bluuebunny/crossref_metadata_2025 huggingface dataset:
Normoxic Management during Cardiopulmonary Bypass Does Not Reduce Cerebral Mitochondrial Dysfunction in Neonatal Swine
Authors: Aronowitz Danielle I. , Geoffrion Tracy R. , Piel Sarah , Morton Sarah R. , Starr Jonathan , Melchior Richard W. , Gaudio Hunter A. , Degani Rinat , Widmann Nicholas J. , Weeks M. Katie , Ranieri Nicolina R. , Benson Emilie , Ko Tiffany S. , Licht Daniel J. , Hefti Marco , Gaynor J. William , Kilbaugh Todd J. , Mavroudis Constantine D.
Published: May 2024

Optimal oxygen management during pediatric cardiopulmonary bypass (CPB) is unknown. We previously demonstrated an increase in cortical mitochondrial reactive oxygen species and decreased mitochondrial function after CPB using hyperoxic oxygen management. This study investigates whether controlled oxygenation (normoxia) during CPB reduces cortical mitochondrial dysfunction and oxidative injury. Ten neonatal swine underwent three hours of continuous CPB at 34 °C (flow > 100 mL/kg/min) via cervical cannulation targeting a partial pressure of arterial oxygen (PaO2) goal < 150 mmHg (normoxia, n = 5) or >300 mmHg (hyperoxia, n = 5). The animals underwent continuous hemodynamic monitoring and serial arterial blood sampling. Cortical microdialysate was serially sampled to quantify the glycerol concentration (represents neuronal injury) and lactate-to-pyruvate ratio (represents bioenergetic dysfunction). The cortical tissue was analyzed via high-resolution respirometry to quantify mitochondrial oxygen consumption and reactive oxygen species generation, and cortical oxidized protein carbonyl concentrations were quantified to assess for oxidative damage. Serum PaO2 was higher in hyperoxia animals throughout CPB (p < 0.001). There were no differences in cortical glycerol concentration between groups (p > 0.2). The cortical lactate-to-pyruvate ratio was modestly elevated in hyperoxia animals (p < 0.03) but the values were not clinically significant (<30). There were no differences in cortical mitochondrial respiration (p = 0.48), protein carbonyls (p = 0.74), or reactive oxygen species generation (p = 0.93) between groups. Controlled oxygenation during CPB does not significantly affect cortical mitochondrial function or oxidative injury in the acute setting. Further evaluation of the short and long-term effects of oxygen level titration during pediatric CPB on cortical tissue and other at-risk brain regions are needed, especially in the presence of cyanosis.
Exploiting Cell-Based Assays to Accelerate Drug Development for G Protein-Coupled Receptors
Authors: Wu Yuxin , Jensen Niels , Rossner Moritz J. , Wehr Michael C.
Published: May 2024

G protein-coupled receptors (GPCRs) are relevant targets for health and disease as they regulate various aspects of metabolism, proliferation, differentiation, and immune pathways. They are implicated in several disease areas, including cancer, diabetes, cardiovascular diseases, and mental disorders. It is worth noting that about a third of all marketed drugs target GPCRs, making them prime pharmacological targets for drug discovery. Numerous functional assays have been developed to assess GPCR activity and GPCR signaling in living cells. Here, we review the current literature of genetically encoded cell-based assays to measure GPCR activation and downstream signaling at different hierarchical levels of signaling, from the receptor to transcription, via transducers, effectors, and second messengers. Singleplex assay formats provide one data point per experimental condition. Typical examples are bioluminescence resonance energy transfer (BRET) assays and protease cleavage assays (e.g., Tango or split TEV). By contrast, multiplex assay formats allow for the parallel measurement of multiple receptors and pathways and typically use molecular barcodes as transcriptional reporters in barcoded assays. This enables the efficient identification of desired on-target and on-pathway effects as well as detrimental off-target and off-pathway effects. Multiplex assays are anticipated to accelerate drug discovery for GPCRs as they provide a comprehensive and broad identification of compound effects.
Molecular Characterization and Inhibition of a Novel Stress-Induced Mitochondrial Protecting Role for Misfolded TrkAIII in Human SH-SY5Y Neuroblastoma Cells
Authors: Cappabianca Lucia , Ruggieri Marianna , Sebastiano Michela , Sbaffone Maddalena , Martelli Ilaria , Ruggeri Pierdomenico , Di Padova Monica , Farina Antonietta Rosella , Mackay Andrew Reay
Published: May 2024

