Improving neurological deficits secondary to transverse myelitis using epidural spinal cord stimulation: illustrative cases.

Background: Epidural spinal cord stimulation (eSCS) is canonically used for the treatment of intractable, chronic pain. Recent efforts have successfully utilized eSCS to improve neurological deficits in patients with spinal cord injury. However, there is a paucity of literature on the use of eSCS for demyelinating conditions, with no prior case reports examining eSCS among patients with transverse myelitis (TM).

Utilizing kinematic analysis of postural instability as an objective measure to aid in distinguishing between normal pressure hydrocephalus and Parkinson's disease.

Objective: Patients with normal pressure hydrocephalus (NPH) and Parkinson's Disease (PD) can clinically appear quite similar at baseline evaluation. We sought to investigate the use of kinematic assessment of postural instability (PI) using inertial measurement units (IMUs) as a mechanism of differentiation between the two disease processes.

Methods: 20 patients with NPH, 55 patients with PD, and 56 age-matched, healthy controls underwent quantitative pull test examinations while wearing IMUs at baseline.

Changes in Cerebrovascular Procedures and Outcomes During COVID-19 Using the National Surgery Quality Improvement Project.

Objective: Explore the consequences of the coronavirus pandemic (COVID-19) on patients suffering from cerebrovascular disorders necessitating interventions.

Methods: Using the National Surgical Quality Improvement Program database, patients with cerebrovascular disease who underwent procedures before (2018-2019) and during (2020-2021) COVID-19 were identified. ICD-10 and Current Procedure Terminology codes were employed to classify diseases and elective cases, respectively.

Recovery of volitional movement with epidural stimulation after "complete" spinal cord injury due to gunshot: A case report and literature review.

Background: Epidural spinal cord stimulation (eSCS) restores volitional movement and improves autonomic function after nonpenetrating and traumatic spinal cord injury (SCI). There is limited evidence of its utility for penetrating SCI (pSCI).

Case Description: A 25-year-old male sustained a gunshot wound (GSW) resulting in T6 motor/sensory paraplegia and complete loss of bowel and bladder function.

Racial disparities in recommendations for surgical resection of primary brain tumours: a registry-based cohort analysis.

Background: Disparities in treatment and outcomes disproportionately affect minority ethnic and racial populations in many surgical fields. Although substantial research in racial disparities has focused on outcomes, little is known about how surgeon recommendations can be influenced by patient race. The aim of this study was to investigate racial and socioeconomic disparities in the surgical management of primary brain tumors.

Resection of disseminated recurrent myxopapillary ependymoma with more than 4-year follow-up: operative nuance for prolonged prone position. Illustrative case.

Background: Symptomatic disseminated myxopapillary ependymoma (MPE) in a young person presents a daunting challenge because the risks of prolonged prone positioning and spinal cord injury may outweigh the likelihood of attaining the benefit of gross total resection.

Observations: The authors reported the case of a 15-year-old girl with five discrete recurrent spinal cord ependymomas. The patient received a 25-hour surgical procedure for gross total resection of the tumors and fusion over an approximately 33-hour period.

Rates of operative intervention for infection after synthetic or autologous cranioplasty: a National Readmissions Database analysis.

Objective: The aim of this study was to characterize the clinical utilization and associated charges of autologous bone flap (ABF) versus synthetic flap (SF) cranioplasty and to characterize the postoperative infection risk of SF versus ABF using the National Readmissions Database (NRD).

Methods: The authors used the publicly available NRD to identify index hospitalizations from October 2015 to December 2018 involving elective ABF or SF cranioplasty after traumatic brain injury (TBI) or stroke. Subsequent readmissions were further characterized if patients underwent neurosurgical intervention for treatment of infection or suspected infection.

Readmission risk of malignant brain tumor patients undergoing laser interstitial thermal therapy (LITT) and stereotactic needle biopsy (SNB): a covariate balancing weights analysis of the National Readmissions Database (NRD).

Purpose: Despite procedural similarities between laser interstitial thermal therapy (LITT) and stereotactic needle biopsy (SNB), LITT induces delayed, pro-inflammatory responses not associated with SNB that may increase the risk of readmission within 30- or 90- days. Here, we explore this hypothesis.

