bluuebunny/crossref_metadata_2025 huggingface dataset:
Artificial Neural Network-Based Model for Prediction of Frost Heave Behavior of Silty Soil Specimen
Authors: Yoon Seok , Le Dinh-Viet , Go Gyu-Hyun
Published: November 2021

Frost heave action is a major issue in permafrost regions that can give rise to various geotechnical engineering problems. To analyze and predict this phenomenon at a specimen scale, this study conducted a fully coupled thermal-hydro-mechanical analysis and evaluated the frost heave behavior of frozen soil considering geotechnical parameters. Furthermore, a parametric study was performed to quantitatively analyze the effects of major geotechnical properties on frost heave behavior. According to the results of the parametric study, the amount of heave tended to decrease as the particle thermal conductivity increased, whereas the frost heave ratio tended to increase as the initial hydraulic conductivity increased. After evaluating the sensitivity of each parameter to frost heave behavior through statistical analyses, an artificial neural network model was developed to practically predict frost heave behavior. According to the verification results of the neural network model, the trained network model demonstrated a reliable accuracy (R2 = 0.893) in predicting frost heave ratio, even when the model used test datasets that were not part of the training datasets.
Group Contribution Revisited: The Enthalpy of Formation of Organic Compounds with “Chemical Accuracy” Part II
Authors: Meier Robert J.
Published: November 2021

Group contribution (GC) methods to predict thermochemical properties are eminently important to process design. We present a group contribution parametrization for the heat of formation of organic molecules exhibiting chemical accuracy, maximum 1 kcal/mol (4.2 kJ/mol) difference between experiment and model values while minimizing the number of parameters avoiding overfitting and therewith avoiding reduced predictability. Compared to the contemporary literature, this was successfully achieved by employing available literature high-quality and consistent experimental data, optimizing parameters group by group, and introducing additional parameters when chemical understanding was obtained supporting these. A further important result is the observation that the applicability of the group contribution approach breaks down with increasing substitution levels, i.e., more heavily alkyl-substituted molecules, the reason being a serious influence of substitution on the conformation of the flexible part of the entire molecule within particular valence angles and torsional angles affected, which cannot be accounted for by additional GC parameters with fixed numerical values.
Bioassay-Guided Identification of Bioactive Compounds from Senna alata L. against Methicillin-Resistant Staphylococcus aureus
Authors: Muhammad Suwaiba Ladan , Wada Yusuf , Mohammed Mustapha , Ibrahim Sani , Musa Kabir Yusuf , Olonitola Olayeni Stephen , Ahmad Mubarak Hussaini , Mustapha Sagir , Abdul Rahman Zaidah , Sha’aban Abubakar
Published: November 2021

Senna alata (Linn) Roxb. plant is widely used to manage various infections in folkloric medicine. Methicillin-resistant Staphylococcus aureus (MRSA) infection continues to be a major global public health problem. This study aims to investigate the bioactive components of S. alata leaves active against MRSA. The leaves of S. alata were sequentially extracted and fractionated using standard methods and screened for activities against MRSA. The diethyl ether active thin layer chromatography (TLC) spot was subjected to infrared (IR) and gas chromatography-mass spectroscopic (GC-MS) studies. The aqueous extract and diethyl ether fraction of S. alata leaves elicited the highest activity against the MRSA. The GC-MS analysis of the fraction produced 15 eluates; only the sub-fraction 13 was effective. The TLC analysis of the sub-fraction 13 revealed three spots; only the second spot produced activity. The GC-MS result of the spot showed six peaks. The spectral results for peak 3 match the data from the IR study, suggestive of 9-octadecenoic acid methyl ester. Senna alata leaves possess bioactive compounds closely related to 9-octadecenoic acid methyl ester with potent antibacterial activity against MRSA.
User eXperience (UX) Evaluation for MR Cultural Applications: The CEMEC Holographic Showcases in European Museums
Authors: Pagano Alfonsina , Pietroni Eva , Ferdani Daniele , d’Annibale Enzo
Published: November 2021

Within the EU CEMEC project framework, a novel approach for using holographic showcases in museums has been conceived and experimented upon in different venues in the context of an itinerant exhibition dealing with Early Medieval European collections. The purpose of this holographic showcase, the so-called “box of stories”, is to improve the link and interaction between real and virtual contents in the museum’s context, making the exhibited object “alive” in the visitors’ perception. An Avar sword and a Byzantine treasure have been used as the main case studies, and they have been experienced in the museums of several European regions by audiences with different cultural backgrounds. This has been a great opportunity to carry out user experience (UX) evaluations in order to collect feedback (from about 600 museum visitors) regarding the attractiveness of such a mixed reality (MR) system, its usability, the comprehension of the contents, the efficacy of the logistics and environmental conditions, as well as the educational impact. The results of such inquiries helped the CNR ISPC team to identify the most meaningful User eXperience Analytics (UXA) able to support the work of UX evaluators and UX designers to assess the efficacy of digital cultural products. Indeed, this manuscript presents UXA and tries to draft a concrete and effective evaluation model for future digital projects for museum contexts.
A Method for Estimating the Cloud Adjacency Effect on the Ground Surface Reflectance Reconstruction from Passive Satellite Observations through Gaps in Cloud Fields
Authors: Tarasenkov Mikhail V. , Zonov Matvei N. , Engel Marina V. , Belov Vladimir V.
Published: November 2021

