bluuebunny/crossref_metadata_2025 huggingface dataset:
Synchrotron-Based X-ray Photoelectron Microscopy of LMO/LAGP/Cu Thin-Film Solid-State Lithium Metal Batteries
Authors: Kazemian Majid , Amati Matteo , Gregoratti Luca , Kiskinova Maya , Bozzini Benedetto
Published: October 2023

Solid-state batteries (SSB), characterized by solid-state electrolytes—in particular inorganic ones (ISSE)—are an ideal option for the safe implementation of metallic Li anodes. Even though SSBs with ISSEs have been extensively investigated over the last two decades, they still exhibit a series of technological drawbacks. In fact, mechano-chemical issues, mainly the stability of the electrolyte/anode interface, hinder their widespread application. The present investigation focusses on a thin-film LMO (Lithium-Manganese-Oxide)/LAGP (LiAlGe Phosphate)/Copper, anodeless Lithium-metal battery and explores the morphochemical evolution of the electrode/electrolyte interfaces with synchrotron-based Scanning Photoelectron Microscopy (SPEM) of intact pristine and cycled cells. Chemical images were acquired with submicrometer resolution, to highlight the coupled geometrical and chemical-state changes caused by electrochemical ageing. Geometrical changes of the electrolyte/cathode interface were induced by periodic volume changes, causing de-cohesion of the solid-solid contact, but no chemical-state changes accompany the cathodic damaging mode. Instead, shape changes of the electrolyte/anode region pinpoint the correlation between mechanical damaging with the decomposition of the LAGP ISSE, due to the reduction of Ge, triggered by the contact with elemental Li. The micro-spectroscopic approach adopted in this study enabled the assessment of the highly localized nature of the cathodic and anodic degradation modes in SSB devices and to single out the chemical and mechanical contributions.
Influence of Blood Rheology and Turbulence Models in the Numerical Simulation of Aneurysms
Authors: Brambila-Solórzano Alberto , Méndez-Lavielle Federico , Naude Jorge Luis , Martínez-Sánchez Gregorio Josué , García-Rebolledo Azael , Hernández Benjamín , Escobar-del Pozo Carlos
Published: October 2023

An aneurysm is a vascular malformation that can be classified according to its location (cerebral, aortic) or shape (saccular, fusiform, and mycotic). Recently, the study of blood flow interaction with aneurysms has gained attention from physicians and engineers. Shear stresses, oscillatory shear index (OSI), gradient oscillatory number (GON), and residence time have been used as variables to describe the hemodynamics as well as the origin and evolution of aneurysms. However, the causes and hemodynamic conditions that promote their growth are still under debate. The present work presents numerical simulations of three types of aneurysms: two aortic and one cerebral. Simulation results showed that the blood rheology is not relevant for aortic aneurysms. However, for the cerebral aneurysm case, blood rheology could play a relevant role in the hemodynamics. The evaluated turbulence models showed equivalent results in both cases. Lastly, a simulation considering the fluid–structure interaction (FSI) showed that this phenomenon is the dominant factor for aneurysm simulation.
MicroRNAs Signature Panel Identifies Heavy Drinkers with Alcohol-Associated Cirrhosis from Heavy Drinkers without Liver Injury
Authors: Shihana Fathima , Joglekar Mugdha V. , Schwantes-An Tae-Hwi , Hardikar Anandwardhan A. , Seth Devanshi
Published: October 2023

Background: Alcohol-associated liver disease (ALD) is the most common disorder of prolonged drinking. Mechanisms underlying cirrhosis in such patients remain unclear. MicroRNAs play regulatory role in several diseases, are affected by alcohol and may be important players in alcohol use disorders, such as cirrhosis. Methods: We investigated serum samples from heavy chronic alcohol users (80 g/day (male) and 50 g/day (female) for ≥10 years) that were available from our previously reported GenomALC study. A subset of GenomALC drinkers with liver cirrhosis (cases, n = 24) and those without significant liver disease (drinking controls, n = 23) were included. Global microRNA profiling was performed using high-throughput real-time quantitative PCR to identify the microRNA signatures associated with cirrhosis. Ingenuity Pathway Analysis (IPA) software was utilized to identify target mRNAs of significantly altered microRNAs, and molecular pathways were analysed. Identified microRNAs were analysed for correlation with traditional liver disease biomarkers and risk gene variants previously reported from GenomALC genome-wide association study. Results: The expression of 21 microRNAs was significantly downregulated in cases compared to drinking controls (p < 0.05, ∆∆Ct > 1.5-fold). Seven microRNAs (miR-16, miR-19a, miR-27a, miR-29b, miR-101, miR-130a, and miR-191) had a highly significant correlation (p < 0.001) with INR, bilirubin and MELD score. Three microRNAs (miR-27a, miR-130a and miR-191) significantly predicted cases with AUC-ROC 0.8, 0.78 and 0.85, respectively (p < 0.020); however, INR performed best (0.97, p < 0.001). A different set of six microRNAs (miR-19a, miR-26a, miR-101, miR-151-3p, miR-221, and miR-301) showed positive correlation (ranging from 0.32 to 0.51, p < 0.05) with rs10433937:HSD17B13 gene variant, associated with the risk of cirrhosis. IPA analysis revealed mRNA targets of the significantly altered microRNAs associated with cell death/necrosis, fibrosis and increased steatosis, particularly triglyceride metabolism. Conclusions: MicroRNA signatures in drinkers distinguished those with liver cirrhosis from drinkers without liver disease. We identified mRNA targets in liver functions that were enriched for disease pathogenesis pathways.
Monooxygenases and Antibiotic Resistance: A Focus on Carbapenems
Authors: Minerdi Daniela , Loqui Davide , Sabbatini Paolo
Published: October 2023

