bluuebunny/crossref_metadata_2025 huggingface dataset:
The Effects of Onychectomy (Declawing) on Forearm and Leg Myology in a Kinkajou (Potos flavus)
Authors: Martens Lara L. , Brown Reece A. , Faillace Ana Carolina Lourenço , Berger Arin , Smith Rachel L. J. , Bertok Kathryn , Humphries Lauren , Lassiter Angela , Hartstone-Rose Adam
Published: September 2024

Recently, onychectomy, the “declaw” surgery in which all or part of the distal phalanges are removed, has been shown to have significant effects on the forearm muscles of felids. While this surgery should clearly affect the limb muscles (especially those that insert on the removed or modified bone), these effects have not been studied beyond felids or in the hindlimb. To that end, we herein evaluated the muscle architecture of a kinkajou (Potos flavus) that was declawed on all four of its limbs and compared its anatomy to that of intact specimens and the felid findings. As expected, some of the declawed kinkajou’s muscles were substantially different from those of the intact specimens, and as was seen in felids, its digital muscles appear to have been weaker. However, unlike in the felids, the declawed kinkajou had relatively larger forearm muscles. Also, contrary to expectation, the leg muscles of the declawed kinkajou were not substantially different, perhaps reflecting important differences in limb use. Future analyses should examine this anatomy in other declawed kinkajou specimens and also look at the effects of this surgery in other taxa, for instance, non-arboreal relatives of the kinkajou as well as other arboreal taxa.
Sturnidae sensu lato Mitogenomics: Novel Insights into Codon Aversion, Selection, and Phylogeny
Authors: Han Shiyun , Ding Hengwu , Peng Hui , Dai Chenwei , Zhang Sijia , Yang Jianke , Gao Jinming , Kan Xianzhao
Published: September 2024

The Sturnidae family comprises 123 recognized species in 35 genera. The taxa Mimidae and Buphagidae were formerly treated as subfamilies within Sturnidae. The phylogenetic relationships among the Sturnidae and related taxa (Sturnidae sensu lato) remain unresolved due to high rates of morphological change and concomitant morphological homoplasy. This study presents five new mitogenomes of Sturnidae sensu lato and comprehensive mitogenomic analyses. The investigated mitogenomes exhibit an identical gene composition of 37 genes—including 13 protein-coding genes (PCGs), 2 rRNA genes, and 22 tRNA genes—and one control region (CR). The most important finding of this study is drawn from CAM analyses. The surprisingly unique motifs for each species provide a new direction for the molecular species identification of avian. Furthermore, the pervasiveness of the natural selection of PCGs is found in all examined species when analyzing their nucleotide composition and codon usage. We also determine the structures of mt-tRNA, mt-rRNA, and CR structures of Sturnidae sensu lato. Lastly, our phylogenetic analyses not only well support the monophyly of Sturnidae, Mimidae, and Buphagidae, but also define nine stable subclades. Taken together, our findings will enable the further elucidation of the evolutionary relationships within Sturnidae sensu lato.
Nutrient Digestive Bypass: Determinants and Associations with Stool Quality in Cats and Dogs
Authors: Jackson Matthew I. , Wernimont Susan M. , Carnagey Kristen , Jewell Dennis E.
Published: September 2024

The effect of digestive bypass macronutrients and age on stool quality (moisture and firmness) in dogs and cats is not well understood. Data were analyzed from digestibility tests (n = 2020, 361 dogs and 536 cats) including dry and wet product types. Both food and feces were measured for moisture and nutrients according to standard protocols; stool firmness was graded. Linear mixed modeling was used to evaluate the associations between nutrient bypass, age and stool quality. Bypass protein increased stool moisture (dog, cat p < 0.0001) and decreased firmness (dog p = 0.01, cat p < 0.0001), while bypass fiber decreased stool moisture and increased firmness (dog, cat p < 0.0001 for both). Both species manifested a negative quadratic effect of advanced age on stool firmness (dog p < 0.0001 and cat p = 0.02). However, the association of advanced age (quadratic effect) with metabolizable energy required to maintain body weight was different between species; dogs had a positive association (p = 0.028), while it was negative for cats (p < 0.0001). Taken together, these data may aid in the development of food formulations for companion animals, which can better meet changing nutritional needs across life stages.
Location, Age, and Antibodies Predict Avian Influenza Virus Shedding in Ring-Billed and Franklin’s Gulls in Minnesota
Authors: Michalska-Smith Matthew , Clements Eva , Rasmussen Elizabeth , Culhane Marie R. , Craft Meggan E.
Published: September 2024

Influenza A virus (IAV) is a multi-host pathogen maintained in water birds and capable of spillover into humans, wildlife, and livestock. Prior research has focused on dabbling ducks as a known IAV reservoir species, yet our understanding of influenza dynamics in other water birds, including gulls, is lacking. Here, we quantify morphological and environmental drivers of serological (antibody detection by ELISA) and virological (viral RNA detection by PCR) prevalence in two gull species: ring-billed (Larus delawarensis) and Franklin’s (Leucophaeus pipixcan) gulls. Across 12 months and 10 locations, we tested over 1500 gulls for influenza viral RNA, and additionally tested antibody levels in nearly 1000 of these. We find substantial virus prevalence and a large, nonoverlapping seroprevalence, with significant differences across age and species classifications. The body condition index had minimal explanatory power to predict (sero)positivity, and the effect of the surrounding environment was idiosyncratic. Our results hint at a nontrivial relationship between virus and seropositivity, highlighting serological surveillance as a valuable counterpoint to PCR. By providing indication of both past infections and susceptibility to future infections, serosurveillance can help inform the distribution of limited resources to maximize surveillance effectiveness for a disease of high human, wildlife, and livestock concern.
A Snapshot of the Global Trade of South African Native Vertebrate Species Not Listed on CITES
Authors: Shivambu Ndivhuwo , Shivambu Tinyiko Cavin , Nelufule Takalani , Moshobane Moleseng Claude , Seoraj-Pillai Nimmi , Nangammbi Tshifhiwa Constance
Published: September 2024

