Numerical Simulation and Parameter Optimization for Water-to-CO2 Flooding in a Strongly Water-Sensitive Reservoir.

Carbon dioxide flooding can accelerate the development of low-permeability reservoirs of the Kexia group in the K region of the T oil field, thus resolving the issue of inadequate water drive effects. This study was focused on the well group 80513 in the K region, and based on the reservoir and fluid parameters, a simulation model of water-sensitive post-CO2 flooding was constructed to refine the gas injection strategy gradually. The injection rate of the continuous gas injection stage was preferred based on the degree of recovery. Multiindicator and multifactor injection and extraction schemes were established to optimize and analyze the key controlling factors, including the gas injection rate, gas injection period, gas-to-water ratio, and bottom-hole flow pressure, in the carbon dioxide gas-to-water alternation process. Recovery efficiency, oil exchange rate, formation pressure, and carbon dioxide storage rate were used as indicators. After 5 years of continuous CO2 flooding, the results indicated that switching to CO2 gas-water alternating flooding was more appropriate for the target block's environment. The best development plan was achieved when the gas injection rates were 1.0 and 1.25 × 104 m3·d-1 for continuous gas injection and CO2 gas-water alternating flooding, respectively, with a gas-water ratio of 1:1, a gas injection cycle of 90 days, and a bottom-hole flow pressure of 25 MPa in the production wells. A comparison between the results revealed that the formation pressure and oil recovery efficiency of this well group significantly increased upon CO2 flooding, and the parameter optimization results were well suited for controlling the gas flurry, offering a versatile model for future development of the block.

Fractal analysis of left ventricular trabeculae in post-STEMI: from acute to chronic phase.

PURPOSE: The temporal evolution of ventricular trabecular complexity and its correlation with major adverse cardiovascular events (MACE) remain indeterminate in patients presenting with acute ST elevation myocardial infarction (STEMI). METHODS: This retrospective analysis enrolled patients undergoing primary percutaneous coronary intervention (pPCI) for acute STEMI, possessing cardiac magnetic resonance (CMR) data in the acute (within 7 days), subacute (1 month after pPCI), and chronic phases (6 months after pPCI) from January 2015 to January 2020 at the three participating sites. Fractal dimensions (FD) were measured for the global, infarct, and remote regions of left ventricular trabeculae during each phase. The potential association of FD with MACE was analyzed using multivariate Cox regression. RESULTS: Among the 200 analyzed patients (182 men; median age, 61 years; age range, 50-66 years), 37 (18.5%) encountered MACE during a median follow-up of 31.2 months. FD exhibited a gradual decrement (global FD at acute, subacute, and chronic phases: 1.253 ± 0.049, 1.239 ± 0.046, 1.230 ± 0.045, p < 0.0001), with a more pronounced decrease observed in patients subsequently experiencing MACE (p < 0.001). The global FD at the subacute phase correlated with MACE (hazard ratio 0.89 (0.82, 0.97), p = 0.01), and a global FD value below 1.26 was associated with a heightened risk. CONCLUSION: In patients post-STEMI, the global FD, serving as an indicator of left ventricular trabeculae complexity, independently demonstrated an association with subsequent major adverse cardiovascular events, beyond factors encompassing left ventricular ejection fraction, indexed left ventricular end-diastolic volume, infarct size, heart rate, NYHA class, and post-pPCI TIMI flow. CRITICAL RELEVANCE STATEMENT: In patients who have had an ST-segment elevation myocardial infarction, global fractal dimension, as a measure of left ventricular trabeculae complexity, provided independent association with subsequent major adverse cardiovascular event. KEY POINTS: • Global and regional FD decreased after STEMI, and more so in patients with subsequent MACE. • Lower global FD at the subacute phase and Δglobal FD from acute to subacute phase were associated with subsequent MACE besides clinical and CMR factors. • Global FD at the subacute phase independently correlated with MACE and global FD value below 1.26 was associated with higher risk.

The relationship between inflammation, impaired glymphatic system, and neurodegenerative disorders: A vicious cycle.

