Genomic and immune heterogeneity of multiple synchronous lung adenocarcinoma at different developmental stages.

Multiple synchronous lung cancers (MSLCs) constitute a unique subtype of lung cancer. To explore the genomic and immune heterogeneity across different pathological stages of MSLCs, we analyse 16 MSLCs from 8 patients using single-cell RNA-seq, single-cell TCR sequencing, and bulk whole-exome sequencing. Our investigation indicates clonally independent tumours with convergent evolution driven by shared driver mutations. However, tumours from the same individual exhibit few shared mutations, indicating independent origins. During the transition from pre-invasive to invasive adenocarcinoma, we observe a shift in T cell phenotypes characterized by increased Treg cells and exhausted CD8+ T cells, accompanied by diminished cytotoxicity. Additionally, invasive adenocarcinomas exhibit greater neoantigen abundance and a more diverse TCR repertoire, indicating heightened heterogeneity. In summary, despite having a common genetic background and environmental exposure, our study emphasizes the individuality of MSLCs at different stages, highlighting their unique genomic and immune characteristics.

Integrating respiratory microbiome and host immune response through machine learning for respiratory tract infection diagnosis.

At present, the diagnosis of lower respiratory tract infections (LRTIs) is difficult, and there is an urgent need for better diagnostic methods. This study enrolled 136 patients from 2020 to 2021 and collected bronchoalveolar lavage fluid (BALF) specimens. We used metatranscriptome to analyze the lower respiratory tract microbiome (LRTM) and host immune response. The diversity of the LRTM in LRTIs significantly decreased, manifested by a decrease in the abundance of normal microbiota and an increase in the abundance of opportunistic pathogens. The upregulated differentially expressed genes (DEGs) in the LRTIs group were mainly enriched in infection immune response-related pathways. Klebsiella pneumoniae had the most significant increase in abundance in LRTIs, which was strongly correlated with host infection or inflammation genes TNFRSF1B, CSF3R, and IL6R. We combined LRTM and host transcriptome data to construct a machine-learning model with 12 screened features to discriminate LRTIs and non-LRTIs. The results showed that the model trained by Random Forest in the validate set had the best performance (ROC AUC: 0.937, 95% CI: 0.832-1). The independent external dataset showed an accuracy of 76.5% for this model. This study suggests that the model integrating LRTM and host transcriptome data can be an effective tool for LRTIs diagnosis.

Thyroid function and preeclampsia: a two-sample bidirectional Mendelian randomization study.

BACKGROUND: Thyroid dysfunction has been associated with preeclampsia (PE) during pregnancy, but the observational results are conflicting. Our study aims to investigate the causal association and direction between genetically predicted effects of thyroid function on PE and vice versa via two large summary genetic data. METHODS: We conducted a two-sample bidirectional Mendelian randomization (MR) study using genome-wide association studies (GWAS) summary data from two primarily European cohorts: the ThyroidOmics Consortium and the FinnGen Biobank. We applied the random effects inverse variance weighted (IVW) as our main analysis. MR-Egger and weighted median were used for sensitivity analysis. Statistical analysis was performed using the R program (version 4.3.0) with the two-sample package (version 0.5.6). RESULTS: The results suggest that genetically predicted hyperthyroidism is causally associated with PE during pregnancy [ß = 0.06, 95% confidence interval (CI): 1.01-1.12; P = 0.02], and genetically predicted hypothyroidism is also causally associated with PE during pregnancy (ß = 0.11, 95% CI: 1.03-1.21; P = 0.01). These effects were further confirmed with sensitivity analysis. Conversely, preeclampsia is not associated with the risk of thyroid dysfunction in the reverse MR results: thyroid-stimulating hormone (ß = 0.00, P = 0.92), free thyroxine (FT4) (ß = -0.01, P = 0.56), triiodothyronine (FT3) (ß = -0.00, P = 0.72), FT3/FT4 (ß = -0.01, P = 0.38), thyroid peroxidase antibodies (ß = -0.01, P = 0.64), hyperthyroidism (ß = -0.11, P = 0.29) and hypothyroidism (ß = 0.04, P = 0.12). CONCLUSION: Our study suggests that hyper-/hypo-thyroidism causally affected preeclampsia, while PE is not causally associated with thyroid dysfunctions.

