Myocardial Inflammation in Cardiac Transthyretin Amyloidosis: Prevalence and Potential Prognostic Implications.

Background: Despite previous histopathologic evidence for its presence, the role of myocardial inflammation in the development and progression of cardiac transthyretin amyloidosis (ATTR-CA) remains insufficiently understood. Thus, this study sought to characterize the prevalence and potential prognostic implications of myocardial inflammation in ATTR-CA.

Methods: A retrospective observational study including patients with ATTR-CA diagnosed by endomyocardial biopsy was conducted.

Dynamic map illuminates Hippo-cMyc module crosstalk driving cardiomyocyte proliferation.

Numerous regulators of cardiomyocyte (CM) proliferation have been identified, yet how they coordinate during cardiac development or regeneration is poorly understood. Here, we developed a computational model of the CM proliferation regulatory network to obtain key regulators and systems-level understanding. The model defines five modules (DNA replication, mitosis, cytokinesis, growth factor, Hippo pathway) and integrates them into a network of 72 nodes and 88 reactions that correctly predicts 73 of 78 (93.

Molecular HIV Surveillance: Beyond Cluster Detection and Response.

There has been significant controversy surrounding the use of HIV sequence data to identify outbreaks of HIV transmission since the initiation of molecular HIV surveillance (MHS) in the US. The current approach to MHS is comprehensive cluster detection and response (CDR), in which clusters of related infections are identified and used as the basis for cluster-based or population-based interventions. With CDR, there are ethical and stigma concerns around the impingement of individual privacy, as well as legal concerns around the inference of transmission in regions where HIV criminalization laws and statutes exist.

Multiomic analyses direct hypotheses for Creutzfeldt-Jakob disease risk genes.

Prions are assemblies of misfolded prion protein that cause several fatal and transmissible neurodegenerative diseases, with the most common phenotype in humans being sporadic Creutzfeldt-Jakob disease (sCJD). Aside from variation of the prion protein itself, molecular risk factors are not well understood. Prion and prion-like mechanisms are thought to underpin common neurodegenerative disorders meaning that the elucidation of mechanisms could have broad relevance.

Return to competition after ACL reconstruction: Factors influencing rates and timing in Swedish football players.

Purpose: To investigate the rate and timing for return to football league games after anterior cruciate ligament reconstruction (ACLR) in Swedish players, examining associations with sex, age, level, graft and additional ACL surgery.

Method: Data from the Swedish National Knee Registry (SNKLR) and the Swedish Football Association's IT System (FOGIS) were used. The study cohort comprised 971 football players, 64% males, who underwent primary ACLR.

Circulating Tumor DNA as a Marker of Recurrence Risk in Stage III Colorectal Cancer: The α-CORRECT Study.

Background And Objectives: Identification of colorectal cancer (CRC) patients at high risk of recurrence could be of substantial clinical use. We evaluated the association of ctDNA status, using a tumor-informed assay, with recurrence-free survival (RFS).

Methods: Stage III CRC patients were enrolled between 2016 and 2020.

Exploring the Clinical Diversity of Castleman Disease and TAFRO Syndrome: A Japanese Multicenter Study on Lymph Node Distribution Patterns.

Individuals diagnosed with Castleman disease (CD) and TAFRO syndrome (characterized by thrombocytopenia, anasarca, fever, bone marrow fibrosis, and organomegaly) displays a wide range of clinical symptoms, including varying patterns of lymph node enlargement, systemic inflammation, and impaired organ function. Some patients may present with both CD and TAFRO syndrome concurrently. A retrospective study conducted across multiple centers in Japan examined 321 cases to determine if the quantity and position of swollen lymph nodes could forecast the clinical progression and intensity of these conditions.

Clinical relevance of macromolecular complexes involving integrins, potassium and sodium ion channels and the sodium/proton antiporter in human breast cancer.

Background: Mounting evidence underline the relevance of macromolecular complexes in cancer. Integrins frequently recruit ion channels and transporters within complexes which behave as signaling hubs. A complex composed by β1 integrin, hERG1 K channel, the neonatal form of the Na channel Na 1.

Treatment with a superoxide dismutase mimetic for joint preservation during 35 and 75 days in orbit aboard the international space station, and after 120 days recovery on Earth.

Reduced weight-bearing during spaceflight has been associated with musculoskeletal degradation that risks astronaut health and performance in transit and upon reaching deep space destinations. Previous rodent experiments aboard the international space station (ISS) have identified that the spaceflight-induced molecular arthritic phenotype was characterized with an increase in oxidative stress. This study evaluated if treatment with a superoxide dismutase (SOD) mimetic on orbit could prevent spaceflight-induced damage to the knee and hip articular cartilage, and the menisci in rodents.

[Guidelines for presymptomatic genetic testing for adult-onset hereditary neuromuscular diseases in Japan].

In Japan, there are no nationwide guidelines for presymptomatic testing for hereditary neuromuscular diseases. Although each institution has been dealing with this situation by using their own procedures to date, it is necessary to develop a standardized guidelines based on the Japanese medical system, because the development of disease-modifying therapies has progressed, and we are entering an era in which early diagnosis and early treatment are necessary. The guidelines presented here were devised by the Committee on Medical Genetics of the Japan Neurological Society.

Clinical and molecular characteristics of KPC-producing Klebsiella pneumoniae bloodstream infections: results of a multicentre study.

