tbuckley/cabot-search huggingface dataset:
Candidate rheumatologic treatments for COVID-19. Response to: ‘COVID-19 infection in a patient with FMF: does colchicine have a protective effect?’ by Kobak
Authors: Sara Monti, Carlomaurizio Montecucco
Journal: Annals of the Rheumatic Diseases (2020)

<h3>Abstract</h3> Capturing individual differences in cognition is central to human neuroscience. Yet our ability to estimate cognitive abilities via brain MRI is still poor in both prediction and reliability. Our study tested if this inability can be improved by integrating MRI signals across the whole brain and across modalities, including task-based functional MRI (tfMRI) of different tasks along with other non-task MRI modalities, such as structural MRI, resting-state functional connectivity. Using the Human Connectome Project (n=873, 473 females, after quality control), we directly compared predictive models comprising different sets of MRI modalities (e.g., seven tasks vs. non-task modalities). We applied two approaches to integrate multimodal MRI, stacked vs. flat models, and implemented 16 combinations of machine-learning algorithms. The stacked model integrating all modalities via stacking Elastic Net provided the best prediction (<i>r</i>=.57), relatively to other models tested, as well as excellent test-retest reliability (ICC=<sup>~</sup>.85) in capturing general cognitive abilities. Importantly, compared to the stacked model integrating across non-task modalities (<i>r</i>=.27), the stacked model integrating tfMRI across tasks led to significantly higher prediction (<i>r</i>=.56) while still providing excellent test-retest reliability (ICC=<sup>~</sup>.83). The stacked model integrating tfMRI across tasks was driven by frontal and parietal areas and by tasks that are cognition-related (working-memory, relational processing, and language). This result is consistent with the parieto-frontal integration theory of intelligence. Accordingly, our results contradict the recently popular notion that tfMRI is not reliable enough to capture individual differences in cognition. Instead, our study suggests that tfMRI, when used appropriately (i.e., by drawing information across the whole brain and across tasks and by integrating with other modalities), provides predictive and reliable sources of information for individual differences in cognitive abilities, more so than non-task modalities. <h3>Highlights</h3> Non-task MRI (sMRI, rs-fMRI) are often used for the brain-cognition relationship. Task-based fMRI has been deemed unreliable for capturing individual differences. We tested if drawing task-based fMRI information across regions/tasks improves prediction and reliability of the brain-cognition relationship. Our approach boosts prediction of task-based fMRI over non-task MRI. Our approach renders task-based fMRI reliable over time. Our approach shows the importance of the fronto-parietal areas in cognition.
Intratumoral γδ T‐Cell Infiltrates, Chemokine (C‐C Motif) Ligand 4/Chemokine (C‐C Motif) Ligand 5 Protein Expression and Survival in Patients With Hepatocellular Carcinoma
Authors: Na Zhao, Hien Dang, Lichun Ma, Sean P. Martin, Marshonna Forgues, Kris Ylaya, Stephen M. Hewitt, Xin Wei Wang
Journal: Hepatology (2020)

