tbuckley/cabot-search huggingface dataset:
When I use a word . . .: Re: re-
Authors: Jeff Aronson
Journal: BMJ (2001)

I have been asked why I used the word “reduplication” in a piece about dilatation (BMJ 2000;320:625), when “duplication” would have done just as well. Now it is true that the first definition of reduplication in the Oxford English Dictionary is “the action of doubling or folding,” which is just what duplication means. However, “reduplication” has a distinct grammatical meaning, not shared by “duplication”: “repetition of a syllable or letter, especially in the case of verbal forms.” Typically this occurs in the perfect tense of Greek and Latin verbs. For example, the paradigm of the Latin word to touch is tango, tangere, tetigi, tactum, with reduplication in the perfect tense, mimicking the repetition of a past action.

A reduplication is also “a word form produced by repetition of a syllable.” Examples include helter-skelter, gaga, hurdy-gurdy, tip-top. In some languages reduplication is simply used to indicate a plural, but there are other uses. For example, it can indicate intensity, as in beri-beri, which is probably from the Sinhalese word beri (debility)—that is, much debility. Or repetition, as in the onomatopoeic borborygmi (multiple rumbling of the guts). Or continuity, as in murmur and susurrus.

Japanese is rich in reduplications, and some medical examples have been imported into English. Itai-itai is painful osteomalacia secondary to cadmium induced nephropathy; it means ouch-ouch, an example of the onomatopoeic use of reduplication, as in ding-dong and bow-wow. Moya-moya disease, a cause of stroke in young people, is occlusion of the internal carotid arteries or of arteries in the circle of Willis, causing a collateral circulation, responsible for the typical angiographic pattern, which resembles a puff of smoke (moya-moya in Japanese); the term has also been used to describe fuzzy echoes seen during echocardiography.

Reduplicated words, such as those above, are also called reiterative words. Reiterate also seems to contain a redundant re-. To iterate means to repeat or go over again; to reiterate means to go over again and again. But the latter has displaced the former in general use.

Another word for all this reduplication, palillogy, comes from the Greek word παλι ′υ (palin), meaning back or again. But perhaps the best is frequentative (adjective and noun). Coming as it does from frequent, you might expect it to be frequentive, but the reduplication in the middle makes the point.
Association of NSAID Use and Renal Complications—Reply
Authors: Zachary Bouck, Noah M. Ivers, R. Sacha Bhatia
Journal: JAMA Internal Medicine (2019)

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Midbiotics: conjugative plasmids for genetic engineering of natural gut flora
Authors: Pilvi Ruotsalainen, Reetta Penttinen, Sari Mattila, Matti Jalasvuori
Journal: Gut Microbes (2019)

The possibility to modify gut bacterial flora has become an important goal, and various approaches are used to achieve desirable communities. However, the genetic engineering of existing microbes in the gut, which are already compatible with the rest of the community and host immune system, has not received much attention. Here, we discuss and experimentally evaluate the possibility to use modified and mobilizable CRISPR-Cas9-endocing plasmid as a tool to induce changes in bacterial communities. This plasmid system (briefly midbiotic) is delivered from bacterial vector into target bacteria via conjugation. Compared to, for example, bacteriophage-based applications, the benefits of conjugative plasmids include their independence of any particular receptor(s) on host bacteria and their relative immunity to bacterial defense mechanisms (such as restriction-modification systems) due to the synthesis of the complementary strand with host-specific epigenetic modifications. We show that conjugative plasmid in association with a mobilizable antibiotic resistance gene targeting CRISPR-plasmid efficiently causes ESBL-positive transconjugants to lose their resistance, and multiple gene types can be targeted simultaneously by introducing several CRISPR RNA encoding segments into the transferred plasmids. In the rare cases where the midbiotic plasmids failed to resensitize bacteria to antibiotics, the CRISPR spacer(s) and their adjacent repeats or larger regions were found to be lost. Results also revealed potential caveats in the design of conjugative engineering systems as well as workarounds to minimize these risks.
Prolonged lung cancer screening reduced 10-year mortality in the MILD trial: new confirmation of lung cancer screening efficacy
Authors: U. Pastorino, M. Silva, S. Sestini, F. Sabia, M. Boeri, A. Cantarutti, N. Sverzellati, G. Sozzi, G. Corrao, A. Marchianò
Journal: Annals of Oncology (2019)

