bluuebunny/crossref_metadata_2025 huggingface dataset:
Dynamic Deconstructive Psychotherapy for Suicidal Adolescents: Effectiveness of Routine Care in an Outpatient Clinic
Authors: Shields Rebecca J. , Helfrich Jessica P. , Gregory Robert J.
Published: July 2024

Suicidal behavior and demand for services have been increasing in adolescents. Many of the current treatments are focused on symptom mitigation, crisis management, and safety planning; however, few are aimed at remediating underlying vulnerabilities that may be contributing to suicide risk. Dynamic Deconstructive Psychotherapy (DDP) has been found to be effective for suicidal adults but has never been studied for adolescents. The present study examined real-world outcomes of 65 suicidal adolescents, aged 13–17 years, receiving weekly DDP in an outpatient clinic. The primary outcome was change in suicide ideation from baseline to 6 months of treatment as assessed by the Suicide Ideation Subscale of the Columbia Suicide Severity Rating Scale. In intent-to-treat analyses, suicide ideation significantly decreased over the 6 months with a large treatment effect (d = 1.19). Secondary measures, such as suicide attempts, self-harm, depression, anxiety, disability, self-compassion, and inpatient utilization, also improved significantly. Among the 42 adolescents (65%) who completed at least 6 months of treatment, suicide attempts decreased by 84%. DDP may be effective in reducing suicide ideation and other risk factors in suicidal adolescents and may be cost-effective given reduced inpatient utilization. These initial promising findings warrant further research and development.
Parental Mental Health, Gender, and Lifestyle Effects on Post-Pandemic Child and Adolescent Psychosocial Problems: A Cross-Sectional Survey in Northern Italy
Authors: Barbieri Verena , Piccoliori Giuliano , Engl Adolf , Wiedermann Christian J.
Published: July 2024

Background: The exacerbation of psychosocial problems among children and adolescents during the coronavirus disease 2019 (COVID-19) pandemic necessitates an assessment of the long-term mental health impact of pandemic interventions. Focusing on both pandemic-related factors and demographic variables, such as gender and daily habits, an analysis was conducted to understand how these elements continue to affect young populations in the post-pandemic era. Methods: In April 2023, a comprehensive online survey was administered to families in South Tyrol, Italy, with children aged 7–19 years, to ensure age and gender representation. The survey included parent ratings and adolescent (11–19 years) self-reports using standardized instruments to measure the symptoms of mental health problems (Strengths and Difficulties Questionnaire, SDQ), anxiety (Screen for Child Anxiety Related Emotional Disorders, SCARED), and depression (Patient Health Questionnaire-2, PHQ-2). Statistical analyses included descriptive statistics, chi-square tests, and unadjusted odds ratios (ORs). Results: Of the 4525 valid responses, 1831 were self-reported by adolescents. Notable gender differences in mental health outcomes were identified, along with significant demographic predictors, such as age, single parenthood, parental mental health problems, and immigrant background. Negative effects were associated with reduced family climate and increased screen time, whereas physical activity showed beneficial effects. Proxy reports overestimated adolescents’ mental health problems, whereas self-reports tended to underestimate them. Conclusions: Persistent mental health problems and gender disparities highlight the need for a public health approach. This should include accessible support services, resilience building, targeted support for vulnerable families and gender-specific interventions.
Aerobic Exercise in the Aquatic Environment Suppresses the Plasma Renin Activity in Individuals with Type 2 Diabetes: A Secondary Analysis of a Randomized Clinical Trial
Authors: Delevatti Rodrigo Sudatti , Leonel Larissa dos Santos , Rodrigues João Gabriel da Silveira , Kanitz Ana Carolina , Alberton Cristine Lima , Lovatel Gisele Agustini , Siqueira Ionara Rodrigues , Kruel Luiz Fernando Martins
Published: July 2024

To compare the acute effects of aquatic walking/running versus dry-land walking/running on blood glucose and plasma renin activity (PRA) in individuals with type 2 diabetes, participants with type 2 diabetes performed deep-water or dry-land walking and/or running sessions in a swimming pool or on an athletics track, respectively. Both sessions comprised seven blocks of 3 min at 85–90% of the heart rate deflection point (HRDP), interspersed with 2 min at <85% HRDP, totaling 35 min, with a 48 h interval between sessions. PRA and blood glucose were assessed before and immediately after the sessions. Generalized estimation equations were used to verify the session effects, with the Bonferroni post hoc test, considering the significance level as 0.05. Twelve individuals (53.2 ± 8.9 years) diagnosed with type 2 diabetes for 6.3 ± 6.34 years participated in the study. A reduction in PRA was found only after the aquatic session (−7.75 ng/mL/h; −69%; p: 0.034), while both aquatic and dry-land sessions similarly reduced the blood glucose levels (aquatic: −38 mg/dL, −21%; dry-land: −26 mg/dL, −14%; time effect, p = 0.007). Despite yielding similar glycemic reductions as dry-land walking/running, aquatic walking/running led to an expressive decrease in PRA among individuals with type 2 diabetes.
Factors Associated with Legionella Detection in the Water Systems of National Lodging Organization Facilities with Water Management Programs in the United States
Authors: Kahn Rebecca , Derado Gordana , Hannapel Elizabeth J. , Vander Kelen Patrick , Kunz Jasen M. , Edens Chris
Published: July 2024

