bluuebunny/crossref_metadata_2025 huggingface dataset:
Mississippi Farmers’ Interest in and Experience with Farm to School
Authors: Thomson Jessica L. , Walls Tameka I. , Landry Alicia S.
Published: July 2022

The study’s purpose was to collect demographic and farm characteristics from Mississippi small farmers and to determine their abilities, experiences, and desires to engage in Farm to School (F2S) activities. The online survey was created using items taken from existing F2S surveys. Invitations to participate were sent via email to farmers beginning in October 2021 and ending in January 2022. Descriptive statistics were used to summarize the data. Of the 258 individuals with valid email addresses, 43 (17%) completed the online survey, and 38 fit the definition of small farm (<USD 250,000 in gross cash farm income). Mean farm acreage was 68 (range 1–480 acres). Twenty-six (70%) farms did not have any certifications. Common selling practices included farm stands/stores (n = 18; 49%) and farmers markets (n = 16; 43%). Only 4 farmers (11%) sold to schools with half indicating the experience was difficult. Common challenges included no relationship with school staff (n = 14; 44%) and guarantying quantity/date (n = 11; 34%). Twenty-six (68%) farmers expressed an interest in at least one F2S activity. To facilitate mutually beneficial relationships between small farmers and school food service staff, work is needed to connect the two groups and guide farmers in navigating school procurement rules and regulations.
Predictors of Land-Based Activity Participation in a National Representative Sample of Indigenous Individuals Living Off-Reserve
Authors: Toombs Elaine , Lund Jessie , Mushquash Aislin R. , Mushquash Christopher J.
Published: July 2022

This study examined data from the 2017 Aboriginal Peoples Survey to consider predictors of land-based activity engagement. We hypothesized that higher self-reported mental and physical health scores, an increased sense of cultural belonging, living in a rural community, and no prior individual or family history of residential school attendance would predict a higher frequency of land-based activity engagement among First Nations individuals living off-reserve. Results from linear regression analyses suggested that an increased sense of cultural belonging, being male, and living in a rural community with a population of less than 1000 people were significant predictors of the frequency of land-based activity engagement. With these preliminary findings, further research can explore how physical and mental health outcomes influence the frequency of land-based activity engagement, in addition to how community-specific indicators may promote higher frequency of these activities, particularly among First Nations individuals living off-reserve.
Distance Learning Support Measures for Teachers in Poland during the COVID-19 Pandemic
Authors: Cicha Karina , Rutecka Paulina , Rizun Mariia , Strzelecki Artur
Published: July 2022

The COVID-19 pandemic made higher education institutions switch to distance learning in a very short period of time. The situation was challenging not only for universities themselves but also for the students and teachers. Some universities did not have the means, in terms of infrastructure, for a smooth transition to distance learning. Some teachers were not prepared for the extensive usage of ICT in their work. The pandemic developed dynamically, and it made it extremely difficult for both governments and universities to plan and implement firm solutions on how to conduct the teaching process. The presented paper focuses on the situation of Polish higher education institutions between March 2020 and March 2022. It reviews legal acts and ordinances introduced in the stated period, which focused on the sustainability of the teaching process, countermeasures for the spread of COVID-19 and the implementation of distance learning. The case of the University of Economics in Katowice, Poland, is used to show the correlation between governmental legal acts and those introduced by the university as part of the COVID -19 spread prevention and teaching process support.
Predicting Return to Work Following Myocardial Infarction: A Prospective Longitudinal Cohort Study
Authors: Sun Weizhe , Gholizadeh Leila , Perry Lin , Kang Kyoungrim
Published: July 2022

This study aimed to determine the proportion of patients who returned to work within three months post-myocardial infarction and the factors that predicted return to work. A total of 136 participants with myocardial infarction completed the study questionnaires at baseline and three months post-discharge between August 2015 and February 2016. At the three-month follow-up, 87.5% (n = 49) of the participants who were working pre-infarction had resumed work. Age, gender, education, smoking, readmission after discharge, number of comorbidities, diabetes, social support, anxiety, and depression were significantly associated with returning to work at three months post-discharge. Age, gender, smoking, anxiety, and depression significantly predicted those patients with myocardial infarction that returned to work, using binary logistic regression. The majority of patients in work who experience myocardial infarction have the capacity to achieve a work resumption by three months post-discharge. Interventions that facilitate returning to work should focus on modifiable risk factors, such as improving these patients’ mental health, comorbid conditions, risk of readmission, smoking, and social support. Healthcare providers should work in partnership with patients’ family members, friends, and employers in developing and implementing interventions to address these modifiable factors to facilitate patients’ return to work.
Achieving Environmental Sustainability in Africa: The Role of Renewable Energy Consumption, Natural Resources, and Government Effectiveness—Evidence from Symmetric and Asymmetric ARDL Models
Authors: Yang Li , Bashiru Danwana Sumaiya , Issahaku Fadilul-lah Yassaanah
Published: July 2022

