bluuebunny/crossref_metadata_2025 huggingface dataset:
Neonates and Infants with Left Heart Obstruction and Borderline Left Ventricle Undergoing Biventricular Repair: What Do We Know about Long-Term Outcomes? A Critical Review
Authors: Cantinotti Massimiliano , Jani Vivek , Kutty Shelby , Marchese Pietro , Franchi Eliana , Pizzuto Alessandra , Viacava Cecilia , Assanta Nadia , Santoro Giuseppe , Giordano Raffaele
Published: January 2024

Background: The decision to perform biventricular repair (BVR) in neonates and infants presenting with either single or multiple left ventricle outflow obstructions (LVOTOs) and a borderline left ventricle (BLV) is subject to extensive discussion, and limited information is known regarding the long-term outcomes. As a result, the objective of this study is to critically assess and summarize the available data regarding the prognosis of neonates and infants with LVOTO and BLV who underwent BVR. Methods: In February 2023, we conducted a review study with three different medical search engines (the National Library of Medicine, Science Direct, and Cochrane Library) for Medical Subject Headings and free text terms including “congenital heart disease”, “outcome”, and “borderline left ventricle”. The search was refined by adding keywords for “Shone’s complex”, “complex LVOT obstruction”, “hypoplastic left heart syndrome/complex”, and “critical aortic stenosis”. Results: Out of a total of 51 studies, 15 studies were included in the final analysis. The authors utilized heterogeneous definitions to characterize BLV, resulting in considerable variation in inclusion criteria among studies. Three distinct categories of studies were identified, encompassing those specifically designed to evaluate BLV, those focused on Shone’s complex, and finally those on aortic stenosis. Despite the challenges associated with comparing data originating from slightly different cardiac defects and from different eras, our results indicate a favorable survival rate and clinical outcome following BVR. However, the incidence of reintervention remains high, and concerns persist regarding residual pulmonary hypertension, which has been inadequately investigated. Conclusions: The available data concerning neonates and infants with LVOTO and BLV who undergo BVR are inadequate and fragmented. Consequently, large-scale studies are necessary to fully ascertain the long-term outcome of these complex defects.
Applicability and Validity of Second Victim Assessment Instruments among General Practitioners and Healthcare Assistants (SEVID-IX Study)
Authors: Bushuven Stefan , Trifunovic-Koenig Milena , Bunz Maxie , Weinmann-Linne Patrick , Klemm Victoria , Strametz Reinhard , Müller Beate Sigrid
Published: January 2024

Background: The second victim phenomenon and moral injury are acknowledged entities of psychological harm for healthcare providers. Both pose risks to patients, healthcare workers, and medical institutions, leading to further adverse events, economic burden, and dysfunctionality. Preceding studies in Germany and Austria showed a prevalence of second victim phenomena exceeding 53 percent among physicians, nurses, emergency physicians, and pediatricians. Using two German instruments for assessing moral injury and second victim phenomena, this study aimed to evaluate their feasibility for general practitioners and healthcare assistants. Methods: We conducted a nationwide anonymous online survey in Germany among general practitioners and healthcare assistants utilizing the SeViD (Second Victims in Deutschland) questionnaire, the German version of the Second Victim Experience and Support Tool Revised Version (G-SVESTR), and the German version of the Moral Injury Symptom and Support Scale for Health Professionals (G-MISS-HP). Results: Out of 108 participants, 67 completed the survey. In G-SVESTR, the collegial support items exhibited lower internal consistency than in prior studies, while all other scales showed good-quality properties. Personality traits, especially neuroticism, negatively correlated to age, seem to play a significant role in symptom count and warrant further evaluation. Multiple linear regression indicated that neuroticism, agreeableness, G-SVESTR, and G-MISS-HP were significant predictors of symptom count. Furthermore, moral injury partially mediated the relationship between second victim experience and symptom count. Discussion: The results demonstrate the feasible use of the questionnaires, except for collegial support. With respect to selection bias and the cross-sectional design of the study, moral injury may be subsequent to the second victim phenomenon, strongly influencing symptom count in retrospect. This aspect should be thoroughly evaluated in future studies.
Long-Term Follow-Up of HRQoL up to Six Years after Outpatient Phase-II Cardiac Rehabilitation
Authors: Auschra Bianca , Euler Sebastian , Zehnder Yara , Fuentes Artiles Rubén , Niederseer David , Zuccarella-Hackl Claudia , von Känel Roland , Jellestad Lena
Published: January 2024

Background: Low health-related quality of life (HRQoL) is associated with adverse cardiovascular outcomes in coronary heart disease (CHD) patients. Cardiac rehabilitation (CR) improves HRQoL; however, evidence on long-term HRQoL changes after CR, and their predictors, is missing. Methods: A total of 153 patients with complete HRQoL data in the short-form (SF)-36 Health Survey at CR entry, discharge and follow-up were included. Using linear mixed-effects regression models for repeated time measurements, we examined predictors of follow-up HRQoL, including age and clinical characteristics. Results: Both physical (t = −5.66, p < 0.001) and mental (t = −2.06, p = 0.040) HRQoL improved significantly from CR entry to discharge, with improvements remaining stable over a mean follow-up of four years (range 2.4–6.1). Better functional capacity (6MWT) at CR entry predicted better physical HRQoL (t = 5.50, p < 0.001) and, with a trend, better mental HRQoL (t = 1.92, p = 0.056) at follow-up. A psychiatric diagnosis at CR entry predicted better mental HRQoL at follow-up (t = 3.85, p < 0.001). Conclusions: Improvements in HRQoL during CR remain stable during long-term follow-up. Levels of functional capacity appear to be relevant to both physical and mental HRQoL at follow-up.
Pear Rootstock Effects on Seasonal Colonization Patterns of Pear Decline Phytoplasma
Authors: Kaviani Mina , Goodwin Paul H. , Hunter David M.
Published: January 2024

