Early Diagnosis and Treatment of Cardiac Amyloidosis by Screening Biopsy During Trigger Finger Release.

Patients undergoing trigger release surgery are known to be at increased risk of amyloidosis and heart failure, and therefore, amyloidosis screening during trigger release surgery may facilitate early diagnosis and treatment of cardiac amyloidosis. However, the reported prevalence of amyloid on biopsies taken during trigger release surgery has varied widely, and no biopsy-positive patients in prior studies have been diagnosed with occult cardiac amyloidosis or started on disease-modifying therapy. We review the existing literature on this topic and present a case of a patient with cardiac amyloidosis diagnosed from a biopsy taken during trigger release surgery and subsequently started on disease-modifying therapy.

Musculoskeletal Tumor Society Member Survey: Intra-Operative Peripheral Margins in Soft Tissue Sarcoma.

Background And Objectives: Routine intraoperative peripheral margin sampling is often employed by musculoskeletal surgical oncologists. Several recommendations exist regarding this practice pattern. It is unknown what the practice patterns of Musculoskeletal Tumor Society (MSTS) members are.

Intraoperative Peripheral Frozen Margin Assessment in Soft Tissue Sarcoma.

Background/objectives: Intraoperative peripheral margin sampling in soft tissue sarcoma (STS) is a routine practice among musculoskeletal oncologists. Practice patterns are variable, and evidence to support it is lacking. Rates of peripheral margin sampling at our institution were analyzed in addition to its clinical utility and cost-effectiveness.

RedLionfish - fast Richardson-Lucy Deconvolution package for efficient point spread function suppression in volumetric data.

The experimental limitations with optics observed in many microscopy and astronomy instruments result in detrimental effects for the imaging of objects. This can be generally described mathematically as a convolution of the real object image with the point spread function that characterizes the optical system. The popular Richardson-Lucy (RL) deconvolution algorithm is widely used for the inverse process of restoring the data without these optical aberrations, often a critical step in data processing of experimental data.

Genetic Screen in a Preclinical Model of Sarcoma Development Defines Drivers and Therapeutic Vulnerabilities.

Purpose: High-grade complex karyotype sarcomas are a heterogeneous group of tumors with a uniformly poor prognosis. Within complex karyotype sarcomas, there are innumerable genetic changes but identifying those that are clinically relevant has been challenging.

Experimental Design: To address this, we utilized a pooled genetic screening approach, informed by The Cancer Genome Atlas (TCGA) data, to identify key drivers and modifiers of sarcoma development that were validated in vivo.

Neural mechanisms responsible for vagus nerve stimulation-dependent enhancement of somatosensory recovery.

Impairments in somatosensory function are a common and often debilitating consequence of neurological injury, with few effective interventions. Building on success in rehabilitation for motor dysfunction, the delivery of vagus nerve stimulation (VNS) combined with tactile rehabilitation has emerged as a potential approach to enhance recovery of somatosensation. In order to maximize the effectiveness of VNS therapy and promote translation to clinical implementation, we sought to optimize the stimulation paradigm and identify neural mechanisms that underlie VNS-dependent recovery.

Wearable high-density EMG sleeve for complex hand gesture classification and continuous joint angle estimation.

High-density electromyography (HD-EMG) can provide a natural interface to enhance human-computer interaction (HCI). This study aims to demonstrate the capability of a novel HD-EMG forearm sleeve equipped with up to 150 electrodes to capture high-resolution muscle activity, decode complex hand gestures, and estimate continuous hand position via joint angle predictions. Ten able-bodied participants performed 37 hand movements and grasps while EMG was recorded using the HD-EMG sleeve.

Osteochondroma-like parosteal osteosarcoma: A case highlighting diagnostic challenge and surgical advances.

Parosteal osteosarcomas are uncommon malignant bone tumors that arise from the bone surface. Their heterogenous components can present challenges in diagnosis. We present a case of a rare variant of this tumor known as an osteochondroma-like parosteal osteosarcoma, which was initially misdiagnosed as a cartilaginous tumor on core needle biopsy.

