Artificial Intelligence to Predict Chronic Kidney Disease Progression to Kidney Failure: A Narrative Review.

Chronic kidney disease is characterised by the progressive loss of kidney function. However, predicting who will progress to kidney failure is difficult. Artificial Intelligence, including Machine Learning, shows promise in this area.

Understanding barriers, enablers and motivational factors for Australian healthcare educators teaching university students on clinical placement using the validated Physician Teaching Motivation Questionnaire.

Background: In Australia, university clinical programs rely heavily on external healthcare professionals to provide a range of authentic clinical training and professional development opportunities for students. There is, however, a limited understanding of the factors that motivate these professionals to be educators and whether this varies across different healthcare disciplines within Australia. As the demand for clinical placements continues to increase, it is critical for the ongoing success of these programs that universities identify both the barriers associated with teaching and the benefits that enhance job satisfaction.

Targeting MCL1-driven anti-apoptotic pathways overcomes blast progression after hypomethylating agent failure in chronic myelomonocytic leukemia.

RAS pathway mutations, which are present in 30% of patients with chronic myelomonocytic leukemia (CMML) at diagnosis, confer a high risk of resistance to and progression after hypomethylating agent (HMA) therapy, the current standard of care for the disease. Here, using single-cell, multi-omics technologies, we seek to dissect the biological mechanisms underlying the initiation and progression of RAS pathway-mutated CMML. We identify that RAS pathway mutations induce transcriptional reprogramming of hematopoietic stem and progenitor cells (HSPCs) and downstream monocytic populations in response to cell-intrinsic and -extrinsic inflammatory signaling that also impair the functions of immune cells.

Allogeneic hematopoietic stem cell transplantation after mogamulizumab in T-cell lymphoma patients: a retrospective analysis.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an important therapy for patients with T-cell lymphomas, including cutaneous T-cell lymphoma (CTCL), adult T-cell lymphoma (ATL), and peripheral T-cell lymphoma (PTCL). Mogamulizumab is an anti-CCR4 antibody that has been associated with an increased risk of transplant-related complications in retrospective analyses of ATL, particularly when administered within 50 days before transplantation. This post hoc analysis of 3 clinical trials examined safety and outcome data for 32 patients with CTCL (n = 23), ATL (n = 7), or PTCL (n = 2) who underwent allo-HSCT after mogamulizumab treatment.

Targeting MCL1-driven anti-apoptotic pathways to overcome hypomethylating agent resistance in -mutated chronic myelomonocytic leukemia.

pathway mutations, which are present in 30% of patients with chronic myelomonocytic leukemia (CMML) at diagnosis, confer a high risk of resistance to and progression after hypomethylating agent (HMA) therapy, the current standard of care for the disease. Using single-cell, multi-omics technologies, we sought to dissect the biological mechanisms underlying the initiation and progression of pathway-mutated CMML. We found that pathway mutations induced the transcriptional reprogramming of hematopoietic stem and progenitor cells (HSPCs), which underwent proliferation and monocytic differentiation in response to cell-intrinsic and -extrinsic inflammatory signaling that also impaired immune cells' functions.

Ectonucleoside triphosphate diphosphohydrolase-1 (CD39) impacts TGF-β1 responses: insights into cardiac fibrosis and function following myocardial infarction.

Extracellular purine nucleotides and nucleosides released from activated or injured cells influence multiple aspects of cardiac physiology and pathophysiology. Ectonucleoside triphosphate diphosphohydrolase-1 (ENTPD1; CD39) hydrolyzes released nucleotides and thereby regulates the magnitude and duration of purinergic signaling. However, the impact of CD39 activity on post-myocardial infarction (MI) remodeling is incompletely understood.

Re-imaging healthcare delivery in the era of COVID-19.

The COVID-19 pandemic has exposed the deficiencies of the current healthcare system in terms of a disconnect between primary and tertiary care and increasing subspecialisation, the focus on acute episodic care rather than on prevention in a time where chronic disease prevails and an inefficient use of healthcare resources. Herein, we present the case for an alternative model of healthcare delivery - shared medical appointments - which are efficient, effective and empowering and can be transitioned to the virtual environment successfully. We highlight the barriers to implementation and how these can be overcome.

Too much sugar does not just make us fat; it can also make us sick.

The post-COVID-19 care era is likely to see a burgeoning of metabolic dysfunction and chronic kidney disease. Attention to self-care, including nutrition, will underpin the management of those affected. The damaging effects of sugar-sweetened beverages are well documented and profound and counter many accepted medical treatments.

Burnstock oration - purinergic signalling in kidney transplantation.

