Predicting balloon shape in percutaneous microcompression : an observational comparative analysis of Meckel's cave imaging and balloon morphology.

Achieving a pear-shaped balloon holds pivotal significance in the context of successful percutaneous microcompression procedures for trigeminal neuralgia. However, inflated balloons may assume various configurations, whether it is inserted into Meckel's cave or not. The absence of an objective evaluation metric has become apparent. To investigate the relationship between the morphology of Meckel's Cave and the balloon used in percutaneous microcompression for trigeminal neuralgia and establish objective criteria for assessing balloon shape in percutaneous microcompression procedures. This retrospective study included 58 consecutive patients with primary trigeminal neuralgia. Data included demographic, clinical outcomes, and morphological features of Meckel's cave and the balloon obtained from MRI and Dyna-CT imaging. MRI of Meckel's cave and Dyna-CT of intraoperative balloon were modeled, and the morphological characteristics and correlation were analyzed. The reconstructed balloon presented a fuller morphology expanding outward and upward on the basis of Meckel's cave. The projected area of balloon was strongly positively correlated with the projected area of Meckel's cave. The Pearson correlation coefficients were 0.812 (P<0.001) for axial view, 0.898 (P<0.001) for sagittal view and 0.813 (P<0.001) for coronal view. Similarity analysis showed that the sagittal projection image of Meckel's cave and that of the balloon had good similarity. This study reveals that the balloon in percutaneous microcompression essentially represents an expanded morphology of Meckel's cave, extending outward and upward. There is a strong positive correlation between the volume and projected area of the balloon and that of Meckel's cave. Notably, the sagittal projection image of Meckel's cave serves as a reliable predictor of the intraoperative balloon shape. This method has a certain generalizability and can help providing objective criteria for judging balloon shape during percutaneous microcompression procedures.

Development and validation of a multi-modality fusion deep learning model for differentiating glioblastoma from solitary brain metastases. / åŒºåˆ†èƒ¶è´¨æ¯ç»†èƒžç˜¤å’Œå•å‘æ€§è„‘è½¬ç§»ç˜¤çš„å¤šæ¨¡æ€èžåˆæ·±åº¦å­¦ä¹ æ¨¡åž‹çš„å¼€å‘å’ŒéªŒè¯.

OBJECTIVES: Glioblastoma (GBM) and brain metastases (BMs) are the two most common malignant brain tumors in adults. Magnetic resonance imaging (MRI) is a commonly used method for screening and evaluating the prognosis of brain tumors, but the specificity and sensitivity of conventional MRI sequences in differential diagnosis of GBM and BMs are limited. In recent years, deep neural network has shown great potential in the realization of diagnostic classification and the establishment of clinical decision support system. This study aims to apply the radiomics features extracted by deep learning techniques to explore the feasibility of accurate preoperative classification for newly diagnosed GBM and solitary brain metastases (SBMs), and to further explore the impact of multimodality data fusion on classification tasks. METHODS: Standard protocol cranial MRI sequence data from 135 newly diagnosed GBM patients and 73 patients with SBMs confirmed by histopathologic or clinical diagnosis were retrospectively analyzed. First, structural T1-weight, T1C-weight, and T2-weight were selected as 3 inputs to the entire model, regions of interest (ROIs) were manually delineated on the registered three modal MR images, and multimodality radiomics features were obtained, dimensions were reduced using a random forest (RF)-based feature selection method, and the importance of each feature was further analyzed. Secondly, we used the method of contrast disentangled to find the shared features and complementary features between different modal features. Finally, the response of each sample to GBM and SBMs was predicted by fusing 2 features from different modalities. RESULTS: The radiomics features using machine learning and the multi-modal fusion method had a good discriminatory ability for GBM and SBMs. Furthermore, compared with single-modal data, the multimodal fusion models using machine learning algorithms such as support vector machine (SVM), Logistic regression, RF, adaptive boosting (AdaBoost), and gradient boosting decision tree (GBDT) achieved significant improvements, with area under the curve (AUC) values of 0.974, 0.978, 0.943, 0.938, and 0.947, respectively; our comparative disentangled multi-modal MR fusion method performs well, and the results of AUC, accuracy (ACC), sensitivity (SEN) and specificity(SPE) in the test set were 0.985, 0.984, 0.900, and 0.990, respectively. Compared with other multi-modal fusion methods, AUC, ACC, and SEN in this study all achieved the best performance. In the ablation experiment to verify the effects of each module component in this study, AUC, ACC, and SEN increased by 1.6%, 10.9% and 15.0%, respectively after 3 loss functions were used simultaneously. CONCLUSIONS: A deep learning-based contrast disentangled multi-modal MR radiomics feature fusion technique helps to improve GBM and SBMs classification accuracy.

