Interpretable CT radiomics model for invasiveness prediction in patients with ground-glass nodules.

AIM: To evaluate the performance of an interpretable computed tomography (CT) radiomic model in predicting the invasiveness of ground-glass nodules (GGNs). MATERIALS AND METHODS: The study was conducted retrospectively from 1 August 2017 to 1 August 2022, at three different centres. Two hundred and thirty patients with GGNs were enrolled at centre I as a training cohort. Centres II (n=157) and III (n=156) formed two external validation cohorts. Radiomics features extracted based on CT were reduced by a coarse-fine feature screening strategy. A radiomic model was developed through the use of the LASSO (least absolute shrinkage and selection operator) and XGBoost algorithms. Then, a radiological model was established through multivariate logistic regression analysis. Finally, the interpretability of the model was explored using SHapley Additive exPlanations (SHAP). RESULTS: The radiomic XGBoost model outperformed the radiomic logistic model and radiological model in assessing the invasiveness of GGNs. The area under the curve (AUC) values for the radiomic XGBoost model were 0.885 (95% confidence interval [CI] 0.836-0.923), 0.853 (95% CI 0.790-0.906), and 0.838 (95% CI 0.773-0.902) in the training and the two external validation cohorts, respectively. The SHAP method allowed for both a quantitative and visual representation of how decisions were made using a given model for each individual patient. This can provide a deeper understanding of the decision-making mechanisms within the model and the factors that contribute to its prediction effectiveness. CONCLUSIONS: The present interpretable CT radiomics model has the potential to preoperatively evaluate the invasiveness of GGNs. Furthermore, it can provide personalised, image-based clinical-decision support.

Lipoprotein(a) is associated with recurrent cardiovascular events in patients with coronary artery disease and prediabetes or diabetes.

PURPOSE: Elevated lipoprotein(a) [Lp(a)] and diabetes mellitus (DM) are both associated with adverse events in high-risk patients with established coronary artery disease (CAD). Currently, the association between Lp(a) levels and recurrent cardiovascular (CV) events (CVEs) remained undetermined in patients with different glucose status. Therefore, this study aimed to investigate the prognostic significance of Lp(a) levels for recurrent CVEs in high-risk CAD patients who suffered from first CVEs according to different glycemic metabolism. METHODS: We recruited 5257 consecutive patients with prior CVEs and followed up for recurrent CVEs, including CV death, non-fatal myocardial infarction (MI), and non-fatal stroke. Patients were assigned to low, medium, and high groups according to Lp(a) levels and further stratified by glucose status. RESULTS: During a median 37-month follow-up, 225 (4.28%) recurrent CVEs occurred. High Lp(a) was independently associated with recurrent CVEs [adjusted Hazard Ratio (HR), 1.57; 95% confidence interval (CI) 1.12-2.19; P = 0.008]. When participants were classified according to Lp(a) levels and glycemic status, high Lp(a) levels were associated with an increased risk of recurrent CVEs in pre-DM (adjusted HR, 2.96; 95% CI 1.24-7.05; P = 0.014). Meanwhile, medium and high Lp(a) levels were both associated with an increased risk for recurrent CVEs in DM (adjusted HR, 3.09; 95% CI 1.30-7.34; P = 0.010 and adjusted HR, 3.13, 95% CI 1.30-7.53; P = 0.011, respectively). CONCLUSIONS: This study demonstrated that elevated Lp(a) levels were associated with an increased recurrent CVE risk in patients with CAD, particularly among those with pre-DM and DM, indicating that Lp(a) may provide incremental value in risk stratification in this population.

Biocontrol of strawberry Botrytis gray mold and prolong the fruit shelf-life by fumigant Trichoderma spp.

Objectives To screen high active volatile organic compounds (VOCs)-producing Trichoderma isolates against strawberry gray mold caused by Botrytis cinerea, and to explore their antagonistic mode of action against the pathogen. VOCs produced by nine Trichoderma isolates (Trichoderma atroviride T1 and T3; Trichoderma harzianum T2, T4 and T5; T6, T7, T8 and T9 identified as Trichoderma asperellum in this work) significantly inhibited the mycelial growth (13.9-63.0% reduction) and conidial germination (17.6-96.3% reduction) of B. cinerea, the highest inhibition percentage belonged to VOCs of T7; in a closed space, VOCs of T7 shared 76.9% and 100% biocontrol efficacy against gray mold on strawberry fruits and detached leaves, respectively, prolonged the fruit shelf-life by 3 days in presence of B. cinerea, completely protected the leaves from B. cinerea infecting; volatile metabolites of T7 damaged the cell membrane permeability and integrity of B. cinerea, thereby inhibiting the mycelial growth and conidial germination. Gas chromatography-mass spectrometry (GC-MS) analysis revealed the VOCs contain 23 potential compounds, and the majority of these compounds were categorised as alkenes, alcohols, and esters, including PEA and 6PP, which have been reported as substances produced by Trichoderma spp. T. asperellum T7 showed high biofumigant activity against mycelial growth especially conidial germination of B. cinerea and thus protected strawberry fruits and leaves from gray mold, which acted by damaging the pathogen's plasma membrane and resulting in cytoplasm leakage, was a potential biofumigant for controlling pre- and post-harvest strawberry gray mold.

