Redefining Health Care Data Interoperability: Empirical Exploration of Large Language Models in Information Exchange.

BACKGROUND: Efficient data exchange and health care interoperability are impeded by medical records often being in nonstandardized or unstructured natural language format. Advanced language models, such as large language models (LLMs), may help overcome current challenges in information exchange. OBJECTIVE: This study aims to evaluate the capability of LLMs in transforming and transferring health care data to support interoperability. METHODS: Using data from the Medical Information Mart for Intensive Care III and UK Biobank, the study conducted 3 experiments. Experiment 1 assessed the accuracy of transforming structured laboratory results into unstructured format. Experiment 2 explored the conversion of diagnostic codes between the coding frameworks of the ICD-9-CM (International Classification of Diseases, Ninth Revision, Clinical Modification), and Systematized Nomenclature of Medicine Clinical Terms (SNOMED-CT) using a traditional mapping table and a text-based approach facilitated by the LLM ChatGPT. Experiment 3 focused on extracting targeted information from unstructured records that included comprehensive clinical information (discharge notes). RESULTS: The text-based approach showed a high conversion accuracy in transforming laboratory results (experiment 1) and an enhanced consistency in diagnostic code conversion, particularly for frequently used diagnostic names, compared with the traditional mapping approach (experiment 2). In experiment 3, the LLM showed a positive predictive value of 87.2% in extracting generic drug names. CONCLUSIONS: This study highlighted the potential role of LLMs in significantly improving health care data interoperability, demonstrated by their high accuracy and efficiency in data transformation and exchange. The LLMs hold vast potential for enhancing medical data exchange without complex standardization for medical terms and data structure.

What Proportion of BRCA-Associated Breast Cancer Is Human Epidermal Growth Factor 2-Low and Eligible for Additional Targeted Therapy?

INTRODUCTION: DESTINY B04 provided clinical meaning to a new classification of human epidermal growth factor 2 (HER2) expression in breast cancer: HER2-low. Patients with germline breast cancer type 1 gene pathogenic variants (gBRCA1) often develop triple negative breast cancer (TNBC), but the proportion who could be classified as HER2-low and qualify for an additional targeted therapy option is unknown. This study aims to characterize the proportion of gBRCA1 or germline breast cancer type 2 gene pathogenic variants patients for whom these novel targeted therapies may be an option. METHODS: We performed a retrospective chart review of patients with gBRCA1/2 treated at our institution for invasive breast cancer from 2000 to 2021. Synchronous or metachronous contralateral breast cancers were recorded separately. HER2 status was determined by immunohistochemistry and fluorescence in situ hybridization. We excluded patients without complete HER2 data. RESULTS: Among the 95 breast cancers identified in our cohort of 85 gBRCA1/2 patients, 41 (43%) were TNBC, 38 (40%) were hormone receptor positive (HR+)/HER2-negative, and 16 (17%) were HER2-positive based on standard conventions. We found that 82% of the HR+/HER2-cancers and 66% of TNBCs would be reclassified as HER2-low. After stratifying by BRCA gene status, 64% of cancers in patients with gBRCA1 and 58% of cancers in patients with germline breast cancer type 2 gene pathogenic variants were HER2-low. CONCLUSIONS: A significant portion of gBRCA1/2 patients who were previously diagnosed with TNBC or HR+/HER2- breast cancer would now be classified as HER2-low and could be considered for the use of trastuzumab deruxtecan in the metastatic setting. Outcome differences from therapy changes in this cohort should now be assessed.

Non-flammable Gel Polymer Electrolyte for Enhancing the Safety and High-Temperature Performance of Lithium-Ion Batteries.

