tbuckley/cabot-search huggingface dataset:
Identification of FABP5 as an immunometabolic marker in human hepatocellular carcinoma
Authors: Fangming Liu, Weiren Liu, Shuang Zhou, Chunhui Yang, Mengxin Tian, Guangshuai Jia, Han Wang, Bijun Zhu, Mingxiang Feng, Yan Lu, Tiankui Qiao, Xinxin Wang, Wei Cao, Xiangdong Wang, Yinghong Shi, Duojiao Wu
Journal: Journal for ImmunoTherapy of Cancer (2020)

Background Regulating T-cell metabolism is crucial for their anticancer activity. Therefore, understanding the function and metabolism of human tumor-infiltrating T cells is of broad interest and clinical importance. Methods CD3 + CD45 + T cells were sorted from adjacent area or tumor core of human hepatocellular carcinoma (HCC), then the clusters and heterogeneity of T cells were further interrogated by single-cell transcriptomic profiling. 118 surgical samples from patients with HCC were histologically examined for infiltration of CD8 + T cells in tumor and adjacent tissue. Results Single-cell transcriptomic profiling indicated that several exhausted T-cell (Tex) populations differentially coexisted in the tumor and adjacent tissue. CD137 identifies and enriches Tex with superior effector functions and proliferation capacity. Furthermore, enhanced fatty acid-binding protein 5 (FABP5) expression along with increased mitochondrial oxidative metabolism were evident in these CD137-enriched Tex. Inhibiting FABP5 expression and mitochondrial fatty acid oxidation impaired the anti-apoptosis and proliferation of CD137-enriched Tex. These observations have been verified by generating CD137 CART. Immunohistochemistry staining on the tissue microarray of 118 patients with HCC showed intra-tumoral FABP5 high CD8 + T-cell infiltration was linked to overall and recurrence-free survival. Conclusions The tumor microenvironment can impose metabolic restrictions on T-cell function. CD137, a costimulatory molecule highly expressed on some Tex, uses exogenous fatty acids and oxidative metabolism to mediate antitumor immunity. The immunometabolic marker FABP5 should be investigated in larger, longitudinal studies to determine their potential as prognostic biomarkers for HCC.
Effect of Probiotic Use on Antibiotic Administration Among Care Home Residents
Authors: Christopher C. Butler, Mandy Lau, David Gillespie, Eleri Owen-Jones, Mark Lown, Mandy Wootton, Philip C. Calder, Antony J. Bayer, Michael Moore, Paul Little, Jane Davies, Alison Edwards, Victoria Shepherd, Kerenza Hood, F. D. Richard Hobbs, Mina Davoudianfar, Heather Rutter, Helen Stanton, Rachel Lowe, Richard Fuller, Nick A. Francis
Journal: JAMA (2020)

Probiotics are frequently used by residents in care homes (residential homes or nursing homes that provide residents with 24-hour support for personal care or nursing care), although the evidence on whether probiotics prevent infections and reduce antibiotic use in these settings is limited.To determine whether a daily oral probiotic combination of Lactobacillus rhamnosus GG and Bifidobacterium animalis subsp lactis BB-12 compared with placebo reduces antibiotic administration in care home residents.Placebo-controlled randomized clinical trial of 310 care home residents, aged 65 years and older, recruited from 23 care homes in the United Kingdom between December 2016 and May 2018, with last follow-up on October 31, 2018.Study participants were randomized to receive a daily capsule containing a probiotic combination of Lactobacillus rhamnosus GG and Bifidobacterium animalis subsp lactis BB-12 (total cell count per capsule, 1.3 × 1010 to 1.6 × 1010) (n = 155), or daily matched placebo (n = 155), for up to 1 year.The primary outcome was cumulative antibiotic administration days for all-cause infections measured from randomization for up to 1 year.Among 310 randomized care home residents (mean age, 85.3 years; 66.8% women), 195 (62.9%) remained alive and completed the trial. Participant diary data (daily data including study product use, antibiotic administration, and signs of infection) were available for 98.7% randomized to the probiotic group and 97.4% randomized to placebo. Care home residents randomized to the probiotic group had a mean of 12.9 cumulative systemic antibiotic administration days (95% CI, 0 to 18.05), and residents randomized to placebo had a mean of 12.0 days (95% CI, 0 to 16.95) (absolute difference, 0.9 days [95% CI, -3.25 to 5.05]; adjusted incidence rate ratio, 1.13 [95% CI, 0.79 to 1.63]; P = .50). A total of 120 care home residents experienced 283 adverse events (150 adverse events in the probiotic group and 133 in the placebo group). Hospitalizations accounted for 94 of the events in probiotic group and 78 events in the placebo group, and deaths accounted for 33 of the events in the probiotic group and 32 of the events in the placebo group.Among care home residents in the United Kingdom, a daily dose of a probiotic combination of Lactobacillus rhamnosus GG and Bifidobacterium animalis subsp lactis BB-12 did not significantly reduce antibiotic administration for all-cause infections. These findings do not support the use of probiotics in this setting.ISRCTN Identifier:16392920.
Response to: ‘Concerns and needs of patients with systemic lupus erythematosus regarding hydroxychloroquine supplies during the COVID-19 pandemic: results from a patient-centred survey’ by Plüß <i>et al</i>
Authors: Alexis Mathian, Zahir Amoura
Journal: Annals of the Rheumatic Diseases (2020)

