tbuckley/cabot-search huggingface dataset:
Ibuprofen can mask symptoms of infection and might worsen outcomes, says European drugs agency
Authors: Ingrid Torjesen
Journal: BMJ (2020)

The European Medicines Agency’s pharmacovigilance risk assessment committee (PRAC) has recommended updating the product information for drugs containing ibuprofen and ketoprofen to warn that they can mask the symptoms of infection.

Such masking can delay treatment and worsen outcomes and has been observed in bacterial community acquired pneumonia and bacterial complications to varicella (chickenpox), the committee said after its monthly meeting on 17 April. Patients should therefore be monitored for worsening of infection when drugs containing ibuprofen and ketoprofen are used for relieving fever or pain from an infection.

The committee’s recommendation further fuels concerns about ibuprofen, which …
Early Signs of Thiamine Deficiency: A Case Report
Authors: Jorge C. Kattah
Journal: Annals of Internal Medicine (2020)

Letters7 July 2020Early Signs of Thiamine Deficiency: A Case ReportJorge C. Kattah, MDJorge C. Kattah, MDUniversity of Illinois College of Medicine, Peoria, Illinois (J.C.K.)Author, Article, and Disclosure Informationhttps://doi.org/10.7326/L19-0836 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Background: Recognition of early thiamine deficiency is necessary to avoid the risk for permanent neurologic deficits and early death. The Wernicke triad of encephalopathy, ataxia, and ophthalmoplegia (1) may be a late manifestation of thiamine deficiency. The Caine criteria require a history of malnutrition and 1 component of the Wernicke triad to consider the diagnosis of thiamine deficiency (2).Objective: To highlight "the earliest sign" of thiamine deficiency. Horizontal gaze–evoked nystagmus was the most common neurologic finding in large series of patients with thiamine deficiency (1, 3).Case Report: I was involved in the care of a 29-year-old woman with ...References1. Victor M, Adams RD, Collins G. The Wernicke–Korsakoff Syndrome. FA Davis. 1971. Google Scholar2. Caine D, Halliday GM, Kril JJ, et al. Operational criteria for the classification of chronic alcoholics: identification of Wernicke's encephalopathy. J Neurol Neurosurg Psychiatry. 1997;62:51-60. [PMID: 9010400] CrossrefMedlineGoogle Scholar3. De Wardener HE, Lennox B. Cerebral beriberi (Wernicke's encephalopathy); review of 52 cases in a Singapore prisoner-of-war hospital. Lancet. 1947;1:11-7. [PMID: 20278697] CrossrefMedlineGoogle Scholar4. Leigh RJ, Zee DS. The Neurology of Eye Movements. Oxford Univ Pr; 2015. Google Scholar5. Kattah JC, Dhanani SS, Pula JH, et al. Vestibular signs of thiamine deficiency during the early phase of suspected Wernicke encephalopathy. Neurol Clin Pract. 2013;3:460-468. [PMID: 30107022] doi:10.1212/01.CPJ.0000435749.32868.91 CrossrefMedlineGoogle Scholar Author, Article, and Disclosure InformationAffiliations: University of Illinois College of Medicine, Peoria, Illinois (J.C.K.)Disclosures: The author has disclosed no conflicts of interest. The form can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=L19-0836. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byDuodenal Adenocarcinoma in the Setting of Bariatric Surgery: A Perfect Storm for Wernicke's EncephalopathyClinical diagnosis, outcomes and treatment of thiamine deficiency in a tertiary hospitalA Case Report of Wernicke's Encephalopathy Associated With Schizophrenia Neuro-ophthalmic Manifestations of Wernicke Encephalopathy 7 July 2020Volume 173, Issue 1Page: 72-73KeywordsBrainstemCeliac diseaseLesionsMagnetic resonance imagingMigraineNeuronsNystagmusThiamineVomitingWalking ePublished: 28 April 2020 Issue Published: 7 July 2020 Copyright & PermissionsCopyright © 2020 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Distinct and shared contributions of diagnosis and symptom domains to cognitive performance in severe mental illness in the Paisa population: a case-control study
Authors: Susan K Service, Cristian Vargas Upegui, Mauricio Castaño Ramírez, Allison M Port, Tyler M Moore, Marfred Munoz Umanes, Luis Guillermo Agudelo Arango, Ana M Díaz-Zuluaga, Juanita Melo Espejo, María Cecilia López, Juan David Palacio, Sergio Ruiz Sánchez, Johanna Valencia, Terri M Teshiba, Alesandra Espinoza, Loes Olde Loohuis, Juan De la Hoz Gomez, Benjamin B Brodey, Chiara Sabatti, Javier I Escobar, Victor I Reus, Carlos Lopez Jaramillo, Ruben C Gur, Carrie E Bearden, Nelson B Freimer
Journal: The Lancet Psychiatry (2020)
Clinical course of coronavirus disease 2019 (COVID-19) in a series of 17 patients with systemic lupus erythematosus under long-term treatment with hydroxychloroquine
Authors: Alexis Mathian, Matthieu Mahevas, Julien Rohmer, Mathilde Roumier, Fleur Cohen-Aubart, Blanca Amador-Borrero, Audrey Barrelet, Cecile Chauvet, Thibaud Chazal, Michel Delahousse, Mathilde Devaux, Romain Euvrard, Jehane Fadlallah, Nans Florens, Julien Haroche, Miguel Hié, Laurent Juillard, Raphael Lhote, Thibault Maillet, Gaelle Richard-Colmant, Jean Baptiste Palluy, Micheline Pha, Laurent Perard, Philippe Remy, Etienne Rivière, Damien Sène, Pascal Sève, Capucine Morélot-Panzini, Jean-François Viallard, Jean-Simon Virot, Neila Benameur, Noël Zahr, Hans Yssel, Bertrand Godeau, Zahir Amoura
Journal: Annals of the Rheumatic Diseases (2020)

