Association between somatic microsatellite instability, hypermutation status, and specific T cell subsets in colorectal cancer tumors.

Background: Microsatellite instability-high (MSI-high) tumors comprise ~15% of sporadic colorectal cancers (CRC) and are associated with elevated T cell infiltration. However, the universality of this response across T cell subtypes with distinct functions is unknown.

Methods: Including 1,236 CRC tumors from three observational studies, we conducted T cell profiling using a customized 9-plex (CD3, CD4, CD8, CD45RA, CD45RO, FOXP3, KRT, MKI67, and DAPI) multispectral immunofluorescence assay.

Genome sequencing reveals the impact of non-canonical exon inclusions in rare genetic disease.

Introduction: Advancements in sequencing technologies have significantly improved clinical genetic testing, yet the diagnostic yield remains around 30-40%. Emerging sequencing technologies are now being deployed in the clinical setting to address the remaining diagnostic gap.

Methods: We tested whether short-read genome sequencing could increase diagnostic yield in individuals enrolled into the UCI-GREGoR research study, who had suspected Mendelian conditions and prior inconclusive clinical genetic testing.

Designing for medication adherence in inflammatory bowel disease: multi-disciplinary approaches for self-administrable biotherapeutics.

Biotherapeutics are among the therapeutics that have revolutionized standard inflammatory bowel disease (IBD) treatment, which was previously limited to mesalamine, 5-aminosalicylic acid, corticosteroids, and classical immunosuppressants. Self-administrable biotherapeutics for IBD would enable home-based treatment and reduce the burden on medical infrastructure. Self-administration is made possible through subcutaneous injectable, oral, and rectal dosage forms.

Collective dynamical regimes predict invasion success and impacts in microbial communities.

The outcomes of ecological invasions may depend on either characteristics of the invading species or attributes of the resident community. Here we use a combination of experiments and theory to show that the interplay between dynamics, interaction strength and diversity determine the invasion outcome in microbial communities. We find that the communities with fluctuating species abundances are more invasible and diverse than stable communities, leading to a positive diversity-invasibility relationship among communities assembled in the same environment.

Artificial intelligence for hemodynamic monitoring with a wearable electrocardiogram monitor.

Background: The ability to non-invasively measure left atrial pressure would facilitate the identification of patients at risk of pulmonary congestion and guide proactive heart failure care. Wearable cardiac monitors, which record single-lead electrocardiogram data, provide information that can be leveraged to infer left atrial pressures.

Methods: We developed a deep neural network using single-lead electrocardiogram data to determine when the left atrial pressure is elevated.

Prognostic implications of system inflammation response index in atrial fibrillation patients with type 2 diabetes mellitus.

Systemic inflammation plays a crucial role in the pathogenesis and prognosis of diabetes and cardiovascular diseases. System inflammation response index (SIRI), is an emerging biomarker designed to assess the extent of systemic inflammation. We aimed to delineate the prognostic significance of SIRI in patients with both AF and type 2 diabetes mellitus (T2DM).

The galactokinase enzyme of yeast senses metabolic flux to stabilize galactose pathway regulation.

Nutrient sensors allow cells to adapt their metabolisms to match nutrient availability by regulating metabolic pathway expression. Many such sensors are cytosolic receptors that measure intracellular nutrient concentrations. One might expect that inducing the metabolic pathway that degrades a nutrient would reduce intracellular nutrient levels, destabilizing induction.

Coronary artery disease and percutaneous coronary intervention in patients with severe chronic kidney disease.

Coronary artery disease (CAD) is the leading cause of mortality among patients with chronic kidney disease (CKD), presenting unique challenges in diagnosis and management. Advanced CKD patients often present with atypical symptoms, and conventional diagnostic and interventional approaches carry risks, including contrast-induced nephropathy and the potential need for renal replacement therapy. These risks have led to the phenomenon of "renalism," where necessary procedures may be deferred due to concerns over renal injury.

Target product profile for cell-based and gene-based therapies to achieve a cure for HIV.

This target product profile (TPP) highlights the minimal and optimal characteristics for ex-vivo and in-vivo cell and gene therapy-based products aimed at achieving an HIV cure (ie, durable antiretroviral-free viral control). The need for an effective, safe, scalable, affordable, accessible, and acceptable cure for HIV infection remains a major global priority. The possibilities for cell and gene therapy-based products for an HIV cure are rapidly expanding.

Utilizing Martian samples for future planetary exploration-Characterizing hazards and resources.

One of the most surprising and important findings of the first human landings on the Moon was the discovery of a very fine layer of lunar dust covering the entire surface of Moon along with the negative impacts of this dust on the well-being and operational effectiveness of the astronauts, their equipment, and instrumentation. The United States is now planning for human missions to Mars, a planet where dust can also be expected to be ubiquitous for many or most landing sites. For these missions, the design and operations of key hardware systems must take this dust into account, especially when related to crew health and safety.

Sampling Mars: Geologic context and preliminary characterization of samples collected by the NASA Mars 2020 Perseverance Rover Mission.

The NASA Mars 2020 Perseverance Rover Mission has collected samples of rock, regolith, and atmosphere within the Noachian-aged Jezero Crater, once the site of a delta-lake system with a high potential for habitability and biosignature preservation. Between sols 109 and 1,088 of the mission, 27 sample tubes have been sealed, including witness tubes. Each sealed sample tube has been collected along with detailed documentation provided by the Perseverance instrument payload, preserving geological and environmental context.

