Disease characteristics and outcomes of acute myeloid leukemia in germline deficiency (Familial Platelet Disorder with associated Myeloid Malignancy).

Familial Platelet Disorder with associated Myeloid Malignancy (FPDMM, FPD/AML, -FPD), caused by monoallelic deleterious germline variants, is characterized by bleeding diathesis and predisposition for hematologic malignancies, particularly myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). Clinical data on FPDMM-associated AML (FPDMM-AML) are limited, complicating evidence-based clinical decision-making. Here, we present retrospective genetic and clinical data of the largest cohort of FPDMM patients reported to date.

Nasal Rehabilitation in a Patient After Basal Cell Carcinoma and Radiotherapy: A Case Report.

Nasal rehabilitation following basal cell carcinoma (BCC) and radiotherapy presents significant challenges due to the intricate balance between aesthetic and functional restoration. This case report discusses the rehabilitation of a 73-year-old male who underwent surgical excision and radiotherapy for BCC located on the left ala of the nose. Post-treatment, the patient experienced dissatisfaction with his facial appearance, negatively impacting his quality of life.

Role for the PIP-binding protein myristoylated alanine-rich C-kinase substrate in vascular tissue: A novel therapeutic target for cardiovascular disease.

In vascular smooth muscle cells (VSMCs) and vascular endothelial cells (VECs), phosphatidylinositol 4,5-bisphosphate (PIP) acts as a substrate for phospholipase C (PLC)- and phosphoinositol 3-kinase (PI3K)-mediated signaling pathways and an unmodified ligand at ion channels and other macromolecules, which are key processes in the regulation of cell physiological and pathological phenotypes. It is envisaged that these distinct roles of PIP are achieved by PIP-binding proteins, which act as PIP buffers to produce discrete pools of PIP that permits targeted release within the cell. This review discusses evidence for the expression, cell distribution, and role of myristoylated alanine-rich C-kinase substrate (MARCKS), a PIP-binding protein, in cellular signaling and function of VSMCs.

Separating triplet exciton diffusion from triplet-triplet annihilation by the introduction of a mediator.

Triplet-triplet annihilation photon upconversion (TTA-UC) combines the energy of two photons to provide one of higher energy that can be used to drive photochemical or photophysical processes. TTA-UC proceeds at high efficiencies in dilute solution, but in solid state the efficiency drastically reduces. This is because exciton diffusion, compared to molecular diffusion in solid annihilator films, suffers concentration induced quenching, undermining efficient emission.

Psilocybin and Motor Function: A Triple-Blind, Dose-Finding Study in Healthy Participants.

Background: There has been a resurgence of research into the potential therapeutic benefits of psychedelics for neuropsychiatric disorders. Classic psychedelics, such as psilocybin, exert complex effects on higher cognitive functions such as perception and awareness, but their impact on motor function remains unexplored. Moreover, there is a theoretical rationale for using psychedelics to promote motor retraining in certain neuropsychiatric conditions associated with motor dysfunction.

Explainable Artificial Intelligence in Paediatric: Challenges for the Future.

Background: Explainable artificial intelligence (XAI) emerged to improve the transparency of machine learning models and increase understanding of how models make actions and decisions. It helps to present complex models in a more digestible form from a human perspective. However, XAI is still in the development stage and must be used carefully in sensitive domains including paediatrics, where misuse might have adverse consequences.

Multidimensional Approach of Genotype and Phenotype in Stroke Etiology: The MAGPIE Study.

Background And Aims: Stroke is a leading cause of mortality and morbidity in Bangladesh. It is estimated that genetic determinants account for around 40%-60% of its etiology, similar to environmental factors. This study aimed to provide a better understanding of the genetic, environmental, and clinical risk factors in stroke patients from Bangladesh.

Reassessing the role and lifetime of Q in the energy transfer dynamics of chlorophyll .

Chlorophylls are photoactive molecular building blocks essential to most photosynthetic systems. They have comparatively simple optical spectra defined by states with near-orthogonal transition dipole moments, referred to as B and B in the blue/green spectral region, and Q and Q in the red. Underlying these spectra is a surprisingly complex electronic structure, where strong electronic-vibrational interactions are crucial to the description of state characters.

Determining the minimal important change of the recap of atopic eczema (RECAP) instrument in clinical trials.

Background: The Recap of atopic eczema (RECAP) is a patient-reported instrument designed to assess eczema control. There is a lack of evidence on the interpretability of change scores in clinical trials.

Objectives: To calculate the smallest detectable change (SDC) in RECAP and estimate the minimal important change (MIC) for RECAP using various calculation methods in three eczema clinical trial datasets.

Soluble Proteoglycans and Proteoglycan Fragments as Biomarkers of Pathological Extracellular Matrix Remodeling.

Proteoglycans and their proteolytic fragments diffuse into biological fluids such as plasma, serum, urine, or synovial fluid, where they can be detected by antibodies or mass-spectrometry. Neopeptides generated by the proteolysis of proteoglycans are recognized by specific neoepitope antibodies and can act as a proxy for the activity of certain proteases. Proteoglycan and proteoglycan fragments can be potentially used as prognostic, diagnostic, or theragnostic biomarkers for several diseases characterized by dysregulated extracellular matrix remodeling such as osteoarthritis, rheumatoid arthritis, atherosclerosis, thoracic aortic aneurysms, central nervous system disorders, viral infections, and cancer.