Background and Aims Hepatocellular carcinoma (HCC) is an aggressive malignancy which is often associated with a complex tumor microenvironment attributable to etiology‐induced cellular inflammation. γδ T cells are known to detect and react to chronic inflammation, which is linked to cancer development, progression, and metastasis. Our recent genomic study revealed an increased infiltration of several immune cell types, including γδ T cells, in tumor microenvironments of a Thai HCC subtype associated with a good prognosis. Approach and Results Here, we quantified the amount of γδ T cells using a γδ T‐cell‐specific gene signature in 247 Chinese HCC patients. We also validated the γδ T‐cell signature in American HCC patients. Additionally, such an association was only found in tumor transcriptomic data, but not in adjacent nontumor transcriptomic data, suggesting a selective enrichment of γδ T cells in the tumor microenvironment. Moreover, the γδ T‐cell signature was positively correlated with the expression of natural killer cell receptor genes, such as NKG2D and cytolytic T‐cell genes granzymes and perforin, suggesting a stronger T‐cell‐mediated cytotoxic activity. Furthermore, we found that the γδ T‐cell‐specific gene expression is positively correlated with the expression of chemokine (C‐C motif) ligand 4 (CCL4)/chemokine (C‐C motif) ligand 5 (CCL5) and C‐C chemokine receptor type 1 (CCR1)/C‐C chemokine receptor type 5 (CCR5), the receptors for γδ T cells. We validated these results using immunohistochemical analysis of formalin‐fixed, paraffin‐embedded tumor biopsies from 182 HCC patients. Moreover, we found evidence of CCL4/CCL5‐mediated recruitment of γδ T cells both in vitro and in a murine orthotopic Hepa1‐6 HCC model. Conclusions We propose that CCL4/CCL5 may interact with their receptor, CCR1/CCR5, which may facilitate the recruitment of γδ T cells from peripheral blood or peritumor regions to the tumor regions. Consequently, an increasing infiltration of γδ T cells in tumors may enhance antitumor immunity and improve patients’ prognosis.
Abstract A52: Deciphering MET-dependent modulation of global cellular responses to DNA damage by quantitative phosphoproteomics reveals Ser1016 as a novel MET phosphosite that regulates cellular response to irradiation
Authors: Jonas P. Koch, Ariel Bensimon, Selina M. Roth, Matúš Medo, Paola Francica, Eleonora Orlando, Rahel Riedo, Jacopo Gavini, Aurélie Quintin, Astrid A. Glück, Deborah M. Stroka, Andree Blaukat, Daniel M. Aebersold, Yitzhak Zimmer, Ruedi Aebersold, Michaela Medová
Journal: Cancer Research (2020)

Abstract There is emerging evidence that DNA damage response (DDR) intertwines with signaling pathways downstream of oncogenic receptor tyrosine kinases (RTKs). Two complementary phosphoproteomic approaches revealed global networks and identified and validated core phosphosites that participate in a crosstalk between the MET RTK and the DDR, including a newly discovered phosphosite on MET itself, Ser1016. DNA-PK phosphorylates Ser1016, and this phosphorylation is increased following irradiation. Cell lines as well as animal models expressing Ser1016Ala phosphodeficient receptor exhibit greater sensitivity to irradiation. MET Ser1016Ala mutants fail to undergo proper radiation-induced cell cycle arrest by bypassing the G2 checkpoint with a premature entry into mitosis and abnormal mitotic spindles, leading to a lower proliferation rate of Ser1016-deficient cells. Regulation of MET activity through Ser1016 phosphorylation by a DDR core kinase represents a critical event involved in DNA repair signaling through a growth factor receptor that frequently functions as a tumor driver. Citation Format: Jonas P. Koch, Ariel Bensimon, Selina M. Roth, Matúš Medo, Paola Francica, Eleonora Orlando, Rahel Riedo, Jacopo Gavini, Aurélie Quintin, Astrid A. Glück, Deborah M. Stroka, Andree Blaukat, Daniel M. Aebersold, Yitzhak Zimmer, Ruedi Aebersold, Michaela Medová. Deciphering MET-dependent modulation of global cellular responses to DNA damage by quantitative phosphoproteomics reveals Ser1016 as a novel MET phosphosite that regulates cellular response to irradiation [abstract]. In: Proceedings of the AACR Special Conference on the Evolving Landscape of Cancer Modeling; 2020 Mar 2-5; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2020;80(11 Suppl):Abstract nr A52.
Phosphodiesterase inhibition as an approach to increase chemosensitivity of prostate cancer
Authors: Genevieve Pare, Jenny Jun, Klodiana Gjoncaj, Erin Bell, Nianping Hu, Charles Graham, D Siemens
Journal: Cancer Research (2008)

