bluuebunny/crossref_metadata_2025 huggingface dataset:
Prognostic Risk Model of Immune-Related Genes in Colorectal Cancer
Authors: Qian Yucheng , Wei Jingsun , Lu Wei , Sun Fangfang , Hwang Maxwell , Jiang Kai , Fu Dongliang , Zhou Xinyi , Kong Xiangxing , Zhu Yingshuang , Xiao Qian , Hu Yeting , Ding Kefeng
Published: March 2021

Purpose

We focused on immune-related genes (IRGs) derived from transcriptomic studies, which had the potential to stratify patients’ prognosis and to establish a risk assessment model in colorectal cancer.

This article examined our understanding of the molecular pathways associated with intratumoral immune response, which represented a critical step for the implementation of stratification strategies toward the development of personalized immunotherapy of colorectal cancer. More and more evidence shows that IRGs play an important role in tumors. We have used data analysis to screen and identify immune-related molecular biomarkers of colon cancer. We selected 18 immune-related prognostic genes and established models to assess prognostic risks of patients, which can provide recommendations for clinical treatment and follow-up. Colorectal cancer (CRC) is a leading cause of cancer-related death in human. Several studies have investigated whether IRGs and tumor immune microenvironment (TIME) could be indicators of CRC prognoses. This study aimed to develop an improved prognostic signature for CRC based on IRGs to predict overall survival (OS) and provide new therapeutic targets for CRC treatment. Based on the screened IRGs, the Cox regression model was used to build a prediction model based on 18-IRG signature. Cox regression analysis revealed that the 18-IRG signature was an independent prognostic factor for OS in CRC patients. Then, we used the TIMER online database to explore the relationship between the risk scoring model and the infiltration of immune cells, and the results showed that the risk model can reflect the state of TIME to a certain extent. In short, an 18-IRG prognostic signature for predicting CRC patients’ survival was firmly established.
Upregulated IL-6 Indicates a Poor COVID-19 Prognosis: A Call for Tocilizumab and Convalescent Plasma Treatment
Authors: Wu Jian , Shen Jiawei , Han Ying , Qiao Qinghua , Dai Wei , He Bangshun , Pang Rongrong , Zhao Jun , Luo Tao , Guo Yanju , Yang Yang , Wu Qiuyue , Jiang Weijun , Zhang Jing , Zhang Mingchao , Li Na , Li Weiwei , Xia Xinyi
Published: March 2021

A comprehensive understanding of the dynamic changes in interleukin-6 (IL-6) levels is essential for monitoring and treating patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2). By analyzing the correlations between IL-6 levels and health conditions, underlying diseases, several key laboratory detection indices, and the prognosis of 1,473 patients with the coronavirus disease 2019 (COVID-19), the role of IL-6 during SARS-CoV-2 infection was demonstrated. Our results indicated that IL-6 levels were closely related to age, sex, body temperature, oxygen saturation (SpO2) of blood, and underlying diseases. As a stable indicator, the changes in IL-6 levels could indicate the inflammatory conditions during a viral infection. Two specific treatments, namely, tocilizumab and convalescent plasma therapy (CPT), decreased the level of IL-6 and relieved inflammation. CPT has an important role in the therapy for patients with critical COVID-19. We also found that patients with IL-6 levels, which were 30-fold higher than the normal level, had a poor prognosis compared to patients with lower levels of IL-6.
Blogging as a Tool for Real-Time Learning in Medical Microbiology
Authors: Lloyd Charmaine
Published: March 2021

Blogging is a widely used social medium for storing and sharing information online. Being an attractive online interface, some studies show that education blogging or edublogging might promote more engaged learning. An apathy to contemporary issues related to one’s area of study can result in a less knowledgeable student who is less ready for the job industry. To bridge the gap between classroom learning and awareness of emerging issues pertaining to the field of study and potential employment – blogging of ongoing events in a select microbiological field was proposed as a graded semester-long activity called “Disease Tracking.” The exercise involved instructing students to choose one infectious disease topic, for which traditional and non-traditional scientific information could be sourced with high frequency over the preceding months. Students were to document new information on the topic as it became available over the term, from reliable information resources. At the end of the term, students presented their work in a “Blog show-off” presentation session. Blog-based learning was found to be an engaging tool that satisfied all criteria under Bloom’s taxonomy. Students developed a continued intrigue for the chosen topic and appreciated the diverse fields in which fundamentals of infectious diseases learned in class, could be applied within and outside academia. Students also valued this experience and feedback showed that the freedom to choose their own topic (77%), opportunity to learn more from other students’ blogs (77%), less stress as they were not competing on identical topics (73%), a “fun way” to learn (68%), and an opportunity to understand the importance of staying abreast with scientific news (64%) stood out as the chief positive points of the exercise to the students. In view of these benefits, blogs can be used for an immersive, broad learning experience in Microbiology and other fields in which there is likely to be a frequency of new information online.
Human Placental Trophoblasts Are Resistant to Trypanosoma cruzi Infection in a 3D-Culture Model of the Maternal-Fetal Interface
Authors: Silberstein Erica , Kim Kwang Sik , Acosta David , Debrabant Alain
Published: March 2021

