bluuebunny/crossref_metadata_2025 huggingface dataset:
Habitat suitability modeling of loggerhead sea turtles in the Central-Eastern Mediterranean Sea: a machine learning approach using satellite tracking data
Authors: Maglietta Rosalia , Caccioppoli Rocco , Piazzolla Daniele , Saccotelli Leonardo , Cherubini Carla , Scagnoli Elena , Piermattei Viviana , Marcelli Marco , De Lucia Giuseppe Andrea , Lecci Rita , Causio Salvatore , Dimauro Giovanni , De Franco Francesco , Scuro Matteo , Coppini Giovanni
Published: November 2024

Understanding how sea turtle species move through the environment and respond to environmental features is fundamental for sustainable ecosystem management and effective conservation. This study investigates the habitat suitability of the loggerhead sea turtle (Caretta caretta) in the Adriatic and Northern Ionian Seas (Central-Eastern Mediterranean) by developing and validating a multidisciplinary framework that leverages machine learning to investigate movement patterns collected by satellite tags Argos satellite tags. Satellite tracking data, enriched with sixteen environmental variables from the Copernicus Marine Service and EMODnet-bathymetry, were analyzed using Random Forest models, obtaining an accuracy of 80.9% when classifying presence versus pseudo-absence of loggerhead sea turtles. As main findings, sea bottom depth, surface chlorophyll (chl-a), and mixed layer depth (MLD) were identified as the most influential features in the habitat suitability of these specimens. Moreover, statistically significant differences, evaluated using t-test statistics, were found between coastal and pelagic locations, for the different seasons, in mixed layer depth, chl-a, 3D-clorophyll, salinity and phosphate. Although based on a limited sample of tagged animals, this study demonstrates that the distribution patterns of loggerhead sea turtles in Mediterranean coastal and pelagic areas are primarily influenced by sea water features linked to productivity and, consequently, to potential prey abundance. Additionally, this multidisciplinary framework presents a replicable approach that can be adapted for various species and regions.
A novel method for optimizing epilepsy detection features through multi-domain feature fusion and selection
Authors: Kong Guanqing , Ma Shuang , Zhao Wei , Wang Haifeng , Fu Qingxi , Wang Jiuru
Published: November 2024

Background

The methods used to detect epileptic seizures using electroencephalogram (EEG) signals suffer from poor accuracy in feature selection and high redundancy. This problem is addressed through the use of a novel multi-domain feature fusion and selection method (PMPSO).

Method

Discrete Wavelet Transforms (DWT) and Welch are used initially to extract features from different domains, including frequency domain, time-frequency domain, and non-linear domain. The first step in the detection process is to extract important features from different domains, such as frequency domain, time-frequency domain, and non-linear domain, using methods such as Discrete Wavelet Transform (DWT) and Welch. To extract features strongly correlated with epileptic classification detection, an improved particle swarm optimization (PSO) algorithm and Pearson correlation analysis are combined. Finally, Support Vector Machines (SVM), Artificial Neural Networks (ANN), Random Forest (RF) and XGBoost classifiers are used to construct epileptic seizure detection models based on the optimized detection features.

Result

According to experimental results, the proposed method achieves 99.32% accuracy, 99.64% specificity, 99.29% sensitivity, and 99.32% score, respectively.

Conclusion

The detection performance of the three classifiers is compared using 10-fold cross-validation. Surpassing other methods in detection accuracy. Consequently, this optimized method for epilepsy seizure detection enhances the diagnostic accuracy of epilepsy seizures.
Complex aortic valve repair in congenital patients: clinical feedback
Authors: Barbier Marie-Anne , Bulescu Nicolae Cristian , Metton Olivier , Bou Karam Lea , Martin Bonnet Caroline , Moulin Zinsch Anne , Lilot Marc , Henaine Roland
Published: November 2024

Introduction

In the congenital population, particularly in young adults, the best strategy for aortic valve surgery has not been clearly established. This study investigates the mortality, perioperative morbidity and echocardiographic evolution of complex aortic valve repair techniques.

Material and methods

We performed a retrospective monocentric descriptive study of patients operated at the Louis Pradel Hospital (Lyon) from 2017 to 2023. We included patients operated for complex aortic valve repair by the congenital heart surgery team, excluding simple commissurotomies. The primary endpoint was postoperative survival. The secondary endpoints were freedom from surgical reintervention and echocardiographic evolution of aortic regurgitation, aortic stenosis and annular diameter. The analysis was performed using Kaplan Meier methods.

Results

Twenty-eight patients were included. The mean age was 11.1 years (range 1–35 years) and the mean weight was 37.5 kg (range 8.2–79 kg). The postoperative survival rate was 96.4% at discharge (27/28 patients). The mean follow-up interval was 35 months (range 14–79 months). At the end of the follow-up, the freedom from reoperation was 85.7%. Four patients underwent reoperation for worsening aortic valve and/or ventricular function (1 heart transplantation, 2 Ross procedures, 1 aortic valve replacement). Results on secondary endpoints showed a trend towards improvement in annular diameter postoperatively between pre- and postoperative echocardiography for each patient, with no statistically significant difference for aortic insufficiency, but for aortic stenosis (p = 0.02).

