Medicine and Health Sciences Commons^™

Abcb5+ Mesenchymal Stromal Cells Therapy Protects From Hypoxia By Restoring Ca2+ Homeostasis In Vitro And In Vivo, Kaixuan Yan, Jiaxing Zheng, Mark Andreas Kluth, Lin Li, Christoph Ganss, Benito Yard, Richard Magdeburg, Markus H. Frank, Prama Pallavi, Michael Keese

Research outputs 2022 to 2026

Background:

Hypoxia in ischemic disease impairs Ca²⁺ homeostasis and may promote angiogenesis. The therapeutic efficacy of mesenchymal stromal cells (MSCs) in peripheral arterial occlusive disease is well established, yet its influence on cellular Ca²⁺ homeostasis remains to be elucidated. We addressed the influence of ATP-binding cassette subfamily B member 5 positive mesenchymal stromal cells (ABCB5⁺ MSCs) on Ca²⁺ homeostasis in hypoxic human umbilical vein endothelial cells (HUVECs) in vitro and in vivo.

Methods:

Hypoxia was induced in HUVECs by Cobalt (II) chloride (CoCl₂) or Deferoxamine (DFO). Dynamic changes in the cytosolic- and endoplasmic reticulum …

Examining Dose Frameworks To Improve Aphasia Rehabilitation Research, Sam Harvey, Miranda L. Rose, Emily Brogan, John E. Pierce, Erin Godecke, Sonia L. E. Brownsett, Leonid Churilov, David Copland, Michael Walsh Dickey, Jade Dignam, Natasha A. Lannin, Lyndsey Nickels, Julie Bernhardt, Kathryn S. Hayward

Research outputs 2022 to 2026

The effect of treatment dose on recovery of post-stroke aphasia is not well understood. Inconsistent conceptualization, measurement, and reporting of the multiple dimensions of dose hinders efforts to evaluate dose-response relations in aphasia rehabilitation research. We review the state of dose conceptualization in aphasia rehabilitation and compare the applicability of 3 existing dose frameworks to aphasia rehabilitation research—the Frequency, Intensity, Time, and Type (FITT) principle, the Cumulative Intervention Intensity (CII) framework, and the Multidimensional Dose Articulation Framework (MDAF). The MDAF specifies dose in greater detail than the CII framework and the FITT principle. On this basis, we selected the MDAF …

Human Pluripotent Stem Cell-Derived Β Cells: Truly Immature Islet Β Cells For Type 1 Diabetes Therapy?, Helen Jiang, Fang-Xu Jiang

Research outputs 2022 to 2026

A century has passed since the Nobel Prize winning discovery of insulin, which still remains the mainstay treatment for type 1 diabetes mellitus (T1DM) to this day. True to the words of its discoverer Sir Frederick Banting, “insulin is not a cure for diabetes, it is a treatment”, millions of people with T1DM are dependent on daily insulin medications for life. Clinical donor islet transplantation has proven that T1DM is curable, however due to profound shortages of donor islets, it is not a mainstream treatment option for T1DM. Human pluripotent stem cell derived insulin-secreting cells, pervasively known as stem cell-derived …

The Perth Alexithymia Questionnaire-Short Form (Paq-S): A 6-Item Measure Of Alexithymia, David A. Preece, Ashish Mehta, Kate Petrova, Pilleriin Sikka, Johan Bjureberg, Wai Chen, Rodrigo Becerra, Alfred Allan, Ken Robinson, James J. Gross

Research outputs 2022 to 2026

Background: Alexithymia is a trait characterized by difficulties identifying feelings, difficulties describing feelings, and externally orientated thinking. It is widely regarded as an important transdiagnostic risk factor for a range of psychopathologies, including depressive and anxiety disorders. Whilst several well-validated psychometric measures of alexithymia exist, these are relatively lengthy, thus limiting their utility in time-pressured settings. In this paper, we address this gap by introducing and validating a brief 6-item version of the Perth Alexithymia Questionnaire, called the Perth Alexithymia Questionnaire-Short Form (PAQ-S). Method: Across two studies with adult samples (Study 1 N = 508 United States community; Study 2 …