The current outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease 2019 (COVID-19) represents a source of concern for the management of patients with systemic lupus erythematosus (SLE). Indeed patients with SLE have an increased risk of severe infections due to intrinsic perturbations of their immune response, the use of immunosuppressive drugs, as well as the potential presence of organ damage associated with their disease. In this context, hydroxychloroquine (HCQ), a drug that is currently part of the long-term, standard-of-care treatment for SLE, has been reported to possess antiviral activity in vitro, and recent results from a preliminary clinical trial might support its use in curative or even prophylactic treatment for COVID-19.1–3 

During the first days of the COVID-19 outbreak in France, we launched an observational study with the aim to follow the clinical course of COVID-19 in patients with SLE who received long-term treatment with HCQ. To be eligible, patients with SLE had to (1) fulfil the 1997 criteria of the SLE classifications of the American College of Rheumatology or those of the 2019 European League Against Rheumatism/American College of Rheumatology4 5; (2) be on long-term treatment with HCQ; and (3) have SARS-CoV-2 carriage in their nasopharyngeal swab, as confirmed by real-time reverse transcription PCR analysis.

Data …
Diagnosis and Management of Squamous Cell Carcinoma of Unknown Primary in the Head and Neck: ASCO Guideline
Authors: Ellie Maghami, Nofisat Ismaila, Adriana Alvarez, Rebecca Chernock, Umamaheswar Duvvuri, Jessica Geiger, Neil Gross, Bruce Haughey, Doru Paul, Cristina Rodriguez, David Sher, Hilda E. Stambuk, John Waldron, Matt Witek, James Caudell
Journal: Journal of Clinical Oncology (2020)