The National Lung Screening Trial showed that lung cancer (LC) screening by three annual rounds of low-dose computed tomography (LDCT) reduces LC mortality. We evaluated the benefit of prolonged LDCT screening beyond 5 years, and its impact on overall and LC specific mortality at 10 years.
Direct-acting antivirals after successful treatment of early hepatocellular carcinoma improve survival in HCV-cirrhotic patients
Authors: Giuseppe Cabibbo, Ciro Celsa, Vincenza Calvaruso, Salvatore Petta, Irene Cacciola, Maria Rita Cannavò, Salvatore Madonia, Margherita Rossi, Bianca Magro, Francesca Rini, Marco Distefano, Licia Larocca, Tullio Prestileo, Giuseppe Malizia, Gaetano Bertino, Francesco Benanti, Anna Licata, Ignazio Scalisi, Giovanni Mazzola, Maria Antonietta Di Rosolini, Giuseppe Alaimo, Alfonso Averna, Fabio Cartabellotta, Nicola Alessi, Salvatore Guastella, Maurizio Russello, Gaetano Scifo, Giovanni Squadrito, Giovanni Raimondo, Franco Trevisani, Antonio Craxì, Vito Di Marco, Calogero Cammà
Journal: Journal of Hepatology (2019)
Treatment of Multiple Myeloma: ASCO and CCO Joint Clinical Practice Guideline
Authors: Joseph Mikhael, Nofisat Ismaila, Matthew C. Cheung, Caitlin Costello, Madhav V. Dhodapkar, Shaji Kumar, Martha Lacy, Brea Lipe, Richard F. Little, Anna Nikonova, James Omel, Namrata Peswani, Anca Prica, Noopur Raje, Rahul Seth, David H. Vesole, Irwin Walker, Alexander Whitley, Tanya M. Wildes, Sandy W. Wong, Tom Martin
Journal: Journal of Clinical Oncology (2019)

To provide evidence-based recommendations on the treatment of multiple myeloma to practicing physicians and others.ASCO and Cancer Care Ontario convened an Expert Panel of medical oncology, surgery, radiation oncology, and advocacy experts to conduct a literature search, which included systematic reviews, meta-analyses, randomized controlled trials, and some phase II studies published from 2005 through 2018. Outcomes of interest included survival, progression-free survival, response rate, and quality of life. Expert Panel members used available evidence and informal consensus to develop evidence-based guideline recommendations.The literature search identified 124 relevant studies to inform the evidence base for this guideline.Evidence-based recommendations were developed for patients with multiple myeloma who are transplantation eligible and those who are ineligible and for patients with relapsed or refractory disease.
Mobilization of CD8+ T Cells via CXCR4 Blockade Facilitates PD-1 Checkpoint Therapy in Human Pancreatic Cancer
Authors: Yongwoo David Seo, Xiuyun Jiang, Kevin M. Sullivan, Florencia G. Jalikis, Kimberly S. Smythe, Arezou Abbasi, Marissa Vignali, James O. Park, Sara K. Daniel, Seth M. Pollack, Teresa S. Kim, Raymond Yeung, Ian Nicholas Crispe, Robert H. Pierce, Harlan Robins, Venu G. Pillarisetty
Journal: Clinical Cancer Research (2019)

Pancreatic ductal adenocarcinoma (PDA) is rarely cured, and single-agent immune checkpoint inhibition has not demonstrated clinical benefit despite the presence of large numbers of CD8
Beneficial Effect of Adjuvant Dabrafenib Plus Trametinib on Recurrence-Free Survival in Patients With Resected <i>BRAF</i><sup>V600</sup>-Mutant Stage III Melanoma Seems to be Short-Lived
Authors: Kenneth R. Hess
Journal: Journal of Clinical Oncology (2019)

In their recent article in Journal of Clinical Oncology, Hauschild et al 1 reported relapse-free survival (RFS) results after extended follow-up in a randomized trial with adjuvant dabrafenib (D) plus trametinib (T) in patients with resected BRAF V600 -mutant stage III melanoma.They reported an overall hazard ratio estimate of 0.47 in favor of D plus T. Kaplan-Meier plots suggest that there is a sustained treatment effect because the 4-year RFS rates were 54% in the D plus T arm and 38% in the placebo arm.
Association of Indoor Tanning Exposure With Age at Melanoma Diagnosis and BRAF V600E Mutations
Authors: Toni E Burbidge, Boris C Bastian, Danny Guo, Haocheng Li, Don G Morris, Jose G Monzon, Gabriella Leung, Huiming Yang, Tina Cheng
Journal: JNCI Journal of the National Cancer Institute (2019)

