Deep-learning model to improve histological grading and predict upstaging of atypical ductal hyperplasia / ductal carcinoma in situ on breast biopsy.

AIMS: Risk stratification of atypical ductal hyperplasia (ADH) and ductal carcinoma in situ (DCIS), diagnosed using breast biopsy, has great clinical significance. Clinical trials are currently exploring the possibility of active surveillance for low-risk lesions, whereas axillary lymph node staging may be considered during surgical planning for high-risk lesions. We aimed to develop a machine-learning algorithm based on whole-slide images of breast biopsy specimens and clinical information to predict the risk of upstaging to invasive breast cancer after wide excision. METHODS AND RESULTS: Patients diagnosed with ADH/DCIS on breast biopsy were included in this study, comprising 592 (740 slides) and 141 (198 slides) patients in the development and independent testing cohorts, respectively. Histological grading of the lesions was independently evaluated by two pathologists. Clinical information, including biopsy method, lesion size, and Breast Imaging Reporting and Data System (BI-RADS) classification of ultrasound and mammograms, were collected. Deep DCIS consisted of three deep neural networks to evaluate nuclear grade, necrosis, and stromal reactivity. Deep DCIS output comprised five parameters: total patches, lesion extent, Deep Grade, Deep Necrosis, and Deep Stroma. Deep DCIS highly correlated with the pathologists' evaluations of both slide- and patient-level labels. All five parameters of Deep DCIS were significantly associated with upstaging to invasive carcinoma in subsequent wide excisional specimens. Using multivariate logistic regression, Deep DCIS predicted upstaging to invasive carcinoma with an area under the curve (AUC) of 0.81, outperforming pathologists' evaluation (AUC, 0.71 and 0.69). After including clinical and hormone receptor status information, performance further improved (AUC, 0.87). This combined model retained its predictive power in two subgroup analyses: the first subgroup included unequivocal DCIS (excluding cases of ADH and DCIS suspicious for microinvasion) (AUC, 0.83), while the second excluded cases of high-grade DCIS (AUC, 0.81). The model was validated in an independent testing cohort (AUC, 0.81). CONCLUSION: This study demonstrated that deep-learning models can refine histological evaluation of ADH and DCIS on breast biopsies, which may help guide future treatment planning.

Lunasin ameliorates glucose utilization in C2C12 myotubes and metabolites profile in diet-induced obese mice benefiting metabolic disorders.

AIMS: Obesity is the main cause of low-grade inflammation and oxidation, resulting in insulin resistance. This study aimed to investigate the effects of a seed peptide lunasin on glucose utilization in C2C12 myotubes and the metabolite profiles in obese mice. MAIN METHODS: C2C12 myotubes were challenged by palmitic acid (PA) to mimic the obese microenvironment and inflammation, cell vitality, and glucose utilization were determined. C57BL6/j mice were divided into low-fat diet (LF), high-fat diet (HF), and HF with intraperitoneally injected lunasin (HFL) groups. Glucose intolerance and metabolite profiles of the tissues were analyzed. KEY FINDINGS: In vitro, C2C12 myotubes treated with lunasin showed decreased proinflammatory cytokines and increased cell vitality under palmitic acid conditions. Lunasin improved glucose uptake and glucose transporter 4 expression by activating insulin receptor substrate-1 and AKT phosphorylation. Next-generation sequencing revealed that lunasin regulates genes expression by promoting insulin secretion and decreasing oxidative stress. In vivo, HF mice showed increased tricarboxylic acid cycle and uric acid metabolites but decreased bile acids metabolites and specific amino acids. Lunasin intervention improved glucose intolerance and modulated metabolites associated with increased insulin sensitivity and decreased metabolic disorders. SIGNIFICANCE: This study is the first to reveal that lunasin is a promising regulator of anti-inflammation, anti-oxidation, and glucose utilization in myotubes and ameliorating glucose uptake and metabolite profiles in obese mice, contributing to glucose homeostasis and benefiting metabolic disorders.

Necrosis in lymph nodes and their differential diagnoses: application of reticulin staining.