The term "glymphatic" emerged roughly a decade ago, marking a pivotal point in neuroscience research. The glymphatic system, a glial-dependent perivascular network distributed throughout the brain, has since become a focal point of investigation. There is increasing evidence suggesting that impairment of the glymphatic system appears to be a common feature of neurodegenerative disorders, and this impairment exacerbates as disease progression. Nevertheless, the common factors contributing to glymphatic system dysfunction across most neurodegenerative disorders remain unclear. Inflammation, however, is suspected to play a pivotal role. Dysfunction of the glymphatic system can lead to a significant accumulation of protein and waste products, which can trigger inflammation. The interaction between the glymphatic system and inflammation appears to be cyclical and potentially synergistic. Yet, current research is limited, and there is a lack of comprehensive models explaining this association. In this perspective review, we propose a novel model suggesting that inflammation, impaired glymphatic function, and neurodegenerative disorders interconnected in a vicious cycle. By presenting experimental evidence from the existing literature, we aim to demonstrate that: (1) inflammation aggravates glymphatic system dysfunction, (2) the impaired glymphatic system exacerbated neurodegenerative disorders progression, (3) neurodegenerative disorders progression promotes inflammation. Finally, the implication of proposed model is discussed.

Predicting early-onset COPD risk in adults aged 20-50 using electronic health records and machine learning.

Chronic obstructive pulmonary disease (COPD) is a major public health concern, affecting estimated 164 million people worldwide. Early detection and intervention strategies are essential to reduce the burden of COPD, but current screening approaches are limited in their ability to accurately predict risk. Machine learning (ML) models offer promise for improved accuracy of COPD risk prediction by combining genetic and electronic medical record data. In this study, we developed and evaluated eight ML models for primary screening of COPD utilizing routine screening data, polygenic risk scores (PRS), additional clinical data, or a combination of all three. To assess our models, we conducted a retrospective analysis of approximately 329,396 patients in the UK Biobank database. Incorporating personal information and blood biochemical test results significantly improved the model's accuracy for predicting COPD risk, achieving a best performance of 0.8505 AUC, a specificity of 0.8539 and a sensitivity of 0.7584. These results indicate that ML models can be effectively utilized for accurate prediction of COPD risk in individuals aged 20 to 50 years, providing a valuable tool for early detection and intervention.

A comparison of the postoperative outcomes between intraoperative leak testing and no intraoperative leak testing for gastric cancer surgery: a systematic review and meta-analysis.

BACKGROUND: Postoperative anastomotic leakage (PAL) is a serious complication of gastric cancer surgery. Although perioperative management has made considerable progress, anastomotic leakage (AL) cannot always be avoided. The purpose of this study is to evaluate whether intraoperative leak testing (IOLT) can reduce the incidence of PAL and other postoperative outcomes in gastric cancer surgery. MATERIALS AND METHODS: In this meta-analysis, we searched the PubMed, Embase, and Cochrane Library databases for clinical trials to assess the application of IOLT in gastric cancer surgery. All patients underwent laparoscopic radical gastrectomy for gastric cancer surgery. Studies comparing the postoperative outcomes of IOLT and no intraoperative leak testing (NIOLT) were included. Quality assessment, heterogeneity, risk of bias, and the level of evidence of the included studies were evaluated. PAL, anastomotic-related complications, 30-day mortality, and reoperation rates were compared between the IOLT and NIOLT group. RESULTS: Our literature search returned 721 results, from which six trials (a total of 1,666 patients) were included in our meta-analysis. Statistical heterogeneity was low. The primary outcome was PAL. IOLT reduced the incidence of PAL [2.09% vs 6.68%; (RR = 0.31, 95% Cl 0.19-0.53, P < 0.0001]. Anastomotic-related complications, which included bleeding, leakage, and stricture, were significantly higher in the NIOLT group than in the IOLT group [3.24% VS 10.85%; RR = 0.30, 95% Cl 0.18-0.53, P < 0.0001]. Moreover, IOLT was associated with lower reoperation rates [0.94% vs 6.83%; RR = 0.18, 95% CI 0.07-0.43, P = 0.0002]. CONCLUSION: Considering the observed lower incidence of postoperative anastomotic leakage (PAL), anastomotic-related complications, and reoperation rates, IOLT appears to be a promising option for gastric cancer surgery. It warrants further study before potential inclusion in future clinical guidelines.

