bluuebunny/crossref_metadata_2025 huggingface dataset:
Treacher Collins Syndrome: Genetics, Clinical Features and Management
Authors: Marszałek-Kruk Bożena Anna , Wójcicki Piotr , Dowgierd Krzysztof , Śmigiel Robert
Published: September 2021

Treacher Collins syndrome (TCS) is associated with abnormal differentiation of the first and second pharyngeal arches, occurring during fetal development. Features of TCS include microtia with conductive hearing loss, slanting palpebral fissures with possibly coloboma of the lateral part of lower eyelids, midface hypoplasia, micrognathia as well as sporadically cleft palate and choanal atresia or stenosis. TCS occurs in the general population at a frequency of 1 in 50,000 live births. Four subtypes of Treacher Collins syndrome exist. TCS can be caused by pathogenic variants in the TCOF1, POLR1D, POLR1C and POLR1B genes. Genetically, the TCOF1 gene contains 27 exons which encodes the Treacle protein. In TCOF1, over 200 pathogenic variants have been identified, of which most are deletions leading to a frame-shift, that result in the formation of a termination codon. In the presented article, we review the genetics and phenotype of TCS as well as the management and surgical procedures utilized for treatment.
Healthcare Quality Improvement Analytics: An Example Using Computerized Provider Order Entry
Authors: Cho Jungwon , Shin Sangmi , Jeong Youngmi , Lee Eunsook , Ahn Soyeon , Won Seunghyun , Lee Euni
Published: September 2021

Evaluation of sustainability after quality improvement (QI) projects in healthcare settings is an essential part of monitoring and future QI planning. With limitations in adopting quasi-experimental study design in real-world practice, healthcare professionals find it challenging to present the sustained effect of QI changes effectively. To provide quantitative methodological approaches for demonstrating the sustainability of QI projects for healthcare professionals, we conducted data analyses based on a QI project to improve the computerized provider order entry system to reduce patients’ dosing frequencies in Korea. Data were collected for 5 years: 24-month pre-intervention, 12-month intervention, and 24-month post-intervention. Then, analytic approaches including control chart, Analysis of Variance (ANOVA), and segmented regression were performed. The control chart intuitively displayed how the outcomes changed over the entire period, and ANOVA was used to test whether the outcomes differed between groups. Last, segmented regression analysis was conducted to evaluate longitudinal effects of interventions over time. We found that the impact of QI projects in healthcare settings should be initiated following the Plan–Do–Study–Act cycle and evaluated long-term effects while widening the scope of QI evaluation with sustainability. This study can serve as a guide for healthcare professionals to use a number of statistical methodologies in their QI evaluations.
Internet Gaming Disorder in Early Adolescents: Gender and Depression Differences in a Latent Growth Model
Authors: Wang Rong , Yang Shuqi , Yan Yun , Tian Yu , Wang Peng
Published: September 2021

Background: Studies have shown that many Internet game players may have experienced Internet gaming disorder (IGD), which is thought to coexist with a variety of cognitive and psychological disorders, such as depression. A three-year, four-point longitudinal tracking study was conducted to examine the trajectory of IGD of Chinese early adolescents, as well as the predictive level of gender and depression for IGD. Participants (N = 316) completed questionnaires assessing IGD and depression at the time of the T1, T2, T3, and T4. This study adopted the widely used latent growth model for data analysis. The results showed that, in the early stage of adolescence, (1) the development trajectory of individual IGD was shown as a nonlinear latent variable growth model; the IGD was significantly higher than zero when teenagers were first measured (sixth grade); and, while on the rise, its growth rate is gradually slowing. (2) Gender can significantly predict the development trajectory of individual IGD. (3) Individuals with a high initial level of depression usually have a high initial level of IGD, individuals with a large range of depression display a large range of IGD, and those with a rapid rate of depression change show similar change in their IGD. In sum, this study provided an empirical basis for the prevention and intervention of IGD in early adolescents.
An Improved Protocol for Asymbiotic Seed Germination and Seedling Development of Paphiopedilum tigrinum
Authors: Yao Linling , Huang Jialin , Zhang Shibao
Published: September 2021

Paphiopedilum tigrinum is an endangered orchid with high ornamental value. However, seed germination and seedling regeneration in P. tigrinum is very difficult in vitro. Little is known about why P. tigrinum seedlings are difficult to propagate or how to improve the seed germination and seedling rates of this species. In this study, we investigated the developmental process of P. tigrinum from asymbiotic seed germination to seedling rooting by comparing it with P. appletoniantum, a much easier species for germination and seedling formation. We found that asymbiotic seed germination in P. tigrinum is limited by severe browning of the protocorm at the seed germination stage, and protocorm rooting at the differentiation stage was also proved to be difficult. The optimal medium for seed germination of P. tigrinum was a modified Harvais (mHa) medium supplemented with 0.5 mg·L−1 kinetin (Kin), 0.1 g·L−1 activated charcoal (AC) and 100 mL·L−1 coconut water (CW). At the protocorm differentiation stage, seedlings with 1–2 leaves were obtained on a 1/4 MS medium supplemented with 1.0 mg·L−1 6-benzylaminopurin (BA), 0.3 g·L−1 AC and 50–100 mL·L−1 CW after culturing for 120 day. At the seedling subculture stage, a 1/2 MS medium supplemented with 0.5–1.5 g·L−1 AC and 100 mL·L−1 CW was better for leaf and root growth of P. tigrinum. At the rooting stage, a 1/2 MS medium supplemented with 1.0 g·L−1 AC, 0.5 g·L−1 dolomite flour, 15 g·L−1 potato homogenate and 30 g·L−1 banana homogenate was most suitable for the growth and rooting of seedlings. This study has established an effective protocol for seed germination and seedling regeneration of P. tigrinum.
New Insight into the Phylogeny and Taxonomy of Cultivated and Related Species of Crataegus in China, Based on Complete Chloroplast Genome Sequencing
Authors: Hu Guanglong , Wang Yiheng , Wang Yan , Zheng Shuqi , Dong Wenxuan , Dong Ningguang
Published: September 2021

