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Identifying the driver nodes of a network has crucial implications in biological systems from unveiling causal interactions to informing effective intervention strategies. Despite recent advances in network control theory, results remain inaccurate as the number of drivers becomes too small compared to the network size, thus limiting the concrete usability in many real-life applications. To overcome this issue, we introduced a framework that integrates principles from spectral graph theory and output controllability to project the network state into a smaller topological space formed by the Laplacian network structure. Through extensive simulations on synthetic and real networks, we showed that a relatively low number of projected components can significantly improve the control accuracy. By introducing a new low-dimensional controllability metric we experimentally validated our method on N = 6134 human connectomes obtained from the UK-biobank cohort. Results revealed previously unappreciated influential brain regions, enabled to draw directed maps between differently specialized cerebral systems, and yielded new insights into hemispheric lateralization. Taken together, our results offered a theoretically grounded solution to deal with network controllability and provided insights into the causal interactions of the human brain., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2025 Ben Messaoud 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.)

Background/Introduction: Cardiac implantable electronic devices and their integrated thoracic impedance sensors have been used to detect sleep apnea for over a decade now. Despite their usage in daily clinical practice, there are only limited data on their diagnostic accuracy. Methods: AIRLESS and UPGRADE were prospective investigator-driven trials meant to validate the AP scan ® (Boston Scientific, Marlborough, MA, USA) in heart failure cohorts. Patients, who either fulfilled the criteria for implantation of an implantable cardioverter-defibrillator (ICD), cardiac resynchronization therapy (CRT), or upgrading to CRT according to most recent guidelines at the time of study conduction, were eligible for enrolment. Sleep apnea and its severity, measured by apnea-hypopnea index (AHI), were assessed by polysomnography. For direct comparison, the apnea sensor-derived AP scan ® was used from the identical night. Results: Overall, 80 patients were analyzed. Median AHI was 21.6 events/h (7.1-34.7), while median AP scan ® was 33.0 events/h (26.0-43.0). In the overall cohort, the sensor-derived AP scan ® correlated significantly with the AHI (r = 0.61, p < 0.001) with a mean difference (MD) of -12.6 (95% confidence interval (CI) -38.2 to 13.0). Furthermore, the AP scan ® was found to correlate well with the AHI in patients with obstructive sleep apnea r = 0.73, p = 0.011, MD -5.2, 95% CI -22.7 to 12.3), but not central sleep apnea (r = 0.28, p = 0.348, MD -10.4, 95% CI -35.4 to 14.6). Conclusions: In an exclusive heart failure cohort, the AP scan ® correlated well with the PSG-derived AHI. A similar correlation was found in most subgroups except for patients suffering from central sleep apnea.