PURPOSE To provide evidence-based recommendations to practicing physicians and other health care providers on the diagnosis and management of squamous cell carcinoma of unknown primary in the head and neck (SCCUP). METHODS The American Society of Clinical Oncology convened an Expert Panel of medical oncology, surgery, radiation oncology, radiology, pathology, and advocacy experts to conduct a literature search, which included systematic reviews, meta-analyses, randomized controlled trials, and prospective and retrospective comparative observational studies published from 2008 through 2019. Outcomes of interest included survival, local and regional disease control, and quality of life. Expert Panel members used available evidence and informal consensus to develop evidence-based guideline recommendations. RESULTS The literature search identified 100 relevant studies to inform the evidence base for this guideline. Four main clinical questions were addressed, which included subquestions on preoperative evaluations, surgical diagnostic and therapeutic procedures, appropriate pathology techniques, and adjuvant therapy. RECOMMENDATIONS Evidence-based recommendations were developed to address preoperative evaluation for patients with a neck mass, surgical diagnostic and therapeutic procedures, appropriate treatment options in unilateral versus bilateral SCCUP. Additional information is available at www.asco.org/head-neck-cancer-guidelines .
Maternal high-fat diet during lactation reprograms the dopaminergic circuitry in mice
Authors: R.N. Lippert, S. Hess, P. Klemm, L.M. Burgeno, T. Jahans-Price, M.E. Walton, P. Kloppenburg, J.C. Brüning
Journal: Journal of Clinical Investigation (2020)

The maternal perinatal environment modulates brain formation, and altered maternal nutrition has been linked to the development of metabolic and psychiatric disorders in the offspring. Here, we showed that maternal high-fat diet (HFD) feeding during lactation in mice elicits long-lasting changes in gene expression in the offspring's dopaminergic circuitry. This translated into silencing of dopaminergic midbrain neurons, reduced connectivity to their downstream targets, and reduced stimulus-evoked dopamine (DA) release in the striatum. Despite the attenuated activity of DA midbrain neurons, offspring from mothers exposed to HFD feeding exhibited a sexually dimorphic expression of DA-related phenotypes, i.e., hyperlocomotion in males and increased intake of palatable food and sucrose in females. These phenotypes arose from concomitantly increased spontaneous activity of D1 medium spiny neurons (MSNs) and profoundly decreased D2 MSN projections. Overall, we have unraveled a fundamental restructuring of dopaminergic circuitries upon time-restricted altered maternal nutrition to induce persistent behavioral changes in the offspring.
The Orally Available Selective Axl Inhibitor BGB324 Induces Diversification of the Immune Repertoire and Specific Changes in Plasma Biomarker Profiles
Authors: Sonja Loges, Bjørn Tore Gjertsen, Michael Heuser, Joerg Chromik, Isabel Ben-Batalla, Nuray Akyüz, David Micklem, Anthony Brown, James Lorens, Murray Yule, Maxim Kebenko, Melanie Janning, Mascha Binder, Walter Fiedler, Jorge E. Cortes
Journal: Blood (2017)
Medical Event
Authors: Soroush Zarehparvar Moghadam, Atena Aghaee, Mohamad Esmatinia, Navid Nateghi, Kamran Aryana
Journal: Clinical Nuclear Medicine (2020)

Abstract A 74-year-old woman with hyperthyroidism was referred for radioiodine therapy. The patient was accidentally given 60 mCi of 177 Lu-PSMA orally instead of 131 I. Upon discovery of this medical event, we immediately started radiation protective actions including hydration, antiemetics, and laxatives. The patients did not have any symptoms. Static acquisition was performed from the abdominal-pelvic and head and neck regions at 20 and 90 hours after ingestion, which showed prominent intestinal activity and mild systemic activity in the kidneys, bladder, salivary, and lacrimal glands.
Anti-proliferative effect of combining Letrozole with Sorafenib in MCF-7/Arom-1 breast cancer cells
Authors: Mara Bonelli, Claudia Fumarola, Roberta Alfieri, R Gatti, S Belletti, S La Monica, M Galetti, A Cavazzoni, A Frazzi, Alberto Bottini, Loredana Bergamini, Mark Lynch, Adrian Harris, Stephen Fox, Daniele Generali
Journal: Cancer Research (2008)