Investigation of linear energy transfer (LET)-dependence behavior and dosimetric response of a flat-panel detector in pencil beam scanning proton therapy.

PURPOSE: This study aims to elucidate the dependence of the flat-panel detector's response on the linear energy transfer (LET) and evaluate the practical viability of employing flat-panel detectors in proton dosimetry applications through LET-dependent correction factors. METHODS: The study assessed the flat-panel detector's response across varying depths using solid water and distinct 100, 150, and 200 MeV proton beams by comparing the flat-panel readings against reference doses measured with an ionization chamber. A Monte Carlo code was used to derive LET values, and an LET-dependent response correction factor was determined based on the ratio of the uncorrected flat-panel dose to the ionization chamber dose. The implications of this under-response correction were validated by applying it to a measurement involving a spread-out Bragg peak (SOBP), followed by a comparative analysis against doses calculated using the Monte Carlo code and MatriXX ONE measurement. RESULTS: The association between LET and the flat-panel detector's under-response displayed a positive correlation that intensified with increasing LET values. Notably, with a 10 keV/µm LET value, the detector's under-response reached 50 %, while the measurement points in the SOBP demonstrated under-response greater than 20 %. However, post-correction, the adjusted flat-panel profile closely aligned with the Monte Carlo profile, yielding a 2-dimensional 3 %/3mm gamma passing rate of 100 % at various verification depths. CONCLUSION: This study successfully defined the link between LET and the responsiveness of flat-panel detectors for proton dosimetric measurements and established a foundational framework for integrating flat-panel detectors in clinical proton dosimetry applications.

GABA Analogue HSK16149 in Chinese Patients With Diabetic Peripheral Neuropathic Pain: A Phase 3 Randomized Clinical Trial.

Importance: Many patients with diabetic peripheral neuropathic pain (DPNP) experience inadequate relief, despite best available medical treatments. There are no approved and effective therapies for patients with DPNP in China. Objective: To evaluate the efficacy and safety of capsules containing γ-aminobutyric acid (GABA) analogue HSK16149 in the treatment of Chinese patients with DPNP. Design, Setting, and Participants: This phase 2 to 3 adaptive randomized clinical trial was multicenter, double blind, and placebo and pregabalin controlled. The trial started on December 10, 2020, and concluded on July 8, 2022. In stage 1, various doses of HSK16149 were evaluated to determine safety and efficacy for stage 2. The second stage then validated the efficacy and safety of the recommended dose. Intervention: In stage 1, enrolled patients (n = 363) were randomized 1:1:1:1:1:1 to 4 HSK16149 doses (40, 80, 120, or 160 mg/d), pregabalin (300 mg/d), or placebo. In stage 2, patients (n = 362) were randomized 1:1:1 to receive HSK16149, 40 or 80 mg/d, or placebo. The final efficacy and safety analysis pooled data from patients receiving the same treatment. Main Outcomes and Measures: The primary efficacy end point in stage 1 was the change from baseline in average daily pain score (ADPS) at week 5. The primary efficacy end point in stage 2 was the change from baseline in ADPS at week 13. When the final statistical analysis was performed, the P values calculated from the independent data of each phase were combined using the weighted inverse normal method to make statistical inferences. Results: Of 725 randomized patients in the full-analysis set (393 men [54.2%]; mean [SD] age, 58.80 [9.53] years; 700 [96.6%] of Han Chinese ethnicity), 177 received placebo; 178, HSK16149, 40 mg/d; 179, HSK16149, 80 mg/d; 66, HSK16149, 120 mg/d; 63, HSK16149, 160 mg/d; and 62, pregabalin, 300 mg/d. A total of 644 patients (88.8%) completed the study. The 40- and 80-mg/d doses of HSK16149 were recommended in stage 2. At week 13, the ADPS mean (SD) change from baseline was -2.24 (1.55) for the 40-mg/d and -2.16 (1.79) for 80-mg/d groups and -1.23 (1.68) for the placebo group, showing statistical significance for both HSK16149 doses vs placebo (both P < .001). In a safety set (n = 726), 545 patients (75.1%) had adverse events, which were generally mild to moderate, with dizziness and somnolence being the most common. Conclusions and Relevance: Forty- and eighty-mg/d doses of HSK16149 were recommended for treating patients with DPNP in China. The efficacy of HSK16149 capsules was superior to placebo in all groups for relieving DPNP and appeared well tolerated. Trial Registration: ClinicalTrials.gov Identifier: NCT04647773.

