Quantum oscillations in the hole-doped cuprates and the confinement of spinons.

A long-standing problem in the study of the under-hole-doped cuprates has been the description of the Fermi surfaces underlying the high magnetic field quantum oscillations, and their connection to the higher temperature pseudogap metal. Harrison and Sebastian [ , 226402 (2011)] proposed that the pseudogap "Fermi arcs" are reconstructed into an electron pocket by field-induced charge density wave order. But computations on such a model [Zhang and Mei, , 47008 (2016)] show an unobserved additional oscillation frequency from a Fermi surface arising from the backsides of the hole pockets completing the Fermi arcs.

Multi-omic lineage tracing predicts the transcriptional, epigenetic and genetic determinants of cancer evolution.

Cancer is a highly heterogeneous disease, where phenotypically distinct subpopulations coexist and can be primed to different fates. Both genetic and epigenetic factors may drive cancer evolution, however little is known about whether and how such a process is pre-encoded in cancer clones. Using single-cell multi-omic lineage tracing and phenotypic assays, we investigate the predictive features of either tumour initiation or drug tolerance within the same cancer population.

Large-sample evidence on the impact of unconventional oil and gas development on surface waters.

The impact of unconventional oil and gas development on water quality is a major environmental concern. We built a large geocoded database that combines surface water measurements with horizontally drilled wells stimulated by hydraulic fracturing (HF) for several shales to examine whether temporal and spatial well variation is associated with anomalous salt concentrations in United States watersheds. We analyzed four ions that could indicate water impact from unconventional development.

miR-146 connects stem cell identity with metabolism and pharmacological resistance in breast cancer.

Although ectopic overexpression of miRNAs can influence mammary normal and cancer stem cells (SCs/CSCs), their physiological relevance remains uncertain. Here, we show that miR-146 is relevant for SC/CSC activity. MiR-146a/b expression is high in SCs/CSCs from human/mouse primary mammary tissues, correlates with the basal-like breast cancer subtype, which typically has a high CSC content, and specifically distinguishes cells with SC/CSC identity.

A CNN-aided method to predict glaucoma progression using DARC (Detection of Apoptosing Retinal Cells).

Background: A key objective in glaucoma is to identify those at risk of rapid progression and blindness. Recently, a novel first-in-man method for visualising apoptotic retinal cells called DARC (Detection-of-Apoptosing-Retinal-Cells) was reported. The aim was to develop an automatic CNN-aided method of DARC spot detection to enable prediction of glaucoma progression.

Correction: Dual role for miR-34a in the control of early progenitor proliferation and commitment in the mammary gland and in breast cancer.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Delivery of biologically active miR-34a in normal and cancer mammary epithelial cells by synthetic nanoparticles.

Functional RNAs, such as microRNAs, are emerging as innovative tools in the treatment of aggressive and incurable cancers. In this study, we explore the potential of silica dioxide nanoparticles (SiONPs) in the delivery of biologically active miRNAs. Focusing on the tumor-suppressor miR-34a, we evaluated miRNAs delivery by SiONPs into the mammary gland, using in vitro as well as in vivo model systems.

p53 Loss in Breast Cancer Leads to Myc Activation, Increased Cell Plasticity, and Expression of a Mitotic Signature with Prognostic Value.

Loss of p53 function is invariably associated with cancer. Its role in tumor growth was recently linked to its effects on cancer stem cells (CSCs), although the underlying molecular mechanisms remain unknown. Here, we show that c-myc is a transcriptional target of p53 in mammary stem cells (MaSCs) and is activated in breast tumors as a consequence of p53 loss.

Dual role for miR-34a in the control of early progenitor proliferation and commitment in the mammary gland and in breast cancer.

The role of the tumour-suppressor miR-34 family in breast physiology and in mammary stem cells (MaSCs) is largely unknown. Here, we revealed that miR-34 family, and miR-34a in particular, is implicated in mammary epithelium homoeostasis. Expression of miR-34a occurs upon luminal commitment and differentiation and serves to inhibit the expansion of the pool of MaSCs and early progenitor cells, likely in a p53-independent fashion.

