Publications by authors named "Frost N"

Individuals with joint hypermobility and the Ehlers-Danlos Syndromes (EDS) are disproportionately affected by neuraxial dysfunction and Central Nervous System (CNS) disorders: such as Spontaneous Intracranial Hypotension (SIH) due to spinal cerebrospinal fluid (CSF) leaks, Upper Cervical Instability (UCI; including craniocervical or atlantoaxial instability (CCI/AAI)), Occult Tethered Cord Syndrome (TCS), Chiari Malformation (CM) and Idiopathic Intracranial Hypertension (IIH). The neuraxis comprises the parts of the nervous system (brain, nerves, spinal cord) along the craniospinal axis of the body. Neuraxial tissue includes all tissue structures that comprise, support, sheath, and connect along the neuraxis and peripheral nerves.

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  • This study focuses on the role of Thyroid Transcription Factor-1 (TTF-1) in lung adenocarcinoma (LUAD) brain metastases, specifically its predictive value and relationship with patient outcomes.
  • Researchers analyzed data from 245 patients who had brain metastases, looking at factors like tumor volume and survival rates based on TTF-1 expression status.
  • Results indicate that TTF-1 negative patients had larger tumors, higher proliferation rates, and worse survival outcomes, suggesting that TTF-1 negativity signifies a more aggressive form of the disease, warranting further study on its underlying mechanisms.
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The increasing use of machine learning (ML) in public administration requires that we think carefully about the political and legal constraints imposed on public decision making. These developments confront us with the following interrelated questions: can algorithmic public decisions be truly 'public'? And, to what extent does the use of ML models compromise the 'publicness' of such decisions? This article is part of a broader inquiry into the myriad ways in which digital and AI technologies transform the fabric of our democratic existence by mutating the 'public'. Focusing on the site of public administration, the article develops a conception of publicness that is grounded in a view of public administrations as communities of practice.

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To investigate the perceptions of lactation experiences of neurology faculty and the impact of lactation time on academic achievement. This was a cross-sectional study utilizing a survey administered across 19 academic neurology centers in the United States. Respondents self-identified as having children and answered questions about lactation at work.

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Quantifying immediate early gene expression as a marker of cellular activity in single-nuclei RNA sequencing data allows for the identification of neurons involved in specific behaviors. Here, we present a protocol for generating single-nuclei libraries from the mouse brain and identifying active cell populations following social interactions. We describe steps for the dissection, preparation, and analysis of the prefrontal cortex, hippocampus, and cerebellum.

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  • TTF-1 immunohistochemistry is commonly used to identify primary pulmonary adenocarcinomas, but it can also appear in various other cancer types.
  • In a study involving 17,772 tumor samples, TTF-1 was found in 82 different tumor categories, indicating a broad range of malignancies where it may be present, spanning from thyroid cancers to neuroendocrine tumors.
  • Although TTF-1 shows high sensitivity for distinguishing pulmonary adenocarcinomas, its specificity is low; combining TTF-1 with Napsin-A significantly enhances diagnostic accuracy.
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Background And Aims: Children with very early onset inflammatory bowel disease (VEO-IBD) are uniquely at risk of inadequate infliximab (IFX) exposure. We studied the association between standard body weight (BW)-based and body surface area (BSA)-based dosing strategies and outcomes.

Methods: We identified VEO-IBD patients treated with IFX before 9 years at a single center.

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Social interactions are encoded by the coordinated activity of heterogeneous cell types within distributed brain regions including the medial prefrontal cortex (mPFC). However, our understanding of the cell types which comprise the social ensemble has been limited by available mouse lines and reliance on single marker genes. We identified differentially active neuronal populations during social interactions by quantifying immediate-early gene (IEG) expression using snRNA-sequencing.

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Intersection of gender and race and/or ethnicity in academic medicine is understudied; we aim to understand these factors in relation to scholarly achievements for neurology faculty. Faculty from 19 US neurology departments completed a survey (2021-2022) to report rank, leadership positions, publications, funded projects, awards, and speaker invitations. Regression analyses examined effects of gender, race, and their intersectionality on these achievements.

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Objective: To identify the characteristics that distinguish occupationally well outliers (OWO), a subset of academic psychiatrists and neurologists with consistently high professional fulfillment and low burnout, from their counterparts with lower levels of occupational well-being.

Participants And Methods: Participants included faculty physicians practicing psychiatry and neurology in academic medical centers affiliated with the Professional Well-being Academic Consortium. In this prospective, longitudinal study, a mixed qualitative and quantitative approach was used.

