Myeloid-derived suppressor cells in pleural effusion as a diagnostic marker for early discrimination of pulmonary tuberculosis from pneumonia.

Introduction: Tuberculous pleural effusion (TPE) stands as one of the primary forms of extrapulmonary tuberculosis (TB) and frequently manifests in regions with a high prevalence of TB, consequently being a notable cause of pleural effusion in such areas. However, the differentiation between TPE and parapneumonic pleural effusion (PPE) presents diagnostic complexities. This study aimed to evaluate the potential of myeloid-derived suppressor cells (MDSCs) in the pleural fluid as a potential diagnostic marker for distinguishing between TPE and PPE. Methods: Adult patients, aged 18 years or older, who presented to the emergency room of a tertiary referral hospital and received a first-time diagnosis of pleural effusion, were prospectively enrolled in the study. Various immune cell populations, including T cells, B cells, natural killer (NK) cells, and MDSCs, were analyzed in both pleural fluid and peripheral blood samples. Results: In pleural fluid, the frequency of lymphocytes, including T, B, and NK cells, was notably higher in TPE compared to PPE. Conversely, the frequency of polymorphonuclear (PMN)-MDSCs was significantly higher in PPE. Notably, compared to traditional markers such as the neutrophil-to-lymphocyte ratio and adenosine deaminase level, the frequency of PMN-MDSCs emerged as a more effective discriminator between PPE and TPE. PMN-MDSCs demonstrated superior positive and negative predictive values and exhibited a higher area under the curve in the receiver operating characteristic curve analysis. PMN-MDSCs in pleural effusion increased the levels of reactive oxygen species and suppressed the production of interferon-gamma from T cells following nonspecific stimulation. These findings suggest that MDSC-mediated immune suppression may contribute to the pathology of both TPE and PPE. Discussion: The frequency of PMN-MDSCs in pleural fluid is a clinically useful indicator for distinguishing between TPE and PPE.

Loss of SREBP-1c ameliorates iron-induced liver fibrosis by decreasing lipocalin-2.

Sterol regulatory element-binding protein (SREBP)-1c is involved in cellular lipid homeostasis and cholesterol biosynthesis and is highly increased in nonalcoholic steatohepatitis (NASH). However, the molecular mechanism by which SREBP-1c regulates hepatic stellate cells (HSCs) activation in NASH animal models and patients have not been fully elucidated. In this study, we examined the role of SREBP-1c in NASH and the regulation of LCN2 gene expression. Wild-type and SREBP-1c knockout (1cKO) mice were fed a high-fat/high-sucrose diet, treated with carbon tetrachloride (CCl4), and subjected to lipocalin-2 (LCN2) overexpression. The role of LCN2 in NASH progression was assessed using mouse primary hepatocytes, Kupffer cells, and HSCs. LCN2 expression was examined in samples from normal patients and those with NASH. LCN2 gene expression and secretion increased in CCl4-induced liver fibrosis mice model, and SREBP-1c regulated LCN2 gene transcription. Moreover, treatment with holo-LCN2 stimulated intracellular iron accumulation and fibrosis-related gene expression in mouse primary HSCs, but these effects were not observed in 1cKO HSCs, indicating that SREBP-1c-induced LCN2 expression and secretion could stimulate HSCs activation through iron accumulation. Furthermore, LCN2 expression was strongly correlated with inflammation and fibrosis in patients with NASH. Our findings indicate that SREBP-1c regulates Lcn2 gene expression, contributing to diet-induced NASH. Reduced Lcn2 expression in 1cKO mice protects against NASH development. Therefore, the activation of Lcn2 by SREBP-1c establishes a new connection between iron and lipid metabolism, affecting inflammation and HSCs activation. These findings may lead to new therapeutic strategies for NASH.

Phloroglucinol Enhances Anagen Signaling and Alleviates H2O2-Induced Oxidative Stress in Human Dermal Papilla Cells.

