Patients with esophageal cancer often experience clinically relevant deterioration of quality of life (QOL) after esophagectomy owing to malnutrition, lack of physical exercise, and psychological symptoms. This study aimed to evaluate the feasibility, safety, and efficacy of a comprehensive intervention model using a mobile health system (CIMmH) in patients with esophageal cancer after esophagectomy. Twenty patients with esophageal cancer undergoing the modified McKeown surgical procedure were invited to join the CIMmH program with both online and offline components for 12 weeks. The participants were assessed before surgery and again at 1 and 3 months after esophagectomy. QOL, depressive symptoms, anxiety, stress, nutrition, and physical fitness were measured. Of the 20 patients, 16 (80%) completed the program. One month after esophagectomy, patients showed significant deterioration in overall QOL (P=.02), eating (P=.005), reflux (P=.04), and trouble with talking (P<.001). At the 3-month follow-upina. Chinese Clinical Trial Registry (ChiCTR-IPR-1800019900); http//www.chictr.org.cn/showprojen.aspx?proj=32811. Chinese Clinical Trial Registry (ChiCTR-IPR-1800019900); http//www.chictr.org.cn/showprojen.aspx?proj=32811. Performing physiotherapy exercises in front of a physiotherapist yields qualitative assessment notes and immediate feedback. However, practicing the exercises at home lacks feedback on how well patients are performing the prescribed tasks. The absence of proper feedback might result in patients performing the exercises incorrectly, which could worsen their condition. https://www.selleckchem.com/products/pnd-1186-vs-4718.html We present an approach to generate performance scores to enable tracking the progress by both the patient at home and the physiotherapist in the clinic. This study aims to propose the use of 2 machine learning algorithms, dynamic time warping (DTW) and hidden Markov model (HMM), to quantitatively assess the patient's performance with respect to a reference. Movement data were recorded using a motion sensor (Kinect V2), capable of detecting 25 joints in the human skeleton model, and were compared with those of a reference. A total of 16 participants were recruited to perform 4 different exercises shoulder abduction, hip abduction, lunge, andf a physiotherapy program to capture and report general performance, whereas DTW could be used later to focus on the details. The scores enable the patient to monitor their daily performance. They can also be reported back to the physiotherapist to track and assess patient progress, provide feedback, and adjust the exercise program if needed. To facilitate adherence to adaptive pain management behaviors after interdisciplinary multimodal pain treatment, we developed a mobile health app (AGRIPPA app) that contains two behavior regulation strategies. The aims of this project are (1) to test the effectiveness of the AGRIPPA app on pain disability; (2) to determine the cost-effectiveness; and (3) to explore the levels of engagement and usability of app users. We will perform a multicenter randomized controlled trial with two parallel groups. Within the 12-month inclusion period, we plan to recruit 158 adult patients with chronic pain during the initial stage of their interdisciplinary treatment program in one of the 6 participating centers. Participants will be randomly assigned to the standard treatment condition or to the enhanced treatment condition in which they will receive the AGRIPPA app. Patients will be monitored from the start of the treatment program until 12 months posttreatment. In our primary analysis, we will evaluate the difference over time of pain-related disability between the two conditions. Other outcome measures will include health-related quality of life, illness perceptions, pain self-efficacy, app system usage data, productivity loss, and health care expenses. The study was approved by the local Medical Research Ethics Committee in October 2019. As of March 20, 2020, we have recruited 88 patients. This study will be the first step in systematically evaluating the effectiveness and efficiency of the AGRIPPA app. After 3 years of development and feasibility testing, this formal evaluation will help determine to what extent the app will influence the maintenance of treatment gains over time. The outcomes of this trial will guide future decisions regarding uptake in clinical practice. Netherlands Trial Register NL8076; https//www.trialregister.nl/trial/8076. DERR1-10.2196/18632. DERR1-10.2196/18632.Genome replication is initiated from specific origin sites established by dynamic events. The Origin Recognition Complex (ORC) is necessary for orchestrating the initiation process by binding to origin DNA, recruiting CDC6, and assembling the MCM replicative helicase on DNA. Here we report five cryoEM structures of the human ORC (HsORC) that illustrate the native flexibility of the complex. The absence of ORC1 revealed a compact, stable complex of ORC2-5. Introduction of ORC1 opens the complex into several dynamic conformations. Two structures revealed dynamic movements of the ORC1 AAA+ and ORC2 winged-helix domains that likely impact DNA incorporation into the ORC core. Additional twist and pinch motions were observed in an open ORC conformation revealing a hinge at the ORC5·ORC3 interface that may facilitate ORC binding to DNA. Finally, a structure of ORC was determined with endogenous DNA bound in the core revealing important differences between human and yeast origin recognition.Specific protein-lipid interactions are critical for viral assembly. We present a molecular dynamics simulation study on the binding mechanism of the membrane targeting domain of HIV-1 Gag protein. The matrix (MA) domain drives Gag onto the plasma membrane through electrostatic interactions at its highly-basic-region (HBR), located near the myristoylated (Myr) N-terminus of the protein. Our study suggests Myr insertion is involved in the sorting of membrane lipids around the protein-binding site to prepare it for viral assembly. Our realistic membrane models confirm interactions with PIP2 and PS lipids are highly favored around the HBR and are strong enough to keep the protein bound even without Myr insertion. We characterized Myr insertion events from microsecond trajectories and examined the membrane response upon initial membrane targeting by MA. Insertion events only occur with one of the membrane models, showing a combination of surface charge and internal membrane structure modulate this process.