bluuebunny/crossref_metadata_2025 huggingface dataset:
Type 2 Diabetes Mellitus and Clinicopathological Tumor Characteristics in Women Diagnosed with Breast Cancer: A Systematic Review and Meta-Analysis
Authors: Zhang Fan , de Haan-Du Jing , Sidorenkov Grigory , Landman Gijs W. D. , Jalving Mathilde , Zhang Qingying , de Bock Geertruida H.
Published: October 2021

Poor prognosis caused by type 2 diabetes mellitus (T2DM) in women with breast cancer is conferred, while the association between T2DM and breast tumor aggressiveness is still a matter of debate. This study aimed to clarify the differences in breast cancer characteristics, including stage, size, lymph node status, grade, estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor (Her2), between patients with and without pre-existing T2DM. PubMed, Embase, and Web of Science were searched for studies from 1 January 2010 to 2 July 2021. Adjusted odds ratios (ORs) with 95% confidence intervals (CIs) were pooled by using a random effects model. T2DM was significantly associated with tumor stages III/IV versus cancers in situ and stages I/II (pooled ORs (pOR), 95% CI: 1.19; 1.04–1.36, p = 0.012), tumor size >20 versus ≤20 mm (pOR, 95% CI: 1.18; 1.04–1.35, p = 0.013), and lymph node invasion versus no involvement (pOR, 95% CI: 1.26; 1.05–1.51, p = 0.013). These findings suggest that women with T2DM are at a higher risk of late-stage tumors, large tumor sizes, and invasive lymph nodes at breast cancer diagnosis.
The miR-27a/FOXJ3 Axis Dysregulates Mitochondrial Homeostasis in Colorectal Cancer Cells
Authors: Barisciano Giovannina , Leo Manuela , Muccillo Livio , Pranzini Erica , Parri Matteo , Colantuoni Vittorio , Taddei Maria Letizia , Sabatino Lina
Published: October 2021

miR-27a plays a driver role in rewiring tumor cell metabolism. We searched for new miR-27a targets that could affect mitochondria and identified FOXJ3, an apical factor of mitochondrial biogenesis. We analyzed FOXJ3 levels in an in vitro cell model system that was genetically modified for miR-27a expression and validated it as an miR-27a target. We showed that the miR-27a/FOXJ3 axis down-modulates mitochondrial biogenesis and other key members of the pathway, implying multiple levels of control. As assessed by specific markers, the miR-27a/FOXJ3 axis also dysregulates mitochondrial dynamics, resulting in fewer, short, and punctate organelles. Consistently, in high miR-27a-/low FOXJ3-expressing cells, mitochondria are functionally characterized by lower superoxide production, respiration capacity, and membrane potential, as evaluated by OCR assays and confocal microscopy. The analysis of a mouse xenograft model confirmed FOXJ3 as a target and suggested that the miR-27a/FOXJ3 axis affects mitochondrial abundance in vivo. A survey of the TCGA-COADREAD dataset supported the inverse relationship of FOXJ3 with miR-27a and reinforced cellular component organization or biogenesis as the most affected pathway. The miR-27a/FOXJ3 axis acts as a central hub in regulating mitochondrial homeostasis. Its discovery paves the way for new therapeutic strategies aimed at restraining tumor growth by targeting mitochondrial activities.
The Evolving Role of Radiofrequency Guided Localisation in Breast Surgery: A Systematic Review
Authors: Tayeh Salim , Wazir Umar , Mokbel Kefah
Published: October 2021

Wire-guided localisation (WGL) has been the gold-standard for localising non-palpable breast lesions before excision. Due to its drawbacks, various wireless alternatives have been developed, including LOCalizer™, which is based on radio-frequency identification (RFID) technology. In this systematic review, we consulted EMBASE, Medline and PubMed databases using appropriate search terms regarding the use of RFID technology in the localisation of occult breast lesions. Retrospective and prospective studies were included if they quoted the number of patients, rate of successful placement, retrieval rate, margin positivity rate and the re-excision rate. In addition, studies comparing RFID to WGL were also included and analysed separately. Seven studies were included in this systematic review spanning 1151 patients and 1344 tags. The pooled deployment rate was 99.1% and retrieval rate was 100%. Re-excision rate was 13.9%. One complication was identified. Two studies compared RFID with WGL (128 vs. 282 patients respectively). For both techniques the re-excision rate was 15.6% (20/128 vs. 44/282 respectively, p value is 0.995). Based on our review, LOCalizer™ is safe and non-inferior to WGL in terms of successful localisation and re-excision rates. However, further research is required to assess the cost effectiveness of this approach and its impact on the aesthetic outcome compared with WGL and other wire free technologies to better inform decision making in service planning and provision.
Expression of CCRL2 Inhibits Tumor Growth by Concentrating Chemerin and Inhibiting Neoangiogenesis
Authors: Al Delbany Diana , Robert Virginie , Dubois-Vedrenne Ingrid , Del Prete Annalisa , Vernimmen Maxime , Radi Ayoub , Lefort Anne , Libert Frédérick , Wittamer Valérie , Sozzani Silvano , Parmentier Marc
Published: October 2021

