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AIMS: To investigate the effects of morphine on mechanical allodynia following compression of the trigeminal ganglion in the rat. METHODS: Experiments were carried out on male Sprague-Dawley rats weighing between 250 and 260 g. For compression, a 4% agar solution (8 microL) was injected into the trigeminal ganglion. In the control group, rats were sham operated without agar injections. The authors evaluated the effects of intraperitoneal or intracisternal administration of morphine on mechanical allodynia evoked by air-puff stimulation of the vibrissa pad area 14 days following compression of the trigeminal ganglion. RESULTS: Mechanical allodynia was established within 3 days and lasted beyond postoperative day 24. Intraperitoneal administration of morphine (2 or 5 mg/kg) significantly blocked mechanical allodynia ipsilateral to the compression of the trigeminal ganglion. Intraperitoneal administration of morphine also inhibited mechanical allodynia on the contralateral side. Moreover, intracisternal administration of morphine (5 microg) strongly suppressed both ipsilateral and contralateral mechanical allodynia. The antiallodynic effects of morphine were blocked by pretreatment with naloxone, an opioid receptor antagonist. CONCLUSION: These results suggest that the application of a high dose of morphine may be of great benefit in treating trigeminal neuralgia-like nociception. [ABSTRACT FROM AUTHOR]

Background: Although the criteria for follicular-pattern thyroid tumors are well-established, diagnosing these lesions remains challenging in some cases. In the recent World Health Organization Classification of Endocrine and Neuroendocrine Tumors (5th edition), the invasive encapsulated follicular variant of papillary thyroid carcinoma was reclassified as its own entity. It is crucial to differentiate this variant of papillary thyroid carcinoma from low-risk follicular pattern tumors due to their shared morphological characteristics. Proteomics holds significant promise for detecting and quantifying protein biomarkers. We investigated the potential value of a protein biomarker panel defined by machine learning for identifying the invasive encapsulated follicular variant of papillary thyroid carcinoma, initially using formalin- fixed paraffin-embedded samples., Methods: We developed a supervised machine-learning model and tested its performance using proteomics data from 46 thyroid tissue samples., Results: We applied a random forest classifier utilizing five protein biomarkers (ZEB1, NUP98, C2C2L, NPAP1, and KCNJ3). This classifier achieved areas under the curve (AUCs) of 1.00 and accuracy rates of 1.00 in training samples for distinguishing the invasive encapsulated follicular variant of papillary thyroid carcinoma from non-malignant samples. Additionally, we analyzed the performance of single-protein/gene receiver operating characteristic in differentiating the invasive encapsulated follicular variant of papillary thyroid carcinoma from others within The Cancer Genome Atlas projects, which yielded an AUC > 0.5., Conclusions: We demonstrated that integration of high-throughput proteomics with machine learning can effectively differentiate the invasive encapsulated follicular variant of papillary thyroid carcinoma from other follicular pattern thyroid tumors.

Background: The possible association between diabetes mellitus and dementia has raised concerns, given the observed coincidental occurrences., Objective: This study aims to develop a personalized predictive model, utilizing artificial intelligence, to assess the 5-year and 10-year dementia risk among patients with Type 2 Diabetes Mellitus (T2DM) who are prescribed antidiabetic medications., Methods: This retrospective multicenter study used data from Taipei Medical University Clinical Research Database, which comprises electronic medical records from three hospitals in Taiwan. This study applied eight machine learning algorithms to develop prediction models, including logistic regression (LR), linear discriminant analysis (LDA), gradient boosting machine (GBM), lightGBM (LBGM), AdaBoost, random forest, extreme gradient boosting (XGBoost), and artificial neural network (ANN). These models incorporated a range of variables, encompassing patient characteristics, comorbidities, medication usage, laboratory results, and examination data., Results: This study involved a cohort of 43,068 patients diagnosed with T2DM, which accounted for a total of 1,937,692 visits. For model development and validation, 1,300,829 visits were utilized, while an additional 636,863 visits were reserved for external testing. The area under the curve (AUC) of the prediction models range from 0.67 for the logistic regression to 0.98 for the artificial neural networks. Based on the external test results, the model built using the ANN algorithm has the best AUC: 0.97 (5-year follow-up period) and 0.98 (10-year follow-up period). Based on the best model (ANN), age, gender, triglyceride, HbA1c, anti-diabetic agents, stroke history, and other long-term medications were the most important predictors., Conclusions: We have successfully developed a novel computer-aided dementia risk prediction model that can facilitate the clinical diagnosis and management of patients prescribed with antidiabetic medications. However, further investigation is required to assess the model's feasibility and external validity.

