bluuebunny/crossref_metadata_2025 huggingface dataset:
INCULCATING CHARACTER EDUCATION USING ACHIEVEMENT BOARD MEDIA IN CLASS 3 THEMATIC LEARNING
Authors: Nur’aini Miftahul , Kamidjan Kamidjan , Raharja Hawwin Fitra
Published: March 2021

Education and schools that are expected to be able to make students well-behaved and smart in actual learning only focus on developing the cognitive knowledge of their students without being able to overcome the moral development of their students, this is evidenced by the many reports about juvenile delinquency that occur in Indonesia. So from these problems character education began to be carried out according to the 2003 SISDIKNAS Law. Given the lack of character of the nation's children, the task and responsibility of teachers is to inculcate character values early on into various activities in schools. Good learning must be supported by several aspects, namely processional teachers, the existence of learning resources and learning media. This research uses descriptive qualitative research methods with the type of field research. This study aims to describe the process of implementing character education planting using achievement board media in class 3 thematic learning at SDN Cukir 1. The use of achievement board media as character education planting in thematic learning can be applied through the following steps: Explaining the meaning and purpose of character education, introduce 18 character values, look for examples of behavior that reflect each value and introduce achievement board media and how to play them. Achievement board media have a positive impact such as lightening the task of the teacher, students are more active in learning, the values of characters are more striking in students, more easily understood and applied in student life
TAp63α Is Involved in Tobacco Smoke-Induced Lung Cancer EMT and the Anti-cancer Activity of Curcumin via miR-19 Transcriptional Suppression
Authors: Xie Chunfeng , Zhu Jianyun , Yang Xue , Huang Cong , Zhou Liping , Meng Zili , Li Xiaoting , Zhong Caiyun
Published: March 2021

As a key risk factor for lung cancer, tobacco smoke (TS) influences several cellular processes, including epithelial-mesenchymal transition (EMT). TAp63α is a crucial transcription factor involved in tumor progression. The present study was designed to investigate the potential role and underlying mechanisms of TAp63α in TS-induced lung cancer EMT. We found that compared to normal tissues, the tumor tissues collected from lung cancer patients showed a lower level of TAp63α expression, along with downregulated E-cadherin expression and upregulated Vimentin expression. Results of treatment with TAp63α and TAp63α siRNA as well as with tumor growth factor-β (TGF-β) showed that TAp63α acted as a tumor suppressor gene, and its upregulated expression suppressed lung cancer EMT. Significantly, TS exposure altered expression of EMT-related markers, enhanced cell migratory and invasive capacities, and decreased the TAp63α expression level in lung cancer cells. Overexpression of TAp63α significantly alleviated TS-stimulated lung cancer EMT. Mechanistically, TAp63α expression transcriptionally reduced the miR-19 level, which resulted in the suppression of lung cancer EMT. Additionally, as a natural compound possessing anti-cancer effects, curcumin inhibited TS-induced lung cancer EMT by increasing TAp63α expression and reducing miR-19 expression. Collectively, our results indicate that TAp63α inhibits TS-induced lung cancer EMT via transcriptionally suppressing miR-19 and the inhibitory effect of TAp63α on miR-19 mediates the anti-cancer action of curcumin. These findings provide new insights into novel targets for lung cancer prevention.
Vaginal Microbiota and Cytokine Levels Predict Preterm Delivery in Asian Women
Authors: Kumar Manoj , Murugesan Selvasankar , Singh Parul , Saadaoui Marwa , Elhag Duaa Ahmed , Terranegra Annalisa , Kabeer Basirudeen Syed Ahamed , Marr Alexandra K. , Kino Tomoshige , Brummaier Tobias , McGready Rose , Nosten François , Chaussabel Damien , Al Khodor Souhaila
Published: March 2021

Preterm birth (PTB) is the most common cause of neonatal morbidity and mortality worldwide. Approximately half of PTBs is linked with microbial etiologies, including pathologic changes to the vaginal microbiota, which vary according to ethnicity. Globally more than 50% of PTBs occur in Asia, but studies of the vaginal microbiome and its association with pregnancy outcomes in Asian women are lacking. This study aimed to longitudinally analyzed the vaginal microbiome and cytokine environment of 18 Karen and Burman pregnant women who delivered preterm and 36 matched controls delivering at full term. Using 16S ribosomal RNA gene sequencing we identified a predictive vaginal microbiota signature for PTB that was detectable as early as the first trimester of pregnancy, characterized by higher levels of Prevotella buccalis, and lower levels of Lactobacillus crispatus and Finegoldia, accompanied by decreased levels of cytokines including IFNγ, IL-4, and TNFα. Differences in the vaginal microbial diversity and local vaginal immune environment were associated with greater risk of preterm birth. Our findings highlight new opportunities to predict PTB in Asian women in low-resource settings who are at highest risk of adverse outcomes from unexpected PTB, as well as in Burman/Karen ethnic minority groups in high-resource regions.
HN-CNN: A Heterogeneous Network Based on Convolutional Neural Network for m7 G Site Disease Association Prediction
Authors: Zhang Lin , Chen Jin , Ma Jiani , Liu Hui
Published: March 2021

