bluuebunny/crossref_metadata_2025 huggingface dataset:
The Effect of Greening Layout on Microclimate in Urban Residential Areas in Hot Summer–Cold Winter Zones
Authors: Lu Fangqi , Gao Yafeng , Jiang Lina , Chen Yangyang , Hao Zhongyu
Published: December 2023

Appropriate greening design can enhance the microclimate of residential areas. This study investigated different greening cases for residential buildings in hot summer–cold winter zones. Four sorts of greening layouts were tested in a residential area in Chongqing, China. Arbor–grass mix and arbor–shrub–grass mix showed effective cooling and humidifying effects, and were chosen for further study using the ENVI-met model. The simulations were conducted in Chongqing, comparing sixteen greening cases for determinant and enclosed building forms. Results indicate that the greening design for determinant layout should give priority to ensuring the greening area and shortening the distance from the sidewalk. While enclosed layout should concentrate greening in dense populations, using arbor–shrub–grass mix to improve the wind environment. In cases where the distribution of arbors and shrubs covers a ratio of 7:4, constituting 30% of the overall green space, there is a reduction in environmental temperature by 1.4 °C and in PET by 4.8 °C. This study provides the optimal greening layout for two types of residential areas in China’s hot summer–cold winter zones, guiding landscape construction in these residential areas to optimize the microclimate.
On Boundary Controllability for the Higher-Order Nonlinear Schrödinger Equation
Authors: Faminskii Andrei V.
Published: December 2023

A control problem with final overdetermination is considered for the higher-order nonlinear Schrödinger equation on a bounded interval. The boundary condition on the space derivative is chosen as the control. Results on the global existence of solutions under small input data are established.
Immune Escape in Glioblastoma: Mechanisms of Action and Implications for Immune Checkpoint Inhibitors and CAR T-Cell Therapy
Authors: Yu Catherine , Hsieh Kristin , Cherry Daniel R. , Nehlsen Anthony D. , Resende Salgado Lucas , Lazarev Stanislav , Sindhu Kunal K.
Published: December 2023

Glioblastoma, the most common primary brain cancer in adults, is characterized by a poor prognosis and resistance to standard treatments. The advent of immunotherapy has revolutionized the treatment of several cancers in recent years but has failed to demonstrate benefit in patients with glioblastoma. Understanding the mechanisms by which glioblastoma exerts tumor-mediated immune suppression in both the tumor microenvironment and the systemic immune landscape is a critical step towards developing effective immunotherapeutic strategies. In this review, we discuss the current understanding of immune escape mechanisms in glioblastoma that compromise the efficacy of immunotherapies, with an emphasis on immune checkpoint inhibitors and chimeric antigen receptor T-cell therapy. In parallel, we review data from preclinical studies that have identified additional therapeutic targets that may enhance overall treatment efficacy in glioblastoma when administered alongside existing immunotherapies.
Vesicular Trafficking, a Mechanism Controlled by Cascade Activation of Rab Proteins: Focus on Rab27
Authors: Menaceur Camille , Dusailly Océane , Gosselet Fabien , Fenart Laurence , Saint-Pol Julien
Published: December 2023

Vesicular trafficking is essential for the cell to internalize useful proteins and soluble substances, for cell signaling or for the degradation of pathogenic elements such as bacteria or viruses. This vesicular trafficking also enables the cell to engage in secretory processes for the elimination of waste products or for the emission of intercellular communication vectors such as cytokines, chemokines and extracellular vesicles. Ras-related proteins (Rab) and their effector(s) are of crucial importance in all of these processes, and mutations/alterations to them have serious pathophysiological consequences. This review presents a non-exhaustive overview of the role of the major Rab involved in vesicular trafficking, with particular emphasis on their involvement in the biogenesis and secretion of extracellular vesicles, and on the role of Rab27 in various pathophysiological processes. Therefore, Rab and their effector(s) are central therapeutic targets, given their involvement in vesicular trafficking and their importance for cell physiology.
Low-Dose Ionizing Radiation-Crosslinking Immunoprecipitation (LDIR-CLIP) Identified Irradiation-Sensitive RNAs for RNA-Binding Protein HuR-Mediated Decay
Authors: Lee Ji Won , Mun Hyejin , Kim Jeong-Hyun , Ko Seungbeom , Kim Young-Kook , Shim Min Ji , Kim Kyungmin , Ho Chul Woong , Park Hyun Bong , Kim Meesun , Lee Chaeyoung , Choi Si Ho , Kim Jung-Woong , Jeong Ji-Hoon , Yoon Je-Hyun , Min Kyung-Won , Son Tae Gen
Published: December 2023

Although ionizing radiation (IR) is widely used for therapeutic and research purposes, studies on low-dose ionizing radiation (LDIR) are limited compared with those on other IR approaches, such as high-dose gamma irradiation and ultraviolet irradiation. High-dose IR affects DNA damage response and nucleotide–protein crosslinking, among other processes; however, the molecular consequences of LDIR have been poorly investigated. Here, we developed a method to profile RNA species crosslinked to an RNA-binding protein, namely, human antigen R (HuR), using LDIR and high-throughput RNA sequencing. The RNA fragments isolated via LDIR-crosslinking and immunoprecipitation sequencing were crosslinked to HuR and protected from RNase-mediated digestion. Upon crosslinking HuR to target mRNAs such as PAX6, ZFP91, NR2F6, and CAND2, the transcripts degraded rapidly in human cell lines. Additionally, PAX6 and NR2F6 downregulation mediated the beneficial effects of LDIR on cell viability. Thus, our approach provides a method for investigating post-transcriptional gene regulation using LDIR.
Characteristic Binding Landscape of Estrogen Receptor-α36 Protein Enhances Promising Cancer Drug Design
Authors: Adewumi Adeniyi T. , Mosebi Salerwe
Published: December 2023

