bluuebunny/crossref_metadata_2025 huggingface dataset:
Self-Reported Eating Speed Is Associated with Indicators of Obesity in Adults: A Systematic Review and Meta-Analysis
Authors: Kolay Ezgi , Bykowska-Derda Aleksandra , Abdulsamad Safa , Kaluzna Malgorzata , Samarzewska Karolina , Ruchala Marek , Czlapka-Matyasik Magdalena
Published: November 2021

Eating speed (ES) as a dietary behaviour has become a widely discussed factor for weight management and obesity. This study analysed the relationship between ES and anthropometric indicators of obesity, including BMI and waist circumference (WC) in adults. A search conducted of PubMed, Web of Science, Science Direct and Scopus found six longitudinal studies and fifteen cross-sectional studies published for further analysis. A quality assessment was performed with the MINORS checklist. Eight studies were included in the meta-analysis and almost all reviewed studies showed that ES was associated with BMI, and non-fast eaters had significantly lower BMI than fast eaters. Therefore, it was assumed that slowing down the ES may be an effective strategy for weight management and lowering obesity risk. There was also an association between WC and ES. Assessment of eating speed can be included in nutrition surveys to analyse obesity risk. More broadly, research is also needed to establish a validated and standardised methodology to determine eating speed. Further research needs to examine the links between eating speed, obesity, ethnicity, sex, food culture and chronic diseases.
On the Biochemical and Physiological Responses of ‘Crimson Seedless’ Grapes Coated with an Edible Composite of Pectin, Polyphenylene Alcohol, and Salicylic Acid
Authors: Lo’ay A. A. , Rabie M. M. , Alhaithloul Haifa A. S. , Alghanem Suliman M. S. , Ibrahim Aly M. , Abdein Mohamed A. , Abdelgawad Zinab A.
Published: November 2021

The ‘Crimson seedless’ grape encountered several difficulties during shelf life, including weight loss, rachis browning, and berry shattering. The effect of exogenous pectin (PE) and polyphenol alcohol (PVA) with supporting salicylic acid (SA) at different concentrations (0, 1, and 2 mM) was applied. The coating was applied to bunches for 5 min and stored at room temperature (26 ± 1 °C and RH 65 ± 3%) for 4 days. In this study, postharvest application of PE + PVA-SA can significantly reduce the cell wall degradation enzyme activities of ‘Crimson seedless’ grape during shelf life. ‘Crimson seedless’ bunches, treated with PE + PVA-SA 2 mmol L−1, had a lowered rachis browning index (RB index), weight loss (WL%), and berry shattering percentage (BS%) and preserved berry color hue angle (ho) compared to untreated bunches during shelf-life duration. Moreover, the PE + PVA-SA 2 mM improved berry firmness (BF) and removal force (BRF). It also improved the soluble solid content (SSC%), titratable acidity (TA%), and SSC: TA-ratio, for assessing berry maturity. The cellular metabolism enzyme activities (CMEAs) of the cell wall such as polygalacturonase (PG), cellulase (CEL), xylanase (XYL), and pectinase (PT) were minimized by applying PE + PVA-SA 2 mM coatings throughout storage duration. The accumulation of malondialdehyde (MDA) and cell wall damage, as well as the electrolyte leakage percentage (EL%), was reduced. PE + PVA-SA 2 mM maintained DPPH radical quenching activities and minimized O2− and H2O2 production rates. Collectively, these findings suggest that PE + PVA with the presence of SA as a coating treatment preserved ‘Crimson seedless’ bunches during shelf life. PE + PVA-SA 2 mM might be at least partially ascribed to the enhancement of bunches’ quality traits as well as inhibiting cell wall damage during the shelf-life period.
The Role of Twitter in the WHO’s Fight against the Infodemic
Authors: Muñoz-Sastre Daniel , Rodrigo-Martín Luis , Rodrigo-Martín Isabel
Published: November 2021

The COVID-19 pandemic has far-reaching consequences in various fields. In addition to its health and economic impact, there are also social, cultural and informational impacts. Regarding the latter, the World Health Organization (WHO) flagged concerns about the infodemic at the beginning of 2020. The main objective of this paper is to explore how the WHO uses its Twitter profile to inform the population on vaccines against the coronavirus, thus preventing or mitigating misleading or false information both in the media and on social networks. This study analyzed 849 vaccine-related tweets posted by the WHO on its Twitter account from 9 November 2020 (when the 73rd World Health Assembly resumed) to 14 March 2021 (three months after the start of vaccination). In order to understand the data collected, these results were compared with the actions carried out by the WHO and with the information and debates throughout this period. The analysis shows that the WHO is decidedly committed to the use of these tools as a means to disseminate messages that provide the population with accurate and scientific information, as well as to combat mis- and disinformation about the SARS-CoV-2 vaccination process.
Regional Differentiation and Influencing Factor Analysis of Residents’ Psychological Status during the Early Stage of the COVID-19 Pandemic in South China
Authors: Cheng Yeqing , Chen Yan , Xue Bing , Zhang Jinping
Published: November 2021