Pediatric neuroblastomas (NBs) are heterogeneous, aggressive, therapy-resistant embryonal tumors that originate from cells of neural crest origin committed to the sympathoadrenal progenitor cell lineage. Stress- and drug-resistance mechanisms drive post-therapeutic relapse and metastatic progression, the characterization and inhibition of which are major goals in improving therapeutic responses. Stress- and drug-resistance mechanisms in NBs include alternative TrkAIII splicing of the neurotrophin receptor tropomyosin-related kinase A (NTRK1/TrkA), which correlates with post-therapeutic relapse and advanced-stage metastatic disease. The TrkAIII receptor variant exerts oncogenic activity in NB models by mechanisms that include stress-induced mitochondrial importation and activation. In this study, we characterize novel targetable and non-targetable participants in this pro-survival mechanism in TrkAIII-expressing SH-SY5Y NB cells, using dithiothreitol (DTT) as an activator and a variety of inhibitors by regular and immunoprecipitation Western blotting of purified mitochondria and IncuCyte cytotoxicity assays. We report that stress-induced TrkAIII misfolding initiates this mechanism, resulting in Grp78, Ca2+-calmodulin, adenosine ribosylating factor (Arf) and Hsp90-regulated mitochondrial importation. TrkAIII imported into inner mitochondrial membranes is cleaved by Omi/high temperature requirement protein A2 (HtrA2) then activated by a mechanism dependent upon calmodulin kinase II (CaMKII), alpha serine/threonine kinase (Akt), mitochondrial Ca2+ uniporter and reactive oxygen species (ROS), involving inhibitory mitochondrial protein tyrosine phosphatase (PTPase) oxidation, resulting in phosphoinositide 3 kinase (PI3K) activation of mitochondrial Akt, which enhances stress resistance. This novel pro-survival function for misfolded TrkAIII mitigates the cytotoxicity of mitochondrial Ca2+ homeostasis disrupted during integrated stress responses, and is prevented by clinically approved Trk and Akt inhibitors and also by inhibitors of 78kDa glucose regulated protein (Grp78), heat shock protein 90 (Hsp90), Ca2+-calmodulin and PI3K. This identifies Grp78, Ca2+-calmodulin, Hsp90, PI3K and Akt as novel targetable participants in this mechanism, in addition to TrkAIII, the inhibition of which has the potential to enhance the stress-induced elimination of TrkAIII-expressing NB cells, with the potential to improve therapeutic outcomes in NBs that exhibit TrkAIII expression and activation.
N-3 Polyunsaturated Fatty Acids Protect against Alcoholic Liver Steatosis by Activating FFA4 in Kupffer Cells
Authors: Kang Saeromi , Koh Jung-Min , Im Dong-Soon
Published: May 2024

Supplementation with fish oil rich in omega-3 polyunsaturated fatty acids (n-3 PUFAs) effectively reduces acute and chronic alcohol-induced hepatic steatosis. We aimed to find molecular mechanisms underlying the effects of n-3 PUFAs in alcohol-induced hepatic steatosis. Because free fatty acid receptor 4 (FFA4, also known as GPR120) has been found as a receptor for n-3 PUFAs in an ethanol-induced liver steatosis model, we investigated whether n-3 PUFAs protect against liver steatosis via FFA4 using AH7614, an FFA4 antagonist, and Ffa4 knockout (KO) mice. N-3 PUFAs and compound A (CpdA), a selective FFA4 agonist, reduced the ethanol-induced increase in lipid accumulation in hepatocytes, triglyceride content, and serum ALT levels, which were not observed in Ffa4 KO mice. N-3 PUFAs and CpdA also reduced the ethanol-induced increase in lipogenic sterol regulatory element-binding protein-1c expression in an FFA4-dependent manner. In Kupffer cells, treatment with n-3 PUFA and CpdA reversed the ethanol-induced increase in tumor necrosis factor-α, cyclooxygenase-2, and NLR family pyrin domain-containing 3 expression levels in an FFA4-dependent manner. In summary, n-3 PUFAs protect against ethanol-induced hepatic steatosis via the anti-inflammatory actions of FFA4 on Kupffer cells. Our findings suggest FFA4 as a therapeutic target for alcoholic hepatic steatosis.
Initial Despair and Current Hope of Identifying a Clinically Useful Treatment of Myocardial Reperfusion Injury: Insights Derived from Studies of Platelet P2Y12 Antagonists and Interference with Inflammation and NLRP3 Assembly
Authors: Cohen Michael V. , Downey James M.
Published: May 2024

Myocardial necrosis following the successful reperfusion of a coronary artery occluded by thrombus in a patient presenting with ST-elevation myocardial infarction (STEMI) continues to be a serious problem, despite the multiple attempts to attenuate the necrosis with agents that have shown promise in pre-clinical investigations. Possible reasons include confounding clinical risk factors, the delayed application of protective agents, poorly designed pre-clinical investigations, the possible effects of routinely administered agents that might unknowingly already have protected the myocardium or that might have blocked protection, and the biological differences of the myocardium in humans and experimental animals. A better understanding of the pathobiology of myocardial infarction is needed to stem this reperfusion injury. P2Y12 receptor antagonists minimize platelet aggregation and are currently part of the standard treatment to prevent thrombus formation and propagation in STEMI protocols. Serendipitously, these P2Y12 antagonists also dramatically attenuate reperfusion injury in experimental animals and are presumed to provide a similar protection in STEMI patients. However, additional protective agents are needed to further diminish reperfusion injury. It is possible to achieve additive protection if the added intervention protects by a mechanism different from that of P2Y12 antagonists. Inflammation is now recognized to be a critical factor in the complex intracellular response to ischemia and reperfusion that leads to tissue necrosis. Interference with cardiomyocyte inflammasome assembly and activation has shown great promise in attenuating reperfusion injury in pre-clinical animal models. And the blockade of the executioner protease caspase-1, indeed, supplements the protection already seen after the administration of P2Y12 antagonists. Importantly, protective interventions must be applied in the first minutes of reperfusion, if protection is to be achieved. The promise of such a combination of protective strategies provides hope that the successful attenuation of reperfusion injury is attainable.
Inhibition of ERK1/2 or CRMP2 Disrupts Alcohol Memory Reconsolidation and Prevents Relapse in Rats
Authors: Rahamim Nofar , Liran Mirit , Aronovici Coral , Flumin Hila , Gordon Tamar , Urshansky Nataly , Barak Segev
Published: May 2024

