bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparative Agent-Based Simulations on Levels of Multiplicity Using a Network Regression: A Mobile Dating Use-Case
Authors: Shaheen Joseph A. E. , Henley Collin , McKenna Liam , Hoang Steven , Abdulwahab Fatma
Published: February 2022

We demonstrate the use of agent-based models to simulate the interactions of two mobile dating applications that possess divergent interaction features. We reproduce several expected outcomes when compared to extant literature. We also demonstrate the use of a standard social network analysis technique—the network regression, Multiple Regression Quadratic Assignment Procedure—in conducting a principled and interpretable comparison between the two models with strong results. This combined approach is novel and allows complex system modelers who utilize agent-based models to reduce their reliance on idealized network structures (small world, scale-free, erdos-renyi) when applying underlying network interactions to agent-based models that can often skew results and mislead from a full picture of system-level properties. This work serves as a proof-of-concept in the integration of classical social network analysis methods and contemporary agent-based modeling to compare software designs and to enhance the policy-generation process of online social networks.
Progress in Topological Mechanics
Authors: Zheng Shengjie , Duan Guiju , Xia Baizhan
Published: February 2022

Topological mechanics is rapidly emerging as an attractive field of research where mechanical waveguides can be designed and controlled via topological methods. With the development of topological phases of matter, recent advances have shown that topological states have been realized in the elastic media exploiting analogue quantum Hall effect, analogue quantum spin Hall effect, analogue quantum valley Hall effect, higher-order topological physics, topological pump, topological lattice defects and so on. This review aims to introduce the experimental and theoretical achievements with defect-immune protected elastic waves in mechanical systems based on the abovementioned methods, respectively. From these discussions, we predict the possible perspective of topological mechanics.
3-D Sound Image Reproduction Method Based on Spherical Harmonic Expansion for 22.2 Multichannel Audio
Authors: Iwai Kenta , Suzuki Hiromu , Nishiura Takanobu
Published: February 2022

In this paper, we propose a three-dimensional (3-D) sound image reproduction method based on spherical harmonic (SH) expansion for 22.2 multichannel audio. 22.2 multichannel audio is a 3-D sound field reproduction system that has been developed for ultra-high definition television (UHDTV). This system can reproduce 3-D sound images by simultaneously driving 22 loudspeakers and two sub-woofers. To control the 3-D sound image, vector base amplitude panning (VBAP) is conventionally used. VBAP can control the direction of 3-D sound image by weighting the input signal and emitting it from three loudspeakers. However, VBAP cannot control the distance of the 3-D sound image because it calculates the weight by only considering the image’s direction. To solve this problem, we propose a novel 3-D sound image reconstruction method based on SH expansion. The proposed method can control both the direction and distance of the 3-D sound image by controlling the sound directivity on the basis of spherical harmonics (SHs) and mode matching. The directivity of the 3-D sound image is obtained in the SH domain. In addition, the distance of the 3-D sound image is represented by the mode strength. The signal obtained by the proposed method is then emitted from loudspeakers and the 3-D sound image can be reproduced accurately with consideration of not only the direction but also the distance. A number of experimental results show that the proposed method can control both the direction and distance of 3-D sound images.
Nano-Architectonics of Antibiotic-Loaded Polymer Particles as Vehicles for Active Molecules
Authors: Forna Norin , Damir Daniela , Duceac Letitia Doina , Dabija Marius Gabriel , Calin Gabriela , Ichim Daniela Luminita , Gutu Cristian , Grierosu Carmen , Eva Lucian , Ciuhodaru Mădălina Irina , Goroftei Elena Roxana Bogdan , Banu Elena Ariela , Stafie Liviu , Gabriela Ciolpan , Mitrea Geta , Marcu Constantin
Published: February 2022

Recently, nanotechnology research studies have been proven that use of various nanoparticles as drug delivery systems to target and to annihilate pathogenic microorganisms may be a good solution for prevention and treatment of severe infection. In the last few years, antimicrobial drug encapsulation into nano-sized systems has materialized as a promising alternative that increased drug efficacy and minimized adverse effects. Physicochemical properties of erythromycin-loaded polymer nanoparticles were assessed using particle size distribution, HPLC, FTIR, TG/DTA, and SEM characterization techniques. The as-prepared samples exhibited an average particle size of 340 and 270 nm, respectively, with erythromycin content of 99.7% in both samples. From the release profile of erythromycin from PLA/PLGA, a prolonged drug release can be observed from both Ery-PLA and Ery-PLGA nanostructures. Morphology images exhibited spherical, rigid, and ring-shaped nanoparticles. Thermal analytical study in the case of Ery-PLA and Ery-PLGA samples showed that pure drug has an endothermic peak at around 150 °C assigned to a melting point. The antibiotic melting peak disappeared for both antibiotic-loaded PLA and PLGA nanoparticles thermographs, denoting the presence of erythromycin. This indicates that the antibiotic is uniformly dispensed throughout the host polymer matrix at nanometer scale. FTIR spectra of Ery-PLA and Ery-PLGA nano-architectures with almost similar peaks indicated no alteration in chemical structure of drug-loaded polymer nanoparticles.
Salivary Gland Disorders in Pediatric Patients: A 20 Years’ Experience
Authors: Lo Giudice Giorgio , Marra Paola Martina , Colella Chiara , Itro Angelo , Tartaro Gianpaolo , Colella Giuseppe
Published: February 2022

