tbuckley/cabot-search huggingface dataset:
Long non-coding RNA UCA1 promotes malignant phenotypes of renal cancer cells by modulating the miR-182-5p/DLL4 axis as a ceRNA
Authors: Wei Wang, Wentao Hu, Ya Wang, Yong An, Lei Song, Panfeng Shang, Zhongjin Yue
Journal: Molecular Cancer (2020)

Accumulating literatures have indicated that long non-coding RNAs (lncRNAs) are potential biomarkers that play key roles in tumor development and progression. Urothelial cancer associated 1 (UCA1) is a novel lncRNA that acts as a potential biomarker and is involved in the development of cancers. However, the molecular mechanism of UCA1 in renal cancer is still needed to further explore.The relative expression level of UCA1 was determined by Real-Time qPCR in a total of 88 patients with urothelial renal cancer and in different renal cancer cell lines. Loss-of-function experiments were performed to investigate the biological roles of UCA1 and miR-182-5p on renal cancer cell proliferation, migration, apoptosis and tumorigenicity. Comprehensive transcriptional analysis, dual-luciferase reporter assay and western blot etc. were performed to explore the molecular mechanisms underlying the functions of UCA1.In this study, we found that UCA1 was significantly up-regulated in renal cancer. Moreover, increased UCA1 expression was positively correlated with differentiation and advanced TNM stage. Further experiments demonstrated that knockdown of UCA1 inhibited malignant phenotypes and Notch signal path of renal cancer cells, and miR-182-5p was reverse function as UCA1. UCA1 functioned as a miRNA sponge to positively regulate the expression of Delta-like ligand 4(DLL4) through sponging miR-182-5p and subsequently promoted malignant phenotypes of renal cancer cells, thus UCA1 playing an oncogenic role and miR-182-5p as an antioncogenic one in renal cancer pathogenesis.UCA1-miR-182-5p-DLL4 axis is involved in proliferation and progression of renal cancer. Thus, this study demonstrated that UCA1 plays a critical regulatory role in renal cancer cell and UCA1 may serve as a potential diagnostic biomarker and therapeutic target of renal cancer.
Single-agent activity of phosphatidylinositol 3-kinase inhibition with copanlisib in patients with molecularly defined relapsed or refractory diffuse large B-cell lymphoma
Authors: Georg Lenz, Eliza Hawkes, Gregor Verhoef, Corinne Haioun, Soon Thye Lim, Dae Seog Heo, Kirit Ardeshna, Geoffrey Chong, Jacob Haaber, Wei Shi, Igor Gorbatchevsky, Susanne Lippert, Florian Hiemeyer, Paolo Piraino, Georg Beckmann, Carol Peña, Viktoriya Buvaylo, Barrett H. Childs, Gilles Salles
Journal: Leukemia (2020)

Abstract Patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) have adverse outcomes. We evaluated the efficacy and safety of the phosphatidylinositol 3-kinase inhibitor copanlisib in patients with relapsed/refractory DLBCL and assessed the relationship between efficacy and DLBCL cell of origin (COO; activated B-cell like [ABC] and germinal center B-cell like [GCB]) and other biomarkers. The primary endpoint was objective response rate (ORR) in DLBCL COO subgroups (ABC, GCB, and unclassifiable) and by CD79B mutational status (NCT02391116). Sixty-seven patients received copanlisib (ABC DLBCL, n = 19; GCB DLBCL, n = 30; unclassifiable, n = 3; missing, n = 15). The ORR was 19.4%; 31.6% and 13.3% in ABC and GCB DLBCL patients, respectively. ORR was 22.2%/20.0% for patients with/without CD79B mutations (wild type, n = 45; mutant, n = 9; missing, n = 13). Overall median progression-free survival and duration of response were 1.8 and 4.3 months, respectively. Adverse events included hypertension (40.3%), diarrhea (37.3%), and hyperglycemia (32.8%). Aberrations were detected in 338 genes, including BCL2 (53.7%) and MLL2 (53.7%). A 16-gene signature separating responders from nonresponders was identified. Copanlisib treatment demonstrated a manageable safety profile in patients with relapsed/refractory DLBCL and a numerically higher response rate in ABC vs. GCB DLBCL patients.
Offline: How to defeat political populism
Authors: Richard Horton
Journal: The Lancet (2020)

