The transcription factor EBF1 non-cell-autonomously regulates cardiac growth and differentiation.

Reciprocal interactions between non-myocytes and cardiomyocytes regulate cardiac growth and differentiation. Here, we report that the transcription factor Ebf1 is highly expressed in non-myocytes and potently regulates heart development. Ebf1-deficient hearts display myocardial hypercellularity and reduced cardiomyocyte size, ventricular conduction system hypoplasia, and conduction system disease. Growth abnormalities in Ebf1 knockout hearts are observed as early as embryonic day 13.5. Transcriptional profiling of Ebf1-deficient embryonic cardiac non-myocytes demonstrates dysregulation of Polycomb repressive complex 2 targets, and ATAC-Seq reveals altered chromatin accessibility near many of these same genes. Gene set enrichment analysis of differentially expressed genes in cardiomyocytes isolated from E13.5 hearts of wild-type and mutant mice reveals significant enrichment of MYC targets and, consistent with this finding, we observe increased abundance of MYC in mutant hearts. EBF1-deficient non-myocytes, but not wild-type non-myocytes, are sufficient to induce excessive accumulation of MYC in co-cultured wild-type cardiomyocytes. Finally, we demonstrate that BMP signaling induces Ebf1 expression in embryonic heart cultures and controls a gene program enriched in EBF1 targets. These data reveal a previously unreported non-cell-autonomous pathway controlling cardiac growth and differentiation.

Neural cell adhesion molecule is required for ventricular conduction system development.

The most distal portion of the ventricular conduction system (VCS) contains cardiac Purkinje cells (PCs), which are essential for synchronous activation of the ventricular myocardium. Contactin-2 (CNTN2), a member of the immunoglobulin superfamily of cell adhesion molecules (IgSF-CAMs), was previously identified as a marker of the VCS. Through differential transcriptional profiling, we discovered two additional highly enriched IgSF-CAMs in the VCS: NCAM-1 and ALCAM. Immunofluorescence staining showed dynamic expression patterns for each IgSF-CAM during embryonic and early postnatal stages, but ultimately all three proteins became highly enriched in mature PCs. Mice deficient in NCAM-1, but not CNTN2 or ALCAM, exhibited defects in PC gene expression and VCS patterning, as well as cardiac conduction disease. Moreover, using ST8sia2 and ST8sia4 knockout mice, we show that inhibition of post-translational modification of NCAM-1 by polysialic acid leads to disrupted trafficking of sarcolemmal intercalated disc proteins to junctional membranes and abnormal expansion of the extracellular space between apposing PCs. Taken together, our data provide insights into the complex developmental biology of the ventricular conduction system.

Quantitative imaging for predicting hematoma expansion in intracerebral hemorrhage: A multimodel comparison.

BACKGROUND: Several studies report that radiomics provides additional information for predicting hematoma expansion in intracerebral hemorrhage (ICH). However, the comparison of diagnostic performance of radiomics for predicting revised hematoma expansion (RHE) remains unclear. METHODS: The cohort comprised 312 consecutive patients with ICH. A total of 1106 radiomics features from seven categories were extracted using Python software. Support vector machines achieved the best performance in both the training and validation datasets. Clinical factors models were constructed to predict RHE. Receiver operating characteristic curve analysis was used to assess the abilities of non-contrast computed tomography (NCCT) signs, radiomics features, and combined models to predict RHE. RESULTS: We finally selected the top 21 features for predicting RHE. After univariate analysis, 4 clinical factors and 5 NCCT signs were selected for inclusion in the prediction models. In the training and validation dataset, radiomics features had a higher predictive value for RHE (AUC = 0.83) than a single NCCT sign and expansion-prone hematoma. The combined prediction model including radiomics features, clinical factors, and NCCT signs achieved higher predictive performances for RHE (AUC = 0.88) than other combined models. CONCLUSIONS: NCCT radiomics features have a good degree of discrimination for predicting RHE in ICH patients. Combined prediction models that include quantitative imaging significantly improve the prediction of RHE, which may assist in the risk stratification of ICH patients for anti-expansion treatments.

[Exploration and example interpretation of real-world herbal prescription classification based on similarity matching algorithm].