A scientific understanding of the impact of COVID-19 on the psychological status of residents is important for improving medical services and responding to public health emergencies. With the help of some of the most popular network communication tools (including Wechat and Weiboand QQ), online questionnaires were completed by South China citizens during the early stage of the COVID-19 pandemic based on psychological stress theory and using a comprehensive sampling method. Through cooperation with experts from other institutions, the content of the questionnaire was designed to include interviewees’ spatial locations and individual information, identify whether negative emotions were generated, and determine the level of psychological stress and the degree of perception change, etc. According to the data type, mathematical statistics and multiple logistic regression methods were used to examine regional differentiation and influencing factors regarding the psychological stress of residents using 1668 valid questionnaires from 53 municipal administrative units in South China. The results firstly showed that over the whole area there was typical regional differentiation in South China, especially in relation to negative expression and psychological stress, with this feature reflecting the dual urban–rural structure. Secondly, regional differences were obvious. Residents of Hainan showed stronger change of psychological stress than those of the other two provinces. In contrast, Guangdong residents were the least psychological stress, and the concept of a harmonious relationship between human beings and nature was not accepted as well as in the other two provinces. Thirdly, in each province the capital city acted as the regional pole, with greater psychological status. This polarization effect decreased with greater distance, reflecting the theory of growth poles in human geography. Fourthly, gender, education level, occupation, informational correction, and the possibility of infection were notable factors that affected the psychological status of interviewees facing COVID-19. However, the functions were different and were decided by the dependent variable. Lastly, based on conclusions summarized from three perspectives, it was found that regional differentiation, public information, and social structure need to focused upon in order to handle sudden major health issues.
The Magnitude and Directions of the Associations between Early Life Factors and Metabolic Syndrome Differ across Geographical Locations among Migrant and Non-Migrant Ghanaians—The RODAM Study
Authors: van der Heijden Thijs G. W. , Chilunga Felix P. , Meeks Karlijn A. C. , Addo Juliet , Danquah Ina , Beune Erik J. , Bahendeka Silver K. , Klipstein-Grobusch Kerstin , Mockenhaupt Frank P. , Waltz Mitzi M. , Agyemang Charles
Published: November 2021

Background: Early-life factors (ELFs) such as childhood nutrition and childhood socio-economic status could be the drivers of the increase in metabolic syndrome (MetSyn) among African populations, but data are lacking. This study evaluated whether markers of childhood nutritional status and childhood socio-economic status were associated with MetSyn in adulthood among migrant Ghanaians living in Europe and non-migrant Ghanaians living in Ghana. Methods: Data from the Research on Obesity and Diabetes among African Migrants (RODAM) study, involving 2008 migrants and 2320 non-migrants aged ≥25 years, were analysed for this study. We used leg-length to height ratio (LHR), which is an anthropometric marker of childhood nutritional status, and parental education, which is a marker of childhood socio-economic status, as proxies. Adjusted odds ratios (AOR) and 95% confidence intervals (95% CI) were calculated by logistic regression with adjustments for demographic and lifestyle factors. Results: Parental education was higher among Ghanaians in Europe than among residents in rural and urban Ghana. The prevalence of MetSyn was 18.5%, 27.7% and 33.5% for rural, urban, and migrant residents, respectively. LHR was inversely associated with MetSyn among migrants. Compared with high paternal education, individuals with low paternal education had lower odds of MetSyn in migrants (AOR 0.71 95% CI 0.54–0.94). In contrast, compared with high maternal education, individuals with intermediate maternal education had higher odds of MetSyn in urban Ghanaians (AOR 4.53 95% CI 1.50–3.74). No associations were found among rural Ghanaians. Conclusion: The magnitude and direction of the associations between ELFs and MetSyn differ across geographical locations. Intermediate maternal education was positively associated with MetSyn among urban Ghanaians, while LHR and low paternal education were inversely associated with MetSyn among migrant Ghanaians. Further research into the interplay of genetics, environment and behaviour is needed to elucidate the underlying pathological mechanisms of MetSyn amongst migrants.
Scar Tissue after a Cesarean Section—The Management of Different Complications in Pregnant Women
Authors: Stupak Aleksandra , Kondracka Adrianna , Fronczek Agnieszka , Kwaśniewska Anna
Published: November 2021

The definition of a cesarean scar pregnancy (CSP) is the localization of the gestational sac (GS) in the cicatrix tissue, which is created in the front wall of the uterus after a previous cesarean section (CS). The worldwide prevalence of CSP has been growing rapidly. However, there are no general recommendations regarding prophylaxis and treatment of the abnormalities of the anterior wall of the uterus discovered in a non-pregnant myometrium, or how to deal with existing cases of CSP. We present the latest knowledge, a holistic approach to the biology, histology, imaging, and management concerning post-CS scars based on our cases, which were treated in the Department of Pregnancy and Pathology of Pregnancy in the Medical University of Lublin, Poland. In our study, we present images of tissue samples of areas with a cicatrix in the uterus, and ultrasound and MRI images of CSP. We discuss the advances in the biology of the post-CS scar tissue, the prevention techniques used to repair the scar defect (niche) before the pregnancy, and the treatment of different complications of CSP, such as the rupture of the gravid uterus or the dehiscence of the myometrium.
Assessment of Trace Elements Supply in Canned Tuna Fish Commercialized for Human Consumption in Brazil
Authors: de Lima Nayara Vieira , Granja Arakaki Daniela , Melo Elaine Silva de Pádua , Machate David Johane , do Nascimento Valter Aragão
Published: November 2021