Breast cancer (BC) remains the most common cancer among women worldwide, and estrogen receptor-α expression is a critical diagnostic factor for BC. Estrogen receptor (ER-α36) is a dominant-negative effector of ER-α66-mediated estrogen-responsive gene pathways. ER-α36 is a novel target that mediates the non-genomic estrogen signaling pathway. However, the crystallized structure of ER-α36 remains unavailable for molecular studies. ER-positive and triple-negative BC tumors aggressively resist the FDA-approved drugs; therefore, highly potent structure-based inhibitors with preeminent benefits over toxicity will preferably replace the current BC treatment. Broussoflanol B (BFB), a B. papyrifera bark compound, exhibits potent growth inhibitory activity in ER-negative BC cells by inducing cell cycle arrest. For the first time, we unravel the comparative dynamic events of the enzymes’ structures and the binding mechanisms of BFB when bound to the ER-α36 and ER-α66 ligand-binding domain using an all-atom molecular dynamics simulations approach and MM/PBSA-binding-free energy calculations. The dynamic findings have revealed that ER-α36 and ER-α66 LBD undergo timescale “coiling”, opening and closing conformations favoring the high-affinity BFB-bound ER-α36 (ΔG = −52.57 kcal/mol) compared to the BFB-bound ER-α66 (ΔG = −42.41 kcal/mol). Moreover, the unbound (1.260 Å) and bound ER-α36 (1.182 Å) exhibit the highest flexibilities and atomistic motions relative to the ER-α66 systems. The RMSF (Å) of the unbound ER-α36 and ER-α66 exhibit lesser stabilities than the BFB-bound systems, resulting in higher structural flexibilities and atomistic motions than the bound variants. These findings present a model that describes the mechanisms by which the BFB compound induces downregulation-accompanied cell cycle arrest at the Gap0 and Gap1 phases.
Impaired Autophagic Clearance with a Gain-of-Function Variant of the Lysosomal Cl−/H+ Exchanger ClC-7
Authors: Bose Shroddha , de Heus Cecilia , Kennedy Mary E. , Wang Fan , Jentsch Thomas J. , Klumperman Judith , Stauber Tobias
Published: December 2023

ClC-7 is a ubiquitously expressed voltage-gated Cl−/H+ exchanger that critically contributes to lysosomal ion homeostasis. Together with its β-subunit Ostm1, ClC-7 localizes to lysosomes and to the ruffled border of osteoclasts, where it supports the acidification of the resorption lacuna. Loss of ClC-7 or Ostm1 leads to osteopetrosis accompanied by accumulation of storage material in lysosomes and neurodegeneration. Interestingly, not all osteopetrosis-causing CLCN7 mutations from patients are associated with a loss of ion transport. Some rather result in an acceleration of voltage-dependent ClC-7 activation. Recently, a gain-of-function variant, ClC-7Y715C, that yields larger ion currents upon heterologous expression, was identified in two patients with neurodegeneration, organomegaly and albinism. However, neither the patients nor a mouse model that carried the equivalent mutation developed osteopetrosis, although expression of ClC-7Y715C induced the formation of enlarged intracellular vacuoles. Here, we investigated how, in transfected cells with mutant ClC-7, the substitution of this tyrosine impinged on the morphology and function of lysosomes. Combinations of the tyrosine mutation with mutations that either uncouple Cl− from H+ counter-transport or strongly diminish overall ion currents were used to show that increased ClC-7 Cl−/H+ exchange activity is required for the formation of enlarged vacuoles by membrane fusion. Degradation of endocytosed material was reduced in these compartments and resulted in an accumulation of lysosomal storage material. In cells expressing the ClC-7 gain-of-function mutant, autophagic clearance was largely impaired, resulting in a build-up of autophagic material.
Using Selective Enzymes to Measure Noncanonical DNA Building Blocks: dUTP, 5-Methyl-dCTP, and 5-Hydroxymethyl-dCTP
Authors: Surányi Éva Viola , Perey-Simon Viktória , Hirmondó Rita , Trombitás Tamás , Kazzazy Latifa , Varga Máté , Vértessy Beáta G. , Tóth Judit
Published: December 2023

Cells maintain a fine-tuned balance of deoxyribonucleoside 5′-triphosphates (dNTPs), a crucial factor in preserving genomic integrity. Any alterations in the nucleotide pool’s composition or chemical modifications to nucleotides before their incorporation into DNA can lead to increased mutation frequency and DNA damage. In addition to the chemical modification of canonical dNTPs, the cellular de novo dNTP metabolism pathways also produce noncanonical dNTPs. To keep their levels low and prevent them from incorporating into the DNA, these noncanonical dNTPs are removed from the dNTP pool by sanitizing enzymes. In this study, we introduce innovative protocols for the high-throughput fluorescence-based quantification of dUTP, 5-methyl-dCTP, and 5-hydroxymethyl-dCTP. To distinguish between noncanonical dNTPs and their canonical counterparts, specific enzymes capable of hydrolyzing either the canonical or noncanonical dNTP analogs are employed. This approach provides a more precise understanding of the composition and noncanonical constituents of dNTP pools, facilitating a deeper comprehension of DNA metabolism and repair. It is also crucial for accurately interpreting mutational patterns generated through the next-generation sequencing of biological samples.
Optimized Copper-Based Microfeathers for Glucose Detection
Authors: Guati Carlota , Gómez-Coma Lucía , Fallanza Marcos , Ortiz Inmaculada
Published: December 2023

