bluuebunny/crossref_metadata_2025 huggingface dataset:
Examining the Drivers of Racial/Ethnic Disparities in Non-Adherence to Antihypertensive Medications and Mortality Due to Heart Disease and Stroke: A County-Level Analysis
Authors: Donneyong Macarius M. , Fischer Michael A. , Langston Michael A. , Joseph Joshua J. , Juarez Paul D. , Zhang Ping , Kline David M.
Published: December 2021

Background: Prior research has identified disparities in anti-hypertensive medication (AHM) non-adherence between Black/African Americans (BAAs) and non-Hispanic Whites (nHWs) but the role of determinants of health in these gaps is unclear. Non-adherence to AHM may be associated with increased mortality (due to heart disease and stroke) and the extent to which such associations are modified by contextual determinants of health may inform future interventions. Methods: We linked the Centers for Disease Control and Prevention (CDC) Atlas of Heart Disease and Stroke (2014–2016) and the 2016 County Health Ranking (CHR) dataset to investigate the associations between AHM non-adherence, mortality, and determinants of health. A proportion of days covered (PDC) with AHM < 80%, was considered as non-adherence. We computed the prevalence rate ratio (PRR)—the ratio of the prevalence among BAAs to that among nHWs—as an index of BAA–nHW disparity. Hierarchical linear models (HLM) were used to assess the role of four pre-defined determinants of health domains—health behaviors, clinical care, social and economic and physical environment—as contributors to BAA–nHW disparities in AHM non-adherence. A Bayesian paradigm framework was used to quantify the associations between AHM non-adherence and mortality (heart disease and stroke) and to assess whether the determinants of health factors moderated these associations. Results: Overall, BAAs were significantly more likely to be non-adherent: PRR = 1.37, 95% Confidence Interval (CI):1.36, 1.37. The four county-level constructs of determinants of health accounted for 24% of the BAA-nHW variation in AHM non-adherence. The clinical care (β = −0.21, p < 0.001) and social and economic (β = −0.11, p < 0.01) domains were significantly inversely associated with the observed BAA–nHW disparity. AHM non-adherence was associated with both heart disease and stroke mortality among both BAAs and nHWs. We observed that the determinants of health, specifically clinical care and physical environment domains, moderated the effects of AHM non-adherence on heart disease mortality among BAAs but not among nHWs. For the AHM non-adherence-stroke mortality association, the determinants of health did not moderate this association among BAAs; the social and economic domain did moderate this association among nHWs. Conclusions: The socioeconomic, clinical care and physical environmental attributes of the places that patients live are significant contributors to BAA–nHW disparities in AHM non-adherence and mortality due to heart diseases and stroke.
“They Wait until the Disease Has Taking over You and the Doctors Cannot Do Anything about It”: Qualitative Insights from Harambee! 2.0
Authors: Hassan Shukri A. , Mohamed Farah , Sheikh Najma , Basualdo Guiomar , Daniel Nahom A. , Schwartz Rahel , Gebreselassie Beyene Tewelde , Beyene Yikealo K. , Gabreselassie Luwam , Bayru Kifleyesus , Tadesse Bethel , Libneh Hirut Amsalu , Shidane Mohamed , Benalfew Sophia , Ali Ahmed , Rao Deepa , Patel Rena C. , Kerani Roxanne P.
Published: December 2021

African immigrants make up a large subgroup of Black/African-Americans in the US. However, because African immigrant groups are typically categorized as “Black,” little is known about their preventative healthcare needs. Differences in culture, life and healthcare experiences between African immigrant populations and US-born people may influence preventive health care uptake. Thus, policymakers and healthcare providers lack information needed to make informed decisions around preventive care for African immigrants. This formative study was conducted among the largest East African immigrant communities in King County, WA. We recruited religious leaders, community leaders, health professionals, and lay community members to participate in thirty key informant interviews and five focus group discussions (n = 72 total), to better understand preventative healthcare attitudes in these communities. Through inductive coding and thematic analysis, we identified factors that impact preventative healthcare attitudes of the Somali, Ethiopian and Eritrean immigrant communities and deter them from accessing and utilizing healthcare. Cultural beliefs and attitudes around preventative healthcare, mistrust of westernized healthcare, religious beliefs/views, intersecting identities and shared immigrant experiences all influence how participants view preventative healthcare. Our results suggest that interventions that address these factors are needed to most effectively increase uptake of preventative healthcare in African immigrant communities.
Spatio-Temporal Effects of Multi-Dimensional Urbanization on Carbon Emission Efficiency: Analysis Based on Panel Data of 283 Cities in China
Authors: Zhou Zhanhang , Cao Linjian , Zhao Kuokuo , Li Dongliang , Ding Ci
Published: December 2021

