Comparative analysis of prognostic scoring systems in predicting severity and outcomes of Omicron variant COVID-19 pneumonia.

Background: The global spread of Coronavirus Disease 2019 (COVID-19) underscores the urgent need for reliable methods to forecast the disease's severity and outcome, thereby facilitating timely interventions and reducing mortality rates. This study focuses on evaluating the clinical and laboratory profiles of patients with Omicron variant-induced COVID-19 pneumonia and assessing the efficacy of various scoring systems in prognosticating disease severity and mortality. Methods: In this retrospective analysis, we examined the clinical records of 409 individuals diagnosed with Omicron variant COVID-19 pneumonia. We documented the Pneumonia Severity Index, CURB-65, and MuLBSTA scores within the first 24 h and analyzed the sensitivity, specificity, positive predictive value, negative predictive value, and the area under the receiver operating characteristic curve for each scoring system to ascertain their predictive accuracy for disease severity and fatality risk. Results: The cohort's median age was 78 years, predominantly presenting with fever, cough, expectoration, fatigue, and gastrointestinal symptoms. Factors such as expectoration, fatigue, Glasgow Coma Scale score, lactate dehydrogenase levels, procalcitonin, creatinine levels, and co-occurrence of acute respiratory distress syndrome were identified as independent predictors of disease severity. Furthermore, age, oxygenation index, glucose levels, lactate dehydrogenase, and septic shock were independently associated with mortality. For severe disease prediction, the CURB-65, PSI, and MuLBSTA scores demonstrated sensitivities of 65.9%, 63.8%, and 79.7%, respectively, with specificities of 63.8%, 76.8%, and 60.9%, and AUROCs of 0.707, 0.750, and 0.728. To predict mortality risk, these scores at cutoffs of 1.5, 102.5, and 12.5 exhibited sensitivities of 83.3%, 96.3%, and 70.4%, specificities of 59.4%, 60.8%, and 65.4%, and AUROCs of 0.787, 0.850, and 0.736, respectively. Conclusion: The study cohort predominantly comprised elderly individuals with pre-existing health conditions. Elevated lactate dehydrogenase emerged as a significant marker for both disease severity and prognosis, sputum production, gastrointestinal symptoms, GCS score, creatinine, PCT, and ARDS as independent predictors of disease severity, and age, oxygenation index, glucose levels, and septic shock as independent mortality predictors in COVID-19 pneumonia patients. Among the scoring systems evaluated, Pneumonia Severity Index demonstrated superior predictive capability for both disease severity and mortality, suggesting its utility in forecasting the clinical outcomes of Omicron variant COVID-19 pneumonia.

Discovery of a Series of 4-Amide-thiophene-2-carboxyl Derivatives as Highly Potent P2Y14 Receptor Antagonists for Inflammatory Bowel Disease Treatment.

The P2Y14 receptor has been proven to be a potential target for IBD. Herein, we designed and synthesized a series of 4-amide-thiophene-2-carboxyl derivatives as novel potent P2Y14 receptor antagonists based on the scaffold hopping strategy. The optimized compound 39 (5-((5-fluoropyridin-2-yl)oxy)-4-(4-methylbenzamido)thiophene-2-carboxylic acid) exhibited subnanomolar antagonistic activity (IC50: 0.40 nM). Moreover, compound 39 demonstrated notably improved solubility, liver microsomal stability, and oral bioavailability. Fluorescent ligand binding assay confirmed that 39 has the binding ability to the P2Y14 receptor, and molecular dynamics (MD) simulations revealed the formation of a unique intramolecular hydrogen bond (IMHB) in the binding conformation. In the experimental colitis mouse model, compound 39 showed a remarkable anti-IBD effect even at low doses. Compound 39, with a potent anti-IBD effect and favorable druggability, can be a promising candidate for further research. In addition, this work lays a strong foundation for the development of P2Y14 receptor antagonists and the therapeutic strategy for IBD.

A Beam Angle Selection Method to Improve Plan Robustness Against Position Error in Intensity-Modulated Radiotherapy for Left-Sided Breast Cancer.