Background: Obstructive sleep apnoea (OSA) is a common chronic respiratory disease associated with a high burden of disabilities related to sleepiness and reduced quality of life. Despite first-line treatment with continuous positive airway pressure (CPAP) therapy, many patients experience residual excessive daytime sleepiness (EDS). The aim of this study is to compare the relative efficacy and safety of medications authorised for this indication in Europe and/or the United States (modafinil/armodafinil, solriamfetol, and pitolisant) for OSA., Methods: In this systematic review and network meta-analysis, randomised controlled trials (RCTs) that compared the efficacy and safety of authorised medications for adult patients with OSA were identified by literature searches of PubMed, Embase and ClinicalTrials.gov databases (up to 12 June 2024). The primary efficacy endpoint was combined Epworth Sleepiness Scale (ESS) and Oxford Sleep Resistance (OSLER)/Maintenance of Wakefulness Test (MWT) Z-scores. Quality of life (QoL), overall and specific cardiovascular safety, and benefit-risk ratios were calculated. The study was registered with PROSPERO: CRD42023434640., Findings: Of 4017 studies identified, a total of 20 RCTs involving 4015 patients were included. Analysis of combined subjective (ESS) and objective (OSLER/MWT) efficacy outcome Z-scores showed that solriamfetol (150 mg; effect size [ES] = 0.66 [95% CI: 0.36, 0.96]), pitolisant (20 mg; ES = 0.66 [95% CI: 0.44, 0.88]), and modafinil (200 mg; ES = 0.54: [95% CI: 0.33, 0.74]); 400 mg; ES = 0.54 [95% CI: 0.42, 0.65]) had a clinically meaningful improvement in efficacy. P-scores ranked placebo, then pitolisant, modafinil 200 mg, modafinil 400 mg and solriamfetol for overall safety; and pitolisant, then solriamfetol, modafinil 400 mg and modafinil 200 mg for benefit-risk ratio., Interpretation: Pitolisant, solriamfetol and modafinil had comparable efficacy for maintaining wakefulness in patients with OSA. Pitolisant had a better safety profile and benefit-risk ratio compared with solriamfetol and modafinil. The overall and cardiovascular safety risk ratios suggest that pitolisant might be the best candidate for patients with OSA with multiple cardiovascular comorbidities., Funding: Bioprojet., Competing Interests: This analysis has been sponsored by Bioprojet Pharma. Jean-Louis Pépin has received grants or contracts from the National Research Agency, and lecture fees and travel grants from RESMED, SEFAM and Bioprojet. Jerryll Asin received support from Bioprojet for attending meetings and/or travel; received grants or contracts (paid to his institute) from Philips, Somnomed and Zoll Respicardia; consulting fees (paid to his institute) from Zoll Respicardia; participation on a Data Safety Monitoring Board or Advisory Board (paid to his institute) from Zoll Respicardia; member of the Dutch Association of Sleep Medicine (no payment). Ferran Barbé received support from Bioprojet for attending meetings and/or travel; received grants or contracts for sleep research from Instituto de Salud Carlos III. Maria Bonsignore received payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Bioprojet and Takeda; support for attending meetings and/or travel from Bioprojet; participation on a Data Safety Monitoring Board or Advisory Board for Bioprojet. Winfried Randerath received study funding from Bioprojet; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Heinen & Löwenstein, Habel Medizintechnik, Jazz Pharmaceuticals, Inspire, Philips Respironics and Bioprojet; support for attending meetings and/or travel from Heinen & Löwenstein, Habel Medizintechnik, Jazz Pharmaceuticals, Philips Respironics and Bioprojet; personal fees for participation on a Data Safety Monitoring Board or Advisory Board for Bioprojet, Jazz Pharmaceuticals and Procter & Gamble; unpaid roles with the European Respiratory Society Head Assembly 4, Sleep Disordered Breathing (until September 2023), Guidelines Director elect 2024 and the German Respiratory Society, Secretary General (until March 2024), authorised member since March 2024. Johan Verbraecken received study funding from Bioprojet; support for teaching courses (paid to his institute) from Air Liquide, Bioprojet, Inspire Medical Systems, Löwenstein Medical, Medidis, Mediq Tefa, Micromed OSG, Philips, ProSomnus, ResMed, Sefam, SomnoMed, SOS Oxygène, Tilman, Total Care, Vivisol, and Zoll Itamar outside the submitted work; royalties or licenses (paid to his institute) from Epilog; consulting fees (paid to his institute) from Desitin and Epilog; payment of honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events (paid to his institute) from Atos Medical, Idorsia, Inspire Medical Systems; support for attending meetings and/or travel from Bioprojet; past-President (since 2020) of the Belgian Association for Sleep Research and Sleep Medicine. Yves Dauvilliers received payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educationa events from Jass Pharmaceuticals, Bioprojet, Takeda, UCB, Orexia, Idorsia and Avadel; support for attending meetings and/or travel from Jazz Pharmaceuticals, Bioprojet and Avadel; participation on a Data Safety Monitoring Board or Advisory Board for Idorsia. Raoua Ben Messaoud, Marie Joyeux-Faure and Sonya Craig have no declaration of interest., (© 2024 The Authors.)

In the central nervous system, the formation of myelin by oligodendrocytes (OLs) relies on the switch from the polymerization of the actin cytoskeleton to its depolymerization. The molecular mechanisms that trigger this switch have yet to be elucidated. Here, we identified P21-activated kinase 1 (PAK1) as a major regulator of actin depolymerization in OLs. Our results demonstrate that PAK1 accumulates in OLs in a kinase-inhibited form, triggering actin disassembly and, consequently, myelin membrane expansion. Remarkably, proteomic analysis of PAK1 binding partners enabled the identification of NF2/Merlin as its endogenous inhibitor. Our findings indicate that Nf2 knockdown in OLs results in PAK1 activation, actin polymerization, and a reduction in OL myelin membrane expansion. This effect is rescued by treatment with a PAK1 inhibitor. We also provide evidence that the specific Pak1 loss-of-function in oligodendroglia stimulates the thickening of myelin sheaths in vivo. Overall, our data indicate that the antagonistic actions of PAK1 and NF2/Merlin on the actin cytoskeleton of the OLs are critical for proper myelin formation. These findings have broad mechanistic and therapeutic implications in demyelinating diseases and neurodevelopmental disorders., (© 2024 The Author(s). GLIA published by Wiley Periodicals LLC.)

