tbuckley/cabot-search huggingface dataset:
Case 37-2003: A 79-Year-Old Man with Coronary Artery Disease, Peripheral Vascular Disease, End-Stage Renal Disease, and Abdominal Pain and Distention
Authors: Michèle Barry
Journal: New England Journal of Medicine (2004)

Correction from The New England Journal of Medicine — Case 37-2003: A 79-Year-Old Man with Coronary Artery Disease, Peripheral Vascular Disease, End-Stage Renal Disease, and Abdominal Pain and Distention
Dupilumab Improves Asthma Control, and Allergic Rhinitis-Related Health-Related Quality of Life in Children With Uncontrolled Persistent Asthma With Comorbid Allergic Rhinitis
Authors: Alessandro Fiocchi, Wanda Phipatanakul, Sandy Durrani, Jeremy Cole, Dongfang Liu, Jérôme Msihid, David Lederer, Megan Hardin, Yi Zhang, Asif Khan
Journal: Journal of Allergy and Clinical Immunology (2022)

Children with asthma frequently have comorbid allergic rhinitis (AR). Dupilumab, a fully human monoclonal antibody, blocks the shared receptor component for interleukin (IL)-4/13, key and central drivers of type 2 (T2) inflammation in multiple diseases. VOYAGE, a 52-week, randomized, double-blind, placebo-controlled, phase 3 study (NCT02948959), evaluated dupilumab efficacy and safety in children aged 6–11 years with uncontrolled persistent asthma. We assessed the impact of dupilumab on asthma control (interviewer-administered 7-Item Asthma Control Questionnaire [ACQ-7-IA]) and AR-related health-related quality of life (HRQoL) (interviewer-administered Pediatric Rhinoconjunctivitis Quality of Life Questionnaire [PRQLQ-IA]) in children with a T2 inflammatory asthma phenotype (baseline blood eosinophils ≥150 cells/μL or FeNO ≥20 ppb), and co-existing AR. Children were treated with dupilumab (100/200 mg by body weight at randomization) or matched placebo every 2 weeks. We assessed changes from baseline in total ACQ-7-IA scores and PRQLQ-IA global and domain (Activity limitation, Eye symptoms, Nose symptoms, Practical problems, Other symptoms) scores ranging from 0−6 (lower scores indicating better QoL) in patients with coexisting AR. In VOYAGE, 84.6% of children had patient-reported comorbid AR history. At baseline, the majority (99.6%) of children had global PRQLQ-IA scores >0, showing they had impacted AR-related HRQoL. By Week 52, dupilumab significantly improved total ACQ-7-IA scores (least squares (LS) mean difference (LSMD) vs placebo [95% CI]: -0.50 [-0.66, -0.34]; P<0.0001), and PRQLQ-IA global (LSMD [95% CI]: -0.47 [-0.73, -0.20]; P<0.001), and all domain scores (P<0.05). Dupilumab improved asthma control and AR-related HRQoL in children with uncontrolled persistent T2 asthma with co-existing AR.
Within-Trial Cost-Effectiveness of Lifestyle Intervention or Metformin for the Primary Prevention of Type 2 Diabetes
Journal: Diabetes Care (2003)