PURPOSE: We report a dosimetric study in whole breast irradiation (WBI) of plan robustness evaluation against position error with two radiation techniques: tangential intensity-modulated radiotherapy (T-IMRT) and multi-angle IMRT (M-IMRT). METHODS: Ten left-sided patients underwent WBI were selected. The dosimetric characteristics, biological evaluation and plan robustness were evaluated. The plan robustness quantification was performed by calculating the dose differences (Δ) of the original plan and perturbed plans, which were recalculated by introducing a 3-, 5-, and 10-mm shift in 18 directions. RESULTS: M-IMRT showed better sparing of high-dose volume of organs at risk (OARs), but performed a larger low-dose irradiation volume of normal tissue. The greater shift worsened plan robustness. For a 10-mm perturbation, greater dose differences were observed in T-IMRT plans in nearly all directions, with higher ΔD98%, ΔD95%, and ΔDmean of CTV Boost and CTV. A 10-mm shift in inferior (I) direction induced CTV Boost in T-IMRT plans a 1.1 (ΔD98%), 1.1 (ΔD95%), and 1.7 (ΔDmean) times dose differences greater than dose differences in M-IMRT plans. For CTV Boost, shifts in the right (R) and I directions generated greater dose differences in T-IMRT plans, while shifts in left (L) and superior (S) directions generated larger dose differences in M-IMRT plans. For CTV, T-IMRT plans showed higher sensitivity to a shift in the R direction. M-IMRT plans showed higher sensitivity to shifts in L, S, and I directions. For OARs, negligible dose differences were found in V20 of the lungs and heart. Greater ΔDmax of the left anterior descending artery (LAD) was seen in M-IMRT plans. CONCLUSION: We proposed a plan robustness evaluation method to determine the beam angle against position uncertainty accompanied by optimal dose distribution and OAR sparing.

Using molecular fine structure to identify optimal methods of extracting fungal glycogen.

Glycogen is a highly branched glucose polymer that is an energy storage material in fungi and animals. Extraction of glycogen from its source in a way that minimizes its molecular degradation is essential to investigate its native structure. In this study, the following extraction methods were compared: sucrose gradient density ultracentrifugation, thermal alkali, hot alcohol and hot water extractions. Molecular-size and chain-length distributions of glycogen were measured by size-exclusion chromatography and fluorophore-assisted carbohydrate electrophoresis, respectively. These two fine-structure features are the most likely structural characteristics to be degraded during extraction. The results show that the thermal alkali, hot alcohol and hot water extractions degrade glycogen molecular size and/or chain-length distributions, and that sucrose gradient density ultracentrifugation with neither high temperature nor alkaline treatment is the most suitable method for fungal glycogen extraction.

Exploring inflammatory bowel disease therapy targets through druggability genes: a Mendelian randomization study.

Background: Inflammatory bowel disease is an incurable group of recurrent inflammatory diseases of the intestine. Mendelian randomization has been utilized in the development of drugs for disease treatment, including the therapeutic targets for IBD that are identified through drug-targeted MR. Methods: Two-sample MR was employed to explore the cause-and-effect relationship between multiple genes and IBD and its subtypes ulcerative colitis and Crohn's disease, and replication MR was utilized to validate this causality. Summary data-based Mendelian randomization analysis was performed to enhance the robustness of the outcomes, while Bayesian co-localization provided strong evidential support. Finally, the value of potential therapeutic target applications was determined by using the estimation of druggability. Result: With our investigation, we identified target genes associated with the risk of IBD and its subtypes UC and CD. These include the genes GPBAR1, IL1RL1, PRKCB, and PNMT, which are associated with IBD risk, IL1RL1, with a protective effect against CD risk, and GPX1, GPBAR1, and PNMT, which are involved in UC risk. Conclusion: In a word, this study identified several potential therapeutic targets associated with the risk of IBD and its subtypes, offering new insights into the development of therapeutic agents for IBD.

Generalized ratiometric surface-enhanced Raman scattering biosensor for okadaic acid in food based on Au-triggered signal amplification.

