bluuebunny/crossref_metadata_2025 huggingface dataset:
Development and validation of a nomogram for predicting motoric cognitive risk syndrome among community-dwelling older adults in China: a cross-sectional study
Authors: Yuan Huiqi , Jiang Ye , Li Yali , Bi Lisha , Zhu Shuhong
Published: November 2024

Background

Motoric cognitive risk (MCR) syndrome is characterized by slow gait speed and subjective cognitive complaints (SCC) and increases the risk of dementia and mortality.

Objective

This study aimed to examine the clinical risk factors and prevalence of MCR in community-dwelling older adults, with the goal of developing and validating a nomogram model for developing prevention strategies against MCR.

Methods

We enrolled community-dwelling participants aged 60–85 years at Guangwai Community Health Service Center between November 2023 and January 2024. A total of 1,315 older adults who met the criteria were randomly divided into a training set (n = 920) and a validation set (n = 395). By using univariate and stepwise logistic regression analysis in the training set, the MCR nomogram prediction model was developed. The area under the receiver operator characteristic curve (AUC), calibration plots, and Hosmer-Lemeshow goodness of fit test were used to evaluate the nomogram model’s predictive performance, while decision curve analysis (DCA) was used to evaluate the model’s clinical utility.

Results

Education, physical exercise, hyperlipoidemia, osteoarthritis, depression, and Time Up and Go (TUG) test time were identified as independent risk factors and were included to develop a nomogram model. The model exhibited high accuracy with AUC values of 0.909 and 0.908 for the training and validation sets, respectively. Calibration curves confirmed the model’s reliability, and DCA highlighted its clinical utility.

Conclusion

This study constructs a nomogram model for MCR with high predictive accuracy, which provides a reference for large-scale early identification and screening of high-risk groups for MCR.
A meta-analysis of the efficacy of physical exercise interventions on activities of daily living in patients with Alzheimer's disease
Authors: Xiao Yang , Fan Yu , Feng Zhengteng
Published: November 2024

Objective

This study aimed to systematically review published randomized controlled trials on the effects of physical exercise on activities of daily living (ADL) in Alzheimer's patients through meta-analysis, thereby synthesizing existing evidence to provide scientific intervention recommendations for exercise prescriptions in Alzheimer's patients.

Methods

Based on strict literature inclusion and exclusion criteria, a systematic search was conducted in databases including PubMed and Web of Science from their inception to July 1, 2024. The Cochrane risk assessment tool was used to evaluate the design of randomized controlled trials. Studies reporting on physical exercise interventions for ADL in Alzheimer's patients were systematically identified. Subgroup analyses and meta-regression were performed to explore sources of heterogeneity.

Results

Nineteen articles, for analysis, providing 27 randomized controlled trials (RCTs). A random-effects model was used to calculate the effect size and 95% confidence interval for each independent study, and meta-analysis was performed using Stata 16.0 and RevMan 5.4 software. The results showed that physical exercise might significantly improve ADL in Alzheimer's patients (SMD = 0.33, 95% CI: 0.12–0.54, I2 = 81.7%). Sensitivity analysis confirmed the robustness of the results (p > 0.05). Egger's test did not reveal significant publication bias (p = 0.145). Samples were divided into different subgroups based on intervention content, duration, frequency, and session length. Subgroup analysis based on intervention characteristics showed that resistance training or aerobic exercise (SMD = 0.83, 95% CI: 0.60–1.05), long-term interventions (>6 months, SMD = 0.31, 95% CI: 0.13–0.49), medium-frequency interventions (4-5 times per week, SMD=0.39, 95% CI: 0.23-0.55), and short-duration training ( ≤ 30 min, SMD = 0.96, 95% CI: 0.71–1.21) might be most effective in enhancing ADL in Alzheimer's patients. These improvements were not only statistically significant but also had substantial impact in clinical practice.

Conclusion

Resistance training or aerobic exercise lasting more than 6 months, 4–5 times per week, and lasting no more than 30 min per session may be most effective in improving ADLs in patients with Alzheimer's disease.
Operational considerations for approximating molecular assembly by Fourier transform mass spectrometry
Authors: Weiss Gabriella M. , Asche Silke , McLain Hannah , Chung Angela H. , Mehr S. Hessam M. , Cronin Leroy , Graham Heather V.
Published: November 2024

Some of the most common life detection techniques for planetary exploration focus on organic molecule characterization, but life on other planets may not chemically resemble that found on Earth. Therefore, an agnostic detection system of signs of life (biosignatures) is essential. Assembly Theory (AT) is a conceptual tool for understanding evolution and object formation that has been useful in developing an approach to quantify molecular complexity via the Molecular Assembly index, which when combined with abundance, allows the total assembly number of a sample to be calculated. Because AT makes no assumptions about the chemistry of life, it is an agnostic tool that identifies molecular structures that are probabilistically more likely to have arisen via selection and therefore biological processes. AT uses graph theory to quantify molecular complexity by finding the shortest sequence of joining operations (e.g., chemical bonds) required to build a compound from a set of starting materials allowing recursive reuse of units or fragments. For molecules, this number of steps is the MA value. We explore the use of Fourier transform (i.e., Orbitrap) mass spectrometry for approximating MA by quantifying how a molecule breaks apart into fragments. We analyze amino acid and nucleoside standards individually and as mixtures, as well as amino acids from naturally occurring biological and meteoritic sources. Aside from sample type, we evaluate the effect of analyte concentration and fragmentation energies on the generated MA value. Additionally, an older Orbitrap model similar to flight prototype instrumentation, was tested. The raw mass spectrometry data was compared with two different MA processing algorithms - one that uses the parent molecule spectrum and molecular weight (recursive) and one that does not (non-recursive). Concentration, fragmentation energy, and sample type all influence the raw mass spectra. However, the recursive algorithm reports MA estimates that are more consistent across sample types, concentrations, and fragmentation energies. We discuss instrument requirements for approximating MA that can be applied to future flight and sample return missions.
Case report: Placental chorioadenoma in a primiparous pug dog
Authors: Balogh Orsolya , Diab Santiago , Parker Acadia , de Sousa Gabriela C. , Cecere Julie T. , McCarter Samantha J. , Sponenberg Dan Phillip
Published: November 2024

