bluuebunny/crossref_metadata_2025 huggingface dataset:
An Elliptical-Shaped Dual-Band UWB Notch Antenna for Wireless Applications
Authors: Kumar Om Prakash , Ali Tanweer , Kumar Pramod , Kumar Pradeep , Anguera Jaume
Published: January 2023

This paper discusses an elliptical ultrawideband (UWB) antenna and a dual-band UWB notch antenna. To achieve a UWB bandwidth, two corner cuts are etched into the rectangular slot on the partial ground plane. An inverted-U-shaped and conductor-shaped resonator are utilized to achieve dual-band notch characteristics on a partial ground plane. The suggested antenna has an overall dimension of 24×32 mm2. The suggested UWB antenna has a gain of 4.9 dB, a bandwidth of 2.5–11 GHz, a linear phase response, a group delay of less than 1 ns, and a steady radiation pattern. The suggested UWB notch rejects WLAN and ITU bands from 5.2–5.7 GHz and 7.2–8.5 GHz, respectively, with an impedance bandwidth of 2.5–11 GHz. The UWB notch antenna features a linear phase, a group delay of less than 1 ns, and a stable radiation pattern.
A Collaborative Monitoring Method for Traffic Situations under Urban Road Emergencies
Authors: Xiang Min , An Yulin
Published: January 2023

The complex and diverse urban road traffic environments make it difficult to accurately assess road traffic situations. This paper proposes a collaborative monitoring method for urban road traffic situational assessment during emergency events. This method is applied to a monitoring network mapped by road geographic relations. When an emergency event is captured by a monitoring node in the network, road traffic situational awareness is completed by an activation function. Then, the Incidence matrix of the emergency event is constructed based on the node degree of this monitoring node. The collaborative node set and collaborative monitoring area are formed dynamically from this Incidence matrix. Finally, the AHP and EM combination weight calculation method based on Game Theory (GT-AHP-EM) is used to fuse the data of various information in the collaborative monitoring area to predict the current road traffic trend. The experiments show that the collaborative monitoring method can effectively assess road traffic conditions and enhance the accuracy of road traffic trend prediction.
Descriptive Parameters and Its Hysteresis of the Group Separation and Recombination in Bicycle Points Races: Leader’s Velocity and Speed Difference between Leader and Main Group
Authors: Okumura Fumihiro , Yokoyama Keiko , Yamamoto Yuji
Published: January 2023

This study examined the descriptive parameters for separation and recombination processes in a cycling points race. The candidate descriptive parameters were the speed of the leading cyclist and the main group and the difference between their time and speed. We focused on the transition between the four states of peloton configuration (dense state, stretched state, divided state, and escape and dense state) defined by previous studies that occur during the points race. As a result, it was found that the distribution of the leader’s velocity and the speed difference significantly differed when the groups were separated and recombined compared to when the state did not change. It was also examined whether the separation and recombination processes had a phenomenon such as a hysteresis depending on the present state. Regarding the leader velocity and the speed difference between the leader and the main group, the state of the group was not uniquely determined by the speed difference, and the influence of the speed difference for separation or recombination depended on the state; that is, there was asymmetry in separation and recombination in a points race. These suggest that the cyclists need the ability to choose an appropriate speed and distance from other cyclists depending on the situation.
Dynamical Effects of the Increase of the Axle Load on European Freight Railway Vehicles
Authors: Bosso Nicola , Magelli Matteo , Zampieri Nicolò
Published: January 2023

The development of an efficient freight railway system requires minimizing the travel time and maximizing the load capacity of trains. This objective can be achieved through three different strategies which can be adopted separately or in synergy. These strategies substantially consist of improvement of the load capacity of a single vehicle, increase in the train length, and increment of the vehicle velocity. The option to adopt simultaneously all three strategies is possible only when operating on dedicated infrastructures and specifically designing the vehicles and the track. This work shows the effect of the increment of the axle load, over the actual Italian limitation, on the most important indicators defined by the UIC regulation to homologate the vehicles. The calculations have been performed on a high-quality real track using a numerical model of a vehicle based on the Y25 bogie. In order to take into account higher axle loads, the vehicle primary suspension has been redesigned. The results show that an increment of the axle load is feasible until an axle load of 32.5 ton if speed is limited to 80 km/h, or until 30 ton if speed is limited to 120 km/h.
An Experimental Setup to Detect the Crack Fault of Asymmetric Rotors Based on a Deep Learning Method
Authors: Wang Chongyu , Zheng Zhaoli , Guo Ding , Liu Tianyuan , Xie Yonghui , Zhang Di
Published: January 2023

Crack is a common fault of rotor systems. The research on crack fault detection methods is mainly divided into numerical and experimental studies. In numerical research, the current fault detection algorithms based on deep learning are mostly applied to bearings and gearboxes, and there are few studies on rotor fault diagnosis. In experimental research, the rotors used in an experiment are mostly single-span rotors. However, there are complex structures such as multi-span rotor systems in the actual industrial field. Thus, the fault detection algorithms that have been successfully applied on single-span rotors have not been verified on complex rotor systems. To obtain a fault signal close to the actual asymmetric shaft system of an asymmetric rotor system and validate the fault detection method, the crack fault detection platform is designed and built independently. We measure the vibration signals of three channels under five working conditions and establish an intelligent detection method for crack location based on a residual network. The factors that influence fault detection performance are analyzed, and the influence laws are discussed. Results show that the accuracy and anti-noise performance of the proposed method are higher than those of the commonly used machine learning. The average accuracy is 100% when SNR (signal-to-noise ratio) is greater than or equal to −2 dB, and the average accuracy is 98.2% when SNR is −4 dB.
Novel Pr-Doped BaLaInO4 Ceramic Material with Layered Structure for Proton-Conducting Electrochemical Devices
Authors: Tarasova Nataliia , Bedarkova Anzhelika , Animitsa Irina
Published: January 2023

