Miracle-dz/UniFAR-FTUs huggingface dataset:
Sleep spindle maturity promotes slow oscillation-spindle coupling across child and adolescent development

The synchronization of canonical fast sleep spindle activity (12.5–16 Hz, adult-like) precisely during the slow oscillation (0.5–1 Hz) up peak is considered an essential feature of adult non-rapid eye movement sleep. However, there is little knowledge on how this well-known coalescence between slow oscillations and sleep spindles develops. Leveraging individualized detection of single events, we first provide a detailed cross-sectional characterization of age-specific patterns of slow and fast sleep spindles, slow oscillations, and their coupling in children and adolescents aged 5–6, 8–11, and 14–18 years, and an adult sample of 20- to 26-year-olds. Critically, based on this, we then investigated how spindle and slow oscillation maturity substantiate age-related differences in their precise orchestration. While the predominant type of fast spindles was development-specific in that it was still nested in a frequency range below the canonical fast spindle range for the majority of children, the well-known slow oscillation-spindle coupling pattern was evident for sleep spindles in the adult-like canonical fast spindle range in all four age groups—but notably less precise in children. To corroborate these findings, we linked personalized measures of fast spindle maturity, which indicate the similarity between the prevailing development-specific and adult-like canonical fast spindles, and slow oscillation maturity, which reflects the extent to which slow oscillations show frontal dominance, with individual slow oscillation-spindle coupling patterns. Importantly, we found that fast spindle maturity was uniquely associated with enhanced slow oscillation-spindle coupling strength and temporal precision across the four age groups. Taken together, our results suggest that the increasing ability to generate adult-like canonical fast sleep spindles actuates precise slow oscillation-spindle coupling patterns from childhood through adolescence and into young adulthood.
Multicentre, national, investigator-initiated, randomised, parallel-group, register-based superiority trial to compare extended ECG monitoring versus standard ECG monitoring in elderly patients with ischaemic stroke or transient ischaemic attack and the effect on stroke, death and intracerebral blee

Introduction Atrial fibrillation (AF) is a major risk factor for ischaemic stroke and transient ischaemic attack (TIA), and AF detection can be challenged by asymptomatic and paroxysmal presentation. Long-term ECG monitoring after ischaemic stroke or TIA is recommended by all major societies in cardiology and cerebrovascular medicine as a secondary prophylactic measure. However, data on stroke reduction are lacking, and the recommendations show significant diversity. Methods and analysis AF SPICE is a multicentre, national, investigator-initiated, randomised, parallel-group, register-based trial comparing extended ECG monitoring versus standard ECG monitoring in patients admitted with ischaemic stroke or TIA, with a composite endpoint of stroke, all-cause-mortality and intracerebral bleeding. Patients aged ≥70 years without previous AF will be randomised 1:1 to control (standard ECG monitoring) or intervention (extended ECG monitoring). In the control arm, patients will undergo 48±24 hours (ie, a range of 24–72 hours) of continuous ECG monitoring according to national recommendations. In the intervention arm, patients will undergo 14+14 days of continuous ECG monitoring 3 months apart using an ECG patch device, which will provide an easy-accessed, well-tolerated 14-day continuous ECG recording. All ECG patch recordings will be read in a core facility. In cases of AF detection, oral anticoagulation will be recommended if not contraindicated. A pilot phase has been concluded in 2022, which will transcend into the main trial during 2023–2026, including approximately 30 stroke units. The sample size was calculated to be 3262 patients. The primary outcome will be collected from register data during a 36-month follow-up. Ethics and dissemination Ethical approval has been provided by the Swedish Ethical Review Authority, reference 2021–02770. The trial will be conducted according to the ethical principles of the Declaration of Helsinki and national regulatory standards. Positive results from the study have the potential for rapid dissemination in clinical practice. Trial registration number NCT05134454.
Variola Virus and Clade I Mpox Virus Differentially Modulate Cellular Responses Longitudinally in Monocytes During Infection

