Mature chromatin packing domains persist after RAD21 depletion in 3D.

Understanding chromatin organization requires integrating measurements of genome connectivity and physical structure. It is well established that cohesin is essential for TAD and loop connectivity features in Hi-C, but the corresponding change in physical structure has not been studied using electron microscopy. Pairing chromatin scanning transmission electron tomography with multiomic analysis and single-molecule localization microscopy, we study the role of cohesin in regulating the conformationally defined chromatin nanoscopic packing domains.

Chromatin conformation, gene transcription, and nucleosome remodeling as an emergent system.

In single cells, variably sized nanoscale chromatin structures are observed, but it is unknown whether these form a cohesive framework that regulates RNA transcription. Here, we demonstrate that the human genome is an emergent, self-assembling, reinforcement learning system. Conformationally defined heterogeneous, nanoscopic packing domains form by the interplay of transcription, nucleosome remodeling, and loop extrusion.

Leveraging chromatin packing domains to target chemoevasion .

Cancer cells exhibit a remarkable resilience to cytotoxic stress, often adapting through transcriptional changes linked to alterations in chromatin structure. In several types of cancer, these adaptations involve epigenetic modifications and restructuring of topologically associating domains (TADs). However, the underlying principles by which chromatin architecture facilitates such adaptability across different cancers remain poorly understood.

Local volume concentration, packing domains, and scaling properties of chromatin.

We propose the Self Returning Excluded Volume (SR-EV) model for the structure of chromatin based on stochastic rules and physical interactions. The SR-EV generate conformationally defined domains observed by single-cell imaging techniques. From nucleosome to chromosome scales, the model captures the overall chromatin organization as a corrugated system, with dense and dilute regions alternating in a manner that resembles the mixing of two disordered bi-continuous phases.

Three-color single-molecule localization microscopy in chromatin.

Super-resolution microscopy has revolutionized our ability to visualize structures below the diffraction limit of conventional optical microscopy and is particularly useful for investigating complex biological targets like chromatin. Chromatin exhibits a hierarchical organization with structural compartments and domains at different length scales, from nanometers to micrometers. Single molecule localization microscopy (SMLM) methods, such as STORM, are essential for studying chromatin at the supra-nucleosome level due to their ability to target epigenetic marks that determine chromatin organization.

Active transcription and epigenetic reactions synergistically regulate meso-scale genomic organization.

In interphase nuclei, chromatin forms dense domains of characteristic sizes, but the influence of transcription and histone modifications on domain size is not understood. We present a theoretical model exploring this relationship, considering chromatin-chromatin interactions, histone modifications, and chromatin extrusion. We predict that the size of heterochromatic domains is governed by a balance among the diffusive flux of methylated histones sustaining them and the acetylation reactions in the domains and the process of loop extrusion via supercoiling by RNAPII at their periphery, which contributes to size reduction.

Local Volume Concentration, Packing Domains and Scaling Properties of Chromatin.

We propose the Self Returning Excluded Volume (SR-EV) model for the structure of chromatin based on stochastic rules and physical interactions. The SR-EV generate conformationally-defined domains observed by single cell imaging techniques. From nucleosome to chromosome scales, the model captures the overall chromatin organization as a corrugated system, with dense and dilute regions alternating in a manner that resembles the mixing of two disordered bi-continuous phases.

Local Volume Concentration, Packing Domains and Scaling Properties of Chromatin.

We propose the Self Returning Excluded Volume (SR-EV) model for the structure of chromatin based on stochastic rules and physical interactions that is able to capture the observed behavior across imaging and sequencing based measures of chromatin organization. The SR-EV model takes the return rules of the Self Returning Random Walk, incorporates excluded volume interactions, chain connectivity and expands the length scales range from 10 nm to over 1 micron. The model is computationally fast and we created thousands of configurations that we grouped in twelve different ensembles according to the two main parameters of the model.

Efficacy, safety, and correlative biomarkers of bintrafusp alfa in recurrent or metastatic nasopharyngeal cancer patients: a phase II clinical trial.

Background: The strategy of dual blockade of TGF-β and PD-L1 pathways has not been previously tested in platinum-refractory recurrent or metastatic nasopharyngeal cancer (R/M NPC) patients. This study aimed to evaluate the safety and efficacy of bintrafusp alfa in refractory R/M NPC patients.

Methods: In this single-arm, single-centre phase II clinical trial, 38 histologically confirmed R/M NPC patients were enrolled and administered with bintrafusp alfa every 2 weeks.

