Assessing the content validity of patient reported outcome measure item pool for rheumatoid arthritis disease activity using cognitive interviews.

Objectives: Using Rasch measurement theory, an item pool of 12 questions has been identified, covering tenderness and swelling, disease activity, pain, physical functioning and stiffness for assessing the construct of RA disease activity. This study aimed to assess the content validity of this item pool using cognitive interviews.

Methods: Participants were randomly sampled across varying age, sex and education level categories from respondents to a survey containing RA disease activity Patient Reported Outcome Measures.

Non-invasive ventilation in COVID-19-related acute hypoxemic respiratory failure: a narrative review.

The high mortality rate and extended ventilator use associated with invasive mechanical ventilation in patients with severe COVID-19 have sparked a debate about the use of non-invasive respiratory support, such as high-flow nasal cannula, continuous positive airway pressure, and non-invasive ventilation (NIV), as treatment options. According to the European Respiratory Society and the American Thoracic Society clinical practice guidelines, NIV is recommended to prevent intubation in hypoxemic acute respiratory failure in patients with community-acquired pneumonia or early acute respiratory distress syndrome without major organ dysfunction. Central to this debate is the role of NIV in managing acute hypoxemic respiratory failure.

Participants' perspectives of the advanced ovarian cancer biomarker study VALTIVE1: a qualitative study.

Objectives: VALTIVE1 is a multi-centre, single-arm, non-interventional biomarker study for patients with advanced ovarian cancer. Plasma samples (Tie2 concentration) are collected to detect vascular control in tumours during standard treatment with chemotherapy and bevacizumab. This qualitative study embedded in VALTIVE1 aimed to assess the acceptability and feasibility of a potential VALTIVE2 trial.

Mechanisms of Lung Cancer Development in Cystic Fibrosis Patients: The Role of Inflammation, Oxidative Stress, and Lung Microbiome Dysbiosis.

Cystic fibrosis (CF) is a genetic disorder caused by mutations in the CFTR gene, leading to defective ion transport and impaired function of various organs. Chronic inflammation, oxidative stress, and microbial dysbiosis are key pathological features of CF patients, contributing to disease progression, lung damage, and an increased susceptibility to infections. Emerging evidence suggests that in CF patients these factors can promote cancer development, especially lung cancer.

Consensus Guideline for the Management of Colorectal Cancer with Peritoneal Metastases.

Background: The peritoneum is a common site of metastases from colorectal cancer (CRC), yet controversy exists regarding optimal treatment strategies. These guidelines describe the results of a national consensus addressing the management of CRC with peritoneal metastases (CRC-PM).

Methods: An update of the 2018 Chicago Consensus Guidelines was conducted using a modified Delphi technique.

Consensus guideline for the management of colorectal cancer with peritoneal metastases.

The peritoneum is a common site of metastases from colorectal cancer (CRC), yet controversy exists regarding optimal treatment strategies. These guidelines describe the results of a national consensus addressing the management of CRC with peritoneal metastases (CRC-PM). An update of the 2018 Chicago consensus guidelines was conducted with a modified Delphi technique.

A Multicenter Observational Study Comparing Survival of Pugs and Dogs of Other Breeds With Protein-Losing Enteropathy.

Background: Protein-losing enteropathy (PLE) in dogs often carries a guarded prognosis, and it is unclear if survival differs among breeds.

Hypothesis/objectives: Survival of pugs with PLE is shorter than that of other breeds of dogs with PLE.

Animals: Forty-seven pugs and 148 dogs of other breeds were diagnosed with PLE at seven United Kingdom (UK) referral hospitals.

Patient Reported Outcome Measures for Rheumatoid Arthritis Disease Activity: Rasch measurement theory to identify items and domains.

Objectives: Disease activity (DA) monitoring is a standard of care in RA. There is demand for achieving this through patient-reported outcome measures (PROMs). The aim of this study was to determine which items could be used to measure the construct of RA DA, by analysing legacy PROMs, using Rasch measurement theory (RMT) analyses.

Case report: Selpercatinib in the treatment of fusion-positive advanced lung adenocarcinoma: a challenging clinical case.