Abstract Variola virus (VARV), the etiological agent of smallpox, had enormous impacts on global health prior to its eradication. In the absence of global vaccination programs, mpox virus (MPXV) has become a growing public health threat that includes endemic and nonendemic regions across the globe. While human mpox resembles smallpox in clinical presentation, there are considerable knowledge gaps regarding conserved molecular pathogenesis between these 2 orthopoxviruses. Thus, we sought to compare MPXV and VARV infections in human monocytes through kinome analysis. We performed a longitudinal analysis of host cellular responses to VARV infection in human monocytes as well as a comparative analysis to clade I MPXV-mediated responses. While both viruses elicited strong activation of cell responses early during infection as compared to later time points, several key differences in cell signaling events were identified and validated. These observations will help in the design and development of panorthopoxvirus therapeutics.
Discovering KYNU as a feature gene in hidradenitis suppurativa

Background Hidradenitis suppurativa (HS) is a chronic auto-inflammatory skin condition characterized by nodules, abscesses, and fistulae in skin folds. The underlying pathogenesis of HS remains unclear, and effective therapeutic drugs are limited. Methods We acquired mRNA expression profiles from the Gene Expression Omnibus (GEO) database and conducted differential expression analysis between control and HS samples using R software. Four machine learning algorithms (SVM, RF, ANN, and lasso) and WCGNA were utilized to identify feature genes. GO, KEGG, Metascape, and GSVA were utilized for the enrichment analysis. CIBERSORT and ssGSEA were employed to analyze immune infiltration. Results A total of 29 DEGs were identified, with the majority showing up-regulation in HS. Enrichment analysis revealed their involvement in immune responses and cytokine activities. KEGG analysis highlighted pathways such as IL-17 signaling, rheumatoid arthritis, and TNF signaling in HS. Immune infiltration analysis revealed the predominant presence of neutrophils, monocytes, and CD8 T cells. Machine learning algorithms and WCGNA identified KYNU as a feature gene associated with HS. We have also identified 59 potential drugs for HS based on the DEGs. Additionally, ceRNA network analysis identified the MUC19_hsa-miR-382-5p_KYNU pathway as a potential regulatory pathway. Conclusions KYNU emerged as a feature gene associated with HS, and the ceRNA network analysis identified the MUC19_hsa-miR-382-5p_KYNU pathway as a potential regulator.
Prognostic significance of platelet-to-lymphocyte ratio (PLR) in patients with breast cancer treated with neoadjuvant chemotherapy: a meta-analysis

Objective Platelet-to-lymphocyte ratio (PLR), known as a key systemic inflammatory parameter, has been proved to be associated with response to neoadjuvant therapy in breast cancer (BC); however, the results remain controversial. This meta-analysis was carried out to evaluate the prognostic values of PLR in patients with BC treated with neoadjuvant chemotherapy (NACT). Design Meta-analysis. Data sources Relevant literature published on the following databases: PubMed, Embase, Web of Science databases and the Cochrane Library. Eligibility criteria All studies involving patients with BC treated with NACT and peripheral blood pretreatment PLR recorded were included. Data extraction and synthesis Two researchers independently extracted and evaluated HR/OR and its 95% CI of survival outcomes, pathological complete response (pCR) rate and clinicopathological parameters. Results The last search was updated to 31 December 2022. A total of 22 studies with 5533 patients with BC treated with NACT were enrolled in the final meta-analysis. Our results demonstrate that elevated PLR value appears to correlate with low pCR rate (HR 0.77, 95% CI 0.67 to 0.88, p<0.001, I2=75.80%, Ph<0.001) and poor prognosis, including overall survival (OS) (HR 1.90, 95% CI 1.39 to 2.59, p<0.001; I2=7.40%, Ph=0.365) and disease-free survival (HR 1.97, 95% CI 1.56 to 2.50, p<0.001; I2=0.0%, Ph=0.460). Furthermore, PLR level was associated with age (OR 0.86, 95% CI 0.79 to 0.93, p<0.001, I2=40.60%, Ph=0.096), menopausal status (OR 0.83, 95% CI 0.76 to 0.90, p<0.001, I2=50.80%, Ph=0.087) and T stage (OR 1.05, 95% CI 1.00 to 1.11, p=0.035; I2=70.30%, Ph=0.005) of patients with BC. Conclusions This meta-analysis demonstrated that high PLR was significantly related to the low pCR rate, poor OS and disease-free survival (DFS) of patients with BC treated with NACT. Therefore, PLR can be used as a potential predictor biomarker for the efficacy of NACT in BC.
PbMg 1/3 Nb 2/3 O3 dielectric aging in the freezing temperature region

