LLaSM: Large Language and Speech Model

Multi-modal large language models have garnered significant interest recently. Though, most of the works focus on vision-language multi-modal models providing strong capabilities in following vision-and-language instructions. However, we claim that speech is also an important modality through which humans interact with the world. Hence, it is crucial for a general-purpose assistant to be able to follow multi-modal speech-and-language instructions. In this work, we propose Large Language and Speech Model (LLaSM). LLaSM is an end-to-end trained large multi-modal speech-language model with cross-modal conversational abilities, capable of following speech-and-language instructions. Our early experiments show that LLaSM demonstrates a more convenient and natural way for humans to interact with artificial intelligence. Specifically, we also release a large Speech Instruction Following dataset LLaSM-Audio-Instructions. Code and demo are available at https://github.com/LinkSoul-AI/LLaSM and https://huggingface.co/spaces/LinkSoul/LLaSM. The LLaSM-Audio-Instructions dataset is available at https://huggingface.co/datasets/LinkSoul/LLaSM-Audio-Instructions

Mapping the Peds QLTM 4.0 onto CHU-9D: a cross-sectional study in functional dyspepsia population from China

ObjectiveThe study aims to develop a mapping algorithm from the Pediatric Quality of Life Inventory™ 4. 0 (Peds QL 4.0) onto Child Health Utility 9D (CHU-9D) based on the cross-sectional data of functional dyspepsia (FD) children and adolescents in China.MethodsA sample of 2,152 patients with FD completed both the CHU-9D and Peds QL 4.0 instruments. A total of six regression models were used to develop the mapping algorithm, including ordinary least squares regression (OLS), the generalized linear regression model (GLM), MM-estimator model (MM), Tobit regression (Tobit) and Beta regression (Beta) for direct mapping, and multinomial logistic regression (MLOGIT) for response mapping. Peds QL 4.0 total score, Peds QL 4.0 dimension scores, Peds QL 4.0 item scores, gender, and age were used as independent variables according to the Spearman correlation coefficient. The ranking of indicators, including the mean absolute error (MAE), root mean squared error (RMSE), adjusted R2, and consistent correlation coefficient (CCC), was used to assess the predictive ability of the models.ResultsThe Tobit model with selected Peds QL 4.0 item scores, gender and age as the independent variable predicted the most accurate. The best-performing models for other possible combinations of variables were also shown.ConclusionThe mapping algorithm helps to transform Peds QL 4.0 data into health utility value. It is valuable for conducting health technology evaluations within clinical studies that have only collected Peds QL 4.0 data

Characteristic Compounds Identification and Authenticity Evaluation of Heptapleurum Honey

In order to clarify the characteristic compounds and establish the authenticity evaluation method of heptapleurum honey, high-performance liquid chromatography coupled with quadrupole-time-of-flight tandem mass spectrometry (HPLC-Q/TOF-MS/MS) was used to qualitative and quantitative analysis of characteristic compounds in heptapleurum honey. Five compounds were identified including 4-(1'-cyclodiethyl ether-3'-butanediol)-3,5,5-trimethyl-2-cyclohexenone (Unedone B), 3,4,5-trimethoxy cinnamyl alcohol, 4-(1'2'-dihydroxy-3'epoxypropane) -3,5,5-2-cyclohexenone (Unedone C), trans, trans abscisic acid, and cis, trans abscisic acid. Notably, 3,4,5-trimethoxy cinnamyl alcohol was first found in honey, and it could be a marker of heptapleurum honey. Moreover, 10 raw heptapleurum honey samples with different geographic origins were collected to establish HPLC fingerprint. The authenticity of six commercial heptapleurum honey samples were evaluated by combining characteristic compound with HPLC fingerprint. The results demonstrated that three brands of sample were genuine pure heptapleurum honey, two brands of sample might be mixed with other honeys. A brand sample did not contain characteristic compound and were significantly different with the standard fingerprints of heptapleurum honey. It was inferred that the sample was not heptapleurum honey. This study provides theoretical reference for the authenticity evaluation of heptapleurum honey

Research Progress on Extraction, Purification and Biological Activities of Sugarcane Polyphenols

