Association of Cough Severity with Asthma Control and Quality of Life in Patients with Severe Asthma.

PURPOSE: Symptoms are important components in determining asthma control and in the adjustment of treatment levels. However, clinical relevance of cough in severe asthma is not well-understood. This study aimed to evaluate the severity and association of cough with patient-reported outcomes (PROs) in patients with severe asthma. METHODS: This study analyzed cross-sectional data from the Korean Severe Asthma Registry. The severity of coughing and wheezing symptoms was assessed using a Visual Analog Scale (VAS) ranging from 0 to 100 for each symptom. Additionally, PROs included the Asthma Control Test (ACT), the Severe Asthma Questionnaire (SAQ), and the EuroQoL 5-Dimension (EQ-5D) index. Multivariate linear regression analysis was employed to explore the relationship between cough severity and other PRO scores. RESULTS: A total of 498 patients with severe asthma (age: 57.9 ± 13.1 years, females: 60.2%) were analyzed. The cough VAS score was higher than the wheeze score (median 30, [interquartile range 10-50] vs. 20 [0-50]; P < 0.001). Additionally, 22.5% of patients ranked in a higher tertile for cough severity compared to wheezing, while 18.5% ranked higher for wheezing severity than cough. Significant correlations were observed between cough and wheeze VAS scores (r = 0.61, P < 0.05) and between each symptom's VAS score and the SAQ (cough: r = -0.41, P < 0.001; wheeze: r = -0.52, P < 0.001), ACT scores (cough: r = -0.50, P < 0.001; wheeze: r = -0.63, P < 0.001) and EQ-5D index (cough: r = -0.40, P < 0.001; wheeze: r = -0.45, P < 0.001). In univariate regression analysis, the cough VAS score had weaker descriptive power (R2) values than the wheeze VAS score in relation to the PRO measures. Nevertheless, cough severity remained significantly associated with ACT, SAQ scores and EQ-5D index in multivariate analyses adjusted for wheeze severity and other confounders. CONCLUSION: Cough frequently presents as a severe symptom in patients with severe asthma and could have distinct impact on asthma control and quality of life.

Comparison of partial and total cystectomy for colorectal cancer with histologically confirmed bladder invasion.

BACKGROUND: Although organs are preserved and quality of life is improved, insufficient evidence is available for the oncologic safety of partial cystectomy in patients with colorectal cancer with suspected bladder invasion. Therefore, we aimed to compare partial and total cystectomy outcomes in patients with pathologically confirmed or clinically suspected bladder invasion. METHODS: Patients with colorectal cancer with suspected bladder invasion who underwent R0 resection from 2000 to 2020 were evaluated. Long-term outcomes were determined in patients with histologically confirmed bladder invasion. RESULTS: Of the 151 consecutive patients, 96 (64.6%) had histologically confirmed bladder involvement, and 105 (69.5%) underwent partial cystectomy. Operative time, estimated blood loss, and reoperation rate in ≤30 days were significantly worse in the total cystectomy group than in the partial cystectomy group. The overall recurrence rate was significantly higher in the total cystectomy group than in the partial cystectomy group (39.1% vs 21.9%; P = .046). Five-year overall survival (75.8% vs 53.2%; P = .006) rates were higher in the partial cystectomy group than in the total cystectomy group; however, disease-free survival (60.8% vs 41.6%; P = .088) rates were similar in patients with suspected bladder invasion. In patients with histologically confirmed bladder invasion, 5-year overall survival rates (78.1% vs 52.1%; P = .017) were higher in the partial cystectomy group than in the total cystectomy group; however, disease-free survival rates (53.4% vs 41.2%; P = .220) did not differ significantly. CONCLUSION: R0 resection is associated with favorable long-term outcomes in patients with locally advanced colorectal cancer. If R0 resection is possible, partial cystectomy is considered safe.

Comparative analysis of different surgical approaches for recurrent inguinal hernia: a single-center observational study.

