The current infection with Helicobacter pylori and association with upper gastrointestinal lesions and risk of upper gastrointestinal cancer: Insights from multicenter population-based cohort study.

The relationship between Helicobacter pylori (H. pylori) infection and upper gastrointestinal (UGI) cancers is complex. This multicenter, population-based cohort study conducted in seven areas in China aimed to assess the correlation between current H. pylori infection and the severity of UGI lesions, as well as its association with the risk of gastric cancer (GC) and esophageal cancer (EC). From 2015 to 2017, 27,085 participants (aged 40-69) completed a standardized questionnaire, and underwent a 13C-urea breath test. Then a subset underwent UGI endoscopy to assess the UGI lesion detection rates. All individuals were followed up until December 2021 to calculate the hazard ratios (HRs) for UGI cancers. H. pylori infection prevalence was 45.9%, and among endoscopy participants, 22.2% had gastric lesions, 19.2% had esophageal lesions. Higher detection rates of gastric lesions were noted in the H. pylori-positive population across all lesion severity levels. Over a median follow-up of 6.3 years, 104 EC and 179 GC cases were observed, including 103 non-cardia gastric cancer (NCGC) cases and 76 cardia gastric cancer (CGC) cases. H. pylori-infected individuals exhibited a 1.78-fold increased risk of GC (HR 1.78, 95% confidence interval [CI] 1.32-2.40) but no significant increase in EC risk (HR 1.07, 95% CI 0.73-1.57). Notably, there was a higher risk for both NCGC and CGC in H. pylori-infected individuals. This population-based cohort study provides valuable evidence supporting the association between current H. pylori infection and the risk of both NCGC and CGC. These findings contribute to the empirical basis for risk stratification and recommendations for UGI cancer screening.

Comparative assessment of established and deep learning-based segmentation methods for hippocampal volume estimation in brain magnetic resonance imaging analysis.

In this study, our objective was to assess the performance of two deep learning-based hippocampal segmentation methods, SynthSeg and TigerBx, which are readily available to the public. We contrasted their performance with that of two established techniques, FreeSurfer-Aseg and FSL-FIRST, using three-dimensional T1-weighted MRI scans (n = 1447) procured from public databases. Our evaluation focused on the accuracy and reproducibility of these tools in estimating hippocampal volume. The findings suggest that both SynthSeg and TigerBx are on a par with Aseg and FIRST in terms of segmentation accuracy and reproducibility, but offer a significant advantage in processing speed, generating results in less than 1 min compared with several minutes to hours for the latter tools. In terms of Alzheimer's disease classification based on the hippocampal atrophy rate, SynthSeg and TigerBx exhibited superior performance. In conclusion, we evaluated the capabilities of two deep learning-based segmentation techniques. The results underscore their potential value in clinical and research environments, particularly when investigating neurological conditions associated with hippocampal structures.

Virtual MOLLI Target: Generative Adversarial Networks Toward Improved Motion Correction in MRI Myocardial T1 Mapping.

BACKGROUND: The modified Look-Locker inversion recovery (MOLLI) sequence is commonly used for myocardial T1 mapping. However, it acquires images with different inversion times, which causes difficulty in motion correction for respiratory-induced misregistration to a given target image. HYPOTHESIS: Using a generative adversarial network (GAN) to produce virtual MOLLI images with consistent heart positions can reduce respiratory-induced misregistration of MOLLI datasets. STUDY TYPE: Retrospective. POPULATION: 1071 MOLLI datasets from 392 human participants. FIELD STRENGTH/SEQUENCE: Modified Look-Locker inversion recovery sequence at 3 T. ASSESSMENT: A GAN model with a single inversion time image as input was trained to generate virtual MOLLI target (VMT) images at different inversion times which were subsequently used in an image registration algorithm. Four VMT models were investigated and the best performing model compared with the standard vendor-provided motion correction (MOCO) technique. STATISTICAL TESTS: The effectiveness of the motion correction technique was assessed using the fitting quality index (FQI), mutual information (MI), and Dice coefficients of motion-corrected images, plus subjective quality evaluation of T1 maps by three independent readers using Likert score. Wilcoxon signed-rank test with Bonferroni correction for multiple comparison. Significance levels were defined as P < 0.01 for highly significant differences and P < 0.05 for significant differences. RESULTS: The best performing VMT model with iterative registration demonstrated significantly better performance (FQI 0.88 ± 0.03, MI 1.78 ± 0.20, Dice 0.84 ± 0.23, quality score 2.26 ± 0.95) compared to other approaches, including the vendor-provided MOCO method (FQI 0.86 ± 0.04, MI 1.69 ± 0.25, Dice 0.80 ± 0.27, quality score 2.16 ± 1.01). DATA CONCLUSION: Our GAN model generating VMT images improved motion correction, which may assist reliable T1 mapping in the presence of respiratory motion. Its robust performance, even with considerable respiratory-induced heart displacements, may be beneficial for patients with difficulties in breath-holding. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY: Stage 1.