Application, knowledge and training needs regarding comprehensive geriatric assessment among geriatric practitioners in healthcare institutions: a cross-sectional study.

BACKGROUND: This study aimed to investigate the actual application, knowledge, and training needs of comprehensive geriatric assessment (CGA) among geriatric practitioners in China. METHODS: A total of 225 geriatric practitioners attending the geriatric medicine or geriatric nursing training were recruited for this cross-sectional study. The questionnaire included demographics, healthcare institution characteristics, the actual application, knowledge, training needs, and barriers to CGA and geriatric syndromes (GS). RESULTS: Physicians and nurses were 57.3% and 42.7%, respectively. 71.1% were female, with a median age was 35 years. Almost two-thirds (140/225) of geriatric practitioners reported exposure to CGA in their clinical practice. The top five CGA evaluation items currently used were malnutrition risk (49.8%), fall risk (49.8%), activity of daily living (48.0%), pain (44.4%), and cognitive function (42.7%). Median knowledge scores for the management procedures of GS ranged from 2 to 6. Physicians identified medical insurance payment issues (29.5%) and a lack of systematic specialist knowledge and technology (21.7%) as the two biggest barriers to practicing geriatrics. Nurses cited a lack of systematic specialist knowledge and technology (52.1%) as the primary barrier. In addition, physicians and nurses exhibited significant differences in their knowledge of CGA-specific evaluation items and management procedures for GS (all P < 0.05). However, there were no significant differences in their training needs, except for polypharmacy. CONCLUSIONS: The rate of CGA application at the individual level, as well as the overall knowledge among geriatric practitioners, was not adequate. Geriatric education and continuous training should be tailored to address the specific roles of physicians and nurses, as well as the practical knowledge reserves, barriers, and training needs they face.

Dynamics changes in metabolites and pancreatic lipase inhibitory ability of instant dark tea during liquid-state fermentation by Aspergillus niger.

Instant dark tea (IDT), prepared by liquid-state fermentation using Aspergillus niger, is known for its high theabrownins content and lipid-lowering effect. To explore the impact of fungal fermentation on IDT compositions and its pancreatic lipase inhibitory ability (PLIA), untargeted and targeted metabolomic analysis were applied to track the changes of metabolites over a 9-day fermentation period, and correlation analysis was then conducted between metabolites and PLIA of IDT. There were 54 differential metabolites exhibited significant changes from day 3 to day 5 of fermentation. The concentrations of theabrownins and caffeine increased during fermentation, while phenols and free amino acids decreased. The PLIA of IDT samples significantly increased from day 5 to day 9 of fermentation. Theabrownins not only positively correlated with the PLIA but also exhibited a high inhibition rate. These findings provide a theoretical basis to optimize the production of IDT as functional food ingredient.

Gas-Phase Alcoholysis of Benzylic Halides in the Atmospheric Pressure Ionization Source.