Pear decline (PD) phytoplasma populations were examined over one year in non-symptomatic pear trees with HW620 scions grafted onto three different rootstocks: OH×F87 (PD resistant), OH×F69 (PD susceptible), and Bartlett (PD susceptible). For all three rootstocks, populations were at a maximum during late summer for leaves and shoots, and reached their minimum in mid-winter for shoots and early spring for leaves. In contrast, roots exhibited maximum populations in mid-winter and minimum populations in mid-spring. For all tissue types, PD populations were consistently lowest in trees grafted onto OH×F87 rootstocks, intermediate in those on OH×F69, and highest on Bartlett rootstocks, demonstrating that the type of rootstock significantly impacts PD populations. While OH×F87 rootstocks had the lowest populations, they can still contain relatively high PD populations, particularly during periods with maximum populations. Future research could explore the development of even higher levels of PD resistance in pear rootstocks to reduce PD populations in both the rootstock and scion.
Implications of Vegetal Protein Hydrolysates for Improving Nitrogen Use Efficiency in Leafy Vegetables
Authors: Ciriello Michele , Campana Emanuela , De Pascale Stefania , Rouphael Youssef
Published: January 2024

Climate change and the degradation of ecosystems is an urgent issue to which the agricultural sector contributes through the overuse of productive inputs such as chemical fertilizers. A disproportionate use of nitrogenous fertilizers combined with low efficiency inevitably results in worsening environmental problems (greenhouse gas emissions, soil degradation, water eutrophication, and groundwater pollution). Nevertheless, increasing population growth puts additional pressure on the already struggling agricultural world. Awareness of these problems has pushed the world of research towards the development of more sustainable but equally efficient strategies in terms of production. The use of biostimulant substances and/or micro-organisms promoting yield, resilience to abiotic stresses in plants, and increasing the functional quality of products have been indicated as a valid strategy to improve the sustainability of agricultural practices. In modern horticulture, the use of vegetable–protein hydrolysates (V-PHs) is gaining more and more interest. These biostimulants could influence plants directly by stimulating carbon and nitrogen metabolism and interfering with hormonal activity, but also indirectly as V-PHs could improve nutrient availability in plant growth substrates and increase nutrient uptake and utilization efficiency. By exploiting this aspect, it would be possible to reduce the use of chemical fertilizers without affecting potential yields. After a brief introduction to the issues related to the intensive use of nitrogen fertilizers, this review focuses on the use of V-PHs as a strategy to increase nitrogen use efficiency (NUE). Starting with their heterogeneous origins and compositions, their effects on nitrogen metabolism, as well as the physiological and biochemical processes involved in these products, this review concludes with an in-depth discussion of the effects of V-PHs on major leafy vegetables.
Correction: Vicencio et al. Transcriptional Signatures and Network-Based Approaches Identified Master Regulators Transcription Factors Involved in Experimental Periodontitis Pathogenesis. Int. J. Mol. Sci. 2023, 24, 14835
Authors: Vicencio Emiliano , Nuñez-Belmar Josefa , Cardenas Juan P. , Cortés Bastian I. , Martin Alberto J. M. , Maracaja-Coutinho Vinicius , Rojas Adolfo , Cafferata Emilio A. , González-Osuna Luis , Vernal Rolando , Cortez Cristian
Published: January 2024

In the original publication [...]
CB2 Cannabinoid Receptor as a Potential Target in Myocardial Infarction: Exploration of Molecular Pathogenesis and Therapeutic Strategies
Authors: More Sagar A. , Deore Rucha S. , Pawar Harshal D. , Sharma Charu , Nakhate Kartik T. , Rathod Sumit S. , Ojha Shreesh , Goyal Sameer N.
Published: January 2024

The lipid endocannabinoid system has recently emerged as a novel therapeutic target for several inflammatory and tissue-damaging diseases, including those affecting the cardiovascular system. The primary targets of cannabinoids are cannabinoid type 1 (CB1) and 2 (CB2) receptors. The CB2 receptor is expressed in the cardiomyocytes. While the pathological changes in the myocardium upregulate the CB2 receptor, genetic deletion of the receptor aggravates the changes. The CB2 receptor plays a crucial role in attenuating the advancement of myocardial infarction (MI)-associated pathological changes in the myocardium. Activation of CB2 receptors exerts cardioprotection in MI via numerous molecular pathways. For instance, delta-9-tetrahydrocannabinol attenuated the progression of MI via modulation of the CB2 receptor-dependent anti-inflammatory mechanisms, including suppression of pro-inflammatory cytokines like IL-6, TNF-α, and IL-1β. Through similar mechanisms, natural and synthetic CB2 receptor ligands repair myocardial tissue damage. This review aims to offer an in-depth discussion on the ameliorative potential of CB2 receptors in myocardial injuries induced by a variety of pathogenic mechanisms. Further, the modulation of autophagy, TGF-β/Smad3 signaling, MPTP opening, and ROS production are discussed. The molecular correlation of CB2 receptors with cardiac injury markers, such as troponin I, LDH1, and CK-MB, is explored. Special attention has been paid to novel insights into the potential therapeutic implications of CB2 receptor activation in MI.
De Novo Assembly of the Genome of the Sea Urchin Paracentrotus lividus (Lamarck 1816)
Authors: Costantini Maria , Esposito Roberta , Ruocco Nadia , Caramiello Davide , Cordella Angela , Ventola Giovanna Maria , Zupo Valerio
Published: January 2024

