Preanalytical variables and analytes in liquid biopsy approach for brain tumors: A comprehensive review and recommendations from the RANO Group and the Brain Liquid Biopsy Consortium.

This review explores the pivotal role of preanalytical variables in bringing liquid biopsy approaches into the clinic for brain tumors. Preanalytical variables encompass a range of critical issues, from blood sample collection and handling to the impact of tumor heterogeneity and patient-specific factors. These variables introduce challenges such as false positives, false negatives, and variability in the analysis of tumor signals, which can hinder the diagnostic and prognostic utility of liquid biopsies.

A Review of Focal Therapies for Small Cell Lung Cancer Brain Metastases.

Small cell lung cancer (SCLC) brain metastases (BM) are common at presentation and relapse. Historically, BM were managed with whole brain radiotherapy (WBRT). However, WBRT is associated with significant toxicity, and so interest in the focal management of BM (focal radiotherapy including stereotactic radiosurgery (SRS) and surgery) is increasing.

Resolving anxiety-like behaviour inconsistencies in the elevated plus maze by tracking exploration depth and timing.

The anxiety-like behaviour provoked by the elevated plus maze is primarily measured by the degree to which a rodent explores or avoids the risker, unenclosed arms. Measures such as arm entries and total time spent within the arm are conventionally used, but their analysis often produces inconsistent inferences about the level of anxiety-like behaviour being observed. This inconsistency occurs because the measures do not correlate with one another, raising the question of how validly they capture both the exploratory and avoidance motivations that typify anxiety-like behaviour.

Ocean soundscapes and trends from 2003 to 2021: 10-100 Hz.

We analyze ocean ambient sound from a global network of hydrophones installed and maintained by the Comprehensive Nuclear-Test-Ban Treaty Organization. We process acoustic data from nine hydrophones across six hydroacoustic stations distributed across five oceans: North Pacific, South Pacific, South Atlantic, Indian, and Southern oceans, for up to 19 consecutive years between 2003 and 2021. We identify dominant natural and anthropogenic sources for all six stations and observe long-term trends at four of them.

Milk free of A1 β-casein supports superior gains in cognition and quality of life, relative to conventional milk, in older adults with mild cognitive impairment.

Objectives: To determine whether the regular consumption of milk free from A1 β-casein (A1PF milk) improves cognitive performance to a greater extent than conventional milk, and if so, whether such improvements are associated with an increase in the serum titres of reduced glutathione (GSH).

Design: A multi-centre, double-blind, randomised controlled trial with two parallel arms, conducted from 7 March 2023 to 13 October 2023.

Setting: Two hospitals in Tianjin, China.

Profiling the gut and oral microbiota of hormone receptor-positive, HER2-negative metastatic breast cancer patients receiving pembrolizumab and eribulin.

Changes in host-associated microbial communities (i.e., the microbiota) may modulate responses to checkpoint blockade immunotherapy.

Gut in Tube─Continuous Measurement of Metabolic Crosstalk between Cell Populations in Heterogeneous Samples by NMR Imaging.

In complex living systems, such as the human gut, the interplay between the multiple cell types present is governed by the exchange of small molecule metabolites. However, at present, we lack techniques capable of monitoring this crosstalk in real time and with spatial resolution. Here, we present a model of the human gut in a 5 mm NMR tube that accounts for the intraluminal, mucosal, and colonocyte spaces.

Model-Informed Drug Development of a Sustained Release Formulation of Flucytosine in the Treatment of Cryptococcal Meningitis: A Case Study Using Physiologically Based Pharmacokinetic Modeling.

This paper presents a case study demonstrating the application of model-informed drug development (MIDD) and early modeling integration in the development of a sustained release (SR) formulation of flucytosine for cryptococcal meningoencephalitis (CM) in HIV-infected patients. The study aimed to showcase the value of physiologically based pharmacokinetic (PBPK) modeling and physiologically based biopharmaceutics modeling (PBBM) in guiding decisions and optimizing therapeutic strategies throughout drug development. The MIDD strategy started with a PBPK model based on limited literature data, iteratively refined informed by data from two Phase 1 clinical studies with various flucytosine formulations under different prandial conditions in healthy participants, enhancing model reliability.

