Impact of polygenic risk score for triglyceride trajectory and diabetic complications in subjects with type 2 diabetes based on large electronic medical record data from Taiwan: a case control study.

BACKGROUND: The prevalence of diabetic dyslipidemia has gradually increased worldwide and individuals with hypertriglyceridemia often have a high polygenic burden of triglyceride (TG)-increasing variants. However, the contribution of genetic variants to dyslipidemia in patients with type 2 diabetes (T2D) remains limited. Therefore, in this study, we aimed to investigate the genetic characteristics of longitudinal changes in TG levels among patients with T2D and summarize the genetic effects of polygenic risk score (PRS) on TG trajectory and risk of diabetic complications. METHODS: We conducted a case-control study. A total of 11,312 patients with T2D with longitudinal TG and genetic data were identified from a large hospital database in Taiwan. We then performed a genome-wide association study and calculated the relative PRS. RESULTS: In total, 21 single-nucleotide polymorphisms (SNPs) related to TG trajectory were identified and yielded an area under the receiver operating characteristic curve (ROC) of 0.712 for high TG trajectory risk among Taiwanese patients with T2D. A cumulative genetic effect was observed for high TG trajectory, even when considering the adherence of a lipid-lowering agent in stratified analysis. An increased PRS increases high TG trajectory risk in a logistic regression model (odds ratio = 1.55; 95% confidence interval [CI] = 1.31-1.83 in the validation cohort). The TG-specific PRS was associated with the risk of diabetic microvascular complications, including diabetic retinopathy and nephropathy (with hazard ratios of 1.11 [95% CI = 1.01-1.21, P = 0.027] and 1.05 [95% CI = 1.01-1.1, P = 0.018], respectively). CONCLUSIONS: This study may contribute to the identification of patients with T2D who are at risk of abnormal TG levels and diabetic microvascular complications using polygenic information.

[Preliminary study on the role and mechanism of IL-6 receptor antagonists in improving post-infarction ventricular arrhythmia].

Objective: To investigate the effect of tocilizumab (TCZ) on ventricular arrhythmias (VAs) after myocardial infarction (MI) in Sprague-Dawley rats and explore its potential mechanism. Methods: The random number table method was used to divide 32 adult male Sprague-Dawley rats into 4 groups: Sham group, TCZ group, MI group and MI+TCZ group, with 8 rats in each group. The MI model was established by ligation of the left anterior descending branch of the coronary artery in the MI and MI+TCZ groups, and only sutured without ligation in the Sham and TCZ groups. TCZ was injected into the left superior cervical ganglion (SCG) of rats in the TCZ and MI+TCZ groups after successful modeling or sham operation, and the same amount of normal saline was injected in the Sham and MI groups. 24 h after successful modeling, ECG of rats in each group was recorded, heart rate variability (HRV, including low frequency power (LF), high frequency power (HF), LF/HF ratio), QT interval, QTc interval were calculated, and left ventricular effective refractory period (ERP) and VA inducibility were measured. Myocardial infarct size and tissue changes were observed with triphenyl tetrazolium chloride staining and HE staining. Real-time PCR analysis was used to detect the messager RNA (mRNA) expression of interleukin-6 (IL-6) and signal transducer and activator of transcription (STAT) 3 in SCG and potassium voltage-gated channel subfamily D member 2 (Kcnd2) in myocardial infarction periphery. The expression of c-fos in SCG was detected by immunofluorescence staining. Results: Compared with Sham group and MI+TCZ group, rats in MI group had higher LF and LF/HF ratio, longer QT interval and QTc interval, more VAs induced, lower HF and shorter ERP (P all<0.05). Triphenyl tetrazolium chloride staining and HE staining showed that rats in the Sham and TCZ groups had normal myocardial tissue structure, those in the MI group had severe myocardial injury, and those in the MI+TCZ group had less myocardial injury than those in the MI group. Real-ime PCR analysis showed that compared with Sham group and MI+TCZ group, mRNA expression levels of IL-6 and STAT3 in SCG of rats in MI group were higher, and mRNA expression level of myocardial Kcnd2 was lower (P all<0.05). Immunofluorescence staining showed that the content of c-fos in SCG of rats in MI group was higher than that of Sham group and MI+TCZ group (P all<0.05). Conclusions: TCZ may reduce neural activity of the SCG after MI by inhibiting the IL-6/STAT3 signaling pathway, thereby alleviating myocardial injury and inhibiting VAs.

