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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.)

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.)

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.)

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: 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.)

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.)

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.)

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: 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.)

Background: Brain organoids have emerged as powerful models for studying brain development and neurological disorders COMPARISON WITH EXISTING METHODS: Current models rely on stem cell isolation and differentiation using different growth factors. Thus, their composition varies according to the protocol followed., New Method: We developed a simple protocol to generate organoids from newborn rat whole brain. It is a one-step procedure that yields organoids of consistent composition. The whole brains from 3-day old pups were digested enzymatically. All isolated cells were seeded in culture plates using a basement membrane extract (BME) matrix as a scaffold and cultured in the presence of the appropriate medium., Results: Hematoxylin-eosin staining of 28-day-old cultured domes revealed their structural integrity, while immunohistochemistry confirmed the presence of neurons, astrocytes, microglia, and progenitor stem cells in the structures. To assess whether these organoids can serve as a model to study brain physiopathology, and in particular neurodegenerative diseases such as Alzheimer's disease (AD), we determined how these organoids respond upon their exposure to lipopolysaccharides (LPS), a potent neuroinflammatory factor. LPS-induced amyloid precursor protein (APP), tau protein and glial fibrillary acidic protein (GFAP) expression. Moreover, the intracellular levels of IL-1β and the extracellular levels of amyloid-beta (Aβ) were also elevated., Conclusions: Therefore, this simple protocol results in the generation of functional brain organoids with a consistent structure, that requires no use of varying factors that may affect the structure and function of the produced organoids, thus providing a valuable tool for the study of the physiopathology of neurodegenerative disorders., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest., (Copyright © 2025. Published by Elsevier B.V.)

Objective: In recent years, several questionnaires have been developed to assess the quality of life of patients involved in assisted reproductive treatments, the degree of patient engagement and the outcome of assisted reproductive efforts. This review aimed to evaluate the psychometric properties of the SCREENIVF questionnaire., Methods: Studies were searched in PubMed, Google Scholar, Epistemonikos.org, and PROSPERO up to July 2024. The search resulted in 66 studies, eight of which were eligible to be included in the systematic review. COSMIN guidelines were used for methodological quality assessment of studies and measurement property evaluation. The strength of evidence was rated according to the GRADE approach., Results: SCREENIVF was categorized as stage A for "internal consistency" (Cronbach's >0.7), "structural validity", "discriminant" and "convergent" validity. Reliability was categorized as stage A in couples [ICC (Intraclass Correlation Coefficient) >0.7], while its use exclusively in women is contraindicated. Concerning "cross-cultural validity" and "criterion validity", it was categorized as stage B and is recommended for use when no stage A questionnaires are available. Cross-cultural validity was deemed questionable as none of the studies performed Differential Item Functioning Analyses [DIF]., Conclusion: This systematic review highlights the importance of adopting standardized procedures for assessing the psychometric properties of questionnaires used in assisted reproduction., 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.)

Promoting the highest quality, evidence-based research across Europe is a priority of the European Stroke Organisation (ESO). The ESO Guideline Board communicate and promote evidence-based recommendations for clinical practice through their Guidelines. However, there are many aspects of stroke care where robust scientific evidence may be unavailable or difficult to obtain. Thus, there is a need for practical, consensus guidance, produced following robust, consistent, and transparent methods, that is suitable for high-priority clinical scenarios where evidence is currently lacking. The ESO Guideline Board developed methods for producing practical clinical guidance based on expert consensus in response to this need. These ESO' White Papers' are intended to complement standard ESO Guidelines. Here, we outline the ESO White Papers' standard operating procedure (SOP). We will describe the motivation for creating White Papers, the preferred composition of writing groups and expert consensus panellists, the methods for achieving consensus, and how results will be communicated. To ensure that all voting members have an equal voice, our methods are based upon the Delphi process of repeated rounds of anonymous voting, feedback and review. We hope that the White Papers will add further value to the clinical practice guidance that is offered by ESO. We look forward to receiving suggestions for White Paper topics from the stroke community., Competing Interests: Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: TQ has received funding from NIHR for methodology work around guidelines and evidence synthesis. JCP has received consultation fees and travel expenses from Abbott, Akcea, Bayer, Boehringer Ingelheim, Daiichi Sankyo, and Pfizer, outside the submitted work. SP received research support from BMS/Pfizer, Boehringer-Ingelheim, Daiichi Sankyo, DOASENSE, European Union, German Federal Joint Committee Innovation Fund, and German Federal Ministry of Education and Research, Helena Laboratories and Werfen as well as speakers’ honoraria/consulting fees from Alexion, AstraZeneca, Bayer, Boehringer-Ingelheim, BMS/Pfizer, Daiichi Sankyo, Portola, and Werfen (all outside the submitted work). DS has received funding from: Advisory Board: Astra-Zeneca, Alexion, CSL Behring, Shionogi, BMS, Janssen. Unrestricted Research or Educational Grants: Boehringer-Ingelheim. DAdS reports grants from the Portuguese Foundation for Science and Technology, MSD and ESR, advisory board participation for Bayer, Johnson & Johnson and Daiichi-Sankyo, and speaker fees from Bial and Astrazeneca.

