Evidence-based medicine (EBM) plays a crucial role in the application of large language models (LLMs) in healthcare, as it provides reliable support for medical decision-making processes. Although it benefits from current retrieval-augmented generation~(RAG) technologies, it still faces two significant challenges: the collection of dispersed evidence and the efficient organization of this evidence to support the complex queries necessary for EBM. To tackle these issues, we propose using LLMs to gather scattered evidence from multiple sources and present a knowledge hypergraph-based evidence management model to integrate these evidence while capturing intricate relationships. Furthermore, to better support complex queries, we have developed an Importance-Driven Evidence Prioritization (IDEP) algorithm that utilizes the LLM to generate multiple evidence features, each with an associated importance score, which are then used to rank the evidence and produce the final retrieval results. Experimental results from six datasets demonstrate that our approach outperforms existing RAG techniques in application domains of interest to EBM, such as medical quizzing, hallucination detection, and decision support. Testsets and the constructed knowledge graph can be accessed at \href{https://drive.google.com/file/d/1WJ9QTokK3MdkjEmwuFQxwH96j_Byawj_/view?usp=drive_link}{https://drive.google.com/rag4ebm}.
Cardiovascular diseases (CVD) are the leading global threat to human health. The clinical application of vascular stents improved the survival rates and quality of life for patients with cardiovascular diseases. However, despite the benefits stents bring to patients, there are still notable complications such as thrombosis and in-stent restenosis (ISR). Surface modification techniques represent an effective strategy to enhance the clinical efficacy of vascular stents and reduce complications. This paper reviews the development strategies of vascular stents based on surface functional coating technologies aimed at addressing the limitations in clinical application, including the inhibition of intimal hyperplasia, promotion of re-endothelialization. These strategies have improved endothelial repair and inhibited vascular remodeling, thereby promoting vascular healing post-stent implantation. However, the pathological microenvironment of target vessels and the lipid plaques are key pathological factors in the development of atherosclerosis (AS) and impaired vascular repair after percutaneous coronary intervention (PCI). Therefore, restoring normal physiological environment and removing the plaques are also treatment focuses after PCI for promoting vascular repair. Unfortunately, research in this area is limited. This paper reviews the advancements in vascular stents based on surface engineering technologies over the past decade, providing guidance for the development of stents.
Materials of engineering and construction. Mechanics of materials, Biology (General)
It has been proposed that the flat rotation curves observed at large radii in disk galaxies can be interpreted as an effect of General Relativity (GR) instead of the presence of dark matter (DM) halos in Newtonian gravity. In Ciotti (2022) the problem is rigorously explored in the special setting of the weak-field, low-velocity gravitomagnetic limit of GR. The rotation curves are obtained for purely baryonic disk models with realistic density profiles, and compared with the predictions of Newtonian gravity for the same disks, in absence of DM. The rotation curves are indistinguishable, with percentual GR corrections at all radii of the order of $\approx 10^{-6}$ or less, so that DM halos are required in gravitomagnetism as in Newtonian gravity. From a more general point of view, a list of the most urgent problems that must be addressed by any proposed GR-based alternative to the existence of DM, is given.
Since the release of ChatGPT and GPT-4, large language models (LLMs) and multimodal large language models (MLLMs) have attracted widespread attention for their exceptional capabilities in understanding, reasoning, and generation, introducing transformative paradigms for integrating artificial intelligence into medicine. This survey provides a comprehensive overview of the development, principles, application scenarios, challenges, and future directions of LLMs and MLLMs in medicine. Specifically, it begins by examining the paradigm shift, tracing the transition from traditional models to LLMs and MLLMs, and highlighting the unique advantages of these LLMs and MLLMs in medical applications. Next, the survey reviews existing medical LLMs and MLLMs, providing detailed guidance on their construction and evaluation in a clear and systematic manner. Subsequently, to underscore the substantial value of LLMs and MLLMs in healthcare, the survey explores five promising applications in the field. Finally, the survey addresses the challenges confronting medical LLMs and MLLMs and proposes practical strategies and future directions for their integration into medicine. In summary, this survey offers a comprehensive analysis of the technical methodologies and practical clinical applications of medical LLMs and MLLMs, with the goal of bridging the gap between these advanced technologies and clinical practice, thereby fostering the evolution of the next generation of intelligent healthcare systems.
