tbuckley/cabot-search huggingface dataset:
Glycosphingolipids and neuroinflammation in Parkinson’s disease
Authors: Karim Belarbi, Elodie Cuvelier, Marie-Amandine Bonte, Mazarine Desplanque, Bernard Gressier, David Devos, Marie-Christine Chartier-Harlin
Journal: Molecular Neurodegeneration (2020)

Abstract Parkinson's disease is a progressive neurodegenerative disease characterized by the loss of dopaminergic neurons of the nigrostriatal pathway and the formation of neuronal inclusions known as Lewy bodies. Chronic neuroinflammation, another hallmark of the disease, is thought to play an important role in the neurodegenerative process. Glycosphingolipids are a well-defined subclass of lipids that regulate crucial aspects of the brain function and recently emerged as potent regulators of the inflammatory process. Deregulation in glycosphingolipid metabolism has been reported in Parkinson’s disease. However, the interrelationship between glycosphingolipids and neuroinflammation in Parkinson’s disease is not well known. This review provides a thorough overview of the links between glycosphingolipid metabolism and immune-mediated mechanisms involved in neuroinflammation in Parkinson’s disease. After a brief presentation of the metabolism and function of glycosphingolipids in the brain, it summarizes the evidences supporting that glycosphingolipids (i.e. glucosylceramides or specific gangliosides) are deregulated in Parkinson’s disease. Then, the implications of these deregulations for neuroinflammation, based on data from human inherited lysosomal glycosphingolipid storage disorders and gene-engineered animal studies are outlined. Finally, the key molecular mechanisms by which glycosphingolipids could control neuroinflammation in Parkinson’s disease are highlighted. These include inflammasome activation and secretion of pro-inflammatory cytokines, altered calcium homeostasis, changes in the blood-brain barrier permeability, recruitment of peripheral immune cells or production of autoantibodies.
Memory Care Unit
Authors: Rebekka DePew
Journal: Annals of Internal Medicine (2020)

Ad Libitum20 October 2020Memory Care UnitRebekka DePewRebekka DePewVanderbilt University Medical School, Nashville, Tennessee (R.D.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/M19-2736 Audio Reading - “Memory Care Unit” Audio. Michael A. LaCombe, MD, Annals Associate Editor, reads “Memory Care Unit” by Rebekka DePew Your browser does not support the audio element. Audio player progress bar Step backward in current audio track Play current audio trackPause current audio track Step forward in current audio track Mute current audio trackUnmute current audio track 00:00/ SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail These are the paperglass-thin daysthat we remember. The catlying in the window as she did then.The air that swells with rain. The music.The afternoons pass withoutmuch reluctance. Inside, theair is warm. We sweat when wesleep. We wake up to livesthat belong to selves we donot quite claim.Tell us about the first ones,they will ask. The days when younearly drowned and came uplaughing. We will not remember.Already we have forgotten.They will settle for otherstories. Of these days.These days that happened,and never stopped. Author, Article, and Disclosure InformationAffiliations: Vanderbilt University Medical School, Nashville, Tennessee (R.D.)Current Author Address: Rebekka DePew; e-mail, [email protected]com. PreviousarticleNextarticle Advertisement Audio Reading - “Memory Care Unit” Audio. Michael A. LaCombe, MD, Annals Associate Editor, reads “Memory Care Unit” by Rebekka DePew Your browser does not support the audio element. Audio player progress bar Step backward in current audio track Play current audio trackPause current audio track Step forward in current audio track Mute current audio trackUnmute current audio track 00:00/ FiguresReferencesRelatedDetails Metrics 20 October 2020Volume 173, Issue 8Page: 637KeywordsDeceptionMemorySleepSweat ePublished: 20 October 2020 Issue Published: 20 October 2020 Copyright & PermissionsCopyright © 2020 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Retraction notice to Diagnosis of Microvascular Angina Using Cardiac Magnetic Resonance
Authors: Alexander Liu, Rohan S. Wijesurendra, Joanna M. Liu, John C. Forfar, Keith M. Channon, Michael Jerosch-Herold, Stefan K. Piechnik, Stefan Neubauer, Rajesh K. Kharbanda, Vanessa M. Ferreira
Journal: Journal of the American College of Cardiology (2020)

This article has been retracted: please see Elsevier Policy on Article Withdrawal ( ).

