bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison of Bone Segmentation Software over Different Anatomical Parts
Authors: Belvedere Claudio , Ortolani Maurizio , Marcelli Emanuela , Bortolani Barbara , Matsiushevich Katsiaryna , Durante Stefano , Cercenelli Laura , Leardini Alberto
Published: June 2022

Three-dimensional bone shape reconstruction is a fundamental step for any subject-specific musculo-skeletal model. Typically, medical images are processed to reconstruct bone surfaces via slice-by-slice contour identification. Freeware software packages are available, but commercial ones must be used for the necessary certification in clinics. The commercial software packages also imply expensive hardware and demanding training, but offer valuable tools. The aim of the present work is to report the performance of five commercial software packages (Mimics®, AmiraTM, D2PTM, SimplewareTM, and Segment 3D PrintTM), particularly the time to import and to create the model, the number of triangles of the mesh, and the STL file size. DICOM files of three different computed tomography scans from five different human anatomical areas were utilized for bone shape reconstruction by using each of these packages. The same operator and the same hosting hardware were used for these analyses. The computational time was found to be different between the packages analyzed, probably because of the pre-processing implied in this operation. The longer “time-to-import” observed in one software is likely due to the volume rendering during uploading. A similar number of triangles per megabyte (approximately 20 thousand) was observed for the five commercial packages. The present work showed the good performance of these software packages, with the main features being better than those analyzed previously in freeware packages.
Mining Algorithm of Relatively Important Nodes Based on Edge Importance Greedy Strategy
Authors: Li Jie , Yin Chunlin , Wang Hao , Wang Jian , Zhao Na
Published: June 2022

Relatively important node mining has always been an essential research topic in complex networks. Existing relatively important node mining algorithms suffer from high time complexity and poor accuracy. Therefore, this paper proposes an algorithm for mining relatively important nodes based on the edge importance greedy strategy (EG). This method considers the importance of the edge to represent the degree of association between two connected nodes. Therefore, the greater the value of the connection between a node and a known important node, the more likely it is to be an important node. If the importance of the edges in an undirected network is measured, a greedy strategy can find important nodes. Compared with other relatively important node mining methods on real network data sets, such as SARS and 9/11, the experimental results show that the EG algorithm excels in both accuracy and applicability, which makes it a competitive algorithm in the mining of important nodes in a network.
Solvents for Membrane-Based Post-Combustion CO2 Capture for Potential Application in the Marine Environment
Authors: Damartzis Theodoros , Asimakopoulou Akrivi , Koutsonikolas Dimitrios , Skevis George , Georgopoulou Chara , Dimopoulos George , Nikolopoulos Lampros , Bougiouris Konstantinos , Richter Hannes , Lubenau Udo , Economopoulos Solon , Perinu Cristina , Hopkinson David , Panagakos Grigorios
Published: June 2022

Carbon capture on-board ships represents a powerful technological measure in order for the shipping industry to meet the very stringent GHG emission reduction requirements. Operation within the ship environment introduces a number of constraints associated mainly with space, energy supply, and safety which have to be addressed using compact yet efficient solutions. To this end, solvent-based membrane CO2 capture offers several advantages and has the necessary technological maturity for on-board installation. Solvent choice remains a critical issue both for reasons associated with process efficiency as well as on-board safety. In this paper, we present an up-to-date comprehensive review of the different solvents that can be used for post-combustion CO2 capture. Furthermore, we investigated the solvents’ performance as determined by their inherent characteristics, properties, and behavior for a range of operating conditions against the strict shipping requirements. A preliminary qualitative comparative assessment was carried out based on appropriately selected key performance indicators (KPIs) pertinent to the requirements of the shipping industry. The identified solvent classes were compared using the most critical KPIs for system integration with the ship. It was concluded that at present, no solvent category can efficiently address all the requirements of the ship. However, widely used solvents such as secondary amines showed relatively good compatibility with the majority of the introduced KPIs. On the other hand, more recently developed molecules, such as phase change solvents and ionic liquids, can easily prevail over the vast majority of the identified solvents as long as they are brought to the same level of technological maturity with benchmark solvents. Such a conclusion points toward the need for accelerating research on more tailor-made and performance-targeted solvents.
A Validated HPLC-MS/MS Method for Quantification of Fingolimod and Fingolimod-Phosphate in Human Plasma: Application to Patients with Relapsing–Remitting Multiple Sclerosis
Authors: Fracasso Claudia , Passoni Alice , Brambilla Laura , Mantegazza Renato , Rossi Silvia , Gobbi Marco , Lucchetti Jacopo
Published: June 2022