5441  INTRODUCTION: Many breast cancers (BC) either show de novo or develop acquired resistance after hormonal therapy with tamoxifen or aromatase inhibitors. Growth factor pathways have been implicated in this resistance. We have examined the effects of the aromatase inhibitor letrozole (L), approved for the treatment of hormone-dependent BC and sorafenib (S), a multi-kinase inhibitor recentlyapproved for the treatment ofadvanced renal cell carcinoma on cell-survival and proliferation using MCF-7/Arom-1 BC cells.  EXPERIMENTAL DESIGN: Effects of L and S on MCF-7/Arom-1 cell-survival and -proliferation were assessed by cell counting, MTT assay and clonogenic assay. Cell death was evaluated by FACS with Annexin V-FITC and PI staining and by confocal microscopy staining with calcein, DRAQ5 and PI. The phosphorylated form of the estrogen receptor α (pER α) and pERK1/2 were evaluated by Western blotting.  RESULTS: Treatment of MCF-7/Arom-1 cells with 1μM L reduced testosterone-driven cell proliferation, by inhibiting the synthesis of estrogens and thus preventing ERα activation. Sorafenib alone reduced MCF-7/Arom-1 cell proliferation in a concentration-dependent manner (IC50 3μM). The growth-inhibitory effect was associated with the induction of apoptosis, as indicated by FACS Annexin V-FITC assay and by confocal microscopy analysis, showing cells with rounded shape, nuclear condensation, membrane blebbing and calcein positivity until late stages. Apoptosis was not inhibited by the pan-caspase inhibitor z-VAD suggesting a caspase-independent mechanism of cell death.  The combined effect of L and S was then investigated. Sub-optimal concentrations of the drugs (1μM letrozole and 0.1-2.5 μM sorafenib) significantly enhanced the anti-proliferative effect observed with the single agents (p
Intratumoral Comparison of Nanoparticle Entrapped Docetaxel (CPC634) with Conventional Docetaxel in Patients with Solid Tumors
Authors: Florence Atrafi, Ruben A.G. van Eerden, Marte A.M van Hylckama Vlieg, Esther Oomen-de Hoop, Peter de Bruijn, Martijn P. Lolkema, Adriaan Moelker, Cristianne J. Rijcken, Rob Hanssen, Alex Sparreboom, Ferry A.L.M. Eskens, Ron H.J. Mathijssen, Stijn L.W. Koolen
Journal: Clinical Cancer Research (2020)

Abstract Purpose: CPC634 is a novel nanoparticle entrapping docetaxel, developed to enhance the intratumoral chemotherapy exposure. This randomized cross-over study compared the intratumoral and plasma pharmacokinetics of CPC634 with conventional docetaxel. Patients and Methods: Adult patients with solid tumors were randomized to receive CPC634 (75 mg/m2) in cycle 1, and conventional docetaxel (75 mg/m2) in cycle 2 or vice versa. The study was powered to identify a 25% increase of intratumoral total docetaxel exposure after CPC634 infusion compared with conventional docetaxel. Four patients were allocated per tumor sampling time point, that is, 24, 48, 72, and 96 hours, 7 and 14 days after infusion during both cycles. Total docetaxel and released docetaxel from the nanoparticle were determined in tumor tissue derived from a metastatic lesion and in plasma. Pharmacokinetic data were analyzed using linear mixed modeling. Results: In total, 24 evaluable patients were included. In the tumor, CPC634 exhibited a 461% higher total docetaxel (P &amp;lt; 0.001) and a comparable released docetaxel concentration (P = 0.43). Plasma AUCinf was 27% higher (P = 0.001) and Cmax was 91% lower (P &amp;lt; 0.001) for CPC634 released docetaxel. The median observed neutrophil count nadir after conventional docetaxel treatment was lower (0.50 × 109/L) compared with CPC634 (4.30 × 109/L; P &amp;lt; 0.001). Conclusions: Here, we demonstrated that CPC634 enhanced the intratumoral total docetaxel exposure compared with conventional docetaxel. The lower incidence of neutropenia during CPC634 treatment is presumably related to lower plasma Cmax of released docetaxel. The unique pharmacokinetic profile of CPC634 nanoparticles has the potential to improve docetaxel treatment. A phase II efficacy trial of CPC634 is currently ongoing.
Targeting glutamine metabolism enhances tumor-specific immunity by modulating suppressive myeloid cells
Authors: Min-Hee Oh, Im-Hong Sun, Liang Zhao, Robert D. Leone, Im-Meng Sun, Wei Xu, Samuel L. Collins, Ada J. Tam, Richard L. Blosser, Chirag H. Patel, Judson M. Englert, Matthew L. Arwood, Jiayu Wen, Yee Chan-Li, Lukáš Tenora, Pavel Majer, Rana Rais, Barbara S. Slusher, Maureen R. Horton, Jonathan D. Powell
Journal: Journal of Clinical Investigation (2020)

