov/
; Unique identifier: NCT01626079.
https://clinicaltrials.gov/ct2/show/NCT01626079
Long-Term Trends of the Atmospheric Circulation and Moist Static Energy Budget in the JRA-55 Reanalysis
Authors: Franzke Christian L. E. , Harnik Nili 
Published: February 2023

Abstract
The atmospheric circulation response to global warming is an important problem that is theoretically still not well understood. This is a particular issue since climate model simulations provide uncertain, and at times contradictory, projections of future climate. In particular, it is still unclear how a warmer and moister atmosphere will affect midlatitude eddies and their associated poleward transport of heat and moisture. Here we perform a trend analysis of three main components of the global circulation—the zonal-mean state, eddies, and the net energy input into the atmosphere—and examine how they relate in terms of a moist static energy budget for the JRA-55 reanalysis data. A particular emphasis is made on understanding the contribution of moisture to circulation trends. The observed trends are very different between the hemispheres. In the Southern Hemisphere there is an overall strengthening and during boreal summer, also a poleward shifting, of the jet stream, the eddies, and the meridional diabatic heating gradients. Correspondingly, we find an overall strengthening of the meridional gradients of the net atmospheric energy input. In the Northern Hemisphere, the trend patterns are more complex, with the dominant signal being a clear boreal winter Arctic amplification of positive trends in lower-tropospheric temperature and moisture, as well as a significant weakening of both bandpass and low-pass eddy heat and moisture fluxes. Consistently, surface latent and sensible heat fluxes, upward and downward longwave radiation, and longwave cloud radiative fluxes at high latitudes show significant trends. However, radiative fluxes and eddy fluxes are inconsistent, suggesting data assimilation procedures need to be improved.

Significance Statement
We use a long-term reanalysis dataset to get an overall view of the changes in the global circulation and its role in transporting moist static energy from the equator to the poles. We do this by examining the trends in its three main components—the zonal means, the eddies, and the net energy input into the atmosphere. We find that in the Southern Hemisphere, there is an overall strengthening of the eddies, their poleward energy fluxes, and correspondingly the meridional gradients of the net atmospheric energy input. In the Northern Hemisphere, though the pattern is more complex, there is an overall weakening of the eddies and poleward eddy fluxes, and of the meridional gradients of the net atmospheric energy input, consistent with Arctic warming.