bluuebunny/crossref_metadata_2025 huggingface dataset:
An Overview on Atomization and Its Drug Delivery and Biomedical Applications
Authors: Mohandas Anu , Luo Hongrong , Ramakrishna Seeram
Published: June 2021

Atomization is an intricate operation involving unstable and complex networks with rupture and fusion of liquid molecules. There are diverse details that typify the spray formation, which are the technique and configuration of the atomization process, dimension and structure of the nozzle, experimental parameters, etc. Ultimately, the process generates fine sprays from the bulk of a liquid. Some examples of atomization that we come across in our day-to-day life are antiperspirant or hair spray, shower head, garden sprinkler, or cologne mist. In this review paper we are briefly discussing the theoretical steps taking place in an atomization technique. The instabilities of the jet and sheet are explained to understand the underlying theory that breaks the jet or sheet into droplets. Different types of atomization processes based on the energy sources are also summarized to give an idea about the advantages and disadvantages of these techniques. We are also discussing the various biomedical applications of the electrohydrodynamic atomization and its potential to use as a drug delivery system. In short, this paper is trying to demonstrate the diverse applications of atomization to show its potency as a user friendly and cost-effective technique for various purposes.
A Binocular Vision-Based 3D Sampling Moiré Method for Complex Shape Measurement
Authors: Shi Wenxiong , Zhang Qi , Xie Huimin , He Wei
Published: June 2021

As a promising method for moiré processing, sampling moiré has attracted significant interest for binocular vision-based 3D measurement, which is widely used in many fields of science and engineering. However, one key problem of its 3D shape measurement is that the visual angle difference between the left and right cameras causes inconsistency of the fringe image carrier fields, resulting in the phase mismatch of sampling moiré. In this paper, we developed a phase correction method to solve this problem. After epipolar rectification and carrier phase introduction and correction, the absolute phase of the fringe images was obtained. A more universal 3D sampling moiré measurement can be achieved based on the phase match and binocular vision model. Our numerical simulation and experiment showed the high robustness and anti-noise ability of this new 3D sampling moiré method for high-precision 3D shape measurement. As an application, cantilever beams are fabricated by directed energy deposition (DED) using different process parameters, and their 3D deformation caused by residual stresses is measured, showing great potential for residual stress analyses during additive manufacturing.
Numerical Study of the Influence of the Inlet Turbulence Length Scale on the Turbulent Boundary Layer
Authors: Lee Young-Tae , Gutti Lokesh Kalyan , Lim Hee-Chang
Published: June 2021

In the past half century, large eddy simulations (LESs) have played an important role in turbulent flow simulation and improving the performance of computing technology. To generate a fully developed turbulent boundary layer in the channel domain using LES, suitable inflow conditions along with turbulent characteristics are required. This study aimed to clarify the effect of the integral length scale on the generation of turbulent boundary layers. To accomplish this, an artificially created boundary layer was imposed on the inlet section, which gradually evolved into a fully developed turbulent boundary layer flow inside the numerical domain. In this study, the synthetic inflow method, which is a commonly employed technique, was used by imposing the spatial and temporal correlation between two different points on the inlet section. In addition, we conducted parametric length scale studies on the inlet section and compared our results with existing data. The results showed that the larger length scales in the spanwise direction were not only effective in achieving the target shape of a fully developed turbulent boundary layer, but also developed it faster than the smaller length scales.
Dysphagia-Related Health Information Improved Consumer Acceptability of Thickened Beverages
Authors: An Ji-Hye , Yoon Jin-A , Shin Myung-Jun , Kim Sang-Hun , Lee Jee-Hyun
Published: June 2021

Most people tend to think that healthy foods do not taste good. This view could have a negative impact on the taste of the food that people eat for health. However, if health-related information is provided to avoid negative aspects, acceptability may improve. Thus, this study investigated changes in consumers’ sensory perception of thickened beverages before and after the provision of dysphagia-related health information. Sixty young (19–39 years old) and middle-aged (40–64 years old) consumers participated in two experiment sessions conducted one week apart. The first session proceeded without any information and the second provided information about dysphagia and the need for dietary modification before evaluation. Three beverages (orange juice, red bean water, and sports drink) were used in nectar-like (51–350 cP) and honey-like (351–1750 cP) forms; original beverage samples (0%) were used as the control. Consumers were asked about acceptability, liking the flavor, intensity, and general health interest (GHI). An analysis of variance was performed to show the change in flavor rating and acceptability between the two sessions. Although there were age-related differences in response to the samples, thickened beverages were rated as more acceptable, in terms of their characteristics (swallowing, viscosity, and mouthfeel) after the information was provided. There were no significant differences for the 0% samples. The mean GHI values were 3.97 ± 0.85 and 4.81 ± 0.68 for the young and middle-aged groups, respectively. High and low GHI groups were analyzed. The high GHI group showed significant differences in acceptability in the informed evaluation, whereas the low GHI group was not influenced by the information.
Growth Optimisation and Kinetic Profiling of Diesel Biodegradation by a Cold-Adapted Microbial Consortium Isolated from Trinity Peninsula, Antarctica
Authors: Roslee Ahmad Fareez Ahmad , Gomez-Fuentes Claudio , Zakaria Nur Nadhirah , Shaharuddin Nor Azmi , Zulkharnain Azham , Abdul Khalil Khalilah , Convey Peter , Ahmad Siti Aqlima
Published: June 2021