Under the influence of complex urbanization, improving the carbon emission efficiency (CEE) plays an important role in the construction of low-carbon cities in China. Based on the panel data of 283 prefectural-level cities in China from 2005 to 2017, this study evaluated the CEE by the US-SBM model, and explored the spatial agglomeration evolution characteristics of CEE from static and dynamic perspectives by integrating ESDA and Spatial Markov Chains. Then, the spatial heterogeneity of the impacts of multi-dimensional urbanization on CEE were analyzed by using the Geographically and Temporally Weighted Regression (GTWR). The results show that: (1) with the evolution of time, the CEE has a trend of gradual improvement, but the average is 0.4693; (2) from the perspective of spatial static agglomeration, the “hot spots” of CEE mainly concentrated in Shandong Peninsula, Pearl River Delta, and Chengdu-Chongqing urban agglomeration; The dynamic evolution of CEE gradually forms the phenomenon of “club convergence”; (3) urbanization of different dimensions shows spatial heterogeneity to CEE. The impact of economic urbanization in northern cities on CEE shows an inverted “U” shape, and the negative impact of spatial urbanization on CEE appears in the northwest and resource-based cities around Bohai Sea. Population and social urbanization have a positive promoting effect on CEE after 2010. These findings may help China to improve the level of CEE at the city level and provide a reference for low-carbon decision-making.
Analysis of Cameroon’s Sectoral Policies on Physical Activity for Noncommunicable Disease Prevention
Authors: Tatah Lambed , Mapa-Tassou Clarisse , Shung-King Maylene , Oni Tolu , Woodcock James , Weimann Amy , McCreedy Nicole , Muzenda Trish , Govia Ishtar , Mbanya Jean Claude , Assah Felix
Published: December 2021

Physical inactivity is increasing in low- and middle-income countries (LMICs), where noncommunicable diseases (NCDs), urbanisation and sedentary living are rapidly growing in tandem. Increasing active living requires the participation of multiple sectors, yet it is unclear whether physical activity (PA)-relevant sectors in LMICs are prioritising PA. We investigated to what extent sectors that influence PA explicitly integrate it in their policies in an LMIC such as Cameroon. We systematically identified policy documents relevant to PA and NCD prevention in Cameroon; and using the Walt and Gilson policy triangle we described, analysed, and interpreted the policy contexts, contents, processes, and actors. We found 17 PA and NCD policy documents spanning from 1974 to 2019 across seven ministries. Thirteen (13/17) policies targeted infrastructure improvement, and four (4/17) targeted communication for behaviour change, all aiming to enhance leisure domain PA. Only the health sector explicitly acknowledged the role of PA in NCD prevention. Notably, no policy from the transport sector mentioned PA. Our findings highlight the need for intersectoral action to integrate PA into policies in all relevant sectors. These actions will need to encompass the breadth of PA domains, including transport, while emphasising the multiple health benefits of PA for the population.
Effect of Caregivers’ Parenting Styles on the Emotional and Behavioral Problems of Left-Behind Children: The Parallel Mediating Role of Self-Control
Authors: Pan Weigang , Gao Baixue , Long Yihong , Teng Yue , Yue Tong
Published: December 2021

Childhood is an important period of individual psychological development, and parents’ company and parenting styles are highly significant to children’s personality cultivation and mental health. With the advancement of China’s modernization and urbanization, left-behind children without their parents’ company have become a growing concern. Compared with children raised by their parents, left-behind children are more likely to show social maladaptation and mental health problems. This study explored the mediating effects of left-behind children’s dual mode of self-control between caregivers’ parenting styles and emotional and behavioral problems (EBPs). In this study, 469 left-behind children in senior classes of primary schools were investigated by adopting the caregivers’ parenting styles questionnaire of left-behind children, the dual-mode of self-control scale and the strengths and difficulties questionnaire. This study found that (1) the protective and risk factors for caregivers’ parenting styles not only directly affected EBP, but also affected it through the mediating effect of the dual-mode of self-control, and (2) the mediating effect of the impulsive system was significantly greater than that of the control system. This study confirmed that caregivers’ parenting styles had an important impact on left-behind children’s psychological growth: positive parenting styles not only directly reduced the risk of EBP, but also indirectly improved left-behind children’s mental health by promoting their level of self-control; negative parenting styles directly increased the risk of EBP and indirectly affected left-behind children’s mental problems by enhancing their level of impulsiveness. These findings provide an important basis for reducing the risk of mental health problems and cultivating good personality qualities of left-behind children.
Italian Validation of the Scale of Psychological Abuse in Intimate Partner Violence (EAPA-P)
Authors: Lausi Giulia , Barchielli Benedetta , Burrai Jessica , Giannini Anna Maria , Cricenti Clarissa
Published: December 2021

Psychological and emotional forms of violence often represent a danger alarm and an important risk factor for other forms of intimate partner violence (IPV). Measuring psychological violence raises several issues of conceptualization and definition, which lead to the development of several assessment instruments; among them, the Scale of Psychological Abuse in Intimate Partner Violence (EAPA-P) showed good psychometric proprieties in a Spanish population and is used to identify which strategies are acted out to engage in psychological violence. The aim of the present study was to investigate the psychometric properties of the Italian version of EAPA-P among a group of Italian-speaking women (N = 343), thus evaluating its psychometric characteristics. Based on the English translation of the original Spanish version, an 11-item form of the EAPA-P was obtained, validity has been assessed through measures of emotion dysregulation, interpersonal guilt, conflict among partners and depression, anxiety, and stress symptomatology. Moreover, differences among groups were conducted to identify the capacity of the Italian version of EAPA-P to discriminate among women reporting experiencing psychological violence (N = 179), and who don’t (N = 150). Results showed an excellent internal validity, good correlations, and a good discriminatory ability of the scale. Strengths, limitations, and practical implications of the study have been discussed according to recent literature.
Social Capital during the First Wave of the COVID-19 Outbreak: The Case of the Island of Menorca
Authors: Villalonga-Olives Ester , Kawachi Ichiro , Hernández-Aguado Ildefonso
Published: December 2021