This study investigates the symmetric and asymmetric linkages within environmental sustainability proxied by ecological footprint (EFP), natural resources (NRR), renewable energy consumption (REC), urbanization (URB), human capital (HC), and government effectiveness (GE) in 27 African countries divided into two subgroups (ecological deficit countries and ecological reserve countries) over the period 1990 to 2018. The study employs the auto-regressive distributed lag (ARDL) model to investigate the symmetric (linear) effect and the nonlinear auto-regressive distributed lag (NARDL) model to study the asymmetric (nonlinear) effects of the variables on EFP. Results of ARDL show that a 1% increase in REC is projected to reduce ecological footprint by 0.17 and 0.2% in ecological deficit and ecological reserve countries. A 1% increase in NRR is estimated to increase ecological footprint by 0.02% in ecological deficit countries but has no impact on the environment in countries with ecological reserves. Similarly, a 1% rise in GE is estimated to increase EFP by 0.04% in Africa but has no impact on the environment in ecological deficit countries. NARDL estimations decomposed REC into positive (negative) shocks, which show that a 1% increase (decrease) in REC is projected to decrease EFP by 0.16% (0.13%) in countries with ecological reserves. Similarly, a positive (negative) shock in NRR is expected to decrease EFP in ecological reserve countries and increase EFP in ecological deficit countries. Results of the Wald tests prove the existence of long-run asymmetry among the variables. The findings indicate that renewable energy consumption enhances environmental quality, while economic growth and natural resource rents reduce environmental quality in Africa over the sampled period.
Evaluating the Public Climate School—A School-Based Programme to Promote Climate Awareness and Action in Students: Protocol of a Cluster-Controlled Pilot Study
Authors: Eichinger Michael , Bechtoldt Myriam , Bui Inga Thao My , Grund Julius , Keller Jan , Lau Ashley G. , Liu Shuyan , Neuber Michael , Peter Felix , Pohle Carina , Reese Gerhard , Schäfer Fabian , Heinzel Stephan
Published: July 2022

Introduction: School-based programmes may promote knowledge and skills required to address climate change and better health and well-being in adolescents, yet evidence of their effectiveness is limited. In preparation for evaluating the Public Climate School, a school-based intervention to promote climate awareness and action in adolescents, we conduct a pilot study intended to assess procedures for participant recruitment, retention, and data collection, data quality issues and to provide preliminary parameter estimates to guide sample size calculations. Methods and analysis: This unblinded, cluster-controlled pilot study targets students in twelve classes from grades seven to thirteen in German public schools. Seven and five classes were allocated to the intervention and waitlist control arms, respectively. The intervention consisted of (1) live lessons on YouTube, (2) climate-related challenges of the day, (3) workshops and (4) peer exchange sessions. Waitlist control classes participated three weeks later. Measures included the proportion of students completing baseline and follow-up surveys, a comparison of baseline characteristics between students in the retained subsample and those lost to follow-up, proportions of students completing online and paper–pencil-based surveys and problems during data collection based on information reported by teachers. Data quality was assessed as proportions of missing data, associations between missingness and sociodemographic measures using logistic regression models and basic psychometric properties of scales including ceiling effects and internal consistency. Intentions to reduce one’s ecological footprint, the primary outcome, and all secondary outcomes for effect estimation were assessed one week pre- and post-intervention from November to December 2021 using items adapted from internationally used instruments and will be investigated using generalised linear mixed models and intention-to-treat analyses. Conclusions: The pilot study will lay the methodological groundwork for a large-scale cluster-randomised effectiveness and process evaluation of the Public Climate School. If proven effective and rolled out more broadly, the Public Climate School has the potential to contribute meaningfully to national climate mitigation and adaptation efforts by reaching a substantial share of adolescents in public schools, including those traditionally less involved in climate action.
Association of Serum Levels of Plasticizers Compounds, Phthalates and Bisphenols, in Patients and Survivors of Breast Cancer: A Real Connection?
Authors: Segovia-Mendoza Mariana , Palacios-Arreola Margarita Isabel , Monroy-Escamilla Luz María , Soto-Piña Alexandra Estela , Nava-Castro Karen Elizabeth , Becerril-Alarcón Yizel , Camacho-Beiza Roberto , Aguirre-Quezada David Eduardo , Cardoso-Peña Elías , Amador-Muñoz Omar , Garduño-García José de Jesús , Morales-Montor Jorge
Published: July 2022

Phthalates and bisphenols are ubiquitous environmental pollutants with the ability to perturb different systems. Specifically, they can alter the endocrine system, and this is why they are also known as endocrine-disrupting compounds (EDCs). Interestingly, they are related to the development and progression of breast cancer (BC), but the threshold concentrations at which they trigger that are not well established. Objectives: The aim of this study was to compare the concentration measures of parent EDCs in three groups of women (without BC, with BC, and BC survivors) from two urban populations in Mexico, to establish a possible association between EDCs and this disease. We consider the measure of the parent compounds would reflect the individual’s exposure. Methods: The levels of di-ethyl-hexyl-phthalate (DEHP), butyl-benzyl-phthalate (BBP), di-n-butyl phthalate (DBP) and di-ethyl-phthalate (DEP), bisphenol A (BPA) and bisphenol S (BPS) were determined by gas chromatograph-mass spectrometry in 102 subjects, including 37 women without any pathological disease, 46 patients with BC and 19 women survivals of BC of Mexico and Toluca City. Results: All phthalates were detected in 100% of women, two of them were significantly higher in patients with different BC subtypes in Mexico City. Differential increases were observed mainly in the serum concentration of phthalates in women with BC compared to women without disease between Mexico and Toluca City. In addition, when performing an analysis of the concentrations of phthalates by molecular type of BC, DEP and BBP were found mainly in aggressive and poorly differentiated types of BC. It should be noted that female BC survivors treated with anti-hormonal therapy showed lower levels of BBP than patients with BC. BPA and BPS were found in most samples from Mexico City. However, BPS was undetectable in women from Toluca City. Discussion: The results of our study support the hypothesis of a positive association between exposure to phthalates and BC incidence.
From Research into Practice: Converting Epidemiological Data into Relevant Information for Planning of Regional Health Services for Refugees in Germany
Authors: Hintermeier Maren , Gold Andreas W. , Erdmann Stella , Perplies Clara , Bozorgmehr Kayvan , Biddle Louise
Published: July 2022