Salivary gland disorders are uncommon in children; they show a lower prevalence when compared to adults. The literature has a relative lack of information about the management and the different treatment protocols regarding these diseases. The aim of this research is to investigate the prevalence of both benign and malignant salivary gland disorders, focusing on diagnostic and therapy. An audit of patients diagnosed with salivary gland disorders was conducted from 2000 to 2020. 99 patients’ records were selected and analyzed: 51 males’ and 48 females’, age 10 ± 4 SD. Obstructive pathologies were the most frequently diagnosed (49 patients) followed by oncologic (21 patients), inflammatory (20 patients), rheumatologic (4 patients), malformative (3 patients) and infective disorders (2 patients). The parotid was the most affected major gland in 47 cases with a prevalence of diagnosis of juvenile recurrent parotitis (JRP) (40.4%), followed by the sublingual gland in 14 cases of ranula (100%) and the submandibular gland in 11 patients suffering from sialolithiasis (84.6%). Swelling was the most common symptom (75.7% of patients). Seven different neoplasms were documented. A greater prevalence of low-grade mucoepidermoid carcinoma among the malignant group (38.1% of oncologic cases) was noted. In regards to benign tumors, pleomorphic adenoma was the most common diagnosis (47.6% of cases). The symptoms and outcomes showed statistical significance concerning gender. Although salivary gland diseases in children and adolescents are rare, it is essential to observe and monitor all of the symptoms to intervene if necessary, as painless swelling is a symptom common from both benign and malignant diseases.
Synthetic Biology of Thermophiles: Taking Bioengineering to the Extremes?
Authors: Vavitsas Konstantinos , Glekas Panayiotis D. , Hatzinikolaou Dimitris G.
Published: February 2022

Synthetic biology applications rely on a well-characterized set of microbial strains, with an established toolbox of molecular biology methods for their genetic manipulation. Since there are no thermophiles with such attributes, most biotechnology and synthetic biology studies use organisms that grow in the mesophilic temperature range. As a result, thermophiles, a heterogenous group of microbes that thrive at high (>50 °C) temperatures, are largely overlooked, with respect to their biotechnological potential, even though they share several favorable traits. Thermophilic bacteria tend to grow at higher rates compared to their mesophilic counterparts, while their growth has lower cooling requirements and is less prone to contamination. Over the last few years, there has been renewed interest in developing tools and methods for thermophile bioengineering. In this perspective, we explain why it is a good idea to invest time and effort into developing a thermophilic synthetic biology direction, which is the state of the art, and why we think that the implementation of a thermophilic synthetic biology platform—a thermochassis—will take synthetic biology to the extremes.
Extending Our Knowledge about the 229Th Nuclear Isomer
Authors: Seiferle Benedict , Moritz Daniel , Scharl Kevin , Ding Shiqian , Zacherl Florian , Löbell Lilli , Thirolf Peter G.
Published: February 2022

The first nuclear excited state in 229Th possesses the lowest excitation energy of all currently known nuclear levels. The energy difference between the ground- and first-excited (isomeric) state (denoted with 229mTh) amounts only to ≈8.2 eV (≈151.2 nm), which results in several interesting consequences: Since the excitation energy is in the same energy range as the binding energy of valence electrons, the lifetime of 229mTh is strongly influenced by the electronic structure of the Th atom or ion. Furthermore, it is possible to potentially excite the isomeric state in 229Th with laser radiation, which led to the proposal of a nuclear clock that could be used to search for new physics beyond the standard model. In this article, we will focus on recent technical developments in our group that will help to better understand the decay mechanisms of 229mTh, focusing primarily on measuring the radiative lifetime of the isomeric state.
Analyzing the Main Determinants for Being an Immigrant in Cuenca (Ecuador) Based on a Fuzzy Clustering Approach
Authors: Martin Juan Carlos , Bustamante-Sánchez Natalia Soledad , Indelicato Alessandro
Published: February 2022

The study aims to analyze the determinants for being an immigrant in Cuenca (Ecuador). Our analysis is based on the answers given to a scale formed by 30 items included in a questionnaire administered to a representative sample of 369 immigrants. A fuzzy hybrid multi-criteria decision-making method, TOPSIS (Technique for Order Preference by Similarity to an Ideal Solution), is used to analyze whether immigrants are more or less exigent regarding the items included in the scale to reside in Cuenca. Then, a fuzzy clustering method is applied to analyze the differences observed in the main determinants observed over a number of traits according to their similarities to three obtained profiles: (1) extreme exigent immigrants; (2) extreme unneedful immigrants; and (3) intermediate exigent immigrants. Results show that items such as access to internet and benefits for retirees were highly valued by some immigrants. In addition, the authors found that information channels, reasons for immigrating, house location, main transport mode, income and main income source are the main determinants that differentiate whether the immigrants in Cuenca (Ecuador) are more or less demanding with respect to the exigency scale developed in the study. The main contributions to the body of knowledge, the policy implications and lines for future research are finally discussed.
g-Expectation for Conformable Backward Stochastic Differential Equations
Authors: Luo Mei , Fečkan Michal , Wang Jin-Rong , O’Regan Donal
Published: February 2022

In this paper, we study the applications of conformable backward stochastic differential equations driven by Brownian motion and compensated random measure in nonlinear expectation. From the comparison theorem, we introduce the concept of g-expectation and give related properties of g-expectation. In addition, we find that the properties of conformable backward stochastic differential equations can be deduced from the properties of the generator g. Finally, we extend the nonlinear Doob–Meyer decomposition theorem to more general cases.
Drosophila melanogaster as a Model Organism for Obesity and Type-2 Diabetes Mellitus by Applying High-Sugar and High-Fat Diets
Authors: Baenas Nieves , Wagner Anika E.
Published: February 2022