A method for estimating the cloud adjacency effect on the reflectance of ground surface areas reconstructed from passive satellite observations through gaps in cloud fields is proposed. The method allows one to estimate gaps of cloud fields in which the cloud adjacency effect can be considered small (the increment of the reflectance Δrsurf≤ 0.005). The algorithm is based on statistical simulation by the Monte Carlo method of radiation transfer in stochastic broken cloudiness with a deterministic cylindrical gap. An interpolation formula is obtained for the radius of the cloud adjacency effect that can be used for the reconstruction the ground surface reflectance in real time without calculations by the Monte Carlo method.
Implementation of Battery Digital Twin: Approach, Functionalities and Benefits
Authors: Singh Soumya , Weeber Max , Birke Kai Peter
Published: November 2021

The concept of Digital Twin (DT) is widely explored in literature for different application fields because it promises to reduce design time, enable design and operation optimization, improve after-sales services and reduce overall expenses. While the perceived benefits strongly encourage the use of DT, in the battery industry a consistent implementation approach and quantitative assessment of adapting a battery DT is missing. This paper is a part of an ongoing study that investigates the DT functionalities and quantifies the DT-attributes across the life cycles phases of a battery system. The critical question is whether battery DT is a practical and realistic solution to meeting the growing challenges of the battery industry, such as degradation evaluation, usage optimization, manufacturing inconsistencies or second-life application possibility. Within the scope of this paper, a consistent approach of DT implementation for battery cells is presented, and the main functions of the approach are tested on a Doyle-Fuller-Newman model. In essence, a battery DT can offer improved representation, performance estimation, and behavioral predictions based on real-world data along with the integration of battery life cycle attributes. Hence, this paper identifies the efforts for implementing a battery DT and provides the quantification attribute for future academic or industrial research.
Impact of Vitamin D3 Deficiency on Phosphatidylcholine-/Ethanolamine, Plasmalogen-, Lyso-Phosphatidylcholine-/Ethanolamine, Carnitine- and Triacyl Glyceride-Homeostasis in Neuroblastoma Cells and Murine Brain
Authors: Lauer Anna Andrea , Griebsch Lea Victoria , Pilz Sabrina Melanie , Janitschke Daniel , Theiss Elena Leoni , Reichrath Jörg , Herr Christian , Beisswenger Christoph , Bals Robert , Valencak Teresa Giovanna , Portius Dorothea , Grimm Heike Sabine , Hartmann Tobias , Grimm Marcus Otto Walter
Published: November 2021

Vitamin D3 hypovitaminosis is associated with several neurological diseases such as Alzheimer’s disease, Parkinson’s disease or multiple sclerosis but also with other diseases such as cancer, diabetes or diseases linked to inflammatory processes. Importantly, in all of these diseases lipids have at least a disease modifying effect. Besides its well-known property to modulate gene-expression via the VDR-receptor, less is known if vitamin D hypovitaminosis influences lipid homeostasis and if these potential changes contribute to the pathology of the diseases themselves. Therefore, we analyzed mouse brain with a mild vitamin D hypovitaminosis via a targeted shotgun lipidomic approach, including phosphatidylcholine, plasmalogens, lyso-phosphatidylcholine, (acyl-/acetyl-) carnitines and triglycerides. Alterations were compared with neuroblastoma cells cultivated in the presence and with decreased levels of vitamin D. Both in cell culture and in vivo, decreased vitamin D level resulted in changed lipid levels. While triglycerides were decreased, carnitines were increased under vitamin D hypovitaminosis suggesting an impact of vitamin D on energy metabolism. Additionally, lyso-phosphatidylcholines in particular saturated phosphatidylcholine (e.g., PC aa 48:0) and plasmalogen species (e.g., PC ae 42:0) tended to be increased. Our results suggest that vitamin D hypovitaminosis not only may affect gene expression but also may directly influence cellular lipid homeostasis and affect lipid turnover in disease states that are known for vitamin D hypovitaminosis.
Three-Dimensional Virtual and Printed Prototypes in Complex Congenital and Pediatric Cardiac Surgery—A Multidisciplinary Team-Learning Experience
Authors: Kiraly Laszlo , Shah Nishant C. , Abdullah Osama , Al-Ketan Oraib , Rowshan Reza
Published: November 2021

Three-dimensional (3D) virtual modeling and printing advances individualized medicine and surgery. In congenital cardiac surgery, 3D virtual models and printed prototypes offer advantages of better understanding of complex anatomy, hands-on preoperative surgical planning and emulation, and improved communication within the multidisciplinary team and to patients. We report our single center team-learning experience about the realization and validation of possible clinical benefits of 3D-printed models in surgical planning of complex congenital cardiac surgery. CT-angiography raw data were segmented into 3D-virtual models of the heart-great vessels. Prototypes were 3D-printed as rigid “blood-volume” and flexible “hollow”. The accuracy of the models was evaluated intraoperatively. Production steps were realized in the framework of a clinical/research partnership. We produced 3D prototypes of the heart-great vessels for 15 case scenarios (nine males, median age: 11 months) undergoing complex intracardiac repairs. Parity between 3D models and intraoperative structures was within 1 mm range. Models refined diagnostics in 13/15, provided new anatomic information in 9/15. As a team-learning experience, all complex staged redo-operations (13/15; Aristotle-score mean: 10.64 ± 1.95) were rehearsed on the 3D models preoperatively. 3D-printed prototypes significantly contributed to an improved/alternative operative plan on the surgical approach, modification of intracardiac repair in 13/15. No operative morbidity/mortality occurred. Our clinical/research partnership provided coverage for the extra time/labor and material/machinery not financed by insurance. 3D-printed models provided a team-learning experience and contributed to the safety of complex congenital cardiac surgeries. A clinical/research partnership may open avenues for bioprinting of patient-specific implants.
A Novel Cellular Therapy to Treat Pancreatic Pain in Experimental Chronic Pancreatitis Using Human Alpha-1 Antitrypsin Overexpressing Mesenchymal Stromal Cells
Authors: Chow Rebecca P. , Nguyen Kevin , Gou Wenyu , Green Erica , Morgan Katherine , Lancaster William , Helke Kristi , Strange Charlie , Wang Hongjun
Published: November 2021