The Glymphatic Response to the Development of Type 2 Diabetes.

The glymphatic system has recently been shown to be important in neurological diseases, including diabetes. However, little is known about how the progressive onset of diabetes affects the glymphatic system. The aim of this study is to investigate the glymphatic system response to the progressive onset of diabetes in a rat model of type 2 diabetic mellitus. Male Wistar rats (n = 45) with and without diabetes were evaluated using MRI glymphatic tracer kinetics, functional tests, and brain tissue immunohistochemistry. Our data demonstrated that the contrast agent clearance impairment gradually progressed with the diabetic duration. The MRI data showed that an impairment in contrast clearance occurred prior to the cognitive deficits detected using functional tests and permitted the detection of an early DM stage compared to the immuno-histopathology and cognitive tests. Additionally, the quantitative MRI markers of brain waste clearance demonstrated region-dependent sensitivity in glymphatic impairment. The improved sensitivity of MRI markers in the olfactory bulb and the whole brain at an early DM stage may be attributed to the important role of the olfactory bulb in the parenchymal efflux pathway. MRI can provide sensitive quantitative markers of glymphatic impairment during the progression of DM and can be used as a valuable tool for the early diagnosis of DM with a potential for clinical application.

Preoperative CT radiomics of esophageal squamous cell carcinoma and lymph node to predict nodal disease with a high diagnostic capability.

PURPOSE: To develop CT radiomics models of resectable esophageal squamous cell carcinoma (ESCC) and lymph node (LN) to preoperatively identify LN+. MATERIALS AND METHODS: 299 consecutive patients with ESCC were enrolled in the study, 140 of whom were LN+ and 159 were LN-. Of the 299 patients, 249 (from the same hospital) were randomly divided into a training cohort (n = 174) and a test cohort (n = 75). The remaining 50 patients, from a second hospital, were assigned to an external validation cohort. In the training cohort, preoperative contrast-enhanced CT radiomics features of ESCC and LN were extracted, then integrated with clinical features to develop three models: ESCC, LN and combined. The performance of these models was assessed using area under receiver operating characteristic curve (AUC), and F-1 score, which were validated in both the test cohort and external validation cohort. RESULTS: An ESCC model was developed for the training cohort utilizing the 8 tumor radiomics features, and an LN model was constructed using 9 nodal radiomics features. A combined model was constructed using both ESCC and LN extracted features, in addition to cT stage and LN+ distribution. This combined model had the highest predictive ability among the three models in the training cohort (AUC = 0.948, F1-score = 0.878). The predictive ability was validated in both the test and external validation cohorts (AUC = 0.885 and 0.867, F1-score = 0.816 and 0.773, respectively). CONCLUSION: To preoperatively determine LN+, the combined model is superior to models of ESCC and LN alone.

Comparison of the postoperative outcome with and without intraoperative leak testing for sleeve gastrectomy: a systematic review and meta-analysis of 469 588 cases.

OBJECTIVE: Postoperative staple line leakage (SLL) after sleeve gastrectomy (SG) is a rare but serious complication. Many surgeons routinely test anastomosis with an intraoperative leak test (IOLT) as part of the SG procedure. This meta-analysis aims to determine whether an IOLT plays a role in reducing the rate of postoperative staple line related complications in patients who underwent SG. METHODS: The authors searched the PubMed, Web of science, the Cochrane Library, and Clinical Trials.gov databases for clinical studies assessing the application of IOLT in SG. The primary endpoint was the development of postoperative SLL. Secondary endpoints included the postoperative bleeding, 30 days mortality rates, and 30 days readmission rates. RESULTS: Six studies totaling 469 588 patients met the inclusion criteria. Our review found that the SLL rate was 0.38% (1221/ 324 264) in the IOLT group and 0.31% (453/ 145 324) in the no intraoperative leak test (NIOLT) group. Postoperative SLL decreased in the NIOLT group compared with the IOLT group (OR=1.27; 95% CI: 1.14-1.42, P =0.000). Postoperative bleeding was fewer in the IOLT group than that in the NIOLT group (OR 0.79; 95% CI: 0.72-0.87, P =0.000). There was no significant difference between the IOLT group and the NIOLT group regarding 30 days mortality rates and 30 days readmission rates ( P >0.05). CONCLUSION: IOLT was correlated with an increase in SLL when included as a part of the SG procedure. However, IOLT was associated with a lower rate of postoperative bleeding. Thus, IOLT should be considered in SG in the situation of suspected postoperative bleeding.

