bluuebunny/crossref_metadata_2025 huggingface dataset:
Enhancing Targeted Therapy in Breast Cancer by Ultrasound-Responsive Nanocarriers
Authors: Edwards Isaiah A. , De Carlo Flavia , Sitta Juliana , Varner William , Howard Candace M. , Claudio Pier Paolo
Published: March 2023

Currently, the response to cancer treatments is highly variable, and severe side effects and toxicity are experienced by patients receiving high doses of chemotherapy, such as those diagnosed with triple-negative breast cancer. The main goal of researchers and clinicians is to develop new effective treatments that will be able to specifically target and kill tumor cells by employing the minimum doses of drugs exerting a therapeutic effect. Despite the development of new formulations that overall can increase the drugs’ pharmacokinetics, and that are specifically designed to bind overexpressed molecules on cancer cells and achieve active targeting of the tumor, the desired clinical outcome has not been reached yet. In this review, we will discuss the current classification and standard of care for breast cancer, the application of nanomedicine, and ultrasound-responsive biocompatible carriers (micro/nanobubbles, liposomes, micelles, polymeric nanoparticles, and nanodroplets/nanoemulsions) employed in preclinical studies to target and enhance the delivery of drugs and genes to breast cancer.
IL-1 Mediates Chronic Stress-Induced Hyperalgesia Accompanied by Microglia and Astroglia Morphological Changes in Pain-Related Brain Regions in Mice
Authors: Fülöp Barbara , Hunyady Ágnes , Bencze Noémi , Kormos Viktória , Szentes Nikolett , Dénes Ádám , Lénárt Nikolett , Borbély Éva , Helyes Zsuzsanna
Published: March 2023

Chronic stress causes several pain conditions including fibromyalgia. Its pathophysiological mechanisms are unknown, and the therapy is unresolved. Since the involvement of interleukin-1 (IL-1) has been described in stress and inflammatory pain but no data are available regarding stress-induced pain, we studied its role in a chronic restraint stress (CRS) mouse model. Female and male C57Bl/6J wild-type (WT) and IL-1αβ-deficient (knock-out: IL-1 KO) mice were exposed to 6 h of immobilization/day for 4 weeks. Mechanonociception, cold tolerance, behavioral alterations, relative thymus/adrenal gland weights, microglia ionized calcium-binding adaptor molecule 1 (IBA1) and astrocyte glial fibrillary acidic protein (GFAP) integrated density, number and morphological transformation in pain-related brain regions were determined. CRS induced 15–20% mechanical hyperalgesia after 2 weeks in WT mice in both sexes, which was significantly reduced in female but not in male IL-1 KOs. Increased IBA1+ integrated density in the central nucleus of amygdala, primary somatosensory cortex hind limb representation part, hippocampus cornu ammonis area 3 (CA3) and periaqueductal gray matter (PAG) was present, accompanied by a cell number increase in IBA1+ microglia in stressed female WTs but not in IL-1 KOs. CRS induced morphological changes of GFAP+ astrocytes in WT but not in KO mice. Stress evoked cold hypersensitivity in the stressed animals. Anxiety and depression-like behaviors, thymus and adrenal gland weight changes were detectable in all groups after 2 but not 4 weeks of CRS due to adaptation. Thus, IL-1 mediates chronic stress-induced hyperalgesia in female mice, without other major behavioral alterations, suggesting the analgesic potentials of IL-1 in blocking drugs in stress-related pain syndromes.
Comparison of the Effect of Different Conditioning Media on the Angiogenic Potential of Hypoxia Preconditioned Blood-Derived Secretomes: Towards Engineering Next-Generation Autologous Growth Factor Cocktails
Authors: Moog Philipp , Hughes Jessica , Jiang Jun , Röper Lynn , Dornseifer Ulf , Schilling Arndt F. , Machens Hans-Günther , Hadjipanayi Ektoras
Published: March 2023

Hypoxia Preconditioned Plasma (HPP) and Serum (HPS) are regenerative blood-derived growth factor compositions that have been extensively examined for their angiogenic and lymphangiogenic activity towards wound healing and tissue repair. Optimization of these secretomes’ growth factor profile, through adjustments of the conditioning parameters, is a key step towards clinical application. In this study, the autologous liquid components (plasma/serum) of HPP and HPS were replaced with various conditioning media (NaCl, PBS, Glucose 5%, AIM V medium) and were analyzed in terms of key pro- (VEGF-A, EGF) and anti-angiogenic (TSP-1, PF-4) protein factors, as well as their ability to promote microvessel formation in vitro. We found that media substitution resulted in changes in the concentration of the aforementioned growth factors, and also influenced their ability to induce angiogenesis. While NaCl and PBS led to a lower concentration of all growth factors examined, and consequently an inferior tube formation response, replacement with Glucose 5% resulted in increased growth factor concentrations in anticoagulated blood-derived secretomes, likely due to stimulation of platelet factor release. Medium substitution with Glucose 5% and specialized peripheral blood cell-culture AIM V medium generated comparable tube formation to HPP and HPS controls. Altogether, our data suggest that medium replacement of plasma and serum may significantly influence the growth factor profile of hypoxia-preconditioned blood-derived secretomes and, therefore, their potential application as tools for promoting therapeutic angiogenesis.
Deregulation of Astroglial TASK-1 K+ Channel Decreases the Responsiveness to Perampanel-Induced AMPA Receptor Inhibition in Chronic Epilepsy Rats
Authors: Lee Duk-Shin , Kim Tae-Hyun , Park Hana , Kang Tae-Cheon
Published: March 2023