Hawthorns (Crataegus L.) are one of the most important processing and table fruits in China, due to their medicinal properties and health benefits. However, the interspecific relationships and evolution history of cultivated Crataegus in China remain unclear. Our previously published data showed C. bretschneideri may be derived from the hybridization of C. pinnatifida with C. maximowiczii, and that introgression occurs between C. hupehensis, C. pinnatifida, and C. pinnatifida var. major. In the present study, chloroplast sequences were used to further elucidate the phylogenetic relationships of cultivated Crataegus native to China. The chloroplast genomes of three cultivated species and one related species of Crataegus were sequenced for comparative and phylogenetic analyses. The four chloroplast genomes of Crataegus exhibited typical quadripartite structures and ranged from 159,607 bp (C. bretschneideri) to 159,875 bp (C. maximowiczii) in length. The plastomes of the four species contained 113 genes consisting of 79 protein-coding genes, 30 tRNA genes, and 4 rRNA genes. Six hypervariable regions (ndhC-trnV(UAC)-trnM(CAU), ndhA, atpH-atpI, ndhF, trnR(UCU)-atpA, and ndhF-rpl32), 196 repeats, and a total of 386 simple sequence repeats were detected as potential variability makers for species identification and population genetic studies. In the phylogenomic analyses, we also compared the entire chloroplast genomes of three published Crataegus species: C. hupehensis (MW201730.1), C. pinnatifida (MN102356.1), and C. marshallii (MK920293.1). Our phylogenetic analyses grouped the seven Crataegus taxa into two main clusters. One cluster included C. bretschneideri, C. maximowiczii, and C. marshallii, whereas the other included C. hupehensis, C. pinnatifida, and C. pinnatifida var. major. Taken together, our findings indicate that C. maximowiczii is the maternal origin of C. bretschneideri. This work provides further evidence of introgression between C. hupehensis, C. pinnatifida, and C. pinnatifida var. major, and suggests that C. pinnatifida var. major might have been artificially selected and domesticated from hybrid populations, rather than evolved from C. pinnatifida.
Post-COVID-19 Necrotizing Pneumonia in Patients on Invasive Mechanical Ventilation
Authors: Hidron Alicia , Quiceno William , Cardeño John J. , Roncancio Gustavo , García Cristian
Published: September 2021

(1) Background: Few reports of necrotizing pneumonia in patients with COVID-19 have been published. We have observed an elevated incidence at two hospitals in our city, suggesting this complication is not uncommon, and may have been overlooked. (2) Methods: This article presents a retrospective, descriptive cohort study that was undertaken from 22 March 2020 to 15 June 2021 in two tertiary care hospitals in Medellín, Colombia. All adult patients admitted to the intensive care unit (ICU) for respiratory failure related to confirmed COVID-19, on invasive mechanical ventilation (IMV), with imaging or surgical findings documenting necrotizing pneumonia (NP) were included. (3) Results: Of 936 patients with COVID-19 that required IMV, 42 (4.5%) developed NP. Overall mortality was 57% and in-hospital mortality was 71%, occurring 15–79 days after COVID-19 diagnosis. NP was diagnosed at a median of 27 days after COVID-19 symptom onset and 15.5 days after initiation of IMV. Infections were polymicrobial in 52.4% of patients. Klebsiella pneumoniae (57%) and Pseudomonas aeruginosa (33%) were the most common etiologic agents. Pulmonary embolism (PE) was documented in 13 patients overall (31%), and in 50% of patients who underwent an angioCT. Drainage and/or surgical procedures were performed on 19 patients (45.2%) with a 75% mortality rate. (4) Conclusions: In our experience, NP is a relatively common, albeit neglected, complication in mechanically ventilated COVID-19 patients, possibly originating in poorly vascularized areas of lung parenchyma. Associated mortality is high. Although drainage procedures did not seem to favorably impact patient outcomes, diagnosis and treatment were late events in the overall disease course, suggesting that early recognition and timely treatment could have a positive impact on prognosis.
Engaging with Transformative Paradigms in Mental Health
Authors: Whitaker Louise , Smith Fiona L. , Brasier Catherine , Petrakis Melissa , Brophy Lisa
Published: September 2021

When graduates of Australian social work courses embark on a career in mental health, the systems they enter are complex, fragmented and evolving. Emerging practitioners will commonly be confronted by the loneliness, social exclusion, poverty and prejudice experienced by people living with mental distress; however, social work practice may not be focused on these factors. Instead, in accordance with the dominant biomedical perspective, symptom and risk management may predominate. Frustration with the limitations evident in this approach has seen the United Nations call for the transformation of mental health service delivery. Recognising paradigmatic influences on mental health social work may lead to a more considered enactment of person centred, recovery and rights-based approaches. This paper compares and contrasts influences of neo-liberalism, critical theory, human rights and post-structuralism on mental health social work practice. In preparing social work practitioners to recognise the influence of, and work more creatively with, intersecting paradigms, social work educators strive to foster a transformative approach to mental health practice that straddles discourses.
Nursing-Sensitive Outcomes among Patients Cared for in Paediatric Intensive Care Units: A Scoping Review
Authors: Danielis Matteo , Castellano Adele , Mattiussi Elisa , Palese Alvisa
Published: September 2021

