tbuckley/cabot-search huggingface dataset:
Correspondence on ‘Long-term efficacy and safety of canakinumab in patients with colchicine-resistant familial Mediterranean fever: results from the randomised phase III CLUSTER trial’
Authors: Hasan Satış, Ergin Aydemir, Kerem İzmirlioğlu, Abdurrahman Tufan
Journal: Annals of the Rheumatic Diseases (2020)

Correspondence on 'Long-term efficacy and safety of canakinumab in patients with colchicine-resistant familial Mediterranean fever: results from the randomised phase III CLUSTER trial'We read with great interest the article "Long-term efficacy and safety of canakinumab in patients with colchicine-resistant familial Mediterranean fever: results from the randomised phase III CLUSTER trial" by Özen et al. 1 This article makes a remarkable contribution to treatment in patients with colchicineresistant familial Mediterranean fever (FMF), which shows a great remission rate with minimal side effects.However, there are some aspects that need to be clarified and discussed.First, it would be better to report the dominant attack-type of the patients because we think musculoskeletal type attacks, especially mild ones, could be skipped and not remembered by the patients when they are admitted to outpatient control.These attacks are also associated with increased damage. 2 Second, there is an inconsistency regarding patient number in canakinumab dosage group between figure 1 and text in the results section.It was written as "44 patients received <2700 mg canakinumab and 16 received ≥2700 mg".However, in the figure, it was stated as 42 and 15, respectively.Baseline median C reactive protein (CRP) levels were higher than normal, and we wonder whether the increased CRP levels are persistent.It was shown that persistent inflammation was related to the increased risk of amyloidosis, kidney dysfunction and proteinuria, 3 but the latter was not discussed in the manuscript.We would like to also know the effect of canakinumab on the proteinuria of those patients.We appreciate the work of Özen et al to highlight the treatment of patients with colchicine-resistant FMF.We believe that this comprehensive study will help the clinician to manage these high-risk group of patients.
Brain immune cells undergo cGAS/STING-dependent apoptosis during herpes simplex virus type 1 infection to limit type I IFN production
Authors: Line S. Reinert, Ahmad S. Rashidi, Diana N. Tran, Georgios Katzilieris-Petras, Astrid K. Hvidt, Mette Gohr, Stefanie Fruhwürth, Chiranjeevi Bodda, Martin K. Thomsen, Mikkel H. Vendelbo, Ahmad R. Khan, Brian Hansen, Petra Bergström, Lotta Agholme, Trine H. Mogensen, Maria H. Christensen, Jens R. Nyengaard, Ganes C. Sen, Henrik Zetterberg, Georges MGM Verjans, Søren R. Paludan
Journal: Journal of Clinical Investigation (2020)