The inflammatory neuropathies are a large diverse group of immune-mediated neuropathies that are amenable to treatment and may be reversible. Their accurate diagnosis is essential for informing the patient of the likely course and prognosis of the disease, informing the treating physician of the appropriate therapy and informing the scientific community of the results of well-targeted, designed and performed clinical trials. With the advent of biological therapies able to manipulate the immune response more specifically, an understanding of the pathogenesis of these conditions is increasingly important. This review presents a broad overview of the pathogenesis, diagnosis and therapy of inflammatory neuropathies, concentrating on the most commonly encountered conditions.
Phenoxodiol a chemosensitizer in taxotere-resistant ovarian cancer cells
Authors: Gil Mor, Wei Chen, Eva Sapi, David O’malley, Manish Garg, Thomas Rutherford
Journal: Cancer Research (2004)

4885  Introduction: It is well established that anticancer agents induce apoptosis and the disruption of the apoptotic signal may promote treatment resistance. Although several pathways have been proposed to explain chemoresistance, all lead to some specific defect in the mechanism of cellular death. Therefore, modulation of apoptosis by chemosensitizers represents a potential approach for the treatment of chemoresistant tumors. Recently, we showed that Phenoxodiol, a synthetic isoflavone derivative, modulates caspase activation in ovarian cancer cells. The objective of this study was to characterize the molecular mechanism of the drug-resistance to taxotere in ovarian cancer cells and evaluate the effect of phenoxodiol as a chemosensitizer. Materials: Twelve epithelial ovarian cancer cells (EOC) isolated from malignant ovarian ascites were tested for their response to taxotere. Cell viability was determined by the CellTiter 96 assay, apoptosis was assessed by Hoechst stain ing and caspase-3 activity. The presence and activation of caspases and intracellular downstream inhibitors for apoptosis was determined by Western blot analysis. Results: Seven of twelve studied EOC cells responded to taxotere as demonstrated by a decrease in cell viability, chromatin condensation, and caspases activation. In contrast, chemo-resistant EOC cells showed no caspases activation. X-linked inhibitor of apoptosis (XIAP) was expressed in all ovarian cancer cells but it was only inactivated on chemo-sensitive cells. Phenoxodiol treatment of chemo-resistant cells restored taxotere-sensitivity and decreased taxotere LD50 by over 100-fold. Conclusion: Our results indicate 1) taxotere cytotoxic effect is caspase dependent; 2) caspase activation relies on the removal of XIAP; and 3) phenoxodiol restores chemo-sensitivity in taxotere-resistant cancer cells. The significant reduction of taxotere LC50 after phenoxodiol treatment indicates that use of phenoxodiol as a chemosensitizer, in combination with cytotoxic drugs could be more effective for the treatment of refractory ovarian cancer.
Recurrent food impactions
Authors: Florian Hentschel, Andreas Georg Schreyer, Stefan Lüth
Journal: Gut (2020)

Within 4 years, a 58 (to 62)-year-old man attended the emergency department five times because of acute oesophageal food impaction. Other diagnoses included alcohol and tobacco abuse, arterial hypertension, and coronary sclerosis with cardiac infarction and coronary bypass.

On each presentation, the patient complained about mild retrosternal pain and an inability to swallow anything including his own saliva. Vital signs were normal, abdominal examination was unremarkable. Routine laboratory parameters were normal. At first presentation, electrocardiography and serum troponin were normal; chest X-ray suggested moderate lung oedema and no signs of aspiration.

