Proteomic profiling of ovarian clear cell carcinomas identifies prognostic biomarkers for chemotherapy.

Clear cell ovarian carcinoma (CCOC) is a relatively rare subtype of ovarian cancer (OC) with high degree of resistance to standard chemotherapy. Little is known about the underlying molecular mechanisms, and it remains a challenge to predict its prognosis after chemotherapy. Here, we first analyzed the proteome of 35 formalin-fixed paraffin-embedded (FFPE) CCOC tissue specimens from a cohort of 32 patients with CCOC (H1 cohort) and characterized 8697 proteins using data-independent acquisition mass spectrometry (DIA-MS). We then performed proteomic analysis of 28 fresh frozen (FF) CCOC tissue specimens from an independent cohort of 24 patients with CCOC (H2 cohort), leading to the identification of 9409 proteins with DIA-MS. After bioinformatics analysis, we narrowed our focus to 15 proteins significantly correlated with the recurrence free survival (RFS) in both cohorts. These proteins are mainly involved in DNA damage response, extracellular matrix (ECM), and mitochondrial metabolism. Parallel reaction monitoring (PRM)-MS was adopted to validate the prognostic potential of the 15 proteins in the H1 cohort and an independent confirmation cohort (H3 cohort). Interferon-inducible transmembrane protein 1 (IFITM1) was observed as a robust prognostic marker for CCOC in both PRM data and immunohistochemistry (IHC) data. Taken together, this study presents a CCOC proteomic data resource and a single promising protein, IFITM1, which could potentially predict the recurrence and survival of CCOC.

Microstructural abnormalities of white matter in the cingulum bundle of adolescents with major depression and non-suicidal self-injury.

BACKGROUND: Non-suicidal self-injury (NSSI) is prevalent in major depressive disorder (MDD) during adolescence, but the underlying neural mechanisms are unclear. This study aimed to investigate microstructural abnormalities in the cingulum bundle associated with NSSI and its clinical characteristics. METHODS: 130 individuals completed the study, including 35 healthy controls, 47 MDD patients with NSSI, and 48 MDD patients without NSSI. We used tract-based spatial statistics (TBSS) with a region of interest (ROI) analysis to compare the fractional anisotropy (FA) of the cingulum bundle across the three groups. receiver-operating characteristics (ROC) analysis was employed to evaluate the ability of the difficulties with emotion regulation (DERS) score and mean FA of the cingulum to differentiate between the groups. RESULTS: MDD patients with NSSI showed reduced cingulum integrity in the left dorsal cingulum compared to MDD patients without NSSI and healthy controls. The severity of NSSI was negatively associated with cingulum integrity (r = -0.344, p = 0.005). Combining cingulum integrity and DERS scores allowed for successful differentiation between MDD patients with and without NSSI, achieving a sensitivity of 70% and specificity of 83%. CONCLUSIONS: Our study highlights the role of the cingulum bundle in the development of NSSI in adolescents with MDD. The findings support a frontolimbic theory of emotion regulation and suggest that cingulum integrity and DERS scores may serve as potential early diagnostic tools for identifying MDD patients with NSSI.

Synthesis and Evaluation of [18F]AlF-NOTA-c-DVAP: A Novel PET Probe for Imaging GRP78 in Cancer.