Tandem of P domains in a weak inwardly rectifying K+ channel (TWIK)-related acid sensitive K+-1 channel (TASK-1) is activated under extracellular alkaline conditions (pH 7.2–8.2), which are upregulated in astrocytes (particularly in the CA1 region) of the hippocampi of patients with temporal lobe epilepsy and chronic epilepsy rats. Perampanel (PER) is a non-competitive α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor (AMPAR) antagonist used for the treatment of focal seizures and primary generalized tonic–clonic seizures. Since AMPAR activation leads to extracellular alkaline shifts, it is likely that the responsiveness to PER in the epileptic hippocampus may be relevant to astroglial TASK-1 regulation, which has been unreported. In the present study, we found that PER ameliorated astroglial TASK-1 upregulation in responders (whose seizure activities were responsive to PER), but not non-responders (whose seizure activities were not responsive to PER), in chronic epilepsy rats. ML365 (a selective TASK-1 inhibitor) diminished astroglial TASK-1 expression and seizure duration in non-responders to PER. ML365 co-treatment with PER decreased spontaneous seizure activities in non-responders to PER. These findings suggest that deregulation of astroglial TASK-1 upregulation may participate in the responsiveness to PER, and that this may be a potential target to improve the efficacies of PER.
Metabolic Reprogramming and Potential Therapeutic Targets in Lymphoma
Authors: Pang Yuyang , Lu Tingxun , Xu-Monette Zijun Y. , Young Ken H.
Published: March 2023

Lymphoma is a heterogeneous group of diseases that often require their metabolism program to fulfill the demand of cell proliferation. Features of metabolism in lymphoma cells include high glucose uptake, deregulated expression of enzymes related to glycolysis, dual capacity for glycolytic and oxidative metabolism, elevated glutamine metabolism, and fatty acid synthesis. These aberrant metabolic changes lead to tumorigenesis, disease progression, and resistance to lymphoma chemotherapy. This metabolic reprogramming, including glucose, nucleic acid, fatty acid, and amino acid metabolism, is a dynamic process caused not only by genetic and epigenetic changes, but also by changes in the microenvironment affected by viral infections. Notably, some critical metabolic enzymes and metabolites may play vital roles in lymphomagenesis and progression. Recent studies have uncovered that metabolic pathways might have clinical impacts on the diagnosis, characterization, and treatment of lymphoma subtypes. However, determining the clinical relevance of biomarkers and therapeutic targets related to lymphoma metabolism is still challenging. In this review, we systematically summarize current studies on metabolism reprogramming in lymphoma, and we mainly focus on disorders of glucose, amino acids, and lipid metabolisms, as well as dysregulation of molecules in metabolic pathways, oncometabolites, and potential metabolic biomarkers. We then discuss strategies directly or indirectly for those potential therapeutic targets. Finally, we prospect the future directions of lymphoma treatment on metabolic reprogramming.
Genome-Wide Analysis of Antigen 43 (Ag43) Variants: New Insights in Their Diversity, Distribution and Prevalence in Bacteria
Authors: Ageorges Valentin , Wawrzyniak Ivan , Ruiz Philippe , Bicep Cédric , Zorgani Mohamed A. , Paxman Jason J. , Heras Begoña , Henderson Ian R. , Leroy Sabine , Bailly Xavier , Sapountzis Panagiotis , Peyretaillade Eric , Desvaux Mickaël
Published: March 2023

Antigen 43 (Ag43) expression induces aggregation and biofilm formation that has consequences for bacterial colonisation and infection. Ag43 is secreted through the Type 5 subtype “a” secretion system (T5aSS) and is a prototypical member of the family of self-associating autotransporters (SAATs). As a T5aSS protein, Ag43 has a modular architecture comprised of (i) a signal peptide, (ii) a passenger domain that can be subdivided into three subdomains (SL, EJ, and BL), (iii) an autochaperone (AC) domain, and (iv) an outer membrane translocator. The cell-surface SL subdomain is directly involved in the “Velcro-handshake” mechanism resulting in bacterial autoaggregation. Ag43 is considered to have a ubiquitous distribution in E. coli genomes and many strains harbour multiple agn43 genes. However, recent phylogenetic analyses indicated the existence of four distinct Ag43 classes exhibiting different propensities for autoaggregation and interactions. Given the knowledge of the diversity and distribution of Ag43 in E. coli genomes is incomplete, we have performed a thorough in silico investigation across bacterial genomes. Our comprehensive analyses indicate that Ag43 passenger domains cluster in six phylogenetic classes associated with different SL subdomains. The diversity of Ag43 passenger domains is a result of the association of the SL subtypes with two different EJ-BL-AC modules. We reveal that agn43 is almost exclusively present among bacterial species of the Enterobacteriaceae family and essentially in the Escherichia genus (99.6%) but that it is not ubiquitous in E. coli. The gene is typically present as a single copy but up to five copies of agn43 with different combinations of classes can be observed. The presence of agn43 as well as its different classes appeared to differ between Escherichia phylogroups. Strikingly, agn43 is present in 90% of E. coli from E phylogroup. Our results shed light on Ag43 diversity and provide a rational framework for investigating its role in E. coli ecophysiology and physiopathology.
Novel Approach to the Treatment of Neuropathic Pain Using a Combination with Palmitoylethanolamide and Equisetum arvense L. in an In Vitro Study
Authors: Ruga Sara , Galla Rebecca , Ferrari Sara , Invernizzi Marco , Uberti Francesca
Published: March 2023

