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Background and Objectives: Anterior visual pathway involvement is common in multiple sclerosis (MS) and optical coherence tomography (OCT) can be utilized to examine the integrity of the ganglion cell axons (peri-papillary retinal nerve fiber layer; pRNFL) and cell bodies (ganglion cell & inner plexiform layer; GCIPL). OCT angiography (OCTA) can be used to investigate the retinal microvasculature. In this systematic review and meta-analysis, we synthesized OCT and OCTA findings in MS., Methods: We identified studies that performed OCT and OCTA in people with MS and included data permitting at least one of the following comparisons: 1) MS optic neuritis (MS-ON) vs healthy-control (HC) eyes; 2) MS non-ON (MS-NON) vs HC eyes; and 3) MS-ON vs MS-NON eyes., Results: The OCT meta-analysis included 170 studies and 8542 HC, 5529 MS-ON, and 14,822 MS-NON eyes. MS-ON and MS-NON eyes had lower pRNFL and GCIPL thickness compared to HC. There was no difference in inner nuclear layer (INL) thickness between HC and MS; INL was thicker in MS-ON compared to MS-NON eyes. The OCTA meta-analysis included 24 studies and 1344 HC, 505 MS-ON, and 1168 MS-NON eyes. MS-ON and MS-NON eyes had lower peripapillary vessel density and macular superficial vessel density compared to HC. We also summarized 12 studies evaluating the diagnostic yield of inter-eye differences in OCT measurements for detecting unilateral optic nerve involvement., Conclusions: OCT allows for reliable quantification of retinal neuro-axonal damage in MS. In our review, we highlight studies demonstrating that OCT can establish robust thresholds for detecting unilateral optic nerve involvement., Competing Interests: Declaration of competing interest The authors declare that there is no conflict of interest., (Copyright © 2025 Elsevier B.V. All rights reserved.)

Water is a greatly convenient solvent in Raman spectroscopy. However, non-additive effects sometimes make its signal difficult to subtract. To understand these effects, spectra for clusters of model ions, including transition metal complexes and water molecules, were simulated and analyzed. A combined molecular mechanics/quantum mechanics approach was taken to reveal how relative Raman scattering intensities depend on the distance from the solute and the excitation wavelength. The computations indicate a big effect of solute charge; for example, the sodium cation affects Raman scattering by water to a lesser extent than the chlorine anion. The modeling was able to qualitatively reproduce the experimental observation that a solution of a simple salt may work as a baseline better than pure water in many Raman experiments. For absorbing species, an additional scattering boost occurs due to the resonance effect. Simulations thus provide useful insight into solute-solvent interactions and their effects on measured spectra., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Soils provide a range of essential ecosystem services for sustaining life, including climate regulation. Advanced technologies support the protection and restoration of this natural resource. We developed the first fine-resolution spectral grid of bare soils by processing a spatiotemporal satellite data cube spanning the globe. Landsat imagery provided a 30 m composite soil image using the Geospatial Soil Sensing System (GEOS3), which calculates the median of pixels from the 40-year time series (1984-2022). The map of the Earth's bare soil covers nearly 90 % of the world's drylands. The modeling resulted in 10 spectral patterns of soils worldwide. Results indicate that plant residue and unknown soil patterns are the main factors that affect soil reflectance. Elevation and the shortwave infrared (SWIR2) band show the highest importance, with 78 and 80 %, respectively, suggesting that spectral and geospatial proxies provide inference on soils. We showcase that spectral groups are associated with environmental factors (climate, land use and land cover, geology, landforms, and soil). These outcomes represent an unprecedented information source capable of unveiling nuances on global soil conditions. Information derived from reflectance data supports the modeling of several soil properties with applications in soil-geological surveying, smart agriculture, soil tillage optimization, erosion monitoring, soil health, and climate change studies. Our comprehensive spectrally-based soil grid can address global needs by informing stakeholders and supporting policy, mitigation planning, soil management strategy, and soil, food, and climate security interventions., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 Elsevier B.V. All rights reserved.)

Objective: This study aimed to assess the cost-effectiveness of lung cancer screening (LCS) employing volume-based low-dose computed tomography (LDCT) in contrast to the absence of screening, targeting an asymptomatic high-risk population in Greece, leveraging the outcomes derived from the NELSON study, the largest European randomized control trial dedicated to LCS., Methods: A validated model incorporating a decision tree and an integrated state-transition Markov model was used to simulate the identification, diagnosis, and treatments for a population at high risk of developing lung cancer, from a healthcare payer perspective. Screen-detected lung cancers, costs, life years (LYs), quality-adjusted life years (QALYs), and the incremental cost-effectiveness ratio (ICER) were predicted. Sensitivity and scenario analyses were conducted to assess the robustness and reliability of the model's outcomes under varying parameters and hypothetical situations., Results: Annual LCS with volume-based LDCT detected 17,104 more lung cancer patients at early-stage among 207,885 screening population, leading to 8,761 premature lung cancer deaths averted. In addition, in contrast to no screening, LCS yielded 86,207 LYs gained and 50,207 incremental QALYs at an additional cost of €278,971,940, resulting in an ICER of €3,236 per LY and €5,505 per QALY, over a lifetime horizon. These estimates were robust in sensitivity analyses., Conclusions: LCS with volume-based LDCT, targeting an asymptomatic high-risk population, is highly cost-effective in Greece. Implementing LCS ensures efficient allocation of public healthcare resources while delivering substantial clinical benefits to lung cancer patients., Competing Interests: X. Pan, K. Togka, and H. ten Berge are employees of the Institute for Diagnostic Accuracy, during the conducted of the study. A. Moraris is an employee of AstraZeneca. However, these organizations had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Additionally, this does not alter our adherence to PLOS ONE policies on sharing data and materials. The specific roles of these authors are articulated in the ‘author contributions’ section. M. Postma reports interests in Health-Ecore, and in PAG BV, both of which are unrelated to the submitted work. E. Zervas reports consultation and lecture fees from AstraZeneca, MSD, Novartis, and Bristol-Myers, and he serves as the Treasurer of Hellenic Thoracic Society, both of which are unrelated to the submitted work. G. Kourlaba, reports grants from Pfizer for other studies, which is unrelated to the submitted work. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed., (Copyright: © 2025 Pan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The treatment strategy for children and adolescents with chronic myeloid leukemia in the chronic phase (CML-CP) has evolved from allogeneic hematopoietic stem cell transplantation (HSCT) to tyrosine kinase inhibitors (TKIs). With the advent of next-generation TKIs and new targeted therapies in the CML field, an international pediatric CML expert panel provides recommendations based on the medical literature (including previous pediatric guidelines), national standards, and treatment principles used in adults with CML-CP. Recommendations include diagnosis of the disease and details on managing the initial steps of care of children and adolescents with newly diagnosed CML-CP, including complications such as leukostasis. The treatment recommendations are based on the initiation of therapy with a first- or second-generation TKI according to the allocated European Treatment and Outcome Study (EUTOS) long-term survival score risk group of the patient. The subsequent steps are based on the results of recommended monitoring which can justify a switch to another TKI or a drug in development if there is resistance or toxicity. The panel also provides recommendations regarding the discontinuation criteria for TKIs in children and adolescents in sustained deep molecular response. Allogeneic HSCT is not recommended as the first-line of treatment for children with CML-CP but is to be considered in case of progression to the advanced phase or failure of several lines of treatment. The present treatment and management recommendations are intended to provide advice to clinicians in view of optimizing the care and the outcome of children and adolescents with CML-CP., Competing Interests: Competing interests: The authors declare no competing interests., (© 2025. The Author(s), under exclusive licence to Springer Nature Limited.)

A quinazoline derivative containing a properly situated o -phenol ring, namely ( E )-2-((2-(quinazolin-4-yl)hydrazono)methyl)phenol (H2L), was synthesized in order to investigate the ability of this novel ligand for metal complexation. The interaction of deprotonated HL - with Zn(II) resulted in the mononuclear complex [Zn(HL) 2 ]·1.5CH 3 OH·H 2 O (complex 1). When doubly deprotonated ligand L -2 reacted with Cu(II), the tetranuclear complex [Cu 4 (L) 4 (DMF) 4 ]·8H 2 O (complex 2) was isolated, which can be described as an azametallacoronate compound. All three compounds (H2L and complexes 1 and 2) were characterized by spectroscopic techniques and single-crystal X-ray crystallography. The biological profile of the compounds was evaluated in regard to their affinity for calf-thymus DNA, the ability to cleave supercoiled circular pBR322 plasmid DNA in the absence or presence of irradiation of various wavelengths (UVA, UVB and visible light), their binding with bovine serum albumin and their capacity to scavenge 1,1-diphenyl-picrylhydrazyl and 2,2'-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) radicals and to reduce H 2 O 2 . The compounds can bind tightly to calf-thymus DNA via intercalation, and do not induce notable cleavage of plasmid DNA. They can bind tightly and reversibly to the albumin and have shown moderate antioxidant activity.