CCRL2 belongs to the G protein-coupled receptor family and is one of the three chemerin receptors. It is considered as a non-signaling receptor, presenting chemerin to cells expressing the functional chemerin receptor ChemR23/CMKLR1 and possibly GPR1. In the present work, we investigate the role played by CCRL2 in mouse cancer models. Loss of function of Ccrl2 accelerated the development of papillomas in a chemical model of skin carcinogenesis (DMBA/TPA), whereas the growth of B16 and LLC tumor cell grafts was delayed. Delayed tumor growth was also observed when B16 and LLC cells overexpress CCRL2, while knockout of Ccrl2 in tumor cells reversed the consequences of Ccrl2 knockout in the host. The phenotypes associated with CCRL2 gain or loss of function were largely abrogated by knocking out the chemerin or Cmklr1 genes. Cells harboring CCRL2 could concentrate bioactive chemerin and promote the activation of CMKLR1-expressing cells. A reduction of neoangiogenesis was observed in tumor grafts expressing CCRL2, mimicking the phenotype of chemerin-expressing tumors. This study demonstrates that CCRL2 shares functional similarities with the family of atypical chemokine receptors (ACKRs). Its expression by tumor cells can significantly tune the effects of the chemerin/CMKLR1 system and act as a negative regulator of tumorigenesis.
Enhanced Delivery of Thermoresponsive Polymer-Based Medicine into Tumors by Using Heat Produced from Gold Nanorods Irradiated with Near-Infrared Light
Authors: Sano Kohei , Ishida Yumi , Tanaka Toshie , Mizukami Tatsuya , Nagayama Tomono , Haratake Yoshie , Munekane Masayuki , Yamasaki Toshihide , Mukai Takahiro
Published: October 2021

The aim of this study was to establish a drug delivery system (DDS) for marked therapy of tumors using a thermoresponsive polymer, polyoxazoline (POZ). The effectiveness of the following was investigated: (i) the delivery of gold nanorods (GNRs) to tumor tissues, (ii) heat production of GNR upon irradiation with near-infrared (NIR) light, and (iii) high accumulation of an intravenously injected radiolabeled POZ as a drug carrier in tumors by sensing heat produced by GNRs. When the GNR solution was irradiated with NIR light (808 nm), the solution temperature was increased both in a GNR-concentration-dependent manner and in a light-dose-dependent manner. POZ, with a lower critical solution temperature of 38 °C, was aggregated depending on the heat produced by the GNR irradiated by NIR light. When it was intratumorally pre-injected into colon26-tumor-bearing mice, followed by NIR light irradiation (GNR+/Light+ group), the tumor surface temperature increased to approximately 42 °C within 5 min. Fifteen minutes after irradiation with NIR light, indium-111 (111In)-labeled POZ was intravenously injected into tumor-bearing mice, and the radioactivity distribution was evaluated. The accumulation of POZ in the tumor was significantly (approximately 4-fold) higher than that in the control groups (GNR+/without NIR light irradiation (Light–), without injection of GNR (GNR–)/Light+, and GNR–/Light– groups). Furthermore, an in vivo confocal fluorescence microscopy study, using fluorescence-labeled POZ, revealed that uptake of POZ by the tumor could be attributed to the heat produced by GNR. In conclusion, we successfully established a novel DDS in which POZ could be efficiently delivered into tumors by using the heat produced by GNR irradiated with NIR light.
BOLD Coupling between Lesioned and Healthy Brain Is Associated with Glioma Patients’ Recovery
Authors: Romero-Garcia Rafael , Hart Michael G. , Bethlehem Richard A. I. , Mandal Ayan , Assem Moataz , Crespo-Facorro Benedicto , Gorriz Juan Manuel , Burke G. A. Amos , Price Stephen J. , Santarius Thomas , Erez Yaara , Suckling John
Published: October 2021

Predicting functional outcomes after surgery and early adjuvant treatment is difficult due to the complex, extended, interlocking brain networks that underpin cognition. The aim of this study was to test glioma functional interactions with the rest of the brain, thereby identifying the risk factors of cognitive recovery or deterioration. Seventeen patients with diffuse non-enhancing glioma (aged 22–56 years) were longitudinally MRI scanned and cognitively assessed before and after surgery and during a 12-month recovery period (55 MRI scans in total after exclusions). We initially found, and then replicated in an independent dataset, that the spatial correlation pattern between regional and global BOLD signals (also known as global signal topography) was associated with tumour occurrence. We then estimated the coupling between the BOLD signal from within the tumour and the signal extracted from different brain tissues. We observed that the normative global signal topography is reorganised in glioma patients during the recovery period. Moreover, we found that the BOLD signal within the tumour and lesioned brain was coupled with the global signal and that this coupling was associated with cognitive recovery. Nevertheless, patients did not show any apparent disruption of functional connectivity within canonical functional networks. Understanding how tumour infiltration and coupling are related to patients’ recovery represents a major step forward in prognostic development.
Estrogens and the Schrödinger’s Cat in the Ovarian Tumor Microenvironment
Authors: Gjorgoska Marija , Rižner Tea Lanišnik
Published: October 2021

Ovarian cancer is a heterogeneous disease affecting the aging ovary, in concert with a complex network of cells and signals, together representing the ovarian tumor microenvironment. As in the “Schrödinger’s cat” thought experiment, the context-dependent constituents of the—by the time of diagnosis—well-established tumor microenvironment may display a tumor-protective and -destructive role. Systemic and locally synthesized estrogens contribute to the formation of a pro-tumoral microenvironment that enables the sustained tumor growth, invasion and metastasis. Here we focus on the estrogen biosynthetic and metabolic pathways in ovarian cancer and elaborate their actions on phenotypically plastic, estrogen-responsive, aging immune cells of the tumor microenvironment, altogether highlighting the multicomponent-connectedness and complexity of cancer, and contributing to a broader understanding of the ovarian cancer biology.
Reversal of Bortezomib-Induced Neurotoxicity by Suvecaltamide, a Selective T-Type Ca-Channel Modulator, in Preclinical Models
Authors: Meregalli Cristina , Maricich Yuri , Cavaletti Guido , Canta Annalisa , Carozzi Valentina A. , Chiorazzi Alessia , Newbold Evan , Marmiroli Paola , Ceresa Cecilia , Diani Arthur , Papapetropoulos Spyros , Lee Margaret S.
Published: October 2021