Fingolimod is a sphingosine 1-phosphate-receptor modulator approved for the oral treatment of relapsing–remitting multiple sclerosis (RRMS), a form of MS characterized by a pattern of exacerbation of neurological symptoms followed by recovery. Here, we validated a simple and rapid liquid chromatography–tandem mass spectrometry method for the measurement of the concentrations of Fingolimod and its active metabolite Fingolimod-Phosphate (Fingolimod-P) in human plasma. The lower limits of quantification were set at 0.3 and 1.5 ng/mL for Fingolimod and Fingolimod-P, respectively, and the linearity was in the range 0.3–150 ng Fingolimod/mL and 1.5–150 ng Fingolimod-P/mL. After protein precipitation, the extraction recoveries of both analytes were always above 60% with minimal matrix effect. The method was accurate and precise, satisfying the criteria set in the European Medicine Agency guidelines for bioanalytical method validation. The method was then applied to measure Fingolimod and Fingolimod-P concentrations in the plasma of 15 RRMS patients under chronic treatment with Fingolimod, administered daily at the dose of 0.5 mg for up to 24 months. No significant differences were observed between samples collected at 6, 12 and 24 months for both analytes, indicating that the drug’s bioavailability was unaffected by multiple daily doses up to 24 months. The levels of Fingolimod-P were about two-fold higher than the levels of the parent compound. The availability of this analytical method can allow the monitoring of the impact of plasma levels of the drug and its metabolite on inter-individual variability in clinical responses.
Hygroscopic Ground-Based Generator Cloud Seeding Design; A Case Study from the 2020 Weather Modification in Larona Basin Indonesia
Authors: Renggono Findy , Kudsy Mahally , Adhitya Krisna , Purwadi Purwadi , Belgaman Halda Aditya , Dewi Saraswati , Syahdiza Rahmawati , Mulyana Erwin , Aldrian Edvin , Arifian Jon
Published: June 2022

Cloud seeding activities have been carried out in the form of experiments and operation activities as part of water resource management in some parts of the world. Recently, a new method of cloud seeding using a ground-based generator (GBG) was introduced in Indonesia. This method is used to seed orographic clouds with the aid of a 50 m GBG tower located in a mountainous area. By taking advantage of the topography and local circulation, the GBG tower will introduce hygroscopic seeding materials into orographic clouds to accelerate the collision and coalescence process within the clouds, increasing the cloud’s rainfall amount. The hygroscopic ground-based cloud seeding was conducted over the Larona Basin in Sulawesi, Indonesia, from December 2019 to April 2020. There were five towers installed around Larona Basin, located over 500 m above sea level. The results show that there was an increase in monthly rainfall amount from the GBG operation period in January, February, and March compared to its long-term average of as much as 79%, 17%, and 46%, respectively. Meanwhile, despite an increase of 0.4% in Lake Towuti water level, it is still not concluded that the GBG cloud seeding operation was involved in the lake water level raise. Therefore, more studies need to be performed in the future to answer whether the cloud seeding affected the lake water level.
Characterization of Imidazole Compounds in Aqueous Secondary Organic Aerosol Generated from Evaporation of Droplets Containing Pyruvaldehyde and Inorganic Ammonium
Authors: Lin Xin , Huang Mingqiang , Lu Tingting , Zhao Weixiong , Hu Changjin , Gu Xuejun , Zhang Weijun
Published: June 2022

Imidazole compounds are important constituents of atmospheric brown carbon. The imidazole components of aqueous secondary organic aerosol (aqSOA) that are generated from the evaporation of droplets containing pyruvaldehyde and inorganic ammonium are on-line characterized by an aerosol laser time-of-flight mass spectrometer (ALTOFMS) and off-line detected by optical spectrometry in this study. The results demonstrated that the laser desorption/ionization mass spectra of aqSOA particles that were detected by ALTOFMS contained the characteristic mass peaks of imidazoles at m/z = 28 (CH2N+), m/z = 41 (C2H3N+) and m/z = 67 (C3H4N2+). Meanwhile, the extraction solution of the aqSOA particles that were measured by off-line techniques showed that the characteristic absorption peaks at 217 nm and 282 nm appeared in the UV-Vis spectrum, and the stretching vibration peaks of C-N bond and C=N bond emerged in the infrared spectrum. Based on these spectral information, 4-methyl-imidazole and 4-methyl-imidazole-2-carboxaldehyde are identified as the main products of the reaction between pyruvaldehyde and ammonium ions. The water evaporation accelerates the formation of imidazoles inside the droplets, possibly owing to the highly concentrated environment. Anions, such as F−, CO32−, NO3−, SO42− and Cl− in the aqueous phase promote the reaction of pyruvaldehyde and ammonium ions to produce imidazole products, resulting in the averaged mass absorption coefficient () in the range of 200–600 nm of aqSOA increases, and the order of promotion is: F− > CO32− > SO42− ≈ NO3− ≈ Cl−. These results will help to analyze the constituents and optics of imidazoles and provide a useful basis for evaluating the formation process and radiative forcing of aqSOA particles.
Topographical and Thermal Forcing in Favorable Circulation Pattern to Early Spring Precipitation over the Southeastern Tibetan Plateau
Authors: Yang Yaoxian , Hu Zeyong , Li Maoshan , Yu Haipeng , Ma Weiqiang , Fan Weiwei
Published: June 2022

During the boreal spring (March–May), the precipitation that occurs from March over the southeastern Tibetan Plateau (TP) can account for 20–40% of the total annual amount. The origin of this phenomenon has not been clearly understood from a climatological perspective. In this study, the role of topographical and thermal forcing on the precipitation over the southeastern TP in early spring (March) was investigated through sensitivity numerical simulations based on general circulation model. The simulated results show the favorable circulation and static stability to early spring precipitation over the southeastern TP when the model is simultaneously forced by realistic topography, zonal symmetric radiative equilibrium temperature, and diabatic heating over the TP and its surrounding areas. The quasi-stationary wave pattern over the Eurasian continent forced by realistic and TP topographical forcing leads to prolonged low pressure and intensified zonal winds over the southeastern TP due to quasi-steady wave activities. Thermal forcing experiments reveals that sensible heating over the southeastern TP not only strengthens the cyclonic circulation, ascending motion and statically unstable over the southeastern TP through thermal adaptation and the Sverdrup balance, but also triggers an anticyclone at upper tropospheric level extending from north of the Bay of Bengal to the eastern TP, which further favors precipitation over the southeastern TP. This work will provide useful background information for spring climate prediction over the TP.
Multitask Learning Based on Least Squares Support Vector Regression for Stock Forecast
Authors: Zhang Heng-Chang , Wu Qing , Li Fei-Yan , Li Hong
Published: June 2022

