bluuebunny/crossref_metadata_2025 huggingface dataset:
Recapitulating the Angiogenic Switch in a Hydrogel-Based 3D In Vitro Tumor-Stroma Model
Authors: Kuehlbach Claudia , Hensler Sabine , Mueller Margareta M.
Published: November 2021

To ensure nutrient and oxygen supply, tumors beyond a size of 1–2 mm3 need a connection to the vascular system. Thus, tumor cells modify physiological tissue homeostasis by secreting inflammatory and angiogenic cytokines. This leads to the activation of the tumor microenvironment and the turning of the angiogenic switch, resulting in tumor vascularization and growth. To inhibit tumor growth by developing efficient anti-angiogenic therapies, an in depth understanding of the molecular mechanism initiating angiogenesis is essential. Yet so far, predominantly 2D cell cultures or animal models have been used to clarify the interactions within the tumor stroma, resulting in poor transferability of the data obtained to the in vivo situation. Consequently, there is an abundant need for complex, humanized, 3D models in vitro. We established a dextran-hydrogel-based 3D organotypic in vitro model containing microtumor spheroids, macrophages, neutrophils, fibroblasts and endothelial cells, allowing for the analysis of tumor–stroma interactions in a controlled and modifiable environment. During the cultivation period of 21 days, the microtumor spheroids in the model grew in size and endothelial cells formed elongated tubular structures resembling capillary vessels, that appeared to extend towards the tumor spheroids. The tubular structures exhibited complex bifurcations and expanded without adding external angiogenic factors such as VEGF to the culture. To allow high-throughput screening of therapeutic candidates, the 3D cell culture model was successfully miniaturized to a 96-well format, while still maintaining the same level of tumor spheroid growth and vascular sprouting. The quantification of VEGF in the conditioned medium of these cultures showed a continuous increase during the cultivation period, suggesting the contribution of endogenous VEGF to the induction of the angiogenic switch and vascular sprouting. Thus, this model is highly suitable as a testing platform for novel anticancer therapeutics targeting the tumor as well as the vascular compartment.
Biochemical Response to Freezing in the Siberian Salamander Salamandrella keyserlingii
Authors: Shekhovtsov Sergei V. , Bulakhova Nina A. , Tsentalovich Yuri P. , Zelentsova Ekaterina A. , Meshcheryakova Ekaterina N. , Poluboyarova Tatiana V. , Berman Daniil I.
Published: November 2021

The Siberian salamander Salamandrella keyserlingii Dybowski, 1870 is a unique amphibian that is capable to survive long-term freezing at −55 °C. Nothing is known on the biochemical basis of this remarkable freezing tolerance, except for the fact that it uses glycerol as a low molecular weight cryoprotectant. We used 1H-NMR analysis to study quantitative changes of multiple metabolites in liver and hindlimb muscle of S. keyserlingii in response to freezing. For the majority of molecules we observed significant changes in concentrations. Glycerol content in frozen organs was as high as 2% w/w, which confirms its role as a cryoprotectant. No other putative cryoprotectants were detected. Freezing resulted in ischemia manifested as increased concentrations of glycolysis products: lactate and alanine. Unexpectedly, we detected no increase in concentrations of succinate, which accumulates under ischemia in various tetrapods. Freezing proved to be a dramatic stress with reduced adenosine phosphate pool and high levels of nucleotide degradation products (hypoxanthine, β-alanine, and β-aminoisobutyrate). There was also significant increase in the concentrations of choline and glycerophosphocholine, which may be interpreted as the degradation of biomembranes. Thus, we found that freezing results not only in macroscopical damage due to ice formation, but also to degradation of DNA and biomembranes.
De Novo Reconstruction of Transcriptome Identified Long Non-Coding RNA Regulator of Aging-Related Brown Adipose Tissue Whitening in Rabbits
Authors: Du Kun , Bai Xue , Yang Li , Shi Yu , Chen Li , Wang Haoding , Cai Mingchen , Wang Jie , Chen Shiyi , Jia Xianbo , Lai Songjia
Published: November 2021

Brown adipose tissues (BATs) convert to a “white-like” phenotype with age, which is also known as “aging-related BAT whitening (ARBW)”. Emerging evidence suggested that long non-coding RNAs (lncRNAs) were widely involved in adipose biology. Rabbit is an ideal model for studying the dynamics of ARBW. In this study, we performed histological analysis and strand-specific RNA-sequencing (ssRNA-seq) of rabbit interscapular adipose tissues (iATs). Our data indicated that the rabbit iATs underwent the ARBW from 0 days to 2 years and a total of 2281 novel lncRNAs were identified in the iATs. The classical rabbit BATs showed low lncRNA transcriptional complexity compared to white adipose tissues (WATs). A total of 631 differentially expressed lncRNAs (DELs) were identified in four stages. The signal pathways of purine metabolism, Wnt signaling pathway, peroxisome proliferator-activated receptor (PPAR) signaling pathway, cyclic guanosine monophosphate (cGMP)/cGMP-dependent protein kinase (cGMP-PKG) signaling pathway and lipid and atherosclerosis were significantly enriched by the DELs with unique expression patterns. A novel lncRNA that was highly expressed in the iATs of aged rabbits was validated to impair brown adipocyte differentiation in vitro. Our study provided a comprehensive catalog of lncRNAs involved in ARBW in rabbits, which facilitates a better understanding of adipose biology.
Siglecs as Therapeutic Targets in Cancer
Authors: Lim Jackwee , Sari-Ak Duygu , Bagga Tanaya
Published: November 2021