Conclusion

This study shows an excellent survival rate, and a similar risk of reintervention compared with literature data. All the data described above argue in favor of an aortic valve repair surgery as a first line procedure in case of congenital heart disease.
Integrating RNA-seq and population genomics to elucidate salt tolerance mechanisms in flax (Linum usitatissimum L.)
Authors: Li Yuan-Dong , Li Xiao , Zhu Lei-Lei , Yang Yang , Guo Dong-Liang , Xie Li-Qiong
Published: November 2024

Salinity is an important abiotic environmental stressor threatening agricultural productivity worldwide. Flax, an economically important crop, exhibits varying degrees of adaptability to salt stress among different cultivars. However, the specific molecular mechanisms underlying these differences in adaptation have remained unclear. The objective of this study was to identify candidate genes associated with salt tolerance in flax using RNA-Seq combined with population-level analysis. To begin with, three representative cultivars were selected from a population of 200 flax germplasm and assessed their physiological and transcriptomic responses to salt stress. The cultivar C121 exhibited superior osmoregulation, antioxidant capacity, and growth under salt stress compared to the other two cultivars. Through transcriptome sequencing, a total of 7,459 differentially expressed genes associated with salt stress were identified, which were mainly enriched in pathways related to response to toxic substances, metal ion transport, and phenylpropanoid biosynthesis. Furthermore, genotyping of the 7,459 differentially expressed genes and correlating them with the phenotypic data on survival rates under salt stress allowed the identification of 17 salt-related candidate genes. Notably, the nucleotide diversity of nine of the candidate genes was significantly higher in the oil flax subgroup than in the fiber flax subgroup. These results enhance the fundamental understanding of salt tolerance mechanisms in flax, provide a basis for a more in-depth exploration of its adaptive responses to salt stress, and facilitate the scientific selection and breeding of salt-tolerant varieties.
Physiological characteristics during the formation of aromatic components in xylem of Aquilaria sinensis induced by exogenous substances
Authors: Pang Shengjiang , Li Zhongguo , Zhang Qingqing , Tian Zuwei , Deng Shuokun , Zhang Pei , Liu Shiling , Yang Baoguo , Zhou Zaizhi
Published: November 2024

An inductive combination of plant growth regulators, inorganic salts, and fungi is essential for the formation of aromatic components in the xylem of Aquilaria sinensis. However, the dynamics of xylem physiology and the relationships between physiological properties and aromatic components after artificial induction remain unclear. In this study, the changes in physiological properties of A. sinensis xylem during induction were determined and analyzed under four induction treatments and a control group. The defense hormone contents of jasmonic acid, salicylic acid, aminocyclopropane-1-carboxylic acid, and abscisic acid obtained from the four induction treatments increased significantly. However, the concentrations of gibberellin and indoleacetic acid were decreased compared to the control group. An initially upward and then downward trend was observed in the main antioxidant enzyme activities. Additionally, malonaldehyde content decreased obviously, while proline content tended to increase and then decrease as induction continued. The total and soluble sugar content was evidently reduced after treatment, and the soluble sugar content recovered more rapidly with time. Thirty-three aromatic components were identified in all treatments, and the primary aromatic components were terpenes, aromatics and chromones, the relative contents of which varied among treatments. These results provide new insights for optimization and innovation of agarwood induction techniques by exploring the formation of aromatics in the xylem of A. sinensis and its physiological responses following induction with exogenous substances (ethephon, NaCl, CaCl2 and fungal mixed solution).
Impact of the deep squat on articular knee joint structures, friend or enemy? A scoping review
Authors: Rojas-Jaramillo Andrés , Cuervo-Arango Daniel A. , Quintero Juan D. , Ascuntar-Viteri Juan D. , Acosta-Arroyave Natalia , Ribas-Serna Juan , González-Badillo Juan José , Rodríguez-Rosell David
Published: November 2024

Background

The squat exercise has been shown to improve athletic performance. However, the use of the deep squat has been questioned due to claims that it may cause knee joint injuries. Therefore, the purpose of this scoping review was to synthesize existing literature concerning the impact of deep squats on knee osteoarticular health in resistance-trained individuals.

Methods

This study adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses for Scoping Reviews (PRISMA-ScR) guidelines. The original protocol was prospectively registered in Figshare (https://doi.org/10.6084/m9.figshare.24945033.v1). A systematic and exhaustive search was conducted in different databases: PubMed, Scopus, Web of Science, and SPORTDiscus. Additional searches were performed in Google Scholar and PEDro. The main inclusion criteria were the following: (1) Articles of experimental, observational, or theoretical nature, including randomized controlled trials, longitudinal studies, case reports, integrative reviews, systematic reviews, and meta-analyses(Primary studies were required to have a minimum follow-up duration of 6 weeks, whereas secondary studies were expected to adhere to PRISMA or COCHRANE guidelines or be registered with PROSPERO; (2) Peer-reviewed articles published between 2000 and 2024; (3) Publications written in English, Spanish and Portuguese; (4) Studies reporting the effects of deep half, parallel or quarter squats on the knee or evaluating squats as a predictor of injury.

Results

The keyword search resulted in 2,274 studies, out of which 15 met all inclusion criteria. These 15 studies comprised 5 cohort studies, 3 randomized controlled trials, 4 literature or narrative reviews, 1 case study, and 2 systematic reviews, one including a meta-analysis. Overall, the risk of bias (ROB) across these studies was generally low. It is worth noting that only one study, a case study, associated deep squats with an increased risk of injury, the remaining 14 studies showed no negative impact of deep squats on knee joint health.

