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1.
Int J Older People Nurs ; 19(5): e12647, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39277879

ABSTRACT

BACKGROUND: Due to rapid increases in the number of Korean people with dementia, dementia has become a priority health issue in South Korea. Likewise, the well-being of family caregivers of people with dementia has also become an issue of concern. However, little is known about the resilience of Korean family caregivers because there is a lack of review studies from a Korean cultural perspective about the resilience of family caregivers of people with dementia. OBJECTIVES: The purpose of this scoping review was to investigate quantitative studies related to resilience theories, measurement instruments, correlates and resilience interventions for family caregivers of people with dementia. METHOD: This review was conducted according to the Joanna Briggs Institute based on Arksey and O'Malley. Nine databases were searched to retrieve evidence published in English or Korean between January 2000 and September 2022. Studies with a quantitative research design reporting the resilience of family caregivers of people with dementia based on a resilience theory framework were included. RESULTS: A total of 13 studies were included in this review. All studies used either a modified McCubbin and McCubbin's family stress, adjustment and adaptation model or Walsh's family resilience model. All resilience instruments were used without cross-cultural adaptation. Family adaptation, social support, life satisfaction, family (di)stress and caregiver burden were associated with resilience among family caregivers. A few family resilience-enhancing programmes showed a positive effect on caregiver resilience. CONCLUSION: This review noted that all the resilience measures documented in this study need to test for cultural adaptation in a Korean context. Further research is required to develop and implement family-based, culturally tailored interventions to effectively enhance Korean resilience for family caregivers of people with dementia. IMPLICATIONS FOR PRACTICE: Gerontological nurses should include Korean family caregivers in their nursing care and assess whether family caregivers have depression or suicidal thoughts to promote better health outcomes for caregivers and their family members.


Subject(s)
Caregivers , Dementia , Resilience, Psychological , Humans , Caregivers/psychology , Dementia/nursing , Dementia/ethnology , Republic of Korea/ethnology , Adaptation, Psychological , Social Support , Family/psychology
2.
J Pathol Transl Med ; 2024 Sep 12.
Article in English | MEDLINE | ID: mdl-39257049

ABSTRACT

Background: Papillary renal cell carcinoma (pRCC) is the second most common histological subtype of renal cell carcinoma and is considered a morphologically and molecularly heterogeneous tumor. Accurate classification and assessment of the immunohistochemical features of possible therapeutic targets are needed for precise patient care. We aimed to evaluate immunohistochemical features and possible therapeutic targets of papillary renal neoplasms. Methods: We collected 140 papillary renal neoplasms from three different hospitals and conducted immunohistochemical studies on tissue microarray slides. We performed succinate dehydrogenase B, fumarate hydratase, and transcription factor E3 immunohistochemical studies for differential diagnosis and re-classified five cases (3.6%) of papillary renal neoplasms. In addition, we conducted c-MET, p16, c-Myc, Ki-67, p53, and stimulator of interferon genes (STING) immunohistochemical studies to evaluate their pathogenesis and value for therapeutic targets. Results: We found that c-MET expression was more common in pRCC (classic) (p = .021) among papillary renal neoplasms and Ki-67 proliferation index was higher in pRCC (not otherwise specified, NOS) compared to that of pRCC (classic) and papillary neoplasm with reverse polarity (marginal significance, p = .080). Small subsets of cases with p16 block positivity (4.5%) (pRCC [NOS] only) and c-Myc expression (7.1%) (pRCC [classic] only) were found. Also, there were some cases showing STING expression and those cases were associated with increased Ki-67 proliferation index (marginal significance, p = .063). Conclusions: Our findings suggested that there are subsets of pRCC with c-MET, p16, c-MYC, and STING expression and those cases could be potential candidates for targeted therapy.