Tweak/Fn14 Signalling Regulates The Tissue Microenvironment In Chronic Pancreatitis, N. Dianah B. Abu Bakar, Rodrigo Carlessi, Jully Gogoi-Tiwari, Julia Köhn-Gaone, Vincent Williams, Marco Falasca, John K. Olynyk, Grant A. Ramm, Janina E. E. Tirnitz-Parker

Research outputs 2022 to 2026

Chronic pancreatitis increases the risk of developing pancreatic cancer through the upregulation of pathways favouring proliferation, fibrosis, and sustained inflammation. We established in previous studies that the ligand tumour necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK) signals through its cognate receptor fibroblast growth factor-inducible 14 (Fn14) to regulate these underlying cellular processes in the chronic liver injury niche. However, the role of the TWEAK/Fn14 signalling pathway in pancreatic disease is entirely unknown. An analysis of publicly available datasets demonstrated that the TWEAK receptor Fn14 is upregulated in pancreatitis and pancreatic adenocarcinoma, with single cell RNA sequencing revealing pancreatic ductal …

Rapid Prediction Of Multidrug-Resistant Klebsiella Pneumoniae Through Deep Learning Analysis Of Sers Spectra, Jing-Wen Lyu, Xue Di Zhang, Jia-Wei Tang, Yun-Hu Zhao, Su-Ling Liu, Yue Zhao, Ni Zhang, Dan Wang, Long Ye, Xiao-Li Chen, Liang Wang, Bing Gu

Research outputs 2022 to 2026

Klebsiella pneumoniae is listed by the WHO as a priority pathogen of extreme importance that can cause serious consequences in clinical settings. Due to its increasing multidrug resistance all over the world, K. pneumoniae has the potential to cause extremely difficult-To-Treat infections. Therefore, rapid and accurate identification of multidrug-resistant K. pneumoniae in clinical diagnosis is important for its prevention and infection control. However, the limitations of conventional and molecular methods significantly hindered the timely diagnosis of the pathogen. As a label-free, noninvasive, and low-cost method, surface-enhanced Raman scattering (SERS) spectroscopy has been extensively studied for its application potentials in the …

Epigenetic Regulation Of Corneal Epithelial Differentiation By Tet2, Yuzuru Sasamoto, Siyuan Wu, Catherine A. A. Lee, Jason Y. Jiang, Bruce R. Ksander, Markus H. Frank, Natasha Y. Frank

Research outputs 2022 to 2026

Epigenetic DNA modification by 5-hydroxymethylcytosine (5hmC), generated by the Ten-eleven translocation (TET) dioxygenases, regulates diverse biological functions in many organ tissues, including the mammalian eye. For example, 5hmC has been shown to be involved in epigenetic regulation of retinal gene expression. However, a functional role of 5hmC in corneal differentiation has not been investigated to date. Here, we examined 5hmC and TET function in the human cornea. We found 5hmC highly expressed in MUC16-positive terminally differentiated cells that also co-expressed the 5hmC-generating enzyme TET2. TET2 knockdown (KD) in cultured corneal epithelial cells led to significant reductions of 5hmC peak distributions …

Acceptability, Feasibility And Preliminary Efficacy Of Low-Moderate Intensity Constraint Induced Aphasia Therapy And Multi-Modality Aphasia Therapy In Chronic Aphasia After Stroke, John E. E. Pierce, Robyn Ohalloran, Leanne Togher, Lyndsey Nickels, David Copland, Erin Godecke, Marcus Meinzer, Tapan Rai, Dominique A. Cadilhac, Joosup Kim, Melanie Hurley, Abby Foster, Marcella Carragher, Cassie Wilcox, Gillian Steel, Miranda L. Rose

