Evaluation of 30-day morbidity and mortality of laparoscopic cholecystectomy: a multicenter prospective observational Indian Association of Gastrointestinal Endoscopic Surgeons (IAGES) Study.

Background: Laparoscopic cholecystectomy (LC) is the standard of care for benign gallstone disease. There are no robust Indian data on the 30-day morbidity and mortality of this procedure. A prospective multicentre observational study was conducted by the Indian Association of Gastro-Intestinal Endo Surgeons (IAGES) to assess the 30-day morbidity and mortality of LC in India.

Coarse-Grained Simulation of Bottlebrush: From Single-Chain Properties to Self-Assembly.

Bottlebrush polymers consist of a linear backbone with densely grafted side chains. They are known to have a range of properties of interest, such as enhanced mechanical strength and rapid self-assembly into large domains, and have attracted attention as promising candidates for applications in photonics, lithography, energy storage, organic optoelectronics, and drug delivery. Here, we present a coarse-grained model of bottlebrush polymers that is able to reproduce their experimentally observed persistence lengths and chain conformations in the melt.

Satellite repeat RNA expression in epithelial ovarian cancer associates with a tumor-immunosuppressive phenotype.

Aberrant expression of viral-like repeat elements is a common feature of epithelial cancers, and the substantial diversity of repeat species provides a distinct view of the cancer transcriptome. Repeatome profiling across ovarian, pancreatic, and colorectal cell lines identifies distinct clustering independent of tissue origin that is seen with coding gene analysis. Deeper analysis of ovarian cancer cell lines demonstrated that human satellite II (HSATII) satellite repeat expression was highly associated with epithelial-mesenchymal transition (EMT) and anticorrelated with IFN-response genes indicative of a more aggressive phenotype.

Self-Aligned Assembly of a Poly(2-vinylpyridine)--Polystyrene--Poly(2-vinylpyridine) Triblock Copolymer on Graphene Nanoribbons.

Directed self-assembly (DSA) of block copolymers is one of the most promising patterning techniques for patterning sub-10 nm features. However, at such small feature sizes, it is becoming increasingly difficult to fabricate the guiding pattern for the DSA process, and it is necessary to explore alternative guiding methods for DSA to achieve long-range ordered alignment. Here, we report the self-aligned assembly of a triblock copolymer, poly(2-vinylpyridine)--polystyrene--poly(2-vinylpyridine) (P2VP--PS--P2VP) on neutral graphene nanoribbons with the gap consisting of a P2VP-preferential silicon oxide (SiO) substrate via solvent vapor annealing.

Mesoscale Simulations of Polymer Solution Self-Assembly: Selection of Model Parameters within an Implicit Solvent Approximation.

Coarse-grained modeling is an outcome of scientific endeavors to address the broad spectrum of time and length scales encountered in polymer systems. However, providing a faithful structural and dynamic characterization/description is challenging for several reasons, particularly in the selection of appropriate model parameters. By using a hybrid particle- and field-based approach with a generalized energy functional expressed in terms of density fields, we explore model parameter spaces over a broad range and map the relation between parameter values with experimentally measurable quantities, such as single-chain scaling exponent, chain density, and interfacial and surface tension.

Molecular Weight Dependent Morphological Transitions of Bottlebrush Block Copolymer Particles: Experiments and Simulations.

The molecular weights and chain rigidities of block copolymers can strongly influence their self-assembly behavior, particularly when the block copolymers are under confinement. We investigate the self-assembly of bottlebrush block copolymers (BBCPs) confined in evaporative emulsions with varying molecular weights. A series of symmetric BBCPs, where polystyrene (PS) and polylactide (PLA) side-chains are grafted onto a polynorbornene (PNB) backbone, are synthesized with varying degrees of polymerization of the PNB () ranging from 100 to 300.

Boundary-directed epitaxy of block copolymers.

Directed self-assembly of block copolymers (BCPs) enables nanofabrication at sub-10 nm dimensions, beyond the resolution of conventional lithography. However, directing the position, orientation, and long-range lateral order of BCP domains to produce technologically-useful patterns is a challenge. Here, we present a promising approach to direct assembly using spatial boundaries between planar, low-resolution regions on a surface with different composition.