BACKGROUND: Reliability and robustness have been recognized as key challenges for Surface-enhanced Raman scattering (SERS) analytical techniques. Quantifying the concentration of an analyte using a single characteristic peak from SERS has been a controversial topic because the Raman signal is susceptible to highly concentrated electromagnetic hotspots, inhomogeneity of SERS substrate, or non-standardization of measurement conditions. Ratiometric SERS strategies have been demonstrated as a promising solution to effectively balance and compensate for signal fluctuations caused by matrix heterogeneity. However, it is not easy to construct ratiometric SERS sensors with monitoring the ratio of two different signal intensities for target analysis. RESULTS: An attempt has been made to develop a novel ratiometric biosensor that can be applied to detect okadaic acid (OA). Aptamer-anchored magnetic particles were first combined with gold-tagged short complementary DNA (Au-cDNA) to create heterogeneous nanostructures. When the target was present, the Au-cDNA was dissociated from nanostructures, and 4-nitrothiophenol (4-NTP) was initiated to reduce to 4-aminothiophenol (4-ATP) in the presence of hydrogen sources. The SERS ratio change of 4-NTP and 4-ATP was finally detected by AuNPs-coated film. OA was successfully quantified, and the detection limit was as low as 2.4524 ng/mL. The constructed biosensor had good stability and reproducibility with a relative standard deviation of less than 4.47%. The proposed method used gold nanoparticles as an intermediate to achieve catalytic signal amplification and subsequently increased the sensitivity of the biosensor. SIGNIFICANCE AND NOVELTY: Catalytic reaction-based ratiometric SERS biosensors combine the multiple advantages of catalytic signal amplification and signal self-calibration and provide new insights into the development of stable, reproducible, and reliable SERS detection techniques. This ratiometric SERS technique offered a universal method that is anticipated to be applicable for the detection of other targets by substituting the aptamer.

Extreme value analysis of the number of student absences in Jiangsu, China: Based on extreme value theory.

Attendance absences have a substantial impact on student's future physical and mental health as well as academic progress. Numerous personal, familial, and social issues are among the causes of student absences. Any kind of absence from school should be minimized. Extremely high rates of student absences may indicate the abrupt commencement of a serious school health crisis or public health crisis, such as the spread of tuberculosis or COVID-19, which provides school health professionals with an early warning. We take the extreme values in absence data as the object and attempt to apply the extreme value theory (EVT) to describe the distribution of extreme values. This study aims to predict extreme instances of student absences. School health professionals can take preventative measures to reduce future excessive absences, according to the predicted results. Five statistical distributions were applied to individually characterize the extreme values. Our findings suggest that EVT is a useful tool for predicting extreme student absences, thereby aiding preventative measures in public health.

The study of the relationship between moderate to severe sleep obstructive apnea and cognitive impairment, anxiety, and depression.

Objective: The present study endeavored to investigate the interconnection between obstructive sleep apnea (OSA) and cognitive function, alongside the manifestations of depression and anxiety. Simultaneously, an analysis was conducted to discern the factors exerting influence upon cognitive function. Methods: A cohort of 102 patients, who had undergone polysomnography (PSG) at Binhu Hospital, Anhui Medical University, between January 2022 and June 2023, was encompassed in the study. Employing the PSG findings, these individuals were classified into two distinct categories: the grouping consisted of those with either negligible or mild OSA, and the other comprised individuals with moderate to severe OSA. Utilizing the Montreal Cognitive Assessment (MoCA-Beijing), Stroop Color and Word Test (SCWT), Digit Span Test (DST), Self-rating Depression Scale (SDS), and Self-rating Anxiety Scale (SAS), scores were recorded and analysed for each of the respective assessments. Additionally, discrepancies and associations between these groups were also scrutinized. Results: The group exhibiting moderate to severe OSA demonstrated significantly elevated measurements in parameters such as neck circumference, BMI, completion times for SCWT-A, B, C, Sleep Inefficiency Index (SIE), SAS, and SDS, in comparison to the No or Mild OSA group. Furthermore, the moderate-severe OSA group manifested notably diminished MoCA scores in areas of visual-spatial and executive function, memory, language, abstraction, delayed recall, orientation, total MoCA score, lowest oxygen saturation (LSaO2), average oxygen saturation, Digit Span Test-backward(DST-b), and Digit Span Test-forward(DST-f), as contrasted with the no-mild OSA group. These inter-group disparities exhibited statistical significance (p < 0.05). The MoCA total score portrayed inverse correlations with age, Apnea-Hypopnea Index (AHI), BMI, SIE, SAS, SDS, CT90%, AHT90%, and Hypoxic Apnea Duration (HAD) (ranging from -0.380 to -0.481, p < 0.05). Conversely, it displayed positive correlations with DST-f, DST-b, LSaO2, and average oxygen saturation (ranging from 0.414 to 0.744, p < 0.05). Neck circumference, AHI, and SAS were autonomously linked to MoCA scores (OR = 1.401, 1.028, 1.070, p < 0.05), while AHI exhibited an independent correlation with SDS and SAS scores (OR = 1.001, p = 0.003). Conclusion: Patients grappling with moderate to severe OSA frequently reveal cognitive impairment and concomitant emotional predicaments encompassing depression and anxiety. These manifestations share an intimate association with AHI, LSaO2, and average oxygen saturation. Notably, anxiety, when coupled with OSA, emerges as an autonomous influential element impinging upon cognitive impairment.

