tbuckley/cabot-search huggingface dataset:
AV Nodal Wenckebach Masquerading as Infra-His Wenckebach Due to Intra-atrial Conduction Delay
Authors: Sandeep Bansal
Journal: JAMA Internal Medicine (2019)

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Therapeutic Targeting of Non-oncogene Dependencies in High-risk Neuroblastoma
Authors: Chen-Tsung Huang, Chiao-Hui Hsieh, Wen-Chi Lee, Yen-Lin Liu, Tsai-Shan Yang, Wen-Ming Hsu, Yen-Jen Oyang, Hsuan-Cheng Huang, Hsueh-Fen Juan
Journal: Clinical Cancer Research (2019)

Neuroblastoma is a pediatric malignancy of the sympathetic nervous system with diverse clinical behaviors. Genomic amplification of MYCN oncogene has been shown to drive neuroblastoma pathogenesis and correlate with aggressive disease, but the survival rates for those high-risk tumors carrying no MYCN amplification remain equally dismal. The paucity of mutations and molecular heterogeneity has hindered the development of targeted therapies for most advanced neuroblastomas. We use an alternative method to identify potential drugs that target nononcogene dependencies in high-risk neuroblastoma.By using a gene expression-based integrative approach, we identified prognostic signatures and potentially effective single agents and drug combinations for high-risk neuroblastoma.Among these predictions, we validated in vitro efficacies of some investigational and marketed drugs, of which niclosamide, an anthelmintic drug approved by the FDA, was further investigated in vivo. We also quantified the proteomic changes during niclosamide treatment to pinpoint nucleoside diphosphate kinase 3 (NME3) downregulation as a potential mechanism for its antitumor activity.Our results establish a gene expression-based strategy to interrogate cancer biology and inform drug discovery and repositioning for high-risk neuroblastoma.
Inherited non-alcoholic fatty liver disease and dyslipidemia due to monoallelic ABHD5 mutations
Authors: Leila Youssefian, Hassan Vahidnezhad, Amir Hossein Saeidian, Sara Pajouhanfar, Soheila Sotoudeh, Parvin Mansouri, Davoud Amirkashani, Sirous Zeinali, Michael A. Levine, Ketty Peris, Roberto Colombo, Jouni Uitto
Journal: Journal of Hepatology (2019)
Online multifactorial prevention programme has no effect on the number of running-related injuries: a randomised controlled trial
Authors: Tryntsje Fokkema, Robert-Jan de Vos, John M van Ochten, Jan A N Verhaar, Irene S Davis, Patrick J E Bindels, Sita M A Bierma-Zeinstra, Marienke van Middelkoop
Journal: British Journal of Sports Medicine (2019)

Objective To examine the effect of a multifactorial, online injury prevention programme on the number of running-related injuries (RRIs) in recreational runners. Methods Adult recreational runners who registered for a running event (distances 5 km up to 42.195 km) were randomised into the intervention group or control group. Participants in the intervention group were given access to the online injury prevention programme, which consisted of information on evidence-based risk factors and advices to reduce the injury risk. Participants in the control group followed their regular preparation for the running event. The primary outcome measure was the number of self-reported RRIs in the time frame between registration for a running event and 1 month after the running event. Results This trial included 2378 recreational runners (1252 men; mean [SD] age 41.2 [11.9] years), of which 1196 were allocated to the intervention group and 1182 to the control group. Of the participants in the intervention group 37.5% (95% CI 34.8 to 40.4) sustained a new RRI during follow-up, compared with 36.7% (95% CI 34.0 to 39.6) in the control group. Univariate logistic regression analysis showed no significant difference between the intervention and control group (OR 1.08; 95% CI 0.90 to 1.30). Furthermore, the prevention programme seemed to have a negative impact on the occurrence of new RRIs in the subgroup of runners with no injuries in the 12 months preceding the trial (OR 1.30; 95% CI 0.99 to 1.70). Conclusion A multifactorial, online injury prevention programme did not decrease the total number of RRIs in recreational runners. Trial registration number NTR5998.
Abstract 108: New Assessment Of Comprehensive Coagulation Function Using Clot Waveform Analysis In Patients With Kawasaki Disease In The Acute Phase
Authors: Hiroyuki Yoshizawa, Keiji Nogami, Tomoko Matsumoto, Tamaki Hayashi, Midori Shima
Journal: Circulation (2015)