Chronic pancreatitis (CP) is characterized by pancreatic inflammation, fibrosis, and abdominal pain that is challenging to treat. Mesenchymal stromal cells (MSCs) overexpressing human alpha-1 antitrypsin (hAAT-MSCs) showed improved mobility and protective functions over native MSCs in nonobese diabetic mice. We investigated whether hAAT-MSCs could mitigate CP and its associated pain using trinitrobenzene sulfonic acid (TNBS)-induced CP mouse models. CP mice were given native human MSCs or hAAT-MSCs (0.5 × 106 cells/mouse, i.v., n = 6–8/group). The index of visceral pain was measured by graduated von Frey filaments. Pancreatic morphology and pancreatic mast cell count were analyzed by morphological stains. Nociceptor transient receptor potential vanilloid 1 (TRPV1) expression in dorsal root ganglia (DRG) was determined by immunohistochemistry. hAAT-MSC-treated CP mice best preserved pancreatic morphology and histology. MSC or hAAT-MSC infusion reduced abdominal pain sensitivities. hAAT-MSC therapy also suppressed TRPV1 expression in DRG and reduced pancreatic mast cell density induced by TNBS. Overall, hAAT-MSCs reduced pain and mitigated pancreatic inflammation in CP equal to MSCs with a trend toward a higher pancreatic weight and better pain relief in the hAAT-MSC group compared to the MSC group. Both MSCs and hAAT-MSCs might be used as a novel therapeutic tool for CP-related pain.
Bisphosphonates for the Treatment of Calcinosis Cutis—A Retrospective Single-Center Study
Authors: Rauch Lilian , Hein Rüdiger , Biedermann Tilo , Eyerich Kilian , Lauffer Felix
Published: November 2021

(1) Background: Calcinosis cutis is a frequent symptom of autoimmune connective tissue diseases leading to pain, transcutaneous expulsion of calcified material and bacterial superinfection. There is a high need for new therapeutic options as no standardized treatment algorithm is established. While case reports indicate beneficial effects of bisphosphonates, standardized evaluation of treatment effects is missing. (2) Methods: In this retrospective analysis we evaluate the effects of intravenous pamidronate, a second-generation bisphosphonate, in seven patients with calcinosis cutis using consecutive clinical pictures, radiological examinations and patient’s subjective evaluation. (3) Results: 5/6 patients reported a reduction of pain, improvement of general condition and cessation of calcinosis progression. Regression of skin lesions was detectable in clinical pictures of 2/6 patients, while 1/6 patients had stable disease. Radiological examination revealed improvement or stable disease in 3/5 patients. Fever was the most common side effect. One out of seven patients developed osteonecrosis of the jaw. (4) Conclusions: Bisphosphonates appear to have beneficial effects in a subgroup of calcinosis cutis patients. While patient’s subjective evaluation was mainly positive, objective assessments showed improvement in approximately half of the cases. With regard to potential severe side effects, a careful risk-benefit evaluation is necessary before treatment initiation.
Microfluidic-Chip-Integrated Biosensors for Lung Disease Models
Authors: Ding Shuang , Zhang Haijun , Wang Xuemei
Published: November 2021

Lung diseases (e.g., infection, asthma, cancer, and pulmonary fibrosis) represent serious threats to human health all over the world. Conventional two-dimensional (2D) cell models and animal models cannot mimic the human-specific properties of the lungs. In the past decade, human organ-on-a-chip (OOC) platforms—including lung-on-a-chip (LOC)—have emerged rapidly, with the ability to reproduce the in vivo features of organs or tissues based on their three-dimensional (3D) structures. Furthermore, the integration of biosensors in the chip allows researchers to monitor various parameters related to disease development and drug efficacy. In this review, we illustrate the biosensor-based LOC modeling, further discussing the future challenges as well as perspectives in integrating biosensors in OOC platforms.
Real-World Outcomes of Glucose Sensor Use in Type 1 Diabetes—Findings from a Large UK Centre
Authors: Lee Kyuhan , Gunasinghe Shakthi , Chapman Alyson , Findlow Lynne A. , Hyland Jody , Ohol Sheetal , Urwin Andrea , Rutter Martin K. , Schofield Jonathan , Thabit Hood , Leelarathna Lalantha
Published: November 2021

Flash glucose monitoring (FGM) and real-time continuous glucose monitoring (RT-CGM) are increasingly used in clinical practice, with improvements in HbA1c and time in range (TIR) reported in clinical studies. We aimed to evaluate the impact of FGM and RT-CGM use on glycaemic outcomes in adults with type 1 diabetes (T1DM) under routine clinical care. We performed a retrospective data analysis from electronic outpatient records and proprietary web-based glucose monitoring platforms. We measured HbA1c (pre-sensor vs. on-sensor data) and sensor-based outcomes from the previous three months as per the international consensus on RT-CGM reporting guidelines. Amongst the 789 adults with T1DM, HbA1c level decreased from 61.0 (54.0, 71.0) mmol/mol to 57 (49, 65.8) mmol/mol in 561 people using FGM, and from 60.0 (50.0, 70.0) mmol/mol to 58.8 (50.3, 66.8) mmol/mol in 198 using RT-CGM (p < 0.001 for both). We found that 23% of FGM users and 32% of RT-CGM users achieved a time-in-range (TIR) (3.9 to 10 mmol/L) of >70%. For time-below-range (TBR) < 4 mmol/L, 70% of RT-CGM users and 58% of FGM users met international recommendations of <4%. Our data add to the growing body of evidence supporting the use of FGM and RT-CGM in T1DM.
Electrochemical Biosensor for Markers of Neurological Esterase Inhibition
Authors: Rafat Neda , Satoh Paul , Worden Robert Mark
Published: November 2021