Each time, wedged food was removed endoscopically from various locations in the upper, middle and lower oesophagi within hours after admission. One day after the first bolus …
Prostate-Specific Membrane Antigen–Avid Meningioma Detected in 68Ga–Prostate-Specific Membrane Antigen PET/CT
Authors: Nitin Gupta, Ritu Verma, Ethel S. Belho
Journal: Clinical Nuclear Medicine (2020)

Abstract A 64-year-old man with recently diagnosed prostate adenocarcinoma with a total prostate-specific antigen level of 3.32 ng/mL and Gleason score 4 (3 + 4) was referred for 68 Ga–prostate-specific membrane antigen PET/CT scan for pretreatment staging. Prostate-specific membrane antigen–avid lesion was noted in the right lobe of the prostate gland, corresponding to the known primary lesion. Note was made of another prostate-specific membrane antigen–avid lesion in the right parietal lobe of brain, likely meningioma. MRI scan performed later confirmed the brain lesion to be meningioma.
Glucocorticoid-induced relapse of COVID-19 in a patient with sarcoidosis
Authors: Andrea Hermina Györfi, Markus Kopp, Matthias May, Marcel Vetter, Michael Uder, Andreas E Kremer, Georg Schett, Thomas Harrer, Jörg H W Distler
Journal: Annals of the Rheumatic Diseases (2020)

The COVID-19 pandemic represents a challenge for rheumatologists: how activity of rheumatological diseases or disease-modifying therapies may affect the outcome of SARS-CoV-2 infection is only beginning to be understood. Gianfrancesco et al provided important insights in this regard by evaluating the hospitalisation rate of 600 patients with rheumatological diseases from 40 different countries.1 They found that glucocorticoid treatment in doses equivalent with prednisolone 10 mg/day or higher was associated with an increased hospitalisation rate.

Here, we describe the case of a 50-year-old man who was diagnosed with Lofgren syndrome in January 2019 presenting with cough, bilateral ankle joint swelling and mediastinal lymphadenopathy. ACE (37.3 U/L, normal range <21.4) and soluble IL-2 receptor (1445 U/mL, normal range <710) were elevated in the serum. The patient was treated with glucocorticoids until October 2019 with complete remission of clinical symptoms and normalisation of laboratory parameters.

On 12 March 2020, the patient had contact with a person who later tested positive for SARS-CoV-2 RNA. One week after the SARS-CoV-2 contact, the patient developed fever (38°C) and dry cough suggesting SARS-CoV-2 infection. In addition, he developed pain in the ankles during night …
Erratum to ‘Ten-year Mortality, Disease Progression, and Treatment-related Side Effects in Men with Localised Prostate Cancer from the ProtecT Randomised Controlled Trial According to Treatment Received’ [European Urology 77 (2020) 320–330]
Authors: David E. Neal, Chris Metcalfe, Jenny L. Donovan, J. Athene Lane, Michael Davis, Grace J. Young, Susan J. Dutton, Eleanor I. Walsh, Richard M. Martin, Tim. J. Peters, Emma L. Turner, Malcolm Mason, Richard Bryant, Prasad Bollina, James Catto, Alan Doherty, David Gillatt, Vincent Gnanapragasam, Peter Holding, Owen Hughes, Roger Kockelbergh, Howard Kynaston, Jon Oxley, Alan Paul, Edgar Paez, Derek J. Rosario, Edward Rowe, John Staffurth, Doug G. Altman, Freddie C. Hamdy
Journal: European Urology (2020)
Should Neurologists Be Concerned With REM Sleep Quantity?
Authors: Michael S. Jaffee, Liza H. Ashbrook, Milena K. Pavlova
Journal: JAMA Neurology (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 Neurology 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 Neurology journal
Protein signal pathway mapping: Screening potential drug targets for Multiple Myeloma
Authors: VanMeter Amy, Rosa Gallagher, Valerie Calvert, Jianghong Deng, Michele Signore, Julia Wulfkuhle, Vineela Ayyagari, Christopher Walker, Mariaelena Pierobon, Virginia Espina, Emanuel Petricoin, Lance Liotta
Journal: Cancer Research (2008)

