Coordinated immune networks in leukemia bone marrow microenvironments distinguish response to cellular therapy.

Understanding how intratumoral immune populations coordinate antitumor responses after therapy can guide treatment prioritization. We systematically analyzed an established immunotherapy, donor lymphocyte infusion (DLI), by assessing 348,905 single-cell transcriptomes from 74 longitudinal bone marrow samples of 25 patients with relapsed leukemia; a subset was evaluated by both protein- and transcriptome-based spatial analysis. In acute myeloid leukemia (AML) DLI responders, we identified clonally expanded CD8 cytotoxic T lymphocytes with in vitro specificity for patient-matched AML.

VNS paired with training enhances recognition memory: mechanistic insights from proteomic analysis of the hippocampal synapse.

Introduction: Recognition memory, an essential component of cognitive health, can suffer from biological limitations of stress, aging, or neurodegenerative disease. Vagus nerve stimulation (VNS) is a neuromodulation therapy with the potential to improve cognitive function. This study investigated the effectiveness of multiple sessions of VNS to enhance recognition memory in healthy rodents and the underlying cognitive benefits of VNS by proteomic analysis of the synaptosome.

Building a holistic health approach in supported housing for people with intellectual disabilities in Denmark.

People with intellectual disabilities (IDs) face health issues and barriers to physical activity. Health promotion programmes targeting this group are often short-term. Few programmes have been designed for people with IDs who live in supported housing staffed by social care workers (SCWs).

Ancient genomics support deep divergence between Eastern and Western Mediterranean Indo-European languages.

The Indo-European languages are among the most widely spoken in the world, yet their early diversification remains contentious. It is widely accepted that the spread of this language family across Europe from the 5th millennium BP correlates with the expansion and diversification of steppe-related genetic ancestry from the onset of the Bronze Age. However, multiple steppe-derived populations co-existed in Europe during this period, and it remains unclear how these populations diverged and which provided the demographic channels for the ancestral forms of the Italic, Celtic, Greek, and Armenian languages.

The antitumor activity of TGFβ-specific T cells is dependent on IL-6 signaling.

Although interleukin (IL)-6 is considered immunosuppressive and tumor-promoting, emerging evidence suggests that it may support antitumor immunity. While combining immune checkpoint inhibitors (ICIs) and radiotherapy in patients with pancreatic cancer (PC) has yielded promising clinical results, the addition of an anti-IL-6 receptor (IL-6R) antibody has failed to elicit clinical benefits. Notably, a robust TGFβ-specific immune response at baseline in PC patients treated solely with ICIs and radiotherapy correlated with improved survival.

Genome-based newborn screening for severe childhood genetic diseases has high positive predictive value and sensitivity in a NICU pilot trial.

Large prospective clinical trials are underway or planned that examine the clinical utility and cost effectiveness of genome-based newborn screening (gNBS). One gNBS platform, BeginNGS, currently screens 53,575 variants for 412 severe childhood genetic diseases with 1,603 efficacious therapies. Retrospective evaluation of BeginNGS in 618,290 subjects suggests adequate sensitivity and positive predictive value (PPV) to proceed to prospective studies.

Prequalification of genome-based newborn screening for severe childhood genetic diseases through federated training based on purifying hyperselection.

Genome-sequence-based newborn screening (gNBS) has substantial potential to improve outcomes in hundreds of severe childhood genetic disorders (SCGDs). However, a major impediment to gNBS is imprecision due to variants classified as pathogenic (P) or likely pathogenic (LP) that are not SCGD causal. gNBS with 53,855 P/LP variants, 342 genes, 412 SCGDs, and 1,603 therapies was positive in 74% of UK Biobank (UKB470K) adults, suggesting 97% false positives.

Microstructure competences and grammatical errors of Danish-speaking children with developmental language disorder when telling and retelling narratives and engaging in spontaneous language.

Background: Research on the grammatical characteristics of children with developmental language disorder (DLD) across languages has challenged accounts about the nature of DLD. Studies of the characteristics of DLD in different languages can reveal which components of DLD emerge irrespective of language and which components are language specific.

Aims: To examine the grammatical characteristics of children with DLD acquiring Danish (microstructure and error types) in order to contribute to research on language-general and language-specific characteristics of DLD.

Cluster perturbation theory. X. A parallel implementation of Lagrangian perturbation series for the coupled cluster singles and doubles ground-state energy through fifth order.

We describe an efficient implementation of cluster perturbation and Møller-Plesset Lagrangian energy series through the fifth order that targets the coupled cluster singles and doubles energy utilizing the resolution of the identity approximation. We illustrate the computational performance of the implementation by performing ground state energy calculations on systems with up to 1200 basis functions using a single node and by comparison to conventional coupled cluster singles and doubles calculations. We further show that our hybrid message passing interface/open multiprocessing parallel implementation that also utilizes graphical processing units can be used to obtain fifth order energies on systems with almost 1200 basis functions with a 90 min "time to solution" running on Frontier at Oak Ridge National Laboratory.

Sedation and general anaesthesia of crocodilians: a systematic review.

