tbuckley/cabot-search huggingface dataset:
RDEB 中的 miR‐145‐5p 促纤维化活性
Authors: A.G. Condorelli, E. Logli, F. Cianfarani, M. Teson, A. Diociaiuti, M. El Hachem, G. Zambruno, D. Castiglia, T. Odorisio
Journal: British Journal of Dermatology (2019)

隐性营养不良性大疱性表皮松解症(RDEB)是一种罕见且致残性极高的遗传疾病。RDEB 的标志是皮肤脆弱、持续起疱以及伤口愈合不良,从而导致炎症和纤维化,这意味着组织变硬。纤维化是 RDEB 的主要并发症(包括肢体畸形和癌症)的潜在机制,而预防它是改善疾病进程的策略。尽管已鉴定出在 RDEB 纤维化过程中失控的几种分子,但其发病机理尚未完全明确。我们的遗传密码包含产生 RNA 分子(称为信使 RNA)的信息,这些 RNA 分子可用于构建形成人体的蛋白质。但是,一大类 RNA 分子(称为 microRNA)不会转化为蛋白质,而是调节所产生的蛋白质数量。microRNA 的功能改变导致许多疾病的发展。本研究在意大利 Bambino Gesù 儿童医院进行,旨在识别和鉴定 RDEB 患者中改变并导致其皮肤纤维化的 microRNA 的作用。这项实验室研究使用了一种细胞类型,即成纤维细胞,该细胞遍布皮肤,并且是纤维化的主要参与者。作者观察到,与健康个体的细胞相比,从 RDEB 患者获得的成纤维细胞中某些 microRNA 含量更高,并证明其中之一,miR‐145‐5p 促进了纤维化。研究人员关闭了 RDEB 成纤维细胞中的 miR‐145‐5p,然后研究了成纤维细胞收缩、增殖和移动的能力,这些都是纤维化过程中增加的活性。阻断 miR‐145‐5p 可减少 RDEB 成纤维细胞的收缩、增殖和迁移能力,并可确定各种收缩性和促纤维化(引起纤维化)分子的减少。总之,作者发现了一种可促使 RDEB 中纤维化的发展的新的 microRNA,并描述了其作用方式。这些结果有助于我们进一步了解该疾病以及未来治疗的可能目标。
Unexpected Concomitance of BCR-ABL and PML-Rarα Leukemia - Three-Year Follow-up
Authors: Caique Pereira de Moura Martins, João Vítor Ternes Rech, Lee I-Ching, Giovanna Steffenello Durigon, Joanita Angela Del Moral, Mirella Rodrigues Oliveira, Bruno Vieira Dias, Maria Claudia Santos, Andressa Oliveira Martin Wagner, André Guedes Vieira
Journal: Blood (2019)
TMIC-32. PARALLEL SINGLE CELL NUCLEOSOME OCCUPANCY AND RNA SEQUENCING ON RECURRENT GBM
Authors: Jack Shireman, Eric Gauchat, Heather Eckart, Cheol Park, Anindita Basu, Sebastian Pott, Atique Ahmed
Journal: Neuro-Oncology (2019)

Abstract Nearly all patients diagnosed with Glioblastoma (GBM) will experience a fatal recurrence of the tumor. Thought to be in part driven by immense tumor heterogeneity it is important to explore the small subpopulations of tumor cells with in depth single cell sequencing pre and post therapy in order to understand recurrence. To this end, we created an experimental in vivo pipeline that allows us profile not only gene expression changes during therapy, but also epigenetic shifts due to methylation across the genome at the single cell level from a single tumor. Single Cell NomE-Seq libraries were created and correctly identified characteristic CTCF binding regions within DNase1 hypersensitivity regions when compared back to representative encode data sets. Primary tumors analyzed by single cell RNA sequencing showed enrichment for on average 5 significant principle components (St. Dev &gt;2 verified by Elbow Plot). Comparatively, recurrent temozolomide (TMZ) exposed tumors averaged 10 significant principle components (St. Dev &gt;2 verified by Elbow Plot) suggesting TMZ therapy causes tumors to diversify their gene expression profiles. For direct comparison samples were merged into a continuous data set and dimensional analysis with TSNE reduction (15 dimensions used) identified 6 unique clusters, with one cluster being over-represented by cells from recurrent, TMZ exposed mice. Gene Ontology analysis on expression values contained within in this cluster demonstrated significant enrichment for ribosome biogenesis/ribosomal structure, (p=2.87e-17) and mRNA catabolic processes (p=2.47e-30). Further, comparison to a similar data set gathered using cells in vitro culture conditions demonstrates superior intraturmoral heterogeneity from cells isolated freshly from the brains of mice as opposed to tissue culture, indicating the effectiveness of our model for assaying heterogeneity. Ultimately, these data illuminate possible new mechanisms for TMZ induced ribosomal modifications underlying intraturmoral heterogeneity in GBM and provide an expandable technique for further experimentation.
