Publications by authors named "Flint J"

Tertiary lymphoid structures play important roles in autoimmune and non-autoimmune conditions. While many of the molecular mechanisms involved in tertiary lymphoid structure formation have been identified, the cellular sources and temporal and spatial relationship remain unknown. Here we use combine single-cell RNA-sequencing, spatial transcriptomics and proteomics of minor salivary glands of patients with Sjogren's disease and Sicca Syndrome, with ex-vivo functional studies to construct a cellular and spatial map of key components involved in the formation and function of tertiary lymphoid structures.

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Major depressive disorder (MDD) often goes undiagnosed due to the absence of clear biomarkers. We sought to identify voice biomarkers for MDD and separate biomarkers indicative of MDD predisposition from biomarkers reflecting current depressive symptoms. Using a two-stage meta-analytic design to remove confounds, we tested the association between features representing vocal pitch and MDD in a multisite case-control cohort study of Chinese women with recurrent depression.

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Introduction: Climate change and its effects continue to threaten the stability of environments worldwide, impacting nearly every species. Although framing is an established technique in climate communication science, little has been done in communicating the climate change effects from an animal welfare perspective.

Objectives: The primary objective of this article is to present the synthesis of evidence in existing literature on the effects of communicating climate change as an animal welfare issue.

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American alligators () are an important apex predator of semiaquatic habitats of the southern United States. Commercial alligator farming has grown in the last several decades, leading to a need to understand the health conditions that affect this species to ensure appropriate management and welfare. The aims of this study were 1) to establish and describe normative data including results of common ophthalmic diagnostic tests and conjunctival flora, 2) document ocular pathology in this population, and 3) assess the effect of topical rocuronium bromide and 10% phenylephrine for facilitating pharmacologic mydriasis.

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  • * Turtles from the CDF showed signs of higher stress, including elevated glucose levels and altered blood metrics, compared to those from the PCM, which appeared healthier.
  • * Additionally, some turtles tested positive for Chlamydia, with a small number also showing co-infection with herpesvirus, highlighting the need to monitor the impacts of human-altered habitats on wildlife health.
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Importance: An accessible marker of both biological age and dementia risk is crucial to advancing dementia prevention and treatment strategies. Although frailty is a candidate for that role, the nature of the relationship between frailty and dementia is not well understood.

Objective: To clarify the temporal relationship between frailty and incident dementia by investigating frailty trajectories in the years preceding dementia onset.

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Pelvic bone metastases frequently result in severe pain and disability. Open surgical reconstruction is associated with a high complication and mortality rate. Percutaneous screw fixation is a minimally invasive treatment that is safe and effective for the management of periacetabular metastases.

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Background: Fellowship-trained orthopaedic oncologists in the US military provide routine clinical care and also must maintain readiness to provide combat casualty care. However, low oncologic procedure volume may hinder the ability of these surgeons to maintain relevant surgical expertise. Other low-volume specialties within the Military Health System (MHS) have established partnerships with neighboring civilian centers to increase procedure volume, but the need for similar partnerships for orthopaedic oncologists has not been examined.

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  • Large biobank samples allow researchers to combine detailed family histories and genetic data to investigate complex diseases.
  • The study introduces a new method called Pearson-Aitken Family Genetic Risk Scores (PA-FGRS) to estimate disease risk based on family medical histories.
  • Applying PA-FGRS to major depressive disorder (MDD) shows improved understanding of genetic factors and clinical variability, and enhances the effectiveness of genetic studies across different complex conditions.
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Major depressive disorder (MDD) often goes undiagnosed due to the absence of clear biomarkers. We sought to identify voice biomarkers for MDD and separate biomarkers indicative of MDD predisposition from biomarkers reflecting current depressive symptoms. Using a two-stage meta-analytic design to remove confounds, we tested the association between features representing vocal pitch and MDD in a multisite case-control cohort study of Chinese women with recurrent depression.

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  • Recent research has focused on speech-based automatic depression detection systems, typically classifying speakers as either Depressive or Non-depressive but lacking consideration for the varied distribution of depression characteristics in speech segments.
  • The proposed Speechformer-CTC framework leverages Connectionist Temporal Classification (CTC) to effectively model these non-uniform features without requiring detailed input-output alignment and introduces new policies for generating CTC labels.
  • Experimental results demonstrate significant improvements in detection performance across English and Mandarin datasets, achieving high F1-scores without needing granular phoneme-level transcription or extensive data augmentation.
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Identifying and refining clinically significant patient stratification is a critical step toward realizing the promise of precision medicine in asthma. Several peripheral blood hallmarks, including total peripheral blood eosinophil count (BEC) and immunoglobulin E (IgE) levels, are routinely used in asthma clinical practice for endotype classification and predicting response to state-of-the-art targeted biologic drugs. However, these biomarkers appear ineffective in predicting treatment outcomes in some patients, and they differ in distribution between racially and ethnically diverse populations, potentially compromising medical care and hindering health equity due to biases in drug eligibility.

