Publications by authors named "Brian Cox"

Article Synopsis
  • - Stem cell-based embryo models are essential for studying early human development, but their effectiveness depends on how closely they mimic real embryos at the molecular, cellular, and structural levels.
  • - Researchers created a comprehensive reference dataset by integrating six existing datasets that track human development from the zygote stage to the gastrula stage, providing a benchmark for comparing human embryo models.
  • - Using an advanced analysis method called stabilized Uniform Manifold Approximation and Projection, the new reference helps identify cell types in various embryo models, revealing potential misannotations without proper reference comparisons.
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Mild traumatic brain injury (mTBI) increases the risk of affective disorders, anxiety and substance use disorder. The lateral habenula (LHb) plays an important role in pathophysiology of psychiatric disorders. Recently, we demonstrated a causal link between mTBI-induced LHb hyperactivity due to excitation/inhibition (E/I) imbalance and motivational deficits in male mice using a repetitive closed head injury mTBI model.

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Introduction: Several landmark randomized-controlled trials (RCTs) have demonstrated the efficacy of sodium-glucose co-transport 2 (SGLT2) inhibitors in reducing all-cause mortality, cardiovascular (CV) mortality and heart failure (HF) hospitalizations. Much interest surrounds their mechanism of action and whether they have direct effects on reverse cardiac remodelling. Therefore, we conducted a meta-analysis of placebo controlled RCTs evaluating the impact of SGLT2 inhibition on imaging derived markers of reverse cardiac remodelling in patients with HF.

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Background: The major burden of cervical cancer occurs in low- and middle-income countries. In Ghana, it is the second most common cancer among women. Infection with high-risk human papilloma virus (HPV) has been established as the cause of cervical cancer.

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Mild traumatic brain injury (mTBI) is a significant health burden due to mTBI-related chronic debilitating cognitive and psychiatric morbidities. Recent evidence from our laboratory suggests a possible dysregulation within reward/motivational circuit function at the level of a subcortical structure, the lateral habenula (LHb), where we demonstrated a causal role for hyperactive LHb in mTBI-induced motivational deficits in self-care grooming behavior in young adult male mice when exposed to mTBI during late adolescence (at ∼8 weeks old). In this study, we extended this observation by further characterizing neurobehavioral effects of this repetitive closed head injury model of mTBI in both young adult male and female mice on LHb excitability, corticotropin releasing factor (CRF) modulation of LHb activity, and behavioral responses of motivation to self-care behavior and approach versus avoidance behavior in the presence of a social- or threat-related stimulus.

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Mild traumatic brain injury (mTBI) is a significant health burden due to mTBI-related chronic debilitating cognitive and psychiatric morbidities. Recent evidence from our laboratory suggests a possible dysregulation within reward/motivational circuit function at the level of a subcortical structure, the lateral habenula (LHb), where we demonstrated a causal role for hyperactive LHb in mTBI-induced motivational deficits in self-care grooming behavior in young adult male mice when exposed to mTBI injury during late adolescence (at ~8 weeks old). Here we extended this observation by further characterizing neurobehavioral effects of this repetitive closed head injury model of mTBI in both young adult male and female mice on LHb excitability, corticotropin releasing factor (CRF) modulation of LHb activity, and behavioral responses of motivation to self-care behavior, and approach versus avoidance behavior in the presence of a social- or threat-related stimulus.

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Mild traumatic brain injury (mTBI) increases the risk of cognitive deficits, affective disorders, anxiety and substance use disorder in affected individuals. Substantial evidence suggests a critical role for the lateral habenula (LHb) in pathophysiology of psychiatric disorders. Recently, we demonstrated a causal link between persistent mTBI-induced LHb hyperactivity due to synaptic excitation/inhibition (E/I) imbalance and motivational deficits in self-care grooming behavior in young adult male mice using a repetitive closed head injury mTBI model.