Various factors make stock market forecasting difficult and arduous. Single-task learning models fail to achieve good results because they ignore the correlation between multiple related tasks. Multitask learning methods can capture the cross-correlation among subtasks and achieve a satisfactory learning effect by training all tasks simultaneously. With this motivation, we assume that the related tasks are close enough to share a common model whereas having their own independent models. Based on this hypothesis, we propose a multitask learning least squares support vector regression (MTL-LS-SVR) algorithm, and an extension, EMTL-LS-SVR. Theoretical analysis shows that these models can be converted to linear systems. A Krylov-Cholesky algorithm is introduced to determine the optimal solutions of the models. We tested the proposed models by applying them to forecasts of the Chinese stock market index trend and the stock prices of five stated-owned banks. The experimental results demonstrate their validity.
Efficiency of the Adjusted Binary Classification (ABC) Approach in Osteometric Sex Estimation: A Comparative Study of Different Linear Machine Learning Algorithms and Training Sample Sizes
Authors: Attia MennattAllah Hassan , Kholief Marwa A. , Zaghloul Nancy M. , Kružić Ivana , Anđelinović Šimun , Bašić Željana , Jerković Ivan
Published: June 2022

The adjusted binary classification (ABC) approach was proposed to assure that the binary classification model reaches a particular accuracy level. The present study evaluated the ABC for osteometric sex classification using multiple machine learning (ML) techniques: linear discriminant analysis (LDA), boosted generalized linear model (GLMB), support vector machine (SVM), and logistic regression (LR). We used 13 femoral measurements of 300 individuals from a modern Turkish population sample and split data into two sets: training (n = 240) and testing (n = 60). Then, the five best-performing measurements were selected for training univariate models, while pools of these variables were used for the multivariable models. ML classifier type did not affect the performance of unadjusted models. The accuracy of univariate models was 82–87%, while that of multivariate models was 89–90%. After applying ABC to the crossvalidation set, the accuracy and the positive and negative predictive values for uni- and multivariate models were ≥95%. Sex could be estimated for 28–75% of individuals using univariate models but with an obvious sexing bias, likely caused by different degrees of sexual dimorphism and between-group overlap. However, using multivariate models, we minimized the bias and properly classified 81–87% of individuals. A similar performance was also noted in the testing sample (except for FEB), with accuracies of 96–100%, and a proportion of classified individuals between 30% and 82% in univariate models, and between 90% and 91% in multivariate models. When considering different training sample sizes, we demonstrated that LR was the most sensitive with limited sample sizes (n < 150), while GLMB was the most stable classifier.
Microbial Consortia: An Engineering Tool to Suppress Clubroot of Chinese Cabbage by Changing the Rhizosphere Bacterial Community Composition
Authors: Zhang Jinhao , Ahmed Waqar , Dai Zhenlin , Zhou Xinghai , He Zulei , Wei Lanfang , Ji Guanghai
Published: June 2022

Clubroot disease, caused by Plasmodiophora brassicae, is a serious threat to Chinese cabbage (Brassica rapa subsp. pekinensis) production, which results in extensive yield losses. At present, clubroot control mainly depends upon pesticides, which provoke food-safety concerns, and the application of sole biocontrol agents cannot successfully control the disease. In this study, we investigated the effect of Bacillus cereus BT-23, Lysobacter antibioticus 13-6, and Lysobacter capsici ZST1-2 as sole strains, intra-/inter-genus co-culture, and microbial consortia on clubroot disease, plant growth, and rhizosphere bacterial diversity in a field experiment. The microbial consortia efficiently controlled the incidence of clubroot disease, with a biocontrol effect of about 65.78%, by decreasing the soil acidity and enhancing the yield (17,662.49 kg/acre). The high-throughput sequencing results demonstrated that the phyla Proteobacteria and Bacteroidetes were present in high relative abundance in the rhizosphere soil of the Chinese cabbage. Furthermore, Firmicutes was found as a unique phylum in the rhizosphere soil of CK-H and T1-T7, except for CK-D. The application of microbial consortia recovers the imbalance in indigenous microbial communities. Therefore, we conclude that microbial consortia can reduce the clubroot incidence in Chinese cabbage by decreasing the soil acidity and altering the diversity and structure of rhizosphere bacterial communities. This study highlights the potential of microbial consortia as an engineering tool to control devastating soilborne diseases in commercial crops.
Effect of Nitric Oxide Pathway Inhibition on the Evolution of Anaphylactic Shock in Animal Models: A Systematic Review
Authors: Alfalasi Maryam , Alzaabi Sarah , Östlundh Linda , Al-Rifai Rami H. , Al-Salam Suhail , Mertes Paul Michel , Alper Seth L. , Aburawi Elhadi H. , Bellou Abdelouahab
Published: June 2022

