Origamic metal-organic framework toward mechanical metamaterial.

Origami, known as paper folding has become a fascinating research topic recently. Origami-inspired materials often establish mechanical properties that are difficult to achieve in conventional materials. However, the materials based on origami tessellation at the molecular level have been significantly underexplored. Herein, we report a two-dimensional (2D) porphyrinic metal-organic framework (MOF), self-assembled from Zn nodes and flexible porphyrin linkers, displaying folding motions based on origami tessellation. A combined experimental and theoretical investigation demonstrated the origami mechanism of the 2D porphyrinic MOF, whereby the flexible linker acts as a pivoting point. The discovery of the 2D tessellation hidden in the 2D MOF unveils origami mechanics at the molecular level.

Application of The Paris System in neobladder washing cytology: Comparison between the original diagnosis and correlation with histopathology.

BACKGROUND: In urinary diversion after radical cystectomy, the incidence of recurrent urothelial carcinoma (UC) in upper urinary tract or urethra are reported in 2%-17% of the patients. Urine cytology plays a pivotal role in detecting the recurrence of UC. However, cytologic diagnosis in urinary diversion including neobladder is often challenging due to significant degenerative changes and necro-inflammatory background. Since the proposal of The Paris System (TPS) for reporting cytology, the utility of TPS in urinary diversion specimen has not been studied yet. The objective of this study is to evaluate the diagnostic usefulness of TPS compared with the original diagnosis and correlate with the matched histopathological results. METHODS: Urinary diversion cytology specimens with concurrent or subsequent biopsy or resection at EUMC in recent 16 years (from January 2002 to December 2018) are retrospectively reviewed and reclassified according to TPS criteria. The TPS categories and the original diagnoses were compared and correlated with follow-up histology. RESULTS: Concurrent or subsequent biopsy or resection within a 6-month period was available in 45 cases from 28 patients. When applying TPS, the rate of atypical and suspicious categories decreased by 13.4% and 11.1%. Using TPS increased the value of sensitivity, NPV, and accuracy to 93.75%, 93.75%, and 90.91%, respectively. CONCLUSION: Application of TPS reduced the rate of indeterminate diagnoses and moreover, improved the sensitivity and accuracy of urinary diversion cytology. Therefore, we believe that diversion urine cytology diagnosis according to TPS is useful to screen patients for detection of recurrence in routine clinical practice.

A Study of Mycobacterium tuberculosis Detection Using Different Neural Networks in Autopsy Specimens.

Tuberculosis (TB) presents a substantial health risk to autopsy staff, given its three to five times higher incidence of TB compared to clinical staff. This risk is notably accentuated in South Korea, which reported the highest TB incidence rate and the third highest TB mortality rate among OECD member countries in 2020. The standard TB diagnostic method, histopathological examination of sputum or tissue for acid-fast bacilli (AFB) using Ziehl-Neelsen staining, demands microscopic examination of slides at 1000× magnification, which is labor-intensive and time-consuming. This article proposes a computer-aided diagnosis (CAD) system designed to enhance the efficiency of TB diagnosis at magnification less than 1000×. By training nine neural networks with images taken from 30 training slides and 10 evaluation slides at 400× magnification, we evaluated their ability to detect M. tuberculosis. The N model achieved the highest accuracy, with 99.77% per patch and 90% per slide. We discovered that the model could aid pathologists in preliminary TB screening, thereby reducing diagnostic time. We anticipate that this research will contribute to minimizing autopsy staff's infection risk and rapidly determining the cause of death.

Prediction of type 2 diabetes using genome-wide polygenic risk score and metabolic profiles: A machine learning analysis of population-based 10-year prospective cohort study.

