tbuckley/cabot-search huggingface dataset:
Peripheral blood biomarkers associated with outcome in non-small cell lung cancer patients treated with nivolumab and durvalumab monotherapy.
Authors: Lin Wu, Meilin Jiang, Wenying Peng, Xingxiang Pu, Bolin Chen, Jia Li, Fang Xu, Li Xu, Yan Xu, Jingyi Wang
Journal: Journal of Clinical Oncology (2020)

e21732 Background: Selecting patients that potentially benefit from immune checkpoint inhibitors (ICIs) is critical. Programmed death ligand-1 (PD-L1) protein immunohistochemical expression on cancer cells or immune cells and Next generation sequencing based tumor mutational burden (TMB) are the hot spots in studies on ICIs, but there is still confusion in the testing methods. Due to blood samples are much easier for clinical application, many potential peripheral biomarkers have been proposed. This study identify blood parameters that associated with outcome of non-small cell lung cancer (NSCLC) patients with ICIs monotherapy. Methods: Data of 76 NSCLC patients were analyzed retrospectively. To assess the connection between survival and peripheral blood markers measured before and after treatment, we utilized COX regression model survival analysis and receiver operating characteristic (ROC) curve to assess the markers. Results: In the nivolumab cohort, the optimal cutoff for predicting 11 month overall survival (OS) were 168.13 and 43g/L in Plateletto-lymphocyte ratio (PLR) and albumin, respectively. When patients are grouped with PLR and albumin the cut-offs, a significant difference in SD-PR vursus PD rate were found between high and low groups, separately. which was not found when grouped by PD-L1 expression. Patients with high PLR ( &gt; 168.13) or low albumin ( &lt; = 43g/L) before ICI had a significantly raised hazard of progression, separately (for PLR, P = 0.006; for albumin, P = 0.033) and of death (for PLR, P = 0.014; for albumin, P = 0.009) compared with those patients who had low PLR or albumin level. More importantly, we found that higher PLR ( &gt; 168.13) after the fourth cycle of ICIs was also an prognostic biomarker, which significantly correlated with shorter OS in both Nivolumab (P = 0.046) and durvalumab cohort (P = 0.028). Conclusions: PLR and albumin may help the stratification of high progression and death risk group in advanced NSCLC patients treated with nivolumab and durvalumab monotherapy.
A Phase I Study of GSK525762, a Selective Bromodomain (BRD) and Extra Terminal Protein (BET) Inhibitor: Results from Part 1 of Phase I/II Open Label Single Agent Study in Patients with Acute Myeloid Leukemia (AML)
Authors: Mark Dawson, Eytan M. Stein, Brian J.P Huntly, Anastasios Karadimitris, Manali Kamdar, Carlos Fernandez de Larrea, Michael J. Dickinson, Paul Sung-Hao Yeh, Naval Daver, Aristeidis Chaidos, Martin S. Tallman, Raquel Jiménez, Thierry Horner, January Baron, John Brennan, Geraldine Ferron-Brady, Yuehui Wu, Natalie Karpinich, Brandon Kremer, Arindam Dhar, Gautam Borthakur
Journal: Blood (2017)
Factors Influencing Management of Anticoagulation in Thrombocytopenic Patients with Hematological Malignancy
Authors: Avi Leader, Vincent ten Cate, Arina ten Cate-Hoek, Erik Am Beckers, Galia Spectre, Pia Raanani, Harry C. Schouten, Anna Falanga, Hugo ten Cate
Journal: Blood (2017)
Self-assembling peptide hydrogels functionalized with LN- and BDNF- mimicking epitopes synergistically enhance peripheral nerve regeneration
Authors: Shuhui Yang, Chong Wang, Jinjin Zhu, Changfeng Lu, Haitao Li, Fuyu Chen, Jiaju Lu, Zhe Zhang, Xiaoqing Yan, He Zhao, Xiaodan Sun, Lingyun Zhao, Jing Liang, Yu Wang, Jiang Peng, Xiumei Wang
Journal: Theranostics (2020)

The regenerative capacity of the peripheral nervous system is closely related to the role that Schwann cells (SCs) play in construction of the basement membrane containing multiple extracellular matrix proteins and secretion of neurotrophic factors, including laminin (LN) and brain-derived neurotrophic factor (BDNF). Here, we developed a self-assembling peptide (SAP) nanofiber hydrogel based on self-assembling backbone Ac-(RADA)
A phase 0 trial of riluzole in patients with resectable stage III or IV melanoma.
Authors: Dana Yip, Maithao Le, Jonathan Lee, Suzie Chen, James Goydos
Journal: Cancer Research (2008)

LB-244  Abstract LB-244 was submitted as a Late-Breaking Abstract and is embargoed until the time of presentation. The complete abstract will be posted to this site at or after the following date and time: 4/15/2008 1:00 PM.
Notch signaling contributes to the establishment of sustained unresponsiveness to food allergens by oral immunotherapy
Authors: Toshiyuki Yoneyama, Nobuhiro Nakano, Mutsuko Hara, Hiromichi Yamada, Kumi Izawa, Koichiro Uchida, Ayako Kaitani, Tomoaki Ando, Jiro Kitaura, Yoshikazu Ohtsuka, Hideoki Ogawa, Ko Okumura, Toshiaki Shimizu
Journal: Journal of Allergy and Clinical Immunology (2020)
Dr. Mladen Vranic—A Legend in Diabetes Research: 1930–2019
Authors: Alan Cherrington, Shirya Rashid
Journal: Diabetes Care (2020)

Mladen Vranic, MD, DSc, FRSC, FRCP(C), FCAHS, was an early pioneer in the field of diabetes, greatly advancing our understanding of diabetes physiology. Over the course of his scientific career, Dr. Vranic changed the landscape of diabetes research in North America and internationally through his groundbreaking work in glucose metabolism, exercise, stress, and hypoglycemia. It is noteworthy that he trained as the last postdoctoral fellow of Dr. Charles Best, a codiscoverer of insulin, at the University of Toronto. 

Dr. Vranic’s interest in diabetes research started during his early life, as did his determination to thrive despite deep struggles. He was born 30 April 1930 to Vladamir and Ana Vranic in Zagreb, Croatia. His father was a professor at the Faculty of Economics, Engineering, and Sciences and dean at the School of Economics and Engineering at the University of Zagreb. His teaching specialty was mathematics. Mladen was an only child, of Jewish heritage, and a Holocaust survivor. He and his family narrowly escaped capture by the Nazis multiple times during World War II. As a young boy he, his parents, and his grandmother sought refuge in Italy, managing to flee just ahead of their would-be captors. Despite their efforts, they were eventually caught and sent to a concentration camp when Mladen was 11. He attributed his survival there to his and his family’s undeterred tenacity to endure and escape. 



Mladen Vranic



Upon completing medical school at the University of Zagreb, Mladen pursued graduate studies in physiology, with a focus on diabetes, the only specialty available in the department at the time. Concomitantly, his father developed type 2 diabetes. Mladen said about the field that was to become his life’s work and passion, “I have never regretted for one instant my commitment to a life in medical research and education” and “diabetes …
Focal pancreatic lesions in autoimmune pancreatitis and weight loss
Authors: Ali Aghdassi, Quang Trung Tran, Thomas Bulla, Robin Bülow, