Classification of headache disorders is dependent on a subjective self-report from patients and its interpretation by physicians. We aimed to apply objective data-driven machine learning approaches ...to analyze patient-reported symptoms and test the feasibility of the automated classification of headache disorders. The self-report data of 2162 patients were analyzed. Headache disorders were merged into five major entities. The patients were divided into training (n = 1286) and test (n = 876) cohorts. We trained a stacked classifier model with four layers of XGBoost classifiers. The first layer classified between migraine and others, the second layer classified between tension-type headache (TTH) and others, and the third layer classified between trigeminal autonomic cephalalgia (TAC) and others, and the fourth layer classified between epicranial and thunderclap headaches. Each layer selected different features from the self-reports by using least absolute shrinkage and selection operator. In the test cohort, our stacked classifier obtained accuracy of 81%, sensitivity of 88%, 69%, 65%, 53%, and 51%, and specificity of 95%, 55%, 46%, 48%, and 51% for migraine, TTH, TAC, epicranial headache, and thunderclap headaches, respectively. We showed that a machine-learning based approach is applicable in analyzing patient-reported questionnaires. Our result could serve as a baseline for future studies in headache research.
Background and objective
We aimed to provide real-world data on the effectiveness of an anti-calcitonin gene-related peptide monoclonal antibody administered for treating migraine in Korean patients.
...Methods
We prospectively recruited patients with migraine who received galcanezumab treatment at a single university hospital from June 2020 to April 2021. The treatment response was assessed after three consecutive monthly injections. A 50% responder rate was evaluated based on ≥50% reduction in the number of moderate/severe headache days.
Results
Overall, 87 patients were included in the analysis. Most patients were women (83.9%). They had a mean age of 41.7 ± 12.3 years (range 17–72). Sixty-five patients (74.7%) had chronic migraine, 35 patients (40.2%) had a history of medication-overuse headache, and 32 patients (36.8%) were previously unresponsive to or found intolerable five classes of preventive medication. After three months of treatment, mean changes in numbers of monthly headache days, moderate/severe headache days, crystal clear days, and days of acute medication use were −7.2 ± 8.43, −4.3 ± 9.76, 7.3 ± 8.50, and −4.1 ± 7.93, respectively. The 50% responder rates were 58.3%, 44.2%, and 40.6% for patients with unsuccessful previous use of 0–1, 2–4, and 5 preventive medication classes, respectively. Headache Impact Test-6 and Migraine Disability Assessment Test scores also decreased (−4.4 ± 8.09 and −32.9 ± 77.04, respectively).
Conclusion
In our cohort, the effectiveness and safety of galcanezumab were comparable with those reported in clinical trials, whereas a higher response rate was observed in the difficult-to-treat patient subset than that reported in trials. We provide real-world evidence of galcanezumab treatment benefits in Asian patients with migraine.
With the demand for low‐power‐operating artificial intelligence systems, bio‐inspired memristor devices exhibit potential in terms of high‐density memory functions and the emulation of the synaptic ...dynamics of the human brain. The 2D material MXene attracts considerable interest for use in resistive‐switching memory and artificial synapse devices owing to its excellent physicochemical properties in memristor devices. However, few memristive and synaptic MXene devices that display increased switching performances are reported, with no significant results. Herein, the conductivity of MXene (Ti3C2Tx) is engineered via etching and oxidation to enhance the switching performance of the device. The exceptional properties of partially oxidized MXene memristors include large memory windows and low threshold biases, and the complex spike‐timing‐dependent plasticity synaptic rules are also emulated. The low threshold potential distribution, reliable retention time (104 s), and distinct resistance states with a high ON–OFF ratio (>104) are the main memory‐related features of this device. The experimentally determined switching potentials of the optimized device are also uniformly distributed, according to a statistical probability‐based approach. This investigation may promote the essential material properties for use in high‐density non‐volatile memory storage and artificial synapse systems in the field of innovative nanoelectronic devices.
Exquisite improvements are witnessed for MXene memristors. Conventional memory cells confront the demands of future data‐intensive computing applications. This sortation has led the research on constructing the memristors with novel 2D functional materials for advanced applications of next‐generation memory technology. MXene for high‐density computing and synapse functionality at low power (among all Ti3C2) with edge detection applicability are manifested.