Objectives: KPC-producing Klebsiella pneumoniae (KPC-Kp) is a great cause of concern and it is often associated with bloodstream infections (BSIs) and a high mortality rate. We identified the risk factors of KPC-Kp BSIs observed in three Italian hospitals and studied the epidemiology of KPC-Kp strains.

Methods: We performed a retrospective analysis of KPC-Kp BSIs from 2014 to 2019 in three hospitals in Central Italy (Ancona, Pesaro-Fano, and Perugia).

Neurobiology, Molecular Pathways, and Environmental Influences in Antisocial Traits and Personality Disorders.

Personality disorders (PDs) are psychiatric conditions characterized by enduring patterns of cognition, emotion, and behaviour that deviate significantly from cultural norms, causing distress or impairment. The aetiology of PDs is complex, involving both genetic and environmental factors. Genetic studies estimate the heritability of PDs at 30% to 60%, implicating genes involved in neurotransmitter regulation, such as those for serotonin transporters and dopamine receptors.

Tumor-derived extracellular vesicle PD-1 promotes tumor immune evasion via disruption of peripheral T cell homeostasis.

The programmed cell death 1 (PD-1)/PD-1 ligand 1 (PD-L1) axis mediates immune evasion of tumor, and targeting this axis has achieved some clinical benefits. The regulation of PD-1 expression in immune cells has been well studied. However, whether any other potential source of immune cell-expressed PD-1 exists remains unknown.

A novel POT1-TPD presentation: A germline pathogenic POT1 variant discovered in a patient with newly diagnosed posterior fossa ependymoma.

Introduction: POT1 tumor predisposition (POT1-TPD) is an autosomal dominant disorder characterized by increased lifetime malignancy risk. Melanoma, angiosarcoma, and chronic lymphocytic leukemia are the most frequently reported malignancies [1]. Protection of telomeres protein 1 (POT1) is part of the shelterin protein complex to maintain/protect telomeres [2].

Protocol for the generation of HLF+ HOXA+ human hematopoietic progenitor cells from pluripotent stem cells.

Hematopoietic stem cells (HSCs) generate blood and immune cells. Here, we present a protocol to differentiate human pluripotent stem cells (hPSCs) into hematopoietic progenitors that express the signature HSC transcription factors HLF, HOXA5, HOXA7, HOXA9, and HOXA10. hPSCs are dissociated, seeded, and then sequentially differentiated into posterior primitive streak, lateral mesoderm, artery endothelium, hemogenic endothelium, and hematopoietic progenitors through the sequential addition of defined, serum-free media.

Progenitor effect in the spleen drives early recovery via universal hematopoietic cell inflation.

Hematopoietic stem cells (HSCs) possess the capacity to regenerate the entire hematopoietic system. However, the precise HSC dynamics in the early post-transplantation phase remain an enigma. Clinically, the initial hematopoiesis in the post-transplantation period is critical, necessitating strategies to accelerate hematopoietic recovery.

Ethanol and the Limitations of the Osmol Gap.

Study Objective: The osmol gap can help detect and manage those with toxic alcohol exposure, and it is altered by all alcohols including ethanol. The optimal correction for ethanol that would allow accurate detection of an alternative alcohol is unclear.

Methods: We conducted a prospective cohort study to assess baseline variations in osmol gap, and then to assess the validity of 2 commonly used coefficients (correction factors) for ethanol.

Pharmacological blocking of microfibrillar-associated protein 4 reduces retinal neoangiogenesis and vascular leakage.

Neovascular age-related macular degeneration and diabetic macular edema are leading causes of vision-loss evoked by retinal neovascularization and vascular leakage. The glycoprotein microfibrillar-associated protein 4 (MFAP4) is an integrin αβ ligand present in the extracellular matrix. Single-cell transcriptomics reveal MFAP4 expression in cell-types in close proximity to vascular endothelial cells including choroidal vascular mural cells and retinal astrocytes and Müller cells.

A Comprehensive Atlas of AAV Tropism in the Mouse.

Gene therapy with Adeno-Associated Virus (AAV) vectors requires knowledge of their tropism within the body. Here we analyze the tropism of ten naturally occurring AAV serotypes (AAV3B, AAV4, AAV5, AAV6, AAV7, AAV8, AAV9, AAVrh8, AAVrh10 and AAVrh74) following systemic delivery into male and female mice. A transgene expressing ZsGreen and Cre recombinase was used to identify transduction in a cell-dependent manner based on fluorescence.

Blood-based epigenome-wide association study and prediction of alcohol consumption.

Alcohol consumption is an important risk factor for multiple diseases. It is typically assessed via self-report, which is open to measurement error through recall bias. Instead, molecular data such as blood-based DNA methylation (DNAm) could be used to derive a more objective measure of alcohol consumption by incorporating information from cytosine-phosphate-guanine (CpG) sites known to be linked to the trait.

Unveiling the omics tapestry of B-acute lymphoblastic leukemia: bridging genomics, metabolomics, and immunomics.

Acute B-lymphoblastic leukemia (B-ALL) is a highly heterogeneous hematologic malignancy, characterized by significant molecular differences among patients as the disease progresses. While the PI3K-Akt signaling pathway and metabolic reprogramming are known to play crucial roles in B-ALL, the interactions between lipid metabolism, immune pathways, and drug resistance remain unclear. In this study, we performed multi-omics analysis on different patient cohorts (newly diagnosed, relapsed, standard-risk, and poor-risk) to investigate the molecular characteristics associated with metabolism, signaling pathways, and immune regulation in B-ALL.