bluuebunny/crossref_metadata_2025 huggingface dataset:
Reviewing the Structure–Function Paradigm in Polyglutamine Disorders: A Synergistic Perspective on Theoretical and Experimental Approaches
Authors: Moldovean-Cioroianu Nastasia Sanda
Published: June 2024

Polyglutamine (polyQ) disorders are a group of neurodegenerative diseases characterized by the excessive expansion of CAG (cytosine, adenine, guanine) repeats within host proteins. The quest to unravel the complex diseases mechanism has led researchers to adopt both theoretical and experimental methods, each offering unique insights into the underlying pathogenesis. This review emphasizes the significance of combining multiple approaches in the study of polyQ disorders, focusing on the structure–function correlations and the relevance of polyQ-related protein dynamics in neurodegeneration. By integrating computational/theoretical predictions with experimental observations, one can establish robust structure–function correlations, aiding in the identification of key molecular targets for therapeutic interventions. PolyQ proteins’ dynamics, influenced by their length and interactions with other molecular partners, play a pivotal role in the polyQ-related pathogenic cascade. Moreover, conformational dynamics of polyQ proteins can trigger aggregation, leading to toxic assembles that hinder proper cellular homeostasis. Understanding these intricacies offers new avenues for therapeutic strategies by fine-tuning polyQ kinetics, in order to prevent and control disease progression. Last but not least, this review highlights the importance of integrating multidisciplinary efforts to advancing research in this field, bringing us closer to the ultimate goal of finding effective treatments against polyQ disorders.
Melatonin: The Multifaceted Molecule in Plant Growth and Defense
Authors: Khan Murtaza , Hussain Adil , Yun Byung-Wook , Mun Bong-Gyu
Published: June 2024

Melatonin (MEL), a hormone primarily known for its role in regulating sleep and circadian rhythms in animals, has emerged as a multifaceted molecule in plants. Recent research has shed light on its diverse functions in plant growth and defense mechanisms. This review explores the intricate roles of MEL in plant growth and defense responses. MEL is involved in plant growth owing to its influence on hormone regulation. MEL promotes root elongation and lateral root formation and enhances photosynthesis, thereby promoting overall plant growth and productivity. Additionally, MEL is implicated in regulating the circadian rhythm of plants, affecting key physiological processes that influence plant growth patterns. MEL also exhibits antioxidant properties and scavenges reactive oxygen species, thereby mitigating oxidative stress. Furthermore, it activates defense pathways against various biotic stressors. MEL also enhances the production of secondary metabolites that contribute to plant resistance against environmental changes. MEL’s ability to modulate plant response to abiotic stresses has also been extensively studied. It regulates stomatal closure, conserves water, and enhances stress tolerance by activating stress-responsive genes and modulating signaling pathways. Moreover, MEL and nitric oxide cooperate in stress responses, antioxidant defense, and plant growth. Understanding the mechanisms underlying MEL’s actions in plants will provide new insights into the development of innovative strategies for enhancing crop productivity, improving stress tolerance, and combating plant diseases. Further research in this area will deepen our knowledge of MEL’s intricate functions and its potential applications in sustainable agriculture.
Synthesis, Molecular Electron Density Theory Study, Molecular Docking, and Pharmacological Evaluation of New Coumarin–Sulfonamide–Nitroindazolyl–Triazole Hybrids as Monoamine Oxidase Inhibitors
Authors: Eddahmi Mohammed , La Spada Gabriella , Domingo Luis R. , Vergoten Gérard , Bailly Christian , Catto Marco , Bouissane Latifa
Published: June 2024

Inhibitors of monoamine oxidases (MAOs) are of interest for the treatment of neurodegenerative disorders and other human pathologies. In this frame, the present work describes different synthetic strategies to obtain MAO inhibitors via the coupling of the aminocoumarin core with arylsulfonyl chlorides followed by copper azide-alkyne cycloaddition, leading to coumarin–sulfonamide–nitroindazolyl–triazole hybrids. The nitration position on the coumarin moiety was confirmed through nuclear magnetic resonance spectroscopy and molecular electron density theory in order to elucidate the molecular mechanism and selectivity of the electrophilic aromatic substitution reaction. The coumarin derivatives were evaluated for their inhibitory potency against monoamine oxidases and cholinesterases. Molecular docking calculations provided a rational binding mode of the best compounds in the series with MAO A and B. The work identified hybrids 14a–c as novel MAO inhibitors, with a selective action against isoform B, of potential interest to combat neurological diseases.
Accelerated Electron Ionization-Induced Changes in the Myenteric Plexus of the Rat Stomach
Authors: Ardasheva Raina , Popov Veselin , Yotov Viktor , Prissadova Natalia , Pencheva Mina , Slavova Iva , Turiyski Valentin , Krastev Athanas
Published: June 2024