GRP78, a member of the HSP70 superfamily, is an endoplasmic reticulum chaperone protein overexpressed in various cancers, making it a promising target for cancer imaging and therapy. Positron emission tomography (PET) imaging offers unique advantages in real time, noninvasive tumor imaging, rendering it a suitable tool for targeting GRP78 in tumor imaging to guide targeted therapy. Several studies have reported successful tumor imaging using PET probes targeting GRP78. However, existing PET probes face challenges such as low tumor uptake, inadequate in vivo distribution, and high abdominal background signal. Therefore, this study introduces a novel peptide PET probe, [18F]AlF-NOTA-c-DVAP, for targeted tumor imaging of GRP78. [18F]AlF-NOTA-c-DVAP was radiolabeled with fluoride-18 using the aluminum-[18F]fluoride ([18F]AlF) method. The study assessed the partition coefficients, stability in vitro, and metabolic stability of [18F]AlF-NOTA-c-DVAP. Micro-PET imaging, pharmacokinetic analysis, and biodistribution studies were carried out in tumor-bearing mice to evaluate the probe's performance. Docking studies and pharmacokinetic analyses of [18F]AlF-NOTA-c-DVAP were also performed. Immunohistochemical and immunofluorescence analyses were conducted to confirm GRP78 expression in tumor tissues. The probe's binding affinity to GRP78 was analyzed by molecular docking simulation. [18F]AlF-NOTA-c-DVAP was radiolabeled in just 25 min with a high yield of 51 ± 16%, a radiochemical purity of 99%, and molar activity within the range of 20-50 GBq/µmol. [18F]AlF-NOTA-c-DVAP demonstrated high stability in vitro and in vivo, with a logD value of -3.41 ± 0.03. Dynamic PET imaging of [18F]AlF-NOTA-c-DVAP in tumors showed rapid uptake and sustained retention, with minimal background uptake. Biodistribution studies revealed rapid blood clearance and excretion through the kidneys following a single-compartment reversible metabolic model. In PET imaging, the T/M ratios for A549 tumors (high GRP78 expression), MDA-MB-231 tumors (medium expression), and HepG2 tumors (low expression) at 60 min postintravenous injection were 10.48 ± 1.39, 6.25 ± 0.47, and 3.15 ± 1.15% ID/g, respectively, indicating a positive correlation with GRP78 expression. This study demonstrates the feasibility of using [18F]AlF-NOTA-c-DVAP as a PET tracer for imaging GRP78 in tumors. The probe shows promising results in terms of stability, specificity, and tumor targeting. Further research may explore the clinical utility and potential therapeutic applications of this PET tracer for cancer diagnosis.

Distinguishing bipolar depression, bipolar mania, and major depressive disorder by gut microbial characteristics.

BACKGROUND: Gut microbial disturbance has been widely confirmed in mood disorders. However, little is known about whether gut microbial characteristics can distinguish major depressive disorder (MDD), bipolar depression (BP-D), and bipolar mania (BP-M). METHODS: This was a prospective case-control study. The composition of gut microbiota was profiled using 16S ribosomal RNA (rRNA) gene sequencing of fecal samples and compared between healthy controls (HC; n = 46), MDD (n = 51), BP-D (n = 44), and patients with BP-M (n = 45). RESULTS: Gut microbial compositions were remarkably changed in the patients with MDD, BP-D, and BP-M. Compared to HC, distinct gut microbiome signatures were found in MDD, BP-D, and BP-M, and some gut microbial changes were overlapping between the three mood disorders. Furthermore, we identified a signature of 7 operational taxonomic units (OUT; Prevotellaceae-related OUT22, Prevotellaceae-related OUT31, Prevotellaceae-related OTU770, Ruminococcaceae-related OUT70, Bacteroidaceae-related OTU1536, Propionibacteriaceae-related OTU97, Acidaminococcaceae-related OTU34) that can distinguish patients with MDD from those with BP-D, BP-M, or HC, with area under the curve (AUC) values ranging from 0.910 to 0.996. CONCLUSION: Our results provide the clinical rationale for the discriminative diagnosis of MDD, BP-D, and BP-M by characteristic gut microbial features.

Diagnosis of dysthyroid optic neuropathy: combined value of orbital MRI and intracranial visual pathway diffusion kurtosis imaging.