Health data of refugees and asylum seekers (ASR) is not routinely collected in Germany. Based on health data of ASR collected in 2018 in regional accommodation centres, we developed a dashboard to estimate regional burden of disease in Baden-Wuerttemberg, Germany. We aimed to find out how scientific data can support actors involved in healthcare planning for ASR in Germany and, within this scope, to explore how healthcare planning is conducted in this context. We conducted 12 qualitative semi-structured interviews including a usability test for a health data dashboard with regional decision-makers. Results showed that healthcare planning processes for ASR in Germany involve a complex set of actors in both long- and short-term decision-making. Data gained from representative surveys can support long-term decision-making and thus support the resilience of the health system, but it must balance the need for simple data presentation with transparent communication of potentially complex methods.
Research on Schistosomiasis in the Era of the COVID-19 Pandemic: A Bibliometric Analysis
Authors: Sánchez-Marqués Raquel , Mas-Coma Santiago , Salas-Coronas Joaquín , Boissier Jerôme , Bargues María Dolores
Published: July 2022

The objectives of this work are to check whether the COVID-19 pandemic affected the research on schistosomiasis, to provide an insight into the most productive countries and journals and the most cited publications, and to analyse any association between the total publications of countries and a set of socio-economic and demographic factors. Based on PRISMA methodology, we used the Scopus database to search for articles published between 1 January 2020 and 26 March 2022. VOSviewer was used to generate the co-authorship and the co-occurrence networks, and Spearman’s rank correlation was applied to study associations. A total of 1988 articles were included in the study. Although we found that the year-wise distribution of publications suggests no impact on schistosomiasis research, many resources have been devoted to research on COVID-19, and the Global Schistosomiasis Alliance revealed the main activities for eradication of schistosomiasis had been affected. The most productive country was the United States of America. The articles were mainly published in PLoS Neglected Tropical Diseases. The most prolific funding institution was the National Natural Science Foundation of China. The total publications per country were significantly correlated with population, GERD, and researchers per million inhabitants, but not with GDP per capita and MPM.
Detection of COVID-19 Patients Using Machine Learning Techniques: A Nationwide Chilean Study
Authors: Ormeño Pablo , Márquez Gastón , Guerrero-Nancuante Camilo , Taramasco Carla
Published: July 2022

Epivigila is a Chilean integrated epidemiological surveillance system with more than 17,000,000 Chilean patient records, making it an essential and unique source of information for the quantitative and qualitative analysis of the COVID-19 pandemic in Chile. Nevertheless, given the extensive volume of data controlled by Epivigila, it is difficult for health professionals to classify vast volumes of data to determine which symptoms and comorbidities are related to infected patients. This paper aims to compare machine learning techniques (such as support-vector machine, decision tree and random forest techniques) to determine whether a patient has COVID-19 or not based on the symptoms and comorbidities reported by Epivigila. From the group of patients with COVID-19, we selected a sample of 10% confirmed patients to execute and evaluate the techniques. We used precision, recall, accuracy, F1-score, and AUC to compare the techniques. The results suggest that the support-vector machine performs better than decision tree and random forest regarding the recall, accuracy, F1-score, and AUC. Machine learning techniques help process and classify large volumes of data more efficiently and effectively, speeding up healthcare decision making.
How to Increase Job Satisfaction and Performance? Start with Thriving: The Serial Mediation Effect of Psychological Capital and Burnout
Authors: Okros Norberth , Vîrgă Delia
Published: July 2022

Based on the Job Demands-Resources and Broaden and Build theories, this study examines the role of thriving at work and psychological capital on burnout and, ultimately, job satisfaction and performance one year later. We used structural equation modeling to test the model on a sample of 317 Romanian correctional officers in a two-wave study at T1 and one year later (T2). The results indicate that thriving at work at Time 1 is positively linked to psychological capital at Time 1, and negatively related to burnout at Time 2. Meanwhile, burnout at Time 2 is negatively related to job satisfaction and performance at Time 2. The mediating chain effect of psychological capital at Time 1 and burnout at Time 2 is significant. Thriving at work and psychological capital are essential factors contributing to a decrease in subsequent burnout and increased job satisfaction and performance. In a thriving environment, correctional officers are more resilient, confident, optimistic, and hopeful at work, generating lower burnout over time and increasing job satisfaction and performance. Supervisors need to be encouraged to create a thriving work environment to increase psychological capital, reduce burnout, and improve correctional officers’ satisfaction and performance.
Does Older Age Modify Associations between Endocrine Disrupting Chemicals and Fecundability?
Authors: Pollack Anna Z. , Krall Jenna R. , Swan Shanna H. , Louis Germaine M. Buck
Published: July 2022