BACKGROUND: Previous work on predicting type 2 diabetes by integrating clinical and genetic factors has mostly focused on the Western population. In this study, we use genome-wide polygenic risk score (gPRS) and serum metabolite data for type 2 diabetes risk prediction in the Asian population. METHODS: Data of 1425 participants from the Korean Genome and Epidemiology Study (KoGES) Ansan-Ansung cohort were used in this study. For gPRS analysis, genotypic and clinical information from KoGES health examinee (n = 58,701) and KoGES cardiovascular disease association (n = 8105) sub-cohorts were included. Linkage disequilibrium analysis identified 239,062 genetic variants that were used to determine the gPRS, while the metabolites were selected using the Boruta algorithm. We used bootstrapped cross-validation to evaluate logistic regression and random forest (RF)-based machine learning models. Finally, associations of gPRS and selected metabolites with the values of homeostatic model assessment of beta-cell function (HOMA-B) and insulin resistance (HOMA-IR) were further estimated. FINDINGS: During the follow-up period (8.3 ± 2.8 years), 331 participants (23.2%) were diagnosed with type 2 diabetes. The areas under the curves of the RF-based models were 0.844, 0.876, and 0.883 for the model using only demographic and clinical factors, model including the gPRS, and model with both gPRS and metabolites, respectively. Incorporation of additional parameters in the latter two models improved the classification by 11.7% and 4.2% respectively. While gPRS was significantly associated with HOMA-B value, most metabolites had a significant association with HOMA-IR value. INTERPRETATION: Incorporating both gPRS and metabolite data led to enhanced type 2 diabetes risk prediction by capturing distinct etiologies of type 2 diabetes development. An RF-based model using clinical factors, gPRS, and metabolites predicted type 2 diabetes risk more accurately than the logistic regression-based model. FUNDING: This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korean government (MEST) (No. 2019M3E5D1A02070863 and 2022R1C1C1005458). This work was also supported by the 2020 Research Fund (1.200098.01) of UNIST (Ulsan National Institute of Science & Technology).

Patient-specific molecular response dynamics can predict the possibility of relapse during the second treatment-free remission attempt in chronic myelogenous leukemia.

In chronic myelogenous leukemia (CML), treatment-free remission (TFR) is defined as maintaining a major molecular response (MMR) without a tyrosine kinase inhibitor (TKI), such as imatinib (IM). Several studies have investigated the safety of the first TFR (TFR1) attempt and suggested recommendation guidelines for such an attempt. However, the plausibility and predictive factors for a second TFR (TFR2) have yet to be reported. The present study included 21 patients in chronic myeloid leukemia who participated in twice repeated treatment stop attempts. We develop a mathematical model to analyze and explain the outcomes of TFR2. Our mathematical model framework can explain patient-specific molecular response dynamics. Fitting the model to longitudinal BCR-ABL1 transcripts from the patients generated patient-specific parameters. Binary tree decision analyses of the model parameters suggested a model based predictive binary classification factor that separated patients into low- and high-risk groups of TFR2 attempts with an overall accuracy of 76.2% (sensitivity of 81.1% and specificity of 69.9%). The low-risk group maintained a median TFR2 of 28.2 months, while the high-risk group relapsed at a median time of 3.25 months. Further, our model predicted a patient-specific optimal IM treatment duration before the second IM stop that could achieve the desired TFR2 (e.g., 5 years).

Histologically confirmed distant metastatic urothelial carcinoma from the urinary bladder: a retrospective review of one institution's 20-year experience.

BACKGROUND: Urothelial carcinoma (UC) accounts for roughly 90% of bladder cancer, and has a high propensity for diverse differentiation. Recently, certain histologic variants of UC have been recognized to be associated with unfavorable clinical outcomes. Several UC studies have also suggested that tumor budding is a poor prognostic marker. Distant metastasis of UC after radical cystectomy is not uncommon. However, these metastatic lesions are not routinely confirmed with histology. METHODS: We investigated the histopathologic features of 13 cases of UC with biopsy-proven distant metastases, with a special emphasis on histologic variants and tumor budding. RESULTS: Lymph nodes (6/13, 46%) were the most common metastatic sites, followed by the lung (4/13, 31%), liver (4/13, 31%), and the adrenal gland (2/13, 15%). The histologic variants including squamous (n=1), micropapillary (n=4), and plasmacytoid (n=1) variants in five cases of UC. Most histologic variants (4/5, 80%) of primary UCs appeared in the metastatic lesions. In contrast, high-grade tumor budding was detected in six cases (46%), including one case of non-muscle invasive UC. Our study demonstrates that histologic variants are not uncommonly detected in distant metastatic UCs. Most histologic variants seen in primary UCs persist in the distant metastatic lesions. In addition, high-grade tumor budding, which occurs frequently in primary tumors, may contribute to the development of distant metastasis. CONCLUSIONS: Therefore, assessing the presence or absence of histologic variants and tumor budding in UCs of the urinary bladder, even in non-muscle invasive UCs, may be useful to predict distant metastasis.

