Fine-tuning Large Language Model (LLM) Artificial Intelligence Chatbots in Ophthalmology and LLM-based evaluation using GPT-4

Purpose: To assess the alignment of GPT-4-based evaluation to human clinician experts, for the evaluation of responses to ophthalmology-related patient queries generated by fine-tuned LLM chatbots. Methods: 400 ophthalmology questions and paired answers were created by ophthalmologists to represent commonly asked patient questions, divided into fine-tuning (368; 92%), and testing (40; 8%). We find-tuned 5 different LLMs, including LLAMA2-7b, LLAMA2-7b-Chat, LLAMA2-13b, and LLAMA2-13b-Chat. For the testing dataset, additional 8 glaucoma QnA pairs were included. 200 responses to the testing dataset were generated by 5 fine-tuned LLMs for evaluation. A customized clinical evaluation rubric was used to guide GPT-4 evaluation, grounded on clinical accuracy, relevance, patient safety, and ease of understanding. GPT-4 evaluation was then compared against ranking by 5 clinicians for clinical alignment. Results: Among all fine-tuned LLMs, GPT-3.5 scored the highest (87.1%), followed by LLAMA2-13b (80.9%), LLAMA2-13b-chat (75.5%), LLAMA2-7b-Chat (70%) and LLAMA2-7b (68.8%) based on the GPT-4 evaluation. GPT-4 evaluation demonstrated significant agreement with human clinician rankings, with Spearman and Kendall Tau correlation coefficients of 0.90 and 0.80 respectively; while correlation based on Cohen Kappa was more modest at 0.50. Notably, qualitative analysis and the glaucoma sub-analysis revealed clinical inaccuracies in the LLM-generated responses, which were appropriately identified by the GPT-4 evaluation. Conclusion: The notable clinical alignment of GPT-4 evaluation highlighted its potential to streamline the clinical evaluation of LLM chatbot responses to healthcare-related queries. By complementing the existing clinician-dependent manual grading, this efficient and automated evaluation could assist the validation of future developments in LLM applications for healthcare.Comment: 13 Pages, 1 Figure, 8 Table

In vitro antibacterial activity of crude medicinal plant extracts against ampicillin+penicillin-resistant Staphylococcus aureus

Staphylococcus aureus is the leading cause for foodborne diseases. Extensive use of antibiotics has led to emergence of antibiotic-resistant S. aureus. Hence, interest on natural plant-based alternative which limits the use of synthetic chemicals is growing. The present work evaluated the antibacterial capacity of garlic, aloe vera, galangal, pineapple peel, neem, papaya leaf, lemongrass, peppermint, nutmeg and clove separately extracted with hexane, ethanol and water to a final concentration of 10% w/v against ampicillin+penicillin-resistant isolates of S. aureus in vitro. Streptomycin was used as a drug control against the resistant isolates; BRS023, BRS068 and DRS072. According to the interpretive standards for inhibition zone diameter provided by the Clinical and Laboratory Standards Institute, isolates BRS068 and DRS072 were considered resistant (≤ 12 mm), and isolate BRS023 was considered intermediate (13-14 mm). Against these isolates, all crude plant extracts exhibited varying degrees of inhibition. However, a coherent trend was observed in the inhibition between resistant and intermediate isolates regardless of plants and solvents used. It was also found that extraction solvent types impacted the resulting antibacterial activity. In terms of positive inhibition, the solvents were ranked in the order of hexane (77%) > water (73%) > ethanol (57%). 10% hexane extract of galangal gave the overall highest inhibition zones (17.8 ± 1.4 mm) closely followed by 10% ethanol extract of nutmeg (16.3 ± 1.1 mm). Further phytochemical analyses of the antibacterial compounds from galangal and nutmeg, and their minimum inhibitory concentration (MIC) are needed. Potential applications of plant-based antibacterial compounds as natural, costeffective and less-toxic food preservatives against drug-resistant foodborne pathogens should be explored

Alterations of Renal Epithelial Glucose and Uric Acid Transporters in Fructose Induced Metabolic Syndrome