Temporal and Spatial Heterogeneity of Host Response to SARS-CoV-2 Pulmonary Infection.

The relationship of SARS-CoV-2 lung infection and severity of pulmonary disease is not fully understood. We analyzed autopsy specimens from 24 patients who succumbed to SARS-CoV-2 infection using a combination of different RNA and protein analytical platforms to characterize inter- and intra- patient heterogeneity of pulmonary virus infection. There was a spectrum of high and low virus cases that was associated with duration of disease and activation of interferon pathway genes.

Epithelial to mesenchymal plasticity and differential response to therapies in pancreatic ductal adenocarcinoma.

Transcriptional profiling has defined pancreatic ductal adenocarcinoma (PDAC) into distinct subtypes with the majority being classical epithelial (E) or quasi-mesenchymal (QM). Despite clear differences in clinical behavior, growing evidence indicates these subtypes exist on a continuum with features of both subtypes present and suggestive of interconverting cell states. Here, we investigated the impact of different therapies being evaluated in PDAC on the phenotypic spectrum of the E/QM state.

Stromal Microenvironment Shapes the Intratumoral Architecture of Pancreatic Cancer.

Single-cell technologies have described heterogeneity across tissues, but the spatial distribution and forces that drive single-cell phenotypes have not been well defined. Combining single-cell RNA and protein analytics in studying the role of stromal cancer-associated fibroblasts (CAFs) in modulating heterogeneity in pancreatic cancer (pancreatic ductal adenocarcinoma [PDAC]) model systems, we have identified significant single-cell population shifts toward invasive epithelial-to-mesenchymal transition (EMT) and proliferative (PRO) phenotypes linked with mitogen-activated protein kinase (MAPK) and signal transducer and activator of transcription 3 (STAT3) signaling. Using high-content digital imaging of RNA in situ hybridization in 195 PDAC tumors, we quantified these EMT and PRO subpopulations in 319,626 individual cancer cells that can be classified within the context of distinct tumor gland "units.

Ewing's Sarcoma of the Cervical Spine.

In this article, we present the case of a 6-year-old female presented to the emergency department with progressive ascending motor weakness leading to cardiac arrest. The recent medical history included neck trauma 1 month prior to admission, 2 weeks of subjective fevers, and 1 day of urinary incontinence. After stabilization, and a review of the recent signs and symptoms, a magnetic resonance imaging of the neck revealed a posterior neck mass from C2 to T2.

Defect Annihilation Pathways in Directed Assembly of Lamellar Block Copolymer Thin Films.

Defects in highly ordered self-assembled block copolymers represent an important roadblock toward the adoption of these materials in a wide range of applications. This work examines the pathways for annihilation of defects in symmetric diblock copolymers in the context of directed assembly using patterned substrates. Past theoretical and computational studies of such systems have predicted minimum free energy pathways that are characteristic of an activated process.

SSAGES: Software Suite for Advanced General Ensemble Simulations.

Molecular simulation has emerged as an essential tool for modern-day research, but obtaining proper results and making reliable conclusions from simulations requires adequate sampling of the system under consideration. To this end, a variety of methods exist in the literature that can enhance sampling considerably, and increasingly sophisticated, effective algorithms continue to be developed at a rapid pace. Implementation of these techniques, however, can be challenging for experts and non-experts alike.

Solid-phase nucleation free-energy barriers in truncated cubes: interplay of localized orientational order and facet alignment.

The nucleation of ordered phases from the bulk isotropic phase of octahedron-like particles has been studied via Monte Carlo simulations and umbrella sampling. In particular, selected shapes that form ordered (plastic) phases with various symmetries (cubic and tetragonal) are chosen to unveil trends in the free-energy barrier heights (ΔG*'s) associated with disorder to order transitions. The shapes studied in this work have truncation parameter (s) values of 0.

Engineered nanointerfaces for microfluidic isolation and molecular profiling of tumor-specific extracellular vesicles.