Measuring the effectiveness of nursing interventions in intensive care units has been established as a priority. However, little is reported about the paediatric population. The aims of this study were (a) to map the state of the art of the science in the field of nursing-sensitive outcomes (NSOs) in paediatric intensive care units (PICUs) and (b) to identify all reported NSOs documented to date in PICUs by also describing their metrics. A scoping review was conducted by following the framework proposed by Arksey and O’Malley. Fifty-eight articles were included. Publications were mainly authored in the United States and Canada (n = 28, 48.3%), and the majority (n = 30, 51.7%) had an observational design. A total of 46 NSOs were documented. The most reported were related to the clinical (n = 83), followed by safety (n = 41) and functional (n = 18) domains. Regarding their metrics, the majority of NSOs were measured in their occurrence using quantitative single measures, and a few validated tools were used to a lesser extent. No NSOs were reported in the perceptual domain. Nursing care of critically ill children encompasses three levels: improvement in clinical performance, as measured by clinical outcomes; assurance of patient care safety, as measured by safety outcomes; and promotion of fundamental care needs, as measured by functional outcomes. Perceptual outcomes deserve to be explored.
Effects of Physical Activity and Psychological Modification-Based Intervention on Physical Fitness, Physical Activity and Its Related Psychological Variables in Female Adolescents
Authors: Kim YoungHo , Park InKyoung
Published: September 2021

Background: The current study investigated the effects of an intervention incorporating physical activity and psychological modification strategy on physical fitness, physical activity levels, and psychological variables related to physical activity in female adolescents. Methods: Sixty female adolescents were recruited from H Middle School. Among them, 30 females (Mage = 14.35 years) were randomly assigned to the experimental group and the rest of 30 to the control group (Mage = 14.47 years) and voluntarily participated in the 12-week intervention. Results: The results indicated that the physical activity stage of female adolescents in the experimental group significantly increased over the 12-week intervention. The results revealed that all of psychological variables in the experimental group significantly improved over the intervention, while participants in the experimental group showed significantly higher scores on most of psychological variables, except cons, than those in the control group after the intervention. Moreover, most of physical fitness components in the experimental group significantly increased over the intervention. Conclusions: The current study confirmed that the physical activity-related psychological intervention was feasible for improving physical and psychological health among female adolescents.
Personal and Emotional Factors of Nursing Professionals Related to Coping with End-of-Life Care: A Cross-Sectional Study
Authors: Povedano-Jiménez María , Ropero-Padilla Carmen , Rodriguez-Arrastia Miguel , García-Caro María Paz
Published: September 2021

The death of a patient can be a traumatic event, causing emotional and psychological distress in professional nurses and potentially hampering the quality of their care. Optimal self-perceived coping with death involves valuing these difficult situations as challenges and actively coping with work-related stress during the care of the dying patient. Thus, the aim of this study was to assess Spanish nurses’ self-perceived competence with patient death and investigate its relationship with their personality traits, anxiety and fear of death. A cross-sectional study based on a web-based survey was conducted. A sample of 534 Spanish nurses provided socio-demographic information and answered validated questionnaires. Most participants perceived their coping with death as optimal. Men and nurses older than 31 years coped better with death. Professionals with an optimal self-perception showed significantly lower scores on all personality dimensions evaluated, while a higher level of the anxiety trait predicted worse coping. Although with medium explanatory power, psychoticism, anxiety, and fear of death were the main predictors of the development of optimal coping with death among Spanish nurses. These characteristics together with information from the work environment and evidence-based practice could help to develop better routines and contexts of care for nurses working in end-of-life care.
Anti-Oxidative and Immune Regulatory Responses of THP-1 and PBMC to Pulsed EMF Are Field-Strength Dependent
Authors: Groiss Silvia , Lammegger Roland , Brislinger Dagmar
Published: September 2021

Innate immune cells react to electromagnetic fields (EMF) by generating reactive oxygen species (ROS), crucial intracellular messengers. Discrepancies in applied parameters of EMF studies, e.g., flux densities, complicate direct comparison of downstream anti-oxidative responses and immune regulatory signaling. We therefore compared the impact of different EMF flux densities in human leukemic THP1 cells and peripheral blood mononuclear cells (PBMC) of healthy donors to additionally consider a potential disparate receptivity based on medical origin. ROS levels increased in THP1 cells stimulated with lipopolysaccharide (LPS) after one hour of EMF exposure. Moreover, weak EMF mitigated the depletion of the reducing agent NAD(P)H in THP1. Neither of these effects occurred in PBMC. Landscaping transcriptional responses to varied EMF revealed elevation of the anti-oxidative enzymes PRDX6 (2-fold) and DHCR24 (6-fold) in THP1, implying involvement in lipid metabolism. Furthermore, our study confirmed anti-inflammatory effects of EMF by 6-fold increased expression of IL10. Strikingly, THP1 responded to weak EMF, while PBMC were primarily affected by strong EMF, yet with severe cellular stress and enhanced rates of apoptosis, indicated by HSP70 and caspase 3 (CASP3). Taken together, our results emphasize an altered susceptibility of immune cells of different origin and associate EMF-related effects with anti-inflammatory signaling and lipid metabolism.
Evidence of Violations of the International Code of Marketing of Breast-Milk Substitutes since the Adoption by the World Health Assembly in 1981: A Systematic Scoping Review Protocol
Authors: Becker Genevieve E. , Ching Constance , Zambrano Paul , Burns Allison , Cashin Jennifer , Mathisen Roger
Published: September 2021