Dissolving microneedles (MNs) are promising transdermal drug delivery systems that can effectively increase the absorption of the drugs. They bypass the first layer of the skin, the stratum corneum (SC) and deliver the drugs directly into the dermis, by dissolving inside the interstitial fluid and releasing the active. The traditional ways of MN fabrication involve primarily micromolding, which basically uses silicone molds. Drugs and polymer mixture solutions are poured into these molds and after drying the MN arrays are carefully removed. In the present study, a novel molding process was employed to fabricate dissolving MNs containing rivastigmine (RIV). RIV is available as an oral tablet and a transdermal patch. The patch (Exelon®), used for managing Alzheimer's symptoms in mild to moderate dementia, releases only about 50 % of its drug content, raising concerns about dose wastage, environmental impact, and patient costs. Thus, RIV was selected as the model drug to fabricate MNs by combining to novel processes, Digital Light Processing and Free-D Molding, a Vacuum Compression Molding (VCM) Technique provided by MeltPrep®. The developed arrays were evaluated regarding their physiochemical characteristics and their ability to penetrate the skin without breaking or creating fragments, as they can withstand forces up to 600 N. The MNs were visualized using optical microscopy, SEM, and CLSM to examine their geometry, surface and length (0.708 mm). Permeability studies verified that the MNs can increase significantly RIV transportation across the skin, up to 9-fold. Histological analysis was conducted to ensure that the produced MNs are safe for transdermal applications. Overall, the present study suggests that Free-D molding, a combination of 3D printing and VCM can produce dissolving MN arrays that are effective and safe for transdermal applications., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025. Published by Elsevier B.V.)

Background: We investigated how cerebrospinal fluid levels of synaptic proteins associate with memory function in normal cognition (CN) and mild cognitive impairment (MCI), and investigated the effect of amyloid positivity on these associations., Methods: We included 242 CN (105(43%) abnormal amyloid), and 278 MCI individuals (183(66%) abnormal amyloid) from the European Medical Information Framework for Alzheimer's Disease Multimodal Biomarker Discovery (EMIF-AD MBD) and the Alzheimer's Disease Neuroimaging Initiative (ADNI). For 181 (EMIF-AD MBD) and 36 (ADNI) proteins with a synaptic annotation in SynGO, associations with word learning recall were analysed with linear models., Results: Subsets of synaptic proteins showed lower levels with worse recall in preclinical AD (EMIF-AD MBD: 7, ADNI: 5 proteins, none overlapping), prodromal AD (EMIF-AD MBD only, 27 proteins) and non-AD MCI (EMIF-AD MBD: 1, ADNI: 7 proteins). The majority of these associations were specific to these clinical groups., Conclusions: Synaptic disturbance-related memory impairment occurred very early in AD, indicating it may be relevant to develop therapies targeting the synapse early in the disease., Competing Interests: Declarations. Ethics approval and consent to participate: For both ADNI and EMIF-AD MBD, Local institutional review boards approved the procedures for this study and written informed consent was obtained in accordance with the Declaration of Helsinki. Supplementary Table 4 contains a full overview of Ethical Committee/IRB names of each center. Consent for publication: Not applicable. Competing interests: KB has served as a consultant, at advisory boards, or at data monitoring committees for Abcam, Axon, BioArctic, Biogen, JOMDD/Shimadzu. Julius Clinical, Lilly, MagQu, Novartis, Pharmatrophix, Prothena, Roche Diagnostics, and Siemens Healthineers, and is a co-founder of Brain Biomarker Solutions in Gothenburg AB (BBS), which is a part of the GU Ventures Incubator Program, outside the work presented in this paper. HZ has served at scientific advisory boards and/or as a consultant for Abbvie, Alector, Annexon, Artery Therapeutics, AZTherapies, CogRx, Denali, Eisai, Nervgen, Pinteon Therapeutics, Red Abbey Labs, Passage Bio, Roche, Samumed, Siemens Healthineers, Triplet Therapeutics, and Wave, has given lectures in symposia sponsored by Cellectricon, Fujirebio, Alzecure, Biogen, and Roche, and is a co-founder of Brain Biomarker Solutions in Gothenburg AB (BBS), which is a part of the GU Ventures Incubator Program. PS has acquired grants for the institution from GE Healthcare and Piramal and received consultancy/speaker fees paid to the institution from Novartis, Probiodrug, Biogen, Roche, and EIP Pharma, LLC in the past 2 years. CT received grants from the European Commission, the Dutch Research Council (ZonMW), Association of Frontotemporal Dementia/Alzheimer’s Drug Discovery Foundation, The Weston Brain Institute, Alzheimer Netherlands. Prof. dr. Teunissen has functioned in advisory boards of Roche, received non-financial support in the form of research consumables from ADxNeurosciences and Euroimmun, performed contract research or received grants from Probiodrug, Biogen, Esai, Toyama, Janssen Prevention Center, Boehringer, AxonNeurosciences, EIP farma, PeopleBio, Roche. The other authors report no conflict of interest., (© 2025. The Author(s).)

Pre-eclampsia, placental abruption, and fetal growth restriction (FGR) are collectively referred to as placental ischemic disease (PID). Heat shock proteins (HSPs), originally considered as a response to the heat shock, have a central role in regulating the cellular functions by quality controlling the newly synthesized proteins. The aim of the present review is to investigate the expression of the HSPs in PID and their potential role as biomarkers, based on the available data in the literature. A considerable amount of research has been conducted in order to determine the significance of HSPs in placental pathology and insufficiency, using both immunochemistry and circulating mRNA approaches. HSPs seem to be promising biomarkers that could be used for screening and monitoring the cellular stress of the placenta and its dysfunction. Yet, in order to be able to reach more solid evidence and draw a safer conclusion regarding their utility in clinical practice there is still a long way to go and further well-designed greater scale studies are required., (© 2025 The Author(s). International Journal of Gynecology & Obstetrics published by John Wiley & Sons Ltd on behalf of International Federation of Gynecology and Obstetrics.)

Background: Soccer is a contact sport during which participants risk injury, including due to concussion. Interestingly, the task most frequently associated with concussions is the act of heading the ball. This study seeks to answer the following research question: Does an acute playing of purposeful soccer heading in female football players lead to changes in BESS normative outcomes and balance? Additionally, we aim to explore the relationship between a gold-standard BESS Test and a Balance Test performed on a force plate., Methods: This project involved twenty-eight female soccer players (age = 19.6 + 2.96 years, mass = 60.4+ 5.3 kg, and height = 163.6 + 6.4 cm). pre and post the heading condition and the results of the Wilcoxon Signed Ranks Test. The participants were healthy and underwent BESS monitoring on a force plate before and after heading and footing training. Standard 450 g soccer balls were utilized. Participants performed ten headers for the header condition and ten footers for the footer condition. Resultant sway velocity and BESS error outcomes were calculated before and after heading and footing training. I need a brief description of the statistical approach here., Results: Statistically significant increases after the heading condition were found for Single Leg Stance (COP PATH) score (Z = -3.986, p = 0.000), BESS score on foam surface (Z = -2.511, p = 0.012), BESS score on firm surface (Z = -2.353, p = 0.019). A statistically significant increase after the footer condition was found for the Tandem Stance (mm2) score (Z = -2.900, p = 0.004). A statistically significant difference between the group conditions was found in the post-BESS score foam difference (U = 268.500, p = 0.042). BESS score foam mean increase was 1.93 after the heading condition and 0.21 after the footer condition., Conclusion: This pilot study not only tests the feasibility of using force plates to measure BESS outcomes after heading in female soccer but also underscores the effectiveness of using BESS parameters to evaluate changes in balance function following heading compared to a control footer condition. The findings of this study provide valuable insights into the potential effects of soccer on balance in female players, contributing to the body of knowledge in sports medicine and physical education., Level of Evidence: 3., Competing Interests: The authors have no conflicts of interest., (© The Author(s).)

Managing dual antiplatelet therapy (DAPT) perioperatively is challenging, especially in patients who have recently undergone percutaneous coronary intervention (PCI). Intravenous antiplatelet agents are recommended in these cases. This case series describes the perioperative management of two high bleeding risk patients with recent PCI undergoing cardiac and non-cardiac surgeries using cangrelor monotherapy.