3.
Healthcare (Basel) ; 12(9)2024 Apr 29.
Article in English | MEDLINE | ID: mdl-38727475

ABSTRACT

We established a protocol for the traditional Korean medicine examination (KME) and methodically gathered data following this protocol. Potential indicators for KME were extracted through a literature review; the first KME protocol was developed based on three rounds of expert opinions. The first KME protocol's feasibility was confirmed, and data were collected over four years from traditional Korean medicine (KM) hospitals, focusing on healthy adults, using the final KME protocol. A literature review identified 175 potential core indicators, condensed into 73 indicators after three rounds of expert consultation. The first KME protocol, which was categorized under questionnaires and medical examinations, was developed after the third round of expert opinions. A pilot study using the first KME protocol was conducted to ensure its validity, leading to modifications resulting in the development of the final KME protocol. Over four years, data were collected from six KM hospitals, focusing on healthy adults; we obtained a dataset comprising 11,036 healthy adults. This is the first protocol incorporating core indicators of KME in a quantitative form and systematically collecting data. Our protocol holds potential merit in evaluating predisposition to diseases or predicting diseases.

4.
Medicine (Baltimore) ; 103(21): e38293, 2024 May 24.
Article in English | MEDLINE | ID: mdl-38787987

ABSTRACT

Metabolic rate has been used in thermophysiological models for predicting the thermal response of humans. However, only a few studies have investigated the association between an individual's trait-like thermal sensitivity and resting energy expenditure (REE), which resulted in inconsistent results. This study aimed to explore the association between REE and perceived thermal sensitivity. The REE of healthy adults was measured using an indirect calorimeter, and perceived thermal intolerance and sensation in the body were evaluated using a self-administered questionnaire. In total, 1567 individuals were included in the analysis (women = 68.9%, age = 41.1 ±â€…13.2 years, body mass index = 23.3 ±â€…3.3 kg/m2, REE = 1532.1 ±â€…362.4 kcal/d). More women had high cold intolerance (31.8%) than men (12.7%), and more men had high heat intolerance (23.6%) than women (16.1%). In contrast, more women experienced both cold (53.8%) and heat (40.6%) sensations in the body than men (cold, 29.1%; heat, 27.9%). After adjusting for age, fat-free mass, and fat mass, lower cold intolerance, higher heat intolerance, and heat sensation were associated with increased REE only in men (cold intolerance, P for trend = .001; heat intolerance, P for trend = .037; heat sensation, P = .046), whereas cold sensation was associated with decreased REE only in women (P = .023). These findings suggest a link between the perceived thermal sensitivity and REE levels in healthy individuals.


Subject(s)
Calorimetry, Indirect , Energy Metabolism , Humans , Female , Male , Adult , Cross-Sectional Studies , Middle Aged , Energy Metabolism/physiology , Thermosensing/physiology , Basal Metabolism/physiology , Sex Factors , Hot Temperature/adverse effects , Cold Temperature , Body Mass Index
5.
Heliyon ; 10(7): e28464, 2024 Apr 15.
Article in English | MEDLINE | ID: mdl-38571591

ABSTRACT

Metschnikowia persimmonesis, a novel endophytic yeast strain isolated from Diospyros kaki calyx, possesses strong antimicrobial activity. We investigated its potential use as an environmentally safe food biocontrol agent through genomics, transcriptomics, and metabolomics. Secondary metabolites were isolated from M. persimmonesis, followed by chemical structure elucidation, PUL gene cluster identification, and RNA sequencing. Pulcherrimin was isolated using 2 M NaOH, its structure was confirmed, and the yield was quantified. Biocontrol efficacy of M. persimmonesis on persimmon fruits and calyx was evaluated by assessing lesion diameter and disease incidence. Following compounds were isolated from M. persimmonesis co-culture with Botrytis cinerea and Fusarium oxysporum: fusaric acid, benzoic acid, benzeneacetic acid, 4-hydroxybenzeneacetic acid, 4-(-2-hydoxyethyl)-benzoic acid, cyclo (Leu-Leu), benzenemethanol, 4-hydroxy-benzaldehide, 2-hydroxy-4-methoxy-benzoic acid, 4-hydroxy-benzoic acid, lumichrome, heptadecanoic acid, and nonadecanoic acid. Exposing M. persimmonesis to different growth media conditions (with or without sugar) resulted in the isolation of five compounds: Tyrosol, Cyclo (Pro-Val), cyclo(L-Pro-L-Tyr), cyclo(Leu-Leu), and cyclo(l-tyrosilylicine). Differentially expressed gene analysis revealed 3264 genes that were significantly expressed (fold change ≥2 and p-value ≤0.05) during M. persimmonesis growth in different media, of which only 270 (8.27%) showed altered expression in all sample combinations with Luria-Bertani Agar as control. Minimal media with ferric ions and tween-80 triggered the most gene expression changes, with the highest levels of PUL gene expression and pulcherrimin yield (262.166 mg/L) among all media treatments. M. persimmonesis also produced a higher amount of pulcherrimin (209.733 mg/L) than Metschnikowia pulcherrima (152.8 mg/L). M. persimmonesis inhibited the growth of Fusarium oxysporum in persimmon fruit and calyx. Toxicity evaluation of M. persimmonesis extracts showed no harmful effects on the liver and mitochondria of zebrafish, and no potential risk of cardiotoxicity in hERG-HEK293 cell lines. Thus, M. persimmonesis can be commercialized as a potent and safe biocontrol agent for preserving food products.