The Convention on International Trade in Endangered Species of Wild Fauna and Flora (CITES) aims to prevent the overexploitation of species by controlling their trade. However, there is currently no international regulatory framework to protect the trade of non-CITES species. We examined the LEMIS database, online trade, and scientific literature with the aim of identifying and compiling a list of South African native species traded as pets and wildlife products. We found that there are 223 non-CITES species traded as wildlife products and 95 species traded as pets. Mammals and birds were the most traded taxa for wildlife products, while reptiles and amphibians were mostly traded as pets. At the least, species traded as wildlife products and pets are currently not facing extinction, as most are categorized as Least Concern. However, some endemic species have an unknown population size, with Sclerophrys pantherina and Neamblysomus gunningi being Endangered. The international pet trade involves 10 countries, with the USA, the Czech Republic, and the UK being the largest importers. The trade of species as wildlife products involves 20 countries, with the USA being the major importer. This study emphasizes the necessity of strict regulations and international cooperation to control the wildlife trade effectively.
M2Former: Multiscale Patch Selection for Fine-Grained Visual Recognition
Authors: Moon Jiyong , Park Seongsik
Published: September 2024

Recently, Vision Transformers (ViTs) have been actively applied to fine-grained visual recognition (FGVR). ViT can effectively model the interdependencies between patch-divided object regions through an inherent self-attention mechanism. In addition, patch selection is used with ViT to remove redundant patch information and highlight the most discriminative object patches. However, existing ViT-based FGVR models are limited to single-scale processing, and their fixed receptive fields hinder representational richness and exacerbate vulnerability to scale variability. Therefore, we propose MultiScale Patch Selection (MSPS) to improve the multiscale capabilities of existing ViT-based models. Specifically, MSPS selects salient patches of different scales at different stages of a MultiScale Vision Transformer (MS-ViT). In addition, we introduce Class Token Transfer (CTT) and MultiScale Cross-Attention (MSCA) to model cross-scale interactions between selected multiscale patches and fully reflect them in model decisions. Compared with previous Single-Scale Patch Selection (SSPS), our proposed MSPS encourages richer object representations based on feature hierarchy and consistently improves performance from small-sized to large-sized objects. As a result, we propose M2Former, which outperforms CNN-/ViT-based models on several widely used FGVR benchmarks.
Neural Network System for Predicting Anomalous Data in Applied Sensor Systems
Authors: Vladov Serhii , Vysotska Victoria , Sokurenko Valerii , Muzychuk Oleksandr , Nazarkevych Mariia , Lytvyn Vasyl
Published: September 2024

This article advances the research on the intelligent monitoring and control of helicopter turboshaft engines in onboard conditions. The proposed neural network system for anomaly prediction functions as a module within the helicopter turboshaft engine monitoring and control expert system. A SARIMAX-based preprocessor model was developed to determine autocorrelation and partial autocorrelation in training data, accounting for dynamic changes and external factors, achieving a prediction accuracy of up to 97.9%. A modified LSTM-based predictor model with Dropout and Dense layers predicted sensor data, with a tested error margin of 0.218% for predicting the TV3-117 aircraft engine gas temperature values before the compressor turbine during one minute of helicopter flight. A reconstructor model restored missing time series values and replaced outliers with synthetic values, achieving up to 98.73% accuracy. An anomaly detector model using the concept of dissonance successfully identified two anomalies: a sensor malfunction and a sharp temperature drop within two minutes of sensor activity, with type I and II errors below 1.12 and 1.01% and a detection time under 1.611 s. The system’s AUC-ROC value of 0.818 confirms its strong ability to differentiate between normal and anomalous data, ensuring reliable and accurate anomaly detection. The limitations involve the dependency on the quality of data from onboard sensors, affected by malfunctions or noise, with the LSTM network’s accuracy (up to 97.9%) varying with helicopter conditions, and the model’s high computational demand potentially limiting real-time use in resource-constrained environments.
Digital Forensics Readiness in Big Data Networks: A Novel Framework and Incident Response Script for Linux–Hadoop Environments
Authors: Mpungu Cephas , George Carlisle , Mapp Glenford
Published: September 2024

The surge in big data and analytics has catalysed the proliferation of cybercrime, largely driven by organisations’ intensified focus on gathering and processing personal data for profit while often overlooking security considerations. Hadoop and its derivatives are prominent platforms for managing big data; however, investigating security incidents within Hadoop environments poses intricate challenges due to scale, distribution, data diversity, replication, component complexity, and dynamicity. This paper proposes a big data digital forensics readiness framework and an incident response script for Linux–Hadoop environments, streamlining preliminary investigations. The framework offers a novel approach to digital forensics in the domains of big data and Hadoop environments. A prototype of the incident response script for Linux–Hadoop environments was developed and evaluated through comprehensive functionality and usability testing. The results demonstrated robust performance and efficacy.
An Event Horizon ‘Firewall’ Undergoing Cosmological Expansion
Authors: Henriksen Richard N. , Emslie A. Gordon
Published: September 2024