In a prospective cohort of OSA patients without comorbidities at inclusion, age, mean blood pressure, mean oxygen saturation and minimum oxygen saturation were associated with long-term incidence of severe health events https://bit.ly/3VyYEzC., Competing Interests: Conflict of interest: R. Tamisier reports grants or contracts from Bioprojet, outside the submitted work; consulting fees from Jazz, Bioprojet, Resmed and Isdorsia, outside the submitted work; payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing or educational events for Jazz, Bioprojet, Resmed, Inspire, Elivie and Isdorsia, outside the submitted work; support for attending meetings and/or travel from Agiradom and Elivie, outside the submitted work; and participation on a data safety monitoring or advisory board for Bioprojet and Narval (Resmed), outside the submitted work. Conflict of interest: J.L. Pépin reports support for the present manuscript from Air Liquide Foundation, Agiradom, AstraZeneca, Fisher and Paykel, Mutualia, Philips, Resmed, and Vitalaire; and consulting fees from Agiradom, AstraZeneca, Boehringer Ingelheim, Jazz Pharmaceutical, Night Balance, Philips, Resmed and Sefam, outside the submitted work. Conflict of interest: The remaining authors have nothing to disclose., (Copyright ©The authors 2024.)

Obstructive sleep apnea (OSA) induces intermittent hypoxia (IH), an independent risk factor for non-alcoholic fatty liver disease (NAFLD). While the molecular links between IH and NAFLD progression are unclear, immune cell-driven inflammation plays a crucial role in NAFLD pathogenesis. Using lean mice exposed to long-term IH and a cohort of lean OSA patients (n = 71), we conducted comprehensive hepatic transcriptomics, lipidomics, and targeted serum proteomics. Significantly, we demonstrated that long-term IH alone can induce NASH molecular signatures found in human steatohepatitis transcriptomic data. Biomarkers (PPARs, NRFs, arachidonic acid, IL16, IL20, IFNB, TNF-α) associated with early hepatic and systemic inflammation were identified. This molecular link between IH, sleep apnea, and steatohepatitis merits further exploration in clinical trials, advocating for integrating sleep apnea diagnosis in liver disease phenotyping. Our unique signatures offer potential diagnostic and treatment response markers, highlighting therapeutic targets in the comorbidity of NAFLD and OSA., Competing Interests: The authors declare no competing interests., (© 2024.)