The rapidly evolving coronavirus pandemic has drastically altered the economic and social lives of people throughout the world. Our overall goal is to understand the mechanisms through which social capital shaped the community response to the pandemic on the island of Menorca, Spain, which was under a strict lockdown in 2020. Between April and June 2020, we performed qualitative interviews (n = 25) of permanent residents of the island. From the findings, it is evident that social capital is an important resource with the capacity to organize help and support. However, the dark sides of social capital, with lack of social cohesion and lack of trust, also emerged as an important negative issue. We identified sources of tension that were not resolved, as well as important sociodemographic differences that are primary drivers for health inequalities. The investment in social networks and social capital is a long-term need that should consider sociodemographic vulnerability.
Psychometric Properties of the Multidimensional Temperance Scale in Adolescents
Authors: García-Vázquez Fernanda Inéz , Valdés-Cuervo Angel Alberto , Navarro-Villarreal Alma Georgina , Parra-Pérez Lizeth Guadalupe , Durón-Ramos Maria Fernanda , Fimbres-Celaya Daniela
Published: December 2021

Recent research has shown the relevance of measuring the virtue of temperance. The present study tested a multidimensional and second-order structure scale to assess temperance using a sub-scale of the Values in Action Inventory of Strengths for Youth (VIA-Youth). Scale properties were tested using data from a sample of 860 adolescents aged from 12 to 18 years old (M = 14.28 years, SD = 1.65). The sample was randomly split into two subsamples for model cross-validation. Using the first sample, we assessed scale dimensionality, measurement invariance, and discriminant and concurrent validity. A second sample was used for model cross-validation. Confirmatory factorial analysis confirmed the fit of one second-order factor temperance virtue model, with the dimensions of forgiveness, modesty, prudence, and self-control. The results indicate scale measurement equivalence across gender and stage of adolescence (early vs. middle). Latent means difference tests showed significant differences in forgiveness, modesty, and self-regulation by gender, and modesty according to adolescence stage. Moreover, the scale showed discriminant and concurrent validity. These findings indicate that this scale is helpful for assessing temperance in adolescents and suggest the value of temperance as a multidimensional and second-order construct.
Environmental Performance in EU Countries from the Perspective of Its Relation to Human and Economic Wellbeing
Authors: Ulman Simona-Roxana , Mihai Costica , Cautisanu Cristina , Brumă Ioan-Sebastian , Coca Oana , Stefan Gavril
Published: December 2021

The actual development challenges impose new criteria of national performance evaluation, the concept of wellbeing tending to be measured not just in terms of economic and social dimensions, but also vs. the environment. Accordingly, considering the national environmental performance among the EU countries in 2006–2019 period, we grouped them and concentrated on the clusters registering the highest and lowest levels, analyzing how the components of the human and economic dimensions influence it. Applying panel data models, our main results emphasized that, firstly, for the countries with a better environmental performance, sufficient drinking water, safe sanitation, education, gender equality, and good governance were significant; in the countries with the lowest levels of environmental wellbeing, sufficient food, sufficient to drink, education, and income distribution were insignificant, while the remaining components were relevant. Secondly, in both groups of countries, organic farming and public debt were significant; nevertheless, differences were observed for genuine savings and employment, for which the peculiarities of economic activities seemed to be materialized as different influences upon environmental wellbeing. Our study draws alarm signals regarding the development patterns applied in the EU, seeming to have results that strengthen the sustainable goals, but not sufficient for exceeding the traditional growth-oriented model.
Gait Assessment Using Wearable Sensor-Based Devices in People Living with Dementia: A Systematic Review
Authors: Weizman Yehuda , Tirosh Oren , Beh Jeanie , Fuss Franz Konstantin , Pedell Sonja
Published: December 2021

The ability of people living with dementia to walk independently is a key contributor to their overall well-being and autonomy. For this reason, understanding the relationship between dementia and gait is significant. With rapidly emerging developments in technology, wearable devices offer a portable and affordable alternative for healthcare experts to objectively estimate kinematic parameters with great accuracy. This systematic review aims to provide an updated overview and explore the opportunities in the current research on wearable sensors for gait analysis in adults over 60 living with dementia. A systematic search was conducted in the following scientific databases: PubMed, Cochrane Library, and IEEE Xplore. The targeted search identified 1992 articles that were potentially eligible for inclusion, but, following title, abstract, and full-text review, only 6 articles were deemed to meet the inclusion criteria. Most studies performed adequately on measures of reporting, in and out of a laboratory environment, and found that sensor-derived data are successful in their respective objectives and goals. Nevertheless, we believe that additional studies utilizing standardized protocols should be conducted in the future to explore the impact and usefulness of wearable devices in gait-related characteristics such as fall prognosis and early diagnosis in people living with dementia.
Exploring the Contribution of Proximal Family Risk Factors on SLC6A4 DNA Methylation in Children with a History of Maltreatment: A Preliminary Study
Authors: Craig Francesco , Mascheroni Eleonora , Giorda Roberto , Felline Maria Grazia , Bacco Maria Grazia , Castagna Annalisa , Tenuta Flaviana , Villa Marco , Costabile Angela , Trabacca Antonio , Montirosso Rosario
Published: December 2021