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Introduction: Over the course of 2023, numerous key clinical trials with valuable contributions to clinical cardiology were published or presented at major international conferences. This review seeks to summarise these trials and reflect on their clinical context.

Methods: The authors collated and reviewed clinical trials presented at major cardiology conferences during 2023 including the American College of Cardiology (ACC), European Association for Percutaneous Cardiovascular Interventions (EuroPCR), European Society of Cardiology (ESC), Transcatheter Cardiovascular Therapeutics (TCT), American Heart Association (AHA), European Heart Rhythm Association (EHRA), Society for Cardiovascular Angiography and Interventions (SCAI), TVT-The Heart Summit (TVT) and Cardiovascular Research Technologies (CRT).

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The scaffolding A-kinase anchoring protein 150 (AKAP150) is critically involved in kinase and phosphatase regulation of synaptic transmission/plasticity, and neuronal excitability. Emerging evidence also suggests that AKAP150 signaling may play a key role in brain's processing of rewarding/aversive experiences, however its role in the lateral habenula (LHb, as an important brain reward circuitry) is completely unknown. Using whole cell patch clamp recordings in LHb of male wildtype and ΔPKA knockin mice (with deficiency in AKAP-anchoring of PKA), here we show that the genetic disruption of PKA anchoring to AKAP150 significantly reduces AMPA receptor-mediated glutamatergic transmission and prevents the induction of presynaptic endocannabinoid-mediated long-term depression in LHb neurons.

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Objectives: To investigate indicators of potentially hazardous alcohol use among older adults living in a region with high substance use stigma.

Methods: Patients at a university-affiliated geriatrics clinic in the Deep South of theUS completed behavioral health screenings including self-reported alcohol use, symptoms of depression or anxiety, and cognitive functioning between 2018 and 2022.

Results: Participants ( = 278) averaged 76.

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Background: The burden of cancer can be altered by screening. The field of cancer screening is constantly evolving; from the initiation of program for new cancer types as well as exploring innovative screening strategies (e.g.

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Bridging the healthcare access gap and addressing COVID-19 vaccine hesitancy among rural-dwelling Black American adults residing in the Deep South require involvement of faith-based leaders in the community. This study explored perceived barriers and resources to meeting community needs, including vaccination, during the COVID-19 pandemic as reported by 17 Black American church leaders in the rural West Alabama Black Belt geographic region in May 2022. The main themes that emerged included (1) attending to community impact of COVID-19 illness and death; (2) maximizing health literacy and diminishing vaccine hesitancy through engaging in preventive health practices and sharing public health information; (3) addressing challenges created or exacerbated by COVID-19, including reduction in in-person attendance (particularly among adolescents and young adults), limited access to and literacy with technology, and political perceptions influencing engagement in preventive health behaviors; (4) maximizing technological solutions to increase attendance in the church; and (5) engaging in solution-focused and innovative initiatives to meet the identified needs in the congregation and community.

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Background: Although young-age-of-onset colorectal cancer is increasing in incidence, lack of screening leads to symptomatic presentation, often with rectal bleeding. Because most cancers in patients younger than 50 years are left-sided, flexible sigmoidoscopy is a reasonable way of investigating bleeding in these patients.

Objective: To predict which patients undergoing flexible sigmoidoscopy for outlet-type rectal bleeding need a full colonoscopy.

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Article Synopsis
  • The study focused on understanding SCN5A-related cardiomyopathies by creating ventricular cardiomyocytes from stem cells of a dilated cardiomyopathy patient with the R222Q mutation.
  • Using heart-on-a-chip biowires, researchers found that the R222Q mutation led to arrhythmias, altered sodium channel properties, and decreased heart muscle contractility compared to controls.
  • RNA sequencing revealed significant differences in gene regulation affecting calcium handling and sarcomere structure, highlighting the mutation's impact on both cardiac electrical activity and mechanical stability.
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Context: Recent data suggest mesenteric tumor deposits (MTDs) indicate poor prognosis in small bowel well-differentiated neuroendocrine tumors (SB-NETs), including compared to positive lymph nodes, making their distinction crucial.