Vegetation-fire feedbacks increase subtropical wildfire risk in scrubland and reduce it in forests.

Climate dictates wildfire activity around the world. But East and Southeast Asia are an apparent exception as fire-activity variation there is unrelated to climatic variables. In subtropical China, fire activity decreased by 80% between 2003 and 2020 amid increased fire risks globally. Here, we assessed the fire regime, vegetation structure, fuel flammability and their interactions across subtropical Hubei, China. We show that tree basal area (TBA) and fuel flammability explained 60% of fire-frequency variance. Fire frequency and fuel flammability, in turn, explained 90% of TBA variance. These results reveal a novel system of scrubland-forest stabilized by vegetation-fire feedbacks. Frequent fires promote the persistence of derelict scrubland through positive vegetation-fire feedbacks; in forest, vegetation-fire feedbacks are negative and suppress fire. Thus, we attribute the decrease in wildfire activity to reforestation programs that concurrently increase forest coverage and foster negative vegetation-fire feedbacks that suppress wildfire.

Genetic analysis of a Kaijiang duck conservation population through genome-wide scan.

1. The Kaijiang duck is a native Chinese breed known for its excellent egg laying performance, killing-out percentage (88.57%), and disease resistance. The assessment of population genetic structure is the basis for understanding the genetics of indigenous breeds and for their protection and management.2. In this study, whole-genome sequencing was performed on 60 Kaijiang ducks to identify genetic variations and investigate the population structure. Homozygosity (ROH) analysis was conducted to assess inbreeding levels in the population.3. The study revealed a moderate level of inbreeding, indicated by an average inbreeding coefficient of 0.1043. This may impact the overall genetic diversity.4. Genomic Regions of Interest identified included 168 genomic regions exhibiting high levels of autozygosity. These regions were associated with processes including muscle growth, pigmentation, neuromodulation, and growth and reproduction.5. The significance of these pathways indicated their potential role in shaping the desirable traits of the Kaijiang duck. These findings provide insights into the genetic basis of the Kaijiang duck's desirable traits and can inform future breeding and conservation efforts.

[The influence of Ras-associated binding protein 23 knockdown on the migration and invasion of esophageal squamous cell carcinoma cells and its mechanism].

Objective: To investigate the role and the mechanism of Ras-associated binding protein23 (RAB23) in the migration and invasion of esophageal squamous cell carcinoma (ESCC) cells. Methods: RAB23 mRNA levels were measured in 16 pairs of ESCC and adjacent normal tissues via real-time polymerase chain reactions. RAB23 mRNA levels in the ESCC and adjacent normal tissues of dataset GSE20347 deposited in the Gene Expression Omnibus (GEO) database were also analyzed. Immunohistochemistry (IHC) was used to detect the RAB23 protein expressions in 106 pairs of ESCC and adjacent normal tissues, as well as in the lymph glands and primary tumor tissues of 33 patients with positive lymph nodes and 10 patients with negative lymph nodes. Endogenous RAB23 expression was transiently depleted using siRNAs (si-NC, si-RAB23-1, and si-RAB23-9) or stably reduced using shRNAs (sh-NC and sh-RAB23) in ESCC KYSE30 and KYSE150 cells, and the knockdown efficiency was tested using Western blot assays. Cell counting kit-8 assays and mouse xenograft models were used to test the proliferation of ESCC cells. Transwell assays and tail vein-pulmonary metastasis models in immunocompromised mice were used to examine the migration and invasion of ESCC cells. Cell adhesion assays were used to test the adhesion of ESCC cells. RNA-seq assays were used to analyze how RAB23 knockdown influenced the expression profile of ESCC cells and the implicated signal pathways were confirmed using Western blot assays. Results: The RAB23 mRNA expression in 16 cases of ESCC tissues was 0.009 7±0.008 9, which was markedly higher than that in adjacent normal tissues (0.003 2±0.003 7, P=0.006). GEO analysis on RAB23 expressions in ESCC and adjacent normal tissues showed that the RAB23 mRNA level in ESCC tissues (4.30±0.25) was remarkably increased compared with their normal counterparts (4.10±0.17, P=0.037). Among the 106 pairs of ESCC and tumor-adjacent normal tissues, 51 cases exhibited low expression of RAB23 and 55 cases showed high expression of RAB23, whereas in the paired tumor-adjacent normal tissues 82 cases were stained weakly and 24 strongly for RAB23 protein. These results indicated that RAB23 expression was markedly increased in ESCC tissues (P<0.001). Additionally, only 1 out of 33 primary ESCC tissues with positive lymph nodes showed low RAB23 protein expression. On the other hand, 7 samples of primary ESCC tissues with negative lymph nodes were stained strongly for RAB23 while its level in the other 3 samples was weak. These results showed that RAB23 expression was remarkably increased in primary ESCC tissues with positive lymph nodes compared with those with negative lymph nodes (P=0.024). Further tests showed that 32 out of 33 positive lymph nodes were stained strongly for RAB23, whereas no negative lymph nodes (n=10) exhibited high expression of RAB23 (P<0.001). Both transient and stable knockdown of endogenous RAB23 expression failed to cause detectable changes in the proliferation of KYSE30 cells in vitro and in vivo, but attenuated the migration and invasion of KYSE30 cells as well as the invasion of KYSE150 cells. RAB23 knockdown was found to significantly decrease the number of adhesive KYSE30 cells in the sh-RAB23 group (313.75±89.34) compared with control cells in the sh-NC group (1 030.75±134.29, P<0.001). RAB23 knockdown was also found to significantly decrease the number of adhesive KYSE150 cells in the sh-RAB23 group (710.5±31.74) compared with the number of control cells in the sh-NC group (1 005.75±61.09, P<0.001). RNA-seq assays demonstrated that RAB23 knockdown using two siRNAs targeting RAB23 mRNA markedly impaired focal adhesion-related signal pathways, and decreased the levels of phosphorylated FAK (p-FAK) and phosphorylated paxillin (p-paxillin) in KYSE30 and KYSE150 cells. Conclusions: Significantly increased RAB23 in ESCC tissues positively correlates with lymph node metastasis. Depleted RAB23 expression attenuates focal adhesion-related signal pathways, thus impairing the invasion, metastasis, and adhesion of ESCC cells.

