Exploration on OCT biomarker candidate related to macular edema caused by diabetic retinopathy and retinal vein occlusion in SD-OCT images.

To improve the understanding of potential pathological mechanisms of macular edema (ME), we try to discover biomarker candidates related to ME caused by diabetic retinopathy (DR) and retinal vein occlusion (RVO) in spectral-domain optical coherence tomography images by means of deep learning (DL). 32 eyes of 26 subjects with non-proliferative DR (NPDR), 77 eyes of 61 subjects with proliferative DR (PDR), 120 eyes of 116 subjects with branch RVO (BRVO), and 17 eyes of 15 subjects with central RVO (CRVO) were collected. A DL model was implemented to guide biomarker candidate discovery. The disorganization of the retinal outer layers (DROL), i.e., the gray value of the retinal tissues between the external limiting membrane (ELM) and retinal pigment epithelium (RPE), the disrupted and obscured rate of the ELM, ellipsoid zone (EZ), and RPE, was measured. In addition, the occurrence, number, volume, and projected area of hyperreflective foci (HRF) were recorded. ELM, EZ, and RPE are more likely to be obscured in RVO group and HRFs are observed more frequently in DR group (all P ≤ 0.001). In conclusion, the features of DROL and HRF can be possible biomarkers related to ME caused by DR and RVO in OCT modality.

Assessment of the antimicrobial and immunomodulatory activity of QS-CATH, a promising therapeutic agent isolated from the Chinese spiny frogs (Quasipaa spinosa).

Cathelicidins are important antimicrobial peptides in various vertebrate species where they are crucial parts of the innate immune system. The current understanding of amphibian cathelicidins is limited, particularly with regard to their immunomodulatory effects. To address this knowledge gap, we produced the cDNA sequence of the cathelicidin gene from a skin transcriptome of the Chinese spiny frog Quasipaa spinosa. The amino acid sequence of the Quasipaa spinosa cathelicidin (QS-CATH) was predicted to consist of a signal peptide, a cathelin domain, and a mature peptide. Comparative analysis of the QS-CATH amino acid sequence with that of other amphibian cathelicidins revealed high variability in the functional mature peptide among amphibians, whereas the cathelin domain was conserved. The QS-CATH gene was expressed in several tissues, with the highest level of expression in the spleen. Upregulation of QS-CATH after Aeromonas hydrophila infection occurred in the kidney, gut, spleen, skin, and liver. Chemically synthesized QS-CATH exhibited pronounced antibacterial activity against Shigella flexneri, Staphylococcus warneri, Escherichia coli, Salmonella enterica, and Listeria monocytogenes. Furthermore, QS-CATH disrupted the cell membrane integrity of S. flexneri, as evidenced by a lactate dehydrogenase release assay, and it hydrolyzed the genomic DNA of S. flexneri. Additionally, QS-CATH elicited chemotaxis and modulated the expression of inflammatory cytokine genes in RAW264.7 mouse leukemic monocyte/macrophage cells. These findings confirm the antimicrobial effects of amphibian cathelicidin and its ability to influence immune cell function. This will expedite the potential utilization of amphibian antimicrobial peptides as therapeutic agents.

Transcriptomic analysis of skin immunity genes in the Chinese spiny frog (Quasipaa spinosa) after Proteus mirabilis infection.

Recently, populations of Chinese spiny frogs (Quasipaa spinosa), an important amphibian species in China, have decreased, mainly due to a disease caused by the gram-negative bacteria Proteus mirabilis. To elucidate the immune response of the frogs, this study aimed to identify novel candidate genes functionally associated with P. mirabilis infection-induced "rotting skin" disease. Chinese spiny frogs were infected with P. mirabilis, and the skin transcriptome was sequenced using the MGISEQ-2000 platform. A total of 233,965 unigenes were obtained by sequencing, of which 27.23 % were known genes. Screening of differentially expressed genes (DEGs) indicated 210 unigenes differentially expressed after P. mirabilis infection, of which 132 unigenes were up-regulated, and 78 unigenes were down-regulated. Using Kyoto Encyclopedia of Genes and Genomes enrichment analysis, DEGs were identified as enriched in signal pathways, such as oxidative phosphorylation, apoptosis, and the Janus kinase-signal transducer and activator of transcription pathway. Of the DEGs, there was a significant upregulation of the colony stimulating factor 2 receptor beta common subunit, interleukin 2 receptor subunit gamma, cathelicidin antimicrobial peptide, interleukin-17 receptor E, receptor-interacting serine/threonine-protein kinase 3, and pulmonary surfactant-associated protein D immune genes following P. mirabilis infection. Conversely, scavenger receptor cysteine-rich domain-containing group B protein, tumor protein p53 inducible nuclear protein 2, suppressor of cytokine signaling 2, and metalloreductase STEAP3 were significantly downregulated. In conclusion, the first skin transcriptome database of Chinese spiny frogs was established, and several immune genes were identified to elucidate the pathogenic mechanism of "skin rot" in Chinese spiny frogs and other cultured frogs.

