bluuebunny/crossref_metadata_2025 huggingface dataset:
Exploring the design of a sport for employability program: A case study
Authors: Commers Tessa , Theeboom Marc , Coalter Fred
Published: October 2022

Rates of young people who are neither in employment, education, or training (NEET) are fairly high in the European Union. Correspondingly, there has been a growing tendency to regard sport as a suitable tool to develop soft skills and raise NEETs' level of employability. However, if and how such sport for employability (SfE) programs are able to realize these major claims has been called into question. The purpose of the present study was, therefore, to explore how an actual SfE initiative constructs and delivers its program. In addition, the article assessed whether the investigated program operates in line with researchers' recent calls for theory-based approaches. Guided by a case study approach set up within an initiative located in Flanders, data were gathered through 12 semi-structured interviews with 8 program providers. Results, analyzed using thematic analysis, indicated that the program was characterized by an absence of well-defined desired outcomes, imprecision as to how the program should contribute to these outcomes, and consequently minimal attention to the follow-up of participants' progress. As such, these findings and the accompanying challenges point to the absence of a theory-based approach. Several possible sources for the lack of a systematic approach are discussed.
Computational Performance Evaluation of Column Generation and Generate-and-Solve Techniques for the One-Dimensional Cutting Stock Problem
Authors: Sá Santos José Victor , Nepomuceno Napoleão
Published: October 2022

The Cutting Stock Problem (CSP) is an optimisation problem that roughly consists of cutting large objects in order to produce small items. The computational effort for solving this problem is largely affected by the number of cutting patterns. In this article, in order to cope with large instances of the One-Dimensional Cutting Stock Problem (1D-CSP), we resort to a pattern generating procedure and propose a strategy to restrict the number of patterns generated. Integer Linear Programming (ILP) models, an implementation of the Column Generation (CG) technique, and an application of the Generate-and-Solve (G&S) framework were used to obtain solutions for benchmark instances from the literature. The exact method was capable of solving small and medium sized instances of the problem. For large sized instances, the exact method was not applicable, while the effectiveness of the other methods depended on the characteristics of the instances. In general, the G&S method presented successful results, obtaining quasi-optimal solutions for the majority of the instances, by employing the strategy of artificially reducing the number of cutting patterns and by exploiting them in a heuristic framework.
Indoor Comfort and Energy Consumption Optimization Using an Inertia Weight Artificial Bee Colony Algorithm
Authors: Baharudin Farah Nur Arina , Ab. Aziz Nor Azlina , Abdul Malek Mohamad Razwan , Ghazali Anith Khairunnisa , Ibrahim Zuwairie
Published: October 2022

A comfortable indoor environment contributes to a better quality of life and wellbeing for its occupants. The indoor temperature, lighting, and air quality are the main controlling factors of user comfort levels. The optimum control of the lighting, air conditioners, and air ventilators helps in maximizing the user’s comfort level. Nonetheless, the energy consumption of these appliances needs to be taken into consideration to minimize the operational cost and at the same time provide an environmentally friendly system. Comfort level maximization and energy consumption minimization are optimization problems. This issue is becoming more important due to the lifestyle changes caused by the COVID-19 pandemic that resulted in more time spent at home and indoors. Inertia weight artificial bee colony (IW-ABC) algorithms using linearly increasing, linearly decreasing, and exponentially increasing inertia are proposed here for the optimization of the indoor comfort index and energy usage. The multi-objective problem is tackled as a weighted single objective optimization problem. The proposed solution is tested using a dataset of 48 environmental conditions. The results of the simulation show that the IW-ABC performs better than the original ABC and other benchmark algorithms and the IW-ABC with linear increasing inertia weight has the most improved convergence behavior.
Backstepping- and Sliding Mode-Based Automatic Carrier Landing System with Deck Motion Estimation and Compensation
Authors: Lungu Mihai , Chen Mou , Vîlcică (Dinu) Dana-Aurelia
Published: October 2022

This paper addresses the automatic carrier landing problem in the presence of deck motion, carrier airwake disturbance, wind shears, wind gusts, and atmospheric turbulences. By transforming the 6-DOF aircraft model into an affine dynamic with angle of attack controlled by thrust, the equations associated to the resultant disturbances are deduced; then, a deck motion prediction block (based on a recursive-least squares algorithm) and a tracking differentiator-based deck motion compensation block are designed. After obtaining the aircraft reference trajectory, the backstepping control method is employed to design a novel automatic carrier landing system with three functional parts: a guidance control system, an attitude control system, and an approach power compensation system. The design of the attitude subsystem involves the flight path control, the control of the attitude angles, and the control of the angular rates. To obtain convergence performance for the closed-loop system, the backstepping technique is combined with sliding mode-based command differentiators for the computation of the virtual commands and extended state observers for the estimation of the disturbances. The global stability of the closed-loop architecture is analyzed by using the Lyapunov theory. Finally, simulation results verify the effectiveness of the proposed carrier landing system, the aircraft reference trajectory being accurately tracked.
Usage Monitoring of Helicopter Gearboxes with ADS-B Flight Data
Authors: Hünemohr David , Litzba Jörg , Rahimi Farid
Published: October 2022