Trypanosoma cruzi (T. cruzi), the etiological agent of Chagas Disease (CD), is transmitted to humans by infected kissing bugs, blood transfusion, organ transplantation, and from mother-to-child. Congenital transmission is now considered an important route of CD spread in non-endemic countries where no routine testing of pregnant women for the disease is implemented. The main cellular mechanisms that lead to fetal infection by T. cruzi, despite the presence of a placental barrier, remain unclear. Mother-to-child transmission most likely occurs when bloodstream trypomastigotes reach the placental intervillous space and interact with the large cellular surface provided by the syncytioptrophoblasts. These highly specialized cells not only function as a physical obstacle between mother and fetus, but also modulate immune responses against pathogen infections. To overcome the limitations associated with the use of human fetal tissues, we employed a three-dimensional (3D) cell culture model to recreate the human placenta environment. In this system, the trophoblast-derived JEG-3 cell line is co-cultured with human brain microvascular endothelial cells attached to microcarrier beads in a rotating bioreactor. Here, we report that 3D culture of JEG-3/HBMEC spheroids promote JEG-3 cells differentiation revealed by the formation of syncytia and production of β human chorionic gonadotropin and human placental lactogen (hPL). Under these growth conditions, we demonstrate that 3D-grown JEG-3 cells have reduced susceptibility to T. cruzi infection compared to JEG-3 cells grown in conventional tissue culture flasks. We also show that 3D-cultured JEG-3 cells release paracrine factors in the supernatant that prevent T. cruzi infection of non-trophoblastic cell lines. Our in vitro model of T. cruzi vertical transmission may help better understand the molecular processes by which parasites bypass the human placental barrier and could be exploited to evaluate therapeutics to reduce congenital CD.
Visual Modulation of Human Responses to Support Surface Translation
Authors: Akçay Mustafa Emre , Lippi Vittorio , Mergner Thomas
Published: March 2021

Vision is known to improve human postural responses to external perturbations. This study investigates the role of vision for the responses to continuous pseudorandom support surface translations in the body sagittal plane in three visual conditions: with the eyes closed (EC), in stroboscopic illumination (EO/SI; only visual position information) and with eyes open in continuous illumination (EO/CI; position and velocity information) with the room as static visual scene (or the interior of a moving cabin, in some of the trials). In the frequency spectrum of the translation stimulus we distinguished on the basis of the response patterns between a low-frequency, mid-frequency, and high-frequency range (LFR: 0.0165-0.14 Hz; MFR: 0.15–0.57 Hz; HFR: 0.58–2.46 Hz). With EC, subjects’ mean sway response gain was very low in the LFR. On average it increased with EO/SI (although not to a significant degree p = 0.078) and more so with EO/CI (p < 10−6). In contrast, the average gain in the MFR decreased from EC to EO/SI (although not to a significant degree, p = 0.548) and further to EO/CI (p = 0.0002). In the HFR, all three visual conditions produced, similarly, high gain levels. A single inverted pendulum (SIP) model controlling center of mass (COM) balancing about the ankle joints formally described the EC response as being strongly shaped by a resonance phenomenon arising primarily from the control’s proprioceptive feedback loop. The effect of adding visual information in these simulations lies in a reduction of the resonance, similar as in the experiments. Extending the model to a double inverted pendulum (DIP) suggested in addition a biomechanical damping effective from trunk sway in the hip joints on the resonance.
Digenic Variants in the TTN and TRAPPC11 Genes Co-segregating With a Limb-Girdle Muscular Dystrophy in a Han Chinese Family
Authors: Chen Qian , Zheng Wen , Xu Hongbo , Yang Yan , Song Zhi , Yuan Lamei , Deng Hao
Published: March 2021

Limb-girdle muscular dystrophies (LGMD) are hereditary genetic disorders characterized by progressive muscle impairment which predominantly include proximal muscle weaknesses in the pelvic and shoulder girdles. This article describes an attempt to identify genetic cause(s) for a LGMD pedigree via a combination of whole exome sequencing and Sanger sequencing. Digenic variants, the titin gene (TTN) c.19481T>G (p.Leu6494Arg) and the trafficking protein particle complex 11 gene (TRAPPC11) c.3092C>G (p.Pro1031Arg), co-segregated with the disease phenotype in the family, suggesting their possible pathogenicity.
Paraventricular Nucleus Infusion of Oligomeric Proantho Cyanidins Improves Renovascular Hypertension
Authors: Yu Xiao-Jing , Xin Guo-Rui , Liu Kai-Li , Liu Xiao-Jing , Fu Li-Yan , Qi Jie , Kang Kai B. , Meng Ting-Ting , Yi Qiu-Yue , Li Ying , Sun Yao-Jun , Kang Yu-Ming
Published: March 2021