Urinary concentrations of several endocrine disrupting chemicals, including phthalate metabolites, bisphenol A (BPA), and benzophenone (BP)-type ultraviolet (UV) filters, have been associated with a longer time-to-pregnancy (TTP). Potential modification of these associations by couple’s age has not been studied. TTP was defined as the number of prospectively observed menstrual cycles a couple attempted pregnancy until the occurrence of a human chorionic gonadotropic-detected pregnancy. Urinary concentrations of two BP-type UV filters and three phthalate metabolites were measured at baseline. Fecundability odds ratios (FORs) and 95% confidence intervals (CIs) were estimated for each chemical adjusting for age, body mass index, serum cotinine, creatinine, and accounting for right censoring and left truncation. Models evaluated effect modification between EDC concentrations and TTP by partner’s age, dichotomized at 35 years. Separate models were run for male and female partners. No significant effect modification was observed for any EDC for either partner, but data were suggestive of a longer TTP among females aged ≥35 years, particularly for BP-2 (FOR = 0.61, 95% CI 0.36, 1.05) and 4-hydroxybenzophenone (FOR = 0.71, 95% CI: 0.46, 1.09) reflecting 39% and 29% reductions in fecundability, respectively. We saw no evidence of effect modification by couples’ age on associations between TTP and urinary phthalate or BPA metabolite concentrations. Across the EDCs we examined, we found little evidence that age modifies TTP-exposure associations.
Prevalence of Congenital Anomaly and Its Relationship with Maternal Education and Age According to Local Development in the Extreme South of Brazil
Authors: Anele Carolina Ribeiro , Goldani Marcelo Zubaran , Schüler-Faccini Lavínia , da Silva Clécio Homrich
Published: July 2022

Congenital anomalies (CA) contribute to disabilities and health conditions throughout life. Furthermore, they can cause emotional distress to the mothers and children, who may also experience limitations in individual and social development. This study investigated the prevalence of CA and the relationship with maternal education and age according to local development in the extreme south of Brazil. This is a retrospective observational study with birth data from the Live Birth Information System from 2000 to 2017. The association between age and maternal education with the presence of CA was verified using multiple Poisson regression for robust variances in models adjusted for those variables with a preliminary significant association. A total of 5131 (1.5%) had some CA identified at birth between 2000 and 2017. Only advanced age (≥36 years) was associated with CA regardless of macro-region development (p ≤ 0.001). The highest risk was observed in regions with medium development (RR = 1.60; 95% CI 1.30–1.97). Maternal education (<8 years of study) was associated with CA only in mothers from macro-regions with very high development (RR = 1.27; 95% CI 1.03–1.54). These analyses confirmed that women of advanced age are at greater risk of having children with a CA regardless of maternal education and local development, but social characteristics can also have an influence, as regions with higher development had lower prevalence of CA.
Cannabis Use and Parenting Practices among Young People: The Impact of Parenting Styles, Parental Cannabis-Specific Rules, and Parental Cannabis Use
Authors: Kokotovič Karmen Osterc , Pšunder Mateja , Kirbiš Andrej
Published: July 2022

Cannabis is the most commonly used illicit drug. Its use typically starts in adolescence, and parents play a key role in young people’s cannabis use. Our study aimed to examine and compare the effects of parenting styles, parental cannabis-specific rules, and parental cannabis use on young people’s cannabis use. The research sample consisted of 839 students from various secondary education programs in Slovenia, aged 14 to 21. Associations between the young people’s lifetime cannabis use and their experience of parenting practices were assessed using logistic regression, with demographic, socioeconomic, educational, health, and risk behaviors controlled in a multivariate model. Maternal authoritative parenting (in comparison with permissive parenting), strict maternal, cannabis-specific rules, and parental cannabis non-use statistically significantly reduced the likelihood of young people’s cannabis use. Its strongest predictor was parental cannabis use, followed by the mother’s specific cannabis-use rules and maternal parenting style. The findings of our study can contribute to the development of public health policies to more effectively prevent cannabis use among adolescents and emerging adults, including by designing prevention programs aimed at strengthening parents’ general and cannabis-specific practices and competences.
Mapping Urban Forms Worldwide: An Analysis of 8910 Street Networks and 25 Indicators
Authors: Zhou Qi , Bao Junya , Liu Helin
Published: July 2022

Understanding urban form is beneficial for planners and designers to improve the built environment. The street network, as an essential element of urban form, has received much attention from existing studies. Recently, an open dataset containing 8910 global urban street networks and 25 different form indicators has been produced, but the urban forms of cities across the globe have rarely been recognized based on analyzing such a large dataset, which was the main purpose of our study. We employed correlation analysis, principal component analysis and hierarchical clustering methods for analyzing this dataset. We also compared the spatial pattern of clustering results with those using terrain and land-cover data. Results show that: (1) Most of these indicators are highly correlated with at least another indicator, and six principal components (i.e., size, terrain-variation, regularity, long-street, circuity and altitude) were found. (2) Seven clusters (i.e., regular, long-street, large size, irregular, varied-terrain, high-circuity and high-altitude) of cities were identified; cities of the same cluster can be spatially aggregated and also distributed across different regions. (3) Most of these clusters can be interpreted using terrain and land-cover data, which indicates that the urban forms of most cities across the globe are related to geographical factors. The clustering results may be used not only to compare street networks and their urban forms at a global scale but also to understand the formation and development of an urban street network.
Analysis of the Hypoxic Response in a Mouse Cortical Collecting Duct-Derived Cell Line Suggests That Esrra Is Partially Involved in Hif1α-Mediated Hypoxia-Inducible Gene Expression in mCCDcl1 Cells
Authors: Keppner Anna , Maric Darko , Orlando Ilaria Maria Christina , Falquet Laurent , Hummler Edith , Hoogewijs David
Published: July 2022

