BackgroundSleep-wake-circadian disorders are prevalent and contribute substantially to morbidity, mortality and reduced quality of life. Evaluation in real-world settings is essential to capture their complexity and association with long-term outcomes. Most sleep-wake registries are restricted to selected populations, lack systematic integration of objective sleep-wake-circadian assessments with the clinical data and provide limited follow-up. To address these limitations, we established the Bern Sleep-Wake Registry based on real-world data from a tertiary University Hospital sleep center.

MethodsThe registry includes data from patients referred to the multidisciplinary Sleep-Center at Inselspital, University Hospital Bern (founded in 1990), from the year 2000 onwards who underwent at least one objective assessment such as polysomnography, daytime sleep-wake recordings, vigilance tests, and actigraphy. The registry integrates clinical information, questionnaire scores, outputs of objective assessments and raw signal data, and is regularly updated to incorporate new patients and longitudinal follow-up information.

ResultsAs of September 2025, records from over 11000 patients were evaluated (median age: 50 years (interquartile range 36, 61); 65% male). The most common sleep-wake-circadian disorders were "sleep-related breathing disorders" (67%), "insomnia disorders" (15%) and "central disorders of hypersomnolence" (9%). Available assessments included more than 12000 polysomnographies, 2400 multiple sleep latency tests, 2100 maintenance of wakefulness tests, 1800 vigilance tests and 4500 actigraphies.

ConclusionsBy longitudinally integrating multimodal deep clinical phenotyping with objective assessments and raw physiological signals, the Bern Sleep-Wake Registry provides a foundation for investigating disease trajectories, identifying novel biomarkers and developing data-driven approaches to precise diagnosis, prognosis and individualized treatment.

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IsomiR Utility in ALS Prognostication

- Posted by system in English

Significance of the Topic:

Amyotrophic Lateral Sclerosis (ALS) is a devastating neurodegenerative disease with limited treatment options. Early diagnosis and prognostication are critical in managing ALS, as they can significantly impact the quality of life for patients and their caregivers. The discovery of reliable biomarkers for ALS can provide valuable insights into disease progression and enable clinicians to develop more effective treatment strategies.

Importance:

The identification of plasma isomiRs as potential biomarkers for ALS is significant because it opens up new avenues for non-invasive monitoring of disease progression and response to treatment. IsomiRs are microRNA isoforms that are distinct from their parent microRNAs, and their presence in the plasma can be indicative of cellular stress or damage. The potential utility of isomiRs as biomarkers for neurodegenerative diseases is an area of active research, and this study contributes to our understanding of their role in ALS.

Timeliness:

The study's focus on plasma isomiRs as biomarkers for ALS is timely, given the growing interest in using liquid biopsies for disease diagnosis and monitoring. Liquid biopsies offer a non-invasive and cost-effective way to monitor disease progression and response to treatment, making them an attractive option for clinicians and researchers.

Relevance:

The study's findings are relevant to ALS research and clinical practice because they provide evidence that plasma isomiRs can be used to predict survival in ALS patients. The identified isomiR, let-7g-5p.t, has prognostic utility comparable to that of established biomarkers, such as neurofilament light chain (NfL) and miR-181. This suggests that plasma isomiRs could be used as a novel class of biomarkers for ALS, potentially refining prognostication in clinical trials and improving patient outcomes.

Items of the text and their relationships:

  1. Background: The text provides context on ALS and isomiRs, explaining that while isomiRs have distinct biological and clinical relevance, their potential as cell-free biomarkers in neurodegeneration remains largely unexplored.
  2. Method: The researchers used next-generation sequencing and two orthogonal statistical approaches to investigate the prognostic utility of plasma isomiRs in ALS.
  3. Findings: The study identified higher levels of let-7g-5p.t in ALS patients, which was associated with longer survival and independently validated in an international ALS cohort.
  4. Conclusion: The results establish isomiRs as a novel class of blood-based biomarkers in ALS, with potential to refine prognostication in clinical trials for neurodegenerative diseases.

Usefulness for disease management or drug discovery:

The study's findings are useful for disease management and drug discovery because they:

  1. Provide new biomarkers: The identified isomiR, let-7g-5p.t, can be used as a biomarker for ALS, potentially improving prognostication and patient outcomes.
  2. Inform treatment strategies: The study's findings can inform the development of new treatment strategies for ALS, such as targeted therapies that modulate the expression of isomiRs.

Originality:

The study provides original information beyond the obvious because it:

  1. Investigates a novel biomarker: The study investigates the use of plasma isomiRs as biomarkers for ALS, which is a new area of research.
  2. Provides evidence: The study provides evidence that plasma isomiRs can be used to predict survival in ALS patients, which is a significant finding in the field of neurodegenerative diseases.

Comparison with the state of art:

The study's findings are comparable to existing biomarkers for ALS, such as neurofilament light chain (NfL) and miR-181. However, the study's focus on plasma isomiRs as biomarkers for ALS is a new area of research that contributes to our understanding of the potential utility of isomiRs in neurodegenerative diseases.

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