Stem Loop Mediated Transgene Modulation in Human T Cells.

Controlling gene expression is useful for many applications, but current methods often require external user inputs, such as the addition of a drug. We present an alternative approach using cell-autonomous triggers based on RNA stem loop structures in the 3' untranslated regions (UTRs) of mRNA. These stem loops are targeted by the RNA binding proteins Regnase-1 and Roquin-1, allowing us to program stimulation-induced transgene regulation in primary human T cells.

Association between dietary inflammatory index score and incident dementia.

Introduction: We evaluated whether higher Dietary Inflammatory Index (DII) scores were associated with increased incidence of all-cause dementia and Alzheimer's disease (AD) dementia over 22.3 years of follow-up in the community-based Framingham Heart Study Offspring cohort.

Methods: One thousand four hundred eighty-seven participants (mean ± standard deviation, age in years 69 ± 6) completed food frequency questionnaires (FFQs) and had incident all-cause dementia and AD surveillance data available.

Defining health equity: A modern US perspective.

Health equity is a concept that has gained increasing attention and relevance in the context of the COVID-19 pandemic, which has exposed and exacerbated the health disparities and inequities among different population groups in the United States. This article aims to provide a comprehensive and critical overview of the historical, theoretical, and empirical foundations of health equity, as well as the challenges and opportunities for advancing it in the modern US society. By adopting an interdisciplinary and intersectional approach, and by drawing on literature from public health, sociology, economics, and human rights, we argue that health equity is not only a matter of fairness and justice, but also a strategic and pragmatic goal for improving the health and well-being of the entire nation.

Global epidemiology of serogroup Y invasive meningococcal disease: a literature review.

Serogroup epidemiology of invasive meningococcal disease (IMD) is constantly evolving, varying by time and location. Surveillance reports have indicated a rise in meningococcal serogroup Y (MenY) in some regions in recent years. This systematic literature review explores the evolving epidemiology of MenY IMD globally based on review of recent articles and national surveillance reports published between 1 January 2010 and 25 March 2021.

Anterior-to-Central Cartilage Defects of Arthritic Knee Showed Better Cartilage Regeneration Than Posterior Cartilage Defects Using Mesenchymal Stem Cell Implantation.

Purpose: To analyze cartilage regeneration and clinical outcomes after human umbilical cord blood-derived mesenchymal stem cell (hUCB-MSCs) implantation on the basis of the distribution and location of medial femoral condyle (MFC) cartilage defects.

Methods: Patients who underwent hUCB-MSC implantation for MFC cartilage defects involved in isolated medial compartment osteoarthritis were included. The patients were divided into 2 groups, those with MFC defects located within the anterior-central portion (group A) and those with MFC defects extending to the posterior portion (group P).

Leveraging Vγ9Vδ2 T cells against prostate cancer through a VHH-based PSMA-Vδ2 bispecific T cell engager.

Vγ9Vδ2 T cells constitute a homogeneous effector T cell population that lyses tumors of different origin, including the prostate. We generated a bispecific T cell engager (bsTCE) to direct Vγ9Vδ2 T cells to PSMA prostate cancer (PCa) cells. The PSMA-Vδ2 bsTCE triggered healthy donor and PCa patient-derived Vγ9Vδ2 T cells to lyse PSMA PCa cell lines and patient-derived tumor cells while sparing normal prostate cells and enhanced Vγ9Vδ2 T cell antigen cross-presentation to CD8 T cells.

Tabletop Simulations in Medical Emergencies: A Scoping Review.

Tabletop simulations (TTS) are a novel educational modality used in health care education. The objective of this scoping review was to describe the use of TTS in medical emergencies, specifically settings, specialties, participants, formats, and outcomes.We included 70 studies (33 descriptive studies [47%], 33 cohort studies [47%], and 2 randomized controlled trials [3%]), of which 65 reported positive results regarding reaction and learning educational outcomes (reaction: n = 37, 53%; learning: n = 25, 36%; behavior: n = 7, 10%; result: n = 1, 1%).

CNN-Based Device-Agnostic Feature Extraction From ONH OCT Scans.

Purpose: Optical coherence tomography (OCT)-derived measurements of the optic nerve head (ONH) from different devices are not interchangeable. This poses challenges to patient follow-up and collaborative studies. Here, we present a device-agnostic method for the extraction of OCT biomarkers using artificial intelligence.

Adolescent urinary concentrations of phthalate metabolites and indices of overweight and cardiovascular risk in Dutch adolescents.

Phthalates have been linked to cardiovascular risk factors. Exposure to chemicals with endocrine disrupting properties during the pubertal period can interfere with normal endocrine processes. This study aims to determine whether adolescent urinary concentrations of phthalate metabolites are associated with indices of overweight and cardiovascular risk in 13-15-year-old children.

Assessing the Value of New Antimicrobials: Evaluations of Cefiderocol and Ceftazidime-Avibactam to Inform Delinked Payments by the NHS in England.

Objectives: The UK has recently established subscription-payment agreements for two antimicrobials: cefiderocol and ceftazidime-avibactam. This article summarises the novel value assessments that informed this process and lessons learned for future pricing and funding decisions.

Methods: The evaluations used decision modelling to predict population incremental net health effects (INHEs), informed by systematic reviews, evidence syntheses, national surveillance data and structured expert elicitation.

An examination of seizure-free outcome and visual field deficits: Anterior temporal lobectomy versus selective amygdalohippocampectomy for temporal lobe epilepsy-a systematic review and meta-analysis for comprehensive understanding.

