Objective: To maximize local tumor control, stabilize affected bones, and preserve or replace joints with minimal interventional burden, thereby enhancing quality of life for empowered living.
Indications: Suitable for patients with bone metastases, particularly those with severe pain and/or fractures and appropriate life expectancy.
Contraindications: In primary bone tumors, refer to the sarcoma surgery team for evaluation of wide resection.
Somatic mosaicism is an important cause of disease, but mosaic and somatic variants are often challenging to detect because they exist in only a fraction of cells. To address the need for benchmarking subclonal variants in normal cell populations, we developed a benchmark containing mosaic variants in the Genome in a Bottle Consortium (GIAB) HG002 reference material DNA from a large batch of a normal lymphoblastoid cell line. First, we used a somatic variant caller with high coverage (300x) Illumina whole genome sequencing data from the Ashkenazi Jewish trio to detect variants in HG002 not detected in at least 5% of cells from the combined parental data.
View Article and Find Full Text PDFBackground: Large language models (LLMs), such as ChatGPT, excel at interpreting unstructured data from public sources, yet are limited when responding to queries on private repositories, such as electronic health records (EHRs). We hypothesized that prompt engineering could enhance the accuracy of LLMs for interpreting EHR data without requiring domain knowledge, thus expanding their utility for patients and personalized diagnostics.
Methods: We designed and systematically tested prompt engineering techniques to improve the ability of LLMs to interpret EHRs for nuanced diagnostic questions, referenced to a panel of medical experts.
Background: Fulminant idiopathic intracranial hypertension (IIH) is characterized by headache, rapid decrease of vision and elevated CSF-opening pressure.
Objective: To delineate a subgroup of MOGAD mimicking fulminant IIH.
Methods: In this case series children with MOGAD with vision loss, optic disc swelling and elevated CSF opening pressure, initially diagnosed with fulminant IIH, were included.
Excited-state intramolecular proton transfer (ESIPT)-associated dual-state emissive aliphatic dual-light emitting conducting polymers (DLECPs) having oxidation-reduction capacities are prepared polymerizing 2-acrylamido-2-methylpropane-1-sulfonic acid, methacrylic acid, and 2-methyl-3-(N-(2-methyl-1-sulfopropan-2-yl)acrylamido)propanoic acid monomers. Of as-synthesized DLECPs, nuclear magnetic resonance (NMR) and Fourier transform infrared (FTIR) spectroscopies, fluorescent enhancements (I/I), and computational investigation indicate intriguing photophysical features in DLECP3 (optimum composition). In DLECP3, ─CONH─, ─CON<, and ─COOH subluminophores are recognized by density-functional theory (DFT)/time-dependent-DFT calculations and experimental investigations.
View Article and Find Full Text PDFHerein, natural-synthetic hybrid dual-state luminescent conducting polymers (DLCPs/DLCP1-DLCP8) possessing significant optoelectrochemical properties are strategically developed by the polymerization of prop-2-enamide, cis-butenedioic acid, 2-acrylamido-2-methylpropane-1-sulfonic acid, and in situ-generated 2-(3-acrylamidopropanamido)-2-methylpropane-1-sulfonic acid alongside the grafting of gum tragacanth. The spectroscopic data of aliphatic DLCPs affirm DLCP7 as the most stable supramolecular assembly endowing optoelectronic properties. Computational calculations identified -C(═O)NH-, -C(═O)OH, -OH, and -SOH as subluminophores.
View Article and Find Full Text PDFInitially, four synthetic fluorescent polymers (SFPs) are synthesized from α-methacrylic acid and methanolacrylamide monomers carrying -C(=O)OH and -C(=O)NH subfluorophores, respectively. Among SFPs, ∼1:1 incorporation of subfluorophores in the optimum SFP3 is explored by spectroscopic analyses. Subsequently, chitosan is incorporated in SFP3 to produce five semi-synthetic fluorescent polymers (SSFPs).
View Article and Find Full Text PDFThe ClSS radical is one of the members of the XSS, XSO and XOO (X = H, F, Cl) radicals. It was studied by Fujitake using millimeter- and sub-millimeter wave spectroscopy, where no hyperfine structure was resolved. As the last piece of this series of radicals, it is important to determine the fine and hyperfine constants of the ClSS radical precisely using FTMW spectroscopy.
View Article and Find Full Text PDFBackground: Anterior instability of the sternoclavicular joint (SCJ) is a rare but potentially devastating pathological condition, particularly when it occurs in young or active patients. SCJ reconstruction using hamstring tendon autograft is a commonly used treatment option, yet to date results are limited to small case series. Studies on baseline, preoperative factors and their association with postoperative outcome are limited.