The influence of accelerated electrons on neuronal structures is scarcely explored compared to gamma and X-rays. This study aims to investigate the effects of accelerated electron radiation on some pivotal neurotransmitter circuits (cholinergic and serotonergic) of rats’ myenteric plexus. Male Wistar rats were irradiated with an electron beam (9 MeV, 5 Gy) generated by a multimodality linear accelerator. The contractile activity of isolated smooth muscle samples from the gastric corpus was measured. Furthermore, an electrical stimulation (200 μs, 20 Hz, 50 s, 60 V) was performed on the samples and an assessment of the cholinergic and serotonergic circuits was made. Five days after irradiation, the recorded mechanical responses were biphasic—contraction/relaxation in controls and contraction/contraction in irradiated samples. The nature of the contractile phase of control samples was cholinergic with serotonin involvement. The relaxation phase involved ACh-induced nitric oxide release from gastric neurons. There was a significant increase in serotonergic involvement during the first and second contractile phases of the irradiated samples, along with a diminished role of acetylcholine in the first phase. This study demonstrates an increased involvement of serotonergic neurotransmitter circuits in the gastric myenteric plexus caused by radiation with accelerated electrons.
Inhibition of Toll-like Receptors Alters Macrophage Cholesterol Efflux and Foam Cell Formation
Authors: Kim Jaemi , Kim Ji-Yun , Byeon Hye-Eun , Kim Ji-Won , Kim Hyoun-Ah , Suh Chang-Hee , Choi Sangdun , Linton MacRae F. , Jung Ju-Yang
Published: June 2024

Arterial macrophage cholesterol accumulation and impaired cholesterol efflux lead to foam cell formation and the development of atherosclerosis. Modified lipoproteins interact with toll-like receptors (TLR), causing an increased inflammatory response and altered cholesterol homeostasis. We aimed to determine the effects of TLR antagonists on cholesterol efflux and foam cell formation in human macrophages. Stimulated monocytes were treated with TLR antagonists (MIP2), and the cholesterol efflux transporter expression and foam cell formation were analyzed. The administration of MIP2 attenuated the foam cell formation induced by lipopolysaccharides (LPS) and oxidized low-density lipoproteins (ox-LDL) in stimulated THP-1 cells (p < 0.001). The expression of ATP-binding cassette transporters A (ABCA)-1, ABCG-1, scavenger receptor (SR)-B1, liver X receptor (LXR)-α, and peroxisome proliferator-activated receptor (PPAR)-γ mRNA and proteins were increased (p < 0.001) following MIP2 administration. A concentration-dependent decrease in the phosphorylation of p65, p38, and JNK was also observed following MIP2 administration. Moreover, an inhibition of p65 phosphorylation enhanced the expression of ABCA1, ABCG1, SR-B1, and LXR-α. TLR inhibition promoted the cholesterol efflux pathway by increasing the expression of ABCA-1, ABCG-1, and SR-B1, thereby reducing foam cell formation. Our results suggest a potential role of the p65/NF-kB/LXR-α/ABCA1 axis in TLR-mediated cholesterol homeostasis.
The Effect of Physical Activity/Exercise on miRNA Expression and Function in Non-Communicable Diseases—A Systematic Review
Authors: Afzal Moomna , Greco Francesca , Quinzi Federico , Scionti Francesca , Maurotti Samantha , Montalcini Tiziana , Mancini Annamaria , Buono Pasqualina , Emerenziani Gian Pietro
Published: June 2024

Exercise may differently affect the expression of key molecular markers, including skeletal muscle and circulating miRNAs, involved in cellular and metabolic pathways’ regulation in healthy individuals and in patients suffering from non-communicable diseases (NCDs). Epigenetic factors are emerging as potential therapeutic biomarkers in the prognosis and treatment of NCDs and important epigenetic factors, miRNAs, play a crucial role in cellular pathways. This systematic review aims to underline the potential link between changes in miRNA expression after different types of physical activity/exercise in some populations affected by NCDs. In June 2023, we systematically investigated the following databases: PubMed, MEDLINE, Scopus, and Web of Science, on the basis of our previously established research questions and following the PRISMA guidelines. The risk of bias and quality assessment were, respectively, covered by ROB2 and the Newcastle Ottawa scale. Of the 1047 records extracted from the initial search, only 29 studies were found to be eligible. In these studies, the authors discuss the association between exercise-modulated miRNAs and NCDs. The NCDs included in the review are cancer, cardiovascular diseases (CVDs), chronic obstructive pulmonary disease (COPD), and type 2 diabetes mellitus (T2DM). We evidenced that miR-146, miR-181, miR-133, miR-21, and miRNA-1 are the most reported miRNAs that are modulated by exercise. Their expression is associated with an improvement in health markers and they may be a potential target in terms of the development of future therapeutic tools.
Insights into the Clinical, Biological and Therapeutic Impact of Copy Number Alteration in Cancer
Authors: Carey-Smith Shannon L. , Kotecha Rishi S. , Cheung Laurence C. , Malinge Sébastien
Published: June 2024

Copy number alterations (CNAs), resulting from the gain or loss of genetic material from as little as 50 base pairs or as big as entire chromosome(s), have been associated with many congenital diseases, de novo syndromes and cancer. It is established that CNAs disturb the dosage of genomic regions including enhancers/promoters, long non-coding RNA and gene(s) among others, ultimately leading to an altered balance of key cellular functions. In cancer, CNAs have been associated with almost all steps of the disease: predisposition, initiation, development, maintenance, response to treatment, resistance, and relapse. Therefore, understanding how specific CNAs contribute to tumourigenesis may provide prognostic insight and ultimately lead to the development of new therapeutic approaches to improve patient outcomes. In this review, we provide a snapshot of what is currently known about CNAs and cancer, incorporating topics regarding their detection, clinical impact, origin, and nature, and discuss the integration of innovative genetic engineering strategies, to highlight the potential for targeting CNAs using novel, dosage-sensitive and less toxic therapies for CNA-driven cancer.
Integrative Analyses of Circulating Proteins and Metabolites Reveal Sex Differences in the Associations with Cardiac Function among DCM Patients
Authors: Hannemann Anke , Ameling Sabine , Lehnert Kristin , Dörr Marcus , Felix Stephan B. , Nauck Matthias , Al-Noubi Muna N. , Schmidt Frank , Haas Jan , Meder Benjamin , Völker Uwe , Friedrich Nele , Hammer Elke
Published: June 2024

