bluuebunny/crossref_metadata_2025 huggingface dataset:
Integration of Metabolomics and Transcriptomics to Explore Dynamic Alterations in Fruit Color and Quality in ‘Comte de Paris’ Pineapples during Ripening Processes
Authors: Song Kanghua , Zhang Xiumei , Liu Jiameng , Yao Quansheng , Li Yixing , Hou Xiaowan , Liu Shenghui , Qiu Xunxia , Yang Yue , Chen Li , Hong Keqian , Lin Lijing
Published: November 2023

Pineapple color yellowing and quality promotion gradually manifest as pineapple fruit ripening progresses. To understand the molecular mechanism underlying yellowing in pineapples during ripening, coupled with alterations in fruit quality, comprehensive metabolome and transcriptome investigations were carried out. These investigations were conducted using pulp samples collected at three distinct stages of maturity: young fruit (YF), mature fruit (MF), and fully mature fruit (FMF). This study revealed a noteworthy increase in the levels of total phenols and flavones, coupled with a concurrent decline in lignin and total acid contents as the fruit transitioned from YF to FMF. Furthermore, the analysis yielded 167 differentially accumulated metabolites (DAMs) and 2194 differentially expressed genes (DEGs). Integration analysis based on DAMs and DEGs revealed that the biosynthesis of plant secondary metabolites, particularly the flavonol, flavonoid, and phenypropanoid pathways, plays a pivotal role in fruit yellowing. Additionally, RNA-seq analysis showed that structural genes, such as FLS, FNS, F3H, DFR, ANR, and GST, in the flavonoid biosynthetic pathway were upregulated, whereas the COMT, CCR, and CAD genes involved in lignin metabolism were downregulated as fruit ripening progressed. APX as well as PPO, and ACO genes related to the organic acid accumulations were upregulated and downregulated, respectively. Importantly, a comprehensive regulatory network encompassing genes that contribute to the metabolism of flavones, flavonols, lignin, and organic acids was proposed. This network sheds light on the intricate processes that underlie fruit yellowing and quality alterations. These findings enhance our understanding of the regulatory pathways governing pineapple ripening and offer valuable scientific insight into the molecular breeding of pineapples.
Identification of CDK1, PBK, and CHEK1 as an Oncogenic Signature in Glioblastoma: A Bioinformatics Approach to Repurpose Dapagliflozin as a Therapeutic Agent
Authors: Chinyama Harold A. , Wei Li , Mokgautsi Ntlotlang , Lawal Bashir , Wu Alexander T. H. , Huang Hsu-Shan
Published: November 2023

Glioblastoma multiforme (GBM) is the most aggressive and lethal primary brain tumor whose median survival is less than 15 months. The current treatment regimen comprising surgical resectioning, chemotherapy with Temozolomide (TMZ), and adjuvant radiotherapy does not achieve total patient cure. Stem cells’ presence and GBM tumor heterogeneity increase their resistance to TMZ, hence the poor overall survival of patients. A dysregulated cell cycle in glioblastoma enhances the rapid progression of GBM by evading senescence or apoptosis through an over-expression of cyclin-dependent kinases and other protein kinases that are the cell cycle’s main regulatory proteins. Herein, we identified and validated the biomarker and predictive properties of a chemoradio-resistant oncogenic signature in GBM comprising CDK1, PBK, and CHEK1 through our comprehensive in silico analysis. We found that CDK1/PBK/CHEK1 overexpression drives the cell cycle, subsequently promoting GBM tumor progression. In addition, our Kaplan–Meier survival estimates validated the poor patient survival associated with an overexpression of these genes in GBM. We used in silico molecular docking to analyze and validate our objective to repurpose Dapagliflozin against CDK1/PBK/CHEK1. Our results showed that Dapagliflozin forms putative conventional hydrogen bonds with CDK1, PBK, and CHEK1 and arrests the cell cycle with the lowest energies as Abemaciclib.
The Role of Human and Animal Monocytes and Macrophages in Homeostasis and Disease
Authors: Kloc Malgorzata , Kubiak Jacek Z.
Published: November 2023

Monocytes and macrophages are the innate immune cells that are the first-line responders to invading pathogens or foreign objects[...]
Genetic Heterogeneity Underlying Phenotypes with Early-Onset Cerebellar Atrophy
Authors: Martínez-Rubio Dolores , Hinarejos Isabel , Argente-Escrig Herminia , Marco-Marín Clara , Lozano María Ana , Gorría-Redondo Nerea , Lupo Vincenzo , Martí-Carrera Itxaso , Miranda Concepción , Vázquez-López María , García-Pérez Asunción , Marco-Hernández Ana Victoria , Tomás-Vila Miguel , Aguilera-Albesa Sergio , Espinós Carmen
Published: November 2023