Downregulation of GPX8 in hepatocellular carcinoma: impact on tumor stemness and migration.

PURPOSE: GPX8, which is found in the endoplasmic reticulum lumen, is a member of the Glutathione Peroxidases (GPXs) family. Its role in hepatocellular carcinoma (HCC) is unknown. METHODS: Immunohistochemical staining was used to detect the protein levels of GPX8 in HCC tissue microarrays. A short hairpin RNA lentivirus was used to knock down GPX8, and the main signaling pathways were investigated using transcriptome sequencing and a phosphorylated kinase array. The sphere formation assays, cloning-formation assays and cell migration assays were used to evaluate the stemness and migration ability of HCC cells. Identifying the GPX8-interacting proteins was accomplished through immunoprecipitation and protein mass spectrometry. RESULTS: The GPX8 protein levels were downregulated in HCC patients. Low expression of GPX8 protein was related to early recurrence and poor prognosis in HCC patients. GPX8 knockdown could enhance the stemness and migration ability of HCC cells. Consistently, Based on transcriptome analysis, multiple signaling pathways that include the PI3K-AKT and signaling pathways that regulate the pluripotency of stem cells, were activated after GPX8 knockdown. The downregulation of GPX8 could increase the expression of the tumor stemness markers KLF4, OCT4, and CD133. The in vivo downregulation of GPX8 could also promote the subcutaneous tumor-forming and migration ability of HCC cells. MK-2206, which is a small-molecule inhibitor of AKT, could reverse the tumor-promoting effects both in vivo and in vitro. We discovered that GPX8 and the 71-kDa heat shock cognate protein (Hsc70) have a direct interaction. The phosphorylation of AKT encouraged the translocation of Hsc70 into the nucleus and the expression of the PI3K p110 subunit, thereby increasing the downregulation of GPX8. CONCLUSION: The findings from this study demonstrate the anticancer activity of GPX8 in HCC by inactivating the Hsc70/AKT pathway. The results suggest a possible therapeutic target for HCC.

The changing health effects of air pollution exposure for respiratory diseases: a multicity study during 2017-2022.

BACKGROUND: Multifaceted SARS-CoV-2 interventions have modified exposure to air pollution and dynamics of respiratory diseases. Identifying the most vulnerable individuals requires effort to build a complete picture of the dynamic health effects of air pollution exposure, accounting for disparities across population subgroups. METHODS: We use generalized additive model to assess the likely changes in the hospitalisation and mortality rate as a result of exposure to PM2.5 and O3 over the course of COVID-19 pandemic. We further disaggregate the population into detailed age categories and illustrate a shifting age profile of high-risk population groups. Additionally, we apply multivariable logistic regression to integrate demographic, socioeconomic and climatic characteristics with the pollution-related excess risk. RESULTS: Overall, a total of 1,051,893 hospital admissions and 34,954 mortality for respiratory disease are recorded. The findings demonstrate a transition in the association between air pollutants and hospitalisation rates over time. For every 10 µg/m3 increase of PM2.5, the rate of hospital admission increased by 0.2% (95% CI: 0.1-0.7%) and 1.4% (1.0-1.7%) in the pre-pandemic and dynamic zero-COVID stage, respectively. Conversely, O3-related hospitalization rate would be increased by 0.7% (0.5-0.9%) in the pre-pandemic stage but lowered to 1.7% (1.5-1.9%) in the dynamic zero-COVID stage. Further assessment indicates a shift of high-risk people from children and young adolescents to the old, primarily the elevated hospitalization rates among the old people in Lianyungang (RR: 1.53, 95%CI: 1.46, 1.60) and Nantong (RR: 1.65, 95%CI: 1.57, 1.72) relative to those for children and young adolescents. Over the course of our study period, people with underlying diseases would have 26.5% (22.8-30.3%) and 12.7% (10.8-14.6%) higher odds of having longer hospitalisation and over 6 times higher odds of deaths after hospitalisation. CONCLUSIONS: Our estimates provide the first comprehensive evidence on the dynamic pollution-health associations throughout the pandemic. The results suggest that age and underlying diseases collectively determines the disparities of pollution-related health effect across population subgroups, underscoring the urgency to identifying the most vulnerable individuals to air pollution.