Background : The purpose of this study was to detect proteomic alterations and corresponding signaling pathways involved in the formation of age-related cataract (ARC), diabetic cataract (DC), and post-vitrectomy cataract (PVC). Methods : Three sample types, the aqueous humor (AH), the anterior capsule (AC), and the content of the phaco cassette, were collected during phacoemulsification surgery. The samples were obtained from 12 participants without diabetes mellitus (DM), 11 participants with DM, and 7 participants without DM, with a history of vitrectomy surgery in the past 12 months. The Sp3 protocol (Single-Pot, Solid-Phase, Sample-Preparation) was used for the sample preparation. The recognition and quantification of proteins were carried out with liquid chromatography online with tandem mass spectrometry. The DIA-NN software was applied for the identification and quantification of peptides/proteins. Statistical analysis and data visualization were conducted on Perseus software. Data are available via ProteomeXchange. Results : A very rich atlas of the lens and AH proteome has been generated. Glycosaminoglycan biosynthesis and the non-canonical Wnt receptor signaling pathway were differentially expressed in ARC compared to both the DC and PVC groups. In the PVC group, complement activation was differentially expressed in AH samples, while glutathione metabolism and oxidoreductase activity were differentially expressed in AC samples. Microfilament motor activity, microtubule cytoskeleton organization, and microtubule binding were differentially expressed in the DC and PVC groups in both AH and AC samples. Conclusions : The results of this study expand the existing knowledge on pathways involved in the pathophysiology of cataract, and suggest possible important druggable targets for slower progression or even prevention of cataract.

Introduction: Cervical pregnancy is a rare kind of ectopic pregnancy. Heterotopic pregnancy is a condition, where we have one sac in the uterus and one in another location, usually because of IVF treatment. This scenario can become a life-threatening condition, if remain untreated., Presentation of Case: A 44-year-old woman underwent IVF (egg donation) with double embryotransfer and resulted in twin pregnancy, however heterotopic. One in cervix and one intrauterine. Until 8 weeks both pregnancies evoluting equally and then a decision made to terminate the cervical one. Her physician chose a transabdominal approach (amniocentesis wise); however, this attempt failed. Then, intracervical puncture by a reproductive specialist was attempted with potassium chloride injection and aspiration of the amniotic fluid. The pregnancy was terminated successfully, and no complications presented afterwards. The intrauterine pregnancy evoluted normally and a livebirth was achieved at 39 weeks., Discussion: The current case represents an interesting way of terminating a cervical pregnancy even in the presence of a twin intrauterine sibling., Conclusion: Patients with heterotopic pregnancies, should be encouraged not to terminate both pregnancies and to be referred in specialized reproductive and fetal maternity centers., Competing Interests: Conflict of interest statement None., (Copyright © 2025 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Aim: To provide normative data for the lateralization task in the assessment of intranasal trigeminal function, as well as to investigate potential effects of age, sex and olfactory function., Methods: The lateralization task using eucalyptus as target stimulus was performed to assess intranasal trigeminal function. Data were collected from: 360 healthy adult participants (mean age 37.5 ± 17.4) for the 40-trial version; 284 participants (mean age 32.6 ± 4.1) for the 20-trial version; and 418 participants (mean age 42.6 ± 15.6) for the 10-trial version. The "Sniffin Sticks" test was used to measure olfactory function., Results: The mean scores were 35.46 ± 4.50 for the 40-trial version, 15.64 ± 3.65 for the 20-trial version, and 8.14 ± 2.16 for the 10-trial version. In the reference group aged 18-25 years, the 10th percentiles were 33 for the 40-trial version, 11 for the 20-trial version, and 6 for the 10-trial version. Significant effects of age and odor discrimination score were observed on lateralization performance., Conclusions: We provide reference scores for the lateralization task, in large sample of healthy participants. Among the three examined tasks (40, 20 and 10), the 40-trial task yielded the most reliable information. For the 40-trial version, scores equal or higher to 33 points indicate a normal lateralization ability, whereas scores between 27 and 32 may warrant further assessment. Scores below 27 possibly point towards a decreased trigeminal function. The lateralization task serves as surrogate marker of intranasal trigeminal functions and further studies with pathological cases are needed to explore its clinical usefulness.

