bluuebunny/crossref_metadata_2025 huggingface dataset:
Human Dermal Decellularized ECM Hydrogels as Scaffolds for 3D In Vitro Skin Aging Models
Authors: Fernandez-Carro Estibaliz , Remacha Ana Rosa , Orera Irene , Lattanzio Giuseppe , Garcia-Barrios Alberto , del Barrio Jesús , Alcaine Clara , Ciriza Jesús
Published: April 2024

Biomaterials play an important role in the development of advancing three dimensional (3D) in vitro skin models, providing valuable insights for drug testing and tissue-specific modeling. Commercial materials, such as collagen, fibrin or alginate, have been widely used in skin modeling. However, they do not adequately represent the molecular complexity of skin components. On this regard, the development of novel biomaterials that represent the complexity of tissues is becoming more important in the design of advanced models. In this study, we have obtained aged human decellularized dermal extracellular matrix (dECM) hydrogels extracted from cadaveric human skin and demonstrated their potential as scaffold for advanced skin models. These dECM hydrogels effectively reproduce the complex fibrillar structure of other common scaffolds, exhibiting similar mechanical properties, while preserving the molecular composition of the native dermis. It is worth noting that fibroblasts embedded within human dECM hydrogels exhibit a behavior more representative of natural skin compared to commercial collagen hydrogels, where uncontrolled cell proliferation leads to material shrinkage. The described human dECM hydrogel is able to be used as scaffold for dermal fibroblasts in a skin aging-on-a-chip model. These results demonstrate that dECM hydrogels preserve essential components of the native human dermis making them a suitable option for the development of 3D skin aging models that accurately represent the cellular microenvironment, improving existing in vitro skin models and allowing for more reliable results in dermatopathological studies.
Treatment Monitoring of a Patient with Synchronous Metastatic Angiosarcoma and Breast Cancer Using ctDNA
Authors: Vannas Christoffer , Escobar Mandy , Österlund Tobias , Andersson Daniel , Mouhanna Pia , Soomägi Amanda , Molin Claes , Wennergren David , Fagman Henrik , Ståhlberg Anders
Published: April 2024

Angiosarcoma is a rare and aggressive type of soft-tissue sarcoma with high propensity to metastasize. For patients with metastatic angiosarcoma, prognosis is dismal and treatment options are limited. To improve the outcomes, identifying patients with poor treatment response at an earlier stage is imperative, enabling alternative therapy. Consequently, there is a need for improved methods and biomarkers for treatment monitoring. Quantification of circulating tumor-DNA (ctDNA) is a promising approach for patient-specific monitoring of treatment response. In this case report, we demonstrate that quantification of ctDNA using SiMSen-Seq was successfully utilized to monitor a patient with metastatic angiosarcoma. By quantifying ctDNA levels using 25 patient-specific mutations in blood plasma throughout surgery and palliative chemotherapy, we predicted the outcome and monitored the clinical response to treatment. This was accomplished despite the additional complexity of the patient having a synchronous breast cancer. The levels of ctDNA showed a superior correlation to the clinical outcome compared with the radiological evaluations. Our data propose a promising approach for personalized biomarker analysis to monitor treatment in angiosarcomas, with potential applicability to other cancers and for patients with synchronous malignancies.
The Differential Effect of Senolytics on SASP Cytokine Secretion and Regulation of EMT by CAFs
Authors: Bogdanova Daria A. , Kolosova Ekaterina D. , Pukhalskaia Tamara V. , Levchuk Ksenia A. , Demidov Oleg N. , Belotserkovskaya Ekaterina V.
Published: April 2024

The tumor microenvironment (TME) plays an essential role in tumor progression and in modulating tumor response to anticancer therapy. Cellular senescence leads to a switch in the cell secretome, characterized by the senescence-associated secretory phenotype (SASP), which may regulate tumorigenesis. Senolytic therapy is considered a novel anticancer strategy that eliminates the deleterious effects of senescent cells in the TME. Here, we show that two different types of senolytic drugs, despite efficiently depleting senescent cells, have opposite effects on cancer-associated fibroblasts (CAFs) and their ability to regulate epithelial–mesenchymal transition (EMT). We found that senolytic drugs, navitoclax and the combination of dasatinib/quercetin, reduced the number of spontaneously senescent and TNF-induced senescent CAFs. Despite the depletion of senescent cells, the combination of dasatinib/quercetin versus navitoclax increased the secretion of the SASP pro-inflammatory cytokine IL-6. This differential effect correlated with the promotion of enhanced migration and EMT in MC38 colorectal cancer cells. Our results demonstrate that some senolytics may have side effects unrelated to their senolytic activity and may promote tumorigenesis. We argue for more careful and extensive studies of the effects of senolytics on various aspects of tumor progression and tumor resistance to therapy before the senolytic strategy is implemented in the clinic.
A Conserved Intramolecular Ion-Pair Plays a Critical but Divergent Role in Regulation of Dimerization and Transport Function among the Monoamine Transporters
Authors: Chen Sixiang , Huang Xingyu , Zhang Xintong , Li Chan , Zhang Yuan-Wei
Published: April 2024