Neuropathic pain is a typical patient disorder resulting from damage and dysfunction of the peripheral neuraxis. Injury to peripheral nerves in the upper extremities can result in a lifelong reduction in quality of life and a devastating loss of sensory and motor function. Since some standard pharmaceutical therapies can cause dependence or intolerance, nonpharmacological treatments have gained great interest in recent years. In this context, the beneficial effects of a new combination of palmitoylethanolamide and Equisetum arvense L. are evaluated in the present study. The bioavailability of the combination was initially analyzed in a 3D intestinal barrier simulating oral intake to analyze its absorption/biodistribution and exclude cytotoxicity. In a further step, a 3D nerve tissue model was performed to study the biological effects of the combination during the key mechanisms leading to peripheral neuropathy. Our results demonstrate that the combination successfully crossed the intestinal barrier and reached the target site, modulating the nerve recovery mechanism after Schwann cell injury and offering the initial response of relieving pain. This work supported the efficacy of palmitoylethanolamide and Equisetum arvense L. in reducing neuropathy and modifying the major pain mechanisms, outlining a possible alternative nutraceutical approach.
Sleep-Disordered Breathing and Chronic Respiratory Infections: A Narrative Review in Adult and Pediatric Population
Authors: Faverio Paola , Zanini Umberto , Monzani Anna , Parati Gianfranco , Luppi Fabrizio , Lombardi Carolina , Perger Elisa
Published: March 2023

Sleep-disordered breathing (SDB) comprises different diseases characterized by abnormal respiratory patterns during sleep including obstructive sleep apnea. SDB prevalence and impact in patients with chronic respiratory infections have been only marginally studied. The purpose of this narrative review is to report the prevalence and impact of SDB in chronic respiratory infections, including cystic fibrosis (CF), bronchiectasis and mycobacterial infections, and explore the possible pathophysiological mechanisms. Common pathophysiological mechanisms, underlying SDB onset in all chronic respiratory infections, include inflammation, which plays a central role, chronic nocturnal cough and pain, excessive production of mucous plugs, presence of obstructive and/or restrictive ventilatory impairment, upper airways involvement, and comorbidities, such as alteration of nutritional status. SDB may affect about 50% of patients with bronchiectasis. The severity of the disease, e.g., patients colonized with P. aeruginosa and frequent exacerbators, as well as comorbidities, such as chronic obstructive pulmonary disease and primary ciliary dyskinesia, may impact SDB onset. SDB may also frequently complicate the clinical course of both children and adults with CF, impacting the quality of life and disease prognosis, suggesting that their routine assessment should be incorporated into the clinical evaluation of patients from the first stages of the disease regardless of suggestive symptoms, in order to avoid late diagnosis. Finally, although the prevalence of SDB in patients with mycobacterial infections is uncertain, extrapulmonary manifestations, particularly nasopharyngeal locations, and concomitant symptoms, such as body pain and depression, may act as atypical predisposing factors for their development.
Tamoxifen Modulates the Immune Landscape of the Tumour Microenvironment: The Paired Siglec-5/14 Checkpoint in Anti-Tumour Immunity in an In Vitro Model of Breast Cancer
Authors: Wielgat Przemyslaw , Rogowski Karol , Czarnomysy Robert , Wawrusiewicz-Kurylonek Natalia , Narejko Karolina , Bielawski Krzysztof , Car Halina
Published: March 2023

Since the role of sialome–Siglec axis has been described as a regulatory checkpoint of immune homeostasis, the promotion of stimulatory or inhibitory Siglec-related mechanisms is crucial in cancer progression and therapy. Here, we investigated the effect of tamoxifen on the sialic acid–Siglec interplay and its significance in immune conversion in breast cancer. To mimic the tumour microenvironment, we used oestrogen-dependent or oestrogen-independent breast cancer cells/THP-1 monocytes transwell co-cultures exposed to tamoxifen and/or β-estradiol. We found changes in the cytokine profiles accompanied by immune phenotype switching, as measured by the expression of arginase-1. The immunomodulatory effects of tamoxifen in THP-1 cells occurred with the altered SIGLEC5 and SIGLEC14 genes and the expression of their products, as confirmed by RT-PCR and flow cytometry. Additionally, exposure to tamoxifen increased the binding of Siglec-5 and Siglec-14 fusion proteins to breast cancer cells; however, these effects appeared to be unassociated with oestrogen dependency. Our results suggest that tamoxifen-induced alterations in the immune activity of breast cancer reflect a crosstalk between the Siglec-expressing cells and the tumour’s sialome. Given the distribution of Siglec-5/14, the expression profile of inhibitory and activatory Siglecs in breast cancer patients may be useful in the verification of therapeutic strategies and predicting the tumour’s behaviour and the patient’s overall survival.
Contribution of Blood Vessel Activation, Remodeling and Barrier Function to Inflammatory Bowel Diseases
Authors: Britzen-Laurent Nathalie , Weidinger Carl , Stürzl Michael
Published: March 2023

Inflammatory bowel diseases (IBDs) consist of a group of chronic inflammatory disorders with a complex etiology, which represent a clinical challenge due to their often therapy-refractory nature. In IBD, inflammation of the intestinal mucosa is characterized by strong and sustained leukocyte infiltration, resulting in the loss of epithelial barrier function and subsequent tissue destruction. This is accompanied by the activation and the massive remodeling of mucosal micro-vessels. The role of the gut vasculature in the induction and perpetuation of mucosal inflammation is receiving increasing recognition. While the vascular barrier is considered to offer protection against bacterial translocation and sepsis after the breakdown of the epithelial barrier, endothelium activation and angiogenesis are thought to promote inflammation. The present review examines the respective pathological contributions of the different phenotypical changes observed in the microvascular endothelium during IBD, and provides an overview of potential vessel-specific targeted therapy options for the treatment of IBD.
Acoustic Stress Induces Opposite Proliferative/Transformative Effects in Hippocampal Glia
Authors: Cruz-Mendoza Fernando , Luquin Sonia , García-Estrada Joaquín , Fernández-Quezada David , Jauregui-Huerta Fernando
Published: March 2023