Protection of the brain from viral infections involves the type I IFN (IFN-I) system, defects in which render humans susceptible to herpes simplex encephalitis (HSE). However, excessive cerebral IFN-I levels lead to pathologies, suggesting the need for tight regulation of responses. Based on data from mouse models, human HSE cases, and primary cell culture systems, we showed that microglia and other immune cells undergo apoptosis in the HSV-1–infected brain through a mechanism dependent on the cyclic GMP-AMP synthase/stimulator of interferon genes (cGAS/STING) pathway, but independent of IFN-I. HSV-1 infection of microglia induced cGAS-dependent apoptosis at high viral doses, whereas lower viral doses led to IFN-I responses. Importantly, inhibition of caspase activity prevented microglial cell death and augmented IFN-I responses. Accordingly, HSV-1–infected organotypic brain slices or mice treated with a caspase inhibitor exhibited lower viral load and an improved infection outcome. Collectively, we identify an activation-induced apoptosis program in brain immune cells that downmodulates local immune responses.
Thrombopoietin receptor agonists as an emergency treatment for severe newly diagnosed immune thrombocytopenia in children
Authors: Marie Nolla, Nathalie Aladjidi, Thierry Leblanc, Helder Fernandes, Stéphane Ducassou, Mony Fahd, Vincent Barlogis, Marc Michel, Pascale Blouin, Eric Jeziorski, Joy Benadiba, Corinne Pondarre, Guy Leverger, Marlene Pasquet
Journal: Blood (2020)
SAT0204 Investigation of fluoroquinolone-induced myalgia using 31p magnetic resonance spectroscopy and<i>in vitro</i>contracture tests
Authors: S Guis, D Bendahan, G Kozak-Ribbens, JP Mattei, Y Le Fur, D Figarella-Branger, J Jouglard, PJ Cozzone
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Adverse rheumatological effects of fluoroquinolone treatment such as tendinopathies, arthralgia and myalgia have been reported. The exact mechanism of fluoroquinolone toxicity remains unclear. <h3>Objectives</h3> To investigate muscle function in patients suffering from severe myalgia resulting from fluoroquinolone treatment. We used histology, <i>in vitro</i> contracture tests (IVCT) and 31P magnetic resonance spectroscopy (31P MRS) to explore muscular contraction and metabolism. <h3>Methods</h3> Three patients were investigated suffering after fluoroquinolone treatment from myalgia, hyperalgia tendinopathy and arthralgia. Control group included nine subjects, all of them were free of any muscle disease. Muscle biopsies were performed on the left biceps, IVCT were performed in accordance with the protocol recommended by European Malignant Hyperpyrexia Group (EMHG). 31P MRS concicted to MR spectra of forearm flexor muscles were recorded at 4.7 T throughout a rest-exercise-recovery protocol. <h3>Results</h3> No specific histologic anomalies were observed in muscle biopsies. <i>In vitro</i> contracture tests diagnosed one patient as susceptible to Malignant hyperthermia. 31P MRS detected in all patients a significant reduction of pH magnitude changes measured at end of exercise and a faster rate of proton efflux measured during recovery. <h3>Conclusion</h3> Muscle abnormalities described in the present study of three patients after fluoroquinolone treatment clearly pointed out the organicity of fluoroquinolone-induced myalgia. All three patients displayed an aceleration of proton efflux and a limited acidosis likely in relation with changes of transporters involving in the transport of Na+, H+ and Ca<sup>2+</sup>.
Engineered Full‐Length Fibronectin–Hyaluronic Acid Hydrogels for Stem Cell Engineering
Authors: Sara Trujillo, Sebastián L. Vega, Kwang Hoon Song, Ana San Félix, Matthew J. Dalby, Jason A. Burdick, Manuel Salmeron‐Sanchez
Journal: Advanced Healthcare Materials (2020)

Abstract Mechanical cues induce a variety of downstream effects on cells, including the regulation of stem cell behavior. Cell fate is typically characterized on biomaterial substrates where mechanical and chemical properties can be precisely tuned; however, most of these substrates do not recapitulate the biological complexity of the extracellular matrix (ECM). Here, hydrogels are engineered for mechanobiological studies using two major components of the ECM: hyaluronic acid (HA) and fibronectin (FN). Rather than typical surface chemisorption of FN to substrates, the system contains full‐length FN covalently crosslinked to HA throughout the hydrogel. The control over the mechanical properties of the hydrogel independent of the concentration of FN and the ability to culture viable cells either on top or encapsulated within the hydrogels are shown. Interestingly, human mesenchymal stem cells (MSCs) experience an increase in nuclear translocation of the yes‐associated protein (YAP) to the nucleus when cultured on (2D) substrates with increasing amounts of FN while maintaining constant hydrogel stiffness. However, this FN dependence on nuclear YAP translocation is not observed for MSCs encapsulated in (3D) hydrogels. This work develops complex hydrogels that recapitulate features of the ECM for the control of stem cells in both 2D and 3D environments.
Single-session endoscopic ultrasound-guided gallbladder drainage combined with ERCP for acute cholecystitis and choledocholithiasis in a nonsurgical patient
Authors: Mariano Villarroel, Carlos de la Serna-Higuera, Manuel Pérez-Miranda
Journal: Endoscopy (2020)

A 93-year-old man with a recent history of acute coronary syndrome presented with upper right abdominal pain and jaundice. Laboratory analysis showed leukocytosis, elevated C-reactive protein, hypertransaminasemia, and cholestasis (total bilirubin 4.39 mg/dL, alkaline phosphatase 137 U/L, and γ-glutamyltransferase 287 U/L). Abdominal ultrasonography revealed acute cholecystitis with a dilated common bile duct.
Abstract A01: Clinical detection of melanoma via endogenous fluorophore lifetime imaging
Authors: Peter A. Pellionisz, Yong Hu, Jenny Kim, Warren Grundfest, Maie A. St. John
Journal: Cancer Research (2020)