Aging of the relaxors and PbMg 1/3 Nb 2/3 O3 in particular was extensively studied in last two decades. Most of the results were related to the low temperature glass-like region. No systematic data around the freezing temperatures were reported. To cover this still missing information we have studied the evolution of the dielectric spectra in the broad frequency region from 10−1 Hz to 106 Hz both below and above the freezing temperature Tf≈ 240 K. Below freezing temperature the existence of the earlier reported waiting time–frequency scaling at frequencies below ≈50 Hz is confirmed. At higher frequencies this deviation from the scaling is observed that can be tentatively attributed to the complexity of the relaxing entities. Above Tf aging is observed only in the restricted frequency interval below the maximum of the dielectric loss spectrum. The observed effect can be attributed to the hardening and narrowing of the dielectric loss spectra and decreasing of the dielectric strength with time. The explanation is proposed based on the concept of the creation of the degenerate polar nanoregions covering several chemically ordered regions (COR) (multi PNRs—MPNRs). These MPNRs are large compare to the PNRs located at the single CORs and some of them may become frozen resulting in the described spectra changes.
Gene Duplication, Shifting Selection, and Dosage Balance of Silicon Transporter Proteins in Marine and Freshwater Diatoms

Abstract Numerous factors shape the evolution of protein-coding genes, including shifts in the strength or type of selection following gene duplications or changes in the environment. Diatoms and other silicifying organisms use a family of silicon transporters (SITs) to import dissolved silicon from the environment. Freshwaters contain higher silicon levels than oceans, and marine diatoms have more efficient uptake kinetics and less silicon in their cell walls, making them better competitors for a scarce resource. We compiled SITs from 37 diatom genomes to characterize shifts in selection following gene duplications and marine–freshwater transitions. A deep gene duplication, which coincided with a whole-genome duplication, gave rise to two gene lineages. One of them (SIT1–2) is present in multiple copies in most species and is known to actively import silicon. These SITs have evolved under strong purifying selection that was relaxed in freshwater taxa. Episodic diversifying selection was detected but not associated with gene duplications or habitat shifts. In contrast, genes in the second SIT lineage (SIT3) were present in just half the species, the result of multiple losses. Despite conservation of SIT3 in some lineages for the past 90–100 million years, repeated losses, relaxed selection, and low expression highlighted the dispensability of SIT3, consistent with a model of deterioration and eventual loss due to relaxed selection on SIT3 expression. The extensive but relatively balanced history of duplications and losses, together with paralog-specific expression patterns, suggest diatoms continuously balance gene dosage and expression dynamics to optimize silicon transport across major environmental gradients.
Cognitive-motor dual-task training improves dynamic stability during straight and curved gait in patients with multiple sclerosis: a randomized controlled trial