Several studies have been published introducing Drosophila melanogaster as a research model to investigate the effects of high-calorie diets on metabolic dysfunctions. However, differences between the use of high-sugar diets (HSD) and high-fat diets (HFD) to affect fly physiology, as well as the influence on sex and age, have been seldom described. Thus, the aim of the present work was to investigate and compare the effects of HSD (30% sucrose) and HFD (15% coconut oil) on symptoms of metabolic dysfunction related to obesity and type-2 diabetes mellitus, including weight gain, survival, climbing ability, glucose and triglycerides accumulation and expression levels of Drosophila insulin-like peptides (dIlps). Female and male flies were subjected to HSD and HFD for 10, 20 and 30 days. The obtained results showed clear differences in the effects of both diets on survival, glucose and triglyceride accumulation and dIlps expression, being gender and age determinant. The present study also suggested that weight gain does not seem to be an appropriate parameter to define fly obesity, since other characteristics appear to be more meaningful in the development of obesity phenotypes. Taken together, the results demonstrate a key role for both diets, HSD and HFD, to induce an obese fly phenotype with associated diseases. However, further studies are needed to elucidate the underlying molecular mechanisms how both diets differently affect fly metabolism.
coupled Hydrodynamic Flow Focusing (cHFF) to Engineer Lipid–Polymer Nanoparticles (LiPoNs) for Multimodal Imaging and Theranostic Applications
Authors: Roffo Felicia , Ponsiglione Alfonso Maria , Netti Paolo Antonio , Torino Enza
Published: February 2022

An optimal design of nanocarriers is required to overcome the gap between synthetic and biological identity, improving the clinical translation of nanomedicine. A new generation of hybrid vehicles based on lipid–polymer coupling, obtained by Microfluidics, is proposed and validated for theranostics and multimodal imaging applications. A coupled Hydrodynamic Flow Focusing (cHFF) is exploited to control the time scales of solvent exchange and the coupling of the polymer nanoprecipitation with the lipid self-assembly simultaneously, guiding the formation of Lipid–Polymer NPs (LiPoNs). This hybrid lipid–polymeric tool is made up of core–shell structure, where a polymeric chitosan core is enveloped in a lipid bilayer, capable of co-encapsulating simultaneously Gd-DTPA and Irinotecan/Atto 633 compounds. As a result, a monodisperse population of hybrid NPs with an average size of 77 nm, with preserved structural integrity in different environmental conditions and high biocompatibility, can be used for MRI and Optical applications. Furthermore, preliminary results show the enhanced delivery and therapeutic efficacy of Irinotecan-loaded hybrid formulation against U87 MG cancers cells.
Shared Molecular Mechanisms among Alzheimer’s Disease, Neurovascular Unit Dysfunction and Vascular Risk Factors: A Narrative Review
Authors: Falsetti Lorenzo , Viticchi Giovanna , Zaccone Vincenzo , Guerrieri Emanuele , Moroncini Gianluca , Luzzi Simona , Silvestrini Mauro
Published: February 2022

Alzheimer’s disease (AD) is the most common type of dementia, affecting 24 million individuals. Clinical and epidemiological studies have found several links between vascular risk factors (VRF), neurovascular unit dysfunction (NVUd), blood-brain barrier breakdown (BBBb) and AD onset and progression in adulthood, suggesting a pathogenetic continuum between AD and vascular dementia. Shared pathways between AD, VRF, and NVUd/BBB have also been found at the molecular level, underlining the strength of this association. The present paper reviewed the literature describing commonly shared molecular pathways between adult-onset AD, VRF, and NVUd/BBBb. Current evidence suggests that VRF and NVUd/BBBb are involved in AD neurovascular and neurodegenerative pathology and share several molecular pathways. This is strongly supportive of the hypothesis that the presence of VRF can at least facilitate AD onset and progression through several mechanisms, including NVUd/BBBb. Moreover, vascular disease and several comorbidities may have a cumulative effect on VRF and worsen the clinical manifestations of AD. Early detection and correction of VRF and vascular disease by improving NVUd/BBBd could be a potential target to reduce the overall incidence and delay cognitive impairment in AD.
Development of Surgically Transplantable Parathyroid Hormone-Releasing Microbeads
Authors: Kim Ha Yeong , Seok Ji Min , Jung Soo Yeon , Lee Min Ji , Tran An Nguyen-Thuy , Yeo Seon Ju , Park Su A. , Kim Han Su
Published: February 2022

Hypoparathyroidism is an endocrine disorder that occurs because of the inability to produce parathyroid hormone (PTH) effectively. Previously, we reported the efficacy of tonsil-derived mesenchymal stem cells (TMSCs) differentiated into parathyroid-like cells for the treatment of hypoparathyroidism. Here, we investigated the feasibility of three-dimensional structural microbeads fabricated with TMSCs and alginate, a natural biodegradable polymer, to treat hypoparathyroidism. Alginate microbeads were fabricated by dropping a 2% (w/v) alginate solution containing TMSCs into a 5% CaCl2 solution and then differentiated into parathyroid-like cells using activin A and sonic hedgehog for 7 days. The protein expression of PTH, a specific marker of the parathyroid gland, was significantly higher in differentiated alginate microbeads with TMSCs (Al-dT) compared with in undifferentiated alginate microbeads with TMSCs. For in vivo experiments, we created the hypoparathyroidism animal model by parathyroidectomy (PTX) and implanted alginate microbeads in the dorsal interscapular region. The PTX rats with Al-dT (PTX+Al-dT) showed the highest survival rate and weight change and a gradual increase in serum intact PTH levels. We also detected a higher expression of PTH in retrieved tissues of PTX+Al-dT using immunofluorescence analysis. This study demonstrates that alginate microbeads are potential a new tool as a surgically scalable therapy for treating hypoparathyroidism.
Highly Sensitive HBsAg, Anti-HBc and Anti HBsAg Titres in Early Diagnosis of HBV Reactivation in Anti-HBc-Positive Onco-Haematological Patients
Authors: Cerva Carlotta , Salpini Romina , Alkhatib Mohammad , Malagnino Vincenzo , Piermatteo Lorenzo , Battisti Arianna , Bertoli Ada , Gersch Jeff , Holzmayer Vera , Kuhns Mary , Cloherty Gavin , Ferrari Ludovica , Laura Campogiani , Teti Elisabetta , Cantonetti Maria , Arcese William , Ceccherini-Silberstein Francesca , Perno Carlo-Federico , Andreoni Massimo , Svicher Valentina , Sarmati Loredana
Published: February 2022