A single 1.7 cm × 1.2 cm × 1 cm focal, raised, smooth, round, pink to flesh-colored mass protruding from the chorioallantois of the zonary placenta was found during Cesarean section in a primiparous pug bitch. Microscopically, the non-encapsulated, non-infiltrative, exophytic mass originated from the chorioallantoic stroma overlying the labyrinth and was composed of many arborizing fronds generally lined by 1 to 2 layers of cuboidal, columnar and occasionally polygonal, large trophoblastic cells, but frequently by a larger number of cells that occasionally piled up to form small nests or nodules. The gross and microscopic characteristics of this mass were compatible with a benign neoplastic process arising in the chorioallantois and involving placental trophoblasts, hence the diagnosis of a placental chorioadenoma. Five of the six newborn puppies were viable and of normal birthweight, while one puppy, which had lower birthweight than the others, could not be resuscitated and was humanely euthanized. Although placental tumors in dogs are very rare, this case is compelling evidence in the argument for routine inspection of canine placentas to identify potentially deleterious macro- or microscopic conditions that may be linked to negative fetal outcomes.
The Effect of Rearing and Adult Environment on HPA Axis Responsivity and Plumage Condition in Laying Hens
Authors: Nordgreen Janicke , Dumontier Lucille , Smulders Tom V. , Vas Judit , Palme Rupert , Janczak Andrew M.
Published: November 2024

The hypothalamic–pituitary–adrenal (HPA) axis responsivity is influenced by early life experience and also modified by the environment an individual experiences as an adult. Because laying hens are transferred from rearing to laying farms at 16–18 weeks of age, they are well suited to study the interaction effect between early (rearing) and adult (laying) environments on physiology and behaviour. In the European Union, there is a move towards cage-free systems for laying hens, but globally, the majority of layers are kept in conventional or furnished cages. Conventional cages have no enrichment, whereas furnished cages have little enrichment. Both cage types limit the movement of birds and the expression of highly motivated behaviours. Lack of enrichment may lead to under-stimulated birds that are more sensitive to stress and fear-inducing challenges later in life. Fearfulness has been linked to feather pecking, which has negative consequences for animal welfare and productivity. Previous research has shown that birds reared in cages are more fearful and perform more poorly in a test of spatial cognition than birds reared in aviaries when tested within five weeks after transition to adult housing. However, recent results suggest that these effects might not be long-lasting. We, therefore, tested the effect of the early (rearing) (aviary vs. cage) and adult (laying) environments (standard vs. additionally enriched furnished cages) on the corticosterone response to restraint in birds that were 35 weeks into lay (i.e., 52 weeks of age) and assessed their plumage condition. We hypothesised that a lower level of enrichment, both during rearing and adulthood, would represent a lower level of stimulation, resulting in a stronger corticosterone response to restraint and poorer feather cover. Both stressed (restrained) and control birds increased their corticosterone levels from the first (baseline) to second sample (p < 0.01 for both), but the increase in the restrained group was significantly higher than in the control group (F1, 111 = 9.51; p = 0.003). There was no effect of the early environment, but birds housed in standard furnished cages as adults had overall higher corticosterone levels than birds housed in enriched furnished cages regardless of their early life environment (F1, 51 = 4.12; p = 0.048). Neither early nor adult housing influenced the feather score except for on the belly, where birds housed in enriched cages as adults had a poorer feather score, contrary to our prediction. In conclusion, no effect of the early environment on HPA axis responsivity to an acute stressor could be detected at 52 weeks of age, but adult enrichment had a favourable effect on overall corticosterone levels.
Phytase Improves Zinc Utilization by Broiler Chickens
Authors: Maria Douglas Drebes Brunhaus , Vieira Sergio Luiz , Horn Raquel Medeiros , Marchi Maria Luísa Adachi , Favero Andre
Published: November 2024

The study aimed to evaluate phytase effects on the availability of zinc (Zn) from corn and soybean meal feeds for broiler chickens, whereas, in parallel, Zn requirements were investigated. A total of 640 Cobb × Cobb 500 male chicks were fed a Zn-deficient diet (18.87 ± 0.87 mg/kg Zn) until 7 days of age. The experiment was a 2 × 5 factorial with 10 treatments (feeds with or without phytase × 5 increasing dietary Zn levels) with 8 replications of 8 birds each. Supplemental Zn sulfate heptahydrate was used (measurements of the Zn analyzed in the feeds were 30.1 ± 0.73, 61.6 ± 0.13, 90.4 ± 1.60, 123.6 ± 1.99, and 151.9 ± 1.84 mg/kg, respectively). There were no interactions between phytase and Zn for any evaluated response. Phytase improved broiler performance and increased plasma myo-inositol, Zn content in the liver and tibia, Zn retention, and digestible energy (p < 0.05). No significant impact of dietary Zn was found on broiler performance (p > 0.05) except for Zn excretion and tibia Zn content. Adding phytase at 4000 FYT increased the apparent ileal Zn digestibility by 98% and Zn retention by 13.7%, whereas Zn supplementation of up to 151.9 mg/kg did not impact broiler performance.
Contamination Survey of Insect Genomic and Transcriptomic Data
Authors: Zhou Jiali , Zhang Xinrui , Wang Yujie , Liang Haoxian , Yang Yuhao , Huang Xiaolei , Deng Jun
Published: November 2024