This is the protocol for a scoping review that aims to systematically explore and summarise the published evidence of violations of the International Code of Marketing of Breast-milk Substitutes (the Code) and subsequent World Health Assembly Resolutions globally. The planned scoping review will seek to identify what research has been conducted on the topic, examine the geographic spread and nature of violations, and summarise knowledge gaps. The Code was adopted in 1981 by the World Health Assembly to protect infant health, in particular from aggressive and inappropriate marketing of breastmilk substitutes including formula and related products. Non-compliance with the Code or violations are described in reports, however, no existing systematic review of the global research appears to have been conducted that encompasses the varied disciplines including health, economics, and gender. The review will inform international and national decision-makers on the nature of violations and potentially highlight the need for new modalities to regulate this marketing. The proposed scoping review will use the six-step process of Arksey and O’Malley which includes defining the research question; identifying the relevant literature; selecting studies; charting the data; collating, summarising and reporting the findings; and will include a consultative group.
Label-Free Investigations on the G Protein Dependent Signaling Pathways of Histamine Receptors
Authors: Seibel-Ehlert Ulla , Plank Nicole , Inoue Asuka , Bernhardt Guenther , Strasser Andrea
Published: September 2021

G protein activation represents an early key event in the complex GPCR signal transduction process and is usually studied by label-dependent methods targeting specific molecular events. However, the constrained environment of such “invasive” techniques could interfere with biological processes. Although histamine receptors (HRs) represent (evolving) drug targets, their signal transduction is not fully understood. To address this issue, we established a non-invasive dynamic mass redistribution (DMR) assay for the human H1–4Rs expressed in HEK cells, showing excellent signal-to-background ratios above 100 for histamine (HIS) and higher than 24 for inverse agonists with pEC50 values consistent with literature. Taking advantage of the integrative nature of the DMR assay, the involvement of endogenous Gαq/11, Gαs, Gα12/13 and Gβγ proteins was explored, pursuing a two-pronged approach, namely that of classical pharmacology (G protein modulators) and that of molecular biology (Gα knock-out HEK cells). We showed that signal transduction of hH1–4Rs occurred mainly, but not exclusively, via their canonical Gα proteins. For example, in addition to Gαi/o, the Gαq/11 protein was proven to contribute to the DMR response of hH3,4Rs. Moreover, the Gα12/13 was identified to be involved in the hH2R mediated signaling pathway. These results are considered as a basis for future investigations on the (patho)physiological role and the pharmacological potential of H1–4Rs.
Cardiac and Renal SARS-CoV-2 Viral Entry Protein Regulation by Androgens and Diet: Implications for Polycystic Ovary Syndrome and COVID-19
Authors: Rezq Samar , Huffman Alexandra M. , Basnet Jelina , Yanes Cardozo Licy L. , Romero Damian G.
Published: September 2021

The susceptibility and the severity of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are associated with hyperandrogenism, obesity, and preexisting pulmonary, metabolic, renal, and cardiac conditions. Polycystic ovary syndrome (PCOS), the most common endocrine disorder in premenopausal women, is associated with obesity, hyperandrogenism, and cardiometabolic dysregulations. We analyzed cardiac, renal, circulatory, and urinary SARS-CoV-2 viral entry proteins (ACE2, TMPRSS2, TMPRSS4, furin, cathepsin L, and ADAM17) and androgen receptor (AR) expression, in a peripubertal androgen exposure model of PCOS. Peripubertal female mice were treated with dihydrotestosterone (DHT) and low (LFD) or high (HFD) fat diet for 90 days. HFD exacerbated DHT-induced increase in body weight, fat mass, and cardiac and renal hypertrophy. In the heart, DHT upregulated AR protein in both LFD and HFD, ACE2 in HFD, and ADAM17 in LFD. In the kidney, AR protein expression was upregulated by both DHT and HFD. Moreover, ACE2 and ADAM17 were upregulated by DHT in both diets. Renal TMPRSS2, furin, and cathepsin L were upregulated by DHT and differentially modulated by the diet. DHT upregulated urinary ACE2 in both diets, while neither treatment modified serum ACE2. Renal AR mRNA expression positively correlated with Ace2, Tmprss2, furin, cathepsin L, and ADAM17. Our findings suggest that women with PCOS could be a population with a high risk of COVID-19-associated cardiac and renal complications. Furthermore, our study suggests that weight loss by lifestyle modifications (i.e., diet) could potentially mitigate COVID-19-associated deleterious cardiorenal outcomes in women with PCOS.
Stress and the Role of the Gut–Brain Axis in the Pathogenesis of Schizophrenia: A Literature Review
Authors: Vafadari Behnam
Published: September 2021

Schizophrenia is a severe neuropsychiatric disorder, and its etiology remains largely unknown. Environmental factors have been reported to play roles in the pathogenesis of schizophrenia, and one of the major environmental factors identified for this disorder is psychosocial stress. Several studies have suggested that stressful life events, as well as the chronic social stress associated with city life, may lead to the development of schizophrenia. The other factor is the gut–brain axis. The composition of the gut microbiome and alterations thereof may affect the brain and may lead to schizophrenia. The main interest of this review article is in overviewing the major recent findings on the effects of stress and the gut–brain axis, as well as their possible bidirectional effects, in the pathogenesis of schizophrenia.
CRISPR-Knockout of CSE Gene Improves Saccharification Efficiency by Reducing Lignin Content in Hybrid Poplar
Authors: Jang Hyun-A , Bae Eun-Kyung , Kim Min-Ha , Park Su-Jin , Choi Na-Young , Pyo Seung-Won , Lee Chanhui , Jeong Ho-Young , Lee Hyoshin , Choi Young-Im , Ko Jae-Heung
Published: September 2021