There is limited information on how indoor tanning promotes melanoma development. We investigated indoor tanning use in patients with melanomas in sun-exposed skin and studied the clinicopathological and molecular characteristics in relation to indoor tanning exposure. Patients from a multidisciplinary clinic for cutaneous cancers completed standardized questionnaires on risk factors for melanoma as a component of medical history at their initial consultations. For this study, we included patients from December 2013 to May 2015. The 114 patients who reported indoor tanning exposure were younger at diagnosis than the 222 patients who did not (51.5 vs 64.0 years, two-sided P < .001). BRAF V600E genotype was more prevalent in ever-users than in nonusers (42.9% vs 28.3%, two-sided P = .04) and higher in ever-users who initiated indoor tanning prior to age 25 years compared with age 25 years or older (62.2% vs 31.1%, two-sided P = .003). There were more melanomas in intermittently sun-exposed skin in ever-users than nonusers (65.7% vs 51.9%, respectively, two-sided P = .02). Our data suggest indoor tanning may promote melanomas that arise in skin with low-chronic sun-induced damage through BRAF V600E-mediated melanomagenesis.
Chitinase-3-like-1 deficiency attenuates ethanol-induced liver injury by inhibition of sterol regulatory element binding protein 1-dependent triglyceride synthesis
Authors: Dong Hun Lee, Ji Hye Han, Yong Sun Lee, Young Suk Jung, Yoon Seok Roh, Jae Suk Yun, Sang Bae Han, Jin Tae Hong
Journal: Metabolism (2019)
Using fMRI connectivity to define a treatment-resistant form of post-traumatic stress disorder
Authors: Amit Etkin, Adi Maron-Katz, Wei Wu, Gregory A. Fonzo, Julia Huemer, Petra E. Vértes, Brian Patenaude, Jonas Richiardi, Madeleine S. Goodkind, Corey J. Keller, Jaime Ramos-Cejudo, Yevgeniya V. Zaiko, Kathy K. Peng, Emmanuel Shpigel, Parker Longwell, Russ T. Toll, Allison Thompson, Sanno Zack, Bryan Gonzalez, Raleigh Edelstein, Jingyun Chen, Irene Akingbade, Elizabeth Weiss, Roland Hart, Silas Mann, Kathleen Durkin, Steven H. Baete, Fernando E. Boada, Afia Genfi, Jillian Autea, Jennifer Newman, Desmond J. Oathes, Steven E. Lindley, Duna Abu-Amara, Bruce A. Arnow, Nicolas Crossley, Joachim Hallmayer, Silvia Fossati, Barbara O. Rothbaum, Charles R. Marmar, Edward T. Bullmore, Ruth O’Hara
Journal: Science Translational Medicine (2019)

A mechanistic understanding of the pathology of psychiatric disorders has been hampered by extensive heterogeneity in biology, symptoms, and behavior within diagnostic categories that are defined subjectively. We investigated whether leveraging individual differences in information-processing impairments in patients with post-traumatic stress disorder (PTSD) could reveal phenotypes within the disorder. We found that a subgroup of patients with PTSD from two independent cohorts displayed both aberrant functional connectivity within the ventral attention network (VAN) as revealed by functional magnetic resonance imaging (fMRI) neuroimaging and impaired verbal memory on a word list learning task. This combined phenotype was not associated with differences in symptoms or comorbidities, but nonetheless could be used to predict a poor response to psychotherapy, the best-validated treatment for PTSD. Using concurrent focal noninvasive transcranial magnetic stimulation and electroencephalography, we then identified alterations in neural signal flow in the VAN that were evoked by direct stimulation of that network. These alterations were associated with individual differences in functional fMRI connectivity within the VAN. Our findings define specific neurobiological mechanisms in a subgroup of patients with PTSD that could contribute to the poor response to psychotherapy.
Abstract 17535: Clinical and Echocardiographic Predictors of Mortality in Patients With Severe Aortic Stenosis and Left Ventricular Systolic Dysfunction
Authors: Jennifer A Rymer, Amit N Vora, Fawaz Alenezi, Allison Dunning, Eric Velazquez, Zainab Samad
Journal: Circulation (2017)

Introduction: Patients with severe aortic stenosis (AS) and consequent or concomitant left ventricular systolic dysfunction (LVSD) represent a high risk group. However, predictors of mortality in t...
Sham-Controlled Randomized Trials of Catheter-Based Renal Denervation in Patients With Hypertension
Authors: Partha Sardar, Deepak L. Bhatt, Ajay J. Kirtane, Kevin F. Kennedy, Saurav Chatterjee, Jay Giri, Peter A. Soukas, William B. White, Sahil A. Parikh, Herbert D. Aronow
Journal: Journal of the American College of Cardiology (2019)
Mitochondrial hypoxic stress induces widespread RNA editing by APOBEC3G in natural killer cells
Authors: Shraddha Sharma, Jianmin Wang, Emad Alqassim, Scott Portwood, Eduardo Cortes Gomez, Orla Maguire, Per H. Basse, Eunice S. Wang, Brahm H. Segal, Bora E. Baysal
Journal: Genome biology (2019)