As the applications of lithium-ion batteries (LIBs) have expanded, battery safety has emerged as a major concern because of the thermal runaway of LIBs arising from the use of flammable liquid electrolytes (LEs). Gel polymer electrolytes (GPEs) have been considered as potential candidates to replace LEs and improve the thermal safety of LIBs. In our study, a chemically cross-linked nonflammable GPE was synthesized and used in an LIB. A cross-linking agent, spirocyclic pentaerythritol diphosphate perfluorinated ether acrylate, comprising a phosphorus moiety and a fluoroether chain, was designed and synthesized to prepare a nonflammable cross-linked GPE. The obtained GPE effectively suppressed the deleterious reactions of the LE and imparted nonflammable characteristics. The pouch-type graphite/LiNi0.6Co0.2Mn0.2O2 cell with a nonflammable GPE delivered an initial discharge capacity of 146.7 mAh g-1 with a capacity retention of 71.1% after 300 cycles at 0.5 C and 55 °C. Moreover, the chemically cross-linked GPE exhibited excellent dimensional and thermal stability, which allowed for the safer operation of LIBs even under harsh conditions. This work provides guidelines for designing nonflammable electrolyte systems for advanced LIBs with high safety, enhanced thermal stability, and good cycling characteristics at elevated temperatures.

Correction to "Electrical and Thermal Properties of Surface-Modified Copper Nanowire/Polystyrene Nanocomposites through Latex Blending".

[This corrects the article DOI: 10.1021/acsomega.3c06775.].

Evaluation of GPT-4 for 10-year cardiovascular risk prediction: Insights from the UK Biobank and KoGES data.

Cardiovascular disease (CVD) remains a pressing global health concern. While traditional risk prediction methods such as the Framingham and American College of Cardiology/American Heart Association (ACC/AHA) risk scores have been widely used in the practice, artificial intelligence (AI), especially GPT-4, offers new opportunities. Utilizing large scale of multi-center data from 47,468 UK Biobank participants and 5,718 KoGES participants, this study quantitatively evaluated the predictive capabilities of GPT-4 in comparison with traditional models. Our results suggest that the GPT-based score showed commendably comparable performance in CVD prediction when compared to traditional models (AUROC on UKB: 0.725 for GPT-4, 0.733 for ACC/AHA, 0.728 for Framingham; KoGES: 0.664 for GPT-4, 0.674 for ACC/AHA, 0.675 for Framingham). Even with omission of certain variables, GPT-4's performance was robust, demonstrating its adaptability to data-scarce situations. In conclusion, this study emphasizes the promising role of GPT-4 in predicting CVD risks across varied ethnic datasets, pointing toward its expansive future applications in the medical practice.

Integration of National Health Insurance claims data and animal models reveals fexofenadine as a promising repurposed drug for Parkinson's disease.

BACKGROUND: Parkinson's disease (PD) is a common and costly progressive neurodegenerative disease of unclear etiology. A disease-modifying approach that can directly stop or slow its progression remains a major unmet need in the treatment of PD. A clinical pharmacology-based drug repositioning strategy is a useful approach for identifying new drugs for PD. METHODS: We analyzed claims data obtained from the National Health Insurance Service (NHIS), which covers a significant portion of the South Korean population, to investigate the association between antihistamines, a class of drugs commonly used to treat allergic symptoms by blocking H1 receptor, and PD in a real-world setting. Additionally, we validated this model using various animal models of PD such as the 6-hydroxydopmaine (6-OHDA), α-synuclein preformed fibrils (PFF) injection, and Caenorhabditis elegans (C. elegans) models. Finally, whole transcriptome data and Ingenuity Pathway Analysis (IPA) were used to elucidate drug mechanism pathways. RESULTS: We identified fexofenadine as the most promising candidate using National Health Insurance claims data in the real world. In several animal models, including the 6-OHDA, PFF injection, and C. elegans models, fexofenadine ameliorated PD-related pathologies. RNA-seq analysis and the subsequent experiments suggested that fexofenadine is effective in PD via inhibition of peripheral immune cell infiltration into the brain. CONCLUSION: Fexofenadine shows promise for the treatment of PD, identified through clinical data and validated in diverse animal models. This combined clinical and preclinical approach offers valuable insights for developing novel PD therapeutics.

Exploring the Cathode Active Materials for Sulfide-Based All-Solid-State Lithium Batteries with High Energy Density.