Artificial intelligence for ocular oncology.

PURPOSE OF REVIEW: The aim of this article is to provide an update on the latest applications of deep learning (DL) and classical machine learning (ML) techniques to the detection and prognostication of intraocular and ocular surface malignancies. RECENT FINDINGS: Most recent studies focused on using DL and classical ML techniques for prognostication purposes in patients with uveal melanoma (UM). SUMMARY: DL has emerged as the leading ML technique for prognostication in ocular oncological conditions, particularly in UM. However, the application of DL may be limited by the relatively rarity of these conditions.

Incidence and familial clustering of infantile haemangiomas: a multicentre study.

BACKGROUND: The exact incidence of infantile haemangiomas (IH) in the Chinese population is still unknown. A positive family history of IH was considered as a risk factor for the development of IH. OBJECTIVES: This study aims to investigate the incidence of IH in the Chinese population and the mechanism of family history increases the risk for IH development. METHODS: A total of 2489 women and their newborns were enrolled in the prospective study. All newborns were followed up for 12 months to determine whether they developed IH. In addition, 213 IH probands and their 174 siblings were enrolled in the study. The incidence of IH in siblings of the IH probands was investigated. Information regarding risk factors for IH and demographic data were collected on all children. RESULTS: Of the 2572 newborns, 58 IH were identified in 56 (2.2%) newborns. The majority of IH were located on the trunk (46.6%). Siblings of the IH probands were at increased risk for the development of IH (P = 0.024, relative risk 2.451), and the occurrence of prenatal risk factors for IH(P = 0.003) compared with the general population. CONCLUSIONS: Our study showed that the incidence of IH is 2.2% in the Chinese population. Siblings of the individuals with IH were at increased risk for the development of IH may be related to the family clustering of prenatal risk factors for IH. Further exploration of the mechanisms and common features of these prenatal risk factors may help to disclose the origin and pathogenesis of IH.

[The role of preventive pancreatic duct stent placement in preventing acute pancreatitis after endoscopic retrograde cholangiopancreatography].

The aim of this study was to investigate the preventive effect of pancreatic duct stent on acute pancreatitis after endoscopic retrograde cholangiopancreatography. A retrospective analysis of the case data of patients who first underwent endoscopic retrograde cholangiopancreatography for choledocholithiasis in the Beijing Friendship Hospital from January 2015 to December 2019 for 5 years. According to whether the pancreatic duct stent was indwelled during the operation, they were divided into pancreatic duct stent group (147 cases) and non-indwelling pancreatic duct stent group (192 cases). The incidence of acute pancreatitis after endoscopic retrograde cholangiopancreatography was compared between the two groups according to COTTON criteria. Independent sample t test, Pearson Chi-square test (χ2) and Fisher's exact test were used to compare groups' differences. There were 2 cases of acute pancreatitis in the pancreatic duct stent group, all of which improved after 48 hours. There were 22 cases of acute pancreatitis in the non-indwelling pancreatic duct stent group, of which 20 cases improved within 48 hours, and the other 2 cases had severe pancreatitis, which improved and discharged after 30 days of treatment. There was significant difference in the incidence of acute pancreatitis between the pancreatic duct stenting group (1.4%) and the group without placement of pancreatic duct stents (11.5%) (χ²=12.905,P<0.001). In conclusion, Pancreatic duct stent may be an effective method to prevent PEP.

[Efficacy and safety of neoadjuvant toripalimab combined with nimotuzumab and chemotherapy in patients with unresectable stage â £ squamous cell carcinoma of penis].

