bluuebunny/crossref_metadata_2025 huggingface dataset:
Monocytes and Macrophages in Kidney Disease and Homeostasis
Authors: Nachiappa Ganesh Rajesh , Garcia Gabriela , Truong Luan
Published: March 2024

The monocyte–macrophage lineage of inflammatory cells is characterized by significant morphologic and functional plasticity. Macrophages have broad M1 and M2 phenotype subgroups with distinctive functions and dual reno-toxic and reno-protective effects. Macrophages are a major contributor to injury in immune-complex-mediated, as well as pauci-immune, glomerulonephritis. Macrophages are also implicated in tubulointerstitial and vascular disease, though there have not been many human studies. Patrolling monocytes in the intravascular compartment have been reported in auto-immune injury in the renal parenchyma, manifesting as acute kidney injury. Insights into the pathogenetic roles of macrophages in renal disease suggest potentially novel therapeutic and prognostic biomarkers and targeted therapy. This review provides a concise overview of the macrophage-induced pathogenetic mechanism as a background for the latest findings about macrophages’ roles in different renal compartments and common renal diseases.
Revealing the Interaction Mechanism between Mycobacterium tuberculosis GyrB and Novobiocin, SPR719 through Binding Thermodynamics and Dissociation Kinetics Analysis
Authors: Qiu Xiaofei , Zhang Qianqian , Li Zhaoguo , Zhang Juan , Liu Huanxiang
Published: March 2024

With the rapid emergence of drug-resistant strains of Mycobacterium tuberculosis (Mtb), various levels of resistance against existing anti-tuberculosis (TB) drugs have developed. Consequently, the identification of new anti-TB targets and drugs is critically urgent. DNA gyrase subunit B (GyrB) has been identified as a potential anti-TB target, with novobiocin and SPR719 proposed as inhibitors targeting GyrB. Therefore, elucidating the molecular interactions between GyrB and its inhibitors is crucial for the discovery and design of efficient GyrB inhibitors for combating multidrug-resistant TB. In this study, we revealed the detailed binding mechanisms and dissociation processes of the representative inhibitors, novobiocin and SPR719, with GyrB using classical molecular dynamics (MD) simulations, tau-random acceleration molecular dynamics (τ-RAMD) simulations, and steered molecular dynamics (SMD) simulations. Our simulation results demonstrate that both electrostatic and van der Waals interactions contribute favorably to the inhibitors’ binding to GyrB, with Asn52, Asp79, Arg82, Lys108, Tyr114, and Arg141 being key residues for the inhibitors’ attachment to GyrB. The τ-RAMD simulations indicate that the inhibitors primarily dissociate from the ATP channel. The SMD simulation results reveal that both inhibitors follow a similar dissociation mechanism, requiring the overcoming of hydrophobic interactions and hydrogen bonding interactions formed with the ATP active site. The binding and dissociation mechanisms of GyrB with inhibitors novobiocin and SPR719 obtained in our work will provide new insights for the development of promising GyrB inhibitors.
Liquiritin Carbomer Gel Cold Paste Promotes Healing of Solar Dermatitis in Mice
Authors: Huang Yanfang , Li Sijia , Pan Jinghua , Song Congjing , Chen Weiqiang , Zhang Yun
Published: March 2024

Ultraviolet radiation (UVR) has various effects on human cells and tissues, which can lead to a variety of skin diseases and cause inconvenience to people’s lives. Among them, solar dermatitis is one of the important risk factors for malignant melanoma, so prevention and treatment of solar dermatitis is very necessary. Additionally, liquiritin (LQ) has anti-inflammatory effects. In this study, we aimed to evaluate the anti-inflammatory and pro-wound healing effects of liquiritin carbomer gel cold paste (LQ-CG-CP) in vitro and in vivo. The results of MTT experiments showed no cytotoxicity of LQ at concentrations of 40 μg/mL and below and cell damage at UVB irradiation doses above 60 mJ/cm2. Moreover, LQ can promote cell migration. ELISA results also showed that LQ inhibited the elevation of the inflammatory factors tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6) after UVB irradiation. In the mouse model of solar dermatitis, 2% LQ-CG-CP showed the best therapeutic efficacy for wound healing and relief of itching compared to MEIBAO moist burn moisturizer (MEBO). What is more, the results of skin histopathological examination show that LQ-CG-CP promotes re-epithelialization, shrinks wounds, and promotes collagen production, thus promoting wound healing. Simultaneously, LQ-CG-CP reduced TNF-α, IL-1β, and IL-6 expression. In addition, LQ-CG-CP was not observed to cause histopathological changes and blood biochemical abnormalities in mice. Overall, LQ-CG-CP has great potential for the treatment of solar dermatitis.
Immunomodulation through Nutrition Should Be a Key Trend in Type 2 Diabetes Treatment
Authors: Napiórkowska-Baran Katarzyna , Treichel Paweł , Czarnowska Marta , Drozd Magdalena , Koperska Kinga , Węglarz Agata , Schmidt Oskar , Darwish Samira , Szymczak Bartłomiej , Bartuzi Zbigniew
Published: March 2024