Objective: To study interobserver agreement in distinguishing SB-NET MTDs from positive nodes.

Design: Virtual slides from 36 locally metastatic SB-NET foci were shared among 7 gastrointestinal pathologists, who interpreted each as an MTD or a positive node.

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Motivation: The method of genome-wide association studies (GWAS) and metabolomics combined provide an quantitative approach to pinpoint metabolic pathways and genes linked to specific diseases; however, such analyses require both genomics and metabolomics datasets from the same individuals/samples. In most cases, this approach is not feasible due to high costs, lack of technical infrastructure, unavailability of samples, and other factors. Therefore, an unmet need exists for a bioinformatics tool that can identify gene loci-associated polymorphic variants for metabolite alterations seen in disease states using standalone metabolomics.

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Capecitabine is a commonly used oral chemotherapeutic agent. Gastrointestinal (GI) side effects are clinically well-known, however, the histopathologic changes have not been comprehensively studied. This study describes the largest case series (8 patients) characterizing the histopathology of capecitabine-induced GI injury.

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The European aviation sector must substantially reduce climate impacts to reach net-zero goals. This reduction, however, must not be limited to flight CO emissions since such a narrow focus leaves up to 80% of climate impacts unaccounted for. Based on rigorous life-cycle assessment and a time-dependent quantification of non-CO climate impacts, here we show that, from a technological standpoint, using electricity-based synthetic jet fuels and compensating climate impacts via direct air carbon capture and storage (DACCS) can enable climate-neutral aviation.

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Positive screening tests require investigation, usually by specialists. Specialist services are known to be limited. The planning of screening programmes must first include a model of existing diagnostic and follow-up services of symptomatic patients so that the added impact of the extra referrals required for screening can be estimated.

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GDM is a strong risk factor for progression to T2D after pregnancy. Although both GDM and T2D exhibit heterogeneity, the link between the distinct heterogeneity of GDM and incident T2D has not been established. Herein, we evaluate early postpartum profiles of women with recent GDM who later developed incident T2D using a soft clustering method, followed by the integration of both clinical phenotypic variables and metabolomics to characterize these heterogeneous clusters/groups clinically and their molecular mechanisms.

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Introduction: Over the course of 2022, numerous key clinical trials with valuable contributions to clinical cardiology were published or presented at major international conferences. This review seeks to summarise these trials and to reflect on their clinical context.

Methods: The authors reviewed clinical trials presented at major cardiology conferences during 2022, including the American College of Cardiology (ACC), European Association for Percutaneous Cardiovascular Interventions (EuroPCR), European Society of Cardiology (ESC), Transcatheter Cardiovascular Therapeutics (TCT), American Heart Association (AHA), European Heart Rhythm Association (EHRA), Society for Cardiovascular Angiography and Interventions (SCAI), TVT-The Heart Summit (TVT) and Cardiovascular Research Technologies (CRT).

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Objectives: This study examines the clinical-pathological profiles of patients with glycogenic hepatopathy in a contemporary cohort of patients at an adult acute care hospital.

Methods: Liver biopsies with glycogenic hepatopathy were retrieved from the departmental surgical pathology database, the histological findings were studied, and the clinical findings were reviewed.

Results: Five cases of glycogenic hepatopathy were found, including cases associated with type 1 diabetes mellitus (n = 1), type 2 diabetes mellitus (n = 1), corticosteroids (n = 2), and anorexia (n = 2, including the patient with type 1 diabetes).

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Hit generation is a crucial step in drug discovery that will determine the speed and chance of success of identifying drug candidates. Many strategies are now available to identify chemical starting points, or hits, and each biological target warrants a tailored approach. In this set of best practices, we detail the essential approaches for target centric hit generation and the opportunities and challenges they come with.

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