This study evaluates the elemental content in 4 types of canned tuna fish groups, each with 4 brands that are commercialized for human consumption in Brazil. The results are based on trace elements in canned tuna fish quantified by ICP OES and a comparison to limit levels set by the FAO/WHO. We also checked the carcinogenic risk (CR), non-carcinogenic risk (Hazard Index (HI) and Hazard Quotient (HQ)), and pollution index (PI) for the studied canned tuna samples. As and Se concentrations in all groups are above the intake values set by FAO/WHO considering specific groups. The carcinogenic risk values for arsenic (As) in groups are considerably unacceptable (≥10−4). Hazard quotients (HQ) were >1 for As in all groups, while no sample was below 1 for HI. The pollution index (PI) results show that the main canned tuna fish contaminant is aluminum, then selenium and arsenic, respectively. Only half of the samples did not present elemental contaminant levels. All studied brands of canned tuna presented elemental concentrations that could pose a health risk to human consumption, that could be from CR, HQ, HI, or PI. The contaminant levels are alarming and should raise a red flag for the intake of these products, especially a long-term one. These results urge the authorities to supervise and enforce better practices for this type of food, protecting their population from health hazards.
Environmental Pyrethroid Exposure and Cognitive Dysfunction in U.S. Older Adults: The NHANES 2001–2002
Authors: Kim Ui-Jin , Hong Myeongjin , Choi Yoon-Hyeong
Published: November 2021

Pyrethroid compounds are widely used in household insecticides and agricultural pesticides. Recent studies, however, report that pyrethroid exposures affect neurobehavioral function in animals and may be associated with adverse neurocognitive development in children. This study aimed to examine the association between pyrethroid exposure and cognitive dysfunction in older adults using a well-defined general population. We analyzed data from 336 individuals, aged 60–84 years, who participated in the National Health and Nutrition Examination Survey 2001–2002. We used urinary 3-phenoxybenzoic acid (3-PBA) concentration as a biomarker of pyrethroid exposures and assessed cognitive function with the digit–symbol coding test. The geometric means (±geometric standard errors) of creatinine-uncorrected and corrected urinary 3-PBA were 0.30 (±0.87) μg/L and 0.36 (±0.89) μg/g. After adjusting for sociodemographic factors, higher 3-PBA concentrations (> vs. ≤0.30 μg/g creatinine (median)) were associated with lower scores of cognitive function (−3.83 95% confidence interval: −7.11, −0.54). Significance was persistent after additionally adjusting for physical activity and smoking pack-year (−3.76 95% CI: −7.16, −0.36) and further adjusting for BMI and presence of hypertension and diabetes (−3.82 95% CI: −6.92, −0.71). Our findings suggest that pyrethroid exposure is associated with cognitive dysfunction in older adults.
Integrating Spatial Modelling and Space–Time Pattern Mining Analytics for Vector Disease-Related Health Perspectives: A Case of Dengue Fever in Pakistan
Authors: Naqvi Syed Ali Asad , Sajjad Muhammad , Waseem Liaqat Ali , Khalid Shoaib , Shaikh Saima , Kazmi Syed Jamil Hasan
Published: November 2021

The spatial–temporal assessment of vector diseases is imperative to design effective action plans and establish preventive strategies. Therefore, such assessments have potential public health planning-related implications. In this context, we here propose an integrated spatial disease evaluation (I-SpaDE) framework. The I-SpaDE integrates various techniques such as the Kernel Density Estimation, the Optimized Hot Spot Analysis, space–time assessment and prediction, and the Geographically Weighted Regression (GWR). It makes it possible to systematically assess the disease concentrations, patterns/trends, clustering, prediction dynamics, and spatially varying relationships between disease and different associated factors. To demonstrate the applicability and effectiveness of the I-SpaDE, we apply it in the second largest city of Pakistan, namely Lahore, using Dengue Fever (DF) during 2007–2016 as an example vector disease. The most significant clustering is evident during the years 2007–2008, 2010–2011, 2013, and 2016. Mostly, the clusters are found within the city’s central functional area. The prediction analysis shows an inclination of DF distribution from less to more urbanized areas. The results from the GWR show that among various socio-ecological factors, the temperature is the most significantly associated with the DF followed by vegetation and built-up area. While the results are important to understand the DF situation in the study area and have useful implications for public health planning, the proposed framework is flexible, replicable, and robust to be utilized in other similar regions, particularly in developing countries in the tropics and sub-tropics.
Fibromyalgia: Evidence for Deficits in Positive Psychology Resources. A Case-Control Study from the Al-Ándalus Project
Authors: Arrayás-Grajera Manuel Javier , Tornero-Quiñones Inmaculada , Gavilán-Carrera Blanca , Luque-Reca Octavio , Peñacoba-Puente Cecilia , Sierra-Robles Ángela , Carbonell-Baeza Ana , Estévez-López Fernando
Published: November 2021

Positive psychology is the study of positive subjective experience and individual traits. Identifying deficits in positive psychology regarding fibromyalgia may inform targets for management. Therefore, the aim of the present case–control study was to compare the levels of positive affect, negative affect, satisfaction with life, optimism and emotional repair in a large sample of women with fibromyalgia (cases) and age-matched peers without fibromyalgia (controls). This case–control study included 437 women with fibromyalgia (51.6 ± 7.1 years old) and 206 age-matched women without fibromyalgia (50.6 ± 7.2 years old). Participants self-reported their levels of (i) subjective well-being on the Positive and Negative Affect Schedule and the Satisfaction with Life Scale, (ii) dispositional optimism on the Life Orientation Test-Revised and (iii) emotional repair on the Trait Meta-Mood Scale. Women with fibromyalgia showed lower levels of positive affect, satisfaction with life, optimism and emotional repair and higher levels of negative affect. Large effect sizes were found for positive affect, negative affect and satisfaction with life (all, Cohen’s d ≥ 0.80) and small-to-moderate for emotional repair and optimism (both, Cohen’s d ≥ 0.50). Women with fibromyalgia experience deficits of positive psychology resources. Thus, developing tailored therapies for fibromyalgia focusing on reducing deficits in positive psychology resources may be of clinical interest, though this remains to be corroborated in future research.
In-Season Body Composition Effects in Professional Women Soccer Players
Authors: Oliveira Rafael , Francisco Ruben , Fernandes Renato , Martins Alexandre , Nobari Hadi , Clemente Filipe Manuel , Brito João Paulo
Published: November 2021

