bluuebunny/crossref_metadata_2025 huggingface dataset:
The poster boys of antiquity’s “capitalism” shunning money? The spread of the alphabet in the Mediterranean as a function of a credit-based, maritime trade
Authors: Pappa Eleftheria
Published: September 2020

Advances into the origins of monetisation in the Mediterranean have shown that even with state-controlled currency circulating, (coinage-less) credit economies existed in parallel, using written documents for transactions, well into the Roman period. The current paper documents that a credit economy facilitated the Phoenician commercial expansion in the Mediterranean (9th-7thc. BCE), becoming the vehicle by which the west Semitic abjad, the Phoenician ‘alphabet’, was rapidly adopted and adapted into various phonetic and syllabic scripts in the Mediterranean. This led to the rapid spread of literacy in societies that had been fully illiterate by then, as the Greeks, or that had never developed literacy. In contrast with previous explanations that saw the spread of literacy in the Mediterranean as a corollary to international trade, the present study postulates that literacy played a functional role within the credit economies that grew with international commerce, thereby providing the impetus for the spread of literacy, providing documentation that substantiates this hypothesis. The study links the rapid spread of literacy to the institutional role of the script within the context of monetised commercial transactions, utilizing archaeological evidence from both ends of the Mediterranean, and interpreting it within its historical context.
Introduction to Proceedings of International Symposium "Migration and Colonization in the Mediterranean during the First Millennium BC"
Authors: Pereira Ronaldo G. Gurgel
Published: September 2020

A comparative approach allowed the debate on different realities of migration and colonization, both in space as in time. Thus, this dossier shall be an interesting asset to those who need to compare bibliographies, sources, usages of concepts and opinions in order to put in perspective their own perceptions of the same phenomenon.
Religion on the move: Mobility, migration and internal religious: Diversity in Biblical and Early Israel and Judah
Authors: Trinka Eric M.
Published: September 2020

Migration is a social process. Religion is fundamentally a social enterprise. Like other aspects of their cultural identities, humans carry their religious identities with them as they traverse geographies. This paper explores the effects of inter-regional movement, as both mobility and migration, on the religious practices and beliefs of ancient Mediterranean peoples, specifically of those who come to be called Israelites. Several studies that account for internal religious differences in Israel and Judah explain Yahweh’s multiple geographic associations as “poly-Yahwism,” assuming that veneration of different geographic associations is in actuality worship directed toward different Yahwehs. Migration studies, specifically those engaging migrant instrumentalization of religion, have not been central conversation partners in these explorations of divine personage. Thus, I argue that the complexities of cultural exchange in the Levantine regions of the Mediterranean in the 1st Millennium BCE and the development of internal religious diversity in ancient Israel can be better understood by integrating modern mobility and migration data. Furthermore, accounting for the dialogical relationship between mobility, migration and religiosity allows scholars to better account for the cultural responses observed in spaces of resettlement and colonization where religion functions both as a source of control and as a resource employed to undermine colonizing power structures. To this end, this paper specifically addresses the occurrence of variant modes of Yahwistic religiosity through two case studies: The first is a migration-informed reading of the Judges 17-18. The second is a mobilities-informed analysis of four inscriptions from Kuntillet ‘Ajrud (Horvat Teman). Together, these explorations provide answers to questions of Yahweh’s multiplicity and his mobile nature.
Migration theory and ‘Greek Colonisation’. Milesians at Naukratis and Abydos
Authors: Knight John Brendan
Published: September 2020

With the application of post-colonial theoretical approaches in the last decades of the twentieth century CE, the study of archaic Greek overseas settlement has arrived at something of a terminological and methodological impasse. Scholars continue to debate whether Mediterranean and Black sea settlement can legitimately be termed ‘colonisation’ yet attempts to modify this language of imperialism have thus far failed to achieve significant alteration of the overarching paradigms. This paper will suggest a new approach to these problems using contemporary migration theory to conceptualise archaic Greek mobility and settlement, through the case studies of Milesian migration to Naukratis in Egypt and Abydos in the Troad during the 7th century BCE. Drawing on aspects of structuration and practice theory, it will seek to describe and explain the multi-faceted structures, practices and agency involved in the migration of Milesian Greeks to these areas. The two chosen case studies will be compared to understand how spatial, social, cultural and political factors may have impacted upon the characteristics of Naukratis and Abydos and the multitude of stimuli surrounding their settlement. This will provide ways to re-envisage an important period of Mediterranean history, offering a flexible methodological approach to be utilised in other contexts.
Beyond the Indigenous/Phoenician divide: Spheres of Interaction and Scales of Integration in the Early Iron Age of Southern Portugal (8th–5th centuries BCE)
Authors: Gomes Francisco João Bentes
Published: September 2020

The arrival of the first Phoenician merchants and colonists in the Iberian Far West tipped off the delicate balance of the regional Late Bronze Age networks, setting in motion a far-ranging process which completely changed the socio-political landscape of Southern Portugal. However, the growing volume of available data seems to show that far from being a linear, straightforward process, the ensuing restructuration was complex and dynamic. In this contribution, it is argued that “traditional” models based on normative views of culture are no longer suited to explain the diversity of the archaeological record, and that new, more nuanced approaches are in order. It is suggested, in particular, that this diversity is the reflection of specific representation discourses in which “traditional” and innovative, often exogenous elements were combined according to variable, situational and socially negotiated identity discourses deployed on multiple levels, from the microregional context of inter- and inter-group interactions to the transregional, Mediterranean level.
A database for the Aegyptiaca from the Iberian SW: Colonial Encounters and the ‘Mediterranization’ of the Atlantic Iberian Societies (8th to 5th centuries BC)
Authors: Pereira Ronaldo G. Gurgel
Published: September 2020