A better understanding of risk factors and the predictive capability of water management program (WMP) data in detecting Legionella are needed to inform the efforts aimed at reducing Legionella growth and preventing outbreaks of Legionnaires’ disease. Using WMPs and Legionella testing data from a national lodging organization in the United States, we aimed to (1) identify factors associated with Legionella detection and (2) assess the ability of WMP disinfectant and temperature metrics to predict Legionella detection. We conducted a logistic regression analysis to identify WMP metrics associated with Legionella serogroup 1 (SG1) detection. We also estimated the predictive values for each of the WMP metrics and SG1 detection. Of 5435 testing observations from 2018 to 2020, 411 (7.6%) had SG1 detection, and 1606 (29.5%) had either SG1 or non-SG1 detection. We found failures in commonly collected WMP metrics, particularly at the primary test point for total disinfectant levels in hot water, to be associated with SG1 detection. These findings highlight that establishing and regularly monitoring water quality parameters for WMPs may be important for preventing Legionella growth and subsequent disease. However, while unsuitable water quality parameter results are associated with Legionella detection, this study found that they had poor predictive value, due in part to the low prevalence of SG1 detection in this dataset. These findings suggest that Legionella testing provides critical information to validate if a WMP is working, which cannot be obtained through water quality parameter measurements alone.
The Epigenetic Modifiers HDAC2 and HDAC7 Inversely Associate with Cancer Stemness and Immunity in Solid Tumors
Authors: Maciejewski Kacper , Giers Marek , Oleksiewicz Urszula , Czerwinska Patrycja
Published: July 2024

Dysregulation of histone deacetylases (HDACs) is closely associated with cancer development and progression. Here, we comprehensively analyzed the association between all HDAC family members and several clinicopathological and molecular traits of solid tumors across 22 distinct tumor types, focusing primarily on cancer stemness and immunity. To this end, we used publicly available TCGA data and several bioinformatic tools (i.e., GEPIA2, TISIDB, GSCA, Enrichr, GSEA). Our analyses revealed that class I and class II HDAC proteins are associated with distinct cancer phenotypes. The transcriptomic profiling indicated that class I HDAC members, including HDAC2, are positively associated with cancer stemness, while class IIA HDAC proteins, represented by HDAC7, show a negative correlation to cancer stem cell-like phenotypes in solid tumors. In contrast to tumors with high amounts of HDAC7 proteins, the transcriptome signatures of HDAC2-overexpressing cancers are significantly enriched with biological terms previously determined as stemness-associated genes. Moreover, high HDAC2-expressing tumors are depleted with immune-related processes, and HDAC2 expression correlates with tumor immunosuppressive microenvironments. On the contrary, HDAC7 upregulation is significantly associated with enhanced immune responses, followed by enriched infiltration of CD4+ and CD8+ T cells. This is the first comprehensive report demonstrating robust and versatile associations between specific HDAC family members, cancer dedifferentiation, and anti-tumor immune statuses in solid tumors.
The Influence of BMP6 on Serotonin and Glucose Metabolism
Authors: Milešević Marina , Matić Jelić Ivona , Rumenović Viktorija , Ivanjko Natalia , Vukičević Slobodan , Bordukalo-Nikšić Tatjana
Published: July 2024

Previous studies have suggested a potential role of bone morphogenetic protein 6 (BMP6) in glucose metabolism, which also seems to be regulated by serotonin (5-hydroxytryptamine, 5HT), a biogenic amine with multiple roles in the organism. In this study, we explored possible interactions between BMP6, serotonin, and glucose metabolism regulation. The effect of BMP6 or 5HT on pancreatic β-cells has been studied in vitro using the INS-1 832/13 rat insulinoma cell line. Studies in vivo have been performed on mice with the global deletion of the Bmp6 gene (BMP6−/−) and included glucose and insulin tolerance tests, gene expression studies using RT-PCR, immunohistochemistry, and ELISA analyses. We have shown that BMP6 and 5HT treatments have the opposite effect on insulin secretion from INS-1 cells. The effect of BMP6 on the 5HT system in vivo depends on the tissue studied, with no observable systemic effect on peripheral 5HT metabolism. BMP6 deficiency does not cause diabetic changes, although a mild difference in insulin tolerance test between BMP6−/− and WT mice was observed. In conclusion, BMP6 does not directly influence glucose metabolism, but there is a possibility that its deletion causes slowly developing changes in glucose and serotonin metabolism, which would become more expressed with ageing.
Free Fatty Acids and Free Fatty Acid Receptors: Role in Regulating Arterial Function
Authors: Yu Fengzhi , Zong Boyi , Ji Lili , Sun Peng , Jia Dandan , Wang Ru
Published: July 2024

The metabolic network’s primary sources of free fatty acids (FFAs) are long- and medium-chain fatty acids of triglyceride origin and short-chain fatty acids produced by intestinal microorganisms through dietary fibre fermentation. Recent studies have demonstrated that FFAs not only serve as an energy source for the body’s metabolism but also participate in regulating arterial function. Excess FFAs have been shown to lead to endothelial dysfunction, vascular hypertrophy, and vessel wall stiffness, which are important triggers of arterial hypertension and atherosclerosis. Nevertheless, free fatty acid receptors (FFARs) are involved in the regulation of arterial functions, including the proliferation, differentiation, migration, apoptosis, inflammation, and angiogenesis of vascular endothelial cells (VECs) and vascular smooth muscle cells (VSMCs). They actively regulate hypertension, endothelial dysfunction, and atherosclerosis. The objective of this review is to examine the roles and heterogeneity of FFAs and FFARs in the regulation of arterial function, with a view to identifying the points of intersection between their actions and providing new insights into the prevention and treatment of diseases associated with arterial dysfunction, as well as the development of targeted drugs.
High-Density Lipoprotein Subclasses and Their Role in the Prevention and Treatment of Cardiovascular Disease: A Narrative Review
Authors: Chen Qiaofei , Abudukeremu Ayiguli , Li Kaiwen , Zheng Minglong , Li Hongwei , Huang Tongsheng , Huang Canxia , Wen Kexin , Wang Yue , Zhang Yuling
Published: July 2024