Conclusion

The deep squat appears to be a safe exercise for knee joint health and could be included in resistance training programs without risk, provided that proper technique is maintained.
Energy Metabolite, Immunity, Antioxidant Capacity, and Rumen Microbiota Differences Between Ewes in Late Gestation Carrying Single, Twin, and Triplet Fetuses
Authors: Chen Jiaxin , Duan Chunhui , Yue Sicong , Liu Xiaona , Li Jinhui , Zhang Yingjie , Liu Yueqin
Published: November 2024

The objective of this study was to investigate the differences in the energy metabolites, immunity, antioxidant capacity, and rumen microbiota of ewes with different numbers of fetuses. Thirty healthy ewes were selected and divided into single- (SL, n = 10), twin- (TL, n = 10), and triplet-fetal (PL, n = 10) ewes according to the number of fetuses. Sampling was carried out on days 21 (Q21) and 7 (Q7) before lambing. The results show no differences (p > 0.05) in the DMI and BW of ewes with different numbers of fetuses, and the body condition score (BCS) of PL ewes was lower (p < 0.05) than that of SL ewes. The concentrations of β-hydroxybutyric acid (BHBA), non-esterified fatty acids (NEFA), interleukin-2 (IL-2), interleukin-6 (IL-6), and tumor necrosis factor α (TNF-α) in the PL ewes were higher (p < 0.05), while the glucose (Glu), triglyceride (TG), total cholesterol (TC), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and total antioxidant capacity (T-AOC) values were lower (p < 0.05) than those of the SL ewes. ANOSIM analysis showed that the rumen bacterial structure of the SL, TL, and PL ewes was different on days Q21 and Q7. The relative abundance of Firmicutes and Bacteroidota in the rumen was affected (p < 0.05) by the number of fetuses: the relative abundance of Firmicutes (Ruminococcus, Butyrivibrio, Christensenellaceae_R-7_group, Lachnospiraceae_AC2044_group, Lachnospiraceae_XPB1014_group, and Anaeroplasma) was higher (p < 0.05), while that of Bacteroidota (Prevotella, Prevotellaceae_UCG-003, and Prevotellaceae_UCG-001) was lower (p < 0.05) in the SL ewes than in the PL ewes. In summary, the rumen microbial structure and energy metabolites of ewes in late gestation with different numbers of fetuses were different. Triplet-fetal ewes were characterized by lower BCS and antioxidant capacity and were prone to the triggering of inflammatory responses.
Leveraging Swarm Intelligence for Invariant Rule Generation and Anomaly Detection in Industrial Control Systems
Authors: Song Yunkai , Huang Huihui , Wang Hongmin , Wei Qiang
Published: November 2024

Industrial control systems (ICSs), which are fundamental to the operation of critical infrastructure, face increasingly sophisticated security threats due to the integration of information and operational technologies. Conventional anomaly detection techniques often lack the ability to provide clear explanations for their detection, and their inherent complexity can impede practical implementation in the resource-constrained environments typical of ICSs. To address these challenges, this paper proposes a novel approach that leverages swarm intelligence algorithms for the extraction of numerical association rules, specifically designed for anomaly detection in ICS. The proposed approach is designed to effectively identify and precisely localize anomalies by analyzing the states of sensors and actuators. Experimental validation using the Secure Water Treatment (SWaT) dataset demonstrates that the proposed approach can detect over 84% of attack instances, with precise anomaly localization achievable by examining as few as two to six sensor or actuator states. This significantly improves the efficiency and accuracy of anomaly detection. Furthermore, since the method is based on the general control dynamics of ICSs, it demonstrates robust generalization, making it applicable across a wide range of industrial control systems.
Analysis of VLF Electromagnetic Scattering in Lower Anisotropic Ionosphere Based on Transfer Matrix
Authors: Zhao Lin , Zhan Zhiting , Zhang Zhigang , Feng Huiting
Published: November 2024

Very-low-frequency (VLF) electromagnetic waves (3–30 kHz) are stable and attenuated, suitable for various applications in submarine communication and earthquake prediction. Very-low-frequency electromagnetic waves usually propagate in atmospheric waveguides formed between the anisotropic ionosphere at low to medium heights and the earth. However, the electromagnetic parameters of the anisotropic ionosphere at low to medium heights are very complex, making it difficult to accurately calculate and analyze the scattering characteristics of very-low-frequency electromagnetic waves. This article divides the mid to low altitude anisotropic ionosphere into fine layers, and establishes a more accurate transmission model for ultra-low-frequency electromagnetic waves in the layered structure of ionization layers by deriving the anisotropy/transmission matrix of each layer. In the comparative verification, we calculated the field strength of 17 kHz VLF electromagnetic waves within a transmission distance range of 500–1600 km based on the proposed method and compared it with statistical data collected from actual communication experiments and theoretical calculation results based on traditional ITU-R P.372-11. The results show that compared with the theoretical results based on ITU-R P.372-11, the method proposed in this paper fully considers the vertical height non-uniformity of the ionosphere, and its calculated results are more consistent with actual measurement data, with higher accuracy. Our work provides excellent guidance for the development of precise models for the propagation and prediction of extremely low-frequency electromagnetic waves, as well as a good idea for the accurate calculation of VLF electromagnetic scattering within 500–1500 km.
Window Coverage and Liquid Biopsy in the First-Line Therapy of Severe Sudden Sensorineural Hearing Loss
Authors: Kilgue Alexander , Kim Rayoung , Scholtz Lars-Uwe , Riemann Conrad , Pfeiffer Christoph J. , Schürmann Matthias , Todt Ingo
Published: November 2024