The JACC Journals Ethics Board has voted to retract this paper, relying on the findings of misconduct after an investigation by the
Central Ceramide Signaling Mediates Obesity-Induced Precocious Puberty
Authors: Violeta Heras, Juan Manuel Castellano, Daniela Fernandois, Inmaculada Velasco, Elvira Rodríguez-Vazquez, Juan Roa, Maria Jesus Vazquez, Francisco Ruiz-Pino, Matias Rubio, Rafael Pineda, Encarnacion Torres, Maria Soledad Avendaño, Alfonso Paredes, Leonor Pinilla, Denise Belsham, Carlos Diéguez, Francisco Gaytán, Nuria Casals, Miguel López, Manuel Tena-Sempere
Journal: Cell Metabolism (2020)
Baseline BMI and BMI variation during first line pembrolizumab in NSCLC patients with a PD-L1 expression ≥ 50%: a multicenter study with external validation
Authors: Alessio Cortellini, Biagio Ricciuti, Marcello Tiseo, Emilio Bria, Giuseppe L Banna, Joachim GJV Aerts, Fausto Barbieri, Raffaele Giusti, Diego L Cortinovis, Maria R Migliorino, Annamaria Catino, Francesco Passiglia, Mariangela Torniai, Alessandro Morabito, Carlo Genova, Francesca Mazzoni, Vincenzo Di Noia, Diego Signorelli, Alain Gelibter, Mario Alberto Occhipinti, Francesca Rastelli, Rita Chiari, Danilo Rocco, Alessandro Inno, Michele De Tursi, Pietro Di Marino, Giovanni Mansueto, Federica Zoratto, Francesco Grossi, Marco Filetti, Pamela Pizzutilo, Marco Russano, Fabrizio Citarella, Luca Cantini, Giada Targato, Olga Nigro, Miriam G Ferrara, Sebastiano Buti, Simona Scodes, Lorenza Landi, Giorgia Guaitoli, Luigi Della Gravara, Fabrizio Tabbò, Serena Ricciardi, Alessandro De Toma, Alex Friedlaender, Fausto Petrelli, Alfredo Addeo, Giampiero Porzio, Corrado Ficorella
Journal: Journal for ImmunoTherapy of Cancer (2020)

Background The association between obesity and outcomes in patients receiving programmed death-1/programmed death ligand-1 (PD-L1) checkpoint inhibitors has already been confirmed in pre-treated non-small cell lung cancer (NSCLC) patients, regardless of PD-L1 tumor expression. Methods We present the outcomes analysis according to baseline body mass index (BMI) and BMI variation in a large cohort of metastatic NSCLC patients with a PD-L1 expression ≥50%, receiving first line pembrolizumab. We also evaluated a control cohort of metastatic NSCLC patients treated with first line platinum-based chemotherapy. Normal weight was set as control group. Results 962 patients and 426 patients were included in the pembrolizumab and chemotherapy cohorts, respectively. Obese patients had a significantly higher objective response rate (ORR) (OR=1.61 (95% CI: 1.04–2.50)) in the pembrolizumab cohort, while overweight patients had a significantly lower ORR (OR=0.59 (95% CI: 0.37–0.92)) within the chemotherapy cohort. Obese patients had a significantly longer progression-free survival (PFS) (HR=0.61 (95% CI: 0.45–0.82)) in the pembrolizumab cohort. Conversely, they had a significantly shorter PFS in the chemotherapy cohort (HR=1.27 (95% CI: 1.01–1.60)). Obese patients had a significantly longer overall survival (OS) within the pembrolizumab cohort (HR=0.70 (95% CI: 0.49–0.99)), while no significant differences according to baseline BMI were found in the chemotherapy cohort. BMI variation significantly affected ORR, PFS and OS in both the pembrolizumab and the chemotherapy cohorts. Conclusions Baseline obesity is associated to significantly improved ORR, PFS and OS in metastatic NSCLC patients with a PD-L1 expression of ≥50%, receiving first line pembrolizumab, but not among patients treated with chemotherapy. BMI variation is also significantly related to clinical outcomes.
Nature's marvels endowed in gaseous molecules I: Carbon monoxide and its physiological and therapeutic roles
Authors: Xiaoxiao Yang, Wen Lu, Christopher P. Hopper, Bowen Ke, Binghe Wang
Journal: Acta Pharmaceutica Sinica B (2020)