OBJECTIVES: To evaluate the combined performance of orbital MRI and intracranial visual pathway diffusion kurtosis imaging (DKI) in diagnosing dysthyroid optic neuropathy (DON). METHODS: We retrospectively enrolled 61 thyroid-associated ophthalmopathy (TAO) patients, including 25 with DON (40 eyes) and 36 without DON (72 eyes). Orbital MRI-based apical muscle index (MI), diameter index (DI) of the optic nerve (ON), area index (AI) of the ON, apparent diffusion coefficient (ADC) and signal intensity ratio (SIR) of the ON, DKI-based kurtosis fractional anisotropy (KFA) and mean kurtosis (MK) of the optic tract (OT), optic radiation (OR), and Brodmann areas (BAs) 17, 18, and 19 were measured and compared between groups. The diagnostic performances of models were evaluated using receiver operating characteristic curve analyses and compared using the DeLong test. RESULTS: TAO patients with DON had significantly higher apical MI, apical AI, and SIR of the ON, but significantly lower ADC of the ON than those without DON (p < 0.05). Meanwhile, the DON group exhibited significantly lower KFA across the OT, OR, BA17, BA18, and BA19 and lower MK at the OT and OR than the non-DON group (p < 0.05). The model integrating orbital MRI and intracranial visual pathway DKI parameters performed the best in diagnosing DON (AUC = 0.926), with optimal diagnostic sensitivity (80%) and specificity (94.4%), followed by orbital MRI combination (AUC = 0.890), and then intracranial visual pathway DKI combination (AUC = 0.832). CONCLUSION: Orbital MRI and intracranial visual pathway DKI can both assist in diagnosing DON. Combining orbital and intracranial imaging parameters could further optimize diagnostic efficiency. CLINICAL RELEVANCE STATEMENT: The novel finding could bring novel insights into the precise diagnosis and treatment of dysthyroid optic neuropathy, accordingly, contributing to the improvement of the patients' prognosis and quality of life in the future. KEY POINTS: • Orbital MRI and intracranial visual pathway diffusion kurtosis imaging can both assist in diagnosing dysthyroid optic neuropathy. • Combining orbital MRI and intracranial visual pathway diffusion kurtosis imaging optimized the diagnostic efficiency of dysthyroid optic neuropathy.

Prediction of Early Antidepressant Efficacy in Patients with Major Depressive Disorder Based on Multidimensional Features of rs-fMRI and P11 Gene DNA Methylation: Prédiction de l'efficacité précoce d'un antidépresseur chez des patients souffrant du trouble dépressif majeur d'après les caractéristiques multidimensionnelles de la méthylation de l'ADN du gène P11 et de la IRMf-rs.

OBJECTIVE: This study established a machine learning model based on the multidimensional data of resting-state functional activity of the brain and P11 gene DNA methylation to predict the early efficacy of antidepressant treatment in patients with major depressive disorder (MDD). METHODS: A total of 98 Han Chinese MDD were analysed in this study. Patients were divided into 51 responders and 47 nonresponders according to whether the Hamilton Depression Rating Scale-17 items (HAMD-17) reduction rate was ≥50% after 2 weeks of antidepressant treatment. At baseline, the Illumina HiSeq Platform was used to detect the methylation of 74 CpG sites of the P11 gene in peripheral blood samples. Resting-state functional magnetic resonance imaging (rs-fMRI) scan detected the amplitude of low-frequency fluctuations (ALFF), regional homogeneity (ReHo), and functional connectivity (FC) in 116 brain regions. The least absolute shrinkage and selection operator analysis method was used to perform feature reduction and feature selection. Four typical machine learning methods were used to establish support vector machine (SVM), random forest (RF), Naïve Bayes (NB), and logistic regression (LR) prediction models based on different combinations of functional activity of the brain, P11 gene DNA methylation and clinical/demographic features after screening. RESULTS: The SVM model based on ALFF, ReHo, FC, P11 methylation, and clinical/demographic features showed the best performance, with 95.92% predictive accuracy and 0.9967 area under the receiver operating characteristic curve, which was better than RF, NB, and LR models. CONCLUSION: The multidimensional data features combining rs-fMRI, DNA methylation, and clinical/demographic features can predict the early antidepressant efficacy in MDD.

Functional characterization of a rare pathogenic variant c.875G > A, p.(Cys292Tyr) in COMP.