All-solid-state lithium batteries (ASSLBs) are considered promising alternatives to current lithium-ion batteries that employ liquid electrolytes due to their high energy density and enhanced safety. Among various types of solid electrolytes, sulfide-based electrolytes are being actively studied, because they exhibit high ionic conductivity and high ductility, which enable good interfacial contacts in solid electrolytes without sintering at high temperatures. To improve the energy density of the sulfide-based ASSLBs, it is essential to increase the loading of active material in the composite cathode. In this study, the Ni-rich LiNix Coy Mn1-x-y O2 (NCM) materials are explored with different Ni content, particle size, and crystalline form to probe suitable cathode active materials for high-performance ASSLBs with high energy density. The results reveal that single-crystalline LiNi0.82 Co0.10 Mn0.08 O2 material with a small particle size exhibits the best cycling performance in the ASSLB assembled with a high mass loaded cathode (active mass loading: 26 mg cm-2 , areal capacity: 5.0 mAh cm-2 ) in terms of discharge capacity, capacity retention, and rate capability.

Electrical and Thermal Properties of Surface-Modified Copper Nanowire/Polystyrene Nanocomposites through Latex Blending.

The incorporation of conductive nanofillers into an insulating polymer matrix commonly leads to nanocomposites with good electrical, thermal, and mechanical properties. In this study, copper nanowires (CuNWs) and polystyrene (PS) microspheres were synthesized along with the fabrication of CuNW/PS polymer nanocomposites. The electrical, thermal, mechanical, rheological, and morphological properties of the CuNW/PS nanocomposites were examined. The CuNWs were homogeneously dispersed in the PS matrix through latex blending. For the CuNW/PS nanocomposites, the storage modulus was higher than the loss modulus at all frequencies, indicating their elastic-dominant behavior. The electrical and thermal conductivities of the nanocomposites increased with an increasing CuNW content. Using a mixed dispersion of two monodisperse PS particles of 500 nm and 5 µm in diameter resulted in the highest electrical conductivity (ca. 10° S/m for 30 wt % nanofillers) among the nanocomposites. In addition, the introduction of silica- and polydopamine-coated CuNWs as nanofillers imparted insulation properties to the nanocomposites, with electrical conductivities to 10-10-10-8 S/m. When using 500 nm PS particles, the thermal conductivity of the surface-modified CuNW/PS nanocomposite at 30 wt % of CuNW was enhanced to 0.22 W/m·K compared to 0.17 W/m·K for its unmodified counterpart. We have achieved multiple innovative approaches, including the use of mixed particle sizes, surface modification of CuNW, and the exploration of elastic-dominant behavior. This enhanced thermal conductivity, coupled with the attainment of insulation properties, presents a distinct advantage for thermal interface material (TIM) applications.

Variability of Transrectal Shear Wave Elastography in a Phantom Model.

Purpose: This study aimed to assess the variability of transrectal shear wave elastography (SWE) using a designed phantom. Materials and Methods: In a phantom, the SWE values were examined by two radiologists using agarose and emulsion silicone of different sizes (1, 2, and 3 cm) and shapes (round, cubic) at three depths (1, 2, and 3 cm), two region of interest (ROI) and locations (central, peripheral) using two ultrasound machines (A, B from different vendors). Variability was evaluated using the coefficient of variation (CV). Results: The CVs decreased with increasing phantom size. Significant changes in SWE values included; agarose phantom at 3 cm depth (p < 0.001; machine A), 1 cm depth (p = 0.01; machine B), emulsion silicone at 2 cm depth (p = 0.047, p = 0.020; both machines). The CVs increased with increasing depth. Significant changes in SWE values included; 1 cm agarose (p = 0.037, p = 0.021; both machines) and 2 cm agarose phantom (p = 0.047; machine A). Significant differences in SWE values were observed between the shapes for emulsion silicone phantom (p = 0.032; machines A) and between ROI locations on machine B (p ≤ 0.001). The SWE values differed significantly between the two machines (p < 0.05). The intra-/inter-operator agreements were excellent (intraclass correlation coefficient > 0.9). Conclusion: The phantom size, depth, and different machines affected the variability of transrectal SWE.

A clock-dependent brake for rhythmic arousal in the dorsomedial hypothalamus.