Introduction: PReferentially expressed Antigen in MElanoma (PRAME) has shown utility in differentiating benign from malignant melanocytic neoplasms. In this study, we investigated the clinical significance of PRAME expression in dysplastic nevi (DN) and nevus-associated melanoma in situ (MIS)., Methods: We included 172 DN and 38 nevus-associated MIS from our institutional archive. PRAME positive expression was defined as nuclear staining in at least 75% of melanocytes. In addition, relevant studies from PubMed and Web of Science were incorporated into a meta-analysis using the random-effects model to assess PRAME expression in MIS and DN., Results: Our institutional data revealed that 71.1% of nevus-associated MIS cases exhibited positive PRAME expression in the MIS components, whereas all DN components were negative for PRAME. 5.7% of cases diagnosed as DN in our cohort demonstrated diffuse positivity for PRAME. Notably, MIS associated with DN displaying epidermal and dermal components displayed a higher likelihood of PRAME positivity compared to those arising on a background of DN with solely epidermal (junctional) components (84% vs. 46%, p = 0.024). The meta-analysis indicated that the pooled PRAME positivity in MIS and DN was 54.5% and 1.9%, respectively., Conclusion: PRAME is a valuable immunohistochemical marker for differentiating MIS from DN, particularly in the context of nevus-associated MIS., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Purpose: Although some immune protection from close contact with individuals who have coronavirus disease 2019 (COVID-19) has been documented, there is limited data on the seroprevalence of antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in individuals who were in lockdown with confirmed COVID-19 cases. This study investigated immunogenicity against SARS-CoV-2 in household members and people who lived near home-quarantined patients with COVID-19., Materials and Methods: This cross-sectional study was conducted during the community-based care that took place during lockdowns in District 10, Ho Chi Minh City, Vietnam from July to September 2021. SARS-CoV-2 antibody levels were determined in index cases of COVID-19, household contacts, and a no-contact group from the same area., Results: A total of 770 participants were included (355 index cases, 103 household contacts, and 312 no contacts). All index cases were unvaccinated, but >90% of individuals in the household and no-contact groups had received ≥1 vaccine dose. SARS-CoV-2 neutralizing antibodies (Nabs) were present in >77% of unvaccinated index cases versus 64%/65.4% in the household/no-contact groups ( p =0.001). Antibody concentrations in unvaccinated index cases were significantly higher than those in household contacts and no contacts, with no difference between the latter groups. In all cases, antibody levels declined markedly ≥6 weeks after infection, and failed to persist beyond this time in the household and no-contact groups., Conclusion: Community-based care may have helped to create community immunogenicity, but Nabs did not persist, highlighting a need for vaccination for all individuals before, or from 6 weeks after, infection with SARS-CoV-2., Competing Interests: The authors have no potential conflicts of interest to disclose., (© Copyright: Yonsei University College of Medicine 2024.)

Background: C-X-C motif chemokine ligand 5 (CXCL5) is a chemokine molecule that is secreted by immune cells in attracting granulocytes. Studies showed that CXCL5 was related to the progression of papillary thyroid carcinoma (PTC) tumor cells. However, the in vivo effects of CXCL5 on PTC tumor cells and their microenvironment have not been elucidated. The present study aimed to investigate the biological effects of CXCL5 on tumor cells, microenvironment, and clinical progression of PTC., Materials and Methods: The PTC patients from The Human Cancer Genome Atlas (TCGA) - thyroid carcinoma (THCA) were retrieved. There were a total of 500 patients who met the criteria of our study. Differential expression (DEA) and pathway analyses were used to explore the biological effects of CXCL5 gene expression., Results: In DEA, we found that CXCL5 was mostly associated with PBPP, SLC11A1, and MRC1 (adjusted p<0.001). Samples with CXCL5 FPKM≥1 were related to a different immune profile (p<0.001). In pathway analyses, samples with higher CXCL5 expression possessed higher activities of RAS-RAF, NF-kB, PRC2, IL2, IL5, and Wnt pathways (adjusted p<0.001). In microenvironment analysis, CXCL5 was highly correlated with the activity of macrophage (Rho=0.76; adjusted p<0.001). Clinically, high level of CXCL5 expression was an indicator of tumor stages (p<0.001), nodal metastasis (AUC=0.68), and prognosis (p=0.001)., Conclusion: CXCL5 was a significant biomarker of PTC. CXCL5 was highly associated with tumor immunology and microenvironment. Samples with higher CXCL5 expression had more advanced disease status and worse prognosis. CXCL5 target therapy is potentially helpful in advanced PTC., Competing Interests: Declaration of Competing Interest No conflict of interest, (Copyright © 2024. Published by Elsevier GmbH.)

The circadian clock (CC) has biological and clinical implications in gliomas. Most studies focused on CC effects on the tumor microenvironment and the application of chronotherapy. The present study focused on CC gene expression patterns and intracellular oncogenic activities. Glioma gene expression data were collected from The Human Cancer Genome Atlas (TCGA) project. After applying inclusion and exclusion criteria, we selected 666 patients from TCGA-GBM and TCGA-LGG projects and included important clinicopathological variables. The entire cohort was subjected to clustering analysis and divided into CC1 and CC2 subtypes based on statistical, biological, and clinical criteria. CC2 gliomas showed higher expression of BMAL1 and CRY1 and lower expression of CRY2 and PER2 (adjusted P < .001). CC2 gliomas had q higher activity of cell proliferation, metabolic reprogramming, angiogenesis, hypoxia, and many oncogenic signals (P < .001). The CC2 subtype contained a higher proportion of glioblastomas (P < .001) and had a worse prognosis (P < .001). Stratified Kaplan-Meier and multivariable Cox analyses illustrated that the CC subtype is an independent prognostic factor to clinicopathological characteristics (P < .001), genetic aberrations (P = .006), and biological processes (P < .001). Thus, this study shows statistical evidence of CC subtypes and their biological, and clinicopathological significance in adult gliomas., (© The Author(s) 2024. Published by Oxford University Press on behalf of American Association of Neuropathologists, Inc. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Tumor-stroma ratio (TSR) has been recognized as a valuable prognostic indicator in various solid tumors. This study aimed to examine the clinicopathologic relevance of TSR in Merkel cell carcinoma (MCC) using artificial intelligence (AI)-based parameterization of the stromal landscape and validate TSR scores generated by our AI model against those assessed by humans. One hundred twelve MCC cases with whole-slide images were collected from 4 different institutions. Whole-slide images were first partitioned into 128 × 128-pixel "mini-patches," then classified using a novel framework, termed pre-tumor and stroma (Pre-TOAST) and TOAST, whose output equaled the probability of the minipatch representing tumor cells rather than stroma. Hierarchical random samplings of 50 minipatches per region were performed throughout 50 regions per slide. TSR and tumor-stroma landscape (TSL) parameters were estimated using the maximum-likelihood algorithm. Receiver operating characteristic curves showed that the area under the curve value of Pre-TOAST in discriminating classes of interest including tumor cells, collagenous stroma, and lymphocytes from nonclasses of interest including hemorrhage, space, and necrosis was 1.00. The area under the curve value of TOAST in differentiating tumor cells from related stroma was 0.93. MCC stroma was categorized into TSR high (TSR ≥ 50%) and TSR low (TSR < 50%) using both AI- and human pathology-based methods. The AI-based TSR-high subgroup exhibited notably shorter metastasis-free survival (MFS) with a statistical significance of P = .029. Interestingly, pathologist-determined TSR subgroups lacked statistical significance in recurrence-free survival, MFS, and overall survival (P > .05). Density-based spatial clustering of applications with noise analysis identified the following 2 distinct TSL clusters: TSL1 and TSL2. TSL2 showed significantly shorter recurrence-free survival (P = .045) and markedly reduced MFS (P < .001) compared with TSL1. TSL classification appears to offer better prognostic discrimination than traditional TSR evaluation in MCC. TSL can be reliably calculated using an AI-based classification framework and predict various prognostic features of MCC., (Copyright © 2024 United States & Canadian Academy of Pathology. Published by Elsevier Inc. All rights reserved.)