Oxidative stress plays an important role in the pathogenesis of hypertension. Oligomeric proantho cyanidins (OPC) is the main polyphenol presents in grape seed and is known for its potent antioxidant and anti-inflammatory properties. In the present study, we hypothesize that OPC can attenuate oxidative stress in the paraventricular nucleus of hypothalamus (PVN), ameliorate neurotransmitter imbalance, decrease the blood pressure and sympathetic activity in renovascular hypertensive rats. After induction of renovascular hypertension by the two-kidney one-clip (2K-1C) method, male Sprague-Dawley rats received chronic bilateral PVN infusion of OPC (20 μg/h) or vehicle via osmotic minipump for 4 weeks. We found that hypertension induced by 2K-1C was associated with the production of reactive oxygen species (ROS) in the PVN. Infusion of OPC in the PVN significantly reduced the systolic blood pressure and norepinephrine in plasma of 2K-1C rats. In addition, PVN infusion of OPC decreased the level of ROS and the expression of stress-related nicotinamide adenine dinucleotide phosphate (NADPH) oxidases subunit NOX4, increased the levels of nuclear factor E2-related factor 2 (Nrf2) and antioxidant enzyme, balanced the content of cytokines, increased expression of glutamic acid decarboxylase and decreased the expression of tyrosine hydroxylase in the PVN of 2K-1C rats. Our findings provided strong evidence that PVN infusion of OPC inhibited the progression of renovascular hypertension through its potent anti-oxidative and anti-inflammatory function in the PVN.
Survival Significance of Number of Positive Lymph Nodes in Oral Squamous Cell Carcinoma Stratified by p16
Authors: Li Peng , Fang Qigen , Yang Yanjie , Chen Defeng , Du Wei , Liu Fei , Luo Ruihua
Published: March 2021

Objectives: To analyze the significance of the number of positive lymph nodes in oral squamous cell carcinoma (SCC) stratified by p16.

Methods: A total of 674 patients were retrospectively enrolled and divided into 4 groups based on their number of positive lymph nodes (0 vs. 1–2 vs. 3–4 vs. ≥5). The Kaplan-Meier method was used to calculate the disease-free survival (DFS) and disease-specific survival (DSS) rates. Cox model was used to evaluate the independent risk factor.

Results: p16 showed positivity in 85 patients with a rate of 12.6%. In patients with p16 negativity, the 5-year DFS rates were 52%, 39%, and 21% in patients with 0, 1–2, and 3–4 positive lymph nodes, respectively, in patients with ≥5 positive lymph nodes, all patients developed recurrence within 2 years after operation, the difference was significant; the 5-year DSS rates were 60, 38, and 18% in patients with 0, 1–2, and 3–4 positive lymph nodes, respectively, in patients with ≥5 positive lymph nodes, all patients died within 4-years after operation. The difference was significant. In p16 positivity patients, the 3-year DFS rates were 41% and 17% in patients with 0–2 and ≥3 positive lymph nodes, respectively, the difference was significant; the 3-year DSS rates were 84 and 46% in patients with 0–2 and ≥3 positive lymph nodes, the difference was significant.

Conclusions: The number of positive lymph nodes is significantly associated with the survival in oral SCC, its survival effect is not affected by p16 status.
Very-Low-Dose Levodopa Therapy for Pediatric Neurological Disorders: A Preliminary Questionnaire in Japan
Authors: Hoshino Kyoko , Hayashi Masaharu , Ishizaki Asayo , Kimura Kazue , Kubota Masaya , Nezu Atsuo , Yasuhara Akihiro
Published: March 2021

Introduction: Post-synaptic dopamine receptor supersensitivity (DARSS) has been extensively researched by Dr. Masaya Segawa, who has investigated the efficacy of very-low-dose levodopa therapy (VLDT; 0.5–1 mg/kg/day). Considerable Japanese research supports the possibility that VLDT could be used to treat pediatric neurological disorders. We conducted an on-line survey in 2014 to collect real-world data on the use of VLDT to treat DARSS.

Methods: A two-step survey, including a screening test and questionnaire, was posted on a private internet site that could be accessed via the VLDT Research Group home page, and 1,165 pediatric neurologists across Japan were invited to complete it.

Results: A total of 25 respondents reported prescribing VLDT; 19 used VLDT to treat autism spectrum disorder, 14 for tics, 12 for speech delay, 9 for Rett syndrome, 7 for attention-deficit/hyperactivity disorder, intellectual disability, and 6 for sleep problems. Twelve respondents reported prescribing a dose of 0.5 mg/kg. Twenty-two reported that VLDT was effective for treating behavioral problems, and twenty reported a good efficacy for treating motor symptoms. Adverse events had a low incidence. Notably, respondents chose VLDT for its possible action in DARSS and for its safety. VLDT was commonly used for behavioral problems in patients younger than 5 years, and for motor symptoms in aged 5–9 years.

Conclusion: VLDT could safely treat behavioral and motor symptoms in pediatric neurological disorders. In contrast, dopamine antagonists are associated with potent efficacy, but with adverse effects such as sleepiness and obesity. Further surveys should be conducted with a broader participants.
Analysis of Antidepressant Activity of Huang-Lian Jie-Du Decoction Through Network Pharmacology and Metabolomics
Authors: Qu Shu-Yue , Li Xiao-Yue , Heng Xia , Qi Yi-Yu , Ge Ping-Yuan , Ni Sai-jia , Yao Zeng-Ying , Guo Rui , Yang Nian-Yun , Cao Yi , Zhang Qi-Chun , Zhu Hua-Xu
Published: March 2021