The kidney is strongly dependent on a continuous oxygen supply, and is conversely highly sensitive to hypoxia. Controlled oxygen gradients are essential for renal control of solutes and urine-concentrating mechanisms, which also depend on various hormones including aldosterone. The cortical collecting duct (CCD) is part of the aldosterone-sensitive distal nephron and possesses a key function in fine-tuned distal salt handling. It is well known that aldosterone is consistently decreased upon hypoxia. Furthermore, a recent study reported a hypoxia-dependent down-regulation of sodium currents within CCD cells. We thus investigated the possibility that cells from the cortical collecting duct are responsive to hypoxia, using the mouse cortical collecting duct cell line mCCDcl1 as a model. By analyzing the hypoxia-dependent transcriptome of mCCDcl1 cells, we found a large number of differentially-expressed genes (3086 in total logFC< −1 or >1) following 24 h of hypoxic conditions (0.2% O2). A gene ontology analysis of the differentially-regulated pathways revealed a strong decrease in oxygen-linked processes such as ATP metabolic functions, oxidative phosphorylation, and cellular and aerobic respiration, while pathways associated with hypoxic responses were robustly increased. The most pronounced regulated genes were confirmed by RT-qPCR. The low expression levels of Epas1 under both normoxic and hypoxic conditions suggest that Hif-1α, rather than Hif-2α, mediates the hypoxic response in mCCDcl1 cells. Accordingly, we generated shRNA-mediated Hif-1α knockdown cells and found Hif-1α to be responsible for the hypoxic induction of established hypoxically-induced genes. Interestingly, we could show that following shRNA-mediated knockdown of Esrra, Hif-1α protein levels were unaffected, but the gene expression levels of Egln3 and Serpine1 were significantly reduced, indicating that Esrra might contribute to the hypoxia-mediated expression of these and possibly other genes. Collectively, mCCDcl1 cells display a broad response to hypoxia and represent an adequate cellular model to study additional factors regulating the response to hypoxia.
The Role of Polymorphisms at the Interleukin-1, Interleukin-4, GATA-3 and Cyclooxygenase-2 Genes in Non-Surgical Periodontal Therapy
Authors: Walther Kay-Arne , Gonzales José Roberto , Gröger Sabine , Ehmke Benjamin , Kaner Dogan , Lorenz Katrin , Eickholz Peter , Kocher Thomas , Kim Ti-Sun , Schlagenhauf Ulrich , Koch Raphael , Meyle Jörg
Published: July 2022

Periodontitis is a multifactorial disease. The aim of this explorative study was to investigate the role of Interleukin-(IL)-1, IL-4, GATA-3 and Cyclooxygenase-(COX)-2 polymorphisms after non-surgical periodontal therapy with adjunctive systemic antibiotics (amoxicillin/metronidazole) and subsequent maintenance in a Caucasian population. Analyses were performed using blood samples from periodontitis patients of a multi-center trial (ClinicalTrials.gov NCT00707369=ABPARO-study). Polymorphisms were analyzed using quantitative real-time PCR. Clinical attachment levels (CAL), percentage of sites showing further attachment loss (PSAL) ≥1.3 mm, bleeding on probing (BOP) and plaque score were assessed. Exploratory statistical analysis was performed. A total of 209 samples were genotyped. Patients carrying heterozygous genotypes and single-nucleotide-polymorphisms (SNP) on the GATA-3-IVS4 +1468 gene locus showed less CAL loss than patients carrying wild type. Heterozygous genotypes and SNPs on the IL-1A-889, IL-1B +3954, IL-4-34, IL-4-590, GATA-3-IVS4 +1468 and COX-2-1195 gene loci did not influence CAL. In multivariate analysis, CAL was lower in patients carrying GATA-3 heterozygous genotypes and SNPs than those carrying wild-types. For the first time, effects of different genotypes were analyzed in periodontitis progression after periodontal therapy and during supportive treatment using systemic antibiotics demonstrating a slight association of GATA-3 gene locus with CAL. This result suggests that GATA-3 genotypes are a contributory but non-essential risk factor for periodontal disease progression.
Y192 within the SH2 Domain of Lck Regulates TCR Signaling Downstream of PLC-γ1 and Thymic Selection
Authors: Kästle Matthias , Merten Camilla , Hartig Roland , Plaza-Sirvent Carlos , Schmitz Ingo , Bommhardt Ursula , Schraven Burkhart , Simeoni Luca
Published: July 2022