Pollution associated with petrogenic hydrocarbons is increasing in Antarctica due to a combination of increasing human activity and the continent’s unforgiving environmental conditions. The current study focuses on the ability of a cold-adapted crude microbial consortium (BS24), isolated from soil on the north-west Antarctic Peninsula, to metabolise diesel fuel as the sole carbon source in a shake-flask setting. Factors expected to influence the efficiency of diesel biodegradation, namely temperature, initial diesel concentration, nitrogen source type and concentration, salinity and pH were studied. Consortium BS24 displayed optimal cell growth and diesel degradation activity at 1.0% NaCl, pH 7.5, 0.5 g/L NH4Cl and 2.0% v/v initial diesel concentration during one-factor-at-a-time (OFAT) analyses. The consortium was psychrotolerant based on the optimum growth temperature of 10‒15 °C. In conventionally optimised media, the highest total petroleum hydrocarbons (TPH) mineralisation was 85% over a 7-day incubation. Further optimisation of conditions predicted through statistical response-surface methodology (RSM) (1.0% NaCl, pH 7.25, 0.75 g/L NH4Cl, 12.5 °C and 1.75% v/v initial diesel concentration) boosted mineralisation to 95% over a 7-day incubation. A Tessier secondary model best described the growth pattern of BS24 in diesel-enriched medium, with maximum specific growth rate, μmax, substrate inhibition constant, Ki and half saturation constant, Ks, being 0.9996 h−1, 1.356% v/v and 1.238% v/v, respectively. The data obtained suggest the potential of microbial consortia such as BS24 in bioremediation applications in low-temperature diesel-polluted soils.
Friends or Foes—Microbial Interactions in Nature
Authors: Weiland-Bräuer Nancy
Published: June 2021

Microorganisms are present in nearly every niche on Earth and mainly do not exist solely but form communities of single or mixed species. Within such microbial populations and between the microbes and a eukaryotic host, various microbial interactions take place in an ever-changing environment. Those microbial interactions are crucial for a successful establishment and maintenance of a microbial population. The basic unit of interaction is the gene expression of each organism in this community in response to biotic or abiotic stimuli. Differential gene expression is responsible for producing exchangeable molecules involved in the interactions, ultimately leading to community behavior. Cooperative and competitive interactions within bacterial communities and between the associated bacteria and the host are the focus of this review, emphasizing microbial cell–cell communication (quorum sensing). Further, metagenomics is discussed as a helpful tool to analyze the complex genomic information of microbial communities and the functional role of different microbes within a community and to identify novel biomolecules for biotechnological applications.
Endometrial Carcinoma: Immune Microenvironment and Emerging Treatments in Immuno-Oncology
Authors: Rousset-Rouviere Sandrine , Rochigneux Philippe , Chrétien Anne-Sophie , Fattori Stéphane , Gorvel Laurent , Provansal Magali , Lambaudie Eric , Olive Daniel , Sabatier Renaud
Published: June 2021

Endometrial cancer (EC) can easily be cured when diagnosed at an early stage. However, advanced and metastatic EC is a common disease, affecting more than 15,000 patients per year in the United Sates. Only limited treatment options were available until recently, with a taxane–platinum combination as the gold standard in first-line setting and no efficient second-line chemotherapy or hormone therapy. EC can be split into four molecular subtypes, including hypermutated cases with POLE mutations and 25–30% harboring a microsatellite instability (MSI) phenotype with mismatch repair deficiency (dMMR). These tumors display a high load of frameshift mutations, leading to increased expression of neoantigens that can be targeted by the immune system, including (but not limited) to T-cell response. Recent data have demonstrated this impact of programmed death 1 and programmed death ligand 1 (PD-1/PD-L1) inhibitors on chemo-resistant metastatic EC. The uncontrolled KEYNOTE-158 and GARNET trials have shown high response rates with pembrolizumab and dostarlimab in chemoresistant MSI-high tumors. Most responders experiment long responses that last more than one year. Similar, encouraging results were obtained for MMR proficient (MMRp) cases treated with a combination of pembrolizumab and the angiogenesis inhibitor lenvatinib. Approvals have, thus, been obtained or are underway for EC with immune checkpoint inhibitors (ICI) used as monotherapy, and in combination with antiangiogenic agents. Combinations with other targeted therapies are under evaluation and randomized studies are ongoing to explore the impact of ICI-chemotherapy triplets in first-line setting. We summarize in this review the current knowledge of the immune environment of EC, both for MMRd and MMRp tumors. We also detail the main clinical data regarding PD-1/PD-L1 inhibitors and discuss the next steps of development for immunotherapy, including various ICI-based combinations planned to limit resistance to immunotherapy.
RABL6A Promotes Pancreatic Neuroendocrine Tumor Angiogenesis and Progression In Vivo
Authors: Maharjan Chandra K. , Umesalma Shaikamjad , Kaemmer Courtney A. , Muniz Viviane P. , Bauchle Casey , Mott Sarah L. , Zamba K. D. , Breheny Patrick , Leidinger Mariah R. , Darbro Benjamin W. , Stephens Samuel B. , Meyerholz David K. , Quelle Dawn E.
Published: June 2021