Diabetes is expected to rise substantially by 2045, prompting extensive research into accessible glucose electrochemical sensors, especially those based on non-enzymatic materials. In this context, advancing the knowledge of stable metal-based compounds as alternatives to non-enzymatic sensors becomes a scientific challenge. Nonetheless, these materials have encountered difficulties in maintaining stable responses under physiological conditions. This work aims to advance knowledge related to the synthesis and characterization of copper-based electrodes for glucose detection. The microelectrode presented here exhibits a wide linear range and a sensitivity of 1009 µA∙cm−2∙mM−1, overperfoming the results reported in literature so far. This electrode material has also demonstrated outstanding results in terms of reproducibility, repeatability, and stability, thereby meeting ISO 15197:2015 standards. Our study guides future research on next-generation sensors that combine copper with other materials to enhance activity in neutral media.
Differential Effects of Paraquat, Rotenone, and MPTP on Cellular Bioenergetics of Undifferentiated and Differentiated Human Neuroblastoma Cells
Authors: Elmorsy Ekramy , Al-Ghafari Ayat , Al Doghaither Huda , Hashish Sara , Salama Mohamed , Mudyanselage Anusha W. , James Lipta , Carter Wayne G.
Published: December 2023

Paraquat (PQ), rotenone (RO), and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) are neurotoxicants that can damage human health. Exposure to these neurotoxicants has been linked to neurodegeneration, particularly Parkinson’s disease. However, their mechanisms of action have not been fully elucidated, nor has the relative vulnerability of neuronal subtypes to their exposures. To address this, the current study investigated the cytotoxic effects of PQ, RO, and MPTP and their relative effects on cellular bioenergetics and oxidative stress on undifferentiated human neuroblastoma (SH-SY5Y) cells and those differentiated to dopaminergic (DA) or cholinergic (CH) phenotypes. The tested neurotoxicants were all cytotoxic to the three cell phenotypes that correlated with both concentration and exposure duration. At half-maximal effective concentrations (EC50s), there were significant reductions in cellular ATP levels and reduced activity of the mitochondrial complexes I and III, with a parallel increase in lactate production. PQ at 10 µM significantly decreased ATP production and mitochondrial complex III activity only in DA cells. RO was the most potent inhibitor of mitochondrial complex 1 and did not inhibit mitochondrial complex III even at concentrations that induced a 50% loss of cell viability. MPTP was the most potent toxicant in undifferentiated cells. All neurotoxicants significantly increased reactive oxygen species, lipid peroxidation, and nuclear expression of Nrf2, with a corresponding inhibition of the antioxidant enzymes catalase and superoxide dismutase. At a 10 µM exposure to PQ or RO, oxidative stress biomarkers were significant in DA cells. Collectively, this study underscores the importance of mitochondrial dysfunction and oxidative stress in PQ, RO, and MPTP-induced cytotoxicity and that neuronal phenotypes display differential vulnerability to these neurotoxicants.
Technostress, Quality of Work Life, and Job Performance: A Moderated Mediation Model
Authors: Saleem Farida , Malik Muhammad Imran
Published: December 2023

This study examines the effect of technostress on teachers’ quality of work life and job performance. A moderated mediation model is proposed and tested based on the transactional model of stress and coping. This study proposes organizational flexibility as the boundary condition—a first-level moderator—and quality of work life as the explanatory variable. A sample of 199 university teachers who worked from home or used the hybrid teaching mode was selected. Data were collected through closed-ended questionnaires. Structural equation modeling (SEM) and the Hayes PROCESS Macro (extension in SPSS) were used for hypothesis testing. The results found that the three dimensions of technostress (Techno complexity, Techno invasion, and Techno overload) negatively and significantly affect teachers’ quality of work life. However, there are significant positive direct effects of these three dimensions of technostress on employee performance and significant negative indirect effects on performance through quality of work life. Organizational flexibility acts as a significant moderator, where a low value of organizational flexibility enhances the negative relationship between technostress and quality of work life. In contrast, high values of organizational flexibility convert the significant negative relationship into an insignificant impact. The university management must take measures to overcome technostress among teachers by showing flexibility.
Study of the Nonuniform Consolidation Characteristics of Soft Soils Using a Novel Model
Authors: Zhou Yuefu , Han Wenlong , Su Dong , Chen Xiangsheng
Published: December 2023

The degree of soil nonuniformity consolidation varies continuously with the passage of consolidation time and is accompanied by nonlinear alterations in soil parameters. Existing theoretical models often assume a constant relationship between the parameters of the two soil layers, failing to consider the effect of nonuniform consolidation. This assumption does not align with real-world conditions and can lead to significant errors in calculation results. Hence, this study aims to investigate the dynamic changes in soil undergoing nonuniform consolidation and develop a mathematical model that accounts for this phenomenon. Based on the large-strain and double-layer models, an improved consolidation model was proposed, which considers nonuniform variations in consolidation with a vertical drain and corrections to calculations under the influence of the nonlinear relationships of soil parameters. The proposed improved model was validated by comparison with field test data, and the results were compared with those of the classical model. Finally, the effects of different consolidation parameters on consolidation behavior were investigated. The research is a reliable calculation method that incorporates the dynamic nonuniform changes in consolidated soil, enabling more accurate predictions of consolidation of foundations treated by vertical drains.
Research on the Characteristics of Urban Building Cluster Wind Field Based on UAV Wind Measurement
Authors: Pu Ou , Yuan Boqiu , Li Zhengnong , Bao Terigen , Chen Zheng , Yang Liwei , Qin Hua , Li Zhen
Published: December 2023