Sugarcane is the most vital sugar crop in China, with excellent nutritional, medicinal and economic value. Sugarcane is rich in phenolic compounds, which have a variety of physiological functions, such as antioxidant, anti-inflammatory, and hypoglycemic. This paper focuses on the extraction of sugarcane polyphenols and the application of novel extraction techniques to plant polyphenols. In addition, principles and properties of purification methods for sugarcane polyphenols are presented, and important biological activities including antioxidant, hypoglycaemic, anti-inflammatory, anti-cancer and anti-bacterial properties are described. The extraction and purification of sugarcane polyphenols is found to be relatively routine. Although sugarcane polyphenols have a variety of biological activities, the mechanisms of their activity have not been fully elucidated. There is a need to focus on new extraction and purification techniques for sugarcane polyphenols and mechanisms of their activity to facilitate the development and utilization of sugarcane polyphenols and deep processing of sugarcane byproducts

Research on the association mechanism and evaluation model between fNIRS data and aesthetic quality in product aesthetic quality evaluation

Aesthetic quality evaluation has been an important research question in the field of user experience in product design. However, the feasibility and accuracy of using fNIRS data for product aesthetic quality evaluation are unknown. In this paper, we analyze the correlation and association between fNIRS data and aesthetic quality and designed a product aesthetic quality evaluation model to answer this question. We find that HBO2 data in the prefrontal (S19-D11), frontal (S4-D3), temporal (S3-D1), and parietal (S8-D8) regions of the brain have significant correlations and logistic relationships with high visual product aesthetic quality, whereas HBO2 data in the prefrontal (S19-D11) and parietal (S8-D8) regions of the brain have significant correlations and association relationships. These data can be used for products aesthetic quality evaluation. Importantly, the overall prediction accuracy of the model to evaluate products’ aesthetic quality is 84.1%. The model is therefore able to better distinguish and evaluate the aesthetic quality of products. This study demonstrates the feasibility of using fNIRS data to evaluate the aesthetic quality of products and shows that the product aesthetic quality evaluation model can provide an objective and accurate decision-making reference to help designers evaluate and improve the aesthetic quality of products

Targeting TNF/IL-17/MAPK pathway in h<i>E2A-PBX1</i> leukemia: effects of OUL35, KJ-Pyr-9, and CID44216842

t(1;19)(q23;p13) is one of the most common translocation genes in childhood acute lymphoblastic leukemia (ALL) and is also present in acute myeloid leukemia (AML) and mixed-phenotype acute leukemia (MPAL). This translocation results in the formation of the oncogenic E2A-PBX1 fusion protein, which contains a trans-activating domain from E2A and a DNA-binding homologous domain from PBX1. Despite its clear oncogenic potential, the pathogenesis of E2A-PBX1 fusion protein is not fully understood (especially in leukemias other than ALL), and effective targeted clinical therapies have not been developed. To address this, we established a stable and heritable zebrafish line expressing human E2A-PBX1 (hE2APBX1) for high-throughput drug screening. Blood phenotype analysis showed that hE2APBX1 expression induced myeloid hyperplasia by increasing myeloid differentiation propensity of hematopoietic stem cells (HSPCs) and myeloid proliferation in larvae, and progressed to AML in adults. Mechanistic studies revealed that hE2A-PBX1 activated the TNF/IL-17/MAPK signaling pathway in blood cells and induced myeloid hyperplasia by upregulating the expression of the runx1. Interestingly, through high-throughput drug screening, three small molecules targeting the TNF/IL-17/MAPK signaling pathway were identified, including OUL35, KJ-Pyr-9, and CID44216842, which not only alleviated the hE2A-PBX1- induced myeloid hyperplasia in zebrafish but also inhibited the growth and oncogenicity of human pre-B ALL cells with E2A-PBX1. Overall, this study provides a novel hE2A-PBX1 transgenic zebrafish leukemia model and identifies potential targeted therapeutic drugs, which may offer new insights into the treatment of E2A-PBX1 leukemia

NAT10 Maintains OGA mRNA Stability Through ac4C Modification in Regulating Oocyte Maturation

