bluuebunny/crossref_metadata_2025 huggingface dataset:
Reliability Analysis of C4ISR Systems Based on Goal-Oriented Methodology
Authors: Li Yifan , Huang Hong-Zhong , Zhang Tingyu
Published: July 2021

Hard-and-software integrated systems such as command and control systems (C4ISR systems) are typical systems that are comprised of both software and hardware, the failures of such devices result from complicated common cause failures and common (or shared) signals that make classical reliability analysis methods will be not applicable. To this end, this paper applies the Goal-Oriented (GO) methodology to detailed analyze the reliability of a C4ISR system. The reliability as well as the failure probability of the C4ISR system, are reached based on the GO model constructed. At the component level, the reliability of units of the C4ISR system is computed. Importance analysis of failures of such a system is completed by the qualitative analysis capability of the GO model, by which critical failures of hardware failures like communication module failures and motherboard module failures as well as software failures like network module application software failures and decompression module software failures are ascertained. This method of this paper contributes to the reliability analysis of all hard-and-software integrated systems.
A Study on Visually Induced VR Reduction Method for Virtual Reality Sickness
Authors: Won Ju-hye , Kim Yoon Sang
Published: July 2021

In this paper, we propose a new type of visually induced reduction method for virtual reality (VR) sickness. This method induces a gaze based on a visual guide (VG). Although VGs are used in commercial VR game contents as crosshairs, no studies have been conducted related to VR sickness. VGs can have various properties determined by position, size, shape, color, etc., and it was necessary to investigate which properties affect VR sickness. In particular, size and position of VG are properties that directly affect the user’s gaze movement. Therefore, in this paper, five VR sickness reduction methods with different position and size of VG are proposed. Then, an experiment was conducted to investigate the effectiveness of the proposed VR sickness reduction method. To this end, a SSQ (including nausea, oculomotor discomfort, disorientation, and total score) and a questionnaire on fatigue and immersion were used. From the experimental results, a VG with a size 30% that of the aspect ratio, and a position synchronized to the user’s head movement direction, was most effective in terms of VR sickness reduction and immersion.
Interview: Acclaimed Game Designer Ryan Kaufman Discusses Telltale Games, Star Wars, Harry Potter, and How Video Games Can Transform Us
Authors: Thomas Christian
Published: July 2021

Ryan Kaufman—whose rich body of work often centers on video games adapted from movies or TV shows—has had a profound impact on video game designers, writers, and players alike [...]
Large-Eddy Simulation of Plume Dispersion in the Central District of Oklahoma City by Coupling with a Mesoscale Meteorological Simulation Model and Observation
Authors: Nakayama Hiromasa , Takemi Tetsuya , Yoshida Toshiya
Published: July 2021

Contaminant gas dispersion within an urban area resulting from accidental or intentional release is of great concern to public health and social security. When estimating plume dispersion in a built-up urban area under real meteorological conditions by computational fluid dynamics (CFD), a crucial issue is how to prescribe the input conditions. There are typically two approaches: using the outputs of a mesoscale meteorological simulation (MMS) model and meteorological observations (OBS). However, the influences of the different approaches on the simulation results have not been fully demonstrated. In this study, we conducted large-eddy simulations (LESs) of plume dispersion in the urban central district of Oklahoma City under real meteorological conditions by coupling with a MMS model and OBS obtained at a single stationary point, and evaluated the two different coupling simulations in comparison with the field experiments. The LES–MMS coupling showed better performance than the LES–OBS one. The latter one also showed a reasonable performance comparable to the acceptance criteria on the model prediction within a factor of two of the experimental data. These facts indicate that the approach using observations at a single stationary point still has enough potential to drive CFD models for plume dispersion under real meteorological conditions.
A Graphics Processing Unit (GPU) Approach to Large Eddy Simulation (LES) for Transport and Contaminant Dispersion
Authors: Bieringer Paul E. , Piña Aaron J. , Lorenzetti David M. , Jonker Harmen J. J. , Sohn Michael D. , Annunzio Andrew J. , Fry Richard N.
Published: July 2021

Recent advances in the development of large eddy simulation (LES) atmospheric models with corresponding atmospheric transport and dispersion (AT&D) modeling capabilities have made it possible to simulate short, time-averaged, single realizations of pollutant dispersion at the spatial and temporal resolution necessary for common atmospheric dispersion needs, such as designing air sampling networks, assessing pollutant sensor system performance, and characterizing the impact of airborne materials on human health. The high computational burden required to form an ensemble of single-realization dispersion solutions using an LES and coupled AT&D model has, until recently, limited its use to a few proof-of-concept studies. An example of an LES model that can meet the temporal and spatial resolution and computational requirements of these applications is the joint outdoor-indoor urban large eddy simulation (JOULES). A key enabling element within JOULES is the computationally efficient graphics processing unit (GPU)-based LES, which is on the order of 150 times faster than if the LES contaminant dispersion simulations were executed on a central processing unit (CPU) computing platform. JOULES is capable of resolving the turbulence components at a suitable scale for both open terrain and urban landscapes, e.g., owing to varying environmental conditions and a diverse building topology. In this paper, we describe the JOULES modeling system, prior efforts to validate the accuracy of its meteorological simulations, and current results from an evaluation that uses ensembles of dispersion solutions for unstable, neutral, and stable static stability conditions in an open terrain environment.
A Review of Metal Levels in Urban Dust, Their Methods of Determination, and Risk Assessment
Authors: Kaonga Chikumbusko Chiziwa , Kosamu Ishmael Bobby Mphangwe , Utembe Wells Robert
Published: July 2021

