bluuebunny/crossref_metadata_2025 huggingface dataset:
Nutrient Release through Litterfall in Short Rotation Poplar Crops in Mediterranean Marginal Land
Authors: Pérez Paloma , Barro Ruth , Pérez Javier , Fernández Miguel J. , Moyano Amelia , Ciria Pilar
Published: September 2021

A detailed knowledge of how poplar leaf litter decomposes under Mediterranean marginal conditions can help to minimize fertilization inputs and determine the profitability and sustainability of energy crops established in these particularly sensitive areas for bioenergy. Leaf litter decomposition was monitored for 32 months using the litterbag technique in a poplar crop under short rotation conditions in a marginal Mediterranean area. In addition, nutrient dynamics, together with the production and composition of the woody and foliar biomass produced, were studied for a period of four years. Leaf litter decomposition was relatively slow, particularly during the winter months, and accelerated in early spring, coinciding with the rainy season. At the end of the decomposition study 50% of the initial litterfall was decomposed, releasing roughly 60% of the N, 40% of the K, and 70% of the P initially present in fresh leaves. Annual yields of 6.0 dry Mg ha−1 were obtained. The aerial biomass produced the first year of the second rotation cycle extracted 83, 8.7, and 29 kg ha−1 of N, P, and K, respectively, whereas the amount of nutrients that were estimated to be naturally supplied to the system through leaf litter decomposition were 180 kg ha−1 of N, 19 kg ha−1 of P, and 30 kg ha−1 of K. Therefore, four years after establishing the energy crop, leaf litter was able to release higher amounts of primary macronutrients into the environment than the nutrient uptake by the produced aboveground biomass (woody and foliar biomass).
N6-Methyladenosine-Related lncRNA Signature Predicts the Overall Survival of Colorectal Cancer Patients
Authors: Song Wei , Ren Jun , Yuan Wenzheng , Xiang Rensheng , Ge Yuhang , Fu Tao
Published: September 2021

Background: The N6-methyladenosine (m6A) RNA modification can modify long non-coding RNAs (lncRNAs), thereby affecting the tumorigenesis and progression of tumors. However, the underlying role of m6A-modified lncRNAs in colorectal cancer (CRC) remains largely unknown. Therefore, our aim was to assess the prognostic value of m6A-modified lncRNAs in CRC patients. Methods: The gene expression and clinicopathological data of CRC were extracted from The Cancer Genome Atlas (TCGA) database. Pearson correlation analysis was used to investigate the m6A-modified lncRNAs. Consensus clustering was conducted to identify molecular subtypes of CRC, and the clinical significance of molecular subtypes was identified. The least absolute shrinkage and selection operator analysis (LASSO) was applied to establish a risk signature. Finally, a prognostic nomogram with risk score and clinicopathological variables was established. Results: In total, 29 m6A-modified lncRNAs were identified as prognostic lncRNAs. Two molecular clusters were identified and significant differences were found with respect to clinicopathological features and prognosis. Cluster1 is associated with poor overall survival (OS), down-regulation of Programmed cell death ligand-1 (PD-L1) expression, lower immune score, and less immune cell infiltration. Then, an m6A-modified lncRNA signature for predicting OS was constructed in the TCGA training cohort. The signature demonstrated favorable prediction performance in both training and validation sets. Compared with low-risk patients, patients with high risk showed worse clinical outcomes, lower immune scores, and downregulated PD-L1 expression. Further analysis indicated that the signature was an independent prognostic indicator, and then a prognostic nomogram based on risk score, tumor location, and tumor stage was established. Conclusions: Our study identified a seven m6A-modified lncRNA signature and established a prognostic nomogram that reliably predicts OS in CRC. These findings may improve the understanding of m6A modifications in CRC and provide insights into the prognosis and treatment strategy of CRC.
Single Nucleotide Polymorphisms of Immunity-Related Genes and Their Effects on Immunophenotypes in Different Pig Breeds
Authors: Chen Ann Ying-An , Huang Chao-Wei , Liu Shyh-Hwa , Liu An-Chi , Chaung Hso-Chi
Published: September 2021

Enhancing resistance and tolerance to pathogens remains an important selection objective in the production of livestock animals. Single nucleotide polymorphisms (SNPs) vary gene expression at the transcriptional level, influencing an individual’s immune regulation and susceptibility to diseases. In this study, we investigated the distribution of SNP sites in immune-related genes and their correlations with cell surface markers of immune cells within purebred (Taiwan black, Duroc, Landrace and Yorkshire) and crossbred (Landrace-Yorkshire) pigs. Thirty-nine SNPs of immune-related genes, including 11 cytokines, 5 chemokines and 23 Toll-like receptors (TLRs) (interferon-α and γ (IFN-α, γ), tumor necrosis factor-α (TNF-α), granulocyte-macrophage colony-stimulating factor (GM-CSF), Monocyte chemoattractant protein-1 (MCP-1) and TLR3, TLR4, TLR7, TLR8, and TLR9) were selected, and the percentages of positive cells with five cell surface markers of CD4, CD8, CD80/86, MHCI, and MHCII were analyzed. There were 28 SNPs that were significantly different among breeds, particularly between Landrace and Taiwan black. For instance, the frequency of SNP1 IFN-α -235A/G in Taiwan black and Landrace was 11.11% and 96.15%, respectively. In addition, 18 SNPs significantly correlated with the expression of cell surface markers, including CD4, CD8, CD80/86, and MHCII. The percentage of CD4+ (39.27%) in SNP33 TLR-8 543C/C was significantly higher than those in A/C (24.34%), at p < 0.05. Together, our findings show that Taiwan black pigs had a unique genotype distribution, whereas Landrace and Yorkshire had a more similar genotype distribution. Thus, an understanding of the genetic uniqueness of each breed could help to identify functionally important SNPs in immunoregulation.
Genetic Spectrum and Characteristics of Hereditary Optic Neuropathy in Taiwan
Authors: Lin Chao-Wen , Huang Ching-Wen , Luo Allen Chilun , Chou Yuh-Tsyr , Huang Yu-Shu , Chen Pei-Lung , Chen Ta-Ching
Published: September 2021

