bluuebunny/crossref_metadata_2025 huggingface dataset:
Equity at the Ballot Box: Health as a Resource for Political Participation Among Low-Income Workers in Two United States Cities
Authors: McGuire Cydney M. , Gollust Sarah E. , De Marco Molly , Durfee Thomas , Wolfson Julian , Caspi Caitlin E.
Published: January 2021

Objective: The purpose of this study is to identify health resources associated with propensity to vote at the local-level among low-wage workers in two United States. cities. Literature confirms individuals of lower income have a lower propensity of turning out to vote, yet few studies have focused on low-income populations to identify the variation in factors associated with voting within this group. Furthermore, few studies have investigated health and voter turnout at the local-level. In this study, we examine factors related to political participation at the local-level within a low-wage sample, examine mental, physical, behavioral, and social health and their association with voter turnout, and assess if these relationships differ by city.

Methods: We use cross-sectional survey data from a sample of 974 low-wage workers in Minneapolis, MN and Raleigh, NC. We computed descriptive statistics and employed a logistic regression to predict their likelihood of local voter turnout, with the key independent variables being health resources, such as self-rated health, body mass index (BMI), mental disability, smoking status, and health insurance status. We employed a logistic regression fully interacted with a city indicator variable to assess if these associations differed by city.

Results: In both cities, less than 50 percent of respondents reported voting in the last election for mayor or city council. About three-quarters of the sample reported food or housing insecurity and the majority of respondents reported utilizing some government assistance, such as supplemental nutrition programs. BMI greater than 30 was significantly associated with lower likelihood of voter turnout compared to those of lower BMI status (marginal effect = −0.10, p = 0.026). Never smoking or quitting was significantly associated with higher likelihood of voter turnout compared to those who reported being a current smoker (marginal effect = 0.10, p = 0.002). Those with health insurance were significantly more likely to report voting compared to those without any insurance (marginal effect = 0.10, p = 0.022). These results did not significantly differ by city.

Conclusions: Our research suggests low-wage workers face significant health burdens which may impact their propensity to vote at the local-level, and these associations do not significantly vary by city despite demographic and political differences between two jurisdictions.
The Effect of Virtual Reality Technology on the Imagery Skills and Performance of Target-Based Sports Athletes
Authors: Bedir Deniz , Erhan Süleyman Erim
Published: January 2021

The aim of this study is the examination of the effect of virtual reality based imagery (VRBI) training programs on the shot performance and imagery skills of athletes and, and to conduct a comparison with Visual Motor Behavior Rehearsal and Video Modeling (VMBR + VM). In the research, mixed research method and sequential explanatory design were used. In the quantitative dimension of the study the semi-experimental model was used, and in the qualitative dimension the case study design was adopted. The research participants were selected from athletes who were involved in our target sports: curling (n= 14), bowling (n= 13), and archery (n= 7). All participants were randomly assigned to VMBR + VM (n= 11), VRBI (n= 12), and Control (n= 11) groups through the “Research Randomizer” program. The quantitative data of the study was: the weekly shot performance scores of the athletes and the data obtained from the “Movement Imagery Questionnaire-Revised.” The qualitative data was obtained from the data collected from the semi-structured interview guide, which was developed by researchers and field experts. According to the results obtained from the study, there were statistically significant differences between the groups in terms of shot performance and imagery skills. VRBI training athletes showed more improvement in the 4-week period than the athletes in the VMBR + VM group, in terms of both shot performance and imagery skills. In addition, the VRBI group adapted to the imagery training earlier than the VMBR + VM group. As a result, it was seen that they showed faster development in shot performances. From these findings, it can be said that VRBI program is more efficient in terms of shot performance and imagery skills than VMBR + VM, which is the most used imaging training model.
When the Part Mirrors the Whole: Interactions Beyond “Simple Location”
Authors: Gomez-Marin Alex , Arnau Juan
Published: January 2021

Reductionism relies on expectations that it is possible to make sense of the whole by studying its parts, whereas emergentism considers that program to be unattainable, partly due to the existence of emergent properties. The emergentist holistic stance is particularly relevant in biology and cognitive neuroscience, where interactions amongst system components and environment are key. Here we consider Alfred North Whitehead's philosophy as providing important insights to metaphysics of science in general, and to the reductionism vs. emergentism debate in particular. An appraisal of Whitehead's perspective reveals a difficulty shared by both approaches, referred to him as “simple location”: the commitment to the idea that the nature of things is exhausted by their intrinsic or internal properties, and does not take into account relations or dynamic interactions denoting “togetherness.” In a word, that things are simply where they are. Whitehead criticizes this externalist ontological perspective in which each interacting element exists, and can be thought, without essential reference to other elements. The aim of this work is to uncover such a stance, particularly in the context of dynamical systems, and to show its shortcomings. We propose an alternative relational approach based on Whitehead's notion of “internal relations,” which we explicate and illustrate with several examples. Our work aims to criticize the notion of simple location, even in the framework of emergentist accounts, so as to contribute to a “relational turn” that will conceive “inter-identities” as “intra-identities” in which interactants are not enduring substances, but internally related processes. In sum, we argue that the notion of internal relations has a strong theoretical power to overcome some fundamental difficulties in the study of life and mind.
Traditional Sports and Games: Intercultural Dialog, Sustainability, and Empowerment
Authors: Saura Soraia Chung , Zimmermann Ana Cristina
Published: January 2021