Carbapenems are a group of broad-spectrum beta-lactam antibiotics that in many cases are the last effective defense against infections caused by multidrug-resistant bacteria, such as some strains of Klebsiella pneumoniae, Escherichia coli, Pseudomonas aeruginosa, and Acinetobacter baumannii. Resistance to carbapenems has emerged and is beginning to spread, becoming an ongoing public-health problem of global dimensions, causing serious outbreaks, and dramatically limiting treatment options. This paper reviews the role of flavin monooxygenases in antibiotic resistance, with a specific focus on carbapenem resistance and the recently discovered mechanism mediated by Baeyer–Villiger monooxygenases. Flavin monooxygenases are enzymes involved in the metabolism and detoxification of compounds, including antibiotics. Understanding their role in antibiotic resistance is crucial. Carbapenems are powerful antibiotics used to treat severe infections caused by multidrug-resistant bacteria. However, the rise of carbapenem-resistant strains poses a significant challenge. This paper explores the mechanisms by which flavin monooxygenases confer resistance to carbapenems, examining molecular pathways and genetic factors. Additionally, this paper highlights the discovery of Baeyer–Villiger monooxygenases’ involvement in antibiotic resistance. These enzymes catalyze the insertion of oxygen atoms into specific chemical bonds. Recent studies have revealed their unexpected role in promoting carbapenem resistance. Through a comprehensive analysis of the literature, this paper contributes to the understanding of the interplay between flavin monooxygenases, carbapenem resistance, and Baeyer–Villiger monooxygenases. By exploring these mechanisms, it aims to inform the development of strategies to combat antibiotic resistance, a critical global health concern.
The Hypothalamus of the Beaked Whales: The Paraventricular, Supraoptic, and Suprachiasmatic Nuclei
Authors: Sacchini Simona , Bombardi Cristiano , Arbelo Manuel , Herráez Pedro
Published: October 2023

The hypothalamus is the body’s control coordinating center. It is responsible for maintaining the body’s homeostasis by directly influencing the autonomic nervous system or managing hormones. Beaked whales are the longest divers among cetaceans and their brains are rarely available for study. Complete hypothalamic samples from a female Cuvier’s beaked whale and a male Blainville’s beaked whale were processed to investigate the paraventricular (PVN) and supraoptic (SON) nuclei, using immunohistochemical staining against vasopressin. The PVN occupied the preoptic region, where it reached its maximum size, and then regressed in the anterior or suprachiasmatic region. The SON was located from the preoptic to the tuberal hypothalamic region, encompassing the optical structures. It was composed of a retrochiasmatic region (SONr), which bordered and infiltrated the optic tracts, and a principal region (SONp), positioned more medially and dorsally. A third vasopressin-positive nucleus was also detected, i.e., the suprachiasmatic nucleus (SCN), which marked the end of the SON. This is the first description of the aforementioned nuclei in beaked whales—and in any marine mammals—as well as their rostro-caudal extent and immunoreactivity. Moreover, the SCN has been recognized for the first time in any marine mammal species.
IL-33/ST2 Axis: A Potential Therapeutic Target in Neurodegenerative Diseases
Authors: Jia Zexi , Guo Mengtian , Ge Xintong , Chen Fanglian , Lei Ping
Published: October 2023

Interleukin 33 (IL-33) belongs to the IL-1 family and is localized in the nucleus. IL-33 is primarily composed of three distinct domains, namely the N-terminal domain responsible for nuclear localization, the intermediate sense protease domain, and the C-terminal cytokine domain. Its specific receptor is the suppression of tumorigenicity 2 (ST2), which is detected in serum-stimulated fibroblasts and oncogenes. While most other cytokines are actively produced in cells, IL-33 is passively produced in response to tissue damage or cell necrosis, thereby suggesting its role as an alarm following cell infection, stress, or trauma. IL-33 plays a crucial role in congenital and acquired immunity, which assists in the response to environmental stress and maintains tissue homeostasis. IL-33/ST2 interaction further produces many pro-inflammatory cytokines. Moreover, IL-33 is crucial for central nervous system (CNS) homeostasis and the pathogenic mechanisms underlying CNS degenerative disorders. The present work summarizes the structure of IL-33, its fundamental activities, and its role in immunoregulation and neurodegenerative diseases. Therefore, this work proposes that IL-33 may play a role in the pathogenic mechanism of diseases and can be used in the development of treatment strategies.
Nicotinic Acid-Mediated Modulation of Metastasis-Associated Protein 1 Methylation and Inflammation in Brain Arteriovenous Malformation
Authors: Deng Xinpeng , Zhou Shengjun , Hu Ziliang , Gong Fanyong , Zhang Junjun , Zhou Chenhui , Lan Wenting , Gao Xiang , Huang Yi
Published: October 2023