In observational studies, herbal prescriptions are usually studied in the form of "similar prescriptions". At present, the classification of prescriptions is mainly based on clinical experience judgment, but there are some problems in manual judgment, such as lack of unified criteria, labor consumption, and difficulty in verification. In the construction of a database of integrated traditional Chinese and western medicine for the treatment of coronavirus disease 2019(COVID-19), our research group tried to classify real-world herbal prescriptions using a similarity matching algorithm. The main steps include 78 target prescriptions are determined in advance; four levels of importance labeling shall be carried out for the drugs of each target prescription; the combination, format conversion, and standardization of drug names of the prescriptions to be identified in the herbal medicine database; calculate the similarity between the prescriptions to be identified and each target prescription one by one; prescription discrimination is performed based on the preset criteria; remove the name of the prescriptions with "large prescriptions cover the small". Through the similarity matching algorithm, 87.49% of the real prescriptions in the herbal medicine database of this study can be identified, which preliminarily proves that this method can complete the classification of herbal prescriptions. However, this method does not consider the influence of herbal dosage on the results, and there is no recognized standard for the weight of drug importance and criteria, so there are some limitations, which need to be further explored and improved in future research.

Quantitative analysis of branching neovascular networks in polypoidal choroidal vasculopathy by optical coherence tomography angiography after photodynamic therapy and anti-vascular endothelial growth factor combination therapy.

PURPOSE: To study serial changes in branching neovascular networks (BNN) by using optical coherence tomography angiography (OCTA) in patients with polypoidal choroidal vasculopathy (PCV) who underwent combined photodynamic therapy (PDT) and anti-vascular endothelial growth factor (anti-VEGF) therapy. METHODS: In this retrospective study of 30 PCV patients who underwent combined therapy, OCTA images obtained at baseline and 1, 3, and 6 months after treatment were collected. The vessel area, vessel percentage area, average vessel length, and presence of polypoidal lesions on OCTA images as well as best-corrected visual acuity (BCVA), central retinal thickness (CRT), and central choroidal thickness (CCT) were recorded at each time point. RESULTS: The BNN- and polypoidal lesion-detection rates on baseline OCTA images were 100% and 71%, respectively. The vessel area decreased during the first 3 months, and increased 6 months post-treatment, showing significant differences from baseline (p = 0.031). The vessel percentage area also reduced 1 and 3 months post-treatment (p = 0.025) and increased 6 months post-treatment. Continuous polypoidal lesion regression was observed from 1 to 3 and 6 months post-treatment (p = 0.031, p = 0.004, p = 0.002, respectively, in comparison with baseline). Patients with a decreasing vessel area over 6 months showed greater choroidal thickness than those with increasing vessel area (p = 0.004). CONCLUSIONS: The BNN showed initial regression but were enlarged at 6 months after therapy. Patients showing continuous BNN regression showed a thicker choroid at baseline. This difference should be considered during treatment for PCV, and OCTA could be used for follow-up evaluations of PCV patients.

Surgical and Anatomic Consideration in Endoscopic Dacryocystorhinostomy of a Patient with Damaged Sinonasal Anatomy Post-Caldwell-Luc Surgery: A Case Report.

Background: The Caldwell-Luc (CL) procedure, an outdated operative procedure that is used to treat inflammatory sinus diseases, is rarely performed presently. However, physicians may encounter patients with a history of CL surgery who develop considerable postoperative changes that may lead to diagnostic confusion in imaging evaluation; increase the difficulty of future surgery, such as sinonasal surgery; and increase the incidence of future intraoperative complications. Case summary: A 67-year-old man with a surgical history of chronic sinusitis reported epiphora of the left eye for five years. Balloon dacryocystoplasty was attempted but failed. Endo-DCR (Endoscopic dacryocystorhinostomy) was indicated; however, preoperative CT (computed tomography) imaging and nasal endoscopic examination showed sinonasal anomalies and the loss of internal landmarks for localizing the lacrimal sac. Preoperative CT results indicated previous CL surgery. Endo-DCR was performed with the aid of nasal forceps and a 20-gauge vitreoretinal fiberoptic endoilluminator. A six-month follow-up revealed the complete resolution of symptoms and no signs of recurrence. Conclusions: Epiphora might be a delayed complication of the CL procedure. Before performing endo-DCR, ophthalmologists should be familiar with the sinonasal anatomy and carefully assess preoperative imaging to identify anatomical variations. Nasal forceps and transcanalicular illumination can assist in determining the precise location of the lacrimal sac during endo-DCR.