Background: Rearranged during transfection () fusions represent a distinct molecular subset of non-small cell lung cancer (NSCLC) with targeted therapeutic potential. Selpercatinib, a highly selective inhibitor, has demonstrated efficacy in various solid tumors harboring alterations. Here, we present a case highlighting the use and clinical outcomes of selpercatinib in a patient diagnosed with advanced lung adenocarcinoma harboring a fusion.

The impact of specialised gastroenterology services for pelvic radiation disease (PRD): Results from the prospective multi-centre EAGLE study.

To undertake a mixed-methodology implementation study to improve the well-being of men with gastrointestinal late effects following radical radiotherapy for prostate cancer. All men completed a validated screening tool for late bowel effects (ALERT-B) and the Gastrointestinal Symptom Rating Score (GSRS); men with a positive score on ALERT-B were offered management following a peer reviewed algorithm for pelvic radiation disease (PRD). Health-related quality of life (HRQoL) at baseline, 6 and 12 months; and healthcare resource usage (HRU) and patient, support-giver, staff experience and acceptability of staff training (qualitative analysis) were assessed.

The VALTIVE1 study protocol: a study for the validation of Tie2 as the first tumour vascular response biomarker for VEGF inhibitors.

Background: Anti-angiogenic, VEGF inhibitors (VEGFi) increase progression-free survival (PFS) and, in some cases, overall survival in many solid tumours. However, their use has been compromised by a lack of informative biomarkers. We have shown that plasma Tie2 is the first tumour vascular response biomarker for VEGFi in ovarian, colorectal and gall bladder cancer: If plasma Tie2 concentrations do not change after 9 weeks of treatment with a VEGFi, the patient does not benefit, whereas a confirmed reduction of at least 10% plasma Tie2 defines a vascular response with a hazard ratio (HR) for PFS of 0.

eIF2B localization and its regulation during the integrated stress response is cell-type specific.

Eukaryotic initiation factor 2B (eIF2B) controls translation initiation by recycling inactive eIF2-GDP to active eIF2-GTP. Under cellular stress, the integrated stress response (ISR) is activated inhibiting eIF2B activity resulting in the translation attenuation and reprogramming of gene expression to overcome the stress. The ISR can dictate cell fate wherein chronic activation has pathological outcomes.

Astrocytes require perineuronal nets to maintain synaptic homeostasis in mice.

Perineuronal nets (PNNs) are densely packed extracellular matrices that cover the cell body of fast-spiking inhibitory neurons. PNNs stabilize synapses inhibiting synaptic plasticity. Here we show that synaptic terminals of fast-spiking interneurons localize to holes in the PNNs in the adult mouse somatosensory cortex.

TRPV1 and mast cell involvement in repeated variate stress-induced urinary bladder dysfunction in adult female mice.

The etiology of interstitial cystitis/bladder pain syndrome (IC/BPS) is unknown but likely multifactorial. IC/BPS symptoms can be exacerbated by psychological stress, but underlying mechanisms remain to be defined. Transient receptor potential vanilloid 1 (TRPV1) channels, expressed on nerve fibers, have been implicated in bladder dysfunction and colonic hypersensitivity with stress in rodents.

Strand-resolved mutagenicity of DNA damage and repair.

DNA base damage is a major source of oncogenic mutations. Such damage can produce strand-phased mutation patterns and multiallelic variation through the process of lesion segregation. Here we exploited these properties to reveal how strand-asymmetric processes, such as replication and transcription, shape DNA damage and repair.

The Differential Translation Capabilities of the Human DHFR2 Gene Indicates a Developmental and Tissue-Specific Endogenous Protein of Low Abundance.

A functional role has been ascribed to the human dihydrofolate reductase 2 (DHFR2) gene based on the enzymatic activity of recombinant versions of the predicted translated protein. However, the in vivo function is still unclear. The high amino acid sequence identity (92%) between DHFR2 and its parental homolog, DHFR, makes analysis of the endogenous protein challenging.

Utilizing Molecular Epidemiology and Citizen Science for the Surveillance of Lagoviruses in Australia.