Protein recoding by RNA editing is required for normal health and evolutionary adaptation. However, de novo induction of RNA editing in response to environmental factors is an uncommon phenomenon. While APOBEC3A edits many mRNAs in monocytes and macrophages in response to hypoxia and interferons, the physiological significance of such editing is unclear. Here, we show that the related cytidine deaminase, APOBEC3G, induces site-specific C-to-U RNA editing in natural killer cells, lymphoma cell lines, and, to a lesser extent, CD8-positive T cells upon cellular crowding and hypoxia. In contrast to expectations from its anti-HIV-1 function, the highest expression of APOBEC3G is shown to be in cytotoxic lymphocytes. RNA-seq analysis of natural killer cells subjected to cellular crowding and hypoxia reveals widespread C-to-U mRNA editing that is enriched for genes involved in mRNA translation and ribosome function. APOBEC3G promotes Warburg-like metabolic remodeling in HuT78 T cells under similar conditions. Hypoxia-induced RNA editing by APOBEC3G can be mimicked by the inhibition of mitochondrial respiration and occurs independently of HIF-1α. APOBEC3G is an endogenous RNA editing enzyme in primary natural killer cells and lymphoma cell lines. This RNA editing is induced by cellular crowding and mitochondrial respiratory inhibition to promote adaptation to hypoxic stress.
<i>MYH9</i>‐related disease mutations cause abnormal red blood cell morphology through increased myosin‐actin binding at the membrane
Authors: Alyson S. Smith, Kasturi Pal, Roberta B. Nowak, Anastasiya Demenko, Carlo Zaninetti, Lydie Da Costa, Remi Favier, Alessandro Pecci, Velia M. Fowler
Journal: American Journal of Hematology (2019)

MYH9-related disease (MYH9-RD) is a rare, autosomal dominant disorder caused by mutations in MYH9, the gene encoding the actin-activated motor protein non-muscle myosin IIA (NMIIA). MYH9-RD patients suffer from bleeding syndromes, progressive kidney disease, deafness, and/or cataracts, but the impact of MYH9 mutations on other NMIIA-expressing tissues remains unknown. In human red blood cells (RBCs), NMIIA assembles into bipolar filaments and binds to actin filaments (F-actin) in the spectrin-F-actin membrane skeleton to control RBC biconcave disk shape and deformability. Here, we tested the effects of MYH9 mutations in different NMIIA domains (motor, coiled-coil rod, or non-helical tail) on RBC NMIIA function. We found that MYH9-RD does not cause clinically significant anemia and that patient RBCs have normal osmotic deformability as well as normal membrane skeleton composition and micron-scale distribution. However, analysis of complete blood count data and peripheral blood smears revealed reduced hemoglobin content and elongated shapes, respectively, of MYH9-RD RBCs. Patients with mutations in the NMIIA motor domain had the highest numbers of elongated RBCs. Patients with mutations in the motor domain also had elevated association of NMIIA with F-actin at the RBC membrane. Our findings support a central role for motor domain activity in NMIIA regulation of RBC shape and define a new sub-clinical phenotype of MYH9-RD.
Abstract 12317: Sex Differences in Lipid Phenotypes Among Young Patients With Acute Myocardial Infarction
Authors: Yuan Lu, Rachel Dreyer, Peter Herbert, Michael Caulfield, Karthik Murugiah, Mary Geda, Elizabeth A Jackson, Judith Lichtman, Nancy Lorenze, Gail D'Onofrio, Erica Spatz, John Spertus, Harlan Krumholz
Journal: Circulation (2015)

