tbuckley/cabot-search huggingface dataset:
lncRNA SNHG11 Promotes Gastric Cancer Progression by Activating the Wnt/β-Catenin Pathway and Oncogenic Autophagy
Authors: Qiong Wu, Jiali Ma, Jue Wei, Wenying Meng, Yugang Wang, Min Shi
Journal: Molecular Therapy (2020)

Long non-coding RNAs (lncRNAs) are under active investigation in the development of cancers, including gastric cancer (GC). Oncogenic autophagy is required for cancer cell survival. The present study aimed to investigate the regulatory role of lncRNA small nucleolar host gene 11 (SNHG11) in GC. We show that SNHG11 is upregulated in GC, and that its upregulation correlated with dismal patient outcomes. Functionally, SNHG11 aggravated oncogenic autophagy to facilitate cell proliferation, stemness, migration, invasion, and epithelial-to-mesenchymal transition (EMT) in GC. Mechanistically, SNHG11 post-transcriptionally upregulated catenin beta 1 (CTNNB1) and autophagy related 12 (ATG12) through miR-483-3p/miR-1276, while the processing of precursor (pre-)miR-483/pre-miR-1276 was hindered by SNHG11. SNHG11 induced GSK-3β ubiquitination through interacting with Cullin 4A (CUL4A) to further activate the Wnt/β-catenin pathway. Intriguingly, SNHG11 regulated autophagy in a manner dependent on ATG12 rather than the Wnt/β-catenin pathway, whereas SNHG11 contributed to the malignant behaviors of GC cells via both pathways. Finally, SNHG11 upregulation in GC cells was shown to be transcriptionally induced by TCF7L2. In conclusion, we reveal that SNHG11 is an onco-lncRNA in GC and might be a promising prognostic and therapeutic target for GC. Long non-coding RNAs (lncRNAs) are under active investigation in the development of cancers, including gastric cancer (GC). Oncogenic autophagy is required for cancer cell survival. The present study aimed to investigate the regulatory role of lncRNA small nucleolar host gene 11 (SNHG11) in GC. We show that SNHG11 is upregulated in GC, and that its upregulation correlated with dismal patient outcomes. Functionally, SNHG11 aggravated oncogenic autophagy to facilitate cell proliferation, stemness, migration, invasion, and epithelial-to-mesenchymal transition (EMT) in GC. Mechanistically, SNHG11 post-transcriptionally upregulated catenin beta 1 (CTNNB1) and autophagy related 12 (ATG12) through miR-483-3p/miR-1276, while the processing of precursor (pre-)miR-483/pre-miR-1276 was hindered by SNHG11. SNHG11 induced GSK-3β ubiquitination through interacting with Cullin 4A (CUL4A) to further activate the Wnt/β-catenin pathway. Intriguingly, SNHG11 regulated autophagy in a manner dependent on ATG12 rather than the Wnt/β-catenin pathway, whereas SNHG11 contributed to the malignant behaviors of GC cells via both pathways. Finally, SNHG11 upregulation in GC cells was shown to be transcriptionally induced by TCF7L2. In conclusion, we reveal that SNHG11 is an onco-lncRNA in GC and might be a promising prognostic and therapeutic target for GC.
Longitudinal antibody and T cell responses in Ebola virus disease survivors and contacts: an observational cohort study
Authors: Ruth Thom, Thomas Tipton, Thomas Strecker, Yper Hall, Joseph Akoi Bore, Piet Maes, Fara Raymond Koundouno, Sarah Katharina Fehling, Verena Krähling, Kimberley Steeds, Anitha Varghese, Graham Bailey, Mary Matheson, Saidou Kouyate, Moussa Coné, Balla Moussa Keita, Sekou Kouyate, Amento Richard Ablam, Lies Laenen, Valentijn Vergote, Malcolm Guiver, Joseph Timothy, Barry Atkinson, Lisa Ottowell, Kevin S Richards, Andrew Bosworth, Stephanie Longet, Jack Mellors, Delphine Pannetier, Sophie Duraffour, César Muñoz-Fontela, Oumou Sow, Lamine Koivogui, Edmund Newman, Stephan Becker, Armand Sprecher, Herve Raoul, Julian Hiscox, Ana Maria Henao-Restrepo, Keita Sakoba, N'Faly Magassouba, Stephan Günther, Mandy Kader Konde, Miles W Carroll
Journal: The Lancet Infectious Diseases (2020)