Nitric oxide (NO) induces vasodilation in various types of shock. The effect of pharmacological modulation of the NO pathway in anaphylactic shock (AS) remains poorly understood. Our objective was to assess, through a systematic review, whether inhibition of NO pathways (INOP) was beneficial for the prevention and/or treatment of AS. A predesigned protocol for this systematic review was published in PROSPERO (CRD42019132273). A systematic literature search was conducted till March 2022 in the electronic databases PubMed, EMBASE, Scopus, Cochrane and Web of Science. Heterogeneity of the studies did not allow meta-analysis. Nine hundred ninety unique studies were identified. Of 135 studies screened in full text, 17 were included in the review. Among six inhibitors of NO pathways identified, four blocked NO synthase activity and two blocked guanylate cyclase downstream activity. Pre-treatment was used in nine studies and post-treatment in three studies. Five studies included both pre-treatment and post-treatment models. Overall, seven pre-treatment studies from fourteen showed improvement of survival and/or arterial blood pressure. Four post-treatment studies from eight showed positive outcomes. Overall, there was no strong evidence to conclude that isolated blockade of the NO/cGMP pathway is sufficient to prevent or restore anaphylactic hypotension. Further studies are needed to analyze the effect of drug combinations in the treatment of AS.
Morphometric Features and Microanatomy of the Lingual Filiform Papillae in the Wistar Rat
Authors: Huțanu Elena , Damian Aurel , Miclăuș Viorel , Rațiu Ioana A. , Rus Vasile , Vlasiuc Ion , Gal Adrian F.
Published: June 2022

The mammalian tongue plays a fundamental role in various physiological and behavioral activities. Significant morphological variations have been recorded in the tongue of several species. This study aims to obtain detailed histological and morphometric information about the filiform papillae on the surface of rat tongue. The tongues of five 10-month-old Wistar rats were utilized, which were later examined with a stereo-microscope. Fragments from the three regions of the tongue were collected for histological investigations. The tongue of the Wistar rat has an intensely keratinized stratified squamous epithelium, with the highest degree of keratinized epithelium covering the filiform papillae. The filiform papillae differ in density, with the highest density recorded on the posterior part of the lingual body and the lowest density on the protuberance. The shortest filiform papillae were observed on the apex of the tongue and the tallest on the anterior part of the lingual body. Interestingly, the orientation of the filiform papillae on the lingual protuberance was inclined posteroanteriorly, in the opposite way as compared to the papillae from all the other regions of the tongue. Histologically, a difference was recorded in the structure of the covering epithelium of the anterior vs. the posterior face of the filiform papillae.
Spatiotemporal Coupling of DNA Supercoiling and Genomic Sequence Organization—A Timing Chain for the Bacterial Growth Cycle?
Authors: Muskhelishvili Georgi , Sobetzko Patrick , Travers Andrew
Published: June 2022

In this article we describe the bacterial growth cycle as a closed, self-reproducing, or autopoietic circuit, reestablishing the physiological state of stationary cells initially inoculated in the growth medium. In batch culture, this process of self-reproduction is associated with the gradual decline in available metabolic energy and corresponding change in the physiological state of the population as a function of “travelled distance” along the autopoietic path. We argue that this directional alteration of cell physiology is both reflected in and supported by sequential gene expression along the chromosomal OriC-Ter axis. We propose that during the E. coli growth cycle, the spatiotemporal order of gene expression is established by coupling the temporal gradient of supercoiling energy to the spatial gradient of DNA thermodynamic stability along the chromosomal OriC-Ter axis.
Association between Vitamin D Receptor Gene Polymorphisms and Periodontal Bacteria: A Clinical Pilot Study
Authors: Cafiero Concetta , Grippaudo Cristina , Dell’Aquila Marco , Cimmino Pasquale , D’Addona Antonio , De Angelis Paolo , Ottaiano Maria Pia , Costagliola Domenico , Benincasa Giulio , Micera Alessandra , Santacroce Luigi , Palmirotta Raffaele
Published: June 2022

Background: Periodontitis is an inflammatory disease caused by microorganisms involving the supporting tissues of the teeth. Gene variants may influence both the composition of the biofilm in the oral cavity and the host response. The objective of the study was to investigate the potential correlations between the disease susceptibility, the presence and the quantity of periodontopathogenic oral bacterial composition and the VDR gene polymorphisms. Methods: Fifty (50) unrelated periodontal patients and forty-one (41) healthy controls were selected for genomic DNA extraction. DNA concentration was measured and analyzed. The periodontopathogenic bacterial species were identified and quantified using a Real Time PCR performed with species-specific primers and probes. Results: Genotype distribution showed a different distribution between the groups for BsmI rs1544410 genotypes (p = 0.0001) with a prevalence of the G(b) allele in periodontal patients (p = 0.0003). Statistical significance was also found for VDR TaqI rs731236 (p ≤ 0.00001) with a prevalence of the T(T) allele in periodontal patients (p ≤ 0.00001). The average bacterial copy count for the periodontitis group was significantly higher than that of control group. Dividing patients into two groups based on high or low bacterial load, FokI rs2228570 T allele (f) was statistically more represented in patients with high bacterial load. Conclusions: The findings of the study suggest the involvement of the VDR gene BsmI and TaqI polymorphisms in periodontal disease, while FokI and BsmI may be involved in determining an increased presence of periodontopathogens.
Assessing the Capability of Government Information Intervention and Socioeconomic Factors of Information Sharing during the COVID-19 Pandemic: A Cross-Country Study Using Big Data Analytics
Authors: Park Sejung , Wang Rong
Published: June 2022