6.
Histopathology ; 85(1): 81-91, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38477366

ABSTRACT

AIMS: Immune checkpoint inhibitors targeting programmed death-ligand 1 (PD-L1) have shown promising clinical outcomes in urothelial carcinoma (UC). The combined positive score (CPS) quantifies PD-L1 22C3 expression in UC, but it can vary between pathologists due to the consideration of both immune and tumour cell positivity. METHODS AND RESULTS: An artificial intelligence (AI)-powered PD-L1 CPS analyser was developed using 1,275,907 cells and 6175.42 mm2 of tissue annotated by pathologists, extracted from 400 PD-L1 22C3-stained whole slide images of UC. We validated the AI model on 543 UC PD-L1 22C3 cases collected from three institutions. There were 446 cases (82.1%) where the CPS results (CPS ≥10 or <10) were in complete agreement between three pathologists, and 486 cases (89.5%) where the AI-powered CPS results matched the consensus of two or more pathologists. In the pathologist's assessment of the CPS, statistically significant differences were noted depending on the source hospital (P = 0.003). Three pathologists reevaluated discrepancy cases with AI-powered CPS results. After using the AI as a guide and revising, the complete agreement increased to 93.9%. The AI model contributed to improving the concordance between pathologists across various factors including hospital, specimen type, pathologic T stage, histologic subtypes, and dominant PD-L1-positive cell type. In the revised results, the evaluation discordance among slides from different hospitals was mitigated. CONCLUSION: This study suggests that AI models can help pathologists to reduce discrepancies between pathologists in quantifying immunohistochemistry including PD-L1 22C3 CPS, especially when evaluating data from different institutions, such as in a telepathology setting.


Subject(s)
Artificial Intelligence , B7-H1 Antigen , Carcinoma, Transitional Cell , Observer Variation , Urinary Bladder Neoplasms , Humans , B7-H1 Antigen/analysis , B7-H1 Antigen/metabolism , Urinary Bladder Neoplasms/pathology , Urinary Bladder Neoplasms/diagnosis , Urinary Bladder Neoplasms/metabolism , Carcinoma, Transitional Cell/pathology , Carcinoma, Transitional Cell/metabolism , Carcinoma, Transitional Cell/diagnosis , Biomarkers, Tumor/analysis , Biomarkers, Tumor/metabolism , Urologic Neoplasms/pathology , Urologic Neoplasms/diagnosis , Male , Immunohistochemistry/methods , Female , Aged
8.
Proc Natl Acad Sci U S A ; 121(4): e2308960121, 2024 Jan 23.
Article in English | MEDLINE | ID: mdl-38232288