We explored metastasis-associated protein 1 (MTA1) promoter methylation in the development of brain arteriovenous malformation (BAVM). The clinical data of 148 sex- and age-matched BAVMs and controls were collected, and the MTA1 DNA methylation in peripheral white blood cells (WBC) was assessed by bisulfite pyrosequencing. Among them, 18 pairs of case–control samples were used for WBC mRNA detection, 32 pairs were used for WBC MTA1 protein measurement, and 50 pairs were used for plasma inflammatory factor analysis. Lipopolysaccharide (LPS) treatment was used to induce an inflammatory injury cell model of human brain microvascular endothelial cells (BMECS). 5-Aza-2′-deoxycytidine (5-AZA), nicotinic acid (NA), and MTA1 siRNAs were used in functional experiments to examine BMECS behaviors. RT-qPCR, Western blot, and ELISA or cytometric bead arrays were used to measure the expression levels of MTA1, cytokines, and signaling pathway proteins in human blood or BMECS. The degree of MTA1 promoter methylation was reduced in BAVM compared with the control group and was inversely proportional to MTA1 expression. Plasma ApoA concentrations in BAVM patients were significantly lower than those in controls and correlated positively with MTA1 promoter methylation and negatively with MTA1 expression. The expression of cytokine was markedly higher in BAVM than in controls. Cell experiments showed that 5-AZA decreased the methylation level of MTA1 and increased the expression of MTA1 protein. LPS treatment significantly increased cytokine concentrations (p < 0.05). NA and MTA1 silencing could effectively reverse the LPS-mediated increase in IL-6 and TNF-α expression through the NF-κB pathway. Our study indicated that NA may regulate MTA1 expression by affecting promoter DNA methylation, improve vascular inflammation through the NF-κB pathway, and alleviate the pathological development of BAVM.
Sugar Extraction from Secondary Agricultural Waste Biomass Using Hydrothermal Carbonization and Direct Contact Membrane Distillation
Authors: Sagar Viral , Lynam Joan G. , Parrenin Amelia G.
Published: October 2023

Sustainable and renewable sources of liquid and solid fuels are essential to prevent fossil fuel use from damaging the environment. Secondary agricultural residues, which are already transported to food processing centers, have great potential to be converted into biofuels. The wastes from coffee roasting, sugar production, and rice milling have been investigated using hydrothermal carbonization (HTC) to produce aqueous products containing monosaccharides alongside solid biofuels. These sugar-laden liquid products were characterized after pretreating coffee silverskins, sugarcane bagasse, and rice husks with HTC. They were then concentrated using direct contact membrane distillation (DCMD), a low-energy process that can use waste heat from other biorefinery processes. The higher heating value of the solid products was also characterized by bomb calorimetry. The liquid products from HTC of these wastes from food production were found to contain varying concentrations of glucose, xylose, galactose, and arabinose. DCMD was capable of concentrating the liquid products up to three times their original concentrations. Little difference was found among the higher heating values of the solid products after 180 °C HTC pretreatment compared to 200 °C pretreatment. HTC of waste from food processing can provide solid biofuels and liquid products containing sugars that can be concentrated using DCMD.
Analysis of Membrane Type-1 Matrix Metalloproteinase (MT1-MMP, MMP14) in Eutopic and Ectopic Endometrium and in Serum and Endocervical Mucus of Endometriosis
Authors: Maoga Jane B. , Riaz Muhammad A. , Mwaura Agnes N. , Mecha Ezekiel , Omwandho Charles O. A. , Scheiner-Bobis Georgios , Meinhold-Heerlein Ivo , Konrad Lutz
Published: October 2023

Background: Membrane type-matrix metalloproteinases (MT-MMPs) are a subgroup of the matrix metalloproteinases (MMPs) family and are key molecules in the degradation of the extracellular matrix. Membrane type-1 matrix metalloproteinase (MT1-MMP, MMP14) is often deregulated in different cancer tissues and body fluids of human cancer patients; however, MT1-MMP levels in endometriosis and adenomyosis patients are currently unknown. Materials and Methods: Tissue samples from patients with and without endometriosis or adenomyosis were analyzed with immunohistochemistry for the localization of MT1-MMP. Serum and endocervical mucus samples from patients with and without endometriosis or adenomyosis were investigated with MT1-MMP ELISAs. Results: MT1-MMP was localized preferentially in the glands of eutopic and ectopic endometrium. MT1-MMP protein levels are significantly reduced in ovarian endometriosis (HSCORE = 31) versus eutopic endometrium (HSCORE = 91) and adenomyosis (HSCORE = 149), but significantly increased in adenomyosis (HSCORE = 149) compared to eutopic endometrium (HSCORE = 91). Similarly, analysis of the levels of MT1-MMP using enzyme-linked immune assays (ELISAs) demonstrated a significant increase in the concentrations of MT1-MMP in the serum of endometriosis patients (1.3 ± 0.8) versus controls (0.7 ± 0.2), but not in the endocervical mucus. Furthermore, MT1-MMP levels in the endocervical mucus of patients with endometriosis were notably reduced in patients using contraception (3.2 ± 0.4) versus those without contraception (3.8 ± 0.2). Conclusions: Taken together, our findings showed an opposite regulation of MT1-MMP in the tissue of ovarian endometriosis and adenomyosis compared to eutopic endometrium without endometriosis but increased serum levels in patients with endometriosis.
Effects of Tiliroside and Lisuride Co-Treatment on the PI3K/Akt Signal Pathway: Modulating Neuroinflammation and Apoptosis in Parkinson’s Disease
Authors: Alkholifi Faisal K. , Devi Sushma , Aldawsari Mohammed F. , Foudah Ahmed I. , Alqarni Mohammed H. , Salkini Mohamad Ayman , Sweilam Sherouk Hussein
Published: October 2023

