A reliable diabetic retinopathy grading via transfer learning and ensemble learning with quadratic weighted kappa metric.

The most common eye infection in people with diabetes is diabetic retinopathy (DR). It might cause blurred vision or even total blindness. Therefore, it is essential to promote early detection to prevent or alleviate the impact of DR. However, due to the possibility that symptoms may not be noticeable in the early stages of DR, it is difficult for doctors to identify them. Therefore, numerous predictive models based on machine learning (ML) and deep learning (DL) have been developed to determine all stages of DR. However, existing DR classification models cannot classify every DR stage or use a computationally heavy approach. Common metrics such as accuracy, F1 score, precision, recall, and AUC-ROC score are not reliable for assessing DR grading. This is because they do not account for two key factors: the severity of the discrepancy between the assigned and predicted grades and the ordered nature of the DR grading scale. This research proposes computationally efficient ensemble methods for the classification of DR. These methods leverage pre-trained model weights, reducing training time and resource requirements. In addition, data augmentation techniques are used to address data limitations, improve features, and improve generalization. This combination offers a promising approach for accurate and robust DR grading. In particular, we take advantage of transfer learning using models trained on DR data and employ CLAHE for image enhancement and Gaussian blur for noise reduction. We propose a three-layer classifier that incorporates dropout and ReLU activation. This design aims to minimize overfitting while effectively extracting features and assigning DR grades. We prioritize the Quadratic Weighted Kappa (QWK) metric due to its sensitivity to label discrepancies, which is crucial for an accurate diagnosis of DR. This combined approach achieves state-of-the-art QWK scores (0.901, 0.967 and 0.944) in the Eyepacs, Aptos, and Messidor datasets.

Novel Combined Preparation and Investigation of Bergenin-Loaded Albumin Nanoparticles for the Treatment of Acute Lung Injury: In Vitro and In Vivo Evaluations.

A new method for targeting lung infections is of great interest using biodegradable nanoparticles. In this study, bergenin-loaded BSA NPs were developed against lung injury. Briefly, bergenin-loaded bovine serum albumin nanoparticles (BG@BSA NPs) were synthesized and characterized. HPLC recorded the major peak of bergenin. UV-Vis spectra had an absorbance at 376 nm. XRD revealed the presence of crystalline particles. FTIR confirmed the occurrence of functionalized molecules in the synthesized NPs. The particles were highly stable with a net negative charge of - 24.2. The morphology of NPs was determined by SEM and TEM. The mean particle size was 124.26 nm. The production of NO by NR8383 cells was decreased by BG@BSA NPs. Also, in mice, lipopolysaccharide-mediated acute lung inflammation was induced. BG@BSA NPs reduced macrophages and neutrophils in BALF and remarkably enhanced wet weight-to-dry weight (W/D) ratios and myeloperoxidase (MPO) activity. Further, BG@BSA NPs inhibited the production of inflammatory cells as well as tumor necrosis factor. The histopathological studies revealed that the damage and neutrophil infiltration were greatly inhibited by BG@BSA NPs. This indicates that BG@BSA NPs may be used to treat lung infections. Therefore, this study has given new insight into producing an active drug for the treatment of lung-associated diseases in the future.

SLC34A2 Up-regulation And SLC4A4 Down-regulation Correlates With Invasion, Metastasis, And The MAPK Signaling Pathway In Papillary Thyroid Carcinomas.

Papillary thyroid carcinoma (PTC) is one of the fastest growing endocrine system malignant carcinomas detected over the past decade. Unfortunately, more than 25% of PTC patients are characterized by their aggressiveness and subsequent metastasis; these characteristics usually indicate poor prognosis. Recently, increasing evidence has suggested that solute carrier (SLC) transporters may play a pivotal role in the initiation, invasion and metastasis of human carcinoma. However, the expression and clinicopathological significance of SLC transporters in patients with PTC remains undetermined. In this study, we aimed to elucidate how the differential expression of SLC transporters affects clinicopathological features, as well as determine the possible regulatory signaling pathways involved. Three differentially expressed SLC transporters were screened from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) database using a bioinformatics approach. The results indicated that high SLC34A2 and low SLC4A4 protein expression exhibited a higher percentage of capsular invasion and extra-thyroid metastasis in patients. Logistic regression analysis showed that high SLC34A2 expression in tumors was identified as an independent risk factor for capsular invasion [odds ratio (OR)=11.400, 95% confidence interval (CI)=1.733-74.995, P=0.011] and extra-thyroid metastasis (OR=4.920, 95%CI=1.234-19.623, P=0.024), while low SLC4A4 expression in tumors was only identified as independent risk factors for extra-thyroid metastasis (OR=8.568, 95%CI =1.186-61.906, P=0.033). Specifically, for tumors with capsular invasion and extra-thyroid metastasis, the protein expression staining of SLC34A2 was markedly enhanced in the cytoplasm of follicular epithelial cells, contrastingly, SLC4A4 expression was notably weakened in the cytomembrane and nucleus. Intriguingly, both high SLC34A2 and low SLC4A4 protein expression were significantly linked to a high urinary iodine concentration in patients with PTC. Mechanistically, compared with adjacent normal thyroids, p-ERK was significantly up-regulated by 17.8% in the invading tumor; p-ERK, p-JNK, and p-P38 were markedly up-regulated by 29.2%, 67.1%, and 38.9% for metastatic tumors, respectively. Importantly, SLC4A4 negatively correlated with p-JNK (r=-0.696, P= 0.004) and p-P38 (r=-0.534, P=0.049). In conclusion, we suggest that up-regulated SLC34A2 (mainly in the cytoplasm) and down-regulated SLC4A4 (mainly in the cytomembrane and nucleus), which might be attributed to excess iodine intake, were closely linked to extra-thyroid metastasis in PTCs. Furthermore, this effect of SLC4A4 may be through the activation of JNK/P38 MAPK signaling pathway. Future in vivo and in vitro gain- or loss-of-function experiments are needed to verify these findings and further elucidate the deeper molecular mechanisms.