BACKGROUND Multiple Sclerosis (MS) is a chronic inflammatory, demyelinating, degenerative disease of the central nervous system and the second most frequent cause of permanent disability in young adults. One of the most common issues concerns the ability to perform postural and gait tasks while simultaneously completing a cognitive task (namely, dual-task DT). AIM Assessing cognitive-motor dual-task training effectiveness in patients with Multiple Sclerosis (PwMS) for dynamic gait quality when walking on straight, curved, and blindfolded paths. DESIGN Two-arm single-blind randomized controlled trial. Follow-up at 8 weeks. SETTING Neurorehabilitation Hospital. POPULATION A sample of 42 PwMS aged 28-71, with a score of 4.00±1.52 on the Expanded Disability Status Scale were recruited. METHODS Participants were randomized in conventional (CTg) neurorehabilitation and dual-task training (DTg) groups and received 12 sessions, 3 days/week/4 weeks. They were assessed at baseline (T0), after the treatment (T1), and 8 weeks after the end of the treatment (T2) through Mini-BESTest, Tinetti Performance Oriented Mobility Assessment, Modified Barthel Index, and a set of spatiotemporal parameters and gait quality indices related to stability, symmetry, and smoothness of gait extracted from initial measurement units (IMUs) data during the execution of the 10-meter Walk Test (10mWT), the Figure-of-8 Walk Test (Fo8WT) and the Fukuda Stepping Test (FST). RESULTS Thirty-one PwMS completed the trial at T2. Significant improvement within subjects was found in Mini-BESTest scores for DTg from T0 to T1. The IMU-based assessment indicated significant differences in stability (P<0.01) and smoothness (P<0.05) measures between CTg and DTg during 10mWT and Fo8WT. Substantial improvements (P<0.017) were also found in the inter-session comparison, primarily for DTg, particularly for stability, symmetry, and smoothness measures. CONCLUSIONS This study supports the effectiveness of DT in promoting dynamic motor abilities in PwMS. CLINICAL REHABILITATION IMPACT Cognitive-motor DT implemented into the neurorehabilitation conventional program could be a useful strategy for gait and balance rehabilitation.
The Primary Prevention of Poststroke Epilepsy in Patients With Middle Cerebral Artery Infarct: Protocol for a Randomized Controlled Trial

Background Poststroke epilepsy poses a significant clinical challenge for individuals recovering from strokes, leading to a less favorable long-term outlook and increased mortality rates. Existing studies have primarily concentrated on administering antiseizure or anticonvulsant treatments only after the onset of late-onset seizures, without intervening during the epileptogenesis phase following a stroke. Objective This research protocol is designed to conduct a randomized controlled trial to assess whether the early, preventive introduction of low-dose antiepileptic drug therapy (levetiracetam [LEV] or perampanel [PER]) in patients who have experienced middle cerebral artery (MCA) infarction can reduce the risk of developing poststroke epilepsy (primary prevention). Methods Participants with MCA infarction, either with or without reperfusion treatments, will be recruited and promptly receive preventive intervention within 72 hours of the stroke occurrence. These participants will be randomly assigned to receive either PER (4 mg per day), LEV (1000 mg per day), or a placebo that matches the active drugs. This treatment will continue for 12 weeks after allocation. Brain magnetic resonance imaging will be used to confirm the presence of MCA territory infarction, and an electroencephalography will be used to ensure the absence of epileptiform discharges or electrographic seizures at the time of the stroke. All participants will undergo follow-up assessments for 72 weeks after allocation. Results The primary outcome under evaluation will be the incidence of poststroke epilepsy in the 3 groups following the 18-month study period. Secondary outcomes will encompass the time to the occurrence of the first seizure, the severity of seizures, any treatment-related adverse events, and the modified Rankin scale score at 3 and 18 months. Exploratory outcomes will involve comparing the effectiveness and safety of PER and LEV. Conclusions We anticipate that the intervention groups will experience a lower incidence and reduced severity of poststroke epilepsy compared to the control group after 18 months. We aim to establish evidence supporting the potential preventive effects of LEV and PER on poststroke seizures and epilepsy in patients with MCA infarction, as well as to explore the antiepileptogenic potential of both LEV and PER in patients with major ischemic strokes. Trial Registration ClinicalTrials.gov NCT04858841; https://clinicaltrials.gov/study/NCT04858841 International Registered Report Identifier (IRRID) DERR1-10.2196/49412
TRIASSIC CHRONOSTRATIGRAPHIC DATABASE AND A DISPLAY INTERFACE

The numerical ages on the Triassic time scale have undergone a major revision since 2002 and will probably remain in flux for some intervals for the next few years. At the same time, the inter-calibrations and taxonomic nomenclature among and within different faunal groups, magnetic polarity zones, sequences and other stratigraphic scales are constantly being revised. This can create headaches, not only for Triassic specialists, but for other geoscientists working with Triassic strata. Ideally, as new information becomes available and is confirmed, an online public database and visualization system would allow users to access both the current “standard” scales and annotations that explain the inter-calibrations, uncertainties and history of those scales. This ideal system will probably never be practical, but a greatly simplified version is possible. A project of the International Commission on Stratigraphy (ICS) is to provide detailed global and regional “reference” scales of Earth history. Such scales integrate biostratigraphy (zones, datums for marine and terrestrial realms), sea-level (curves, sequences), geochemistry (trends, events), magnetic polarity chrons and astronomical cycles. These summarize our current consensus on the inter-calibration of events, their
Emergence and persistent spread of carbapenemase-producing Klebsiella pneumoniae high-risk clones in Greek hospitals, 2013 to 2022