Preliminary assessment of portable sleep monitoring for diagnosis of obstructive sleep apnea in children.

OBJECTIVE: By observing the differences in sleep parameters between portable sleep monitoring (PM) and polysomnography (PSG) in children, we aimed to investigate the diagnostic value and feasibility of PM in children with suspected obstructive sleep apnea (OSA). STUDY DESIGN: This prospective study enrolled consecutive children (aged 3-14 years) with suspected OSA in Shenzhen Children's Hospital. They had PSG and PM in the sleep laboratory. Clinical parameters of the two sleep monitoring methods were compared. RESULTS: A total of 58 children participated. They were classified into two groups according to age: 28 children aged 3 to 5 years and 30 children aged 6 to 14 years. No significant differences were observed in apnea-hypopnea index (AHI), lowest oxygen saturation (LSaO2), and mean oxygen saturation (MSaO2) between PM and PSG, but the sleep efficiency with PM was significantly higher (3-5 years age: 92.2 ± 11.3% vs 85.2 ± 14.3%, 6-14 years age: 93.2 ± 14.5% vs 84.8 ± 16.3%, both P < 0.05) than the sleep efficiency with PSG. Pearson correlation analysis indicated a strong correlation between AHI, LSaO2, MSaO2, and sleep efficiency measured by PSG and PM. Receiver operating characteristic curve (ROC) analysis showed that PM was a reliable diagnostic tool for OSA. PM has high sensitivity (3-5 years age: 95.8%, 6-14 years age: 96.3%) and low specificity (3-5 years age: 25.0%, 6-14 years age: 33.3%) for OSA in children. Thus, there is a low rate of missed diagnoses, but there is some inaccuracy in excluding children who do not have OSA. CONCLUSION: The results showed that PM has a good correlation with the various parameters of PSG. PM may be a reliable tool for diagnosing moderate and severe OSA in children, especially those who cannot cooperate with PSG or who have limited access to PSG.

A study on pulmonary function in children with obstructive sleep apnea hypopnea syndrome.