Myeloid cells comprise a major component of the tumor microenvironment (TME) that promotes tumor growth and immune evasion. By employing a small-molecule inhibitor of glutamine metabolism, not only were we able to inhibit tumor growth, but we markedly inhibited the generation and recruitment of myeloid-derived suppressor cells (MDSCs). Targeting tumor glutamine metabolism led to a decrease in CSF3 and hence recruitment of MDSCs as well as immunogenic cell death, leading to an increase in inflammatory tumor-associated macrophages (TAMs). Alternatively, inhibiting glutamine metabolism of the MDSCs themselves led to activation-induced cell death and conversion of MDSCs to inflammatory macrophages. Surprisingly, blocking glutamine metabolism also inhibited IDO expression of both the tumor and myeloid-derived cells, leading to a marked decrease in kynurenine levels. This in turn inhibited the development of metastasis and further enhanced antitumor immunity. Indeed, targeting glutamine metabolism rendered checkpoint blockade-resistant tumors susceptible to immunotherapy. Overall, our studies define an intimate interplay between the unique metabolism of tumors and the metabolism of suppressive immune cells.
Molecular imaging of inflammation - Current and emerging technologies for diagnosis and treatment
Authors: Neil MacRitchie, Marina Frleta-Gilchrist, Atsuko Sugiyama, Tristan Lawton, Iain B. McInnes, Pasquale Maffia
Journal: Pharmacology & Therapeutics (2020)

Inflammation is a key factor in multiple diseases including primary immune-mediated inflammatory diseases e.g. rheumatoid arthritis but also, less obviously, in many other common conditions, e.g. cardiovascular disease and diabetes. Together, chronic inflammatory diseases contribute to the majority of global morbidity and mortality. However, our understanding of the underlying processes by which the immune response is activated and sustained is limited by a lack of cellular and molecular information obtained in situ. Molecular imaging is the visualization, detection and quantification of molecules in the body. The ability to reveal information on inflammatory biomarkers, pathways and cells can improve disease diagnosis, guide and monitor therapeutic intervention and identify new targets for research. The optimum molecular imaging modality will possess high sensitivity and high resolution and be capable of non-invasive quantitative imaging of multiple disease biomarkers while maintaining an acceptable safety profile. The mainstays of current clinical imaging are computed tomography (CT), magnetic resonance imaging (MRI), ultrasound (US) and nuclear imaging such as positron emission tomography (PET). However, none of these have yet progressed to routine clinical use in the molecular imaging of inflammation, therefore new approaches are required to meet this goal. This review sets out the respective merits and limitations of both established and emerging imaging modalities as clinically useful molecular imaging tools in addition to potential theranostic applications.
Vaccines and Broadly Neutralizing Antibodies for HIV-1 Prevention
Authors: Kathryn E. Stephenson, Kshitij Wagh, Bette Korber, Dan H. Barouch
Journal: Annual Review of Immunology (2020)

Development of improved approaches for HIV-1 prevention will likely be required for a durable end to the global AIDS pandemic. Recent advances in preclinical studies and early phase clinical trials offer renewed promise for immunologic strategies for blocking acquisition of HIV-1 infection. Clinical trials are currently underway to evaluate the efficacy of two vaccine candidates and a broadly neutralizing antibody (bNAb) to prevent HIV-1 infection in humans. However, the vast diversity of HIV-1 is a major challenge for both active and passive immunization. Here we review current immunologic strategies for HIV-1 prevention, with a focus on current and next-generation vaccines and bNAbs.
Association of the US Food and Drug Administration Antipsychotic Drug Boxed Warning With Medication Use and Health Outcomes in Elderly Patients With Dementia
Authors: Annalisa Rubino, Myrlene Sanon, Michael L. Ganz, Alex Simpson, Miriam C. Fenton, Sumit Verma, Ann Hartry, Ross A. Baker, Ruth A. Duffy, Keva Gwin, Howard Fillit
Journal: JAMA Network Open (2020)