Integrating Touchscreen-Based Geriatric Assessment and Frailty Screening for Adults with Multiple Myeloma to Drive Personalized Treatment Decisions
Authors: Nitya Nathwani, Supriya G. Mohile, Sandra Kurtin, Debra Wujcik, Susie Owenby, Matthew Dudley, William Dudley, Tanya M. Wildes
Journal: Blood (2019)
Prevention of Rh-haemolytic disease.
Authors: S Murray
Journal: BMJ (1967)

MtC-.YOW& titioner palpated an epigastric mass.On admis- sion the child appeared well.He was afebrile and the pulse rate was normal.The abdomen was soft and the presence of a mass was not confirmed.Rectal examination was negative, and plain x-rays of the abdomen showed no evidence of fluid levels or dilated loops of bowel.He was therefore observed for 24 hours, after which time he complained of further abdominal pain.Examination during a spasm of pain confirmed the presence of a tender sausage-shaped mass in the epigastrium.A diagnosis of intussusception was made, and an immediate barium enema performed, which con- firmed this.The apex lay in the epigastrium.This was readily reduced by the pressure from the enema, and filling was obtained to the caecum.No barium entered the terminal ileum, and a filling defect was demonstrated in the ileocaccal region (Fig. 1).It was not possible to be certain, therefore, that reduction had been complete.
Erythropoietin Is Associated with a Decline in the iFGF23/cFGF23 Ratio in Patients with Various Hereditary Hemolytic Anemias
Authors: Annelies J. Van Vuren, Michele F. Eisenga, Stephanie van Straaten, Andreas Glenthøj, Carlo A.J.M. Gaillard, Stephan J.L. Bakker, Martin H. de Borst, Richard van Wijk, Eduard J. van Beers
Journal: Blood (2019)
TMOD-19. ELUCIDATING THE RESISTANCE TO IMMUNOTHERAPY IN BRAIN TUMORS USING A HUMANIZED MICROBIOME MOUSE MODEL
Authors: Kory Dees, Hyunmin Koo, Joseph Hakim, J Fraser Humphreys, David Crossman, Michael Crowley, Louis Nabors, Etty Benveniste, Casey Morrow, Braden McFarland
Journal: Neuro-Oncology (2019)

Abstract Although the immunotherapy anti-PD-1 works well in glioblastoma (GBM) pre-clinical mouse models, the therapy has not demonstrated a similar efficacy in patient clinical trials. Recent studies have linked the gut microbe composition to tumor growth and response to immunotherapy in some cancers. To date, all GBM pre-clinical studies have been done in mouse models using mouse gut microbiomes. There are significant differences between mouse and human microbial gut compositions, with up to 85% of gut bacteria found in laboratory mice not found in humans. Because it is known that the gut microbe composition can impact the immune system, we hypothesize that the non-responsiveness of GBM patients to immunotherapy may be due to the composition of the gut microbiome. Therefore, we have generated a humanized microbiome mouse model in which mice have been colonized by human donor microbes in their GI tract (two different healthy human donors (HuM1 and HuM2)). In preliminary results, we have found that HuM1 mice are resistant to anti-PD-1, while HuM2 mice are responders to anti-PD-1 in the GL261 syngeneic intracranial model. These mice are genetically identical and only differ in gut microbiome composition. Furthermore, we found that HuM2 mice exhibited a significant increase in cytotoxic CD8+T-cells producing IFN-γ and significant increased CD8+/Treg ratio in the spleen following anti-PD-1 treatment, which was not observed in the HuM1 mice. When testing the efficacy of standard of care temozolomide (TMZ) in our humanized mice, we found that TMZ significantly prolonged survival of both HuM1 and HuM2 mice with intracranial tumors. However, HuM2 mice exhibited superior efficacy (p&lt; 0.001; 57% survival), compared to HuM1 mice (p&lt; 0.01; 0% survival). We are extending these studies to analyze additional humanized microbiome lines as well as GBM patient donor lines to more accurately understand individual responses to tumor growth and responsiveness to therapies.
Topically applied treatments for external genital warts in nonimmunocompromised patients: a systematic review and network meta‐analysis