Brain‐inspired electronics with multimodal signal processing have been investigated as the next‐generation semiconductor platforms owing to the limitations of von Neumann architecture, which limits ...data processing and energy consumption efficiencies. This study demonstrates the molecular reconfiguration of plasticity of artificial synaptic devices with tunable electric conductance based on molecular dynamics at the channel surfaces for realizing chemical multimodality. Carrier transport dynamics are adjusted using the density of trapped carriers for the molecular adsorption of HS in the MoSe2 channel, and the results are consistent with the molecular simulations. In molecular dynamics‐controlled devices, enhanced hysteresis enables the engineering of artificial neuroplasticity, mimicking the neurotransmitter release of biological synapses. Owing to the molecular reconfigurability of MoSe2 devices, the synaptic weights of excitatory and inhibitory synapse modes are significantly enhanced. Thus, this study can potentially contribute to the creation of the next generation of multimodal interfaces and artificial intelligence hardware realization.
Molecular adsorption at the surface of channels induces the pulling or repelling of carriers transferred across the 2D semiconductor channel, which enables bioinspired synaptic behavior owing to the trapping or de‐trapping of carriers. Molecularly reconfigurable surface engineering in MoSe2 FETs is employed to mimic and enhance the essential features of biological synapses using van der Waals interactions upon molecular adsorption.
Climate change is predicted to increase the frequency, intensity, and duration of extreme cold events in the mid-latitudes. However, although diabetes is one of the most critical metabolic diseases ...due to its high and increasing prevalence worldwide, few studies have investigated the short-term association between cold exposure and diabetes-related outcomes.
The aim of this study was to investigate the associations between cold spells and their characteristics (intensity, duration, and seasonal timing) and hospital admission and mortality due to diabetes.
This study used claims data from the National Health Insurance Service and cause-specific mortality data from Statistics Korea (2010–2019). Cold spells were defined as ≥2 consecutive days with a daily mean temperature lower than the region-specific 5th percentile during the cold season (November–March). Quasi-Poisson regressions combined with distributed lag models were used to assess the associations between exposures and outcomes in 16 regions across the Republic of Korea. Meta-analyses were conducted to pool the region-specific estimates.
Exposure to cold spells was associated with an increased risk of hospital admission relative risk (RR) = 1.45, 95% confidence interval (CI): 1.26, 1.66 and mortality (RR = 2.02, 95% CI: 1.37, 2.99) due to diabetes. The association between cold spells and hospital admission due to diabetes was stronger for cold spells that were more intense, longer, and occurred later during the cold season. The association between cold spells and diabetes-related mortality was stronger for more intense and longer cold spells.
This study emphasizes the importance of developing effective interventions against cold spells, including education on the dangers of cold spells and early alarm systems. Further studies are needed to create real-world interventions and evaluate their effectiveness in improving diabetes-related outcomes.
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•The short-term association between cold spells and diabetes has rarely been studied.•This time-series study used nationwide claims and cause-specific mortality data.•Cold spells were associated with diabetes-related hospitalization and mortality.•These associations were stronger for more intense and longer cold spells.•It is important to develop effective interventions against cold spells.
Emerging evidence supports an association between heat exposure and acute kidney injury (AKI). However, there is a paucity of studies on the association between cold exposure and AKI.
We aimed to ...investigate the associations of cold exposure with hospital admission and mortality due to AKI and to explore whether these associations were influenced by age and sex.
Information on daily counts of hospital admission and mortality due to AKI in 16 regions of Korea during the cold seasons (2010–2019) was obtained from the National Health Insurance Service (a single national insurer providing universal health coverage) and Statistics Korea. Daily mean temperature and relative humidity were calculated from hourly data obtained from 94 monitoring systems operated by the Korean Meteorological Administration. Associations of low temperatures (<10th percentile of daily mean temperature) and cold spells (≥2 consecutive days with <5th percentile of daily mean temperature) up to 21 days with AKI were estimated using quasi-Poisson regression models adjusted for potential confounders (e.g., relative humidity and air pollutants) with distributed lag models and univariate meta-regression models.
Low temperatures were associated with hospital admission due to AKI relative risk (RR) = 1.12, 95 % confidence interval (CI): 1.09, 1.16. Cold spells were associated with hospital admission (RR = 1.87, 95 % CI: 1.46, 2.39) and mortality due to AKI (RR = 4.84, 95 % CI: 1.30, 17.98). These associations were stronger among individuals aged ≥65 years than among those aged <65 years.
Our results underscore the need for the general population, particularly the elderly, physicians, and other healthcare providers to be more vigilant to cold exposure, given the risk of AKI. Government agencies need to develop specific strategies for the prevention and early detection of cold exposure-related AKI.
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•Low temperatures were associated with hospital admission due to acute kidney injury.•Cold spells were associated with hospital admission due to acute kidney injury.•Cold spells were also associated with mortality due to acute kidney injury.•These associations were stronger among individuals aged ≥65 years.
