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Recently, hydrogen (H2) energy has attracted attention among eco-friendly energy sources because H2 energy is eco-friendly, energy-efficient, and abundant in nature. However, when the concentration of H2 in the atmosphere is more than 4%, H2 has a risk of explosion. H2 is a colorless, tasteless, and odorless gas that is difficult to detect with human senses. Therefore, developing an optimized hydrogen sensor is essential. Palladium (Pd) has good reactivity to hydrogen. Molybdenum disulfide (MoS2) has high carrier mobility, sensitive reactivity to toxic gases, and high surface-area-to-volume ratio. Therefore, we proposed hydrogen sensors that use Pd and MoS2. The main fabrication processes include MoS2 deposition through CVD and Pd deposition through DC sputtering. In this study, we utilized Pd and MoS2 to enable sensing at room temperature. By optimizing the Pd to a nanoparticle structure with an expansive surface area of 4 nm, we achieved a fast response time of 4–5 s and an enhanced yield through a simplified structure. Hydrogen sensors inherently exhibit sensitivity to various environmental factors. To address these challenges, technologies such as machine learning can be incorporated. Emphasizing low-power consumption and various application compatibilities becomes pivotal to promoting commercialization across diverse industries. [ABSTRACT FROM AUTHOR]

Hibiscus sabdariffa is a tropical plant with red calyxes whose anthocyanins, phenols, and antioxidant activity make it attractive to consumers both from a nutritional and medicinal standpoint. Its seasonality, perishability, and anthocyanin instability, led to the setup of stabilization methods comprising drying and powdering. However, its properties can often be altered during these stabilization processes. Treatments such as dehumidified-air-drying, infrared drying, and oven-drying, and their combination showed better quality preservation. Moreover, powder production enables superior biomolecule extractability which can be linked to a higher bioaccessibility. However, the required temperatures for powder production increase the bioactive molecules degradation leading to their antioxidant activity loss. To overcome this issue, ambient or cryogenic grinding could be an excellent method to improve the biomolecule bioavailability and accessibility if the processing steps are well mastered. To be sure to benefit from the final nutritional quality of the powder, such as the antioxidant activity of biomolecules, powders have to offer excellent reconstitutability which is linked to powder physicochemical properties and the reconstitution media. Typically, the finest powder granulometry and using an agitated low-temperature reconstitution media allow for improving anthocyanin extractability and stability. In this review, the relevant physicochemical and processing parameters influencing plant powder features from processing transformation to reconstitution will be presented with a focus on bioactive molecules and antioxidant activity preservation.

Abstract Background Plant systemic signaling characterized by the long distance transport of molecules across plant organs involves the xylem and phloem conduits. Root-microbe interactions generate systemic signals that are transported to aerial organs via the xylem sap. We analyzed the xylem sap proteome of soybean seedlings in response to pathogenic and symbiotic interactions to identify systemic signaling proteins and other differentially expressed proteins. Results We observed the increase of a serine protease and peroxidase in the xylem sap in response to Phytophthora sojae elicitor treatment. The high molecular weight fraction of soybean xylem sap was found to promote the growth of Neurospora crassa in vitro at lower concentrations and inhibit growth at higher concentrations. Sap from soybean plants treated with a P. sojae elicitor had a significantly higher inhibitory effect than sap from control soybean plants. When soybean seedlings were inoculated with the symbiont Bradyrhizobium japonicum, the abundance of a xyloglucan transendoglycosyl transferase protein increased in the xylem sap. However, RNAi-mediated silencing of the corresponding gene did not significantly affect nodulation in soybean hairy root composite plants. Conclusion Our study identified a number of sap proteins from soybean that are differentially induced in response to B. japonicum and P. sojae elicitor treatments and a majority of them were secreted proteins.

Treatment assessment and patient outcome for sepsis depend predominantly on the timely administration of appropriate antibiotics 1-3 . However, the clinical protocols used to stratify and select patient-specific optimal therapy are extremely slow 4 . In particular, the major hurdle in performing rapid antimicrobial susceptibility testing (AST) remains in the lengthy blood culture procedure, which has long been considered unavoidable due to the limited number of pathogens present in the patient's blood. Here we describe an ultra-rapid AST method that bypasses the need for traditional blood culture, thereby demonstrating potential to reduce the turnaround time of reporting drug susceptibility profiles by more than 40-60 h compared with hospital AST workflows. Introducing a synthetic beta-2-glycoprotein I peptide, a broad range of microbial pathogens are selectively recovered from whole blood, subjected to species identification or instantly proliferated and phenotypically evaluated for various drug conditions using a low-inoculum AST chip. The platform was clinically evaluated by the enrolment of 190 hospitalized patients suspected of having infection, achieving 100% match in species identification. Among the eight positive cases, six clinical isolates were retrospectively tested for AST showing an overall categorical agreement of 94.90% with an average theoretical turnaround time of 13 ± 2.53 h starting from initial blood processing., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: Apolipoprotein B mRNA editing catalytic polypeptide (APOBEC), an endogenous mutator, induces DNA damage and activates the ataxia telangiectasia and Rad3-related (ATR)-checkpoint kinase 1 (Chk1) pathway. Although cisplatin-based therapy is the mainstay for muscle-invasive bladder cancer (MIBC), it has a poor survival rate. Therefore, this study aimed to evaluate the efficacy of an ATR inhibitor combined with cisplatin in the treatment of APOBEC catalytic subunit 3B (APOBEC3B) expressing MIBC., Methods: Immunohistochemical staining was performed to analyze an association between APOBEC3B and ATR in patients with MIBC. The APOBEC3B expression in MIBC cell lines was assessed using real-time polymerase chain reaction and western blot analysis. Western blot analysis was performed to confirm differences in phosphorylated Chk1 (pChk1) expression according to the APOBEC3B expression. Cell viability and apoptosis analyses were performed to examine the anti-tumor activity of ATR inhibitors combined with cisplatin., Conclusion: There was a significant association between APOBEC3B and ATR expression in the tumor tissues obtained from patients with MIBC. Cells with higher APOBEC3B expression showed higher pChk1 expression than cells expressing low APOBEC3B levels. Combination treatment of ATR inhibitor and cisplatin inhibited cell growth in MIBC cells with a higher APOBEC3B expression. Compared to cisplatin single treatment, combination treatment induced more apoptotic cell death in the cells with higher APOBEC3B expression. Conclusion: Our study shows that APOBEC3B's higher expression status can enhance the sensitivity of MIBC to cisplatin upon ATR inhibition. This result provides new insight into appropriate patient selection for the effective application of ATR inhibitors in MIBC., Competing Interests: The authors declare that they have no conflict of interest to report regarding the present study., (© 2024 Kim et al.)