Circadian clocks generate rhythms of arousal, but the underlying molecular and cellular mechanisms remain unclear. In Drosophila, the clock output molecule WIDE AWAKE (WAKE) labels rhythmic neural networks and cyclically regulates sleep and arousal. Here, we show, in a male mouse model, that mWAKE/ANKFN1 labels a subpopulation of dorsomedial hypothalamus (DMH) neurons involved in rhythmic arousal and acts in the DMH to reduce arousal at night. In vivo Ca2+ imaging reveals elevated DMHmWAKE activity during wakefulness and rapid eye movement (REM) sleep, while patch-clamp recordings show that DMHmWAKE neurons fire more frequently at night. Chemogenetic manipulations demonstrate that DMHmWAKE neurons are necessary and sufficient for arousal. Single-cell profiling coupled with optogenetic activation experiments suggest that GABAergic DMHmWAKE neurons promote arousal. Surprisingly, our data suggest that mWAKE acts as a clock-dependent brake on arousal during the night, when mice are normally active. mWAKE levels peak at night under clock control, and loss of mWAKE leads to hyperarousal and greater DMHmWAKE neuronal excitability specifically at night. These results suggest that the clock does not solely promote arousal during an animal's active period, but instead uses opposing processes to produce appropriate levels of arousal in a time-dependent manner.

Interaction of chlorothalonil and Varroa destructor on immature honey bees rearing in vitro.

Under realistic environmental conditions, bees are often exposed to multiple stressors, especially Varroa destructor and pesticides. In this study, the effects of exposure to NOAEC of chlorothalonil during the larval stage, in the presence or absence of V. destructor, was examined in terms of survival, morphological and transcriptional changes. The interaction between chlorothalonil and V. destructor on the survival of honey bee was additive. V. destructor are the dominant factor in the interaction for survival and transcriptome alternation. The downregulation of the genes related to tissue growth and caste differentiation may directly link to the mortality of honey bees. Either chlorothalonil or V. destructor induces the irregular morphology of trophocytes and oenocytes in the fat body. In addition to irregular shapes, oenocytes in V. destructor alone and double-stressor treatment group showed altered nuclei and vacuoles in the cytoplasm. The interaction of V. destructor and chlorothalonil at the larval stage have potential adverse effects on the subsequent adult bees, with up-regulation of genes involved in lipid metabolism and detoxification/defense in fat body tissue. Our findings provide a comprehensive understanding of combinatorial effects between biotic and abiotic stressors on one of the most important pollinators, honey bees.

Solid Hybrid Electrolyte Featuring a Vertically Aligned Li6.4La3.0Zr1.4Ta0.6O12 Membrane for All-Solid-State Lithium Batteries.

All-solid-state lithium batteries (ASSLBs) with enhanced safety are considered one of the most promising substitutes for liquid electrolyte-based Li-ion batteries. However, many properties of solid electrolytes, such as ionic conductivity, film formability, and electrochemical, mechanical, thermal, and interfacial stability need to be improved for their practical application. In this study, a vertically aligned Li6.4La3.0Zr1.4Ta0.6O12 (LLZO) membrane with finger-like microvoids was prepared using processes involving phase inversion and sintering. A hybrid electrolyte was then obtained by infusing the LLZO membrane with a solid polymer electrolyte based on poly(ε-caprolactone). The solid hybrid electrolyte (SHE) was a flexible thin film with high ionic conductivity, superior electrochemical stability, high Li+ transference number, enhanced thermal stability, and improved Li metal electrode-solid electrolyte interfacial stability. A solid-state Li/LiNi0.78Co0.10Mn0.12O2 cell assembled with the hybrid electrolyte exhibited good cycling performance, in terms of discharge capacity, cycling stability, and rate capability. Accordingly, the SHE using a vertically aligned LLZO membrane is a promising solid electrolyte for realizing safe, high-performance ASSLBs.

A super Sonic circadian synchronizer.

Sonic Hedgehog signaling and primary cilia control the core mammalian circadian clock.

3D Porous Oxygen-Doped and Nitrogen-Doped Graphitic Carbons Derived from Metal Azolate Frameworks as Cathode and Anode Materials for High-Performance Dual-Carbon Sodium-Ion Hybrid Capacitors.