Insc:LGN tetramers promote asymmetric divisions of mammary stem cells.

Asymmetric cell divisions balance stem cell proliferation and differentiation to sustain tissue morphogenesis and homeostasis. During asymmetric divisions, fate determinants and niche contacts segregate unequally between daughters, but little is known on how this is achieved mechanistically. In Drosophila neuroblasts and murine mammary stem cells, the association of the spindle orientation protein LGN with the stem cell adaptor Inscuteable has been connected to asymmetry.

Can the optimal type of stent be predicted based on clinical risk factors? A subgroup analysis of the randomized BASKET-PROVE trial.

Background: The randomized BASKET-PROVE study showed no significant differences between sirolimus-eluting stents (SES), everolimus-eluting stents (EES), and bare-metal stents (BMS) with respect to the primary end point, rates of death from cardiac causes, or myocardial infarction (MI) at 2 years of follow-up, in patients requiring stenting of a large coronary artery. Clinical risk factors may affect clinical outcomes after percutaneous coronary interventions. We present a retrospective analysis of the BASKET-PROVE data addressing the question as to whether the optimal type of stent can be predicted based on a cumulative clinical risk score.

Degradation dynamics of microRNAs revealed by a novel pulse-chase approach.

The regulation of miRNAs is critical to the definition of cell identity and behavior in normal physiology and disease. To date, the dynamics of miRNA degradation and the mechanisms involved in remain largely obscure, in particular, in higher organisms. Here, we developed a pulse-chase approach based on metabolic RNA labeling to calculate miRNA decay rates at genome-wide scale in mammalian cells.

The BET Bromodomain Inhibitor OTX015 Affects Pathogenetic Pathways in Preclinical B-cell Tumor Models and Synergizes with Targeted Drugs.

Purpose: In cancer cells, the epigenome is often deregulated, and inhibition of the bromodomain and extra-terminal (BET) family of bromodomain-containing proteins is a novel epigenetic therapeutic approach. Preliminary results of an ongoing phase I trial have reported promising activity and tolerability with the new BET bromodomain inhibitor OTX015.

Experimental Design: We assessed the preclinical activity of OTX015 as single agent and in combination in mature B-cell lymphoma models and performed in vitro and in vivo experiments to identify the mechanism of action and the genetic features associated with sensitivity to the compound.

Tradeoff between bleeding and stent thrombosis in different dual antiplatelet therapy regimes: Importance of case fatality rates and effective treatment durations.

Background: The tradeoff between stent thrombosis (ST) and major bleeding (MB) of 12- versus 6-month dual antiplatelet therapy (DAPT) after coronary stent implantation has not been clearly defined.

Methods: Definite/probable ST and MB (TIMI major and Bleeding Academic Research Consortium (BARC) ≥ 3) were compared in 2 subsequent trials with similar inclusion criteria but different DAPT duration, that is, BASKET (6 months; n = 557) and BASKET-PROVE (12 months; n = 2,314), between months 0 to 6 (DAPT in both trials), 7 to 12 (DAPT in BASKET-PROVE only), and 13 to 24 (aspirin in both trials) using propensity score-adjusted, time-stratified Cox proportional hazard models.

Results: Overall, event rates were low with fewer ST but similar MB in prolonged DAPT.

[Important classifications and scores in cardiology].

Classifications and scores play a fundamental role in clinical cardiology. While classification systems may help to quantify symptoms and stages of disease, specific scores enable risk stratification and may facilitate decision-making in various cardiac disorders. The present article reviews some of the most frequently used cardiologic classifications and scores.

PRDM1/BLIMP1 is commonly inactivated in anaplastic large T-cell lymphoma.

Anaplastic large cell lymphoma (ALCL) is a mature T-cell lymphoma that can present as a systemic or primary cutaneous disease. Systemic ALCL represents 2% to 5% of adult lymphoma but up to 30% of all pediatric cases. Two subtypes of systemic ALCL are currently recognized on the basis of the presence of a translocation involving the anaplastic lymphoma kinase ALK gene.