[Standardization of next-generation sequencing for detecting mutations associated with targeted therapy and immunotherapy based on dynamic pattern of expandable detection range].

Next-generation sequencing (NGS) has laid the foundation for precision oncology care. NGS technologynot only represents an innovation in the methodology but also brings about a revolution in the concept of detecting gene alterations for targeted therapy and immunotherapy of cancers. As basic biomedical research and drug development progress, the landscape of biomarkers associated with gene alterations continues to evolve. Thus, the standardization of NGS-based gene alterations detection should take into account the characteristics of NGS methods and the gene alteration biomarkers. To be specific, whether employed as in vitro diagnostic products or laboratory-developed tests, the detection range can be expanded in response to changes in the clinical evidence level of biomarkers during the process of assay development and clinical application. Such adjustment needs the analytical validation results for supplemented genes or mutant sites within a predefined detection system, which will maximally fulfill the evolving clinical demands in cancer diagnosis and treatment, simultaneously mitigate potential risks effectively. This article primarily discusses the standardization pathway for NGS testing of gene alterations in cancer by focusing on the characteristics of NGS methods, gene alteration biomarkers, and the current status of the standardization of NGS application.

[The prognostic evaluation of coronary artery calcification score and CT fractional flow reserve for patients with stable coronary artery disease].

Objective: To investigate the prognostic value of coronary artery calcium score (CACS) and computed tomography-derived fractional flow reserve (CT-FFR) for major adverse cardiovascular events (MACE) in patients with stable coronary artery disease (CAD). Methods: The data for this prospective study were derived from a prospective clinical trial at a single center. This trial enrolled stable CAD patients who underwent coronary CT angiography (CCTA) in General Hospital of Eastern Theater Command from April 2018 to March 2019 and had coronary artery stenosis of 25%-80%. Patients were assigned to either the control group or trial group according to CCTA time. Patients in control group were provided with only a standard CCTA report, while patients in trial group were provided with both a standard CCTA report and the corresponding CT-FFR results. The study included patients who underwent ECG-gated calcium scoring CT scans in this trial. CT-FFR value at 2 cm distal to the narrowest stenosis of each vessel was calculated. The minimum CT-FFR value was recorded as the patient level and CT-FFR≤0.80 was defined as a positive result. All patients were followed up for MACE, including all-cause death, nonfatal myocardial infarction, and acute coronary syndrome leading to unplanned revascularization. Multivariable Cox proportional hazards regression analysis was used to identify variables associated with MACE occurrence, and the Concordance index (C-index) was used to represent the performance of the models for predicting MACE occurrence based on clinical, anatomical, and CT-FFR parameters. Results: A total of 783 patients were finally statistically analyzed, with a age of (62.0±10.8) years, of whom 64.6% (506 cases) were male. There were 383 patients in the trial group and 400 patients in the control group, with a median follow-up time of 35.3 months. A total of 81 MACE cases occurred during the follow-up. The incidence of MACE in trial group (8.1%, 31/383) was significantly lower than that in control group (12.5%, 50/400)(χ2=4.095, P=0.043). CACS≥300, stenosis≥70% and CT-FFR≤0.80 [HR (95%CI) were 2.14 (1.01-4.52), 5.38 (3.44-8.42) and 16.91 (9.21-31.04), all P<0.05] showed predictive value for MACE. The predictive ability of the CT-FFR model is significantly better than that of the CACS model and the stenosis degree model [C-index (95%CI) were 0.850 (0.823-0.874), 0.653 (0.618-0.686) and 0.718 (0.685-0.749), all P≤0.001]. The comprehensive model with added CACS and stenosis degree did not significantly improve the predictive value of the CT-FFR model [C-index (95%CI) were 0.867 (0.841-0.890), 0.850 (0.823-0.874), P=0.584]. Conclusions: CT-FFR has a high predictive value for MACE in patients with stable CAD, the combination of CT-FFR and CACS did not increase the predictive power of CT-FFR.