The association between high-density lipoprotein cholesterol (HDL-C) and cardiovascular disease (CVD) is controversial. HDL-C is one content type of high-density lipoprotein (HDL). HDL consists of diverse proteins and lipids and can be classified into different subclasses based on size, shape, charge, and density, and can change dynamically in disease states. Therefore, HDL-C levels alone cannot represent HDLs’ cardioprotective role. In this review, we summarized the methods for separating HDL subclasses, the studies on the association between HDL subclasses and cardiovascular risk (CVR), and the impact of lipid-modifying medications and nonpharmacological approaches (exercise training, dietary omega fatty acids, and low-density lipoprotein apheresis) on HDL subclasses. As HDL is a natural nanoplatform, recombinant HDLs (rHDLs) have been used as a delivery system in vivo by loading small interfering RNA, drugs, contrast agents, etc. Therefore, we further reviewed the HDL subclasses used in rHDLs and their advantages and disadvantages. This review would provide recommendations and guidance for future studies on HDL subclasses’ cardioprotective roles.
Evaluating the Therapeutic Effect of Hispidin on Prostate Cancer Cells
Authors: Chan Kai-Cheng , Basavaraj Praveenkumar , Tsai Jui-Chen , Viehoever Jonathan , Hsieh Bing-Yan , Li Xin-Yu , Huang Guan-Jhong , Huang Wen-Chin
Published: July 2024

Androgen deprivation therapy (ADT) is the primary treatment for advanced prostate cancer (PCa). However, prolonged ADT inevitably results in therapy resistance with the emergence of the castration-resistant PCa phenotype (CRPC). Hence, there is an urgent need to explore new treatment options capable of delaying PCa progression. Hispidin (HPD) is a natural polyketide primarily derived from plants and fungi. HPD has been shown to have a diverse pharmacological profile, exhibiting anti-inflammatory, antiviral, cardiovascular and neuro-protective activities. However, there is currently no research regarding its properties in the context of PCa treatment. This research article seeks to evaluate the anti-cancer effect of HPD and determine the underlying molecular basis in both androgen-sensitive PCa and CRPC cells. Cell growth, migration, and invasion assays were performed via the MTS method, a wound healing assay and the transwell method. To investigate if HPD affected the expression of proteins, Western blot analysis was conducted. Furthermore, apoptosis was assessed by Annexin V-FITC/PI staining and Western blot analyses. HPD exhibited a favorable pharmaceutical profile to inhibit cell growth; disrupt the cell cycle; attenuate wound healing, migration and invasion; and induce apoptosis in PCa cells in vitro. The mechanistic results demonstrated that HPD reduced AR, MMP-2 and MMP-9 expression and activated the caspase-related pathway, leading to programmed cell death in PCa cells. We showed the anti-cancer effect of HPD on PCa cells and confirmed its feasibility as a novel therapeutic agent. This study provides significant insights into the delineation of the molecular mechanism of HPD in PCa cells and the development of an effective and safe therapy using HPD to eliminate PCa progression.
Wrinkle-Improving Effect of Novel Peptide That Binds to Nicotinic Acetylcholine Receptor
Authors: Bang Jinho , Hwang Yul-Lye , Kim Mi Yoon , Yun Jae Nam , Hyun Eujin , Chang Min Youl , Shin Dae Hwan , Kim Sunghyun , Lee Jeung-Hoon
Published: July 2024

Wrinkles, one of the most common signs of aging, are primarily caused by the continuous contraction of muscles. Muscle contraction is induced by the binding of acetylcholine (ACh), released at the neuromuscular junction, to nicotinic acetylcholine receptor (nAChR) present on the muscle cell surface. In this study, we aimed to develop a wrinkle-improving peptide that inhibits the binding of ACh to nAChR using peptide phage display technology. Our peptide showed a remarkably high binding affinity to nAChR subunit α1, with a value below 1 µM, and was found to inhibit the action of ACh through its interaction with these receptors. Furthermore, it increased collagen synthesis in skin cells and upregulated the expression of the aquaporin-3 (AQP3) and hyaluronan synthase-2 (HAS2) genes. These results confirm that the peptide effectively inhibits muscle contraction and enhances skin elasticity and hydration, contributing to its wrinkle-reducing effects. Clinical studies on humans observed significant improvement in wrinkles after three weeks of use, with substantial reduction observed after six weeks. In conclusion, these findings demonstrate the efficacy of the peptide (named Medipep) in reducing wrinkles.
Effects of RF Electric Currents on Hair Follicle Growth and Differentiation: A Possible Treatment for Alopecia
Authors: Martínez-Pascual María Antonia , Sacristán Silvia , Toledano-Macías Elena , Naranjo Pablo , Hernández-Bule María Luisa
Published: July 2024