An innovative approach for measuring wind fields in urban building clusters using Unmanned Aerial Vehicles (UAVs) is presented. This method captures the distribution of wind fields within clusters. The results indicate that building architecture has a significant influence on wind flow characteristics at 15 m and 25 m height levels. Particularly, areas adjacent to the buildings and the wake section exhibit notable variations in wind speed and turbulence intensity compared to the incoming flow. The regions most affected include the areas flanking the buildings on either side and the intermediate section of the wake. The flow separation and convergence of incoming wind from the windward sides of the buildings notably amplify the wind load, resulting in a significant shift in wind speed and turbulence intensity within pedestrian pathways. The use of UAVs for wind measurements enables a flexible and efficient assessment of urban wind fields. These findings pave the way for further research into wind field measurements in urban architecture and a better understanding of the interference effects of buildings.
Deep-Learning- and Unmanned Aerial Vehicle-Based Structural Crack Detection in Concrete
Authors: Jin Tao , Zhang Wen , Chen Chunlai , Chen Bin , Zhuang Yizhou , Zhang He
Published: December 2023

Deep-learning- and unmanned aerial vehicle (UAV)-based methods facilitate structural crack detection for tall structures. However, contemporary datasets are generally established using images taken with handheld or vehicle-mounted cameras. Thus, these images might be different from those taken by UAVs in terms of resolution and lighting conditions. Considering the difficulty and complexity of establishing a crack image dataset, making full use of the current datasets can help reduce the shortage of UAV-based crack image datasets. Therefore, the performance evaluation of existing crack image datasets in training deep neural networks (DNNs) for crack detection in UAV images is essential. In this study, four DNNs were trained with different architectures based on a publicly available dataset and tested using a small UAV-based crack image dataset with 648 +pixel-wise annotated images. These DNNs were first tested using the four indices of precision, recall, mIoU, and F1, and image tests were also conducted for intuitive comparison. Moreover, a field experiment was carried out to verify the performance of the trained DNNs in detecting cracks from raw UAV structural images. The results indicate that the existing dataset can be useful to train DNNs for crack detection from UAV images; the TransUNet achieved the best performance in detecting all kinds of structural cracks.
Behavior of Confined Self-Compacting Concrete under Compression at Elevated Temperatures
Authors: Ulla Khan Athiq , Sateesh Kumar Nanjundaswamy , Bahrami Alireza , Özkılıç Yasin Onuralp , Imran Mohammed , Althaqafi Essam , Islam Saiful
Published: December 2023

The performance of self-compacting concrete (SCC) is gaining popularity in construction due to its exceptional strength and durability. However, the properties of combined steel and concrete at elevated temperatures lack experimental data from previous research. This study aimed to investigate the behavior of the SCC core with a steel tube at ambient and elevated temperatures varying from 100 °C to 800 °C with 100 °C intervals for each test specimen. Tests were conducted on circular steel tubes filled with SCC for different grades (M25, M30, and M40) under compression at elevated temperatures. Experimental observations revealed that the stress–strain curve increased with increasing the cross-sectional area and grade of concrete. However, increasing the temperature and length-to-diameter ratio reduced the stress–strain curve. At elevated temperatures, confined SCC experienced a smaller decrease in the overall modulus of elasticity when compared to unconfined concrete. Within the compressive elastic region (from 30 °C to 400 °C), there was a significant relationship between lateral strain and longitudinal strain, which was followed by a sudden increase beyond 400 °C. Equations for various design parameters were proposed based on the peak load and confinement factor of confined SCC-filled steel tubes (SCCFSTs) via multiple regression. Moreover, this study developed load–axial shortening curves, identifying significant properties such as the yield strength of confined SCCFSTs, including the load-carrying capacity. The predicted numerical analysis results were well aligned with the experimental results, and the findings contributed valuable insights for designing resilient and durable combined SCC and steel tube infrastructures.
Seismic Repair Cost-Based Assessment for Low-Rise Reinforced Concrete Archetype Buildings through Incremental Dynamic Analysis
Authors: Chicaiza-Fuentes Juan Patricio , Haro-Baez Ana Gabriela
Published: December 2023

This study presents the performance-based seismic assessment of low-rise reinforced concrete archetype buildings, considering repair costs for ordinary moment-resistant frames (OMF) and dual systems consisting of OMF plus special shear walls (SSW). Historically, the OMF systems, conceived for residential purposes in Ecuador resulting from informal construction, have reported poor responses under seismic forces. This study analyzes damage levels through fragility curves as a function of the maximum global drift reached through incremental dynamic analysis. For this, two archetypes with OMF and two with a similar configuration, including structural walls, are modeled to define a loss function and annual collapse probabilities. As a result, it is noted that systems with structural walls significantly reduce repair costs by between 75 and 90% of the total cost of the building, and prevent collapse. Systems with ordinary moment frames report total losses, implying their use should be limited in areas of high seismicity.
Does the Simultaneous Introduction of Several Pharmaceuticals in the Post-Lenalidomide Era Translate to Better Outcomes in Relapse Refractory Multiple Myeloma? Findings from the Real-World Innovation in Multiple Myeloma (REAL IMM) Study
Authors: Petrakis Ioannis , Kontogiorgis Christos , Nena Evangelia , Delimpasi Sosana , Loutsidi Natasa E. , Spanoudakis Emmanouil , Intzes Stergios , Misidou Christina , Symeonidou Marianthi , Giannakoulas Nikolaos , Constantinidis Theodoros C. , Terpos Evangelos
Published: December 2023

