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Nowadays, in a communicating society, fashion is an integral part of a human life, and it is more comfortable and confident when people dress well. Outfit compatibility is not only a combination of different items but also regarding various aspects, such as style, user preferences, and specific occasions. Most of the existing works lead to address the outfit compatibility concerning only style or user preferences, and have no regard for occasions. In this paper, we propose an efficient method for both outfit compatibility and the fill-in-the-blank tasks according to specific occasions. To this end, we utilized an auxiliary classification branch to learn the significantly important features regarding specific occasions. Besides, a sequence to sequence approach is also applied to learn the relationship of different items along with a visual semantic space, which is able to learn the connection between visual features and their semantic presentation. To demonstrate the effectiveness of the proposed method, we conduct experiments on our newly collected Shoplook-Occasion dataset. The experimental results indicate that our proposed method improved the AUC metric from 0.02 to 0.15% and from 0.5 to 4% on accuracy, compared with other approaches for outfit compatibility problem conditioning on specific occasions.

Supplementary Methods and Data

Myelofibrosis (myelofibrosis) is a deadly blood neoplasia with the worst prognosis among myeloproliferative neoplasms (MPN). The JAK2 inhibitors ruxolitinib and fedratinib have been approved for treatment of myelofibrosis, but they do not offer significant improvement of bone marrow fibrosis. CDK6 expression is significantly elevated in MPN/myelofibrosis hematopoietic progenitor cells. In this study, we investigated the efficacy of CDK4/6 inhibitor palbociclib alone or in combination with ruxolitinib in Jak2V617F and MPLW515L murine models of myelofibrosis. Treatment with palbociclib alone significantly reduced leukocytosis and splenomegaly and inhibited bone marrow fibrosis in Jak2V617F and MPLW515L mouse models of myelofibrosis. Combined treatment of palbociclib and ruxolitinib resulted in normalization of peripheral blood leukocyte counts, marked reduction of spleen size, and abrogation of bone marrow fibrosis in murine models of myelofibrosis. Palbociclib treatment also preferentially inhibited Jak2V617F mutant hematopoietic progenitors in mice. Mechanistically, treatment with palbociclib or depletion of CDK6 inhibited Aurora kinase, NF-κB, and TGFβ signaling pathways in Jak2V617F mutant hematopoietic cells and attenuated expression of fibrotic markers in the bone marrow. Overall, these data suggest that palbociclib in combination with ruxolitinib may have therapeutic potential for treatment of myelofibrosis and support the clinical investigation of this drug combination in patients with myelofibrosis.Significance:These findings demonstrate that CDK6 inhibitor palbociclib in combination with ruxolitinib ameliorates myelofibrosis, suggesting this drug combination could be an effective therapeutic strategy against this devastating blood disorder.

Recent advances in drug development have seen numerous successful clinical translations using synthetic antisense oligonucleotides (ASOs). However, major obstacles, such as challenging large-scale production, toxicity, localization of oligonucleotides in specific cellular compartments or tissues, and the high cost of treatment, need to be addressed. Thiomorpholino oligonucleotides (TMOs) are a recently developed novel nucleic acid analog that may potentially address these issues. TMOs are composed of a morpholino nucleoside joined by thiophosphoramidate internucleotide linkages. Unlike phosphorodiamidate morpholino oligomers (PMOs) that are currently used in various splice-switching ASO drugs, TMOs can be synthesized using solid-phase oligonucleotide synthesis methodologies. In this study, we synthesized various TMOs and evaluated their efficacy to induce exon skipping in a Duchenne muscular dystrophy (DMD) in vitro model using H2K mdx mouse myotubes. Our experiments demonstrated that TMOs can efficiently internalize and induce excellent exon 23 skipping potency compared with a conventional PMO control and other widely used nucleotide analogs, such as 2′-O-methyl and 2′-O-methoxyethyl ASOs. Notably, TMOs performed well at low concentrations (5–20 nM). Therefore, the dosages can be minimized, which may improve the drug safety profile. Based on the present study, we propose that TMOs represent a new, promising class of nucleic acid analogs for future oligonucleotide therapeutic development.

Myelofibrosis (myelofibrosis) is a deadly blood neoplasia with the worst prognosis among myeloproliferative neoplasms (MPN). The JAK2 inhibitors ruxolitinib and fedratinib have been approved for treatment of myelofibrosis, but they do not offer significant improvement of bone marrow fibrosis. CDK6 expression is significantly elevated in MPN/myelofibrosis hematopoietic progenitor cells. In this study, we investigated the efficacy of CDK4/6 inhibitor palbociclib alone or in combination with ruxolitinib in Jak2V617F and MPLW515L murine models of myelofibrosis. Treatment with palbociclib alone significantly reduced leukocytosis and splenomegaly and inhibited bone marrow fibrosis in Jak2V617F and MPLW515L mouse models of myelofibrosis. Combined treatment of palbociclib and ruxolitinib resulted in normalization of peripheral blood leukocyte counts, marked reduction of spleen size, and abrogation of bone marrow fibrosis in murine models of myelofibrosis. Palbociclib treatment also preferentially inhibited Jak2V617F mutant hematopoietic progenitors in mice. Mechanistically, treatment with palbociclib or depletion of CDK6 inhibited Aurora kinase, NF-κB, and TGFβ signaling pathways in Jak2V617F mutant hematopoietic cells and attenuated expression of fibrotic markers in the bone marrow. Overall, these data suggest that palbociclib in combination with ruxolitinib may have therapeutic potential for treatment of myelofibrosis and support the clinical investigation of this drug combination in patients with myelofibrosis. Significance: These findings demonstrate that CDK6 inhibitor palbociclib in combination with ruxolitinib ameliorates myelofibrosis, suggesting this drug combination could be an effective therapeutic strategy against this devastating blood disorder.

U2AF1 is involved in the recognition of the 3' splice site during pre-mRNA splicing. Mutations in U2AF1 are frequently observed in myelodysplastic syndromes. However, the role of wild-type U2AF1 in normal hematopoiesis has remained elusive. Using a novel conditional U2af1 knockout allele, we have found that deletion of U2af1 results in profound defects in hematopoiesis characterized by pancytopenia, ablation of hematopoietic stem/progenitor cells (HSPC) leading to bone marrow failure and early lethality in mice. U2af1 deletion impairs HSPC function and repopulation capacity. U2af1 deletion also causes increased DNA damage and reduced survival in hematopoietic progenitors. RNA sequencing analysis reveals significant alterations in the expression of genes related to HSC maintenance, cell proliferation, and DNA damage response-related pathways in U2af1-deficient HSPC. U2af1 deficiency also induces splicing alterations in genes important for HSPC function. This includes altered splicing and perturbed expression of Nfya and Pbx1 transcription factors in U2af1-deficient HSPC. Collectively, these results suggest an important role for U2af1 in the maintenance and function of HSPC in normal hematopoiesis. A better understanding of the normal function of U2AF1 in hematopoiesis is important for development of appropriate therapeutic approaches for U2AF1 mutant induced hematologic malignancies.

