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Sung Woo Moon,1 Song Yee Kim,1 Ji Ye Jung,1 Young Ae Kang,1 Moo Suk Park,1 Young Sam Kim,1 Joon Chang,1 Jun Soo Ro,2 Yong-Ho Lee,3 Sang Hoon Lee1,4 1Division of Pulmonary Medicine, Department of Internal Medicine, Institute of Chest Diseases, Severance Hospital, Yonsei University College of Medicine, Seodaemun-gu, Seoul, Korea; 2Center for Preventive Medicine and Public Health, Seoul National University Bundang Hospital, Seongnam-si, Gyeonggi-do, Korea; 3Division of Endocrinology, Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, Seodaemun-gu, Seoul, Korea; 4Department of Internal Medicine, Division of Pulmonary and Critical Care Medicine, Seoul National University Bundang Hospital, Seongnam-si, Gyeonggi-do, Korea Purpose: Previous studies have shown that progressive forms of non-alcoholic fatty liver disease (NAFLD) occur frequently in patients with obstructive lung disease (OLD). However, few studies have written about this relationship. This study aimed to investigate the relationship between OLD and NAFLD. Subjects and methods: The Korea National Health and Nutrition Examination Survey is a national population-based, cross-sectional surveillance program that was initiated to assess the health and nutritional status of the Korean population. From 2007 to 2010, 11,738 subjects were enrolled. The subjects were defined as having NAFLD when they had scores higher than -0.640 in a NAFLD liver fat score prediction model, which was a previously validated prediction score. Individuals with forced expiratory volume in one second/forced vital capacity

PURPOSE: To determine the diagnostic performance of bedside assessment of end-tidal alveolar dead space fraction (ADSF) for pulmonary embolism (PE) and whether the use of additional ADSF assessment following D-dimer assay can improve the diagnostic accuracy in suspected PE patients in the emergency department. METHODS: A prospective observational study of 112 consecutive adult patients suspected of PE of whom 102 were eligible for analysis. ADSF was calculated using arterial carbon dioxide and end-tidal carbon dioxide. An ADSF less than 0.2 was considered normal. RESULTS: PE was confirmed in 11 (10.8%) of 102 patients. D-dimer assay alone as a reference standard test for PE had a sensitivity of 100%, specificity of 38.5% and false negativity of 0%. Area under the receiver-operator characteristic curve for the diagnosis of PE using ADSF values alone was 0.894, Sensitivity, specificity and false negativity for the combined results of a positive D-dimer test and abnormal ADSF were 100%, 78.0% and 0% for the presence of PE, respectively. Of 65 patients with a low or intermediate clinical probability and a positive D-dimer assay, 36 (55.4%) patients displayed normal ADSF and had no PE. CONCLUSIONS: By itself ADSF assessment performed well in diagnosis of PE. The combined result of a positive D-dimer and abnormal ADSF increased the specificity for diagnosing PE compared with the D-dimer test alone. The use of additional bedside ADSF assessment following a positive D-dimer test may reduce the need for further imaging studies to detect PE in patients with a low or intermediate clinical probability. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To compare the prognostic abilities of lactic acidosis and hyperlactatemia and determine the influence of metabolic acidosis when attempting to predict the outcome of septic patients using serum lactate levels. Method: 126 patients with severe sepsis or septic shock were prospectively included in this study at an emergency department. Haemodynamic variables, simplified acute physiology score (SAPS) II, arterial blood gas studies and serum lactate levels were obtained at the time of presentation (0 h) and 4 h after presentation. The probability of mortality was calculated using SAPS II scores and compared with actual inhospital mortality at different serum lactate levels and arterial pH. Survival curves for lactic acidosis and severe hyperlactatemia were analysed using the Kaplan-Meier method. RESULTS: The calculated probability of mortality decreased from 35.7% (95% CI 30.2 to 41.2) at presentation to 29.3% (95% CI 24.2 to 34.4) at 4 h post-presentation. 27.0% of patients (34) died in hospital. Arterial pH and SAPS II scores were independent factors for predicting mortality of septic patients, at 0 h and 4 h. Serum lactate levels were closely related to severity of illness and metabolic acidosis in septic patients. Patients with lactic acidosis had significantly higher inhospital mortality than patients with normal pH and normal lactate levels by Kaplan-Meier survival analysis as determined based on measurements made at 0 h and 4 h (p<0.001, p<0.001 by the log-rank test, respectively). No significant difference in survival was found between patients with hyperlactatemia and those with normal pH and serum lactate levels. CONCLUSION: Lactic acidosis not hyperlactatemia was found to predict inhospital mortality more exactly in severe sepsis and septic shock patients. The acid-base state should be considered when attempting to predict the outcome of septic patients using serum lactate levels. [ABSTRACT FROM AUTHOR]

The goal of this study was to elucidate the antiinflammatory activities of Psidium guajava L. (guava) leaf. To improve the functionality of guava leaf, it was fermented with Phellinus linteus mycelia, Lactobacillus plantarum and Saccharomyces cerevisiae. The ethanol extract from fermented guava leaf inhibited lipopolysaccharide (LPS)-induced nitric oxide (NO) and prostaglandin E(2) (PGE(2)) production. Western blot analysis showed that fermented guava leaf extract decreased LPS-induced inducible nitric oxide synthase (iNOS) and the cyclooxygenase-2 (COX-2) protein level in RAW 264.7 cells. To investigate the mechanism involved, the study examined the effect of fermented guava leaf extract on LPS-induced nuclear factor-kappaB (NF-kappaB) activation. Fermented guava leaf extract significantly inhibited LPS-induced NF-kappaB transcriptional activity. Immunochemical analysis revealed that fermented guava leaf extract suppressed LPS-induced degradation of I-kappaBalpha. Taken together, the data indicate that fermented guava leaf extract is involved in the inhibition of iNOS and COX-2 via the down-regulation of NF-kappaB pathway, revealing a partial molecular basis for the antiinflammatory properties of fermented guava leaf extract. [ABSTRACT FROM AUTHOR]