We embed an object with a singular horizon structure, reminiscent of (but fundamentally different from, except in a limiting case) a black hole event horizon, in an expanding, spherically symmetric, homogeneous, Universe that has a positive cosmological constant. Conformal representation is discussed. There is a temperature/pressure singularity and a corresponding scalar curvature singularity at the horizon. The expanding singular horizon ultimately bounds the entire spacetime manifold. It is is preceded by an expanding light front, which separates the spacetime affected by the singularity from that which is not yet affected. An appropriately located observer in front of the light front can have a Hubble–Lemaître constant that is consistent with that currently observed.
Factors Influencing Radon Variability and Measurement Protocol Optimization in Romanian Educational Buildings Using Integrated and Continuous Measurements
Authors: Dobrei Gabriel-Cristian , Moldovan Mircea-Claudiu , Dicu Tiberius , Florică Ștefan , Lupulescu Alexandru-Iulian , Țenter Ancuța-Cristina , Cucoș Alexandra
Published: September 2024

Due to the higher susceptibility of children to ionizing radiation, it is imperative to evaluate the radon activity concentration (RAC) in educational buildings, conduct additional investigations to identify radon entry routes, and implement remedial measures to minimize exposure to this radioactive gas. In Romania, educational buildings are a category of public buildings where it is mandatory to perform RAC measurements. The present study examines data obtained from 41 Romanian educational buildings, where initial and additional radon investigations were performed. The first objective was to identify the factors influencing the variability of the RAC inside the buildings. The second objective was to emphasize the importance of short-term (a few days), continuous measurements in identifying buildings with RAC exceeding the reference level. High RAC values were associated with the classrooms located on the ground floor of the building compared to the administrative ones. The multiple linear regression led to a coefficient of determination of 0.11, the relative humidity and the amount of precipitation being the main variables with a significant impact, kept in the model, the lack of a significant association between the indoor RAC and the radon potential in the soil being obtained. Comparison of the radon long-term integrated measurements with continuous, short-term, led to the suggestion of three different scenarios for the measurement work protocol. By following the suggested modifications, it is possible to accelerate the procedure in situations where the time needed to plan renovations and radon remedial measures is shorter than the time needed to conduct integrated measurements.
Emerging and Current Biologics for the Treatment of Intracranial Aneurysms
Authors: Tenhoeve Samuel A. , Owens Monica-Rae , Rezk Rogina , Hanna Abanob G. , Lucke-Wold Brandon
Published: September 2024

The integration of biologics in endovascularly treated intracranial aneurysms is a significant area of focus in an evolving field. By presenting the clinical relevance, pathogenesis, management (historical and current), and emerging biologics themselves, this work provides a broad overview of the current landscape of the biologics under current investigation. Growth factors, cytokines, and biologic-coated coils are compared and described as modalities to increase healing, aneurysm occlusion, and long-term recovery. These emerging biologics may increase the efficacy and durability of less invasive endovascular methods and potentially change standard practice with continued exploration.
Antibacterial, Antifungal, and Cytotoxic Effects of Endophytic Streptomyces Species Isolated from the Himalayan Regions of Nepal and Their Metabolite Study
Authors: Yadav Ram Prabodh , Huo Chen , Budhathoki Rabin , Budthapa Padamlal , Bhattarai Bibek Raj , Rana Monika , Kim Ki Hyun , Parajuli Niranjan
Published: September 2024

Background/Objectives: Recently, antimicrobial-resistant pathogens and cancers have emerged as serious global health problems, highlighting the immediate need for novel therapeutics. Consequently, we aimed to isolate and characterize endophytic Streptomyces strains from the rhizospheres of the Himalayan region of Nepal and identify specialized metabolites with antibacterial, antifungal, and cytotoxic potential. Methods: To isolate Streptomyces sp., we collected two soil samples and cultured them on an ISP4 medium after pretreatment. We isolated and identified the strains PY108 and PY109 using a combination of morphological observations and 16S rRNA gene sequencing. Results: The BLAST results showed that PY108 and PY109 resembled Streptomyces hundungensis PSB170 and Streptomyces sp. Ed-065 with 99.28% and 99.36% nucleotide similarity, respectively. Antibacterial assays of ethyl acetate (EA) extracts from both isolates PY108 and PY109 in a tryptic soy broth (TSB) medium were conducted against four pathogenic bacteria. They showed significant antibacterial potential against Staphylococcus aureus and Klebsiella pneumoniae. Similarly, these extracts exhibited moderate antifungal activities against Saccharomyces cerevisiae and Aspergillus niger. Cytotoxicity assays on cervical cancer cells (HeLa) and breast cancer cells (MCF-7) revealed significant potential for both extracts. LC-MS/MS profiling of the EA extracts identified 27 specialized metabolites, including diketopiperazine derivatives, aureolic acid derivatives such as chromomycin A, and lipopeptide derivatives. In comparison, GC-MS analysis detected 34 metabolites, including actinomycin D and γ-sitosterol. Furthermore, a global natural product social molecular networking (GNPS)-based molecular networking analysis dereplicated 24 metabolites in both extracts. Conclusions: These findings underscore the potential of endophytic Streptomyces sp. PY108 and PY109 to develop new therapeutics in the future.
Neuronal Mechanisms of Reading Informational Texts in People with Different Levels of Mental Resilience
Authors: Chojak Małgorzata , Gawron Anna , Czechowska-Bieluga Marta , Różański Andrzej , Sarzyńska-Mazurek Ewa , Stachyra-Sokulska Anna
Published: September 2024

