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Backgrounds Traditional methods of teaching history-taking in medical education are limited by scalability and resource intensity. This study aims to assess the effectiveness of simulated patient interactions based on a custom-designed Generative Pre-trained Transformer (GPT) model, developed using OpenAI’s ChatGPT GPTs platform, in enhancing medical students’ history-taking skills compared to traditional role-playing methods. Methods A total of 56 medical students were randomly assigned into two groups: an GPT group using GPT-simulated patients and a control group using traditional role-playing. Pre- and post-training assessments were conducted using a structured clinical examination to measure students’ abilities in history collection, clinical reasoning, communication skills, and professional behavior. Additionally, students’ evaluations of the educational effectiveness, satisfaction, and recommendation likelihood were assessed. Results The GPT-simulation group showed significantly higher post-training scores in the structured clinical examination compared to the control group (86.79 ± 5.46,73.64 ± 4.76, respectively, P  < 0.001). Students in the GPT group exhibited higher enthusiasm for learning, greater self-directed learning motivation, and better communication feedback abilities compared to the control group ( P  < 0.05). Additionally, the student satisfaction survey revealed that the GPT group rated higher on the diversity of diseases encountered, ease of use, and likelihood of recommending the training compared to the control group ( P  < 0.05). Conclusions GPT-based history-taking training effectively enhances medical students’ history-taking skills, providing a solid foundation for the application of artificial intelligence (AI) in medical education. Clinical trial number NCT06766383.

Resident microbiota activate regulatory cells that modulate intestinal inflammation and promote and maintain intestinal homeostasis. IL-10 is a key mediator of immune regulatory function. Our studies described the functional importance and mechanisms by which gut microbiota and specific microbial components influenced the development of intestinal IL-10-producing B cells. We used fecal transplant to germ-free (GF) Il10+/EGFP reporter and Il10-/- mice to demonstrate that microbiota from specific pathogen-free mice primarily stimulated IL-10-producing colon-specific B cells and T regulatory-1 cells in ex-GF mice. IL-10 in turn down-regulated microbiota-activated mucosal inflammatory cytokines. TLR2/9 ligands and enteric bacterial lysates preferentially induced IL-10 production and regulatory capacity of intestinal B cells. Analysis of Il10+/EGFP mice crossed with additional gene-deficient strains and B cell co-transfer studies demonstrated that microbiota-induced IL-10-producing intestinal B cells ameliorated chronic T cell-mediated colitis in a TLR2, MyD88 and PI3K-dependent fashion. In vitro studies implicated PI3Kp110δ and AKT downstream signaling. These studies demonstrated that resident enteric bacteria activated intestinal IL-10-producing B cells through TLR2, MyD88 and PI3K pathways. These B cells reduced colonic T cell activation and maintained mucosal homeostasis in response to intestinal microbiota.

Environmental factors, mucosal permeability and defective immunoregulation drive overactive immunity to a subset of resident intestinal bacteria that mediate multiple inflammatory conditions. GUT-103 and GUT-108, live biotherapeutic products rationally designed to complement missing or underrepresented functions in the dysbiotic microbiome of IBD patients, address upstream targets, rather than targeting a single cytokine to block downstream inflammation responses. GUT-103, composed of 17 strains that synergistically provide protective and sustained engraftment in the IBD inflammatory environment, prevented and treated chronic immune-mediated colitis. Therapeutic application of GUT-108 reversed established colitis in a humanized chronic T cell-mediated mouse model. It decreased pathobionts while expanding resident protective bacteria; produced metabolites promoting mucosal healing and immunoregulatory responses; decreased inflammatory cytokines and Th-1 and Th-17 cells; and induced interleukin-10-producing colonic regulatory cells, and IL-10-independent homeostatic pathways. We propose GUT-108 for treating and preventing relapse for IBD and other inflammatory conditions characterized by unbalanced microbiota and mucosal permeability. Fecal microbiota transplantation and probiotics have been tested/used as potential therapeutics against inflammatory bowel diseases (IBD). Here the authors use a bottom-up rational consortium design approach that combines well-characterized strains isolated from healthy human stool samples to produce two consortia of metabolically interdependent strains for the treatment of IBD.