Ovarian cancer is a lethal gynecologic cancer mostly diagnosed in an advanced stage with an accumulation of ascites. Interleukin-6 (IL-6), a pro-inflammatory cytokine is highly elevated in malignant ascites and plays a pleiotropic role in cancer progression. Mitochondria are dynamic organelles that undergo fission and fusion in response to external stimuli and dysregulation in their dynamics has been implicated in cancer progression and metastasis. Here, we investigate the effect of IL-6 on mitochondrial dynamics in ovarian cancer cells (OVCs) and its impact on metastatic potential. Treatment with IL-6 on ovarian cancer cell lines (SKOV3 and PA-1) led to an elevation in the metastatic potential of OVCs. Interestingly, a positive association was observed between dynamin-related protein 1 (Drp1), a regulator of mitochondrial fission, and IL-6R in metastatic ovarian cancer tissues. Additionally, IL-6 treatment on OVCs was linked to the activation of Drp1, with a notable increase in the ratio of the inhibitory form p-Drp1(S637) to the active form p-Drp1(S616), indicating enhanced mitochondrial fission. Moreover, IL-6 treatment triggered the activation of ERK1/2, and inhibiting ERK1/2 mitigated IL-6-induced mitochondrial fission. Suppressing mitochondrial fission through siRNA transfection and a pharmacological inhibitor reduced the IL-6-induced migration and invasion of OVCs. This was further supported by 3D invasion assays using patient-derived spheroids. Altogether, our study suggests the role of mitochondrial fission in the metastatic potential of OVCs induced by IL-6. The inhibition of mitochondrial fission could be a potential therapeutic approach to suppress the metastasis of ovarian cancer., (© 2024 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

Ovarian cancer is a leading cause of death among gynecologic tumors, often detected at advanced stages. Metabolic reprogramming and increased lipid biosynthesis are key factors driving cancer cell growth. Stearoyl-CoA desaturase 1 (SCD1) is a crucial enzyme involved in de novo lipid synthesis, producing mono-unsaturated fatty acids (MUFAs). Here, we aimed to investigate the expression and significance of SCD1 in epithelial ovarian cancer (EOC). Comparative analysis of normal ovarian surface epithelial (NOSE) tissues and cell lines revealed elevated SCD1 expression in EOC tissues and cells. Inhibition of SCD1 significantly reduced the proliferation of EOC cells and patient-derived organoids and induced apoptotic cell death. Interestingly, SCD1 inhibition did not affect the viability of non-cancer cells, indicating selective cytotoxicity against EOC cells. SCD1 inhibition on EOC cells induced endoplasmic reticulum (ER) stress by activating the unfolded protein response (UPR) sensors and resulted in apoptosis. The addition of exogenous oleic acid, a product of SCD1, rescued EOC cells from ER stress-mediated apoptosis induced by SCD1 inhibition, underscoring the importance of lipid desaturation for cancer cell survival. Taken together, our findings suggest that the inhibition of SCD1 is a promising biomarker as well as a novel therapeutic target for ovarian cancer by regulating ER stress and inducing cancer cell apoptosis., (© 2024. The Author(s).)

Objective: Poly(ADP-ribose) polymerase (PARP) inhibitors are used for targeted therapy for ovarian cancer with homologous recombination deficiency (HRD). In this study, we aimed to develop a homologous recombination deficiency prediction model to predict the genomic integrity (GI) index of the SOPHiA DDM HRD Solution from the Oncomine Comprehensive Assay (OCA) Plus. We also tried to a find cut-off value of the genomic instability metric (GIM) of the OCA Plus that correlates with the GI index of the SOPHiA DDM HRD Solution., Methods: We included 87 cases with high-grade ovarian serous carcinoma from five tertiary referral hospitals in Republic of Korea. We developed an HRD prediction model to predict the GI index of the SOPHiA DDM HRD Solution. As predictor variables in the model, we used the HRD score, which included percent loss of heterozygosity (%LOH), percent telomeric allelic imbalance (%TAI), percent large-scale state transitions (%LST), and the genomic instability metric (GIM). To build the model, we employed a penalized logistic regression technique., Results: The final model equation is -21.77 + 0.200 × GIM + 0.102 × %LOH + 0.037 × %TAI + 0.261 × %LST. To improve the performance of the prediction model, we added a borderline result category to the GI results. The accuracy of our HRD status prediction model was 0.958 for the test set. The accuracy of HRD status using GIM with a cut-off value of 16 was 0.911., Conclusion: The Oncomine Comprehensive Assay Plus provides a reliable biomarker for homologous recombination deficiency., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Kang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Treatment challenges persist in advanced lung cancer despite the development of therapies beyond the traditional platinum-based chemotherapy. The early 2000s marked a shift to tyrosine kinase inhibitors targeting epidermal growth factor receptor, ushering in personalized genetic-based treatment. A further significant advance was the development of immune checkpoint inhibitors (ICIs), especially for non-small cell lung cancer. These target programmed death-ligand 1 (PD-L1) and cytotoxic T lymphocyte antigen 4, which enhanced the immune response against tumor cells. However, not all patients respond, and immune-related toxicities arise. This review emphasizes identifying biomarkers for ICI response prediction. While PD-L1 is a widely used, validated biomarker, its predictive accuracy is imperfect. Investigating tumor-infiltrating lymphocytes, tertiary lymphoid structure, and emerging biomarkers such as high endothelial venule, Human leukocyte antigen class I, T-cell immunoreceptors with Ig and ITIM domains, and lymphocyte activation gene-3 counts is promising. Understanding and exploring additional predictive biomarkers for ICI response are crucial for enhancing patient stratification and overall care in lung cancer treatment.

