Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Deep phenotyping”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 487 records · Page 27Linked to original sources
PubMed2006

Reflections on the relationship between psychiatric genetics and psychiatric nosology.

Research advances in psychiatric genetics have raised expectations that genetic findings might lead to major breakthroughs in psychiatric nosology. The author reviews the plausibility of these claims. Four areas are addressed. First, it is argued that familial aggregation of a single putative psychiatric syndrome provides at best limited evidence for the validity of that syndrome. Second, both traditional and molecular genetic strategies can supply important insights into major diagnostic conundrums. However, evidence that one or a few individual genes impact on risk for two disorders is not likely to resolve definitively the nosologic relationship between the two syndromes. Third, while gene-based essentialist models for psychiatric disorders are conceptually appealing, they are not well supported empirically. Gene discovery in psychiatry is, on its own, unlikely to allow us to "carve nature at its joints," thereby validating categorical psychiatric diagnoses. Fourth, the project to ground "messy" psychiatric categories on the firm foundation of genes-as an archetypal natural kind-may be fundamentally flawed because the very concept of "the gene" as a discrete entity is itself increasingly in doubt. Whereas psychiatric genetics has and will continue to provide important insights into the etiology of psychiatric and substance use disorders, it is not likely alone to provide deep answers to the complex and multifaceted problems facing psychiatric nosology.

Biological Psychiatry↗
PubMed1998

14N electron spin-echo envelope modulation of the S = 3/2 spin system of the Azotobacter vinelandii nitrogenase iron-molybdenum cofactor.

Wild-type nitrogenase MoFe protein shows a deep 14N electron spin-echo envelope modulation (ESEEM) arising from a nitrogen nucleus (N1) coupled to the S = 3/2 spin system of the FeMo-cofactor of the MoFe protein. A previous ESEEM study on altered MoFe proteins generated by substitutions at the alpha-195-histidine position suggested that alpha-195-histidine provides a hydrogen bond to the FeMo-cofactor but is not the source of the 14N1 modulation [DeRose et al. (1995) Biochemistry 34, 2809-2814]. This study also raised the possibility of a correlation between ESEEM spectroscopic properties and the nitrogenase phenotype. We now report ESEEM studies on altered MoFe proteins with substitutions at residues alpha-96-arginine, alpha-359-arginine, and alpha-381-phenylalanine to (i) assign the first-shell hydrogen bonding as revealed by the 14N modulation; (ii) explore the mechanistic relevance of the ESEEM signatures to nitrogenase activity; and (iii) study microscopic changes within the polypeptide environment of the FeMo-cofactor. Present ESEEM data reveals that two kinds of 14N modulations are present in wild-type MoFe protein. A new 2-dimensional procedure for high-precision analysis of the ESEEM data of the MoFe proteins shows that the deep wild-type ESEEM modulation (denoted N1) has a hyperfine-coupling constant of Aiso = 1.05 MHz and nuclear quadrupole coupling parameters of e2qQ = 2.17 MHz, eta = 0.59; the other (denoted N2) has a smaller hyperfine coupling of Aiso = approximately 0.5 MHz and e2qQ = approximately 3.5 MHz, eta = approximately 0.4. The N2 ESEEM pattern is more obvious when unmasked by substitutions that result in the loss of the deep N1 modulation. Correlations of the ESEEM properties and catalytic activities of the altered MoFe proteins suggest that (i) the side chain of the alpha-359-arginine is the source of the deep ESEEM N1 modulation; (ii) one or both of the amide nitrogens of alpha-356-glycine/alpha-357-glycine are responsible for the weak N2 modulation; (iii) substitution of the nonpolar alpha-381-phenylalanine residue, as well as substitution of either the alpha-195-histidine or alpha-359-arginine residues, can eliminate the N1 interaction with FeMo-cofactor; and (iv) ESEEM can be used to detect slight reorientations of FeMo-cofactor within its polypeptide pocket, although the mechanistic relevance of the loss or perturbation of the hydrogen-bonding interactions between FeMo-cofactor and polypeptide environment has not yet been established.

Azotobacter vinelandii↗
PubMed2002

Neuropathologic variation in frontotemporal dementia due to the intronic tau 10(+16) mutation.