Androgenic alopecia (AGA) is the most common type of alopecia and its treatments involve drugs that have various adverse effects and are not completely effective. Radiofrequency-based therapies (RF) are an alternative for AGA treatment. Although there is increasing clinical evidence of the effectiveness of RF for alopecia, its effects at the tissue and cellular level have not been studied in detail. The objective of this study was to analyze ex vivo the potential effect of RF currents used in capacitive resistive electrical transfer (CRET) therapy on AGA. Hair follicles (HFs) were donated by patients with AGA and treated with CRET. AGA-HFs were exposed in vitro to intermittent 448 kHz electric current in subthermal conditions. Cell proliferation (Ki67), apoptosis (TUNEL assay), differentiation (β-catenin), integrity (collagen and MMP9), thickness of the epidermis surrounding HF, proportion of bulge cells and melanoblasts in AGA-HF were analyzed by immunohistochemistry. CRET increased proliferation and decreased death of different populations of AGA-HF cells. In addition, the melanoblasts increased in bulge and the epidermis surrounding the hair follicle thickened. These results support the effectiveness of RF-based therapies for the treatment of alopecia. However, clinical trials are necessary to know the true effectiveness of CRET therapy and other RF therapies for AGA treatment.
Fermented Wheat Germ Protein with Histone Deacetylase Inhibitor AR42 Demonstrates Enhanced Cytotoxicity against Lymphoma Cells In Vitro and In Vivo
Authors: Meckler Joshua F. , Levis Daniel J. , Kong Yanguo , O’Donnell Robert T. , Vang Daniel P. , Tuscano Joseph M.
Published: July 2024

Current treatments for lymphoma are plagued by substantial toxicity and the inability to overcome drug resistance, leading to eventual relapse and rationalizing the development of novel, less toxic therapeutics and drug combinations. Histone deacetylase inhibitors (HDACis) are a broad class of epigenetic modulators that have been studied in multiple tumor types, including lymphoma. Currently, HDACis are FDA-approved for treating relapsed T-cell lymphomas and multiple myeloma, with ongoing trials in other lymphomas and solid tumors. As single agents, HDACis frequently elicit toxic side effects and have limited efficacy; therefore, many current treatment strategies focus on combinations to boost efficacy while attempting to minimize toxicity. Fermented wheat germ extract (FWGE) is a complementary agent that has shown efficacy in several malignancies, including lymphoma. Here, we utilize a more potent FWGE derivative, known as fermented wheat germ protein (FWGP), in combination with the HDACi AR42, to assess for enhanced activity. We report increased in vitro killing, cell cycle arrest, and in vivo efficacy for this combination compared to each agent alone with minimal toxicity, suggesting a potentially new, minimally toxic treatment modality for lymphoma.
Discovery of a Therapeutic Agent for Glioblastoma Using a Systems Biology-Based Drug Repositioning Approach
Authors: Kaynar Ali , Ozcan Mehmet , Li Xiangyu , Turkez Hasan , Zhang Cheng , Uhlén Mathias , Shoaie Saeed , Mardinoglu Adil
Published: July 2024

Glioblastoma (GBM), a highly malignant tumour of the central nervous system, presents with a dire prognosis and low survival rates. The heterogeneous and recurrent nature of GBM renders current treatments relatively ineffective. In our study, we utilized an integrative systems biology approach to uncover the molecular mechanisms driving GBM progression and identify viable therapeutic drug targets for developing more effective GBM treatment strategies. Our integrative analysis revealed an elevated expression of CHST2 in GBM tumours, designating it as an unfavourable prognostic gene in GBM, as supported by data from two independent GBM cohorts. Further, we pinpointed WZ-4002 as a potential drug candidate to modulate CHST2 through computational drug repositioning. WZ-4002 directly targeted EGFR (ERBB1) and ERBB2, affecting their dimerization and influencing the activity of adjacent genes, including CHST2. We validated our findings by treating U-138 MG cells with WZ-4002, observing a decrease in CHST2 protein levels and a reduction in cell viability. In summary, our research suggests that the WZ-4002 drug candidate may effectively modulate CHST2 and adjacent genes, offering a promising avenue for developing efficient treatment strategies for GBM patients.
Comparative Analysis of Plastome Sequences of Seven Tulipa L. (Liliaceae Juss.) Species from Section Kolpakowskianae Raamsd. Ex Zonn and Veldk.
Authors: Almerekova Shyryn , Yermagambetova Moldir , Ivaschenko Anna , Turuspekov Yerlan , Abugalieva Saule
Published: July 2024

Tulipa L. is a genus of significant economic, environmental, and cultural importance in several parts of the world. The exact number of species in the genus remains uncertain due to inherent taxonomic challenges. We utilized next-generation sequencing technology to sequence and assemble the plastid genomes of seven Tulipa species collected in Kazakhstan and conducted a comparative analysis. The total number of annotated genes was 136 in all seven studied Tulipa species, 114 of which were unique, including 80 protein-coding, 30 tRNA, and 4 rRNA genes. Nine regions (petD, ndhH, ycf2-ycf3, ndhA, rpl16, clpP, ndhD-ndhF, rpoC2, and ycf1) demonstrated significant nucleotide variability, suggesting their potential as molecular markers. A total of 1388 SSRs were identified in the seven Tulipa plastomes, with mononucleotide repeats being the most abundant (60.09%), followed by dinucleotide (34.44%), tetranucleotide (3.90%), trinucleotide (1.08%), pentanucleotide (0.22%), and hexanucleotide (0.29%). The Ka/Ks values of the protein-coding genes ranged from 0 to 3.9286, with the majority showing values <1. Phylogenetic analysis based on a complete plastid genome and protein-coding gene sequences divided the species into three major clades corresponding to their subgenera. The results obtained in this study may contribute to understanding the phylogenetic relationships and molecular taxonomy of Tulipa species.
Disruption of Cell Membranes and Redox Homeostasis as an Antibacterial Mechanism of Dielectric Barrier Discharge Plasma against Fusarium oxysporum
Authors: Yu Shiqian , Sun Jiajin , Chen Haiming , Chen Weijun , Zhong Qiuping , Zhang Ming , Pei Jianfei , He Rongrong , Chen Wenxue
Published: July 2024