Microvascular endothelial cells display organ-specific responses to extracellular matrix stiffness.

The extracellular matrix was originally thought of as simply a cellular scaffold but is now considered a key regulator of cell function and phenotype from which cells can derive biochemical and mechanical stimuli. Age-associated changes in matrix composition drive increases in matrix stiffness. Enhanced matrix stiffness promotes the progression of numerous diseases including cardiovascular disease, musculoskeletal disease, fibrosis, and cancer.

Spatial biology - unravelling complexity within the glioblastoma microenvironment.

The advent and refinement of state-of-the-art spatial biology technologies have facilitated analysis that combines the advantages of high-throughput single cell analysis with techniques that preserve tissue architecture. This combination of cellular phenotyping with retained spatial context provides a much greater understanding of cellular interactions within the tumour microenvironment (TME). For glioblastoma, with its significant intra-tumoural heterogeneity, cellular plasticity, and complex TME, appreciating and understanding these spatial patterns may prove key to improving patient outcomes.

First-Line Chemo-Immunotherapy in SCLC: Outcomes of a Binational Real-World Study.

Introduction: SCLC is characterized by aggressiveness and limited treatment options, especially in extensive-stage SCLC (ES-SCLC). Immunotherapy added to the platinum-etoposide combination has recently become standard in this setting. This retrospective study aims to evaluate the real-world effectiveness of chemo-immunotherapy in patients with ES-SCLC, focusing on subpopulations excluded from clinical trials.

A Breath of Fresh Air: Perspectives on Inhaled Nutrients and Bacteria to Improve Human Health.

We propose that the human respiratory system and olfactory pathways sequester airborne nutrients (vitamins, fatty acids, and trace minerals) that are beneficial for health, which we term "aeronutrients." In addition, airborne bacteria, termed "aeromicrobes," have the potential for positive health effects by improving species diversity in the microbiotas of the respiratory and gastrointestinal tracts. These concepts have implications for people living in urban areas or those who have limited access to nature, such as astronauts exposed for long periods to highly filtered air that may be depleted of aeronutrients and aeromicrobes.

A Triple Mystery of Insidious Organ Failure: Are the Lung, Kidney and Brain All Damaged by the Ageing Pulse?

This review explores the hypothesis that dementia in several forms, chronic kidney disease and idiopathic pulmonary fibrosis have a common cause in pulse-induced capillary haemorrhage. All three conditions are age-related and characterised by insidious onset, uncertainty about their cause, exacerbation by hypertension, resistance to treatment and the relentlessness of their progression. We argue that the three conditions are the clinical outcomes of damage caused by pulse-induced haemorrhage from capillaries.

Effects of Different Cow-Milk Beta-Caseins on the Gut-Brain Axis: A Narrative Review of Preclinical, Animal, and Human Studies.

The gut and brain communicate through bidirectional neural, endocrine, and immune signals to coordinate central nervous system activity with gastrointestinal function. Dysregulated inflammation can promote immune cell activation and increase entero-endocrine signaling and intestinal permeability; hence, a functional gut-brain axis is necessary for a healthy digestive system. The consumption of milk products can lead to gut discomfort via effects on gastrointestinal tract function and the inflammatory state, which, in turn, affect the brain.

A systems genomics and genetics approach to identify the genetic regulatory network for lignin content in seeds.

Seed quality traits of oilseed rape, (), exhibit quantitative inheritance determined by its genetic makeup and the environment via the mediation of a complex genetic architecture of hundreds to thousands of genes. Thus, instead of single gene analysis, network-based systems genomics and genetics approaches that combine genotype, phenotype, and molecular phenotypes offer a promising alternative to uncover this complex genetic architecture. In the current study, systems genetics approaches were used to explore the genetic regulation of lignin traits in seeds.

A proteomics approach to isolating neuropilin-dependent α5 integrin trafficking pathways: neuropilin 1 and 2 co-traffic α5 integrin through endosomal p120RasGAP to promote polarised fibronectin fibrillogenesis in endothelial cells.