[Effect of plasminogen activator urokinase receptor gene on the activation and apoptosis of neutrophil].

Objective: To investigate the effect of plasminogen activator urokinase receptor (PLAUR) gene on neutrophil activation and apoptosis in neutrophil-like cell model. Methods: Human acute myeloid leukemia cell line HL60 was cultured in vitro and induced to differentiate into neutrophil-like cells by all-trans retinoic acid (ATRA). Lentiviral vectors interfering with human PLAUR gene was constructed and transfected into neutrophil-like cells (siRNA group). The phosphate buffer saline (PBS) group (untransfected neutrophil-like cells) and normal blank control group (NC group) (neutrophil-like cells transfected with blank plasmid) were used as controls (n=3). After starvation culture and addition of interleukin-17 afterwards in these 3 groups, the expression of CD11b on the cell membrane was detected by flow cytometry, and the levels of myeloperoxide (MPO) and extracellular neutrophil traps (NETs) in the supernatant were detected by enzyme-linked immunosorbent assay (ELISA) to investigate the activation of neutrophil-like cells. The apoptosis was detected by flow cytometry with annexin V/propidium iodide (PI) double staining and the expressions of apoptosis-related proteins caspase-3, bax and bcl-2 were detected by Western blotting. Results: The expression of CD11b in siRNA group (32.37±8.17) was lower than that in PBS group (46.27±1.54) and NC group (53.07±8.14) (P<0.05) by flow cytometry. The levels of MPO and NETs (33.37±1.11, 57.69±3.03) in the supernatant of siRNA group were significantly lower than those in PBS group (41.64±2.20, 77.60±4.33) and NC group (40.84±5.11, 76.15±2.10) (P<0.05). Flow cytometry with annexin V/PI showed that the expression of apoptosis in siRNA group (20.42%±2.45%) was significantly higher than that in PBS group (11.91%±2.23%) and NC group (11.13%±2.56%) (P<0.05). The relative expression of caspase-3 protein and bax protein (0.84±0.05, 0.83±0.04) in siRNA group was significantly higher than that in PBS group (0.68±0.02, 0.63±0.08) and NC group (0.71±0.01, 0.66±0.10) (P<0.05), and the relative expression of anti-apoptosis protein bcl-2 decreased in siRNA group (0.38±0.02) than in PBS group (0.73±0.05) and NC group (0.69±0.06) (P<0.05). Conclusion: PLAUR promotes the activation of neutrophil-like cells and inhibits the apoptosis.

[The therapeutic effect and prognostic value of oligoclonal bands after autologous stem cell transplant in patients with multiple myeloma].

Objective: To investigate the therapeutic effect and prognostic value of oligoclonal bands (OB) in multiple myeloma (MM) patients after autologous stem cell transplant (ASCT). Methods: The data of 156 patients with MM who underwent ASCT after inductive treatment in the Department of Hematology, Jiangsu Provincial People's Hospital from December 2013 to February 2022 were retrospectively analyzed, including 91 males and 65 females. The median age was 56 (26, 71) years. Patients were divided into two groups according to OB formation after ASCT treatment, including OB group (n=60) and non-OB group (n=96). The last follow-up date was August 31, 2023, and the follow-up period was 42 (18, 117) months. The clinical baseline characteristics and efficacy of the two groups were compared. Progression-free survival (PFS) and overall survival (OS) were compared between the two groups by Kaplan-Meier method. Cox risk regression modal was used to analyze the risk factors associated with prognosis. Results: There were no significant differences in age, type, stage, risk stratification, extramedullary disease (EMD), proportion of circulating plasma cells and induction therapy regimen between OB and non-OB groups (all P>0.05). The proportion of patients in OB group who achieved complete response (CR) or above after ASCT treatment was 93.3% (56/60), which was higher than that in non-OB group (80.2%, 77/96) (P=0.024). The negative rate of minimal residual disease (MRD) in OB group was 66.7% (40/60), which was higher than that in non-OB group (34.4%, 33/96) (P=0.001). The median PFS and OS in the OB group were not reached, and the median PFS and OS in the non-OB group were 28 (2, 80) months and 86 (2, 100) months, respectively. The PFS (P<0.001) and OS (P=0.017) of patients with OB were considerably longer. In the Cox multivariate analysis, OB was an independent prognostic factor for PFS in MM patients (HR=0.314, 95%CI: 0.153-0.644, P=0.002). Subgroup analysis showed that among high-risk patients with mSMART, the OS of patients in OB group was not reached, which was significantly better than that of non-OB group [71 (2, 90) months, P=0.046]. However, no significant difference was observed in the OS of patients with OB and those with non-OB in standard risk group (not reached vs not reached, P=0.103). In those with EMD at diagnosis, patients with OB had significantly better OS than those with non-OB [not reached vs 47 (6, 74) months, P=0.037]. However, no significant difference was observed in the OS of patients with OB and those with non-OB in those without EMD at diagnosis [not reached vs 86 (2, 100) months, P=0.130]. Conclusions: OB formation after ASCT treatment in MM patients is related to the efficacy and prognosis. OB formation can increase the negative MRD rate, prolong the OS and improve the prognosis, especially for newly diagnosed patients with extramedullary disease or patients with high-risk genetic characteristics.