Synthetic antisense oligonucleotides (ASOs) have emerged as one of the most promising therapeutic approaches. So far, nine ASO drugs have received approval for clinical use, and four of them are based on splice-switching principles demonstrating the impact of ASO-mediated splice modulation. Notably, three among them (Exondys 51, Vyondys 53 and Viltepso) are based on phosphorodiamidate morpholino (PMO) chemistry whereas Spinraza is based on 2′-O-methoxyethyl phosphorothioate (2′-MOE PS) chemistry. Although systemic delivery of PMOs has displayed a good safety profile even at high doses, the 2′-O-methyl phosphorothioate modified (2′-OMe PS) ASO drug candidate (drisapersen) failed due to safety issues. The potency of 2′-modified RNA for splice-switching needs to be further improved by novel design strategies for broad applicability. Towards this goal, in this study, we evaluated the potential of incorporating DNA segments at appropriate sites in 2′-OMe PS and 2′-MOE PS ASOs to induce exon skipping. For this purpose, a four-nucleotide DNA segment was systematically incorporated into a 20-mer 2′-OMe PS and 2′-MOE PS ASO designed to skip exon 23 in mdx mouse myotubes in vitro. Our results demonstrated that 2′-modified RNA PS ASOs containing four or less PS DNA nucleotides at the 3′-end yielded improved exon 23 skipping efficacy in line with fully modified ASO controls. Based on these results, we firmly believe that the present study opens new avenues towards designing splice modulating ASOs with limited chemical modifications for enhanced safety and therapeutic efficacy.

One of the difficulties of the subintimal arterial flossing with antegrade-retrograde intervention technique (SAFARI) technique is to properly achieve a rendezvous between both antegrade and retrograde accesses. We propose a new technique to overcome this difficulty. It consists of directly percutaneously puncturing 2 loop snares, placed via each access, which are then both used to snare an externally introduced guidewire introduced through the needle. The snares are then moved en bloc, bringing both snares and the wire into the same channel.

We have found that antisense oligonucleotides and siRNA molecules modified with repeat structures of disulfide units can be directly introduced into the cytoplasm and exhibit a suppressive effect on gene expression. In this study, we analyzed the mechanism of cellular uptake of these membrane-permeable oligonucleotides (MPONs). Time-course analysis by confocal microscopy showed that the uptake of MPONs from the plasma membrane to the cytoplasm reached 50 % of the total uptake in about 5 min. In addition, analysis of the plasma membrane proteins to which MPONs bind, identified several proteins, including voltage-dependent anion channel. Next, we analyzed the behavior of MPONs in the cell and found them to be abundant in the nucleus as early as 24 h after addition with the amount increasing further after 48 and 72 h. The amount of MPONs was 2.5-fold higher than that of unmodified oligonucleotides in the nucleus after 72 h. We also designed antisense oligonucleotides and evaluated the effect of MPONs on mRNA exon skipping using DMD model cells; MPONs caused exon skipping with 69 % efficiency after 72 h, which was three times higher than the rate of the control. In summary, the high capacity for intracytoplasmic and nuclear translocation of MPONs is expected to be useful for therapeutic strategies targeting exon skipping.

Chronic inflammation is frequently associated with myeloproliferative neoplasms (MPN), but the role of inflammation in the pathogenesis of MPN remains unclear. Expression of the proinflammatory cytokine interleukin-1 (IL-1) is elevated in patients with MPN as well as in Jak2V617F knock-in mice. Here, we show that genetic deletion of IL-1 receptor 1 (IL-1R1) normalizes peripheral blood counts, reduces splenomegaly and ameliorates bone marrow fibrosis in homozygous Jak2V617F mouse model of myelofibrosis. Deletion of IL-1R1 also significantly reduces Jak2V617F mutant hematopoietic stem/progenitor cells. Exogenous administration of IL-1β enhances myeloid cell expansion and accelerates the development of bone marrow fibrosis in heterozygous Jak2V617F mice. Furthermore, treatment with anti-IL-1R1 antibodies significantly reduces leukocytosis and splenomegaly, and ameliorates bone marrow fibrosis in homozygous Jak2V617F mice. Collectively, these results suggest that IL-1 signaling plays a pathogenic role in MPN disease progression, and targeting of IL-1R1 could be a useful strategy for the treatment of myelofibrosis.

Image captioning tries to make computer learn to understand the visual content of a given image and produce one or more description sentences. Recently, with the help from rapid development of deep learning, image captioning has become an active research. The encoder-decoder architecture is commonly considered as the baseline method to address image captioning. This model focuses on recognizing objects and the relationship among these objects. However, with fashion images, the generated sentence should not only describe items inside the input image, but also mention item attributes such as texture, fabric, shape, style, etc. This requirement of fashion image captioning is not able to be solved by the image-captioning method based on the traditional encoder-decoder architecture. Our study addresses this issue by proposing an image captioning model based on the attention mechanism for fashion image which is able to cover both items and the relationship among the detailed attributes of items. We introduce an efficient framework for fashion image captioning that incorporates spatial attention inside the traditional encoder-decoder architecture. Our model generates fashion image captions using the spatial attention mechanism, which dynamically modulates the sentence generation context in multi-layer feature maps. Experiments were conducted on Fashion-Gen, one of state-of-the-art fashion image dataset, and achieved CIDEr/ROUGE-L/BLEU-4 scores of 0.913, 0.502, and 0.221, respectively. Based on experiments, it is consistently presented that our proposed model has significantly improved the performance of fashion-image captioning task, and it even surpasses the baseline methods on the same fashion benchmark dataset.

Performance guarantees and tests of thermal power plants are usually carried out at 100% rate output capacity. However, fossil-fired power plants have decreased full load hours, affecting energy efficiency, and are subjected to frequent load changes caused by variable renewable electricity and potential grid stability. Therefore, this study is conducted to calculate and draw the characteristic curves for all stable loads of coal-fired power units including the 60%, 75%, and 100% rate output. The study focuses on the corrected plant net heat rates—gross unit outputs, net standard coal consumption rates—throttle steam pressures, and corrected plant net efficiencies—carbonic emission rates. In addition, the experimental investigation for energy efficiency and carbonic emission of the latest larger-scale (+600 MW) coal-fired power generation units in Vietnam are also implemented using a performance guarantee calculation software called “PG_Cal” version 0.0, which is based on a mass and energy balance method by MATLAB programing language. From the results of this study, it is suggested that the performance guarantees and tests of new coal-fired units should be carried out at different stable loads, including minimum load. Vietnam should apply the ultra-supercritical technology for new units in order to increase their efficiency and decrease carbon dioxide emissions.