BACKGROUND: The protein encoded by the cartilage oligomeric matrix protein (COMP) gene is a noncollagenous extracellular matrix (ECM) protein that is important for chondrocyte formation and growth. Variations in the COMP gene cause pseudoachondroplasia (PSACH), which is mainly characterized by short-limbed dwarfing in the clinic. AIMS: To characterize the function of a rare pathogenic variant in the COMP gene (c.875G > A, p.Cys292Tyr). MATERIALS & METHODS: We performed 3D structural analysis, in vitro expression analysis, and immunofluorescence to characterize the effects of the variant on protein structure, expression, and cellular localization respectively. RESULTS: Variation modeling showed that the interactions between amino acids were changed after the variation, and there were 31 changes in the secondary structure of mutant COMP (MT-COMP). Western blot showed that the intracellular quantity of MT-COMP was higher than the wild-type COMP (WT-COMP). Cellular immunofluorescence results showed that WT-COMP was less abundant and homogenously distributed in cells, while the MT-COMP accumulated in the cytoplasm. DISCUSSION: Herein, we report a variant of COMP in a Chinese family with PSACH. We have shown that the rare missense variant, COMP c.875G > A, previously reported in ClinVar and identified in our patient, results in excessive accumulation of mutant protein in the cytoplasm, and is therefore pathogenic. CONCLUSION: Through in silico and experimental analyses, we provide evidence that COMP c.875G > A is the likely cause of PSACH in a Chinese family.

Altered dynamic brain activity and functional connectivity in thyroid-associated ophthalmopathy.

Although previous neuroimaging evidence has confirmed the brain functional disturbances in thyroid-associated ophthalmopathy (TAO), the dynamic characteristics of brain activity and functional connectivity (FC) in TAO were rarely concerned. The present study aims to investigate the alterations of temporal variability of brain activity and FC in TAO using resting-state functional magnetic resonance imaging (rs-fMRI). Forty-seven TAO patients and 30 age-, gender-, education-, and handedness-matched healthy controls (HCs) were enrolled and underwent rs-fMRI scanning. The dynamic amplitude of low-frequency fluctuation (dALFF) was first calculated using a sliding window approach to characterize the temporal variability of brain activity. Based on the dALFF results, seed-based dynamic functional connectivity (dFC) analysis was performed to identify the temporal variability of efficient communication between brain regions in TAO. Additionally, correlations between dALFF and dFC and the clinical indicators were analyzed. Compared with HCs, TAO patients displayed decreased dALFF in the left superior occipital gyrus (SOG) and cuneus (CUN), while showing increased dALFF in the left triangular part of inferior frontal gyrus (IFGtriang), insula (INS), orbital part of inferior frontal gyrus (ORBinf), superior temporal gyrus (STG) and temporal pole of superior temporal gyrus (TPOsup). Furthermore, TAO patients exhibited decreased dFC between the left STG and the right middle occipital gyrus (MOG), as well as decreased dFC between the left TPOsup and the right calcarine fissure and surrounding cortex (CAL) and MOG. Correlation analyses showed that the altered dALFF in the left SOG/CUN was positively related to visual acuity (r = .409, p = .004), as well as the score of QoL for visual functioning (r = .375, p = .009). TAO patients developed abnormal temporal variability of brain activity in areas related to vision, emotion, and cognition, as well as reduced temporal variability of FC associated with vision deficits. These findings provided additional insights into the neurobiological mechanisms of TAO.

Altered neurovascular coupling in thyroid-associated ophthalmopathy: A combined resting-state fMRI and arterial spin labeling study.