Pancreatic neuroendocrine tumors (pNETs) are difficult-to-treat neoplasms whose incidence is rising. Greater understanding of pNET pathogenesis is needed to identify new biomarkers and targets for improved therapy. RABL6A, a novel oncogenic GTPase, is highly expressed in patient pNETs and required for pNET cell proliferation and survival in vitro. Here, we investigated the role of RABL6A in pNET progression in vivo using a well-established model of the disease. RIP-Tag2 (RT2) mice develop functional pNETs (insulinomas) due to SV40 large T-antigen expression in pancreatic islet β cells. RABL6A loss in RT2 mice significantly delayed pancreatic tumor formation, reduced tumor angiogenesis and mitoses, and extended survival. Those effects correlated with upregulation of anti-angiogenic p19ARF and downregulation of proangiogenic c-Myc in RABL6A-deficient islets and tumors. Our findings demonstrate that RABL6A is a bona fide oncogenic driver of pNET angiogenesis and development in vivo.
Survival Bias and Crosstalk between Chronological and Behavioral Age: Age- and Genotype-Sensitivity Tests Define Behavioral Signatures in Middle-Aged, Old, and Long-Lived Mice with Normal and AD-Associated Aging
Authors: Giménez-Llort Lydia , Marin-Pardo Daniela , Marazuela Paula , Hernández-Guillamón Mar
Published: June 2021

New evidence refers to a high degree of heterogeneity in normal but also Alzheimer’s disease (AD) clinical and temporal patterns, increased mortality, and the need to find specific end-of-life prognosticators. This heterogeneity is scarcely explored in very old male AD mice models due to their reduced survival. In the present work, using 915 (432 APP23 and 483 C57BL/6 littermates) mice, we confirmed the better survival curves in male than female APP23 mice and respective wildtypes, providing the chance to characterize behavioral signatures in middle-aged, old, and long-lived male animals. The sensitivity of a battery of seven paradigms for comprehensive screening of motor (activity and gait analysis), neuropsychiatric and cognitive symptoms was analyzed using a cohort of 56 animals, composed of 12-, 18- and 24-month-old male APP23 mice and wildtype littermates. Most variables analyzed detected age-related differences. However, variables related to coping with stress, thigmotaxis, frailty, gait, and poor cognition better discriminated the behavioral phenotype of male APP23 mice through the three old ages compared with controls. Most importantly, non-linear age- and genotype-dependent behavioral signatures were found in long-lived animals, suggesting crosstalk between chronological and biological/behavioral ages useful to study underlying mechanisms and distinct compensations through physiological and AD-associated aging.
The Core Stem Genes SOX2, POU5F1/OCT4, and NANOG Are Expressed in Human Parathyroid Tumors and Modulated by MEN1, YAP1, and β-catenin Pathways Activation
Authors: Verdelli Chiara , Morotti Annamaria , Tavanti Giulia Stefania , Silipigni Rosamaria , Guerneri Silvana , Ferrero Stefano , Vicentini Leonardo , Vaira Valentina , Corbetta Sabrina
Published: June 2021

Tumors of the parathyroid glands are the second most common endocrine neoplasia. Epigenetic studies revealed an embryonic signature involved in parathyroid tumorigenesis. Here, we investigated the expression of the stem core genes SOX2, POU5F1/OCT4, and NANOG. Rare cells within normal parathyroid glands expressed POU5F1/OCT4 and NANOG, while SOX2 was undetectable. Nuclear SOX2 expression was detectable in 18% of parathyroid adenomas (PAds, n = 34) involving 5–30% of cells, while OCT4 and NANOG were expressed at the nuclear level in a more consistent subset of PAds involving 15–40% of cells. Most parathyroid carcinomas expressed the core stem genes. SOX2-expressing cells co-expressed parathormone (PTH). In PAds-derived primary cultures, silencing of the tumor suppressor gene MEN1 induced the expression of SOX2, likely through a MEN1/HAR1B/SOX2 axis, while calcium-sensing receptor activation increased SOX2 mRNA levels through YAP1 activation. In addition, inducing nuclear β-catenin accumulation in PAds-derived primary cultures by short-term incubation with lithium chloride (LiCl), SOX2 and POU5F1/OCT4 expression levels increased, while NANOG transcripts were reduced, and LiCl long-term incubation induced an opposite pattern of gene expression. In conclusion, detection of the core stem genes in parathyroid tumors supports their embryogenic signature, which is modulated by crucial genes involved in parathyroid tumorigenesis.
A Survey on Socially Assistive Robotics: Clinicians’ and Patients’ Perception of a Social Robot within Gait Rehabilitation Therapies
Authors: Raigoso Denniss , Céspedes Nathalia , Cifuentes Carlos A. , del-Ama Antonio J. , Múnera Marcela
Published: June 2021

A growing interest in Socially Assistive Robotics in Physical Rehabilitation is currently observed; some of the benefits highlight the capability of a social robot to support and assist rehabilitation procedures. This paper presents a perception study that aimed to evaluate clinicians’ and patients’ perception of a social robot that will be integrated as part of Lokomat therapy. A total of 88 participants were surveyed, employing an online questionnaire based on the Unified Theory of Acceptance and Use of Technology (UTAUT). The participants belong to two health care institutions located in different countries (Colombia and Spain). The results showed an overall positive perception of the social robot (>60% of participants have a positive acceptance). Furthermore, a difference depending on the nature of the user (clinician vs. patient) was found.
Health-Related Quality of Life in Very Long-Term Cancer Survivors 14–24 Years Post-Diagnosis Compared to Population Controls: A Population-Based Study
Authors: Doege Daniela , Thong Melissa S. Y. , Weißer Linda , Koch-Gallenkamp Lena , Jansen Lina , Bertram Heike , Eberle Andrea , Holleczek Bernd , Nennecke Alice , Pritzkuleit Ron , Waldmann Annika , Zeissig Sylke Ruth , Brenner Hermann , Arndt Volker
Published: June 2021