Background/Aims: Hyperglycemia and hyperuricemia are two major disorders of Metabolic syndrome. Kidney plays a crucial role in maintaining the homeostasis of uric acid and glucose. The aim of the study was to examine the changes of renal glucose and uric acid transporters in animals with metabolic syndrome. Methods: Sprague-Dawley rats were fed with high fructose diet (60%) for 3 months (FR-3) and 5 months (FR-5). At the end study, serum and urine biochemical data were compared. Gene expression and protein abundance of renal GLUT1, GLUT2, GLUT9, SGLT1, SGLT2, UAT and URAT1 was investigated by using RT-PCR and immunohistochemical staining. Results: Metabolic syndrome was induced by high-fructose diet. Systolic blood pressure and proteinuria was significantly increased in FR-5 animals. In kidney tissue, gene expression of GLUT2 and SGLT2 increased significantly in a time dependent manner. GLUT9, SGLT1 and UAT were also significantly upregulated in FR-5. Immunohistochemical study showed a significant increase of SGLT1 in both FR-3 (413.5 ± 88.3% of control, p< 0.001) and FR-5 (677.6 ± 26.5% of control, p< 0.001). Also, SGLT2 protein was increased in both FR-3 (643.1 ± 41.3% of control, p< 0.001) and FR-5 (563.3 ± 21.7% of control, p< 0.001). Fructose rich food also induced increase of UAT by nearly 5-fold in both FR-3 and FR-5 (both p< 0.05) and more than 3-fold of GLUT-9 in FR-3 and FR-5 (both p< 0.05). Conclusion: Long term high fructose diet induced metabolic syndrome with increased blood pressure and proteinuria in rats. Metabolic syndrome was associated with dual increase in renal glucose and uric acid transporters, including SGLT1, SGLT2, GLUT2, GLUT9 and UAT

Mechanism of Evolution Shared by Gene and Language

We propose a general mechanism for evolution to explain the diversity of gene and language. To quantify their common features and reveal the hidden structures, several statistical properties and patterns are examined based on a new method called the rank-rank analysis. We find that the classical correspondence, "domain plays the role of word in gene language", is not rigorous, and propose to replace domain by protein. In addition, we devise a new evolution unit, syllgram, to include the characteristics of spoken and written language. Based on the correspondence between (protein, domain) and (word, syllgram), we discover that both gene and language shared a common scaling structure and scale-free network. Like the Rosetta stone, this work may help decipher the secret behind non-coding DNA and unknown languages.Comment: 15 pages, 13 figures, 3 tabl

Replication and Meta-analysis of the Association between BDNF Val66Met Polymorphism and Cognitive Impairment in Patients Receiving Chemotherapy.

Cancer-related cognitive impairment (CRCI) adversely affects cancer patients. We had previously demonstrated that the BDNF Val66Met genetic polymorphism is associated with lower odds of subjective CRCI in the multitasking and verbal ability domains among breast cancer patients receiving chemotherapy. To further assess our previous findings, we evaluated the association of BDNF Val66Met polymorphism with subjective and objective CRCI in a temporally separate cohort of patients and pooled findings from both the original (n = 145) and current (n = 193) cohorts in a meta-analysis. Subjective CRCI was assessed using FACT-Cog. Objective CRCI was evaluated using computerized neuropsychological tests. Genotyping was carried out using Sanger sequencing. The association of BDNF Val66Met genotypes and CRCI was examined with logistic regression. A fixed-effect meta-analysis was conducted using the inverse variance method. In the meta-analysis (n = 338), significantly lower odds of CRCI were associated with Met allele carriers based on the global FACT-Cog score (OR = 0.52, 95% CI 0.29-0.94). Furthermore, Met allele carriers were at lower odds of developing impairment in the domains of memory (OR = 0.34, 95% CI: 0.17-0.70), multitasking (OR = 0.33, 95% CI: 0.18-0.59), and verbal ability (OR = 0.46, 95% CI: 0.24-0.88). Consistent with the previous study, lower odds of subjective CRCI among patients with the BDNF Met allele was observed after adjusting for potential confounders in the multitasking (OR = 0.30, 95% CI: 0.14-0.67) domain. In conclusion, carriers of the BDNF Met allele were protected against global subjective CRCI, particularly in the domains of memory, multitasking, and verbal ability. Our findings further contribute to the understanding of CRCI pathophysiology

Combined novice, near-peer, e-mentoring palliative medicine program: A mixed method study in Singapore