N7-methylguanosine (m7G) is a typical positively charged RNA modification, playing a vital role in transcriptional regulation. m7G can affect the biological processes of mRNA and tRNA and has associations with multiple diseases including cancers. Wet-lab experiments are cost and time ineffective for the identification of disease-related m7G sites. Thus, a heterogeneous network method based on Convolutional Neural Networks (HN-CNN) has been proposed to predict unknown associations between m7G sites and diseases. HN-CNN constructs a heterogeneous network with m7G site similarity, disease similarity, and disease-associated m7G sites to formulate features for m7G site-disease pairs. Next, a convolutional neural network (CNN) obtains multidimensional and irrelevant features prominently. Finally, XGBoost is adopted to predict the association between m7G sites and diseases. The performance of HN-CNN is compared with Naive Bayes (NB), Random Forest (RF), Support Vector Machine (SVM), as well as Gradient Boosting Decision Tree (GBDT) through 10-fold cross-validation. The average AUC of HN-CNN is 0.827, which is superior to others.
Immunological Considerations for Schistosoma Vaccine Development: Transitioning to Endemic Settings
Authors: Driciru Emmanuella , Koopman Jan Pieter R. , Cose Stephen , Siddiqui Afzal A. , Yazdanbakhsh Maria , Elliott Alison M. , Roestenberg Meta
Published: March 2021

Despite mass drug administration programmes with praziquantel, the prevalence of schistosomiasis remains high. A vaccine is urgently needed to control transmission of this debilitating disease. As some promising schistosomiasis vaccine candidates are moving through pre-clinical and clinical testing, we review the immunological challenges that these vaccine candidates may encounter in transitioning through the clinical trial phases in endemic settings. Prior exposure of the target population to schistosomes and other infections may impact vaccine response and efficacy and therefore requires considerable attention. Schistosomes are known for their potential to induce T-reg/IL-10 mediated immune suppression in populations which are chronically infected. Moreover, endemicity of schistosomiasis is focal whereby target and trial populations may exhibit several degrees of prior exposure as well asin uteroexposure which may increase heterogeneity of vaccine responses. The age dependent distribution of exposure and development of acquired immunity, and general differences in the baseline immunological profile, adds to the complexity of selecting suitable trial populations. Similarly, prior or concurrent infections with other parasitic helminths, viral and bacterial infections, may alter immunological responses. Consequently, treatment of co-infections may benefit the immunogenicity of vaccines and may be considered despite logistical challenges. On the other hand, viral infections leave a life-long immunological imprint on the human host. Screening for serostatus may be needed to facilitate interpretation of vaccine responses. Co-delivery of schistosome vaccines with PZQ is attractive from a perspective of implementation but may complicate the immunogenicity of schistosomiasis vaccines. Several studies have reported PZQ treatment to induce both transient and long-term immuno-modulatory effects as a result of tegument destruction, worm killing and subsequent exposure of worm antigens to the host immune system. These in turn may augment or antagonize vaccine immunogenicity. Understanding the complex immunological interactions between vaccine, co-infections or prior exposure is essential in early stages of clinical development to facilitate phase 3 clinical trial design and implementation policies. Besides well-designed studies in different target populations using schistosome candidate vaccines or other vaccines as models, controlled human infections could also help identify markers of immune protection in populations with different disease and immunological backgrounds.
Neutrophils in the Pathogenesis of Rheumatoid Arthritis and Systemic Lupus Erythematosus: Same Foe Different M.O.
Authors: Fresneda Alarcon Michele , McLaren Zoe , Wright Helen Louise
Published: March 2021

Dysregulated neutrophil activation contributes to the pathogenesis of autoimmune diseases including rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). Neutrophil-derived reactive oxygen species (ROS) and granule proteases are implicated in damage to and destruction of host tissues in both conditions (cartilage in RA, vascular tissue in SLE) and also in the pathogenic post-translational modification of DNA and proteins. Neutrophil-derived cytokines and chemokines regulate both the innate and adaptive immune responses in RA and SLE, and neutrophil extracellular traps (NETs) expose nuclear neoepitopes (citrullinated proteins in RA, double-stranded DNA and nuclear proteins in SLE) to the immune system, initiating the production of auto-antibodies (ACPA in RA, anti-dsDNA and anti-acetylated/methylated histones in SLE). Neutrophil apoptosis is dysregulated in both conditions: in RA, delayed apoptosis within synovial joints contributes to chronic inflammation, immune cell recruitment and prolonged release of proteolytic enzymes, whereas in SLE enhanced apoptosis leads to increased apoptotic burden associated with development of anti-nuclear auto-antibodies. An unbalanced energy metabolism in SLE and RA neutrophils contributes to the pathology of both diseases; increased hypoxia and glycolysis in RA drives neutrophil activation and NET production, whereas decreased redox capacity increases ROS-mediated damage in SLE. Neutrophil low-density granulocytes (LDGs), present in high numbers in the blood of both RA and SLE patients, have opposing phenotypes contributing to clinical manifestations of each disease. In this review we will describe the complex and contrasting phenotype of neutrophils and LDGs in RA and SLE and discuss their discrete roles in the pathogenesis of each condition. We will also review our current understanding of transcriptomic and metabolomic regulation of neutrophil phenotype in RA and SLE and discuss opportunities for therapeutic targeting of neutrophil activation in inflammatory auto-immune disease.
Roles of the Dynamic Tumor Immune Microenvironment in the Individualized Treatment of Advanced Clear Cell Renal Cell Carcinoma
Authors: Lin Enyu , Liu Xuechao , Liu Yanjun , Zhang Zedan , Xie Lu , Tian Kaiwen , Liu Jiumin , Yu Yuming
Published: March 2021

