Immune cell targeting nanoparticles: a review

Abstract Immune cells are attractive targets for therapy as they are direct participants in a variety of diseases. Delivering a therapeutic agent only to cells that act on a disease by distinguishing them from other cells has the advantage of concentrating the therapeutic effect and lowering systemic side effects. Distinguishing each immune cell from other immune cells to deliver substances, including drugs and genes, can be achieved using nanotechnology. And alsonanoparticles can ensure in vivo stability and sustained drug release. In addition, there is an ease of surface modification, which is an important characteristic that can be utilized in targeted drug delivery systems. This characteristic allows us to utilize various properties that are specifically expressed in each immune cell. A number of studies have delivered various substances specifically to immune cells through surface engineering with active target ligands that can target each immune cell and enzyme-responsive coating, and demonstrated high therapeutic effects compared to conventional treatments. Progress in research on target delivery has been suggested to be a breakthrough for the treatments of various diseases, including cancer treatment

Label-Noise Robust Diffusion Models

Conditional diffusion models have shown remarkable performance in various generative tasks, but training them requires large-scale datasets that often contain noise in conditional inputs, a.k.a. noisy labels. This noise leads to condition mismatch and quality degradation of generated data. This paper proposes Transition-aware weighted Denoising Score Matching (TDSM) for training conditional diffusion models with noisy labels, which is the first study in the line of diffusion models. The TDSM objective contains a weighted sum of score networks, incorporating instance-wise and time-dependent label transition probabilities. We introduce a transition-aware weight estimator, which leverages a time-dependent noisy-label classifier distinctively customized to the diffusion process. Through experiments across various datasets and noisy label settings, TDSM improves the quality of generated samples aligned with given conditions. Furthermore, our method improves generation performance even on prevalent benchmark datasets, which implies the potential noisy labels and their risk of generative model learning. Finally, we show the improved performance of TDSM on top of conventional noisy label corrections, which empirically proving its contribution as a part of label-noise robust generative models. Our code is available at: https://github.com/byeonghu-na/tdsm.Comment: Accepted at ICLR 202

Leadership Succession Planning: An Examination of Sole Proprietor Estate Surveying and Valuation Firms in Lagos Metropolis, Nigeria

This paper reports the results from a survey of 38 small sole- proprietor estate surveying and valuation firms in Lagos, Nigeria. A 45% questionnaire retrieval rate was achieved while CEOs/owners of estate surveying and valuation firms were interviewed. Descriptive statistics were used to analyze the respondents‟ general characteristics as well as their attitude toward business succession planning. The study found that sole-proprietor firm owners desired that their firms outlive them through transferring of the firms‟ businesses to their next generation. However, majority of these sole proprietors‟ next generation were not keen on pursuing real estate business related courses in their undergraduate days in view of their exposure to modern technology and the influence of peers. Also, the study found that the owners of these firms have not, as a matter of policy, planned for their succession because of the cultural and attitudinal beliefs and values, which forbid thoughts about death or incapacitation about a living soul. As a result, the study indicated that only 5% of sole proprietor estate surveying and valuation firms in this category have continued to the second generation in the study area. This outcome has serious implications for small professional service businesses‟ economic and job creation potential for Nigeria

Clinical significance of amyloid β positivity in patients with probable cerebral amyloid angiopathy markers

Purpose: We investigated the frequency and clinical significance of amyloid β (Aβ) positivity on PET in patients with cerebral amyloid angiopathy (CAA). / Methods: We recruited 65 patients who met the modified Boston criteria for probable CAA. All underwent amyloid PET, MRI, APOE genotyping and neuropsychological testing, and we obtained information on MRI markers of CAA and ischemic cerebral small-vessel disease (CSVD). We investigated the CAA/ischemic CSVD burden and APOE genotypes in relation to Aβ positivity and investigated the effect of Aβ positivity on longitudinal cognitive decline. / Results: Among the 65 CAA patients, 43 (66.2%) showed Aβ PET positivity (Aβ+). Patients with Aβ+ CAA had more lobar microbleeds (median 9, interquartile range 2–41, vs. 3, 2–8; P = 0.045) and a higher frequency of cortical superficial siderosis (34.9% vs. 9.1%; P = 0.025), while patients with Aβ− CAA had more lacunes (1, 0–2, vs. 0, 0–1; P = 0.029) and a higher frequency of severe white matter hyperintensities (45.5% vs. 20.9%; P = 0.040). The frequency of ε4 carriers was higher in Aβ+ patients (57.1%) than in Aβ− patients (18.2%; P = 0.003), while the frequency of ε2 carriers did not differ between the two groups. Finally, Aβ positivity was associated with faster decline in multiple cognitive domains including language (P < 0.001), visuospatial function (P < 0.001), and verbal memory (P < 0.001) in linear mixed effects models. / Conclusion: Our findings suggest that a significant proportion of patients with probable CAA in a memory clinic are Aβ− on PET. Aβ positivity in CAA patients is associated with a distinct pattern of CSVD biomarker expression, and a worse cognitive trajectory. Aβ positivity has clinical relevance in CAA and might represent either advanced CAA or additional Alzheimer’s disease neuropathological changes

The determination of dark adaptation time using electroretinography in conscious Miniature Schnauzer dogs

The optimal dark adaptation time of electroretinograms (ERG's) performed on conscious dogs were determined using a commercially available ERG unit with a contact lens electrode and a built-in light source (LED-electrode). The ERG recordings were performed on nine healthy Miniature Schnauzer dogs. The bilateral ERG's at seven different dark adaptation times at an intensity of 2.5 cd·s/m2 was performed. Signal averaging (4 flashes of light stimuli) was adopted to reduce electrophysiologic noise. As the dark adaptation time increased, a significant increase in the mean a-wave amplitudes was observed in comparison to base-line levels up to 10 min (p < 0.05). Thereafter, no significant differences in amplitude occured over the dark adaptation time. Moreover, at this time the mean amplitude was 60.30 ± 18.47 µV. However, no significant changes were observed for the implicit times of the a-wave. The implicit times and amplitude of the b-wave increased significantly up to 20 min of dark adaptation (p < 0.05). Beyond this time, the mean b-wave amplitudes was 132.92 ± 17.79 µV. The results of the present study demonstrate that, the optimal dark adaptation time when performing ERG's, should be at least 20 min in conscious Miniature Schnauzer dogs

Unilateral Psoriasis in a Woman with Ipsilateral Post-Mastectomy Lymphedema

Psoriasis is a multi-factorial disease with various clinical manifestations. We present a case of unilateral psoriasis associated with ipsilateral lymphedema that developed after mastectomy for breast cancer. A 42-year-old Korean woman was referred to our clinic with a 1-month history of multiple erythematous scaly patches on the right arm, back, and breast and was diagnosed with psoriasis by a skin biopsy. Three years previously, she had been diagnosed with breast cancer (T1N2), underwent a right quadrantectomy and axillary lymph node dissection, and completed adjuvant chemotherapy followed by high-dose adjuvant radiotherapy. She had started rehabilitation therapy on the right arm for secondary lymphedema 30 months previously. Because of the long interval between radiation and psoriasis, we speculated that changes in the local milieu caused by the lymphedema might be a causative factor. We hereby report a rare case of unilateral psoriasis following post-mastectomy lymphedema

Localized versus 360-degree laser photocoagulation with limited pars plana vitrectomy in the management of primary rhegmatogenous retinal detachment

Abstract Background To compare the efficacy of intraoperative localized and 360-degree laser photocoagulation in 23-gauge limited pars plana vitrectomy (PPV) for rhegmatogenous retinal detachment (RRD). Methods This retrospective, comparative, consecutive, interventional study included 155 eyes of 155 patients who underwent primary repair of RRD utilizing 23-gauge PPV with at least six months of follow up. Medical records were retrospectively reviewed, and the corresponding demographic data, preoperative ophthalmic features, surgical management, and postoperative course were recorded. Main outcome measures included single surgery anatomical success, pre- and post-operative visual acuity, and complications. Results Eighty-three patients (group A) received localized laser photocoagulation in PPV, while the remaining 72 patients (group B) received underwent circumferential 360-degree laser photocoagulation in PPV. Two skilled-surgeons performed all the surgeries, and 23-gauge PPV instrumentation, a wide-angle viewing system, endolaser photocoagulation, and gas tamponade were used in each case. No significant difference was identified in baseline characteristics. The single surgery anatomical success rate was 96.4 % in group A, and 95.8 % in group B, showing no significant difference (p = 1.00). Primary anatomical failure was caused by re-detachment due to break in 2 eyes in each group (no new break 1 eye, new break 1eye in group A, 2 eyes with no new break in group B), and proliferative vitreoretinopathy in 1 eye in each group. Other complications were epiretinal membrane in 7 eyes (3 in group A, 4 in group B), and macular hole in 1 eye in group B. There were no differences in pre- and post-operative best-corrected visual acuity (BCVA) as well as BCVA improvement (p=0.144, p=0.866 and p=0.263, respectively). Conclusion Localized laser photocoagulation showed no difference in anatomic and visual outcome in RRD patients, when compared with 360-degree laser photocoagulation in limited PPV. Routine circumferential 360-degree laser photocoagulation may not be necessary in vitrectomy surgery for primary rhegmatogenous retinal detachment without severe PVR