Background: Disease-free survival is the main outcome of interest considered when assessing the effectiveness of surgical management of papillary thyroid carcinoma (PTC). Specific characteristics of nodal metastases have been demonstrated to impact the risk of recurrence., Objective: Verify the oncologic rationale of prophylactic central compartment neck dissection (pCCND) in the management of PTC by comparing the pathologic spectrum of lymph nodes in patient's undergoing pCCND vs. therapeutic CCND (tCCND)., Methods: Between May 2017 and October 2018, 257 patients underwent total thyroidectomy for PTC. pCCND was performed for clinically uninvolved nodes, and tCCND for clinically apparent nodal disease. Harvested metastatic nodes from each group were compared in terms of number, size, and the presence of extranodal extension. Cut-off values for the size and number were 2 mm and 5, respectively. Patients were followed until October 2023., Results: 78 patients underwent tCCND. Whereas pCCND was performed in 179 patients. The mean number of nodes harvested in tCCND was 14 (9-31), and 9 (5-24) in pCCND (p < 0.0001). Node positivity was 84.6, and 37.4%, respectively (p < 0.0001). ≥5 metastatic nodes were harvested in 66.6% of tCCND vs. 7.5% of pCCND (p < 0.0001). 73% of tCCND had a metastatic node ≥2 mm in size vs. 2.5% of pCCND (p < 0.0001). Extranodal extension occurred in 25% of tCCND vs. 2.5% of pCCND (p = 0.01). Recurrence rate was 3.8% in tCCND vs. none in pCCND (p = 0.008)., Conclusion: Clinically inapparent nodal disease has a pathological spectrum with insignificant impact on disease recurrence. Therefore, pCCND does not seem to be oncologically meaningful., Competing Interests: Compliance with ethical standards. Conflict of interest: The authors declare no competing interests. Ethical approval: All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. This research obtained the Institutional Review Board (IRB) approval (No. 6/5/2023/2024). Informed consent: Patients’ informed consents were obtained. The research was conducted committing to the institute’s scientific research policy that ensures maintaining data confidentiality and using it for scientific purposes only., (© 2025. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Early identification of kidney disease can protect kidney health, prevent kidney disease progression and related complications, reduce cardiovascular disease risk, and decrease mortality. We must ask "Are your kidneys ok?" using serum creatinine to estimate kidney function and urine albumin to assess for kidney and endothelial damage. Evaluation for causes and risk factors for chronic kidney disease (CKD) includes testing for diabetes and measurement of blood pressure and body mass index. This World Kidney Day we assert that case-finding in high-risk populations, or even population level screening, can decrease the burden of kidney disease globally. Early-stage CKD is asymptomatic and simple to test for, and recent paradigm shifting CKD treatments such as sodium glucose co-transporter-2 inhibitors dramatically improve outcomes and favor the cost-benefit analysis for screening or case-finding programs. Despite this, numerous barriers exist, including resource allocation, health care funding, health care infrastructure, and health care professional and population awareness of kidney disease. Coordinated efforts by major kidney nongovernmental organizations to prioritize the kidney health agenda for governments and aligning early detection efforts with other current programs will maximize efficiencies., (Copyright © 2025 World Kidney Day Steering Committee. Published by Elsevier Inc. All rights reserved.)

Water resources face significant threats from pollutants identified as Persistent Mobile Organic Compounds (PMOCs). These substances are known for their affinity for water, resistance to environmental degradation, and potential adverse effects on human health and the environment, particularly when classified as toxic. Accordingly, a three-year monitoring study (2021-2023) was carried out at a WWTP in Northern Greece (Thessaloniki), utilizing High-Resolution Mass Spectrometry (HRMS) technology to detect (potentially) PMOCs. The monitoring process was based on two basic approaches of HRMS analysis: target and suspect screening. A total number of 2500 different potential PMOCs list was created based on the available literature. Fifty-five of them were identified with the target analysis approach in at least one sample. The results indicated that antihypertensives and beta-blockers were among the most frequently detected PMOCs categories during the sampling period. Specifically, valsartan and irbesartan exhibited substantial increases in concentration, surpassing 5000 ng/L in influent samples and 1000 ng/L in effluent samples. Additionally, the study employed suspect analysis, incorporating potential substances from the literature to enhance the monitoring program. As a result, the list of identified compounds was expanded by 16 additional compounds with a confidence level of 2b identification. This was complemented by retrospective analysis techniques to identify compounds that are challenging to obtain as standard compounds. The study culminated in an estimation of the environmental risks. The findings highlight the ecological risks associated with elevated PMOCs levels and emphasize the need for continuous monitoring and regulatory measures to mitigate potential environmental impacts. Finally, the study contributes to understanding the complex interactions between environmental factors, PMOCs consumption, and pollution in wastewater treatment plants., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 Elsevier B.V. All rights reserved.)

Heart failure (HF) remains a significant public health challenge with high mortality rates. Machine learning (ML) techniques offer a promising approach to predict HF mortality, potentially improving clinical outcomes. However, the effectiveness of these techniques heavily depends on the quality and relevance of the features used. This study introduces a novel hybrid feature selection methodology that combines Extremely Randomized Trees (Extra-Trees) and non-linear correlation measures to enhance 1-year all-cause mortality prediction in HF patients using echocardiographic and key demographic data. Unlike existing feature selection methods that are often tied to specific ML models and produce inconsistent feature sets across different algorithms, our proposed approach is model-independent, ensuring robustness and generalizability. Moreover, the optimal number of predictive features is identified through loss graph inspection, leading to a compact and highly informative subset of seven features. We trained and evaluated seven widely-used ML models on both the full feature set and the selected subset, finding that most models maintained or improved their predictive performance despite an 80% reduction in features. Model interpretability was enhanced using SHapley Additive exPlanations (SHAP), allowing for a detailed examination of how individual features influence predictions. To further assess its effectiveness, we compared our methodology against widely known feature selection techniques across all seven ML models. The results underscore the superiority of our proposed feature set in accurately predicting HF mortality over conventional methods, offering new opportunities for personalized management strategies based on a streamlined and explainable feature subset., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 Elsevier Inc. All rights reserved.)

In the context of the URBANOME project, aiming to assess European citizens' exposure to air pollutants (PM10, PM2.5, NO2) and noise, an extensive data collection process was undertaken. This involved the distribution of stationary home sensors, portable sensors, and smartphone applications, alongside participants logging their activities while using these devices. By leveraging socioeconomic and socio-demographic statistical data for the residents of Thessaloniki, we developed an agent-based model to estimate exposure levels based on the movement patterns, locations, and data collected from the URBANOME campaign. The model highlights that an individual's exposure is closely linked to the type of activities they perform, their location, age, and gender. Whether exposure occurs indoors, or outdoors is important for determining intake levels. Activity selections were found to be strongly influenced by income, age, and social connections, indicating that socio-economic factors significantly shape exposure patterns. The analysis also revealed considerable differences between PM measurements taken from fixed monitoring stations and the sensors used in the campaign. Notably, even agents residing in the same household displayed distinct exposure levels, underscoring the variability within localized environments. Preliminary results from the URBANOME campaign were compared with the ABM outputs, showing differences in median values of up to 20 % of both noise and inhalation intakes. This research emphasizes the importance of using such models for developing future scenarios in large cities aimed at fostering green transitions and enhancing citizens' quality of life. These models provide valuable insights for designing strategies to reduce exposure and improve urban living conditions., Competing Interests: Declaration of competing interest The author(s) declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 The Authors. Published by Elsevier B.V. All rights reserved.)

The atmospheric occurrence and partition between the gas and particulate phase of short- (PCAs-C 10-13 ) and medium-chain (PCAs-C 14-17 ) polychlorinated alkanes (PCAs) were investigated during two sampling campaigns in Athens city, Greece. The concentrations of PCAs ranged between 1.46 and 43.6 ng m -3 in the gas phase, and between 5.8 and 40.3 ng m -3 in the particulate phase, which were within the reported levels in Europe. Significant seasonal variation was observed for PCAs-C 10-13 and PCAs-C 14-17 in the gas phase. C 10 Cl 6-7 and C 14 Cl 6-8 were the predominant short- and medium-chain congeners, respectively. Gas-phase PCAs exhibited significant positive correlation with temperature, and negative correlation with relative humidity. Diagnostic ratios of medium to short-chain PCAs suggested that ΣPCAs in total suspended particle (TSP) mainly originated from local sources. Furthermore, the relationship between partitioning coefficient Kp and the subcooled liquid pressure (P L °) was investigated. Moreover, Positive Matrix Factorization (PMF) analysis was employed to identify the potential ΣPCAs groups of sources. Finally, the estimated risk of inhalation exposure to ΣPCAs for adults and children was found to be low., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 Elsevier Ltd. All rights reserved.)

Surrogacy is the assisted reproductive technology (ART) practice in which a person becomes pregnant, carries, and delivers a child on behalf of another couple/person, who are the intended parent(s). Surrogacy is an especially complex practice as the interests of the intended parents, the gestational carrier, and the future child may differ. This paper considers ethical questions related to different forms of surrogacy. It concludes that non-commercial surrogacy is an acceptable method of assisted reproduction for specific indications. When using surrogacy to form a family, it is essential that there are measures to protect all parties, to guarantee well-considered decision-making, and to minimize risks. The current paper formulates recommendations to promote these measures. This paper is an update to the ESHRE Task Force Ethics and Law Paper 10: Surrogacy and replaces this paper., (© The Author(s) 2025. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology.)