This review gives insights into the levels of metals in urban dust, their determination methods, and risk assessment. Urban dust harbors a number of pollutants, including heavy metals. There are various methods used for the sampling of urban dust for heavy-metal analysis and source-apportionment purposes, with the predominant one being the use of plastic sampling materials to avoid prior contamination. There are also various methods for the determination of metals, which include: atomic absorption spectroscopy (AAS) and inductively coupled plasma-mass spectrometry (ICP-MS), among others. Studies have shown that pollutants in urban dust are mainly derived from industrial activities and coal combustion, whereas traffic emissions are also an important, but not a predominant source of pollution. The varying particle-size distribution of urban dust and its large surface area makes it easier for the deposition and transport of heavy metals. Risk-assessment studies have shown that metals in urban dust could cause such problems as human pulmonary toxicity and reduction of invertebrate populations. The risk levels seem to be higher in children than adults, as some studies have shown. It is therefore important that studies on metals in urban dust should always incorporate risk assessment as one of the main issues.
Distinguished Property in Tensor Products and Weak* Dual Spaces
Authors: López-Alfonso Salvador , López-Pellicer Manuel , Moll-López Santiago
Published: July 2021

A local convex space E is said to be distinguished if its strong dual Eβ′ has the topology β(E′,(Eβ′)′), i.e., if Eβ′ is barrelled. The distinguished property of the local convex space CpX of real-valued functions on a Tychonoff space X, equipped with the pointwise topology on X, has recently aroused great interest among analysts and Cp-theorists, obtaining very interesting properties and nice characterizations. For instance, it has recently been obtained that a space CpX is distinguished if and only if any function f∈RX belongs to the pointwise closure of a pointwise bounded set in CX. The extensively studied distinguished properties in the injective tensor products CpX⊗εE and in Cp(X,E) contrasts with the few distinguished properties of injective tensor products related to the dual space LpX of CpX endowed with the weak* topology, as well as to the weak* dual of Cp(X,E). To partially fill this gap, some distinguished properties in the injective tensor product space LpX⊗εE are presented and a characterization of the distinguished property of the weak* dual of Cp(X,E) for wide classes of spaces X and E is provided.
Monoamine Oxidase Inhibition by Major Tanshinones from Salvia miltiorrhiza and Selective Muscarinic Acetylcholine M4 Receptor Antagonism by Tanshinone I
Authors: Prajapati Ritu , Park Se Eun , Seong Su Hui , Paudel Pradeep , Fauzi Fazlin Mohd , Jung Hyun Ah , Choi Jae Sue
Published: July 2021

Monoamine oxidases (MAOs) and muscarinic acetylcholine receptors (mAChRs) are considered important therapeutic targets for Parkinson’s disease (PD). Lipophilic tanshinones are major phytoconstituents in the dried roots of Salvia miltiorrhiza that have demonstrated neuroprotective effects against dopaminergic neurotoxins and the inhibition of MAO-A. Since MAO-B inhibition is considered an effective therapeutic strategy for PD, we tested the inhibitory activities of three abundant tanshinone congeners against recombinant human MAO (hMAO) isoenzymes through in vitro experiments. In our study, tanshinone I (1) exhibited the highest potency against hMAO-A, followed by tanshinone IIA and cryptotanshinone, with an IC50 less than 10 µM. They also suppressed hMAO-B activity, with an IC50 below 25 µM. Although tanshinones are known to inhibit hMAO-A, their enzyme inhibition mechanism and binding sites have yet to be investigated. Enzyme kinetics and molecular docking studies have revealed the mode of inhibition and interactions of tanshinones during enzyme inhibition. Proteochemometric modeling predicted mAChRs as possible pharmacological targets of 1, and in vitro functional assays confirmed the selective M4 antagonist nature of 1 (56.1% ± 2.40% inhibition of control agonist response at 100 µM). These findings indicate that 1 is a potential therapeutic molecule for managing the motor dysfunction and depression associated with PD.
Omalizumab Restores Response to Corticosteroids in Patients with Eosinophilic Chronic Rhinosinusitis and Severe Asthma
Authors: Kobayashi Yoshiki , Kanda Akira , Bui Dan Van , Yun Yasutaka , Nguyen Linh Manh , Chu Hanh Hong , Mitani Akitoshi , Suzuki Kensuke , Asako Mikiya , Iwai Hiroshi
Published: July 2021

Eosinophilic chronic rhinosinusitis (ECRS), which is a subgroup of chronic rhinosinusitis with nasal polyps, is characterized by eosinophilic airway inflammation extending across both the upper and lower airways. Some severe cases are refractory even after endoscopic sinus surgery, likely because of local steroid insensitivity. Although real-life studies indicate that treatment with omalizumab for severe allergic asthma improves the outcome of coexistent ECRS, the underlying mechanisms of omalizumab in eosinophilic airway inflammation have not been fully elucidated. Twenty-five patients with ECRS and severe asthma who were refractory to conventional treatments and who received omalizumab were evaluated. Nineteen of twenty-five patients were responsive to omalizumab according to physician-assessed global evaluation of treatment effectiveness. In the responders, the levels of peripheral blood eosinophils and fractionated exhaled nitric oxide (a marker of eosinophilic inflammation) and of CCL4 and soluble CD69 (markers of eosinophil activation) were reduced concomitantly with the restoration of corticosteroid sensitivity. Omalizumab restored the eosinophil-peroxidase-mediated PP2A inactivation and steroid insensitivity in BEAS-2B. In addition, the local inflammation simulant model using BEAS-2B cells incubated with diluted serum from each patient confirmed omalizumab’s effects on restoration of corticosteroid sensitivity via PP2A activation; thus, omalizumab could be a promising therapeutic option for refractory eosinophilic airway inflammation with corticosteroid resistance.
Comparative Study of In Situ Techniques to Enlarge Gold Nanoparticles for Highly Sensitive Lateral Flow Immunoassay of SARS-CoV-2
Authors: Panferov Vasily G. , Byzova Nadezhda A. , Biketov Sergey F. , Zherdev Anatoly V. , Dzantiev Boris B.
Published: July 2021