Purpose: Managing recurrent inguinal hernias is complex, and choosing the right surgical approach (laparoscopic vs. open) is vital for patient outcomes. This study compared the outcomes of using the same vs. different surgical approaches for initial and subsequent hernia repairs. Methods: We retrospectively analyzed patients who underwent recurrent inguinal hernia repair at Seoul National University Bundang Hospital between January 2014 and May 2023. Patients were divided into the "concordant" and "discordant" groups, comprising patients who underwent same and different approaches in both surgeries, respectively. Preoperative baseline characteristics, index surgery data, postoperative outcomes, and recurrence rates were analyzed and compared. Results: In total, 131 patients were enrolled; the concordant and discordant groups comprised 31 (open, n = 19; laparoscopic, n = 12) and 100 patients (open to laparoscopic, n = 68; laparoscopic to open, n = 32), respectively. No significant differences were observed in the mean operation time (50.5 ± 21.7 minutes vs. 50.2 ± 20.0 minutes, P = 0.979), complication rates (6.5% vs. 14.0%, P = 0.356), or 36-month cumulative recurrence rates (9.8% vs. 9.8%; P = 0.865). The mean postoperative hospital stay was significantly shorter in the discordant than in the concordant group (1.8 ± 0.7 vs. 1.4 ± 0.6, P = 0.003). Conclusion: Most recurrent inguinal hernia repairs were performed using the discordant surgical approach. Overall, concordance in the surgical approach did not significantly affect postoperative outcomes. Therefore, the selection of the surgical approach based on the patient's condition and surgeon's preference may be advisable.

Highly Permeable Mixed Matrix Membranes for Gas Separation via Dual Defect-Engineered Zeolitic Imidazolate Framework-8.

Defect engineering of metal-organic frameworks (MOFs) is a promising strategy for tailoring the interfacial characteristics between MOFs and polymers, aiming to create high-performance mixed matrix membranes (MMMs). This study introduces a new approach using dual defective alkylamine (AA)-modulated zeolitic imidazolate framework-8 (DAZIF-8), to develop high-flux MMMs. Tributylamine (TBA) and triethylamine (TEA) monodentate ligands coordinate with zinc ions in varying compositions. A mixture of Zn(CH3COO)2·2H2O:2-methylimidazole (Mim):AA in a 1:1.75:5 molar ratio facilitates high-yield coordination between Zn and multiple organic ligands, including Zn-Mim, Zn-TEA, and Zn-TBA (>80%). Remarkably, DAZIF-8 containing 3 mol% TBA and 2 mol% TEA exhibits exceptional characteristics, such as a Brunauer-Emmett-Teller surface area of 1745 m2 g-1 and enhanced framework rigidity. Furthermore, dual Zn-AA coordination sites on the framework's outer surface enhance compatibility with the polyimide (PI) matrix through electron donor-acceptor interactions, enabling the fabrication of high-loading MMMs with excellent mechanical durability. Importantly, the PI/DAZIF-8 (60/40 w/w) MMM demonstrates an unprecedented 759% enhancement in ethylene (C2H4) permeability (281 Barrer) with a moderate ethylene/ethane (C2H4/C2H6) selectivity of 2.95 compared to the PI, surpassing the polymeric upper limit for C2H4/C2H6 separation.

Predictors associated with the rate of progression of nigrostriatal degeneration in Parkinson's disease.

BACKGROUND: Parkinson's disease (PD) manifests as a wide variety of clinical phenotypes and its progression varies greatly. However, the factors associated with different disease progression remain largely unknown. METHODS: In this retrospective cohort study, we enrolled 113 patients who underwent 18F-FP-CIT PET scan twice. Given the negative exponential progression pattern of dopamine loss in PD, we applied the natural logarithm to the specific binding ratio (SBR) of two consecutive 18F-FP-CIT PET scans and conducted linear mixed model to calculate individual slope to define the progression rate of nigrostriatal degeneration. We investigated the clinical and dopamine transporter (DAT) availability patterns associated with the progression rate of dopamine depletion in each striatal sub-region. RESULTS: More symmetric parkinsonism, the presence of dyslipidemia, lower K-MMSE total score, and lower anteroposterior gradient of the mean putaminal SBR were associated with faster progression rate of dopamine depletion in the caudate nucleus. More symmetric parkinsonism and lower anteroposterior gradient of the mean putaminal SBR were associated with faster depletion of dopamine in the anterior putamen. Older age at onset, more symmetric parkinsonism, the presence of dyslipidemia, and lower anteroposterior gradient of the mean putaminal SBR were associated with faster progression rate of dopamine depletion in the posterior putamen. Lower striatal mean SBR predicted the development of LID, while lower mean SBR in the caudate nuclei predicted the development of dementia. DISCUSSION: Our results suggest that the evaluation of baseline clinical features and patterns of DAT availability can predict the progression of PD and its prognosis.

