bluuebunny/crossref_metadata_2025 huggingface dataset:
Factor XI in Carriers of Antiphospholipid Antibodies: Elevated Levels Associated with Symptomatic Thrombotic Cases, While Low Levels Linked to Asymptomatic Cases
Authors: Pagán-Escribano Javier , Corral Javier , Miñano Antonia , Padilla José , Roldán Vanessa , Hernández-Vidal María Julia , Lozano Jesús , de la Morena-Barrio Isabel , Vicente Vicente , Lozano María Luisa , Herranz María Teresa , de la Morena-Barrio María Eugenia
Published: November 2023

Antiphospholipid syndrome (APS) is a thromboinflammatory disorder caused by circulating antiphospholipid autoantibodies (aPL) and characterized by an increased risk of thrombotic events. The pathogenic mechanisms of these antibodies are complex and not fully understood, but disturbances in coagulation and fibrinolysis have been proposed to contribute to the thrombophilic state. This study aims to evaluate the role of an emerging hemostatic molecule, FXI, in the thrombotic risk of patients with aPL. Cross-sectional and observational study of 194 consecutive and unrelated cases with aPL recruited in a single center: 82 asymptomatic (AaPL) and 112 with primary antiphospholipid syndrome (APS). Clinical and epidemiological variables were collected. The profile of aPL was determined. Plasma FXI was evaluated by Western blotting and two coagulation assays (FXI:C). In cases with low FXI, molecular analysis of the F11 gene was performed. FXI:C levels were significantly higher in patients with APS than in patients with AaPL (122.8 ± 33.4 vs. 104.5 ± 27.5; p < 0.001). Multivariate analysis showed a significant association between symptomatic patients with aPL (APS) and high FXI (>150%) (OR = 11.57; 95% CI: 1.47–90.96; p = 0.020). In contrast, low FXI (<70%), mostly caused by inhibitors, was less frequent in the group of patients with APS compared to AaPL (OR = 0.17; 95%CI: 0.36–0.86; p = 0.032). This study suggests that FXI levels may play a causal role in the prothrombotic state induced by aPLs and holds the promise of complementary treatments in APS patients by targeting FXI.
Tumor Regression upon Intratumoral and Subcutaneous Dosing of the STING Agonist ALG-031048 in Mouse Efficacy Models
Authors: Jekle Andreas , Thatikonda Santosh Kumar , Jaisinghani Ruchika , Ren Suping , Kinkade April , Stevens Sarah K. , Stoycheva Antitsa , Rajwanshi Vivek K. , Williams Caroline , Deval Jerome , Mukherjee Sucheta , Zhang Qingling , Chanda Sushmita , Smith David B. , Blatt Lawrence M. , Symons Julian A. , Gonzalvez Francois , Beigelman Leonid
Published: November 2023

Stimulator of interferon genes (STING) agonists have shown potent anti-tumor efficacy in various mouse tumor models and have the potential to overcome resistance to immune checkpoint inhibitors (ICI) by linking the innate and acquired immune systems. First-generation STING agonists are administered intratumorally; however, a systemic delivery route would greatly expand the clinical use of STING agonists. Biochemical and cell-based experiments, as well as syngeneic mouse efficacy models, were used to demonstrate the anti-tumoral activity of ALG-031048, a novel STING agonist. In vitro, ALG-031048 is highly stable in plasma and liver microsomes and is resistant to degradation via phosphodiesterases. The high stability in biological matrices translated to good cellular potency in a HEK 293 STING R232 reporter assay, efficient activation and maturation of primary human dendritic cells and monocytes, as well as long-lasting, antigen-specific anti-tumor activity in up to 90% of animals in the CT26 mouse colon carcinoma model. Significant reductions in tumor growth were observed in two syngeneic mouse tumor models following subcutaneous administration. Combinations of ALG-031048 and ICIs further enhanced the in vivo anti-tumor activity. This initial demonstration of anti-tumor activity after systemic administration of ALG-031048 warrants further investigation, while the combination of systemically administered ALG-031048 with ICIs offers an attractive approach to overcome key limitations of ICIs in the clinic.
Steady and Unsteady Numerical Characterization of the Secondary Flow Structures of a Highly Loaded Low-Pressure Compressor Stage
Authors: Toracchio Riccardo , Fontaneto Fabrizio , Hillewaert Koen
Published: November 2023

This paper presents the numerical characterization of a highly loaded compressor by means of 3D unsteady RANS simulations. The focus is on critical flow structures and their evolution at different operating points of the machine. First, the numerical setup and mesh quality are presented to support the reliability of the provided results. The comparison against experiments is then described for this purpose. Later, a full description of the unsteady behavior of the machine is provided, giving special attention to the two regions where the most critical features are expected: the rotor hub wall and the casing. Rotor–stator interactions are then investigated and the role of the inlet guide vane (IGV) is finally discussed. Results are analyzed at design and near-stall conditions, with a focus on the behavior close to the stability limit at 100% speed.
Naturally Occurring Vegetation Connectivity Facilitates Ant-Mediated Coffee Berry Borer Removal
Authors: Cowal Sanya , Morris Jonathan R. , Jiménez-Soto Estelí , Philpott Stacy M.
Published: November 2023