Background: Hypercoagulability for Kawasaki disease (KD) in the acute phase is known, through many reports based on the change of the individual coagulation factor. Little information on the assessment of comprehensive coagulation function of this disease is described, however. A recent developed clot waveform analysis (CWA), defines changes in light transmittance that occur during the process of clot formation, can assess comprehensive coagulation function qualitatively and quantitatively by measuring the parameters. In this study, we have investigated the clotting dynamics of acute-phase KD by CWA. Method: The subjects were 43 patients of KD with treatment of intravenous γ-globulin (IVIG), at onset ranged from 3 months to 5 years old (median 1.8 years old). Normal pooled plasma (NP) was prepared from 20 healthy individuals. Blood samples were collected at three points of time; before the IVIG administration (Pre), after 1 week of IVIG (1W), and after 1 month of IVIG (1M). Cases with anticoagulant medication were excluded. CWA was performed using MDA-II™, and parameters, clotting time (CT), maximum coagulation velocity (dT/dt,
Psychiatrist is struck off for dishonestly reporting interview to employment tribunal
Authors: Clare Dyer
Journal: BMJ (2019)

A consultant psychiatrist has been struck off the UK medical register after a tribunal found that she dishonestly wrote a false expert witness report and gave untrue evidence at an employment tribunal.

Jane McLennan, who worked in old age psychiatry for NHS Lothian in Edinburgh, also had an extensive private practice preparing expert witness reports. These included reports for claimants and for employers at employment tribunals.

In 2014 she was instructed by the Ministry of Justice to interview its former employee, Mr A, who was claiming that he had been unfairly dismissed on the grounds of a disability—in his case, depression.

In an interview of nearly two hours she took just three pages of notes, and she then waited three weeks before completing her report. The report purported to quote Mr A extensively, …
Abstract 17889: MiR-92a Regulates Autophagy in a Cell Type Specific Manner
Authors: Wesley T Abplanalp, Eva-Maria Rogg, Angelika Bonauer, Ariane Fischer, Andreas M Zeiher, Stefanie Dimmeler
Journal: Circulation (2017)

MicroRNAs (miRs) have been shown to be novel regulators in nearly all biological pathways. Since dysregulation of miRs can lead to disease progression, they are being explored as novel therapeutic ...
Editor's Note: From the Cyclooxygenase-2 Inhibitor Celecoxib to a Novel Class of 3-Phosphoinositide-Dependent Protein Kinase-1 Inhibitors
Authors: Jiuxiang Zhu, Jui-Wen Huang, Ping-Hui Tseng, Ya-Ting Yang, Joseph Fowble, Chung-Wai Shiau, Yeng-Jeng Shaw, Samuel K. Kulp, Ching-Shih Chen
Journal: Cancer Research (2019)

The editors are publishing this note to alert the readers to a concern about [this article][1] ([1][2]). The editors were made aware of apparent splicing between Western blot lanes 3 and 4 in Fig. 7B. Ohio State University (Columbus, OH) conducted an investigation, but was not able to determine
Auranofin Protects Intestine against Radiation Injury by Modulating p53/p21 Pathway and Radiosensitizes Human Colon Tumor
Authors: Dhrubajyoti Nag, Payel Bhanja, Randal Riha, Giselle Sanchez-Guerrero, Bruce F. Kimler, Terance T. Tsue, Chris Lominska, Subhrajit Saha
Journal: Clinical Cancer Research (2019)

Abstract Purpose: The radiosensitivity of the normal intestinal epithelium is the major limiting factor for definitive radiotherapy against abdominal malignancies. Radiosensitizers, which can be used without augmenting radiation toxicity to normal tissue, are still an unmet need. Inhibition of proteosomal degradation is being developed as a major therapeutic strategy for anticancer therapy as cancer cells are more susceptible to proteasomal inhibition–induced cytotoxicity compared with normal cells. Auranofin, a gold-containing antirheumatoid drug, blocks proteosomal degradation by inhibiting deubiquitinase inhibitors. In this study, we have examined whether auranofin selectively radiosensitizes colon tumors without promoting radiation toxicity in normal intestine. Experimental Design: The effect of auranofin (10 mg/kg i.p.) on the radiation response of subcutaneous CT26 colon tumors and the normal gastrointestinal epithelium was determined using a mouse model of abdominal radiation. The effect of auranofin was also examined in a paired human colonic organoid system using malignant and nonmalignant tissues from the same patient. Results: Both in the mouse model of intestinal injury and in the human nonmalignant colon organoid culture, auranofin pretreatment prevented radiation toxicity and improved survival with the activation of p53/p21–mediated reversible cell-cycle arrest. However, in a mouse model of abdominal tumor and in human malignant colonic organoids, auranofin inhibited malignant tissue growth with inhibition of proteosomal degradation, induction of endoplasmic reticulum stress/unfolded protein response, and apoptosis. Conclusions: Our data suggest that auranofin is a potential candidate to be considered as a combination therapy with radiation to improve therapeutic efficacy against abdominal malignancies.
Safe and sustainable waste management of self care products
Authors: Ash Pachauri, Prerna Shah, Bethanie C Almroth, Norma P M Sevilla, Manjulaa Narasimhan
Journal: BMJ (2019)

