Predicting slight freezing of gait in Parkinson's disease with anticipatory postural adjustments and limits of stability.

INTRODUCTION: Gait initiation (GI) includes automatic and voluntary movements. However, research on their impact on the first step in patients with Parkinson's disease (PD) and their relationship to freezing of gait (FOG) is lacking. We examined the effects of automatic movements (anticipatory postural adjustments [APAs]) and voluntary movements (limits of stability [LOS]) on the first step (first-step duration and first-step range of motion), along with their early recognition and prediction of slight FOG. METHODS: Twenty-three patients with PD and slight freezing (PD + FOG) and 25 non-freezing patients with PD (PD-FOG) were tested while off medications and compared with 24 healthy controls (HC). All participants completed a 7-m Stand and Walk Test (7 m SAW) and wore inertial sensors to quantify the APAs and first step. LOS was quantified by dynamic posturography in different directions using a pressure platform. We compared differences among all three groups, analysed correlations, and evaluated their predictive value for slight FOG. RESULTS: In PD + FOG, APAs and LOS were worse than those in the PD-FOG and HC groups (p < 0.001), and the first step was worse than that in HC (p < 0.001). APAs were correlated mainly with the first-step duration. APAs and LOS were correlated with the first-step range of motion. APAs have been recognized as independent predictors of FOG, and their combination with LOS enhances predictive sensitivity. CONCLUSION: APAs and LOS in patients with PD directly affect the first step during GI. In addition, the combination of APAs and LOS helped predict slight FOG.

Tumor Segmentation in Intraoperative Fluorescence Images Based on Transfer Learning and Convolutional Neural Networks.

OBJECTIVE: To propose a transfer learning based method of tumor segmentation in intraoperative fluorescence images, which will assist surgeons to efficiently and accurately identify the boundary of tumors of interest. METHODS: We employed transfer learning and deep convolutional neural networks (DCNNs) for tumor segmentation. Specifically, we first pre-trained four networks on the ImageNet dataset to extract low-level features. Subsequently, we fine-tuned these networks on two fluorescence image datasets (ABFM and DTHP) separately to enhance the segmentation performance of fluorescence images. Finally, we tested the trained models on the DTHL dataset. The performance of this approach was compared and evaluated against DCNNs trained end-to-end and the traditional level-set method. RESULTS: The transfer learning-based UNet++ model achieved high segmentation accuracies of 82.17% on the ABFM dataset, 95.61% on the DTHP dataset, and 85.49% on the DTHL test set. For the DTHP dataset, the pre-trained Deeplab v3 + network performed exceptionally well, with a segmentation accuracy of 96.48%. Furthermore, all models achieved segmentation accuracies of over 90% when dealing with the DTHP dataset. CONCLUSION: To the best of our knowledge, this study explores tumor segmentation on intraoperative fluorescent images for the first time. The results show that compared to traditional methods, deep learning has significant advantages in improving segmentation performance. Transfer learning enables deep learning models to perform better on small-sample fluorescence image data compared to end-to-end training. This discovery provides strong support for surgeons to obtain more reliable and accurate image segmentation results during surgery.

Safety and Efficacy of Early Rehabilitation After Stroke Using Mechanical Thrombectomy: A Pilot Randomized Controlled Trial.

Background: Early rehabilitation (ER) has been reported to be both safe and feasible for patients' post-stroke. To date, however, ER-related outcomes concerning patients who have undergone mechanical thrombectomy (MT) have not been investigated. This study aimed to determine the feasibility of ER and whether it improves prognosis in such patients. Methods: In this single-center, double-blinded, randomized controlled study involving 103 patients who met the study criteria (i.e., has undergone MT), we randomly divided patients (1:1) into ER and conventional rehabilitation groups. The primary outcome was mortality, while secondary outcomes included favorable outcomes (modified Rankin scale of 0-2), the incidence of non-fatal complications, and Barthel Index (BI) scores. We assessed outcomes at 3 months and 1-year post-stroke. Results: No significant between-group differences were found in terms of mortality and favorable outcomes at 3 months and 1-year post-stroke. At 3 months, 15 (28.8%) patients in the ER group and 29 (56.9%) in the conventional rehabilitation group (p = 0.002) had non-fatal complications. The BI in the ER and conventional rehabilitation groups was 100 (85-100) and 87.5 (60-100), respectively, (p = 0.007). At 1 year, the incidence of non-fatal complications was similar between both groups [BI in the ER group, 100 (90-100), p = 0.235; BI in the conventional rehabilitation group, 90 (63.8-100); p = 0.003]. Conclusion: Early rehabilitation (ER) reduces the incidence of early immobility-related complications and effectively improves patients' activities of daily living on a short- and long-term basis. Our results indicate that MT contributes to ER in patients with stroke. Clinical Trial Registration: www.chictr.org.cn, identifier: ChiCTR1900022665.

