Unmasking social attention: The key distinction between social and non-social attention emerges in disengagement, not engagement.

The debate surrounding whether social and non-social attention share the same mechanism has been contentious. While prior studies predominantly focused on engagement, we examined the potential disparity between social and non-social attention from both perspectives of engagement and disengagement, respectively. We developed a two-stage attention-shifting paradigm to capture both attention engagement and disengagement. Combining results from five eye-tracking experiments, we supported that the disengagement of social attention markedly outpaces that of non-social attention, while no significant discrepancy emerges in engagement. We uncovered that the faster disengagement of social attention came from its social nature by eliminating alternative explanations including broader fixation distribution width, reduced directional salience in the peripheral visual field, decreased cue-object categorical consistency, reduced perceived validity, and faster processing time. Our study supported that the distinction between social and non-social attention is rooted in attention disengagement, not engagement.

Orchestrated codelivery of peptide antigen and adjuvant to antigen-presenting cells by using an engineered chimeric peptide enhances antitumor T-cell immunity.

The intrinsic pharmacokinetic limitations of traditional peptide-based cancer vaccines hamper effective cross-presentation and codelivery of antigens and adjuvants, which are crucial for inducing robust antitumor CD8+ T-cell responses. Here, we report the development of a versatile strategy that simultaneously addresses the different pharmacokinetic challenges of soluble subunit vaccines composed of antigens and CpG to modulate vaccine efficacy via translating an engineered chimeric peptide, eTAT, as an intramolecular adjuvant. Linking antigens to eTAT enhanced cytosolic delivery of the antigens. This, in turn, led to improved activation and lymph node-trafficking of antigen-presenting cells and antigen cross-presentation, thus promoting antigen-specific T-cell immune responses. Simple mixing of eTAT-linked antigens and CpG significantly enhanced codelivery of antigens and CpG to the antigen-presenting cells, and this substantially augmented the adjuvant effect of CpG, maximized vaccine immunogenicity and elicited robust and durable CD8+ T-cell responses. Vaccination with this formulation altered the tumor microenvironment and exhibited potent antitumor effects, with generally further enhanced therapeutic efficacy when used in combination with anti-PD1. Altogether, the engineered chimeric peptide-based orchestrated codelivery of antigen and adjuvant may serve as a promising but simple strategy to improve the efficacy of peptide-based cancer vaccines.

Pharmaceutical targeting of OTUB2 sensitizes tumors to cytotoxic T cells via degradation of PD-L1.

PD-1 is a co-inhibitory receptor expressed by CD8+ T cells which limits their cytotoxicity. PD-L1 expression on cancer cells contributes to immune evasion by cancers, thus, understanding the mechanisms that regulate PD-L1 protein levels in cancers is important. Here we identify tumor-cell-expressed otubain-2 (OTUB2) as a negative regulator of antitumor immunity, acting through the PD-1/PD-L1 axis in various human cancers. Mechanistically, OTUB2 directly interacts with PD-L1 to disrupt the ubiquitination and degradation of PD-L1 in the endoplasmic reticulum. Genetic deletion of OTUB2 markedly decreases the expression of PD-L1 proteins on the tumor cell surface, resulting in increased tumor cell sensitivity to CD8+ T-cell-mediated cytotoxicity. To underscore relevance in human patients, we observe a significant correlation between OTUB2 expression and PD-L1 abundance in human non-small cell lung cancer. An inhibitor of OTUB2, interfering with its deubiquitinase activity without disrupting the OTUB2-PD-L1 interaction, successfully reduces PD-L1 expression in tumor cells and suppressed tumor growth. Together, these results reveal the roles of OTUB2 in PD-L1 regulation and tumor evasion and lays down the proof of principle for OTUB2 targeting as therapeutic strategy for cancer treatment.

The potential of swine pseudorabies virus attenuated vaccine for oncolytic therapy against malignant tumors.