Relapse to alcohol abuse, often caused by cue-induced alcohol craving, is a major challenge in alcohol addiction treatment. Therefore, disrupting the cue-alcohol memories can suppress relapse. Upon retrieval, memories transiently destabilize before they reconsolidate in a process that requires protein synthesis. Evidence suggests that the mammalian target of rapamycin complex 1 (mTORC1), governing the translation of a subset of dendritic proteins, is crucial for memory reconsolidation. Here, we explored the involvement of two regulatory pathways of mTORC1, phosphoinositide 3-kinase (PI3K)-AKT and extracellular regulated kinase 1/2 (ERK1/2), in the reconsolidation process in a rat (Wistar) model of alcohol self-administration. We found that retrieval of alcohol memories using an odor-taste cue increased ERK1/2 activation in the amygdala, while the PI3K-AKT pathway remained unaffected. Importantly, ERK1/2 inhibition after alcohol memory retrieval impaired alcohol-memory reconsolidation and led to long-lasting relapse suppression. Attenuation of relapse was also induced by post-retrieval administration of lacosamide, an inhibitor of collapsin response mediator protein-2 (CRMP2)—a translational product of mTORC1. Together, our findings indicate the crucial role of ERK1/2 and CRMP2 in the reconsolidation of alcohol memories, with their inhibition as potential treatment targets for relapse prevention.
Measurement and Characterization of the Electrical Properties of Actin Filaments
Authors: Paladini Serena , Truglia Barbara , Shankar Karthik , Tuszynski Jack Adam
Published: May 2024

Actin filaments, as key components of the cytoskeleton, have aroused great interest due to their numerous functional roles in eukaryotic cells, including intracellular electrical signaling. The aim of this research is to characterize the alternating current (AC) conduction characteristics of both globular and polymerized actin and quantitatively compare their values to those theoretically predicted earlier. Actin filaments have been demonstrated to act as conducting bionanowires, forming a signaling network capable of transmitting ionic waves in cells. We performed conductivity measurements for different concentrations of actin, considering both unpolymerized and polymerized actin to identify potential differences in their electrical properties. These measurements revealed two relevant characteristics: first, the polymerized actin, arranged in filaments, has a lower impedance than its globular counterpart; second, an increase in the actin concentration leads to higher conductivities. Furthermore, from the data collected, we developed a quantitative model to represent the electrical properties of actin in a buffer solution. We hypothesize that actin filaments can be modeled as electrical resistor–inductor–capacitor (RLC) circuits, where the resistive contribution is due to the viscous ion flows along the filaments; the inductive contribution is due to the solenoidal flows along and around the helix-shaped filament and the capacitive contribution is due to the counterion layer formed around each negatively charged filament.
Vaccines and Monoclonal Antibodies as Alternative Strategies to Antibiotics to Fight Antimicrobial Resistance
Authors: La Guidara Chiara , Adamo Roberto , Sala Claudia , Micoli Francesca
Published: May 2024

Antimicrobial resistance (AMR) is one of the most critical threats to global public health in the 21st century, causing a large number of deaths every year in both high-income and low- and middle-income countries. Vaccines and monoclonal antibodies can be exploited to prevent and treat diseases caused by AMR pathogens, thereby reducing antibiotic use and decreasing selective pressure that favors the emergence of resistant strains. Here, differences in the mechanism of action and resistance of vaccines and monoclonal antibodies compared to antibiotics are discussed. The state of the art for vaccine technologies and monoclonal antibodies are reviewed, with a particular focus on approaches validated in clinical studies. By underscoring the scope and limitations of the different emerging technologies, this review points out the complementary of vaccines and monoclonal antibodies in fighting AMR. Gaps in antigen discovery for some pathogens, as well as challenges associated with the clinical development of these therapies against AMR pathogens, are highlighted.
Overnutrition, Hyperinsulinemia and Ectopic Fat: It Is Time for A Paradigm Shift in the Management of Type 2 Diabetes
Authors: Janssen Joseph A. M. J. L.
Published: May 2024

The worldwide incidence of prediabetes/type 2 has continued to rise the last 40 years. In the same period, the mean daily energy intake has increased, and the quality of food has significantly changed. The chronic exposure of pancreatic β-cells to calorie excess (excessive energy intake) and food additives may increase pancreatic insulin secretion, decrease insulin pulses and/or reduce hepatic insulin clearance, thereby causing chronic hyperinsulinemia and peripheral insulin resistance. Chronic calorie excess and hyperinsulinemia may promote lipogenesis, inhibit lipolysis and increase lipid storage in adipocytes. In addition, calorie excess and hyperinsulinemia can induce insulin resistance and contribute to progressive and excessive ectopic fat accumulation in the liver and pancreas by the conversion of excess calories into fat. The personal fat threshold hypothesis proposes that in susceptible individuals, excessive ectopic fat accumulation may eventually lead to hepatic insulin receptor resistance, the loss of pancreatic insulin secretion, hyperglycemia and the development of frank type 2 diabetes. Thus, type 2 diabetes seems (partly) to be caused by hyperinsulinemia-induced excess ectopic fat accumulation in the liver and pancreas. Increasing evidence further shows that interventions (hypocaloric diet and/or bariatric surgery), which remove ectopic fat in the liver and pancreas by introducing a negative energy balance, can normalize insulin secretion and glucose tolerance and induce the sustained biochemical remission of type 2 diabetes. This pathophysiological insight may have major implications and may cause a paradigm shift in the management of type 2 diabetes: avoiding/reducing ectopic fat accumulation in the liver and pancreas may both be essential to prevent and cure type 2 diabetes.
Soluble Fluorinated Cardo Copolyimide as an Effective Additive to Photopolymerizable Compositions Based on Di(meth)acrylates: Application for Highly Thermostable Primary Protective Coating of Silica Optical Fiber
Authors: Sapozhnikov Dmitriy A. , Melnik Olga A. , Chuchalov Alexander V. , Kovylin Roman S. , Chesnokov Sergey A. , Khanin Dmitriy A. , Nikiforova Galina G. , Kosolapov Alexey F. , Semjonov Sergey L. , Vygodskii Yakov S.
Published: May 2024