Health and usage monitoring systems (HUMS) are the basis for condition-based maintenance of helicopters. One of the most critical systems in terms of safety and maintenance expense that can be monitored by HUMS are the main gearboxes of helicopters with turbine engines. While the health monitoring part of HUMS aims to model the health state from the collected sensor data with advanced algorithms, such as machine learning, the usage monitoring part tracks the time of use and operating parameters of the system, such as load, to determine lifetime consumption. In the presented work, a combination of automatic dependent surveillance-broadcast (ADS-B) flight data with a generic helicopter performance model is used to acquire torque profiles of the gearboxes. With damage accumulation methods, the load spectra are transformed to aggregated indicators that reflect the individual gearbox usage. The methodology is applied to samples of two helicopters from a five-year ADS-B data set of German helicopter emergency medical services (HEMS) acquired for the study. The results demonstrate the feasibility of the generic approach, which can support maintenance scheduling and new usage-based maintenance services independent of direct access to installed HUMS.
New Method for Imputation of Unquantifiable Values Using Bayesian Statistics for a Mixture of Censored or Truncated Distributions: Application to Trace Elements Measured in Blood of Olive Ridley Sea Turtles from Mexico
Authors: Salvat-Leal Inmaculada , Cortés-Gómez Adriana A. , Romero Diego , Girondot Marc
Published: October 2022

One recurring difficulty in ecotoxicological studies is that a substantial portion of concentrations are below the limits of detection established by analytical laboratories. This results in censored distributions in which concentrations of some samples are only known to be below a threshold. The currently available methods have several limitations because they cannot be used with complex situations (e.g., different lower and upper limits in the same dataset, mixture of distributions, truncation and censoring in a single dataset). We propose a versatile method to fit the most diverse situations using conditional likelihood and Bayesian statistics. We test the method with a fictive dataset to ensure its correct description of a known situation. Then we apply the method to a dataset comprising 25 element concentrations analyzed in the blood of nesting marine turtles. We confirm previous findings using this dataset, and we also detect an unexpected new relationship between mortality and strontium concentration.
Bioavailability of Different Zinc Sources in Pigs 0–3 Weeks Post-Weaning
Authors: Nielsen Tina S. , Engelsmann Maiken N. , Hansen Sally V. , Maribo Hanne
Published: October 2022

The bioavailability of dietary zinc (Zn) in pigs may differ according to the Zn source and is affected by other components in the diet. The aim was to determine the biomarkers of Zn bioavailability (apparent total tract digestibility of Zn and serum Zn status) following six different sources of added Zn and their effect on the performance and faecal consistency score in piglets 0–3 weeks after weaning on day 28. The sources of Zn were Zn oxide (ZnO), Zn sulfate (ZnSO4), porous ZnO, Zn-glycinate, amino acid-bound Zn and hydroxy covalent-bound Zn added at 100 mg/kg (ZnO and ZnSO4 also added at 1000 mg/kg), in a total of eight treatments (n = 12/treatment). Pigs were individually housed, and titanium dioxide was included as an indigestible marker in the feed. The digestibility of Zn on day 14 post-weaning was negative for all six Zn sources at 100 mg Zn/kg, indicating insufficient Zn supply. The digestibility of Zn differed according to the Zn source, but the digestibility of Zn from ZnO and ZnSO4 did not differ between processed inorganic or chelated organic sources of Zn. However, the differences in Zn digestibility between Zn sources were not reflected as differences in the serum Zn status, feed intake, gain or probability of diarrhoea.
A Nonsense Variant in the DMD Gene Causes X-Linked Muscular Dystrophy in the Maine Coon Cat
Authors: Beckers Evy , Cornelis Ine , Bhatti Sofie F. M. , Smets Pascale , Shelton G. Diane , Guo Ling T. , Peelman Luc , Broeckx Bart J. G.
Published: October 2022

(1) Feline dystrophin-deficient muscular dystrophy (ddMD) is a fatal disease characterized by progressive weakness and degeneration of skeletal muscles and is caused by variants in the DMD gene. To date, only two feline causal variants have been identified. This study reports two cases of male Maine coon siblings that presented with muscular hypertrophy, growth retardation, weight loss, and vomiting. (2) Both cats were clinically examined and histopathology and immunofluorescent staining of the affected muscle was performed. DMD mRNA was sequenced to identify putative causal variants. (3) Both cats showed a significant increase in serum creatine kinase activity. Electromyography and histopathological examination of the muscle samples revealed abnormalities consistent with a dystrophic phenotype. Immunohistochemical testing revealed the absence of dystrophin, confirming the diagnosis of dystrophin-deficient muscular dystrophy. mRNA sequencing revealed a nonsense variant in exon 11 of the feline DMD gene, NC_058386.1 (XM_045050794.1): c.1180C > T (p.(Arg394*)), which results in the loss of the majority of the dystrophin protein. Perfect X-linked segregation of the variant was established in the pedigree. (4) ddMD was described for the first time in the Maine coon and the c.1180C>T variant was confirmed as the causal variant.
Automatic Movie Tag Generation System for Improving the Recommendation System
Authors: Park Hyogyeong , Yong Sungjung , You Yeonhwi , Lee Seoyoung , Moon Il-Young
Published: October 2022

As the content industry develops, the demand for movie content is increasing. Accordingly, the content industry is actively developing super-personalized recommendation systems that match consumers’ tastes. In this paper, we study automatic generation of movie tags to improve the movie recommendation system. We extracted background sounds from movie trailer videos, analyzed the sounds using STFT (Short-Time Fourier transform) and major audio attribute features, and created a genre prediction model. The experimental results show that the pre-collected dataset and the data extracted via the model are similar when compared. In this research, we suggest the methodology of an automatic genre prediction system for movie information from trailer videos. This will help to reduce the time and effort for metadata generation for a recommendation system.
Mould Growth Risks for a Clay Masonry Veneer External Wall System in a Temperate Climate
Authors: Nath Shruti , Dewsbury Mark , Künzel Hartwig , Watson Phillipa
Published: October 2022