Introduction: Α customized organ-on-a-chip microfluidic device was developed for dynamic culture of oral mucosa equivalents (Oral&#95;mucosa&#95;chip-OMC)., Materials and Methods: Additive Manufacturing (AM) was performed via stereolithography (SLA) printing. The dimensional accuracy was evaluated via microfocus computed tomography (mCT), the surface characteristics via scanning electron microscopy (SEM), while the mechanical properties via nanoindentation and compression tests. Computational fluid dynamics (CFD) optimized net forces towards the culture area. An oral mucosa equivalent comprising a multilayered epithelium derived by culture of TR146 cells at the air-liquid interface (ALI) and a lamina propria-analogue based on a collagen-I/fibrin hydrogel was maintained under ultra-precise flow conditions., Results: An open-type device concept encompassing two interconnected chambers for long-term dynamic culture was developed and characterized for AM parameters, mechanical and biological properties. The split-inlet flow channel architecture allowed even distribution and symmetric flow velocity to the culture area. Cell viability exceeded 90%, while mCT and SEM indicated the 0° building angle as the most accurate SLA condition. CFD further showed that the 0° and 30° building angles most accurately reproduced the channel flow velocity predicted by the initial CAD model., Conclusion: This study developed a customized, easy-to-produce, and cell-friendly OMC device, providing a 3D tool for biocompatibility assessment of biomaterials., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Objective: Intranasal esketamine has been approved as an adjunctive therapy for treatment-resistant major depressive disorder with acute suicidal ideation and behavior. The authors conducted a systematic review and meta-analysis of the available data on its efficacy against depression and suicidality as well as its side effects., Methods: MEDLINE was searched with the keyword "esketamine" on March 24, 2024, using the PRISMA method. Data processing and statistical analysis were performed with R, version 4.3.3, and the meta-analysis was performed with the METAFOR package., Results: Of 1,115 articles initially identified, 87 were included for analysis and discussion. At weeks 2-4, randomized controlled trials were mostly negative or failed; however, the meta-analysis returned a weak but significant positive effect for depression (effect size range, 0.15-0.23 at weeks 2-4), similar to augmentation strategies with atypical antipsychotics for treatment-resistant depression. The effect size concerning suicidality was not significant at any time point. The sensitivity analysis produced the same results., Conclusions: The study findings suggest that esketamine's efficacy as an add-on to antidepressants is modest in treatment-resistant depression (similar to augmentation strategies with atypical antipsychotics) and is absent against suicidality itself. These findings need to be considered in light of esketamine's abuse potential and the fact that long-term effects are still not fully known. Some alarming signs concerning deaths and emerging suicidality during the testing phase are discussed, along with other regulatory issues., Competing Interests: Dr. Saitis has received support to participate in congresses from Innovis Pharma and Ricordatti. Dr. Schatzberg has served as a consultant for Alto Neurosciences, ANeurotech, Delpor, Douglas Pharmaceuticals, Galen, HMNC, Johnson & Johnson, Magnus, Mindful Health Solutions, NeuraWell, Owl Insights, Sage, Skyland Trail, Soneira, and Tris; and he has equity in Alto Neurosciences, ANeurotech, Corcept, Madrigal, Magnus, Mindful Health Solutions, NeuraWell, Seattle Genetics, Soneira, and Titan. Dr. Fountoulakis reports no financial relationships with commercial interests.

A peritoneal mesothelial cyst is a rare entity, commonly asymptomatic, which is usually detected as an incidental radiological finding and needs surgical intervention for complete removal. We present a unique case of a peritoneal simple mesothelial cyst that was removed accidentally during peritoneal dialysis in a pediatric patient., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Chronic rhinosinusitis (CRS) poses significant challenges in surgical management due to the lack of clear guidelines, particularly in type 2 CRS. This review focuses on surgical approaches for primary diffuse type 2-dominant CRS, emphasizing preoperative and intraoperative strategies., Methods: A consensus group, comprising experts from Europe, United Kingdom, Australia, South Africa, North and South America, was assembled. Using a modified Delphi method, 67 statements were formulated following a literature review, with an additional statement added in the second iteration. Final recommendations were discussed during a consensus meeting in Santorini, Greece, in October 2023., Results: Out of the 68 proposed statements, consensus was achieved on 45. Most (34) statements received a median score of 7 (strongly agree), and 11 had a median score of 6 (agree). The finalized recommendations cover the indications, timing, extent of surgery, and intraoperative management for both primary and revision surgery in primary diffuse type 2-dominant CRS. A key focus is on complete sinus surgery, which involves creating a neo-sinus cavity by removing bone partitions in the ethmoid and opening the frontal and sphenoidal sinuses as needed. Adequate primary and revision surgery includes clearing all nasal polyps and diseased mucosa while ensuring ideal conditions for topical therapy. Additionally, there was consensus on performing complete sinus surgery before considering monoclonal antibody therapies, unless contraindicated., Conclusion: These 45 consensus statements, derived from both current evidence and expert opinion, provide valuable guidance for clinicians in the surgical management of primary diffuse type 2-dominant CRS., (© 2025 The Author(s). International Forum of Allergy & Rhinology published by Wiley Periodicals LLC on behalf of American Academy of Otolaryngic Allergy and American Rhinologic Society.)

Background: To assess the safety and efficacy of flush endovenous laser ablation (fEVLA) in the treatment of chronic venous insufficiency (CVI)., Methods: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines, a systematic review aiming to identify studies published from inception to March 2024 was conducted. The investigation covered single-arm studies and studies comparing fEVLA to standard EVLA (sEVLA). The primary endpoint was endovenous heat-induced thrombosis (EHIT) class ≥ II., Results: Eleven studies encompassing 2738 patients and 3147 truncal veins were included. The pooled EHIT ≥ II was 1.37% (95% CI: 0.57-3.28). Meta-regression identified an association between linear endovenous energy density (LEED) applied at the saphenofemoral junction (SFJ) and EHIT ≥ II outcomes (β = 0.011, P < 0.01). The pooled medium-term great saphenous vein (GSV) occlusion was 97.59% (95% CI: 94.89-98.88). The pooled and crude deep vein thrombosis (DVT) and pulmonary embolism (PE) estimates were 0.97% (95% CI: 0.64-1.47) and 0.04%. The comparative analysis regarding GSV occlusion, odds ratio (OR) 3.26 (95% CI: 0.76-13.97) and refluxing anterior accessory saphenous vein (AASV), risk ratio (RR) 0.45 (95% CI: 0.11-1.77) suggested a nonstatistically significant trend favoring fEVLA. Nonstatistically significant differences were identified in terms of EHIT ≥ II between the techniques, RR 1.00(95% CI: 0.18-5.53). Statistically significant differences favoring fEVLA were identified in terms of proximal groin recurrence RR 0.35 (95% CI: 0.16-0.80) and stump length (mean difference) MD -7.23 (95% CI: -11.59to-2.88)., Conclusion: This review has demonstrated the safety of fEVLA while also suggesting a potentially improved efficacy of fEVLA over sEVLA in terms of proximal groin recurrence. Moreover, the trend indicating fEVLA's superiority in terms of GSV occlusion and the occurrence of new-onset AASV reflux merits further research., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background and Aims: Portal hypertension is a serious complication of cirrhosis, which leads to life-threatening complications. HVPG, a surrogate of portal pressure, is the reference standard test to assess the severity of portal hypertension. However, since HVPG is limited by its invasiveness and availability, noninvasive liver disease assessments to assess portal pressure, especially clinically significant portal hypertension (CSPH), are needed., Approach and Results: We conducted a systematic review of Ovid MEDLINE(R) Ovid EMBASE, Ovid Cochrane Central Register of Controlled Trials, Ovid Cochrane Database of Systematic Reviews, and Scopus from each database's inception to April 22, 2022. We included only studies in English that examined ≥50 patients in single liver disease etiologies, which compared noninvasive tests (blood and/or imaging) to HVPG for predicting clinically significant portal hypertension (CSPH; defined as HVPG ≥ 10 mm Hg) in patients with chronic liver disease. Outcomes included measures of diagnostic test accuracy. Additionally, a narrative review of studies not eligible for the systematic review is also provided. Nine studies with 2492 patients met the inclusion criteria. There was substantial heterogeneity with regard to liver disease studied and cutoff values used to detect CSPH. Blood-based tests, including aspartate-to-platelet ratio index (APRI) (56% sensitivity and 68% specificity) and FIB-4 (54% sensitivity and 73% specificity) had low accuracy measures. Imaging-based tests (transient elastography and shear wave elastography detection of liver stiffness measurement [LSM]) had better accuracy but also had substantial variation; at 15 kPa, TE sensitivity was 90%-96% and specificity was 48%-50%, while at 25 kPa, its sensitivity and specificity were 57%-85% and 82%-93%, respectively. The narrative review suggested that imaging-based tests are the best available noninvasive liver disease assessment to detect CSPH; CSPH is highly unlikely to be present at an LSM ≤15 kPa and likely to be present at an LSM ≥25 kPa., Conclusions: While imaging-based noninvasive liver disease assessment appeared to have higher accuracy than blood-based tests to detect CSPH, only 9 studies fit the a priori established inclusion criteria for the systematic review. In addition, there was substantial study heterogeneity and variation in cutoffs for LSM to detect CSPH, limiting the ability to establish definitive cutoffs to detect CSPH., (Copyright © 2024 American Association for the Study of Liver Diseases.)