Left Ventricular Vertical Run-Length Nonuniformity MRI Adds Prognostic Value to MACE in Patients with End-Stage Renal Disease.

BACKGROUND: Vertical run-length nonuniformity (VRLN) is a texture feature representing heterogeneity within native T1 images and reflects the extent of cardiac fibrosis. In uremic cardiomyopathy, interstitial fibrosis was the major histological alteration. The prognostic value of VRLN in patients with end-stage renal disease (ESRD) remains unclear. PURPOSE: To evaluate the prognostic value of VRLN MRI in patients with ESRD. STUDY TYPE: Prospective. POPULATION: A total of 127 ESRD patients (30 participants in the major adverse cardiac events, MACE group). FIELD STRENGTH/SEQUENCE: 3.0 T/steady-state free precession sequence, modified Look-Locker imaging. ASSESSMENT: MRI image qualities were assessed by three independent radiologists. VRLN values were measured in the myocardium on the mid-ventricular short-axis slice of T1 mapping. Left ventricular (LV) mass, LV end-diastolic and end-systolic volume, as well as LV global strain cardiac parameters were measured. STATISTICAL TESTS: The primary endpoint was the incident of MACE from enrollment time to January 2023. MACE is a composite endpoint consisting of all-cause mortality, acute myocardial infarction, stroke, heart failure hospitalization, and life-threatening arrhythmia. Cox proportional-hazards regression was performed to test whether VRLN independently correlated with MACE. The intraclass correlation coefficients of VRLN were calculated to evaluate intraobserver and interobserver reproducibility. The C-index was computed to examine the prognostic value of VRLN. P-value <0.05 were considered statistically significant. RESULTS: Participants were followed for a median of 26 months. VRLN, age, LV end-systolic volume index, and global longitudinal strain remained significantly associated with MACE in the multivariable model. Adding VRLN to a baseline model containing clinical and conventional cardiac MRI parameters significantly improved the accuracy of the predictive model (C-index of the baseline model: 0.781 vs. the model added VRLN: 0.814). DATA CONCLUSION: VRLN is a novel marker for risk stratification toward MACE in patients with ESRD, superior to native T1 mapping and LV ejection fraction. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY STAGE: 2.

An efficient context-aware approach for whole-slide image classification.

Computational pathology for gigapixel whole-slide images (WSIs) at slide level is helpful in disease diagnosis and remains challenging. We propose a context-aware approach termed WSI inspection via transformer (WIT) for slide-level classification via holistically modeling dependencies among patches on WSI. WIT automatically learns feature representation of WSI by aggregating features of all image patches. We evaluate classification performance of WIT and state-of-the-art baseline method. WIT achieved an accuracy of 82.1% (95% CI, 80.7%-83.3%) in the detection of 32 cancer types on the TCGA dataset, 0.918 (0.910-0.925) in diagnosis of cancer on the CPTAC dataset, and 0.882 (0.87-0.890) in the diagnosis of prostate cancer from needle biopsy slide, outperforming the baseline by 31.6%, 5.4%, and 9.3%, respectively. WIT can pinpoint the WSI regions that are most influential for its decision. WIT represents a new paradigm for computational pathology, facilitating the development of digital pathology tools.

Exogenous Nucleotides Ameliorate Age-Related Decline in Testosterone in Male Senescence-Accelerated Mouse Prone-8 (SAMP8) Mice by Modulating the Local Renin-Angiotensin System Antioxidant Pathway.