To reduce greenhouse gas emissions, nations have introduced energy efficiency regulations for new and existing buildings. This has been considered advantageous as more efficient building envelopes would reduce energy consumed to heat and cool home interiors to within accepted thermal comfort bandwidths. However, as these methods have been adopted, many nations have identified an unintended visible presence of surface and interstitial condensation and mould in new code-compliant buildings. In Australia, it has been estimated that up to 50% of Australian houses constructed in the last decade (2006–2016) have a presence of condensation and mould. Australia introduced its first condensation and mould-related building regulations for new homes in 2019. This paper reports on the hygrothermal and mould growth analysis of the most common low-rise residential external wall system, a timber-framed clay masonry veneer wall. A key component of this paper discusses the application of innovative methods in the Australian context. The external wall’s moisture accumulation and mould growth were simulated for a period of ten years using the transient hygrothermal simulation tool, WUFI® Pro, and the mould growth model, WUFI® VTT. This study identified significant risks for this typical external wall system when constructed in a temperate climate.
Application and Development Countermeasures of CCUS Technology in China’s Petroleum Industry
Authors: Che Xingxiang , Yi Xiangyi , Dai Zhaohui , Zhang Ziwei , Zhang Yun
Published: October 2022

Greenhouse gas emissions cause many global problems. Under the strong promotion of the government’s two-carbon goals policy, China’s petroleum industry is actively carrying out the application of carbon capture, utilization, and storage (CCUS). The energy consumption and carbon emissions in China are reviewed, and the importance of the petroleum industry in the process of carbon emission reduction is clarified. The applications, advantages, and disadvantages of carbon capture, carbon utilization, and carbon sequestration technologies in China’s petroleum industry are summarized, respectively. The current challenges and risks faced by China’s petroleum industry in the operation of CCUS projects are analyzed, and corresponding suggestions are provided. This article aims to systematically provide references and help for the application of CCUS in China’s petroleum industry.
A Novel Stochastic Mixed-Integer-Linear-Logical Programming Model for Optimal Coordination of Hybrid Storage Systems in Isolated Microgrids Considering Demand Response
Authors: Tostado-Véliz Marcos , Ghadimi Ali Asghar , Miveh Mohammad Reza , Sánchez-Lozano Daniel , Escamez Antonio , Jurado Francisco
Published: October 2022

Storage systems and demand-response programs will play a vital role in future energy systems. Batteries, hydrogen or pumped hydro storage systems can be combined to form hybrid storage facilities to not only manage the intermittent behavior of renewable sources, but also to store surplus renewable energy in a practice known as ‘green’ storage. On the other hand, demand-response programs are devoted to encouraging a more active participation of consumers by pursuing a more efficient operation of the system. In this context, proper scheduling tools able to coordinate different storage systems and demand-response programs are essential. This paper presents a stochastic mixed-integer-lineal-logical framework for optimal scheduling of isolated microgrids. In contrast to other works, the present model includes a logical-based formulation to explicitly coordinate batteries and pumped hydro storage units. A case study on a benchmark isolated microgrid serves to validate the developed optimization model and analyze the effect of applying demand-response premises in microgrid operation. The results demonstrate the usefulness of the developed method, and it is found that operation cost and fuel consumption can be reduced by ~38% and ~82% by applying demand-response initiatives.
Exploring Extended Realities in Environmental Artistic Expression through Interactive Video Projections
Authors: Bongers Bert
Published: October 2022

The paper discusses the role of artistic expression and practices in extending realities. It presents a reflection and framework for VR/AR/MxR, Virtual Reality to Augmented or Mixed, or Extended Realities, as a continuum from completely virtual to mixed to completely real. It also reflects on the role of contemporary art practices and their role in extending or augmenting realities, from figurative to abstract, street art, to the scale of landscape art. Furthermore, the paper discusses the notion of live performance in art, which is common in music, contrasting a real-time ‘improvisation’ practice and composition practices, again a continuum as several mixed modes do exist. An effective technique for extending realities is video projection. This is discussed with examples from artistic expressions in various forms, and illustrated with some examples from the author’s practice in interactive audiovisual installations, and real time mobile projection performances and activities.
Optimization of the Fermentative Production of Rhizomucor miehei Lipase in Aspergillus oryzae by Controlling Morphology
Authors: Li Chao , Xu Dou , Xiong Zhiyue , Yang Yiming , Tian Guiwei , Wu Xuezhi , Wang Yonghong , Zhuang Yingping , Chu Ju , Tian Xiwei
Published: October 2022