[The characteristics and impact on prognosis of cytopenia after anti-BCMA-CAR-T therapy in patients with relapsed and refractory multiple myeloma].

Objective: To investigate the characteristics of cytopenia and its impact on prognosis in patients with relapsed and refractory multiple myeloma (RRMM) after B-cell maturation antigen (BCMA) chimeric antigen receptor T-cell (CAR-T) immunotherapy therapy. Methods: Clinical data of 36 RRMM patients received BCMA CAR-T therapy at the First Affiliated Hospital of Nanjing Medical University from April 2017 to March 2023 were retrospectively collected. Among them, there were 17 males and 19 females, with an age [M (Q1, Q3)] of 62 (53, 67) years. The follow-up deadline was August 31, 2023, and the follow-up time [M (Q1, Q3)] was 33 (10, 30) months. The characteristics of cytopenia at different time points before lymphodepleting chemotherapy and after CAR-T cell infusion in all patients were analyzed. Kaplan-Meier method was used to compare the differences in progression-free survival (PFS) and overall survival (OS) in patients with different clinical characteristics. Single-cell sequencing analysis was used to analyze the changes in hematopoietic stem cells in three patients after CAR-T cell therapy. Results: The incidence of cytopenia after BCMA CAR-T cell therapy in 36 RRMM patients reached 100%. The incidence of neutropenia peaked on the 7th and 28th day after cell infusion with a biphasic pattern of change.Patients with all grade neutropenia reached 61.1% (22/36) and grade 3 or higher reached 33.3% (12/36) on the 7th day, while patients with all grade neutropenia reached 67.9% (19/28) and grade 3 or higher reached 28.6% (8/28) on the 28th day (P<0.001),respectively. The occurrence rate of lymphopenia reached a peak on the day of CAR-T cell infusion [97.2% (35/36) patients showed lymphopenia, while 80.6% (29/36) patients showed grade 3 or higher lymphopenia] (P<0.001).The incidence of all grade of thrombocytopenia and severe thrombocytopenia (grade 3 or higher) peaked on the 14th day after cell infusion, with the rates of 69.4% (25/36) and 30.6% (11/36) respectively, which had a prolonged duration(P<0.001). Even after 12 months, 40% (8/20) of patients still experienced thrombocytopenia.The incidence of anemia peaked on the 7th and 14th day after cell infusion, with a rate of 100% (36/36) (P<0.001). 50% (10/20) of patients still had anemia even 12 months after cell infusion. Kaplan-Meier survival analysis showed that patients with thrombocytopenia < grade 3 had undefined OS, while patients with thrombocytopenia ≥grade 3 had shorter OS [17 (95%CI: 2-32) months, χ2=4.154, P=0.042], indicating a poorer prognosis. However, there was no statistically significant difference in the relationship between other cytopenia and survival (all P>0.05). Single-cell sequencing analysis of bone marrow cells revealed decreased proliferation, increased apoptosis, and cell cycle arrest of hematopoietic stem cells after CAR-T cell infusion. Conclusions: All patients experienced varying degrees of cytopenia after receiving BCMA CAR-T cell infusion, and patients with thrombocytopenia ≥grade 3 had shorter OS and poorer prognosis.

Molecular Ionization Dissociation Induced by Interatomic Coulombic Decay in an ArCH_{4}-Electron Collision System.