Deregulation of ETS1 and FLI1 contributes to the pathogenesis of diffuse large B-cell lymphoma.

Diffuse large B-cell lymphoma (DLBCL) is the most common form of human lymphoma. DLBCL is a heterogeneous disease characterized by different genetic lesions. We herein report the functional characterization of a recurrent gain mapping on chromosome 11q24.

Cancer risk among tetrafluoroethylene synthesis and polymerization workers.

Tetrafluoroethylene (TFE), a compound used for the production of fluorinated polymers including polytetrafluoroethylene, increases the incidence of liver and kidney cancers and leukemia in rats and mice. This is the first time the cancer risk in humans has been explored comprehensively in a cohort mortality study (1950-2008) that included all polytetrafluoroethylene production sites in Europe and North America at the time it was initiated. A job-exposure matrix (1950-2002) was developed for TFE and ammonium perfluoro-octanoate, a chemical used in the polymerization process.

Studies on metabolically depleted erythrocytes.

Erythrocytes kept outside the blood circulation undergo progressive changes in metabolism, shape and function, which was the topic of this study. For that purpose, blood anticoagulated with either heparin, citrate or EDTA was incubated at temperatures of 5°C, 22°C or 37°C for 0 h, 24 h and 48 h, respectively. A temperature- and time-dependent decrease of glucose and ATP and increase of lactate and LDH were observed.

Intracellular drug release from curcumin-loaded PLGA nanoparticles induces G2/M block in breast cancer cells.

PLGA nanoparticles are among the most studied polymer nanoformulations for several drugs against different kinds of malignant diseases, thanks to their in vivo stability and tumor localization exploiting the well-documented "enhanced permeation and retention" (EPR) effect. In this paper, we have developed uniform curcumin-bearing PLGA nanoparticles by a single-emulsion process, which exhibited a curcumin release following a Fickian-law diffusion over 10 days in vitro. PLGA nanoparticles were about 120 nm in size, as determined by dynamic light scattering, with a surface negative charge of -30 mV.

Botulinum toxin type A injection into the gastrocnemius muscle for spastic equinus in adults with stroke: a randomized controlled trial comparing manual needle placement, electrical stimulation and ultrasonography-guided injection techniques.

Objective: The aim of this study was to compare the clinical outcomes of manual needle placement, electrical stimulation, and ultrasonography-guided techniques for botulinum toxin injection into the gastrocnemius of adults with spastic equinus after stroke.

Design: After randomization into three groups, each patient received the same dose of botulinum toxin type A into the lateral and medial head of the gastrocnemius muscle (OnabotulinumtoxinA, 100U per head) of the affected leg. The manual needle placement group (n = 15) underwent injections using anatomic landmarks and palpation; the electrical stimulation group (n = 15) received injections with electrical stimulation guidance; and the ultrasonography group (n = 17) was injected under sonographic guidance.

Exogenous surfactant replacement: how to deliver it?

Exogenous surfactant is a therapeutic option for newborns, children and adults with acute respiratory distress disorders. Although tracheal instillation is still reputed as the classical method of surfactant delivery, alternative techniques have been investigated. Surfactant administration by using thin intra-tracheal catheters, bronchoscopy, laryngeal mask airway, or nebulisation, although variably effective, appear to be less invasive when compared to tracheal intubation.

Lutein and zeaxanthin supplementation in preterm very low-birth-weight neonates in neonatal intensive care units: a multicenter randomized controlled trial.

Background: Human milk feeding protects against oxidative stress-induced damage in preterm neonates, including severe multifactorial diseases such as retinopathy of prematurity (ROP), necrotizing enterocolitis (NEC), and bronchopulmonary dysplasia (BPD). The carotenoids, which are not found in formula milk, might play a key role in these actions.

Methods: A multicenter, double-blind, randomized controlled trial was conducted in three tertiary Italian neonatal intensive care units.