Well-differentiated papillary mesothelial tumor (WDPMT) is a distinct form of mesothelioma with low malignant potential and is mostly found in the peritoneal cavity. It consists of mesothelial cells with papillary structure and bland cytology. We report a rare case of WDPMT with suspicious invasive foci in the tunica vaginalis. WDPMT with invasive foci is known to have a tendency for recurrence. Therefore, careful attention should be given to properly diagnosing and treating this rare entity.

Analog in-memory computing synaptic devices are widely studied for efficient implementation of deep learning. However, synaptic devices based on resistive memory have difficulties implementing on-chip training due to the lack of means to control the amount of resistance change and large device variations. To overcome these shortcomings, silicon complementary metal-oxide semiconductor (Si-CMOS) and capacitor-based charge storage synapses are proposed, but it is difficult to obtain sufficient retention time due to Si-CMOS leakage currents, resulting in a deterioration of training accuracy. Here, a novel 6T1C synaptic device using only n-type indium gaIlium zinc oxide thin film transistor (IGZO TFT) with low leakage current and a capacitor is proposed, allowing not only linear and symmetric weight update but also sufficient retention time and parallel on-chip training operations. In addition, an efficient and realistic training algorithm to compensate for any remaining device non-idealities such as drifting references and long-term retention loss is proposed, demonstrating the importance of device-algorithm co-optimization., (© 2023 The Authors. Advanced Science published by Wiley-VCH GmbH.)

Background: The importance of molecular pathology tests has increased during the last decade, and there is a great need for efficient training of molecular pathology for pathology trainees and as continued medical education., Methods: The Molecular Pathology Study Group of the Korean Society of Pathologists appointed a task force composed of experienced molecular pathologists to develop a refined educational curriculum of molecular pathology. A 3-day online educational session was held based on the newly established structure of learning objectives; the audience were asked to score their understanding of 22 selected learning objectives before and after the session to assess the effect of structured education., Results: The structured objectives and goals of molecular pathology was established and posted as a web-based interface which can serve as a knowledge bank of molecular pathology. A total of 201 pathologists participated in the educational session. For all 22 learning objectives, the scores of self-reported understanding increased after educational session by 9.9 points on average (range, 6.6 to 17.0). The most effectively improved items were objectives from next-generation sequencing (NGS) section: 'NGS library preparation and quality control' (score increased from 51.8 to 68.8), 'NGS interpretation of variants and reference database' (score increased from 54.1 to 68.0), and 'whole genome, whole exome, and targeted gene sequencing' (score increased from 58.2 to 71.2). Qualitative responses regarding the adequacy of refined educational curriculum were collected, where favorable comments dominated., Conclusions: Approach toward the education of molecular pathology was refined, which would greatly benefit the future trainees.

Background: Factors involved in inflammation and cancer interact in various ways with each other, and biomarkers of systemic inflammation may have a prognostic value in cancer. Glucose transporter 1 (GLUT1) plays a pivotal role in glucose transport and metabolism and it is aberrantly expressed in various cancer types. We evaluated the differential expression of GLUT1, along with 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) in non-small-cell lung cancer (NSCLC), and then analyzed their prognostic significance., Methods: A total of 163 patients with resectable NSCLC were included in this study. Tumor sections were immunohistochemically stained for GLUT1 and GLUT3. Maximum standardized uptake value (SUV max ) was measured by preoperative FDG-PET, and neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), and lymphocyte-monocyte ratio (LMR) were derived from pretreatment blood count., Results: GLUT1 and GLUT3 was positively expressed in 74.8% and 6.1% of the NSCLC tissues, respectively. GLUT1 expression was significantly correlated with squamous cell carcinoma histology, poor differentiation, high pathologic stage, old age, male, smoking, and high SUV max (>7) (all p < 0.05). The squamous cell carcinoma and smoker group also showed significantly higher SUV max (both p < 0.001). Systemic inflammation markers, including NLR, PLR, and LMR, were positively correlated with high SUV max (all p < 0.05). High GLUT1 expression, high SUV max , high NLR, and low LMR, were significantly associated with poor overall survival in patients with NSCLC. However, in the multivariate survival analysis, LMR was an independent prognostic factor overall (HR 1.86, 95% CI 1.05-3.3) and for the stage I/II cohort (HR 2.3, 95% CI 1.24-4.3) (all p < 0.05)., Conclusions: Systemic inflammatory markers-NLR, PLR, and LMR are strongly correlated with the SUV max and are indicators of aggressive tumor behavior. Specifically, LMR is a promising prognostic biomarker in NSCLC patients.

Background: Although the Korean Society for Cytopathology has developed educational goals as guidelines for cytopathology education in Korea, there is still no systematic approach to cytopathology education status for pathology residents. Furthermore, satisfaction with cytopathology education and with the outcome of the current training/educational program has not been investigated in Korea. This study aimed to obtain comprehensive data on the current state of cytopathology education for residents and evaluate education outcomes., Methods: An online survey was conducted in December 2020 for the board-certified pathologists and training residents registered as members of the Korean Society for Cytopathology. The questionnaire comprised questions that investigated the current status of cytopathology at each training institution, the degree of satisfaction with the work and education related to cytopathology, outcomes of cytopathology training, and educational accomplishments., Results: Of the participants surveyed, 12.3% (132/1,075) completed the questionnaire, and 36.8% (32/87) of cytopathology residents participated. The mean overall satisfaction with cytopathology education was 3.1 points (on a 1- to 5-point scale, 5: very satisfied). The most frequent suggestion among the free description format responses was to expand educational opportunities, such as online education opportunities, outside of the individual institutions., Conclusions: Our results showed that cytopathology training in Korea needs further improvement. We expect that this study will inform systematic training of competent medical personnel armed with broad cytopathology knowledge and strong problem-solving abilities.