Phloroglucinol (PG) is one of the abundant isomeric benzenetriols in brown algae. Due to its polyphenolic structure, PG exhibits various biological activities. However, the impact of PG on anagen signaling and oxidative stress in human dermal papilla cells (HDPCs) is unknown. In this study, we investigated the therapeutic potential of PG for improving hair loss. A non-cytotoxic concentration of PG increased anagen-inductive genes and transcriptional activities of ß-Catenin. Since several anagen-inductive genes are regulated by ß-Catenin, further experiments were performed to elucidate the molecular mechanism by which PG upregulates anagen signaling. Various biochemical analyses revealed that PG upregulated ß-Catenin signaling without affecting the expression of Wnt. In particular, PG elevated the phosphorylation of protein kinase B (AKT), leading to an increase in the inhibitory phosphorylation of glycogen synthase kinase 3 beta (GSK3ß) at serine 9. Treatment with the selective phosphoinositide 3-kinase/AKT inhibitor, LY294002, restored the increased AKT/GSK3ß/ß-Catenin signaling and anagen-inductive proteins induced by PG. Moreover, conditioned medium from PG-treated HDPCs promoted the proliferation and migration of human epidermal keratinocytes via the AKT signaling pathway. Subsequently, we assessed the antioxidant activities of PG. PG ameliorated the elevated oxidative stress markers and improved the decreased anagen signaling in hydrogen peroxide (H2O2)-induced HDPCs. The senescence-associated ß-galactosidase staining assay also demonstrated that the antioxidant abilities of PG effectively mitigated H2O2-induced senescence. Overall, these results indicate that PG potentially enhances anagen signaling and improves oxidative stress-induced cellular damage in HDPCs. Therefore, PG can be employed as a novel therapeutic component to ameliorate hair loss symptoms.

Comparison of the Usefulness of Computer-Assisted Three-Dimensional Analysis and Weight-Bearing Radiographs in Ankle Osteoarthritis.

Background: To evaluate the degree of deformation in patients with ankle osteoarthritis (OA), it is essential to measure the three-dimensional (3D), in other words, stereoscopic alignment of the ankle, subtalar, and foot arches. Generally, measurement of radiological parameters use two-dimensional (2D) anteroposterior and lateral radiographs in a weight-bearing state; however, computer-aided 3D analysis (Disior) using weight-bearing cone-beam computed tomography (CBCT) has recently been introduced. Methods: In this study, we compared the 2D human radiographic method with a stereoscopic image in patients with ankle arthritis. We enrolled 57 patients diagnosed with OA (28 left and 29 right) and obtained both standing radiographs and weight-bearing CBCT. Patients were divided by the Takakura stage. The interclass correlation coefficient (ICC) for each result was confirmed. Results: On the ICC between 2D radiographs and 3D analysis, the tibiotalar surface angle and lateral talo-1st metatarsal angle showed a good ICC grade (> 0.6), while other parameters did not have significant ICC results. Three-dimension was superior to radiographs in terms of statistical significance. Conclusions: We demonstrated that 2D and stereoscopic images are useful for the diagnosis of OA. Our study also confirmed that the radiographic features affected by ankle OA varied. However, according to the results, the typical radiography is not sufficient to diagnose and determine a treatment plan for ankle OA. Therefore, the method of using 3D images should be considered.

Pan-EGFR Inhibitor Dacomitinib Resensitizes Paclitaxel and Induces Apoptosis via Elevating Intracellular ROS Levels in Ovarian Cancer SKOV3-TR Cells.