The cumulative effects of proximal family risk factors have been associated with a high number of adverse outcomes in childhood maltreatment, and DNA methylation of the serotonin transporter gene (SLC6A4) has been associated with child maltreatment. However, the relationships between proximal family risk factors and SLC6A4 methylation remains unexplored. We examined the association among cumulative family risk factors, maltreatment experiences and DNA methylation in the SLC6A4 gene in a sample of 33 child victims of maltreatment. We computed a cumulative family risk (CFR) index that included proximal family risk factors, such as drug or alcohol abuse, psychopathology, parents’ experiences of maltreatment/abuse in childhood, criminal history, and domestic violence. The majority of children (90.9%) experienced more than one type of maltreatment. Hierarchical regression models suggested that the higher the CFR index score and the number of maltreatment experiences, and the older the children, the higher the SLC6A4 DNA methylation levels. Although preliminary, our findings suggest that, along with childhood maltreatment experiences per se, cumulative proximal family risk factors are seemingly critically associated with DNA methylation at the SLC6A4 gene.
Walking Engagement in Mexican Americans Who Participated in a Community-Wide Step Challenge in El Paso, TX
Authors: Saadiq Stefan , Valenzuela Roy , Wang Jing , Yin Zenong , Parra-Medina Deborah , Gay Jennifer , Salinas Jennifer
Published: December 2021

In the United States, the Latinx population has the highest prevalence of physical inactivity compared with other ethnicities. Research shows that work-based physical activity interventions have been widely implemented in the non-Latinx population and effectively increase physical activity in the non-Latinx population. In an effort to improve physical activity and reduce obesity among the Latinx population, we conducted 10,000 Steps for 100 Days, an employer-based walking challenge campaign, to increase walking engagement among Latinx employees located in El Paso, Texas. Participants reported their number of steps using a pedometer or smartphone. Step counts were collected at baseline, 2 weeks post challenge, and 6 months post challenge. Screenshots of the tracking device were uploaded to an online tracker. Regression analysis was conducted to identify covariates associated with baseline and 2-week and 6-month average daily steps. Generalized estimating equations (GEE) were performed to predict steps over time by demographic characteristics. Participation in the 10,000 Steps for 100 Days walking challenge was associated with a sustained increase in average daily steps. Participants with less than 7000 steps per day demonstrated the greatest increase in average daily steps (921 steps at 2 weeks; 1002.4 steps at 6 months). Demographic characteristics were not significant predictors of average steps, except that married participants had higher average steps. Participants with 10,000 or more daily steps had a 51% (p = 0.031) higher chance of having a professional occupation than a non-professional one compared to those with 7000 or fewer daily steps. We provided initial evidence that the walking challenge is an effective approach for improving physical activity in the Latinx population.
Role and Perspectives of Inflammation and C-Reactive Protein (CRP) in Psychosis: An Economic and Widespread Tool for Assessing the Disease
Authors: Ullah Irfan , Awan Hashir Ali , Aamir Alifiya , Diwan Mufaddal Najmuddin , de Filippis Renato , Awan Sana , Irfan Muhammad , Fornaro Michele , Ventriglio Antonio , Vellante Federica , Pettorruso Mauro , Martinotti Giovanni , Di Giannantonio Massimo , De Berardis Domenico
Published: December 2021

Schizophrenia is a major psychotic disorder affecting nearly 23.6 million people globally and greatly impacting the cognitive and social functioning of individuals. Multiple risk factors, including genetic, environmental, and epigenetic factors have been identified. However, the exact mechanism by which some factors aid in the development of schizophrenia is still uncertain. Acute and/or long-standing inflammation has been implicated as both a cause and effect of schizophrenia. Heightened immune responses have been documented in large cohorts of individuals with schizophrenia. While not completely known, multiple hypotheses, such as disruption of the blood–brain barrier, alterations in the kynurenine/tryptophan pathway, and increased microglial activation, have been presented to correlate inflammation with schizophrenic symptoms. Measurement of C-reactive protein (CRP) is a commonly performed and inexpensive test on patients’ serum to determine levels of systemic inflammation in the body. Multiple studies have reported an elevated CRP level in different stages of schizophrenia, indicating its potential to be used as a viable biomarker in the diagnosis and monitoring of schizophrenia along with assessing treatment response to conventional and non-conventional treatment regimens. This review aims to evaluate the role of inflammation, in general, and CRP, in particular, in the pathogenesis of schizophrenia and its potential significance in diagnostic, therapeutic, and preventative approaches towards schizophrenia and psychosis.
Selenium-Containing Exopolysaccharides Isolated from the Culture Medium of Lentinula edodes: Structure and Biological Activity
Authors: Górska-Jakubowska Sandra , Klimaszewska Marzenna , Podsadni Piotr , Kaleta Beata , Zagożdżon Radosław , Górska Sabina , Gamian Andrzej , Strączek Tomasz , Kapusta Czesław , Cieślak Marcin , Kaźmierczak-Barańska Julia , Nawrot Barbara , Turło Jadwiga
Published: December 2021