(1) Background: Little is known about the health-related quality of life (HRQoL) in very long-term cancer survivors (VLTCS) 10 and more years post-diagnosis. The objective was to compare cancer survivors’ HRQoL 14–24 years post-diagnosis with that of same-aged non-cancer controls, stratified by age, sex, and disease status (disease-free vs. stage IV, recurrence, metastasis, or second cancer). (2) Methods: We recruited 2704 very long-term survivors of breast, colorectal and prostate cancer, and 1765 controls in German multi-regional population-based studies. The HRQoL was assessed by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30). Differences in the HRQoL were estimated with multiple regression, controlling for age, sex (where appropriate), and education. (3) Results: The overall global health status/quality of life of VLTCS more than a decade after diagnosis was slightly higher than that of population controls of the same age, but more symptoms and lower functioning were reported. Differences were small but statistically significant. Results differed by age, sex, and disease status. (4) Conclusions: The findings point out the need for a comprehensive survivorship care program in order to monitor and treat potential late and long-term effects after the diagnosis and treatment of cancer. Survivorship care should be risk-adapted to survivors’ needs according to sociodemographic and clinical factors.
ECM Remodeling in Squamous Cell Carcinoma of the Aerodigestive Tract: Pathways for Cancer Dissemination and Emerging Biomarkers
Authors: Fejza Albina , Camicia Lucrezia , Poletto Evelina , Carobolante Greta , Mongiat Maurizio , Andreuzzi Eva
Published: June 2021

Squamous cell carcinomas (SCC) include a number of different types of tumors developing in the skin, in hollow organs, as well as the upper aerodigestive tract (UADT) including the head and neck region and the esophagus which will be dealt with in this review. These tumors are often refractory to current therapeutic approaches with poor patient outcome. The most important prognostic determinant of SCC tumors is the presence of distant metastasis, significantly correlating with low patient survival rates. Rapidly emerging evidence indicate that the extracellular matrix (ECM) composition and remodeling profoundly affect SSC metastatic dissemination. In this review, we will summarize the current knowledge on the role of ECM and its remodeling enzymes in affecting the growth and dissemination of UADT SCC. Taken together, these published evidence suggest that a thorough analysis of the ECM composition in the UADT SCC microenvironment may help disclosing the mechanism of resistance to the treatments and help defining possible targets for clinical intervention.
Oncolytic Viruses in Combination Therapeutic Approaches with Epigenetic Modulators: Past, Present, and Future Perspectives
Authors: Chianese Annalisa , Santella Biagio , Ambrosino Annalisa , Stelitano Debora , Rinaldi Luca , Galdiero Massimiliano , Zannella Carla , Franci Gianluigi
Published: June 2021

According to the World Cancer Report, cancer rates have been increased by 50% with 15 million new cases in the year 2020. Hepatocellular carcinoma (HCC) is the only one of the most common tumors to cause a huge increase in mortality with a survival rate between 40% and 70% at 5 years, due to the high relapse and limitations associated with current therapies. Despite great progress in medicine, oncological research is always looking for new therapies: different technologies have been evaluated in clinical trials and others have been already used in clinics. Among them, oncolytic virotherapy represents a therapeutic option with a widespread possibility of approaches and applications. Oncolytic viruses are naturally occurring, or are engineered, viruses characterized by the unique features of preferentially infecting, replicating, and lysing malignant tumor cells, as well as activating the immune response. The combination of oncolytic virotherapy and chemical drugs are arousing great interest in the tumor treatment. In this scenario, novel and promising anticancer therapies comprise combinations of oncolytic viruses and epigenetic modulators or inhibitors of the signalling pathways. Combination treatments are required to improve the immune response and allow viral entry, replication, and diffusion between proximal cells. In this review, we summarize all combination therapies associated with virotherapy, including co-administered inhibitors of chromatin modifiers (combination strategies) and inserted target sites for miRNAs (recombination or arming strategies).
A Serum Metabolomics Classifier Derived from Elderly Patients with Metastatic Colorectal Cancer Predicts Relapse in the Adjuvant Setting
Authors: Di Donato Samantha , Vignoli Alessia , Biagioni Chiara , Malorni Luca , Mori Elena , Tenori Leonardo , Calamai Vanessa , Parnofiello Annamaria , Di Pierro Giulia , Migliaccio Ilenia , Cantafio Stefano , Baraghini Maddalena , Mottino Giuseppe , Becheri Dimitri , Del Monte Francesca , Miceli Elisangela , McCartney Amelia , Di Leo Angelo , Luchinat Claudio , Biganzoli Laura
Published: June 2021

