The Clinical Utility of a 7-Gene Biosignature on Radiation Therapy Decision Making in Patients with Ductal Carcinoma In Situ Following Breast-Conserving Surgery: An Updated Analysis of the DCISionRT PREDICT Study.

Background: Breast-conserving surgery (BCS) followed by adjuvant radiotherapy (RT) is a standard treatment for ductal carcinoma in situ (DCIS). A low-risk patient subset that does not benefit from RT has not yet been clearly identified. The DCISionRT test provides a clinically validated decision score (DS), which is prognostic of 10-year in-breast recurrence rates (invasive and non-invasive) and is also predictive of RT benefit.

GPTs are GPTs: Labor market impact potential of LLMs.

Research is needed to estimate how jobs may be affected.

Deciphering the Exact Sequence of Endogenous Soluble B Cell Maturation Antigen and Unbiased Quantitation in Multiple Myeloma Patient Samples by LC-MS.

Background: B-cell maturation antigen is a pivotal therapeutic target for multiple myeloma (MM). Membrane-bound BCMA can be cleaved by γ-secretase and shed as soluble BCMA (sBCMA). sBCMA can act as a neutralizing sink to compete with drug, as well as serve as a diagnostic/prognostic biomarker for MM.

Correlation of In Vitro Kinetic Stability to Preclinical In Vivo Pharmacokinetics for a Panel of Anti-PD-1 Monoclonal Antibody Interleukin 21 Mutein Immunocytokines.

The development of therapeutic fusion protein drugs is often impeded by the unintended consequences that occur from fusing together domains from independent naturally occurring proteins, consequences such as altered biodistribution, tissue uptake, or rapid clearance and potential immunogenicity. For therapeutic fusion proteins containing globular domains, we hypothesized that aberrant in vivo behavior could be related to low kinetic stability of these domains leading to local unfolding and susceptibility to partial proteolysis and/or salvage and uptake. Herein we describe an assay to measure kinetic stability of therapeutic fusion proteins by way of their sensitivity to the protease thermolysin.

Bovine papular stomatitis virus as a vaccine vector for cattle.

Virus vectored vaccines are not available commercially for cattle even though compelling potential applications exist. Bovine papular stomatitis virus (BPSV), a highly prevalent parapoxvirus, causes self-limited oral lesions in cattle. Ability of virus to accommodate large amounts of foreign DNA, induce low level of antiviral immunity, and circulate and likely persist in cattle populations, make BPSV an attractive candidate viral vector.

GP perspectives on a psychiatry phone line in Western Australia's Great Southern region: implications for addressing rural GP workload.

Background: Mental illness is a public health challenge disproportionately affecting rural Australians. GPs provide most of the mental health care, and they report increasing levels of burnout and unsustainable workload in the context of increased patient complexity. This may be more salient in rural settings characterised by resource constraints.

Transcatheter Treatment of Native Aortic Valve Regurgitation: The North American Experience With a Novel Device.

Background: Transcatheter treatment of patients with native aortic valve regurgitation (AR) has been limited by anatomical factors. No transcatheter device has received U.S.

Characterising variability in youth mental health service populations: A detailed and scalable approach using digital technology.

Objective: This study utilised digital technology to assess the clinical needs of young people presenting for care at centres across Australia.

Method: 1490 young people (12-25 years) who presented to one of 11 services from four geographical locations (urban New South Wales, urban South Australia, regional New South Wales, and regional Queensland) completed a digital multidimensional assessment at initial presentation. Characteristics were compared between services and geographical locations.

Patterns of mental healthcare provision in rural areas: A demonstration study in Australia and Europe.

Introduction: Mental healthcare systems are primarily designed to urban populations. However, the specific characteristics of rural areas require specific strategies, resource allocation, and indicators which fit their local conditions. This planning process requires comparison with other rural areas.

Patterns of service provision in child and adolescent mental health care in Australia.

Standard description of local care provision is essential for evidence-informed planning. This study aimed to map and compare the availability and diversity of current mental health service provision for children and adolescents in Australia. We used a standardised service classification instrument, the Description and Evaluation of Services and DirectoriEs (DESDE) tool, to describe service availability in eight urban and two rural health districts in Australia.

Combined 70- and 80-gene signatures identify tumors with genomically luminal biology responsive to neoadjuvant endocrine therapy and are prognostic of 5-year outcome in early-stage breast cancer.

Background: As more patients with early-stage breast cancer receive neoadjuvant endocrine therapy (NET), there is a need for reliable biomarkers that can identify patients with HR+ HER2- tumors who are likely to benefit from NET. NBRST (NCT01479101) compared the prognostic value of the 70-gene risk classification and 80-gene molecular subtyping signatures with conventional pathological classification methods in response to neoadjuvant therapy. We evaluated the association of these signatures with clinical response and 5-year outcome of patients treated with NET.