The aim of this study was to verify whether the level of mental resilience would differentiate reading comprehension performance when using different information carriers. More than 150 people filled out a test regarding the level of resilience. They then participated in a survey using fNIRS. Their task was to read a one-page informational text and answer several questions. The results showed no differences in correct answers between groups of people with different levels of resilience. In the groups of people with high and low levels of resilience, the number of correct answers was not differentiated by the type of carrier. Among those with moderate levels of resilience, better results were obtained by those who read text printed on paper. Analyses of neuronal mechanisms showed that the type of carrier differentiated brain activity in each group. Obtaining the same number of correct answers in the test was the result of different neuronal mechanisms activated in those who used a computer and those who read a printed text.
Pain Neuroscience Education and Neuroimaging—A Narrative Review
Authors: Corbo Daniele
Published: September 2024

Background: Musculoskeletal pain is a leading cause of medical visits, posing significant challenges both socially and economically, encouraging the scientific community to continue researching and exploring the most effective methods to address the problem. An alternative way to deal with chronic pain is pain neuroscience education (PNE), a lesson plan that addresses the neurobiology, neurophysiology, and nervous system processing of pain. This method takes the place of the conventional one, which connected pain to tissue damage or nociception. Results: As a result, patients are taught that pain is often not a reliable measure of the health of the tissues but rather the outcome of the nervous system interpreting the injury in conjunction with additional psychosocial variables. In addition to finding research that examine, using neuroimaging, whether the administration of PNE has detectable effects at the level of the central nervous system, this narrative review seeks to clarify what PNE is, how it is administered, and if it is an effective treatment for musculoskeletal pain. Conclusions: Based on the findings, it appears that PNE is more therapeutically beneficial when combined with therapeutic exercise, when done one-on-one, and during lengthy, frequent sessions. Lastly, even though PNE has no effect on the morphological properties of the gray matter, it appears to cause decreased activation of the regions linked to pain.
Estimating the Prevalence of Cognitive Impairment and Its Associated Factors in Albania: A Nationwide Cross-Sectional Study
Authors: Hoxha Malvina , Galgani Simonetta , Kruja Jera , Alimehmeti Ilir , Rapo Viktor , Çipi Frenki , Tricarico Domenico , Zappacosta Bruno
Published: September 2024

Background/Objectives: Cognitive impairment is an intermediate state between normal aging and dementia, and its detection in the early stages is essential to prevent dementia, an incurable pathology. The aim of this study is to screen and estimate the prevalence of cognitive impairment, including dementia, and its correlated factors in a community-based sample of the Albanian population over 50 years old. Methods: We carried out a door-to-door neuropsychological screening of Albanian residents older than 50 years from November 2023 to June 2024 in 12 Albanian districts. Participants completed the Early Dementia Questionnaire (EDQ) and the Mini Mental State Examination (MMSE). Results: The overall estimating prevalence of cognitive impairment and early dementia among the Albanian population over 50 years old was 14.04% using the MMSE, with 2.31% for MMSE ≤18 (serious cognitive impairment), 5.51% for MMSE 19–22 (mild cognitive impairment (MCI)), and 6.22 for MMSE 23–24 (suspected cognitive impairment or dementia),respectively. The prevalence of early dementia using the EDQ was significantly higher (53.99%).The number of male participants with MMSE scores of 23–24 (suspected cognitive impairment or early dementia) was 2.5 times higher with respect to female participants. Smoking and alcohol consumption decreased the MMSE scores. The number of participants with normal cognitive function (MMSE scores 25–30) was lower among participants with hypertension, diabetes, hyperlipidemia, and cerebral ischemia. Conclusions: A diagnostic evaluation, including a clinical examination, neuroimaging, and laboratory studies, is further required for a diagnosis. Despite limitations, the data provided in this study are the only ones reported for a large community-based sample of the older adult Albanian population, which can help health care providers to diagnose cognitive impairment.
Advances in Neuroinflammation
Authors: Wang Junhui , Sun Jing , Wang Hongxing
Published: September 2024

Recent research in neuroscience has shown significant advancements in relation to neuroinflammation, especially its role in neurological diseases, including neurodegenerative diseases [...]
The Role of Brain Plasticity in Neuromuscular Disorders: Current Knowledge and Future Prospects
Authors: Alonge Paolo , Gadaleta Giulio , Urbano Guido , Lupica Antonino , Di Stefano Vincenzo , Brighina Filippo , Torrente Angelo
Published: September 2024