Osteoarthritis is a prevalent musculoskeletal disease that involves cartilage degradation, subchondral bone remodeling, and synovial inflammation and ultimately causes physical disability. Common risk factors for osteoarthritis include age, sex, obesity, and genetic predispositions. Treatment includes nonpharmaceutical and pharmacological approaches; however, disease-modifying osteoarthritis drugs remain undeveloped. We aimed to identify key regulatory factors underlying the etiology of osteoarthritis. We studied alterations of the inflammatory responses after manipulating the expression of MTLN, which we selected after sequencing and transcriptomics of the patients' synovial tissues. MTLN expression was increased in synovial tissues of patients and in SW982 human synovial sarcoma cells following inflammatory stimuli. We found that MTLN overexpression or knockout respectively decreased or increased expression of the inflammation-associated genes, including IL-6, IL-8, and TNF-α. Thus, high levels of MTLN in osteoarthritis may protect tissues against excessive inflammation, thereby offering therapeutic potentials., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background/Objectives : Malignant pleural effusion (MPE) in lung cancer indicates systemically disseminated advanced lung cancer and is associated with poor survival. Intrapleural hyperthermic chemotherapy (IPHC) is a promising treatment for MPE; however, its biological basis is not fully understood. IPHC can enhance anticancer drug efficacy, particularly in drug-resistant cancers. This study investigated the effects of hyperthermia on cisplatin cytotoxicity in lung cancer cell lines, patient-derived tumor cells, and a patient-derived xenograft (PDX) model. Methods : Lung cancer cell lines (A549 and H2170) and patient-derived tumor cells were cultured in 2D/3D systems and treated with cisplatin under varying temperatures (37 °C, 43 °C, and 45 °C) and exposure times (5, 15, and 30 min). Antiproliferative effects were evaluated using LDH and CCK-8 assays. Optimal conditions identified in cell culture experiments were validated using a PDX model; tumor growth inhibition, delay, and protein expression were analyzed post-treatment. Results : Hyperthermia significantly enhanced the antitumor efficacy of cisplatin at 43 °C and 45 °C, with comparable effects under 15 and 30 min exposure. In the PDX model, IPHC showed increased tumor inhibition and necrosis and delayed tumor regrowth, particularly at higher cisplatin doses. Protein expression analysis revealed that hyperthermia decreased EGFR expression and increased levels of apoptosis-related proteins, including cleaved PARP and caspase-3. Conclusions : IPHC with cisplatin demonstrated enhanced antitumor efficacy in vitro models, particularly in drug-resistant lung cancer, indicating its potential as a valuable adjunct to existing treatment regimens for lung cancer and for improving patient outcomes in advanced lung cancer with MPE or pleural metastasis.

Background: A decline in masticatory function may indicate brain dysfunction related to dementia, but the relationship between masticatory function and dementia risk remains unclear. This study aimed to investigate whether masticatory function is associated with the risk of cognitive decline and dementia., Methods: Data were obtained from the nationwide prospective cohort study of randomly sampled community-dwelling Koreans aged ≥ 60 years. The 5,064 non-demented participants, whose number of chewing cycles per bite was assessed by clinical interview, were followed for 8 years with biennial assessments of cognitive performance and clinical diagnoses of all-cause dementia and Alzheimer's disease (AD). Structural brain magnetic resonance imaging was collected from a subset of cohort participants and their spouses for imaging analyses., Results: Males who chewed ≥ 30 cycles/bite had faster decline in global cognition and memory function and were at higher risk for incident all-cause dementia (hazard ratio [HR], 2.91; 95% confidence interval [CI], 1.18-7.18) and AD (HR, 3.22; 95% CI, 1.14-9.11) compared to males with less than 10 cycles/bite. Additionally, increased chewing cycles in males were associated with reduced brain volume, particularly in regions involved in compensatory cognitive control of mastication. There was no significant association between chewing cycles and the risk of dementia or brain volume in females., Conclusion: Older men who frequently chew their meals could be considered a notable population at risk for dementia who should be carefully assessed for their cognitive trajectories., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2024 The Korean Academy of Medical Sciences.)

Opioids effectively manage perioperative pain but have numerous adverse effects. Opioid-free anesthesia (OFA) eliminates intraoperative opioid use; however, evidence for its use in video-assisted thoracoscopic surgery (VATS) is limited. This study assessed the effect of OFA using ketamine in VATS patients compared to opioid-sparing anesthesia (OSA). A total of 91 patients undergoing VATS lobectomy or segmentectomy were randomized to either the OFA group (ketamine) or the OSA group (remifentanil). The primary outcome was the quality of recovery (QoR) on postoperative day (POD) 1, measured with the QoR-40 questionnaire. Secondary outcomes included postoperative pain scores and adverse events. Both groups had comparable baseline and surgical characteristics. On POD 1, the QoR-40 score was higher in the OFA group than in the OSA group (164.3 ± 10.8 vs. 158.7 ± 10.6; mean difference: 5.6, 95% CI: 1.1, 10.0; p = 0.015), though this did not meet the pre-specified minimal clinically important difference of 6.3. The visual analog scale score was lower in the OFA group as compared to the OSA group at 0-1 h (4.2 ± 2.3 vs. 6.2 ± 2.1; p < 0.001) and 1-4 h after surgery (3.4 ± 1.8 vs. 4.6 ± 1.9; p = 0.003). The OFA group had a lower incidence of PONV (2 [4.4%] vs. 9 [19.6%]; p = 0.049) and postoperative shivering (4 [8.9%] vs. 13 [28.3%]; p = 0.030) than the OSA group at 0-1 h after surgery. Using OFA with ketamine proved feasible, as indicated by the stable intraoperative hemodynamics and absence of intraoperative awareness. Patients undergoing VATS with OFA using ketamine showed a statistically significant, but clinically insignificant, QoR improvement compared to those receiving OSA with remifentanil.

This study proposed an optimized histogel construction method for histological analysis by applying lung cancer patient-derived organoids (PDOs) to the developed histo-pillar strip. Previously, there is the cultured PDOs damage problem during the histogel construction due to forced detachment of the Matrigel spots from the 96-well plate bottom. To address this issue, we cultured PDO on the proposed Histo-pillar strips and then immersed them in 4% paraformaldehyde fixation solution to self-isolate PDO without damage. The 4 μ l patient-derived cell (PDC)/Matrigel mixtures were dispensed on the surface of a U-shaped histo-pillar strip, and the PDCs were aggregated by gravity and cultured into PDOs. Cultured PDOs were self-detached by simply immersing them in a paraformaldehyde fixing solution without physical processing, showing about two times higher cell recovery rate than conventional method. In addition, we proposed a method for embedding PDOs under conditions where the histogel temperature was maintained such that the histogel did not harden, thereby improving the problem of damaging the histogel block in the conventional sandwich histogel construction method. We performed histological and genotyping analyses using tumor tissues and PDOs from two patients with lung adenocarcinoma. Therefore, the PDO culture and improved histogel block construction method using the histo-pillar strip proposed in this study can be employed as useful tools for the histological analysis of a limited number of PDCs., (Creative Commons Attribution license.)