Acquired cystic disease-associated renal cell carcinoma (ACD-RCC) is a common subtype of renal cell carcinoma (RCC) in end-stage renal disease (ESRD) patients. The current systematic review and meta-analysis was performed to evaluate the clinicopathological, and genetic characteristics of patients with ACD-RCC. A systematic search on three electronic databases including the Pubmed, Scopus, and Web of Science databases were performed until December 31, 2022. A meta-analysis was performed following the PRISMA 2020 Guidelines. Of 888 identified articles, full-text screening in 69 articles, there were 26 articles analyzed, with a total of 2314 tumors in 2199 patients, including 418 ACD-RCC tumors in 363 patients, 1340 clear cell RCC (ccRCC) tumors, 308 papillary RCC (pRCC) tumors. Most ACD-RCC patients were male (80.2%). All the ACD-RCC patients underwent prior dialysis with 148.2 months of mean dialysis duration. There were 8.7%, 3.4%, and 5.8% tumors at the T3-4 stage, N1 stage, and M1 stage, respectively. The mean overall survival of ACD-RCC patients was 39.6 months (95% CI, 26.6-52.5). Compared to ccRCC and pRCC, ACD-RCC patients had a longer duration of dialysis (MD: 103.5 and 31.77 months, respectively; 95% CI: [75.48; 131.53] and [0.95; 62.58], respectively), and a higher rate of multifocal tumors (MD: 3.46 and 2.45 tumors, respectively; 95% CI [1.71; 6.98] and [1.26; 4.79], respectively). Regarding genetic characteristics, chromosomes 3 and 16 were the 2 most frequent chromosomal aberrations. The missense mutation in KMT2C (25%) and TSC2 (18.75%) were the 2 most common gene mutations in ACD-RCC. In conclusion, the ACD-RCC subtype exhibited several distinct clinicopathological and genetic characteristics compared to others RCC subtypes. Further researchs are needed to assess the survival outcome and the genetic characteristics of this subtype., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Introduction: We aimed to investigate the expression and prognostic role of NAA10 in clear cell renal cell carcinoma (ccRCC)., Material and Methods: We performed a gene expression and survival analysis based on the human cancer genome atlas database of ccRCC patients (TCGA-KIRC)., Results: The patients in the TCGA-KIRC (n = 537) were divided into two subgroups: NAA10-low and NAA10-high expression groups. NAA10-high ccRCC exhibited higher T stages (p = 0.002), a higher frequency of distant metastasis (p = 0.018), more advanced AJCC stages (p < 0.001), a lower overall survival time (p = 0.036), and a lower survival rate (p < 0.001). NAA10-high ccRCC was associated with increased activity of non-specific oncogenic pathways, including oxidative phosphorylation (p < 0.001) and cell cycle progression [G2 to M phase transition (p = 0.045) and E2F targets (p < 0.001)]. Additionally, the NAA10-high tumors showed reduced apoptosis via TRIAL pathways (p < 0.001) and increased levels of activity that promoted epithelial-mesenchymal transition (p = 0.026) or undifferentiation (p = 0.01). In ccRCC, NAA10 expression was found to be a negative prognostic factor in both non-metastatic (p < 0.001) and metastatic tumors (p = 0.032)., Conclusions: In ccRCC, NAA10 expression was shown to be a negative prognostic factor related to tumor progression rather than tumor initiation, and high NAA10 expression promoted epithelial-mesenchymal transition and undifferentiation., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest., (Copyright © 2024. Published by Elsevier GmbH.)

New applications of immunohistochemistry (IHC) expand rapidly due to the development of molecular analyses and an increased understanding of molecular biology. IHC becomes much more important as a screening or even a confirmatory test for molecular changes in cancer. The past decades have witnessed the release of many immunohistochemical markers of the new generation. The novel markers have extensively high specificity and sensitivity for the detection of genetic abnormalities. In addition to diagnostic utility, IHC has been validated to be a practical tool in terms of treatments, especially molecular targeted therapy. In this review, we first describe the common alterations of protein IHC staining in human cancer: overexpression, underexpression, or loss of expression and altered staining pattern. Next, we examine the relationship between staining patterns and genetic aberrations regarding both conventional and novel IHC markers. We also mention current mutant-specific and fusion-specific antibodies and their concordance with molecular techniques. We then describe the basic molecular mechanisms from genetic events to corresponding protein expression patterns (membranous, cytoplasmic, or nuclear patterns). Finally, we shortly discuss the applications of immunohistochemistry in molecular targeted therapy. IHC markers can serve as a complementary or companion diagnostic test to provide valuable information for targeted therapy. Moreover, immunohistochemistry is also crucial as a companion diagnostic test in immunotherapy. The increased number of IHC novel antibodies is broadening its application in anti-cancer therapies., Competing Interests: Declaration of Competing Interest no conflict., (Copyright © 2024 Elsevier GmbH. All rights reserved.)