This study aimed to enhance the histopathological diagnosis of necrotic lymph node specimens. A chart review was conducted, revealing that the most common causes of lymph node necrosis were Kikuchi disease (33%), granulomatous inflammation (25%), metastasis (17%), and lymphomas (12%). Histological analysis of necrotic tissue in 333 specimens demonstrated significant differences between the four diseases. The necrotic tissue of Kikuchi disease was amorphous, and hypercellular, and exhibited karyorrhexis and congestion. Granulomatous inflammation presented amorphous necrotic tissue with a nodular-like pattern. Metastasis exhibited heterogeneous morphology that varied between cancer types. Lymphomas displayed extensive necrosis with ghost cells, congestion, and bubbles. Reticulin staining patterns also differed between diseases. Kikuchi disease and lymphomas exhibited preserved reticular fiber networks in the necrotic tissue, resembling the viable tissue. Granulomatous inflammation and metastasis showed disrupted reticular fiber networks in the necrotic tissue. Based on these findings, histological features and reticulin staining patterns can aid in diagnosing Kikuchi disease, granulomatous inflammation, metastasis, and lymphomas in necrotic lymph node specimens.

Pre- and Post-Operative Education and Health-Related Quality of Life for Patients with Hip/Knee Replacement and Hip Fracture.

Arthroplasty for the hip/knee and surgeries for hip fractures are increasing worldwide. The aims of this study were to investigate changes in health-related quality of life (HRQOL) after surgery with an early mobility education program, and to explore their associations with pain and anxiety. Pain intensity and anxiety were assessed with the visual analogue scale (VAS) and Beck Anxiety Inventory (BAI), and HRQOL was assessed with the Short Form-36 (SF-36). The physical component summary (PCS) and mental component summary (MCS) and eight subscales of the SF-36 were calculated. At pre-operation, the patients suffered from moderate pain and mild anxiety, and their HRQOL scores were low (4.9, 7.8, 35.4, and 48.2 for the VAS, BAI, PCS, and MCS, respectively). The pain, anxiety, and HRQOL improved after surgery and had moderate to large effect sizes at 6-month follow-up (Glass's delta = 1.23, 0.88, 0.81, and 0.67 for VAS, BAI, PCS, and MCS, respectively). Pain and anxiety were strongly correlated to HRQOL at each stage, with the maximum correlation (r = -0.34 to -0.93) reached at 6-month follow-up. The surgery effectively improves HRQOL, as the reduced pain and anxiety lead to better physical and mental HRQOL.

Discoloration Improvement by Mechanically-Milled Binary Oxides as Radiopacifier for Mineral Trioxide Aggregates.

Mineral trioxide aggregates (MTA) have been widely used in endodontic treatments, but after some time, patients suffer tooth discoloration due to the use of bismuth oxide (Bi2O3) as a radiopacifier. Replacement of Bi2O3 with high energy ball-milled single (zirconia ZrO2; hafnia, HfO2; or tantalum pentoxide, Ta2O5) or binary oxide powder was attempted, and corresponding discoloration improvement was investigated in the present study. Bi2O3-free MTA is expected to exhibit superior discoloration. The radiopacity, diametral tensile strength, and discoloration of MTA-like cements prepared from the as-milled powder were investigated. Experimental results showed that MTA-like cements prepared using Ta2O5 exhibited a slightly higher radiopacity than that of HfO2 but had a much higher radiopacity than ZrO2. Milling treatment (30 min to 3 h) did not affect the radiopacities significantly. These MTA-like cements exhibited superior color stability (all measured ΔE00 < 1.0) without any perceptible differences after UV irradiation. MTA-like cements prepared using ZrO2 exhibited the best color stability but the lowest radiopacity, which can be improved by introducing binary oxide. Among the investigated samples, MTA-like cement using (ZrO2)50(Ta2O5)50 exhibited excellent color stability and the best overall performance with a radiopacity of 3.25 mmAl and a diametral tensile strength of 4.39 MPa.