The present study investigates the gas-phase alcoholysis reaction of benzylic halides under atmospheric pressure chemical ionization (APCI) conditions. The APCI corona discharge is used to initiate the novel reaction, which is monitored by ion trap mass spectrometry (IT-MS). The model compound α,α,α-trifluorotoluene is applied to observe the cascade methoxylation reaction during the +APCI-MS analysis, resulting in the formation of [PhC(OCH3)2]+. Based on the results of isotopic labeling and substrate expansion experiments, an addition-elimination mechanism is proposed: initially, the reaction was initiated by the dissociation of fluorine from PhCF3 under APCI condition, leading to the formation of [PhCF2]+; subsequently, two methanol molecules nucleophilicly attack [PhCF2]+ stepwisely, accompanied by the elimination of HF, yielding the product ion [PhC(OCH3)2]+. The proposed mechanism was further corroborated by theoretical calculations. The results of substrate scope expansion experiments suggest that this in-source reaction has the potential to differentiate the positional isomers of alcohols and phenols.

Erratum: Targeting sphingosine kinase 2 suppresses cell growth and synergizes with BCL2/BCL-XL inhibitors through NOXA-mediated MCL1 degradation in cholangiocarcinoma.

[This corrects the article on p. 546 in vol. 9, PMID: 30949409.].

Exploring the neural mechanisms underlying achalasia: A study of functional connectivity and regional brain activity.

BACKGROUND AND AIMS: The pathophysiology of achalasia, which involves central nuclei abnormalities, remains unknown. We investigated the resting-state functional MRI (rs-fMRI) features of patients with achalasia. METHODS: We applied resting-state functional MRI (rs-fMRI) to investigate the brain features in patients with achalasia (n = 27), compared to healthy controls (n = 29). Focusing on three regions of interest (ROIs): the dorsal motor nucleus of the vagus (DMV), the nucleus ambiguus (NA), and the nucleus of the solitary tract (NTS), we analyzed variations in resting-state functional connectivity (rs-FC), fractional amplitude of low-frequency fluctuations (fALFF), and regional homogeneity (ReHo). RESULTS: Achalasia patients demonstrated stronger functional connectivity between the NA and the right precentral gyrus, left postcentral gyrus, and left insula. No significant changes were found in the DMV or NTS. The fMRI analysis showed higher rs-FC values for NA-DMV and NA-NTS connections in achalasia patients. Achalasia patients exhibited decreased fALFF values in the NA, DMV, and NTS regions, as well as increased ReHo values in the NA and DMV regions. A positive correlation was observed between fALFF values in all six ROIs and the width of the barium meal. The NTS fALFF value and NA ReHo value displayed a positive correlation with integrated relaxation pressure (IRP), while the ReHo value in the right precentral gyrus showed an inverse correlation with the height of the barium meal. CONCLUSIONS: Abnormal rs-FC and regional brain activity was found in patients with achalasia. Our study provides new insights into the pathophysiology of achalasia and highlights the potential of rs-fMRI in improving the diagnosis and treatment of this condition.

Sensomics-Assisted Characterization of Fungal-Flowery Aroma Components in Fermented Tea Using Eurotium cristatum.

Fermented tea (FT) using a single Eurotium cristatum strain can produce a pleasant fungal-flowery aroma, which is similar to the composite aroma characteristic of minty, flowery, and woody aromas, but its molecular basis is not yet clear. In this study, solvent-assisted flavor evaporation and gas chromatography-mass spectrometry/olfactometry were applied to isolate and identify volatiles from the FT by E. cristatum. The application of an aroma extract dilution analysis screened out 43 aroma-active compounds. Quantification revealed that there were 11 odorants with high odor threshold concentrations. Recombination and omission tests revealed that nonanal, methyl salicylate, decanoic acid, 4-methoxybenzaldehyde, α-terpineol, phenylacetaldehyde, and coumarin were the major odorants in the FT. Addition tests further verified that methyl salicylate, 4-methoxybenzaldehyde, and coumarin were the key odorants for fungal-flowery aroma, each corresponding to minty, woody, and flowery aromas, respectively. 4-Methoxybenzaldehyde and coumarin were newly found odorants for fungal-flowery aroma in FT, and 4-methoxybenzaldehyde had not been reported as a tea volatile compound before. This finding may guide future industrial production optimization of FT with improved flavor.