An organism’s ability to function properly depends not solely on its diet but also on the intake of nutrients and non-nutritive bioactive compounds that exert immunomodulatory effects. This principle applies both to healthy individuals and, in particular, to those with concomitant chronic conditions, such as type 2 diabetes. However, the current food industry and the widespread use of highly processed foods often lead to nutritional deficiencies. Numerous studies have confirmed the occurrence of immune system dysfunction in patients with type 2 diabetes. This article elucidates the impact of specific nutrients on the immune system function, which maintains homeostasis of the organism, with a particular emphasis on type 2 diabetes. The role of macronutrients, micronutrients, vitamins, and selected substances, such as omega-3 fatty acids, coenzyme Q10, and alpha-lipoic acid, was taken into consideration, which outlined the minimum range of tests that ought to be performed on patients in order to either directly or indirectly determine the severity of malnutrition in this group of patients.
Laminin Alpha 2 Enhances the Protective Effect of Exosomes on Human iPSC-Derived Cardiomyocytes in an In Vitro Ischemia-Reoxygenation Model
Authors: Mesquita Fernanda C. P. , King Madelyn , da Costa Lopez Patricia Luciana , Thevasagayampillai Shiyanth , Gunaratne Preethi H. , Hochman-Mendez Camila
Published: March 2024

Ischemic heart disease, a leading cause of death worldwide, manifests clinically as myocardial infarction. Contemporary therapies using mesenchymal stromal cells (MSCs) and their derivative (exosomes, EXOs) were developed to decrease the progression of cell damage during ischemic injury. Laminin alpha 2 (LAMA2) is an important extracellular matrix protein of the heart. Here, we generated MSC-derived exosomes cultivated under LAMA2 coating to enhance human-induced pluripotent stem cell (hiPSC)-cardiomyocyte recognition of LAMA2-EXOs, thus, increasing cell protection during ischemia reoxygenation. We mapped the mRNA content of LAMA2 and gelatin-EXOs and identified 798 genes that were differentially expressed, including genes associated with cardiac muscle development and extracellular matrix organization. Cells were treated with LAMA2-EXOs 2 h before a 4 h ischemia period (1% O2, 5% CO2, glucose-free media). LAMA2-EXOs had a two-fold protective effect compared to non-treatment on plasma membrane integrity and the apoptosis activation pathway; after a 1.5 h recovery period (20% O2, 5% CO2, cardiomyocyte-enriched media), cardiomyocytes treated with LAMA2-EXOs showed faster recovery than did the control group. Although EXOs had a protective effect on endothelial cells, there was no LAMA2-enhanced protection on these cells. This is the first report of LAMA2-EXOs used to treat cardiomyocytes that underwent ischemia-reoxygenation injury. Overall, we showed that membrane-specific EXOs may help improve cardiomyocyte survival in treating ischemic cardiovascular disease.
Targeting Interleukin-13 Receptor α2 and EphA2 in Aggressive Breast Cancer Subtypes with Special References to Chimeric Antigen Receptor T-Cell Therapy
Authors: Kashyap Dharambir , Salman Huda
Published: March 2024

Breast cancer (BCA) remains the leading cause of cancer-related mortality among women worldwide. This review delves into the therapeutic challenges of BCA, emphasizing the roles of interleukin-13 receptor α2 (IL-13Rα2) and erythropoietin-producing hepatocellular receptor A2 (EphA2) in tumor progression and resistance. Highlighting their overexpression in BCA, particularly in aggressive subtypes, such as Her-2-enriched and triple-negative breast cancer (TNBC), we discuss the potential of these receptors as targets for chimeric antigen receptor T-cell (CAR-T) therapies. We examine the structural and functional roles of IL-13Rα2 and EphA2, their pathological significance in BCA, and the promising therapeutic avenues their targeting presents. With an in-depth analysis of current immunotherapeutic strategies, including the limitations of existing treatments and the potential of dual antigen-targeting CAR T-cell therapies, this review aims to summarize potential future novel, more effective therapeutic interventions for BCA. Through a thorough examination of preclinical and clinical studies, it underlines the urgent need for targeted therapies in combating the high mortality rates associated with Her-2-enriched and TNBC subtypes and discusses the potential role of IL-13Rα2 and EphA2 as promising candidates for the development of CAR T-cell therapies.
The Dual Role of Neutrophil Extracellular Traps (NETs) in Sepsis and Ischemia-Reperfusion Injury: Comparative Analysis across Murine Models
Authors: Kiwit Antonia , Lu Yuqing , Lenz Moritz , Knopf Jasmin , Mohr Christoph , Ledermann Yannick , Klinke-Petrowsky Michaela , Pagerols Raluy Laia , Reinshagen Konrad , Herrmann Martin , Boettcher Michael , Elrod Julia
Published: March 2024

A better understanding of the function of neutrophil extracellular traps (NETs) may facilitate the development of interventions for sepsis. The study aims to investigate the formation and degradation of NETs in three murine sepsis models and to analyze the production of reactive oxygen species (ROS) during NET formation. Murine sepsis was induced by midgut volvulus (720° for 15 min), cecal ligation and puncture (CLP), or the application of lipopolysaccharide (LPS) (10 mg/kg body weight i.p.). NET formation and degradation was modulated using mice that were genetically deficient for peptidyl arginine deiminase-4 (PAD4-KO) or DNase1 and 1L3 (DNase1/1L3-DKO). After 48 h, mice were killed. Plasma levels of circulating free DNA (cfDNA) and neutrophil elastase (NE) were quantified to assess NET formation and degradation. Plasma deoxyribonuclease1 (DNase1) protein levels, as well as tissue malondialdehyde (MDA) activity and glutathione peroxidase (GPx) activity, were quantified. DNase1 and DNase1L3 in liver, intestine, spleen, and lung tissues were assessed. The applied sepsis models resulted in a simultaneous increase in NET formation and oxidative stress. NET formation and survival differed in the three models. In contrast to LPS and Volvulus, CLP-induced sepsis showed a decreased and increased 48 h survival in PAD4-KO and DNase1/1L3-DKO mice, when compared to WT mice, respectively. PAD4-KO mice showed decreased formation of NETs and ROS, while DNase1/1L3-DKO mice with impaired NET degradation accumulated ROS and chronicled the septic state. The findings indicate a dual role for NET formation and degradation in sepsis and ischemia-reperfusion (I/R) injury: NETs seem to exhibit a protective capacity in certain sepsis paradigms (CLP model), whereas, collectively, they seem to contribute adversely to scenarios where sepsis is combined with ischemia-reperfusion (volvulus).
CC Chemokine Family Members’ Modulation as a Novel Approach for Treating Central Nervous System and Peripheral Nervous System Injury—A Review of Clinical and Experimental Findings
Authors: Ciechanowska Agata , Mika Joanna
Published: March 2024

