Design of cathepsin-sensitive linkers for tumor-selective bioconjugate drug delivery.

Cysteine cathepsin, particularly cathepsin B, have emerged as pivotal enzymatic targets in the design of drug delivery systems owing to their overexpression in diverse pathological conditions, most notably cancer. This review provides a comprehensive overview of cathepsin B-cleavable linkers, emphasizing their role in current bioconjugate design and their application across multiple therapeutic platforms. It also provides a comparative overview of linker engineering guided by cathepsin B, ranging from simple dipeptides constructs to modified peptide linkers.

Clinical Utility of Salivary Steroid Profiling for the Differential Diagnosis of Adrenal Diseases.

Context: Although salivary steroid sampling offers several advantages, the diagnostic potential of salivary steroid metabolites remains largely unexplored.Objective To evaluate the diagnostic utility of salivary steroid profiling in patients with adrenal diseases.

Design: Prospective multicenter study.

Pulse pressure as a predictor of Alzheimer's disease biomarkers and cognitive decline: The moderating role of APOE ε4.

Background: Elevated pulse pressure (PP), indicative of arterial stiffness, has been implicated in cognitive impairment and Alzheimer's disease (AD) pathology. However, its role in preclinical AD and interactions with genetic risk factors like apolipoprotein E ε4 (APOE4) remain unclear.

Objectives: To investigate the association between baseline PP and AD biomarkers (amyloid-beta (Aβ) and tau) and cognitive decline, and to determine whether APOE4 carrier status moderates these relationships.

Efficacy of pulsed radiofrequency treatment duration to the lumbar dorsal root ganglion in lumbar radicular pain: a double-blind randomized controlled trial.

Background: Pulsed radiofrequency (PRF) of the dorsal root ganglion (DRG) is a minimally invasive treatment for lumbar radicular pain (LRP), but the optimal stimulation duration remains uncertain. Preclinical evidence suggests that extended PRF may enhance neuromodulation, yet comparative clinical data are limited. This randomized, double-blind controlled trial aimed to compare the efficacy according to duration of PRF of DRG in patients with LRP.

The Clinical Impact of Intravascular Imaging-Guided Percutaneous Coronary Intervention in Acute Myocardial Infarction Patients with High Thrombus Burden.

Despite the established clinical efficacy following intravascular imaging (IVI)-guided percutaneous coronary intervention (PCI) than angiography-guided PCI, evidence regarding prognostic benefits of IVI-guided PCI in acute myocardial infarction (AMI) patients with high thrombus burden remains limited. Using the nationwide registries of KAMIR-NIH and KAMIR-V, we evaluated the prognostic impact of IVI-guided PCI in AMI patients with high thrombus burden. A total of 4,074 patients with AMI and TIMI thrombus grades 4 or 5 who underwent aspiration thrombectomy were selected, of whom 892 patients (21.

Efficacy of ophthalmic examinations for predicting vascular calcification in patients undergoing maintenance hemodialysis.

Background: In maintenance hemodialysis (MHD) patients, vascular calcification can be detected not only in coronary vessels but also in ocular areas. However, ophthalmic examinations are not sufficiently validated to measure the degree of vascular calcification.

Methods: This study was performed prospectively, involving 32 MHD patients.

Profiling Cytokines According to the Presence or Absence of Small-for-Gestational Age Using Amniotic Fluid Retrieved During Cesarean Section From Pregnant Women With Early-Onset Preeclampsia.

Background: Preeclampsia (PE) is a hypertensive disorder and a major cause of maternal and fetal mortality. We aimed to investigate the molecular properties of early-onset PE, which requires delivery before 34 weeks' gestation by analyzing the molecular cytokine profile of amniotic fluid obtained during cesarean section from pregnant women with early-onset PE, based on the presence or absence of small-for-gestational age (SGA).

Methods: This study included 73 pregnant women with early-onset PE among which 21 women had SGA infants, whose birth weight was less than the 10th percentile of the gestational age-specific birth weight.

Long-Term Anticoagulation Discontinuation After Catheter Ablation for Atrial Fibrillation: The ALONE-AF Randomized Clinical Trial.

Importance: Data from randomized clinical trials on a long-term anticoagulation strategy for patients after catheter-based ablation for atrial fibrillation (AF) are lacking.

Objective: To evaluate whether discontinuing oral anticoagulant therapy provides superior clinical outcomes compared with continuing oral anticoagulant therapy in patients without documented atrial arrhythmia recurrence after catheter ablation for AF.