In normal condition of thermal power plant, the boiler feed-water pump (BFP) speed modulates to control economizer feed-water (FW) flow, and/or the regulation valve is used for start-up and low load. However, super-critical motor-BFP at its minimum speed can not sufficiently modulate to control economizer FW flow during low pressure boiler start-up. Moreover, the requirement of high drop pressure can not be achieved with one control valve given the wide flow control range required. Therefore, the study conducts the experiment and evaluation for a novel design with additional letdown control valves downstream pump in series with regulation valve to control feed-water during unit start-up and low load for the configuration of super-critical Motor-BFP. The results show that the ramp rates of temperature and pressure per minutes are equivalent and within permission of ASME codes in comparison with the configuration of sub-critical Motor-BFP with one control valve during start-up time tests. From the results of the study, it is advisable that Vietnam can apply this viable design for the new thermal power units in order to proof against the increase of periodic start-ups or partial shutdowns caused by the problems related to variable renewable electricity and potential grid stability in the near future.

How stem cells give rise to epidermis is unclear despite the crucial role the epidermis plays in barrier and appendage formation. Here we use single cell-RNA sequencing to interrogate basal stem cell heterogeneity of human interfollicular epidermis and find four spatially distinct stem cell populations at the top and bottom of rete ridges and transitional positions between the basal and suprabasal epidermal layers. Cell-cell communication modeling suggests that basal cell populations serve as crucial signaling hubs to maintain epidermal communication. Combining pseudotime, RNA velocity, and cellular entropy analyses point to a hierarchical differentiation lineage supporting multi-stem cell interfollicular epidermal homeostasis models and suggest that transitional basal stem cells are stable states essential for proper stratification. Finally, alterations in differentially expressed transitional basal stem cell genes result in severe thinning of human skin equivalents, validating their essential role in epidermal homeostasis and reinforcing the critical nature of basal stem cell heterogeneity., The mechanisms regulating stem cells to give rise to human interfollicular epidermis are unclear. Here, the authors use single cell RNA sequencing to identify heterogeneity within the human neonatal interfollicular epidermis and distinct spatial positioning of at least four basal stem cell populations.

Copyright © 2019 American Chemical Society. Domestic wastewater depth processing and reclamation are essential in the alleviation of global water shortage. In this study, an innovative filter media (i.e., Fe3O4@Carbon filter media [FCM]) was synthesized and subsequently used in a biological aerated filter (BAF) for simultaneous phosphate recovery and nitrogen removal (SPN) from domestic wastewater. The performance of FCM was compared with the commercially available ceramsite (CAC). The results showed that the performance of FCMBAF was better than that of CACBAF; as far as SPN is concerned, the magnetic field of FCMBAF could accelerate the growth rate of biofilm. Moreover, the nitrospira and nirK gene copy numbers of FCMBAF were considerably higher than those of CACBAF. Interestingly, the interconnectivity and uniformity of pores were also suitable for the microdistribution of biofilm, where different aerobic and anaerobic zones of the FCM were formed. This facilitates the microinteraction between the key microorganisms and the filter media that successfully enhanced the nitrogen removal. The phosphate recovery was attained via hydroxyapatite (Ca10(PO4)6(OH)2) formation, which resulted from the reaction between phosphate (PO43-) and FCM. The average effluent concentrations of total organic carbon (TOC), total nitrogen (TN), ammonia nitrogen (NH4+-N), and PO43- were 8.12, 6.18, 0.997, and 0.073 mg/L of FCMBAF, respectively, which were lower than those from the national standard (CODcr ≤ 50 mg L-1, NH4+-N ≤ 5.0 mg L-1, TN ≤ 15 mg L-1, TP ≤ 0.5 mg L-1, GB 18918-2002, first standard). Thus, FCM demonstrated a promising potential for SPN and wastewater recycling of BAF in domestic wastewater treatment.

Myeloproliferative neoplasms (MPN) are a group of clonal hematopoietic stem cell derived myeloid malignancies characterized by aberrant production of myeloid, erythroid or megakaryocytic lineage cells. JAK2V617F is the most common somatic driver mutation associated with MPN. Interestingly, JAK2V617F mutation can also be detected in healthy individuals with clonal hematopoiesis of indeterminate potential (CHIP) who do not exhibit overt changes in blood counts. This suggests that other factors might be involved in association with JAK2 mutation in clonal expansion and initiation/progression of MPN. Chronic inflammation is frequently associated with MPN. Interleukin 1 (IL-1) is a major regulator of inflammation. IL-1 consists of two related cytokines IL-1α and IL-1β. Both IL-1α and IL-1β bind to the IL-1 receptor 1 (IL-1R1) to initiate downstream signaling. Although elevated expression of IL-1α and IL-1β has been observed in MPN, their role in the pathogenesis of MPN has remained elusive. In this study, we investigated the role of IL-1 signaling in JAK2V617F-induced MPN using a Jak2V617F knock-in mouse model. We observed elevated levels of IL-1α and IL-1β in mice expressing heterozygous (Jak2 VF/+) and homozygous Jak2V617F (Jak2 VF/VF) compared with WT control animals. Notably, IL-1α and IL-1β expression was significantly higher in Jak2 VF/VF mice exhibiting extensive bone marrow (BM) fibrosis compared with Jak2 VF/+ mice exhibiting polycythemia vera (PV), consistent with elevated levels of IL-1 in patients with myelofibrosis (MF). Since both IL-1α and IL-1β levels were elevated in Jak2 VF/VF mice exhibiting MF, we utilized conditional IL-1R1 knockout (IL-1R1cKO) and Jak2 VF/VF mice to assess the role of IL-1 signaling in the initiation/progression of MF. As expected, Jak2 VF/VF mice exhibited a significant increase in WBC, neutrophil and platelet counts compared to WT control mice. Deletion of IL-1R1in Jak2 VF/VF mice (IL-1R1cKO; Jak2 VF/VF) significantly reduced the WBC, neutrophil and platelet counts to almost control levels. Flow cytometric analysis also showed a significant reduction of myeloid (Gr-1 +) and megakaryocytic (CD41 +) precursors in the BM and spleens of IL-1R1cKO; Jak2 VF/VF mice compared to Jak2 VF/VF mice. Moreover, deletion of IL-1R1 significantly reduced hematopoietic stem and progenitor cells (HSPC) in the BM of IL-1R1cKO; Jak2 VF/VF mice compared to Jak2 VF/VF mice. Spleen weight was significantly reduced in IL-1R1cKO; Jak2 VF/VF mice compared with Jak2 VF/VF mice and they were comparable to control WT mice. More importantly, deletion of IL-1R1 markedly reduced BM fibrosis in Jak2 VF/VF mice. These data suggest an important role of IL-1 signaling in the progression of BM fibrosis in Jak2V617F-induced MPN. To test whether IL-1 signaling contributes to clonal expansion of JAK2 mutant HSPC, we performed competitive transplantation assays by mixing Mx1Cre; Jak2 VF/+ and Mx1Cre; IL-1R1 F/F; Jak2 VF/+ mice BM cells with CD45.1 + WT mice BM cells at a ratio of 1:1 and transplanted into lethally irradiated CD45.1 + recipient animals. At 4 weeks after BMT, the recipient animals were injected with pI-pC to induce Jak2V617F expression and IL-1R1 deletion. We observed significantly higher percentages of total CD45.2 + cells as well as CD45.2 + myeloid (Gr-1 +), B- and T-cells in the peripheral blood of chimeric mice receiving Jak2 VF/+ BM compared with chimeric mice receiving IL-1R1cKO; Jak2 VF/+ BM. We also observed significantly reduced percentages of CD45.2 + LSK, LK, Gr-1 + and CD41 + cells in the BM of chimeric recipient animals receiving IL-1R1cKO; Jak2 VF/+ BM compared with Jak2 VF/+ BM. These results suggest a role of IL-1 signaling in clonal expansion of Jak2V617F mutant HSPC. Additionally, we tested the effects of blocking IL-1R1 using an anti-IL-1R1 antibody in the homozygous Jak2V617F knock-in mouse model of MF. We observed that anti-IL-1R1 antibody treatment significantly reduced peripheral blood WBC and neutrophil counts and decreased HSPC and myeloid precursors in the BM of Jak2 VF/VF mice. Furthermore, anti-IL-1R1 antibody treatment significantly reduced splenomegaly and markedly reduced BM fibrosis in Jak2 VF/VF mice, suggesting that therapies targeting IL-1R1 could be useful for the treatment of myelofibrosis. Overall, our results suggest that IL-1 signaling contributes to clonal expansion of Jak2V617F mutant HSPC and progression of bone marrow fibrosis in MPN. Disclosures No relevant conflicts of interest to declare.