The rapid advancement of high-throughput sequencing has led to a great increase in sequencing data, resulting in a significant accumulation of contamination, for example, sequences from non-target species may be present in the target species’ sequencing data. Insecta, the most diverse group within Arthropoda, still lacks a comprehensive evaluation of contamination prevalence in public databases and an analysis of potential contamination causes. In this study, COI barcodes were used to investigate contamination from insects and mammals in GenBank’s genomic and transcriptomic data across four insect orders. Among the 2796 WGS and 1382 TSA assemblies analyzed, contamination was detected in 32 (1.14%) WGS and 152 (11.0%) TSA assemblies. Key findings from this study include the following: (1) TSA data exhibited more severe contamination than WGS data; (2) contamination levels varied significantly among the four orders, with Hemiptera showing 9.22%, Coleoptera 3.48%, Hymenoptera 7.66%, and Diptera 1.89% contamination rates; (3) possible causes of contamination, such as food, parasitism, sample collection, and cross-contamination, were analyzed. Overall, this study proposes a workflow for checking the existence of contamination in WGS and TSA data and some suggestions to mitigate it.
Molecular Pathophysiology of Chronic Thromboembolic Pulmonary Hypertension: A Clinical Update from a Basic Research Perspective
Authors: Gonzalez-Hermosillo Leslie Marisol , Cueto-Robledo Guillermo , Navarro-Vergara Dulce Iliana , Torres-Rojas Maria Berenice , García-Cesar Marisol , Pérez-Méndez Oscar , Escobedo Galileo
Published: November 2024

Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare but severe condition characterized by persistent obstruction and vascular remodeling in the pulmonary arteries following an acute pulmonary embolism (APE). Although APE is a significant risk factor, up to 25% of CTEPH cases occur without a history of APE or deep vein thrombosis, complicating the understanding of its pathogenesis. Herein, we carried out a narrative review discussing the mechanisms involved in CTEPH development, including fibrotic thrombus formation, pulmonary vascular remodeling, and abnormal angiogenesis, leading to elevated pulmonary vascular resistance and right heart failure. We also outlined how the disease’s pathophysiology reveals both proximal and distal pulmonary artery obstruction, contributing to the development of pulmonary hypertension. We depicted the risk factors predicting CTEPH, including thrombotic history, hemostatic disorders, and certain medical conditions. We finally looked at the molecular mechanisms behind the role of endothelial dysfunction, gene expression alterations, and inflammatory processes in CTEPH progression and detection. Despite these insights, there is still a need for improved diagnostic tools, biomarkers, and therapeutic strategies to enhance early detection and management of CTEPH, ultimately aiming to reduce diagnostic delay and improve patient outcomes.
Examining the Spatial and Temporal Variation of PM2.5 and Its Linkage with Meteorological Conditions in Dhaka, Bangladesh
Authors: Rahman Mizanur , Meng Lei
Published: November 2024

This study investigates the temporal and spatial variations in PM2.5 concentrations in Dhaka, Bangladesh, from 2001 to 2023 and evaluates the impact of meteorological factors and the effectiveness of mitigation strategies on air pollution. Using satellite and ground-based data, this study analyzed the seasonal trends, daily fluctuations, and the influence of COVID-19 lockdown measures on air quality. Our findings reveal a persistent increase in PM2.5 levels, particularly during winter, with concentrations frequently exceeding WHO guidelines. Our analysis suggests significant correlations between meteorological conditions and PM2.5 concentration, highlighting the significant role of meteorological conditions, such as rainfall, humidity, and temperature, in modulating PM2.5 levels. Our analysis found that PM2.5 levels exhibited a significant inverse correlation with relative humidity (r = −0.72), rainfall (r = −0.69), and temperatures (r = −0.79), highlighting the role of meteorological conditions in mitigating pollution levels. Additionally, the study underscores the temporary improvements in air quality during lockdown periods, demonstrating the potential benefits of sustained emission control measures. The research emphasizes the need for comprehensive and multi-faceted air quality management strategies, including stringent vehicular and industrial emissions regulations, enhancement of urban green spaces, and public awareness campaigns to mitigate the adverse health impacts of PM2.5 pollution in Dhaka.
Perceptual-Motor Abilities and Reversal Frequency of Letters and Numbers in Children Diagnosed with Poor Reading Skills
Authors: Ibrahimi Danjela , Aviles Marcos , Rodríguez-Reséndiz Juvenal
Published: November 2024