Hypersialylation is a common post-translational modification of protein and lipids found on cancer cell surfaces, which participate in cell-cell interactions and in the regulation of immune responses. Sialic acids are a family of nine-carbon α-keto acids found at the outermost ends of glycans attached to cell surfaces. Given their locations on cell surfaces, tumor cells aberrantly overexpress sialic acids, which are recognized by Siglec receptors found on immune cells to mediate broad immunomodulatory signaling. Enhanced sialylation exposed on cancer cell surfaces is exemplified as “self-associated molecular pattern” (SAMP), which tricks Siglec receptors found on leukocytes to greatly down-regulate immune responsiveness, leading to tumor growth. In this review, we focused on all 15 human Siglecs (including Siglec XII), many of which still remain understudied. We also highlighted strategies that disrupt the course of Siglec-sialic acid interactions, such as antibody-based therapies and sialic acid mimetics leading to tumor cell depletion. Herein, we introduced the central roles of Siglecs in mediating pro-tumor immunity and discussed strategies that target these receptors, which could benefit improved cancer immunotherapy.
The BPH/5 Mouse Model of Superimposed Preeclampsia Is Not a Model of HELLP Syndrome
Authors: Johnston Andrea N. , Batts Tifini L. , Langohr Ingeborg M. , Moeller Cambri , Liu Chin-Chi , Sones Jennifer L.
Published: November 2021

Preeclampsia (PE) is a multisystemic disease of pregnancy affecting 2–8% of women worldwide. PE-induced liver disease is a rare but important complication of pregnancy. The pathogenesis of liver dysfunction in PE is poorly understood, but is correlated with dysregulated angiogenic, inflammatory, and hypoxic events in the early phase of placental development. Because BPH/5 mice develop the maternal and fetal hallmarks of PE during pregnancy, we hypothesized that they may also share the clinicopathologic findings of the human PE-associated hemolysis elevated liver transaminases low platelets (HELLP) syndrome. Using this model, we determined that microangiopathic hemolysis, thrombocytopenia, and elevated liver enzymes do not occur in mid to late gestation. Pregnant BPH/5 mice do not develop histologic evidence of hepatic inflammation, but they do have increased microsteatosis scores at preconception and in mid to late gestation that progress to macrosteatosis in a subset of mice in late gestation. The transcriptional upregulation of TNF-α, CXCL-10, and TLR-2 occurs in mid gestation prior to the onset of macrosteatosis. The BPH/5 female mouse is not a model of HELLP syndrome, but may be a model of fatty liver disease associated with pregnancy.
Novice Female Exercisers Exhibited Different Biomechanical Loading Profiles during Full-Squat and Half-Squat Practice
Authors: Li Xin , Adrien Ntwali , Baker Julien S. , Mei Qichang , Gu Yaodong
Published: November 2021

Background: Females with different practice experience may show different body postures and movement patterns while squatting in different depths, which may lead to changes of biomechanical loadings and increase the risks of injuries. Methods: Sixteen novice female participants without squat training experience participated in this study. A 3D motion capture system was used to collect the marker trajectory and ground reaction force data during bodyweight squatting in different depths. The participants’ kinematic data and joint moment were calculated using OpenSim’s inverse kinematics and inverse dynamics algorithm. In this study, authors adapted a model especially developed for squatting and customized the knee joint with extra Degree-of-Freedom (DoF) in the coronal and horizontal plane with adduction/abduction and internal/external rotation. A paired-sample t-test was used to analyze the difference of joint range of motions (ROM) and peak moments between full-squat (F-SQ) and half-squat (H-SQ). One-Dimensional Statistical Parametric Mapping (SPM1D) is used to analyze the difference of joint angle and moment between the process of squatting F-SQ and H-SQ. Results: (1) Compared with H-SQ, F-SQ showed larger ROM in sagittal, coronal, and transverse planes (p < 0.05). (2) SPM1D found that the difference in joint angles and joint moments between F-SQ and H-SQ was mainly concentrated in the mid-stance during squatting, which suggested the difference is greatly pronounced during deeper squat. (3) Peak hip extension moment, knee extension moment, hip adduction moment, and plantar flexion moment of F-SQ were significantly higher than H-SQ (p < 0.05). (4) Difference of hip and knee extension moments and rotation moments between the F-SQ and H-SQ were exhibited during descending and ascending. Conclusions: The study found that novice women had larger range of joint motion during the F-SQ than H-SQ group, and knee valgus was observed during squatting to the deepest point. Greater joint moment was found during F-SQ and reached a peak during ascending after squatting to the deepest point. Novice women may have better movement control during H-SQ. The findings may provide implications for the selection of lower limb strength training programs, assist the scientific development of training movements, and provide reference for squat movement correction, thus reducing the risk of injury for novice women in squatting practice.
Effect of Customized Insoles on Gait in Post-Stroke Hemiparetic Individuals: A Randomized Controlled Trial
Authors: Wang Jie , Qiao Lei , Yu Long , Wang Yanmin , Taiar Redha , Zhang Ying , Fu Weijie
Published: November 2021