Objective: To compare the efficacy and safety of neoadjuvant chemotherapy alone or combined with toripalimab and nimotuzumab in patients with unresectable locally advanced or metastatic squamous cell carcinoma of penis. Methods: A total of 33 patients with unresectable squamous cell carcinoma of penis undergoing neoadjuvant chemotherapy alone or combined with toripalimab and nimotuzumab at Sun Yat-sen University Cancer Center from May 2015 to June 2021 were enrolled retrospectively. All the patients were male, with a median age (M(IQR))of 49.0 (13.5) years (range: 30 to 70 years). According to the therapy protocols, patients were divided into the chemotherapy group (16 cases) and the triple combination group (17 cases). Log-rank test was used to compare the progression-free survival and overall survival. χ2 test or Fisher exact method was used to compare the objective response rate, pathological down-stage rate and adverse events between these two groups. Results: The follow-up time was 28.1(19.2) months (range: 1.5 to 33.4 months). Patients of triple combination group were observed significantly longer progression-free survival (30.0 months vs. 8.2 months, χ²=3.998, P=0.046) than those of chemotherapy group. The median overall survival of the triple combination group and chemotherapy group were not reached and 15.2 months (χ²=3.298, P=0.069), respectively. Although there was no significant difference in the subsequent surgical resection rate between these two groups (12/17 vs.11/16, P=1), the objective response rate and the pathological complete response rate in triple combination group were significantly higher than in chemotherapy group (13/17 vs. 6/16, χ²=5.125, P=0.024; 6/7 vs. 0, P=0.001). The main common grade 1 to 2 adverse events in the triple combination group were alopecia (16 cases), anemia (15 cases), and nausea (14 cases). The main common grade 1 to 2 adverse events in the chemotherapy group were anemia (14 cases), alopecia (12 cases), decreased appetite (12 cases), and nausea (11 cases). The incidence of adverse events ≥grade 3 was similar in the triple combination group and chemotherapy group (8/17 vs. 6/16, χ²=0.308, P=0.579). There was no grade 3 adverse event in both groups. Conclusion: Compared with traditional chemotherapy alone, chemotherapy combined with toripalimab and nimotuzumab provides longer progression-free survival and similar toxicity for unresectable stage Ⅳ squamous cell carcinoma of penis.

Healing of sub-critical femoral osteotomies in mice is unaffected by tacrolimus and deletion of recombination activating gene 1.

Clinical management of delayed healing or non-union of long bone fractures and segmental defects poses a substantial orthopaedic challenge. There are suggestions in the literature that bone healing may be enhanced by inhibiting the activities of T and B lymphocytes, but this remains controversial. To examine this matter in more detail, sub-critical-sized segmental defects were created in the femora of mice and it was assessed whether there might be a benefit from the administration of a Food and Drug Administration (FDA)-approved drug that blocks T cell activation (tacrolimus). Defects were stabilised using an internal plate. In certain groups of animals, 1 mg/kg or 10 mg/kg tacrolimus was delivered locally to the defect site for 3 or 7 d using an implanted osmotic pump with a silicon catheter directing drug delivery into the defect area. Healing was monitored by weekly X-ray and assessed at 12 weeks by mechanical testing, µCT and histology. Radiographic and histological evaluations revealed that 100 % of defects healed well regardless of tacrolimus dosage or duration. A comparison of healed C57BL/6 and Rag1-/- femora by µCT and ex vivo torsion testing showed no differences within mouse strains in terms of bone volume, tissue volume, bone volume/tissue volume ratio, shear modulus, torsional rigidity or torsional stiffness. These data failed to support an important role for tacrolimus in modulating the natural healing of segmental defects under those experimental conditions.

The Impact of COVID-19 on Diabetic Retinopathy Monitoring and Treatment.

