Connective tissue disease (CTD), comprising a range of autoimmune disorders, is often accompanied by lung involvement, which can lead to life-threatening complications. The primary types of CTDs that manifest as interstitial lung disease (ILD) include rheumatoid arthritis, systemic sclerosis, Sjögren’s syndrome, mixed CTD, idiopathic inflammatory myopathies, and systemic lupus erythematosus. CTD-ILD presents a significant challenge in clinical diagnosis and management due to its heterogeneous nature and variable prognosis. Early diagnosis through clinical, serological, and radiographic assessments is crucial for distinguishing CTD-ILD from idiopathic forms and for implementing appropriate therapeutic strategies. Hence, we have reviewed the multiple clinical manifestations and diagnostic approaches for each type of CTD-ILD, acknowledging the diversity and complexity of the disease. The importance of a multidisciplinary approach in optimizing the management of CTD-ILD is emphasized by recent therapeutic advancements, which include immunosuppressive agents, antifibrotic therapies, and newer biological agents targeting specific pathways involved in the pathogenesis. Therapeutic strategies should be customized according to the type of CTD, the extent of lung involvement, and the presence of extrapulmonary manifestations. Additionally, we aimed to provide clinical guidance, including therapeutic recommendations, for the effective management of CTD-ILD, based on patient, intervention, comparison, outcome (PICO) analysis.

Purpose: Chronic pelvic pain syndrome (CPPS) is a multifactorial condition that can significantly diminish quality of life. Although some patients have reported persistent pelvic pain after radical prostatectomy (RP), the prevalence and direct causal relationship between CPPS and RP remain unclear. This multicenter prospective study aimed to evaluate the efficacy of Urovaxom for improving CPPS symptoms. Materials and Methods: A total of 52 prostate cancer patients who underwent RP were enrolled and administered Urovaxom (60 mg/day) for 12 weeks. Changes in National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI), overactive bladder symptom score (OABSS), International Prostate Symptom Score (IPSS), and inflammation markers (white blood cell [WBC], C-reactive protein [CRP]) were analyzed using the Wilcoxon signed-rank test. Results: After 12 weeks of treatment, the NIH-CPSI total score significantly decreased from 19 (interquartile range [IQR], 16–23) to 12.5 (IQR, 8.0–16.8) (p<0.001). The OABSS total score decreased from 8 (IQR, 4–11) to 5 (IQR, 3.0–7.8), and the IPSS total score decreased from 13.5 (IQR, 10.0–22.8) to 10.5 (IQR, 5.0–17.0) (p<0.001). WBC levels showed a slight increase (p=0.028), but the clinical relevance of this change is uncertain and warrants further investigation. CRP changes were not statistically significant (p=0.274). Conclusions Urovaxom demonstrated significant efficacy in improving CPPS symptoms, particularly pain and reduced quality of life, in patients following RP. These findings suggest Urovaxom as a potential therapeutic option for CPPS after management using RP.

Background: s/Aims: In hepatocellular carcinoma (HCC), which exhibits high mortality and recurrence rates globally, the traits of cancer stem cells (CSCs) that significantly influence recurrence and metastasis are not well understood. CSCs are self-renewing cell types identified in most liquid and solid cancers, contributing to tumor initiation, growth, resistance, recurrence, and metastasis following chemo-radiotherapy or trans-arterial chemoembolization therapy. Methods: CSCs are classified based on the expression of cell surface markers such as CD133, which varies depending on the tumor type. Proteomic analysis of liver cancer cell lines with cancer stem cell potential and HCC cancer cell lines lacking stem cell propensity was conducted to compare and analyze specific expression patterns. Results: Proteomic profiling and enrichment analysis revealed higher expression of the calcium-binding protein S100 family in CD133+ Huh7 cells than in CD133- or wild-type cells. Furthermore, elevated expression of S100 family members was confirmed in an actual CD133+ liver cancer cell line via protein-protein network analysis and quantitative polymerase chain reaction (qPCR). Conclusion The S100 family members are not only new markers of cancer stem cells but will also assist in identifying new treatment strategies for CSC metastasis and tumor advancement.