Immune checkpoint inhibitors (ICIs) are currently a first-line treatment option for clear cell renal cell carcinoma (ccRCC). However, recent clinical studies have shown that a large number of patients do not respond to ICIs. Moreover, only a few patients achieve a stable and durable response even with combination therapy based on ICIs. Available studies have concluded that the response to immunotherapy and targeted therapy in patients with ccRCC is affected by the tumor immune microenvironment (TIME), which can be manipulated by targeted therapy and tumor genomic characteristics. Therefore, an in-depth understanding of the dynamic nature of the TIME is important for improving the efficacy of immunotherapy or combination therapy in patients with advanced ccRCC. Here, we explore the possible mechanisms by which the TIME affects the efficacy of immunotherapy and targeted therapy, as well as the factors that drive dynamic changes in the TIME in ccRCC, including the immunomodulatory effect of targeted therapy and genomic changes. We also describe the progress on novel therapeutic modalities for advanced ccRCC based on the TIME. Overall, this review provides valuable information on the optimization of combination therapy and development of individualized therapy for advanced ccRCC.
Innovative Aquaculture for the Poor to Adjust to Environmental Change in Coastal Bangladesh? Barriers and Options for Progress
Authors: Selim Samiya Ahmed , Glaser Marion , Tacke Francheska Ilse , Rahman Mubashshira , Ahmed Nesar
Published: March 2021

More so than wealthier, less nature-dependent social groups, the poor in tropical coastal regions suffer from adverse environmental change and need new income options. With high levels of saltwater intrusion into coastal lands, innovative brackish water aquaculture (BWA) including integrated multi-trophic aquaculture (IMTA) are crucial adaptation options to the expanding marine waters. This article examines how poor Bangladeshi coastal residents view BWA, and what is needed to make BWA a viable and sustainable livelihood for the coastal poor. In sites that are affected by major salinity intrusion, we used a semi-structured questionnaire to interview 120 households. We examine three questions: (1) What kind of aquaculture is currently being undertaken in brackish/saline/coastal waters? (2) Do poor coastal residents see BWA (and, by implication the hitherto fairly unknown IMTA) as a viable and sustainable livelihood? (3) What is needed to make BWA a feasible and promising livelihood in Bangladesh? Our results show both information and perception biases obstruct in particular coastal poor women and men from engaging with innovative BWA. Their knowledge on ecosystem-based aquaculture was scarce and their views of aquaculture were related mainly to previous experiences with shrimp monoculture and its polarizing socio-economic effects. We propose some strategic fields of action to develop innovative BWA that also benefits coastal Bangladesh’s poorest people.
Speech Driven Gaze in a Face-to-Face Interaction
Authors: Arslan Aydin Ülkü , Kalkan Sinan , Acartürk Cengiz
Published: March 2021

Gaze and language are major pillars in multimodal communication. Gaze is a non-verbal mechanism that conveys crucial social signals in face-to-face conversation. However, compared to language, gaze has been less studied as a communication modality. The purpose of the present study is 2-fold: (i) to investigate gaze direction (i.e., aversion and face gaze) and its relation to speech in a face-to-face interaction; and (ii) to propose a computational model for multimodal communication, which predicts gaze direction using high-level speech features. Twenty-eight pairs of participants participated in data collection. The experimental setting was a mock job interview. The eye movements were recorded for both participants. The speech data were annotated by ISO 24617-2 Standard for Dialogue Act Annotation, as well as manual tags based on previous social gaze studies. A comparative analysis was conducted by Convolutional Neural Network (CNN) models that employed specific architectures, namely, VGGNet and ResNet. The results showed that the frequency and the duration of gaze differ significantly depending on the role of participant. Moreover, the ResNet models achieve higher than 70% accuracy in predicting gaze direction.
Inherited Metabolic Causes of Stroke in Children: Mechanisms, Types, and Management
Authors: Tabarki Brahim , Hakami Wejdan , Alkhuraish Nader , Graies-Tlili Kalthoum , Nashabat Marwan , Alfadhel Majid
Published: March 2021

A stroke should be considered in cases of neurologic decompensation associated with inherited metabolic disorders. A resultant stroke could be a classical ischemic stroke (vascular stroke) or more commonly a “metabolic stroke.” A metabolic stroke begins with metabolic dysfunctions, usually caused by a stressor, and leads to the rapid onset of prolonged central neurological deficits in the absence of vessel occlusion or rupture. The cardinal features of a metabolic stroke are stroke-like episodes without the confirmation of ischemia in the typical vascular territories, such as that seen in classic thrombotic or embolic strokes. Identifying the underlying cause of a metabolic stroke is essential for prompt and appropriate treatment. This study reviews the major inherited metabolic disorders that predispose patients to pediatric stroke, with an emphasis on the underlying mechanisms, types, and management.
Metastatic Spread in Prostate Cancer Patients Influencing Radiotherapy Response
Authors: Klusa Daria , Lohaus Fabian , Furesi Giulia , Rauner Martina , Benešová Martina , Krause Mechthild , Kurth Ina , Peitzsch Claudia
Published: March 2021

