As resident macrophages of the central nervous system (CNS), microglia are associated with diverse functions essential to the developing and adult brain during homeostasis and disease. They are aided ...in their tasks by intricate bidirectional communication with other brain cells under steady-state conditions as well as with infiltrating peripheral immune cells during perturbations. Harmonious cell-cell communication involving microglia are considered crucial to maintain the healthy state of the tissue environment and to overcome pathology such as neuroinflammation. Analyses of such intercellular pathways have contributed to our understanding of the heterogeneous but context-associated microglial responses to environmental cues across neuropathology, including inflammatory conditions such as infections and autoimmunity, as well as immunosuppressive states as seen in brain tumors. Here, we summarize the latest evidence demonstrating how these interactions drive microglia immune and non-immune functions, which coordinate the transition from homeostatic to disease-related cellular states.
Understanding the diverse microglial interactions and functions taking place across neuropathology will pave the way to future treatment strategies. Borst, Dumas, and Prinz summarize our current understanding of microglial interactions with central nervous system (CNS)-resident and CNS-infiltrating cells during homeostasis and disease and highlight how this communication drives their immune and non-immune functions.
One-fourth of colorectal neoplasia are missed at screening colonoscopy, representing the main cause of interval colorectal cancer. Deep learning systems with real-time computer-aided polyp detection ...(CADe) showed high accuracy in artificial settings, and preliminary randomized controlled trials (RCTs) reported favorable outcomes in the clinical setting. The aim of this meta-analysis was to summarize available RCTs on the performance of CADe systems in colorectal neoplasia detection.
We searched MEDLINE, EMBASE, and Cochrane Central databases until March 2020 for RCTs reporting diagnostic accuracy of CADe systems in the detection of colorectal neoplasia. The primary outcome was pooled adenoma detection rate (ADR), and secondary outcomes were adenoma per colonoscopy (APC) according to size, morphology, and location; advanced APC; polyp detection rate; polyps per colonoscopy; and sessile serrated lesions per colonoscopy. We calculated risk ratios (RRs), performed subgroup and sensitivity analyses, and assessed heterogeneity and publication bias.
Overall, 5 randomized controlled trials (4354 patients) were included in the final analysis. Pooled ADR was significantly higher in the CADe group than in the control group (791/2163 36.6% vs 558/2191 25.2%; RR, 1.44; 95% confidence interval CI, 1.27-1.62; P < .01; I2 = 42%). APC was also higher in the CADe group compared with control (1249/2163 .58 vs 779/2191 .36; RR, 1.70; 95% CI, 1.53-1.89; P < .01; I2 = 33%). APC was higher for ≤5-mm (RR, 1.69; 95% CI, 1.48-1.84), 6- to 9-mm (RR, 1.44; 95% CI, 1.19-1.75), and ≥10-mm adenomas (RR, 1.46; 95% CI, 1.04-2.06) and for proximal (RR, 1.59; 95% CI, 1.34-1.88), distal (RR, 1.68; 95% CI, 1.50-1.88), flat (RR, 1.78; 95% CI, 1.47-2.15), and polypoid morphology (RR, 1.54; 95% CI, 1.40-1.68). Regarding histology, CADe resulted in a higher sessile serrated lesion per colonoscopy (RR, 1.52; 95% CI, 1.14-2.02), whereas a nonsignificant trend for advanced ADR was found (RR, 1.35; 95% CI, .74-2.47; P = .33; I2 = 69%). Level of evidence for RCTs was graded as moderate.
According to available evidence, the incorporation of artificial intelligence as aid for detection of colorectal neoplasia results in a significant increase in the detection of colorectal neoplasia, and such effect is independent from main adenoma characteristics.
