Publications by authors named "Flanagan M"

Trans-active response DNA-binding protein-43 (TDP-43) is the major pathological protein in motor neuron disease and TDP-43 pathology has been described in the brains of up to 50% of patients with Alzheimer disease (AD). Hippocampal sclerosis of aging (HS-A), an age-related neuropathology characterized by severe neuronal loss and gliosis in CA1 and/or subiculum, is found in ∼80% of cases that are positive for phosphorylated TDP-43. HS-A is seen as a co-pathology in cases with AD, limbic-predominant age-related TDP-43 encephalopathy neuropathologic changes (LATE-NC), and frontotemporal degeneration.

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Manganese superoxide dismutase (MnSOD/SOD2) is an essential mitochondrial enzyme that detoxifies superoxide radicals generated during oxidative respiration. MnSOD/SOD2 lysine 68 acetylation (K68-Ac) is an important post-translational modification (PTM) that regulates enzymatic activity, responding to nutrient status or oxidative stress, and elevated levels have been associated with human illness. To determine the in vivo role of MnSOD-K68 in the heart, we used a whole-body non-acetylation mimic mutant (MnSOD) knock-in mouse.

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Objective: No published methods for research integrity review include both statistical techniques applied to groups of randomised trials and individual assessment of papers. We propose a method based on practical experience of investigating data integrity across the collected papers of one author or author-group.

Study Design And Setting: We report our approach to investigating the collected papers of an author or author-group suspected of academic misconduct.

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: In this study we analyzed the perceived effectiveness of cannabidiol (CBD) in adult women with inflammatory bowel disease (IBD). : We conducted an online cross-sectional survey which assessed disease severity and quality of life (QOL) in women with IBD (Crohn's disease and ulcerative colitis) who used CBD versus those who did not. The survey included: the Harvey-Bradshaw Index, Partial Mayo Score, Short Inflammatory Bowel Disease Questionnaire, Bristol Stool Scale, and the Prime Screen Short Food Frequency Questionnaire.

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  • Menstrual issues in young people (YP) are often overlooked, leading to unmanaged conditions like dysmenorrhoea and heavy bleeding that significantly affect their quality of life, especially during adolescence.
  • The LongSTEPPP project is a 5-year study focused on understanding the factors contributing to endometriosis, period, and pelvic pain in YP, with the goal of examining long-term effects.
  • Focus groups were conducted to gather insights from YP and their parents, revealing themes around the impact of pain, pain management, and a general lack of knowledge about menstrual issues, highlighting the mental health challenges faced by YP.
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Background: Clinical guidelines rely on sound evidence to underpin recommendations for patient care. Compromised research integrity can erode public trust and the credibility of the scientific enterprise, with potential harm to patients. Despite increased recognition of integrity concerns in scientific literature, there are no processes or guidance for incorporating integrity assessments into evidence-based guideline development or evidence synthesis more broadly.

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To gain further insight into the conformational properties of small cyclic peptides that bind to the G-protein coupled receptor C5aR1, we report here for the first time the elucidation of three peptide solution conformations using residual dipolar couplings and NMR temperature coefficients. Each of these peptides varies by at least one amino acid, adopts a different intramolecular hydrogen bonding pattern, and has a different solution conformation. The solution conformations were used in combination with a homology structure of C5aR1 as a design template for increasing the potency of peptide leads for the C5a receptor.

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Objective: Compare the effectiveness of instructional videos with print handouts when educating family medicine patients about the use of herbs and spices to reduce sodium, saturated fat, and added sugars during meal preparation.

Design: Enrollees were randomized to either view 5 short videos or read 3 handouts. The intervention was implemented while patients waited for their provider to begin their appointment.

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  • The study investigates the use of guideline-directed medical therapy (GDMT) in patients who survive cardiogenic shock (CS) with heart failure and reduced left ventricular ejection fraction (HFrEF) based on data from a single-center shock registry.
  • Among 520 patients treated for CS, 185 (35.6%) had HFrEF upon discharge, with a median age of 64 years; 41% experienced shock due to acute myocardial infarction, while the rest had heart failure-related shock.
  • At discharge, a substantial portion of patients were prescribed GDMT, including beta-blockers (78%), ACE inhibitors/ARBs (58%), and mineralocorticoid receptor antagonists (55%), yet 10
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  • The 2024 Australian evidence-based guideline offers recommendations for diagnosing and treating unexplained infertility in couples, tailored specifically for the Australian healthcare context and approved by national health authorities.
  • The guideline contains 40 evidence-based recommendations, addressing areas such as defining infertility, diagnosing various factors contributing to infertility, and treatment options, with a focus on improving patient care.
  • Key updates include a refined definition of unexplained infertility and a more comprehensive assessment process, integrating considerations of evidence quality, safety, and practicality for implementing these guidelines in Australia.
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Progression of acute traumatic brain injury (TBI) into chronic neurodegeneration is a major health problem with no protective treatments. Here, we report that acutely elevated mitochondrial fission after TBI in mice triggers chronic neurodegeneration persisting 17 months later, equivalent to many human decades. We show that increased mitochondrial fission after mouse TBI is related to increased brain levels of mitochondrial fission 1 protein (Fis1) and that brain Fis1 is also elevated in human TBI.