Researchers are actively exploring potential bioactive compounds to enhance the effectiveness of Lisuride (Lis) in treating Parkinson’s disease (PD) over the long term, aiming to mitigate the serious side effects associated with its extended use. A recent study found that combining the dietary flavonoid Tiliroside (Til) with Lis has potential anti-Parkinson’s benefits. The study showed significant improvements in PD symptoms induced by 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) when Til and Lis were given together, based on various behavioral tests. This combined treatment significantly improved motor function and protected dopaminergic neurons in rats with PD induced by MPTP. It also activated important molecular pathways related to cell survival and apoptosis control, as indicated by the increased pAkt/Akt ratio. Til and Lis together increased B-cell lymphoma 2 (Bcl-2), decreased caspase 3 activity, and prevented brain cell decay. Co-administration also reduced tumor necrosis factor alpha (TNF-α) and Interleukin-1 (IL-1). Antioxidant markers such as superoxide dismutase (SOD), catalase, and reduced glutathione significantly improved compared to the MPTP-induced control group. This study shows that using Til and Lis together effectively treats MPTP-induced PD in rats, yielding results comparable to an 8 mg/kg dose of levodopa, highlighting their potential as promising Parkinson’s treatments.
Weighted Trajectory Analysis and Application to Clinical Outcome Assessment
Authors: Chauhan Utkarsh , Zhao Kaiqiong , Walker John , Mackey John R.
Published: October 2023

The Kaplan–Meier (KM) estimator is widely used in medical research to estimate the survival function from lifetime data. KM estimation is a powerful tool to evaluate clinical trials due to simple computational requirements, its use of a logrank hypothesis test, and the ability to censor patients. However, KM estimation has several constraints and fails to generalize to ordinal variables of clinical interest, such as toxicity and ECOG performance. We devised weighted trajectory analysis (WTA) to combine the advantages of KM estimation with the ability to visualize and compare treatment groups for ordinal variables and fluctuating outcomes. To assess statistical significance, we developed a new hypothesis test analogous to the logrank test. We demonstrated the functionality of WTA through 1000-fold clinical trial simulations of unique stochastic models of chemotherapy toxicity and schizophrenia disease course. With increments in sample size and hazard ratio, we compared the performance of WTA to KM estimation and the generalized estimating equation (GEE). WTA generally required half the sample size to achieve comparable power to KM estimation; advantages over the GEE included its robust nonparametric approach and summary plot. We also applied WTA to real clinical data: the toxicity outcomes of melanoma patients receiving immunotherapy and the disease progression of patients with metastatic breast cancer receiving ramucirumab. The application of WTA demonstrated that using traditional methods such as KM estimation can lead to both type I and II errors by failing to model illness trajectory. This article outlines a novel method for clinical outcome assessment that extends the advantages of Kaplan–Meier estimates to ordinal outcome variables.
Indentation and Detachment in Adhesive Contacts between Soft Elastomer and Rigid Indenter at Simultaneous Motion in Normal and Tangential Direction: Experiments and Simulations
Authors: Lyashenko Iakov A. , Popov Valentin L. , Borysiuk Vadym
Published: October 2023

In reported experiments, a steel indenter was pressed into a soft elastomer layer under varying inclination angles and subsequently was detached under various inclination angles too. The processes of indentation and detachment were recorded with a video camera, and the time dependences of the normal and tangential components of the contact force and the contact area, as well as the average contact pressure and average tangential stresses, were measured as functions of the inclination angle. Based on experimental results, a simple theoretical model of the indentation process is proposed, in which tangential and normal contacts are considered independently. Both experimental and theoretical results show that at small indentation angles (when the direction of motion is close to tangential), a mode with elastomer slippage relative to the indenter is observed, which leads to complex dynamic processes—the rearrangement of the contact boundary and the propagation of elastic waves (similar to Schallamach waves). If the angle is close to the normal angle, there is no slipping in the contact plane during the entire indentation (detachment) phase.
A Reinforcement Learning Approach to Robust Scheduling of Permutation Flow Shop
Authors: Zhou Tao , Luo Liang , Ji Shengchen , He Yuanxin
Published: October 2023

The permutation flow shop scheduling problem (PFSP) stands as a classic conundrum within the realm of combinatorial optimization, serving as a prevalent organizational structure in authentic production settings. Given that conventional scheduling approaches fall short of effectively addressing the intricate and ever-shifting production landscape of PFSP, this study proposes an end-to-end deep reinforcement learning methodology with the objective of minimizing the maximum completion time. To tackle PFSP, we initially model it as a Markov decision process, delineating pertinent states, actions, and reward functions. A notably innovative facet of our approach involves leveraging disjunctive graphs to represent PFSP state information. To glean the intrinsic topological data embedded within the disjunctive graph’s underpinning, we architect a policy network based on a graph isomorphism network, subsequently trained through proximal policy optimization. Our devised methodology is compared with six baseline methods on randomly generated instances and the Taillard benchmark, respectively. The experimental results unequivocally underscore the superiority of our proposed approach in terms of makespan and computation time. Notably, the makespan can save up to 183.2 h in randomly generated instances and 188.4 h in the Taillard benchmark. The calculation time can be reduced by up to 18.70 s for randomly generated instances and up to 18.16 s for the Taillard benchmark.
Towards Environment-Aware Fall Risk Assessment: Classifying Walking Surface Conditions Using IMU-Based Gait Data and Deep Learning
Authors: Yıldız Abdulnasır
Published: October 2023

