The role of canonical and non-canonical Hedgehog signaling in tumor progression in a mouse model of small cell lung cancer.

Hedgehog (Hh) signaling regulates cell fate and self-renewal in development and cancer. Canonical Hh signaling is mediated by Hh ligand binding to the receptor Patched (Ptch), which in turn activates Gli-mediated transcription through Smoothened (Smo), the molecular target of the Hh pathway inhibitors used as cancer therapeutics. Small cell lung cancer (SCLC) is a common, aggressive malignancy with universally poor prognosis.

Intratumoural heterogeneity generated by Notch signalling promotes small-cell lung cancer.

The Notch signalling pathway mediates cell fate decisions and is tumour suppressive or oncogenic depending on the context. During lung development, Notch pathway activation inhibits the differentiation of precursor cells to a neuroendocrine fate. In small-cell lung cancer, an aggressive neuroendocrine lung cancer, loss-of-function mutations in NOTCH genes and the inhibitory effects of ectopic Notch activation indicate that Notch signalling is tumour suppressive.

A tailored mouse model of CLN2 disease: A nonsense mutant for testing personalized therapies.

The Neuronal Ceroid Lipofuscinoses (NCLs), also known as Batten disease, result from mutations in over a dozen genes. Although, adults are susceptible, the NCLs are frequently classified as pediatric neurodegenerative diseases due to their greater pediatric prevalence. Initial clinical presentation usually consists of either seizures or retinopathy but develops to encompass both in conjunction with declining motor and cognitive function.

Swyer-James-MacLeod syndrome with unilateral pulmonary fibrosis: a case report.

Swyer-James-MacLeod syndrome is a rare, complex disease characterized by the radiological finding of unilateral hyperlucent lung due to pulmonary oligaemia and alveolar hyperdistention as a consequence of previous obliterative bronchiolitis (bronchiolitis obliterans). Idiopathic pulmonary fibrosis is a chronic, progressive, fibrosing interstitial pneumonia of unknown cause characterized by bilateral, chronic, progressive and irreversible fibrosis limited to the lungs. We report an interesting case of Swyer-James-MacLeod syndrome affecting one lung and Idiopathic pulmonary fibrosis affecting the contralateral lung.

Quantifying Plasmon-Enhanced Light Absorption in Monolayer WS Films.

Transition metal dichalcogenide semiconductors hold great promise in photonic and optoelectronic applications, such as flexible solar cells and ultrafast photodetectors, because of their direct band gap and few-atom thicknesses. However, it is crucial to understand and improve the absorption characteristics of these monolayer semiconducting materials. In this study, we conducted a systematic numerical and experimental investigation to demonstrate and quantify absorption enhancement in WS monolayer films, in the presence of silver plasmonic nanodisk arrays.

Nonsense pathogenic variants in exon 1 of PHOX2B lead to translational reinitiation in congenital central hypoventilation syndrome.

Pathogenic variants in PHOX2B lead to congenital central hypoventilation syndrome (CCHS), a rare disorder of the nervous system characterized by autonomic dysregulation and hypoventilation typically presenting in the neonatal period, although a milder late-onset (LO) presentation has been reported. More than 90% of cases are caused by polyalanine repeat mutations (PARMs) in the C-terminus of the protein; however non-polyalanine repeat mutations (NPARMs) have been reported. Most NPARMs are located in exon 3 of PHOX2B and result in a more severe clinical presentation including Hirschsprung disease (HSCR) and/or peripheral neuroblastic tumors (PNTs).

A Pharmacy Elective Course on Creative Thinking, Innovation, and TED Talks.

To implement and assess an elective course designed to enhance student creative thinking and presentation skills. A two-credit elective course was developed that incorporated creative-thinking exercises, article discussions pertaining to creativity, TED Talk (TED Conferences, New York, NY) analyses, and presentation design and delivery exercises. Assessment instruments included pre- and post-course Torrance Tests of Creative Thinking (TTCT).