From Traditional Sports and Games (TSG) we have not only learned different ways of living time as well as inhabit space and a particular mode of practicing sports and games from distinct cultures, but also promoting universal dialog among people. TSG presents sustainable and ecological references for living needed even before the advent of the COVID-19 pandemic. Nowadays, environmentally friendly policies and production methods must be taken more seriously. TSG may reveal a path to sustainable development, considering our corporeality and cultural diversity. TSG are expressions of human groups that historically reproduce their way of life-based on modes of social cooperation and specific forms of relationship with nature, traditionally characterized by sustained environmental management. The purpose of this article is to discuss how TSG promotes intercultural dialog with a focus on sustainability, and how it empowers people and creates equality among its players. We understand that TSG can break socio-cultural barriers. For this study, we considered data from a Brazilian experience of TSG’s Festival held at a public school in the city of São Paulo (Brazil), organized in collaboration with our study group. Data consists of observations recorded in pictures and films during the processes of organization, preparation, implementation, and evaluation of a TSG Festival, held in a public school in São Paulo, Brazil from the years of 2017 and 2018, with the participation of 800 students from the first to the ninth grade of elementary school, aged between 7 and 17 years. The first step in our analysis is taken from a dynamic called “Talking Circles,” where researchers registered dialog about experiences and used specific literature about TSG, from a philosophical perspective. The team and students from our study group that organized these events were invited to participate in four different Talking Circles. Approximately 20 people participated in each one of these meetings. Recurrences that emerged from these Talking Circles are presented in the results and explored afterward. What does this experience–from bodies in movement, artistic or sporting, or both–teach about intercultural dialog and empowerment? Such gestures indicate a cultural heritage and corporeal wisdom that allows humans to face new encounters and understanding in peace, recognizing humanity common to all of us, regardless of our origins. Ethical and aesthetical results of such dialog reveal possibilities to be explored in our relationship with different cultures and the environment, providing points of sustainable development through TSG.
Perceptual Properties of the Poisson Effect
Authors: Kawabe Takahiro
Published: January 2021

When an elastic material (e.g., fabric) is horizontally stretched (or compressed), the material is compressed (or extended) vertically – so-called the Poisson effect. In the different case of the Poisson effect, when an elastic material (e.g., rubber) is vertically squashed, the material is horizontally extended. In both cases, the visual system receives image deformations involving horizontal expansion and vertical compression. How does the brain disentangle the two cases and accurately distinguish stretching from squashing events? Manipulating the relative magnitude of the deformation of a square between horizontal and vertical dimensions in the two-dimensional stimuli, we asked observers to judge the force direction in the stimuli. Specifically, the participants reported whether the square was stretched or squashed. In general, the participant’s judgment was dependent on the relative deformation magnitude. We also checked the anisotropic effect of deformation direction [i.e., horizontal vs. vertical stretching (or squashing)] and found that the participant’s judgment was strongly biased toward horizontal stretching. We also observed that the asymmetric deformation pattern, which indicated the specific context of force direction, was also a strong cue to the force direction judgment. We suggest that the brain judges the force direction in the Poisson effect on the basis of assumptions about the relationship between image deformation and force direction, in addition to the relative image deformation magnitudes between horizontal and vertical dimensions.
HIIT Models in Addition to Training Load and Heart Rate Variability Are Related With Physiological and Performance Adaptations After 10-Weeks of Training in Young Futsal Players
Authors: Campos Fernando de Souza , Borszcz Fernando Klitzke , Flores Lucinar Jupir Forner , Barazetti Lilian Keila , Teixeira Anderson Santiago , Hartmann Nunes Renan Felipe , Guglielmo Luiz Guilherme Antonacci
Published: January 2021

Introduction

The present study aimed to investigate the effects of two high-intensity interval training (HIIT) shuttle-run-based models, over 10 weeks on aerobic, anaerobic, and neuromuscular parameters, and the association of the training load and heart rate variability (HRV) with the change in the measures in young futsal players.

Methods

Eleven young male futsal players (age: 18.5 ± 1.1 years; body mass: 70.5 ± 5.7 kg) participated in this study. This pre-post study design was performed during a typical 10 weeks training period. HIIT sessions were conducted at 86% (HIIT86; n = 6) and 100% (HIIT100; n = 5) of peak speed of the FIET. Additionally, friendly and official matches, technical-tactical and strength-power training sessions were performed. Before and after the training period, all players performed the FIET, treadmill incremental, repeated sprint ability (RSA), sprint 15-m, and vertical jump tests (CMJ and SJ), and the HRV was measured. Training load (TL) was monitored using the session rating of perceived effort. Data analysis was carried out using Bayesian inference methods.

Results

The HIIT86 model showed clear improvements for the peak oxygen uptake (VO2peak), peak speed in the treadmill incremental test, first and second ventilatory thresholds, RSA best and mean times, CMJ, and SJ. The HIIT100 model presented distinct advances in VO2peak, peak speed in the treadmill incremental test, RSA mean time, and CMJ. Between HIIT models comparisons showed more favorable probabilities of improvement for HIIT86 than HIIT100 model in all parameters. TL data and HIIT models strongly explained the changes in the RSA mean and best times (R2 = 0.71 and 0.87, respectively), as well as HRV changes, and HIIT models explained positively VO2peak changes (R2 = 0.72). All other changes in the parameters were low to moderately explained.