OBJECTIVE: To investigate the pulmonary function of children with obstructive sleep apnea syndrome. METHODS: A total of 328 children aged 3 to 12 years old who were evaluated for a sleep disorder from January 2022 to June 2023 were selected as the observation group, classified into mild, moderate, and severe categories based on the apnea hypopnea index. The number of children with mild, moderate, and severe obstructive sleep apnea is 228, 62, and 28 respectively. Additionally, 126 healthy individuals aged 3 to 13 years old undergoing health examinations during the same period were selected as the control group. All subjects underwent sleep respiratory monitoring, pulmonary function tests, and impulse oscillometry. Comparative analysis was performed on pulmonary function indices (forced vital capacity, maximum ventilation, inspiratory capacity, total lung capacity, and inspiratory reserve volume), and respiratory impedance indices (resonant frequency, total respiratory impedance, viscous resistance at 5 Hz, 20 Hz, and 35 Hz). Pulmonary function indices were also compared among patients in the observation group with mild, moderate, and severe conditions. RESULTS: In the observation group, the FVC pre% of patients decreased by 10.5 ± 5.99 compared to the control group. The MVV of the control group decreased by 28.10 ± 2.22 compared to patients in the observation group. The IC of the control group decreased by 0.68 ± 0.44 compared to patients in the observation group. The TLC of the control group decreased by 1.354 ± 0.51 compared to patients in the observation group. The ERV of the control group decreased by 0.53 ± 0.30 compared to patients in the observation group. Additionally, the Fres, Zrs, R5, R20, and R35 of the observation group were higher than those of the control group by 10.73 ± 0.18, 1.78 ± 0.24, 0.11 ± 0.17, 0.86 ± 0.13, and 0.02 ± 0.21, respectively. In sum, the pulmonary function indices of the observation group were significantly lower than those of the control group, while the respiratory impedance indices were higher (P < 0.05). Within the observation group, the pulmonary function indices of severe patients were lower than those of moderate and mild patients, and moderate patients had lower pulmonary function indices than mild patients (P < 0.05). CONCLUSION: The pulmonary function of children with obstructive sleep apnea syndrome is impaired and varies in severity. There are significant differences in pulmonary function, underscoring the importance of monitoring pulmonary function in these children for clinical assessment and treatment prognosis.

Deriving a robust deep-learning model for subcortical brain segmentation by using a large-scale database: Preprocessing, reproducibility, and accuracy of volume estimation.

Increasing the accuracy and reproducibility of subcortical brain segmentation is advantageous in various related clinical applications. In this study, we derived a segmentation method based on a convolutional neural network (i.e., U-Net) and a large-scale database consisting of 7039 brain T1-weighted MRI data samples. We evaluated the method by using experiments focused on three distinct topics, namely, the necessity of preprocessing steps, cross-institutional and longitudinal reproducibility, and volumetric accuracy. The optimized model, MX_RW-where "MX" is a mix of RW and nonuniform intensity normalization data and "RW" is raw data with basic preprocessing-did not require time-consuming preprocessing steps, such as nonuniform intensity normalization or image registration, for brain MRI before segmentation. Cross-institutional testing revealed that MX_RW (Dice similarity coefficient: 0.809, coefficient of variation: 4.6%, and Pearson's correlation coefficient: 0.979) exhibited a performance comparable with that of FreeSurfer (Dice similarity coefficient: 0.798, coefficient of variation: 5.6%, and Pearson's correlation coefficient: 0.973). The computation time per dataset of MX_RW was generally less than 5 s (even when tested without graphics processing units), which was notably faster than FreeSurfer. Thus, for time-restricted applications, MX_RW represents a competitive alternative to FreeSurfer.

The role of input imaging combination and ADC threshold on segmentation of acute ischemic stroke lesion using U-Net.

BACKGROUND: To evaluate the effect of the weighting of input imaging combo and ADC threshold on the performance of the U-Net and to find an optimized input imaging combo and ADC threshold in segmenting acute ischemic stroke (AIS) lesion. METHODS: This study retrospectively enrolled a total of 212 patients having AIS. Four combos, including ADC-ADC-ADC (AAA), DWI-ADC-ADC (DAA), DWI-DWI-ADC (DDA), and DWI-DWI-DWI (DDD), were used as input images, respectively. Three ADC thresholds including 0.6, 0.8 and 1.8 × 10-3 mm2/s were applied. Dice similarity coefficient (DSC) was used to evaluate the segmentation performance of U-Nets. Nonparametric Kruskal-Wallis test with Tukey-Kramer post-hoc tests were used for comparison. A p < .05 was considered statistically significant. RESULTS: The DSC significantly varied among different combos of images and different ADC thresholds. Hybrid U-Nets outperformed uniform U-Nets at ADC thresholds of 0.6 × 10-3 mm2/s and 0.8 × 10-3 mm2/s (p < .001). The U-Net with imaging combo of DDD had segmentation performance similar to hybrid U-Nets at an ADC threshold of 1.8 × 10-3 mm2/s (p = .062 to 1). The U-Net using the imaging combo of DAA at the ADC threshold of 0.6 × 10-3 mm2/s achieved the highest DSC in the segmentation of AIS lesion. CONCLUSIONS: The segmentation performance of U-Net for AIS varies among the input imaging combos and ADC thresholds. The U-Net is optimized by choosing the imaging combo of DAA at an ADC threshold of 0.6 × 10-3 mm2/s in segmentating AIS lesion with highest DSC. KEY POINTS: • Segmentation performance of U-Net for AIS differs among input imaging combos. • Segmentation performance of U-Net for AIS differs among ADC thresholds. • U-Net is optimized using DAA with ADC = 0.6 × 10-3 mm2/s.

