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Doege–Potter Syndrome (DPS) is a rare paraneoplastic cause of hypoglycaemia, arising from solitary fibrous tumours (SFTs) that ectopically secrete insulin‐like growth factor II (IGF‐II). We report a case of DPS in a 76‐year‐old man presenting with recurrent severe hypoglycaemia. Biochemistry investigations revealed hypoglycaemia with suppressed insulin, C‐peptide and beta‐hydroxybutyrate levels. Magnetic resonance imaging (MRI) confirmed a giant (205 × 190 × 169 mm) right pleurally‐based SFT. Hypoglycaemia was managed with intravenous dextrose infusion and glucagon until surgical resection via thoracotomy. A massive transfusion protocol was activated for intra‐operative bleeding. Histopathology confirmed a spindle cell SFT without malignant features. Post‐operative blood glucose levels normalised, and the patient was discharged without complication. This case highlights the diagnostic challenges of DPS, the potential to maintain pre‐operative normoglycaemia without glucocorticoid therapy and the importance of recognising tumour vascularity to guide pre‐operative planning and reduce bleeding risk. We describe a case of Doege–Potter syndrome from a giant pleural solitary fibrous tumour in a 76‐year‐old male. This case highlights the potential for maintaining pre‐operative normoglycaemia without glucocorticoids and emphasises recognising tumour vascularity on imaging to anticipate intra‐operative bleeding risk.

Background The management of malignant pleural effusion (MPE) is inconsistent across health services. Many centres do not routinely offer all treatment options for MPE, with indwelling pleural catheter (IPC) being a primary example. This may be due to lack of specialist expertise or nursing capability to support the community‐based treatment. New approaches are required to improve access to MPE treatments. This proof‐of‐concept study examines the feasibility of a virtual model of care for MPE, known as the specialist ambulatory pleural service (SAPS) model of care. This model will be compared with current approaches at other health services in the state, in terms of healthcare utilisation and costs. It will also assess health‐related quality of life in individuals with MPE and report patient, carer and nurse experiences with the SAPS model of care. Methods A prospective, multi‐centre, mixed‐methods study will be performed. Participants with symptomatic MPE requiring intervention will be consecutively enrolled. The primary outcome is pleural effusion‐related hospitalisation from enrolment to death or end of study participation. Secondary outcomes include: Overall hospitalisation, unplanned pleural effusion‐related outpatient and emergency department (ED) visits, pleural‐related healthcare costs, adverse events, overall survival, percentage of screened patients recruited, percentage dropped out/lost to follow up, percentage of scheduled home visits carried out, percentage of teleultrasound assessments completed, technical issues, percentage of symptom logbooks completed, quality of life, longitudinal symptom monitoring, participant and nursing attitudes to the SAPS model of care, patient activation measure and a stakeholder interview of the SAPS model of care implementation. Discussion Digital health may improve access to MPE treatments by reducing barriers to specialist care and facilitating training and support for community staff. This trial assesses the SAPS model of care, providing data on barriers and facilitators to its implementation, its efficacy, costs and qualitative outcomes. Trial Registration: Australia New Zealand Clinical Trial Registry: ACTRN12623000063617; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=384448&isReview=true. Digital health may improve access to MPE treatments by reducing barriers to specialist care and facilitating training and support for community staff. This trial assesses the SAPS model of care, providing data on barriers and facilitators to its implementation, its efficacy, costs and qualitative outcomes.

Repaired compressors are compared with remanufactured and new compressors in terms of economic and environmental benefits. A detailed life cycle assessment has been carried out for compressors under three manufacturing strategies: repaired, remanufactured and new equipment. The life cycle assessment of the global warming potential of repaired compressors varies from 4.38 to 119 kg carbon dioxide equivalent (CO2-e), depending on the type of components replaced. While greenhouse gas emissions from the remanufactured compressors (110 to 168 kg CO2-e) are relatively higher than those from the repaired ones (4.4 to 119 kg CO2-e), a new compressor has been found to produce a larger amount of greenhouse gas emissions (1,590 kg CO2-e) compared to both repaired and remanufactured compressors. Repairing failed compressors has been found to offer end users both dollar and carbon savings in contrast to remanufactured and new compressors. The research also found that extended lifetime is more important than the manufacturing processes in terms of greenhouse gas emissions. Since a remanufactured compressor offers a longer life than a repaired compressor, the replacement of the latter with the former can avoid 33% to 66% of the greenhouse gas emissions associated with a new compressor production with a lifetime of 15 to 25 years.