OBJECTIVE—The Diabetes Prevention Program (DPP) demonstrated that intensive lifestyle and metformin interventions reduced the incidence of type 2 diabetes compared with a placebo intervention. The aim of this study was to assess the cost-effectiveness of the lifestyle and metformin interventions relative to the placebo intervention. RESEARCH DESIGN AND METHODS—Analyses were performed from a health system perspective that considered direct medical costs only and a societal perspective that considered direct medical costs, direct nonmedical costs, and indirect costs. Analyses were performed with the interventions as implemented in the DPP and as they might be implemented in clinical practice. RESULTS—The lifestyle and metformin interventions required more resources than the placebo intervention from a health system perspective, and over 3 years they cost approximately $2,250 more per participant. As implemented in the DPP and from a societal perspective, the lifestyle and metformin interventions cost $24,400 and $34,500, respectively, per case of diabetes delayed or prevented and $51,600 and $99,200 per quality-adjusted life-year (QALY) gained. As the interventions might be implemented in routine clinical practice and from a societal perspective, the lifestyle and metformin interventions cost $13,200 and $14,300, respectively, per case of diabetes delayed or prevented and $27,100 and $35,000 per QALY gained. From a health system perspective, costs per case of diabetes delayed or prevented and costs per QALY gained tended to be lower. CONCLUSIONS—Over 3 years, the lifestyle and metformin interventions were effective and were cost-effective from the perspective of a health system and society. Both interventions are likely to be affordable in routine clinical practice, especially if implemented in a group format and with generic medication pricing.
Multiplexed CRISPR-based microfluidic platform for clinical testing of respiratory viruses and identification of SARS-CoV-2 variants
Authors: Nicole L. Welch, Meilin Zhu, Catherine Hua, Juliane Weller, Marzieh Ezzaty Mirhashemi, Tien G. Nguyen, Sreekar Mantena, Matthew R. Bauer, Bennett M. Shaw, Cheri M. Ackerman, Sri Gowtham Thakku, Megan W. Tse, Jared Kehe, Marie-Martine Uwera, Jacqueline S. Eversley, Derek A. Bielwaski, Graham McGrath, Joseph Braidt, Jeremy Johnson, Felecia Cerrato, Gage K. Moreno, Lydia A. Krasilnikova, Brittany A. Petros, Gabrielle L. Gionet, Ewa King, Richard C. Huard, Samantha K. Jalbert, Michael L. Cleary, Nicholas A. Fitzgerald, Stacey B. Gabriel, Glen R. Gallagher, Sandra C. Smole, Lawrence C. Madoff, Catherine M. Brown, Matthew W. Keller, Malania M. Wilson, Marie K. Kirby, John R. Barnes, Daniel J. Park, Katherine J. Siddle, Christian T. Happi, Deborah T. Hung, Michael Springer, Bronwyn L. MacInnis, Jacob E. Lemieux, Eric Rosenberg, John A. Branda, Paul C. Blainey, Pardis C. Sabeti, Cameron Myhrvold
Journal: Nature Medicine (2022)

The coronavirus disease 2019 (COVID-19) pandemic has demonstrated a clear need for high-throughput, multiplexed and sensitive assays for detecting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and other respiratory viruses and their emerging variants. Here, we present a cost-effective virus and variant detection platform, called microfluidic Combinatorial Arrayed Reactions for Multiplexed Evaluation of Nucleic acids (mCARMEN), which combines CRISPR-based diagnostics and microfluidics with a streamlined workflow for clinical use. We developed the mCARMEN respiratory virus panel to test for up to 21 viruses, including SARS-CoV-2, other coronaviruses and both influenza strains, and demonstrated its diagnostic-grade performance on 525 patient specimens in an academic setting and 166 specimens in a clinical setting. We further developed an mCARMEN panel to enable the identification of 6 SARS-CoV-2 variant lineages, including Delta and Omicron, and evaluated it on 2,088 patient specimens with near-perfect concordance to sequencing-based variant classification. Lastly, we implemented a combined Cas13 and Cas12 approach that enables quantitative measurement of SARS-CoV-2 and influenza A viral copies in samples. The mCARMEN platform enables high-throughput surveillance of multiple viruses and variants simultaneously, enabling rapid detection of SARS-CoV-2 variants.
Table of Contents
Authors: Robert Schrier, Tomas Berl, Stuart Linas, Erika D'agata, Ibironke Apata, Stephanie Booth, John Boyce, Karen Deaver, Nicole Gualandi, Alicia Neu, Duc Nguyen, Sharon Novosad, Paul Palevsky, Darlene Rodgers, Andrew Beenken, Qais Al-Awqati, Raymond Geherty, Matthew Sparks, Laetitia Dou, Stéphane Burtey, Tilman Drüeke, Jürgen Floege, Ikechi Okpechi, Vivekanand Jha, Thomas Jacob, Sophie Dupuis, David Harris, Ruifeng Wang, Yiping Wang, Qi Cao, Francesco Schena, Vito Anelli, Joseph Trotta, Tommaso Noia, Carlo Manno, Giovanni Tripepi, Graziella Arrigo, Nicholas Chesnaye, Maria Russo, Maria Stangou, Aikaterini Papagianni, Carmine Zoccali, Vladimir Tesar
Journal: Kidney International (2021)
<scp>Aptamer‐Based</scp> Screen of Neuropsychiatric Lupus Cerebrospinal Fluid Reveals Potential Biomarkers That Overlap With the Choroid Plexus Transcriptome
Authors: Kamala Vanarsa, Prashanth Sasidharan, Valeria Duran, Sirisha Gokaraju, Malavika Nidhi, Anto Sam Crosslee Louis Sam Titus, Sanam Soomro, Ariel D. Stock, Evan Der, Chaim Putterman, Benjamin Greenberg, Chi Chiu Mok, John G. Hanly, Chandra Mohan
Journal: Arthritis & Rheumatology (2022)