The oncogenic JAK2V617F mutation has been found in a majority of patients with Philadelphia chromosome-negative myeloproliferative neoplasms (MPN) including polycythemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (PMF). Ruxolitinib, a JAK1/JAK2 inhibitor, has been approved for treatment of MF and advanced PV. Although ruxolitinib treatment can reduce splenomegaly and alleviate constitutional symptoms, it does not induce disease remission or cure bone marrow (BM) fibrosis in patients with MPN/MF. Thus, there is a critical need to identify new therapeutic target and develop novel targeted therapies for MPN/MF. We found that SHP2, a protein tyrosine phosphatase that positively regulates growth factor and cytokine signaling, is constitutively hyperphosphorylated in mouse and human MPN hematopoietic cells expressing JAK2V617F. We found that genetic ablation of SHP2 markedly inhibited the development of PV disease and BM fibrosis in Jak2V617F knock-in mouse models of MPN. So, we hypothesize that targeting of SHP2 alone or in combination with JAK2 inhibition might be useful for treatment of JAK2V617F-evoked MPN. In this study, we investigated the efficacy of SHP2 inhibition using an allosteric SHP2 inhibitor, SHP099, in hematopoietic cells and progenitors expressing JAK2V617F and a Jak2V617F knock-in mouse model of MPN. Treatment of SHP099 alone significantly reduced proliferation of murine BA/F3 cells expressing JAK2V617F. SHP099 treatment also significantly inhibited human JAK2V617F-positive UKE-1 cells. However, SHP099 only modestly affected proliferation of wild type JAK2-expressing BA/F3 cells at higher concentrations. SHP099 treatment also resulted in marked apoptosis in BA/F3-EpoR-JAK2V617F and UKE-1 cells but not in wild-type JAK2 expressing BA/F3-EpoR cells. We also found that SHP099 and ruxolitinib synergistically induced apoptosis in JAK2V617F-expressing hematopoietic cells. Furthermore, SHP099 significantly inhibited hematopoietic progenitor colony growth in MPN/MF patient CD34+ cells. We previously generated conditional Jak2V617F knock-in mice. Whereas expression of heterozygous Jak2V617F (Jak2 VF/+) induces a PV-like disease, homozygous Jak2V617F (Jak2 VF/VF) expression promotes rapid progression to myelofibrosis. We utilized heterozygous Jak2V617F mice to test the in vivo efficacy of SHP099 against PV. Treatment of SHP099 significantly reduced the increase in WBC, neutrophil and RBC counts and markedly reduced splenomegaly in heterozygous Jak2V617F (Jak2 VF/+) mice. SHP099 treatment also significantly reduced hematopoietic stem/progenitors (HSPC) and myeloid precursors (Gr-1 +/Mac1 +) in the BM and spleens of Jak2V617F mice. Erythropoietin (Epo)-independent erythroid colony formation in the BM and spleens, a hall-mark feature of PV disease, was observed in Jak2V617F mice. Treatment of SHP099 markedly inhibited the Epo-independent CFU-E colonies in the BM and spleens of heterozygous Jak2V617F mice. We also tested the efficacy of SHP099 alone or in combination with ruxolitinib against myelofibrosis using our homozygous Jak2V617F (Jak2 VF/VF) mice. SHP099 treatment alone or in combination with ruxolitinib significantly reduced WBC and neutrophil counts and markedly reduced splenomegaly in Jak2 VF/VF mice. Treatment of SHP099 or SHP099/ruxolitinib combination also significantly reduced the HSPC and myeloid precursor cells in the BM and spleens of Jak2 VF/VF mice. Histopathologic analyzes revealed extensive BM fibrosis in vehicle-treated Jak2 VF/VFmice. SHP099 treatment alone caused marked reduction of BM fibrosis in Jak2 VF/VF mice whereas combined treatment of SHP099 and ruxolitinib almost completely inhibited BM fibrosis in Jak2 VF/VF mice. Additionally, we performed competitive BM transplantation assays using Mx1Cre; Jak2 VF/VF GFP+ and WT mice BM cells followed by drug treatments. We observed that combined treatment of SHP099 and ruxolitinib significantly reduced the percentage of Jak2V617F mutant GFP+ LSK and myeloid cells in the BM of chimeric mice, suggesting that SHP099 and ruxolitinib combination preferentially inhibits oncogenic Jak2V617F mutant hematopoietic progenitors. Overall, our results suggest that SHP099 alone or in combination with ruxolitinib may have therapeutic potential against PV and MF and support the clinical investigation of SHP2 inhibitor in patients with PV/MF. Disclosures No relevant conflicts of interest to declare.