The hippocampus is a brain region crucially involved in regulating stress responses and highly sensitive to environmental changes, with elevated proliferative and adaptive activity of neurons and glial cells. Despite the prevalence of environmental noise as a stressor, its effects on hippocampal cytoarchitecture remain largely unknown. In this study, we aimed to investigate the impact of acoustic stress on hippocampal proliferation and glial cytoarchitecture in adult male rats, using environmental noise as a stress model. After 21 days of noise exposure, our results showed abnormal cellular proliferation in the hippocampus, with an inverse effect on the proliferation ratios of astrocytes and microglia. Both cell lineages also displayed atrophic morphologies with fewer processes and lower densities in the noise-stressed animals. Our findings suggest that, stress not only affects neurogenesis and neuronal death in the hippocampus, but also the proliferation ratio, cell density, and morphology of glial cells, potentially triggering an inflammatory-like response that compromises their homeostatic and repair functions.
Sinapic Acid Co-Amorphous Systems with Amino Acids for Improved Solubility and Antioxidant Activity
Authors: Garbiec Ewa , Rosiak Natalia , Tykarska Ewa , Zalewski Przemysław , Cielecka-Piontek Judyta
Published: March 2023

The objective of this study was to obtain co-amorphous systems of poorly soluble sinapic acid using amino acids as co-formers. In order to assess the probability of the interaction of amino acids, namely, arginine, histidine, lysine, tryptophan, and proline, selected as co-formers in the amorphization of sinapic acid, in silico studies were carried out. Sinapic acid systems with amino acids in a molar ratio of 1:1 and 1:2 were obtained using ball milling, solvent evaporation, and freeze drying techniques. X-ray powder diffraction results confirmed the loss of crystallinity of sinapic acid and lysine, regardless of the amorphization technique used, while remaining co-formers produced mixed results. Fourier-transform infrared spectroscopy analyses revealed that the co-amorphous sinapic acid systems were stabilized through the creation of intermolecular interactions, particularly hydrogen bonds, and the potential formation of salt. Lysine was selected as the most appropriate co-former to obtain co-amorphous systems of sinapic acid, which inhibited the recrystallization of sinapic acid for a period of six weeks in 30 °C and 50 °C. Obtained co-amorphous systems demonstrated an enhancement in dissolution rate over pure sinapic acid. A solubility study revealed a 12.9-fold improvement in sinapic acid solubility after introducing it into the co-amorphous systems. Moreover, a 2.2-fold and 1.3-fold improvement in antioxidant activity of sinapic acid was observed with respect to the ability to neutralize the 2,2-diphenyl-1-picrylhydrazyl radical and to reduce copper ions, respectively.
Secretory Phospholipase A2 and Interleukin-6 Levels as Predictive Markers of the Severity and Outcome of Patients with COVID-19 Infections
Authors: Urazov Stanislav , Chernov Alexandr , Popov Oleg , Klenkova Natalya , Sushentseva Natalya , Polkovnikova Irina , Apalko Svetlana , Kislyuk Kseniya , Pavlovich Dragana , Ivanov Andrey , Shcherbak Sergey
Published: March 2023

Coronavirus disease (COVID-19) has become a global pandemic. COVID-19 patients need immediate diagnosis and rehabilitation, which makes it urgent to identify new protein markers for a prognosis of the severity and outcome of the disease. The aim of this study was to analyze the levels of interleukin-6 (IL-6) and secretory phospholipase (sPLA2) in the blood of patients regarding the severity and outcome of COVID-19 infection. The study included clinical and biochemical data obtained from 158 patients with COVID-19 treated at St. Petersburg City Hospital No. 40. A detailed clinical blood test was performed on all patients, as well as an assessment of IL-6, sPLA2, aspartate aminotransferase (AST), total protein, albumin, lactate dehydrogenase (LDH), APTT, fibrinogen, procalcitonin, D-dimer, C-reactive protein (CRB), ferritin, and glomerular filtration rate (GFR) levels. It was found that the levels of PLA2, IL-6, APTV, AST, CRP, LDH, IL-6, D-dimer, and ferritin, as well as the number of neutrophils, significantly increased in patients with mild to severe COVID-19 infections. The levels of IL-6 were positively correlated with APTT; the levels of AST, LDH, CRP, D-dimer, and ferritin; and the number of neutrophils. The increase in the level of sPLA2 was positively correlated with the levels of CRP, LDH, D-dimer, and ferritin, the number of neutrophils, and APTT, and negatively correlated with the levels of GFR and lymphocytes. High levels of IL-6 and PLA2 significantly increase the risk of a severe course by 13.7 and 2.24 times, and increase the risk of death from COVID-19 infection by 14.82 and 5.32 times, respectively. We have shown that the blood levels of sPLA2 and IL-6 increase in cases which eventually result in death and when patients are transferred to the ICU (as the severity of COVID-19 infection increases), showing that IL-6 and sPLA2 can be considered as early predictors of aggravation of COVID-19 infections.
New Carbonate-Based Materials and Study of Cytotoxic Capacity in Cancer Cells
Authors: Niza-Pérez Nayara , Quiroz-Troncoso Josefa , Alegría-Aravena Nicolás , Gómez-Ruiz Santiago , Díaz-García Diana , Ramírez-Castillejo Carmen
Published: March 2023