ABSTRACT

Metabolic disorders are characterized by an imbalance in muscle fiber composition, and a potential therapeutic approach involves increasing the proportion of oxidative muscle fibers. Prokineticin receptor 1 (PROKR1) is a G protein-coupled receptor that plays a role in various metabolic functions, but its specific involvement in oxidative fiber specification is not fully understood. Here, we investigated the functions of PROKR1 in muscle development to address metabolic disorders and muscular diseases. A meta-analysis revealed that the activation of PROKR1 upregulated exercise-responsive genes, particularly nuclear receptor subfamily 4 group A member 2 (NR4A2). Further investigations using ChIP-PCR, luciferase assays, and pharmacological interventions demonstrated that PROKR1 signaling enhanced NR4A2 expression by Gs-mediated phosphorylation of cyclic adenosine monophosphate (cAMP) response element-binding protein (CREB) in both mouse and human myotubes. Genetic and pharmacological interventions showed that the PROKR1-NR4A2 axis promotes the specification of oxidative muscle fibers in both myocytes by promoting mitochondrial biogenesis and metabolic function. Prokr1-deficient mice displayed unfavorable metabolic phenotypes, such as lower lean mass, enlarged muscle fibers, impaired glucose, and insulin tolerance. These mice also exhibited reduced energy expenditure and exercise performance. The deletion of Prokr1 resulted in decreased oxidative muscle fiber composition and reduced activity in the Prokr1-CREB-Nr4a2 pathway, which were restored by AAV-mediated Prokr1 rescue. In summary, our findings highlight the activation of the PROKR1-CREB-NR4A2 axis as a mechanism for increasing the oxidative muscle fiber composition, which positively impacts overall metabolic function. This study lays an important scientific foundation for the development of effective muscular-metabolic therapeutics with unique mechanisms of action.


Subject(s)
Gene Expression Regulation , Metabolic Diseases , Mice , Animals , Humans , Signal Transduction , Muscle Fibers, Skeletal/metabolism , Oxidative Stress , Metabolic Diseases/metabolism , Nuclear Receptor Subfamily 4, Group A, Member 2/metabolism
9.
Cancer Res Treat ; 56(1): 280-293, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37697729

ABSTRACT

PURPOSE: This study aimed to evaluate the molecular features of clear cell adenocarcinoma (CCA) of the urinary tract and investigate its pathogenic pathways and possible actionable targets. MATERIALS AND METHODS: We retrospectively collected the data of patients with CCA between January 1999 and December 2016; the data were independently reviewed by two pathologists. We selected five cases of urinary CCA, based on the clinicopathological features. We analyzed these five cases by whole exome sequencing (WES) and subsequent bioinformatics analyses to determine the mutational spectrum and possible pathogenic pathways. RESULTS: All patients were female with a median age of 62 years. All tumors were located in the urethra and showed aggressive behavior with disease progression. WES revealed several genetic alterations, including driver gene mutations (AMER1, ARID1A, CHD4, KMT2D, KRAS, PBRM1, and PIK3R1) and mutations in other important genes with tumor-suppressive and oncogenic roles (CSMD3, KEAP1, SMARCA4, and CACNA1D). We suggest putative pathogenic pathways (chromatin remodeling pathway, mitogen-activated protein kinase signaling pathway, phosphoinositide 3-kinase/AKT/mammalian target of rapamycin pathway, and Wnt/ß-catenin pathway) as candidates for targeted therapies. CONCLUSION: Our findings shed light on the molecular background of this extremely rare tumor with poor prognosis and can help improve treatment options.


Subject(s)
Adenocarcinoma, Clear Cell , Humans , Female , Middle Aged , Male , Adenocarcinoma, Clear Cell/genetics , Adenocarcinoma, Clear Cell/pathology , Kelch-Like ECH-Associated Protein 1/genetics , Urethra/pathology , Phosphatidylinositol 3-Kinases , Retrospective Studies , NF-E2-Related Factor 2/genetics , Mutation , DNA Helicases/genetics , Nuclear Proteins/genetics , Transcription Factors/genetics
10.
J Invest Dermatol ; 144(3): 633-644, 2024 Mar.
Article in English | MEDLINE | ID: mdl-37838329