Three techniques were compared for lowering the limit of detection (LOD) of the lateral flow immunoassay (LFIA) of the receptor-binding domain of severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) based on the post-assay in situ enlargement of Au nanoparticles (Au NPs) on a test strip. Silver enhancement (growth of a silver layer over Au NPs—Au@Ag NPs) and gold enhancement (growth of a gold layer over Au NPs) techniques and the novel technique of galvanic replacement of Ag by Au in Au@Ag NPs causing the formation of Au@Ag-Au NPs were performed. All the enhancements were performed on-site after completion of the conventional LFIA and maintained equipment-free assay. The assays demonstrated lowering of LODs in the following rows: 488 pg/mL (conventional LFIA with Au NPs), 61 pg/mL (silver enhancement), 8 pg/mL (galvanic replacement), and 1 pg/mL (gold enhancement). Using gold enhancement as the optimal technique, the maximal dilution of inactivated SARS-CoV-2-containing samples increased 500 times. The developed LFIA provided highly sensitive and rapid (8 min) point-of-need testing.
A Gabor Filter-Based Protocol for Automated Image-Based Building Detection
Authors: Munawar Hafiz Suliman , Aggarwal Riya , Qadir Zakria , Khan Sara Imran , Kouzani Abbas Z. , Mahmud M. A. Parvez
Published: July 2021

Detecting buildings from high-resolution satellite imagery is beneficial in mapping, environmental preparation, disaster management, military planning, urban planning and research purposes. Differentiating buildings from the images is possible however, it may be a time-consuming or complicated process. Therefore, the high-resolution imagery from satellites needs to be automated to detect the buildings. Additionally, buildings exhibit several different characteristics, and their appearance in these images is unplanned. Moreover, buildings in the metropolitan environment are typically crowded and complicated. Therefore, it is challenging to identify the building and hard to locate them. To resolve this situation, a novel probabilistic method has been suggested using local features and probabilistic approaches. A local feature extraction technique was implemented, which was used to calculate the probability density function. The locations in the image were represented as joint probability distributions and were used to estimate their probability distribution function (pdf). The density of building locations in the image was extracted. Kernel density distribution was also used to find the density flow for different metropolitan cities such as Sydney (Australia), Tokyo (Japan), and Mumbai (India), which is useful for distribution intensity and pattern of facility point f interest (POI). The purpose system can detect buildings/rooftops and to test our system, we choose some crops with panchromatic high-resolution satellite images from Australia and our results looks promising with high efficiency and minimal computational time for feature extraction. We were able to detect buildings with shadows and building without shadows in 0.4468 (seconds) and 0.5126 (seconds) respectively.
Supply Chain Responsiveness to a (Post)-Pandemic Grocery and Food Service E-Commerce Economy: An Exploratory Canadian Case Study
Authors: Charlebois Sylvain , Juhasz Mark , Music Janet
Published: July 2021

The focus of this study looks at the motivations and rationale from a national survey of over 7200 Canadians in November 2020 into why they use online services to purchase food. As a result of the global COVID-19 pandemic, food supply chains have been significantly altered. Consumers are purchasing foods with different dynamics, including when they buy in-person at groceries, at restaurants or at food service establishments. Elements of the food supply chain will be permanently altered post-pandemic. The study looks at a specific set of factors, captured in the survey, namely, consumer price sensitivity to the costs of online food purchasing, growing sustainability-related concerns over food packaging and waste, and product sensory experience related to how online purchasing changes from in-person food selection. The end goal, emerging from a case study, is insight into the strategies and preparedness with which CPGs, food services, and retailers can better manage the supply chain in their food product offerings in the post-pandemic era.
Maintaining Weight Loss in Obese Men with Prostate Cancer Following a Supervised Exercise and Nutrition Program—A Pilot Study
Authors: Wilson Rebekah L. , Taaffe Dennis R. , Newton Robert U. , Hart Nicolas H. , Lyons-Wall Philippa , Galvão Daniel A.
Published: July 2021

