Mol* Volumes and Segmentations: visualization and interpretation of cell imaging data alongside macromolecular structure data and biological annotations.

Segmentation helps interpret imaging data in a biological context. With the development of powerful tools for automated segmentation, public repositories for imaging data have added support for sharing and visualizing segmentations, creating the need for interactive web-based visualization of 3D volume segmentations. To address the ongoing challenge of integrating and visualizing multimodal data, we developed Mol* Volumes and Segmentations (Mol*VS), which enables the interactive, web-based visualization of cellular imaging data supported by macromolecular data and biological annotations. Mol*VS is fully integrated into Mol* Viewer, which is already used for visualization by several public repositories. All EMDB and EMPIAR entries with segmentation datasets are accessible via Mol*VS, which supports the visualization of data from a wide range of electron and light microscopy experiments. Additionally, users can run a local instance of Mol*VS to visualize and share custom datasets in generic or application-specific formats including volumes in .ccp4, .mrc, and .map, and segmentations in EMDB-SFF .hff, Amira .am, iMod .mod, and Segger .seg. Mol*VS is open source and freely available at https://molstarvolseg.ncbr.muni.cz/.

MDsrv: visual sharing and analysis of molecular dynamics simulations.

Molecular dynamics simulation is a proven technique for computing and visualizing the time-resolved motion of macromolecules at atomic resolution. The MDsrv is a tool that streams MD trajectories and displays them interactively in web browsers without requiring advanced skills, facilitating interactive exploration and collaborative visual analysis. We have now enhanced the MDsrv to further simplify the upload and sharing of MD trajectories and improve their online viewing and analysis. With the new instance, the MDsrv simplifies the creation of sessions, which allows the exchange of MD trajectories with preset representations and perspectives. An important innovation is that the MDsrv can now access and visualize trajectories from remote datasets, which greatly expands its applicability and use, as the data no longer needs to be accessible on a local server. In addition, initial analyses such as sequence or structure alignments, distance measurements, or RMSD calculations have been implemented, which optionally support visual analysis. Finally, based on Mol*, MDsrv now provides faster and more efficient visualization of even large trajectories compared to its predecessor tool NGL.

Bringing Molecular Dynamics Simulation Data into View.

Molecular dynamics (MD) simulations monitor time-resolved motions of macromolecules. While visualization of MD trajectories allows an instant and intuitive understanding of dynamics and function, so far mainly static representations are provided in the published literature. Recent advances in browser technology may allow for the sharing of trajectories through interactive visualization on the web. We believe that providing intuitive and interactive visualization, along with related protocols and analysis data, promotes understanding, reliability, and reusability of MD simulations. Existing barriers for sharing MD simulations are discussed and emerging solutions are highlighted. We predict that interactive visualization of MD trajectories will quickly be adopted by researchers, research consortiums, journals, and funding agencies to gather and distribute results from MD simulations via the web.

Mol* Viewer: modern web app for 3D visualization and analysis of large biomolecular structures.

Large biomolecular structures are being determined experimentally on a daily basis using established techniques such as crystallography and electron microscopy. In addition, emerging integrative or hybrid methods (I/HM) are producing structural models of huge macromolecular machines and assemblies, sometimes containing 100s of millions of non-hydrogen atoms. The performance requirements for visualization and analysis tools delivering these data are increasing rapidly. Significant progress in developing online, web-native three-dimensional (3D) visualization tools was previously accomplished with the introduction of the LiteMol suite and NGL Viewers. Thereafter, Mol* development was jointly initiated by PDBe and RCSB PDB to combine and build on the strengths of LiteMol (developed by PDBe) and NGL (developed by RCSB PDB). The web-native Mol* Viewer enables 3D visualization and streaming of macromolecular coordinate and experimental data, together with capabilities for displaying structure quality, functional, or biological context annotations. High-performance graphics and data management allows users to simultaneously visualise up to hundreds of (superimposed) protein structures, stream molecular dynamics simulation trajectories, render cell-level models, or display huge I/HM structures. It is the primary 3D structure viewer used by PDBe and RCSB PDB. It can be easily integrated into third-party services. Mol* Viewer is open source and freely available at https://molstar.org/.