The 2013-16 Ebola virus disease epidemic in west Africa caused international alarm due to its rapid and extensive spread resulting in a significant death toll and social unrest within the affected region. The large number of cases provided an opportunity to study the long-term kinetics of Zaire ebolavirus-specific immune response of survivors in addition to known contacts of those infected with the virus.
Re: Paolo Afonso de Carvalho, Joāo A.B.A. Barbosa, Giuliano B. Guglielmetti, et al. Retrograde Release of the Neurovascular Bundle with Preservation of Dorsal Venous Complex During Robot-assisted Radical Prostatectomy: Optimizing Functional Outcomes. Eur Urol 2020;77:628–35
Authors: Francesco Montorsi, Giorgio Gandaglia, Christoph Würnschimmel, Markus Graefen, Alberto Briganti, Hartwig Huland
Journal: European Urology (2020)
Stathmin-2: adding another piece to the puzzle of TDP-43 proteinopathies and neurodegeneration
Authors: Jonathan D. Glass
Journal: Journal of Clinical Investigation (2020)

Cytoplasmic aggregated proteins are a common neuropathological feature of neurodegenerative diseases. Cytoplasmic mislocalization and aggregation of TAR-DNA binding protein 43 (TDP-43) is found in the majority of patients with amyotrophic lateral sclerosis (ALS) and in approximately 50% of patients dying of frontotemporal lobar degeneration (FTLD). In this issue of the JCI, Prudencio, Humphrey, Pickles, and colleagues investigated the relationship of TDP-43 pathology with the loss of stathmin-2 (STMN2), an essential protein for axonal growth and maintenance. Comparing genetic, cellular, and neuropathological data from patients with TDP-43 proteinopathies (ALS, ALS–frontotemporal dementia [ALS-FTD], and FTLD-TDP-43 [FTLD-TDP]) with data from patients with non-TDP–related neurodegenerations, they demonstrate a direct relationship between TDP-43 pathology and STMN2 reduction. Loss of the normal transcription suppressor function of TDP-43 allowed transcription of an early termination cryptic axon, resulting in truncated, nonfunctional mRNA. The authors suggest that measurement of truncated STMN2 mRNA could be a biomarker for discerning TDP proteinopathies from other pathologies.
After the Night Shift
Authors: Phoebe Prioleau
Journal: Annals of Internal Medicine (2020)

Ad Libitum20 October 2020After the Night ShiftPhoebe Prioleau, MD, MPHPhoebe Prioleau, MD, MPHUniversity Hospitals Rainbow Babies & Children's Hospital, Cleveland, Ohio (P.P.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/M19-1177 Audio Reading - “After the Night Shift” Audio. Michael A. Lacombe, MD, Annals Associate Editor, reads “After the Night Shift” by Phoebe Prioleau, MD, MPH 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 I walk homemy stethoscope still heavyon my shoulderspast two geeseand a lone robinsinging to himself.Clouds flank the plumpand pockmarked moon.It smells somewhere between night and dawn. Author, Article, and Disclosure InformationAffiliations: University Hospitals Rainbow Babies & Children's Hospital, Cleveland, Ohio (P.P.)Current Author Address: Phoebe Prioleau, MD, MPH, 11100 Euclid Avenue, Cleveland, OH 44106. PreviousarticleNextarticle Advertisement Audio Reading - “After the Night Shift” Audio. Michael A. Lacombe, MD, Annals Associate Editor, reads “After the Night Shift” by Phoebe Prioleau, MD, MPH 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 20 October 2020Volume 173, Issue 8Page: 684KeywordsShouldersSmell ePublished: 20 October 2020 Issue Published: 20 October 2020 Copyright & PermissionsCopyright © 2020 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Complexities and Outcomes of Advance Care Planning
Authors: Joni Gilissen, Lieve Van den Block, Lara Pivodic
Journal: JAMA Internal Medicine (2020)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Internal Medicine journal
Clinical, FDG-PET and molecular markers of immune checkpoint inhibitor response in patients with metastatic Merkel cell carcinoma
Authors: Alison M Weppler, Andrew Pattison, Prachi Bhave, Paolo De Ieso, Jeanette Raleigh, Athena Hatzimihalis, Anthony J Gill, Shiva Balachander, Jason Callahan, Margaret Chua, George Au-Yeung, Grant A McArthur, Rodney J Hicks, Richard W Tothill, Shahneen Sandhu
Journal: Journal for ImmunoTherapy of Cancer (2020)