The monoamine transporters, including the serotonin transporter (SERT), dopamine transporter (DAT), and norepinephrine transporter (NET), are the therapeutic targets for the treatment of many neuropsychiatric disorders. Despite significant progress in characterizing the structures and transport mechanisms of these transporters, the regulation of their transport functions through dimerization or oligomerization remains to be understood. In the present study, we identified a conserved intramolecular ion-pair at the third extracellular loop (EL3) connecting TM5 and TM6 that plays a critical but divergent role in the modulation of dimerization and transport functions among the monoamine transporters. The disruption of the ion-pair interactions by mutations induced a significant spontaneous cross-linking of a cysteine mutant of SERT and an increase in cell surface expression but with an impaired specific transport activity. On the other hand, similar mutations of the corresponding ion-pair residues in both DAT and NET resulted in an opposite effect on their oxidation-induced dimerization, cell surface expression, and transport function. Reversible biotinylation experiments indicated that the ion-pair mutations slowed down the internalization of SERT but stimulated the internalization of DAT. In addition, cysteine accessibility measurements for monitoring SERT conformational changes indicated that substitution of the ion-pair residues resulted in profound effects on the rate constants for cysteine modification in both the extracellular and cytoplasmatic substrate permeation pathways. Furthermore, molecular dynamics simulations showed that the ion-pair mutations increased the interfacial interactions in a SERT dimer but decreased it in a DAT dimer. Taken together, we propose that the transport function is modulated by the equilibrium between monomers and dimers on the cell surface, which is regulated by a potential compensatory mechanism but with different molecular solutions among the monoamine transporters. The present study provided new insights into the structural elements regulating the transport function of the monoamine transporters through their dimerization.
Loading of Single Atoms of Iron, Cobalt, or Nickel to Enhance the Electrocatalytic Hydrogen Evolution Reaction of Two-Dimensional Titanium Carbide
Authors: Wang Kaijin , Yu Jing , Liu Qi , Liu Jingyuan , Chen Rongrong , Zhu Jiahui
Published: April 2024

The rational design of advanced electrocatalysts at the molecular or atomic level is important for improving the performance of hydrogen evolution reactions (HERs) and replacing precious metal catalysts. In this study, we describe the fabrication of electrocatalysts based on Fe, Co, or Ni single atoms supported on titanium carbide (TiC) using the molten salt method, i.e., TiC-FeSA, TiC-CoSA, or TiC-NiSA, to enhance HER performance. The introduction of uniformly distributed transition-metal single atoms successfully reduces the overpotential of HERs. Overpotentials of TiC-FeSA at 10 mA cm−2 are 123.4 mV with 61.1 mV dec−1 Tafel slope under acidic conditions and 184.2 mV with 85.1 mV dec−1 Tafel slope under alkaline conditions, which are superior to TiC-NiSA and TiC-CoSA. TiC samples loaded with transition-metal single atoms exhibit high catalytic activity and long stability under acidic and basic conditions. Density functional theory calculations indicate that the introduction of transition-metal single atoms effectively reduces the HER barrier of TiC-based electrocatalysts.
Renin–Angiotensin–Aldosterone System: From History to Practice of a Secular Topic
Authors: Ksiazek Sara H. , Hu Lilio , Andò Sebastiano , Pirklbauer Markus , Säemann Marcus D. , Ruotolo Chiara , Zaza Gianluigi , La Manna Gaetano , De Nicola Luca , Mayer Gert , Provenzano Michele
Published: April 2024

Renin–angiotensin–aldosterone system (RAAS) inhibitors are standard care in patients with hypertension, heart failure or chronic kidney disease (CKD). Although we have studied the RAAS for decades, there are still circumstances that remain unclear. In this review, we describe the evolution of the RAAS and pose the question of whether this survival trait is still necessary to humankind in the present age. We elucidate the benefits on cardiovascular health and kidney disease of RAAS inhibition and present promising novel medications. Furthermore, we address why more studies are needed to establish a new standard of care away from generally prescribing ACEi or ARB toward an improved approach to combine drugs tailored to the needs of individual patients.
Effect of Melatonin on Herpesvirus Type 1 Replication
Authors: Pérez-Martínez Zulema , Boga Jose Antonio , Potes Yaiza , Melón Santiago , Coto-Montes Ana
Published: April 2024

Acute HSV-1 infection is associated with mild symptoms, such as fever and lesions of the mouth, face and skin. This phase is followed by a latency period before reactivation, which is associated with symptoms ranging from ulcers to encephalitis. Despite available anti-HSV-1 drugs, the development of new antiviral agents is sought due to the presence of resistant viruses. Melatonin, a molecule secreted by the pineal gland, has been shown to be an antioxidant, inducer of antioxidant enzymes, and regulator of various biological processes. Clinical trials have explored its therapeutic utility in conditions including infections. This study focuses on melatonin’s role in HSV-1 replication and the underlying mechanisms. Melatonin was found to decrease the synthesis of HSV-1 proteins in infected Vero cells measured by immunofluorescence, indicating an inhibition of HSV-1 replication. Additionally, it regulates the activities of antioxidant enzymes and affects proteasome activity. Melatonin activates the unfolded protein response (UPR) and autophagy and suppresses apoptosis in HSV-1-infected cells. In summary, melatonin demonstrates an inhibitory role in HSV-1 replication by modulating various cellular responses, suggesting its potential utility in the treatment of viral infections.
Improving Blood Vessel Segmentation and Depth Estimation in Laser Speckle Images Using Deep Learning
Authors: Morales-Vargas Eduardo , Peregrina-Barreto Hayde , Fuentes-Aguilar Rita Q. , Padilla-Martinez Juan Pablo , Garcia-Suastegui Wendy Argelia , Ramirez-San-Juan Julio C.
Published: April 2024