Background: Insoles have been widely applied to many diseases, but stroke involves complex problems and there is a paucity of research on the application of insoles in stroke patients. Aim: To evaluate the effect of customized insoles on gait in patients with hemiplegia. Design: A randomized controlled trial. Setting: Rehabilitation department of a hospital. Population: A total of 50 stroke patients were randomized into an experimental group (n = 25) or a control group (n = 25). Methods: Both groups received conventional gait training, which was conducted five times a week, every 40 min for four weeks and patients in the experimental group were required to wear customized insoles for at least 1 h per day for four weeks. The primary outcome measure was the Tinetti Gait Scale (TGS) and the secondary outcome measures were the plantar pressure test, 6-min walking test (6MWT), lower extremity Fugl–Meyer assessment (FMA-LE), Berg Balance Scale (BBS), and the modified Barthel index (MBI). Results: Compared to the control group, there were significant increases in the experimental group after four weeks (p = 0.014) and at the four week follow-up (p = 0.001) in the change in TGS, weight-bearing on the involved side (p = 0.012) or forefoot (p = 0.028) when standing, weight-bearing on the involved side (p = 0.01 6) or forefoot (p = 0.043) when walking, early stance phase (p = 0.023) and mid stance phase (p = 0.013) on the involved side, FMA-LE (p = 0.029), BBS (p = 0.005), and MBI (p = 0.009), but there were no differences in the late stance phase (p = 0.472) on the involved side when walking or in the 6MWT (p = 0.069). Conclusions: Customized insoles had great efficacy in enhancing gait performance in stroke patients.
Gut-Derived Endotoxin and Telomere Length Attrition in Adults with and without Type 2 Diabetes
Authors: Al-Daghri Nasser M. , Abdi Saba , Sabico Shaun , Alnaami Abdullah M. , Wani Kaiser A. , Ansari Mohammed G. A. , Khattak Malak Nawaz Khan , Khan Nasiruddin , Tripathi Gyanendra , Chrousos George P. , McTernan Philip G.
Published: November 2021

Premature aging, as denoted by a reduced telomere length (TL), has been observed in several chronic inflammatory diseases, such as obesity and type 2 diabetes mellitus (T2DM). However, no study to date has addressed the potential inflammatory influence of the gut-derived Gram-negative bacterial fragments lipopolysaccharide, also referred to as endotoxin, and its influence on TL in low-grade inflammatory states such as type 2 diabetes mellitus (T2DM). The current study therefore investigated the influence of endotoxin and inflammatory factors on telomere length (TL) in adults with (T2DM: n = 387) and without (non-diabetic (ND) controls: n = 417) obesity and T2DM. Anthropometric characteristics were taken, and fasted blood samples were used to measure biomarkers, TL, and endotoxin. The findings from this study highlighted across all participants that circulating endotoxin (r = −0.17, p = 0.01) was inversely associated with TL, noting that endotoxin and triglycerides predicted 18% of the variance perceived in TL (p < 0.001). Further stratification of the participants according to T2DM status and sex highlighted that endotoxin significantly predicted 19% of the variance denoted in TL among male T2DM participants (p = 0.007), where TL was notably influenced. The influence on TL was not observed to be impacted by anti-T2DM medications, statins, or anti-hypertensive therapies. Taken together, these results show that TL attrition was inversely associated with circulating endotoxin levels independent of the presence of T2DM and other cardiometabolic factors, suggesting that low-grade chronic inflammation may trigger premature biological aging. The findings further highlight the clinical relevance of mitigating the levels of circulating endotoxin (e.g., manipulation of gut microbiome) not only for the prevention of chronic diseases but also to promote healthy aging.
Impact of Chromatin Dynamics and DNA Repair on Genomic Stability and Treatment Resistance in Pediatric High-Grade Gliomas
Authors: Pinto Lia , Baidarjad Hanane , Entz-Werlé Natacha , Van Dyck Eric
Published: November 2021

Despite their low incidence, pediatric high-grade gliomas (pHGGs), including diffuse intrinsic pontine gliomas (DIPGs), are the leading cause of mortality in pediatric neuro-oncology. Recurrent, mutually exclusive mutations affecting K27 (K27M) and G34 (G34R/V) in the N-terminal tail of histones H3.3 and H3.1 act as key biological drivers of pHGGs. Notably, mutations in H3.3 are frequently associated with mutations affecting ATRX and DAXX, which encode a chaperone complex that deposits H3.3 into heterochromatic regions, including telomeres. The K27M and G34R/V mutations lead to distinct epigenetic reprogramming, telomere maintenance mechanisms, and oncogenesis scenarios, resulting in distinct subgroups of patients characterized by differences in tumor localization, clinical outcome, as well as concurrent epigenetic and genetic alterations. Contrasting with our understanding of the molecular biology of pHGGs, there has been little improvement in the treatment of pHGGs, with the current mainstays of therapy—genotoxic chemotherapy and ionizing radiation (IR)—facing the development of tumor resistance driven by complex DNA repair pathways. Chromatin and nucleosome dynamics constitute important modulators of the DNA damage response (DDR). Here, we summarize the major DNA repair pathways that contribute to resistance to current DNA damaging agent-based therapeutic strategies and describe the telomere maintenance mechanisms encountered in pHGGs. We then review the functions of H3.3 and its chaperones in chromatin dynamics and DNA repair, as well as examining the impact of their mutation/alteration on these processes. Finally, we discuss potential strategies targeting DNA repair and epigenetic mechanisms as well as telomere maintenance mechanisms, to improve the treatment of pHGGs.
A Review of High-Intensity Focused Ultrasound in Urology
Authors: Cranston David , Leslie Tom , ter Haar Gail
Published: November 2021