This study aimed to analyze anthropometric and body composition effects in professional soccer women players across the early and mid-competitive 2019/20 season. Seventeen players (age, height, body mass, and body mass index of 22.7 ± 6.3 years, 167.5 ± 5.6 cm, 60.7 ± 6.6 kg and 21.6 ± 0.2 kg/m2) from a Portuguese BPI League team participated in this study. The participants completed ≥80% of 57 training sessions and 13 matches. They were assessed at three points (before the start of the season (A1), after two months (A2), and after four months (A3)) using the following variables: body fat mass (BFM), soft lean mass (SLM), fat-free mass (FFM), intracellular water (ICW), extracellular water (ECW), total body water (TBW), and phase angle (PhA, 50 Khz), through InBody S10. Nutritional intake was determined through a questionnaire. Repeated measures ANCOVA and effect sizes (ES) were used with p < 0.05. The main results occurred between A1 and A2 for BFM (−21.7%, ES = 1.58), SLM (3.7%, ES = 1.24), FFM (4%, ES = 1.34), ICW (4.2%, ES = 1.41), TBW (3.7%, ES = 1.04). Furthermore, there were significant results between A1 and A3 for FFM (4.8%, ES = 1.51), ICW (5%, ES = 1.68), and PhA (10.4%, ES = 6.64). The results showed that the water parameters improved over time, which led to healthy hydration statuses. The training load structure provided sufficient stimulus for appropriate physical fitness development, without causing negative disturbances in the water compartments.
Instability Severity Index Score Does Not Predict the Risk of Shoulder Dislocation after a First Episode Treated Conservatively
Authors: Longo Umile Giuseppe , Papalia Rocco , Ciapini Gianluca , De Salvatore Sergio , Casciaro Carlo , Ferrari Elisa , Cosseddu Fabio , Novi Michele , Piergentili Ilaria , Parchi Paolo , Scaglione Michelangelo , Denaro Vincenzo
Published: November 2021

The first purpose of this study was to verify the association between Instability Severity Index Score (ISIS) and Recurrent Shoulder Dislocation (RSD) after a first episode treated conservatively. The second aim is to identify the risk factors associated with RSD after a primary acute shoulder anterior dislocation treated conservatively. A total of 111 patients with first traumatic anterior shoulder dislocation treated at a single trauma centre between January 2014 and March 2016 were enrolled. The main predictive variables of risk factors and the ISIS score were calculated. Among the 85 patients included, 26 cases of RSD were observed (30.6%). Considering the whole population, no significant association between ISIS and RSD were reported. Regarding other risk factors, high-risk working activities and rotator cuff injury had a significantly higher RSD risk. Sex, dominant limb, familiar history, hyperlaxity, contact or overhead sports, competitive sport, post-reduction physiokinesitherapy, return to sports activity time, Hill-Sachs lesion, bony Bankart lesion and great tuberosity fracture did not seem to influence the risk of RSD. No correlation between ISIS score and RSD in patients treated conservatively after a first episode of shoulder dislocation were reported. The only risk factors with a significant association to RSD were high-risk working activities and rotator cuff injury.
Assistive Technology during the COVID-19 Global Pandemic: The Roles of Government and Civil Society in Fulfilling the Social Contract
Authors: Mont Daniel , Layton Natasha , Puli Louise , Gupta Shivani , Manlapaz Abner , Shae Kylie , Tebbutt Emma , Calvo Irene , Sidiqy Mahpekay , Dube Kudakwashe , Kacilala Ulamila
Published: November 2021

The COVID-19 pandemic imposed significant challenges to users of assistive technology (AT). Three key issues emerged from a series of structured qualitative interviews with 35 AT users in six low- and middle-income countries. These were (1) access to information about COVID-19 and available supports and policies, (2) insufficiency of the government response to meet the needs of AT users, and (3) the response of civil society which partially offset the gap in government response. AT users noted the need for better communication, improved planning for the delivery and maintenance of AT during times of crisis, and higher-quality standards to ensure the availability of appropriate technology.
Physical Activity, Mental Health and Wellbeing during the First COVID-19 Containment in New Zealand: A Cross-Sectional Study
Authors: O’Brien Wendy J. , Badenhorst Claire E. , Draper Nick , Basu Arindam , Elliot Catherine A. , Hamlin Michael J. , Batten John , Lambrick Danielle , Faulkner James
Published: November 2021