Conclusion

The HIIT86 proved to be more effective for improving aerobic, RSA, and neuromuscular parameters than HIIT100 during a typical 10-week futsal training period. So, strength and conditioning specialists prescribing shuttle-run intermittent exercises at submaximal intensities can manage the individual acceleration load imposed on athlete increasing or decreasing either the set duration or the frequency of change of direction during HIIT programming.
COVID-19 Higher Mortality in Chinese Regions With Chronic Exposure to Lower Air Quality
Authors: Pansini Riccardo , Fornacca Davide
Published: January 2021

We investigated the geographical character of the COVID-19 infection in China and correlated it with satellite- and ground-based measurements of air quality. Controlling for population density, we found more viral infections in those prefectures (U.S. county equivalent) afflicted by high Carbon Monoxide, Formaldehyde, PM 2.5, and Nitrogen Dioxide values. Higher mortality was also correlated with relatively poor air quality. When summarizing the results at a greater administrative level, we found that the 10 provinces (U.S. state equivalent) with the highest rate of mortality by COVID-19, were often the most polluted but not the most densely populated. Air pollution appears to be a risk factor for the incidence of this disease, despite the conventionally apprehended influence of human mobility on disease dynamics from the site of first appearance, Wuhan. The raw correlations reported here should be interpreted in a broader context, accounting for the growing evidence reported by several other studies. These findings warn communities and policymakers on the implications of long-term air pollution exposure as an ecological, multi-scale public health issue.
Evidence-Driven Approach for Assessing Social Vulnerability and Equality During Extreme Climatic Events
Authors: Barankin Ram A. , Portman Michelle E. , Kirshen Paul , Bowen Robert E.
Published: January 2021

Climate change adaptation policy requires assessing a community's vulnerability based on its socio-economic characteristics. A predominant approach to vulnerability assessment is indicator-based, wherein variables are aggregated to assess the vulnerability of units in a system (e.g., neighborhoods in a city). Here we show that a particular evidence-based predictive statistics approach can address two shortcomings of the most commonly-used indicator-based approach: lack of a means of validation and problematic weighting of individual indicators. We demonstrate how robust evidence-based models can produce frameworks that overcome these limitations. Using the case study of Hurricane Sandy in the State of New Jersey, we conducted two-pronged validated vulnerability assessments, based on insurance claim payouts and assistance grants. The latter needs-based assessment shows that “Minorities” are substantially more vulnerable than others based on a significant negative association with assistance approval rate (approved claims divided by all claims). Our findings highlight issues discussed in the literature within the context of climate justice and equity. Such an approach is helpful locally, but also when adaptation plans are developed over broad scales of time and space considering disparities between regions or across multiple jurisdictions.
Little Difference in Milk Fatty Acid and Terpene Composition Among Three Contrasting Dairy Breeds When Grazing a Biodiverse Mountain Pasture
Authors: Koczura Madeline , Martin Bruno , Musci Marilena , Massimo Martina Di , Bouchon Matthieu , Turille Germano , Kreuzer Michael , Berard Joel , Coppa Mauro
Published: January 2021

In the mountains, autochthonous and robust breeds are often used to valorize biodiverse grasslands. Along with their lower nutrient requirements, compared to specialized dairy breeds, they are expected to be better adapted to complex environments and valorize grasslands into dairy products of high quality. Therefore, the aim of the present study was to investigate the grazing selection of three contrasting dairy breeds on a biodiverse mountain pasture, and its consequences on milk fatty acid (FA) profile and prevalence of individual terpenes. A dual-purpose breed from the Italian Alps, the Valdostana Red Pied (Va), was compared to Montbéliardes (Mo), more specialized in milk production, and the highly specialized Holsteins (Ho). Diet selection was measured by scan-sampling, calculating selectivity indexes, and collecting simulated bites during two consecutive days in June (end of first grazing cycle) and July (second grazing cycle). Milk samples were collected at each milking during these experimental periods. Yield of milk and its fat and protein contents were measured. Milk FA and terpenes were analyzed by gas chromatographic methods. We tested the effects of breed, period and their interaction in a repeated mixed model, and calculated Pearson's correlations between behavioral data and milk FA as well as terpenes. The Va grazed less mature vegetation than Ho, but this difference was not sufficient to lead to a major breed effect on milk FA profile and prevalence of terpenes. However, the proportion of α-linolenic acid (C18:3 n-3) was always higher in the milk fat of Va than Ho (Mo were intermediary), but this without any correlation to grazing selection. This could be a consequence from a different metabolism concerning ruminal biohydrogenation, but must be further investigated. Finally, we confirmed previous studies that highlighted a link between milk quality and cows' grazing behavior, but here without differences among breeds. All cows adapted their behavior to the herbage evolution during the season, leading to higher proportions of unsaturated FA in July than June milks. Our study suggests that under mountain grazing conditions (biodiverse pasture and cows in late lactation), milk quality depends more on herbage composition than on cow breed.
Assessment of TAF, METAR, and SPECI Reports Based on ICAO ANNEX 3 Regulation
Authors: Novotny Josef , Dejmal Karel , Repal Vladimir , Gera Martin , Sladek David
Published: January 2021