In continuation of our research on the influence of selenium incorporation on the biosynthesis, structure, and immunomodulatory and antioxidant activities of polysaccharides of fungal origin, we have isolated from a post-culture medium of Lentinula edodes a selenium (Se)-containing exopolysaccharide fraction composed mainly of a highly branched 1-6-α-mannoprotein of molecular weight 4.5 × 106 Da, with 15% protein component. The structure of this fraction resembled mannoproteins isolated from yeast and other mushroom cultures, but it was characterized by a significantly higher molecular weight. X-ray absorption fine structure spectral analysis in the near edge region (XANES) suggested that selenium in the Se-exopolysaccharide structure was present mainly at the IV oxidation state. The simulation analysis in the EXAFS region suggested the presence of two oxygen atoms in the region surrounding the selenium. On the grounds of our previous studies, we hypothesized that selenium-enriched exopolysaccharides would possess higher biological activity than the non-Se-enriched reference fraction. To perform structure–activity studies, we conducted the same tests of biological activity as for previously obtained mycelial Se-polyglucans. The Se-enriched exopolysaccharide fraction significantly enhanced cell viability when incubated with normal (human umbilical vein endothelial cells (HUVEC)) cells (but this effect was absent for malignant human cervical HeLa cells) and this fraction also protected the cells from oxidative stress conditions. The results of tests on the proliferation of human peripheral blood mononuclear cells suggested a selective immunosuppressive activity, like previously tested Se-polyglucans isolated from L. edodes mycelium. The Se-exopolysaccharide fraction, in concentrations of 10–100 µg/mL, inhibited human T lymphocyte proliferation induced by mitogens, without significant effects on B lymphocytes. As with previously obtained Se-polyglucans, in the currently tested Se-polymannans, the selenium content increased the biological activity. However, the activity of selenium exopolysaccharides in all tests was significantly lower than that of previously tested mycelial isolates, most likely due to a different mode of selenium binding and its higher degree of oxidation.
NCs-Delivered Pesticides: A Promising Candidate in Smart Agriculture
Authors: Hou Qiuli , Zhang Hanqiao , Bao Lixia , Song Zeyu , Liu Changpeng , Jiang Zhenqi , Zheng Yang
Published: December 2021

Pesticides have been used extensively in the field of plant protection to maximize crop yields. However, the long-term, unmanaged application of pesticides has posed severe challenges such as pesticide resistance, environmental contamination, risk in human health, soil degradation, and other important global issues. Recently, the combination of nanotechnology with plant protection strategies has offered new perspectives to mitigate these global issues, which has promoted a rapid development of NCs-based pesticides. Unlike certain conventional pesticides that have been applied inefficiently and lacked targeted control, pesticides delivered by nanocarriers (NCs) have optimized formulations, controlled release rate, and minimized or site-specific application. They are receiving increasing attention and are considered as an important part in sustainable and smart agriculture. This review discussed the limitation of traditional pesticides or conventional application mode, focused on the sustainable features of NCs-based pesticides such as improved formulation, enhanced stability under harsh condition, and controlled release/degradation. The perspectives of NCs-based pesticides and their risk assessment were also suggested in this view for a better use of NCs-based pesticides to facilitate sustainable, smart agriculture in the future.
Microglia-Derived Olfactomedin-like 3 Promotes Pro-Tumorigenic Microglial Function and Malignant Features of Glioma Cells
Authors: Toedebusch Ryan G. , Lucchesi Christopher A. , Debebe Eshetu T. , Wittenburg Luke A. , Chen Xinbin , Toedebusch Christine M.
Published: December 2021

Under the influence of transforming growth factor-beta (TGFβ), glioma-associated microglia produce molecules that promote glioma growth and invasion. Olfactomedin-like 3 (Olfml3), a novel, secreted glycoprotein, is known to promote several non-CNS cancers. While it is a direct TGFβ1 target gene in microglia, the role of microglia-derived OLFML3 in glioma progression is unknown. Here, we tested the hypotheses that microglial Olfml3 is integral to the pro-tumorigenic glioma-associated microglia phenotype and promotes glioma cell malignancy. Using an Olfml3 knockout microglial cell line (N9), we demonstrated that Olfml3 is a direct target gene of all TGFβ isoforms in murine microglia. Moreover, loss of Olfml3 attenuated TGFβ-induced restraint on microglial immune function and production of cytokines that are critical in promoting glioma cell malignancy. Importantly, microglia-derived OLFML3 directly contributes to glioma cell malignancy through increased migration and invasion. While exposure to conditioned medium (CM) from isogenic control microglia pre-treated with TGFβ increased mouse glioma cell (GL261) migration and invasion, this effect was abolished with exposure to CM from TGFβ-treated Olfml3-/- microglia. Taken together, our data suggest that Olfml3 may serve as a gatekeeper for TGFβ-induced microglial gene expression, thereby promoting the pro-tumorigenic microglia phenotype and glioma cell malignancy.
Mitochondrial Biogenesis in Neurons: How and Where
Authors: Cardanho-Ramos Carlos , Morais Vanessa Alexandra
Published: December 2021

Neurons rely mostly on mitochondria for the production of ATP and Ca2+ homeostasis. As sub-compartmentalized cells, they have different pools of mitochondria in each compartment that are maintained by a constant mitochondrial turnover. It is assumed that most mitochondria are generated in the cell body and then travel to the synapse to exert their functions. Once damaged, mitochondria have to travel back to the cell body for degradation. However, in long cells, like motor neurons, this constant travel back and forth is not an energetically favourable process, thus mitochondrial biogenesis must also occur at the periphery. Ca2+ and ATP levels are the main triggers for mitochondrial biogenesis in the cell body, in a mechanism dependent on the Peroxisome-proliferator-activated γ co-activator-1α-nuclear respiration factors 1 and 2-mitochondrial transcription factor A (PGC-1α-NRF-1/2-TFAM) pathway. However, even though of extreme importance, very little is known about the mechanisms promoting mitochondrial biogenesis away from the cell body. In this review, we bring forward the evoked mechanisms that are at play for mitochondrial biogenesis in the cell body and periphery. Moreover, we postulate that mitochondrial biogenesis may vary locally within the same neuron, and we build upon the hypotheses that, in the periphery, local protein synthesis is responsible for giving all the machinery required for mitochondria to replicate themselves.
Molecular Bases of Human Malformation Syndromes Involving the SHH Pathway: GLIA/R Balance and Cardinal Phenotypes
Authors: Niida Yo , Togi Sumihito , Ura Hiroki
Published: December 2021