Authors: J.M. Jung, C.J. Jung, W.J. Lee, C.H. Won, M.W. Lee, J.H. Choi, S.E. Chang
Journal: British Journal of Dermatology (2019)

Selecting a topical treatment from among the numerous topical agents for external genital warts remains challenging without clear evidence. Our aim was to evaluate comparatively the efficacy and safety of topical agents for external genital warts using a network meta‐analysis. We included all randomized controlled trials that evaluated any topically applied treatment for external genital warts. Using the R package netmeta, network meta‐analyses were performed with a frequentist approach. We identified 41 relevant studies comprising 6371 patients. Among conventional agents, podophyllotoxin 0·5% solution (odds ratio 1·94, 95% confidence interval 1·02–3·71) was significantly more efficacious than imiquimod 5% cream for lesion clearance; however, it was associated with a higher overall adverse event rate. Sinecatechins 15% ointment (odds ratio 0·21, 95% confidence interval 0·12–0·34) was significantly less efficacious than imiquimod 5% cream. Idoxuridine, polyhexamethylene biguanide, cidofovir and SB206 showed comparable therapeutic efficacies with conventional therapies. None of the treatments were significantly different from each other with respect to recurrence, patients with severe adverse events, or patients who withdrew because of treatment‐related adverse events. Conventional modalities were efficacious and well tolerated, although each of them had their advantages and disadvantages. Additional efficacy and safety studies are warranted for unconventional agents.
STEM-10. BIDIRECTIONAL INTERACTION BETWEEN TUMOR-ASSOCIATED PLATELETS AND GLIOMA STEM CELLS IN GLIOBLASTOMA MULTIFORME
Authors: Alankrita Raghavan, Christine Lee-Poturalski, John Willis, Amber Kerstetter-Fogle, Peggy Harris, Jeremy Rich, Michael Vogelbaum, Eckhard Jankowsky, Andrew Sloan
Journal: Neuro-Oncology (2019)

Abstract Glioblastoma Multiforme (GBM) is the most common and lethal malignant primary adult brain tumor. Therapy resistance and tumor recurrence in GBM have been attributed to glioma stem cells (GSCs), which are found in hypoxic but perivascular niches. We hypothesized that the clinically documented and prognostically relevant increase in platelets in GBM promotes formation of functional hypoxic but perivascular niches that support GSCs due to formation of intravascular thromboses, a hallmark of GBM. Our preliminary in silico analysis from TCGA GBM samples indicates significant correlation of platelet and stemness signature expression (P &lt; 0.001). High expression of platelet gene signatures also inversely correlates with overall survival in GBM patients (P &lt; 0.02). Furthermore, we found significant co-localization of known platelet and stemness markers in primary GBM specimens, supporting our hypothesis and motivating further interrogation of GSC-platelet crosstalk. Our preliminary data suggest that GSCs exposed to either tumor or healthy platelets demonstrate increased self-renewal and stemness, as determined by a significant increase in OCT4, NANOG, and OLIG2 expression compared to unexposed GSCs. This increase in stemness and self-renewal markers was not seen in platelet-exposed differentiated glioma cell (DGC) counterparts. Conversely, platelets are stimulated by GSCs and GSC-conditioned media while DGCs elicit no stimulatory effects as measured by ATP release and aggregation assays. Our results implicate a functional role for platelet-GSC interactions in the maintenance of tumor cellular hierarchy that ultimately contributes to poor clinical outcomes in GBM. RNA-Seq of platelet-privileged GSCs is currently underway to elucidate the mechanism by which platelets impact GSC self-renewal. Successful characterization of potential crosstalk between platelets and GSCs may offer new clinical perspectives into GBM and inform development of a novel treatment paradigm to target these specific cell-to-cell interactions.