BACKGROUND: Oncolytic viruses are now well recognized as potential immunotherapeutic agents against cancer. However, the first FDA-approved oncolytic herpes simplex virus 1 (HSV-1), T-VEC, showed limited benefits in some patients in clinical trials. Thus, the identification of novel oncolytic viruses that can strengthen oncolytic virus therapy is warranted. Here, we identified a live-attenuated swine pseudorabies virus (PRV-LAV) as a promising oncolytic agent with broad-spectrum antitumor activity in vitro and in vivo. METHODS: PRV cytotoxicity against tumor cells and normal cells was tested in vitro using a CCK8 cell viability assay. A cell kinase inhibitor library was used to screen for key targets that affect the proliferation of PRV-LAV. The potential therapeutic efficacy of PRV-LAV was tested against syngeneic tumors in immunocompetent mice, and against subcutaneous xenografts of human cancer cell lines in nude mice. Cytometry by time of flight (CyTOF) and flow cytometry were used to uncover the immunological mechanism of PRV-LAV treatment in regulating the tumor immune microenvironment. RESULTS: Through various tumor-specific analyses, we show that PRV-LAV infects cancer cells via the NRP1/EGFR signaling pathway, which is commonly overexpressed in cancer. Further, we show that PRV-LAV kills cancer cells by inducing endoplasmic reticulum (ER) stress. Moreover, PRV-LAV is responsible for reprogramming the tumor microenvironment from immunologically naïve ("cold") to inflamed ("hot"), thereby increasing immune cell infiltration and restoring CD8+ T cell function against cancer. When delivered in combination with immune checkpoint inhibitors (ICIs), the anti-tumor response is augmented, suggestive of synergistic activity. CONCLUSIONS: PRV-LAV can infect cancer cells via NRP1/EGFR signaling and induce cancer cells apoptosis via ER stress. PRV-LAV treatment also restores CD8+ T cell function against cancer. The combination of PRV-LAV and immune checkpoint inhibitors has a significant synergistic effect. Overall, these findings point to PRV-LAV as a serious potential candidate for the treatment of NRP1/EGFR pathway-associated tumors.

Metabolomics profiling in predicting of post-herpetic neuralgia induced by varicella zoster.

To explore potential metabolomics biomarkers in predicting post-herpetic neuralgia (PHN) induced by herpes zoster (HZ). A total of 90 eligible patients were prospectively enrolled and assigned into an acute pain (ACP) group and a PHN group. Serum samples were collected before clinical intervention to perform metabolomics profiling analyses using gas chromatography mass spectrometry (GC-MS). Key metabolites were identified using partial least squares discriminant analysis (PLS-DA). A binary logistic regression was used to build a combined biomarker model to predict PHN from ACP. The discriminating efficiency of the combined biomarker model was investigated and validated by internal validation. Six metabolites were identified as the key metabolites related to PHN. All these metabolites (N-Acetyl-5-hydroxytryptaMine, glucose, dehydroascorbic acid, isopropyl-beta-D-thiogalactopyranoside, 1,5-anhydro-D-sorbitol, and glutamic acid) were found elevated in the PHN group. Pathway analyses showed that glucose-alanine cycle, tryptophan metabolism, tyrosine metabolism, lactose degradation, malate-aspartate shuttle were top five metabolic pathways evolved in PHN. The AUC was 0.85 (95% CI 0.76-0.93) for the combined biomarker model, and was 0.91 (95% CI 0.84-1.00) for the internal validation data set to predict PHN. Metabolomics analyses of key metabolites could be used to predict PHN induced by HZ.

Xanthine oxidase inhibitory kinetics and mechanism of ellagic acid: In vitro, in silico and in vivo studies.