(1) Background: This study introduces a novel computational approach to examine government capabilities in information intervention for risk management, influential agents in a global information network, and the socioeconomic factors of information-sharing behaviors of the public across regions during the COVID-19 pandemic. (2) Methods: Citation network analysis was employed to gauge the online visibility of governmental health institutions across regions. A bipartite exponential random graph modeling (ERGM) procedure was conducted to measure network dynamics. (3) Results: COVID-19 response agencies in Europe had the highest web impact, whereas health agencies in North America had the lowest. Various stakeholders, such as businesses, non-profit organizations, governments, and educational institutions played a key role in sharing the COVID-19 response by agencies’ information given on their websites. Income inequality and GDP per capita were associated with the high online visibility of governmental health agencies. Other factors, such as population size, an aging population, death rate, and case percentage, did not contribute to the agencies’ online visibility, suggesting that demographic characteristics and health status are not predictors of sharing government resources. (4) Conclusions: A combination of citation network analysis and ERGM helps reveal information flow dynamics and understand the socioeconomic consequences of sharing the government’s COVID-19 information during the pandemic.
Collaborative Governance of Tower Crane Safety in the Chinese Construction Industry: A Social Network Perspective
Authors: Yang Ying , Shao Bo , Jin Lianghai , Zheng Xiazhong
Published: June 2022

Tower crane safety governance is an important issue related to the sustainable development of China’s construction industry. The complex collaborative relationship among stakeholders determines the efficiency of tower crane safety governance. From the perspective of social networks, this study constructs a collaborative governance structure model of tower crane safety from four dimensions, i.e., transaction, supervision, dependency, and communication, and analyzes the structural characteristics of tower crane safety collaborative governance and the mutual relationship among stakeholders. The results show that the tower crane safety governance process has a strong collaborative effect, but that collaboration in terms of supervision and communication among stakeholders is currently poor. The tower crane property owner occupies the core position, so their decisions have a great impact on tower crane safety. The power of the government is too large, and the power of supervision is too small, which affects the collaboration enthusiasm of other stakeholders, thus reducing the overall collaboration efficiency. The findings provide theoretical support for tower crane safety management in the construction industry in China. The social network perspective presented in this study can be applied to clarify relationships among stakeholders in other construction safety governance fields.
Energy Flexibility Comparison of Different Control Strategies for Zones with Radiant Floor Systems
Authors: Saberi-Derakhtenjani Ali , Athienitis Andreas K. , Eicker Ursula , Rodriguez-Ubinas Edwin
Published: June 2022

Radiant floor systems offer significant potential for studying and developing energy flexibility strategies for buildings and their interaction with smart grids. Efficient design and operation of such systems require several critical decisions on design and control variables to maintain comfortable thermal conditions in the space and floor surface temperatures within the recommended range. This study presents a comparison of different control strategies to activate energy flexibility for zones with radiant floor heating systems. The focus of this study is on the zones with radiant floor systems for which the hydronic pipes are located deep in the concrete and therefore, there is a significant thermal lag. A perimeter zone test room equipped with a hydronic radiant floor system in an environmental chamber is used as to validate the modelling methodology. Considering a typical cloudy and cold winter day, three different control strategies for radiant heating were studied based on controlling the zone air temperature, floor surface temperature, and the operative temperature. Then considering morning and evening peak demand periods, the downward and upward energy flexibility are quantified and compared with each other for the different control strategies. It is observed that for the same 2 °C increase or decrease in the setpoint, the control strategy based on the zone air temperature results in the higher flexibility for both downward and upward scenarios compared with the floor surface and operative temperature controls. The effect of increasing window to wall ratio (WWR) is also investigated. Then, also the effect of solar gains on a sunny day on energy flexibility is studied. No significant difference in the upward and downward flexibility is observed. However, the hours of zero heating load are significantly increased due to the contribution from the solar gains.
Pulsed-Reduced Dose Rate (PRDR) Radiotherapy for Recurrent Primary Central Nervous System Malignancies: Dosimetric and Clinical Results
Authors: Kutuk Tugce , Tolakanahalli Ranjini , McAllister Nicole , Hall Matthew , Tom Martin , Rubens Muni , Appel Haley , Gutierrez Alonso , Odia Yazmin , Mohler Alexander , Ahluwalia Manmeet , Mehta Minesh , Kotecha Rupesh
Published: June 2022