PURPOSE OF REVIEW: Diabetic retinopathy (DR) is one of the leading causes of vision loss worldwide. Although screening and early treatment guidelines for DR have significantly reduced the disease burden, restrictions related to the COVID-19 pandemic have changed real-world practice patterns in the management of DR. This review summarizes evolving guidelines and outcomes of the treatment of DR in the setting of the pandemic. RECENT FINDINGS: Intravitreal injections for DR have decreased significantly globally during the pandemic, ranging from approximately 30 to nearly 100% reduction, compared to corresponding timepoints in 2019. Most studies on functional outcomes show a decrease in visual acuity on delayed follow-up. Changing practice patterns in the management of DR has led to fewer intravitreal injections and overall reduction in visual acuity on follow-up. As COVID variants emerge, it will be necessary to continue evaluating practice guidelines.

The Role of Ultra-Widefield Fundus Imaging and Fluorescein Angiography in Diagnosis and Treatment of Diabetic Retinopathy.

PURPOSE OF REVIEW: Early detection and treatment are important for preventing vision loss from diabetic retinopathy. Historically, the gold standard for grading diabetic retinopathy has been based on 7-field 30-degree color fundus photographs that capture roughly the central third of the retina. Our aim was to review recent literature on the role of ultra-widefield (allowing capture of up to 82% of the retina in one frame) fundus imaging in screening, prognostication, and treatment of diabetic retinopathy. RECENT FINDINGS: Ultra-widefield fundus imaging can capture peripheral retinal lesions outside the traditional 7-field photographs that may correlate with increased risk of diabetic retinopathy progression. The speed and ability to image through undilated pupils make ultra-widefield imaging attractive for tele-ophthalmology screening. Ultra-widefield fluorescein angiography may help guide targeted laser treatment in eyes with proliferative diabetic retinopathy. Ultra-widefield imaging has potential to help shape new diabetic retinopathy screening, staging, and treatment protocols.

Choriocapillaris flow loss in center-involving retinitis pigmentosa: a quantitative optical coherence tomography angiography study using a novel classification system.

PURPOSE: Choriocapillaris insufficiency may play a role in centripetal retinitis pigmentosa (RP) progression involving the fovea. However, the relationship between choriocapillaris integrity and foveal damage in RP is unclear. We examined the relationship between choriocapillaris flow and the presence of foveal photoreceptor involvement in RP. METHODS: We categorized the severity of central involvement in RP by the occurrence of foveal ellipsoid zone (EZ) disruption: present (severe RP) or absent (mild RP). Using optical coherence tomography angiography (OCTA, AngioVue, Optovue) in cases and unaffected age-matched controls, we compared vessel density (VD) between the groups using the generalized linear mixed model, controlling for age, gender, and scan quality. RESULTS: Fifty-seven eyes (20 severe RP, 18 mild RP, and 19 controls) were included. Foveal and parafoveal mean outer retinal thickness (µm) were lower in severe RP (fovea: 101.3 ± 14.5; parafovea: 68.4 ± 11.7) than controls (fovea: 161.2 ± 8.9; parafovea: 142.1 ± 11.8; p ≤ 0.001) and mild RP (fovea: 162.0 ± 14.7; parafovea: 116.8 ± 29.4; p ≤ 0.0001). Foveal choriocapillaris VD (%) was lower in severe RP (56.7 ± 6.8) than controls (69.9 ± 4.6; p = 0.008) and mild RP (65.3 ± 5.3; p = 0.01). The parafoveal choriocapillaris VD was lower in severe RP than controls (64.4 ± 5.9 vs. 68.3 ± 4.1; p = 0.04) but no different than in mild RP (p = 0.4). CONCLUSION: Choriocapillaris flow loss was associated with fovea-involving photoreceptor damage in RP. Further research is warranted to validate this putative association and clarify causation. Choriocapillaris imaging using OCTA may provide information to supplement structural OCT findings when evaluating subjects with RP in neuroprotective or regenerative clinical trials.

Detection of Optic Disc Abnormalities in Color Fundus Photographs Using Deep Learning.