Direct barrier discharge (DBD) plasma is a potential antibacterial strategy for controlling Fusarium oxysporum (F. oxysporum) in the food industry. The aim of this study was to investigate the inhibitory effect and mechanism of action of DBD plasma on F. oxysporum. The result of the antibacterial effect curve shows that DBD plasma has a good inactivation effect on F. oxysporum. The DBD plasma treatment severely disrupted the cell membrane structure and resulted in the leakage of intracellular components. In addition, flow cytometry was used to observe intracellular reactive oxygen species (ROS) levels and mitochondrial membrane potential, and it was found that, after plasma treatment, intracellular ROS accumulation and mitochondrial damage were accompanied by a decrease in antioxidant enzyme activity. The results of free fatty acid metabolism indicate that the saturated fatty acid content increased and unsaturated fatty acid content decreased. Overall, the DBD plasma treatment led to the oxidation of unsaturated fatty acids, which altered the cell membrane fatty acid content, thereby inducing cell membrane damage. Meanwhile, DBD plasma-induced ROS penetrated the cell membrane and accumulated intracellularly, leading to the collapse of the antioxidant system and ultimately causing cell death. This study reveals the bactericidal effect and mechanism of the DBD treatment on F. oxysporum, which provides a possible strategy for the control of F. oxysporum.
Ruthenium(II) Complex-Based Tetradentate Schiff Bases: Synthesis, Spectroscopic, Antioxidant, and Antibacterial Investigations
Authors: Es-Sounni Bouchra , Harboul Kaoutar , Mouhib Ayoub , Alanazi Ashwag S. , Hefnawy Mohamed , Bakhouch Mohamed , Benali Taoufiq , Hammani Khalil , Mazoir Noureddine , El Yazidi Mohamed , Benharref Ahmed , Fahim Mohammed
Published: July 2024

In this work, we describe the synthesis of novel Ruthenium (II) complex-based salen Schiff bases. The obtained Ruthenium (II) complexes are characterized using usual spectroscopic and spectrometric techniques, viz., IR, UV-Vis, NMR (1H and 13C), powder X-ray diffraction, and HRMS. Further techniques, such as DTA-TGA and elemental analysis, are used to well establish the structure of the obtained complexes. Octahedral geometries are tentatively proposed for the new Ru(II) complexes. The measured molar conductance for the Ruthenium (II) complexes shows their electrolytic nature (4.24–4.44 S/m). The new Ru(II) complexes are evaluated for their antioxidant and antibacterial activities. The DPPH radical scavenging, FRAP, and total antioxidant capacity (TAC) assays show that the obtained complexes are more potent than the used positive control. They also exhibit promising antibacterial responses against pathogen bacteria: [RuH2L3Cl2] exhibits an important inhibition against Bacillus subtilis DSM 6633, with an inhibition zone of 21 ± 1.41 mm with an MIC value of 0.39 mg/mL, and Proteus mirabilis INH, with 16.50 ± 0.70 mm and an MIC value of 0.78 mg/mL, while [RuH2L2Cl2] exerts interesting antibacterial effects versus Bacillus subtilis DSM 6633 (21 ± 1.41 mm) and Proteus mirabilis INH (25.5 ± 0.70 mm) with equal MIC values of 0.97 mg/mL.
Metabolic Derangement of Essential Transition Metals and Potential Antioxidant Therapies
Authors: Fontes Adriana , Jauch Adrian T. , Sailer Judith , Engler Jonas , Azul Anabela Marisa , Zischka Hans
Published: July 2024

Essential transition metals have key roles in oxygen transport, neurotransmitter synthesis, nucleic acid repair, cellular structure maintenance and stability, oxidative phosphorylation, and metabolism. The balance between metal deficiency and excess is typically ensured by several extracellular and intracellular mechanisms involved in uptake, distribution, and excretion. However, provoked by either intrinsic or extrinsic factors, excess iron, zinc, copper, or manganese can lead to cellular damage upon chronic or acute exposure, frequently attributed to oxidative stress. Intracellularly, mitochondria are the organelles that require the tightest control concerning reactive oxygen species production, which inevitably leaves them to be one of the most vulnerable targets of metal toxicity. Current therapies to counteract metal overload are focused on chelators, which often cause secondary effects decreasing patients’ quality of life. New therapeutic options based on synthetic or natural antioxidants have proven positive effects against metal intoxication. In this review, we briefly address the cellular metabolism of transition metals, consequences of their overload, and current therapies, followed by their potential role in inducing oxidative stress and remedies thereof.
A Biosensor for Simultaneous Detection of Epinephrine and Ascorbic Acid Based on Fe(III)–Polyhistidine-Functionalized Multi-Wall Carbon Nanotube Composites
Authors: Han Bingkai , Chen Yuan , Wang Hongtao , Yan Jilong , Liu Guang , Huang Ziru , Zhou Chenghang
Published: July 2024

