Funneling Light Through a Subwavelength Aperture with Epsilon-Near-Zero Materials

Integration of the next generation of photonic structures with electronic and optical on-chip components requires the development of effective methods for confining and controlling light in subwavelength volumes. Several techniques enabling light coupling to sub-wavelength objects have recently been proposed, including grating-, and composite-based solutions. However, experi-mental realization of these couplers involves complex fabrication with \sim 10nm resolution in three dimensions. One promising alternative to complex coupling structures involves materials with vanishingly small dielectric permittivity, also known as epsilon-near-zero (ENZ) materials. In contrast to the previously referenced approaches, a single at layer of ENZ-material is expected to provide effcient coupling between free-space radiation and sub-wavelength guiding structures. Here we report the first direct observation of bulk-ENZ-enhanced transmission through a subwavelength slit, accompanied by a theoretical study of this phenomenon. Our study opens the door to multiple practical applications of ENZ materials and ENZ-based photonic systems

Antenatally diagnosed alobar holoprosencephaly: A report of two cases

Holoprosencephaly is a complex developmental abnormality of the brain arising from the failure of cleavage of the prosencephalon. The condition termed “holoprosencephaly” includes cyclopia, cebocephaly, ethmocephaly, and median cleft. We present two cases of antenatally diagnosed alobar holoprosencephaly with multiple associations, which were confirmed after termination of pregnancy. One of them had a proboscis and a single midline eye. The other had multiple facial abnormalities such as hypotelorism, median cleft lip and palate, and preauricular skin tag

Lack of Evidence of Lower 30-Day All-Cause Readmission in Medicare Beneficiaries with Heart Failure and Reduced Ejection Fraction Discharged on Spironolactone

BACKGROUND: Therapy with evidence-based heart failure (HF) medications has been shown to be associated with lower risk of 30-day all-cause readmission in patients with HF and reduced ejection fraction (HFrEF). METHODS: We examined the association of aldosterone antagonist use with 30-day all-cause readmission in this population. Of the 2443 Medicare beneficiaries with HF and left ventricular E

A STAT3 protein complex required for mitochondrial mRNA stability and cancer

Signal transducer and activator of transcription 3 (STAT3) is a potent transcription factor necessary for life whose activity is corrupted in diverse diseases, including cancer. STAT3 biology was presumed to be entirely dependent on its activity as a transcription factor until the discovery of a mitochondrial pool of STAT3, which is necessary for normal tissue function and tumorigenesis. However, the mechanism of this mitochondrial activity remained elusive. This study uses immunoprecipitation and mass spectrometry to identify a complex containing STAT3, leucine-rich pentatricopeptide repeat containing (LRPPRC), and SRA stem-loop-interacting RNA-binding protein (SLIRP) that is required for the stability of mature mitochondrially encoded mRNAs and transport to the mitochondrial ribosome. Moreover, we show that this complex is enriched in patients with lung adenocarcinoma and that its deletion inhibits the growth of lung cancer in vivo, providing therapeutic opportunities through the specific targeting of the mitochondrial activity of STAT3

MYC drives platinum resistant SCLC that is overcome by the dual PI3K-HDAC inhibitor fimepinostat

Abstract Background Small cell lung cancer (SCLC) is an aggressive neuroendocrine cancer with an appalling overall survival of less than 5% (Zimmerman et al. J Thor Oncol 14:768-83, 2019). Patients typically respond to front line platinum-based doublet chemotherapy, but almost universally relapse with drug resistant disease. Elevated MYC expression is common in SCLC and has been associated with platinum resistance. This study evaluates the capacity of MYC to drive platinum resistance and through screening identifies a drug capable of reducing MYC expression and overcoming resistance. Methods Elevated MYC expression following the acquisition of platinum resistance in vitro and in vivo was assessed. Moreover, the capacity of enforced MYC expression to drive platinum resistance was defined in SCLC cell lines and in a genetically engineered mouse model that expresses MYC specifically in lung tumors. High throughput drug screening was used to identify drugs able to kill MYC-expressing, platinum resistant cell lines. The capacity of this drug to treat SCLC was defined in vivo in both transplant models using cell lines and patient derived xenografts and in combination with platinum and etoposide chemotherapy in an autochthonous mouse model of platinum resistant SCLC. Results MYC expression is elevated following the acquisition of platinum resistance and constitutively high MYC expression drives platinum resistance in vitro and in vivo. We show that fimepinostat decreases MYC expression and that it is an effective single agent treatment for SCLC in vitro and in vivo. Indeed, fimepinostat is as effective as platinum-etoposide treatment in vivo. Importantly, when combined with platinum and etoposide, fimepinostat achieves a significant increase in survival. Conclusions MYC is a potent driver of platinum resistance in SCLC that is effectively treated with fimepinostat

Spironolactone Use and Higher Hospital Readmission for Medicare Beneficiaries With Heart Failure, Left Ventricular Ejection Fraction <45%, and Estimated Glomerular Filtration Rate <45 ml/min/1.73 m2

Although randomized controlled trials have demonstrated benefits of aldosterone antagonists for patients with heart failure and reduced ejection fraction (HFrEF), they excluded patients with serum creatinine >2.5 mg/dl, and their use is contraindicated in those with advanced chronic kidney disease (CKD). In the present analysis, we examined the association of spironolactone use with readmission in hospitalized Medicare beneficiaries with HFrEF and advanced CKD. Of the 1,140 patients with HFrEF (EF <45%) and advanced CKD (estimated glomerular filtration rate [eGFR] <45 ml/min/1.73 m(2)), 207 received discharge prescriptions for spironolactone. Using propensity scores (PSs) for the receipt of discharge prescriptions for spironolactone, we estimated PS-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for spironolactone-associated outcomes. Patients (mean age 76 years, 49% women, 25% African-American) had mean EF 28%, mean eGFR 31 ml/min/1.73 m(2), and mean potassium 4.5 mEq/L. Spironolactone use had significant PS-adjusted association with higher risk of 30-day (HR 1.41, 95% CI 1.04 to 1.90) and 1-year (HR 1.36, 95% CI 1.13 to 1.63) all-cause readmissions. The risk of 1-year all-cause readmission was higher among 106 patients with eGFR <15 ml/min/1.73 m(2) (HR 4.75, 95% CI 1.84 to 12.28) than among those with eGFR 15 to 45 ml/min/1.73 m(2) (HR 1.34, 95% CI 1.11 to 1.61, p for interaction 0.003). Spironolactone use had no association with HF readmission and all-cause mortality. In conclusion, among hospitalized patients with HFrEF and advanced CKD, spironolactone use was associated with higher all-cause readmission but had no association with all-cause mortality or HF readmission