Background/Objectives: Increasing evidence shows an involvement of brain plasticity mechanisms in both motor and central manifestations of neuromuscular disorders (NMDs). These mechanisms could be specifically addressed with neuromodulation or rehabilitation protocols. The aim of this scoping review is to summarise the evidence on plasticity mechanisms’ involvement in NMDs to encourage future research. Methods: A scoping review was conducted searching the PubMed and Scopus electronic databases. We selected papers addressing brain plasticity and central nervous system (CNS) studies through non-invasive brain stimulation techniques in myopathies, muscular dystrophies, myositis and spinal muscular atrophy. Results: A total of 49 papers were selected for full-text examination. Regardless of the variety of pathogenetic and clinical characteristics of NMDs, studies show widespread changes in intracortical inhibition mechanisms, as well as disruptions in glutamatergic and GABAergic transmission, resulting in altered brain plasticity. Therapeutic interventions with neurostimulation techniques, despite being conducted only anecdotally or on small samples, show promising results; Conclusions: despite challenges posed by the rarity and heterogeneity of NMDs, recent evidence suggests that synaptic plasticity may play a role in the pathogenesis of various muscular diseases, affecting not only central symptoms but also strength and fatigue. Key questions remain unanswered about the role of plasticity and its potential as a therapeutic target. As disease-modifying therapies advance, understanding CNS involvement in NMDs could lead to more tailored treatments.
On-Site Measuring Robot Technology for Post-Construction Quality Assessment of Building Projects
Authors: Wu Hangzi , Ma Minglei , Yang Yan , Han Lifang , Wu Siyuan
Published: September 2024

Post-construction quality assessment of building projects involves inspecting and verifying that completed construction works meet the specified standards. This process is traditionally conducted through manual methods, which can be inefficient and time-consuming. Existing measurement robots, typically integrating a robotic platform with 3D laser scanners, face challenges such as high storage demands, reliance on specialized post-processing software, and substantial costs. Additionally, robots with multiple sensors may face limitations in handling diverse measurement items. To address these issues, this article introduces a cost-effective and fully automated on-site measuring robot. A systematic approach was employed, including robot design, measurement algorithm development, validation experiments, and engineering applications. Firstly, a cost-effective hardware was designed, reducing expenses by 30% compared to commercial 3D laser scanners. Thereafter, the algorithm was developed by processing effective point cloud data to measure dimensions, wall evenness, alignments, floor heights, and corner angles, achieving a 90% reduction in data storage requirements. Subsequently, validation experiments were conducted, which verified the measurement accuracy of the developed robot. Furthermore, the robot was applied in two building projects, demonstrating a 40% improvement in efficiency over manual measurements and a minimum 50% reduction in labor costs. This investigation shows that the developed on-site measuring robot offers a practical and automated solution for post-construction quality assessment in building projects.
Germline Polymorphisms Associated with Overall Survival in Lung Adenocarcinoma: Genome-Wide Analysis
Authors: Minnai Francesca , Noci Sara , Esposito Martina , Schneider Marc A. , Kobinger Sonja , Eichhorn Martin , Winter Hauke , Hoffmann Hans , Kriegsmann Mark , Incarbone Matteo A. , Mattioni Giovanni , Tosi Davide , Muley Thomas , Dragani Tommaso A. , Colombo Francesca
Published: September 2024

Background/Objectives: Lung cancer remains a global health concern, with substantial variation in patient survival. Despite advances in detection and treatment, the genetic basis for the divergent outcomes is not understood. We investigated germline polymorphisms that modulate overall survival in 1464 surgically resected lung adenocarcinoma patients. Methods: A multivariable Cox proportional hazard model was used to assess the association of more than seven million polymorphisms with overall survival at the 60-month follow-up, considering age, sex, pathological stage, decade of surgery and principal components as covariates. Genes in which variants were identified were studied in silico to investigate functional roles. Results: Six germline variants passed the genome-wide significance threshold. These single nucleotide polymorphisms were mapped to non-coding (intronic) regions on chromosomes 2, 3, and 5. The minor alleles of rs13000315, rs151212827, and rs190923216 (chr. 2, 3 and 5, respectively) were found to be independent negative prognostic factors. All six variants have been reported to regulate the expression of nine genes, seven of which are protein-coding, in different tissues. Survival-associated variants on chromosomes 2 and 3 were already reported to regulate the expression of NT5DC2 and NAGK, with high expression associated with the minor alleles. High NT5DC2 and NAGK expression in lung adenocarcinoma tissue was already shown to correlate with poor overall survival. Conclusions: This study highlights a potential regulatory role of the identified polymorphisms in influencing outcome and suggests a mechanistic link between these variants, gene expression regulation, and lung adenocarcinoma prognosis. Validation and functional studies are warranted to elucidate the mechanisms underlying these associations.
Unravelling the Complexity of HNSCC Using Single-Cell Transcriptomics
Authors: Conde-Lopez Cristina , Marripati Divyasree , Elkabets Moshe , Hess Jochen , Kurth Ina
Published: September 2024

Background/Objectives: Head and neck squamous cell carcinoma (HNSCC) is a highly heterogeneous and the most common form of head and neck cancer, posing significant challenges for disease management. The objective of this review is to assess the utility of single-cell RNA sequencing (scRNAseq) in addressing these challenges by enabling a detailed characterization of the tumor microenvironment (TME) at the cellular level. Methods: This review compiles and analyzes current strategies that utilize scRNAseq and other single-cell technologies in HNSCC research. Results: For HNSCC etiology, scRNAseq allows for the construction of cellular atlases, characterization of different cell types, and investigation of genes and processes involved in cancer initiation, development, and progression within the TME. In terms of HNSCC diagnosis and prognosis, the resolution offered by scRNAseq enables the identification of cell type-specific signatures, enhancing prognostic models and disease stratifiers for patient outcome assessments. Regarding HNSCC treatment, scRNAseq provides insights into cellular responses to various treatments, including radiotherapy, chemotherapy, and immunotherapy, contributing to a better understanding of treatment efficacy and patient outcomes. Conclusions: This review highlights the contributions of scRNAseq to HNSCC research, addressing its cellular and biological complexity, and emphasizes its potential for advancing research and clinical practice in other cancer types.
Novel Targeted Agents in Advanced and Recurrent Low-Grade Serous Ovarian Cancer: A Silver Lining in the Therapy of a Chemoresistant Disease?
Authors: Onoprienko Arina , Bartl Thomas , Grimm Christoph , Concin Nicole , Polterauer Stephan
Published: September 2024