This review provides an introduction to high-intensity focused ultrasound (HIFU) and reviews its historical and current use in urological surgery. Current and historical literature (1927–2020), including that describing trials and review articles in the medical and ultrasonic literature, has been reviewed, using Pub Med and Cochrane search engines. HIFU is currently one of a number of treatments for prostate cancer, both as a primary treatment that can be repeated, and as a salvage treatment post-radiotherapy. HIFU is not yet sufficiently mature to be a standard treatment for renal cancer or other urological diseases, although there has been some success in early clinical trials. As the technology improves, this situation is likely to change. HIFU has been understood as a concept for a century, and has been applied in experimental use for half that time. It is now an accepted treatment with low morbidity in many diseases outside the scope of this review. In urological surgery, prostate HIFU is accepted as a localised treatment in selected cases, with potentially fewer side effects than other localised therapies. Currently the treatment for renal cancer is hindered by the perinephric fat and the position of the kidneys behind the ribs; however, as the technology improves with image fusion, faster treatments, and the ability with phased array transducers and motion compensation to overcome the problems caused by the ribs and breathing, successful treatment of kidney tumours will become more of a reality. In due course, there will be a new generation of machines for treating prostate cancer. These devices will further minimise the side effects of radical treatment of prostate cancer.
Kaposi’s Sarcoma in Virally Suppressed People Living with HIV: An Emerging Condition
Authors: Palich Romain , Makinson Alain , Veyri Marianne , Guihot Amélie , Valantin Marc-Antoine , Brégigeon-Ronot Sylvie , Poizot-Martin Isabelle , Solas Caroline , Grabar Sophie , Martin-Blondel Guillaume , Spano Jean-Philippe
Published: November 2021

Since the advent of highly effective combined antiretroviral treatment (cART), and with the implementation of large HIV testing programs and universal access to cART, the burden of AIDS-related comorbidities has dramatically decreased over time. The incidence of Kaposi’s sarcoma (SK), strongly associated with HIV replication and CD4 immunosuppression, was greatly reduced. However, KS remains the most common cancer in patients living with HIV (PLHIV). HIV physicians are increasingly faced with KS in virally suppressed HIV-patients, as reflected by increasing description of case series. Though SK seem less aggressive than those in PLHIV with uncontrolled HIV-disease, some may require systemic chemotherapy. Persistent lack of specific anti-HHV-8 cellular immunity could be involved in the physiopathology of these KS. These clinical forms are a real therapeutic challenge without possible short-term improvement of anti-HHV-8 immunity, and no active replication of HIV to control. The cumulative toxicity of chemotherapies repeatedly leads to a therapeutic dead end. The introduction or maintenance of protease inhibitors in cART does not seem to have an impact on the evolution of these KS. Research programs in this emerging condition are important to consider new strategies.
Identification of Cellular Factors Required for SARS-CoV-2 Replication
Authors: Synowiec Aleksandra , Jedrysik Malwina , Branicki Wojciech , Klajmon Adrianna , Lei Jing , Owczarek Katarzyna , Suo Chen , Szczepanski Artur , Wang Jingru , Zhang Pengyan , Labaj Pawel P. , Pyrc Krzysztof
Published: November 2021

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the recently emerged virus responsible for the COVID-19 pandemic. Clinical presentation can range from asymptomatic disease and mild respiratory tract infection to severe disease with lung injury, multiorgan failure, and death. SARS-CoV-2 is the third animal coronavirus to emerge in humans in the 21st century, and coronaviruses appear to possess a unique ability to cross borders between species and infect a wide range of organisms. This is somewhat surprising as, except for the requirement of host cell receptors, cell–pathogen interactions are usually species-specific. Insights into these host–virus interactions will provide a deeper understanding of the process of SARS-CoV-2 infection and provide a means for the design and development of antiviral agents. In this study, we describe a complex analysis of SARS-CoV-2 infection using a genome-wide CRISPR-Cas9 knock-out system in HeLa cells overexpressing entry receptor angiotensin-converting enzyme 2 (ACE2). This platform allows for the identification of factors required for viral replication. This study was designed to include a high number of replicates (48 replicates; 16 biological repeats with 3 technical replicates each) to prevent data instability, remove sources of bias, and allow multifactorial bioinformatic analyses in order to study the resulting interaction network. The results obtained provide an interesting insight into the replication mechanisms of SARS-CoV-2.
Local and Systemic Cytokine, Chemokine, and FGF Profile in Bacterial Chondronecrosis with Osteomyelitis (BCO)-Affected Broilers
Authors: Ramser Alison , Greene Elizabeth , Wideman Robert , Dridi Sami
Published: November 2021