Association between excessive chronic iodine exposure and the occurrence of papillary thyroid carcinoma.

The aim of the present study was to elucidate the association between excessive chronic iodine exposure and the risk of developing papillary thyroid carcinoma (PTC). The demographic information and pathological characteristics of patients with thyroid nodules were retrieved from medical records at The Second Hospital of Shandong University. A fasting urine specimen was collected, and creatinine and urinary iodine concentration (UIC) were determined. The water iodine data from the domicile districts of these patients were collated from published reports. The results revealed that almost half of the patients with PTC (44.3%) also exhibited a high UIC (≥300 µg/l). Multivariate analysis revealed that the adjusted odds ratio for high UIC was 3.987 (95% CI: 1.355-11.736) and the adjusted area under the receiver operating characteristic curve was 0.776 (95% CI: 0.687-0.864), which was associated with PTC risk in patients with thyroid nodules. Integrated ecological assessment of chronic iodine exposures demonstrated that >80% (81.4%) of the patients with PTC who also exhibited a high UIC were from historically non-iodine-deficient regions, and 66.7% of patients with PTC who resided in historically iodine-excessive regions were characterized by high UICs. Importantly, a high UIC was significantly associated with capsular invasion and extrathyroid metastasis (P<0.05). Moreover, self-matching results indicated that, in patients with PTC, there were no significant differences in UIC grading between the pre- and postoperative specimens. In conclusion, excessive chronic iodine exposure is significantly associated with the risk of PTC, which contributes to increased capsular invasion and extrathyroid metastases. However, further research is required to validate these findings and to elucidate the potential molecular mechanisms involved.

Downregulation of Calbindin 1 by miR-454-3p Suppresses Cell Proliferation in Nonsmall Cell Lung Cancer In Vitro.

BACKGROUND: Calbindin 1 (CALB1), a constituent Ca2+-binding protein, has been reported to prevent apoptotic death in tumor cells. However, the microRNA-mediated regulatory mechanism of CALB1 expression in nonsmall cell lung cancer (NSCLC) has not been reported so far. METHODS AND RESULTS: In this study, CALB1 was found to be overexpressed in NSCLC tissues through the immunohistochemistry assay. Higher CALB1 expression levels were significantly associated with the tumor-node-metastasis (TNM) stage. Moreover, higher expression of CALB1 predicts poor survival in NSCLC patients using the Kaplan-Meier plotter online analysis. In addition, miR-454-3p was predicted to target CALB1 using a software algorithm, validated by the luciferase assay, and analyzed by quantitative polymerase chain reaction and Western blot. The authors further found that miR-454-3p was downregulated in NSCLC tissues and cell lines. Downregulation of CALB1 or upregulation of miR-454-3p significantly suppressed NSCLC cell proliferation and induced cell apoptosis as shown by CCK-8 and flow cytometry analysis, respectively. CONCLUSIONS: Our results suggest that CALB1 is a direct target of miR-454-3p and downregulation of CALB1 by miR-454-3p suppressed NSCLC cell functions, which may shed light on its potential application in NSCLC therapy.

Meta-analysis Comparison of Bilateral Axillo-Breast Approach Robotic Thyroidectomy and Conventional Thyroidectomy.