Strategies implemented worldwide to contain COVID-19 outbreaks varied in severity across different countries, and established a new normal for work and school life (i.e., from home) for many people, reducing opportunities for physical activity. Positive relationships of physical activity with both mental and physical health are well recognised, and therefore the aim was to ascertain how New Zealand’s lockdown restrictions impacted physical activity, mental health and wellbeing. Participants (n = 4007; mean ± SD: age 46.5 ± 14.7 years, 72% female, 80.7% New Zealand European) completed (10–26 April 2020) an online amalgamated survey (Qualtrics): International Physical Activity Questionnaire: Short Form; Depression, Anxiety and Stress Scale-9; World Health Organisation-Five Well-Being Index; Stages of Change Scale. Positive dose–response relationships between physical activity levels and wellbeing scores were demonstrated for estimates that were unadjusted (moderate activity OR 3.79, CI 2.88–4.92; high activity OR 8.04, CI 6.07–10.7) and adjusted (confounding variables: age, gender, socioeconomic status, time sitting and co-morbidities) (moderate activity 1.57, CI 1.11–2.52; high activity 2.85, CI 1.97–4.14). The study results support previous research demonstrating beneficial effects of regular physical activity on mental health and wellbeing. Governments may use these results to promote meeting physical activity guidelines in order to protect mental health and wellbeing during the ongoing COVID-19 restrictions and future pandemics.
Genome-Wide Comprehensive Analysis of the GASA Gene Family in Populus
Authors: Han Shuo , Jiao Zhiyin , Niu Meng-Xue , Yu Xiao , Huang Mengbo , Liu Chao , Wang Hou-Ling , Zhou Yangyan , Mao Wei , Wang Xiaofei , Yin Weilun , Xia Xinli
Published: November 2021

Gibberellic acid-stimulated Arabidopsis (GASA) proteins, as cysteine-rich peptides (CRPs), play roles in development and reproduction and biotic and abiotic stresses. Although the GASA gene family has been identified in plants, the knowledge about GASAs in Populus euphratica, the woody model plant for studying abiotic stress, remains limited. Here, we referenced the well-sequenced Populus trichocarpa genome, and identified the GASAs in the whole genome of P. euphratica and P. trichocarpa. 21 candidate genes in P. trichocarpa and 19 candidate genes in P. euphratica were identified and categorized into three subfamilies by phylogenetic analysis. Most GASAs with signal peptides were located extracellularly. The GASA genes in Populus have experienced multiple gene duplication events, especially in the subfamily A. The evolution of the subfamily A, with the largest number of members, can be attributed to whole-genome duplication (WGD) and tandem duplication (TD). Collinearity analysis showed that WGD genes played a leading role in the evolution of GASA genes subfamily B. The expression patterns of P. trichocarpa and P. euphratica were investigated using the PlantGenIE database and the real-time quantitative PCR (qRT-PCR), respectively. GASA genes in P. trichocarpa and P. euphratica were mainly expressed in young tissues and organs, and almost rarely expressed in mature leaves. GASA genes in P. euphratica leaves were also widely involved in hormone responses and drought stress responses. GUS activity assay showed that PeuGASA15 was widely present in various organs of the plant, especially in vascular bundles, and was induced by auxin and inhibited by mannitol dramatically. In summary, this present study provides a theoretical foundation for further research on the function of GASA genes in P. euphratica.
Transcriptional Control of Apical-Basal Polarity Regulators
Authors: Rust Katja , Wodarz Andreas
Published: November 2021

Cell polarity is essential for many functions of cells and tissues including the initial establishment and subsequent maintenance of epithelial tissues, asymmetric cell division, and morphogenetic movements. Cell polarity along the apical-basal axis is controlled by three protein complexes that interact with and co-regulate each other: The Par-, Crumbs-, and Scrib-complexes. The localization and activity of the components of these complexes is predominantly controlled by protein-protein interactions and protein phosphorylation status. Increasing evidence accumulates that, besides the regulation at the protein level, the precise expression control of polarity determinants contributes substantially to cell polarity regulation. Here we review how gene expression regulation influences processes that depend on the induction, maintenance, or abolishment of cell polarity with a special focus on epithelial to mesenchymal transition and asymmetric stem cell division. We conclude that gene expression control is an important and often neglected mechanism in the control of cell polarity.
Increasing Transfection Efficiency of Lipoplexes by Modulating Complexation Solution for Transient Gene Expression
Authors: Kim Jaemun , Kim Ji Yul , Kim Hyeonkyeong , Kim Eunsil , Park Soonyong , Ryu Kyoung-Hwa , Lee Eun Gyo
Published: November 2021

Transient gene expression is a suitable tool for the production of biopharmaceutical candidates in the early stage of development and provides a simple and rapid alternative to the generation of stable cell line. In this study, an efficient transient gene expression methodology using DC-Chol/DOPE cationic liposomes and pDNA in Chinese hamster ovary suspension cells was established through screening of diverse lipoplex formation conditions. We modulated properties of both the liposome formation and pDNA solution, together called complexation solutions. Protein expression and cellular cytotoxicity were evaluated following transfection over the cell cultivation period to select the optimal complexation solution. Changes in hydrodynamic size, polydispersity index, and ζ potential of the liposomes and lipoplexes were analyzed depending on the various pH ranges of the complexation solutions using dynamic light scattering. The transfer of lipoplexes to the cytosol and their conformation were traced using fluorescence analysis until the early period of transfection. As a result, up to 1785 mg/L and 191 mg/L of human Fc protein and immunoglobulin G (bevacizumab), respectively, were successfully produced using acidic liposome formation and alkaline pDNA solutions. We expect that this lipoplex formation in acidic and alkaline complexation solutions could be an effective methodology for a promising gene delivery strategy.
The Emerging Role of Decellularized Plant-Based Scaffolds as a New Biomaterial
Authors: Harris Ashlee F. , Lacombe Jerome , Zenhausern Frederic
Published: November 2021