Microvasculature analysis is an important task in the medical field due to its various applications. It has been used for the diagnosis and threat of diseases in fields such as ophthalmology, dermatology, and neurology by measuring relative blood flow or blood vessel morphological properties. However, light scattering at the periphery of the blood vessel causes a decrease in contrast around the vessel borders and an increase in the noise of the image, making the localization of blood vessels a challenging task. Therefore, this work proposes integrating known information from the experimental setup into a deep learning architecture with multiple inputs to improve the generalization of a computational model for the segmentation of blood vessels and depth estimation in a single inference step. The proposed R-UNET + ET + LA obtained an intersection over union of 0.944 ± 0.065 and 0.812 ± 0.080 in the classification task for validation (in vitro) and test sets (in vivo), respectively, and a root mean squared error of 0.0085 ± 0.0275 μm in the depth estimation. This approach improves the generalization of current solutions by pre-training with in vitro data and adding information from the experimental setup. Additionally, the method can infer the depth of a blood vessel pixel by pixel instead of in regions as the current state of the art does.
A New Time Series Dataset for Cyber-Threat Correlation, Regression and Neural-Network-Based Forecasting
Authors: Sufi Fahim
Published: April 2024

In the face of escalating cyber threats that have contributed significantly to global economic losses, this study presents a comprehensive dataset capturing the multifaceted nature of cyber-attacks across 225 countries over a 14-month period from October 2022 to December 2023. The dataset, comprising 77,623 rows and 18 fields, provides a detailed chronology of cyber-attacks, categorized into eight critical dimensions: spam, ransomware, local infection, exploit, malicious mail, network attack, on-demand scan, and web threat. The dataset also includes ranking data, offering a comparative view of countries’ susceptibility to different cyber threats. The results reveal significant variations in the frequency and intensity of cyber-attacks across different countries and attack types. The data were meticulously compiled using modern AI-based data acquisition techniques, ensuring a high degree of accuracy and comprehensiveness. Correlation tests against the eight types of cyber-attacks resulted in the determination that on-demand scan and local infection are highly correlated, with a correlation coefficient of 0.93. Lastly, neural-network-based forecasting of these highly correlated factors (i.e., on-demand scan and local infection) reveals a similar pattern of prediction, with an MSE and an MAPE of 1.616 and 80.13, respectively. The study’s conclusions provide critical insights into the global landscape of cyber threats, highlighting the urgent need for robust cybersecurity measures.
Flying Projectile Attitude Determination from Ground-Based Monocular Imagery with a Priori Knowledge
Authors: Chen Huamei , Zhu Zhigang , Tang Hao , Blasch Erik , Pham Khanh D. , Chen Genshe
Published: April 2024

This paper discusses using ground-based imagery to determine the attitude of a flying projectile assuming prior knowledge of its external geometry. It presents a segmentation-based approach to follow the object and evaluates it quantitatively with simulated data and qualitatively with both simulated and real data. Two experimental cases are considered: One assumes reliable target distance measurement from an auxiliary range sensor, while the other assumes no range information. The results show that in the case of an unknown projectile–camera distance, with projectile dimensions of 1.378 m and 0.08 m in length and diameter, the estimated distance, in-plane location, and pitch angle accuracies are about 50 m, 0.15 m, and 6 degrees, respectively. Yaw angle estimation is ambiguous. In the second case, assuming that the projectile–camera distance is known resolves the ambiguity of yaw estimation, resulting in accuracies of about 0.15 m, 3 degrees, and 20 degrees for in-plane location, pitch, and yaw angles, respectively. These accuracies were normalized to a 1-km projectile–camera distance.
Maternal Care Behavior and Its Consequences in Competition
Authors: Li Guang-Yun , Li Yu-Chuang , Liu Huai
Published: April 2024

Parental care behavior has evolved as a life history strategy to improve reproductive success, particularly in organisms facing challenging environments. However, the variation in maternal care, such as egg-guarding behavior in response to the social environment and the associated ecological consequence of competition, remains largely unknown. This study addresses a gap in current knowledge by examining the plasticity of maternal care behavior in the predatory mite C. eruditus and its impact on offspring survival and intra- and interspecific competition. Our results demonstrated that the reproductive females frequently exhibit egg-guarding behaviors, with enhanced maternal care efforts when the interspecific competitor is present. Egg masses are significantly more vulnerable to predation in the absence of maternal care. Guarding females increased egg survival rates and adversely influenced the survival of both con- and heterospecific competitors, with higher mortality rates being detected. Our findings highlight the ecological significance of maternal care behaviors and suggest that releasing C. eruditus and Neoseiulus cucumeris (Oudemans) together is not recommended for pest management in storage products.
The Relationship between Selected Parameters and the Occurrence of Premyopia in a Group of 1155 Children Aged 8 in Northwestern Poland
Authors: Modrzejewska Monika , Durajczyk Magdalena
Published: April 2024