Despite significant progress in modern medicine and pharmacology, damage to the nervous system with various etiologies still poses a challenge to doctors and scientists. Injuries lead to neuroimmunological changes in the central nervous system (CNS), which may result in both secondary damage and the development of tactile and thermal hypersensitivity. In our review, based on the analysis of many experimental and clinical studies, we indicate that the mechanisms occurring both at the level of the brain after direct damage and at the level of the spinal cord after peripheral nerve damage have a common immunological basis. This suggests that there are opportunities for similar pharmacological therapeutic interventions in the damage of various etiologies. Experimental data indicate that after CNS/PNS damage, the levels of 16 among the 28 CC-family chemokines, i.e., CCL1, CCL2, CCL3, CCL4, CCL5, CCL6, CCL7, CCL8, CCL9, CCL11, CCL12, CCL17, CCL19, CCL20, CCL21, and CCL22, increase in the brain and/or spinal cord and have strong proinflammatory and/or pronociceptive effects. According to the available literature data, further investigation is still needed for understanding the role of the remaining chemokines, especially six of them which were found in humans but not in mice/rats, i.e., CCL13, CCL14, CCL15, CCL16, CCL18, and CCL23. Over the past several years, the results of studies in which available pharmacological tools were used indicated that blocking individual receptors, e.g., CCR1 (J113863 and BX513), CCR2 (RS504393, CCX872, INCB3344, and AZ889), CCR3 (SB328437), CCR4 (C021 and AZD-2098), and CCR5 (maraviroc, AZD-5672, and TAK-220), has beneficial effects after damage to both the CNS and PNS. Recently, experimental data have proved that blockades exerted by double antagonists CCR1/3 (UCB 35625) and CCR2/5 (cenicriviroc) have very good anti-inflammatory and antinociceptive effects. In addition, both single (J113863, RS504393, SB328437, C021, and maraviroc) and dual (cenicriviroc) chemokine receptor antagonists enhanced the analgesic effect of opioid drugs. This review will display the evidence that a multidirectional strategy based on the modulation of neuronal–glial–immune interactions can significantly improve the health of patients after CNS and PNS damage by changing the activity of chemokines belonging to the CC family. Moreover, in the case of pain, the combined administration of such antagonists with opioid drugs could reduce therapeutic doses and minimize the risk of complications.
Exploring Skin Wound Healing Models and the Impact of Natural Lipids on the Healing Process
Authors: Choudhary Vivek , Choudhary Mrunal , Bollag Wendy B.
Published: March 2024

Cutaneous wound healing is a complex biological process involving a series of well-coordinated events aimed at restoring skin integrity and function. Various experimental models have been developed to study the mechanisms underlying skin wound repair and to evaluate potential therapeutic interventions. This review explores the diverse array of skin wound healing models utilized in research, ranging from rodent excisional wounds to advanced tissue engineering constructs and microfluidic platforms. More importantly, the influence of lipids on the wound healing process is examined, emphasizing their role in enhancing barrier function restoration, modulating inflammation, promoting cell proliferation, and promoting remodeling. Lipids, such as phospholipids, sphingolipids, and ceramides, play crucial roles in membrane structure, cell signaling, and tissue repair. Understanding the interplay between lipids and the wound microenvironment provides valuable insights into the development of novel therapeutic strategies for promoting efficient wound healing and tissue regeneration. This review highlights the significance of investigating skin wound healing models and elucidating the intricate involvement of lipids in the healing process, offering potential avenues for improving clinical outcomes in wound management.
Unraveling the Complexities of Mast Cells in Health and Disease
Authors: Firinu Davide
Published: March 2024

As we draw the curtain on this Special Issue dedicated to the intricate roles of mast cells (MCs) in health and disease, we reflect on the insights garnered from the array of research articles featured within the published papers of the International Journal of Molecular Sciences (IJMS) [...]
A Multi-Gene Signature of Non-Muscle-Invasive Bladder Cancer Identifies Patients Who Respond to Immunotherapies Including Bacillus Calmette–Guérin and Immune Checkpoint Inhibitors
Authors: Baek Seung-Woo , Leem Sun-Hee
Published: March 2024