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Menopause is an inevitable physiologic process that typically occurs in women between the ages of 45 and 56 years old. It involves the permanent cessation of ovarian function and is recognized to have occurred when there has been no menstrual cycle for 12 consecutive months without another cause. Vasomotor symptoms, such as hot flushes and night sweats, and genitourinary syndrome of menopause, which includes symptoms of vaginal dryness, dyspareunia, and urinary incontinence, are common symptoms of menopause.

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  • The study examines the transcriptional and epigenomic changes in the human cerebellum related to Alzheimer's disease (AD) and AD-related dementias, evaluating 103,861 nuclei from AD cases and controls through advanced genome analysis techniques.
  • Researchers identified thousands of significant connections between gene expression and chromatin accessibility, focusing on key transcription factors RORA and ELF1 in specific cerebellar cell types, which correlate with disease-specific changes.
  • The analysis also highlighted two potentially crucial genes, SEZ6L2 and KANSL1, that may play a role in the pathology of AD, providing new insights into the genetic and epigenetic factors influencing neurological disorders.
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Despite numerous neuropathological criteria for the evaluation of microscopic tissue slides, there are no systemic standards for sectioning postmortem human brain tissue. Here, we present a protocol for postmortem brain hybrid structured-light scanning to facilitate 3D printing of sectioning matrices. We describe steps for tissue preparation, 3D scanning and printing, and matrix-guided sectioning.

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  • * Many patients continue to experience severe symptoms and face risks such as rehospitalization and increased mortality despite advancements in medication.
  • * Recent years have seen growth in innovative device-based therapies for HF, addressing these gaps and showing effectiveness in managing the condition across various patient profiles.
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Sclerosing stromal tumors are a rare type of ovarian tumor in the category of sex cord stromal tumors, which arise from the ovarian connective tissue. This report concerns a case of a sclerosing stromal tumor in a 19-year-old nulliparous woman who presented with the chief complaints of menstrual irregularities and dyspareunia. Preoperative imaging revealed a complex right adnexal mass with blood flow and without associated ascites.

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Limited studies have examined the extent to which cyberbullying and offline bullying are factors related to youth admissions to behavioral health inpatient units. However, considering the rising use of technology and prevalence of youth bullying, intake procedures require adaptation to account for modern-day psychological pressures facing youth. : Our aims were to pilot and analyze results from a novel intake form, assessing offline bullying and cyberbullying, in a youth inpatient behavioral health facility.

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Background: Electronic health records (EHRs) can accelerate documentation and may enhance details of notes, or complicate documentation and introduce errors. Comprehensive assessment of documentation quality requires comparing documentation to what transpires during the clinical encounter itself. We assessed outpatient primary care notes and corresponding recorded encounters to determine accuracy, thoroughness, and several additional key measures of documentation quality.

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Six hundred and fifty-four inpatients who participated in a spiritual group therapy intervention provided qualitative feedback regarding what helped them and what could be improved. Patients revealed that enjoying a sense of connection with other people and a sense of openness in the groups and simply talking about spirituality with other people was helpful to them. Many group members requested that groups go on for a longer amount of time than 12 sessions, to have longer sessions, and to have more frequent meetings.

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Frontotemporal lobar degeneration with neuronal inclusions of the TAR DNA-binding protein 43 (FTLD-TDP) is a fatal neurodegenerative disorder with only a limited number of risk loci identified. We report our comprehensive genome-wide association study as part of the International FTLD-TDP Whole-Genome Sequencing Consortium, including 985 cases and 3,153 controls, and meta-analysis with the Dementia-seq cohort, compiled from 26 institutions/brain banks in the United States, Europe and Australia. We confirm as the strongest overall FTLD-TDP risk factor and identify as a novel FTLD-TDP risk factor.

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  • Postmenopausal cardiovascular health is crucial for longevity, and beetroot juice (BR), which is rich in nitrates, can enhance nitric oxide levels, benefiting endothelial function.
  • Research compared the effects of a single dose of nitrate-rich beetroot juice on early-postmenopausal women to late-postmenopausal women, finding different improvements in endothelial function and resistance to ischemia-reperfusion (IR) injury.
  • The study showed that while beetroot juice significantly improved macrovascular function in late-postmenopausal women, early-postmenopausal women had a stronger overall response, indicating that menopause timing may influence how dietary nitrates affect cardiovascular health.
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