Vegetation connectivity is an essential aspect of the habitat complexity that impacts species interactions at local scales. However, agricultural intensification reduces connectivity in agroforestry systems, including coffee agroecosystems, which may hinder the movement of natural enemies and reduce the ecosystem services that they provide. Ants play an important role in regulating the coffee berry borer (CBB), which is the most damaging coffee pest. For arboreal ant communities, the connections between trees are important structures that facilitate ant mobility, resource recruitment, foraging success, and pest control ability. To better understand how connectivity impacts arboreal ants in coffee agroecosystems, we conducted an experiment to assess the impact of artificial (string) and naturally occurring vegetation (vines, leaves, branches) connectivity on Azteca sericeasur behavior on coffee plants. We compared ant activity, resource recruitment, and CBB removal rates across three connectivity treatments connecting coffee plants to A. sericeasur nest trees: vegetation connectivity, string, and control (not connected) treatments. We found higher rates of ant activity, resource recruitment, and CBB removal on plants with naturally occurring vegetation connections to A. sericeasur nest trees. Artificial connectivity (string) increased the rates of resource recruitment and CBB removal but to a lesser extent than vegetation connectivity. Moreover, vegetation connectivity buffered reductions in ant activity with distance from the ant nest tree. These results reinforce how habitat complexity in the form of vegetation connectivity impacts interspecific interactions at the local scale. Our results also suggest that leaving some degree of vegetation connectivity between coffee plants and shade trees can promote ant-mediated biological pest control in coffee systems.
Differential Effects of Two Tomato Begomoviruses on the Life History and Feeding Preference of Bemisia tabaci
Authors: Wu Hsin-Yu , Li Wei-Hua , Weng Sung-Hsia , Tsai Wen-Shi , Tsai Chi-Wei
Published: November 2023

Tomato yellow leaf curl disease, caused by a group of closely related tomato yellow leaf curl viruses, is a major threat to tomato cultivation worldwide. These viruses are primarily transmitted by the sweet potato whitefly (Bemisia tabaci) in a persistent-circulative manner, wherein the virus circulates in the body of B. tabaci and infects its tissues. The complex relationship between viruses and whiteflies significantly influences virus transmission, with studies showing varying effects of the former on the life history and feeding preference of the latter. Whether these effects are direct or indirect, and whether they are negative, neutral, or positive, appears to depend on the specific interactions between virus and whitefly species. The tomato yellow leaf curl Thailand virus (TYLCTHV) and the tomato leaf curl Taiwan virus (ToLCTV) are two prevalent begomoviruses in fields in Taiwan. This study examined the direct and indirect effects of TYLCTHV and ToLCTV on the life history traits (longevity, fecundity, nymph survival, and nymph developmental time) and feeding preference of B. tabaci Middle East–Asia Minor 1 (MEAM1). The results revealed that TYLCTHV had no effects on these life history traits or the feeding preference of MEAM1 whiteflies. Although ToLCTV did not directly affect the longevity and fecundity of MEAM1 whiteflies, their fecundity and the nymph developmental time were negatively affected by feeding on ToLCTV-infected plants. In addition, ToLCTV infection also altered the feeding preference of MEAM1 whiteflies. The different effects of virus infection may contribute to the lower prevalence of ToLCTV compared to TYLCTHV in fields in Taiwan.
Complex Effects of a Land-Use Gradient on Pollinators and Natural Enemies: Natural Habitats Mitigate the Effects of Aphid Infestation on Pollination Services
Authors: Shapira Tal , Roth Tohar , Bar Adi , Coll Moshe , Mandelik Yael
Published: November 2023

Pollinators and natural enemies are essential ecosystem service providers influenced by land-use and by interactions between them. However, the understanding of the combined impacts of these factors on pollinator and natural enemy activities and their ultimate effects on plant productivity remains limited. We investigated the effects of local and landscape vegetation characteristics and the presence of herbivorous pests on pollination and biological control services and their combined influence on phytometer seed set. The study was conducted in a Mediterranean agro-ecosystem, encompassing ten shrubland plots spanning a land-use gradient. Within each plot, we placed caged and uncaged potted phytometer plants that were either aphid-infested or aphid-free. We quantified insect flower visitation, aphid predation and parasitism rates, and fruit and seed set. We found scale-dependent responses of pollinators and natural enemies to land-use characteristics. Flower species richness had a positive impact on aphid parasitism rates but a negative effect on pollinator activity. Notably, we found a more pronounced positive effect of natural areas on pollinator activity in aphid-infested compared to aphid-free plants, indicating a potentially critical role of natural habitats in mitigating the adverse effects of aphid infestation on pollination services. These results highlight the complex and interactive effects of land-use on pollinators and natural enemies, with significant implications for plant productivity.
Surgical Strategy for Sternal Closure in Patients with Surgical Myocardial Revascularization Using Mammary Arteries
Authors: Robu Mircea , Rădulescu Bogdan , Margarint Irina , Știru Ovidiu , Antoniac Iulian , Gheorghiță Daniela , Voica Cristian , Nica Claudia , Cacoveanu Mihai , Iliuță Luminița , Iliescu Vlad Anton , Moldovan Horațiu
Published: November 2023

