Integrating UMLS Knowledge into Large Language Models for Medical Question Answering

Large language models (LLMs) have demonstrated powerful text generation capabilities, bringing unprecedented innovation to the healthcare field. While LLMs hold immense promise for applications in healthcare, applying them to real clinical scenarios presents significant challenges, as these models may generate content that deviates from established medical facts and even exhibit potential biases. In our research, we develop an augmented LLM framework based on the Unified Medical Language System (UMLS), aiming to better serve the healthcare community. We employ LLaMa2-13b-chat and ChatGPT-3.5 as our benchmark models, and conduct automatic evaluations using the ROUGE Score and BERTScore on 104 questions from the LiveQA test set. Additionally, we establish criteria for physician-evaluation based on four dimensions: Factuality, Completeness, Readability and Relevancy. ChatGPT-3.5 is used for physician evaluation with 20 questions on the LiveQA test set. Multiple resident physicians conducted blind reviews to evaluate the generated content, and the results indicate that this framework effectively enhances the factuality, completeness, and relevance of generated content. Our research demonstrates the effectiveness of using UMLS-augmented LLMs and highlights the potential application value of LLMs in in medical question-answering.Comment: 12 pages, 3 figure

Cluster trajectory of SOFA score in predicting mortality in sepsis

Objective: Sepsis is a life-threatening condition. Sequential Organ Failure Assessment (SOFA) score is commonly used to assess organ dysfunction and predict ICU mortality, but it is taken as a static measurement and fails to capture dynamic changes. This study aims to investigate the relationship between dynamic changes in SOFA scores over the first 72 hours of ICU admission and patient outcomes. Design, setting, and participants: 3,253 patients in the Medical Information Mart for Intensive Care IV database who met the sepsis-3 criteria and were admitted from the emergency department with at least 72 hours of ICU admission and full-active resuscitation status were analysed. Group-based trajectory modelling with dynamic time warping and k-means clustering identified distinct trajectory patterns in dynamic SOFA scores. They were subsequently compared using Python. Main outcome measures: Outcomes including hospital and ICU mortality, length of stay in hospital and ICU, and readmission during hospital stay, were collected. Discharge time from ICU to wards and cut-offs at 7-day and 14-day were taken. Results: Four clusters were identified: A (consistently low SOFA scores), B (rapid increase followed by a decline in SOFA scores), C (higher baseline scores with gradual improvement), and D (persistently elevated scores). Cluster D had the longest ICU and hospital stays, highest ICU and hospital mortality. Discharge rates from ICU were similar for Clusters A and B, while Cluster C had initially comparable rates but a slower transition to ward. Conclusion: Monitoring dynamic changes in SOFA score is valuable for assessing sepsis severity and treatment responsiveness.Comment: 26 pages, 4 figures, 2 table

Influence of D-Amino Acids in Beer on Formation of Uric Acid

Prekomjerna konzumacija piva može dovesti do povećanja koncentracije mokraćne kiseline u serumu, čime se povećava rizik nastanka uričnog artritisa (gihta), što se prethodno dovodilo u vezu s velikim udjelom purina u pivu. Međutim, novija istraživanja pokazuju da konzumacija povrća bogatog purinima i grahorica ne povećava koncentraciju mokraćne kiseline, što opovrgava tu tvrdnju. Još uvijek nije objašnjeno zašto povećana konzumacija piva može povećati rizik nastanka gihta, pa su ispitani drugi uzročnici nakupljanja mokraćne kiseline u krvi. Pivo sadržava relativno velike koncentracije D-aminokiselina koje nastaju racemizacijom L-aminokiselina tijekom prerade hrane. Katalizom pomoću D-aminokiselinske oksidaze iz D-aminokiselina nastaje H2O2, čijom oksidacijom u prisutnosti Fe2+ nastaju hidroksilni radikali. Pritom dolazi do oštećenja DNA i nastanka purinskih baza u većoj količini, iz kojih djelovanjem različitih enzima nastaje mokraćna kiselina. Neki dodaci hrani, kao što su vitamini i ioni joda, potiču nastanak mokraćne kiseline iz D-aminokiselina. D-aminokiseline u pivu imaju ključnu ulogu u povećanju koncentracije mokraćne kiseline. Biološka uloga D-aminokiselina može objasniti pojavu gihta kod osoba koje učestalo konzumiraju pivo.Excessive intake of beer could increase serum uric acid levels, leading to high risk of gout, which was previously attributed to high purine content in beer. Recent reports that purine-rich vegetables and bean products do not cause higher uric acid levels do not support this theory. Why excessive intake of beer could increase a high risk of gout has been unclear. Other factors affecting the accumulation of uric acid in the blood have been explored. Beer contains relatively high levels of D-amino acids due to the racemization of l-amino acids induced by food processing. D-amino acid was catalyzed by D-amino acid oxidase to produce H2O2, which is further oxidized in the presence of Fe2+ to produce hydroxyl radicals, resulting in DNA damage and formation of a large amount of purine bases, which are oxidized to uric acid by a series of enzymes. Some food ingredients, such as vitamins and I–, prompt D-amino acids to form uric acid. D-amino acids in beer are one of the key factors responsible for the increase in uric acid levels. The biological response of D-amino acids could explain gout occurrence in beer drinkers