Newer methodologies are needed to assess the real-world comparative effectiveness of a “generation” of pharmaceutical innovation versus the prior standard of care. This chart review study aimed to first evaluate the cumulative clinical benefits of pharmaceutical innovation in everyday relapse/refractory multiple myeloma before analyzing findings in the context of respective real-world outcomes from the bortezomib/lenalidomide era. Study endpoints included the 52-week PFS rate in second and third line of therapy (LOT), mPFS-2 across the first and second LOT, the ORR, reasons for discontinuation, and the treatment duration per therapeutic algorithm. Data from 107 patients were collected. The median follow-up was 2.0 years. Of the subjects who met the selection criteria for the second LOT, 72.2% maintained the PFS at 52 weeks. In the third-line setting, the PFS rate at 52 weeks was 63.5%. The mPFS across the first and second, the second, and the third LOTs were 26, 17, and 15 months, respectively. The ORR was 76.1% in the second and 69.7% in the third LOT. After non-response or progression, the main reason for drug discontinuation was treatment intolerability. The second-line ORR and the 52-week PFS rate were similar to previous real-world findings from the bortezomib/lenalidomide era. The cumulative mPFS across the second and third LOTs was higher than the respective mPFS across the first and second LOTs. Despite its limitations, the methodology and findings from this study may be used in future clinical and economic evaluations across all hematological malignancies.
Navigating Tumour Microenvironment and Wnt Signalling Crosstalk: Implications for Advanced Cancer Therapeutics
Authors: Peri Shraddha Shravani , Narayanaa Y Krithicaa , Hubert Therese Deebiga , Rajaraman Roshini , Arfuso Frank , Sundaram Sandhya , Archana B. , Warrier Sudha , Dharmarajan Arun , Perumalsamy Lakshmi R.
Published: December 2023

Cancer therapeutics face significant challenges due to drug resistance and tumour recurrence. The tumour microenvironment (TME) is a crucial contributor and essential hallmark of cancer. It encompasses various components surrounding the tumour, including intercellular elements, immune system cells, the vascular system, stem cells, and extracellular matrices, all of which play critical roles in tumour progression, epithelial–mesenchymal transition, metastasis, drug resistance, and relapse. These components interact with multiple signalling pathways, positively or negatively influencing cell growth. Abnormal regulation of the Wnt signalling pathway has been observed in tumorigenesis and contributes to tumour growth. A comprehensive understanding and characterisation of how different cells within the TME communicate through signalling pathways is vital. This review aims to explore the intricate and dynamic interactions, expressions, and alterations of TME components and the Wnt signalling pathway, offering valuable insights into the development of therapeutic applications.
Descriptive Epidemiology of Melanoma Diagnosed between 2010 and 2014 in a Colombian Cancer Registry and a Call for Improving Available Data on Melanoma in Latin America
Authors: de Vries Esther , Uribe Claudia , Beltrán Rodríguez Claudia Catalina , Caparros Alfredo , Meza Erika , Gil Fabian
Published: December 2023

We aimed to improve the available information on morphology and stage for cutaneous melanoma in the population-based cancer registry of the Bucaramanga Metropolitan Area in Colombia. The incidence and survival rates and the distribution of melanoma patients by age, gender, anatomical subsite, and histological subtype were calculated. All 113 melanoma patients (median age 61) were followed up (median time 7.4 years). This exercise (filling in missing information in the registry by manual search of patient clinical record and other available information) yielded more identified invasive melanomas and cases with complete information on anatomical localization and stage. Age-standardized incidence and mortality rates were 1.86 and 1.08, being slightly higher for males. Most melanomas were localized on the lower limbs, followed by the trunk. For 35% of all melanomas, the morphological subtype remained unknown. Most of the remaining melanomas were nodular and acral lentiginous melanomas. Overall global and relative 5-year survival was 61.6% and 71.3%, respectively, with poorer survival for males than females. Melanomas on the head and neck and unspecified anatomical sites had the worst survival. Patients without stage information in their medical files had excellent survival, unlike patients for whom medical files were no longer available. This study shows the possibility of improving data availability and the importance of good quality population-based data.
The Role of Exercise in Cancer-Related Sarcopenia and Sarcopenic Obesity
Authors: Papadopetraki Argyro , Giannopoulos Antonios , Maridaki Maria , Zagouri Flora , Droufakou Stavroula , Koutsilieris Michael , Philippou Anastassios
Published: December 2023