A preliminary study on the aegyptiaca in the Iberian Peninsula. It aims to understand the usages of Egyptian and ‘egyptianised’ material by Phoenicians and natives in the territory. Since such a thematic lacks consistent knowledge, it is interesting to propose new perspectives, by combining the Southwest part of the Peninsula.Thus, this paper aims to deal with the relationship between Phoenician traders and settlers with Celtic-speaking native tribes, throughout the study of material culture. It focuses the regions of Phoenician presence in Spanish Andalusia and Estremadura, plus the Portuguese regions of Algarve, Alentejo and Estremadura. Those regions formed a whole territorial unity – geographical and political – during the transition to Iron Age. Commercial contacts between those following generations of Phoenicians and native peoples (from what is nowadays Portugal) increased the Phoenician influence over the territory – especially the littoral area from the Algarve region to the Tagus estuary.
“I have seen a face with a thousand countenances”: Interpreting Ptolemies' mixed statuary
Authors: Miranda Catarina
Published: September 2020

Around the time the postcolonial paradigm was establishing in the Humanities, so too was the Ptolemaic period receiving growing attention. Scholars studying this chronology, during the second half of the twentieth century, however, understood Egypt’s society and culture as a set of impermeable communities/ traditions, only coexisting with one another. This interpretation caused a radical turn in the historiography of the topic. More significantly, though, it left material culture that did not belong exclusively to neither one of the cultural sets (Greek or Egyptian) largely overlooked, and, later on, underestimated in the debates on who influenced who. The author’s Master dissertation took as a case study the Greco-Egyptian stone sculpture in the round of the male Ptolemaic rulers, looking to further understand the epreviously underestimated objects. They were not underestimated, however, in the sense that their existence was not acknowledged or analysed, but in the sense that the explanation put forward was not complex enough. The authors formulated their interpretation mainly from the point of view of state and elites, disconsidering thus other possible realms of agency. This article presents a part of the investigation, namely the theoretical framework adopted to suggest another interpretation for the existence of the “mixed” statuary of Ptolemaic rulers. Although today Ptolemaic Egypt is not understood as a colonial case, postcolonial studies will contribute to this alternative line of interpretation by decentralizing analysis, from the state to other groups. Nevertheless, the major contribution will come from a theory of consumption, which in turn aims to decentralize studies, from issues of power to other realms.
Brazilian public policy for chronic kidney disease prevention: challenges and perspectives
Authors: Silva Patrícia Aparecida Barbosa , Silva Líliam Barbosa , Santos Joseph Fabiano Guimarães , Soares Sônia Maria
Published: September 2020

Chronic kidney disease is a pathology with exponential increasing prevalence worldwide. This trend derives mainly from population aging and the growth of chronic conditions, making prevention a priority in public health. Thus, this observation instigates debates on the advances and challenges in public policies aimed at facing the progression of this disease and its risk factors in a contemporary reality that requires changes in the management models of chronic conditions. Brazilian and international experiences show that actions to prevent chronic kidney disease in risk groups remain incipient, especially in low-income countries. This area requires investment, supporting planning individualized, interdisciplinary and shared care with primary health care, as well as the user’s responsibility for their care, with proactivity and establishment and monitoring of goals to achieve satisfactory results.
The zero impact of the Vehicle Inspection Program on public health in São Paulo, SP
Authors: Araujo Orlei Ribeiro de , Araujo Milena Corrêa
Published: September 2020

OBJECTIVE: To analyze the impact of two interventions (implementation and suspension of mandatory vehicle inspection) on morbidity and mortality due to conditions related to air pollution, from 2008 to 2017. METHODS: Interrupted time series (ARIMA models), using data available in public repositories. RESULTS: A total of 229,337 children of up to 5 years old were hospitalized due to respiratory diseases, and 1,053 died (average monthly mortality ratio for this population: 1.12/100,000). Exact 137,876 individuals over 40 years old were hospitalized for an acute myocardial infarction, and 19,492 died (3.7/100,000). A total of 11,010 individuals over 40 years old were hospitalized with malignant neoplasms of the respiratory system; 2,898 died (0.5/100,000). A total of 20,807 individuals over 60 years old were hospitalized with chronic obstructive pulmonary diseases; 2,627 died (1.5/100,000). As for strokes, 69,180 individuals were hospitalized, and 10,866 died (2.1/100,000). We found no significant regression coefficient for the implementation or suspension of the program regarding hospitalizations and deaths. 38,207 children of up to 14 years old were hospitalized with asthma, and 25 of them died (0.007/100,000). The coefficients show a monthly increase of 0.05 deaths/100,000 people (p = 0.01) in the post-inspection period. We found no correlation between the measured concentrations of the pollutants PM2.5 and CO – in a monitoring station, in the central region of the municipality – and the implementation or suspension of the inspection. CONCLUSIONS: No evidence confirms that the program had a measurable beneficial impact on morbidity and mortality due to respiratory and circulatory diseases.
Regular use of dental services among university students in southern Brazil
Authors: Echeverria Mariana Silveira , Silva Alexandre Emidio Ribeiro , Agostini Bernardo Antônio , Schuch Helena Silveira , Demarco Flávio Fernando
Published: September 2020