Dilated cardiomyopathy (DCM) is characterized by reduced left ventricular ejection fraction (LVEF) and left or biventricular dilatation. We evaluated sex-specific associations of circulating proteins and metabolites with structural and functional heart parameters in DCM. Plasma samples (297 men, 71 women) were analyzed for proteins using Olink assays (targeted analysis) or LC-MS/MS (untargeted analysis), and for metabolites using LC MS/MS (Biocrates AbsoluteIDQ p180 Kit). Associations of proteins (n = 571) or metabolites (n = 163) with LVEF, measured left ventricular end diastolic diameter (LVEDDmeasured), and the dilation percentage of LVEDD from the norm (LVEDDacc. to HENRY) were examined in combined and sex-specific regression models. To disclose protein–metabolite relations, correlation analyses were performed. Associations between proteins, metabolites and LVEF were restricted to men, while associations with LVEDD were absent in both sexes. Significant metabolites were validated in a second independent DCM cohort (93 men). Integrative analyses demonstrated close relations between altered proteins and metabolites involved in lipid metabolism, inflammation, and endothelial dysfunction with declining LVEF, with kynurenine as the most prominent finding. In DCM, the loss of cardiac function was reflected by circulating proteins and metabolites with sex-specific differences. Our integrative approach demonstrated that concurrently assessing specific proteins and metabolites might help us to gain insights into the alterations associated with DCM.
Association between Circulating T Cells and the Gut Microbiome in Healthy Individuals: Findings from a Pilot Study
Authors: Vivek Sithara , Shen You Shan , Guan Weihua , Onyeaghala Guillaume , Oyenuga Mosunmoluwa , Staley Christopher , Karger Amy B. , Prizment Anna E. , Thyagarajan Bharat
Published: June 2024

Though the microbiome’s impact on immune system homeostasis is well documented, the effect of circulating T cells on the gut microbiome remains unexamined. We analyzed data from 50 healthy volunteers in a pilot trial of aspirin, using immunophenotyping and 16S rRNA sequencing to evaluate the effect of baseline T cells on microbiome changes over 6 weeks. We employed an unsupervised sparse canonical correlation analysis (sCCA) and used multivariable linear regression models to evaluate the association between selected T cell subsets and selected bacterial genera after adjusting for covariates. In the cross-sectional analysis, percentages of naïve CD4+ T cells were positively associated with a relative abundance of Intestinimonas, and the percentage of activated CD8+ T cells was inversely associated with Cellulosibacter. In the longitudinal analysis, the baseline percentages of naïve CD4+ T cells and activated CD4+ T cells were inversely associated with a 6-week change in the relative abundance of Clostridium_XlVb and Anaerovorax, respectively. The baseline percentage of terminal effector CD4+ T cells was positively associated with the change in Flavonifractor. Notably, the microbiome taxa associated with T cell subsets exclusively belonged to the Bacillota phylum. These findings can guide future experimental studies focusing on the role of T cells in impacting gut microbiome homeostasis.
Genetic Analysis of SCN11A, SCN10A, and SCN9A in Familial Episodic Pain Syndrome (FEPS) in Japan and Proposal of Clinical Diagnostic Criteria
Authors: Noguchi Atsuko , Tezuka Tohru , Okuda Hiroko , Kobayashi Hatasu , Harada Kouji H. , Yoshida Takeshi , Akioka Shinji , Wada Keiko , Takeya Aya , Kabata-Murasawa Risako , Kondo Daiki , Ishikawa Ken , Asano Takeshi , Fujiwara Michimasa , Hishikawa Nozomi , Mizukami Tomoyuki , Hitomi Toshiaki , Youssefian Shohab , Nagai Yoshihiro , Tanaka Manabu , Eto Kaoru , Shiraishi Hideaki , Amaya Fumimasa , Koizumi Akio , Takahashi Tsutomu
Published: June 2024

Familial episodic pain syndrome (FEPS) is an early childhood onset disorder of severe episodic limb pain caused mainly by pathogenic variants of SCN11A, SCN10A, and SCN9A, which encode three voltage-gated sodium channels (VGSCs) expressed as key determinants of nociceptor excitability in primary sensory neurons. There may still be many undiagnosed patients with FEPS. A better understanding of the associated pathogenesis, epidemiology, and clinical characteristics is needed to provide appropriate diagnosis and care. For this study, nationwide recruitment of Japanese patients was conducted using provisional clinical diagnostic criteria, followed by genetic testing for SCN11A, SCN10A, and SCN9A. In the cohort of 212 recruited patients, genetic testing revealed that 64 patients (30.2%) harbored pathogenic or likely pathogenic variants of these genes, consisting of 42 (19.8%), 14 (6.60%), and 8 (3.77%) patients with variants of SCN11A, SCN10A, and SCN9A, respectively. Meanwhile, the proportions of patients meeting the tentative clinical criteria were 89.1%, 52.0%, and 54.5% among patients with pathogenic or likely pathogenic variants of each of the three genes, suggesting the validity of these clinical criteria, especially for patients with SCN11A variants. These clinical diagnostic criteria of FEPS will accelerate the recruitment of patients with underlying pathogenic variants who are unexpectedly prevalent in Japan.
Assessment of the Impact of Trace Essential Metals on Cancer Development
Authors: Górska Aleksandra , Markiewicz-Gospodarek Agnieszka , Trubalski Mateusz , Żerebiec Marta , Poleszak Julia , Markiewicz Renata
Published: June 2024