Besides the well-documented ophthalmic manifestations, thyroid-associated ophthalmopathy (TAO) is believed to be related to emotional and psychological abnormalities. Given the previous neuroimaging evidence, we hypothesized that TAO patients would have altered neurovascular coupling associated with clinical-psychiatric disturbances. This study was to investigate neurovascular coupling changes in TAO by combining resting-state functional magnetic resonance imaging (rs-fMRI) and arterial spin labeling (ASL) techniques. Amplitude of low-frequency fluctuation (ALFF) was calculated from rs-fMRI, and cerebral blood flow (CBF) was computed from ASL in 37 TAO patients and 21 healthy controls (HCs). Global neurovascular coupling was assessed by across-voxel CBF-ALFF correlation, and regional neurovascular coupling was evaluated by CBF/ALFF ratio. Auxiliary analyses were performed using fractional ALFF (fALFF) and regional homogeneity (ReHo) as rs-fMRI measures. Compared with HCs, TAO patients showed significantly reduced global CBF-ALFF coupling. Moreover, TAO patients exhibited decreased CBF/ALFF ratio in the left lingual gyrus (LG)/fusiform gyrus (FFG), and increased CBF/ALFF ratio in the bilateral precuneus (PCu). In TAOs, CBF/ALFF ratio in the left LG/FFG was positively correlated with visual acuity, while CBF/ALFF ratio in the bilateral PCu was negatively correlated with Montreal Cognitive Assessment score. The auxiliary analyses showed trends of reduced global neurovascular coupling (i.e., CBF-fALFF correlation and CBF-ReHo correlation), as well as significant altered regional neurovascular coupling (i.e., CBF/fALFF ratio and CBF/ReHo ratio) in several brain regions. These findings indicated that TAO patients had altered neurovascular coupling in the visual and higher-order cognitive cortices. The neurovascular decoupling might be a possible neuropathological mechanism of TAO.

Predicting the diagnosis of various mental disorders in a mixed cohort using blood-based multi-protein model: a machine learning approach.

The lack of objective diagnostic methods for mental disorders challenges the reliability of diagnosis. The study aimed to develop an easily accessible and useable objective method for diagnosing major depressive disorder (MDD), schizophrenia (SZ), bipolar disorder (BPD), and panic disorder (PD) using serum multi-protein. Serum levels of brain-derived neurotrophic factor (BDNF), VGF (non-acronymic), bicaudal C homolog 1 (BICC1), C-reactive protein (CRP), and cortisol, which are generally recognized to be involved in different pathogenesis of various mental disorders, were measured in patients with MDD (n = 50), SZ (n = 50), BPD (n = 55), and PD along with 50 healthy controls (HC). Linear discriminant analysis (LDA) was employed to construct a multi-classification model to classify these mental disorders. Both leave-one-out cross-validation (LOOCV) and fivefold cross-validation were applied to validate the accuracy and stability of the LDA model. All five serum proteins were included in the LDA model, and it was found to display a high overall accuracy of 96.9% when classifying MDD, SZ, BPD, PD, and HC groups. Multi-classification accuracy of the LDA model for LOOCV and fivefold cross-validation (within-study replication) reached 96.9 and 96.5%, respectively, demonstrating the feasibility of the blood-based multi-protein LDA model for classifying common mental disorders in a mixed cohort. The results suggest that combining multiple proteins associated with different pathogeneses of mental disorders using LDA may be a novel and relatively objective method for classifying mental disorders. Clinicians should consider combining multiple serum proteins to diagnose mental disorders objectively.

Comparative Evaluation of Proteome Discoverer and FragPipe for the TMT-Based Proteome Quantification.

Isobaric labeling-based proteomics is widely applied in deep proteome quantification. Among the platforms for isobaric labeled proteomic data analysis, the commercial software Proteome Discoverer (PD) is widely used, incorporating the search engine CHIMERYS, while FragPipe (FP) is relatively new, free for noncommercial purposes, and integrates the engine MSFragger. Here, we compared PD and FP over three public proteomic data sets labeled using 6plex, 10plex, and 16plex tandem mass tags. Our results showed the protein abundances generated by the two software are highly correlated. PD quantified more proteins (10.02%, 15.44%, 8.19%) than FP with comparable NA ratios (0.00% vs. 0.00%, 0.85% vs. 0.38%, and 11.74% vs. 10.52%) in the three data sets. Using the 16plex data set, PD and FP outputs showed high consistency in quantifying technical replicates, batch effects, and functional enrichment in differentially expressed proteins. However, FP saved 93.93%, 96.65%, and 96.41% of processing time compared to PD for analyzing the three data sets, respectively. In conclusion, while PD is a well-maintained commercial software integrating various additional functions and can quantify more proteins, FP is freely available and achieves similar output with a shorter computational time. Our results will guide users in choosing the most suitable quantification software for their needs.

High-quality, large-scale, semi-thin, & ultra-thin sections of the optic nerve in large animals: An optimized procedure.