Complex disease states, like bacterial chondronecrosis with osteomyelitis (BCO), not only result in physiological symptoms, such as lameness, but also a complex systemic reaction involving immune and growth factor responses. For the modern broiler (meat-type) chickens, BCO is an animal welfare, production, and economic concern involving bacterial infection, inflammation, and bone attrition with a poorly defined etiology. It is, therefore, critical to define the key inflammatory and bone-related factors involved in BCO. In this study, the local bone and systemic blood profile of inflammatory modulators, cytokines, and chemokines was elucidated along with inflammasome and key FGF genes. BCO-affected bone showed increased expression of cytokines IL-1β, while BCO-affected blood expressed upregulated TNFα and IL-12. The chemokine profile revealed increased IL-8 expression in both BCO-affected bone and blood in addition to inflammasome NLRC5 being upregulated in circulation. The key FGF receptor, FGFR1, was significantly downregulated in BCO-affected bone. The exposure of two different bone cell types, hFOB and chicken primary chondrocytes, to plasma from BCO-affected birds, as well as recombinant TNFα, resulted in significantly decreased cell viability. These results demonstrate an expression of proinflammatory and bone-resorptive factors and their potential contribution to BCO etiology through their impact on bone cell viability. This unique profile could be used for improved non-invasive detection of BCO and provides potential targets for treatments.
The Risk of Nonsteroidal Anti-Inflammatory Drugs in Pediatric Medicine: Listen Carefully to Children with Pain
Authors: Mboma Olivier , Wirth Stefan , Aydin Malik
Published: November 2021

Over the last decades, the use of over-the-counter analgesics in the general population has increased in Germany. Ibuprofen is one of the most commonly used nonsteroidal anti-inflammatory drug (NSAID) and is frequently prescribed to children as an analgesic and/or antipyretic. Besides having a well-established safety and efficacy profile when used in appropriate doses, cases of NSAID-induced acute kidney injury (AKI) have been described in the pediatric population, particularly in the context of dehydration and in combination with other drugs. The ingestion of more than 400 mg/kg is associated with severe or life-threatening toxicity. This report is about two previously healthy adolescents, who developed AKI after taking high daily dose of ibuprofen as a pain reliever without any appropriate medical supervision. With these case reports, in addition to the side effect profiles of this analgesic, we would also like to present a certain therapeutic recommendation that we applied in these patients, and furthermore appeal to pediatricians to strictly set the indications for ibuprofen intake.
Adaptation, Translation and Validation of the Food Allergy Quality of Life Questionnaire-Parent Form (FAQLQ-PF): The Malay Version
Authors: Ibrahim Izyana Syazlin , Baharudin Noorhida , Isa Mohamad Rodi , Ismail Intan Hakimah , Mohamed-Yassin Mohamed-Syarif , Kamarudin Intan Kartika , Abdul Latiff Amir Hamzah , Zahedi Farah Dayana , Ali Adli , Arshad Azuin Izzati
Published: November 2021

Food allergy has a significant impact on the quality of life (QoL) of children and can be measured using The Food Allergy Quality of Life Questionnaire-Parent Form (FAQLQ-PF). This study aimed to adapt, translate the FAQLQ-PF into Malay and determine the validity and reliability of the translated version. This cross-sectional questionnaire validation study was conducted among parents of children (0 to 12 years old) with food allergies across five sites in Selangor and Kuala Lumpur, Malaysia. The FAQLQ-PF-Malay underwent cross-cultural adaptation, translation, validation (content, face and construct) and reliability assessment. Exploratory factor analysis, internal consistency and test-retest reliability analyses were used to examine its construct validity and reliability. Out of 150 children, the majority were between the age of 7 to 12 years old (41%) and were female (81%). Three subscales were identified, which were: (i) social and dietary implication, (ii) food anxiety and (iii) emotional and physical impact. Four items were eliminated because of weak factor loadings. The Cronbach’s alpha for each subscale ranged from 0.88 to 0.94, with an overall Cronbach’s alpha of 0.95. The intra-class correlation coefficient ranged from 0.54 (95% CI: 0.10–0.77) to 0.97 (95% CI: 0.90–0.99). The 26-item FAQLQ-PF-Malay retained the three-factor structure of the original FAQLQ-PF. The FAQLQ-PF-Malay is a valid and reliable tool to assess the QoL of Malaysian children with food allergies.
Circadian Alterations Increase with Progression in a Patient-Derived Cell Culture Model of Breast Cancer
Authors: Lin Hui-Hsien , Taylor Stephanie R. , Farkas Michelle E.
Published: November 2021

Circadian rhythm disruption can elicit the development of various diseases, including breast cancer. While studies have used cell lines to study correlations between altered circadian rhythms and cancer, these models have different genetic backgrounds and do not mirror the changes that occur with disease development. Isogenic cell models can recapitulate changes across cancer progression. Hence, in this study, a patient-derived breast cancer model, the 21T series, was used to evaluate changes to circadian oscillations of core clock protein transcription as cells progress from normal to malignant states. Three cell lines were used: H16N2 (normal breast epithelium), 21PT (atypical ductal hyperplasia), and 21MT-1 (invasive metastatic carcinoma). The cancerous cells are both HER2+. We assessed the transcriptional profiles of two core clock proteins, BMAL1 and PER2, which represent a positive and negative component of the molecular oscillator. In the normal H16N2 cells, both genes possessed rhythmic mRNA oscillations with close to standard periods and phases. However, in the cancerous cells, consistent changes were observed: both genes had periods that deviated farther from normal and did not have an anti-phase relationship. In the future, mechanistic studies should be undertaken to determine the oncogenic changes responsible for the circadian alterations found.
Clinical Outcomes of RTOG 9310 Protocol for Primary Central Nervous System Lymphoma: Single-Center Experience with 87 Patients
Authors: Kim Jinuk , Kim Tae Gyu , Lee Hyoun Wook , Kim Seok Hyun , Park Ji Eun , Lee Moonok , Kim Young Zoon
Published: November 2021

