Citations

AbstractNanoparticles form long‐range micropatterns via self‐assembly or directed self‐assembly with superior mechanical, electrical, optical, magnetic, chemical, and other functional properties for broad applications, such as structural supports, thermal exchangers, optoelectronics, microelectronics, and robotics. The precisely defined particle assembly at the nanoscale with simultaneously scalable patterning at the microscale is indispensable for enabling functionality and improving the performance of devices. This article provides a comprehensive review of nanoparticle assembly formed primarily via the balance of forces at the nanoscale (e.g., van der Waals, colloidal, capillary, convection, and chemical forces) and nanoparticle‐template interactions (e.g., physical confinement, chemical functionalization, additive layer‐upon‐layer). The review commences with a general overview of nanoparticle self‐assembly, with the state‐of‐the‐art literature review and motivation. It subsequently reviews the recent progress in nanoparticle assembly without the presence of surface templates. Manufacturing techniques for surface template fabrication and their influence on nanoparticle assembly efficiency and effectiveness are then explored. The primary focus is the spatial organization and orientational preference of nanoparticles on non‐templated and pre‐templated surfaces in a controlled manner. Moreover, the article discusses broad applications of micropatterned surfaces, encompassing various fields. Finally, the review concludes with a summary of manufacturing methods, their limitations, and future trends in nanoparticle assembly.

Autophagy induction involves extensive molecular and membrane reorganization. Despite substantial progress, the mechanism underlying autophagy initiation remains poorly understood. Here, we used quantitative photoactivated localization microscopy with single-molecule sensitivity to analyze the nanoscopic distribution of endogenous ULK1, the kinase that triggers autophagy. Under amino acid starvation, ULK1 formed large clusters containing up to 161 molecules at the endoplasmic reticulum. Cross-correlation analysis revealed that ULK1 clusters engaging in autophagosome formation require 30 or more molecules. The ULK1 structures with more than the threshold number contained varying levels of Atg13, Atg14, Atg16, LC3B, GEC1, and WIPI2. We found that ULK1 activity is dispensable for the initial clustering of ULK1, but necessary for the subsequent expansion of the clusters, which involves interaction with Atg14, Atg16, and LC3B and relies on Vps34 activity. This quantitative analysis at the single-molecule level has provided unprecedented insights into the behavior of ULK1 during autophagy initiation.

Abstract Context The impact of insulin, particularly exogenous hyperinsulinemia, on insulin secretion in humans is debated. Objective We assessed the effects of exogenous hyperinsulinemia on insulin secretion and whether the response is altered in insulin resistance associated with obesity. Methods Insulin secretion rates (ISRs) during euglycemic hyperinsulinemic clamp studies (52 volunteers) were calculated using a model that employs plasma C-peptide concentrations. One study involved a 2-step insulin clamp and the other study was a single step insulin clamp. For both studies the goal was to achieve plasma glucose concentrations of 95 mg/dL during the clamp irrespective of fasting glucose concentrations. The percent change in ISR from fasting to the end of the insulin clamp interval was the main outcome. Linear regression and analysis of covariance were used to test for the effects of insulin on ISR and to test for group differences. Results ISR was greater in obese volunteers (P < .001) under fasting and hyperinsulinemic clamp conditions. The change in plasma glucose from baseline to the end of the insulin clamp interval was highly correlated with the change in ISR (r = 0.61, P < .001). From baseline to the end of the clamp we observed a 27% (SD 20) suppression of ISR. The participants who underwent a 2-step insulin clamp had greater suppression of ISR during the second step than the first step (P < .001). The proportional suppression of ISR during euglycemic hyperinsulinemia was not different between nonobese and obese groups (P = .19). Conclusion Hyperinsulinemia suppresses endogenous insulin secretion and the relative change in insulin secretion produced by exogenous insulin did not differ between nonobese and obese people.