The development of photocurable compositions is in high demand for the manufacture of functional materials for electronics, optics, medicine, energy, etc. The properties of the final photo-cured material are primarily determined by the initial mixture, which needs to be tuned for each application. In this study we propose to use simple systems based on di(meth)acrylate, polyimide and photoinitiator for the preparation of new photo-curable compositions. It was established that a fluorinated cardo copolyimide (FCPI) based on 2,2-bis-(3,4-dicarboxydiphenyl)hexafluoropropane dianhydride, 9,9-bis-(4-aminophenyl)fluorene and 2,2-bis-(4-aminophenyl)hexafluoropropane (1.00:0.75:0.25 mol) has excellent solubility in di(met)acrylates. This made it possible to prepare solutions of FCPI in such monomers, to study the effect of FCPI on the kinetics of their photopolymerization in situ and the properties of the resulting polymers. According to the obtained data, the solutions of FCPI (23 wt.%) in 1,4-butanediol diacrylate (BDDA) and FCPI (15 wt.%) in tetraethylene glycol diacrylate were tested for the formation of the primary protective coatings of the silica optical fibers. It was found that the new coating of poly(BDDA–FCPI23%) can withstand prolonged annealing at 200 °C (72 h), which is comparable or superior to the known most thermally stable photo-curable coatings. The proposed approach can be applied to obtain other functional materials.
Eco-Friendly Inorganic Binders: A Key Alternative for Reducing Harmful Emissions in Molding and Core-Making Technologies
Authors: Kmita Angelika , Dańko Rafał , Holtzer Mariusz , Dańko Józef , Drożyński Dariusz , Skrzyński Mateusz , Roczniak Agnieszka , Gruszka Daniel Robert , Jakubski Jarosław , Tapola Sara
Published: May 2024

Many years of foundry practice and much more accurate analytical methods have shown that sands with organic binders, in addition to their many technological advantages, pose risks associated with the emission of many compounds, including harmful ones (e.g., formaldehyde, phenol, benzene, polycyclic aromatic hydrocarbons, and sulfur), arising during the pouring of liquid casting alloys into molds, their cooling, and knock-out. The aim of this research is to demonstrate the potential benefits of adopting inorganic binders in European iron foundries. This will improve the environmental and working conditions by introducing cleaner and more ecological production methods, while also ranking the tested binders studied in terms of their harmful content. The article pays special attention to the analysis of seven innovative inorganic binders and one organic binder, acting as a reference for emissions of gases from the BTEX (benzene, toluene, ethylbenzene, and xylenes) and PAHs (polycyclic aromatic hydrocarbons) groups and other compounds such as phenol, formaldehyde, and isocyanates (MDI and TDI) generated during the mold pouring process with liquid metals. The knowledge gained will, for the first time, enrich the database needed to update the Reference Document on The Best Available Techniques for the Smitheries and Foundries Industry (SF BREF).
Green Extraction of Depsidones and Depsides from Hypogymnia physodes (L.) Nyl. Using Natural Deep Eutectic Solvents
Authors: Baczewska Izabela , Strzemski Maciej , Feldo Marcin , Hanaka Agnieszka , Dresler Sławomir
Published: May 2024

Various studies have shown that Hypogymnia physodes are a source of many biologically active compounds, including lichen acids. These lichen-specific compounds are characterized by antioxidant, antiproliferative, and antimicrobial properties, and they can be used in the cosmetic and pharmaceutical industries. The main aim of this study was to optimize the composition of natural deep eutectic solvents based on proline or betaine and lactic acid for the extraction of metabolites from H. physodes. The design of the experimental method and the response surface approach allowed the optimization of the extraction process of specific lichen metabolites. Based on preliminary research, a multivariate model of the experiment was developed. For optimization, the following parameters were employed in the experiment to confirm the model: a proline/lactic acid/water molar ratio of 1:2:2. Such a mixture allowed the efficient extraction of three depsidones (i.e., physodic acid, physodalic acid, 3-hydroyphysodic acid) and one depside (i.e., atranorin). The developed composition of the solvent mixtures ensured good efficiency when extracting the metabolites from the thallus of H. physodes with high antioxidant properties.
Mitochondrial RNA Helicases: Key Players in the Regulation of Plant Organellar RNA Splicing and Gene Expression
Authors: Mizrahi Ron , Ostersetzer-Biran Oren
Published: May 2024