The Radiation Therapy Oncology Group (RTOG) 9310 protocol clinical trial established high-dose methotrexate (HDMTX) as the standard for primary central nervous system lymphoma (PCNSL). We aimed to investigate the RTOG 9310 protocol’s PCNSL outcomes by examining progression-free survival (PFS) and overall survival (OS) rates and determining the influential factors. Between 2007 and 2020, 87 patients were histopathologically diagnosed with PCNSL and treated with the RTOG 9310 protocol. All received HDMTX 2.5 g/m2 and vincristine 1.4 mg/m2/day for 1 day during weeks 1, 3, 5, 7, and 9, and procarbazine 100 mg/m2/day for 1 day during weeks 1, 5, and 9. Dexamethasone was administered on a standard tapering schedule from the first week to the sixth week. Whole brain radiotherapy (WBRT), consisting of 45 Gy for patients with less than a complete response to the chemotherapy or 36 Gy for complete responders, was started 1 week after the last dose of chemotherapy was administered. Within three weeks of the completion of WBRT, patients received two courses of cytarabine, which were separated by 3–4 weeks. Clinical, radiological, and histopathological characteristics were retrospectively reviewed. All patients completed five HDMTX cycles and a mean follow-up of 60.2 (range, 6–150) months. Twenty-eight (32.2%) patients experienced recurrence during follow-up. The mean time to recurrence was 21.8 months, while the mean PFS was 104.3 (95% confidence interval (CI), 90.6–118.0) months. Eleven (12.6%) patients died; the mean OS was 132.1 (95% CI, 122.2–141.9) months. The 3- and 5-year survival rates were 92.0% and 87.4%, respectively. One patient experienced acute renal failure, while the remainder tolerated any cytotoxic side effects. On multivariate analysis, the Eastern Cooperative Oncology Group performance score ≤ 2; the International Extranodal Lymphoma Study Group low-risk status; XBP-1, p53, and c-Myc negativity; homogenous enhancement; gross total resection, independently correlated with long PFS and OS. The RTOG 9310 protocol is effective for PCNSL and features good outcomes.
A Comparative Analysis of Machine Learning Models for the Prediction of Insurance Uptake in Kenya
Authors: Yego Nelson Kemboi , Kasozi Juma , Nkurunziza Joseph
Published: November 2021

The role of insurance in financial inclusion and economic growth, in general, is immense and is increasingly being recognized. However, low uptake impedes the growth of the sector, hence the need for a model that robustly predicts insurance uptake among potential clients. This study undertook a two phase comparison of machine learning classifiers. Phase I had eight machine learning models compared for their performance in predicting the insurance uptake using 2016 Kenya FinAccessHousehold Survey data. Taking Phase I as a base in Phase II, random forest and XGBoost were compared with four deep learning classifiers using 2019 Kenya FinAccess Household Survey data. The random forest model trained on oversampled data showed the highest F1-score, accuracy, and precision. The area under the receiver operating characteristic curve was furthermore highest for random forest; hence, it could be construed as the most robust model for predicting the insurance uptake. Finally, the most important features in predicting insurance uptake as extracted from the random forest model were income, bank usage, and ability and willingness to support others. Hence, there is a need for a design and distribution of low income based products, and bancassurance could be said to be a plausible channel for the distribution of insurance products.
Accelerating Causal Inference and Feature Selection Methods through G-Test Computation Reuse
Authors: Băncioiu Camil , Brad Remus
Published: November 2021

This article presents a novel and remarkably efficient method of computing the statistical G-test made possible by exploiting a connection with the fundamental elements of information theory: by writing the G statistic as a sum of joint entropy terms, its computation is decomposed into easily reusable partial results with no change in the resulting value. This method greatly improves the efficiency of applications that perform a series of G-tests on permutations of the same features, such as feature selection and causal inference applications because this decomposition allows for an intensive reuse of these partial results. The efficiency of this method is demonstrated by implementing it as part of an experiment involving IPC–MB, an efficient Markov blanket discovery algorithm, applicable both as a feature selection algorithm and as a causal inference method. The results show outstanding efficiency gains for IPC–MB when the G-test is computed with the proposed method, compared to the unoptimized G-test, but also when compared to IPC–MB++, a variant of IPC–MB which is enhanced with an AD–tree, both static and dynamic. Even if this proposed method of computing the G-test is presented here in the context of IPC–MB, it is in fact bound neither to IPC–MB in particular, nor to feature selection or causal inference applications in general, because this method targets the information-theoretic concept that underlies the G-test, namely conditional mutual information. This aspect grants it wide applicability in data sciences.
Statistical and Visual Analysis of Audio, Text, and Image Features for Multi-Modal Music Genre Recognition
Authors: Wilkes Ben , Vatolkin Igor , Müller Heinrich
Published: November 2021