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Growth–defense trade-offs in plants He, Zuhua; Webster, Shanice; He, Sheng Yang
CB/Current biology,
06/2022, Letnik:
32, Številka:
12
Journal Article
Recenzirano
Odprti dostop
Walking through a garden or a crop field, you may notice that plants damaged by pests (insects or pathogens) look smaller than the same kind of plants nearby that are not damaged. An obvious ...explanation would be that damaged plants may have lost substantial photosynthetic tissue due to insect and pathogen activities. As such, plants may have a reduced ability to capture light and perform photosynthesis, which fuels the growth of plants. While this is likely part of the reason why damaged plants look smaller, there is also another and perhaps more fascinating explanation that we would like to discuss here in this primer. It turns out that plants attacked by insects, pathogens and other biotic stressors may ‘purposely’ slow down their growth and that this response is often systemic, meaning that it occurs throughout the plant and beyond the tissue that is damaged by pests. Interestingly, some chemicals or plant genetic mutations that simulate insect or pathogen attacks without causing a loss of photosynthetic tissue can also slow plant growth, suggesting the physical loss of photosynthetic tissue per se is not always a prerequisite for slowing down plant growth. In contrast, there are conditions under which plants need to grow rapidly. For example, plants grow quickly when searching for light during germination or under a shaded canopy due to crowding from neighboring plants. Under these conditions, rapid plant growth is often accompanied by increased susceptibility to pests, presumably because growth is prioritized over defense. This inverse growth–defense relationship is commonly known as the ‘growth–defense trade-off’ and may be considered one of the most fundamental principles of ‘plant economics’ that allows plants to adjust growth and defense based on external conditions (Figure 1). As plants must both grow and defend in order to reproduce and survive in the natural world, growth–defense trade-offs have important ecological consequences. In agricultural settings, crops have often been bred to maximize growth-related traits, which could inadvertently result in the loss of useful genetic traits for biotic defenses. Thus, deciphering the molecular mechanisms underlying growth–defense trade-off phenomena could impact future crop breeding strategies aimed at designing superior crop plants with high yields as well as the ability to defend against biotic stressors. Here, we discuss some of the prevailing hypotheses about growth–defense trade-offs, our current understanding of the underlying mechanisms, and the ongoing efforts to optimize growth–defense trade-offs in crop plants.
He et al. summarize hypotheses and molecular mechanisms behind trade-offs in plant growth and defense and describe how these have been exploited for crop improvement.
Effective treatments for patients with cholangiocarcinoma after progression on gemcitabine-based chemotherapy are urgently needed. Mutations in the BRAF gene have been found in 5% of biliary tract ...tumours. The combination of dabrafenib and trametinib has shown activity in several BRAFV600E-mutated cancers. We aimed to assess the activity and safety of dabrafenib and trametinib combination therapy in patients with BRAFV600E-mutated biliary tract cancer.
This study is part of an ongoing, phase 2, open-label, single-arm, multicentre, Rare Oncology Agnostic Research (ROAR) basket trial in patients with BRAFV600E-mutated rare cancers. Patients were eligible for the biliary tract cancer cohort if they were aged 18 years or older, had BRAFV600E-mutated, unresectable, metastatic, locally advanced, or recurrent biliary tract cancer, an Eastern Cooperative Oncology Group performance status of 0–2, and had received previous systemic treatment. All patients were treated with oral dabrafenib 150 mg twice daily and oral trametinib 2 mg once daily until disease progression or intolerance of treatment. The primary endpoint was the overall response rate, which was determined by Response Evaluation Criteria in Solid Tumors version 1.1 in the intention-to-treat evaluable population, which comprised all enrolled patients regardless of receiving treatment who were evaluable (ie, had progression, began a new anticancer treatment, withdrew consent, died, had stable disease for 6 weeks or longer, or had two or more post-baseline assessments). The ROAR trial is registered with ClinicalTrials.gov, NCT02034110. These results are based on an interim analysis; the study is active but not recruiting.
Between March 12, 2014, and July 18, 2018, 43 patients with BRAFV600E-mutated biliary tract cancer were enrolled to the study and were evaluable. Median follow-up was 10 months (IQR 6–15). An investigator-assessed overall response was achieved by 22 (51%, 95% CI 36–67) of 43 patients. An independent reviewer-assessed overall response was achieved by 20 (47%, 95% CI 31–62) of 43 patients. The most common grade 3 or worse adverse event was increased γ-glutamyltransferase in five (12%) patients. 17 (40%) patients had serious adverse events and nine (21%) had treatment-related serious adverse events, the most frequent of which was pyrexia (eight 19%). No treatment-related deaths were reported.
Dabrafenib plus trametinib combination treatment showed promising activity in patients with BRAFV600E-mutated biliary tract cancer, with a manageable safety profile. Routine testing for BRAFV600E mutations should be considered in patients with biliary tract cancer.
GlaxoSmithKline and Novartis.
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