Introduction: Atopic dermatitis (AD) is characterized by an impaired epidermal barrier, which could be associated with sensitization to food allergens (FAs) and/or inhaled allergens and contribute to the severity of AD. However, no clinical guidance has been established for evaluations of food sensitization (FS) in AD patients. This study investigated how AD severity and epidermal barrier impairment are associated with FS and factors that can predict FS in children with AD., Methods: This cross-sectional study included 100 children (12-60 months) diagnosed with AD. AD severity was determined using the Scoring Atopic Dermatitis (SCORAD) index. FS was evaluated by measuring serum-specific IgE antibodies against 31 FAs using an immunoblotting method. Epidermal barrier impairment was assessed by measuring transepidermal water loss (TEWL) and stratum corneum hydration (SCH) levels., Results: 90% of participants were sensitized to at least one tested FA, with cow's milk, egg white, beef, almond, egg yolk, and peanut being the most common. Children with moderate-severe AD had lower SCH levels than those with mild AD. Children with AD who were sensitized to &gt;10 FAs had significantly higher TEWL and lower SCH levels, compared with those sensitized to 1-4 FAs and 5-10 FAs. The SCORAD score and SCH level in lesional skin provided moderately predictive value for sensitization to FAs in children with AD., Conclusion: FS is common in children with AD and closely associate with AD severity as well as epidermal barrier impairment. Evaluations of FS should be considered for children with moderate to severe AD and/or low SCH levels., (© 2023 S. Karger AG, Basel.)

Extranodal NK/T-cell lymphoma (ENKTL) generally expresses cytotoxic molecules, including granzyme B (GZMB), T-cell-restricted intracellular antigen-1 (TIA-1), and perforin; however, the expression of these molecules varies across cases. We performed gene expression profiling and identified unique biological and clinicopathological features of GZMB-negative ENKTL. We reviewed the clinicopathological characteristics of 71 ENKTL samples. Gene expression profiling on nine ENKTLs using multiplexed, direct, and digital mRNA quantification divided ENKTLs into Groups A (n = 7) and B (n = 2) through hierarchical clustering and t-distributed stochastic neighbor embedding. Group B was characterized by downregulation of genes associated with IL6-JAK-STAT3 signaling and inflammatory responses. GZMB mRNA expression was significantly downregulated in Group B. GZMB protein expression was evaluated with immunohistochemistry in all 71 ENKTLs, and expression data of Tyr705-phosphorylated STAT3 (pSTAT3) and MYC from our previous study was utilized. T-cell receptor gamma (TRG) gene rearrangement in the selected samples was also assessed using PCR. GZMB expression was higher in pSTAT3-positive (p = 0.028) and MYC-positive (p = 0.014) ENKTLs. Eighteen percent (13/71) of all ENKTLs were negative for GZMB (defined by positivity <10 %); patients with GZMB-negative ENKTLs were often in a higher clinical stage (p = 0.016). We observed no other correlations with clinical parameters or TRG rearrangement and no significant association between GZMB expression and survival. In conclusion, GZMB expression is highly heterogeneous in ENKTLs and is associated with the activation of the JAK-STAT3 pathway and higher MYC expression. GZMB-negative ENKTLs correlate with an advanced clinical stage, suggesting the potential utility of GZMB immunohistochemistry as a biomarker of ENKTL., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Claudin-4 is a key component of tight junctions, which play an important role in the formation of the epidermal barrier by forming a circumferential network in the granular layer that serves as a gatekeeper of the paracellular pathway. The aim of this study is to illustrate claudin-4 immunohistochemical staining patterns of different blistering disorders. We collected 35 cases, including two Hailey-Hailey disease, one Darier disease, three Grover disease, one acantholytic acanthoma, two warty dyskeratoma, 11 pemphigus vulgaris (PV) including six mucosal PV, and two pemphigus foliaceus. For comparison, we included five cases of normal skin, five eczema, and three bullous pemphigoid cases. Claudin-4 demonstrated weak-to-moderate expression in keratinocytes located in the stratum granulosum, keratinocytes surrounding hair follicles, and adnexal glands. Further, claudin-4 exhibited moderate-to-strong membranous staining in disrupted keratinocytes surrounding and within the acantholytic and bullous areas in 16/22 of the acantholytic cases (not seen in the six cases of mucosal PV) and all three bullous pemphigoids. This finding suggests that claudin-4 is upregulated in these conditions, which may be a compensatory response to the disrupted barrier function. This finding could shed light on the molecular mechanisms underlying disrupted barrier function in blistering disorders, independent of the specific underlying disease mechanism.