We present a multi-modal genre recognition framework that considers the modalities audio, text, and image by features extracted from audio signals, album cover images, and lyrics of music tracks. In contrast to pure learning of features by a neural network as done in the related work, handcrafted features designed for a respective modality are also integrated, allowing for higher interpretability of created models and further theoretical analysis of the impact of individual features on genre prediction. Genre recognition is performed by binary classification of a music track with respect to each genre based on combinations of elementary features. For feature combination a two-level technique is used, which combines aggregation into fixed-length feature vectors with confidence-based fusion of classification results. Extensive experiments have been conducted for three classifier models (Naïve Bayes, Support Vector Machine, and Random Forest) and numerous feature combinations. The results are presented visually, with data reduction for improved perceptibility achieved by multi-objective analysis and restriction to non-dominated data. Feature- and classifier-related hypotheses are formulated based on the data, and their statistical significance is formally analyzed. The statistical analysis shows that the combination of two modalities almost always leads to a significant increase of performance and the combination of three modalities in several cases.
Analysis of Electromagnetic Information Leakage Based on Cryptographic Integrated Circuits
Authors: Sun Shaofei , Zhang Hongxin , Cui Xiaotong , Li Qiang , Dong Liang , Fang Xing
Published: November 2021

Cryptographic algorithm is the most commonly used method of information security protection for many devices. The secret key of cryptographic algorithm is usually stored in these devices’ registers. In this paper, we propose an electromagnetic information leakage model to investigate the relationship between the electromagnetic leakage signal and the secret key. The registers are considered as electric dipole models to illustrate the source of the electromagnetic leakage. The equivalent circuit of the magnetic field probe is developed to bridge the output voltage and the electromagnetic leakage signal. Combining them, the electromagnetic information leakage model’s function relationship can be established. Besides, an electromagnetic leakage model based on multiple linear regression is proposed to recover the secret key and the model’s effectiveness is evaluated by guess entropy. Near field tests are conducted in an unshielded ordinary indoor environment to investigate the electromagnetic side-channel information leakage. The experiment result shows the correctness of the proposed electromagnetic leakage model and it can be used to recover the secret key of the cryptographic algorithm.
Bearing Fault Diagnosis Using Refined Composite Generalized Multiscale Dispersion Entropy-Based Skewness and Variance and Multiclass FCM-ANFIS
Authors: Rostaghi Mostafa , Khatibi Mohammad Mahdi , Ashory Mohammad Reza , Azami Hamed
Published: November 2021

Bearing vibration signals typically have nonlinear components due to their interaction and coupling effects, friction, damping, and nonlinear stiffness. Bearing faults affect the signal complexity at various scales. Hence, measuring signal complexity at different scales is helpful to diagnosis of bearing faults. Numerous studies have investigated multiscale algorithms; nevertheless, multiscale algorithms using the first moment lose important complexity data. Accordingly, generalized multiscale algorithms have been recently introduced. The present research examined the use of refined composite generalized multiscale dispersion entropy (RCGMDispEn) based on the second moment (variance) and third moment (skewness) along with refined composite multiscale dispersion entropy (RCMDispEn) in bearing fault diagnosis. Moreover, multiclass FCM-ANFIS, which is a combination of adaptive network-based fuzzy inference systems (ANFIS), was developed to improve the efficiency of rotating machinery fault classification. According to the results, it is recommended that generalized multiscale algorithms based on variance and skewness be examined for diagnosis, along with multiscale algorithms, and be used to achieve an improvement in the results. The simultaneous usage of the multiscale algorithm and generalized multiscale algorithms improved the results in all three real datasets used in this study.
An Improved Calculation Formula of the Extended Entropic Chaos Degree and Its Application to Two-Dimensional Chaotic Maps
Authors: Inoue Kei
Published: November 2021

The Lyapunov exponent is primarily used to quantify the chaos of a dynamical system. However, it is difficult to compute the Lyapunov exponent of dynamical systems from a time series. The entropic chaos degree is a criterion for quantifying chaos in dynamical systems through information dynamics, which is directly computable for any time series. However, it requires higher values than the Lyapunov exponent for any chaotic map. Therefore, the improved entropic chaos degree for a one-dimensional chaotic map under typical chaotic conditions was introduced to reduce the difference between the Lyapunov exponent and the entropic chaos degree. Moreover, the improved entropic chaos degree was extended for a multidimensional chaotic map. Recently, the author has shown that the extended entropic chaos degree takes the same value as the total sum of the Lyapunov exponents under typical chaotic conditions. However, the author has assumed a value of infinity for some numbers, especially the number of mapping points. Nevertheless, in actual numerical computations, these numbers are treated as finite. This study proposes an improved calculation formula of the extended entropic chaos degree to obtain appropriate numerical computation results for two-dimensional chaotic maps.
A Hybrid Metaheuristic Based on Neurocomputing for Analysis of Unipolar Electrohydrodynamic Pump Flow
Authors: Khan Muhammad Fawad , Sulaiman Muhammad , Tavera Romero Carlos Andrés , Alkhathlan Ali
Published: November 2021

A unipolar electrohydrodynamic (UP-EHD) pump flow is studied with known electric potential at the emitter and zero electric potential at the collector. The model is designed for electric potential, charge density, and electric field. The dimensionless parameters, namely the electrical source number (Es), the electrical Reynolds number (ReE), and electrical slip number (Esl), are considered with wide ranges of variation to analyze the UP-EHD pump flow. To interpret the pump flow of the UP-EHD model, a hybrid metaheuristic solver is designed, consisting of the recently developed technique sine–cosine algorithm (SCA) and sequential quadratic programming (SQP) under the influence of an artificial neural network. The method is abbreviated as ANN-SCA-SQP. The superiority of the technique is shown by comparing the solution with reference solutions. For a large data set, the technique is executed for one hundred independent experiments. The performance is evaluated through performance operators and convergence plots.
Managing the Emotional Intensities of Gifted Students with Mindfulness Practices
Authors: Sisk Dorothy
Published: November 2021