A novel, integrated experimental and modeling framework was applied to an inhibition-based bi-enzyme (IBE) electrochemical biosensor to detect acetylcholinesterase (AChE) inhibitors that may trigger neurological diseases. The biosensor was fabricated by co-immobilizing AChE and tyrosinase (Tyr) on the gold working electrode of a screen-printed electrode (SPE) array. The reaction chemistry included a redox-recycle amplification mechanism to improve the biosensor’s current output and sensitivity. A mechanistic mathematical model of the biosensor was used to simulate key diffusion and reaction steps, including diffusion of AChE’s reactant (phenylacetate) and inhibitor, the reaction kinetics of the two enzymes, and electrochemical reaction kinetics at the SPE’s working electrode. The model was validated by showing that it could reproduce a steady-state biosensor current as a function of the inhibitor (PMSF) concentration and unsteady-state dynamics of the biosensor current following the addition of a reactant (phenylacetate) and inhibitor phenylmethylsulfonylfluoride). The model’s utility for characterizing and optimizing biosensor performance was then demonstrated. It was used to calculate the sensitivity of the biosensor’s current output and the redox-recycle amplification factor as a function of experimental variables. It was used to calculate dimensionless Damkohler numbers and current-control coefficients that indicated the degree to which individual diffusion and reaction steps limited the biosensor’s output current. Finally, the model’s utility in designing IBE biosensors and operating conditions that achieve specific performance criteria was discussed.
Evaluation of the Effectiveness of a Soil Treatment Using Calcium Carbonate Precipitation from Cultivated and Lyophilized Bacteria in Soil’s Compaction Water
Authors: Valencia-Galindo Miguel , Sáez Esteban , Ovalle Carlos , Ruz Francisco
Published: November 2021

Microbial-induced carbonate precipitation (MICP) is a bio-inspired solution where bacteria metabolize urea to precipitate. This carbonate acts as a bio-cement that bonds soil particles. The existing framework has focused mainly on applying MICP through infiltration of liquid bacterial solutions in existing soil deposits. However, this technique is inefficient in soils with high fines content and low hydraulic conductivity, and thus few studies have focused on the use of MICP in fine soils. The main objective of this study was to evaluate the effect of MICP applied to compaction water in soils containing expansive clays and sandy silts. This approach searches for a better distribution of bacteria, nutrients, and calcium sources and is easy to apply if associated with a compaction process. In soils with expansive minerals, the effect of MICP in swelling potential was explored at laboratory and field scales. In sandy silts, the evolution of the stiffness and strength were studied at the laboratory scale. The treatment at the laboratory scale reduced the swelling potential; nevertheless, no significant effect of MICP was found in the field test. In sandy silts, the strength and stiffness increased under unsaturated conditions; however, subsequent saturation dissolved the cementation and the improvement vanished.
Visualizing a New Sustainable World: Toward the Next Generation of Virtual Reality in the Built Environment
Authors: Nikolić Dragana , Whyte Jennifer
Published: November 2021

What is the future of virtual reality (VR) in the built environment? As work becomes increasingly distributed across remote and hybrid forms of organizing as a result of the COVID-19 pandemic, there is a need to rethink how we use the set of collaborative technologies to move toward a sustainable world. We propose a new vision of VR as a discipline-agnostic platform for an interdisciplinary integration of the allied design, social, and environmental disciplines to address emerging challenges across the building sectors. We build this contribution through the following steps. First, we contextualize VR technologies within the changing digital landscape and underlying tensions in the built environment practices. Second, we characterize the difficulties that have arisen in using them to address challenges, illustrating our argument with leading examples. Third, we conceptualize VR configurations and explore underlying assumptions for their use across disciplinary scenarios. Fourth, we propose a vision of VR as a discipline-agnostic platform that can support built environment users in visualizing preferred futures. We conclude by providing directions for research and practice.
Pareto-Based Bi-Objective Optimization Method of Sensor Placement in Structural Health Monitoring
Authors: Nong Shao-Xiao , Yang Dong-Hui , Yi Ting-Hua
Published: November 2021

For a practical structural health monitoring (SHM) system, the traditional single objective methods for optimal sensor placement (OSP) cannot always obtain the optimal result of sensor deployment without sacrificing other targets, which creates obstacles to the efficient use of the sensors. This study mainly focuses on establishing a bi-objective optimization method to select the sensor placement positions. The practical significance of several single-objective criteria for OSP is firstly discussed, based on which a novel bi-objective optimization method is proposed based on the Pareto optimization process, and the corresponding objective functions are established. Furthermore, the non-dominated sorting genetic algorithm is introduced to obtain a series of the Pareto optimal solutions, from which the final solution can be determined based on a new defined membership degree index. Finally, a numerical example of a plane truss is applied to illustrate the proposed method. The Pareto optimization-based bi-objective OSP framework presented in this study could be well suited for solving the problem of multi-objective OSP, which can effectively improve the efficiency of the limited sensors in SHM system.
Recent Research on Combination of Radiotherapy with Targeted Therapy or Immunotherapy in Head and Neck Squamous Cell Carcinoma: A Review for Radiation Oncologists
Authors: Xing Daniel Tao , Khor Richard , Gan Hui , Wada Morikatsu , Ermongkonchai Tai , Ng Sweet Ping
Published: November 2021

