High expression of IFNβ1 (CAFs) or MX1 (tumour cells) correlated with reduced survival after chemotherapy, especially in claudin-low tumours (which MDA-MB-231 and MDA-MB-157 cells represent). Antibodies that block IFN receptors reduced CAF-dependent chemoprotection.

CAF-induced activation of IFN signalling in claudin-low TNBCs results in chemoresistance. Inhibition of this pathway represents a novel method to improve breast cancer outcomes.

CAF-induced activation of IFN signalling in claudin-low TNBCs results in chemoresistance. Inhibition of this pathway represents a novel method to improve breast cancer outcomes.

Patients with refractory colorectal (CRC) cancer have few treatment options. This trial tests the combination of metformin and irinotecan in this setting.

A phase 2 single-arm trial was conducted, patients received metformin 2500 mg orally a day plus irinotecan 125 mg/m

intravenously weekly D1 and D8 every 21 days. The primary endpoint was the disease control rate according to the Response Evaluation Criteria in Solid Tumors version 1.1 at 12 weeks.

Between December 2015 and January 2018, 41 patients were enrolled. Seventeen patients (41%) met the primary endpoint of disease control in 12 weeks; hence, the study was deemed positive. The median progression-free survival was 3.3 months (CI 95%, 2.0-4.5 months), and the median overall survival was 8.4 months (CI 95%, 5.9-10.8 months). Both mutation RAS status and disease control at 12 weeks impacted overall survival in the multivariate model (HR 2.28, CI 95%, 1.12-4.7, p = 0.02; and HR 0.21, CI 95%, 0.08-0.5, p = 0.001, respectively). The most common adverse event was diarrhoea (29.2% grade 3).

In this trial, metformin plus irinotecan demonstrated disease control in patients with refractory CRC. Further trials with optimised diarrhoea control are needed to confirm these results.

In this trial, metformin plus irinotecan demonstrated disease control in patients with refractory CRC. Further trials with optimised diarrhoea control are needed to confirm these results.Rapid 3D imaging of entire organs and organisms at cellular resolution is a recurring challenge in life science. Here we report on a computational light-sheet microscopy able to achieve minute-timescale high-resolution mapping of entire macro-scale organs. Through combining a dual-side confocally-scanned Bessel light-sheet illumination which provides thinner-and-wider optical sectioning of deep tissues, with a content-aware compressed sensing (CACS) computation pipeline which further improves the contrast and resolution based on a single acquisition, our approach yields 3D images with high, isotropic spatial resolution and rapid acquisition over two-order-of-magnitude faster than conventional 3D microscopy implementations. We demonstrate the imaging of whole brain (~400 mm3), entire gastrocnemius and tibialis muscles (~200 mm3) of mouse at ultra-high throughput of 5~10 min per sample and post-improved subcellular resolution of ~ 1.5 μm (0.5-μm iso-voxel size). ML-SI3 cost Various system-level cellular analyses, such as mapping cell populations at different brain sub-regions, tracing long-distance projection neurons over the entire brain, and calculating neuromuscular junction occupancy across whole muscle, are also readily accomplished by our method.The diversity reflected by >100 different neural cell types fundamentally contributes to brain function and a central idea is that neuronal identity can be inferred from genetic information. Recent large-scale transcriptomic assays seem to confirm this hypothesis, but a lack of morphological information has limited the identification of several known cell types. In this study, we used single-cell RNA-seq in morphologically identified parvalbumin interneurons (PV-INs), and studied their transcriptomic states in the morphological, physiological, and developmental domains. Overall, we find high transcriptomic similarity among PV-INs, with few genes showing divergent expression between morphologically different types. Furthermore, PV-INs show a uniform synaptic cell adhesion molecule (CAM) profile, suggesting that CAM expression in mature PV cells does not reflect wiring specificity after development. Together, our results suggest that while PV-INs differ in anatomy and in vivo activity, their continuous transcriptomic and homogenous biophysical landscapes are not predictive of these distinct identities.

Due to selection bias and other issues, the only available serum bilirubin-based nomogram does not reflect the natural history of early neonatal bilirubinemia. Our objective was to obtain a global picture of the natural history of early post-natal bilirubin trajectories.

We pooled readings from 19 published transcutaneous bilirubin nomogram reports including many newborns at multiple sites. We constructed a universal transcutaneous bilirubin nomogram which included the 25th, 50th, 75th, and 95th percentiles from 12 to 120 h.

The global transcutaneous bilirubin nomogram included >119,000 readings from 44,392 apparently normal, predominantly breastfed newborns ≥35 weeks gestation. The pooled transcutaneous bilirubin trajectories increased during the first 3 post-natal days, and peaked or plateaued between the 3rd and 4th days.

We provide the first globally derived transcutaneous bilirubin nomogram that reflects the natural history of early neonatal bilirubinemia in neonates ≥35 weeks gestation.

We provide the first globally derived transcutaneous bilirubin nomogram that reflects the natural history of early neonatal bilirubinemia in neonates ≥35 weeks gestation.Quality improvement (QI) is a relatively new and evolving field as it applies to healthcare. Hence, publishing a QI paper may present certain challenges as QI differs from standard types of scientific research. Some considerations in writing are inherent to all types of manuscripts submitted for publication, whereas others are unique to QI papers. This paper, the final in a series of eight papers related to QI in the neonatal setting, describes the best practices for writing and publishing QI manuscripts. Common pitfalls to avoid are also highlighted.