Clinical applications of artificial intelligence in sleep medicine: a sleep clinician’s perspective

Sleep And Breathing, Journal Year: 2022, Volume and Issue: 27(1), P. 39 - 55

Published: March 9, 2022

Language: Английский

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Circadian Regulation of Drug Responses: Toward Sex-Specific and Personalized Chronotherapy

The Annual Review of Pharmacology and Toxicology, Journal Year: 2023, Volume and Issue: 64(1), P. 89 - 114

Published: Sept. 19, 2023

Today's challenge for precision medicine involves the integration of impact molecular clocks on drug pharmacokinetics, toxicity, and efficacy toward personalized chronotherapy. Meaningful improvements tolerability and/or medications through proper administration timing have been confirmed over past decade immunotherapy chemotherapy against cancer, as well commonly used pharmacological agents in cardiovascular, metabolic, inflammatory, neurological conditions. Experimental human studies recently revealed sexually dimorphic circadian responses. Dedicated randomized clinical trials should now aim to issue recommendations daily medical practice, integrating innovative technologies remote longitudinal monitoring metrics, statistical prediction clock function from single-timepoint biopsies, multiscale biorhythmic mathematical modelling. Importantly, chronofit patients with a robust function, who would benefit most chronotherapy, need be identified. Conversely, nonchronofit could emerging class chronobiotics targeting clock.

Language: Английский

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Circadian rhythm disruption in critically ill patients

Acta Physiologica, Journal Year: 2023, Volume and Issue: 238(1)

Published: March 14, 2023

Abstract Patients admitted to the intensive care unit (ICU) are in need of continuous organ replacement strategies and specialized care, for example because neurological dysfunction, cardio‐pulmonary instability, liver or kidney failure, trauma, hemorrhagic septic shock even preterm birth. The 24‐h nursing interventions provided critically ill patients significantly limit resting and/or recovery phases. Consecutively, patient's endogenous circadian rhythms misaligned disrupted, which turn may interfere with their critical condition. A more thorough understanding complex interactions effectors tissue‐specific molecular clocks could therefore serve as potential means enhancing personalized treatment patients, conceivably restoring network thus accelerating physical neurocognitive recovery. This review addresses overarching issue how affected disturbed newborns adults ICU, whether conflicting external environmental cues ICU environment further promote disruption severity illness. We direct special attention influence cell‐type specific on dysfunctions such brain pneumonia‐ ventilator‐associated lung inflammation, cardiovascular shock. Finally, we address rhythm stabilization enhance accelerate clinical

Language: Английский

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TimeTeller for timing health: The potential of circadian medicine to improve performance, prevent disease and optimize treatment

Frontiers in Digital Health, Journal Year: 2023, Volume and Issue: 5

Published: April 18, 2023

Circadian medicine, the study of effects time on health and disease has seen an uprising in recent years as a means to enhance performance, optimize treatment timing. Our endogenous generating system -the circadian clock- regulates behavioural, physiological cellular processes. Disruptions clock, via external factors like shift work or jet lag, internal perturbations such genetic alterations, are linked increased risk various diseases obesity, diabetes, cardiovascular cancer. By aligning individual's clock with optimal times for performing daily routines, physical mental also effectiveness certain therapies can be improved. Despite benefits lack non-invasive tools characterizing limits potential field. TimeTeller is molecular/digital tool characterization rhythms prediction including timing, unlock medicine implementing it settings. Given multiple known potentially yet unknown dependent individual rhythms, utility this emerging biomarker best exploited data driven, personalized use cases, using information across lifestyle, care, research

Language: Английский

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Skeletal muscle gene expression dysregulation in long-term spaceflights and aging is clock-dependent

npj Microgravity, Journal Year: 2023, Volume and Issue: 9(1)

Published: April 3, 2023

The circadian clock regulates cellular and molecular processes in mammals across all tissues including skeletal muscle, one of the largest organs human body. Dysregulated rhythms are characteristic aging crewed spaceflight, associated with, for example, musculoskeletal atrophy. Molecular insights into spaceflight-related alterations regulation muscle still missing. Here, we investigated potential functional consequences disruptions on using published omics datasets obtained from spaceflights other clock-altering, external (fasting exercise), or internal (aging) conditions Earth. Our analysis identified network muscle-associated pathways, as a result spaceflight duration mice, which resembles aging-related gene expression changes observed humans Earth (e.g., ATF4 downregulation, with atrophy). Furthermore, according to our results, factors such exercise fasting lead core-clock network, may compensate disruption during spaceflights. Thus, maintaining functioning is crucial ameliorate unphysiological atrophy reported among astronauts.