Background Preliminary unpublished results of the survey of carbapenem- and/or colistin-resistant Enterobacterales (CCRE survey) showed the expansion of carbapenemase-producing Klebsiella pneumoniae (CPKP) sequence type (ST) 39 in 12 of 15 participating Greek hospitals in 2019. Aim We conducted a rapid survey to determine the extent of spread of CPKP high-risk clones in Greek hospitals in 2022 and compare the distribution of circulating CPKP clones in these hospitals since 2013. Methods We analysed whole genome sequences and epidemiological data of 310 K. pneumoniae isolates that were carbapenem-resistant or ‘susceptible, increased exposure’ from Greek hospitals that participated in the European survey of carbapenemase-producing Enterobacteriaceae (EuSCAPE, 2013–2014), in the CCRE survey (2019) and in a national follow-up survey (2022) including, for the latter, an estimation of transmission events. Results Five K. pneumoniae STs including ST258/512 (n = 101 isolates), ST11 (n = 93), ST39 (n = 56), ST147 (n = 21) and ST323 (n = 13) accounted for more than 90% of CPKP isolates in the dataset. While ST11, ST147 and ST258/512 have been detected in participating hospitals since 2013 and 2014, KPC-2-producing ST39 and ST323 emerged in 2019 and 2022, respectively. Based on the defined genetic relatedness cut-off, 44 within-hospital transmission events were identified in the 2022 survey dataset, with 12 of 15 participating hospitals having at least one within-hospital transmission event. Conclusion The recent emergence and rapid spread of new high-risk K. pneumoniae clones in the Greek healthcare system related to within-hospital transmission is of concern and highlights the need for molecular surveillance and enhanced infection prevention and control measures.
Staff perceptions towards virtual reality-motivated treadmill exercise for care home residents: a qualitative feedback study with key stakeholders and follow-up interview with technology developer

Objectives Health and care resources are under increasing pressure, partly due to the ageing population. Physical activity supports healthy ageing, but motivating exercise is challenging. We aimed to explore staff perceptions towards a virtual reality (VR) omnidirectional treadmill (MOTUS), aimed at increasing physical activity for older adult care home residents. Design Interactive workshops and qualitative evaluation. Settings Eight interactive workshops were held at six care homes and two university sites across Cornwall, England, from September to November 2021. Participants Forty-four staff participated, including care home, supported living, clinical care and compliance managers, carers, activity coordinators, occupational therapists and physiotherapists. Interventions Participants tried the VR treadmill system, followed by focus groups exploring device design, potential usefulness or barriers for care home residents. Focus groups were audio-recorded, transcribed verbatim and thematically analysed. We subsequently conducted a follow-up interview with the technology developer (September 2022) to explore the feedback impact. Results The analysis produced seven key themes: anticipated benefits, acceptability, concerns of use, concerns of negative effects, suitability/unsuitability, improvements and current design. Participants were generally positive towards VR to motivate care home residents’ physical activity and noted several potential benefits (increased exercise, stimulation, social interaction and rehabilitation). Despite the reported potential, staff had safety concerns for frail older residents due to their standing position. Participants suggested design improvements to enhance safety, usability and accessibility. Feedback to the designers resulted in the development of a new seated VR treadmill to address concerns about falls while maintaining motivation to exercise. The follow-up developer interview identified significant value in academia–industry collaboration. Conclusion The use of VR-motivated exercise holds the potential to increase exercise, encourage reminiscence and promote meaningful activity for care home residents. Staff concerns resulted in a redesigned seated treadmill for those too frail to use the standing version. This novel study demonstrates the importance of stakeholder feedback in product design.