Adjuvant Intravitreal Bevacizumab Injection for Choroidal and Orbital Metastases of Refractory Invasive Ductal Carcinoma of the Breast.

The efficacy of combined intravitreal bevacizumab injection with systemic chemotherapy, palliative radiotherapy, and hormonal therapy to treat choroidal and orbital metastases is not known. Herein, we report the case of a 48-year-old woman with systemic chemotherapy-resistant choroidal and orbital metastases of the left eye originating from a stage IV invasive ductal carcinoma of the left breast. We describe the addition of a single intravitreal injection of bevacizumab in addition to treatment with systemic chemotherapy, hormonal therapy, and palliative radiotherapy. The patient's outcome at 6-month follow-up was favorable, as the metastatic lesion reduced in size and visual acuity improved. Combined treatment with intravitreal bevacizumab injection, systemic chemotherapy, palliative radiotherapy, and hormonal therapy can resolve ocular metastatic lesions originating from breast cancers.

A rare case of herniated duplex collecting system causing obstructive uropathy.

BACKGROUND: An inguinal hernia is the protrusion of intraabdominal organs through an opening in the abdominal wall. Structures such as small and large intestines are commonly contained within inguinal hernias. However, uretero-inguinal hernia of the native collecting system is an extremely rarely reported entity. If unrecognized, acute kidney injury due to obstructive uropathy or serious intraprocedural ureteral injuries during hernia repair can occur. A duplex collecting system is a congenital kidney anomaly with an incidence of 0.8%. A uretero-inguinal hernia involving duplicated ureters has not been previously described in literature. Here we report a case of obstructive uropathy secondary to uretero-inguinal hernia involving duplicated ureters. CASE PRESENTATION: A 78-year-old male known to have a left sided inguinal hernia presented to the Emergency department with two weeks of intermittent suprapubic tenderness, dysuria, frequency, urgency, frothy urine as well as nausea and vomiting. Workup on admission revealed an elevated creatinine of 2.8 mg/dl. CT imaging revealed duplicated left sided ureters with left inguinal hernia containing the ureters. There was cystic ureteral dilation within the herniation sac as well as moderate left hydroureteronephrosis. Patient had an elective inguinal hernia repair with left ureteral stent placement. Following the surgery, he had recovery of kidney function to the previous baseline serum creatinine of 1.5 mg/dl. CONCLUSION: A duplex collecting system arises when two ureteral buds are formed during fetal development. However, diagnosis can be made in rare instances during adulthood when duplex collecting systems are usually found incidentally. Uretero-inguinal hernias have been reported as a common complication of renal transplant. However, uretero-inguinal hernias in native kidneys are considered an uncommon finding, especially with a duplex collecting system. When patients present with herniation and acute kidney injury, it is important to rule out the possibility of uretero-inguinal hernia to minimize complications such as obstructive uropathy and kidney failure. CT scan providing cross-sectional imaging is the ideal modality for identification of the site and etiology of urinary tract obstruction and site of herniation. If during imaging, an obstructive uropathy is observed, a nephroureteral stent or nephrostomy tube can be inserted to protect the ureter as well as relieve the obstruction, respectively.

Bone marrow mesenchymal stem cells modified by angiogenin-1 promotes tissue repair in mice with oxygen-induced retinopathy of prematurity by promoting retinal stem cell proliferation and differentiation.

Retinopathy has become one of the major factors that lead to blindness worldwide. Although many clinical therapies are concerned about such disease, most of them focus on symptoms alleviation. In this study, we aim to investigate whether coculture retinal stem cells (RSCs) with bone marrow mesenchymal stem cells transfected with angiogenin-1 (Ang-1-BMSCs) affects the damaged retinal tissue of oxygen-induced retinopathy of prematurity (OIR-ROP) mice. After OIR-ROP mouse model establishment, Ang-1-BMSCs, RSCs, and OIR-ROP retinal tissues were cocultured in a a transwell chamber. RSCs proliferation and the expression of Ang-1, insulin-like growth factor-1 (IGF-1) in the supernatant of RSCs, as well as ß-tubulin and protein kinase C (PKC) expression were evaluated. Finally, the repair of OIR-ROP mice retinal tissues was observed by injecting Ang-1-BMSCs + RSCs. In the OIR-ROP mouse model, RSCs cocultured with OIR-ROP retinal tissues could be induced to differentiate into cells expressing ß-tubulin and PKC and promote the expression of Ang-1 and IGF-1. coculture of Ang-1-BMSCs further enhanced the proliferation and differentiation of RSCs by promoting the expression of Ang-1 and IGF-1. Coculture of RSCs + Ang-1-BMSCs induced differentiation of Ang-1-BMSCs through interaction among intercellular factors and restored the damaged retinal tissue of OIR-ROP mice. Collectively, our study provided evidence that coculture of Ang-1-BMSCs and RSCs could promote the proliferation and differentiation of RSCs and improve the treatment for the damaged retina tissue of OIR-ROP mice.