Radiotherapy plays an important role of managing head and neck squamous cell carcinoma (HNSCC). Concurrent radiotherapy with radiosensitizing cisplastin chemotherapy is the standard of care (SOC) for non-operable locally advanced HNSCC. Cetuximab, a monoclonal antibody of epidermal growth factor receptor, was the most extensively studied targeted therapy as a chemo-sparing agent that was used concurrently with radiotherapy. Immunotherapy is used in the treatment of metastatic HNSCC. There is evidence to support the synergistic effect when combining radiotherapy with immunotherapy to potentiate anti-tumor immune response. There has been increasing interest to incorporate immune checkpoint inhibitor (ICI) with radiotherapy in the curative setting for HNSCC. In this review, we discuss the latest evidence that supports concurrent radiotherapy with cisplatin which remains the SOC for locally advanced HNSCC (LA-HNSCC). Cetuximab is suitable for patients who are not fit for cisplatin. We then summarize the clinical trials that incorporate ICI with radiotherapy for LA-HNSCC in concurrent, neoadjuvant, and adjuvant settings. We also discuss the potential of combining immunotherapy with radiotherapy as a treatment de-escalating strategy in HPV-associated oropharyngeal carcinoma. Finally, the pre-clinical and clinical evidence of the abscopal effect when combining stereotactic body radiotherapy with ICIs is presented.
Geriatric Oncology: From Research to Clinical Practice
Authors: de Glas Nienke A.
Published: November 2021

The incidence of cancer in older adults is strongly increasing due to the ageing of the population [...]
Changes in Blood Biomarkers of Angiogenesis and Immune Modulation after Radiation Therapy and Their Association with Outcomes in Thoracic Malignancies
Authors: Gkika Eleni , Adebahr Sonja , Brenner Anton , Schimek-Jasch Tanja , Radicioni Gianluca , Exner Jan-Philipp , Rühle Alexander , Spohn Simon K. B. , Popp Ilinca , Zamboglou Constantinos , Sprave Tanja , Firat Elke , Niedermann Gabriele , Nicolay Nils Henrik , Nestle Ursula , Grosu Anca-Ligia , Duda Dan G.
Published: November 2021

The effects of radiotherapy on systemic immunity remain to be fully characterized in a disease-specific manner. The aim of the study was to examine potential biomarkers of systemic immunomodulation when using radiotherapy for thoracic malignancies. Serial blood samples were collected from 56 patients with thoracic malignancies prior (RTbaseline), during (RTduring) and at the end of radiotherapy (RTend), as well as at the first (FU1) and second follow-up (FU2). The changes in serum levels of IL-10, IFN-γ, IL-12p70, IL-13, IL-1β, IL-4, IL-6, IL-8, TNF-α, bFGF, sFlt-1, PlGF, VEGF, VEGF-C, VEGF-D and HGF were measured by multiplexed array and tested for associations with clinical outcomes. We observed an increase in the levels of IL-10, IFN-γ, PlGF and VEGF-D and a decrease in those of IL-8, VEGF, VEGF-C and sFlt-1 during and at the end of radiotherapy. Furthermore, baseline concentration of TNF-α significantly correlated with OS. IL-6 level at RTend and FU1,2 correlated with OS (RTend: p = 0.039, HR: 1.041, 95% CI: 1.002–1.082, FU1: p = 0.001, HR: 1.139, 95% CI: 1.056–1.228, FU2: p = 0.017, HR: 1.101 95% CI: 1.018–1.192), while IL-8 level correlated with OS at RTduring and RTend (RTduring: p = 0.017, HR: 1.014, 95% CI: 1.002–1.026, RTend: p = 0.004, HR: 1.007, 95% CI: 1.061–1.686). In conclusion, serum levels of TNF-α, IL-6 and IL-8 are potential biomarkers of response to radiotherapy. Given the recent implementation of immunotherapy in lung and esophageal cancer, these putative blood biomarkers should be further validated and evaluated in the combination or sequential therapy setting.
Effects of Aerobic Exercise Training on MyomiRs Expression in Cachectic and Non-Cachectic Cancer Mice
Authors: Gomes João Lucas Penteado , Tobias Gabriel Cardial , Fernandes Tiago , Silveira André Casanova , Negrão Carlos Eduardo , Chammas Roger , Brum Patrícia Chakur , Oliveira Edilamar Menezes
Published: November 2021

We investigated the effects of AET on myomiRs expression in the skeletal muscle and serum of colon cachectic (CT26) and breast non-cachectic (MMTV-PyMT) cancer mice models. Colon cancer decreased microRNA-486 expression, increasing PTEN in tibialis anterior muscle (TA), decreasing the PI3K/mTOR protein pathway, body and muscle wasting, fibers’ cross-sectional area and muscle dysfunction, that were not preserved by AET. In contrast, breast cancer decreased those muscle functions, but were preserved by AET. In circulation, the downregulation of microRNA-486 and -206 in colon cancer, and the downregulation of microRNA-486 and upregulation of microRNA-206 expression in breast cancer might be good cancer serum biomarkers. Since the microRNA-206 is skeletal muscle specific, their expression was increased in the TA, serum and tumor in MMTV, suggesting a communication among these three compartments. The AET prevents these effects on microRNA-206, but not on microRNA-486 in MMTV. In conclusion, cancer induced a downregulation of microRNA-486 expression in TA and serum of CT26 and MMTV mice and these effects were not prevented by AET; however, to MMTV, the trained muscle function was preserved, probably sustained by the downregulation of microRNA-206 expression. Serum microRNA-206 is a potential biomarker for colon (decreased) and breast (increased) cancer to monitor the disease evolution and the effects promoted by the AET.
Targeting Tie2 in the Tumor Microenvironment: From Angiogenesis to Dissemination
Authors: Duran Camille L. , Borriello Lucia , Karagiannis George S. , Entenberg David , Oktay Maja H. , Condeelis John S.
Published: November 2021