Abstract Objective: The 5-year survival for cutaneous malignant head and neck melanoma is very poor (17%). As proof of principle, we detect variations in endogenous fluorophore lifetimes by illuminating tissue with pulsed ultraviolet (UV) light. We have previously shown that dynamic optical contrast imaging is capable of delineating tumor margins. Our aim herein was to acquire clinical and intraoperative multispectral images that permit selection of regions of interest (ROI) to reliably and noninvasively perform a rapid optical biopsy in the patient. Methods: Patient cases of cutaneous melanoma were acquired with pulsed UV illumination utilizing a 6-diode in-series system. Emitted fluorescence was detected with a nanosecond gated CCD detector. The acquired signal is transformed into a relative difference value representing tissue fluorophore lifetime. Results: From (n=4) patient cases we acquired DOCI images both pre- and post-resection leading to a database of in vivo relative lifetime values that align to histology sections from corresponding locations via pathology. The spectral features of our images enabled classification of clinician-determined regions of interest in DOCI images in order to establish measures of internal and external validity of our novel device. Conclusion: Our device augments native tissue contrast via wide-field imaging to produce spatially resolved and pathology-specific maps of tissue. Our database of histology-matched real-time images is aimed to permit intraoperative guidance for tumor margin delineation in dermatologic surgery. Citation Format: Peter A. Pellionisz, Yong Hu, Jenny Kim, Warren Grundfest, Maie A. St. John. Clinical detection of melanoma via endogenous fluorophore lifetime imaging [abstract]. In: Proceedings of the AACR Special Conference on Melanoma: From Biology to Target; 2019 Jan 15-18; Houston, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(19 Suppl):Abstract nr A01.
Progressive Dry Cough in a Patient With ROS1-Rearranged Lung Adenocarcinoma Undergoing Crizotinib Therapy
Authors: Chang-Yao Chu, Hong-Ping Er, Chien-Chung Lin
Journal: JAMA Oncology (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 Oncology 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 Oncology journal
Public health, pandemic response, and the 2020 US election
Authors: Esther K Choo, Aaron E Carroll
Journal: The Lancet Public Health (2020)

COVID-19 pandemic, and both the immediate failures and structural forces that let it play out so disastrously in the USA, or they can accept that we need change and articulate a real plan for it.The USA can achieve global health excellence, but leadership is needed to guide the country away from counterproductive assumptions of US exceptionalism, recognising with humility where we fall short and where we have much to learn from countries that fare better in health outcomes, both before and in COVID times.We need to start rebuilding with a solid framework, one capable of sheltering every American individual's health and one that will stand strong through the next global health crisis.We declare no competing interests.
Covid-19: how to prioritize worse-off populations in allocating safe and effective vaccines
Authors: Harald Schmidt, Parag Pathak, Tayfun Sönmez, M Utku Ünver
Journal: BMJ (2020)

How should we decide which population groups receive covid-19 vaccines before others? <b>Harald Schmidt</b>, <b>Parag Pathak</b>, <b>Tayfun Sönmez</b>, and <b>M Utku Ünver</b> examine the existing frameworks and argue that prioritizing worse-off groups is urgent, justified, and feasible
Implications of Alternative Definitions of Peri-Procedural Myocardial Infarction After Coronary Revascularization
Authors: John Gregson, Gregg W. Stone, Ori Ben-Yehuda, Björn Redfors, David E. Kandzari, Marie-Claude Morice, Martin B. Leon, Ioanna Kosmidou, Nicholas J. Lembo, W. Morris Brown, Dimitri Karmpaliotis, Adrian P. Banning, Jose Pomar, Manel Sabaté, Charles A. Simonton, Ovidiu Dressler, Arie Pieter Kappetein, Joseph F. Sabik, Patrick W. Serruys, Stuart J. Pocock
Journal: Journal of the American College of Cardiology (2020)
Abstract B09: Nitric oxide stimulates PI3K-AKT pathway activation by S-nitrosylation of PTEN in human melanoma cells
Authors: Zhen Ding, Dai Ogata, Jason Roszik, Yong Qin, Sun-Hee Kim, Suhendan Ekmekcioglu, Elizabeth A. Grimm
Journal: Cancer Research (2020)