The role of novel HBV markers in predicting Hepatitis B virus reactivation (HBV-R) in HBsAg-negative/anti-HBc-positive oncohaematological patients was examined. One hundred and seven HBsAg-negative/anti-HBc-positive oncohaematological patients, receiving anti-HBV prophylaxis for >18 months, were included. At baseline, all patients had undetectable HBV DNA, and 67.3% were anti-HBs positive. HBV-R occurred in 17 (15.9%) patients: 6 during and 11 after the prophylaxis period. At HBV-R, the median (IQR) HBV-DNA was 44 (27–40509) IU/mL, and the alanine aminotransferase upper limit of normal (ULN) was 44% (median (IQR): 81 (49–541) U/L). An anti-HBc > 3 cut-off index (COI) plus anti-HBs persistently/declining to <50 mIU/mL was predictive for HBV-R (OR (95% CI): 9.1 (2.7–30.2); 63% of patients with vs. 15% without this combination experienced HBV-R (p < 0.001)). The detection of highly sensitive (HS) HBsAg and/or HBV-DNA confirmed at >2 time points, also predicts HBV-R (OR (95% CI): 13.8 (3.6–52.6); 50% of positive vs. 7% of negative patients to these markers experienced HBV-R (p = 0.001)). HS-HBs and anti-HBc titration proved to be useful early markers of HBV-R. The use of these markers demonstrated that HBV-R frequently occurs in oncohaematological patients with signs of resolved HBV infection, raising issues of proper HBV-R monitoring.
A Non-Canonical Link between Non-Coding RNAs and Cardiovascular Diseases
Authors: Natarelli Lucia , Weber Christian
Published: February 2022

Cardiovascular diseases (CVDs) are among the top leading causes of mortality worldwide. Besides canonical environmental and genetic changes reported so far for CVDs, non-coding RNAs (ncRNAs) have emerged as key regulators of genetic and epigenetic mechanisms involved in CVD progression. High-throughput and sequencing data revealed that almost 80% of the total genome not only encodes for canonical ncRNAs, such as micro and long ncRNAs (miRNAs and lncRNAs), but also generates novel non-canonical sub-classes of ncRNAs, such as isomiRs and miRNA- and lncRNA-like RNAs. Moreover, recent studies reveal that canonical ncRNA sequences can influence the onset and evolution of CVD through novel “non-canonical” mechanisms. However, a debate exists over the real existence of these non-canonical ncRNAs and their concrete biochemical functions, with most of the dark genome being considered as “junk RNA”. In this review, we report on the ncRNAs with a scientifically validated canonical and non-canonical biogenesis. Moreover, we report on canonical ncRNAs that play a role in CVD through non-canonical mechanisms of action.
Inflammation and Rho-Associated Protein Kinase-Induced Brain Changes in Vascular Dementia
Authors: Lee Eun Chae , Hong Dong-Yong , Lee Dong-Hun , Park Sang-Won , Lee Ji Young , Jeong Ji Hun , Kim Eun-Young , Chung Hyung-Min , Hong Ki-Sung , Park Se-Pill , Lee Man Ryul , Oh Jae Sang
Published: February 2022

Patients with vascular dementia, caused by cerebral ischemia, experience long-term cognitive impairment due to the lack of effective treatment. The mechanisms of and treatments for vascular dementia have been investigated in various animal models; however, the insufficient information on gene expression changes that define pathological conditions hampers progress. To investigate the underlying mechanism of and facilitate treatment development for vascular dementia, we established a mouse model of chronic cerebral hypoperfusion, including bilateral carotid artery stenosis, by using microcoils, and elucidated the molecular pathway underlying vascular dementia development. Rho-associated protein kinase (ROCK) 1/2, which regulates cellular structure, and inflammatory cytokines (IL-1 and IL-6) were upregulated in the vascular dementia model. However, expression of claudin-5, which maintains the blood–brain barrier, and MAP2 as a nerve cell-specific factor, was decreased in the hippocampal region of the vascular dementia model. Thus, we revealed that ROCK pathway activation loosens the tight junction of the blood–brain barrier and increases the influx of inflammatory cytokines into the hippocampal region, leading to neuronal death and causing cognitive and emotional dysfunction. Our vascular dementia model allows effective study of the vascular dementia mechanism. Moreover, the ROCK pathway may be a target for vascular dementia treatment development in the future.
Examining Association of Personality Characteristics and Neuropsychiatric Symptoms in Post-COVID Syndrome
Authors: Delgado-Alonso Cristina , Valles-Salgado María , Delgado-Álvarez Alfonso , Gómez-Ruiz Natividad , Yus Miguel , Polidura Carmen , Pérez-Izquierdo Carlos , Marcos Alberto , Gil María José , Matías-Guiu Jorge , Matias-Guiu Jordi A.
Published: February 2022