Interatomic Coulombic decay (ICD) is a significant fragmentation mechanism observed in weakly bound systems. It has been widely accepted that ICD-induced molecular fragmentation occurs through a two-step process, involving ICD as the first step and dissociative-electron attachment (DEA) as the second step. In this study, we conducted a fragmentation experiment of ArCH_{4} by electron impact, utilizing the coincident detection of one electron and two ions. In addition to the well-known decay pathway that induces pure ionization of CH_{4}, we observed a new channel where ICD triggers the ionization dissociation of CH_{4}, resulting in the cleavage of the C-H bond and the formation of the CH_{3}^{+} and H ion pair. The high efficiency of this channel, as indicated by the relative yield of the Ar^{+}/CH_{3}^{+} ion pair, agrees with the theoretical prediction [L. S. Cederbaum, J. Phys. Chem. Lett. 11, 8964 (2020).JPCLCD1948-718510.1021/acs.jpclett.0c02259; Y. C. Chiang et al., Phys. Rev. A 100, 052701 (2019).PLRAAN2469-992610.1103/PhysRevA.100.052701]. These results suggest that ICD can directly break covalent bonds with high efficiency, bypassing the need for DEA. This finding introduces a novel approach to enhance the fragmentation efficiency of molecules containing covalent bonds, such as DNA backbone.

Brown goat yogurt: Metabolomics, peptidomics, and sensory changes during production.

Brown goat milk products have gained popularity for their unique taste and flavor. The emergence of chain-reversal phenomenon makes the design and development of goat milk products gradually tend to a consumer-oriented model. However, the precise mechanism of how browning and fermentation process causes characteristics is not clear. In an effort to understand how the treatments potentially lead to certain metabolite profile changes in goat milk, comprehensive, quantitative metabolomics and peptidomics analysis of goat milk samples after browning and fermentation were undertaken. An intelligent hybrid z-score standardization-principal components algorithm-multimodal denoizing autoencoder was used for feature fusion and hidden layer fusion in high-dimensional variable space. The fermentation process significantly improved the flavor of brown goat yogurt through the tricarboxylic acid-urea-glycolysis composite pathway. Bitter peptides HPFLEWAR, PPGLPDKY, and PPPPPKK have strong interactions with both putative dipeptidyl peptidase IV and angiotensin-converting enzyme, proving that brown goat yogurt can be considered as effective provider of potential putative dipeptidyl peptidase IV and angiotensin-converting enzyme inhibitors. The level of health-promoting bioactive components and sensory contributed to consumer selection. The proposed multimodal data integrative analysis platform was applicable to explain the effect of the dynamic changes of metabolites and peptides on consumer preferences.

Predictors and moderators of the response of adults with intellectual disabilities and depression to behavioural activation and guided self-help therapies.

BACKGROUND: No previous studies have reported predictors and moderators of outcome of psychological therapies for depression experienced by adults with intellectual disabilities (IDs). We investigated baseline variables as outcome predictors and moderators based on a randomised controlled trial where behavioural activation was compared with guided self-help. METHODS: This study was an exploratory secondary data analysis of data collected during a randomised clinical trial. Participants (n = 161) were randomised to behavioural activation or guided self-help and followed up for 12 months. Pre-treatment variables were included if they have previously been shown to be associated with an increased risk of having depression in adults with IDs or have been reported as a potential predictor or moderator of outcome of treatment for depression with psychological therapies. The primary outcome measure, the Glasgow Depression Scale for Adults with Learning Disabilities (GDS-LD), was used as the dependant variable in mixed effects regression analyses testing for predictors and moderators of outcome, with baseline GDS-LD, treatment group, study centre and antidepressant use as fixed effects, and therapist as a random effect. RESULTS: Higher baseline anxiety (mean difference in outcome associated with a 1 point increase in anxiety 0.164, 95% confidence interval [CI] 0.031, 0.297; P = 0.016), lower performance intelligence quotient (IQ) (mean difference in outcome associated with a 1 point increase in IQ 0.145, 95% CI 0.009, 0.280; P = 0.037) and hearing impairment (mean difference 3.449, 95% CI 0.466, 6.432; P = 0.024) were predictors of poorer outcomes, whilst greater severity of depressive symptoms at baseline (mean difference in outcome associated with 1 point increase in depression -0.160, 95% CI -0.806, -0.414; P < 0.001), higher expectation of change (mean difference in outcome associated with a 1 point increase in expectation of change -1.013, 95% CI -1.711, -0.314; p 0.005) and greater percentage of therapy sessions attended (mean difference in outcome with 1 point increase in percentage of sessions attended -0.058, 95% CI -0.099, -0.016; P = 0.007) were predictors of more positive outcomes for treatment after adjusting for randomised group allocation. The final model included severity of depressive and anxiety symptoms, lower WASI performance IQ subscale, hearing impairment, higher expectation of change and percentage of therapy sessions attended and explained 35.3% of the variance in the total GDS-LD score at 12 months (R2  = 0.353, F4, 128  = 17.24, P < 0.001). There is no evidence that baseline variables had a moderating effect on outcome for treatment with behavioural activation or guided self-help. CONCLUSIONS: Our results suggest that baseline variables may be useful predictors of outcomes of psychological therapies for adults with IDs. Further research is required to examine the value of these potential predictors. However, our findings suggest that therapists consider how baseline variables may enable them to tailor their therapeutic approach when using psychological therapies to treat depression experienced by adults with IDs.