One of the urgent tasks of applied materials science is the creation of novel high-effective materials with target properties. In the area of energy systems, there is a problem in the conversion of chemical energy to electricity without mechanical work. Hydrogen energy provides a way using electrochemical devices such as protonic ceramic fuel cells. Novel advanced proton-conducting materials with the top characteristics of target properties are strictly needed. Layered perovskites are a novel and promising class of protonic conductors. In this work, the layered perovskite BaLa0.9Pr0.1InO4 was obtained and investigated as a protonic conductor for the first time. The possibility for water intercalation and proton transport is proved. It was shown that isovalent doping Pr3+ → La3+ leads to an increase in the crystal lattice size, proton concentration and proton mobility. The proton conductivity value for doped BaLa0.9Pr0.1InO4 composition is 18 times greater than for undoped BaLaInO4 composition. Layered perovskites based on BaLaInO4 are promising materials for application in proton-conducting electrochemical devices.
Calculation of Theoretical Travel Time and Automatic Picking of Actual Travel Time in Seismic Data
Authors: Gao Wenqi , Wang Youxue , Yang Yang , Peng Sanxi , Yu Songping , Liu Lu , Yan Lei
Published: January 2023

We used the ray tracing technique based on the IASP91 Earth model to calculate the travel times in order to identify the phases. This technique can calculate the travel times for the seismic phases in the conventional travel time tables. The waveform data received from the stations in the Guangxi area are selected for analysis and discussion. The outcomes of the numerical modeling and its use demonstrate that there is good agreement in terms of the absolute differences between the calculated and theoretical travel times from the ISAP91 tables. The relative residuals are determined directly from the actual arrival times picking during the correlation analysis, and the validity of the travel time method for picking seismic phases by correlation analysis can be demonstrated.
Circular Bioeconomy and the Forest-Wood Sector: Bridging the Gap between Policies and Disadvantaged Forest Areas
Authors: Borrello Massimiliano , Altomonte Elisa , Cembalo Luigi , D’Amico Valentina , Lombardi Alessia
Published: January 2023

The adoption of circular bioeconomy (CBE) strategies in forest-wood supply chains is a possible avenue for the future of this sector. However, the uptake of CBE models may face several barriers in the coming years, particularly in disadvantaged forest areas lacking appropriate resources and a suitable business environment to start radical innovation pathways. Based on interviews with 29 representatives (business actors and other key informants) of the forest-food sector of the Salerno province (Italy), the current study investigated the main strengths, weaknesses, opportunities, and threats (SWOT) involved in the transition of disadvantaged forest areas into a circular bioeconomy. Respondents also contributed to identifying the most suitable strategies in order to foster the CBE transition in the territory at hand. The paper offers an outlook for the potentialities of CBE in disadvantaged forest areas for policy actors, willing to bridge the gap between CBE agendas and territorial development challenges. The role of policy actors is particularly crucial, in order to patronize investments, stimulate improved know-how and cooperation, and fix policy inconsistencies related to biomass valorization.
Spatial Identification, Prevention and Control of Epidemics in High-Rise Residential Areas Based on Wind Environments
Authors: Zhang Jianxin , Jiang Shenqiang , Zhao Jingyuan , Ma Xuan
Published: January 2023

The wind environment in residential areas can exert a direct or indirect influence on the spread of epidemics, with some scholars paying particular attention to the epidemic prevention and control of residential areas from the perspective of wind environments. As a result, it is urgent to re-examine the epidemic prevention response of residential spaces. Taking high-rise residential areas in Xi’an as an example, the article defines the air flow field area based on on-site wind environment measurements, crowd behavior annotation, and CFD simulation. Using the double-effect superposition of crowd behavior and risk space, the paper undertook a multiple identification strategy of epidemic prevention space. The identification methods and management and control strategies of epidemic prevention in high-rise residential areas are proposed. Additionally, the living environment of residential areas is optimized, and a healthy residential space is created. The transformation from concept and calls for action to space implementation is made to provide a reference for improving the space management and control capabilities in high-rise residential areas in China. The results of this study can be used as a guideline for future residential planning and design from the perspective of preventing airborne diseases.
Mathematical Model Investigation of a Technological Structure for Personal Data Protection
Authors: Romansky Radi
Published: January 2023

The contemporary digital age is characterized by the massive use of different information technologies and services in the cloud. This raises the following question: “Are personal data processed correctly in global environments?” It is known that there are many requirements that the Data Controller must perform. For this reason, this article presents a point of view for transferring some activities for personal data processing from a traditional system to a cloud environment. The main goal is to investigate the differences between the two versions of data processing. To achieve this goal, a preliminary deterministic formalization of the two cases using a Data Flow Diagram is made. The second phase is the organization of a mathematical (stochastic) model investigation on the basis of a Markov chain apparatus. Analytical models are designed, and their solutions are determined. The final probabilities for important states are determined based on an analytical calculation, and the higher values for the traditional version are defined for data processing in registers (“2”: access for write/read −0.353; “3”: personal data updating −0.212). The investigation of the situations based on cloud computing determines the increasing probability to be “2”. Discussion of the obtained assessment based on a graphical presentation of the analytical results is presented, which permits us to show the differences between the final probabilities for the states in the two versions of personal data processing.
A Combination of Fuzzy Techniques and Chow Test to Detect Structural Breaks in Time Series
Authors: Novák Vilém , Truong Thi Thanh Phuong
Published: January 2023

In a series of papers, we suggested a non-statistical method for the detection of structural breaks in a time series. It is based on the applications of special fuzzy modeling methods, namely Fuzzy transform (F-transform) and selected methods of Fuzzy Natural Logic (FNL). In this paper, we combine our method with the principles of the classical Chow test, which is a well-known statistical method for testing the presence of a structural break. The idea is to construct testing statistics similar to that of the Chow test which is formed from components of the first-degree F-transform. These components contain an estimation of the average values of the tangents (slopes) of the time series over an imprecisely specified time interval. In this paper, we illustrate our method and its statistical test on a real-time series and compare it with three classical statistical methods.
Acknowledgment to the Reviewers of BDCC in 2022
Authors:   BDCC Editorial Office
Published: January 2023

High-quality academic publishing is built on rigorous peer review [...]
Primary Hepatocyte Isolation and Cultures: Technical Aspects, Challenges and Advancements
Authors: Kaur Impreet , Vasudevan Ashwini , Rawal Preety , Tripathi Dinesh M. , Ramakrishna Seeram , Kaur Savneet , Sarin Shiv K.
Published: January 2023

Hepatocytes are differentiated cells that account for 80% of the hepatic volume and perform all major functions of the liver. In vivo, after an acute insult, adult hepatocytes retain their ability to proliferate and participate in liver regeneration. However, in vitro, prolonged culture and proliferation of viable and functional primary hepatocytes have remained the major and the most challenging goal of hepatocyte-based cell therapies and liver tissue engineering. The first functional cultures of rat primary hepatocytes between two layers of collagen gel, also termed as the “sandwich cultures”, were reported in 1989. Since this study, several technical developments including choice of hydrogels, type of microenvironment, growth factors and culture conditions, mono or co-cultures of hepatocytes along with other supporting cell types have evolved for both rat and human primary hepatocytes in recent years. All these improvements have led to a substantial improvement in the number, life-span and hepatic functions of these cells in vitro for several downstream applications. In the current review, we highlight the details, limitations and prospects of different technical strategies being used in primary hepatocyte cultures. We discuss the use of newer biomaterials as scaffolds for efficient culture of primary hepatocytes. We also describe the derivation of mature hepatocytes from other cellular sources such as induced pluripotent stem cells, bone marrow stem cells and 3D liver organoids. Finally, we also explain the use of perfusion-based bioreactor systems and bioengineering strategies to support the long-term function of hepatocytes in 3D conditions.
In-Silico and In-Vitro Analysis of the Novel Hybrid Comprehensive Stage II Operation for Single Ventricle Circulation
Authors: Das Arka , Hameed Marwan , Prather Ray , Farias Michael , Divo Eduardo , Kassab Alain , Nykanen David , DeCampli William
Published: January 2023

Single ventricle (SV) anomalies account for one-fourth of all congenital heart disease cases. The existing palliative treatment for this anomaly achieves a survival rate of only 50%. To reduce the trauma associated with surgical management, the hybrid comprehensive stage II (HCSII) operation was designed as an alternative for a select subset of SV patients with the adequate antegrade aortic flow. This study aims to provide better insight into the hemodynamics of HCSII patients utilizing a multiscale Computational Fluid Dynamics (CFD) model and a mock flow loop (MFL). Both 3D-0D loosely coupled CFD and MFL models have been tuned to match baseline hemodynamic parameters obtained from patient-specific catheterization data. The hemodynamic findings from clinical data closely match the in-vitro and in-silico measurements and show a strong correlation (r = 0.9). The geometrical modification applied to the models had little effect on the oxygen delivery. Similarly, the particle residence time study reveals that particles injected in the main pulmonary artery (MPA) have successfully ejected within one cardiac cycle, and no pathological flows were observed.
Extracellular Vesicles as Regulators of the Extracellular Matrix
Authors: Patel Neil J. , Ashraf Anisa , Chung Eun Ji
Published: January 2023

Extracellular vesicles (EVs) are small membrane-bound vesicles secreted into the extracellular space by all cell types. EVs transfer their cargo which includes nucleic acids, proteins, and lipids to facilitate cell-to-cell communication. As EVs are released and move from parent to recipient cell, EVs interact with the extracellular matrix (ECM) which acts as a physical scaffold for the organization and function of cells. Recent work has shown that EVs can modulate and act as regulators of the ECM. This review will first discuss EV biogenesis and the mechanism by which EVs are transported through the ECM. Additionally, we discuss how EVs contribute as structural components of the matrix and as components that aid in the degradation of the ECM. Lastly, the role of EVs in influencing recipient cells to remodel the ECM in both pathological and therapeutic contexts is examined.
Non-Ionic Osmotic Stress Induces the Biosynthesis of Nodulation Factors and Affects Other Symbiotic Traits in Sinorhizobium fredii HH103
Authors: Fuentes-Romero Francisco , Moyano-Bravo Isamar , Ayala-García Paula , Rodríguez-Carvajal Miguel Ángel , Pérez-Montaño Francisco , Acosta-Jurado Sebastián , Ollero Francisco Javier , Vinardell José-María
Published: January 2023