Paclitaxel is still used as a standard first-line treatment for ovarian cancer. Although paclitaxel is effective for many types of cancer, the emergence of chemoresistant cells represents a major challenge in chemotherapy. Our study aimed to analyze the cellular mechanism of dacomitinib, a pan-epidermal growth factor receptor (EGFR) inhibitor, which resensitized paclitaxel and induced cell cytotoxicity in paclitaxel-resistant ovarian cancer SKOV3-TR cells. We investigated the significant reduction in cell viability cotreated with dacomitinib and paclitaxel by WST-1 assay and flow cytometry analysis. Dacomitinib inhibited EGFR family proteins, including EGFR and HER2, as well as its downstream signaling proteins, including AKT, STAT3, ERK, and p38. In addition, dacomitinib inhibited the phosphorylation of Bad, and combination treatment with paclitaxel effectively suppressed the expression of Mcl-1. A 2'-7'-dichlorodihydrofluorescein diacetate (DCFH-DA) assay revealed a substantial elevation in cellular reactive oxygen species (ROS) levels in SKOV3-TR cells cotreated with dacomitinib and paclitaxel, which subsequently mediated cell cytotoxicity. Additionally, we confirmed that dacomitinib inhibits chemoresistance in paclitaxel-resistant ovarian cancer HeyA8-MDR cells. Collectively, our research indicated that dacomitinib effectively resensitized paclitaxel in SKOV3-TR cells by inhibiting EGFR signaling and elevating intracellular ROS levels.

Natal factors affecting developmental defects of enamel in preterm infants: a prospective cohort study.

This study investigated natal factors influencing developmental defects of enamel (DDE) in premature infants using a newly refined preterm developmental defects of enamel (PDDE) index. Dental examinations were conducted on a cohort of 118 preterm infants (average age 3.5 ± 1.4 years) to record PDDE scores, while reviewing their medical records to examine natal factors. According to the logistic regression analysis, factors related to DDE prevalence were advanced maternal age, gestational age < 28 weeks, birth weight < 1000 g, 1 min APGAR score < 7, and hospitalization period > 2 months, which were significantly higher by 2.91, 5.53, 7.63, 10.02, and 4.0 times, respectively. According to regression analysis with generalized linear models, the PDDE scores were approximately 7.65, 4.96, and 15.0 points higher in premature children diagnosed with bronchopulmonary dysplasia, intraventricular hemorrhage, and necrotizing enterocolitis, respectively. When endotracheal intubation was performed, the PDDE score was 5.06 points higher. The prevalence of PDDE was primarily observed bilaterally in the maxillary anterior teeth. Extremely preterm infants showed significantly delayed tooth eruption, suggesting that the influence of gestational age on dental development rates. Identifying the factors related to DDE in premature children can inform early dental interventions to support the oral health of high-risk children.

Understanding the effects of Haemophilus influenzae colonization on bronchiectasis: a retrospective cohort study.

BACKGROUND: Bacterial colonization is an essential aspect of bronchiectasis. Although Haemophilus influenzae is a frequent colonizer in some regions, its clinical impacts are poorly understood. This study aimed to elucidate the impact of H. influenzae colonization in patients with bronchiectasis. METHODS: This retrospective study screened adult patients diagnosed with bronchiectasis at a tertiary referral center between April 1, 2003, and May 16, 2021, in South Korea. Propensity score matching was used to match patients with and without H. influenzae colonization. We assessed the severity of bronchiectasis as per the bronchiectasis severity index, the incidence of exacerbation, differences in lung function, and all-cause mortality. RESULTS: Out of the 4,453 patients with bronchiectasis, 79 (1.8%) were colonized by H. influenzae. After 1:2 propensity score matching, 78 and 154 patients were selected from the H. influenzae colonizer and non-colonizer groups, respectively. Although there were no significant differences between the groups regarding baseline demographics, patients colonized with H. influenzae had a higher bronchiectasis severity index (median 6 [interquartile range 4-8] vs. 4 [2-7], p = 0.002), associated with extensive radiographic involvement (52.2% vs. 37.2%, p = 0.045) and mild exacerbation without hospitalization (adjusted incidence rate ratio 0.15; 95% confidence interval 0.12-0.24). Lung function and mortality rates did not reveal significant differences, regardless of H. influenzae colonization. CONCLUSION: H. influenzae colonization in bronchiectasis was associated with more severe disease and greater incidence of mild exacerbation, but not lung function and mortality. Attention should be paid to patients with bronchiectasis with H. influenzae colonization.