Supervised exercise and nutrition programs can mitigate or reverse androgen deprivation therapy (ADT) induced fat mass (FM) gain, lean mass (LM) loss, and impaired physical function. It is unclear whether these benefits are retained following transition to self-management. This study examined the effect of a home-based weight maintenance program on body composition and physical function in obese men with prostate cancer (PCa) on ADT following a 12-week supervised weight loss intervention. Eleven obese PCa patients (74 ± 5 years, 40.0 ± 4.9% body fat) on ADT (>6 months) completed a 12-week self-managed home-based weight maintenance program consisting of 150 min/week of aerobic and resistance training while maintaining a healthy balanced diet. Body composition (DXA), muscle strength (1RM), and cardiorespiratory fitness (400 m walk) were assessed. Significant reductions in weight (−2.8 ± 3.2 kg) and FM (−2.8 ± 2.6 kg), preservation of LM (−0.05 ± 1.6 kg), and improvements in muscle strength and VO2max were achieved across the supervised intervention. Across the home-based program, no significant changes were observed in weight (−0.6 ± 2.8 kg, p = 0.508), FM (0.2 ± 1.4 kg, p = 0.619), LM (−0.8 ± 1.6 kg, p = 0.146), muscle strength (−0.2 to 4.1%, p = 0.086–0.745), or estimated VO2max (0.3 ± 2.1 mL/min/kg, p = 0.649). Self-managed, home-based exercise and nutrition programs are a viable strategy to promote maintenance of body composition and physical function following a supervised intervention in obese PCa patients on ADT.
Three-Dimensional Culture Models to Study Innate Anti-Tumor Immune Response: Advantages and Disadvantages
Authors: Poggi Alessandro , Villa Federico , Fernadez Jordi Leonardo Castrillo , Costa Delfina , Zocchi Maria Raffaella , Benelli Roberto
Published: July 2021

Several approaches have shown that the immune response against tumors strongly affects patients’ clinical outcome. Thus, the study of anti-tumor immunity is critical to understand and potentiate the mechanisms underlying the elimination of tumor cells. Natural killer (NK) cells are members of innate immunity and represent powerful anti-tumor effectors, able to eliminate tumor cells without a previous sensitization. Thus, the study of their involvement in anti-tumor responses is critical for clinical translation. This analysis has been performed in vitro, co-incubating NK with tumor cells and quantifying the cytotoxic activity of NK cells. In vivo confirmation has been applied to overcome the limits of in vitro testing, however, the innate immunity of mice and humans is different, leading to discrepancies. Different activating receptors on NK cells and counter-ligands on tumor cells are involved in the antitumor response, and innate immunity is strictly dependent on the specific microenvironment where it takes place. Thus, three-dimensional (3D) culture systems, where NK and tumor cells can interact in a tissue-like architecture, have been created. For example, tumor cell spheroids and primary organoids derived from several tumor types, have been used so far to analyze innate immune response, replacing animal models. Herein, we briefly introduce NK cells and analyze and discuss in detail the properties of 3D tumor culture systems and their use for the study of tumor cell interactions with NK cells.
Large-Scale Transcriptomics-Driven Approach Revealed Overexpression of CRNDE as a Poor Survival Prognosis Biomarker in Glioblastoma
Authors: Sorokin Maxim , Raevskiy Mikhail , Zottel Alja , Šamec Neja , Skoblar Vidmar Marija , Matjašič Alenka , Zupan Andrej , Mlakar Jernej , Suntsova Maria , Kuzmin Denis V. , Buzdin Anton , Jovčevska Ivana
Published: July 2021

Glioblastoma is the most common and malignant brain malignancy worldwide, with a 10-year survival of only 0.7%. Aggressive multimodal treatment is not enough to increase life expectancy and provide good quality of life for glioblastoma patients. In addition, despite decades of research, there are no established biomarkers for early disease diagnosis and monitoring of patient response to treatment. High throughput sequencing technologies allow for the identification of unique molecules from large clinically annotated datasets. Thus, the aim of our study was to identify significant molecular changes between short- and long-term glioblastoma survivors by transcriptome RNA sequencing profiling, followed by differential pathway-activation-level analysis. We used data from the publicly available repositories The Cancer Genome Atlas (TCGA; number of annotated cases = 135) and Chinese Glioma Genome Atlas (CGGA; number of annotated cases = 218), and experimental clinically annotated glioblastoma tissue samples from the Institute of Pathology, Faculty of Medicine in Ljubljana corresponding to 2–58 months overall survival (n = 16). We found one differential gene for long noncoding RNA CRNDE whose overexpression showed correlation to poor patient OS. Moreover, we identified overlapping sets of congruently regulated differential genes involved in cell growth, division, and migration, structure and dynamics of extracellular matrix, DNA methylation, and regulation through noncoding RNAs. Gene ontology analysis can provide additional information about the function of protein- and nonprotein-coding genes of interest and the processes in which they are involved. In the future, this can shape the design of more targeted therapeutic approaches.
The Prognostic Value of CD206 in Solid Malignancies: A Systematic Review and Meta-Analysis
Authors: Debacker Jens M. , Gondry Odrade , Lahoutte Tony , Keyaerts Marleen , Huvenne Wouter
Published: July 2021