Mitochondrial genomes of land plants are large and exhibit a complex mode of gene organization and expression, particularly at the post-transcriptional level. The primary organellar transcripts in plants undergo extensive maturation steps, including endo- and/or exo-nucleolytic cleavage, RNA-base modifications (mostly C-to-U deaminations) and both ‘cis’- and ‘trans’-splicing events. These essential processing steps rely on the activities of a large set of nuclear-encoded factors. RNA helicases serve as key players in RNA metabolism, participating in the regulation of transcription, mRNA processing and translation. They unwind RNA secondary structures and facilitate the formation of ribonucleoprotein complexes crucial for various stages of gene expression. Furthermore, RNA helicases are involved in RNA metabolism by modulating pre-mRNA maturation, transport and degradation processes. These enzymes are, therefore, pivotal in RNA quality-control mechanisms, ensuring the fidelity and efficiency of RNA processing and turnover in plant mitochondria. This review summarizes the significant roles played by helicases in regulating the highly dynamic processes of mitochondrial transcription, RNA processing and translation in plants. We further discuss recent advancements in understanding how dysregulation of mitochondrial RNA helicases affects the splicing of organellar genes, leading to respiratory dysfunctions, and consequently, altered growth, development and physiology of land plants.
Resonating with the World: Thinking Critically about Brain Criticality in Consciousness and Cognition
Authors: Leisman Gerry , Koch Paul
Published: May 2024

Aim: Biofields combine many physiological levels, both spatially and temporally. These biofields reflect naturally resonant forms of synaptic energy reflected in growing and spreading waves of brain activity. This study aims to theoretically understand better how resonant continuum waves may be reflective of consciousness, cognition, memory, and thought. Background: The metabolic processes that maintain animal cellular and physiological functions are enhanced by physiological coherence. Internal biological-system coordination and sensitivity to particular stimuli and signal frequencies are two aspects of coherent physiology. There exists significant support for the notion that exogenous biologically and non-biologically generated energy entrains human physiological systems. All living things have resonant frequencies that are either comparable or coherent; therefore, eventually, all species will have a shared resonance. An organism’s biofield activity and resonance are what support its life and allow it to react to stimuli. Methods: As the naturally resonant forms of synaptic energy grow and spread waves of brain activity, the temporal and spatial frequency of the waves are effectively regulated by a time delay (T) in inter-layer signals in a layered structure that mimics the structure of the mammalian cortex. From ubiquitous noise, two different types of waves can arise as a function of T. One is coherent, and as T rises, so does its resonant spatial frequency. Results: Continued growth eventually causes both the wavelength and the temporal frequency to abruptly increase. Two waves expand simultaneously and randomly interfere in an area of T values as a result. Conclusion: We suggest that because of this extraordinary dualism, which has its roots in the phase relationships of amplified waves, coherent waves are essential for memory retrieval, whereas random waves represent original cognition.
ACME: A Classification Model for Explaining the Risk of Preeclampsia Based on Bayesian Network Classifiers and a Non-Redundant Feature Selection Approach
Authors: Parrales-Bravo Franklin , Caicedo-Quiroz Rosangela , Rodríguez-Larraburu Elianne , Barzola-Monteses Julio
Published: May 2024

While preeclampsia is the leading cause of maternal death in Guayas province (Ecuador), its causes have not yet been studied in depth. The objective of this research is to build a Bayesian network classifier to diagnose cases of preeclampsia while facilitating the understanding of the causes that generate this disease. Data for the years 2017 through 2023 were gathered retrospectively from medical histories of patients treated at “IESS Los Ceibos” hospital in Guayaquil, Ecuador. Naïve Bayes (NB), The Chow–Liu Tree-Augmented Naïve Bayes (TANcl), and Semi Naïve Bayes (FSSJ) algorithms have been considered for building explainable classification models. A proposed Non-Redundant Feature Selection approach (NoReFS) is proposed to perform the feature selection task. The model trained with the TANcl and NoReFS was the best of them, with an accuracy close to 90%. According to the best model, patients whose age is above 35 years, have a severe vaginal infection, live in a rural area, use tobacco, have a family history of diabetes, and have had a personal history of hypertension are those with a high risk of developing preeclampsia.
High-Flow Nasal Cannula System in Respiratory Failure Associated with Interstitial Lung Diseases: A Systematic Review and Narrative Synthesis
Authors: Pagliaro Raffaella , Aronne Luigi , Fomez Ramona , Ferri Vincenzo , Montella Antonia , Sanduzzi Zamparelli Stefano , Bianco Andrea , Perrotta Fabio
Published: May 2024

Background: High-flow nasal cannula (HFNC) therapy has emerged as a promising treatment modality for interstitial lung disease (ILD)-related respiratory failure. This systematic review aims to evaluate the efficacy and safety of HFNC therapy in patients with ILDs. Methods: A comprehensive literature search was conducted using major electronic databases to identify relevant studies investigating the use of HFNC therapy in ILD patients with respiratory failure. Outcome measures of interest included improvements in oxygenation, dyspnea relief, respiratory rate control, hospital length of stay, and mortality. Results: Twelve studies were analyzed with an overall population of 715 patients included. Idiopathic Pulmonary Fibrosis (IPF) was the most prevalent type of ILD. Evaluated clinical settings were acute (7 studies), chronic (2 studies), and end-stage (3 studies) ILDs. The HFNC as a support for acute respiratory failure seems not inferior to non-invasive ventilation while offering better comfort and patient’s perception. Poor data are available about use in chronic/long-term or rehabilitative settings. In end of life/palliative care, an HFNC might improve quality of life. Despite the promising results, further research is warranted to establish optimal HFNC protocols, identify patient subgroups most likely to benefit, and explore long-term outcomes. Conclusions: Overall, the HFNC appears to be a valuable therapeutic option for managing respiratory failure in ILD patients, offering potential improvements in oxygenation and symptom relief.
Modified Implant Fixation Technique Is an Alternative for Patients with an Anterior Cruciate Ligament Tear in Limited Resource Settings: A Comparison Functional Outcome Study with Polyether Ether Ketone and Bioabsorbable Screws
Authors: Sakti Muhammad , Wawolumaja Arian Fardin Ignatius , Saleh Ruksal , Usman Muhammad Andry , Arifin Jainal , Johan Muhammad Phetrus
Published: May 2024

