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Cracks in solid-state materials are typically irreversible. Here we report electrically reversible opening and closing of nanoscale cracks in an intermetallic thin film grown on a ferroelectric substrate driven by a small electric field (~0.83 kV/cm). Accordingly, a nonvolatile colossal electroresistance on-off ratio of more than 108 is measured across the cracks in the intermetallic film at room temperature. Cracks are easily formed with low-frequency voltage cycling and remain stable when the device is operated at high frequency, which offers intriguing potential for next-generation high-frequency memory applications. Moreover, endurance testing demonstrates that the opening and closing of such cracks can reach over 107 cycles under 10-μs pulses, without catastrophic failure of the film.

BACKGROUND: O (6) -methylguanine-DNA methyltransferase (MGMT) is a specific DNA direct reversal repair protein which ameliorates mutagenic, carcinogenic and cytotoxic adducts from O(6) -methylguanine in DNA. The aim of this study was to investigate the potential association between six polymorphisms in the coding region of the MGMT gene and oral cancer risk in Taiwanese population. METHODS: In this hospital-based case-control study, the MGMT genotypes were determined by using DNA sequencing in 176 patients with oral squamous cell carcinoma (OSCC), 77 patients with oral premalignant lesions and 110 normal individuals. RESULTS: Although L53L and L84F polymorphisms were in complete linkage disequilibrium, no statistically significant association was found between the MGMT genotypes and haplotypes and oral cancer risk. We could also not detect any variations in the codon 65, 143, 160 and 178 within the coding region of the MGMT gene in both patients and controls. After stratification of OSCC patients by their mean age (54 years old), however, a higher overall survival rate with CT genotype than CC genotypes of the L53L polymorphisms was found in older patients (P=0.031). A borderline significance (P=0.074) between these genotypes and recurrence-free survivals has also been noted. The same results were also observed in L84F polymorphism. CONCLUSIONS: The present study did not find statistically significant association between six common MGMT polymorphisms and oral cancer risk, however, both MGMT L53L and L84F polymorphisms in old patients with CT genotype have higher overall survival rates than patients with CC genotype. Because of limited power of the present study, further study may be warranted in ethnically different populations to explore outcomes of these polymorphisms in the oral cancer risk. [ABSTRACT FROM AUTHOR]

Keloids result from pathological wound healing responses. However, the pathogenesis of keloids is still poorly understood. PGE2 was shown to decrease fibroblast proliferation, inhibit collagen synthesis and enhance the expression of matrix-metalloproteinases (MMPs). This study sought to delineate the production of PGE2 by normal and keloid-derived dermal fibroblasts. Human normal and keloid dermal fibroblasts were cultured in vitro. Cell proliferation and viability were determined based on WST-1 assay. IL-1beta-induced PGE2 production and effects of PGE2 on the synthesis of procollagen by culture-derived fibroblasts were determined by using enzyme-linked immunosorbant assay (ELISA) kits. IL-1beta-induced MMP-1 production by culture-derived fibroblasts was determined with an MMP-1 immunoassay kit. Our results showed that normal and keloid-derived fibroblasts exhibited a statistically significant increase (p<0.05) in cell proliferation when the cells were cultured in media with an increase in the concentrations (0%, 2% and 10%) of fetal bovine serum (FBS). In culture medium without FBS, an increase in cell proliferation of keloid-derived fibroblasts was detectable when compared with those of control fibroblasts. IL-1beta (1 ng/ml and 10 ng/ml) stimulated statistically significant production (p<0.01) of PGE2 by both normal and keloid-derived fibroblasts. However, lower levels of PGE2 produced by keloid-derived fibroblasts were detectable compared with those produced by normal-derived fibroblasts (p<0.05). In this study, although not statistically significant, inhibition of procollagen production by PGE2 in a dose-dependent manner was found. In addition, decreased production of MMP-1 by keloid-derived fibroblasts compared with those of control fibroblasts was also observed. In conclusion, keloid-derived fibroblasts produced less PGE2 than those produced by control fibroblasts. The role of diminished capacity of PGE2 production in keloid formation is presently unknown and needs further study. [ABSTRACT FROM AUTHOR]

Lung cancer is the most common cause of cancer mortality globally, and the prevalence of lung adenocarcinoma (LUAD), the most common lung cancer subtype, has increased sharply in East Asia. Early diagnosis leads to better survival rates, but this requires an improved understanding of the molecular changes during early tumorigenesis, particularly in non-smokers. Here, we performed whole exome-sequencing and RNA-sequencing of samples from 94 East Asian patients with precancerous lesions (25 with atypical adenomatous hyperplasia [AAH]; 69 with adenocarcinoma in situ [AIS]) and 73 patients with early invasive lesions (minimally invasive adenocarcinoma [MIA]). Cellular analysis revealed that the activities of endothelial and stromal cells could be used to categorize tumors into molecular subtypes within pathologically defined types of lesions. The subtypes were linked with the radiologically defined type of lesions and corresponded to immune cell infiltration throughout the early progression of LUAD. Spatial transcriptomic analysis revealed the distribution of epithelial cells, endothelial cells, fibroblasts, and plasma cells within MIA samples. Characterization of the molecular lesion subtypes identified positively selected mutational patterns and suggested that angiogenesis in the late-stage AIS type potentially contributes to tissue invasion of the MIA type. This study offers a resource that may help to improve early diagnosis and patient prognosis, and the findings suggest possible approaches for early disease interception.

Objectives: Myelin oligodendrocyte glycoprotein antibody disease (MOGAD) has an expanding phenotype. We describe two cases of MOGAD with associated severe intracranial hypertension. Case 1: A 21-year-old male presented with diffuse cortical encephalitis and intracranial hypertension with both serum and CSF MOG antibody positivity. Initial brain CT scan was normal but subsequent demyelination was evident on MRI. Case 2: A 44-year-old female presented with a progressive brainstem encephalitis and intracranial hypertension and normal MRI, with later development of subcortical demyelination which was confirmed on brain biopsy. CSF-restricted MOG antibody was detected following the biopsy results., Results: Both patients presented with clinical features of severe intracranial hypertension requiring surgical management followed by immunosuppressive therapy (methylprednisone and plasma exchange; and intravenous immunoglobulin and plasma exchange) leading to clinical improvement., Discussion: MOGAD should be in the differential diagnosis of acute severe intracranial hypertension even in the absence of demyelination on initial neuroimaging. Clinicians should be alert of this syndrome that requires combined management of intracranial pressure in addition to early and intensive immunotherapy., Competing Interests: Declaration of competing interest On behalf of all authors, the corresponding author states that there is no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Purpose: Clinical shadowing(CS) offers preclinical medical students the opportunity to observe certified physicians in practice. Analyzing the content of students' reflective writings(RWs) to understand core competencies they perceived during CS, as well as stages of their reflections, can offer valuable insights for course design and instructor guidance. This study aimed to address this matter by employing a thematic analysis of students' RWs to explore the learning outcomes derived from CS., Materials and Methods: The dataset of the thematic analysis comprised de-identified RWs from preclinical medical students who participated in the clinical shadowing program during the first semester of the 2019 academic year at National Taiwan University College of Medicine. Two researchers independently extracted and categorized pertinent content from the texts of RWs, aligning them with the six core competencies of ACGME and mapping them to the stages of Kolb's learning cycle. Additionally, correlation with shadowing specialties and fields was investigated., Results: In total, 155 RWs were analyzed. Patient care emerged as the most frequently reflected competency(30%), followed by systems-based practice(23%), and medical knowledge(21%). The shadowing specialties and fields had an impact on the core competencies students perceived. In terms of Kolb's learning stages, concrete experience(66%) predominated in RWs, while abstract conceptualization(19%) and reflective observation(14%) were less prevalent. For each competency, concrete experience was the prevailing stage, with active experimentation being the least dominant one. Students exhibited varying proportions of reflections at different stages for each core competency., Conclusions: Clinical shadowing experiences enable preclinical medical students to explore required clinical core competencies, with emphases depending on the shadowing specialties and fields. Currently, most reflections are concentrated at Kolb's concrete experience stage. This study offers valuable insights for designing future CS programs and improving faculty development, aimed at helping students achieve deeper and more comprehensive reflective learning in relation to core competencies, and even professional identity.

Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is facilitated by its trimeric surface spike protein, which binds to the human angiotensin-converting enzyme 2 (hACE2) receptor. This critical interaction facilitates viral entry and is a primary target for therapeutic intervention against COVID-19. However, it is difficult to fully optimize viral infection using existing protein-protein interaction methods. Herein, we introduce a nano-luciferase binary technology (NanoBiT)-based pseudoviral sensor designed to stimulate the dynamics of viral infection in both living cells and animals. Infection progression can be dynamically visualized via a rapid increase in luminescence within 3 h using an in vivo imaging system (IVIS). Inhibition of viral infection by baicalein and baicalin was evaluated using a NanoBiT-based pseudoviral sensor. These results indicate that the inhibitory efficacy of baicalein was strengthened by targeting the spike protein, whereas baicalin targeted the hACE2 protein. Additionally, under optimized conditions, baicalein and baicalin provided a synergistic combination to inhibit pseudoviral infection. Live bioluminescence imaging was used to evaluate the in vivo effects of baicalein and baicalin treatment on LgBiT-hACE2 mice infected with the BA.2-SmBiT spike pseudovirus. This innovative bioluminescent system functions as a sensitive and early-stage quantitative viral transduction in vitro and in vivo. This platform provides novel opportunities for studying the molecular biology of animal models., 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 B.V. All rights reserved.)

Background: Sarcomas are rare malignancies, accounting for approximately 1% of all cancers. Pulmonary metastases are the most preferential site for distant metastasis in malignant soft tissue sarcomas. Despite the lack of evidence from large randomized trials to support treatment guidelines, surgical resection of resectable metastatic tumors remains the current standard of care. This study aimed to explore the survival status of patients with soft tissue sarcoma after resection of pulmonary metastases., Methods: This study is a retrospective analysis of patients who mestastasectomy by means of lobar or sublobar resections at National Taiwan University Hospital and its branches. The statistical and investigation period was from February 2007 to December 2020., Results: Among 110 samples during the investigation period, the overall 5-year survival rate was 62.9%, which was higher than the 15%-50.9% reported previously. A disease-free interval of more than 12 months and the occurrence of local recurrence of sarcoma at the time of resection of pulmonary metastases are associated with overall survival. Most of the samples were treated with minimally invasive surgery (VATS), and therefore, most patients had a shorter hospital stay and better postoperative recovery., Conclusion: For pulmonary metastatic sarcoma, pulmonary metastasectomy is a relatively safe treatment method with short hospital stay and short ICU stay. The results of this study suggest that VATS is preferred over thoracotomy, but further observations are needed to confirm these findings., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Chang, Chiang, Lin, Kuo, Huang, Hsu and Chen.)

The stimulator of interferon genes (STING) pathway is crucial for tumor immunity, leading to the exploration of STING agonists as potential immunotherapy adjuvants. However, their clinical application faces obstacles including poor pharmacokinetics, transient activation, and an immunosuppressive tumor microenvironment (TME). Addressing these limitations, our study aims to develop an injectable silk fibroin hydrogel-based in situ vaccine. It incorporates a nanoscale STING agonist, an immunogenic cell death (ICD) inducer, and an immunomodulator to ensure their controlled and sustained release. cGAMP nanoparticles (cGAMPnps) with a core-shell structure ensure optimal delivery of cGAMP to dendritic cells (DCs), thereby activating the STING pathway and fostering DC maturation. ICD-associated damage-associated molecular patterns amplify and prolong STING activation via enhanced type I IFN and other inflammatory pathways, along with delayed degradation of cGAMP and STING. Furthermore, the STING-driven vascular normalization by cGAMPnps and ICD, in conjunction with immunomodulators like antiprogrammed cell death protein 1 antibody (anti-PD-1 Ab) or OX40 ligand (OX40L), effectively remodels the immunosuppressive TME. This in situ gel vaccine, when used independently or with surgery as neoadjuvant/adjuvant immunotherapy, enhances DC and CD8 + T-cell activation, suppressing tumor progression and recurrence across various immunologically cold tumor models. It revolutionizes the application of STING agonists in cancer immunotherapy, offering substantial promise for improving outcomes across a broad spectrum of malignancies.

Background: Lobectomies are the standard surgical intervention for lung cancer; however, recently, surgeons have considered segmentectomies for smaller tumors, with their potential for favorable survival outcomes while preserving lung function. The surgical outcomes of trisegmentectomies/lingulectomies and lobectomies for clinical stage I left upper lobe (LUL) non-small cell lung cancers (NSCLCs) remain undetermined. Thus, our study aimed to assess the differences between the short-term surgical and long-term survival outcomes in patients with clinical stage I LUL NSCLC who underwent trisegmentectomies/lingulectomies and those who underwent lobectomies., Methods: Between 2011 and 2021, we retrospectively reviewed the data of 377 patients with clinical stage I NSCLC who had undergone LUL lobectomies or trisegmentectomies/lingulectomies. Patients were categorized into two subcohorts according to tumor size, i.e. 0-2 and 2-4 cm. To ensure preoperative demographic comparability, 1:1 propensity-score matching (PSM) was performed., Results: This study focused on the 2-4 cm subcohort. Post-PSM, patients who underwent trisegmentectomies/lingulectomies had quicker operations and shorter postoperative hospital and intensive care unit lengths of stay than those who underwent lobectomies. Post-PSM, no statistically significant differences in progression-free survival (PFS) or overall survival (OS) were observed between the segmentectomy and lobectomy groups in both the 0-2 and 2-4 cm subcohorts. The multivariate analysis revealed that different surgical methods were not statistically significant factors for either PFS or OS., Conclusions: Trisegmentectomies/lingulectomies are a feasible option for clinical stage I NSCLC, with better perioperative outcomes and similar survival rates when compared with LUL lobectomies., (© 2024. Society of Surgical Oncology.)