Background: Dermoscopy is a valuable tool in the diagnosis of various skin conditions. It increases sensitivity and specificity in skin cancer diagnosis, as well as in infectious, inflammatory and hair diseases. However, mastering the intricacies of dermoscopy can be challenging. In this context, innovative educational methods are sought, including game-based learning (GBL) strategies., Objectives: To describe current perceptions, knowledge and use of GBL strategies in dermoscopy education, and identify strengths and challenges to enhance their use., Methods: A web-based cross-sectional survey with 25 questions was distributed to members of the International Dermoscopy Society -between October 2022 and April 2023. Responses were collected and analysed using frequency analysis and graphical representation., Results: In total, 801 responses were received. Of these, 46.6% of respondents were unfamiliar with gamification and serious games. Among those acquainted with these concepts, 56.3% reported using GBL strategies for education. Younger participants were more likely to use GBL strategies (P = 0.02). Participants familiar with GBL believed it enhanced medical education (78.5%) but should not entirely replace traditional teaching methods (96.0%). For dermoscopy education specifically, 22.1% of respondents had used GBL strategies, with Kahoot! (35.5%) and YOUdermoscopy (24.1%) being the most commonly used platforms. Respondents found gaming strategies to be fun (95.5%), motivating (91.0%) and valuable for e-learning (94.4%)., Conclusions: Results from this survey demonstrate a favourable perception of GBL strategies in dermatology education, including dermoscopy. While there are ongoing challenges in validation, GBL strategies are promising and valuable tools that can aid the learning and teaching experience. Addressing implementation barriers and validating existing games could optimize the impact of GBL on dermatology education., Competing Interests: Conflicts of interest: The authors declare no conflicts of interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Association of Dermatologists. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

The spread of NDM-1-harboring Klebsiella pneumoniae is a worldwide concern. In this study the whole-genome sequence (WGS) of a carbapenem- and colistin-resistant K. pneumoniae 838Gr strain is presented. This strain was isolated from a urine sample of a patient in the Intensive Care Unit (ICU) at Volos Hospital, Greece. The initial assembly produced 224 contigs with a combined genome size of 5,561,803 bp and a GC content of 57.21%. The K. pneumoniae strain carried IncR, IncFIA, IncC, and repB (R1701) replicons. Multilocus sequence typing (MLST) analysis revealed that the isolate belonged to the sequence type 11 (ST11) and serogroup KL24 and O2a. The WGS analysis identified several beta-lactamase genes (blaTEM-1B, blaCTX-M-15, blaNDM-1, blaOXA-1, blaVEB-1, blaOXA-10, and blaSHV-11) alongside resistance genes for other antibiotic classes, including floR2, cmlA1, cmlA5, catB3, arr-3, aph(6)-Id, aadA2. Colistin resistance was attributed to specific point mutations in pmrB (R256G, T140P). This is the first report of a carbapenem- and colistin-resistant K. pneumoniae ST11 strain in Greece. The findings of this study highlight the urgent need for increased surveillance and stringent infection control.