Introduction: Young women (≤55 years) with acute myocardial infarction (AMI) have higher rates of mortality and morbidity than similarly aged men. An abnormal lipid profile following AMI is a risk factor for recurrent cardiovascular events and may contribute to worse outcomes in young women. However, little is known about the extent to which young women and men with AMI have similar or distinct lipid profiles after hospital discharge. We characterized sex difference in lipid phenotypes in young patients with AMI. Methods: We included 2,217 AMI patients (715 men and 1,502 women) aged 18-55 years from the VIRGO study. Standard lipid profile and lipoprotein subclasses were measured 1-month after discharge for AMI. Both sexes were compared on three dyslipidemia phenotypes: 1) increased low-density lipoprotein cholesterol (LDL-C≥100 mg/dL), 2) decreased high-density lipoprotein cholesterol (HDL-C&lt;40 mg/dL for men, &lt;50 mg/dL for women), and 3) increased small/medium LDL particles, decreased large HDL particles, and decreased LDL peak particle size (cutoffs based on sex-specific tertile values of healthy individuals). We also compared patient characteristics between sexes and used t-tests to assess statistical significance. Results: The median age was 48 years for both sexes. At baseline, women were more likely than men to be black, single, to have financial strain, obesity and diabetes (all P values&lt;0.001). At 1-month after hospital discharge, women had higher rates of dyslipidemia phenotypes than men, including increased LDL-C (P=0.031, see Table) and an atherogenic phenotype characterized by multiple lipoprotein subclasses (P&lt;0.001). The latter had the largest difference between men and women. The proportion of decreased HDL-C was similar for both sexes (P=0.300). Conclusion: Young women have higher rates of dyslipidemia phenotypes than men at 1-month after discharge for AMI. Effective interventions are needed to improve lipid control in young women with AMI.
Abstract 16075: Direct Comparison of Cardioprotective Effects of Different Necroptosis Inhibitors in the Rat Model of Global Ischemia-Reperfusion Injury
Authors: Yuri Dmitriev, Sarkis Minasian, Valentina Bayrasheva, Enena Demchenko, Michael Galagudza
Journal: Circulation (2017)

Background: The cardioprotective efficacy of necroptosis inhibitors (NI) has never been compared in a single study. We investigated the cardioprotective effects of four different NI in the isolated...
Irritability and Its Clinical Utility in Major Depressive Disorder: Prediction of Individual-Level Acute-Phase Outcomes Using Early Changes in Irritability and Depression Severity
Authors: Manish K. Jha, Abu Minhajuddin, Charles South, A. John Rush, Madhukar H. Trivedi
Journal: American Journal of Psychiatry (2019)

The authors evaluated improvement in irritability with antidepressant treatment and its prognostic utility in treatment-seeking adult outpatients with major depressive disorder.Mixed-model analyses were used to assess changes in irritability (as measured with the five-item irritability domain of the Concise Associated Symptom Tracking [CAST-IRR] scale) from baseline to week 4 after controlling for depression severity (as measured with the 16-item Quick Inventory of Depressive Symptomatology-Clinician Rated [QIDS-C]) in the Combining Medications to Enhance Depression Outcomes (CO-MED) trial (N=664). An interactive calculator for remission (QIDS-C score ≤5) and no meaningful benefit (<30% reduction in QIDS-C score from baseline) at week 8 was developed with logistic regression analyses in the CO-MED trial using participants with complete data (N=431) and independently replicated in the Suicide Assessment and Methodology Study (SAMS) (N=163).In the CO-MED trial, irritability was significantly reduced (effect size=1.06) from baseline to week 4, and this reduction remained significant after adjusting for QIDS-C change (adjusted effect size=0.36). A one-standard-deviation greater reduction in CAST-IRR score from baseline to week 4 predicted a 1.73 times higher likelihood of remission and a 0.72 times lower likelihood of no meaningful benefit at week 8, independent of baseline QIDS-C and CAST-IRR scores and reduction in QIDS-C score from baseline to week 4. The model estimates for remission (area under the curve [AUC]=0.79) and no meaningful benefit (AUC=0.76) in the CO-MED trial were used to predict remission (AUC=0.80) and no meaningful benefit (AUC=0.84) in SAMS and to develop an interactive calculator.Irritability is an important symptom domain of major depressive disorder that is not fully reflected in depressive symptom severity measures. Early reductions in irritability, when combined with changes in depressive symptom severity, provide a robust estimate of likelihood of remission or no meaningful benefit in outpatients with major depression.
Drugs could be exported for profit in a no deal Brexit, warn industry bosses
Authors: Lynn Eaton
Journal: BMJ (2019)

Pharmaceutical industry bosses fear that stockpiles of drugs held in the UK could be sold overseas in the event of a post-Brexit slump in the pound.

Unless the government steps in to ban such exports if there is a no deal Brexit, they warn that there will be huge profits to be made selling UK drug stocks elsewhere in Europe.

The risk would affect all drugs currently stored in the UK, not just those manufactured in the UK.

The Association of British Pharmaceutical Industries (ABPI) wants …