Are sporadic colorectal cancers in young patients distinct from those in elderly patients?

AIM: The aim of this study was to compare the clinicopathological and oncological characteristics of sporadic colorectal cancer (CRC) between young and elderly patients without any genetic mutations that cause hereditary CRC. METHOD: In this cross-sectional, retrospective study conducted at three tertiary referral hospitals, we enrolled 1599 patients with CRC who underwent surgery between January 2010 and December 2017, including 157 young patients (age ≤ 40 years; yCRC) and 1442 elderly patients (age ≥ 70 years; eCRC). The clinicopathological and oncological outcomes were compared between the two groups. RESULTS: The median age at diagnosis was 37 years in the yCRC group (range 33.0-39.2 years) and 76 years in the eCRC group (range 72.0-79.0 years). The yCRC group did not present with advanced stages at diagnosis compared with the eCRC group, and the distribution of tumour stages was similar between the two groups. Microsatellite instability (MSI) testing revealed no difference in the frequency of tumours with high MSI (7.8% in yCRC, 5.8% in eCRC), and the frequency of mutations in the KRAS, NRAS and BRAF genes was also similar. The 3-year overall survival was better in the yCRC group than in the eCRC group (97.4% vs. 83.5%, p < 0.001); however, no such difference was observed in cancer-specific survival. CONCLUSION: Genetically proven sporadic CRCs did not differ significantly between young and elderly patients in terms of tumour stage, tumour location and various molecular features. CLINICAL TRIAL REGISTRATION NUMBER: The study was retrospectively registered with Clinical Trials.gov (no. NCT05601609).

Deep learning model for differentiating nasal cavity masses based on nasal endoscopy images.

BACKGROUND: Nasal polyps and inverted papillomas often look similar. Clinically, it is difficult to distinguish the masses by endoscopic examination. Therefore, in this study, we aimed to develop a deep learning algorithm for computer-aided diagnosis of nasal endoscopic images, which may provide a more accurate clinical diagnosis before pathologic confirmation of the nasal masses. METHODS: By performing deep learning of nasal endoscope images, we evaluated our computer-aided diagnosis system's assessment ability for nasal polyps and inverted papilloma and the feasibility of their clinical application. We used curriculum learning pre-trained with patches of nasal endoscopic images and full-sized images. The proposed model's performance for classifying nasal polyps, inverted papilloma, and normal tissue was analyzed using five-fold cross-validation. RESULTS: The normal scores for our best-performing network were 0.9520 for recall, 0.7900 for precision, 0.8648 for F1-score, 0.97 for the area under the curve, and 0.8273 for accuracy. For nasal polyps, the best performance was 0.8162, 0.8496, 0.8409, 0.89, and 0.8273, respectively, for recall, precision, F1-score, area under the curve, and accuracy. Finally, for inverted papilloma, the best performance was obtained for recall, precision, F1-score, area under the curve, and accuracy values of 0.5172, 0.8125, 0.6122, 0.83, and 0.8273, respectively. CONCLUSION: Although there were some misclassifications, the results of gradient-weighted class activation mapping were generally consistent with the areas under the curve determined by otolaryngologists. These results suggest that the convolutional neural network is highly reliable in resolving lesion locations in nasal endoscopic images.

Cough Response to High-Dose Inhaled Corticosteroids in Patients with Chronic Cough and Fractional Exhaled Nitric Oxide Levels ≥ 25 ppb: A Prospective Study.