Purpose: This paper investigated the visual–perceptual and visual–motor skills and the reversal frequency of letters and numbers that mirror one another in one hundred children aged 6–13 years diagnosed with poor reading skills. Methods: TVPS-4th, VMI-6th, and RFT were performed. Age and sex analysis was carried out. The impact of the eye movement patterns in the perceptual–motor skills and laterality–directionality concepts was also estimated to determine the relationship among tests to predict future results. Results: Most children scored between average and 3 stds below average on the motor VMI-6th test, while half of the participants scored between average and 2 stds below average on TVPS-4th. In the RFT, the majority scored between average and 1.5 stds below average. Participants scored higher on the spatial relationship subtest of the TVPS-4th and lower in the VMI-6th test (p<0.001). Statistically significant differences were found between the youngest and oldest participants on the TVPS-4th overall performance, as well as VD, FC and VFG skills (p<0.05). A strong relationship was found between the TVPS-4th and VMI-6th, (p<0.001). RFT results were different among all groups (p<0.05). The RFT was better related to the VMI-6th than TVPS-4th; however, it was statistically insignificant. The horizontal component of the DEM test was the best predictor for the TVPS-4th and ratio for the RFT, without attaining statistical significance. No sex differences were found. Conclusions: Results showed that children with poor reading skills exhibit perceptual–motor and reversal frequency difficulties, which are independent of the oculomotor performance. Considering that visual and motor processing are essential elements of the reading and writing process, their evaluation and treatment should be included as part of the multidisciplinary approach for children with poor reading skills. This would boost the general outcome and contribute to their academic achievement.
Precision Treatment of Metachronous Multiple Primary Malignancies Based on Constructing Patient Tumor-Derived Organoids
Authors: Wang Yicheng , Chen Haotian , Zhang Zhijin , He Yanyan , Liu Ji , Zhao Baoshuang , Wang Qinwan , Xu Jiangmei , Mao Shiyu , Zhang Wentao , Yao Xudong , Li Wei
Published: November 2024

When a patient has two or more primary tumors, excluding the possibility of diffuse, recurrent, or metastatic, they can be defined as having multiple primary malignant neoplasms (MPMNs). Moreover, cases of three primary urinary tract tumors are very rare. Here, we reported a patient of MPMNs with four primary tumors, including three urinary tract cancers (renal cancer, prostate cancer, and bladder cancer) and lung cancer. The four tumors appeared over 13 years, and pathological results confirmed that they were all primary tumors after different surgeries. In addition, we established patient-derived organoids (PDOs) by collecting tumor specimens. Hematoxylin-eosin (H&E) staining of PDOs showed that the organoids were histopathological consistent with parental tumor. Immunohistochemistry showed that PDOs can also reflect the expression of pathological markers in patients. At the same time, PDOs may also serve as “avatars” of patients to predict sensitivity to different drugs. In summary, we reported a case of MPMNs with four primary tumors and established PDOs from its tumor specimens. A personalized treatment strategy was established based on the histopathological characteristics of the organoids.
Laser Emission at 675 nm: Molecular Counteraction of the Aging Process
Authors: Notari Lorenzo , Pieri Laura , Cialdai Francesca , Fusco Irene , Risaliti Chiara , Madeddu Francesca , Bacci Stefano , Zingoni Tiziano , Monici Monica
Published: November 2024

Background/Objectives: Many lasers applied in skin rejuvenation protocols show emissions with wavelengths falling in the red or near-infrared (NIR) bands. To obtain further in vitro data on the potential therapeutic benefits regarding rejuvenation, we employed a 675 nm laser wavelength on cultured human dermal fibroblasts to understand the mechanisms involved in the skin rejuvenation process’s signaling pathways by analyzing cytoskeletal proteins, extracellular matrix (ECM) components, and membrane integrins. Methods: Normal human dermal fibroblasts (NHDFs) were irradiated with a 675 nm laser 24 h after seeding, and immunofluorescence microscopy and Western blotting were applied. Results: The results demonstrate that the laser treatment induces significant changes in human dermal fibroblasts, affecting cytoskeleton organization and the production and reorganization of ECM molecules. The cell response to the treatment appears to predominantly involve paxillin-mediated signaling pathways. Conclusions: These changes suggest that laser treatment can potentially improve the structure and function of skin tissue, with interesting implications for treating skin aging.
New Advances in Cardiovascular Drugs: A Celebration of the 90th Birthday of Professor Akira Endo
Authors: Caturano Alfredo
Published: November 2024

In this Special Issue, we celebrate a giant of cardiovascular pharmacology, Professor Akira Endo, on the occasion of his 90th birthday [...]
In Vivo and Computational Studies on Sitagliptin’s Neuroprotective Role in Type 2 Diabetes Mellitus: Implications for Alzheimer’s Disease
Authors: Mani Vasudevan , Arfeen Minhajul
Published: November 2024