Calcium carbonate, one of the most commonly found biominerals produced by organisms, has shown great potential for the development of systems with biological applications due to its excellent biocompatibility, biodegradability, and simple chemical composition. Here, we focus on the synthesis of various carbonate-based materials with vaterite phase control and their subsequent functionalization for applications in treating glioblastoma, one of the most limiting tumors currently without effective treatments. The incorporation of l-cysteine into the systems increased cell selectivity while the incorporation of manganese supplied the materials with cytotoxic capacity. Extensive characterization of the systems by infrared spectroscopy, ultraviolet-visible spectroscopy, X-ray diffraction, X-ray fluorescence, and transmission electron microscopy confirmed the incorporation of the different fragments causing selectivity and cytotoxicity to the systems. To verify their therapeutic activity, the vaterite-based materials were tested in the CT2A cell line (murine glioma) and compared to SKBR3 (breast cancer) and HEK-293T (human kidney) cell lines. These studies on the cytotoxicity of the materials have shown promising results that can encourage future in vivo studies in glioblastoma models.
Interest of Procalcitonin in ANCA Vasculitides for Differentiation between Flare and Infections
Authors: Poirot-Seynaeve Xavier , Smets Perrine , Pereira Bruno , Olagne Louis , Stievenart Julien , Sapin Vincent , Aumaitre Olivier , Andre Marc , Trefond Ludovic
Published: March 2023

Procalcitonin (PCT) was established as a biomarker to discriminate bacterial infections from other proinflammatory conditions. Our objective was to determine whether PCT is effective in differentiating infection from antineutrophil-cytoplasmic-antibody (ANCA)-associated vasculitides (AAV) flare. In this retrospective, case-control study, PCT and other inflammatory biomarkers of patients with AAV relapse (relapsing group) were compared to infected AAV patients (infected group). In our population of 74 patients with AAV, PCT was significantly higher in the infected group than in the relapsing group (0.2 µg/L [0.08; 0.935] vs. 0.09 µg/L [0.05; 0.2], p < 0.001). Sensitivity and specificity were 53.4% and 73.6%, respectively, for an ideal threshold of 0.2 µg/L. C-reactive protein (CRP) was significantly higher in cases of infection than in relapse (64.7 mg/L [25; 131] vs. 31.5 mg/L, [10.6; 120], p = 0.001). Sensitivity and specificity for infections were 94.2% and 11.3%, respectively. Fibrinogen, white blood cell count, eosinophil count, and neutrophil count were not significantly different. In the multivariate analysis, the relative risk of infection was 2 [1.02; 4.5] (p = 0.04) for a PCT above 0.2 µg/L. In AAV, PCT may be useful for discriminating between infections and flare in patients suffering from AAVs.
Imaging Concrete Structures with Ultrasonic Shear Waves—Technology Development and Demonstration of Capabilities
Authors: Dinh Kien , Tran Khiem , Gucunski Nenad , Ferraro Christopher C. , Nguyen Tu
Published: March 2023

Since 1987 when dry-point-contact (DPC) transducers were invented in the USSR, ultrasonic shear wave devices based on those transducers have been commercialized and have become one of the most effective technologies for imaging concrete. That said, the objectives of this paper are (1) to provide a brief review of the historical development of these powerful devices and (2) to provide a comprehensive assessment of their capabilities in imaging internal entities and structural defects. Regarding the former, the paper presents the context that gave birth to DPC technology and different generations of ultrasonic shear wave devices for concrete inspection. For the latter, one of the state-of-the-art ultrasonic shear wave devices (MIRA 3D) was used to collect data on concrete specimens with different built-in flaws/defects. Those data are then visualized with a commonly used data processing algorithm, the so-called synthetic aperture focusing technique (SAFT). Finally, based on the resulting images, the capabilities of the device are discussed in detail for each concrete imaging problem. A main limitation of ultrasonic shear wave technique for concrete inspection is that it requires a significant amount of time and effort for data collection.
The Structure of the Female Genital System of the Diving Beetle Scarodytes halensis (Fabricius, 1787) (Hydroporinae, Dytiscidae), and the Organization of the Spermatheca and the Spermathecal Gland Complex
Authors: Dallai Romano , Mercati David , Fanciulli Pietro P. , Lupetti Pietro
Published: March 2023

The fine structure of the female reproductive organs of the diving beetle Scarodytes halensis has been described, with particular attention to the complex organization of the spermatheca and the spermathecal gland. These organs are fused in a single structure whose epithelium is involved in a quite different activity. The secretory cells of the spermathecal gland have a large extracellular cistern with secretions; duct-forming cells, by their efferent duct, transport the secretions up to the apical cell region where they are discharged into the gland lumen. On the contrary, the spermatheca, filled with sperm, has a quite simple epithelium, apparently not involved in secretory activity. The ultrastructure of the spermatheca is almost identical to that described in a closely related species Stictonectes optatus. Sc. halensis has a long spermathecal duct connecting the bursa copulatrix to the spermatheca–spermathecal gland complex. This duct has a thick outer layer of muscle cells. Through muscle contractions, sperm can be pushed forwarding up to the complex of the two organs. A short fertilization duct allows sperm to reach the common oviduct where eggs will be fertilized. The different organization of the genital systems of Sc. halensis and S. optatus might be related to a different reproductive strategy of the two species.
The Detection of Dental Pathologies on Periapical Radiographs—Results from a Reliability Study
Authors: Meusburger Theresa , Wülk Annika , Kessler Andreas , Heck Katrin , Hickel Reinhard , Dujic Helena , Kühnisch Jan
Published: March 2023