Effects of drug-induced sleep endoscopy in children with conventional obstructive sleep apnea-hypopnea syndrome: a systematic review and meta-analysis.

PURPOSE: This study aimed to conduct a meta-analysis and systematic review of drug-induced sleep endoscopy (DISE) in pediatric conventional obstructive sleep apnea-hypopnea syndrome (OSAHS) without previous upper airway surgery, or comorbidity, to evaluate the change in treatment strategies and to identify obstructive sites observed during DISE. This study aimed to explore the role of DISE in the management of pediatric conventional OSAHS. METHODS: A comprehensive search was conducted using both computerized and manual methods to retrieve relevant case studies on DISE-guided treatment of pediatric conventional OSAHS from databases including PubMed, EMBASE, Cochrane Library, Web of Science, CNKI, WF, and VIP database. The search period extended from database inception to January 2023. Strict inclusion and exclusion criteria were applied to select relevant literature, and data extraction was performed accordingly. Meta-analysis was conducted using the Stata 16.0 software. RESULTS: A total of 761 patients from four studies were included in the meta-analysis. All pediatric patients had no history of upper airway surgery, craniofacial abnormalities, or syndromes other than OSAHS. The quality assessment revealed that the included studies were of low methodological quality and consisted of non-randomized case studies. Meta-analysis results indicated that in pediatric patients with OSAHS, the obstruction rates observed during DISE were as follows: nasopharyngeal (adenoid) obstruction 93%, soft palate obstruction 35%, oropharyngeal (tonsil) obstruction 76%, tongue base obstruction 32%, supraglottic obstruction 31%, and multi-level obstruction 60%. DISE led to a change in the conventional surgical approach in 45% (95% CI: 29-60%) of patients with OSAHS, providing individualized treatment plans. Postoperative symptoms and sleep-related parameters improved significantly compared to preoperative values, with DISE findings possibly enhancing surgical success rates and potentially avoiding unnecessary procedures. CONCLUSION: In some cases, DISE may potentially lead to alterations in conventional surgical approaches for children with OSAHS who had no history of upper airway surgery, craniofacial abnormalities, or other syndromes.. The results of our meta-analysis were in favor of DISE-directed approach for pediatric conventional OSAHS. However, further high-quality randomized controlled trials (RCTs) are warranted in future research to investigate the role of DISE in the management of pediatric OSAHS.

Risk Factors of Contrast Agent Intravasation With Sulfur Hexafluoride Microbubble During Hysterosalpingo-Contrast Sonography.

OBJECTIVES: To analyze the risk factors of sulfur hexafluoride microbubble contrast agent intravasation during hysterosalpingo-contrast sonography (HyCoSy), and to explore a simple prediction model by the obvious clinical history. METHODS: This was a retrospective study included 299 infertility women who had undergone HyCoSy examination from July 1, 2018 to June 31, 2019. The factors were recorded, including age, endometrial thickness, balloon length, infertility type, history of intrauterine surgery, history of pelvic surgery, and tubal patency. The method of multivariate logistic regression analysis was adopted to analyze the risk factors affecting the contrast agent intravasation, and the receiver operating characteristic curves were plotted to test their efficacy. RESULTS: Secondary infertility, a history of intrauterine surgery, thin endometrial thickness, and tubal obstruction were all risk factors of the occurrence of intravasation (P < .05). And the area under the receiver operating characteristic curves of the multifactor-combined prediction model of the intravasation was significantly larger than that of single-factor. CONCLUSIONS: Sonographers and gynecologists should be familiar with the risk factors of intravasation and select the appropriate timing of HyCoSy toward reducing the occurrence of intravasation and other complications after thoroughly explaining and communicating with the patients.