(1) Background: Some rhizobia, such as Rhizobium tropici CIAT 899, activate nodulation genes when grown under osmotic stress. This work aims to determine whether this phenomenon also takes place in Sinorhizobium fredii HH103. (2) Methods: HH103 was grown with and without 400 mM mannitol. β-galactosidase assays, nodulation factor extraction, purification and identification by mass spectrometry, transcriptomics by RNA sequencing, motility assays, analysis of acyl-homoserine lactones, and indole acetic acid quantification were performed. (3) Results: Non-ionic osmotic stress induced the production of nodulation factors. Forty-two different factors were detected, compared to 14 found in the absence of mannitol. Transcriptomics indicated that hundreds of genes were either activated or repressed upon non-ionic osmotic stress. The presence of 400 mM mannitol induced the production of indole acetic acid and acyl homoserine lactones, abolished swimming, and promoted surface motility. (4) Conclusions: In this work, we show that non-ionic stress in S. fredii HH103, caused by growth in the presence of 400 mM mannitol, provokes notable changes not only in gene expression but also in various bacterial traits, including the production of nodulation factors and other symbiotic signals.
Targeting Apoptotic Pathway of Cancer Cells with Phytochemicals and Plant-Based Nanomaterials
Authors: Wani Atif Khurshid , Akhtar Nahid , Mir Tahir ul Gani , Singh Rattandeep , Jha Prakash Kumar , Mallik Shyam Kumar , Sinha Shruti , Tripathi Surya Kant , Jain Abha , Jha Aprajita , Devkota Hari Prasad , Prakash Ajit
Published: January 2023

Apoptosis is the elimination of functionally non-essential, neoplastic, and infected cells via the mitochondrial pathway or death receptor pathway. The process of apoptosis is highly regulated through membrane channels and apoptogenic proteins. Apoptosis maintains cellular balance within the human body through cell cycle progression. Loss of apoptosis control prolongs cancer cell survival and allows the accumulation of mutations that can promote angiogenesis, promote cell proliferation, disrupt differentiation, and increase invasiveness during tumor progression. The apoptotic pathway has been extensively studied as a potential drug target in cancer treatment. However, the off-target activities of drugs and negative implications have been a matter of concern over the years. Phytochemicals (PCs) have been studied for their efficacy in various cancer cell lines individually and synergistically. The development of nanoparticles (NPs) through green synthesis has added a new dimension to the advancement of plant-based nanomaterials for effective cancer treatment. This review provides a detailed insight into the fundamental molecular pathways of programmed cell death and highlights the role of PCs along with the existing drugs and plant-based NPs in treating cancer by targeting its programmed cell death (PCD) network.
The Immunogenicity of a VLP-based Malaria Vaccine Targeting CSP in Pregnant and Neonatal Mice
Authors: Jelínková Lucie , Roberts Bryce , Ajayi Diane T. , Peabody David S. , Chackerian Bryce
Published: January 2023

Maternal antibodies are passively transferred to the fetus via the placenta during gestation and can play an important role in protecting the newborn from infection. For example, in malaria-endemic regions, maternal antibodies likely provide substantial protection against Plasmodium falciparum malaria in the first 6 months of life. However, circulating maternal antibodies can also interfere with vaccine efficacy. Here, we used a mouse maternal transfer model to evaluate whether maternal antibodies interfere with the responsiveness to a virus-like particle (VLP)-based vaccine targeting the CIS43 epitope of the malaria circumsporozoite protein (CSP). We found immunized dams passively transfer to pups high levels of anti-CSP IgG antibodies that steadily decline as the animals age. We also found that the neonatal offspring of immunized mice do not respond to de novo immunization with the CIS43-targeted VLP vaccine until maternal antibody titers decline below an inhibitory threshold. These findings may have important implications for delineating the delicate balance between protection conferred by maternal antibodies and the offspring’s ability to respond to immunization.
Updated Virophage Taxonomy and Distinction from Polinton-like Viruses
Authors: Roux Simon , Fischer Matthias G. , Hackl Thomas , Katz Laura A. , Schulz Frederik , Yutin Natalya
Published: January 2023