Signaling via the TCR, which is initiated by the Src-family tyrosine kinase Lck, is crucial for the determination of cell fates in the thymus. Because of its pivotal role, ablation of Lck results in a profound block of T-cell development. Here, we show that, in addition to its well-known function in the initiation of TCR signaling, Lck also acts at a more downstream level. This novel function of Lck is determined by the tyrosine residue (Y192) located in its SH2 domain. Thymocytes from knock-in mice expressing a phosphomimetic Y192E mutant of Lck initiate TCR signaling upon CD3 cross-linking up to the level of PLC-γ1 phosphorylation. However, the activation of downstream pathways including Ca2+ influx and phosphorylation of Erk1/2 are impaired. Accordingly, positive and negative selections are blocked in LckY192E knock-in mice. Collectively, our data indicate that Lck has a novel function downstream of PLCγ-1 in the regulation of thymocyte differentiation and selection.
Potential Renal Damage Biomarkers in Alport Syndrome—A Review of the Literature
Authors: Gomes Ana Marta , Lopes Daniela , Almeida Clara , Santos Sofia , Malheiro Jorge , Lousa Irina , Caldas Afonso Alberto , Beirão Idalina
Published: July 2022

Alport syndrome (AS) is the second most common cause of inherited chronic kidney disease. This disorder is caused by genetic variants on COL4A3, COL4A4 and COL4A5 genes. These genes encode the proteins that constitute collagen type IV of the glomerular basement membrane (GBM). The heterodimer COL4A3A4A5 constitutes the majority of the GBM, and it is essential for the normal function of the glomerular filtration barrier (GFB). Alterations in any of collagen type IV constituents cause disruption of the GMB structure, allowing leakage of red blood cells and albumin into the urine, and compromise the architecture of the GFB, inducing inflammation and fibrosis, thus resulting in kidney damage and loss of renal function. The advances in DNA sequencing technologies, such as next-generation sequencing, allow an accurate diagnose of AS. Due to the important risk of the development of progressive kidney disease in AS patients, which can be delayed or possibly prevented by timely initiation of therapy, an early diagnosis of this condition is mandatory. Conventional biomarkers such as albuminuria and serum creatinine increase relatively late in AS. A panel of biomarkers that might detect early renal damage, monitor therapy, and reflect the prognosis would have special interest in clinical practice. The aim of this systematic review is to summarize the biomarkers of renal damage in AS as described in the literature. We found that urinary Podocin and Vascular Endothelial Growth Factor A are important markers of podocyte injury. Urinary Epidermal Growth Factor has been related to tubular damage, interstitial fibrosis and rapid progression of the disease. Inflammatory markers such as Transforming Growth Factor Beta 1, High Motility Group Box 1 and Urinary Monocyte Chemoattractant Protein- 1 are also increased in AS and indicate a higher risk of kidney disease progression. Studies suggest that miRNA-21 is elevated when renal damage occurs. Novel techniques, such as proteomics and microRNAs, are promising.
The Genome of the Marine Alga Ulva compressa (Chlorophyta) Reveals Protein-Coding Genes with Similarity to Plants and Green Microalgae, but Also to Animal, Bacterial, and Fungal Genes
Authors: Osorio Héctor , Tapia-Reyes Patricio , Espinoza Daniela , Laporte Daniel , González Alberto , Castro-Nallar Eduardo , Moenne Alejandra
Published: July 2022

The genome of the marine alga Ulva compressa was assembled using long and short reads. The genome assembly was 80.8 Mb in size and encoded 19,207 protein-coding genes. Several genes encoding antioxidant enzymes and a few genes encoding enzymes that synthesize ascorbate and glutathione were identified, showing similarity to plant and bacterial enzymes. Additionally, several genes encoding signal transduction protein kinases, such as MAPKs, CDPKS, CBLPKs, and CaMKs, were also detected, showing similarity to plants, green microalgae, and bacterial proteins. Regulatory transcription factors, such as ethylene- and ABA-responsive factors, MYB, WRKY, and HSTF, were also present and showed similarity to plant and green microalgae transcription factors. Genes encoding enzymes that synthesize ACC and ABA-aldehyde were also identified, but oxidases that synthesize ethylene and ABA, as well as enzymes that synthesize other plant hormones, were absent. Interestingly, genes involved in plant cell wall synthesis and proteins related to animal extracellular matrix were also detected. Genes encoding cyclins and CDKs were also found, and CDKs showed similarity to animal and fungal CDKs. Few genes encoding voltage-dependent calcium channels and ionotropic glutamate receptors were identified as showing similarity to animal channels. Genes encoding Transient Receptor Potential (TRP) channels were not identified, even though TRPs have been experimentally detected, indicating that the genome is not yet complete. Thus, protein-coding genes present in the genome of U. compressa showed similarity to plant and green microalgae, but also to animal, bacterial, and fungal genes.
The p.Pro482Ala Variant in the CNNM2 Gene Causes Severe Hypomagnesemia Amenable to Treatment with Spironolactone
Authors: Petrakis Ioannis , Drosataki Eleni , Stavrakaki Ioanna , Dermitzaki Kleio , Lygerou Dimitra , Konidaki Myrto , Pleros Christos , Kroustalakis Nikolaos , Maragkou Sevasti , Androvitsanea Ariadni , Stylianou Ioannis , Zaganas Ioannis , Stylianou Kostas
Published: July 2022