Lithium chloride induces apoptosis by activating endoplasmic reticulum stress in pancreatic cancer.

Lithium compounds, a classic class of metal complex medicine that target GSK 3ß and are widely known as mood-stabilizer, have recently been reported as potential anti-tumor drugs. The objective of this investigation was to explore the anticancer potential of lithium chloride (LiCl) and elucidate its mode of action in pancreatic cancer cells. The MTT, colony formation, and Edu assay were used to evaluate the impact of LiCl on pancreatic cancer cell proliferation. Various methods were employed to investigate the anti-tumor activity of LiCl and its underlying mechanisms. Cell cycle analysis and apoptosis detection assays were utilized for in vitro experiments, while the orthotopic pancreatic cancer mouse model was employed to evaluate the effectiveness of LiCl treatment in vivo. Furthermore, the impact of LiCl on the proliferation of patient-derived organoids was also studied. The results demonstrated that LiCl inhibited the proliferation of pancreatic cancer (PC) cells, induced G2/M phase arrest, and activated apoptosis. Notably, the triggering of endoplasmic reticulum (ER) stress by LiCl was observed, leading to the activation of the PERK/CHOP/GADD34 pathway, which subsequently promoted apoptosis in PC cells. In the future, Lithium compounds could become an essential adjunct in the treatment of human pancreatic cancer.

Associations of intrinsic capacity, fall risk and frailty in old inpatients.

Introduction: This study explored the associations of intrinsic capacity (IC), fall risk, and frailty in geriatric inpatients. Methods: A total of 703 hospitalized patients aged 75 years or older were recruited for this retrospective observational study from Zhejiang Hospital using a comprehensive geriatric assessment. The IC composite score was constructed from the scores of the Chinese version of the Mini-Mental State Examination, Short Physical Performance Battery, Short Form Mini Nutritional Assessment, 15-item Geriatric Depression Scale, and self-reported hearing and vision impairment. Adverse outcomes were recorded as the fall risk and frailty using the Morse Fall Scale and the Clinical Frailty Scale. Spearman's correlation coefficient analyses and multivariate logistic regression models were used to explore the associations between IC, high fall risk, and frailty. Results: Declined IC composite scores were associated with increased risks of falls [odds ratio (OR) = 0.64, 95% confidence interval (CI): 0.57-0.72] and frailty (OR = 0.45, 95%CI: 0.37-0.54) among older hospitalized patients after adjusting for the related potential confounders. In addition, decreased cognitive, vitality, locomotion, and psychological scores were associated with increased adverse health conditions, with ORs ranging from 0.26 to 0.70. Vision impairment was observed to increase the risk of frailty (OR = 0.42, 95%CI: 0.23-0.76) after adjusting for the related potential confounders. Discussion: This study indicated that declined IC was associated with fall risk and frailty in older inpatients. Further prospective studies are needed to explore the longitudinal associations between baseline IC and subsequent risk of falls and frailty.

An ECG Signal Acquisition and Analysis System Based on Machine Learning with Model Fusion.

Recently, cardiovascular disease has become the leading cause of death worldwide. Abnormal heart rate signals are an important indicator of cardiovascular disease. At present, the ECG signal acquisition instruments on the market are not portable and manual analysis is applied in data processing, which cannot address the above problems. To solve these problems, this study proposes an ECG acquisition and analysis system based on machine learning. The ECG analysis system responsible for ECG signal classification includes two parts: data preprocessing and machine learning models. Multiple types of models were built for overall classification, and model fusion was conducted. Firstly, traditional models such as logistic regression, support vector machines, and XGBoost were employed, along with feature engineering that primarily included morphological features and wavelet coefficient features. Subsequently, deep learning models, including convolutional neural networks and long short-term memory networks, were introduced and utilized for model fusion classification. The system's classification accuracy for ECG signals reached 99.13%. Future work will focus on optimizing the model and developing a more portable instrument that can be utilized in the field.