Background: The relationship between depression and the risk of multimorbidity progression has rarely been studied in older adults. This study was aimed to determine whether depression is associated with progression in the severity and complexity of multimorbidity, considering the influence of depression's severity and subtype., Methods: As a part of the Korean Longitudinal Study on Cognitive Aging and Dementia, this population-based cohort study followed a random sample of community-dwelling Koreans aged 60 and older for 8 years at 2-year intervals starting in 2010. Participants included those who completed mood and multimorbidity assessments and did not exhibit complex multimorbidity at the study's outset. Depression was assessed using the Geriatric Depression Scale, while multimorbidity was evaluated using the Cumulative Illness Rating Scale. The study quantified multimorbidity complexity by counting affected body systems and measured multimorbidity severity by averaging scores across 14 body systems., Findings: The 2,486 participants (age = 69.1 ± 6.5 years, 57.6% women) were followed for 5.9 ± 2.4 years. Linear mixed models revealed that participants with depression had a faster increase in multimorbidity complexity score (β = .065, SE = 0.019, p = 0.001) than those without depression, but a comparable increase in multimorbidity severity score (β = .001, SE = .009, p = 0.870) to those without depression. Cox proportional hazard models revealed that depression was associated with the risk of developing highly complex multimorbidity affecting five or more body systems, particularly in severe or anhedonic depression., Interpretation: Depression was associated with the worsening of multimorbidity in Korean older adults, particularly when severe or anhedonic. Early screening and management of depression may help to reduce the burden of multimorbidity in older adults., (Copyright © 2024 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.)

Background: Computed tomography (CT)-guided transthoracic needle biopsy (TNB) could damage lung structures and may disseminate tumor cells into the airway, blood vessels, and pleural cavity, affecting post-operative outcomes. Several studies have investigated the effects of TNB on the prognosis of patients, but the effects remain unclear. This study aimed to investigate whether TNB increases the risk of recurrence of resected stage IA non-small cell lung cancer (NSCLC)., Methods: In this retrospective study, we enrolled 1,077 patients with stage IA NSCLC who underwent curative resection from 2010 to 2020. Recurrence risk factors were evaluated using Cox regression analyses. A multiple logistic regression model, including age, sex, smoking history, total tumor size, invasive tumor size, histology, histologic differentiation, lymphatic invasion, vascular invasion, perineural invasion, and the number of harvested lymph nodes (LNs), was used to calculate the propensity score., Results: According to the pre-operative TNB, patients were classified into the no-TNB (n=823) and TNB (n=190) groups. After propensity score matching analysis, 380 patients were included in the no-TNB group (1:2 matching). Multivariable Cox analysis revealed that pre-operative TNB was a negative prognostic factor in patients with surgically resected stage IA NSCLC [hazard ratio (HR), 3.15; 95% confidence interval (CI): 1.49-6.67; P=0.003]. The 5-year locoregional and overall recurrence-free survival (RFS) rates were significantly lower in the TNB group than in the no-TNB group (88.3% vs . 96.8%, P=0.001; and 84.2% vs . 93.7%, P=0.02, respectively)., Conclusions: For patients with stage IA NSCLC, pre-operative TNB was a negative prognostic factor for recurrence. Surgical diagnosis and treatment without pre-operative tissue diagnosis may be considered first in patients with clinically early lung cancer., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-24-419/coif). The authors have no conflicts of interest to declare., (2024 Journal of Thoracic Disease. All rights reserved.)

Background: Bacteria within biofilms are thousand times more resistant to antibiotics. Neuraminidase is a crucial enzyme for bacterial adhesion and biofilm formation, it hydrolyzes glycosidic residue of glycoproteins, glycolipids, and oligosaccharides. Coreopsis lanceolata L. flowers may have a significant potential of bacterial neuraminidase (BNA) inhibition because of high natural abundance of chalcones., Purpose: The investigation of bacterial biofilm inhibitors has emerged as a novel therapeutic strategy against antibiotic resistance. Therefore, individual chalcones were isolated from C. lanceolata and their capacity to inhibit BNA and formation of Escherichia coli biofilm were evaluated., Methods: Different chromatographic techniques were used to isolate the compounds (1-12). Enzyme inhibition and detailed kinetic behavior of compounds was determined by estimation of kinetic parameters (Michaelis-Menten constants (K m ), maximum velocity (V max ), dissociation constant for binding with the free enzyme (K I ) and enzyme-substate complex (K IS )). Binding affinities (K SV ) and binding modes of inhibitors were elucidated by fluorescence quenching and molecular docking, respectively. The natural abundance of chalcones was established through UPLC-Q-TOF/MS. The most potent inhibitor (1) was tested for its ability to inhibit the formation of E. coli biofilm, which was examined by crystal violet assay, scanning electron microscope (SEM) and confocal laser scanning microscope (CLSM)., Results: A series of eight chalcones (1-8) and four chalcone glucosides (9-12), inhibited BNA in a dose-dependent manner with IC 50 of 8.3 ∼ 77.0 µM. The most potent chalcones were butein (1, IC 50 = 8.3 µM) and its glucoside 9 (IC 50 = 13.8 µM). The aglycones (1-8) showed non-competitive inhibition, while chalcone glucosides (9-12) displayed a mixed type I (K I < K IS ). Inhibitory behaviors were doubly confirmed by K SV and matched with tendency of IC 50 . The functional group responsible for BNA inhibition were disclosed as 4'-hydroxyl group on B-ring by structure activity relationship (SAR) and molecular docking experiments. Butein (1) suppressed E. coli biofilm formation by > 50 % at 100 µM according to crystal violet assay, which was confirmed by SEM and CLSM imaging., Conclusion: The results showed that chalcones (1-8) and chalcone glucosides (9-12), metabolites isolated from the flowers of C. lanceolata, had BNA inhibitory and antibiofilm formation effect on E. coli., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier GmbH.)

Background/Objectives : Pulmonary metastasis is the most prevalent type of extrahepatic hepatocellular carcinoma (HCC) metastasis. International guidelines recommend systemic treatment for patients with HCC having pulmonary metastases. However, the role of pulmonary metastasectomy (PM) remains relatively unexplored. Therefore, we assessed the survival outcomes and the factors influencing them in patients who underwent PM for metastatic HCC. Methods : Clinical data were collected from patients with HCC who underwent PM for metastasis at a single tertiary center between January 2004 and December 2022. Recurrence-free survival and overall survival were assessed using Kaplan-Meier curves. The Cox proportional hazards model was used to identify factors associated with survival outcomes. Results : Overall, 63 patients underwent PM with a median follow-up time of 84.0 months. The cumulative survival rates after the initial PM at 1, 2, and 5 years were 79.1%, 63.9%, and 35.6%, respectively. In multivariate analysis, early intrathoracic recurrence <6 months, number and size of metastases, resection margin status, and PM bilaterality were significantly associated with overall survival. A larger size of the primary HCC, increased number of repeated PM, and frequent lobectomy were more common in patients with early (<6 months) recurrence after PM than in those without early recurrence. Conclusions : PM in patients with metastatic HCC may provide acceptable survival outcomes for those with smaller, unilateral lung metastases that can be resected with generous surgical margins. However, early recurrence with reduced overall survival is likely in patients with a larger-size initial HCC after prior PM and lobectomy.