Characteristics of frailty phenotype in Chinese nursing home population and significance of motor function indicators in frailty assessment.

The objectives of this study were to analyze the distribution characteristics of frailty phenotypes in older adults of Chinese nursing homes, and to compare some motor function characteristics of older adults in nursing homes between frailty and non-frailty, to determine which motor function and frailty are related. This cross-sectional study included 177 older adults living in nursing homes. Frailty was diagnosed by Fried's phenotype, and motor function assessment characteristics (including muscle tone, ROM, and balance) were also evaluated. Chi-square and logistic regression analyses were performed. Frailty prevalence was 53% in nursing homes in big Chinese cities (average age 82.0 ±â€…6.1). Low levels of physical activity (90.4% in frail elder), decreased handgrip strength (98.9% in frail elder) and slowed walking speed (100% in frail elder) were the 3 main components of the frailty phenotype of frail adults in nursing homes in China. It is worth noting that 74.7% of the non-frail elders also had reduced handgrip strength. Further analysis showed that balance (P < .001), muscle tone (upper, P = .028, lower, P = .001) and the range of motion (P < .001) were associated with frailty in older adults. The frailty of the elders in Chinese nursing homes was characterized by the decline of motor function. And surprisingly, both frail and non-frail elders were found to have poor strength. Frail nursing home seniors also have body muscle tone, range of motion and balance problems. The elderly of China should focus on strength, stretch and balance training to improve motor function, especially strength training, which is important for prevention frailty.

Automated high-throughput preparation and characterization of oligonucleotide-loaded lipid nanoparticles.

Lipid nanoparticles (LNPs) are increasingly employed to improve delivery efficiency and therapeutic efficacy of nucleic acids. Various formulation parameters can affect the quality attributes of these nanoparticle formulations, but currently there is a lack of systemic screening approaches to address this challenge. Here, we developed an automated high-throughput screening (HTS) workflow for streamline preparation and analytical characterization of LNPs loaded with antisense oligonucleotides (ASOs) in a full 96-well plate within 3 hrs. ASO-loaded LNPs were formulated by an automated solvent-injection method using a robotic liquid handler, and assessed for particle size distribution, encapsulation efficiency, and stability with different formulation compositions and ASO loadings. Results indicated that the PEGylated lipid content significantly affected the particle size distribution, while the ionizable lipid / ASO charge ratio impacted the encapsulation efficiency of ASOs. Furthermore, results from our HTS approach correlated with those from the state-of-the-art scale-up method using a microfluidic formulator, therefore opening up a new avenue for robust formulation development and design of experiment methods, while reducing material usage by 10 folds, improving analytical outputs and accumulation of information by 100 folds.

Antitumor Activity of Lipid-DNA Aptamer Modified T Lymphocytes in Carcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease with no current effective therapeutics. One of the main reasons for the low efficacy of PDAC immunotherapy is the limited CD8+ T cell infiltration, without neo antigen present in PDAC. Aptamers represent single-stranded oligonucleotides which bind to specific targets with high specificity. We developed DNA conjugates and prepared diacyl phospholipid-aptamer XQ-2d which has potential for the targeted therapy and diagnosis of PDAC. In this study, flow cytometry and fluorescence microscopy were employed to assess whether the Lipo-XQ-2d probe could anchor on activated T cells to constitute ligands specifically recognizing PDAC PL45 cells. Flow cytometry was employed to determine cytotoxicity in activated T cells. Results showed that the Lipo-XQ-2d probe could be inserted into T cells, and was specifically bound to both T cells and PL45 cells. In addition, the Lipo-XQ-2d probe redirected T cells to kill PL45 cells in vitro and was not toxic to cells. In conclusion, lipid-DNA-aptamer-modified T-lymphocytes might effectively kill PDAC in vitro, supporting the clinical application of T cell adoptive immunotherapy.