Double cocktail immunostains with high molecular weight cytokeratin and GATA-3: useful stain to discriminate in situ involvement of prostatic ducts or acini from stromal invasion by urothelial carcinoma in the prostate.

BACKGROUND: Distinguishing prostatic stromal invasion (PSI) by urothelial carcinoma (UC) from in situ UC involving prostatic ducts or acini with no stromal invasion (in situ involvement) may be challenging on hematoxylin and eosin stained sections. However, the distinction between them is important because cases with PSI show worse prognosis. This study was performed to assess the utility of double cocktail immunostains with high molecular weight cytokeratin (HMWCK) and GATA-3 to discriminate PSI by UC from in situ UC involvement of prostatic ducts or acini in the prostate. METHODS: Among 117 radical cystoprostatectomy specimens for bladder UCs, 25 cases showed secondary involvement of bladder UC in prostatic ducts/acini only or associated stromal invasion and of these 25 cases, seven cases revealed equivocal PSI. In these seven cases with equivocal PSI, HMWCK, and GATA-3 double immunohistochemical stains were performed to identify whether this cocktail stain is useful to identify the stromal invasion. RESULTS: In all cases, basal cells of prostate glands showed strong cytoplasmic staining for HMWCK and UC cells showed strong nuclear staining for GATA-3. In cases with stromal invasion of UC, GATA-3-positive tumor cells in the prostatic stroma without surrounding HMWCK-positive basal cells were highlighted and easily recognized. Among seven equivocal cases, two cases showed PSI and five in situ UC in the prostate. In two cases, the original diagnoses were revised. CONCLUSIONS: Our study suggested that HMWCK and GATA-3 double stains could be utilized as an adjunct method in the distinction between PSI by UC from in situ UC involving prostatic ducts or acini.

Privacy-Preserving Predictive Modeling: Harmonization of Contextual Embeddings From Different Sources.

BACKGROUND: Data sharing has been a big challenge in biomedical informatics because of privacy concerns. Contextual embedding models have demonstrated a very strong representative capability to describe medical concepts (and their context), and they have shown promise as an alternative way to support deep-learning applications without the need to disclose original data. However, contextual embedding models acquired from individual hospitals cannot be directly combined because their embedding spaces are different, and naive pooling renders combined embeddings useless. OBJECTIVE: The aim of this study was to present a novel approach to address these issues and to promote sharing representation without sharing data. Without sacrificing privacy, we also aimed to build a global model from representations learned from local private data and synchronize information from multiple sources. METHODS: We propose a methodology that harmonizes different local contextual embeddings into a global model. We used Word2Vec to generate contextual embeddings from each source and Procrustes to fuse different vector models into one common space by using a list of corresponding pairs as anchor points. We performed prediction analysis with harmonized embeddings. RESULTS: We used sequential medical events extracted from the Medical Information Mart for Intensive Care III database to evaluate the proposed methodology in predicting the next likely diagnosis of a new patient using either structured data or unstructured data. Under different experimental scenarios, we confirmed that the global model built from harmonized local models achieves a more accurate prediction than local models and global models built from naive pooling. CONCLUSIONS: Such aggregation of local models using our unique harmonization can serve as the proxy for a global model, combining information from a wide range of institutions and information sources. It allows information unique to a certain hospital to become available to other sites, increasing the fluidity of information flow in health care.

Privacy-Preserving Patient Similarity Learning in a Federated Environment: Development and Analysis.