The Terminal Aerodrome Forecast (TAF) is one of the most prominent and widely accepted forecasting tools for flight planning. The reliability of this instrument is crucial for its practical applicability, and its quality may further affect the overall air transport safety and economic efficiency. The presented study seeks to objectify the assessment of the success rate of TAFs in the full breadth of their scope, unlike alternative approaches that typically analyze one selected element. It aspires to submit a complex survey on TAF realization in the context of ANNEX 3 (a regulation for Meteorological Service for International Air Navigation issued by the International Civil Aviation Organization (ICAO)) defined methodology and to provoke a discussion on the clarification and completion of ANNEX 3. Moreover, the adherence of TAFs to ICAO ANNEX 3 (20th Edition) is examined and presented on the example of reports issued in the Czech Republic. The study evaluates the accuracy of TAF forecast verified by Aerodrome Routine Meteorological Report (METAR) and Special Meteorological Report (SPECI), whose quality was assessed first. The required accuracy of TAFs was achieved for most evaluated stations. A discrepancy in terms of formal structure between actually issued reports and the ANNEX 3 defined form was revealed in over 90% of reports. The study identifies ambiguities and contradictions contained in ANNEX 3 that lead to loose interpretations of its stipulations and complicate the objectification of TAF evaluation.
The Mitochondrial Citrate Carrier SLC25A1/CIC and the Fundamental Role of Citrate in Cancer, Inflammation and Beyond
Authors: Mosaoa Rami , Kasprzyk-Pawelec Anna , Fernandez Harvey R. , Avantaggiati Maria Laura
Published: January 2021

The mitochondrial citrate/isocitrate carrier, CIC, has been shown to play an important role in a growing list of human diseases. CIC belongs to a large family of nuclear-encoded mitochondrial transporters that serve the fundamental function of allowing the transit of ions and metabolites through the impermeable mitochondrial membrane. Citrate is central to mitochondrial metabolism and respiration and plays fundamental activities in the cytosol, serving as a metabolic substrate, an allosteric enzymatic regulator and, as the source of Acetyl-Coenzyme A, also as an epigenetic modifier. In this review, we highlight the complexity of the mechanisms of action of this transporter, describing its involvement in human diseases and the therapeutic opportunities for targeting its activity in several pathological conditions.
Liraglutide-Induced Hepatotoxicity
Authors: Maor Yaakov , Ergaz David , Malnick Stephen D. H. , Melzer Ehud , Neuman Manuela G.
Published: January 2021

A 52-year-old woman with a BMI of 31.2 kg/m2 was treated with the glucagon-like peptide 1 (GLP-1) agonist liraglutide as part of her weight-reduction program. Following this, she developed an idiosyncratic drug-related liver injury (IDILI). Advances in noninvasive techniques enabled this diagnosis to be established. By employing easily quantifiable methods based on serum biomarkers, we could explore a wide variety of endpoints in assessing personalized DILI. In addition, we can test endpoints that are associated with the drug’s mechanism of action. Personalized medicine and therapeutic pharmacovigilance of incretin-based hypoglycemic agents are needed to ensure the safety of patients.
Transcranial Evoked Potentials Can Be Reliably Recorded with Active Electrodes
Authors: Mancuso Marco , Sveva Valerio , Cruciani Alessandro , Brown Katlyn , Ibáñez Jaime , Rawji Vishal , Casula Elias , Premoli Isabella , D'Ambrosio Sasha , Rothwell John , Rocchi Lorenzo
Published: January 2021

Electroencephalographic (EEG) signals evoked by transcranial magnetic stimulation (TMS) are usually recorded with passive electrodes (PE). Active electrode (AE) systems have recently become widely available; compared to PE, they allow for easier electrode preparation and a higher-quality signal, due to the preamplification at the electrode stage, which reduces electrical line noise. The performance between the AE and PE can differ, especially with fast EEG voltage changes, which can easily occur with TMS-EEG; however, a systematic comparison in the TMS-EEG setting has not been made. Therefore, we recorded TMS-evoked EEG potentials (TEPs) in a group of healthy subjects in two sessions, one using PE and the other using AE. We stimulated the left primary motor cortex and right medial prefrontal cortex and used two different approaches to remove early TMS artefacts, Independent Component Analysis and Signal Space Projection—Source Informed Recovery. We assessed statistical differences in amplitude and topography of TEPs, and their similarity, by means of the concordance correlation coefficient (CCC). We also tested the capability of each system to approximate the final TEP waveform with a reduced number of trials. The results showed that TEPs recorded with AE and PE do not differ in amplitude and topography, and only few electrodes showed a lower-than-expected CCC between the two methods of amplification. We conclude that AE are a viable solution for TMS-EEG recording.
Soluble PD-1 but Not PD-L1 Levels Predict Poor Outcome in Patients with High-Risk Diffuse Large B-Cell Lymphoma
Authors: Vajavaara Heli , Mortensen Julie Bondgaard , Leivonen Suvi-Katri , Hansen Ida Monrad , Ludvigsen Maja , Holte Harald , Jørgensen Judit , Bjerre Mette , d’Amore Francesco , Leppä Sirpa
Published: January 2021