In older men, an age-related decline in testosterone is closely associated with various adverse health outcomes. With the progression of aging, hyperactivation of the local renin-angiotensin system (RAS) and oxidative stress increase in the testis. The regulation of RAS antioxidants may be a target to delay testicular aging and maintain testosterone levels. Exogenous nucleotides (NTs) have anti-aging potential in several systems, but there are no studies of their effects on the reproductive system. In our study, we examined the effects of exogenous NTs on testosterone synthesis and explored possible mechanisms of action. Therefore, senescence-accelerated mouse prone-8 (SAMP8) mice and senescence-accelerated mouse resistant 1 (SAMR1) were used in the experiment, and they were randomly divided into an NTs free group (NTs-F), a normal control group (control), a low-dose NTs group (NTs-L), a middle-dose NTs (NTs-M), a high-dose NTs group (NTs-H) and SAMR1 groups, and the testis of the mice were collected for testing after 9 months of intervention. The results showed that exogenous NTs could increase the testicular organ index in mice during aging, and delayed the age-associated decline in testosterone levels in SAMP8 male mice, possibly by modulating the local RAS antioxidant pathway and reducing oxidative stress to protect the testis. The present study provides new research clues for the development of preventive and therapeutic strategies for related diseases.

Attention distraction with gradient sharpening for multi-task adversarial attack.

The advancement of deep learning has resulted in significant improvements on various visual tasks. However, deep neural networks (DNNs) have been found to be vulnerable to well-designed adversarial examples, which can easily deceive DNNs by adding visually imperceptible perturbations to original clean data. Prior research on adversarial attack methods mainly focused on single-task settings, i.e., generating adversarial examples to fool networks with a specific task. However, real-world artificial intelligence systems often require solving multiple tasks simultaneously. In such multi-task situations, the single-task adversarial attacks will have poor attack performance on the unrelated tasks. To address this issue, the generation of multi-task adversarial examples should leverage the generalization knowledge among multiple tasks and reduce the impact of task-specific information during the generation process. In this study, we propose a multi-task adversarial attack method to generate adversarial examples from a multi-task learning network by applying attention distraction with gradient sharpening. Specifically, we first attack the attention heat maps, which contain more generalization information than feature representations, by distracting the attention on the attack regions. Additionally, we use gradient-based adversarial example-generating schemes and propose to sharpen the gradients so that the gradients with multi-task information rather than only task-specific information can make a greater impact. Experimental results on the NYUD-V2 and PASCAL datasets demonstrate that the proposed method can improve the generalization ability of adversarial examples among multiple tasks and achieve better attack performance.

Fractal analysis: Left ventricular trabecular complexity cardiac MRI adds independent risks for heart failure with preserved ejection fraction in participants with end-stage renal disease.

PURPOSE: To measure left ventricular (LV) trabecular complexity by fractal dimension (FD) in patients with end-stage renal disease (ESRD), and assess whether FD was an independent risk factor for heart failure with preserved ejection fraction (HFpEF), or a significant predictor for adverse outcome in this population. METHODS: The study retrospectively enrolled 104 participants with ESRD who underwent 3.0 T cardiac magnetic resonance imaging (MRI) from June 2018 to November 2020. LV trabeculation was quantified with fractal analysis of short-axis cine slices to estimate the FD. Logistic regression analyses were used to evaluate FD and cardiac MRI parameters and to find independent risk predictors. Cox proportional hazard regression was used to investigate the association between FD and MACE. RESULTS: LV FD was higher in in the HFpEF group than those in the non-HFpEF group, with the greatest difference near the base of the ventricle. Age, minimum left atrial volume index, and LV mean basal FD were independent predictors for HFpEF in patients with ESRD. Combining the mean basal FD with typical predictive factors resulted in a C-index (0.902 vs 0.921), which was not significantly higher. Same improvements were found for net reclassification improvement [0.642; 95% confidence interval (CI), 0.254-1.029] and integrated discrimination index (0.026; 95% CI, 0.008-0.061). Participants with a LV global FD above the cutoff value (1.278) had higher risks of MACE in ESRD patients. CONCLUSIONS: LV trabecular complexity measured by FD was an independent risk factor for HFpEF, and a significant predictor for MACE among patients with ESRD.