Background: Coronary artery bypass grafting has evolved from all venous grafts to bilateral mammary artery (BIMA) grafting. This was possible due to the long-term patency of the left and right internal mammary demonstrated in angiography studies compared to venous grafts. However, despite higher survival rates when using bilateral mammary arteries, multiple studies report a higher rate of surgical site infections, most notably deep sternal wound infections, a so-called “never event”. Methods: We designed a prospective study between 1 January 2022 and 31 December 2022 and included all patients proposed for total arterial myocardial revascularization in order to investigate the rate of surgical site infections (SSI). Chest closure in all patients was performed using a three-step protocol. The first step refers to sternal closure. If the patient’s BMI is below 35 kg/m2, sternal closure is achieved using the “butterfly” technique with standard steel wires. If the patient’s BMI exceeds 35 kg/m2, we use nitinol clips or hybrid wire cable ties according to the surgeon’s preference for sternal closure. The main advantages of these systems are a larger implant-to-bone contact with a reduced risk of bone fracture. The second step refers to presternal fat closure with two resorbable monofilament sutures in a way that the edges of the skin perfectly align at the end. The third step is skin closure combined with negative pressure wound therapy. Results: This system was applied to 217 patients. A total of 197 patients had bilateral mammary artery grafts. We report only 13 (5.9%) superficial SSI and only one (0.46%) deep SSI. The preoperative risk of major wound infection was 3.9 +/− 2.7. Bilateral mammary artery grafting was not associated with surgical site infection in a univariate analysis. Conclusions: We believe this strategy of sternal wound closure can reduce the incidence of deep surgical site infection when two mammary arteries are used in coronary artery bypass surgery.
Epidemiology and Reporting Characteristics of Systematic Reviews in Orthopedic Journals: A Meta-Epidemiological Study
Authors: Yamamoto Norio , Taito Shunsuke , Miura Takanori , Ariie Takashi , Tomita Yosuke , Ogihara Hirofumi , Shiratsuchi Daijo , Yorifuji Takashi , Tsujimoto Yasushi
Published: November 2023

Systematic reviews (SRs) with complete reporting or rigorous methods can lead to less biased recommendations and decisions. A comprehensive analysis of the epidemiological and reporting characteristics of SRs in orthopedics is lacking. We evaluated 360 SRs, including 165 and 195 published in orthopedic journals in 2012 and 2022. According to the established reporting guidelines, we examined these SRs for key epidemiological characteristics, including focus areas, type of meta-analysis (MA), and reporting characteristics. Most SRs (71%) were therapy-related, with a significant proportion originating from authors in the USA, UK, and China. Pairwise MA was performed on half of the SRs. The proportion of protocol registrations improved by 2022 but remained low (33%). Despite a formal declaration of adherence to the reporting guidelines (68%), they were often not used and reported enough. Only 10% of the studies used full search strategies, including trial registries. Publication bias assessments, subgroup analyses, and sensitivity analyses were not even planned. The risk of bias assessment improved in 2022; however, the certainty of the evidence remained largely unassessed (8%). The use and reporting of standard methods in orthopedic SRs have remained suboptimal. Thus, authors, peer reviewers, journal editors, and readers should criticize the results more.
Pharmacoepidemiology: An Overview
Authors: Sabaté Mònica , Montané Eva
Published: November 2023

The aims of this review are to provide a comprehensive overview of the definition and scope of pharmacoepidemiology, to summarize the study designs and methodologies used in the field, to discuss the future trends in the field and new methodologies to address bias and confounding, and finally to give some recommendations to clinicians interested in pharmacoepidemiologic research. Because drug efficacy and safety from randomized clinical trials do not reflect the real-world situation, pharmacoepidemiological studies on drug safety monitoring and drug effectiveness in large numbers of people are needed by healthcare professionals and regulatory institutions. We aim to highlight the importance of pharmacoepidemiologic research in informing evidence-based medicine and public health policy. The development of new designs and methodologies for the generation of valid evidence, as well as new initiatives to provide guidance and recommendations on how to incorporate real-world evidence into the drug development process, are reported on. In addition, we have touched on the implication of artificial intelligence in the management of real-world data. This overview aims to summarize all important aspects to consider when conducting or interpreting a pharmacoepidemiologic study.
Structural and Functional Retinal Changes in Patients with Mild Cognitive Impairment with and without Diabetes
Authors: Santos-Ortega Álvaro , Alba-Linero Carmen , Urbinati Facundo , Rocha-de-Lossada Carlos , Orti Rafael , Reyes-Bueno José Antonio , Garzón-Maldonado Francisco Javier , Serrano Vicente , de Rojas-Leal Carmen , de la Cruz-Cosme Carlos , España-Contreras Manuela , Rodríguez-Calvo-de-Mora Marina , García-Casares Natalia
Published: November 2023

Our objective is to analyze retinal changes using optical coherence tomography angiography (OCT-A) in patients with mild cognitive impairment (MCI) to characterize structural and vascular alterations. This cross-sectional study involved 117 eyes: 39 eyes from patients with MCI plus diabetes (DM-MCI), 39 eyes from patients with MCI but no diabetes (MCI); and 39 healthy control eyes (C). All patients underwent a visual acuity measurement, a structural OCT, an OCT-A, and a neuropsychological examination. Our study showed a thinning of retinal nerve fiber layer thickness (RNFL) and a decrease in macular thickness when comparing the MCI-DM group to the C group (p = 0.008 and p = 0.016, respectively). In addition, an increase in arteriolar thickness (p = 0.016), a reduction in superficial capillary plexus density (p = 0.002), and a decrease in ganglion cell thickness (p = 0.027) were found when comparing the MCI-DM group with the MCI group. Diabetes may exacerbate retinal vascular changes when combined with mild cognitive impairment.
Predicting the Outcome of Patients with Aneurysmal Subarachnoid Hemorrhage: A Machine-Learning-Guided Scorecard
Authors: Zhang Yi , Zeng Hanhai , Zhou Hang , Li Jingbo , Wang Tingting , Guo Yinghan , Cai Lingxin , Hu Junwen , Zhang Xiaotong , Chen Gao
Published: November 2023