Fall risk assessment (FRA) helps clinicians make decisions about the best preventative measures to lower the risk of falls by identifying the different risks that are specific to an individual. With the development of wearable technologies such as inertial measurement units (IMUs), several free-living FRA methods based on fall predictors derived from IMU-based data have been introduced. The performance of such methods could be improved by increasing awareness of the individuals’ walking environment. This study aims to introduce and analyze a 25-layer convolutional neural network model for classifying nine walking surface conditions using IMU-based gait data, providing a basis for environment-aware FRAs. A database containing data collected from thirty participants who wore six IMU sensors while walking on nine surface conditions was employed. A systematic analysis was conducted to determine the effects of gait signals (acceleration, magnetic field, and rate of turn), sensor placement, and signal segment size on the method’s performance. Accuracies of 0.935 and 0.969 were achieved using a single and dual sensor, respectively, reaching an accuracy of 0.971 in the best-case scenario with optimal settings. The findings and analysis can help to develop more reliable and interpretable fall predictors, eventually leading to environment-aware FRA methods.
The Surgical Odyssey: Romania’s Contributions to Pituitary Gland Procedures
Authors: Toader Corneliu , Popa Andrei-Adrian , Covache-Busuioc Razvan-Adrian , Bratu Bogdan-Gabriel , Ciurea Alexandru Vlad
Published: October 2023

The pituitary gland, a puzzling medical subject up until the 20th century, had its early pathologies first documented in the 19th century by Pierre Marie and Hutchinson, where the gland’s meaningful study was hindered by its hard-to-reach location. This paper revisits the pioneering work of Romanian doctors such as Gheorghe Marinescu, Nicolae Paulescu, and Grigore T. Popa in surgical techniques targeting the pituitary gland. Marinescu’s 1892 experiment, albeit unsuccessful, laid the groundwork for future research in this area. Before Paulescu, surgical attempts could be classified into three types: oral, cranial, and sphenopalatine fossa approaches—all of which were notably dangerous and often resulted in fatal bleeding. Paulescu was the first to successfully and safely perform a complete in vivo hypophysectomy, opting for an innovative subtemporal method. He also conducted extensive research over four years to identify the gland’s essential functions. Later, a 1938 study by Popa and Harris demonstrated a temporal approach to the hypothalamo-hypophysial region in a rabbit. These groundbreaking contributions significantly influenced the trajectory of pituitary gland surgery.
The Effects of Visual Complexity and Task Difficulty on the Comprehensive Cognitive Efficiency of Cluster Separation Tasks
Authors: Guo Qi , Chen Yan
Published: October 2023

Cluster separation is required to perform multi-class visual statistics tasks and plays an essential role in information processing in visualization. This cognition behavioral study investigated the cluster separation task and the effects of visual complexity and task difficulty. A total of 32 college students (18 men and 14 women, with ages ranging from 18 to 25 years; mean = 21.2, SD = 3.9) participated in this study. The observers’ average response accuracy, reaction time, mental effort, and comprehensive cognitive efficiency were measured as functions of three levels of visual complexity and task difficulty. The levels of visual complexity and task difficulty were quantified via an optimized complexity evaluation method and discrimination judgment task, respectively. The results showed that visual complexity and task difficulty significantly influenced comprehensive cognitive efficiency. Moreover, a strong interaction was observed between the effects of visual complexity and task difficulty. However, there was no positive linear relationship between the mental effort and the complexity level. Furthermore, two-dimensional color × shape redundant coding showed higher cognitive efficiency at low task difficulty levels. In contrast, the one-dimensional color encoding approach showed higher cognitive efficiency at increased task difficulty levels. The findings of this study provide valuable insights into designing more efficient and user-friendly visualization in the future.
The Influence of Victim Self-Disclosure on Bystander Intervention in Cyberbullying
Authors: Zeng Yuze , Xiao Junze , Li Danfeng , Sun Jiaxiu , Zhang Qingqi , Ma Ai , Qi Ke , Zuo Bin , Liu Xiaoqian
Published: October 2023

The frequent occurrences of cyberbullying on social platforms have sparked a great deal of social conflict, and bystander intervention plays a crucial role in preventing the escalation of cyberbullying. This research examines the impact of victim self-disclosure on bystander intervention in cyberbullying through two experimental studies. The studies collected data from March to July of 2022, utilizing a convenience sampling approach to recruit university students as experiment participants. Study 1 recruited 247 valid participants, while Study 2 recruited 522 eligible participants. The results of Study 1 indicate that the perceptible dimensions (frequency, privacy, and valence) of victim self-disclosure impact bystander intervention. Specifically, in a low privacy context, positive self-disclosure increases bystander intervention, while negative self-disclosure does the opposite. The results of Study 2 suggest that the valence of self-disclosure affects bystander intervention through the mediation of victim blaming, with interpersonal distance moderating the impact of victim self-disclosure valence on the extent of victim blaming. This moderated mediation model clarifies the psychological process by which the valence of victim self-disclosure affects bystander intervention. The findings of this study contribute to the understanding of the social psychological process behind bystander intervention, providing a scientific basis and pathway for reducing cyberbullying and fostering a harmonious online environment.
Energy-Based Design: Improving Modern Brazilian Buildings Performance through Their Shading Systems, the Nova Cintra Case Study
Authors: Mateus Daniel , Henriques Gonçalo Castro
Published: October 2023