691  Purpose: Low tumour oxygenation (hypoxia) correlates with resistance to chemotherapeutic agents. We have recently provided evidence that hypoxia-induced resistance to anti-cancer drugs can be decreased by stimulating nitric oxide (NO) signalling through a cGMP-mediated pathway. An alternative approach to increase the activity of this signalling pathway is to prevent the breakdown of cGMP by phosphodiesterases (PDEs). The aim of this study was to determine whether PDE inhibitors are capable of attenuating hypoxia-induced chemoresistance in prostate carcinoma cells.  Materials and Methods: Western blots, immunohistochemistry and functional enzymatic assays were used to determine the expression of PDEs in human cell lines and human prostate cancer samples. Drug sensitivity assays of cell lines exposed to hypoxic or standard conditions were performed in the presence of various concentrations of the PDE-5-specific inhibitor zaprinast.  Results: These studies revealed the presence of two of the multiple cGMP-specific PDEs (PDE5 and PDE11A) in both DU145 and PC-3 cell lines and in prostate cancer tissue. Clonogenic assays revealed that incubation of DU145 in 0.5% O2 for 24 hours resulted in a corresponding 4-fold increase (P
Evaluating the massive underreporting and undertesting of COVID-19 cases in multiple global epicenters
Authors: H. Lau, T. Khosrawipour, P. Kocbach, H. Ichii, J. Bania, V. Khosrawipour
Journal: Pulmonology (2020)

With continuous global COVID-19 outbreak, differing case numbers and mortality rates are observed. While actual case numbers appear vague, mortality numbers related to COVID-19 seem more precise. In this study, we used the mortality rate as the main indicator to evaluate the extent of underreporting and underdetection of COVID-19 cases. We have analyzed all available data provided by the World Health Organization on the development of international COVID-19 cases and mortality numbers on March 17th, 2020. A crude case-fatality risk (cCFR) and adjusted case-fatality risk (aCFR) was calculated for China, South Korea, Japan, Italy, France, Spain, Germany, Iran and the United States. Additionally, a fold-change (FC) was derived for each country. The highest aCFR and FC were detected for Spain. Based on their FC values, an extremely high number of undetected COVID-19 cases was displayed in France, the United States, Italy and Spain. For these countries, our findings indicate a detection rate of only 1–2% of total actual COVID-19 cases. Due to limited testing capacities, mortality numbers may serve as a better indicator for COVID-19 case spread in many countries. Our data indicate that countries like France, Italy, the United States, Iran and Spain have extremely high numbers of undetected and underreported cases. Differences in testing availability and capacity, containment as well as overall health care and medical infrastructure result in significantly different mortality rates and COVID-19 case numbers for each respective country.
Screening for Drug Use in Primary Care
Authors: Katharine A. Bradley, Gwen T. Lapham, Amy K. Lee
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
Health screening of resettled Indochinese refugees - Washington, DC, Utah.
Authors: E. Boudreau, E. B. Doberstyn, A. Colon, L. Tina, P. McClelland, M. E. Levy, E. Haws, H. L. Gibbons, K. Mathews, M. W. Kehrberg
Journal: MMWR Morbidity and Mortality Weekly Report (1980)
Re-evaluating the role of isoniazid in treatment of pulmonary tuberculosis
Authors: Scott Heysell, Stellah Mpgama
Journal: The Lancet Microbe (2020)

For more than half a century, isoniazid has served as a principal component of combination drug regimens to treat tuberculosis. Selective in spectrum to mycobacteria, isoniazid primarily inhibits mycolic acid synthesis thereby disrupting cell wall construction, and has shown the greatest bactericidal effect against populations of Mycobacterium tuberculosis in the logarithmic growth phase.1 The early bactericidal activity (EBA) of isoniazid was first examined in humans with tuberculosis by Jindani and colleagues,2 and their work has since informed tuberculosis therapeutics by defining the crucial role of isoniazid during the initial days of tuberculosis treatment and its contribution to long-term treatment success.
SAT0459 EVALUATION OF THE PREVALENCE AND THE MANAGEMENT OF OSTEOPOROTIC FRACTURES IN PATIENTS HOSPITALIZED AT NANCY UNIVERSITY HOSPITAL (FRANCE) IN 2017.
Authors: A. Baccichetti, P. L. Nguyen-Thi, A. Blum, D. Mainard, F. Sirveaux, L. Nace, A. Valance, T. Civit, G. Dautel, C. Perret-Guillaume, B. Guerci, H. Tronel, I. Chary Valckenaere, D. Loeuille
Journal: Annals of the Rheumatic Diseases (2020)