Aneurysmal subarachnoid hemorrhage (aSAH) frequently causes long-term disability, but predicting outcomes remains challenging. Routine parameters such as demographics, admission status, CT findings, and blood tests can be used to predict aSAH outcomes. The aim of this study was to compare the performance of traditional logistic regression with several machine learning algorithms using readily available indicators and to generate a practical prognostic scorecard based on machine learning. Eighteen routinely available indicators were collected as outcome predictors for individuals with aSAH. Logistic regression (LR), random forest (RF), support vector machines (SVMs), and fully connected neural networks (FCNNs) were compared. A scorecard system was established based on predictor weights. The results show that machine learning models and a scorecard achieved 0.75~0.8 area under the curve (AUC) predicting aSAH outcomes (LR 0.739, RF 0.749, SVM 0.762~0.793, scorecard 0.794). FCNNs performed best (~0.95) but lacked interpretability. The scorecard model used only five factors, generating a clinically useful tool with a total cutoff score of ≥5, indicating poor prognosis. We developed and validated machine learning models proven to predict outcomes more accurately in individuals with aSAH. The parameters found to be the most strongly predictive of outcomes were NLR, lymphocyte count, monocyte count, hypertension status, and SEBES. The scorecard system provides a simplified means of applying predictive analytics at the bedside using a few key indicators.
Fibrosing Progressive Interstitial Lung Disease in Rheumatoid Arthritis: A Multicentre Italian Study
Authors: Sebastiani Marco , Venerito Vincenzo , Laurino Elenia , Gentileschi Stefano , Atzeni Fabiola , Canofari Claudia , Andrisani Dario , Cassone Giulia , Lavista Marlea , D’Alessandro Francesco , Vacchi Caterina , Scardapane Arnaldo , Frediani Bruno , Cazzato Massimiliano , Salvarani Carlo , Iannone Florenzo , Manfredi Andreina
Published: November 2023

Background: The INBUILD study demonstrated the efficacy of nintedanib in the treatment of progressive fibrosing interstitial lung disease different to idiopathic pulmonary fibrosis, including rheumatoid arthritis (RA)-related ILD. Nevertheless, the prevalence of RA-ILD patients that may potentially benefit from nintedanib remains unknown. Objectives and methods: The aim of the present multicentre study was to investigate the prevalence and possible associated factors of fibrosing progressive patterns in a cross-sectional cohort of RA-ILD patients. Results: One hundred and thirty-four RA-ILD patients with a diagnosis of RA-ILD, who were confirmed at high-resolution computed tomography and with a follow-up of at least 24 months, were enrolled. The patients were defined as having a progressive fibrosing ILD in case of a relative decline in forced vital capacity > 10% predicted and/or an increased extent of fibrotic changes on chest imaging in a 24-month period. Respiratory symptoms were excluded to reduce possible bias due to the retrospective interpretation of cough and dyspnea. According to radiologic features, ILD was classified as usual interstitial pneumonia (UIP) in 50.7% of patients, nonspecific interstitial pneumonia in 19.4%, and other patterns in 29.8%. Globally, a fibrosing progressive pattern was recorded in 36.6% of patients (48.5% of patients with a fibrosing pattern) with a significant association to the UIP pattern. Conclusion: We observed that more than a third of RA-ILD patients showed a fibrosing progressive pattern and might benefit from antifibrotic treatment. This study shows some limitations, such as the retrospective design. The exclusion of respiratory symptoms’ evaluation might underestimate the prevalence of progressive lung disease but increases the value of results.
Endocarditis after Transcatheter Aortic Valve Replacement
Authors: Braghieri Lorenzo , Kaur Simrat , Black Christopher K. , Cremer Paul C. , Unai Shinya , Kapadia Samir R. , Mentias Amgad
Published: November 2023

Transcatheter aortic valve replacement (TAVR) use is gaining momentum as the mainstay for the treatment of aortic stenosis compared to surgical aortic valve replacement (SAVR). Unfortunately, TAVR-related infective endocarditis (TAVR-IE) is expected to be detected more and more as a result of the ever-expanding indications in younger patients. Given the overall poor prognosis of TAVR-IE, it is imperative that clinicians familiarize themselves with common presentations, major risk factors, diagnostic pitfalls, therapeutic approaches, and the prevention of TAVR-IE. Herein, we review all of the above in detail with the most updated available literature.
Protein Biomarkers Shared by Multiple Neurodegenerative Diseases Are Calmodulin-Binding Proteins Offering Novel and Potentially Universal Therapeutic Targets
Authors: O’Day Danton H.
Published: November 2023