Capillary Electrophoresis-Mass Spectrometry (CE-MS) by Sheath-Flow Nanospray Interface and Its Use in Biopharmaceutical Applications.

Both capillary electrophoresis (CE) and mass spectrometry (MS) technologies are powerful analytical tools that have been used extensively in the characterization of biologics in the biopharmaceutical industry. The direct coupling of CE with MS is an attractive approach, in that the high separation capability of CE and the ultrasensitive detection and accurate identification performance of MS can be combined to provide a powerful system for the analysis of complex analytes. In this chapter, we discuss the detailed procedure of carrying out CE-MS analysis using a nano sheath-flow interface and its applications including intact mass analysis of monoclonal antibodies and fusion proteins, and a biotransformation study of two Fc-FGF21 molecules in a single-dose pharmacokinetic mice study.

Histological findings of corneal tissue after failed phototherapeutic keratectomy in macular corneal dystrophy - a case report.

Background: Macular corneal dystrophy is a rare inherited disease of the cornea leading to deposits mainly in the stroma. Affected patients suffer from progressive loss of visual acuity which should be treated with penetrating keratoplasty. This is the first case report describing the clinical and histopathological findings of corneal tissue after failed phototherapeutic keratectomy (PTK) in a patient with macular corneal dystrophy.

Distinct Neoadjuvant Chemotherapy Response and 5-Year Outcome in Patients With Estrogen Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Breast Tumors That Reclassify as Basal-Type by the 80-Gene Signature.

Purpose: The 80-gene molecular subtyping signature (80-GS) reclassifies a proportion of immunohistochemistry (IHC)-defined luminal breast cancers (estrogen receptor-positive [ER+], human epidermal growth factor receptor 2-negative [HER2-]) as Basal-Type. We report the association of 80-GS reclassification with neoadjuvant treatment response and 5-year outcome in patients with breast cancer.

Methods: Neoadjuvant Breast Registry Symphony Trial (NBRST; NCT01479101) is an observational, prospective study that included 1,069 patients with early-stage breast cancer age 18-90 years who received neoadjuvant therapy.

Visualizing Spatial and Stoichiometric Barriers to Bispecific T-Cell Engager Efficacy.

Bispecific T-cell engager (BiTE) molecules are biologic T cell-directing immunotherapies. Blinatumomab is approved for treatment of B-cell malignancies, but BiTE molecule development in solid tumors has been more challenging. Here, we employed intravital imaging to characterize exposure and pharmacodynamic response of an anti-muCD3/anti-huEGFRvIII mouse surrogate BiTE molecule in EGFR variant III (EGFRvIII)-positive breast tumors implanted within immunocompetent mice.

Age-Independent Preoperative Chemosensitivity and 5-Year Outcome Determined by Combined 70- and 80-Gene Signature in a Prospective Trial in Early-Stage Breast Cancer.

Background: The Neoadjuvant Breast Symphony Trial (NBRST) demonstrated the 70-gene risk of distant recurrence signature, MammaPrint, and the 80-gene molecular subtyping signature, BluePrint, precisely determined preoperative pathological complete response (pCR) in breast cancer patients. We report 5-year follow-up results in addition to an exploratory analysis by age and menopausal status.

Methods: The observational, prospective NBRST (NCT01479101) included 954 early-stage breast cancer patients aged 18-90 years who received neoadjuvant chemotherapy and had clinical and genomic data available.

Computational Analysis of Cytokine Release Following Bispecific T-Cell Engager Therapy: Applications of a Logic-Based Model.

Bispecific T-cell engaging therapies harness the immune system to elicit an effective anticancer response. Modulating the immune activation avoiding potential adverse effects such as cytokine release syndrome (CRS) is a critical aspect to realizing the full potential of this therapy. The use of suitable exogenous intervention strategies to mitigate the CRS risk without compromising the antitumoral capability of bispecific antibody treatment is crucial.

A Comparison of Self-Referral and Referral via Primary Care Providers, through Two Similar Digital Mental Health Services in Western Australia.

Digital mental health services (DMHSs) deliver mental health information, assessment, and treatment, via the internet, telephone, or other digital channels. The current study compares two DMHSs operating in Western Australia (WA)-The Practitioner Online Referral System (PORTS) and MindSpot. Both provide telephone and online psychological services at no cost to patients or referrers.

The novel ORFV protein ORFV113 activates LPA-p38 signaling.

Viruses have evolved mechanisms to subvert critical cellular signaling pathways that regulate a wide range of cellular functions, including cell differentiation, proliferation and chemotaxis, and innate immune responses. Here, we describe a novel ORFV protein, ORFV113, that interacts with the G protein-coupled receptor Lysophosphatidic acid receptor 1 (LPA1). Consistent with its interaction with LPA1, ORFV113 enhances p38 kinase phosphorylation in ORFV infected cells in vitro and in vivo, and in cells transiently expressing ORFV113 or treated with soluble ORFV113.