Correlation between Ferumoxytol Uptake in Tumor Lesions by MRI and Response to Nanoliposomal Irinotecan in Patients with Advanced Solid Tumors: A Pilot Study.

To determine whether deposition characteristics of ferumoxytol (FMX) iron nanoparticles in tumors, identified by quantitative MRI, may predict tumor lesion response to nanoliposomal irinotecan (nal-IRI). Eligible patients with previously treated solid tumors had FMX-MRI scans before and following (1, 24, and 72 hours) FMX injection. After MRI acquisition, R2* signal was used to calculate FMX levels in plasma, reference tissue, and tumor lesions by comparison with a phantom-based standard curve.

Practical Insights for the Pharmacist Educator on Student Engagement.

Student engagement continues to be a point of emphasis in pharmacy education, yet there remains little data on tangible means to increase organic student engagement. This review attempts to better define student engagement, draws from educational theorists to emphasize the importance of student engagement, and provides the reader with practice philosophies that can be used across of variety of teaching settings to help develop an engaging learning environment.

Au@MoS Core-Shell Heterostructures with Strong Light-Matter Interactions.

There are emerging opportunities to harness diverse and complex geometric architectures based on nominal two-dimensional atomically layered structures. Herein we report synthesis and properties of a new core-shell heterostructure, termed Au@MoS, where the Au nanoparticle is snugly and contiguously encapsulated by few shells of MoS atomic layers. The heterostructures were synthesized by direct growth of multilayer fullerene-like MoS shell on Au nanoparticle cores.

Synergistic photomagnetic effects in coordination polymer heterostructure particles of Hofmann-like Fe(4-phenylpyridine)[Ni(CN)]·0.5HO and KNi[Cr(CN)]·nHO.

New nanometer scale heterostructure particles of the two-dimensional Hofmann-like Fe(ii) spin-crossover network, Fe(phpy)[Ni(CN)]·0.5HO {phpy = 4-phenylpyridine}, and the Prussian blue analogue KNi[Cr(CN)]·nHO (NiCr-PBA) have been developed, exhibiting synergistic photomagnetic effects, whereby the LIESST (light-induced electron spin-state trapping) effect in the Hofmann-like material induces a magnetization change in the NiCr-PBA. A variety of microscopic and spectroscopic techniques demonstrate the heterogeneous growth of the NiCr-PBA on the Hofmann seed particles and show the Hofmann compound retains its thermal and photoinduced spin transition properties in the heterostructure.

Effects of Medial Displacement Calcaneal Osteotomy and Calcaneal Z Osteotomy on Subtalar Joint Pressures: A Cadaveric Flatfoot Model.

Medial displacement calcaneal osteotomies have been shown to be successful in the surgical management of adult acquired flatfoot, in particular, stage 2 deformity. Classically, the medial displacement calcaneal osteotomy technique has been performed. However, a calcaneal Z osteotomy has been more recently described and applied in the surgical management of flatfoot deformity.

Mitochondrial DNA plasticity is an essential inducer of tumorigenesis.

Although mitochondrial DNA has been implicated in diseases such as cancer, its role remains to be defined. Using three models of tumorigenesis, namely glioblastoma multiforme, multiple myeloma and osteosarcoma, we show that mitochondrial DNA plays defining roles at early and late tumour progression. Specifically, tumour cells partially or completely depleted of mitochondrial DNA either restored their mitochondrial DNA content or actively recruited mitochondrial DNA, which affected the rate of tumorigenesis.

Cross-frequency coherence and pulse propagation in a turbulent atmosphere.