Design, Setting, And Participants: A randomized clinical trial including 840 adult patients (aged 19-80 years) who were enrolled and randomized from July 28, 2020, to March 9, 2023, at 18 hospitals in South Korea.

Liposomal drug delivery system for lung diseases: Recent advancement and future perspectives.

Lung diseases such as asthma, chronic respiratory diseases, and lung cancer are among the most prevalent and vulnerable health conditions. Various therapeutic approaches, including nucleic acids, peptides, and small molecules have been developed along with different delivery strategies for their treatment. Liposomes have been recognized as promising delivery candidates attributed to their biocompatibility, biodegradability, and ability to encapsulate both hydrophilic and hydrophobic drugs effectively.

Left Atrial Appendage Characteristics Assessed with Cardiac Computed Tomography in Patients with Atrial Fibrillation and Severe Mitral Valve Disease.

Purpose: The morphological and functional characteristics and clinical significance of the left atrial appendage (LAA) are well established in patients with non-valvular atrial fibrillation (AF). However, data on the LAA characteristics in patients with mitral valve (MV) disease are limited. This study aimed to identify the LAA characteristics in AF patients with severe MV disease.

Novel Neuroactive Steroid Analogs and Voltage-Dependent Blockers of Ca3.2 Currents, B372 and YX23, Are Effective Anti-Nociceptives with Diminished Sedative Properties in Intact Female Mice.

Although opioids are effective in treating pain, they cause serious side effects. The use of regional anesthesia, although effective in the perioperative period, may not be suitable if mobility and lack of numbness is desired. Hence, there is a clear need for novel pain therapies.

Temporal modulation of antiplatelet therapy in high-risk patients undergoing complex percutaneous coronary intervention: the TAILORED-CHIP randomized clinical trial.

Background And Aims: Limited data exist on optimal antiplatelet strategies for high-risk patients undergoing complex percutaneous coronary intervention (PCI). This study aimed to investigate the efficacy and safety of tailored antiplatelet treatment with temporal modulation of the intensity of platelet inhibition in patients undergoing complex high-risk PCI.

Methods: We randomly assigned 2018 patients with high-risk anatomical or clinical characteristics undergoing complex PCI to a tailored antiplatelet strategy with early escalation (low-dose ticagrelor at 60 mg twice daily plus aspirin <6 months) and late de-escalation (clopidogrel monotherapy >6 months) or dual antiplatelet therapy (clopidogrel plus aspirin for 12 months).

Risk, reward and loss in addictive behavior: a six-year cross-lagged panel study.

Decision making in the context of addiction is characterized by altered values regarding risk and reward, but the long-term and reciprocal relationship between value-based decision-making and addictive behavior remains poorly understood. In this study, 338 individuals (19-27 years, 59% female) from a community sample participated in a baseline assessment, including clinical interviews on addictive behaviors (quantity of use, frequency of use, DSM-5 criteria) and a task battery to assess four facets of value-based decision-making (delay aversion, risk-seeking for gains and losses, and loss aversion). Follow-up assessments were conducted after 3 and 6 years, with 75% and 71% of participants retained, respectively.

The impact of heated humidified circuits on arterial oxygenation during one-lung ventilation in thoracic surgery: a randomized controlled trial.

Purpose: One-lung ventilation (OLV) during thoracic surgery often disturbs systemic oxygenation. Hypoxic pulmonary vasoconstriction is influenced by body temperature; however, the effect of heated humidified circuits on hypoxic pulmonary vasoconstriction and arterial oxygenation during OLV remains unclear. This study aimed to investigate the impact of heated humidified circuits on arterial oxygenation during OLV for thoracic surgery, compared with conventional non-heated circuits.

Current Narrative Review-Application of Blood Flow Restriction Exercise in Clinical Knee Problems.

Quadricep weakness is frequently observed in patients following anterior cruciate ligament (ACL) injury or in those with knee osteoarthritis, often contributing to functional impairments and persistent symptoms. While high-intensity resistance training has been shown to effectively improve muscle strength, its application may be limited in certain populations due to pain or the risk of surgical complications. In recent years, blood flow restriction (BFR) training has emerged as a promising alternative.

Stereotactic Ablative Radiotherapy for Delayed Retrobulbar Metastasis of Renal Cell Carcinoma: Therapeutic Outcomes and Practical Insights.

We present a rare case of delayed retrobulbar and adrenal metastases from renal cell carcinoma (RCC), diagnosed 5.5 years after radical nephrectomy. The patient exhibited symptomatic orbital involvement, with imaging revealing a hypervascular retrobulbar mass and an incidental right adrenal lesion, indicative of an oligometastatic state.