This study evaluated suvecaltamide, a selective T-type calcium channel modulator, on chemotherapy-induced peripheral neurotoxicity (CIPN) and anti-cancer activity associated with bortezomib (BTZ). Rats received BTZ (0.2 mg/kg thrice weekly) for 4 weeks, then BTZ alone (n = 8) or BTZ+suvecaltamide (3, 10, or 30 mg/kg once daily; each n = 12) for 4 weeks. Nerve conduction velocity (NCV), mechanical threshold, β-tubulin polymerization, and intraepidermal nerve fiber (IENF) density were assessed. Proteasome inhibition was evaluated in peripheral blood mononuclear cells. Cytotoxicity was assessed in human multiple myeloma cell lines (MCLs) exposed to BTZ alone (IC50 concentration), BTZ+suvecaltamide (10, 30, 100, 300, or 1000 nM), suvecaltamide alone, or vehicle. Tumor volume was estimated in athymic nude mice bearing MCL xenografts receiving vehicle, BTZ alone (1 mg/kg twice weekly), or BTZ+suvecaltamide (30 mg/kg once daily) for 28 days, or no treatment (each n = 8). After 4 weeks, suvecaltamide 10 or 30 mg/kg reversed BTZ-induced reduction in NCV, and suvecaltamide 30 mg/kg reversed BTZ-induced reduction in IENF density. Proteasome inhibition and cytotoxicity were similar between BTZ alone and BTZ+suvecaltamide. BTZ alone and BTZ+suvecaltamide reduced tumor volume versus the control (day 18), and BTZ+suvecaltamide reduced tumor volume versus BTZ alone (day 28). Suvecaltamide reversed CIPN without affecting BTZ anti-cancer activity in preclinical models.
EZH2 Inhibition as New Epigenetic Treatment Option for Pancreatic Neuroendocrine Neoplasms (PanNENs)
Authors: April-Monn Simon Leonhard , Andreasi Valentina , Schiavo Lena Marco , Sadowski Martin Carl , Kim-Fuchs Corina , Buri Michelle Claudine , Ketkar Avanee , Maire Renaud , Di Domenico Annunziata , Schrader Jörg , Muffatti Francesca , Doglioni Claudio , Partelli Stefano , Falconi Massimo , Perren Aurel , Marinoni Ilaria
Published: October 2021

Pancreatic neuroendocrine neoplasms are epigenetically driven tumors, but therapies against underlying epigenetic drivers are currently not available in the clinical practice. We aimed to investigate EZH2 (Enhancer of Zest homolog) expression in PanNEN and the impact of EZH2 inhibition in three different PanNEN preclinical models. EZH2 expression in PanNEN patient samples (n = 172) was assessed by immunohistochemistry and correlated with clinico-pathological data. Viability of PanNEN cell lines treated with EZH2 inhibitor (GSK126) was determined in vitro. Lentiviral transduction of shRNA targeting EZH2 was performed in QGP1 cells, and cell proliferation was measured. Rip1TAG2 mice underwent GSK126 treatment for three weeks starting from week 10 of age. Primary cells isolated from PanNEN patients (n = 6) were cultivated in 3D as islet-like tumoroids and monitored for 10 consecutive days upon GSK126 treatment. Viability was measured continuously for the whole duration of the treatment. We found that high EZH2 expression correlated with higher tumor grade (p < 0.001), presence of distant metastases (p < 0.001), and shorter disease-free survival (p < 0.001) in PanNEN patients. Inhibition of EZH2 in vitro in PanNEN cell lines and in patient-derived islet-like tumoroids reduced cell viability and impaired cell proliferation, while inhibition of EZH2 in vivo in Rip1TAG2 mice reduced tumor burden. Our results show that EZH2 is highly expressed in high-grade PanNENs, and during disease progression it may contribute to aberrations in the epigenetic cellular landscape. Targeting EZH2 may represent a valuable epigenetic treatment option for patients with PanNEN.
Patient-Reported Financial Distress in Cancer: A Systematic Review of Risk Factors in Universal Healthcare Systems
Authors: Pauge Sophie , Surmann Bastian , Mehlis Katja , Zueger Andrea , Richter Luise , Menold Natalja , Greiner Wolfgang , Winkler Eva C.
Published: October 2021