INTRODUCTION:An acute shortage of senior mentors saw the Palliative Medicine Initiative (PMI) combine its novice mentoring program with electronic and peer mentoring to overcome insufficient mentoring support of medical students and junior doctors by senior clinicians. A three-phased evaluation was carried out to evaluate mentees' experiences within the new CNEP mentoring program. METHODS:Phase 1 saw use of a Delphi process to create a content-valid questionnaire from data drawn from 9 systematic reviews of key aspects of novice mentoring. In Phase 2 Cognitive Interviews were used to evaluate the tool. The tool was then piloted amongst mentees in the CNEP program. Phase 3 compared mentee's experiences in the CNEP program with those from the PMI's novice mentoring program. RESULTS:Thematic analysis of open-ended responses revealed three themes-the CNEP mentoring process, its benefits and challenges that expound on the descriptive statistical analysis of specific close-ended and Likert scale responses of the survey. The results show mentee experiences in the PMI's novice mentoring program and the CNEP program to be similar and that the addition of near peer and e-mentoring processes enhance communications and support of mentees. CONCLUSION:CNEP mentoring is an evolved form of novice mentoring built on a consistent mentoring approach supported by an effective host organization. The host organization marshals assessment, support and oversight of the program and allows flexibility within the approach to meet the particular needs of mentees, mentors and senior mentors. Whilst near-peer mentors and e-mentoring can make up for the lack of senior mentor availability, their effectiveness hinges upon a common mentoring approach. To better support the CNEP program deeper understanding of the mentoring dynamics, policing and mentor and mentee training processes are required. The CNEP mentoring tool too needs to be validated

Potential medicinal herb for cardiovascular health : a comprehensive review on Salviae miltiorrhizae

Cardiovascular disease (CVD) and its associated risk factors have been ranked the number 1 cause of mortality in noncommunicable diseases worldwide and Malaysia. The high statistic in CVD mortality indicates gaps and limitations in current treatment strategies using long-term drug prescription therapies. Hence, an immediate quest for alternative and effective treatments is needed. Medicinal herbs, which are ethnopharmacologically used to treat a wide range of conditions, have been used as an alternative or supplementary treatment for CVDs and their associated risk factors. The roots of Salviae miltiorrhizae have been traditionally used for centuries to treat various diseases including neurological disorders, cancer, and even coronary heart disease. Increasing evidence demonstrated a pharmacological basis for the action of S. miltiorrhizae and its active compounds, suggesting its potential in treating CVD. The objectives of this review were first to summarize published literature and synthesize the new body of knowledge on the use of S. miltiorrhizae as the potential medicinal herb that will positively impact the cardiovascular system, and secondly to elucidate the underlying mechanisms involved in promoting cardiovascular health. It is hoped that identification of key regulatory pathways by lipophilic and hydrophilic active compounds from S. miltiorrhizae will aid further investigation of its safety and efficacy to promote the use of evidence-based traditional medicinal herbs in alleviating symptoms and improve the prognosis of CVDs and their associated risk factors

Gut Microbiome of a Multiethnic Community Possessed No Predominant Microbiota

With increasing globalisation, various diets from around the world are readily available in global cities. This study aimed to verify if multiethnic dietary habits destabilised the gut microbiome in response to frequent changes, leading to readily colonisation of exogenous microbes. This may have health implications. We profiled Singapore young adults of different ethnicities for dietary habits, faecal type, gut microbiome and cytokine levels. Subjects were challenged with Lactobacillus casei, and corresponding changes in microbiome and cytokines were evaluated. Here, we found that the majority of young adults had normal stool types (73% Bristol Scale Types 3 and 4) and faecal microbiome categorised into three clusters, irrespective of race and gender. Cluster 1 was dominated by Bacteroides, Cluster 2 by Prevotella, while Cluster 3 showed a marginal increase in Blautia, Ruminococaceae and Ruminococcus, without a predominant microbiota. These youngsters in the three faecal microbiome clusters preferred Western high sugary beverages, Southeast Asian plant-rich diet and Asian/Western diets in rotation, respectively. Multiethnic dietary habits (Cluster 3) led to a gut microbiome without predominant microbiota yet demonstrated colonisation resistance to Lactobacillus. Although Bacteroides and Prevotella are reported to be health-promoting but also risk factors for some illnesses, Singapore-style dietary rotation habits may alleviate Bacteroides and Prevotella associated ill effects. Different immunological outcome was observed during consumption of the lactobacilli among the three microbiome clusters.</p