BACKGROUND: An increasing number of recently described tau mutations show considerable clinical heterogeneity. The assessment of this phenotypic variation is of vital importance in the differential diagnosis of neurodegenerative diseases. OBJECTIVE: To assess the neuropathologic heterogeneity in a comprehensive study of 12 brains with a tau mutation at exon 10(+16) (C-to-T) splice site from 9 families. METHODS: A comprehensive neuropathologic examination has been carried out, using a wide range of tau antibodies. RESULTS: All brains showed frontotemporal atrophy of varying severity and pallor of the pigmented nuclei of the brainstem. The histologic changes were more extensive to include other cortical areas, the deep gray matter, and the white matter. The hallmark histologic lesions were the tau-positive neuronal and glial inclusions. In neurons, these ranged from typical neurofibrillary tangles through well-circumscribed inclusions to diffuse cytoplasmic staining. This tau pathology was complemented by the presence of large, abnormal achromatic neurons, neuronal loss, astrocytosis, and superficial status spongiosus. CONCLUSION: The distribution, type, and severity of these histologic abnormalities varied not only from case to case but also within the same brain. These brains with a common tau mutation raise important differential diagnostic problems: cases in the past might have been misdiagnosed as corticobasal degeneration or even atypical Pick disease, disorders with similar, if not identical, phenotypic manifestations.

Adult↗
PubMed2003

MjK1, a K+ channel from M. jannaschii, mediates K+ uptake and K+ sensitivity in E. coli.

The methanogenic and hyperthermophilic deep-sea archaeon Methanococcus jannaschii has three putative K+ channels, MVP (Mj0139), MjK1 (Mj0138.1) and MjK2 (Mj1357). The physiological function of these K+ channels was examined in a viability assay, using the Escherichia coli mutant LB2003 (kup1, DeltakdpABC5, DeltatrkA). While MjK2 expression had no effects on the potassium-dependent phenotype of LB2003, MVP and MjK1 complemented the deficiency at a concentration of 1 mM KCl. In contrast to KcsA, MthK and MVP, MjK1 strongly affected host cell viability at 10 and 100 mM KCl. The toxic effects were less pronounced when growth media were supplemented with the K+ channel blocker BaCl2.

Amino Acid Sequence↗
PubMed2003

ATP-induced hexameric ring structure of the cyanobacterial circadian clock protein KaiC.

BACKGROUND: KaiA, KaiB and KaiC are cyanobacterial circadian clock proteins. KaiC contains two ATP/GTP-binding Walker's motif As, and mutations in these regions affect the clock oscillations. RESULTS: ATP induced the hexamerization of KaiC. The Km value for the ATP for the hexamerization was 1.9 micro m. Triphosphate nucleotides bound to the two Walker's motif As, and their binding functioned cooperatively for the hexamerization. An unhydrolysable substrate, 5'-adenylylimidodiphosphate (AMPPNP), also induced the hexamerization, indicating that nucleotide binding, but not its hydrolysis, is essential for the hexamerization. Mutations in each of the two Walker's motif As that affect the clock phenotype increased the Km value for ATP and inhibited the hexamerization. Thus, the KaiC hexamerization seems to be necessary for its clock function. The KaiC hexamer has the shape of a hexagonal pot with a diameter and height of approximately 100 A and with a relatively large cavity (73 A deep and 18-34 A wide) inside. This pot-shaped structure suggests that KaiC functions in a similar manner to F1-ATPase, helicase or ATP-dependent protease/chaperon, all of which have dynamic activities inside the central cavity of their hexameric rings. CONCLUSION: ATP-induced KaiC hexamerization is necessary for the clock function of KaiC.

Adenosine Triphosphate↗
PubMed2005

Migraine and cerebral white matter lesions: when to suspect cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL).