The decellularization of plant-based biomaterials to generate tissue-engineered substitutes or in vitro cellular models has significantly increased in recent years. These vegetal tissues can be sourced from plant leaves and stems or fruits and vegetables, making them a low-cost, accessible, and sustainable resource from which to generate three-dimensional scaffolds. Each construct is distinct, representing a wide range of architectural and mechanical properties as well as innate vasculature networks. Based on the rapid rise in interest, this review aims to detail the current state of the art and presents the future challenges and perspectives of these unique biomaterials. First, we consider the different existing decellularization techniques, including chemical, detergent-free, enzymatic, and supercritical fluid approaches that are used to generate such scaffolds and examine how these protocols can be selected based on plant cellularity. We next examine strategies for cell seeding onto the plant-derived constructs and the importance of the different functionalization methods used to assist in cell adhesion and promote cell viability. Finally, we discuss how their structural features, such as inherent vasculature, porosity, morphology, and mechanical properties (i.e., stiffness, elasticity, etc.) position plant-based scaffolds as a unique biomaterial and drive their use for specific downstream applications. The main challenges in the field are presented throughout the discussion, and future directions are proposed to help improve the development and use of vegetal constructs in biomedical research.
The Mechanism of Leptin on Inhibiting Fibrosis and Promoting Browning of White Fat by Reducing ITGA5 in Mice
Authors: Liu Yuexia , Li Yizhou , Liang Juntong , Sun Zhuwen , Wu Qiong , Liu Yongnian , Sun Chao
Published: November 2021

Leptin is a small molecule protein secreted by adipocytes, which can promote white fat browning through activating the hypothalamic nervous system and inhibiting downstream signaling pathways. Moreover, white fat browning has been proven to alleviate fat tissue fibrosis. This study explores the mechanism of leptin in regulating adipose tissue fibrosis and white fat browning. After treating mice with leptin, we screened out the recombinant integrin alpha 5 (ITGA5) through proteomics sequencing, which may play a role in adipose tissue fibrosis. Through real-time quantitative PCR (qPCR), western blotting (WB), hematoxylin-eosin (HE) staining, Masson’s trichrome, immunofluorescence, immunohistochemistry, etc., the results showed that after leptin treated adipocytes, the expression of fibrosis-related genes and ITGA5 was significantly down-regulated in adipocytes. We constructed fibrosis model through transforming growth factor-β (TGF-β) and a high-fat diet (HFD), and treated with ITGA5 overexpression vector and interference fragments. The results indicated the expression of fibrosis-related genes were significantly down-regulated after interfering with ITGA5. After treating adipocytes with wortmannin, fibrosis-related gene expression was inhibited after overexpression of ITGA5. Moreover, after injecting mice with leptin, we also found that leptin significantly up-regulated the expression of adipose tissue browning-related genes. Overall, our research shows that leptin can inhibit the activation of phosphatidylinositol 3 kinase (PI3K)-protein kinase B (AKT) signaling pathway by reducing the expression of ITGA5, which could alleviate adipose tissue fibrosis, and further promote white fat browning. Our research provides a theoretical basis for further research on the effect of leptin in fibrosis-related adipose tissue metabolism.
SDHI Fungicide Toxicity and Associated Adverse Outcome Pathways: What Can Zebrafish Tell Us?
Authors: Yanicostas Constantin , Soussi-Yanicostas Nadia
Published: November 2021

Succinate dehydrogenase inhibitor (SDHI) fungicides are increasingly used in agriculture to combat molds and fungi, two major threats to both food supply and public health. However, the essential requirement for the succinate dehydrogenase (SDH) complex—the molecular target of SDHIs—in energy metabolism for almost all extant eukaryotes and the lack of species specificity of these fungicides raise concerns about their toxicity toward off-target organisms and, more generally, toward the environment. Herein we review the current knowledge on the toxicity toward zebrafish (Brachydanio rerio) of nine commonly used SDHI fungicides: bixafen, boscalid, fluxapyroxad, flutolanil, isoflucypram, isopyrazam, penthiopyrad, sedaxane, and thifluzamide. The results indicate that these SDHIs cause multiple adverse effects in embryos, larvae/juveniles, and/or adults, sometimes at developmentally relevant concentrations. Adverse effects include developmental toxicity, cardiovascular abnormalities, liver and kidney damage, oxidative stress, energy deficits, changes in metabolism, microcephaly, axon growth defects, apoptosis, and transcriptome changes, suggesting that glycometabolism deficit, oxidative stress, and apoptosis are critical in the toxicity of most of these SDHIs. However, other adverse outcome pathways, possibly involving unsuspected molecular targets, are also suggested. Lastly, we note that because of their recent arrival on the market, the number of studies addressing the toxicity of these compounds is still scant, emphasizing the need to further investigate the toxicity of all SDHIs currently used and to identify their adverse effects and associated modes of action, both alone and in combination with other pesticides.
Diabetes and Cognitive Impairment: A Role for Glucotoxicity and Dopaminergic Dysfunction
Authors: Pignalosa Francesca Chiara , Desiderio Antonella , Mirra Paola , Nigro Cecilia , Perruolo Giuseppe , Ulianich Luca , Formisano Pietro , Beguinot Francesco , Miele Claudia , Napoli Raffaele , Fiory Francesca
Published: November 2021