The Tumor Necrosis Factor-α Level in Platelet-Rich Plasma Might Be Associated with Treatment Outcome in Patients with Interstitial Cystitis/Bladder Pain Syndrome or Recurrent Urinary Tract Infection.

Using platelet-rich plasma (PRP) injections to treat urological diseases has attracted great attention. This study investigated the impact of cytokine concentrations in PRP on the treatment outcome of patients with recurrent urinary tract infection (rUTI) and interstitial cystitis/bladder pain syndrome (IC/BPS). Forty patients with IC/BPS and twenty-one patients with rUTI were enrolled for four-monthly repeated PRP injections. PRP was collected at the first injection and analyzed with multiplex immunoassays for 12 target cytokines. In patients with IC/BPS, a Global Response Assessment (GRA) score ≥ 2 was defined as a successful outcome. In rUTI patients, ≤2 episodes of UTI recurrence during one year of follow-up was considered a successful outcome. Nineteen (47.5%) patients with IC/BPS and eleven (52.4%) patients with rUTI had successful outcomes. The IC/BPS patients with successful outcomes had significantly lower levels of tumor necrosis factor-α (TNF-α) in their PRP than those with unsuccessful outcomes (p = 0.041). The rUTI patients with successful outcomes also had a lower level of TNF-α (p = 0.025) and a higher level of epidermal growth factor (p = 0.035) and transforming growth factor-ß2 (p = 0.024) in PRP than those with unsuccessful outcomes. A lower level of TNF-α in PRP might be a potentially predictive factor of treatment outcome.

Transcriptomic and Metabolomic Investigation on Leaf Necrosis Induced by ZmWus2 Transient Overexpression in Nicotiana benthamiana.

WUSCHEL (WUS) is a crucial transcription factor in regulating plant stem cell development, and its expression can also improve genetic transformation. However, the ectopic expression of WUS always causes pleiotropic effects during genetic transformation, making it important to understand the regulatory mechanisms underlying these phenomena. In our study, we found that the transient expression of the maize WUS ortholog ZmWus2 caused severe leaf necrosis in Nicotiana benthamiana. We performed transcriptomic and non-target metabolomic analyses on tobacco leaves during healthy to wilted states after ZmWus2 transient overexpression. Transcriptomic analysis revealed that ZmWus2 transformation caused active metabolism of inositol trisphosphate and glycerol-3-phosphate, while also upregulating plant hormone signaling and downregulating photosystem and protein folding pathways. Metabolomic analysis mainly identified changes in the synthesis of phenylpropanoid compounds and various lipid classes, including steroid synthesis. In addition, transcription factors such as ethylene-responsive factors (ERFs), the basic helix-loop-helix (bHLH) factors, and MYBs were found to be regulated by ZmWus2. By integrating these findings, we developed a WUS regulatory model that includes plant hormone accumulation, stress responses, lipid remodeling, and leaf necrosis. Our study sheds light on the mechanisms underlying WUS ectopic expression causing leaf necrosis and may inform the development of future genetic transformation strategies.

Quantitative Analysis of Flavonoids in Fruiting Bodies of Sanghuangporus Using Ultra-High-Performance Liquid Chromatography Coupled with Triple Quadrupole Mass Spectrometry.