Integrin trafficking to and from membrane adhesions is a crucial mechanism that dictates many aspects of a cell's behaviour, including motility, polarisation, and invasion. In endothelial cells (ECs), the intracellular traffic of α5 integrin is regulated by both neuropilin 1 (NRP1) and neuropilin 2 (NRP2), yet the redundancies in function between these co-receptors remain unclear. Moreover, the endocytic complexes that participate in NRP-directed traffic remain poorly annotated.

A brain metastasis liquid biopsy: Where are we now?

Brain metastases remain a challenging and feared complication for patients with cancer and research in this area has lagged behind research into metastases to other organs. Due to their location and the risks associated with neurosurgical biopsies, the biology underpinning brain metastases response to treatment and evolution over time remains poorly understood. Liquid biopsies are proposed to overcome many of the limitations present with tissue biopsies, providing a better representation of tumor heterogeneity, facilitating repeated sampling, and providing a noninvasive assessment of tumor biology.

Practical Synthesis of 6-Amino-1-hydroxy-2,1-benzoxaborolane: A Key Intermediate of DNDI-6148.

Visceral leishmaniasis (VL), a parasitic, poverty-linked, neglected disease, is endemic across multiple regions of the world and fatal if untreated. There is an urgent need for a better and more affordable treatment for VL. DNDI-6148 is a promising drug candidate being evaluated for the treatment of VL; however, the current process for producing the key intermediate of DNDI-6148, 6-amino-1-hydroxy-2,1-benzoxaborolane, is expensive and difficult to scale up.

Alternative donor transplantation for severe aplastic anemia: a comparative study of the SAAWP EBMT.

Selecting the most suitable alternative donor becomes challenging in severe aplastic anemia (SAA) when a matched sibling donor (MSD) is unavailable. We compared outcomes in patients with SAA undergoing stem cell transplantation (SCT) from matched unrelated donors (MUD) (n = 1106), mismatched unrelated donors (MMUD) (n = 340), and haploidentical donors (Haplo) (n = 206) registered in the European Society for Blood and Marrow Transplantation database (2012-2021). For Haplo SCT, only those receiving posttransplant cyclophosphamide for graft-versus-host disease (GVHD) prophylaxis were included.

Management of glioblastoma in elderly patients: A review of the literature.

High grade gliomas are the most common primary aggressive brain tumours with a very poor prognosis and a median survival of less than 2 years. The standard management protocol of newly diagnosed glioblastoma patients involves surgery followed by radiotherapy, chemotherapy in the form of temozolomide and further adjuvant temozolomide. The recent advances in molecular profiling of high-grade gliomas have further enhanced our understanding of the disease.

Treosulfan compared to busulfan in allogeneic haematopoietic stem cell transplantation for myelofibrosis: a registry-based study from the Chronic Malignancies Working Party of the EBMT.

We aimed to compare outcomes following treosulfan (TREO) or busulfan (BU) conditioning in a large cohort of myelofibrosis (MF) patients from the EBMT registry. A total of 530 patients were included; 73 received TREO and 457 BU (BU ≤ 6.4 mg/kg in 134, considered RIC, BU > 6.

Bioavailability of three novel oral, sustained-release pellets, relative to an immediate-release tablet containing 500 mg flucytosine: A randomized, open-label, crossover study in healthy volunteers.

The opportunistic fungal infection cryptococcal meningoencephalitis is a major cause of death among people living with HIV in sub-Saharan Africa. We report pharmacokinetic (PK) and safety data from a randomized, four-period crossover phase I trial of three sustained-release (SR) oral pellet formulations of 5-flucytosine conducted in South Africa. These formulations were developed to require less frequent administration, to provide a convenient alternative to the current immediate release (IR) formulation, A.

Interrelatedness of steering and lateral position parameters: Recommendations for the assessment of driving performance.

Introduction: Loss of attention leads to less steady driving within the lane and is one of the main causes of road accidents. To improve road safety, vehicle-based parameters such as steering wheel angle and lateral position are used to objectively assess driving performance, especially in monotonous driving tasks.

Method: The present driving simulator study investigated the extent to which eight commonly used parameters are independent indicators of driving performance.