Chemically-modified antisense oligonucleotide-mediated exon-skipping has been validated as a therapeutic strategy for tackling several disease pathologies, particularly duchenne muscular dystrophy. To date, only sugar-modified and internucleotide linkage-modified oligonucleotide chemistries have been explored for exon-skipping applications. Herein, for the first time, we have investigated the potential of nucleobase-modified antisense oligonucleotides to induce exon-skipping. For this purpose, we have synthesised 5-(phenyltriazol)-2′-deoxyuridine-modified 2′-O-methyl mixmer antisense oligonucleotides, and evaluated their efficacy to induce exon-23 skipping in H-2Kb-tsA58 (H2K) mdx mouse myotubes as a model system. Our results showed that the phenyltriazol base-modified AOs successfully induced efficient exon-skipping in a DMD transcript. Our findings open up the exploration of novel base-modified antisense oligonucleotides for exon-skipping applications.

Serinol nucleic acid (SNA) is a novel nucleic acid analogue that can form highly stable heteroduplexes with complementary DNA and RNA sequences. Structurally, SNA is a close mimic to peptide nucleic acid (PNA) which is widely used in diagnostic and therapeutic applications. SNA chemistry is relatively new, and so far the scope of SNA has only been explored in improving the efficacy of small interfering RNA and for developing a highly sensitive molecular beacon for diagnostic applications. In this study, we investigated the potential of SNA-modified antisense oligonucleotide (AO) in parallel to PNA-oligo for splice-modulation in an in vitro cellular model of Duchenne muscular dystrophy (DMD). We synthesized a 20-mer SNA and PNA antisense oligonucleotide (AO) designed to induce exon-23 skipping in the mouse dystrophin gene transcript. Our results demonstrated that the SNA AO induced exon-23 skipping at all tested concentrations, whereas the corresponding PNA AO failed to induce any exon-23 skipping upon 24 hours of transfection using Lipofectin transfection reagent. Our results further expands the potential of SNA oligonucleotides in therapeutic applications.

How stem cells give rise to human interfollicular epidermis is unclear despite the crucial role the epidermis plays in barrier and appendage formation. Here we use single cell-RNA sequencing to interrogate basal stem cell heterogeneity of human interfollicular epidermis and find at least four spatially distinct stem cell populations that decorate the top and bottom of rete ridge architecture and hold transitional positions between the basal and suprabasal epidermal layers. Cell-cell communication modeling through co-variance of cognate ligand-receptor pairs indicate that the basal cell populations distinctly serve as critical signaling hubs that maintain epidermal communication. Combining pseudotime, RNA velocity, and cellular entropy analyses point to a hierarchical differentiation lineage supporting multi-stem cell interfollicular epidermal homeostasis models and suggest the “transitional” basal stem cells are stable states essential for proper stratification. Finally, alterations in differentially expressed “transitional” basal stem cell genes result in severe thinning of human skin equivalents, validating their essential role in epidermal homeostasis and reinforcing the critical nature of basal stem cell heterogeneity.

Sign Language is one of the method for non-verbal communication. It is most commonly used by deaf or dumb people who have hearing or speech problems to communicate among themselves or with normal people. Vietnamese Sign Language (VSL) is a sign language system used in the community of Vietnamese hearing impaired individuals. VSL recognition aims to develop algorithms and methods to correctly identify a sequence of produced signs and to understand their meaning in Vietnamese. However, automatic VSL recognition in video has many challenges due to the orientation of camera, hand position and movement, inter hand relation, etc. In this paper, we present some feature extraction approaches for VSL recognition includes spatial feature, scene-based feature, and especially motion-based feature. Instead of relying on a static image, we specifically capture motion information between frames in a video sequence. We evaluated the proposed framework on our acquired VSL dataset including 23 alphabets, 3 diacritic marks and 5 tones in Vietnamese language with 2D camera. Additionally, in order to gain more information of hand movement and hand position, we also used the data augmentation technique. All these helpful information would contribute to an effective VSL recognition system. The experiments achieved the satisfactory results with 86.61%. It indicates that data augmentation technique provides more information about the orientation of hand. Moreover, the combination of spatial, scene and especially motion information could help the system to be able to capture information from both single frame and from multiple frames, and thus the performance of VSL recognition system could be improved.

Facial expression recognition has been applied in many fields such as human computer interaction, patient monitoring, neurology, social robot… Although facial expression recognition has gained some encourage results, there are still many challenges such as the change of illumination, blur, etc. Especially, recognizing between sadness and anger expression raises more barriers. In this paper, we proposed a framework using only salient facial regions, but it would be able to improve the accuracy of facial expression recognition. In this framework, one of the most state-of-the-art descriptor, called Pyramid of Local Phase Quantization descriptor (PLPQ) was used to robust with respect to image blur. The experiment achieved 97.7% accuracy recognition rate on the extend Cohn-Canade (CK+) database, and outperformed than other state-of-the-art facial expression recognition methods.

Twisted intercalating nucleic acids (TINA)-modified oligonucleotides containing phenylethynylpyren-1-yl derivatives were reported to improve the thermal stability of the nucleic acid duplexes, triplexes and G-quadruplexes. In the present study, we have investigated the potential of TINA-modified antisense oligonucleotides (AOs) in splice modulation by induced exon-skipping in vitro. We used both para-TINA (p-TINA) and ortho-TINA (o-TINA)-modified 2′-O-methyl (2′-OMe) AOs on a phosphorothioate backbone (PS) designed to skip exon-23 in dystrophin pre-mRNA transcript in mdx mice myotubes. A fully-modified 2′-OMePS AO control was used in parallel. Our results showed that both p-TINA and o-TINA-modified AOs were able to induce exon-23 skipping. These results provide new insights on expanding the applicability of TINA-modified oligonucleotides.

Accurate detection of single nucleotide polymorphisms (SNPs) is paramount for the appropriate therapeutic intervention of debilitating diseases associated with SNPs. However, in some cases current nucleic acid probes fail to detect allele-specific mutations, for example, human platelet antigens, HPA-15a (TCC) and HPA-15b (TAC) alleles associated with neonatal alloimmune thrombocytopenia. Towards this, it is necessary to develop a novel assay for detection of allele-specific mutations. In this study, we investigated the potential of unlocked nucleic acid (UNA)-modified primers in SNP detection utilising an enzymatic polymerisation-based approach. Our results of primer extension and asymmetric polymerase chain reaction by KOD XL DNA polymerase revealed that UNA-modified primers achieved excellent allele-specificity in discriminating the human platelet antigen DNA template, whereas the DNA control primers were not able to differentiate between the normal and mutant alleles, demonstrating the scope of this novel UNA-based enzymatic approach as a robust methodology for efficient detection of allele-specific mismatches. Although further evaluation is required for other disease conditions, we firmly believe that our findings offer a great promise for the diagnosis of neonatal alloimmune thrombocytopenia and other SNP-related diseases.