(1) Background: Caries, periapical lesions, periodontal bone loss (PBL), and endo-perio lesions are common dental findings that require an accurate diagnostic assessment to allow appropriate disease management. The purpose of this reliability study was to compare the inter- and intra-rater reliability for the detection of the above-mentioned pathologies on periapical radiographs. (2) Methods: Fourteen dentists (three with more than two years and eleven with less than two years of work experience) participated in a training workshop prior to data acquisition. A total of 150 radiographs were assessed by all raters in two rounds. Cohen’s Kappa (CK) values and a binary logistic regression were calculated. (3) Results: The reliability was found in a moderate and substantial range of agreement: caries (mean inter-rater CK value/first round 0.704/mean inter-rater CK value/second round 0.659/mean intra-rater CK value 0.778), periapical lesions (0.643/0.611/0.768), PBL (0.454/0.482/0.739) and endo-perio lesion (0.702/0.689/0.840). The regression model revealed a significant influence of the clinical experience, and furthermore, periapical pathologies and PBL were identified less reliably in comparison to caries and endo-perio lesions. (4) Conclusions: The dentist’s ability to detect the chosen pathologies was linked with significant differences. Periapical lesions and PBL were identified less reliably than caries and endo-perio lesions.
Lower Patient Height and Weight Are Predisposing Factors for Complex Radial Arterial Catheterization
Authors: Huber Kristine , Menzenbach Jan , Velten Markus , Kim Se-Chan , Hilbert Tobias
Published: March 2023

Background: Radial artery (RA) catheterization for invasive blood pressure monitoring is often performed via palpation, and an ultrasound is used secondarily only in case of multiple unsuccessful attempts. Although more elaborate, it has been shown that primary ultrasound-guided catheterization may be advantageous compared with palpation. The aim of this study was to identify factors associated with difficult RA catheterization. Methods: Left RA ultrasound assessments were performed in patients with indicated invasive blood pressure monitoring the day before surgery. RA catheterization was performed by personnel blinded to the ultrasound results. Based on the number of attempts needed for successful catheter placement, the cohort was divided into uncomplicated (group 1) and difficult (more than one attempt, group 2) catheterization cases. Cases subjected to primary ultrasound were excluded from the analysis. Results: Body weight, height and surface area (BSA) of patients in group 2 (n = 16) were significantly lower than those of patients in group 1 (n = 25), and internal RA diameters were significantly smaller in group 2 patients. In the whole cohort, BSA was significantly associated with distal and proximal internal RA diameters. In contrast, no differences were observed in the skin-to-artery distance, the longitudinal axis deviation (kinking) or blood flow velocity. Median time to successful catheterization was 77 (47–179) s. Prolonged time needed for cannulation was significantly associated with lower body weight, BMI and BSA, and with reduced distal and proximal internal RA diameter. Conclusions: RA catheterization performed through pulse palpation may be difficult, especially in adult patients with lower body weight and height, due to reduced arterial diameters. Initial use of ultrasound in these patients may reduce first-attempt failure, preventing procedural delays and patient discomfort.
Incidence and Predictors of Incidental Biochemical and Radiologic Pancreatic Alterations Following Uncomplicated ERCP
Authors: Chau Millie , Samnani Sunil , Bazerbachi Fateh , Mirakhur Anirudh , Ruan Yibing , Howarth Megan , Bass Sydney , Cole Martin J. , Lei Yang , Li Suqing , Turbide Christian , Mohamed Rachid , Brenner Darren R. , Heitman Steven J. , Elmunzer B. Joseph , Forbes Nauzer
Published: March 2023

Background: Despite post-ERCP pancreatitis (PEP) being a major focus of outcomes research in endoscopic retrograde cholangiopancreatography (ERCP), little is known regarding the frequency with which asymptomatic biochemical and/or radiologic pancreatic alterations occur in patients following ERCP. Methods: Adult inpatients undergoing ERCP were identified from a prospective ERCP registry. Patients with any abdominal pain, confirmed PEP, or pancreatitis or abnormal pancreatic enzymes preceding ERCP were excluded. Primary outcomes were asymptomatic lipase elevation on bloodwork within 24 h of ERCP or asymptomatic cross-sectional imaging findings consistent with acute pancreatitis in the absence of clinical PEP within 14 days. Multinomial logistic regression and multiple logistic regression were used to examine associations between exposures and lipase levels and between PEP or imaging findings, respectively. Results: In total, 646 and 187 patients were analyzed as part of the biochemical and radiologic cohorts, respectively. A total of 26.0% of patients had asymptomatic elevations in lipase above the upper limit of normal (ULN) within 24 h, and 9.4% had elevations >3× ULN. A total of 20.9% of patients had incidental findings of enlargement, inflammation/edema/fat stranding, peri-pancreatic fluid collections, and/or necrosis on cross-sectional imaging within 14 days. Pancreatic contrast injection was associated with higher odds of asymptomatic lipasemia (adjusted odds ratio, AOR, 7.22; 95% confidence intervals, CI, 1.13 to 46.02), as was the use of the double-wire technique (AOR 15.74; 95% 1.15 to 214.74) and placement of a common bile duct stent (AOR 4.19; 95% CI 1.37 to 12.77). Over 10 cannulation attempts were associated with the presence of one or more radiologic finding(s) (AOR 33.95; 95% CI 1.64, to 704.13). Conclusions: Significant rates of incidental biochemical and/or radiologic pancreatic abnormalities are present following ERCP. Clinicians should be aware of our findings to minimize misclassification and better direct healthcare utilization.
One-Year Review in Cardiac Arrest: The 2022 Randomized Controlled Trials
Authors: Penna Alessio , Magliocca Aurora , Merigo Giulia , Stirparo Giuseppe , Silvestri Ivan , Fumagalli Francesca , Ristagno Giuseppe
Published: March 2023