Depressive disorder is a common mental disorder characterized by depressed mood and loss of interest or pleasure. As the Herbal medicines are mainly used as complementary and alternative therapy for depression. This study aimed at exploring antidepressant activity of Huang-lian Jie-du Decoction (HLJDD), and evaluating active components and potential depression-associated targets. HLJDD was administered on chronic unpredictable mild stress-induced (CUMS) depressive mice. Behavior evaluation was performed through force swimming test (FST), novelty-suppressed feeding test (NSF), and open field test (OFT). Active components of HLJDD, potential targets, and metabolic pathways involved in depression were explored through systemic biology-based network pharmacology assay, molecular docking and metabonomics. FST assay showed that CUMS mice administered with HLJDD had significantly shorter immobility time compared with control mice. Further, HLJDD alleviated feeding latency of CUMS mice in NSFand increased moving distance and duration in OFT. In the following network pharmacology assay, thirty-eight active compounds in HLJDD were identified based on drug-like characteristics, and pharmacokinetics and pharmacodynamics profiles. Moreover, forty-eight molecular targets and ten biochemical pathways were uncovered through molecular docking and metabonomics. GRIN2B, DRD, PRKCA, HTR, MAOA, SLC6A4, GRIN2A, and CACNA1A are implicated in inhibition of depressive symptoms through modulating tryptophan metabolism, serotonergic and dopaminergic synaptic activities, cAMP signaling pathway, and calcium signaling pathway. Further network pharmacology-based analysis showed a correlation between HLJDD and tryptophan metabolism. A total of thirty-seven active compounds, seventy-six targets, and sixteen biochemical pathways were involved in tryptophan metabolism. These findings show that HLJDD acts on potential targets such as SLC6A4, HTR, INS, MAO, CAT, and FoxO, PI3K/Akt, calcium, HIF-1, and mTOR signaling pathways, and modulates serotoninergic and dopaminergic synaptic functions. In addition, metabonomics showed that tryptophan metabolism is the primary target for HLJDD in CUMS mice. The findings of the study show that HLJDD exhibited antidepressant effects. SLC6A4 and MAOA in tryptophan metabolism were modulated by berberine, baicalein, tetrahydroberberine, candicine and may be the main antidepressant targets for HLJDD.
Early Growth and Protein-Energy Metabolism in Chicken Lines Divergently Selected on Ultimate pH
Authors: Métayer-Coustard Sonia , Tesseraud Sophie , Praud Christophe , Royer David , Bordeau Thierry , Coudert Edouard , Cailleau-Audouin Estelle , Godet Estelle , Delaveau Joël , Le Bihan-Duval Elisabeth , Berri Cécile
Published: March 2021

In chickens, a divergent selection on the Pectoralis major pHu allowed the creation of the pHu+ and pHu− lines, which represent a unique model for studying the biological control of carbohydrate storage in muscle. The present study aimed to describe the early mechanisms involved in the establishment of pHu+ and pHu− phenotypes. At hatching, pHu+ chicks were slightly heavier but exhibited lower plasma glucose and triglyceride and higher uric acid. After 5 days, pHu+ chicks exhibited higher breast meat yield compared to pHu− while their body weight was no different. At both ages, in vivo muscle glycogen content was lower in pHu+ than in pHu− muscles. The lower ability of pHu+ chicks to store carbohydrate in their muscle was associated with the increased expression of SLC2A1 and SLC2A3 genes coding glucose transporters 1 and 3, and of CS and LDHα coding key enzymes of oxidative and glycolytic pathways, respectively. Reduced muscle glycogen content at hatching of the pHu+ was concomitant with higher activation by phosphorylation of S6 kinase 1/ribosomal protein S6 pathway, known to activate protein synthesis in chicken muscle. In conclusion, differences observed in muscle at slaughter age in the pHu+ and pHu− lines are already present at hatching. They are associated with several changes related to both carbohydrate and protein metabolism, which are likely to affect their ability to use eggs or exogenous nutrients for muscle growth or energy storage.
Defeat, Entrapment, and Positive Future Thinking: Examining Key Theoretical Predictors of Suicidal Ideation Among Adolescents
Authors: Pollak Olivia H. , Guzmán Eleonora M. , Shin Ki Eun , Cha Christine B.
Published: March 2021

Adult-based suicide theories have determined much of what we know about suicidal ideation. Here, we investigate the extent to which elements of theIntegrated Motivational-Volitional(IMV) model generalize to adolescence, a period when rates of suicidal ideation increase dramatically. In a sample of community-based adolescents (n= 74), we tested whether defeat and entrapment related to suicidal ideation, and whether poor positive future thinking abilities exacerbated this association. Consistent with the IMV model, we found that defeat/entrapment was associated specifically with history of suicidal ideation, and not with history of suicide attempt. Defeat/entrapment was related to baseline suicidal ideation severity above and beyond depressive symptoms. While defeat/entrapment predicted future suicidal ideation controlling for history of ideation, it did not do so controlling for depressive symptoms. Counter to the IMV model, we initially found that the association between defeat/entrapment and suicidal ideation was strongest among adolescents withgreaterpositive future thinking abilities. This was driven by the tendency to imagine more positive future events, particularly those that are less realistic and achievable. These findings call for a more nuanced understanding of defeat/entrapment and positive future thinking among adolescents, particularly in how they interact to predict recurrent suicidal ideation.
Social Support, Attachment Closeness, and Self-Esteem Affect Depression in International Students in China
Authors: Li Yawen , Liang Fei , Xu Qiuyue , Gu Simeng , Wang Yansong , Li Yang , Zeng Zhi
Published: March 2021