Cerebellar atrophy (CA) is a frequent neuroimaging finding in paediatric neurology, usually associated with cerebellar ataxia. The list of genes involved in hereditary forms of CA is continuously growing and reveals its genetic complexity. We investigated ten cases with early-onset cerebellar involvement with and without ataxia by exome sequencing or by a targeted panel with 363 genes involved in ataxia or spastic paraplegia. Novel variants were investigated by in silico or experimental approaches. Seven probands carry causative variants in well-known genes associated with CA or cerebellar hypoplasia: SETX, CACNA1G, CACNA1A, CLN6, CPLANE1, and TBCD. The remaining three cases deserve special attention; they harbour variants in MAST1, PI4KA and CLK2 genes. MAST1 is responsible for an ultrarare condition characterised by global developmental delay and cognitive decline; our index case added ataxia to the list of concomitant associated symptoms. PIK4A is mainly related to hypomyelinating leukodystrophy; our proband presented with pure spastic paraplegia and normal intellectual capacity. Finally, in a patient who suffers from mild ataxia with oculomotor apraxia, the de novo novel CLK2 c.1120T>C variant was found. The protein expression of the mutated protein was reduced, which may indicate instability that would affect its kinase activity.
Cellular Senescence: A Troy Horse in Pulmonary Fibrosis
Authors: Wan Ruyan , Wang Lan , Zhu Miaomiao , Li Wenwen , Duan Yudi , Yu Guoying
Published: November 2023

Pulmonary fibrosis (PF) is a chronic interstitial lung disease characterized by myofibroblast abnormal activation and extracellular matrix deposition. However, the pathogenesis of PF remains unclear, and treatment options are limited. Epidemiological studies have shown that the average age of PF patients is estimated to be over 65 years, and the incidence of the disease increases with age. Therefore, PF is considered an age-related disease. A preliminary study on PF patients demonstrated that the combination therapy of the anti-senescence drugs dasatinib and quercetin improved physical functional indicators. Given the global aging population and the role of cellular senescence in tissue and organ aging, understanding the impact of cellular senescence on PF is of growing interest. This article systematically summarizes the causes and signaling pathways of cellular senescence in PF. It also objectively analyzes the impact of senescence in AECs and fibroblasts on PF development. Furthermore, potential intervention methods targeting cellular senescence in PF treatment are discussed. This review not only provides a strong theoretical foundation for understanding and manipulating cellular senescence, developing new therapies to improve age-related diseases, and extending a healthy lifespan but also offers hope for reversing the toxicity caused by the massive accumulation of senescence cells in humans.
Discovery of New Anti-Cancer Agents against Patient-Derived Sorafenib-Resistant Papillary Thyroid Cancer
Authors: Kim Yuna , Yun Hyeok Jun , Choi Kyung Hwa , Kim Chan Wung , Lee Jae Ha , Weicker Raymond , Kim Seok-Mo , Park Ki Cheong
Published: November 2023

Thyroid cancer is the most well-known type of endocrine cancer that is easily treatable and can be completely cured in most cases. Nonetheless, anti-cancer drug-resistant metastasis or recurrence may occur and lead to the failure of cancer therapy, which eventually leads to the death of a patient with cancer. This study aimed to detect novel thyroid cancer target candidates based on validating and identifying one of many anti-cancer drug-resistant targets in patient-derived sorafenib-resistant papillary thyroid cancer (PTC). We focused on targeting the sarco/endoplasmic reticulum calcium ATPase (SERCA) in patient-derived sorafenib-resistant PTC cells compared with patient-derived sorafenib-sensitive PTC cells. We discovered novel SERCA inhibitors (candidates 33 and 36) by virtual screening. These candidates are novel SERCA inhibitors that lead to remarkable tumor shrinkage in a xenograft tumor model of sorafenib-resistant patient-derived PTC cells. These results are clinically valuable for the progression of novel combinatorial strategies that facultatively and efficiently target extremely malignant cancer cells, such as anti-cancer drug-resistant PTC cells.
Environmental Stimuli and Phytohormones in Anthocyanin Biosynthesis: A Comprehensive Review
Authors: Shi Lei , Li Xing , Fu Ying , Li Changjiang
Published: November 2023

Anthocyanin accumulation in plants plays important roles in plant growth and development, as well as the response to environmental stresses. Anthocyanins have antioxidant properties and play an important role in maintaining the reactive oxygen species (ROS) homeostasis in plant cells. Furthermore, anthocyanins also act as a “sunscreen”, reducing the damage caused by ultraviolet radiation under high-light conditions. The biosynthesis of anthocyanin in plants is mainly regulated by an MYB-bHLH-WD40 (MBW) complex. In recent years, many new regulators in different signals involved in anthocyanin biosynthesis were identified. This review focuses on the regulation network mediated by different environmental factors (such as light, salinity, drought, and cold stresses) and phytohormones (such as jasmonate, abscisic acid, salicylic acid, ethylene, brassinosteroid, strigolactone, cytokinin, and auxin). We also discuss the potential application value of anthocyanin in agriculture, horticulture, and the food industry.
A Putative Role for TRPC6 in Immune-Mediated Kidney Injury
Authors: ‘t Hart Daan C. , van der Vlag Johan , Nijenhuis Tom
Published: November 2023

Excessive activation of the immune system is the cause of a wide variety of renal diseases. However, the pathogenic mechanisms underlying the aberrant activation of the immune system in the kidneys often remain unknown. TRPC6, a member of the Ca2+-permeant family of TRPC channels, is important in glomerular epithelial cells or podocytes for the process of glomerular filtration. In addition, TRPC6 plays a crucial role in the development of kidney injuries by inducing podocyte injury. However, an increasing number of studies suggest that TRPC6 is also responsible for tightly regulating the immune cell functions. It remains elusive whether the role of TRPC6 in the immune system and the pathogenesis of renal inflammation are intertwined. In this review, we present an overview of the current knowledge of how TRPC6 coordinates the immune cell functions and propose the hypothesis that TRPC6 might play a pivotal role in the development of kidney injury via its role in the immune system.
An Approach for Risk Traceability Using Blockchain Technology for Tracking, Tracing, and Authenticating Food Products
Authors: Sugandh Urvashi , Nigam Swati , Khari Manju , Misra Sanjay
Published: November 2023