The Mediterranean purple sea urchin Paracentrotus lividus (Lamarck 1816) is a remarkable model system for molecular, evolutionary and cell biology studies, particularly in the field of developmental biology. We sequenced the genome, performed a de novo assembly, and analysed the assembly content. The genome of P. lividus was sequenced using Illumina NextSeq 500 System (Illumina) in a 2 × 150 paired-end format. More than 30,000 open reading frames (ORFs), (more than 8000 are unique), were identified and analysed to provide molecular tools accessible for the scientific community. In particular, several genes involved in complex innate immune responses, oxidative metabolism, signal transduction, and kinome, as well as genes regulating the membrane receptors, were identified in the P. lividus genome. In this way, the employment of the Mediterranean sea urchin for investigations and comparative analyses was empowered, leading to the explanation of cis-regulatory networks and their evolution in a key developmental model occupying an important evolutionary position with respect to vertebrates and humans.
Retinal Alterations Predict Early Prodromal Signs of Neurodegenerative Disease
Authors: Casciano Fabio , Zauli Enrico , Celeghini Claudio , Caruso Lorenzo , Gonelli Arianna , Zauli Giorgio , Pignatelli Angela
Published: January 2024

Neurodegenerative diseases are an increasingly common group of diseases that occur late in life with a significant impact on personal, family, and economic life. Among these, Alzheimer’s disease (AD) and Parkinson’s disease (PD) are the major disorders that lead to mild to severe cognitive and physical impairment and dementia. Interestingly, those diseases may show onset of prodromal symptoms early after middle age. Commonly, the evaluation of these neurodegenerative diseases is based on the detection of biomarkers, where functional and structural magnetic resonance imaging (MRI) have shown a central role in revealing early or prodromal phases, although it can be expensive, time-consuming, and not always available. The aforementioned diseases have a common impact on the visual system due to the pathophysiological mechanisms shared between the eye and the brain. In Parkinson’s disease, α-synuclein deposition in the retinal cells, as well as in dopaminergic neurons of the substantia nigra, alters the visual cortex and retinal function, resulting in modifications to the visual field. Similarly, the visual cortex is modified by the neurofibrillary tangles and neuritic amyloid β plaques typically seen in the Alzheimer’s disease brain, and this may reflect the accumulation of these biomarkers in the retina during the early stages of the disease, as seen in postmortem retinas of AD patients. In this light, the ophthalmic evaluation of retinal neurodegeneration could become a cost-effective method for the early diagnosis of those diseases, overcoming the limitations of functional and structural imaging of the deep brain. This analysis is commonly used in ophthalmic practice, and interest in it has risen in recent years. This review will discuss the relationship between Alzheimer’s disease and Parkinson’s disease with retinal degeneration, highlighting how retinal analysis may represent a noninvasive and straightforward method for the early diagnosis of these neurodegenerative diseases.
BP-M345 as a Basis for the Discovery of New Diarylpentanoids with Promising Antimitotic Activity
Authors: Moreira Joana , Silva Patrícia M. A. , Castro Eliseba , Saraiva Lucília , Pinto Madalena , Bousbaa Hassan , Cidade Honorina
Published: January 2024

Recently, the diarylpentanoid BP-M345 (5) has been identified as a potent in vitro growth inhibitor of cancer cells, with a GI50 value between 0.17 and 0.45 µM, showing low toxicity in non-tumor cells. BP-M345 (5) promotes mitotic arrest by interfering with mitotic spindle assembly, leading to apoptotic cell death. Following on from our previous work, we designed and synthesized a library of BP-M345 (5) analogs and evaluated the cell growth inhibitory activity of three human cancer cell lines within this library in order to perform structure–activity relationship (SAR) studies and to obtain compounds with improved antimitotic effects. Four compounds (7, 9, 13, and 16) were active, and the growth inhibition effects of compounds 7, 13, and 16 were associated with a pronounced arrest in mitosis. These compounds exhibited a similar or even higher mitotic index than BP-M345 (5), with compound 13 displaying the highest antimitotic activity, associated with the interference with mitotic spindle dynamics, inducing spindle collapse and, consequently, prolonged mitotic arrest, culminating in massive cancer cell death by apoptosis.
Associations between Cerebrovascular Function and the Expression of Genes Related to Endothelial Function in Hormonal Migraine
Authors: Dzator Jemima S. A. , Smith Robert A. , Coupland Kirsten G. , Howe Peter R. C. , Griffiths Lyn R.
Published: January 2024

There is evidence to suggest that hormonal migraine is associated with altered cerebrovascular function. We aimed to investigate whether the expression of genes related to endothelial function in venous blood (1) might influence cerebrovascular function, (2) differs between hormonal migraineur and non-migraineur women, and (3) changes following resveratrol supplementation. This study utilised data obtained from 87 women (59 hormonal migraineurs and 28 controls) where RNA from venous blood was used to quantify gene expression and transcranial Doppler ultrasound was used to evaluate cerebrovascular function. Spearman’s correlation analyses were performed between gene expression, cerebrovascular function, and migraine-related disability. We compared the expression of genes associated with endothelial function between migraineurs and non-migraineurs, and between resveratrol and placebo. The expression of several genes related to endothelial function was associated with alterations in cerebrovascular function. Notably, the expression of CALCA was associated with increased neurovascular coupling capacity (p = 0.013), and both CALCA (p = 0.035) and VEGF (p = 0.014) expression were associated with increased cerebral blood flow velocity in the overall study population. Additionally, VCAM1 expression correlated with decreased pulsatility index (a measure of cerebral arterial stiffness) (p = 0.009) and headache impact test-6 scores (p = 0.007) in the migraineurs. No significant differences in gene expression were observed between migraineurs and controls, or between placebo and resveratrol treatments in migraineurs. Thus, altering the expression of genes related to endothelial function may improve cerebrovascular function and decrease migraine-related disability.
Effects of a Combination of Polynucleotide and Hyaluronic Acid for Treating Osteoarthritis
Authors: Choi Seung Hee , Kim Hyun Chul , Jang Seul Gi , Lee Yeon Jae , Heo Jun Young , Kweon Gi Ryang , Ryu Min Jeong
Published: January 2024