Aquatic environmental changes and ecological implications from the combined effects of sea-level rise and land reclamation in Deep Bay, Pearl River Estuary, China

Objectives By analyzing the different phenotypes of two Chinese DFNA9 families with the same mutation located in the intervening region between the LCCL and vWFA domains of cochlin and testing the functional changes in the mutant cochlin, we investigated the different pathogeneses for mutations in LCCL and vWFA domains. Methods Targeted next-generation sequencing for deafness-related genes was used to identify the mutation in the proband in family #208. The probands of family #208 and family #32 with the same p.C162 Upsilon mutation were followed for more than 3 years to evaluate the progression of hearing loss and vestibular dysfunction using pure-tone audiometry, caloric testing, electrocochleogram, vestibular-evoked myogenic potential, and video head-impulse test. The disruption of normal cleavage to produce secreted LCCL domain fragments and the tendency to form aggregations of mutant cochlins were tested by in vitro cell experiments. Results The two families showed different clinical symptoms. Family #32 was identified as having early-onset, progressive sensorineural hearing loss, similar to the symptoms in DFNA9 patients with cochlin mutations in the vWFA domain. The proband of family #208 endured late-onset recurrent paroxysmal vertigo attacks and progressively deteriorating hearing, similar to symptoms in those with cochlin mutations in the LCCL domain. We therefore suggest that the disrupted cleavage of the LCCL domain fragment is likely to cause vestibular dysfunction, and aggregation of mutant cochlin caused by mutations in the vWFA domain is responsible for early-onset hearing loss. The p.C162 Upsilon mutation causes either disruption of LCCL domain fragment cleavage or aggregation of mutant cochlin, resulting in the different phenotypes in the two families. Conclusion This study demonstrates that DFNA9 families with the same genotype may have significantly different phenotypes. The mutation site in cochlin is related to the pathological mechanism underlying the different phenotypes.National Natural Science Foundation of China [81271083, 81470691]SCI(E)ARTICLE11

A "Wait-and-See" Approach to Quiescent Single-System Langerhans Cell Histiocytosis to Spare Children From Chemotherapy

10.3389/fped.2020.00466FRONTIERS IN PEDIATRICS

Strain Engineering and Halogen Compensation of Buried Interface in Polycrystalline Halide Perovskites

Inverted perovskite solar cells based on weakly polarized hole-transporting layers suffer from the problem of polarity mismatch with the perovskite precursor solution, resulting in a nonideal wetting surface. In addition to the bottom-up growth of the polycrystalline halide perovskite, this will inevitably worse the effects of residual strain and heterogeneity at the buried interface on the interfacial carrier transport and localized compositional deficiency. Here, we propose a multifunctional hybrid pre-embedding strategy to improve substrate wettability and address unfavorable strain and heterogeneities. By exposing the buried interface, it was found that the residual strain of the perovskite films was markedly reduced because of the presence of organic polyelectrolyte and imidazolium salt, which not only realized the halogen compensation and the coordination of Pb2+ but also the buried interface morphology and defect recombination that were well regulated. Benefitting from the above advantages, the power conversion efficiency of the targeted inverted devices with a bandgap of 1.62 eV was 21.93% and outstanding intrinsic stability. In addition, this coembedding strategy can be extended to devices with a bandgap of 1.55 eV, and the champion device achieved a power conversion efficiency of 23.74%. In addition, the optimized perovskite solar cells retained 91% of their initial efficiency (960 h) when exposed to an ambient relative humidity of 20%, with a T80 of 680 h under heating aging at 65 °C, exhibiting elevated durability