Dermatologic tacrolimus ointment on the eyelids for steroid-refractory vernal keratoconjunctivitis.

PURPOSE: The study aims to evaluate the therapeutic effects of dermatologic tacrolimus ointment on eyelids to treat refractory vernal keratoconjunctivitis (VKC). METHOD: This institutional study examined the effects of steroid treatment for 10 patients diagnosed with severe VKC refractory to steroid treatment. Patients received 0.1% dermatologic topical tacrolimus treatment on their eyelids once or twice daily for concomitant atopic dermatitis. The therapeutic outcomes were evaluated according to change in severity of clinical findings recorded with serial external ocular photography and change in requirement for steroid treatment. RESULTS: Clinical signs and symptoms improved substantially after tacrolimus treatment. Significant reduction in size of papillae, decrease of discharge, improvement in hyperemia, and shield ulcer healing with re-epithelization were observed in all patients. Six out of 10 (60%) patients did not receive steroid treatment. Long-term maintenance of tacrolimus was required to prevent episodic exacerbation. Patients' only treatment-related complaints were of mild burning sensations during medication application to eyelids, and this sensation disappeared a few days after treatment. CONCLUSIONS: Application of 0.1% dermatologic tacrolimus ointment to eyelids is effective and safe in the treatment of refractory VKC in patients with concomitant atopic dermatitis. This treatment may serve as a substitute for or decrease the requirement of steroid treatment.

[Nursing Experience of a Patient With Breast Cancer Who Suffered From a Fungating Wound].

This report discusses an experience of taking care of a breast cancer patient with rapidly deteriorating, fungating wounds and herpes simplex virus wounds and describes the physical and psychological effects on the patient and the related decreases in the quality of life of both the patient and her caregivers. Nursing care was implemented from December 14th, 2017 to January 23rd, 2018. Data collection was performed through direct caregiving, observation, interviews, and chart review. Three major problems were identified: difficulties with wound care, psychological distress of the patient, and the coping problems of the caregivers. Based on these problems, nursing interventions were implemented. During the period, fungating wound care guidelines were used to teach the patient and her caregivers the core principles of fungating wound management. Meanwhile, the COPE framework (creativity, optimism, planning, and expert information) was applied to train the patient and her caregivers how to develop problem-solving skills and build self-confidence. Finally, the patient and her family successfully overcame these challenges. The patient was relieved of stress and anxiety, became better able to self-manage her symptoms, sustain hope for the future, and improve her perception of body self-image. We suggested that the patient and her family be considered a single, supportive unit and then helped them cope with the disease and build self-care confidence in order to improve their life quality and to coexist with the disease. We hope that our clinical experience will be taken as a reference by patient caregivers.

Effects of bone marrow mesenchymal stem cells transfected with Ang-1 gene on hyperoxia-induced optic nerve injury in neonatal mice.

Optic nerve injury triggered retinal ganglion cell (RGC) death and optic nerve atrophy lead to visual loss. Bone marrow mesenchymal stem cells (BMSCs) are stromal cells, capable of proliferating and differentiating into different types of tissues. This aims of this study is to investigate the role of BMSCs transfected with angiopoietin-1 (Ang-1) in optic nerve injury induced by hyperoxia in a neonatal mice model. Ang-1 overexpression vector was constructed and used to transfect BMSCs. Reverse transcription-quantitative polymerase chain reaction was performed to detect Ang-1 expression in BMSCs. The hyperoxia-induced optic nerve injury model was established. The optic nerves at 6-7 mm posterior to the eyeball were extracted, and were treated with luxol fast blue staining, immunohistochemistry, immunofluorescence, and transmission electron microscopy to examine the effects of Ang-1-modified BMSCs on optic nerve injury induced by hyperoxia. The mice in the Ang-1 + BMSCs and BMSCs groups showed remarkably improved myelin sheaths of nerve fibers compared to the hyperoxia saline group. The positive expression and integrated optic density of Ang-1 in the Ang-1 + BMSCs group were significantly higher compared to the air control, hyperoxia saline and BMSCs groups. The number and diameter of myelinated nerve fibers, the diameter of axons and the thickness of myelin sheath in the air control and Ang-1 + BMSCs groups were higher compared to the hyperoxia saline group. Our study provides evidence supporting that Ang-1-modified BMSCs may have preventive and therapeutic effects on hyperoxia-induced optic nerve injury in neonatal mice.