Background: Cardiovascular diseases are the leading cause of mortality after liver transplantation (LT). Although the impact of secondary tricuspid regurgitation (TR) with severe pulmonary hypertension (PH) is well investigated, the impact of primary TR with tricuspid valve incompetence (TVI) on LT outcomes remains unclear. We aimed to investigate the prevalence and impact of primary TR with TVI on LT outcomes in a large-volume LT center. Methods: We retrospectively examined 5 512 consecutive LT recipients who underwent routine pretransplant echocardiography between 2008 and 2020. Patients were categorized based on the presence of anatomical TVI, specifically defined by incomplete coaptation, coaptation failure, prolapse, and flail leaflets of tricuspid valve (TV). Propensity score (PS)-based inverse probability weighting (IPW) was used to balance clinical and cardiovascular risk variables. The outcomes were one-year cumulative all-cause mortality and 30-day major adverse cardiovascular events (MACE). Results: Anatomical TVI was identified in 14 patients (0.3%). Although rare, these patients exhibited significantly lower post-LT one-year survival rates (64.3% vs. 91.5%, P < 0.001) and higher 30-day MACE rates (42.9% vs. 16.9%, P = 0.026) than patients without TVI. They also had worse survival irrespective of echocardiographic evidence of PH (P < 0.001) and exhibited higher one-year mortality (IPW-adjusted hazard ratio: 4.09, P = 0.002) and increased 30-day MACE rates (IPW-adjusted odds ratio: 1.24, P = 0.048). Conclusions Primary TR with anatomical TVI was associated with significantly reduced one-year survival and increased post-LT MACE rates. These patients should be prioritized similarly to those with secondary TR with severe PH, with appropriate pretransplant evaluations and treatments to improve survival outcomes.

Alzheimer disease (AD) diagnosis is confirmed using a medley of modalities, such as the detection of amyloid-β (Aβ) neuritic plaques and neurofibrillary tangles with positron electron tomography (PET) or the appraisal of irregularities in cognitive function with examinations. Although these methods have been efficient in confirming AD pathology, the rising demand for earlier intervention during pathogenesis has led researchers to explore the diagnostic potential of fluid biomarkers in cerebrospinal fluid (CSF) and plasma. Since CSF sample collection is invasive and limited in quantity, biomarker detection in plasma has become more attractive and modern advancements in technology has permitted more efficient and accurate analysis of plasma biomolecules. In this study, we found that a composite of standard factors, Aβ40 and total tau levels in plasma, divided by the variation factor, plasma Aβ42 level, provide better correlation with amyloid neuroimaging and neuropsychological test results than a level comparison between total tau and Aβ42 in plasma. We collected EDTA-treated blood plasma samples of 53 subjects, of randomly selected 27 AD patients and 26 normal cognition (NC) individuals, who received amyloid-PET scans for plaque quantification, and measured plasma levels of Aβ40, Aβ42, and total tau with digital enzyme-linked immunosorbent assay (ELISA) in a blinded manner. There was difficulty distinguishing AD patients from controls when analyzing biomarkers independently. However, significant differentiation was observed between the two groups when comparing individual ratios of total-tau×Aβ40/Aβ42. Our results indicate that collectively comparing fluctuations of these fluid biomarkers could aid in monitoring AD pathogenesis.

Triple-negative breast cancer (TNBC) is an aggressive cancer subtype lacking targeted therapies and is characterized by highrecurrence rates and poor prognosis. Recent advances in targeting DNA damage response (DDR) pathways using poly (ADP‒ri-bose) polymerase (PARP) inhibitors offer promising therapeutic strategies, especially for TNBC patients with BRCA1/2 mutations.This study reports the development and characterization of ART-446, a novel and selective CHK2 inhibitor. ART-446 showed potent activity against TNBC, regardless of BRCA deficiency, and it also reversed PARP inhibitor resistance. ART-446 potentlyinhibited CHK2 (IC50 : 9.06 nM) with high selectivity over other kinases; it synergized with the PARP inhibitor olaparib, enhancingDNA damage, inducing G2/M cell cycle arrest, and promoting apoptosis in both BRCA-mutant and wild-type TNBC cells. Mechanistic analyses revealed that ART-446 sensitized BRCA mutant and WT cells to PARP inhibitors by impairing DNA repair and increasing the accumulation of DNA damage. Importantly, ART-446 disrupted both homologous recombination and nonhomologous end-joining repair pathways, addressing a key limitation of PARP inhibitor monotherapy—resistance in BRCA-proficient cancers.In vivo, the combination of ART-446 and olaparib significantly reduced tumor growth in TNBC xenograft models without noticeable toxicity. The combined treatment increased DNA damage signaling, as evidenced by elevated γH2AX levels, and enhanced the sensitivity of BRCA2-deficient cells to ART-446. These findings underscore the potential of ART-446 to exploit DNA repair deficiencies and overcome resistance mechanisms associated with PARP inhibitors. By addressing the limitations of current treatments and expanding the utility of PARP inhibitors, ART-446 represents a promising candidate for DDR-targeted therapies, offering a novel approach to improve the outcomes of patients with TNBC.