Human hereditary malformation syndromes are caused by mutations in the genes of the signal transduction molecules involved in fetal development. Among them, the Sonic hedgehog (SHH) signaling pathway is the most important, and many syndromes result from its disruption. In this review, we summarize the molecular mechanisms and role in embryonic morphogenesis of the SHH pathway, then classify the phenotype of each malformation syndrome associated with mutations of major molecules in the pathway. The output of the SHH pathway is shown as GLI activity, which is generated by SHH in a concentration-dependent manner, i.e., the sum of activating form of GLI (GLIA) and repressive form of GLI (GLIR). Which gene is mutated and whether the mutation is loss-of-function or gain-of-function determine in which concentration range of SHH the imbalance occurs. In human malformation syndromes, too much or too little GLI activity produces symmetric phenotypes affecting brain size, craniofacial (midface) dysmorphism, and orientation of polydactyly with respect to the axis of the limb. The symptoms of each syndrome can be explained by the GLIA/R balance model.
Natural Dibenzo-α-Pyrones: Friends or Foes?
Authors: Aichinger Georg
Published: December 2021

Natural dibenzo-α-pyrones (DAPs) can be viewed from two opposite angles. From one angle, the gastrointestinal metabolites urolithins are regarded as beneficial, while from the other, the emerging mycotoxin alternariol and related fungal metabolites are evaluated critically with regards to potential hazardous effects. Thus, the important question is: can the structural characteristics of DAP subgroups be held responsible for distinct bioactivity patterns? If not, certain toxicological and/or pharmacological aspects of natural DAPs might yet await elucidation. Thus, this review focuses on comparing published data on the two groups of natural DAPs regarding both adverse and beneficial effects on human health. Literature on genotoxic, estrogenic, endocrine-disruptive effects, as well as on the induction of the cellular anti-oxidative defense system, anti-inflammatory properties, the inhibition of kinases, the activation of mitophagy and the induction of autophagy, is gathered and critically reviewed. Indeed, comparing published data suggests similar bioactivity profiles of alternariol and urolithin A. Thus, the current stratification into hazardous Alternaria toxins and healthy urolithins seems debatable. An extrapolation of bioactivities to the other DAP sub-class could serve as a promising base for further research. Conclusively, urolithins should be further evaluated toward high-dose toxicity, while alternariol derivatives could be promising chemicals for the development of therapeutics.
Sustainable Stabilizer-Free Nanoparticle Formulations of Valsartan Using Eudragit® RLPO
Authors: Hajba-Horváth Eszter , Fodor-Kardos Andrea , Shah Nishant , Wacker Matthias G. , Feczkó Tivadar
Published: December 2021

The bioavailability of the antihypertensive drug valsartan can be enhanced by various microencapsulation methods. In the present investigation, valsartan-loaded polymeric nanoparticles were manufactured from Eudragit® RLPO using an emulsion–solvent evaporation method. Polyvinyl alcohol (PVA) was found to be a suitable stabilizer for the nanoparticles, resulting in a monodisperse colloid system ranging in size between 148 nm and 162 nm. Additionally, a high encapsulation efficiency (96.4%) was observed. However, due to the quaternary ammonium groups of Eudragit® RLPO, the stabilization of the dispersion could be achieved in the absence of PVA as well. The nanoparticles were reduced in size (by 22%) and exhibited similar encapsulation efficiencies (96.4%). This more cost-effective and sustainable production method reduces the use of excipients and their expected emission into the environment. The drug release from valsartan-loaded nanoparticles was evaluated in a two-stage biorelevant dissolution set-up, leading to the rapid dissolution of valsartan in a simulated intestinal medium. In silico simulations using a model validated previously indicate a potential dose reduction of 60–70% compared to existing drug products. This further reduces the expected emission of the ecotoxic compound into the environment.
Genomic Variants and Multilevel Regulation of ABCA1, ABCG1, and SCARB1 Expression in Atherogenesis
Authors: Rozhkova Alexandra V. , Dmitrieva Veronika G. , Nosova Elena V. , Dergunov Alexander D. , Limborska Svetlana A. , Dergunova Liudmila V.
Published: December 2021