Introduction: Based on clinical practice guidelines, the application of corticosteroids as a first-line therapy is common. Although sudden sensorineural hearing loss (SSHL) etiology is primarily idiopathic, hearing loss can result from a perilymphatic fistula (PLF). Recent findings show evidence of a specific rate of PLF based on a cochlin-tomoprotein (CTP) detection test. Based on this rate of PLF treatment, the concepts of SSNHL need to be re-evaluated. The present study aimed to evaluate CTP in SSNHL patients and compare pre-surgical and post-surgical pure tone hearing thresholds after round and oval window sealing as first-line treatment. Material and Methods: A total of 30 patients with unilateral SSNHL with a pure tone average (PTA) (4 Freq. of 60 dB or more were enrolled in a prospective study. All patients underwent tympanoscopy for middle ear exploration as a first-line treatment. After intraoperative observation of a possible PLF, all patients obtained middle ear lavage to gain CTP samples for following ELISA-based CTP detection tests. All patients received round window and oval window sealing with fascia. PTA hearing thresholds were analyzed post-surgically 3 weeks after treatment based on 4-frequency bone conduction (BC). Results: The average preoperative pure tone BC threshold was 97.7 dB compared with the 69 dB postoperative BC threshold. Mean BC improved by 20.3 dB after middle ear exploration and window sealing. A total of 56% (17 of 30) of patients recovered at least 10 dB. The middle ear cochlin-tomoprotein detection rate was 70% positive. Conclusions: The combination of early tympanoscopy and inner ear-specific cochlin-tomoprotein as a detection tool for suspected PLF showed evidence of PLF as a key causative in SSNHL.
Architectural Design Studio Works Exploring Archetype Based on Ecological Sensibilities from Experiencing Najdi Architecture of At-Turaif Town and Modern Riyadh
Authors: Yun Suk Hee , Yi Tae Yeual
Published: November 2024

The numbness to human loss becomes ordinary. Indifference to human affairs seems normal after experiencing the global lockdown. Bringing up empathy becomes the most challenging task in architectural design studios after the COVID-19 pandemic. Examining otherness solidified after a global pandemic would be a way to revive empathy and to engage more in architectural design studios. The physiological disparity between the modern and the vernacular environments narrows down with the revival of Najdi architecture, the Salmani architecture style, and the Diriyah Gate Project in Riyadh, KSA. The disparity is caused by intangible factors such as speed, density, and tension but the revival focuses heavily on the tangible, formal expression. The architectural elements in the vernacular Najdi architecture have different meanings and roles beyond being a decorative motif. The feeble values of the vernacular undermined by touristic images are challenged by a series of radical design projects not to be generalized again by picturesque replicas of the past. Seeing the lost, the ecological sensibility of a community or collective that embraced the harshest land with full respect, might not be visual but is instead radically experiential, like a serendipitous breeze in Riyadh. This paper introduces a series of studio works that challenge how to bring back the living structure, in the harshest environment, to daily life through experimental and speculative design processes. It proposes how a community is called on to guard the environmental landscape, again defying the visual interpretation of Najdi architecture in a political landscape dominated by high fence walls.
Impact of MASLD on Portal Vein Thrombosis Following Hepatectomy for Liver Cancer
Authors: Wada Yoshito , Okuda Koji , Sasaki Shin , Shimose Shigeo , Nishida Takamichi , Shimokobe Hisaaki , Nagao Yuichi , Torigoe Takayuki , Hayashi Koji , Akashi Hidetoshi , Taniwaki Satoshi , Imamura Tetsuo
Published: November 2024

Background: Due to the increasing global prevalence of non-alcoholic fatty liver disease (NAFLD), which is closely linked to metabolic disorders, there has been a rise in the number of patients with NAFLD undergoing hepatectomy. The metabolic disorders, as well as NAFLD, increase venous thrombotic risk. NAFLD was recently updated to a new concept of hepatic steatosis: metabolic dysfunction-associated steatotic liver disease (MASLD). We aimed to investigate the impact of MASLD on post-hepatectomy portal vein thrombosis (PH-PVT). Methods: A total of 106 patients who underwent hepatectomy for liver cancer were included. Steatotic liver disease (SLD) was diagnosed using a CT L/S ratio of <1.1. SLD was classified as follows: MASLD, SLD associated with metabolic factors without alcohol consumption; MetALD, SLD with metabolic factors and moderate alcohol consumption; Other SLD, alcohol or other specific etiology of SLD; and No SLD, no hepatic steatosis. Results: PH-PVT was detected in 12/106 patients (11.3%); MASLD, 7/20 (35%); MetALD, 1/5 (20%); Other SLD, 1/13 (8%); and No SLD, 3/68 (4.4%). Multivariate analysis showed that the MASLD group (including MASLD and MetALD) (odds ratio [OR], 9.27) and left lateral sectionectomy (OR, 6.22) were significant independent risk factors for PH-PVT. Additionally, the incidence of PH-PVT was significantly higher in patients with MASLD than in those without SLD, along with metabolic factors, excluding alcohol consumption. Conclusions: MASLD and MetALD were identified as independent and significant risk factors for PH-PVT. Consideration was given to the idea that hepatic steatosis and metabolic dysfunction play synergistic roles in PH-PVT development.
Characterization of Breast Cancer Intra-Tumor Heterogeneity Using Artificial Intelligence
Authors: Lashen Ayat G. , Wahab Noorul , Toss Michael , Miligy Islam , Ghanaam Suzan , Makhlouf Shorouk , Atallah Nehal , Ibrahim Asmaa , Jahanifar Mostafa , Lu Wenqi , Graham Simon , Bilal Mohsin , Bhalerao Abhir , Mongan Nigel P. , Minhas Fayyaz , Raza Shan E Ahmed , Provenzano Elena , Snead David , Rajpoot Nasir , Rakha Emad A.
Published: November 2024