Renal hypomagnesemia syndromes involving CNNM2 protein pathogenic variants are associated with variable degrees of neurocognitive dysfunction and hypomagnesemia. Here, we report a family with a novel CNNM2 p.Pro482Ala variant, presenting with overt hypomagnesemia and mild neurological involvement (autosomal dominant renal hypomagnesemia 6, HOMG6, MIM# 613882). Using a bioinformatics approach, we showed that the p.Pro482Ala amino acid substitution causes a 3D conformational change in CNNM2 structure in the cystathionin beta synthase (CBS) domain and the carboxy-terminal protein segment. A novel finding was that aldosterone inhibition with spironolactone helped to alleviate hypomagnesemia and symptoms in the proband.
Hematopoietic Stem and Progenitor Cells (HSPCs) and Hematopoietic Microenvironment: Molecular and Bioinformatic Studies of the Zebrafish Models
Authors: Faisal Muhammad , Hassan Mubashir , Kumar Aman , Zubair Muhammad , Jamal Muhammad , Menghwar Harish , Saad Muhammad , Kloczkowski Andrzej
Published: July 2022

Hematopoietic stem cells (HSCs) reside in a specialized microenvironment in a peculiar anatomic location which regulates the maintenance of stem cells and controls its functions. Recent scientific progress in experimental technologies have enabled the specific detection of epigenetic factors responsible for the maintenance and quiescence of the hematopoietic niche, which has improved our knowledge of regulatory mechanisms. The aberrant role of RNA-binding proteins and their impact on the disruption of stem cell biology have been reported by a number of recent studies. Despite recent modernization in hematopoietic microenvironment research avenues, our comprehension of the signaling mechanisms and interactive pathways responsible for integration of the hematopoietic niche is still limited. In the past few decades, zebrafish usage with regards to exploratory studies of the hematopoietic niche has expanded our knowledge for deeper understanding of novel cellular interactions. This review provides an update on the functional roles of different genetic and epigenetic factors and molecular signaling events at different sections of the hematopoietic microenvironment. The explorations of different molecular approaches and interventions of latest web-based tools being used are also outlined. This will help us to get more mechanistic insights and develop therapeutic options for the malignancies.
Noncatalytic Domains in DNA Glycosylases
Authors: Torgasheva Natalia A. , Diatlova Evgeniia A. , Grin Inga R. , Endutkin Anton V. , Mechetin Grigory V. , Vokhtantsev Ivan P. , Yudkina Anna V. , Zharkov Dmitry O.
Published: July 2022

Many proteins consist of two or more structural domains: separate parts that have a defined structure and function. For example, in enzymes, the catalytic activity is often localized in a core fragment, while other domains or disordered parts of the same protein participate in a number of regulatory processes. This situation is often observed in many DNA glycosylases, the proteins that remove damaged nucleobases thus initiating base excision DNA repair. This review covers the present knowledge about the functions and evolution of such noncatalytic parts in DNA glycosylases, mostly concerned with the human enzymes but also considering some unique members of this group coming from plants and prokaryotes.
Beta 2-Adrenergic Receptor in Circulating Cancer-Associated Cells Predicts for Increases in Stromal Macrophages in Circulation and Patient Survival in Metastatic Breast Cancer
Authors: Gardner Kirby P. , Cristofanilli Massimo , Chumsri Saranya , Lapidus Rena , Tang Cha-Mei , Raghavakaimal Ashvathi , Adams Daniel L.
Published: July 2022

The usage of beta blockers in breast cancer (BC) patients is implicated in the reduction in distant metastases, cancer recurrence, and cancer mortality. Studies suggest that the adrenergic pathway is directly involved in sympathetic-driven hematopoietic activation of pro-tumor microenvironmental proliferation and tumor cell trafficking into the circulation. Cancer-associated macrophage-like cells (CAMLs) are pro-tumor polynucleated monocytic cells of hematopoietic origin emanating from tumors which may aid in circulating tumor cell (CTC) dissemination into the circulation. We examined the linkage between Beta-2 adrenergic receptor (B2AR) signaling in CAMLs and CTCs by establishing expression profiles in a model BC cell line (MDA-MB-231). We compared the model to CAMLs and CTCs found in patents. Although internalization events were observed in patients, differences were found in the expression of B2AR between the tumor cell lines and the CAMLs found in patients. High B2AR expression on patients’ CAMLs was correlated with significantly more CAMLs in the circulation (p = 0.0093), but CTCs had no numerical relationship (p = 0.1565). High B2AR CAML expression was also significantly associated with a larger size of CAMLs (p = 0.0073), as well as being significantly associated with shorter progression-free survival (p = 0.0097) and overall survival (p = 0.0265). These data suggest that B2AR expression on CAMLs is closely related to the activation, intravasation, and growth of CAMLs in the circulation.
Comparative Use of Contralateral and Sham-Operated Controls Reveals Traces of a Bilateral Genetic Response in the Rat Brain after Focal Stroke
Authors: Filippenkov Ivan B. , Remizova Julia A. , Denisova Alina E. , Stavchansky Vasily V. , Golovina Ksenia D. , Gubsky Leonid V. , Limborska Svetlana A. , Dergunova Lyudmila V.
Published: July 2022