Background: Arthrofibrosis (AF) after anterior cruciate ligament reconstruction (ACLR) remains a challenge. There is a paucity of data on arthroscopic interventions for AF after ACLR. Purpose: To (1) describe the patient, injury, and surgical characteristics and patient-reported outcomes (PROs) of those requiring an arthroscopic intervention for loss of motion after ACLR and (2) compare outcomes between patients undergoing an early intervention (within 3 months) versus those undergoing a late intervention (after 3 months). Study Design: Case series; Level of evidence, 4. Methods: Patients with a history of ACLR and a subsequent operative procedure for postoperative AF at a single institution between 2000 and 2018 were retrospectively identified. Arthroscopic interventions included lysis of adhesions, capsular release with or without manipulation under anesthesia, and excision of cyclops lesions. Patients were excluded if they had a knee dislocation or multiple-ligament injury, a periarticular fracture, or less than 2-year follow-up from the arthroscopic intervention. PROs including the Tegner activity score, visual analog scale pain score, and International Knee Documentation Committee score as well as knee range of motion (ROM) were recorded. Results: A total of 40 patients were included with a mean age of 27.2 years (range, 11.0-63.8 years) at surgery and a mean follow-up of 10.0 years (range, 2.9-20.7 years). The mean preoperative flexion and extension were 102° (range, 40°-150°) and 8° (range, 0°-25°), respectively. The mean postoperative flexion and extension were 131° (range, 110° to 150°) and 0° (range, –10° to 5°), respectively. After the arthroscopic intervention, the mean ROM improved from 94° (range, 40°-140°) preoperatively to 131° (range, 107°-152°) at final follow-up ( P < .001), and the visual analog scale pain score improved from 3.0 preoperatively to 1.2 postoperatively ( P = .001). Overall, 13 patients (32.5%) underwent an intervention within 3 months and 27 (67.5%) after 3 months. The early intervention group had a higher postoperative International Knee Documentation Committee score compared with the late intervention group (86.8 vs 71.7, respectively; P = .035). Conclusion: An arthroscopic intervention for AF after ACLR successfully improved knee ROM and pain. Patients who underwent either early or late surgery obtained satisfactory motion and function, although improved PROs were observed when the intervention occurred within 3 months of the primary procedure.

AbstractBackgroundKilo‐voltage cone‐beam computed tomography (CBCT) is a prevalent modality used for adaptive radiotherapy (ART) due to its compatibility with linear accelerators and ability to provide online imaging. However, the widely‐used Feldkamp‐Davis‐Kress (FDK) reconstruction algorithm has several limitations, including potential streak aliasing artifacts and elevated noise levels. Iterative reconstruction (IR) techniques, such as total variation (TV) minimization, dictionary‐based methods, and prior information‐based methods, have emerged as viable solutions to address these limitations and improve the quality and applicability of CBCT in ART.PurposeOne of the primary challenges in IR‐based techniques is finding the right balance between minimizing image noise and preserving image resolution. To overcome this challenge, we have developed a new reconstruction technique called high‐resolution CBCT (HRCBCT) that specifically focuses on improving image resolution while reducing noise levels.MethodsThe HRCBCT reconstruction technique builds upon the conventional IR approach, incorporating three components: the data fidelity term, the resolution preservation term, and the regularization term. The data fidelity term ensures alignment between reconstructed values and measured projection data, while the resolution preservation term exploits the high resolution of the initial Feldkamp‐Davis‐Kress (FDK) algorithm. The regularization term mitigates noise during the IR process. To enhance convergence and resolution at each iterative stage, we applied Iterative Filtered Backprojection (IFBP) to the data fidelity minimization process.ResultsWe evaluated the performance of the proposed HRCBCT algorithm using data from two physical phantoms and one head and neck patient. The HRCBCT algorithm outperformed all four different algorithms; FDK, Iterative Filtered Back Projection (IFBP), Compressed Sensing based Iterative Reconstruction (CSIR), and Prior Image Constrained Compressed Sensing (PICCS) methods in terms of resolution and noise reduction for all data sets. Line profiles across three line pairs of resolution revealed that the HRCBCT algorithm delivered the highest distinguishable line pairs compared to the other algorithms. Similarly, the Modulation Transfer Function (MTF) measurements, obtained from the tungsten wire insert on the CatPhan 600 physical phantom, showed a significant improvement with HRCBCT over traditional algorithms.ConclusionThe proposed HRCBCT algorithm offers a promising solution for enhancing CBCT image quality in adaptive radiotherapy settings. By addressing the challenges inherent in traditional IR methods, the algorithm delivers high‐definition CBCT images with improved resolution and reduced noise throughout each iterative step. Implementing the HR CBCT algorithm could significantly impact the accuracy of treatment planning during online adaptive therapy.