This study examines the impact of zinc, copper, cobalt, iron, and manganese on cancer development, considering their dual roles as potential promoters or inhibitors within tumorigenesis. A comprehensive analysis of existing literature and experimental data is conducted to elucidate the intricate relationship between these trace elements and cancer progression. The findings highlight the multifaceted effects of zinc, copper, cobalt, iron, and manganese on various aspects of cancer development, including cell proliferation, angiogenesis, and metastasis. Understanding the nuanced interactions between these trace elements and cancer could offer crucial insights into tumorigenesis mechanisms and facilitate the identification of novel biomarkers and therapeutic targets for cancer prevention and treatment strategies. This research underscores the importance of considering the roles of essential trace elements in cancer biology and may ultimately contribute to advancements in precision medicine approaches for combating cancer.
Integrating In Silico and In Vitro Approaches to Identify Natural Peptides with Selective Cytotoxicity against Cancer Cells
Authors: Kao Hui-Ju , Weng Tzu-Han , Chen Chia-Hung , Chen Yu-Chi , Chi Yu-Hsiang , Huang Kai-Yao , Weng Shun-Long
Published: June 2024

Anticancer peptides (ACPs) are bioactive compounds known for their selective cytotoxicity against tumor cells via various mechanisms. Recent studies have demonstrated that in silico machine learning methods are effective in predicting peptides with anticancer activity. In this study, we collected and analyzed over a thousand experimentally verified ACPs, specifically targeting peptides derived from natural sources. We developed a precise prediction model based on their sequence and structural features, and the model’s evaluation results suggest its strong predictive ability for anticancer activity. To enhance reliability, we integrated the results of this model with those from other available methods. In total, we identified 176 potential ACPs, some of which were synthesized and further evaluated using the MTT colorimetric assay. All of these putative ACPs exhibited significant anticancer effects and selective cytotoxicity against specific tumor cells. In summary, we present a strategy for identifying and characterizing natural peptides with selective cytotoxicity against cancer cells, which could serve as novel therapeutic agents. Our prediction model can effectively screen new molecules for potential anticancer activity, and the results from in vitro experiments provide compelling evidence of the candidates’ anticancer effects and selective cytotoxicity.
The Induction of Salt Stress Tolerance by Gibberellic Acid Treatment in Stevia rebaudiana Bertoni Plants
Authors: Janah Iman , Ben-Laouane Raja , Elhasnaoui Abdelhadi , Anli Mohamed , Meddich Abdelilah
Published: June 2024

Salinity poses a perpetual threat to agricultural lands, presenting an ongoing challenge to global food security. The present study aimed to explore the potential benefits of gibberellic acid (GA3) in enhancing stevia’s tolerance to salt stress. The experimental treatments comprised a control group (C) with 0 mM NaCl, salt stress (S) with 80 mM NaCl, 50 ppm of GA3 (G1), 100 ppm of GA3 (G2), as well as combinations of GA3 with salt stress (G1+S and G2+S). Exposure to saline water (80 mM NaCl) significantly decreased plant growth, water status, and photosynthetic attributes. However, it also led to notable increases in proline, glycine betaine, malondialdehyde (MDA), and antioxidant enzyme activities compared to the control treatment. Application of 100 ppm of GA3 effectively alleviated salt stress by enhancing plant performance under saline conditions, as evidenced by increased aerial (54%) and root (31%) dry weights compared to the control. Additionally, GA3 treatment resulted in elevated activities of polyphenol oxidase (24%), peroxidase (12%), superoxide dismutase (31%), and catalase (11%) while reducing MDA content by 41%, electrolyte leakage by 37%, and hydrogen peroxide by 34%. The use of phytohormones such as GA3 emerges as a promising strategy for mitigating salt stress-induced damage. It not only enhances plant performance but also reduces oxidative stress, offering protection against the detrimental effects of soil salinization.
Strategic Management of Workforce Diversity: An Evolutionary Game Theory Approach as a Foundation for AI-Driven Systems
Authors: Talajić Mirko , Vrankić Ilko , Pejić Bach Mirjana
Published: June 2024

In the complex organisational landscape, managing workforce diversity effectively has become crucial due to rapid technological advancements and shifting societal values. This study explores strategic workforce management through the novel methodological framework consisting of the evolutionary game theory concept integrated with replicator dynamics and traditional game theory, addressing a notable gap in the literature and suggesting an evolutionarily stable workforce structure. Key findings indicate that targeted rewards for the most Enthusiastic employee type can reduce overall costs and enhance workforce efficiency, although managing a diverse team remains complex. The study reveals that while short-term incentives boost immediate productivity, long-term rewards facilitate favourable behavioural changes, which are crucial for sustaining organisational performance. Additionally, the role of artificial intelligence (AI) is highlighted, emphasising its potential to integrate with these theoretical models, thereby enhancing decision-making processes. The study underscores the importance of strategic leadership in navigating these dynamics, suggesting that leaders must tailor their approaches to balance short-term incentives and long-term rewards to maintain an optimal workforce structure.
Life Table Study of Liriomyza trifolii and Its Contribution to Thermotolerance: Responding to Long-Term Selection Pressure for Abamectin Resistance
Authors: Wang Yucheng , Chang Yawen , Gong Weirong , Du Yuzhou
Published: June 2024