Cardiac arrest, one of the leading causes of death, accounts for numerous clinical studies published each year. This review summarizes the findings of all the randomized controlled clinical trials (RCT) on cardiac arrest published in the year 2022. The RCTs are presented according to the following categories: out-of- and in-hospital cardiac arrest (OHCA, IHCA) and post-cardiac arrest care. Interestingly, more than 80% of the RCTs encompassed advanced life support and post-cardiac arrest care, while no studies focused on the treatment of IHCA, except for one that, however, explored the temperature control after resuscitation in this population. Surprisingly, 9 out of 11 RCTs led to neutral results demonstrating equivalency between the newly tested interventions compared to current practice. One trial was negative, showing that oxygen titration in the immediate pre-hospital post-resuscitation period decreased survival compared to a more liberal approach. One RCT was positive and introduced new defibrillation strategies for refractory cardiac arrest. Overall, data from the 2022 RCTs discussed here provide a solid basis to generate new hypotheses to be tested in future clinical studies.
Elevated Blood Alcohol Concentration Is Associated with Improved Clinical Outcomes of Intravenous Thrombolysis Treatment in Acute Ischemic Stroke Patients—A Retrospective Study
Authors: Árokszállási Tamás , Balogh Eszter , Orbán-Kálmándi Rita , Pásztor Máté , Árokszállási Anita , Nagy Edit Boglárka , Belán Ivett , May Zsolt , Csépány Tünde , Csiba László , Bagoly Zsuzsa , Oláh László
Published: March 2023

Background: Intravenous thrombolysis (IVT) improves acute ischemic stroke (AIS) outcomes, but with limited success. In addition, ethanol potentiates the effect of r-tPA in ischemia models. Methods: The effect of acute alcohol consumption on IVT outcomes was investigated in a retrospective cohort study. AIS patients with detectable blood alcohol concentration (BAC) during IVT were included (alcohol group; n = 60). For each case, 3 control subjects who underwent IVT but denied alcohol consumption were matched in terms of age, sex, affected brain area, and stroke severity. Outcomes were determined using the NIHSS at 7 days and the modified Rankin scale (mRS) at 90 days. Results: Patients were younger and had a less severe stroke than in a standard stroke study. Favorable long-term outcomes (mRS 0–2) occurred significantly more frequently in the alcohol group compared to controls (90% vs. 63%, p < 0.001). However, the rates of hemorrhagic transformation were similar. Multiple logistic regression models identified elevated BAC as a significant protective factor against unfavorable short-term (OR: 0.091, 95% CI: 0.036–0.227, p < 0.001) and long-term outcomes (OR: 0.187, 95% CI: 0.066–0.535, p = 0.002). In patients with BAC > 0.2%, significantly lower NIHSS was observed at 3 and 7 days after IVT vs. in those with 0.01–0.2% ethanol levels. Conclusion: Elevated BAC is associated with improved outcomes in IVT-treated AIS without affecting safety.
A National Survey of Children, Adults, and the Elderly in the Fourth Wave of the COVID-19 Pandemic to Compare Acute and Post-COVID-19 Conditions in Saudi Arabia
Authors: Alsagheir Aeshah , Amer Samer , Alzubaidi Lamya , Alenezi Fasial , Alamaa Tareef , Asiri Abdullah
Published: March 2023

Background: The fight against COVID-19 appears to extend beyond screening and treatment of acute diseases to its medium- and long-term health consequences. Little is known about the epidemiology and the determinants of developing post-COVID-19 conditions (PCCs) among children. The aims of this study were to explore and determine the prevalence of PCCs among three age groups (children and adolescents, adults, and the elderly), and study the predictors of participants’ return to their pre-COVID-19 health status among COVID-19 patients at least four weeks after they got sick, from February to 15 July 2022. Methods: This comparison survey study targeted 12,121 COVID-19 patients who fulfilled the selection criteria from the national register system and received a virtual assessment from the Medical Consultation Call Center (937), which was conducted by a well-trained family physician using a validated, well-structured assessment tool. The collected data were coded and analyzed using appropriate tests. Results: Out of the 12,121 recovered COVID-19 patients who received the virtual assessment calls, only 5909 (48.8%) agreed and completed the assessment. The majority of participants (4973, or 84.2%) reported no PCCs. The most common PCCs among young people were a cough, dyspnea, fatigue, and loss of appetite or weight loss, while among the elderly they were a cough, dyspnea, fatigue, stomachaches, poor concentration, sleep disturbance, and recurrent fever. Most post-COVID-19 cases require nothing more than reassurance and health education as only 384 (6.5%) required referral to primary health care centers (PHCCs.) The severity of COVID-19 infection, age group, sex, vaccination status, and body mass index were significant predictors for returning to the pre-infection health status and the required referral was significantly related to many factors. Conclusions: The comparison of children, adults, and the elderly with regard to the acute and post-COVID-19 conditions in Saudi Arabia in terms of the clinical health assessment and the required management plans showed significant differences.
Comparison between Intraocular Pressure Profiles over 24 and 48 h in the Management of Glaucoma
Authors: Keye Philip , Böhringer Daniel , Anton Alexandra , Reinhard Thomas , Lübke Jan
Published: March 2023

