Reclaiming Agency in Care Decisions and Barriers From the Perspectives of Individuals With Acquired Brain Injury and Their Family Members.

Background: The ability to self-advocate or have a say in one's care is integral to personalised care after acquired brain injury (ABI). This study aimed to understand what constitutes self-advocacy and associated barriers and facilitators throughout hospital transitions and into the community.

Method: Qualitative methodology was employed with semistructured interviews conducted with 12 people with ABI and 13 family members.

The typing is on the wall: Australia's healthcare future needs a digitally capable workforce.

Digital health technologies are a proposed solution to improve healthcare delivery and reduce pressures on the healthcare system, but these technologies are new to much of the health workforce. This perspective paper highlights lessons learned from the global experience of rapid digital transformation of health workforces, including fostering a culture of learning, ensuring accreditation and recognition, and adopting a transdisciplinary approach. Evidence-based actions are proposed to address recommendations to (1) ensure foundational workforce digital health capability and (2) build specialist digital health career pathways.

Immunodeficient patient experience of emergency switch from intravenous to rapid push subcutaneous immunoglobulin replacement therapy during coronavirus disease 2019 shielding.

Purpose Of Review: Welsh immunodeficient patients on immunoglobulin replacement therapy (IgRT) who were considered high risk for severe coronavirus disease 2019 (COVID-19) were directed to shield. Consequently, patients receiving hospital-based intravenous immunoglobulin (IVIg) quickly transitioned to home-based self-administered subcutaneous immunoglobulin (SCIg). This evaluation aimed to assess patients' perceptions and experiences and laboratory outcomes of emergency IgRT transition during COVID-19.

BRCA mutations lead to XIAP overexpression and sensitise ovarian cancer to inhibitor of apoptosis (IAP) family inhibitors.

Background: We tested the hypothesis that inhibitor of apoptosis family (IAP) proteins may be altered in BRCA1-mutated ovarian cancers and that could affect the sensitivity to IAP inhibitors.

Methods: The levels of IAP proteins were evaluated in human cancers and cell lines. Cell lines were used to determine the effects of IAP inhibitors.

Targeting the PI3K and MAPK pathways to improve response to HER2-targeted therapies in HER2-positive gastric cancer.

Background: Aberrant PI3K signalling is implicated in trastuzumab resistance in HER2-positive gastric cancer (GC). The role of PI3K or MEK inhibitors in sensitising HER2-positive GCs to trastuzumab or in overcoming trastuzumab resistance is unclear.

Methods: Using mass spectrometry-based genotyping we analysed 105 hotspot, non-synonymous somatic mutations in PIK3CA and ERBB-family (EGFR, ERBB2, ERBB3 and ERBB4) genes in gastric tumour samples from 69 patients.

Identification and clinical impact of potentially actionable somatic oncogenic mutations in solid tumor samples.

Background: An increasing number of anti-cancer therapeutic agents target specific mutant proteins that are expressed by many different tumor types. Successful use of these therapies is dependent on the presence or absence of somatic mutations within the patient's tumor that can confer clinical efficacy or drug resistance.

Methods: The aim of our study was to determine the type, frequency, overlap and functional proteomic effects of potentially targetable recurrent somatic hotspot mutations in 47 cancer-related genes in multiple disease sites that could be potential therapeutic targets using currently available agents or agents in clinical development.

Combined targeting EGFR and SRC as a potential novel therapeutic approach for the treatment of triple negative breast cancer.

Background: Triple negative breast cancer (TNBC) is an aggressive subtype of breast cancer with limited therapeutic options. Epidermal growth factor receptor (EGFR) has been shown to be over-expressed in TNBC and represents a rational treatment target.

Methods: We examined single agent and combination effects for afatinib and dasatinib in TNBC.

Haemopedia RNA-seq: a database of gene expression during haematopoiesis in mice and humans.

During haematopoiesis, haematopoietic stem cells differentiate into restricted potential progenitors before maturing into the many lineages required for oxygen transport, wound healing and immune response. We have updated Haemopedia, a database of gene-expression profiles from a broad spectrum of haematopoietic cells, to include RNA-seq gene-expression data from both mice and humans. The Haemopedia RNA-seq data set covers a wide range of lineages and progenitors, with 57 mouse blood cell types (flow sorted populations from healthy mice) and 12 human blood cell types.

Frequency, impact and a preclinical study of novel gene family mutations in HER2-positive breast cancer.

Background: Somatic mutations in the genes (epidermal growth factor receptor: ) promote oncogenesis and lapatinib resistance in metastatic HER2+ (human epidermal growth factor-like receptor 2) breast cancer . Our study aimed to determine the frequency of mutations in four genes: and and to investigate whether these mutations affect cellular behaviour and therapy response and outcomes after adjuvant trastuzumab-based therapy in clinical samples.

Methods: We performed Agena MassArray analysis of 227 HER2+ breast cancer samples to identify the type and frequency of family mutations.

Preclinical evaluation and reverse phase protein Array-based profiling of PI3K and MEK inhibitors in endometrial carcinoma in vitro.

Background: The phosphoinositide-3-kinase (PI3K) pathway is the most commonly activated pathway in cancers due to mutations at multiple nodes and loss of PTEN. Furthermore, in endometrial cancer (EC), PI3K and RAS/RAF/MEK/MAPK (RAS/MAPK herein) pathway mutations frequently co-exist. We examined the role of PI3K and RAS/MAPK pathway mutations in determining responsiveness to therapies targeted to these pathways in vitro in EC.