Background Metastatic Merkel cell carcinoma (mMCC) is an aggressive neuroendocrine malignancy of the skin with a poor prognosis. Immune checkpoint inhibitors (ICIs) have shown substantial efficacy and favorable safety in clinical trials. Methods Medical records of patients (pts) with mMCC treated with ICIs from August 2015 to December 2018 at Peter MacCallum Cancer Centre in Australia were analyzed. Response was assessed with serial imaging, the majority with FDG-PET/CT scans. RNA sequencing and immunohistochemistry for PD-L1, CD3 and Merkel cell polyomavirus (MCPyV) on tumor samples was performed. Results 23 pts with mMCC were treated with ICIs. A median of 8 cycles (range 1 to 47) were administered, with treatment ongoing in 6 pts. Objective responses (OR) were observed in 14 pts (61%): 10 (44%) complete responses (CR) and 4 (17%) partial responses (PR). Median time to response was 8 weeks (range 6 to 12) and 12-month progression-free survival rate was 39%. Increased OR were seen in pts aged less than 75 (OR 80% vs 46%), no prior history of chemotherapy (OR 64% vs 50%), patients with an immune-related adverse event (OR 100% vs 43%) and in MCPyV-negative tumors (OR 69% vs 43%). Pts with a CR had lower mean metabolic tumor volume on baseline FDG-PET/CT scan (CR: 35.7 mL, no CR: 187.8 mL, p=0.05). There was no correlation between PD-L1 positivity and MCPyV status (p=0.764) or OR (p=0.245). 10 pts received radiation therapy (RT) during ICI: 4 pts started RT concurrently (OR 75%, CR 50%), 3 pts had isolated ICI-resistant lesions successfully treated with RT and 3 pts with multisite progression continued to progress despite RT. Overall, 6 pts (26%) had grade 1–2 immune-related adverse events. Conclusion ICIs showed efficacy and safety in mMCC consistent with trial data. Clinical and imaging predictors of response were identified.
Care during covid-19: partner attendance at maternity services
Authors: Sebastian Walsh, Fiona Simmons-Jones, Rebecca Best
Journal: BMJ (2020)

Coulter and Richards highlight the concern held that hospital visitor restrictions have been applied in a blanket fashion that ignores the important role of some visitors, including “barred fathers from labour wards.”1 The most obvious concern is that partners will miss the birth of their own children, or at least be asked to leave shortly afterwards. Beyond this, however, women might receive devastating news at antenatal …
Epidemiological changes on the Isle of Wight after the launch of the NHS Test and Trace programme: a preliminary analysis
Authors: Michelle Kendall, Luke Milsom, Lucie Abeler-Dörner, Chris Wymant, Luca Ferretti, Mark Briers, Chris Holmes, David Bonsall, Johannes Abeler, Christophe Fraser
Journal: The Lancet Digital Health (2020)
51 Vitamin D deficiency shows no relationship to disease activity in an irish inflammatory bowel disease (IBD) population
Authors: FM Jones, O McCarthy, A Lavelle, P Twomey, H Mulcahy, G Cullen, J Sheridan, GA Doherty
Journal: Gut (2017)

Background  Low levels of vitamin D have been widely reported in IBD with evidence suggesting a role in disease severity and treatment.  Aim  Ireland has high rates of vitamin D deficiency both in IBD and general populations. Studies investigating correlation of vitamin D deficiency and disease parameters have been mixed.  Method  We conducted a single centre retrospective study in our hospital from Jan 2015- June 2016. The aim was to assess the prevalence of vitamin D deficiency in IBD and non-IBD cohorts and to assess the impact of vitamin D deficiency on disease activity in IBD. Patients were separated into 4 groups: Crohns Disease (CD), Ulcerative Colitis (UC), general gastroenterology (GI) and general medical (non-GI). Basic demographic data disease specific information was recorded. Vitamin D deficiency was defined as   Results  395 patients were studied: 157 CD, 70 UC, 75 GI and 93 non-GI. IBD patients were found to have high rates of Vitamin D deficiency (33% levels  Conclusions  We found very high rates of vitamin D deficiency in both IBD and non-IBD patients. Absolute levels did not differ significantly between groups. This may be accounted for by high overall prevalence of Vitamin D deficiency in this population or by confounders in the control population.
The “tax on wax”: why are GPs conniving with this reduction in basic NHS services?
Authors: Ted Leverton
Journal: BMJ (2020)

Helen Salisbury describes the way GPs have contributed to cutting the essential service of ear wax removal.1

An important cause of temporary deafness, ear wax also affects orientation, balance, and safety. It disproportionately affects the elderly, particularly those wearing aids, but also workers such as bus drivers, pilots, and construction workers.