Background: SLC22A3 , the gene which encodes organic cation transporter (OCT)-3, has been linked to the prognosis of several types of cancer. However, its role in lung squamous cell carcinoma (LSCC) has not been addressed elsewhere., Methods: We analyzed gene expression, DNA methylation, and clinicopathological data from The Cancer Genome Atlas - Lung Squamous Cell Carcinoma (TCGA-LUSC) (n=501), a publicly available database exclusively consisting of LSCC patients. Using a 5 FPKM (fragments per kilobase of exon per million mapped fragments) cut-off, we divided LSCC patients into two groups: patients with tumors possessing high and low SLC22A3 expression ( SLC22A3 -high and SLC22A3 -low, respectively). Prognostic significance was determined through Cox analyses and Kaplan-Meier curves for overall survival (OS) and disease-free survival (DFS). Differential methylation position (DMP), differentially gene expression, and pathway analyses were performed. Validation was carried out in GSE74777 (n=107), GSE37745 (n=66), GSE162520 (n=45) and GSE161537 (n=17)., Results: SLC22A3 -high LSCC patients had lower OS and DFS rates than SLC22A3 -low LSCC patients. The different expression levels of SLC22A3 in LSCC were correlated with the methylation status of the SLC22A3 gene. Pathway analysis indicated that SLC22A3 expression levels were positively correlated with immune-related pathways such as inflammatory response and abundance of infiltrating immune cells in the tumor microenvironment (TME). Notably, in the SLC22A3 -high group, many genes encoding immunological checkpoint inhibitory molecules were upregulated. In addition, SLC22A3 expression positively correlated with the Hot Oral Tumor (HOT) score, indicating high tumor immunogenicity., Conclusions: These findings suggest that high expression of SLC22A3 is associated with poor prognosis and high immunogenicity in LSCC tumors., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-23-334/coif). The authors have no conflicts of interest to declare., (2023 Translational Lung Cancer Research. All rights reserved.)

Background: PRAME (PReferentially expressed Antigen in MElanoma) is a biomarker studied in various human cancers. Little is known about the biological implications of PRAME in glioma. We aimed to perform a comprehensive analysis to explore PRAME gene expression and its biological and clinicopathological significance in gliomas., Methods and Materials: We accessed the human cancer atlas (TCGA) database to collect glioma patients (n = 668) with primary tumors and gene expression data. Single nucleotide variants, copy number variation, DNA methylation data, and other clinicopathological factors were also extracted for the analysis., Results: Overall, 170, 484, and 14 tumors showed no expression, low expression (FPKM≤1), and overexpression (FPKM>1) of the PRAME gene, respectively. The principal component analysis and pathway analyses showed that PRAME-positive gliomas (n = 498), which consisted of tumors with PRAME low expression and overexpression, expressed different oncogenic profiles, possessing higher activity of Hedgehog, P3IK-AKT-mTOR, and Wnt/β-catenin pathways (p<0.001). DNA methylation analysis also illustrated that PRAME-positive tumors were distributed more densely within a grade 4-related cluster (p<0.001). PRAME positivity was an independent prognostic factor for poor outcomes in a multivariate cox analysis adjusted for clinical characteristics and genetic events. Kaplan-Meier analysis stratified by revised classification showed that PRAME positivity was solely associated with IDH-wildtype glioblastoma, grade 4. Finally, PRAME-overexpressing cases (n = 14) had the worst clinical outcome compared to the PRAME-negative and PRAME-low cohorts (adjusted p<0.001) in pairwise comparisons., Conclusion: PRAME expression statuses may dictate different biological and clinicopathological profiles in IDH-wildtype glioblastoma., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Le 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.)

Background: Stratify new lung cancer patients based on the risk of in-hospital mortality rate after diagnosis. Methods: 522,941 lung cancer cases with available data on the Surveillance, Epidemiology, and End Results (SEER) were analyzed for the predicted probability based on six fundamental variables including age, gender, tumor size, T, N, and AJCC stages. The patients were randomly assigned to the training ( n = 115,145) and validation datasets ( n = 13,017). The remaining cohort with missing values ( n = 394,779) was then combined with the primary lung tumour datasets ( n = 1018) from The Cancer Genome Atlas, Lung Adenocarcinoma and Lung Squamous Cell Carcinoma projects (TCGA-LUAD & TCGA-LUSC) for external validation and sensitivity analysis. Results: Receiver Operating Characteristic (ROC) analyses showed high discriminatory power in the training and internal validation cohorts (Area under the curve [AUC] of 0.78 (95%CI = 0.78-0.79) and 0.78 (95%CI = 0.77-0.79), respectively), whereas that of the model on external validation data was 0.759 (95%CI = 0.757-0.761). We developed a static nomogram, a web app, and a risk table based on a logistic regression model using algorithm-selected variables. Conclusions: Our model can stratify lung cancer patients into high- and low-risk of in-hospital mortality to assist clinical further planning.

Metallothermic, especially magnesiothermic, solid-state reactions have been widely applied to synthesize various materials. However, further investigations regarding the use of this method for composite syntheses are needed because of the high reactivity of magnesium. Herein, we report an in situ magnesiothermic reduction to synthesize a composite of Ge@C as an anode material for lithium-ion batteries. The obtained electrode delivered a specific capacity of 454.2 mAh·g -1 after 200 cycles at a specific current of 1000 mA·g -1 . The stable electrochemical performance and good rate performance of the electrode (432.3 mAh·g -1 at a specific current of 5000 mA·g -1 ) are attributed to the enhancement in distribution and chemical contact between Ge nanoparticles and the biomass-based carbon matrix. A comparison with other synthesis routes has been conducted to demonstrate the effectiveness of contact formation during in situ synthesis., (Copyright © 2023, Tran Huu et al.)