Connective tissue disease (CTD), comprising a range of autoimmune disorders, is often accompanied by lung involvement, which can lead to life-threatening complications. The primary types of CTDs that manifest as interstitial lung disease (ILD) include rheumatoid arthritis, systemic sclerosis, Sjögren’s syndrome, mixed CTD, idiopathic inflammatory myopathies, and systemic lupus erythematosus. CTD-ILD presents a significant challenge in clinical diagnosis and management due to its heterogeneous nature and variable prognosis. Early diagnosis through clinical, serological, and radiographic assessments is crucial for distinguishing CTD-ILD from idiopathic forms and for implementing appropriate therapeutic strategies. Hence, we have reviewed the multiple clinical manifestations and diagnostic approaches for each type of CTD-ILD, acknowledging the diversity and complexity of the disease. The importance of a multidisciplinary approach in optimizing the management of CTD-ILD is emphasized by recent therapeutic advancements, which include immunosuppressive agents, antifibrotic therapies, and newer biological agents targeting specific pathways involved in the pathogenesis. Therapeutic strategies should be customized according to the type of CTD, the extent of lung involvement, and the presence of extrapulmonary manifestations. Additionally, we aimed to provide clinical guidance, including therapeutic recommendations, for the effective management of CTD-ILD, based on patient, intervention, comparison, outcome (PICO) analysis.

Purpose: Chronic pelvic pain syndrome (CPPS) is a multifactorial condition that can significantly diminish quality of life. Although some patients have reported persistent pelvic pain after radical prostatectomy (RP), the prevalence and direct causal relationship between CPPS and RP remain unclear. This multicenter prospective study aimed to evaluate the efficacy of Urovaxom for improving CPPS symptoms. Materials and Methods: A total of 52 prostate cancer patients who underwent RP were enrolled and administered Urovaxom (60 mg/day) for 12 weeks. Changes in National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI), overactive bladder symptom score (OABSS), International Prostate Symptom Score (IPSS), and inflammation markers (white blood cell [WBC], C-reactive protein [CRP]) were analyzed using the Wilcoxon signed-rank test. Results: After 12 weeks of treatment, the NIH-CPSI total score significantly decreased from 19 (interquartile range [IQR], 16–23) to 12.5 (IQR, 8.0–16.8) (p<0.001). The OABSS total score decreased from 8 (IQR, 4–11) to 5 (IQR, 3.0–7.8), and the IPSS total score decreased from 13.5 (IQR, 10.0–22.8) to 10.5 (IQR, 5.0–17.0) (p<0.001). WBC levels showed a slight increase (p=0.028), but the clinical relevance of this change is uncertain and warrants further investigation. CRP changes were not statistically significant (p=0.274). Conclusions Urovaxom demonstrated significant efficacy in improving CPPS symptoms, particularly pain and reduced quality of life, in patients following RP. These findings suggest Urovaxom as a potential therapeutic option for CPPS after management using RP.

Connective tissue disease (CTD), comprising a range of autoimmune disorders, is often accompanied by lung involvement, which can lead to life-threatening complications. The primary types of CTDs that manifest as interstitial lung disease (ILD) include rheumatoid arthritis, systemic sclerosis, Sjögren’s syndrome, mixed CTD, idiopathic inflammatory myopathies, and systemic lupus erythematosus. CTD-ILD presents a significant challenge in clinical diagnosis and management due to its heterogeneous nature and variable prognosis. Early diagnosis through clinical, serological, and radiographic assessments is crucial for distinguishing CTD-ILD from idiopathic forms and for implementing appropriate therapeutic strategies. Hence, we have reviewed the multiple clinical manifestations and diagnostic approaches for each type of CTD-ILD, acknowledging the diversity and complexity of the disease. The importance of a multidisciplinary approach in optimizing the management of CTD-ILD is emphasized by recent therapeutic advancements, which include immunosuppressive agents, antifibrotic therapies, and newer biological agents targeting specific pathways involved in the pathogenesis. Therapeutic strategies should be customized according to the type of CTD, the extent of lung involvement, and the presence of extrapulmonary manifestations. Additionally, we aimed to provide clinical guidance, including therapeutic recommendations, for the effective management of CTD-ILD, based on patient, intervention, comparison, outcome (PICO) analysis.