TestFit: A plug-and-play one-pass test time method for medical image segmentation.

Deep learning (DL) based methods have been extensively studied for medical image segmentation, mostly emphasizing the design and training of DL networks. Only few attempts were made on developing methods for applying DL models in test time. In this paper, we study whether a given off-the-shelf segmentation network can be stably improved on-the-fly during test time in an online processing-and-learning fashion. We propose a new online test-time method, called TestFit, to improve results of a given off-the-shelf DL segmentation model in test time by actively fitting the test data distribution. TestFit first creates a supplementary network (SuppNet) from the given trained off-the-shelf segmentation network (this original network is referred to as OGNet) and applies SuppNet together with OGNet for test time inference. OGNet keeps its hypothesis derived from the original training set to prevent the model from collapsing, while SuppNet seeks to fit the test data distribution. Segmentation results and supervision signals (for updating SuppNet) are generated by combining the outputs of OGNet and SuppNet on the fly. TestFit needs only one pass on each test sample - the same as the traditional test model pipeline - and requires no training time preparation. Since it is challenging to look at only one test sample and no manual annotation for model update each time, we develop a series of technical treatments for improving the stability and effectiveness of our proposed online test-time training method. TestFit works in a plug-and-play fashion, requires minimal hyper-parameter tuning, and is easy to use in practice. Experiments on a large collection of 2D and 3D datasets demonstrate the capability of our TestFit method.

LAGAN: Lesion-Aware Generative Adversarial Networks for Edema Area Segmentation in SD-OCT Images.

Large volume of labeled data is a cornerstone for deep learning (DL) based segmentation methods. Medical images require domain experts to annotate, and full segmentation annotations of large volumes of medical data are difficult, if not impossible, to acquire in practice. Compared with full annotations, image-level labels are multiple orders of magnitude faster and easier to obtain. Image-level labels contain rich information that correlates with the underlying segmentation tasks and should be utilized in modeling segmentation problems. In this article, we aim to build a robust DL-based lesion segmentation model using only image-level labels (normal v.s. abnormal). Our method consists of three main steps: (1) training an image classifier with image-level labels; (2) utilizing a model visualization tool to generate an object heat map for each training sample according to the trained classifier; (3) based on the generated heat maps (as pseudo-annotations) and an adversarial learning framework, we construct and train an image generator for Edema Area Segmentation (EAS). We name the proposed method Lesion-Aware Generative Adversarial Networks (LAGAN) as it combines the merits of supervised learning (being lesion-aware) and adversarial training (for image generation). Additional technical treatments, such as the design of a multi-scale patch-based discriminator, further enhance the effectiveness of our proposed method. We validate the superior performance of LAGAN via comprehensive experiments on two publicly available datasets (i.e., AI Challenger and RETOUCH).

Self-Supervised Sequence Recovery for Semi-Supervised Retinal Layer Segmentation.

Automated layer segmentation plays an important role for retinal disease diagnosis in optical coherence tomography (OCT) images. However, the severe retinal diseases result in the performance degeneration of automated layer segmentation approaches. In this paper, we present a robust semi-supervised layer segmentation network to relieve the model failures on abnormal retinas. We obtain the lesion features from the labeled images with disease-balanced distribution, and utilize the unlabeled images to supplement the layer structure information. Specifically, in our method, the cross-consistency training is utilized over the predictions of different decoders, and we enforce a consistency between different decoder predictions to improve the encoder's representation. Then, we propose a sequence prediction branch based on self-supervised manner, which is designed to predict the position of each jigsaw puzzle to obtain sensory perception of the retinal layer structure. To this task, a layer spatial pyramid pooling (LSPP) module is designed to extract multi-scale layer spatial features. Furthermore, we use the optical coherence tomography angiography (OCTA) to supplement the information damaged by diseases. The experimental results illustrate that our method achieves more robust results compared with current supervised segmentation methods. Meanwhile, advanced segmentation performance can be obtained compared with state-of-the-art semi-supervised segmentation methods.

Epidemiological study of hepatitis B and hepatitis C infections in Northeastern China and the beneficial effect of the vaccination strategy for hepatitis B: a cross-sectional study.