Language: Английский

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A mathematical model of the circadian clock and drug pharmacology to optimize irinotecan administration timing in colorectal cancer

Computational and Structural Biotechnology Journal, Journal Year: 2021, Volume and Issue: 19, P. 5170 - 5183

Published: Jan. 1, 2021

Scheduling anticancer drug administration over 24 h may critically impact treatment success in a patient-specific manner. Here, we address personalization of timing using novel mathematical model irinotecan cellular pharmacokinetics and –dynamics linked to representation the core clock predict toxicity colorectal cancer (CRC) model. The is fitted three different scenarios: mouse liver, where metabolism mainly occurs, two human cell lines representing an vitro experimental system for progression. Our successfully recapitulates quantitative circadian datasets mRNA protein expression together with timing-dependent cytotoxicity data. also discriminates time-dependent between cells, suggesting that can be optimized according their clock. results show degradation mediating activation, as well oscillation death rate play important role variations toxicity. In future, this used support personalized scheduling by predicting optimal based on patient's gene profile.

Language: Английский

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It’s About Time: The Circadian Network as Time-Keeper for Cognitive Functioning, Locomotor Activity and Mental Health

Frontiers in Physiology, Journal Year: 2022, Volume and Issue: 13

Published: April 25, 2022

A variety of organisms including mammals have evolved a 24h, self-sustained timekeeping machinery known as the circadian clock (biological clock), which enables to anticipate, respond, and adapt environmental influences such daily light dark cycles. Proper functioning plays pivotal role in temporal regulation wide range cellular, physiological, behavioural processes. The disruption rhythms was found be associated with onset progression several pathologies sleep mental disorders, cancer, neurodegeneration. Thus, health disease, its clinical applications, gained increasing attention, but exact mechanisms underlying require further work integration evidence from different research fields. In this review, we address current knowledge regarding molecular circuits generators essential synchrony healthy organism. particular, discuss context behaviour cognitive functioning, delineating how loss tight interplay is linked pathological development focus on disorders We describe emerging new aspects link between physical exercise-induced usage activator positive impact delaying certain neurodegeneration brain-related disorders. Finally, recent epidemiological pointing an important health.

Language: Английский

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Small-molecule modulators of the circadian clock: Pharmacological potentials in circadian-related diseases

Drug Discovery Today, Journal Year: 2021, Volume and Issue: 26(7), P. 1620 - 1641

Published: March 27, 2021

Language: Английский

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Long-term continuous positive airway pressure treatment ameliorates biological clock disruptions in obstructive sleep apnea

EBioMedicine, Journal Year: 2021, Volume and Issue: 65, P. 103248 - 103248

Published: Feb. 26, 2021

BackgroundObstructive Sleep Apnea (OSA) is a highly prevalent and underdiagnosed sleep disorder. Recent studies suggest that OSA might disrupt the biological clock, potentially causing or worsening OSA-associated comorbidities. However, effect of treatment on clock disruption not fully understood.MethodsThe impact short- (four months) long-term (two years) treatment, with Continuous Positive Airway Pressure (CPAP), was investigated at four time points within 24 h, in patients relative to controls subjects (no OSA) same sex age group, case-control study. Plasma melatonin cortisol, body temperature expression levels rhythmicity eleven genes peripheral blood mononuclear cells (PBMCs) were assessed. Additional computational tools used for detailed data analysis.FindingsOSA impacts outputs several PBMCs. Neither nor reverted OSA-induced alterations genes. able re-establish plasma cortisol temperature. Machine learning methods could discriminate from untreated patients. Following distinction between disappeared, suggesting closer similarity phenotypes.InterpretationOSA alters clock-related characteristics differentially respond CPAP treatment. Long-term more efficient counteracting but obtained results it effective. A better understanding may open new avenues diagnosis, monitoring

Language: Английский

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Modeling the Circadian Control of the Cell Cycle and Its Consequences for Cancer Chronotherapy

Biology, Journal Year: 2023, Volume and Issue: 12(4), P. 612 - 612

Published: April 18, 2023

The mammalian cell cycle is governed by a network of cyclin/Cdk complexes which signal the progression into successive phases division cycle. Once coupled to circadian clock, this produces oscillations with 24 h period such that each phase synchronized day-night Here, we use computational model for clock control investigate entrainment in population cells characterized some variability kinetic parameters. Our numerical simulations showed successful and synchronization are only possible sufficient amplitude an autonomous close h. Cellular heterogeneity, however, introduces cells. Many cancer have disrupted or compromised control. In these conditions, runs independently leading lack When coupling weak, largely impacted, but maintain tendency divide at specific times day. These differential features between healthy can be exploited optimize timing anti-cancer drug administration order minimize their toxicity maximize efficacy. We then used our simulate chronotherapeutic treatments predict optimal drugs targeting Although qualitative, highlights need better characterize cellular heterogeneity populations as well consequences design chronopharmacological protocols.

Language: Английский

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