Background: Knee Osteoarthritis (OA) is a highly prevalent age-related disease. The altered kinematic pattern of the knee joint as well as the adjacent joints affects to progression of knee OA. However, there is a lack of research on how asymmetry of the hip rotation angle affects the gait pattern in knee OA patients., Research Question: What are the impacts of asymmetric hip rotation range on gait biomechanical characteristics and do the gait patterns differ between patients with knee OA and healthy elderly people?, Methods: Twenty-nine female patients with knee OA and 15 healthy female elders as control group were enrolled in this study. The spatiotemporal parameters, kinematic and kinetic data during walking were measured using a three-dimensional motion capture system. The differences between knee OA and control group were analyzed using an independent t-test., Results: The knee OA group exhibited a significant reduction in hip internal rotation range and internal/external rotation ratio on more affected side (p < 0.05). Significant differences were found in spatiotemporal parameters except to the step width. Significant reductions were also found in kinematic parameters (pelvic lateral tilt range, sagittal angle ranges in hip, knee and ankle, knee adduction mean angle). There were also significant differences in vertical ground reaction force and knee adduction moment (p < 0.05)., Conclusions: Knee OA patients have asymmetric hip rotation ranges. Especially limited hip internal rotation could lead to the reduction of pelvic lateral tilt, which may cause greater knee joint loading. Therefore, it is necessary to pay attention to recovery of hip rotation after knee surgery., (© 2024. The Author(s).)

Several fabrication methods have been developed for label-free detection in various fields. However, fabricating high-density and highly ordered nanoscale architectures by using soluble processes remains a challenge. Herein, we report a biosensing platform that integrates deep learning with surface-enhanced Raman scattering (SERS), featuring large-area, close-packed three-dimensional (3D) architectures of molybdenum disulfide (MoS 2 )-assisted gold nanoparticles (AuNPs) for the on-site screening of coronavirus disease (COVID-19) using human tears. Some AuNPs are spontaneously synthesized without a reducing agent because the electrons induced on the semiconductor surface reduce gold ions when the Fermi level of MoS 2 and the gold electrolyte reach equilibrium. With the addition of polyvinylpyrrolidone, a two-dimensional large-area MoS 2 layer assisted in the formation of close-packed 3D multistacked AuNP structures, resembling electroless plating. This platform, with a convolutional neural network-based deep learning model, achieved outstanding SERS performance at subterascale levels despite the microlevel irradiation power and millisecond-level acquisition time and accurately assessed susceptibility to COVID-19. These results suggest that our platform has the potential for rapid, low-damage, and high-throughput label-free detection of exceedingly low analyte concentrations.

Hypoxia is a representative tumor characteristic associated with malignant progression in clinical patients. Engineered in vitro models have led to significant advances in cancer research, allowing for the investigation of cells in physiological environments and the study of disease mechanisms and processes with enhanced relevance. In this study, we propose a U-shape pillar strip for a 3D cell-lumped organoid model (3D-COM) to study the effects of hypoxia on lung cancer in a high-throughput manner. We developed a U-pillar strip that facilitates the aggregation of PDCs mixed with an extracellular matrix to make the 3D-COM in 384-plate array form. The response to three hypoxia-activated prodrugs was higher in the 3D-COM than in the 2D culture model. The protein expression of hypoxia-inducible factor 1 alpha (HIF-1α) and HIF-2α, which are markers of hypoxia, was also higher in the 3D-COM than in the 2D culture. The results show that 3D-COM better recapitulated the hypoxic conditions of lung cancer tumors than the 2D culture. Therefore, the U-shape pillar strip for 3D-COM is a good tool to study the effects of hypoxia on lung cancer in a high-throughput manner, which can efficiently develop new drugs targeting hypoxic tumors.

Hybrid lateral closed-wedge high tibial osteotomy (HBHTO) carries certain advantages over medial open-wedge high tibial osteotomy (OWHTO). We investigated the potential difference in the required correction angle between HBHTO and OWHTO to achieve an equal amount of whole lower-extremity alignment correction, retrospectively analyzing the preoperative plain radiographic images of 100 patients. The medial proximal tibial angle (MPTA), joint line convergence angle (JLCA), mechanical lateral distal femoral angle (mLDFA), hip-knee-ankle axis (HKA), length of the tibia, width of the tibial plateau, length of the lower limb (leg length), and location of the center of deformity (CD) were measured. Differences in the required correction angle at the hinge point between the two techniques (CAD) were compared, and correlation analysis was performed to reveal the influential factors. The mean difference in CAD between HBHTO and OWHTO was 0.78 ± 0.22 (0.4~1.5)°, and mean WBL position change per correction angle was 3.9 ± 0.3 (3.0~4.6)% in HBHTO and 4.1 ± 0.3 (3.1~4.7)% in OWHTO. Correlation analysis revealed a strong positive correlation between CAD and HKA. mLDFA, JLCA, MPTA, leg length, OWCD, HBCD, and HCD were also significantly correlated with CAD. HBHTO required a 5.6% larger correction angle at the hinge point to achieve the same amount of alignment correction as OWHTO.

Patient-derived organoids (PDOs) are valuable in predicting response to cancer therapy. PDOs are ideal models for precision oncologists. However, their practical application in guiding timely clinical decisions remains challenging. This study focused on patients with advanced EGFR-mutated non-small cell lung cancer and employed a cancer organoid-based diagnosis reactivity prediction (CODRP)-based precision oncology platform to assess the efficacy of EGFR inhibitor treatments. CODRP was employed to evaluate EGFR-tyrosine kinase inhibitors (TKI) drug sensitivity. The results were compared to those obtained using area under the curve index. This study validated this index by testing lung cancer-derived organoids in 14 patients with lung cancer. The CODRP index-based drug sensitivity test reliably classified patient responses to EGFR-TKI treatment within a clinically suitable 10-day timeline, which aligned with clinical drug treatment responses. This approach is promising for predicting and analyzing the efficacy of anticancer, ultimately contributing to the development of a precision medicine platform., (© 2024. The Author(s).)

This study examines the efficacy of employing calcium sulfoaluminate (CSA) cement, an environmentally friendly binder, for enhancing the geomechanical characteristics of sand, particularly under low confining pressure conditions. A series of triaxial consolidated drained tests were performed on sand samples treated with varying content (5, 7, and 10%) of CSA cement and 10% ordinary Portland cement (OPC) under various low confining pressures (50, 100, 200, and 400 kPa). The test findings demonstrated the importance of cement content and confining pressure on the mode of failure, stress-strain and volumetric behavior, failure characteristics, and shear strength parameters of the treated quartz sand. After a curing period of 14 days, samples treated with 10% CSA cement exhibited a remarkable 212% increase in peak deviator stress and an 89% reduction in axial strain at failure, indicating higher initial stiffness compared to untreated samples under a 400 kPa confining pressure. Furthermore, the samples treated with 10% CSA exhibited higher peak deviator stress, initial stiffness, and strength development compared to those treated with 10% OPC. The scanning electron microscopy analysis provides insights into particle breakage and bond degradation processes, which increase with confining pressure in CSA-treated samples. Also, the mode of failure analysis reveals a transition from ductile to slightly brittle behavior with increasing cement content. Notably, the geomechanical properties of the treated material emphasized the significant impact of CSA cement on soil improvement. Thus offering a sustainable alternative for soil improvement in construction projects., (© 2024. The Author(s).)