Caffeoyl shikimate esterase (CSE) has been shown to play an important role in lignin biosynthesis in plants and is, therefore, a promising target for generating improved lignocellulosic biomass crops for sustainable biofuel production. Populus spp. has two CSE genes (CSE1 and CSE2) and, thus, the hybrid poplar (Populus alba × P. glandulosa) investigated in this study has four CSE genes. Here, we present transgenic hybrid poplars with knockouts of each CSE gene achieved by CRISPR/Cas9. To knockout the CSE genes of the hybrid poplar, we designed three single guide RNAs (sg1–sg3), and produced three different transgenic poplars with either CSE1 (CSE1-sg2), CSE2 (CSE2-sg3), or both genes (CSE1/2-sg1) mutated. CSE1-sg2 and CSE2-sg3 poplars showed up to 29.1% reduction in lignin deposition with irregularly shaped xylem vessels. However, CSE1-sg2 and CSE2-sg3 poplars were morphologically indistinguishable from WT and showed no significant differences in growth in a long-term living modified organism (LMO) field-test covering four seasons. Gene expression analysis revealed that many lignin biosynthetic genes were downregulated in CSE1-sg2 and CSE2-sg3 poplars. Indeed, the CSE1-sg2 and CSE2-sg3 poplars had up to 25% higher saccharification efficiency than the WT control. Our results demonstrate that precise editing of CSE by CRISPR/Cas9 technology can improve lignocellulosic biomass without a growth penalty.
Perturbation of TM6SF2 Expression Alters Lipid Metabolism in a Human Liver Cell Line
Authors: Pant Asmita , Chen Yue , Kuppa Annapurna , Du Xiaomeng , Halligan Brian D. , Speliotes Elizabeth K.
Published: September 2021

Non-alcoholic fatty liver disease (NAFLD) is caused by excess lipid accumulation in hepatocytes. Genome-wide association studies have identified a strong association of NAFLD with non-synonymous E167K amino acid mutation in the transmembrane 6 superfamily member 2 (TM6SF2) protein. The E167K mutation reduces TM6SF2 stability, and its carriers display increased hepatic lipids and lower serum triglycerides. However, the effects of TM6SF2 on hepatic lipid metabolism are not completely understood. We overexpressed wild-type or E167K variant of TM6SF2 or knocked down TM6SF2 expression in lipid-treated Huh-7 cells and used untargeted lipidomic analysis, RNAseq transcriptome analysis, and fluorescent imaging to determine changes in hepatic lipid metabolism. Both TM6SF2 knockdown and E167K overexpression increased hepatic lipid accumulation, while wild-type overexpression decreased acylglyceride levels. We also observed lipid chain remodeling for acylglycerides by TM6SF2 knockdown, leading to a relative increase in species with shorter, more saturated side chains. RNA-sequencing revealed differential expression of several lipid metabolizing genes, including genes belonging to AKR1 family and lipases, primarily in cells with TM6SF2 knockdown. Taken together, our data show that overexpression of TM6SF2 gene or its loss-of-function changes hepatic lipid species composition and expression of lipid metabolizing genes. Additionally, our data further confirms a loss-of-function effect for the E167K variant.
Prenatal and Postnatal Methyl-Modulator Intervention Corrects the Stress-Induced Glucocorticoid Response in Low-Birthweight Rats
Authors: Nemoto Takahiro , Kakinuma Yoshihiko
Published: September 2021

Low body weight at birth has been shown to be a risk factor for future metabolic disorders, as well as stress response abnormalities and depression. We showed that low-birthweight rats had prolonged high blood corticosterone levels after stress exposure, and that an increase in Gas5 lncRNA, a decoy receptor for glucocorticoid receptors (GRs), reduces glucocorticoid responsiveness. Thus, we concluded that dampened pituitary glucocorticoid responsiveness disturbed the glucocorticoid feedback loop in low-birthweight rats. However, it remains unclear whether such glucocorticoid responsiveness is suppressed solely in the pituitary or systemically. The expression of Gas5 lncRNA increased only in the pituitary, and the intact induction of expression of the GR co-chaperone factor Fkbp5 against dexamethasone was seen in the liver, muscle, and adipose tissue. Intervention with a methyl-modulator diet (folate, VB12, choline, betaine, and zinc) immediately before or one week after delivery reversed the expression level of Gas5 lncRNA in the pituitary of the offspring. Consequently, it partially normalized the blood corticosterone levels after restraint stress exposure. In conclusion, the mode of glucocorticoid response in low-birthweight rats is impaired solely in the pituitary, and intervention with methyl-modulators ameliorates the impairment, but with a narrow therapeutic time window.
The Anti-Atherosclerotic Action of FFAR4 Agonist TUG-891 in ApoE–Knockout Mice Is Associated with Increased Macrophage Polarization towards M2 Phenotype
Authors: Kiepura Anna , Stachyra Kamila , Wiśniewska Anna , Kuś Katarzyna , Czepiel Klaudia , Suski Maciej , Ulatowska-Białas Magdalena , Surmiak Marcin , Olszanecki Rafał
Published: September 2021