In vitro maturation (IVM) refers to the process of developing immature oocytes into the mature in vitro under the microenvironment analogous to follicle fluid. It is an important technique for patients with polycystic ovary syndrome and, especially, those young patients with the need of fertility preservation. However, as the mechanisms of oocyte maturation have not been fully understood yet, the cultivation efficiency of IVM is not satisfactory. It was confirmed in our previous study that oocyte maturation was impaired after N-acetyltransferase 10 (NAT10) knockdown (KD). In the present study, we further explored the transcriptome alteration of NAT10-depleted oocytes and found that O-GlcNAcase(OGA) was an important target gene for NAT10-mediated ac4C modification in oocyte maturation. NAT10 might regulate OGA stability and expression by suppressing its degradation. To find out whether the influence of NAT10-mediated ac4C on oocyte maturation was mediated by OGA, we further explored the role of OGA in IVM. After knocking down OGA of oocytes, oocyte maturation was inhibited. In addition, as oocytes matured, OGA expression increased and, conversely, O-linked N-acetylglucosamine (O-GlcNAc) level decreased. On the basis of NAT10 KD transcriptome and OGA KD transcriptome data, NAT10-mediated ac4C modification of OGA might play a role through G protein–coupled receptors, molecular transduction, nucleosome DNA binding, and other mechanisms in oocyte maturation. Rsph6a, Gm7788, Gm41780, Trpc7, Gm29036, and Gm47144 were potential downstream genes. In conclusion, NAT10 maintained the stability of OGA transcript by ac4C modification on it, thus positively regulating IVM. Moreover, our study revealed the regulation mechanisms of oocytes maturation and provided reference for improving IVM outcomes. At the same time, the interaction between mRNA ac4C modification and protein O-GlcNAc modification was found for the first time, which enriched the regulation network of oocyte maturation

Incidence, clinical characteristics and prognosis of tumor lysis syndrome following B-cell maturation antigen-targeted chimeric antigen receptor-T cell therapy in relapsed/refractory multiple myeloma

Background aimsB-cell maturation antigen (BCMA)-targeted chimeric antigen receptor-T cell (CAR-T) therapy is used for refractory or relapsed multiple myeloma (r/r MM). However, CAR-T-related tumor lysis syndrome (TLS) has been observed. We aimed to elucidate the incidence, clinical and laboratory characteristics, and prognosis of CAR-T cell-related TLS.MethodsPatients (n=105) with r/r MM treated with BCMA-targeted CAR-T cell therapy were included. Patient characteristics, laboratory parameters, and clinical outcomes were assessed.ResultsEighteen (17.1%) patients developed TLS after BCMA-targeted CAR-T cell therapy. The median time till TLS onset was 8 days. Patients with TLS had steep rise in uric acid (UA), creatinine, and lactate dehydrogenase (LDH) within 6 days following CAR-T cell infusion and presented earlier and persistent escalation of cytokines (C-reactive protein [CRP], interleukin-6 [IL-6], interferon-γ [IFN-γ], and ferritin levels). All 18 patients had cytokine release syndrome (CRS), of which 13 (72.2%) developed grade 3–4 CRS. Three of 18 patients (16.7%) developed immune effector cell-associated neurotoxicity syndrome (ICANS): two patients with grade 1 ICANS and one with grade 2 ICANS. TLS development had a negative effect on the objective response rate (77.8% in the TLS group vs. 95.4% in the non-TLS group, p&lt;0.01). During the median follow-up of 15.1 months, the median PFS was poorer of patients with TLS (median: 3.4 months in the TLS group vs. 14.7 months in the non-TLS group, p&lt;0.001, hazard ratio [HR]=3.5 [95% confidence interval [CI] 1.5–8.5]). Also, TLS development exhibited significant effects on OS (median: 5.0 months in the TLS group vs. 39.8 months in the non-TLS group, p&lt;0.001, hazard ratio [HR]=3.7 [95% CI 1.3–10.3]). TLS was associated with a higher tumor burden, elevated baseline creatinine and UA levels, severe CRS, pronounced CAR-T cell expansion, and corticosteroid use.ConclusionTLS is a frequently observed CAR-T therapy complication and negatively influences clinical response and prognosis. Close monitoring for TLS should be implemented during CAR-T cell therapy, especially for those at high TLS risk