Radiotherapy and surgery are curative treatment options for localized prostate cancer (PCa) with a 5-year survival rate of nearly 100%. Once PCa cells spread into distant organs, such as bone, the overall survival rate of patients drops dramatically. The metastatic cascade and organotropism of PCa cells are regulated by different cellular subtypes, organ microenvironment, and their interactions. This cross-talk leads to pre-metastatic niche formation that releases chemo-attractive factors enforcing the formation of distant metastasis. Biological characteristics of PCa metastasis impacting on metastatic sites, burden, and latency is of clinical relevance. Therefore, the implementation of modern hybrid imaging technologies into clinical routine increased the sensitivity to detect metastases at earlier stages. This enlarged the number of PCa patients diagnosed with a limited number of metastases, summarized as oligometastatic disease. These patients can be treated with androgen deprivation in combination with local-ablative radiotherapy or radiopharmaceuticals directed to metastatic sites. Unfortunately, the number of patients with disease recurrence is high due to the enormous heterogeneity within the oligometastatic patient population and the lack of available biomarkers with predictive potential for metastasis-directed radiotherapy. Another, so far unmet clinical need is the diagnosis of minimal residual disease before onset of clinical manifestation and/or early relapse after initial therapy. Here, monitoring of circulating and disseminating tumor cells in PCa patients during the course of radiotherapy may give us novel insight into how metastatic spread is influenced by radiotherapy and vice versa. In summary, this review critically compares current clinical concepts for metastatic PCa patients and discuss the implementation of recent preclinical findings improving our understanding of metastatic dissemination and radiotherapy resistance into standard of care.
A Nomogram for Preoperative Estimation of Microvascular Invasion Risk in Hepatocellular Carcinoma: Single-Center Analyses With Internal Validation
Authors: Yang Jiarui , Zhu Shuguang , Yong Juanjuan , Xia Long , Qian Xiangjun , Yang Jiawei , Hu Xueqiao , Li Yuxuan , Wang Chusi , Peng Wenguang , Zhang Lei , Deng Meihai , Pan Weidong
Published: March 2021

Background

Microvascular invasion (MVI) is highly associated with poor prognosis in patients with liver cancer. Predicting MVI before surgery is helpful for surgeons to better make surgical plan. In this study, we aim at establishing a nomogram to preoperatively predict the occurrence of microvascular invasion in liver cancer.

Method

A total of 405 patients with postoperative pathological reports who underwent curative hepatocellular carcinoma resection in the Third Affiliated Hospital of Sun Yat-sen University from 2013 to 2015 were collected in this study. Among these patients, 290 were randomly assigned to the development group while others were assigned to the validation group. The MVI predictive factors were selected by Lasso regression analysis. Nomogram was established to preoperatively predict the MVI risk in HCC based on these predictive factors. The discrimination, calibration, and effectiveness of nomogram were evaluated by internal validation.

Results

Lasso regression analysis revealed that discomfort of right upper abdomen, vascular invasion, lymph node metastases, unclear tumor boundary, tumor necrosis, tumor size, higher alkaline phosphatase were predictive MVI factors in HCC. The nomogram was established with the value of AUROC 0.757 (0.716–0.809) and 0.768 (0.703–0.814) in the development and the validation groups. Well-fitted calibration was in both development and validation groups. Decision curve analysis confirmed that the predictive model provided more benefit than treat all or none patients. The predictive model demonstrated sensitivity of 58.7%, specificity of 80.7% at the cut-off value of 0.312.

Conclusion

Nomogram was established for predicting preoperative risk of MVI in HCC. Better treatment plans can be formulated according to the predicted results.
Identification and Validation of a Stromal EMT Related LncRNA Signature as a Potential Marker to Predict Bladder Cancer Outcome
Authors: Du YiHeng , Wang Bo , Jiang Xiang , Cao Jin , Yu Jiang , Wang Yi , Wang XiZhi , Liu HaiTao
Published: March 2021

Bladder cancer (BLCA) has become one of the most common malignant tumors in the genitourinary system. BLCA is one of the tumors considered suitable for immunotherapy because of the large proportion of immune cells in TME. Epithelial to mesenchymal transition (EMT) is closely related to tumor immunity through its crosstalk with immune cells. A recent study validated that EMT-related genes were mainly expressed by stromal cells and could influence immunotherapy responsiveness. Stromal EMT-related gene signature was also demonstrated to affect the prognosis of multiple tumors, including BLCA. To further explore the prognostic roles of stromal components, we performed a comprehensive analysis of LncRNAs closely associated with stromal EMT-related genes in the TCGA BLCA cohort. We identified a signature including five stromal EMT gene-related LncRNAs that showed significant prognostic value for BLCA patients. By the CIBERSORT and MCP-COUNTER algorithm, we found the signature was markedly correlated with infiltrated immune cells and stromal components of the tumor microenvironment, which may further influence patient’s responsiveness to immune checkpoint blockade therapy. Through immunohistochemical analysis, we confirmed the correlation of the signature with macrophages M2 and CAFs. Meanwhile, key genes related to these LncRNAs, including VIM, MMP2, were also differentially expressed in the stromal components concerning the signature. Our research confirmed the prognostic and immune-associated role of stromal EMT-related LncRNAs. Meantime, we further confirmed that EMT-related genes were mainly expressed in stromal components. Targeting these LncRNAs as well as their related stromal EMT genes may provide potential therapeutic targets for BLCA immunotherapy and precision medicine.
Oncogenic B-Myb Is Associated With Deregulation of the DREAM-Mediated Cell Cycle Gene Expression Program in High Grade Serous Ovarian Carcinoma Clinical Tumor Samples
Authors: Iness Audra N. , Rubinsak Lisa , Meas Steven J. , Chaoul Jessica , Sayeed Sadia , Pillappa Raghavendra , Temkin Sarah M. , Dozmorov Mikhail G. , Litovchick Larisa
Published: March 2021