Background: Over the past few years, a better understanding of the biology of G-protein coupled receptors (GPRs) has led to the identification of several receptors as novel targets for free fatty acids (FFAs). FFAR4 has received special attention in the context of chronic inflammatory diseases, including atherosclerosis, obesity and NAFLD, through to its anti-inflammatory effect. Methods: The present study investigates the influence of prolonged treatment with TUG-891-FFAR4 agonist on the development of atherosclerosis plaque in apoE-knockout mice, using morphometric and molecular methods. Results: TUG-891 administration has led to the reduction of atherosclerotic plaque size and necrotic cores in an apoE-knockout mice model. TUG-891-treated mice were administered subcutaneously at a dose of 20 mg/kg three times a week for 4 months. The FFAR4 agonist reduced the content of pro-inflammatory M1-like macrophages content in atherosclerotic plaques, as evidenced by immunohistochemical phenotyping and molecular methods. In atherosclerotic plaque, the population of smooth muscle cells increased as evidenced by α-SMA staining. We observed changes in G-CSF and eotaxin markers in the plasma of mice; changes in the levels of these markers in the blood may be related to macrophage differentiation. Importantly, we observed a significant increase in M2-like macrophage cells in atherosclerotic plaque and peritoneum. Conclusions: Prolonged administration of TUG-891 resulted in significant amelioration of atherogenesis, providing evidence that the strategy based on macrophage phenotype switching toward an M2-like activation state via stimulation of FFAR4 receptor holds promise for a new approach in the prevention or treatment of atherosclerosis.
Neuroprotective Effects of Cannabidiol but Not Δ9-Tetrahydrocannabinol in Rat Hippocampal Slices Exposed to Oxygen-Glucose Deprivation: Studies with Cannabis Extracts and Selected Cannabinoids
Authors: Landucci Elisa , Mazzantini Costanza , Lana Daniele , Davolio Pier Luigi , Giovannini Maria Grazia , Pellegrini-Giampietro Domenico E.
Published: September 2021

(1) Background: Over the past 10 years, a number of scientific studies have demonstrated the therapeutic potential of cannabinoid compounds present in the Cannabis Sativa and Indica plants. However, their role in mechanisms leading to neurodegeneration following cerebral ischemia is yet unclear. (2) Methods: We investigated the effects of Cannabis extracts (Bedrocan, FM2) or selected cannabinoids (Δ9-tetrahydrocannabinol (THC), cannabidiol (CBD), and cannabigerol) in rat organotypic hippocampal slices exposed to oxygen-glucose deprivation (OGD), an in vitro model of forebrain global ischemia. Cell death in the CA1 subregion of slices was quantified by propidium iodide fluorescence, and morphological analysis and tissue organization were examined by immunohistochemistry and confocal microscopy. (3) Results: Incubation with the Bedrocan extract or THC exacerbated, whereas incubation with the FM2 extract or cannabidiol attenuated CA1 injury induced by OGD. Δ9-THC toxicity was prevented by CB1 receptor antagonists, the neuroprotective effect of cannabidiol was blocked by TRPV2, 5-HT1A, and PPARγ antagonists. Confocal microscopy confirmed that CBD, but not THC, had a significant protective effect toward neuronal damage and tissue disorganization caused by OGD in organotypic hippocampal slices. (4) Conclusions: Our results suggest that cannabinoids play different roles in the mechanisms of post-ischemic neuronal death. In particular, appropriate concentrations of CBD or CBD/THC ratios may represent a valid therapeutic intervention in the treatment of post-ischemic neuronal death.
Biology, Ecology, and Pest Management of the Tarnished Plant Bug, Lygus lineolaris (Palisot de Beauvois) in Southern Row Crops
Authors: George Justin , Glover James P. , Gore Jeffrey , Crow Whitney D. , Reddy Gadi V. P.
Published: September 2021

The tarnished plant bug, Lygus lineolaris (Palisot de Beauvois), (Hemiptera: Miridae) is considered the most damaging pest of cotton (Gossypium hirsutum L.) in the mid-southern United States, although it is established throughout the United States, southern Canada, and northern Mexico. The introduction of transgenic crops for the control of moths in the Heliothine complex and eradication of the boll weevil, Anthonomus grandis, from much of the United States led to greatly reduced pesticide use in cotton fields, which allowed L. lineolaris to emerge as a new primary pest of cotton in the mid-southern United States. Since the publication of a review by Layton (2000) on damage caused by Lygus lineolaris, many new studies have been published on the changes in host range, population dynamics, sampling methods and thresholds, cultural practices, sex pheromones and attractant blends, novel pesticides and insecticide resistance mechanisms, olfactory and feeding behaviors, introduction of biological control agents, host-plant resistance mechanisms, and new molecular and genetic tools for integrated pest management of Lygus species in cotton and other important crops. Here, we review and discuss the latest developments in L. lineolaris research in the last two decades.
Estimation of Ixodes ricinus (Acari: Ixodidae) Populations of Kaylaka Park in the Town of Pleven, Bulgaria
Authors: Blazhev Alexander , Atanasova Milena , Kostov Krasimir , Doychinova Tsetsa , Blazheva Svetla , Karcheva Milena
Published: September 2021