Background:  Symptomatic cerebral vasospasms are deleterious complication of the rupture of a cerebral aneurysm and potentially lethal. The existing scales used to classify the initial presentation of a subarachnoid hemorrhage (SAH) offer a blink of the outcome and the possibility of occurrence of symptomatic cerebral vasospasms. Altogether, neither are they sufficient to predict outcome or occurrence of events reliably nor do they offer a united front. This study tests the common grading scales and factors that otherwise affect the outcome, in an artificial intelligence (AI) based algorithm to create a reliable prediction model for the occurrence of cerebral vasospasms., Methods:  Applying the R environment, an easy-to-operate command line was programmed to prognosticate the occurrence of vasospasms. Eighty-seven patients with aneurysmal SAH during a 24-month period of time were included for study purposes. The holdout and cross-validation methods were used to evaluate the algorithm (65 patients constituted the validation set and 22 patients constituted the test set). The Support Vector Machines (ksvm) classification method provided a high accuracy. The medical dataset included demographic data, the Hunt and Hess scale (H&H), Fisher grade, Barrow Neurological Institute (BNI) scale, length of intervention for aneurysmal repair, etc. RESULTS:  Our prediction model based on the AI algorithm demonstrated an accuracy of 61 to 86% for the event of symptomatic vasospasms. For subgroup analysis, 28.8% ( n  = 13) patients in the surgical cohort developed symptomatic vasospasm. Of these, 50% ( n  = 7) were admitted with Fisher scale grade 4, 37.5% ( n  = 5) with H&H 5, and 28.5% ( n  = 4) with BNI 5. In the endovascular cohort, vasospasms occurred in 31.8% ( n  = 14) patients. Of these, 69% ( n  = 9) patients were admitted with Fisher grade 4, 23% ( n  = 3) patients with H&H 5, and 7% ( n  = 1) patients with BNI 5., Conclusion:  From our data, we may believe that the algorithm presented can help in identifying patients with SAH who are at "high" or "low" risk of developing symptomatic vasospasms. This risk balancing might further allow the treating physician to go for an earlier intervention trying to prevent permanent sequelae. Certainly, accuracy will improve with a higher caseload and more statistical coefficients., Competing Interests: None declared., (Thieme. All rights reserved.)

Introduction: The COVID-19 pandemic has had impact on global healthcare and respiratory disease patterns. The aim was to evaluate the changes in positive respiratory cultures during the pandemic., Methods: A retrospective analysis of respiratory specimens in Papanikolaou Hospital during 2018-2023 was performed. In total, 18,852 samples (12,277 males, 6575 females) of respiratory samples were recorded., Results: During 2018-2019, 684 BAL samples were received, of which 12.3 % were positive. Positive pharyngeal smears constituted 24.8 %, compared to 18.5 % in pandemic years, and 29.6 % in 2023. In PTC, pre-pandemic, positives were 12.3 %, while in 2021 the maximum percentage of positives (21.9 %) was observed. Positive levels remained high in 2023 (18.3 %). Concerning bronchial secretions, there was an increase (55.3 % in 2022 vs 47.0 % in 2019). The predominant bacteria were Acinetobacter spp, Klebsiella spp and Pseudomonas spp., Conclusion: Except for the bronchial secretions, the rest of the respiratory specimens do not exhibit any definite trends., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 Elsevier Inc. All rights reserved.)

Aims: A novel noninvasive score, Agile-4 score, combining liver stiffness measurements, aspartate aminotransferase/alanine aminotransferase, platelet count, diabetes status and sex has been developed for the identification of cirrhosis in patients with metabolic dysfunction-associated steatotic liver disease (MASLD). We assessed the performance of Agile-4 for ruling-in/out liver cirrhosis in MASLD patients., Materials and Methods: We searched Medline, Cochrane library, Web of science, Scopus and Echosens website up to May 2024. Eligible studies assessed the accuracy of Agile-4 for ruling-in (≥0.565) and ruling-out (<0.251) liver cirrhosis, using biopsy as the reference standard, at predefined thresholds. We calculated pooled sensitivity and specificity estimates for both Agile-4 thresholds alongside 95% confidence intervals following bivariate random-effect models. We assessed the risk of bias using Quality Assessment of Diagnostic Accuracy Studies-2 tool., Results: We included seven studies with 6037 participants. An Agile-4 score ≥0.565 yielded a pooled specificity of 0.93 (95% CI, 0.86-0.97). Similarly, an Agile-4 score <0.251 excluded cirrhosis with a summary sensitivity of 0.90 (0.80-0.95). Assuming a cirrhosis prevalence of 30%, the positive predictive value (PPV) for ruling-in cirrhosis was 80%, while the negative predictive value for ruling-out cirrhosis was 95%. Most studies were at high or unclear risk for bias due to concerns regarding patient selection and the blinding status of Agile-4 score interpretation in relation to biopsy results., Conclusions: Agile-4 score performs well for ruling-in/out liver cirrhosis in MASLD patients. Owing to the relatively low PPV, sequential application of the Agile-4 after fibrosis-4 index (FIB-4) testing might further enhance its performance., (© 2024 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Background: Electromyographic (EMG) recordings indicate that both the flexor digitorum brevis and soleus muscles contribute significantly to the control of standing balance, However, less is known about the adjustments in EMG activity of these two muscles across different postures., Research Question: The purpose of our study was to use deep-learning models to distinguish between the EMG activity of the flexor digitorum brevis and soleus muscles across four standing postures., Methods: Deep convolutional neural networks were employed to classify standing postures based on the temporal and spatial features embedded in high-density surface EMG signals. The EMG recordings were obtained with grid electrodes placed over the flexor digitorum brevis and soleus muscles of healthy young men during four standing tasks: bipedal, tandem, one-leg, and tip-toe., Results and Significance: Two-way repeated-measures analysis of variance demonstrated that the model achieved significantly greater classification accuracy, particularly during tandem stance, using EMG data from flexor digitorum brevis compared with soleus muscle. Average classification accuracy was 84.6 % for flexor digitorum brevis and 79.1 % for soleus. The classification accuracy of both muscles varied across the four postures. There were significant differences in classification accuracy for flexor digitorum brevis between bipedal and tandem stances compared with one-leg and tip-toe stances. In contrast, the EMG data for soleus were only significantly different between bipedal stance and one-leg stance. These findings indicate that flexor digitorum brevis exhibited more distinct adjustments than soleus in the temporo-spatial features of EMG activity across the four postures., Competing Interests: Declaration of Competing Interest The authors declare no known competing financial interests or personal relationships that could influence the work reported in this article., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Study Objectives: To assess the impact of the non-respiratory arousal burden at baseline polysomnography (PSG) on residual daytime sleepiness in positive airway pressure (PAP)-treated obstructive sleep apnea (OSA)., Methods: We included OSA patients from the European Sleep Apnea Database registry with available arousal data who had at least 2 treatment follow-up visits. The primary outcome was the Epworth Sleepiness Scale (ESS) score under PAP. The non-respiratory arousal ratio (NRAR) was defined as the ratio of non-respiratory to total arousals at baseline PSG. A linear mixed model tested the effect of NRAR tertiles on residual sleepiness. Baseline variables that differed significantly between groups were included as covariates., Results: 800 patients with OSA (69.6 % male, mean age 57.1 ± 12.0 years, mean NRAR 0.22 ± 0.20) were evaluated during three follow up visits at a mean of 197.4, 499.3, and 731.6 days after PAP initiation. The interaction between time and NRAR tertile was statistically significant (F = 4.55, p = 0.001). The lowest NRAR tertile was associated with lower residual sleepiness over time compared to the highest NRAR tertile. The associations were independent of sex, comorbidities, body mass index, blood pressure, baseline apnea-hypopnea index, and baseline ESS score., Conclusions: NRAR at baseline PSG predicts residual sleepiness in PAP-treated OSA patients. The findings offer new insights into OSA phenotyping and have important implications for patient care., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: The ESADA network reports financial support was provided by European Cooperation in Science and Technology. The ESADA network reports financial support was provided by European Respiratory Society. Ludger Grote and the ESADA network reports financial support was provided by Bayer AG. Jean-Louis Pepin reports a relationship with French National Research Agency that includes: funding grants. Jean-Louis Pepin reports a relationship with Grenoble Alpes University Foundation that includes: funding grants. Sophia Schiza and Winfried Randerath serve in the editorial board of the submitting journal. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 Elsevier B.V. All rights reserved.)