BACKGROUND: Viral hepatitis, mainly hepatitis B and C, is a serious public health problem worldwide. In China, the prevalence of hepatitis B virus (HBV) infection remains high, while that of hepatitis C virus (HCV) infection is controversial. This study investigated the epidemiology of HBV and HCV infections and assessed the beneficial effect of the vaccination strategy for hepatitis B in Northeastern China. METHODS: From June 2016 to August 2016, 6541 residents of Changchun in Northeastern China were recruited for this cross-sectional study. Demographic characteristics as well as HBV and HCV serological test results were reviewed and analyzed. RESULTS: Among all study participants, 3.8% and 0.36% tested positive for hepatitis B surface antigen (HBsAg) and anti-HCV, respectively. The HBsAg- and anti-HCV-positive rates were significantly higher in male participants (4.58% and 0.43%) than in female individuals (3.0% and 0.33%). Notably, among all age groups, the lowest rate of HBsAg positivity (0.2%) was found in children born after the implementation of the vaccination strategy for hepatitis B. Conversely, participants aged 40-49 years had significantly greater positive rates of HBsAg (5.9%) compared with those of other age groups. Furthermore, the highest rates of anti-HCV positivity (1.1%) were observed in participants aged 50-59 years. CONCLUSIONS: The rate of HBsAg-positivity declined significantly following successful implementation of the policy on hepatitis B vaccination, indicating a beneficial impact on the control of HBV infection. However, only a slight decrease was observed in the anti-HCV-positivity rate, identifying an area in need of improvement within viral hepatitis prevention and control programs in China.

Factors influencing the occupational injuries of physical therapists in Taiwan: A hierarchical linear model approach.

BACKGROUND: The evidence literature suggests that physical therapy practitioners are subjected to a high probability of acquiring work-related injuries, but only a few studies have specifically investigated Taiwanese physical therapy practitioners. OBJECTIVE: This study was conducted to determine the relationships among individual and group hospital-level factors that contribute to the medical expenses for the occupational injuries of physical therapy practitioners in Taiwan. PARTICIPANTS: Physical therapy practitioners in Taiwan with occupational injuries were selected from the 2013 National Health Insurance Research Databases (NHIRD). METHODS: The age, gender, job title, hospitals attributes, and outpatient data of physical therapy practitioners who sustained an occupational injury in 2013 were obtained with SAS 9.3. SPSS 20.0 and HLM 7.01 were used to conduct descriptive and hierarchical linear model analyses, respectively. RESULTS: The job title of physical therapy practitioners at the individual level and the hospital type at the group level exert positive effects on per person medical expenses. Hospital hierarchy moderates the individual-level relationships of age and job title with the per person medical expenses. CONCLUSION: Considering that age, job title, and hospital hierarchy affect medical expenses for the occupational injuries of physical therapy practitioners, we suggest strengthening related safety education and training and elevating the self-awareness of the risk of occupational injuries of physical therapy practitioners to reduce and prevent the occurrence of such injuries.

Optimal cut-off of obesity indices to predict cardiovascular disease risk factors and metabolic syndrome among adults in Northeast China.

BACKGROUND: CVD risk factors (hypertension, dyslipidemia and diabetes) and MetS are closely related to obesity. The selection of an optimal cut-off for various obesity indices is particularly important to predict CVD risk factors and MetS. METHODS: Sixteen thousand seven hundred sixty-six participants aged 18-79 were recruited in Jilin Province in 2012. Five obesity indices, including BMI, WC, WHR, WHtR and BAI were investigated. ROC analyses were used to evaluate the predictive ability and determine the optimal cut-off values of the obesity indices for CVD risk factors and MetS. RESULTS: BMI had the highest adjusted ORs, and the adjusted ORs for hypertension, dyslipidemia, diabetes and MetS were 1.19 (95 % CI, 1.17 to 1.20), 1.20 (95 % CI, 1.19 to 1.22), 1.12 (95 % CI, 1.10 to 1.13), and 1.40 (95 % CI, 1.38 to 1.41), respectively. However, BMI did not always have the largest adjusted AUROC. In general, the young age group (18 ~ 44) had higher ORs and AUROCs for CVD risk factors and MetS than those of the other age groups. In addition, the optimal cut-off values for WC and WHR in males were relatively higher than those in females, whereas the BAI in males was comparatively lower than that in females. CONCLUSIONS: The appropriate obesity index, with the corresponding optimal cut-off values, should be selected in different research studies and populations. Generally, the obesity indices and their optimal cut-off values are: BMI (24 kg/m2), WC (male: 85 cm; female: 80 cm), WHR (male: 0.88; female: 0.85), WHtR (0.50), and BAI (male: 25 cm; female: 30 cm). Moreover, WC is superior to other obesity indices in predicting CVD risk factors and MetS in males, whereas, WHtR is superior to other obesity indices in predicting CVD risk factors and MetS in females.