Ellagic acid (EA), which is widely distributed in many foods, has been found to possess inhibitory activity against xanthine oxidase (XO). However, there is ongoing debate about the difference in XO inhibitory activity between EA and allopurinol. Additionally, the inhibitory kinetics and mechanism of EA on XO are still unclear. Herein, the authors systematically studied the inhibitory effects of EA on XO. The authors' findings showed that EA is a reversible inhibitor with mixed-type inhibition, and its inhibitory activity is weaker than allopurinol. Fluorescence quenching experiments suggested that the generation of EA-XO complex was exothermic and spontaneous. In silico analysis further confirmed that EA entered the XO catalytic centre. Furthermore, the authors verified the anti-hyperuricemia effect of EA in vivo. This study elucidates the inhibition kinetics and mechanism of EA on XO, and lays a theoretical foundation for the further development of drugs and functional foods containing EA for the treatment of hyperuricemia.

Circular RNA hsa_circ_0023404 promotes the proliferation, migration and invasion in endometrial cancer cells through regulating miR-217/MAPK1 axis.

BACKGROUND: Emerging studies indicated that circular RNA hsa_circ_ 0023404 and its target miR-217/MARK1 axis play a critical role in cancer progression such as non-small cell lung cancer and cervical cancer. However, the role of hsa_circ_0023404/miR-217/MARK1 involved in endometrial cancer (EC) was not investigated yet. The aim of this study is to investigate the functions of hsa_circ_0023404 in endometrial cancer (EC) and the potential molecular mechanism. METHODS: We used RT-qPCR and Western blot approach to detect the expressed levels of related genes in EC cell lines. Transfected siRNAs were applied to knockdown the level of related mRNA in cells. Cell proliferation by CCK-8 assay and colony formation assay were applied to detect cell proliferation. Transwell migration and invasion assay was for detecting the migration and invasion of the cells. RESULTS: RT-qPCR showed that the levels of hsa_circ_0023404 and MARK1 mRNA were upregulated, but mirR-217 was decreased in three endometrial cancer cell lines. Knockdown of hsa_circ_0023404 by siRNA markedly increased the level of miR-217 and reduced the proliferation of the Ishikawa cells. It also inhibited the cell migration and invasion. Anti-miR-217 can reverse the promoted proliferation, migrations and invasion of Ishikawa cells mediated by si-circ_0023404. si-MARK1 restored the inhibited cell proliferation, migration and invasion of the co-transfected Ishikawa cells with si- circ_0023404 and anti-miR-217. CONCLUSION: hsa_circ_0023404 exerts a tumor-promoting role in endometrial cancer by regulating miR-217/MARK1 axis. hsa_circ_0023404 inhibit miR-217 as sponge which inhibit endometrial cancer cell growth and metastasis. MARK1 is downstream target of miR217 and upregulated by hsa_circ_ 0023404/miR-217 axis and involved in the endometrial cancer progression.

Application of 3D reconstruction technology based on an improved MC algorithm in a shotcreting robot.

A shotcreting robot needs to reconstruct the arch surface in three dimensions (3D) during the process of spraying a tunnel. To solve this problem, we propose an improved marching cube (MC) reconstruction method based on a point cloud splice and normal re-orient. First, we use the explosion-proof LIDAR to acquire the point cloud data of the tunnel arch, followed by the use of the iterative closest point algorithm, a PassThrough filter, and a StatisticalOutlierRemoval filter for point cloud splicing, data segmentation, and simplification, respectively. In order to improve the reconstruction accuracy, we adjusted the estimated point cloud normal for normal consistency and obtained the geometric features of the complex point cloud surface. Furthermore, combined with the improved MC algorithm, the 3D reconstruction of the tunnel arch is realized. The experimental results show that the proposed method can reconstruct the 3D model of the tunnel arch surface quickly and accurately, which lays a foundation for further research on a trajectory plan, spraying status monitors, and control strategies.

Adverse drug reactions and correlations with drug-drug interactions: A retrospective study of reports from 2011 to 2020.