As no gold-standard diagnostic test exists for neuropsychiatric systemic lupus erythematosus (NPSLE), we undertook this study to execute a broad screen of NPSLE cerebrospinal fluid (CSF) using an aptamer-based platform.CSF was obtained from NPSLE patients and subjected to proteomic assay using the aptamer-based screen. Potential biomarkers were identified and validated in independent NPSLE cohorts in comparison to other neurologic diseases.Forty proteins out of the 1,129 screened were found to be elevated in NPSLE CSF. Based on enzyme-linked immunosorbent assay validation, CSF levels of angiostatin, α2-macroglobulin, DAN, fibronectin, hepatocellular carcinoma clone 1, IgM, lipocalin 2, macrophage colony-stimulating factor (M-CSF), and serine protease inhibitor G1 were significantly elevated in a predominantly White NPSLE cohort (n = 24), compared to patients with other neurologic diseases (n = 54), with CSF IgM (area under the curve [AUC] 0.95) and M-CSF (AUC 0.91) being the most discriminatory proteins. In a second Hong Kong-based NPSLE cohort, CSF IgM (AUC 0.78) and lipocalin 2 (AUC 0.85) were the most discriminatory proteins. Several CSF proteins exhibited high diagnostic specificity for NPSLE in both cohorts. Elevated CSF complement C3 was associated with an acute confusional state. Eleven molecules elevated in NPSLE CSF exhibited concordant elevation in the choroid plexus, suggesting shared origins.Lipocalin 2, M-CSF, IgM, and complement C3 emerge as promising CSF biomarkers of NPSLE with diagnostic potential.
MKSAP X
Authors: HERBERT S. KING
Journal: Annals of Internal Medicine (1977)

Letters and Corrections1 October 1977MKSAP XHERBERT S. KING, M.D.HERBERT S. KING, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-87-4-496_3 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: After late-night study of the syllabus for the Medical Self-Assessment Program IV, I fantasized that I was off in the future and had received the following letter.1 November 2000Dear Doctor:Thank you for your subscription to the tenth edition of The American College of Physician's Medical Knowledge Self-Assessment Program.You may remember that the controversy as to whether the expansion of MKSAP III's 100 pages to the 300 of MKSAP IV heralded a linear or logarithmic growth came to a climax with the 900 pages of MKSAP V in 1980. It was then that the...References1. News section. Journal of the United Unrepentent Unrecertifieds, 1:37, 1980 Google Scholar2. ILLICH I: Medical Nemesis: The Expropriation of Health. New York, Pantheon Books, 1976 Google Scholar3. Archives of the Society for Outrageous Puns, 10:95, 1980 Google Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Staten Island Medical Group 307 Victory Boulevard Staten Island, NY 10301 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 October 1977Volume 87, Issue 4Page: 496-497KeywordsForecasting ePublished: 1 December 2008 Issue Published: 1 October 1977 PDF downloadLoading ...
WHO's new End TB Strategy
Authors: Mukund Uplekar, Diana Weil, Knut Lonnroth, Ernesto Jaramillo, Christian Lienhardt, Hannah Monica Dias, Dennis Falzon, Katherine Floyd, Giuliano Gargioni, Haileyesus Getahun, Christopher Gilpin, Philippe Glaziou, Malgorzata Grzemska, Fuad Mirzayev, Hiroki Nakatani, Mario Raviglione
Journal: The Lancet (2015)
Belfast—a personal journey
Authors: Martin McKee
Journal: BMJ (2022)

We went to the cinema last week.Hardly something to write about.But this was different.It was the first time since the start of the pandemic.And it was different in another way too.Usually we go for entertainment, to be amused, informed, or thrilled.This time it was a personal journey, to see a film that took me back to the city of my birth.That film was, of course, Belfast. 1 Written and directed by Kenneth Branagh, another Belfast boy who later moved to England, this semi-autobiographical film is shot in black and white.It conveys the grim reality he experienced as a child in 1969, growing up
Characterization of the “Frequent Exacerbator Phenotype” in Bronchiectasis
Authors: James D. Chalmers, Stefano Aliberti, Anna Filonenko, Michal Shteinberg, Pieter C. Goeminne, Adam T. Hill, Thomas C. Fardon, Dusanka Obradovic, Christoph Gerlinger, Giovanni Sotgiu, Elisabeth Operschall, Robert M. Rutherford, Katerina Dimakou, Eva Polverino, Anthony De Soyza, Melissa J. McDonnell
Journal: American Journal of Respiratory and Critical Care Medicine (2018)