Across multiancestry groups, we analyzed Human Leukocyte Antigen (HLA) associations in over 176,000 individuals with Parkinson’s disease (PD) and Alzheimer’s disease (AD) versus controls. We demonstrate that the two diseases share the same protective association at the HLA locus. HLA-specific fine-mapping showed that hierarchical protective effects of HLA-DRB1 *04 subtypes best accounted for the association, strongest with HLA-DRB1 *04:04 and HLA-DRB1 *04:07, and intermediary with HLA-DRB1 *04:01 and HLA-DRB1 *04:03. The same signal was associated with decreased neurofibrillary tangles in postmortem brains and was associated with reduced tau levels in cerebrospinal fluid and to a lower extent with increased Aβ42. Protective HLA-DRB1 *04 subtypes strongly bound the aggregation-prone tau PHF6 sequence, however only when acetylated at a lysine (K311), a common posttranslational modification central to tau aggregation. An HLA-DRB1 *04-mediated adaptive immune response decreases PD and AD risks, potentially by acting against tau, offering the possibility of therapeutic avenues.

In this article, we present a flexible model for microbiome count data. We consider a quasi‐likelihood framework, in which we do not make any assumptions on the distribution of the microbiome count except that its variance is an unknown but smooth function of the mean. By comparing our model to the negative binomial generalized linear model (GLM) and Poisson GLM in simulation studies, we show that our flexible quasi‐likelihood method yields valid inferential results. Using a real microbiome study, we demonstrate the utility of our method by examining the relationship between adenomas and microbiota. We also provide an R package “fql” for the application of our method.

Background: Most people with coronavirus disease 2019 (COVID-19) experience resolution of symptoms within days to weeks following initial infection. In a subset of individuals, symptoms persist longer than 4 weeks, known as ‘Long COVID’. Many gastrointestinal (GI) symptoms persist as part of this syndrome; yet, an approach to treatment remains unclear. Prior studies have demonstrated the efficacy of complementary and alternative medicine (CAM) for the treatment of acute COVID-19 infections, but little data exist regarding the potential use of CAM in the treatment of Long COVID. Objectives: Identify CAM approaches useful in treating the GI symptoms of Long COVID. Design: A systematic review of studies reporting on the use of CAM for the treatment of GI symptoms of Long COVID was performed. Data Sources and Methods: Five electronic databases were searched from January 2019 to November 2022. Studies describing the use of CAM to treat GI symptoms of Long COVID were included and assessed by two independent reviewers. Studies not reporting on GI symptoms or using CAM were excluded. Studies chosen for final review underwent quality and bias assessment using predetermined criteria. The extracted data were synthesized utilizing a framework derived from the National Center of Complementary and Integrative Health categories. Results: The initial search yielded 396 articles. After applying the eligibility criteria, a total of four studies (three case reports and one case series) were included for final review. Two studies used nutritional supplements and two studies used traditional Chinese medicine. Reductions in nausea, loss of appetite, diarrhea, acid reflux, epigastric pain, and bloating were reported. Conclusion: This is the first systematic review to explore the role of CAM in treating GI manifestations of Long COVID. The review identified four studies, all reporting reductions in the GI symptoms of Long COVID. Despite the positive studies included in this review, the overall search yielded few results, all of which were non-experimental. As the post-infectious sequelae of COVID-19 become better recognized in the wake of the pandemic, higher-quality clinical studies are needed.