bluuebunny/crossref_metadata_2025_split huggingface dataset:
Balance Sheet Debt Covenants and Seasoned Equity Offerings
Authors: Malikov Kamran T. 
Published: May 2024

Synopsis The research problem This study examined the effect of having debt contracts that contain balance sheet covenants on the decision to make seasoned equity offerings (SEOs). Motivation Prior studies examined the determinants of equity issuance without considering private debt contracts that contain balance sheet covenants. Generally, firms are not restricted from stock issuance when they have financial debt covenants. This might motivate firms to make SEOs when they are more susceptible to balance sheet debt covenant violations. Making SEOs increases firms’ equity capitals in the short term and, therefore, has the direct effect of improving balance sheet covenants in the current period. This effect motivated this study to examine whether firms are more likely to conduct SEOs when their debt contracts include more-restrictive balance sheet covenants. The test hypothesis The hypothesis of the study is in the null form, which states that balance sheet covenant restrictiveness is unrelated to the probability of conducting SEOs. Target population The target population includes shareholders, debtholders, and firm managers. Adopted methodology Panel data estimation was used, specifically, the fixed effects model. Analyses The empirical analysis was conducted on a unique sample of UK listed firms with private debt covenants that is hand-collected from annual reports. Equity issuance in the sample is based on private placements, which are a common type of SEO in the UK. The restrictiveness of balance sheet-based covenants is defined as the number of balance sheet covenants in a loan contract or the tightness of net worth covenant slack. Findings The results show that balance sheet covenant restrictiveness is positively associated with the probability of conducting SEOs through private placements. The baseline result is robust to the application of a number of the controls often used in the literature, including cash shortage, the use of balance sheet covenants in the previous loan contract, earnings management, and the quality of external governance. It is also robust to excluding the financial crisis period and addressing potential endogeneity concerns using a propensity score-matching procedure. Additionally, further analysis provides some evidence that equity issuance by firms with more-restrictive balance sheet covenants is negatively associated with future operating performance, suggesting that these firms may not efficiently use the raised capital.
Association of Aortic Stiffness and Pressure Pulsatility With Noninvasive Estimates of Hepatic Steatosis and Fibrosis: The Framingham Heart Study
Authors: Cooper Leroy L. , Prescott Brenton R. , Xanthakis Vanessa , Benjamin Emelia J. , Vasan Ramachandran S. , Hamburg Naomi M. , Long Michelle T. , Mitchell Gary F. 
Published: May 2024

BACKGROUND:
Arterial stiffening may contribute to the pathogenesis of metabolic dysfunction–associated steatotic liver disease. We aimed to assess relations of vascular hemodynamic measures with measures of hepatic steatosis and fibrosis in the community.

METHODS:
Our sample was drawn from the Framingham Offspring, New Offspring Spouse, Third Generation, Omni-1, and Omni-2 cohorts (N=3875; mean age, 56 years; 54% women). We used vibration-controlled transient elastography to assess controlled attenuation parameter and liver stiffness measurements as measures of liver steatosis and liver fibrosis, respectively. We assessed noninvasive vascular hemodynamics using arterial tonometry. We assessed cross-sectional relations of vascular hemodynamic measures with continuous and dichotomous measures of hepatic steatosis and fibrosis using multivariable linear and logistic regression.

RESULTS:

In multivariable models adjusting for cardiometabolic risk factors, higher carotid-femoral pulse wave velocity (estimated β per SD, 0.05 [95% CI, 0.01–0.09];
P
=0.003), but not forward pressure wave amplitude and central pulse pressure, was associated with more liver steatosis (higher controlled attenuation parameter). Additionally, higher carotid-femoral pulse wave velocity (β=0.11 [95% CI, 0.07–0.15];
P
<0.001), forward pressure wave amplitude (β=0.05 [95% CI, 0.01–0.09];
P
=0.01), and central pulse pressure (β=0.05 [95% CI, 0.01–0.09];
P
=0.01) were associated with more hepatic fibrosis (higher liver stiffness measurement). Associations were more prominent among men and among participants with obesity, diabetes, and metabolic syndrome (interaction
P
values, <0.001–0.04). Higher carotid-femoral pulse wave velocity, but not forward pressure wave amplitude and central pulse pressure, was associated with higher odds of hepatic steatosis (odds ratio, 1.16 [95% CI, 1.02–1.31];
P
=0.02) and fibrosis (odds ratio, 1.40 [95% CI, 1.19–1.64];
P
<0.001).