(1) Background: Ticks are vectors of a large number of pathogenic microorganisms, which cause serious diseases in both humans and animals. Kaylaka Park is located in northern Bulgaria close to the city of Pleven. Part of the park is urbanized and visited daily by many citizens. The aim of our study was to determine the presence and distribution of hard ticks in the park area by surveying and comparing four urbanized with four wild areas. (2) Methods: Ticks were collected by flagging from 2016 to 2020 during the spring–summer season (March–July). Air temperature, relative humidity, collection time and flagging area were measured during the campaign. (3) Results: A total of 622 ticks were collected: 285 females (46%), 272 (44%) males and 64 (10%) nymphs. All were identified as Ixodes ricinus. Wild areas showed statistically significant higher values of ticks collected per minute (p = 0.009) and nymph densities (p = 0.003) compared to urbanized sampling sites. Other densities indices did not have a significant difference between urban and wild areas. Highest numbers of Ixodes ticks were collected at a temperature of 20 °C and at 60% relative humidity. The active questing began in March, peaked in end of April and declined in June. (4) Conclusions: In the present study, we found that ecological factors in the Kaylaka Park area are favourable for the development and distribution of tick populations. The results give us reason to consider that there is a high risk to visitors from tick bites in the Kaylaka Park area.
Elevated Epidermal Growth Factor (EGF) as Candidate Biomarker of Mood Disorders—Longitudinal Study in Adolescent and Young Adult Patients
Authors: Skibinska Maria , Kapelski Pawel , Dmitrzak-Weglarz Monika , Lepczynska Natalia , Pawlak Joanna , Twarowska-Hauser Joanna , Szczepankiewicz Aleksandra , Rajewska-Rager Aleksandra
Published: September 2021

Bipolar disorder (BD) is a chronic mental disorder that affects more than 1% of the population worldwide. Over 65% of patients experience early onset of the disease. Most cases of juvenile bipolar disorder begin with a depressed mood episode, and up to 50% of youth initially diagnosed with major depression go onto developing a BD. Our study aimed to find biomarkers of diagnosis conversion in young patients with mood disorders. We performed a two-year follow-up study on 79 adolescent patients diagnosed with MDD or BD, with a detailed clinical assessment at five visits. We monitored diagnosis change from MDD to BD. The control group consisted of 31 healthy youths. According to the neurodevelopmental and neuroimmunological hypotheses of mood disorders, we analyzed serum levels of brain-derived neurotrophic factor (BDNF), proBDNF, epidermal growth factor (EGF), migration inhibitory factor (MIF), stem cell factor (SCF), and correlations with clinical factors. We detected a significant disease-dependent increase in EGF level in MDD and BP patients at baseline exacerbation of depressive or hypomanic/manic episodes as well as in euthymic state compared to healthy controls. No potential biological predictors of disease conversion were found. Replication studies on a larger cohort of patients are needed.
Clinical Usefulness of FRAX Score for Predicting Sarcopenia in Patients with Chronic Liver Disease
Authors: Saeki Chisato , Saito Mitsuru , Kanai Tomoya , Nakano Masanori , Oikawa Tsunekazu , Torisu Yuichi , Saruta Masayuki , Tsubota Akihito
Published: September 2021

We investigated the usefulness of the Fracture Risk Assessment tool (FRAX) for predicting sarcopenia in chronic liver disease (CLD). In this cross-sectional study, we evaluated 321 patients with CLD. The FRAX with and without bone mineral density (BMD) was employed to calculate the 10-year risks of major osteoporotic and hip fractures. The FRAX score for high fracture risk was defined as a 10-year major osteoporotic fracture probability of ≥20% or a 10-year hip fracture probability of ≥3%. The diagnosis of sarcopenia was based on the Japan Society of Hepatology criteria. According to the FRAX, with and without BMD, 134 (41.7%) and 193 (60.1%) patients had a high fracture risk, respectively. The high fracture risk group had a significantly higher frequency of sarcopenia than the non-high fracture risk group. FRAX scores of major osteoporotic and hip fractures were negatively correlated with handgrip strength and muscle mass. Using the FRAX with BMD, the cutoff scores of major osteoporotic and hip fractures for predicting sarcopenia were 8.55% (sensitivity/specificity, 0.847/0.568) and 3.35% (0.729/0.746), respectively. Using the FRAX without BMD, they were 18.5% (0.635/0.725) and 7.65% (0.729/0.758), respectively. The FRAX is a simple and convenient screening tool for predicting sarcopenia in patients with CLD.
Diversity of Colletotrichum Species Associated with Olive Anthracnose Worldwide
Authors: Moral Juan , Agustí-Brisach Carlos , Raya Maria Carmen , Jurado-Bello José , López-Moral Ana , Roca Luis F. , Chattaoui Mayssa , Rhouma Ali , Nigro Franco , Sergeeva Vera , Trapero Antonio
Published: September 2021

Olive anthracnose caused by Colletotrichum species causes dramatic losses of fruit yield and oil quality worldwide. A total of 185 Colletotrichum isolates obtained from olives and other hosts showing anthracnose symptoms in Spain and other olive-growing countries over the world were characterized. Colony and conidial morphology, benomyl-sensitive, and casein-hydrolysis activity were recorded. Multilocus alignments of ITS, TUB2, ACT, CHS-1, HIS3, and/or GAPDH were conducted for their molecular identification. The pathogenicity of the most representative Colletotrichum species was tested to olive fruits and to other hosts, such as almonds, apples, oleander, sweet oranges, and strawberries. In general, the phenotypic characters recorded were not useful to identify all species, although they allowed the separation of some species or species complexes. ITS and TUB2 were enough to infer Colletotrichum species within C. acutatum and C. boninense complexes, whereas ITS, TUB2, ACT, CHS-1, HIS-3, and GADPH regions were necessary to discriminate within the C. gloesporioides complex. Twelve Colletotrichum species belonging to C. acutatum, C. boninense, and C. gloeosporioides complexes were identified, with C. godetiae being dominant in Spain, Italy, Greece, and Tunisia, C. nymphaeae in Portugal, and C. fioriniae in California. The highest diversity with eight Colletotrichum spp. was found in Australia. Significant differences in virulence to olives were observed between isolates depending on the Colletotrichum species and host origin. When other hosts were inoculated, most of the Colletotrichum isolates tested were pathogenic in all the hosts evaluated, except for C. siamense to apple and sweet orange fruits, and C. godetiae to oleander leaves.
MRI Deep Learning-Based Solution for Alzheimer’s Disease Prediction
Authors: Saratxaga Cristina L. , Moya Iratxe , Picón Artzai , Acosta Marina , Moreno-Fernandez-de-Leceta Aitor , Garrote Estibaliz , Bereciartua-Perez Arantza
Published: September 2021