Knee osteoarthritis (OA), an age-related degenerative disease characterized by severe pain and disability, is treated using polynucleotides (PNs) and hyaluronic acid (HA). The intra-articular (IA) injection of HA has been studied extensively in both animal models and in humans; however, the efficacy and mechanisms of action remain unclear. In addition, there has been a paucity of research regarding the use of PN alone or in combination with HA in OA. To investigate the effect of the combined injection of PN and HA in vivo, pathological and behavioral changes were assessed in an OA model. Anterior cruciate ligament transection and medial meniscectomy were performed in Sprague-Dawley rats to create the OA animal model. The locomotor activity improved following PNHA injection, while the OARSI grade improved in the medial tibia and femur. In mild OA, TNFα levels decreased histologically in the PN, HA, and PNHA groups but only the PNHA group showed behavioral improvement in terms of distance. In conclusion, PNHA exhibited anti-inflammatory effects during OA progression and improved locomotor activity regardless of the OARSI grade.
Aphidius colemani Behavior Changes Depending on Volatile Organic Compounds Emitted by Plants Infected with Viruses with Different Modes of Transmission
Authors: Clemente-Orta Gemma , Cabello Ángel , Garzo Elisa , Moreno Aranzazu , Fereres Alberto
Published: January 2024

Natural enemies are an additional component that may interact directly with the plant–virus–vector association, affecting viral dispersion. In our study, we conducted olfactometry assays to explore how single and mixed infections with CMV or/and CABYV modify the attractiveness of A. colemani to aphid-free and aphid-infested melon plants using two melon genotypes. Subsequently, we investigated the influence of CABYV-infected plants infested by A. gossypii on the parasitism rate and emergence of A. colemani in a dual-choice assay under greenhouse conditions. Our study demonstrates that males showed no preference for either infected or non-infected plants. Female parasitoids exhibit a preference for volatiles emitted by CMV and mixed-infected melon plants over clean air but not over mock-inoculated plants, suggesting a response influenced by plant genotype. Female parasitoid responses to CABYV and its interactions with aphids revealed a preference for mock-inoculated plants over CABYV-infected plants and a parasitism rate slightly higher (7.12%) on non-infected plants. Our study revealed that (1) parasitoids may reject olfactory cues from CABYV-infected plants, potentially interfering with the plant’s “cry for help” response; (2) in the case of CMV, whether in single or mixed infections, non-infected plants are as attractive as infected ones to parasitoids. Our findings suggest that persistent viruses manipulate aphid parasitoid behavior to their advantage, promoting virus disease in melon crops.
Accuracy and Completeness of ChatGPT-Generated Information on Interceptive Orthodontics: A Multicenter Collaborative Study
Authors: Hatia Arjeta , Doldo Tiziana , Parrini Stefano , Chisci Elettra , Cipriani Linda , Montagna Livia , Lagana Giuseppina , Guenza Guia , Agosta Edoardo , Vinjolli Franceska , Hoxha Meladiona , D’Amelio Claudio , Favaretto Nicolò , Chisci Glauco
Published: January 2024

Background: this study aims to investigate the accuracy and completeness of ChatGPT in answering questions and solving clinical scenarios of interceptive orthodontics. Materials and Methods: ten specialized orthodontists from ten Italian postgraduate orthodontics schools developed 21 clinical open-ended questions encompassing all of the subspecialities of interceptive orthodontics and 7 comprehensive clinical cases. Questions and scenarios were inputted into ChatGPT4, and the resulting answers were evaluated by the researchers using predefined accuracy (range 1–6) and completeness (range 1–3) Likert scales. Results: For the open-ended questions, the overall median score was 4.9/6 for the accuracy and 2.4/3 for completeness. In addition, the reviewers rated the accuracy of open-ended answers as entirely correct (score 6 on Likert scale) in 40.5% of cases and completeness as entirely correct (score 3 n Likert scale) in 50.5% of cases. As for the clinical cases, the overall median score was 4.9/6 for accuracy and 2.5/3 for completeness. Overall, the reviewers rated the accuracy of clinical case answers as entirely correct in 46% of cases and the completeness of clinical case answers as entirely correct in 54.3% of cases. Conclusions: The results showed a high level of accuracy and completeness in AI responses and a great ability to solve difficult clinical cases, but the answers were not 100% accurate and complete. ChatGPT is not yet sophisticated enough to replace the intellectual work of human beings.
Prognostic Implications of Type 2 Diabetes Mellitus in Heart Failure with Mildly Reduced Ejection Fraction
Authors: Schupp Tobias , Abumayyaleh Mohammad , Weidner Kathrin , Lau Felix , Reinhardt Marielen , Abel Noah , Schmitt Alexander , Forner Jan , Ayasse Niklas , Bertsch Thomas , Akin Muharrem , Akin Ibrahim , Behnes Michael
Published: January 2024