CONCLUSIONS:
Elevated aortic stiffness and pressure pulsatility may contribute to hepatic steatosis and fibrosis.
Histidine-Rich Glycoprotein Modulates the Toxic Effects of High-Dose Polyphosphate in Mice
Authors: Malik Rida A. , Zhou Ji , Fredenburgh James C. , Crosby Jeff , Revenko Alexey S. , Healey Jeff S. , Weitz Jeffrey I. 
Published: May 2024

BACKGROUND:
Polyphosphate (polyP), a procoagulant released from platelets, activates coagulation via the contact system and modulates cardiomyocyte viability. High-dose intravenous polyP is lethal in mice, presumably because of thrombosis. Previously, we showed that HRG (histidine-rich glycoprotein) binds polyP and attenuates its procoagulant effects. In this study, we investigated the mechanisms responsible for the lethality of intravenous polyP in mice and the impact of HRG on this process.

METHODS:
The survival of wild-type or HRG-deficient mice given intravenous synthetic or platelet-derived polyP in doses up to 50 mg/kg or saline was compared. To determine the contribution of thrombosis, the effect of FXII (factor XII) knockdown or enoxaparin on polyP-induced fibrin deposition in the lungs was examined. To assess cardiotoxicity, the ECG was continuously monitored, the levels of troponin I and the myocardial band of creatine kinase were quantified, and the viability of a cultured murine cardiomyocyte cell line exposed to polyP in the absence or presence of HRG was determined.

RESULTS:
In HRG-deficient mice, polyP was lethal at 30 mg/kg, whereas it was lethal in wild-type mice at 50 mg/kg. Although FXII knockdown or enoxaparin administration attenuated polyP-induced fibrin deposition in the lungs, neither affected mortality. PolyP induced dose-dependent ECG abnormalities, including heart block and ST-segment changes, and increased the levels of troponin and myocardial band of creatine kinase, effects that were more pronounced in HRG-deficient mice than in wild-type mice and were attenuated when HRG-deficient mice were given supplemental HRG. Consistent with its cardiotoxicity, polyP reduced the viability of cultured cardiomyocytes in a dose-dependent manner, an effect attenuated with supplemental HRG.

CONCLUSIONS:
High-dose intravenous polyP is cardiotoxic in mice, and HRG modulates this effect.
Abstract P456: Expanding a Pipeline to Address San Joaquin Valley Health Inequity and Social Justice
Authors: Siddiqui Maha 
Published: May 2024

Introduction:
San Joaquin Valley (SJV) is the most medically underserved California region. For the last 50 years, SJV continues to face health inequity with not enough physicians for growing communities. With a diverse community of low income and minority groups, the lack of physicians do not represent the workforce of SJV. Many of the talented high school and community college students who aspire to be physicians from SJV leave to bigger cities rather than coming back to enrich their vulnerable communities.

Objectives:
I created and expanded no cost pipeline medical programs (summer programs and online class) for SJV high school students and community college students to increase diversity in the medical profession, encourage underrepresented in medicine (URM) students to pursue medicine and come back to SJV to practice medicine in an effort to lower the patient provider gap.

Methods:
I trained and provided mentorship to medically ambitious low-income high school and community college students in the programs to instill a passion in them to come back after their medical education to practice medicine and lower health equity in SJV. Through the program, students learned about SJV health disparities and applied precision medicine to their own health inequity projects in SJV.