Hereditary optic neuropathy (HON) is a group of genetically heterogeneous diseases that cause optic nerve atrophy and lead to substantial visual impairment. HON may present with optic nerve atrophy only or in association with various systemic abnormalities. Although a genetic survey is indispensable for diagnosing HON, conventional sequencing techniques could render its diagnosis challenging. In this study, we attempted to explore the genetic background of patients with HON in Taiwan through capture-based next-generation sequencing targeting 52 HON-related genes. In total, 57 patients from 48 families were recruited, with 6 patients diagnosed as having Leber hereditary optic neuropathy through initial screening for three common variants (m.3460G>A, m.11778G>A, m.14484T>C). Disease-causing genotypes were identified in 14 (33.3%) probands, and OPA1 variants were the most prevalent cause of autosomal HON. Exposure to medications such as ethambutol could trigger an attack of autosomal dominant optic atrophy. WFS1 variants were identified in three probands with variable clinical features in our cohort. Hearing impairment could occur in patients with OPA1 or WFS1 variants. This is the first comprehensive study investigating the genetic characteristics of HON in Taiwan, especially for autosomal HON. Our results could provide useful information for clinical diagnosis and genetic counseling in this field.
GLUT1 Deficiency Syndrome—Early Treatment Maintains Cognitive Development? (Literature Review and Case Report)
Authors: Kolic Ivana , Radic Nisevic Jelena , Vlasic Cicvaric Inge , Butorac Ahel Ivona , Lah Tomulic Kristina , Segulja Silvije , Baraba Dekanic Kristina , Serifi Senada , Ovuka Aleksandar , Prpic Igor
Published: September 2021

Glucose transporter type 1 (GLUT1) is the most important energy carrier of the brain across the blood–brain barrier, and a genetic defect of GLUT1 is known as GLUT1 deficiency syndrome (GLUT1DS). It is characterized by early infantile seizures, developmental delay, microcephaly, ataxia, and various paroxysmal neurological phenomena. In most cases, GLUT1DS is caused by heterozygous single-nucleotide variants (SNVs) in the SLC2A1 gene that provoke complete or severe impairment of the functionality and/or expression of GLUT1 in the brain. Despite the rarity of these diseases, GLUT1DS is of high clinical interest since a very effective therapy, the ketogenic diet, can improve or reverse symptoms, especially if it is started as early as possible. We present a clinical phenotype, biochemical analysis, electroencephalographic and neuropsychological features of an 11-month-old boy with myoclonic seizures, hypogammaglobulinemia, and mildly impaired gross motor development. Using sequence analysis and deletion/duplication testing, deletion of an entire coding sequence in the SLC2A1 gene was detected. Early introduction of a modified Atkins diet maintained a seizure-free period without antiseizure medications and normal cognitive development in the follow-up period. Our report summarizes the clinical features of GLUT1 syndromes and discusses the importance of early identification and molecular confirmation of GLUT1DS as a treatable metabolic disorder.
No Expression Divergence despite Transcriptional Interference between Nested Protein-Coding Genes in Mammals
Authors: Assis Raquel
Published: September 2021

Nested protein-coding genes accumulated throughout metazoan evolution, with early analyses of human and Drosophila microarray data indicating that this phenomenon was simply due to the presence of large introns. However, a recent study employing RNA-seq data uncovered evidence of transcriptional interference driving rapid expression divergence between Drosophila nested genes, illustrating that accurate expression estimation of overlapping genes can enhance detection of their relationships. Hence, here I apply an analogous approach to strand-specific RNA-seq data from human and mouse to revisit the role of transcriptional interference in the evolution of mammalian nested genes. A genomic survey reveals that whereas mammalian nested genes indeed accrued over evolutionary time, they are retained at lower frequencies than in Drosophila. Though several properties of mammalian nested genes align with observations in Drosophila and with expectations under transcriptional interference, contrary to both, their expression divergence is not statistically different from that between unnested genes, and also does not increase after nesting. Together, these results support the hypothesis that lower selection efficiencies limit rates of gene expression evolution in mammals, leading to their reliance on immediate eradication of deleterious nested genes to avoid transcriptional interference.
An Age Scale for the First Shallow (Sub-)Antarctic Ice Core from Young Island, Northwest Ross Sea
Authors: Moser Dorothea Elisabeth , Jackson Sarah , Kjær Helle Astrid , Markle Bradley , Ngoumtsa Estelle , Pedro Joel B. , Segato Delia , Spolaor Andrea , Tetzner Dieter , Vallelonga Paul , Thomas Elizabeth R.
Published: September 2021