OBJECTIVE: To verify the prevalence and factors associated with regular use of dental services in university students of the Universidade Federal de Pelotas (UFPel). METHODS: This cross-sectional study interviewed 1,865 students aged 18 years or older, starting bachelor’s degrees in 2017, enrolled in the second academic semester of 2017 and in the first of 2018 in classroom courses at UFPel. We considered regular users those who reported regularly going to the dentist with or without perceived dental problems. To test factors associated with regular use of dental services, demographic, socioeconomic and oral health variables were collected. Statistical analyses were based on Poisson regression models. RESULTS: The prevalence of regular use of dental services was 45.0% (95%CI 42.7–47.3). University students of high economic class (PR = 1.47; 95%CI 0.91–2.36), with last private dental appointment (PR = 1.29; 95%CI 1.03–1.61), positive self-perception of oral health (PR = 2.33; 95%CI 1.79–3.03) and no report of toothache in the last six months (PR = 1.22; 95%CI 1.03–1.45) showed higher prevalence of regular use of dental services. CONCLUSION: The results point to inequalities in the regular use of dental services related to socioeconomic factors and a lower use among university students with worse oral health conditions. These results suggest that public health prevention and promotion policies in higher education institutions must be carried out to ensure quality of life among these young adults.
Catheter-Free Arrhythmia Ablation Using Scanned Proton Beams
Authors: Suzuki Atsushi , Deisher Amanda J. , Rettmann Maryam E. , Lehmann H. Immo , Hohmann Stephan , Wang Songyun , Konishi Hiroki , Kruse Jon J. , Cusma Jack T. , Newman Laura K. , Parker Kay D. , Monahan Kristi H. , Herman Michael G. , Packer Douglas L.
Published: September 2020

Background:

Proton beam therapy offers radiophysical properties that are appealing for noninvasive arrhythmia elimination. This study was conducted to use scanned proton beams for ablation of cardiac tissue, investigate electrophysiological outcomes, and characterize the process of lesion formation in a porcine model using particle therapy.

Methods:

Twenty-five animals received scanned proton beam irradiation. ECG-gated computed tomography scans were acquired at end-expiration breath hold. Structures (atrioventricular junction or left ventricular myocardium) and organs at risk were contoured. Doses of 30, 40, and 55 Gy were delivered during expiration to the atrioventricular junction (n=5) and left ventricular myocardium (n=20) of intact animals.

Results:

In this study, procedural success was tracked by pacemaker interrogation in the atrioventricular junction group, time-course magnetic resonance imaging in the left ventricular group, and correlation of lesion outcomes displayed in gross and microscopic pathology. Protein extraction (active caspase-3) was performed to investigate tissue apoptosis. Doses of 40 and 55 Gy caused slowing and interruption of cardiac impulse propagation at the atrioventricular junction. In 40 left ventricular irradiated targets, all lesions were identified on magnetic resonance after 12 weeks, being consistent with outcomes from gross pathology. In the majority of cases, lesion size plateaued between 12 and 16 weeks. Active caspase-3 was seen in lesions 12 and 16 weeks after irradiation but not after 20 weeks.

Conclusions:

Scanned proton beams can be used as a tool for catheter-free ablation, and time-course of tissue apoptosis was consistent with lesion maturation.
Low Plasma Volume and Increased Pressure Load Relate to Concentric Left Ventricular Remodeling After Preeclampsia: A Longitudinal Study
Authors: Breetveld Nicolette M. , Alers Robert‐Jan , Geerts Lauren , van Kuijk Sander M. J. , van Dijk Arie P. , van der Vlugt Maureen J. , Heidema Wieteke M. , van Neer Jolijn , van Empel Vanessa P. M. , Brunner‐La Rocca Hans‐Peter , Scholten Ralph R. , Ghossein‐Doha Chahinda , Spaanderman Marc E. A.
Published: September 2020

Background

During uncomplicated pregnancy, left ventricular remodeling occurs in an eccentric way. In contrast, during preeclamptic gestation, the left ventricle hypertrophies concentrically, concurrent with loss in circulatory volume and increased blood pressure. Concentric cardiac structure persists in a substantial proportion of women and may be associated with pressure and volume load after preeclampsia. We hypothesize that low volume load, as indicated by plasma volume (PV) after preeclampsia and increased pressure load, is associated with remote concentric remodeling.

Methods and Results

In this longitudinal cohort study, we included 100 formerly preeclamptic women. Two visits were performed: at 0.8 years postpartum and at 4.8 years postpartum. During visit 1, we measured blood pressure and PV (I
125
dilution technique, low PV ≤48 mL/kg lean body mass). During the second visit, we assessed cardiac geometry by cardiac ultrasound. Concentric remodeling was defined as relative wall thickness >0.42 and left ventricular mass index ≤95 g/m
2
. We adjusted multivariable analysis for primiparity, systolic blood pressure, PV mL/kg lean body mass, and antihypertensive medication at visit 1. Low PV is associated with remote concentric remodeling (odds ratio [OR], 4.37; 95% CI, 1.06–17.40; and adjusted OR, 4.67; 95% CI, 1.02–21.42). Arterial pressure load (systolic, diastolic, and mean arterial pressure) is also associated with development of concentric remodeling (OR, 1.15 [95% CI, 0.99–1.35]; OR, 1.24 [95% CI, 0.98–1.58]; and OR, 1.20 [95% CI, 0.98–1.47], respectively).