Tephrosin Suppresses the Chemoresistance of Paclitaxel-Resistant Ovarian Cancer via Inhibition of FGFR1 Signaling Pathway.

Ovarian cancer is the leading cause of death among gynecologic cancers. Paclitaxel is used as a standard first-line therapeutic agent for ovarian cancer. However, chemotherapeutic resistance and high recurrence rates are major obstacles to treating ovarian cancer. We have found that tephrosin, a natural rotenoid isoflavonoid, can resensitize paclitaxel-resistant ovarian cancer cells to paclitaxel. Cell viability, immunoblotting, and a flow cytometric analysis showed that a combination treatment made up of paclitaxel and tephrosin induced apoptotic death. Tephrosin inhibited the phosphorylation of AKT, STAT3, ERK, and p38 MAPK, all of which simultaneously play important roles in survival signaling pathways. Notably, tephrosin downregulated the phosphorylation of FGFR1 and its specific adapter protein FRS2, but it had no effect on the phosphorylation of the EGFR. Immunoblotting and a fluo-3 acetoxymethyl assay showed that tephrosin did not affect the expression or function of P-glycoprotein. Additionally, treatment with N-acetylcysteine did not restore cell cytotoxicity caused by a treatment combination made up of paclitaxel and tephrosin, showing that tephrosin did not affect the reactive oxygen species scavenging pathway. Interestingly, tephrosin reduced the expression of the anti-apoptotic factor XIAP. This study demonstrates that tephrosin is a potent antitumor agent that can be used in the treatment of paclitaxel-resistant ovarian cancer via the inhibition of the FGFR1 signaling pathway.

Impact of lung cancer screening with low-dose chest computed tomography on an older population: a retrospective cohort study.

Background: The older population is at high risk of lung cancer (LC). However, the importance of lung cancer screening (LCS) in this population is rarely investigated. Herein, we evaluated the effect of LCS with low-dose computed tomography (LDCT) in the older population. Methods: This retrospective cohort study was conducted in a single center and included patients aged 70-80 years who had undergone LCS with LDCT. They were categorized into the early 70s (70-74 years) and late 70s (75-80 years) groups based on their age. Using propensity score matching, the control group included patients with non-screening-detected LC from an LC cohort. LC detection, characteristics, and treatment were compared between the early and late 70s groups and between screening-detected LC and non-screening-detected LC. Results: The study included 1,281 participants who underwent LDCT for LCS, of whom 1,020 were in their early 70s and 261 in their late 70s. Among the screening groups, 87.7% of the patients were ever-smokers. The overall LC detection rate was 2.8%. Interestingly, the LC detection rate in the late 70s group was similar to that in the early 70s group (3.4% vs. 2.7%, P=0.485). Furthermore, the incidence of LC was 6.1 cases and 8.3 cases per 1,000 person-years in the early 70s and late 70s groups, respectively (P=0.428). When comparing LC characteristics, patients with screening-detected LC showed a higher proportion of stage I LC (52.8% vs. 30.6%, P=0.010) and a lower proportion of stage IV LC (19.4% vs. 42.2%, P=0.010) than those with non-screening-detected LC. Moreover, 80.6% of patients with screening-detected LC received appropriate tumor reduction treatment based on the cancer stage. Conclusions: In the older population, LCS using LDCT showed remarkable detection of LC, with a higher proportion of cases detected at an early stage.

Comprehensive Analysis of NKX3.2 in Liver Hepatocellular Carcinoma by Bigdata.