Single cell transcriptomic analyses implicate an immunosuppressive tumor microenvironment in pancreatic cancer liver metastasis.

Pancreatic ductal adenocarcinoma (PDAC) is a highly metastatic disease refractory to all targeted and immune therapies. However, our understanding of PDAC microenvironment especially the metastatic microenvironment is very limited partly due to the inaccessibility to metastatic tumor tissues. Here, we present the single-cell transcriptomic landscape of synchronously resected PDAC primary tumors and matched liver metastases. We perform comparative analysis on both cellular composition and functional phenotype between primary and metastatic tumors. Tumor cells exhibit distinct transcriptomic profile in liver metastasis with clearly defined evolutionary routes from cancer cells in primary tumor. We also identify specific subtypes of stromal and immune cells critical to the formation of the pro-tumor microenvironment in metastatic lesions, including RGS5+ cancer-associated fibroblasts, CCL18+ lipid-associated macrophages, S100A8+ neutrophils and FOXP3+ regulatory T cells. Cellular interactome analysis further reveals that the lack of tumor-immune cell interaction in metastatic tissues contributes to the formation of the immunosuppressive microenvironment. Our study provides a comprehensive characterization of the transcriptional landscape of PDAC liver metastasis.

A protocol for randomized controlled trial on multidisciplinary interventions for mobility limitation in the older adults (M-MobiLE).

BACKGROUND: Mobility limitation-the loss of exercise capacity or independent living ability-is a common geriatric syndrome in older adults. As a potentially reversible precursor to disability, mobility limitation is influenced by various factors. Moreover, its complex physiological mechanism hinders good therapeutic outcomes with a single-factor intervention. Most hospitals have not incorporated the diagnosis and evaluation of mobility limitation into medical routines nor developed a multidisciplinary team (MDT) treatment plan. We aim to conduct a clinical trial titled "A Multidisciplinary-team approach for management of Mobility Limitation in Elderly (M-MobiLE)" to explore the effect of the MDT decision-making intervention for mobility limitation. METHODS: The M-MobiLE study will be a multicenter, randomized, and controlled trial. We will recruit a minimum of 66 older inpatients with mobility limitation from at least five hospitals. Older patients with mobility limitation admitted to the geriatrics department will be included. Short-Physical Performance Battery (SPPB), Activities of Daily Living (ADL), Function Impairment Screening Tool (FIST), Geriatric Depression Scale (GDS-15), Short Form - 12 (SF-12), Fried frailty phenotype, social frailty, Morse Fall Risk Scale, SARC-CalF, Mini-Mental State Examination (MMSE), Mini-Nutritional Assessment Short-Form (MNA-SF), and intrinsic capacity will be assessed. The intervention group will receive an exercise-centered individualized MDT treatment, including exercise, educational, nutritional, medical, and comorbidity interventions; the control group will receive standard medical treatment. The primary outcome is the change in the SPPB score, and the secondary outcomes include increased SF-12, ADL, FIST, MMSE, MNA-SF, and intrinsic capacity scores and decreased GDS-15 and SARC-CalF scores. CONCLUSION: Our results will help develop a multidisciplinary decision-making clinical pathway for inpatients with mobility limitation, which can be used to identify patients with mobility limitation more effectively, improve mobility, and reduce the risk of falls, frailty, and death in older inpatients. The implementation of this MDT strategy may standardize the treatment of mobility limitation, reduce adverse prognosis, and improve quality of life. TRIAL REGISTRATION: ChiCTR, ChiCTR2200056756, Registered 19 February 2022.