Findings:

-About 76% (106 of 140) of program participants identified as URM
-About 63% (88 of 140) of program participants were first generation
-About 83% (103 of 140) of program participants feel that the pipeline program has helped them solidify their passion in medicine
-About 66% (92 of 140) of program participants aspire to practice medicine in SJV
-About 100% (140 of 140) of program participants feel the program gave them guidance in health disparities, precision medicine, and applying design thinking concepts as a future leader in medicine

Direct Outcomes:

-Students were able to understanding community concerns beyond science and with a health justice perspective
-Served as agents of change by directly communicating with physicians and understanding the need for more URM physicians
-Students received mentorship and confidence to rise as URM first generation college students and pursue STEM majors
-Youth learned the value of service to disadvantaged communities
Disappointing results of popliteal aneurysm endovascular treatment with a new self-expandable covered stent
Authors: Marone Enrico Maria , Brioschi Chiara , Barra Chiara , Rinaldi Luigi Federico 
Published: May 2024

Purpose To describe our clinical experience of endovascular exclusion of popliteal artery aneurysms using the new self-expandable covered stent SOLARIS® (Scitech Medical, Brazil), and to report its results in the context of surgical and endovascular treatment of popliteal artery aneurysms. Case report Among 20 popliteal artery aneurysms undergoing open or endovascular repair in 2022 and 2023, two patients were successfully treated with the Solaris stentgraft. Both patients had a patent popliteal artery and three run-off vessels. After stentgraft implantation, they received dual antiplatelet therapy for three months and they were followed-up with Duplex scan and clinical evaluation after three months, and every six months thereafter. After three months, one Solaris stentgraft had complete thrombosis and the other ruptured, requiring surgical removal. No complications were observed among the other aneurysms treated with open repair or with the Viabahn® stentgraft. Conclusions Endovascular treatment of popliteal aneurysms with the new covered self-expandable stent Solaris resulted in severe complications in the two cases reported, and in worse short-term outcomes than endovascular repair with Viabahn® and open repair. Its off-label use to treat popliteal artery aneurysms should be therefore discouraged.
Modifiable Risk Factors Associated With Cognitive Decline in Late Life Depression: Findings From the Canadian Longitudinal Study on Aging: Facteurs de risque modifiables associés au déclin cognitif dans la dépression en fin de vie : constatations de l'Étude longitudinale canadienne sur le vieillissement
Authors: Wong Melissa , Kiss Alex , Herrmann Nathan , Lanctôt Krista L. , Gallagher Damien 
Published: May 2024

Objective Depression in later life is associated with a two-fold increased risk of dementia. It is not clear to what extent potentially modifiable risk factors account for this association. Method Older adults (age 50 + ) with objective health measures ( n = 14,014) from the Canadian Longitudinal Study on Aging were followed for a mean duration of 35 months. Linear regression analyses were used to determine if clinically significant depression (Centre for Epidemiologic Studies Depression scale score (CESD) ≥ 10) was associated with global cognitive decline, assessed with a neuropsychological battery during follow-up, and if modifiable risk factors mediated this association. Results Depression was associated with an excess of risk factors for cognitive decline including: vascular disease, hypertension, diabetes, apnoea during sleep, higher body mass index, smoking, physical inactivity and lack of social participation. In regression analyses depression remained independently associated with cognitive decline over time (beta −0.060, P = 0.038) as did cerebrovascular disease (beta −0.197, P < 0.001), HbA1C (beta −0.059, P < 0.001), visual impairment (beta −0.070, P = 0.007), hearing impairment (beta −0.098, P < 0.001) and physical inactivity (beta −0.075, P = 0.014). In mediation analyses, we found that cerebrovascular disease ( z = −3.525, P < 0.001), HbA1C ( z = −4.976, P < 0.001) and physical inactivity ( z = −3.998, P < 0.001) partially mediated the association between depression and cognitive decline. Conclusions In this large sample of Canadian older adults incorporating several objective health measures, older adults with depression were at increased risk of cognitive decline and had an excess of potentially modifiable risk factors. Clinicians should pay particular attention to control of diabetes, physical inactivity and risk factors for cerebrovascular disease in older adults presenting with depression as they can contribute to accelerated cognitive decline and may be addressed during routine clinical care.
Research with Black Communities to Inform Co-Development of a Framework for Anti-Racist Health and Community Programming
Authors: Canie Jaimeson , Tobah Selma , Sanchez Anne-Marie , Wathen C. Nadine 
Published: May 2024