Background: Collaborative learning is an essential pedagogy in medical education, within which small group learning constitutes an integral component. Online small group teaching has been widely applied and blended with in-person sessions in the aftermath of the Covid-19 pandemic. This study examined whether group metacognition was associated with teamwork satisfaction in an online small group teaching curriculum for medical students., Methods: We enrolled medical students of the 2nd and 4th years during the 2021 fall semester after they participated in 3 consecutive sessions of online small group tutorials (SGTs), which have been implemented in our medical school for more than 20 years. The students completed a group metacognitive scale (GMS) and a teamwork satisfaction scale (TSS) after the sessions. We analyzed whether group metacognition in 4 dimensions (knowledge of cognition, planning, evaluating, and monitoring) could be connected with medical students' teamwork satisfaction using partial least squares-structural equation modeling (PLS-SEM)., Results: A total of 263 medical students participated in this study. Both GMS and TSS exhibited good reliability and validity. Three of the 4 dimensions of group metacognition (cognition, planning, and evaluating) positively correlated with teamwork satisfaction (path coefficients 0.311, 0.279, and 0.21; p = 0.002, 0.002, and 0.043, respectively) following the online SGT curriculum, whereas the monitoring dimension did not (path coefficient 0.087; p = 0.357). The model achieved an adjusted R square of 0.683., Conclusion: We discovered that group metacognition correlated positively with better teamwork satisfaction, supporting the importance of group metacognitive competency for online collaborative learning., (© 2024. The Author(s).)

Introduction: Cytokines such as tumor necrosis factor-alpha (TNF-α), interleukin 6 (IL6), interferon-gamma (IFN-γ), interleukin 17-alpha (IL17-α), and interleukin 33 (IL33) play critical roles in immune responses and may impact cancer prognosis in future. However, few studies have simultaneously explored the prognostic impact of these cytokines for cancer. In this study, we aim to apply the unsupervised clustering analysis to approach the correlation between the expression of these cytokines and the subsequent prognosis of patients with esophageal squamous cell carcinoma (ESCC)., Methods: A robust clustering algorithm was used, the Gaussian mixture method (GMM), through the mclust R package to group patients based on the expression of their cytokines in plasma or tumors. The 324 NTU patients were grouped into 4 clusters, and the 179 GSE53625 patients were grouped into 3 clusters based on expression in plasma and tumors, respectively. Five- and 3-year overall survival (OS) and progression-free survival (PFS) curves of each cluster were compared. Univariate and multivariate Cox regression analyses were also performed., Results: We successfully distinguished the multimodal distribution of cytokines through GMM clustering and discovered the relationship between cytokines and clinical outcomes. We observed that NTU-G3 and NTU-G4 subgroups showed most variation in 5-, 3-year OS and 5-, 3-year PFS with NTU-G3 being associated with poorer prognosis compared to NTU-G4 (p = 0.016, 0.0052, 0.0575, and 0.0168, respectively). NTU-G3 was characterized with higher TNF-α (median = 3.855, N = 78) and lower IL33 (median = 0.000, N = 78), while NTU-G4 showed lower TNF-α (median = 1.76, N = 51) and higher IL33 (median = 1.070, N = 51). The difference was statistically significant for TNF-α and IL33, with p = 0.0002 and p &lt; 0.0001, respectively. A multivariate Cox-regression analysis revealed that GMM clustering and T/N stage were independent factors for prognosis, suggesting that the prognosis might be dependent on these cytokines., Conclusions: Our data suggest that expression patterns of IL33 and TNF-α in plasma might serve as a convenient marker to predict the prognosis of ESCC in the future., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

Introduction: Primary dysmenorrhea (PDM), characterized by cyclic pain, may involve pain modulation within the reward system (RS). The Catechol-O-methyltransferase ( COMT ) Val158Met polymorphism, which significantly influences dopamine activity, is linked to the regulation of both acute and chronic pain. This study examines the differential neurodynamic modulation in the RS associated with COMT Val158Met polymorphisms during menstrual pain among PDM subjects., Method: Ninety-one PDM subjects underwent resting-state fMRI during menstruation and were genotyped for COMT Val158Met polymorphisms. The amplitude of low-frequency fluctuation (ALFF) and functional connectivity (FC) analyses were used to assess the RS response. Psychological evaluations included the McGill Pain Questionnaire, Pain Catastrophizing Scale, Beck Anxiety Inventory, and Beck Depression Inventory., Result: Val/Val homozygotes ( n = 50) and Met carriers ( n = 41) showed no significant differences in McGill Pain Questionnaire, Beck Anxiety Inventory, and Beck Depression Inventory. However, Met carriers exhibited lower scores on the Pain Catastrophizing Scale. Distinct FC patterns was observed between Val/Val homozygotes and Met carriers, specifically between the nucleus accumbens (NAc) and prefrontal cortex, NAc and inferior parietal lobe, ventral tegmental area (VTA) and prefrontal cortex, VTA and precentral gyrus, and VTA and superior parietal lobe. Only Met carriers showed significant correlations between ALFF and FC values of the NAc and VTA with pain-related metrics (McGill Pain Questionnaire and Pain Catastrophizing Scale scores). NAc ALFF and NAc-prefrontal cortex FC values positively correlated with pain-related metrics, while VTA ALFF and VTA-prefrontal cortex and VTA-superior parietal lobe FC values negatively correlated with pain-related metrics., Discussion: This study reveals that the COMT Val158Met polymorphism results in genotype-specific functional changes in the brain's RS during menstrual pain. In Met carriers, engagement of these regions is potentially linked to motivational reward-seeking and top-down modulation. This polymorphism likely influences the RS's responses, significantly contributing to individual differences in pain regulation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Hsu, Liu, Yang, Lee, Li, Chao, Lin, Chen and Hsieh.)

Mitochondria are essential for energy supplementation and metabolic homeostasis of cancer cells. Using mitochondria transplantation to reduce the malignancy of gastric cancer (GC) cells is herein proposed. In our study normal human gastric mucous epithelium cell line (GES-1) showed a lower mitochondrial membrane potential (MMP) compared to immortalized human vascular endothelial cell line (EAhy 926) and human gastric adenocarcinoma cell line (AGS). The transplantation of GES-1 mitochondria to AGS were confirmed both by confocal microscopy and flow cytometry. After transplanting GES-1 mitochondria, the AGS showed a reduced cell migration, and invasion without affecting cell viability and apoptosis. Investigating the expression of proteins involved in epithelial-mesenchymal-transition (EMT), transplanted GES-1 mitochondria reduced the expression of mesenchymal markers α-SMA, MMP-9, snail, vimentin and N-cadherin, whereas the epithelial markers E-cadherin and clauding-1 were not changed. The proteins implicated in the cell cycle such as cyclin B1 and D1 were decreased. In mice, inoculation with AGS carrying the transplanted GES-1 mitochondria resulted in smaller sized tumors. Further investigating the mitochondrial balance, the transplanted GES-1 mitochondria were more stably preserved compared to endogenous AGS mitochondria. The MMP, ATP production and mitochondrial mass decreased in GES-1 mitochondria and the mitophagic proteins LC3 II and PINK1 were up-regulated. In conclusion the decreased malignancy of AGS was a result of exogenous GES-1 mitochondria transplantation. This suggests for a therapy with low efficiency mitochondria transplantation in the treatment of cancer cells., 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 B.V. and Mitochondria Research Society. All rights reserved.)

Antinuclear antibody (ANA) detection by indirect immunofluorescence (IIF) is instrumental in the evaluation of systemic autoimmune diseases (SADs). The dense fine speckled (DFS) ANA staining predominantly associates with anti-DFS70, an autoantibody that is thought to exclude the presence of SAD. However, the DFS pattern may mask the presence of other ANA patterns that may be clinically relevant. Our laboratory uses the HEp2010 substrate which contains both HEp2 and liver substates. The aim of this study was to determine whether negative liver nucleus immunofluorescence could exclude the presence of antibodies to extractable nuclear antigens (ENA) in sera with DFS-like patterns. One hundred consecutive sera samples suspicious for DFS pattern, along with 15 sera of control patterns (positive metaphase bars) were included in the study. Each sample was examined separately on HEp2010 (Euroimmun) and liver by two independent readers. Anti-DFS70 was assessed by line and chemiluminescent immunoassays. DFS-like sera were more likely to be liver nucleus-negative compared with control sera. Of the liver-negative sera, 61/64 (95.3%) were deemed anti-ENA negative. Using the liver substrate in the evaluation of anti-ENA had a sensitivity of 90.0% and a negative predictive value of 95.4%. In our cohort, concurrent evaluation of sera with the liver substrate helped rule out the presence of other anti-ENA. This technique may be a safeguard for DFS-like ANA patterns that may mask underlying anti-ENA on IIF., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Oligopulmonary metastases from primary liver tumors are typically treated surgically. We evaluated the clinical outcomes after lung metastasectomy in patients with pulmonary metastases from primary liver tumors. We retrospectively enrolled 147 consecutive patients with lung metastases from liver cancer who had undergone pulmonary metastasectomies at three medical centers between February 2007 and December 2020. All patients were pathologically confirmed to have lung metastases from liver cancer. Among the 147 patients, 110, 17, and 20 initially underwent surgical resection, radiofrequency ablation, and transcatheter arterial embolization, respectively. The 5-year overall survival (OS) in the study cohort was 22%. Univariate analysis revealed four factors associated with better OS: surgical resection as the initial primary liver tumor treatment ( p = 0.004), a disease-free interval exceeding 12 months after the initial liver surgery ( p = 0.036), a lower Model for End-Stage Liver Disease (MELD)-Na score (≤20) for liver cirrhosis ( p = 0.044), and the absence of local liver tumor recurrence at the time of pulmonary metastasectomy ( p = 0.004). Multivariate analysis demonstrated that surgical resection as the initial primary liver tumor treatment and lower MELD-Na scores significantly correlated with better OS. Our findings can assist thoracic surgeons in selecting suitable patients for surgery and predicting surgical outcomes.

In recent years, mounting evidence has highlighted a global decline in male semen quality, paralleling an increase in male infertility problems. Such developments in the male reproductive system are likely due to a range of environmental factors, which could negatively affect the outcomes of pregnancy, reproductive health, and the well-being of fetuses. Different environmental contaminants ultimately accumulate in riverbed sediments due to gravity, so these sediments are frequently considered hotspots for pollutants. Therefore, understanding the detrimental effects of river sediment pollution on human reproductive health is crucial. This study indicates male germ cells' high vulnerability to environmental contaminants. There is a strong positive correlation between the concentration of complex accumulated pollutants from human activities and the reproductive toxicity observed in human testicular embryonic cell lines NCCIT and NTERA-2. This toxicity is characterized by increased levels of reactive oxygen species, disruption of critical cellular functions, genotoxic impacts, and the induction of cell apoptosis. This research marks a significant step in providing in vitro evidence of the damaging effects of environmental pollutants on the human male germline., 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 B.V. All rights reserved.)

X-ray photoelectron spectroscopy, reflection-absorption infrared spectroscopy, and temperature-programmed reaction/desorption have been employed to investigate the reaction of CH3-CHCl-C(=O)Cl on Cu (100), with the aid of density functional theory (DFT) calculations. Experimentally, CH3-CH=C=O (methylketene) is found to be the product from the dechlorination of CH3-CHCl-C(=O)Cl on Cu(100) at 120 K. The CH3-CH=C=O generated on the surface would dimerize to form 2,4-dimethylcyclobutane-1,3-dione below 180 K. In agreement with the experimental findings, our DFT molecular dynamics simulations demonstrate that the dechlorination of CH3-CHCl-C(=O)Cl, resulting in CH3-CH=C=O and two Cl atoms, occurs readily, completing within 0.6 ps at 300 K. The simulations also indicate that the cleavage of the CH-Cl bond precedes that of the C(=O)-Cl bond. The static DFT calculations suggest that the dimerization of CH3-CH=C=O primarily occurs through the coupling of two C=C bonds, which has a lower barrier of 38.08 kJ mol-1 compared to the 69.05 kJ mol-1 barrier for C=C + C=O coupling., (© 2024 Author(s). Published under an exclusive license by AIP Publishing.)