Large animal model of optic nerve (ON) injury is an essential tool for translational medicine. Perfusion fixation with paraformaldehyde is mainly used for preparing the semi-thin (1-2 µm thick) and ultra-thin (<0.5 µm thick) sections of the ON tissues. However, this conventional fixation technique in large animals needs a large volume of fixatives, which increases the risk of toxic exposure and is environmentally unfriendly. Additionally, fixed residual ON cannot be used for other tests that require fresh tissue samples. Although conventional immersion fixation is feasible for preparing a semi-thin section of the ON in small animals (0.2-0.6 mm in diameter), it faces technical challenges when fixing the ON of large animals (3 mm in diameters), as increased diameter limits the permeability of the fixatives into deeper tissue. Therefore, we optimized the immersion-fixation method to obtain high-quality, large-scale, semi-thin, and ultra-thin sections for the ON of goat and rhesus macaques. Using this optimized technique, the ON microstructure was well preserved throughout the entire area of 1.5*1.5 square millimeters, allowing confident quantification of axon density/diameter on semi-thin section and identification of specific organelles and glial cells on ultra-thin sections. Furthermore, the optimized technique is a quick, simple, and environmentally friendly fixation method. Notably, the ON regions of large animals with or without an intact neurovascular system can be prepared for light and electron microscopy. In contrast, the residual unfixed ON from the same animal can be further utilized for experiments such as tissue culture and biomolecular tests.

Navigation-guided nasal endoscopic surgery for acute vision loss caused by fibrous dysplasia: a case report and review of literatures.

BACKGROUND: Bone fibrous dysplasia is a benign disease of bone tissue dysplasia. Vision impairment is the commonest neurological complication of craniofacial fibrous dysplasia. Most of the vision loss caused by craniofacial fibrous dysplasia is usually a gradual process. Very few present with acute visual impairment as described in our case. CASE PRESENTATION: We report a patient with fibrous dysplasia presenting rapidly progressive visual loss in the left eye secondary to bone cyst formation. Transnasal endoscopic surgery guided by navigation with drainage and curettage of this bone cyst and orbital decompression resulted in progressive improvement in visual acuity that returned to normal 1 month post-operatively. CONCLUSIONS: In cases with acute visual loss due to fibrous dysplasia, emergency surgical treatment should be considered to preserve vision. In the surgical approach, navigation-guided nasal endoscopic surgery may be preferred because of its advantages.

Characteristics of post-traumatic embitterment disorder of inpatients in a general hospital in China.

OBJECTIVE: Embitterment and post-traumatic embitterment disorder (PTED) is critical, merging through different cultures. We explored the prevalence and related clinical characteristics of PTED of inpatients in a general hospital in China. METHOD: Two hundred inpatients (aged 18-65 years) from different departments were recruited by convenient sampling and standardized diagnostic interviews of PTED. Demographic data, Post-traumatic Embitterment Disorder Self-Rating Scale (PTED-21), the Patient Health Questionnaire depression scale (PHQ-9), Generalized Anxiety Disorder-7 (GAD-7) and the Patient Health Questionnaire depression scale (PHQ-15) were collected on all participants. RESULTS: The prevalence of PTED was 21% (42/200) in inpatients in China; besides, the rate of increased syndromal embitterment is 28% (56/200), including 42 patients diagnosed with PTED. PTED was mainly associated with stressful events, such as illness, work and complicated interpersonal relationships. Rheumatology department and respiratory department have the highest and second highest prevalence of PTED among all departments. PTED-21 scores were significantly correlated with PHQ-9, GAD-7 and PHQ-15 (all P < 0.01). CONCLUSIONS: The present study shows that embitterment is a critical negative emotion in inpatients with somatic illnesses with comorbid depression, anxiety and somatic symptoms. PTED and feelings of embitterment should be given proper attention in diagnosing somatic patients, and it is crucial to enhance PTED screening and intervention in the future. Future intervention studies on post-traumatic embitterment disorder could be done in general and especially in psychosomatic and somatic medicine.

The study of 9,10-dihydroacridine derivatives as a new and effective molecular scaffold for antibacterial agent development.