BACKGROUND: Patients with migraine are at an increased risk for white matter lesions, typically multiple, small, punctate hyperintensities in the deep or periventricular white matter, best observed on magnetic resonance imaging utilizing T2-weighted or FLAIR sequences. The underlying pathogenesis of white matter lesions in migraineurs is unknown, and the lesions are usually nonspecific and of unclear clinical significance. REVIEW SUMMARY: Often the presence of white matter lesions causes uncertainty for physicians and anxiety for patients and may lead to a variety of diagnostic tests and treatments. Occasionally, white matter lesions may represent a secondary cause for headaches such as CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy). CADASIL is underrecognized and underdiagnosed; it should be suggested by (i) 1 or more of recurrent subcortical ischemic strokes (especially before age 60 and in the absence of vascular risk factors), migraine (especially with aura, including atypical or prolonged auras) and/or early cognitive decline or subcortical dementia; (ii) bilateral, multifocal, T2/FLAIR hyperintensities in the deep white matter and periventricular white matter with lesions involving the anterior temporal pole, external capsule, basal ganglia, and/or pons; and (iii) an autosomal-dominant family history of migraine, early-onset stroke, or dementia. The clinical spectrum of CADASIL is broad, and there is a poor genotype-phenotype correlation. In certain individuals or families, migraine may be the only clinical manifestation. CONCLUSIONS: While the prevalence of nonspecific white matter lesions in migraineurs is increased, the white matter lesions may occasionally represent a secondary cause for headache such as CADASIL. Greater awareness of the unique clinical, neuroimaging, and pathologic features, as well as the availability of diagnostic genetic testing, should enhance the recognition and diagnosis of this fascinating condition.

Brain↗
PubMed1992

Cutaneous manifestations of the eosinophilia-myalgia syndrome.

We report the cutaneous manifestations of the eosinophilia-myalgia syndrome in 10 patients, with specific reference to their clinical course, histopathological features, and immunogenetic studies. Cutaneous manifestations could be classified into three groups: morphoea-like sclerosis, urticarial and papular lesions, and generalized sclerosis. Despite this polymorphic clinical presentation, the histopathological abnormalities in all cases were strikingly similar, and consisted of superficial and deep perivascular lymphocytic dermal infiltrates, mucin deposition, and fascial inflammation (often in the absence of sclerosis). Immunoperoxidase studies revealed increased numbers of factor XIIIa- and MAC 387-positive cells in the inflammatory infiltrate. Immunogenetic studies demonstrated that 77% (7/9) of patients possessed the HLA-DR3 or HLA-DR4 phenotypes. Mean follow-up of 24 months after discontinuation of L-tryptophan revealed the presence of persistent severe disabling disease in 30% of patients.

Adult↗
PubMed2006

Novel facultative anaerobic acidotolerant Telmatospirillum siberiense gen. nov. sp. nov. isolated from mesotrophic fen.

Three facultative anaerobic acidotolerant Gram-negative motile spirilla strains designated 26-4b1, 26-2 and K-1 were isolated from mesotrophic Siberian fen as a component of methanogenic consortia. The isolates were found to grow chemoorganotrophically on several organic acids and glucose under anoxic and low oxygen pressure in the dark, tolerant up to 5kPa of oxygen. At low oxygen supply, faint autotrophic growth on the H(2):CO(2) mixture was also observed. All three isolates were able to fix N(2). Major cellular fatty acids were 18:1 omega7c, 17:0 cyclopropane and 16:0. Phylogenetic analyses of the 16S rRNA gene sequences revealed that they formed a deep branch within the family Rhodospirillaceae of the Alphaproteobacteria with the highest similarity of 90.9-92.5% with members of genera Phaeospirillum and Magnetospirillum. Phylogenetic study of nifH (nitrogenase) and cbbL (RuBisCO) amino acid sequence identities confirmed that the new isolates represent a novel group. Based on the phylogenetic analyses and distinct phenotypic characteristics, we are of the opinion that strains 26-4b1, 26-2 and K-1 represent a new species of a novel genus for which the name Telmatospirillum siberiense gen. nov. sp. nov. is proposed.

Acids↗
PubMed1998

[Type I protein C deficiency caused by a novel protein C gene mutation].

OBJECTIVE: To study the phenotype and genotype of a thrombophilia family. METHODS: Antigens and activities of protein C, antithrombin III, protein S, plasminogen and activated protein C resistance were assayed in 13 members from four generations of the family. RESULTS: Type I protein C deficiency was revealed in 5 members including the 3 members with deep vein thrombosis. All the exons and intron/exon junctions of the protein C gene were amplified by PCR. No abnormal band was found in SSCP assay. DNA sequencing identified a novel mutation 3444C-->A in exon VI of protein C gene leading to His134Asn. This mutation erased a Hph I site. PCR/Hph I analysis demonstrated that 6 members including 5 protein C deficiency members had the same mutations. CONCLUSION: His134Asn is a novel mutation causing type I protein C deficiency.

Adolescent↗
PubMed2025

Exploring penetrance of clinically relevant variants in over 800,000 humans from the Genome Aggregation Database.

