Structure, function, surf, repeat: A week at Lorne Proteins 2024.

Since 1976, the Lorne Proteins Conference has been a key gathering for protein scientists, combining cutting-edge research with community engagement in a picturesque corner of the world. Renowned for its diverse international speakers and collaborative spirit, the conference looks forward to its 50 anniversary in 2025.

Improving cancer outcomes through enhanced leadership and strategy training for cancer healthcare professionals - A course developed by the European School of Oncology (ESO), the European Cancer Organization (ECO) and Sharing Progress in Cancer Care (SPCC).

Leadership as a key building block of a health system plays a crucial role in achieving high performance and helps deliver change and shape the policy agenda and its implementation. Echoing the emerging need for effective leaders in Oncology, the "Improving Cancer Outcomes and Leadership Course" was developed jointly by the European School of Oncology (ESO), the European Cancer Organization (ECO) and Sharing Progress in Cancer Care (SPCC). The course was offered as a hybrid event online and in Warsaw in June 2022.

Autosomal recessive -related disorder: comprehensive analysis of phenotypic variability and genetic mutations.

A newly identified subtype of hereditary axonal motor neuropathy, characterized by early proximal limb involvement, has been discovered in a cohort of 34 individuals with biallelic variants in von Willebrand factor A domain-containing 1 (). This study further delineates the disease characteristics in a cohort of 20 individuals diagnosed through genome or exome sequencing, incorporating neurophysiological, laboratory and imaging data, along with data from previously reported cases across three different studies. Newly reported clinical features include hypermobility/hyperlaxity, axial weakness, dysmorphic signs, asymmetric presentation, dystonic features and, notably, upper motor neuron signs.

Combined inhibition of histone methyltransferases EZH2 and DOT1L is an effective therapy for neuroblastoma.

Background: The child cancer, neuroblastoma (NB), is characterised by a low incidence of mutations and strong oncogenic embryonal driver signals. Many new targeted epigenetic modifier drugs have failed in human trials as monotherapy.

Methods: We performed a high-throughput, combination chromatin-modifier drug screen against NB cells.

Heightened mitochondrial respiration in CF cells is normalised by triple CFTR modulator therapy through mechanisms involving calcium.

Background: Cystic fibrosis (CF) is associated with increased resting energy expenditure. However, the introduction of elexacaftor/tezacaftor/ivacaftor (ETI) has resulted in a paradigm shift in nutritional status for many people with CF, with increase body mass index and reduction in the need for nutritional support. While these changes are likely to reflect improved clinical status and an associated downregulation of energy expenditure, they may also reflect drug-induced alterations in metabolic perturbations within CF cells.

Left ventricular size and heart failure: A cardiac MRI assessment of 38,129 individuals from the UK Biobank.

Background: Previous studies suggest that prevalent heart failure (HF) differs based on left ventricular ejection fraction (LVEF) and left ventricular (LV) chamber size. Furthermore, the prevalence of HF with preserved ejection fraction (HFpEF) is often considered approaching, or exceeding that of HF with reduced ejection fraction in the community.

Aim: The aim of this study was to evaluate prevalent and incident HF based on LVEF and CMR-determined LV size within a large community-dwelling cohort.

Left Ventricular Volume as a Predictor of Exercise Capacity and Functional Independence in Individuals with Normal Ejection Fraction.

Aims: Low cardiorespiratory fitness (CRF) is associated with functional disability, heart failure and mortality. Left ventricular (LV) end-diastolic volume (LVEDV) has been linked with CRF, but its utility as a diagnostic marker of low CRF has not been tested.

Methods: This multi-center international cohort examined the relationship between LV size on echocardiography and CRF (peak oxygen uptake [peak VO2] from cardiopulmonary exercise testing) in individuals with LV ejection fraction ≥50%.

Cell Populations in Human Breast Cancers are Molecularly and Biologically Distinct with Age.

Aging is associated with increased breast cancer risk and outcomes are worse for the oldest and youngest patients, regardless of subtype. It is not known how cells in the breast tumor microenvironment are impacted by age and how they might contribute to age-related disease pathology. Here, we discover age-associated differences in cell states and interactions in human estrogen receptor-positive (ER+) and triple-negative breast cancers (TNBC) using new computational analyses of existing single-cell gene expression data.

Paraneoplastic progressive encephalomyelitis with rigidity and myoclonus associated with monoclonal B-cell lymphocytosis in the setting of longstanding methotrexate use: case report.