The emergence of worldwide spreading drug-resistant bacteria has been a serious threat to public health during the past decades. The development of new and effective antibacterial agents to address this critical issue is an urgent action. In the present study, we investigated the antibacterial activity of two 9,10-dihydroacridine derivatives and their mechanism. Both compounds were found possessing strong antibacterial activity against some selected Gram-positive bacteria including MRSA, VISA and VRE. The biological study suggests that the compounds promoted FtsZ polymerization and also disrupted Z-ring formation at the dividing site and consequently, the bacterial cell division is interrupted and causing cell death.

In vivo evaluation of outer retinal function and structure after retrobulbar optic nerve crush by lateral orbitotomy in goats.

Large animal model of optic nerve crush (ONC) plays an important role in translating novel therapeutic strategies developed in rodent model to clinical application. Due to the poor accessibility of the optic nerve (ON) in humans and large animals, lateral orbitotomy is needed to expose the retrobulbar ON. This study was to explore the effects of ONC and ON exposure with lateral orbitotomy (sham surgery) on the outer retinal function and structure in goats by using standard flash electroretinogram (FERG) and spectral-domain optical coherence tomography (SD-OCT). We found that ONC led to a transient reduction in FERG amplitudes at 1 week post injury (wpi), which recovered gradually over 2 months afterwards. Sham surgery alone also caused a similar pattern of amplitude reduction in FERG, although not as significantly as ONC did. Transient outer retinal thickening following ONC occurred at 4 wpi (when progressive thinning of the ganglion cell complex began), peaked at 8 wpi, then recovered gradually at 12 wpi. In contrast, outer retinal thickness remained unchanged statistically 3 months after sham surgery. Fundus fluorescein angiography showed that neither ONC nor ON exposure with lateral orbitotomy significantly caused any significant delay or absence of central retinal vascular filling. In summary, ONC with lateral orbitotomy affects outer retinal function and structure transiently.

The HealthChain Blockchain for Electronic Health Records: Development Study.

BACKGROUND: Health care professionals are required to maintain accurate health records of patients. Furthermore, these records should be shared across different health care organizations for professionals to have a complete review of medical history and avoid missing important information. Nowadays, health care providers use electronic health records (EHRs) as a key to the implementation of these goals and delivery of quality care. However, there are technical and legal hurdles that prevent the adoption of these systems, such as concerns about performance and privacy issues. OBJECTIVE: This study aimed to build and evaluate an experimental blockchain for EHRs, named HealthChain, which overcomes the disadvantages of traditional EHR systems. METHODS: HealthChain is built based on consortium blockchain technology. Specifically, three organizations, namely hospitals, insurance providers, and governmental agencies, form a consortium that operates under a governance model, which enforces the business logic agreed by all participants. Every peer node hosts an instance of the distributed ledger consisting of EHRs and an instance of chaincode regulating the permissions of participants. Designated orderers establish consensus on the order of EHRs and then disseminate blocks to peers. RESULTS: HealthChain achieves functional and nonfunctional requirements. It can store EHRs in a distributed ledger and share them among different participants. Moreover, it demonstrates superior features, such as privacy preservation, security, and high throughput. These are the main reasons why HealthChain is proposed. CONCLUSIONS: Consortium blockchain technology can help to build new EHR systems and solve the problems that prevent the adoption of traditional systems.

MRI reconstruction using deep Bayesian estimation.

PURPOSE: To develop a deep learning-based Bayesian estimation for MRI reconstruction. METHODS: We modeled the MRI reconstruction problem with Bayes's theorem, following the recently proposed PixelCNN++ method. The image reconstruction from incomplete k-space measurement was obtained by maximizing the posterior possibility. A generative network was utilized as the image prior, which was computationally tractable, and the k-space data fidelity was enforced by using an equality constraint. The stochastic backpropagation was utilized to calculate the descent gradient in the process of maximum a posterior, and a projected subgradient method was used to impose the equality constraint. In contrast to the other deep learning reconstruction methods, the proposed one used the likelihood of prior as the training loss and the objective function in reconstruction to improve the image quality. RESULTS: The proposed method showed an improved performance in preserving image details and reducing aliasing artifacts, compared with GRAPPA, ℓ1 -ESPRiT, model-based deep learning architecture for inverse problems (MODL), and variational network (VN), last two were state-of-the-art deep learning reconstruction methods. The proposed method generally achieved more than 3 dB peak signal-to-noise ratio improvement for compressed sensing and parallel imaging reconstructions compared with the other methods. CONCLUSIONS: The Bayesian estimation significantly improved the reconstruction performance, compared with the conventional ℓ1 -sparsity prior in compressed sensing reconstruction tasks. More importantly, the proposed reconstruction framework can be generalized for most MRI reconstruction scenarios.