Cell cycle control drives cancer progression and treatment response in high grade serous ovarian carcinoma (HGSOC). MYBL2 (encoding B-Myb), an oncogene with prognostic significance in several cancers, is highly expressed in most HGSOC cases; however, the clinical significance of B-Myb in this disease has not been well-characterized. B-Myb is associated with cell proliferation through formation of the MMB (Myb and MuvB core) protein complex required for transcription of mitotic genes. High B-Myb expression disrupts the formation of another transcriptional cell cycle regulatory complex involving the MuvB core, DREAM (DP, RB-like, E2F, and MuvB), in human cell lines. DREAM coordinates cell cycle dependent gene expression by repressing over 800 cell cycle genes in G0/G1. Here, we take a bioinformatics approach to further evaluate the effect of B-Myb expression on DREAM target genes in HGSOC and validate our cellular model with clinical specimens. We show that MYBL2 is highly expressed in HGSOC and correlates with expression of DREAM and MMB target genes in both The Cancer Genome Atlas (TCGA) as well as independent analyses of HGSOC primary tumors (N = 52). High B-Myb expression was also associated with poor overall survival in the TCGA cohort and analysis by a DREAM target gene expression signature yielded a negative impact on survival. Together, our data support the conclusion that high expression of MYBL2 is associated with deregulation of DREAM/MMB-mediated cell cycle gene expression programs in HGSOC and may serve as a prognostic factor independent of its cell cycle role. This provides rationale for further, larger scale studies aimed to determine the clinical predictive value of the B-Myb gene expression signature for treatment response as well as patient outcomes.
DNA Methylation of TLR4, VEGFA, and DEFA5 Is Associated With Necrotizing Enterocolitis in Preterm Infants
Authors: Klerk Daphne H. , Plösch Torsten , Verkaik-Schakel Rikst Nynke , Hulscher Jan B. F. , Kooi Elisabeth M. W. , Bos Arend F.
Published: March 2021

Background: Epigenetic changes, such as DNA methylation, may contribute to an increased susceptibility for developing necrotizing enterocolitis (NEC) in preterm infants. We assessed DNA methylation in five NEC-associated genes, selected from literature: EPO, VEGFA, ENOS, DEFA5, and TLR4 in infants with NEC and controls.

Methods: Observational cohort study including 24 preterm infants who developed NEC (≥Bell Stage IIA) and 45 matched controls. DNA was isolated from stool samples and methylation measured using pyrosequencing. We investigated differences in methylation prior to NEC compared with controls. Next, in NEC infants, we investigated methylation patterns long before, a short time before NEC onset, and after NEC.

Results: Prior to NEC, only TLR4 CpG 2 methylation was increased in NEC infants (median = 75.4%, IQR = 71.3–83.8%) versus controls (median = 69.0%, IQR = 64.5–77.4%, p = 0.025). In NEC infants, VEGFA CpG 3 methylation was 0.8% long before NEC, increasing to 1.8% a short time before NEC and 2.0% after NEC (p = 0.011; p = 0.021, respectively). A similar pattern was found in DEFA5 CpG 1, which increased from 75.4 to 81.4% and remained 85.3% (p = 0.027; p = 0.019, respectively). These changes were not present for EPO, ENOS, and TLR4.

Conclusion: Epigenetic changes of TLR4, VEGFA, and DEFA5 are present in NEC infants and can differ in relation to the time of NEC onset. Differences in DNA methylation of TLR4, VEGFA, and DEFA5 may influence gene expression and increase the risk for developing NEC. This study also demonstrates the use of human DNA extraction from stool samples as a novel non-invasive method for exploring the bowel of preterm infants and which can also be used for necrotizing enterocolitis patients.
The Effects of Bilirubin and Lumirubin on Metabolic and Oxidative Stress Markers
Authors: Dvořák Aleš , Pospíšilová Kateřina , Žížalová Kateřina , Capková Nikola , Muchová Lucie , Vecka Marek , Vrzáčková Nikola , Křížová Jana , Zelenka Jaroslav , Vítek Libor
Published: March 2021