Interaction of checkpoint receptor programmed death 1 (PD-1) with its ligand 1 (PD-L1) downregulates T cell effector functions and thereby leads to tumor immune escape. Here, we aimed to determine the clinical significance of soluble PD-1 (sPD-1) and soluble PD-L1 (sPD-L1) in patients with diffuse large B-cell lymphoma (DLBCL). We included 121 high-risk DLBCL patients treated in the Nordic NLG-LBC-05 trial with dose-dense immunochemotherapy. sPD-1 and sPD-L1 levels were measured from serum samples collected prior to treatment, after three immunochemotherapy courses, and at the end of therapy. sPD-1 and sPD-L1 levels were the highest in pretreatment samples, declining after three courses, and remaining low post-treatment. Pretreatment sPD-1 levels correlated with the quantities of PD1+ T cells in tumor tissue and translated to inferior survival, while no correlation was observed between sPD-L1 levels and outcome. The relative risk of death was 2.9-fold (95% CI 1.12–7.75, p = 0.028) and the risk of progression was 2.8-fold (95% CI 1.16–6.56, p = 0.021) in patients with high pretreatment sPD-1 levels compared to those with low levels. In conclusion, pretreatment sPD-1 level is a predictor of poor outcome after dose-dense immunochemotherapy and may be helpful in further improving molecular risk profiles in DLBCL.
Testing Lab-on-a-Chip Technology for Culturing Human Melanoma Cells under Simulated Microgravity
Authors: Przystupski Dawid , Górska Agata , Michel Olga , Podwin Agnieszka , Śniadek Patrycja , Łapczyński Radosław , Saczko Jolanta , Kulbacka Julita
Published: January 2021

The dynamic development of the space industry makes space flights more accessible and opens up new opportunities for biological research to better understand cell physiology under real microgravity. Whereas specialized studies in space remain out of our reach, preliminary experiments can be performed on Earth under simulated microgravity (sµg). Based on this concept, we used a 3D-clinostat (3D-C) to analyze the effect of short exposure to sµg on human keratinocytes HaCaT and melanoma cells A375 cultured on all-glass Lab-on-a-Chip (LOC). Our preliminary studies included viability evaluation, mitochondrial and caspase activity, and proliferation assay, enabling us to determine the effect of sµg on human cells. By comparing the results concerning cells cultured on LOCs and standard culture dishes, we were able to confirm the biocompatibility of all-glass LOCs and their potential application in microgravity research on selected human cell lines. Our studies revealed that HaCaT and A375 cells are susceptible to simulated microgravity; however, we observed an increased caspase activity and a decrease of proliferation in cancer cells cultured on LOCs in comparison to standard cell cultures. These results are an excellent basis to conduct further research on the possible application of LOCs systems in cancer research in space.
Changing Incidence and Survival of Primary Central Nervous System Lymphoma in Australia: A 33-Year National Population-Based Study
Authors: Farrall Alexandra L. , Smith Justine R.
Published: January 2021

Primary central nervous system lymphoma (PCNSL) is a rare brain cancer that remains challenging to study. Epidemiology of PCNSL in the Australian population, which is racially and ethnically diverse, has not been examined previously. Using ICD-O-3.1 Morphology and Topography Codes to identify cases, we analyzed complete datasets from the comprehensive Australian Cancer Database (1982–2014, adults aged ≥ 20 years) to establish incidence rates and trends of PCNSL, and to define survival outcomes of individuals diagnosed with PCNSL, including the predominant diffuse large B-cell lymphoma (DLBCL) type. Age-standardized incidence of PCNSL increased by an average annual 6.8% percent over the study period, with current incidence of 0.43 (95% confidence interval, 0.41–0.46) per 100,000 person-years, in comparison to 21.89 (21.41–22.38) per 100,000 person-years for non-CNS lymphoma. Increase in incidence was characterized by an acute rise between 1996 and 1999, was more pronounced with increasing age, and was driven by increasing incidence of DLBCL. Overall survival for persons diagnosed with PCNSL improved significantly across the study period, with 5-year survival probability increasing from 0.21 (95% confidence interval, 0.16–0.26) to 0.33 (0.30–0.36), and median survival increasing from 318 to 600 days, between 1982–1999 and 2000–2014. Increase in survival was significantly higher for persons with DLBCL versus non-DLBCL PCNSL, but substantially lower than that for persons with non-CNS lymphoma, who had a 5-year survival probability of 0.62 (0.62–0.62) and a median survival of 3388 days in 2000–2014. This study links increasing incidence of PCNSL in Australia to increasing incidence of DLCBL, including in younger adults, and highlights the improving, but low, survival outcome of this cancer.
Chimeric Antigen Receptor beyond CAR-T Cells
Authors: Qin Vicky Mengfei , D’Souza Criselle , Neeson Paul J. , Zhu Joe Jiang
Published: January 2021

