Publications by authors named "Mackenzie Scott"

Article Synopsis
  • The lipid kinase PI4KIIIα is crucial for maintaining the lipid makeup of cell membranes and operates in a complex with regulatory proteins TTC7 and FAM126.
  • Cryogenic electron microscopy revealed how the EFR3A protein binds to this complex, causing a change in its structure and facilitating interactions with TTC7 and FAM126.
  • Mutations that disrupt these interactions can hinder PI4KA's recruitment to the membrane, highlighting potential links between posttranslational modifications or mutations and human diseases.
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Introduction: Chronic pelvic pain affects up to 24% of women worldwide and for up to 55% of these there is no associated pathology. Despite this there are no established treatments in this cohort. This is a secondary analysis of a randomised-controlled trial (GaPP2) to explore if there are measures which enable us to predict treatment outcome.

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  • - Colorectal cancer is common worldwide, and micropapillary carcinoma (MPC) is a subtype linked to poorer outcomes, though it's not well recognized in colorectal cases.
  • - The study reviewed 597 colorectal cancer surgeries in Sydney from 2019 to 2024, finding MPC in 21 cases (3.5%), with a mean patient age of 60.
  • - MPC tumors often showed advanced stages, high lymph node involvement, and significant lymphovascular invasion, leading to 1-year survival rates of 90% and 3-year rates of 76%, indicating the need for better diagnosis and treatment strategies.
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  • Chronic pelvic pain (CPP) in women without clear pelvic issues lacks effective treatment options, as shown by a recent trial indicating gabapentin was ineffective and had more side effects compared to a placebo.
  • An exploratory study identified a significant genetic variant (rs4442490) linked to the response to gabapentin, suggesting this variant may influence how patients experience pain relief from the medication.
  • The genetic variant rs4442490 affects the expression of Neuregulin 3, which is important for brain function, particularly the orbitofrontal cortex, highlighting the potential for personalized treatment based on genetic factors.
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  • Male factor infertility affects up to 50% of couples struggling to conceive, prompting research into non-hormonal treatments to enhance sperm production.
  • This study aimed to evaluate the effectiveness of various non-hormonal pharmacological treatments through a systematic review and network meta-analysis of randomized trials.
  • Results showed that clomiphene citrate significantly improved sperm concentration compared to other treatments and was deemed the most effective option among them, although the overall quality of the trials was low.
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  • The study compares two methods, immunohistochemistry (IHC) and droplet digital PCR (ddPCR), for detecting microsatellite instability (MSI) in colorectal cancer (CRC) patients and finds high agreement between the two techniques.
  • Analysis reveals that patients with MSI-high have better overall and disease-free survival compared to those with microsatellite stability (MSS), particularly in right-sided CRC cases.
  • The research suggests that ddPCR is a valuable tool for MSI detection and highlights the differing impacts of MSI-high and loss of MLH1 expression on patient outcomes in CRC, indicating that both methods can be useful for prognostic assessments.
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The lipid kinase phosphatidylinositol 4 kinase III alpha (PI4KIIIa/PI4KA) is a master regulator of the lipid composition and asymmetry of the plasma membrane. PI4KA exists primarily in a heterotrimeric complex with its regulatory proteins TTC7 and FAM126. Fundamental to PI4KA activity is its targeted recruitment to the plasma membrane by the lipidated proteins EFR3A and EFR3B.

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Aims: Ramadan-focused diabetes education is critical to facilitate safer Ramadan fasting amongst Muslim people living with diabetes. We present the design, delivery, and evaluation of two parallel massive open online courses (MOOCs) in Ramadan-focused diabetes education for people with diabetes and HCPs.

Methods: Two Ramadan-focused diabetes education MOOCs were developed and delivered for Ramadan 2023: one for HCPs in English, and another for people with diabetes in English, Arabic and Malay.

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Aldosterone is a cardiovascular hormone with a key role in blood pressure regulation, among other processes, mediated through its targeting of the mineralocorticoid receptor in the renal tubule and selected other tissues. Its secretion from the adrenal gland is a highly controlled process subject to regulatory influence from the renin-angiotensin system and the hypothalamic-pituitary-adrenal axis. MicroRNAs are small endogenous non-coding RNA molecules capable of regulating gene expression post-transcriptionally through stimulation of mRNA degradation or suppression of translation.

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The cell cycle plays a key and complex role in the development of human cancers. p21 is a potent cyclin-dependent kinase inhibitor (CDKI) involved in the promotion of cell cycle arrest and the regulation of cellular senescence. Altered p21 expression in rectal cancer cells may affect tumor cells' behavior and resistance to neoadjuvant and adjuvant therapy.

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Background: Crohn's disease patients may require multiple surgeries during their lifetime. Because operative reports are not standardized, information relevant to future management may not be documented. Synoptic reports used in other fields such as histopathology have proven to be effective and allow consistent documentation of results.