Despite advancements in the development of high generation cationic-dendrimer systems for delivery of nucleic acid-based therapeutics, commercially available chemical agents suffer from major drawbacks such as cytotoxicity while being laborious and costly to synthesize. To overcome the aforementioned limitations, low-generation cationic peptide asymmetric dendrimers with side arm lipid (cholic and decanoic acid) conjugation were designed, synthesized and systematically screened for their ability to self-assemble into micelles using dynamic light scattering. Cytotoxicity profiling revealed that our entire asymmetric peptide dendrimer library when trialled alone, or as asymmetric dendrimer micelle-nucleic acid complexes, were non-cytotoxic across a broad concentration range. Further, the delivery efficiency of asymmetric peptide dendrimers in H-4-II-E (rat hepatoma), H2K (mdx mouse myoblast), and DAOY (human medulloblastoma) cells demonstrated that cholic acid-conjugated asymmetric dendrimers possess far superior delivery efficiency when compared to the commercial standards, Lipofectamine 2000 or Lipofectin®.

The Isochronous Mass Spectrometry (IMS) based on storage rings is a powerful technique for mass measurement of short-lived exotic nuclei. The transition energy $��_t$ of the storage ring is a vital parameter of the IMS technique. It is difficult to measure the $��_t$ and its relation to momentum spread or circulating length, especially to monitor the variation of $��_t$ during experiments. An experimental investigation on the $��_t$ has been performed for the IMS experiment at the Cooler Storage Ring of the Heavy Ion Research Facility in Lanzhou (HIRFL-CSRe). With the velocity measured by two time-of-flight (TOF) detectors, the $��_t$ as a function of orbital length can be determined. The influences of higher order magnetic field components on the $��_t$ function were inferred for isochronous correction. This paper introduces and investigates the influence of dipole magnetic fields, quadrupole magnetic fields and sextupole magnetic fields on the $��_t$ function. With the quadrupole magnets and sextupole magnets corrections, a mass resolution of 171332 (FWHM) and $��(T)/T=1.34\times10^{-6}$ were reached, which shall be compared with 31319 (FWHM) and $��(T)/T=7.35\times10^{-6}$ obtained without correction., 10 figures,19 pages

The Isochronous Mass Spectrometry (IMS) is a powerful technique developed in heavy-ion storage rings for measuring masses of very short-lived exotic nuclei. The IMS is based on the isochronous setting of the ring. One of the main parameters of this setting is the transition energy $��_{t}$. %The transition energy $��_{t}$ plays an important role in the isochronous mass spectrometry (IMS). It has been a challenge to determine the $��_{t}$ and especially to monitor the variation of $��_{t}$ during experiments. In this paper we introduce a method to measure the $��_{t}$ online during IMS experiments by using the acquired experimental data. Furthermore, since the storage ring has (in our context) a relatively large momentum acceptance, the variation of the $��_{t}$ across the ring acceptance is a source of systematic uncertainty of measured masses. With the installation of two time-of-flight (TOF) detectors, the velocity of each stored ion and its revolution time are simultaneously available for the analysis. These quantities enabled us to determine the $��_{t}$ as a function of orbital length in the ring. The presented method is especially important for future IMS experiments planned at the new-generation storage ring facilities FAIR in Germany and HIAF in China., 7 pages

Stress conditions, such as a block in fatty acid synthesis, signal bacterial cells to exit the cell cycle. Caulobacter crescentus FabH is a cell-cycle-regulated β-ketoacyl-acyl carrier protein synthase that initiates lipid biosynthesis and is essential for growth in rich media. To explore how C. crescentus responds to a block in lipid biosynthesis, we created a FabH-depletion strain. We found that FabH depletion blocks lipid biosynthesis in rich media and causes a cell cycle arrest that requires the alarmone (p)ppGpp for adaptation. Notably, basal levels of (p)ppGpp coordinate both a reduction in cell volume and a block in the over-initiation of DNA replication in response to FabH depletion. The gene ctrA encodes a master transcription factor that directly regulates 95 cell-cycle-controlled genes while also functioning to inhibit the initiation of DNA replication. Here, we demonstrate that ctrA transcription is (p)ppGpp-dependent during fatty acid starvation. CtrA fails to accumulate when FabH is depleted in the absence of (p)ppGpp due to a substantial reduction in ctrA transcription. The (p)ppGpp-dependent maintenance of ctrA transcription during fatty acid starvation initiated from only one of the two ctrA promoters. In the absence of (p)ppGpp, the majority of FabH-depleted cells enter a viable but non-culturable state, with multiple chromosomes, and are unable to recover from the miscoordination of cell cycle events. Thus, basal levels of (p)ppGpp facilitate C. crescentus' re-entry into the cell cycle after termination of fatty acid starvation.

Urethral injury in females is rare in the absence of pelvic fracture. We report a case of a five year-old girl who sustained sharp perineal trauma that resulted in complete transection of both the vagina and urethra. We discuss management and review the literature.

Aptamers are short synthetic DNA or RNA oligonucleotides that adopt secondary and tertiary conformations based on Watson–Crick base-pairing interactions and can be used to target a range of different molecules. Two aptamers, HD1 and HD22, that bind to exosites I and II of the human thrombin molecule, respectively, have been extensively studied due to their anticoagulant potentials. However, a fundamental issue preventing the clinical translation of many aptamers is degradation by nucleases and reduced pharmacokinetic properties requiring higher dosing regimens more often. In this study, we have chemically modified the design of previously described thrombin binding aptamers targeting exosites I, HD1, and exosite II, HD22. The individual aptamers were first modified with an inverted deoxythymidine nucleotide, and then constructed bivalent aptamers by connecting the HD1 and HD22 aptamers either through a triethylene glycol (TEG) linkage or four consecutive deoxythymidines together with an inverted deoxythymidine nucleotide at the 3′-end. The anticoagulation potential, the reversal of coagulation with different antidote sequences, and the nuclease stability of the aptamers were then investigated. The results showed that a bivalent aptamer RNV220 containing an inverted deoxythymidine and a TEG linkage chemistry significantly enhanced the anticoagulation properties in blood plasma and nuclease stability compared to the existing aptamer designs. Furthermore, a bivalent antidote sequence RNV220AD efficiently reversed the anticoagulation effect of RNV220 in blood plasma. Based on our results, we believe that RNV220 could be developed as a potential anticoagulant therapeutic molecule.