An increased presence of CD206-expressing tumor associated macrophages in solid cancers was proposed to be associated with worse outcomes in multiple types of malignancies, but contradictory results are published. We performed a reproducible systematic review and meta-analysis to provide increased evidence to confirm or reject this hypothesis following the Preferred Reporting Items for Systematic Reviews and Meta-analyses statement. The Embase, Web of Science, and MEDLINE-databases were systematically searched for eligible manuscripts. A total of 27 papers studying the prognostic impact of CD206 in 14 different tumor types were identified. Meta-analyses showed a significant impact on the overall survival (OS) and disease-free survival (DFS). While no significant differences were revealed in progression-free survival (PFS) and disease-specific survival (DSS), a shift towards negative survival was correlated with increased CD206-expresion. As a result of the different tumor types, large heterogeneity was present between the different tumor types. Subgroup analysis of hepatocellular carcinoma and gastric cancers revealed no heterogeneity, associated with a significant negative impact on OS in both groups. The current systematic review displays the increased presence CD206-expressing macrophages as a significant negative prognostic biomarker for both OS and DFS in patients diagnosed with solid cancers. Because a heterogenous group of tumor types was included in the meta-analysis, the results cannot be generalized. These results can, however, be used to further lead follow-up research to validate the specific prognostic value of CD206 in individual tumor types and therapeutic approaches.
Association of Physical Activity with the Risk of Hepatocellular Carcinoma in Patients with Chronic Hepatitis B
Authors: Chun Ho Soo , Park Sojeong , Lee Minjong , Cho Yuri , Kim Ha Sung , Choe A Reum , Kim Hwi Young , Yoo Kwon , Kim Tae Hun
Published: July 2021

Background and Aims: In the general population, previous studies reported that physical activity was associated with risk of hepatocellular carcinoma (HCC) development. However, it is unclear whether physical activity is associated with risk of HCC development in patients with chronic hepatitis B (CHB). We aimed to elucidate the association between physical activity and risk of HCC development in CHB patients. Methods: This nationwide cohort study involved treatment-naive patients with CHB (n = 9727) who started treatment with entecavir or tenofovir and answered self-reported questionnaires between January 2012 and December 2017, using data from the Korean National Health Insurance Service database. The primary endpoint was development of HCC. Multivariable Cox regression and competing risk analyses were used. Results: During a median follow-up of 3.1 years, cumulative HCC incidence rates were 8.3%. There was an inverse association between physical activity and the risk of HCC (p < 0.001). Patients with 1000–1500 metabolic equivalent task (MET)-min/week, compared to those without physical activity, showed a significantly lower risk of HCC in both patients without cirrhosis (adjusted hazard ratio [aHR] 0.66, p = 0.02) and patients with cirrhosis (aHR 0.61, p = 0.02). In patients who were younger (<60), male, without diabetes, and with high BMI, amounts of physical activity of 1000–1500 MET-min/week showed an inverse association with the risk of HCC (aHR 0.65, 0.63, 0.65, and 0.64, respectively, all p < 0.05). Conclusion: Physical activity was significantly associated with a low risk of HCC in CHB patients treated with entecavir or tenofovir.
Is Hypoxia a Factor Influencing PSMA-Directed Radioligand Therapy?—An In Silico Study on the Role of Chronic Hypoxia in Prostate Cancer
Authors: Birindelli Gabriele , Drobnjakovic Milos , Morath Volker , Steiger Katja , D’Alessandria Calogero , Gourni Eleni , Afshar-Oromieh Ali , Weber Wolfgang , Rominger Axel , Eiber Matthias , Shi Kuangyu
Published: July 2021

Radioligand therapy (RLT) targeting prostate specific-membrane antigen (PSMA) is an emerging treatment for metastatic castration-resistant prostate cancer (mCRPC). It administrates 225Ac- or 177Lu-labeled ligands for the targeted killing of tumor cells. Differently from X- or γ-ray, for the emitted α or β particles the ionization of the DNA molecule is less dependent on the tissue oxygenation status. Furthermore, the diffusion range of electrons in a tumor is much larger than the volume typically spanned by hypoxic regions. Therefore, hypoxia is less investigated as an influential factor for PSMA-directed RLT, in particular with β emitters. This study proposes an in silico approach to theoretically investigate the influence of tumor hypoxia on the PSMA-directed RLT. Based on mice histology images, the distribution of the radiopharmaceuticals was simulated with an in silico PBPK-based convection–reaction–diffusion model. Three anti-CD31 immunohistochemistry slices were used to simulate the tumor microenvironment. Ten regions of interest with varying hypoxia severity were analyzed. A kernel-based method was developed for dose calculation. The cell survival probability was calculated according to the linear-quadratic model. The statistical analysis performed on all the regions of interest (ROIs) shows more heterogeneous dose distributions obtained with 225Ac compared to 177Lu. The higher homogeneity of 177Lu-PSMA-ligand treatment is due to the larger range covered by the emitted β particles. The dose-to-tissue histogram (DTH) metric shows that in poorly vascularized ROIs only 10% of radiobiological hypoxic tissue receives the target dose using 177Lu-PSMA-ligand treatment. This percentage drops down to 5% using 225Ac. In highly vascularized ROIs, the percentage of hypoxic tissue receiving the target dose increases to more than 85% and 65% for the 177Lu and 225Ac-PSMA-ligands, respectively. The in silico study demonstrated that the reduced vascularization of the tumor strongly influences the dose delivered by PSMA-directed RLT, especially in hypoxic regions and consequently the treatment outcome.
Micro- and Mycobiota Dysbiosis in Pancreatic Ductal Adenocarcinoma Development
Authors: Bellotti Ruben , Speth Cornelia , Adolph Timon E. , Lass-Flörl Cornelia , Effenberger Maria , Öfner Dietmar , Maglione Manuel
Published: July 2021