The Tie2 receptor tyrosine kinase is expressed in vascular endothelial cells, tumor-associated macrophages, and tumor cells and has been a major focus of research in therapies targeting the tumor microenvironment. The most extensively studied Tie2 ligands are Angiopoietin 1 and 2 (Ang1, Ang2). Ang1 plays a critical role in vessel maturation, endothelial cell migration, and survival. Ang2, depending on the context, may function to disrupt connections between the endothelial cells and perivascular cells, promoting vascular regression. However, in the presence of VEGF-A, Ang2 instead promotes angiogenesis. Tie2-expressing macrophages play a critical role in both tumor angiogenesis and the dissemination of tumor cells from the primary tumor to secondary sites. Therefore, Ang-Tie2 signaling functions as an angiogenic switch during tumor progression and metastasis. Here we review the recent advances and complexities of targeting Tie2 signaling in the tumor microenvironment as a possible anti-angiogenic, and anti-metastatic, therapy and describe its use in combination with chemotherapy.
Quantitative Imaging Biomarkers of the Whole Liver Tumor Burden Improve Survival Prediction in Metastatic Pancreatic Cancer
Authors: Gebauer Leonie , Moltz Jan H. , Mühlberg Alexander , Holch Julian W. , Huber Thomas , Enke Johanna , Jäger Nils , Haas Michael , Kruger Stephan , Boeck Stefan , Sühling Michael , Katzmann Alexander , Hahn Horst , Kunz Wolfgang G. , Heinemann Volker , Nörenberg Dominik , Maurus Stefan
Published: November 2021

Finding prognostic biomarkers with high accuracy in patients with pancreatic cancer (PC) remains a challenging problem. To improve the prediction of survival and to investigate the relevance of quantitative imaging biomarkers (QIB) we combined QIB with established clinical parameters. In this retrospective study a total of 75 patients with metastatic PC and liver metastases were analyzed. Segmentations of whole liver tumor burden (WLTB) from baseline contrast-enhanced CT images were used to derive QIBs. The benefits of QIBs in multivariable Cox models were analyzed in comparison with two clinical prognostic models from the literature. To discriminate survival, the two clinical models had concordance indices of 0.61 and 0.62 in a statistical setting. Combined clinical and imaging-based models achieved concordance indices of 0.74 and 0.70 with WLTB volume, tumor burden score (TBS), and bilobar disease being the three WLTB parameters that were kept by backward elimination. These combined clinical and imaging-based models have significantly higher predictive performance in discriminating survival than the underlying clinical models alone (p < 0.003). Radiomics and geometric WLTB analysis of patients with metastatic PC with liver metastases enhances the modeling of survival compared with models based on clinical parameters alone.
Relationship between Tumor Mutational Burden, PD-L1, Patient Characteristics, and Response to Immune Checkpoint Inhibitors in Head and Neck Squamous Cell Carcinoma
Authors: Burcher Kimberly M. , Lantz Jeffrey W. , Gavrila Elena , Abreu Arianne , Burcher Jack T. , Faucheux Andrew T. , Xie Amy , Jackson Clayton , Song Alexander H. , Hughes Ryan T. , Lycan Thomas , Bunch Paul M. , Furdui Cristina M. , Topaloglu Umit , D’Agostino Ralph B. , Zhang Wei , Porosnicu Mercedes
Published: November 2021

Failure to predict response to immunotherapy (IO) limited its benefit in the treatment of head and neck squamous cell cancer (HNSCC) to 20% of patients or less. Biomarkers including tumor mutational burden (TMB) and programmed death ligand-1 (PD-L1) were evaluated as predictors of response to IO, but the results are inconsistent and with a lack of standardization of their methods. In this retrospective study, TMB and PD-L1 were measured by commercially available methodologies and were correlated to demographics, outcome, and response to PD-1 inhibitors. No correlation was found between TMB and PD-L1 levels. High TMB was associated with smoking and laryngeal primaries. PD-L1 was significantly higher in African Americans, patients with earlier stage tumors, nonsmokers, and nonethanol drinkers. Patients with high TMB fared better in univariate and multivariate survival analysis. No correlation was found between PD-L1 expression and prognosis. There was a statistically significant association between PFS and response to IO and TMB. There was no association between response to ICI and PD-L1 in this study, possibly affected by variations in the reporting method. Further studies are needed to characterize the biomarkers for IO in HNSCC, and this study supports further research into the advancement of TMB in prospective studies.
Can Naloxegol Therapy Improve Quality of Life in Patients with Advanced Cancer?
Authors: Ostan Rita , Gambino Giuseppe , Malavasi Italo , Ronga Gianluca , Solipaca Maria , Spunghi Michela , Varani Silvia , Pannuti Raffaella , Ruggeri Enrico
Published: November 2021