Methods: We queried the National Readmissions Database (NRD, 2010-18) for malignant brain tumor patients who underwent elective LITT or SNB using International Classification of Diseases codes.

High throughput and high confidence sequence variant analysis in therapeutic antibodies using Evosep One liquid chromatography tandem mass spectrometry with synthetic heavy peptides.

Sequence variants are anomalous misincorporations of amino acids into the primary structure of therapeutic antibodies during DNA replication and protein biosynthesis. As these low abundance variants contribute to molecular heterogeneity and could negatively impact the safety and efficacy of a protein therapeutic, analytical methods like liquid chromatography tandem mass spectrometry (LC-MS) are used to monitor them with the goal of establishing control strategies that limit their occurrence. Current LC-MS strategies depend on relatively long gradients that minimize coelution between abundant non-variant peptide peaks and trace-level variants to limit ion suppression that can potentially conceal the latter.

The Effects of the COVID-19 Pandemic on Penetrating Neurotrauma at a Level 1 Trauma Center.

Background/objective: The COVID-19 pandemic has had a profound impact on the global delivery of health care. Recent data suggest a possible impact of the pandemic on patterns of neurotrauma. The aim was to assess the impact of the pandemic on the incidence of neurotrauma, with a focus on cranial gunshot wounds (cGSWs) at a large Midwestern level 1 trauma center.

Testing mechanisms of DNA sliding by architectural DNA-binding proteins: dynamics of single wild-type and mutant protein molecules in vitro and in vivo.

Architectural DNA-binding proteins (ADBPs) are abundant constituents of eukaryotic or bacterial chromosomes that bind DNA promiscuously and function in diverse DNA reactions. They generate large conformational changes in DNA upon binding yet can slide along DNA when searching for functional binding sites. Here we investigate the mechanism by which ADBPs diffuse on DNA by single-molecule analyses of mutant proteins rationally chosen to distinguish between rotation-coupled diffusion and DNA surface sliding after transient unbinding from the groove(s).

Pattern of technology diffusion in the adoption of stereotactic laser interstitial thermal therapy (LITT) in neuro-oncology.

Purpose: Understanding factors that influence technology diffusion is central to clinical translation of novel therapies. We characterized the pattern of adoption for laser interstitial thermal therapy (LITT), also known as stereotactic laser ablation (SLA), in neuro-oncology using the National Inpatient Sample (NIS) database.

Methods: We identified patients age ≥ 18 in the NIS (2012-2018) with a diagnosis of primary or metastatic brain tumor that underwent LITT or craniotomy.

Control of the Serine Integrase Reaction: Roles of the Coiled-Coil and Helix E Regions in DNA Site Synapsis and Recombination.

Bacteriophage serine integrases catalyze highly specific recombination reactions between defined DNA segments called sites. These reactions are reversible depending upon the presence of a second phage-encoded directionality factor. The bipartite C-terminal DNA-binding region of integrases includes a recombinase domain (RD) connected to a zinc-binding domain (ZD), which contains a long flexible coiled-coil (CC) motif that extends away from the bound DNA.

Electron Transfer Dissociation Parameter Optimization Using Design of Experiments Increases Sequence Coverage of Monoclonal Antibodies.

Middle-down analysis of monoclonal antibodies (mAbs) by tandem mass spectrometry (MS) can provide detailed insight into their primary structure with minimal sample preparation. The middle-down approach uses an enzyme to cleave mAbs into Fc/2, LC, and Fd subunits that are then analyzed by reversed phase liquid chromatography tandem mass spectrometry (RPLC-MS). As maximum sequence coverage is desired to obtain meaningful structural information at the subunit level, a host of dissociation methods have been developed, and sometimes combined, to bolster fragmentation and increase the number of identified fragments.

The HMGB chromatin protein Nhp6A can bypass obstacles when traveling on DNA.

DNA binding proteins rapidly locate their specific DNA targets through a combination of 3D and 1D diffusion mechanisms, with the 1D search involving bidirectional sliding along DNA. However, even in nucleosome-free regions, chromosomes are highly decorated with associated proteins that may block sliding. Here we investigate the ability of the abundant chromatin-associated HMGB protein Nhp6A from Saccharomyces cerevisiae to travel along DNA in the presence of other architectural DNA binding proteins using single-molecule fluorescence microscopy.