Background: Whether myomectomy increases the risk of placenta accreta spectrum in the following pregnancies remains controversial., Objective: This study aimed to investigate the effect of myomectomy on the risk of placenta accreta spectrum in the following pregnancies. Moreover, different methods of myomectomy on the risk of placenta accreta spectrum were explored., Study Design: A nationwide cohort study was conducted using data from the Taiwan National Health Insurance Research Database, including all pregnant patients in Taiwan who gave birth between January 2008 and December 2017. A 1:1 propensity score estimation matching was performed for the analysis of myomectomy on the risk of placenta accreta spectrum. Among pregnant patients who received myomectomy, different methods of myomectomy on the risk of placenta accreta spectrum were compared with the control group., Results: Among the 1,371,458 pregnant patients in this study, 11,255 pregnant patients had a history of myomectomy. The risk of placenta accreta spectrum was higher in pregnant patients with a history of myomectomy than in pregnant patients without a history of myomectomy (incidence: 0.96% vs 0.20%; adjusted odds ratio, 2.28; 95% confidence interval, 1.85-2.81; P<.01). Among pregnant patients with a history of myomectomy, 5045 (46.87%) received laparotomic myomectomy, 3973 (36.93%) received laparoscopic myomectomy, and 1742 (16.20%) received hysteroscopic myomectomy. The incidence of placenta accreta spectrum was higher in the hysteroscopic group than in the laparotomic group or the laparoscopic group (1.89% [hysteroscopic group] vs 0.71% [laparotomic group] and 0.81% [laparoscopic group]; P<.05). Compared with patients without a history of myomectomy, the adjusted odds ratio for placenta accreta spectrum was 3.88 (95% confidence interval, 2.68-5.63; P<.05) in the hysteroscopic group., Conclusion: Myomectomy, especially hysteroscopic myomectomy, is associated with an increased risk of placenta accreta spectrum in the subsequent pregnancy., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Study Objective: This study aimed to compare the analgesic effects of anesthesiologist-administrated erector spinae plane block (ESPB) and surgeon-administrated intercostal nerve block (ICNB) following video-assisted thoracoscopic surgery (VATS)., Design: Randomized, controlled, double-blinded study., Setting: Operating room, postoperative recovery room and ward in two centers., Patients: One hundred patients, ASA I-III and scheduled for elective VATS., Interventions: The anesthesiologist-administrated ESPB under ultrasound guidance or surgeon-administrated ICNB under video-assisted thoracoscopy was randomly provided during VATS. Regular oral non-opioid analgesic combined with intravenous rescue morphine were prescribed for multimodal analgesia after surgery., Measurements: The primary outcomes were the pain score and morphine consumption during 48 h after surgery. Postoperative pain intensity were assessed using the 10-cm visual analogue scale at 1 h, 24 h, and 48 h after surgery. Morphine consumption at these time points was compared between the two study groups. Furthermore, oral weak opioid rescue analgesic was also provided at 24 h after surgery. Postoperative quality of recovery at 24 h was also assessed using the QoR-15 questionnaire, along with duration of chest tube drainage and hospital stay were compared as secondary outcomes., Main Results: Patients in the two study groups had comparable baseline characteristics, and surgical types were also similar. Postoperative VAS changes at 1 h, 24 h, and 48 h after surgery were also comparable between the two study groups. Both groups had low median scores (<4.0) at all time points (all p > 0.05). Patients in the ESPB group required statistically non-significant higher 48-h morphine consumption [3 (0-6) vs. 0 (0-6) mg in the ESPB group and ICNB group respectively; p = 0.135] and lower numbers of oral rescue analgesic (0.4 ± 1.2 vs. 1.0 ± 1.8 in the ESPB group and ICNB group respectively; p = 0.059). Additionally, patients in the two study groups had similar QoR15 scores and lengths of hospital stay., Conclusions: Both anesthesiologist-administered ultrasound-guided ESPB and surgeon-administered VATS ICNB were effective analgesic techniques for patients undergoing VATS for tumor resection., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Anti-IgLON5 (IgLON5-IgG)-associated disease is a newly defined clinical entity. This literature review aims to evaluate its pathogenesis, which remains a pivotal question. Features that favour a primary neurodegenerative mechanism include the non-inflammatory tauopathy neuropathological signature and overrepresentation of microtubule-associated protein tau ( MAPT ) H1/H1 genotype as seen in other sporadic tauopathies. In contrast, the cell-surface localisation of IgLON5, capability of anti-IgLON5 antibodies to exert direct in vitro pathogenicity and disrupt IgLON5 interactions with its binding partners, human leukocyte antigen (HLA)-DRB1*10:01 and HLA-DQB1*05:01 allele preponderance with high affinity binding of IgLON5 peptides, and responsiveness to immunotherapy favour a primary autoimmune process. The presentation and course of anti-IgLON5-associated disease is heterogenous; hence, we hypothesise that a multitude of immune mechanisms are likely simultaneously operational in this disease cohort.

Sublobar resection has emerged as a standard treatment option for early-stage peripheral non-small cell lung cancer. Achieving an adequate resection margin is crucial to prevent local tumor recurrence. However, gross measurement of the resection margin may lack accuracy due to the elasticity of lung tissue and interobserver variability. Therefore, this study aimed to develop an objective measurement method, the CT-based 3D reconstruction algorithm, to quantify the resection margin following sublobar resection in lung cancer patients through pre- and post-operative CT image comparison. An automated subvascular matching technique was first developed to ensure accuracy and reproducibility in the matching process. Following the extraction of matched feature points, another key technique involves calculating the displacement field within the image. This is particularly important for mapping discontinuous deformation fields around the surgical resection area. A transformation based on thin-plate spline is used for medical image registration. Upon completing the final step of image registration, the distance at the resection margin was measured. After developing the CT-based 3D reconstruction algorithm, we included 12 cases for resection margin distance measurement, comprising 4 right middle lobectomies, 6 segmentectomies, and 2 wedge resections. The outcomes obtained with our method revealed that the target registration error for all cases was less than 2.5 mm. Our method demonstrated the feasibility of measuring the resection margin following sublobar resection in lung cancer patients through pre- and post-operative CT image comparison. Further validation with a multicenter, large cohort, and analysis of clinical outcome correlation is necessary in future studies.

Introduction: To utilize machine learning techniques to develop an association model linking lung cancer and environmental hormones to enhance the understanding of potential lung cancer risk factors and refine current nursing assessments for lung cancer., Design: This study is exploratory in nature. In Stage 1, data were sourced from a biological database, and machine learning methods, including logistic regression and neural-like networks, were employed to construct an association model. Results indicate significant associations between lung cancer and blood cadmium, urine cadmium, urine cadmium/creatinine, and di(2-ethylhexyl) phthalate. In Stage 2, 128 lung adenocarcinoma patients were recruited through convenience sampling, and the model was validated using a questionnaire assessing daily living habits and exposure to environmental hormones., Results: Analysis reveals correlations between the living habits of patients with lung adenocarcinoma and exposure to blood cadmium, urine cadmium, urine cadmium/creatinine, polyaromatic hydrocarbons, diethyl phthalate, and di(2-ethylhexyl) phthalate., Conclusions: According to the World Health Organization's global statistics, lung cancer claims approximately 1.8 million lives annually, with more than 50% of patients having no history of smoking or non-traditional risk factors. Environmental hormones have garnered significant attention in recent years in pathogen exploration. However, current nursing assessments for lung cancer risk have not incorporated environmental hormone-related factors. This study proposes reconstructing existing lung cancer nursing assessments with a comprehensive evaluation of lung cancer risks., Clinical Relevance: The findings underscore the importance of future studies advocating for public screening of environmental hormone toxins to increase the sample size and validate the model externally. The developed association model lays the groundwork for advancing cancer risk nursing assessments., (© 2024 The Author(s). Journal of Nursing Scholarship published by Wiley Periodicals LLC on behalf of Sigma Theta Tau International.)

The presence of spread through air spaces (STASs) in early-stage lung adenocarcinoma is a significant prognostic factor associated with disease recurrence and poor outcomes. Although current STAS detection methods rely on pathological examinations, the advent of artificial intelligence (AI) offers opportunities for automated histopathological image analysis. This study developed a deep learning (DL) model for STAS prediction and investigated the correlation between the prediction results and patient outcomes. To develop the DL-based STAS prediction model, 1053 digital pathology whole-slide images (WSIs) from the competition dataset were enrolled in the training set, and 227 WSIs from the National Taiwan University Hospital were enrolled for external validation. A YOLOv5-based framework comprising preprocessing, candidate detection, false-positive reduction, and patient-based prediction was proposed for STAS prediction. The model achieved an area under the curve (AUC) of 0.83 in predicting STAS presence, with 72% accuracy, 81% sensitivity, and 63% specificity. Additionally, the DL model demonstrated a prognostic value in disease-free survival compared to that of pathological evaluation. These findings suggest that DL-based STAS prediction could serve as an adjunctive screening tool and facilitate clinical decision-making in patients with early-stage lung adenocarcinoma.