Background: Data regarding the characterization and outcomes of diabetics with heart failure with a mildly reduced ejection fraction (HFmrEF) is scarce. This study investigates the prevalence and prognostic impact of type 2 diabetes in patients with HFmrEF. Methods: Consecutive patients with HFmrEF (i.e., left ventricular ejection fraction 41–49% and signs and/or symptoms of HF) were retrospectively included at one institution from 2016 to 2022. Patients with type 2 diabetes (dia-betics) were compared to patients without (i.e., non-diabetics). The primary endpoint was all-cause mortality at 30 months. Statistical analyses included Kaplan–Meier, multivariable Cox regression analyses and propensity score matching. Results: A total of 2169 patients with HFmrEF were included. The overall prevalence of type 2 diabetes was 36%. Diabetics had an increased risk of 30-months all-cause mortality (35.8% vs. 28.6%; HR = 1.273; 95% CI 1.092–1.483; p = 0.002), which was confirmed after multivariable adjustment (HR = 1.234; 95% CI 1.030–1.479; p = 0.022) and propensity score matching (HR = 1.265; 95% CI 1.018–1.572; p = 0.034). Diabetics had a higher risk of HF-related rehospitalization (17.8% vs. 10.7%; HR = 1.714; 95% CI 1.355–2.169; p = 0.001). Finally, the risk of all-cause mortality was increased in diabetics treated with insulin (40.7% vs. 33.1%; log-rank p = 0.029), whereas other anti-diabetic pharmacotherapies had no prognostic impact in HFmrEF. Conclusions: Type 2 diabetes is common and independently associated with adverse long-term prognosis in patients with HFmrEF.
Comorbidities in COPD: Current and Future Treatment Challenges
Authors: Mariniello Domenica Francesca , D’Agnano Vito , Cennamo Donatella , Conte Stefano , Quarcio Gianluca , Notizia Luca , Pagliaro Raffaella , Schiattarella Angela , Salvi Rosario , Bianco Andrea , Perrotta Fabio
Published: January 2024

Chronic obstructive pulmonary disease (COPD) is a heterogeneous lung condition, primarily characterized by the presence of a limited airflow, due to abnormalities of the airways and/or alveoli, that often coexists with other chronic diseases such as lung cancer, cardiovascular diseases, and metabolic disorders. Comorbidities are known to pose a challenge in the assessment and effective management of COPD and are also acknowledged to have an important health and economic burden. Local and systemic inflammation have been proposed as having a potential role in explaining the association between COPD and these comorbidities. Considering that the number of patients with COPD is expected to rise, understanding the mechanisms linking COPD with its comorbidities may help to identify new targets for therapeutic purposes based on multi-dimensional assessments.
Preventing and Managing Iatrogenic Dry Eye Disease during the Entire Surgical Pathway: A Study Focusing on Patients Undergoing Cataract Surgery
Authors: Giannaccare Giuseppe , Barabino Stefano , Di Zazzo Antonio , Villani Edoardo
Published: January 2024

Patient expectations for cataract surgery are continuously increasing, and dry eye disease (DED) represents a major cause of patient dissatisfaction in eye surgery. The present opinion paper aims to provide useful insights to improve the entire pathway of a patient undergoing cataract surgery, from the preoperative setting to the postoperative one. The available evidence from main clinical trials published on this topic is presented in association with experience-based points of view by the authors. Ocular surface disease (OSD) is common in patients presenting for cataract surgery, and more than half of these patients have DED and meibomian gland dysfunction (MGD), even in the absence of symptoms. Therefore, there is a need to encourage preoperative assessments for the risk of DED development or worsening in all patients as a routine approach to cataract surgery. New all-in-one diagnostic machines allow for fast and noninvasive screening of the ocular surface status. Once a preoperative diagnosis of DED/OSD is reached, ocular surface optimization should be obtained before surgery. In the case of unresolved OSD, the decision to delay surgery should be considered. The surgical procedure can be optimized by avoiding large incisions, limiting microscope light intensity and exposure, and avoiding an aspirating speculum or preserved eye drops. Postoperatively, the continued avoidance of preserved agents is advisable, as well as a limited exposure to epitheliotoxic antibiotics and nonsteroidal anti-inflammatory drugs. Short-term, preservative-free, soft corticosteroids may be useful for patients with extensive or persistent inflammation.
Eosinophilic Patterns in Patients with Seasonal Allergy Affected by Bronchial Asthma and Rhinitis/Rhinosinusitis: Efficacy of Benralizumab in Patients with the Persistent Pattern
Authors: D’Aiuto Valentina , Mormile Ilaria , Granata Francescopaolo , Romano Antonio , Della Casa Francesca , D’Onofrio Caterina , Marzio Valentina , Mignogna Gabriele , Califano Luigi , de Paulis Amato , Rossi Francesca Wanda
Published: January 2024

Background: Eosinophilia can be influenced by multiple factors. This study aims to set a protocol for monitoring blood absolute eosinophil count (AEC) in patients with seasonal allergy affected by bronchial asthma (BA), allergic rhinitis (AR), or chronic rhinosinusitis with or without nasal polyposis (CRSw/sNP). Methods: We planned a total of four annual blood samples to measure AEC in- and out-seasonal pollen exposure (i.e., one measurement every three months for one year). Results: We identified two distinct groups of patients (non-eosinophilic and eosinophilic). Patients in the eosinophilic group presented with four different patterns (episodic, transient, floating, and persistent). Most patients with episodic, transient, and floating patterns were affected by mild allergy and the increase in eosinophils was related to allergen exposure. In contrast, patients with the persistent pattern mostly presented with more severe allergy (i.e., severe BA and relapsing CRSwNP) and the eosinophilia was unrelated to allergen exposure. The subgroup of patients with severe BA, relapsing CRSwNP, and persistent eosinophilc pattern were treated with benralizumab, which induced a noteworthy improvement in both severe BA and CRSwNP. Conclusions: Multiple AEC measurements in patients with seasonal allergy can better reflect patient’s eosinophilic status and help define the relationship of AEC enhancement with allergen exposure.
Intramedullary Nail vs. Plate Fixation for Pathological Humeral Shaft Fracture: An Updated Narrative Review and Meta-Analysis of Surgery-Related Factors
Authors: Chen Bing-Kuan , Tai Ting-Han , Lin Shu-Hsuan , Chen Kuan-Hao , Huang Yu-Min , Chen Chih-Yu
Published: January 2024