Contribution of Direct Cerebral Vascular Transport in Brain Substance Clearance.

The accumulation of harmful substances has long been recognized as a likely cause of many neurodegenerative diseases. The two classic brain clearance pathways are cerebrospinal fluid (CSF) and vascular circulation systems. Since the discovery of the glymphatic system, research on the CSF pathway has gained momentum, and impaired CSF clearance has been implicated in virtually all neurodegenerative animal models. However, the contribution of the direct participation of vascular transport across the blood-brain barrier in clearing substances is often ignored in glymphatic papers. Supportive evidence for the direct involvement of parenchymal vasculature in substance clearance is accumulated. First, multiple mechanisms have been proposed for the vascular drainage of exogenous and endogenous substances across the blood-brain barriers. Second, the "traditional" role of arachnoid villi and granulations as the main site for CSF draining into the vasculature system has been questioned. Third, MRI studies using different CSF tracers indicate that parenchymal vasculature directly participates in tracer efflux, consistent with immunohistochemical findings. Here we will review evidence in the literature that supports the direct participation of the parenchymal vascular system in substance clearance, in addition to the CSF clearance pathways.

Abscisic acid (ABA) alleviates cadmium toxicity by enhancing the adsorption of cadmium to root cell walls and inducing antioxidant defense system of Cosmos bipinnatus.

Cadmium (Cd) pollution is a global problem affecting soil ecology and plant growth. Abscisic acid (ABA) acts as a growth and stress hormone, regulates cell wall synthesis, and plays an important role in plant responses to stress. There are few studies on the mechanisms behind abscisic acid alleviation of cadmium stress in Cosmos bipinnatus, especially in regards to regulation of the root cell wall. This study examined the effects of different concentrations of abscisic acid at different concentrations of cadmium stress. Through adding 5 µmol/L and 30 µmol/L cadmium, followed by spraying 10 µmol/L and 40 µmol/L ABA in a hydroponic experiment, it was found that under two concentrations of cadmium stress, low concentration of ABA improved root cell wall polysaccharide, Cd, and uronic acid content. Especially in pectin, after the application of low concentration ABA, the cadmium concentration was significantly increased by 1.5 times and 1.2 times compared with the Cd concentration under Cd5 and Cd30 treatment alone, respectively. Fourier-Transform Infrared spectroscopy (FTIR) demonstrated that cell wall functional groups such as -OH and -COOH were increased with exposure to ABA. Additionally, the exogenous ABA also increased expression of three kinds of antioxidant enzymes and plant antioxidants. The results of this study suggest that ABA could reduce Cd stress by increasing Cd accumulation, promoting Cd adsorption on the root cell wall, and activating protective mechanisms. This result could help promote application of C. bipinnatus for phytostabilization of cadmium-contaminated soil.

A deep learning method for the automated assessment of paradoxical pulsation after myocardial infarction using multicenter cardiac MRI data.

OBJECTIVE: The current study aimed to explore a deep convolutional neural network (DCNN) model that integrates multidimensional CMR data to accurately identify LV paradoxical pulsation after reperfusion by primary percutaneous coronary intervention with isolated anterior infarction. METHODS: A total of 401 participants (311 patients and 90 age-matched volunteers) were recruited for this prospective study. The two-dimensional UNet segmentation model of the LV and classification model for identifying paradoxical pulsation were established using the DCNN model. Features of 2- and 3-chamber images were extracted with 2-dimensional (2D) and 3D ResNets with masks generated by a segmentation model. Next, the accuracy of the segmentation model was evaluated using the Dice score and classification model by receiver operating characteristic (ROC) curve and confusion matrix. The areas under the ROC curve (AUCs) of the physicians in training and DCNN models were compared using the DeLong method. RESULTS: The DCNN model showed that the AUCs for the detection of paradoxical pulsation were 0.97, 0.91, and 0.83 in the training, internal, and external testing cohorts, respectively (p < 0.001). The 2.5-dimensional model established using the end-systolic and end-diastolic images combined with 2-chamber and 3-chamber images was more efficient than the 3D model. The discrimination performance of the DCNN model was better than that of physicians in training (p < 0.05). CONCLUSIONS: Compared to the model trained by 2-chamber or 3-chamber images alone or 3D multiview, our 2.5D multiview model can combine the information of 2-chamber and 3-chamber more efficiently and obtain the highest diagnostic sensitivity. CLINICAL RELEVANCE STATEMENT: A deep convolutional neural network model that integrates 2-chamber and 3-chamber CMR images can identify LV paradoxical pulsation which correlates with LV thrombosis, heart failure, ventricular tachycardia after reperfusion by primary percutaneous coronary intervention with isolated anterior infarction. KEY POINTS: • The epicardial segmentation model was established using the 2D UNet based on end-diastole 2- and 3-chamber cine images. • The DCNN model proposed in this study had better performance for discriminating LV paradoxical pulsation accurately and objectively using CMR cine images after anterior AMI compared to the diagnosis of physicians in training. • The 2.5-dimensional multiview model combined the information of 2- and 3-chamber efficiently and obtained the highest diagnostic sensitivity.