Massive retinal gliosis (MRG) is a rare condition of non-neoplastic glial proliferation, which forms massive lesions that fill the eye. MRG is commonly associated with phthisis bulbi (a non-functional eye), congenital anomalies, or malformations. Herein, we report a case of massive retinal gliosis associated with a traumatic phthisis bulbi, which was initially mistaken as a malignant intraocular tumor and confirmed only after an eye enucleation. A 70-year-old woman presented with a protruding ocular mass in her left eye which had slowly grown for a year. She had phthisis bulbi in her left eye due to trauma during her childhood. An orbital CT revealed an intraocular mass lesion with calcifications, raising the possibility of retinoblastoma or other malignant intraocular tumors. Enucleation of the left eye globe was performed. Histopathologic examination revealed exuberant proliferation of the glial cells, metaplastic bone formation, hyalinized vessels, and hyperplasia of the retinal pigment epithelium, confirming the diagnosis of MRG. Although rare, the possibility of MRG should be considered as a differential diagnosis when encountering an intraocular mass lesion, as it can be misdiagnosed as a malignant tumor.

Systemic mastocytosis is a neoplastic proliferation of mast cells that most frequently involves cutaneous sites. Mastocytosis involves various extracutaneous sites, but the lymph node is rare. We present an interesting image of systemic mastocytosis in the lymph node with marked eosinophilia. It is a rare subtype of systemic mastocytosis requiring high suspicion levels for the correct diagnosis.

Background: Synaptophysin is an immunohistochemical marker for neuroendocrine differentiation and is widely used in pathologic diagnosis. Its expression in malignant lymphoma has not yet been described. However, we experienced an index case of classic Hodgkin lymphoma with synaptophysin expression. This experience prompted us to investigate synaptophysin expression in classic Hodgkin lymphoma., Method: Immunohistochemical staining of synaptophysin was performed in 59 diagnosed cases of classic Hodgkin lymphoma, 10 anaplastic large cell lymphomas, 16 diffuse large B-cell lymphomas, and 5 extranodal marginal zone lymphoma of the mucosa-associated tissue. Synaptophysin-positive cases were stained for both chromogranin and CD56a., Result: Of 59 classic Hodgkin lymphoma cases, 11 (19%) were positive for synaptophysin. None of the anaplastic large cell lymphomas expressed synaptophysin. Synaptophysin showed weak but specific expression in the cytoplasm of the Hodgkin lymphoma tumor cells. Other background inflammatory cells (such as macrophages, B-, and T-lymphocytes) were all negative for synaptophysin expression. Chromogranin and CD56a were not expressed in the synaptophysin-positive classic Hodgkin lymphomas., Conclusions: Synaptophysin is an integral glycoprotein present in presynaptic vesicles of neurons and neuroendocrine cells. It is a diagnostic marker for neuroendocrine tumors. Aberrant synaptophysin expression has been reported in non-neuroendocrine tumors but not in lymphoma or leukemia. To the best of our knowledge, synaptophysin positivity has only been reported in a single case of precursor T-lymphoblastic leukemia/lymphoma to date. Our study showed that aberrant synaptophysin expression in classic Hodgkin lymphoma is an unexpectedly frequent finding. The mechanism underlying, and prognostic significance of, such aberrant expression is unclear. Thus, in a small biopsy, aberrant synaptophysin expression could be a diagnostic pitfall and should be carefully avoided., (© 2022. The Author(s).)

Background: The purpose of this study is to see if exfoliative pulmonary airway pathology in cancer-free coal workers' pneumoconiosis (CWP) can be used as a biomarker for predicting pulmonary morbidity., Methods: We investigated persistent metaplastic changes in bronchoscopic washing cytology and differential cell counts in bronchoalveolar lavages (BAL) in 97 miners with CWP and 80 miners without CWP as the control. Clinicopathological parameters were examined including pulmonary function tests and the presence of progressive massive fibrosis., Results: When compared to the control group, severe alveolitis, severe goblet cell hyperplasia (GCH), severe hyperplastic epithelial change, and severe squamous metaplasia were the distinguishing biomarkers in CWP. Multivariate analysis revealed that severe alveolitis and severe GCH, along with miner duration and current smoker, were independent predictors of pulmonary mortality. The survival analysis revealed a significantly different survival rate between the three groups: no evidence of severe alveolitis and severe GCH, presence of severe alveolitis or severe GCH but not both, and both severe alveolitis and severe GCH., Conclusions: The severities of alveolitis and goblet cell hyperplasia in the bronchoscopic study are independent prognostic factors for CWP. A pathologic grading system based on these two parameters could be used in the stratification and clinical management of CWP patients.

Background and Objectives: The prediction of the prognosis and effect of neoadjuvant therapy is vital for patients with advanced or unresectable colorectal carcinoma (CRC). Materials and Methods : We investigated several tumor microenvironment factors, such as intratumoral budding (ITB), desmoplastic reaction (DR), and Klintrup-Mäkinen (KM) inflammation grade, and the tumor-stroma ratio (TSR) in pretreatment biopsy samples (PBSs) collected from patients with advanced or unresectable CRC. A total of 85 patients with 74 rectal carcinomas and 11 colon cancers treated at our hospital were enrolled; 66 patients had curative surgery and 19 patients received palliative treatment. Results: High-grade ITB was associated with recurrence ( p = 0.002), death ( p = 0.034), and cancer-specific death ( p = 0.034). Immature DR was associated with a higher grade of clinical tumor-node-metastasis stage (cTNM) ( p = 0.045), cN category ( p = 0.045), and cM category ( p = 0.046). The KM grade and TSR were not related to any clinicopathological factors. High-grade ITB had a significant relationship with tumor regression in patients who received curative surgery ( p = 0.049). Conclusions: High-grade ITB in PBSs is a potential unfavorable prognostic factor for patients with advanced CRC. Immature DR, TSR, and KM grade could not predict prognosis or therapy response in PBSs.