Financial toxicity is a side effect of cancer that results from the perceived financial distress an individual may experience in the course of the disease. The purpose of this paper is to analyse underlying factors related to subjective financial distress in high-income countries with universal healthcare coverage. A systematic literature review was conducted to identify qualitative and quantitative studies of cancer patient-reported subjective financial distress by performing a search in the databases of PubMed, PsycINFO and CINAHL up to December 2020. A qualitative synthesis was performed linking the time-dependent occurrence of risk factors to derived categories of risk factors. Out of 4321 identified records, 30 quantitative and 16 qualitative studies were eligible. Classification of risk factors resulted in eight categories with a total of 34 subcategories. Subjective financial distress is primarily determined by pre-diagnosis sociodemographic- factors as well as financial and work factors that might change during the course of the disease. The design of healthcare and social security systems shapes the country-specific degree of subjective financial distress. Further research should focus on evolving multidisciplinary intervention schemes and multidimensional instruments for subjective financial distress to account for identified risk factors in universal healthcare systems more precisely.
Characteristics of Nephroblastoma/Nephroblastomatosis in Children with a Clinically Reported Underlying Malformation or Cancer Predisposition Syndrome
Authors: Welter Nils , Wagner Angelo , Furtwängler Rhoikos , Melchior Patrick , Kager Leo , Vokuhl Christian , Schenk Jens-Peter , Meier Clemens Magnus , Siemer Stefan , Gessler Manfred , Graf Norbert
Published: October 2021

(1) Background: about 10% of Wilms Tumor (WT) patients have a malformation or cancer predisposition syndrome (CPS) with causative germline genetic or epigenetic variants. Knowledge on CPS is essential for genetic counselling. (2) Methods: this retrospective analysis focused on 2927 consecutive patients with WTs registered between 1989 and 2017 in the SIOP/GPOH studies. (3) Results: Genitourinary malformations (GU, N = 66, 2.3%), Beckwith-Wiedemann spectrum (BWS, N = 32, 1.1%), isolated hemihypertrophy (IHH, N = 29, 1.0%), Denys-Drash syndrome (DDS, N = 24, 0.8%) and WAGR syndrome (N = 20, 0.7%) were reported most frequently. Compared to others, these patients were younger at WT diagnosis (median age 24.5 months vs. 39.0 months), had smaller tumors (349.4 mL vs. 487.5 mL), less often metastasis (8.2% vs. 18%), but more often nephroblastomatosis (12.9% vs. 1.9%). WT with IHH was associated with blastemal WT and DDS with stromal subtype. Bilateral WTs were common in WAGR (30%), DDS (29%) and BWS (31%). Chemotherapy induced reduction in tumor volume was poor in DDS (0.4% increase) and favorable in BWS (86.9% reduction). The event-free survival (EFS) of patients with BWS was significantly (p = 0.002) worse than in others. (4) Conclusions: CPS should be considered in WTs with specific clinical features resulting in referral to a geneticist. Their outcome was not always favorable.
Immunonutritive Scoring for Patients with Hepatocellular Carcinoma Undergoing Transarterial Chemoembolization: Evaluation of the CALLY Index
Authors: Müller Lukas , Hahn Felix , Mähringer-Kunz Aline , Stoehr Fabian , Gairing Simon Johannes , Michel Maurice , Foerster Friedrich , Weinmann Arndt , Galle Peter Robert , Mittler Jens , Pinto dos Santos Daniel , Pitton Michael Bernhard , Düber Christoph , Kloeckner Roman
Published: October 2021

The novel CRP–albumin–lymphocyte (CALLY) index is an improved immunonutritive scoring system, based on serum C-reactive protein (CRP), serum albumin, and the lymphocyte count. It has shown promise as a prognostic index for patients with hepatocellular carcinoma (HCC) undergoing resections. This study evaluated the prognostic ability of the CALLY index for patients with HCC undergoing transarterial chemoembolization (TACE). We retrospectively identified 280 treatment-naïve patients with HCC that underwent an initial TACE at our institution, between 2010 and 2020. We compared the CALLY index to established risk factors in univariate and multivariate regression analyses for associations with median overall survival (OS). A low CALLY score was associated with low median OS (low vs. high CALLY: 9.0 vs. 24.0 months, p < 0.001). In the multivariate analysis, the CALLY index remained an independent prognostic predictor (p = 0.008). Furthermore, all factors of the CALLY index reached significance in univariate and in-depth multivariate analyses. However, the concordance index (C-index) of the CALLY index (0.60) was similar to the C-indices of established immunonutritive and inflammation scoring systems (range: 0.54 to 0.63). In conclusion, the CALLY index showed promise as a stratification tool for patients with HCC undergoing TACE. Notably, the CALLY index was not superior to other immunonutritive and inflammation scoring systems in predicting the median OS. Thus, future studies should re-evaluate the mathematical calculation of the index, particularly the contributions of individual parameters.
USP28: Oncogene or Tumor Suppressor? A Unifying Paradigm for Squamous Cell Carcinoma
Authors: Prieto-Garcia Cristian , Tomašković Ines , Shah Varun Jayeshkumar , Dikic Ivan , Diefenbacher Markus
Published: October 2021

Squamous cell carcinomas are therapeutically challenging tumor entities. Low response rates to radiotherapy and chemotherapy are commonly observed in squamous patients and, accordingly, the mortality rate is relatively high compared to other tumor entities. Recently, targeting USP28 has been emerged as a potential alternative to improve the therapeutic response and clinical outcomes of squamous patients. USP28 is a catalytically active deubiquitinase that governs a plethora of biological processes, including cellular proliferation, DNA damage repair, apoptosis and oncogenesis. In squamous cell carcinoma, USP28 is strongly expressed and stabilizes the essential squamous transcription factor ΔNp63, together with important oncogenic factors, such as NOTCH1, c-MYC and c-JUN. It is presumed that USP28 is an oncoprotein; however, recent data suggest that the deubiquitinase also has an antineoplastic effect regulating important tumor suppressor proteins, such as p53 and CHK2. In this review, we discuss: (1) The emerging role of USP28 in cancer. (2) The complexity and mutational landscape of squamous tumors. (3) The genetic alterations and cellular pathways that determine the function of USP28 in squamous cancer. (4) The development and current state of novel USP28 inhibitors.
An Emerging Role of PRRT2 in Regulating Growth Cone Morphology
Authors: Savino Elisa , Guarnieri Fabrizia Claudia , Tsai Jin-Wu , Corradi Anna , Benfenati Fabio , Valtorta Flavia
Published: October 2021