Background: Anterior cruciate ligament (ACL) injury is one of the most prevalent factors contributing to knee instability worldwide. This study aimed to evaluate modified metal fixation techniques for ACL reconstruction compared to factory-made implants, such as polyether ether ketone (PEEK) screws, bioabsorbable screws, and modified metal implants. Methods: A retrospective cohort analysis was conducted to assess the functional outcomes of ACL using various fixation methods. Patients who underwent arthroscopic ACL reconstruction at several healthcare facilities were included in the study. The functional outcomes were evaluated using the Lysholm Knee Scoring Scale and the International Knee Documentation Committee (IKDC) score questionnaire at 6- and 12 months post-surgery. Statistical analyses, including the Shapiro–Wilk test and analysis of variance, were performed to compare outcomes among the fixation groups. Results: Thirty-three patients who underwent ACL reconstruction surgery with varying distributions across the three fixation groups (modified metal implants, PEEK screws, and bioabsorbable screws) were included in the study. As measured by the Lysholm and IKDC scores at 6- and 12 months post-surgery, the PEEK group demonstrated the highest average scores. Nevertheless, these functional outcomes were not significantly different between the groups (p = 0.140, 0.770, 0.150, and 0.200). These findings align with those of meta-analyses comparing different fixation methods for ACL reconstruction. Conclusions: While acknowledging the small sample size as a limitation, this study suggests that modified metal implants represent viable options for ACL reconstruction. The selection of fixation methods should consider patient characteristics and preferences, emphasizing biomechanical stability and long-term outcomes. Further research is needed to validate these findings and explore their biomechanical properties and cost-effectiveness.
Comparative Analysis of Interfacial Adaptation and Depth Penetration of Recent HiFlow versus Regular Bioceramic Sealers in Conjunction with BC Gutta-Percha Points Using Two Different Obturation Techniques—A Preliminary Report of an Ex Vivo Study
Authors: Abu-Zeid Sawsan T. , Alamoudi Ruaa A.
Published: May 2024

This study aimed to assess the adaptability and penetration depth capacity of recent bioceramic systems, including regular EndoSequence (BC) versus HiFlow (BCH) sealers in the presence of BC points. A total of 54 single-rooted teeth were instrumented and obturated with either the cold or warm compaction technique (n = 9), using either BC, BCH, or AH Plus (AHP) combined with BC points. The adaptation, film thickness, and gaps/voids were evaluated by scanning electron microscopy. The sealer/dentin interface was evaluated by Raman spectroscopy, and depth penetration was evaluated by a confocal laser scanning microscope. According to the normality test, the data were statistically analyzed by ANOVA or Kruskal–Wallis and Mann–Whitney U tests at p < 0.05. BCH sealer showed the significantly thinnest film with the greatest flow (p > 0.001), with further improvement when subjected to the warm compaction technique. Moreover, it exhibited close adaptation with deep penetration into radicular dentin, forming a tag-like structure. The Raman spectra also indicated close contact with the dentin surface. The use of BC sealer with BC points exhibited homogenous, single-unit obturation, either with a cold or warm technique. Furthermore, the use of the warm compaction technique with BCH sealer achieved a gap-free interface associated with tag-like structures, which exhibit the monoblock phenomenon.
Digital Twin Modeling for Smart Injection Molding
Authors: Nasiri Sara , Khosravani Mohammad Reza , Reinicke Tamara , Ovtcharova Jivka
Published: May 2024

In traditional injection molding, each level of the process has its own monitoring and improvement initiatives. But in the upcoming industrial revolution, it is important to establish connections and communication among all stages, as changes in one stage might have an impact on others. To address this issue, digital twins (DTs) are introduced as virtual models that replicate the entire injection molding process. This paper focuses on the data and technology needed to build a DT model for injection molding. Each stage can have its own DT, which are integrated into a comprehensive model of the process. DTs enable the smart automation of production processes and data collection, reducing manual efforts in supervising and controlling production systems. However, implementing DTs is challenging and requires effort for conception and integration with the represented systems. To mitigate this, the current work presents a model for systematic knowledge-based engineering for the DTs of injection molding. This model includes fault detection systems, 3D printing, and system integration to automate development activities. Based on knowledge engineering, data analysis, and data mapping, the proposed DT model allows fault detection, prognostic maintenance, and predictive manufacturing.
Effectiveness of Several GRAS Salts against Fungal Rot of Fruit after Harvest and Assessment of the Phytotoxicity of Sodium Metabisufite in Treated Fruit
Authors: Allagui Mohamed Bechir , Ben Amara Mouna
Published: May 2024