Sedation and general anaesthesia of crocodilians pose unique challenges due to their aggressive nature, poikilothermic physiology, and specific anatomical and physiological characteristics, all factors that complicate crocodilian anaesthesia. This review aimed to systematically review the literature regarding sedation and general anaesthesia of crocodilians with focus on efficacy and impact on vital parameters. A systematic literature search was performed according to PRISMA guidelines on May 2, 2023 in the databases Embase, PubMed, Scopus and Web of Science.

Ensuring High Quality Treatment Plans with a Plan Quality Review Checklist.

Treatment plan quality is a crucial component for a successful outcome of radiation therapy treatments. As the complexity of radiation therapy planning and delivery techniques increases, the role of the medical physicist in assessing treatment plan quality becomes more critical. Integrating plan quality review throughout the treatment planning process allows improvements without delaying treatment or rushing to produce changes at the last minute.

Putting computational models of immunity to the test - an invited challenge to predict vaccination outcomes.

Systems vaccinology studies have been used to build computational models that predict individual vaccine responses and identify the factors contributing to differences in outcome. Comparing such models is challenging due to variability in study designs. To address this, we established a community resource to compare models predicting booster responses and generate experimental data for the explicit purpose of model evaluation.

From Inception to Malignancy: the Co-evolution of Pancreatic Cancer and Its Immunosuppressive Microenvironment.

Published in Cancer Research in 2007, Clark and colleagues first introduced the concept that the immune microenvironment evolves in lockstep with the progression of pancreatic cancer. Leveraging genetically engineered mouse models of the disease that were described a few years earlier, Clark and colleagues used a combination of approaches to describe the dynamics of immune evolution in precursor lesions all the way to overt malignancy. They discovered that immunosuppression is established at the earliest stages of carcinogenesis.

Investigating Lipase/Stain Interactions: Determining Interfacial Protein Conformation with Surface Spectroscopy.

Conventional bulk protein structure determination methods are not suitable for understanding the distinct and diverse interactions of proteins with interfaces. Notably, interfacial activation is a feature common to many lipases involving movement of a helical "lid" region upon contact with a hydrophobic surface to expose the catalytic site. Here we use the surface specificity of vibrational sum frequency generation spectroscopy (VSFG) spectroscopy to directly probe the conformation of lipase (TLL) at hydrophobic interfaces.

Nature-Based Therapeutic Intervention for Individuals with Post-Concussion Symptoms.

This study investigated the efficacy of a 10-session nature-based therapeutic intervention for people with post-concussion symptoms. The intervention involved physical and vestibular exercises, sensory training, relaxation, and psychoeducation, all of which were integrated with the natural environment in a forest therapy garden. This study was designed with a passive control period followed by the intervention ( = 30).

On the coupling of intracellular to glycolytic oscillations in yeast.

We have investigated the interplay between glycolytic oscillations and intracellular concentration in the yeast Saccharomyces cerevisiae. Intracellular concentration was measured using the fluorophore potassium-binding benzofuranisophthalate (PBFI). We found that is an essential ion for the occurrence of glycolytic oscillations and that intracellular concentration oscillates synchronously with other variables such as nicotinamide adenine dinucleotide hydride (NADH), intracellular adenosine triphosphate (ATP), and mitochondrial membrane potential.

Clinical segmentation in 22q11.2 deletion syndrome: Cognitive impairments and additional genetic load.

The 22q11.2 deletion syndrome (22q11.2DS) is associated with high psychiatric morbidity.

Posttraumatic Arthritis Is More Common in Patients Undergoing Total Knee Arthroplasty Before Age 50.

Primary total knee arthroplasty (TKA) in patients under 50 is becoming more common. The goal of this study was to identify the diagnoses and predisposing factors for TKA prior to age 50. The Military Data Repository was queried for patients undergoing TKA prior to age 50.

Glycolysis inhibition affects proliferation and cytotoxicity of Vγ9Vδ2 T cells expanded for adoptive cell therapy.

Background Aims: Vγ9Vδ2 T cells are under investigation as alternative effector cells for adoptive cell therapy (ACT) in cancer. Despite promising in vitro results, anti-tumor efficacies in early clinical studies have been lower than expected, which could be ascribed to the complex interplay of tumor and immune cell metabolism competing for the same nutrients in the tumor microenvironment.

Methods: To contribute to the scarce knowledge regarding gamma delta T-cell metabolism, we investigated the metabolic phenotype of 25-day-expanded Vγ9Vδ2 T cells and how it is intertwined with functionality.

Developing a survey to measure nursing students' knowledge, attitudes and beliefs, influences, and willingness to be involved in Medical Assistance in Dying (MAiD): a mixed method modified e-Delphi study.

Background: Medical Assistance in Dying (MAiD) was legalized in Canada in 2016. Canada's legislation is the first to permit Nurse Practitioners (NP) to serve as independent MAiD assessors and providers. Registered Nurses' (RN) also have important roles in MAiD that include MAiD care coordination; client and family teaching and support, MAiD procedural quality; healthcare provider and public education; and bereavement care for family.

Stress-free blood sampling in minipigs: A novel method for assessing 24-h cortisol profiles and drug effects on diurnal and ultradian rhythms.

We developed a novel, stress-free blood sampling method for minipigs, allowing continuous cortisol monitoring over 24 h. Baseline cortisol levels exhibited both ultradian and diurnal rhythms. During nighttime, smaller ultradian rhythms overlaid a lower baseline cortisol, which increased in sleeping pigs before lights were turned on.