Sleep apnea is nowadays recognized as a treatable chronic disease and awareness of it has increased, leading to an upsurge in demand for diagnostic testing. Conventionally, diagnosis depends on overnight polysomnography in a sleep clinic, which is highly human-resource intensive and ignores the night-to-night variability in classical sleep apnea markers, such as the apnea-hypopnea index. In this review, the authors summarize the main improvements that could be made in the sleep apnea diagnosis strategy; how technological innovations and multi-night home testing could be used to simplify, increase access, and reduce costs of diagnostic testing while avoiding misclassification of severity., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Obstructive sleep apnea (OSA) remains massively underdiagnosed, due to limited access to polysomnography (PSG), the highly complex gold standard for diagnosis. Performance scores in predicting OSA are evaluated for machine learning (ML) analysis applied to 3D maxillofacial shapes., Methods: The 3D maxillofacial shapes were scanned on 280 Caucasian men with suspected OSA. All participants underwent single night in-home or in-laboratory sleep testing with PSG (Nox A1, Resmed, Australia), with concomitant 3D scanning (Sense v2, 3D systems corporation, USA). Anthropometric data, comorbidities, medication, BERLIN, and NoSAS questionnaires were also collected at baseline. The PSG recordings were manually scored at the reference sleep center. The 3D craniofacial scans were processed by geometric morphometrics, and 13 different supervised algorithms, varying from simple to more advanced, were trained and tested. Results for OSAS recognition by ML models were then compared with scores for specificity and sensitivity obtained using BERLIN and NoSAS questionnaires., Results: All valid scans (n = 267) were included in the analysis (patient mean age: 59 ± 9 years; BMI: 27 ± 4 kg/m 2 ). For PSG-derived AHI≥15 events/h, the 56% specificity obtained for ML analysis of 3D craniofacial shapes was higher than for the questionnaires (Berlin: 50%; NoSAS: 40%). A sensitivity of 80% was obtained using ML analysis, compared to nearly 90% for NoSAS and 61% for the BERLIN questionnaire. The auROC score was further improved when 3D geometric morphometrics were combined with patient anthropometrics (auROC = 0.75)., Conclusion: The combination of 3D geometric morphometrics with ML is proposed as a rapid, efficient, and inexpensive screening tool for OSA., Trial Registration Number: NCT03632382; Date of registration: 15-08-2018., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: The capacity to diagnose obstructive sleep apnoea (OSA) must be expanded to meet an estimated disease burden of nearly one billion people worldwide. Validated alternatives to the gold standard polysomnography (PSG) will improve access to testing and treatment. This study aimed to evaluate the diagnosis of OSA, using measurements of mandibular movement (MM) combined with automated machine learning analysis, compared to in-home PSG., Methods: 40 suspected OSA patients underwent single overnight in-home sleep testing with PSG (Nox A1, ResMed, Australia) and simultaneous MM monitoring (Sunrise, Sunrise SA, Belgium). PSG recordings were manually analysed by two expert sleep centres (Grenoble and London); MM analysis was automated. The Obstructive Respiratory Disturbance Index calculated from the MM monitoring (MM-ORDI) was compared to the PSG (PSG-ORDI) using intraclass correlation coefficient and Bland-Altman analysis. Receiver operating characteristic curves (ROC) were constructed to optimise the diagnostic performance of the MM monitor at different PSG-ORDI thresholds (5, 15, and 30 events/hour)., Results: 31 patients were included in the analysis (58% men; mean (SD) age: 48 (15) years; BMI: 30.4 (7.6) kg/m 2 ). Good agreement was observed between MM-ORDI and PSG-ORDI (median bias 0.00; 95% CI -23.25 to + 9.73 events/hour). However, for 15 patients with no or mild OSA, MM monitoring overestimated disease severity (PSG-ORDI < 5: MM-ORDI mean overestimation + 5.58 (95% CI + 2.03 to + 7.46) events/hour; PSG-ORDI > 5-15: MM-ORDI overestimation + 3.70 (95% CI -0.53 to + 18.32) events/hour). In 16 patients with moderate-severe OSA ( n = 9 with PSG-ORDI 15-30 events/h and n = 7 with a PSG-ORD > 30 events/h), there was an underestimation (PSG-ORDI > 15: MM-ORDI underestimation -8.70 (95% CI -28.46 to + 4.01) events/hour). ROC optimal cut-off values for PSG-ORDI thresholds of 5, 15, 30 events/hour were: 9.53, 12.65 and 24.81 events/hour, respectively. These cut-off values yielded a sensitivity of 88, 100 and 79%, and a specificity of 100, 75, 96%. The positive predictive values were: 100, 80, 95% and the negative predictive values 89, 100, 82%, respectively., Conclusion: The diagnosis of OSA, using MM with machine learning analysis, is comparable to manually scored in-home PSG. Therefore, this novel monitor could be a convenient diagnostic tool that can easily be used in the patients' own home., Clinical Trial Registration: https://clinicaltrials.gov, identifier NCT04262557., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Kelly, Ben Messaoud, Joyeux-Faure, Terrail, Tamisier, Martinot, Le-Dong, Morrell and Pépin.)