Background: Alzheimer’s is a degenerative dementing disorder that starts with a mild memory impairment and progresses to a total loss of mental and physical faculties. The sooner the diagnosis is made, the better for the patient, as preventive actions and treatment can be started. Although tests such as the Mini-Mental State Tests Examination are usually used for early identification, diagnosis relies on magnetic resonance imaging (MRI) brain analysis. Methods: Public initiatives such as the OASIS (Open Access Series of Imaging Studies) collection provide neuroimaging datasets openly available for research purposes. In this work, a new method based on deep learning and image processing techniques for MRI-based Alzheimer’s diagnosis is proposed and compared with previous literature works. Results: Our method achieves a balance accuracy (BAC) up to 0.93 for image-based automated diagnosis of the disease, and a BAC of 0.88 for the establishment of the disease stage (healthy tissue, very mild and severe stage). Conclusions: Results obtained surpassed the state-of-the-art proposals using the OASIS collection. This demonstrates that deep learning-based strategies are an effective tool for building a robust solution for Alzheimer’s-assisted diagnosis based on MRI data.
Is Industry Size a Carrier for Wage Inequality? A Panel Study Addressing Independent Variables of Inherently Different Sizes across Units
Authors: Aarstad Jarle , Kvitastein Olav Andreas
Published: September 2021

We address how independent variables of inherently different sizes across units, e.g., small vs. large industries, in panel regression is an advantage interpretively. Analyzing a Norwegian industry panel, we find that wage inequality is a function of industry size, particularly size increase, in an absolute number of firms. A possible reason is that specialized skilled employees negotiate higher wages when there are many legal entities. The findings can also imply that wage inequality is more sensitive to random change, particularly an increase, in large rather than small industries. We conclude that particularly large industries are positive carriers of wage inequality and discuss potential underlying causal mechanisms such as monopolistic competition.
Modes and Forms of Knowledge of Farming Entrepreneurship: An Ethnographic Analysis among Small Farmers in NW Italy
Authors: Fontefrancesco Michele Filippo
Published: September 2021

This article investigates the modes and forms of knowledge underpinning farming entrepreneurship through an ethnographic case study of Alessandria province in NW Italy. It shows that farming entrepreneurs base their decisions on explicit and implicit knowledge encompassing forms of knowledge linked to the environment where they live, their trade, the characteristics of their firms, issues concerning their family and private life, and even the emotions linked with their surroundings. All these forms of knowledge inform their vision of their future and guide them in their choices in terms of investments and crop selection. Accordingly, the article argues that farming entrepreneurship is embedded in the locale.
Primary Extracranial Meningiomas of the Head and Neck
Authors: Umana Giuseppe Emmanuele , Scalia Gianluca , Vats Atul , Pompili Gianluca , Barone Fabio , Passanisi Maurizio , Graziano Francesca , Maugeri Rosario , Tranchina Maria Grazia , Cosentino Sebastiano , Ippolito Massimo , Tomasi Santino Ottavio , Raudino Giuseppe , Chaurasia Bipin , Iacopino Domenico Gerardo , Nicoletti Giovanni Federico , Cicero Salvatore , Strigari Lidia , Perrotta Rosario Emanuele
Published: September 2021

Meningiomas represent the most common benign histological tumor of the central nervous system. Usually, meningiomas are intracranial, showing a typical dural tail sign on brain MRI with Gadolinium, but occasionally they can infiltrate the skull or be sited extracranially. We present a systematic review of the literature on extracranial meningiomas of the head and neck, along with an emblematic case of primary extracranial meningioma (PEM), which provides further insights into PEM management. A literature search according to the PRISMA statement was conducted from 1979 to June 2021 using PubMed, Web of Science, Google Scholar, and Scopus databases, searching for relevant Mesh terms (primary extracranial meningioma) AND (head OR neck). Data for all patients were recorded when available, including age, sex, localization, histological grading, treatment, possible recurrence, and outcome. A total of 83 published studies were identified through PubMed, Google Scholar, and Scopus databases, together with additional references list searches from 1979 to date. A total of 49 papers were excluded, and 34 manuscripts were considered for this systematic review, including 213 patients. We also reported a case of a 45-year-old male with an extracranial neck psammomatous meningioma with sizes of 4 cm × 3 cm × 2 cm. Furthermore, whole-body 68Ga-DOTATOC PET/CT was performed, excluding tumor spread to other areas. Surgical resection of the tumor was accomplished, as well as skin flap reconstruction, obtaining radical removal and satisfying wound healing. PEMs could suggest an infiltrative and aggressive behavior, which has never found a histopathological correlation with a malignancy (low Ki-67, <5%). Whole-body 68Ga-DOTATOC PET/CT should be considered in the patient’s global assessment. Surgical removal is a resolutive treatment, and the examination of frozen sections can confirm the benignity of the lesion, reducing the extension of the removal of healthy tissue surrounding the tumor.