Liriomyza trifolii is a significant invasive pest that targets horticultural and vegetable crops, causing large-scale outbreaks characterized by pronounced thermotolerance and insecticide resistance. This study examined the impact of long-term selection for abamectin resistance during the larval stage of L. trifolii on its population dynamics and thermal tolerance. We conducted a comprehensive comparison between the abamectin-resistant strain (AB-R) and the susceptible strain (S), including age-stage, two-sex life table analysis, thermal preference (Tpref), critical thermal maximum (CTmax), heat knockdown times (HKDTs), eclosion and survival rates, and LtHsp expression under heat stress. Our results showed that while selection for abamectin resistance was detrimental to survival and reproduction, it activated self-defense mechanisms and rapid adaptive adjustments and conferred modest thermal tolerance, which suggests a dual nature of insecticide effects. The AB-R strain exhibited significantly higher thermal preference and CTmax values, along with a longer HKDT and improved survival. Additionally, there was a significant upregulation of LtHsp expression in the AB-R strain compared to the S strain. These findings indicate that the evolution of thermal adaptation was accompanied by abamectin resistance development, emphasizing the necessity of considering temperature effects when applying chemical control. Our study provides valuable insights into how physiological acclimation may help mitigate the toxic effects of insecticides and illustrate how insects respond to multiple environmental pressures.
A Mysterious Asian Firefly Genus, Oculogryphus Jeng, Engel & Yang (Coleoptera, Lampyridae): The First Complete Mitochondrial Genome and Its Phylogenetic Implications
Authors: Yang Yu-Xia , Kang Ya , Ge Xue-Ying , Yuan Shuai-Long , Li Xue-Yan , Liu Hao-Yu
Published: June 2024

The firefly genus Oculogryphus Jeng, Engel & Yang, 2007 is a rare-species group endemic to Asia. Since its establishment, its position has been controversial but never rigorously tested. To address this perplexing issue, we are the first to present the complete mitochondrial sequence of Oculogryphus, using the material of O. chenghoiyanae Yiu & Jeng, 2018 determined through a comprehensive morphological identification. Our analyses demonstrate that its mitogenome exhibits similar characteristics to that of Stenocladius, including a rearranged gene order between trnC and trnW, and a long intergenic spacer (702 bp) between the two rearranged genes, within which six remnants (29 bp) of trnW were identified. Further, we incorporated this sequence into phylogenetic analyses of Lampyridae based on different molecular markers and datasets using ML and BI analyses. The results consistently place Oculogryphus within the same clade as Stenocladius in all topologies, and the gene rearrangement is a synapomorphy for this clade. It suggests that Oculogryphus should be classified together with Stenocladius in the subfamily Ototretinae at the moment. This study provides molecular evidence confirming the close relationship between Oculogryphus and Stenocladius and discovers a new phylogenetic marker helpful in clarifying the monophyly of Ototretinae, which also sheds a new light on firefly evolution.
Surgical Management of Ischemic Cardiomyopathy Patients with Severe Left Ventricular Dysfunction: Is It Time to Reconsider Revascularization Surgery?
Authors: Masroor Matiullah , Wang Yixuan , Zhang Chao , Dong Nianguo
Published: June 2024

Ischemic cardiomyopathy patients with severe left ventricular dysfunction are a specific group of patients with poor surgical outcomes. There are few surgical treatment options in practice for the treatment of these patients such as heart transplantation, coronary artery bypass surgery, surgical ventricular restoration, etc. Despite multiple treatment options, there are no explicit clinical guidelines available to guide surgeons in choosing the most appropriate option and ensuring that the specific patient can benefit from the selected surgical treatment. Heart transplantation is the gold standard treatment for ischemic cardiomyopathy patients with severe left ventricular dysfunction, but it is limited to very few highly equipped centers around the world due to donor shortages, complex perioperative and surgical management, and limited technological and human resources. It is evident from some studies that heart transplant-eligible candidates can benefit from alternative surgical options such as coronary artery bypass surgery alone or combined with surgical ventricular restoration. Therefore, alternative surgical options that are used for most of the population, especially in developing and underdeveloped countries, need to be discussed to improve their outcomes. A challenge in the recent era which has yet to find a solution is to determine which heart transplant candidate can benefit from simple revascularization compared to a complex heart transplantation procedure. Myocardial viability testing was one of the most important determinants in deciding whether a patient should undergo revascularization, but its role in guiding appropriate surgical options has been challenged. This review aims to discuss the available surgical management options and their long-term outcomes for patients with ischemic cardiomyopathy, which will eventually help surgeons when choosing a surgical procedure.
A Vector Theory of Assessing Clinical Trials: An Application to Bioequivalence
Authors: Karalis Vangelis D.
Published: June 2024

A novel idea is introduced regarding the statistical comparisons of endpoints in clinical trials. Currently, the (dis)similarity of measured endpoints is not assessed. Instead, statistical analysis is directly applied, which can lead to multiplicity issues, reduced statistical power, and the recruitment of more subjects. The Vector-Based Comparison (VBC) approach originates from vector algebra and considers clinical endpoints as “vectors”. In the general case of N clinical endpoints, a Cartesian coordinate system is defined, and the most important primary endpoint (E1) is set. Following an explicitly defined procedure, the pairwise relationships of the remaining N-1 endpoints with E1 are estimated, and the N-1 endpoints are decomposed into axes perpendicular to E1. The angle between vectors provides insight into the level of dependency between variables. Vectors that are perpendicular to each other are considered independent, and only these are used in the statistical analysis. In this work, VBC is applied to bioequivalence studies of three anti-hypertensive drugs: amlodipine, irbesartan, and hydrochlorothiazide. The results suggest that VBC is a reproducible, easily applicable method allowing for the discrimination and utilization of the endpoint component expressing different attributes. All clinical characteristics are assessed with increased statistical power, without inflation of type I error.
Changes in Cardiac Structure and Function of Recipients after Kidney Transplantation
Authors: Akkaya Suleyman , Cakmak Umit
Published: June 2024