Virophages are small dsDNA viruses that hijack the machinery of giant viruses during the co-infection of a protist (i.e., microeukaryotic) host and represent an exceptional case of “hyperparasitism” in the viral world. While only a handful of virophages have been isolated, a vast diversity of virophage-like sequences have been uncovered from diverse metagenomes. Their wide ecological distribution, idiosyncratic infection and replication strategy, ability to integrate into protist and giant virus genomes and potential role in antiviral defense have made virophages a topic of broad interest. However, one limitation for further studies is the lack of clarity regarding the nomenclature and taxonomy of this group of viruses. Specifically, virophages have been linked in the literature to other “virophage-like” mobile genetic elements and viruses, including polinton-like viruses (PLVs), but there are no formal demarcation criteria and proper nomenclature for either group, i.e., virophage or PLVs. Here, as part of the ICTV Virophage Study Group, we leverage a large set of genomes gathered from published datasets as well as newly generated protist genomes to propose delineation criteria and classification methods at multiple taxonomic ranks for virophages ‘sensu stricto’, i.e., genomes related to the prototype isolates Sputnik and mavirus. Based on a combination of comparative genomics and phylogenetic analyses, we show that this group of virophages forms a cohesive taxon that we propose to establish at the class level and suggest a subdivision into four orders and seven families with distinctive ecogenomic features. Finally, to illustrate how the proposed delineation criteria and classification method would be used, we apply these to two recently published datasets, which we show include both virophages and other virophage-related elements. Overall, we see this proposed classification as a necessary first step to provide a robust taxonomic framework in this area of the virosphere, which will need to be expanded in the future to cover other virophage-related viruses such as PLVs.
Characterization of Microarchitectures, Stiffness and Strength of Human Trabecular Bone Using Micro-Computed Tomography (Micro-CT) Scans
Authors: El-Gizawy Ahmed Sherif , Ma Xuewei , Pfeiffer Ferris , Schiffbauer James D. , Selly Tara
Published: January 2023

The present work presents evaluation and experimental verification of the use of X-ray computed tomographic microscopy (micro-CT) for accurate characterization of geometry, microarchitecture, and stiffness properties of bones. These properties are crucial for designing and building optimized implants for joint and dental reconstruction applications. High-resolution micro-CT scans would provide more detailed and accurate information about the microarchitecture and density distribution across patient bones. Nevertheless, micro-CT applications on live patients require invasive procedures involving small bone biopsy specimens. Alternatively, micro-CT could be used on samples collected from selected cadavers of different age, gender, and race groups to establish a database that could be used for providing useful microarchitecture information. The micro-CT scans of investigated bone samples reveal that the trabecular bone is anisotropic and heterogeneous. The results also showed considerable degree of parametric variability and uncertainty on microarchitecture and stiffness properties of patient’s trabecular bone.
The Relationship between the Expression of GATA4 and GATA6 with the Clinical Characteristics and Prognosis of Resectable Pancreatic Adenocarcinoma
Authors: Heredia-Soto Victoria , Gutiérrez-Sainz Laura , Ghanem Ismael , Guerra Laura , Palacios Elena , de Uribe Marta , Trilla-Fuertes Lucía , de Miguel María , Cejas Paloma , Medina Laura , Calderón José Miguel , Viñal David , Mendiola Marta , Feliu Jaime
Published: January 2023

GATA4 and GATA6 are transcription factors involved in the differentiation and development of PDAC. GATA6 expression is related to the classic molecular subtype, while its absence is related to the basal-like molecular subtype. The aim was to determine the clinical utility of IHC determination of GATA4 and GATA6 in a series of patients with resected PDAC. GATA4 and GATA6 expression was studied by IHC in TMA samples of normal tissue, PanIN, tumor tissue and lymph node metastases from a series of 89 patients with resected PDAC. Its relationship with clinicopathologic variables and the outcome was investigated. Seventy-two (81%) tumors were GATA6+ and 37 (42%) were GATA4+. While GATA4 expression was reduced during tumor progression, GATA6 expression remained highly conserved, except in lymph node metastases. All patients with early stages and well-differentiated tumors were GATA6+. The absence of GATA4 expression was related to smoking. Patients with GATA4+ or GATA6+ tumors had significantly lower Ca 19.9 levels. The expression of GATA4 and GATA6 was related to DFS, being more favorable in the GATA4+/GATA6+ group. The determination of the expression of GATA4 and GATA6 by IHC is feasible and provides complementary clinical and prognostic information that can help improve the stratification of patients with PDAC.
Administration of Epidermal Growth Factor (EGF) and Basic Fibroblast Growth Factor (bFGF) to Induce Neural Differentiation of Dental Pulp Stem Cells (DPSC) Isolates
Authors: Lott Keegan , Collier Paris , Ringor Marc , Howard Katherine M. , Kingsley Karl
Published: January 2023

The aging populations in many countries have developed many chronic illnesses and diseases, including chronic neurologic conditions such as Parkinson’s and Azheimer’s diseases. Many new lines of research and treatment are focusing on the potential for neurologic regeneration using mesenchymal stem cells (MSCs) in the rapidly growing field of regenerative medicine. This may include dental pulp stem cells (DPSCs), which have recently been demonstrated to produce neuronal precursors. Based upon this evidence, the primary aim of this study was to determine if the growth factors used in MSC-based studies are sufficient to induce neuronal differentiation among DPSCs. Using an existing biorepository, n = 16 DPSC isolates were thawed and cultured for this study, which revealed several subpopulations of rapid-, intermediate-, and slowly dividing DPSCs. Administration of epidermal growth factor (EGF) and basic fibroblast growth factor (bFGF) were sufficient to induce differential changes in growth and viability mainly among some of the rapidly growing DPSCs (n = 4). These phenotypic changes included expression of neural differentiation markers including Sox1, Pax6 and NF-M, which were observed only among those DPSC isolates not expressing early odontoblast-specific biomarkers such as ALP and DSPP. Future studies will be needed to confirm if these methods are sufficient to induce consistent and reliable induction of DPSCs towards neuronal specific differentiation.
Gene Therapy with p14/tBID Induces Selective and Synergistic Apoptosis in Mutant Ras and Mutant p53 Cancer Cells In Vitro and In Vivo
Authors: Fine Robert L. , Mao Yuehua , Garcia-Carracedo Dario , Su Gloria H. , Qiu Wanglong , Hochfeld Uri , Nichols Gwen , Li Yong-Liang , Dinnen Richard D. , Raffo Anthony , Brandt-Rauf Paul W.
Published: January 2023