Chizoba M. Enemchukwu, Christiana Nwabueze, Oluchi J. Osuala
et al.
Background: The adult human vagina hosts a complex biota containing diverse communities of microorganisms. The occurrence of multi-drug-resistant strains of these microorganisms has persistently increased due to poor hygiene and misuse or abuse of antibiotics. The vaginal microflora may exhibit patterns of growth, biochemical expression, or response to the standard drugs which consequently lead to answer the complex questions of antimicrobial resistance.
Aim: The study aimed to quantify the susceptibility profile of microorganisms isolated from vaginal discharge and evaluate the minimum inhibitory concentration of diverse antimicrobial drugs.
Methods: Fifty vaginal swabs were collected from female students of Madonna University, Nigeria while two samples were collected each from a pregnant and a non-pregnant woman at the university’s tertiary care teaching hospital. The isolates were grown in selective media and identified through Gram-staining and biochemical physiology for identification. The Kirby-Bauer disc diffusion method was used for microbial susceptibility testing, and the agar dilution method was used to determine the minimum inhibitory concentration of commonly prescribed antibiotics at the teaching hospital.
Results: Sixty-eight microorganisms comprising 17 Gram-positive (Staphylococcus sp.) and 31 Gram-negative (Escherichia coli and others) bacteria and 20 fungi (Candida sp.) were isolated. The bacteria showed a high resistance (>80%) to amoxicillin, cefuroxime, and cefixime but were relatively susceptible (35–100%) to levofloxacin and ofloxacin. Cefepime showed high activity with a minimum inhibitory concentration range of 25–50 µg/mL against the studied bacteria. The isolated fungi were susceptible to amphotericin B (35–40%) but resistant (>85%) to other antifungal drugs tested.
Conclusion: The study suggests that bacterial vaginosis prevalence at the university could best be treated with ofloxacin (second generation- fluoroquinlone), levofloxacin (third generation- fluoroquinolone), and cefepime (fourth generation- cephalosporin) due to their greater sensitivity, while candidiasis could best be treated with amphotericin B (a pyolene).
Massimo Fioranelli, Maria Grazia Roccia, Bianca Przybylek
et al.
Abstract Background The inflammatory response is fundamental to the maintenance of an organism’s physiological homeostasis. Inflammation is controlled by a series of biological events driven by specific inflammatory molecules. When inflammation is within the homeostatic range, it is considered physiological; however, it becomes pathological when it exceeds the immune system’s homeostatic control. Main text Nowadays, the treatment of chronic pathological inflammation is a challenge for pharmacology, as current anti-inflammatory drugs are intended to control acute inflammation. The aim of this narrative review was to provide an overview of the role of molecular pharmacognosy and to demonstrate how current transcriptomics techniques can make an important contribution to the study of the biological functions of natural products in the context of multicomponent/multitarget medication. From our findings, although very few studies have been identified, encouraging results for low-grade chronic inflammations (LGCIs) of various causes emerged in recent transcriptomic studies on multicomponent medicinal products composed of plant and organ extracts at the level of the skin and the musculoskeletal system (Traumeel: Tr14), the liver (Lycopodium compositum: HC-24), and the joints (Zeel-T: Ze-14). Conclusion For adequate control of LGCI, molecular pharmacognosy may be an effective approach to exploring potentially useful herbal agents that are consistent with both physiotherapeutic tradition and modern pharmacology.