Background and Objectives: The gene NKX3.2 plays a role in determining cell fate during development, and mutations of NKX3.2 have been studied in relation to human skeletal diseases. However, due to the lack of studies on the link between NKX3.2 and cancer, we aimed to provide insights into NKX3.2 as a new prognostic biomarker for liver hepatocellular carcinoma (LIHC). Materials and Methods: The clinical significance of LIHC was investigated using open gene expression databases. We comprehensively analyzed NKX3.2 expression in LIHC using Gene Expression Profiling Interactive Analysis 2, Tumor Immune Estimation Resource (TIMER), and Kaplan-Meier plotter databases. Then, we investigated the association between NKX3.2 expression and tumor-infiltrating immune cells (TIICs). Results: NKX3.2 expression was higher in the primary tumor group compared to the normal group, and expression was higher in fibrolamellar carcinoma (FLC) compared to other subtypes. When the prognostic value of NKX3.2 was evaluated, highly expressed NKX3.2 significantly improved the overall survival and had an unfavorable prognosis. In addition, NKX3.2 expression was associated with immune cell infiltration. Patients with low gene expression and high macrophage expression had a poorer survival rate than those with low NKX3.2 and low macrophage expression (p = 0.0309). Conclusions: High NKX3.2 expression may induce poorer prognosis in LIHC. In addition, these findings can be used as basic data due to the lack of available related research. However, further in vivo studies are essential to gain a deeper understanding of the biological role of NKX3.2 in LIHC and its potential implications for cancer development and progression.

Detection of microplastic traces in four different types of municipal wastewater treatment plants through FT-IR and TED-GC-MS.

Large amounts of microplastics are discharged into wastewater treatment plants (WWTPs), from where some of them are released into natural waterbodies on account of their not being fully eliminated by WWTPs. To investigate the behavior and emission of microplastics from WWTPs, we selected four WWTPs with different treatment technologies, including anaerobic-anoxic-aerobic (A2O), sequence batch reactor (SBR), media, and membrane bioreactor (MBR). The number of microplastics detected using Fourier transform infrared (FT-IR) spectroscopy ranged from 520 to 1820 particles/L in influent and from 0.56 to 2.34 particles/L in effluent. The microplastic removal efficiencies of four WWTPs were over 99%, indicating that the type of treatment technologies did not significantly affect the removal rate of microplastics. In the unit process for each WWTP, the major stages relating to microplastic removal were the secondary clarifier and tertiary treatment processes. Most microplastics detected were categorized as fragments and fibers, while other types were hardly detected. The size of more than 80% of microplastic particles detected in WWTPs ranged between 20 and 300 µm, indicating that they were significantly smaller than the size threshold defined for microplastics. Therefore, we used thermal extraction-desorption coupled with gas chromatography-mass spectroscopy (TED-GC-MS) to evaluate the microplastic mass content in all four WWTPs, and the results were compared with those of the FT-IR analysis. In this method, only four components, namely polyethylene, polypropylene, polystyrene, and polyethylene terephthalate, were analyzed because of the analysis limitation, and the total microplastic concentration represented the sum of four components concentrations. The influent and effluent microplastic concentrations estimated by TED-GC-MS ranged from not detectable to 160 µg/L and 0.04-1.07 µg/L, respectively, indicating a correlation coefficient of 0.861 (p < 0.05) between the TED-GC-MS and FT-IR results, when compared to the combined abundance of the four microplastic components by FT-IR analysis.

Outcomes of Angular Stable Locking System in Femoral Diaphyseal Fractures of Elderly Patients: A Multicenter Comparative Study.