Regulatory authorities, consumers, and producers alike are alarmed by the issue of food safety, which is a matter of international concern. The conventional approaches utilized in food quality management demonstrate deficiencies in their capacity to sufficiently address issues related to traceability, transparency, and accountability. The emergence of blockchain technology (BCT) has provided a feasible approach to tackle the challenge of regulating food safety. This research paper presents a methodology for implementing blockchain technology to establish risk traceability in the context of monitoring, tracing, and authenticating agricultural products. The proposed system underwent a comprehensive evaluation, which placed significant emphasis on simulation parameters and assessment standards. The aim of the study was to demonstrate the effectiveness of the system through the assessment of various quantitative metrics, including throughput, latency, and resource utilization. The Hyperledger Fabric and Hyperledger Caliper were employed in the formulation and assessment of algorithms intended for agricultural supply chain management. The configuration comprising two entities and two peers achieved the highest write throughput (205.87 transactions per second; TPS), thereby demonstrating the network’s effective transaction processing capability. In a two-organization, two-peer system, the mean latency for read operations exhibited variability spanning from 0.037 to 0.061 s, contingent upon the transaction rates and accounting for the duration needed for network processing and validation. The results were visually depicted, offering a distinct demonstration of the system’s efficacy under various conditions. This study presents a quantitative analysis that illustrates the efficacy of the blockchain system in enhancing the traceability of agricultural products across the entire supply chain. The results of this research suggest that the implementation of blockchain technology could potentially enhance both the security and efficacy of food supply management.
Effects of the Weather on the Seasonal Population Trend of Aedes albopictus (Diptera: Culicidae) in Northern Italy
Authors: Carrieri Marco , Albieri Alessandro , Angelini Paola , Soracase Monica , Dottori Michele , Antolini Gabriele , Bellini Romeo
Published: November 2023

Background: Aedes albopictus, the Asian tiger mosquito, has become a prevalent pest in Italy, causing severe nuisance and posing a threat of transmission of arboviruses introduced by infected travelers. In this study, we investigated the influence of weather parameters on the seasonal population density of Aedes albopictus. Methods: A Bayesian approach was employed to identify the best meteorological predictors of species trend, using the eggs collected monthly from 2010 to 2022 by the Emilia-Romagna regional monitoring network. Results: The findings show that the winter–spring period (January to May) plays a crucial role in the size of the first generation and seasonal development of the species. Conclusions: A temperate winter and a dry and cold March, followed by a rainy and hot spring and a rainy July, seem to favor the seasonal development of Ae. albopictus.
Novel Microsatellite Loci, Cross-Species Validation of Multiplex Assays, and By-Catch Mitochondrial Genomes on Ochthebius Beetles from Supratidal Rockpools
Authors: García-Meseguer Antonio José , Villastrigo Adrián , Mirón-Gatón Juana María , Millán Andrés , Velasco Josefa , Muñoz Irene
Published: November 2023

Here we focus on designing, for the first time, microsatellite markers for evolutionary and ecological research on aquatic beetles from the genus Ochthebius (Coleoptera, Hydraenidae). Some of these non-model species, with high cryptic diversity, exclusively inhabit supratidal rockpools, extreme and highly dynamic habitats with important anthropogenic threats. We analysed 15 individuals of four species (O. lejolisii, O. subinteger, O. celatus, and O. quadricollis) across 10 localities from the Mediterranean coasts of Spain and Malta. Using next-generation sequencing technology, two libraries were constructed to interpret the species of the two subgenera present consistently (Ochthebius s. str., O. quadricollis; and Cobalius, the rest of the species). Finally, 20 markers (10 for each subgenus) were obtained and successfully tested by cross-validation in the four species under study. As a by-catch, we could retrieve the complete mitochondrial genomes of O. lejolisii, O. quadricollis, and O. subinteger. Interestingly, the mitochondrial genome of O. quadricollis exhibited high genetic variability compared to already published data. The novel SSR panels and mitochondrial genomes for Ochthebius will be valuable in future research on species identification, diversity, genetic structure, and population connectivity in highly dynamic and threatened habitats such as supratidal coastal rockpools.
The Influence of Individualized Three-Dimensional Holographic Models on Patients’ Knowledge Qualified for Intervention in the Treatment of Peripheral Arterial Disease (PAD)
Authors: Skórka Patryk , Kargul Michał , Seemannová Diana , Gajek Bartosz , Gutowski Piotr , Kazimierczak Arkadiusz , Rynio Paweł
Published: November 2023