RCSB Protein Data Bank: powerful new tools for exploring 3D structures of biological macromolecules for basic and applied research and education in fundamental biology, biomedicine, biotechnology, bioengineering and energy sciences.

The Research Collaboratory for Structural Bioinformatics Protein Data Bank (RCSB PDB), the US data center for the global PDB archive and a founding member of the Worldwide Protein Data Bank partnership, serves tens of thousands of data depositors in the Americas and Oceania and makes 3D macromolecular structure data available at no charge and without restrictions to millions of RCSB.org users around the world, including >660 000 educators, students and members of the curious public using PDB101.RCSB.org. PDB data depositors include structural biologists using macromolecular crystallography, nuclear magnetic resonance spectroscopy, 3D electron microscopy and micro-electron diffraction. PDB data consumers accessing our web portals include researchers, educators and students studying fundamental biology, biomedicine, biotechnology, bioengineering and energy sciences. During the past 2 years, the research-focused RCSB PDB web portal (RCSB.org) has undergone a complete redesign, enabling improved searching with full Boolean operator logic and more facile access to PDB data integrated with >40 external biodata resources. New features and resources are described in detail using examples that showcase recently released structures of SARS-CoV-2 proteins and host cell proteins relevant to understanding and addressing the COVID-19 global pandemic.

Laparoscopic cholecystectomy during the COVID-19 pandemic in a tertiary care hospital in Germany: higher rates of acute and gangrenous cholecystitis in elderly patients.

BACKGROUND: The COVID-19 pandemic caused a global health crisis in 2020. This pandemic also had a negative impact on standard procedures in general surgery. Surgeons were challenged to find the best treatment plans for patients with acute cholecystitis. The aim of this study is to investigate the impact of the COVID-19 pandemic on the outcomes of laparoscopic cholecystectomies performed in a tertiary care hospital in Germany. PATIENTS AND METHODS: We examined perioperative outcomes of patients who underwent laparoscopic cholecystectomy during the pandemic from March 22, 2020 (first national lockdown in Germany) to December 31, 2020. We then compared these to perioperative outcomes from the same time frame of the previous year. RESULTS: A total of 182 patients who underwent laparoscopic cholecystectomy during the above-mentioned periods were enrolled. The pandemic group consisted of 100 and the control group of 82 patients. Subgroup analysis of elderly patients (> 65 years old) revealed significantly higher rates of acute [5 (17.9%) vs. 20 (58.8%); p = 0.001] and gangrenous cholecystitis [0 (0.0%) vs. 7 (20.6%); p = 0.013] in the "pandemic subgroup". Furthermore, significantly more early cholecystectomies were performed in this subgroup [5 (17.9%) vs. 20 (58.8%); p = 0.001]. There were no significant differences between the groups both in the overall and subgroup analysis regarding the operation time, intraoperative blood loss, length of hospitalization, morbidity and mortality. CONCLUSION: Elderly patients showed particularly higher rates of acute and gangrenous cholecystitis during the pandemic. Laparoscopic cholecystectomy can be performed safely in the COVID-19 era without negative impact on perioperative results. Therefore, we would assume that laparoscopic cholecystectomy can be recommended for any patient with acute cholecystitis, including the elderly.

Real-time structural motif searching in proteins using an inverted index strategy.