Phosphatase-resistant gap junctions inhibit pathological remodeling and prevent arrhythmias.

RATIONALE: Posttranslational phosphorylation of connexin43 (Cx43) has been proposed as a key regulatory event in normal cardiac gap junction expression and pathological gap junction remodeling. Nonetheless, the role of Cx43 phosphorylation in the context of the intact organism is poorly understood. OBJECTIVE: To establish whether specific Cx43 phosphorylation events influence gap junction expression and pathological remodeling. METHODS AND RESULTS: We generated Cx43 germline knock-in mice in which serines 325/328/330 were replaced with phosphomimetic glutamic acids (S3E) or nonphosphorylatable alanines (S3A). The S3E mice were resistant to acute and chronic pathological gap junction remodeling and displayed diminished susceptibility to the induction of ventricular arrhythmias. Conversely, the S3A mice showed deleterious effects on cardiac gap junction formation and function, developed electric remodeling, and were highly susceptible to inducible arrhythmias. CONCLUSIONS: These data demonstrate a mechanistic link between posttranslational phosphorylation of Cx43 and gap junction formation, remodeling, and arrhythmic susceptibility.

Purkinje cells from RyR2 mutant mice are highly arrhythmogenic but responsive to targeted therapy.

RATIONALE: The Purkinje fiber network has been proposed as the source of arrhythmogenic Ca(2+) release events in catecholaminergic polymorphic ventricular tachycardia (CPVT), yet evidence supporting this mechanism at the cellular level is lacking. OBJECTIVE: We sought to determine the frequency and severity of spontaneous Ca(2+) release events and the response to the antiarrhythmic agent flecainide in Purkinje cells and ventricular myocytes from RyR2(R4496C/+) CPVT mutant mice and littermate controls. METHODS AND RESULTS: We crossed RyR2(R4496C/+) knock-in mice with the newly described Cntn2-EGFP BAC transgenic mice, which express a fluorescent reporter gene in cells of the cardiac conduction system, including the distal Purkinje fiber network. Isolated ventricular myocytes (EGFP(-)) and Purkinje cells (EGFP(+)) from wild-type hearts and mutant hearts were distinguished by epifluorescence and intracellular Ca(2+) dynamics recorded by microfluorimetry. Both wild-type and RyR2(R4496C/+) mutant Purkinje cells displayed significantly slower kinetics of activation and relaxation compared to ventricular myocytes of the same genotype, and tau(decay) in the mutant Purkinje cells was significantly slower than that observed in wild-type Purkinje cells. Of the 4 groups studied, RyR2(R4496C/+) mutant Purkinje cells were also most likely to develop spontaneous Ca(2+) release events, and the number of events per cell was also significantly greater. Furthermore, with isoproterenol treatment, although all 4 groups showed increases in the frequency of arrhythmogenic Ca(2+(i)) events, the RyR2(R4496C/+) Purkinje cells responded with the most profound abnormalities in intracellular Ca(2+) handling, including a significant increase in the frequency of unstimulated Ca(2+(i)) events and the development of alternans, as well as isolated and sustained runs of triggered beats. Both Purkinje cells and ventricular myocytes from wild-type mice showed suppression of spontaneous Ca(2+) release events with flecainide, whereas in RyR2(R4496C/+) mice, the Purkinje cells were preferentially responsive to drug. In contrast, the RyR2 blocker tetracaine was equally efficacious in mutant Purkinje cells and ventricular myocytes. CONCLUSIONS: Purkinje cells display a greater propensity to develop abnormalities in intracellular Ca(2+) handling than ventricular myocytes. This proarrhythmic behavior is enhanced by disease-causing mutations in the RyR2 Ca(2+) release channel and greatly exacerbated by catecholaminergic stimulation, with the development of arrhythmogenic triggered beats. These data support the concept that Purkinje cells are critical contributors to arrhythmic triggers in animal models and humans with CPVT and suggest a broader role for the Purkinje fiber network in the genesis of ventricular arrhythmias.