Differences in delta virus hepatitis diagnosis methods and its effect on the hepatitis D prevalence
Authors: Dan-Ting Shen, Hemant Goyal, Hua-Guo Xu
Journal: Gut (2019)

We thank H Wedemeyer and F Negro for their critical commentary about our article.1 The authors acknowledge that the global disease burden of hepatitis D virus (HDV) is higher than previously estimated. However, they emphasised limitation of this systematic review and meta-analysis that about one-third of anti-HDV-positive patients can have undetectable HDV RNA levels and the global disease burden estimated by only anti-HDV-positivity rate might not reflect the true prevalence of HDV.2 We agree with the authors that synchronous detection of anti-HDV antibodies and HDV RNA is necessary to diagnose the …
Stem Cell Factor-Inducible MITF-M Expression in Therapeutics for Acquired Skin Hyperpigmentation
Authors: Cheong-Yong Yun, Eunmiri Roh, Song-Hee Kim, Jinhe Han, Jiyeon Lee, Da-Eun Jung, Ga Hyeon Kim, Sang-Hun Jung, Won-Jea Cho, Sang-Bae Han, Youngsoo Kim
Journal: Theranostics (2019)

Rationale: Microphthalmia-associated transcription factor M (MITF-M) plays important roles in the pigment production, differentiation and survival of melanocytes.Stem cell factor (SCF) and its receptor KIT stimulate MITF-M activity via phosphorylation at the post-translation level.However, the phosphorylation shortens half-life of MITF-M protein over the course of minutes.Here, we investigated novel hypotheses of (i) whether SCF/KIT can regulate MITF-M activity through gene expression as the alternative process, and (ii) whether chemical inhibition of KIT activity can mitigate the acquired pigmentation in skin by targeting the expression of MITF-M.Methods: We employed melanocyte cultures in vitro and pigmented skin samples in vivo, and applied immunoblotting, RT-PCR, siRNA-based gene knockdown and confocal microscopy.Results: The protein and mRNA levels of MITF-M in epidermal melanocytes and the promoter activity of MITF-M in B16-F0 melanoma cells demonstrated that SCF/KIT could trigger the expression of MITF-M de novo, following the phosphorylation-dependent proteolysis of pre-existing MITF-M protein.SCF/KIT regulated the transcription abilities of cAMP-responsive element-binding protein (CREB), CREB-regulated co-activator 1 (CRTC1) and SRY-related HMG-box 10 (SOX10) but not β-catenin at the MITF-M promoter.Meanwhile, chemical inhibition of KIT activity abolished SCF-induced melanin production in epidermal melanocyte cultures, as well as protected the skin from UV-B-induced hyperpigmentation in HRM2 mice or brownish guinea pigs, in which it down-regulated the expression of MITF-M de novo at the promoter level. Conclusion:We propose the targeting of SCF/KIT-inducible MITF-M expression as a strategy in the therapeutics for acquired pigmentary disorders.