Background: The angular stable locking system (ASLS) was developed to provide additional stability to the distal interlocking screw of the intramedullary (IM) nail. Effects of ASLS on the treatment of femoral diaphyseal fractures in the elderly remain unknown. The aim of this study was to compare radiological outcomes of IM nailing using ASLS screws to IM nails with conventional interlocking screws in elderly patients with femoral shaft fractures. Methods: A multicenter retrospective review of 129 patients (average age, 73.5 years; 98 women and 31 men) aged 65 years or older who underwent IM nail fixation for femoral diaphyseal fractures (AO/Orthopaedic Trauma Association [OTA] classification 32) was conducted. Demographic information of patients, fracture site (subtrochanteric or shaft), fracture type (traumatic or atypical), and AO/OTA fracture classification were investigated. Reduction status was evaluated by postoperative plain radiography. Presence of union and time to union were evaluated through serial plain radiograph follow-up. Reoperation due to nonunion or implant failure was also evaluated. Results: ASLS was used in 65 patients (50.3%). A total of 118 patients (91.5%) achieved union without additional surgery and the mean union time was 31.8 ± 13.0 weeks. In terms of reduction status, angulation was greater in the group using ASLS. There were no statistically significant differences of union rate, time to union, and reoperation rate according to the use of ASLS (p > 0.05). There was no difference in the outcomes according to the use of ASLS even when the analysis was divided in terms of fracture site or fracture type (p > 0.05). In further subgroup analysis, only the traumatic subtrochanteric area group showed statistically significantly shorter time to union when ASLS was used (p = 0.038). Conclusions: In geriatric patients with femoral diaphyseal fractures, the use of ASLS was not considered to have a significant effect on fracture healing. Fracture healing seemed to be more affected by surgical techniques such as minimizing the gap and fracture characteristics such as atypical femoral fractures, rather than implants.

RPL27 contributes to colorectal cancer proliferation and stemness via PLK1 signaling.

Although expression of ribosomal protein L27 (RPL27) is upregulated in clinical colorectal cancer (CRC) tissue, to the best of our knowledge, the oncogenic role of RPL27 has not yet been defined. The present study aimed to investigate whether targeting RPL27 could alter CRC progression and determine whether RPL27 gains an extra­ribosomal function during CRC development. Human CRC cell lines HCT116 and HT29 were transfected with RPL27­specific small interfering RNA and proliferation was assessed in vitro and in vivo using proliferation assays, fluorescence­activated cell sorting (FACS) and a xenograft mouse model. Furthermore, RNA sequencing, bioinformatic analysis and western blotting were conducted to explore the underlying mechanisms responsible for RPL27 silencing­induced CRC phenotypical changes. Inhibiting RPL27 expression suppressed CRC cell proliferation and cell cycle progression and induced apoptotic cell death. Targeting RPL27 significantly inhibited growth of human CRC xenografts in nude mice. Notably, polo­like kinase 1 (PLK1), which serves an important role in mitotic cell cycle progression and stemness, was downregulated in both HCT116 and HT29 cells following RPL27 silencing. RPL27 silencing reduced the levels of PLK1 protein and G2/M­associated regulators such as phosphorylated cell division cycle 25C, CDK1 and cyclin B1. Silencing of RPL27 reduced the migration and invasion abilities and sphere­forming capacity of the parental CRC cell population. In terms of phenotypical changes in cancer stem cells (CSCs), RPL27 silencing suppressed the sphere­forming capacity of the isolated CD133+ CSC population, which was accompanied by decreased CD133 and PLK1 levels. Taken together, these findings indicated that RPL27 contributed to the promotion of CRC proliferation and stemness via PLK1 signaling and RPL27 may be a useful target in a next­generation therapeutic strategy for both primary CRC treatment and metastasis prevention.

Nodakenin Inhibits Melanogenesis Via the ERK/MSK1 Signaling Pathway.