A rapid, precise, and dependable method for quantifying flavonoids in the fruiting bodies of Sanghuangporus was established using ultra-high-performance liquid chromatography coupled with triple quadrupole mass spectrometry (UHPLC-QQQ-MS/MS). Separation was achieved using a ZORBAX Eclipse Plus C18 column (1.8 µm, 3.0 mm × 100 mm) with a 15 min gradient of a mobile phase consisting of 0.01% aqueous formic acid and 2 mm/L ammonium formate (mobile phase A), and 0.01% formic acid and 2 mm/L ammonium formate in methanol (mobile phase B). A mass spectrometry analysis was performed using the multiple reaction monitoring (MRM) mode with an electrospray ion source. This method enabled the simultaneous detection of 10 flavonoids (sakuranetin, quercitrin, myricitrin, kaempferol, luteolin, rutin, hyperoside, kaempferol-3-O-rutinoside, catechin, and catechin gallate) in the fruiting bodies of Sanghuangporus. Additionally, we applied this method to analyze the flavonoid content in fruiting bodies of various Sanghuangporus species. The results revealed substantial variations in flavonoid content, up to a 100-fold difference, among different species, with myricitrin, hyperoside, and rutin identified as the most abundant flavonoids. This protocol serves as a valuable tool for quantifying flavonoid compounds in different Sanghuangporus species or under diverse cultivation conditions, particularly for identifying species with high levels of specific flavonoid compounds.

Stomach cancer burden in China: Epidemiology and prevention.

In 2020, stomach cancer was the fifth most commonly diagnosed cancer and the fourth leading cause of cancer-related death worldwide. Due to the relatively huge population base and the poor survival rate, stomach cancer is still a threat in China, and accounts for nearly half of the cases worldwide. Fortunately, in China, the incidence and mortality rates of stomach cancer presented a declining trend owing to the change of individual life styles and the persistent efforts to prevent stomach cancer from the governments at all levels. Helicobacter pylori (H. pylori) infection, poor eating habits, smoking, history of gastrointestinal disorders, and family history of stomach cancer are the main risk factors for stomach cancer in China. As a result, by taking risk factors for stomach cancer into account, specific preventive measures, such as eradicating H. pylori and implementing stomach cancer screening projects, should be taken to better prevent and decrease the burden of stomach cancer.

Lung cancer burden and trends from 2000 to 2018 in China: Comparison between China and the United States.

Objective: This study aims to provide an analysis of the current status and trends of lung cancer incidence and mortality rates in China, comparing trends with those in the United States (U.S.). Methods: Data on lung cancer incidence and mortality rates spanning 2000 to 2018 were extracted from the China Cancer Registry Annual Report and the Surveillance, Epidemiology, and End Results database for China and the U.S., respectively. Crude incidence and mortality rates were calculated by sex and age, with age-standardized incidence rates (ASIR) and mortality rates (ASMR) calculated using the Segi-Doll world standard population. Trend analyses employed Joinpoint regression models to determine average annual percentage change (AAPC). The study also assessed the proportion of new cases and deaths by sex and age. Results: In 2018, the ASIR of lung cancer for males in China was 50.72 per 100,000 and the ASMR was 39.69 per 100,000, the ASIR for females was 26.25 per 100,000 and the ASMR was 15.24 per 100,000. Both ASIR and ASMR were higher in males and the highest in the population aged 65 years and older, with the lowest among those aged 20-49 years. In China, female ASIR demonstrated an increasing trend (AAPC: 1.16%), while ASMR decreased in both sexes (AAPCs: -0.48% for males, -1.00% for females). The U.S. exhibited decreasing trends in both ASIR and ASMR across sexes and age groups. Conclusions: The study identified an increasing trend in lung cancer incidence among females and a decreasing mortality trend in both sexes in China. These trends are likely linked to factors such as smoking prevalence, advancements in cancer screening, and improved medical care. The findings underscore the need for tailored lung cancer prevention measures in China, particularly the reinforcement of anti-smoking policies.

Improving diagnosing performance for malignant parotid gland tumors using machine learning with multifeatures based on diffusion-weighted magnetic resonance imaging.

