From Pulses to Sleep Stages: Towards Optimized Sleep Classification Using Heart-Rate Variability.

More and more people quantify their sleep using wearables and are becoming obsessed in their pursuit of optimal sleep ("orthosomnia"). However, it is criticized that many of these wearables are giving inaccurate feedback and can even lead to negative daytime consequences. Acknowledging these facts, we here optimize our previously suggested sleep classification procedure in a new sample of 136 self-reported poor sleepers to minimize erroneous classification during ambulatory sleep sensing.

The impact of vaccine-linked chemotherapy on liver health in a mouse model of chronic Trypanosoma cruzi infection.

Background: Chagas disease, chronic infection with Trypanosoma cruzi, mainly manifests as cardiac disease. However, the liver is important for both controlling parasite burdens and metabolizing drugs. Notably, high doses of anti-parasitic drug benznidazole (BNZ) causes liver damage.

Review of flow cytometry as a tool for cell and gene therapy.

Quality control testing and analytics are critical for the development and manufacture of cell and gene therapies, and flow cytometry is a key quality control and analytical assay that is used extensively. However, the technical scope of characterization assays and safety assays must keep apace as the breadth of cell therapy products continues to expand beyond hematopoietic stem cell products into producing novel adoptive immune therapies and gene therapy products.  Flow cytometry services are uniquely positioned to support the evolving needs of cell therapy facilities, as access to flow cytometers, new antibody clones and improved fluorochrome reagents becomes more egalitarian.

Localized cardiac small molecule trajectories and persistent chemical sequelae in experimental Chagas disease.

Post-infectious conditions present major health burdens but remain poorly understood. In Chagas disease (CD), caused by Trypanosoma cruzi parasites, antiparasitic agents that successfully clear T. cruzi do not always improve clinical outcomes.

Global regulatory reforms to promote equitable vaccine access in the next pandemic.

There is broad consensus that the global response to the Covid-19 pandemic was inadequate, leading to unacceptable levels of avoidable morbidity and mortality. Three strategic missteps led to the lack of equitable vaccine access: The heavy reliance on commercial vaccine manufacturers in high-income countries (HICs) versus low- and middle-income countries (LMICs); the emergence of vaccine nationalism restricting and delaying the supply of vaccines to LMICs; and an inadequate support or recognition for LMIC national regulatory authorities. To avoid these inequities in a future pandemic, we focus on three successful vaccine development and technology transfer case studies-the Hepatitis B vaccine produced in South Korea in the 1980s; the Meningitis A vaccine for Africa led by Program for Appropriate Technologies in Health (PATH) and the World Health Organization (WHO) in the 2000s; and a recombinant SARS CoV-2 protein-based vaccine technology from the Texas Children's Hospital transferred to India and to Indonesia.

Association Between Prescription Drug Discount Cards and Out-of-Pocket Costs for HFrEF Regimens.

Background: The burden from medication costs for treating heart failure can be financially toxic for uninsured/underinsured patients and their families. Prescription discount cards, which offer cash price reductions, may decrease out-of-pocket costs for patients without prescription benefits, but the degree to which they offer financial relief remains unclear. Our objective was to assess the financial burden for uninsured/underinsured patients prescribed a drug from each of the 4 standard classes of medications for heart failure with reduced ejection fraction.

Association of EEG Background and Neurodevelopmental Outcome in Neonates With Hypoxic-Ischemic Encephalopathy Receiving Hypothermia.

Background And Objectives: Predicting neurodevelopmental outcome for neonates with hypoxic-ischemic encephalopathy (HIE) is important for clinical decision-making, care planning, and parent communication. We examined the relationship between EEG background and neurodevelopmental outcome among children enrolled in a trial of erythropoietin or placebo for neonates with HIE treated with therapeutic hypothermia.

Methods: Participants had EEG recorded throughout hypothermia.

Neutrophil extracellular traps induce persistent lung tissue damage via thromboinflammation without altering virus resolution in a mouse coronavirus model.

Background: During infection, neutrophil extracellular traps (NETs) are associated with severity of pulmonary diseases such as acute respiratory disease syndrome. NETs induce subsequent immune responses, are directly cytotoxic to pulmonary cells, and are highly procoagulant. Anticoagulation treatment was shown to reduce in-hospital mortality, indicating thromboinflammatory complications.

The combination of PAC-1 and entrectinib for the treatment of metastatic uveal melanoma.

The treatment of metastatic uveal melanoma remains a major clinical challenge. Procaspase-3, a proapoptotic protein and precursor to the key apoptotic executioner caspase-3, is overexpressed in a wide range of malignancies, and the drug PAC-1 leverages this overexpression to selectively kill cancer cells. Herein, we investigate the efficacy of PAC-1 against uveal melanoma cell lines and report the synergistic combination of PAC-1 and entrectinib.

Method for efficient calculating earth pressure of retaining wall considering plant transpiration.

An accurate estimation of earth pressure on retaining walls is imperative to achieving its design. This paper presents an analytical method framework that considers the effect of plant transpiration relative to the traditional calculation approaches. Specifically, a closed-form solution for one-dimensional steady unsaturated flow considering plant transpiration is incorporated into a representation of effective stress to obtain the changes in matric suction, and effective stress.

Correlating Quantitative MRI-based Apparent Diffusion Coefficient Metrics with 24-month Neurodevelopmental Outcomes in Neonates from the HEAL Trial.

Background Multiple qualitative scoring systems have been created to capture the imaging severity of hypoxic ischemic brain injury. Purpose To evaluate quantitative volumes of acute brain injury at MRI in neonates with hypoxic ischemic brain injury and correlate these findings with 24-month neurodevelopmental outcomes and qualitative brain injury scoring by radiologists. Materials and Methods In this secondary analysis, brain diffusion-weighted MRI data from neonates in the High-dose Erythropoietin for Asphyxia and Encephalopathy trial, which recruited participants between January 2017 and October 2019, were analyzed.