Background: Determination of the number of pupils at risk of developing pre-myopia and selected ophthalmic parameters in a group of 1155 children aged 8. Material: Ophthalmic examinations were performed in Polish 8-year-old, /1518 individuals/; 1155 of whom presented complete data for analysis. There was a total of 554 (47.9%) girls and 602 (52.1%) boys. Examination of the anterior and posterior segment of the eye, evaluation of accommodation, convergence, heterophoria, alignment of the eyeball, muscular balance with ocular mobility in 9 directions of gaze, and spatial vision were tested. Refraction was obtained under cycloplegia. Refractions (spherical equivalent, SE). were categorized as pre-myopia (−0.50 D–+0.75 D), myopia (≤−0.5 D), emmetropia (>−0.5 D to ≤+0.5 D), mildly hyperopia (>+0.5 D to ≤+2.0 D) and hyperopia (>+2.0 D). Data analysis was performed using Statistica 13.5 software: chi-squared, Pearson’s, t-Student, and U Mann–Whitney tests. p-values of <0.05 were considered statistically significant. Results: Pre-myopia was diagnosed in as many as 704 subjects (60.9%) with a similar frequency among both girls—328 (46.6%)—and boys with 376 (53.4%). Conclusions: Current data indicates that the growing group of myopic individuals in many industrialized countries is the sixth most common cause of blindness. Further research is crucial to understand the factors underlying accommodative and binocular mechanisms for myopia development and progression and to make recommendations for targeted interventions to slow the progression of myopia in a group of early school children.
Which Factors Are Associated with Persistence of Depressive and Anxiety Symptoms in Patients Affected by Atopic Dermatitis despite 2-Year Treatment with Dupilumab?
Authors: Ferrucci Silvia Mariel , Tavecchio Simona , Ceresa Alessandro , Angileri Luisa , Berti Emilio , Marzano Angelo Valerio , Buoli Massimiliano
Published: April 2024

Background: Atopic Dermatitis (AD) is a prevalent inflammatory skin disease whose course is often complicated by the presence of concomitant anxiety and depressive disorders. Dupilumab has been demonstrated to be largely effective in AD. The aims of the present study were to (1) to verify the effectiveness of 2-year dupilumab treatment on the depressive and anxiety symptoms of patients affected by AD and (2) to identify predictors of the persistence of psychiatric symptoms despite maintenance treatment with dupilumab. Methods: A total of 331 patients with severe AD were assessed at baseline and at different times over 2 years by a large set of rating scales, including the Eczema Area and Severity Index (EASI), the Hospital Anxiety and Depression Scale (HADS), and the Dermatology Life Quality Index (DLQI). Paired sample t-tests were performed to verify the effectiveness of dupilumab on the severity of AD and mental health items. Two binary logistic regression models were then used to identify the predictors of the persistence of clinically significant depression and anxiety, defined by a score ≥ 8 on each sub-scale of the HADS. Results: After 2 years of treatment with dupilumab, the patients benefited, showing a significant improvement in both the dermatological disease and comorbid depression/anxiety (p < 0.001 for all scales). Overall, 17.5% and 13% of patients, respectively, reported residual depressive and anxiety symptoms after the 2-year treatment with dupilumab. The baseline predictors of the persistence of clinically significant depressive symptoms after the 2-year treatment with dupilumab were found to be a higher body mass index (BMI) (p = 0.012), a lower impact of dermatological disease on quality of life (p = 0.015), and more severe depressive symptoms (p < 0.01), while for anxiety, the only predictor was found to be female gender (p = 0.03). Conclusions: Using a multidisciplinary approach, at baseline, dermatologists should more closely monitor patients who are at a greater risk of maintaining residual psychiatric symptoms despite therapy, such as those with more severe depressive symptoms and those who are overweight.
Navigating Uncertain Waters: First-Trimester Screening’s Role in Identifying Neonatal Complications
Authors: Swiercz Grzegorz , Zmelonek-Znamirowska Anna , Szwabowicz Karol , Armanska Justyna , Detka Karolina , Mlodawska Marta , Mlodawski Jakub
Published: April 2024

Background: Contemporary diagnostic methods aimed at assessing neonatal outcomes predominantly rely on the medical history of pregnant women. Ideally, universal biomarkers indicating an increased risk of delivering infants in poor clinical condition, with a heightened likelihood of requiring hospitalization in a Neonatal Intensive Care Unit (NICU), would be beneficial for appropriately stratifying pregnant women into a high-risk category. Our study evaluated whether biochemical and ultrasonographical markers universally used in first-trimester screenings for non-heritable chromosomal aberrations could serve this purpose. Methods: This study encompassed 1164 patients who underwent first-trimester screening, including patient history, ultrasound examinations, and biochemical tests for pregnancy-associated plasma protein-A (PAPP-A) and the free beta-HCG subunit (fbHCG), from January 2019 to December 2021. The research concentrated on the correlation between these prenatal test results and neonatal outcomes, particularly Apgar scores, umbilical blood pH levels, and the necessity for NICU admission. Results: In our cohort, neonates scoring lower than 8 on the Apgar scale at birth exhibited lower concentrations of PAPP-A in the first trimester, both in raw and normalized values (PAPP-A MoM 0.93 vs. 1.027, p = 0.032). We also observed a higher pulsatility index in the venous duct in the first trimester in full-term neonates born with <8 points on the Apgar scale. Additionally, newborns born with an umbilical blood pH < 7.2 had lower normalized first-trimester PAPP-A concentrations (0.69 vs. 1.01 MoM, p = 0.04). We also noted that neonates requiring NICU hospitalization post-delivery had lower first-trimester bHCG concentrations (0.93 MoM vs. 1.11 MoM, p = 0.03). However, none of the correlations in our study translated into a robust prognostic ability for predicting dichotomous outcomes. All areas under the curve achieved a value < 0.7. Conclusions: Low concentrations of PAPP-A and free bHCG subunit in the first trimester may be associated with poorer clinical and biochemical conditions in neonates post-delivery. However, the relationship is weak and has limited predictive capability. Further research evaluating these relationships is necessary for the appropriate stratification of pregnant women into high-risk categories for neonatological complications.
Pre-Treatment and Post-Treatment I-131 Imaging in Differentiated Thyroid Carcinoma
Authors: Mihailović Jasna
Published: April 2024