Effect of the Dual Glucose­Dependent Insulinotropic Peptide/Gulcagon­like Peptide 1 Receptor Agonist Tirzepatide on Lipid Profile and Waist Circumference: A Systematic Review and Meta­analysis

PURPOSE: Tirzepatide, a dual glucose-dependent insulinotropic peptide and glucagon-like peptide 1 receptor agonist, has been approved by the US Food and Drug Administration for the treatment of type 2 diabetes. The purpose of this meta-analysis is to evaluate the impact of tirzepatide on lipid profile and waist circumference (WC), both of which are risk factors of cardiovascular diseases. METHODS: The PubMed, Embase, Cochrane Library, Web of Science, and ClinicalTrials.gov databases were systematically searched for articles published from database inception to July 31, 2022. This meta-analysis included 7 randomized controlled trials with a minimum duration of 12 weeks that compared tirzepatide with placebo or other antidiabetic medications. The random-effects model was used to estimate mean differences in lipid profile and WC from baseline. The Cochrane risk-of-bias tool for randomized trials, version 2 was used to assess the outcome's risk of bias. We evaluated the evidence using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) system. FINDINGS: A total of 8 articles from 7 trials with 7151 participants were included. All 3 eligible maintenance doses of tirzepatide (5, 10, and 15 mg once a week) were effective in increasing total cholesterol (TC) (P < 0.05), HDL-C (P < 0.05), VLDL-C (P < 0.01), triglyceride (TG) (P < 0.01), and WC (P < 0.01) changes from baseline compared with control agents including placebo, semaglutide, dulaglutide, and degludec. Although the evidence for VLDL-C and TGs by GRADE were high or moderate, the evidences for TC, HDL-C, and WC were low or moderate. Only 5mg once-weekly tirzepatide (P < 0.05), not 10 or 15 mg, could induce significant alteration in LDL-C before sensitivity analysis. The evidence by GRADE was moderate. IMPLICATIONS: Tirzepatide had superiority over placebo or other antidiabetic agents in controlling lipid and WC levels. However, the levels of evidence by GRADE varied greatly across different outcome indicators. Limitations of the study include evaluating secondary outcomes of original trials for the meta-analyses, not assessing the effect of baseline lipid-lowering therapy on lipid levels, and not exploring the bias induced by glycemic improvement and weight loss.

Recombinant Antimicrobial Peptide OaBac5mini Alleviates Inflammation in Pullorum Disease Chicks by Modulating TLR4/MyD88/NF-κB Pathway.

Pullorum disease (PD), caused by Salmonella Pullorum (S. Pullorum), is a serious threat to the poultry industry worldwide. Antimicrobial peptides (AMPs) have drawn extensive attention as new-generation antibiotics because of their broad antimicrobial spectrum, low resistance, and low cytotoxicity. AMP OaBac5mini exhibits strong antibacterial activity against Gram-negative bacteria, but its efficacy and anti-inflammatory effects on chicks with PD remain unclear. The aim of this study was to generate recombinant OaBac5mini via the Escherichia coli (E. coli) recombinant expression system and evaluate its antibacterial effect against S. Pullorum in vitro and in vivo. Real-time cellular analysis (RTCA) results showed that recombinant OaBac5mini exhibited no cytotoxicity on IPEC-J2 and RAW 264.7 cells and significantly alleviated the drop in the cell index of S. Pullorum-infected cells (p < 0.0001). In the chick model of PD, recombinant OaBac5mini significantly attenuated the increase in organ indexes (heart, liver, spleen, and kidney) and bacterial loads (liver and spleen) induced by S. Pullorum. Histopathology examination showed that recombinant OaBac5mini ameliorated histopathological changes and inflammation in chicks with PD, including impaired epithelium of duodenal villi, infiltration of pseudoacidophilic granulocytes in the cecum and bursa of Fabricius, congested blood clots and increased macrophages in the liver, and increased lymphoid nodule and B lymphocytes in the spleen. Western blot and quantitative real-time PCR (qRT-PCR) results indicated that recombinant OaBac5mini alleviated inflammation by modulating innate immunity through the TLR4/MyD88/NF-κB pathway and by suppressing the expression of pro-inflammatory cytokines. These results suggested that recombinant OaBac5mini has good potential as a clinical substitute for antibiotics in PD intervention.