Morphology plays an important role in the fermentation bioprocess of filamentous fungi. In this study, we investigated the controlling strategies of morphology that improved the efficiency of Rhizomucor miehei lipase (RML) production using a high-yield Aspergillus oryzae. First, the inoculated spore concentrations were optimized in seed culture, and the RML activity increased by 43.4% with the well-controlled mycelium pellets in both ideal sizes and concentrations. Then, the initial nitrogen source and agitation strategies were optimized to regulate the morphology of Aspergillus oryzae in a 5 L bioreactor, and the established stable fermentation system increased the RML activity to 232.0 U/mL, combined with an increase in total RML activity from 98,080 U to 487,179 U. Furthermore, the optimized fermentation strategy was verified by a high-yield Aspergillus oryzae and achieved an additional improvement of RML activity, up to 320.0 U/mL. Moreover, this optimized fermentation bioprocess was successfully scaled up to a 50 L bioreactor, and the RML activity reached 550.0 U/mL. This work has established a stable precision fermentation bioprocess for RML production by A. oryzae in bioreactors, and the controlling strategy developed in this study could potentially be extended to an industrial scale for RML production with high efficiency.
Bending Study of Six Biological Models for Design of High Strength and Tough Structures
Authors: Chen Guangming , Lin Tao , Guo Ce , Richter Lutz , Dai Ning
Published: October 2022

High strength and tough structures are beneficial to increasing engineering components service span. Nonetheless, improving structure strength and, simultaneously, toughness is difficult, since these two properties are generally mutually exclusive. Biological organisms exhibit both excellent strength and toughness. Using bionic structures from these biological organisms can be solutions for improving these properties of engineering components. To effectively apply biological models to design biomimetic structures, this paper analyses strengthening and toughening mechanisms of six fundamentally biological models obtained from biological organisms. Numerical models of three-point bending test are established to predict crack propagation behaviors of the six biological models. Furthermore, the strength and toughness of six biomimetic composites are experimentally evaluated. It is identified that the helical model possesses the highest toughness and satisfying strength. This work provides more detailed evidence for engineers to designate bionic models to the design of biomimetic composites with high strength and toughness.
Construction of Aptamer-Based Nanobiosensor for Breast Cancer Biomarkers Detection Utilizing g-C3N4/Magnetic Nano-Structure
Authors: Pourmadadi Mehrab , Yazdian Fatemeh , Ghorbanian Sohrabali , Shamsabadipour Amin , Khandel Elham , Rashedi Hamid , Rahdar Abbas , Díez-Pascual Ana M.
Published: October 2022

An electrochemical aptasensor has been developed to determine breast cancer biomarkers (CA 15-3). Aptamer chains were immobilized on the surface of the electrode by g-C3N4/Fe3O4 nanoparticles, which increased the conductivity and active surface area of the electrode. X-ray diffraction analysis (XRD), Fourier-transformed infrared spectroscopy (FTIR), and transmission electron microscopy (TEM) measurements have been carried out to characterize the nanomaterials. Cyclic voltammetry, square wave voltammetry, and electrochemical impedance spectroscopy have been used to characterize the developed electrode. The results demonstrate that the modified electrode has better selectivity for CA 15-3 compared to other biological molecules. It has a good electrochemical response to CA 15-3 with a detection limit of 0.2 UmL−1 and a linear response between 1 and 9 UmL−1. It has been used as a label-free sensor in potassium ferrocyanide medium and as methylene blue-labeled in phosphate buffer medium. This electrode was successfully applied to analyze the serum of diseased and healthy individuals, which corroborates its high potential for biosensing applications, especially for the diagnosis of breast cancer.
Real-Time Monitoring for Monolithic Movement of a Heritage Curtilage Using Wireless Sensor Networks
Authors: Shen Lulu , Yang Bo , Yang Yingwu , Yang Xuelin , Zhu Wenwei , Wang Qingzhong
Published: October 2022

Since monolithic movement is considered a promising technology to relocate historical buildings, corresponding real-time monitoring is of great interest due to the buildings’ age and poor structural integrity. However, the related paperwork and practical applications are still limited. This paper describes a wireless sensor network (WSN)-based strategy as a non-invasive approach to monitor heritage curtilage during monolithic movement. The collected data show that the inclination of the curtilage is almost negligible. With the aid of finite element simulation, it was found that the crack displacement curves changed from −0.02 to 0.07 mm, which is affected by moving direction while the value is not enough to cause structural cracks. The deformation of the steel underpinning beam, which is used to reinforce masonry walls and wooden pillars, is obviously related to the stiffness in different directions. Additionally, the strain variations of the steel chassis, which bear the vertical loads from wooden pillars and masonry walls, are less than 0.04%. This indicates that they are kept within the elastic range during monolithic movement. This work has proved that the WSN-based approach has the potential to be applied as an effective route in real-time monitoring of the monolithic movement of an historic building.
Analysis of Primary Cilium Expression and Hedgehog Pathway Activation in Mesothelioma Throws Back Its Complex Biology
Authors: Barbarino Marcella , Bottaro Maria , Spagnoletti Laura , de Santi Maria Margherita , Guazzo Raffaella , Defraia Chiara , Custoza Cosimo , Serio Gabriella , Iannelli Francesco , Pesetti Matilde , Aiello Raffaele , Rosati Diletta , Zanfrini Edoardo , Luzzi Luca , Bellan Cristiana , Giordano Antonio
Published: October 2022

