Systems biology-enabled targeting of NF-κB and BCL2 overcomes microenvironment-mediated BH3-mimetic resistance in DLBCL.

Unlabelled: In Diffuse Large B-cell Lymphoma (DLBCL), elevated anti-apoptotic BCL2-family proteins (e.g., MCL1, BCL2, BCLXL) and NF-κB subunits (RelA, RelB, cRel) confer poor prognosis.

Joint position statement on immersion pulmonary oedema and diving from the South Pacific Underwater Medicine Society (SPUMS) and the United Kingdom Diving Medical Committee (UKDMC) 2024.

This joint position statement (JPS) on immersion pulmonary oedema (IPO) and diving is the product of a workshop held at the 52nd Annual Scientific Meeting of the South Pacific Underwater Medicine Society (SPUMS) from 12-17 May 2024, and consultation with the United Kingdom Diving Medical Committee (UKDMC), three members of which attended the meeting. The JPS is a consensus of experts with relevant evidence cited where available. The statement reviews the nomenclature, pathophysiology, risk factors, clinical features, prehospital treatment, investigation of and the fitness for future compressed gas diving following an episode of IPO.

Divers treated in Townsville, Australia: worse symptoms lead to poorer outcomes.

Introduction: Hyperbaric oxygen treatment (HBOT) is considered definitive treatment for decompression illness. Delay to HBOT may be due to dive site remoteness and limited facility availability. Review of cases may help identify factors contributing to clinical outcomes.

Patient-specific computational models predict prognosis in B cell lymphoma by quantifying pro-proliferative and anti-apoptotic signatures from genetic sequencing data.

Genetic heterogeneity and co-occurring driver mutations impact clinical outcomes in blood cancers, but predicting the emergent effect of co-occurring mutations that impact multiple complex and interacting signalling networks is challenging. Here, we used mathematical models to predict the impact of co-occurring mutations on cellular signalling and cell fates in diffuse large B cell lymphoma and multiple myeloma. Simulations predicted adverse impact on clinical prognosis when combinations of mutations induced both anti-apoptotic (AA) and pro-proliferative (PP) signalling.

Which Ultrasound Characteristics Predict Lymphatic Spread of Papillary Thyroid Cancer?

Introduction: The 2015 American Thyroid Association guidelines recommend lymph node mapping US in patients with definitive cytological evidence of thyroid cancer. Suspicious lymph node features on imaging including enlarged size (>1 cm in any dimension), architectural distortion, loss of fatty hilum, and microcalcifications often prompt evaluation with fine needle aspiration. There is no universally agreed upon model for determining which ultrasound characteristics most strongly correlate with metastatic disease.

Decompression illness: a comprehensive overview.

Decompression illness is a collective term for two maladies (decompression sickness [DCS] and arterial gas embolism [AGE]) that may arise during or after surfacing from compressed gas diving. Bubbles are the presumed primary vector of injury in both disorders, but the respective sources of bubbles are distinct. In DCS bubbles form primarily from inert gas that becomes dissolved in tissues over the course of a compressed gas dive.

The first deep rebreather dive using hydrogen: case report.

Bounce diving with rapid descents to very deep depths may provoke the high-pressure neurological syndrome (HPNS). The strategy of including small fractions of nitrogen in the respired gas to produce an anti-HPNS narcotic effect increases the gas density which may exceed recommended guidelines. In 2020 the 'Wetmules' dive team explored the Pearse Resurgence cave (New Zealand) to 245 m breathing trimix (approximately 4% oxygen, 91% helium and 5% nitrogen).

Propagating variational model uncertainty for bioacoustic call label smoothing.

Along with propagating the input toward making a prediction, Bayesian neural networks also propagate uncertainty. This has the potential to guide the training process by rejecting predictions of low confidence, and recent variational Bayesian methods can do so without Monte Carlo sampling of weights. Here, we apply sample-free methods for wildlife call detection on recordings made via passive acoustic monitoring equipment in the animals' natural habitats.

Comparing the EMMA capnograph with sidestream capnography and arterial carbon dioxide pressure at 284 kPa.

Introduction: Capnography aids assessment of the adequacy of mechanical patient ventilation. Physical and physiological changes in hyperbaric environments create ventilation challenges which make end-tidal carbon dioxide (ETCO) measurement particularly important. However, obtaining accurate capnography in hyperbaric environments is widely considered difficult.

Full-face snorkel masks increase the incidence of hypoxaemia and hypercapnia during simulated snorkelling compared to conventional snorkels.

Introduction: Air flow in full-face snorkel masks (FFSMs) should be unidirectional to prevent rebreathing of exhaled air. This study evaluated rebreathing and its consequences when using FFSMs compared to a conventional snorkel.