Comparison of the Combined Obesity Indices to Predict Cardiovascular Diseases Risk Factors and Metabolic Syndrome in Northeast China.

BACKGROUND: Obesity is associated with cardiovascular disease (CVD) risk factors (hypertension, dyslipidemia and diabetes) and metabolic syndrome (MetS), and it may be flawed that most studies only use one obesity index to predict these risk factors. Therefore, our study aims to compare the various combined obesity indices systematically, and to find the optimal combined obesity indices to predict CVD risk factors and MetS. METHODS: A total of 16,766 participants aged 18-79 years old were recruited in Jilin Province in 2012. Receiver operating characteristic curve (ROC) curves and multiple logistic regressions were used to evaluate the predictive capacity of the combined obesity indices for CVD risk factors and MetS. RESULTS: The adjusted area under receiver operating characteristic (AUROC) with two combined obesity indices had been improved up to 19.45%, compared with one single obesity index. In addition, body mass index (BMI) and waist circumference (WC) were the optimal combinations, where the AUROC (95% confidence interval (CI)) for hypertension, dyslipidemia, diabetes and MetS in males were 0.730 (0.718, 0.740), 0.694 (0.682, 0.706), 0.725 (0.709, 0.742) and 0.820 (0.810, 0.830), and in females were 0.790 (0.780, 0.799), 0.727 (0.717, 0.738), 0.746 (0.731, 0.761) and 0.828 (0.820, 0.837), respectively. CONCLUSIONS: The more abnormal obesity indices that one has the higher the risk for CVD risk factors and MetS, especially in males. In addition, the combined obesity indices have better predictions than one obesity index, where BMI and WC are the optimal combinations.

Human flesh search: a supplemental review.

Human flesh search (HFS), a phenomenon that has recently emerged over the Internet, represents the interaction between the virtual and real worlds. The term "HFS" is equivalent to "cyber manhunt" in the West, although there were more large-scale HFS events reported in the East recently. While the majority of academic articles on HFS have focused on the Chinese context, the phenomenon has also been reported in many countries and involves diverse issues such as the controversy between privacy violation and public opinion. Based on 16 HFS references, a review paper by Chen and Sharma summarizes core issues on growth, incidents, distinctive attributes, key benefits and drawbacks, findings, and research gaps and opportunities. Echoing their call for a global HFS context, the current article provides a Taiwanese HFS context based on 32 reported incidents in Taiwan. To conduct an incremental HFS review, this study expands the reference base to 33 carefully selected academic articles from China and Taiwan. The review findings range from 6 derived HFS perspectives supplementing each article, 12 frequently mentioned HFS concepts, and 4 additional research directions. The resulting comprehensive knowledge of HFS, along with that contributed by Chen and Sharma, can be considered a useful reference framework for future HFS studies and policy making.

Linking hypoxic and oxidative insults to cell death mechanisms in models of ALS.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that is characterized by a progressive, selective loss of motor neurons (MN) in brain and spinal cord. The mechanisms of selective and age-dependent MN degeneration in ALS have not been defined. Recent studies suggest that the elevation of intracellular oxidative toxicity contributes to death of MN, but the molecular pathways remain largely unknown. In order to study the possible molecular pathways that the oxidative toxicity induced MN death in ALS, a MN-like cell NSC34, a primary neuronal cell (PNC) of mouse prontal cortex, and a G93A-SOD1 transgenic mouse model were used. Exposure of NSC34 and PNC to cobalt chloride or chronic sustained hypoxic conditions showed a dramatic increase of cellular Hif-1α (hypoxia inducing factor-1α), HO-1 (heme oxygenases-1), and UCP4 (uncoupling protein 4) expression by Western blot analysis, accompanied with increasing cellular apoptosis by histone protein release assay. In an ALS mouse model, the caspase 3 activation, Aif (apoptosis inducing factor), cytochrome c redistribution in MN of spinal cord significantly increased at 70days of disease progression, and Hif-1α expression significantly increased at whole disease stages by an immunohistochemical positive cell counting and Western blot analysis, respectively. The data on this in vitro and in vivo study suggested that oxidative toxicity promoted multiple molecular pathways associated with MN death in ALS and at least were partially associated with the changes of Hif-1α, HO-1, UCP4 expressive increment, caspase 3 activation and Aif, cytochrome c redistribution.

Description of distributed features of the nestin-containing cells in brains of adult mice: a potential source of neural precursor cells.

