A New Deep State-Space Analysis Framework for Patient Latent State Estimation and Classification from EHR Time Series Data

Many diseases, including cancer and chronic conditions, require extended treatment periods and long-term strategies. Machine learning and AI research focusing on electronic health records (EHRs) have emerged to address this need. Effective treatment strategies involve more than capturing sequential changes in patient test values. It requires an explainable and clinically interpretable model by capturing the patient's internal state over time. In this study, we propose the "deep state-space analysis framework," using time-series unsupervised learning of EHRs with a deep state-space model. This framework enables learning, visualizing, and clustering of temporal changes in patient latent states related to disease progression. We evaluated our framework using time-series laboratory data from 12,695 cancer patients. By estimating latent states, we successfully discover latent states related to prognosis. By visualization and cluster analysis, the temporal transition of patient status and test items during state transitions characteristic of each anticancer drug were identified. Our framework surpasses existing methods in capturing interpretable latent space. It can be expected to enhance our comprehension of disease progression from EHRs, aiding treatment adjustments and prognostic determinations.Comment: 21 pages, 6 figure

Malignant transformation of central neurocytoma with dissemination 17 years after initial treatment: illustrative case

BACKGROUND: Central neurocytomas usually have a favorable clinical course, and gross total resection (GTR) results in long-term survival. Recurrences of central neurocytomas are usually local, and dissemination is extremely rare. OBSERVATIONS: A 24-year-old man who presented with vomiting was found to have a mass in the right lateral ventricle. After GTR, he received whole-brain irradiation and chemotherapy and had remained disease-free on follow-up for years. The review of the initial tumor revealed central neurocytoma. Seventeen years later, he presented with deterioration of memory, and magnetic resonance imaging showed an enhanced lesion in the left hippocampus. The enhanced lesion was resected, and the histological examination revealed that the tumor was a disseminated atypical central neurocytoma with frequent mitoses. Although he was treated with chemotherapy, the disseminated tumor slowly grew and invaded the brain. Massive brain invasion occurred without enhanced lesions, and he died 27 months after the tumor recurrence. LESSONS: In this patient, a central neurocytoma disseminated after an extremely long period of time. Once neurocytomas disseminate and show aggressive behavior, patients usually follow a poor course. Patients with central neurocytomas should be followed up for a long time

Regression of Necrotic Lesions after Methotrexate Withdrawal in Patients with Methotrexate-Associated Lymphoproliferative Disorders: A Retrospective CT Study

This retrospective study investigated whether necrotic lesions detected on a computed tomography (CT) scan are more regressive than non-necrotic lesions after methotrexate withdrawal in patients pathologically diagnosed with methotrexate-associated lymphoproliferative disorders (MTX-LPD). In total, 89 lesions extracted from 24 patients on CT scans were included in the analysis. All patients had been evaluated for the presence of necrosis within lesions via CT scan upon first suspicion of MTX-LPD (baseline CT scan). The percentage lesion size reduction between the baseline and initial follow-up CT scan was calculated. The association between necrosis within lesions and size changes was estimated via linear regression analyses using both crude and adjusted models. Necrosis was significantly more common in extranodal lesions (27 out of 30 lesions, 90%) than in nodal lesions (9 out of 59 lesions, 15%, p<0.001). In the crude model, the regression of necrotic lesions was 58.5% greater than that of non-necrotic lesions; the difference was statistically significant (p<0.001). Additionally, the longest diameter of necrotic lesions at the baseline CT scan was significantly greater than that of non-necrotic lesions (p<0.001). Based on the adjusted model, necrotic lesions showed 49.3% greater regression than non-necrotic lesions (p=0.017). Necrosis detected on a CT scan was found to be an independent predictor of regression after MTX withdrawal in patients with MTX-LPD

Induced-fit expansion and contraction of a self-assembled nanocube finely responding to neutral and anionic guests