The primary cilium (PC) is a sensory organelle present on the cell surface, modulating the activity of many pathways. Dysfunctions in the PC lead to different pathologic conditions including cancer. Hedgehog signaling (Hh) is regulated by PC and the loss of its control has been observed in many cancers, including mesothelioma. Malignant pleural mesothelioma (MPM) is a fatal cancer of the pleural membranes with poor therapeutic options. Recently, overexpression of the Hh transcriptional activator GL1 has been demonstrated to be associated with poor overall survival (OS) in MPM. However, unlike other cancers, the response to G-protein-coupled receptor smoothened (SMO)/Hh inhibitors is poor, mainly attributable to the lack of markers for patient stratification. For all these reasons, and in particular for the role of PC in the regulation of Hh, we investigated for the first time the status of PC in MPM tissues, demonstrating intra- and inter-heterogeneity in its expression. We also correlated the presence of PC with the activation of the Hh pathway, providing uncovered evidence of a PC-independent regulation of the Hh signaling in MPM. Our study contributes to the understanding MPM heterogeneity, thus helping to identify patients who might benefit from Hh inhibitors.
Respiratory Tract Cancer Incidences across Industry Groups: A Nationwide Cohort Study with More Than 70 Million Person-Years of Follow-Up
Authors: Baek Seong-Uk , Lee Woo-Ri , Yoo Ki-Bong , Choi Jun-Hyeok , Lee Kyung-Eun , Lee Wanhyung , Yoon Jin-Ha
Published: October 2022

The number of cases and incidence rates of laryngeal and lung cancers have been increasing globally. Therefore, identifying the occupational causes of such cancers is an important concern for policymakers to prevent cancers and deaths. We used national health insurance service claims data in Korea. We included 10,786,000 workers aged between 25 and 64 years. In total, 74,366,928 total person-years of follow-up were included in this study with a mean follow-up of 6.89 years for each person. The standardized incidence ratio (SIR) and 95% confidence intervals (CIs) referenced with the total workers were estimated. For laryngeal cancer, increased SIRs were observed in the land transportation industry among male workers (SIR [95% CI]: 1.65 [1.02–2.53]). For lung cancer, elevated SIRs were observed in the industries including animal production (1.72 [1.03–2.68]), fishing (1.70 [1.05–2.60]), mining (1.69 [1.22–2.27]), travel (1.41 [1.00–1.93]), and transportation (1.22 [1.15–1.30]) among male workers. For female works, healthcare (2.08 [1.04–3.72]) and wholesale (1.88 [1.18–2.85]) industries were associated with a high risk of lung cancer. As an increased risk of respiratory tract cancers has been identified in employees associated with certain industries, appropriate policy intervention is needed to prevent occupational cancers.
Next-Generation Antisense Oligonucleotide of TGF-β2 Enhances T Cell-Mediated Anticancer Efficacy of Anti-PD-1 Therapy in a Humanized Mouse Model of Immune-Excluded Melanoma
Authors: Lee Hong Kyu , Kim Cho-Won , Ahn Dohee , Go Ryeo-Eun , Choi Youngdong , Choi Kyung-Chul
Published: October 2022

Anti-programmed death-1 (PD-1) immunotherapy is one of the most promising therapeutic interventions for treating various tumors, including lung cancer, bladder cancer, and melanoma. However, only a subset of patients responds to anti-PD-1 therapy due to complicated immune regulation in tumors and the evolution of resistance. In the current study, we investigate the potential of a novel transforming growth factor-beta2 (TGF-β2) antisense oligonucleotide (ngTASO), as a combination therapy with an anti-PD-1 antibody in melanoma. This study was conducted in a melanoma-bearing human immune system mouse model that recapitulates immune-excluded phenotypes. We observed that the TGF-β2 blockade by ngTASO in combination with PD-1 inhibition downregulated the tumor intrinsic β-catenin, facilitated the infiltration of CD8+ cytotoxic lymphocytes (CTLs) in the tumor, and finally, enhanced the antitumor immune potentials and tumor growth delays. Blockade of TGF-β2 combined with PD-1 inhibition also resulted in downregulating the ratio of regulatory T cells to CTLs in the peripheral blood and tumor, resulting in increased granzyme B expression. In addition, co-treatment of ngTASO and anti-PD-1 augmented the PD-L1 expression in tumors, which is associated with an improved response to anti-PD-1 immunotherapy. These results indicate that the combination of ngTASO and anti-PD-1 exerts an enhanced T cell-mediated antitumor immune potential. Hence, co-inhibition of TGF-β2 and PD-1 is a potentially promising immunotherapeutic strategy for immune-excluded melanoma.
Securing Resection Margin Using Indocyanine Green Diffusion Range on Gastric Wall during NIR Fluorescence-Guided Surgery in Early Gastric Cancer Patients
Authors: Cho Minah , Kim Ki-Yoon , Park Sung Hyun , Kim Yoo Min , Kim Hyoung-Il , Hyung Woo Jin
Published: October 2022

Near-infrared (NIR) fluorescence lymphography-guided minimally invasive gastrectomy using indocyanine green (ICG) is employed to visualize draining lymphatic vessels and lymph nodes. Endoscopically injected ICG spreads along the gastric wall and emits fluorescence from the serosal surface of the stomach. We aimed to assess the efficacy of ICG diffusion in securing the resection margin. We retrospectively analyzed 503 patients with early gastric cancer located in the body of the stomach who underwent fluorescence lymphography-guided gastrectomy from 2018 to 2021. One day before surgery, ICG was endoscopically injected into four points of the submucosal layer peritumorally. We measured the extent of resection and the resection line based on the ICG diffusion area from the specimen using NIR imaging. The mean area of the ICG diffusion was 82.7 × 75.3 and 86.7 × 80.2 mm2 on the mucosal and serosal sides, respectively. After subtotal gastrectomy, the length of the proximal resection margin was 38.1 ± 20.1, 33.4 ± 22.2, and 28.7 ± 17.2 mm in gastroduodenostomy, loop gastrojejunostomy, and Roux-en-Y gastrojejunostomy, respectively. The ICG diffusion area along the gastric wall secured a resection margin of >28 mm. The ICG diffusion range can be used as a simple and easy method for determining the resection margin during gastrectomy using NIR imaging.
ZFP14 Regulates Cancer Cell Growth and Migration by Modulating p53 Protein Stability as Part of the MDM2 E3 Ubiquitin Ligase Complex
Authors: Mohibi Shakur , Chen Xinbin , Zhang Jin
Published: October 2022