Background: Dysbiosis of the intestinal flora has emerged as an oncogenic contributor in different malignancies. Recent findings suggest a crucial tumor-promoting role of micro- and mycobiome alterations also in the development of pancreatic ductal adenocarcinoma (PDAC). Methods: To summarize the current knowledge about this topic, a systematic literature search of articles published until October 2020 was performed in MEDLINE (PubMed). Results: An increasing number of publications describe associations between bacterial and fungal species and PDAC development. Despite the high inter-individual variability of the commensal flora, some studies identify specific microbial signatures in PDAC patients, including oral commensals like Porphyromonas gingivalis and Fusobacterium nucleatum or Gram-negative bacteria like Proteobacteria. The role of Helicobacter spp. remains unclear. Recent isolation of Malassezia globosa from PDAC tissue suggest also the mycobiota as a crucial player of tumorigenesis. Based on described molecular mechanisms and interactions between the pancreatic tissue and the immune system this review proposes a model of how the micro- and the mycobial dysbiosis could contribute to tumorigenesis in PDAC. Conclusions: The presence of micro- and mycobial dysbiosis in pancreatic tumor tissue opens a fascinating perspective on PDAC oncogenesis. Further studies will pave the way for novel tumor markers and treatment strategies.
Characterization of Novel Progression Factors in Castration-Resistant Prostate Cancer Based on Global Comparative Proteome Analysis
Authors: Na Ann-Yae , Choi Soyoung , Yang Eunju , Liu Kwang-Hyeon , Kim Sunghwan , Jung Hyun Jin , Choe Youngshik , Ha Yun-Sok , Kwon Tae Gyun , Lee Jun Nyung , Lee Sangkyu
Published: July 2021

Identifying the biological change from hormone-naïve prostate cancer to castration-resistant prostate cancer (CRPC) is a major clinical challenge for developing therapeutic agents. Although the pathways that lead to CRPC are not fully completely understood, recent evidence demonstrates that androgen signaling is often maintained through varied mechanisms. Androgen deprivation therapy (ADT) is used as a primary treatment for preventing the progression of prostate cancer (PCa). Here we investigated PCa tissues at each stage of progression, from benign prostatic hyperplasia (BPH) to CRPC, based on quantitative proteomic technology, including tissues after ADT. In total, 4768 proteins were identified in this study, of which 4069 were quantified in the combined PCa tissues. Among the quantified proteins, 865 were differentially expressed proteins (21.2%). Based on the quantitative protein results, we performed systematic bioinformatics analysis and found that the levels of 15 proteins, including FOXA1 and HMGN1–3, increased among T3G3, T3GX, and CRPC, despite the ADT. Among all targets, we verified the increased levels of FOXA1 and HMGN1–3 in CRPC by immunoblotting and indirect enzyme-linked immunosorbent assay. In summary, we discuss the changes in intracellular factors involved in the progression of CRPC PCa despite ADT. Moreover, we suggest that FOXA1 and HMGN1–3 proteins could be used as potential CRPC-related factors in clinical therapeutic agents.
Cardiolipin, Non-Bilayer Structures and Mitochondrial Bioenergetics: Relevance to Cardiovascular Disease
Authors: Gasanoff Edward S. , Yaguzhinsky Lev S. , Garab Győző
Published: July 2021

The present review is an attempt to conceptualize a contemporary understanding about the roles that cardiolipin, a mitochondrial specific conical phospholipid, and non-bilayer structures, predominantly found in the inner mitochondrial membrane (IMM), play in mitochondrial bioenergetics. This review outlines the link between changes in mitochondrial cardiolipin concentration and changes in mitochondrial bioenergetics, including changes in the IMM curvature and surface area, cristae density and architecture, efficiency of electron transport chain (ETC), interaction of ETC proteins, oligomerization of respiratory complexes, and mitochondrial ATP production. A relationship between cardiolipin decline in IMM and mitochondrial dysfunction leading to various diseases, including cardiovascular diseases, is thoroughly presented. Particular attention is paid to the targeting of cardiolipin by Szeto–Schiller tetrapeptides, which leads to rejuvenation of important mitochondrial activities in dysfunctional and aging mitochondria. The role of cardiolipin in triggering non-bilayer structures and the functional roles of non-bilayer structures in energy-converting membranes are reviewed. The latest studies on non-bilayer structures induced by cobra venom peptides are examined in model and mitochondrial membranes, including studies on how non-bilayer structures modulate mitochondrial activities. A mechanism by which non-bilayer compartments are formed in the apex of cristae and by which non-bilayer compartments facilitate ATP synthase dimerization and ATP production is also presented.
ACE2 Is Expressed in Immune Cells That Infiltrate the Placenta in Infection-Associated Preterm Birth
Authors: Lye Phetcharawan , Dunk Caroline E. , Zhang Jianhong , Wei Yanxing , Nakpu Jittanan , Hamada Hirotaka , Imperio Guinever E. , Bloise Enrrico , Matthews Stephen G. , Lye Stephen J.
Published: July 2021