Henipaviruses, such as Hendra and Nipah viruses, are major zoonotic pathogens that cause encephalitis and respiratory infections in humans and animals. The recent emergence of Langya virus in China highlights the need to understand henipavirus host diversity and geographic spread to prevent future outbreaks. Our analysis of the National Center for Biotechnology Information Virus and VIRION databases revealed ≈1,117 henipavirus sequences and 142 complete genomes. Bats (64.7%) and shrews (11.7%) dominated the host species record, and the genera Pteropus and Crocidura contained key henipavirus hosts in Asia, Australia, and Africa. Henipaviruses found in the Eidolon bat genus exhibited the highest within-host genetic distance. Phylogenetic analysis revealed batborne and rodent- or shrew-derived henipaviruses diverged ≈11,000 years ago and the first known lineage originating in Eidolon genus bats ≈9,900 years ago. Pathogenic henipaviruses diverged from their ancestors 2,800-1,200 years ago. Including atypical hosts and regions in future investigations is necessary to control future outbreaks.

The spread of SARS-CoV-2 has led to a devastating pandemic, with infections resulting in a range of symptoms collectively known as COVID-19. The full repertoire of human tissues and organs susceptible to infection is an area of active investigation, and some studies have implicated the reproductive system. The effects of COVID-19 on human reproduction remain poorly understood, and particularly the impact on early embryogenesis and establishment of a pregnancy are not known. In this work, we explore the susceptibility of early human embryos to SARS-CoV-2 infection. By using RNA-seq and immunofluorescence, we note that ACE2 and TMPRSS2, two canonical cell entry factors for SARS-CoV-2, are co-expressed in cells of the trophectoderm in blastocyst-stage preimplantation embryos. For the purpose of viral entry studies, we used fluorescent reporter virions pseudotyped with Spike (S) glycoprotein from SARS-CoV-2, and we observe robust infection of trophectoderm cells. This permissiveness could be attenuated with blocking antibodies targeting S or ACE2. When exposing human blastocysts to the live, fully infectious SARS-CoV-2, we detected cases of infection that compromised embryo health. Therefore, we identify a new human target tissue for SARS-CoV-2 with potential medical implications for reproductive health during the COVID-19 pandemic and its aftermath.

Background Pharmacies often restrict access to over the counter (OTC) syringes. The objective of this study was to quantify the frequency that patients experience barriers when seeking to purchase a 10-pack of OTC syringes from community pharmacies in Oregon. Methods To ascertain the availability of a 10-pack of OTC syringes, we conducted a telephone audit (“secret shopper”) study of Oregon community pharmacies. Descriptive statistics and binomial logistic regressions were then performed to identify factors associated with willingness to sell a syringe 10-pack OTC. Factors included in the analysis were related to pharmacy type (chain vs. independent) and county characteristics (rurality, syringe service program presence, overdose rate). Results We contacted 425 pharmacies (361 chain, 64 independent) between December 2023 and March 2024; of those, 62.8% were in urban counties. Staff at 184 (43.3%) pharmacies reported that they would not sell a syringe 10-pack OTC. Urban pharmacies were more likely to restrict OTC syringe sales compared to rural pharmacies (adjusted odds ratio [2.11]; 95% CI [1.22–3.65]). No significant differences existed between chain and independent pharmacies. Conclusions Community pharmacies are well positioned to ensure access to sterile syringes, but our findings show that they are unreliable access points as nearly half of Oregon community pharmacies restrict patient access to OTC syringes. Unwillingness to sell OTC syringes was most pronounced in urban counties. Pharmacy-directed efforts are needed to ensure access to sterile syringes and address unmet health needs for people who inject drugs.

Mitochondria influence cellular function through both cell-autonomous and non-cell autonomous mechanisms, such as production of paracrine and endocrine factors. Here, we demonstrate that mitochondrial regulation of the secretome is more extensive than previously appreciated, as both genetic and pharmacological disruption of the electron transport chain caused upregulation of the Alzheimer’s disease risk factor apolipoprotein E (APOE) and other secretome components. Indirect disruption of the electron transport chain by gene editing of SLC25A mitochondrial membrane transporters as well as direct genetic and pharmacological disruption of either complexes I, III, or the copper-containing complex IV of the electron transport chain elicited upregulation of APOE transcript, protein, and secretion, up to 49-fold. These APOE phenotypes were robustly expressed in diverse cell types and iPSC-derived human astrocytes as part of an inflammatory gene expression program. Moreover, age- and genotype-dependent decline in brain levels of respiratory complex I preceded an increase in APOE in the 5xFAD mouse model. We propose that mitochondria act as novel upstream regulators of APOE-dependent cellular processes in health and disease.