This study evaluates the efficacy of the salts sodium metabisulfite (SMB), ammonium bicarbonate, sodium bicarbonate, and potassium dihydrogen orthophosphate first in vitro against the main postharvest fruit rot fungi, Alternaria alternata, Botrytis cinerea, Penicillium italicum, and Penicillium digitatum. Results showed that 0.2% SMB completely inhibited the mycelium growth of the fungal species. Ammonium bicarbonate and sodium bicarbonate were less effective at 0.2% in inhibiting mycelial growth, ranging from 57.6% to 77.6%. The least effective was potassium dihydrogen orthophosphate. Experiments were also performed in vivo on wounded apples inoculated with the most pathogenic fungus, B. cinerea, and treated with SMB at concentrations of 0.2, 0.5, 1, 2, and 3%, both preventively and curatively. Results based on the decay size showed that SMB, when used as a preventive treatment, had a reduced efficacy, even with the highest concentration. However, this salt proved to be very effective at 0.5% in curative treatment since the decay was completely blocked. Our results suggest that the appropriate concentration of SMB for post-harvest treatment is 0.5% as a curative treatment. On the other hand, the 1% dose induced the onset of phytotoxicity around the wound. To assess the extent of the phytotoxicity reaction, higher concentrations of 1–4% SMB were applied to wounded fruit. Apples and oranges were inoculated or not with B. cinerea and P. digitatum, respectively. Doses of 1–4% induced phytotoxicity in the form of a discolored ring surrounding the wound on the epidermis of the fruit; this phytotoxicity enlarged as the concentration of SMB increased. The phytotoxic features were similar on apples and oranges. The methodological procedure made it possible to carry out a quantitative assessment of SMB phytotoxicity. This method is proposed as an easy-to-use technique for quantitatively estimating the phytotoxicity of antifungal compounds on post-harvest fruit.
Constructive Journalistic Roles in Environments of Social Complexity and Political Crisis
Authors: Rojas-Calderón Alfredo
Published: May 2024

This exploratory and analytical research examines secondary sources to propose a résumé of professional roles for journalists to revitalize their roles within social and political coexistence. It aims to bridge the gap between theoretical concepts and practical applications, enhancing journalists’ impact on public discourse and informed decision-making. Empirical research will guide these roles’ implementation in real-world journalistic practices. Twelve explanatory and constructive journalistic roles are formulated, whose relevance and application are enhanced in societies undergoing crisis situations or serious difficulties and are at risk of rupture in coexistence. In conclusion, the role of journalists in the current circumstances of crises in democratic societies requires them to not only report on events but also provide context, analysis, and solutions to the complex issues faced by society. Journalistic functions such as contextualization, public interest promotion, dialogue, and motivation are considered fundamental beyond constructive journalism or solutions journalism.
Interactions and Trends of Interleukins, PAI-1, CRP, and TNF-α in Inflammatory Responses during the Perioperative Period of Joint Arthroplasty: Implications for Pain Management—A Narrative Review
Authors: Cocea Arabela-Codruta , Stoica Cristian Ioan
Published: May 2024

Inflammation during the perioperative period of joint arthroplasty is a critical aspect of patient outcomes, influencing both the pathophysiology of pain and the healing process. This narrative review comprehensively evaluates the roles of specific cytokines and inflammatory biomarkers in this context and their implications for pain management. Inflammatory responses are initiated and propagated by cytokines, which are pivotal in the development of both acute and chronic postoperative pain. Pro-inflammatory cytokines play essential roles in up-regulating the inflammatory response, which, if not adequately controlled, leads to sustained pain and impaired tissue healing. Anti-inflammatory cytokines work to dampen inflammatory responses and promote resolution. Our discussion extends to the genetic and molecular influences on cytokine production, which influence pain perception and recovery rates post-surgery. Furthermore, the role of PAI-1 in modulating inflammation through its impact on the fibrinolytic system highlights its potential as a therapeutic target. The perioperative modulation of these cytokines through various analgesic and anesthetic techniques, including the fascia iliac compartment block, demonstrates a significant reduction in pain and inflammatory markers, thus underscoring the importance of targeted therapeutic strategies. Our analysis suggests that a nuanced understanding of the interplay between pro-inflammatory and anti-inflammatory cytokines is required. Future research should focus on individualized pain management strategies.
Preferred Imaging for Target Volume Delineation for Radiotherapy of Recurrent Glioblastoma: A Literature Review of the Available Evidence
Authors: Cuccia Francesco , Jafari Fatemeh , D’Alessandro Salvatore , Carruba Giuseppe , Craparo Giuseppe , Tringali Giovanni , Blasi Livio , Ferrera Giuseppe
Published: May 2024