Australia has multiple lagoviruses with differing pathogenicity. The circulation of these viruses was traditionally determined through opportunistic sampling events. In the lead up to the nationwide release of RHDVa-K5 (GI.

Topiramate alters the gut microbiome to aid in its anti-seizure effect.

Introduction: There is a growing interest in the role of the gut microbiota in epilepsy, however, it is unclear if anti-seizure medications (ASMs) play a role in the gut-brain axis. To test this, we investigated the impact of the ASM topiramate on the gut microbiome of mice.

Methods: C57BL/6J mice were administered topiramate in their drinking water for 5 weeks.

Stress-induced symptom exacerbation: Stress increases voiding frequency, somatic sensitivity, and urinary bladder NGF and BDNF expression in mice with subthreshold cyclophosphamide (CYP).

Symptom exacerbation due to stress is prevalent in many disease states, including functional disorders of the urinary bladder (e.g., overactive bladder (OAB), interstitial cystitis/bladder pain syndrome (IC/BPS)); however, the mechanisms underlying the effects of stress on micturition reflex function are unclear.

Lung Microbiome as a Treatable Trait in Chronic Respiratory Disorders.

Once thought to be a sterile environment, it is now established that lungs are populated by various microorganisms that participate in maintaining lung function and play an important role in shaping lung immune surveillance. Although our comprehension of the molecular and metabolic interactions between microbes and lung cells is still in its infancy, any event causing a persistent qualitative or quantitative variation in the composition of lung microbiome, termed "dysbiosis", has been virtually associated with many respiratory diseases. A deep understanding of the composition and function of the "healthy" lung microbiota and how dysbiosis can cause or participate in disease progression will be pivotal in finding specific therapies aimed at preventing diseases and restoring lung function.

Repeated variate stress increased voiding frequency and altered TrpV1 and TrpV4 transcript expression in lower urinary tract (LUT) pathways in female mice.

Psychological stress is associated with urinary bladder dysfunction (e.g., increased voiding frequency, urgency and pelvic pain); however, the mechanisms underlying the effects of stress on urinary bladder function are unknown.

MALDI and Trace Metal Analysis in Age-Related Macular Degeneration.

Age-related macular degeneration (AMD) remains one of the most prevalent causes of blindness throughout the world. Key to prevention of AMD is furthering the understanding of its pathology. In recent years, both the proteins within the innate immune system and essential and non-essential metals have been implicated in the pathology of AMD.

Sustained Impact of RHDV2 on Wild Rabbit Populations across Australia Eight Years after Its Initial Detection.

Following the arrival of rabbit haemorrhagic disease virus 2 (RHDV2) in Australia, average rabbit population abundances were reduced by 60% between 2014 and 2018 based on monitoring data acquired from 18 sites across Australia. During this period, as the seropositivity to RHDV2 increased, concurrent decreases were observed in the seroprevalence of both the previously circulating RHDV1 and RCVA, a benign endemic rabbit calicivirus. However, the detection of substantial RHDV1 seropositivity in juvenile rabbits suggested that infections were continuing to occur, ruling out the rapid extinction of this variant.

Dysregulation of Stress-Induced Translational Control by in Host Cells.

contributes to the chronic oral disease periodontitis, triggering the activation of host inflammatory responses, inducing cellular stresses such as oxidation. During stress, host cells can activate the Integrated Stress Response (ISR), a pathway which determines cellular fate, by either downregulating protein synthesis and initiating a stress-response gene expression program, or by initiating programmed cell death. Recent studies have implicated the ISR within both host antimicrobial defenses and the pathomechanism of certain microbes.

Perineuronal nets support astrocytic ion and glutamate homeostasis at tripartite synapses.

Perineuronal nets (PNNs) are dense, negatively charged extracellular matrices that cover the cell body of fast-spiking inhibitory neurons. Synapses can be embedded and stabilized by PNNs believed to prevent synaptic plasticity. We find that in cortical fast-spiking interneurons synaptic terminals localize to perforations in the PNNs, 95% of which contain either excitatory or inhibitory synapses or both.