Seven major neurodegenerative diseases and their variants share many overlapping biomarkers that are calmodulin-binding proteins: Alzheimer’s disease (AD), amyotrophic lateral sclerosis (ALS), frontotemporal lobar dementia (FTD), Huntington’s disease (HD), Lewy body disease (LBD), multiple sclerosis (MS), and Parkinson’s disease (PD). Calcium dysregulation is an early and persistent event in each of these diseases, with calmodulin serving as an initial and primary target of increased cytosolic calcium. Considering the central role of calcium dysregulation and its downstream impact on calcium signaling, calmodulin has gained interest as a major regulator of neurodegenerative events. Here, we show that calmodulin serves a critical role in neurodegenerative diseases via binding to and regulating an abundance of biomarkers, many of which are involved in multiple neurodegenerative diseases. Of special interest are the shared functions of calmodulin in the generation of protein biomarker aggregates in AD, HD, LBD, and PD, where calmodulin not only binds to amyloid beta, pTau, alpha-synuclein, and mutant huntingtin but also, via its regulation of transglutaminase 2, converts them into toxic protein aggregates. It is suggested that several calmodulin binding proteins could immediately serve as primary drug targets, while combinations of calmodulin binding proteins could provide simultaneous insight into the onset and progression of multiple neurodegenerative diseases.
The Effect of Antidepressant Treatment on Neurocognitive Functions, Redox and Inflammatory Parameters in the Context of COVID-19
Authors: Samaryn Eliza , Galińska-Skok Beata , Nobis Aleksander , Zalewski Daniel , Maciejczyk Mateusz , Gudowska-Sawczuk Monika , Mroczko Barbara , Zalewska Anna , Waszkiewicz Napoleon
Published: November 2023

Inflammation is an important component of the etiopathology of depression that uses oxidative and nitrosative stress (O&NS) and elevated inflammatory markers. SARS-CoV-2 infection is also associated with abnormal inflammatory processes, which may impair effective treatment of depression in COVID-19 survivors. In the presented study, thirty-three hospitalized patients with major depressive disorder (MDD) were started on antidepressant treatment, and twenty-one were re-evaluated after 4–6 weeks. The control group consisted of thirty healthy volunteers. All participants underwent neuropsychiatric evaluation, biochemical blood and urine analyses. The results of the research demonstrated positive correlations of the Hamilton Depression Rating Scale (HAM-D) scores with serum catalase (CAT) and urinary S-Nitrosothiols levels, and the Beck Depression Inventory (BDI) scores with serum reduced glutathione (GSH) and superoxide dismutase (SOD) levels. Depressed patients with a history of COVID-19 prior to the treatment had higher urinary nitric oxide (NO) levels and lower serum glutathione peroxidase (GPx) levels. In the control group, COVID-19 survivors had higher levels of urinary N-formylkynurenine (NFK). Our results suggest that the antidepressant treatment has a modulating effect on O&NS, reduces depressive symptoms and improves cognitive functions The present study does not indicate that clinical response to antidepressant treatment is associated with COVID-19 history and baseline SARS-CoV-2 antibody levels. Nevertheless, further research in this area is needed to systematize antidepressant treatment in COVID-19 survivors.
Anthracycline’s Effects on Heart Rate Variability in Children with Acute Lymphoblastic Leukemia: Early Toxicity Signs—Pilot Study
Authors: Lazar Diana R. , Cainap Simona , Maniu Dana , Blag Cristina , Bota Madalina , Lazar Florin-Leontin , Achim Alexandru , Colceriu Marius C. , Zdrenghea Mihnea
Published: November 2023

Anthracycline treatments are known to cause cardiotoxic long-term side effects in cancer survivors. Recently, a decrease in heart rate variability (HRV) has been identified in these patients, signaling autonomic dysfunction and altered cardiac fitness. This study aimed at evaluating changes in HRV in children treated with anthracyclines. A total of 35 pediatric patients with acute lymphoblastic leukemia were evaluated by means of a 24 h Holter ECG, at baseline and after reaching half the total cumulative dose of doxorubicin equivalent (120 mg/m2). Parameters of HRV were assessed, as well as any arrhythmic episodes, bradycardia and tachycardia percentages. The results showed a significant decrease in both time-domain and frequency-domain HRV parameters, following anthracycline treatment. The low-frequency (LF) to high-frequency (HF) parameters’ ratio also displayed a significant difference (p = 0.035), suggestive of early cardiac autonomic dysfunction. Of note, none of the patients presented symptoms of heart disease or elevated troponins, and only two patients presented echocardiographic signs of diastolic dysfunction. The present study showed that cardiac autonomic nervous system regulation is compromised in children treated with anthracyclines even before reaching the total cumulative dose. Therefore, HRV parameters could be the first indicators of subclinical cardiac toxicity, making Holter ECG monitoring of the oncological patient a necessity.
Correction: Bocci et al. Remarkable Remission Rate and Long-Term Efficacy of Upfront Metronomic Chemotherapy in Elderly and Frail Patients, with Diffuse Large B-Cell Lymphoma. J. Clin. Med. 2022, 11, 7162
Authors: Bocci Guido , Pelliccia Sabrina , Orlandi Paola , Caridi Matteo , Banchi Marta , Musuraca Gerardo , Di Napoli Arianna , Bianchi Maria Paola , Patti Caterina , Anticoli-Borza Paola , Battistini Roberta , Casaroli Ivana , Lanzolla Tiziana , Tafuri Agostino , Cox Maria Christina
Published: November 2023