Background: We aimed to evaluate personality traits in patients with post-COVID syndrome, as well as the association with neuropsychiatric symptoms present in this disorder. Methods: The Big Five Structure Inventory was administered to 93 consecutive patients with a diagnosis of post-COVID syndrome as defined by the WHO and to demographically matched controls. We also performed a comprehensive evaluation of depression, anxiety, fatigue, sleep quality, cognitive function, and olfactory function. Results: Patients with post-COVID syndrome scored lower for emotional stability, equanimity, positive mood, and self-control. Extraversion, emotional stability, and openness correlated negatively with anxiety and depression levels. Conscientiousness correlated negatively with anxiety. No statistically significant correlations were observed between personality traits and cognitive function, sleep quality, olfactory function, or fatigue. Personality scores explained 36.3% and 41% of the variance in scores on the anxiety and depression scales, respectively. Two personality profiles with lower levels of emotional stability were associated with depression and anxiety. Conclusions: Our study shows higher levels of neuroticism in patients with post-COVID syndrome. Personality traits were predictive of the presence of depression and anxiety, but not cognitive function, sleep quality, or fatigue, in the context of post-COVID syndrome. These findings may have implications for the detection of patients at risk of depression and anxiety in post-COVID syndrome, and for the development of preventive and therapeutic interventions.
Carbon Composites—Graphene-Oxide-Catalyzed Sugar Graphitization
Authors: Singh Madhu , Vander Wal Randy L.
Published: February 2022

Utilization of biopolymers to form graphitic carbons is challenged by their high oxygen content and resulting curved and defective carbon lamellae upon high-temperature heat-treatment. Two composites, one with graphene-oxide (GO) and the other with reduced graphene-oxide (rGO) as fillers, respectively, in a matrix of sugar, each for the same added 2.5 wt.%, exhibited different degrees of graphitization compared to pure sugar on its own. Reactive oxygen groups on GO contribute to reactive templating and crystallite formation. Under high-temperature heat-treatment, sugar, a well-known non-graphitizing precursor, is converted to graphitic carbon in the presence of GO. Possessing fewer oxygen groups, rGO forms two phases in the sugar matrix—a non-graphitic phase and a graphitic phase. The latter is attributed to the remaining oxygen on the rGO.
Evaluating the Optimal Management of Inoperable Giant Cell Tumors of the Spine: A Systematic Review and Meta-Analysis
Authors: Palmisciano Paolo , Ferini Gianluca , Chen Andrew L. , Balasubramanian Kishore , Kharbat Abdurrahman F. , Sagoo Navraj S. , Bin Alamer Othman , Scalia Gianluca , Umana Giuseppe E. , Aoun Salah G. , Haider Ali S.
Published: February 2022

Background: Surgical resection remains the preferred treatment in spine giant cell tumors (SGCTs), but it is not always feasible. Conservative strategies have been studied for inoperable cases. We systematically reviewed the literature on inoperable SGCTs treated with denosumab, radiotherapy or selective arterial embolization (SAE). Methods: PubMed, Scopus, Web-of-Science, Ovid-EMBASE, and Cochrane were searched following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines to include studies of inoperable SGCTs treated with denosumab, radiotherapy or SAE. Treatment outcomes were analyzed and compared with a random-effect model meta-analysis. Results: Among the 17 studies included, 128 patients received denosumab, 59 radiotherapy, and 43 SAE. No significant differences in baseline patient characteristics were found between the three groups. All strategies were equally effective in providing symptom improvement (p = 0.187, I2 = 0%) and reduction in tumor volume (p = 0.738, I2 = 56.8%). Rates of treatment-related complications were low (denosumab: 12.5%; radiotherapy: 8.5%; SAE: 18.6%) and comparable (p = 0.311, I2 = 0%). Patients receiving denosumab had significantly lower rates of local tumor recurrence (10.9%) and distant metastases (0%) compared to patients receiving radiotherapy (30.5%; 8.5%) or SAE (35.6%; 7%) (p = 0.003, I2 = 32%; p = 0.002, I2 = 47%). Denosumab was also correlated with significantly higher overall survival rates at 18 months (99.2%) and 24 months (99.2%) compared to radiotherapy (91.5%; 89.6%) and SAE (92.5%; 89.4%) (p = 0.019, I2 = 8%; p = 0.004, I2 = 23%). Mortality was higher in patients receiving SAE (20.9%) or radiotherapy (13.6%) compared to denosumab (0.8%) (p < 0.001), but deaths mostly occurred for unrelated diseases. Conclusions: Denosumab, radiotherapy, and SAE are safe and effective for inoperable SGCTs. Clinical and radiological outcomes are mostly comparable, but denosumab may provide superior tumor control.
A Prospective Phase II Study of Automated Non-Coplanar VMAT for Recurrent Head and Neck Cancer: Initial Report of Feasibility, Safety, and Patient-Reported Outcomes
Authors: Woods Kaley E. , Ma Ting Martin , Cook Kiri A. , Morris Eric D. , Gao Yu , Sheng Ke , Kishan Amar U. , Hegde John V. , Felix Carol , Basehart Vincent , Narahara Kelsey , Shen Zhouhuizi , Tenn Stephen , Steinberg Michael L. , Chin Robert K. , Cao Minsong
Published: February 2022

This study reports the initial results for the first 15 patients on a prospective phase II clinical trial exploring the safety, feasibility, and efficacy of the HyperArc technique for recurrent head and neck cancer treatment. Eligible patients were simulated and planned with both conventional VMAT and HyperArc techniques and the plan with superior dosimetry was selected for treatment. Dosimetry, delivery feasibility and safety, treatment-related toxicity, and patient-reported quality of life (QOL) were all evaluated. HyperArc was chosen over conventional VMAT for all 15 patients and enabled statistically significant increases in dose conformity (R50% reduced by 1.2 ± 2.1, p < 0.05) and mean PTV and GTV doses (by 15.7 ± 4.9 Gy, p < 0.01 and 17.1 ± 6.0 Gy, p < 0.01, respectively). The average HyperArc delivery was 2.8 min longer than conventional VMAT (p < 0.01), and the mean intrafraction motion was ≤ 0.5 ± 0.4 mm and ≤0.3 ± 0.1°. With a median follow-up of 12 months, treatment-related toxicity was minimal (only one grade 3 acute toxicity above baseline) and patient-reported QOL metrics were favorable. HyperArc enabled superior dosimetry and significant target dose escalation compared to conventional VMAT planning, and treatment delivery was feasible, safe, and well-tolerated by patients.
The Bright and the Dark Side of TGF-β Signaling in Hepatocellular Carcinoma: Mechanisms, Dysregulation, and Therapeutic Implications
Authors: Gungor Medine Zeynep , Uysal Merve , Senturk Serif
Published: February 2022