COVID-19 is associated with increased incidence of preterm birth (PTB). We assessed pathways by which SARS-CoV-2 could access the placenta. Placentae, from PTB with or without chorioamnionitis (ChA), or from term pregnancies (n = 12/13/group) were collected. Peripheral blood was collected from healthy pregnant women (n = 6). Second trimester placental explants (16–20 weeks, n = 5/group) were treated with lipopolysaccharide (LPS, to mimic bacterial infection) and ACE2, CCL2, IL-6/8 and TNFα mRNA was assessed. ChA-placentae exhibited increased ACE2 and CCL2 mRNA expression (p < 0.05). LPS increased cytokine and ACE2 mRNA in placental explants. Placental ACE2 protein localized to syncytiotrophoblast, fetal endothelium, extravillous trophoblast and in immune cells-subsets (M1/M2 macrophage and neutrophils) within the villous stroma. Significantly increased numbers of M1 macrophage and neutrophils were present in the ChA-placenta (p < 0.001). Subsets of peripheral immune cells from pregnant women express the ACE2 mRNA and protein. A greater fraction of granulocytes was positive for ACE2 protein expression compared to lymphocytes or monocytes. These data suggest that in pregnancies complicated by ChA, ACE2 positive immune cells in the maternal circulation have the potential to traffic SARS-CoV-2 virus to the placenta and increase the risk of vertical transmission to the placenta/fetus.
Graphene Bioelectronic Nose for the Detection of Odorants with Human Olfactory Receptor 2AG1
Authors: Goodwin Danielle M. , Walters Ffion , Ali Muhammad Munem , Daghigh Ahmadi Ehsaneh , Guy Owen J.
Published: July 2021

A real-time sensor for the detection of amyl butyrate (AB) utilising human olfactory receptor 2AG1 (OR2AG1), a G-protein coupled receptor (GPCR) consisting of seven transmembrane domains, immobilized onto a graphene resistor is demonstrated. Using CVD graphene as the sensor platform, allows greater potential for more sensitive detection than similar sensors based on carbon nanotubes, gold or graphene oxide platforms. A specific graphene resistor sensor was fabricated and modified via non-covalent π–π stacking of 1,5 diaminonaphthalene (DAN) onto the graphene channel, and subsequent anchoring of the OR2AG1 receptor to the DAN molecule using glutaraldehyde coupling. Binding between the target odorant, amyl butyrate, and the OR2AG1 receptor protein generated a change in resistance of the graphene resistor sensor. The functionalized graphene resistor sensors exhibited a linear sensor response between 0.1–500 pM and high selectively towards amyl butyrate, with a sensitivity as low as 500 fM, whilst control measurements using non-specific esters, produced a negligible sensor response. The approach described here provides an alternative sensing platform that can be used in bioelectronic nose applications.
Effect of Poly(Titanium Oxide) on the Viscoelastic and Thermophysical Properties of Interpenetrating Polymer Networks
Authors: Tsebriienko Tamara , Popov Anatoli I.
Published: July 2021

The influence of poly(titanium oxide) obtained using the sol-gel method in 2-hydroxyethyl methacrylate medium on the viscoelastic and thermophysical properties of interpenetrating polymer networks (IPNs) based on cross-linked polyurethane (PU) and poly(hydroxyethyl methacrylate) (PHEMA) was studied. It was found that both the initial (IPNs) and organo-inorganic interpenetrating polymer networks (OI IPNs) have a two-phase structure by using methods of dynamic mechanical analysis (DMA) and differential scanning calorimetry (DSC). The differential scanning calorimetry methods and scanning electron microscopy (SEM) showed that the presence of poly(titanium oxide) increases the compatibility of the components of IPNs. It was found that an increase in poly(titanium oxide) content leads to a decrease in the intensity of the relaxation maximum for PHEMA phase and an increase in the effective crosslinking density due to the partial grafting of the inorganic component to acrylate. It was shown that the topology of poly(titanium oxide) structure has a significant effect on the relaxation behavior of OI IPNs samples. According to SEM, a uniform distribution of the inorganic component in the polymer matrix is observed without significant aggregation.
The Isocyanide Complexes cis-[MCl2(CNC6H4-4-X)2] (M = Pd, Pt; X = Cl, Br) as Tectons in Crystal Engineering Involving Halogen Bonds
Authors: Kashina Maria V. , Ivanov Daniil M. , Kinzhalov Mikhail A.
Published: July 2021

The isocyanide complexes cis-[MCl2(CNC6H4-4-X)2] (M = Pd; X = Cl, Br; M = Pt; X = Br) form isomorphous crystal structures exhibiting the Cl/Br and Pd/Pt exchanges featuring 1D chains upon crystallisation. Crystal packing is supported by the C–X···X–C halogen bonds (HaBs), C–H···X–C hydrogen bonds (HB), X···M semicoordination, and C···C contacts between the C atoms of aryl isocyanide ligands. The results of DFT calculations and topological analysis indicate that all the above contact types belong to attractive noncovalent interactions. A projection of the electron localization function (ELF) and an inspection of the electron density (ED) and the electrostatic potential (ESP) reveal the amphiphilic nature of X atoms playing the role of HaB donors, HaB and HB acceptors, and a nucleophilic partner in X···M semicoordination.
An Online Risk Tool for Predicting Type 2 Diabetes Mellitus
Authors: Alix Gian , Huang Huaxiong , Guergachi Aziz , Keshavjee Karim , Gao Xin
Published: July 2021

An online risk prediction tool is developed to calculate a user’s risk of developing type II diabetes mellitus (T2DM). The risk prediction is based on the user’s input of medical lab information, such as age, sex, body mass index, fasting blood sugar, triglycerides, and high-density lipoprotein levels. The calculator is modelled using a logistic regression model, and it is trained using the medical records of over ten thousand Canadian patients. This newly developed tool is intended to serve physicians and patients in predicting future diabetes risk and take early preventive measures.
Sudden Cardiac Death Caused by a Fatal Association of Hypertrophic Cardiomyopathy (MYH7, p.Arg719Trp), Heterozygous Familial Hypercholesterolemia (LDLR, p.Gly343Lys) and SARS-CoV-2 B.1.1.7 Infection
Authors: Marziliano Nicola , Medoro Alessandro , Mignogna Donatella , Saccon Giovanni , Folzani Stefano , Reverberi Claudio , Russo Claudio , Intrieri Mariano
Published: July 2021