Intra-tumor heterogeneity (ITH) is a fundamental characteristic of breast cancer (BC), influencing tumor progression, prognosis, and therapeutic responses. However, the complexity of ITH in BC makes its accurate characterization challenging. This study leverages deep learning (DL) techniques to comprehensively evaluate ITH in early-stage luminal BC and provide a nuanced understanding of its impact on tumor behavior and patient outcomes. A large cohort (n = 2561) of early-stage luminal BC was evaluated using whole slide images (WSIs) of hematoxylin and eosin-stained slides of excision specimens. Morphological features of both the tumor and stromal components were meticulously annotated by a panel of pathologists in a subset of cases. A DL model was applied to develop an algorithm to assess the degree of heterogeneity of various morphological features per individual case utilizing defined patches. The results of extracted features were used to generate an overall heterogeneity score that was correlated with the clinicopathological features and outcome. Overall, 162 features were quantified and a significant positive correlation between these features was identified. Specifically, there was a significant association between a high degree of intra-tumor heterogeneity and larger tumor size, poorly differentiated tumors, highly proliferative tumors, tumors of no special type (NST), and those with low estrogen receptor (ER) expression. When all features are considered in combination, a high overall heterogeneity score was significantly associated with parameters characteristic of aggressive tumor behavior, and it was an independent predictor of poor patient outcome. In conclusion, DL models can be used to accurately decipher the complexity of ITH and provide extra information for outcome prediction.
Immunophenotypic Profile of Adult Glioblastoma IDH-Wildtype Microenvironment: A Cohort Study
Authors: Asioli Sofia , Gatto Lidia , Vardy Uri , Agostinelli Claudio , Di Nunno Vincenzo , Righi Simona , Tosoni Alicia , Ambrosi Francesca , Bartolini Stefania , Giannini Caterina , Franceschi Enrico
Published: November 2024

Background: Glioblastoma IDH-wildtype (GBM IDH-wt) is the most aggressive brain tumor in adults and is characterized by an immunosuppressive microenvironment. Different factors shaping its tumor microenvironment (TME) regulate tumor progression and treatment response. The aim of this study was to characterize the main immunosuppressive elements of the GBM IDH-wt TME. Methods: Immunohistochemistry for CD3, CD4, CD8, CD163, programmed death ligand 1 (PD-L1) and programmed death 1 (PD1) was performed on surgical tumor specimens from patients diagnosed with GBM IDH-wt, according to the CNS WHO 2021 criteria. The impact of categorical variables on time-dependent outcomes such as overall survival (OS) and progression-free survival (PFS) has been estimated through the Kaplan–Meier method. Results: We included 30 patients (19 males and 11 females), median age of 59.8 years (range 40.2–69.1 years). All patients underwent surgery followed by temozolomide concurrent with and adjuvant to radiotherapy. MGMT was methylated in 14 patients (47%) and unmethylated in 16 patients (53%). The overall absolute percentages of CD4+ lymphocytes, both intratumoral and perivascular, were significantly more represented than CD8+ lymphocytes in the TME (p = 0.02). A low density of CD4+ lymphocytes (≤10%) was found to be a favorable prognostic factor for GBM outcome (p = 0.02). Patients with MGMT methylated and unmethylated tumors exhibited a distinct TME composition, with a significant higher number of perivascular CD8+ lymphocytes (p = 0.002), intratumoral CD8+ lymphocytes (p = 0.0024) and perivascular CD4+ lymphocytes (p = 0.014) in MGMT unmethylated tumors. PD-L1 expression in tumor cell surface was observed in four tumors (13.3%), and PD1 expression in infiltrating T lymphocytes was observed in nine (30%) tumors, with predominantly perivascular distribution. Conclusions: MGMT methylated and unmethylated tumors exhibit different immune profiles, likely reflecting the different biology of these tumors. The expression of PD-L1 in GBM IDH-wt patients is confined to a small subpopulation. While we found a significant association between low CD4+ lymphocyte density (≤10%) and survival, given the small numbers of our cohort, the prognostic value of CD4+ lymphocyte density will need to be validated in large-scale studies.
Small Leucine Zipper Protein Regulates Glucose Metabolism of Prostate Cancer Cells via Induction of Phosphoglycerate Kinase 1
Authors: Han Sila , Park Sungyeon , Kim Suhyun , Kwon Sujin , Ko Jesang
Published: November 2024