(1) Background: Pathological humeral shaft fracture (PHSF) is a frequently observed clinical manifestation in the later stages of tumor metastasis. Surgical interventions are typically recommended to alleviate pain and restore functionality. Intramedullary nail fixation (INF) or plate fixation (PF) is currently recommended for the treatment of PHSF. However, there is still no standard for optimal surgical treatment. Thus, we conducted a meta-analysis comparing the clinical outcomes of INF with PF for PHSF treatment. (2) Methods: We conducted searches in databases, such as Scopus, EMBASE, and PubMed, for studies published prior to May 2023. In total, nine studies with 485 patients were reviewed. (3) Results: There were no significant differences noted in the incidence of fixation failure, local recurrence, wound complication or overall complication. However, the INF group demonstrated a significantly lower incidence of postoperative radial nerve palsy than the PF group (OR, 5.246; 95% CI, 1.548–17.774; p = 0.008). A subgroup analysis indicated that there were no statistically significant differences in fixation failure or local recurrence among subgroups categorized by the design of intramedullary nail. (4) Conclusions: Considering the short life expectancy of end-stage patients, the choice of surgical method depends on the patient’s individual condition, fracture and lesion patterns, the surgeon’s experience, and comprehensive discussion between the surgeon and patient.
Comparison of the Analgesic Efficacy between Levobupivacaine 0.25% and Ropivacaine 0.375% for PENG (Pericapsular Nerve Group) Block in the Context of Hip Fracture Surgery of Elderly Patients: A Single-Center, Randomized, and Controlled Clinical Trial
Authors: Salgado-García Daniel , Díaz-Álvarez Agustín , González-Rodríguez José Luis , López-Iglesias María Rocío , Sánchez-López Eduardo , Sánchez-Ledesma Manuel Jesús , Martínez-Trufero María Isabel
Published: January 2024

Previous studies have compared levobupivacaine versus ropivacaine in various peripheral nerve blocks in terms of block duration, quality of analgesia, and onset time, but this has not occurred in the PENG block. Here, a single-center, randomized, and controlled clinical trial is presented. One hundred and twenty patients older than 65 years suffering from hip fractures and surgically treated at our institution under spinal anesthesia were eligible for participation; of them, one hundred and eight were analyzed. Patients were randomized to receive ultrasound-guided PENG blocks using 20 mL of either 0.25% levobupivacaine or 0.375% ropivacaine (both of which are equipotent concentrations). The primary endpoint was to compare the analgesic duration (time to first rescue) and analgesic quality (pain scores using the VAS, PAINAD, and AlgoPlus scales) between the groups. Secondary endpoints included comparing the onset time, describing the need for and type of rescue analgesics, and possible associated adverse effects. There were no statistically significant differences in analgesic duration between levobupivacaine (median 861.0, IQR 960) and ropivacaine (median 1205.0, IQR 1379; p = 0.069). Likewise, the quality of analgesia and onset time were comparable among the groups. A small number of patients required opioids as rescue analgesics (4.6%). The possible associated adverse effects included postoperative infection (11.1%) and delirium (2.8%).
e14a2 Transcript Favors Treatment-Free Remission in Chronic Myeloid Leukemia When Associated with Longer Treatment with Tyrosine Kinase Inhibitors and Sustained Deep Molecular Response
Authors: Marcé Sílvia , Méndez Aleix , Xicoy Blanca , Estrada Natalia , Cabezón Marta , Sturla Antonella Luciana , García Miriam Ratia , Angona Anna , Amat Paula , Escribano Serrat Silvia , Scalzulli Emilia , Morgades Mireia , Senín Alicia , Hernández-Boluda Juan Carlos , Ferrer-Marín Francisca , Anguita Eduardo , Cortés Montserrat , Plensa Esther , Breccia Massimo , García-Gutierrez Valentín , Zamora Lurdes
Published: January 2024

e13a2 and e14a2 are the most frequent transcript types of the BCR::ABL1 fusion gene in chronic myeloid leukemia (CML). The current goal with tyrosine kinase inhibitors (TKI) is to achieve sustained deep molecular response (DMR) in order to discontinue TKI treatment and remain in the so-called treatment-free remission (TFR) phase, but biological factors associated with these goals are not well established. This study aimed to determine the effect of transcript type on TFR in patients receiving frontline treatment with imatinib (IM) or second-generation TKI (2G-TKI). Patients treated at least 119 months with IM presented less post-discontinuation relapse than those that discontinued IM before 119 months (p = 0.005). In addition, cases with the e14a2 transcript type treated at least 119 months with IM presented a better TFR (p = 0.024). On the other hand, the type of transcript did not affect the cytogenetic or molecular response in 2G-TKI treated patients; however, the use of 2G-TKI may be associated with higher and earlier DMR in patients with the e14a2 transcript.
Vagus Nerve Stimulation Therapy for Drug-Resistant Epilepsy in Children—A Literature Review
Authors: Fukuda Mitsumasa , Matsuo Takeshi , Fujimoto So , Kashii Hirofumi , Hoshino Ai , Ishiyama Akihiko , Kumada Satoko
Published: January 2024