Current research applies an energy-based design model to improve performance in existing modern buildings, in Rio de Janeiro, from the 1940’s, improving these buildings’ shading systems. This article proposes a methodology tested through a case study, the Nova Cintra building. The methodology starts by analysing the original shading system performance, regarding insolation, illuminance and air temperature. Using these results, proposes two computacional methods to improve performance: (1) a combinatorial modelling process, recombining the existing shading systems positions in the building’s north façade; and (2) a transformation process, using parametric and algorithmic–parametric modelling, to improve the existing shading systems performance. Both processes use optimization algorithms. The results of these modelling and optimization methods are compared with the results of the original system and suggests an improvement between 111.1% and 590.4% for insolation; between 360.9% and 84.4% for illuminance; and between 2.9% and 3.0% for air temperature, considering winter and summer solstices. This improvement aims at reducing the buildings’ energy consumption and foresees the production of renewable energy from solar harvesting, to mitigate climate change.
Graphene and Nanoclay as Processing Aid Agents: A Study on Rheological Behavior in Polystyrene
Authors: Genoyer Julie , Helal Emna , Gutierrez Giovanna , Moghimian Nima , David Eric , Demarquette Nicole R.
Published: October 2023

The effectiveness of layered particles as processing aid agents in molten polystyrene was studied. Three graphene grades and two clays of different lateral size were selected for this purpose. The morphologies of the composites were observed using scanning electron microscopy. Steady shear measurements were carried out and the Carreau–Yasuda model with yield stress was applied to the experimental results. A decrease in viscosity was observed at 2 wt.% of particle content for almost all composites. The most efficient particle for reducing viscosity was found to be graphene in a loose agglomerated configuration. Graphene and clay particles with similar dispersion states had a similar effect on the viscosity, inducing a decrease by 29% and 22%, respectively, suggesting comparable efficiency as processing aid agents. The observed decrease in viscosity is attributed to the phenomenon of superlubricity, which is a lubricating mechanism that is closely linked to the atomic structure of the particles.
The Excretion of Cisplatin after Hyperthermic Intrathoracic Chemotherapy
Authors: Larisch Christopher , Markowiak Till , Ried Michael , Nowak Dennis , Hofmann Hans-Stefan , Rakete Stefan
Published: October 2023

Hyperthermic intrathoracic chemotherapy (HITOC) is an additional intraoperative treatment option within the multimodality therapy of pleural malignancies. A chemotherapy perfusion with high-dose cisplatin is performed over a period of 60 min after surgical cytoreduction to improve local tumour control through the eradication of residual tumour cells. Although HITOC is increasingly used, there is only little scientific evidence about the necessary safety measures after HITOC. Therefore, the objective of this study was an analysis of cisplatin excretion via various body fluids after HITOC, with the aim of providing recommendations on occupational health and safety. Five patients undergoing HITOC were included. Before and after the HITOC, as well as during the following days, serum, urine, and bronchial secretion, as well as pleural effusion, were sampled. The platinum levels in the samples were measured using ICP-MS (inductively coupled plasma-mass spectrometry). Immediately after the HITOC, the mean levels of cisplatin increased dramatically in the serum (from 0.79 to 1349 µg/L), urine (from 3.48 to 10,528 µg/g creatinine), and bronchial secretion (from 0.11 to 156 µg/L). Thereafter, the cisplatin levels dropped to 133 µg/L in the serum and 994 µg/g creatinine in the urine within nine days after the HITOC. The AUC ratio shows 59% of the cisplatin being excreted via the urine after 48 h. The sampling of pleural effusion started 24 h after the HITOC, and the cisplatin levels decreased from 618 to 93 µg/L within nine days. Although the cisplatin levels in the body fluids of HITOC patients are much lower compared to patients receiving intravenous chemotherapy, a significant amount of cisplatin is excreted via these body fluids. Consequently, safety precautions must be implemented in the post-HITOC care of patients to avoid occupational exposure to cisplatin.
Blood Immune Cells as Biomarkers in Long-Term Surviving Patients with Advanced Non-Small-Cell Lung Cancer Undergoing a Combined Immune/Chemotherapy
Authors: Möller Miriam , Schütte Wolfgang , Turzer Steffi , Seliger Barbara , Riemann Dagmar
Published: October 2023

An important challenge remains in identifying the baseline characteristics of cancer patients who will mostly benefit from immune checkpoint inhibitor (ICI) therapies. Furthermore, biomarkers could help in the choice of an optimal therapy duration after a primary therapy response. In this pilot study, the time courses of four different immune cell parameters were followed in 12 patients with advanced non-small-cell lung cancer (NSCLC) undergoing ICI therapy combined with chemotherapy and surviving at least 12 months. Blood was collected at the time point of the first and third antibody administration, as well as after 12 months of patients’ survival. Using multi-color flow cytometry, two suppressive markers (neutrophil/lymphocyte ratio (NLR) and the frequency of circulating HLA-DRlow monocytes), as well as two markers of an ongoing immune response (6-Sulfo LacNAc (slan)+ non-classical monocytes and dendritic cell (DC) subtypes), were determined. In most of those who survived > 12 months, a low NLR and a low number of HLA-DRlow monocytes combined with clearly detectable numbers of slan+ non-classical monocytes and of DC subtypes were seen. Two of the patients had an increase in the suppressive markers paired with a decrease in slan+ non-classical monocytes and in DC subtypes, which, in at least one patient, was the correlate of an ongoing clinical progression. Our results implicate that the NLR, specific subtypes of monocytes, and the number of blood DCs might be useful predictive biomarkers for cancer patients during long-term treatment with ICI/chemotherapy.
Diagnostics and Therapeutics in Early Stage Breast Cancer Receiving Neoadjuvant Systemic Therapy
Authors: Belli Paolo , Palma Simone , Costantini Melania
Published: October 2023