Background: Cancer cells exhibit altered metabolism whereby glucose is preferentially utilized to produce lactate through aerobic glycolysis. The increase in lactate production creates an acidic microenvironment that supports tumor progression and metastasis. Human small leucine zipper protein (sLZIP) is involved in the transcriptional regulation of genes related to migration and invasion of prostate cancer. However, the role of sLZIP in modulating glucose metabolism in prostate cancer remains unknown. This study investigates whether sLZIP regulates the transcription of glycolysis-related genes to promote metabolic reprogramming in prostate cancer. Methods: Depletion of sLZIP resulted in the downregulation of several glycolytic genes, including glucose transporter 1, phosphofructokinase liver type, phosphoglycerate kinase 1 (PGK1), and lactate dehydrogenase. Among these, only PGK1 showed a prominent dose-dependent decrease in mRNA and protein expression after sLZIP silencing. Results: Mechanistically, increasing or decreasing sLZIP affected the promoter activity of PGK1 in a similar manner. Moreover, the absence of sLZIP attenuated the maximum glycolytic rate in prostate cancer cells. These results were further supported by a reduction in lactate secretion, glucose uptake, and ATP production in sLZIP-knockout prostate cancer cells. sLZIP deficiency hindered cancer growth, as demonstrated by proliferation assays. However, overexpression of PGK1 in sLZIP knockout cells resulted in recovery of aerobic glycolysis. Results of the xenograft experiment revealed that mice injected with sLZIP knockout cells exhibited a decrease in tumor mass compared to those injected with control cells. Conclusion: These findings suggest that sLZIP contributes to the metabolic reprogramming of prostate cancer cells via the transcriptional regulation of PGK1.
Cervical CT Angiography: The Advantage of Ultra-High-Resolution CT Versus Conventional HRCT
Authors: Ito Junji , Yamashiro Tsuneo , Tomita Hayato , Heianna Joichi , Murayama Sadayuki , Nishie Akihiro
Published: November 2024

Background/Objectives: Pre-treatment depiction of the cervical arteries is important for better intra-arterial infusion therapy of malignant head and neck tumors. There have not been any studies on the image quality of ultra-high-resolution computed tomography (U-HRCT) for cervical CT angiography (CTA). The aim of this study is to evaluate the advantages of U-HRCT over conventional HRCT for cervical CTA; Methods: Forty-one patients underwent cervical CTA prior to selective intra-arterial infusion chemotherapy for malignant head and neck tumors. Twenty-two patients were scanned on conventional HRCT, while the remaining nineteen on U-HRCT. U-HRCT super-high-resolution (SHR) mode was used in 8 patients, while high-resolution (HR) mode was used in 11 patients. On CTA, the visibility of 18 branches from bilateral external carotid arteries was evaluated using a 5-point scale by three radiologists in consensus. Prior to the patient study, a head–neck CT phantom study regarding mock arterial density and its visibility was performed; Results: Regarding the patient study, the mean score of the SHR mode for visibility was significantly higher than that of conventional HRCT in 17 of 18 arteries (p < 0.05). The mean score of the HR mode for visibility was significantly higher than that of conventional HRCT in all arteries (p < 0.05). Regarding the phantom study, the maximum density of the SHR mode was significantly higher than that of conventional HRCT for mock proximal and peripheral arteries (p < 0.01). In addition, the visual score of the SHR mode for mock arteries was significantly higher than that of conventional HRCT (p < 0.05); Conclusions: U-HRCT provides higher image quality in terms of visualization of the arteries than conventional HRCT in cervical CTA.
Precision Medicine for Metastatic Colorectal Cancer: Where Do We Stand?
Authors: Underwood Patrick W. , Pawlik Timothy M.
Published: November 2024

Metastatic colorectal cancer is a leading cause of cancer-related death across the world. The treatment paradigm has shifted away from systemic chemotherapy alone to include targeted therapy and immunotherapy. The past two decades have been characterized by increased investigation into molecular profiling of colorectal cancer. These molecular profiles help physicians to better understand colorectal cancer biology among patients with metastatic disease. Additionally, improved data on genetic pathways allow for specific therapies to be targeted at the underlying molecular profile. Investigation of the EGFR, VEGF, HER2, and other pathways, as well as deficient mismatch repair, has led to the development of multiple targeted therapies that are now utilized in the National Comprehensive Cancer Network guidelines for colon and rectal cancer. While these new therapies have contributed to improved survival for metastatic colorectal cancer, long-term survival remains poor. Additional investigation to understand resistance to targeted therapy and development of new targeted therapy is necessary. New therapies are under development and are being tested in the preclinical and clinical settings. The aim of this review is to provide a comprehensive evaluation of molecular profiling, currently available therapies, and ongoing obstacles in the field of colorectal cancer.
Dose-Reduced FLA-IDA in Combination with Venetoclax Is an Effective and Safe Salvage Therapy in Relapsed and Refractory Acute Myeloid Leukemia (R/R AML)
Authors: Schönrock Martin , Sonnemann Piet , Michalowski Nina , Heuser Michael , Thol Felicitas , Ayuk Francis Ayuketang , Wolschke Christine , Klyuchnikov Evgeny , Bokemeyer Carsten , Fiedler Walter , Cichutek Sophia
Published: November 2024