Induced-fit or conformational selection is of profound significance in biological regulation. Biological receptors alter their conformation to respond to the shape and electrostatic surfaces of guest molecules. Here we report a water-soluble artificial molecular host that can sensitively respond to the size, shape, and charged state of guest molecules. The molecular host, i.e. nanocube, is an assembled structure consisting of six gear-shaped amphiphiles (GSAs). This nanocube can expand or contract its size upon the encapsulation of neutral and anionic guest molecules with a volume ranging from 74 to 535 Å3 by induced-fit. The responding property of this nanocube, reminiscent of a feature of biological molecules, arises from the fact that the GSAs in the nanocubes are connected to each other only through the hydrophobic effect and very weak intermolecular interactions such as van der Waals and cation-π interactions

Systematic Cys mutagenesis of FlgI, the flagellar P-ring component of Escherichia coli

The bacterial flagellar motor is embedded in the cytoplasmic membrane, and penetrates the peptidoglycan layer and the outer membrane. A ring structure of the basal body called the P ring, which is located in the peptidoglycan layer, is thought to be required for smooth rotation and to function as a bushing. In this work, we characterized 32 cysteine-substituted Escherichia coli P-ring protein FlgI variants which were designed to substitute every 10th residue in the 346 aa mature form of FlgI. Immunoblot analysis against FlgI protein revealed that the cellular amounts of five FlgI variants were significantly decreased. Swarm assays showed that almost all of the variants had nearly wild-type function, but five variants significantly reduced the motility of the cells, and one of them in particular, FlgI G21C, completely disrupted FlgI function. The five residues that impaired motility of the cells were localized in the N terminus of FlgI. To demonstrate which residue(s) of FlgI is exposed to solvent on the surface of the protein, we examined cysteine modification by using the thiol-specific reagent methoxypolyethylene glycol 5000 maleimide, and classified the FlgI Cys variants into three groups: well-, moderately and less-labelled. Interestingly, the well- and moderately labelled residues of FlgI never overlapped with the residues known to be important for protein amount or motility. From these results and multiple alignments of amino acid sequences of various FlgI proteins, the highly conserved region in the N terminus, residues 1–120, of FlgI is speculated to play important roles in the stabilization of FlgI structure and the formation of the P ring by interacting with FlgI molecules and/or other flagellar components

Occupied and unoccupied electronic structure of Na doped MoS2(0001)

The influence of sodium on the band structure of MoS2(0001) and the comparison of the experimental band dispersion with density functional theory show excellent agreement for the occupied states (angle-resolved photoemission) and qualitative agreement for the unoccupied states (inverse photoemission spectroscopy). Na-adsorption leads to charge transfer to the MoS2 surface causing an effect similar to n-type doping of a semiconductor. The MoS2 occupied valence band structure shifts rigidly to greater binding with little change in the occupied state dispersion. Likewise, the unoccupied states shift downward, approaching the Fermi level, yet the amount of the shift for the unoccupied states is greater than that of the occupied states, effectively causing a narrowing of the MoS2 bandgap

Photoinduced swing of a diarylethene thin broad sword shaped crystal:a study on the detailed mechanism

We report a swinging motion of photochromic thin broad sword shaped crystals upon continuous irradiation with UV light. By contrast in thick crystals, photosalient phenomena were observed. The bending and swinging mechanisms are in fact due to molecular size changes as well as phase transitions. The first slight bending away from the light source is due to photocyclization-induced surface expansion, and the second dramatic bending toward UV incidence is due to single-crystal-to-single-crystal (SCSC) phase transition from the original phase I to phase IIUV. Upon visible light irradiation, the crystal returned to phase I. A similar SCSC phase transition with a similar volume decrease occurred by lowering the temperature (phase IIItemp). For both photoinduced and thermal SCSC phase transitions, the symmetry of the unit cell is lowered; in phase IIUV the twisting angle of disordered phenyl groups is different between two adjacent molecules, while in phase IIItemp, the population of the phenyl rotamer is different between adjacent molecules. In the case of phase IIUV, we found thickness dependent photosalient phenomena. The thin broad sword shaped crystals with a 3 mu m thickness showed no photosalient phenomena, whereas photoinduced SCSC phase transition occurred. In contrast, large crystals of several tens of mu m thickness showed photosalient phenomena on the irradiated surface where SCSC phase transition occurred. The results indicated that the accumulated strain, between isomerized and non-isomerized layers, gave rise to the photosalient phenomenon