Background: Chronic kidney disease (CKD) elevates the risk of cardiovascular disease (CVD) and mortality. Uremic cardiomyopathy, frequently observed in CKD and end-stage renal disease (ESRD), involves alterations in cardiac structure and function, which may reverse post-kidney transplantation, although data remain controversial. This study examines the relationship between graft function and changes in cardiac parameters pre- and post-transplantation in kidney transplant recipients. Methods: A total of 145 pediatric and adult recipients of living or deceased donor kidney transplants were enrolled at Gazi Yaşargil Training and Research Hospital. This cohort study utilized transthoracic echocardiographic (TTE) imaging pre-transplant and at least two years post-transplant. Echocardiographic parameters were analyzed using standard techniques. Results: The mean age of the participants was 35 years, with 60% male. The average dialysis duration prior to transplantation was 27 months. Most recipients (83.4%) received kidneys from living donors. Left ventricular diastolic dysfunction increased significantly post-transplant (p < 0.05), while other cardiac dimensions and functions, such as ejection fraction and pulmonary artery pressure, showed no significant change (p > 0.05). Notably, diastolic dysfunction worsened in patients with dysfunctional grafts (GFR < 45), correlating with increased pulmonary artery pressure post-transplant. The rate of antihypertensive drug use and the prevalence of diabetes mellitus increased significantly post-transplant (p < 0.05). Conclusions: This study demonstrates that left ventricular diastolic dysfunction present before kidney transplantation continues to persist post-transplantation in patients with end-stage renal disease undergoing chronic kidney disease treatment. Furthermore, it shows an increased rate of pulmonary artery pressure and pericardial effusion in patients with dysfunctional grafts after transplantation. Further research is required to explore strategies to reverse uremic cardiomyopathy and reduce cardiovascular risk in these patients.
Comparison of the Effects of Postoperative Arm Restraints and Mittens on Cleft Lip Scar Quality after Primary Repair
Authors: Verzella Alexandra N. , Laspro Matteo , Diaz Allison , Cassidy Michael F. , Park Jenn , Schechter Jill , Alcon Andre , Shetye Pradip R. , Staffenberg David A. , Flores Roberto L.
Published: June 2024

Introduction: Postoperative management following primary cleft lip repair varies across institutions, cleft care teams, and individual surgeons. Postoperative precautions employed after cleft lip repair include dietary restrictions, pacifier limitations, and immobilization, with arm restraints long being used. Yet, restraint distress has led to the exploration of other forms of immobilization. Thus, this study aims to assess cleft lip scar quality and complication rates after postoperative immobilization with arm restraints versus hand mittens. Methods: A retrospective review of patients with unilateral cleft who underwent primary repair with the senior surgeon was done. Data on demographics, surgical characteristics, and immobilization utilized were gathered. A survey with pictures of postoperative scars were sent to laypeople who assessed scar quality with Modified Scar-Rating Scale scores for surface appearance, height, and color of the scar tissue. Statistical analysis was carried out for significance. Results: Twenty-eight patients with a unilateral cleft underwent arm restraints after primary lip repair, and twenty-seven utilized mittens. In total, 42 medical students completed the scar assessment. Photographs were taken an average of 23.9 (±5.8) and 28.2 (±11.9) months postoperatively in the restraint and mitten groups, respectively (p = 0.239). There were no statistically significant differences in scores between scar surface, height, color, or overall scar appearance. Complication rates were also similar between groups. Conclusions: Arm restraints appear to have no additional benefit relative to scar quality, as compared to mittens. Considering the arm restraints’ burden of care, mittens should be considered as a measure to protect the lip after primary repair.
Antithrombotic Therapy in Patients Undergoing Transcatheter Aortic Valve Implantation
Authors: Pallante Francesco , Costa Francesco , Garcia Ruiz Victoria , Vizzari Giampiero , Iannello Pietro , Teresi Lucio , Carciotto Gabriele , Lo Giudice Stefania , Iuvara Giustina , Laterra Giulia , Regueiro Ander , Giustino Gennaro , Alonso Briales Juan Horacio , Hernandez Jose Maria , Barbanti Marco , Micari Antonio , Patanè Francesco
Published: June 2024

Transcatheter aortic valve implantation (TAVI) now represents the mainstay of treatment for severe aortic stenosis. Owing to its exceptional procedural efficacy and safety, TAVI has been extended to include patients at lower surgical risk, thus now encompassing a diverse patient population receiving this treatment. Yet, long-term outcomes also depend on optimal medical therapy for secondary vascular prevention, with antithrombotic therapy serving as the cornerstone. Leveraging data from multiple randomized controlled trials, the current guidelines generally recommend single antithrombotic therapy, with either single antiplatelet therapy (SAPT) or oral anticoagulation (OAC) alone in those patients without or with atrial fibrillation, respectively. Yet, individualization of this pattern, as well as specific case uses, may be needed based on individual patient characteristics and concurrent procedures. This review aims to discuss the evidence supporting antithrombotic treatments in patients treated with TAVI, indications for a standardized treatment, as well as specific considerations for an individualized approach to treatment.
A Radiation-Free Approach Based on the Whole-Body MRI Has Shown a High Level of Accuracy in the Follow-Up of Lymphoma Patients—A Single Center Retrospective Study
Authors: Frolli Antonio , Varvello Sivlia , Balbo Mussetto Annalisa , Gottardi Daniela , Bullo Martina , Marini Silvia , Saglio Giuseppe , Cirillo Stefano , Cilloni Daniela , Parvis Guido Eugenio
Published: June 2024