One of the most common adverse effects of cancer and its therapeutic strategies is sarcopenia, a condition which is characterised by excess muscle wasting and muscle strength loss due to the disrupted muscle homeostasis. Moreover, cancer-related sarcopenia may be combined with the increased deposition of fat mass, a syndrome called cancer-associated sarcopenic obesity. Both clinical conditions have significant clinical importance and can predict disease progression and survival. A growing body of evidence supports the claim that physical exercise is a safe and effective complementary therapy for oncology patients which can limit the cancer- and its treatment-related muscle catabolism and promote the maintenance of muscle mass. Moreover, even after the onset of sarcopenia, exercise interventions can counterbalance the muscle mass loss and improve the clinical appearance and quality of life of cancer patients. The aim of this narrative review was to describe the various pathophysiological mechanisms, such as protein synthesis, mitochondrial function, inflammatory response, and the hypothalamic–pituitary–adrenal axis, which are regulated by exercise and contribute to the management of sarcopenia and sarcopenic obesity. Moreover, myokines, factors produced by and released from exercising muscles, are being discussed as they appear to play an important role in mediating the beneficial effects of exercise against sarcopenia.
Graph Neural Networks in Cancer and Oncology Research: Emerging and Future Trends
Authors: Gogoshin Grigoriy , Rodin Andrei S.
Published: December 2023

Next-generation cancer and oncology research needs to take full advantage of the multimodal structured, or graph, information, with the graph data types ranging from molecular structures to spatially resolved imaging and digital pathology, biological networks, and knowledge graphs. Graph Neural Networks (GNNs) efficiently combine the graph structure representations with the high predictive performance of deep learning, especially on large multimodal datasets. In this review article, we survey the landscape of recent (2020–present) GNN applications in the context of cancer and oncology research, and delineate six currently predominant research areas. We then identify the most promising directions for future research. We compare GNNs with graphical models and “non-structured” deep learning, and devise guidelines for cancer and oncology researchers or physician-scientists, asking the question of whether they should adopt the GNN methodology in their research pipelines.
The Future of Minimally Invasive Capsule Panendoscopy: Robotic Precision, Wireless Imaging and AI-Driven Insights
Authors: Mascarenhas Miguel , Martins Miguel , Afonso João , Ribeiro Tiago , Cardoso Pedro , Mendes Francisco , Andrade Patrícia , Cardoso Helder , Ferreira João , Macedo Guilherme
Published: December 2023

In the early 2000s, the introduction of single-camera wireless capsule endoscopy (CE) redefined small bowel study. Progress continued with the development of double-camera devices, first for the colon and rectum, and then, for panenteric assessment. Advancements continued with magnetic capsule endoscopy (MCE), particularly when assisted by a robotic arm, designed to enhance gastric evaluation. Indeed, as CE provides full visualization of the entire gastrointestinal (GI) tract, a minimally invasive capsule panendoscopy (CPE) could be a feasible alternative, despite its time-consuming nature and learning curve, assuming appropriate bowel cleansing has been carried out. Recent progress in artificial intelligence (AI), particularly in the development of convolutional neural networks (CNN) for CE auxiliary reading (detecting and diagnosing), may provide the missing link in fulfilling the goal of establishing the use of panendoscopy, although prospective studies are still needed to validate these models in actual clinical scenarios. Recent CE advancements will be discussed, focusing on the current evidence on CNN developments, and their real-life implementation potential and associated ethical challenges.
Lipophilic Statins Eliminate Senescent Endothelial Cells by inducing Anoikis-Related Cell Death
Authors: Belakova Barbora , Wedige Nicholas K. , Awad Ezzat M. , Hess Simon , Oszwald André , Fellner Marlene , Khan Shafaat Y. , Resch Ulrike , Lipovac Markus , Šmejkal Karel , Uhrin Pavel , Breuss Johannes M.
Published: December 2023

Pre-clinical studies from the recent past have indicated that senescent cells can negatively affect health and contribute to premature aging. Targeted eradication of these cells has been shown to improve the health of aged experimental animals, leading to a clinical interest in finding compounds that selectively eliminate senescent cells while sparing non-senescent ones. In our study, we identified a senolytic capacity of statins, which are lipid-lowering drugs prescribed to patients at high risk of cardiovascular events. Using two different models of senescence in human vascular endothelial cells (HUVECs), we found that statins preferentially eliminated senescent cells, while leaving non-senescent cells unharmed. We observed that the senolytic effect of statins could be negated with the co-administration of mevalonic acid and that statins induced cell detachment leading to anoikis-like apoptosis, as evidenced by real-time visualization of caspase-3/7 activation. Our findings suggest that statins possess a senolytic property, possibly also contributing to their described beneficial cardiovascular effects. Further studies are needed to explore the potential of short-term, high-dose statin treatment as a candidate senolytic therapy.
Therapeutic Monoclonal Antibodies against Cancer: Present and Future
Authors: Delgado Marisa , Garcia-Sanz Jose A.
Published: December 2023

A series of monoclonal antibodies with therapeutic potential against cancer have been generated and developed. Ninety-one are currently used in the clinics, either alone or in combination with chemotherapeutic agents or other antibodies, including immune checkpoint antibodies. These advances helped to coin the term personalized medicine or precision medicine. However, it seems evident that in addition to the current work on the analysis of mechanisms to overcome drug resistance, the use of different classes of antibodies (IgA, IgE, or IgM) instead of IgG, the engineering of the Ig molecules to increase their half-life, the acquisition of additional effector functions, or the advantages associated with the use of agonistic antibodies, to allow a broad prospective usage of precision medicine successfully, a strategy change is required. Here, we discuss our view on how these strategic changes should be implemented and consider their pros and cons using therapeutic antibodies against cancer as a model. The same strategy can be applied to therapeutic antibodies against other diseases, such as infectious or autoimmune diseases.
Resveratrol’s Impact on the Chondrogenic Reagents’ Effects in Cell Sheet Cultures of Wharton’s Jelly-Derived MSCs
Authors: Kurenkova Anastasiia D. , Presniakova Viktoria S. , Mosina Zlata A. , Kibirskiy Pavel D. , Romanova Irina A. , Tugaeva Gilyana K. , Kosheleva Nastasia V. , Vinogradov Kirill S. , Kostjuk Sergei V. , Kotova Svetlana L. , Rochev Yury A. , Medvedeva Ekaterina V. , Timashev Peter S.
Published: December 2023