Nature has endowed gaseous molecules such as O2, CO2, CO, NO, H2S, and N2 with critical and diverse roles in sustaining life, from supplying energy needed to power life and building blocks for life's physical structure to mediating and coordinating cellular functions. In this article, we give a brief introduction of the complex functions of the various gaseous molecules in life and then focus on carbon monoxide as a specific example of an endogenously produced signaling molecule to highlight the importance of this class of molecules. The past twenty years have seen much progress in understanding CO's mechanism(s) of action and pharmacological effects as well as in developing delivery methods for easy administration. One remarkable trait of CO is its pleiotropic effects that have few parallels, except perhaps its sister gaseous signaling molecules such as nitric oxide and hydrogen sulfide. This review will delve into the sophistication of CO-mediated signaling as well as its validated pharmacological functions and possible therapeutic applications.
Metabolism, Oxygen, Ischaemia and ProtectionP558Intrauterine growth restriction is associated with a maturation delay of cardiac energetic microdomains
Authors: A. Gonzalez-Tendero, I. Torre, F. Garcia-Garcia, J. Dopazo, E. Gratacos
Journal: Cardiovascular Research (2012)

PurposeIntrauterine growth restriction (IUGR) affects 7-10% of pregnancies and is associated with cardiovascular remodelling and dysfunction persisting into adulthood, resulting in dilated and less efficient hearts. However, the precise underlying mechanism is poorly understood. Cardiac muscle is th
Warfarin in patients with mechanical heart valves
Authors: Fiona Catterall, Paul RJ Ames, Chris Isles
Journal: BMJ (2020)

### What you need to know

A 55 year old woman with severe aortic stenosis underwent valve replacement with a mechanical valve. She has been started on warfarin and is maintaining an international normalised ratio (INR) within the target range of 2.0-3.0. She finds monitoring INR levels cumbersome. She has heard about newer direct oral anticoagulants and asks if she can switch to one of these. 

Valve replacement or repair is the definitive treatment in those with severe valvular heart disease. The choice of valve depends on valve durability, the need for antithrombotic therapy, and patient preferences.12 Mechanical heart valves are preferred in patients under 65.3 Bioprosthetic valves do not require lifelong anticoagulation but have a greater rate of primary failure and are associated with a higher reoperation rate. They last only 10 to 15 years compared with 20 to 30 years for mechanical heart valves.3

Warfarin is an anticoagulant prescribed to patients with mechanical heart valves. Patients with mechanical heart valves have a risk of thrombosis on the valve and subsequent embolism. Blood flows at high shear stress around the valve, which activates platelets and local coagulation. Latest European, US, and National Institute of Health and Care Excellence (NICE) guidelines recommend lifelong treatment with warfarin to prevent this.1245

Warfarin is a vitamin K antagonist. Other drugs in this group are acenocoumarol and dicoumarol. Warfarin inhibits the synthesis of the vitamin K dependent …
1MO A proteomics-based platform for predicting response to immunotherapy and personalising treatment plans
Authors: Y. Shaked, C. Lahav, M. Harel, E. Jacob, E. Issler, E. Fremder, H. Bar, O. Sharon, I. Kamer, A. Dicker, R. Berger, J. Bar
Journal: Annals of Oncology (2020)
HX008, an anti-PD1 antibody, plus irinotecan as second-line treatment for advanced gastric or gastroesophageal junction cancer: a multicenter, single-arm phase II trial
Authors: Yan Song, Ning Li, Qun Li, Xinjun Liang, Shu Zhang, Qingxia Fan, Xianli Yin, Zhixiang Zhuang, Yunpeng Liu, Jingdong Zhang, Xiaoge Kou, Haijun Zhong, Xiaofei Wang, Yiwei Dou, Jing Huang
Journal: Journal for ImmunoTherapy of Cancer (2020)

