Characterization of Insufficiency Fracture and Bone Metastasis After Radiotherapy in Patients With Cervical Cancer Detected by Bone Scan: Role of Magnetic Resonance Imaging

Background: Insufficiency fracture (IF) can show increased uptake on a bone scan (BS). IFs are often misinterpreted as bone metastases if the characteristic “Honda sign” (H-sign) is invisible. The purpose of the present study was to evaluate the utility of magnetic resonance imaging (MRI) alone for the characterization of IF and bone metastasis after radiotherapy in patients with cervical cancer detected by BS.Materials and Methods: Our study included 40 patients with cervical cancer after radiotherapy that showed pelvic emerging increased uptake on a BS during follow-up. Then further MRI examination was performed in all patients. Two radiologists independently reviewed the MR images, and the sensitivity, specificity and accuracy were calculated based on the mean scores. Diagnostic validity of the inter-observer was calculated by using kappa statistics. The gold standard was based on radiologic findings, clinical data and follow-up at least 12 months.Results: A total of 57 emerging bone lesions detected at BS were identified in the reference standard, including 43 IFs and 14 bone metastases. Only 20 patients showed a “H-sign” on the BS images. Using MRI analysis, all lesions detected by BS were found in MRI by both radiologists. On average, the sensitivity, specificity, and accuracy for distinguishing IFs from bone metastases were 95.3% (41/43), 92.8% (13/14), and 94.7% (54/57), respectively. The inter-observer variability was determined to be very good (kappa value = 0.962).Conclusions: MRI is a reliable diagnostic technique for the further characterization of emerging lesions detected by BS, MRI shows great diagnostic efficiency in the differentiation of IF and bone metastasis

HIV Antigen Incorporation within Adenovirus Hexon Hypervariable 2 for a Novel HIV Vaccine Approach

Adenoviral (Ad) vectors have been used for a variety of vaccine applications including cancer and infectious diseases. Traditionally, Ad-based vaccines are designed to express antigens through transgene expression of a given antigen. However, in some cases these conventional Ad-based vaccines have had sub-optimal clinical results. These sub-optimal results are attributed in part to pre-existing Ad serotype 5 (Ad5) immunity. In order to circumvent the need for antigen expression via transgene incorporation, the “antigen capsid-incorporation” strategy has been developed and used for Ad-based vaccine development in the context of a few diseases. This strategy embodies the incorporation of antigenic peptides within the capsid structure of viral vectors. The major capsid protein hexon has been utilized for these capsid incorporation strategies due to hexon's natural role in the generation of anti-Ad immune response and its numerical representation within the Ad virion. Using this strategy, we have developed the means to incorporate heterologous peptide epitopes specifically within the major surface-exposed domains of the Ad capsid protein hexon. Our study herein focuses on generation of multivalent vaccine vectors presenting HIV antigens within the Ad capsid protein hexon, as well as expressing an HIV antigen as a transgene. These novel vectors utilize HVR2 as an incorporation site for a twenty-four amino acid region of the HIV membrane proximal ectodomain region (MPER), derived from HIV glycoprotein gp41 (gp41). Our study herein illustrates that our multivalent anti-HIV vectors elicit a cellular anti-HIV response. Furthermore, vaccinations with these vectors, which present HIV antigens at HVR2, elicit a HIV epitope-specific humoral immune response

An Augmented Reality-Assisted Prognostics and Health Management System Based on Deep Learning for IoT-Enabled Manufacturing

With increasingly advanced Internet of Things (IoT) technology, the composition of workshop equipment has become more and more complex. Based on this, the rate of system performance degradation and the probability of fault have both increased. Owing to this, not only has the difficulty of constructing the remaining useful life (RUL) model increased but also the improvement in speed of maintenance personnel cannot keep up with the speed of equipment replacement. Therefore, an augmented reality (AR)-assisted prognostics and health management system based on deep learning for IoT-enabled manufacturing is proposed in this paper. Firstly, the feature extraction model based on Convolutional Neural Network-Particle Swarm Optimization (PSO-CNN) is proposed with the purpose of excavating the internal associations in large amounts of production data. Based on this, the high-accuracy RUL prediction is accomplished by Gate Recurrent Unit (GRU)-attention, which can capture the long-term and short-term dependencies of time series and successfully solve the gradient disappearance problem of RNN. Moreover, more attention will be paid to important content with the help of the attention mechanism. Additionally, high-efficiency maintenance guidance and visible instructions can be accomplished by AR. On top of this, the remote expert can offer help when maintenance personnel encounters tough problems. Finally, a real case was implemented in a typical IoT-enabled workshop, which validated the effectiveness of the proposed approach

Elevated number and density of macrophage-like cell as a novel inflammation biomarker in diabetic macular edema