OBJECTIVE: Despite gaining popularity, bilateral axillo-breast approach robotic thyroidectomy (BABA RT) remains controversial. We performed a meta-analysis to evaluate the safety and effectiveness of BABA RT compared with open thyroidectomy (OT) in thyroid disease. METHODS: A literature search was conducted using various databases, including PubMed, Web of Science, and Cochrane Library, up to February 2018. Outcomes of interest included patient characteristics, surgical outcomes, adverse events, complications, and surgical completeness. RESULTS: A total of 11 publications including 2733 patients (1070 in the BABA RT and 1663 in the open group) were finally selected for the meta-analysis. BABA RT was associated with an equivalent complication rate, including transient and permanent hypocalcemia, transient and permanent recurrent laryngeal nerve palsy, bleeding, chyle leakage, and seroma, as well as surgical outcomes including tumor size, length of hospital stay, total drain amount, and pain score. BABA RT was also associated with an equivalent surgical completeness, including total dose of radioactive iodine, proportion of stimulated thyroglobulin (sTg) <1.0 ng/mL, and level of sTg. Moreover, BABA RT involved longer operative times (weighted mean difference [WMD] = 110.13; P < .00001), smaller number of retrieved lymph nodes(WMD = -1.26, P = .003), and more cost (WMD = 5811.18; P < .00001) compared with OT. CONCLUSIONS: BABA RT is safe and feasible and provides similar perioperative outcomes and complications when compared with OT. However, BABA RT was associated with longer operating time, fewer retrieved lymph nodes, and more cost. Randomized clinical trials with large samples and longer follow-up data are needed to more rigorously examine this effect.

A Systemic Review of Transoral Thyroidectomy.

BACKGROUND: Transoral thyroidectomy is a kind of "natural orifice transluminal endoscopic surgery (NOTES)" which is now being performed in increasing frequency. However, the safety and feasibility have not been concluded yet. MATERIALS AND METHODS: A systemic literature search was performed in Pubmed, Cochrane, and Embase databases to identify all studies written in English and published up to April 2017. The keywords used were "transoral endoscopic," "transoral robotic," "oral vestibular endoscopic," and "oral vestibular robotic" combined with "thyroidectomy" or "thyroid surgery." RESULTS: Ten articles containing 211 cases matched the review criteria. The weighted average operative time was 119.9 minutes with an average intraoperative blood loss of 35.5 mL while the weighted average length of hospital stay was 4.0 days. The overall conversion rate to open surgery was 1.9%. An overall incidence rate of temporary hypoparathyroidism was 7.1%, temporary recurrent laryngeal nerve injury was 4.3%, whereas of mental nerve palsy was 4.3%. CONCLUSIONS: According to those reviewed literatures, we can conclude that transoral thyroidectomy is safe and feasible in well-selected patients and offers good perioperative and postoperative outcomes.

Integrin ß6 serves as an immunohistochemical marker for lymph node metastasis and promotes cell invasiveness in cholangiocarcinoma.

Cholangiocarcinoma is a devastating malignancy that is notoriously difficult to diagnose and is associated with a high mortality. Despite extensive efforts to improve the diagnosis and treatment of this neoplasm, limited progress has been made. Integrin ß6 is a subtype of integrin that is expressed exclusively on the surfaces of epithelial cells and is associated with a variety of tumors. In the present study, we investigated the expression and roles of integrin ß6 in cholangiocarcinoma. ß6 upregulation in cholangiocarcinoma was correlated with lymph node metastasis and distant metastasis. Moreover, integrin ß6 was identified as a biomarker for the diagnosis of cholangiocarcinoma and an indicator of lymph node metastasis. Integrin ß6 significantly promoted the proliferation, migration and invasion of cholangiocarcinoma cells. Furthermore, integrin ß6 increased Rac1-GTPase, resulting in the upregulation of metalloproteinase-9 (MMP9) and F-actin polymerization. Taken together, our results indicate that integrin ß6 promotes tumor invasiveness in a Rac1-dependent manner and is a potential biomarker for tumor metastasis. Integrin ß6 may help to improve the diagnostic accuracy, and targeting ß6 may be a novel strategy for the treatment of cholangiocarcinoma.

[Applications of video-assisted thoracic surgery for the diagnosis and treatment of patients with small pulmonary nodules].

BACKGROUND AND OBJECTIVE: Chest computed tomography (CT), particularly thin-slice high resolution CT, has low sensitivity and specificity for detecting pulmonary nodules <10 mm in size. This limitation leads to challenges in clinical diagnosis and treatment of small pulmonary nodules. This study introduces the use of video-assisted thoracoscopic surgery (VATS) for the diagnosis and treatment of small pulmonary nodules. METHODS: From November 2009 to May 2012, 64 patients with small pulmonary nodules without prior preoperative pathologic diagnosis were treated by pulmonary wedge resection through VATS. The diagnosis of small pulmonary nodules was established from rapid frozen section. The type of operation depends on the pathology and the condition of the patients. Twenty patients with primary lung cancer were subjected to lobectomy and radical resection of the lymph nodes by complete thoracospic lobectomy or video-assisted thoracoscopic invasive lobectomy. Pulmonary wedge resection was performed in 44 patients, among whom 21 have benign nodule, 18 have precancerous lesion, 3 have metastatic nodule, and 2 have primary lung cancer for which lobectomy was not fit. RESULTS: Confirmative diagnosis is difficult to obtain among patients with small pulmonary nodules. VATS is effective in the diagnosis and treatment of small pulmonary nodules. With VATS, patients with benign small pulmonary nodules can be cured, and patients with primary lung cancer can receive definite diagnosis and effective treatment in time. CONCLUSIONS: CT-guided hook-wire fixation is useful in precise lesion localization for surgical resection.