Physiological levels of the PTEN-PI3K-AKT axis activity are required for maintenance of Burkitt lymphoma
Authors: Franziska Gehringer, Stephanie Ellen Weissinger, Peter Möller, Thomas Wirth, Alexey Ushmorov
Journal: Leukemia (2019)

Abstract In addition to oncogenic MYC translocations, Burkitt lymphoma (BL) depends on the germinal centre (GC) dark zone (DZ) B cell survival and proliferation programme, which is characterized by relatively low PI3K-AKT activity. Paradoxically, PI3K-AKT activation facilitates MYC-driven lymphomagenesis in mice, and it has been proposed that PI3K-AKT activation is essential for BL. Here we show that the PI3K-AKT activity in primary BLs and BL cell lines does not exceed that of human non-neoplastic tonsillar GC DZ B cells. BLs were not sensitive to AKT1 knockdown, which induced massive cell death in pAKT high DLBCL cell lines. Likewise, BL cell lines show low sensitivity to pan-AKT inhibitors. Moreover, hyper-activation of the PI3K-AKT pathway by overexpression of a constitutively active version of AKT (myrAKT) or knockdown of PTEN repressed the growth of BL cell lines. This was associated with increased AKT phosphorylation, NF-κB activation, and downregulation of DZ genes including the proto-oncogene MYB and the DZ marker CXCR4. In contrast to GCB-DLBCL, PTEN overexpression was tolerated by BL cell lines. We conclude that the molecular mechanisms instrumental to guarantee the survival of normal DZ B cells, including the tight regulation of the PTEN-PI3K-AKT axis, also operate in the survival/proliferation of BL.
Outcomes in Patients with Acute Myeloid Leukemia with Myelodysplasia-Related Changes (AML-MRC) Who Achieved Remission with CPX-351 Versus 7+3: Phase 3 Exploratory Analysis
Authors: Daniel H. Ryan, Laura F. Newell, Ellen K. Ritchie, Stephen A. Strickland, Donna E. Hogge, Scott R. Solomon, Richard M. Stone, Gary J. Schiller, Matthew J. Wieduwilt, Robert J. Ryan, Stefan Faderl, Jorge E. Cortes
Journal: Blood (2019)
INNV-35. INTRODUCING THE EDUCATIONAL NEURO-ONCOLOGY APP
Authors: Iyad Alnahhas
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND The purpose of the Neuro-Oncology Trials App is to promote evidence-based practice in neuro-oncology and educate learners about the clinical trials that have been completed in the field. Evidence-based practice means consulting the literature when treating patients and applying the results of well-designed clinical trials to questions that we encounter in clinical practice. Being well versed in the literature is essential for high-quality patient care. METHODS We have developed a reference tool in the form of a smartphone app to provide easily-searched, easy-to-read detailed summaries of the methodology and results of selected pivotal clinical trials in the field of neuro-oncology. RESULTS The Neuro-Oncology Trials App includes summaries of select published clinical trials in the field of neuro-oncology. The topics include newly diagnosed glioblastoma, recurrent glioblastoma, low-grade gliomas, primary central nervous system lymphoma and management of gliomas in the elderly. The app includes an intuitive search function that facilitates looking up trials by: tumor histology, names of authors, names of journals, names of chemotherapy medications and acronyms of names of trials. Finally, it is continually updated and made available free of charge to users. CONCLUSIONS The Neuro-Oncology Trials App is ideal for practitioners at all levels and learners (medical students, residents and fellows) to look up information and quick summaries of trials in neuro-oncology when seeing patients in clinics or during rounds. The Neuro-Oncology App is soon to be available on the Apple and Android stores.