Background: This study compares Selective Amygdalohippocampectomy (SAHE) and Anterior Temporal Lobectomy (ATL) for temporal lobe epilepsy (TLE), focusing on seizure control and visual field deficits (VFD). While previous research suggests potential benefits of SAHE, this meta-analysis aims to clarify the comparative effectiveness of bothprocedures.

Methods: This study adhered to PRISMA guidelines, comparing seizure outcomes and VFDs between SAHE and ATL for temporal lobe epilepsy.

Towards integrating imaging and immunology in glioblastoma: mapping blood immune system metrics to tumor magnetic resonance image data.

Background: Glioblastoma is the most frequent and aggressive brain cancer. It is a highly immunology-driven disease as up to a third of its mass is composed of immune cells. Apart from immunology, imaging is a major research frontier.

Gut microbiota strain richness is species specific and affects engraftment.

Despite the fundamental role of bacterial strain variation in gut microbiota function, the number of unique strains of a species that can stably colonize the human intestine is still unknown for almost all species. Here we determine the strain richness (SR) of common gut species using thousands of sequenced bacterial isolates with paired metagenomes. We show that SR varies across species, is transferable by faecal microbiota transplantation, and is uniquely low in the gut compared with soil and lake environments.

Risk of Contrast-Induced Acute Kidney Injury in Computed Tomography: A 16 Institutional Retrospective Cohort Study.

Objectives: Concern about contrast-induced acute kidney injury (CI-AKI) may delay the timely administration of contrast media for computed tomography (CT). The precise causative effect of iodinated contrast media on CI-AKI and its relevant risk factors remains an area of ongoing investigation. Therefore, this study aimed to determine the risk of CI-AKI following contrast-enhanced CT and its predisposing risk factors.

Nivolumab plus Ipilimumab in Microsatellite-Instability-High Metastatic Colorectal Cancer.

Background: Patients with microsatellite-instability-high (MSI-H) or mismatch-repair-deficient (dMMR) metastatic colorectal cancer have poor outcomes with standard chemotherapy with or without targeted therapies. Nivolumab plus ipilimumab has shown clinical benefit in nonrandomized studies of MSI-H or dMMR metastatic colorectal cancer.

Methods: In this phase 3 open-label trial, we randomly assigned patients with unresectable or metastatic colorectal cancer and MSI-H or dMMR status according to local testing to receive, in a 2:2:1 ratio, nivolumab plus ipilimumab, nivolumab alone, or chemotherapy with or without targeted therapies.

Susceptibility to and severity of SARS-CoV-2 infection according to prescription drug use-an observational study of 46,506 Danish healthcare workers.

It is not well investigated whether exposure to specific drug classes is associated with COVID-19. We investigated the risk of SARS-CoV-2 infection and severe COVID-19 among healthcare workers according to prescription drug use. We conducted an observational study among Danish healthcare workers.

Vector-Free Deep Tissue Targeting of DNA/RNA Therapeutics via Single Capacitive Discharge Conductivity-Clamped Gene Electrotransfer.

Viral vector and lipid nanoparticle based gene delivery have limitations around spatiotemporal control, transgene packaging size, and vector immune reactivity, compromising translation of nucleic acid (NA) therapeutics. In the emerging field of DNA and particularly RNA-based gene therapies, vector-free delivery platforms are identified as a key unmet need. Here, this work addresses these challenges through gene electrotransfer (GET) of "naked" polyanionic DNA/mRNA using a single needle form-factor which supports "electro-lens" based compression of the local electric field, and local control of tissue conductivity, enabling single capacitive discharge minimal charge gene delivery.

Evaluation of the Robustness Under Alkanol Stress and Adaptability of Members of the New Genus .

Many species of the genus are known to be highly tolerant to solvents and other environmental stressors. Based on phylogenomic and comparative genomic analyses, several species were recently transferred to a new genus named . Because of their unique enzymatic machinery, these strains are being discussed as novel biocatalysts in biotechnology.

Insights into the Identification of iPSC- and Monocyte-Derived Macrophage-Polarizing Compounds by AI-Fueled Cell Painting Analysis Tools.

Macrophage polarization critically contributes to a multitude of human pathologies. Hence, modulating macrophage polarization is a promising approach with enormous therapeutic potential. Macrophages are characterized by a remarkable functional and phenotypic plasticity, with pro-inflammatory (M1) and anti-inflammatory (M2) states at the extremes of a multidimensional polarization spectrum.

Galectin-1 Induces the Production of Immune-Suppressive Cytokines in Human and Mouse T Cells.

Galectin-1 is implicated in several pro-tumourigenic mechanisms and is considered immune-suppressive. The pharmacological inhibition of galectin-1 may be beneficial in cancers in which galectin-1 is overexpressed and driving cancer progression. This study aimed to further characterise the immunosuppressive cytokines influenced by galectin-1 in in vitro immune cell cultures and an in vivo inflammatory model using a recently discovered selective inhibitor of galectin-1, GB1908.

Feasibility of Non-Invasive Sentinel Lymph Node Identification in Early-Stage NSCLC Through Ultrasound Guided Intra-Tumoral Injection of Tc-Nanocolloid and Iodinated Contrast Agent During Navigation Bronchoscopy.

: As the first sentinel lymph nodes (SLN) in lung cancer are most likely to harbor metastasis, their non-invasive identification could have a significant role in future treatments. We investigated the feasibility of adding an SLN procedure to a diagnostic navigation bronchoscopy. : Thirty-one patients were included for injection of Tc-nanocolloid and an iodinated contrast agent intra-/peritumorally and assessment of tracer dissipation via SPECT and CBCT imaging.