We aimed to examine the adherence of large language models (LLMs) to bacterial meningitis guidelines using a hypothetical medical case, highlighting their utility and limitations in healthcare.
A simulated clinical scenario of a patient with bacterial meningitis secondary to mastoiditis was presented in three independent sessions to seven publicly accessible LLMs (Bard, Bing, Claude-2, GTP-3.5, GTP-4, Llama, PaLM). Responses were evaluated for adherence to good clinical practice and two international meningitis guidelines.
A central nervous system infection was identified in 90% of LLM sessions. All recommended imaging, while 81% suggested lumbar puncture. Blood cultures and specific mastoiditis work-up were proposed in only 62% and 38% sessions, respectively. Only 38% of sessions provided the correct empirical antibiotic treatment, while antiviral treatment and dexamethasone were advised in 33% and 24%, respectively. Misleading statements were generated in 52%. No significant correlation was found between LLMs\' text length and performance (r=0.29, p=0.20). Among all LLMs, GTP-4 demonstrated the best performance.
Latest LLMs provide valuable advice on differential diagnosis and diagnostic procedures but significantly vary in treatment-specific information for bacterial meningitis when introduced to a realistic clinical scenario. Misleading statements were common, with performance differences attributed to each LLM\'s unique algorithm rather than output length.
Users must be aware of such limitations and performance variability when considering LLMs as a support tool for medical decision-making. Further research is needed to refine these models\' comprehension of complex medical scenarios and their ability to provide reliable information.

BACKGROUND: Elevated γ-glutamyl transferase (γ-GTP) levels are associated with metabolic syndrome. We investigated the association of cumulative exposure to high γ-GTP with the risk of cardiovascular disease (CVD) in a large-scale population.
METHODS: Using nationally representative data from the Korean National Health Insurance system, 1,640,127 people with 4 years of consecutive γ-GTP measurements from 2009 to 2012 were included and followed up until the end of 2019. For each year of the study period, participants were grouped by the number of exposures to the highest γ-GTP quartile (0-4), and the sum of quartiles (0-12) was defined as cumulative γ-GTP exposure. The hazard ratio for CVD was evaluated using the Cox proportional hazards model.
RESULTS: During the 6.4 years of follow-up, there were 15,980 cases (0.97%) of myocardial infarction (MI), 14,563 (0.89%) of stroke, 29,717 (1.81%) of CVD, and 25,916 (1.58%) of death. Persistent exposure to high γ-GTP levels was associated with higher risks of MI, stroke, CVD, and death than those without such exposure. The risks of MI, stroke, CVD, and mortality increased in a dose-dependent manner according to total cumulative γ-GTP (all P for trend <0.0001). Subjects younger than 65 years, with a body mass index <25 kg/m2, and without hypertension or fatty liver showed a stronger relationship between cumulative γ-GTP and the incidence of MI, CVD, and death.
CONCLUSIONS: Cumulative γ-GTP elevation is associated with CVD. γ-GTP could be more widely used as an early marker of CVD risk, especially in individuals without traditional CVD risk factors.

The Gutong Patch (GTP) is common in clinical practice for bone diseases. This study compared the efficacy and safety of GTP and nonsteroidal anti-inflammatory drugs (NSAIDs) for KOA patients from 35 medical centers assigned to GTP, selective COX-2 inhibitor (SCI), GTP + SCI, non-selective COX-2 inhibitor (NSCI), and GTP + NSCI groups. The visual analog scale (VAS) pain score, EuroQol-VAS, EuroQol 5D-3 L, time to articular pain relief / disappearance, and joint motion recovery were the efficacy assessments. Safety assessments included contact dermatitis, gastrointestinal disorders, etc. The p-value < 0.05 was considered statistically significant. After statistical analysis, the SCI and GTP + SCI groups showed better improvement of VAS than the GTP group; the time to articular pain relief in the NSCI group was shorter than that in GTP and SCI group; the time to joint motion recovery in the GTP + NSCI group was longer than that in the SCI group. Additionally, the improvement of the quality of life in all groups was significant after treatments. While the incidence of gastrointestinal adverse events in the NSAIDs group was higher than that in the GTP and GTP + NSAIDs groups. GTP and NSAIDs are effective for KOA patients, and GTP is more suitable for KOA patients with cardiovascular and gastrointestinal comorbidities. This study was approved by the Ethics Committee at Peking Union Medical College Hospital (HS-1766) and registered in the Chinese Clinical Trial Registry (ChiCTR2100046391).