Conclusions

In former preeclamptic women, development toward left ventricular concentric remodeling is associated with low volume load and increased pressure load.
Association of Health Status Scores With Cardiovascular and Limb Outcomes in Patients With Symptomatic Peripheral Artery Disease: Insights From the EUCLID (Examining Use of Ticagrelor in Symptomatic Peripheral Artery Disease) Trial
Authors: Rymer Jennifer A. , Mulder Hillary , Smolderen Kim G. , Hiatt William R. , Conte Michael S. , Berger Jeffrey S. , Norgren Lars , Mahaffey Kenneth W. , Baumgartner Iris , Fowkes F. Gerry , Katona Brian G. , Rockhold Frank , Jones W. Schuyler , Patel Manesh R.
Published: September 2020

Background

There are limited data on health status instruments in patients with peripheral artery disease and cardiovascular and limb events. We evaluated the relationship between health status changes and cardiovascular and limb events.

Methods and Results

In an analysis of the EUCLID (Examining Use of Ticagrelor in Symptomatic Peripheral Artery Disease) trial, we examined the characteristics of 13 801 patients by tertile of health status instrument scores collected in the trial (EuroQol 5‐Dimensions [EQ‐5D], EQ visual analog scale [VAS], and peripheral artery questionnaire). We assessed the association between the baseline health status measurements and major adverse cardiovascular events, major adverse limb events, and lower‐extremity revascularization procedures during trial follow‐up and the association between 12‐month health status change scores and subsequent end points during follow‐up. There were 13 217 (95%) patients with EQ‐5D scores, 13 533 (98%) with VAS scores, and 4431 (32%) with peripheral artery questionnaire scores. Patients in the lowest baseline EQ‐5D tertile (0 to <0.69) were more likely to be female with severe claudication compared with the highest tertile (0.79–1.0;
P
<0.01). Patients in the lowest VAS (0–60) and peripheral artery questionnaire (0–49) tertiles had lower ankle–brachial indices compared with the highest tertiles (80–100 and 76–108, respectively;
P
<0.01). There was a significant association between baseline EQ‐5D, VAS, and peripheral artery questionnaire scores and adjusted major adverse cardiovascular events, major adverse limb events, and lower‐extremity revascularization (
P
<0.05). Improved EQ‐5D and VAS scores over 12 months were associated with reduced risk of subsequent major adverse cardiovascular events or lower‐extremity revascularization (all
P
<0.01).

Conclusions

Although health status instruments are rarely used in clinical practice, these measures are associated with outcomes, including major adverse cardiovascular events, major adverse limb events, and lower‐extremity revascularization. Further research is needed to determine the relationship between changes in these instruments, revascularization, and outcomes.
Blood Pressure and Outcomes in Patients With Different Etiologies of Intracerebral Hemorrhage: A Multicenter Cohort Study
Authors: Zhang Shuting , Wang Zhihao , Zheng Aiping , Yuan Ruozhen , Shu Yang , Zhang Shihong , Lei Peng , Wu Bo , Liu Ming
Published: September 2020

Background

We aimed to investigate the association between blood pressure (BP) and outcomes in intracerebral hemorrhage (ICH) subtypes with different etiologies.

Methods and Results

A total of 5656 in‐hospital patients with spontaneous ICH were included between January 2012 and December 2016 in a prospective multicenter cohort study. Etiological subtypes of ICH were assigned using SMASH‐U (structural lesion, medication, amyloid angiopathy, systemic/other disease, hypertension, undetermined) classification. Elevated systolic BP was defined as ≥140 mm Hg. Hypertension was defined as elevated BP for >1 month before the onset of ICH. The primary outcomes were measured as 1‐month survival rate and 3‐month mortality. A total of 5380 patients with ICH were analyzed, of whom 4052 (75.3%) had elevated systolic BP on admission and 3015 (56.0%) had hypertension. In multinomial analysis of patients who passed away by 3 months, systolic BP on admission was significantly different in cerebral amyloid angiopathy (
P
<0.001), structural lesion (
P
<0.001), and undetermined subtypes (
P
=0.003), compared with the hypertensive angiopathy subtype. Elevated systolic BP was dose‐responsively associated with higher 3‐month mortality in hypertensive angiopathy (
P
trend
=0.013) and undetermined (
P
trend
=0.005) subtypes. In cerebral amyloid angiopathy, hypertension history had significant inverse association with 3‐month mortality (adjusted odds ratio, 0.37, 95% CI, 0.20–0.65;
P
<0.001). Similarly, adjusted Cox regression indicated decreased risk of 1‐month survival rate in the presence of hypertension in patients with cerebral amyloid angiopathy (adjusted hazard ratio, 0.47; 95% CI, 0.24–0.92;
P
=0.027).

Conclusions

This study suggests that the association between BP and ICH outcomes might specifically depend on its subtypes, and cerebral amyloid angiopathy might be pathologically distinctive from the others. Future studies of individualized BP‐lowering strategy are needed to validate our findings.
Population Trends in All‐Cause Mortality and Cause Specific–Death With Incident Atrial Fibrillation
Authors: Singh Sheldon M. , Abdel-Qadir Husam , Pang Andrea , Fang Jiming , Koh Maria , Dorian Paul , Wijeysundera Harindra C. , Ko Dennis T.
Published: September 2020

BACKGROUND

Limited studies have evaluated population‐level temporal trends in mortality and cause of death in patients with contemporary managed atrial fibrillation. This study reports the temporal trends in 1‐year overall and cause‐specific mortality in patients with incident atrial fibrillation.