(1) Background: Due to significant variation, sporadic IOP measurements often fail to correctly assess the IOP situation in glaucoma patients. Thus, diurnal-nocturnal IOP profiles can be used as a diagnostic tool. The purpose of this study is to determine the additional diagnostic value of prolonged IOP profiles. (2) Methods: All diagnostic 48 h IOP profiles from a large university hospital, between 2017 and 2019, were reviewed. Elevated IOP > 21 mmHg, IOP variation > 6 mmHg and nocturnal IOP peaks were defined as IOP events of interest and counted. The analysis was repeated for the first 24 h of every IOP profile only. The Chi2 test was used for statistical analysis. (3) Results: 661 IOP profiles were included. Specifically, 59% of the 48 h IOP profiles revealed IOP values above 21 mmHg, and 87% showed IOP fluctuation greater than 6 mmHg. Nocturnal peaks in the supine position could be observed in 51% of the patients. In the profiles censored for the first 24 h, the fractions were 50%, 71% and 48%, (p < 0.01, p < 0.01 and p = 0.12) respectively. (4) Conclusions: the 48 h IOP profiles identified more patients with IOP events of interest than the 24 h IOP profiles. The additional diagnostic value must be weighed against the higher costs.
THMC Fully Coupled Model of Natural Gas Hydrate under Damage Effect and Parameter Sensitivity Analysis
Authors: Qiu Yue , Wang Xiangfu , Wang Zhaofeng , Liang Wei , Zhao Tongbin
Published: March 2023

In order to study the influence of damage on the gas production of natural gas hydrate, a multi-physical field theoretical model considering damage effect and coupling thermal-hydraulic-mechanical-chemical (THMC) was established by theoretical analysis and numerical simulation. The THMC model establishes the relationship between the elastic modulus of hydrate sediment and hydrate saturation during the whole process of hydrate decomposition. The THC (thermal-hydraulic-chemical) and THMC fully coupled models not considering or considering the damage effect were compared and analyzed, and the reliability of the THMC fully coupled model was verified. On this basis, the deformation, permeability and damage of hydrate sediments under different initial hydrate saturations and different depressurization amplitudes, as well as the hydrate gas production rate and cumulative gas production, are analyzed. The results showed that higher initial hydrate saturation inhibited the development of damage, maintained stable gas production and increased cumulative gas production. Larger depressurization promoted damage and increased cumulative gas production, but it was easy to cause stability problems.
Interpolation-Based Inference of Vessel Trajectory Waypoints from Sparse AIS Data in Maritime
Authors: Zaman Bakht , Marijan Dusica , Kholodna Tetyana
Published: March 2023

The availability of automatic identification system (AIS) data for tracking vessels has paved the way for improvements in maritime safety and efficiency. However, one of the main challenges in using AIS data is often the low quality of the data. Practically, AIS-based trajectory data of vessels are available at irregular time intervals; consequently, large temporal gaps often exist in the historical AIS data. Meanwhile, certain tasks such as waypoint detection using historical data, which involves finding locations along the trajectory where the vessel changes its course (and possibly speed, acceleration, etc.), require AIS messages with a high temporal resolution. High-resolution AIS data are especially required for waypoint detection in critical areas where vessels maneuver carefully because of, e.g., narrow pathways or the presence of islands. One possible solution to address the problem of insufficient AIS data in vessel trajectories is interpolation. In this paper, we address the problem of detecting waypoints in a single representative trajectory with insufficient data using various interpolation-based methods. To this end, a two-step approach is proposed, in which the trajectories are first interpolated, and then the waypoint detection method is applied to the merged trajectory containing both interpolated and observed AIS messages. The numerical results demonstrate the effectiveness of exploiting various interpolation methods for waypoint detection. Moreover, the results of the numerical experiments show that the proposed methodology is effective for waypoint detection in envisaged settings with insufficient data, and outperforms the competing algorithm.
Automatic Diagnosis of Infectious Keratitis Based on Slit Lamp Images Analysis
Authors: Hu Shaodan , Sun Yiming , Li Jinhao , Xu Peifang , Xu Mingyu , Zhou Yifan , Wang Yaqi , Wang Shuai , Ye Juan
Published: March 2023

Infectious keratitis (IK) is a common ophthalmic emergency that requires prompt and accurate treatment. This study aimed to propose a deep learning (DL) system based on slit lamp images to automatically screen and diagnose infectious keratitis. This study established a dataset of 2757 slit lamp images from 744 patients, including normal cornea, viral keratitis (VK), fungal keratitis (FK), and bacterial keratitis (BK). Six different DL algorithms were developed and evaluated for the classification of infectious keratitis. Among all the models, the EffecientNetV2-M showed the best classification ability, with an accuracy of 0.735, a recall of 0.680, and a specificity of 0.904, which was also superior to two ophthalmologists. The area under the receiver operating characteristics curve (AUC) of the EffecientNetV2-M was 0.85; correspondingly, 1.00 for normal cornea, 0.87 for VK, 0.87 for FK, and 0.64 for BK. The findings suggested that the proposed DL system could perform well in the classification of normal corneas and different types of infectious keratitis, based on slit lamp images. This study proves the potential of the DL model to help ophthalmologists to identify infectious keratitis and improve the accuracy and efficiency of diagnosis.