In the original publication [...]
The Impact of Head Position on Neurological and Histopathological Outcome Following Controlled Automated Reperfusion of the Whole Body (CARL) in a Pig Model
Authors: Damjanovic Domagoj , Pooth Jan-Steffen , Liu Yechi , Frensch Fabienne , Wolkewitz Martin , Haberstroh Joerg , Doostkam Soroush , Cristina Schmitz Heidi Ramona , Foerster Katharina , Taunyane Itumeleng , Neubert Tabea , Scherer Christian , Diel Patric , Benk Christoph , Beyersdorf Friedhelm , Trummer Georg
Published: November 2023

Introduction: Based on extracorporeal circulation, targeted reperfusion strategies have been developed to improve survival and neurologic recovery in refractory cardiac arrest: Controlled Automated Reperfusion of the whoLe Body (CARL). Furthermore, animal and human cadaver studies have shown beneficial effects on cerebral pressure due to head elevation during conventional cardiopulmonary resuscitation. Our aim was to evaluate the impact of head elevation on survival, neurologic recovery and histopathologic outcome in addition to CARL in an animal model. Methods: After 20 min of ventricular fibrillation, 46 domestic pigs underwent CARL, including high, pulsatile extracorporeal blood flow, pH–stat acid–base management, priming with a colloid, mannitol and citrate, targeted oxygen, carbon dioxide and blood pressure management, rapid cooling and slow rewarming. N = 25 were head-up (HUP) during CARL, and N = 21 were supine (SUP). After weaning from ECC, the pigs were extubated and followed up in the animal care facility for up to seven days. Neuronal density was evaluated in neurohistopathology. Results: More animals in the HUP group survived and achieved a favorable neurological recovery, 21/25 (84%) versus 6/21 (29%) in the SUP group. Head positioning was an independent factor in neurologically favorable survival (p < 0.00012). Neurohistopathology showed no significant structural differences between HUP and SUP. Distinct, partly transient clinical neurologic deficits were blindness and ataxia. Conclusions: Head elevation during CARL after 20 min of cardiac arrest independently improved survival and neurologic outcome in pigs. Clinical follow-up revealed transient neurologic deficits potentially attributable to functions localized in the posterior perfusion area, whereas histopathologic findings did not show corresponding differences between the groups. A possible explanation of our findings may be venous congestion and edema as modifiable contributing factors of neurologic injury following prolonged cardiac arrest.
Short-Term Evaluation of Bone–ACL–Bone Complex Allograft in ACL Reconstruction in a Rabbit Model
Authors: Liu Yulei , Havasy Janice , Green Samuel , Deng Xiang-Hua , Chen Daoyun , Piacentini Alexander , Rodeo Scott A.
Published: November 2023

The study is to evaluate incorporation of a bone-anterior cruciate ligament-bone (B-ACL-B) allograft in anterior cruciate ligament (ACL) reconstruction in a rabbit model. A total of 61 New Zealand white rabbits were used, with 23 donor rabbits for harvesting B-ACL-B allografts and 38 recipient rabbits undergoing unilateral ACL reconstruction with B-ACL-B allograft. Animals were euthanized for biomechanical testing, micro-computed tomography examination, histological analysis, multi-photon microscopy and transmission electron microscopy testing at 2, 4 and 8 weeks after surgery. Gross inspection and radiographs confirmed the intact ACL allograft in the proper anatomic position. Progressive healing occurred between the bone block and the bone tunnel as demonstrated by a gradual increase in average bone volume fraction and total mineral density at 4 and 8 weeks. Histological analysis showed new bone formation at the bone block–tunnel interface, with maintenance of the native ACL enthesis. Ultrastructural analysis demonstrated the maintenance of overall collagen matrix alignment, while there was repopulation with smaller diameter collagen fibrils. There was no significant difference between 4 and 8 weeks in mean failure force (p = 0.39) or stiffness (p = 0.15) for the B-ACL-B allografts. This study demonstrates the restoration of the normal anatomy of the ACL and progressive graft incorporation and remodeling using a B-ACL-B allograft for ACL reconstruction in the rabbit knee.
Menopause Predisposes Women to Increased Risk of Cardiovascular Disease
Authors: Kamińska Magdalena Sylwia , Schneider-Matyka Daria , Rachubińska Kamila , Panczyk Mariusz , Grochans Elżbieta , Cybulska Anna Maria
Published: November 2023

(1) Background: Menopause is an important event in women’s lives, possibly contributing to the development of CVD, which is associated with changes in the cardiovascular risk profile, markers of metabolic health, and subclinical atherosclerosis. The aim of this study was to assess the association of menopause with CVD risk factors and subclinical markers of cardiometabolic disease. (2) Methods: The study involved 235 women from the general population at different stages of menopause. The methods used in this study were: diagnostic survey, anthropometric measurement (WC, height, BMI, WHtR), blood pressure measurement, biochemical analysis of venous blood (lipid profile, glucose, insulin, HbA1c), and CVD risk assessment (ASCVD Risk Calculator, POL-SCORE, SCORE-2). (3) Results: The vast majority of respondents had low cardiovascular risk, irrespective of the scale used for measuring the risk of CVD. The age at menopause was not an independent risk factor for CVD. In Model 1, the age at menopause and the time since menopause were found to be factors that increased CVD risk (OR = 1.186 and 1.267, respectively). In Models 2 and 3, the severity of menopausal symptoms was not a risk factor for CVD. Models 3 and 4 demonstrated that women with metabolic syndrome (MetS) were at a significantly higher risk of CVD. In model 5, the odds ratio of CVD with MetS as a standalone factor was 13.812. (4) Conclusions: Menopause predisposes women to an increased risk and MetS to a significantly higher risk of CVD.
IL-6 Receptor Expression on the Surface of T Cells and Serum Soluble IL-6 Receptor Levels in Patients with Microscopic Polyangiitis and Granulomatosis with Polyangiitis
Authors: Yoon Taejun , Ahn Sung Soo , Ko Eunhee , Song Jason Jungsik , Park Yong-Beom , Lee Sang-Won
Published: November 2023