Epinephrine (EP) is a very important chemical transmitter in the transmission of nerve impulses in the central nervous system of mammals. Ascorbic acid (AA) is considered to be the most important extracellular fluid antioxidant and has important antioxidant properties in the cell. In this study, a series of transition metal–polyhistidine-carboxylated multi-wall carbon nanotube nanocomposites were synthesized, and their simultaneous catalytic effects on epinephrine and ascorbic acid were investigated. The results showed that nanocomposites based on iron ions had the highest catalytic activity. The prepared biosensor expressed high selectivity toward EP and AA with LOD values of 0.1 μΜ (AA) and 0.01 μΜ (EP), and sensitivity values of 4.18 μA mM−1 with a range of 0.001–5 mM (AA), 50.98 μA mM−1 with a range of 0.2–100 μM (EP), and 265.75 μA mM−1 with a range of 0.1–1.0 mM (EP). Moreover, it showed good stability, good repeatability and high selectivity in real sample detection. This work is a reference for the design of new electrochemical enzyme-free biosensors and the detection of biomarkers.
The Protective Role of Molecular Hydrogen in Ischemia/Reperfusion Injury
Authors: Kura Branislav , Slezak Jan
Published: July 2024

Ischemia/reperfusion injury (IRI) represents a significant contributor to morbidity and mortality associated with various clinical conditions, including acute coronary syndrome, stroke, and organ transplantation. During ischemia, a profound hypoxic insult develops, resulting in cellular dysfunction and tissue damage. Paradoxically, reperfusion can exacerbate this injury through the generation of reactive oxygen species and the induction of inflammatory cascades. The extensive clinical sequelae of IRI necessitate the development of therapeutic strategies to mitigate its deleterious effects. This has become a cornerstone of ongoing research efforts in both basic and translational science. This review examines the use of molecular hydrogen for IRI in different organs and explores the underlying mechanisms of its action. Molecular hydrogen is a selective antioxidant with anti-inflammatory, cytoprotective, and signal-modulatory properties. It has been shown to be effective at mitigating IRI in different models, including heart failure, cerebral stroke, transplantation, and surgical interventions. Hydrogen reduces IRI via different mechanisms, like the suppression of oxidative stress and inflammation, the enhancement of ATP production, decreasing calcium overload, regulating cell death, etc. Further research is still needed to integrate the use of molecular hydrogen into clinical practice.
Behind the Curtain of Abnormal Placentation in Pre-Eclampsia: From Molecular Mechanisms to Histological Hallmarks
Authors: Gusella Anna , Martignoni Guido , Giacometti Cinzia
Published: July 2024

Successful human pregnancy needs several highly controlled steps to guarantee an oocyte’s fertilization, the embryo’s pre-implantation development, and its subsequent implantation into the uterine wall. The subsequent placenta development ensures adequate fetal nutrition and oxygenation, with the trophoblast being the first cell lineage to differentiate during this process. The placenta sustains the growth of the fetus by providing it with oxygen and nutrients and removing waste products. It is not surprising that issues with the early development of the placenta can lead to common pregnancy disorders, such as recurrent miscarriage, fetal growth restriction, pre-eclampsia, and stillbirth. Understanding the normal development of the human placenta is essential for recognizing and contextualizing any pathological aberrations that may occur. The effects of these issues may not become apparent until later in pregnancy, during the mid or advanced stages. This review discusses the process of the embryo implantation phase, the molecular mechanisms involved, and the abnormalities in those mechanisms that are thought to contribute to the development of pre-eclampsia. The review also covers the histological hallmarks of pre-eclampsia as found during the examination of placental tissue from pre-eclampsia patients.
NATCA YOLO-Based Small Object Detection for Aerial Images
Authors: Zhu Yicheng , Ai Zhenhua , Yan Jinqiang , Li Silong , Yang Guowei , Yu Teng
Published: July 2024

The object detection model in UAV aerial image scenes faces challenges such as significant scale changes of certain objects and the presence of complex backgrounds. This paper aims to address the detection of small objects in aerial images using NATCA (neighborhood attention Transformer coordinate attention) YOLO. Specifically, the feature extraction network incorporates a neighborhood attention transformer (NAT) into the last layer to capture global context information and extract diverse features. Additionally, the feature fusion network (Neck) incorporates a coordinate attention (CA) module to capture channel information and longer-range positional information. Furthermore, the activation function in the original convolutional block is replaced with Meta-ACON. The NAT serves as the prediction layer in the new network, which is evaluated using the VisDrone2019-DET object detection dataset as a benchmark, and tested on the VisDrone2019-DET-test-dev dataset. To assess the performance of the NATCA YOLO model in detecting small objects in aerial images, other detection networks, such as Faster R-CNN, RetinaNet, and SSD, are employed for comparison on the test set. The results demonstrate that the NATCA YOLO detection achieves an average accuracy of 42%, which is a 2.9% improvement compared to the state-of-the-art detection network TPH-YOLOv5.
An Open Data-Based Omnichannel Approach for Personalized Healthcare
Authors: Moreira Ailton , Santos Manuel Filipe
Published: July 2024

Currently, telemedicine and telehealth have grown, prompting healthcare institutions to seek innovative ways to incorporate them into their services. Challenges such as resource allocation, system integration, and data compatibility persist in healthcare. Utilizing an open data approach in a versatile mobile platform holds great promise for addressing these challenges. This research focuses on adopting such an approach for a mobile platform catering to personalized care services. It aims to bridge identified gaps in healthcare, including fragmented communication channels and limited real-time data access, through an open data approach. This study builds upon previous research in omnichannel healthcare using prototyping to design a mobile companion for personalized care. By combining an omnichannel mobile companion with open data principles, this research successfully tackles key healthcare gaps, enhancing patient-centered care and improving data accessibility and integration. The strategy proves effective despite encountering challenges, although additional issues in personalized care services warrant further exploration and consideration.
Investigating the Ability of Road Specifications to Discriminate the Rutting Behavior of Rubberized Asphalt Mixtures in Italy
Authors: Ghani Usman , Milazzo Silvia , Giancontieri Gaspare , Buttitta Gabriella , Gu Fan , Presti Davide Lo
Published: July 2024