This observational study aims to evaluate the efficacy of naloxegol therapy in resolving opioid-induced constipation (OIC) and in improving the quality of life in a home palliative care cancer setting. Advanced cancer patients with OIC (Rome IV criteria) not relieved by laxatives started a naloxegol therapy 25 mg/day for 4 weeks. Quality of life was evaluated by Patient Assessment of Constipation Quality-of-Life (PAC-QoL) at day 0 and day 28; background pain by Numerical Rating Scale, number of weekly spontaneous bowel movements and Bowel Function Index (BFI) were evaluated at day 0 and every week. Seventy-eight patients who completed the 4-week study improved all four PAC-QoL dimensions (physical and psychological discomfort, worries/concerns and satisfaction level). Weekly spontaneous bowel movements increased and BFI improved. Background pain reduced after seven days and remained lower during the following weeks. Seventy-two patients dropped out the study before day 28 with a reduced survival compared to patients completing the study. Even in these patients, an improvement of bowel function was observed after two weeks. Naloxegol was effective in improving the quality of life, resolving OIC and reducing overall pain in patients with advanced cancer.
Correlation of Soluble CD44 Expression in Saliva and CD44 Protein in Oral Leukoplakia Tissues
Authors: Čēma Ingrīda , Dzudzilo Madara , Kleina Regīna , Franckevica Ivanda , Svirskis Šimons
Published: November 2021

The aim of this study was to determine whether and how pan-CD44 protein expression in leukoplakia tissues correlates with positive SolCD44 test presence and their role in oral leukoplakia. SolCD44 and total protein expression in saliva were determined using an OncAlert® Oral Cancer Rapid test. Comparison of paired associations of total protein, SolCD44, mean number of CD44 expressed epithelial layers in leukoplakia tissue, and macrophages below the basement membrane between control group and patients with leukoplakia showed statistically significant results (p < 0.0001). It is shown that the total protein indicates low or elevated risk of possible malignant transformation processes in leukoplakia. Statistically significant differences between higher total protein level and clinical forms of oral leukoplakia (p < 0.0001), as well as CD44-labeled epithelial cell layer decrease (p < 0.0001), were found. This possibly points to the onset of the stemness loss in leukoplakia tissue. CD9 antigen expression in the exosomes of the oral epithelium explained the intercellular flow of SolCD44 and other fluids in the leukoplakia area. We conclude that the OncAlert® Oral Cancer Rapid test is a valuable screening method in daily clinical practice, in terms of complementing clinical diagnostics methods and to assess the potential for early malignancy.
Copper-Catalyzed Synthesis of Coumarins. A Mini-Review
Authors: Dalpozzo Renato , Mancuso Raffaella
Published: November 2021

Coumarin (2H-chromen-2-one) derivatives have important uses in medicinal and synthetic chemistry, for example, as fluorescent probes. These properties have prompted chemists to develop efficient synthetic methods to synthesize the coumarin core and/or to functionalize it. In this context, many metal-catalyzed syntheses of coumarins have been introduced; among them, copper-catalyzed reactions appear to be very promising owing to the non-toxicity and cheapness of copper complexes. In this mini-review, the results in this field are summarized. We hope to stimulate other applications of these complexes in the preparation of coumarin derivatives.
Dynamic 3D On-Chip BBB Model Design, Development, and Applications in Neurological Diseases
Authors: Chen Xingchi , Liu Chang , Muok Laureana , Zeng Changchun , Li Yan
Published: November 2021

The blood–brain barrier (BBB) is a vital structure for maintaining homeostasis between the blood and the brain in the central nervous system (CNS). Biomolecule exchange, ion balance, nutrition delivery, and toxic molecule prevention rely on the normal function of the BBB. The dysfunction and the dysregulation of the BBB leads to the progression of neurological disorders and neurodegeneration. Therefore, in vitro BBB models can facilitate the investigation for proper therapies. As the demand increases, it is urgent to develop a more efficient and more physiologically relevant BBB model. In this review, the development of the microfluidics platform for the applications in neuroscience is summarized. This article focuses on the characterizations of in vitro BBB models derived from human stem cells and discusses the development of various types of in vitro models. The microfluidics-based system and BBB-on-chip models should provide a better platform for high-throughput drug-screening and targeted delivery.
A Review on the Evolving Roles of MiRNA-Based Technologies in Diagnosing and Treating Heart Failure
Authors: Kennel Peter J. , Schulze P. Christian
Published: November 2021

MiRNA-regulated processes are pivotal in cardiovascular homeostasis and disease. These short non-coding RNAs have ideal properties that could be utilized as potential biomarkers; moreover, their functions as post-transcriptional regulators of mRNA make them interesting therapeutic targets. In this review, we summarize the current state of miRNA-based biomarkers in a variety of diseases leading to heart failure, as well as provide an outlook on developing miRNA-based therapies in the heart failure field.
Cell Cycle, Telomeres, and Telomerase in Leishmania spp.: What Do We Know So Far?
Authors: Assis Luiz H. C. , Andrade-Silva Débora , Shiburah Mark E. , de Oliveira Beatriz C. D. , Paiva Stephany C. , Abuchery Bryan E. , Ferri Yete G. , Fontes Veronica S. , de Oliveira Leilane S. , da Silva Marcelo S. , Cano Maria Isabel N.
Published: November 2021