Background: Recurrence in glioblastoma lacks a standardized treatment, prompting an exploration of re-irradiation’s efficacy. Methods: A comprehensive systematic review from January 2005 to May 2023 assessed the role of MRI sequences in recurrent glioblastoma re-irradiation. The search criteria, employing MeSH terms, targeted English-language, peer-reviewed articles. The inclusion criteria comprised both retrospective and prospective studies, excluding certain types and populations for specificity. The PICO methodology guided data extraction, and the statistical analysis employed Chi-squared tests via MedCalc v22.009. Results: Out of the 355 identified studies, 81 met the criteria, involving 3280 patients across 65 retrospective and 16 prospective studies. The key findings indicate diverse treatment modalities, with linac-based photons predominating. The median age at re-irradiation was 54 years, and the median time interval between radiation courses was 15.5 months. Contrast-enhanced T1-weighted sequences were favored for target delineation, with PET-imaging used in fewer studies. Re-irradiation was generally well tolerated (median G3 adverse events: 3.5%). The clinical outcomes varied, with a median 1-year local control rate of 61% and a median overall survival of 11 months. No significant differences were noted in the G3 toxicity and clinical outcomes based on the MRI sequence preference or PET-based delineation. Conclusions: In the setting of recurrent glioblastoma, contrast-enhanced T1-weighted sequences were preferred for target delineation, allowing clinicians to deliver a safe and effective therapeutic option; amino acid PET imaging may represent a useful device to discriminate radionecrosis from recurrent disease. Future investigations, including the ongoing GLIAA, NOA-10, ARO 2013/1 trial, will aim to refine approaches and standardize methodologies for improved outcomes in recurrent glioblastoma re-irradiation.
Mechanical and Tribological Behavior of Nitrided AISI/SAE 4340 Steel Coated with NiP and AlCrN
Authors: Soares Marcos E. , He Qianxi , DePaiva Jose M. , de Freitas Bruna M. , Soares Paulo , Veldhuis Stephen C. , Amorim Fred L. , Torres Ricardo D.
Published: May 2024

In this study, novel surface engineering strategies to improve the wear performance of AISI 4340 were investigated. The strategies were as follows: (i) NiP deposition on a previously nitrided steel substrate, followed by NiP interdiffusion heat treatment at either 400 °C or 610 °C (referred to as duplex treatment); (ii) the deposition of AlCrN PVD coating on NiP layers on a previously nitrided steel substrate (referred to as triplex treatment). Prior to the deposition of AlCrN, the NiP was subjected to the interdiffusion heat treatment at either 400 °C or 610 °C. These strategies were compared with the performance of the AlCrN coating directly applied on nitrided steel. To characterize the microstructural features of each layer, X-ray diffraction (XRD) and scanning electron microscopy (SEM) coupled with energy-dispersive X-ray spectroscopy (EDS) analysis were conducted. We also carried out mechanical and tribological behavior assessments. The tribological tests were carried out using a ball-on-disc tribometer under a constant load of 20 N and a tangential speed of 25 cm/s; cemented carbide spheres with a diameter of 6 mm were the counterpart body. The friction coefficient was continuously monitored throughout the tests. The results reveal that the wear mechanism for the AlCrN coating is predominantly oxidative. The most wear-resistant surface architecture was the one comprising AlCrN over the NiP layer subjected to interdiffusion heat treatment at either 400 °C or 610 °C.
A Novel Load-Sharing System to Simulate the Creep of Strain-Hardening Cementitious Composites (SHCCs) in Practical Situations
Authors: Ratnayake Karuna Arachchige Shan Dilruksha , Leung Christopher Kin Ying
Published: May 2024

The ductility and exhibition of the multiple, fine, self-controlled cracking of strain-hardening cementitious composites (SHCCs) under tension has made them attractive for enhancing the durability of civil infrastructure. These fine cracks are key to preventing the ingress of water and harmful chemicals into the structure and thereby achieving steel reinforcement. However, several studies have suggested that the short-term fine cracks shown in the laboratory may end up exceeding the acceptable crack widths that are specified in design codes when SHCC members are subjected to sustained constant loads. In real structures, however, the load is also shared by the steel reinforcement in the member, so the SHCC within may not be under a constant load; therefore, the crack widening will not be as severe. This study focuses on the creep behaviour of SHCCs when they are applied as an external layer on reinforced concrete to enhance durability. A novel approach to simulate various stress–strain regimes in such systems is developed by using a fixture to share a sustained moment exclusively between a reinforcement member and SHCC. The developed load-sharing system allows stresses within the reinforcement and SHCC to be monitored against time during the imposed loading, while ensuring access to the SHCC layer for instrumentation and monitoring of strain/cracking. The time-dependent widening of cracks in the SHCC layer is found to be much less significant than that under constant loading, so resistance to water/chemical penetration can still be ensured in the long term. The obtained information on the variation in stress, strain, and crack opening with time will be useful for the development of a general model for the creep behaviour of SHCC members.
Research on Laser Cleaning Technology for Aircraft Skin Surface Paint Layer
Authors: Li Jinxuan , Yang Jianjun , Liu Jiaxuan , Chen Hui , Duan Yunfei , Pan Xinjian
Published: May 2024

In this study, a pulsed laser operating at a wavelength of 1064 nm and with a pulse width of 100 ns was utilized for the removal of paint from the surface of a 2024 aluminum alloy. The experimental investigation was conducted to analyze the influence of laser parameters on the efficacy of paint layer removal from the aircraft skin’s surface and the subsequent evolution in the microstructure of the laser-treated aluminum alloy substrate. The mechanism underlying laser cleaning was explored through simulation. The findings revealed that power density and scanning speed significantly affected the quality of cleaning. Notably, there were discernible damage thresholds and optimal cleaning parameters in repetitive frequency, with a power density of 178.25 MW/cm2, scanning speed of 500 mm/s, and repetitive frequency of 40 kHz identified as the primary optimal settings for achieving the desired cleaning effect. Thermal ablation and thermal vibration were identified as the principal mechanisms of cleaning. Moreover, laser processing induced surface dislocations and concentrated stress, accompanied by grain refinement, on the aluminum substrate.