A simple way to prepare field-effect transistors (FETs) using MoS 2 on tabletop is presented. Conductive silver paste was applied onto chemical vapor deposition (CVD)-grown MoS 2 as Ohmic-contact electrodes. Heating the device in vacuum further enhances the performance without damage. The final performance is comparable to that of the SiO 2 -backgated devices prepared by lithography and metal evaporators. The role of the silver paste and heat treatment in vacuum is investigated by device and spectroscopic analysis., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)

Background: A high platelet−lymphocyte ratio (PLR) is a marker of systemic inflammation and, together with the neutrophil−lymphocyte ratio (NLR), is associated with poor outcomes in several cancers. We investigated the prognostic value of PLR and other systemic inflammatory markers, such as NLR, systemic immune-inflammation index (SII), and systemic inflammation response index (SIRI), in oral squamous cell carcinoma (OSCC) patients undergoing surgical resection. Methods: We derived PLR, NLR, SII, and SIRI from a retrospective chart review of 269 consecutive OSCC patients. The complete blood count examined in the immediate preoperative period was used to compute PLR, NLR, SII, and SIRI. We analyzed the relationship between these systemic inflammatory markers and the clinicopathologic characteristics, disease-specific survival (DSS), and progression-free survival (PFS) of patients. Results: In the univariate analysis, high PLR and SII were significantly associated with worse DSS and PFS (all p < 0.05). In the multivariate analysis, PLR (HR 2.36, 95% CI 1.28−4.36 for DSS; HR 1.80, 95% CI 1.06−3.06 for PFS) was an independent predictor of survival outcomes. When PLR was analyzed as a continuous variable, the relationship between the outcome and preoperative PLR was not monotonically linear. In the subgroup analysis, PLR was more strongly associated with DSS and PFS in patients who were male, had stage III/IV OSCC, or had lymph node metastasis. Conclusion: Our data suggest that in OSCC patients, the pretreatment PLR is an independent predictor of DSS and PFS. The PLR is a readily available biomarker that will improve prognostication and risk stratification in OSCC.

The poor prognosis of ovarian cancer patients mainly results from a lack of early diagnosis approaches and a high rate of relapse. Only a very modest improvement has been made in ovarian cancer patient survival with traditional treatments. More targeted therapies precisely matching each patient are strongly needed. The aberrant activation of Wnt/β-catenin signaling pathway plays a fundamental role in cancer development and progression in various types of cancer including ovarian cancer. Recent insight into this pathway has revealed the potential of targeting Wnt/β-catenin in ovarian cancer treatment. This study aims to investigate the effect of CWP232291, a small molecular Wnt/β-catenin inhibitor on ovarian cancer progression. Various in vitro , in vivo and ex vivo models are established for CWP232291 testing. Results show that CWP232291 could significantly attenuate ovarian cancer growth through inhibition of β-catenin. Noticeably, CWP232291 could also s suppress the growth of cisplatin-resistant cell lines and ovarian cancer patient-derived organoids. Overall, this study has firstly demonstrated the anti-tumor effect of CWP232291 in ovarian cancer and proposed Wnt/β-catenin pathway inhibition as a novel therapeutic strategy against ovarian cancer., Competing Interests: Authors AY and C-LJ were employed by JW Pharmaceutical Corporation. The remaining 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. The authors declare that this study received funding from JW Pharmaceutical Corporation. The funder had the following involvement with the study: design and performance of the mouse experiment., (Copyright © 2022 Wang, Cho, Yoo, Jung, Kim, Kim, Lee, Jo, Han, Song, Lee, Kim, Lee, Ku, Lee and Song.)

Clamydophila psittaci ( C. psittaci ) has been proposed to be an etiologic factor in extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) in the ocular adnexa. However, the pathogenetical significance of the infection has not been fully elucidated. Many previous studies have shown controversial results regarding C. &nbsp; psittaci detection rates in said patients, ranging from 0 to 87%. We investigated the presence of C. psittaci in a single institutional cohort ( n = 150) of ocular adnexal MALT lymphoma (OAML) patients in Korea. We tried to exclude the methodological biases derived from the different primer sets in polymerase chain reaction-based studies. For that reason, we applied five sets of primers, including four previously reported and one newly designed primer set. There was no case of C. psittaci -positive OAML in repeated trials validated with appropriate positive and negative controls. All 150 cases showed negative results with five primer sets. These results suggest that the pathogenetic role of C. psittaci in ocular adnexal MALT lymphoma might have been overestimated to date, at least in the Korean population. Therefore, the molecular diagnosis of C. psittaci is considered a very low priority.

Objectives: Most diffuse gliomas are reported to harbor isocitrate dehydrogenase ( IDH ) mutations. However, when these mutations are tested in clinical practice, the results are often negative., Methods: This study examined the frequency of IDH1 and IDH2 mutations in gliomas classified according to the revised 2016 World Health Organization classification, and investigated their prognostic relevance. We tested 87 gliomas for IDH1 and IDH2 mutations using the peptide nucleic acid clamp method., Results: IDH1 mutations were observed in 42% of diffuse astrocytomas, 23% of anaplastic astrocytomas, all oligodendrogliomas and anaplastic oligodendrogliomas, and 17% of glioblastomas. An IDH2 mutation was identified in one case of diffuse astrocytoma. In the survival analysis of diffuse astrocytic tumors, patients with IDH1/2 -wildtype anaplastic astrocytomas tended to have a poor prognosis, similar to that of glioblastomas., Conclusions: IDH2 mutations were infrequent in gliomas. In anaplastic astrocytomas, the frequency of IDH1/2 -wildtype was relatively high, and the prognosis of patients with this type of tumor was very similar to that of those with glioblastomas. It may therefore be necessary to reconsider the classification and treatment strategies for IDH1/2 -wildtype anaplastic astrocytomas.