Any gene therapy for cancer will be predicated upon its selectivity against cancer cells and non-toxicity to normal cells. Therefore, safeguards are needed to prevent its activation in normal cells. We designed a minimal p14ARF promoter with upstream Ap1 and E2F enhancer elements and a downstream MDR1 inhibitory element, TATA box, and a transcription initiation site (hereafter p14ARFmin). The modified p14ARFmin promoter was linked to bicistronic P14 and truncated BID (tBID) genes, which led to synergistic apoptosis via the intrinsic and extrinsic pathways of apoptosis when expressed. The promoter was designed to be preferentially activated by mutant Ras and completely inhibited by wild-type p53 so that only cells with both mutant Ras and mutant p53 would activate the construct. In comparison to most p53 gene therapies, this construct has selective advantages: (1) p53-based gene therapies with a constitutive CMV promoter cannot differentiate between normal cells and cancer cells, and can be toxic to normal cells; (2) our construct does not induce p21WAF/CIPI in contrast to other p53-based gene therapies, which can induce cell cycle arrest leading to increased chemotherapy resistance; (3) the modified construct (p14ARFmin-p14-tBID) demonstrates bidirectional control of its promoter, which is completely repressed by wild-type p53 and activated only in cells with both RAS and P53 mutations; and (4) a novel combination of genes (p14 and tBID) can synergistically induce potent intrinsic and extrinsic apoptosis in cancer cells.
Intra-Arterial Urokinase for Acute Superior Mesenteric Artery Occlusion: A Retrospective 12-Year Report of 13 Cases
Authors: Lin Being-Chuan , Wu Cheng-Hsien , Wong Yon-Cheong , Hung Sheng-Che , Hsin Ming-Che
Published: January 2023

This retrospective study aimed to evaluate the outcomes of 13 patients with acute superior mesenteric artery (SMA) occlusion who underwent intra-arterial urokinase thrombolysis between 2008 and 2020. On angiography, seven presented with complete SMA occlusion versus six with incomplete occlusion. The median time from abdominal pain to attempting urokinase thrombolysis was 15.0 h (interquartile range, 6.0 h). After urokinase therapy, bowel perfusion was restored with bowel preservation in six patients; however, treatment failed in the other seven patients. The degree of SMA occlusion (complete vs. incomplete, p = 0.002), degree of recanalisation (p = 0.012), and length of stay (p = 0.032) differed significantly between groups. Of the seven patients with complete SMA occlusion, six underwent bowel resection, of whom three died, and the remaining patient died of shock due to delayed surgery. Among the six patients with incomplete SMA occlusion, no bowel resection was performed. In our experience, intra-arterial urokinase thrombolysis may serve as an adjunctive treatment modality, being a potential replacement for open thrombectomy that is able to preserve the bowel and obviate surgery in cases of incomplete SMA occlusion; however, its use is unsuitable in cases of complete SMA occlusion, for which surgery is warranted.
Editorial to the Special Issue “Pathogenesis and Novel Therapeutics in Asthma”
Authors: Bazan-Socha Stanisława , Jakieła Bogdan
Published: January 2023

In recent years, substantial progress has been made in our understanding of asthma pathomechanisms, especially phenotyping [...]
Biology, Pathobiology and Gene Therapy of CNG Channel-Related Retinopathies
Authors: Gerhardt Maximilian J. , Priglinger Siegfried G. , Biel Martin , Michalakis Stylianos
Published: January 2023

The visual process begins with the absorption of photons by photopigments of cone and rod photoreceptors in the retina. In this process, the signal is first amplified by a cyclic guanosine monophosphate (cGMP)-based signaling cascade and then converted into an electrical signal by cyclic nucleotide-gated (CNG) channels. CNG channels are purely ligand-gated channels whose activity can be controlled by cGMP, which induces a depolarizing Na+/Ca2+ current upon binding to the channel. Structurally, CNG channels belong to the superfamily of pore-loop cation channels and share structural similarities with hyperpolarization-activated cyclic nucleotide (HCN) and voltage-gated potassium (KCN) channels. Cone and rod photoreceptors express distinct CNG channels encoded by homologous genes. Mutations in the genes encoding the rod CNG channel (CNGA1 and CNGB1) result in retinitis-pigmentosa-type blindness. Mutations in the genes encoding the cone CNG channel (CNGA3 and CNGB3) lead to achromatopsia. Here, we review the molecular properties of CNG channels and describe their physiological and pathophysiological roles in the retina. Moreover, we summarize recent activities in the field of gene therapy aimed at developing the first gene therapies for CNG channelopathies.
Data-Driven Phenotyping of Alzheimer’s Disease under Epigenetic Conditions Using Partial Volume Correction of PET Studies and Manifold Learning
Authors: Campanioni Silvia , González-Nóvoa José A. , Busto Laura , Agís-Balboa Roberto Carlos , Veiga César
Published: January 2023