Vagus nerve stimulation (VNS) is a palliative treatment for drug-resistant epilepsy (DRE) that has been in use for over two decades. VNS suppresses epileptic seizures, prevents emotional disorders, and improves cognitive function and sleep quality, a parallel effect associated with the control of epileptic seizures. The seizure suppression rate with VNS increases monthly to annually, and the incidence of side effects reduces over time. This method is effective in treating DRE in children as well as adults, such as epilepsy associated with tuberous sclerosis, Dravet syndrome, and Lennox–Gastaut syndrome. In children, it has been reported that seizures decreased by >70% approximately 8 years after initiating VNS, and the 50% responder rate was reported to be approximately 70%. VNS regulates stimulation and has multiple useful systems, including self-seizure suppression using magnets, additional stimulation using an automatic seizure detection system, different stimulation settings for day and night, and an automatic stimulation adjustment system that reduces hospital visits. VNS suppresses seizures and has beneficial behavioral effects in children with DRE. This review describes the VNS system, the mechanism of the therapeutic effect, the specific stimulation adjustment method, antiepileptic effects, and other clinical effects in patients with childhood DRE.
Analgesic Efficacy of Oxycodone in Postoperative Dressings after Surgical Treatment of Burn Wounds: A Randomised Controlled Trial
Authors: Kowalski Grzegorz , Leppert Wojciech , Domagalska Małgorzata , Grochowicka Monika , Teżyk Artur , Słowiński Krzysztof , Bienert Agnieszka , Szkutnik-Fiedler Danuta , Wieczorowska-Tobis Katarzyna
Published: January 2024

Introduction: This study aimed to assess the analgesic efficacy of oxycodone at doses of 10 mg and 20 mg in dressings after surgery of burn wounds. Material and Methods: Twenty adult patients who underwent surgical treatment of third-degree burn wounds under general anaesthesia were included. Burn wounds were treated with dressings, to which oxycodone was added at 20 mg in Group 1 and 10 mg in Group 2. After the surgery, plasma oxycodone and noroxycodone concentrations were assayed, and pain intensity was assessed with Numerical Rating Scale (NRS). Results: In Group 1, no patient reported pain; in Group 2, four patients reported pain. The pain intensity, according to NRS, was 1–8. Plasma concentration of oxycodone in the blood serum was in the range of 1.24–3.15 ng/mL and 1.09–1.28 ng/mL in Group 1 and Group 2, respectively. Noroxycodone was not detected in the plasma. Adverse effects were not observed in any of the treated patients. Conclusions: Oxycodone in dressings provides patients with adequate and safe analgesia.
Left Atrial Appendage Occlusion and Post-procedural Antithrombotic Management
Authors: Kramer Anders , Patti Giuseppe , Nielsen-Kudsk Jens Erik , Berti Sergio , Korsholm Kasper
Published: January 2024

Left atrial appendage occlusion (LAAO) is an established alternative to oral anticoagulation for stroke prevention in atrial fibrillation. Antithrombotic therapy is used in the post-procedural period to prevent device-related thrombosis (DRT). The risk of DRT is considered highest in the first 45–90 days after device implantation, based on animal studies of the device healing process. Clinically applied antithrombotic regimens vary greatly across studies, continents, and centers. This article gives an overview of the evidence behind current antithrombotic regimens, ongoing randomized trials, and future post-procedural management.
Benefits of Robot-Assisted Upper-Limb Rehabilitation from the Subacute Stage after a Stroke of Varying Severity: A Multicenter Randomized Controlled Trial
Authors: Ahn So Young , Bok Soo-Kyung , Lee Ji Young , Ryoo Hyeon Woo , Lee Hoo Young , Park Hye Jung , Oh Hyun Mi , Kim Tae-Woo
Published: January 2024

Background: The aim of this study was to compare the clinical effectiveness of robot-assisted therapy with that of conventional occupational therapy according to the onset and severity of stroke. Methods: In this multicenter randomized controlled trial, stroke patients were randomized (1:1) to receive robot-assisted therapy or conventional occupational therapy. The robot-assisted training group received 30 min of robot-assisted therapy twice and 30 min of conventional occupational therapy daily, while the conventional therapy group received 90 min of occupational therapy. Therapy was conducted 5 days/week for 4 weeks. The primary outcome was the Wolf Motor Function Test (WMFT) score after 4 and 8 weeks of therapy. Results: Overall, 113 and 115 patients received robot-assisted and conventional therapy, respectively. The WMFT score after robot-assisted therapy was not significantly better than that after conventional therapy, but there were significant improvements in the Motricity Index (trunk) and the Fugl–Meyer Assessment. After robot-assisted therapy, wrist strength significantly improved in the subacute or moderate-severity group of stroke patients. Conclusions: Robot-assisted therapy improved the upper-limb functions and activities of daily living (ADL) performance as much as conventional occupational therapy. In particular, it showed signs of more therapeutic effectiveness in the subacute stage or moderate-severity group.
Nanocomposite Material Based on Polyvinyl Alcohol Modified with Carbon Nanotubes: Mechanism of Formation and Electronic Energy Structure
Authors: Elbakyan Lusine , Zaporotskova Irina , Hayrapetyan David
Published: January 2024