Laboratory-evolved RNAs bind a wide variety of targets and serve highly diverse functions, including as diagnostic and therapeutic aptamers. The majority of aptamers have been identified using in vitro selection (SELEX), a molecular evolution technique based on selecting target-binding RNAs from highly diverse pools through serial rounds of enrichment and amplification. In vitro selection typically yields multiple distinct motifs of highly variable abundance and target-binding affinities. The discovery of new aptamers is often limited by the difficulty of characterizing the selected motifs, because testing of individual sequences tends to be a tedious process. To facilitate the discovery of new aptamers within in vitro selected pools, we developed Apta-Seq, a multiplex analysis based on quantitative, ligand-dependent 2' acylation of solvent-accessible regions of the selected RNA pools, followed by reverse transcription (SHAPE) and deep sequencing. The method reveals, in a single sequencing experiment, the identity, structural features, and target dissociation constants for aptamers present in the selected pool. Application of Apta-Seq to a human genomic pool enriched for ATP-binding RNAs yielded three new aptamers, which together with previously identified human aptamers suggest that ligand-binding RNAs may be common in mammals.

Background Mayer-Rokitansky-Kuster-Hauser (MRKH) syndrome is a congenital condition characterized by aplasia of the vagina with or without concurrent uterine and/or cervical aplasia. Type II (MURCS) is a rare form involving MUllerian agenesis, Renal agenesis, and Cervicothoracic Somite anomalies. Case A 17-yr-old virginal female presented for evaluation of primary amenorrhea and pelvic pain. Her medical history was significant for a bicuspid aortic valve and right radial dysplasia. She demonstrated normal secondary sexual development and a normal karyotype. Pelvic magnetic resonance imaging revealed an aplastic vaginal, no identifiable cervix or uterus, and normal ovaries. A laparoscopy was performed for the evaluation of pain and findings were significant for bilateral uterine horn and fallopian tube remnants noted along the pelvic sidewalls. This patient evaluation suggests a unique presentation of MURCS association. Conclusion To our knowledge, this is the first case of MRKH presenting with a bicuspid aortic valve and radial dysplasia. A review of the literature reveals no other cases of MRKH with these unique anomalies.

Integrin alpha-4 (ITGA4) is a validated therapeutic target for multiple sclerosis (MS) and Natalizumab, an antibody targeting ITGA4 is currently approved for treating MS. However, there are severe side effects related to this therapy. In this study, we report the development of a novel DNAzyme that can efficiently cleave the ITGA4 transcript. We designed a range of DNAzyme candidates across various exons of ITGA4. RNV143, a 30mer arm-loop-arm type DNAzyme efficiently cleaved 84% of the ITGA4 mRNA in human primary fibroblasts. RNV143 was then systematically modified by increasing the arm lengths on both sides of the DNAzymes by one, two and three nucleotides each, and incorporating chemical modifications such as inverted-dT, phosphorothioate backbone and LNA-nucleotides. Increasing the arm length of DNAzyme RNV143 did not improve the efficiency however, an inverted-dT modification provided the most resistance to 3′ → 5′ exonuclease compared to other modifications tested. Our results show that RNV143A could be a potential therapeutic nucleic acid drug molecule towards the treatment for MS.

 Abstract—Nowadays, the large datasets become more and more common. However, traditional visualization techniques, which although allow to visually analyze and explore data, can not scale well with the large one. This restrains the ability of detecting, recognizing and classifying phenomena of interest, such as patterns, clusters, trends, etc. This Paper proposes a method for interactive multi-resolution visualization to overcome the problem of traditional visualization techniques when working with a large dataset via hierarchical clustering. Based on hierarchical clustering, users can not only examine the dataset at different levels of detail, but also can explore many regions of interest. The basic idea underlying this method is to choose multiple scales from the hierarchical tree for representing the data at different levels of abstraction, which creates an easy environment for interactive exploration without re-run the clustering algorithm. Moreover, we also define a criterion for evaluating the multiple scale representation based on the concept of split factor. An experiment of applying the proposed method into the task of interactive visualization in a clinical case study of the large dMRI (diffusion magnetic resonance imaging) data is also carried out. The results show that our proposed method efficiently provides a friendly tool for visualization the large data.

Antisense oligonucleotide (AO) mediated exon skipping has been widely explored as a therapeutic strategy for several diseases, in particular, for rare genetic disorders such as Duchenne muscular dystrophy (DMD). To date, the potential of anhydrohexitol nucleic acid (HNA), cyclohexenyl nucleic acid (CeNA) and altritol nucleic acid (ANA) has not been explored in exon skipping. For the first time, in this study we designed and synthesised HNA, CeNA and ANA-modified 2′-O-methyl (2′-OMe) mixmer AOs on a phosphorothioate (PS) backbone, and evaluated their potential to induce exon 23 skipping in mdx mouse myotubes, as a model system. Our results clearly showed that all three AO candidates modified with HNA, CeNA and ANA could efficiently induce Dmd exon 23 skipping in vitro in parallel to the fully modified 2′-OMePS AO with reduced dual exon 22/23 skipping. In addition, they showed high nuclease resistance and no cytotoxicity compared to the 2′-OMePS AO, demonstrating the applicability of HNA, CeNA and ANA nucleotide-modified AOs in exon skipping.

Podocyte, the gatekeeper of the glomerular filtration barrier, is a primary target for growth factor and Ca

We report the results of our long-term monitoring study of cirrus clouds using our locally developed lidar sytem located in Hanoi, Vietnam (21.03°N, 105.85°E). Our data, spanning the period from 2011 to 2017, show that the cirrus clouds above Hanoi are generally found between 6.7 and 18.0 km with a mean height of 14.0 km. The cloud thickness is estimated to vary between 0.2 and 7.0 km with an average thickness of 2.3 ± 1.2 km. We also derive an average optical depth of 0.32 ± 0.22 and an average lidar ratio 30 ± 18. We also compare the geometrical and optical properties of cirrus clouds above Hanoi, where until now lidar study is still lacking, with that obtained for other locations in Asia and around the world.

Harmful algal blooms (HABs) are a serious environmental problem globally. The ability of cyanobacteria, one of the major causative agents of HABs, to grow in heavy metal polluted areas is proving a challenge to environmental restoration initiatives. Some cyanobacteria secrete toxins, such as microcystin, that are potentially dangerous to animals and humans. In this study, the physiology of a cyanobacterium was assessed to nickel chloride exposure. Cell growths were monitored throughout the study with various nickel chloride concentrations (0, 10, 25 or 50 mg/L). Morphological abnormalities were observed with microscopic image analyses. Inductively coupled plasma mass spectrometry (ICP-MS) was carried out to trace the distribution of nickel during the growth period. This study provides insight on potential nickel response mechanisms in freshwater cyanobacteria, which may lead to effective HAB prevention strategy development.

