Exploration of medicine最新文献

Cancer immunotherapies have become mainstream, targeting tumor elimination via various mechanisms, albeit with varied effectiveness. Here, we review briefly the current landscape of cancer immunotherapies and the central role of human leukocyte antigen (HLA) in them. We then propose a new kind of immunotherapy for solid tumors, where the key is the involvement of antigens and antibodies unrelated to the tumor itself. In this approach, we consider the tumor as akin to a transplanted organ, which can be rejected by two different mechanisms of incompatibility. The first involves the intra-tumor administration of mRNA blueprints of incompatible (to the patient) HLA proteins, leading to their synthesis and, hopefully, elicitation of an anti-tumor immune reaction, assuming immunocompetency. The second therapy involves the direct, intra-tumor administration of anti-A/B/H blood group antibodies lining the blood and lymph vessels of the tumor. In organ transplantation, AB incompatibility leads to organ rejection, and the same effect would be expected when anti-A/B/H antibodies (depending on the patient's ABO group) are injected into the tumor. Notably, the anti-tumor effect by the preformed anti-blood group antibodies is complement-mediated and should not be affected by tumor immunoevasion. This proposed cancer immunotherapy aimed at promoting tumor rejection via antigen incompatibility offers a novel cancer treatment approach that warrants further investigation.

Cardiovascular diseases (CVDs) are the leading causes of morbidity and mortality worldwide. Yet, drug discovery for these conditions faces significant challenges due to the complexity and heterogeneity of their underlying pathology. Recently, artificial intelligence (AI) techniques-particularly explainable AI (XAI)-have emerged as powerful multi-omics data analyzing tools to unravel pathological mechanisms and novel therapeutic targets. However, the application of XAI in cardiovascular drug discovery remains in its infancy. This review discusses the potential for the integration of AI with multi-omics data to identify novel therapeutic targets and repurpose existing drugs for myocardial infarction (MI) and heart failure (HF). This review highlights the current gap in leveraging XAI for CVDs and discusses key challenges such as data heterogeneity, model interpretability, and translational validation. This review also describes emerging approaches, including combining AI with mechanistic models, that aim to enhance the biological relevance of AI predictions. By utilizing genomic, transcriptomic, epigenomic, proteomic, and metabolomic datasets, AI-driven methods can uncover new biomarkers and predict drug responses with greater precision. The application of AI in analyzing large-scale clinical and molecular data offers significant promise in accelerating drug discovery, refining therapeutic strategies, and improving outcomes for patients with CVDs. This review highlights recent advancements, challenges, and future directions for AI-guided drug discovery in the context of MI and HF.

Vaccines are typically designed either for human or veterinary use. Using One Health principles it would be more efficient to develop a single vaccine to cover all animal and human species at threat from a specific pathogen. A major issue for designing One Health vaccines is that some commonly used human adjuvants such as aluminium salts are not suitable for some animal species, such as felines, where they can cause injection site sarcomas. Conversely, some commonly used animal adjuvants such as mineral oil emulsions are too reactogenic to be used in humans. In addition, species-specific differences in innate immune receptors such as Toll-like receptors (TLR) may mean an adjuvant that works in one species does not work in another. This review presents an overview of human and veterinary adjuvants in use and from this list identifies those that might be most suitable for use in a One Health vaccine strategy. Two notable adjuvant candidates already supported by both human and animal data are squalene oil emulsions and delta inulin-CpG combination adjuvant known as Advax-CpG55.2. These two adjuvants have already been shown to be safe and effective across multiple species including when formulated in influenza vaccines. This could be highly relevant to adjuvant selection for vaccines in development against the current North American bovine H5N1 avian influenza outbreak with the potential need to cover multiple susceptible species including birds, cattle and cats in addition to humans. Additional considerations for One Health adjuvants would be suitable administration routes and dosing across species of widely varying size, physiology and genetics. The availability of adjuvants such as squalene emulsions and Advax-CpG55.2 with broad species activity and safety, including in humans, should make One Health vaccine approaches more common in the future.

Aim: Mobile technology enables frequent, remote cognitive assessments, introducing new methodological opportunities and challenges. The study evaluated the feasibility of a high-frequency cognitive assessment schedule among older adults, in terms of total assessments and adherence to a prescribed schedule.

Methods: Thirty-three older adults were recruited from the Boston University Alzheimer's Disease Research Center (mean age = 73.5 years; 27.3% cognitively impaired; 57.6% female; 81.8% White, 18.2% Black). Participants downloaded the DANA Brain Vital mobile application on their own mobile devices during a remote study visit, and were provided a schedule with seventeen assessments to complete over one year at varying frequencies. The first segment contained three subsegments to be completed within one week, the second segment consisted of weekly subsegments spanning three weeks, and the third and fourth segments consisted of monthly subsegments spanning five and six months, respectively. Three adherence types were defined to reflect incrementally broader adherence timescales: subsegment adherence (strict adherence to each prescribed assessment period), segment adherence (completing the required number of assessments within each broader segment), and cumulative adherence (completing the total number of assessments irrespective of timing).

Results: Completion rates differed depending on the adherence timescale and corresponding adherence type. Using the strictest adherence definition (subsegment adherence), completion rates declined (from 93.9% to 72.7%, p = 0.05) during the fourth segment. However, when a broader adherence timescale was applied, completion rates did not decline. Overall completion rates increased as adherence timescale parameters were broadened from subsegment adherence (60.6%) to segment adherence (78.8%), to cumulative adherence (90.9%).

Conclusions: Older adults, including those with cognitive impairment, are able to complete remote cognitive assessments at a high-frequency, but may not necessarily adhere to prescribed schedules. Future high-frequency studies should consider adherence as a potential behavioral variable to complement cognitive test data, while recognizing the potential influence of adherence timescale on interpreting completion rates.