Multi-zinc finger proteins that contain a KRAB domain are part of the biggest family of transcription factors in mammals. However, the physiological or pathological functions for the majority of them are unknown. Here, we showed that ZFP14 (also known as ZNF531) is a p53 target gene that can be induced upon genotoxic stress in a p53-dependent manner. To determine the function of ZFP14 in mouse and human cancer cell lines, we generated multiple cell lines where ZFP14 was knocked out. We showed that ZFP14-KO inhibits cancer cell growth and migration. We also showed that, as a target of p53, ZFP14, in turn, represses p53 expression and that the knockdown of p53 restores the potential of ZFP14-KO cells to proliferate and migrate. Mechanistically, we found that ZFP14 modulates p53 protein stability by increasing its ubiquitination via associating with and possibly enhancing MDM2/p53 complex integrity through its zinc finger domains. Our findings suggest that the reciprocal regulation of p53 and ZFP14 represents a novel p53-ZFP14 regulatory loop and that ZFP14 plays a role in p53-dependent tumor suppression.
Individualized Decision Making in Transperineal Prostate Biopsy: Should All Men Undergo an Additional Systematic Biopsy?
Authors: Sigle August , Suarez-Ibarrola Rodrigo , Benndorf Matthias , Weishaar Moritz , Morlock Jonathan , Miernik Arkadiusz , Gratzke Christian , Jilg Cordula A. , Grabbert Markus
Published: October 2022

Background: In prostate cancer (PC) diagnosis, additional systematic biopsy (SB) is recommended to complement MRI-targeted biopsy (TB) to address the limited sensitivity of TB alone. The combination of TB+SB is beneficial for diagnosing additional significant PC (sPC) but harmful in terms of the additional diagnosis of indolent PC (iPC), morbidity, and resource expenditures. We aimed to investigate the benefit of additional SB and to identify predictors for this outcome. Methods: We analyzed the frequency of upgrading to sPC by additional SB in a retrospective single-center cohort of 1043 men. Regression analysis (RA) was performed to identify predictors for this outcome. Reclassification rates of ISUP grade groups between prostate biopsy and a subsequent radical prostatectomy were assessed. Results: Additional SB led to upgrading to sPC in 98/1043 men (9.4%) and to the additional diagnosis of iPC in 71/1043 (6.8%). In RA, men harboring a PI-RADS 2-4 lesion were more likely to have TB results upgraded by SB (p < 0.01) compared to PI-RADS 5 men. When analyzing reclassification rates, additional SB reduced the upgrading to sPC from 43/214 (20.1%) to 8/214 (3.7%). In the PI-RADS 5 subgroup, this difference decreased: 4/87 (4.7%) with TB only vs. 1/87 (1.2%) with TB+SB. Conclusion: Men with a PI-RADS 5 lesion may obviate additional SB.
The RSL3 Induction of KLK Lung Adenocarcinoma Cell Ferroptosis by Inhibition of USP11 Activity and the NRF2-GSH Axis
Authors: Zhang Wenlong , Li Xiaohe , Xu Jiaqian , Wang Ying , Xing Zhengcao , Hu Shuming , Fan Qiuju , Lu Shaoyong , Cheng Jinke , Gu Jianmin , Cai Rong
Published: October 2022

Antioxidant transcription factor NRF2 plays a pivotal role in cell ferroptosis. KLK lung adenocarcinoma (LUAD) is a specific molecular subtype of Kras-mutant LUAD. The activation of mutant Kras in combination with the inactivation of Lkb1 and Keap1 abnormally increases NRF2 expression, while high NRF2 confers KLK LUAD cell resistance to ferroptosis. This study assessed the inhibition of NRF2-GSH axis to sensitize a small molecule RSL3 to induce KLK LUAD cell ferroptosis and then explored the underlying molecular mechanisms. The data showed that the NRF2-GSH inhibition sensitized RSL3 induction of KLK LUAD cell ferroptosis in vitro, while RSL3 treatment reduced level of NRF2 protein in KLK LUAD during ferroptosis. Moreover, RSL3 treatment inhibited activity of the NRF2-GSH signaling during in KLK LUAD cell ferroptosis in vitro and in vivo. Mechanistically, the RSL3 reduction of NRF2 expression was through the promotion of NRF2 ubiquitination in KLK LUAD cells. In addition, RSL3 was able to directly bind to USP11, a recently identified de-ubiquitinase of NRF2, and inactivate USP11 protein to induce NRF2 protein ubiquitination and degradation in KLK LUAD cells. These data revealed a novel mechanism of RSL3 induction in KLK LUAD cell ferroptosis by suppression of the USP11-NRF2-GSH signaling. Future study will confirm RSL3 as a novel therapeutic approach in control of KLK lung adenocarcinoma.
Carbon Ion Irradiation Downregulates Notch Signaling in Glioma Cell Lines, Impacting Cell Migration and Spheroid Formation
Authors: Kumar Vivek , Vashishta Mohit , Kong Lin , Lu Jiade J. , Wu Xiaodong , Dwarakanath Bilikere S. , Guha Chandan
Published: October 2022