The climate of the sub-Antarctic is important in understanding the environmental conditions of Antarctica and the Southern Ocean. However, regional climate proxy records from this region are scarce. In this study, we present the stable water isotopes, major ion chemistry, and dust records from the first ice core from the (sub-)Antarctic Young Island. We present and discuss various dating approaches based on commonly used ice core proxies, such as stable water isotopes and seasonally deposited ions, together with site-specific characteristics such as melt layers. The dating approaches are compared with estimated precipitation rates from reanalysis data (ERA5) and volcanic cryptotephra shards likely presenting an absolute tie point from a 2001 CE eruption on neighboring Sturge Island. The resulting ice core age scale spans the period 2016 to 1995, with an uncertainty of ±2 years.
Two Shades of Cringe: Problems in Attributing Painful Laughter
Authors: Wöhrle Patrick
Published: September 2021

This article aims to approach the phenomenon of cringe in four steps: First, from a sociological perspective, the distinction between shame and embarrassment is discussed and a working definition is developed that conceives of this difference as situational rather than essential. In a second step, this distinction will be used to examine more closely how the actors’ self-representation is decomposed in the reality format Wife Swap and what role cringe—understood as “Fremdscham” or “vicarious embarrassment”—plays in this. Third, an explanation for the attractiveness of these formats is offered that draws on the concept of “flexible normalism” and further specifies the latent functions of these formats sociologically. Finally, with a look at current cringe comedy, it is elaborated that the use of cringe as made in Wife Swap is a very restricted and truncated variety of this phenomenon. Cringe in a comprehensive sense, meanwhile, turns out to be a reflexive resource based on an unresolved ambiguity of multiple and often intersecting attributions.
Overcoming Obstacles to Develop High-Performance Teams Involving Physician in Health Care Organizations
Authors: Rabkin Simon W. , Frein Mark
Published: September 2021

Many health care organizations struggle and often do not succeed to be high-performance organizations that are not only efficient and effective but also enjoyable places to work. This review focuses on the physician and organizational roles in limiting achievement of a high-performance team in health care organizations. Ten dimensions were constructed and a number of competencies and metrics were highlighted to overcome the failures to: (i) Ensure that the goals, purpose, mission and vision are clearly defined; (ii) establish a supportive organizational structure that encourages high performance of teams; (iii) ensure outstanding physician leadership, performance, goal attainment; and (iv) recognize that medical team leaders are vulnerable to the abuses of personal power or may create a culture of intimidation/fear and a toxic work culture; (v) select a good team and team members—team members who like to work in teams or are willing and able to learn how to work in a team and ensure a well-balanced team composition; (vi) establish optimal team composition, individual roles and dynamics, and clear roles for members of the team; (vii) establish psychological safe environment for team members; (viii) address and resolve interpersonal conflicts in teams; (xi) ensure good health and well-being of the medical staff; (x) ensure physician engagement with the organization. Addressing each of these dimensions with the specific solutions outlined should overcome the constraints to achieving high-performance teams for physicians in health care organizations.
The New ISO/IEC Standard for Automated ECG Interpretation
Authors: Young Brian , Schmid Johann-Jakob
Published: September 2021

Updates to industry consensus standards for ECG equipment is a work-in-progress by the ISO/IEC Joint Work Group 22. This work will result in an overhaul of existing industry standards that apply to ECG electromedical equipment and will result in a new single international industry, namely 80601-2-86. The new standard will be entitled “80601, Part 2-86: Particular requirements for the basic safety and essential performance of electrocardiographs, including diagnostic equipment, monitoring equipment, ambulatory equipment, electrodes, cables, and leadwires”. This paper will provide a high-level overview of the work in progress and, in particular, will describe the impact it will have on requirements and testing methods for computerized ECG interpretation algorithms. The conclusion of this work is that manufacturers should continue working with clinical ECG experts to make clinically meaningful improvements to automated ECG interpretation, and the clinical validation of ECG analysis algorithms should be disclosed to guide appropriate clinical use. More cooperation is needed between industry, clinical ECG experts and regulatory agencies to develop new data sets that can be made available for use by industry standards for algorithm performance evaluation.
A Review on Historical Earth Pigments Used in India’s Wall Paintings
Authors: Sharma Anjali , Singh Manager Rajdeo
Published: September 2021

Iron-containing earth minerals of various hues were the earliest pigments of the prehistoric artists who dwelled in caves. Being a prominent part of human expression through art, nature-derived pigments have been used in continuum through ages until now. Studies reveal that the primitive artist stored or used his pigments as color cakes made out of skin or reeds. Although records to help understand the technical details of Indian painting in the early periodare scanty, there is a certain amount of material from which some idea may be gained regarding the methods used by the artists to obtain their results. Considering Indian wall paintings, the most widely used earth pigments include red, yellow, and green ochres, making it fairly easy for the modern era scientific conservators and researchers to study them. The present knowledge on material sources given in the literature is limited and deficient as of now, hence the present work attempts to elucidate the range of earth pigments encountered in Indian wall paintings and the scientific studies and characterization by analytical techniques that form the knowledge background on the topic. Studies leadingto well-founded knowledge on pigments can contribute towards the safeguarding of Indian cultural heritage as well as spread awareness among conservators, restorers, and scholars.
Estrogen and Progesterone Receptor Immunoexpression in Fallopian Tubes among Postmenopausal Women Based on Time since the Last Menstrual Period
Authors: Brodowska Agnieszka , Grabowska Marta , Bittel Katarzyna , Ciećwież Sylwester , Brodowski Jacek , Szczuko Małgorzata , Szydłowska Iwona , Piasecka Małgorzata
Published: September 2021