Prcis: In 801 participants, corneal hysteresis (CH) was positively associated with female gender and central corneal thickness, and negatively with age and axial length. Diabetes showed no significant association with CH in the adjusted models., Purpose: To provide values of corneal hysteresis (CH) in an elderly, healthy Greek population and to investigate its association with demographic, ocular, and systemic factors., Methods: Cross-sectional population-based study. Out of 1,092 participants in the incidence cohort of the Thessaloniki Eye Study (TES) who were re-examined between 2013 and 2015, there were 801 eligible subjects in this study according to pre-specified criteria. All subjects underwent an interview and a comprehensive clinical examination. Demographic data and medical and ophthalmic, family, and smoking histories were recorded. CH was evaluated with Ocular Response Analyzer (ORA)., Results: The mean age of study subjects was 79.7±3.9 years and 345 out of 801 participants (43.1%) were female. The mean CH among all subjects was 10.1±1.5 mmHg. After adjusting for age, gender, central corneal thickness (CCT), axial length (AL), and diabetes, CH was positively associated with female gender (β=0.446; P<0.0001) and CCT (β=0.017; P<0.0001), and negatively associated with age (β=-0.024; P=0.038) and AL (β=-0.181; P<0.0001). There was no association between CH and diabetes (β=0.186; P=0.10). In a supplementary multivariable analysis of a smaller sample size, where we included corneal curvature (CC) as an additional covariate, no association was found between CH and CC (β=-0.235; P=0.26) or age (β=-0.023; P=0.09)., Conclusion: This study outlined variations in CH among a Greek population. CH decreased with advancing age while women had greater CH compared to men. In addition, eyes with thinner corneas and longer AL had lower CH values. No significant associations were found between CH and CC or the presence of diabetes., (Copyright © 2025 Wolters Kluwer Health, Inc. All rights reserved.)

Elucidating how protein sequence determines the properties of disordered proteins and their phase-separated condensates is a great challenge in computational chemistry, biology, and biophysics. Quantitative molecular dynamics simulations and derived free energy values can in principle capture how a sequence encodes the chemical and biological properties of a protein. These calculations are, however, computationally demanding, even after reducing the representation by coarse-graining; exploring the large spaces of potentially relevant sequences remains a formidable task. We employ an "active learning" scheme introduced by Yang et al. ( bioRxiv , 2022, https://doi.org/10.1101/2022.08.05.502972) to reduce the number of labelled examples needed from simulations, where a neural network-based model suggests the most useful examples for the next training cycle. Applying this Bayesian optimisation framework, we determine properties of protein sequences with coarse-grained molecular dynamics, which enables the network to establish sequence-property relationships for disordered proteins and their self-interactions and their interactions in phase-separated condensates. We show how iterative training with second virial coefficients derived from the simulations of disordered protein sequences leads to a rapid improvement in predicting peptide self-interactions. We employ this Bayesian approach to efficiently search for new sequences that bind to condensates of the disordered C-terminal domain (CTD) of RNA Polymerase II, by simulating molecular recognition of peptides to phase-separated condensates in coarse-grained molecular dynamics. By searching for protein sequences which prefer to self-interact rather than interact with another protein sequence we are able to shape the morphology of protein condensates and design multiphasic protein condensates.

Background: Changes in retinal vessel caliber are crucial for detecting early retinopathy, a significant cause of blindness in individuals with Diabetes Mellitus type 2 (T2DM). This study aims to evaluate the changes in retinal vessel caliber and identify factors associated with these changes in recently diagnosed T2DM patients., Methods: The study included newly diagnosed T2DM patients (within 6 months of diagnosis) who were free of antidiabetic treatment (except metformin) and matched individuals based on age and blood pressure (BP). Data collected included somatometric measurements, BP (office and 24-hour), hematological data, albuminuria (via 24-hour urine collections), ten-year atherosclerotic cardiovascular disease risk (ASCVD score), endothelial dysfunction (measured by Asymmetric Dimethylarginine, ADMA), retinal microvascular changes, assessed as central retinal arteriolar equivalent (CRAE), central retinal venular equivalent (CRVE), and arteriovenous ratio (AVR) using specialized software on non-mydriatic fundus photographs., Results: The study involved 87 T2DM patients and 90 controls, aged 57±11 years. Key findings include no significant differences in CRAE, CRVE, and AVR between T2DM patients and controls. Age (p=0.019) and nighttime systolic BP (SBP) (p=0.002) were independent predictors of AVR. CRAE was independently associated with nighttime SBP (p=0.048). CRVE was independently associated with age (p=0.016), dipping (p=0.002), and smoking (p=0.018). In normotensive subjects, AVR was significantly lower in T2DM patients (p=0.035)., Conclusions: The study concludes that increased nighttime SBP is a more critical factor than hyperglycemia in affecting retinal vascular caliber changes in newly diagnosed T2DM patients. This highlights the importance of managing nocturnal hypertension to prevent retinal damage in this patient population., (© The Author(s) 2025. Published by Oxford University Press on behalf of American Journal of Hypertension, Ltd.)