With an increase in the number of international students in China, there has been a simultaneous increase in their emotional problems, such as depression, as well as the importance of their emotional well-being. This study aimed to investigate the influence of social support on depression and the mediation and moderation mechanisms of this relationship in international students. In total, 349 international students in China responded to a questionnaire survey comprising the Social Support Rating Scale, Self-rating Depression Scale, Adult Attachment Scale, and Self-Esteem Scale. The results showed that: (1) attachment closeness had a significant direct predictive effect on depression; (2) attachment closeness played a mediating role in the relationship between social support and depression; and (3) the direct effect of social support on depression and the mediating effect of attachment and closeness are regulated by self-esteem. Therefore, interventions aimed at improving the social support, attachment closeness, and self-esteem of international students in China can be effective in reducing their depressive symptoms.
“Argue With Me”: A Method for Developing Argument Skills
Authors: Iordanou Kalypso , Rapanta Chrysi
Published: March 2021

Philosophers, psychologists, and educators all acknowledge the need to support individuals to develop argument skills. Less clear ishowto do so. Here, we examine a particular program, the “Argue with Me” dialogue-based pedagogical approach, having this objective. Reviewing approximately 30 studies that have used the “Argue with Me” (AWM) method with students of different backgrounds and educational levels—primary, middle, high school, and university—across five different countries, we examine its strengths and limitations in terms of what develops and how this development occurs. Dense engagement in goal-based activities involving extended dialogic practice and reflection is shown to be effective in fostering argument skills and dispositions. Studies examining the mechanisms of such development identify the role ofmeta-levelunderstanding regarding the purpose of argument. This understanding is epistemological in nature and supports the development of dialogic skills at the strategic level. In addition to examining the AWM method as a means for supporting the development of argument skills, this review examines how empirical research employing the method in varying contexts provides insights into the nature of argument skills and their development, as well as the relations between argument skills and other skills or forms of understanding. For instance, we examine how studies employing the AWM method answer questions such as “How general or content-specific are argument skills?” or “How do dialogic argument and individual written or spoken argument connect as they develop?” We address these questions by examining evidence regarding the transfer of gains across topics, domains, and individual vs. dialogic modes of expression. Finally, the pedagogical implications of the “Argue with Me” approach are discussed, especially with regard to its potential both as a stand-alone method for developing argument skills and integrated into traditional literacy and social studies curricula.
Preliminary Investigation of Bovine Whole Blood Xenotransfusion as a Therapeutic Modality for the Treatment of Anemia in Goats
Authors: Smith Joe S. , Viall Austin K. , Breuer Ryan M. , Walton Rebecca A. , Plummer Paul J. , Griffith Ronald W. , Kreuder Amanda J.
Published: March 2021

Anemia requiring whole blood transfusion for appropriate treatment is a common clinical presentation of caprine patients to veterinary practitioners; however, identifying suitable blood donors in goat herds can be challenging. In other veterinary species, the practice of xenotransfusion, where blood from 1 species is transfused to another, is used in emergency settings. Due to their ability to donate large volumes of whole blood, cattle could be an ideal source for xenotransfusion of goats. In this study 2 healthy goats were transfused with bovine whole blood. The goats were then monitored for adverse effects and the presence of bovine erythrocyte post-xenotransfusion. Afterward, 15 caprine–bovine combinations were evaluated for compatibility via cross-matching. Both goats tolerated xenotransfusion, although transient reactions were observed. Of the 15 cross-match combinations, 11 of the major cross matches were compatible, and all minor cross matches were also compatible. While future work is necessary to refine this technique, xenotransfusion of goats with cattle blood may be a therapeutic modality for the treatment of caprine anemia.
Standard of Care and Promising New Agents for the Treatment of Mesenchymal Triple-Negative Breast Cancer
Authors: Mezi Silvia , Botticelli Andrea , Pomati Giulia , Cerbelli Bruna , Scagnoli Simone , Amirhassankhani Sasan , d’Amati Giulia , Marchetti Paolo
Published: March 2021

The pathologic definition of triple negative breast cancer (TNBC) relies on the absence of expression of estrogen, progesterone and HER2 receptors. However, this BC subgroup is distinguished by a wide biological, molecular and clinical heterogeneity. Among the intrinsic TNBC subtypes, the mesenchymal type is defined by the expression of genes involved in the epithelial to mesenchymal transition, stromal interaction and cell motility. Moreover, it shows a high expression of genes involved in proliferation and an immune-suppressive microenvironment. Several molecular alterations along different pathways activated during carcinogenesis and tumor progression have been outlined and could be involved in immune evasion mechanisms. Furthermore, reverting epithelial to mesenchymal transition process could lead to the overcoming of immune-resistance. This paper reviews the current knowledge regarding the mesenchymal TNBC subtype and its response to conventional therapeutic strategies, as well as to some promising molecular target agents and immunotherapy. The final goal is a tailored combination of cytotoxic drugs, target agents and immunotherapy in order to restore immunocompetence in mesenchymal breast cancer patients.
Use of Measurable Residual Disease to Evolve Transplant Policy in Acute Myeloid Leukemia: A 20-Year Monocentric Observation
Authors: Buccisano Francesco , Palmieri Raffaele , Piciocchi Alfonso , Maurillo Luca , Del Principe Maria Ilaria , Paterno Giovangiacinto , Soddu Stefano , Cerretti Raffaella , De Angelis Gottardo , Mariotti Benedetta , Irno Consalvo Maria Antonietta , Conti Consuelo , Fraboni Daniela , Divona Mariadomenica , Ottone Tiziana , Lavorgna Serena , Panetta Paola , Voso Maria Teresa , Arcese William , Venditti Adriano
Published: March 2021