Existing data on the expression of estrogen receptor (ERα) and progesterone receptor (PR) in fallopian tubes in postmenopausal women are mostly inconclusive. Therefore, we assessed ERα and PR immunoexpression in the oviducts of these women. One hundred postmenopausal women were divided into three groups based on time elapsed since the last menstrual period: (A) 1–5 years, (B) 6–10 years, and (C) ≥11 years. In all groups, both in the glandular epithelium and stroma of the ampulla and isthmus of the oviduct, immunolocalization of ERα and PR were noted. The glandular epithelium of the ampulla showed a higher percentage of PR-positive cells than the isthmus in each group. Regarding ERα, there were no significant differences. In the glandular epithelium in both the ampulla and isthmus, the percentage of ERα- and PR-positive cells was significantly higher than that in the stroma in each study group and higher in the A group than in the C group. In conclusion, in postmenopausal women, time elapsed since the last menstrual period in the fallopian tubes was positively correlated with the following: (1) the epithelium showed vacuolation of cytoplasm with greater frequency, (2) the proportion of ciliated cells decreased, and (3) the percentage of ERα- and PR-positive cells also decreased. The obtained results indicate a significant decrease in ERα and PR expression depending on the time that has elapsed since the last menstruation, which is undoubtedly related to the loss of the reproductive function of the patients.
Correlates of Levels of Willingness to Engage in Climate Change Actions in the United States
Authors: Latkin Carl A. , Dayton Lauren , Lee Da-In , Yi Grace , Uzzi Mudia
Published: September 2021

While the majority of the American public believe climate change is occurring and are worried, few are engaged in climate change action. In this study, we assessed factors associated with the level of willingness to engage in climate change actions using an online, longitudinal US study of adults. Climate change action outcomes included the level of willingness to post materials online, take political actions, talk with peers about climate change, and donate to or help an organization. Predictors included climate change attitudes, environmental attitudes, political ideology, political party affiliation, and demographic variables. Most (72%) of the 644 respondents only talked about climate change with peers a few times a year or less, though 65% were very or extremely worried about climate change. Many respondents indicated a willingness to do somewhat or a lot more, from 38% willing to talk to peers to 25% for willing to take political actions. In multinomial regression models, the Climate Change Concern scale was strongly and consistently associated with willingness to engage in climate change action. These findings indicate a need to both identify those who are willing to act and finding activities that fit with their interests and availability.
Change of Consumption Behaviours in the Pandemic of COVID-19: Examining Residents’ Consumption Expenditure and Driving Determinants
Authors: Xiong Jimin , Tang Zhanfeng , Zhu Yufeng , Xu Kefeng , Yin Yanhong , Xi Yang
Published: September 2021

This study investigated changes of individuals’ consumption behaviours during the COVID-19 pandemic and explored the driving determinants in consumption expenditure in Zhejiang China. Based on the 454 samples of survey data, which were collected in 2020 and 2021, it showed a reduction trend in consumption expenditure during the pandemic. Compared to the consumptions before the pandemic, money spent on housing, food, and beverage did not change too much. However, expenditures on wearing, recreation, and education reduced. Age, family size, and household income were significant to the expenditure changes. Online shopping became an important alternative way for residents during the pandemic and the trend is expected to continue even after the pandemic. Based on the findings, suggestions are summarized as two points. First, the young and single residents are the main group for recovering the consumption for wearing, recreation, education, and public transport. Meanwhile, to improve the satisfactions in online shopping, regulations should be issued by the government in improving the quality of goods and service.
To Vaccinate or Not to Vaccinate—This Is the Question among Swiss University Students
Authors: Dratva Julia , Wagner Aylin , Zysset Annina , Volken Thomas
Published: September 2021

The speed and innovation of the COVID-19 vaccine development has been accompanied by insecurity and skepticism. Young adults’ attitude to vaccination remains under investigation, although herd immunity cannot be reached without them. The HEalth in Students during the Corona pandemic study (HES-C) provided the opportunity to investigate vaccination intention in 1478 students in the sixth survey wave (January 2021), including vaccination intention, psychological antecedents of vaccine hesitancy, trust in government’s vaccination strategy, and vaccination history. Associations with vaccination intention were analyzed with multivariate ordinal regression and predicted margins were calculated adjusting for gender, age, anxiety, health profession, and subjective health status. A third was decided (yes 25.1%, no 7.6%), and 68% were unsure about getting the COVID-19 vaccine when available. Next to demographic characteristics, vaccination history (influenza vaccination OR = 1.39; 95% CI: 1.06–1.83, travel vaccination OR = 1.29; 95% CI: 1.04–1.60), trust in vaccination strategy (OR = 2.40; 95% CI: 1.89–3.05), and 5C dimensions were associated with vaccination intention: confidence (OR = 2.52; 95% CI: 2.09–3.03), complacency (OR = 0.79; 95% CI: 0.66–0.96), calculation (OR = 0.79; 95% CI: 0.70–0.89), constraints (OR = 1.18; 95% CI: 0.99–1.41), and collective responsibility (OR = 4.47; 95% CI: 3.69–5.40). Addressing psychological antecedents and strengthening trust in official strategies through targeted campaigns and interventions may increase decisiveness and result in higher vaccination rates.
Combined Multimorbidity and Polypharmacy Patterns in the Elderly: A Cross-Sectional Study in Primary Health Care
Authors: Stafford Grant , Villén Noemí , Roso-Llorach Albert , Troncoso-Mariño Amelia , Monteagudo Mònica , Violán Concepción
Published: September 2021

