The genomic and clinical consequences of replacing procarbazine with dacarbazine in escalated BEACOPP for Hodgkin lymphoma: a retrospective, observational study.

Background: Procarbazine-containing chemotherapy regimens are associated with cytopenias and infertility, suggesting stem-cell toxicity. When treating Hodgkin lymphoma, procarbazine in escalated-dose bleomycin-etoposide-doxorubicin-cyclophosphamide-vincristine-procarbazine-prednisolone (eBEACOPP) is increasingly replaced with dacarbazine (eBEACOPDac) to reduce toxicity. We aimed to investigate the impact of this drug substitution on the mutation burden in stem cells, patient survival, and toxicity.

Transmission of Swine Influenza A Viruses along Pig Value Chains, Cambodia, 2020-2022.

We analyzed >4,000 pig samples from slaughterhouses in Cambodia and found higher influenza A seroprevalence (40.0%) and prevalence (1.5%) among pigs from commercial farms than smallholder farms (seroprevalence 8.

High throughput electronic detection of biomarkers using enzymatically amplified metallization on nanostructured surfaces.

Enzyme-linked immunosorbent assays are commonly used for clinical biomarker detection. However, they remain resource-intensive and difficult to scale globally. Here we present a miniaturized direct electronic biosensing modality which generates a simple and sensitive, quantitative, resistive readout of analyte binding in immunoassays.

Assays for Monitoring Apixaban and Rivaroxaban in Emergency Settings, State-of-the-Art Routine Analysis, and Volumetric Absorptive Microsamples Deliver Discordant Results.

Our aim was to compare the performance of complementary clinical laboratory approaches to monitoring exposure to apixaban and rivaroxaban, the most prescribed direct-acting oral anticoagulants (DOAC's): an automated commercial anti-Xa chromogenic assay suitable for emergency and pre-surgery testing and a laboratory-developed liquid chromatography-tandem mass spectrometry (LC-MS/MS) method employed for non-emergency analysis in plasma and in dried blood volumetric absorptive microsamples (VAMS) collectible by the patients in their homes. The full validation of the LC-MS/MS method was performed. Cross-validation of the methodologies was accomplished by processing 60 specimens collected for whole blood count and DOAC monitoring in a central clinical laboratory.

Stability of inflammation markers in human blood collected using volumetric absorptive microsampling (VAMS) under typical laboratory storage temperatures.

Dried blood spots (DBS) collected on filter paper such as Guthrie cards are stored for years at room temperature. The assumption is that once dried, the samples remain stable and quantifiable indefinitely since the metabolites these were initially designed to measure, are known for their extended stability. The concentration of other blood proteins such as cytokines, however, are known to vary with storage even in liquid samples stored at -80 °C for extended periods of time.

The genomic landscape of swine influenza A viruses in Southeast Asia.

Swine are a primary source for the emergence of pandemic influenza A viruses. The intensification of swine production, along with global trade, has amplified the transmission and zoonotic risk of swine influenza A virus (swIAV). Effective surveillance is essential to uncover emerging virus strains; however gaps remain in our understanding of the swIAV genomic landscape in Southeast Asia.

Electronic Immunoassay Using Enzymatic Metallization on Microparticles.

We present here an inexpensive method for generating a sensitive direct electronic readout in bead-based immunoassays without the use of any intermediate optical instrumentation (e.g., lasers, photomultipliers, etc.

The Lipid Invasion Model: Growing Evidence for This New Explanation of Alzheimer's Disease.

The Lipid Invasion Model (LIM) is a new hypothesis for Alzheimer's disease (AD) which argues that AD is a result of external lipid invasion to the brain, following damage to the blood-brain barrier (BBB). The LIM provides a comprehensive explanation of the observed neuropathologies associated with the disease, including the lipid irregularities first described by Alois Alzheimer himself, and accounts for the wide range of risk factors now identified with AD, all of which are also associated with damage to the BBB. This article summarizes the main arguments of the LIM, and new evidence and arguments in support of it.

Sensitivity and specificity of human point-of-care circulating cathodic antigen (POC-CCA) test in African livestock for rapid diagnosis of schistosomiasis: A Bayesian latent class analysis.

Schistosomiasis is a major neglected tropical disease (NTD) affecting both humans and animals. The morbidity and mortality inflicted upon livestock in the Afrotropical region has been largely overlooked, in part due to a lack of validated sensitive and specific tests, which do not require specialist training or equipment to deliver and interpret. As stressed within the recent WHO NTD 2021-2030 Roadmap and Revised Guideline for schistosomiasis, inexpensive, non-invasive, and sensitive diagnostic tests for livestock-use would also facilitate both prevalence mapping and appropriate intervention programmes.

Simulating contact networks for livestock disease epidemiology: a systematic review.

Contact structure among livestock populations influences the transmission of infectious agents among them. Models simulating realistic contact networks therefore have important applications for generating insights relevant to livestock diseases. This systematic review identifies and compares such models, their applications, data sources and how their validity was assessed.