Chimeric antigen receptors (CAR) are genetically engineered receptors that can recognise specific antigens and subsequently activate downstream signalling. Human T cells engineered to express a CAR, also known as CAR-T cells, can target a specific tumour antigen on the cell surface to mediate a cytotoxic response against the tumour. CAR-T cell therapy has achieved remarkable success in treating hematologic malignancies, but not in solid tumours. Currently, extensive research is being carried out to make CAR-T cells a therapy for solid tumours. To date, most of the research interest in the field has focused on cytotoxic T lymphocytes as the carrier of CAR products. However, in addition to T cells, the CAR design can be introduced in other immune cells, such as natural killer (NK)/NKT cells, γδ T cells, mucosal-associated invariant T (MAIT) cells, dendritic cells (DC), macrophages, regulatory T cells (Treg), B cells, etc. Some of the CAR-engineered immune cells, such as CAR- γδ T and CAR-NK/NK-T cells, are directly involved in the anti-tumour response, demonstrated in preclinical studies and/or clinical trials. CAR-Tregs showed promising therapeutic potential in treating autoimmune diseases. In particular, B cells engineered with chimeric receptors can be used as a platform for long-term delivery of therapeutic proteins, such as recombinant antibodies or protein replacement, in an antigen-specific manner. CAR technology is one of the most powerful engineering platforms in immunotherapy, especially for the treatment of cancers. In this review, we will discuss the recent application of the CAR design in non-CAR-T cells and future opportunities in immunotherapy.
Specific Inhibition of HIF Activity: Can Peptides Lead the Way?
Authors: Mylonis Ilias , Chachami Georgia , Simos George
Published: January 2021

Reduced oxygen availability (hypoxia) is a characteristic of many disorders including cancer. Central components of the systemic and cellular response to hypoxia are the Hypoxia Inducible Factors (HIFs), a small family of heterodimeric transcription factors that directly or indirectly regulate the expression of hundreds of genes, the products of which mediate adaptive changes in processes that include metabolism, erythropoiesis, and angiogenesis. The overexpression of HIFs has been linked to the pathogenesis and progression of cancer. Moreover, evidence from cellular and animal models have convincingly shown that targeting HIFs represents a valid approach to treat hypoxia-related disorders. However, targeting transcription factors with small molecules is a very demanding task and development of HIF inhibitors with specificity and therapeutic potential has largely remained an unattainable challenge. Another promising approach to inhibit HIFs is to use peptides modelled after HIF subunit domains known to be involved in protein–protein interactions that are critical for HIF function. Introduction of these peptides into cells can inhibit, through competition, the activity of endogenous HIFs in a sequence and, therefore also isoform, specific manner. This review summarizes the involvement of HIFs in cancer and the approaches for targeting them, with a special focus on the development of peptide HIF inhibitors and their prospects as highly-specific pharmacological agents.
The lncRNA H19-Derived MicroRNA-675 Promotes Liver Necroptosis by Targeting FADD
Authors: Harari-Steinfeld Rona , Gefen Maytal , Simerzin Alina , Zorde-Khvalevsky Elina , Rivkin Mila , Ella Ezra , Friehmann Tomer , Gerlic Mordechay , Zucman-Rossi Jessica , Caruso Stefano , Leveille Mélissa , Estall Jennifer L. , Goldenberg Daniel S. , Giladi Hilla , Galun Eithan , Bromberg Zohar
Published: January 2021

The H19-derived microRNA-675 (miR-675) has been implicated as both tumor promoter and tumor suppressor and also plays a role in liver inflammation. We found that miR-675 promotes cell death in human hepatocellular carcinoma (HCC) cell lines. We show that Fas-associated protein with death domain (FADD), a mediator of apoptotic cell death signaling, is downregulated by miR-675 and a negative correlation exists between miR-675 and FADD expression in mouse models of HCC (p = 0.014) as well as in human samples (p = 0.017). We demonstrate in a mouse model of liver inflammation that overexpression of miR-675 promotes necroptosis, which can be inhibited by the necroptosis-specific inhibitor Nec-1/Nec-1s. miR-675 induces the level of both p-MLKL (Mixed Lineage Kinase Domain-Like Pseudokinase) and RIP3 (receptor-interacting protein 3), which are key signaling molecules in necroptosis, and enhances MLKL binding to RIP3. miR-675 also inhibits the levels of cleaved caspases 8 and 3, suggesting that miR-675 induces a shift from apoptosis to a necroptotic cellular pathway. In conclusion, downregulation of FADD by miR-675 promotes liver necroptosis in response to inflammatory signals. We propose that this regulation cascade can stimulate and enhance the inflammatory response in the liver, making miR-675 an important regulator in liver inflammation and potentially also in HCC.
Lack of Electron Acceptors Contributes to Redox Stress and Growth Arrest in Asparagine-Starved Sarcoma Cells
Authors: Bauer Christoph , Quante Meret , Breunis Willemijn B. , Regina Carla , Schneider Michaela , Andrieux Geoffroy , Gorka Oliver , Groß Olaf , Boerries Melanie , Kammerer Bernd , Hettmer Simone
Published: January 2021