METHODS AND RESULTS

Patients with incident atrial fibrillation presenting to an emergency department or hospitalized in Ontario, Canada, were identified in population‐level linked administrative databases that included data on vital statistics and cause of death. Temporal trends in 1‐year all‐cause and cause‐specific mortality was determined for individuals identified between April 1, 2007 (fiscal year [FY] 2007) and March 31, 2016 (FY 2015). The study cohort consisted of 110 302 individuals, 69±15 years of age with a median congestive heart failure, hypertension, age (≥75 years), diabetes mellitus, stroke (2 points), vascular disease, age (≥65 years), sex category (female) score of 2.8. There was no significant decline in the adjusted 1‐year all‐cause mortality between the first and last years of the study period (adjusted mortality: FY 2007, 8.0%; FY 2015, 7.8%; P for trend=0.68). Noncardiovascular death accounted for 61% of all deaths; the adjusted 1‐year noncardiovascular mortality rate rose from 4.5% in FY 2007 to 5.2% in FY 2015 (P for trend=0.007). In contrast, the 1‐year cardiovascular mortality rate decreased from 3.5% in FY 2007 to 2.6% in FY 2015 (P for trend=0.01).

CONCLUSIONS

Overall 1‐year all‐cause mortality in individuals with incident atrial fibrillation has not improved despite a significant reduction in the rate of cardiovascular death. These findings highlight the importance of recognizing and managing concomitant noncardiovascular conditions in patients with atrial fibrillation.
Defining the Cardiac Fibroblast Secretome in a Fibrotic Microenvironment
Authors: Ceccato Tova L. , Starbuck Rachel B. , Hall Jessica K. , Walker Cierra J. , Brown Tobin E. , Killgore Jason P. , Anseth Kristi S. , Leinwand Leslie A.
Published: September 2020

Background

Cardiac fibroblasts (CFs) have the ability to sense stiffness changes and respond to biochemical cues to modulate their states as either quiescent or activated myofibroblasts. Given the potential for secretion of bioactive molecules to modulate the cardiac microenvironment, we sought to determine how the CF secretome changes with matrix stiffness and biochemical cues and how this affects cardiac myocytes via paracrine signaling.

Methods and Results

Myofibroblast activation was modulated in vitro by combining stiffness cues with TGFβ1 (transforming growth factor β 1) treatment using engineered poly (ethylene glycol) hydrogels, and in vivo with isoproterenol treatment. Stiffness, TGFβ1, and isoproterenol treatment increased AKT (protein kinase B) phosphorylation, indicating that this pathway may be central to myofibroblast activation regardless of the treatment. Although activation of AKT was shared, different activating cues had distinct effects on downstream cytokine secretion, indicating that not all activated myofibroblasts share the same secretome. To test the effect of cytokines present in the CF secretome on paracrine signaling, neonatal rat ventricular cardiomyocytes were treated with CF conditioned media. Conditioned media from myofibroblasts cultured on stiff substrates and activated by TGFβ1 caused hypertrophy, and one of the cytokines in that media was insulin growth factor 1, which is a known mediator of cardiac myocyte hypertrophy.

Conclusions

Culturing CFs on stiff substrates, treating with TGFβ1, and in vivo treatment with isoproterenol all caused myofibroblast activation. Each cue had distinct effects on the secretome or genes encoding the secretome, but only the secretome of activated myofibroblasts on stiff substrates treated with TGFβ1 caused myocyte hypertrophy, most likely through insulin growth factor 1.
Financial Toxicity in Atherosclerotic Cardiovascular Disease in the United States: Current State and Future Directions
Authors: Khera Rohan , Valero-Elizondo Javier , Nasir Khurram
Published: September 2020

Atherosclerotic cardiovascular disease (ASCVD) has posed an increasing burden on Americans and the United States healthcare system for decades. In addition, ASCVD has had a substantial economic impact, with national expenditures for ASCVD projected to increase by over 2.5‐fold from 2015 to 2035. This rapid increase in costs associated with health care for ASCVD has consequences for payers, healthcare providers, and patients. The issues to patients are particularly relevant in recent years, with a growing trend of shifting costs of treatment expenses to patients in various forms, such as high deductibles, copays, and coinsurance. Therefore, the issue of
“
financial toxicity” of health care is gaining significant attention. The term encapsulates the deleterious impact of healthcare expenditures for patients. This includes the economic burden posed by healthcare costs, but also the unintended consequences it creates in form of barriers to necessary medical care, quality of life as well tradeoffs related to non‐health–related necessities. While the societal impact of rising costs related to ASCVD management have been actively studied and debated in policy circles, there is lack of a comprehensive assessment of the current literature on the financial impact of cost sharing for ASCVD patients and their families. In this review we systematically describe the scope and domains of financial toxicity, the instruments that measure various facets of healthcare‐related financial toxicity, and accentuating factors and consequences on patient health and well‐being. We further identify avenues and potential solutions for clinicians to apply in medical practice to mitigate the burden and consequences of out‐of‐pocket costs for ASCVD patients and their families.
Toward a Unified Framework for Cognitive Maps
Authors: Kim Woori , Yoo Yongseok
Published: September 2020