Chelation-assisted assembly of multidentate colloidal nanoparticles into metal-organic nanoparticles.

We propose a chelation-assisted assembly of multidentate CNs into metal-organic nanoparticles (MONs). Multidentate CNs functionalized with coordination sites participate equally as organic linkers in MON construction, which is driven by chelation between metal ions and coordination sites. MONs assembled from Au nanoparticles display particle number- and size-dependent optical properties. In addition, the resulting CN-assembled MONs give evidence that assembly was dictated by the multidentate surface ligand rather than the size, shape or material of CNs. With this chelation-assisted strategy, it is possible to control the number of assembled CNs and build the connections between them.

Self-Assembled Aptamer-Grafted Hyperbranched Polymer Nanocarrier for Targeted and Photoresponsive Drug Delivery.

Photoresponsive materials are emerging as ideal carriers for precisely controlled drug delivery owing to their high spatiotemporal selectivity. However, drawbacks such as slow release kinetics, inherent toxicity, and lack of targeting ability hinder their translation into clinical use. We constructed a new DNA aptamer-grafted photoresponsive hyperbranched polymer, which can self-assemble into nanoparticles, thereby achieving biocompatibility and target specificity, as well as light-controllable release behavior. Upon UV-irradiation, rapid release induced by disassembly was observed for Nile Red-loaded nanoparticles. Further in vitro cell studies confirmed this delivery system's specific binding and internalization performance arising from the DNA aptamer corona. The DOX-loaded nanoassembly exhibited selective phototriggered cytotoxicity towards cancer cells, indicating its promising therapeutic effect as a smart drug delivery system.

ZrMOF nanoparticles as quenchers to conjugate DNA aptamers for target-induced bioimaging and photodynamic therapy.

Porphyrinic metal-organic framework (MOF) nanoparticles for photodynamic therapy solve the photosensitizer problems of poor solubility, self-quenching and aggregation. However, their low selectivity towards malignant tissues is an obstacle for bioimaging and a bottle-neck to cellular uptake for highly efficient photodynamic therapy of cancer. Here, ZrMOF nanoparticles as quenchers to conjugate DNA aptamers were developed for target-induced bioimaging and photodynamic therapy. A phosphate-terminal aptamer prepared by solid-phase DNA synthesis was anchored on the surface of ZrMOF nanoparticles through strong coordination between phosphate and zirconium. Based on π-π stacking-induced quenching of TAMRA by ZrMOF nanoparticles, target-induced imaging is achieved due to the structural change of the aptamer upon binding with the target. Aptamer-conjugated ZrMOF nanoparticles with target binding ability significantly enhanced the photodynamic therapy effect. Furthermore, phosphate-terminal aptamer conjugation method can be generalized to other types of MOF nanomaterials, such as UiO-66 and HfMOF nanoparticles, which can be potentially used in biochemistry.

Cross-Linked Aptamer-Lipid Micelles for Excellent Stability and Specificity in Target-Cell Recognition.

The specific binding ability of DNA-lipid micelles (DLMs) can be increased by the introduction of an aptamer. However, supramolecular micellar structures based on self-assemblies of amphiphilic DLMs are expected to demonstrate low stability when interacting with cell membranes under certain conditions, which could lead to a reduction in selectivity for targeting cancer cells. We herein report a straightforward cross-linking strategy that relies on a methacrylamide branch to link aptamer and lipid segments. By an efficient photoinduced polymerization process, covalently linked aptamer-lipid units help stabilize the micelle structure and enhance aptamer probe stability, further improving the targeting ability of the resulting nanoassembly. Besides the development of a facile cross-linking method, this study clarifies the relationship between aptamer-lipid concentration and the corresponding binding ability.