NAA10 is a novel biomarker of cancer progression. The oncogenic and biological mechanisms of NAA10 in human malignancies are controversial and remain to be elucidated. Herein, we investigated the biological and clinicopathological implications of NAA10 gene expression in adult gliomas. We collected data from The Human Cancer Genome Atlas (TCGA) database, including patients from TCGA-GBM and TCGA-LGG projects. In total, there were 666 patients from the 2 projects (513 and 153 from TCGA-LGG and TCGA-GBM, respectively). Different analyses (pathway, DNA methylation, and survival analyses) require further specific case eliminations. Based on NAA10 expression, we divided 666 tumors into 2 subgroups: NAA10-high and NAA10-low glioma. There were higher activities of cell proliferation, metabolic reprogramming, DNA repair, angiogenesis, epithelial-mesenchymal transition, TNF-α, IL6/JAK/STAT6, mTORC1 signaling, and MYC targets in NAA10-high glioma, while P53, TGF-β, Wnt, and Hedgehog pathways were highly expressed by NAA10-low gliomas. t-distributed stochastic neighbors embedding dimension reduction of DNA methylation also showed a high distribution of NAA10-high gliomas in distinct clusters. Survival analyses showed that high NAA10 expression was an independent prognostic factor. NAA10 expression dictated epigenetic, genetic, and clinicopathological differences in adult glioma. Further studies are required to investigate the detailed NAA10 oncogenic mechanisms and to validate NAA10 immunohistochemistry., (© The Author(s) 2023. Published by Oxford University Press on behalf of American Association of Neuropathologists, Inc. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objectives: Many interventions in bronchiolitis are low-value or poorly studied. Inpatient bronchiolitis management is multidisciplinary, with varying degrees of registered nurse (RN) and respiratory therapist (RT) autonomy. Understanding the perceived benefit of interventions for frontline health care personnel may facilitate deimplementation efforts. Our objective was to examine perceptions surrounding the benefit of common inpatient bronchiolitis interventions., Methods: We conducted a cross-sectional survey of inpatient pediatric RNs, RTs, and physicians/licensed practitioners (P/LPs) (eg, advanced-practice practitioners) from May to December of 2021 at 9 university-affiliated and 2 community hospitals. A clinical vignette preceded a series of inpatient bronchiolitis management questions., Results: A total of 331 surveys were analyzed with a completion rate of 71.9%: 76.5% for RNs, 57.4% for RTs, and 71.2% for P/LPs. Approximately 54% of RNs and 45% of RTs compared with 2% of P/LPs believe albuterol would be "extremely or somewhat likely" to improve work of breathing (P < .001). Similarly, 52% of RNs, 32% of RTs, and 23% of P/LPs thought initiating or escalating oxygen in the absence of hypoxemia was likely to improve work of breathing (P < .001). Similar differences in perceived benefit were observed for steroids, nebulized hypertonic saline, and deep suctioning, but not superficial nasal suctioning. Hospital type (community versus university-affiliated) did not impact the magnitude of these differences., Conclusions: Variation exists in the perceived benefit of several low-value or poorly studied bronchiolitis interventions among health care personnel, with RNs/RTs generally perceiving higher benefit. Deimplementation, educational, and quality improvement efforts should be designed with an interprofessional framework., (Copyright © 2023 by the American Academy of Pediatrics.)

Objective: There is a lack of data about the clinicopathological and molecular characteristics of de novo versus secondary dedifferentiated chordoma (DC). This integrated study aimed to investigate the similarities and differences in clinicopathological manifestations, prognoses, and molecular profiles of these 2 subtypes., Methods: We accessed the Surveillance, Epidemiology, and End Results (SEER) Program for DC cases from 1975 to 2020. Three electronic databases were also searched for additional DCs. Individual patient data of DC patients from SEER and published literature were combined in integrated analyses., Results: After excluding duplicated patients, we identified 14 and 116 DC patients from SEER and published literature, respectively. There were 74 de novo, 39 secondary, and 18 cases with unknown origin. Our results showed that de novo and secondary DCs were not statistically different in terms of age, gender, primary location, tumor size, distant metastasis at diagnosis, extent of resection, and chemotherapy receipt. There was limited available molecular data for de novo and secondary DCs, though examples TP53 mutations were found in both. In addition, the rates of tumor relapse, metastasis during follow-up, and patient mortality were also comparable between the 2 groups. In the multivariate Cox regression model, we demonstrated that gross total removal and radiotherapy use were associated with prolonged survival of DCs., Conclusions: De novo and secondary DCs were statistically comparable in terms of patient demographics, clinical manifestations, and prognoses. Gross total excision and radiotherapy were optimal treatments associated with better outcomes of DC patients., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: Conventional coagulation tests (CCTs) cannot identify hypercoagulation, despite being common in patients with sepsis. Moreover, CCTs overdiagnose hypocoagulation, which increases unnecessary blood transfusion. Therefore, we aimed to use rotational thromboelastometry (ROTEM) to classify the coagulation status of patients with sepsis with abnormal CCTs and to identify the main coagulation components that affect coagulation status., Patients and Methods: This study was part of an observational study to investigate ROTEM use in 161 patients with sepsis with the Sepsis-3 criteria. They underwent concurrent CCTs and ROTEM assessments within 24 hours of Intensive Care Unit admission at the University Medical Center, Ho Chi Minh City, from June 2020 to December 2021. This study only extracted data from patients with sepsis with abnormal CCTs, including activated partial thromboplastin time ratio, international normalized ratio (INR), platelet count, and fibrinogen concentration., Results: A total of 158 patients with sepsis with abnormal CCTs had a median age of 69, and 48.7% were women. Of 34 patients with INR ≥1.6, ROTEM identified 11.8% with hypercoagulation and 20.6% with normal coagulation. Of 29 patients with platelet counts <100 (103/mm3), ROTEM identified 3.5% with hypercoagulation and 24.1% with normal coagulation. In the ROTEM-based hypercoagulability group, an increase in maximum clot firmness was observed in 95.1% of cases; also, this group had significantly higher plasma fibrinogen concentrations than other groups (p<0.005)., Conclusions: ROTEM can reveal hypercoagulability in patients with sepsis with hypocoagulation based on CCTs. Hyperfibrinogenemia causes hypercoagulation in patients with sepsis.