Radioiodine imaging in initial perioperative settings, after the total thyroidectomy, includes pre-treatment and post-treatment radioiodine imaging. While the benefit of post-treatment whole-body imaging (PT-WBI) is well established, the role of diagnostic whole-body imaging (dx WBI), prior to radioiodine (I-131) ablative or therapeutic doses, is controversial. Dx WBI has been abandoned in most nuclear medicine centers long ago. Planar low-dose dxWBI provides the volume of postoperative thyroid remnants, but it cannot detect occult metastatic foci in the neck. The modern integrated multimodality, i.e., SPECT/CT imaging, provides three dimensional images and accurate anatomic/metabolic data. This hybrid technology offers better spatial resolution but not better sensitivity. Dx WBI has low theranostic power because of the radioiodine indifference and low detection sensitivity for small-volume nodal disease in the neck. Since dx WBI cannot clarify the paratracheal cervical uptake, thyroid remnants may be easily misinterpreted as nodal disease, leading to a false N upstaging (from N0 stage to N1 stage) in DTC patients. Post-ablation I-131 imaging has a significant role in the initial staging of radioiodine-avid DTC and in the identification of non-radioiodine avid tumors. Additionally, SPECT/CT in the post-treatment setting provides more accurate initial TNM staging and better risk stratification of DTC patients. Post-treatment I-131 imaging is obligatory and must be performed in all DTC patients who receive radioiodine treatment.
Environmental Factors as the Main Hormonal Disruptors of Male Fertility
Authors: Wdowiak Natalia , Wójtowicz Kamila , Wdowiak-Filip Anita , Pucek Weronika , Wróbel Andrzej , Wróbel Jan , Wdowiak Artur
Published: April 2024

Introduction and objective: Many scientific reports confirm a systematic decline in male semen parameters over the last decades. This phenomenon has been observed in all parts of the world, and its occurrence is associated, among others, with the hazardous effects of some environmental factors. The environmental factors for which the adverse effect on male fertility has been proven include water, air, and soil pollution, as well as electromagnetic fields and ionizing radiation. The aim of this article was the evaluation of the effect of selected environmental factors on male reproductive capacity based on an analysis of the current scientific reports. Review methods: A systematic literature review was carried out using three databases: PubMed, EMBASE, and Scopus. The search was limited to the period from 2015 until the end of December 2023. Brief description of the state of knowledge: Environmental factors, such as heavy metals, tobacco smoke, pesticides, dioxins, furans, phthalates, and bisphenols, are well-tested substances that exert an adverse effect on male fertility. A harmful effect of electromagnetic fields and water and air pollution on reproductive functions may be expected; however, this has not been fully proven. Summary: Results obtained by many researchers published to date should evoke great concern regarding the quality of the environment in which we live, as well as fears about the effect of environmental factors not only on male fertility, but also on all aspects of human health. The majority of environmental pollutants affect the male body by causing oxidative stress and through their effect on the endocrine system.
De Ritis Ratio to Predict Clinical Outcomes of Intermediate- and High-Risk Pulmonary Embolisms
Authors: Durak Koray , Nubbemeyer Katharina , Zayat Rashad , Spillner Jan , Dineva Slavena , Kalverkamp Sebastian , Kersten Alexander
Published: April 2024

Background: Abnormal liver function tests can identify severe cardiopulmonary failure. The aspartate transaminase/alanine transaminase (AST/ALT) ratio, or the De Ritis ratio, is commonly used to evaluate acute liver damage. However, its prognostic value in pulmonary embolism (PE) is unknown. Methods: Two cohorts, including patients with intermediate- and high-risk PEs, were established: one with an abnormal baseline AST/ALT ratio (>1) and another with a normal baseline AST/ALT ratio (<1). The primary outcome was a 60-day mortality. Secondary outcomes included peak N-terminal pro-brain-natriuretic-peptide (NT-proBNP) levels, complications, and the need for critical care treatment. To assess the effect of abnormal AST/ALT ratios, inverse probability weighted (IPW) analyses were performed. Results: In total, 230 patients were included in the analysis, and 52 (23%) had an abnormal AST/ALT ratio. After the IPW correction, patients with an abnormal AST/ALT ratio had a significantly higher mortality rate and peak NT-proBNP levels. The relative risks of 60-day mortality, shock development, use of inotropes/vasopressors, mechanical ventilation, and extracorporeal life support were 9.2 (95% confidence interval: 3.3–25.3), 10.1 (4.3–24), 2.7 (1.4–5.2), 2.3 (1.4–3.7), and 5.7 (1.4–23.1), respectively. Conclusions: The baseline AST/ALT ratio can be a predictor of shock, multiorgan failure, and mortality in patients with a pulmonary embolism.
A Novel Intraoperative CT Navigation System for Spinal Fusion Surgery in Lumbar Degenerative Disease: Accuracy and Safety of Pedicle Screw Placement
Authors: Kanno Haruo , Handa Kyoichi , Murotani Motoki , Ozawa Hiroshi
Published: April 2024