In this study, the performance of machine learning in classifying parotid gland tumors based on diffusion-related features obtained from the parotid gland tumor, the peritumor parotid gland, and the contralateral parotid gland was evaluated. Seventy-eight patients participated in this study and underwent magnetic resonance diffusion-weighted imaging. Three regions of interest, including the parotid gland tumor, the peritumor parotid gland, and the contralateral parotid gland, were manually contoured for 92 tumors, including 20 malignant tumors (MTs), 42 Warthin tumors (WTs), and 30 pleomorphic adenomas (PMAs). We recorded multiple apparent diffusion coefficient (ADC) features and applied a machine-learning method with the features to classify the three types of tumors. With only mean ADC of tumors, the area under the curve of the classification model was 0.63, 0.85, and 0.87 for MTs, WTs, and PMAs, respectively. The performance metrics were improved to 0.81, 0.89, and 0.92, respectively, with multiple features. Apart from the ADC features of parotid gland tumor, the features of the peritumor and contralateral parotid glands proved advantageous for tumor classification. Combining machine learning and multiple features provides excellent discrimination of tumor types and can be a practical tool in the clinical diagnosis of parotid gland tumors.

Improving interobserver agreement and performance of deep learning models for segmenting acute ischemic stroke by combining DWI with optimized ADC thresholds.

OBJECTIVES: To examine the role of ADC threshold on agreement across observers and deep learning models (DLMs) plus segmentation performance of DLMs for acute ischemic stroke (AIS). METHODS: Twelve DLMs, which were trained on DWI-ADC-ADC combination from 76 patients with AIS using 6 different ADC thresholds with ground truth manually contoured by 2 observers, were tested by additional 67 patients in the same hospital and another 78 patients in another hospital. Agreement between observers and DLMs were evaluated by Bland-Altman plot and intraclass correlation coefficient (ICC). The similarity between ground truth (GT) defined by observers and between automatic segmentation performed by DLMs was evaluated by Dice similarity coefficient (DSC). Group comparison was performed using the Mann-Whitney U test. The relationship between the DSC and ADC threshold as well as AIS lesion size was evaluated by linear regression analysis. A p < .05 was considered statistically significant. RESULTS: Excellent interobserver agreement and intraobserver repeatability in the manual segmentation (all ICC > 0.98, p < .001) were achieved. The 95% limit of agreement was reduced from 11.23 cm2 for GT on DWI to 0.59 cm2 for prediction at an ADC threshold of 0.6 × 10-3 mm2/s combined with DWI. The segmentation performance of DLMs was improved with an overall DSC from 0.738 ± 0.214 on DWI to 0.971 ± 0.021 on an ADC threshold of 0.6 × 10-3 mm2/s combined with DWI. CONCLUSIONS: Combining an ADC threshold of 0.6 × 10-3 mm2/s with DWI reduces interobserver and inter-DLM difference and achieves best segmentation performance of AIS lesions using DLMs. KEY POINTS: • Higher Dice similarity coefficient (DSC) in predicting acute ischemic stroke lesions was achieved by ADC thresholds combined with DWI than by DWI alone (all p < .05). • DSC had a negative association with the ADC threshold in most sizes, both hospitals, and both observers (most p < .05) and a positive association with the stroke size in all ADC thresholds, both hospitals, and both observers (all p < .001). • An ADC threshold of 0.6 × 10-3 mm2/s eliminated the difference of DSC at any stroke size between observers or between hospitals (p = .07 to > .99).

Byproduct formation during the biosynthesis of spinosyn A and evidence for an enzymatic interplay to prevent its formation.

Biosynthesis of spinosyn A in Saccharopolyspora spinosa involves a 1,4-dehydration followed by an intramolecular [4 + 2]-cycloaddition catalyzed by SpnM and SpnF, respectively. The cycloaddition also takes place in the absence of SpnF leading to questions regarding its mechanism of catalysis and biosynthetic role. Substrate analogs were prepared with an unactivated dienophile or an acyclic structure and found to be unreactive consistent with the importance of these features for cyclization. The SpnM-catalyzed dehydration reaction was also found to yield a byproduct corresponding to the C11 = C12 cis isomer of the SpnF substrate. This byproduct is stable both in the presence and absence of SpnF; however, relative production of the SpnM product and byproduct could be shifted in favor of the former by including SpnF or the dehydrogenase SpnJ in the reaction. This result suggests a potential interplay between the enzymes of spinosyn A biosynthesis that may help to improve the efficiency of the pathway.