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Background And Objectives: Surgical treatment of soft tissue sarcoma (STS) involves wide resection of the tumor, which can necessitate soft tissue reconstruction with local or free tissue flaps. This retrospective study compares cost, surgical and oncologic outcomes between patients undergoing reconstruction with immediate versus delayed flap coverage following STS resection.

Methods: Thirty-four patients who underwent planned flap reconstruction following resection of primary STS were identified retrospectively.

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  • Fibrotic hypersensitivity pneumonitis (FHP) is an interstitial lung disease linked to unclear immune reactions, and researchers studied immune cells from various patient groups using single-cell RNA sequencing.
  • The analysis revealed an increase in specific immune cells, including classical monocytes and GZM cytotoxic T cells, in FHP patients compared to controls and those with idiopathic pulmonary fibrosis (IPF).
  • These findings highlight unique immune disturbances in FHP, suggesting potential new biomarkers and treatment strategies based on the distinct inflammatory responses observed in the disease.
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Frailty is a complex trait. Twin studies and recent Genome-Wide Association Studies have demonstrated a strong genetic basis of frailty but there remains a lack of genetic studies exploring genetic prediction of Frailty. Previous work has shown that a single polygenic predictor - represented by a Frailty polygenic score - predicts Frailty, measured via the frailty index, in independent samples within the United Kingdom.

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Frailty is a complex trait. Twin studies and high-powered Genome Wide Association Studies conducted in the UK Biobank have demonstrated a strong genetic basis of frailty. The present study utilized summary statistics from a Genome Wide Association Study on the Frailty Index to create and test the predictive power of frailty polygenic risk scores (PRS) in two independent samples - the Lothian Birth Cohort 1936 (LBC1936) and the English Longitudinal Study of Ageing (ELSA) aged 67-84 years.

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Frailty may represent a modifiable risk factor for dementia, but the direction of that association remains uncertain. We investigated frailty trajectories in the years preceding dementia onset using data from 23,672 participants (242,760 person-years of follow-up, 2,906 cases of incident dementia) across four cohort studies in the United States and United Kingdom. Bayesian non-linear models revealed accelerations in frailty trajectories 4-9 years before incident dementia.

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Changes in peripheral blood cell populations have been observed, but not detailed, at single-cell resolution in idiopathic pulmonary fibrosis (IPF). We sought to provide an atlas of the changes in the peripheral immune system in stable and progressive IPF. Peripheral blood mononuclear cells (PBMCs) from patients with IPF and control subjects were profiled using 10× chromium 5' single-cell RNA sequencing.

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The genetic influence on human vocal pitch in tonal and non-tonal languages remains largely unknown. In tonal languages, such as Mandarin Chinese, pitch changes differentiate word meanings, whereas in non-tonal languages, such as Icelandic, pitch is used to convey intonation. We addressed this question by searching for genetic associations with interindividual variation in median pitch in a Chinese major depression case-control cohort and compared our results with a genome-wide association study from Iceland.

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Knowing the genes involved in quantitative traits provides an entry point to understanding the biological bases of behavior, but there are very few examples where the pathway from genetic locus to behavioral change is known. To explore the role of specific genes in fear behavior, we mapped three fear-related traits, tested fourteen genes at six quantitative trait loci (QTLs) by quantitative complementation, and identified six genes. Four genes, Lamp, Ptprd, Nptx2, and Sh3gl, have known roles in synapse function; the fifth, Psip1, was not previously implicated in behavior; and the sixth is a long non-coding RNA, 4933413L06Rik, of unknown function.

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The proposed method focuses on speaker disentanglement in the context of depression detection from speech signals. Previous approaches require patient/speaker labels, encounter instability due to loss maximization, and introduce unnecessary parameters for adversarial domain prediction. In contrast, the proposed unsupervised approach reduces cosine similarity between latent spaces of depression and pre-trained speaker classification models.

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Dengue virus (DENV) infection causes 390 million infections per year and 40,000 deaths globally. It is endemic in many countries in Asia, Africa, the Americas, the Caribbean, and Oceania. Dengue is endemic in Timor-Leste year-round, but peak transmission occurs during the rainy season.

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  • Significant advancements have been made in using data from smartphones and wearables to track depressive moods over the past decade, but many studies struggle with replicability and validity of depression measures.
  • This study involved 183 individuals and combined adaptive testing with continuous behavioral data over 40 weeks, achieving high prediction accuracy of future mood based on digital data.
  • The findings demonstrate the potential for more personalized behavioral assessments in mental health research, allowing for predictions of symptom severity weeks ahead.
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Speech signals are valuable biomarkers for assessing an individual's mental health, including identifying Major Depressive Disorder (MDD) automatically. A frequently used approach in this regard is to employ features related to speaker identity, such as speaker-embeddings. However, over-reliance on speaker identity features in mental health screening systems can compromise patient privacy.

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Knowing the genes involved in quantitative traits provides a critical entry point to understanding the biological bases of behavior, but there are very few examples where the pathway from genetic locus to behavioral change is known. Here we address a key step towards that goal by deploying a test that directly queries whether a gene mediates the effect of a quantitative trait locus (QTL). To explore the role of specific genes in fear behavior, we mapped three fear-related traits, tested fourteen genes at six QTLs, and identified six genes.

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