The aim of the present systematic review was to evaluate the existing data on the health impacts, of the consumption of organically grown foods versus conventionally farmed alternatives, with specific focus on the postulated health superiority of organic foods. A systematic literature research was performed in PubMed, Embase, Web of Science, and Google Scholar. Inclusion criteria were articles on adults (>18 years of age) consuming organic foods for ≥6 months, written in English language, and provision of comparative results between conventional and organic nutrition regarding health indices. From 1760 identified references, 21 primary research articles (2006-2022) met the inclusion criteria. Outcomes related to chronic disease prevalence, biomarker effects, and exposure to pesticides and other harmful substances were evaluated. A significant inverse relationship between organic food consumption and cardiometabolic risk factors, including obesity, diabetes mellitus, hypertension, and hyperlipidemia, was observed in the majority of prospective studies. The data on cancer risk and nutrient value comparison between organic and conventional foods were inconclusive. Clinical trials consistently indicated lower pesticide exposure in participants on organic diets, suggesting potential health benefits. The consumption of organic foods is associated with reduced cardiometabolic risks and pesticide exposure. However, the long-term impact on cancer risk remains undetermined. Future long-term studies are needed to establish whether an organic diet is superior to a conventional one in terms of overall health benefits., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Purpose: Heart failure (HF) and atrial fibrillation (AF) are highly prevalent in hemodialysis. They are well-known significant modifiers of the disease associations with cardiovascular outcomes, but there is a lack of evidence regarding the effects of HF and AF on cardiorespiratory fitness. This study is the first to examine the possible association of the presence of HF and AF with exercise intolerance in patients undergoing hemodialysis., Methods: This analysis included 40 sex- and age-matched participants [10 hemodialysis patients with HF or AF, 10 hemodialysis patients without HF or AF, 10 patients with HF or AF without chronic kidney disease (CKD) and 10 healthy controls] that underwent CPET and spirometry examinations. The total of patients with HF had preserved ejection fraction., Results: VO2peak(ml/kg/min) showed a graded increase between hemodialysis patients with HF or AF, hemodialysis patients without HF or AF, non-CKD patients with HF or AF and controls (13.17 ± 2.45 vs 15.26 ± 3.29 vs 19.64 ± 5.84 vs 25.11 ± 6.94 ml/kg/min, p < 0.001); VO2peak(ml/min) followed the same pattern (1172 ± 197 vs 1269 ± 314 vs 1817 ± 583 vs 1952 ± 592 ml/min respectively, p = 0.001). VO2peak(%predicted), VO2AT(ml/kg/min), VO2AT(ml/min) and maximal work load significantly differed between the study groups, with a tendency for higher values from hemodialysis patients to non-CKD patients with HF or AF and to healthy controls. FEV1 and FVC levels were similar between the study groups. In the whole population, VO2peak(ml/kg/min) showed a positive correlation with hemoglobin (r = 0.663, p < 0.001) and negative correlations with high-sensitivity cardiac troponin I (r = - 0.493, p = 0.001) and BNP (r = - 0.479, p = 0.002)., Conclusion: Hemodialysis patients have low exercise tolerance, and the presence of HF or AF is associated with further decreased values of VO2peak, the most important determinant of cardiorespiratory fitness., Competing Interests: Declarations. Conflict of interest: All authors disclose that they do not have any financial or other relationships, which might lead to a conflict of interest regarding this paper. Ethics approval: All procedures were performed in line with the principles of the Declaration of Helsinki (2013 Amendment). The study protocol was reviewed and approved by the Ethics Committee of the School of Medicine, Aristotle University of Thessaloniki, and by the Institutional Review Board of Hippokration Hospital. Informed written consent was obtained for all participants prior to study enrollment., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Delivering valvular intervention for all eligible patients with valvular heart disease (VHD) in a timely manner remains a challenge. Therefore, a high number of patients with heart failure (HF) and VHD receive pharmacotherapy while awaiting intervention or as destination therapy if they are deemed inoperable. The sodium-glucose co-transporter-2 inhibitors (SGLT2i) are recommended with a class I indication for patients with chronic HF throughout the spectrum of left ventricular ejection fraction. However, all randomized trials of SGLT2i in HF patients have consistently excluded patients with significant VHD. Considering the proven benefit of SGLT2i for stable outpatients and acutely hospitalized patients with HF, SGLT2i could potentially be used for patients with HF secondary to significant VHD. This article highlights the unmet need to produce robust clinical evidence for the pharmacological management of patients with HF and significant VHD while summarizing the potential benefit from SGLT2i in the management of these patients., Competing Interests: Declarations. Conflict of interest: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Epilepsy imposes substantial challenges on informal caregivers, who play a vital role in supporting individuals with this condition. This review aims to explore the burden experienced by informal caregivers of adults with epilepsy and identify critical factors that influence their overall experience. A literature review was conducted following PRISMA guidelines. PubMed and ScienceDirect were searched for identifying original research articles published in English from January 2005 till the end of February 2024. Studies were critically appraised using the AXIS Critical Appraisal Tool for Cross-Sectional Studies. Data were extracted and a narrative synthesis was performed. Twelve studies involving 1.265 participants were included. Eight studies were rated as high quality, while four were rated as fair quality. Six primary determinants of caregiver burden were identified: care-recipient characteristics, caregiver characteristics, psychological and physical factors, availability of support system, ethnicity and culture, and stigma. The majority of studies reported mild-to-moderate levels of caregiver burden, reflecting the diverse challenges faced by caregivers providing assistance to adults with epilepsy. While this review identifies several factors influencing caregiver burden, prospective longitudinal and qualitative studies are essential to unravel the multidimensional nature of caregiver burden and its variations across diverse cultural settings., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Increased time from symptom onset to puncture (TSOP) and time from puncture to reperfusion (TPTR) are associated with worse outcome in ischemic stroke patients treated with endovascular therapy (EVT) in the early time window (<6 h). However, these associations are less described in the late window (>6 h), where patients may benefit from EVT because of a more favorable imaging profile (late window paradox). We sought to compare the effect of these timeframes between these two periods on efficacy and safety outcomes., Methods: The ETIS (Endovascular Treatment in Ischemic Stroke) registry is an ongoing, prospective, observational study in 21 centers that perform EVT in France. We included adult patients with an anterior occlusion, successfully treated by EVT (modified treatment in cerebral ischemia (mTICI) 2b-3) between January 2015 and June 2023, with a known time of stroke onset. The cohort was divided into two groups according to the TSOP (⩽6 h vs >6 h). Primary outcome was favorable outcome (modified Rankin Scale 0-2 at 90 days)., Results: In total, 7516 patients were included, with 5936 patients being treated ⩽6 h and 1580 >6 h. In the early window, TSOP and TPTR were associated with worse outcomes at 90 days (adjusted odds ratio (aOR) = 0.68 per hour; 95% confidence interval (CI) = 0.64-0.73; p  < 0.001 and aOR = 0.92 per 10-min increment; 95% CI = 0.90-0.94, p  < 0.001, respectively). TSOP was not associated with worse outcomes at 90 days in the late window ( p  = 0.955), but TPTR was associated with worse outcomes (aOR = 0.91 per 10-min increment; 95% CI = 0.86-0.96, p  = 0.001), every 10 additional minutes in TPTR being associated with a 1.7% (95% CI = 0.6-2.7) decreased probability of favorable outcome., Conclusion: Only EVT procedural time is associated with unfavorable outcomes at 90 days in late window patients. These results highlight how the late window paradox may end at the start of EVT and underscore the need for timely management, particularly for the EVT, even for late window patients with a presumed more favorable imaging profile., Competing Interests: Declaration of conflicting interestThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: J.-M.O. declares consulting activities with Abbvie, Acticor, and Bioxodes; speaking fees from BMS, Boerhinger Ingelheim; S.F. is the author of a patent (US20200085454A1). B.G. has received grants from the French Ministry of Health and is the primary investigator of the TITAN, DIRECT ANGIO, and IA-RESCUE trial, and consulting fees from Air Liquide, MIVI, Medtronic, Microvention, and Penumbra. M.M. declares consulting fees from Boerhinger Ingelheim, Air Liquide, Acticor Biotech, and Amgen. S.R. declares contracts from Boerhinger Ingelheim France, Bristol-Myers Squibb, and Pfizer SAS.