The physical chemistry of surface phenomena in polymers is an important issue when studying the interaction of polymers with solid surfaces. This is due to the fact that most of the modern polymer materials are heterogeneous systems with highly developed phase separation surfaces. An example of such materials can be reinforced plastic, filled thermoplastics, reinforced rubber, paint coatings, etc. Polymer adsorption at the boundary of the phase separation process in solids plays an important role in the reinforcing effect of fillers, adhesion, gluing and obtaining composite materials with high strength properties. Compositions based on polyvinyl alcohol (PVA) modified with carbon nanotubes (CNTs) can be used as an interesting and informative system for studying the structure and properties of polymer nanocomposites, especially in a highly oriented state. PVA has one of the simplest chemical structure among the polymers, containing a functional (hydroxyl) group capable of participating in interphase interactions. In turn, carbon nanotubes with unique strength properties are currently products of industrial production, which makes it possible to control and modify their properties. To prove the possibility of creating new composite materials with improved strength characteristics, the mechanisms of interaction between PVA and CNTs are studied by modeling the adsorption processes of a polymer fragment on the outer surface of single-layer carbon nanotubes of different chirality, performed within the framework of the modern DFT calculation method. The main adsorption characteristics of the process and the features of the electron energy structure of the resulting composite systems are determined.
Multifunctional ZnO@DOX/ICG-LMHP Nanoparticles for Synergistic Multimodal Antitumor Activity
Authors: Li Zhuoyue , Wang Jingru , Liu Junwei , Yu Jianming , Wang Jingwen , Wang Hui , Wei Qingchao , Liu Man , Xu Meiqi , Feng Zhenhan , Zhong Ting , Zhang Xuan
Published: January 2024

Multifunctional nanoparticles are of significant importance for synergistic multimodal antitumor activity. Herein, zinc oxide (ZnO) was used as pH-sensitive nanoparticles for loading the chemotherapy agent doxorubicin (DOX) and the photosensitizer agent indocyanine green (ICG), and biocompatible low-molecular-weight heparin (LMHP) was used as the gatekeepers for synergistic photothermal therapy/photodynamic therapy/chemotherapy/immunotherapy. ZnO was decomposed into cytotoxic Zn2+ ions, leading to a tumor-specific release of ICG and DOX. ZnO simultaneously produced oxygen (O2) and reactive oxygen species (ROS) for photodynamic therapy (PDT). The released ICG under laser irradiation produced ROS for PDT and raised the tumor temperature for photothermal therapy (PTT). The released DOX directly caused tumor cell death for chemotherapy. Both DOX and ICG also induced immunogenic cell death (ICD) for immunotherapy. The in vivo and in vitro results presented a superior inhibition of tumor progression, metastasis and recurrence. Therefore, this study could provide an efficient approach for designing multifunctional nanoparticles for synergistic multimodal antitumor therapy.
Design of Laser Activated Antimicrobial Porous Tricalcium Phosphate-Hydroxyapatite Scaffolds for Orthopedic Applications
Authors: Filipov Emil , Yildiz Ridvan , Dikovska Anna , Sotelo Lamborghini , Soma Tharun , Avdeev Georgi , Terziyska Penka , Christiansen Silke , Leriche Anne , Fernandes Maria Helena , Daskalova Albena
Published: January 2024

The field of bone tissue engineering is steadily being improved by novel experimental approaches. Nevertheless, microbial adhesion after scaffold implantation remains a limitation that could lead to the impairment of the regeneration process, or scaffold rejection. The present study introduces a methodology that employs laser-based strategies for the development of antimicrobial interfaces on tricalcium phosphate–hydroxyapatite (TCP-HA) scaffolds. The outer surfaces of the ceramic scaffolds with inner porosity were structured using a femtosecond laser (λ = 800 nm; τ = 70 fs) for developing micropatterns and altering local surface roughness. The pulsed laser deposition of ZnO was used for the subsequent functionalization of both laser-structured and unmodified surfaces. The impact of the fs irradiation was investigated by Raman spectroscopy and X-ray diffraction. The effects of the ZnO-layered ceramic surfaces on initial bacterial adherence were assessed by culturing Staphylococcus aureus on both functionalized and non-functionalized scaffolds. Bacterial metabolic activity and morphology were monitored via the Resazurin assay and microscopic approaches. The presence of ZnO evidently decreased the metabolic activity of bacteria and led to impaired cell morphology. The results from this study have led to the conclusion that the combination of fs laser-structured surface topography and ZnO could yield a potential antimicrobial interface for implants in bone tissue engineering.
Advancements and Challenges in Additively Manufactured Functionally Graded Materials: A Comprehensive Review
Authors: Alkunte Suhas , Fidan Ismail , Naikwadi Vivekanand , Gudavasov Shamil , Ali Mohammad Alshaikh , Mahmudov Mushfig , Hasanov Seymur , Cheepu Muralimohan
Published: January 2024

This paper thoroughly examines the advancements and challenges in the field of additively manufactured Functionally Graded Materials (FGMs). It delves into conceptual approaches for FGM design, various manufacturing techniques, and the materials employed in their fabrication using additive manufacturing (AM) technologies. This paper explores the applications of FGMs in diverse fields, including structural engineering, automotive, biomedical engineering, soft robotics, electronics, 4D printing, and metamaterials. Critical issues and challenges associated with FGMs are meticulously analyzed, addressing concerns related to production and performance. Moreover, this paper forecasts future trends in FGM development, highlighting potential impacts on diverse industries. The concluding section summarizes key findings, emphasizing the significance of FGMs in the context of AM technologies. This review provides valuable insights to researchers, practitioners, and stakeholders, enhancing their understanding of FGMs and their role in the evolving landscape of AM.