Alzheimer’s disease (AD) is the most common form of dementia. An increasing number of studies have confirmed epigenetic changes in AD. Consequently, a robust phenotyping mechanism must take into consideration the environmental effects on the patient in the generation of phenotypes. Positron Emission Tomography (PET) is employed for the quantification of pathological amyloid deposition in brain tissues. The objective is to develop a new methodology for the hyperparametric analysis of changes in cognitive scores and PET features to test for there being multiple AD phenotypes. We used a computational method to identify phenotypes in a retrospective cohort study (532 subjects), using PET and Magnetic Resonance Imaging (MRI) images and neuropsychological assessments, to develop a novel computational phenotyping method that uses Partial Volume Correction (PVC) and subsets of neuropsychological assessments in a non-biased fashion. Our pipeline is based on a Regional Spread Function (RSF) method for PVC and a t-distributed Stochastic Neighbor Embedding (t-SNE) manifold. The results presented demonstrate that (1) the approach to data-driven phenotyping is valid, (2) the different techniques involved in the pipelines produce different results, and (3) they permit us to identify the best phenotyping pipeline. The method identifies three phenotypes and permits us to analyze them under epigenetic conditions.
Reappraisal of the Lymphatic Drainage System of the Distal Rectum: Functional Lymphatic Flow into the Presacral Space and Its Clinical Implication in Rectal Cancer Treatment
Authors: Yoo Ri-Na , Cho Hyeon-Min , Kye Bong-Hyeon , Lee Yoon-Suk , Kim Yi-Suk
Published: January 2023

Understanding the source and route of pelvic metastasis is essential to developing an optimal strategy for controlling local and systemic diseases of rectal cancer. This study aims to delineate the distribution of lymphatic channels and flow from the distal rectum. In fresh-frozen cadaveric hemipelvis specimens, the ligamentous attachment of the distal rectum to the pelvic floor muscles and the presacral fascia were evaluated. Using indocyanine green (ICG) fluorescence imaging, we simultaneously evaluated the gross anatomy of the lymphatic communication of the distal rectum. We also investigated the lymphatic flow in the pelvic cavity intraoperatively in rectal cancer patients who underwent radical rectal resection with total mesorectal excision (TME). In fresh cadavers, multiple small perforating lymphovascular branches exist in the retrorectal space, posteriorly connecting the mesorectum to the presacral fascia. The lymphatic flow from the distal rectum drains directly into the presacral space through the branches. In patients who underwent TME for rectal cancer, intraoperative ICG fluorescence signals were seen in the pelvic sidewalls and the presacral space. This anatomical study demonstrated that the lymphatic flow from the distal rectum runs directly to the pelvic lateral sidewalls and the presacral space, suggesting a possible route of metastasis in distal rectal cancer.
Combination of Conventional Drugs with Biocompounds Derived from Cinnamic Acid: A Promising Option for Breast Cancer Therapy
Authors: Meirelles Lyvia Eloiza de Freitas , Souza Maria Vitória Felipe de , Carobeli Lucimara Rodrigues , Morelli Fabrício , Mari Natália Lourenço , Damke Edilson , Shinobu Mesquita Cristiane Suemi , Teixeira Jorge Juarez Vieira , Consolaro Marcia Edilaine Lopes , Silva Vânia Ramos Sela da
Published: January 2023

Despite the options available for breast cancer (BC) therapy, several adverse effects and resistance limit the success of the treatment. Furthermore, the use of a single drug is associated with a high failure rate. We investigated through a systematic review the in vitro effects of the combination between conventional drugs and bioactive compounds derived from cinnamic acid in BC treatment. The information was acquired from the following databases: PubMed, Web of Science, Embase, Scopus, Lilacs and Cochrane library. We focused on “Cinnamates”, “Drug Combinations” and “Breast neoplasms” for publications dating between January 2012 and December 2022, based on the PRISMA statement. The references of the articles were carefully reviewed. Finally, nine eligible studies were included. The majority of these studies were performed using MCF-7, MDA-MB-231, MDA-MB-468 and BT-20 cell lines and the combination between cisplatin, paclitaxel, doxorubicin, tamoxifen, dactolisib and veliparib, with caffeic acid phenethyl ester, eugenol, 3-caffeoylquinic acid, salvianolic acid A, ferulic acid, caffeic acid, rosmarinic acid and ursolic acid. The combination improved overall conventional drug effects, with increased cytotoxicity, antimigratory effect and reversing resistance. Combining conventional drugs with bioactive compounds derived from cinnamic acid could emerge as a privileged scaffold for establishing new treatment options for different BC types.
Identification of microRNA Signatures in Peripheral Blood of Young Women as Potential Biomarkers for Metal Allergy
Authors: Zhang Zhang , Hosoki Maki , Oshima Masamitsu , Tajima Toyoko , Miyagi Mayu , Raman Swarnalakshmi , Raju Resmi , Matsuka Yoshizo
Published: January 2023