Hypertrophic cardiomyopathy (HCM) and heterozygous familial hypercholesterolemia (HeFH), two of the most common genetic cardiovascular disorders, can lead to sudden cardiac death. These conditions could be complicated by concomitant severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection as in the case herein described. A young amateur soccer player died in late October 2020 after a fatal arrhythmia and the autopsy revealed the presence of HCM with diffuse non-obstructive coronary disease. The molecular autopsy revealed a compound condition with a first mutation in the MYH7 gene (p.Arg719Trp) and a second mutation in the LDLR gene (p.Gly343Cys): both have already been described as associated with HCM and HeFH, respectively. In addition, molecular analyses showed the presence of SARS-CoV-2 lineage B.1.1.7 (UK variant with high titer in the myocardium. Co-segregation analysis within the family (n = 19) showed that heterozygous LDLR mutation was maternally inherited, while the heterozygous MYH7 genetic lesion was de novo. All family member carriers of the LDLR mutation (n = 13) had systematic higher LDL plasma concentrations and positive records of cardiac and vascular ischemic events at young age. Considering that HCM mutations are in themselves involved in the predisposition to malignant arrhythmogenicity and HeFH could cause higher risk of cardiac complications in SARS-CoV-2 infection, this case could represent an example of a potential SARS-CoV-2 infection role in triggering or unmasking inherited cardiovascular disease, whose combination might represent the cause of fatal arrhythmia at such a young age. Additionally, it can provide clues in dating the presence of the SARS-CoV-2 lineage B.1.1.7 in Northern Italy in the early phases of the second pandemic wave.
Intra- and Inter-Rater Reliability of Strength Measurements Using a Pull Hand-Held Dynamometer Fixed to the Examiner’s Body and Comparison with Push Dynamometry
Authors: González-Rosalén Javier , Benítez-Martínez Josep Carles , Medina-Mirapeix Francesc , Cuerda-Del Pino Alba , Cervelló Antonio , Martín-San Agustín Rodrigo
Published: July 2021

Hand held dynamometers (HHDs) are the most used method to measure strength in clinical sitting. There are two methods to realize the assessment: pull and push. The purpose of the present study was to evaluate the intra- and inter-rater reliability of a new measurement modality for pull HHD and to compare the inter-rater reliability and agreement of the measurements. Forty healthy subjects were evaluated by two assessors with different body composition and manual strength. Fifteen isometric tests were performed in two sessions with a one-week interval between them. Reliability was examined using the intra-class correlation (ICC) and the standard error of measurement (SEM). Agreement between raters was examined using paired t-tests. Intra- and inter-rater reliability for the tests performed with the pull HHD showed excellent values, with ICCs ranging from 0.991 to 0.998. For tests with values higher than 200 N, push HHD showed greater differences between raters than pull HHD. Pull HHD attached to the examiner’s body is a method with excellent reliability to measure isometric strength and showed better agreement between examiners, especially for those tests that showed high levels of strength. Pull HHD is a new alternative to perform isometric tests with less rater dependence.
The Psychological Impact of Coronavirus Pandemic Restrictions in Italy. The Mediating Role of the Fear of COVID-19 in the Relationship between Positive and Negative Affect with Positive and Negative Outcomes
Authors: Zammitti Andrea , Imbrogliera Chiara , Russo Angela , Zarbo Rita , Magnano Paola
Published: July 2021

Italy was quickly hit hard by the coronavirus. ‘Lockdown’ has significantly impacted the psychological health, personal wellbeing and quality of life of the people. The study aims to explore the relationship between positive and negative affect, as well as positive (spiritual well-being and flourishing) and negative outcomes (psychological distress caused by a traumatic life event in terms of perception of PTSD symptoms) on Italian adults during the lockdown period. Data was collected between April and May 2020. The participants were 281 Italian adults aged between 18 and 73 years. The survey was composed of the following measures: Flourishing Scale, Jarel Spiritual Well-Being scale, Positive and Negative Affect Schedule, Impact of Event Scale—Revised, Fear of COVID-19. The mediational analysis shows that fear of COVID-19 fully mediates the relationship between negative affect and spiritual well-being and flourishing; fear of COVID-19 partially mediates the relationship between negative affect and PTSD symptoms; the positive affect shows only direct effects on positive outcomes. Therefore, fear of COVID-19 does not play any mediation role. Implications for psychological interventions and future research will be discussed.
Comparison of DSOGI-Based PLL for Phase Estimation in Three-Phase Weak Grids
Authors: Pinto Jorge , Carvalho Adriano , Rocha Agostinho , Araújo Armando
Published: July 2021

The paper presents a summary of different double second-order generalized integrator (DSOGI)-based phase-locked loop (PLL) algorithms for synchronization with three-phase weak grids. The different methods are compared through simulation under a variety of grid conditions, such as unbalanced phase voltages, high low-order harmonics distortion, frequency steps, phase jumps, and voltage sags. Following the simulation results, the three methods that have shown the overall best results are compared through an experimental setup for further results validation under operation with a voltage-source converter. Based on the obtained results, a benchmark table is presented that allows ranking the performance of the tested methods for different expected grid conditions.