In this study, we integrated neural encoding and decoding into a unified framework for spatial information processing in the brain. Specifically, the neural representations of self-location in the hippocampus (HPC) and entorhinal cortex (EC) play crucial roles in spatial navigation. Intriguingly, these neural representations in these neighboring brain areas show stark differences. Whereas the place cells in the HPC fire as a unimodal function of spatial location, the grid cells in the EC show periodic tuning curves with different periods for different subpopulations (called modules). By combining an encoding model for this modular neural representation and a realistic decoding model based on belief propagation, we investigated the manner in which self-location is encoded by neurons in the EC and then decoded by downstream neurons in the HPC. Through the results of numerical simulations, we first show the positive synergy effects of the modular structure in the EC. The modular structure introduces more coupling between heterogeneous modules with different periodicities, which provides increased error-correcting capabilities. This is also demonstrated through a comparison of the beliefs produced for decoding two- and four-module codes. Whereas the former resulted in a complete decoding failure, the latter correctly recovered the self-location even from the same inputs. Further analysis of belief propagation during decoding revealed complex dynamics in information updates due to interactions among multiple modules having diverse scales. Therefore, the proposed unified framework allows one to investigate the overall flow of spatial information, closing the loop of encoding and decoding self-location in the brain.
High Performance Molecular Detection Biosensor Using Plasmonic Spiral Nanoantenna Based on Optical Fiber
Authors: Elrashidi Ali
Published: September 2020

Biomedical sensor that sense different molecules with a high refractive index sensitivity is proposed in this work. Plasmonic nanospiral antenna is mounted on a top surface of an optical fiber to reflect the incident optical signal back to the fiber. The reflected signal depends on
the nanospiral antenna material, dimensions and the surrounding medium. Using streptavidin molecule, the nanospiral antenna have been simulated based on finite difference time domain method to optimize its dimensions. The optimum dimensions are 10 nm, 55 nm and 40 nm for inner-outer thicknesses
and height respectively. The introduced biosensor can detect different molecules based on surface plasmonic resonance, which depends on the shifting of the peak wavelength according to the molecules type. The detected molecules are Streptavidin, Urease, Uricase molecules and Glucose oxidase
and Cholesterol oxidase enzymes with a high sensitivity. The maximum refractive index sensitivity is obtained when sensing cholesterol oxidase molecules with 3028 nm/RIU at 3.58 μm peak wavelength. Figure of merit and quality factor are also calculated for all detected molecules.
Finally, electric field and optical power, before and after binding, of the reflected signal are illustrated and discussed.
Polyelectrolyte Membrane with Hydroxyapatite and Silver Nanoparticles as a Material for Modern Wound Dressings
Authors: Antosiak-Iwańska Magdalena , Bącal Paweł , Kazimierczak Beata , Kwiatkowska Angelika , Godlewska Ewa , Grzeczkowicz Anna , Stachowiak Radosław , Bielecki Jacek , Granicka Ludomira
Published: September 2020

Modern wound dressings not only play a covering role but also facilitate the function of the wound, contributing to a faster healing process. In this paper, we present a polyelectrolyte system with nanosized elements that could stimulate the growth of eukaryotic cells while providing
antimicrobial properties, which may be recommended as a potential dressing material. The proposed platform consisted of polyethyleneimine, hydroxyapatite, and silver nanoparticles and was characterized using various macroscopic techniques. The constructed membrane scaffold was evaluated with
immobilized WEHI 164 cells as a model system for cells sustained at the interface of bone and skin. Moreover, the bacteriostatic function of the designed membrane material was evaluated using different bacterial strains.
Hollow NiAl(OH)x Nanocapsules to Enable Effective Glucose Oxidase Delivery and Synergistic Therapy
Authors: Liu Bin , Chu Qiang , Liao Linhua , Wu Yongjun , Di Silvio Lucy , Li Xiang , Han Gaorong
Published: September 2020

Cellular starvation induced by glucose oxidase (GOx) had been extensively explored as a potential approach for tumor therapy. However, the therapeutic efficacy suffers daunting challenges due to the unsatisfactory intracellular transportation of GOx molecules. Herein for the first time,
hydroxide nanoparticles with unique hollow microstructure (denoted as H-NiAl(OH)x) were designed and synthesized for GOx delivery. In this system, despite its intrinsic degradation properties in acidic tumor microenvironment, Ni2+ ions released during degradation
may catalyze a Fenton reaction to induce considerable production of cytotoxic hydroxyl radicals (OH). The cavity of hollow nanocapsules provides large surface area, and favors GOx capsulation and delivery. The findings indicate the intracellular glucose can be effectively consumed by GOx transported,
and the reaction products consisting of acid and H2O2 facilitate the OH induction of nanocapsules in a synergistic manner. Both in vitro and in vivo antitumor properties have been consequently achieved by H-NiAl(OH)x/GOx systems. This study
offering catalytic nanocapsules based on Ni2+ ions may spark a series of follow-on explorations in constructing drug delivery and therapeutic systems for synergistic tumor treatment.
MRI-Guided Focused Ultrasound-Induced Blood Brain Barrier Disruption to Deliver Glial Cell Line Derived Neurotropic Factor Proteins into Brain to Treat Rat Depression
Authors: Wang Feng , Li Nana , Wei Xixi , Jia Xiaojian , Liu Huanhuan , Wang Yongling , Shi Yu , Pan Min , Wang Yue , Yin Yaling , Yan Fei , Chen Yun
Published: September 2020