Here is US President Donald Trump last week in his State of the Union Address: "A good life for American families also requires the most affordable, innovative, and high-quality healthcare system on Earth...Over 130 legislators in this chamber have endorsed legislation that would bankrupt our nation by providing free taxpayer-funded healthcare to millions of illegal aliens, forcing taxpayers to subsidise free care for anyone in the world who unlawfully crosses our borders...If forcing American taxpayers to provide unlimited free healthcare to illegal aliens sounds fair to you, then stand with the radical left.
Abstract 9805: Chronic Beta3-Adrenergic Receptor Blockade Restores Beta-Adrenergic Positive Modulation on Cardiomyocyte L-Type Ca2+ Current in Rats With Advanced Heart Failure
Authors: Che Ping Cheng, Peng Zhou, Atsushi Morimoto, Xiaowei Zhang, David Zhao, David Herrington, Dalane Kitzman, Heng-Jie Cheng
Journal: Circulation (2019)

Background: β-adrenergic receptor (AR) stimulation modulating cardiac L-type Ca2+ current (ICa,L) plays an important role in the positive inotropic response to β-AR stimulation, and it has been sho...
LY6K promotes glioblastoma tumorigenicity via CAV-1–mediated ERK1/2 signaling enhancement
Authors: Namratha G Sastry, Xuechao Wan, Tianzhi Huang, Angel A Alvarez, Rajendra P Pangeni, Xiao Song, Charles David James, Craig M Horbinski, Cameron W Brennan, Ichiro Nakano, Bo Hu, Shi-Yuan Cheng
Journal: Neuro-Oncology (2020)

Lymphocyte antigen 6 complex, locus K (LY6K) is a putative oncogene in various cancers. Elevated expression of LY6K is correlated with poor patient prognosis in glioblastoma (GBM). The aim of this study is to advance our understanding of the mechanism by which LY6K contributes to GBM tumor biology.
Medical algorithms: Diagnosis and investigation of perioperative immediate hypersensitivity reactions
Authors: Lene H. Garvey, Birgitte Bech Melchiors, Didier G. Ebo, Paul‐Michel Mertes, Mogens Krøigaard
Journal: Allergy (2020)

None of the authors report conflict of interest related to the present work. LHG is an adjudication member for Novo Nordisk, Denmark and MSD, New Jersey US, outside the present work. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Targeted alpha therapy in a systemic mouse model of prostate cancer - a feasibility study
Authors: Andreea D Stuparu, Catherine A L Meyer, Susan L Evans-Axelsson, Katharina Lückerath, Liu H Wei, Woosuk Kim, Soumya Poddar, Christine E Mona, Magnus Dahlbom, Mark D Girgis, Caius G Radu, Johannes Czernin, Roger Slavik
Journal: Theranostics (2020)

Ac-PSMA-617 targeted-therapy has demonstrated efficacy in 75-85% of patients; however, responses are not durable. We aimed to establish translatable mouse models of disseminated prostate cancer (PCa) to evaluate effectiveness of
68Ga-PSMA PET/CT in Recurrence Prostate Cancer. Should We Perform Delayed Image in Cases of Negative 60 Minutes Postinjection Examination?
Authors: Jolanta Kunikowska, Szymon Kujda, Leszek Królicki
Journal: Clinical Nuclear Medicine (2020)

Abstract We report a case of a 59-year-old man with prostate adenocarcinoma, Gleason score 9 after prostatectomy and adjuvant radiotherapy. The patient showed biochemical recurrence. On standard 68 Ga-PSMA PET/CT examination, 60 minutes postinjection, the PET/CT images showed only trace accumulation in the ureters. To identify lesions close to the ureters, imaging of the pelvis was performed 2 hours postinjection. The delayed image showed clearly visible increased uptake in a right internal iliac lymph node that was normal-sized by CT. The patient underwent radiotherapy with planning based on the 68 Ga-PSMA PET/CT image. Follow-up testing showed prostate-specific antigen level reduction to 0.04 ng/mL.
Gabapentinoids: when hope is restored, it’s obvious that increasing analgesics will bring no benefit
Authors: David McGavin, Ingrid Hermansen
Journal: BMJ (2020)

Ian Hamilton need not be so downcast about alternatives for reducing gabapentinoid use.1

Kairos Rehabilitation, a registered charity, is a pain management clinic led by a GP with specialist interest, commissioned by Circle MSK for Greenwich Clinical Commissioning Group. We have furnished Hamilton’s call for “more support” with gentle therapies, …
Transforming the health system for the UK’s multiethnic population
Authors: Sarah Salway, Daniel Holman, Caroline Lee, Victoria McGowan, Yoav Ben-Shlomo, Sonia Saxena, James Nazroo
Journal: BMJ (2020)

