A multicenter, open-label, randomized, phase II study of cediranib with or without lenalidomide in iodine 131-refractory differentiated thyroid cancer.

BACKGROUND: Multitargeted tyrosine kinase inhibitors (TKIs) of the vascular endothelial growth factor receptor (VEGFR) pathway have activity in differentiated thyroid cancer (DTC). Lenalidomide demonstrated preliminary efficacy in DTC, but its safety and efficacy in combination with VEGFR-targeted TKIs is unknown. We sought to determine the safety and efficacy of cediranib, a VEGFR-targeted TKI, with or without lenalidomide, in the treatment of iodine 131-refractory DTC. PATIENTS AND METHODS: In this multicenter, open-label, randomized, phase II clinical trial, 110 patients were enrolled and randomized to cediranib alone or cediranib with lenalidomide. The primary endpoint was progression-free survival (PFS). Secondary endpoints included response rate, duration of response, toxicity, and overall survival (OS). Patients (≥18 years of age) with DTC who were refractory to further surgical or radioactive iodine (RAI) therapy as reviewed at a multispecialty tumor board conference, and evidence of disease progression within the previous 12 months and no more than one prior line of systemic therapy were eligible. RESULTS: Of the 110 patients, 108 started therapy and were assessable for efficacy. The median PFS was 14.8 months [95% confidence interval (CI) 8.5-23.8 months] in the cediranib arm and 11.3 months (95% CI 8.7-18.9 months) in the cediranib with lenalidomide arm (P = 0.36). The 2-year OS was 64.8% (95% CI 43.3% to 86.4%) and 75.3% (95% CI 59.4% to 91.0%), respectively (P = 0.80). The serious adverse event rate was 41% in the cediranib arm and 46% in the cediranib with lenalidomide arm. CONCLUSIONS: Single-agent therapy with cediranib showed promising efficacy in RAI-refractory DTC similar to other VEGFR-targeted TKIs, while the addition of lenalidomide did not result in clinically meaningful improvements in outcomes.

Sjögren's syndrome associated with protein losing gastroenteropathy manifested by intestinal lymphangiectasia successfully treated with prednisolone and hydroxychloroquine.

Protein-losing gastroenteropathy (PLGE), a rare manifestation of primary Sjögren's syndrome (SS), is characterized by profound edema and severe hypoalbuminemia secondary to excessive serum protein loss from the gastrointestinal tract and is clinically indistinguishable from nephrotic syndrome. We report a case of a 30-year-old Taiwanese woman with PLGE-associated SS. In addition to a positive Schirmer's test, she had eye-dryness, thirst, and high levels of anti-SSA antibodies, fulfilling SS criteria. PLGE diagnosis was highly appropriate given the clinical profile of hypoalbuminemia, hypercholesterolemia, pleural effusion, and ascites, with absent cardiac, hepatic, or renal disease. We were unable to perform technetium-99 m-labeled human serum albumin scintigraphy ((99m)Tc-HAS). However, the patient's edema and albumin level improved dramatically in response to a 3-month regime of oral prednisolone followed by oral hydroxychloroquine.

Deep sequencing of small RNA libraries reveals dynamic expression patterns of microRNAs in multiple developmental stages of Bactrocera dorsalis.

In eukaryotes, microRNAs (miRNAs) are small, conserved, noncoding RNAs that have emerged as critical regulators of gene expression. The oriental fruit fly Bactrocera dorsalis is one of the most economically important fruit fly pests in East Asia and the Pacific. Although transcriptome analyses have greatly enriched our knowledge of its structural genes, little is known about post-transcriptional regulation by miRNAs in this dipteran species. In this study, small RNA libraries corresponding to four B. dorsalis developmental stages (eggs, larvae, pupae and adults) were constructed and sequenced. Approximately 30.7 million reads of 18-30 nucleotides were obtained, with 123 known miRNAs and 60 novel miRNAs identified amongst these libraries. More than half of the miRNAs were stage-specific during the four developmental stages. A set of miRNAs was found to be up- or down-regulated during development by comparison of their reads at different developmental stages. Moreover, a small part of miRNAs owned both miR-#-3p and miR-#-5p types, with enormously variable miR-#-3p/miR-#-5p ratios in the same library and amongst different developmental stages for each miRNA. Taking these findings together, the current study has uncovered a number of miRNAs and provided insights into their possible involvement in developmental regulation by expression profiling of miRNAs. Further analyses of the expression and function of these miRNAs could increase our understanding of regulatory networks in this insect and lead to novel approaches for its control.

An analysis of the small RNA transcriptome of four developmental stages of the citrus red mite (Panonychus citri).

The citrus red mite (Panonychus citri) can feed on more than 112 plant species around the world. Endogenous small RNAs (sRNAs) have proved to be important components of gene regulation in many eukaryotes. Recently, many sRNAs have been shown to be involved in various biological processes, such as development in many animals, including insects; however, to date, no sRNAs have been reported in the citrus red mite. Using Illumina sequencing, several categories of sRNAs were identified, including 594 known microRNAs (miRNAs) grouped into 206 families and 31 novel miRNAs in the four developmental stages of citrus red mite. In addition, according to bioinformatics analysis and S-Poly(T) miRNA assays, the expression level of many miRNAs varied among the developmental stages. Furthermore, the prediction of miRNAs target genes and their functional annotation indicated that miRNAs are involved in the regulation of multiple pathways in the citrus red mite. As the first report of the sRNA world in citrus red mite, the present study furthers our understanding of the roles played by sRNAs in the development of citrus red mite and the data may help to develop methods of controlling the pests in the field.