(1) Background: The acquisition of multiple chronic diseases, known as multimorbidity, is common in the elderly population, and it is often treated with the simultaneous consumption of several prescription drugs, known as polypharmacy. These two concepts are inherently related and cause an undue burden on the individual. The aim of this study was to identify combined multimorbidity and polypharmacy patterns for the elderly population in Catalonia. (2) Methods: A cross-sectional study using electronic health records from 2012 was conducted. A mapping process was performed linking chronic disease categories to the drug categories indicated for their treatment. A soft clustering technique was then carried out on the final mapped categories. (3) Results: 916,619 individuals were included, with 93.1% meeting the authors’ criteria for multimorbidity and 49.9% for polypharmacy. A seven-cluster solution was identified: one non-specific (Cluster 1) and six specific, corresponding to diabetes (Cluster 2), neurological and musculoskeletal, female dominant (Clusters 3 and 4) and cardiovascular, cerebrovascular and renal diseases (Clusters 5 and 6), and multi-system diseases (Cluster 7). (4) Conclusions: This study utilized a mapping process combined with a soft clustering technique to determine combined patterns of multimorbidity and polypharmacy in the elderly population, identifying overrepresentation in six of the seven clusters with chronic disease and chronic disease-drug categories. These results could be applied to clinical practice guidelines in order to better attend to patient needs. This study can serve as the foundation for future longitudinal regarding relationships between multimorbidity and polypharmacy.
COVID-19: A Cross-Sectional Study of Healthcare Students’ Perceptions of Life during the Pandemic in the United States and Brazil
Authors: Geer Laura A. , Radigan Rachel , Bruneli Guilherme de Lima , Leite Lucas Sampaio , Belian Rosalie Barreto
Published: September 2021

Societal influences, such as beliefs and behaviors, and their increasing complexity add to the challenges of interactivity promoted by globalization. This study was developed during a virtual global educational exchange experience and designed for research and educational purposes to assess personal social and cultural risk factors for students’ COVID-19 personal prevention behavior and perceptions about life during the pandemic, and to inform future educational efforts in intercultural learning for healthcare students. We designed and implemented a cross-sectional anonymous online survey intended to assess social and cultural risk factors for COVID-19 personal prevention behavior and students’ perceptions about life during the pandemic in public health and healthcare students in two public universities (United States n = 53; Brazil n = 55). Statistically significant differences existed between the United States and Brazil students in degree type, employment, risk behavior, personal prevention procedures, sanitization perceptions, and views of governmental policies. Cultural and social differences, risk messaging, and lifestyle factors may contribute to disparities in perceptions and behaviors of students around the novel infectious disease, with implications for future global infectious disease control.
School Teachers’ Self-Reported Fear and Risk Perception during the COVID-19 Pandemic—A Nationwide Survey in Germany
Authors: Weinert Stefanie , Thronicke Anja , Hinse Maximilian , Schad Friedemann , Matthes Harald
Published: September 2021

With the coronavirus disease 2019 (COVID-19) cases peaking and health systems reaching their limits in winter 2020/21, schools remained closed in many countries. To better understand teachers’ risk perception, we conducted a survey in Germany. Participants were recruited through various associations and invited to take part in a cross-sectional COVID-19-specific online survey. Descriptive statistical analysis was performed. Factors associated with teachers’ fears of contracting the severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) were evaluated with an adjusted multivariable regression analysis. The median age of the 6753 participating teachers was 43 years, and 77% were female. Most teachers worked in high schools (29%) and elementary schools (26%). The majority of participants (73%) feared contracting SARS-CoV-2 at school, while 77% intended to receive their COVID-19 vaccination. Ninety-eight percent considered students to pose the greatest risk. Female and younger teachers were significantly more anxious to get infected and teachers who opposed the re-opening of schools had significantly higher odds of being more anxious (p < 0.001). To the authors’ knowledge, this is the first study to describe teachers’ risk perception of COVID-19 and their attitudes towards vaccinations in a nationwide survey. The anxiety correlates with the COVID-19 protection measures demanded and appears to be a driving factor rather than rational logic.
Factors Associated with the Maintenance of Breastfeeding at One Year among Women in Chiang Mai, Thailand
Authors: Ongprasert Krongporn , Siviroj Penprapa
Published: September 2021