Effective nonlinear responses of three-phase magnetoelectric composites.

A computational method, dubbed simplified unit-cell micromechanics model, is generalized and applied to establish the effective nonlinear responses of three-phase magnetoelectric composites that are composed of two distinct magnetostrictive and piezoelectric phases embedded in elastic polymer matrices. The nature of nonlinear constitutive behavior of each constituent is expected to significantly influence the overall responses of the composites. To obtain the effective nonlinear responses, a mathematical linearization is first introduced to perform the constitutive linearization for the nonlinear materials, and the resulting constitutive equations are then unified and nested into the micromechanics model followed by iterations in order to minimize errors from the linearization process. For the purpose of comparison, we also reformulate the well-established Mori-Tanaka micromechanics model insofar as its mathematical structure is aligned with that of the simplified unit-cell model. Numerical results are first validated against limited experimental measurements available in literature. Parametric studies are then conducted in order to reveal the effect of phase constitutive laws, volume fractions, and geometries on the overall nonlinear responses of there-phase magnetoelectric composites. The contributions of this work complement those of earlier studies that prevalently devoted to two-phase magnetoelectric composites and linear magneto-electro-elastic coupled responses only.

A case of herpes simplex 2 encephalitis with an unusual radiographic manifestation.

Herpes Simplex Virus (HSV) continues to be an important pathogen inflicting encephalitis in adults and children globally that entails high morbidity and mortality. Prompt diagnosis and treatment are the keys to minimize potential sequelae of the disease. Although HSV encephalitis-1(HSVE-1) is well recognized for its radiographic manifestation of temporal lobe involvement owing to its pathogenesis, radiographic features of HSVE-2 are less uniform. Lumbar puncture with HSV PCR testing is the gold standard for diagnosis. However, when lumbar puncture is not immediately obtainable, consideration of HSVE should be entertained in compatible clinical setting even in the absence of characteristic radiographic finding. We report a case of type 2 HSVE with atypical radiographic manifestation involving bilateral basal ganglia.

[Exploration on the rules of acupoints selection for phlegm disorder treated with acupuncture and moxibustion based on ancient literature study].

OBJECTIVE: To analyze the rules of acupoints selection for phlegm disorder in treatment with acupuncture and moxibustion in ancient literature so as to provide guidance to clinical treatment of phlegm disorder. METHODS: The word "phlegm" was taken as the search term and the relevant articles were retrieved from Zhonghuayidian (Dictionary of Chinese Medicine). According to the inclusion and exclusion criteria, the articles were screened and the database was set up. The analysis was conducted on acupoint selection, the correlation with meridians involved and distribution location, as well as the use frequency of specific points and acupoint combination. RESULTS: It was found that in treatment of phlegm disorder, the highest frequently used acupoints were Zusanli (ST36) and Zhongwan (CV12). The use frequency of three yang meridians was higher than that of three yin meridians. The commonly involved meridians were the Conception Vessel, Bladder Meridian of Foot-taiyang and the Governor Vessel. The acupoints located in the chest and abdomen were highly used. The use frequency of specific points was higher than that of non-specific ones. The sequence of the use frequency of specific points, from high to low, is the crossing point, the front-mu point and luo-connecting point. The combination of Danzhong (CV17) and Zusanli (ST36) is of the high frequency. CONCLUSION: Ancient medical scholars focus on regulating spleen and stomach functions, as well as qi activity in treatment of phlegm disorder with acupuncture and moxibustion, which is coincident with the treatment principle of phlegm disorder in traditional Chinese medicine. In treatment, acupuncture-moxibusiton is characterized as laying the emphasis on the specific points, the local acupoints and the holistic idea as " regulation of yang for yin disorder"．.

Keratoconus Screening Based on Deep Learning Approach of Corneal Topography.