Burden of liver cancer: From epidemiology to prevention.

In this review, we offer a concise overview of liver cancer epidemiology in China and worldwide from the official databases of GLOBOCAN 2020 and the National Cancer Registry in China. We also summarized the evidence for the main risk factors associated with liver cancer risk and discuss strategies implemented in China to control the liver cancer burden. Overall, liver cancer was the sixth most commonly diagnosed cancer and the third leading cause of cancer-related death worldwide in 2020. Although China contributed to nearly half of cases across the world alone, the incidence and mortality rates of liver cancer presented a declining trend owing to the persistent efforts from the governments at all levels. The current liver cancer burden in China still faces an arduous challenge due to the relatively large population base as well as the substantially low survival rate (12.1%). To better control the liver cancer burden with the lowest cost, specific measures should be conducted by reducing exposure to established risk factors such as hepatitis B infection and aflatoxin. The promotion of surveillance is also an important method to prolong the survival of liver cancer. This review will provide basic information for future direction on the control of liver cancer burden.

Colorectal cancer burden, trends and risk factors in China: A review and comparison with the United States.

Objective: China and the United States (the U.S.) have the heaviest colorectal cancer (CRC) burden with considerable variations in temporal trends. This study aims to analyze the temporal patterns of CRC burden and its risk factors in China and the U.S. across the past three decades. Methods: Data were extracted from the Global Burden of Disease (GBD) Study in 2019, including cases, deaths, disability-adjusted life-years (DALYs), age-standardized rate (ASR), and summary exposure value (SEV) of CRC in China and the U.S. between 1990 and 2019. Annual average percentage changes (AAPCs) of CRC burden were calculated using the Joinpoint regression model. The mortality in CRC attributable to potential risk factors was characterized by countries, gender, and age groups. Results: In 2019, there were 607,900 and 227,241 CRC cases, and 261,777 and 84,026 CRC deaths in China and the U.S., respectively. The age-standardized incidence rate (ASIR) was 30.55 per 100,000 in China and 41.86 per 100,000 in the U.S., and the age-standardized mortality rate (ASMR) was 13.86 per 100,000 in China and 14.77 per 100,000 in the U.S. CRC incidence, mortality, and DALY rate in the U.S. showed downward trends in the past three decades (AAPC=-0.47, -1.06, and -0.88, respectively), while upward trends were observed in China (AAPC=3.11, 1.05, and 0.91, respectively). Among the cause of CRC, the leading risk factor contributing to CRC death was low milk in China and smoking in the U.S., respectively. Conclusions: From 1990 to 2019, the burden of CRC in China increased dramatically, particularly for males and middle-aged and elderly people. The management of the major risk factors associated with the high burden of CRC should be enhanced.

A New Small-Molecule Compound, Q308, Silences Latent HIV-1 Provirus by Suppressing Tat- and FACT-Mediated Transcription.

Eliminating the latent HIV reservoir remains a difficult problem for creating an HIV functional cure or achieving remission. The "block-and-lock" strategy aims to steadily suppress transcription of the viral reservoir and lock the HIV promoter in deep latency using latency-promoting agents (LPAs). However, to date, most of the investigated LPA candidates are not available for clinical trials, and some of them exhibit immune-related adverse reactions. The discovery and development of new, active, and safe LPA candidates for an HIV cure are necessary to eliminate residual HIV-1 viremia through the block-and-lock strategy. In this study, we demonstrated that a new small-molecule compound, Q308, silenced the HIV-1 provirus by inhibiting Tat-mediated gene transcription and selectively downregulating the expression levels of the facilitated chromatin transcription (FACT) complex. Strikingly, Q308 induced the preferential apoptosis in HIV-1 latently infected cells, indicating that Q308 may reduce the size of the viral reservoir and thus further prevent viral rebound. These findings highlight that Q308 is a novel and safe anti-HIV-1 inhibitor candidate for a functional cure.