Measurable residual disease (MRD) is increasingly employed as a biomarker of quality of complete remission (CR) in intensively treated acute myeloid leukemia (AML) patients. We evaluated if a MRD-driven transplant policy improved outcome as compared to a policy solely relying on a familiar donor availability. High-risk patients (adverse karyotype, FLT3-ITD) received allogeneic hematopoietic cell transplant (alloHCT) whereas for intermediate and low risk ones (CBF-AML and NPM1-mutated), alloHCT or autologous SCT was delivered depending on the post-consolidation measurable residual disease (MRD) status, as assessed by flow cytometry. For comparison, we analyzed a matched historical cohort of patients in whom alloHCT was delivered based on the sole availability of a matched sibling donor. Ten-years overall and disease-free survival were longer in the MRD-driven cohort as compared to the historical cohort (47.7% vs. 28.7%, p = 0.012 and 42.0% vs. 19.5%, p = 0.0003). The favorable impact of this MRD-driven strategy was evident for the intermediate-risk category, particularly for MRD positive patients. In the low-risk category, the significantly lower CIR of the MRD-driven cohort did not translate into a survival advantage. In conclusion, a MRD-driven transplant allocation may play a better role than the one based on the simple donor availability. This approach determines a superior outcome of intermediate-risk patients whereat in low-risk ones a careful evaluation is needed for transplant allocation.
From a Point Cloud to a Simulation Model—Bayesian Segmentation and Entropy Based Uncertainty Estimation for 3D Modelling
Authors: Petschnigg Christina , Spitzner Markus , Weitzendorf Lucas , Pilz Jürgen
Published: March 2021

The 3D modelling of indoor environments and the generation of process simulations play an important role in factory and assembly planning. In brownfield planning cases, existing data are often outdated and incomplete especially for older plants, which were mostly planned in 2D. Thus, current environment models cannot be generated directly on the basis of existing data and a holistic approach on how to build such a factory model in a highly automated fashion is mostly non-existent. Major steps in generating an environment model of a production plant include data collection, data pre-processing and object identification as well as pose estimation. In this work, we elaborate on a methodical modelling approach, which starts with the digitalization of large-scale indoor environments and ends with the generation of a static environment or simulation model. The object identification step is realized using a Bayesian neural network capable of point cloud segmentation. We elaborate on the impact of the uncertainty information estimated by a Bayesian segmentation framework on the accuracy of the generated environment model. The steps of data collection and point cloud segmentation as well as the resulting model accuracy are evaluated on a real-world data set collected at the assembly line of a large-scale automotive production plant. The Bayesian segmentation network clearly surpasses the performance of the frequentist baseline and allows us to considerably increase the accuracy of the model placement in a simulation scene.
A New Modeling Approach for Low-Carbon District Energy System Planning
Authors: Rezaei Abolfazl , Samadzadegan Bahador , Rasoulian Hadise , Ranjbar Saeed , Samareh Abolhassani Soroush , Sanei Azin , Eicker Ursula
Published: March 2021

Designing district-scale energy systems with renewable energy sources is still a challenge, as it involves modeling of multiple loads and many options to combine energy system components. In the current study, two different energy system scenarios for a district in Montreal/Canada are compared to choose the most cost-effective and energy-efficient energy system scenario for the studied area. In the first scenario, a decentral energy system comprised of ground-source heat pumps provides heating and cooling for each building, while, in the second scenario, a district heating and cooling system with a central heat pump is designed. Firstly, heating and cooling demand are calculated in a completely automated process using an Automatic Urban Building Energy Modeling System approach (AUBEM). Then, the Integrated Simulation Environment Language (INSEL) is used to prepare a model for the energy system. The proposed model provides heat pump capacity and the number of required heat pumps (HP), the number of photovoltaic (PV) panels, and AC electricity generation potential using PV. After designing the energy systems, the piping system, heat losses, and temperature distribution of the centralized scenario are calculated using a MATLAB code. Finally, two scenarios are assessed economically using the Levelized Cost of Energy (LCOE) method. The results show that the central scenario’s total HP electricity consumption is 17% lower than that of the decentral systems and requires less heat pump capacity than the decentral scenario. The LCOE of both scenarios varies from 0.04 to 0.07 CAD/kWh, which is cheaper than the electricity cost in Quebec (0.08 CAD/kWh). A comparison between both scenarios shows that the centralized energy system is cost-beneficial for all buildings and, after applying the discounts, the LCOE of this scenario decreases to 0.04 CAD/kWh.
Development of Flexible Triboelectric Generators Based on Patterned Conductive Textile and PDMS Layers
Authors: Jeng Yeau-Ren , Mendy Andrew E. , Ko Chi-Tse , Tseng Shih-Feng , Yang Chii-Rong
Published: March 2021

A triboelectric generator (TEG) is a simple coupling combined with triboelectrification and electrostatic induction, which can convert mechanical energy into electrical energy and have the potential for self-powered device application. In this study, TEGs are fabricated consisting of a conductive textile (CT) layer (a fabric woven with polyester and stainless steel) and a polydimethylsiloxane (PDMS) layer. The CT friction layer is also used as a conductive electrode and designed with various surface morphologies, including unpatterned, dots, and lines with 1 and 2 cm spacings. Experimental results show that the TEG with an unpatterned CT layer produces an output voltage of 54.6 V and an output current of 5.46 µA. The patterned surfaces increase the effective contact area and friction effect between the CT and PDMS layers and hence enhance the output voltage and current to 94.4 V and 9.44 µA. Compared to the unpatterned CT layer, the pattern use of 1 cm spaced lines, 2 cm spaced lines, and dots improves the output voltage and current by 1.73, 1.68, and 1.24 times, respectively. Moreover, the TEG with 1 cm spaced lines generates a high output power density of 181.9 mW/m2.
An Optimal Control Problem by a Hybrid System of Hyperbolic and Ordinary Differential Equations
Authors: Arguchintsev Alexander , Poplevko Vasilisa
Published: March 2021