ABSTRACT

Fibrotic diseases are characterized by the abnormal accumulation of collagen in the extracellular matrix, leading to the functional impairment of various organs. In the skin, excessive collagen deposition manifests as hypertrophic scars and keloids, placing a substantial burden on patients and the healthcare system worldwide. HSP47 is essential for proper collagen assembly and contributes to fibrosis. However, identifying clinically applicable HSP47 inhibitors has been a major pharmaceutical challenge. In this study, we identified benzbromarone (BBR) as an HSP47 inhibitor for hypertrophic scarring treatment. BBR inhibited collagen production and secretion in fibroblasts from patients with keloid by binding to HSP47 and inhibiting the interaction between HSP47 and collagen. Interestingly, BBR not only inhibits HSP47 but also acts as a molecular glue degrader that promotes its proteasome-dependent degradation. Through these molecular mechanisms, BBR effectively reduced hypertrophic scarring in mini pigs and rats with burns and/or excisional skin damage. Thus, these findings suggest that BBR can be used to clinically treat hypertrophic scars and, more generally, fibrotic diseases.


Subject(s)
Cicatrix, Hypertrophic , Keloid , Humans , Animals , Rats , Swine , Cicatrix, Hypertrophic/pathology , Benzbromarone/metabolism , Benzbromarone/pharmacology , HSP47 Heat-Shock Proteins/metabolism , Swine, Miniature/metabolism , Keloid/pathology , Collagen/metabolism , Fibrosis , Fibroblasts/metabolism
12.
Medicine (Baltimore) ; 102(39): e35039, 2023 Sep 29.
Article in English | MEDLINE | ID: mdl-37773806

ABSTRACT

This study is aimed to explore the performance of texture-based machine learning and image-based deep-learning for enhancing detection of Transitional-zone prostate cancer (TZPCa) in the background of benign prostatic hyperplasia (BPH), using a one-to-one correlation between prostatectomy-based pathologically proven lesion and MRI. Seventy patients confirmed as TZPCa and twenty-nine patients confirmed as BPH without TZPCa by radical prostatectomy. For texture analysis, a radiologist drew the region of interest (ROI) for the pathologically correlated TZPCa and the surrounding BPH on T2WI. Significant features were selected using Least Absolute Shrinkage and Selection Operator (LASSO), trained by 3 types of machine learning algorithms (logistic regression [LR], support vector machine [SVM], and random forest [RF]) and validated by the leave-one-out method. For image-based machine learning, both TZPCa and BPH without TZPCa images were trained using convolutional neural network (CNN) and underwent 10-fold cross validation. Sensitivity, specificity, positive and negative predictive values were presented for each method. The diagnostic performances presented and compared using an ROC curve and AUC value. All the 3 Texture-based machine learning algorithms showed similar AUC (0.854-0.861)among them with generally high specificity (0.710-0.775). The Image-based deep learning showed high sensitivity (0.946) with good AUC (0.802) and moderate specificity (0.643). Texture -based machine learning can be expected to serve as a support tool for diagnosis of human-suspected TZ lesions with high AUC values. Image-based deep learning could serve as a screening tool for detecting suspicious TZ lesions in the context of clinically suspected TZPCa, on the basis of the high sensitivity.


Subject(s)
Deep Learning , Prostatic Hyperplasia , Prostatic Neoplasms , Male , Humans , Prostatic Hyperplasia/diagnostic imaging , Retrospective Studies , Prostatic Neoplasms/diagnostic imaging , Prostatic Neoplasms/surgery , Prostatic Neoplasms/pathology , Machine Learning
13.
Gynecol Oncol ; 177: 117-124, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37660413