Approximately 75% of bladder cancer cases originate as non-muscle-invasive bladder cancer (NMIBC). Despite initial diagnosis, NMIBC commonly recurs, with up to 45% advancing to muscle-invasive bladder cancer (MIBC) and metastatic disease. Treatment for high-risk NMIBC typically includes procedures like transurethral resection and, depending on recurrence risk, intravesical chemotherapy or immunotherapy such as Bacillus Calmette–Guérin (BCG). However, persistent shortages of BCG necessitate alternative first-line treatments. We aim to use a multi-gene signature in high-risk NMIBC patients to determine whether patients may benefit from immune checkpoint inhibitors (ICIs) as an alternative to BCG and to evaluate their clinical utility. The multi-gene signature obtained from the three independent NMIBC cohorts was applied to stratify the UROMOL2016 cohort (n = 476) using consensus clustering. Each subtype was distinguished by biological pathway analysis. Validation analysis using a machine learning algorithm was performed in six independent cohorts including the BRS (n = 283) cohort treated with BCG and the IMvigor210 (n = 298) clinical trials treated with PD-L1 inhibitors. Based on consensus cluster analysis, NMIBC patients in the UROMOL2016 cohort were classified into three classes exhibiting distinguished characteristics, including DNA damage repair (DDR). Survival analysis showed that the NMIBC-DDR class had the highest rates of disease progression (progression-free survival, p = 0.002 by log-rank test) in the UROMOL cohort and benefited from BCG and ICIs (respectively, p = 0.02 and p = 0.03 by log-rank test). This study suggests that the multi-gene signature may have a role in identifying high-risk NMIBC patients and improving the responsiveness of ICIs. Additionally, we propose immunotherapy as a new first-line treatment for patients with high-risk NMIBC because of the shortage of BCG supply. It is important to help more patients prioritize cancer immunotherapy.
Anti-Inflammatory Effects of a Novel Acetonitrile–Water Extract of Lens Culinaris against LPS-Induced Damage in Caco-2 Cells
Authors: Maqoud Fatima , Orlando Antonella , Tricarico Domenico , Antonacci Marina , Di Turi Annamaria , Giannelli Gianluigi , Russo Francesco
Published: March 2024

Natural compounds like flavonoids preserve intestinal mucosal integrity through their antioxidant, anti-inflammatory, and antimicrobial properties. Additionally, some flavonoids show prebiotic abilities, promoting the growth and activity of beneficial gut bacteria. This study investigates the protective impact of Lens culinaris extract (LE), which is abundant in flavonoids, on intestinal mucosal integrity during LPS-induced inflammation. Using Caco-2 cells as a model for the intestinal barrier, the study found that LE did not affect cell viability but played a cytoprotective role in the presence of LPS. LE improved transepithelial electrical resistance (TEER) and tight junction (TJ) protein levels, which are crucial for barrier integrity. It also countered the upregulation of pro-inflammatory genes TRPA1 and TRPV1 induced by LPS and reduced pro-inflammatory markers like TNF-α, NF-κB, IL-1β, and IL-8. Moreover, LE reversed the LPS-induced upregulation of AQP8 and TLR-4 expression. These findings emphasize the potential of natural compounds like LE to regulate the intestinal barrier and reduce inflammation’s harmful effects on intestinal cells. More research is required to understand their mechanisms and explore therapeutic applications, especially for gastrointestinal inflammatory conditions.
Whisper40: A Multi-Person Chinese Whisper Speaker Recognition Dataset Containing Same-Text Neutral Speech
Authors: Yang Jingwen , Zhou Ruohua
Published: March 2024

Whisper speaker recognition (WSR) has received extensive attention from researchers in recent years, and it plays an important role in medical, judicial, and other fields. Among them, the establishment of a whisper dataset is very important for the study of WSR. However, the existing whisper dataset suffers from the problems of a small number of speakers, short speech duration, and lack of neutral speech with the same-text as the whispered speech in the same dataset. To address this issue, we present Whisper40, a multi-person Chinese WSR dataset containing same-text neutral speech spanning around 655.90 min sourced from volunteers. In addition, we use the current state-of-the-art speaker recognition model to build a WSR baseline system and combine the idea of transfer learning for pre-training the speaker recognition model using neutral speech datasets and transfer the empirical knowledge of specific network layers to the WSR system. The Whisper40 and CHAINs datasets are then used to fine-tune the model with transferred specific layers. The experimental results show that the Whisper40 dataset is practical, and the time delay neural network (TDNN) model performs well in both the same/cross-scene experiments. The equal error rate (EER) of Chinese WSR after transfer learning is reduced by 27.62% in comparison.
The Effect of Ge Doping on α-Ag2S’s Thermoelectric and Mechanical Properties
Authors: Hrickova Gabriela , Mihok Frantisek , Molcanova Zuzana , Ballokova Beata , Mamrilla Wanda , Dzunda Robert , Lukacs Peter , Pietrikova Alena , Saksl Karel
Published: March 2024

Thermoelectric materials are capable of generating electrical energy in response to a temperature gradient. Non-renewable energy resources are depleting, so the development of renewable energy sources that are environmentally sustainable is essential. One potential application of these materials as an alternative energy source is in wearable electronics. Thermoelectric materials are used in common electrical devices, as well as by the military, in healthcare, and in space. As a ductile N-type semiconducting material, silver sulfide is one of the most promising materials in terms of thermoelectric potential. The properties of Ag2S can be improved by choosing the appropriate dopants. This study investigates the methods by which the thermoelectric, mechanical, and hardness properties of Ag2S are improved via Ge doping. The addition of Ge increases the Seebeck coefficient to a maximum of −87 μV·K−1 from −1051 μV·K−1 to P-type, bringing it closer to transitioning. In order to work, a thermoelectric generator requires both N- and P-type materials. By applying homojunctions made from similar materials, internal stresses caused by the varying thermal expansion rates of different materials are reduced. In order to demonstrate Ge integration, scanning electron microscopy and X-ray diffraction were applied to the sample microstructure. In addition, supplementation was used to increase the ductility and malleability of materials to make them suitable for power generation in wearable electronics. These materials showed significant power factor values according to room-temperature measurements. This proves that materials capable of generating usable voltage lie in the recommended ambient temperature range for the user’s body, thus rendering them potential candidates for wearable electronics.
In Drosophila Hemolymph, Serine Proteases Are the Major Gelatinases and Caseinases
Authors: Gatti Jean-Luc , Lemauf Séverine , Belghazi Maya , Arthaud Laury , Poirié Marylène
Published: March 2024