Purpose: To develop and compare deep learning (DL) algorithms to detect keratoconus on the basis of corneal topography and validate with visualization methods. Methods: We retrospectively collected corneal topographies of the study group with clinically manifested keratoconus and the control group with regular astigmatism. All images were divided into training and test datasets. We adopted three convolutional neural network (CNN) models for learning. The test dataset was applied to analyze the performance of the three models. In addition, for better discrimination and understanding, we displayed the pixel-wise discriminative features and class-discriminative heat map of diopter images for visualization. Results: Overall, 170 keratoconus, 28 subclinical keratoconus and 156 normal topographic pictures were collected. The convergence of accuracy and loss for the training and test datasets after training revealed no overfitting in all three CNN models. The sensitivity and specificity of all CNN models were over 0.90, and the area under the receiver operating characteristic curve reached 0.995 in the ResNet152 model. The pixel-wise discriminative features and the heat map of the prediction layer in the VGG16 model both revealed it focused on the largest gradient difference of topographic maps, which was corresponding to the diagnostic clues of ophthalmologists. The subclinical keratoconus was positively predicted with our model and also correlated with topographic indexes. Conclusions: The DL models had fair accuracy for keratoconus screening based on corneal topographic images. The visualization mentioned in the current study revealed that the model focused on the appropriate region for diagnosis and rendered clinical explainability of deep learning more acceptable. Translational Relevance: These high accuracy CNN models can aid ophthalmologists in keratoconus screening with color-coded corneal topography maps.

Quantitative Physical Fitness Measures Inversely Associated With Myopia Severity in Military Males: The CHIEF Study.

Myopia has been linked to body weight and sedentary status, but the association with quantitatively measured physical fitness in adults has not been examined. Cross-sectional analyses were performed to investigate the association between physical fitness and myopia in 3,669 military men (aged 29.4 years) in Taiwan. The severity of myopia obtained from the left eye was classified as mild (-0.5 to -3.0 diopters; n = 544), moderate -3.1 to -6.0 diopters; n = 563), and high (<-6.0 diopters; n =150); others were defined as nonmyopia (n = 2,412). Aerobic fitness was evaluated by time for a 3000-meter run test, and muscular endurance was evaluated by numbers of 2-min sit-ups and 2-min push-ups. A value of p < .0125 was considered significant. A multiple linear regression analysis was used to determine the relationship. Individuals who were less physically fit had higher risk of myopia. The associations were dose-dependently significant with mild, moderate, and high myopia for 3000-meter running time (ß = 9.64; 95% confidence intervals [3.22, 16.05], ß = 12.41; 95% CI [6.05, 18.76], and ß = 20.87; 95% CI [9.22, 32.51], respectively) after controlling for the potential covariates. There tended to be an inverse association with moderate and high myopia for numbers of 2-min push-ups (ß = -1.38; 95% CI [-2.43, -0.34] and ß = -2.10; 95% CI [- 3.97, -0.22], respectively) and 2-min sit-ups (ß = -0.83; 95% CI [-1.54, -0.12] and ß = -1.29; 95% CI [-2.56, -0.02], respectively), respectively. This study suggested that physical fitness, particularly aerobic fitness of the military males who received regular training, is inversely associated with myopia severity, independent of service specialty, body mass index, and educational level.

Uncovering the regeneration strategies of zebrafish organs: a comprehensive systems biology study on heart, cerebellum, fin, and retina regeneration.

BACKGROUND: Regeneration is an important biological process for the restoration of organ mass, structure, and function after damage, and involves complex bio-physiological mechanisms including cell differentiation and immune responses. We constructed four regenerative protein-protein interaction (PPI) networks using dynamic models and AIC (Akaike's Information Criterion), based on time-course microarray data from the regeneration of four zebrafish organs: heart, cerebellum, fin, and retina. We extracted core and organ-specific proteins, and proposed a recalled-blastema-like formation model to uncover regeneration strategies in zebrafish. RESULTS: It was observed that the core proteins were involved in TGF-ß signaling for each step in the recalled-blastema-like formation model and TGF-ß signaling may be vital for regeneration. Integrins, FGF, and PDGF accelerate hemostasis during heart injury, while Bdnf shields retinal neurons from secondary damage and augments survival during the injury response. Wnt signaling mediates the growth and differentiation of cerebellum and fin neural stem cells, potentially providing a signal to trigger differentiation. CONCLUSION: Through our analysis of all four zebrafish regenerative PPI networks, we provide insights that uncover the underlying strategies of zebrafish organ regeneration.