Isolation of a marine-derived yeast with potential applications in industrial nitrite utilizing.

The nitrite efficient utilization microorganism Wickerhamomyces anomalus RZWP01 was identified. Using nitrite and ammonium as the sole nitrogen source, the nitrogen removal rate of W. anomalus RZWP01 was 97.4% and 87.1%, respectively. W. anomalus RZWP01 grew well in the nitrite medium with glucose or xylose as the only carbon source. However, the W. anomalus RZWP01 cannot live on the nitrite medium with lactose, citric acid, and methanol as the only carbon source. The maximal cell concentration occurred in the nitrite medium with glucose as the only carbon source at a C/N ratio of 20 for 48 h, reaching 8.92 × 108 cell mL-1. W. anomalus RZWP01 was the first reported yeast that can efficiently utilize nitrite. The isolation and identification of W. anomalus RZWP01 enriched the microbial resources of nitrite-degrading microorganisms and provided functional microorganisms for the water treatment of sustainable aquaculture.

Macro CD5L+ deteriorates CD8+T cells exhaustion and impairs combination of Gemcitabine-Oxaliplatin-Lenvatinib-anti-PD1 therapy in intrahepatic cholangiocarcinoma.

Intratumoral immune status influences tumor therapeutic response, but it remains largely unclear how the status determines therapies for patients with intrahepatic cholangiocarcinoma. Here, we examine the single-cell transcriptional and TCR profiles of 18 tumor tissues pre- and post- therapy of gemcitabine plus oxaliplatin, in combination with lenvatinib and anti-PD1 antibody for intrahepatic cholangiocarcinoma. We find that high CD8 GZMB+ and CD8 proliferating proportions and a low Macro CD5L+ proportion predict good response to the therapy. In patients with a poor response, the CD8 GZMB+ and CD8 proliferating proportions are increased, but the CD8 GZMK+ proportion is decreased after the therapy. Transition of CD8 proliferating and CD8 GZMB+ to CD8 GZMK+ facilitates good response to the therapy, while Macro CD5L+-CD8 GZMB+ crosstalk impairs the response by increasing CTLA4 in CD8 GZMB+. Anti-CTLA4 antibody reverses resistance of the therapy in intrahepatic cholangiocarcinoma. Our data provide a resource for predicting response of the combination therapy and highlight the importance of CD8+T-cell status conversion and exhaustion induced by Macro CD5L+ in influencing the response, suggesting future avenues for cancer treatment optimization.

Exclusive and Switchable Superoxide Radical Generation by O2-Capture-Based Electron Transfer and Supramolecular Assembly.

Type-I photosensitizers (PSs) can generate free radical anions with a broad diffusion range and powerful damage effect, rendering them highly desirable in various areas. However, it still remains a recognized challenge to develop pure Type-I PSs due to the inefficiency in producing oxygen radical anions through the collision of PSs with nearby substrates. In addition, regulating the generation of oxygen radical anions is also of great importance toward the control of photosensitizer (PS) activities on demand. Herein, a piperazine-based cationic Type-I PS (PPE-DPI) that exhibits efficient intersystem crossing and subsequently captures oxygen molecules through binding O2 to the lone pair of nitrogen in piperazine is reported. The close spatial vicinity between O2 and PPE-DPI strongly promotes the electron transfer reaction, ensuring the exclusive superoxide radical (O2 •-) generation via Type-I process. Particularly, PPE-DPI with cationic pyridine groups is able to associate with cucurbit[7]uril (CB[7]) through host-guest interactions. Thus, supramolecular assembly and disassembly are easily utilized to realize switchable O2 •- generation. This switchable Type-I PS is successfully employed in photodynamic antibacterial control.