Background: The dysregulation of gene expression is one of the key molecular features of colorectal cancer (CRC) development. This study aimed to investigate whether such dysregulation is reflected in rectal swab specimens of CRC patients and to evaluate its potential as a non-invasive approach for screening. Methods: We compared the expression level of 14 CRC-associated genes in tumor and adjacent non-tumor tissue of CRC patients and examined the correlation of their levels in tissue with paired rectal swab specimens. The level of these 14 genes in rectal swab specimens was compared among patients with CRC or polyp and control subjects, and the diagnostic potential of each dysregulated gene and the gene panel were evaluated. Results: The expression of <i>CXCR2</i>, <i>SAA</i>, <i>COX1</i>, <i>PPARδ</i>, <i>PPARγ</i>, <i>Groγ</i>, <i>IL8</i>, <i>p21</i>, <i>c-myc</i>, <i>CD44</i> and <i>CSF1</i> was significantly higher in CRC, and there was a significant correlation in the levels of most of them between the CRC and rectal swab specimens. In the training study, we showed that <i>CD44</i>, <i>IL8</i>, <i>CXCR2</i> and <i>c-myc</i> levels were significantly higher in the rectal swab specimens of the CRC patients. Such result was confirmed in the validation study. A panel of these four genes was developed, and ROC analysis showed that this four-gene panel could identify CRC patients with an AUC value of 0.83 and identify overall polyp and precancerous adenoma patients with AUC values of 0.6522 and 0.7322, respectively. Finally, the predictive study showed that the four-gene panel demonstrated sensitivities of 63.6%, 76.9% and 88.9% in identifying overall polyp, precancerous adenoma and CRC patients, respectively, whereas the specificity for normal subjects was 72.2%. Conclusion: The expression of CRC-associated genes in rectal swab specimens reflects the dysregulation status in colorectal tissue, and the four-gene panel is a potential non-invasive biomarker for early precancerous adenoma and CRC screening.
Background: Primary Sjögren's syndrome (pSS) stands as a chronic autoimmune disease characterized by an elusive pathogenesis. The synergy of single-cell RNA sequencing and Mendelian randomization (MR) analysis provides an opportunity to comprehensively unravel the contributory role of monocytes/macrophages in the intricate pathogenesis of pSS. Methods: Differentially expressed genes (DEGs) of various types of immune cells were analyzed after annotating single-cell RNA sequencing (scRNA-seq) data. MR analysis of expression quantitative trait loci (eQTL) and protein quantitative trait loci (pQTL) was conducted to search for key pathogenic genes and proteins. Cellular localization of pathogenic genes was performed based on scRNA-seq data. Variations in signaling pathways between immune cells were further analyzed. Results: A total of 1434 significant DEGs were identified. Among these, 60 genes exhibited strong relevance to the occurrence of pSS, of which 32 genes differentially expressed in monocytes/macrophages. CTSS was found to be a significant risk protein with a p-value of 0.001 and an odds ratio of 1.384 (1.147–1.669), showing pronounced expression in monocytes/macrophages. Furthermore, monocytes/macrophages displayed heightened expression levels of MXD1, AMPD2, TNFSF10, FTL, UBXN11, CSF3R, and LILRA5. The analysis of intercellular signaling revealed increased signal intensity in both incoming and outgoing signals in monocytes/macrophages. The signaling interactions between monocytes/macrophages, B cells, and T cells exhibited varying degrees of deviation. Conclusions: This study highlights the significant involvement of monocytes/macrophages in the pathogenesis of pSS, as evidenced by MR analysis and scRNA-seq analysis. This suggests monocytes/macrophages as a focal point for pathogenesis research and potential therapeutic targeting in pSS.
Mohammad Rasool Khazaei, Zahra Ami, Mozafar Khazaei
et al.
Background: Men’s infertility and lack of production of healthy and active sperm are concerns of recent years in mostcountries. Studies on the preparation of extracellular matrix (ECM) from decellularization of testis tissue and spermatogenesiscould provide proper results to solve some of the men’s infertility problems. This study aims to decellularize calftestis by different methods to reach a suitable scaffold and introduce it in spermatogenesis studies.Materials and Methods: In this experimental study, calf testis were decellularized by a freeze-de freeze, 1% sodiumdeoxycholate (SD), 0.1% sodium dodecyl sulfate (SDS), 0.1% SDS-vacuum, 1% SDS, 1% SDS-vacuum, and Triton-X100 methods. The content of DNA, collagen, and glycosaminoglycan (GAG) was analyzed using the kit and stainingwith Hematoxylin-Eosin, Masson’s trichrome, Alcian blue, and Orcein methods. The morphology of the scaffolds wasanalyzed with a scanning electron microscope (SEM).Results: Methods of 1% SDS, 1% SDS-vacuum, and 1% SD completely removed the cells. The preservation of collagenand GAG was confirmed using the staining kit and methods. The use of a vacuum showed greater porosity inthe SEM images. Toxicity and hemolysis were not observed in the scaffolds.Conclusion: Testis decellularization with 1% SDS and 1% SD, in addition to cell removal, could maintain the ECMstructure to a large extent without having cytotoxic and hemolysis effects.