Hepatocellular carcinoma (HCC) is associated with genetic and nongenetic aberrations that impact multiple genes and pathways, including the frequently dysregulated transforming growth factor β (TGF-β) signaling pathway. The regulatory cytokine TGF-β and its signaling effectors govern a broad spectrum of spatiotemporally regulated molecular and cellular responses, yet paradoxically have dual and opposing roles in HCC progression. In the early stages of tumorigenesis, TGF-β signaling enforces profound tumor-suppressive effects, primarily by inducing cell cycle arrest, cellular senescence, autophagy, and apoptosis. However, as the tumor advances in malignant progression, TGF-β functionally switches to a pro-tumorigenic signal, eliciting aggressive tumor traits, such as epithelial–mesenchymal transition, tumor microenvironment remodeling, and immune evasion of cancer cells. On this account, the inhibition of TGF-β signaling is recognized as a promising therapeutic strategy for advanced HCC. In this review, we evaluate the functions and mechanisms of TGF-β signaling and relate its complex and pleiotropic biology to HCC pathophysiology, attempting to provide a detailed perspective on the molecular determinants underlying its functional diversion. We also address the therapeutic implications of the dichotomous nature of TGF-β signaling and highlight the rationale for targeting this pathway for HCC treatment, alone or in combination with other agents.
Quantitative Analysis of Radiation-Associated Parenchymal Lung Change
Authors: Chandy Edward , Szmul Adam , Stavropoulou Alkisti , Jacob Joseph , Veiga Catarina , Landau David , Wilson James , Gulliford Sarah , Fenwick John D. , Hawkins Maria A. , Hiley Crispin , McClelland Jamie R.
Published: February 2022

We present a novel classification system of the parenchymal features of radiation-induced lung damage (RILD). We developed a deep learning network to automate the delineation of five classes of parenchymal textures. We quantify the volumetric change in classes after radiotherapy in order to allow detailed, quantitative descriptions of the evolution of lung parenchyma up to 24 months after RT, and correlate these with radiotherapy dose and respiratory outcomes. Diagnostic CTs were available pre-RT, and at 3, 6, 12 and 24 months post-RT, for 46 subjects enrolled in a clinical trial of chemoradiotherapy for non-small cell lung cancer. All 230 CT scans were segmented using our network. The five parenchymal classes showed distinct temporal patterns. Moderate correlation was seen between change in tissue class volume and clinical and dosimetric parameters, e.g., the Pearson correlation coefficient was ≤0.49 between V30 and change in Class 2, and was 0.39 between change in Class 1 and decline in FVC. The effect of the local dose on tissue class revealed a strong dose-dependent relationship. Respiratory function measured by spirometry and MRC dyspnoea scores after radiotherapy correlated with the measured radiological RILD. We demonstrate the potential of using our approach to analyse and understand the morphological and functional evolution of RILD in greater detail than previously possible.
Development of High-Resolution Dedicated PET-Based Radiomics Machine Learning Model to Predict Axillary Lymph Node Status in Early-Stage Breast Cancer
Authors: Cheng Jingyi , Ren Caiyue , Liu Guangyu , Shui Ruohong , Zhang Yingjian , Li Junjie , Shao Zhimin
Published: February 2022

Purpose of the Report: Accurate clinical axillary evaluation plays an important role in the diagnosis and treatment planning for early-stage breast cancer (BC). This study aimed to develop a scalable, non-invasive and robust machine learning model for predicting of the pathological node status using dedicated-PET integrating the clinical characteristics in early-stage BC. Materials and Methods: A total of 420 BC patients confirmed by postoperative pathology were retrospectively analyzed. 18F-fluorodeoxyglucose (18F-FDG) Mammi-PET, ultrasound, physical examination, Lymph-PET, and clinical characteristics were analyzed. The least absolute shrinkage and selection operator (LASSO) regression analysis were used in developing prediction models. The characteristic curve (ROC) of the area under receiver-operator (AUC) and DeLong test were used to evaluate and compare the performance of the models. The clinical utility of the models was determined via decision curve analysis (DCA). Then, a nomogram was developed based on the model with the best predictive efficiency and clinical utility and was validated using the calibration plots. Results: A total of 290 patients were enrolled in this study. The AUC of the integrated model diagnosed performance was 0.94 (95% confidence interval (CI), 0.91–0.97) in the training set (n = 203) and 0.93 (95% CI, 0.88–0.99) in the validation set (n = 87) (both p < 0.05). In clinical N0 subgroup, the negative predictive value reached 96.88%, and in clinical N1 subgroup, the positive predictive value reached 92.73%. Conclusions: The use of a machine learning integrated model can greatly improve the true positive and true negative rate of identifying clinical axillary lymph node status in early-stage BC.
Tumor Accumulation of PIP-Based KRAS Inhibitor KR12 Evaluated by the Use of a Simple, Versatile Chicken Egg Tumor Model
Authors: Higashi Yuya , Ikeda Shuji , Matsumoto Kotaro , Satoh Shinsuke , Komatsu Aoi , Sugiyama Hiroshi , Tamanoi Fuyuhiko
Published: February 2022