Human Wharton’s jelly mesenchymal stem cells (hWJ-MSCs) are of great interest in tissue engineering. We obtained hWJ-MSCs from four patients, and then we stimulated their chondrogenic phenotype formation in vitro by adding resveratrol (during cell expansion) and a canonical Wnt pathway activator, LiCl, as well as a Rho-associated protein kinase inhibitor, Y27632 (during differentiation). The effects of the added reagents on the formation of hWJ-MSC sheets destined to repair osteochondral injuries were investigated. Three-dimensional hWJ-MSC sheets grown on P(NIPAM-co-NtBA)-based matrices were characterized in vitro and in vivo. The combination of resveratrol and LiCl showed effects on hWJ-MSC sheets similar to those of the basal chondrogenic medium. Adding Y27632 decreased both the proportion of hypertrophied cells and the expression of the hyaline cartilage markers. In vitro, DMSO was observed to impede the effects of the chondrogenic factors. The mouse knee defect model experiment revealed that hWJ-MSC sheets grown with the addition of resveratrol and Y27632 were well integrated with the surrounding tissues; however, after 3 months, the restored tissue was identical to that of the naturally healed cartilage injury. Thus, the combination of chondrogenic supplements may not always have additive effects on the progress of cell culture and could be neutralized by the microenvironment after transplantation.
Epithelial Barrier Dysfunction in Diarrhea-Predominant Irritable Bowel Syndrome (IBS-D) via Downregulation of Claudin-1
Authors: Awad Karem , Barmeyer Christian , Bojarski Christian , Nagel Oliver , Lee In-Fah M. , Schweiger Michal R. , Schulzke Jörg-Dieter , Bücker Roland
Published: December 2023

Background: In patients with diarrhea-predominant irritable bowel syndrome (IBS-D), the diarrheal mechanisms are largely unknown, and they were examined in this study on colon biopsies. Methods: Electrophysiological measurements were used for monitoring functional changes in the diarrheic colon specimens. In parallel, tight junction protein expression was analyzed by Western blot and confocal laser-scanning microscopy, and signaling pathway analysis was performed using RNA sequencing and bioinformatics. Results: Epithelial resistance was decreased, indicating an epithelial leak flux diarrheal mechanism with a molecular correlate of decreased claudin-1 expression, while induction of active anion secretion and impairment of active sodium absorption via the epithelial sodium channel, ENaC, were not detected. The pathway analysis revealed activation of barrier-affecting cytokines TNF-α, IFN-γ, IL-1β and IL-4. Conclusions: Barrier dysfunction as a result of epithelial tight junction changes plays a role in IBS-D as a pathomechanism inducing a leak flux type of diarrhea.
Modeling RET-Rearranged Non-Small Cell Lung Cancer (NSCLC): Generation of Lung Progenitor Cells (LPCs) from Patient-Derived Induced Pluripotent Stem Cells (iPSCs)
Authors: Marcoux Paul , Hwang Jin Wook , Desterke Christophe , Imeri Jusuf , Bennaceur-Griscelli Annelise , Turhan Ali G.
Published: December 2023

REarranged during Transfection (RET) oncogenic rearrangements can occur in 1–2% of lung adenocarcinomas. While RET-driven NSCLC models have been developed using various approaches, no model based on patient-derived induced pluripotent stem cells (iPSCs) has yet been described. Patient-derived iPSCs hold great promise for disease modeling and drug screening. However, generating iPSCs with specific oncogenic drivers, like RET rearrangements, presents challenges due to reprogramming efficiency and genotypic variability within tumors. To address this issue, we aimed to generate lung progenitor cells (LPCs) from patient-derived iPSCs carrying the mutation RETC634Y, commonly associated with medullary thyroid carcinoma. Additionally, we established a RETC634Y knock-in iPSC model to validate the effect of this oncogenic mutation during LPC differentiation. We successfully generated LPCs from RETC634Y iPSCs using a 16-day protocol and detected an overexpression of cancer-associated markers as compared to control iPSCs. Transcriptomic analysis revealed a distinct signature of NSCLC tumor repression, suggesting a lung multilineage lung dedifferentiation, along with an upregulated signature associated with RETC634Y mutation, potentially linked to poor NSCLC prognosis. These findings were validated using the RETC634Y knock-in iPSC model, highlighting key cancerous targets such as PROM2 and C1QTNF6, known to be associated with poor prognostic outcomes. Furthermore, the LPCs derived from RETC634Y iPSCs exhibited a positive response to the RET inhibitor pralsetinib, evidenced by the downregulation of the cancer markers. This study provides a novel patient-derived off-the-shelf iPSC model of RET-driven NSCLC, paving the way for exploring the molecular mechanisms involved in RET-driven NSCLC to study disease progression and to uncover potential therapeutic targets.
Nanomaterials for Potential Detection and Remediation: A Review of Their Analytical and Environmental Applications
Authors: Salazar Sandoval Sebastián , Bruna Tamara , Maldonado-Bravo Francisca , Jara Paul , Caro Nelson , Rojas-Romo Carlos , González-Casanova Jorge , Gómez Diana Rojas , Yutronic Nicolás , Urzúa Marcela , Rodríguez-San Pedro Annia
Published: December 2023