Mutations in the PRRT2 gene are the main cause for a group of paroxysmal neurological diseases including paroxysmal kinesigenic dyskinesia, episodic ataxia, benign familial infantile seizures, and hemiplegic migraine. In the mature central nervous system, the protein has both a functional and a structural role at the synapse. Indeed, PRRT2 participates in the regulation of neurotransmitter release, as well as of actin cytoskeleton dynamics during synaptogenesis. Here, we show a role of the protein also during early stages of neuronal development. We found that PRRT2 accumulates at the growth cone in cultured hippocampal neurons. Overexpression of the protein causes an increase in the size and the morphological complexity of growth cones. In contrast, the growth cones of neurons derived from PRRT2 KO mice are smaller and less elaborated. Finally, we demonstrated that the aberrant shape of PRRT2 KO growth cones is associated with a selective alteration of the growth cone actin cytoskeleton. Our data support a key role of PRRT2 in the regulation of growth cone morphology during neuronal development.
Body Shape Indices in Adolescents Based on the 2009–2012 Korea National Health and Nutrition Examination Survey
Authors: Kwak Byung Ok , Lim Jisun , Chung Sochung
Published: October 2021

A Body Shape Index (ABSI) is a recently proposed index for standardizing waist circumference (WC) for body mass index (BMI) and height in adults, using 2/3 and 1/2 as scaling exponents, respectively. However, ABSI has limited applicability to children and adolescents, as the relationship between height and weight changes with age and varies according to sex. This study aimed to investigate whether ABSI can be applied to adolescents and to analyze the relationships among BMI, WC, height, weight, and body shape index (BSI) in Korean adolescents. The data of 1023 adolescents aged 10–19 years from the 2009–2012 Korea National Health and Nutrition Examination Survey were collected. Body measurements (height, weight, WC, and BMI) were analyzed to estimate the BSI using log-linear regression. The scaling exponents for standardizing WC for weight and height were estimated according to age (per year) and sex. The scaling exponents for standardizing WC for weight and height were 0.698 and −1.090 for boys and 0.646 and −0.855 for girls, respectively. The exponents also differed according to age. BSI was negatively correlated with height, weight, and BMI in boys and girls, and these correlations differed in direction from those in adults. ABSI cannot be applied to adolescents. In adolescents, the BSI is dependent on age and sex and is associated with growth and puberty. Further studies are required to evaluate the association between BSI and other biomarkers, to improve its applicability as a parameter for predicting the risk of chronic diseases in adolescents.
Changes in Protein Structural Motifs upon Post-Translational Modification in Kidney Cancer
Authors: Tikhonov Dmitry , Kulikova Liudmila , Rudnev Vladimir , Kopylov Arthur T. , Taldaev Amir , Stepanov Alexander , Malsagova Kristina , Izotov Alexander , Enikeev Dmitry , Potoldykova Natalia , Kaysheva Anna
Published: October 2021

Post-translational modification (PTM) leads to conformational changes in protein structure, modulates the biological function of proteins, and, consequently, changes the signature of metabolic transformations and the immune response in the body. Common PTMs are reversible and serve as a mechanism for modulating metabolic trans-formations in cells. It is likely that dysregulation of post-translational cellular signaling leads to abnormal proliferation and oncogenesis. We examined protein PTMs in the blood samples from patients with kidney cancer. Conformational changes in proteins after modification were analyzed. The proteins were analyzed using ultra-high resolution HPLC-MS/MS and structural analysis was performed with the AMBER and GROMACS software packages. Fifteen proteins containing PTMs were identified in blood samples from patients with kidney cancer. For proteins with PDB structures, a comparative analysis of the structural changes accompanying the modifications was performed. Results revealed that PTMs are localized in stable and compact space protein globule motifs that are exposed to a solvent. The phenomenon of modification is accompanied, as a rule, by an increase in the area available for the solvent of the modified amino acid residue and its active environment.
Spectrum Bias and Individual Strengths of SARS-CoV-2 Serological Tests—A Population-Based Evaluation
Authors: Einhauser Sebastian , Peterhoff David , Niller Hans Helmut , Beileke Stephanie , Günther Felix , Steininger Philipp , Burkhardt Ralph , Heid Iris M. , Pfahlberg Annette B. , Überla Klaus , Gefeller Olaf , Wagner Ralf
Published: October 2021