Background/Objectives: Diabetes mellitus (DM), a widespread endocrine disorder characterized by chronic hyperglycemia, can cause nerve damage and increase the risk of neurodegenerative diseases such as Alzheimer’s disease (AD). Effective blood glucose management is essential, and sitagliptin (SITG), a dipeptidyl peptidase-4 (DPP-4) inhibitor, may offer neuroprotective benefits in type 2 diabetes mellitus (T2DM). Methods: T2DM was induced in rats using nicotinamide (NICO) and streptozotocin (STZ), and biomarkers of AD and DM-linked enzymes, inflammation, oxidative stress, and apoptosis were evaluated in the brain. Computational studies supported the in vivo findings. Results: SITG significantly reduced the brain enzyme levels of acetylcholinesterase (AChE), beta-secretase-1 (BACE-1), DPP-4, and glycogen synthase kinase-3β (GSK-3β) in T2DM-induced rats. It also reduced inflammation by lowering cyclooxygenase-2 (COX-2), prostaglandin E2 (PGE2), tumor necrosis factor-α (TNF-α), and nuclear factor-κB (NF-κB). Additionally, SITG improved oxidative stress markers by reducing malondialdehyde (MDA) and enhancing glutathione (GSH). It increased anti-apoptotic B-cell lymphoma protein-2 (Bcl-2) while reducing pro-apoptotic markers such as Bcl-2-associated X (BAX) and Caspace-3. SITG also lowered blood glucose levels and improved plasma insulin levels. To explore potential molecular level mechanisms, docking was performed on AChE, COX-2, GSK-3β, BACE-1, and Caspace-3. The potential binding affinity of SITG for the above-mentioned target enzymes were 10.8, 8.0, 9.7, 7.7, and 7.9 kcal/mol, respectively, comparable to co-crystallized ligands. Further binding mode analysis of the lowest energy conformation revealed interactions with the critical residues. Conclusions: These findings highlight SITG’s neuroprotective molecular targets in T2DM-associated neurodegeneration and its potential as a therapeutic approach for AD, warranting further clinical investigations.
Decoding Schizophrenia: How AI-Enhanced fMRI Unlocks New Pathways for Precision Psychiatry
Authors: Di Stefano Valeria , D’Angelo Martina , Monaco Francesco , Vignapiano Annarita , Martiadis Vassilis , Barone Eugenia , Fornaro Michele , Steardo Luca , Solmi Marco , Manchia Mirko , Steardo Luca
Published: November 2024

Schizophrenia, a highly complex psychiatric disorder, presents significant challenges in diagnosis and treatment due to its multifaceted neurobiological underpinnings. Recent advancements in functional magnetic resonance imaging (fMRI) and artificial intelligence (AI) have revolutionized the understanding and management of this condition. This manuscript explores how the integration of these technologies has unveiled key insights into schizophrenia’s structural and functional neural anomalies. fMRI research highlights disruptions in crucial brain regions like the prefrontal cortex and hippocampus, alongside impaired connectivity within networks such as the default mode network (DMN). These alterations correlate with the cognitive deficits and emotional dysregulation characteristic of schizophrenia. AI techniques, including machine learning (ML) and deep learning (DL), have enhanced the detection and analysis of these complex patterns, surpassing traditional methods in precision. Algorithms such as support vector machines (SVMs) and Vision Transformers (ViTs) have proven particularly effective in identifying biomarkers and aiding early diagnosis. Despite these advancements, challenges such as variability in methodologies and the disorder’s heterogeneity persist, necessitating large-scale, collaborative studies for clinical translation. Moreover, ethical considerations surrounding data integrity, algorithmic transparency, and patient individuality must guide AI’s integration into psychiatry. Looking ahead, AI-augmented fMRI holds promise for tailoring personalized interventions, addressing unique neural dysfunctions, and improving therapeutic outcomes for individuals with schizophrenia. This convergence of neuroimaging and computational innovation heralds a transformative era in precision psychiatry.
Diagnostic Utility of Metalloproteinases from Collagenase Group (MMP-1, MMP-8 and MMP-13) in Biochemical Diagnosis of Ovarian Carcinoma
Authors: Kicman Aleksandra , Gacuta Ewa , Marecki Rafał , Kicman Michał Stanisław , Kulesza Monika , Klank-Sokołowska Ewa , Knapp Paweł , Niczyporuk Marek , Szmitkowski Maciej , Ławicki Sławomir
Published: November 2024

Background: Ovarian carcinoma (OC) has an unfavorable prognosis due to lack of screening and an asymptomatic course. New diagnostic methods are being sought to enable earlier diagnosis of this condition. The purpose of this study was to determine the diagnostic utility of collagenases (MMP-1, MMP-8 and MMP-13) in the diagnosis of OC compared to HE4 and CA125 and the ROMA. Methods: The study group consisted of 120 patients with OC, the control group: 70 patients with benign ovarian lesions (BLs) and 50 healthy women (HS). MMP-1, MMP-8 and MMP-13 were determined by ELISA and HE4 and CA125 by CMIA. Results: OC patients had higher levels of MMP-1 and MMP-13 compared to the BL and HS groups. MMP-1 (SE: 81.66%; SP: 94%; PPV: 97.02%; NPV: 68.11%; AUC: 0.9625) and MMP-13 (SE: 77.50%; SP: 94%; PPV: 96.875%; NPV: 63.51%; AUC: 0.917) showed similar or higher diagnostic values to routine markers (HE4: SE:85%; SP: 92%; PPV: 96.22%; NPV: 71.875%; AUC: 0.943; CA125: SE: 80%; SP: 98%; PPV: 98.96%; NPV: 67.12%; AUC: 0.909) and the ROMA (SE: 90.83%; SP: 94%; PPV: 97.32%; NPV: 81.03%; AUC: 0.955). Performing combined analyses of individual MMPs and MMPs with ROMA was associated with further increases in diagnostic parameters. Conclusions: MMP-1 and MMP-13 have shown preliminary potential as diagnostic markers and auxiliary markers to ROMA in biochemical diagnosis of OC.
Cannabinoid-Induced Immunogenic Cell Death of Colorectal Cancer Cells Through De Novo Synthesis of Ceramide Is Partially Mediated by CB2 Receptor
Authors: Hengst Jeremy A. , Ruiz-Velasco Victor J. , Raup-Konsavage Wesley M. , Vrana Kent E. , Yun Jong K.
Published: November 2024