The aim of the present study was to investigate the potential inhibitory effects of nodakenin, a coumarin glucoside derivative from the root extract of Angelica gigas Nakai (AGN), on melanogenesis and its underlying mechanisms in B16F10 melanoma cells. The inhibitory effects of nodakenin on melanogenesis were evaluated by determining melanin contents and tyrosinase activity in α -melanocyte stimulating hormone (α-MSH)-treated B16F10 melanoma cells. The mechanisms associated with the anti-pigmentation effect of nodakenin were investigated by quantitative real-time PCR and immunoblotting analysis. Using the UVB-irradiated conditioned media culture system and UVB-irradiated co-cultivation system of HaCaT keratinocytes and B16F10 melanoma cells mimicking in vivo melanin biosynthesis, the effect of nodakenin on melanin production was evaluated. Melanin content analysis showed that nodakenin decreased cellular melanin biosynthesis in α-MSH-treated B16F10 cells. Immunoblotting revealed that CREB phosphorylation, MITF, a mastering transcription factor of melanogenesis and its downstream genes tyrosinase, tyrosinase-related protein 1, and tyrosinase-related protein 2 were downregulated by nodakenin in a dose-dependent manner. Interestingly, nodakenin did not affect the phosphorylation of PKA and p38 MAPK but the phosphorylation of ERK1/2 and MSK1. In addition, the inhibition of melanin accumulation by nodakenin in the UVB-irradiated conditioned media culture system and UVB-irradiated co-cultivation system of HaCaT and B16F10 cells suggests that nodakenin has potential as an anti-pigmentation activity. These data suggest that nodakenin inhibits the melanogenesis in B16F10 cells by interfering the ERK/ MSK1/CREB axis and thus preventing MITF expression.

Electromagnetic Navigation Bronchoscopy Versus Radial Endobronchial Ultrasound for Diagnosing Lung Cancer: A Propensity Score-Matched Analysis.

INTRODUCTION: Electromagnetic navigation bronchoscopy (ENB) and radial endobronchial ultrasound (R-EBUS) are advanced imaging-guided bronchoscopy techniques for diagnosing pulmonary lesions. This study aimed to determine the comparative diagnostic yield of sole ENB and R-EBUS under moderate sedation. METHODS: We investigated 288 patients who underwent sole ENB (n=157) or sole R-EBUS (n=131) under moderate sedation for pulmonary lesion biopsy between January 2017 and April 2022. After a 1:1 propensity score-matching to control for pre-procedural factors, the diagnostic yield, sensitivity for malignancy, and procedure-related complications between both techniques were compared. RESULTS: The matching resulted in 105 pairs/procedure for analyses with balanced clinical and radiological characteristics. The overall diagnostic yield was significantly higher for ENB than for R-EBUS (83.8% vs. 70.5%, p=0.021). ENB demonstrated a significantly higher diagnostic yield than R-EBUS among those with lesions>20mm in size (85.2% vs. 72.3%, p=0.034), radiologically solid lesions (86.7% vs. 72.7%, p=0.015), and lesions with a class 2 bronchus sign (91.2% vs. 72.3%, p=0.002), respectively. The sensitivity for malignancy was also higher for ENB than for R-EBUS (81.3% vs. 55.1%, p<0.001). After adjusting for clinical/radiological factors in the unmatched cohort, using ENB over R-EBUS was significantly associated with a higher diagnostic yield (odd ratio=3.45, 95% confidence interval=1.75-6.82). Complication rates for pneumothorax did not significantly differ between ENB and R-EBUS. CONCLUSION: ENB demonstrated a higher diagnostic yield than R-EBUS under moderate sedation for diagnosing pulmonary lesions, with similar and generally low complication rates. Our data indicate the superiority of ENB over R-EBUS in a least-invasive setting.

Effectiveness and Safety of Recombinant Human Follicle-Stimulating Hormone (Follitrope™) in Inducing Controlled Ovarian Stimulation in Infertile Women in Real-World Practice: a Prospective Cohort Study.