GPs have always treated ear wax. Since electric irrigators became routine in the 1980s, treatment …
Equivalence Randomized Trial to Compare Treatment on the Basis of Sentinel Node Biopsy Versus Neck Node Dissection in Operable T1-T2N0 Oral and Oropharyngeal Cancer
Authors: Renaud Garrel, Gilles Poissonnet, Antoine Moyà Plana, Nicolas Fakhry, Gilles Dolivet, Benjamin Lallemant, Jérôme Sarini, Sebastien Vergez, Bruno Guelfucci, Olivier Choussy, Vianney Bastit, Fanny Richard, Valérie Costes, Paul Landais, Françoise Perriard, Jean Pierre Daures, Delphine de Verbizier, Valentin Favier, Marie de Boutray
Journal: Journal of Clinical Oncology (2020)

Sentinel node (SN) biopsy is accurate in operable oral and oropharyngeal cT1-T2N0 cancer (OC), but, to our knowledge, the oncologic equivalence of SN biopsy and neck lymph node dissection (ND; standard treatment) has never been evaluated.In this phase III multicenter trial, 307 patients with OC were randomly assigned to (1) the ND arm or (2) the SN arm (experimental arm: biopsy alone if negative, or followed by ND if positive, during primary tumor surgery). The primary outcome was neck node recurrence-free survival (RFS) at 2 years. Secondary outcomes were 5-year neck node RFS, 2- and 5-year disease-specific survival (DSS), and overall survival (OS). Other outcomes were hospital stay length, neck and shoulder morbidity, and number of physiotherapy prescriptions during the 2 years after surgery.Data on 279 patients (139 ND and 140 SN) could be analyzed. Neck node RFS was 89.6% (95% CI, 0.83% to 0.94%) at 2 years in the ND arm and 90.7% (95% CI, 0.84% to 0.95%) in the SN arm, confirming the equivalence with P < .01. The 5-year RFS and the 2- and 5-year DSS and OS were not significantly different between arms. The median hospital stay length was 8 days in the ND arm and 7 days in the SN arm (P < .01). The functional outcomes were significantly worse in the ND arm until 6 months after surgery.This study demonstrated the oncologic equivalence of the SN and ND approaches, with lower morbidity in the SN arm during the first 6 months after surgery, thus establishing SN as the standard of care in OC.
TPA-induced mitochondria-dependent generation of reactive oxygen species (ROS) in undifferentiated leukemic cells
Authors: Kassim Traore, Michael A. Trush
Journal: Cancer Research (2005)

4775  Increasing evidence indicates that transient generation of intracellular ROS may play a role in intracellular signaling. Recently, we reported that TPA induces generation of a required reactive oxygen species (ROS) signal for growth arrest during human myeloid leukemic cell differentiation via p21WAF1/cip1induction. In the present study, we sought to determine the source of this ROS in leukemic cell lines in response to TPA. Using luminol-dependent chemiluminescence(CL), we observed that TPA induced ROS generation in human ML-1 and THP-1 cells within 3 minutes of incubation. The generation of ROS was completely blocked by diphenyleneiodium (DPI), a commonly used inhibitor of both NADH and NADPH dependent enzymes. Western blotting analysis indicated the absence of key components, phox p47 and phox p67, of NADPH oxidase, in undifferentiated ML-1 cells pointing to mitochondria as the likely source of ROS in these cells. The mitochondrial complex I inhibitor rhein inhibited the TPA-induced CL. Microarray analysis and western blot analysis indicated the upregulation of mitochondria SOD2 expression within three hours of TPA treatment, suggestive of oxidative perturbation within mitochondria as an early response to TPA. Furthermore, our data indicate that TPA-induced SOD2 expression required not only generation of mitochondria dependent ROS, but also activation of the mitogen activated kinase cascade. We conclude that TPA -induced generation of optimal ROS from mitochondria complex I in undifferentiated ML-1 cells is required to initiate the signaling cascade involved in the inhibition of growth preceeding the mononuclear cell differentiation process.
THU0429 THE ASSOCIATION OF SERUM VITAMIN A, VITAMIN E, AND FOLATE WITH HYPERURICEMIA: AN ANALYSIS OF POPULATION-BASED NATIONALLY REPRESENTATIVE DATA
Authors: Y. Kim, G. T. Kim, J. Kang
Journal: Annals of the Rheumatic Diseases (2020)