Diabetes mellitus (DM) is a chronic metabolic disorder characterized by hyperglycemia, responsible for the onset of several long-term complications. Recent evidence suggests that cognitive dysfunction represents an emerging complication of DM, but the underlying molecular mechanisms are still obscure. Dopamine (DA), a neurotransmitter essentially known for its relevance in the regulation of behavior and movement, modulates cognitive function, too. Interestingly, alterations of the dopaminergic system have been observed in DM. This review aims to offer a comprehensive overview of the most relevant experimental results assessing DA’s role in cognitive function, highlighting the presence of dopaminergic dysfunction in DM and supporting a role for glucotoxicity in DM-associated dopaminergic dysfunction and cognitive impairment. Several studies confirm a role for DA in cognition both in animal models and in humans. Similarly, significant alterations of the dopaminergic system have been observed in animal models of experimental diabetes and in diabetic patients, too. Evidence is accumulating that advanced glycation end products (AGEs) and their precursor methylglyoxal (MGO) are associated with cognitive impairment and alterations of the dopaminergic system. Further research is needed to clarify the molecular mechanisms linking DM-associated dopaminergic dysfunction and cognitive impairment and to assess the deleterious impact of glucotoxicity.
Human Epidermal Zinc Concentrations after Topical Application of ZnO Nanoparticles in Sunscreens
Authors: Khabir Zahra , Holmes Amy M. , Lai Yi-Jen , Liang Liuen , Deva Anand , Polikarpov Michael A. , Roberts Michael S. , Zvyagin Andrei V.
Published: November 2021

Zinc oxide nanoparticle (ZnO NP)-based sunscreens are generally considered safe because the ZnO NPs do not penetrate through the outermost layer of the skin, the stratum corneum (SC). However, cytotoxicity of zinc ions in the viable epidermis (VE) after dissolution from ZnO NP and penetration into the VE is ill-defined. We therefore quantified the relative concentrations of endogenous and exogenous Zn using a rare stable zinc-67 isotope (67Zn) ZnO NP sunscreen applied to excised human skin and the cytotoxicity of human keratinocytes (HaCaT) using multiphoton microscopy, zinc-selective fluorescent sensing, and a laser-ablation inductively coupled plasma–mass spectrometry (LA-ICP-MS) methodology. Multiphoton microscopy with second harmonic generation imaging showed that 67ZnO NPs were retained on the surface or within the superficial layers of the SC. Zn fluorescence sensing revealed higher levels of labile and intracellular zinc in both the SC and VE relative to untreated skin, confirming that dissolved zinc species permeated across the SC into the VE as ionic Zn and significantly not as ZnO NPs. Importantly, the LA-ICP-MS estimated exogenous 67Zn concentrations in the VE of 1.0 ± 0.3 μg/mL are much lower than that estimated for endogenous VE zinc of 4.3 ± 0.7 μg/mL. Furthermore, their combined total zinc concentrations in the VE are much lower than the exogenous zinc concentration of 21 to 31 μg/mL causing VE cytotoxicity, as defined by the half-maximal inhibitory concentration of exogenous 67Zn found in human keratinocytes (HaCaT). This speaks strongly for the safety of ZnO NP sunscreens applied to intact human skin and the associated recent US FDA guidance.
Implementation of Hospital-Based Supplemental Duchenne Muscular Dystrophy Newborn Screening (sDMDNBS): A Pathway to Broadening Adoption
Authors: Parad Richard B. , Sheldon Yvonne , Bhattacharjee Arindam
Published: November 2021

Duchenne muscular dystrophy (DMD) is not currently part of mandatory newborn screening, despite the availability of a test since 1975. In the absence of screening, a DMD diagnosis is often not established in patients until 3–6 years of age. During this time, irreversible muscle degeneration takes place, and clinicians agree that the earlier therapy is initiated, the better the long-term outcome. With recent availability of FDA-approved DMD therapies, interest has renewed for adoption by state public health programs, but such implementation is a multiyear process. To speed access to approved therapies, we implemented a unique, hospital-based program offering parents of newborns an optional, supplemental DMD newborn screen (NBS) via a two-tiered approach: utilizing a creatine kinase (CK) enzyme assay coupled with rapid targeted next-generation sequencing (tNGS) for the DMD gene (using a Whole-Exome Sequencing (WES) assay). The tNGS/WES assay integrates the ability to detect both point mutations and large deletion/duplication events. This tiered newborn screening approach allows for the opportunity to improve treatment and outcomes, avoid the diagnostic delays, and diminish healthcare disparities. To implement this screening algorithm through hospitals in a way that would ultimately be acceptable to public health laboratories, we chose an FDA-approved CK-MM immunoassay to avoid the risks of false-negative/-positive results. Because newborn CK values can be affected due to non-DMD-related causes such as birth trauma, a confirmatory repeat CK assay on a later dried blood spot (DBS) collection has been proposed. Difficulties associated with non-routine repeat DBS collection, including the tracking and recall of families, and the potential creation of parental anxiety associated with false-positive results, can be avoided with this algorithm. Whereas a DMD diagnosis is essentially ruled out by the absence of detected DMD sequence abnormalities, a subsequent CK would still be warranted to confirm resolution of the initial elevation, and thus the absence of non-DMD muscular dystrophy or other pathologies. To date, we have screened over 1500 newborns (uptake rate of ~80%) by a CK-MM assay, and reflexed DMD tNGS in 29 of those babies. We expect the experience from this screening effort will serve as a model that will allow further expansion to other hospital systems until a universal public health screening is established.
Help Me Learn! Architecture and Strategies to Combine Recommendations and Active Learning in Manufacturing
Authors: Zajec Patrik , Rožanec Jože M. , Trajkova Elena , Novalija Inna , Kenda Klemen , Fortuna Blaž , Mladenić Dunja
Published: November 2021