Diffuse large B-cell lymphoma (DLBCL) is the most common high-grade B-cell lymphoma found in Korea; it manifests with a variety of cellular morphologies and a high proliferation index. It is difficult to differentiate between DLBCL and Burkitt lymphoma (BL) based on immunohistochemistry, histology, and Epstein-Barr virus infection status owing to the overlap in findings. In this study, we performed comparative morphometric analysis to understand the proportional difference in Ki-67 staining between DLBCL and BL. We analyzed Ki-67-stained slides of 103 DLBCLs and 29 BLs that were pathologically confirmed using a three-tier classification system (negative, 1+, 2+, and 3+) to compare Ki-67 expression between BL and activated B-cell and germinal center B-cell subtypes of DLBCL and DLBCL with high proliferation indices (>90% of 2+ and 3+ cells). Patients with DLBCL were older than those with BL (62.1 versus 51.0 years). The number and proportion of negative cells (passenger and true negative cells) were significantly lower in BLs than those in DLBCLs (337.4, 5.9% versus 690.3, 12.4%). The number and proportion of 3+ cells were significantly higher in BLs than those in DLBCLs (5213.6, 96.3% versus 3132.4, 62.0%). BLs and DLBCLs with a high proliferation index showed similar results as those between BLs and overall DLBCLs. We were able to differentiate BLs and DLBCLs with 98.1% sensitivity and 100.0% specificity using an optimal cut-off of 97.9% of 2+/3+ Ki-67-positive cells. Thus, the Ki-67 labeling index may be a good differential biomarker for DLBCLs and BLs.

Development of acquired resistance to cisplatin (CDDP) is a major obstacle in the treatment of ovarian cancer patients. According to the cancer stem cell (CSC) hypothesis, the recurrence and chemoresistance are presumed to be linked to cancer stem/progenitor cells. Here, we investigated the CSC-like phenotypes and mechanism of chemoresistance in CDDP resistant ovarian cancer cells. A well-established CDDP sensitive ovarian cancer cell line A2780 and its resistant population A2780-Cp were used. We also developed a supra resistant population (SKOV3-Cp) from a naturally CDDP resistant cell line SKOV3. Both resistant/supra resistant cell lines showed significantly higher self-renewal capability than their parental counterparts. They also showed significant resistance to apoptosis and sub-G1 arrest by CDDP treatment. Stem cell marker ALDH1 positivity rates were higher both in A2780-Cp and SKOV3-Cp cell lines than in their counterparts, quantified by Aldefluor assay kit. Hoechst 33342 dye effluxing side populations were increased up to about five folds in A2780-Cp cells and two folds in SKOV3-Cp cells compared to A2780 and SKOV3 cells, respectively. Among major stemness related genes ( POU5F1 / OCT4, SOX2, NANOG, NES, BMI1, KLF4 and ALDH1A1 ), ALDH1A1 and KLF4 were significantly overexpressed in both resistant/supra resistant cells. Silencing ALDH1A1 in A2780 and A2780-Cp cells using siRNA greatly reduced the stem cell population and sensitized cells to CDDP. Moreover, silencing of ALDH1A1 reduced the transcript and protein level of its downstream target NEK-2. We also observed the downregulation of ABC transporters (ABCB1/MDR1, ABCG2 and ABCC1/MRP1) either by ALDH1A1 or NEK-2 silencing and upreguation of ABCB1/MDR1 due to the overexpression of NEK-2 . Taken together, the present study suggests that stemness gene ALDH1A1 can be involved in CDDP resistance through the upregulation of NEK-2 in ovarian cancer., Competing Interests: The authors declare no conflict of interest., (© 2020 Published by Elsevier Ltd.)

The unique photophysical properties of lanthanides, such as europium, terbium, and ytterbium, make them versatile molecular probes of biological systems. In particular, their long-lived photoluminescence, narrow bandwidth emissions, and large Stokes shifts enable experiments that are infeasible with organic fluorophores and fluorescent proteins. The ability of these metal ions to undergo luminescence resonance energy transfer, and photon upconversion further expands the capabilities of lanthanide probes. In this review, we describe recent advances in the design of lanthanide luminophores and their application in biological research. We also summarize the latest detection systems that have been developed to fully exploit the optical properties of lanthanide luminophores. We conclude with a discussion of remaining challenges and new frontiers in lanthanide technologies. The unprecedented levels of sensitivity and multiplexing afforded by rare-earth elements illustrate how chemistry can enable new approaches in biology., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Squamous cell carcinomas (SqCCs) of the lung are known to arise more often in a central area but reports of peripheral SqCCs have increased, with a pathogenesis that is obscured. In this study, the clinicopathologic characteristics of peripheral lung SqCCs were studied and compared with those of the central type., Methods: This study included 63 peripheral lung SqCCs and 48 randomly selected central cases; hematoxylin and eosin-stained slides of surgically resected specimens were reviewed in conjunction with radiologic images and clinical history. Cytokeratin-7 immunohistochemical staining of key slides and epidermal growth factor receptor (EGFR)/KRAS mutations tested by DNA sequencing were also included., Results: Stages of peripheral SqCCs were significantly lower than central SqCCs (p=.016). Cystic change of the mass (p=.007), presence of interstitial fibrosis (p=0.007), and anthracosis (p=.049) in the background lung were significantly associated with the peripheral type. Cytokeratin-7 positivity was also higher in peripheral SqCCs with cutoffs of both 10% and 50% (p=.011). Pathogenic mutations in EGFR and KRAS were observed in only one case out of the 72 evaluated. The Cox proportional hazard model indicated a significantly better disease-free survival (p=.009) and the tendency of better overall survival (p=.106) in the peripheral type., Conclusions: In peripheral type, lower stage is a favorable factor for survival but more frequent interstitial fibrosis and older age are unfavorable factors. Multivariate Cox analysis revealed that peripheral type is associated with better disease-free survival. The pathogenesis of peripheral lung SqCCs needs further investigation, together with consideration of the background lung conditions.