Cross-frequency coherence of acoustic signals in a turbulent atmosphere is an important consideration for source localization with acoustic sensor arrays and for remote sensing of the atmosphere with sodars and tomography techniques. This paper takes as a starting point recently derived, closed-form equations for the spatial-temporal correlation function of a broadband acoustic signal propagating in a turbulent atmosphere with coupled spatial-temporal fluctuations in temperature and wind velocity. This theory is employed to calculate, based on the Rytov approximation, the two-point, two-time, two-frequency mutual coherence function of plane and spherical waves in the weak scattering regime.

The Emerging Issue of Digital Empathy.

Empathy can have strong positive effects on patient outcomes, increase patient satisfaction, and reduce malpractice litigation. With modern advances in technology, however, the appropriate expression of empathy in today's age is being threatened, largely as a result of psychological processes that form online disinhibition. The digitization of health care and the corresponding decrease in the expression of empathy may be cause for concern.

A first look at the Accreditation Council for Graduate Medical Education anesthesiology milestones: implementation of self-evaluation in a large residency program.

Study Objective: The objective was to determine if there is a correlation between resident postgraduate year (PGY) of training and self-evaluation of performance using the Accreditation Council for Graduate Medical Education milestones.

Design: Survey.

Setting: Residency program at a large academic center.

Therapeutic Impact of Cytoreductive Surgery and Irradiation of Posterior Fossa Ependymoma in the Molecular Era: A Retrospective Multicohort Analysis.

Purpose: Posterior fossa ependymoma comprises two distinct molecular variants termed EPN_PFA and EPN_PFB that have a distinct biology and natural history. The therapeutic value of cytoreductive surgery and radiation therapy for posterior fossa ependymoma after accounting for molecular subgroup is not known.

Methods: Four independent nonoverlapping retrospective cohorts of posterior fossa ependymomas (n = 820) were profiled using genome-wide methylation arrays.

Accelerating the pace of discovery in orthopaedic research: A vision toward team science.

The landscape of basic science in the United States and around the world is changing, and the field of orthopaedic research is positioned to lead by embracing a culture of collaborative, team science that reflects our field's interdisciplinary nature. In this article we hope to address some of the cultural challenges and programmatic barriers that impede a team science approach in the US and suggest opportunities for change. © 2016 Orthopaedic Research Society.

Activating Transcription Factor 3 Expression as a Marker of Response to the Histone Deacetylase Inhibitor Pracinostat.

Improved treatment strategies are required for bladder cancer due to frequent recurrence of low-grade tumors and poor survival rate from high-grade tumors with current therapies. Histone deacetylase inhibitors (HDACi), approved as single agents for specific lymphomas, have shown promising preclinical results in solid tumors but could benefit from identification of biomarkers for response. Loss of activating transcription factor 3 (ATF3) expression is a feature of bladder tumor progression and correlates with poor survival.

Note-taking and Handouts in The Digital Age.

Most educators consider note-taking a critical component of formal classroom learning. Advancements in technology such as tablet computers, mobile applications, and recorded lectures are altering classroom dynamics and affecting the way students compose and review class notes. These tools may improve a student's ability to take notes, but they also may hinder learning.

Cre-dependent DNA recombination activates a STING-dependent innate immune response.

Gene-recombinase technologies, such as Cre/loxP-mediated DNA recombination, are important tools in the study of gene function, but have potential side effects due to damaging activity on DNA. Here we show that DNA recombination by Cre instigates a robust antiviral response in mammalian cells, independent of legitimate loxP recombination. This is due to the recruitment of the cytosolic DNA sensor STING, concurrent with Cre-dependent DNA damage and the accumulation of cytoplasmic DNA.

Therapeutic effect of flax-based diets on fatty liver in aged laying hens.

This study examined the ability of flax-based ingredients to attenuate nonalcoholic fatty liver disease ( NAFLD: ) in aged laying hens-a novel and more physiologically relevant model of human disease. Our results showed only hens supplemented with whole flaxseed ( WFX: ) reduced steatosis and hepatocellular ballooning. Serum AST was also reduced in hens provided WFX and defatted flaxseed meal ( DFM: ).