For severe unconjugated hyperbilirubinemia the gold standard treatment is phototherapy with blue-green light, producing more polar photo-oxidation products, believed to be non-toxic. The aim of the present study was to compare the effects of bilirubin (BR) and lumirubin (LR), the major BR photo-oxidation product, on metabolic and oxidative stress markers. The biological activities of these pigments were investigated on several human and murine cell lines, with the focus on mitochondrial respiration, substrate metabolism, reactive oxygen species production, and the overall effects on cell viability. Compared to BR, LR was found to be much less toxic, while still maintaining a similar antioxidant capacity in the serum as well as suppressing activity leading to mitochondrial superoxide production. Nevertheless, due to its lower lipophilicity, LR was less efficient in preventing lipoperoxidation. The cytotoxicity of BR was affected by the cellular glycolytic reserve, most compromised in human hepatoblastoma HepG2 cells. The observed effects were correlated with changes in the production of tricarboxylic acid cycle metabolites. Both BR and LR modulated expression of PPARα downstream effectors involved in lipid and glucose metabolism. Proinflammatory effects of BR, evidenced by increased expression of TNFα upon exposure to bacterial lipopolysaccharide, were observed in murine macrophage-like RAW 264.7 cells. Collectively, these data point to the biological effects of BR and its photo-oxidation products, which might have clinical relevance in phototherapy-treated hyperbilirubinemic neonates and adult patients.
What Matters Most to Lung Cancer Patients? A Qualitative Study in Italy and Belgium to Investigate Patient Preferences
Authors: Petrocchi Serena , Janssens Rosanne , Oliveri Serena , Arnou Reinhard , Durosini Ilaria , Guiddi Paolo , Louis Evelyne , Vandevelde Marie , Nackaerts Kristiaan , Smith Meredith Y. , Galli Giulia , de Marinis Filippo , Gianoncelli Letizia , Pravettoni Gabriella , Huys Isabelle
Published: March 2021

Background: The potential value of patient preference studies has been recognized in clinical individual treatment decision-making between clinicians and patients, as well as in upstream drug decision-making. Drug developers, regulators, reimbursement and Health Technology Assessment (HTA) bodies are exploring how the use of patient preference studies could inform drug development, regulatory benefit risk-assessment and reimbursement decisions respectively. Understanding patient preferences may be especially valuable in decisions regarding Non-Small Cell Lung Cancer (NSCLC) treatment options, where a variety of treatment options with different characteristics raise uncertainty about which features are most important to NSCLC patients. As part of the Innovative Medicines Initiative PREFER project, this qualitative study aimed to identify patient-relevant lung cancer treatment characteristics.

Methods: This study consisted of a scoping literature review and four focus group discussions, 2 in Italy and 2 in Belgium, with a total of 24 NSCLC patients (Stages III-IV). The focus group discussions sought to identify which treatment characteristics patients find most relevant. The discussions were analyzed thematically using a thematic inductive analysis.

Results: Patients highlighted themes reflecting: 1) positive effects or expected gains from treatment such as greater life expectancy and maintenance of daily functioning, 2) negative effects or adverse events related to therapy that negatively impact patients’ daily functioning such as fatigue and 3) uncertainty regarding the duration and type of treatment effects. These overarching themes were consistent among patients from Belgium and Italy, suggesting that treatment aspects related to efficacy and safety as well as the psychological impact of lung cancer treatment are common areas of concern for patients, regardless of cultural background or country.

Discussion: Our findings illustrate the value of using qualitative methods with patients to identify preferred treatment characteristics for advanced lung cancer. These could inform a subsequent quantitative preference survey that assesses patient trade-offs regarding treatment options.
Meiocyte Isolation by INTACT and Meiotic Transcriptome Analysis in Arabidopsis
Authors: Barra Lucia , Termolino Pasquale , Aiese Cigliano Riccardo , Cremona Gaetana , Paparo Rosa , Lanzillo Carmine , Consiglio Maria Federica , Conicella Clara
Published: March 2021

Isolation of nuclei tagged in specific cell types (INTACT) is a method developed to isolate cell-type-specific nuclei that are tagged through in vivo biotin labeling of a nuclear targeting fusion (NTF) protein. In our work, INTACT was used to capture nuclei of meiocytes and to generate a meiotic transcriptome in Arabidopsis. Using the promoter of AtDMC1 recombinase to label meiotic nuclei, we generated transgenic plants carrying AtDMC1:NTF along with biotin ligase enzyme (BirA) under the constitutive ACTIN2 (ACT2) promoter. AtDMC1-driven expression of biotin-labeled NTF allowed us to collect nuclei of meiocytes by streptavidin-coated magnetic beads. The nuclear meiotic transcriptome was obtained by RNA-seq using low-quantity input RNA. Transcripts grouped into different categories according to their expression levels were investigated by gene ontology enrichment analysis (GOEA). The most enriched GO term “DNA demethylation” in mid/high-expression classes suggests that this biological process is particularly relevant to meiosis onset. The majority of genes with established roles in meiosis were distributed in the classes of mid/high and high expression. Meiotic transcriptome was compared with public available transcriptomes from other tissues in Arabidopsis. Bioinformatics analysis by expression network identified a core of more than 1,500 genes related to meiosis landmarks.
Personal Value Preferences, Threat-Benefit Appraisal of Immigrants and Levels of Social Contact: Looking Through the Lens of the Stereotype Content Model
Authors: Walsh Sophie D. , Tartakovsky Eugene
Published: March 2021