Glial cell line derived neurotropic factor (GDNF) plays a crucial role in the development and maintenance of glial cells, serotonergic and dopaminergic neurons. A positively therapeutic effect has been demonstrated on some animal neurodegenerative diseases. However, the inability to
deliver the protein across blood brain barrier (BBB) into damaged brain region limits its clinical application. Here, we developed GDNF-loaded microbubbles (MBs) and achieved a local and precise delivery of GDNF into the brain through MRI-guided focused ultrasound-induced BBB disruption. To
demonstrate the therapeutic effect, rat depression model was developed by chronic mild stress treatment. Typical depression behaviors were confirmed. MRI-guided focused ultrasound was used to irradiate the GDNF-loaded MBs. Obvious BBB opening was observed in the treated rat brains and a significant
higher GDNF concentration was detected in the ultrasound-treated brain tissues. Behavioral tests demonstrated the increased GDNF could reverse the depressive-like behaviors induced by chronic mild stress, improve the expression of 5-HT 1B receptor and the protein p11, and increase the number
of 5-HT or TPH2 immunoreactive neurons. In conclusion, our study provided an effective approach to deliver GDNF proteins into brain to treat rat depression through MRI-guided focused ultrasound-induced destruction of blood-brain barrier.
Near-Infrared Responsive Doxorubicin Loaded Hollow Mesoporous Prussian Blue Nanoparticles Combined with Dissolvable Hyaluronic Acid Microneedle System for Human Oral Squamous Cell Carcinoma Therapy
Authors: Xu Yuntao , Hao Ying , Li Wei , Xiao Yao , Zhou Tianlin , Hu Danrong , Liu Qingya , Zhou Xingli , Qian Zhiyong
Published: September 2020

Oral squamous cell carcinoma (OSCC) is one of the most common cancers in developing countries particularly in those aged over 50. Traditional treatment is with surgery, radiotherapy, chemotherapy, or a combination of these which often results in considerable discomfort to the patient.
Here we describe a potential alternative which employs a near-infrared (NIR) responsive dissolvable microneedle system (HMPBs&DOX@HA MNs) made of hyaluronic acid (HA) with hollow mesoporous Prussian blue nanoparticles (HMPBs) loaded with doxorubicin (DOX). HMPBs&DOX@HA MNs can easily
penetrate the skin, and shows the ability to heat and maintain the internal temperature of tumor tissue at more than 60 C under the irradiation of an NIR laser. Besides, the DOX release behavior can also be regulated by the NIR laser. HMPBs&DOX@HA MNs reveals not only strong cell inhibition
in vitro, but also prominent antitumor efficacy in vivo with all tumor-bearing mice cured in just one treatment and with no recurrence. This innovative transdermal drug delivery system minimizes the side effects while eliminating tumors. It has great potential to be an effective
clinical treatment of OSCC.
Hollow Mesoporous Silica Nanoparticles Loaded with Eugenol for Regulating the Central Nervous System
Authors: Wang Jianze , Lu Zhiguo , Shen Jie , Peng Huan , Zhang Tianlu , Niu Yunwei , Xiao Zuobing , Hao Jifu , Zhang Xin
Published: September 2020

Fragrances are extensively applied in food, daily chemicals, tobacco and medicine industries. However, too strong volatility of fragrances results in a fast release rate, thereby reducing the usage time of aromatherapy products. Although loading fragrances into nanomaterials is capable
of slowing their rates of release, the encapsulation efficiency of traditional nanomaterials is very low, and the nanomaterials themselves are not stable. Herein, hollow mesoporous silica nanoparticles (hMSNs) were designed for encapsulation of eugenol and the nano-fragrance was named EG@hMSNs.
The structure of hMSNs was stable and the encapsulation rate of eugenol reached 46.5%. Besides, EG@hMSNs could significantly slow the release rate of eugenol. Subsequently, the EG@hMSNs were testified that they had positive roles in stress relief by open field tests. The molecular mechanisms
of these positive effects on the central nervous system were then explored. Furthermore, the preparation method of hMSCs was simple, and the preparation cost was low. Therefore, EG@hMSNs are expected to be industrially produced and have a great application prospect.
A Collagen Fiber Membrane Aided Chondroprotective-Based Strategy for Enhancing Integration of Regenerative Neo-Cartilage
Authors: Yang Wenyu , Wang Ziqiang , Du Fuchong , Cao Yiting , Du Bo , Shi Yanping , Zhang Qiqing , Li Xuemin
Published: September 2020