We sought to determine the role of the patient-specific, three-dimensional (3D) holographic vascular model in patient medical knowledge and its influence on obtaining a more conscious informed consent process for percutaneous balloon angioplasty (PTA). Patients with peripheral arterial disease who had been scheduled for PTA were enrolled in the study. Information regarding the primary disease, planned procedure, and informed consent was recorded in typical fashion. Subsequently, the disease and procedure details were presented to the patient, showing the patients their individual model. A patient and medical supervisor equipped with mixed reality headsets could both simultaneously manipulate the hologram using gestures. The holographic 3D model had been created on a scale of 1:1 based on computed tomography scans. The patient’s knowledge was tested by the completion of a questionnaire before and after the interaction in a mixed reality environment. Seventy-nine patients manipulated arterial holograms in mixed reality head-mounted devices. Before the 3D holographic artery model interaction, the mean ± standard deviation score of the knowledge test was 2.95 ± 1.21 points. After the presentation, the score had increased to 4.39 ± 0.82, with a statistically significant difference (p = 0.0000) between the two scores. Using a Likert scale from 1 to 5, the patients had scored the use of the 3D holographic model at 3.90 points regarding its usefulness in comprehending their medical condition; at 4.04 points regarding the evaluation of the holograms as helpful in understanding the course of surgery; and rated the model at 1.99 points in reducing procedure-related stress. Using a nominal scale (know or don’t know), the patients had self-assessed their knowledge of the procedure before and after the 3D model presentation, with a score of 6.29 ± 2.01 and 8.39 ± 1.54, respectively. The study group tolerated the use of head-mounted devices. Only one patient had nausea and dizziness, while four patients experienced transient eye pain. The 3D holographic arterial model aided in the understanding of patients’ knowledge regarding the disease and procedure, making the informed consent process more conscious. The holograms improved the patient’s self-consciousness. Mixed reality headset-related complications were rare and within acceptable rates.
The Ketogenic Effect of SGLT-2 Inhibitors—Beneficial or Harmful?
Authors: Koutentakis Michail , Kuciński Jakub , Świeczkowski Damian , Surma Stanisław , Filipiak Krzysztof J. , Gąsecka Aleksandra
Published: November 2023

Sodium–glucose cotransporter-2 (SGLT-2) inhibitors, also called gliflozins or flozins, are a class of drugs that have been increasingly used in the management of type 2 diabetes mellitus (T2DM) due to their glucose-lowering, cardiovascular (CV), and renal positive effects. However, recent studies suggest that SGLT-2 inhibitors might also have a ketogenic effect, increasing ketone body production. While this can be beneficial for some patients, it may also result in several potential unfavorable effects, such as decreased bone mineral density, infections, and ketoacidosis, among others. Due to the intricate and multifaceted impact caused by SGLT-2 inhibitors, this initially anti-diabetic class of medications has been effectively used to treat both patients with chronic kidney disease (CKD) and those with heart failure (HF). Additionally, their therapeutic potential appears to extend beyond the currently investigated conditions. The objective of this review article is to present a thorough summary of the latest research on the mechanism of action of SGLT-2 inhibitors, their ketogenesis, and their potential synergy with the ketogenic diet for managing diabetes. The article particularly discusses the benefits and risks of combining SGLT-2 inhibitors with the ketogenic diet and their clinical applications and compares them with other anti-diabetic agents in terms of ketogenic effects. It also explores future directions regarding the ketogenic effects of SGLT-2 inhibitors.
Severe Parainfluenza Viral Infection—A Retrospective Study of Adult Intensive Care Patients
Authors: Watson Adam , Beecham Ryan , Grocott Michael P. W. , Saeed Kordo , Dushianthan Ahilanandan
Published: November 2023

There is little known about parainfluenza virus (PIV) infection in adult intensive care unit (ICU) patients. Here, we aim to describe the characteristics, clinical course and outcomes of PIV infection in adults requiring intensive care. In this retrospective study of consecutive patients admitted to our ICU with confirmed PIV infection over a 7-year period, we report the patient characteristics, laboratory tests and prognostic scores on ICU admission. The main outcomes reported are 30-day mortality and organ support required. We included 50 patients (52% male, mean age 67.6 years). The mean PaO2/FiO2 and neutrophil/lymphocyte ratios on ICU admission were 198 ± 82 mmHg and 15.7 ± 12.5. Overall, 98% of patients required respiratory support and 24% required cardiovascular support. The median length of ICU stay was 5.9 days (IQR 3.7–9.1) with a 30-day mortality of 40%. In conclusion, PIV infection in adult ICU patients is associated with significant mortality and morbidity. There were significant differences between patients who presented with primary hypoxemic respiratory failure and hypercapnic respiratory failure.
Drug–Drug Interactions Involving Dexamethasone in Clinical Practice: Myth or Reality?
Authors: Bourdin Venceslas , Bigot William , Vanjak Anthony , Burlacu Ruxandra , Lopes Amanda , Champion Karine , Depond Audrey , Amador-Borrero Blanca , Sene Damien , Comarmond Chloe , Mouly Stéphane
Published: November 2023

Concomitant administration of multiple drugs frequently causes severe pharmacokinetic or pharmacodynamic drug–drug interactions (DDIs) resulting in the possibility of enhanced toxicity and/or treatment failure. The activity of cytochrome P450 (CYP) 3A4 and P-glycoprotein (P-gp), a drug efflux pump sharing localization and substrate affinities with CYP3A4, is a critical determinant of drug clearance, interindividual variability in drug disposition and clinical efficacy, and appears to be involved in the mechanism of numerous clinically relevant DDIs, including those involving dexamethasone. The recent increase in the use of high doses of dexamethasone during the COVID-19 pandemic have emphasized the need for better knowledge of the clinical significance of drug–drug interactions involving dexamethasone in the clinical setting. We therefore aimed to review the already published evidence for various DDIs involving dexamethasone in vitro in cell culture systems and in vivo in animal models and humans.
Outcomes of Laparoscopic Surgery in Very Elderly Patients with Colorectal Cancer: A Survival Analysis and Comparative Study
Authors: Passuello Nicola , Polese Lino , Ometto Giulia , Grossi Ugo , Mammano Enzo , Vittadello Fabrizio , Frasson Alvise , Tessari Emanuela , Bartolotta Patrizia , Gregori Dario , Sarzo Giacomo
Published: November 2023