After separation on gel zymography, Drosophila melanogaster hemolymph displays gelatinase and caseinase bands of varying sizes, ranging from over 140 to 25 kDa. Qualitative and quantitative variations in these bands were observed during larval development and between different D. melanogaster strains and Drosophila species. The activities of these Drosophila hemolymph gelatinase and caseinase were strongly inhibited by serine protease inhibitors, but not by EDTA. Mass spectrometry identified over 60 serine proteases (SPs) in gel bands corresponding to the major D. melanogaster gelatinases and caseinases, but no matrix metalloproteinases (MMPs) were found. The most abundant proteases were tequila and members of the Jonah and trypsin families. However, the gelatinase bands did not show any change in the tequila null mutant. Additionally, no clear changes could be observed in D. melanogaster gel bands 24 h after injection of bacterial lipopolysaccharides (LPS) or after oviposition by Leptopilina boulardi endoparasitoid wasps. It can be concluded that the primary gelatinases and caseinases in Drosophila larval hemolymph are serine proteases (SPs) rather than matrix metalloproteinases (MMPs). Furthermore, the gelatinase pattern remains relatively stable even after short-term exposure to pathogenic challenges.
Characterization of Pig Vertebrae under Axial Compression Integrating Radiomic Techniques and Finite Element Analysis
Authors: Hernández-Salazar Cristian A. , Chamorro Camilo E. , González-Estrada Octavio A.
Published: March 2024

The study of pig bones, due to their similarity with human tissues, has facilitated the development of technological tools that help in the diagnosis of diseases and injuries affecting the skeletal system. Radiomic techniques involving medical image segmentation, along with finite element analysis, enable the detailed study of bone damage, loss of density, and mechanical functionality, which is a significant advancement in personalized medicine. This study involves conducting experimental tests on L3–L6 pig vertebrae under axial loading conditions. The mechanical properties of these vertebrae are analyzed, and the maximum loads they can sustain within the elastic range are determined. Additionally, three-dimensional models are generated by segmenting computerized axial tomography (CAT) scans of the vertebrae. Digital shadows of the vertebrae are constructed by assigning an anisotropic material model to the segmented geometries. Then, finite element analysis is performed to evaluate the elastic characteristics, stress, and displacement. The findings from the experimental data are then compared to the numerical model, revealing a strong correlation with differences of less than 0.8% in elastic modulus and 1.53% in displacement. The proposed methodology offers valuable support in achieving more accurate medical outcomes, employing models that serve as a diagnostic reference. Moreover, accurate bone modeling using finite element analysis provides valuable information to understand how implants interact with the surrounding bone tissue. This information is useful in guiding the design and optimization of implants, enabling the creation of safer, more durable, and biocompatible medical devices that promote optimal osseointegration and healing in the patient.
Cutting-Edge Techniques and Drugs for the Treatment of Pulmonary Embolism: Current Knowledge and Future Perspectives
Authors: Falsetti Lorenzo , Guerrieri Emanuele , Zaccone Vincenzo , Viticchi Giovanna , Santini Silvia , Giovenali Laura , Lagonigro Graziana , Carletti Stella , Gialluca Palma Linda Elena , Tarquinio Nicola , Moroncini Gianluca
Published: March 2024

Pulmonary embolism (PE) is a potentially life-threatening condition requiring prompt diagnosis and treatment. Recent advances have led to the development of newer techniques and drugs aimed at improving PE management, reducing its associated morbidity and mortality and the complications related to anticoagulation. This review provides an overview of the current knowledge and future perspectives on PE treatment. Anticoagulation represents the first-line treatment of hemodynamically stable PE, direct oral anticoagulants being a safe and effective alternative to traditional anticoagulation: these drugs have a rapid onset of action, predictable pharmacokinetics, and low bleeding risk. Systemic fibrinolysis is suggested in patients with cardiac arrest, refractory hypotension, or shock due to PE. With this narrative review, we aim to assess the state of the art of newer techniques and drugs that could radically improve PE management in the near future: (i) mechanical thrombectomy and pulmonary embolectomy are promising techniques reserved to patients with massive PE and contraindications or failure to systemic thrombolysis; (ii) catheter-directed thrombolysis is a minimally invasive approach that can be suggested for the treatment of massive or submassive PE, but the lack of large, randomized controlled trials represents a limitation to widespread use; (iii) novel pharmacological approaches, by agents inhibiting thrombin-activatable fibrinolysis inhibitor, factor Xia, and the complement cascade, are currently under investigation to improve PE-related outcomes in specific settings.
Prognostic Value of Postneoadjuvant Chemotherapy Neutrophil-to-Lymphocyte Ratio in Patients undergoing Radical Cystectomy
Authors: Kaczmarek Krystian , Małkiewicz Bartosz , Gurwin Adam , Krawczyk Wiktor Mateusz , Skonieczna-Żydecka Karolina , Lemiński Artur
Published: March 2024