Renal Clearable Nanodots-Engineered Erythrocytes with Enhanced Circulation and Tumor Accumulation for Photothermal Therapy of Hepatocellular Carcinoma.

Living cell-mediated nanodelivery system is considered a promising candidate for targeted antitumor therapy; however, their use is restricted by the adverse interactions between carrier cells and nanocargos. Herein, a novel erythrocyte-based nanodelivery system is developed by assembling renal-clearable copper sulfide (CuS) nanodots on the outer membranes of erythrocytes via a lipid fusion approach, and demonstrate that it is an efficient photothermal platform against hepatocellular carcinoma. After intravenous injection of the nanodelivery system, CuS nanodots assembled on erythrocytes can be released from the system, accumulate in tumors in response to the high shear stress of bloodstream, and show excellent photothermal antitumor effect under the near infrared laser irradiation. Therefore, the erythrocyte-mediated nanodelivery system holds many advantages including prolonged blood circulation duration and enhanced tumor accumulation. Significantly, the elimination half-life of the nanodelivery system is 74.75 ± 8.77 h, which is much longer than that of nanodots (33.56 ± 2.36 h). Moreover, the other two kinds of nanodots can be well assembled onto erythrocytes to produce other erythrocyte-based hitchhiking platforms. Together, the findings promote not only the development of novel erythrocyte-based nanodelivery systems as potential platforms for tumor treatment but also their further clinical translation toward personalized healthcare.

Cypermethrin induces Sertoli cell apoptosis through endoplasmic reticulum-mitochondrial coupling involving IP3R1-GRP75-VDAC1.

A widely used type II pyrethroid pesticide cypermethrin (CYP) is one of endocrine disrupting chemicals (EDCs) with anti-androgenic activity to induce male reproductive toxicology. However, the mechanisms have not been fully elucidated. This study was to explore the effects of CYP on apoptosis of mouse Sertoli cells (TM4) and the roles of endoplasmic reticulum (ER)-mitochondria coupling involving 1,4,5-trisphosphate receptor type1-glucose-regulated protein 75-voltage-dependent anion channel 1 (IP3R1-GRP75-VDAC1). TM4 were cultured with different concentrations of CYP. Flow cytometry, calcium (Ca2+) fluorescent probe, transmission electron microscopy and confocal microscopy, and western blot were to examine apoptosis of TM4, mitochondrial Ca2+, ER-mitochondria coupling, and expressions of related proteins. CYP was found to increase apoptotic rates of TM4 significantly. CYP was shown to significantly increase expressions of cleaved caspase-3, cleaved poly ADP-ribose polymerase (PARP). Concentration of mitochondrial Ca2+ was increased by CYP treatment significantly. CYP significantly enhanced ER-mitochondria coupling. CYP was shown to increase expressions of IP3R, Grp75 and VDAC1 significantly. We suggest that CYP induces apoptosis in TM4 cells by facilitating mitochondrial Ca2+ overload regulated by ER-mitochondria coupling involving IP3R1-GRP75-VDAC1. This study identifies a novel mechanism of CYP-induced apoptosis in Sertoli cells.

Artificial intelligence-based diagnosis of standard endoscopic ultrasonography scanning sites in the biliopancreatic system: a multicenter retrospective study.