ABSTRACT

OBJECTIVE: In 2014, the World Health Organization introduced a new histologic classification by dividing primary mucinous ovarian carcinoma (PMOC) into two: expansile (ES) or infiltrative subtypes (IS). This study investigated the clinical implications of these histological subtypes on survival outcomes. METHODS: Data from 131 patients with PMOC who underwent primary surgery between 2003 and 2021 were analyzed. The patients baseline characteristics, surgical and pathological information were collected. Survival outcomes were calculated, while factors affecting them were also investigated. RESULTS: During 55.9 months of median follow-up, 27 (20.6%) patients experienced recurrence and 20 (15.3%) died. Among 131 patients, 113 patients were classified into 87 (77%) ES and 26 (23%) IS after a slide review. Advanced stage, lymph node involvement, and residual tumors after surgery were more common in the IS, showing poorer prognosis. In multivariate analyses, advanced stage and residual tumors after surgery were associated with worse survival, while the IS showed no statistical significance. In subgroup analysis for stage I disease, survival did not vary between subtypes. Nevertheless, patients in the IS group who underwent fertility-sparing surgeries demonstrated a 5-year progression-free survival (PFS) rate of 83.3%, significantly lower than patients without fertility preservation, irrespective of histologic subtypes (5-year PFS rate: 97.9%; P = 0.002 for the ES, 5-year PFS rate: 100%; P = 0.001 for the IS). CONCLUSIONS: The IS of PMOC had poorer survival outcomes and a higher proportion of advanced-stage tumors. Although its independent prognostic significance remains uncertain, adjuvant chemotherapy should be considered for patients with fertility preservation in the IS group.

14.
J Breast Cancer ; 26(5): 479-491, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37704381

ABSTRACT

PURPOSE: In this study, we investigated the prognostic implications of focal breast edema on preoperative breast magnetic resonance imaging (MRI) in patients with breast cancer. METHODS: Data of 899 patients with breast cancer at a single institution were retrospectively analyzed. The patients were divided into an edema-positive group (EPG) and an edema-negative group (ENG) based on the presence of peritumoral, prepectoral, or subcutaneous edema. Two radiologists evaluated the presence or absence of focal edema and its subtypes on preoperative breast MRI. Clinicopathologic characteristics and survival outcomes were compared between the two groups and among the three subtypes using Pearson's χ² test, Kaplan-Meier estimator, and Cox proportional hazards model. RESULTS: There were 399 (44.4%) and 500 (55.6%) patients in the EPG and ENG, respectively. The EPG showed significantly higher rates of axillary lymph node metastasis (55.6% vs. 19.2%, p < 0.001) and lymphovascular invasion (LVI) (57.9% vs. 12.6%, p < 0.001) than the ENG. Patients in the EPG showed significantly worse overall survival (OS) rate (log-rank p < 0.001; hazard ratio [HR], 4.83; 95% confidence interval [CI], 2.56-9.11) and recurrence-free survival rate (log-rank p < 0.001; HR, 3.00; 95% CI, 1.94-4.63) than those in the ENG. After adjusting for other variables, focal breast edema remained a significant factor affecting the OS rate, regardless of the edema type. Specifically, the presence of subcutaneous edema emerged as the strongest predictor for OS with the highest HR (p < 0.001; HR, 9.10; 95% CI, 3.05-27.15). CONCLUSION: Focal breast edema on preoperative breast MRI implies a higher possibility of LVI and axillary lymph node metastasis, which can lead to a poor prognosis. A detailed description of focal breast edema, especially subcutaneous edema, on preoperative breast MRI may provide prognostic predictions. More intensive surveillance is required for patients with breast cancer and focal preoperative breast edema.

15.
Med Image Anal ; 89: 102886, 2023 10.
Article in English | MEDLINE | ID: mdl-37494811

ABSTRACT

Microsatellite instability (MSI) refers to alterations in the length of simple repetitive genomic sequences. MSI status serves as a prognostic and predictive factor in colorectal cancer. The MSI-high status is a good prognostic factor in stage II/III cancer, and predicts a lack of benefit to adjuvant fluorouracil chemotherapy in stage II cancer but a good response to immunotherapy in stage IV cancer. Therefore, determining MSI status in patients with colorectal cancer is important for identifying the appropriate treatment protocol. In the Pathology Artificial Intelligence Platform (PAIP) 2020 challenge, artificial intelligence researchers were invited to predict MSI status based on colorectal cancer slide images. Participants were required to perform two tasks. The primary task was to classify a given slide image as belonging to either the MSI-high or the microsatellite-stable group. The second task was tumor area segmentation to avoid ties with the main task. A total of 210 of the 495 participants enrolled in the challenge downloaded the images, and 23 teams submitted their final results. Seven teams from the top 10 participants agreed to disclose their algorithms, most of which were convolutional neural network-based deep learning models, such as EfficientNet and UNet. The top-ranked system achieved the highest F1 score (0.9231). This paper summarizes the various methods used in the PAIP 2020 challenge. This paper supports the effectiveness of digital pathology for identifying the relationship between colorectal cancer and the MSI characteristics.