DE-71-induced apoptosis involving intracellular calcium and the Bax-mitochondria-caspase protease pathway in human neuroblastoma cells In vitro

Polybrominated diphenyl ethers (PBDEs) are used extensively as flame-retardants and are ubiquitous in the environment and in wildlife and human tissue. Recent studies have shown that PBDEs induce neurotoxic effects in vivo and apoptosis in vitro. However, the signaling mechanisms responsible for these events are still unclear. In this study, we investigated the action of a commercial mixture of PBDEs (pentabrominated diphenyl ether, DE-71) on a human neuroblastoma cell line, SK-N-SH. A cell viability test showed a dose-dependent increase in lactate dehydrogenase leakage and 3-(4,5-dimethylthia-zol-2-yl)-2,5-diphenyl-tetrazolium bromide reduction. Cell apoptosis was observed through morphological examination, and DNA degradation in the cell cycle and cell apoptosis were demonstrated using flow cytometry and DNA laddering. The formation of reactive oxygen species was not observed, but DE-71 was found to significantly induce caspase-3, -8, and -9 activity, which suggests that apoptosis is not induced by oxidative stress but via a caspase-dependent pathway. We further investigated the intracellular calcium ([Ca2+](i)) levels using flow cytometry and observed an increase in the intracellular Ca2+ concentration with a time-dependent trend. We also found that the N-methyl d-aspartate (NMDA) receptor antagonist MK801 (3 mu M) significantly reduced DE-71-induced cell apoptosis. The results of a Western blotting test demonstrated that DE-71 treatment increases the level of Bax translocation to the mitochondria in a dose-dependent fashion and stimulates the release of cytochrome c (Cyt c) from the mitochondria into the cytoplasm. Overall, our results indicate that DE-71 induces the apoptosis of ([Ca2+](i)) in SK-N-SH cells via Bax insertion, Cyt c release in the mitochondria, and the caspase activation pathway.Polybrominated diphenyl ethers (PBDEs) are used extensively as flame-retardants and are ubiquitous in the environment and in wildlife and human tissue. Recent studies have shown that PBDEs induce neurotoxic effects in vivo and apoptosis in vitro. However, the signaling mechanisms responsible for these events are still unclear. In this study, we investigated the action of a commercial mixture of PBDEs (pentabrominated diphenyl ether, DE-71) on a human neuroblastoma cell line, SK-N-SH. A cell viability test showed a dose-dependent increase in lactate dehydrogenase leakage and 3-(4,5-dimethylthia-zol-2-yl)-2,5-diphenyl-tetrazolium bromide reduction. Cell apoptosis was observed through morphological examination, and DNA degradation in the cell cycle and cell apoptosis were demonstrated using flow cytometry and DNA laddering. The formation of reactive oxygen species was not observed, but DE-71 was found to significantly induce caspase-3, -8, and -9 activity, which suggests that apoptosis is not induced by oxidative stress but via a caspase-dependent pathway. We further investigated the intracellular calcium ([Ca2+](i)) levels using flow cytometry and observed an increase in the intracellular Ca2+ concentration with a time-dependent trend. We also found that the N-methyl d-aspartate (NMDA) receptor antagonist MK801 (3 mu M) significantly reduced DE-71-induced cell apoptosis. The results of a Western blotting test demonstrated that DE-71 treatment increases the level of Bax translocation to the mitochondria in a dose-dependent fashion and stimulates the release of cytochrome c (Cyt c) from the mitochondria into the cytoplasm. Overall, our results indicate that DE-71 induces the apoptosis of ([Ca2+](i)) in SK-N-SH cells via Bax insertion, Cyt c release in the mitochondria, and the caspase activation pathway