Background: Our recent studies have identified a link between sphingolipid metabolites and the induction of a specialized form of regulated cell death termed immunogenic cell death (ICD). We have recently demonstrated that the synthetic cannabinoid (±) 5-epi CP 55,940 (5-epi) stimulates the accumulation of ceramide (Cer), and that inhibition of sphingosine kinase 1 (SphK1) enhances Cer accumulation and ICD-induction in human colorectal cancer (CRC) cell lines. Methods: We employed flow-cytometric, western blot analyses, pharmacological inhibitors of the sphingolipid metabolic pathway and small molecule agonists and antagonists of the CB receptors to further analyze the mechanism by which 5-epi induces Cer accumulation. Results: Herein, and report that 5-epi induces de novo synthesis of Cer primarily through engagement of the cannabinoid receptor 2 (CB2) and depletion of intracellular calcium levels. Moreover, we report that 5-epi stimulates Cer synthesis through dysregulation of the endogenous inhibitor of the de novo Cer pathway, ORMDL3. We also observed a remarkable and specific accumulation of one Cer species, C20:4 Cer, generated predominantly by ceramide synthase 4, as a key factor required for 5-epi-induced ICD. Conclusions: Together, these data indicate that engagement of CB2, by 5-epi, alters regulation of the de novo ceramide synthesis pathway to generate Cer species that mediate ICD.
Targeting Epigenetic Alterations Linked to Cancer-Associated Fibroblast Phenotypes in Lung Cancer
Authors: Papavassiliou Kostas A. , Sofianidi Amalia A. , Gogou Vassiliki A. , Papavassiliou Athanasios G.
Published: November 2024

The focus in cancer research and treatment has recently shifted from being primarily tumor-centric to emphasizing the tumor microenvironment (TME) [...]
P53 and the Ultraviolet Radiation-Induced Skin Response: Finding the Light in the Darkness of Triggered Carcinogenesis
Authors: Carvalho Carla , Silva Rita , Melo Teresa M. V. D. Pinho e , Inga Alberto , Saraiva Lucília
Published: November 2024

This review delves into the significant cellular and molecular responses triggered by UVR exposure in human skin, emphasizing the pivotal role of mutant p53 (mutp53) in the carcinogenic process elicited by radiation. By underlining the role of a functional p53 in safeguarding skin cells from UVR-induced damage, this work underscores the potential significance of targeting mutp53, aiming to restore its wild-type-like activity (reactivation), as a protective strategy against skin cancer (SC), particularly NMSC. Most importantly, an interesting crosstalk between p53 and its vitamin D receptor (VDR) transcriptional target is also highlighted in the suppression of skin carcinogenesis, which opens the way to promising chemopreventive strategies involving synergistic combinations between mutp53 reactivators and vitamin D. Collectively, this review not only opens new avenues for future research, but also offers promising prospects for the development of novel beneficial approaches in the field of SC.
In Silico Design of Peptide Inhibitors Targeting HER2 for Lung Cancer Therapy
Authors: Alkhatabi Heba Ahmed , Alatyb Hisham N.
Published: November 2024

Background/Objectives: Human epidermal growth factor receptor 2 (HER2) is overexpressed in several malignancies, such as breast, gastric, ovarian, and lung cancers, where it promotes aggressive tumor proliferation and unfavorable prognosis. Targeting HER2 has thus emerged as a crucial therapeutic strategy, particularly for HER2-positive malignancies. The present study focusses on the design and optimization of peptide inhibitors targeting HER2, utilizing machine learning to identify and enhance peptide candidates with elevated binding affinities. The aim is to provide novel therapeutic options for malignancies linked to HER2 overexpression. Methods: This study started with the extraction and structural examination of the HER2 protein, succeeded by designing the peptide sequences derived from essential interaction residues. A machine learning technique (XGBRegressor model) was employed to predict binding affinities, identifying the top 20 peptide possibilities. The candidates underwent further screening via the FreeSASA methodology and binding free energy calculations, resulting in the selection of four primary candidates (pep-17, pep-7, pep-2, and pep-15). Density functional theory (DFT) calculations were utilized to evaluate molecular and reactivity characteristics, while molecular dynamics simulations were performed to investigate inhibitory mechanisms and selectivity effects. Advanced computational methods, such as QM/MM simulations, offered more understanding of peptide–protein interactions. Results: Among the four principal peptides, pep-7 exhibited the most elevated DFT values (−3386.93 kcal/mol) and the maximum dipole moment (10,761.58 Debye), whereas pep-17 had the lowest DFT value (−5788.49 kcal/mol) and the minimal dipole moment (2654.25 Debye). Molecular dynamics simulations indicated that pep-7 had a steady binding free energy of −12.88 kcal/mol and consistently bound inside the HER2 pocket during a 300 ns simulation. The QM/MM simulations showed that the overall total energy of the system, which combines both QM and MM contributions, remained around −79,000 ± 400 kcal/mol, suggesting that the entire protein–peptide complex was in a stable state, with pep-7 maintaining a strong, well-integrated binding. Conclusions: Pep-7 emerged as the most promising therapeutic peptide, displaying strong binding stability, favorable binding free energy, and molecular stability in HER2-overexpressing cancer models. These findings suggest pep-7 as a viable therapeutic candidate for HER2-positive cancers, offering a potential novel treatment strategy against HER2-driven malignancies.
Elevated Serum Direct Bilirubin and Smoking Status Are Prognostic Factors for EGFR-Mutated Non-Small Cell Lung Cancer Patients Receiving Tyrosine Kinase Inhibitor Therapy
Authors: Zhang Jingyuan , Zhang Yinwang , Lei Yuqiong , Zheng Qi , Gu Xiaohua , Liu Zeyu , Xu Yongle , Zhong Cheng , Shan Shan , Ren Tao
Published: November 2024