Incomplete penetrance, or absence of disease phenotype in an individual with a disease-associated variant, is a major challenge in variant interpretation. Studying individuals with apparent incomplete penetrance can shed light on underlying drivers of altered phenotype penetrance. Here, we investigate clinically relevant variants from ClinVar in 807,162 individuals from the Genome Aggregation Database (gnomAD), demonstrating improved representation in gnomAD version 4. We then conduct a comprehensive case-by-case assessment of 734 predicted loss of function variants in 77 genes associated with severe, early-onset, highly penetrant haploinsufficient disease. Here, we identify explanations for the presumed lack of disease manifestation in 701 of 734 variants (95%). Individuals with unexplained lack of disease manifestation in this set of disorders are rare, underscoring the need and power of deep case-by-case assessment presented here to minimize false assignments of disease risk, particularly in unaffected individuals with higher rates of secondary properties that result in rescue.

Humans↗
PubMed2000

The A -844G polymorphism in the PAI-1 gene is associated with a higher risk of venous thrombosis in factor V Leiden carriers.

Identification of combined genetic factors in factor V Leiden carriers is important for a more accurate risk assessment for venous thrombosis (VT). Among these individuals, we evaluated the role of polymorphisms of the plasminogen activator inhibitor-1 (PAI-1) gene in the thrombophilic phenotype. A total of 382 factor V Leiden carriers were included in the study. This population was divided into 3 groups. Group 1 (n=168) included individuals with a personal history of VT; group 2 (n=140) included individuals without personal VT but with a familial history of VT; and group 3 (n=74) included individuals without VT and with a fortuitous discovery of the factor V Leiden mutation. We compared the genotype distribution of 2 polymorphisms, A -844G and -675 4G/5G, located in the promoter region of the PAI-1 gene among these 3 groups of individuals. The A -844G allele frequency differed significantly among the 3 groups (P=0.048), the A allele being more frequent in patients who suffered from VT (61%) than in subjects without VT (52%, P=0.015), whereas no difference was observed between the 2 groups of asymptomatic individuals. The prevalence of genotype AA carriers was higher in patients with VT (38%) than in asymptomatic individuals (21%, P=0. 015), leading to an odds ratio of 1.74 (95% confidence interval, 1.3 to 3.8). Carrying the AA genotype conferred a risk of deep VT of 2. 08 (95% confidence interval, 1.28 to 3.40), whereas it did not seem to significantly influence the risk of pulmonary embolism. Concerning the -675 4G/5G polymorphism, no significant difference was observed among the 3 groups, the 4G allele frequency being 0.54 (in group 1), 0.49 (in group 2), and 0.45 (in group 3). These data suggest a role for the -A844G PAI-1 gene polymorphism in the thrombophilic phenotype of factor V Leiden carriers.

Adolescent↗
PubMed1986

The morphological spectrum of T-prolymphocytic leukaemia.

The morphology of the cells from 29 cases of T-prolymphocytic leukaemia (T-PLL) was studied by light (LM) and transmission electron microscopy (TEM) and was compared with that of 33 B-cell PLL. The membrane phenotype of T-PLL cells was T4+, T8- in two-thirds of the cases, others being T4- T8+ or T4+ T8+. Two morphological types of T-PLL were defined according to the nuclear features: regular (55% of cases) and irregular (45% of cases). T-PLL cells with a regular, round or oval, nuclear outline resembled B-PLL cells but had less abundant cytoplasm and a higher nucleo-cytoplasmic ratio. Irregular T-prolymphocytes displayed a distinct convoluted nucleus. A 'small-cell' variant of T-PLL was recognized by TEM in six cases in which the diagnosis was uncertain by LM. A characteristic of all types of T-prolymphocytes by LM was the presence of a deep basophilic cytoplasm which by TEM corresponded to clusters of ribosomes and endoplasmic reticulum. No differences in clinico-haematological features or membrane markers were apparent between the morphological types of T-PLL, although it was noted that the three T4- T8+ cases had irregular cells and four of the small cell variant were T3- T4+. TEM permits a more precise assessment of the cytoplasmic organelles and nucleolus than LM analysis and facilitates the distinction between T-PLL and other leukaemias with a mature T-cell phenotype, namely adult T-cell leukaemia/lymphoma. Sezary syndrome and T-chronic lymphocytic leukaemia.

Aged↗
PubMed2003

Candida albicans clades.