Estrogen exposure during menstrual years has been associated with late-life neuroprotection. We explored the presence of an age-sensitive menarche window for cognition in old age and the impact of socioeconomic status and education. We compared neuropsychological performance of 1082 older women [Mean AGE = 72.69 (5.48)] with menarche in childhood, early-, mid-, and late-adolescence and dementia prevalence, severity, and type, including the effects of education and socioeconomic status. Adjusting for covariates, menarche at 11-14 years of age was associated with better memory, executive and global cognitive functioning in old age, and stronger positive effects of education and socioeconomic status on cognition than those with menarche at 15-17 years. We found a critical age window for the neuroprotective effects of estrogens during early adolescence, putting women with later menarche at higher risk for cognitive decline. Effects of socioeconomic status and education in adulthood should be a focus of future research.

Research on doping prevention has proliferated in recent years as evidenced by the development of several anti-doping interventions. However, researchers have rarely examined whether an anti-doping intervention delivered and evaluated in one population is similarly effective in a different population. The purpose of our research was to determine whether the psychological intervention developed by Kavussanu et al. (2022) and originally delivered in British and Greek athletes, was equally effective as a standard educational intervention in preventing doping (i.e., by influencing our primary and secondary outcomes) in young Italian athletes. Eligible participants were identified via a screening survey administered to 540 athletes from 46 clubs in Italy. A total of 15 sport clubs (121 athletes; 16.95 % female; aged 18.52 ± 2.15 years) were assigned to one of three conditions: a psychological intervention, an educational intervention, or a no-intervention control group. Each intervention consisted of six 1-h sessions delivered to small groups of athletes over six weeks. Athletes completed measures of doping likelihood, anticipated guilt, moral disengagement, and self-regulatory efficacy pre-intervention, post-intervention, and two months later. Control group participants completed the same measures at the same time points. The two interventions were similarly effective in reducing doping likelihood and increasing anticipated guilt from pre to post, while the control group showed no change; these effects were maintained at follow up. Both interventions reduced moral disengagement and increased self-regulatory efficacy from pre to post relative to the control group, and these effects were maintained at follow-up. In conclusion, our study broadly replicates previous findings and highlights the need for anti-doping organizations to target psychological variables and doping-relevant information in anti-doping education., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Introduction/aims: Risdiplam was the first orally administered drug approved to treat spinal muscular atrophy (SMA). Efficacy in adults is based on short-term observational studies. This longitudinal study aimed to examine risdiplam's efficacy and safety in adults over a long period of follow-up., Methods: All eligible SMA patients ≥ 16 years old, followed at the Muscular Dystrophy Association Hellas Neuromuscular Diseases Unit between April 2021 and December 2023, were included. We prospectively evaluated motor function, muscle strength, and pulmonary function before and after 6, 12, 18, 24, and 30 months of treatment. Laboratory assessments and patient-reported adverse events were recorded., Results: Overall, 14 patients (18-57 years, 93% treatment-naive) received risdiplam for a median period of 28.5 months (range 6-30). There were statistically significant improvements in the Hammersmith Functional Motor Scale-Expanded (mean difference [MD] 1.5 [95%CI 0.49-2.42]), Revised Upper Limb Module (MD 1.6 [95%CI 0.54-2.73]), Motor Function Measurement-32 (MD 2.7[95%CI 1.52-3.93]), Medical Research Council scores of the upper (MD 3 [95%CI 0.8-5.2]), and lower (MD 1.7 [95%CI 0.1-3.3]) limbs (all p ≤ 0.05). Eighty-two percent of patients achieved a clinically meaningful improvement (CMI) in at least one scale. Overall, CMI occurred earlier in type 3 patients. SMA functional rating scale and respiratory function tests remained stable over time. Fifty-seven percent of patients did not report any adverse events. None discontinued treatment., Discussion: Risdiplam treatment over 30 months resulted in overall CMI in most treated adult SMA type 2 or 3 patients. Outpatient drug administration and overall patient management proved feasible and safe. Larger studies are warranted., (© 2024 The Author(s). Muscle & Nerve published by Wiley Periodicals LLC.)

In the realm of epidemiology, it is essential to accurately assess epidemic phenomena through the adoption of innovative techniques that yield reliable predictions. This article introduces an advanced method that merges the Extended Kalman Filter approach with recursive algorithms to compute critical stochastic attributes important for evaluating epidemics. A new three-dimensional discrete Markov chain is presented, according to which the total number of infections, deaths, and the duration of epidemic outbreaks are estimated. This approach represents a notable improvement over the standard estimation procedure, which relies on Markov-based stochastic models with fixed parameters. Furthermore, it constitutes a real-time estimation process, as opposed to the standard method, which is more suitable for offline applications. The proposed methodology marks an original attempt to integrate computational techniques for modeling stochastic epidemic characteristics with dynamic parameter estimation procedures. An additional advantage is the reduction of noise in the system's states enhancing the overall precision. The method's performance is thoroughly assessed through 3 simulated epidemic instances. Furthermore, its application to the actual 2022 monkeypox (mpox) data from the Czech Republic demonstrates promising effectiveness. In comparison to the standard methodology, our approach yields estimates with deviations of only 4.383 weeks, 3.542 infections, and 0.266 deaths, as opposed to the standard method where we observe deviations of 15.372 weeks, 5.786 infections, and 0.501 deaths. Overall, the proposed estimation procedure proves to be a valuable tool for investigating epidemic phenomena characterized by fluctuating dynamics, potentially providing valuable insights for addressing the associated public health challenges. MSC: 62M20, 60J22, 65C40, 62G30, 62P10., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: The impact of obesity on outcomes after adrenalectomy for pheochromocytoma is unclear. This study aims to evaluate outcomes after minimally invasive and open adrenalectomy for pheochromocytoma in patients with obesity and to determine factors that may affect outcomes. Patients undergoing adrenalectomy for pheochromocytoma in 46 international centers between 2012 and 2022 were reviewed, analyzing baseline information, length of hospital stay (LOS), and postoperative complications., Patients and Methods: Obese (body mass index (BMI) ≥ 30 kg/m 2 ) and nonobese patients were compared. Multivariable analysis was utilized to evaluate outcomes and risk factors for complications, LOS, and increased comprehensive complication index (CCI)., Results: Of the 2016 patients, 639 (31.7%) had obesity. Operative time (110.0 versus 105.0 min; p = 0.467), conversion to open rate (3.1% versus 4.7%; p = 0.079), estimated blood loss (20.0 versus 20.0 ml, p = 0.088), rate of complications (19.3% versus 20.8%; p = 0.425), and CCI were similar. However, patients with obesity required a median of 1 day longer LOS (4.0 days versus 5.0 days; p < 0.001). On multivariable analysis, obesity was not significantly associated with complications or higher CCI. Analyzing solely obese patients, laparoscopic (OR 0.24; p < 0.001) and robotic (OR 0.22; p = 0.011) approaches were independently associated with less morbidity. Additionally, multivariable modeling demonstrated that a retroperitoneal approach in patients with BMI ≥ 30 kg/m 2 was independently associated with reduced CCI (- 3.74; p = 0.017). Similar results were demonstrated when analyzing severe obesity (BMI ≥ 35)., Conclusions: Obesity does not increase complications or CCI following pheochromocytoma resection, but it does increase LOS. A retroperitoneal approach may uniquely benefit patients with obesity. In view of rising obesity rates, these results warrant further research to validate findings., Competing Interests: Disclosure: The authors declare no conflicts of interest. Ethical approval: The study was approved with registration: CARMS-18769., (© 2024. Society of Surgical Oncology.)