Progressive encephalomyelitis with rigidity and myoclonus (PERM) is a rare but debilitating disease within the stiff person syndrome (SPS) spectrum characterised by muscle rigidity, spasms, myoclonus, dysautonomia, and brainstem dysfunction. The exact pathogenetic mechanism is unclear, although there is an association with the presence of glycine receptor antibodies in serum and cerebrospinal fluid, and some cases are paraneoplastic. Here, we report a case of paraneoplastic, glycine receptor antibody-positive PERM associated with an otherwise subclinical monoclonal B-cell lymphocytosis (MBL) of the non-CLL phenotype, which may be, in turn, likely secondary to long-term methotrexate use [i.

Promising biomarker panel to monitor therapeutic efficacy of neoadjuvant chemotherapy in pancreatic cancer patients.

Background: Neoadjuvant chemotherapy (NAC) can provide improved survival outcomes in pancreatic ductal adenocarcinoma (PDAC) patients who respond to treatment, but currently available biomarkers cannot reliably predict NAC response. This study aimed to determine the potential of a previously identified diagnostic and prognostic biomarker panel (i.e.

Auto-Abs neutralizing type I IFNs in patients with severe Powassan, Usutu, or Ross River virus disease.

Arboviral diseases are a growing global health concern. Pre-existing autoantibodies (auto-Abs) neutralizing type I interferons (IFNs) can underlie encephalitis due to West Nile virus (WNV) (∼40% of patients) and tick-borne encephalitis (TBE, due to TBE virus [TBEV]) (∼10%). We report here that these auto-Abs can also underlie severe forms of rarer arboviral infections.

Comparison of Posttherapy 4- and 24-Hour [Lu]Lu-PSMA SPECT/CT and Pretherapy PSMA PET/CT in Assessment of Disease in Men with Metastatic Castration-Resistant Prostate Cancer.

[Lu]Lu-prostate-specific membrane antigen (PSMA) is an effective treatment for metastatic castration-resistant prostate cancer (mCRPC). [Lu]Lu-PSMA SPECT/CT 24 h after injection has shown potential as a response biomarker for [Lu]Lu-PSMA therapy but is not convenient for patients. This study investigated 4-h [Lu]Lu-PSMA SPECT/CT as an alternative to 24-h [Lu]Lu-PSMA SPECT/CT for evaluation of treatment response.

Assessing the impact of a dedicated referral and management algorithm in maternal hypothyroidism.

Background: The significant risks of hypothyroidism during pregnancy can be mitigated through timely diagnosis and initiation of thyroxine to achieve a maternal euthyroid state. This study aimed to evaluate the efficiency of hospital endocrine services by assessing the rate of thyroxine commencement before the initial clinic appointment, the median gestational age at the first consultation, the rate of guideline-appropriate investigations, perinatal outcomes, and the proportion of referred patients who achieved their target thyroid-stimulating hormone (TSH) levels before and after implementing a dedicated referral and management pathway.

Methods: A retrospective clinical audit was conducted using electronic medical records for the first fifty consecutive patients with hypothyroidism referred to the hospital clinic during two-time intervals: from April 1 to September 1, 2020 (pre-intervention) and from April 1 to September 1, 2021 (postintervention).

A near-complete genome of the uncultured phage COMBAT-CF_PAR1 isolated from the lungs of an infant with cystic fibrosis.

In cystic fibrosis, bacteria-bacteriophage interaction in the lower airways is poorly understood. We present the near-complete genome of the uncultured Siphovirus-like bacteriophage, phage COMBAT-CF_PAR1, isolated from the lower airways. The genome spans 41,510 bp with 33.

Medicine Access Programmes: what do patients think - a patient-reported outcome study on ribociclib in metastatic breast cancer in Australia.

This study evaluated patient-reported outcomes (PROs) of Medicine Access Programmes (MAPs) for Australian metastatic breast cancer patients on ribociclib. Limited patient awareness of MAP enrolment was identified, emphasising the need for improved education and consent processes. Most patients expressed gratitude for accessing non-funded medications and perceived enhanced medication adherence as a key benefit.

Impact of whole-body and skeletal muscle composition on peak oxygen uptake in heart failure: a systematic review and meta-analysis.

Aims: Heart failure (HF) has a major impact on exercise tolerance that may (in part) be due to abnormalities in body and skeletal muscle composition. This systematic review and meta-analysis aims to assess how differences in whole-body and skeletal muscle composition between patients with HF and non-HF controls (CON) contribute to reduced peak oxygen uptake (VOpeak).

Methods And Results: The PubMed database was searched from 1975 to May 2024 for eligible studies.

The structure of the IL-11 signalling complex provides insight into receptor variants associated with craniosynostosis.

Interleukin 11 (IL-11), a member of the IL-6 family of cytokines, has roles in haematopoiesis, inflammation, bone metabolism, and craniofacial development. IL-11 also has pathological roles in chronic inflammatory diseases, fibrosis, and cancer. In this structural snapshot, we explore our recently published cryo-EM structure of the human IL-11 signalling complex to understand the molecular mechanisms of complex formation and disease-associated mutations.