Background: Neutrophil-to-lymphocyte ratio (NLR), a widely assessed biomarker in most common diseases, is typically evaluated before treatment initiation. However, data on NLR in the post-treatment setting is limited. Therefore, we assessed the NLR calculated after neoadjuvant chemotherapy (NAC) initiation in patients with bladder cancer (BC). We hypothesised that changes in blood cells after NAC could be a marker of tumour response and long-term survival. Materials and Methods: Our study included 214 patients who underwent NAC followed by radical cystectomy (RC) in two urological departments, wherein post-NAC NLR was used to categorize patients into the low (NLR ≤ 1.75) and high (NLR > 1.75) groups. Results: Logistic regression analysis indicated that a post-NAC NLR ≥ 1.75 is a good biomarker for pathologic response (odds ratio (OR), 0.045; p <0.001), emphasizing its ability to predict patient survival. The HRs for overall survival and cancer-specific survival were 2.387 (p = 0.048) and 2.342 (p < 0.001), respectively. Conclusions: We believe that post-NAC NLR can be used for patient stratification after NAC. Consequently, the post-NAC NLR may serve as a guide for the decision-making process regarding RC versus bladder-preserving strategies.
Correlation of Inflammatory Parameters with the Development of Cerebral Vasospasm, Takotsubo Cardiomyopathy, and Functional Outcome after Spontaneous Subarachnoid Hemorrhage
Authors: Szántó Dorottya , Luterán Péter , Kóti Nikolett , Siró Péter , Simon Éva , Jakab Zsuzsa , Gál Judit , Kappelmayer János , Fülesdi Béla , Molnár Csilla
Published: March 2024

Background: The present work aimed to determine whether a relationship exists between inflammatory parameters and the development of vasospasm (VS) and Takotsubo cardiomyopathy (TTC), as well as clinical outcome, in patients suffering from spontaneous subarachnoid hemorrhage (SAH). Methods: In this study, the authors processed the prospectively collected laboratory and clinical data of spontaneous SAH patients admitted to the neurointensive care unit between March 2015 and October 2023. The highest values of neutrophils (NEUpeak), monocytes (MONOpeak), neutrophil-to-lymphocyte ratio (NLRpeak), and CRP (CRPpeak) during the initial 7 days were correlated with the occurrence of VS and TTC, and with the outcome measures at day 30 after onset. Results: Data were collected from 175 SAH patients. Based on ROC analysis, for the development of VS, MONOpeak was the most accurate indicator (AUC: 0.619, optimal cut-off: 1.45 G/L). TTC with severe left ventricular dysfunction (ejection fraction < 40%) was indicated most sensitively by NEUpeak (ROC: 0.763, optimal cut-off: 12.34 G/L). Both for GOS and Barthel Index at day 30, CRPpeak was the best predictor for the outcome (GOS: ROC: 0.846, optimal cut-off: 78.33 mg/L and Barthel Index: ROC: 0.819, optimal cut-off: 78.33 mg/L). Conclusions: Laboratory parameters referring to inflammation during the initial 7 days after SAH correlate with the development of VS and TTC, and thus may predict functional outcome.
The Net Clinical Outcome of Dual-Pathway Inhibition in Clinical Practice: The “Xarelto plus Acetylsalicylic Acid: Treatment Patterns and Outcomes in Patients with Atherosclerosis” Registry
Authors: Breitenstein Alexander , Gay Alain , Vogtländer Kai , Fox Keith A. A. , Steffel Jan
Published: March 2024

Background: In the COMPASS trial, the combination of acetylsalicylic acid (ASA) plus 2.5 mg rivaroxaban twice daily (dual-pathway inhibition, DPI) has been shown to be superior to ASA monotherapy for the reduction in ischemic major adverse cardiovascular events (MACEs, i.e., cardiovascular death, stroke, or myocardial infarction). Methods: The international XATOA registry (Xarelto plus Acetylsalicylic acid: Treatment patterns and Outcomes in patients with Atherosclerosis) is a prospective post-approval registry that investigates the cardiovascular outcomes of patients taking ASA plus 2.5 mg rivaroxaban. The aim of this pre-specified analysis was to determine the net clinical outcome (NCO), i.e., a combination of MACEs and bleeding events, of DPI in patients from daily clinical practice. Results: Among the 5615 patients, the presence of multiple risk factors resulted in an increase in the total risk of experiencing an NCO event, e.g., from 1.27% (one risk factor) to 2.18% (two risk factors) and 4.07% (three or more risk factors), respectively, with ischemic MACE representing the primary driver of bleeding complications. Conclusions: In the real-world XATOA registry, the annual rate of NCO events was low and numerically similar to those seen in the treatment group in the randomized COMPASS trial.
Evaluation of Neuromuscular Diseases and Complaints by Quantitative Muscle MRI
Authors: Schlaffke Lara , Rehmann Robert , Güttsches Anne-Katrin , Vorgerd Matthias , Meyer-Frießem Christine H. , Dinse Hubert R. , Enax-Krumova Elena , Froeling Martijn , Forsting Johannes
Published: March 2024