(1) Background: Colorectal cancer (CRC) is a global health concern, particularly among the elderly population. This study aimed to assess the impact of laparoscopic surgery on CRC patients aged ≥80 years. (2) Methods: We conducted a retrospective analysis of prospectively collected data from consecutive CRC patients who underwent surgery at our institution between July 2018 and July 2023. The patients were categorized into three groups: those aged over 80 who underwent laparoscopic surgery (Group A), those aged over 80 who underwent open surgery (Group B), and those under 80 who underwent laparoscopic surgery (Group C). We examined various clinical and surgical parameters, including demographic data, medical history, surgical outcomes, and survival. (3) Results: Group A (N = 113) had shorter hospital stays than Group B (N = 23; p = 0.042), with no significant differences in complications or 30-day outcomes. Compared to Group C (N = 269), Group A had higher comorbidity indices (p < 0.001), more emergency admissions, anemia, low hemoglobin levels, colonic obstruction (p < 0.001), longer hospital stays (p < 0.001), and more medical complications (p = 0.003). Laparotomic conversion was associated with obstructive neoplasms (p < 0.001), and medical complications with ASA scores (p < 0.001). Both the medical and surgical complications predicted adverse 30-day outcomes (p = 0.007 and p < 0.001). Survival analysis revealed superior overall survival (OS) in Group A vs. Group B (p < 0.0001) and inferior OS vs. Group C (p < 0.0001). After a landmark analysis, the OS for patients aged 80 or older and those under 80 appeared to be similar (HR 2.55 [0.75–8.72], p = 0.136). (4) Conclusions: Laparoscopic surgery in very elderly CRC patients shows comparable oncological outcomes and surgical complications to younger populations. Survival benefits are influenced by age, comorbidities, and medical complications. Further prospective multicenter studies are needed in order to validate these findings.
Spontaneous Cultural Conversion Rate of Mycobacterium avium Complex Pulmonary Disease Based on BACES Severity
Authors: Kim Bo-Guen , Yu Jin Young , Jhun Byung Woo
Published: November 2023

Background: Only a few clinical factors can aid in predicting spontaneous culture conversion (SCC) in patients with Mycobacterium avium complex-pulmonary disease (MAC-PD). In this study, we aimed to evaluate whether the rate of SCC varies according to the severity of the disease in MAC-PD patients. Methods: We retrospectively classified 373 MAC-PD patients who had undergone watchful waiting without antibiotics based on the severity assessment using the ‘body mass index (BMI), age, cavity, erythrocyte sedimentation rate (ESR), and sex (BACES)’ criteria. We evaluated the rate of SCC in MAC-PD patients based on BACES severity and analyzed the relevant factors. Results: Of 373 patients, 153 (41%) achieved SCC without antibiotics during a median follow-up of 48.1 months. There was a trend toward a higher SCC rate in patients with lower BACES severity: 48% (87/183), 37% (58/157), and 24% (8/33) in the mild, moderate, and severe BACES groups, respectively. In addition, a favorable outcome, defined as maintaining SCC or having two consecutive negative sputum cultures until the last follow-up date, was also more common in patients with lower BACES severities of 53% (97/183), 34% (54/157), and 18% (6/33) in the mild, moderate, and severe BACES groups, respectively. In multivariate analysis, moderate BACES (hazard ratio [HR] = 0.63; 95% confidence interval [CI] 0.44–0.91; p = 0.013) and severe BACES (HR 0.37; 95% CI 0.16–0.90; p = 0.028) had a significantly negative impact on favorable outcomes compared to mild BACES. Conclusions: Lower BACES severity may be associated with SCC in MAC-PD patients.
Atrial Strain Assessment for the Early Detection of Cancer Therapy-Related Cardiac Dysfunction in Breast Cancer Women (The STRANO STUDY: Atrial Strain in Cardio-Oncology)
Authors: Di Lisi Daniela , Moreo Antonella , Casavecchia Grazia , Cadeddu Dessalvi Christian , Bergamini Corinna , Zito Concetta , Madaudo Cristina , Madonna Rosalinda , Cameli Matteo , Novo Giuseppina
Published: November 2023