This study aimed to investigate factors associated with breastfeeding for at least one year among women in Chiang Mai, Thailand. We conducted a cross-sectional study of 451 mothers with children aged between 12 and 24 months who visited the well-baby clinic among women who visited the well-baby clinic in secondary and tertiary hospitals. The data collected included maternal sociodemographic information, employment status, reasons contributing to continued breastfeeding, primary sources of information, and influential people affecting continued breastfeeding. Multivariable logistic regression analysis was used to investigate the relationship between explanatory variables and continued breastfeeding at one year. Reporting “easier to bond with baby” as a reason to continue breastfeeding (AOR 3.118, 95% CI: 2.022, 4.809) and multiparous status (AOR 1.588, 95% CI: 1.042, 2.420) were positive predictors of mothers who had breastfeeding at least one year postpartum while mothers with undergraduate education level (AOR 0.635, 95% CI: 0.404, 0.997) were more likely to discontinue breastfeeding. Our study highlighted that working mothers have lower odds of continued breastfeeding than stay-at-home mothers (SAHMs), which was found for work with day shifts (AOR 0.437, 95% CI: 0.261, 0.731), work with rotational shifts (AOR 0.481, 95% CI: 0.247, 0.934), and work from home jobs with a flexible schedule (AOR 0.439, 95% CI: 0.229, 0.838). These findings showed that both employment outside home and work from home were strong risk factors for discontinuing breastfeeding before 12 months. We suggest that a breastfeeding-friendly workplace policy is essential to enhance the continuance of breastfeeding. Additionally, working at home requires more research to explore breastfeeding barriers and establish more support strategies.
Human IPSC-Derived Model to Study Myelin Disruption
Authors: Chesnut Megan , Paschoud Hélène , Repond Cendrine , Smirnova Lena , Hartung Thomas , Zurich Marie-Gabrielle , Hogberg Helena T. , Pamies David
Published: September 2021

Myelin is of vital importance to the central nervous system and its disruption is related to a large number of both neurodevelopmental and neurodegenerative diseases. The differences observed between human and rodent oligodendrocytes make animals inadequate for modeling these diseases. Although developing human in vitro models for oligodendrocytes and myelinated axons has been a great challenge, 3D cell cultures derived from iPSC are now available and able to partially reproduce the myelination process. We have previously developed a human iPSC-derived 3D brain organoid model (also called BrainSpheres) that contains a high percentage of myelinated axons and is highly reproducible. Here, we have further refined this technology by applying multiple readouts to study myelination disruption. Myelin was assessed by quantifying immunostaining/confocal microscopy of co-localized myelin basic protein (MBP) with neurofilament proteins as well as proteolipid protein 1 (PLP1). Levels of PLP1 were also assessed by Western blot. We identified compounds capable of inducing developmental neurotoxicity by disrupting myelin in a systematic review to evaluate the relevance of our BrainSphere model for the study of the myelination/demyelination processes. Results demonstrated that the positive reference compound (cuprizone) and two of the three potential myelin disruptors tested (Bisphenol A, Tris(1,3-dichloro-2-propyl) phosphate, but not methyl mercury) decreased myelination, while ibuprofen (negative control) had no effect. Here, we define a methodology that allows quantification of myelin disruption and provides reference compounds for chemical-induced myelin disruption.
Oral Squamous Cell Carcinoma Contributes to Differentiation of Monocyte-Derived Tumor-Associated Macrophages via PAI-1 and IL-8 Production
Authors: Kai Kazuki , Moriyama Masafumi , Haque A. S. M. Rafiul , Hattori Taichi , Chinju Akira , Hu Chen , Kubota Keigo , Miyahara Yuka , Kakizoe-Ishiguro Noriko , Kawano Shintaro , Nakamura Seiji
Published: September 2021

Tumor-associated macrophages (TAMs) promote cancer cell proliferation and metastasis, as well as anti-tumor immune suppression. Recent studies have shown that tumors enhance the recruitment and differentiation of TAMs, but the detailed mechanisms have not been clarified. We thus examined the influence of cancer cells on the differentiation of monocytes to TAM subsets, including CD163+, CD204+, and CD206+ cells, in oral squamous cell carcinoma (OSCC) using immunohistochemistry, flow cytometry, and a cytokine array. Furthermore, we investigated the effect of OSCC cells (HSC-2, SQUU-A, and SQUU-B cells) on the differentiation of purified CD14+ cells to TAM subsets. The localization patterns of CD163+, CD204+, and CD206+ in OSCC sections were quite different. The expression of CD206 on CD14+ cells was significantly increased after the co-culture with OSCC cell lines, while the expressions of CD163 and CD204 on CD14+ cells showed no change. High concentrations of plasminogen activator inhibitor-1 (PAI-1) and interleukin-8 (IL-8) were detected in the conditioned medium of OSCC cell lines. PAI-1 and IL-8 stimulated CD14+ cells to express CD206. Moreover, there were positive correlations among the numbers of CD206+, PAI-1+, and IL-8+ cells in OSCC sections. These results suggest that PAI-1 and IL-8 produced by OSCC contribute to the differentiation of monocytes to CD206+ TAMs.
Ixodes ricinus Salivary Serpin Iripin-8 Inhibits the Intrinsic Pathway of Coagulation and Complement
Authors: Kotál Jan , Polderdijk Stéphanie G. I. , Langhansová Helena , Ederová Monika , Martins Larissa A. , Beránková Zuzana , Chlastáková Adéla , Hajdušek Ondřej , Kotsyfakis Michail , Huntington James A. , Chmelař Jindřich
Published: September 2021