Antibody testing for determining the SARS-CoV-2 serostatus was rapidly introduced in early 2020 and since then has been gaining special emphasis regarding correlates of protection. With limited access to representative samples with known SARS-CoV-2 infection status during the initial period of test development and validation, spectrum bias has to be considered when moving from a “test establishment setting” to population-based settings, in which antibody testing is currently implemented. To provide insights into the presence and magnitude of spectrum bias and to estimate performance measures of antibody testing in a population-based environment, we compared SARS-CoV-2 neutralization to a battery of serological tests and latent class analyses (LCA) in a subgroup (n = 856) of the larger population based TiKoCo-19 cohort (n = 4185). Regarding spectrum bias, we could proof notable differences in test sensitivities and specificities when moving to a population-based setting, with larger effects visible in earlier registered tests. While in the population-based setting the two Roche ELECSYS anti-SARS-CoV-2 tests outperformed every other test and even LCA regarding sensitivity and specificity in dichotomous testing, they didn’t provide satisfying quantitative correlation with neutralization capacity. In contrast, our in-house anti SARS-CoV-2-Spike receptor binding domain (RBD) IgG-ELISA (enzyme-linked-immunosorbant assay) though inferior in dichotomous testing, provided satisfactory quantitative correlation and may thus represent a better correlate of protection. In summary, all tests, led by the two Roche tests, provided sufficient accuracy for dichotomous identification of neutralizing sera, with increasing spectrum bias visible in earlier registered tests, while the majority of tests, except the RBD-ELISA, didn’t provide satisfactory quantitative correlations.
What Is a Solitary Keratoacanthoma? A Benign Follicular Neoplasm, Frequently Associated with Squamous Cell Carcinoma
Authors: Ogita Azusa , Ansai Shin-ichi
Published: October 2021

We present histopathological criteria for diagnosing keratoacanthoma (KA). In KA, four histological stages are recognized, which are the early/proliferative stage, well-developed stage, regressing stage and regressed stage. In diagnosing KA, we emphasize that KA consists of the proliferation of enlarged pale pink cells with ground glass-like cytoplasm without nuclear atypia, other than crateriform architecture. KA sometimes exhibits malignant transformation within the lesions. We describe the characteristics of benign and malignant epithelial crateriform tumors that should be differentiated from KA. We also present the data of histopathological diagnosis of lesions clinically diagnosed as KA, its natural course and related lesions after partial biopsy, and incidence of crateriform epithelial neoplasms. Based on these data, we recommend complete excision of the lesion when KA is clinically suspected, especially when the lesion is located on a sun-exposed area of an elderly patient. If complete excision is impossible, partial excision of a sufficient specimen with intact architecture is required. In such a case, however, careful investigation after biopsy will be needed, even if the histopathological diagnosis is KA, because there is some possibility that a conventional SCC lesion remains in the residual tissue.
Improved Deep Q-Network for User-Side Battery Energy Storage Charging and Discharging Strategy in Industrial Parks
Authors: Chen Shuai , Jiang Chengpeng , Li Jinglin , Xiang Jinwei , Xiao Wendong
Published: October 2021

Battery energy storage technology is an important part of the industrial parks to ensure the stable power supply, and its rough charging and discharging mode is difficult to meet the application requirements of energy saving, emission reduction, cost reduction, and efficiency increase. As a classic method of deep reinforcement learning, the deep Q-network is widely used to solve the problem of user-side battery energy storage charging and discharging. In some scenarios, its performance has reached the level of human expert. However, the updating of storage priority in experience memory often lags behind updating of Q-network parameters. In response to the need for lean management of battery charging and discharging, this paper proposes an improved deep Q-network to update the priority of sequence samples and the training performance of deep neural network, which reduces the cost of charging and discharging action and energy consumption in the park. The proposed method considers factors such as real-time electricity price, battery status, and time. The energy consumption state, charging and discharging behavior, reward function, and neural network structure are designed to meet the flexible scheduling of charging and discharging strategies, and can finally realize the optimization of battery energy storage benefits. The proposed method can solve the problem of priority update lag, and improve the utilization efficiency and learning performance of the experience pool samples. The paper selects electricity price data from the United States and some regions of China for simulation experiments. Experimental results show that compared with the traditional algorithm, the proposed approach can achieve better performance in both electricity price systems, thereby greatly reducing the cost of battery energy storage and providing a stronger guarantee for the safe and stable operation of battery energy storage systems in industrial parks.
Prospective Teachers’ Representations on the Concept of Force
Authors: Martini Berta , Michelini Marisa , Stefanel Alberto , Tombolato Monica
Published: October 2021

We present a study on teacher education and, in particular, on Physics. Our assumption is that General Didactics and Disciplinary Didactic constitute two fundamental components of teachers’ professional development and therefore both must be used to interpret didactic phenomena adequately. This research involves a sample of 274 prospective teachers, enrolled in the Primary Education Sciences degrees in three Italian Universities (Milano Bicocca, Udine, Urbino,). It concerns the study of the spontaneous representations produced by students to foster understanding of the force concept and on the reasons given to motivate their effectiveness on an educational level and disciplinary one. The research tools and methods were developed by crossing the literature of General Didactics and Physics Education, identifying analytical categories that emerge from two different and complementary perspectives. In the broad spectrum of students’ conceptions, given by this double perspective, some aspects stand out: most of the representations do not include the representation of the forces at play, but rather imply a precise didactic approach inherent to the concept of force. This is confirmed by the analysis of the didactic and disciplinary motivations, in which a frequent identification of the two types of motivations emerges.
A Low-Power GPIO-Based Size Sensor to Monitor the Imbibition of Corn Seeds Beneath Soil
Authors: Hamed Ehab A. , Athas Jordan , Zhang Xincheng , Ashenden Noah , Lee Inhee
Published: October 2021