Method development for the quantification of lead levels in whole blood sampled on Mitra with VAMS tips by inductively coupled plasma-MS/MS.

Lead is harmful for humans by having adverse effects on different biological systems. Venepuncture is the gold standard for blood lead level analysis, but this method has many flaws. The goal of this research was to develop and validate a more practical approach for blood sampling.

Luck perception is associated with less frequent preventive practices and a higher number of social contacts among adults during the SARS-CoV-2 pandemic.

Objectives: Non-pharmaceutical interventions have been crucial to reduce transmission of the SARS-CoV-2 virus in many countries including the United Kingdom. A key research priority has been to better understand psychological and social determinants of health behaviours. We aimed to quantify the impact of luck perception on contact and preventive behaviours among adults in the UK, adjusting for key confounders.

Volumetric Absorptive Microsampling (VAMS) for Targeted LC-MS/MS Determination of Tryptophan-Related Biomarkers.

L-Tryptophan (TRP) metabolites and related biomarkers play crucial roles in physiological functions, and their imbalances are implicated in central nervous system pathologies and neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS), Alzheimer’s disease, Parkinson’s disease, schizophrenia and depression. The measurement of TRP metabolites and related biomarkers possesses great potential to elucidate the disease mechanisms, aid preclinical drug development, highlight potential therapeutic targets and evaluate the outcomes of therapeutic interventions. An effective, straightforward, sensitive and selective liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed for the simultaneous determination of 24 TRP-related compounds in miniaturised murine whole blood samples.

Inflammation and cardiovascular status impact midazolam pharmacokinetics in critically ill children: An observational, prospective, controlled study.

Altered physiology caused by critical illness may change midazolam pharmacokinetics and thereby result in adverse reactions and outcomes in this vulnerable patient population. This study set out to determine which critical illness-related factors impact midazolam pharmacokinetics in children using population modeling. This was an observational, prospective, controlled study of children receiving IV midazolam as part of routine care.

Enhanced Enzymatically Amplified Metallization on Nanostructured Surfaces for Multiplexed Point-of-Care Electrical Detection of COVID-19 Biomarkers.

Inexpensive yet sensitive and specific biomarker detection is a critical bottleneck in diagnostics, monitoring, and surveillance of infectious diseases such as COVID-19. Multiplexed detection of several biomarkers can achieve wider diagnostic applicability, accuracy, and ease-of-use, while reducing cost. Current biomarker detection methods often use enzyme-linked immunosorbent assays (ELISA) with optical detection which offers high sensitivity and specificity.

Exploring why animal health practices are (not) adopted among smallholders in low and middle-income countries: a realist framework and scoping review protocol.

Background: Improving livestock health is considered critical to address poverty, malnutrition and food insecurity in low- and middle-income countries (LMICs). Modifications of livestock management practices is also increasingly recognized as an important strategy to mitigate global threats such as climate change and novel disease emergence. Smallholders are, however, under various constraints which prohibit them from altering health practices for livestock and little is known about how the adoption of these practices may be promoted.

A New Hypothesis for Alzheimer's Disease: The Lipid Invasion Model.

This paper proposes a new hypothesis for Alzheimer's disease (AD)-the lipid invasion model. It argues that AD results from external influx of free fatty acids (FFAs) and lipid-rich lipoproteins into the brain, following disruption of the blood-brain barrier (BBB). The lipid invasion model explains how the influx of albumin-bound FFAs via a disrupted BBB induces bioenergetic changes and oxidative stress, stimulates microglia-driven neuroinflammation, and causes anterograde amnesia.

Incidence and outcomes of post-transplant lymphoproliferative disease after 5365 solid-organ transplants over a 20-year period at two UK transplant centres.

Post-transplant lymphoproliferative disease (PTLD) is a life-threatening complication of solid-organ transplantation (SOT). We present the incidence and outcomes of PTLD in a cohort of 5365 SOT recipients over a 20-year period at two UK transplant centres. With a median follow-up of 7.

Spillover, hybridization, and persistence in schistosome transmission dynamics at the human-animal interface.

Zoonotic spillover and hybridization of parasites are major emerging public and veterinary health concerns at the interface of infectious disease biology, evolution, and control. Schistosomiasis is a neglected tropical disease of global importance caused by parasites of the genus, and the spp. system within Africa represents a key example of a system where spillover of animal parasites into human populations has enabled formation of hybrids.

Volumetric absorptive microsampling: its use in COVID-19 research and testing.

COVID-19 led to changes in the way blood samples are collected. As societies were isolated to control viral spread, access to facilities became limited. Remote sample collection with a volumetric microsampling approach, using Mitra devices based on VAMS technology, proved to be highly effective.

Drivers of zoonotic disease risk in the Indian subcontinent: A scoping review.

Literature on potential anthropogenic drivers of zoonotic disease risk in the Indian subcontinent is sparse. We conducted a scoping review to identify primary sources, published 2000-2020, to clarify what research exists and on which areas future research should focus. We summarised findings thematically by disease.