Denoising Autoencoder Trained on Simulation-Derived Structures for Noise Reduction in Chromatin Scanning Transmission Electron Microscopy.

Scanning transmission electron microscopy tomography with ChromEM staining (ChromSTEM), has allowed for the three-dimensional study of genome organization. By leveraging convolutional neural networks and molecular dynamics simulations, we have developed a denoising autoencoder (DAE) capable of postprocessing experimental ChromSTEM images to provide nucleosome-level resolution. Our DAE is trained on synthetic images generated from simulations of the chromatin fiber using the 1-cylinder per nucleosome (1CPN) model of chromatin.

Analysis of three-dimensional chromatin packing domains by chromatin scanning transmission electron microscopy (ChromSTEM).

Chromatin organization over multiple length scales plays a critical role in the regulation of transcription. Deciphering the interplay of these processes requires high-resolution, three-dimensional, quantitative imaging of chromatin structure in vitro. Herein, we introduce ChromSTEM, a method that utilizes high-angle annular dark-field imaging and tomography in scanning transmission electron microscopy combined with DNA-specific staining for electron microscopy.

Supraligamentous Approach of Lateral Release in Endoscopic Lateral Soft Tissue Procedure.

Many surgical methods are available for hallux valgus, but consensus regarding the best management has yet to be established. Minimally invasive techniques are gaining popularity with the potential advantages of better cosmetic outcome, less postoperative pain, and decreasing recovery time because surgical exposure and deep soft tissue dissection are less extensive and possibly gentler. Recently, techniques of the endoscopic distal soft tissue procedure have been reported, in which an endoscopic approach of the classic distal soft tissue procedure is described.

Endoscopic Posterior Ankle Decompression and Release After Total Ankle Arthroplasty.

Accurate positioning of the total ankle arthroplasty implant components with the absence of any hindfoot deformity does not preclude the development of bony impingement. In cases of ankle stiffness after total ankle arthroplasty, the usual limitation is in dorsiflexion. If triceps surae contracture is excluded or persistent restriction remains in ankle dorsiflexion after gastrocnemius recession or tendo-Achilles lengthening, posterior ankle capsulectomy, debridement of posterior ankle gutter, and release of the deep posterior deltoid ligament and the posterior talofibular ligament are indicated.

COVID-19 vaccine acceptance and hesitancy among ethnic minorities in Hong Kong.

Ethnic minorities account for 8% of the Hong Kong population, most are Filipino and Indonesian domestic helpers taking care of children and the elderly. To understand the COVID-19 vaccination rates and factors associated with vaccine acceptance of ethnic minorities, we performed a cross-sectional questionnaire study recruiting Hong Kong ethnic minorities aged ≥18 years between 1 July and 18 July 2021 in public areas. Demographics, knowledge about COVID-19, vaccination status, intention and reasons to receive the vaccine, and planning to be re-vaccinated were analyzed.

Mobility, prosthesis use and health-related quality of life of bilateral lower limb amputees from the 2008 Sichuan earthquake.

Background:: The 2008 Sichuan Earthquake resulted in many amputees, yet due to the rare incidence, few studies have explored the rehabilitation outcomes and quality of life of bilateral lower limb amputees after major natural disasters.

Objectives:: To evaluate rehabilitation outcomes of 17 young and adult bilateral lower limb amputees under the StandTall rehabilitation programme and to identify factors associated with successful functional recovery of bilateral amputees after large-scale disasters.

Study Design:: Cross-sectional study.

Prophylaxis of radiation-induced nausea and vomiting: a systematic review and meta-analysis of randomized controlled trials.

Background: The aim of this article was to systematically review the efficacy and safety of various antiemetics in prophylaxis of radiation-induced nausea and vomiting (RINV).

Methods: A literature search of Ovid MEDLINE, EMBASE and Cochrane CENTRAL was performed to identify randomized controlled trials (RCTs) that evaluated the efficacy of prophylaxis for RINV in patients receiving radiotherapy to abdomen/pelvis, including total body irradiation (TBI). Primary endpoints were complete control of nausea and complete control of vomiting during acute and delayed phases.

Whole-exome sequencing identifies multiple loss-of-function mutations of NF-κB pathway regulators in nasopharyngeal carcinoma.

Nasopharyngeal carcinoma (NPC) is an epithelial malignancy with a unique geographical distribution. The genomic abnormalities leading to NPC pathogenesis remain unclear. In total, 135 NPC tumors were examined to characterize the mutational landscape using whole-exome sequencing and targeted resequencing.