This study aimed to investigate the effects of high-dose inhaled corticosteroids (ICS) on chronic cough patients with elevated fractional exhaled nitric oxide (FeNO) levels. In a prospective study, adults with chronic cough and FeNO ≥ 25 ppb, without any other apparent etiology, received fluticasone furoate (200 mcg) for three weeks. Outcomes were evaluated using FeNO levels, cough severity, and Leicester Cough Questionnaire (LCQ) before and after treatment. Of the fifty participants (average age: 58.4 years; 58% female), the treatment responder rate (≥ 1.3-point increase in LCQ) was 68%, with a significant improvement in cough and LCQ scores and FeNO levels post-treatment. However, improvements in cough did not significantly correlate with changes in FeNO levels. These findings support the guideline recommendations for a short-term ICS trial in adults with chronic cough and elevated FeNO levels, but the lack of correlations between FeNO levels and cough raises questions about their direct mechanistic link.

Surface engineered recombinant Escherichia coli for the potential application of the cobalt contaminated wastewater treatment and the photocatalytic dye degradation.

The novel recombinant Escherichia coli strain was construct through cell surface display for the treatment of cobalt contaminated wastewater and dye contaminated wastewater. First, structural analysis of known cobalt binding peptide was conducted and core binding sites were figured out which showing better cobalt binding ability. The cobalt peptides were attached to OmpC to construct cobalt adsorbing recombinant Escherichia coli. The recombinant strain efficiently absorbed and retrieved cobalt from cobalt wastewater by adsorbing 1895 µmol/g DCW of cobalt. Following adsorption, cobalt nanoparticles were synthesized through thermal decomposition of cobalt adsorbed recombinant strain at 500˚C. The nanoparticles exhibited noteworthy photocatalytic properties, demonstrating a substantial capacity for degrading dyes when used as a catalyst at a concentration of 10 mg/dl. These results presenting potential solutions for effective and environmentally friendly approaches to address cobalt and dye contaminated wastewater treatment process.

Preoperative smoking and robot-assisted radical cystectomy outcomes & complications in multicenter KORARC database.

To investigate the influence of preoperative smoking history on the survival outcomes and complications in a cohort from a large multicenter database. Many patients who undergo radical cystectomy (RC) have a history of smoking; however, the direct association between preoperative smoking history and survival outcomes and complications in patients with muscle-invasive bladder cancer (MIBC) who undergo robot-assisted radical cystectomy (RARC) remains unexplored. We conducted a retrospective analysis using data from 749 patients in the Korean Robot-Assisted Radical Cystectomy Study Group (KORARC) database, with an average follow-up duration of 30.8 months. The cohort was divided into two groups: smokers (n = 351) and non-smokers (n = 398). Propensity score matching was employed to address differences in sample size and baseline demographics between the two groups (n = 274, each). Comparative analyses included assessments of oncological outcomes and complications. After matching, smoking did not significantly affect the overall complication rate (p = 0.121). Preoperative smoking did not significantly increase the occurrence of complications based on complication type (p = 0.322), nor did it increase the readmission rate (p = 0.076). There were no perioperative death in either group. Furthermore, preoperative smoking history showed no significant impact on overall survival (OS) [hazard ratio (HR) = 0.87, interquartile range (IQR): 0.54-1.42; p = 0.589] and recurrence-free survival (RFS) (HR = 1.12, IQR: 0.83-1.53; p = 0.458) following RARC for MIBC. The extent of preoperative smoking (≤ 10, 10-30, and ≥ 30 pack-years) had no significant influence on OS and RFS in any of the categories (all p > 0.05). Preoperative smoking history did not significantly affect OS, RFS, or complications in patients with MIBC undergoing RARC.

Colon cancer: the 2023 Korean clinical practice guidelines for diagnosis and treatment.

Colorectal cancer is the third most common cancer in Korea and the third leading cause of death from cancer. Treatment outcomes for colon cancer are steadily improving due to national health screening programs with advances in diagnostic methods, surgical techniques, and therapeutic agents.. The Korea Colon Cancer Multidisciplinary (KCCM) Committee intends to provide professionals who treat colon cancer with the most up-to-date, evidence-based practice guidelines to improve outcomes and help them make decisions that reflect their patients' values and preferences. These guidelines have been established by consensus reached by the KCCM Guideline Committee based on a systematic literature review and evidence synthesis and by considering the national health insurance system in real clinical practice settings. Each recommendation is presented with a recommendation strength and level of evidence based on the consensus of the committee.