Subject(s)
Colorectal Neoplasms , Microsatellite Instability , Humans , Artificial Intelligence , Prognosis , Fluorouracil/therapeutic use , Colorectal Neoplasms/genetics , Colorectal Neoplasms/pathology
16.
Ultrasonography ; 42(3): 440-445, 2023 Jul.
Article in English | MEDLINE | ID: mdl-37337359

ABSTRACT

PURPOSE: This study was conducted to assess the role of renal Doppler ultrasonography (US) in predicting non-diabetic kidney disease (NDKD) in patients with diabetes, using histologic findings as the reference standard. METHODS: Fifty-nine consecutive patients with diabetes who underwent renal Doppler US and native kidney biopsy were included in this retrospective, single-institutional study. Based on histologic findings, patients were classified as having diabetic nephropathy (DN) or NDKD. Renal Doppler US findings, including cortical echogenicity, corticomedullary differentiation, and the resistive index (RI), were compared between DN and NDKD. A subgroup analysis according to chronic kidney disease (CKD) status was also performed. RESULTS: Cortical echogenicity and corticomedullary differentiation showed no significant differences between DN and NDKD (P=0.887 and P>0.99, respectively), whereas the RI was significantly higher in patients with DN than in those with NDKD (P=0.032). The subgroup analysis revealed a significant difference in the RI between DN and NDKD in patients with diabetes and CKD (P=0.010), but a significant difference was not found in those without CKD (P=0.713). When limited to patients with diabetes and CKD, the RI had an area under the curve value of 0.759, sensitivity of 57.1%, specificity of 81.0%, positive likelihood ratio of 3.0, and negative LR of 0.5 for predicting NDKD, using a cutoff value of ≤0.69. CONCLUSION: Renal Doppler US may be useful in predicting NDKD in patients with diabetes and CKD.

17.
Cancer Med ; 12(14): 15664-15675, 2023 07.
Article in English | MEDLINE | ID: mdl-37260182

ABSTRACT

PURPOSE: To explore genomic biomarkers in rectal cancer by performing whole-exome sequencing. MATERIALS AND METHODS: Pre-chemoradiation (CRT) biopsy and post-CRT surgical specimens were obtained from 27 patients undergoing neoadjuvant CRT followed by definitive resection. Exomes were sequenced to a mean coverage of 30×. Somatic single-nucleotide variants (SNVs) and insertions/deletions (indels) were identified. Tumor mutational burden was defined as the number of SNVs or indels. Mutational signatures were extracted and fitted to COSMIC reference signatures. Tumor heterogeneity was quantified with a mutant-allele tumor heterogeneity (MATH) score. Genetic biomarkers and frequently occurred copy number alterations (CNAs) were compared between pre- and post-CRT specimens. Their associations with tumor regression grade (TRG) and clinical outcomes were explored. RESULTS: Top five mutated genes were APC, TP53, NF1, KRAS, and NOTCH1 for pre-CRT samples and APC, TP53, NF1, CREBBP, and ATM for post-CRT samples. Several gene mutations including RUNX1, EGFR, and TP53 in pre-CRT samples showed significant association with clinical outcomes, but not with TRG. However, no such association was found in post-CRT samples. Discordance of driver mutation status was found between pre- and post-CRT samples. In tumor mutational burden analysis, higher number of SNVs or indels was associated with worse treatment outcomes. Six single-base substitution (SBS) signatures identified were SBS1, SBS30, SBS29, SBS49, SBS3, and SBS44. The MATH score decreased after CRT on paired analysis. Less than half of CNAs frequent in post-CRT samples were present in pre-CRT samples. CONCLUSION: Pre- and post-CRT samples showed different genomic landscape. Potential genetic biomarkers of pre-CRT samples found in the current analysis call for external validation.