BACKGROUND: There is an urgent need for the development of global analytic frameworks that can perform analyses in a privacy-preserving federated environment across multiple institutions without privacy leakage. A few studies on the topic of federated medical analysis have been conducted recently with the focus on several algorithms. However, none of them have solved similar patient matching, which is useful for applications such as cohort construction for cross-institution observational studies, disease surveillance, and clinical trials recruitment. OBJECTIVE: The aim of this study was to present a privacy-preserving platform in a federated setting for patient similarity learning across institutions. Without sharing patient-level information, our model can find similar patients from one hospital to another. METHODS: We proposed a federated patient hashing framework and developed a novel algorithm to learn context-specific hash codes to represent patients across institutions. The similarities between patients can be efficiently computed using the resulting hash codes of corresponding patients. To avoid security attack from reverse engineering on the model, we applied homomorphic encryption to patient similarity search in a federated setting. RESULTS: We used sequential medical events extracted from the Multiparameter Intelligent Monitoring in Intensive Care-III database to evaluate the proposed algorithm in predicting the incidence of five diseases independently. Our algorithm achieved averaged area under the curves of 0.9154 and 0.8012 with balanced and imbalanced data, respectively, in κ-nearest neighbor with κ=3. We also confirmed privacy preservation in similarity search by using homomorphic encryption. CONCLUSIONS: The proposed algorithm can help search similar patients across institutions effectively to support federated data analysis in a privacy-preserving manner.

Pitfalls of Frozen Section Diagnosis for Paraganglioma: A Clinicopathologic Analysis and Review of the Literature.

Few paraganglioma (PG) cases include frozen section diagnoses, and therefore, the accuracy of frozen section diagnosis for PG remains unknown. To better understand the histologic characteristics and pitfalls of frozen section findings for PG, 15 PG cases with frozen section diagnoses were selected from 12 articles through PubMed (1984-2015). In addition, we included 3 cases of PG for which intraoperative consultations were requested during a 5-year period (2012-2016) in 2 hospitals. Seven PGs were from the thyroid; 2 from the pancreas; 4 from the mediastinum, retroperitoneum, or mesentery; 1 from the middle ear; and 4 from the urinary bladder (UB). Out of 18 PGs, correct diagnoses were rendered in only 2 cases, and no thyroid or UB PGs were correctly diagnosed on intraoperative consultation. Thyroid PGs were frequently misdiagnosed as medullary thyroid carcinomas (4/7, 57%) and UB PGs were frequently misdiagnosed as malignancies.

Interleaved incremental association Markov blanket as a potential feature selection method for improving accuracy in near-infrared spectroscopic analysis.

The interleaved Incremental Association Markov Blanket (inter-IAMB) is described herein as a feature selection method for the NIR spectroscopic analysis of several samples (diesel, gasoline, and etchant solutions). Although the Markov blanket (MB) has been proven to be the minimal optimal set of features (variables) that does not change the original target distribution, variables selected by the existing IAMB algorithm could be redundant and/or misleading as the IAMB requires an unnecessarily large amount of learning data to identify the MB. Use of the inter-IAMB interleaving the grow phase with the shrink phase to maintain the size of the MB as small as possible by immediately eliminating invalid candidates could overcome this drawback. In this report, a likelihood-ratio (LR)-based conditional independence test, able to handle spectroscopic data normally comprising a large number of continuous variables in a small number of samples, was uniquely embedded in the inter-IAMB and its utility was evaluated. The variables selected by the inter-IAMB in complexly overlapped and feature-indistinct NIR spectra were used to determine the corresponding sample properties. For comparison, the properties were also determined using the IAMB-selected variables as well as the whole variables. The inter-IAMB was more effective in the selection of variables than the IAMB and thus able to improve the accuracy in the determination of the sample properties, even though a smaller number of variables was used. The proposed LR-embedded inter-IAMB could be a potential feature selection method for vibrational spectroscopic analysis, especially when the obtained spectral features are specificity-deficient and extensively overlapped.

Evaluation of Ki-67 Index in Core Needle Biopsies and Matched Breast Cancer Surgical Specimens.

CONTEXT: - The Ki-67 index is strongly prognostic and is used as a surrogate marker to distinguish luminal A from luminal B breast cancer types. OBJECTIVE: - To investigate differences in Ki-67 index between core needle biopsy samples and matched surgical samples in breast cancer. DESIGN: - We included patients with invasive breast cancer who did not receive neoadjuvant therapy. A total of 89 pairs of core needle biopsies and surgical specimens were collected, and the Ki-67 index was assessed in hot spot areas using an image analyzer. We applied a 14% Ki-67 index to define low versus high groups. RESULTS: - The Ki-67 index was significantly higher in core needle biopsies than in surgical specimens ( P < .001), with a median absolute difference of 3.5%. When we applied 14% as a cutoff, 16 of 89 cases (18%) showed discrepancy. Thirteen cases showed a high Ki-67 index in core needle biopsies but a low Ki-67 index in surgical samples. There were 10 cases (11.2%) that showed discordant luminal A/B types between core needle biopsy and the matched surgical specimen. The reasons for the discordance were poor staining of MIB1 accompanied by fixation issues and intratumoral heterogeneity of the Ki-67 index. CONCLUSIONS: - A significant difference in the Ki-67 index between core biopsy and surgical specimens was observed. Our findings indicate that it may be better to perform the Ki-67 assay on the core needle biopsy and the surgical specimen than on only one sample.