ObjectiveThe gut microbiota has been suggested to play a role in autism spectrum disorder (ASD). We postulate that children with ASD harbour an altered developmental profile of the gut microbiota distinct from that of typically developing (TD) children. Here, we aimed to characterise compositional and functional alterations in gut microbiome in association with age in children with ASD and to identify novel faecal bacterial markers for predicting ASD.DesignWe performed deep metagenomic sequencing in faecal samples of 146 Chinese children (72 ASD and 74 TD children). We compared gut microbial composition and functions between children with ASD and TD children. Candidate bacteria markers were identified and validated by metagenomic analysis. Gut microbiota development in relation to chronological age was assessed using random forest model.ResultsASD and chronological age had the most significant and largest impacts on children’s faecal microbiome while diet showed no correlation. Children with ASD had significant alterations in faecal microbiome composition compared with TD children characterised by increased bacterial richness (p=0.021) and altered microbiome composition (p<0.05). Five bacterial species were identified to distinguish gut microbes in ASD and TD children, with areas under the receiver operating curve (AUC) of 82.6% and 76.2% in the discovery cohort and validation cohort, respectively. Multiple neurotransmitter biosynthesis related pathways in the gut microbiome were depleted in children with ASD compared with TD children (p<0.05). Developing dynamics of growth-associated gut bacteria (age-discriminatory species) seen in TD children were lost in children with ASD across the early-life age spectrum.ConclusionsGut microbiome in Chinese children with ASD was altered in composition, ecological network and functionality compared with TD children. We identified novel bacterial markers for prediction of ASD and demonstrated persistent underdevelopment of the gut microbiota in children with ASD which lagged behind their respective age-matched peers.

Background The adaption of brain region is fundamental to the development and maintenance of nervous system disorders. The prelimbic cortex (PrL) participates in the affective components of the pain sensation. However, whether and how the adaptation of PrL contributes to the comorbidity of neuropathic pain and depression are unknown. Methods Using resting-state functional magnetic resonance imaging (rs-fMRI), genetic knockdown or overexpression, we systematically investigated the activity of PrL region in the pathogenesis of neuropathic pain/depression comorbid using the combined approaches of immunohistochemistry, electrophysiology, and behavior. Results The activity of PrL and the excitability of pyramidal neurons were decreased, and the osteoclastic tartrate-resistant acid phosphatase 5 (Acp5) expression in PrL neurons was upregulated following the acquisition of spared nerve injury (SNI)-induced comorbidity. Genetic knockdown of Acp5 in pyramidal neurons, but not parvalbumin (PV) neurons or somatostatin (SST) neurons, attenuated the decrease of spike number, depression-like behavior and mechanical allodynia in comorbidity rats. Overexpression of Acp5 in PrL pyramidal neurons decreased the spike number and induced the comorbid-like behavior in naïve rats. Moreover, the expression of interleukin-6 (IL-6), phosphorylated STAT3 (p-STAT3) and acetylated histone H3 (Ac-H3) were significantly increased following the acquisition of comorbidity in rats. Increased binding of STAT3 to the Acp5 gene promoter and the interaction between STAT3 and p300 enhanced acetylation of histone H3 and facilitated the transcription of Acp5 in PrL in the modeled rodents. Inhibition of IL-6/STAT3 pathway prevented the Acp5 upregulation and attenuated the comorbid-like behaviors in rats. Conclusions These data suggest that the adaptation of PrL mediated by IL-6/STAT3/Acp5 pathway contributed to the comorbidity of neuropathic pain/depression induced by SNI.

With the development and regulatory approval of immune checkpoint inhibitors and adoptive cell therapies, cancer immunotherapy has undergone a profound transformation over the past decades. Recently, therapeutic cancer vaccines have shown promise by eliciting de novo T cell responses targeting tumor antigens, including tumor-associated antigens and tumor-specific antigens. The objective was to amplify and diversify the intrinsic repertoire of tumor-specific T cells. However, the complete realization of these capabilities remains an ongoing pursuit. Therefore, we provide an overview of the current landscape of cancer vaccines in this review. The range of antigen selection, antigen delivery systems development the strategic nuances underlying effective antigen presentation have pioneered cancer vaccine design. Furthermore, this review addresses the current status of clinical trials and discusses their strategies, focusing on tumor-specific immunogenicity and anti-tumor efficacy assessment. However, current clinical attempts toward developing cancer vaccines have not yielded breakthrough clinical outcomes due to significant challenges, including tumor immune microenvironment suppression, optimal candidate identification, immune response evaluation, and vaccine manufacturing acceleration. Therefore, the field is poised to overcome hurdles and improve patient outcomes in the future by acknowledging these clinical complexities and persistently striving to surmount inherent constraints.