Background and Aims: While glucagon-like peptide-1 receptor agonists (GLP-1RAs) effectively reduce body weight, their impact on lean mass remains uncertain. This meta-analysis evaluated the effects of GLP-1RAs and GLP-1/GIP receptor dual agonists (GLP-1/GIP-RAs) on body composition, focusing on total weight, fat mass, and lean mass in adults with diabetes and/or overweight/obesity., Methods: A systematic search of Medline, Embase, and the Cochrane Library was conducted through November 12, 2024. Data were analyzed using random-effects pairwise and network meta-analyses to compare interventions with placebo or active comparators., Results: Twenty-two randomized controlled trials (2258 participants) were included. GLP-1RAs significantly reduced total body weight (MD -3.55 kg, 95 %-CI [-4.81, -2.29]), fat mass (MD -2.95 kg, 95 %-CI [-4.11, -1.79]), and lean mass (MD -0.86 kg, 95 %-CI [-1.30, -0.42]), with lean mass loss comprising approximately 25 % of the total weight loss. However, the relative lean mass, defined as percentage change from baseline, was unaffected. Liraglutide, at 3.0 mg weekly or 1.8 mg daily, was the only GLP-1RA to achieve significant weight reduction without significantly reducing lean mass. Tirzepatide (15 mg weekly) and semaglutide (2.4 mg weekly) were the most effective for weight and fat mass reduction but were among the least effective in preserving lean mass., Conclusions: Potent GLP-1 RAs, such as tirzepatide and semaglutide, demonstrate greater overall weight loss but are associated with a significant reduction in lean mass., Competing Interests: Declaration of competing interest CSM reports grants through his institution from Merck, Esperion, Abbott, Massachusetts Life Sciences Center and Boehringer Ingelheim, has received personal consulting fees and support with research reagents from Ansh Inc., collaborative research support from LabCorp Inc., reports personal consulting fees from Olympus, Genfit, Lumos, Novo Nordisk, Amgen, Corcept, Intercept, 89 Bio, Madrigal, Aligos, Esperion and Regeneron, reports educational activity meals through his institution or national conferences from Esperion, Merck, Boehringer Ingelheim and travel support and fees from UpToDate, TMIOA, Elsevier, and the Cardio Metabolic Health Conference. None is related to this paper. CSM recused himself from handling this paper. The rest authors declare no conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background and Aims: Liver-related complications are frequent in patients with metabolic diseases, with limited treatment options currently available. This systematic review and meta-analysis aimed to assess the effect of fibroblast growth factor-21 (FGF21) analogues on hepatic steatosis, inflammation and fibrosis in patients with metabolic diseases., Methods: We conducted a systematic literature search in Pubmed, Scopus and Web of Science for randomised controlled trials (RCTs) assessing the effect of FGF21 analogues on hepatic steatosis evaluated by hepatic fat fraction (HFF), inflammation and fibrosis compared to placebo. Adverse events (AEs) were also recorded., Results: Treatment with FGF21 analogues was associated with metabolic-associated steatohepatitis (MASH) resolution without fibrosis worsening (5 studies, risk ratio [RR] 4.40, 95% confidence interval [CI]: 2.41, 8.03, p < 0.001) and fibrosis improvement by 1 grade without MASH worsening (6 studies, RR 1.79, 95% CI: 1.24, 2.59, p = 0.002). FGF21 analogues significantly lowered HFF compared to placebo (6 studies, SMD -1.08, 95% CI: -1.28, -0.88, p < 0.001), while patients receiving FGF21 analogues were more likely to exhibit a reduction in HFF by 30% (10 studies, RR 4.08, 95% CI: 3.08, 5.40, p < 0.001) or 50% (6 studies, RR 10.43, 95% CI: 5.47, 19.87, p < 0.001). HFF normalisation (≤ 5%) was more frequently achieved with FGF21 analogues (6 studies, RR 14.58, 95% CI: 4.70, 45.18, p < 0.001). The results remained robust after sensitivity analyses. Serious AE and AE leading to drug discontinuation were similar in patients receiving FGF21 analogues or placebo., Conclusions: FGF21 analogues can reduce hepatic steatosis, inflammation and fibrosis in patients with metabolic diseases, representing a possible treatment option for steatotic liver disease., (© 2025 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objectives: The aim of the present study was to assess the reliability of aponeurosis and muscle thickness of the hamstrings using ultrasound (US)., Methods: US images were captured from the semitendinosus (ST) and biceps femoris long head (BFlh) of 30 individuals (15 females), undergoing two testing sessions with a 24-hour interval. Measurements were taken at six sites along the thigh at two knee angles (0° = full extension and 90°) in prone position. Aponeurosis and muscle thickness across the entire length of ST and BFlh were evaluated using computational image segmentation which generated ~360 data points per participant., Results: The intraclass correlation coefficients ranged from 0.937 to 0.998 while the standard error of measurement varied from 0.88 to 2.72% for superficial aponeurosis, from 1.41 to 2.29% for deep aponeurosis, and from 1.50 to 4.22% for muscle thickness. The minimal detectable change ranged from 2.44 to 7.56% for the superficial aponeurosis, from 3.57 to 6.27% for deep aponeurosis, and from 4.17 to 11.70% for BF and ST muscle thickness., Conclusions: Evaluation of hamstring aponeurosis and muscle thickness measurements at rest displayed very high reliability and, hence, such measurements can be used to diagnose changes in thickness due to injury or exercise interventions., (© 2024 The Author(s). Journal of Ultrasound in Medicine published by Wiley Periodicals LLC on behalf of American Institute of Ultrasound in Medicine.)

Heart failure (HF) is a major clinical challenge characterized by significant morbidity and mortality. Electrical conduction abnormalities play a critical role in HF pathophysiology and progression, often leading to suboptimal outcomes with conventional pacing techniques. Con-duction system pacing (CSP), encompassing His bundle pacing and left bundle branch area pacing, has emerged as a novel approach. Despite data come from observational studies, recent guidelines recommend that a specific population may benefit from CSP. However, significant practical considerations and challenges need to be clarified before CSP can be routinely implemented in clinical practice. The reliance on observational studies means that long-term clinical outcomes for HF patients remain uncertain until data from randomized controlled trials (RCTs) become available. Current CSP practices face challenges with lead implantation, mechanical stress on leads, and the need for more advanced tools and artificial intelligence integration to improve procedure efficacy and safety. Future large-scale RCTs are essential to identify optimal candidates and address these technical challenges, potentially leading to a paradigm shift in HF management., Competing Interests: Declarations. Ethical approval: Ethical approval is not applicable as the current paper is review. Competing interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: The assessment of gait disorders in patients with neuromotor conditions, such as cerebral palsy (CP), has been a focus of clinical and research attention, with electromyography (EMG) offering a nuanced understanding of neurological and neuromuscular disorders. However, the interpretation of EMG data in the context of gait analysis remains challenging due to the complexity of neuromotor dynamics and variability in assessment methodologies., Research Question: To which consensus can we get in a group of experts in the fields of neurological and neuromuscular disorders, biomechanics, and clinical gait analysis to establish standardized protocols and a common language for the measurement and analysis of EMG data in gait disorders, particularly in people living with CP?, Methods: A three-round Delphi process was conducted from February to September 2023 to gather opinions of 53 experts on the use of surface EMG data during gait in the context of CP. The surveys were conducted using the tool 'SoSci Survey' with a focus on free-text answers., Results: The experts agreed on the usefulness of EMG data, but a consensus on specific clinical decisions involving EMG could not be reached. Additionally, the study provides a terminological framework for EMG evaluation during gait and a comprehensive list of practical problems and solutions, when evaluating EMG data. The study indicates that, despite a general community consensus on the ideal approaches to data processing and evaluation, these methods are not commonly implemented in a standardized manner. Both raw and enveloped data are widely used in clinical routines, however, the protocol for generating normative data lacks consistency across gait laboratories., Significance: The study suggests that while there may be differences in the way EMG data is analyzed, there is a shared understanding of the key features that are relevant for gait analysis., Competing Interests: Declaration of Competing Interest “Each of the authors has read and concurs with the content in the final manuscript. The material within has not been and will not be submitted for publication elsewhere except as an abstract." There is no conflict of interests., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

In this study, the removal of sulfadoxine (SDX) with the electro-Fenton (EF) process is for the first time investigated, in a commercially available filter press electrochemical cell. A Gas Diffusion Electrode (GDE) was used as the cathode and a Dimensionally Stable Anode (DSA) as the anode. The effects of current density, recirculation flow, and pH on H 2 O 2 generation were examined. The maximum H 2 O 2 concentration was 457 mg/L at 50 mA/cm 2 , 200 mL/min, and pH 7 after 2 h of operation. Under the same conditions, the effect of Fe 2+ on SDX oxidation and mineralization was studied. With 0.5 mM Fe 2+ , SDX was eliminated within 10 min, with 77.4% total organic carbon (TOC) removal after 2 h. Notably, Fe precipitation was observed at near-neutral pH, indicating that removal via coagulation and adsorption may have contributed to SDX elimination in addition to oxidation. Five transformation products (TPs) were identified via LC/HRMS Orbitrap, with four newly reported. The acute and chronic toxicity of the TPs was assessed in fish, daphnia, and green algae using ECOSAR software. Most TPs showed lower toxicity than SDX, though some exhibited increased toxicity, suggesting longer or more intense treatments may be needed. The stability of the GDE was evaluated over 10 consecutive cycles with 0.1 mM Fe 2+ . SDX removal remained stable, ranging from 72.2% to 85.4%, though H 2 O 2 electrogeneration decreased steadily from 481.4 mg/L to 200.6 mg/L by the final cycle. These results suggest that while EF effectively removes SDX, improvements in H 2 O 2 generation stability are necessary for long-term use., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025. Published by Elsevier Ltd.)