Efficacy and Safety of Pemafibrate, a Novel Selective PPARα Modulator in Chinese Patients with Dyslipidemia: A Double-Masked, Randomized, Placebo- and Active-Controlled Comparison Trial.

AIMS: Pemafibrate substantially lowers serum triglyceride (TG) levels and increases high-density lipoprotein cholesterol (HDL-C) levels primarily in Japan, but it has not been evaluated in China. We aimed to confirm the efficacy and safety of pemafibrate in Chinese patients with hypertriglyceridemia and low HDL-C levels by comparing placebo and fenofibrate. METHODS: A multicenter, double-masked trial was conducted in China involving 344 patients with high TG and low HDL-C levels randomly assigned to one of four groups: pemafibrate 0.2 mg/d, pemafibrate 0.4 mg/d, fenofibrate 200 mg/d, or placebo for 12 weeks. The primary endpoint was the percentage change in fasting TG levels. RESULTS: The percentage change in TG levels from baseline was -34.1%, -44.0%, -30.5%, and 6.5% in the pemafibrate 0.2 mg/d, pemafibrate 0.4 mg/d, fenofibrate 200 mg/d, and placebo groups, respectively. Pemafibrate 0.4 mg/d significantly reduced TG levels compared with that in both placebo (p＜0.0001) and fenofibrate groups (p=0.0083). Significant improvements in HDL-C, remnant cholesterol, and apolipoprotein A1 levels were also observed with both doses of pemafibrate than with the placebo. Pemafibrate showed significantly smaller changes in alanine aminotransferase, aspartate aminotransferase, and serum creatinine levels than those with fenofibrate. CONCLUSIONS: In Chinese patients, pemafibrate exhibited superior efficacy in improving TG levels and enhanced hepatic and renal safety compared to fenofibrate. Thus, pemafibrate may represent a promising therapeutic option for dyslipidemia in Chinese patients.

Role of gut microbiota in Crohn's disease pathogenesis: Insights from fecal microbiota transplantation in mouse model.

BACKGROUND: Inflammatory bowel disease, particularly Crohn's disease (CD), has been associated with alterations in mesenteric adipose tissue (MAT) and the phenomenon termed "creeping fat". Histopathological evaluations showed that MAT and intestinal tissues were significantly altered in patients with CD, with these tissues characterized by inflammation and fibrosis. AIM: To evaluate the complex interplay among MAT, creeping fat, inflammation, and gut microbiota in CD. METHODS: Intestinal tissue and MAT were collected from 12 patients with CD. Histological manifestations and protein expression levels were analyzed to determine lesion characteristics. Fecal samples were collected from five recently treated CD patients and five control subjects and transplanted into mice. The intestinal and mesenteric lesions in these mice, as well as their systemic inflammatory status, were assessed and compared in mice transplanted with fecal samples from CD patients and control subjects. RESULTS: Pathological examination of MAT showed significant differences between CD-affected and unaffected colons, including significant differences in gut microbiota structure. Fetal microbiota transplantation (FMT) from clinically healthy donors into mice with 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced CD ameliorated CD symptoms, whereas FMT from CD patients into these mice exacerbated CD symptoms. Notably, FMT influenced intestinal permeability, barrier function, and levels of proinflammatory factors and adipokines. Furthermore, FMT from CD patients intensified fibrotic changes in the colon tissues of mice with TNBS-induced CD. CONCLUSION: Gut microbiota play a critical role in the histopathology of CD. Targeting MAT and creeping fat may therefore have potential in the treatment of patients with CD.

CD19+CD73+ B cells infiltration indicates poor prognosis and unfavorable responses to immunotherapy in gastric cancer.