Kidney transplantation is the preferred treatment for individuals with kidney failure offering improved quality and quantity of life. Despite significant advancements in short term graft survival, longer term survival rates have not improved greatly mediated in large by chronic antibody mediated rejection. Strategies to reduce the donor kidney antigenic load may translate to improved transplant survival.

Blood Plasma Metabolites in Diabetes-Associated Chronic Kidney Disease: A Focus on Lipid Profiles and Cardiovascular Risk.

Background: We investigated a cross-sectional metabolomic analysis of plasma and urine of patients with early and late stage diabetes associated chronic kidney disease (CKD), inclusive of stages 1-5 CKD, to identify potential metabolomic profiles between the two groups.

Methods: This cross-sectional study recruited 119 adults. Metabolomic biomarkers were quantified in 119 non-fasted plasma and 57 urine samples using a high-throughput proton Nuclear Magnetic Resonance platform.

Impact of COVID-19 on the worsening crisis of chronic kidney disease: the imperative to fund early detection is now.

The number of Australians affected by kidney disease will increase as the impacts of COVID-19 infection on kidney health are realised. Chronic kidney disease (CKD) imposes significant health and economic burdens from dialysis costs, loss of employment, premature death and increased admissions to hospital. Screening for kidney disease must be integrated into post-COVID-19 care; however, currently there is no reimbursement for kidney health checks in primary care.

Clinicians' perspectives on equity of access to dialysis and kidney transplantation for rural people in Australia: a semistructured interview study.

Objectives: People with chronic kidney disease requiring dialysis or kidney transplantation in rural areas have worse outcomes, including an increased risk of hospitalisation and mortality and encounter many barriers to accessing kidney replacement therapy. We aim to describe clinicians' perspectives of equity of access to dialysis and kidney transplantation in rural areas.

Design: Qualitative study with semistructured interviews.

Hematopoiesis under telomere attrition at the single-cell resolution.

The molecular mechanisms that drive hematopoietic stem cell functional decline under conditions of telomere shortening are not completely understood. In light of recent advances in single-cell technologies, we sought to redefine the transcriptional and epigenetic landscape of mouse and human hematopoietic stem cells under telomere attrition, as induced by pathogenic germline variants in telomerase complex genes. Here, we show that telomere attrition maintains hematopoietic stem cells under persistent metabolic activation and differentiation towards the megakaryocytic lineage through the cell-intrinsic upregulation of the innate immune signaling response, which directly compromises hematopoietic stem cells' self-renewal capabilities and eventually leads to their exhaustion.

Lack of impact of type and extent of prior therapy on outcomes of mogamulizumab therapy in patients with cutaneous T cell lymphoma in the MAVORIC trial.

Patients with mycosis fungoides (MF) and Sézary syndrome (SS) often require multiple lines of systemic therapy. In the phase 3 MAVORIC study (NCT01728805), mogamulizumab demonstrated superiority to vorinostat in median progression-free survival (PFS) and confirmed overall response rate (ORR) in patients with MF/SS. This analysis examined the effects of number and type of prior systemic therapies on mogamulizumab response.

Coprocytobiology: A Technical Review of Cytological Colorectal Cancer Screening in Fecal Samples.

This review discusses the field of coprocytobiology, defined as a combined method of cell preservation, isolation, and cytology, which has applications to the investigation of noninvasive fecal screening for colorectal cancer. In the decade since the field was last reviewed, cell isolation has progressed rapidly via the development of technologies such as microfluidic and magnetic cell sorting. The landscape of cytology has also advanced in this time with the emergence of novel cytological methods and cell preservation strategies.

Gut Microbiome Composition Remains Stable in Individuals with Diabetes-Related Early to Late Stage Chronic Kidney Disease.

(1) Background: Individuals with diabetes and chronic kidney disease display gut dysbiosis when compared to healthy controls. However, it is unknown whether there is a change in dysbiosis across the stages of diabetic chronic kidney disease. We investigated a cross-sectional study of patients with early and late diabetes associated chronic kidney disease to identify possible microbial differences between these two groups and across each of the stages of diabetic chronic kidney disease.

DNA methylation profiling identifies epigenetic differences between early versus late stages of diabetic chronic kidney disease.

Background: We investigated a cross-sectional epigenome-wide association study of patients with early and late diabetes-associated chronic kidney disease (CKD) to identify possible epigenetic differences between the two groups as well as changes in methylation across all stages of diabetic CKD. We also evaluated the potential of using a panel of identified 5'-C-phosphate-G-3' (CpG) sites from this cohort to predict the progression of diabetic CKD.

Methods: This cross-sectional study recruited 119 adults.