We investigated the IL-6 receptor (IL-6R) expression on the surface of T cells isolated from peripheral blood mononuclear cells (PBMCs) of microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA) patients and measured the serum soluble IL-6R (sIL-6R) levels in these patients. Sera and PBMCs were obtained from 51 patients with MPA (n = 32) and GPA (n = 19), with 25 patients having active disease (defined as a Birmingham Vasculitis Activity Score [BVAS] ≥ 5). The median age of patients was 67.0 years, and 52.9% were women. Serum IL-6 levels were significantly correlated with the BVAS (r = 0.384); however, IL-6R expression on the surface of T cells did not significantly differ based on disease activity. Meanwhile, IL-6R expression on the surface of stimulated CD4+ (median mean fluorescence intensity [MFI] 588.0 vs. 1314.8; p < 0.001), CD4+CD25+ (MFI 853.3 vs. 1527.3; p < 0.001), and CD4+CD45RO+ (MFI 679.5 vs. 1241.5; p < 0.001) T cells was significantly reduced compared with unstimulated conditions. Conversely, patients with active disease exhibited a significantly higher median serum sIL-6R level than those with inactive disease (38.1 ng/mL vs. 34.7 ng/mL; p = 0.029). These results imply that the trans-signalling IL-6 pathway may be more activated than the classical signalling pathway in patients with MPA and GPA, suggesting the therapeutic potential of targeting sIL-6R.
The Prevalence of Neck and Back Pain among Paramedics in Poland
Authors: Bryndal Aleksandra , Glowinski Sebastian , Hebel Kazimiera , Grochulska Julia , Grochulska Agnieszka
Published: November 2023

Neck Pain (NP) and low back pain (LBP) are ubiquitous musculoskeletal conditions and some of the major causes of disability worldwide. The aim of the study was to assess the incidence and risk factors of back pain among paramedics and their correlation with the nature of work, anthropometric features and the level of recreational physical activity. A group of 201 individuals (39 females (19.40%); 162 males (80.60%)), licensed to practice as paramedics in Poland completed a questionnaire containing the author’s interview as well as the Neck Disability Index (NDI) questionnaire and the Revised Oswestry Disability Index (ODI). Among the examined paramedics, 92% of the subjects reported the presence of back pain in different parts of the spine (36% C; 17% Th; and 85% LBP). The pain intensity, determined by VAS, was on average 4.26 (SD 1.77). The level of disability, assessed by NDI, was 7.67 (SD 5.73) on average, while the ODI was 7.51 (5.90). Work-related spinal strain has a major impact on the intensity and incidence of spinal pain. Spinal pain in paramedics mainly occurs in the lower back.
Dynamic CT Myocardial Perfusion: The Role of Functional Evaluation in the Diagnosis of Coronary Artery Disease
Authors: Zdanowicz Agata , Guzinski Maciej , Pula Michal , Witkowska Agnieszka , Reczuch Krzysztof
Published: November 2023

Coronary computed tomography angiography (CTA) is a widely accepted, non-invasive diagnostic modality for the evaluation of patients with suspected coronary artery disease (CAD). However, a limitation of CTA is its inability to provide information on the hemodynamic significance of the coronary lesion. The recently developed stress dynamic CT perfusion technique has emerged as a potential solution to this diagnostic challenge. Dynamic CT myocardial perfusion provides information on the hemodynamic consequences of coronary stenosis and is used to detect myocardial ischemia. The combination of stress dynamic CT myocardial perfusion with CTA provides a comprehensive assessment that integrates anatomical and functional information. CT myocardial perfusion has been validated in several clinical studies and has shown comparable accuracy to Positron Emission Tomography (PET) and stress magnetic resonance imaging (MRI) in the diagnosis of hemodynamically significant coronary stenosis and superior performance to Single Photon Emission Computed Tomography (SPECT). More importantly, CTP-derived myocardial perfusion has been shown to have a strong correlation with FFR, and the use of CTP results in a reduction of negative catheterizations. In the context of suspected stable coronary artery disease, the CT protocol with dynamic perfusion imaging combined with CTA eliminates the need for additional testing, making it a convenient “one-stop-shop” method and an effective gatekeeper to an invasive approach.
A Randomized Controlled Trial to Evaluate the Impact of an Exercise Therapy Program Based on Sports in People with Acquired Brain Injury: Discover Study Protocol
Authors: Gutiérrez-Suárez Andrea , Pérez-Rodríguez Marta , García-Hernández Juan José , Rodríguez-Romero Beatriz
Published: November 2023