Breast cancer (BC) remains a major challenge for oncology today, impacting the lives of countless individuals worldwide [...]
Genome-Wide DNA Methylation Profiling as Frontline Diagnostics for Central Nervous System Embryonal Tumors in Hong Kong
Authors: Tam Otto C. H. , Ho Ronnie S. L. , Chan Shing , Li Kay K. W. , Lam Tit-Leung , Cheung Elaine T. Y. , Cheung Oi-Yee , Ho Wilson W. S. , Cheng Kevin K. F. , Shing Matthew M. K. , Ku Dennis T. L. , Chung Brian H. Y. , Yang Wanling , Chan Godfrey C. F. , Ng Ho-Keung , Liu Anthony P. Y.
Published: October 2023

This paper examines the link between CNS tumor biology and heterogeneity and the use of genome-wide DNA methylation profiling as a clinical diagnostic platform. CNS tumors are the most common solid tumors in children, and their prognosis remains poor. This study retrospectively analyzed pediatric patients with CNS embryonal tumors in Hong Kong between 1999 and 2017, using data from the territory-wide registry and available formalin-fixed paraffin-embedded tumor tissue. After processing archival tumor tissue via DNA extraction, quantification, and methylation profiling, the data were analyzed by using the web-based DKFZ classifier (Molecular Neuropathology (MNP) 2.0 v11b4) and t-SNE analysis. Methylation profiles were deemed informative in 85 samples. Epigenetic data allowed molecular subgrouping and confirmed diagnosis in 65 samples, verified histologic diagnosis in 8, and suggested an alternative diagnosis in 12. This study demonstrates the potential of DNA methylation profiling in characterizing pediatric CNS embryonal tumors in a large cohort from Hong Kong, which should enable regional and international collaboration in future pediatric neuro-oncology research.
Pan-Cancer Analysis of Patient Tumor Single-Cell Transcriptomes Identifies Promising Selective and Safe Chimeric Antigen Receptor Targets in Head and Neck Cancer
Authors: Madan Sanna , Sinha Sanju , Chang Tiangen , Gutkind J. Silvio , Cohen Ezra E. W. , Schäffer Alejandro A. , Ruppin Eytan
Published: October 2023

Chimeric antigen receptor (CAR) T cell therapies have yielded transformative clinical successes for patients with blood tumors, but their full potential remains to be unleashed against solid tumors. One challenge is finding selective targets, which we define intuitively to be cell surface proteins that are expressed widely by cancer cells but minimally by healthy cells in the tumor microenvironment and other normal tissues. Analyzing patient tumor single-cell transcriptomics data, we first defined and quantified selectivity and safety scores of existing CAR targets for indications in which they are in clinical trials or approved. We then sought new candidate cell surface CAR targets that have better selectivity and safety scores than those currently being tested. Remarkably, in almost all cancer types, we could not find such better targets, testifying to the near optimality of the current target space. However, in human papillomavirus (HPV)-negative head and neck squamous cell carcinoma (HNSC), for which there is currently a dearth of existing CAR targets, we identified a total of twenty candidate novel CAR targets, five of which have both superior selectivity and safety scores. These newly identified cell surface targets lay a basis for future investigations that may lead to better CAR treatments in HNSC.
Focal Boost in Prostate Cancer Radiotherapy: A Review of Planning Studies and Clinical Trials
Authors: Zhao Yutong , Haworth Annette , Rowshanfarzad Pejman , Ebert Martin A.
Published: October 2023

Background: Focal boost radiotherapy was developed to deliver elevated doses to functional sub-volumes within a target. Such a technique was hypothesized to improve treatment outcomes without increasing toxicity in prostate cancer treatment. Purpose: To summarize and evaluate the efficacy and variability of focal boost radiotherapy by reviewing focal boost planning studies and clinical trials that have been published in the last ten years. Methods: Published reports of focal boost radiotherapy, that specifically incorporate dose escalation to intra-prostatic lesions (IPLs), were reviewed and summarized. Correlations between acute/late ≥G2 genitourinary (GU) or gastrointestinal (GI) toxicity and clinical factors were determined by a meta-analysis. Results: By reviewing and summarizing 34 planning studies and 35 trials, a significant dose escalation to the GTV and thus higher tumor control of focal boost radiotherapy were reported consistently by all reviewed studies. Reviewed trials reported a not significant difference in toxicity between focal boost and conventional radiotherapy. Acute ≥G2 GU and late ≥G2 GI toxicities were reported the most and least prevalent, respectively, and a negative correlation was found between the rate of toxicity and proportion of low-risk or intermediate-risk patients in the cohort. Conclusion: Focal boost prostate cancer radiotherapy has the potential to be a new standard of care.
Multitask Learning with Convolutional Neural Networks and Vision Transformers Can Improve Outcome Prediction for Head and Neck Cancer Patients
Authors: Starke Sebastian , Zwanenburg Alex , Leger Karoline , Lohaus Fabian , Linge Annett , Kalinauskaite Goda , Tinhofer Inge , Guberina Nika , Guberina Maja , Balermpas Panagiotis , Grün Jens von der , Ganswindt Ute , Belka Claus , Peeken Jan C. , Combs Stephanie E. , Boeke Simon , Zips Daniel , Richter Christian , Troost Esther G. C. , Krause Mechthild , Baumann Michael , Löck Steffen
Published: October 2023