Subject(s)
Adenocarcinoma , Rectal Neoplasms , Humans , Neoadjuvant Therapy , Rectal Neoplasms/genetics , Rectal Neoplasms/therapy , Rectal Neoplasms/pathology , Treatment Outcome , Biomarkers, Tumor/genetics , Genomics , Adenocarcinoma/genetics , Adenocarcinoma/therapy , Adenocarcinoma/pathology
19.
Aliment Pharmacol Ther ; 58(3): 322-333, 2023 08.
Article in English | MEDLINE | ID: mdl-37248793

ABSTRACT

BACKGROUND AND AIMS: Sarcopaenia is associated with advanced nonalcoholic fatty liver disease (NAFLD). However, the impact of the muscle mass categorised by muscle quality on fibrosis progression remains unclear. METHODS: A total of 292 patients with biopsy-proven NAFLD who underwent serial vibration-controlled transient elastography assessments at least 1 year from baseline were selected. The skeletal muscle area (SMA) was determined on abdominal computed tomography (CT) at the third lumbar vertebra level and categorised to normal-attenuation muscle area (NAMA), low-attenuation muscle area (LAMA) and intermuscular adipose tissue (IMAT) using a muscle quality map. These SMAs were normalised by the height squared to obtain the skeletal muscle index (SMI). RESULTS: At baseline, as the histological fibrosis stage increased, SMINAMA decreased and SMILAMA increased (p for trend = 0.014 and p for trend <0.001, respectively), which was not significant after adjustment for age, sex and obesity. During a median follow-up of 41 months, fibrosis progression was detected in 48 out of 292 patients, and higher SMILAMA quartiles independently increased the risk of fibrosis progression in a dose-dependent manner (hazard ratio [HR] per quartile: 1.41; 95% confidence interval [CI], 1.04-1.91). The highest quartile of SMILAMA increased the risk of fibrosis progression by 3.25 times compared to the lowest quartile of SMILAMA (95% CI, 1.18-8.90). SMINAMA quartiles were not associated with the risk of fibrosis progression. CONCLUSION: Increased low-quality muscle mass, but not decreased normal-quality muscle mass, as assessed by a muscle quality map in CT, predicts fibrosis progression in patients with NAFLD.


Subject(s)
Non-alcoholic Fatty Liver Disease , Humans , Non-alcoholic Fatty Liver Disease/pathology , Muscle, Skeletal/diagnostic imaging , Muscle, Skeletal/pathology , Liver Cirrhosis/diagnostic imaging , Liver Cirrhosis/complications , Obesity/complications , Biopsy
20.
Nano Converg ; 10(1): 19, 2023 Apr 28.
Article in English | MEDLINE | ID: mdl-37115353

ABSTRACT

Remote epitaxy, which was discovered and reported in 2017, has seen a surge of interest in recent years. Although the technology seemed to be difficult to reproduce by other labs at first, remote epitaxy has come a long way and many groups are able to consistently reproduce the results with a wide range of material systems including III-V, III-N, wide band-gap semiconductors, complex-oxides, and even elementary semiconductors such as Ge. As with any nascent technology, there are critical parameters which must be carefully studied and understood to allow wide-spread adoption of the new technology. For remote epitaxy, the critical parameters are the (1) quality of two-dimensional (2D) materials, (2) transfer or growth of 2D materials on the substrate, (3) epitaxial growth method and condition. In this review, we will give an in-depth overview of the different types of 2D materials used for remote epitaxy reported thus far, and the importance of the growth and transfer method used for the 2D materials. Then, we will introduce the various growth methods for remote epitaxy and highlight the important points in growth condition for each growth method that enables successful epitaxial growth on 2D-coated single-crystalline substrates. We hope this review will give a focused overview of the 2D-material and substrate interaction at the sample preparation stage for remote epitaxy and during growth, which have not been covered in any other review to date.

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