BACKGROUND: To date, deep learning-based detection of optic disc abnormalities in color fundus photographs has mostly been limited to the field of glaucoma. However, many life-threatening systemic and neurological conditions can manifest as optic disc abnormalities. In this study, we aimed to extend the application of deep learning (DL) in optic disc analyses to detect a spectrum of nonglaucomatous optic neuropathies. METHODS: Using transfer learning, we trained a ResNet-152 deep convolutional neural network (DCNN) to distinguish between normal and abnormal optic discs in color fundus photographs (CFPs). Our training data set included 944 deidentified CFPs (abnormal 364; normal 580). Our testing data set included 151 deidentified CFPs (abnormal 71; normal 80). Both the training and testing data sets contained a wide range of optic disc abnormalities, including but not limited to ischemic optic neuropathy, atrophy, compressive optic neuropathy, hereditary optic neuropathy, hypoplasia, papilledema, and toxic optic neuropathy. The standard measures of performance (sensitivity, specificity, and area under the curve of the receiver operating characteristic curve (AUC-ROC)) were used for evaluation. RESULTS: During the 10-fold cross-validation test, our DCNN for distinguishing between normal and abnormal optic discs achieved the following mean performance: AUC-ROC 0.99 (95 CI: 0.98-0.99), sensitivity 94% (95 CI: 91%-97%), and specificity 96% (95 CI: 93%-99%). When evaluated against the external testing data set, our model achieved the following mean performance: AUC-ROC 0.87, sensitivity 90%, and specificity 69%. CONCLUSION: In summary, we have developed a deep learning algorithm that is capable of detecting a spectrum of optic disc abnormalities in color fundus photographs, with a focus on neuro-ophthalmological etiologies. As the next step, we plan to validate our algorithm prospectively as a focused screening tool in the emergency department, which if successful could be beneficial because current practice pattern and training predict a shortage of neuro-ophthalmologists and ophthalmologists in general in the near future.

Performance and Limitation of Machine Learning Algorithms for Diabetic Retinopathy Screening: Meta-analysis.

BACKGROUND: Diabetic retinopathy (DR), whose standard diagnosis is performed by human experts, has high prevalence and requires a more efficient screening method. Although machine learning (ML)-based automated DR diagnosis has gained attention due to recent approval of IDx-DR, performance of this tool has not been examined systematically, and the best ML technique for use in a real-world setting has not been discussed. OBJECTIVE: The aim of this study was to systematically examine the overall diagnostic accuracy of ML in diagnosing DR of different categories based on color fundus photographs and to determine the state-of-the-art ML approach. METHODS: Published studies in PubMed and EMBASE were searched from inception to June 2020. Studies were screened for relevant outcomes, publication types, and data sufficiency, and a total of 60 out of 2128 (2.82%) studies were retrieved after study selection. Extraction of data was performed by 2 authors according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses), and the quality assessment was performed according to the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2). Meta-analysis of diagnostic accuracy was pooled using a bivariate random effects model. The main outcomes included diagnostic accuracy, sensitivity, and specificity of ML in diagnosing DR based on color fundus photographs, as well as the performances of different major types of ML algorithms. RESULTS: The primary meta-analysis included 60 color fundus photograph studies (445,175 interpretations). Overall, ML demonstrated high accuracy in diagnosing DR of various categories, with a pooled area under the receiver operating characteristic (AUROC) ranging from 0.97 (95% CI 0.96-0.99) to 0.99 (95% CI 0.98-1.00). The performance of ML in detecting more-than-mild DR was robust (sensitivity 0.95; AUROC 0.97), and by subgroup analyses, we observed that robust performance of ML was not limited to benchmark data sets (sensitivity 0.92; AUROC 0.96) but could be generalized to images collected in clinical practice (sensitivity 0.97; AUROC 0.97). Neural network was the most widely used method, and the subgroup analysis revealed a pooled AUROC of 0.98 (95% CI 0.96-0.99) for studies that used neural networks to diagnose more-than-mild DR. CONCLUSIONS: This meta-analysis demonstrated high diagnostic accuracy of ML algorithms in detecting DR on color fundus photographs, suggesting that state-of-the-art, ML-based DR screening algorithms are likely ready for clinical applications. However, a significant portion of the earlier published studies had methodology flaws, such as the lack of external validation and presence of spectrum bias. The results of these studies should be interpreted with caution.