Left ventricular global longitudinal strain (GLS) has an important role in the diagnosis of cancer therapy-related cardiac dysfunction (CTRCD). Little is known about the role of atrial function in diagnosing CTRCD. The aim of our study was to assess the impact of anti-cancer drugs on atrial function measured by speckle-tracking echocardiography in breast cancer women. A prospective multicenter study was conducted enrolling 169 breast cancer women treated with anthracyclines. A cardiological evaluation including an electrocardiogram and echocardiogram with an analysis of GLS, left atrial (LA) strain, and LA stiffness (LASi) was performed at baseline (T0), 3 (T1), and 6 months (T2) after starting chemotherapy. The patients were divided into two groups: patients with asymptomatic mild cardiotoxicity at T1 (with a relative reduction in GLS > 15%; Group 1) and those without (Group 2). We did not find a significant change in left ventricular ejection fraction (LVEF) at T1 and T2; we found a significant change in GLS (p-value < 0.0001) in the peak atrial longitudinal strain (PALS) and in LASi (p-value < 0.0001). Impairment of atrial function was greater in Group 1 compared to Group 2. A PALS variation > 20.8% identified patients who were most likely to develop asymptomatic mild cardiotoxicity [AUC 0.62; CI (0.51–0.73) p = 0.06, sensitivity 45%, specificity 69.5%]. Conclusions: PALS and LASi significantly change during chemotherapy in association with GLS. Atrial strain is an additional parameter that could be measured together with GLS to detect cardiotoxicity early.
PSMA PET/CT in Castration-Resistant Prostate Cancer: Myth or Reality?
Authors: Urso Luca , Filippi Luca , Castello Angelo , Marzola Maria Cristina , Bartolomei Mirco , Cittanti Corrado , Florimonte Luigia , Castellani Massimo , Zucali Paolo , Bruni Alessio , Sabbatini Roberto , Dominici Massimo , Panareo Stefano , Evangelista Laura
Published: November 2023

Background: prostate-specific membrane antigen (PSMA) ligand PET has been recently incorporated into international guidelines for several different indications in prostate cancer (PCa) patients. However, there are still some open questions regarding the role of PSMA ligand PET in castration-resistant prostate cancer (CRPC). The aim of this work is to assess the clinical value of PSMA ligand PET/CT in patients with CRPC. Results: PSMA ligand PET has demonstrated higher detection rates in comparison to conventional imaging and allows for a significant reduction in the number of M0 CRPC patients. However, its real impact on patients’ prognosis is still an open question. Moreover, in CRPC patients, PSMA ligand PET presents some sensitivity and specificity limitations. Due to its heterogeneity, CRPC may present a mosaic of neoplastic clones, some of which could be PSMA−/FDG+, or vice versa. Likewise, unspecific bone uptake (UBU) and second primary neoplasms (SNPs) overexpressing PSMA in the neoangiogenic vessels represent potential specificity issues. Integrated multi-tracer imaging (PSMA ligand and [18F]FDG PET) together with a multidisciplinary discussion could allow for reaching the most accurate evaluation of each patient from a precision medicine point of view.
Drug Clearance in Patients with Inflammatory Bowel Disease Treated with Biologics
Authors: Deyhim Tina , Cheifetz Adam S. , Papamichael Konstantinos
Published: November 2023

Biological therapy is very effective for treating patients with moderate to severe inflammatory bowel disease (IBD). However, up to 40% can have primary non-response, and up to 50% of the patients can experience a loss of response to anti-tumor necrosis factor therapy. These undesirable outcomes can be attributed to either a mechanistic failure or pharmacokinetic (PK) issues characterized by an inadequate drug exposure and a high drug clearance. There are several factors associated with accelerated clearance of biologics including increased body weight, low serum albumin and immunogenicity. Drug clearance has gained a lot of attention recently as cumulative data suggest that there is an association between drug clearance and therapeutic outcomes in patients with IBD. Moreover, clearance is used by model informed precision dosing (MIDP) tools, or PK dashboards, to adjust the dosing for reaching a target drug concentration threshold towards a more personalized application of TDM. However, the role of drug clearance in clinical practice is yet to be determined. This comprehensive review aims to present data regarding the variables affecting the clearance of specific biologics, the association of clearance with therapeutic outcomes and the role of clearance monitoring and MIPD in patients with IBD.
Genome-Wide Informative Microsatellite Markers and Population Structure of Fusarium virguliforme from Argentina and the USA
Authors: Silva Leandro Lopes da , Tian Huan , Schemerhorn Brandi , Xu Jin-Rong , Cai Guohong
Published: November 2023

Soybean sudden death syndrome (SDS) is a destructive disease that causes substantial yield losses in South and North America. Whereas four Fusarium species were identified as the causal agents, F. virguliforme is the primary SDS-causing pathogen in North America and it also contributes substantially to SDS in Argentina. In this study, we comparatively analyzed genome assemblies of four F. virguliforme strains and identified 29 informative microsatellite markers. Sixteen of the 29 markers were used to investigate the genetic diversity and population structure of this pathogen in a collection of 90 strains from Argentina and the USA. A total of 37 multilocus genotypes (MLGs) were identified, including 10 MLGs in Argentina and 26 in the USA. Only MLG2, the most dominant MLG, was found in both countries. Analyses with three different approaches showed that these MLGs could be grouped into three clusters. Cluster IA consisting of four MLGs exclusively from the USA has much higher genetic diversity than the other two clusters, suggesting that it may be the ancestral cluster although additional data are necessary to support this hypothesis. Clusters IB and II consisted of 13 and 21 MLGs, respectively. MLGs belonging to these two clusters were present in all four sampled states in Argentina and all five sampled states in the USA.
Investigation of Web-Based Eye-Tracking System Performance under Different Lighting Conditions for Neuromarketing
Authors: Yüksel Doğuş
Published: November 2023