This study established and investigated continuous macular pigment (MP) production with a lutein (L):zeaxanthin (Z) ratio of 4-5:1 by an MP-rich Chlorella sp. CN6 mutant strain in a continuous microalgal culture module. Chlorella sp. CN6 was cultured in a four-stage module for 10 days. The microalgal culture volume increased to 200 L in the first stage (6 days). Biomass productivity increased to 0.931 g/L/day with continuous indoor white light irradiation during the second stage (3 days). MP content effectively increased to 8.29 mg/g upon continuous, indoor white light and blue light-emitting diode irradiation in the third stage (1 day), and the microalgal biomass and MP concentrations were 8.88 g/L and 73.6 mg/L in the fourth stage, respectively. Using a two-step MP extraction process, 80 % of the MP was recovered with a high purity of 93 %, and its L:Z ratio was 4-5:1., 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 Ltd. All rights reserved.)

Background: Despite the significant impact of chemotherapy-induced peripheral neuropathy on the quality of life for breast cancer survivors, there is a notable lack of comprehensive research. Therefore, a crucial need exists for further systematic investigation and inquiry into this matter., Aims: This study examined predictors of quality of life in breast cancer survivors with chemotherapy-induced peripheral neuropathy., Design: A cross-sectional, correlational design., Settings: This study was conducted at a medical center in northern Taiwan and a teaching hospital in northeastern Taiwan., Participants/subjects: One hundred and thirty adult women with breast cancer, who have undergone chemotherapy and obtained a Total Neuropathy Scale-Clinical Version score>0, were enrolled., Methods: Neuropathic pain, sleep disturbances, depression, and quality of life were evaluated using multiple regression analysis to identify quality of life predictors. Clinical importance was established using the minimally important difference of Functional Assessment of Cancer Therapy-Breast., Results: The study indicated that improving depression (B = -10.87, p < .001) and neuropathic pain (B = -8.33, p = .004) may enhance the quality of life of breast cancer survivors with chemotherapy-induced peripheral neuropathy. Moreover, the individual's marital status and family history of breast cancer were identified as predictive factors., Conclusions: This study illuminates quality of life determinants for breast cancer survivors with chemotherapy-induced peripheral neuropathy, advocating comprehensive care and addressing depression and neuropathic pain for better outcomes., Competing Interests: Declaration of competing interest All authors declare no conflicts of interest., (Copyright © 2024 American Society for Pain Management Nursing. Published by Elsevier Inc. All rights reserved.)

Deficiency of Adenosine Deaminase 2 (DADA2) patients presenting with primary immunodeficiency are at risk of uncontrolled EBV infection and secondary malignancies including EBV-related lymphoproliferative disorders (LPD). This paper describes the first case of EBV related diffuse large B-cell lymphoma in a patient with DADA2 and uncontrolled EBV infection. Consideration should be given to monitoring for EBV viraemia and to preventative EBV specific therapy in DADA2 and patients with at risk primary immunodeficiencies. A type I interferon (IFN) gene signature is associated with DADA2 though its association with immune dysregulation is unclear., (© 2024. The Author(s).)

Lithium-ion batteries, with high energy density and long cycle life, have become the battery of choice for most vehicles and portable electronic devices; however, energy density, safety and cycle life require further improvements. Single-functional group electrolyte additives are very limited in practical applications, a ternary polymer bifunctional electrolyte additive copolymer (acrylonitrile-butyl hexafluoro methacrylate- poly (ethylene glycol) methacrylate- methyl ether) (PMANHF) was synthesized by free radical polymerization of acrylonitrile, 2, 2, 3, 4, 4, 4-hexafluorobutyl methacrylate and poly (ethylene glycol) methyl ether methacrylate. A series of characterizations show that in Li metal anodes, the preferential reduction of PMANHF is conducive to the formation of a uniform and stable solid electrolyte interphase layer, and Li deposition is uniform and dense. At the NCM811 cathode, a film composed of LiF- and Li 3 N-rich is formed at the cathode-electrolyte interface, mitigating the side reaction at the interface. At 1.0 mA cm -2 , the Li/Li cell can be stabilized for 1000 cycles. In addition, the Li/NCM811 cell can stabilize 200 cycles with a cathode capacity of 153.7 mAh g -1 , with the capacity retention of 89.93 %, at a negative/positive capacity ratio of 2.5. This study brings to light essential ideas for the fabrication of additives for lithium-metal batteries., (© 2024 Wiley-VCH GmbH.)

Objectives: With the increasing popularity of CT screening, more cases of early-stage lung cancer are being diagnosed. However, 24.5% of stage I non-small-cell lung cancer (NSCLC) patients still experience treatment failure post-surgery. Biomarkers to predict lung cancer patients at high risk of recurrence are needed., Materials and Methods: We collected protein mass spectrometry data from the Taiwan Lung Cancer Moonshot Project and performed bioinformatics analysis on proteins with differential expressions between tumor and adjacent normal tissues in 74 stage I lung adenocarcinoma (LUAD) cases, aiming to explore the tumor microenvironment related prognostic biomarkers. Findings were further validated in 6 external cohorts., Results: The analysis of differentially expressed proteins revealed that the most enriched categories of diseases and biological functions were cellular movement, immune cell trafficking, and cancer. Utilizing proteomic profiling of the tumor microenvironment, we identified five prognostic biomarkers (ADAM10, MIF, TEK, THBS2, MAOA). We then developed a risk score model, which independently predicted recurrence-free survival and overall survival in stage I LUAD. Patients with high risk scores experienced worse recurrence-free survival (adjusted hazard ratio = 8.28, p < 0.001) and overall survival (adjusted hazard ratio = 6.88, p = 0.013). Findings had been also validated in the external cohorts., Conclusion: The risk score model derived from proteomic profiling of tumor microenvironment can be used to predict recurrence risk and prognosis of stage I LUAD., 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 B.V. All rights reserved.)

Objectives: Invasive adenocarcinomas (IADs) have been identified among nonsolid nodules (NSNs) assigned as Lung Imaging Reporting and Data System (Lung-RADS) category 2. This study used visual assessment for differentiating IADs from noninvasive lesions (NILs) in this category., Methods: This retrospective study included 222 patients with 242 NSNs, which were resected after preoperative computed tomography (CT)-guided dye localization. Visual assessment was performed by using the lung and bone window (BW) settings to classify NSNs into BW-visible (BWV) and BW-invisible (BWI) NSNs. In addition, nodule size, shape, border, CT attenuation, and location were evaluated and correlated with histopathological results. Logistic regression was performed for multivariate analysis. A p value of < 0.05 was considered statistically significant., Results: A total of 242 NSNs (mean diameter, 7.6 ± 2.8 mm), including 166 (68.6%) BWV and 76 (31.4%) BWI NSNs, were included. IADs accounted for 31% (75) of the nodules. Only 4 (5.3%) IADs were identified in the BWI group and belonged to the lepidic-predominant (n = 3) and acinar-predominant (n = 1) subtypes. In univariate analysis for differentiating IADs from NILs, the nodule size, shape, CT attenuation, and visual classification exhibited statistical significance. Nodule size and visual classification were the significant predictors for IAD in multivariate analysis with logistic regression (p < 0.05). The sensitivity, specificity, positive predictive value, and negative predictive value of visual classification in IAD prediction were 94.7%, 43.1%, 42.8%, and 94.7%, respectively., Conclusions: The window-based visual classification of NSNs is a simple and objective method to discriminate IADs from NILs., Clinical Relevance Statement: The present study shows that using the bone window to classify nonsolid nodules helps discriminate invasive adenocarcinoma from noninvasive lesions., Key Points: • Evidence has shown the presence of lung adenocarcinoma in Lung-RADS category 2 nonsolid nodules. • Nonsolid nodules are classified into the bone window-visible and the bone window-invisible nonsolid nodules, and this classification differentiates invasive adenocarcinoma from noninvasive lesions. • The Lung-RADS category 2 nonsolid nodules are unlikely invasive adenocarcinoma if they show nonvisualization in the bone window., (© 2023. The Author(s), under exclusive licence to European Society of Radiology.)