Abstract To quantitatively analyze the number and density of macrophage-like cells (MLCs) at the vitreoretinal interface at macular region in diabetic retinopathy (DR) with and without diabetic macular edema (DME). This cross-sectional study involved 240 eyes of 146 treatment-naïve DR patients, including 151 eyes with DME. The number and density of MLCs were analyzed quantitatively using optical coherence tomography angiography (OCTA) and were compared between DME and non-DME eyes as well as proliferative DR (PDR) and non-PDR (NPDR) eyes. Correlation between MLCs density and vessel density of macular superficial capillary plexus (SCP) at macular region was evaluated. The number and density of macular MLCs were both elevated in DME group compared to non-DME group (all p < 0.001). The morphology of MLCs in DME eyes appeared larger and fuller. NPDR eyes had higher number and density of MLCs (p = 0.027 and 0.026), greater central macular thickness (CMT) (p = 0.002) and vessel density than PDR eyes in non-DME group but comparable to PDR eyes in DME group. The number and density of MLCs at macular region were significantly higher with larger and fuller morphology in DR patients with DME than those without DME. PDR eyes had fewer MLCs than NPDR eyes for DR eyes without DME

Comparison of efficacy and safety of intravitreal ranibizumab and conbercept before vitrectomy in Chinese proliferative diabetic retinopathy patients: a prospective randomized controlled trial

Abstract Background To compare the efficacy and safety of preoperative intravitreal injections of ranibizumab and conbercept in Chinese proliferative diabetic retinopathy (PDR) patients. Methods This prospective randomized controlled trial enrolled 90 eyes of 80 patients with PDR. Forty-four eyes of 40 patients that received intravitreal ranibizumab (IVR) injections (0.5 mg/0.05 mL) before vitreous surgeries were assigned to the IVR group. Forty-six eyes of 40 patients that received intravitreal conbercept (IVC) injections (0.5 mg/0.05 mL) before vitreous surgeries were assigned to the IVC group. Intraoperative and postoperative indices were assessed for further comparison between the two groups. Results There were no statistically significant differences in all surgery indices, including intraoperative indices (surgery time, P = 0.225; intraoperative bleeding, P = 0.808; endodiathermy use, P = 0.693; incidence of iatrogenic retinal breaks, P = 0.740; relaxing retinotomy, P = 0.682; retinal reattachment, P = 0.682 and silicone oil tamponade, P = 0.814) and postoperative indices (postoperative vitreous hemorrhage (VH), P = 0.808; neovascular glaucoma (NVG), P = 0.964; recurrent retinal detachment, P = 0.531; postoperative fibrovascular proliferation progression, P = 0.682 and reoperation, P = 0.955) between the two groups. There were no statistically significant differences in best-corrected visual acuity (BCVA) at each follow-up visit (P = 0.939, 0.669, 0.741 and 0.717, respectively) or in central retinal thickness (CRT) (P = 0.976, 0.699, 0.551 and 0.686, respectively). As for safety profile, both groups had no ocular or system adverse events during the observation period. Conclusions IVR and IVC as a pretreatment of vitrectomy had similar efficacy and safety profile for Chinese PDR patients. Trial registration: Registered at ClinicalTrials.gov ( NCT05414149 )

Mucosal Priming with a Replicating-Vaccinia Virus-Based Vaccine Elicits Protective Immunity to Simian Immunodeficiency Virus Challenge in Rhesus Monkeys

Mucosal surfaces are not targeted by most human immunodeficiency virus type 1 (HIV-1) vaccines, despite being major routes for HIV-1 transmission. Here we report a novel vaccination regimen consisting of a mucosal prime with a modified replicating vaccinia virus Tiantan strain (MVTT(SIVgpe)) and an intramuscular boost with a nonreplicating adenovirus strain (Ad5(SIVgpe)). This regimen elicited robust cellular immune responses with enhanced magnitudes, sustainability, and polyfunctionality, as well as higher titers of neutralizing antibodies against the simian immunodeficiency virus SIV(mac1A11) in rhesus monkeys. The reductions in peak and set-point viral loads were significant in most animals, with one other animal being protected fully from high-dose intrarectal inoculation of SIV(mac239). Furthermore, the animals vaccinated with this regimen were healthy, while ∼75% of control animals developed simian AIDS. The protective effects correlated with the vaccine-elicited SIV-specific CD8(+) T cell responses against Gag and Pol. Our study provides a novel strategy for developing an HIV-1 vaccine by using the combination of a replicating vector and mucosal priming

A Single Injection of Human Neutralizing Antibody Protects against Zika Virus Infection and Microcephaly in Developing Mouse Embryos

Summary: Zika virus (ZIKV) is a mosquito-transmitted flavivirus that is generally benign in humans. However, an emergent strain of ZIKV has become widespread, causing severe pre- and post-natal neurological defects. There is now an urgent need for prophylactic and therapeutic agents. To address this, we investigated six human monoclonal antibodies with ZIKV epitope specificity and neutralizing activity in mouse models of ZIKV infection and microcephaly. A single intraperitoneal injection of these antibodies conveyed distinct levels of adult and in utero protection from ZIKV infection, which closely mirrored their respective in vitro neutralizing activities. One antibody, ZK2B10, showed the most potent neutralization activity, completely protected uninfected mice, and markedly reduced tissue pathology in infected mice. Thus, ZK2B10 is a promising candidate for the development of antibody-based interventions and informs the rational design of ZIKV vaccine. : Zika virus (ZIKV) is a mosquito-transmitted flavivirus that can cause severe neurological defects in humans. Li et al. have identified a human monoclonal antibody capable of protection against ZIKV infection and related diseases when tested in mouse models. This antibody serves as a promising candidate for clinical development against ZIKV. Keywords: Zika virus, microcephaly, neutralizing antibody, epitope, vaccine, neural progenitor cells, protectio