Tick saliva is a rich source of antihemostatic, anti-inflammatory, and immunomodulatory molecules that actively help the tick to finish its blood meal. Moreover, these molecules facilitate the transmission of tick-borne pathogens. Here we present the functional and structural characterization of Iripin-8, a salivary serpin from the tick Ixodes ricinus, a European vector of tick-borne encephalitis and Lyme disease. Iripin-8 displayed blood-meal-induced mRNA expression that peaked in nymphs and the salivary glands of adult females. Iripin-8 inhibited multiple proteases involved in blood coagulation and blocked the intrinsic and common pathways of the coagulation cascade in vitro. Moreover, Iripin-8 inhibited erythrocyte lysis by complement, and Iripin-8 knockdown by RNA interference in tick nymphs delayed the feeding time. Finally, we resolved the crystal structure of Iripin-8 at 1.89 Å resolution to reveal an unusually long and rigid reactive center loop that is conserved in several tick species. The P1 Arg residue is held in place distant from the serpin body by a conserved poly-Pro element on the P′ side. Several PEG molecules bind to Iripin-8, including one in a deep cavity, perhaps indicating the presence of a small-molecule binding site. This is the first crystal structure of a tick serpin in the native state, and Iripin-8 is a tick serpin with a conserved reactive center loop that possesses antihemostatic activity that may mediate interference with host innate immunity.
AMPK Phosphorylation Is Controlled by Glucose Transport Rate in a PKA-Independent Manner
Authors: Milanesi Riccardo , Tripodi Farida , Vertemara Jacopo , Tisi Renata , Coccetti Paola
Published: September 2021

To achieve growth, microbial organisms must cope with stresses and adapt to the environment, exploiting the available nutrients with the highest efficiency. In Saccharomyces cerevisiae, Ras/PKA and Snf1/AMPK pathways regulate cellular metabolism according to the supply of glucose, alternatively supporting fermentation or mitochondrial respiration. Many reports have highlighted crosstalk between these two pathways, even without providing a comprehensive mechanism of regulation. Here, we show that glucose-dependent inactivation of Snf1/AMPK is independent from the Ras/PKA pathway. Decoupling glucose uptake rate from glucose concentration, we highlight a strong coordination between glycolytic metabolism and Snf1/AMPK, with an inverse correlation between Snf1/AMPK phosphorylation state and glucose uptake rate, regardless of glucose concentration in the medium. Despite fructose-1,6-bisphosphate (F1,6BP) being proposed as a glycolytic flux sensor, we demonstrate that glucose-6-phosphate (G6P), and not F1,6BP, is involved in the control of Snf1/AMPK phosphorylation state. Altogether, this study supports a model by which Snf1/AMPK senses glucose flux independently from PKA activity, and thanks to conversion of glucose into G6P.
The Absence of Extracellular Cold-Inducible RNA-Binding Protein (eCIRP) Promotes Pro-Angiogenic Microenvironmental Conditions and Angiogenesis in Muscle Tissue Ischemia
Authors: Kübler Matthias , Beck Sebastian , Peffenköver Lisa Lilian , Götz Philipp , Ishikawa-Ankerhold Hellen , Preissner Klaus T. , Fischer Silvia , Lasch Manuel , Deindl Elisabeth
Published: September 2021

Extracellular Cold-inducible RNA-binding protein (eCIRP), a damage-associated molecular pattern, is released from cells upon hypoxia and cold-stress. The overall absence of extra- and intracellular CIRP is associated with increased angiogenesis, most likely induced through influencing leukocyte accumulation. The aim of the present study was to specifically characterize the role of eCIRP in ischemia-induced angiogenesis together with the associated leukocyte recruitment. For analyzing eCIRPs impact, we induced muscle ischemia via femoral artery ligation (FAL) in mice in the presence or absence of an anti-CIRP antibody and isolated the gastrocnemius muscle for immunohistological analyses. Upon eCIRP-depletion, mice showed increased capillary/muscle fiber ratio and numbers of proliferating endothelial cells (CD31+/CD45−/BrdU+). This was accompanied by a reduction of total leukocyte count (CD45+), neutrophils (MPO+), neutrophil extracellular traps (NETs) (MPO+CitH3+), apoptotic area (ascertained via TUNEL assay), and pro-inflammatory M1-like polarized macrophages (CD68+/MRC1−) in ischemic muscle tissue. Conversely, the number of regenerative M2-like polarized macrophages (CD68+/MRC1+) was elevated. Altogether, we observed that eCIRP depletion similarly affected angiogenesis and leukocyte recruitment as described for the overall absence of CIRP. Thus, we propose that eCIRP is mainly responsible for modulating angiogenesis via promoting pro-angiogenic microenvironmental conditions in muscle ischemia.
Astroglial Hemichannels and Pannexons: The Hidden Link between Maternal Inflammation and Neurological Disorders
Authors: Prieto-Villalobos Juan , Alvear Tanhia F. , Liberona Andrés , Lucero Claudia M. , Martínez-Araya Claudio J. , Balmazabal Javiera , Inostroza Carla A. , Ramírez Gigliola , Gómez Gonzalo I. , Orellana Juan A.
Published: September 2021

Maternal inflammation during pregnancy causes later-in-life alterations of the offspring’s brain structure and function. These abnormalities increase the risk of developing several psychiatric and neurological disorders, including schizophrenia, intellectual disability, bipolar disorder, autism spectrum disorder, microcephaly, and cerebral palsy. Here, we discuss how astrocytes might contribute to postnatal brain dysfunction following maternal inflammation, focusing on the signaling mediated by two families of plasma membrane channels: hemi-channels and pannexons. [Ca2+]i imbalance linked to the opening of astrocytic hemichannels and pannexons could disturb essential functions that sustain astrocytic survival and astrocyte-to-neuron support, including energy and redox homeostasis, uptake of K+ and glutamate, and the delivery of neurotrophic factors and energy-rich metabolites. Both phenomena could make neurons more susceptible to the harmful effect of prenatal inflammation and the experience of a second immune challenge during adulthood. On the other hand, maternal inflammation could cause excitotoxicity by producing the release of high amounts of gliotransmitters via astrocytic hemichannels/pannexons, eliciting further neuronal damage. Understanding how hemichannels and pannexons participate in maternal inflammation-induced brain abnormalities could be critical for developing pharmacological therapies against neurological disorders observed in the offspring.
A Reliable High-Throughput Screening Model for Antidepressant
Authors: Zhang Rui , Qiao Caili , Liu Qiuyan , He Jingwen , Lai Yifan , Shang Jing , Zhong Hui
Published: September 2021