Post-COVID symptom profiles and duration in a global convalescent COVID-19 observational cohort: Correlations with demographics, medical history, acute COVID-19 severity and global region.

Background: Post-COVID conditions are characterised by persistent symptoms that negatively impact quality of life after SARS-CoV-2 diagnosis. While post-COVID risk factors and symptoms have been extensively described in localised regions, especially in the global north, post-COVID conditions remain poorly understood globally. The global, observational cohort study HVTN 405/HPTN 1901 characterises the convalescent course of SARS-CoV-2 infection among adults in North and South America and Africa. Methods: We categorised the cohort by infection severity (asymptomatic, symptomatic, no oxygen requirement (NOR), non-invasive oxygen requirement (NIOR), invasive oxygen requirement (IOR)). We applied a regression model to assess correlations of demographics, co-morbidities, disease severity, and concomitant medications with COVID-19 symptom persistence and duration across global regions. Results: We enrolled 759 participants from Botswana, Malawi, South Africa, Zambia, Zimbabwe, Peru, and the USA a median of 51 (interquartile range (IQR) = 35-66) days post-diagnosis, from May 2020 to March 2021. 53.8% were female, 69.8% were 18-55 years old (median (md) = 44 years old, IQR = 33-58). Comorbidities included obesity (42.8%), hypertension (24%), diabetes (14%), human immunodeficiency virus (HIV) infection (11.6%) and lung disease (7.5%). 76.2% were symptomatic (NOR = 47.4%; NIOR = 22.9%; IOR = 5.8%). Median COVID-19 duration among symptomatic participants was 20 days (IQR = 11-35); 43.4% reported symptoms after COVID-19 resolution, 33.6% reported symptoms ≥30 days, 9.9% reported symptoms ≥60 days. Symptom duration correlated with disease severity (P < 0.001, NIOR vs NOR; P = 0.003, IOR vs NOR), lung disease (P = 0.001), race (P < 0.05, non-Hispanic Black vs White), and global region (P < 0.001). Prolonged viral shedding correlated with persistent abdominal pain (odds ratio (OR) = 5.51, P < 0.05) and persistent diarrhoea (OR = 6.64, P < 0.01). Conclusions: Post-COVID duration varied with infection severity, race, lung disease, and region. Better understanding post-COVID conditions, including regionally-diverse symptom profiles, may improve clinical assessment and management globally. Registration: Clinicaltrials.gov (#NCT04403880).

Exogenous Nucleotides Ameliorate Ageing-Related Intestinal Inflammation in Senescence-Accelerated Mouse Prone-8 (SAMP8) Mice.