Background: In patients with advanced soft tissue sarcoma (STS), surgery had been reported to be associated with superior overall survival (OS). Chemotherapy details for such patients were less reported, and whether multimodal treatment with surgery and chemotherapy provides extra survival benefit remains unclear., Methods: We retrospectively reviewed patients with newly diagnosed advanced STS treated at National Taiwan University Hospital from January 1, 2011, to December 31, 2017. OS was calculated from the day of diagnosis of advanced STS to the day of death or last follow-up. Baseline patient characteristics and details regarding surgery and chemotherapy were recorded., Results: A total of 545 patients were diagnosed with STS from 2011 to 2017, of which 226 patients had advanced STS. The median age was 54.7 years, and 54% of patients were women. Approximately 38% of patients with advanced STS underwent surgery and exhibited a trend of longer OS compared with who did not (median = 18.6 vs. 11.9 months, p = 0.083). In the chemotherapy subgroup, the benefit of surgery was more prominent (median = 21.9 vs. 16.5 months, p = 0.037). Patients who received chemotherapy prior to surgery exhibited numerically longer OS than those who underwent surgery first (median = 33.9 vs. 18.3 months, p = 0.155). After adjusting other clinical factors, chemotherapy remained an independent factor associated with favourable OS., Conclusion: Surgery may be more beneficial for the patients who receive chemotherapy. Our results support evaluation of sequential multimodal treatments strategy including surgery and chemotherapy in patients with advanced STS., Competing Interests: Declaration of competing interest The authors declare no competing interests in this manuscript., (Copyright © 2024 Formosan Medical Association. Published by Elsevier B.V. All rights reserved.)

Blocking the interaction between the SARS-CoV-2 spike protein and the human angiotensin-converting enzyme II (hACE2) protein serves as a therapeutic strategy for treating COVID-19. Traditional Chinese medicine (TCM) treatments containing bioactive products could alleviate the symptoms of severe COVID-19. However, the emergence of SARS-CoV-2 variants has complicated the process of developing broad-spectrum drugs. As such, the aim of this study was to explore the efficacy of TCM treatments against SARS-CoV-2 variants through targeting the interaction of the viral spike protein with the hACE2 receptor. Antiviral activity was systematically evaluated using a pseudovirus system. Scutellaria baicalensis ( S. baicalensis ) was found to be effective against SARS-CoV-2 infection, as it mediated the interaction between the viral spike protein and the hACE2 protein. Moreover, the active molecules of S. baicalensis were identified and analyzed. Baicalein and baicalin, a flavone and a flavone glycoside found in S. baicalensis , respectively, exhibited strong inhibitory activities targeting the viral spike protein and the hACE2 protein, respectively. Under optimized conditions, virus infection was inhibited by 98% via baicalein-treated pseudovirus and baicalin-treated hACE2. In summary, we identified the potential SARS-CoV-2 inhibitors from S. baicalensis that mediate the interaction between the Omicron spike protein and the hACE2 receptor. Future studies on the therapeutic application of baicalein and baicalin against SARS-CoV-2 variants are needed.

Background: Sublobar resection is strongly associated with poor prognosis in early-stage lung adenocarcinoma, with the presence of tumor spread through air spaces (STAS). Thus, preoperative prediction of STAS is important for surgical planning. This study aimed to develop a STAS deep-learning (STAS-DL) prediction model in lung adenocarcinoma with tumor smaller than 3 cm and a consolidation-to-tumor (C/T) ratio less than 0.5., Methods: The study retrospectively enrolled of 581 patients from two institutions between 2015 and 2019. The STAS-DL model was developed to extract the feature of solid components through solid components gated (SCG) for predicting STAS. The STAS-DL model was assessed with external validation in the testing sets and compared with the deep-learning model without SCG (STAS-DL woSCG ), the radiomics-based model, the C/T ratio, and five thoracic surgeons. The performance of the models was evaluated using area under the curve (AUC), accuracy and standardized net benefit of the decision curve analysis., Results: The study evaluated 458 patients (institute 1) in the training set and 123 patients (institute 2) in the testing set. The proposed STAS-DL yielded the best performance compared with the other methods in the testing set, with an AUC of 0.82 and an accuracy of 74%, outperformed the STAS-DL woSCG with an accuracy of 70%, and was superior to the physicians with an AUC of 0.68. Moreover, STAS-DL achieved the highest standardized net benefit compared with the other methods., Conclusion: The proposed STAS-DL model has great potential for the preoperative prediction of STAS and may support decision-making for surgical planning in early-stage, ground glass-predominant lung adenocarcinoma., (© 2023. Society of Surgical Oncology.)

Aims: Advanced maternal age (AMA) is correlated with higher risk of adverse pregnancy outcomes while the pathophysiology remains unclear. Our study aimed to investigate whether AMA is linked to the clustering of metabolic abnormalities, which in turn is associated with an increased risk of adverse pregnancy outcomes., Method: A total of 857 pregnant woman were recruited in a prospective cohort at National Taiwan University Hospital, from November 2013 to April 2018. Metabolic abnormalities during pregnancy were defined as following: fasting plasma glucose ≥92 mg/dl, body mass index (BMI) ≥24 kg/m 2 , plasma high-density lipoprotein cholesterol <50 mg/dl, hyper-triglyceridemia (≥140 mg/dl in the first trimester or ≥220 mg/dl in the second trimester), and blood pressure ≥130/85 mmHg., Result: Incidence of large for gestational age (LGA), primary caesarean section (CS), and the presence of any adverse pregnancy outcome increased with age. The advanced-age group tended to have more metabolic abnormalities in both the first and the second trimesters. There was a significant association between the number of metabolic abnormalities in the first and the second trimesters and the incidence of LGA, gestational hypertension or preeclampsia, primary CS, preterm birth, and the presence of any adverse pregnancy outcome, adjusted for maternal age., Conclusion: AMA is associated with clustering of metabolic abnormalities during pregnancy, and clustering of metabolic abnormalities is correlated with increased risk of adverse pregnancy outcomes., Competing Interests: Declaration of competing interest The authors declared no conflict of interest., (Copyright © 2024 Formosan Medical Association. Published by Elsevier B.V. All rights reserved.)