The distribution of neural precursor cells (NPCs) in adult mice brain has so far not been described. Therefore, we investigated the distribution of NPCs by analyzing the nestin-containing cells (NCCs) in distinct brain regions of adult nestin second-intron enhancer-controlled LacZ reporter transgenic mice through LacZ staining. Results showed that NCCs existed in various regions of adult mouse brain. In cerebellum, the greatest number of NCCs existed in cortex of the simple lobule, followed by cortex of the cerebellar lobule. In olfactory bulb, NCCs were most numerous in the granular cell layer, followed by the mitral cell layer and the internal plexiform, glomerular, and external plexiform layers. In brain nuclei (nu), NCCs were most numerous in the marginal nu, followed by the brainstem and diencephalon nu. NCCs in sensory nu of brainstem were more numerous than in motor nu, and NCCs in the dorsal of sensory nu were more numerous than in the ventral part. In brain ventricle systems, NCCs were largely distributed in the center of and external to the lateral ventricle, the inferior part of the third ventricle, the dorsal and inferior parts of the fourth ventricle, and the gray matter around the cerebral aqueduct. NCCs in the left vs. right brain were not significantly different. These data collectively indicate that NCCs were extensively distributed in the cerebellum and olfactory bulb, the partial nu of the marginal system, the partial brain nu adjacent to brain ventricle systems, the subependymal zone, and the cerebral cortex around the marginal lobe and were a potential source of NPCs.

Nestin-positive cells in the spinal cord: a potential source of neural stem cells.

Some literatures have reported neural precursor cells (NPCs) exist in spinal cord of adult mammal, however, the NPCs distribution feature in spinal cord of adult mice so far is not described in detail. In order to observe and compare the distribution feature of NPCs in various spinal cord regions of adult mice, to research a potential source of neural stem cells (NSCs), we obtained NPCs distribution feature by analyzing the distribution of the nestin-containing cells (NCCs) in spinal cord of adult nestin second-intron enhancer controlled LacZ reporter transgenic mice (pNes-Tg) with LacZ staining and positive cell quantification. The results showed that: NCCs were observed in various regions of spinal cord of adult mice, but amount of NCCs was different in distinct region, the rank order of NCCs amount in various spinal cord regions was dorsal horn region greater than central canal greater than the ventral and lateral horn. NCCs in dorsal horn region mainly distributed in substantia gelatinosa, NCCs in central canal mainly distributed in ependymal zone, on the contrary, NCCs in ventral, lateral horn, medullae, nucleus regions of spinal cord were comparatively less. The rank order of NCCs amount in various spinal cord segments was cervical segment greater than lumbar sacral segment greater than thoracic segment. There was no significantly difference between NCCs amount in the left and right sides, and within cervical 1-7, thoracic 1-12, lumbar 1-5, sacral segment of spinal cord in adult mice. These data collectively indicate that NPCs extensively distribute in various regions of spinal cord of adult mice, especially in substantia gelatinosa and ependymal zone. NPCs in cervical segment are abundant, NPCs in thoracic segment are the least while compared the different spinal cord segment, the NPCs in various regions of spinal cord of adult mice are a potential source of NSCs.

Domoic acid induced spinal cord lesions in adult mice: evidence for the possible molecular pathways of excitatory amino acids in spinal cord lesions.

Domoic acid (DA) is an excitatory amino acids (EAAs) analog which induced excitotoxicity lesion to central nervous system, but whether induced adult animal spinal cord is not known, furthermore, previous studies have shown that EAAs play an important role in spinal cord lesion, however, the molecular pathways in spinal cord lesion are not fully known. Therefore, a motor neuron-like cell culture system and a DA-induced spinal cord lesioned mice model were used to study the effect of DA on spinal cord in adult mice and the possible molecular pathways of EAAs in spinal cord lesions. Exposure of motor neuron-like cells NSC34 to DA dramatically increased reactive oxygen species (ROS) production by the DCF fluorescent oxidation assay, reduced mitochondrial function by MTT assay, cell viability by trypan blue exclusion assay, and was accompanied by an increase of cell apoptosis by histone protein release assay. In DA-induced spinal cord lesioned mice model, we showed that the decrease of proteasome activity, increase of UCP4 expression by immunohistochemistry and neural cell apoptosis by TUNEL staining, and was accompanied by an decrease of motor disturbance grade during the different stages of DA treatment. Taken together, the in vitro and in vivo data presented in the current report demonstrated that DA induces spinal cord lesions in adult mice, and the multiple molecular pathways promoted by EAAs in spinal cord lesions, at least partially was associated with ROS generation increase, mitochondrial dysfunction, proteasome activity decrease and UCP4 expression increase.