The Insertion of an Evolutionary Lost Four-Amino-Acid Cytoplasmic Tail Peptide into a Syncytin-1 Vaccine Increases T- and B-Cell Responses in Mice.

Human endogenous retrovirus type W (HERV-W) is expressed in various cancers. We previously developed an adenovirus-vectored cancer vaccine targeting HERV-W by encoding an assembled HERV-W group-specific antigen sequence and the HERV-W envelope sequence Syncytin-1. Syncytin-1 is constitutively fusogenic and forms large multinucleated cell fusions when overexpressed.

Imaging of cell death in malignancy: Targeting pathways or phenotypes?

Cell death is fundamental in health and disease and resisting cell death is a hallmark of cancer. Treatment of malignancy aims to cause cancer cell death, however current clinical imaging of treatment response does not specifically image cancer cell death but assesses this indirectly either by changes in tumor size (using x-ray computed tomography) or metabolic activity (using 2-[F]fluoro-2-deoxy-glucose positron emission tomography). The ability to directly image tumor cell death soon after commencement of therapy would enable personalised response adapted approaches to cancer treatment that is presently not possible with current imaging, which is in many circumstances neither sufficiently accurate nor timely.

Phase I dose-escalation study of procaspase-activating compound-1 in combination with temozolomide in patients with recurrent high-grade astrocytomas.

Background: Procaspase-3 (PC-3) is overexpressed in various tumor types, including gliomas. Targeted PC-3 activation combined with chemotherapy is a novel strategy for treating patients with high-grade gliomas, with promising preclinical activity. This study aimed to define safety and tolerability of procaspase-activating compound-1 (PAC-1) in combination with temozolomide (TMZ) for patients with recurrent high-grade astrocytomas.

Heterologous mRNA-protein vaccination with Tc24 induces a robust cellular immune response against , characterized by an increased level of polyfunctional CD8 T-cells.

Tc24 is a derived flagellar protein that, when formulated with a TLR-4 agonist adjuvant, induces a balanced immune response in mice, elevating IgG2a antibody titers and IFN-γ levels. Furthermore, vaccination with the recombinant Tc24 protein can reduce parasite levels and improve survival during acute infection. Although some mRNA vaccines have been proven to elicit a stronger immune response than some protein vaccines, they have not been used against .

Plasma Membrane Channel TRPM4 Mediates Immunogenic Therapy-Induced Necrosis.

Unlabelled: Several emerging therapies kill cancer cells primarily by inducing necrosis. As necrosis activates immune cells, potentially, uncovering the molecular drivers of anticancer therapy-induced necrosis could reveal approaches for enhancing immunotherapy efficacy. To identify necrosis-associated genes, we performed a genome-wide CRISPR-Cas9 screen with negative selection against necrosis-inducing preclinical agents BHPI and conducted follow-on experiments with ErSO.

A Novel, Precise and High-Throughput Technology for Viroid Detection in Cannabis (MFDetect).

Hop latent viroid (HLVd) is a severe disease of cannabis, causing substantial economic losses in plant yield and crop value for growers worldwide. The best way to control the disease is early detection to limit the spread of the viroid in grow facilities. This study describes MFDetect as a rapid, highly sensitive, and high-throughput tool for detecting HLVd in the early stages of plant development.

Minimally Invasive Postero-Inferior Sacroiliac Joint Fusion: Surgical Technique and Procedural Details.

(1) Background: Minimally invasive sacroiliac joint (SIJ) fusion is the preferred surgical intervention to treat chronically severe pain associated with SIJ degeneration and dysfunction. (2) Methods: This paper details the ten-step surgical procedure associated with the postero-inferior approach using the PsiF™ DNA Sacroiliac Joint Fusion System. (3) Results: The posterior surgical approach with an inferior operative trajectory (postero-inferior) utilizes easily identifiable landmarks to provide the safest, most direct access to the articular joint space for transfixing device placement.

The impact of vaccine-linked chemotherapy on liver health in a mouse model of chronic infection.

Background: Chagas disease, chronic infection with , mainly manifests as cardiac disease. However, the liver is important for both controlling parasite burdens and metabolizing drugs. Notably, high doses of anti-parasitic drug benznidazole (BNZ) causes liver damage.

Management of multiple myeloma-related renal impairment: recommendations from the International Myeloma Working Group.

Here, the International Myeloma Working Group (IMWG) updates its clinical practice recommendations for the management of multiple myeloma-related renal impairment on the basis of data published until Dec 31, 2022. All patients with multiple myeloma and renal impairment should have serum creatinine, estimated glomerular filtration rate, and free light chains (FLCs) measurements together with 24-h urine total protein, electrophoresis, and immunofixation. If non-selective proteinuria (mainly albuminuria) or involved serum FLCs value less than 500 mg/L is detected, then a renal biopsy is needed.

Shared genetic etiology between ADHD, task-related behavioral measures and brain activation during response inhibition in a youth ADHD case-control study.

Impaired response inhibition is commonly present in individuals with attention-deficit/hyperactivity disorder (ADHD) and their unaffected relatives, suggesting impaired response inhibition as a candidate endophenotype in ADHD. Therefore, we explored whether behavioral and neural correlates of response inhibition are related to polygenic risk scores for ADHD (PRS-ADHD). We obtained functional magnetic resonance imaging of neural activity and behavioral measures during a stop-signal task in the NeuroIMAGE cohort, where inattention and hyperactivity-impulsivity symptoms were assessed with the Conners Parent Rating Scales.