[Effect of measurement sites on coronary computed tomography angiography-derived instantaneous wave-free ratio in the diagnosis of coronary stenosis ischemia].

Objective: To explore the influence of measurement sites on the diagnostic performance of coronary computed tomography angiography (CCTA) -derived instantaneous wave-free ratio (iFRCT) for coronary stenosis ischemia. Methods: A total of 44 patients, including 27 males and 17 females aged from 44 to 83 (59±90) years, who underwent coronary computed tomography angiography (CCTA) and invasive fractional flow reserve (FFR) in the Department of Radiology, Eastern Theater Command General Hospital from February 2009 to May 2018 were retrospectively collected. Based on CCTA images, iFRCT values at different locations (stenosis, proximal downstream of stenosis, 2 cm downstream of stenosis, 3 cm downstream of stenosis, and 4 cm downstream of stenosis) were calculated through fluid mechanics simulation. With invasive FFR≤0.80 as the reference standard, receiver operating characteristic (ROC) was used to analyze and evaluate the diagnostic performance of iFRCT in different sites. Bland-Altman and spearman correlation coefficient were used to analyze the consistency between iFRCT and invasive FFR. Intraclass correlation coefficient (ICC) and spearman correlation coefficient were used to test the repeatability of iFRCT. Results: iFRCT values at the proximal downstream of the stenosis (approximately 1 cm downstream of the stenosis) was superior to other measurement sites in the diagnosis of coronary ischemic specific stenosis. The threshold, area under the curve, sensitivity, specificity and accuracy of iFRCT at the stenosis were 0.91, 0.87 (95%CI:0.76~0.96), 82% (95%CI:48%~97%), 76% (95%CI:57%~88%) and 77% (95%CI: 63%~87%), respectively. Bland-Altman analysis showed that the mean differences between iFRCT and FFR at the proximal downstream of the stenosis was 0.07 (95%LoA: 0.06~0.09) and Spearman correlation coefficient was 0.53 (P<0.001). At the proximal downstream of the stenosis, the intraobserver ICC of iFRCT was 0.92 (95%CI: 0.85 ~0.95), the correlation coefficient was 0.85 (P<0.001); the interobserver ICC was 0.84 (95%CI: 0.60~0.94), correlation coefficient was 0.75 (P<0.001), demonstrating good repeatability between iFRCT and FFR. Conclusion: With the invasive FFR value as reference standard, iFRCT had a high diagnostic performance in detecting myocardial ischemia and the best measurement site was the proximal downstream of the stenosis.

[Association of coronary perivascular fat attenuation index, the parameters of plaque and fractional flow reserve].

Objective: To explore the association of coronary perivascular fat attenuation index (FAI), the parameters of plaque and fractional flow reserve (FFR). Methods: A total of 113 patients (with 141 plaques) (78 males and 35 females, age from 40 to 83 years) with stable coronary artery disease were retrospectively collected from Jingling Hospital and Shanghai Sixth People's Hospital. All the patients underwent coronary CT angiography and invasive FFR examinations. The quantitative and qualitative parameters of plaque and vessel (such as the length and volume of plaque, the characteristics of plaque and high-risk plaque) and the FAI around the plaque were measured. The patients were divided into positive FAI group (n=46) and negative FAI group (n=66) according to the standard of whether the threshold of FAI≥ -70 HU. The quantitative indexes, including age, the length and volume of plaque, minimal lumen area (MLA) and FAI, as well as the qualitative indexed, including the characteristics of plaque, the number and characteristic of high-risk plaque and the number of patients and plaque with positive FFR were compared between the two groups. Further, logistic regression analysis was performed to analyze the correlation among myocardial ischemia, age, the length of plaque, minimal lumen area (MLA), FAI and so on. ROC curve was used for evaluating the performance of each parameter. Results: Compared to the negative FAI group, positive FAI group had lower MLA (2.00±1.33 mm2 vs 4.13±2.41 mm2, P<0.001). The proportion of patients and vessels with FFR<0.75 in positive FAI group were significantly higher than that in negative FAI group (21.3% vs 4.5%, P=0.006; 23.2% vs 8.2%, P=0.016). The FAI between high-risk plaque and non-high-risk plaque had no significant difference (21.2% vs 16.1%, P=0.451). FAI predicted myocardial ischemia (AUC=0.666, P=0.021) and significantly improved the prediction efficiency of complex model(0.915 vs 0.951,P=0.033). Conclusion: Lower MLA and higher incidence of myocardial ischemia were associated with patients with higher FAI. In addition, FAI has a certain prediction efficiency and can provide incremental value for the determination of myocardial ischemia.