Seed imbibition, absorption of water by a dry seed, is an essential process in which embryo hydration and root establishment occur. In natural environments, this process occurs beneath the soil, making it difficult to observe preliminary growth of seeds. This paper presents a new technique for tracking the imbibition of corn seeds. The proposed system is designed to measure imbibition through seed expansion and wirelessly transmit data, permitting the system to remain beneath the soil with the subject seed. The system consists of low-cost commercial off-the-shelf components and 3D-printed probes. The proposed system is optimized to measure the size of multiple seeds with a single Analog-to-Digital Converter (ADC) pin by utilizing the General-Purpose Input Output (GPIO) pins of the microcontroller, to reconfigure connections to supply voltage or ground. The circuit design of the system shows low power consumption compared to other conventional circuits and utilizes fewer components by taking advantage of the microcontroller GPIOs. Additionally, the proposed circuit design shows less error and insensitivity to the supply voltage variations.
Inverse Design of a Microstrip Meander Line Slow Wave Structure with XGBoost and Neural Network
Authors: Zhu Yijun , Xie Yang , Bai Ningfeng , Sun Xiaohan
Published: October 2021

We present a new machine learning (ML) deep learning (DL) synthesis algorithm for the design of a microstrip meander line (MML) slow wave structure (SWS). Exact numerical simulation data are used in the training of our network as a form of supervised learning. The learning results show that the training mean squared error is as low as 5.23 × 10−2 when using 900 sets of data. When the desired performance is reached, workable geometry parameters can be obtained by this algorithm. A D-band MML SWS with 20 GHz bandwidth at 160 GHz center frequency is then designed using the auto-design neural network (ADNN). A cold test shows that its phase velocity varies by 0.005 c, and the transmission rate of a 50-period SWS is greater than −5 dB with the reflectivity below −15 dB when the frequency is from 150 to 170 GHz. Particle-in-cell (PIC) simulation also illustrates that a maximum power of 3.2 W is reached at 160 GHz with 34.66 dB gain and output power greater than 1 W from 152 to 168 GHz.
A Three-Stage Data-Driven Approach for Determining Reaction Wheels’ Remaining Useful Life Using Long Short-Term Memory
Authors: Islam Md Sirajul , Rahimi Afshin
Published: October 2021

Reaction wheels are widely used in the attitude control system of small satellites. Unfortunately, reaction wheels failure restricts the efficacy of a satellite, and it is one of the many reasons leading to premature abandonment of the satellites. This study observes the measurable system parameter of a faulty reaction wheel induced with incipient fault to estimate the remaining useful life of the reaction wheels. We achieve this goal in three stages, as none of the observable system parameters are directly related to the health of a reaction wheel. In the first stage, we identify the necessary observable system parameter and predict the future of these parameters using sensor acquired data and a long short-term memory recurrent neural network. In the second stage, we estimate the health index parameter using a multivariate long short-term memory network. In the third stage, we predict the remaining useful life of reaction wheels based on historical data of the health index parameter. Normalized root mean squared error is used to evaluate the performance of the various models in each stage. Additionally, three different timespans (short, moderate, and extended in the scale of small satellite orbit times) are simulated and tested for the performance of the proposed methodology regarding the malfunction of reaction wheels. Furthermore, the robustness of the proposed method to missing values, input frequency, and noise is studied. The results show promising performance for the proposed scheme with accuracy in predicting health index parameter around 0.01–0.02 normalized root mean squared error, the accuracy in prediction of RUL of 1%–2.5%, and robustness to various uncertainty factors, as discussed above.
Short-Term Cooperative Operational Scheme of Distribution System with High Hosting Capacity of Renewable-Energy-Based Distributed Generations
Authors: Oh Chan-Hyeok , Choi Joon-Ho , Yun Sang-Yun , Ahn Seon-Ju
Published: October 2021

As the interconnection of renewable-energy-based distributed generations (DGs) to the distribution system increases, the local and temporary voltage and current problems, which are difficult to resolve with the existing operation method, are becoming serious. In this study, we propose a short-term operational method that can effectively resolve voltage and current violations caused by instantaneous output fluctuations of DGs in a system with a high hosting capacity of renewable energy sources. To achieve the objectives, a modified heuristic network reconfiguration method, and a method determining the maximum power output limit of individual DGs are proposed. We propose a cooperative method for controlling the power output fluctuations of renewable-energy-based DGs, which includes voltage control, network reconfiguration, and power curtailment. The proposed algorithm was verified through case studies by using a test system implemented in MATLAB environments. It can effectively resolve violations caused by DGs while minimizing the number of switching operations and power curtailment. The proposed method is an appropriate operation method to be applied to the real system as it can cope with the instantaneous output fluctuation of DGs, which was not dealt with in the existing operation method.
The Influence of the Nature of Redox-Active Moieties on the Properties of Redox-Active Ionic Liquids and on Their Use as Electrolyte for Supercapacitors
Authors: Borchers Philipp S. , Gerlach Patrick , Liu Yihan , Hager Martin D. , Balducci Andrea , Schubert Ulrich S.
Published: October 2021

In this work, two new redox-active ionic liquids, one based on 2,2,6,6-tetramethylpiperidine-N-oxide and the other based on 4,4′-bipyridine, are synthesized and characterized. A ferrocene-based redox-active ionic liquid is used for referencing the results. All ionic liquids are formed via salt-metathesis from halogenate to bis(trifluoromethylsulfonyl)imide. Their fundamental thermal characteristics are assessed with differential scanning calorimetry. While the imidazolium ionic liquids show no melting point, the phase transition is well observable for the viologen-based ionic liquid. The properties of the neat redox-active ionic liquids and of binary mixtures containing these ionic liquids (0.1 m) and 1-butyl-1-methyl pyrrolidinium-bis(trifluoromethylsulfonyl)imide have been investigated. Finally, the use of these binary mixtures in combination with activated carbon-based electrodes has been considered in view of the use of these redox-active electrolytes in supercapacitors.
A Parameter-Free Approach for Fault Section Detection on Distribution Networks Employing Gated Recurrent Unit
Authors: Shadi Mohammad Reza , Mirshekali Hamid , Dashti Rahman , Ameli Mohammad-Taghi , Shaker Hamid Reza
Published: October 2021