Abstract Based on our previous finding that inflammation associated nitric oxide synthase (NOS) expression in melanoma and its association with poor prognosis in melanoma patients, we investigated the role of nitric oxide (NO) on the PI3K-Akt pathway. Human melanoma cell lines were exposed in vitro to the NO donor (DETA NONOate), and increased Akt Serine 473 phosphorylation (pAkt S473) was detected after addition of 50-500μM DETA NONOate at as early as 2 hours. Significant increases of pAkt S473 were observed mostly in cell lines with wild-type PTEN, such as A375 and MeWo, which under our conditions do not have elevated basal Akt phosphorylation. A375 cells were further examined for DETA NONOate-induced functional consequences of Akt phosphorylation and activation; enhanced kinase activity was found to increase phosphorylation of 12 of 16 AKT signaling proteins, which include GSK, MAPK, Bad, and others. By analyzing melanoma data in The Cancer Genome Atlas (TCGA), we found a similar result that patients with positive iNOS mRNA expression have higher pAkt S473 levels compared with those without iNOS. When both PTEN and iNOS expression status were analyzed, pAkt S473 is only significantly (P&amp;lt;0.05) increased in patients with positive iNOS and intact PTEN, supporting our hypothesis that NO may inhibit the role of PTEN as the PI3K antagonist. Further examination in A375 cells expressing iNOS confirmed the endogenous formation of PTEN S-nitrosylation (SNO), a NO-dependent post-translational modification. PTEN in cells treated with NO showed attenuated phosphatase activity. Consistent with this view, an analysis from stage III melanoma patient tissue microarray also revealed that patients with PTEN expression had a lower survival rate when they also had positive iNOS expression. In summary, our study revealed NO can stimulate the PI3K-Akt pathway in human melanoma cells, which could be promoted by NO-mediated PTEN SNO. These experimental discoveries are supported by clinical association data and have provided one plausible mechanistic insight into the possible functional consequences of inflammatory NO produced in human melanoma cells and microenvironment. Citation Format: Zhen Ding, Dai Ogata, Jason Roszik, Yong Qin, Sun-Hee Kim, Suhendan Ekmekcioglu, Elizabeth A. Grimm. Nitric oxide stimulates PI3K-AKT pathway activation by S-nitrosylation of PTEN in human melanoma cells [abstract]. In: Proceedings of the AACR Special Conference on Melanoma: From Biology to Target; 2019 Jan 15-18; Houston, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(19 Suppl):Abstract nr B09.
Volume Status Impacts CMR–Extracellular Volume Measurements and Outcome in AS Undergoing TAVR
Authors: Christian Nitsche, Andreas A. Kammerlander, Matthias Koschutnik, Carolina Donà, Stefan Aschauer, Leah Sinnhuber, Anna Eidenberger, Nabila Forutan, Florian Schartmueller, Martin Andreas, Dietrich Beitzke, Jutta Bergler-Klein, Philipp E. Bartko, Jolanta Siller-Matula, Max-Paul Winter, Anahit Anvari-Pirsch, Georg Goliasch, Christian Hengstenberg, Julia Mascherbauer
Journal: JACC. Cardiovascular imaging (2020)
Read, Write, Adapt: Challenges and Opportunities during Kinetoplastid Genome Replication
Authors: Jeziel D. Damasceno, Catarina A. Marques, Jennifer Black, Emma Briggs, Richard McCulloch
Journal: Trends in Genetics (2020)