Painful stimuli elicit first-line reflexive defensive reactions and, in many cases, also evoke second-line recuperative behaviors, the latter of which reflects the sensing of tissue damage and the alleviation of suffering. The lateral parabrachial nucleus (lPBN), composed of external- (elPBN), dorsal- (dlPBN), and central/superior-subnuclei (jointly referred to as slPBN), receives sensory inputs from spinal projection neurons and plays important roles in processing affective information from external threats and body integrity disruption. However, the organizational rules of lPBN neurons that provoke diverse behaviors in response to different painful stimuli from cutaneous and deep tissues remain unclear. In this study, we used region-specific neuronal depletion or silencing approaches combined with a battery of behavioral assays to show that slPBN neurons expressing substance P receptor ( NK1R ) (lPBN NK1R ) are crucial for driving pain-associated self-care behaviors evoked by sustained noxious thermal and mechanical stimuli applied to skin or bone/muscle, while elPBN neurons are dispensable for driving such reactions. Notably, lPBN NK1R neurons are specifically required for forming sustained somatic pain-induced negative teaching signals and aversive memory but are not necessary for fear-learning or escape behaviors elicited by external threats. Lastly, both lPBN NK1R and elPBN neurons contribute to chemical irritant-induced nocifensive reactions. Our results reveal the functional organization of parabrachial substrates that drive distinct behavioral outcomes in response to sustained pain versus external danger under physiological conditions.

Background: Unexpected conversion to thoracotomy during planned video-assisted thoracoscopic surgery (VATS) can lead to poor outcomes and comparatively high morbidity. This study was conducted to assess preoperative risk factors associated with unexpected thoracotomy conversion and to develop a risk scoring model for preoperative use, aimed at identifying patients with an elevated risk of conversion., Methods: A retrospective analysis was conducted of 1,506 patients who underwent surgical resection for non-small cell lung cancer. To evaluate the risk factors, univariate analysis and logistic regression were performed. A risk scoring model was established to predict unexpected thoracotomy conversion during VATS of the lung, based on preoperative factors. To validate the model, an additional cohort of 878 patients was analyzed., Results: Among the potentially significant clinical variables, male sex, previous ipsilateral lung surgery, preoperative detection of calcified lymph nodes, and clinical T stage were identified as independent risk factors for unplanned conversion to thoracotomy. A 6-point risk scoring model was developed to predict conversion based on the assessed risk, with patients categorized into 4 groups. The results indicated an area under the receiver operating characteristic curve of 0.747, with a sensitivity of 80.5%, specificity of 56.4%, positive predictive value of 1.8%, and negative predictive value of 91.0%. When applied to the validation cohort, the model exhibited good predictive accuracy., Conclusion: We successfully developed and validated a risk scoring model for preoperative use that can predict the likelihood of unplanned conversion to thoracotomy during VATS of the lung.

Metalenses are instruments that manipulate waves and have exhibited remarkable capabilities to date. However, an important hurdle arises due to the severe hampering of the angular response originating from coma and field curvature aberrations, which result in a loss of focusing ability. Herein, we provide a blueprint by introducing the notion of a wide field-of-hearing (FOH) metalens, designed particularly for capturing and focusing sound with decreased aberrations. Employing an aberration-free planar-thin metalens that leverages perfect acoustic symmetry conversion, we experimentally realize a robust wide FOH capability of approximately 140 ∘ in angular range. Moreover, our metalens features a relatively short focal length, enabling compact implementation by reducing the aperture-to-hearing plane distance. This is beneficial for space-efficient source-tracking sound sensing. Our strategy can be used across various platforms, potentially including energy harvesting, monitoring, imaging, and communication in auditory, ultrasonic, and submerged environments., (© 2024. The Author(s).)

The issue of rainfall-induced slope failure has attracted more attention from geotechnical engineers as a consequence of global warming. Current cumulative waste disposal has generated scientific interest in the utilization of waste materials in geotechnical design for climate change adaptation measures. Taking into consideration the effect of slope height and angle, steel slag-a waste product derived from the production of steel-was investigated as a slope cover against rainfall. To assess the stability of the slope and the infiltration of water into the soil, numerical analyses were conducted using both SEEP/W and SLOPE/W software in conjunction with rainfall conditions. Based on the findings, it can be concluded that increasing the slope's elevation and inclination will have an adverse effect on its safety factor. Steel slag can nevertheless be utilized for minimizing rainwater infiltration into the slope, as indicated by the pore-water pressure variations and graphs of the safety factor versus time. For a 20-m slope height, steel slag slopes have demonstrated a lower factor of safety difference in comparison to the initial slope without remediation. Regardless of slope angle and slope height, the safety factor reduces marginally during rainfall., (© 2024. The Author(s).)

Molecular discovery is central to the field of chemical informatics. Although optimization approaches have been developed that target-specific molecular properties in combination with machine learning techniques, optimization using databases of limited size is challenging for efficient molecular design. We present a molecular design method with a Gaussian process regression model and a graph-based genetic algorithm (GB-GA) from a data set comprising a small number of compounds by introducing mutation probability control in the genetic algorithm to enhance the optimization capability and speed up the convergence to the optimal solution. In addition, we propose reducing the number of parameters in the conventional GB-GA focusing on efficient molecular design from a small database. We generated a target-specific database by combining active learning and iterative design in the evolutionary methodologies and chose Gaussian process regression as the prediction model for molecular properties. We show that the proposed scheme is more efficient for optimization toward the target properties from goal-directed benchmarks with several drug-like molecules compared to the conventional GB-GA method. Finally, we provide a demonstration whereby we designed D-luciferin analogues with near-infrared fluorescence for bioimaging, which is desirable for effective in vivo light sources, from a small-size data set.