Extracellular vesicles (EVs) carry RNA, DNA, proteins, and lipids. Specifically, tumor-derived EVs have the potential to be utilized as disease-specific biomarkers. However, a lack of methods to isolate tumor-specific EVs has limited their use in clinical settings.

Whole blood stabilization for the microfluidic isolation and molecular characterization of circulating tumor cells.

Precise rare-cell technologies require the blood to be processed immediately or be stabilized with fixatives. Such restrictions limit the translation of circulating tumor cell (CTC)-based liquid biopsy assays that provide accurate molecular data in guiding clinical decisions. Here we describe a method to preserve whole blood in its minimally altered state by combining hypothermic preservation with targeted strategies that counter cooling-induced platelet activation.

Hemobilia due to arteriobiliary fistula complicating ERCP for residual bile duct stone in a case of Mirizzi syndrome.

Hemobilia is a rare cause of upper gastrointestinal tract bleeding. Most cases are iatrogenic following medical interventions, most commonly liver biopsy and transhepatic cholangiography. We present a case of arteriobiliary fistula between the right hepatic artery and the common hepatic duct, in a case of Mirrizi syndrome, following endoscopic biliary stenting and presenting with hemobilia.

Prediction of potent shRNAs with a sequential classification algorithm.

We present SplashRNA, a sequential classifier to predict potent microRNA-based short hairpin RNAs (shRNAs). Trained on published and novel data sets, SplashRNA outperforms previous algorithms and reliably predicts the most efficient shRNAs for a given gene. Combined with an optimized miR-E backbone, >90% of high-scoring SplashRNA predictions trigger >85% protein knockdown when expressed from a single genomic integration.

Enhanced Isolation and Release of Circulating Tumor Cells Using Nanoparticle Binding and Ligand Exchange in a Microfluidic Chip.

The detection of rare circulating tumor cells (CTCs) in the blood of cancer patients has the potential to be a powerful and noninvasive method for examining metastasis, evaluating prognosis, assessing tumor sensitivity to drugs, and monitoring therapeutic outcomes. In this study, we have developed an efficient strategy to isolate CTCs from the blood of breast cancer patients using a microfluidic immune-affinity approach. Additionally, to gain further access to these rare cells for downstream characterization, our strategy allows for easy detachment of the captured CTCs from the substrate without compromising cell viability or the ability to employ next generation RNA sequencing for the identification of specific breast cancer genes.

BRD4 Connects Enhancer Remodeling to Senescence Immune Surveillance.

Unlabelled: Oncogene-induced senescence is a potent barrier to tumorigenesis that limits cellular expansion following certain oncogenic events. Senescent cells display a repressive chromatin configuration thought to stably silence proliferation-promoting genes while simultaneously activating an unusual form of immune surveillance involving a secretory program referred to as the senescence-associated secretory phenotype (SASP). Here, we demonstrate that senescence also involves a global remodeling of the enhancer landscape with recruitment of the chromatin reader BRD4 to newly activated super-enhancers adjacent to key SASP genes.

A tunable delivery platform to provide local chemotherapy for pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most devastating and painful cancers. It is often highly resistant to therapy owing to inherent chemoresistance and the desmoplastic response that creates a barrier of fibrous tissue preventing transport of chemotherapeutics into the tumor. The growth of the tumor in pancreatic cancer often leads to invasion of other organs and partial or complete biliary obstruction, inducing intense pain for patients and necessitating tumor resection or repeated stenting.

The Functional Human C-Terminome.

All translated proteins end with a carboxylic acid commonly called the C-terminus. Many short functional sequences (minimotifs) are located on or immediately proximal to the C-terminus. However, information about the function of protein C-termini has not been consolidated into a single source.

Simultaneous estimation of free energies and rates using forward flux sampling and mean first passage times.

In this work, a method is proposed to simultaneously compute the transition rate constant and the free energy profile of a rare event along an order parameter connecting two well-defined regions of phase space. The method employs a forward flux sampling technique in combination with a mean first passage time approach to estimate the steady state probability and mean first passage times. These quantities are fitted to a Markovian model that allows the estimation of the free energy along the chosen order parameter.