Irinotecan is used as second-line treatment in advanced gastric or gastroesophageal junction (G/GEJ) cancer. The role of anti-programmed death-1 (PD-1) antibody plus irinotecan, in this setting and population is unclear.This multicenter, open-label, single-arm, phase II trial was conducted in 11 Chinese hospitals. Eligible patients had histologically confirmed advanced G/GEJ cancer that refractory to, or intolerant of, first-line chemotherapy with a platinum and/or fluoropyrimidine. Subjects received HX008 200 mg intravenously every 3 weeks plus irinotecan 160 mg/m2 intravenously every 2 weeks until disease progression or unacceptable toxicity. The primary end point was objective response rate (ORR) as assessed according to Response Evaluation Criteria In Solid Tumors V.1.1.Between October 2018 and September 2019, a total of 58 patients with advanced G/GEJ cancer were enrolled in this study. Median follow-up was 10.5 months (range 7.4-18.9) months. Confirmed ORR was observed in 16 patients, for an ORR of 27.6% (95% CI 16.1% to 39.1%); 19 patients experienced stable disease, leading to a disease control rate of 60.3% (95% CI 46.4% to 73.0%). ORR in patients with PD-ligand 1 (L1) positive (Combined Positive Score (CPS) ≥1) and negative (CPS＜1) tumors was 38.5% (5/13) and 37.5% (3/8), respectively. Median duration of response was 8.0 months (range 1.5-12.5), 6 of 16 (37.5%) responses were ongoing. Median progression-free survival (PFS) was 4.2 months (95% CI 2.2 to 5.5). Median overall survival (OS) was not reached (NR) (95% CI 8.7 to NR). Patients with PD-L1 positive tumors tended to have longer OS than those with PD-L1 negative tumors, but the difference was not statistically significant (NR vs 8.7 months, p=0.1858).The most common treatment-related adverse events of grade 3 or 4 included neutropenia (32.8%), leukopenia (31.0%), anemia (17.2%), decreased appetite (8.6%), vomit (6.9%), nausea (6.9%) and fatigue (5.2%). There were no treatment-related deaths.The combination of HX008 and irinotecan demonstrated promising activity and manageable safety as second-line treatment in patients with advanced G/GEJ cancer, which warrants further study.NCT03704246.
Cancer Plasticity: The Role of mRNA Translation
Authors: Laura J. Lee, David Papadopoli, Michael Jewer, Sonia del Rincon, Ivan Topisirovic, Mitchell G. Lawrence, Lynne-Marie Postovit
Journal: Trends in cancer (2020)

Neoplastic progression is characterized by alterations in tissue architecture, such as a loss of structure–function relationships and the emergence of dedifferentiated histopathologies.To progress, metastasize, and evade therapies, cancer cells must adapt to new and unfavorable microenvironments.Cancer cell plasticity occurs concomitantly with tumor progression and can limit the effectiveness of anticancer therapies.Protein synthesis is often dysregulated in neoplasia, with translational reprogramming emerging as a central feature of adaptive plasticity.Dissecting the mechanisms of translational reprograming in response to changing tumor microenvironments holds a promise to clarify the molecular underpinnings of cancer cell plasticity and its corresponding histopathological manifestations. Tumor progression is associated with dedifferentiated histopathologies concomitant with cancer cell survival within a changing, and often hostile, tumor microenvironment. These processes are enabled by cellular plasticity, whereby intracellular cues and extracellular signals are integrated to enable rapid shifts in cancer cell phenotypes. Cancer cell plasticity, at least in part, fuels tumor heterogeneity and facilitates metastasis and drug resistance. Protein synthesis is frequently dysregulated in cancer, and emerging data suggest that translational reprograming collaborates with epigenetic and metabolic programs to effectuate phenotypic plasticity of neoplasia. Herein, we discuss the potential role of mRNA translation in cancer cell plasticity, highlight emerging histopathological correlates, and deliberate on how this is related to efforts to improve understanding of the complex tumor ecology. Tumor progression is associated with dedifferentiated histopathologies concomitant with cancer cell survival within a changing, and often hostile, tumor microenvironment. These processes are enabled by cellular plasticity, whereby intracellular cues and extracellular signals are integrated to enable rapid shifts in cancer cell phenotypes. Cancer cell plasticity, at least in part, fuels tumor heterogeneity and facilitates metastasis and drug resistance. Protein synthesis is frequently dysregulated in cancer, and emerging data suggest that translational reprograming collaborates with epigenetic and metabolic programs to effectuate phenotypic plasticity of neoplasia. Herein, we discuss the potential role of mRNA translation in cancer cell plasticity, highlight emerging histopathological correlates, and deliberate on how this is related to efforts to improve understanding of the complex tumor ecology.
Epidemiology of adrenal tumours in Olmsted County, Minnesota, USA: a population-based cohort study
Authors: Andreas Ebbehoj, Dingfeng Li, Ravinder J Kaur, Catherine Zhang, Sumitabh Singh, Taoran Li, Elizabeth Atkinson, Sara Achenbach, Sundeep Khosla, Wiebke Arlt, William F Young, Walter A Rocca, Irina Bancos
Journal: The Lancet Diabetes & Endocrinology (2020)
Patient age and risk of recurrence of primary melanoma at high risk of spread
Authors: R. Ghiasvand, K. Khosrotehrani, M.C.B. Hughes, L.A. Schuckmann, V.L. Beesley, M. Malt, B.M. Smithers, A.C. Green
Journal: British Journal of Dermatology (2020)