Sodium-ion hybrid capacitors (SIHCs) in principle can utilize the advantages of batteries and supercapacitors and satisfy the cost demand of large-scale energy storage systems, but the sluggish kinetics and low capacities of its anode and cathode are yet to be overcome. Here, a strategy is reported to realize high-performance dual-carbon SIHCs using 3D porous graphitic carbon cathode and anode materials derived from metal-azolate framework-6s (MAF-6s). First, MAF-6s, with or without urea loading, are pyrolyzed to synthesize MAF-derived carbons (MDCs). Then, cathode materials are synthesized via the controlled KOH-assisted pyrolysis of MDCs (K-MDCs). K-MDCs, 3D graphitic carbons, resulting in a record-high surface area (5214 m2  g-1 ) being ≈four-fold higher than pristine MAF-6, oxygen-doped sites for high capacity, rich mesopores affording fast ion transport, and high capacity retention over 5000 charge/discharge cycles. Moreover, 3D porous MDC anode materials are synthesized from N-containing MAF-6 and exhibited to allow cycle stability over 5000 cycles. Furthermore, dual-carbon MDC//K-MDC SIHCs with different loadings (3 to 6 mg cm-2 ) are demonstrated to achieve high energy densities exceeding those of sodium-ion batteries and supercapacitors. Additionally, it allows an ultrafast-chargeable high power density of 20000 W kg-1 and robust cycle stability overcoming those of a typical battery.

Honey Bee Colonies (Apis mellifera L.) Perform Orientation Defensiveness That Varies among Bred Lines.

Honey bees (Apis mellifera L.) express complex behavioral patterns (aggressiveness) in defensive mechanisms for their survival. Their phenotypic expression of defensive behavior is influenced by internal and external stimuli. Knowledge of this behavior has recently become increasingly important, though beekeepers are still faced with the challenges of selecting defensive and less-defensive bred lines. Field evaluation of defensive behavior among bred lines of honey bees is required to overcome the challenges. Chemical cues (alarm pheromone and isopentyl acetate mixed with paraffin oil) and physical and visual stimuli (dark leather suede, colony marbling, and suede jiggling) were used to evaluate defensiveness and orientation among five bred lines of honeybee colonies. Our results showed that both chemical assays recruited bees, but the time of recruitment was significantly faster for alarm pheromone. Honeybees' response to both assays culminated in stings that differed among bred lines for alarm pheromone and paraffin when colonies were marbled. Honeybee orientation defensiveness varied among bred lines and was higher in more defensive bred lines compared to less-defensive bred lines. Our findings suggest that it is crucial to repeatedly evaluate orientation defensiveness at the colony level and among bred lines when selecting breeding colonies.

Synthetic maize centromeres transmit chromosomes across generations.

Centromeres are long, often repetitive regions of genomes that bind kinetochore proteins and ensure normal chromosome segregation. Engineering centromeres that function in vivo has proven to be difficult. Here we describe a tethering approach that activates functional maize centromeres at synthetic sequence arrays. A LexA-CENH3 fusion protein was used to recruit native Centromeric Histone H3 (CENH3) to long arrays of LexO repeats on a chromosome arm. Newly recruited CENH3 was sufficient to organize functional kinetochores that caused chromosome breakage, releasing chromosome fragments that were passed through meiosis and into progeny. Several fragments formed independent neochromosomes with centromeres localized over the LexO repeat arrays. The new centromeres were self-sustaining and transmitted neochromosomes to subsequent generations in the absence of the LexA-CENH3 activator. Our results demonstrate the feasibility of using synthetic centromeres for karyotype engineering applications.

Lower limb muscle matters in patients with hypoxic brain injury following out-of-hospital cardiac arrest.