Controversies in artificial intelligence.

PURPOSE OF REVIEW: To review four recent controversial topics arising from deep learning applications in ophthalmology. RECENT FINDINGS: The controversies of four recent topics surrounding deep learning applications in ophthalmology are discussed, including the following: lack of explainability, limited generalizability, potential biases and protection of patient confidentiality in large-scale data transfer. SUMMARY: These controversial issues spanning the domains of clinical medicine, public health, computer science, ethics and legal issues, are complex and likely will benefit from an interdisciplinary approach if artificial intelligence in ophthalmology is to succeed over the next decade.

Deep Learning and Transfer Learning for Optic Disc Laterality Detection: Implications for Machine Learning in Neuro-Ophthalmology.

BACKGROUND: Deep learning (DL) has demonstrated human expert levels of performance for medical image classification in a wide array of medical fields, including ophthalmology. In this article, we present the results of our DL system designed to determine optic disc laterality, right eye vs left eye, in the presence of both normal and abnormal optic discs. METHODS: Using transfer learning, we modified the ResNet-152 deep convolutional neural network (DCNN), pretrained on ImageNet, to determine the optic disc laterality. After a 5-fold cross-validation, we generated receiver operating characteristic curves and corresponding area under the curve (AUC) values to evaluate performance. The data set consisted of 576 color fundus photographs (51% right and 49% left). Both 30° photographs centered on the optic disc (63%) and photographs with varying degree of optic disc centration and/or wider field of view (37%) were included. Both normal (27%) and abnormal (73%) optic discs were included. Various neuro-ophthalmological diseases were represented, such as, but not limited to, atrophy, anterior ischemic optic neuropathy, hypoplasia, and papilledema. RESULTS: Using 5-fold cross-validation (70% training; 10% validation; 20% testing), our DCNN for classifying right vs left optic disc achieved an average AUC of 0.999 (±0.002) with optimal threshold values, yielding an average accuracy of 98.78% (±1.52%), sensitivity of 98.60% (±1.72%), and specificity of 98.97% (±1.38%). When tested against a separate data set for external validation, our 5-fold cross-validation model achieved the following average performance: AUC 0.996 (±0.005), accuracy 97.2% (±2.0%), sensitivity 96.4% (±4.3%), and specificity 98.0% (±2.2%). CONCLUSIONS: Small data sets can be used to develop high-performing DL systems for semantic labeling of neuro-ophthalmology images, specifically in distinguishing between right and left optic discs, even in the presence of neuro-ophthalmological pathologies. Although this may seem like an elementary task, this study demonstrates the power of transfer learning and provides an example of a DCNN that can help curate large medical image databases for machine-learning purposes and facilitate ophthalmologist workflow by automatically labeling images according to laterality.

Application of Hollow Fiber Ultrafiltration Technology in the Detection of Total IgE of Hemolytic Blood after Death.