Introduction: Adverse drug reactions (ADRs) represent a public health problem worldwide that deserves attention due to the impact on mortality, morbidity, and healthcare costs. Drug-drug interactions (DDIs) are an important contributor to ADRs. Most of the studies focused only on potential DDIs (pDDIs), while the detailed data are limited regarding the ADRs associated with actual DDIs. Methods: This retrospective study evaluated ADRs reported between 2011 and 2020 in a tertiary hospital. The causality and severity of ADRs were evaluated through the Naranjo Algorithm and Hartwig's scale, respectively. Preventability classification was based on the modified Schoumock and Thornton scale. For ADRs with at least two suspected drugs, pDDIs were identified according to the Lexi-Interact. We further checked whether the ADR description in the reports corresponded to the clinical consequences of the pDDIs. Results: A total of 1,803 ADRs were reported, of which 36.77% ADRs were classified as mild, 43.26% as moderate, and 19.97% as severe. The assessment of causality showed that the distributions of definite, probable, and possible categories were 0.33%, 58.68%, and 40.99%, respectively. A total of 53.97% of ADRs were identified as preventable ADRs, while 46.03% were recognized as unpreventable. The severity of ADRs was significantly correlated with age, the number of suspected drugs and preventability. Antimicrobial agents were the most common implicated pharmacological group, and the most frequently affected system was the gastrointestinal system. Considering individual drugs, aspirin was the most frequently reported drug. Among 573 ADRs with at least two suspected drugs, 105 ADRs were caused by actual DDIs, of which only 59 and 6 ADRs were caused by actual DDIs in category D and X, respectively. The most frequent drugs involved in actual DDIs of category D were aspirin and heparin, with the majority of ADRs being gastrointestinal bleeding. Conclusion: This study analyzed the pattern of ADRs in detail and obtained clinical evidence about ADRs associated with actual DDIs. These findings may be useful to compare patterns between different centers and to design preventive strategies for ADRs. Continuous education and training should be provided for physicians regarding the knowledge and recognition of ADRs associated with DDIs.

Improved A* Path Planning Method Based on the Grid Map.

In obstacle spatial path planning, the traditional A* algorithm has the problem of too many turning points and slow search speed. With this in mind, a path planning method that improves the A* (A-Star) algorithm is proposed. The mobile robot platform was equipped with a lidar and inertial measurement unit (IMU). The Hdl_graph_slam mapping algorithm was used to construct a two-dimensional grid map, and the improved A* algorithm was used for path planning of the mobile robot. The algorithm introduced the path smoothing strategy and safety protection mechanism, and it eliminated redundant points and minimal corner points by judging whether there were obstacles in the connection of two path nodes. The algorithm effectively improved the smoothness of the path and facilitated the robot to move in the actual operation. It could avoid the wear of the robot by expanding obstacles and improving the safety performance of the robot. Subsequently, the algorithm introduced the steering cost model and the adaptive cost function to improve the search efficiency, making the search purposeful and effective. Lastly, the effectiveness of the proposed algorithm was verified by experiments. The average path search time was reduced by 13%. The average search extension node was reduced by 11%. The problems of too many turning points and slow search speed of traditional A* algorithm in path planning were improved.

Oncolytic virus expressing PD-1 inhibitors activates a collaborative intratumoral immune response to control tumor and synergizes with CTLA-4 or TIM-3 blockade.