Adjuvant treatment for patients with early stage colorectal cancer (eCRC) is currently based on suboptimal risk stratification, especially for elderly patients. Metabolomics may improve the identification of patients with residual micrometastases after surgery. In this retrospective study, we hypothesized that metabolomic fingerprinting could improve risk stratification in patients with eCRC. Serum samples obtained after surgery from 94 elderly patients with eCRC (65 relapse free and 29 relapsed, after 5-years median follow up), and from 75 elderly patients with metastatic colorectal cancer (mCRC) obtained before a new line of chemotherapy, were retrospectively analyzed via proton nuclear magnetic resonance spectroscopy. The prognostic role of metabolomics in patients with eCRC was assessed using Kaplan–Meier curves. PCA-CA-kNN could discriminate the metabolomic fingerprint of patients with relapse-free eCRC and mCRC (70.0% accuracy using NOESY spectra). This model was used to classify the samples of patients with relapsed eCRC: 69% of eCRC patients with relapse were predicted as metastatic. The metabolomic classification was strongly associated with prognosis (p-value 0.0005, HR 3.64), independently of tumor stage. In conclusion, metabolomics could be an innovative tool to refine risk stratification in elderly patients with eCRC. Based on these results, a prospective trial aimed at improving risk stratification by metabolomic fingerprinting (LIBIMET) is ongoing.
HGF/c-Met Inhibition as Adjuvant Therapy Improves Outcomes in an Orthotopic Mouse Model of Pancreatic Cancer
Authors: Pang Tony C. Y. , Xu Zhihong , Mekapogu Alpha Raj , Pothula Srinivasa , Becker Therese , Corley Susan , Wilkins Marc R. , Goldstein David , Pirola Romano , Wilson Jeremy , Apte Minoti
Published: June 2021

Background: Inhibition of hepatocyte growth factor (HGF)/c-MET pathway, a major mediator of pancreatic stellate cell (PSC)−PC cell interactions, retards local and distant cancer progression. This study examines the use of this treatment in preventing PC progression after resection. We further investigate the postulated existence of circulating PSCs (cPSCs) as a mediator of metastatic PC. Methods: Two orthotopic PC mouse models, produced by implantation of a mixture of luciferase-tagged human pancreatic cancer cells (AsPC-1), and human PSCs were used. Model 1 mice underwent distal pancreatectomy 3-weeks post-implantation (n = 62). One-week post-resection, mice were randomised to four treatments of 8 weeks: (i) IgG, (ii) gemcitabine (G), (iii) HGF/c-MET inhibition (HiCi) and (iv) HiCi + G. Tumour burden was assessed longitudinally by bioluminescence. Circulating tumour cells and cPSCs were enriched by filtration. Tumours of Model 2 mice progressed for 8 weeks prior to the collection of primary tumour, metastases and blood for single-cell RNA-sequencing (scRNA-seq). Results: HiCi treatments: (1) reduced both the risk and rate of disease progression after resection; (2) demonstrated an anti-angiogenic effect on immunohistochemistry; (3) reduced cPSC counts. cPSCs were identified using immunocytochemistry (α-smooth muscle actin+, pan-cytokeratin−, CD45−), and by specific PSC markers. scRNA-seq confirmed the existence of cPSCs and identified potential genes associated with development into cPSCs. Conclusions: This study is the first to demonstrate the efficacy of adjuvant HGF/c-Met inhibition for PC and provides the first confirmation of the existence of circulating PSCs.
Glycemic Control for Colorectal Cancer Survivors Compared to Those without Cancer in the Dutch Primary Care for Type 2 Diabetes: A Prospective Cohort Study
Authors: de Haan-Du Jing , Landman Gijs W. D. , Kleefstra Nanne , Schrijnders Dennis , Manders Marjolijn , Bos Amanda C. R. K. , Tromp-van Driel Cathrien , Denig Petra , Groenier Klaas H. , de Bock Geertruida H.
Published: June 2021

Cancer survivors with diabetes tend to have worse glycemic control after their cancer diagnosis, which may increase the risk of cardiovascular diseases. We aimed to investigate whether glycemic control differs between colorectal cancer (CRC) survivors and those without cancer, among patients with type 2 diabetes being treated in the Dutch primary care. The Zwolle Outpatient Diabetes project Integrating Available Care database was linked with the Dutch Cancer Registry (n = 71,648, 1998–2014). The cases were those with stage 0–III CRC, and the controls were those without cancer history. The primary and secondary outcomes were the probability of reaching the glycated hemoglobin (HbA1c) target and the mean of HbA1c during follow-up, respectively. Mixed linear modeling was applied, where the status of CRC was a time-varying variable. Among the 57,330 patients included, 705 developed CRC during follow-up. The mean probability of reaching the HbA1c target during follow-up was 73% versus 74% (p = 0.157) for CRC survivors versus those without cancer, respectively. The mean HbA1c was 51.1 versus 50.8 mmol/mol (p = 0.045) among CRC survivors versus those without cancer, respectively. We observed a clinically comparable glycemic control among the CRC survivors without cancer, indicating that glycemic control for CRC survivors can be delegated to primary care professionals.
Astrocyte Networks as Therapeutic Targets in Glaucomatous Neurodegeneration
Authors: Boal Andrew M. , Risner Michael L. , Cooper Melissa L. , Wareham Lauren K. , Calkins David J.
Published: June 2021