Identifying alterations in hand movement coordination from chronic stroke survivors using a wearable high-density EMG sleeve.

Non-invasive, high-density electromyography (HD-EMG) has emerged as a useful tool to collect a range of neurophysiological motor information. Recent studies have demonstrated changes in EMG features that occur after stroke, which correlate with functional ability, highlighting their potential use as biomarkers. However, previous studies have largely explored these EMG features in isolation with individual electrodes to assess gross movements, limiting their potential clinical utility.

Ot2Rec: A semi-automatic, extensible, multi-software tomographic reconstruction workflow.

Electron cryo-tomography is an imaging technique for probing 3D structures with at the nanometer scale. This technique has been used extensively in the biomedical field to study the complex structures of proteins and other macromolecules. With the advancement in technology, microscopes are currently capable of producing images amounting to terabytes of data per day, posing great challenges for scientists as the speed of processing of the images cannot keep up with the ever-higher throughput of the microscopes.

Okapi-EM: A napari plugin for processing and analyzing cryogenic serial focused ion beam/scanning electron microscopy images.

An emergent volume electron microscopy technique called cryogenic serial plasma focused ion beam milling scanning electron microscopy (pFIB/SEM) can decipher complex biological structures by building a three-dimensional picture of biological samples at mesoscale resolution. This is achieved by collecting consecutive SEM images after successive rounds of FIB milling that expose a new surface after each milling step. Due to instrumental limitations, some image processing is necessary before 3D visualization and analysis of the data is possible.

Correlative cryo-soft X-ray tomography and cryo-structured illumination microscopy reveal changes to lysosomes in amyloid-β-treated neurons.

Protein misfolding is common to neurodegenerative diseases (NDs) including Alzheimer's disease (AD), which is partly characterized by the self-assembly and accumulation of amyloid-beta in the brain. Lysosomes are a critical component of the proteostasis network required to degrade and recycle material from outside and within the cell and impaired proteostatic mechanisms have been implicated in NDs. We have previously established that toxic amyloid-beta oligomers are endocytosed, accumulate in lysosomes, and disrupt the endo-lysosomal system in neurons.

Effect of ALDH1A1 and CD44 on Survival and Disease Recurrence in Patients With Osteosarcoma.

Purpose: Emerging evidence suggests that osteosarcoma stem cells (OSCs) may be responsible for tumor initiation propagation, recurrence, and resistance to therapy. We set out to evaluate the relationship between the abundance of ALDH1A1 and CD44-positive cells in biopsy and resection samples on disease recurrence and overall survival.

Methods: A retrospective review of 20 patients, including biopsy and resection samples, was performed at a comprehensive cancer center.

Neural Mechanisms Responsible for Vagus Nerve Stimulation-Dependent Enhancement of Somatosensory Recovery.

Impairments in somatosensory function are a common and often debilitating consequence of neurological injury, with few effective interventions. Building on success in rehabilitation for motor dysfunction, the delivery of vagus nerve stimulation (VNS) combined with tactile rehabilitation has emerged as a potential approach to enhance recovery of somatosensation. In order to maximize the effectiveness of VNS therapy and promote translation to clinical implementation, we sought to optimize the stimulation paradigm and identify neural mechanisms that underlie VNS-dependent recovery.

Decoding hand and wrist movement intention from chronic stroke survivors with hemiparesis using a user-friendly, wearable EMG-based neural interface.

Objective: Seventy-five percent of stroke survivors, caregivers, and health care professionals (HCP) believe current therapy practices are insufficient, specifically calling out the upper extremity as an area where innovation is needed to develop highly usable prosthetics/orthotics for the stroke population. A promising method for controlling upper extremity technologies is to infer movement intention non-invasively from surface electromyography (EMG). However, existing technologies are often limited to research settings and struggle to meet user needs.

Characterization of natural killer and cytotoxic T-cell immune infiltrates in pancreatic ductal adenocarcinoma.