Background: Hyperuricemia is an important risk factor for gout as well as hypertension, type 2 diabetes and renal impairment. Although previous studies investigated the association of questionnaire-based micronutrient intake with serum uric acid levels, limited data on serum micronutrients levels in relation to the risk of hyperuricemia especially in Asian population. Objectives: This study aimed to evaluate the association of serum vitamin A, vitamin E and folate level with hyperuricemia in the Korean general population. Methods: The present study included 6023 participants (2722 men and 3301 women) aged ≥19 years with available data on serum vitamin A, vitamin E, folate and serum uric acid. General characteristics of participants were compared using the Chi-square test and Student’s t test. The association between serum vitamin A, E and folate and serum uric acid levels were evaluated using general linear regression model. Multivariate logistic regression analyses were performed to estimate the effects of these micronutrients on hyperuricemia. Results: Serum uric acid levels were increased from the lowest quintile of vitamin A levels to the highest quintile after adjustment for covariates (P trend &lt; 0.001 in both sexes). In addition, dose-dependent relationship was observed between vitamin A levels and the risk of hyperuricemia in fully-adjusted analyses (P trend &lt; 0.001 in both sexes). However, neither serum vitamin E nor serum folate was associated with hyperuricemia across analyses models. Conclusion: This study suggested that vitamin A could be a risk factor of hyperuricemia and further studies are warranted to elucidate underlying mechanism of the observed findings. References: [1]Choi, Woo-Joo, et al. “Independent association of serum retinol and β-carotene levels with hyperuricemia: A national population study.” Arthritis care &amp; research 64.3 (2012): 389-396. Disclosure of Interests: : None declared
In adults with severe acute GI bleeding, tranexamic acid did not reduce death due to bleeding at 5 days
Authors: Laura C. Horton, Joseph D. Feuerstein
Journal: Annals of Internal Medicine (2020)

Source Citation The HALT-IT Trial Collaborators. Effects of a high-dose 24-h infusion of tranexamic acid on death and thromboembolic events in patients with acute gastrointestinal bleeding (HALT-IT): an international randomised, double-blind, placebo-controlled trial. Lancet. 2020;395:1927-36. 32563378
Tumor-targeted nanoparticles improve the therapeutic index of BCL2 and MCL1 dual inhibition
Authors: Neeta Bala Tannan, Mandana T. Manzari, Laurie Herviou, Mariana Da Silva Ferreira, Connor Hagen, Hiroto Kiguchi, Katia Manova-Todorova, Venkatraman Seshan, Elisa de Stanchina, Daniel A. Heller, Anas Younes
Journal: Blood (2020)
Angiogenesis after acute myocardial infarction
Authors: Xuekun Wu, Marc R Reboll, Mortimer Korf-Klingebiel, Kai C Wollert
Journal: Cardiovascular Research (2020)

Abstract Acute myocardial infarction (MI) inflicts massive injury to the coronary microcirculation leading to vascular disintegration and capillary rarefication in the infarct region. Tissue repair after MI involves a robust angiogenic response that commences in the infarct border zone and extends into the necrotic infarct core. Technological advances in several areas have provided novel mechanistic understanding of postinfarction angiogenesis and how it may be targeted to improve heart function after MI. Cell lineage tracing studies indicate that new capillary structures arise by sprouting angiogenesis from pre-existing endothelial cells (ECs) in the infarct border zone with no meaningful contribution from non-EC sources. Single-cell RNA sequencing shows that ECs in infarcted hearts may be grouped into clusters with distinct gene expression signatures, likely reflecting functionally distinct cell populations. EC-specific multicolour lineage tracing reveals that EC subsets clonally expand after MI. Expanding EC clones may arise from tissue-resident ECs with stem cell characteristics that have been identified in multiple organs including the heart. Tissue repair after MI involves interactions among multiple cell types which occur, to a large extent, through secreted proteins and their cognate receptors. While we are only beginning to understand the full complexity of this intercellular communication, macrophage and fibroblast populations have emerged as major drivers of the angiogenic response after MI. Animal data support the view that the endogenous angiogenic response after MI can be boosted to reduce scarring and adverse left ventricular remodelling. The improved mechanistic understanding of infarct angiogenesis therefore creates multiple therapeutic opportunities. During preclinical development, all proangiogenic strategies should be tested in animal models that replicate both cardiovascular risk factor(s) and the pharmacotherapy typically prescribed to patients with acute MI. Considering that the majority of patients nowadays do well after MI, clinical translation will require careful selection of patients in need of proangiogenic therapies.