The pathology of asthma is characterized by marked day-night variation, which is likely controlled by circadian clock activity. This study aimed to clarify the association of core circadian clock gene expression with clinical features of asthma. For this purpose, we accessed the National Center for Biotechnology Information database and analyzed transcriptomes of peripheral blood mononuclear cells and clinical characteristics of 134 pediatric/adolescent patients with asthma. Based on the expression patterns of seven core circadian clock genes ( CLOCK, BMAL1, PER1-3, CRY1-2 ), we identified three circadian clusters (CCs) with distinct comorbidities and transcriptomic expressions. In the three CC subtypes, allergic rhinitis, and atopic dermatitis, both asthma comorbidities occurred in different proportions: CC1 had a high proportion of allergic rhinitis and atopic dermatitis; CC2 had a high proportion of atopic dermatitis but a low proportion of allergic rhinitis; and CC3 had a high proportion of allergic rhinitis but a low proportion of atopic dermatitis. This might be associated with the low activity of the FcεRI signaling pathway in CC2 and the cytokine-cytokine receptor interaction pathways in CC3. This is the first report to consider circadian clock gene expression in subcategories of patients with asthma and to explore their contribution to pathophysiology and comorbidity.

This study aimed to reveal the prognostic role of the Hippo pathway in different histopathological subtypes of renal cell carcinoma (RCC). The TCGA-KIRC (n = 537), TCGA-KIRP (n = 291) and TCGA-KICH (n = 113), which contain data about clear cell (ccRCC), papillary (pRCC) and chromophobe RCC (chRCC), respectively, were investigated. Gene Set Variation Analysis was used to compare the activity of many pathways within a single sample. Oncogenic pathway-related expression differed between cases of ccRCC involving low and high Hippo pathway activity. There were two subsets of ccRCC, in which the cancer exhibited lower and higher Hippo signalling activity, respectively, compared with normal tissue. In the ccRCC cohort, lower Hippo pathway activity was associated with a higher clinical stage (p < 0.001). The Hippo pathway (HR = 0.29; 95% CI = 0.17-0.50, p < 0.001), apoptosis (HR = 6.02; 95% CI = 1.47-24.61; p = 0.013) and the p53 pathway (HR = 0.09; 95% CI = 0.02-0.36; p < 0.001) were identified as independent prognostic factors for ccRCC. The 5-year overall survival of the ccRCC patients with low and high Hippo pathway activity were 51.9% (95% CI = 45.0-59.9) and 73.6% (95% CI = 67.8-79.9), respectively. In conclusion, the Hippo pathway plays an important role in the progression of ccRCC. Low Hippo pathway activity is associated with poor outcomes in ccRCC, indicating the tumour suppressor function of this pathway., (© 2022 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

Purpose: Tumor-stroma ratio (TSR) of invasive breast carcinoma has gained attention in recent years due to its prognostic significance. Previous studies showed TSR is a potential biomarker for indicating the tumor response to neoadjuvant chemotherapy. However, it is not clear how well TSR evaluation in biopsy specimens might reflect the TSR in resection specimens. We conducted a study to investigate whether biopsy evaluation of TSR can be an alternative method., Method: We collected cases with invasive breast carcinoma of no special type (IBC-NST) from University of Yamanashi hospital between 2011 and 2017 whose biopsy and resection specimens both had a pathologically diagnosis of IBC-NST (n = 146). We conceptualized a method for evaluating TSR in biopsy specimens within a preliminary cohort (n = 50). Within the studied cohort (n = 96), biopsy-based TSR (b-TSR) and resection-based TSR (r-TSR) were scored by two pathologists. We then evaluated our method's validity and performance by measuring interobserver variability between the two pathologists, Spearman's correlation between b-TSR and r-TSR, and the receiver operating characteristics (ROC) analysis for defining stroma-rich and stroma-poor tumors., Results: Intra-class coefficient between the two pathologists was 0.59. The correlation coefficients between b-TSR and r-TSR in the two pathologists were 0.45 and 0.37. The ROC areas under the curve were 0.7 and 0.67. By considering an r-TSR of < 50% as stroma-rich, the sensitivity and specificity of detecting stroma-rich tumors were 64.1% and 66.7%, respectively, when b-TSR was < 40%., Conclusion: Our current b-TSR evaluation method can provide information about r-TSR and facilitate pre-treatment therapy follow-up., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

This study focuses on the effects of the chemical process and heating time at 900 °C on pristine anthracite coal (provided by Vang Danh coal, Quang Ninh province, Vietnam) and explores its structure and electrochemical performance when used as an anode in Na-ion batteries. After chemical treatment with NaOH and H 2 SO 4 , the impurity content in the raw material decreased significantly ( e.g. , ash content dropped from 4.4% to 0.9%, etc. ). The interspacing between the graphene layers in the anthracite structure also increased after the heat treatment. Besides, on extending the heating time, the anthracite structure became more disordered than the samples heated for shorter times. Therefore, the intercalation ability of Na + ions in the anthracite structure increased, and the sample heated at 900 °C for 6 hours exhibited the highest reversible capacity of up to 160 mA h g -1 with adequate capacity retention after 100 cycles at C/10 rate., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