Low-grade serous ovarian carcinoma (LGSOC) is a rare subtype of epithelial ovarian cancer, characterized by a unique molecular background and specific clinical behavior. A growing body of molecular data underscores LGSOC as a distinct disease entity; however, clinical evidence on the optimal treatment regimens for LGSOC remains limited due to the low incidence of the disease. Consequently, treatment recommendations for LGSOC are still often derived from findings on the more common high-grade serous ovarian carcinoma (HGSOC) and typically focus on radical cytoreductive surgery and platinum-based chemotherapy. Since LGSOCs typically exhibit only limited responsiveness to platinum-based chemotherapy, the clinical management of advanced and recurrent LGSOCs remains a significant therapeutic challenge and often results in limited treatment options and suboptimal outcomes. Recent advances in molecular profiling and the identification of new, promising targets, such as the mitogen-activated protein kinase (MAPK) pathway, offer hope for improving both the prognosis and health-related quality of life in affected patients. Given the high unmet clinical need to establish new therapeutic standards beyond cytotoxic chemotherapy, this review aims to summarize the most promising molecular targets and emerging targeted agents.
FBXO11 Mediates Ubiquitination of ZEB1 and Modulates Epithelial-to-Mesenchymal Transition in Lung Cancer Cells
Authors: Zhao Xinyue , Han Zhihui , Liu Ruiying , Li Zehao , Mei Ling , Jin Yue
Published: September 2024

Epithelial-to-mesenchymal transition (EMT) affects the invasion and migration of cancer cells. Here, we show that FBXO11 recognizes and promotes ubiquitin-mediated degradation of ZEB1. There is a strong association between FBXO11 and ZEB1 in non-small cell lung cancer (NSLC) in a clinical database. FBXO11 interacts with ZEB1, a core inducer of EMT. FBXO11 leads to increased ubiquitination and proteasomal degradation of ZEB1. Depletion of endogenous FBXO11 causes ZEB1 protein accumulation and EMT in A549 and H1299 cells, while overexpression of FBXO11 reduces ZEB1 protein abundance and cellular invasiveness. Importantly, the depletion of ZEB1 suppresses the increased migration and invasion of A549 and H1299 cells promoted by the depletion of FBXO11. The same results are shown in xenograft tumors. High FBXO11 expression is associated with a favorable prognosis in NSLC. Collectively, our study demonstrates that FBXO11 modulates EMT by mediating the stability of ZEB1 in lung cancer cells.
Prioritizing Radiation and Targeted Systemic Therapies in Patients with Resected Brain Metastases from Lung Cancer Primaries with Targetable Mutations: A Report from a Multi-Site Single Institution
Authors: Wuu Yen-Ruh , Kokabee Mostafa , Gui Bin , Lee Simon , Stone Jacob , Karten Jessie , D’Amico Randy S. , Vojnic Morana , Wernicke A. Gabriella
Published: September 2024

Background/Objectives: Brain metastases (BrMs) are a common complication of non-small cell lung cancer (NSCLC), present in up to 50% of patients. While the treatment of BrMs requires a multidisciplinary approach with surgery, radiotherapy (RT), and systemic therapy, the advances in molecular sequencing have improved outcomes in patients with targetable mutations. With a push towards the molecular characterization of cancers, we evaluated the outcomes by treatment modality at our institution with respect to prioritizing RT and targeted therapies. Methods: We identified the patients with NSCLC BrMs treated with surgical resection. The primary endpoints were in-brain freedom from progression (FFP) and overall survival (OS). The secondary endpoint included index lesion recurrence. The tumor molecular profiles were reviewed. The outcomes were evaluated by treatment modality: surgery followed by adjuvant RT and/or adjuvant systemic therapy. Results: In total, 155/272 (57%) patients who received adjuvant therapy with adequate follow-up were included in this analysis. The patients treated with combination therapy vs. monotherapy had a median FFP time of 10.72 months vs. 5.38 months, respectively (p = 0.072). The patients of Hispanic/Latino vs. non-Hispanic/Latino descent had a statistically significant worse OS of 12.75 months vs. 53.15 months, respectively (p = 0.015). The patients who received multimodality therapy had a trend towards a reduction in index lesion recurrences (χ2 test, p = 0.063) with a statistically significant improvement in the patients receiving immunotherapy (χ2 test, p = 0.0018). Conclusions: We found that systemic therapy combined with RT may have an increasing role in delaying the time to progression; however, there was no statistically significant relationship between OS and treatment modality.
Genetic Analysis of Biopsy Tissues from Colorectal Tumors in Patients with Ulcerative Colitis
Authors: Yamamoto Noriko , Urabe Yuji , Nakahara Hikaru , Nakamura Takeo , Shimizu Daisuke , Konishi Hirona , Ishibashi Kazuki , Ariyoshi Misa , Miyamoto Ryo , Mizuno Junichi , Takasago Takeshi , Ishikawa Akira , Tsuboi Akiyoshi , Tanaka Hidenori , Yamashita Ken , Hiyama Yuichi , Kishida Yoshihiro , Takigawa Hidehiko , Kuwai Toshio , Arihiro Koji , Shimamoto Fumio , Oka Shiro
Published: September 2024