Purpose: The objective was to describe PRDR outcomes and report EQD2 OAR toxicity thresholds. Methods: Eighteen patients with recurrent primary CNS tumors treated with PRDR at a single institution between April 2017 and September 2021 were evaluated. The radiotherapy details, cumulative OAR doses, progression-free survival (PFS), overall survival (OS), and toxicities were collected. Results: The median PRDR dose was 45 Gy (range: 36–59.4 Gy); the median cumulative EQD2 prescription dose was 102.7 Gy (range: 93.8–120.4 Gy). The median cumulative EQD2 D0.03cc for the brain was 111.4 Gy (range: 82.4–175.2 Gy). Symptomatic radiation necrosis occurred in three patients, for which the median EQD2 brain D0.03cc was 115.9 Gy (110.4–156.7 Gy). The median PFS and OS after PRDR were 6.3 months (95%CI: 0.9–11.6 months) and 8.6 months (95%CI: 4.9–12.3 months), respectively. The systematic review identified five peer-reviewed studies with a median cumulative EQD2 prescription dose of 110.3 Gy. At a median follow-up of 8.7 months, the median PFS and OS were 5.7 months (95%CI: 2.1–15.4 months) and 6.7 months (95%CI: 3.2–14.2 months), respectively. Conclusion: PRDR re-irradiation is a relatively safe and feasible treatment for recurrent primary CNS tumors. Despite high cumulative dose to OARs, the risk of high-grade, treatment-related toxicity within the first year of follow-up remains acceptable.
Multiple Components of Protein Homeostasis Pathway Can Be Targeted to Produce Drug Synergies with VCP Inhibitors in Ovarian Cancer
Authors: Bastola Prabhakar , Leiserowitz Gary S. , Chien Jeremy
Published: June 2022

Protein quality control mechanisms play an important role in cancer progression by providing adaptive responses and morphologic stability against genome-wide copy number alterations, aneuploidy, and conformation-altering somatic mutations. This dependency on protein quality control mechanisms creates a vulnerability that may be exploited for therapeutic benefits by targeting components of the protein quality control mechanism. Recently, valosin-containing protein (VCP), also known at p97 AAA-ATPase, has emerged as a druggable target in cancer cells to affect their dependency on protein quality control. Here, we show that VCP inhibitors induce cytotoxicity in several ovarian cancer cell lines and these compounds act synergistically with mifepristone, a drug previously shown to induce an atypical unfolded protein response. Although mifepristone at a clinically achievable dose induces a weak unfolded protein response, it enhances the cytotoxic effects of VCP inhibitor CB-5083. Mechanistically, mifepristone blocks the cytoprotective effect of ATF6 in response to endoplasmic reticulum (ER) stress while activating the cytotoxic effects of ATF4 and CHOP through the HRI (EIF2AK1)-mediated signal transduction pathway. In contrast, CB-5083 activates ATF4 and CHOP through the PERK (EIF2AK3)-mediated signaling pathway. This combination activates ATF4 and CHOP while blocking the adaptive response provided by ATF6, resulting in increased cytotoxic effects and synergistic drug interaction.
Gastric Cancer-Derived Extracellular Vesicles (EVs) Promote Angiogenesis via Angiopoietin-2
Authors: Kalfon Talya , Loewenstein Shelly , Gerstenhaber Fabian , Leibou Stav , Geller Hen , Sher Osnat , Nizri Eran , Lahat Guy
Published: June 2022

Angiogenesis is an important control point of gastric cancer (GC) progression and metastasis. Angiopoietin-2 (ANG2) is a key driver of tumor angiogenesis and metastasis, and it has been identified in primary GC tissues. Extracellular vesicles (EVs) play an important role in mediating intercellular communication through the transfer of proteins between cells. However, the expression of ANG2 in GC-EVs has never been reported. Here, we characterized the EV-mediated crosstalk between GC and endothelial cells (ECs), with particular focus on the role of ANG2. We first demonstrate that ANG2 is expressed in GC primary and metastatic tissues. We then isolated EVs from two different GC cell lines and showed that these EVs enhance EC proliferation, migration, invasion, and tube formation in vitro and in vivo. Using an angiogenesis protein array, we showed that GC-EVs contain high levels of proangiogenic proteins, including ANG2. Lastly, using Lenti viral ANG2-shRNA, we demonstrated that the proangiogenic effects of the GC-EVs were mediated by ANG2 through the activation of the PI3K/Akt signal transduction pathway. Our data suggest a new mechanism via which GC cells induce angiogenesis. This knowledge may be utilized to develop new therapies in gastric cancer.
The Molecular Basis and Therapeutic Potential of Leukemia Inhibitory Factor in Cancer Cachexia
Authors: Zeng Ruijiang , Tong Chang , Xiong Xiangyang
Published: June 2022

Cachexia is a chronic metabolic syndrome that is characterized by sustained weight and muscle mass loss and anorexia. Cachexia can be secondary to a variety of diseases and affects the prognosis of patients significantly. The increase in inflammatory cytokines in plasma is deeply related to the occurrence of cachexia. As a member of the IL-6 cytokine family, leukemia inhibitory factor (LIF) exerts multiple biological functions. LIF is over-expressed in the cancer cells and stromal cells of various tumors, promoting the malignant development of tumors via the autocrine and paracrine systems. Intriguingly, increasing studies have confirmed that LIF contributes to the progression of cachexia, especially in patients with metastatic tumors. This review combines all of the evidence to summarize the mechanism of LIF-induced cachexia from the following four aspects: (i) LIF and cancer-associated cachexia, (ii) LIF and alterations of adipose tissue in cachexia, (iii) LIF and anorexia nervosa in cachexia, and (iv) LIF and muscle atrophy in cachexia. Considering the complex mechanisms in cachexia, we also focus on the interactions between LIF and other key cytokines in cachexia and existing therapeutics targeting LIF.
NR2F1, a Tumor Dormancy Marker, Is Expressed Predominantly in Cancer-Associated Fibroblasts and Is Associated with Suppressed Breast Cancer Cell Proliferation
Authors: Wu Rongrong , Roy Arya , Tokumaru Yoshihisa , Gandhi Shipra , Asaoka Mariko , Oshi Masanori , Yan Li , Ishikawa Takashi , Takabe Kazuaki
Published: June 2022