Combination of FAIMS, Protein A Depletion, and Native Digest Conditions Enables Deep Proteomic Profiling of Host Cell Proteins in Monoclonal Antibodies.

Host cell proteins (HCPs) are residual impurities generated by the expression cell line during the production of biopharmaceuticals. Although the majority of these contaminants are removed during purification, HCPs can represent a considerable risk to the efficacy and safety of a therapeutic protein if not actively monitored. The enzyme-linked immunosorbent assay (ELISA) is commonly used throughout production to monitor HCP levels but has limited ability to identify novel HCPs or provide detailed quantification.

Cooperative DNA binding by proteins through DNA shape complementarity.

Localized arrays of proteins cooperatively assemble onto chromosomes to control DNA activity in many contexts. Binding cooperativity is often mediated by specific protein-protein interactions, but cooperativity through DNA structure is becoming increasingly recognized as an additional mechanism. During the site-specific DNA recombination reaction that excises phage λ from the chromosome, the bacterial DNA architectural protein Fis recruits multiple λ-encoded Xis proteins to the attR recombination site.

Multiple serine transposase dimers assemble the transposon-end synaptic complex during IS-family transposition.

IS-family transposons are unusual because they do not have terminal inverted repeats or generate target site duplications. They encode two protein-coding genes, but only is required for transposition. Our X-ray structures confirm that TnpA is a member of the serine recombinase (SR) family, but the chemically-inactive quaternary structure of the dimer, along with the N-terminal location of the DNA binding domain, are different from other SRs.

The State of Data in Healthcare: Path Towards Standardization.

Coupled with the rise of data science and machine learning, the increasing availability of digitized health and wellness data has provided an exciting opportunity for complex analyses of problems throughout the healthcare domain. Whereas many early works focused on a particular aspect of patient care, often drawing on data from a specific clinical or administrative source, it has become clear such a single-source approach is insufficient to capture the complexity of the human condition. Instead, adequately modeling health and wellness problems requires the ability to draw upon data spanning multiple facets of an individual's biology, their care, and the social aspects of their life.

FraudBuster: Reducing Fraud in an Auto Insurance Market.

Nonstandard insurers suffer from a peculiar variant of fraud wherein an overwhelming majority of claims have the semblance of fraud. We show that state-of-the-art fraud detection performs poorly when deployed at underwriting. Our proposed framework "FraudBuster" represents a new paradigm in predicting segments of fraud at underwriting in an interpretable and regulation compliant manner.

High Free-Energy Barrier of 1D Diffusion Along DNA by Architectural DNA-Binding Proteins.

Architectural DNA-binding proteins function to regulate diverse DNA reactions and have the defining property of significantly changing DNA conformation. Although the 1D movement along DNA by other types of DNA-binding proteins has been visualized, the mobility of architectural DNA-binding proteins on DNA remains unknown. Here, we applied single-molecule fluorescence imaging on arrays of extended DNA molecules to probe the binding dynamics of three structurally distinct architectural DNA-binding proteins: Nhp6A, HU, and Fis.

Facilitated dissociation of transcription factors from single DNA binding sites.

The binding of transcription factors (TFs) to DNA controls most aspects of cellular function, making the understanding of their binding kinetics imperative. The standard description of bimolecular interactions posits that TF off rates are independent of TF concentration in solution. However, recent observations have revealed that proteins in solution can accelerate the dissociation of DNA-bound proteins.

Control of Recombination Directionality by the Listeria Phage A118 Protein Gp44 and the Coiled-Coil Motif of Its Serine Integrase.

The serine integrase of phage A118 catalyzes integrative recombination between on the phage and a specific locus on the chromosome of , but it is unable to promote excisive recombination between the hybrid and sites found on the integrated prophage without assistance by a recombination directionality factor (RDF). We have identified and characterized the phage-encoded RDF Gp44, which activates the A118 integrase for excision and inhibits integration. Gp44 binds to the C-terminal DNA binding domain of integrase, and we have localized the primary binding site to be within the mobile coiled-coil (CC) motif but distinct from the distal tip of the CC that is required for recombination.