Amino acids are integral components of cancer metabolism. The non-essential amino acid asparagine supports the growth and survival of various cancer cell types. Here, different mass spectrometry approaches were employed to identify lower aspartate levels, higher aspartate/glutamine ratios and lower tricarboxylic acid (TCA) cycle metabolite levels in asparagine-deprived sarcoma cells. Reduced nicotinamide adenine dinucleotide (NAD+)/nicotinamide adenine dinucleotide hydride (NADH) ratios were consistent with redirection of TCA cycle flux and relative electron acceptor deficiency. Elevated lactate/pyruvate ratios may be due to compensatory NAD+ regeneration through increased pyruvate to lactate conversion by lactate dehydrogenase. Supplementation with exogenous pyruvate, which serves as an electron acceptor, restored aspartate levels, NAD+/NADH ratios, lactate/pyruvate ratios and cell growth in asparagine-deprived cells. Chemicals disrupting NAD+ regeneration in the electron transport chain further enhanced the anti-proliferative and pro-apoptotic effects of asparagine depletion. We speculate that reductive stress may be a major contributor to the growth arrest observed in asparagine-starved cells.
Targeting the Sonic Hedgehog Pathway to Suppress the Expression of the Cancer Stem Cell (CSC)—Related Transcription Factors and CSC-Driven Thyroid Tumor Growth
Authors: Lu Yurong , Zhu Yiwen , Deng Shihan , Chen Yuhuang , Li Wei , Sun Jing , Xu Xiulong
Published: January 2021

The sonic hedgehog (Shh) pathway plays important roles in tumorigenesis, tumor growth, drug resistance, and metastasis. We and others have reported earlier that this pathway is highly activated in thyroid cancer. However, its role in thyroid cancer stem cell (CSC) self-renewal and tumor development remains incompletely understood. B lymphoma Mo-MLV insertion region 1 homolog (BMI1) and SRY-Box Transcription Factor 2 (SOX2) are two CSC-related transcription factors that have been implicated in promoting CSC self-renewal. The objective of our current investigation was to determine the role of the Shh pathway in regulating BMI1 and SOX2 expression in thyroid cancer and promoting thyroid tumor growth and development. Here we report that inhibition of the Shh pathway by Gli1 siRNA or by cyclopamine and GANT61 reduced BMI1 and SOX2 expression in SW1736 and KAT-18 cells, two anaplastic thyroid cancer cell lines. The opposite results were obtained in cells overexpressing Gli1 or its downstream transcription factor Snail. The Shh pathway regulated SOX2 and BMI1 expression at a transcriptional and post-transcriptional level, respectively. GANT61 treatment suppressed the growth of SW1736 CSC-derived tumor xenografts but did not significantly inhibit the growth of tumors grown from bulk tumor cells. Clinicopathological analyses of thyroid tumor specimens by immunohistochemical (IHC) staining revealed that BMI1 and SOX2 were highly expressed in thyroid cancer and correlated with Gli1 expression. Our study provides evidence that activation of the Shh pathway leads to increased BMI1 and SOX2 expression in thyroid cancer and promotes thyroid CSC-driven tumor initiation. Targeting the Shh pathway may have therapeutic value for treating thyroid cancer and preventing recurrence.
Pattern Recognition of Development Stage of Creepage Discharge of Oil–Paper Insulation under AC–DC Combined Voltage Based on OS-ELM
Authors: Jin Fubao , Zhang Shanjun , Zhou Yuanxiang
Published: January 2021

The recognition of the creepage discharge development process of oil–paper insulation under AC–DC combined voltage is the basis for fault monitoring and diagnosis of converter transformers; however, only a few related studies are available. In this study, the AC–DC combined voltage with a ratio of 1:1 was used to develop a recognition method for the creepage discharge development process of an oil–paper insulation under a cylinder–plate electrode structure. First, the pulse current method was used to collect the discharge signals in the creepage discharge development process. Then, 24 characteristic parameters were extracted from four types of creepage discharge characteristic spectra after dimensionality reduction. Finally, based on the online sequential extreme learning machine (OS-ELM) algorithm, these characteristic parameters were used to recognize the development stage of the creepage discharge of the oil–paper insulation. The results showed that when the size of the sample training set used in the OS-ELM algorithm is close to the number of hidden layer neurons, a high recognition accuracy can be obtained, and the type of activation function has little influence on the recognition accuracy. Four stages of the creepage discharge development process were recognized using the OS-ELM algorithm; the trend was the same as that of the characteristic parameters of the entire creepage discharge development process. The recognition accuracy was 91.4%. The algorithm has a high computing speed and high accuracy and can train data in batches. Therefore, it can be widely used in the field of online monitoring and evaluation of electrical equipment status.
Projections for Mexico’s Tropical Rainforests Considering Ecological Niche and Climate Change
Authors: Santos-Hernández Antonio Fidel , Monterroso-Rivas Alejandro Ismael , Granados-Sánchez Diódoro , Villanueva-Morales Antonio , Santacruz-Carrillo Malinali
Published: January 2021

The tropical rainforest is one of the lushest and most important plant communities in Mexico’s tropical regions, yet its potential distribution has not been studied in current and future climate conditions. The aim of this paper was to propose priority areas for conservation based on ecological niche and species distribution modeling of 22 species with the greatest ecological importance at the climax stage. Geographic records were correlated with bioclimatic temperature and precipitation variables using Maxent and Kuenm software for each species. The best Maxent models were chosen based on statistical significance, complexity and predictive power, and current potential distributions were obtained from these models. Future potential distributions were projected with two climate change scenarios: HADGEM2_ES and GFDL_CM3 models and RCP 8.5 W/m2 by 2075–2099. All potential distributions for each scenario were then assembled for further analysis. We found that 14 tropical rainforest species have the potential for distribution in 97.4% of the landscape currently occupied by climax vegetation (0.6% of the country). Both climate change scenarios showed a 3.5% reduction in their potential distribution and possible displacement to higher elevation regions. Areas are proposed for tropical rainforest conservation where suitable bioclimatic conditions are expected to prevail.
Spectral Early-Warning Signals for Sudden Changes in Time-Dependent Flow Patterns
Authors: Ndour Moussa , Padberg-Gehle Kathrin , Rasmussen Martin
Published: January 2021