Seed peptide lunasin ameliorates obesity-induced inflammation and regulates immune responses in C57BL/6J mice fed high-fat diet.

Obesity causes immune cells to infiltrate into adipose tissues and secrete proinflammatory mediators, promoting the development of chronic diseases. The seed peptide lunasin has been reported to have several bioactivities. We aimed to investigate the immunomodulatory properties of lunasin in obese models. Female and male C57BL/6J mice were divided into three groups: low-fat diet (LF), high-fat diet (HF), and HF with an intraperitoneal injection of lunasin (HFL). In females, lunasin decreased the levels of monocyte chemoattractant protein-1 (MCP-1), interleukin (IL)-1ß, and tumor necrosis factor (TNF-α) produced in peritoneal macrophages, indicating a decrease in F4/80+ macrophage infiltration, especially the CD11c + M1 phenotype. Serum leptin and tissue-oxidized lipid malondialdehyde levels were decreased in the HFL group. In males, lunasin normalized the obesity-induced increase in spleen size and splenocyte numbers. Moreover, lunasin inhibited IL-6 secretion while promoting interferon gamma (IFN-γ) and IL-2 production in the splenocytes. In vitro, lunasin increased EL-4 T-cell proliferation and IL-2 production in activated T cells under obese conditions. Thus, lunasin is a potential natural compound that promotes immunomodulation in both female and male obese mice in a sex-dependent manner. Furthermore, lunasin mediates the anti-inflammatory response and enhances the T helper type 1 cell response to obesity-related immune disorders.

Estimation of students' exposure to metal concentrations from river-dust episodes during 1994-2012.

Two elementary schools (Shiuguang and Fongrong) from Yulin County in Taiwan, near a main area of potential exposure to Aeolian river-dust, were selected to collect outdoor and indoor PM10 aerosols and to measure five metals in PM10 (As, Ni, Cr, Cd, and Mn). Significant relationships (p < 0.01) were found between outdoor PM10 concentrations at Lunbei's air quality monitoring station and the two elementary schools. The outdoor PM10 concentrations at the monitoring station and the schools' indoor PM10 concentrations also showed significant correlations. This study also established a relationship between the outdoor and indoor concentrations of PM10 and metals in the schools. Estimations were made regarding students' 8 h of exposure to metal concentrations from river-dust episodes during 1994-2012, based on correlation equations that were shown to be statistically significant.

Evaluation of the vehicle contributions of metals to indoor environments.

A large number of diesel vehicles carrying gravel and sand shuttle back and forth every day on the major thoroughfares (Tai-16 and Tai-21) from Shinyi to Jiji in Nantou, Taiwan. A total of 10 stations along the major thoroughfares were selected as the exposure sites, whereas a small village located ∼9 km from a main traffic route was selected as the control site. Outdoor and indoor aerosol samples were collected using high-volume samplers and Harvard samplers, respectively. The metal concentrations of outdoor and indoor PM(10) at the exposure sites were, respectively, higher than those at the control site. The plots between metal contents in the aerosols and road dust showed that diesel vehicles contributed significant amounts of metals to the outdoor and indoor aerosols at the exposure sites. Household dust samples along the roadside within 30 m of the main road in the small towns were collected using the wipe method. Based on the results of principal component analysis (PCA), three major components for household dust were identified: resuspended from road dust, brake wear and diesel emissions. Enrichment factors were applied to assess the contribution of pollution sources to household dust. These factors were calculated with respect to unpolluted river dust samples (EF(river)) and road dust (EF(road)). The differences between EF(river) and EF(road) could be mainly attributed to the effects of resuspension by passing vehicles. Approximately 72%, 68%, 68%, 73% and 86% of the vehicle-related metals Pb, Zn, Cu, Ni and Mo content, respectively, in household dust were the result of the resuspension of road dust by passing vehicles. The data of daily intakes of five metals (i.e., Fe, Pb, Cu, Ni and Mo) from inhalation and ingestion pathways showed that the doses from the ingestion pathway were much higher than those from the inhalation pathway.