Self Care InterventIonS for Sexual and reproduCtIve HealtHSafe and sustainable waste management of self care products A safe and sustainable waste management system for self care products requires education and multisectoral approaches say Ash Pachauri and colleagues• Safe and sustainable
68Ga-PSMA Uptake in Fibrous Dysplasia
Authors: Maria Lucia Reale, Consuelo Buttigliero, Marcello Tucci, Roberto Giardino, Carlo Poti
Journal: Clinical Nuclear Medicine (2019)

Abstract Prostate cancer is one of the most common malignancies. Imaging tools play an important role throughout the entire process of the disease. The scenario, however, is going to change. Thanks to a higher sensitivity and specificity, the use of the prostate-specific membrane antigen (PSMA) PET is of increasing importance, particularly at the time of diagnosis and in case of biochemical recurrence. Nevertheless, previous reports have described false-positive findings, as tracer-avid physiological findings or benign processes, potential pitfalls for interpretation of 68 Ga-PSMA PET/CT. Here we report a case of PSMA uptake in a histologically proven fibrous dysplasia.
Kdm6b regulates context-dependent hematopoietic stem cell self-renewal and leukemogenesis
Authors: Cates Mallaney, Elizabeth L. Ostrander, Hamza Celik, Ashley C. Kramer, Andrew Martens, Alok Kothari, Won Kyun Koh, Emily Haussler, Naoki Iwamori, Paul Gontarz, Bo Zhang, Grant A. Challen
Journal: Leukemia (2019)
Biallelic expansion of an intronic repeat in RFC1 is a common cause of late-onset ataxia
Authors: Andrea Cortese, Roberto Simone, Roisin Sullivan, Jana Vandrovcova, Huma Tariq, Wai Yan Yau, Jack Humphrey, Zane Jaunmuktane, Prasanth Sivakumar, James Polke, Muhammad Ilyas, Eloise Tribollet, Pedro J. Tomaselli, Grazia Devigili, Ilaria Callegari, Maurizio Versino, Vincenzo Salpietro, Stephanie Efthymiou, Diego Kaski, Nick W. Wood, Nadja S. Andrade, Elena Buglo, Adriana Rebelo, Alexander M. Rossor, Adolfo Bronstein, Pietro Fratta, Wilson J. Marques, Stephan Züchner, Mary M. Reilly, Henry Houlden
Journal: Nature Genetics (2019)
TREAT eDelphi exercise for AE photo‐ and systemic therapy registries
Authors: L.A.A. Gerbens, C.J. Apfelbacher, A.D. Irvine, S. Barbarot, R.J. de Booij, A.E. Boyce, M. Deleuran, L.F. Eichenfield, M.H. Hof, M.A. Middelkamp‐Hup, A. Roberts, J. Schmitt, C. Vestergaard, D. Wall, S. Weidinger, P.R. Williamson, C. Flohr, P.I. Spuls
Journal: British Journal of Dermatology (2019)

Atopic eczema (AE) is sometimes severe enough to need strong medicines, but there is not much information available to help doctors select the right treatment. Published trials of different drugs are difficult to assess because they include carefully selected patients and measure responses in different ways. Data from patients actually using these drugs outside of research trials, collected in a registry, could provide a much better picture of long‐term, real‐life experience, but only if everyone reports their observations in the same terms (“outcome measures”). In this study the international TREatment of ATopic eczema (TREAT) Registry Taskforce conducted an online exercise to agree a minimum set of variables that should be measured and reported to AE registries. An initial list of 119 possible items was sent to 479 participants in 36 countries: mostly doctors but also nurses, researchers, patients, industry and regulatory body representatives; 86% responded, rating each item from 0 (not important) to 9 (critical). The list was whittled down through two further rounds; after each round, a summary of the responses was fed back and participants were invited to either keep or change their original answers. Finally, 42 participants attended a consensus meeting and agreed a core set of 49 baseline items and 20 follow‐up items. Hopefully standardising outcome measures in future trials will fill the current gaps of evidence and improve the care of people with AE. However, as the accompanying editorial points out, agreeing outcome measures is only one of many challenges in developing effective registries.
Influence on mortality trendsof 'false positive' asthma death certification in elderly subjects
Authors: T. Aiken, D. Reid, V. Hendrick, W. T. Berrill, D. J. Hendrick
Journal: Thorax (1996)