MicroRNA (miRNA) is a short (19–24 nucleotide) endogenous non-protein RNA that exists in the body and controls the translation process from genes to proteins. It has become useful as a diagnostic tool and a potential treatment target in cancer research. To explore the function of miRNA in contact dermatitis, female participants with a positive metal allergy diagnosis (n = 3) were enrolled along with additional female participants with no medical history of metal allergy (n = 3). A patch test was performed on each participant. Peripheral blood was collected from all the participants before the patch test and at days 3 and 7 after starting the patch test. After total RNA was obtained from peripheral blood leukocytes and cDNA was generated, microarray analysis was performed to analyze the large-scale circulating miRNA profile. Real-time polymerase chain reaction (RT-PCR) was then used to clarify the overall target miRNA expression. Downregulation of hsa-let-7d-5p, hsa-miR-24-3p, hsa-miR-23b-3p, hsa-miR-26b-5p, and hsa-miR-150-5p was found on day 7. Certain miRNAs were confirmed using RT-PCR. These peripheral blood miRNAs could be diagnostic biomarkers for metal allergies.
Oral Brincidofovir Therapy for Monkeypox Outbreak: A Focused Review on the Therapeutic Potential, Clinical Studies, Patent Literature, and Prospects
Authors: Imran Mohd. , Alshammari Mohammed Kanan , Arora Mandeep Kumar , Dubey Amit Kumar , Das Sabya Sachi , Kamal Mehnaz , Alqahtani Abdulaziz Saad Abdulrahman , Sahloly Mohammed Ahmed Yahya , Alshammari Ahmed Hammad , Alhomam Hessah Mohammed , Mahzari Aeshah Mousa , Abida  , Rabaan Ali A. , Dzinamarira Tafadzwa
Published: January 2023

The monkeypox disease (MPX) outbreak of 2022 has been reported in more than one hundred countries and is becoming a global concern. Unfortunately, only a few treatments, such as tecovirimat (TCV), are available against MPX. Brincidofovir (BCV) is a United States Food and Drug Administration (USFDA)-approved antiviral against smallpox. This article reviews the potential of BCV for treating MPX and other Orthopoxvirus (OPXVs) diseases. The literature for this review was collected from PubMed, authentic websites (USFDA, Chimerix), and freely available patent databases (USPTO, Espacenet, and Patentscope). BCV (a lipophilic derivative of cidofovir) has been discovered and developed by Chimerix Incorporation, USA. Besides smallpox, BCV has also been tested clinically for various viral infections (adenovirus, cytomegalovirus, ebola virus, herpes simplex virus, and double-stranded DNA virus). Many health agencies and reports have recommended using BCV for MPX. However, no health agency has yet approved BCV for MPX. Accordingly, the off-label use of BCV is anticipated for MPX and various viral diseases. The patent literature revealed some important antiviral compositions of BCV. The authors believe there is a huge opportunity to create novel, inventive, and patentable BCV-based antiviral therapies (new combinations with existing antivirals) for OPXVs illnesses (MPX, smallpox, cowpox, camelpox, and vaccinia). It is also advised to conduct drug interaction (food, drug, and disease interaction) and drug resistance investigations on BCV while developing its combinations with other medications. The BCV-based drug repurposing options are also open for further exploration. BCV offers a promising opportunity for biosecurity against OPXV-based bioterrorism attacks and to control the MPX outbreak of 2022.
The Modulatory Effects of Fatty Acids on Cancer Progression
Authors: Westheim Annemarie J. F. , Stoffels Lara M. , Dubois Ludwig J. , van Bergenhenegouwen Jeroen , van Helvoort Ardy , Langen Ramon C. J. , Shiri-Sverdlov Ronit , Theys Jan
Published: January 2023

Cancer is the second leading cause of death worldwide and the global cancer burden rises rapidly. The risk factors for cancer development can often be attributed to lifestyle factors, of which an unhealthy diet is a major contributor. Dietary fat is an important macronutrient and therefore a crucial part of a well-balanced and healthy diet, but it is still unclear which specific fatty acids contribute to a healthy and well-balanced diet in the context of cancer risk and prognosis. In this review, we describe epidemiological evidence on the associations between the intake of different classes of fatty acids and the risk of developing cancer, and we provide preclinical evidence on how specific fatty acids can act on tumor cells, thereby modulating tumor progression and metastasis. Moreover, the pro- and anti-inflammatory effects of each of the different groups of fatty acids will be discussed specifically in the context of inflammation-induced cancer progression and we will highlight challenges as well as opportunities for successful application of fatty acid tailored nutritional interventions in the clinic.
A Portable Wireless Intelligent Nanosensor for 6,7-Dihydroxycoumarin Analysis with A Black Phosphorene and Nano-Diamond Nanocomposite-Modified Electrode
Authors: Li Xiaoqing , Wang Lisi , Yan Lijun , Han Xiao , Zhang Zejun , Zhang Xiaoping , Sun Wei
Published: January 2023

In this work, a novel portable and wireless intelligent electrochemical nanosensor was developed for the detection of 6,7-dihydroxycoumarin (6,7-DHC) using a modified screen-printed electrode (SPE). Black phosphorene (BP) nanosheets were prepared via exfoliation of black phosphorus nanoplates. The BP nanosheets were then mixed with nano-diamond (ND) to prepare ND@BP nanocomposites using the self-assembly method, achieving high environmental stability. The nanocomposite was characterized by SEM, TEM, Raman, XPS and XRD. The nanocomposite was used for the modification of SPE to improve its electrochemical performances. The nanosensor displayed a wide linear range of 0.01–450.0 μmol/L with a low detection limit of 0.003 μmol/L for 6,7-DHC analysis. The portable and wireless intelligent electrochemical nanosensor was applied to detect 6,7-DHC in real drug samples by the standard addition method with satisfactory recoveries, which extends the application of BP-based nanocomposite for electroanalysis.