A case of congenital bilateral coronary-to-right ventricle fistula coexisting with variant angina

A coronary arteriovenous (AV) fistula consists of a communication between a coronary artery and a cardiac chamber, a great artery or the vena cava. It is the most common anomaly that can affect coronary perfusion. Yet bilateral involvement of a coronary fistula, constitutes an uncommon subgroup of coronary AV fistulas. We herein report on a case of bilateral coronary AV fistula that was coexistent with variant angina originating from the distal right ventricular branch of the right coronary artery and the distal septal branch of the left anterior descending artery, and the latter drained into the right ventricle

Impact of the conjugation of antibodies to the surfaces of polymer nanoparticles on the immune cell targeting abilities

Antibodies have been widely used to provide targeting ability and to enhance bioactivity owing to their high specificity, availability, and diversity. Recent advances in biotechnology and nanotechnology permit site-specific engineering of antibodies and their conjugation to the surfaces of nanoparticles (NPs) in various orientations through chemical conjugations and physical adhesions. This study proposes the conjugation of poly(lactic-co-glycolic acid) (PLGA) NPs with antibodies by using two distinct methods, followed by a comparison between the cell-targeting efficiencies of both techniques. Full-length antibodies were conjugated to the PLGA-poly(ethylene glycol)-carboxylic acid (PLGA-PEG-COOH) NPs through the conventional carbodiimide coupling reaction, and f(ab′)2 antibody fragments were conjugated to the PLGA-poly(ethylene glycol)-maleimide(PLGA-PEG-Mal) NPs through interactions between the f(ab′)2 fragment thiol groups and the maleimide located on the nanoparticle surface. The results demonstrate that the PLGA nanoparticles conjugated with the f(ab′)2 antibody fragments had a higher targeting efficiency in vitro and in vivo than that of the PLGA nanoparticles conjugated with the full-length antibodies. The results of this study can be built upon to design a delivery technique for drugs through biocompatible nanoparticles.This work was supported by the National Research Foundation of Korea (NRF) Grant funded by the Korean government (MSIT) (NRF-2019R1A4A1028700 and NRF-2019R1C1C1006300). This work was supported by the Fourth Stage of Brain Korea 21 Project of the Department of Intelligent Precision Healthcare and IBS-R015-D1

Growth differentiation factor 11 locally controls anterior-posterior patterning of the axial skeleton.

Growth and differentiation factor 11 (GDF11) is a transforming growth factor β family member that has been identified as the central player of anterior-posterior (A-P) axial skeletal patterning. Mice homozygous for Gdf11 deletion exhibit severe anterior homeotic transformations of the vertebrae and craniofacial defects. During early embryogenesis, Gdf11 is expressed predominantly in the primitive streak and tail bud regions, where new mesodermal cells arise. On the basis of this expression pattern of Gdf11 and the phenotype of Gdf11 mutant mice, it has been suggested that GDF11 acts to specify positional identity along the A-P axis either by local changes in levels of signaling as development proceeds or by acting as a morphogen. To further investigate the mechanism of action of GDF11 in the vertebral specification, we used a Cdx2-Cre transgene to generate mosaic mice in which Gdf11 expression is removed in posterior regions including the tail bud, but not in anterior regions. The skeletal analysis revealed that these mosaic mice display patterning defects limited to posterior regions where Gdf11 expression is deficient, whereas displaying normal skeletal phenotype in anterior regions where Gdf11 is normally expressed. Specifically, the mosaic mice exhibited seven true ribs, a pattern observed in wild-type (wt) mice (vs. 10 true ribs in Gdf11-/- mice), in the anterior axis and nine lumbar vertebrae, a pattern observed in Gdf11 null mice (vs. six lumbar vertebrae in wt mice), in the posterior axis. Our findings suggest that GDF11, rather than globally acting as a morphogen secreted from the tail bud, locally regulates axial vertebral patterning