Background And Objectives: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer with poor response to systemic therapies, including immunotherapy. Given the immunotherapeutic potential of natural killer (NK) cells, we evaluated intratumoral NK cell infiltrates along with cytotoxic T cells in PDAC to determine their association with patient outcomes.

Methods: We analyzed tumors from 93 PDAC patients treated from 2012 to 2020.

Structural basis of substrate progression through the bacterial chaperonin cycle.

The bacterial chaperonin GroEL-GroES promotes protein folding through ATP-regulated cycles of substrate protein binding, encapsulation, and release. Here, we have used cryoEM to determine structures of GroEL, GroEL-ADP·BeF, and GroEL-ADP·AlF-GroES all complexed with the model substrate Rubisco. Our structures provide a series of snapshots that show how the conformation and interactions of non-native Rubisco change as it proceeds through the GroEL-GroES reaction cycle.

Label-Free Virtual HER2 Immunohistochemical Staining of Breast Tissue using Deep Learning.

The immunohistochemical (IHC) staining of the human epidermal growth factor receptor 2 (HER2) biomarker is widely practiced in breast tissue analysis, preclinical studies, and diagnostic decisions, guiding cancer treatment and investigation of pathogenesis. HER2 staining demands laborious tissue treatment and chemical processing performed by a histotechnologist, which typically takes one day to prepare in a laboratory, increasing analysis time and associated costs. Here, we describe a deep learning-based virtual HER2 IHC staining method using a conditional generative adversarial network that is trained to rapidly transform autofluorescence microscopic images of unlabeled/label-free breast tissue sections into bright-field equivalent microscopic images, matching the standard HER2 IHC staining that is chemically performed on the same tissue sections.

Intratumoral NKp46 natural killer cells are spatially distanced from T and MHC-I cells with prognostic implications in soft tissue sarcoma.

Introduction: Soft tissue sarcomas (STS) are rare, heterogenous malignancies with an unmet need for novel immunotherapies. Tumor infiltrating lymphocytes (TILs) have been linked with favorable outcomes in STS patients, though the contribution of natural killer (NK) cells and spatial relationships of TILs with MHC-I expressing cells lacks detailed characterization.

Experimental Design: Using archived and prospectively collected specimens, we evaluated intratumoral NK cells by immunohistochemistry (IHC), flow cytometry, and immunofluorescence (IF).

Langerhans cell histiocytosis with aneurysmal bone cyst-like changes: a case-based literature review.

Background: Langerhans cell histiocytosis (LCH) is a neoplastic transformation of myeloid precursors that commonly presents as an osteolytic lesion of the long or flat bones in children. Aneurysmal bone cysts (ABC) are benign neoplasms that frequently affect the metaphysis of long bones and the spine, often revealing a rapidly expansile lesion with fluid-fluid levels. LCH with secondary ABC-like changes is a rare condition that has only been reported five times, with two presentations in the cranium.

A protocol for cryogenic volumetric imaging using serial plasma FIB/SEM.

Cryogenic volumetric imaging using serial plasma focused ion beam scanning electron microscopy (serial pFIB/SEM) is a new and exciting correlative volume electron microscopy (vEM) technique. It enables visualization of un-stained, cryogenically immobilized cells and tissues with ∼20-50nm resolution and a field of view of ∼10-30μm resulting in near-native state imaging and the possibility of microscale, mesoscale and nanoscale correlative imaging. We have written a detailed protocol for optimization of FIB and SEM parameters to reduce imaging artefacts and enable downstream computational processing and analysis.

Online citizen science with the Zooniverse for analysis of biological volumetric data.

Public participation in research, also known as citizen science, is being increasingly adopted for the analysis of biological volumetric data. Researchers working in this domain are applying online citizen science as a scalable distributed data analysis approach, with recent research demonstrating that non-experts can productively contribute to tasks such as the segmentation of organelles in volume electron microscopy data. This, alongside the growing challenge to rapidly process the large amounts of biological volumetric data now routinely produced, means there is increasing interest within the research community to apply online citizen science for the analysis of data in this context.