Neural-network-based outcome predictions may enable further treatment personalization of patients with head and neck cancer. The development of neural networks can prove challenging when a limited number of cases is available. Therefore, we investigated whether multitask learning strategies, implemented through the simultaneous optimization of two distinct outcome objectives (multi-outcome) and combined with a tumor segmentation task, can lead to improved performance of convolutional neural networks (CNNs) and vision transformers (ViTs). Model training was conducted on two distinct multicenter datasets for the endpoints loco-regional control (LRC) and progression-free survival (PFS), respectively. The first dataset consisted of pre-treatment computed tomography (CT) imaging for 290 patients and the second dataset contained combined positron emission tomography (PET)/CT data of 224 patients. Discriminative performance was assessed by the concordance index (C-index). Risk stratification was evaluated using log-rank tests. Across both datasets, CNN and ViT model ensembles achieved similar results. Multitask approaches showed favorable performance in most investigations. Multi-outcome CNN models trained with segmentation loss were identified as the optimal strategy across cohorts. On the PET/CT dataset, an ensemble of multi-outcome CNNs trained with segmentation loss achieved the best discrimination (C-index: 0.29, 95% confidence interval (CI): 0.22–0.36) and successfully stratified patients into groups with low and high risk of disease progression (p=0.003). On the CT dataset, ensembles of multi-outcome CNNs and of single-outcome ViTs trained with segmentation loss performed best (C-index: 0.26 and 0.26, CI: 0.18–0.34 and 0.18–0.35, respectively), both with significant risk stratification for LRC in independent validation (p=0.002 and p=0.011). Further validation of the developed multitask-learning models is planned based on a prospective validation study, which has recently completed recruitment.
Mannose-Binding Lectin 2 as a Potential Therapeutic Target for Hepatocellular Carcinoma: Multi-Omics Analysis and Experimental Validation
Authors: Liao Hangyu , Yang Jun , Xu Yuyan , Xie Juncheng , Li Ke , Chen Kunling , Pei Jingyuan , Luo Qiong , Pan Mingxin
Published: October 2023

Mannose-binding lectin 2 (MBL2), a member of the multimeric lectin family, is crucial in immune regulation and tumor development. MBL2 gene polymorphisms are associated with the risk and prognosis of various tumors, including hepatocellular carcinoma (HCC). Its functional role in HCC remains largely unclear. In this study, we aimed to identify whether MBL2 is a key regulator and a potential therapeutic target for HCC. A bioinformatics analysis revealed close relationships among MBL2 downregulation, the tumor-associated proliferation and metastasis pathway, and tumor immunosuppressive microenvironments. Lower expression of MBL2 in HCC patients was linked to an unfavorable prognosis. A cell counting kit-8 assay, colony formation assay, transwell migration assay, and wound healing assay further confirmed that the overexpression of MBL2 could directly inhibit the proliferation and metastasis of HCC. Moreover, MBL2 expression was regulated by miR-34c-3p, as confirmed by the dual-luciferase reporter assay, thereby demonstrating tumor progression in HCC cells. Thus, our study offers the first comprehensive confirmation of the role of MBL2 in the development of HCC through multi-omics analysis and experimental validation. Furthermore, miR-34c-3p was found to be an upstream mechanism of the downregulation of MBL2 expression and could be a promising therapeutic target, expanding treatment options for patients with HCC.
Influence of Neoadjuvant Chemotherapy on Survival Outcomes of Radical Cystectomy in Pathologically Proven Positive and Negative Lymph Nodes
Authors: Kaczmarek Krystian , Małkiewicz Bartosz , Skonieczna-Żydecka Karolina , Lemiński Artur
Published: October 2023

Patients receiving neoadjuvant chemotherapy (NAC) prior to radical cystectomy (RC) typically show better survival outcomes than those undergoing immediate surgery for muscle-invasive bladder cancer. However, most studies have not considered the lymph node (LN) status when evaluating NAC’s survival benefits. This study sought to delineate the impact of NAC on patients based on their pathologically determined LN status at the time of RC. We examined data from 1395 patients treated at two departments between 1991 and 2022. Of them, 481 had positive LNs. A comparison of overall survival (OS) outcomes revealed that patients without LN involvement ((y)pN0) benefited from NAC with a hazard ratio (HR) of 0.692 (95% confidence interval [CI] 0.524–0.915). In contrast, patients with (y)pN+ showed no improvement with NAC (HR 0.927, 95%CI 0.713–1.205). Notably, patients treated with NAC for stage <ypT2ypN+ tumours experienced reduced OS compared to their counterparts who did not receive NAC. The HR was 3.111 (95%CI 1.249–7.746). Given that persistent nodal disease after NAC correlates with a worse prognosis, additional post-operative treatments should be considered.