Background/Objectives: Colorectal neoplasia developing from ulcerative colitis mucosa (CRNUC) can be divided into ulcerative colitis-associated neoplasia (UCAN) and non-UCAN; however, it is often difficult to distinguish UCAN from non-UCAN during a biopsy diagnosis. We investigated whether a genomic analysis could improve the diagnostic accuracy of UCAN using biopsy specimens. Methods: In step 1, 14 CRNUCs were used to examine whether the genomic landscape of biopsy and resection specimens matched. In step 2, we investigated the relationship between the genomic landscapes and the pathological diagnosis of 26 CRNUCs. The cancer genome was analyzed by deep sequencing using a custom panel of 27 genes found to be mutated in our previous CRNUC analysis. Results: In step 1, of the 27 candidate genes, 14 were mutated. The concordance rate of the pathogenic mutations in these 14 genes between the biopsy and resection specimens was 29% (4/14), while that of the pathogenic mutations in TP53 and KRAS was 79% (11/14). In step 2, the pathological diagnosis of biopsy specimens using only hematoxylin and eosin (HE) staining had a sensitivity of 33% and an accuracy of 38% for UCAN diagnosis. On the other hand, the combination of the HE pathology and p53 immunohistochemical staining had a sensitivity of 73% and an accuracy of 85% for UCAN diagnosis, while the combination of HE staining and a TP53 mutation had a sensitivity of 87% and an accuracy of 88% for UCAN diagnosis. Conclusions: An evaluation of TP53 mutations in biopsy specimens may be useful for diagnosing UCAN. However, further studies with larger sample sizes are required before this can be applied in clinical practice.
Xeroderma Pigmentosum Type C Primary Skin Fibroblasts Overexpress HGF and Promote Squamous Cell Carcinoma Invasion in the Absence of Genotoxic Stress
Authors: Al-qaraghuli Sahar , Gache Yannick , Goncalves-Maia Maria , Alcor Damien , Muzotte Elodie , Mahfouf Walid , Rezvani Hamid-Reza , Magnaldo Thierry
Published: September 2024

Xeroderma pigmentosum (XP) is a very rare recessive disease caused by the incapacity to resolve ultraviolet-induced DNA lesions through Nucleotide Excision Repair (NER). Most XP patients suffer from aggressive skin carcinoma and melanoma at a very early age (<8). Our previous results showed that primary XP fibroblasts isolated from healthy (non-photo-exposed) skin negatively impact the extracellular matrix and fail to activate the innate immune system. Here, we show for the first time that XP-C fibroblasts also play a major role in cancer cell invasion ex vivo and in vivo through the overexpression of Hepatocyte Growth Factor/Scatter Factor (HGF/SF) in the absence of genotoxic attacks. The use of inhibitors of the activation of the HGF/SF pathway counteracted the effects of XP fibroblasts on the growth of cancer cells, suggesting new perspectives in the care of XP patients.
Genotoxic and Anti-Migratory Effects of Camptothecin Combined with Celastrol or Resveratrol in Metastatic and Stem-like Cells of Colon Cancer
Authors: Moreira Helena , Szyjka Anna , Bęben Dorota , Siwiela Oliwia , Radajewska Anna , Stankiewicz Nadia , Grzesiak Małgorzata , Wiatrak Benita , Emhemmed Fathi , Muller Christian D. , Barg Ewa
Published: September 2024

Background: Colorectal cancer is one of the leading and most lethal neoplasms. Standard chemotherapy is ineffective, especially in metastatic cancer, and does not target cancer stem cells. A promising approach to improve cancer treatment is the combination therapy of standard cytostatic drugs with natural compounds. Several plant-derived compounds have been proven to possess anticancer properties, including the induction of apoptosis and inhibition of cancer invasion. This study was focused on investigating in vitro the combination of camptothecin (CPT) with celastrol (CEL) or resveratrol (RSV) as a potential strategy to target metastatic (LOVO) and stem-like (LOVO/DX) colon cancer cells. Methods: The genotoxic effects that drive cancer cells into death-inducing pathways and the ability to inhibit the migratory properties of cancer cells were evaluated. The γH2AX+ assay and Fast-Halo Assay (FHA) were used to evaluate genotoxic effects, the annexin-V apoptosis assay to rate the level of apoptosis, and the scratch test to assess antimigratory capacity. Results: The results showed that both combinations CPT-CEL and CPT-RSV improve general genotoxicity of CPT alone on metastatic cells and CSCs. However, the assessment of specific double-stranded breaks (DSBs) indicated a better efficacy of the CPT-CEL combination on LOVO cells and CPT-RSV in LOVO/DX cells. Interestingly, the combinations CPT-CEL and CPT-RSV did not improve the pro-apoptotic effect of CPT alone, with both LOVO and LOVO/DX cells suggesting activation of different cell death mechanisms. Furthermore, it was found that the combinations of CPT-CEL and CPT-RSV improve the inhibitory effect of camptothecin on cell migration. Conclusions: These findings suggest the potential utility of combining camptothecin with celastrol or resveratrol in the treatment of colon cancer, including more aggressive forms of the disease. So far, no studies evaluating the effects of combinations of these compounds have been published in the available medical databases.
IDH2 Inhibitors Gain a Wildcard Status in the Cancer Therapeutics Competition
Authors: Piva Roberto , Gharari Nariman , Labrador Maria , Mader Sylvie
Published: September 2024