Biochemical and biological functions of proteins are the product of both the overall fold of the polypeptide chain, and, typically, structural motifs made up of smaller numbers of amino acids constituting a catalytic center or a binding site that may be remote from one another in amino acid sequence. Detection of such structural motifs can provide valuable insights into the function(s) of previously uncharacterized proteins. Technically, this remains an extremely challenging problem because of the size of the Protein Data Bank (PDB) archive. Existing methods depend on a clustering by sequence similarity and can be computationally slow. We have developed a new approach that uses an inverted index strategy capable of analyzing >170,000 PDB structures with unmatched speed. The efficiency of the inverted index method depends critically on identifying the small number of structures containing the query motif and ignoring most of the structures that are irrelevant. Our approach (implemented at motif.rcsb.org) enables real-time retrieval and superposition of structural motifs, either extracted from a reference structure or uploaded by the user. Herein, we describe the method and present five case studies that exemplify its efficacy and speed for analyzing 3D structures of both proteins and nucleic acids.

BinaryCIF and CIFTools-Lightweight, efficient and extensible macromolecular data management.

3D macromolecular structural data is growing ever more complex and plentiful in the wake of substantive advances in experimental and computational structure determination methods including macromolecular crystallography, cryo-electron microscopy, and integrative methods. Efficient means of working with 3D macromolecular structural data for archiving, analyses, and visualization are central to facilitating interoperability and reusability in compliance with the FAIR Principles. We address two challenges posed by growth in data size and complexity. First, data size is reduced by bespoke compression techniques. Second, complexity is managed through improved software tooling and fully leveraging available data dictionary schemas. To this end, we introduce BinaryCIF, a serialization of Crystallographic Information File (CIF) format files that maintains full compatibility to related data schemas, such as PDBx/mmCIF, while reducing file sizes by more than a factor of two versus gzip compressed CIF files. Moreover, for the largest structures, BinaryCIF provides even better compression-factor ten and four versus CIF files and gzipped CIF files, respectively. Herein, we describe CIFTools, a set of libraries in Java and TypeScript for generic and typed handling of CIF and BinaryCIF files. Together, BinaryCIF and CIFTools enable lightweight, efficient, and extensible handling of 3D macromolecular structural data.

Surgical Margin Mapping of Melanoma In Situ Using In Vivo Reflectance Confocal Microscopy Mosaics.

BACKGROUND: Melanoma in situ (MIS) can have poorly defined borders and subclinical extension that makes margin control challenging. Reflectance confocal microscopy (RCM) is a promising noninvasive technique that can be used to assess subclinical spread. OBJECTIVE: To optimize surgical margins of histology-proven MIS using RCM mosaics. MATERIALS AND METHODS: Prospective review of 22 patients with histology-proven MIS who underwent RCM margin mapping prior to staged excision, between August 1, 2018, and August 13, 2020, at the Department of Dermatology, University of New Mexico, School of Medicine. RESULTS: Twenty patients (91%) had tumor clearance on the first stage using a 3-mm surgical margin after confocal margin mapping. CONCLUSION: Reflectance confocal microscopy margin mapping using the mosaic device tends to clear MIS in one stage, and the use of the handheld device may improve the accuracy for difficult anatomic areas. Current Procedural Terminology codes for RCM do not reflect the time required and complexity of the procedure. Reflectance confocal microscopy margin mapping prior to excision has the potential to decrease the number of stages needed for melanoma removal, reduce treatment time, and cost.

RCSB Protein Data Bank: biological macromolecular structures enabling research and education in fundamental biology, biomedicine, biotechnology and energy.

The Research Collaboratory for Structural Bioinformatics Protein Data Bank (RCSB PDB, rcsb.org), the US data center for the global PDB archive, serves thousands of Data Depositors in the Americas and Oceania and makes 3D macromolecular structure data available at no charge and without usage restrictions to more than 1 million rcsb.org Users worldwide and 600 000 pdb101.rcsb.org education-focused Users around the globe. PDB Data Depositors include structural biologists using macromolecular crystallography, nuclear magnetic resonance spectroscopy and 3D electron microscopy. PDB Data Consumers include researchers, educators and students studying Fundamental Biology, Biomedicine, Biotechnology and Energy. Recent reorganization of RCSB PDB activities into four integrated, interdependent services is described in detail, together with tools and resources added over the past 2 years to RCSB PDB web portals in support of a 'Structural View of Biology.'