Efficacy and Safety of Dapagliflozin in Heart Failure With Reduced Ejection Fraction According to Age
Authors: Felipe A. Martinez, Matteo Serenelli, Jose C. Nicolau, Mark C. Petrie, Chern-En Chiang, Sergey Tereshchenko, Scott D. Solomon, Silvio E. Inzucchi, Lars Køber, Mikhail N. Kosiborod, Piotr Ponikowski, Marc S. Sabatine, David L. DeMets, Monika Dutkiewicz-Piasecka, Olof Bengtsson, Mikaela Sjöstrand, Anna Maria Langkilde, Pardeep S. Jhund, John J.V. McMurray
Journal: Circulation (2019)

Background: The DAPA-HF trial (Dapagliflozin and Prevention of Adverse-Outcomes in Heart Failure) showed that dapagliflozin added to other guideline-recommended therapies reduced the risk of mortality and heart failure hospitalization and improved symptoms in patients with heart failure and reduced ejection fraction. We examined the effects of dapagliflozin according to age, given potential concerns about the efficacy and safety of therapies in the elderly. Methods: Patients in New York Heart Association functional class II or greater with a left ventricular ejection fraction ≤40% and a modest elevation of NT-proBNP (N-terminal pro-B-type natriuretic peptide) were eligible. Key exclusion criteria included systolic blood pressure &lt;95 mm Hg and estimated glomerular filtration rate &lt;30 mL·min −1 ·1.73 m −2 . The primary outcome was the composite of an episode of worsening heart failure (heart failure hospitalization or urgent heart failure visit) or cardiovascular death, whichever occurred first. Results: A total of 4744 patients 22 to 94 years of age (mean age, 66.3 [SD 10.9] years) were randomized: 636 patients (13.4%) were &lt;55 years of age, 1242 (26.2%) were 55 to 64 years of age, 1717 (36.2%) were 65 to 74 years of age, and 1149 (24.2%) were ≥75 years of age. The rate of the primary outcome (per 100 person-years, placebo arm) in each age group was 13.6 (95% CI, 10.4–17.9), 15.7 (95% CI, 13.2–18.7), 15.1 (95% CI, 13.1–17.5), and 18.0 (95% CI, 15.2–21.4) with corresponding dapagliflozin/placebo hazard ratios of 0.87 (95% CI, 0.60–1.28), 0.71 (95% CI, 0.55–0.93), 0.76 (95% CI, 0.61–0.95), and 0.68 (95% CI, 0.53–0.88; P for interaction=0.76). Consistent benefits were observed for the components of the primary outcome, all-cause mortality, and symptoms. Although adverse events and study drug discontinuation increased with age, neither was significantly more common with dapagliflozin in any age group. Conclusions: Dapagliflozin reduced the risk of death and worsening heart failure and improved symptoms across the broad spectrum of age studied in DAPA-HF. There was no significant imbalance in tolerability or safety events between dapagliflozin and placebo, even in elderly individuals. Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT03036124.
Maintenance Rituximab Improves Outcomes in Mantle Cell Lymphoma Patients Who Respond to Induction Therapy with Bendamustine + Rituximab without Autologous Transplant
Authors: Brian T. Hill, Jeffrey M. Switchenko, Peter Martin, Michael C. Churnetski, Yazeed Sawalha, Subir Goyal, Krithika Shanmugasundaram, Oscar Calzada, Bhaskar Kolla, Veronika Bachanova, James N. Gerson, Stefan K. Barta, Max J. Gordon, Alexey Danilov, Natalie S Grover, Stephanie Mathews, Madelyn Burkart, Reem Karmali, Nilanjan Ghosh, Steven I Park, Narendranath Epperla, David A. Bond, Talha Badar, Kristie A. Blum, Jin Guo, Mehdi Hamadani, Timothy S. Fenske, Mary-Kate Malecek, Brad S. Kahl, Christopher R. Flowers, Jonathon B. Cohen
Journal: Blood (2019)