Methods: In a dry environment 20 participants wore three types of snorkel equipment in random order: Subea Easybreath FFSM; QingSong 180-degree panoramic FFSM; and a Beuchat Spy conventional snorkel (with nose clip), in three conditions: rest in a chair; light; and moderate intensity exercise on a cycle ergometer.

A systematic review of electroencephalography in acute cerebral hypoxia: clinical and diving implications.

Introduction: Hypoxia can cause central nervous system dysfunction and injury. Hypoxia is a particular risk during rebreather diving. Given its subtle symptom profile and its catastrophic consequences there is a need for reliable hypoxia monitoring.

Rebreather Forum Four consensus statements.

Closed circuit rebreathers have been widely adopted by technical divers as tools for reducing gas consumption and extending depth and duration capabilities. Rebreathers are technologically complex with many failure points, and their use appears associated with a higher accident rate than open circuit scuba. Rebreather Forum Four (RF4) was held in Malta in April 2023 attracting approximately 300 attendees and representatives of multiple manufacturers and training agencies.

NF-κB fingerprinting reveals heterogeneous NF-κB composition in diffuse large B-cell lymphoma.

Introduction: Improving treatments for Diffuse Large B-Cell Lymphoma (DLBCL) is challenged by the vast heterogeneity of the disease. Nuclear factor-κB (NF-κB) is frequently aberrantly activated in DLBCL. Transcriptionally active NF-κB is a dimer containing either RelA, RelB or cRel, but the variability in the composition of NF-κB between and within DLBCL cell populations is not known.

Computational modeling of DLBCL predicts response to BH3-mimetics.

In healthy cells, pro- and anti-apoptotic BCL2 family and BH3-only proteins are expressed in a delicate equilibrium. In contrast, this homeostasis is frequently perturbed in cancer cells due to the overexpression of anti-apoptotic BCL2 family proteins. Variability in the expression and sequestration of these proteins in Diffuse Large B cell Lymphoma (DLBCL) likely contributes to variability in response to BH3-mimetics.

NF-kB and the CLL microenvironment.

Chronic lymphocytic leukemia (CLL) is the most prevalent type of leukemia in the western world. Despite the positive clinical effects of new targeted therapies, CLL still remains an incurable and refractory disease and resistance to treatments are commonly encountered. The Nuclear Factor-Kappa B (NF-κB) transcription factor has been implicated in the pathology of CLL, with high levels of NF-κB associated with disease progression and drug resistance.

The NF-κB multidimer system model: A knowledge base to explore diverse biological contexts.

The nuclear factor κB (NF-κB) system is critical for various biological functions in numerous cell types, including the inflammatory response, cell proliferation, survival, differentiation, and pathogenic responses. Each cell type is characterized by a subset of 15 NF-κB dimers whose activity is regulated in a stimulus-responsive manner. Numerous studies have produced different mathematical models that account for cell type-specific NF-κB activities.

Logged tropical forests have amplified and diverse ecosystem energetics.

Old-growth tropical forests are widely recognized as being immensely important for their biodiversity and high biomass. Conversely, logged tropical forests are usually characterized as degraded ecosystems. However, whether logging results in a degradation in ecosystem functions is less clear: shifts in the strength and resilience of key ecosystem processes in large suites of species have rarely been assessed in an ecologically integrated and quantitative framework.

Safeguarding Imperiled Biodiversity and Evolutionary Processes in the Wallacea Center of Endemism.

Wallacea-the meeting point between the Asian and Australian fauna-is one of the world's largest centers of endemism. Twenty-three million years of complex geological history have given rise to a living laboratory for the study of evolution and biodiversity, highly vulnerable to anthropogenic pressures. In the present article, we review the historic and contemporary processes shaping Wallacea's biodiversity and explore ways to conserve its unique ecosystems.

Does hyperbaric oxygen cause narcosis or hyperexcitability? A quantitative EEG analysis.

Divers breathe higher partial pressures of oxygen at depth than at the surface. The literature and diving community are divided on whether or not oxygen is narcotic. Conversely, hyperbaric oxygen may induce dose-dependent cerebral hyperexcitability.

Extended lifetimes of bubbles at hyperbaric pressure may contribute to inner ear decompression sickness during saturation diving.

Inner ear decompression sickness (IEDCS) may occur after upward or downward excursions in saturation diving. Previous studies in nonsaturation diving strongly suggest that IEDCS is caused by arterialization of small venous bubbles across intracardiac or intrapulmonary right-to-left shunts and bubble growth through inward diffusion of supersaturated gas when they arrive in the inner ear. The present study used published saturation diving data and models of inner ear inert gas kinetics and bubble dynamics in arterial conditions to assess whether IEDCS after saturation excursions could also be explained by arterialization of venous bubbles and whether such bubbles might survive longer and be more likely to reach the inner ear under deep saturation diving conditions.

Comment on Mankowska et al. Critical Flicker Fusion Frequency: A Narrative Review. 2021, , 1096.

We have read with great interest the review by Mankowska et al. [..