Sotorasib (LUMAKRAS®) is the first RAS inhibitor that selectively binds to KRAS G12C and irreversibly inhibits the conformational change from the inactive to active form of KRAS. The gene mutation that produces KRAS G12C protein, which is the target of sotorasib, is one of the oncogenic drivers observed in non-small cell lung cancer (NSCLC), and the KRAS G12C mutation causes conformational changes to maintain KRAS in an active form enhancing downstream signals, leading to tumor cell proliferation and survival. Although the role of KRAS in human cancers has been known for decades, role of RAS in normal cells, the high affinity between RAS and GTP, high concentration of intracellular GTP, and the smooth surface of RAS protein makes it difficult to develop drugs targeting RAS mutation for a long time. However, the discovery of the Switch II pocket of KRAS in 2013 and the report of compounds that specifically bind to KRAS G12C led to the development of sotorasib. Sotorasib inhibited the growth of KRAS G12C positive cell lines and suppressed tumor growth in a mouse model implanted with the KRAS G12C positive cell line. In clinical trials, objective responses were seen in 37.4% of patients with KRAS G12C positive advanced NSCLC taking 960mg sotorasib orally per day. There were no dose-limiting toxicities and other adverse events were tolerable. Sotorasib was designated as an orphan drug in March 2021 and approved in January 2022 for KRAS G12C positive unresectable/recurrent NSCLC that has progressed after 1st line therapy in Japan.

We aimed to determine whether serum uric acid (SUA) and body mass index (BMI) trajectories in childhood have longitudinal association with liver enzymes in adolescence.
We conducted a study using data from the Ewha Birth and Growth Cohort. Individual trajectories of SUA (n = 203) and BMI (n = 206) from 5, 7, and 9 years were defined by group-based trajectory modeling. Also, liver function enzymes were collected at 11 to 12 year of age (Aspartate Aminotransferase [AST], Alanine transaminase [ALT], and Gamma-glutamyl transferase [γ-GTP]) (n = 206). Using a generalized linear model, the effects of SUA trajectory and BMI trajectory on liver function enzymes were assessed. We also assessed the interaction effect of SUA and BMI trajectories on liver enzymes.
For trajectory patterns, both SUA and BMI were classified into two distinct groups (High or Low). Both trajectory of SUA and BMI in childhood were positively associated with levels of liver enzymes at 11-12 years of age. The results showed that the combined effect of SUA and BMI trajectories on liver enzymes had a higher means in high-risk group (high SUA-high BMI trajectories group) than in low-risk group (low SUA-low BMI trajectories group) for ALT and γ-GTP, respectively. It remained significant association when adjusted for covariates. In addition, the interaction of BMI and SUA trajectories showed a significant synergistic effect.
Elevated childhood SUA and BMI trajectories are associated with increased liver enzymes in beginning of adolescent. This finding suggesting that early interventions in SUA and BMI may need for optimization of liver enzymes as potential marker for development of related disease in later life.

Aim: This study aims to build the capacity of the people at grass root level as gatekeepers of mental health. It will assess the effectiveness of the Gatekeeper Training Program (GTP) on gatekeeper behaviour, awareness, attitude, and mental help seeking intention. Design: An evaluative research approach in two phases. Phase 1: Cross-sectional house-to-house exploratory survey. Phase 2: A quasi-experimental design with multiple follow ups at 0, 6 and 12 months. Method: Data will be collected using standardized tools like Mental Health Knowledge Questionnaire (MHKQ), Community Attitude towards Mentally Ill (CAMIS), Mental Help Seeking Intention (MHSIS) and Gatekeeper Behavior Scale (GBS). For Phase 1, a house-to-house survey will be conducted among the selected colonies of Koraga tribe to determine their awareness, attitude, and mental help seeking intention regarding common mental health problems. Phase 2 includes identification of the leaders/representatives of the selected tribal colonies, and involving them in GTP. Pre-test and multiple post-test will be conducted in Phase 2 at 0, 6, 12 months.  The study is funded by Indian Council of Medical Research from 16 August 2021 for 3 years duration. Discussion: Treatment gap in psychiatric disorders remains an issue of great concern. Evidence based research promotes task shifting approaches in dealing with mental health problems in the community. Capacity building programs like GTP for the underprivileged section of the society are important especially in low and middle income group of countries. Impact: This need based GTP, will ensure mental health first aid in the society. Early identification of people with mental health problems at their doorsteps has huge impact on the prognosis of the illness, closing the treatment gap and stigma reduction.

Phthalate exposure is ubiquitous due to the widespread use of plastic products in daily life, and affects several health outcomes, including metabolic diseases. In this study, we evaluated the effects of phthalate exposure in childhood on liver function in adolescence.  METHODS: Among 164 Ewha Birth and Growth Cohort Study participants followed up during two exposure periods (when the children were aged 3-5 and 7-9 years), 126 were followed up at age 10-15 years. To investigate the relationship between phthalate exposure during the two periods and liver enzyme levels (ALT, AST, γ-GTP) in adolescence, differences between groups and the dose-response relationship were analyzed. In addition, we investigated differences in liver enzymes between groups based on the combined exposure levels (high or low) during the two periods. The interaction effect between phthalates and BMI on liver enzyme levels was evaluated, stratified by sex.  RESULTS: In the 3-5 year-old exposure period, ALT levels tended to increase as MECPP levels increased, while γ-GTP levels tended to increase as MiBP, MnBP, and ∑DBP levels increased. In addition, the group exposed to consistently high levels of phthalates at both time points had higher liver enzyme levels compared to the group that had lower exposure. In particular, the interaction effect between some phthalate metabolites and BMI in 3-5 year olds affected AST and γ-GTP levels in adolescence only in girls.
Exposure to phthalates in daily life during childhood affects liver enzyme levels in adolescence. Elevated liver enzyme levels are associated with the development of metabolic syndrome, implying that attention should be paid to phthalate exposure during childhood.