Treatment preferences of patients with muscle invasive bladder cancer: A discrete choice experiment.

Background: When faced with treatment options, patients are asked to participate in decision-making. We sought to determine which treatment aspects matter most for individuals treated for muscle invasive bladder cancer (MIBC), with an aim to improve understanding of patient preferences and what trade-offs patients are willing to accept. Our study consisted of a discrete choice experiment (DCE): a type of questionnaire used to elicit preferences in the absence of real-world choice.

Burden of Hyperlipidemia, Cardiovascular Mortality, and COVID-19: A Retrospective-Cohort Analysis of US Data.

Background: Hyperlipidemia is a major cardiovascular disease (CVD) risk factor, but limited data on its mortality trends in CVD over time. We assessed annual hyperlipidemia-related CVD mortality trends in the United States, including the COVID-19 pandemic's impact.

Methods And Results: Mortality data were obtained from CDC repository between 1999 and 2020 among patients ≥15 years old, using ICD-10 codes hyperlipidemia (E78.

Marital dissolution and cognition: The mediating effect of Aβ neuropathology.

Introduction: Widowhood and divorce are extremely stressful life events that are associated with dementia, but the neurobiological underpinnings of this risk remain unknown. Amyloid beta (Aβ) load may explain influences of chronic stress, commonly seen in disruptive marital transitions, on cognitive decline.

Methods: We examined whether Aβ quantified by tracer uptake on positron emission tomography mediates associations between marital dissolution and executive functioning and episodic memory performance using data from 543 cognitively normal (CN) participants from the Alzheimer's Disease Neuroimaging Initiative.

Epigenetic Diversity and the Evolutionary Potential of Wild Populations.

Fast-paced selective pressures imposed by climate change and anthropogenic activities call for adaptive evolutionary responses to emerge at ecological timescales. However, the evolution and heritability of genomic variation underlie mechanistic constraints, which dictate a slower pace of adaptation exclusively relying on standing genetic variation and novel mutations. Environmentally responsive epigenetic mechanisms can allow acclimatisation and adaptive phenotypes to arise faster than DNA sequence-based mechanisms alone.

Promise and Peril of a Genotype-First Approach to Mendelian Cardiovascular Disease.

Precision medicine, which among other aspects includes an individual's genomic data in diagnosis and management, has become the standard-of-care for Mendelian cardiovascular disease (CVD). However, early identification and management of asymptomatic patients with potentially lethal and manageable Mendelian CVD through screening, which is the promise of precision health, remains an unsolved challenge. The reduced costs of genomic sequencing have enabled the creation of biobanks containing in-depth genetic and health information, which have facilitated the understanding of genetic variation, penetrance, and expressivity, moving us closer to the genotype-first screening of asymptomatic individuals for Mendelian CVD.

Novel tumor gene expression signatures improve the overall survival prediction efficiency over tumor mutation burden and PD-L1 expression in bladder carcinoma with checkpoint blockade immunotherapy.

Although immune checkpoint blockade therapy (ICBT) has revolutionized cancer treatment with good therapeutic response in a number of human cancers, including bladder cancer, many cancers still do not respond to ICBT. Analyzing genetic signatures helps the understanding of underlying biological mechanisms. Here, based on two cohorts of bladder cancer patients receiving ICBT, we identified three novel ICBT-associated signatures in the bladder cancer microenvironment, involving genomic stability, angiogenesis and RNA regulatory, which affect PD-L1 expression and patient response to ICBT.

Apathy and effort-based decision-making in Alzheimer's disease and subjective cognitive impairment.

Introduction: Apathy is a significant feature in Alzheimer's disease (AD) and subjective cognitive impairment (SCI), though its mechanisms are not well established.

Methods: An effort-based decision-making (EBDM) framework was applied to investigate apathy in 30 AD patients, 41 SCI participants, and 55 healthy controls (HC). Data were analyzed using a drift-diffusion model (DDM) to uncover latent psychological processes.

Attentional development is altered in toddlers with congenital heart disease.

Background: Congenital Heart Disease (CHD) is the most common congenital abnormality. Survival rates are over 90%, however infants with CHD remain at high risk of attention and executive function impairments. These abilities are difficult to assess in toddlers because clinical assessments rely on language abilities which are commonly delayed in CHD.

Do Sex Ratio Distorting Microbes Inhibit the Evolution of Pesticide Resistance? An Experimental Test.

We are still largely reliant on pesticides for the suppression of arthropod pests which threaten human health and food production, but the recent rise of evolved resistance among important pest species has reduced pesticide efficacy. Despite this, our understanding of strategies that effectively limit the evolution of resistance remains weak. Male-killing sex ratio distorting microbes (SRDMs), such as and , are common among arthropod species.

Platelet-rich plasma intra-articular knee injections from open preparation techniques do not pose a higher risk of joint infection: A systematic review of 91 randomized controlled trials and 5914 injections.

Purpose: To compare the infection rate of intraarticular platelet-rich plasma (PRP) knee injections between open and closed techniques in randomized controlled trials (RCTs) published in the last decade.

Methods: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, PubMed, Scopus and Virtual Health Library were accessed in October 2022 using the terms 'platelet-rich plasma', 'PRP', 'knee' and 'tibiofemoral' alone and in combination with Boolean operators AND/OR. RCTs published during the last 10 years evaluating PRP intra-articular knee injections were considered eligible.