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Acute myeloid leukemia (AML) is prevalent in both adult and pediatric patients. Despite advances in patient categorization, the heterogeneity of AML remains a challenge. Recent studies have explored the use of gene expression data to enhance AML diagnosis and prognosis, however, alternative approaches rooted in physics and chemistry may provide another level of insight into AML transformation. Utilizing publicly available databases, we analyze 884 human and mouse blood and bone marrow samples. We employ a personalized medicine strategy, combining state-transition theory and surprisal analysis, to assess the RNA transcriptome of individual patients. The transcriptome is transformed into physical parameters that represent each sample's steady state and the free energy change (FEC) from that steady state, which is the state with the lowest free energy.We found the transcriptome steady state was invariant across normal and AML samples. FEC, representing active molecular processes, varied significantly between samples and was used to create patient-specific barcodes to characterize the biology of the disease. We discovered that AML samples that were in a transition state had the highest FEC. This disease state may be characterized as the most unstable and hence the most therapeutically targetable since a change in free energy is a thermodynamic requirement for disease progression. We also found that distinct sets of ongoing processes may be at the root of otherwise similar clinical phenotypes, implying that our integrated analysis of transcriptome profiles may facilitate a personalized medicine approach to cure AML and restore a steady state in each patient.

Background: Sodium‐glucose cotransporter‐2 inhibitors (SGLT2is) are novel agents for heart failure (HF) and are now recommended in guidelines. Understanding general physicians' perspectives can help to optimise utilisation of this new medication. Aim: To understand the clinical concerns and barriers from general physicians about prescribing SGLT2is in a general medicine cohort. Methods: A questionnaire exploring clinicians' experience, comfort level and barriers to prescribing SGLT2is in patients with HF, incorporating two clinical scenarios, was disseminated to Internal Medicine Society of Australia and New Zealand members over a 2‐month period. Results: Ninety‐eight participants responded to the questionnaire (10.8% response rate). Most respondents (66.3%) were senior medical staff. Most participants worked in metropolitan settings (64.3%) and in public hospital settings (83.7%). For HF with reduced ejection fraction, 23.5% of participants reported prescribing SGLT2is frequently (defined as prescribing SGLT2is frequently over 75% of occasions). For HF with preserved ejection fraction, 57.1% of participants reported prescribing SGLT2is less than 25% of the time. Almost half of the participants (44%) expressed a high level of familiarity with therapeutic knowledge of SGLT2is, while 47% indicated high familiarity with potential side effects. Patient complexity, cost of medications and discontinuity of care were identified as important barriers. Euglycemic diabetic ketoacidosis was the side effect that caused the most hesitancy to prescribe SGLT2is in 48% of the respondents. Conclusion: General physicians in Australia and Aotearoa New Zealand are familiar with the therapeutic knowledge and side effects of SGLT2is. Patient complexity, medication cost and discontinuity of care were significant barriers to the use of SGLT2is for HF among general physicians. [ABSTRACT FROM AUTHOR]

Membrane vesicle secretion was predicted earlier as a method of elimination of proteins, lipids, and RNA from the cell. At present vesicles are thought to be a brand-new type of intercellular communication and they are playing a crucial role in numerous physiological and pathological processes. However, in this expanding field, much remains unknown regarding the origin, biogenesis, secretion, target and fate of these vesicles. Vesicle research might become a more established field as a result of a complete understanding of the isolation and analysis techniques currently in use, making it possible to utilize membrane vesicles in therapeutic settings. Thus, standardization of the isolation of vesicles is in great need. This research article deals with the isolation and characterization of two distinct bacterial species-derived membrane vesicles namely, Lactobacillus acidophilus a human gut Bacterial MVs and Pseudomonas syringae, a model phytopathogen. [ABSTRACT FROM AUTHOR]

Streptomyces is amongst the most amenable genera for biotechnological applications, and it is extensively used as a scaffold for drug development. One of the most effective therapeutic applications in the treatment of cancer is targeted therapy. Small molecule therapy is one of them, and it has gotten a lot of attention recently. Streptomyces derived compounds namely streptenols A, C, and F–I and streptazolin were subjected for ADMET property assessment. Our computational studies based on molecular docking effectively displayed the synergistic effect of streptomyces-derived compounds on the gynecological cancer target PIK3CA. These compounds were observed with the highest docking scores as well as promising intermolecular interaction stability throughout the molecular dynamic simulation. Molecular docking and molecular dynamic modeling techniques were utilized to investigate the binding mode stability of drugs using a pharmacophore scaffold, as well as physicochemical and pharmacokinetic aspects linked to alpelisib. With a root mean square fluctuation of the protein backbone of less than 0.7 nm, they demonstrated a steady binding mode in the target binding pocket. They have also prompted hydrogen bonding throughout the simulations, implying that the chemicals have firmly occupied the active site. A comprehensive study showed that streptenol D, streptenol E, streptenol C, streptenol G, streptenol F, and streptenol B can be considered as lead compounds for PIK3CA-based inhibitor design. To warrant the treatment efficacy against cancer, comprehensive computational research based on proposed chemicals must be assessed through in vitro studies. [ABSTRACT FROM AUTHOR]

Introduction: The swift uptake of new medications into clinical practice has many benefits; however, slow uptake has been seen previously with other guideline-directed medical therapies (GDMT) in heart failure (HF). Sodium glucose co-transporter 2 inhibitors are a novel therapy in HF proven to be efficacious and will have beneficial clinical outcomes if prescribed. Understanding physician perspectives on prescribing GDMT in HF can help target strategies to bridge the gap between guidelines and practice., Methods: The study followed the PRISMA guide for scoping reviews. A search was conducted using EMBASE, Medline, and PubMed databases in April 2024. Studies included were those using qualitative methods to assess physician perspectives towards prescribing any HF medication. Common themes were identified through thematic synthesis following the methods from Cochrane Training and using software MAXQDA Analysis Pro., Results: 708 studies were found in the search, with 23 full studies included. The most pertinent barriers identified were concern for medication adverse effects, unclear role responsibilities between physicians of different specialities, patient co-morbidities, and unwillingness to alter therapies of stable patients. The most identified enablers included awareness of efficacy, influence from colleagues, and the use of multi-media approaches for information dissemination. Perceptions were also found to change over time and vary among prescriber groups., Conclusions: Physicians perceive common barriers and enablers of prescribing GDMT in HF, despite differences in prescriber groups and time periods. The identified barriers and enablers may be targeted to improve implementation of GDMT into clinical practice., (© 2024 S. Karger AG, Basel.)