Background: Early non-small cell lung cancer (NSCLC) that abuts adjacent structures requires careful evaluation due to its potential impact on postoperative outcomes and prognosis. We examined stage I NSCLC with invasion into adjacent structures, focusing on the prognostic implications after curative surgical resection., Methods: We retrospectively analyzed the records of 796 patients who underwent curative surgical resection for pathologic stage IA/IB NSCLC (i.e., visceral pleural invasion only) at a single center from 2008 to 2017. Patients were classified based on tumor abutment and then reclassified by the presence of visceral pleural invasion. Clinical characteristics, pathological features, and survival rates were compared., Results: The study included 181 patients with abutting NSCLC (22.7% of all participants) and 615 with non-abutting tumors (77.3%). Those with tumor abutment exhibited higher rates of non-adenocarcinoma (26.5% vs. 9.9%, p<0.01) and visceral/lymphatic/vascular invasion (30.4%/33.1%/12.7% vs. 8.5%/22.4%/5.7%, respectively; p<0.01) compared to those without abutment. Multivariable analysis identified lymphatic invasion and male sex as risk factors for overall survival (OS) and disease-free survival (DFS) in stage I NSCLC measuring 3 cm or smaller. Age, smoking history, vascular invasion, and recurrence emerged as risk factors for OS, whereas the presence of non-pure ground-glass opacity was a risk factor for DFS., Conclusion: NSCLC lesions 3 cm or smaller that abut adjacent structures present higher rates of various risk factors than non-abutting lesions, necessitating evaluation of tumor invasion into adjacent structures and lymph node metastasis. In isolation, however, the presence of tumor abutment without visceral pleural invasion does not constitute a risk factor.

This study aimed to identify somatic mutations in nontumor cells (NSMs) in normal prostate and benign prostatic hyperplasia (BPH) and to determine their relatedness to prostate cancer (PCA). From 22 PCA patients, two prostates were sampled for 3-dimensional mapping (50 normal, 46 BPH and 1 PCA samples), and 20 prostates were trio-sampled (two normal or BPH samples and one PCA sample) and analyzed by whole-genome sequencing. Normal and BPH tissues harbored several driver NSMs and copy number alterations (CNAs), including in FOXA1, but the variations exhibited low incidence, rare recurrence, and rare overlap with PCAs. CNAs, structural variants, and mutation signatures were similar between normal and BPH samples, while BPHs harbored a higher mutation burden, shorter telomere length, larger clone size, and more private NSMs than normal prostates. We identified peripheral-zonal dominance and right-side asymmetry in NSMs, but the asymmetry was heterogeneous between samples. In one normal prostate, private oncogenic RAS-signaling NSMs were detected, suggesting convergence in clonal maintenance. Early embryonic mutations exhibited two distinct distributions, characterized as layered and mixed patterns. Our study identified that the BPH genome differed from the normal prostate genome but was still closer to the normal genome than to the PCA genome, suggesting that BPH might be more related to aging or environmental stress than to tumorigenic processes., (© 2023. The Author(s).)

Background: Visceral pleural invasion (VPI) is a poor prognostic factor that contributes to the upstaging of early lung cancers. However, the preoperative assessment of VPI presents challenges. This study was conducted to examine intraoperative pleural carcinoembryonic antigen (pCEA) level and maximum standardized uptake value (SUVmax) as predictive markers of VPI in patients with clinical T1N0M0 lung adenocarcinoma., Methods: A retrospective review was conducted of the medical records of 613 patients who underwent intraoperative pCEA sampling and lung resection for non-small cell lung cancer. Of these, 390 individuals with clinical stage I adenocarcinoma and tumors ≤30 mm were included. Based on computed tomography findings, these patients were divided into pleural contact (n=186) and non-pleural contact (n=204) groups. A receiver operating characteristic (ROC) curve was constructed to analyze the association between pCEA and SUVmax in relation to VPI. Additionally, logistic regression analysis was performed to evaluate risk factors for VPI in each group., Results: ROC curve analysis revealed that pCEA level greater than 2.565 ng/mL (area under the curve [AUC]=0.751) and SUVmax above 4.25 (AUC=0.801) were highly predictive of VPI in patients exhibiting pleural contact. Based on multivariable analysis, pCEA (odds ratio [OR], 3.00; 95% confidence interval [CI], 1.14-7.87; p=0.026) and SUVmax (OR, 5.25; 95% CI, 1.90-14.50; p=0.001) were significant risk factors for VPI in the pleural contact group., Conclusion: In patients with clinical stage I lung adenocarcinoma exhibiting pleural contact, pCEA and SUVmax are potential predictive indicators of VPI. These markers may be helpful in planning for lung cancer surgery.

StAR-related lipid transfer domain protein 8 (STARD8), encoding a Rho-GTPase-activating protein, and WNK2, encoding a serine/threonine kinase are candidate tumor suppressor genes (TSGs) in human cancers. Inactivation of these genes that would promote cancer pathogenesis is largely unknown in colon cancer (CC). Our study addressed to address whether STARD8 and WNK2 genes are mutated in CC. STARD8 and WNK2 genes possess mononucleotide repeats in their exons, which could be the targets for frameshift mutations in cancers with high microsatellite instability (MSI-H). By single-strand conformation polymorphism (SSCP) analysis, we analyzed the repeated sequences in 140 CCs (95 CCs with MSI-H and 45 CCs with stable MSI (MSS)). By DNA sequencing, we found that five MSI-H CCs (5/95: 5.3%) harbored the frameshift mutations, whereas MSS CCs (0/45) did not. In addition, we detected regional heterogeneous frameshift mutations of these genes in four (25%) of 16 MSI-H CCs. In immunohistochemistry for WNK2, WNK2 expression in the MSI-H CCs was significantly lower than that in the MSS CCs. Our results for the mutation and expression indicate that STARD8 and WNK2 genes are altered at various levels (frameshift mutation, expression, and regional heterogeneity) in MSI-H CCs, which might play a role in the pathogenesis by inactivating their TSG functions., Competing Interests: Declaration of Competing Interest There is no conflict of interest for the authors., (Copyright © 2023 Elsevier GmbH. All rights reserved.)

Background: Neuroretinitis is classically defined as a clinical triad of unilateral, painless vision loss, accompanied by optic disc edema and characteristic macular star formation. The causes of neuroretinitis can be categorized as infectious, non-infectious, and idiopathic, therefore differential diagnosis and careful evaluation are required, owing to the various etiologies and masqueraders., Case Presentation: A 54-year-old woman presented to the clinic with blurred vision in both eyes. A complete ophthalmic examination revealed optic disc edema with blurred margins and macular exudates, intraretinal edema in the temporal peripapillary area, and subretinal fluid with neurosensory retinal detachment in the macular area. Systemic laboratory investigations showed no signs of infection or inflammation. However, bone marrow suppression was suspected based on the results of the complete blood count test, and the patient was diagnosed with multiple myeloma., Conclusion: Although neuroretinitis is rarely accompanied by hematological malignancy, it is important to be mindful of the latter because ophthalmic manifestations are a common feature of hematological malignancies and lesions occur in nearly every ocular structure., (© 2023. The Author(s).)