Astrocytes are intimately involved in the response to neurodegenerative stress and have become an attractive target for the development of neuroprotective therapies. However, studies often focus on astrocytes as single-cell units. Astrocytes are densely interconnected by gap junctions that are composed primarily of the protein connexin-43 (Cx43) and can function as a broader network of cells. Such networks contribute to a number of important processes, including metabolite distribution and extracellular ionic buffering, and are likely to play an important role in the progression of neurodegenerative disease. This review will focus on the pro-degenerative and pro-survival influence of astrocyte Cx43 in disease progression, with a focus on the roles of gap junctions and hemichannels in the spread of degenerative stress. Finally, we will highlight the specific evidence for targeting these networks in the treatment of glaucomatous neurodegeneration and other optic neuropathies.
Adaptive Subsets Limit the Anti-Tumoral NK-Cell Activity in Hepatocellular Carcinoma
Authors: Rennert Charlotte , Tauber Catrin , Fehrenbach Pia , Heim Kathrin , Bettinger Dominik , Sogukpinar Özlem , Schuch Anita , Zecher Britta Franziska , Bengsch Bertram , Lang Sven A. , Bronsert Peter , Björkström Niklas K. , Fichtner-Feigl Stefan , Schultheiss Michael , Thimme Robert , Hofmann Maike
Published: June 2021

Hepatocellular carcinoma (HCC) is a global health burden with increasing incidence, poor prognosis and limited therapeutic options. Natural killer (NK) cells exhibit potent anti-tumoral activity and therefore represent potential targets for immunotherapeutic approaches in HCC treatment. However, the anti-tumoral activity of NK cells in HCC associated with different etiologies, and the impact of the heterogeneous NK cell subset, e.g., adaptive and conventional subsets, are not understood in detail. By comparatively analyzing the NK-cell repertoire in 60 HCC patients, 33 liver cirrhosis patients and 36 healthy donors (HD), we show in this study that the NK-cell repertoire is linked to HCC etiology, with increased frequencies of adaptive NK cells in Hepatitis B virus (HBV)-associated HCC. Adaptive NK cells exhibited limited anti-tumoral activity toward liver cancer cells; however, this was not a result of a specific NK-cell impairment in HCC but rather represented an intrinsic feature, since the characteristics of circulating and intra-tumoral adaptive NK cells were conserved between HD, HCC and liver cirrhosis patients. Hence, the expansion of adaptive NK cells with reduced anti-tumoral activity, detectable in HBV-associated HCC, may have implications for tumor surveillance and therapy.
An Insight into the microRNAs Associated with Arteriovenous and Cavernous Malformations of the Brain
Authors: Florian Ioan Alexandru , Buruiana Andrei , Timis Teodora Larisa , Susman Sergiu , Florian Ioan Stefan , Balasa Adrian , Berindan-Neagoe Ioana
Published: June 2021

Background: Brain arteriovenous malformations (BAVMs) and cerebral cavernous malformations (CCMs) are rare developmental anomalies of the intracranial vasculature, with an irregular tendency to rupture, and as of yet incompletely deciphered pathophysiology. Because of their variety in location, morphology, and size, as well as unpredictable natural history, they represent a management challenge. MicroRNAs (miRNAs) are strands of non-coding RNA of around 20 nucleotides that are able to modulate the expression of target genes by binding completely or partially to their respective complementary sequences. Recent breakthroughs have been made on elucidating their contribution to BAVM and CCM occurrence, growth, and evolution; however, there are still countless gaps in our understanding of the mechanisms involved. Methods: We have searched the Medline (PubMed; PubMed Central) database for pertinent articles on miRNAs and their putative implications in BAVMs and CCMs. To this purpose, we employed various permutations of the terms and idioms: ‘arteriovenous malformation’, ‘AVM’, and ‘BAVM’, or ‘cavernous malformation’, ‘cavernoma’, and ‘cavernous angioma’ on the one hand; and ‘microRNA’, ‘miRNA’, and ‘miR’ on the other. Using cross-reference search; we then investigated additional articles concerning the individual miRNAs identified in other cerebral diseases. Results: Seven miRNAs were discovered to play a role in BAVMs, three of which were downregulated (miR-18a, miR-137, and miR-195*) and four upregulated (miR-7-5p, miR-199a-5p, miR-200b-3p, and let-7b-3p). Similarly, eight miRNAs were identified in CCM in humans and experimental animal models, two being upregulated (miR-27a and mmu-miR-3472a), and six downregulated (miR-125a, miR-361-5p, miR-370-3p, miR-181a-2-3p, miR-95-3p, and let-7b-3p). Conclusions: The following literature review endeavored to address the recent discoveries related to the various implications of miRNAs in the formation and growth of BAVMs and CCMs. Additionally, by presenting other cerebral pathologies correlated with these miRNAs, it aimed to emphasize the potential directions of upcoming research and biological therapies.
Toll-Like Receptor Signaling in the Establishment and Function of the Immune System
Authors: Aluri Jahnavi , Cooper Megan A. , Schuettpelz Laura G.
Published: June 2021

Toll-like receptors (TLRs) are pattern recognition receptors that play a central role in the development and function of the immune system. TLR signaling promotes the earliest emergence of hematopoietic cells during development, and thereafter influences the fate and function of both primitive and effector immune cell types. Aberrant TLR signaling is associated with hematopoietic and immune system dysfunction, and both loss- and gain-of- function variants in TLR signaling-associated genes have been linked to specific infection susceptibilities and immune defects. Herein, we will review the role of TLR signaling in immune system development and the growing number of heritable defects in TLR signaling that lead to inborn errors of immunity.
A Review of Heavy-Duty Vehicle Powertrain Technologies: Diesel Engine Vehicles, Battery Electric Vehicles, and Hydrogen Fuel Cell Electric Vehicles
Authors: Cunanan Carlo , Tran Manh-Kien , Lee Youngwoo , Kwok Shinghei , Leung Vincent , Fowler Michael
Published: June 2021