Rationale: Exacerbations are key events in the natural history of bronchiectasis, but clinical predictors and outcomes of patients with frequently exacerbating disease are not well described.Objectives: To establish if there is a “frequent exacerbator phenotype” in bronchiectasis and the impact of exacerbations on long-term clinical outcomes.Methods: We studied patients with bronchiectasis enrolled from 10 clinical centers in Europe and Israel, with up to 5 years of follow-up. Patients were categorized by baseline exacerbation frequency (zero, one, two, or three or more per year). The repeatability of exacerbation status was assessed, as well as the independent impact of exacerbation history on hospitalizations, quality of life, and mortality.Measurements and Main Results: A total of 2,572 patients were included. Frequent exacerbations were the strongest predictor of future exacerbation frequency, suggesting a consistent phenotype. The incident rate ratios for future exacerbations were 1.73 (95% confidence interval [CI], 1.47–2.02; P < 0.0001) for one exacerbation per year, 3.14 (95% CI, 2.70–3.66; P < 0.0001) for two exacerbations, and 5.97 (95% CI, 5.27–6.78; P < 0.0001) for patients with three or more exacerbations per year at baseline. Additional independent predictors of future exacerbation frequency were Haemophilus influenzae and Pseudomonas aeruginosa infection, FEV1, radiological severity of disease, and coexisting chronic obstructive pulmonary disease. Patients with frequently exacerbating disease had worse quality of life and were more likely to be hospitalized during follow-up. Mortality over up to 5 years of follow-up increased with increasing exacerbation frequency.Conclusions: The frequent exacerbator phenotype in bronchiectasis is consistent over time and shows high disease severity, poor quality of life, and increased mortality during follow-up.
Dermatitis herpetiformis
Authors: G. Berg, C.A.M. Rietmeyer, Th.van Joost
Journal: British Journal of Dermatology (1990)

A 46-year-old man suddenly developed a generalized bullous dermatosis which was diagnosed elsewhere as dermatitis herpetiformis and treated with dapsone and a gluten-and iodine-free diet.Gastroduodenoscopy at that time revealed normal features and histological examination of a duodenal biopsy specimen showed no specific changes.After a good initial response to the therapy exacerbations occurred.The lower legs and feet were very tender, but the patient never suffered from pruritus.
Polarization of tumor-associated macrophages by TLR7/8 conjugated radiosensitive peptide hydrogel for overcoming tumor radioresistance
Authors: Yumin Zhang, Zujian Feng, Jinjian Liu, Hui Li, Qi Su, Jiamin Zhang, Pingsheng Huang, Weiwei Wang, Jianfeng Liu
Journal: Bioactive Materials (2022)
Large-scale neural recordings with single neuron resolution using Neuropixels probes in human cortex
Authors: Angelique C. Paulk, Yoav Kfir, Arjun R. Khanna, Martina L. Mustroph, Eric M. Trautmann, Dan J. Soper, Sergey D. Stavisky, Marleen Welkenhuysen, Barundeb Dutta, Krishna V. Shenoy, Leigh R. Hochberg, R. Mark Richardson, Ziv M. Williams, Sydney S. Cash
Journal: Nature Neuroscience (2022)
Die neueren chemotherapeutischen Präparate aus der Chininreihe (Optochin, im besonderen Eukupin und Vuzin) und aus der Akridinreihe (Trypaflavin Rivanol). Eine kritische Besprechung des bisherigen Erfolges und der Grundlagen der Therapie.
Journal: JAMA (1923)

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Covid-19: unravelling the conundrum of omicron and deaths
Authors: Gareth Iacobucci
Journal: BMJ (2022)

Covid-19: unravelling the conundrum of omicron and deathsCovid deaths in the UK are at their highest since February 2021 despite omicron being less severe than previous variants.Gareth Iacobucci investigates why Gareth IacobucciConfidence is growing among experts and ministers in the UK that omicron is milder than previous variants of SARS-CoV-2, and politicians and scientists alike are increasingly bullish that the worst of the covid-19 pandemic is behind us. 1 2 At the same time, the number of people dying from covid in the UK is higher than it has been since February 2021.
Instructions to Authors
Journal: Circulation Research (1974)