View Article and Find Full Text PDFWe present a TALEN-based workflow to generate and maintain dual-edited (IL-15/TGFβR2) iPSCs that produce enhanced iPSC-derived natural killer (iNK) cells for cancer immunotherapy. It involves using a cell lineage promoter for knocking in (KI) gene(s) to minimize the potential effects of expression of any exogenous genes on iPSCs. As a proof-of-principle, we KI IL-15 under the endogenous B2M promoter and show that it results in high expression of the sIL-15 in iNK cells but minimal expression in iPSCs.
View Article and Find Full Text PDFIntroduction: This paper presents a comprehensive investigation into the current and emerging solutions, policies, and guidance employed by various agencies to mitigate wrong-way driving (WWD) activities in the United States. The study utilized a two-pronged approach, involving an online survey and follow-up phone interviews with respondents from state transportation agencies, tollway authorities, and law enforcement.
Methods: The initial step involved conducting an online survey to gather general insights about the existing strategies and practices used to combat WWD.
Somatic variant detection is an integral part of cancer genomics analysis. While most methods have focused on short-read sequencing, long-read technologies now offer potential advantages in terms of repeat mapping and variant phasing. We present DeepSomatic, a deep learning method for detecting somatic SNVs and insertions and deletions (indels) from both short-read and long-read data, with modes for whole-genome and exome sequencing, and able to run on tumor-normal, tumor-only, and with FFPE-prepared samples.
View Article and Find Full Text PDFExtracellular vesicles (EVs) are present in blood at much lower concentrations (5-6 orders of magnitude) compared to lipoprotein particles (LP). Because LP and EV overlap in size and density, isolating high-purity EVs is a significant challenge. While the current two-step sequential EV isolation process using size-expression chromatography (SEC) followed by a density gradient (DG) achieves high purity, the time-consuming ultracentrifugation (UC) step in DG hinders workflow efficiency.
View Article and Find Full Text PDFCPT Pharmacometrics Syst Pharmacol
September 2024
Mavacamten is a selective, allosteric, reversible cardiac myosin inhibitor that has been developed for the treatment of adults with symptomatic obstructive hypertrophic cardiomyopathy (HCM). A population pharmacokinetic (PopPK) model was developed to characterize mavacamten pharmacokinetics (PK) and the variation in mavacamten exposure associated with intrinsic and extrinsic factors. Data from 12 clinical studies (phases 1, 2, and 3) were used.
View Article and Find Full Text PDFBackground: Cardiocerebral infarction (CCI), which is concomitant with acute myocardial infarction (AMI) and acute ischemic stroke (AIS), is a rare but severe presentation. However, there are few data on CCI, and the treatment options are uncertain. We investigated the characteristics and outcomes of CCI compared with AMI or AIS alone.
View Article and Find Full Text PDFLong-read sequencing technology has enabled variant detection in difficult-to-map regions of the genome and enabled rapid genetic diagnosis in clinical settings. Rapidly evolving third-generation sequencing platforms like Pacific Biosciences (PacBio) and Oxford Nanopore Technologies (ONT) are introducing newer platforms and data types. It has been demonstrated that variant calling methods based on deep neural networks can use local haplotyping information with long-reads to improve the genotyping accuracy.
View Article and Find Full Text PDFBladder Cancer
September 2023
Background: Despite recent drug development for non-muscle invasive bladder cancer (NMIBC), few therapies have been approved by the US Food and Drug Administration (FDA), and there remains an unmet clinical need. Bacillus Calmette-Guerin (BCG) supply issues underscore the importance of developing safe and effective drugs for NMIBC.
Objective: On November 18-19, 2021, the FDA held a public virtual workshop to discuss NMIBC research needs and potential trial designs for future development of effective therapies.
Transcranial focused ultrasound stimulation (tFUS) has emerged as a promising neuromodulation technique that delivers acoustic energy with high spatial resolution for inducing long-term potentiation (LTP)- or depression (LTD)-like plasticity. The variability in the primary effects of tFUS-induced plasticity could be due to different stimulation patterns, such as intermittent versus continuous, and is an aspect that requires further detailed exploration. In this study, we developed a platform to evaluate the neuromodulatory effects of intermittent and continuous tFUS on motor cortical plasticity before and after tFUS application.
View Article and Find Full Text PDFPhosphaphenalenes, extended π conjugates with the incorporation of phosphorus, are attractive avenues towards molecular materials for the applications in organic electronics, but their electron accepting ability have not been investigated. Herein we present systematic studies on the reductive behavior of a representative phosphaphenalene and its oxide by chemical and electrochemical methods. The chemical reduction of the phosphaphenalene by alkali metals reveals the facile P-C bond cleavage to form phosphaphenalenide anion, which functions as a transfer block for structure modification on the phosphorus atom.
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