BACKGROUND: Oncolytic viruses (OVs) are capable to inflame the tumor microenvironment (TME) and elicit infiltrating tumor-specific T cell responses. However, OV treatment negatively alters the cancer-immune set point in tumors to attenuate the antitumor immune response, which suggests the necessity of dissecting the immune landscape of the virus-treated tumors and developing novel strategies to maximize the potential of OVs. The aim of this study is to investigate the effect of the single-chain variable fragment (scFv)-armed OVs targeting PD-1 on the TME, and ultimately overcome localized immunosuppression to sensitize tumors to immunotherapies. METHODS: A tumor-selective oncolytic herpes simplex virus vector was engineered to encode a humanized scFv against human PD-1 (hPD-1scFv) (YST-OVH). The antitumor efficacy of YST-OVH was explored in multiple therapeutic mouse models. The neurotoxicity and safety of YST-OVH were evaluated in nonhuman primates. The precise dynamics in the TME involved in YST-OVH treatment were dissected using cytometry by time-of-flight (CyTOF). RESULTS: The identified hPD-1scFv showed superior T-cell activating activity. Localized delivery of hPD-1scFv by YST-OVH promotes systemic antitumor immunity in humanized PD-1 mouse models of established cancer. Immune profiling of tumors using CyTOF revealed the enhanced antitumor effect of YST-OVH, which largely relied on CD8+ T cell activity by augmenting the tumor infiltration of effector CD8+ T cells and establishment of memory CD8+ T cells and reducing associated CD8+ T cell exhaustion. Furthermore, YST-OVH treatment modified the cancer-immune set point of tumors coupled to coexpression of CTLA-4 and TIM-3 on exhausted CD8+ T cells and high levels of CTLA-4+ Treg cells. A combination approach incorporating anti-CTLA-4 or anti-TIM-3 further improved efficacy by increasing tumor immunogenicity and activating antitumor adaptive immune responses. Moreover, this therapeutic strategy showed no neurotoxicity and was well tolerated in nonhuman primates. The benefit of intratumoral hPD-1scFv expression was also observed in humanized mice bearing human cancer cells. CONCLUSION: Localized delivery of PD-1 inhibitors by engineered YST-OVH was a highly effective and safe strategy for cancer immunotherapy. YST-OVH also synergized with CTLA-4 or TIM-3 blockade to enhance the immune response to cancer. These data provide a strong rationale for further clinical evaluation of this novel therapeutic approach.

A potent neutralizing and protective antibody against a conserved continuous epitope on HSV glycoprotein D.

Infections caused by herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) remain a serious global health issue, and the medical countermeasures available thus far are limited. Virus-neutralizing monoclonal antibodies (NAbs) are crucial tools for studying host-virus interactions and designing effective vaccines, and the discovery and development of these NAbs could be one approach to treat or prevent HSV infection. Here, we report the isolation of five HSV NAbs from mice immunized with both HSV-1 and HSV-2. Among these were two antibodies that potently cross-neutralized both HSV-1 and HSV-2 with the 50% virus-inhibitory concentrations (IC50) below 200 ng/ml, one of which (4A3) exhibited high potency against HSV-2, with an IC50 of 59.88 ng/ml. 4A3 neutralized HSV at the prebinding stage and prevented HSV infection and cell-to-cell spread. Significantly, administration of 4A3 completely prevented weight loss and improved survival of mice challenged with a lethal dose of HSV-2. Using structure-guided molecular modeling combined with alanine-scanning mutagenesis, we observed that 4A3 bound to a highly conserved continuous epitope (residues 216 to 220) within the receptor-binding domain of glycoprotein D (gD) that is essential for viral infection and the triggering of membrane fusion. Our results provide guidance for developing NAb drugs and vaccines against HSV.

Efficacy and Safety of Banxia Formulae for Insomnia: A Systematic Review and Meta-Analysis of High-Quality Randomized Controlled Trials.

OBJECTIVE: To systematically evaluate the efficacy and safety of Banxia (Pinellia Tuber) formulae in the treatment of insomnia compared with those of conventional western medicines. METHODS: Randomized controlled trials (RCTs) evaluating the efficacy and safety of Banxia formulae in the treatment of insomnia were searched from the following databases: PubMed, Cochrane Library, EMBASE, the China National Knowledge Infrastructure (CNKI), Chinese Scientific Journals Database (VIP), and Wanfang database. The literature collected was from the time when the databases were established to April 2020. Quality assessment and meta-analysis were conducted by using Cochrane bias risk assessment tool and RevMan 5.2, respectively. Publication bias was assessed by Egger's test. RESULTS: Fourteen RCTs with 910 participants were identified. A total of 46 traditional Chinese medicines involving 2 different dosage forms were used in the included studies. Meta-analysis indicated that Banxia formulae had more significant effects on improving the total effective rate (RR = 1.23, 95% CI 1.16 to 1.31), Pittsburgh Sleep Quality Index (PSQI, MD = -1.05, 95% CI -1.63 to -0.47), and the TCM syndrome score (SMD = -0.78, 95% CI -1.18 to -0.39). Meanwhile, on reducing adverse events, Banxia formulae also showed an advantage (RR = 0.48, 95% CI 0.24 to 0.93). CONCLUSION: According to the current studies, the efficacy of Banxia formulae in the treatment of insomnia is better than that of the conventional western medicines, and its safety is relatively stable. However, due to the limitations of this study, further research and evaluation are needed.