Advice to remain active with arm pain reduces disability.

BACKGROUND: Arm pain is common amongst working-aged adults and causes substantial work disability. The results of a population-based randomized controlled trial (the ARM trial) suggested that advice to remain active reduced disability after 6 months. AIMS: To verify ARM trial results amongst people in paid employment. METHODS: The ARM trial recruited adults with distal arm pain referred for physiotherapy and randomized equally to three groups: wait-listed for physiotherapy (advised to rest); wait-listed for physiotherapy (advised to remain active) or early physiotherapy. The primary outcome was absence of disability at 26 weeks. Secondary analyses were undertaken amongst participants in paid employment. RESULTS: Amongst 538 trial participants, 347 (64%) were in paid employment, mean age 46.1 years and 47% in manual work. Employed participants were randomized equally to the three arms. Amongst the 271 (78% workers with 26-week data), 43% of those advised to remain active were free from disability, as compared with 37% of those advised to rest. Forty per cent of those who waited for physiotherapy were disability-free as compared with 35% of those treated rapidly. Advice to rest was associated with lower chances of recovery amongst workers who lift/carry weights and those who believed work had caused their symptoms (P = 0.023). CONCLUSIONS: Although not powered as a trial for workers only, our findings suggest that advising activity was as beneficial for people currently in paid work and may be superior to advice to rest in reducing disability. Addressing harmful beliefs about causation of symptoms has the potential to reduce disability.

Willingness to receive and recommend hypothetical mpox vaccination and associated factors in Chinese adults: a community-based survey in Shenzhen, China.

OBJECTIVES: China may face new threats to public health due to the increased risk of imported mpox (monkeypox) cases. However, research gaps exist in the acceptance of mpox vaccination and potential associated factors in the Chinese population. STUDY DESIGN: We conducted a cross-sectional study targeting community residents in Shenzhen, China, from August 5 to September 7 2022. METHODS: A self-administered questionnaire was used to collect information about demographic and health characteristics, mpox-related perceptions, and attitudes towards mpox vaccination. Multivariable logistic regression models were applied to detect the factors associated with willingness to receive and recommend mpox vaccination. RESULTS: A total of 2293 community residents were included in the analyses (average age: 34.03, female: 72.6%). Among the participants, 76.9% were aware of mpox, 62.1% were aware of the global mpox outbreak, but only 53.6% had a high knowledge level of mpox. Males had a higher proportion of high knowledge (56.9% vs 52.3%, P＜0.05) and a lower proportion of high worry (30.2% vs 45.4%, P＜0.05) than females. Approximately 69.1% of the participants were willing to vaccinate against mpox, and 69.6% were willing to recommend mpox vaccination to people around them, in which no gender difference was found. The obstacle reported most among people hesitant to receive vaccination was concerning the safety and side-effects, whereas it changed to be concerning the suitability due to individual health differences among people hesitant to recommend mpox vaccines. Factors associated with the willingness to receive and recommend mpox vaccination included having a history of influenza vaccination, having a history of COVID-19 vaccination, being aware of the global mpox outbreak, having a high knowledge level of mpox, and having a high level of mpox-related worry. CONCLUSIONS: This study identified a moderate willingness to receive and recommend mpox vaccination among Chinese adults. Without gender differences, willingness to receive and recommend mpox vaccination was significantly associated with mpox-related perceptions, such as awareness, knowledge, and worry. Authoritative and up-to-date information is needed to help the general population improve public confidence in mpox vaccines in China.

Effects of testis testosterone deficiency on gene expression in the adrenal gland and skeletal muscle of ducks.

1. Testosterone has an anabolic effect on skeletal muscle. The testes produce most of the testosterone in vivo, while the adrenal glands contribute smaller amounts. When testis testosterone is deficient the adrenal gland increases steroid hormone synthesis, which is referred to as compensatory testicular adaptation (CTA).2. To reveal the effects of testis testosterone deficiency on adrenal steroid hormones synthesis and skeletal muscle development, gene expression related to adrenal steroid hormones synthesis and skeletal muscle development were determined by RNA-seq.3. The results showed that castrating male ducks had significant effects on their body weight but no significant impact on cross-sectional area (CSA) or density of pectoral muscle fibres. In skeletal muscle protein metabolism, expression levels of the catabolic gene atrogin1/MAFbx and the anabolic gene eEF2 were significantly higher, with concomitant increases after castration. The adrenal glands' alteration of the steroid hormone 11ß-hydroxylase (CYP11B1) was significantly lower following castration.4. Expression pattern analysis showed that the adrenal glands' glucocorticoid receptor (NR3C1/GR) had a potential regulatory relationship with the skeletal muscle-related genes (Pax7, mTOR, FBXO32, FOXO3, and FOXO4).5. The data showed that castration affected muscle protein metabolism, adrenal steroid and testosterone synthesis. In addition, it was speculated that, after castration, steroid hormones produced by the adrenal gland could have a compensatory effect, which might mediate the changes in skeletal muscle protein metabolism and development.