OBJECTIVES: Cluster of Differentiation 73 (CD73) is expressed on immune cells and plays a significant role in tumor inhibition by suppressing antitumor immunity. The objectives of this study were to explore the expression and functional mechanisms of CD73 on B cells in patients with gastric cancer (GC). METHODS: The prognostic significance of CD19+CD73+ B cells was evaluated in 390 GC patients through dual immunohistochemistry staining. Flow cytometry was employed to analyze the phenotype of the CD19 subpopulation using fresh tumor and non-tumor tissue samples from 8 GC patients. A bioinformatics analysis of CD19+CD73+ B cells was also performed within the scRNA-seq cohort, and the CD19+ B cell subtype was assessed using multiple immunofluorescence staining. RESULTS: The infiltration of CD19+CD73+ B cells was observed to be elevated in gastric cancer (GC) tissue compared to normal tissues. A strong correlation was observed between high CD19+CD73+ B cell infiltration, poor overall survival, and diminished responsiveness to neoadjuvant immunotherapy in GC. These cells emerged as a novel subset of regulatory B cells (Bregs) linked to adenosine metabolism and the exhaustion of CD8+ T cells. The CD19+CD73+ B cells also correlated with the production of immunosuppressive cytokines IL-10 and TGFB1. Further analysis indicated an association between CD19+CD73+ B cells and advanced-stage GC. CONCLUSIONS: The presence of CD19+CD73+ B cells in GC may serve as a prognostic indicator for clinical outcomes and a predictive marker for poor responsiveness to neoadjuvant immunotherapy. The correlation between the presence of CD19+CD73+ B cells and CD8+ T cell exhaustion, along with immunosuppression, highlights the tumor-promoting function of these cells.

Investigating functional mechanisms in the Co-biodegradation of lignite and guar gum under the influence of salinity.

The biodegradation of guar gum by microorganisms sourced from coalbeds can result in low-temperature gel breaking, thereby reducing reservoir damage. However, limited attention has been given to the influence of salinity on the synergistic biodegradation of coal and guar gum. In this study, biodegradation experiments of guar gum and lignite were conducted under varying salinity conditions. The primary objective was to investigate the controlling effects and mechanisms of salinity on the synergistic biodegradation of lignite and guar gum. The findings revealed that salinity had an inhibitory effect on the biomethane production from the co-degradation of lignite and guar gum. The biomethane production declined with increasing salinity levels, decreasing from 120.9 mL to 47.3 mL. Even under 20 g/L salt stress conditions, bacteria in coalbeds could effectively break the gel and the viscosity decreased to levels below 5 mPa s. As salinity increased, the removal rate of soluble chemical oxygen demand (SCOD) decreased from 55.63% to 31.17%, and volatile fatty acids (VFAs) accumulated in the digestion system. High salt environment reduces the intensity of each fluorescence peak. Alterations in salinity led to changes in microbial community structure and diversity. Under salt stress, there was an increased relative abundance of Proteiniphilum and Methanobacterium, ensuring the continuity of anaerobic digestion. Hydrogentrophic methanogens exhibited higher salt tolerance compared to acetoclastic methanogens. These findings provide experimental evidence supporting the use of guar gum fracturing fluid in coalbeds with varying salinity levels.

Vitamin C Alleviates the Risk of Gestational Diabetes Mellitus Associated With Exposure to Metals.

Background: Exposure to heavy metals has been suggested to increase the risk of gestational diabetes mellitus (GDM) through the oxidative stress pathway. The study is aimed at examining whether vitamin C could modify the association between exposure to heavy metals and risk of GDM. Methods: We conducted a case-control study in Taiyuan, China, with 776 GDM cases and 776 controls. Data on vitamin C intake from diet and supplements were collected through questionnaires. Concentrations of metals in participants' blood were measured using inductively coupled plasma-mass spectrometry (ICP-MS). Unconditional logistic regression models were applied to estimate effect modification of vitamin C on the association between heavy metals and GDM. Results: Women with higher blood levels of mercury (Hg) (odds ratio (OR) = 2.36, 95% confidence interval (CI): 1.43, 3.92 and 2.04, 95% CI: 1.20, 3.46 for the second and third vs. the first tertile) and arsenic (As) (OR = 2.46, 95% CI: 1.37, 4.43 and 2.16, 95% CI: 1.12, 4.17 for the second and third vs. the first tertile) exposure were associated with increased risk of GDM among women without vitamin C supplement use and having dietary vitamin C intake < 85 mg/day. We found no significant association with metals among women who took vitamin C supplements and/or dietary vitamin C ≥ 85 mg/day. Significant interactions were observed between vitamin C and exposures to metals (i.e., Hg and As) on the risk of GDM (P interaction = 0.048 and 0.045, respectively). Conclusions: Our study, for the first time, suggests that vitamin C supplement use or higher dietary vitamin C intake during preconception and early pregnancy could alleviate the risk of GDM associated with exposure to As and Hg. The results warrant further investigation.