The rapid increase in industrialization and human population is leading to critical levels of environmental pollutants, such as agrochemicals or heavy metals, which affect the preservation and integrity of ecosystems, the accessibility to drinking water sources, and the quality of the air. As such, remediation of these issues demands strategies for implementing and designing novel technologies. In that regard, nanomaterials have unique physicochemical properties that make them desirable candidates for the detection and remediation of environmental pollutants. The scope of this review is to provide an analysis of the available nanomaterials that are being used as an approach to detect and remediate hazardous residues, comprising systems such as noble metals, biosensors, cyclodextrin-based polymers, and graphene oxide nanocomposites, to name a few. Furthermore, this work discusses said nanomaterials in terms of their effectiveness, sustainability, and selectivity as a guideline for researchers wishing to indulge in this relevant study area.
Analysis of Surface Roughness during Surface Polishing of ITO Thin Film Using Acoustic Emission Sensor Monitoring
Authors: Kim Hyo-Jeong , Lee Hee-Hwan , Lee Seoung-Hwan
Published: December 2023

This study investigates the intricate process of surface polishing for ITO-coated Pyrex glass utilizing magnetic abrasive polishing (MAP) while employing acoustic emission (AE) sensors for real-time defect monitoring. MAP, known for its versatility in achieving nanoscale thickness processing and uniform surfaces, has been widely used in various materials. However, the complexity of the process, influenced by multiple variables like cutting conditions, material properties, and environmental factors, poses challenges to maintaining high surface quality. To address this, a sensor monitoring system, specifically one that uses AE sensors, was integrated into the MAP process to detect and confirm defects, providing real-time insights into machining conditions and outcomes. AE sensors excel in identifying material deterioration, microcrack formation, and wear, even in cases of minor damage. Leveraging AE sensor data, this study aims to minimize surface defects in ITO thin films during MAP while optimizing surface roughness. The investigation involves theoretical validation, magnetic density simulations, and force sensor pressure measurements to identify factors influencing surface roughness. ANOVA analysis is employed to determine optimal processing conditions. Additionally, this study compares the identified optimal roughness conditions with those predicted by AE sensor parameters, aiming to establish a correlation between predicted and achieved surface quality. The integration of AE sensor monitoring within the MAP process offers a promising avenue for enhancing surface quality by effectively identifying and addressing defects in real time. This comprehensive analysis contributes to advancing the understanding of surface polishing methodologies for ITO-coated Pyrex glass, paving the way for improved precision and quality in thin-film surface processes.
Nanostructure Engineering of Alloy-Based Anode Materials with Different Dimensions for Sodium/Potassium Storage
Authors: Cheng Xiaolong , Li Dongjun , Jiang Yu , Huang Fangzhi , Li Shikuo
Published: December 2023

Sodium/potassium-ion batteries have drawn intensive investigation interest from researchers owing to their abundant element resources and significant cost advantages. Anode materials based on alloy reaction mechanisms have the prominent merits of a suitable reaction potential and high theoretical specific capacity and energy density. However, very large volumetric stresses and volume changes during the charge/discharge process and the resulting electrode structural cracking, deactivation and capacity fading seriously hinder their development. To date, a series of modification strategies have been proposed to tackle these challenges and achieve good electrochemical performance. Herein, we review the recent advances in the structural engineering of alloy-type anodes for sodium/potassium storage, mainly including phosphorus, tin, antimony, bismuth and related alloy materials, from the perspective of dimensional structure. Furthermore, some future research directions and unresolved issues are presented for the investigation of alloy-based anode materials. It is hoped that this review can serve as a guide for the future development and practical application of sodium/potassium-ion batteries.
Heterogeneous Substrates Modify Non-Classical Nucleation Pathways: Reanalysis of Kinetic Data from the Electrodeposition of Mercury on Platinum Using Hierarchy of Sigmoid Growth Models
Authors: Kleshtanova Viktoria , Ivanov Vassil V. , Hodzhaoglu Feyzim , Prieto Jose Emilio , Tonchev Vesselin
Published: December 2023

Using a hierarchy of three sigmoid growth models with increasing complexity, i.e., number of parameters, we reanalyzed kinetic data for heterogeneous nucleation—the number of nuclei N(t) vs. time t—from archetypical experiments on the electrodeposition of mercury on platinum by I. Markov and E. Stoycheva, to obtain two scales: Nmax and τ. The universal character of the studied phenomenon was revealed when replotting the original data as α ≡ N(t)/Nmax vs. t/τ. Yet the simplest model, the recently introduced α21 model which is aimed to describe diffusion-limited growth in 2D, α21 = tanh2(2t/τ21), fits all datasets with an R2 ≥ 0.989. This can be rationalized by attracting the non-classical notion of two-step nucleation—the nuclei form in a metastable phase which, in this case, grows on the electrode surface. Beyond the universality, we find the dependence of the two obtained scales on the overvoltage, which is increased systematically from 83 to 88 mV to generate the six N(t) datasets for each of the two electrode types—planar and hemispherical. Surprisingly, for one of them, the planar electrode, there is a discontinuity in the dependence—an almost horizontal jump from 85 to 86 mV, while for the hemispherical electrode, τ decreases smoothly.