As one of the most important barriers in the body, the intestinal barrier is a key factor in maintaining human health. Ageing of the intestine is a degenerative process that is closely associated with a variety of poor health conditions in the elderly. Inflammation and the immune system are anti-ageing targets that can regulate the function of the intestine. Nucleotides (NTs) are involved in important physiological and biochemical reactions in the body, but there are few studies about their effect on the ageing intestine. This paper examines the role of exogenous NTs in the ageing intestine. For this purpose, we used senescence-accelerated mouse prone-8 (SAMP8) mice and senescence-accelerated mouse resistant 1 (SAMR1) mice for the experiment, and randomly divided the mice into NTs-free, Normal Control, NTs-low, NTs-medium, NTs-high, and SAMR1 groups. After 9 months of intervention, we collected the colon tissue of mice for testing. In our study, exogenous NTs could increase bodyweight of mice during ageing and improve the morphological structure of the intestine, and we found that NTs could promote the secretion of intestinal protective factors, such as TFF3 and TE. Furthermore, supplementation with NTs suppressed intestinal inflammation and improved intestinal immunity, possibly by activating the p38 signaling pathway. These results suggest that exogenous NTs are able to maintain the health condition of the ageing intestine.

A Novel Intraoperative Leak Test Procedure (GAM Procedure) to Prevent Postoperative Anastomotic Leakage in Gastric Cancer Patients Who Underwent Gastrectomy.

BACKGROUND: Anastomotic leakage following a radical gastrectomy is a serious complication of gastric cancer and esophagogastric junction cancer. The benefit of intraoperative leak testing for the prevention of postoperative anastomotic leakage has been controversial. We introduce a new procedure, which combines the techniques of gastroscopy, air, and methylene blue (GAM) for intraoperative leakage testing. Our objective was to evaluate the efficacy and safety of the GAM procedure for intraoperative leak testing and to compare the surgical complications of gastric cancer patients who underwent gastrectomy with and without intraoperative leak testing using the GAM procedure. MATERIALS AND METHODS: A total of 210 patients who underwent radical gastrectomy for gastric cancer were included. Patients were divided into 2 groups: the intraoperative leak testing group using the GAM procedure (IOLT), and the group for which no intraoperative leak testing was done (NIOLT). Clinical and pathologic characteristics, the incidence of postoperative anastomotic leakage, and other surgical complications were compared between the 2 groups. RESULTS: There were 82 patients in the IOLT group and 82 patients in the NIOLT group after propensity score matching. In the IOLT group, 4 (4.9%) patients were found to have anastomotic discontinuity during the operation; we repaired these anastomotic discontinuities intraoperatively. The incidence of postoperative anastomotic leakage was higher in the NIOLT group compared with the IOLT group, 6 (7.3%) versus 0 (0%), respectively ( P =0.01). The average time of the GAM procedure was 4.99±1.75 minutes. The surgical time was prolonged by 30 minutes in the IOLT group compared with the NIOLT group, 302.2±79.9 versus 272.1±85.2, respectively ( P =0.02). The length of hospital stay, 15.80±4.55 versus 17.00±6.20 ( P =0.16) was reduced in the IOLT group compared with the NIOLT group. The logistic regression model suggested that IOLT, sex, age, Eastern Cooperative Oncology Group, cT stage, tumor diameter, pT stage, pN stage, and Lauren classification were not risk factors for postoperative complication. CONCLUSIONS: The GAM procedure of intraoperative leakage testing can effectively reduce the incidence of postoperative anastomotic leakage in gastric cancer patients undergoing gastrectomy.

Generative pretraining from large-scale transcriptomes for single-cell deciphering.

Exponential accumulation of single-cell transcriptomes poses great challenge for efficient assimilation. Here, we present an approach entitled generative pretraining from transcriptomes (tGPT) for learning feature representation of transcriptomes. tGPT is conceptually simple in that it autoregressive models the ranking of a gene in the context of its preceding neighbors. We developed tGPT with 22.3 million single-cell transcriptomes and used four single-cell datasets to evalutate its performance on single-cell analysis tasks. In addition, we examine its applications on bulk tissues. The single-cell clusters and cell lineage trajectories derived from tGPT are highly aligned with known cell labels and states. The feature patterns of tumor bulk tissues learned by tGPT are associated with a wide range of genomic alteration events, prognosis, and treatment outcome of immunotherapy. tGPT represents a new analytical paradigm for integrating and deciphering massive amounts of transcriptome data and it will facilitate the interpretation and clinical translation of single-cell transcriptomes.