Ethnic diversity is a global phenomenon resulting from historical and contemporary movements of people.However, healthcare policy makers, practitioners, and researchers have been slow to wake up to this reality.We urgently need to improve our understanding of, and responses to, the health needs of mobile and ethnically diverse populations.
101P Significant Antitumor Activity in A Randomized Phase 2 Study Comparing 2 Schedules of Nktr-102 In Patients (Pts) with Metastatic Breast Cancer (Mbc)
Authors: A. Awada, S. Chan, G.H.M. Jerusalem, R.E. Coleman, M.T. Huizing, A. Mehdi, S.M. O'Reilly, J.T. Hamm, A. Garcia, E. Perez
Journal: Annals of Oncology (2012)
A Rare Case of Primary Pleura Myxoid Leiomyosarcoma
Authors: Ling Wang, Yixuan Ren, Xiaofang Ding, Chi Dong, Jiangyan Liu
Journal: Clinical Nuclear Medicine (2020)

Abstract Myxoid leiomyosarcoma is a malignant tumor that originates from the mesenchymal tissue with extensive mucoid degeneration. It usually occurs in the uterus; occurrences from other tissues are extremely rare. Here we report the FDG PET/CT findings and clinicopathological of primary pleura myxoid leiomyosarcoma in a 51-year-old man.
Supportive roles of brain macrophages in CNS metastases and assessment of new approaches targeting their functions
Authors: Hua You, Szymon Baluszek, Bozena Kaminska
Journal: Theranostics (2020)

Metastases to the central nervous system (CNS) occur frequently in adults and their frequency increases with the prolonged survival of cancer patients. Patients with CNS metastases have short survival, and modern therapeutics, while effective for extra-cranial cancers, do not reduce metastatic burden. Tumor cells attract and reprogram stromal cells, including tumor-associated macrophages that support cancer growth by promoting tissue remodeling, invasion, immunosuppression and metastasis. Specific roles of brain resident and infiltrating macrophages in creating a pre-metastatic niche for CNS invading cancer cells are less known. There are populations of CNS resident innate immune cells such as: parenchymal microglia and non-parenchymal, CNS border-associated macrophages that colonize CNS in early development and sustain its homeostasis. In this study we summarize available data on potential roles of different brain macrophages in most common brain metastases. We hypothesize that metastatic cancer cells exploit CNS macrophages and their cytoprotective mechanisms to create a pre-metastatic niche and facilitate metastatic growth. We assess current pharmacological strategies to manipulate functions of brain macrophages and hypothesize on their potential use in a therapy of CNS metastases. We conclude that the current data strongly support a notion that microglia, as well as non-parenchymal macrophages and peripheral infiltrating macrophages, are involved in multiple stages of CNS metastases. Understanding their contribution will lead to development of new therapeutic strategies.
A key role for IL-13 signaling via the type 2 IL-4 receptor in experimental atopic dermatitis
Authors: Almog Bitton, Shmuel Avlas, Hadar Reichman, Michal Itan, Danielle Karo-Atar, Nurit P. Azouz, Perri Rozenberg, Yael Diesendruck, Limor Nahary, Marc E. Rothenberg, Itai Benhar, Ariel Munitz
Journal: Science Immunology (2020)

The type 2 IL-4 receptor has a key role in atopic dermatitis and is therefore a potential therapeutic target.
FGF9 induces functional differentiation to Schwann cells from human adipose derived stem cells
Authors: Chia-Wei Huang, Shih-Yu Lu, Tzu-Chieh Huang, Bu-Miim Huang, H. Sunny Sun, Shang-Hsun Yang, Jih-Ing Chuang, Yuan-Yu Hsueh, Yi-Ting Wu, Chia-Ching Wu
Journal: Theranostics (2020)