Atheroprotective properties of human plasma high-density lipoproteins (HDLs) are determined by their involvement in reverse cholesterol transport (RCT) from the macrophage to the liver. ABCA1, ABCG1, and SR-BI cholesterol transporters are involved in cholesterol efflux from macrophages to lipid-free ApoA-I and HDL as a first RCT step. Molecular determinants of RCT efficiency that may possess diagnostic and therapeutic meaning remain largely unknown. This review summarizes the progress in studying the genomic variants of ABCA1, ABCG1, and SCARB1, and the regulation of their function at transcriptional and post-transcriptional levels in atherosclerosis. Defects in the structure and function of ABCA1, ABCG1, and SR-BI are caused by changes in the gene sequence, such as single nucleotide polymorphism or various mutations. In the transcription initiation of transporter genes, in addition to transcription factors, long noncoding RNA (lncRNA), transcription activators, and repressors are also involved. Furthermore, transcription is substantially influenced by the methylation of gene promoter regions. Post-transcriptional regulation involves microRNAs and lncRNAs, including circular RNAs. The potential biomarkers and targets for atheroprotection, based on molecular mechanisms of expression regulation for three transporter genes, are also discussed in this review.
Diagnostic Yield of Transbronchial Lung Cryobiopsy Compared to Transbronchial Forceps Biopsy in Patients with Sarcoidosis in a Prospective, Randomized, Multicentre Cross-Over Trial
Authors: Häntschel Maik , Eberhardt Ralf , Petermann Christoph , Gesierich Wolfgang , Darwiche Kaid , Hagmeyer Lars , Colby Thomas V. , Fend Falko , Theegarten Dirk , Wintzer Hanns-Olof , Kreuter Michael , Spengler Werner , Behrens-Zemek Annika Felicitas , Lewis Richard A. , Evrard Henry C. , Ehab Ahmed , Böckeler Michael , Hetzel Jürgen
Published: December 2021

Background: Transbronchial lung forceps biopsy (TBLF) is of limited value for the diagnosis of interstitial lung disease (ILD). However, in cases with predominantly peribronchial pathology, such as sarcoidosis, TBLF is considered to be diagnostic in most cases. The present study examines whether transbronchial lung cryobiopsy (TBLC) is superior to TBLF in terms of diagnostic yield in cases of sarcoidosis. Methods: In this post hoc analysis of a prospective, randomized, controlled, multicentre study, 359 patients with ILD requiring diagnostic bronchoscopic tissue sampling were included. TBLF and TBLC were both used for each patient in a randomized order. Histological assessment was undertaken on each biopsy and determined whether sarcoid was a consideration. Results: A histological diagnosis of sarcoidosis was established in 17 of 272 cases for which histopathology was available. In 6 out of 17 patients, compatible findings were seen with both TBLC and TBLF. In 10 patients, where the diagnosis of sarcoidosis was confirmed by TBLC, TBLF did not provide a diagnosis. In one patient, TBLF but not TBLC confirmed the diagnosis of sarcoidosis. Conclusions: In this post hoc analysis, the histological diagnosis of sarcoidosis was made significantly more often by TBLC than by TBLF. As in other idiopathic interstitial pneumonias (IIPs), the use of TBLC should be considered when sarcoidosis is suspected.
Emergence of Solitons from Irregular Waves in Deep Water
Authors: Xia Weida , Ma Yuxiang , Dong Guohai , Zhang Jie , Ma Xiaozhou
Published: December 2021

Numerical simulations were performed to study the long-distance evolution of irregular waves in deep water. It was observed that some solitons, which are the theoretical solutions of the nonlinear Schrödinger equation, emerged spontaneously as irregular wave trains propagated in deep water. The solitons propagated approximately at a speed of the linear group velocity. All the solitons had a relatively large amplitude and one detected soliton’s height was two times larger than the significant wave height of the wave train, therefore satisfying the rogue wave definition. The numerical results showed that solitons can persist for a long distance, reaching about 65 times the peak wavelength. By analyzing the spatial variations of these solitons in both time and spectral domains, it is found that the third-and higher-order resonant interactions and dispersion effects played significant roles in the formation of solitons.
Prognostic Value of C-Reactive Protein to Lymphocyte Ratio (CLR) in Emergency Department Patients with SARS-CoV-2 Infection
Authors: Tonduangu Ndenga , Le Borgne Pierrick , Lefebvre François , Alame Karine , Bérard Lise , Gottwalles Yannick , Cipolat Lauriane , Gennai Stéphane , Bilbault Pascal , Lavoignet Charles-Eric , Abensur Vuillaume Laure ,   on behalf of CREMS Network (Clinical Research in Emergency Medicine and Sepsis) (CLR)
Published: December 2021

(1) Introduction: According to recent studies, the ratio of C-reactive-protein to lymphocyte is more sensitive and specific than other biomarkers associated to systemic inflammatory processes. This study aimed to determine the prognostic value of CLR on COVID-19 severity and mortality at emergency department (ED) admission. (2) Methods: Between 1 March and 30 April 2020, we carried out a multicenter and retrospective study in six major hospitals of northeast France. The cohort was composed of patients hospitalized for a confirmed diagnosis of moderate to severe COVID-19. (3) Results: A total of 1,035 patients were included in this study. Factors associated with infection severity were the CLR (OR: 1.001, CI 95%: (1.000–1.002), p = 0.012), and the lymphocyte level (OR: 1.951, CI 95%: (1.024–3.717), p = 0.042). In multivariate analysis, the only biochemical factor significantly associated with mortality was lymphocyte rate (OR: 2.308, CI 95%: (1.286–4.141), p = 0.005). The best threshold of CLR to predict the severity of infection was 78.3 (sensitivity 79%; specificity 47%), and to predict mortality, was 159.5 (sensitivity 48%; specificity 70%). (4) Conclusion: The CLR at admission to the ED could be a helpful prognostic biomarker in the early screening and prediction of the severity and mortality associated with SARS-CoV-2 infection.
Psychosis in Women: Time for Personalized Treatment
Authors: Mazza Marianna , Caroppo Emanuele , De Berardis Domenico , Marano Giuseppe , Avallone Carla , Kotzalidis Georgios D. , Janiri Delfina , Moccia Lorenzo , Simonetti Alessio , Conte Eliana , Martinotti Giovanni , Janiri Luigi , Sani Gabriele
Published: December 2021