Tumor-targeting oncolytic virus elicits potent immunotherapeutic vaccine responses to tumor antigens.

Oncolytic viruses represent a promising therapeutic modality, but they have yet to live up to their therapeutic potential. Safety and efficacy concerns impel us to identify least toxic oncolytic agents that would generate durable and multifaceted anti-tumor immune responses to disrupt the tumors. Here we describe a rational engineered oncolytic herpes virus (OVH) that is a selective killer for targeting tumors, has strong safety records, induces complete regression of tumors in multiple tumor models, and elicits potent antitumor immunity. By far, the potential of OVs in promoting the tumor antigen-specific humoral immune responses remains obscure. In this study, we found that effective treatment by OVH induced immunogenic cell death, which facilitates to elicit humoral immune responses. Depletion experiments revealed that B cells were required for maximal antitumor efficacy of oncolytic immunotherapy. Both serum transfer and antibody treatment experiments revealed that endogenous oncolysis-induced antigen-targeting therapeutic antibodies can lead to systemic tumor regression. Our data demonstrate that tumor-targeting immune modulatory properties confer oncolytic OVH virotherapy as potent immunotherapeutic cancer vaccines that can generate specific and efficacious antitumor humoral responses by eliciting endogenous tumor antigen-targeting therapeutic antibodies in situ, resulting in an efficacious and tumor-specific therapeutic effect.

[Application of 3S Techniques to Regional Survey of Chinese Materia Medica Resources].

Objective: To explore the application of 3S techniques to regional survey of Chinese materia medica resources, in order to provide technical reference for the fourth national survey of Chinese materia medica resources. Methods: Based on remote sensing technology, satellite positioning technology and GIS technology, GPS position indicator, SLR camera and related software such as Google Earth, HOLUX ez Tour for Logger and XTTools were used to establish the application model of 3S techniques for the regional survey of Chinese materia medica resources. Results: The application model established in field survey performed well in pathway expedition and sample plot survey. It also matched the digital images of Chinese herbs with their geographic information efficiently and did statistical analysis effectively on survey result. Conclusion: It is suggested that the application of 3S techniques to regional survey of Chinese meteria medica resources is beneficial to improve efficiency of the survey and obtain more accurate geographic information for sharing and dynamic monitoring.

BuShenYiQi granule inhibits atopic dermatitis via improving central and skin Hypothalamic-Pituitary-Adrenal axis function.