1542  There is an urgent need for novel individualized targeted therapies for Multiple Myeloma. We employed reverse phase protein array (RPPA) technology, to map the activated state of cellular signal pathways following cell culture and ex vivo treatment of myeloma cells, before and after administration of signal pathway inhibitors. We are gathering data to generate a functional MM classifier based on drug target activation and provide a means of testing the hypothesis that cell signaling activation portraits can predict a priori which targeted therapies will most likely cause cell death and apoptosis. We identified major classes of signal pathways that were activated in a population of 195 multiple myeloma bone marrow aspirate samples. We selected pharmacologic pathway inhibitors acting within these pathway classes. Pathway inhibitors found to induce cell death in vitro within 3 days activated the apoptosis pathway within 4 hours of administration.  Three multiple myeloma cell lines were selected for inhibitor studies. NCI-H929 cells secrete large amounts of IgA kappa, whereas RPMI-8226 and U266 cells produce IgG lambda and IgE lambda respectively. Cells were treated at recommended IC50 concentrations with inhibitors targeted against IGF1R, EGFR, AKT, COX2, MEK, AMPK, ERK, BCL-2, and mTOR. Cells were treated with DMSO as the vehicle control. To measure cell viability over time, a trypan blue assay was performed. Proteins were extracted at 0 min, 4 hours, 24 hours, and 48 hours post treatment. Protein lysates were printed onto RPPAs and subsequently immunostained with antibodies to 111 different phosphorylated, cleaved, or total protein cell signaling proteins. Spot analysis software was used to generate spot intensities, with local area background correction. Net spot intensities were normalized to total protein per spot and mean spot intensity values were obtained.  Based on viability data, inhibitor treated cells were categorized into two groups, viable and non-viable. Cells were determined to be viable if
Hirji S Adenwalla
Authors: Sherna F Adenwalla, Alistair R M Cobb
Journal: BMJ (2020)

Hirji S Adenwalla was the world’s longest serving cleft lip and palate surgeon. He worked at the Charles Pinto Centre for Cleft and Craniofacial Anomalies, which he founded at the Jubilee Mission Medical Hospital, Thrissur, Kerala, India. Adenwalla was renowned as a humble, open, and compassionate gentleman, but an exacting, reflective surgeon and a pioneer in his field. He is regarded as the father of modern cleft surgery in India. He was visited by and trained surgeons from India and across the globe, including many of the European, UK, and US plastic, maxillofacial, and cleft surgeons. He remained a mentor to many.

Adenwalla was born in Ahmednagar, Maharashtra, to a Parsi family. After qualifying in medicine, he completed further training at the King Edward Memorial hospital and Jerbai Wadia Hospital, Mumbai, where his father was the dean. It was here that he developed a passion for cleft lip and palate surgery. He also became a proficient anaesthetist, which would stand him in good stead for his early years in Thrissur. He was influenced by the lives of Paul Brand and Ida Scudder and planned to work as a missionary doctor in Africa, when he fell in love with and married Gulnar. Instead, he joined the small Jubilee Mission Hospital in Thrissur in 1959. The 20 bed hospital was basic, and he was one of very few doctors …
Alcohol: WHO tells Europe to raise prices to reduce harm
Authors: Bryan Christie
Journal: BMJ (2020)

Higher alcohol taxes, applied more effectively, are needed throughout Europe to reduce harms from problem drinking in a region with the world’s highest alcohol consumption, says the World Health Organization.

A report produced by its regional office for Europe found overwhelming evidence that raising prices was one of the most cost effective ways to reduce alcohol consumption. Although all European countries impose some form of price regulation, they vary enormously in how alcohol taxes are set and in their effectiveness.

Alcohol Pricing in the WHO European Region 1 summarises the evidence on pricing strategies in reducing harm from alcohol …
Optic Pathways Enlargement on Magnetic Resonance Imaging in Patients with Morning Glory Disc Anomaly
Authors: Guillaume Poillon, Adrien Henry, Olivier Bergès, Franck Bourdeaut, Kamal Chouklati, Grégory Kuchcinski, Georges Caputo, Augustin Lecler, Claire Boutet, Hervé Brisse, Nathalie Cassoux, Emmanuel Cheuret, Sabine Derrien, Monique Elmaleh, Nadine Girard, Jean-François Hak, Clémence Le Pape, Yvonne Purcell, Annick Sevely
Journal: Ophthalmology (2020)
Rapid onset honeycombing fibrosis in spontaneously breathing patient with COVID-19
Authors: Margot Combet, Arthur Pavot, Laurent Savale, Marc Humbert, Xavier Monnet
Journal: European Respiratory Journal (2020)