Inhibitory Effects of 3-Deoxysappanchalcone on Particulate-Matter-Induced Pulmonary Injury.

Fine particulate matter (PM) exposure has been linked to increased lung damage due to compromised vascular barrier function, while 3-deoxysappanchalcone (3-DSC), a chalcone derived from , is known for its pharmacological benefits such as anti-cancer, anti-inflammatory, and antioxidant effects; however, its potential role in mitigating PM-induced pulmonary damage remains unexplored. To confirm the inhibitory effects of 3-DSC on PM-induced pulmonary injury, this research focused on evaluating how 3-DSC influences PM-induced disruption of the barrier of the endothelial cells (ECs) in the lungs and the resulting pulmonary inflammation. Permeability, leukocyte migration, proinflammatory protein activation, reactive oxygen species (ROS) generation, and histology were assessed in PM-treated ECs and mice.

Clinical Relevance of Fractional Flow Reserve-Guided Percutaneous Coronary Interevention According to Left Ventricular Ejection Fraction in Patients With Acute Myocardial Infarction and Multivessel Disease.

Background: Fractional flow reserve (FFR)-guided or angiography-guided complete revascularization has not been evaluated in patients with acute myocardial infarction (AMI) with multivessel disease and reduced left ventricular ejection fraction (LVEF). This study sought to evaluate the impact of FFR-guided percutaneous coronary intervention (PCI) for patients with AMI with multivessel disease according to left ventricular systolic function.

Methods: We performed a prespecified analysis of the FRAME-AMI (Fractional Flow Reserve Versus Angiography-Guided Strategy in Acute Myocardial Infarction With Multivessel Disease) trial, which randomly allocated 562 patients to undergo either FFR-guided PCI (FFR ≤0.

Influence of urinary creatinine concentration and specific gravity correction in exposure assessment: Comparison between chronic kidney disease patients and general population.

Urine is a favored matrix for biomonitoring of several important classes of chemicals. Because of variations in concentration, however, urine is often adjusted for dilution. Urinary creatinine (Cr) and specific gravity (SG) have been frequently employed for this purpose.

Validation study of spectrophotometric direct peptide reactivity assay (spectro-DPRA), a newly modified in chemico skin sensitization test method.

This study was conducted to evaluate the accuracy and reliability of the Spectro-DPRA, an enhanced method for the OECD TG 442C (direct peptide reactivity assay, DPRA), serving as an alternative to animal testing for skin sensitization. The validation of Spectro-DPRA was executed across four participating laboratories (Lab 1, Lab 2, Lab 3, and Lab 4, the latter only participating in the proficiency test) adhering to GLP principles. It covered transferability, proficiency, within laboratory and between laboratory reproducibility tests, and a predictive capacity test using 40 additional substances.

Exploring the efficacy and safety of dual antiplatelet therapy in patients with embolic stroke of undetermined source according to stroke risk stratification: Propensity-score matched analysis.

Introduction: Dual antiplatelet therapy (DAPT) is widely used for embolic stroke of undetermined source (ESUS) despite limited evidence regarding its efficacy and safety. This study compared DAPT and single antiplatelet therapy (SAPT) in patients with ESUS during hospitalization (first 7 days) and up to 30 days post-stroke, identifying subgroups that benefit most from DAPT.

Methods: We retrospectively analyzed data from 4,505 patients with ESUS enrolled in a multicenter registry from 2014 to 2019.

Preoperative Tyrosine Levels as Predictive Biomarkers for Excessive Fat-Free Mass Loss Following Laparoscopic Sleeve Gastrectomy in Patients with Morbid Obesity.

: Fat-free mass (FFM) loss after metabolic and bariatric surgery (MBS) is associated with adverse long-term outcomes, including osteoporosis. Identifying biomarkers that predict excessive FFM loss can improve perioperative patient management and postoperative risk stratification. This study investigated whether preoperative amino acid metabolite (AAM) levels could predict excessive FFM loss after laparoscopic sleeve gastrectomy (LSG).

Analysis of risk factors for the recurrence of gestational diabetes in subsequent pregnancy: A nationwide population-based study in South Korea.

We compared the obstetric and neonatal outcomes of women with and without gestational diabetes recurrence during subsequent pregnancy and identified the risk factors for gestational diabetes recurrence. In this nationwide population-based study, we analyzed pregnant women and their neonates delivered in Korea between January 2015 and December 2021 using the Korea National Health Insurance claims and National Health-Screening Program for Infants and Children databases. In total, 1985,678 pregnant women were analyzed, of whom 15,086 were diagnosed with gestational diabetes in their first pregnancy.