Early detection and prompt treatment of psychosis is of the utmost importance. The great variability in clinical onset, illness course, and response to pharmacological and psychosocial treatment is in great part gender-related. Our aim has been to review narratively the literature focusing on gender related differences in the psychoses, i.e., schizophrenia spectrum disorders. We searched the PubMed/Medline, Scopus, Embase, and ScienceDirect databases on 31 July 2021, focusing on recent research regarding sex differences in early psychosis. Although women, compared to men, tend to have better overall functioning at psychotic symptom onset, they often present with more mood symptoms, may undergo misdiagnosis and delay in treatment and are at a higher risk for antipsychotic drug-induced metabolic and endocrine-induced side effects. Furthermore, women with schizophrenia spectrum disorders have more than double the odds of having physical comorbidities than men. Tailored treatment plans delivered by healthcare services should consider gender differences in patients with a diagnosis of psychosis, with a particular attention to early phases of disease in the context of the staging model of psychosis onset.
COVID-19 Vaccine Does Not Increase the Risk of Disease Flare-Ups among Patients with Autoimmune and Immune-Mediated Diseases
Authors: Pinte Larisa , Negoi Florentina , Ionescu Georgeta Daniela , Caraiola Simona , Balaban Daniel Vasile , Badea Camelia , Mazilu Diana , Dumitrescu Bianca , Mateescu Bogdan , Ionescu Ruxandra , Parvu Magda Ileana , Baicus Cristian
Published: December 2021

Background: Reports describing post-vaccine autoimmune phenomena, in previously healthy individuals, increased the concerns regarding the risk of disease flare-ups in patients with immune diseases. We aimed to assess the potential risk of disease flare-up, after receiving the COVID-19 (Coronavirus disease 2019) vaccine, during a follow-up period of 6 months. Methods: We performed a prospective cohort study, enrolling the patients with autoimmune- and immune-mediated diseases who voluntarily completed our questionnaire, both online and during hospital evaluations. Based on their decision to receive the vaccine, the patients were divided into two groups (vaccinated and non-vaccinated). Participants who chose not to receive the vaccine served as a control group in terms of flare-ups. Results: A total of 623 patients, 416 vaccinated and 207 non-vaccinated, were included in the study during hospital evaluations (222/623) and after online (401/623) enrolment. There was no difference concerning the risk of flare-up between vaccinated and non-vaccinated patients (1.16, versus 1.72 flare-ups/100 patients-months, p = 0.245). The flare-ups were associated with having more than one immune disease, and with a previous flare-up during the past year. Conclusions: We did not find an increased risk of flare-up following COVID-19 vaccination in patients with autoimmune-/immune-mediated diseases, after a median follow-up of 5.9 months. According to our results, there should not be an obvious reason for vaccine hesitancy among this category of patients.
Relative Risk Prediction of Norovirus Incidence under Climate Change in Korea
Authors: Kim Tae-Kyoung , Paek Jayeong , Kim Hwang-Yong , Choi Ilsu
Published: December 2021

As incidences of food poisoning, especially norovirus-induced diarrhea, are associated with climate change, there is a need for an approach that can be used to predict the risks of such illnesses with high accuracy. In this paper, we predict the winter norovirus incidence rate in Korea compared to that of other diarrhea-causing viruses using a model based on B-spline added to logistic regression to estimate the long-term pattern of illness. We also develop a risk index based on the estimated probability of occurrence. Our probabilistic analysis shows that the risk of norovirus-related food poisoning in winter will remain stable or increase in Korea based on various Representative Concentration Pathway (RCP) scenarios. Our approach can be used to obtain an overview of the changes occurring in regional and seasonal norovirus patterns that can help assist in making appropriate policy decisions.
Facile and Controllable Preparation of Poly(St-co-MMA)/FA Microspheres Used as Ultra-Lightweight Proppants
Authors: Chen Tao , Sang Yanan , Zhou Yuxin , Ji Liudi , Han Xiaobing , Hu Peng , Miao Pengpai , Gao Jie , Zhao Yuan
Published: December 2021

Hydraulic fracturing is an important technology for the exploitation of unconventional oil or gas reservoirs. In order to increase the production of oil or gas, ultra-lightweight proppants with a high compressive strength are highly desirable in hydraulic fracture systems. In this work, a new type of ultra-lightweight proppant, poly(styrene-co-methyl methacrylate)/fly ash (poly(St-co-MMA)/FA) composites with a high compressive strength were prepared via in situ suspension polymerization. The Fourier transform infrared (IR) and X-ray powder diffraction (XRD) analyses confirmed that the poly(St-co-MMA)/FA composites were successfully prepared. The morphology analysis indicated that the composite microspheres show good sphericity, and FA powder was evenly dispersed in the matrix. The apparent density of the microspheres was between 1 and 1.3 g/cm3, which is suitable for hydraulic fracturing. Furthermore, the compressive strength and thermostability were dramatically improved with the incorporation of FA, which could withstand high pressures and temperatures underground. The obtained poly(St-co-MMA)/FA composite microspheres are promising for application as an ultra-lightweight (ULW) proppant in oil or gas exploitation, which provides a new approach for the design of high performance proppants.