This research work describes an architecture for building a system that guides a user from a forecast generated by a machine learning model through a sequence of decision-making steps. The system is demonstrated in a manufacturing demand forecasting use case and can be extended to other domains. In addition, the system provides the means for knowledge acquisition by gathering data from users. Finally, it implements an active learning component and compares multiple strategies to recommend media news to the user. We compare such strategies through a set of experiments to understand how they balance learning and provide accurate media news recommendations to the user. The media news aims to provide additional context to demand forecasts and enhance judgment on decision-making.
Diabetes Mellitus in Prader-Willi Syndrome: Natural History during the Transition from Childhood to Adulthood in a Cohort of 39 Patients
Authors: Clerc Alice , Coupaye Muriel , Mosbah Héléna , Pinto Graziella , Laurier Virginie , Mourre Fabien , Merrien Christine , Diene Gwenaëlle , Poitou Christine , Tauber Maithé
Published: November 2021

Type 2 diabetes mellitus (T2DM) affects 20% of patients with Prader-Willi syndrome (PWS), with many cases diagnosed during the transition period. Our aim was to describe the natural history of T2DM in patients with PWS before the age of 25 years and to develop screening and preventive strategies. Thirty-nine patients followed in the French PWS Reference Center were included (median age 25.6 years [23.7; 31.7]). Twenty-one had been treated with growth hormone (GH), fifteen had not, and three had an unknown status. The median age at T2DM diagnosis was 16.8 years (11–24) and the median BMI was 39 kg/m2 [34.6; 45], with 34/35 patients living with obesity. The patients displayed frequent psychiatric (48.3% hospitalization,) and metabolic (56.4% hypertriglyceridemia,) comorbidities and a parental history of T2DM (35.7%) or overweight (53.6%) compared to the PWS general population. There was no difference in BMI and metabolic complications between the GH-treated and non-GH-treated groups at T2DM diagnosis. Patients with PWS who develop early T2DM have severe obesity, a high frequency of psychiatric and metabolic disorders, and a family history of T2DM and overweight. These results underline the need for early identification of patients at risk, prevention of obesity, and repeated blood glucose monitoring during the transition period.
Levels of Biosimilar Infliximab during and after Induction Treatment in Crohn’s Disease and Ulcerative Colitis—A Prospective Polish Population Study
Authors: Pękala Anna , Filip Rafał
Published: November 2021

Background: Primary lack or secondary loss of response to therapy with infliximab is a significant problem. This study aimed to evaluate the response to treatment in patients with Crohn’s disease (CD) and ulcerative colitis (UC) achieving therapeutic and sub-therapeutic trough levels of biosimilar infliximab (CT-P13). Results: A total of 65 patients (32 with CD and 33 with UC) were recruited. The overall response rate in both CD and UC patients exceeded 80%. There were no significant differences in treatment response and CT-P13 levels for patients with CD or UC. We did not find significant differences in the percentage of patients achieving drug levels of 3 μg/mL at week 6, 10, or 12; a significant decrease was observed at week 14. Up to 55.5% of patients with CD and 64.3% of patients with UC with sub-therapeutic CT-P13 levels at week 14 primarily responded to treatment. Conclusions: Intermediate measurements of drug levels at weeks 10 and 12 did not capture any pronounced decrease in infliximab concentrations below therapeutic levels in either group, thus suggesting no clinical usefulness. A significant percentage of patients primarily responded to treatment despite sub-therapeutic drug levels after the induction phase.
The Correlation between Lower Extremity Fracture and Subsequent Arterial Embolism and Thrombosis—A National Population Cohort Study
Authors: Chen Jian-Xun , Hsu Shao-Yun , Lin Mei-Chen , Shih Pin-Keng
Published: November 2021

The hazard of subsequent arterial embolism and thrombosis (SAET) in patients with lower leg fractures is not yet well demonstrated. The purpose of this study is to determine the correlation between lower leg fracture and SAET in Taiwan. A total of 134,844 patients with lower leg fractures (ICD-9-CM: 823) and chronological diagnosis as SAET (ICD-9-CM: 444.22) was matched (1:1) to the non-fracture cohort according to their propensity score (data coming from the National Health Insurance database between January 2000 to December 2012). Patients were matched by age, gender, and comorbidities. The incidence of SAET and correlation between SAET development and lower leg fracture was statistically analyzed, and subgroup analysis categorized by characteristics and comorbidities was conducted as well. The cumulative incidence of SAET was calculated by Kaplan–Meier analysis. Kaplan–Meier analysis plot showed that, by the end of the ten-year follow-up period, the cumulative incidence of SAET was significantly higher for the lower leg fracture cohort than for the non-fracture cohort (log-rank test: p < 0.001). The lower leg fracture, male, elder age (45–64-year-old; ≥65-year-old), hypertension, diabetes mellitus, and gout were significantly associated with lower extremity SAET risk compared with the matched group. There was an inseparable correlation between the lower leg fracture group and the risks of SAET; subgroup analysis by gender (male, female), age (age < 40 years, age 40–64 years, and age > 65 years) and comorbidities (hypertension, diabetes mellitus, and gout) show compatible results as well. Patients with lower leg fracture have a significantly increased risk of SAET since then two years after the fracture. The hazard of SAET was significantly higher in patients with lower leg fracture than in the non-fracture cohort, and the high incidence was found since then two years after fracture. Further studies are warranted.