A pair of stereoisomers possessing novel structures with 6/6/5 fused-ring systems, neo-debromoaplysiatoxin E (1) and neo-debromoaplysiatoxin F (2), were isolated from the marine cyanobacterium Lyngbya sp. Their structures were elucidated using various spectroscopic techniques including high resolution electrospray ionization mass spectroscopy (HRESIMS) and nuclear magnetic resonance (NMR). The absolute stereochemistry was determined by calculated electronic circular dichroism (ECD) and gauge-independent atomic orbital (GIAO) NMR shift calculation followed by DP4+ analysis. Significantly, this is the first report on aplysiatoxin derivatives with different absolute configurations at C9–C12 (1: 9S, 10R, 11S, 12S; 2: 9R, 10S, 11R, 12R). Compounds 1 and 2 exhibited potent blocking activities against Kv1.5 with IC50 values of 1.22 ± 0.22 μM and 2.85 ± 0.29 μM, respectively.

Inflammation alters host physiology to promote cancer, as seen in colitis-associated colorectal cancer (CRC). Here, we identify the intestinal microbiota as a target of inflammation that affects the progression of CRC. High-throughput sequencing revealed that inflammation modifies gut microbial composition in colitis-susceptible interleukin-10—deficient (Il10⁻ / ⁻) mice. Monocolonization with the commensal Escherichia coli NC101 promoted invasive carcinoma in azoxymethane (AOM)—treated Il10⁻ / ⁻ mice. Deletion of the polyketide synthase (pks) genotoxic island from E. coli NC101 decreased tumor multiplicity and invasion in AOM/Il10⁻ / ⁻ mice, without altering intestinal inflammation. Mucosa-associated pks⁺ E. coli were found in a significantly high percentage of inflammatory bowel disease and CRC patients. This suggests that in mice, colitis can promote tumorigenesis by altering microbial composition and inducing the expansion of microorganisms with genotoxic capabilities.

Background Neoadjuvant chemotherapy is a promising treatment option for potential resectable gastric cancer, but patients’ responses vary. We aimed to develop and validate a radiomics score (rad_score) to predict treatment response to neoadjuvant chemotherapy and to investigate its efficacy in survival stratification. Methods A total of 106 patients with neoadjuvant chemotherapy before gastrectomy were included (training cohort: n  = 74; validation cohort: n  = 32). Radiomics features were extracted from the pre-treatment portal venous-phase CT. After feature reduction, a rad_score was established by Randomised Tree algorithm. A rad_clinical_score was constructed by integrating the rad_score with clinical variables, so was a clinical score by clinical variables only. The three scores were validated regarding their discrimination and clinical usefulness. The patients were stratified into two groups according to the score thresholds (updated with post-operative clinical variables), and their survivals were compared. Results In the validation cohort, the rad_score demonstrated a good predicting performance in treatment response to the neoadjuvant chemotherapy (AUC [95% CI] =0.82 [0.67, 0.98]), which was better than the clinical score (based on pre-operative clinical variables) without significant difference (0.62 [0.42, 0.83], P  = 0.09). The rad_clinical_score could not further improve the performance of the rad_score (0.70 [0.51, 0.88], P  = 0.16). Based on the thresholds of these scores, the high-score groups all achieved better survivals than the low-score groups in the whole cohort (all P  < 0.001). Conclusion The rad_score that we developed was effective in predicting treatment response to neoadjuvant chemotherapy and in stratifying patients with gastric cancer into different survival groups. Our proposed strategy is useful for individualised treatment planning.

As sessile organisms, plants are exposed to diverse abiotic and biotic stresses, and thus have developed complex signaling mechanisms that orchestrate multiple stress responses. Plant peptides have recently emerged as key signaling molecules of stress responses, not only to mechanical wounding and pathogen infection but also to nutrient imbalance, drought and high salinity. The currently identified stress-related signaling peptides in plants are derived from proteolytic processing of protein precursors. Here, we review these protein-derived peptides and the evidence for their functions in stress signaling. We recommend potential research directions that could clarify their roles in stress biology, and propose possible crosstalk with regard to the physiological outcome. The stress-centric perspective allows us to highlight the crucial roles of peptides in regulating the dynamics of stress physiology. Inspired by historic and recent findings, we review how peptides initiate complex molecular interactions to coordinate biotic and abiotic stress responses in plants.