Jesutofunmi A. Omiye, Haiwen Gui, Shawheen J. Rezaei
et al.
Large language models (LLMs) have been applied to tasks in healthcare, ranging from medical exam questions to responding to patient questions. With increasing institutional partnerships between companies producing LLMs and healthcare systems, real world clinical application is coming closer to reality. As these models gain traction, it is essential for healthcare practitioners to understand what LLMs are, their development, their current and potential applications, and the associated pitfalls when utilized in medicine. This review and accompanying tutorial aim to give an overview of these topics to aid healthcare practitioners in understanding the rapidly changing landscape of LLMs as applied to medicine.
In today's complex healthcare landscape, the pursuit of delivering optimal patient care while navigating intricate economic dynamics poses a significant challenge for healthcare service providers (HSPs). In this already complex dynamics, the emergence of clinically promising personalized medicine based treatment aims to revolutionize medicine. While personalized medicine holds tremendous potential for enhancing therapeutic outcomes, its integration within resource-constrained HSPs presents formidable challenges. In this study, we investigate the economic feasibility of implementing personalized medicine. The central objective is to strike a balance between catering to individual patient needs and making economically viable decisions. Unlike conventional binary approaches to personalized treatment, we propose a more nuanced perspective by treating personalization as a spectrum. This approach allows for greater flexibility in decision-making and resource allocation. To this end, we propose a mathematical framework to investigate our proposal, focusing on Bladder Cancer (BC) as a case study. Our results show that while it is feasible to introduce personalized medicine, a highly efficient but highly expensive one would be short-lived relative to its less effective but cheaper alternative as the latter can be provided to a larger cohort of patients, optimizing the HSP's objective better.
Direct imaging methods recover the presence, position, and shape of the unknown obstacles in time-harmonic inverse scattering without a priori knowledge of either the physical properties or the number of disconnected components of the scatterer, i.e., on the boundary condition. However, most of these methods require multi-static data and only obtain partial information about the obstacle. These qualitative methods are based on constructing indicator functions defined on the domain of interest, which help determine whether a spatial point or point source lies inside or outside the scatterer. This paper explains the main themes of each of these methods, with emphasis on highlighting the advantages and limitations of each scheme. Additionally, we will classify each method and describe how some of these methods are closely related to each other.
Large language models (LLMs), such as ChatGPT, have received substantial attention due to their capabilities for understanding and generating human language. While there has been a burgeoning trend in research focusing on the employment of LLMs in supporting different medical tasks (e.g., enhancing clinical diagnostics and providing medical education), a review of these efforts, particularly their development, practical applications, and outcomes in medicine, remains scarce. Therefore, this review aims to provide a detailed overview of the development and deployment of LLMs in medicine, including the challenges and opportunities they face. In terms of development, we provide a detailed introduction to the principles of existing medical LLMs, including their basic model structures, number of parameters, and sources and scales of data used for model development. It serves as a guide for practitioners in developing medical LLMs tailored to their specific needs. In terms of deployment, we offer a comparison of the performance of different LLMs across various medical tasks, and further compare them with state-of-the-art lightweight models, aiming to provide an understanding of the advantages and limitations of LLMs in medicine. Overall, in this review, we address the following questions: 1) What are the practices for developing medical LLMs 2) How to measure the medical task performance of LLMs in a medical setting? 3) How have medical LLMs been employed in real-world practice? 4) What challenges arise from the use of medical LLMs? and 5) How to more effectively develop and deploy medical LLMs? By answering these questions, this review aims to provide insights into the opportunities for LLMs in medicine and serve as a practical resource. We also maintain a regularly updated list of practical guides on medical LLMs at https://github.com/AI-in-Health/MedLLMsPracticalGuide
František Bartoš, Maximilian Maier, Eric-Jan Wagenmakers
et al.