A 38-year-old man presented with a 6-day history of gradually worsening cough and asthenia and secondary anosmia and agueusia. He had no prior personal medical history. His mother had a history of diabetes mellitus and his son was followed for haemophilia A. His spouse had exhibited similar symptoms a week earlier. Patients with COVID-19 should be monitored for rapid onset honeycombing fibrosis <https://bit.ly/2B7fRcA>
Chitosan/γ-PGA nanoparticles-based immunotherapy as adjuvant to radiotherapy in breast cancer
Authors: Flávia Castro, Marta L. Pinto, Catarina L. Pereira, Karine Serre, Mário A. Barbosa, Karim Vermaelen, Fátima Gärtner, Raquel M. Gonçalves, Olivier De Wever, Maria J. Oliveira
Journal: Biomaterials (2020)
Reasons to be cheerful: the other global crisis
Authors: Helen M Roberts, Roz Shafran
Journal: BMJ (2020)

Nelson is right.1 Covid-19 isn’t the only global emergency. We still have a chance, just, to act on the other emergency—climate—to reduce inequalities and save lives. Holgate reminds us that the air we breathe carries danger as well as life.2 After the dangers of air pollution in London were recognised in the 1950s, the clean air acts that followed reduced fossil fuel emissions with dramatic effect.

If turning to the other emergency while preoccupied with covid-19 feels …
SAT0040 RISK FACTORS FOR DEVELOPING AND MORTALITY FOR ACUTE EXACERBATION OF RHEUMATOID ARTHRITIS-ASSOCIATED INTERSTITIAL LUNG DISEASE
Authors: S. Izuka, H. Yamashita, Y. Takahashi, H. Kaneko
Journal: Annals of the Rheumatic Diseases (2020)

Background: Among collagen vascular diseases, rheumatoid arthritis-associated interstitial lung disease (RA-ILD) is the most commonly associated with ILD with acute exacerbation (AE) [1]. One study reported that ILD diagnosis at an older age, the usual interstitial pneumonia (UIP) pattern on high-resolution computed tomography, and methotrexate (MTX) use were associated with AE in patients with RA-ILD [2]. However, because these studies included few patients, the risk factors and prognosis of AE in patients with RA-ILD remain unclear. Therefore, this study examined the characteristics of RA-ILD patients with AE, and the variables associated with mortality due to AE of RA-ILD. Objectives: To investigate the risk factors for AE and mortality of RA-ILD. Methods: We retrospectively collected the clinical data of 165 RA-ILD patients admitted to our hospital between July 2010 and October 2019. We compared clinical characteristics between patients who developed AE (AE group) and those who did not (non-AE group), and identified the variables significantly associated with AE occurrence. We also compared the admission characteristics of those who survived (survivor group) and those who died (non-survivor group) after admission for AE. AE was defined using previously proposed criteria [3], which were modified slightly for application to RA-ILD. Results: The mean patient age was 73.6 ± 9.7 years and 97 (71.9%) patients were female. Thirty (22.2%) patients developed AE, of whom thirteen (43.3%) died (mean follow-up, 64.9 months). In univariate analyses UIP pattern and MTX were not associated with AE. However, in multivariate analyses, UIP pattern was associated with AE (OR 2.68, 95% CI 1.10–6.52, p =0.03). Median age (70 vs . 80 years, p =0.003), non-use of MTX (70.6% vs . 23.1%, p =0.025), and C reactive protein level (median 9.38 vs . 18.12 mg/dL, p =0.02) on admission were significantly higher in patients who died of AE. In the Cox proportional hazard model, UIP pattern (HR 4.67, 95% CI 1.02–21.5, p =0.048) and non-use of MTX (HR 0.16, 95% CI 0.04–0.72, p =0.016) were associated with death. Conclusion: Our data suggest that the UIP pattern is related to AE, and non-use of MTX and UIP pattern are related to death due to AE of RA-ILD. References: [1] Suda T, Kaida Y, Nakamura Y et al. Acute exacerbation of interstitial pneumonia associated with collagen vascular diseases. Respir Med 2009;103:846-53. [2] Hozumi H, Nakamura Y, Johkoh T et al. Acute exacerbation in rheumatoid arthritis-associated interstitial lung disease: a retrospective case control study. BMJ Open 2013;3:e003132. [3] Collard HR, Moore BB, Flaherty KR et al. Idiopathic pulmonary fibrosis clinical research network investigators. Acute exacerbations of idiopathic pulmonary fibrosis. Am J Respir Crit Care Med 2007;176:636-43. Disclosure of Interests: None declared