Background: Quantitative muscle MRI (qMRI) is a promising tool for evaluating and monitoring neuromuscular disorders (NMD). However, the application of different imaging protocols and processing pipelines restricts comparison between patient cohorts and disorders. In this qMRI study, we aim to compare dystrophic (limb-girdle muscular dystrophy), inflammatory (inclusion body myositis), and metabolic myopathy (Pompe disease) as well as patients with post-COVID-19 conditions suffering from myalgia to healthy controls. Methods: Ten subjects of each group underwent a 3T lower extremity muscle MRI, including a multi-echo, gradient-echo, Dixon-based sequence, a multi-echo, spin-echo (MESE) T2 mapping sequence, and a spin-echo EPI diffusion-weighted sequence. Furthermore, the following clinical assessments were performed: Quick Motor Function Measure, patient questionnaires for daily life activities, and 6-min walking distance. Results: Different involvement patterns of conspicuous qMRI parameters for different NMDs were observed. qMRI metrics correlated significantly with clinical assessments. Conclusions: qMRI metrics are suitable for evaluating patients with NMD since they show differences in muscular involvement in different NMDs and correlate with clinical assessments. Still, standardisation of acquisition and processing is needed for broad clinical use.
Adherence to the CLOSE Protocol and Low Baseline Generator Impedance Are Independent Predictors of Durable Pulmonary Vein Isolation
Authors: Boga Márton , Orbán Gábor , Perge Péter , Salló Zoltán , Tanai Edit , Ferencz Arnold Béla , Tóth Patrik , Komlósi Ferenc , Osztheimer István , Nagy Klaudia Vivien , Merkely Béla , Gellér László , Szegedi Nándor
Published: March 2024

Background: Atrial fibrillation (AF) recurrence after pulmonary vein isolation (PVI) is predominantly attributed to pulmonary vein reconnection (PVR). Predictors of AF recurrence have been widely studied; however, data are scarce on procedural parameters that predict chronic PVR. We aimed to study PVR rates and predictors of PVR. Methods: We retrospectively included 100 patients who underwent repeated ablation due to AF recurrence after initial PVI with the CARTO system. PVR was determined during the repeated procedure by electrophysiological evaluation, and initial procedural characteristics predicting PVR were studied, including adherence to the CLOSE protocol, use of high power, first-pass isolation (FPI), and baseline generator impedance (BGI). Results: Thirty-eight patients underwent initial CLOSE-guided PVI, and sixty-two underwent initial non-CLOSE PVI. A repeat procedure was performed 23 ± 16 months after the initial procedure. In total, PVR was found in 192 of 373 PVs (51.5%), and all PVs were isolated in 17/100 (17%) patients. Factors associated with all PVs being isolated were adherence to the CLOSE protocol, a higher power setting, the presence of bilateral FPI, and lower BGI (88% vs. 28%, p < 0.0001; 37.5 W vs. 30 W, p = 0.0276; 88.2% vs. 40.4%, p = 0.0007; and 127.6 Ω vs. 136.6 Ω, p = 0.0027, respectively). In initial procedures with adherence to the CLOSE protocol, the FPI rate was significantly higher (73.7% vs. 25%, p < 0.0001), while there were no significant differences in terms of procedure time and left atrial dwell time (81 vs. 85 min, p = 0.83; and 60 vs. 58 min, p = 0.08, respectively). BGI ≥ 130 Ω (AUC = 0.7403, sensitivity: 77.1%, specificity: 68.8%, p = 0.0032) was associated with a significantly higher probability of PVR (OR = 6.757; p < 0.0001). In multivariable analysis, independent predictors for PVR were non-adherence to the CLOSE protocol and BGI ≥ 130 Ω. Conclusions: Our findings indicate that adherence to the CLOSE protocol and baseline generator impedance < 130 Ω during AF ablation are independent predictors of PVI durability.
Augmentation Rhinoplasty and Centrofacial Lipofilling: Our Experience (ARCL)
Authors: Pozzi Mirco , Susini Pietro , di Seclì Davide , Schettino Michela , Grimaldi Luca , Cuomo Roberto , Roxo Carlos Weck
Published: March 2024

Introduction: Augmentation rhinoplasty traditionally represents a serious challenge for plastic surgeons. The association with centrofacial lipofilling is a great approach to achieve harmonious, aesthetic results. The aim of this article is to describe our personal association between Augmentation Rhinoplasty and Centrofacial Lipofilling (ARCL) in non-Caucasian patients. Materials and Methods: In this study, we retrospectively reviewed patients treated with ARCL at our institution between January 2019 and December 2023. We described our personal approach and technique. At a minimum follow-up time of one year, post-operative pictures were taken, and patients were reassessed, evaluating aspects such as global symmetry, shape and contour of the nose, and facial harmony and rejuvenation; finally, patients’ satisfaction was investigated according to the ROE questionnaire and the modified S-GAIS. Results: A total of 307 patients were included in the study. They reported a significant satisfactory aesthetic result in nasal image and facial harmony, as the mean postoperative ROE and S-GAIS score show. None of the grafts extruded or collapsed. Wounds healed without reported major infection. Conclusions: This study has demonstrated that ARCL is a safe approach that contributes to improve functional and aesthetic outcomes, has a high patient satisfaction rate, and limited post-operative complications.
Stroke-Induced Secondary Neurodegeneration of the Corticospinal Tract—Time Course and Mechanisms Underlying Signal Changes in Conventional and Advanced Magnetic Resonance Imaging
Authors: Zedde Marialuisa , Grisendi Ilaria , Assenza Federica , Napoli Manuela , Moratti Claudio , Di Cecco Giovanna , D’Aniello Serena , Valzania Franco , Pascarella Rosario
Published: March 2024