Publication selection bias undermines the systematic accumulation of evidence. To assess the extent of this problem, we survey over 68,000 meta-analyses containing over 700,000 effect size estimates from medicine (67,386/597,699), environmental sciences (199/12,707), psychology (605/23,563), and economics (327/91,421). Our results indicate that meta-analyses in economics are the most severely contaminated by publication selection bias, closely followed by meta-analyses in environmental sciences and psychology, whereas meta-analyses in medicine are contaminated the least. After adjusting for publication selection bias, the median probability of the presence of an effect decreased from 99.9% to 29.7% in economics, from 98.9% to 55.7% in psychology, from 99.8% to 70.7% in environmental sciences, and from 38.0% to 29.7% in medicine. The median absolute effect sizes (in terms of standardized mean differences) decreased from d = 0.20 to d = 0.07 in economics, from d = 0.37 to d = 0.26 in psychology, from d = 0.62 to d = 0.43 in environmental sciences, and from d = 0.24 to d = 0.13 in medicine.
Mahdie Kian, Elham Hosseini, Tooba Abdizadeh
et al.
Polycystic ovary syndrome (PCOS) is the most common cause of women’s infertility. Some inflammatory pathways play a pivotal role in the pathogenesis of PCOS. This study aimed to investigate the possible beneficial effects of minocycline on chemokine-like receptor 1 (CMKLR1) and Insulin Receptor (INSR) in a PCOS model. A molecular docking study was implemented using Molecular Operating Environment (MOE) software. The PCOS was induced in NMRI mice (mean body weight 14.47±0.23) by 28 days estradiol valerate injection (2 mg/kg/day). The mice were then divided into six groups (n=8 per group, mean body weight 17.77± 0.26): control (received normal saline), PCOS model, control for minocycline, minocycline treated PCOS (50 mg/kg), letrozole treated PCOS (0.5 mg/kg), and metformin-treated PCOS (300 mg/kg). Serum FSH, LH, estradiol (E2), and testosterone were detected by ELISA. The ovarian tissues were stained by hematoxylin and eosin. The CMKLR1 and INSR expression levels were determined by Real-time-PCR. The molecular docking studies showed scores of -10.92 and -9.30 kcal/mol, respectively, for minocycline with CMKLR1 and INSR. Estradiol valerate treatment led to a significant increase in E2, graffian follicle, and decrease in corpus luteum (CL) numbers (P<0.05), while minocycline treatment improved these PCOS features. The minocycline treatment significantly decreased the CMKLR1 expression and increased the INSR expression (P<0.05) while the CMKLR1 expression was increased in PCOS model. Minocycline may improve ovulation in PCOS model by returning E2 to a normal level and increasing CL number (ovulation signs). These beneficial outcomes may be related to the changes in CMKLR1 and INSR gene expression involved in glucose metabolism and inflammation.
Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Biology (General)
TO THE EDITOR: Doherty (1) neglects to mention that many luxury care clinics are sponsored by academic medical centers. Some partner with national concierge care companies. Marketing for such clinics is directed at the heads of successful small and large companies, who are disproportionately white men. Many physicians who staff luxury care clinics limit their practices to the wealthy (2, 3). Physicians in retainer practices care for fewer African Americans, Hispanics, and Medicaid patients than those in other types of practices; moreover, physicians who switch to a retainer practice keep an average of only 12% of their former patients, thus burdening other, already overworked physicians in the community (4). The general public contributes substantially to the education and training of new physicians through state and federal taxes and thus might find it hard to accept physicians limiting their practices to wealthy persons (5). Although academic medical centers, traditional providers for the poor and underserved, might justify sponsoring luxury clinics via a utilitarian argument, only 2 programs use income from these ventures to cross-subsidize care for indigent persons or teaching programs. There is no high-quality evidence documenting a higher caliber of care in concierge practices, and few data support the clinical or cost-effectiveness of many of the unnecessary tests offered to asymptomatic clients (2, 3). Overtesting may result in false-positive results, leading to further unnecessary investigations, additional costs, and heightened anxiety. True-positive results may lead to overdiagnosis of conditions that would not have become clinically significant, leading to further risky interventions and possibly impairing future insurability. The use of clinically unjustifiable tests erodes the scientific underpinnings of medical practice, runs counter to the ethical obligations of physicians to responsibly manage limited health care resources, and likely leads to worse care. Most training in professional ethics, as well as the development and teaching of evidence-based practice guidelines, takes place in medical schools and teaching hospitals. No data are available on the participation of medical students and residents in luxury care clinics at teaching hospitals. For such institutions to teach students to treat all patients equally, combat inequalities in health care access and outcomes, and practice evidence-based medicine while at the same time supporting clinics that do the antithesis is troubling. At the least, trainees should not be allowed to work in such clinics.