Introduction: Acquired brain injury (ABI) constitutes a significant and growing global public health concern. People with ABI often face a range of physical and psychosocial challenges that span the domains of “body structure and function”, “activity”, and “participation”, as defined by the International Classification of Functioning, Disability, and Health. Multidisciplinary approaches based on exercise therapy with social leisure activities are essential to improve physical recovery and health-related quality of life after injury. Methods: Adults with ABI, aged > 18 years, in the subacute or chronic stage (within more than one month after the injury) will be recruited through a rehabilitation center. Adults will be randomized to receive either a racket sports-based exercise therapy program combined with usual care (sET) or usual care alone (UC) using a random number sequence with a 1:1 allocation ratio. sET intervention consists of an 8-week exercise therapy program focusing on different racket sports skills, 1 h in duration, 2 days/week. It will be delivered by a physiotherapist in tailored, face-to-face, group-based sessions. Primary outcomes will be the health-related quality of life (SF-36) and upper extremity motor function (Fugl-Meyer Assessment-Upper Extremity Scale). Discussion: The study proposes an intervention that combines sports-based exercise therapy with usual care. It aims to determine whether this intervention improves the health-related quality of life and upper limb motor function in adults with ABI compared with usual care alone. The results of this study may have clinical implications for the rehabilitation of this population.
MR-Guided Focused Ultrasound for Refractory Epilepsy: Where Are We Now?
Authors: Labate Angelo , Bertino Salvatore , Morabito Rosa , Smorto Chiara , Militi Annalisa , Cammaroto Simona , Anfuso Carmelo , Tomaiuolo Francesco , Tonin Paolo , Marino Silvia , Cerasa Antonio , Quartarone Angelo
Published: November 2023

Epilepsy is one of the most common neurological diseases in both adults and children. Despite improvements in medical care, 20 to 30% of patients are still resistant to the best medical treatment. The quality of life, neurologic morbidity, and even mortality of patients are significantly impacted by medically intractable epilepsy. Nowadays, conservative therapeutic approaches consist of increasing medication dosage, changing to a different anti-seizure drug as monotherapy, and combining different antiseizure drugs using an add-on strategy. However, such measures may not be sufficient to efficiently control seizure recurrence. Resective surgery, ablative procedures and non-resective neuromodulatory (deep-brain stimulation, vagus nerve stimulation) treatments are the available treatments for these kinds of patients. However, invasive procedures may involve lengthy inpatient stays for the patients, risks of long-term neurological impairment, general anesthesia, and other possible surgery-related complications (i.e., hemorrhage or infection). In the last few years, MR-guided focused ultrasound (MRgFUS) has been proposed as an emerging treatment for neurological diseases because of technological advancements and the goal of minimally invasive neurosurgery. By outlining the current knowledge obtained from both preclinical and clinical studies and discussing the technical opportunities of this therapy for particular epileptic phenotypes, in this perspective review, we explore the various mechanisms and potential applications (thermoablation, blood-brain barrier opening for drug delivery, neuromodulation) of high- and low-intensity ultrasound, highlighting possible novel strategies to treat drug-resistant epileptic patients who are not eligible or do not accept currently established surgical approaches. Taken together, the available studies support a possible role for lesional treatment over the anterior thalamus with high-intensity ultrasound and neuromodulation of the hippocampus via low-intensity ultrasound in refractory epilepsy. However, more studies, likely conceiving epilepsy as a network disorder and bridging together different scales and modalities, are required to make ultrasound delivery strategies meaningful, effective, and safe.
The Influence of Composite Luminescent Materials Based on Graphene Oxide on the Growth and Development of Solanum lycopersicum in Greenhouses
Authors: Paskhin Mark O. , Pobedonostsev Roman V. , Kazantseva Dina V. , Simakin Alexander V. , Gorudko Irina V. , Yanykin Denis V. , Gudkov Sergey V.
Published: November 2023

The effect of graphene oxide-based photoconversion covers on the growth and photosynthesis of tomatoes (Solanum lycopersicum) was investigated. Two types of photoconversion composite for covers were produced. In the first, only graphene oxide nanoparticles were used as a phosphor, and in the second, the graphene oxide nanoparticles were used jointly with europium oxide nanoparticles. The freshly prepared composites for covers had almost identical photoluminescence spectra: an intense peak in the red region and a minor peak in the blue region. It was revealed that during operation, luminescence in the red region decreased, while in the blue region it increased, probably due to the photothermal reduction of graphene oxide. It was shown that the photoconversion covers increased productivity (25%) and intensified photosynthesis (30–35%) in the tomato plants. It is suggested that the stimulation of plant growth is caused by changes in the light spectrum induced by the photoconversion covers.
Advances in Fabrication Technologies for the Development of Next-Generation Cardiovascular Stents
Authors: Das Ankita , Mehrotra Shreya , Kumar Ashok
Published: November 2023

Coronary artery disease is the most prevalent cardiovascular disease, claiming millions of lives annually around the world. The current treatment includes surgically inserting a tubular construct, called a stent, inside arteries to restore blood flow. However, due to lack of patient-specific design, the commercial products cannot be used with different vessel anatomies. In this review, we have summarized the drawbacks in existing commercial metal stents which face problems of restenosis and inflammatory responses, owing to the development of neointimal hyperplasia. Further, we have highlighted the fabrication of stents using biodegradable polymers, which can circumvent most of the existing limitations. In this regard, we elaborated on the utilization of new fabrication methodologies based on additive manufacturing such as three-dimensional printing to design patient-specific stents. Finally, we have discussed the functionalization of these stent surfaces with suitable bioactive molecules which can prove to enhance their properties in preventing thrombosis and better healing of injured blood vessel lining.