Background: Recurrence, even after years from the last treatment, characterizes lymphoproliferative disorders. Therefore, patients in complete remission from the disease should be followed up with periodic clinical checks. There is not a consensus on the role of imaging for this aim, because the radiological techniques used at the time of diagnosis expose patients to a risk of ionizing radiation damage. Whole-body magnetic resonance imaging with diffusion-weighted imaging (WB-MRI-DWI) has given similar results to gold standard techniques in detecting lymphoma in the involved sites without ionizing radiation. In this retrospective real-life study, we aimed to assess the accuracy of WB-MRI-DWI during follow-ups of lymphoma patients in terms of sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). Methods: Lymphoma patients who were subject to at least one WB-MRI-DWI during follow-up between February 2010 and February 2022 were enrolled. Results: Based on our investigation, the calculated sensitivity of WB-MRI-DWI was 100% (95% CI: 99.4–100.0), the specificity was 98.6% (95% CI: 97.4–99.3), PPV was 79% (95% CI: 75.9–81.9), and NPV was 100% (95% CI: 99.4–100.0). Conclusions: Despite the possibility of poor patient compliance and the identification of false positives, WB-MRI-DWI examination demonstrated an excellent sensitivity in ruling out the disease relapse.
Efficacy and Safety of Chemotherapy after Immunotherapy in Patients with Advanced Non-Small-Cell Lung Cancer
Authors: Camerini Andrea , Mazzoni Francesca , Scotti Vieri , Tibaldi Carmelo , Sbrana Andrea , Calabrò Luana , Caliman Enrico , Ciccone Lucia Pia , Bernardini Laura , Graziani Jessica , Grosso Maria Antonietta , Chella Antonio , Allegrini Giacomo , Amoroso Domenico , Baldini Editta
Published: June 2024

Background: There are currently few data about the safety and effectiveness of chemotherapy for patients with metastatic non-small-cell lung cancer (NSCLC) who have progressed from prior immunotherapy. Methods: Data from patients with consecutive stage IIIB–IV, ECOG performance status (PS) 0–2, non-small-cell lung cancer (NSCLC) treated with combination or single-agent chemotherapy following progression on an earlier immunotherapy regimen were retrospectively gathered. Recorded were baseline attributes, outcome metrics, and toxicities. The neutrophil/lymphocyte (N/L) ratio’s predictive usefulness was examined through an exploratory analysis. Results: The analysis comprised one hundred subjects. The adeno/squamous carcinoma ratio was 77%/23%, the M/F ratio was 66%/34%, the ECOG PS was 0/1/≥2 47%/51%/2%, and the median PD-L1 expression was 50% (range 0–100). The median age was 67 (range 39–81) years. Prior immunotherapy included a single-agent treatment in 83% of cases, with pembrolizumab use being prevalent, and a median N/L ratio of four prior to chemotherapy. The overall median time-to-progression on previous immunotherapy was 6 months. After immunotherapy, just 33% of subjects underwent chemotherapy. A median of 4 (range 1–16) cycles of chemotherapy were administered; platinum doublets (primarily carboplatin) were delivered in only 31% of cases, vinorelbine accounted for 25%, taxanes for 25%, and gemcitabine for 8%. The median clinical benefit was 55%, while the overall response rate was 21%. The median overall survival was 5 months (range 1–22) and the median time to progression was 4 months (range 1–17). Subgroups with low and high N/L ratios were compared, but there was no discernible difference in survival. Conclusions: After immunotherapy, a small percentage of patients with advanced NSCLC had chemotherapy. Following immunotherapy advancement, chemotherapy demonstrated a moderate level of therapeutic effectiveness; no adverse concerns were noted. The effectiveness of chemotherapy following immunotherapy was not predicted by the baseline N/L ratio.
Surgical Outcomes of Different Deep Anterior Lamellar Keratoplasty Techniques—A Single-Centre UK Study
Authors: Elalfy Mohamed , Negm Ahmed , Soliman Shady , Naveed Hasan , Hamada Samer , Matsou Artemis , Hassan Mansour , Atef Ahmed , Gatzioufas Zisis , Mahran Waleed
Published: June 2024

Background: Anterior lamellar keratoplasty (ALK) is a less invasive procedure than PK, and thus avoids many of the intraocular complications associated with PK. DALK can be performed using several different techniques, with either a manual dissection, a keratome or femtosecond-laser assisted dissection, or with a big bubble technique. To analyse the outcomes and compare the results of three deep anterior lamellar keratoplasty (DALK) techniques. Methods: This study included 105 DALK cases performed at Queen Victoria Hospital, East Grinstead, UK, in the period between January 2016 and May 2022. Cases were classified into four groups based on technique: BB-DALK, manual DALK, FS-DALK and ‘converted to PK group’. Results: There was significant improvement in VA and Kmax compared to the preoperative values in all groups. There was no significant difference detected in VA and Kmax between all groups. Conclusions: Performing DALK surgery with any suitable technique (manual, big-bubble or femtosecond-assisted) is effective and causes significant improvements in VA and Kmax, even in cases where a conversion to penetrating keratoplasty is required. However, every technique has its pros and cons and should be tailored according to surgeon preference and individual case pathology.
Upper-Limb Muscle Fatigability in Para-Athletes Quantified as the Rate of Force Development in Rapid Contractions of Submaximal Amplitude
Authors: Boccia Gennaro , Brustio Paolo Riccardo , Beratto Luca , Peluso Ilaria , Ferrara Roberto , Munzi Diego , Toti Elisabetta , Raguzzini Anna , Sciarra Tommaso , Rainoldi Alberto
Published: June 2024