Ethanol intake can alter pharmacokinetics by increasing the solubility or enhancing the absorption of concomitant drugs. Here, a selective, sensitive and reproducible high‐performance liquid ...chromatography–tandem mass spectrometry method for the quantitative analysis of nicardipine in rat plasma was developed using simple protein precipitation. The calibration curve was linear over a concentration range of 1–2,000 ng/ml (r2 > 0.998). Accuracy ranged from 93.4 to 112.2% and precision was within 12.1% from three independent analytical batches. Stable conditions for the quantification of nicardipine in rat plasma were established in various conditions, including sample storage and handling. The matrix effect was negligible, and recovery was consistent at three different levels of quality control sample. The method was applied to assessment for the effect of ethanol on the pharmacokinetics of nicardipine in rats. The oral bioavailability of nicardipine was increased from 5.4 to 9.4% in Sprague–Dawley rats by concomitant oral administration of ethanol whereas the half‐life was not altered. The findings indicated that concomitant ethanol intake can increase systemic drug exposure by increasing gastrointestinal absorption, especially poorly soluble drugs. This study provides an insight for further investigation of the alteration of the pharmacological effect of poorly soluble drugs owing to ethanol intake.
•HPLC-MS/MS method for the simultaneous determination of PFOA and linear PFOS in human sera was developed and fully validated.•A sample preparation method was optimized by combining solid-phase ...extraction and protein precipitation.•Chromatographic separation of the linear PFOS from branched isomers was completely achieved.•Using 13C-labeled PFOA and PFOS as calibrators, the method overcame a lack of PFOA- and PFOS-free human serum.•The median concentration of linear PFOS was approximately 2.6-fold higher than that of PFOA.
Perfluorooctanoic acid (PFOA) and perfluorooctanesulfonic acid (PFOS) are synthetic chemicals that have been used in various industries and household products. These can easily accumulate in the human body, causing adverse effects on human health. In this study, a high-performance liquid chromatography-tandem mass spectrometry method was developed and validated for the simultaneous analysis of PFOA and linear PFOS in human serum. Owing to a lack of PFOA- and PFOS-free human serum, 13C8-PFOA and 13C8-PFOS were used as surrogate analytes for quantification. A sensitive and selective sample preparation method was developed and optimized by combining solid-phase extraction and protein precipitation method. The lower limit of quantification was 0.05 ng/mL, and the analytical response was linear up to 10 ng/mL for both PFOA and linear PFOS. Chromatographic separation of the linear PFOS from branched isomers was achieved within 5.5 min. The method was validated at various concentrations and afforded acceptable accuracy and precision values. After validation, the method was successfully applied to evaluate the exposure levels of PFOA and linear PFOS in the Korean population. The serum concentrations of PFOA and linear PFOS were 0.42–28.3 ng/mL and 0.81–57.6 ng/mL, respectively. The median concentration of linear PFOS was approximately 2.6-fold higher than that of PFOA. The concentration of PFOA was higher in women than men (p < 0.05) and that of linear PFOS was not significantly different between men and women. Therefore, a sensitive, selective, and reliable bioanalytical method was developed and validated. This method can potentially be applied to biomonitoring studies involving PFOA and linear PFOS.
The purpose of this study is to develop a solid dispersion system with improved dissolution, absorption, and patient compliance of poorly water-soluble celecoxib (CXB). Instead of sodium lauryl ...sulfate (SLS), an anionic surfactant used in the marketed product (Celebrex
), solubilization was performed using non-ionic surfactants with low toxicity. Cremophor RH40 (Cre-RH) was selected as the optimal solubilizer. Granules and tablets containing CXB and Cre-RH were prepared via fluid-bed and tableting processes, respectively. The morphology, crystallinity, flowability, dissolution, and pharmacokinetics for CXB-solid dispersion granules (SDGs) and the hardness and friability for CXB-solid dispersion tablets (SDTs) were evaluated. The solubility of CXB was found to be increased by about 717-fold when using Cre-RH. The dissolution of granules containing Cre-RH was found to be increased greatly compared with CXB API and Celebrex
(66.9% versus 2.3% and 37.2% at 120 min). The improvement of the dissolution was confirmed to be the same as that of granules in tablets. The CXB formulation resulted in 4.6- and 4.9-fold higher AUC
and
of CXB compared with those of an oral dose of CXB powder in rats. In short, these data suggest that the solid dispersion based on Cre-RH-a non-toxic solubilizer, non-ionic surfactant- may be an effective formulation for CXB to enhance its oral bioavailability and safety.
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