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Triple-negative breast cancer (TNBC) is a heterogeneous disease and lacks effective treatment. Our previous study classified TNBCs into four subtypes with putative therapeutic targets. Here, we report the final results of FUTURE, a phase II umbrella trial designed to explore whether the subtyping-based strategy may improve the outcomes in metastatic TNBC patients. A total of 141 patients with a median of three previous lines of therapies in the metastatic setting were enrolled in seven parallel arms. Confirmed objective responses were achieved in 42 patients (29.8%; 95% confidence interval [CI], 22.4–38.1). The median values of progression-free survival and overall survival were 3.4 (95% CI: 2.7–4.2) and 10.7 (95% CI: 9.1–12.3) months, respectively. Given Bayesian predictive probability, efficacy boundaries were achieved in four arms. Furthermore, integrated genomic and clinicopathological profiling illustrated associations of clinical and genomic parameters with treatment efficacy, and the efficacy of novel antibody–drug conjugates was explored in preclinical TNBC models of subtypes for which treatment was futile. In general, the FUTURE strategy recruits patients efficiently and provides promising efficacy with manageable toxicities, outlining a direction for further clinical exploration.

In recent decades, the demand for vegetables has increased significantly due to the blooming global population. Climate change has affected vegetable production by increasing the frequencies and severity of abiotic and biotic stresses. Among the abiotic stresses, drought and salinity are the major issues that possess severe threats on vegetable production. Many vegetables (e.g., carrot, tomato, okra, pea, eggplant, lettuce, potato) are usually sensitive to drought and salt stress. The defence mechanisms of plants against salt and drought stress have been extensively studied in model plant species and field crops. Better understanding of the mechanisms of susceptibility of vegetables to drought and salt stresses will help towards the development of more tolerant genotypes as a long-term strategy against these stresses. However, the intensity of the challenges also warrants more immediate approaches to mitigate these stresses and enhance vegetable production in the short term. Therefore, this review enlightens the updated knowledge of responses (physiological and molecular) against drought and salinity in vegetables and potentially effective strategies to enhance production. Moreover, we summarized different technologies such as seed priming, genetic transformation, biostimulants, nanotechnology, and cultural practices adopted to enhance vegetable production under drought and salinity stress. We propose that approaches of conventional breeding, genetic engineering, and crop management should be combined to generate drought and salt resistance cultivars and adopt smart cultivation practices for sustainable vegetable production in a changing climate.

Background This Bayesian network analysis was performed to assess the effects of different intravenous sedatives on outcomes in adult critically ill patients. Methods We searched for and gathered data from MEDLINE, Cochrane Central Register of Controlled Trials, Elsevier and Web of Science databases. Bayesian network analysis was performed to evaluate the effect of different intravenous sedatives on outcome in adult critically ill patients. Random errors were evaluated by trial sequential analysis (TSA). Results Twenty-seven studies including 8,599 critically ill adult patients were enrolled in the analysis. Comparisons among lorazepam, midazolam, propofol, dexmedetomidine, haloperidol and placebo or usual care were presented in a network plot. No significant differences were found for longest mortality in critically ill patients. However, when compared with midazolam, dexmedetomidine had a shorter ICU length of stay and a lower incidence of delirium. Meanwhile, midazolam had a longer ICU length of stay when compared with placebo, propofol and usual care. Subgroup analyses were performed respectively in sepsis, invasive ventilated patients and postoperative patients, as well as patients with higher severity of disease. Lower mortality was found in dexmedetomidine group when compared with placebo in postoperative patients. No differences were found for mortality, ICU length of stay and incidence of delirium in other subgroups. When compared with other sedatives, dexmedetomidine shortened ICU length of stay significantly in ventilated patients. TSA indicated lack of firm evidence for a beneficial effect. Conclusions No differences were found for longest mortality of different sedatives in adult critically ill patients. However, when compared with midazolam, dexmedetomidine had a shorter ICU length of stay and a lower incidence of delirium. TSA indicated lack of firm evidence for the results. More powered, randomized, controlled trials are needed to determine the effects.

This study investigated the composition of pathogenic microorganisms, clinical features, and therapeutic strategies of infective artery rupture of renal allografts in recipients receiving deceased donor (DD) kidneys.We retrospectively studied the clinical data of the DD kidney transplant recipients with donor-associated infection at Tongji Hospital, Wuhan, China from January 1, 2015 to December 31, 2018, related recipients and corresponding donors. We collected the entire results of pathogenic microorganisms cultured from these related ruptured kidneys and then analyzed their distribution and differences.A total of 1440 kidney transplants from DD were performed in our center. The total incidence of infective artery rupture in kidney transplants was about 0.76% (11/1440), and the annual incidence ranged from 0.25% to 1.03%. The microbial culture results revealed that 11 recipients suffered from infective artery rupture and 3 recipients who accepted the kidney from same donor had the donor-associated pathogens, including 9 fungal strains (28.1%) and 23 bacterial strains (71.9%). There were 4 recipients infected with multi-drug-resistant Staphylococcus and Klebsiella pneumoniae from the above 11 recipients, of which, 10 recipients underwent graft loss, and one died of septic shock. The microbial cultures of the remaining 3 recipients who received appropriate anti-infective regimens turned negative eventually, and the patients were discharged successfully without significant complications.Renal recipients with infections derived from DDs were at high risk of artery rupture, graft loss, or even death. Appropriate anti-infective treatment is essential to reduce the incidence of artery rupture and mortality.

Background Pediatric sepsis is a complicated condition characterized by life-threatening organ failure resulting from a dysregulated host response to infection in children. It is associated with high rates of morbidity and mortality, and rapid detection and administration of antimicrobials have been emphasized. The objective of this study was to evaluate the diagnostic biomarkers of pediatric sepsis and the function of immune cell infiltration in the development of this illness. Methods Three gene expression datasets were available from the Gene Expression Omnibus collection. First, the differentially expressed genes (DEGs) were found with the use of the R program, and then gene set enrichment analysis was carried out. Subsequently, the DEGs were combined with the major module genes chosen using the weighted gene co-expression network. The hub genes were identified by the use of three machine-learning algorithms: random forest, support vector machine-recursive feature elimination, and least absolute shrinkage and selection operator. The receiver operating characteristic curve and nomogram model were used to verify the discrimination and efficacy of the hub genes. In addition, the inflammatory and immune status of pediatric sepsis was assessed using cell-type identification by estimating relative subsets of RNA transcripts (CIBERSORT). The relationship between the diagnostic markers and infiltrating immune cells was further studied. Results Overall, after overlapping key module genes and DEGs, we detected 402 overlapping genes. As pediatric sepsis diagnostic indicators, CYSTM1 (AUC = 0.988), MMP8 (AUC = 0.973), and CD177 (AUC = 0.986) were investigated and demonstrated statistically significant differences (P Conclusions The candidate hub genes (CD177, CYSTM1, and MMP8) were identified, and the nomogram was constructed for pediatric sepsis diagnosis. Our study could provide potential peripheral blood diagnostic candidate genes for pediatric sepsis patients.