Background: The KRAS inhibitor KR12, based on pyrrole-imidazole polyamide (PIP), has been developed and shown to exhibit efficacy in mouse experiments. Because some PIP species exhibit tumor accumulation capability, we decided to evaluate whether the PIP portion of KR12 exhibits tumor accumulation. We employed the CAM assay that provides a simple method for tumor accumulation evaluation. Methods: KR12 PIP was synthesized and conjugated to TAMRA to produce a fluorescently labeled reagent (KR12-TAMRA). This reagent was injected into a fertilized chicken egg that has been transplanted with human cancer cells. Distribution of the red fluorescence was examined by cutting out tumor as well as various organs from the embryo. Results: The red fluorescence of KR12-TAMRA was found to overlap with the green fluorescence of the tumor formed with GFP-expressing cancer cells. We also observed nuclear localization of KR12-TAMRA. Treatment of KR12 that contained the alkylating agent CBI in the tumor-bearing chicken egg resulted in tumor growth inhibition. Conclusions: KR12 contains a PIP that has two key features: tumor accumulation and nuclear localization. KR12 conjugated with CBI exhibits inhibition of tumor growth in the CAM model.
Impact of Open Dialogue about Complementary Alternative Medicine—A Phase II Randomized Controlled Trial
Authors: Stie Mette , Delmar Charlotte , Nørgaard Birgitte , Jensen Lars Henrik
Published: February 2022

Complementary alternative medicine (CAM) may reduce the symptom burden of side effects to antineoplastic treatment but also cause new side effects and non-adherence to conventional treatment. The aim of this RCT was to investigate the impact of open dialogue about complementary alternative medicine (OD-CAM) on cancer patients’ safety, health and quality of life (QoL). Patients undergoing antineoplastic treatment were randomly assigned to standard care (SC) plus OD-CAM or SC alone. The primary endpoint was frequency of grade 3–4 adverse events (AE) eight weeks after enrollment. Secondary endpoints were frequency of grade 1–4 AE, QoL, psychological distress, perceived information, attitude towards and use of CAM 12 and 24 weeks after enrollment. Survival was analyzed post hoc. Fifty-seven patients were randomized to the OD-CAM group and fifty-five to the SC group. No significant difference in frequency of grade 3–4 AEs was shown. The same applied to grade 1–4 AEs and QoL, psychological distress and perceived information. A tendency towards better QoL, improved survival and a lower level of anxiety was found in the OD-CAM group. OD-CAM is not superior to SC in reducing the frequency of AEs in patients undergoing antineoplastic treatment. OD-CAM does not compromise patient safety; it may reduce psychological stress and improve QoL and overall survival.
Chemokine (C-C Motif) Ligand 8 and Tubulo-Interstitial Injury in Chronic Kidney Disease
Authors: Lee Jangwook , Lee Yeonhee , Kim Kyu-Hong , Kim Dong-Ki , Joo Kwon-Wook , Shin Sung-Joon , Kim Yon-Su , Yang Seung-Hee
Published: February 2022

Kidney fibrosis has been accepted to be a common pathological outcome of chronic kidney disease (CKD). We aimed to examine serum levels and tissue expression of chemokine (C-C motif) ligand 8 (CCL8) in patients with CKD and to investigate their association with kidney fibrosis in CKD model. Serum levels and tissue expression of CCL8 significantly increased with advancing CKD stage, proteinuria level, and pathologic deterioration. In Western blot analysis of primary cultured human tubular epithelial cells after induction of fibrosis with rTGF-β, CCL8 was upregulated by rTGF-β treatment and the simultaneous treatment with anti-CCL8 mAb mitigated the rTGF-β-induced an increase in fibronectin and a decrease E-cadherin and BCL-2 protein levels. The antiapoptotic effect of the anti-CCL8 mAb was also demonstrated by Annexin V/propidium iodide staining assay. In qRT-PCR analysis, mRNA expression levels of the markers for fibrosis and apoptosis showed similar expression patterns to those observed by western blotting. The immunohistochemical analysis revealed CCL8 and fibrosis- and apoptosis-related markers significantly increased in the unilateral ureteral obstruction model, which agrees with our in vitro findings. In conclusion, CCL8 pathway is associated with increased risk of kidney fibrosis and that CCL8 blockade can ameliorate kidney fibrosis and apoptosis.
Altered Expression of Zonula occludens-1 Affects Cardiac Na+ Channels and Increases Susceptibility to Ventricular Arrhythmias
Authors: El Refaey Mona , Coles Sara , Musa Hassan , Stevens Tyler L. , Wallace Michael J. , Murphy Nathaniel P. , Antwi-Boasiako Steve , Young Lindsay J. , Manring Heather R. , Curran Jerry , Makara Michael A. , Sas Kelli , Han Mei , Koenig Sara N. , Skaf Michel , Kline Crystal F. , Janssen Paul M. L. , Accornero Federica , Borzok Maegen A. , Mohler Peter J.
Published: February 2022