Despite its worldwide adoption in many countries, rubberized asphalt mixtures are not fully incorporated as an alternative paving material in current Italian road specifications. This reluctance stems from a lack of experience, resistance to change in established work practices, and, sometimes, insufficient evidence demonstrating tangible benefits with local specifications. Furthermore, conventional characterization methods such as void checks and indirect tensile strength testing by means of IDT may not accurately capture the true benefits of using alternative paving materials. This study introduces performance-driven characterization approaches with the final aim of evaluating whether more advanced procedures may provide additional information compared to current practices and, in turn, promote the use of alternative paving materials. Hence, an investigation has been conducted to compare the rutting behavior of conventional asphalt mixtures with those modified with engineered crumb rubber (ECR). This comparison utilized performance-driven characterization approaches, including a basic IDT-based methodology at higher temperatures (HT-IDT), as well as two more sophisticated approaches, the Stress Sweep Rutting (SSR) and Flow Number (FN) tests, using the asphalt mixture performance tester (AMPT). Finally, the results were compared with those obtained using the IDT, a conventional method as specified by the major Italian road authority. As a result, the addition of ECR proves beneficial in enhancing the qualities of dense mixtures tailored for use on urban and secondary roads; however, only performance-driven characterization, with both basic and advanced methodologies, can clearly describe the pivotal role of ECR in achieving discernible enhancements in the rutting behavior of asphalt mixtures.
Success Factors and Partnership Evaluation of Air–Rail Integration Development: A Case of a High-Speed Rail Project Linking Three Airports in Thailand
Authors: Rattanakijsuntorn Waralee , Suwannarat Benyapa , Samittivate Nitchamol , Nithikittiwat Chanuwat
Published: July 2024

As the air–rail integration continues to emerge around the globe, the successful and maintainable implementation of such schemes can be influenced by many factors within administrative, social, infrastructural, and economic aspects. With the existing airport rail link system that shifted from air–rail integration at beginning to air–rail cooperation at present, this work aims to assess the success factors of air–rail integration development in Thailand and evaluate the partnership level required to achieve a long-term and indefinite horizon of relationship based on an ongoing airport rail link project in the country. The factor assessment results from using fuzzy analytical hierarchy process (AHP) revealed different perspectives from regulators and operators, while directing the high influence of administrative, economic, and infrastructural factors. The partnership evaluation suggested the highest level of partnership; although, the operators still express doubt whether the competitive advantages incurred from the partnership and the partnership itself would be sustainable.
Acoustic Communication in Dendroctonus adjunctus Blandford (Curculionidae Scolytinae): Description of Calls and Sound Production Mechanism
Authors: Cerrillo-Mancilla León L. , Cano-Ramírez Claudia , Zúñiga Gerardo
Published: July 2024

The acoustic communication system (ACS) in bark beetles has been studied mainly in species of the genera Dendroctonus, Ips and Polygraphus. Specifically, ACS of the roundheaded pine beetle, Dendroctonus adjunctus, has been little studied. In this study, we described the stridulatory apparatus of this beetle using optical and scanning electron microscopy and recorded the call types produced by males in three behavioral contexts: stress, female–male–, and male–male interactions. From the spectrograms and waveforms, call types, as well as temporal (tooth strike, tooth strike rate, and intertooth strike interval) and spectral features (minimum, maximum and dominant frequency), were determined. Males have a functional elytro–tergal stridulatory apparatus—females do not—consisting of a file for the pars stridens and two lobes for the plectrum. Most of spectro–temporal features were statistically different between single– and multi–noted calls and across the three behavioral contexts. In the male–male interaction, a new type of call named “withdrawal” was produced by the male withdrawing or fleeing. Our results suggest that the spectro–temporal features of single– and multiple–noted calls in the three behavioral conditions are specific and different from each other. Yet, the combination of single and multiple calls determines an overall calling pattern characteristic of the tested behaviors and, therefore, is species–specific.
Advances in Non-Small Cell Lung Cancer: Current Insights and Future Directions
Authors: Garg Pankaj , Singhal Sulabh , Kulkarni Prakash , Horne David , Malhotra Jyoti , Salgia Ravi , Singhal Sharad S.
Published: July 2024

The leading cause of cancer deaths worldwide is attributed to non-small cell lung cancer (NSCLC), necessitating a continual focus on improving the diagnosis and treatment of this disease. In this review, the latest breakthroughs and emerging trends in managing NSCLC are highlighted. Major advancements in diagnostic methods, including better imaging technologies and the utilization of molecular biomarkers, are discussed. These advancements have greatly enhanced early detection and personalized treatment plans. Significant improvements in patient outcomes have been achieved by new targeted therapies and immunotherapies, providing new hope for individuals with advanced NSCLC. This review discusses the persistent challenges in accessing advanced treatments and their associated costs despite recent progress. Promising research into new therapies, such as CAR-T cell therapy and oncolytic viruses, which could further revolutionize NSCLC treatment, is also highlighted. This review aims to inform and inspire continued efforts to improve outcomes for NSCLC patients globally, by offering a comprehensive overview of the current state of NSCLC treatment and future possibilities.
Real-World Safety Profile of Biologic Drugs for Severe Uncontrolled Asthma: A Descriptive Analysis from the Spanish Pharmacovigilance Database
Authors: Boada-Fernández-del-Campo Carlos , García-Sánchez-Colomer Marcelino , Fernández-Quintana Eduardo , Poza-Guedes Paloma , Rolingson-Landaeta Jaime Leonardo , Sánchez-Machín Inmaculada , González-Pérez Ruperto
Published: July 2024