Background: In recent years, intraoperative computed tomography (CT) navigation has become widely used for the insertion of pedicle screws in spinal fusion surgery. However, conventional intraoperative CT navigation may be impaired by infrared interference between the infrared camera and surgical instruments, which can lead to the misplacement of pedicle screws. Recently, a novel intraoperative CT navigation system, NextAR, has been developed. It uses a small infrared camera mounted on surgical instruments within the surgical field. NextAR navigation can minimize the problem of infrared interference and be expected to improve the accuracy of pedicle screw placement. Methods: This study investigated the accuracy of pedicle screw insertion under NextAR navigation in spinal fusion surgery for lumbar degenerative diseases. The accuracy of pedicle screw placement was evaluated in 15 consecutive patients using a CT grading scale. Results: Screw perforation occurred in only 1 of the total 70 screws (1.4%). Specifically, there was one grade 1 perforation within 2 mm, but no perforations larger than 2 mm. There were no reoperations or neurological complications due to screw misplacement. Conclusions: NextAR navigation can provide high accuracy for pedicle screw insertion and help ensure safe spinal fusion surgery for lumbar degenerative diseases.
Prediction of Intracranial Pressure in Patients with an Aneurysmal Subarachnoid Hemorrhage Using Optic Nerve Sheath Diameter via Explainable Predictive Modeling
Authors: Kim Kwang Hyeon , Kang Hyung Koo , Koo Hae-Won
Published: April 2024

Background: The objective of this investigation was to formulate a model for predicting intracranial pressure (ICP) by utilizing optic nerve sheath diameter (ONSD) during endovascular treatment for an aneurysmal subarachnoid hemorrhage (aSAH), incorporating explainable predictive modeling. Methods: ONSD measurements were conducted using a handheld ultrasonography device during the course of endovascular treatment (n = 126, mean age 58.82 ± 14.86 years, and female ratio 67.46%). The optimal ONSD threshold associated with an increased ICP was determined. Additionally, the association between ONSD and ICP was validated through the application of a linear regression machine learning model. The correlation between ICP and various factors was explored through the modeling. Results: With an ICP threshold set at 20 cmH2O, 82 patients manifested an increased ICP, with a corresponding ONSD of 0.545 ± 0.08 cm. Similarly, with an ICP threshold set at 25 cmH2O, 44 patients demonstrated an increased ICP, with a cutoff ONSD of 0.553 cm. Conclusions: We revealed a robust correlation between ICP and ONSD. ONSD exhibited a significant association and demonstrated potential as a predictor of ICP in patients with an ICP ≥ 25 cmH2O. The findings suggest its potential as a valuable index in clinical practice, proposing a reference value of ONSD for increased ICP in the institution.
Interstitial Cells of Cajal and P2X3 Receptors at Ureteropelvic Junction Obstruction and Their Relationship with Pain Response
Authors: Borselle Dominika , Kaczorowski Maciej , Gogolok Bartosz , Patkowski Dariusz , Polok Marcin , Hałoń Agnieszka , Apoznański Wojciech
Published: April 2024

Introduction: Etiopathogenesis and the symptomatology of ureteropelvic junction obstruction (UPJO) in the pediatric population has not yet been definitely clarified, suggesting a multifactorial nature of the condition. The aim was to analyze the association between the number of Interstitial Cells of Cajal (ICCs), as well as P2X3 receptors in ureteropelvic junction (UPJ) and the pain response in pediatric patients with hydronephrosis. Methods: 50 patients with congenital hydronephrosis underwent open or laparoscopic pyeloplasty at one of two departments of pediatric surgery and urology in Poland. Patients were divided into two groups according to the pain symptoms before surgery. A total of 50 samples of UPJ were obtained intraoperatively and underwent histopathological and immunohistochemical (IHC) analysis. Quantitative assessment of ICCs was based on the number of CD117(+) cells of adequate morphology in the subepithelial layer and the muscularis propria. Expression of P2X3 receptors was evaluated as the intensity of IHC staining. Results: Patients with hydronephrosis and accompanying pain were on average 60 months older (77 vs. 17 months) than children with asymptomatic hydronephrosis (p = 0.017). Symptomatic children revealed higher numbers of ICCs in both the subepithelial layer and in the lamina muscularis propria. In particular, symptomatic patients aged 2 years or more exhibited significantly higher numbers of ICCs in the subepithelial layer. Significant differences in the distribution of ICCs between the subepithelial layer and the lamina muscularis propria were observed in both groups. Expression of P2X3 receptors was limited to the urothelium and the muscle layer and correlated between these structures. There was no relationship between pain response and the expression of P2X3 receptors. Conclusions: ICCs and P2X3 receptors may participate in the pathogenesis of UPJO and in the modulation of pain response to a dilatation of the pyelocaliceal system. Explanation of the role of ICCs and P2X3 receptors in propagation of ureteral peristaltic wave and the modulation of pain stimuli requires further studies.
Stability Analysis in a Direct-Current Shipboard Power System with Parallel Permanent Magnet Synchronous Generators and Supercapacitor Integration
Authors: Yun Qinsheng , Wang Xiangjun , Wang Shenghan , Zhuang Wei , Zhu Wanlu
Published: April 2024