ABSTRACT: Objective To investigate the treatment effect of hollow fiber ultrafiltration technology on hemolytic samples and the differences between IgE concentration and serum concentration before hemolysis in ultrafiltrate. Methods The 33 postmortem blood samples of non-frozen corpses within 72 hours after death were collected, 4 mL blood was taken from each case, among which 1 mL was centrifuged to get serum, and the remaining 3 mL blood was frozen-thawed 3-5 times to cause complete hemolysis. The 2 mL hemolytic samples were processed by hollow fiber ultrafiltration to obtain ultrafiltrate. The hemoglobin concentration in serum, complete hemolytic sample and ultrafiltrate was determined by Van-Zij solution-cyanated methemoglobin assay method, and the total IgE in serum and ultrafiltrate was determined by electrochemical luminescence method. Results The hemoglobin concentration in ultrafiltrate was significantly lower than that in complete hemolytic samples （P<0.05）. There was a good correlation between the total IgE detection values of ultrafiltrate and serum （r=0.984）. The difference between the serum and the value of IgE in ultrafiltrate after correction had no statistical significance, and the differences between the two in positive rates had no statistical significance （P>0.05）. Conclusion Ultrafiltration technology has a good treatment effect on complete hemolytic samples, and the correction value of ultrafiltrate detection is close to the serum level before hemolysis, and therefore, it can be applied to the detection of total IgE of frozen corpse hemolytic samples.

A connection between the maximum displacements of rogue waves and the dynamics of poles in the complex plane.

Rogue waves of evolution systems are displacements which are localized in both space and time. The locations of the points of maximum displacements of the wave profiles may correlate with the trajectories of the poles of the exact solutions from the perspective of complex variables through analytic continuation. More precisely, the location of the maximum height of the rogue wave in laboratory coordinates (real space and time) is conjectured to be equal to the real part of the pole of the exact solution, if the spatial coordinate is allowed to be complex. This feature can be verified readily for the Peregrine breather (lowest order rogue wave) of the nonlinear Schrödinger equation. This connection is further demonstrated numerically here for more complicated scenarios, namely the second order rogue wave of the Boussinesq equation (for bidirectional long waves in shallow water), an asymmetric second order rogue wave for the nonlinear Schrödinger equation (as evolution system for slowly varying wave packets), and a symmetric second order rogue wave of coupled Schrödinger systems. Furthermore, the maximum displacements in physical space occur at a time instant where the trajectories of the poles in the complex plane reverse directions. This property is conjectured to hold for many other systems, and will help to determine the maximum amplitudes of rogue waves.

Frequent PD-L1 expression in primary and metastatic penile squamous cell carcinoma: potential opportunities for immunotherapeutic approaches.

BACKGROUND: Despite aggressive multimodal therapy, locally advanced and/or metastatic penile squamous cell carcinoma (SqCC) is associated with significant morbidity and mortality, indicating a need for new therapeutic options. Given the emerging clinical utility of immunotherapeutics, we sought to assess the incidence and potential clinical significance of PD-L1 expression in penile SqCC. PATIENTS AND METHODS: Using an anti-PD-L1 primary antibody (clone 5H1), immunohistochemistry was carried out on whole tumor sections from 37 patients with penile SqCC treated at our institution between 2005 and 2013. PD-L1-positive tumors were defined as those with membranous staining in ≥5% of tumor cells. Association between PD-L1 expression and clinicopathologic parameters was examined using Fisher's exact test. Correlation between PD-L1 expression in primary tumors and matched metastases was assessed using the Spearman rank correlation coefficient (ρ). The difference in cancer-specific mortality between PD-L1-positive and -negative groups was examined using the log-rank test. RESULTS: Twenty-three (62.2%) of 37 primary tumors were positive for PD-L1 expression, and there was strong positive correlation of PD-L1 expression in primary and metastatic samples (ρ = 0.72; 0.032 < P < 0.036). Primary tumor PD-L1 expression was significantly associated with usual type histology (P = 0.040) and regional lymph node metastasis (P = 0.024), as well as decreased cancer-specific survival (P = 0.011). CONCLUSIONS: The majority of primary penile SqCC tumors express PD-L1, which is associated with high-risk clinicopathologic features and poor clinical outcome. These data provide a rational basis for further investigation of anti-PD-1 and anti-PD-L1 immunotherapeutics in patients with advanced penile SqCC.