Zonula occludens-1 (ZO-1) is an intracellular scaffolding protein that orchestrates the anchoring of membrane proteins to the cytoskeleton in epithelial and specialized tissue including the heart. There is clear evidence to support the central role of intracellular auxiliary proteins in arrhythmogenesis and previous studies have found altered ZO-1 expression associated with atrioventricular conduction abnormalities. Here, using human cardiac tissues, we identified all three isoforms of ZO-1, canonical (Transcript Variant 1, TV1), CRA_e (Transcript Variant 4, TV4), and an additionally expressed (Transcript Variant 3, TV3) in non-failing myocardium. To investigate the role of ZO-1 on ventricular arrhythmogenesis, we generated a haploinsufficient ZO-1 mouse model (ZO-1+/−). ZO-1+/− mice exhibited dysregulated connexin-43 protein expression and localization at the intercalated disc. While ZO-1+/− mice did not display abnormal cardiac function at baseline, adrenergic challenge resulted in rhythm abnormalities, including premature ventricular contractions and bigeminy. At baseline, ventricular myocytes from the ZO-1+/− mice displayed prolonged action potential duration and spontaneous depolarizations, with ZO-1+/− cells displaying frequent unsolicited (non-paced) diastolic depolarizations leading to spontaneous activity with multiple early afterdepolarizations (EADs). Mechanistically, ZO-1 deficient myocytes displayed a reduction in sodium current density (INa) and an increased sensitivity to isoproterenol stimulation. Further, ZO-1 deficient myocytes displayed remodeling in ICa current, likely a compensatory change. Taken together, our data suggest that ZO-1 deficiency results in myocardial substrate susceptible to triggered arrhythmias.
Two-Dimensional Dy2O3-Pd-PDA/rGO Heterojunction Nanocomposite: Synergistic Effects of Hybridisation, UV Illumination and Relative Humidity on Hydrogen Gas Sensing
Authors: Hashtroudi Hanie , Yu Aimin , Juodkazis Saulius , Shafiei Mahnaz
Published: February 2022

A two-dimensional (2D) Dy2O3-Pd-PDA/rGO heterojunction nanocomposite has been synthesised and tested for hydrogen (H2) gas sensing under various functioning conditions, including different H2 concentrations (50 ppm up to 6000 ppm), relative humidity (up to 25 %RH) and working temperature (up to 200 °C). The material characterisation of Dy2O3-Pd-PDA/rGO nanocomposite performed using various techniques confirms uniform distribution of Pd NPs and 2D Dy2O3 nanostructures on multi-layered porous structure of PDA/rGO nanosheets (NSs) while forming a nanocomposite. Moreover, fundamental hydrogen sensing mechanisms, including the effect of UV illumination and relative humidity (%RH), are investigated. It is observed that the sensing performance is improved as the operating temperature increases from room temperature (RT = 30 °C) to the optimum temperature of 150 °C. The humidity effect investigation revealed a drastic enhancement in sensing parameters as the %RH increased up to 20%. The highest response was found to be 145.2% towards 5000 ppm H2 at 150 °C and 20 %RH under UV illumination (365 nm). This work offers a highly sensitive and selective hydrogen sensor based on a novel 2D nanocomposite using an environmentally friendly and energy-saving synthesis approach, enabling us to detect hydrogen molecules experimentally down to 50 ppm.
Development of Cyanine 813@Imidazole-Based Doped Supported Devices for Divalent Metal Ions Detection
Authors: Galhano Joana , Marcelo Gonçalo A. , Santos Hugo M. , Capelo-Martínez José Luis , Lodeiro Carlos , Oliveira Elisabete
Published: February 2022

A NIR cyanine@imidazole derivative Cy1 was synthesized and evaluated as a metal ion sensor in solution. Cy1 was shown to be very sensitive to all metal ions tested, presenting a blue shift in the absorption from 668 nm to 633 nm, followed by a change in colour from pale green to blue with Zn2+, Cd2+, Co2+, Ni2+ and Hg2+ ions. Despite the blue shift in the absorption, a decrease at 633 nm (with a colour change from pale green to colourless), as well as a quenching in the emission intensity at 785 nm were observed for Cu2+ ions. The results show the formation of sandwich complexes of two ligands per metal ion with the highest association constant observed for Cu2+ (Log Kass.abs = 14.76 ± 0.09; Log Kass.emis. = 14.79 ± 0.06). The minimal detectable amounts were found to be 31 nM and 37 nM, with a naked eye detection of 2.9 ppm and 2.1 ppm for Hg2+ and Cu2+ ions, respectively. These results prompted us to explore the applicability of Cy1 by its combination with nanomaterials. Thus, Cy1@ doped MNs and Cy1@ doped PMMA nanoparticles were synthesized. Both nanosystems were shown to be very sensitive to Cu2+ ions in water, allowing a naked-eye detection of at least 1 ppm for Cy1@ doped MNs and 7 ppm for Cy1@ doped PMMA. This colourimetric response is an easy and inexpensive way to assess the presence of metals in aqueous media with no need for further instrumentation.
Global Development of Research on Anorectal Malformations over the Last Five Decades: A Bibliometric Analysis
Authors: Martynov Illya , Feng Xiaoyan , Duess Johannes W. , Gosemann Jan-Hendrik , Lacher Martin , Mayer Steffi
Published: February 2022

Purpose: Anorectal malformations (ARM) are one of the most challenging congenital malformations in pediatric surgery. We aimed to assess the research activity on ARM over the last five decades. Methods: Data on original research publications were retrieved from the Web of Science Core Collection (1970–2020), and analyzed for countries, authors, scientific journals, and top-ten papers. Scientific quantity was assessed by the number of publications. Research quality was estimated from the number of citations, average citation rate per item (ACI), and h-index. Results: A total number of 1595 articles with 19,419 citations (ACI = 12.2; h-index = 54) were identified. The annual number of publications and citations significantly increased over time (p < 0.0001). The USA (n = 386; 24.2%), Japan (n = 153; 9.6%), and China (n = 137; 8.6%) were the most productive countries; and the USA (n = 7850; ACI = 20.3; h-index = 44), Japan (n = 1937; ACI = 12.6; h-index = 21), and the Netherlands (n = 1318; ACI = 17.3; h-index = 22) were the top cited countries. Articles were preferentially published in JPS (n = 391; 24.5%), PSI (n = 181; 11.3%), and EJPS (n = 56; 3.5%). Top-ten cited papers focused on classification (n = 1), surgical technique (n = 3), associated syndromes (n = 2), postoperative outcome (n = 3), and basic research (n = 1). Conclusion: This bibliometric study provides valuable insights into the global development of ARM research, and shows that clinical studies and international collaborations dominate in this field.