The lack of neo-cartilage integration with host tissues is a great challenge for the clinical translation of new technologies for the repair of articular cartilage (AC) defect. Recently, we developed a promising double-layered collagen-based system for targeted delivery of fibroblast
growth factor 2 (FGF2) to the subchondral bone for AC repair. The system effectively promoted the regeneration of both cartilage and subchondral bone. However, neo-cartilage integration was unsatisfactory, which might be due to the presence of a zone of cell death (ZCD) in the cartilage induced
by injury. Here, we hypothesized that maintaining cell viability in the region surrounding the defect and decreasing the size of ZCD by using chondroprotective agents such as insulin-like growth factor-1 (IGF-1), might be an effective strategy to improve neo-cartilage integration. A targeted
delivery system for IGF-1 to cartilage based on the FGF2 delivery system was formulated to weaken the impact on the effects of FGF2. The two growth factors were incorporated into the different layers of the membrane without interdiffusion. Due to the different densities of collagen fibers
in the different layers, the in vitro and in vivo assays demonstrated that both proteins were released via unidirectional diffusion without mixing or lateral diffusion. Particularly, the released IGF-1 increased the viability of chondrocytes, decreased the ZCD size, and enhanced
the integration of regenerative neo-cartilage with host tissues, without any undesirable effects on the FGF2mediated regeneration of cartilage and subchondral bone. Taken together, our findings demonstrate that the collagen fiber membrane-aided chondroprotective-based strategy is an effective
way to improve neo-cartilage integration.
Liver Inflammation and Fibrosis Induced by Long-Term Exposure to Nano Titanium Dioxide (TiO2) Nanoparticles in Mice and Its Molecular Mechanism
Authors: Hong Fashui , Ji Jianhui , Ze Xiao , Zhou Yingjun , Ze Yuguan
Published: September 2020

Titanium dioxide (TiO2) and nano-sized titanium dioxide (nano-TiO2), which are used in food production, may be harmful to the body. Long-term exposure to nano-TiO2 can lead to hepatic injury; however, the effect of nano-TiO2 on liver fibrosis
and the underlying mechanism remain unclear. The TGF-β/Smad/MAPK/Wnt signaling pathway is important for tissue fibrosis. In this study, mice were fed nano-TiO2 (2.5, 5, and 10 mg/kg body weight) for nine consecutive months to investigate its effect on liver fibrosis.
Nano-TiO2 induced hepatic inflammatory cell infiltration and hepatic fibrosis and upregulated the expression of HIF-1α (+75-fold to +2.38-fold), Wnt3 (+12% to +135%), Wnt4 (1.33-fold to 6-fold), NF-κB (+3.13% to +34.38%), TGF-β1 (+1307-fold
to +1.85-fold), TGF-β1R (+0.8-fold to 1.33-fold), Smad-2 (+0.58-fold to +1.58-fold), ILK (+0.43-fold to +1.19-fold), ECM (+1.82-fold to 2.36-fold), calpain 2 (+0.11-fold to +0.78-fold), α-SMA (+0.63-fold to +1.56-fold), c-Myc (+0.27-fold to +0.46-fold), and collagen
I (+8% to +36%), and increased the phosphorylation level of p38MAPK (+66.67% to +153.33%) in inflammatory and fibrotic liver tissues, whereas it downregulated cyclin D (–6.25% to –43.75%) and decreased the phosphorylation levels of GSK-3β (–3.12% to –46.88%)
and β-catenin (–19.57% to –45.65%). These results indicate that hepatic fibrosis induced by nano-TiO2 is mediated by the TGF-β/Smads/MAPK/Wnt signaling pathway. This study provides insight into the mechanism underlying hepatic toxicity induced
by nano-TiO2 .
The Mitochondrial-Targeted Peptide, SS31, Protects Murine 661W Cells from Oxidative Damage via Induction of Autophagy
Authors: He Yuan , He Beilei , Zhang Ruixue , Quan Zhuoya , Xu Yun , Chen Zejun , Ren Yuan
Published: September 2020

The goal of this study was to examine the impact of the mitochondrial-targeted antioxidant peptide, SS31, and its role in promoting autophagy in cone photoreceptor 661W cells that were subjected to oxidative damage. To do so, we examined the viability of 661W cells in the presence of
increasing concentrations of H2O2 with or without SS31 pre-treatment using the MTT assay and by expression of autophagy and apoptosis-associated proteins LC3-II/I, P62, and caspase-3. Autophagy was evaluated by fluorescence microscopy in cells stained with monodansyl
cadaverine (MDC). Autophagy was induced with rapamycin (Rap) and inhibited with bafamycin A1 (bafA1) followed by examination of Reactive oxygen species (ROS) levels in target 661W cells by fluorescence microscopy and flow cytometry. Annexin V/PI staining was used to evaluate the rate of apoptosis
and mRNA sequencing (mRNA-seq) analysis (Illumina platform) was performed on H2O2-exposed 661W cells treated with SS31. Among our results, we observed a substantial and concentration-dependent decrease in 661W cell viability in response to H2O2-exposure;
production of ROS, autophagy and apoptosis were induced at 8 h in response to exposure to 100 μM of H2O2. Pre-treatment with 100 nM SS31 resulted in significant attenuation of H2O2-mediated cytotoxicity, together with reduced ROS production
and enhanced autophagy observed in response to oxidative stress. Both Rap and bafA1 were used to modulate SS31-mediated autophagy; the impact of Rap was similar to that of SS31. By contrast, administration of bafA1 counteracted autophagy induced by SS31. Furthermore, mRNAseq analysis revealed
that SS31 promoted significant alterations in gene expression in 661W cells and suggested that autophagy was induced via the mTORC1-mediated signaling. In conclusion, our results indicate that exposure to H2O2 resulted in reduced 661W cell viability via mechanisms associated
with oxidative damage, apoptosis, and autophagy. Notably, we demonstrated that pre-treatment with SS31 protects 661W cells from H2O2-induced oxidative damage that may result in part from induction of autophagy via mTORC1-mediated signaling pathways.