The study examines a model proposing relationships between personal values, positive (i.e., benefits) and negative (i.e., threats) appraisal of immigrants, and social contact. Based on a values-attitudes-behavior paradigm, the study extends previous work on personal values and attitudes to immigrants by examining not only negative but also positive appraisal and their connection with social contact with immigrants. Using a representative sample of 1,600 adults in the majority population in Israel, results showed that higher preference for anxiety-avoidance values (self-enhancement and conservation) was related to higher levels of perceived threat and lower levels of benefit, while higher preference for anxiety-free values (self-transcendence and openness to change) was related to higher levels of perceived benefits and lower levels of threat. Greater opportunities for contact and perceived benefits and lower levels of threats were related to more social contact. The model showed good fit across the total sample, and across four diverse immigrant groups in Israel (diaspora immigrants from the Former Soviet Union, Ethiopia and Western countries, and asylum seekers). In line with a Stereotype Content Model, which suggests that group-specific stereotypes are related to social structural characteristics of the group, associations between variables differed by group. Results strengthen a theoretical conceptualization that posits an indirect relationship between personal value preferences and behavior through group appraisal. They highlight the importance of comprehensive conceptualizations including both positive and negative appraisal of immigrants, which take into account the way different groups may be appraised by the majority population.
Narrative Coherence of Turning Point Memories: Associations With Psychological Well-Being, Identity Functioning, and Personality Disorder Symptoms
Authors: Vanderveren Elien , Bogaerts Annabel , Claes Laurence , Luyckx Koen , Hermans Dirk
Published: March 2021

Individuals develop a narrative identity through constructing and internalizing an evolving life story composed of significant autobiographical memories. The ability to narrate these memories in a coherent manner has been related to well-being, identity functioning, and personality pathology. Previous studies have particularly focused on coherence of life story narratives, overlooking coherence of single event memories that make up the life story. The present study addressed this gap by examining associations between narrative coherence of single turning point memories and psychological well-being, identity functioning, and personality disorder (PD) symptoms among 333 Belgian emerging adults (72.1% female;Mage= 22.56,SD= 3.13, age range = 18–30). In addition, the present study tested whether narrative coherence could predict unique variance in PD symptoms above and beyond identity and interpersonal functioning, both considered key components of personality pathology. The findings showed that narrative coherence was not significantly related to psychological well-being, but yielded significant negative associations with disturbed identity functioning and antisocial PD symptoms. Furthermore, narrative coherence predicted unique variance in antisocial PD symptoms above and beyond identity functioning, but did not predict unique variance in borderline and antisocial PD symptoms above and beyond both identity and interpersonal functioning. Collectively, these findings suggest that narrative incoherence within single event memories might be characteristic for disturbed identity functioning and antisocial personality pathology.
Effectiveness of a Family Support Intervention on Caregiving Burden in Family of Elderly Patients With Cognitive Decline After the COVID-19 Lockdown
Authors: Cravello Luca , Martini Eleonora , Viti Niccolò , Campanello Cristina , Assogna Francesca , Perotta Daniele
Published: March 2021

Background: The coronavirus disease 2019 (COVID-19) pandemic had a great impact on patients with cognitive decline or dementia. The lockdown period may exacerbate behavioral disorders and worsen distress of caregivers. The aim of this study is to evaluate the effectiveness of a family support intervention on the negative effects that the COVID-19 lockdown may have on patients and related caregivers.

Methods: We recruited patients whose related caregivers had attended a family support course before the COVID-19 lockdown. The course was for family members of patients with cognitive decline or dementia and consisted in eight meetings during which the participants received information about the disease, the management of neuropsychiatric symptoms, and community resources and services available for patients with dementia. Data on cognitive decline, neuropsychiatric symptoms, and functional status had been collected before the course with the Mini-Mental State Examination (MMSE), the Neuropsychiatric Inventory (NPI), and the Instrumental (IADL) and Basic (BADL) Activities of Daily Living scales, respectively. The caregiving burden had been evaluated at the end of the course by means of the Zarit Burden Interview (ZBI). After the COVID-19 lockdown, a phone interview was made to compare neuropsychiatric symptoms, functional status, and caregiver's burden with the previous evaluation.

Results: There were no significant changes before and after the COVID-19 lockdown in the mean NPI score. The IADL, BADL, and ZBI scores were significantly lower after lockdown than before. The BADL scores were inversely associated with ZBI scores. Thus, despite a worsening of patients' functional status, the caregivers' burden decreased significantly probably due to the positive effect of the family support intervention.

Conclusions: Our study demonstrated that a complete family support intervention for caregivers of patients with cognitive decline or dementia can reduce the burden of care even in a particular negative period, such as the COVID-19 lockdown.
Reduced Inter-hemispheric Resting State Functional Connectivity and Its Association With Social Deficits in Autism
Authors: Yao Shuxia , Becker Benjamin , Kendrick Keith M.
Published: March 2021