Objective: : To investigate the relationship between reduced glutathione (GSH), a key molecule of the antioxidant defense system in the blood, and glutathione reductase (GR), which reduces oxidized glutathione (glutathione disulfide [GSSG]) to GSH and maintains the redox balance, with the prevalence of Alzheimer's dementia and cognitive decline., Methods: : In all, 20 participants with Alzheimer's dementia who completed the third follow-up clinical evaluation over 6 years were selected, and 20 participants with normal cognition were selected after age and sex matching. The GSH and GR concentrations were the independent variables. Clinical diagnosis and neurocognitive test scores were the dependent variables indicating cognitive status., Results: : The higher the level of GR, the greater the possibility of having normal cognition than of developing Alzheimer's dementia. Additionally, the higher the level of GR, the higher the neurocognitive test scores. However, this association was not significant for GSH. After 6 years, the conversion rate from normal cognition to cognitive impairment was significantly higher in the lower 50th percentile of the GR group than in the upper 50th percentile., Conclusion: : The higher the GR, the lower the prevalence of Alzheimer's dementia and incidence of cognitive impairment and the higher the cognitive test scores. Therefore, GR is a potential protective biomarker against Alzheimer's dementia and cognitive decline.

Background: Recently, cancer organoid-based drug sensitivity tests have been studied to predict patient responses to anticancer drugs. The area under curve (AUC) or IC 50 value of the dose-response curve (DRC) is used to differentiate between sensitive and resistant patient's groups. This study proposes a multi-parameter analysis method (cancer organoid-based diagnosis reactivity prediction, CODRP) that considers the cancer stage and cancer cell growth rate, which represent the severity of cancer patients, in the sensitivity test., Methods: On the CODRP platform, patient-derived organoids (PDOs) that recapitulate patients with lung cancer were implemented by applying a mechanical dissociation method capable of high yields and proliferation rates. A disposable nozzle-type cell spotter with efficient high-throughput screening (HTS) has also been developed to dispense a very small number of cells due to limited patient cells. A drug sensitivity test was performed using PDO from the patient tissue and the primary cancer characteristics of PDOs were confirmed by pathological comparision with tissue slides., Results: The conventional index of drug sensitivity is the AUC of the DRC. In this study, the CODRP index for drug sensitivity test was proposed through multi-parameter analyses considering cancer cell proliferation rate, the cancer diagnosis stage, and AUC values. We tested PDOs from eight patients with lung cancer to verify the CODRP index. According to the anaplastic lymphoma kinase (ALK) rearrangement status, the conventional AUC index for the three ALK-targeted drugs (crizotinib, alectinib, and brigatinib) did not classify into sensitive and resistant groups. The proposed CODRP index-based drug sensitivity test classified ALK-targeted drug responses according to ALK rearrangement status and was verified to be consistent with the clinical drug treatment response., Conclusions: Therefore, the PDO-based HTS and CODRP index drug sensitivity tests described in this paper may be useful for predicting and analyzing promising anticancer drug efficacy for patients with lung cancer and can be applied to a precision medicine platform., (© 2023. The Author(s).)

Endometriosis consists of ectopic endometrial epithelial cells (EEECs) and ectopic endometrial stromal cells (EESCs) mixed with heterogeneous stromal cells. To address how endometriosis-constituting cells are different from normal endometrium and among endometriosis subtypes and how their molecular signatures are related to phenotypic manifestations, we analyzed ovarian endometrial cyst (OEC), superficial peritoneal endometriosis (SPE), and deep infiltrating endometriosis (DIE) from 12 patients using single-cell RNA-sequencing (scRNA-seq). We identified 11 cell clusters, including EEEC, EESC, fibroblasts, inflammatory/immune, endothelial, mesothelial, and Schwann cells. For hormonal signatures, EESCs, but not EEECs, showed high estrogen signatures (estrogen response scores and HOXA downregulation) and low progesterone signatures (DKK1 downregulation) compared to normal endometrium. In EEECs, we found MUC5B + TFF3 low cells enriched in endometriosis. In lymphoid cells, evidence for both immune activation (high cytotoxicity in NK) and exhaustion (high checkpoint genes in NKT and cytotoxic T) was identified in endometriosis. Signatures and subpopulations of macrophages were remarkably different among endometriosis subtypes with increased monocyte-derived macrophages and IL1B expression in DIE. The scRNA-seq predicted NRG1 (macrophage)-ERBB3 (Schwann cell) interaction in endometriosis, expressions of which were validated by immunohistochemistry. Myofibroblast subpopulations differed according to the location (OECs from fibroblasts and SPE/DIEs from mesothelial cells and fibroblasts). Endometriosis endothelial cells displayed proinflammation, angiogenesis, and leaky permeability signatures that were enhanced in DIE. Collectively, our study revealed that (1) many cell types-endometrial, lymphoid, macrophage, fibroblast, and endothelial cells-are altered in endometriosis; (2) endometriosis cells show estrogen responsiveness, immunologic cytotoxicity and exhaustion, and proinflammation signatures that are different in endometriosis subtypes; and (3) novel endometriosis-specific findings of MUC5B + EEECs, mesothelial cell-derived myofibroblasts, and NRG1-ERBB3 interaction may underlie the pathogenesis of endometriosis. Our results may help extend pathologic insights, dissect aggressive diseases, and discover therapeutic targets in endometriosis. © 2023 The Pathological Society of Great Britain and Ireland., (© 2023 The Pathological Society of Great Britain and Ireland.)

Background: Given the heterogeneity of underlying lung disease and the higher morbidity and mortality associated with surgery for secondary pneumothorax (SP), treatment standardization and evidence-based early surgical management are challenging pursuits. Our aim was to document the clinical course of SP after initial surgical intervention and analyse related recurrence risk., Methods: We conducted a retrospective review of 160 patients, each with SP, using clinical records housed in an institutional database. Clinical, imaging, and operative data were retrieved, and Cox proportional hazards (PH) analysis was undertaken to identify risk factors for recurrence., Results: During a mean follow-up of 58.7 months, the overall recurrence rate in this cohort was 18.75% (ipsilateral, 14; contralateral, 16). A total of 24 patients had ≥3 ipsilateral episodes <6 months prior to surgery, marked by initial index episodes. In multivariate Cox PH analysis, the strongest risk factor for recurrence was underlying lung pathology other than chronic obstructive pulmonary disease [COPD: hazard ratio (HR) =5.3; P<0.001]., Conclusions: In this setting, underlying lung disease of a non-COPD nature is a proven risk factor for postsurgical recurrence. There is also a tendency in some patients for multiple episodes of pneumothorax within short periods of time, especially in the absence of COPD. Underlying disease processes may thus merit consideration in treatment planning., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-23-867/coif). The authors have no conflicts of interest to declare., (2023 Journal of Thoracic Disease. All rights reserved.)