DNA fingerprinting with the complex probe Ca3 has revealed the following five Candida albicans clades: group I, group II, group III, group SA and group E. These groups exhibit geographical specificity. Group SA is relatively specific (i.e., highly enriched) to South Africa, group E is relatively specific to Europe, and group II is absent in the Southwest USA and South America. The maintenance of deep-rooted clades side by side in the same geographical locale and the apparent absence of subclade structure suggest little recombination between clades, but higher rates of recombination within clades. Exclusive 5-fluorocytosine resistance in the majority of group I isolates reinforces the above conclusions on recombination, and demonstrates that clades differ phenotypically. The ramifications of these findings with regard to pathogenesis are discussed. In particular, these findings lay to rest the idea that one strain represents all strains of C. albicans, support the need for a worldwide analysis of population structure and clade-specific phenotypic characteristics, and demonstrate that in the future, pathogenic characteristics must be analyzed in representatives from all five clades.

Candida albicans↗
PubMedDate not supplied

Angiogenesis and endometrial cancer.

Angiogenesis occurs more frequently in endometrial carcinomas developing against a background of endometrial atrophy rather than carcinomas arising from a hyperplastic endometrium. In some studies, angiogenesis is associated with unfavourable histopathological features, but not in others. In all studies, however, increased angiogenesis is related to poor prognosis. Vascular endothelial growth factor (VEGF) is the major stimulus for endothelial cell proliferation in endometrial carcinomas and is, therefore, associated with high angiogenesis. VEGF expression at the invading tumour front is 4-10 times higher than in the inner tumour areas and is significantly associated with poor prognosis, particularly within stage I endometrial disease. However, since its stimulating effect on endothelial cells is basically dependent on the presence of VEGF receptors, i.e. the flk-1(KDR), the detection of a functionally intact angiogenic pathway VEGF/flk-1 (KDR) is a more reliable and, indeed, independent prognostic parameter. The other angiogenic factor, thymidine phosphorylase (TP), is related to the adverse histopathological variables of the non endometrioid carcinomas, high tumour grade, deep myometrial invasion and advanced stage of disease, at least at the invading tumour front, and its prognostic significance is, therefore, limited. Furthermore, it is not directly related with increased angiogenesis. However, the simultaneous expression of high VEGF / high TP activity at the invading tumour front emerged as the most potent angiogenic phenotype in endometrial carcinomas, indicating that the two molecules are co-operating. Furthermore, a high TP activity in the stromal cells is associated with a high density of activated macrophages which further promotes endometrial tumour angiogenesis.

Animals↗
PubMed1996

Allograft vascular disease: comparison of heart and other grafted organs.

A striking resemblance exists between the vasculopathy in several different allografts. The arteriopathy of epicardial coronary arteries is diffuse, involving proximal, distal, and small branch segments in a generally concentric pattern of intimal thickening. Smooth muscle cells in a lipid- and glycosaminoglycan-rich matrix are the predominant components of this expanded intima. Varying amounts of collagen are present, more being present late posttransplant. A superficial and, to a lesser degree, deep, bandlike infiltrate of T cells and macrophages is uniformly present, although it is somewhat more prominent in early lesions as compared to more severely narrowed arteries from longer-term, susceptible grafts. The media is likewise altered by areas of lipid and glycosaminoglycan deposition associated with smooth muscle cell loss and phenotypic modulation. The media is altered in an outside-to-inside direction, with percolation of adventitial leukocytes into the outer media. Virtually all of the coronary features are seen in the medium to large arteries of liver, pancreas, and kidney allografts. Chronic rejection in lung allografts is manifest by obliterative bronchiolitis; vascular changes, although architecturally similar, are somewhat less common and result in less-severe luminal narrowing. The role of allograft vasculopathy in chronic lung rejection is thus less certain. A finding perhaps unique to epicardial coronary arteries of heart allografts is the presence of eccentric lesions more typical of native atherosclerosis. Many of the latter grafts probably have preexistent, undetected donor disease. Sequential evaluation of vascular changes is limited in human biopsy material by their general absence in endomyocardial or core liver needle specimens. Fortunately, vascular changes can be detected in some renal and pancreas core needle biopsies, and these findings may provide an avenue for monitoring the effectiveness of immunosuppressive therapy, antiviral or lipid-altering therapies, or modifications of smooth muscle cell proliferation and glycosaminoglycan deposition yet to be developed.

Heart Transplantation↗
PubMed1999

Taxonomic studies of extremely barophilic bacteria isolated from the Mariana Trench and description of Moritella yayanosii sp. nov., a new barophilic bacterial isolate.