Thirty five respiratory physicians, distributed in panels of 3, reviewed the hospital and general practice records of 210 subjects thought to have had asthma who died in 1991/2 in the Northern Health Region. Each acted independently and without sight of the death certificates. The certificates indicated that asthma had been certified as the direct cause of death in 103 (Group 1), as a contributory cause in 70 (Group 2), and as of no relevance in 37 (Group 3). Each panel reviewed a batch of 15 cases, knowing them to contain cases from each certification group. For 190 cases there were sufficient data for panels to express a majority or unanimous conclusion as to whether asthma was the direct cause of death, a contributory cause, or not relevant: Group 1 Group 2 Group 3 Panel Conclusion (n = 86) (n = 67) (n = 37) Direct 31 1 4 Contributory 13 5 4 Not Relevant 42 61 29 There was concordance between panels and certifying physicians that asthma was the direct cause of death in only 36% of the evaluable cases from Group 1, and was of no relevance to death in 78% of the evaluable cases from Group 3. The degree of discordance within Group 1 (ie 'false positives') was related to age at death, being 45% for those aged <65yr, but 75% for those who were older. If such discordance occurs nationally, the estimated number of 'false positive' certifications could account fully for the apparent increase in mortality evident from national statistics over recent decades. The error probably arises from increasing diagnostic transfer from other diseases, principally COPD. The 'false positive' certifications may, however, be counterbalanced overall by a failure to identify true asthma deaths (ie 'false negative' certifications).
Abstract 17876: NT Pro BNP After Surgery for Constrictive Pericarditis: Does It Increase or Decrease?
Authors: Swapnil S Lanjewar, Mazen Hanna, Leslie Cho, Allan Klein
Journal: Circulation (2014)

Background: It has been reported that patients with constrictive pericarditis (CP) have disproportionately lower BNP values compared to their clinical symptoms/signs of heart failure. This has been attributed to lesser stretching of the cardiac myocytes due to constriction. Hence, we hypothesized that surgical correction of constriction would cause an increase in ventricular volume and an elevation in NT pro BNP. Methods: We retrospectively reviewed charts of 221 patients who underwent surgery for CP. Patients were included if they had an NT pro BNP reported &lt;6 weeks before and between 6-52 weeks after surgery; and excluded if they had BNP before but NT pro BNP after surgery. The NYHA class during the encounter for NT pro BNP was noted to minimize selection bias based on symptoms. The NT pro BNP and its logarithm before and after surgery were compared using the Wilcoxon signed rank test. The left ventricular systolic, diastolic volumes and internal diameters on 2D ECHO were compared before and after surgery at dates closest to the NT pro BNP. Results: 17 patients with a median age of 61 [range 33-76, 5 males] met inclusion criteria. NT pro BNP was available a mean 146 days after surgery [range 43-351]. There was a significant increase in the NT pro BNP [mean 877.11 ± 191.1 pg/ml to 3332 ± 1249 pg/ml, p= 0.01] as well as log NT pro BNP [mean 2.715 ± 0.134 to 3.152 ± 0.146, p=0.004] after surgery. At the time of NT pro BNP evaluation post-surgery, the NYHA class was improved in 9, unchanged in 5 and worse in 3 patients. The left ventricular end diastolic volumes showed a trend towards increasing after surgery [103.08 ± 17.23 to 124.08 ± 16.28 ml, p=0.15]. Of the 17 patients, 12 before and 15 after surgery were on diuretics. Conclusions: The NT Pro BNP increases after surgery for CP. This is despite the fact that the NYHA class may remain stable or in fact improve after surgery. This increase in NT pro BNP can likely be explained by the increased cardiac volumes after surgery for CP. Thus post-surgery, an elevation in NT pro BNP can be expected without actual clinical deterioration. The use of diuretic therapy should still be guided by the NYHA class and symptoms. However, the increasing biomarker may reflect ongoing remodeling of the left ventricle after surgery.
A Novel Autocrine CXCL14/ACKR2 Axis: The Achilles' Heel of Cancer Metastasis?
Authors: Qian Zhang, Nianxin Zhou, Wei Wang, Shengtao Zhou
Journal: Clinical Cancer Research (2019)