Nobiletin regulates intracellular Ca2+ levels via IP3R and ameliorates neuroinflammation in Aß42-induced astrocytes.

Astrocytes are the major glial cells in the human brain and provide crucial metabolic and trophic support to neurons. The amyloid-ß peptide (Aß) alter the morphological and functional properties of astrocytes and induce inflammation and calcium dysregulation, contributing to Alzheimer's disease (AD) pathology. Recent studies highlight the role of Toll-like receptor (TLR) 4/nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling in inflammation. Reactive oxygen species (ROS) generated due to Aß, induce apoptosis in the brain cells worsening AD progression. Astrocytic cell surface receptors, such as purinergic receptors (P2Y1 and P2Y2), metabotropic glutamate receptor (mGLUR)5, α7 nicotinic acetylcholine receptor (α7nAChR), and N-methyl-d-aspartate receptors (NMDARs), have been suggested to interact with inositol trisphosphate receptor (IP3R) on the endoplasmic reticulum (ER) to induce Ca2+ movement from ER to cytoplasm, causing Ca2+ dysregulation. We found that the citrus flavonoid nobiletin (NOB) protected primary astrocytes from Aß42-induced cytotoxicity and inhibited TLR4/NF-κB signaling in Aß42-induced primary rat astrocytes. NOB was found to regulate Aß42-induced ROS levels through Keap1-Nrf2 pathway. The receptors P2Y1, P2Y2, mGLUR5, α7nAChR, and NMDARs induced intracellular Ca2+ levels by activating IP3R and NOB regulated them, thereby regulating intracellular Ca2+ levels. Molecular docking analysis revealed a possible interaction between NOB and IP3R in IP3R regulation. Furthermore, RNA sequencing revealed various NOB-mediated biological signaling pathways, such as the AD-presenilin, AD-amyloid secretase, and Wnt signaling pathway, suggesting possible neuroprotective roles of NOB. To conclude, NOB is a promising therapeutic agent for AD and works by modulating AD pathology at various levels in Aß42-induced primary rat astrocytes.

Work-related asthma in adults with severe asthma from the Korean Severe Asthma Registry (KoSAR).

Background: Exposure to allergens or irritants in the workplace may affect asthma control and the quality of life (QoL) of patients with asthma. Objective: To examine the prevalence and characteristics of work-related asthma (WRA) in adult patients with severe asthma. Methods: We analyzed data from the Korean Severe Asthma Registry (KoSAR), which is a nationwide multicenter observational study on severe asthma in Korea. Severe asthma was defined according to the American Thoracic Society (ATS) and the European Respiratory Society (ERS) guidelines. WRA was identified on the basis of asthma symptom aggravation at the workplace, as indicated by responses to a structured questionnaire. We compared the demographic and clinical characteristics and QoL between adult patients with severe asthma and WRA and those without WRA. Results: Among 364 patients with severe asthma who were employed at the time of enrollment, 65 (17.9%) had WRA. There were no significant differences in age, sex, obesity, or smoking history between the WRA and non-WRA groups. However, individuals with WRA exhibited a higher prevalence of anxiety (7.7% vs 2.4%, P = 0.046) and depression (12.3% vs 3.7%, P = 0.010) than those without. The levels of asthma control, lung function, and frequency of asthma exacerbations were similar between the two groups, but patients with WRA reported lower QoL, as determined by the Quality of Life Questionnaire for Adult Korean Asthmatics (56.6 ± 14.6 vs. 63.5 ± 13.9, P < 0.001). Conclusion: Patients with severe asthma and WRA are more likely to experience anxiety and depression and have lower QoL than those without WRA.

Discovery of Antimicrobial Agents Based on Structural and Functional Study of the Klebsiella pneumoniae MazEF Toxin-Antitoxin System.

