In light of the burgeoning successes of cancer immunotherapy, glioblastoma (GBM) remains refractory due to an immunosuppressive microenvironment originating from its molecular heterogeneity. Thus, identifying promising therapeutic targets for treating GBM and discovering methodologies to effectively regulate them is still a tremendous challenge. Here we describe photodynamic protein tyrosine phosphatase 1B (PTP1B) proteolysis mediated by a proteolysis-targeting chimera (PROTAC) nanoassembly. The PTP1B-targeting PROTAC is conjugated with a photosensitizer via a cathepsin B (Cat B)-cleavable peptide, which spontaneously forms nanoassemblies due to intermolecular π-π stacking interactions. In GBM models, PROTAC nanoassemblies significantly accumulate in the tumor region across the disrupted blood-brain barrier (BBB), triggering a burst release of the photosensitizer and active PROTAC by Cat B-mediated enzymatic cleavage. Upon laser irradiation, photodynamic therapy (PDT) synergizes with PROTAC-mediated PTP1B proteolysis to induce potent immunogenic cell death (ICD) in tumor cells. Subsequently, persistent PTP1B degradation by nanoassemblies in Cat B-overexpressed intratumoral T cells downregulates exhaustion markers, reinvigorating their functionality. These sequential processes of photodynamic PTP1B proteolysis ultimately augment T cell-mediated antitumor immunity as well as protective immunity, completely eradicating the primary GBM and preventing its recurrence. Overall, our findings underscore the therapeutic potential of combining PDT with PROTAC activity for GBM immunotherapy.

Objectives: Sepsis is a leading global cause of mortality, and predicting its outcomes is vital for improving patient care. This study explored the capabilities of ChatGPT, a state-of-the-art natural language processing model, in predicting in-hospital mortality for sepsis patients. Methods: This study utilized data from the Korean Sepsis Alliance (KSA) database, collected between 2019 and 2021, focusing on adult intensive care unit (ICU) patients and aiming to determine whether ChatGPT could predict all-cause mortality after ICU admission at 7 and 30 days. Structured prompts enabled ChatGPT to engage in in-context learning, with the number of patient examples varying from zero to six. The predictive capabilities of ChatGPT-3.5-turbo and ChatGPT-4 were then compared against a gradient boosting model (GBM) using various performance metrics. Results: From the KSA database, 4,786 patients formed the 7-day mortality prediction dataset, of whom 718 died, and 4,025 patients formed the 30-day dataset, with 1,368 deaths. Age and clinical markers (e.g., Sequential Organ Failure Assessment score and lactic acid levels) showed significant differences between survivors and non-survivors in both datasets. For 7-day mortality predictions, the area under the receiver operating characteristic curve (AUROC) was 0.70–0.83 for GPT-4, 0.51–0.70 for GPT-3.5, and 0.79 for GBM. The AUROC for 30-day mortality was 0.51–0.59 for GPT-4, 0.47–0.57 for GPT-3.5, and 0.76 for GBM. Zero-shot predictions using GPT-4 for mortality from ICU admission to day 30 showed AUROCs from the mid-0.60s to 0.75 for GPT-4 and mainly from 0.47 to 0.63 for GPT-3.5. Conclusions GPT-4 demonstrated potential in predicting short-term in-hospital mortality, although its performance varied across different evaluation metrics.

Evaluating cell metabolism is crucial during pluripotent stem cell (PSC) differentiation and somatic cell reprogramming as it affects cell fate. As cultured stem cells are heterogeneous, a comparative analysis of relative metabolism using existing metabolic analysis methods is difficult, resulting in inaccuracies. In this study, we measured human PSC basal metabolic levels using a Seahorse analyzer. We used fibroblasts, human induced PSCs, and human embryonic stem cells to monitor changes in basal metabolic levels according to cell number and determine the number of cells suitable for analysis. We evaluated normalization methods using glucose and selected the most suitable for the metabolic analysis of heterogeneous PSCs during the reprogramming stage. The response of fibroblasts to glucose increased with starvation time, with oxygen consumption rate and extracellular acidification rate responding most effectively to glucose 4 hours after starvation and declining after 5 hours of starvation. Fibroblasts and PSCs achieved appropriate responses to glucose without damaging their metabolism 2∼4 and 2∼3 hours after starvation, respectively. We developed a novel method for comparing basal metabolic rates of fibroblasts and PSCs, focusing on quantitative analysis of glycolysis and oxidative phosphorylation using glucose without enzyme inhibitors. This protocol enables efficient comparison of energy metabolism among cell types, including undifferentiated PSCs, differentiated cells, and cells undergoing cellular reprogramming, and addresses critical issues, such as differences in basal metabolic levels and sensitivity to normalization, providing valuable insights into cellular energetics.

In May 2023, the Committee of Clinical Practice Guidelines of the Korean Diabetes Association published the revised clinical practice guidelines for Korean adults with diabetes and prediabetes. We incorporated the latest clinical research findings through a comprehensive systematic literature review and applied them in a manner suitable for the Korean population. These guidelines are designed for all healthcare providers nationwide, including physicians, diabetes experts, and certified diabetes educators who manage patients with diabetes or individuals at risk of developing diabetes. Based on recent changes in international guidelines and the results of a Korean epidemiological study, the recommended age for diabetes screening has been lowered. In collaboration with the relevant Korean medical societies, recently revised guidelines for managing hypertension and dyslipidemia in patients with diabetes have been incorporated into this guideline. An abridgment containing practical information on patient education and systematic management in the clinic was published separately.