Source and level of dietary iron influence semen quality by affecting inflammation, oxidative stress and iron utilization levels in boars.

BACKGROUND: Boars fed a mixed form of inorganic and organic iron in excess of the NRC recommended levels still develop anemia, which suggested that the current level and form of iron supplementation in boar diets may be inappropriate. Therefore, 56 healthy Topeka E line boars aged 15-21 months were randomly divided into 5 groups: basal diet supplemented with 96 mg/kg ferrous sulfate (FeSO4) and 54 mg/kg glycine chelated iron (Gly-Fe, control); 80 mg/kg or 115 mg/kg Gly-Fe; 80 mg/kg or 115 mg/kg methionine hydroxyl analogue chelated iron (MHA-Fe, from Calimet-Fe) for 16 weeks. The effects of dietary iron supplementation with different sources and levels on semen quality in boars were investigated. RESULTS: 1) Serum Fe and hemoglobin concentrations were not affected by reduced dietary iron levels in the 80 mg/kg or 115 mg/kg Gly-Fe and MHA-Fe groups compared with the control group (P > 0.05). 2) Serum interleukin-6 (IL-6) and sperm malondialdehyde (MDA) levels in the 80 mg/kg or 115 mg/kg MHA-Fe groups were lower than those in the control group (P < 0.05), and higher serum superoxide dismutase levels and lower MDA levels in the 115 mg/kg MHA-Fe group (P < 0.05). 3) Boars in the 80 mg/kg or 115 mg/kg Gly-Fe and MHA-Fe groups had lower serum hepcidin (P < 0.01), ferritin (P < 0.05), and transferrin receptor (P < 0.01) concentrations, and boars in the 115 mg/kg MHA-Fe group had higher seminal plasma Fe concentrations compared with the control group. 4) Boars in the 80 mg/kg and 115 mg/kg MHA-Fe groups had lower abnormal sperm rate and in situ oscillating sperm ratio compared to the control group at weeks 12 and/or 16 of the trial. However, the effect of Gly-Fe on improving semen quality in boars was not evident. 5) Serum IL-6 level was positively correlated with hepcidin concentration (P < 0.05), which in turn was significantly positively correlated with abnormal sperm rate (P < 0.05). Furthermore, significant correlations were also found between indicators of iron status and oxidative stress and semen quality parameters. CONCLUSIONS: Dietary supplementation with 80 mg/kg or 115 mg/kg MHA-Fe did not induce iron deficiency, but rather reduced serum inflammatory levels and hepcidin concentration, alleviated oxidative stress, increased body iron utilization, and improved semen quality in adult boars.

[Expression of the D930020B18Rik gene in the mouse testis during spermatogenesis: Characteristics and potential role].

OBJECTIVE: To investigate the expression pattern of the D930020B18Rik gene in the testis of the mouse in different stages of development and its possible role in spermatogenesis. METHODS: Using gene expression profile microarray, we identified highly expressed D930020B18Rik in the mouse testis and analyzed the expression pattern of the gene by qPCR, immunohistochemistry, Western blot and immunofluorescence staining, and verified its function and molecular mechanism using bioinformatics analysis, dual-luciferase reporter assay and cell cycle synchronization. RESULTS: The expression of the D930020B18Rik gene remained low in the testis of the mouse and mainly localized in the cytoplasm of spermatogonia during the first 2 postnatal weeks (PNW), increased from the 3rd PNW to sexual maturity, localized in the cytoplasm of spermatogonia and the nuclei of round and elongated spermatids, but was absent in the nuclei of mature sperm. Phylogenetic analysis showed that the D930020B18Rik protein sequence was highly conserved in mammals. Gene set enrichment analysis indicated that D930020B18Rik and its homologous protein might be involved in regulating spermatogenesis of mammals by participating in nucleoplasmic condensation (normalized enrichment score ï¼»NESï¼½ = 1.652, P < 0.01, false discovery rate ï¼»FDRï¼½ = 0.153), meiosis (NES = 1.960, P < 0.01, FDR = 0.001) and formation of microtubule cytoskeleton during mitosis (NES = 1.903, P < 0.01, FDR = 0.009). Dual-luciferase reporter assay revealed that the transcription factors klf5 and foxo1 could identify and bind D930020B18Rik promoters and perform the function of positive or negative transcriptional regulation. CONCLUSION: The D930020B18Rik gene is expressed in the mouse testis in a time- and location-specific manner, highly associated with spermiogenesis, mainly localized in the nuclei of germ cells, and may be involved in the meiosis of spermatocytes and spermiogenesis.