Study Background The effects of systemic racism were exacerbated and amplified throughout the COVID-19 pandemic. The resurgence of the “Black Lives Matter” movement in North America brought awareness to the public, especially white people, of the impacts of systemic racism in society and the urgent need for large-scale and institutional anti-racism work. Purpose In collaboration with a local Community Health Centre, this research focused on identifying priority areas for tailored and co-developed anti-Black racism interventions in health services and community programming, as well as examining how purposeful relationships can be created with African, Caribbean, and Black (ACB) communities in London, Ontario. Methods Semi-structured interviews were conducted in either French or English with nine formal or informal leaders from London's ACB communities. Interpretive description methodology guided analysis and interpretation. Results Participants indicated that anti-Black racism is ever-present in the community and in their lives, with systemic racism causing the most harm. Racism should be addressed by creating ACB-specific services, and education for non-Black communities; increased representation, inclusion, and engagement of ACB people within organizations, especially in leadership roles, are essential. A framework based on study findings to guide how organizations can develop authentic and purposeful relationships with ACB communities is presented. Conclusions Organizations will continue to perpetuate systemic racism unless they actively seek to be anti-racist and implement strategies and policies to this end. The proposed framework can guide partnerships between health and community organizations and ACB communities, and support co-development of strategies to address anti-Black racism.
Effects of Tanshinone IIA on Cognitive Impairment in Alzheimer’s Disease Rats Via Oxidative Stress, Inflammatory Responses and Apoptosis
Authors: Ren Wujiang , Li Xiaoxiao , Wang Tingqiao , Liu Yanxia , Dai Xueling , Huo Qing , Wang Shuo , Zheng Qiusheng , Sun Yaxuan 
Published: May 2024

Background The rationale for the pathogenesis of Alzheimer’s disease (AD) is the production of amyloid-beta (Aβ) and its resultant toxic effects. Purpose In this work, rats with AD were used as models to assess the modulatory effects of tanshinone IIA (tan IIA) in alleviating cognitive impairment, oxidative damage, inflammation and apoptosis. Materials and Methods Aβ1–42 was injected bilaterally in the hippocampus to establish an AD rat model. The effects of tan II A on the learning and memory capacities of AD rats were detected by ethological experiments. Tan IIA’s anti-inflammatory and antioxidant capacities were examined in this study using biochemical and immunohistochemical methods on rat hippocampus tissues. Results The experimental data showed that the cognitive ability of rats could be significantly improved by tan IIA. Furthermore, fewer injured neuron apoptosis was demonstrated in the tan IIA rats than in the AD group. More importantly, on the one hand, we discovered that the tan IIA group had considerably lower levels of interleukin 1 beta, tumour necrosis factor-alpha and inducible nitric oxide synthase. On the other hand, tan IIA was discovered to prevent oxidative stress by raising glutathione and superoxide dismutase activity and lowering malondialdehyde, protein carbonyl and 8-hydroxy-2′-deoxyguanosine levels. Conclusion Tan IIA can alleviate cognitive impairment and neuronal cell damage by inhibiting oxidative stress and inflammatory responses during AD.
Tibetan-Origin Edible Chinese Herbal Prescription C18 Protects H9C2 Cardiomyocytes from Cobalt Chloride-induced Hypoxia Injury through the PI3K/AKT Signaling Pathway
Authors: Chang Guoxin , Xie Hongyi , Chen Shu , Wang Ruixue , Zeng Xuxin , Lin Dingmei , Mo Zixuan , Yu Jingjing , Liu Xindan , Zheng Zhaoguang , Wang Yan 
Published: May 2024