BACKGROUND: There are challenges for beginners to identify standard biliopancreatic system anatomical sites on endoscopic ultrasonography (EUS) images. Therefore, the authors aimed to develop a convolutional neural network (CNN)-based model to identify standard biliopancreatic system anatomical sites on EUS images. METHODS: The standard anatomical structures of the gastric and duodenal regions observed by EUS was divided into 14 sites. The authors used 6230 EUS images with standard anatomical sites selected from 1812 patients to train the CNN model, and then tested its diagnostic performance both in internal and external validations. Internal validation set tests were performed on 1569 EUS images of 47 patients from two centers. Externally validated datasets were retrospectively collected from 16 centers, and finally 131 patients with 85 322 EUS images were included. In the external validation, all EUS images were read by CNN model, beginners, and experts, respectively. The final decision made by the experts was considered as the gold standard, and the diagnostic performance between CNN model and beginners were compared. RESULTS: In the internal test cohort, the accuracy of CNN model was 92.1-100.0% for 14 standard anatomical sites. In the external test cohort, the sensitivity and specificity of CNN model were 89.45-99.92% and 93.35-99.79%, respectively. Compared with beginners, CNN model had higher sensitivity and specificity for 11 sites, and was in good agreement with the experts (Kappa values 0.84-0.98). CONCLUSIONS: The authors developed a CNN-based model to automatically identify standard anatomical sites on EUS images with excellent diagnostic performance, which may serve as a potentially powerful auxiliary tool in future clinical practice.

Association between gut microbiota and seven gastrointestinal diseases: A Mendelian randomized study.

BACKGROUND: Observational research has shed light on the ability of gut microbes to influence the onset and progression of gastrointestinal diseases. The causal relationships between specific gut microbiomes and various gastrointestinal conditions, however, remain unknown. METHODS: We investigated the relationship between gut microbiota and seven specific gastrointestinal disorders using a robust two-sample Mendelian randomization (MR) approach. The inverse variance-weighted (IVW) method was used as the primary analysis tool in our study. Furthermore, we conducted multiple sensitivity analyses to strengthen the robustness of our findings and ensure the reliability of the IVW method. RESULTS: Our research has discovered significant links between the composition of gut microbiota and a variety of gastrointestinal ailments. We found compelling links between 13 gut microbiota and fatty liver, four gut microbiota and cirrhosis, eight gut microbiota and hepatocellular carcinoma, four gut microbiota and cholelithiasis, 12 gut microbiota and acute pancreatitis, eight gut microbiota and chronic pancreatitis, and 11 gut microbiota and pancreatic cancer. These findings shed light on the intricate relationship between gut microbes and the emergence of these specific gastrointestinal conditions. CONCLUSIONS: The findings of this extensive study not only validate the potential role of specific gut microbiota in gastrointestinal diseases, but also fill a critical gap in previous research. The discovery of these specific gut microbiota is a significant step forward because they may serve as novel and promising biomarkers for both the prevention and treatment of gastrointestinal conditions.

Oral VV116 versus placebo in patients with mild-to-moderate COVID-19 in China: a multicentre, double-blind, phase 3, randomised controlled study.

BACKGROUND: Spread of SARS-CoV-2 led to a global pandemic, and there remains unmet medical needs in the treatment of Omicron infections. VV116, an oral antiviral agent that has potent activity against SARS-CoV-2, was compared with a placebo in this phase 3 study to investigate its efficacy and safety in patients with mild-to-moderate COVID-19. METHODS: This multicentre, double-blind, phase 3, randomised controlled study enrolled adults in hospitals for infectious diseases and tertiary general hospitals in China. Eligible patients were randomly assigned in a 1:1 ratio using permuted block randomisation to receive oral VV116 (0·6 g every 12 h on day 1 and 0·3 g every 12 h on days 2-5) or oral placebo (on the same schedule as VV116) for 5 days. Randomisation stratification factors included SARS-CoV-2 vaccination status and the presence of high-risk factors for progression to severe COVID-19. Inclusion criteria were a positive SARS-CoV-2 test, an initial onset of COVID-19 symptoms 3 days or less before the first study dose, and a score of 2 or more for any target COVID-19-related symptoms in the 24 h before the first dose. Patients who had severe or critical COVID-19 or who had taken any antiviral drugs were excluded from the study. The primary endpoint was the time to clinical symptom resolution for 2 consecutive days. Efficacy analyses were performed on a modified intention-to-treat population, comprising all patients who received at least one dose of VV116 or placebo, tested positive for SARS-CoV-2 nucleic acid, and did not test positive for influenza virus before the first dose. Safety analyses were done on all participants who received at least one dose of VV116 or placebo. This study was registered with ClinicalTrials.gov, NCT05582629, and has been completed. FINDINGS: A total of 1369 patients were randomly assigned to treatment groups and 1347 received either VV116 (n=674) or placebo (n=673). At the interim analysis, VV116 was superior to placebo in reducing the time to sustained clinical symptom resolution among 1229 patients (hazard ratio [HR] 1·21, 95% CI 1·04-1·40; p=0·0023). At the final analysis, a substantial reduction in time to sustained clinical symptom resolution was observed for VV116 compared with placebo among 1296 patients (HR 1·17, 95% CI 1·04-1·33; p=0·0009), consistent with the interim analysis. The incidence of adverse events was similar between groups (242 [35·9%] of 674 patients vs 283 [42·1%] of 673 patients). INTERPRETATION: Among patients with mild-to-moderate COVID-19, VV116 significantly reduced the time to sustained clinical symptom resolution compared with placebo, with no observed safety concerns. FUNDING: Shanghai Vinnerna Biosciences, Shanghai Science and Technology Commission, and the National Key Research and Development Program of China. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