Background: Tumor dormancy is a crucial mechanism responsible for the late recurrence of breast cancer. Thus, we investigated the clinical relevance of the expression of NR2F1, a known dormancy biomarker. Methods: A total of 6758 transcriptomes of bulk tumors from multiple breast cancer patient cohorts and two single-cell sequence cohorts were analyzed. Results: Breast cancer (BC) with high NR2F1 expression enriched TGFβ signaling, multiple metastases, and stem cell-related pathways. Cell proliferation-related gene sets were suppressed, and MKi67 expression was lower in high NR2F1 BC. In tumors with high Nottingham grade, NR2F1 expression was found to be lower. There was no consistent relationship between NR2F1 expression and metastasis or survival. Cancer mutation rates, immune responses, and immune cell infiltrations were lower in high NR2F1 tumors, whereas the infiltration of stromal cells including cancer-associated fibroblasts (CAFs) was higher. NR2F1 was predominantly expressed in CAFs, particularly inflammatory CAFs, rather than in cancer cells, consistently in the two single-cell sequence cohorts. Conclusions: NR2F1 expression in breast cancer is associated with tumor dormancy traits, and it is predominantly expressed in CAFs in the tumor microenvironment.
Multiple Myeloma: Possible Cure from the Sea
Authors: Capalbo Anita , Lauritano Chiara
Published: June 2022

Multiple myeloma (MM) is a blood cancer that occurs in the plasma cells (PCs), a type of white blood cell. Despite the progress of several current treatments that prolong the overall patient’s survival, most MM cases are incurable. For this reason, many efforts have been undertaken by the scientific community in the search for new treatments. BLENREPTM and Aplidin® are two marine-derived drugs currently in use for MM. In addition, other natural products have been identified from marine organisms, tested for their possible anticancer properties, and are in preclinical or clinical trials for MM, including cytarabine, a compound in use for leukaemia treatment. Between the most successful marine compounds in fighting MM, there are molecules with specific targets, such as the elongation factor 1-alpha 2 and proteasome inhibitors, and compounds conjugated with antibodies that recognise specific cell types and direct the drug to the correct cell target. Active compounds belong to different chemical classes, from cyclic peptides to alkaloids, highlighting the importance of screening the plethora of compounds produced by marine organisms. In this review, we summarise the current state of art of MM therapies focusing on the marine natural product emerging roles.
Iridium(triNHC)-Catalyzed Transfer Hydrogenation of Glycerol Carbonate without Exogenous Reductants
Authors: Cheong Yeon-Joo , Lee Mi-hyun , Byeon Heemin , Park Jiyong , Yu Sungju , Jang Hye-Young
Published: June 2022

The iridium(Ir) (triNHC = tri-N-heterocyclic carbene)-catalyzed transfer hydrogenation of glycerol carbonate (GC) is described in the absence of additional hydride sources. The described reduction provides a sustainable route to produce industrially-valuable formate and lactate with high turnover numbers (TONs). The bimetallic Ir(I) involving triNHC carbene ligands exhibits high TONs, and the reaction mechanism, including the bimetallic Ir(triNHC) catalyst, is proposed based on mechanistic studies.
Recent Developments in Nanocatalyzed Green Synthetic Protocols of Biologically Potent Diverse O-Heterocycles—A Review
Authors: Kumar Suresh , Saroha Bhavna , Kumar Gourav , Lathwal Ekta , Kumar Sanjeev , Parshad Badri , Kumari Meena , Kumar Naveen , Mphahlele-Makgwane Mabel M. , Makgwane Peter R.
Published: June 2022

The dynamic growth in green organic synthetic methodologies for diverse heterocyclic scaffolds has substantially contributed to the field of medicinal chemistry over the last few decades. The use of hybrid metal nanocatalysts (NCs) is one such benign strategy for ensuring the advancement of modern synthetic chemistry by adhering to the principles of green chemistry, which call for a sustainable catalytic system that converts reacting species into profitable chemicals at a faster rate and tends to reduce waste generation. The metal nanoparticles (NPs) enhance the exposed surface area of the catalytic active sites, thereby making it easier for reactants and metal NCs to have an effective interaction. Several review articles have been published on the preparation of metal NCs and their uses for various catalytic heterocyclic transformations. This review will summarize different metal NCs for the efficient green synthesis of various O-heterocycles. Furthermore, the review will provide a concise overview of the role of metal NCs in the synthesis of O-heterocycles and will be extremely useful to researchers working on developing novel green and simple synthetic pathways to various O-heterocyclic-derived molecules.
Tunable Coefficient of Thermal Expansion of Composite Materials for Thin-Film Coatings
Authors: Long Xu , Su Tianxiong , Chen Zubin , Su Yutai , Siow Kim S.
Published: June 2022