Photon-based radiotherapy upregulates Notch signaling in cancer, leading to the acquisition of the stem cell phenotype and induction of invasion/migration, which contributes to the development of resistance to therapy. However, the effect of carbon ion radiotherapy (CIRT) on Notch signaling in glioma and its impact on stemness and migration is not explored yet. Human glioma cell lines (LN229 and U251), stable Notch1 intracellular domain (N1ICD) overexpressing phenotype of LN229 cells, and Notch inhibitor resistant LN229 cells (LN229R) were irradiated with either photon (X-rays) or (carbon ion irradiation) CII, and expressions of Notch signaling components were accessed by RT-PCR, Western blotting, and enzymatic assays and flow cytometry. Spheroid forming ability, cell migration, and clonogenic assay were used to evaluate the effect of modulated Notch signaling by irradiation. Our results show that X-ray irradiation induced the expression of Notch signaling components such as Notch receptors, target genes, and ADAM17 activity, while CII reduced it in glioma cell lines. The differential modulation of ADAM17 activity by CII and X-rays affected the cell surface levels of NOTCH1 and NOTCH2 receptors, as they were reduced by X-ray irradiation but increased in response to CII. Functionally, CII reduced the spheroid formation and migration of glioma cells, possibly by downregulating the N1ICD, as stable overexpression of N1ICD rescued these inhibitory effects of CII. Moreover, LN229R that are less reliant on Notch signaling for their survival showed less response to CII. Therefore, downregulation of Notch signaling resulting in the suppression of stemness and impaired cell migration by CII seen here may reduce tumor regrowth and disease dissemination, in addition to the well-established cytotoxic effects.
Multifaceted Roles of Retromer in EGFR Trafficking and Signaling Activation
Authors: Yang Zhe , Feng Zhengyang , Li Zebin , Teasdale Rohan D.
Published: October 2022

Mammalian retromer complex contributes to multiple early endosome-associated trafficking pathways whose origins are dependent on which sorting nexin (SNX) they are complexed with. In an attempt to dissect out the contribution of individual retromer–SNX complexes, we examined the trafficking of EGFR in detail within a series of KO cell line models. We demonstrated that the depletion of retromer subunit Vps35 leads to decreased EGFR protein levels in resting cells with enhanced association of EGFR with lysosomal compartments. Compared to control cells, the addition of EGF to Vps35 KO cells resulted in a reduced rate of EGFR degradation; AKT activation and cell prolferation rates were elevated, while ERK activation remained relatively unchanged. These observations are consistent with a prolonged temporal association of EGFR within early endosomes due to the inefficiency of early endosome-associated protein trafficking pathways or organelle maturation due to retromer absence. We did not fully delineate the discrete contributions from retromer-associated SNXs to the phenotypes observed from retromer Vps35 depletion. While each of the knock-outs of SNX1/2, SNX3, or SNX27 promotes the enhanced association of EGFR with early endosomal compartments, only the decreased EGF-mediated EGFR degradation was observed in SNX1/2 dKO cells, while the enhanced AKT activation was only increased in SNX3 KO or SNX27 KO cells. Despite this, each of the knock-outs showed increased EGF-stimulated cell proliferation rates.
Biophysical Determinants and Constraints on Sperm Swimming Velocity
Authors: Soulsbury Carl D. , Humphries Stuart
Published: October 2022

Over the last 50 years, sperm competition has become increasingly recognised as a potent evolutionary force shaping male ejaculate traits. One such trait is sperm swimming speed, with faster sperm associated with increased fertilisation success in some species. Consequently, sperm are often thought to have evolved to be longer in order to facilitate faster movement. However, despite the intrinsic appeal of this argument, sperm operate in a different biophysical environment than we are used to, and instead increasing length may not necessarily be associated with higher velocity. Here, we test four predictive models (ConstantPower Density, Constant Speed, Constant Power Transfer, Constant Force) of the relationship between sperm length and speed. We collated published data on sperm morphology and velocity from 141 animal species, tested for structural clustering of sperm morphology and then compared the model predictions across all morphologically similar sperm clusters. Within four of five morphological clusters of sperm, we did not find a significant positive relationship between total sperm length and velocity. Instead, in four morphological sperm clusters we found evidence for the Constant Speed model, which predicts that power output is determined by the flagellum and so is proportional to flagellum length. Our results show the relationship between sperm morphology (size, width) and swimming speed is complex and that traditional models do not capture the biophysical interactions involved. Future work therefore needs to incorporate not only a better understanding of how sperm operate in the microfluid environment, but also the importance of fertilising environment, i.e., internal and external fertilisers. The microenvironment in which sperm operate is of critical importance in shaping the relationship between sperm length and form and sperm swimming speed.
Mesenchymal Stem Cell-Derived Extracellular Vesicles for Therapeutic Use and in Bioengineering Applications
Authors: McLaughlin Caroline , Datta Pallab , Singh Yogendra P. , Lo Alexis , Horchler Summer , Elcheva Irina A. , Ozbolat Ibrahim T. , Ravnic Dino J. , Koduru Srinivas V.
Published: October 2022