Masses of ^{52g,52m}Co were measured for the first time with an accuracy of ∼10 keV, an unprecedented precision reached for short-lived nuclei in the isochronous mass spectrometry. Combining our results with the previous β-γ measurements of ^{52}Ni, the T=2, J^{π}=0^{+} isobaric analog state (IAS) in ^{52}Co was newly assigned, questioning the conventional identification of IASs from the β-delayed proton emissions. Using our energy of the IAS in ^{52}Co, the masses of the T=2 multiplet fit well into the isobaric multiplet mass equation. We find that the IAS in ^{52}Co decays predominantly via γ transitions while the proton emission is negligibly small. According to our large-scale shell model calculations, this phenomenon has been interpreted to be due to very low isospin mixing in the IAS.

Masses of $^{52g,52m}$Co were measured for the first time with an accuracy of $\sim 10$ keV, an unprecedented precision reached for short-lived nuclei in the isochronous mass spectrometry. Combining our results with the previous $��$-$��$ measurements of $^{52}$Ni, the $T=2$, $J^��=0^+$ isobaric analog state (IAS) in $^{52}$Co was newly assigned, questioning the conventional identification of IASs from the $��$-delayed proton emissions. Using our energy of the IAS in $^{52}$Co, the masses of the $T=2$ multiplet fit well into the Isobaric Multiplet Mass Equation. We find that the IAS in $^{52}$Co decays predominantly via $��$ transitions while the proton emission is negligibly small. According to our large-scale shell model calculations, this phenomenon has been interpreted to be due to very low isospin mixing in the IAS., Accepted for publication in PRL. 5 pages, 2figures

The compound 5, containing the novel heterocycle 2-oxa-4,7-diazabicyclo[3.3.1]non-3-ene, has been obtained in a synthetic approach toward oxazoles and 1,3-diazepanes of natural product-like complexity from cyclization and rearrangement of δ-lactam cyanamides. When this procedure was applied to a silyl-protected N-((3S,4S,5S)-4,5-dihydroxy-2-oxopiperidin-3-yl)cyanamide (2b) formation of the novel heterobicyclic scaffold 5 was observed along with the expected oxazole (3b) and diazepane (4b) products. The crystal structures of 5 and diazepane 4b are described. Compound 5 crystallized from methanol in the monoclinic system, P21 space group with unit cell parameters a = 15.3402(9), b = 7.2717(4), c = 22.5803(13), β = 106.8620(10) and a cell volume of 2410.5(2) A3. The synthesis and crystal structure of the title compound is described.

Informed consent is an integral part of the preoperative counseling process. It is important that we know the best way to relay this information to patients undergoing surgery, specifically, hysterectomy.We sought to determine whether supplementing normal physician counseling with a video presentation improves patient comprehension during the informed consent process for hysterectomy.In a randomized, mixed factorial controlled trial, standard physician counseling (control arm) was compared to physician counseling plus video presentation (video arm) during the prehysterectomy informed consent process. Primary outcome was improvement in patient comprehension measured by assessments at baseline, postcounseling, day of surgery, and postsurgery. Patient satisfaction was measured by a validated questionnaire. Audiotaped patient-physician interactions were analyzed to determine time spent counseling, number of patient questions, and whether standard counseling included 11 predetermined critical components included in the video. A sample size of 60 per group (N = 120) was planned to compare both groups.From May 2014 through June 2015, 120 patients were enrolled and 116 randomized: 59 to the video arm and 57 to the control arm. All characteristics were similar between groups. Video arm subjects demonstrated greater improvement in comprehension scores in both postcounseling (9.9% improvement; 95% confidence interval, 4.2-15.7%; P = .0009) and day-of-surgery questionnaires (7.2% improvement; 95% confidence interval, 0.96-13.4%; P = .02). Scores 4-6 weeks after surgery returned to baseline for both groups. Control subjects were less likely to be counseled about risk of thrombosis (P.0001), colostomy (P.0001), further medical/surgical therapy (P = .002), hormone replacement therapy (P.0001), or postoperative expectations (P.0001). Physicians spent more time counseling patients who did not watch the video (8 vs 12 minutes, P = .003) but number of questions asked by patients in each group was similar.Enhancing prehysterectomy counseling with a video improves patient comprehension through day of surgery, increases thoroughness of counseling, and reduces physician time.

Purpose To evaluate the efficacy and safety of 0.1 mmol/kg gadodiamide administration for contrast-enhanced magnetic resonance angiography (CE-MRA) in detecting hemodynamically relevant main stenosis (ie, ≥50% or occlusion) of aortoiliac arteries. Materials and Methods In a multicenter, phase 3, controlled study, patients with suspected or proven peripheral arterial occlusive disease (PAOD) underwent CE-MRA with administration of gadodiamide. Intraarterial digital subtraction angiography (IA-DSA) was used as the reference. The study was approved by all Institutional Review Boards or Institutional Ethic Committees prior to commencement of patient recruitment and written informed consent was obtained from all patients. Results Independent readers rated 25%–45% of CE-MRA images as excellent compared with 0.3%–6% of noncontrast MRA images. Mean imaging acquisition time for CE-MRA was

To evaluate the ability to create in vivo antegrade fenestrations (IVAF) using a radiofrequency probe in juxtarenal aortic stent-grafts to preserve the patency of renal arteries.Modified stent-grafts with an unsupported fenestration area were deployed in the juxtarenal aorta of 2 25-kg dogs. Prior to deployment, both renal arteries were marked with detachable coils that were later removed (dog 1) or with hydrophilic catheters (dog 2). After deployment, a radiofrequency probe was used to perforate the graft. If puncture was successful, attempts were made to pass guidewires into the renal arteries for balloon dilation and stenting of the graft perforation. Doppler ultrasound scans of the renal arteries were taken after 1 week. Doppler ultrasound and angiography were repeated prior to autopsy and macroscopic analysis at 1 month.Fenestration was attempted in 3 renal arteries (1 in dog 1 and 2 in dog 2). It was successful in 2 renal arteries but required 6 attempts in dog 1 and 3 in dog 2. The failed case was related to the position of a stent-graft strut close to the fenestration area. One stent thrombosis was seen during follow-up, while the other fenestrated artery remained patent. No stent fracture was encountered during follow-up.This radiofrequency device allowed successful fenestration but was difficult to control. Technical improvements are required to improve clinical success and patency.