This paper deals with an optimal control problem for a linear system of first-order hyperbolic equations with a function on the right-hand side determined from controlled bilinear ordinary differential equations. These ordinary differential equations are linear with respect to state functions with controlled coefficients. Such problems arise in the simulation of some processes of chemical technology and population dynamics. Normally, general optimal control methods are used for these problems because of bilinear ordinary differential equations. In this paper, the problem is reduced to an optimal control problem for a system of ordinary differential equations. The reduction is based on non-classic exact increment formulas for the cost-functional. This treatment allows to use a number of efficient optimal control methods for the problem. An example illustrates the approach.
Mechanisms of Impact of Blue Spaces on Human Health: A Systematic Literature Review and Meta-Analysis
Authors: Georgiou Michail , Morison Gordon , Smith Niamh , Tieges Zoë , Chastin Sebastien
Published: March 2021

Blue spaces have been found to have significant salutogenic effects. However, little is known about the mechanisms and pathways that link blue spaces and health. The purpose of this systematic review and meta-analysis is to summarise the evidence and quantify the effect of blue spaces on four hypothesised mediating pathways: physical activity, restoration, social interaction and environmental factors. Following the PRISMA guidelines, a literature search was conducted using six databases (PubMed, Scopus, PsycInfo, Web of Science, Cochrane Library, EBSCOHOST/CINAHL). Fifty studies were included in our systematic review. The overall quality of the included articles, evaluated with the Qualsyst tool, was judged to be very good, as no mediating pathway had an average article quality lower than 70%. Random-effects meta-analyses were conducted for physical activity, restoration and social interaction. Living closer to blue space was associated with statistically significantly higher physical activity levels (Cohen’s d = 0.122, 95% CI: 0.065, 0.179). Shorter distance to blue space was not associated with restoration (Cohen’s d = 0.123, 95% CI: −0.037, 0.284) or social interaction (Cohen’s d = −0.214, 95% CI: −0.55, 0.122). Larger amounts of blue space within a geographical area were significantly associated with higher physical activity levels (Cohen’s d = 0.144, 95% CI: 0.024, 0.264) and higher levels of restoration (Cohen’s d = 0.339, 95% CI: 0.072, 0.606). Being in more contact with blue space was significantly associated with higher levels of restoration (Cohen’s d = 0.191, 95% CI: 0.084, 0.298). There is also evidence that blue spaces improve environmental factors, but more studies are necessary for meta-analyses to be conducted. Evidence is conflicting on the mediating effects of social interaction and further research is required on this hypothesised pathway. Blue spaces may offer part of a solution to public health concerns faced by growing global urban populations.
Moderating Effect of the Power–Distance Belief on the Relationship between Employees’ Service Failures and Customers’ Behavioral Outcomes in the Sport Service Industry
Authors: Song Hyunseok , Byon Kevin K.
Published: March 2021

This study was designed to examine the moderating effects of the power–distance belief (PDB) on the relationship between employees’ service failures and customers’ transactional and non-transactional outcomes in a fitness center context. To test the relationships among these variables, we employed two pretests and a main experiment. In Pretest 1, a critical incident technique (CIT) was used to identify the employees’ service failure situations in fitness centers. Then, in Pretest 2, we developed two written scenarios that described employees’ service failures according to low and high severity and confirmed the differences between these two scenarios with a manipulation check. In the main experiment, we employed scenarios to examine the relationships among service failures’ severity, PDB, and customers’ non-transactional and transactional outcomes. We used Hayes’ PROCESS macro to test the PDB’s single moderating effect on the relationship between the service failures’ severity and the customers’ responses. According to the results, the moderating effect on the relationship between the service failures’ severity and fitness center customers’ non-transactional and transactional behaviors was confirmed. We extended the understanding of fitness center customers’ reactions, depending upon individual PDB to service failures, by comparing low- and high-service failure situations. Our findings also suggest that segmenting fitness center customers may help managers recognize that their customers’ varying responses depend on PDB.
Factors Associated with Dental Service Use Based on the Andersen Model: A Systematic Review
Authors: Hajek André , Kretzler Benedikt , König Hans-Helmut
Published: March 2021

Background: A systematic review synthesizing studies examining the determinants of dental service use drawing on the (extended) Andersen model is lacking. Hence, our purpose was to fill this knowledge gap; Methods: Three established electronic databases (PubMed, PsycInfo, as well as CINAHL) were searched. Observational studies focusing on the determinants of dental service use drawing on the Andersen model were included; Results: In sum, 41 studies have been included (ten studies investigating children/adolescents and 31 studies investigating adults). Among children, particularly higher age (predisposing characteristic), higher income (enabling resource) and more oral health problems (need factor) were associated with increased dental service use. Among adults, findings are, in general, less consistent. However, it should be noted that one half of the studies found an association between increased education (predisposing characteristic) and increased dental service. In general, study quality was rather high. However, it should be noted that most studies did not report how they dealt with missing data; Conclusions: Our systematic review revealed that all components (i.e., predisposing characteristics, enabling resources and need factors) of the Andersen model tend to be associated with dental service use among children, whereas the findings are more mixed among adults. In conclusion, beyond need factors, dental service use also tend to be driven by other factors. This may indicate over—or, more likely—underuse of dental services and could enrich the inequality discussion in dental services research.
The Negative Impact of Parental Smoking on Adolescents’ Health-Promoting Behaviors: A Cross-Sectional Study
Authors: Chen Mei-Yen
Published: March 2021