Combined healthy lifestyles and risk of depressive symptoms: A baseline survey in China.

BACKGROUND: Little evidence exists about whether a combination of healthy lifestyle factors is associated with a lower risk of depressive symptoms among Chinese population. We aimed to investigate the association between combined healthy lifestyle factors and risk of depressive symptoms. METHODS: We conducted a baseline survey from July 2021 to December 2023, including 53,642 Chinese adults from general population. A healthy lifestyle score was constructed based on six lifestyle factors (physical activity, smoking status, alcohol consumption, diet, sleep duration, and body mass index). Logistic regression models were used to estimate odds ratios (ORs) and 95 % confidence intervals (CIs) adjusted for confounding variables. RESULTS: Each additional healthy lifestyle score was associated with a 20 % lower risk of having depressive symptoms (OR (95 % CI): 0.80 (0.78-0.81)). Compared with individuals with ≤2 healthy lifestyle factors, individuals with all the six healthy lifestyle factors had a 58 % reduced risk of having depressive symptoms (0.42 (0.37-0.47)). After stratification by gender, education and urbanization, the significant inverse association with healthy lifestyle score was stronger in women, individuals with high education, and urban residents. Besides, the significant negative association between healthy lifestyle score and depressive symptoms remained for different severity of depressive symptoms. LIMITATIONS: Given the cross-sectional nature of data, we cannot make causal inferences. CONCLUSIONS: Our study indicated that adherence to healthy lifestyle factors was associated with a reduced risk of having depressive symptoms among Chinese adults. The observed associations were modified by gender, education and urbanization. These findings warrant further verification in interventional studies.

Investigation of the Rapid Emergence of Colistin Resistance in a Newborn Infected with KPC-2-Producing Hypervirulent Carbapenem-Resistant Klebsiella pneumoniae.

OBJECTIVES: Hypervirulent carbapenem-resistant Klebsiella pneumoniae (hv-CRKp) poses a significant threat to public health. This study reports an infection related to hv-CRKp in a premature infant and reveals its colistin resistance and evolutionary mechanisms within the host. METHODS: Three KPC-producing CRKp strains were isolated from a patient with sepsis and CRKp osteoarthritis who had been receiving colistin antimicrobial therapy. The minimum inhibitory concentrations (MICs) of ceftazidime, ceftazidime-avibactam (CAZ-AVI), meropenem, imipenem, tigecycline, amikacin, minocycline, sulfamethoxazole/trimethoprim, ciprofloxacin, levofloxacin, aztreonam, cefepime, cefoperazone/sulbactam, piperacillin/tazobactam, and colistin were determined using the microbroth dilution method. The whole-genome sequencing analysis was conducted to determine the sequence types (STs), virulence genes, and antibiotic resistance genes of the three CRKp strains. RESULTS: Whole-genome sequencing revealed that all three CRKp strains belonged to the ST11 clone and carried a plasmid encoding blaKPC-2. The three strains all possessed the iucABCDiutA virulence cluster, peg-344 gene, and rmpA/rmpA2 genes, defining them as hv-CRKp. Further experiments and whole-genome analysis revealed that a strain of K. pneuomniae had developed resistance to colistin. The mechanism found to be responsible for colistin resistance was a deletion mutation of approximately 9000 bp including the mgrB gene. CONCLUSION: This study characterizes colistin resistance of the ST11 clone hv-CRKp during colistin treatment and its rapid evolution within the host.