This research explores the alteration of metal-organic frameworks (MOFs) using a method called postsynthetic metal exchange. We focus on the shift from a Zn-based MOF containing a [Zn 4 O(COO) 6 ] secondary building unit (SBU) of octahedral site symmetry (ANT-1(Zn)) to a Fe-based one with a [Fe 3 III O(COO) 6 ] + SBU of trigonal prismatic site symmetry (ANT-1(Fe)). The symmetry-mismatched SBU transformation cleverly maintains the MOF's overall structure by adjusting the conformation of the flexible 1,3,5-benzenetribenzoate linker to alleviate the framework strain. The process triggers a decrease in the framework volume and pore size alongside a change in the framework's charge. These alterations influence the MOF's ability to adsorb gas and dye. During the transformation, core-shell MOFs (ANT-1(Zn@Fe)) are formed as intermediate products, demonstrating unique gas sorption traits and adjusted dye adsorption preferences due to the structural modifications at the core-shell interface. Heteronuclear clusters, located at the framework interfaces, enhance the heat of CO 2 adsorption. Furthermore, they also influence the selectivity of the dye size. This research provides valuable insights into fabricating novel MOFs with unique properties by modifying the SBU of a MOF with flexible organic linkers from one site symmetry to another.

Background: Integrating a joint approach to chronic disease management within the context of a couple has immense potential as a valuable strategy for both prevention and treatment. Although spousal concordance has been reported in specific chronic illnesses, the impact they cumulatively exert on a spouse in a longitudinal setting has not been investigated. We aimed to determine whether one's cumulative illness burden has a longitudinal impact on that of their spouse., Methods: Data was acquired from a community-based prospective cohort that included Koreans aged 60 years and over, randomly sampled from 13 districts nationwide. Data from the baseline assessment (conducted from November 2010 to October 2012) up to the 8-year follow-up assessment was analyzed from October 2021 to November 2022. At the last assessment, partners of the index participants were invited, and we included 814 couples in the analysis after excluding 51 with incomplete variables. Chronic illness burden of the participants was measured by the Cumulative Illness Rating Scale (CIRS). Multivariable linear regression and causal mediation analysis were used to examine the longitudinal effects of index chronic illness burden at baseline and its change during follow-up on future index and spouse CIRS scores., Results: Index participants were divided based on baseline CIRS scores (CIRS < 6 points, n = 555, mean [SD] age 66.3 [4.79] years, 43% women; CIRS ≥ 6 points, n = 259, mean [SD] age 67.7 [4.76] years, 36% women). The baseline index CIRS scores and change in index CIRS scores during follow-up were associated with the spouse CIRS scores (β = 0.154 [SE: 0.039], p < 0.001 for baseline index CIRS; β = 0.126 [SE: 0.041], p = 0.002 for change in index CIRS) at the 8-year follow-up assessment. Subgroup analysis found similar results only in the high CIRS group. The baseline index CIRS scores and change in index CIRS scores during follow-up had both direct and indirect effects on the spouse CIRS scores at the 8-year follow-up assessment., Conclusions: The severity and course of one's chronic illnesses had a significant effect on their spouse's future chronic illness particularly when it was severe. Management strategies for chronic diseases that are centered on couples may be more effective., (© 2023. BioMed Central Ltd., part of Springer Nature.)

In Mycobacterium leprae (M. leprae)-infection, inflammatory cells' subsets and dynamics as well as the interactions with Schwann cells have remained elusive. We investigated individual cells in M. leprae-inoculated nude mice by single-cell RNA-sequencing (scRNA-seq). For macrophages, we dissected two M1-like subsets and five M2-like subsets, where lipid-associated signatures were pervasive in both M1-like and M2-like subsets. There were four macrophage trajectories showing: (i) pro-inflammatory (M1), (ii) lipid metabolism-related (M2), (iii) anti-inflammatory (M2), and (iv) interferon-stimulated gene-related (M2) fates. They displayed early divergence without ever rejoining along the paths, suggesting simultaneous or continuous stimuli for macrophage activation in leprosy. The scRNA-seq predicted Schwann cell-macrophage interactions (Notch1-Jag1, Plxnb1-Sema4d interactions). An immature Schwann cell subset showing Tfap2a expression was identified, indicating Schwann cell dedifferentiation in leprosy tissues. Expressions of Notch1, Jag1, Plxnb1, Sema4d, and Tfap2a were validated in mouse or human leprosy tissues by immunohistochemistry. We identified both pro-inflammatory and inflammation-resolution signatures, where lipid-associated signatures were pervasive to the macrophages, representing leprosy-specific macrophage states for prolonged and repeated episodes of inflammation and resolution. Our study identified refined molecular states and interactions of macrophages and Schwann cells, suggesting novel insights into the pathogenesis of unhealed inflammation with neuropathy and potential therapeutic targets for leprosy., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier GmbH. All rights reserved.)

Objectives: To evaluate the prognostic value of TLR from PET/CT in patients with resection margin-negative stage IB and IIA non-small cell lung cancer (NSCLC) and compare high-risk factors necessitating adjuvant treatment (AT)., Methods: Consecutive FDG PET/CT scans performed for the initial staging of NSCLC stage IB and IIA were retrospectively reviewed. The maximum standardized uptake value (SUVmax) of the primary tumor and mean SUV of the liver were acquired. The tumor-to-liver SUV ratio (TLR) was also calculated. Charts were reviewed for basic patient characteristics and high-risk factors for considering AT (poor differentiation, visceral pleura invasion, vascular invasion, tumors > 4 cm, and wedge resection). Statistical analysis was performed using Cox regression analysis and the Kaplan-Meier method., Results: Of the 112 patients included, 15 (13.4%) died, with a median overall survival (OS) of 43.8 months. Twenty-two patients (19.6%) exhibited recurrence, with median disease-free survival (DFS) of 36.0 months. In univariable analysis, pathology, poor differentiation, and TLR were associated with shorter DFS and OS. In multivariable analysis, TLR (hazard ratio [HR] = 1.263, p = 0.008) and differentiation (HR = 3.087, p = 0.012) were associated with shorter DFS. Also, TLR (HR = 1.422, p < 0.001) was associated with shorter OS., Conclusion: TLR from FDG PET/CT was an independent prognostic factor for recurrence and survival. PET parameters constitute risk factors for consideration in the decision-making for AT in margin-negative stage IB and IIA NSCLC., Clinical Relevance Statement: In this study, TLR from FDG PET/CT was an independent prognostic factor in stage IB-IIA non-small cell cancer patients. Although additional validation studies are warranted, TLR has the potential to be used to determine the need for adjuvant therapy., Key Points: • High TLR is an independent poor prognostic factor in stage IB-IIA NSCLC. • Adjuvant treatment should be considered in patients with high TLR following complete tumor resection., (© 2023. The Author(s), under exclusive licence to European Society of Radiology.)