In most engineering applications, the coefficients of thermal expansion (CTEs) of different materials in integrated structures are inconsistent, especially for the thin-film multilayered coatings. Therefore, mismatched thermal deformation is induced due to temperature variation, which leads to an extreme temperature gradient, stress concentration, and damage accumulation. Controlling the CTEs of materials can effectively eliminate the thermally induced stress within the layered structures and thus considerably improve the mechanical reliability and service life. In this paper, randomly distributed fibers are incorporated into the matrix material and thus utilized to tune the material CTE from the macroscopical viewpoint. To this end, finite element (FE) modeling is proposed for fiber-reinforced matrix composites. In order to overcome the challenges of creating numerical models at a mesoscale, the random distribution of fibers in three-dimensional space is realized by proposing a fiber growth algorithm with the control of the in-plane and out-of-plane angles of fibers. The homogenization method is adopted to facilitate the FE simulations by using the representative volume element (RVE) of composite materials. Periodic boundary conditions (PBC) are applied to realize the prediction of the equivalent CTE of macroscopic composite materials with randomly distributed fibers. In the established FE model, the random distribution of carbon fibers in the matrix makes it possible to tune the CTE of the composite material by considering the orientation of fibers in the matrix. The FE predictions show that the volume fraction of carbon fibers in the composite materials is found to be crucial to macroscopic CTE, but results in minor variations in Young’s modulus and shear modulus. With the developed ABAQUS plug-in program, the proposed tuning method for CTE is promising to be standardized for industrial practice.
Design and Analysis of Biomedical Scaffolds Using TPMS-Based Porous Structures Inspired from Additive Manufacturing
Authors: Verma Rati , Kumar Jitendra , Singh Nishant Kumar , Rai Sanjay Kumar , Saxena Kuldeep K. , Xu Jinyang
Published: June 2022

Gyroid (G) and primitive (P) porous structures have multiple application areas, ranging from thermal to mechanical, and fall in the complex triply periodic minimal surface (TPMS) category. Such intricate bioinspired constructs are gaining attention because they meet both biological and mechanical requirements for osseous reconstruction. The study aimed to develop G and P structures with varying porosity levels from 40% to 80% by modulating the strut thickness to proportionally resemble the stiffness of host tissue. The performance characteristics were evaluated using Ti6Al4V and important relationships between feature dimension, strut thickness, porosity, and stiffness were established. Numerical results showed that the studied porous structures could decrease stiffness from 107 GPa (stiffness of Ti6Al4V) to the range between 4.21 GPa to 29.63 GPa of varying porosities, which matches the human bone stiffness range. Furthermore, using this foundation, a subject-specific scaffold (made of P unit cells with an 80% porosity) was developed to reconstruct segmental bone defect (SBD) of the human femur, demonstrating a significant decrease in the stress shielding effect. Stress transfer on the bone surrounded by a P scaffold was compared with a solid implant which showed a net increase of stress transfer of 76% with the use of P scaffold. In the conclusion, future concerns and recommendations are suggested.
Female Healthcare Workers’ Knowledge, Attitude towards Breast Cancer, and Perceived Barriers towards Mammogram Screening: A Multicenter Study in North Saudi Arabia
Authors: Alenezi Anfal Mohammed , Thirunavukkarasu Ashokkumar , Wani Farooq Ahmed , Alenezi Hadil , Alanazi Muhannad Faleh , Alruwaili Abdulaziz Saud , Alashjaee Rasha Harbi , Alashjaee Faisal Harbi , Alrasheed Abdulaziz Khalid , Alshrari Bandar Dhaher
Published: June 2022

Breast cancer is the most commonly diagnosed cancer among women in the Kingdom of Saudi Arabia and other Middle East countries. This analytical cross-sectional study assessed knowledge, attitude towards breast cancer, and barriers to mammogram screening among 414 randomly selected female healthcare workers from multiple healthcare facilities in northern Saudi Arabia. Of the studied population, 48.6% had low knowledge, and 16.1% had a low attitude towards breast cancer risk factors and symptoms. The common barriers to mammogram screening were fear to discover cancer (57.2%) and apprehension regarding radiation exposure (57%). Logistic regression analysis found that lack of awareness regarding mammogram was significantly associated with age (p = 0.030) and healthcare workers category (ref: physicians: p = 0.016). In addition, we found a significant negative correlation between knowledge and barrier scores (Spearman’s rho: −0.315, p < 0.001). It is recommended to develop target-oriented educational programs for the healthcare workers, which would empower them to educate the community regarding the risk factors and the importance of mammogram screening. Furthermore, a prospective study is warranted in other regions of the Kingdom of Saudi Arabia to understand the region-specific training needs for the healthcare workers.
Secondary (Late) Developmental Dysplasia of the Hip with Displacement: From Case Studies to a Proposition for a Modified Diagnostic Path
Authors: Dygut Jacek , Sułko Jerzy , Guevara-Lora Ibeth , Piwowar Monika
Published: June 2022

(1) Background. This paper presents a case of hip joints that were initially described as either normal or physiologically immature in four successive ultrasound examinations using the static method by Graf; however, the final treatment of the patient involved multiple hip reconstruction surgeries. (2) Case presentation. The patient was born with an Apgar score of 10 and did not exhibit neurological diseases that could deform and lead to pathological dislocation of the right hip joint. The subsequent analysis of medical data revealed that the hip luxation was due to secondary (late) developmental dysplasia of the right hip. (3) Conclusion. The article emphasizes the importance of early diagnosis and treatment standards for developmental dysplasia of the hip (DDH). The development of uniform international medical guidelines for the diagnosis, treatment, and prevention of hip dysplasia, along with the unification of DDH-related terminology, would allow for more effective management of DDH cases and reduce the cost of patient treatment.