Depression is the most frequent affective disorder and is the leading cause of disability worldwide. In order to screen antidepressants and explore molecular mechanisms, a variety of animal models were used in experiments, but there is no reliable high-throughput screening method. Zebrafish is a common model organism for mental illness such as depression. In our research, we established chronic unpredictable mild stress (CUMS) models in C57BL/6 mice and zebrafish; the similarities in behavior and pathology suggest that zebrafish can replace rodents as high-throughput screening organisms. Stress mice (ip., 1 mg/kg/d, 3 days) and zebrafish (10 mg/L, 20 min) were treated with reserpine. As a result, reserpine caused depression-like behavior in mice, which was consistent with the results of the CUMS mice model. Additionally, reserpine reduced the locomotor ability and exploratory behavior of zebrafish, which was consistent with the results of the CUMS zebrafish model. Further analysis of the metabolic differences showed that the reserpine-induced zebrafish depression model was similar to the reserpine mice model and the CUMS mice model in the tyrosine metabolism pathway. The above results showed that the reserpine-induced depression zebrafish model was similar to the CUMS model from phenotype to internal metabolic changes and can replace the CUMS model for antidepressants screening. Moreover, the results from this model were obtained in a short time, which can shorten the cycle of drug screening and achieve high-throughput screening. Therefore, we believe it is a reliable high-throughput screening model.
Isoleucilactucin Ameliorates Coal Fly Ash-Induced Inflammation through the NF-κB and MAPK Pathways in MH-S Cells
Authors: Ullah H. M. Arif , Kwon Tae-Hyung , Park SeonJu , Kim Sung Dae , Rhee Man Hee
Published: September 2021

We investigated whether isoleucilactucin, an active constituent of Ixeridium dentatum, reduces inflammation caused by coal fly ash (CFA) in alveolar macrophages (MH-S). The anti-inflammatory effects of isoleucilactucin were assessed by measuring the concentration of nitric oxide (NO) and the expression of pro-inflammatory mediators in MH-S cells exposed to CFA-induced inflammation. We found that isoleucilactucin reduced CFA-induced NO generation dose-dependently in MH-S cells. Moreover, isoleucilactucin suppressed CFA-activated proinflammatory mediators, including cyclooxygenase-2 (COX2) and inducible NO synthase (iNOS), and the proinflammatory cytokines such as interleukin-(IL)-1β, IL-6, and tumor necrosis factor (TNF-α). The inhibiting properties of isoleucilactucin on the nuclear translocation of phosphorylated nuclear factor-kappa B (p-NF-κB) were observed. The effects of isoleucilactucin on the NF-κB and mitogen-activated protein kinase (MAPK) pathways were also measured in CFA-stimulated MH-S cells. These results indicate that isoleucilactucin suppressed CFA-stimulated inflammation in MH-S cells by inhibiting the NF-κB and MAPK pathways, which suggest it might exert anti-inflammatory properties in the lung.
Neddylation Regulates Class IIa and III Histone Deacetylases to Mediate Myoblast Differentiation
Authors: Zhou Hongyi , Su Huabo , Chen Weiqin
Published: September 2021

As the largest tissue in the body, skeletal muscle has multiple functions in movement and energy metabolism. Skeletal myogenesis is controlled by a transcriptional cascade including a set of muscle regulatory factors (MRFs) that includes Myogenic Differentiation 1 (MYOD1), Myocyte Enhancer Factor 2 (MEF2), and Myogenin (MYOG), which direct the fusion of myogenic myoblasts into multinucleated myotubes. Neddylation is a posttranslational modification that covalently conjugates ubiquitin-like NEDD8 (neural precursor cell expressed, developmentally downregulated 8) to protein targets. Inhibition of neddylation impairs muscle differentiation; however, the underlying molecular mechanisms remain less explored. Here, we report that neddylation is temporally regulated during myoblast differentiation. Inhibition of neddylation through pharmacological blockade using MLN4924 (Pevonedistat) or genetic deletion of NEDD8 Activating Enzyme E1 Subunit 1 (NAE1), a subunit of the E1 neddylation-activating enzyme, blocks terminal myoblast differentiation partially through repressing MYOG expression. Mechanistically, we found that neddylation deficiency enhances the mRNA and protein expressions of class IIa histone deacetylases 4 and 5 (HDAC4 and 5) and prevents the downregulation and nuclear export of class III HDAC (NAD-Dependent Protein Deacetylase Sirtuin-1, SIRT1), all of which have been shown to repress MYOD1-mediated MYOG transcriptional activation. Together, our findings for the first time identify the crucial role of neddylation in mediating class IIa and III HDAC co-repressors to control myogenic program and provide new insights into the mechanisms of muscle disease and regeneration.