Lung cancer is one of the leading causes of cancer-related death worldwide [...]
µ-NMR Technology for Biomedical Applications: A Review
Authors: Sequeira-Antunes Beatriz , Ferreira Hugo Alexandre
Published: November 2024

Nuclear magnetic resonance (NMR) is a versatile method that non-invasively provides detailed insights into the atomic and molecular information of samples containing non-zero spin nuclei, facilitating observations of their structure, dynamics, and interactions. By miniaturizing NMR systems, micro-NMR (µ-NMR) devices overcome the limitations of traditional bulky NMR instruments, making them more portable, cost-effective, and suitable for a wide range of applications. As such, this review aims to provide a comprehensive overview of the recent advancements and potential applications of µ-NMR in the field of biomedicine. Beginning with an overview of the principles underlying NMR, this paper explains the fundamental concepts essential for understanding µ-NMR technology. It then delves into miniaturization techniques, detailing advancements in microcoils and probes and the development and integration with microfluidics, which have enhanced the sensitivity, portability, and versatility of µ-NMR devices. Ultimately, this review discusses the current biomedical applications of µ-NMR, including molecular imaging, metabolomics, biomarker detection, and point-of-care diagnosis, and highlights the potential of this technology to revolutionize precision medicine and healthcare. Despite the promising applications, challenges such as sensitivity, spectral resolution, and integration with other technologies are discussed, along with recent advances and innovations aimed at addressing these limitations.
Relationships Among Soda and Energy Drink Consumption, Substance Use, Mental Health and Risk-Taking Behavior in Adolescents
Authors: Suresh Surya , Temple Jennifer L.
Published: November 2024

Background/Objectives: Energy drink (ED) use is increasing among children and adolescents, but little is known about the impacts on health, including substance use and mental health. The purpose of this study was to examine the relationship between soda and ED consumption and substance use, mental health, and risk taking in a nationally representative sample of high school students. Methods: We used data from the 2019 Youth Risk Behavior Surveillance System (YRBS) from New Jersey, Montana, and Florida to assess these relationships using binary and multinomial regression analyses to determine odds ratios, comparing non-consumers with daily consumers. The sample was 10,548 adolescents (51.6% female) between the ages of 13–19 years. Results: Daily soda and ED consumption were associated with greater odds of substance use (OR(95% CI): 5.8 (3.7, 6.9)/10.2 (6.4, 16.3)), poorer mental health (OR(95% CI): 2.6 (1.3, 4.8)/1.8 (1.2, 2.8), and higher odds of eating fast food (OR(95% CI): 17.2 (8.9, 33)/10.6 (5.6, 19.9). These effects were moderated by sex. Conclusions: These findings suggest that soda and ED use are associated with greater risk taking among adolescents and that these relationships are moderated by sex. Future studies should determine the directionality of these relationships and examine the impact of reduced soda and ED consumption on health behaviors in children and adolescents.
Enhanced Protective Performance of Carbon Nanotube-Reinforced Waterborne Epoxy Zinc-Rich Coatings for Corrosion Protection of Steel Structures
Authors: Huang Xueling , Yang Chun , Chen Junyu , Qiao Xinglong , Zhang Shuguang , Song Dan
Published: November 2024

Carbon nanotube-reinforced waterborne epoxy zinc-rich coatings were developed by modifying waterborne epoxy zinc-rich formulations with varying amounts of carbon nanotubes (CNTs), to improve the coatings’ corrosion resistance and their protection for Q355b steel in environments rich in chlorides. A detailed investigation of the microstructural changes in the coatings prior to and following corrosion was conducted through FTIR, SEM, XRD, and XPS analytical techniques. The effectiveness of these innovative coatings in providing corrosion protection for Q355b steel in chloride conditions was assessed via electrochemical corrosion methodologies and neutral salt spray testing. The results indicate that an increase in the CNT concentration led to an initial enhancement in the corrosion resistance of the coatings, followed by a decrease, with optimal performance noted at 0.3 wt.% CNTs. During the electrochemical evaluations, the open circuit potential (OCP) of the coating containing 0.3 wt.% CNTs remained stable below the critical threshold of −0.78 V for an extended period, indicating sustained cathodic protection. In comparison to the coatings with CNT concentrations (wt.%) of 0.1, 0.5, 0.7, and 1.0, the coating with 0.3 wt.% CNTs demonstrated the lowest corrosion current density, measured at 0.0322 µA/cm2. Further validation of its exceptional corrosion resistance was provided by the 240 h neutral salt spray tests. This performance can be linked to the capability of the CNTs to improve electrical conductive connectivity between the zinc particles and the Q355b steel substrate beneath them, subsequently enhancing both the cathodic protection of the coating and its physical shielding effectiveness.
New Weak Keys with Parity Patterns in the RC4 Stream Cipher
Authors: Madarro-Capó Evaristo José , Legón-Pérez  Carlos Miguel , Sosa-Gómez Guillermo , Rojas Omar
Published: November 2024