Skin metastases in ovarian clear cell adenocarcinoma: a case report and a review of the literature.

Epithelial ovarian carcinoma is a high mortality neoplasm in gynecologic malignancy. It usually can metastasize to distant organs such as pleura, liver, lung, and lymph nodes. However, the skin metastases are not common and related to very poor prognosis. Here we report a 54-year-old patient with ovarian clear cell carcinoma with skin metastases on the anterior chest at 11 months after initial diagnosis. Although she received palliative chemotherapy, she expired due to disease progression 2 months later after the diagnosis of skin metastases.

Urine cytology findings of primary paraganglioma of the urinary bladder: Case report.

Paraganglioma (PG) of the urinary bladder was detected in a 64-year-old male who was admitted to the hospital with gross hematuria. In voided urine, atypical cells were scattered as nests and single cells on low-power view. On higher-power view, tumor nests were composed of epithelioid cells with fine chromatin and moderate cytoplasm admixed with occasional spindle sustentacular cells. Single cells were discohesive and large with moderate cytoplasm and inconspicuous nucleoli. Subsequent cystoscopy revealed a solid oval mass. Histologically, tumor from the resected bladder showed infiltrating nested tumor cells with abundant cytoplasm. Immunohistochemically, the tumor cells were positive for synaptophysin, chromogranin, and CD56. The patient underwent partial cystectomy and was discharged without complications. Diagn. Cytopathol. 2017;45:350-353. © 2016 Wiley Periodicals, Inc.

Three-dimensional assessment of condylar surface changes and remodeling after orthognathic surgery.

PURPOSE: This study was performed to evaluate condylar surface changes and remodeling after orthognathic surgery using three-dimensional computed tomography (3D CT) imaging, including comparisons between the right and left sides and between the sexes. MATERIALS AND METHODS: Forty patients (20 males and 20 females) who underwent multi-detector CT examinations before and after surgery were selected. Three-dimensional images comprising thousands of points on the condylar surface were obtained before and after surgery. For the quantitative assessment of condylar surface changes, point-to-point (preoperative-to-postoperative) distances were calculated using D processing software. These point-to-point distances were converted to a color map. In order to evaluate the types of condylar remodeling, the condylar head was divided into six areas (anteromedial, anteromiddle, anterolateral, posteromedial, posteromiddle, and posterolateral areas) and each area was classified into three types of condylar remodeling (bone formation, no change, and bone resorption) based on the color map. Additionally, comparative analyses were performed between the right and left sides and according to sex. RESULTS: The mean of the average point-to-point distances on condylar surface was 0.11±0.03 mm. Bone resorption occurred more frequently than other types of condylar remodeling, especially in the lateral areas. However, bone formation in the anteromedial area was particularly prominent. No significant difference was found between the right and left condyles, but condylar surface changes in males were significantly larger than in females. CONCLUSION: This study revealed that condylar remodeling exhibited a tendency towards bone resorption, especially in the lateral areas. Condylar surface changes occurred, but were small.

Bilateral postoperative maxillary cysts after orthognathic surgery: A case report.

Postoperative maxillary cysts are locally aggressive lesions, usually developing as delayed complications many years after radical antral surgery. This report describes a case of bilateral postoperative maxillary cysts following orthognathic surgery performed approximately 21 years previously. The patient complained of stinging pain on her right cheek. Radiographic examination revealed low-attenuation lesions on both maxillary sinuses with discontinuously corticated margins without distinct expansion or bone destruction. The cysts were enucleated with the removal of metal plates and screws for pain relief. Histopathological examination confirmed the diagnosis of postoperative maxillary cysts lined by ciliated, pseudostratified columnar cells. The patient has remained asymptomatic thus far, and there was no evidence of local recurrence at 21 months of postoperative follow-up.