To evaluate the safety and effectiveness of recombinant human follicle-stimulating hormone (rhFSH [Follitrope™]) in infertile women undergoing in vitro fertilization (IVF). To identify predictors of ovarian response that induce optimal clinical outcomes. This multicenter prospective study enrolled infertile women who were scheduled to undergo IVF after ovarian stimulation with rhFSH (Follitrope™) following the gonadotropin-releasing hormone (GnRH) agonist or GnRH antagonist protocol. Predictive factors for ovarian response were identified in the GnRH antagonist group based on the number of oocytes retrieved. A total of 516 infertile women were enrolled, among whom 136 (except one who withdrew before administration) received rhFSH using the GnRH agonist protocol and 379 using the antagonist protocol. The mean number of oocytes retrieved was 13.4 in the GnRH agonist group and 13.6 in the GnRH antagonist group. The clinical pregnancy rates were 32.3% (30/93) and 39.9% (115/288) in the GnRH agonist and antagonist groups, respectively. The incidence of ovarian hyperstimulation syndrome was 1.8% and 3.4% in the GnRH agonist and antagonist groups, respectively. No other significant safety risks associated with rhFSH administration were identified. Body mass index, basal serum FSH and anti-Müllerian hormone levels, and antral follicle count were identified as predictors of ovarian response by multiple regression with backward elimination, and the final regression model accounted for 26.5% of the response variability. In real-world practice, rhFSH (Follitrope™) is safe and effective in inducing ovarian stimulation in infertile women. Patient characteristics identified as predictors can be considered to be highly related to optimal clinical outcomes.

TPX2 Amplification-Driven Aberrant Mitosis in Culture Adapted Human Embryonic Stem Cells with gain of 20q11.21.

BACKGROUND: Despite highly effective machinery for the maintenance of genome integrity in human embryonic stem cells (hESCs), the frequency of genetic aberrations during in-vitro culture has been a serious issue for future clinical applications. METHOD: By passaging hESCs over a broad range of timepoints (up to 6 years), the isogenic hESC lines with different passage numbers with distinct cellular characteristics, were established. RESULT: We found that mitotic aberrations, such as the delay of mitosis, multipolar centrosomes, and chromosome mis-segregation, were increased in parallel with polyploidy compared to early-passaged hESCs (EP-hESCs) with normal copy number. Through high-resolution genome-wide approaches and transcriptome analysis, we found that culture adapted-hESCs with a minimal amplicon in chromosome 20q11.21 highly expressed TPX2, a key protein for governing spindle assembly and cancer malignancy. Consistent with these findings, the inducible expression of TPX2 in EP-hESCs reproduced aberrant mitotic events, such as the delay of mitotic progression, spindle stabilization, misaligned chromosomes, and polyploidy. CONCLUSION: These studies suggest that the increased transcription of TPX2 in culture adapted hESCs could contribute to an increase in aberrant mitosis due to altered spindle dynamics.

Mitochondria in reproduction.

In reproduction, mitochondria produce bioenergy, help to synthesize biomolecules, and support the ovaries, oogenesis, and preimplantation embryos, thereby facilitating healthy live births. However, the regulatory mechanism of mitochondria in oocytes and embryos during oogenesis and embryo development has not been clearly elucidated. The functional activity of mitochondria is crucial for determining the quality of oocytes and embryos; therefore, the underlying mechanism must be better understood. In this review, we summarize the specific role of mitochondria in reproduction in oocytes and embryos. We also briefly discuss the recovery of mitochondrial function in gametes and zygotes. First, we introduce the general characteristics of mitochondria in cells, including their roles in adenosine triphosphate and reactive oxygen species production, calcium homeostasis, and programmed cell death. Second, we present the unique characteristics of mitochondria in female reproduction, covering the bottleneck theory, mitochondrial shape, and mitochondrial metabolic pathways during oogenesis and preimplantation embryo development. Mitochondrial dysfunction is associated with ovarian aging, a diminished ovarian reserve, a poor ovarian response, and several reproduction problems in gametes and zygotes, such as aneuploidy and genetic disorders. Finally, we briefly describe which factors are involved in mitochondrial dysfunction and how mitochondrial function can be recovered in reproduction. We hope to provide a new viewpoint regarding factors that can overcome mitochondrial dysfunction in the field of reproductive medicine.