[Histogram analysis of based on two-dimensional ultrasound images to differentiate medullary thyroid carcinoma and thyroid adenoma].

Objective: To investigate the feasibility and value of histogram analysis based on two-dimensional gray-scale ultrasonography in the differential diagnosis of medullary thyroid carcinoma (MTC) and thyroid adenoma (TA). Methods: The preoperative ultrasound images of 86 newly diagnosed MTC patients and 100 TA patients treated in the Cancer Hospital of Chinese Academy of Medical Sciences from January 2015 to October 2021 were collected. Histograms were performed based on the regions of interest (ROIs) delineated manually by two radiologists, thereafter, mean, variance, skewness, kurtosis, percentiles (1st, 10th, 50th, 90th, 99th) were generated. The histogram parameters between the MTC group and the TA group were compared, and the independent predictors were screened by multivariate logistic regression analysis. Receiver operating characteristic (ROC) analysis was used to compare the individual diagnostic efficacy and joint diagnostic efficacy of independent predictors. Results: Multivariate regression analysis showed that mean, skewness, kurtosis and 50th percentile were independent factors. The skewness and kurtosis in the MTC group were significantly higher than those in the TA group, and the mean and 50th percentile were significantly lower than those in the TA group. The area under the individual ROC curve of mean, skewness, kurtosis and 50th percentile is 0.654-0.778. The area under the combined ROC curve is 0.826. Conclusion: Histogram analysis based on two-dimensional gray-scale ultrasonography is a promising tool to distinguish MTC from TA, in which the joint diagnosis value of mean, skewness, kurtosis and 50th percentile is the highest.

[The 501st case: elevated blood glucose, chronic pancreatitis, and post- pancreatoduodenectomy malnutrition].

A 50-year-old man with a 15-year history of elevated blood glucose and an approximately 2-year history of diarrhea was admitted to the Peking Union Medical College Hospital. The initial diagnosis was type 2 diabetes. After repeated pancreatitis and pancreatoduodenectomy, severe pancreatic endocrine and exocrine dysfunction including alternating high and low blood glucose and fat diarrhea occurred. Tests for type 1 diabetes-related antibodies were all negative, C-peptide levels were substantially reduced, fat-soluble vitamin levels were reduced, and there was no obvious insulin resistance. Therefore, a diagnosis of pancreatic diabetes was clear. The patient was given small doses of insulin and supplementary pancreatin and micronutrients. Diarrhea was relieved and blood glucose was controlled. The purpose of this article is to raise clinicians' awareness of the possibility of pancreatic diabetes after pancreatitis or pancreatic surgery. Timely intervention and monitoring may reduce the occurrence of complications.

[Safety and effectiveness of Neuroform Atlas stent-assisted coiling in the endovascular treatment of intracranial aneurysms: a single-center observational study].

Objective: To investigate the safety and effectiveness of Neuroform Atlas stent-assisted coiling in the endovascular treatment of intracranial aneurysms. Methods: This was a retrospective, single-center observational study of 77 patients who underwent endovascular treatment of intracranial aneurysms using the Neuroform Atlas device at the Department of Neurology, People's Liberation Army General Hospital from July 2020 to May 2022. There were 34 males and 43 females, with a median (range) age of 59 (23-81) years. The degree and effect of aneurysm embolization were evaluated by modified Raymond grading post procedure and after 6 months. Complications occurring during the perioperative period were recorded. Vaso computed tomography was performed immediately after the operation to assess stent opening and adherence. Digital subtraction angiography was performed 6 months after discharge and the aneurysm was classified as cured, stable, or recurrent. Results: A total of 87 Atlases were successfully released in 77 cases. Angiography performed immediately after the embolization revealed 19 (24.7%) modified Raymond grade Ⅰ, 10 (13.0%) grade Ⅱ, and 48 (62.3%) grade Ⅲa cases. Three perioperative complications were observed including thrombotic events in 2 cases and stent migration in 1 case. A follow-up angiogram was available for 47 aneurysms, and showed that modified Raymond grade Ⅰ occlusion was achieved in 38 (80.9%) cases, grade Ⅱ in 2 (4.3%) cases, and grade Ⅲa in 7 (14.9%) cases. At the 6-month follow-up, 38 patients were cured and 7 were stable, whereas 2 patients experienced a recurrence of aneurysm. Stenosis of the parent artery occurred in 3 (6.4%) cases, including 2 at the head and 1 inside the stent. Conclusions: The results of this preliminary study suggest that Neuroform Atlas stent-assisted coiling has a high occlusion rate and low incidence of complications in the endovascular treatment of aneurysms. However, the effectiveness of this procedure for large aneurysms and long-term outcomes require further investigation.