Leishmaniases belong to the inglorious group of neglected tropical diseases, presenting different degrees of manifestations severity. It is caused by the transmission of more than 20 species of parasites of the Leishmania genus. Nevertheless, the disease remains on the priority list for developing new treatments, since it affects millions in a vast geographical area, especially low-income people. Molecular biology studies are pioneers in parasitic research with the aim of discovering potential targets for drug development. Among them are the telomeres, DNA–protein structures that play an important role in the long term in cell cycle/survival. Telomeres are the physical ends of eukaryotic chromosomes. Due to their multiple interactions with different proteins that confer a likewise complex dynamic, they have emerged as objects of interest in many medical studies, including studies on leishmaniases. This review aims to gather information and elucidate what we know about the phenomena behind Leishmania spp. telomere maintenance and how it impacts the parasite’s cell cycle.
Microfluidic Simulation and Optimization of Blood Coagulation Factors and Anticoagulants in Polymethyl Methacrylate Microchannels
Authors: Immanuel Philip Nathaniel , Chiu Yi-Hsiung , Huang Song-Jeng
Published: November 2021

Blood coagulation is a critical and complex reaction that involves various chemical substances, such as prothrombin, fibrinogen, and fibrin. The process can be divided into three main steps, namely the formation of the prothrombin activator, conversion of prothrombin to thrombin, and conversion of fibrinogen to fibrin. In this study, an ANSYS simulation is carried out to determine the prothrombin time (PT) of blood, the chemical changes that occur during coagulation and the anticoagulation factor. The addition of deionized water to the microchannels before the addition of blood and reagents results in a two-phase flow. The evaluation of this two-phase flow is necessary, and dynamic simulations are required to determine the PT. The chemical rate constant and order of the chemical reaction are derived from the actual prothrombin time. Moreover, the genetic algorithms in PYTHON and ANSYS are used to estimate chemical reaction parameters for a 20 s PT. The blood and anticoagulant exhibit increased dynamic behavior in the microchannel. In addition, particles are added to the microchannel and the dynamic mesh method is used to simulate the flow behaviors of the red and white blood cells in the microchannel. The PTs for different volumes of blood are also reported.
Modern Software for Computer Modeling in Quantum Chemistry and Molecular Dynamics
Authors: Malyshkina Marina V. , Novikov Alexander S.
Published: November 2021

The most popular modern programs for quantum chemical and molecular dynamics (classical, ab initio, and QM/MM) calculations, which are relevant for the investigation of nature and various properties of different molecules and periodic chemical systems such as nanotubes, surfaces and films, polymers, and crystalline solids, are highlighted and briefly discussed.
Collagen-Binding Nanoparticles: A Scoping Review of Methods and Outcomes
Authors: Roată Cristian-Ene , Iacob Ștefan , Morărașu Ștefan , Livadaru Cristian , Tudorancea Ionuț , Luncă Sorinel , Dimofte Mihail-Gabriel
Published: November 2021

(1) Background: Collagen is the main component of the connective tissue, playing an important role in the histological architecture and function of living organisms. Targeted therapy and improved imaging diagnosis can be obtained through collagen-binding nanoparticles that concentrate in the extracellular matrix. (2) Methods: We performed a scoping review of studies that analyzed the binding capacity of collagen-targeting nanoparticles. The search algorithm and inclusion criteria were based on PRISMA and ARRIVE guidelines. (3) Results: Fourteen studies matched all the inclusion criteria. All studies analyzed the distribution of nanoparticles in the collagen matrix, either by using collagen-targeting nanoparticles or by using unmodified ones. Most studies used collagen-binding nanoparticles for vascular research to target sites of endothelial injury, atherosclerotic plaques, or myocardial infarction. Two studies targeted the exposed collagen in models of liver fibrosis. (4) Conclusions: Our review summarizes the current literature on the methods and outcomes of using nanoparticles to target collagen. The studies reveal that there is high applicability for collagen-binding nanoparticles in cardiac or hepatic pathology and they could prove useful for targeted therapy of neoplastic lesions, which show an abundance of stromal collagen.
Abstracts of the 113th Annual Meeting of the Swiss Neurological Society, Congress Centre Kursaal Interlaken, Switzerland, November 18–19, 2021
Authors: Jung Hans , Fischer Urs
Published: November 2021

On behalf of Swiss Neurological Society together with the Swiss Society for Behavioral Neurology, we are pleased to present the Abstracts of the 113th Annual Meeting, which was held from 18–19 November 2021. Fifteen (15) abstracts were selected for oral presentations and sixty-one (61) abstracts were selected as poster presentations. We congratulate all the presenters on their research work and contribution.
Cutaneous Malignancies in Tattoos, a Case Series of Six Patients
Authors: Leijs Marike , Schaefer Hannah , Rübben Albert , Cacchi Claudio , Rustemeyer Thomas , van der Bent Sebastiaan
Published: November 2021

Background: A variety of side effects following the tattooing of the skin were reported over the years. Analytical studies showed that some tattoo inks contain harmful compounds. Methods: We presented six patient cases with cutaneous malignancies in tattooed skin and performed an extensive literature research. Results: Two patients with black ink tattoos that were diagnosed with malignant melanoma raises the number of described cases to 36 patients. One of the patients developed an immunologic reaction limited to the tattoo area after treatment with a targeted immune therapy. In the other patient, the malignancy (malignant melanoma) was fatal. Basal cell carcinoma was seen in four patients with tattoos containing varying ink colors (black, green, red). This increased the number of described patient cases to 18. Although some ink components and their cleavage products have carcinogenic properties, epidemiological evidence for a causative correlation fails. Further epidemiologic studies on tattoos and malignancies, as well as on the appearance of naevi in tattoos, are necessary. Determining the type of mutation might be helpful to separate sun-induced tumors from skin cancers due to other pathogenic mechanisms.