Background: The present investigation provides a thorough analysis of adverse drug reactions (ADRs) reported in the Database of the Spanish Pharmacovigilance System (FEDRA) for biologic medications primarily indicated for severe refractory asthma, including omalizumab, mepolizumab, reslizumab, benralizumab, dupilumab, and tezepelumab. Our main objective was to identify ADRs not documented in the drugs’ Technical Sheets (summary of product characteristics, SmPC), potentially indicating unrecognized risks meriting pharmacovigilance attention. Methods: Data spanning from each drug’s market introduction until 22 January 2024, were analyzed, sourced from direct submissions to the Spanish Pharmacovigilance System, industry communications, and literature reviews. We evaluated notifications impartially to ensure a comprehensive review of all the ADRs associated with these medications. Results: This investigation underlines the critical role of post-marketing surveillance in enhancing patient safety. It emphasizes the necessity for healthcare professionals to report ADRs comprehensively to foster a robust pharmacovigilance system. Furthermore, the study highlights gaps between the reported ADRs and the information provided in SmPCs, signaling potential areas for improvement in drug safety monitoring and regulatory oversight. Conclusions: Finally, these findings may contribute to informed decision making in clinical practice and regulatory policy, ultimately advancing patient care and safety in the management of severe uncontrolled asthma.
Does Patellar Height Influence Range of Motion and Anterior Knee Pain after Distal Femur Endoprosthesis Reconstruction?
Authors: Sambri Andrea , Paganelli Chiara , Parisi Stefania Claudia , Filippini Matteo , Cevolani Luca , Stimolo Davide , Bortoli Marta , Guarino Andrea , Bruschi Alessandro , Fiore Michele , Campanacci Domenico Andrea , Donati Davide Maria , De Paolis Massimiliano
Published: July 2024

Objectives: This study aims to evaluate the patellar height changes after distal femur (DF) endoprosthetic replacement (EPR) and its impact on anterior knee pain (AKP) and range of motion (ROM). Methods: A retrospective review of three institutions’ databases was performed. The patellar height was determined using the modified Insall–Salvati ratio (MIS), the Blackburne–Peel (BP) and the Caton–Deschamps (CD) indexes. Data regarding AKP and ROM were collected. Results: A total of 199 patients were included. The mean age at presentation was 37.9 ± 23.1 years. The mean one-year follow-up MIS, BP and CD were 1.52 (sd: 0.41), 0.82 (sd: 0.33) and 0.93 (sd: 0.33). Patellar height decreased significantly compared to the pre-operative values according to all three scores (p < 0.001). AKP was reported by 34 (17.1%) patients at 1 year follow-up. Patients with patella baja (MIS < 1.2) or pseudo patella baja (CD < 0.6) had a higher incidence of AKP (p = 0.037 and p = 0.024, respectively). The mean flexion ROM was 91°, with a direct correlation with patellar height (MIS p = 0.020, BP p = 0.036 and CD p = 0.036). Conclusion: The restoration of the native position of the joint line in DF EPR is important to maintain optimal patellofemoral biomechanics. Despite surgeons’ tendency toward a reduction in patellar height with respect to pre-operative values, an increase in patellar height might help to achieve better knee flexion and reduce AKP.
Cutting Periprosthetic Infection Rate: Staphylococcus aureus Decolonization as a Mandatory Procedure in Preoperative Knee and Hip Replacement Care—Insights from a Systematic Review and Meta-Analysis of More Than 50,000 Patients
Authors: Bianco Prevot Luca , Tansini Luca , Riccardo Accetta , Bolcato Vittorio , Tronconi Livio Pietro , Basile Giuseppe
Published: July 2024

Background: No consensus in the literature has been found about the necessity of implementing a decolonization screening protocol for Staphylococcus aureus in patients who undergo prosthesis implantation of the knee (TKA) or of the hip (THA), with the aim of reducing periprosthetic infections (PJIs). Methods: A systematic literature search was conducted using PubMed, Web of Science, and Embase in April 2024. Studies conducted on patients who underwent a TKA or THA and who followed a screening and decolonization protocol from S. aureus were included. The benefits of implementing this protocol were evaluated through the number of infections overall caused by S. aureus and other pathogens. The risk of bias and quality of evidence were assessed using Cochrane guidelines. Results: A total of 922 articles were evaluated, and of these, 12 were included in the study for a total of 56,930 patients. The results of the meta-analysis showed a reduced risk of overall PJI (p = 0.002), PJI caused by S. aureus (p < 0.0001), and PJI caused by MRSA (p < 0.0001) and highlighted no differences between the two groups in the onset of a PJI caused by other bacteria (p = 0.50). Conclusions: This study showed that the screening and decolonization of S. aureus in patients undergoing THA or THA procedures reduced the risk of a PJI. The screening and decolonization protocol for this kind of patient represents an important procedure for the safety of the patient and in social-economic and medico-legal terms.