The increasing popularity of neuromarketing has led to the emergence of various measurement methods, such as webcam-based eye-tracking technology. Webcam-based eye-tracking technology is noteworthy not only for its use in laboratories but also for its ability to be applied to participants online in their natural environments through a link. However, the complexity of e-commerce interfaces necessitates high performance in eye-tracking methods. This complexity and the applicability of webcam-based eye-tracking technology in various environments have raised research questions about how its performance changes depending on the type and location of lighting. To answer these questions, experiments were conducted with 30 users in two different experimental environments illuminated by artificial and natural methods, with the lighting from the left, right, and front. Participants were asked to focus on targets located in specially prepared graphics for the experiment. In the heatmaps obtained in the eye-tracking tests, the distance and angular difference between the focal point and the target point were measured using the polar coordinate system. The findings indicate that measurements taken with lighting coming from the center were more efficient in both natural and artificial lighting types and measurements taken under natural lighting performed 24% better than artificial ones. Web camera-based eye-tracking technology is a promising method. However, detailed statistical analyses have demonstrated that for complex interfaces like e-commerce, the position and type of lighting are crucial parameters.
Adiponectin: A Promising Target for the Treatment of Diabetes and Its Complications
Authors: Begum Mahmuda , Choubey Mayank , Tirumalasetty Munichandra Babu , Arbee Shahida , Mohib Mohammad Mohabbulla , Wahiduzzaman Md , Mamun Mohammed A. , Uddin Mohammad Borhan , Mohiuddin Mohammad Sarif
Published: November 2023

Diabetes mellitus, a chronic metabolic disorder characterized by hyperglycemia, presents a formidable global health challenge with its associated complications. Adiponectin, an adipocyte-derived hormone, has emerged as a significant player in glucose metabolism and insulin sensitivity. Beyond its metabolic effects, adiponectin exerts anti-inflammatory, anti-oxidative, and vasoprotective properties, making it an appealing therapeutic target for mitigating diabetic complications. The molecular mechanisms by which adiponectin impacts critical pathways implicated in diabetic nephropathy, retinopathy, neuropathy, and cardiovascular problems are thoroughly examined in this study. In addition, we explore possible treatment options for increasing adiponectin levels or improving its downstream signaling. The multifaceted protective roles of adiponectin in diabetic complications suggest its potential as a novel therapeutic avenue. However, further translational studies and clinical trials are warranted to fully harness the therapeutic potential of adiponectin in the management of diabetic complications. This review highlights adiponectin as a promising target for the treatment of diverse diabetic complications and encourages continued research in this pivotal area of diabetes therapeutics.
Comparison of Machining Performance of Ti-6Al-4V under Dry and Cryogenic Techniques Based on Tool Wear, Surface Roughness, and Power Consumption
Authors: Chauhan Dhvanil , Makhesana Mayur A. , Rahman Rashid Rizwan Abdul , Joshi Vivek , Khanna Navneet
Published: November 2023

The machining of Ti-6Al-4V alloys is challenging due to their high strength, poor thermal conductivity, and high chemical reactivity. When used in traditional machining, cryogenic coolants can reduce tool wear, thus extending tool life, improving surface finish, and requiring less power with reduced environmental effects. In this context, this study aimed to perform a machinability analysis of the surface roughness, power consumption, tool wear, and specific energy consumption of a Ti-6Al-4V titanium alloy and to comprehend the performance of dry and cryogenic machining in turning operations. A comprehensive analysis of tool wear and specific cutting energy (SCE) under dry and cryogenic machining was conducted. It was found that the machining time under a cryogenic environment was increased by 83% and 39% at 80 and 90 m/min compared to a cutting speed at 100 m/min. The higher cutting speed (100 m/min) in cryogenic environments produced an improved surface finish. Compared to dry machining, the cooling effect of liquid CO2 helped dissipate heat and reduce thermal damage, improving surface finish. The findings revealed that in dry conditions, approximately 5.55%, 26.45%, and 27.61% less power was consumed than in cryogenic conditions at 80, 90, and 100 m/min cutting speeds, respectively. Based on the outcomes of the work, the application of cryogenic cooling can be considered an alternative to dry and flood cooling for improving the machinability of Ti-6Al-4V alloys.
Bearing Capacity Performance and Optimal Design of a Novel Aluminum Alloy Arch Gusset Joint
Authors: Wang Huaihao , Guo Rongxin , Zhang Yubo , Yang Yang , Xiao Weirong
Published: November 2023

Current research on aluminum alloy gusset joints has neglected the influences of the angle between members and the curvature of the joint plate on joint performance. This study introduces the concept of the planar angle and establishes 16 joint models using ABAQUS finite element software with parameters such as the planar angle, arch angles, joint plate thickness, web thickness, and flange thickness. The load-bearing capacity of the novel aluminum alloy arch gusset joint is theoretically analyzed, and the concepts of strong and weak axes are proposed. The failure modes and significance of different parameters regarding the bearing capacity and initial stiffness of the joint under various parameters are summarized. The results indicate that the planar and arch angles significantly affect the bearing capacity, stiffness, and failure mode of the joint.
Characterizing and Modeling Transformation-Induced Plasticity in 13Cr-4Ni Welds upon Cooling
Authors: Lévesque Jean-Benoit , Baillargeon Carlo , Paquet Daniel , Lanteigne Jacques , Champliaud Henri
Published: November 2023