This paper investigates the small-signal stability of a DC shipboard power system (SPS) with the integration of a supercapacitor. As an efficient energy storage solution, supercapacitors can not only provide rapid energy response to sudden power demand spikes, effectively mitigating load fluctuations, but also enhance the system’s resilience to disturbances. In the context of the parallel operation of two Permanent Magnet Synchronous Generators (PMSGs), the inclusion of supercapacitors may alter the system’s dynamic behaviors, thereby affecting its small-signal stability. This paper develops the small-signal model of SPS and explores the small-signal model under various power distribution strategies in the parallel operation of diesel generator sets. Through the calculation of eigenvalues and influence factors, the system’s oscillation modes are analyzed, and key parameters affecting the stability of the DC distribution system are identified. Furthermore, this paper meticulously examines the specific impacts of electrical and control parameter variations on the system’s small-signal stability. Simulation experiments validate the accuracy of the small-signal stability analysis after supercapacitor integration into SPS.
Development of SCAR Markers for Genetic Authentication of Metarhizium acridum
Authors: Toriello Conchita , Duarte-Escalante Esperanza , Frías-De-León María Guadalupe , Brunner-Mendoza Carolina , Navarro-Barranco Hortensia , Reyes-Montes María del Rocío
Published: April 2024

In this study, molecular typing using Randomly Amplified Polymorphic DNA (RAPD-PCR) was conducted on 16 original isolates of Metarhizium acridum obtained from locusts (Schistocerca piceifrons ssp. piceifrons.) in Mexico (MX). The analysis included reference strains of the genus Metarhizium sourced from various geographical regions. The isolates were identified by phenotypic (macro and micromorphology) and genotypic methods (RAPD-PCR and Amplified Fragment Length Polymorphisms (AFLP), through a multidimensional analysis of principal coordinates (PCoA) and a minimum spanning network (MST). Subsequently, Sequences-Characterized Amplified Region (SCAR) markers were developed for the molecular detection of M. acridum, these markers were chosen from polymorphic patterns obtained with 14 primers via RAPD-PCR. Phenotypic and genotypic characterization identified the MX isolates as M. acridum. Of all the polymorphic patterns obtained, only OPA04 and OPA05 were chosen, which presented species-specific bands for M. acridum, and further utilized to create SCAR markers through cloning and sequencing of the specific bands. The specificity of these two markers was confirmed via Southern hybridization. The SCAR markers (Ma-160OPA-05 and Ma-151OPA-04) exhibit remarkable sensitivity, detecting down to less than 0.1 ng, as well as high specificity, as evidenced by their inability to cross-amplify or generate amplification with DNAs from other strains of Metarhizium (as Metarhizium anisopliae) or different genera of entomopathogenic fungi (Cordyceps fumosorosea and Akanthomyces lecanii). These SCAR markers yield readily detectable results, showcasing high reproducibility. They serve as a valuable tool, especially in field applications.
Assessment of Relative Energy Deficiency in Sport (REDs) Risk among Adolescent Acrobatic Gymnasts
Authors: Besor Omri , Redlich Noam , Constantini Naama , Weiler-Sagie Michal , Monsonego Ornan Efrat , Lieberman Shira , Bentur Lea , Bar-Yoseph Ronen
Published: April 2024

Energy imbalance exposes athletes to relative energy deficiency in sports (REDs) syndrome. Data on energy consumption, REDs, and bone mineral density (BMD) in adolescent acrobatic gymnasts, especially in males, are scarce. Our aim was to examine the eating habits, energy balance, body composition, and BMD of these athletes. In this study, 18 healthy adolescents participating in competitive acrobatic gymnastics completed a questionnaire, underwent a dual-energy X-ray absorptiometry scan (DXA), received a food log, and had their activities monitored for 3 days. Eighteen acrobats were enrolled (mean age: 14.3 ± 1.2 years; males: 6/18). The mean total body BMD Z-score was 0.4 ± 1.0. Top-position acrobats (7/18) had significantly lower total body BMD Z-scores than base-positioned acrobats (−0.2 ± 0.3 vs. 0.8 ± 0.3, p = 0.032), though their forearms were not significantly different (0.2 ± 0.5 vs. 0.8 ± 0.7, p = 0.331). No sex differences were found for BMD Z-scores, BMI, or energy availability. The BMD parameters of the acrobats were within the normal range for a healthy pediatric population, although three had low BMDs (<−1 SD) for healthy athletes. Total body and LS BMD Z-scores were significantly lower in top-position athletes compared to base-position athletes. These findings suggest personalized (top vs. base) training programs (high-impact training) that may achieve better health outcomes.
Longterm Outcome of Therapeutic Vaccination with a Third Generation Pre-S/S HBV Vaccine (PreHevbrioR) of Chronically HBV Infected Patients
Authors: Roggendorf Hedwig , Shouval Daniel , Roggendorf Michael , Gerken Guido
Published: April 2024