Serial circulating tumor DNA profiling predicts tumor recurrence after liver transplantation for liver cancer.

BACKGROUND: Minimal residual disease (MRD) is proposed to be responsible for tumor recurrence. The role of circulating tumor DNA (ctDNA) to detect MRD, monitor recurrence, and predict prognosis in liver cancer patients undergoing liver transplantation (LT) remains unrevealed. METHODS: Serial blood samples were collected to profile ctDNA mutational changes. Baseline ctDNA mutational profiles were compared with those of matched tumor tissues. Correlations between ctDNA status and recurrence rate (RR) and recurrence-free survival (RFS) were analyzed, respectively. Dynamic change of ctDNA was monitored to predict tumor recurrence. RESULTS: Baseline mutational profiles of ctDNA were highly concordant with those of tumor tissues (median, 89.85%; range 46.2-100%) in the 74 patients. Before LT, positive ctDNA status was associated with higher RR (31.7% vs 11.5%; p = 0.001) and shorter RFS than negative ctDNA status (17.8 vs 19.4 months; p = 0.019). After LT, the percentage of ctDNA positivity decreased (17.6% vs 47.0%; p < 0.001) and patients with positive ctDNA status had higher RR (46.2% vs 21.3%; p < 0.001) and shorter RFS (17.2 vs 19.2 months; p = 0.010). Serial ctDNA profiling demonstrated patients with decreased or constant negative ctDNA status had lower RR (33.3% vs 50.0%; p = 0.015) and favorable RFS (18.2 vs 15.0 months, p = 0.003) than those with increased or constant positive ctDNA status. Serial ctDNA profiling predicted recurrence months ahead of imaging evidence and serum tumor biomarkers. CONCLUSIONS: ctDNA could effectively detect MRD and predict tumor recurrence in liver cancer patients undergone LT.

The associations between high-levels of urine benzophenone-type UV filters (BPs) and changes in serum lipid concentrations.

Little is known about the potential health impacts of benzophenone-type UV filters (BPs) exposure among the general population. In our study conducted in Wuxi, China, we investigated the associations between the concentrations of eight BP-derivatives and five target lipid molecules. We collected basic information, serum, and urine samples from 120 residents aged 9 to 80 in Wuxi. We determined BPs in urine samples and lipid levels in serum samples. Generalized linear models were used to evaluate the differences in ln-transformed serum target lipids levels (µg/L) with different urine BPs quartiles compared to the lowest quartile. Benzophenone-4 (BP-4) had the highest detection rate (95.0%) and geometric mean concentration (1.96 µg/L) among all the BP-derivatives in our study population. The exposure levels of BPs were generally higher in females than in males. Participants in the 9-17 and 18-50 age groups exhibited greater levels of exposure to BPs than those in the 51-80 age group. We observed statistically significant changes in LysoPC (18:0), LysoPE (18:0), ΣLPL, and ΣTL concentrations between the highest and lowest quartiles of BP-4. Similar changes were found in LysoPE (18:0) concentration between the highest and lowest quartiles of ΣBP-3 and ΣBPs. High urine BP concentrations were associated with variations in our target serum lipids involved in neurological and metabolic disorders, and posed a potential health risk. Future studies are warranted to further validate and elucidate our findings.