Dilatometric experiments were conducted with the main purpose of measuring the transformation-induced coefficients of 13% chromium and 4% nickel, which are martensitic stainless steel base and filler materials used for hydraulic turbine manufacturing. To this end, a set of experiments was conducted in a quenching dilatometer equipped with loading capabilities. The measurement system was further improved by means of modified pushrods to allow for the use of specimens with geometries that are compliant with tensile test standards. This improvement allowed for the measurement of the materials’ phases and respective yield strengths. The dataset was further used to determine the relationship between the applied external stress and the martensitic start temperature (Ms) upon cooling. The TRIP coefficient’s K values for both the S41500 steel and E410NiMo filler material were measured at 8.12×10−5 and 7.11×10−5, respectively. Additionally, the solid phase transformation model parameters for both the austenitic and martensitic transformation of the filler material were measured. These parameters were then used to model austenitic-phase-transformation kinetics and martensite transformation, including transformation-induced plasticity effects. Good agreement was achieved between the calculation and the experiments.
Research on the Mechanical Model and Hysteresis Performance of a New Mild Steel-Rotational Friction Hybrid Self-Centering Damper
Authors: Wang Debin , Pang Ran , Wang Gang , Fan Guoxi
Published: November 2023

A mild steel-friction self-centering damper with a hybrid energy-dissipation mechanism (MS-SCFD) was proposed, which consisted of a mild steel, frictional, dual-energy-dissipation system and a disc spring resetting system. The structure and principle of the MS-SCFD were explained in detail while the restoring force model was established. The hysteretic behavior of the MS-SCFD under low-cycle reciprocating loading was modeled. Then, the influence of parameters such as the disc spring preload, the friction coefficient, and the soft-steel thickness on the mechanical properties of the MS-SCFD was investigated. The results indicate that the simulation results are basically consistent with the theoretical prediction results, with a maximum error of only 9.46% for the key points of bearing capacity. Since the MS-SCFD is provided with a hysteretic curve in the typical flag type, it will obtain the capacity of excellent self-centering performance. It can effectively enhance the stiffness, bearing capacity, and self-centering capability of the damper after the pre-pressure of the disc spring is increased. The energy-dissipation capacity of the MS-SCFD increases with the increase in the friction coefficient. However, it also increases the residual deformation of the MS-SCFD. The energy dissipation of the MS-SCFD is particularly sensitive to the thickness of mild steel. After being loaded, all components of the MS-SCFD are not damaged except for the plastic deformation caused by the yielding of the mild steel. The normal function of the MS-SCFD can be restored simply by replacing the mild steel plates after the earthquake. Therefore, it can significantly enhance the economy and applicability of the damper.
Machine Learning Algorithms for Predicting Mechanical Stiffness of Lattice Structure-Based Polymer Foam
Authors: Hooshmand Mohammad Javad , Sakib-Uz-Zaman Chowdhury , Khondoker Mohammad Abu Hasan
Published: November 2023

Polymer foams are extensively utilized because of their superior mechanical and energy-absorbing capabilities; however, foam materials of consistent geometry are difficult to produce because of their random microstructure and stochastic nature. Alternatively, lattice structures provide greater design freedom to achieve desired material properties by replicating mesoscale unit cells. Such complex lattice structures can only be manufactured effectively by additive manufacturing or 3D printing. The mechanical properties of lattice parts are greatly influenced by the lattice parameters that define the lattice geometries. To study the effect of lattice parameters on the mechanical stiffness of lattice parts, 360 lattice parts were designed by varying five lattice parameters, namely, lattice type, cell length along the X, Y, and Z axes, and cell wall thickness. Computational analyses were performed by applying the same loading condition on these lattice parts and recording corresponding strain deformations. To effectively capture the correlation between these lattice parameters and parts’ stiffness, five machine learning (ML) algorithms were compared. These are Linear Regression (LR), Polynomial Regression (PR), Decision Tree (DT), Random Forest (RF), and Artificial Neural Network (ANN). Using evaluation metrics such as mean squared error (MSE), root mean squared error (RMSE), and mean absolute error (MAE), all ML algorithms exhibited significantly low prediction errors during the training and testing phases; however, the Taylor diagram demonstrated that ANN surpassed other algorithms, with a correlation coefficient of 0.93. That finding was further supported by the relative error box plot and by comparing actual vs. predicted values plots. This study revealed the accurate prediction of the mechanical stiffness of lattice parts for the desired set of lattice parameters.
A Yield Stress and Work Hardening Model of Al-Mg-Si Alloy Considering the Strengthening Effect of β” and β’ Precipitates
Authors: Zheng Xiaoyu , Huang Qi , Mao Hong , Li Kai , Xiao Namin , Li Xingwu , Du Yong , Liu Yuling , Kong Yi
Published: November 2023

Precipitates are the primary source of strength for the Al-Mg-Si alloy. Aluminum alloy in the peak-aged state mainly contains β” and β’ precipitates. Most of the literature has only considered the strengthening effect of β”. Here, we develop a single-crystal intensity model including both precipitate enhancement effects for the first time. This model was subsequently implemented into a crystal plastic finite-element method to model the uniaxial tensile process of a polycrystalline aggregate model of Al-Mg-Si alloy. The simulation results for uniaxial stretching are in good agreement with the experimental results, confirming that the constitutive parameters used for the single-crystal strength model with two precipitates are based on realistic physical implications. Furthermore, by comparing the uniaxial tensile simulation results of a peak-aged alloy considering the actual precipitated phase composition of the alloy with those assuming that the precipitated phase is only the β” phase, the predicted tensile strength of the former is around 5.65% lower than that of the latter, suggesting that the two kinds of precipitation should be separately considered when simulating the mechanical response of Al-Mg-Si alloy. It is highly expected that the present simulation strategy is not limited to Al-Mg-Si alloys, and it can be equally applied to the other age-enhanced alloys.