Background: Osteoporotic fractures are a major public health concern because of their consequences in morbidity, costs and mortality. In the meantime, historically postfracture osteoporosis medication use rates have been poor. Objectives: The aim is to analyze the management of osteoporosis in patients hospitalized for osteoporotic fractures (OF) at Nancy University Hospital (France) in 2017. Methods: Total number of hospitalized patients and hospital stays were extracted by the Department of Medical Information (DIM) which selected departments with at least forty hospitalizations with Medical Unit Summary related to a diagnosis of fracture or osteoporosis. Hospitalizations not concerned by a recent OF were excluded. Data on fractures, patient characteristics, risk factors for OF and fall, management of osteoporosis, discharge status, stay duration, were studied from patient medical records. Prevalence of OF stays, management of osteoporosis and factors associated with duration of stay were analyzed. Results: Out of a total of 153,840 hospitalizations, 918 hospitalizations (844 patients, mean age 74.5 years ± 13.6, 74.5% women) concern an OF. The prevalence of hospitalizations for OF was 0.6% of total hospitalizations and 17.9% of total hospitalizations for fractures. Among the 844 patients, 85.7% had a severe fracture (vertebral fracture: 56.2%, hip fracture: 24.1%), 16.5% had a non-severe fracture, and 8.5% had a fracture cascade in the year. At discharge from hospital, 11.7% of patients received a specific treatment for osteoporosis. Longer stay duration was associated with age, severe fractures, Groll index and discharge status. Conclusion: Nearly one hospitalized fracture in five is osteoporotic, while only one in ten patients is treated for osteoporosis. Stay duration increased with age and comorbidities. This encourages the development of early prevention, screening and treatment strategies for osteoporosis. References: [1]Hernlund E, Svedbom A, Ivergård M, Compston J, Cooper C, Stenmark J, et al. Osteoporosis in the European Union: medical management, epidemiology and economic burden. A report prepared in collaboration with the International Osteoporosis Foundation (IOF) and the European Federation of Pharmaceutical Industry Associations (EFPIA). Arch Osteoporos. 2013;8:136. [2]Johnell O, Kanis JA. An estimate of the worldwide prevalence and disability associated with osteoporotic fractures. Osteoporos Int. 2006 Oct 19;17(12):1726–33. [3]Giangregorio L, Papaioannou A, Cranney A, Zytaruk N, Adachi JD. Fragility Fractures and the Osteoporosis Care Gap: An International Phenomenon. Semin Arthritis Rheum. 2006 Apr;35(5):293–305. Disclosure of Interests: None declared
AB0256 INCREASED SERUM PROCALCITONIN CONCENTRATION IN PATIENTS WITH RHEUMATOID ARTHRITIS FREE OF ACTIVE INFECTION
Authors: K. J. Ng, K. Y. Huang, C. H. Tung, M. C. Lu, N. S. Lai
Journal: Annals of the Rheumatic Diseases (2020)