Profiles of autophagy-related genes in esophageal adenocarcinoma.

BACKGROUND: Several studies have demonstrated autophagy was involved in the process of esophageal adenocarcinoma (EAC). The aim of this study was to explore autophagy-related genes (ARGs) correlated with overall survival (OS) in EAC patients. METHODS: Expressions of ARGs in EAC and normal samples were downloaded from TCGA database. GO and KEGG enrichment analyses were used to investigate the ARGs bioinformatics functions. Univariate and multivariate cox regressions were performed to identify prognostic ARGs and the independent risk factors. ROC curve was established to evaluate the feasibility to predict the prognosis. Finally, the correlations between ARGs and clinical features were further explored. In addition, significantly different ARGs were verified in EAC specimens and normal esophageal mucosal tissues. RESULTS: Thirty significantly different ARGs were selected from EAC and normal tissues. Functional enrichments showed these ARGs were mainly related apoptosis. Multivariate cox regression analyses demonstrated eight ARGs were significantly associated with OS. Among these eight genes, BECN1 (HR = 0.321, P = 0.046), DAPK1 (HR = 0.636, P = 0.025) and CAPN1 (HR = 0.395, P = 0.004) played protective roles in survival. Gender (HR = 0.225, P = 0.032), stage (HR = 5.841, P = 0.008) and risk score (HR = 1.131, P < 0.001) were independent prognostic risk factors. ROC curves showed better efficacy to predict survival using the risk score. Additionally, we found BECN1, DAPK1, VAMP7 and SIRT1 genes were correlated significantly with survival status, gender, primary tumor and tumor stage (all P < 0.05). The experimental results confirmed the BIRC5 was overexpressed and the ITPR1, PRKN were downregulated in the EAC tissues compared with the normal esophageal mucosal tissues (all P < 0.05). CONCLUSION: Our findings suggested that autophagy was involved in the process of EAC. Several ARGs probably could serve as diagnostic and prognostic biomarkers and may help facilitate therapeutic targets in EAC patients.

In vivo evaluation of retinal ganglion cells and optic nerve's integrity in large animals by multi-modality analysis.

Large animal models of optic nerve injury are essential for translating novel findings into effective therapies due to their similarity to humans in many respects. However, most current tests evaluating the integrity of retinal ganglion cells (RGCs) and optic nerve (ON) are based on rodent animal models. We aimed to evaluate and optimize the in vivo methods to assess RGCs and ON's function and structure in large animals in terms of reproducibility, simplicity and sensitivity. Both goats and rhesus macaques were employed in this study. By using goats, we found anesthesia with isoflurane or xylazine resulted in different effects on reproducibility of flash visual evoked potential (FVEP) and pattern electroretinogram (PERG). FVEP with the large-Ganzfeld stimulator was significantly more stable than that with mini-Ganzfeld stimulator. PERG with simultaneous binocular stimulation, with superior simplicity over separate monocular stimulation, was appliable in goats due to undetectable interocular crosstalk of PERG signals. After ON crush in goats, some FVEP components, PERG, OCT and PLR demonstrated significant changes, in line with the histological study. By using rhesus macaque, we found the implicit time of PVEP, FVEP and PERG were significantly more reproducible than amplitudes, and OCT and PLR demonstrated small intersession variation. In summary, we established an optimized system to evaluate integrity of RGCs and ON in large animals in vivo, facilitating usage of large animal models of optic nerve diseases.