Faults in distribution networks can result in severe transients, equipment failure, and power outages. The quick and accurate detection of the faulty section enables the operator to avoid prolonged power outages and economic losses by quickly retrieving the network. However, the occurrence of diverse fault types with various resistances and locations and the highly non-linear nature of distribution networks make fault section detection challenging for numerous conventional techniques. This study presents a cutting-edge deep learning-based algorithm to distinguish fault sections in distribution networks to address these issues. The proposed gated recurrent unit model utilizes only two samples of the angle between the voltage and current on either side of the feeders, which record by smart feeder meters, to detect faulty sections in real time. When a network fault occurs, the protection relays trigger the trip command for the breakers. Immediately, the angle data are obtained from all smart feeder meters of the network, which comprises a pre-fault sample and a post-fault sample. The data are then employed as an input to the pre-trained gated recurrent unit model to determine the faulted line. The performance of this novel algorithm was validated through simulations of various fault types in the IEEE-33 bus system. The model recognizes the faulty section with competitive performance in terms of accuracy.
The Situation of Households on the Energy Market in the European Union: Consumption, Prices, and Renewable Energy
Authors: Matuszewska-Janica Aleksandra , Żebrowska-Suchodolska Dorota , Mazur-Dudzińska Agnieszka
Published: October 2021

Energy plays a crucial role in the modern world. The acquisition and consumption of energy is unfortunately associated not only with economic development or the facilitation of everyday life, but also with a negative impact on the environment. To prevent these, measures are being taken which are part of a broad programme referred to as sustainable energy development (SED). A special place among energy consumers is occupied by households, as access to energy is a fundamental factor affecting the quality of life. The aim of this paper is to look at and assess the current situation of the household sector in the EU energy market in the context of SED and to point out similarities and differences between EU countries. The analysis considers factors based on SED indicators: final energy consumption per capita, energy prices offered to households, and the share of renewable energy in household energy consumption. The k-means method was used as a research tool. The results obtained indicate first of all that the EU countries are highly differentiated in terms of the analysed factors. It can be said that these differences result not only from the wealth of a given country, geographical location, or natural possibilities to use renewable energy sources, but mainly from the energy policies implemented in individual countries.
Multifrequency Impedance Tomography System for Research on Environmental and Thermal Processes
Authors: Porzuczek Jan
Published: October 2021

The possibility for spatial and temporal monitoring of environmental, chemical or thermal processes is of high importance for their better understanding thus control and optimization. Therefore, measurement methods that enable such opportunities might be especially valuable for researchers and process engineers. For this reason, in this paper the novel Electrical Impedance Tomography system is proposed that enables the visualization of the processes in which the electrical conductivity of material is changing. The proposed EIT system is based mostly on general purpose equipment. It consists of three laboratory-grade devices: a signal generator, a switching device and a data acquisition card for voltage measurement. In addition to those devices, the current source was constructed to complete the system. The EIT system was designed to have the ability of sourcing the current of frequency up to 250 kHz. A set of validation experiments were carried out to verify the EIT system accuracy. The validation tests consisted of object detection, distinguishing between objects of different conductivity, multifrequency imaging and visualization of slow-changing processes. The obtained results were also compared with the numerical simulations. The proposed system was proven to have the ability of correct imaging of irregularity inside the area of the sensor.
Integrated Vapor Compression Chiller with Bottoming Organic Rankine Cycle and Onsite Low-Grade Renewable Energy
Authors: Tauseef Nasir Muhammad , Chukwuemeka Ekwonu Michael , Esfahani Javad Abolfazali , Kim Kyung Chun
Published: October 2021

The present study offers a scheme to improve the performance of existing large-scale chillers. The system involves raising the temperature of the chiller’s cooling water stream using renewable energy sources by incorporating an organic Rankine cycle (ORC). The thermal analysis was conducted by raising the temperature of one-third of the approximately 200 ton chiller’s cooling water. The investigation was considered for ORC evaporator inlet temperature of 90~120 °C by the step of 10 °C. Various working fluids for the different ORC evaporator inlet temperatures were examined. Sensitivity analyses conducted on the degree of superheating, degree of subcooling, condenser saturation temperature, pinch point temperature differences of the ORC evaporator and condenser, and the mass flowrates of the heating and cooling streams were also reported. Genetic algorithm was employed to carry out the optimization. The best options for the ORC working fluid at the heating source ORC evaporator inlet temperatures of 90 °C was found to be DME, presenting an improvement of 48.72% in comparison with the rated coefficient of performance (COP) value of the VCC, with a renewable energy input requirement of 710 kW. At the heat source temperatures of 100 °C and 110 °C, butene, which presented an improvement in the COP equal to 48.76% and 68.85%, respectively, with the corresponding renewable energy requirements of 789.6 kW and 852 kW, was found to be the ideal candidate. Meanwhile, at the heat source inlet temperature of 120 °C, R1233zd (E), representing an improvement of 140.88% with the renewable energy input of around 1061 kW, was determined to be the most favorable ORC working fluid candidate.