The RC4 cryptographic algorithm is the most extensively studied stream cipher of the past two decades. This extensive research has resulted in numerous publications, many of which identify various vulnerabilities. Although these vulnerabilities do not preclude the correct use of the algorithm, they complicate its practical implementation. In this paper, we present a novel weakness in the RC4 cipher. Our findings indicate that, for input keys exhibiting certain patterns, the parity of the values in the output permutation of the KSA can be determined with high probability from the parity of its position in the output permutation. Furthermore, the use of keys with these specific patterns leads to noticeable distortions in several bytes of the RC4 output.
The Microstructural Evolution and Mechanical Properties of Boron-Doped Ti35Zr30V10Nb25 Refractory High-Entropy Alloy
Authors: Wang Xinggang , Sun Meng , Liu Jiaxin , Liu Xueqing , Jiang Weibin , Wang Xianping , Fang Qianfeng
Published: November 2024

The addition of oxygen or nitrogen in refractory high-entropy alloys (HEAs) has been widely reported, but studies on boron-doped HEAs have mainly focused on the segregation of boron elements at grain boundaries. The changes in the microstructure and mechanical properties in TiZrNb-based HEAs remain enigmatic. In this work, boron-doped Ti35Zr30V10Nb25 (Ti35-xB) refractory HEAs were designed to elucidate their microstructural evolution and mechanical properties. Unlike oxygen and nitrogen, trace amounts of boron addition result in the formation of borides, and boron exhibits a strong repulsion towards Zr, leading to Zr-depleted borides. Borides distributed along the grain boundaries refine the grain size and dendritic structure. The borides and structural refinement effect enhance the strain-hardening capacity and uniform elongation, resulting in an over 15% uniform elongation for Ti35-0.25B.
Non-Tuberculous Mycobacteria: Single Center Analyses of Risk Factors, Management and Mortality Outcomes of Adults with HIV
Authors: Nqwata Lamla , Pasipanodya Jotam G. , Black Marianne , Feldman Charles
Published: November 2024

Background/Objectives: In sub-Saharan Africa, there is paucity of data regarding non-tuberculous mycobacterial (NTM) infections, leading to underappreciation of disease burden. Consequently, fewer resources are allocated, leading to potential adverse outcomes. This study examines long-term mortality and risk factors of South African patients with positive NTM samples. Methods: We conducted a retrospective analysis of clinical isolates of NTMs between 1 January 2010 and 30 June 2017. We retrieved and thoroughly reviewed the corresponding medical records of patients treated at Charlotte Maxeke Johannesburg Academic Hospital. Outcomes were compared between patients who underwent different therapy regimens, including macrolide-based regimens and ‘watchful waiting’. Results: A total of 123 patients were followed for a median of 1 year (interquartile range [IQR], 0.5–4.5). The median age was 39 years (IQR, 31–51) with male predominance, 58%. The common comorbid conditions were HIV (encountered in 78%) and previous TB (58%). Pulmonary disease due to Mycobacterium avium complex (MAC-PD) was found in 74% of patients, M. fortiutum in 5%, and M. gordonae in 4%. The mortality relative risk for patients on initial macrolide-containing therapy was 0.54 (95% confidence interval [CI], 0.22–1.36), p = 0.194, while that for macrolide-free antimicrobials was 1.38 (95% CI, 0.57–3.34), p = 0.471. The adjusted hazard rate for mortality with low CD4 counts < 50 cells/mm3 was 2.79 (95%, 1.20–6.50), while that for unknown CD4 counts was 4.01 (95% CI, 1.17–13.77), compared to CD4 counts > 50 cells/mm3. Conclusions: Among HIV patients, NTM-PD predominated, and not disseminated disease. MAC-PD was the most common infection. Low CD4 counts was a significant risk factor for early death, while sex, NTM species, macrolide therapy, and previous TB were not.
Properties of Maxentropic DNA Synthesis Codes
Authors: Schouhamer Immink Kees , Weber Jos H. , Cai Kui
Published: November 2024

Low-weight codes have been proposed for efficiently synthesizing deoxyribonucleic acid (DNA) for massive data storage, where a multiple of DNA strands are synthesized in parallel. We report on the redundancy and information rate of maxentropic low-weight codes for asymptotically large codeword length. We compare the performance of low-complexity nibble replacement (NR) codes, which are designed to minimize the synthesis time, with the performance of maxentropic low-weight codes. Finally, the asymptotic redundancy and information rate of codes with a runlength limitation are investigated.
Bayesian Inference for Long Memory Stochastic Volatility Models
Authors: Chaim Pedro , Laurini Márcio Poletti
Published: November 2024

We explore the application of integrated nested Laplace approximations for the Bayesian estimation of stochastic volatility models characterized by long memory. The logarithmic variance persistence in these models is represented by a Fractional Gaussian Noise process, which we approximate as a linear combination of independent first-order autoregressive processes, lending itself to a Gaussian Markov Random Field representation. Our results from Monte Carlo experiments indicate that this approach exhibits small sample properties akin to those of Markov Chain Monte Carlo estimators. Additionally, it offers the advantages of reduced computational complexity and the mitigation of posterior convergence issues. We employ this methodology to estimate volatility dependency patterns for both the SP&500 index and major cryptocurrencies. We thoroughly assess the in-sample fit and extend our analysis to the construction of out-of-sample forecasts. Furthermore, we propose multi-factor extensions and apply this method to estimate volatility measurements from high-frequency data, underscoring its exceptional computational efficiency. Our simulation results demonstrate that the INLA methodology achieves comparable accuracy to traditional MCMC methods for estimating latent parameters and volatilities in LMSV models. The proposed model extensions show strong in-sample fit and out-of-sample forecast performance, highlighting the versatility of the INLA approach. This method is particularly advantageous in high-frequency contexts, where the computational demands of traditional posterior simulations are often prohibitive.