Several antiviral treatment regimens for chronic hepatitis B (CHB) virus infection have been shown to be effective in suppressing viral load and reducing the risk of hepatocellular injury and its complications. It has been hypothesized that high levels of circulating HBV surface antigen(s) may lead to immune tolerance against HBV and contribute to chronic carriership. Conversely, low-level HBsAg may create a window for the reconstitution of an HBV-specific immune response through vaccination and control of infection. Previous studies in non-responders to yeast-derived HBV vaccines, using a third-generation pre-S/S vaccine, have led to up to 95% anti-HBs seroconversion. This report evaluates the long-term outcome after experimental vaccination with a pre-S/S HBV vaccine intended as a therapeutic intervention in chronic HBV carriers. Four low-level HBsAg carriers (<500 IU/mL) were vaccinated three to seven times with 20 μg PreHevbrioR. Three out of four carriers eliminated HBsAg completely and seroconverted to anti-HBs. One patient seroconverted to anti-HBs but remained with a borderline HBsAg titer (10 IU/mL). Serum anti-HBs levels following repeated vaccination varied between 27 and >1000 IU/L, respectively. Long-term observation (>6 years) showed that after discontinuing NUC treatment for at least two years, HBsAg and HBV DNA remained negative with anti-HBs positive titers ranging between 80 and >1000 IU/L. Based on our preliminary observations, there is a rationale to further evaluate the role of this vaccine as a therapeutic agent.
Damage Control Interventional Radiology in Liver Trauma: A Comprehensive Review
Authors: Corvino Fabio , Giurazza Francesco , Marra Paolo , Ierardi Anna Maria , Corvino Antonio , Basile Antonio , Galia Massimo , Inzerillo Agostino , Niola Raffaella
Published: April 2024

The liver is the second most common solid organ injured in blunt and penetrating abdominal trauma. Non-operative management (NOM) has become the standard of care for liver injuries in stable patients, where transarterial embolization (TAE) represents the main treatment, increasing success rates and avoiding invasive surgical procedures. In hemodynamically (HD) unstable patients, operative management (OM) is the standard of care. To date, there are no consensus guidelines about the endovascular treatment of patients with HD instability or in ones that responded to initial infusion therapy. A review of the literature was performed for published papers addressing the outcome of using TAE as the primary treatment for HD unstable/transient responder trauma liver patients with hemorrhagic vascular lesions, both as a single treatment and in combination with surgical treatment, focusing additionally on the different definitions used in the literature of unstable and transient responder patients. Our review demonstrated a good outcome in HD unstable/transient responder liver trauma patients treated with TAE but there still remains much debate about the definition of unstable and transient responder patients.
Joint Expedition: Exploring the Intersection of Digital Health and AI in Precision Medicine with Team Integration
Authors: Giansanti Daniele
Published: April 2024

Precision medicine stands as a transformative force in the orbit of healthcare, fundamentally reshaping traditional approaches by customizing therapeutic interventions to align with the distinctive attributes of individual patients [...]
Strategic Deviation and Corporate Tax Avoidance: A Risk Management Perspective
Authors: Habib Ahsan , Ranasinghe Dinithi , Perera Ahesha
Published: April 2024

We examine the association between strategic deviation—defined as the deviation of firms’ resource allocation from that of industry peers—and corporate tax avoidance. By combining the agency perspective with the risk aspect, we argue that managers of firms with high strategic deviation avoid tax compared with those of firms with low strategic deviation. High-strategic-deviant firms who avoid tax are likely to face the risk of compromising firm value. Based on a large sample of 40,168 US firm-year observations for the period 1987–2020, we find evidence supporting our hypothesis. A series of robustness tests validates our main finding. We further provide evidence to suggest that the positive association between strategic deviation and tax avoidance is stronger for deviant firms with high financial constraints, low institutional ownership, firms operating in more competitive markets, and procuring higher auditor provided tax services from incumbent auditors. Importantly, we show that the capital market penalises tax avoidance strategies undertaken by the deviant firms.
Early Detection of Hearing Loss among the Elderly
Authors: Ferrán Sol , Manrique-Huarte Raquel , Lima Janaina P. , Rodríguez-Zanetti Carla , Calavia Diego , Andrade Constanza Jimena , Terrasa David , Huarte Alicia , Manrique Manuel
Published: April 2024

Background: Age-related hearing loss (ARHL) is a complex communication disorder that affects the cochlea and central auditory pathway. The goal of this study is to characterize this type of hearing loss and to identify non-invasive, inexpensive, and quick tests to detect ARHL among elderly adults, seeking to preserve quality of life and reduce the burden on healthcare systems. Methods: An observational, prospective study is conducted with >55-year-old subjects divided into the following groups: normal range (Group A), detected but not treated (Group B), and detected and treated (Group C). During follow-up, Speech Spatial Qualities (SSQ12), and Hearing Handicap Inventory in the Elderly Screening test (HHIE-S) questionnaires were assessed, along with hearing levels (hearing thresholds at 4 kHz were studied in more depth), and a series of tests and questionnaires to assess balance, cognitive level, level of dependence, and depression. Results: A total of 710 patients were included in this study. The duration of hearing loss (11.8 yr. in Group B and 21.0 yr. in Group C) and average time-to-treatment for Group C (14.1 yr.) are both protracted. Both of the used questionnaires show statistically significant differences among the groups, revealing greater handicaps for Group C. Audiometry performed at 4 kHz shows how hearing loss progresses with age, finding differences between men and women. There is a correlation between time-to-treatment in Group C and the cognitive test DSST (−0.26; p = 0.003). Conclusions: HHIE-S, SSQ12, and 4 kHz audiometry are sensitive and feasible tests to implement in screening programs.