The current case report presents the postmortem examination findings of a 17-week-old female fetus displaying thanatophoric dysplasia type 1 (TD-1) due to a known fibroblast growth factor receptor 3 (FGFR3) gene mutation. Gross and X-ray examination revealed significant abnormalities, including skeletal malformations with prominent TD-1 femur curvature. Microscopical evaluation indicated inadequate histological growth for the gestational age, with specific organ immaturity noted in multiple hematoxylin and eosin sections from internal organs, bone from epiphyses and diaphyses levels. Immunohistochemical analysis was conducted using specific markers, such as S100, CD34, CD117, glycophorin-C, and myeloperoxidase, to identify various hematopoietic and mesenchymal cell types. Furthermore, this report underscores the often-overlooked aspect of fetal hematopoiesis in cases diagnosed with TD-1, shedding light on the development of hematopoietic cells and their markers in various tissues, with a particular emphasis on the investigation of bone marrow foci in areas with incipient or no apparent ossification. Immunohistochemical identification of hematopoiesis also served as an indirect way to identify areas of incipient or abnormal ossification., (© 2025 The Author(s). Congenital Anomalies published by John Wiley & Sons Australia, Ltd on behalf of Japanese Teratology Society.)

Background: Patients with COPD frequently demonstrate pulmonary hypertension (PH). Severe PH in patients with COPD, identified by pulmonary vascular resistance (PVR) of > 5 Wood units (WU), is closely linked to impaired transplant-free survival. The impact of PH-targeting pharmacotherapy in this context remains unclear., Research Question: Is PH-targeted therapy associated with improved transplant-free survival in patients with COPD and PH?, Study Design and Methods: This study included Pulmonary Vascular Research Institute GoDeep meta-registry patients with COPD and PH and available right heart catheterization at diagnosis. We investigated PH-targeted therapy prevalence and its association with transplant-free survival using diverse statistical methods, including Cox regression and subgroup analyses based on PH severity, comorbidities, and pulmonary function test results. Immortal time bias was addressed through a landmark approach., Results: As of December 2023, the GoDeep meta-registry included 26,981 patients (28% in PH group 1, 13% in PH group 2, 12% in PH group 3, 10% in PH group 4, 2% in PH group 5, 26% undefined, and 9% control participants). Of these, 836 patients had a diagnosis of COPD with PH and were included in this analysis, with median age of 66 years (interquartile range [IQR], 59-73 years), FEV 1 of 51% predicted (IQR, 34%-69% predicted), mPAP of 35 mm Hg (IQR, 28-44 mm Hg), PVR of 5 WU (IQR, 4-8 WU), cardiac index of 2.5 L/min/m 2 (IQR, 2.0-2.9 L/min/m 2 ), and mostly World Health Organization functional class III were included. Five-year transplant-free survival was 42%, significantly worse than in group 1 PH. A multivariable Cox proportional hazards model identified PVR, but not FEV 1 , as a major predictor of outcome. Four hundred eighteen patients (50%) received phosphodiesterase-5 inhibitor (PDE5i) therapy, which was associated with significantly reduced mortality: hazard ratio of 0.65 (IQR, 0.57-0.75) for the entire cohort of patients with COPD and PH and of 0.83 (IQR, 0.74-0.94) when performing landmark analysis. This PDE5i effect was reproduced robustly when performing subgroup analyses for patients with moderate to severe PH, various comorbidities, and supplemental oxygen requirement and when assessing the impact of unobserved confounders., Interpretation: Patients with COPD and PH exhibit poor transplant-free survival, with PVR being a predictor of mortality. In this meta-registry, PDE5i therapy was associated with a significant reduction in mortality across all tested models., Competing Interests: Financial/Nonfinancial Disclosures The authors have reported to CHEST the following: K. T. has received personal fees from Bayer, AstraZeneca, and Gossamer. A. Y. has received personal fees from MSD and support for scientific meetings from AOP. D. G. K. reports support from the Sheffield Biomedical Research Centre and consulting fees and other payments from Jansen Pharmaceuticals, Ferrer, Altavant, MSD, and United therapeutics. H. O. reports grants or contracts from Actelion, Bayer, Boehringer-Ingelheim, Janssen, MSD, IQVIA, and Pfizer; consulting fees from Bayer and IQVIA; speaker fees from Actelion, Bayer, Boehringer-Ingelheim, MSD, and Pfizer; support for scientific meetings from Astra Zeneca, Boehringer-Ingelheim, Menarini, and MSD; and participation on data safety board or advisory board for Bayer and IQVIA. G. K. reports consulting and speaker fees from Boehringer-Ingelheim, Janssen, MSD, Astra Zeneca, Chiesi, AOP, and Ferrer and support for scientific meetings from AOP, Vitalaire, MSD, and Boehringer-Ingelheim. P. M. H. reports personal fees from Merck Co. M. R. W. reports personal fees from MorphogenIX, Janssen, Chiesi, and Aerami; grants from British Heart Foundation and NIHR; and personal fees from MSD, Benevolent AI, and Tiakis Biotech outside the submitted work. L. H. reports personal fees and nonfinancial support from Janssen and personal fees from MSD, Gossamer, and Altavant. M. R. has received support from Janssen Pharmaceutica and Bayer Pharma AG, and speaker fees from Janssen Pharmaceutica and OMT. H.-A. G. has received fees from Actelion, AstraZeneca, Bayer, GSK, Janssen-Cilag, Lilly, Novartis, OMT, Pfizer, and United Therapeutics. W. S. has received consultancy fees from United Therapeutics, Tiakis Biotech AG, Liquidia, Pieris Pharmaceuticals, Abivax, Pfizer, and Medspray BV. None declared (R. W. M., A. L., E. B., J. S. A., A. B., Z. K., A. J. S., R. T. Z., A. A., G. G., H. R. C., R. F., P. G. W., M. Frauendorf, K. M., T. A., M. Feunerich, F. G., J. W.)., (Copyright © 2024. Published by Elsevier Inc.)