The literature has indicated that adolescents’ exposure to secondhand smoke (SHS) and having smoking parents were positively associated with current tobacco smoking. Few studies have explored the association between parental smoking and adolescent’s health-promoting behaviors. This study aimed to examine the prevalence of SHS and the relationship between parental smoking at home and adolescent’s health-promoting behaviors in rural areas. Methods: A school-based and cross-sectional study was conducted from March to December 2019 in western coastal Yunlin County, Taiwan. A total of 1227 adolescents, including 51% boys, anonymously participated in this study. Three parental smoking situations and eight questions of adolescents’ habits extracted from previous studies were applied. A linear regression model was used to analyze the factors associated with adopting health-promoting behaviors. Results: More than half (67.7%) of adolescents experienced parental smoking at home, 90.2% reported their family smoked around them, and 48.8% of participants “sometimes” or “never” avoided SHS. Many participants showed a low frequency of water (49.6%), vegetable (49.1%), and fruit (63.2%) intake, using dental floss (84.7%), and regular exercise (60.6%). The determinants of adolescents’ health-promoting scores were highly associated with avoidance of SHS, less associated with parental smoking, and parents smoking at home and around adolescents. Conclusion: The findings showed that in the rural area, a high prevalence of parental smoking at home and parental smoking around adolescents was noted. It is an important issue that parental smoking was negatively associated with adolescent’s health-promoting behaviors.
Optimal Application of Forced Air Warming to Prevent Peri-Operative Hypothermia during Abdominal Surgery: A Systematic Review and Meta-Analysis
Authors: Lee Yoonyoung , Kim Kisook
Published: March 2021

Patients who undergo abdominal surgery under general anesthesia develop hypothermia in 80–90% of the cases within an hour after induction of anesthesia. Side effects include shivering, bleeding, and infection at the surgical site. However, the surgical team applies forced air warming to prevent peri-operative hypothermia, but these methods are insufficient. This study aimed to confirm the optimal application method of forced air warming (FAW) intervention for the prevention of peri-operative hypothermia during abdominal surgery. A systematic review and meta-analysis were conducted to provide a synthesized and critical appraisal of the studies included. We used PubMed, EMBASE, CINAHL, and Cochrane Library CENTRAL to systematically search for randomized controlled trials published through March 2020. Twelve studies were systematically reviewed for FAW intervention. FAW intervention effectively prevented peri-operative hypothermia among patients undergoing both open abdominal and laparoscopic surgery. Statistically significant effect size could not be confirmed in cases of only pre- or peri-operative application. The upper body was the primary application area, rather than the lower or full body. These findings could contribute detailed standards and criteria that can be effectively applied in the clinical field performing abdominal surgery.
Knock-Down of HDAC2 in Human Induced Pluripotent Stem Cell Derived Neurons Improves Neuronal Mitochondrial Dynamics, Neuronal Maturation and Reduces Amyloid Beta Peptides
Authors: Frankowski Harald , Yeboah Fred , Berry Bonnie J. , Kinoshita Chizuru , Lee Michelle , Evitts Kira , Davis Joshua , Kinoshita Yoshito , Morrison Richard S. , Young Jessica E.
Published: March 2021

Histone deacetylase 2 (HDAC2) is a major HDAC protein in the adult brain and has been shown to regulate many neuronal genes. The aberrant expression of HDAC2 and subsequent dysregulation of neuronal gene expression is implicated in neurodegeneration and brain aging. Human induced pluripotent stem cell-derived neurons (hiPSC-Ns) are widely used models for studying neurodegenerative disease mechanisms, but the role of HDAC2 in hiPSC-N differentiation and maturation has not been explored. In this study, we show that levels of HDAC2 progressively decrease as hiPSCs are differentiated towards neurons. This suppression of HDAC2 inversely corresponds to an increase in neuron-specific isoforms of Endophilin-B1, a multifunctional protein involved in mitochondrial dynamics. Expression of neuron-specific isoforms of Endophilin-B1 is accompanied by concomitant expression of a neuron-specific alternative splicing factor, SRRM4. Manipulation of HDAC2 and Endophilin-B1 using lentiviral approaches shows that the knock-down of HDAC2 or the overexpression of a neuron-specific Endophilin-B1 isoform promotes mitochondrial elongation and protects against cytotoxic stress in hiPSC-Ns, while HDAC2 knock-down specifically influences genes regulating mitochondrial dynamics and synaptogenesis. Furthermore, HDAC2 knock-down promotes enhanced mitochondrial respiration and reduces levels of neurotoxic amyloid beta peptides. Collectively, our study demonstrates a role for HDAC2 in hiPSC-neuronal differentiation, highlights neuron-specific isoforms of Endophilin-B1 as a marker of differentiating hiPSC-Ns and demonstrates that HDAC2 regulates key neuronal and mitochondrial pathways in hiPSC-Ns.