Visceral adiposity is closely associated with metabolic disorders and cardiovascular diseases. Angelica gigas Nakai (AGN) has been reported to possess anti-obesity effects and higher amounts of coumarin compounds are present in AGN. However, the active compounds suppressing adipogenesis in AGN and mechanisms of action have not been investigated in adipose-derived stem cells (ASCs) isolated from visceral adipose tissue (VAT). Among four coumarin compounds of AGN, decursin (D) and decursinol angelate (DA) significantly inhibited adipocyte differentiation from ASCs. D and DA downregulated CCAAT/enhancer binding protein α (C/EBPα), peroxisome proliferator-activated receptor γ (PPARγ), adipocyte fatty acid binding protein (aP2), fatty acid synthase (FAS), and acetyl-CoA carboxylase (ACC) at both mRNA and protein levels. Next, treatment with adipogenic differentiation medium (ADM) on ASCs downregulated β-catenin expression at protein level, while addition of D and DA could restore protein expression and nuclear translocation of β-catenin suppressed by ADM. D and DA treatment on ADM treated ASCs increased inhibitory phosphorylation of Glycogen synthase kinase (GSK)-3β, thereby preventing β-catenin from degradation. Additionally, si-β-catenin transfection significantly upregulated protein expression of C/EBPα and PPARγ, alleviating the anti-adipogenic effect of D and DA on ADM treated ASCs. Overall, D and DA, active compounds from AGN, suppressed adipogenesis through activation of β-catenin signaling pathway in ASCs derived from human VAT, possibly using as natural anti-visceral adiposity agents., Competing Interests: The authors declare no conflict of interest.

Mitochondria undergo fission and fusion continually for survival through the course of cellular adaption processes in response to changes in the surrounding environment. Dysregulated mitochondrial dynamics has been reported in various diseases including cancer. Under hypoxic conditions (<1% O 2 ), the relationship between mitochondrial dynamics and sensitivity to cisplatin (CDDP) was examined in ovarian cancer cells. We found that hypoxia promoted mitochondrial fission and CDDP resistance in ovarian cancer cells. Hypoxia-induced reactive oxygen species (ROS) caused an increase in mitochondrial fission, a response abolished by free radical scavenging with N-acetylcysteine (NAC) and Trolox. Also, treatment of hydrogen peroxide (H 2 O 2 ) decreased inhibitory p-Drp1 (Ser637) content and increased mitochondrial fission. Suppression of mitochondrial fission enhanced the CDDP sensitivity of hypoxic ovarian cancer cells. Lastly, in tumor spheroids from malignant ascites or tissues of patients with advanced-stage ovarian cancer, pretreatment with Mdivi-1 increased the CDDP sensitivity. Taken together, our results implicate that hypoxia-induced ROS trigger mitochondrial fission and CDDP resistance through downregulation of p-Drp1 (Ser637) and Mfn1 in ovarian cancer cells. Inhibition of Drp1 by Mdivi-1 treatment or si-Drp1 transfection increased CDDP sensitivity of ovarian cancer cells under hypoxia. Therefore, mitochondrial dynamics of cancer cells adapting to the hypoxic tumor microenvironment could be a potential target for anticancer therapy.

Purpose: Discovery of models predicting the exact prognosis of epithelial ovarian cancer (EOC) is necessary as the first step of implementation of individualized treatment. This study aimed to develop nomograms predicting treatment response and prognosis in EOC., Materials and Methods: We comprehensively reviewed medical records of 866 patients diagnosed with and treated for EOC at two tertiary institutional hospitals between 2007 and 2016. Patients' clinico-pathologic characteristics, details of primary treatment, intra-operative surgical findings, and survival outcomes were collected. To construct predictive nomograms for platinum sensitivity, 3-year progression-free survival (PFS), and 5-year overall survival (OS), we performed stepwise variable selection by measuring the area under the receiver operating characteristic curve (AUC) with leave-one-out cross-validation. For model validation, 10-fold cross-validation was applied., Results: The median length of observation was 42.4 months (interquartile range, 25.7 to 69.9 months), during which 441 patients (50.9%) experienced disease recurrence. The median value of PFS was 32.6 months and 3-year PFS rate was 47.8% while 5-year OS rate was 68.4%. The AUCs of the newly developed nomograms predicting platinum sensitivity, 3-year PFS, and 5-year OS were 0.758, 0.841, and 0.805, respectively. We also developed predictive nomograms confined to the patients who underwent primary debulking surgery. The AUCs for platinum sensitivity, 3-year PFS, and 5-year OS were 0.713, 0.839, and 0.803, respectively., Conclusion: We successfully developed nomograms predicting treatment response and prognosis of patients with EOC. These nomograms are expected to be useful in clinical practice and designing clinical trials.

Background: Human leukocyte antigen class I (HLA-I) molecules play important roles in regulating immune responses. Loss or reduction of HLA-I expression has been shown to be associated with prognosis in several cancers. Regulatory T-cells (Tregs) also play critical functions in immune response regulation. Evaluation of HLA-I expression status by the EMR8-5 antibody and its clinical impact in breast cancer have not been well studied, and its relationship with Tregs remains unclear., Methods: We evaluated HLA-I expression and Treg infiltration by immunohistochemistry in 465 surgically resected breast cancer samples. We examined the correlation between HLA-I expression and Treg infiltration and clinicopathologic characteristics and survival analyses were performed., Results: Total loss of HLA-I expression was found in 84 breast cancer samples (18.1%). Univariate survival analysis revealed that loss of HLA-I expression was significantly associated with worse disease-specific survival (DSS) (p = .029). HLA-I was not an independent prognostic factor in the entire patient group, but it was an adverse independent prognostic factor for DSS in patients with advanced disease (stage II-IV) (p = .031). Treg numbers were significantly higher in the intratumoral stroma of HLA-I-positive tumors than in HLA-I-negative tumors (median 6.3 cells/high power field vs 2.1 cells/high power field, p < .001). However, Tregs were not an independent prognostic factor in our cohort., Conclusions: Our findings suggest that the loss of HLA-I expression is associated with poor prognosis in breast cancer patients, highlighting the role of HLA-I alterations in immune evasion mechanisms of breast cancer. HLA-I could be a promising marker that enables the application of more effective and precise immunotherapies for patients with advanced breast cancer.