EngA, a GTPase contains two GTP binding domains [GD1, GD2], and the C-terminal KH domain shown to be involved in the later stages of ribosome maturation. Association of EngA to the ribosomal subunit in the intermediate stage of maturation is essential for complete ribosome maturation. However, this association was shown to be dependent on the nucleotide bound combinations. This nucleotide dependent association tendency is attributed to the conformational changes that occur among different nucleotide bound combinations. Therefore, to explore the conformational changes, all-atom molecular dynamics simulations for Bacillus subtilis EngA in different nucleotide bound combinations along with the presence or absence of Mg2+ in the active-sites were carried out. The presence of Mg2+ along with the bound nucleotide at the GD2 active-site dictates the GD2-Sw-II mobility, but the GD1-Sw-II mobility has not shown any nucleotide or Mg2+ dependent movement. However, the GD1-Sw-II secondary conformations are shown to be influenced by the GD2 nucleotide bound state. This allosteric connection between the GD2 active-site and the GD1-Sw-II is also observed through the dynamic network analysis. Further, the exploration of the GD1-KH interface interactions exhibited a more attractive tendency when GD1 is bound to GTP-Mg2+. In addition, the presence of Mg2+ stabilizes active-site water and also increases the distances between the α- and γ- phosphates of the bound GTP. Curiously, three water molecules in the GD1 active-site and only one water molecule in the GD2 active-site are stabilized. This indicates that the probability of GTP hydrolysis is more in GD1 compared to GD2.Communicated by Ramaswamy H. Sarma.

FtsZ filaments are the major structural component of the bacterial Z ring and are drivers of bacterial division. Crystal structures for FtsZ from some Gram-positive bacteria in the presence of GTP analogs suggest the possibility of a high-energy, \"tense\" conformation. It remains important to elucidate whether this tense form is the dominant form in filaments. Using dynamic nuclear polarization (DNP) solid-state nuclear magnetic resonance (NMR) and differential isotopic labeling, we directly detected residues located at the intermonomer interface of GTP-bound wild-type (WT) Escherichia coli FtsZ filaments. We combined chemical shift prediction, homology modeling, and heteronuclear dipolar recoupling techniques to characterize the E. coli FtsZ filament interface and demonstrated that the monomers in active filaments assume a tense conformation. IMPORTANCE Bacterial replication is dependent on the cytoskeletal protein FtsZ, which forms filaments that scaffold and recruit other essential division proteins. While the FtsZ monomer is well studied across organisms, many questions remain about how the filaments form and function. Recently, a second monomer form was identified in Staphylococcus aureus that has far-reaching implications for FtsZ structure and function. However, to date, this form has not been directly observed outside S. aureus. In this study, we used solid-state NMR and dynamic nuclear polarization (DNP) to directly study the filaments of E. coli FtsZ to demonstrate that E. coli FtsZ filaments are primarily composed of this second, \"tense\" form of the monomer. This work is the first time GTP-bound, wild-type FtsZ filaments have been studied directly at atomic resolution and is an important step forward for the study of FtsZ filaments.

Elevated γ-glutamyl transferase (γ-GTP) level is associated with metabolic syndrome, impaired glucose tolerance, and insulin resistance, which are risk factors for type 2 diabetes. We aimed to investigate the association of cumulative exposure to high γ-GTP level with risk of diabetes.
Using nationally representative data from the Korean National Health Insurance system, 346,206 people who were free of diabetes and who underwent 5 consecutive health examinations from 2005 to 2009 were followed to the end of 2018. High γ-GTP level was defined as those in the highest quartile, and the number of exposures to high γ-GTP level ranged from 0 to 5. Hazard ratio (HR) and 95% confidence interval (CI) for diabetes were analyzed using the multivariable Cox proportional-hazards model.
The mean follow-up duration was 9.2±1.0 years, during which 15,183 (4.4%) patients developed diabetes. There was a linear increase in the incidence rate and the risk of diabetes with cumulative exposure to high γ-GTP level. After adjusting for possible confounders, the HR of diabetes in subjects with five consecutive high γ-GTP levels were 2.60 (95% CI, 2.47 to 2.73) in men and 3.05 (95% CI, 2.73 to 3.41) in women compared with those who never had a high γ-GTP level. Similar results were observed in various subgroup and sensitivity analyses.
There was a linear relationship between cumulative exposure to high γ-GTP level and risk of diabetes. Monitoring and lowering γ-GTP level should be considered for prevention of diabetes in the general population.