Klebsiella pneumoniae causes severe human diseases, but its resistance to current antibiotics is increasing. Therefore, new antibiotics to eradicate K. pneumoniae are urgently needed. Bacterial toxin-antitoxin (TA) systems are strongly correlated with physiological processes in pathogenic bacteria, such as growth arrest, survival, and apoptosis. By using structural information, we could design the peptides and small-molecule compounds that can disrupt the binding between K. pneumoniae MazE and MazF, which release free MazF toxin. Because the MazEF system is closely implicated in programmed cell death, artificial activation of MazF can promote cell death of K. pneumoniae. The effectiveness of a discovered small-molecule compound in bacterial cell killing was confirmed through flow cytometry analysis. Our findings can contribute to understanding the bacterial MazEF TA system and developing antimicrobial agents for treating drug-resistant K. pneumoniae.

Colorless and transparent polyimide nanocomposites using organically modified montmorillonite and mica.

In this study, we introduce a method for replacing the glass used in existing display electronic materials, lighting, and solar cells by synthesizing a colorless and transparent polyimide (CPI) film with excellent mechanical properties and thermal stability using a combination of new monomers. Poly(amic acid) (PAA) was synthesized using dianhydride 4,4'-biphthalic anhydride (BPA) and diamine 2,2-bis(3-amino-4-hydroxyphenyl) hexafluoropropane (AHP). Various contents of organically modified montmorillonite (MMT) and mica were dispersed in PAA solution through solution intercalation, and then CPI hybrid films were prepared through multi-step thermal imidization. The organoclays synthesized to prepare CPI hybrid films were Cloisite 93A (CS-MMT) and hexadimethrine-mica (HM-Mica) based on MMT and mica, respectively. In particular, the diamine monomer AHP containing a -OH group was selected to increase the dispersibility and compatibility between the hydrophilic clays and the CPI matrix. To demonstrate the characteristics of CPI, the overall polymer structure was bent and a strong electron withdrawing -CF3 group was used as a substituent. The thermomechanical properties, morphology of clay dispersion, and optical transparency of the CPI hybrid films were investigated and compared according to the type and content of organoclays. Two types of organoclays, CS-MMT and HM-Mica, were dispersed in a CPI matrix at 1 to 7 wt%, respectively. In electron microscopy, most of the clays were uniformly dispersed in a plate-like shape of less than 20 nm at a certain critical content of the two types of organoclays, but agglomeration of the clays was observed when the content was higher than the critical content. Hybrids using HM-Mica had better thermomechanical properties and hybrids containing CS-MMT had better optical transparency.

Differential predictors of early- and delayed-onset post-traumatic stress disorder following physical injury: a two-year longitudinal study.

Objectives: This study aimed to investigate the predictors of both early- and delayed-onset PTSD over a 2-year period following physical injuries. Methods: Patients were recruited from a trauma center at a university hospital in South Korea (June 2015 ~ January 2021). At baseline, 1142 patients underwent comprehensive assessments including socio-demographic, pre-trauma, trauma-related, and peri-trauma evaluations. Diagnoses of acute stress disorder (ASD) and subthreshold ASD were also determined using the Clinician-administered PTSD Scale (CAPS). Follow-up assessments at three months included diagnoses of PTSD and subthreshold PTSD using CAPS, and stressful life events (SLEs), with additional evaluations at 6, 12, and 24 months. The analyzed sample comprised 1014 patients followed up at least once after the baseline and 3-month evaluations. PTSD diagnoses were categorized into early-onset (within the first six months after trauma) and delayed-onset (more than six months after trauma). Logistic regression models identified predictors for each group. Results: Early-onset and delayed-onset PTSD were diagnosed in 79 and 35 patients, respectively. Early-onset PTSD was predicted by previous psychiatric disorders, previous traumatic events, ASD and subthreshold ASD diagnoses, and higher anxiety levels. In contrast, delayed-onset PTSD was linked to higher education, higher injury severity, and subthreshold PTSD and SLEs at 3-month follow-up. Conclusion: Distinct predictors were found for early-onset and delayed-onset PTSD. The findings underscore the heterogeneous factors influencing the temporal development of PTSD post-trauma, and may provide valuable guidance for more targeted interventions and improved patient outcomes.