Ischemic stroke is a multifactorial disease with a complex etiology and global consequences. Model animals are widely used in stroke studies. Various controls, either brain samples from sham-operated (SO) animals or symmetrically located brain samples from the opposite (contralateral) hemisphere (CH), are often used to analyze the processes in the damaged (ipsilateral) hemisphere (IH) after focal stroke. However, previously, it was shown that focal ischemia can lead to metabolic and transcriptomic changes not only in the IH but also in the CH. Here, using a transient middle cerebral artery occlusion (tMCAO) model and genome-wide RNA sequencing, we identified 1941 overlapping differentially expressed genes (DEGs) with a cutoff value >1.5 and Padj < 0.05 that reflected the general transcriptome response of IH subcortical cells at 24 h after tMCAO using both SO and CH controls. Concomitantly, 861 genes were differentially expressed in IH vs. SO, whereas they were not vs. the CH control. Furthermore, they were associated with apoptosis, the cell cycle, and neurotransmitter responses. In turn, we identified 221 DEGs in IH vs. CH, which were non-DEGs vs. the SO control. Moreover, they were predominantly associated with immune-related response. We believe that both sets of non-overlapping genes recorded transcriptome changes in IH cells associated with transhemispheric differences after focal cerebral ischemia. Thus, the specific response of the CH transcriptome should be considered when using it as a control in studies of target brain regions in diseases that induce a global bilateral genetic response, such as stroke.
Fluorescent Phase-Changing Perfluorocarbon Nanodroplets as Activatable Near-Infrared Probes
Authors: Spatarelu Catalina-Paula , Van Namen Austin , Jandhyala Sidhartha , Luke Geoffrey P.
Published: July 2022

The sensitivity of fluorescence imaging is limited by the high optical scattering of tissue. One approach to improve sensitivity to small signals is to use a contrast agent with a signal that can be externally modulated. In this work, we present a new phase-changing perfluorocarbon nanodroplet contrast agent loaded with DiR dye. The nanodroplets undergo a liquid-to-gas phase transition when exposed to an externally applied laser pulse. This results in the unquenching of the encapsulated dye, thus increasing the fluorescent signal, a phenomenon that can be characterized by an ON/OFF ratio between the fluorescence of activated and nonactivated nanodroplets, respectively. We investigate and optimize the quenching/unquenching of DiR upon nanodroplets’ vaporization in suspension, tissue-mimicking phantoms and a subcutaneous injection mouse model. We also demonstrate that the vaporized nanodroplets produce ultrasound contrast, enabling multimodal imaging. This work shows that these nanodroplets could be applied to imaging applications where high sensitivity is required.
Gal-3BP in Viral Infections: An Emerging Role in Severe Acute Respiratory Syndrome Coronavirus 2
Authors: Gallo Valentina , Arienzo Alyexandra , Iacobelli Stefano , Iacobelli Valentina , Antonini Giovanni
Published: July 2022

Galectin-3 binding protein (Gal-3BP) is a multifunctional glycoprotein involved in cell–cell and cell–matrix interactions known to be upregulated in cancer and various viral infections, including HIV-1, HCV, and SARS-CoV-2, with a key role in regulating the antiviral immune response. Studies have identified a direct correlation between circulating levels of Gal-3BP and the severity of disease and/or disease progression for some viral infections, including SARS-CoV-2, suggesting a role of Gal-3BP in these processes. Due to Gal-3BP’s complex biology, the molecular mechanisms underlying its role in viral diseases have been only partially clarified. Gal-3BP induces the expression of interferons (IFNs) and proinflammatory cytokines, including interleukin-6 (IL-6), mainly interacting with galectin-3, targeting the TNF receptor-associated factors (TRAF-6 and TRAF-3) complex, thus having a putative role in the modulation of TGF-β signaling. In addition, an antiviral activity of Gal-3BP has been ascribed to a direct interaction of the protein with virus components. In this review, we explored the role of Gal-3BP in viral infections and the relationship between Gal-3BP upregulation and disease severity and progression, mainly focusing on SARS-CoV-2. Augmented knowledge of Gal-3BP’s role in virus infections can be useful to evaluate its possible use as a prognostic biomarker and as a putative target to block or attenuate severe disease.
Partial Endothelial Nitric Oxide Synthase Deficiency Exacerbates Cognitive Deficit and Amyloid Pathology in the APPswe/PS1ΔE9 Mouse Model of Alzheimer’s Disease
Authors: Ahmed Sara , Jing Yu , Mockett Bruce G. , Zhang Hu , Abraham Wickliffe C. , Liu Ping
Published: July 2022

Increasing evidence implicates endothelial dysfunction in the pathogenesis of Alzheimer’s disease (AD). Nitric oxide (NO) derived from endothelial NO synthase (eNOS) is essential in maintaining cerebrovascular function and can modulate the production and clearance of amyloid beta (Aβ). APPswe/PSdE1 (APP/PS1) mice display age-related Aβ accumulation and memory deficits. In order to make the model more clinically relevant with an element of endothelial dysfunction, we generated APP/PS1/eNOS+/− mice by crossing complete eNOS deficient (eNOS−/−) mice and APP/PS1 mice. APP/PS1/eNOS+/− mice at 8 months of age displayed a more severe spatial working memory deficit relative to age-matched APP/PS1 mice. Moreover, immunohistochemistry and immunoblotting revealed significantly increased Aβ plaque load in the brains of APP/PS1/eNOS+/− mice, concomitant with upregulated BACE-1 (hence increased Aβ production), downregulated insulin-degrading enzyme (hence reduced Aβ clearance) and increased immunoreactivity and expression of microglia. The present study, for the first time, demonstrated that partial eNOS deficiency exacerbated behavioral dysfunction, Aβ brain deposition, and microglial pathology in APP/PS1 mice, further implicating endothelial dysfunction in the pathogenesis of AD. The present findings also provide the scientific basis for developing preventive and/or therapeutic strategies by targeting endothelial dysfunction.