A preclinical evaluation of the MEK inhibitor refametinib in HER2-positive breast cancer cell lines including those with acquired resistance to trastuzumab or lapatinib.

Purpose: The MEK/MAPK pathway is commonly activated in HER2-positive breast cancer, but little investigation of targeting this pathway has been undertaken. Here we present the results of an preclinical evaluation of refametinib, an allosteric MEK1/2 inhibitor, in HER2-positive breast cancer cell lines including models of acquired resistance to trastuzumab or lapatinib.

Methods: A panel of HER2-positive breast cancer cells were profiled for mutational status and also for anti-proliferative response to refametinib alone and in combination with the PI3K inhibitor (PI3Ki) copanlisib and the HER2-targeted therapies trastuzumab and lapatinib.

BCL-2 system analysis identifies high-risk colorectal cancer patients.

Objective: The mitochondrial apoptosis pathway is controlled by an interaction of multiple BCL-2 family proteins, and plays a key role in tumour progression and therapy responses. We assessed the prognostic potential of an experimentally validated, mathematical model of BCL-2 protein interactions (DR_MOMP) in patients with stage III colorectal cancer (CRC).

Design: Absolute protein levels of BCL-2 family proteins were determined in primary CRC tumours collected from n=128 resected and chemotherapy-treated patients with stage III CRC.

A Stepwise Integrated Approach to Personalized Risk Predictions in Stage III Colorectal Cancer.

Apoptosis is essential for chemotherapy responses. In this discovery and validation study, we evaluated the suitability of a mathematical model of apoptosis execution (APOPTO-CELL) as a stand-alone signature and as a constituent of further refined prognostic stratification tools. Apoptosis competency of primary tumor samples from patients with stage III colorectal cancer ( = 120) was calculated by APOPTO-CELL from measured protein concentrations of Procaspase-3, Procaspase-9, SMAC, and XIAP.

Haemopedia: An Expression Atlas of Murine Hematopoietic Cells.

Hematopoiesis is a multistage process involving the differentiation of stem and progenitor cells into distinct mature cell lineages. Here we present Haemopedia, an atlas of murine gene-expression data containing 54 hematopoietic cell types, covering all the mature lineages in hematopoiesis. We include rare cell populations such as eosinophils, mast cells, basophils, and megakaryocytes, and a broad collection of progenitor and stem cells.

Irisin exerts dual effects on browning and adipogenesis of human white adipocytes.

To better understand the role of irisin in humans, we examined the effects of irisin in human primary adipocytes and fresh human subcutaneous white adipose tissue (scWAT). Human primary adipocytes derived from 28 female donors' fresh scWAT were used to examine the effects of irisin on browning and mitochondrial respiration, and preadipocytes were used to examine the effects of irisin on adipogenesis and osteogenesis. Cultured fragments of scWAT and perirenal brown fat were used for investigating signal transduction pathways that mediate irisin's browning effect by Western blotting to detect phosphorylated forms of p38, ERK, and STAT3 as well as uncoupling protein 1 (UCP1).

Brown-Sequard syndrome produced by calcified herniated cervical disc and posterior vertebral osteophyte: Case report.

Brown-Sequard syndrome (BSS) produced by cervical disc disorders has rarely been seen clinically and only 50 cases have been reported in English literatures. However, most of which have resulted from acute disc herniation. Here, we report a case of BSS produced by calcified herniated C4-C5 disc and posterior vertebral osteophyte, in which decompression through anterior approach was performed.

Chiropractic care of a patient with neurogenic heterotopic ossification of the anterior longitudinal ligament after traumatic brain injury: a case report.

Objective: The purpose of this case report is to describe the use of chiropractic care for a patient with neurogenic heterotopic ossification of the anterior longitudinal ligament in the cervical spine and soft tissues of the right hip after a traumatic brain injury and right femur fracture.

Clinical Features: A 25-year-old military officer was referred to a hospital-based chiropractic clinic with complaints of pain and stiffness of the neck and back along with reduced respiratory excursions that began several months after a motor vehicle accident in which he had a traumatic brain injury. The patient had a fractured right femur from the accident, which had since been treated surgically, but had complications of heterotopic ossification in the soft tissues of the hip.

Viability, growth kinetics and stem cell markers of single and clustered cells in human intervertebral discs: implications for regenerative therapies.

Purpose: There is much interest in the development of a cellular therapy for the repair or regeneration of degenerate intervertebral discs (IVDs) utilising autologous cells, with some trials already underway. Clusters of cells are commonly found in degenerate IVDs and are formed via cell proliferation, possibly as a repair response. We investigated whether these clusters may be more suitable as a source of cells for biological repair than the single cells in the IVD.

Abnormal mucosal extracellular matrix deposition is associated with increased TGF-beta receptor-expressing mesenchymal cells in a mouse model of colitis.

Transforming growth factor-beta (TGF-beta) depresses mucosal inflammation and upregulates extracellular matrix (ECM) deposition. We analyzed TGF-beta receptors RI and RII as well as ECM components using the CD4(+) T-cell-transplanted SCID mouse model of colitis. The principal change in colitis was an increased proportion of TGF-beta RII(+) mucosal mesenchymal cells, predominantly alpha-smooth muscle actin (SMA)(+) myofibroblasts, co-expressing vimentin and basement membrane proteins, but not type I collagen.