Extracellular vesicles (EVs) are small lipid bilayer-delimited particles that are naturally released from cells into body fluids, and therefore can travel and convey regulatory functions in the distal parts of the body. EVs can transmit paracrine signaling by carrying over cytokines, chemokines, growth factors, interleukins (ILs), transcription factors, and nucleic acids such as DNA, mRNAs, microRNAs, piRNAs, lncRNAs, sn/snoRNAs, mtRNAs and circRNAs; these EVs travel to predecided destinations to perform their functions. While mesenchymal stem cells (MSCs) have been shown to improve healing and facilitate treatments of various diseases, the allogenic use of these cells is often accompanied by serious adverse effects after transplantation. MSC-produced EVs are less immunogenic and can serve as an alternative to cellular therapies by transmitting signaling or delivering biomaterials to diseased areas of the body. This review article is focused on understanding the properties of EVs derived from different types of MSCs and MSC–EV-based therapeutic options. The potential of modern technologies such as 3D bioprinting to advance EV-based therapies is also discussed.
Cell-Free Double-Stranded DNA to DNase Ratio Predicts Outcome after Primary Survived Cardiac Arrest
Authors: Rezar Richard , Lichtenauer Michael , Paar Vera , Aszlan Adrienne , Hofbauer Thomas M. , Kaufmann Reinhard , Wernly Sarah , Seelmaier Clemens , Mirna Moritz , Mangold Andreas , Lang Irene M. , Hoppe Uta C. , Ondracek Anna S. , Wernly Bernhard
Published: October 2022

(1) Double-stranded DNA (dsDNA) and deoxyribonuclease (DNase) as surrogate parameters for accumulating inflammatory hazards are insufficiently studied in resuscitation research. (2) Blood samples of 76 individuals after CA were analyzed 24 and 96 h after ICU admission. Plasma levels of dsDNA, interleukin-8, and monocyte chemoattractant protein-1 and activity of DNase were assessed along with baseline characteristics, intensive care measures, and outcome data. DsDNA/DNase ratio was used as main prognostication parameter. After calculating an optimal empirical cut-off for outcome prediction (death or Cerebral Performance Category ≥3 at 6 months), multivariable logistic regression was applied. (3) Using receiver operating characteristic (ROC) analysis, an area under the curve (AUC) of 0.65 (95% CI 0.50–0.79) was found for dsDNA/DNase after 24 h versus 0.83 (95% CI 0.73–0.92) after 96 h (p = 0.03). The empirical cut-off for dsDNA/DNase ratio after 96 h was 149.97 (Youden). DsDNA/DNase ratio was associated with unfavorable outcome at six months (aOR 1.006, 95% CI 1.0017–1.0094, p = 0.005). In multivariable analysis, the association of dsDNA/DNase ratio independently predicted outcome as a continuous variable (aOR 1.004, 95% CI 1.0004–1.0079, p = 0.029) after adjusting for potential confounders. (4) DsDNA/DNase ratio at 96 h demonstrates good predictive performance for estimating outcome after CA.
Hyaluronan Regulates Neuronal and Immune Function in the Rat Small Intestine and Colonic Microbiota after Ischemic/Reperfusion Injury
Authors: Bosi Annalisa , Banfi Davide , Bistoletti Michela , Catizzone Lucia Martina , Chiaravalli Anna Maria , Moretto Paola , Moro Elisabetta , Karousou Evgenia , Viola Manuela , Giron Maria Cecilia , Crema Francesca , Rossetti Carlo , Binelli Giorgio , Passi Alberto , Vigetti Davide , Giaroni Cristina , Baj Andreina
Published: October 2022

Background: Intestinal ischemia and reperfusion (IRI) injury induces acute and long-lasting damage to the neuromuscular compartment and dysmotility. This study aims to evaluate the pathogenetic role of hyaluronan (HA), a glycosaminoglycan component of the extracellular matrix, as a modulator of the enteric neuronal and immune function and of the colonic microbiota during in vivo IRI in the rat small intestine. Methods: mesenteric ischemia was induced in anesthetized adult male rats for 60 min, followed by 24 h reperfusion. Injured, sham-operated and non-injured animals were treated with the HA synthesis inhibitor, 4-methylumbelliferone (4-MU 25 mg/kg). Fecal microbiota composition was evaluated by Next Generation Sequencing. Neutrophil infiltration, HA homeostasis and toll like receptor (TLR2 and TLR4) expression in the small intestine were evaluated by immunohistochemical and biomolecular approaches (qRT-PCR and Western blotting). Neuromuscular responses were studied in vitro, in the absence and presence of the selective TLR2/4 inhibitor, Sparstolonin B (SsnB 10, 30 µM). Results: 4-MU significantly reduced IRI-induced enhancement of potentially harmful Escherichia and Enterococcus bacteria. After IRI, HA levels, neutrophil infiltration, and TLR2 and TLR4 expression were significantly enhanced in the muscularis propria, and were significantly reduced to baseline levels by 4-MU. In the injured, but not in the non-injured and sham-operated groups, SsnB reduced both electrical field-stimulated (EFS, 0.1–40 Hz) contractions and EFS-induced (10 Hz) non-cholinergic non-adrenergic relaxations. Conclusions: enhanced HA levels after intestinal IRI favors harmful bacteria overgrowth, increases neutrophil infiltration and promotes the upregulation of bacterial target receptors, TLR2 and TLR4, in the muscularis propria, inducing a pro-inflammatory state. TLR2 and TLR4 activation may, however, underlay a provisional benefit on excitatory and inhibitory neuronal pathways underlying peristalsis.