The genomes of all organisms are read throughout their growth and development, generating new copies during cell division and encoding the cellular activities dictated by the genome's content. However, genomes are not invariant information stores but are purposefully altered in minor and major ways, adapting cellular behaviour and driving evolution. Kinetoplastids are eukaryotic microbes that display a wide range of such read-write genome activities, in many cases affecting critical aspects of their biology, such as host adaptation. Here we discuss the range of read-write genome changes found in two well-studied kinetoplastid parasites, Trypanosoma brucei and Leishmania, focusing on recent work that suggests such adaptive genome variation is linked to novel strategies the parasites use to replicate their unconventional genomes.
MAL2 drives immune evasion in breast cancer by suppressing tumor antigen presentation
Authors: Yuanzhang Fang, Lifei Wang, Changlin Wan, Yifan Sun, Kevin Van der Jeught, Zhuolong Zhou, Tianhan Dong, Ka Man So, Tao Yu, Yujing Li, Haniyeh Eyvani, Austyn B. Colter, Edward Dong, Sha Cao, Jin Wang, Bryan P. Schneider, George E. Sandusky, Yunlong Liu, Chi Zhang, Xiongbin Lu, Xinna Zhang
Journal: Journal of Clinical Investigation (2020)

Immune evasion is a pivotal event in tumor progression. To eliminate human cancer cells, current immune checkpoint therapy is set to boost CD8+ T cell–mediated cytotoxicity. However, this action is eventually dependent on the efficient recognition of tumor-specific antigens via T cell receptors. One primary mechanism by which tumor cells evade immune surveillance is to downregulate their antigen presentation. Little progress has been made toward harnessing potential therapeutic targets for enhancing antigen presentation on the tumor cell. Here, we identified MAL2 as a key player that determines the turnover of the antigen-loaded MHC-I complex and reduces the antigen presentation on tumor cells. MAL2 promotes the endocytosis of tumor antigens via direct interaction with the MHC-I complex and endosome-associated RAB proteins. In preclinical models, depletion of MAL2 in breast tumor cells profoundly enhanced the cytotoxicity of tumor-infiltrating CD8+ T cells and suppressed breast tumor growth, suggesting that MAL2 is a potential therapeutic target for breast cancer immunotherapy.
New hospitals: Funding pledge falls short of what’s needed, say experts
Authors: Gareth Iacobucci
Journal: BMJ (2020)

The government’s plan to build or refurbish 40 hospitals in England will fall short of what is required without substantial extra investment, healthcare leaders have warned.

On 30 September the prime minister announced a £3.7bn (€4.1bn; $4.8bn) allocation for 40 hospitals to be built by 2030, under the government’s health infrastructure plan.1

But only £1.6bn of this is new money. The remainder has already been announced by ministers, including £850m last year to upgrade outdated facilities and equipment at 20 hospitals.

The money will fund six hospital building projects being undertaken between now and 2025 and a further 21 schemes …
Competitive sport, therapy, and physical education: voices of young people with cerebral palsy who have high support needs
Authors: Eimear Enright, Emma M Beckman, Mark J Connick, Iain Mayank Dutia, Angelo Macaro, Paula J Wilson, Jennifer O'Sullivan, Jean-Michel Lavalliere, Turner Block, Leanne M Johnston, Gaj Panagoda, Sean M Tweedy
Journal: British Journal of Sports Medicine (2020)

People with cerebral palsy (CP) participate in significantly less physical activity than the general population and those with more severe CP and higher support needs are the most inactive.1 Anecdotally, generations of para athletes have reported that physically demanding, competitive sport enhances their general health, improves clinical outcomes and that the sports context is meaningful, enjoyable and socially engaging.2 However these views - particularly those of Para athletes with severe impairments and high support needs - are largely absent from the scientific record.3

Here are the voices of three (2M, 1F) early-career athletes with severe CP and high support needs (class IV, Gross Motor Function Classification System). Each completed 3 years in ParaSTART, a performance-focused swimming training programme. The full protocol has been published3 and a 3 min video summary is available here—https://youtu.be/P_r12QAOvWE. At enrolment, athletes were: 15–16 years old, attending school, not meeting physical activity guidelines, not previously trained for any sport and medically fit to participate.

A multiprofessional team with skills in swimming coaching, exercise science and physiotherapy developed and delivered the swim programme, supported by a medical doctor, dietician, sports psychologist and personal support workers. A typical in-season training week comprised 3–4x30 min sessions of moderate and vigorous pool and gym-based training, a total training volume of >650 Rating of Perceived Exertion (using OMNI4) minutes.

The stories we share here are based on athlete interviews conducted by an experienced, independent, qualitative researcher, initially using a life history method and, …