Atypical antipsychotics (AAPs) are often used off-label to manage dementia-associated neuropsychiatric symptoms. In 2005, the US Food and Drug Administration (FDA) issued a boxed warning for the use of AAPs in elderly patients. The long-term association of this warning with health outcomes is unknown to date.To assess the long-term association of the 2005 FDA boxed warning on AAPs with psychiatric medication and opioid use, health events, and quality of life among elderly individuals with dementia.For this cross-sectional study, data were analyzed from the household component of the Medical Expenditure Panel Survey (MEPS), the National Ambulatory Medical Care Survey (NAMCS), and the National Hospital Ambulatory Medical Care Survey (NHAMCS) fielded between January 1, 1996, and December 31, 2014. This interrupted time-series analysis applied to 3-year moving means derived from the 1996-2014 MEPS, NAMCS, and NHAMCS. All survey respondents included in this analysis were 65 years or older and had dementia. Data analysis was performed from December 1, 2017, to March 15, 2018.The 2005 FDA boxed warning on AAPs.Use of psychiatric medications and opioids, prevalence of cerebrovascular and cardiovascular events, prevalence of falls and/or fractures, 2-year mortality, and health-related quality of life assessed by the Medical Outcomes Study 12-Item Short-Form Health Survey scores.A total of 2430 (MEPS) and 5490 (NAMCS and NHAMCS) respondents were identified, corresponding to weighted populations of 22 996 526 (MEPS) and 65 502 344 (NAMCS and NHAMCS) noninstitutionalized elderly individuals with dementia (mean [SD] age, 81.06 [1.13] years; 63.1% female). In the MEPS sample, compared with before 2005, AAP use (from an annual slope of 0.99 to -0.18 percentage points), cerebrovascular events (0.75 to -0.50 percentage points), and falls and/or fractures (-1.72 to -0.40 percentage points) decreased and opioid use (0.04 to 1.29 percentage points), antiepileptic use (-0.42 to 1.21 percentage points), cardiovascular events (-0.13 to 1.30 percentage points), and 2-year mortality risk (-0.68 to 0.18 percentage points) increased. Health-related quality of life remained relatively unchanged. The NAMCS and NHAMCS sample yielded similar findings.These data suggest that the 2005 FDA boxed warning was associated with some unintended negative patient outcomes.
Versican (VCAN) Proteolysis Predicts T-Cell Infiltration in Myeloma Bone Marrow Post- Autologous Stem Cell Transplant (ASCT)
Authors: Adam Pagenkopf, Binod Dhakal, Chelsea L. Hope, Athanasios Papadas, Michael G Johnson, Bradley Nagel, Elena Kurudza, Samik Partha, Bianca Ruffolo, Catherine Leith, Shigeki Miyamoto, Peiman Hematti, Parameswaran Hari, Natalie Scott Callander, Fotios Asimakopoulos
Journal: Blood (2017)
CircAtlas: an integrated resource of one million highly accurate circular RNAs from 1070 vertebrate transcriptomes
Authors: Wanying Wu, Peifeng Ji, Fangqing Zhao
Journal: Genome biology (2020)

Abstract Existing circular RNA (circRNA) databases have become essential for transcriptomics. However, most are unsuitable for mining in-depth information for candidate circRNA prioritization. To address this, we integrate circular transcript collections to develop the circAtlas database based on 1070 RNA-seq samples collected from 19 normal tissues across six vertebrate species. This database contains 1,007,087 highly reliable circRNAs, of which over 81.3% have been assembled into full-length sequences. We profile their expression pattern, conservation, and functional annotation. We describe a novel multiple conservation score, co-expression, and regulatory networks for circRNA annotation and prioritization. CircAtlas can be accessed at http://circatlas.biols.ac.cn/ .