Research outputs 2022 to 2026

Background: High-intensity Constraint-Induced Aphasia Therapy Plus (CIAT-Plus) and Multi-Modality Aphasia Therapy (M-MAT) are effective interventions for chronic post-stroke aphasia but challenging to provide in clinical practice. Providing these interventions may be more feasible at lower intensities, but comparative evidence is lacking. We therefore explored feasibility, acceptability, and preliminary efficacy of the treatments at a lower intensity. Methods: A multisite, single-blinded, randomized Phase II trial was conducted within the Phase III COMPARE trial. Groups of participants with chronic aphasia from the usual care arm of the COMPARE trial were randomized to M-MAT or CIAT-Plus, delivered at the same dose as the …

An Updated Systematic Review Of Stroke Clinical Practice Guidelines To Inform Aphasia Management, Bridget Burton, Megan Isaacs, Emily Brogan, Kirstine Shrubsole, Monique F. Kilkenny, Emma Power, Erin Godecke, Dominique A. Cadilhac, David Copland, Sarah J. Wallace

Research outputs 2022 to 2026

Background: Aphasia is a common consequence of stroke, and people who live with this condition experience poor outcomes. Adherence to clinical practice guidelines can promote high-quality service delivery and optimize patient outcomes. However, there are currently no high-quality guidelines specific to post-stroke aphasia management. Aims: To identify and evaluate recommendations from high-quality stroke guidelines that can inform aphasia management. Summary of review: We conducted an updated systematic review in accordance with PRISMA guidelines to identify high-quality clinical guidelines published between January 2015 and October 2022. Primary searches were performed using electronic databases: PubMed, EMBASE, CINAHL, and Web of Science. Gray …

Locally Performed Postoperative Circulating Tumour Dna Testing Performed During Routine Clinical Care To Predict Recurrence Of Colorectal Cancer, Ryan Cohen, Aaron Beasley, Melanie Mccoy, Cameron Platell, Katie Meehan, Elin Gray, Kathy Fuller

Research outputs 2022 to 2026

Background: Identifying patients at high risk for colorectal cancer recurrence is essential for improving prognosis. In the postoperative period, circulating tumour DNA (ctDNA) has been demonstrated as a significant prognostic indicator of recurrence. These results have been obtained under the strict rigours of clinical trials, but not validated in a real-world setting using in-house testing. We report the outcomes of locally performed postoperative ctDNA testing conducted during routine clinical care and the association with the recurrence of colorectal cancer. Methods: We recruited 36 consecutive patients with newly diagnosed colorectal cancer between 2018 and 2020. Postoperative plasma samples were collected at …

Leukocyte Surface Biomarkers Implicate Deficits Of Innate Immunity In Sporadic Alzheimer's Disease, Xin Huang, Yihan Li, Christopher Fowler, James D. Doecke, Yen Ying Lim, Candace Drysdale, Vicky Zhang, Keunha Park, Brett Trounson, Kelly Pertile, Rebecca Rumble, John W. Pickering, Robert A. Rissman, Floyd Sarsoza, Sara Abdel-Latif, Yong Lin, Vincent Doré, Victor Villemagne, Christopher C. Rowe, Jurgen Fripp, Ralph Martins, James S. Wiley, Paul Maruff, Jacobo E. Mintzer, Colin L. Masters, Ben J. Gu

Research outputs 2022 to 2026

Introduction:

Blood-based diagnostics and prognostics in sporadic Alzheimer's disease (AD) are important for identifying at-risk individuals for therapeutic interventions.

Methods:

In three stages, a total of 34 leukocyte antigens were examined by flow cytometry immunophenotyping. Data were analyzed by logistic regression and receiver operating characteristic (ROC) analyses.

Results:

We identified leukocyte markers differentially expressed in the patients with AD. Pathway analysis revealed a complex network involving upregulation of complement inhibition and downregulation of cargo receptor activity and Aβ clearance. A proposed panel including four leukocyte markers – CD11c, CD59, CD91, and CD163 – predicts patients’ PET Aβ status with an …