What we can learn about Mars from the magnetism of returned samples.

The Red Planet is a magnetic planet. The Martian crust contains strong magnetization from a core dynamo that likely was active during the Noachian period when the surface may have been habitable. The evolution of the dynamo may have played a central role in the evolution of the early atmosphere and the planet's transition to the current cold and dry state.

A low pre-existing anti-NS1 humoral immunity to DENV is associated with microcephaly development after gestational ZIKV exposure.

Background: Gestational Zika virus (ZIKV) infection is associated with the development of congenital Zika syndrome (CZS), which includes microcephaly and fetal demise. The magnitude and quality of orthoflavivirus-specific humoral immunity have been previously linked to the development of CZS. However, the role of ZIKV NS1-specific humoral immunity in mothers and children with prenatal ZIKV exposure and CZS remains undefined.

Ultra-fast single-crystal CVD diamonds in the particle time-of-flight (PTOF) detector for low yield burn-history measurements on the NIF (invited).

The Particle Time of Flight (PTOF) diagnostic is a chemical vapor deposition diamond-based detector and is the only diagnostic for measuring nuclear bang times of low yield (<1013) shots on the National Ignition Facility. Recently, a comprehensive study of detector impulse responses revealed certain detectors with very fast and consistent impulse responses with a rise time of <50 ps, enabling low yield burn history measurements. At the current standoff of 50 cm, this measurement is possible with fast 14 MeV neutrons from deuterium-tritium (DT) fusion plasmas.

Good Practices for Health Technology Assessment Guideline Development: A Report of the Health Technology Assessment International, HTAsiaLink, and ISPOR Special Task Force.

Objectives: Health technology assessment (HTA) guidelines are intended to support the successful implementation of HTA by enhancing consistency and transparency in concepts, methods, processes, and use, thereby enhancing the legitimacy of the decision-making process. This report lays out good practices and practical recommendations for developing or updating HTA guidelines to ensure successful implementation.

Methods: The task force was established in 2022 and comprised experts and academics from various geographical regions, each with substantial experience in developing HTA guidelines for national health policy making.

The Relationship Between Quantitative Ischemia, Early Revascularization, and Major Adverse Cardiovascular Events: A Multicenter Study.

Background: Observational data have suggested that patients with moderate to severe ischemia benefit from revascularization. However, this was not confirmed in a large, randomized trial.

Objectives: Using a contemporary, multicenter registry, the authors evaluated differences in the association between quantitative ischemia, revascularization, and outcomes across important subgroups.

Particulate Cadmium Accumulation in the Mesopelagic Ocean.

Observations of dissolved cadmium (dCd) and phosphate (PO) suggest an unexplained loss of dCd to the particulate phase in tropical oxyclines. Here, we compile existing observations of particulate Cd and phosphorus (P), and present new data from the US GEOTRACES GP15 Pacific Meridional Transect to examine this phenomenon from a particulate Cd perspective. We use a simple algorithm to reproduce station depth profiles of particulate Cd and P via regeneration and possible subsurface accumulation.

The doctor will polygraph you now.

Artificial intelligence (AI) methods have been proposed for the prediction of social behaviors that could be reasonably understood from patient-reported information. This raises novel ethical concerns about respect, privacy, and control over patient data. Ethical concerns surrounding clinical AI systems for social behavior verification can be divided into two main categories: (1) the potential for inaccuracies/biases within such systems, and (2) the impact on trust in patient-provider relationships with the introduction of automated AI systems for "fact-checking", particularly in cases where the data/models may contradict the patient.

Neural Ordinary Differential Equations for Forecasting and Accelerating Photon Correlation Spectroscopy.

Evaluating the quantum optical properties of solid-state single-photon emitters is a time-consuming task that typically requires interferometric photon correlation experiments. Photon correlation Fourier spectroscopy (PCFS) is one such technique that measures time-resolved single-emitter line shapes and offers additional spectral information over Hong-Ou-Mandel two-photon interference but requires long experimental acquisition times. Here, we demonstrate a neural ordinary differential equation model, g2NODE, that can forecast a complete and noise-free interferometry experiment from a small subset of noisy correlation functions.

In-vitro and in-vivo assessment of biocompatibility and efficacy of ostrich eggshell membrane combined with platelet-rich plasma in Achilles tendon regeneration.

Tendon injuries present significant medical, social, and economic challenges globally. Despite advancements in tendon injury repair techniques, outcomes remain suboptimal due to inferior tissue quality and functionality. Tissue engineering offers a promising avenue for tendon regeneration, with biocompatible scaffolds playing a crucial role.

Lower ACLR Failure Rates in Bone-Soft Tissue Versus Soft Tissue-Only Allografts in Adults: A Systematic Review and Meta-analysis.

Background: While allografts are commonly used for anterior cruciate ligament reconstruction (ACLR), evidence to guide specific allograft selection is lacking.

Purpose: To compare clinical and graft failure rates after ACLR using soft tissue-only allografts and bone-soft tissue allografts in adults.

Study Design: Systematic review and meta-analysis; Level of evidence, 4.