Neuroinflammation plays a critical role in Alzheimer's disease pathogenesis. Neurons are anatomically divided in subcellular compartments (axons, soma, and synapses), which may be distinctly impacted by neuroinflammation. This study aims to examine cellular compartment-specific proteomic signatures in excitatory neurons following a systemic neuroinflammatory stress. We used our innovative CIBOP (cell type-specific in vivo biotinylation of proteins) approach to selectively label Camk2a excitatory neuron proteomes in vivo. Neuron-CIBOP transgenic mice and their littermate controls were treated with lipopolysaccharide (LPS, [500 µg/kg, i.p.]) during 4 consecutive days, which induces robust microglial activation and sickness behavior. After euthanasia, brains were quickly removed, and crude synaptosomal fractions (P2 fractions) were prepared by differential centrifugation. Neuron-specific biotinylated proteins were then enriched and analyzed by label-free quantitative mass spectrometry (MS) to identify differentially-enriched proteins (DEPs) and biological pathways (by gene set variation analysis/GSVA). Neuron-derived biotinylated key cellular signaling pathways (MAPK and Akt/mTOR) were directly measured by Luminex in homogenates and P2 fractions (Fig. 1A). Electron micrographs validated the subcellular composition of the P2 fractions showing synaptosomes containing synaptic vesicles and mitochondria (Fig. 1B). MS studies confirmed that neuronal homogenates were enriched in microtubule and cytoskeleton-related proteins, while P2 fractions were enriched in mitochondria and synapse-related proteins (Fig. 1C). Interestingly, LPS induced unique compartment-specific proteomic effects, P2 fraction has 52 unique DEPs, while homogenate has 57 DEPs, and only 2 DEPs overlapped (Fig. 1D). Neuronal homogenate proteomes showed upregulation of detoxification and oxidoreductase activity, while a reduced neuron-synapse, somatodendritic compartment, and cytoskeleton organization. In P2 fraction proteomes, LPS upregulated mitochondrial envelope formation and metabolic activity, including purine containing compound metabolic process, but downregulated nucleoside triphosphate regulator activity. Increased aerobic respiration and mitochondria response overlapped among compartments (Fig. 1E). We also observed LPS-induced decrease in MAPK signaling specifically in the P2 fraction, not evident at the level of whole neurons, nor at the bulk brain tissue level (Fig. 1F). Our neuron and synaptosome-enriched proteomics approach revealed unique molecular and signaling effects of neuroinflammation that may preferentially impact the synapses of excitatory neurons.

Chronic liver disease and hepatocellular carcinoma (HCC) are life-threatening diseases with limited treatment options. The lack of clinically relevant/tractable experimental models hampers therapeutic discovery. Here, we develop a simple and robust human liver cell-based system modeling a clinical prognostic liver signature (PLS) predicting long-term liver disease progression toward HCC. Using the PLS as a readout, followed by validation in nonalcoholic steatohepatitis/fibrosis/HCC animal models and patient-derived liver spheroids, we identify nizatidine, a histamine receptor H2 (HRH2) blocker, for treatment of advanced liver disease and HCC chemoprevention. Moreover, perturbation studies combined with single cell RNA-Seq analyses of patient liver tissues uncover hepatocytes and HRH2 + , CLEC5A high , MARCO low liver macrophages as potential nizatidine targets. The PLS model combined with single cell RNA-Seq of patient tissues enables discovery of urgently needed targets and therapeutics for treatment of advanced liver disease and cancer prevention. Drug and target discovery for advanced liver disease are hampered by a lack of suitable models for clinical translation. Here the authors present a human liver cell-based system modeling a clinical prognostic signature allowing to propose nizatidine for treatment of advanced liver fibrosis and hepatocellular carcinoma prevention.

We integrated lipidomics and genomics to unravel the genetic architecture of lipid metabolism and identify genetic variants associated with lipid species putatively in the mechanistic pathway for coronary artery disease (CAD). We quantified 596 lipid species in serum from 4,492 individuals from the Busselton Health Study. The discovery GWAS identified 3,361 independent lipid-loci associations, involving 667 genomic regions (479 previously unreported), with validation in two independent cohorts. A meta-analysis revealed an additional 70 independent genomic regions associated with lipid species. We identified 134 lipid endophenotypes for CAD associated with 186 genomic loci. Associations between independent lipid-loci with coronary atherosclerosis were assessed in ∼456,000 individuals from the UK Biobank. Of the 53 lipid-loci that showed evidence of association ( P  < 1 × 10 −3 ), 43 loci were associated with at least one lipid endophenotype. These findings illustrate the value of integrative biology to investigate the aetiology of atherosclerosis and CAD, with implications for other complex diseases. Dysregulation of lipid metabolism is associated with coronary artery disease (CAD). Here, the authors perform GWAS of the serum lipidome to identify variants associated with lipid species that are putatively in the mechanistic pathway to CAD.