The emotional intensities of gifted students affect not only their learning, but also the way they live and see the world. This article examines the Theory of Positive Disintegration of Dabrowski to explore the inner world of the gifted. The five levels of development and five overexcitabilities of Dabrowski represent an abundance of physical, sensual, creative, intellectual, and emotional energy that cause inner turmoil but can result in creative endeavors. The benefits of mindfulness practices to meeting the emotional needs of gifted students are presented with examples of deep listening, gratitude, and storytelling as mindfulness practices. A culminating activity of storytelling illustrates the integration of deep listening and gratitude and its effect on the sense of identity of gifted students.
Marginal Value of Vehicle-to-Grid Ancillary Service in a Power System with Variable Renewable Energy Penetration and Grid Side Flexibility
Authors: Kataoka Ryosuke , Ogimoto Kazuhiko , Iwafune Yumiko
Published: November 2021

Regulating the frequencies of power grids by controlling electric vehicle charging and discharging, known as vehicle-to-grid (V2G) ancillary services, is a promising and profitable means of providing flexibility that integrates variable renewable energy (VRE) into traditional power systems. However, the ancillary services market is a niche, and the scale, saturation, and time-dependency are unclear when assuming future changes in the power system structure. We studied the marginal value of V2G ancillary services as a balancing capacity of the power system operation on the load-frequency control (LFC) timescale and evaluated the reasonable maximum capacity of the LFC provided by V2G. As a case study, we assumed that the Japanese power system would be used under various VRE penetration scenarios and considered the limited availability time of V2G, based on the daily commuter cycle. The power system operation was modeled by considering pumped storage, interconnection lines, and thermal power–partial load operations. The results show that the marginal value of V2G was greater during the daytime than overnight, and the maximum cost saving (USD 705.6/EV/year) occurred during the daytime under the high-VRE scenario. Improving the value and size of V2G ancillary services required coordination with energy storage and excess VRE generation.
Determinants of Electrical and Thermal Energy Consumption in Hospitals According to Climate Zones in Poland
Authors: Cygańska Małgorzata , Kludacz-Alessandri Magdalena
Published: November 2021

Energy use in hospitals is higher than in other public buildings, so improving energy efficiency in healthcare buildings is a significant challenge in this sector of engineering. For this, it is necessary to know the various determinants of energy consumption. Until now, the main factor affecting energy consumption in healthcare facilities studied in the literature was hospital capacity. However, the commonly used variables connected with hospital size and the number of beds do not take into account the medical activities carried out in these buildings. Assuming that energy consumption in hospitals is multiple and shaped by many factors that overlap, not only on an individual level but also on a higher scale level, this study devises a more integrated approach to its determinants. This study aims to investigate the determinants of electrical energy costs (EEC) and thermal energy costs (TEC) in Polish hospitals with regard to factors related to their size, work intensity and climate zones. The analysis was carried out using financial and resource data from all Polish hospitals for the years 2010–2019. The study used a multivariate backward stepwise regression analysis. In order to use climate as a moderating variable, a sample of Polish hospitals from 16 Polish NUTS 2 was divided into four climate zones. This article provides new empirical evidence on the determinants of electricity consumption in Polish hospitals related to their size and medical activity, taking into account climate zone as a moderating variable. The results of the analysis show that both electricity and heat consumption in hospitals are positively related to the number of doctors, beds and the number of medical operations performed. As expected, larger hospitals seem to use more energy. Moreover, there is regional heterogeneity in energy consumption in hospitals related to the climatic zone in which they operate. The conducted analysis shows that Polish hospitals located in the warmest climatic zone are characterized by higher energy consumption than hospitals in the coldest zone. It especially regards EEC in surgery hospitals. The warmer the climate zones, the higher intensity in terms of the number of surgeries, the higher EEC. In terms of nonsurgical hospitals, the influence of climate zone on EEC was not observed. Knowing the factors influencing energy consumption in hospitals can facilitate the correct adoption of an energy-saving strategy in the health sector, which is a reasonable response to climate change and supports a healthy and sustainable future.
Experimental Analysis of GBM to Expand the Time Horizon of Irish Electricity Price Forecasts
Authors: Lynch Conor , O’Leary Christian , Sundareshan Preetham Govind Kolar , Akin Yavuz
Published: November 2021

In response to the inherent challenges of generating cost-effective electricity consumption schedules for dynamic systems, this paper espouses the use of GBM or Gradient Boosting Machine-based models for electricity price forecasting. These models are applied to data streams from the Irish electricity market and achieve favorable results, relative to the current state-of-the-art. Presently, electricity prices are published 10 h in advance of the trade day of interest. Using the forecasting methodology outlined in this paper, an estimation of these prices can be made available one day in advance of the official price publication, thus extending the time available to plan electricity utilization from the grid to be as cost effectively as possible. Extreme Gradient Boosting Machine (XGBM) models achieved a Mean Absolute Error (MAE) of 9.93 for data from 30 September 2018 to 12 December 2019 which is an 11.4% improvement on the avant-garde. LGBM models achieve a MAE score 9.58 on more recent data: the full year of 2020.