We have isolated two strains of extremely barophilic bacteria from sediment collected from the world's deepest ocean floor in the Mariana Trench, Challenger Deep, at a depth of 10898m [Kato C, Li L, Nogi Y, Nakamura Y, Tamaoka J, Horikoshi K (1998) Appl Environ Microbiol 64:1510-1513]. One strain, DB21MT-2, was identified as a strain of Shewanella benthica, and the other strain, DB21MT-5, is closely affiliated with members of the genus Moritella on the basis of 16S rDNA sequence analysis. The hybridization values for DNA-DNA relatedness between DB21MT-5 and the Moritella reference strains were significantly lower than that accepted as the phylogenetic definition of a species. Based on this and other taxonomic differences, strain DB21MT-5 appears to represent a novel obligately barophilic deep-sea Moritella species. The name Moritella yaynanosii (JCM 10263) is proposed. This is the first proposed species of obligately barophilic bacteria of the genus Moritella.

Bacteria↗
PubMed2001

Dystonia: an update on genetics and treatment.

Recent years have seen many advances in our understanding of the genetics of the dystonias, with 13 loci identified to date. The DYT1 gene, which causes most cases of childhood-onset generalized primary dystonia, was cloned in 1997, and use of cell models has begun to unravel the role of its protein (torsinA) in both health and disease. Treatment of more severe dystonia has been a difficult area, with only limited success from medical therapies. Recently, there has been increasing interest in the use of globus pallidus deep brain stimulation and a number of reports have shown promising results.

Adult↗
PubMed2026

Development and Validation of Machine Learning Models for Predicting Early Cognitive Decline Using Home Sensor-Derived Behavioral Data: Sensors in-Home for Elder Wellbeing (SINEW) Cohort Study.

BACKGROUND: As the global population continues to age, the prevalence of geriatric conditions, including dementia and frailty, is also increasing. Early identification of individuals at an elevated risk of these conditions, such as those presenting with mild cognitive impairment (MCI) or prefrailty, can provide a critical window for prompt intervention aimed at preventing or reversing disease progression. To promote such early identification, there is a burgeoning interest in the use of digital sensor technology and predictive modeling. OBJECTIVE: This study aimed to use a continuous, home-based monitoring sensor system for older adults to distinguish those exhibiting normal aging from those with MCI, early dementia, prefrailty, or frailty, and to predict their transition from normal aging to one of these conditions. METHODS: This longitudinal cohort study will recruit 200 community-dwelling adults aged ≥65 years with normal cognition or MCI at baseline. A multi-sensor system will be installed in participants' homes, including passive infrared motion sensors, door contact sensors, bed sensors, medication box sensors, wearable activity bands, and Bluetooth proximity beacons. These devices will continuously capture spatiotemporal activity patterns, mobility indicators, sleep behaviors, and medication-taking routines. Annual assessments will include standardized cognitive tests (eg, Montreal Cognitive Assessment, Mini-Mental State Examination, Rey Auditory-Verbal Learning Test, digit span, Color Trails Test, semantic fluency, Stroop), frailty measures (modified Fried phenotype, gait speed, grip strength), mental health scales, sleep quality, and psychosocial indicators. Sensor-derived features-such as gait variability, activity regularity, sleep fragmentation, and medication adherence patterns-will be integrated with clinical data to develop supervised machine learning models. Planned approaches include logistic regression, random forests, gradient boosting, and deep learning. Model performance will be evaluated using cross-validation and independent test sets. Primary metrics will include area under the receiver operating characteristic curve, sensitivity, specificity, precision, recall, and F1-score. Models will be benchmarked against gold-standard clinical diagnoses and validated using temporal subsets of the dataset. RESULTS: Enrollment for this study started in November 2019 and will continue until March 2030. As of June 2025, we have enrolled 138 participants. Full data analysis has yet to begin. CONCLUSIONS: We aim to develop a reliable and effective sensor system for in-home use that will facilitate the early detection of cognitive and physical decline. In so doing, it will add to our current understanding of digital biomarkers. It is common for older adults to seek clinical intervention only when their cognitive impairment has already reached an advanced stage. The implementation of readily deployable sensor systems within community settings presents us with opportunities for prompt intervention, which holds the potential for delaying or reversing disease progression and allowing for a greater number of functional and meaningful years.

Humans↗