Systemic inflammatory markers derived from peripheral blood cell, such as the neutrophil-lymphocyte ratio (NLR), derived neutrophil-lymphocyte ratio (dNLR), platelet-lymphocyte ratio (PLR) and lymphocyte-monocyte ratio (LMR), have been demonstrated as prognostic markers in several types of malignancy. Here, we investigated and compared the association between systemic inflammatory markers and survival and developed a prognostic nomogram in breast cancer patients. We reviewed the clinical and pathological records of 661 patients diagnosed with invasive breast carcinoma between 1993 and 2011. The NLR, dNLR, PLR and LMR in the immediate preoperative period were assessed. We analyzed the relationship between these inflammatory markers and clinicopathologic variables, disease-specific survival (DSS), and disease-free survival (DFS) in patients. A nomogram was developed to predict 3- and 5-year DSS for breast cancer. In the univariate analysis, high NLR, dNLR, PLR and low LMR were all significantly associated with poor DSS and DFS. In the multivariate analysis, only the PLR (HR 3.226, 95% CI 1.768-5.885 for DSS and HR 1.824, 95% CI 1.824-6.321 for DFS) was still identified as an independent predictor of outcomes. A subgroup analysis revealed that the PLR was the sole independent marker predicting poor DSS in patients with lymph node metastasis (HR 2.294, 95% CI 1.102-4.777) and with luminal subtype (HR 4.039, 95% CI 1.905-8.562). The proposed nomogram, which includes the PLR, shows good accuracy in predicting DSS with a concordance index of 0.82. PLR is an indicator of systemic inflammation as a part of the host immune response. As an independent prognostic factor, an elevated preoperative PLR is superior to the NLR, dNLR, and LMR in predicting clinical outcomes in patients with breast cancer. Moreover, the nomogram incorporating the PLR could accurately predict individualized survival probability in breast cancer., Competing Interests: The authors have declared that no competing interests exist.

Background: Due to morphologic similarities between undifferentiated sarcoma (US) and dedifferentiated liposarcoma (DDLPS), some portions of US could be identified as DDLPS. In this study, we applied adipocyte-related antibodies in order to discriminate possible cases of DDLPS from US., Materials and Methods: A total of 46 cases, previously diagnosed as US, were examined. Immunohistochemistry for MDM2, CDK4, calreticulin, FABP4, and stathmin were performed. Histological findings were reviewed and clinical data was analyzed retrospectively., Results: MDM2, CDK4, calreticulin, FABP4, and stathmin were positive in 17 (37.0%), 14 (30.4%), 3 (6.5%), 1 (2.2%), and 12 (26.1%) of the total 46 cases, respectively. MDM2/CDK4 positive cases showed more frequent positivity for calreticulin/FABP4/stathmin. Survival analysis, based on staining pattern, revealed a significantly better survival in the group where either MDM2 and CDK4 were positive and at least one of calreticulin, FABP4, or stathmin staining were positive., Conclusions: We conclude that when either MDM2-positive or CDK4-positive cases show any other positive results for calreticulin, FABP4, or stathmin, they have a significantly better survival and the possibility of DDLPS should be considered. Additional use of calreticulin, FABP4, or stathmin immunohistochemistry helps us to narrow the pool for further studies such as molecular analysis for a definite diagnosis., Competing Interests: None., (IJCEP Copyright © 2018.)

Thyroid tumors formerly classified as non-invasive encapsulated follicular variant of papillary thyroid carcinoma were recently renamed 'non-invasive follicular thyroid neoplasm with papillary-like nuclear features'. The current study investigated the frequency of lymph node metastasis and mutational profile of encapsulated follicular variant in the setting of a clinical practice where central neck dissection was the standard of practice. We defined the impact of rigid diagnostic criteria by regrouping such tumors based on the complete absence of papillae or presence of ≤1% papillae. Of a total of 6,269 papillary thyroid carcinomas, 152 tumors fulfilled the criteria for encapsulated follicular variant. The results were stratified according to two different diagnostic cutoff criteria with respect to the extent of papillae. When the cutoff of 1% papillae was used, the rates of lymph node metastasis and BRAF V600E mutation were 3% and 10% in non-invasive tumors and 9% and 4% in invasive tumors, respectively. Despite the lack of invasive growth, one patient with BRAF V600E mutant-tumor displaying predominant follicular growth and subtle papillae developed a bone metastasis. When absence of papillary structure was applied as rigid diagnostic criteria, no BRAF V600E mutation was found in all tumors. However, central lymph node micrometastasis still occurred in 3% of non-invasive tumors. Non-V600E BRAF and RAS mutations were detected in 4% and 47% of non-invasive tumors, respectively. Our findings suggest that non-invasive follicular thyroid neoplasm with papillary-like nuclear features should not be regarded as a benign thyroid neoplasm as it can present with lymph node micrometastasis and should not be diagnosed in the presence of even a single papillary structure. Our findings underscore the original American Thyroid Association recommendation that defined non-invasive encapsulated follicular variants as low risk thyroid cancers. Clinical surveillance similar to low risk differentiated thyroid cancers and capture of this diagnostic category by Cancer Registries should be considered.

We report a new α-Galactosidase A (αGal-A) mutation in a 39-year-old Korean born, male Fabry disease patient. Fabry disease is a devastating, progressive inborn error of metabolism caused by X-linked genetic mutations. In this case, the first clinical symptom to occur was in childhood consisting of a burning pain originating in the extremities then radiating inwards to the limbs. This patient also stated to have ringing in his ears, angiokeratomas on his trunk, and cornea verticillata. He visited an outpatient cardiologist due to intermittent and atypical chest discomfort at the age of 39. Electrocardiographic and echocardiographic examination showed left ventricular hypertrophy. A physical examination revealed proteinuria without hematuria. The patient's plasma αGal-A activity was markedly lower than the mean value of the controls. After genetic counseling and obtaining written informed consent, we identified one hemizygous mutation in exon 4 of galactosidase alpha, c.617T>C (p.Leu206 Pro). He was eventually diagnosed as having Fabry disease., Competing Interests: The authors have no financial conflicts of interest.