Background: A particularly high burden of sleep apnoea is reported in patients treated with cardiac implants such as pacemakers and defibrillators. Sleep apnoea diagnosis remains a complex procedure mainly based on sleep and respiratory indices captured by polysomnography (PSG) or respiratory polygraphy (PG)., Aim: We aimed to evaluate the performance of implantable cardiac devices for sleep apnoea diagnosis compared to reference methods., Method: Systematic structured literature searches were performed in PubMed, Embase and. Cochrane Library was performed to identify relevant studies. Quantitative characteristics of the studies were summarized and a qualitative synthesis was performed by a randomized bivariate meta-analysis and completed by pre-specified sensitivity analyses for different implant types and brands., Results: 16 studies involving 999 patients met inclusion criteria and were included in the meta-analysis. The majority of patients were men, of mean age of 64 ± 4.6 years. Sensitivity of cardiac implants for sleep apnoea diagnosis ranged from 60 to 100%, specificity from 50 to 100% with a prevalence of sleep apnoea varying from 22 to 91%. For an apnoea-hypopnoea index threshold ≥30 events/h during polysomnography (corresponding to severe sleep apnoea), the overall performance of the implants was relevant with a sensitivity of 78% and a specificity of 79%. Subgroup analyses on implant type and brand provided no additional information owing to the small number of studies., Conclusion: The respiratory disturbance index provided by cardiac implants is clinically relevant and might improve access to sleep apnoea diagnosis in at-risk cardiovascular populations. PROSPERO Registration number: CRD42020181656., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Study Objectives: The COVID-19 pandemic has had dramatic effects on society and people's daily habits. In this observational study, we recorded objective data on sleep macro- and microarchitecture repeatedly over several nights before and during the COVID-19 government-imposed lockdown. The main objective was to evaluate changes in patterns of sleep duration and architecture during home confinement using the pre-confinement period as a control., Methods: Participants were regular users of a sleep-monitoring headband that records, stores, and automatically analyzes physiological data in real time, equivalent to polysomnography. We measured sleep onset duration, total sleep time, duration of sleep stages (N2, N3, and rapid eye movement [REM]), and sleep continuity. Via the user's smartphone application, participants filled in questionnaires on how lockdown changed working hours, eating behavior, and daily life at home. They also filled in the Insomnia Severity Index, reduced Morningness-Eveningness Questionnaire, and Hospital Anxiety and Depression Scale questionnaires, allowing us to create selected subgroups., Results: The 599 participants were mainly men (71%) of median age 47 (interquartile range: 36-59). Compared to before lockdown, during lockdown individuals slept more overall (mean +3·83 min; SD: ±1.3), had less deep sleep (N3), more light sleep (N2), and longer REM sleep (mean +3·74 min; SD: ±0.8). They exhibited less weekend-specific changes, suggesting less sleep restriction during the week. Changes were most pronounced in individuals reporting eveningness preferences, suggesting relative sleep deprivation in this population and exacerbated sensitivity to societal changes., Conclusion: This unique dataset should help us understand the effects of lockdown on sleep architecture and on our health., (© Sleep Research Society 2021. Published by Oxford University Press on behalf of the Sleep Research Society.)

New construction for nonlinear reduced unknown input observer UIO design is purposed. The main concept consists of using the estimate of error also the parameters used in mean value theorem (MVT) for the observer's design. This observer is founded principally on MVT and the genetic algorithm (GA). A Lyapunov function is utilised for ensuring the stability also the observer's gain is automatically resolved. Lastly, three practical realisations address to the secure communication problem., 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 © 2020 ISA. Published by Elsevier Ltd. All rights reserved.)

The tumor microenvironment (TME) is composed of dynamic and complex networks composed of matrix substrates, extracellular matrix (ECM), non-malignant cells, and tumor cells. The TME is in constant evolution during the disease progression, most notably through gradual stiffening of the stroma. Within the tumor, increased ECM stiffness drives tumor growth and metastatic events. However, classic in vitro strategies to study the TME in cancer lack the complexity to fully replicate the TME. The quest to understand how the mechanical, geometrical, and biochemical environment of cells impacts their behavior and fate has been a major force driving the recent development of new technologies in cell biology research. Despite rapid advances in this field, many challenges remain in order to bridge the gap between the classical culture dish and the biological reality of actual tissue. Microfabrication coupled with microfluidic approaches aim to engineer the actual complexity of the TME. Moreover, TME bioengineering allows artificial modulations with single or multiple cues to study different phenomena occurring in vivo. Some innovative cutting-edge tools and new microfluidic approaches could have an important impact on the fields of biology and medicine by bringing deeper understanding of the TME, cell behavior, and drug effects.

The impact of chronic cadmium exposure and slow accumulation on the occurrence and development of diabetes is controversial for human populations. Islets of Langerhans play a prominent role in the etiology of the disease, including by their ability to secrete insulin. Conversion of glucose increase into insulin secretion involves mitochondria. A rat model of pancreatic β-cells was exposed to largely sub-lethal levels of cadmium cations applied for the longest possible time. Cadmium entered cells at concentrations far below those inducing cell death and accumulated by factors reaching several hundred folds the basal level. The mitochondria reorganized in response to the challenge by favoring fission as measured by increased circularity at cadmium levels already ten-fold below the median lethal dose. However, the energy charge and respiratory flux devoted to adenosine triphosphate synthesis were only affected at the onset of cellular death. The present data indicate that mitochondria participate in the adaptation of β-cells to even a moderate cadmium burden without losing functionality, but their impairment in the long run may contribute to cellular dysfunction, when viability and β-cells mass are affected as observed in diabetes., Competing Interests: The authors declare no conflict of interest. The founding sponsors had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, and in the decision to publish the results.