Secondary neurodegeneration refers to the final result of several simultaneous and sequential mechanisms leading to the loss of substance and function in brain regions connected to the site of a primary injury. Stroke is one of the most frequent primary injuries. Among the subtypes of post-stroke secondary neurodegeneration, axonal degeneration of the corticospinal tract, also known as Wallerian degeneration, is the most known, and it directly impacts motor functions, which is crucial for the motor outcome. The timing of its appearance in imaging studies is usually considered late (over 4 weeks), but some diffusion-based magnetic resonance imaging (MRI) techniques, as diffusion tensor imaging (DTI), might show alterations as early as within 7 days from the stroke. The different sequential pathological stages of secondary neurodegeneration provide an interpretation of the signal changes seen by MRI in accordance with the underlying mechanisms of axonal necrosis and repair. Depending on the employed MRI technique and on the timing of imaging, different rates and thresholds of Wallerian degeneration have been provided in the literature. In fact, three main pathological stages of Wallerian degeneration are recognizable—acute, subacute and chronic—and MRI might show different changes: respectively, hyperintensity on T2-weighted sequences with corresponding diffusion restriction (14–20 days after the injury), followed by transient hypointensity of the tract on T2-weighted sequences, and by hyperintensity and atrophy of the tract on T2-weighted sequences. This is the main reason why this review is focused on MRI signal changes underlying Wallerian degeneration. The identification of secondary neurodegeneration, and in particular Wallerian degeneration, has been proposed as a prognostic indicator for motor outcome after stroke. In this review, the main mechanisms and neuroimaging features of Wallerian degeneration in adults are addressed, focusing on the time and mechanisms of tissue damage underlying the signal changes in MRI.
Magnetoencephalography Atlas Viewer for Dipole Localization and Viewing
Authors: Fonseca N.C.d. , Bowerman Jason , Askari Pegah , Proskovec Amy L. , Feltrin Fabricio Stewan , Veltkamp Daniel , Early Heather , Wagner Ben C. , Davenport Elizabeth M. , Maldjian Joseph A.
Published: March 2024

Magnetoencephalography (MEG) is a noninvasive neuroimaging technique widely recognized for epilepsy and tumor mapping. MEG clinical reporting requires a multidisciplinary team, including expert input regarding each dipole’s anatomic localization. Here, we introduce a novel tool, the “Magnetoencephalography Atlas Viewer” (MAV), which streamlines this anatomical analysis. The MAV normalizes the patient’s Magnetic Resonance Imaging (MRI) to the Montreal Neurological Institute (MNI) space, reverse-normalizes MNI atlases to the native MRI, identifies MEG dipole files, and matches dipoles’ coordinates to their spatial location in atlas files. It offers a user-friendly and interactive graphical user interface (GUI) for displaying individual dipoles, groups, coordinates, anatomical labels, and a tri-planar MRI view of the patient with dipole overlays. It evaluated over 273 dipoles obtained in clinical epilepsy subjects. Consensus-based ground truth was established by three neuroradiologists, with a minimum agreement threshold of two. The concordance between the ground truth and MAV labeling ranged from 79% to 84%, depending on the normalization method. Higher concordance rates were observed in subjects with minimal or no structural abnormalities on the MRI, ranging from 80% to 90%. The MAV provides a straightforward MEG dipole anatomic localization method, allowing a nonspecialist to prepopulate a report, thereby facilitating and reducing the time of clinical reporting.
Applied Artificial Intelligence in Healthcare: A Review of Computer Vision Technology Application in Hospital Settings
Authors: Lindroth Heidi , Nalaie Keivan , Raghu Roshini , Ayala Ivan N. , Busch Charles , Bhattacharyya Anirban , Moreno Franco Pablo , Diedrich Daniel A. , Pickering Brian W. , Herasevich Vitaly
Published: March 2024

Computer vision (CV), a type of artificial intelligence (AI) that uses digital videos or a sequence of images to recognize content, has been used extensively across industries in recent years. However, in the healthcare industry, its applications are limited by factors like privacy, safety, and ethical concerns. Despite this, CV has the potential to improve patient monitoring, and system efficiencies, while reducing workload. In contrast to previous reviews, we focus on the end-user applications of CV. First, we briefly review and categorize CV applications in other industries (job enhancement, surveillance and monitoring, automation, and augmented reality). We then review the developments of CV in the hospital setting, outpatient, and community settings. The recent advances in monitoring delirium, pain and sedation, patient deterioration, mechanical ventilation, mobility, patient safety, surgical applications, quantification of workload in the hospital, and monitoring for patient events outside the hospital are highlighted. To identify opportunities for future applications, we also completed journey mapping at different system levels. Lastly, we discuss the privacy, safety, and ethical considerations associated with CV and outline processes in algorithm development and testing that limit CV expansion in healthcare. This comprehensive review highlights CV applications and ideas for its expanded use in healthcare.
Synthetic-to-Real Composite Semantic Segmentation in Additive Manufacturing
Authors: Petsiuk Aliaksei , Singh Harnoor , Dadhwal Himanshu , Pearce Joshua M.
Published: March 2024

The application of computer vision and machine learning methods for semantic segmentation of the structural elements of 3D-printed products in the field of additive manufacturing (AM) can improve real-time failure analysis systems and potentially reduce the number of defects by providing additional tools for in situ corrections. This work demonstrates the possibilities of using physics-based rendering for labeled image dataset generation, as well as image-to-image style transfer capabilities to improve the accuracy of real image segmentation for AM systems. Multi-class semantic segmentation experiments were carried out based on the U-Net model and the cycle generative adversarial network. The test results demonstrated the capacity of this method to detect such structural elements of 3D-printed parts as a top (last printed) layer, infill, shell, and support. A basis for further segmentation system enhancement by utilizing image-to-image style transfer and domain adaptation technologies was also considered. The results indicate that using style transfer as a precursor to domain adaptation can improve real 3D printing image segmentation in situations where a model trained on synthetic data is the only tool available. The mean intersection over union (mIoU) scores for synthetic test datasets included 94.90% for the entire 3D-printed part, 73.33% for the top layer, 78.93% for the infill, 55.31% for the shell, and 69.45% for supports.