This study aimed to compare neuromuscular fatigability of the elbow flexors and extensors between athletes with amputation (AMP) and athletes with spinal cord injury (SCI) for maximum voluntary force (MVF) and rate of force development (RFD). We recruited 20 para-athletes among those participating at two training camps (2022) for Italian Paralympic veterans. Ten athletes with SCI (two with tetraplegia and eight with paraplegia) were compared to 10 athletes with amputation (above the knee, N = 3; below the knee, N = 6; forearm, N = 1). We quantified MVF, RFD at 50, 100, and 150 ms, and maximal RFD (RFDpeak) of elbow flexors and extensors before and after an incremental arm cranking to voluntary fatigue. We also measured the RFD scaling factor (RFD-SF), which is the linear relationship between peak force and peak RFD quantified in a series of ballistic contractions of submaximal amplitude. SCI showed lower levels of MVF and RFD in both muscle groups (all p values ≤ 0.045). Despite this, the decrease in MVF (Cohen’s d = 0.425, p < 0.001) and RFDpeak (d = 0.424, p = 0.003) after the incremental test did not show any difference between pathological conditions. Overall, RFD at 50 ms showed the greatest decrease (d = 0.741, p < 0.001), RFD at 100 ms showed a small decrease (d = 0.382, p = 0.020), and RFD at 150 ms did not decrease (p = 0.272). The RFD-SF decreased more in SCI than AMP (p < 0.0001). Muscle fatigability impacted not only maximal force expressions but also the quickness of ballistic contractions of submaximal amplitude, particularly in SCI. This may affect various sports and daily living activities of wheelchair users. Early RFD (i.e., ≤50 ms) was notably affected by muscle fatigability.
Color Biomimetics in Textile Design: Reproduction of Natural Plant Colors through Instrumental Colorant Formulation
Authors: Cabral Isabel , Schuch Amanda , Steffens Fernanda
Published: June 2024

This paper explores the intersection of colorimetry and biomimetics in textile design, focusing on mimicking natural plant colors in dyed textiles via instrumental colorant formulation. The experimental work was conducted with two polyester substrates dyed with disperse dyes using the exhaustion process. Textiles dyed with different dye colors and concentrations were measured in a spectrophotometer and a database was created in Datacolor Match Textile software version 2.4.1 (0) with the samples’ colorimetric properties. Colorant recipe formulation encompassed the definition and measurement of the pattern colors (along four defined natural plants), the selection of the colorants, and the software calculation of the recipes. After textile dyeing with the lowest expected CIELAB color difference (ΔE*) value recipe for each pattern color, a comparative analysis was conducted by spectral reflectance and visual assessment. Scanning electron microscopy and white light interferometry were also used to characterize the surface of the natural elements. Samples dyed with the formulated recipe attained good chromatic similarity with the respective natural plants’ colors, and the majority of the samples presented ΔE* between 1.5 and 4.0. Additionally, recipe optimization can also be conducted based on the colorimetric evaluation. This research contributes a design framework for biomimicking colors in textile design, establishing a systematic method based on colorimetry and color theory that enables the reproduction of nature’s color palette through the effective use of colorants.
Effect of Licorice on Gene Expression Related to the Growth of Asian Seabass Lates calcarifer
Authors: Yang Rui , Zhao Wang , Wang Yifu , Fu Zhengyi , Hu Jing , Zhou Shengjie , Li Minghao , Ma Zhenhua
Published: June 2024

The Asian seabass (Lates calcarifer) has high economic value and is the primary aquaculture species in China. Licorice (Glycyrrhiza uralensis) as a feed additive has demonstrated significant immunological benefits in aquaculture. However, its effects on the growth of aquatic animals are largely unexplored. This study explored the influence of licorice on the level of growth-related genes in Asian seabass by conducting an experiment using artificial feed with 0%, 1%, 3%, and 5% licorice. The impact on growth performance and the expression of several genes, including growth hormone–releasing hormone (GHRH), growth hormone (GH), growth hormone receptor (GHR), insulin-like growth factor 1 (IGF1), IGF2, IGF2 receptor (IGF2R), myostatin 1 (MSTN1), and myostatin 2 (MSTN2), were studied over 56 d. According to the results, the 3% and 5% licorice-supplemented diets significantly improved survival rates and weight gain compared to the control group. Licorice affected the level of growth-associated genes in Asian seabass and significantly increased the levels of GHR and IGF1 in the liver. However, a 5% licorice diet downregulated the expression of IGF2. As the licorice content in the diet increased, the levels of IGF2R and MSTN1 in the muscle tissue first decreased and then increased, and licorice addition inhibited the MSTN2 expression. The inclusion of licorice in the feed led to a significant downregulation of the GH and GHRH expression (p < 0.05). In summary, adding a certain proportion of licorice to the diet can improve the survival rate of the Asian seabass. Moreover, a proper proportion of licorice can increase the expression of related growth genes of fish, effectively increasing their weight gain rate and specific growth rate.