Background: Rheumatoid arthritis (RA) is the most common inflammatory arthritis, affecting 0.5-1% of the general population worldwide. Patients with RA are often in a relatively immunocompromised status. Previous study have evaluated procalcitonin (PCT) application among autoimmune and autoinflammatory diseases for the diagnosis of systemic bacterial infection (1, 2) To date, the correlation of baseline PCT levels and RA disease activities, different treatment, or the expression of proinflammatory cytokines in patients with RA remained unknown. Objectives: To investigate the baseline PCT levels among patients with RA without active infection compared with healthy controls and to understand the relationship of PCT with RA disease activity, treatment received by patients, and the expression of proinflammatory cytokines. Methods: Patients aged 20 years and above, with clinician-confirmed diagnosis of RA were included during regular outpatient visits. RA disease activity was measured using the DAS28-ESR. Results: A total of 623 patients with RA and 40 healthy subjects were recruited in this study. The mean PCT were significantly higher in patients with RA (6.90 ± 11.81 * 10 -3 ng/mL) compared with healthy controls (1.14 ± 3.26 * 10 -3 ng/mL) (p = 0.002). After adjusted for age and sex, the PCT levels remain significantly elevated in patients with RA (p = 0.001). PCT was not significantly correlated with biologic agent, age, sex, disease duration, disease activity, C-reactive protein, conventional synthetic disease-modifying antirheumatic drugs (csDMARD), and comorbidities. Multiple linear regression analysis showed that PCT was inversely associated with the expression of IL-1β (B = −0.883; CI 95% −1.388, −0.378, p = 0.001) and IFN-α (B = −1.197; CI 95% −2.153, −0.242, p = 0.014) after adjusted for age and sex. Conclusion: Patients with RA have significantly higher baseline PCT compared with healthy controls. The treatment received by patients with RA did not affect the level of PCT. Further investigation is required to determine the optimal cutoff value of PCT among patients with RA before applying it in daily clinical practice. References: [1]Scire CA, Cavagna L, Perotti C, Bruschi E, Caporali R, Montecucco C. Diagnostic value of procalcitonin measurement in febrile patients with systemic autoimmune diseases. Clin Exp Rheumatol. 2006;24(2):123−8. [2]Delevaux I, Andre M, Colombier M, Albuisson E, Meylheuc F, Begue RJ, et al. Can procalcitonin measurement help in differentiating between bacterial infection and other kinds of inflammatory processes? Ann Rheum Dis. 2003;62(4):337−40. Acknowledgments: The authors gratefully acknowledge Dr. Malcolm Koo for advice on statistical analysis and manuscript preparation. Disclosure of Interests: None declared
Case 18-2020: A 73-Year-Old Man with Hypoxemic Respiratory Failure and Cardiac Dysfunction
Authors: Dhruv S. Kazi, Lila M. Martin, Diana Litmanovich, Duane S. Pinto, Kevin J. Clerkin, Peter J. Zimetbaum, David M. Dudzinski
Journal: New England Journal of Medicine (2020)

A Man with Respiratory Failure and Cardiac Dysfunction A 73-year-old man presented with progressive cough, fatigue, fevers, and dyspnea during the Covid-19 pandemic; he received mechanical ventilat...
A study of the drug tildrakizumab for plaque psoriasis
Authors: A.B. Kimball, K.A. Papp, K. Reich, M. Gooderham, Q. Li, N. Cichanowitz, C. La Rosa, A. Blauvelt
Journal: British Journal of Dermatology (2020)

Tildrakizumab is a fairly new type of medicine called a biologic, used for the treatment of moderate‐to‐severe psoriasis. The drug prevents the action of a specific molecule in the body involved in inflammation, known as cytokine interleukin (IL)‐23p19. Previous studies have shown it to be superior to a placebo (an inactive substance, like a “sugar pill”) and to an older biologic drug, the TNF inhibitor etanercept. However, trials rarely reflect real‐world experience, where patients may switch from one drug to another, change drug dosage or interrupt treatment, e.g. because of an infection. The authors, based in U.S.A., Canada and Germany, reviewed results from two studies, one comparing two different doses of tildrakizumab (100mg or 200mg per day) with placebo, and the other comparing it with etanercept, including a total of 1862 adults with moderate‐to‐severe plaque psoriasis. Treatments were re‐randomised during the course of the study. They found that the response to tildrakizumab was sustained (meaning it kept working), without the secondary failure (decreasing responsiveness to a drug after an initial satisfactory response) seen in some patients on etanercept, and the drug regained effective control of the psoriasis after treatment was interrupted. Overall the drug was well tolerated, meaning that side effects were minimal. This is a summary of the study: Efficacy and safety of tildrakizumab for plaque psoriasis with continuous dosing, treatment interruption, dose adjustments and switching from etanercept: results from phase III studies
NHS blood unit is “systemically racist” and “psychologically unsafe,” investigation finds
Authors: Gareth Iacobucci
Journal: BMJ (2020)

An independent investigation into working conditions at a unit of the NHS’s blood and organ transplant service has concluded that it is “systemically racist” and “psychologically unsafe.”

The internal investigation1 was commissioned in response to numerous complaints from ethnic minority staff working in a unit of NHS Blood and Transplant (NHSBT) in Colindale, north London. The report, carried out by the workplace relations company Globis Mediation Group, concluded that the environment was “toxic” and “dysfunctional.”

The report found evidence that ethnic minority employees had faced discrimination when applying for jobs and that white candidates had been selected for posts ahead of black applicants who …