Rationale:The formation of adipose-derived stem cells (ASCs) into spheres on a chitosan-coated microenvironment promoted ASCs differentiation into a mixed population of neural lineage-like cells (NLCs), but the underline mechanism is still unknown.Since the fibroblast growth factor 9 (FGF9) and fibroblast growth factor receptors (FGFRs) play as key regulators of neural cell fate during embryo development and stem cell differentiation, the current study aims to reveal the interplay of FGF9 and FGFRs for promoting peripheral nerve regeneration.Methods: Different concentration of FGF9 peptide (10, 25, 50, 100 ng/mL) were added during NLCs induction (FGF9-NLCs).The FGFR expressions and potential signaling were studied by gene and protein expressions as well as knocking down by specific FGFR siRNA or commercial inhibitors.FGF9-NLCs were fluorescent labeled and applied into a nerve conduit upon the injured sciatic nerves of experimental rats.Results: The FGFR2 and FGFR4 were significantly increased during NLCs induction.The FGF9 treated FGF9-NLCs spheres became smaller and changed into Schwann cells (SCs) which expressed S100β and GFAP.The specific silencing of FGFR2 diminished FGF9-induced Akt phosphorylation and inhibited the differentiation of SCs.Transplanted FGF9-NLCs participated in myelin sheath formation, enhanced axonal regrowth and promoted innervated muscle regeneration.The knockdown of FGFR2 in FGF9-NLCs led to the abolishment of nerve regeneration.Conclusions: Our data therefore demonstrate the importance of FGF9 in the determination of SC fate via the FGF9-FGFR2-Akt pathway and reveal the therapeutic benefit of FGF9-NLCs.
Open Letter to a Burned-Out Intern
Authors: Sonia Singh
Journal: Annals of Internal Medicine (2020)

On Being a Doctor18 February 2020Open Letter to a Burned-Out InternSonia Singh, MDSonia Singh, MDMemorial Hermann Medical Group, Houston, Texas (S.S.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/M19-2668 Audio Reading - “Open Letter to a Burned-Out Intern” Audio. Michael A. Lacombe, MD, Annals Associate Editor, reads “Open Letter to a Burned-Out Intern” by Sonia Singh, MD Your browser does not support the audio element. Audio player progress bar Step backward in current audio track Play current audio trackPause current audio track Step forward in current audio track Mute current audio trackUnmute current audio track 00:00/ SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Dear Doctor,I'm writing this letter to you to say the things I wish someone had said to me 5 years ago. I will not pretend to understand everything you are going through—nobody can—but I suspect we have enough in common that at least parts of this letter will ring true and, more important, bring you comfort.I commend you for making it this far—for picking up this journal or clicking on this link in whatever stolen moment you have managed to do so. Perhaps you are reading this sitting among your colleagues as your attention strays from grand rounds ... Author, Article, and Disclosure InformationAffiliations: Memorial Hermann Medical Group, Houston, Texas (S.S.)Corresponding Author: Sonia Singh, MD, 6400 Fannin Street, Suite 2015, Houston, TX 77030; e-mail, sonia.[email protected]org. PreviousarticleNextarticle Advertisement Audio Reading - “Open Letter to a Burned-Out Intern” Audio. Michael A. Lacombe, MD, Annals Associate Editor, reads “Open Letter to a Burned-Out Intern” by Sonia Singh, MD Your browser does not support the audio element. Audio player progress bar Step backward in current audio track Play current audio trackPause current audio track Step forward in current audio track Mute current audio trackUnmute current audio track 00:00/ FiguresReferencesRelatedDetails Metrics 18 February 2020Volume 172, Issue 4Page: 289-290KeywordsBody fluidsEmotionsGlobal healthHeartHipResidencySleepSurgeons ePublished: 18 February 2020 Issue Published: 18 February 2020 Copyright & PermissionsCopyright © 2020 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Correlation of TCR diversity with immune reconstitution after cord blood transplant.
Authors: Ryan Emerson, Filippo Milano, Katherine Guthrie, Anna Sherwood, Colleen Delaney, Harlan Robins
Journal: Journal of Clinical Oncology (2012)

6631 Background: Umbilical cord blood is an important source of hematopoietic stem cells for allogeneic transplants used to treat hematologic disorders and malignancies. Stem cells from cord blood has several advantages over other sources (peripheral blood or marrow) including reduced incidence of graft-versus-host disease (GvHD) which allows less strict donor-patient HLA-type matching requirements. However, hematopoietic recovery (both myeloid and platelet engraftment) and immune reconstitution is significantly delayed in CBT patients resulting in patients remaining at high risk of infection for an extended period of time. Though the high risk of infections to patients is well-documented and recognized, physicians lack an objective means to monitor each patient’s progress toward functional reconstitution of the adaptive immune system. Our project aims to test if our measure of TCR diversity is a better proxy of immune reconstitution in CBT patients. Methods: To do this, we compare our proposed measure of immune reconstitution, TCRB CDR3 sequence diversity and richness over time, against the observed clinical course of severe infection in patients who have received CBT. Previously, peripheral blood mononuclear cells (PBMC) were collected and cyropreserved from 35 CBT recipients at six time points, pre-transplant, and 28, 56, 100, 180, and 365 days post-transplant. Concordantly, clinical outcomes for these patients were collected for up to four years post-transplant. We use a t-test to test if size of TCR repertoire differs between CBT patients with non-relapse related mortality and all other CBT patients. Results: Our TCR sequencing method was successful at measuring immune reconstitution, and TCR diversity is predictive of subsequent mortality from severe infection by 56 days post-transplant. Conclusions: TCR repertoire sequencing is a viable method to monitor immune reconstitution.
Associations between life-course-persistent antisocial behaviour and brain structure in a population-representative longitudinal birth cohort
Authors: Christina O Carlisi, Terrie E Moffitt, Annchen R Knodt, Honalee Harrington, David Ireland, Tracy R Melzer, Richie Poulton, Sandhya Ramrakha, Avshalom Caspi, Ahmad R Hariri, Essi Viding
Journal: The Lancet Psychiatry (2020)