Circulation Research accepts for publication manuscripts that present the results of significant research on the cardiovascular and the renal systems.First priority is given to unpublished research that provides better understanding of mechanisms that influence normal or abnormal cardiovascular-renal function.The research may be in the field of biology, biochemistry, biophysics, clinical medicine, genetics, immunology, morphology, pathology, pharmacology, physiology, or theoretic biology-or it may be interdisciplinary.Lower priority is given to reports that merely confirm published work, that present a new method or a modification of an existing method without applying it to a biologic problem, or that are preliminary or incomplete.Since the number of papers that can be published each year is limited, only manuscripts that receive a relatively high priority can be accepted for publication.One complete long manuscript is preferred to several fragmented, interdependent manuscripts.
P117: THE INTERNATIONAL HAEMOGLOBINOPATHY RESEARCH NETWORK (INHERENT): AN INTERNATIONAL INITIATIVE TO STUDY THE ROLE OF GENETIC MODIFIERS IN HAEMOGLOBINOPATHIES
Authors: P Kountouris, C Stephanou, N Archer, F Bonifazi, V Giannuzzi, K Kuo, A Maggio, J Makani, M Mañú Pereira, K Michailidou, S Nkya, O Nnodu, S Trompeter, L Tshilolo, A Wonkam, B Zilfalil, B Inusa, M Kleanthous
Journal: HemaSphere (2022)

Background: Haemoglobinopathies, including sickle cell disease (SCD) and thalassaemia syndromes, represent the commonest monogenic diseases in the world. Although their pathogenicity is well established, the diverse clinical manifestations and the varying degree of severity are less understood and are thought to be governed, in part, by genetic modifiers. Despite the identification and characterisation of a few genetic modifiers by previous studies, these are as yet insufficient to guide treatment recommendations or stratify patients reliably. Larger, multi-ethnic studies are needed to identify and validate further disease modifiers that can be used for patient stratification and personalised treatment. There is a growing need for deeper insight with the availability of novel targeted therapies and potentially curative options like gene therapy in both SCD and thalaessemia. Aims: The International Haemoglobinopathy Research Network (INHERENT) is a recently established network with the aim of investigating the role of genetic modifiers in haemoglobinopathies, through a large-scale, multi-ethnic genome-wide association study (GWAS). Methods: INHERENT brings together nine existing international or regional consortia in the field of haemoglobinopathies, namely ITHANET, RADeep, ARISE, SPARCO, SADaCC, REDAC, the HVP Global Globin Network, the International Health Repository, and the ClinGen Haemoglobinopathy VCEP. The activities of INHERENT are currently divided into five working groups, as follows: clinical, genotyping, data management and analysis, ethics, and knowledge translation. Participation in INHERENT is open for any group that can submit a minimum number of samples with their core phenotypic description. INHERENT membership is international and interdisciplinary and, currently, includes over 160 experts from 89 organisations, spanning 36 countries worldwide (Figure). INHERENT aims to recruit over 30,000 haemoglobinopathy patients, which is over one order of magnitude larger than any previous GWAS in the field. Summary: We demonstrate that the current membership of INHERENT has the potential to reach this sample size target. The large increase in the sample size and the diversity in the studied populations will enable novel discoveries and expand knowledge on haemoglobinopathy genetics, thus paving the way for advancing the science of personalised diagnosis and treatment.References 1. Kountouris P, et al, Am J Hematol 2021; Aug 18.
Covid-19: Antibody “signature” could predict risk of long covid
Authors: Jacqui Wise
Journal: BMJ (2022)

<h3>Summary</h3> Folding of proteins entering the mammalian secretory pathway requires the insertion of the correct disulfide bonds. Disulfide formation involves both an oxidative pathway for their insertion and a reductive pathway to remove incorrectly formed disulfides. Reduction of these disulfides is critical for correct folding and degradation of misfolded proteins. Previously, we showed that the reductive pathway is driven by NADPH generated in the cytosol. Here, by reconstituting the pathway using purified proteins and ER microsomal membranes, we demonstrate that the thioredoxin reductase system provides the minimal cytosolic components required for reducing proteins within the ER lumen. In particular, saturation of the pathway and its protease sensitivity demonstrates the requirement for a membrane protein to shuttle electrons from the cytosol to the ER lumen. These results provide compelling evidence for the critical role of the cytosol in regulating ER redox homeostasis to ensure correct protein folding and to facilitate the degradation of misfolded ER proteins.