Interstitial-mediated diffusion in germanium under proton irradiation.

We report experiments on the impact of 2.5 MeV proton irradiation on self-diffusion and dopant diffusion in germanium (Ge). Self-diffusion under irradiation reveals an unusual depth independent broadening of the Ge isotope multilayer structure. This behavior and the observed enhanced diffusion of B and retarded diffusion of P demonstrates that an interstitial-mediated diffusion process dominates in Ge under irradiation. This fundamental finding opens up unique ways to suppress vacancy-mediated diffusion in Ge and to solve the donor deactivation problem that hinders the fabrication of Ge-based nanoelectronic devices.

The diagnostic utility of preoperative breast magnetic resonance imaging (MRI) and/or intraoperative sub-nipple biopsy in nipple-sparing mastectomy.

BACKGROUND: The necessity of routine sub-nipple biopsy was uncertain, and the role of preoperative magnetic resonance imaging (MRI) in detecting nipple invasion in patients who have been selected for nipple sparing mastectomy (NSM) has not been adequately evaluated. METHODS: We retrospectively collected and analyzed the medical and surgical records of 434 patients with primary operable breast cancer who met the criteria for NSM and underwent breast surgery during the period January 2011 to December 2015. Patients were stratified into three risk groups (low, intermediate, and high) according to tumor size and tumor-to-nipple distance. RESULTS: Among the 434 patients in this study, 29 (6.7%) had occult invasion of the nipple-areola complex (NAC). Sub-nipple biopsy had a sensitivity of 84.6%, a specificity of 100%, a false negative rate of 1.2%, a false positive rate of 0%, and an overall accuracy rate of 98.8% in confirming NAC invasion. The NAC invasion rate was 0% in the low-risk group, 5.1% in the intermediate-risk group, and 19.7% in the high-risk group (P < 0.01). The overall NPV of preoperative MRI for predicting NAC invasion was 94.8%. Cost analysis revealed that the cost of NSM with sub-nipple biopsy was significantly higher than that of NSM alone, with a mean difference in cost of USD 238.5 (P < 0.01). CONCLUSION: The high negative predictive value of MRI for NAC invasion is useful for selection of patients receiving NSM. Sub-nipple biopsy is a reliable procedure to detect occult NAC invasion, however, routine use is not cost-effect for low risk patients.

Dynamics of inherent structure in supercooled liquids near kinetic glass transition.

We present a description of the dynamics of a supercooled binary Lennard-Jones liquid in term of the potential landscape of the system. The slowing down of the dynamics in supercooled liquids near the kinetic glass transition is related to the existence of basins in the potential landscape. The inherent structures that are the local potential minima in the configuration space obtained by a quench process are employed to represent the configurations of the basins. We present time correlation functions of the inherent structure, both the self and the coherent part, as a function of wave vector. We also calculated the mean-square displacement, and the non-Gaussian parameter of the van Hove self-correlation function. Compared with the dynamics of original configurations, the short-time relaxation has almost been eliminated by the quench process. However, the long-time alpha relaxations remain essentially the same. We conclude that the long-time alpha relaxation is the result of cross-basin transition in the potential landscape in the configuration space.

[QTLs and epistasis underlying rice (Oryza sativa L.) panicle length in different genetic background and environments].

A double haploid (DH) population and a recombinant inbred (RI) population derived from a cross between a japonica male parent Azucena and indica female parents, IR64 and IR1552 respectively, were used in both field and pot experiments for detecting QTLs and epistasis for rice panicle length in different genetic background and different environments. Panicle length (PL) was measured at maturity. QTLs for PL were detected using single marker analysis and interval mapping. Epistasis effects on the trait were also analyzed. Nine QTLs were detected in DH population, including 5 QTLs detected from field experiment and 4 from pot experiment, among them 3 QTLs mapped on chromosomes 1 and 4 were identified in both field and pot experiments. No significant epistasis effect was detected for PL. Four QTLs were detected in RI population, among them 2 from field condition and 2 from pot experiment. 6 pairs of epistasis loci were detected in RI population. One QTL mapped on chromosome 4 and two pairs of epistatic loci were detected in both field and pot experiments. One QTL on chromosome four was identified in both populations, and one marker locus RG323 on chromosome one was involved in additive effect in DH population, but epistasis effects in RI population.

Efficient delayed fluorescence via triplet-triplet annihilation for deep-blue electroluminescence.

Four 2-(styryl)triphenylene derivatives (TSs) were synthesized for deep-blue dopant materials. By using a pyrene-containing compound, DMPPP, as the host, the TS-doped devices exhibited significant delayed fluorescence via triplet-triplet annihilation, providing the highest quantum efficiency of 10.2% and a current efficiency of 12.3 cd A(-1).

Theory of nanocluster size distributions from ion beam synthesis.

Ion beam synthesis of nanoclusters is studied via both kinetic Monte Carlo simulations and the self-consistent mean-field solution to a set of coupled rate equations. Both approaches predict the existence of a steady-state shape for the cluster-size distribution that depends only on a characteristic length determined by the effective diffusion coefficient, the ion solubility, and the volumetric ion flux. The average cluster size in the steady-state regime is determined by the implanted species or matrix interface energy.