Greenhouse gas emissions from the freight transportation sector are a significant contributor to climate change, pollution, and negative health impacts because of the common use of heavy-duty diesel vehicles (HDVs). Governments around the world are working to transition away from diesel HDVs and to electric HDVs, to reduce emissions. Battery electric HDVs and hydrogen fuel cell HDVs are two available alternatives to diesel engines. Each diesel engine HDV, battery-electric HDV, and hydrogen fuel cell HDV powertrain has its own advantages and disadvantages. This work provides a comprehensive review to examine the working mechanism, performance metrics, and recent developments of the aforementioned HDV powertrain technologies. A detailed comparison between the three powertrain technologies, highlighting the advantages and disadvantages of each, is also presented, along with future perspectives of the HDV sector. Overall, diesel engine in HDVs will remain an important technology in the short-term future due to the existing infrastructure and lower costs, despite their high emissions, while battery-electric HDV technology and hydrogen fuel cell HDV technology will be slowly developed to eliminate their barriers, including costs, infrastructure, and performance limitations, to penetrate the HDV market.
Carbon Capture from Biogas by Deep Eutectic Solvents: A COSMO Study to Evaluate the Effect of Impurities on Solubility and Selectivity
Authors: Quaid Thomas , Reza M. Toufiq
Published: June 2021

Deep eutectic solvents (DES) are compounds of a hydrogen bond donor (HBD) and a hydrogen bond acceptor (HBA) that contain a depressed melting point compared to their individual constituents. DES have been studied for their use as carbon capture media and biogas upgrading. However, contaminants’ presence in biogas might affect the carbon capture by DES. In this study, conductor-like screening model for real solvents (COSMO-RS) was used to determine the effect of temperature, pressure, and selective contaminants on five DES’ namely, choline chloride-urea, choline chloride-ethylene glycol, tetra butyl ammonium chloride-ethylene glycol, tetra butyl ammonium bromide-decanoic acid, and tetra octyl ammonium chloride-decanoic acid. Impurities studied in this paper are hydrogen sulfide, ammonia, water, nitrogen, octamethyltrisiloxane, and decamethylcyclopentasiloxane. At infinite dilution, CO2 solubility dependence upon temperature in each DES was examined by means of Henry’s Law constants. Next, the systems were modeled from infinite dilution to equilibrium using the modified Raoults’ Law, where CO2 solubility dependence upon pressure was examined. Finally, solubility of CO2 and CH4 in the various DES were explored with the presence of varying mole percent of selective contaminants. Among the parameters studied, it was found that the HBD of the solvent is the most determinant factor for the effectiveness of CO2 solubility. Other factors affecting the solubility are alkyl chain length of the HBA, the associated halogen, and the resulting polarity of the DES. It was also found that choline chloride-urea is the most selective to CO2, but has the lowest CO2 solubility, and is the most polar among other solvents. On the other hand, tetraoctylammonium chloride-decanoic acid is the least selective, has the highest maximum CO2 solubility, is the least polar, and is the least affected by its environment.
Association of the IL-37 Polymorphisms with Transaminases and Alkaline Phosphatase Levels in Premature Coronary Artery Disease Patients and Healthy Controls. Results of the Genetics of Atherosclerotic (GEA) Mexican Study
Authors: López-Bautista Fabiola , Posadas-Sánchez Rosalinda , Vargas-Alarcón Gilberto
Published: June 2021

Interleukin 37 (IL-37) is an anti-inflammatory cytokine expressed in foam cells located in the atherosclerosis plaques. The present study aimed to evaluate the association of the IL-37 polymorphisms with premature coronary artery disease (pCAD), cardiovascular risk factors, metabolic parameters, and levels of liver enzymes. Three IL-37 polymorphisms (rs6717710, rs2708961, and rs2708947) were determined in 1161 patients with pCAD and 951 healthy controls. IL-37 polymorphisms were not associated with the presence of pCAD. The association of the polymorphisms with cardiovascular risk factors, metabolic parameters, and levels of liver enzymes was evaluated independently in pCAD and healthy controls. In pCAD patients, under different models, the rs6717710 was associated with low risk of having elevated alkaline phosphatase (ALP) (padditive = 0.020; pdominant = 0.02; pheterozygous = 0.04; pcodominant1 = 0.040). On the other hand, in healthy controls, the rs6717710 was associated with low risk of having elevated levels of alanine aminotransferase (ALT) (padditive = 0.04, precessive = 0.01, pcodominant2 = 0.01) and aspartate aminotransferase (AST) (padditive = 0.02, pdominant = 0.02). The IL-37 polymorphisms were not associated with the risk of pCAD. In pCAD patients, the rs6717710 was associated with low risk of having elevated ALP levels, whereas in controls was associated with low risk of having elevated ALT and AST levels.
Clinical Evaluation of the Torq Zero Delay Centrifuge System for Decentralized Blood Collection and Stabilization
Authors: Hong Kyungjin , Iacovetti Gabriella , Rahimian Ali , Hong Sean , Epperson Jon , Neal Clara , Pan Tifany , Le Angela , Kendall Eric , Melton Kory , Sommer Greg J. , Schaff Ulrich Y.
Published: June 2021