Background: Despite the development of targeted therapies in first-line AML, complete remissions (CR) cannot be achieved in 30–40%, and relapse rates remain high. In R/R AML the intensive treatment regimen of fludarabine, cytarabine, idarubicin combined with venetoclax (FLA-VIDA) showed improved remission rates compared to FLA-IDA. In this retrospective single-center analysis, we investigated the efficacy and safety of dose-reduced FLA-IDA with and without venetoclax to minimize the risk of infectious complications and excessive myelosuppression; Methods: Between 2011 and 2023, 89 R/R AML patients were treated with dose-reduced FLA-IDA (fludarabine 30 mg/m2 day 1–4, cytarabine 2000 mg/m2 day 1–4, idarubicin 10 mg/m2 day 1 + 4). From 2019 onwards, venetoclax was added (day 1 100 mg, day 2 200 mg, day 3–14 400 mg); Results: Significantly improved response rates were observed with 60.0% vs. 38.8% CR/CRi (p = 0.0297) and 74.5% vs. 47.3% (p = 0.032) CR/CRi/MLFS for FLA-VIDA vs. FLA-IDA. Further, with FLA-VIDA significantly improved event-free survival (EFS) was observed (p = 0.026). Overall survival (OS) was similar in FLA-VIDA and FLA-IDA treated patients. The most common treatment-related toxicities were hematological adverse events, but they were comparable between groups. The time to neutrophil and platelet recovery were similar in responding patients treated with FLA-VIDA vs. FLA-IDA; Conclusions: Dose-reduced FLA-VIDA significantly improved response rates without increases in toxicity, showing promise for an improved R/R AML treatment.
Clinical and Translational Landscape of Viral Gene Therapies
Authors: Yudaeva Alexandra , Kostyusheva Anastasiya , Kachanov Artyom , Brezgin Sergey , Ponomareva Natalia , Parodi Alessandro , Pokrovsky Vadim S. , Lukashev Alexander , Chulanov Vladimir , Kostyushev Dmitry
Published: November 2024

Gene therapies hold significant promise for treating previously incurable diseases. A number of gene therapies have already been approved for clinical use. Currently, gene therapies are mostly limited to the use of adeno-associated viruses and the herpes virus. Viral vectors, particularly those derived from human viruses, play a critical role in this therapeutic approach due to their ability to efficiently deliver genetic material to target cells. Despite their advantages, such as stable gene expression and efficient transduction, viral vectors face numerous limitations that hinder their broad application. These limitations include small cloning capacities, immune and inflammatory responses, and risks of insertional mutagenesis. This review explores the current landscape of viral vectors used in gene therapy, discussing the different types of DNA- and RNA-based viral vectors, their characteristics, limitations, and current medical and potential clinical applications. The review also highlights strategies to overcome existing challenges, including optimizing vector design, improving safety profiles, and enhancing transgene expression both using molecular techniques and nanotechnologies, as well as by approved drug formulations.
Extracellular Matrix as a Target in Melanoma Therapy: From Hypothesis to Clinical Trials
Authors: Mayasin Yuriy P. , Osinnikova Maria N. , Kharisova Chulpan B. , Kitaeva Kristina V. , Filin Ivan Y. , Gorodilova Anna V. , Kutovoi Grigorii I. , Solovyeva Valeriya V. , Golubev Anatolii I. , Rizvanov Albert A.
Published: November 2024

Melanoma is a malignant, highly metastatic neoplasm showing increasing morbidity and mortality. Tumor invasion and angiogenesis are based on remodeling of the extracellular matrix (ECM). Selective inhibition of functional components of cell–ECM interaction, such as hyaluronic acid (HA), matrix metalloproteinases (MMPs), and integrins, may inhibit tumor progression and enhance the efficacy of combination treatment with immune checkpoint inhibitors (ICIs), chemotherapy, or immunotherapy. In this review, we combine the results of different approaches targeting extracellular matrix elements in melanoma in preclinical and clinical studies. The identified limitations of many approaches, including side effects, low selectivity, and toxicity, indicate the need for further studies to optimize therapy. Nevertheless, significant progress in expanding our understanding of tumor biology and the development of targeted therapies holds great promise for the early approaches developed several decades ago to inhibit metastasis through ECM targeting.
Biodiversity and Abundance of Angiosperms and Environmental Resilience in the Tidal Range of Yuanjiang Dry–Hot Valley, Southwestern China
Authors: Yang Fengchun , He Qiong , Huang Huaping , Cui Yanmei , Gou Jianyong , Sarathchandra Chaya , Prueksakorn Kritana , Hashimoto Kiyota , Liu Li
Published: November 2024

Yuanjiang dry–hot valley is located in the southwest of mainland China. It is a sparsely vegetated area with a fragile arid ecosystem. Although the valley previously had forest cover, it has become a tropical montane savannah in recent decades. Mechanisms controlling plant species distribution in such dry–hot valleys are unclear. Clarifying this will be beneficial to sustainable ecosystem management in dry–hot valleys. This study explored the relationship between diversity patterns of plant species and their environments in the lowland of this dry–hot valley. To achieve this, transects and plots were arranged along the river channel. Alpha and beta diversity indices were calculated to quantify biodiversity changes between species and environments. Estimated species, rarity, and abundance indices were also utilized to examine the correlation among species, their population size, and their environment: Species_estimated (expected number of species in t pooled plots), Singletons (the number of species with only one individual in t pooled plots), Uniques (the number of species living in one plot in t pooled plots), ACE (species richness estimator with coverage-based abundance), ICE (species richness estimator with coverage-based incidence), and Chao2 (species richness estimator extrapolated from Singletons). Fifty years of meteorological records, including temperature and precipitation, were utilized as climate variables. The results indicated the following findings: (1) alpha diversity was higher closer to the river, whereas the beta diversity was higher towards the lower sections of the river (Bray–Curtis < 0.5), but this trend was reversed in the perpendicular transects; (2) total phosphorous (TP) and total potassium (TK) were higher on flatter ground, tending to be associated with raised nitrogen (TN) and organic matter (OM); (3) soil nutrients were higher towards the lower sections of the river, corresponding to an increased number of species; (4) water supply determined plant distribution, with soil condition determining water retention; (5) the estimated species and their rarity and abundance indices were associated with proximity to the river, indicating heterogeneity of habitats and soil condition; and (6) fern species could be used as indicators representing the xeric environment of Yuanjiang dry–hot valley. Plant cover was reduced at low altitudes, with high temperatures and a low water supply. These results draw attention to the need for specific policy formation to protect the microhabitats and manage the environment of the Yuanjiang valley.
Thinning Modulates the Soil Organic Carbon Pool, Soil Enzyme Activity, and Stoichiometric Characteristics in Plantations in a Hilly Zone
Authors: Guo Jing , Tang Wenjie , Tu Haochuan , Zheng Jingjing , Wang Yeqiao , Yu Pengfei , Wang Guibin
Published: November 2024