BACKGROUND: Dysfunction of central and skin Hypothalamic-Pituitary-Adrenal (HPA) axis play important roles in pathogenesis of atopic dermatitis (AD). Our previous studies showed that several Chinese herbs could improve HPA axis function. In this study, we evaluated the anti-inflammatory effects of BuShenYiQi granule (BSYQ), a Chinese herbs formula, in AD mice and explored the effective mechanism from regulation of HPA axis. METHODS: The ovalbumin (OVA) induced AD mice model were established and treated with BSYQ. We evaluated dermatitis score and histology analysis of dorsal skin lesions, meanwhile, serum corticosterone (CORT), adrenocorticotropic hormone (ACTH), corticotropin-releasing hormone (CRH) and inflammatory cytokines were determined by ELISA. The changes of CRH/proopiomelanocortin(POMC) axis elements, corresponding functional receptors and crucial genes of glucocorticosteroidogenesis in the skin were measured by quantitative real-time PCR and western blot, respectively. RESULTS: The symptoms and pathological changes in skin of AD mice were significantly improved and several markers of inflammation and allergy descended obviously after BSYQ treatment. We found that AD mice had insufficient central HPA tone, but these conditions were markedly improved after BSYQ treatment. The AD mice also showed a disturbed expression of skin HPA. In lesion skin of AD mice, the mRNA and protein expressions of CRH decreased significantly, on the contrary, POMC and cytochrome P450 side-chain cleavage enzyme (CYP11A1) increased markedly, meanwhile, NR3C1 (mouse GR), CRHR2 and 11-hydroxylase type 1(CYP11B1) were reduced locally. Most of these tested indexes were improved after BSYQ treatment. CONCLUSIONS: AD mice displayed the differential expression pattern of central and skin HPA axis and BSYQ treatment significantly alleviated the symptoms of AD mice and presented anti-inflammatory and anti-allergic effects via regulating the expression of central and skin HPA axis.

A Subsequent Human Neural Progenitor Transplant into the Degenerate Retina Does Not Compromise Initial Graft Survival or Therapeutic Efficacy.

PURPOSE: Stem and progenitor cell transplantation provides a promising clinical application for treating degenerative retinal diseases, including age-related macular degeneration (AMD) and retinitis pigmentosa (RP). Our previous studies have shown that a single subretinal injection of human cortical-derived neural progenitor cells (hNPCctx) into cyclosporine-treated Royal College of Surgeons (RCS) rats preserved both photoreceptors and visual function. However, it is still unknown whether nonautologous progenitor cell readministration for sustained vision is efficacious and safe in terms of the initial graft initiating an immune response to a subsequent graft. METHODS: A cell suspension containing 3×104 hNPCctx into one eye of cyclosporine-treated RCS rats at postnatal day 21 (P21), followed by a second transplantation at P95 into the previously untreated fellow eye. RESULTS: hNPCctx delayed photoreceptor degeneration and preserved visual function, as measured by electroretinography (ERG), optokinetic response (OKR), and luminance threshold recordings (LTRs). Visual function and photoreceptors of the initially treated eye were still preserved 6 weeks after hNPCctx were injected into the second eye. Antibodies against T-cell markers showed that CD3, CD4, and CD8 T cells were not detected at P90 and P140 in most cases. No detectable level of anti-nestin antibody was found in serum by enzyme-linked immunosorbent assay (ELISA). CONCLUSIONS: This xenograft study with cyclosporine-treated animals demonstrates that readministration of hNPCctx into the fellow eye did not induce anti-graft immune responses or lower therapeutic efficacy of hNPCctx in preserving vision. Thus, readministration of progenitor cells to sustain long-term efficacy may be an option for long-term therapies of retinal degeneration. TRANSLATIONAL RELEVANCE: Redosing neural progenitors do not affect the efficacy of the initial grafts in protecting vision or induce unwanted immune responses.

Design, Development, and Initial Evaluation of a Terminology for Clinical Decision Support and Electronic Clinical Quality Measurement.

When coupled with a common information model, a common terminology for clinical decision support (CDS) and electronic clinical quality measurement (eCQM) could greatly facilitate the distributed development and sharing of CDS and eCQM knowledge resources. To enable such scalable knowledge authoring and sharing, we systematically developed an extensible and standards-based terminology for CDS and eCQM in the context of the HL7 Virtual Medical Record (vMR) information model. The development of this terminology entailed three steps: (1) systematic, physician-curated concept identification from sources such as the Health Information Technology Standards Panel (HITSP) and the SNOMED-CT CORE problem list; (2) concept de-duplication leveraging the Unified Medical Language System (UMLS) MetaMap and Metathesaurus; and (3) systematic concept naming using standard terminologies and heuristic algorithms. This process generated 3,046 concepts spanning 68 domains. Evaluation against representative CDS and eCQM resources revealed approximately 50-70% concept coverage, indicating the need for continued expansion of the terminology.