Objectives: Primary spontaneous pneumothorax (PSP) is a common disease in young and thin male. Operation has been regarded as definitive treatment for it. However, the operative methods for those patients are under dispute. This study aims to directly compare the outcomes of uniportal VATS vs. needlescopic VATS in the treatment of PSP, focusing on postoperative pain and safety outcomes., Methods: From July 2013 to December 2017, the patients who underwent video-assisted thoracic surgery for pneumothorax in National Taiwan University Hospital were retrospectively collected. The preoperative condition, surgical results, and postoperative outcomes was analyzed., Results: There were 60 patients undergoing needlescopic VATS and 91 undergoing uniportal VATS during the study period. There was no significant difference between the patients who underwent needlescopic VATS and those who underwent uniportal VATS in their demographic and clinical characteristics. The post-operative pain score was significantly lower in the uniportal VATS group compared to the needlescopic VATS group at day 1 (2.65 ± 1.59 vs. 1.74 ± 1.35, p  = 0.001)., Conclusion: Uniportal VATS offers an effective, safe alternative for PSP treatment, with benefits including reduced post-operative pain. Our findings support the use of uniportal VATS, supplemented by a wound protector, as a viable option for PSP patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Chuang, Hsu, Lin, Huang, Kuo, Chen and Chen.)

Gynecologic tract melanoma is a malignant tumor with poor prognosis. Because of the low survival rate and the lack of a standard treatment protocol related to this condition, the investigation of the mechanisms underlying melanoma progression is crucial to achieve advancements in the relevant gynecological surgery and treatment. Mitochondrial transfer between adjacent cells in the tumor microenvironment regulates tumor progression. This study investigated the effects of endothelial mitochondria on the growth of melanoma cells and the activation of specific signal transduction pathways following mitochondrial transplantation. Mitochondria were isolated from endothelial cells (ECs) and transplanted into B16F10 melanoma cells, resulting in the upregulation of proteins associated with tumor growth. Furthermore, enhanced antioxidation and mitochondrial homeostasis mediated by the Sirt1-PGC-1α-Nrf2-HO-1 pathway were observed, along with the inhibition of apoptotic protein caspase-3. Finally, the transplantation of endothelial mitochondria into B16F10 cells promoted tumor growth and increased M2-type macrophages through Nrf2/HO-1-mediated pathways in a xenograft animal model. In summary, the introduction of exogenous mitochondria from ECs into melanoma cells promoted tumor growth, indicating the role of mitochondrial transfer by stromal cells in modulating a tumor's phenotype. These results provide valuable insights into the role of mitochondrial transfer and provide potential targets for gynecological melanoma treatment.

Background: Large-for-gestational-age (LGA) neonates have increased risk of adverse pregnancy outcomes and adult metabolic diseases. We aimed to investigate the relationship between plasma angiopoietin-like protein 4 (ANGPTL4), a protein involved in lipid and glucose metabolism during pregnancy, placental function, growth factors, and the risk of LGA., Methods: We conducted a prospective cohort study and recruited women with singleton pregnancies at the National Taiwan University Hospital between 2013 and 2018. First trimester maternal plasma ANGPTL4 concentrations were measured., Results: Among 353 pregnant women recruited, the LGA group had higher first trimester plasma ANGPTL4 concentrations than the appropriate-for-gestational-age group. Plasma ANGPTL4 was associated with hemoglobin A1c, post-load plasma glucose, plasma triglyceride, plasma free fatty acid concentrations, plasma growth hormone variant (GH-V), and birth weight, but was not associated with cord blood growth factors. After adjusting for age, body mass index, hemoglobin A1c, and plasma triglyceride concentrations, plasma ANGPTL4 concentrations were significantly associated with LGA risk, and its predictive performance, as measured by the area under the receiver operating characteristic curve, outperformed traditional risk factors for LGA., Conclusions: Plasma ANGPTL4 is associated with glucose and lipid metabolism during pregnancy, plasma GH-V, and birth weight, and is an early biomarker for predicting the risk of LGA., 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 B.V. All rights reserved.)

Objective: Small-for-gestational-age (SGA) neonates are at increased risk of perinatal mortality and morbidity. We aimed to investigate the performance of uterine artery pulsatility index (UtA-PI) at 19-24 weeks' gestation to predict the delivery of a SGA neonate in a Chinese population., Methods: This was a retrospective cohort study using data obtained between January 2010 and June 2018. Doppler ultrasonography was performed at 19-24 weeks' gestation. SGA was defined as birth weight below the 10 th centile according to the INTERGROWTH-21 st fetal growth standards. The performance of UtA-PI to predict the delivery of a SGA neonate was assessed using receiver-operating-characteristics (ROC)-curve analysis., Results: We included 6964 singleton pregnancies, of which 748 (11%) delivered a SGA neonate, including 115 (15%) women with preterm delivery. Increased UtA-PI was associated with an elevated risk of SGA, both in neonates delivered at or after 37 weeks' gestation (term SGA) and those delivered before 37 weeks (preterm SGA). The areas under the ROC curve (AUCs) for UtA-PI were 64.4% (95% CI, 61.5-67.3%) and 75.8% (95% CI, 69.3-82.3%) for term and preterm SGA, respectively. The performance of combined screening by maternal demographic/clinical characteristics and estimated fetal weight in the detection of term and preterm SGA was improved significantly by the addition of UtA-PI, although the increase in AUC was modest (2.4% for term SGA and 4.9% for preterm SGA)., Conclusions: This is the first Chinese study to evaluate the role of UtA-PI at 19-24 weeks' gestation in the prediction of the delivery of a neonate with SGA. The addition of UtA-PI to traditional risk factors improved the screening performance for SGA, and this improvement was greater in predicting preterm SGA compared with term SGA. © 2023 International Society of Ultrasound in Obstetrics and Gynecology., (© 2023 International Society of Ultrasound in Obstetrics and Gynecology.)

Glutathione (GSH) is a major antioxidant in organisms. An alteration in GSH concentration has been implicated in a number of pathological conditions. Therefore, GSH sensing has become a critical issue. In this study, a disposable strip used for tyrosinase-modified electrochemical testing was fabricated for the detection of GSH levels in vivo . The system is based on tyrosinase as a biorecognition element and a screen-printed carbon electrode (SPCE) as an amperometric transducer. On the tyrosinase-SPCE strips, the oxidation reaction from catechol to o -quinone was catalyzed by tyrosinase. The tyrosinase-SPCE strips were modified with gold nanoparticles (AuNPs). In the presence of AuNPs of 25 nm diameter, the cathodic peak current of cyclic voltammetry (CV) was significantly enhanced by 5.2 fold. Under optimized conditions (250 μM catechol, 50 mM phosphate buffer, and pH 6.5), the linear response of the tyrosinase-SPCE strips ranged from 31.25 to 500 μM GSH, with a detection limit of approximately 35 μM (S/N > 3). The tyrosinase-SPCE strips have been used to detect real samples of plasma and tissue homogenates in a mouse experiment. The mice were orally administrated with N -acetylcysteine (NAC) 100 mg kg -1 once a day for 7 days; the plasma GSH significantly enhanced 2.8 fold as compared with saline-treated mice (1123 vs. 480 μM μg -1 protein). NAC administration also could alleviate the adverse effect of GSH reduction in the mice treated with doxorubicin., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)