Lagrangian coherent sets are known to crucially determine transport and mixing processes in non-autonomous flows. Prominent examples include vortices and jets in geophysical fluid flows. Coherent sets can be identified computationally by a probabilistic transfer-operator-based approach within a set-oriented numerical framework. Here, we study sudden changes in flow patterns that correspond to bifurcations of coherent sets. Significant changes in the spectral properties of a numerical transfer operator are heuristically related to critical events in the phase space of a time-dependent system. The transfer operator approach is applied to different example systems of increasing complexity. In particular, we study the 2002 splitting event of the Antarctic polar vortex.
Numerical Simulation of Dynamic Fluid-Structure Interaction with Elastic Structure–Rigid Obstacle Contact
Authors: Yakhlef Othman , Murea Cornel Marius
Published: January 2021

An implicit scheme by partitioned procedures is proposed to solve a dynamic fluid–structure interaction problem in the case when the structure displacements are limited by a rigid obstacle. For the fluid equations (Sokes or Navier–Stokes), the fictitious domain method with penalization was used. The equality of the fluid and structure velocities at the interface was obtained using the penalization technique. The surface forces at the fluid–structure interface were computed using the fluid solution in the structure domain. A quadratic optimization problem with linear inequalities constraints was solved to obtain the structure displacements. Numerical results are presented.
Identification of Variants (rs11571707, rs144848, and rs11571769) in the BRCA2 Gene Associated with Hereditary Breast Cancer in Indigenous Populations of the Brazilian Amazon
Authors: Dobbin Elizabeth Ayres Fragoso , Medeiros Jéssyca Amanda Gomes , Costa Marta Solange Camarinha Ramos , Rodrigues Juliana Carla Gomes , Guerreiro João Farias , Kroll José Eduardo , Souza Sandro José de , de Assumpção Paulo Pimentel , Ribeiro-dos-Santos Ândrea , Santos Sidney Emanuel Batista dos , Burbano Rommel Mario Rodríguez , Fernandes Marianne Rodrigues , Santos Ney Pereira Carneiro dos
Published: January 2021

Estimates show that 5–10% of breast cancer cases are hereditary, caused by genetic variants in autosomal dominant genes; of these, 16% are due to germline mutations in the BRCA1 and BRCA2 genes. The comprehension of the mutation profile of these genes in the Brazilian population, particularly in Amazonian Amerindian groups, is scarce. We investigated fifteen polymorphisms in the BRCA1 and BRCA2 genes in Amazonian Amerindians and compared the results with the findings of global populations publicly available in the 1000 Genomes Project database. Our study shows that three variants (rs11571769, rs144848, and rs11571707) of the BRCA2 gene, commonly associated with hereditary breast cancer, had a significantly higher allele frequency in the Amazonian Amerindian individuals in comparison with the African, American, European, and Asian groups analyzed. These data outline the singular genetic profiles of the indigenous population from the Brazilian Amazon region. The knowledge about BRCA1 and BRCA2 variants is critical to establish public policies for hereditary breast cancer screening in Amerindian groups and populations admixed with them, such as the Brazilian population.
Evaluation of DNA Extraction Methods Developed for Forensic and Ancient DNA Applications Using Bone Samples of Different Age
Authors: Xavier Catarina , Eduardoff Mayra , Bertoglio Barbara , Amory Christina , Berger Cordula , Casas-Vargas Andrea , Pallua Johannes , Parson Walther
Published: January 2021

The efficient extraction of DNA from challenging samples, such as bones, is critical for the success of downstream genotyping analysis in molecular genetic disciplines. Even though the ancient DNA community has developed several protocols targeting small DNA fragments that are typically present in decomposed or old specimens, only recently forensic geneticists have started to adopt those protocols. Here, we compare an ancient DNA extraction protocol (Dabney) with a bone extraction method (Loreille) typically used in forensics. Real-time quantitative PCR and forensically representative typing methods including fragment size analysis and sequencing were used to assess protocol performance. We used four bone samples of different age in replicates to study the effects of both extraction methods. Our results confirm Loreille’s overall increased gain of DNA when enough tissue is available and Dabney’s improved efficiency for retrieving shorter DNA fragments that is beneficial when highly degraded DNA is present. The results suggest that the choice of extraction method needs to be based on available sample, degradation state, and targeted genotyping method. We modified the Dabney protocol by pooling parallel lysates prior to purification to study gain and performance in single tube typing assays and found that up to six parallel lysates lead to an almost linear gain of extracted DNA. These data are promising for further forensic investigations as the adapted Dabney protocol combines increased sensitivity for degraded DNA with necessary total DNA amount for forensic applications.
Geoarchaeology: A Review of Case Studies in the Mediterranean Sea
Authors: Amato Vincenzo
Published: January 2021

The term “geoarchaeology” was established within the last 50 years, although earlier applications of this field can be found [...]