Purpose: Mycoplasma pneumoniae pneumonia (MP) is a major cause of community-acquired pneumonia (CAP) in children and is associated with extrapulmonary manifestations (EPM). The incidence and risk factors for EPM in children are unknown. Methods: This was a retrospective study involving 65,243 pediatric patients with CAP between 2010 and 2015 at 23 nationwide hospitals in South Korea. Medical records were reviewed to collect information regarding the clinical characteristics, radiological results, and laboratory findings. Logistic regression with multivariate analysis was performed to evaluate the risk factors associated with EPM in MP. Results: The incidence of EPM was 23.9%, including elevation of liver enzymes (18.1%), mucocutaneous manifestations (4.4%), proteinuria (4.1%), cardiovascular and neurological manifestations (0.4%), hematologic manifestations (0.2%), and arthritis (0.2%). Statistical analysis showed that mucocutaneous manifestations significantly increased with elevated alanine aminotransferase (adjusted odds ratio [aOR], 3.623; 95% confidence interval [CI], 1.933-6.790) and atopic sensitization (aOR, 2.973; 95% CI, 1.615–5.475) and decreased with respiratory virus coinfection (aOR, 0.273; 95% CI, 0.084–0.887). Elevated liver enzymes were significantly associated with elevated lactate dehydrogenase (aOR, 3.055; 95% CI, 2.257–4.137), presence of pleural effusion (aOR, 2.635; 95% CI, 1.767–3.930), and proteinuria with respiratory virus coinfection (aOR, 2.245; 95% CI, 1.113–4.527). Conclusion Approximately 24% of pediatric patients with MP had various EPM. As the risk factors associated with each EPM were different, it is necessary to evaluate the various clinical aspects and findings of MP to predict and prepare for the occurrence of EPM.

Background: Subclinical left ventricular diastolic dysfunction (LVDD) is an emerging consequence of increased insulin resistance, and dyslipidemia is one of the few correctable risk factors of LVDD. This study evaluated the role of mean and visit-to-visit variability of lipid measurements in risk of LVDD in a healthy population. Methods: This was a 3.7-year (interquartile range, 2.1 to 4.9) longitudinal cohort study including 2,817 adults (median age 55 years) with left ventricular ejection fraction >50% who underwent an annual or biannual health screening between January 2008 and July 2016. The mean, standard deviation (SD), coefficient of variation (CV), variability independent of the mean (VIM), and average real variability of total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), apolipoprotein B (apoB), non-HDL-C, and triglycerides were obtained from three to six measurements during the 5 years preceding the first echocardiogram. Results: Among the 2,817 patients, 560 (19.9%) developed LVDD. The mean of no component of lipid measurements was associated with risk of LVDD. CV (hazard ratio [HR], 1.35; 95% confidence interval [CI], 1.10 to 1.67), SD (HR, 1.27; 95% CI, 1.03 to 1.57), and VIM (HR, 1.26; 95% CI, 1.03 to 1.55) of LDL-C and all the variability parameters of apoB were significantly associated with development of LVDD. The association between CV-LDL and risk of LVDD did not have significant interaction with sex, increasing/decreasing trend at baseline, or use of stain and/or lipid-modifying agents. Conclusion The variability of LDL-C and apoB, rather than their mean, was associated with risk for LVDD.

The Committee of Clinical Practice Guidelines of the Korean Diabetes Association (KDA) updated the previous clinical practice guidelines for Korean adults with diabetes and prediabetes and published the seventh edition in May 2021. We performed a comprehensive systematic review of recent clinical trials and evidence that could be applicable in real-world practice and suitable for the Korean population. The guideline is provided for all healthcare providers including physicians, diabetes experts, and certified diabetes educators across the country who manage patients with diabetes or the individuals at the risk of developing diabetes mellitus. The recommendations for screening diabetes and glucose-lowering agents have been revised and updated. New sections for continuous glucose monitoring, insulin pump use, and non-alcoholic fatty liver disease in patients with diabetes mellitus have been added. The KDA recommends active vaccination for coronavirus disease 2019 in patients with diabetes during the pandemic. An abridgement that contains practical information for patient education and systematic management in the clinic was published separately.

Background: Cardiovascular autonomic neuropathy (CAN) is a common microvascular complication of diabetes and related to albuminuria in diabetic nephropathy (DN). Urinary N-acetyl-β-D-glucosaminidase (uNAG) is a renal tubular injury marker which has been reported as an early marker of DN even in patients with normoalbuminuria. This study evaluated whether uNAG is associated with the presence and severity of CAN in patients with type 1 diabetes mellitus (T1DM) without nephropathy. Methods: This cross-sectional study comprised 247 subjects with T1DM without chronic kidney disease and albuminuria who had results for both uNAG and autonomic function tests within 3 months. The presence of CAN was assessed by age-dependent reference values for four autonomic function tests. Total CAN score was assessed as the sum of the partial points of five cardiovascular reflex tests and was used to estimatethe severity of CAN. The correlations between uNAG and heart rate variability (HRV) parameters were analyzed. Results: The association between log-uNAG and presence of CAN was significant in a multivariate logistic regression model (adjusted odds ratio, 2.39; 95% confidence interval [CI], 1.08 to 5.28; P=0.031). Total CAN score was positively associated with loguNAG (β=0.261, P=0.026) in the multivariate linear regression model. Log-uNAG was inversely correlated with frequency-domain and time-domain indices of HRV. Conclusion This study verified the association of uNAG with presence and severity of CAN and changes in HRV in T1DM patients without nephropathy. The potential role of uNAG should be further assessed for high-risk patients for CAN in T1DM patients without nephropathy.

Although isolated contralateral tongue deviation following unilateral cortical infarction was occasionally reported, the unilateral lesion usually produces no significant deficit of tongue motility considering bilateral supranuclear innervation of the hypoglossal nerve. We observed a patient with obvious tongue paralysis, including intrinsic muscles, caused by ischemic stroke involving the motor area of the tongue in the primary motor cortex.