The risk of distant metastasis in medullary thyroid carcinoma (MTC) has not been well studied. Additional evaluation of MTC metastatic risk can be helpful for improving the quality of medical management. Therefore, we conducted a large population study to develop a method to stratify the risk of metastasis at the initial presentation of MTC patients. We collected 3612 MTC patients from the Surveillance, Epidemiology, and End Results (SEER) database, and included 2526 MTC patients in the study after applying exclusion criteria. We selected the most informative variables from a learning cohort of 2019 patients to obtain 1000 models by repetitive random data splicing into training and regularization cohorts. We selected the optimal model and developed a risk table from that model. Our risk table variables consist of age, gender, tumor size, extrathyroidal extension, and lymph node metastasis. The final model showed good calibration when metastatic risk was < 25% and good performance with areas under the curve (AUCs) of 0.81, 0.84, and 0.84 in the training, regularization, and test cohorts, respectively. We performed K-means clustering analysis on the model's metastatic estimation and determined three risk groups of patients with significant survival differences (p < 0.001). Low-risk patients had 0.88%, 1.3%, and 0.5% while high-risk patients had 19.7%, 15.8%, and 17.8% risk of metastasis in the three cohorts, respectively. The incorporation of our table into the International MTC Grading System (IMTCGS) requires more comprehensive clinicopathological studies., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Pleomorphic sarcoma of soft tissue 1 (PSST) is a heterogeneous group of sarcomas with different prognoses. Survival patterns of this tumor group have not been thoroughly investigated. Prognostic models should be developed to support individualized evaluation of PSST patients., Materials and Methods: We collected cases of soft tissue tumors in the Surveillance, Epidemiology, and End Results 2 (SEER) database, excluding tumors located in intra-abdominal and retroperitoneal regions. We included patients with histopathologic diagnoses of tumors in the PSST group (n = 14,685) and compared the survival patterns of the different histologic types. To develop a prognostic model of leiomyosarcoma, we divided leiomyosarcoma patients into two groups. The first group (n = 4136) was patients with missing values, which became our training cohort after imputation. The second group (n = 671) was the validation cohort., Results: Leiomyosarcoma was the most common PSST (32.7 %). By pairwise comparison, we found that histologic types of PSST can be divided into 4 prognostic groups (p < 0.001). Regarding our model, the C-index, K statistic, and explained variation R 2 D were 0.84, 0.8, 0.52 (training cohort) and 0.76, 0.76, 0.4 (validation cohort), respectively., Conclusions: We found that the survival patterns of PSST can be divided into four distinct groups of histology types. Our dynamic nomogram can individualize the management of leiomyosarcoma patients and, therefore, can be very helpful for clinician-patient communication due to its applicability of flexibility., Competing Interests: Declare of interest None., (Copyright © 2022. Published by Elsevier GmbH.)

Background: Hyperglycemia is commonly seen in critically ill patients. This disorder was also seen in coronavirus disease 2019 (COVID-19) patients and was associated with a worse prognosis. The current study determined the prevalence, risk factors, and prognostic implications of hyperglycemia in COVID-19 patients., Method: This was a retrospective observational study performed in an intensive care unit for COVID-19 patients. Electronic data of COVID-19 patients admitted to the intensive care unit from August 2nd to October 15th, 2021, were collected. Patients were divided into non-hyperglycemia, hyperglycemia in diabetic patients, and hyperglycemia in non-diabetic patients. Primary outcomes were 28-day and in-hospital mortalities. Multinomial logistic regression and multivariable Cox regression models were used to determine the risk factors for hyperglycemia and mortality, respectively., Results: Hyperglycemia was documented in 65.6% of patients: diabetic patients (44.8%) and new-onset hyperglycemia (20.8%). In-hospital and 28-day mortality rates were 30.2% and 26.1%, respectively. Respiratory failure, corticosteroid therapy, and a higher level of procalcitonin were risk factors for hyperglycemia in diabetic patients, whereas cardiovascular diseases, respiratory failure, and higher aspartate aminotransferase/glutamate aminotransferase ratio were risk factors for hyperglycemia in non-diabetic patients. The risk of the 28-day mortality rate was highest in the new-onset hyperglycemia (hazard ratio [HR] 3.535, 95% confidence interval [CI] 1.338-9.338, p=0.011), which was higher than hyperglycemia in type 2 diabetes mellitus patients (HR 1.408, 95% CI 0.513-3.862, p=0.506)., Conclusion: Hyperglycemia was common in COVID-19 patients in the intensive care unit. Hyperglycemia reflected the disease severity but was also secondary to therapeutic intervention. New-onset hyperglycemia was associated with poorer outcomes than that in diabetic patients., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Le et al.)

Objective: DICER1-mutant malignant brain neoplasms are very rare tumors, and published data have relied on case reports or small case series. In this review, the authors aimed to systematically summarize the types and distribution patterns of DICER1 mutations, clinicopathological characteristics, and prognostic outcomes of these tumors., Methods: The authors searched PubMed and Web of Science for relevant studies. They included studies if they provided individual patient data of primary malignant brain tumors carrying DICER1 mutations., Results: The authors found 16 studies consisting of 9 embryonal tumors with multilayered rosettes (ETMRs), 30 pineoblastomas, 52 primary intracranial sarcomas, and 27 pituitary blastomas. Pineoblastoma, ETMR, and pituitary blastoma were more likely to carry DICER1 germline mutations, while only a small subset of primary intracranial sarcomas harbored these mutations (p < 0.001). Nearly 80% of tumors with germline mutations also had another somatic mutation in DICER1. ETMR and primary intracranial sarcoma were associated with an increased risk for tumor progression and relapse compared with pituitary blastoma and pineoblastoma (p = 0.0025), but overall survival (OS) was not significantly different. Gross-total resection (GTR) and radiotherapy administration were associated with prolonged OS., Conclusions: ETMR, pineoblastoma, primary intracranial sarcoma, and pituitary blastoma should be considered rare phenotypes of the DICER1 syndrome, and families should be counseled and screened for associated tumors. ETMR and primary intracranial sarcoma had a higher risk of relapse. GTR and radiotherapy appeared to improve the OS of patients with DICER1-mutant malignant intracranial tumors.