Protein tyrosine phosphatase nonreceptor type 2 exerts antimetastatic functions in pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is a highly invasive tumor with a dismal prognosis. Recent studies have demonstrated PTPN2 (protein tyrosine phosphatase nonreceptor type 2) as a potential target for cancer therapy. However, the functions of PTPN2 in PDAC progression remain poorly understood. In this study, we found PTPN2 expression was downregulated in PDAC tissues, and decreased PTPN2 expression was associated with unfavorable prognosis. Functional studies indicated that PTPN2 knockdown promoted the migration and invasion abilities of PDAC cells in vitro, and the liver metastasis in vivo through epithelial-mesenchymal transition process. Mechanistically, MMP-1 was identified as a downstream target of PTPN2 via RNA-seq data and was responsible for the enhanced metastasis of PDAC cells upon PTPN2 knockdown. Moreover, according to chromatin immunoprecipitation and electrophoretic mobility shift assay, PTPN2 depletion transcriptionally activated MMP-1 via regulating the interaction of p-STAT3 with its distal promoter. This study, for the first time, demonstrated that PTPN2 inhibited PDAC metastasis, and presented a novel PTPN2/p-STAT3/MMP-1 axis in PDAC progression.

Revelation of volatile contributions in green teas with different aroma types by GC-MS and GC-IMS.

Aroma types of green teas associate with their commercial prices and consumer acceptance, mainly including floral-like (HX), chestnut-like (LX), and fresh (QX) aromas. However, the volatile differences and specificities in these aroma types are still unclear. Herein, Taiping Houkui green teas with HX, LX, and QX aromas were processed separately with the same fresh tea leaves. Ninety-four and seventy-eight volatiles were detected and identified by headspace solid-phase microextraction gas chromatography-mass spectrometry (HS-SPME-GC-MS) and headspace gas chromatography-ion mobility spectrometry (HS-GC-IMS), respectively. Candidate differential volatiles among the tea samples were determined by the variable importance in projection (VIP) of the partial least squares-discriminant analysis (PLS-DA) and were further confirmed by the relative odor activity value (ROAV) and odor description. The volatiles 1-hexanol, linalool oxide (furanoid), linalool, geraniol, (E)-ß-ionone, isoamyl acetate, and 2-methylpropanal enriched in HX and contributed to the floral-like aroma, while 3-methylbutanal, 2-ethyl-1-hexanol, indole, ß-damascone, and cedrol enriched in LX and contributed to the chestnut-like aroma. This study reveals the specificities and contributions of volatiles in green teas with different aromas, thus providing new insights into the molecular basis of different flavored teas, benefiting for their precision processing and targeted quality control.

PD-1 blockade plus chemoradiotherapy as preoperative therapy for patients with BRPC/LAPC: A biomolecular exploratory, phase II trial.

This is a phase II study of PD-1 blockade plus chemoradiotherapy as preoperative therapy for patients with locally advanced or borderline resectable pancreatic cancer (LAPC or BRPC, respectively). Twenty-nine patients are enrolled in the study. The objective response rate (ORR) is 60%, and the R0 resection rate is 90% (9/10). The 12-month progression-free survival (PFS) rate and 12-month overall survival (OS) rate are 64% and 72%, respectively. Grade 3 or higher adverse events are anemia (8%), thrombocytopenia (8%), and jaundice (8%). Circulating tumor DNA analysis reveals that patients with a >50% decline in maximal somatic variant allelic frequency (maxVAF) between the first clinical evaluation and baseline have a longer survival outcome and a higher response rate and surgical rate than those who are not. PD-1 blockade plus chemoradiotherapy as preoperative therapy displays promising antitumor activity, and multiomics potential predictive biomarkers are identified and warrant further verification.