Melanoma is more aggressive with poorer outcomes in older than younger patients. Older age has been associated with greater tumour thickness, higher rates of ulceration, and high mitotic rates, but it is not clear whether poorer outcomes in the elderly are solely due to these tumour-specific features or to additional effects of age-related decline in in immune surveillance, greater comorbidity, and age-related behaviours such as delayed diagnosis.
Recurrent Brain Metastasis of Triple Negative Breast Cancer With High Uptake in 68Ga-PSMA-11 PET/CT
Authors: Esra Arslan, Nurhan Ergül, Yeşim Karagöz, Arzu Algün Gedik, Tevfik Fikret Çermik
Journal: Clinical Nuclear Medicine (2020)

Abstract Triple negative breast cancer (TNBC) is characterized by poor prognosis and limited response to standard treatments. Although 18 F-FDG PET/CT is frequently used in staging and restaging, in some cases, it may be insufficient considering tumor heterogeneity. Prostate-specific membrane antigen (PSMA) has been reported to be overexpressed in many types of cancer due to tumor-associated neovascularization. 68 Ga-PSMA-11 PET/CT can be used to demonstrate radionuclide therapy option as well as detection of primary tumor and recurrence in TNBC. We present a 47-year-old woman with TNBC having recurrent brain metastasis with avid PSMA receptor activity versus low FDG uptake.
Unintended and teen pregnancy experiences of trans masculine people living in the United States
Authors: Brittany M. Charlton, Colleen A. Reynolds, Ariella R. Tabaac, Eli G. Godwin, Lauren M. Porsch, Madina Agénor, Frances W. Grimstad, Sabra L. Katz-Wise
Journal: International Journal of Transgender Health (2020)

Trans masculine people are more likely than cisgender peers to have a teen or unintended pregnancy, though little is known about the origins of these disparities.This study aimed to describe teen and unintended pregnancy experiences among trans masculine people in order to elucidate risk factors and pregnancy-related needs.As a part of the United States-based SexuaL Orientation, Gender Identity, and Pregnancy Experiences (SLOPE) study, in-depth, semi-structured interviews were conducted between March 2017 and August 2018 with 10 trans masculine people, ages 20-59 years, who experienced a teen or unintended pregnancy. Audio-recorded interviews were professionally transcribed, then analyzed using immersion/crystallization and thematic analysis approaches. The themes were contextualized using sociodemographic survey data.The four themes that were developed from participants' narratives highlighted: 1) how trans masculine people navigated having a pregnant body (e.g., heightened gender dysphoria due to being pregnant); 2) the importance of the cultural environment in shaping experiences as a trans masculine pregnant person (e.g., pregnancy and gender-related job discrimination); 3) the development of the pregnancy over time (e.g., decision-making processes); and 4) how pregnancy (and gender identity) affected relationships with other people (e.g., adverse family of origin experiences).This study identified a number of risk factors for teen and unintended pregnancies among trans masculine people including physical and sexual abuse as well as ineffective use of contraception. This research also identifies unique needs of this population, including: relieving gender dysphoria, combating discrimination, and ensuring people feel visible and welcome, particularly in reproductive healthcare spaces. Public health practitioners, healthcare providers, and support networks (e.g., chosen family) can be key sources of support. Attention to risk factors, unique needs, and sources of support will improve reproductive healthcare and pregnancy experiences for trans masculine people.
Involved free light chains &lt;10 mg/L with treatment predict better outcomes in systemic light‐chain amyloidosis
Authors: Amandeep Godara, Denis Toskic, Jack Albanese, Benjamin Rosenthal, Nauman S. Siddiqui, Adin Kugelmass, Ping Zhou, Teresa Fogaren, Cindy Varga, Heather J Landau, Raymond L Comenzo
Journal: American Journal of Hematology (2020)