Four human cases of Diphyllobothrium latum infection.

Diphyllobothrium latum infections in 4 young Korean men detected from 2008 to 2012 are presented. Three were diagnosed based on spontaneously discharged strobila of the adult worm in their feces, and 1 case was diagnosed by finding the worm at colonoscopy examination in a local clinic. The morphologic characteristics of the gravid proglottid and eggs were consistent with D. latum. All patients were treated with praziquantel 15 mg/kg, and follow-up stool examinations were done at 2 months after the medication. The main clinical complaints were intermittent gastrointestinal troubles such as indigestion, abdominal distension, and spontaneous discharge of tapeworm's segments in their feces. The most probable source of infection was the flesh of salmon or trout according to a patient's past history. These are the 45th to 48th recorded cases diagnosed by the adult worm in the Republic of Korea since 1971.

Isolation and characterization of a Glutamate decarboxylase (GAD) gene and their differential expression in response to abiotic stresses from Panax ginseng C. A. Meyer.

Glutamate decarboxylase (GAD) catalyzes the conversion of L-glutamate to γ-aminobutyric acid (GABA). A full-length cDNA encoding GAD (designated as PgGAD) was isolated and characterized from the root of Panax ginseng C. A. Meyer. The length cDNA of PgGAD was 1881 bp and contained a 1491 bp open reading frame (ORF) encoding a glutamate decarboxylase protein of 496 amino acids, possessing a Ser-X-X-Lys active site, which belongs to the GAD group. The deduced amino acid sequence of the PgGAD was classified in the plant GAD family and has 76-85% high similarity with other plants as like petunia, Arabidopsis, tomato. Secondary structure of PgGAD was predicted by using SOPMA software program. Southern blot analysis of genomic DNA suggests that, there is more than one copy of the PgGAD gene. The organ specific gene expression pattern also studied in P. ginseng seedlings, in which the stem showed elevated expression than root, leaf, bud and rhizomes. Along with this, we also confirmed the gene expression of PgGAD under various abiotic stresses like temperature stress, osmotic stress, anoxia, oxidative stress, and mechanical damage. Temporal analysis of gene expression except exposure of oxidative stress revealed an enhanced expression after each stresses. The enzyme activity of PgGAD was stimulated to 2-fold under cold stress.

Isolation and characterization of a novel short-chain alcohol dehydrogenase gene from Panax ginseng.

The cDNA of alcohol dehydrogenase (PgADH) was isolated and characterized from the leaf of Panax ginseng. The cDNA had an open reading frame of 801 bp and a deduced amino acid sequence of 266 residues. The calculated molecular mass of the mature protein is approximately 29 kDa with a predicated isoelectric point of 6.84. Homology analysis revealed that the deduced amino acid of PgADH shares a high degree of homology with the short-chain ADH proteins of other plants. Genomic DNA hybridization analysis indicated that PgADH represents a multi-gene family. The expression of PgADH under various environmental stresses was analyzed at different time points using real-time PCR. ABA, SA and especially JA (80-fold) significantly induced PgADH expression within 24 h of treatment. The positive responses of PgADH to abiotic stimuli suggest that ginseng ADH may protect against hormone-related environmental stresses.

Isolation of S-adenosyl-L-methionine synthetase gene from Panax ginseng C.A. meyer and analysis of its response to abiotic stresses.

A cDNA clone containing a S-adenosyl-L-methionine synthetase (SAMS) gene, named as PgSAM, was isolated from a commercial medicinal plant Panax ginseng. PgSAM is predicted to encode a precursor protein of 307 amino acid residues, and its sequence shares high homology with a number of other plant SAMS. PgSAM is expressed at different levels in various organs of ginseng. The expression of PgSAM in adventitious roots and hairy roots of P. ginseng were analyzed using reverse transcriptase (RT)-PCR and real-time PCR under various abiotic stresses. Salt, salicylic acid, abscisic acid and chilling stresses induced PgSAM significantly at different time points within 2-72 h post-treatment. This study revealed that PgSAM may help to protect the plants against various abiotic stresses.