BACKGROUND: There are conflicting results regarding the association between body mass index and the prognosis of cardiac arrest patients. We investigated the association of the composition and distribution of muscle and fat with neurologic outcomes at hospital discharge in successfully resuscitated out-of-hospital cardiac arrest (OHCA) patients. METHODS: This prospective, single-centre, observational study involved adult OHCA patients, conducted between April 2019 and June 2021. The ratio of total skeletal muscle, upper limb muscle, lower limb muscle, and total fat to body weight was measured using InBody S10, a bioimpedance analyser, after achieving the return of spontaneous circulation. Restricted cubic spline curves with four knots were used to examine the relationship between total skeletal muscle, upper limb muscle, and lower limb muscle relative to total body weight and neurologic outcome at discharge. Multivariable logistic regression analysis was performed to assess an independent association. RESULTS: A total of 66 patients were enrolled in the study. The proportion of total muscle and lower limb muscle positively correlated with the possibility of having a good neurologic outcome. The proportion of lower limb muscle showed an independent association in the multivariable analysis (adjusted odds ratio, 2.29; 95% confidence interval, 1.06-13.98), and its optimal cut-off value calculated through receiver operating characteristic curve analysis was 23.1%, which can predict a good neurological outcome. CONCLUSIONS: A higher proportion of lower limb muscle to body weight was independently associated with the probability of having a good neurologic outcome in OHCA patients.

Flyways and migratory behaviour of the Vega gull (Larus vegae), a little-known Arctic endemic.

Large gulls are generalist predators that play an important role in Arctic food webs. Describing the migratory patterns and phenology of these predators is essential to understanding how Arctic ecosystems function. However, from all six large Arctic gull taxa, including three long-distance migrants, to date seasonal movements have been studied only in three and with small sample sizes. To document the flyways and migratory behaviour of the Vega gull, a widespread but little-studied Siberian migrant, we monitored 28 individuals with GPS loggers over a mean period of 383 days. Birds used similar routes in spring and autumn, preferring coastal to inland or offshore routes, and travelled 4000-5500 km between their breeding (Siberia) and wintering grounds (mainly the Republic of Korea and Japan). Spring migration mainly occurred in May, and was twice as fast and more synchronized among individuals than autumn migration. Migration bouts mainly occurred during the day and twilight, but rates of travel were always higher during the few night flights. Flight altitudes were nearly always higher during migration bouts than during other bouts, and lower during twilight than during night or day. Altitudes above 2000m were recorded during migrations, when birds made non-stop inland flights over mountain ranges and vast stretches of the boreal forest. Individuals showed high inter-annual consistency in their movements in winter and summer, indicating strong site fidelity to their breeding and wintering sites. Within-individual variation was similar in spring and autumn, but between individual variation was higher in autumn than in spring. Compared to previous studies, our results suggest that the timing of spring migration in large Arctic gulls is likely constrained by snowmelt at breeding grounds, while the duration of migration windows could be related to the proportion of inland versus coastal habitats found along their flyways ('fly-and-forage' strategy). Ongoing environmental changes are hence likely in short term to alter the timing of their migration, and in long term possibly affect the duration if e.g. the resource availability along the route changes in the future.

A neuroepithelial wave of BMP signalling drives anteroposterior specification of the tuberal hypothalamus.

The tuberal hypothalamus controls life-supporting homeostatic processes, but despite its fundamental role, the cells and signalling pathways that specify this unique region of the central nervous system in embryogenesis are poorly characterised. Here, we combine experimental and bioinformatic approaches in the embryonic chick to show that the tuberal hypothalamus is progressively generated from hypothalamic floor plate-like cells. Fate-mapping studies show that a stream of tuberal progenitors develops in the anterior-ventral neural tube as a wave of neuroepithelial-derived BMP signalling sweeps from anterior to posterior through the hypothalamic floor plate. As later-specified posterior tuberal progenitors are generated, early specified anterior tuberal progenitors become progressively more distant from these BMP signals and differentiate into tuberal neurogenic cells. Gain- and loss-of-function experiments in vivo and ex vivo show that BMP signalling initiates tuberal progenitor specification, but must be eliminated for these to progress to anterior neurogenic progenitors. scRNA-Seq profiling shows that tuberal progenitors that are specified after the major period of anterior tuberal specification begin to upregulate genes that characterise radial glial cells. This study provides an integrated account of the development of the tuberal hypothalamus.