The metabolic reprogramming characteristic of cancer cells, including the Warburg effect, has long been recognized as a hallmark of malignancy. This commentary explores three recent investigations focusing on the role of wild-type IDH2 in cancer and immune cell function. The first publication identifies wild-type IDH2 as a crucial factor in the survival of triple-negative breast cancer (TNBC) cells, with its inhibition leading to disrupted energy metabolism, reduced tumor growth, and enhanced apoptosis. The second analysis examines the role of IDH2 in CD8+ T cells, revealing that its inhibition promotes the differentiation of memory T cells, thereby enhancing the efficacy of cell-based immunotherapies like CAR T cells. A third investigation supports these findings, demonstrating that IDH2 inhibition in CAR T cells reduces exhaustion, enhances memory T cell formation, and improves anti-tumor efficacy. Collectively, these reports highlight wild-type IDH2 as a promising therapeutic target, with potential applications as a two-edged sword in both cancer treatment and immunotherapy. The development of specific wild-type IDH2 inhibitors could offer new avenues for therapy, particularly in tumors reliant on IDH2 activity as well as in enhancing the effectiveness of CAR T cell therapies.
Immune Checkpoints and Cellular Landscape of the Tumor Microenvironment in Non-Melanoma Skin Cancer (NMSC)
Authors: Mousa Ahmed M. , Enk Alexander H. , Hassel Jessica C. , Reschke Robin
Published: September 2024

Non-melanoma skin cancer (NMSC) is primarily categorized into basal cell carcinoma (BCC), the most prevalent form of skin cancer, and cutaneous squamous cell carcinoma (cSCC), the second most common type. Both BCC and cSCC represent a significant health burden, particularly in immunocompromised individuals and the elderly. The immune system plays a pivotal role in the development and progression of NMSC, making it a critical focus for therapeutic interventions. This review highlights key immunological targets in BCC and cSCC, with a focus on immune checkpoint molecules such as PD-1/PD-L1 and CTLA-4, which regulate T cell activity and contribute to immune evasion. This review also highlights anti-tumor immune cell subsets within the tumor microenvironment (TME), such as tumor-infiltrating lymphocytes (TILs) and dendritic cells. Additionally, it examines the immunosuppressive elements of the TME, including regulatory T cells (Tregs), myeloid-derived suppressor cells (MDSCs), tumor-associated macrophages (TAMs), and cancer-associated fibroblasts (CAFs), as well as their roles in NMSC progression and resistance to therapy. Emerging strategies targeting these immune elements, such as monoclonal antibodies, are also discussed for their potential to enhance anti-tumor immune responses and improve clinical outcomes. By elucidating the immunological landscape of BCC and cSCC and drawing comparisons to melanoma, this review highlights the transformative potential of immunotherapy in treating these malignancies.
Alternative Ways to Obtain Human Mesenchymal Stem Cells from Embryonic Stem Cells
Authors: Onyanov Nikita , Glazova Olga , Sakr Nawar , Krokunova Tatyana , Krupinova Julia , Volchkov Pavel
Published: September 2024

Differentiation approaches to obtain mesenchymal stem cells (MSCs) have gradually developed over the last few decades. The problem is that different protocols give different MSC types, making further research difficult. Here, we tried three different approaches to differentiate embryonic stem cells (ESCs) from early mesoderm to MSCs using serum-containing or xeno-free differentiation medium and observed differences in the cells’ morphology, doubling rate, ability to form colonies, surface marker analysis, and multilineage differentiation potential of the obtained cell lines. We concluded that the xeno-free medium best fits the criteria of MSCs’ morphology, growth kinetics, and surface marker characterization. In contrast, the serum-containing medium gives better potential for further MSC differentiation into osteogenic, chondrogenic, and adipogenic lineages.
Recent Progress of Non-Volatile Memory Devices Based on Two-Dimensional Materials
Authors: Pan Jiong , Wang Zeda , Zhao Bingchen , Yin Jiaju , Guo Pengwen , Yang Yi , Ren Tian-Ling
Published: September 2024

With the development of artificial intelligence and edge computing, the demand for high-performance non-volatile memory devices has been rapidly increasing. Two-dimensional materials have ultrathin bodies, ultra-flattened surfaces, and superior physics properties, and are promising to be used in non-volatile memory devices. Various kinds of advanced non-volatile memory devices with semiconductor, insulator, ferroelectric, magnetic, and phase-change two-dimensional materials have been investigated in recent years to promote performance enhancement and functionality extension. In this article, the recent advances in two-dimensional material-based non-volatile memory devices are reviewed. Performance criteria and strategies of high-performance two-dimensional non-volatile memory devices are analyzed. Two-dimensional non-volatile memory array structures and their applications in compute-in-memory architectures are discussed. Finally, a summary of this article and future outlooks of two-dimensional non-volatile memory device developments are given.