Studies with behavioural and neuropsychological tests have supported the developmental taxonomy theory of antisocial behaviour, which specifies abnormal brain development as a fundamental aspect of life-course-persistent antisocial behaviour, but no study has characterised features of brain structure associated with life-course-persistent versus adolescence-limited trajectories, as defined by prospective data. We aimed to determine whether life-course-persistent antisocial behaviour is associated with neurocognitive abnormalities by testing the hypothesis that it is also associated with brain structure abnormalities.
PF783 TREG DOWNREGULATION IS ASSOCIATED WITH INCREASE OF T CELL RESPONSES AGAINST IMMUNOGENIC ANTIGENS AND CLINICAL RESPONSES IN PATIENTS WITH HEMATOLOGICAL MALIGNANCIES AFTER DONOR LYMPHOCYTE INFUSION
Authors: J. Greiner, M. Götz, M. Schmitt, M. Wiesneth, D. Bunjes, S. Hofmann
Journal: HemaSphere (2019)

Background: Cytotoxic T‐cell responses against malignant cells play a pivotal role in maintaining remission and prolonging overall‐survival after allogeneic stem cell transplantation (allo‐SCT) and donor lymphocyte infusion (DLI), however they are not well characterized so far. Aims: In this study, we focused on the detection of immune responses in patients before and after DLI. A broader epitope‐specific T cell activity is associated with clinical response of patients treated with DLI and additionally reduced regulatory T cell frequency may contribute to clinical response in patients after DLI. Methods: For a better characterization of the T cell responses, frequency and diversity of leukemia‐associated antigen (LAA)‐specific cytotoxic T cells was assessed using ELISpot and pMHC multimer assays. Furthermore, the frequency of regulatory T cells (Treg) before and after DLI was analyzed. Results were correlated to the clinical course of the patients. Results: Independently of their clinical response, over the course of DLI 7/11 patients (63.6%) showed an immunological response through an increase in the number of recognized epitopes. Comparing early screening and maximum response after DLI there was a significant increase (p = 0.02) in epitope recognition. A significant increase in the mean augmentation from 1 to 4 of the spotted epitopes in the course of DLI was detected in the cohort of clinical responders (R) compared to non‐responders (NR) who did not show any dynamics in epitope recognition with a median of 3 to 4 recognized LAA. The proportion of the CD4+CD25 high FoxP3+ Treg within the CD4+CD25 high T cell fraction decreased significantly in R from a median of 72.9% to 54.6% when comparing the variation at the time points before and after DLI (p = 0.04). In NR there was no significant change in the Treg fraction in the course of DLI. In general, significantly more LAA‐derived T cell epitopes (p = 0.02) were recognized in R when compared to NR. Moreover, the frequency of Treg in R decreased significantly (p = 0.008) while remaining stable in NR. Summary/Conclusion: Taken together, an increase of specific CTL responses against several LAA after DLI was detected. This study suggests that decreasing numbers of Treg as well as enhanced LAA diversity in T cell responses contribute to clinical outcome of patients treated with DLI.
Dietary Guidance From the International Organization for the Study of Inflammatory Bowel Diseases
Authors: Arie Levine, Jonathan M. Rhodes, James O. Lindsay, Maria T. Abreu, Michael A. Kamm, Peter R. Gibson, Christoph Gasche, Mark S. Silverberg, Uma Mahadevan, Rotem Sigall Boneh, Eyton Wine, Oriana M. Damas, Graeme Syme, Gina L. Trakman, Chu Kion Yao, Stefanie Stockhamer, Muhammad B. Hammami, Luis C. Garces, Gerhard Rogler, Ioannis E. Koutroubakis, Ashwin N. Ananthakrishnan, Liam McKeever, James D. Lewis
Journal: Clinical Gastroenterology and Hepatology (2020)