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and mutation rates in colorectal cancer (CRC) reported from various mono-ethnic studies vary amongst different ethnic groups. However, these differences in mutation rates may not be statistically significant or may be due to differences in environmental and/or laboratory factors across countries rather than racial genetic differences. Here, we compare the / mutation rates and survival outcomes in CRC between ethnic groups at a single institution.

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Article Synopsis
  • Diabetes specialists mostly focus on type 1 diabetes technology like glucose sensors and insulin pumps, but there’s a lot more to explore with AI for all types of diabetes.
  • AI can help improve patient education, support doctors’ decisions, and use different types of data for better care.
  • It’s important for everyone involved, like doctors and patients, to work together to make sure we can use AI safely and avoid problems like unequal access to care.
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Laboratory testing has been a key tool in managing the SARS-CoV-2 global pandemic. While rapid antigen and PCR testing has proven useful for diagnosing acute SARS-CoV-2 infections, additional testing methods are required to understand the long-term impact of SARS-CoV-2 infections on immune response. Serological testing, a well-documented laboratory practice, measures the presence of antibodies in a sample to uncover information about host immunity.

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  • Next generation sequencing (NGS) helps identify actionable mutations in metastatic colorectal cancer (CRC) patients, with a focus on different mutation tiers based on the European Society of Medical Oncology (ESMO) Scale.
  • A study of 180 CRC tissue samples revealed that 82% had mutations, including Tier I variants like RAS wild-type and BRAF V600E, and found that concurrent mutations were common, impacting survival outcomes.
  • Notably, patients with TP53 and RAS mutations had shorter survivals, and high KRAS allele frequency correlated with reduced overall survival, indicating the importance of genomic profiling in treatment decisions.
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Background: Time is a valuable commodity that impacts hospital flow, patient experience and economic resources. This study aims to identify factors that affect daily treatment time over a course of radiation therapy (RT) in patients who underwent adjuvant breast RT.

Methods: In all adjuvant breast/chestwall RT patients treated from October 2017 to May 2018, daily set-up, beam delivery time, and overall treatment times were collected.

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The GENCOV study aims to identify patient factors which affect COVID-19 severity and outcomes. Here, we aimed to evaluate patient characteristics, acute symptoms and their persistence, and associations with hospitalization. Participants were recruited at hospital sites across the Greater Toronto Area in Ontario, Canada.

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Background: Endometriosis affects 190 million women and those assigned female at birth worldwide. For some, it is associated with debilitating chronic pelvic pain. Diagnosis of endometriosis is often achieved through diagnostic laparoscopy.

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An ectopic pregnancy occurs when an embryo implants outside of the uterus, usually in a fallopian tube. When detected early, treatment is often with a medication called methotrexate. When methotrexate does not work, surgery is required.

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Study Question: What is the capacity of the change between Day 1 and Day 4 post-treatment serum human chorionic gonadotropin (hCG) levels for predicting single-dose methotrexate treatment success in tubal ectopic pregnancy?

Summary Answer: Any fall in Days 1-4 serum hCG signified an 85% (95% CI 76.8-90.6) likelihood of treatment success for women with tubal ectopic pregnancy (initial hCG of ≥1000 and ≤5000 IU/l) managed with single-dose methotrexate.

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Study Question: What is the risk of miscarriage among pregnant women who received any of the COVID-19 vaccines?

Summary Answer: There is no evidence that COVID-19 vaccines are associated with an increased risk of miscarriage.

What Is Known Already: In response to the COVID-19 pandemic, the mass roll-out of vaccines helped to boost herd immunity and reduced hospital admissions, morbidity, and mortality. Still, many were concerned about the safety of vaccines for pregnancy, which may have limited their uptake among pregnant women and those planning a pregnancy.

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The formation of complexes between Rab11 and its effectors regulates multiple aspects of membrane trafficking, including recycling and ciliogenesis. WD repeat-containing protein 44 (WDR44) is a structurally uncharacterized Rab11 effector that regulates ciliogenesis by competing with prociliogenesis factors for Rab11 binding. Here, we present a detailed biochemical and biophysical characterization of the WDR44-Rab11 complex and define specific residues mediating binding.

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Article Synopsis
  • Arterial hypertension is a major global health issue and can be either primary or secondary, with secondary cases linked to specific endocrine disorders like Cushing's syndrome, primary aldosteronism, and pheochromocytoma.
  • Effective diagnosis of endocrine hypertension relies on hormone tests, but identifying unique blood DNA methylation patterns could enhance diagnosis and treatment strategies.
  • The study examined DNA methylation patterns in 255 patients, successfully distinguishing between primary and secondary hypertension using machine learning techniques, with varying levels of accuracy in predictive models.
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Background: Arterial hypertension is a major cardiovascular risk factor. Identification of secondary hypertension in its various forms is key to preventing and targeting treatment of cardiovascular complications. Simplified diagnostic tests are urgently required to distinguish primary and secondary hypertension to address the current underdiagnosis of the latter.

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