Autism spectrum disorder (ASD) is an early onset developmental disorder which persists throughout life and is increasing in prevalence over the last few decades. Given its early onset and variable cognitive and emotional functional impairments, it is generally challenging to assess ASD individuals using task-based behavioral and functional MRI paradigms. Consequently, resting state functional MRI (rs-fMRI) has become a key approach for examining ASD-associated neural alterations and revealed functional alterations in large-scale brain networks relative to typically developing (TD) individuals, particularly those involved in social-cognitive and affective processes. Recent progress suggests that alterations in inter-hemispheric resting state functional connectivity (rsFC) between regions in the 2 brain hemispheres, particularly homotopic ones, may be of great importance. Here we have reviewed neuroimaging studies examining inter-hemispheric rsFC abnormities in ASD and its associations with symptom severity. As an index of inter-hemispheric functional connectivity, we have additionally reviewed previous studies on corpus callosum (CC) volumetric and fiber changes in ASD. There are converging findings on reduced inter-hemispheric (including homotopic) rsFC in large-scale brain networks particularly in posterior hubs of the default mode network, reduced volumes in the anterior and posterior CC, and on decreased FA and increased MD or RD across CC subregions. Associations between the strength of inter-hemispheric rsFC and social impairments in ASD together with their classification performance in distinguishing ASD subjects from TD controls across ages suggest that the strength of inter-hemispheric rsFC may be a more promising biomarker for assisting in ASD diagnosis than abnormalities in either brain wide rsFC or brain structure.
A Universal Approach to Molecular Identification of Rumen Fluke Species Across Hosts, Continents, and Sample Types
Authors: Mitchell Gillian , Zadoks Ruth N. , Skuce Philip J.
Published: March 2021

Rumen fluke are parasitic trematodes that affect domestic and wild ruminants across a wide range of countries and habitats. There are 6 major genera of rumen fluke and over 70 recognized species. Accurate species identification is important to investigate the epidemiology, pathophysiology and economic impact of rumen fluke species but paramphistomes are morphologically plastic, which has resulted in numerous instances of misclassification. Here, we present a universal approach to molecular identification of rumen fluke species, including different life-cycle stages (eggs, juvenile and mature fluke) and sample preservation methods (fresh, ethanol- or formalin-fixed, and paraffin wax-embedded). Among 387 specimens from 173 animals belonging to 10 host species and originating from 14 countries on 5 continents, 10 rumen fluke species were identified based on ITS-2 intergenic spacer sequencing, including members of the genera Calicophoron, Cotylophoron, Fischeroedius, Gastrothylax, Orthocoelium, and Paramphistomum. Pairwise comparison of ITS-2 sequences from this study and GenBank showed >98.5% homology for 80% of intra-species comparisons and <98.5% homology for 97% of inter-species comparisons, suggesting that some sequence data may have been entered into public repositories with incorrect species attribution based on morphological analysis. We propose that ITS-2 sequencing could be used as a universal tool for rumen fluke identification across host and parasite species from diverse technical and geographical origins and form the basis of an international reference database for accurate species identification.
Assessment of Performance and Some Welfare Indicators of Cows in Vietnamese Smallholder Dairy Farms
Authors: Bang Nguyen N. , Chanh Nguyen V. , Trach Nguyen X. , Khang Duong N. , Hayes Ben J. , Gaughan John B. , Lyons Russell E. , Hai Nguyen T. , McNeill David M.
Published: March 2021

Smallholder dairy farms (SDFs) are distributed widely across lowland and highland regions in Vietnam, but data on the productivity and welfare status of these cows remains limited. This cross-sectional study was conducted to describe and compare the productivity and welfare status of SDF cows across contrasting regions. It was conducted in autumn 2017 on 32 SDFs randomly selected from four typical but contrasting dairy regions (eight SDFs per region); a south lowland, a south highland, a north lowland, and a north highland region. Each farm was visited over a 24-h period (an afternoon followed by a morning milking and adjacent husbandry activities) to collect data of individual lactating cows (n = 345) and dry cows (n = 123), which included: milk yield and concentrations, body weight (BW), body condition score (BCS, 5-point scale, 5 = very fat), inseminations per conception, and level of heat stress experienced (panting score, 4.5-point scale, 0 = no stress). The high level of heat stress (96% of lactating cows were moderate to highly heat-stressed in the afternoon), low energy corrected milk yield (15.7 kg/cow/d), low percentage of lactating cows (37.3% herd), low BW (498 and 521 kg in lactating and dry cows, respectively), and low BCS of lactating cows (2.8) were the most important productivity and welfare concerns determined and these were most serious in the south lowland. By contrast, cows in the north lowland, a relatively hot but new dairying region, performed similarly to those in the south highland; a region historically considered to be one of the most suitable for dairy cows in Vietnam due to its cool environment. This indicates the potential to mitigate heat stress through new husbandry strategies. Cows in the north highland had the highest BW (535 and 569 kg in lactating and dry cows, respectively) and the highest energy corrected milk yield (19.2 kg/cow/d). Cows in all regions were heat-stressed during the daytime, although less so in the highlands compared to the lowlands. Opportunities for research into improving the productivity and welfare of Vietnamese SDF cows are discussed.
Melatonin for the Management of Preeclampsia: A Review
Authors: Langston-Cox Annie , Marshall Sarah A. , Lu Daisy , Palmer Kirsten R. , Wallace Euan M.
Published: March 2021

Preeclampsia is a disease specific to pregnancy characterised by new-onset hypertension with maternal organ dysfunction and/or fetal growth restriction. It remains a major cause of maternal and perinatal morbidity and mortality. For sixty years, antihypertensives have been the mainstay of treating preeclampsia and only recently have insights into the pathogenesis of the disease opened new avenues for novel therapies. Melatonin is one such option, an endogenous and safe antioxidant, that may improve the maternal condition in preeclampsia while protecting the fetus from a hostile intrauterine environment. Here we review the evidence for melatonin as a possible adjuvant therapy for preeclampsia, including in vitro evidence supporting a role for melatonin in protecting the human placenta, preclinical models, vascular studies, and clinical studies in hypertension and pregnancy.