Background Altitude sickness is often prone to occur during tourism or work in high-altitude areas. In China, traditional Tibetan medicines have a long history of preventing or treating altitude sickness, especially altitude hypoxia, which may lead to myocardial cell apoptosis and myocardial hypoxia-reoxygenation injury. Purpose This study investigated the effect of a Tibetan-origin edible Chinese herbal prescription (named C18) on protecting H9C2 cardiomyocytes from cobalt chloride-induced hypoxia injury and its potential mechanism. Materials and Methods In this study, a hypoxic injury model of H9C2 cardiomyocytes induced by cobalt chloride was established first. Then the cell viability, relevant antioxidant indicators malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and protein expression (hypoxia-inducible factor 1 alpha (HIF-1α), phosphoinositide 3-kinase (PI3K), phosphorylated protein kinase B (p-AKT)) were measured after pretreatment with or without C18. At last, the specific PI3K/AKT inhibitor LY294002 was applied to verify the antihypoxia signaling pathway. Results C18 could significantly promote normal H9C2 cardiomyocyte proliferation and inhibit apoptosis of hypoxic H9C2 cardiomyocytes, reduce the release of lactate dehydrogenase and MDA, and increase the levels of SOD and GSH-Px antioxidant enzymes. In addition, C18 could significantly downregulate the expression of HIF-1α protein and upregulate the expression of intracellular p-AKT. Moreover, these effects of C18 can be blocked by the specific PI3K/AKT inhibitor LY294002. Conclusion C18 protects H9C2 cardiomyocytes from cobalt chloride-induced hypoxia injury through the PI3K/AKT signaling pathway.
Exploring the Novel Therapeutic Potential of N-acetylcysteine in Depression, Bipolar Disorders and Anxiety
Authors: Syiem Reuben P. , Wahlang Julie B. , R. Krishnamoorthi , Kalyan Pavan B. , Nahakpam Diana , Langstieh Arky Jane 
Published: May 2024

Background Anxiety disorders, bipolar disorder, and depression are prevalent mental health issues that have a substantial impact on both individuals and the community. Many people continue to have symptoms and do not get the right kind of relief from their existing drugs, even after trying conventional therapy methods. Therefore, to enhance the current treatment modalities and patient results, new therapeutic alternatives are required. In recent years, there has been an increase in interest in N-acetylcysteine (NAC) because of its many biological benefits, including its ability to modulate glutamate levels and its antioxidant and anti-inflammatory properties. According to studies, NAC has encouraging anti-depressant properties and may help treat bipolar disease by stabilizing mood and reducing the risk of relapses. Furthermore, through lowering oxidative stress and modifying neurotransmitter networks, NAC has been shown to lessen the symptoms of anxiety. The preclinical and clinical research examining the efficacy of NAC in depression, bipolar disorders, and anxiety are thoroughly analyzed in this review. Methodology Books were reviewed and medical and scientific literature found in MEDLINE and PubMed were analyzed for an assessment of NAC’s therapeutic potential in psychiatric illnesses such as anxiety, depression, and bipolar disorder. Conclusion NAC exhibits potential as a therapeutic agent for psychiatric problems such as anxiety, bipolar disorder, and depression. Performing a thorough clinical study will facilitate proper understanding its efficacy, safety and mechanisms of action.
BRAF-Mutated Melanoma Journey in Latin America: Expert Recommendations From Diagnosis to Treatment
Authors: Bravo-Garzón María A. , Bornstein-Quevedo Leticia , Camargo Veridiana Pires de , Sanku Gayatri , Jansen Angela Marie , Macedo Mariana Petaccia de , Rico-Restrepo Mariana , Chacón Matías 
Published: May 2024

Objectives • Gather a panel of Latin American experts in testing and treating BRAF-melanoma. • Describe the current landscape of BRAF-mutated melanoma in Latin America. • Outline the current gaps in testing and recommend improvements for testing and treating BRAF-mutated melanoma in the region. Introduction Melanoma prevalence in Latin America is lower than in high- and middle-income countries. However, recent data indicate that the region’s incidence and mortality are rising, with more stage IV patients being diagnosed. According to international clinical practice guidelines, conducting BRAF-mutation testing in patients with stage III or stage IV melanoma and high-risk resected disease is imperative. Still, BRAF-mutation testing and targeted therapies are inconsistently available in the region. Methods Americas Health Foundation convened a meeting of Latin American experts on BRAF-mutated melanoma to develop guidelines and recommendations for diagnosis through treatment. Results and Conclusions Some recommendations for improving diagnostics through improving access and reducing the cost of BRAF-mutation testing, enhancing efficiency in pathology laboratories, and creating country-specific local guidelines. The panel also gave treatment recommendations for neo-adjuvant therapy, adjuvant therapy, and therapy for patients with metastatic disease in Latin America.