Blood sample collection and rapid separation—critical preanalytical steps in clinical chemistry—can be challenging in decentralized collection settings. To address this gap, the Torq™ zero delay centrifuge system includes a lightweight, hand-portable centrifuge (ZDrive™) and a disc-shaped blood collection device (ZDisc™) enabling immediate sample centrifugation at the point of collection. Here, we report results from clinical validation studies comparing performance of the Torq System with a conventional plasma separation tube (PST). Blood specimens from 134 subjects were collected and processed across three independent sites to compare ZDisc and PST performance in the assessment of 14 analytes (K, Na, Cl, Ca, BUN, creatinine, AST, ALT, ALP, total bilirubin, albumin, total protein, cholesterol, and triglycerides). A 31-subject precision study was performed to evaluate reproducibility of plasma test results from ZDiscs, and plasma quality was assessed by measuring hemolysis and blood cells from 10 subject specimens. The ZDisc successfully collected and processed samples from 134 subjects. ZDisc results agreed with reference PSTs for all 14 analytes with mean % biases well below clinically significant levels. Results were reproducible across different operators and ZDisc production lots, and plasma blood cell counts and hemolysis levels fell well below clinical acceptance thresholds. ZDiscs produce plasma samples equivalent to reference PSTs. Results support the suitability of the Torq System for remotely collecting and processing blood samples in decentralized settings.
Two Chebyshev Spectral Methods for Solving Normal Modes in Atmospheric Acoustics
Authors: Wang Yongxian , Tu Houwang , Liu Wei , Xiao Wenbin , Lan Qiang
Published: June 2021

The normal mode model is important in computational atmospheric acoustics. It is often used to compute the atmospheric acoustic field under a time-independent single-frequency sound source. Its solution consists of a set of discrete modes radiating into the upper atmosphere, usually related to the continuous spectrum. In this article, we present two spectral methods, the Chebyshev-Tau and Chebyshev-Collocation methods, to solve for the atmospheric acoustic normal modes, and corresponding programs are developed. The two spectral methods successfully transform the problem of searching for the modal wavenumbers in the complex plane into a simple dense matrix eigenvalue problem by projecting the governing equation onto a set of orthogonal bases, which can be easily solved through linear algebra methods. After the eigenvalues and eigenvectors are obtained, the horizontal wavenumbers and their corresponding modes can be obtained with simple processing. Numerical experiments were examined for both downwind and upwind conditions to verify the effectiveness of the methods. The running time data indicated that both spectral methods proposed in this article are faster than the Legendre-Galerkin spectral method proposed previously.
A New Overdispersed Integer-Valued Moving Average Model with Dependent Counting Series
Authors: Yu Kaizhi , Wang Huiqiao
Published: June 2021

A new integer-valued moving average model is introduced. The assumption of independent counting series in the model is relaxed to allow dependence between them, leading to the overdispersion in the model. Statistical properties were established for this new integer-valued moving average model with dependent counting series. The Yule–Walker method was applied to estimate the model parameters. The estimator’s performance was evaluated using simulations, and the overdispersion test of the INMA(1) process was applied to examine the dependence between counting series.
Productive Method as the Basis for Soft Skills Development in Engineering Foreign Language Education
Authors: Medvedeva Olesya Dmitrievna , Rubtsova Anna Vladimirovna
Published: June 2021

The modern world requires engineering specialists with excellent hard skills as well as soft skills that contribute to better communication, creativity, and self-realisation of a person. The authors discovered that modern educational standards are starting to focus on soft skills development, proposing requirements for educational programs that contain competencies covering soft skills. To fulfil such needs, there is the productive method of foreign language teaching that implies interactive technologies and masters foreign language communicative competence and soft skills at once. Therefore, the study aimed at developing a technology of soft skills development in engineering foreign language education using the productive method and checking its effectiveness. The authors designed a questionnaire and investigated engineering students’ opinions on a need to develop soft skills, which revealed high relevance of the topic, and the possibility of their development while studying a foreign language, which proved the productive method’s prospects. Based on findings received and literature analysed, we implemented case studies, problem-based learning, and essay writing in the technology and designed assessment criteria. Testing of the technology was performed by a pedagogical experiment, where qualitative and quantitative methods were applied. To critically analyse the results, we used Cronbach’s alpha, which revealed good reliability of the questionnaire, and t-test showed high efficiency of the technology that improved students’ soft skills.
Home Scholarly Culture, Book Selection Reason, and Academic Performance: Pathways to Book Reading Interest among Secondary School Students
Authors: Vuong Quan-Hoang , Nguyen Minh-Hoang , Le Tam-Tri
Published: June 2021

Although studies have explored the predictors of book reading interest among children, little is known about the underlying mechanism that helps children become interested in reading books. This study attempt to demonstrate: (1) how book-reading interest is driven by reasons for choosing books (recommendation or personal preference), (2) how students with high and low academic achievements are motivated by different thinking pathways, and (3) how home scholarly culture improves book-reading interest through such pathways. Using Bayesian analysis on a dataset of survey responses from 4966 Vietnamese secondary students (11–15 years old, sixth to ninth grade), we found: (i) Reading interest is positively associated with a book recommendation and parental book reading activities (parents read books to children); (ii) High-achieving students are more interested in reading books if they can choose those books according to personal preferences; (iii) Parental book reading activities can promote book reading interest through recommendations and also by understanding children’s personal preferences. We advocate a more personalized approach in educational policymaking, curriculum design, and home scholarly culture based on students’ abilities and perceptions.