The aim of the study was to evaluate the performance of the BCID2 FilmArray panel in relation to blood culture. 162 positive blood cultures were subjected to both classical microbiology methods and the FilmArray nested multiplex PCR. The BCID2 panel showed 96.7% sensitivity, 99% specificity and 99% accuracy., Competing Interests: Declaration of competing interest There is no any conflict of interest, (Copyright © 2024 Elsevier Inc. All rights reserved.)

Regulators worldwide introduce measures to improve energy consumption and reduce greenhouse emissions of road vehicles. The present study focuses on the impacts of passenger car carbon dioxide (CO 2 ) and fuel efficiency measures, attempting to evaluate their effectiveness using vehicle and fleet modelling. To obtain a robust counterfactual result, two regions are compared as a case study: the European Union (EU), where CO 2 emissions have been regulated for over fifteen years, and Australia, a region that recently introduced such a policy element. The average difference in the certified CO 2 emissions of new cars registered in the two regions increased from 50 g/km in 2018 to 60 g/km in 2021 due to accelerated electrification in the EU. To demonstrate the importance of mandatory targets, a sensitivity analysis of the 2020 EU registrations showed that lower by one-third sales of zero and low-emission vehicles (Z-L-EVs) would have resulted in seven out of ten manufacturer pools failing to meet the 2020 target of 95 g/km. The simulation framework was validated against certified values of 2021 registrations and was subsequently used to calculate real-world fleet performance to quantify the actual emissions savings. The real-world CO 2 emissions in the registered fleets for 2021 were estimated to be 143 g/km and 204 g/km, for the EU and Australia, respectively. With these results as a reference, the share of ZEVs required to meet the targets set in both regions is calculated: 51% of the new registrations in 2030 in the EU for achieving 49.5 g/km, and 60% in Australia for recently set target of 58 g/km for 2029. The respective calculated average fleet-wide real-world tailpipe CO 2 emissions were estimated to be 66 g/km (EU) and 77 g/km (Australia). As a last step, the study discusses the application of similar tools and analysis in the design of future policies., 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.)