Thinning, a core forest management measure, is implemented to adjust stand density and affect soil biogeochemical processes by changing biotic and abiotic properties. However, the responses of soil organic carbon (SOC), soil enzyme activity (EEA), and stoichiometry (EES) in plantations in hilly zones to thinning have received little attention. To test the hypothesis that thinning has regulatory effects on the SOC pool, EEA, and EES characteristics, field sampling and indoor analysis were conducted 9 years after thinning. Thinning significantly influenced the soil properties, especially in the topsoil, and significantly greater SOC and mineral-associated organic carbon (MAOC) contents were observed in the high-density treatment. The EEAs in the topsoil tended to increase with increasing density. SOC, MAOC, and C to phosphorus (C:P) had the greatest influence on the soil EEAs and EESs. Microbial metabolic limitations tended to change from nitrogen to phosphorus with increasing density. The soil properties, SOC fractions, available nutrients, and elemental stoichiometry drove microbial metabolic limitations and were significantly positively correlated with β-glucosidase, elemental stoichiometry, and EES. This study deepens our understanding of EEAs, SOC, and nutrient dynamics under thinning practices and elucidates how forest tending measures affect soil biogeochemical processes, thereby providing ideas for developing strategies to mitigate the adverse impacts of human interventions.
Enhancing Silvicultural Practices: A Productivity and Quality Comparison of Manual and Semi-Mechanized Planting Methods in KwaZulu-Natal, South Africa
Authors: Khoza Mduduzi J. , Ramantswana Muedanyi M. , Spinelli Raffaele , Magagnotti Natascia
Published: November 2024

Planting plays a significant role in commercial forestry. Labour-related issues (scarcity, increased wages, absenteeism, ageing and high turnover), inconsistent work quality, increased operational costs, and poor ergonomics prompted the development of innovative planting techniques. This study aimed to assess the productivity (plants/productive machine hour), worker productivity (plants/worker PMH), work quality and tree survival of a manual and a semi-mechanised planting method. Two study sites at Flatcrown and Kwambonambi, consisting of 37 plots, were planted at 1333 stems/ha, alternating across the study sites. Block-level and elemental-level time studies were conducted, followed by work quality assessments. The manual method planted 7.23 ha/shift (Flatcrown) and 5.89 ha/shift (Kwambonambi), whilst the semi-mechanised method planted 4.72 ha/shift (Flatcrown) and 3.19 ha/shift (Kwambonambi). The manual method was 50% to 60% more productive (plants/PMH) than the semi-mechanised method. In terms of plants/worker PMH, higher worker efficiency of 30%–40% was observed at the Flatcrown site, which was characterised by level terrain and low residue presence compared to the Kwambonambi site, which had a gentle (<20%) terrain and medium residue presence. Planting quality was conducted according to planting specifications. The two methods did not significantly differ, although the study suggests that the proportion of good-quality plantings could be somewhat higher for the manual method. There was no significant difference in tree survival across methods and sites after one month.
Prognostic Relevance of Copy Number Losses in Ovarian Cancer
Authors: Jemma Andrea , Ardizzoia Alessandra , Redaelli Serena , Bentivegna Angela , Lavitrano Marialuisa , Conconi Donatella
Published: November 2024

Background/Objectives: Aneuploidy is a prevalent cancer feature that occurs in many solid tumors. For example, high-grade serous ovarian cancer shows a high level of copy number alterations and genomic rearrangements. This makes genomic variants appealing as diagnostic or prognostic biomarkers, as well as for their easy detection. In this study, we focused on copy number (CN) losses shared by ovarian cancer stem cells (CSCs) to identify chromosomal regions that may be important for CSC features and, in turn, for patients’ prognosis. Methods: Array-CGH and bioinformatic analyses on three CSCs subpopulations were performed. Results: Pathway and gene ontology analyses on genes involved in copy number loss in all CSCs revealed a significant decrease in mRNA surveillance pathway, as well as miRNA-mediated gene silencing. Then, starting from these CN losses, we validated their potential prognostic relevance by analyzing the TCGA cohort. Notably, losses of 4q34.3-q35.2, 8p21.2-p21.1, and 18q12.2-q23 were linked to increased genomic instability. Loss of 18q12.2-q23 was also related to a higher tumor stage and poor prognosis. Finally, specific genes mapping in these regions, such as PPP2R2A and TPGS2A, emerged as potential biomarkers. Conclusions: Our findings highlight the importance of genomic alterations in ovarian cancer and their impact on tumor progression and patients’ prognosis, offering advance in understanding of the application of numerical aberrations as prognostic ovarian cancer biomarkers.