Abstract Cancer-associated fibroblasts (CAF) are essential for cancer hallmarks. While CAFs are molecularly heterogeneous, a CXCL14-expressing subset has been a critical player in the cancer context. In breast cancer, an autocrine fibroblast CXCL14/ACKR2 axis mediates epithelial-to-mesenchymal transition and endows metastatic traits, which offers novel therapeutic potential in the clinical setting. See related article by Sjöberg et al., p. 3702
Emerging new roles of the lysosome and neuronal ceroid lipofuscinoses
Authors: Anil B. Mukherjee, Abhilash P. Appu, Tamal Sadhukhan, Sydney Casey, Avisek Mondal, Zhongjian Zhang, Maria B. Bagh
Journal: Molecular Neurodegeneration (2019)

Neuronal Ceroid Lipofuscinoses (NCLs), commonly known as Batten disease, constitute a group of the most prevalent neurodegenerative lysosomal storage disorders (LSDs). Mutations in at least 13 different genes (called CLNs) cause various forms of NCLs. Clinically, the NCLs manifest early impairment of vision, progressive decline in cognitive and motor functions, seizures and a shortened lifespan. At the cellular level, all NCLs show intracellular accumulation of autofluorescent material (called ceroid) and progressive neuron loss. Despite intense studies the normal physiological functions of each of the CLN genes remain poorly understood. Consequently, the development of mechanism-based therapeutic strategies remains challenging. Endolysosomal dysfunction contributes to pathogenesis of virtually all LSDs. Studies within the past decade have drastically changed the notion that the lysosomes are merely the terminal degradative organelles. The emerging new roles of the lysosome include its central role in nutrient-dependent signal transduction regulating metabolism and cellular proliferation or quiescence. In this review, we first provide a brief overview of the endolysosomal and autophagic pathways, lysosomal acidification and endosome-lysosome and autophagosome-lysosome fusions. We emphasize the importance of these processes as their dysregulation leads to pathogenesis of many LSDs including the NCLs. We also describe what is currently known about each of the 13 CLN genes and their products and how understanding the emerging new roles of the lysosome may clarify the underlying pathogenic mechanisms of the NCLs. Finally, we discuss the current and emerging therapeutic strategies for various NCLs.
Neurodevelopmental Outcomes after Intravitreal Bevacizumab Therapy for Retinopathy of Prematurity
Authors: Yuan-Yao Fan, Yu-Shu Huang, Chung-Ying Huang, Jen-Fu Hsu, Chia-Pang Shih, Yih-Shiou Hwang, Tsung-Chieh Yao, Chi-Chun Lai, Wei-Chi Wu
Journal: Ophthalmology (2019)
Gastric fundal splenosis presenting as a stromal tumor and diagnosed by endoscopic ultrasound-guided SharkCore biopsy
Authors: Ilenia Barbuscio, Alberto Fantin, Matteo Ghisa, Edoardo Vincenzo Savarino, Claudia Mescoli, Fabio Farinati
Journal: Endoscopy (2019)

The term splenosis refers to a rare condition, consisting of ectopic autotransplantation of splenic tissue into cavities of the human body or parenchymatous organs after splenic trauma or splenectomy [1]. The most frequent implantation sites include the greater omentum, the serosa of the small and large intestines, the parietal peritoneum, the mesentery, and the diaphragm. Less common sites are the liver, pancreas, stomach, bladder, gallbladder, kidney, ureter, and uterus [2]. It is usually asymptomatic, discovered incidentally during imaging or surgery. However, in some cases it has been associated with abdominal discomfort, gastrointestinal bleeding, abdominal pain, infarction of an intraperitoneal tissue nodule, and hydronephrosis due to ureteric compression [2]. Given the absence of potential malignancy, splenosis does not require follow-up or surgical treatment, except in patients who are symptomatic [3].
Examining the Treatment Patterns and Blood Counts Among Patients with Polycythemia Vera Treated with Hydroxyurea in the United States: An Analysis from the Reveal Study
Authors: Michael Richard Grunwald, Ivy Altomare, John M. Burke, Aaron T. Gerds, Mark A. Walshauser, Michael R. Savona, David J Kuter, Brady Lee Stein, Stephen Oh, Philomena Colucci, Ahmad B. Naim, Dilan Chamikara Paranagama, Ruben A Mesa
Journal: Blood (2017)