A review on 4D cone-beam CT (4D-CBCT) in radiation therapy: Technical advances and clinical applications.

Cone-beam CT (CBCT) is the most commonly used onboard imaging technique for target localization in radiation therapy. Conventional 3D CBCT acquires x-ray cone-beam projections at multiple angles around the patient to reconstruct 3D images of the patient in the treatment room. However, despite its wide usage, 3D CBCT is limited in imaging disease sites affected by respiratory motions or other dynamic changes within the body, as it lacks time-resolved information. To overcome this limitation, 4D-CBCT was developed to incorporate a time dimension in the imaging to account for the patient's motion during the acquisitions. For example, respiration-correlated 4D-CBCT divides the breathing cycles into different phase bins and reconstructs 3D images for each phase bin, ultimately generating a complete set of 4D images. 4D-CBCT is valuable for localizing tumors in the thoracic and abdominal regions where the localization accuracy is affected by respiratory motions. This is especially important for hypofractionated stereotactic body radiation therapy (SBRT), which delivers much higher fractional doses in fewer fractions than conventional fractionated treatments. Nonetheless, 4D-CBCT does face certain limitations, including long scanning times, high imaging doses, and compromised image quality due to the necessity of acquiring sufficient x-ray projections for each respiratory phase. In order to address these challenges, numerous methods have been developed to achieve fast, low-dose, and high-quality 4D-CBCT. This paper aims to review the technical developments surrounding 4D-CBCT comprehensively. It will explore conventional algorithms and recent deep learning-based approaches, delving into their capabilities and limitations. Additionally, the paper will discuss the potential clinical applications of 4D-CBCT and outline a future roadmap, highlighting areas for further research and development. Through this exploration, the readers will better understand 4D-CBCT's capabilities and potential to enhance radiation therapy.

Effects of basic amino acids on heterocyclic amines and quality characteristics of fried beef patties at low NaCl level.

The impact of basic amino acids (Lysine, Arginine, Histidine) on the formation of total heterocyclic amines (HAs) was investigated in fried beef patties at 1% NaCl level. Different levels of basic amino acids (0.1%, 0.5%, 1%) significantly inhibited the formation of the total and individual HAs at 1% NaCl, and the inhibitory effect was more effective than 3% NaCl (6.19 ng/g, 26.93% inhibition) (P < 0.05). Lys at 1% reduced total HAs the most (2.46 ng/g, 70.88% inhibition), followed by 1% His (2.79 ng/g, 67.03% inhibition) and 1% Arg (3.43 ng/g, 59.51% inhibition). Compared to the 3% NaCl, the quality characteristics (moisture content, frying loss, texture profile, and color) of the fried beef patties were significantly improved when basic amino acids were added at 1% NaCl (P < 0.05). The lipid oxidation of fried beef patties was significantly inhibited by 1% Arg and 1% Lys at 1% NaCl level (P < 0.05). The results indicated that basic amino acids could inhibit the formation of total HAs while maintaining the quality of meat products at low NaCl condition.

Mapping recommendations towards an Asian Code Against Cancer (ACAC) as part of the World Code Against Cancer Framework: an Asian National Cancer Centers Alliance (ANCCA) initiative.

This paper outlines the process undertaken by Asian National Cancer Centers Alliance (ANCCA) members in working towards an Asian Code Against Cancer (ACAC). The process involves: (i) identification of the criteria for selecting the existing set of national recommendations for ACAC (ii) compilation of existing national codes or recommendations on cancer prevention (iii) reviewing the scientific evidence on cancer risk factors in Asia and (iv) establishment of one or more ACAC under the World Code Against Cancer Framework. A matrix of national codes or key recommendations against cancer in ANCCA member countries is presented. These include taking actions to prevent or control tobacco consumption, obesity, unhealthy diet, physical inactivity, alcohol consumption, exposure to occupational and environmental toxins; and to promote breastfeeding, vaccination against infectious agents and cancer screening. ANCCA will continue to serve as a supportive platform for collaboration, development, and advocacy of an ACAC jointly with the International Agency for Research on Cancer/World Health Organization (IARC/WHO).