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This overview provides a thorough review of current treatment approaches for first-line management of nononcogenic addicted non-small cell lung cancer. We also address pertinent clinical decision-making queries encountered in everyday practice, such as the optimal treatment strategy for PD-L1-high patients, predictive factors for response to immune checkpoint inhibitors (ICI) both in terms of patient and cancer characteristics, the potential benefits of dual checkpoint blockade, and the unresolved issue of safe discontinuation strategies for long-term responders. Around one in five patients falls into this latter category while the majority develop either primary or acquired resistance to ICI-based first-line therapy, necessitating effective subsequent lines of treatment.

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Thalamic dysfunction has been implicated in multiple psychiatric disorders. We sought to study the mechanisms by which abnormalities emerge in the context of the 22q11.2 microdeletion, which confers significant genetic risk for psychiatric disorders.

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Article Synopsis
  • - Sotorasib, a KRAS p.G12C-inhibitor, was studied in real-world settings for patients with advanced non-small cell lung cancer (NSCLC) who had received prior treatments, revealing a 38.7% objective response rate and a median overall survival of 9.8 months.
  • - Data was collected from 163 patients in a compassionate use program, where a significant portion had poor performance status and existing brain metastases, and some required dose reductions or discontinuation.
  • - The study found that factors like PD-L1 expression and KEAP1 mutations influenced efficacy, with KEAP1 mutations associated with worse survival outcomes, while other mutations did not significantly affect response or survival.
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Background: Emerging evidence suggests that treatment of NSCLC brain metastases with immune checkpoint inhibitors (ICIs) is associated with response rates similar to those of extracranial disease. Programmed death-ligand 1 (PD-L1) tumor proportion score (TPS) serves as a predictive biomarker for ICI response. However, the predictive value of brain metastasis-specific (intracranial) PD-L1 TPS is not established.

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  • The study investigates the effectiveness of chemotherapy (CHT) and immunotherapy (IO) in treating non-small cell lung cancer (NSCLC) with MET exon 14 skipping (METΔ14ex), involving 110 patients over six years in Germany.
  • Results indicate that combined CHT-IO treatment leads to better progression-free survival (PFS) and objective response rates compared to CHT alone, although overall survival (OS) was similar between CHT-IO and IO monotherapy.
  • Additionally, patients with TP53 mutations showed improved outcomes with treatment, while never-smokers were at a greater risk for primary progressive disease with IO.
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Literature evidence on sub-cutaneous drain insertion in severe surgical emphysema (SE) is lacking. We retrospectively reviewed the clinical notes of 5 patients who underwent insertion of sub-cutaneous drains to manage SE of various aetiologies between September 2022 to August 2023 in a single district general hospital in the UK. Case history, outcome following sub-cutaneous drain insertion, and side effects due to the procedure were collected.

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Glioblastoma presents characteristically with an exuberant, poorly functional vasculature that causes malperfusion, hypoxia and necrosis. Despite limited clinical efficacy, anti-angiogenesis resulting in vascular normalization remains a promising therapeutic approach. Yet, fundamental questions concerning anti-angiogenic therapy remain unanswered, partly due to the scale and resolution gap between microscopy and clinical imaging and a lack of quantitative data readouts.

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Reliable representations of information regarding complex behaviors including social interactions require the coordinated activity of heterogeneous cell types within distributed brain regions. Activity in the medial prefrontal cortex is critical in regulating social behavior, but our understanding of the specific cell types which comprise the social ensemble has been limited by available mouse lines and molecular tagging strategies which rely on the expression of a single marker gene. Here we sought to quantify the heterogeneous neuronal populations which are recruited during social interaction in parallel in a non-biased manner and determine how distinct cell types are differentially active during social interactions.

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Objectives: Thyroid transcription factor 1 (TTF-1) is a well-established independent prognostic factor in lung adenocarcinoma (LUAD), irrespective of stage. This study aims to determine if TTF-1's prognostic impact is solely based on histomorphological differentiation (tumor grading) or if it independently relates to a biologically more aggressive phenotype. We analyzed a large bi-centric LUAD cohort to accurately assess TTF-1's prognostic value in relation to tumor grade.

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Introduction: Programmed death-ligand 1 expression currently represents the only validated predictive biomarker for immune checkpoint inhibition in metastatic NSCLC in the clinical routine, but it has limited value in distinguishing responses. Assessment of KRAS and TP53 mutations (mut) as surrogate for an immunosupportive tumor microenvironment (TME) might help to close this gap.

Methods: A total of 696 consecutive patients with programmed death-ligand 1-high (≥50%), nonsquamous NSCLC, having received molecular testing within the German National Network Genomic Medicine Lung Cancer between 2017 and 2020, with Eastern Cooperative Oncology Group performance status less than or equal to 1 and pembrolizumab as first-line palliative treatment, were included into this retrospective cohort analysis.

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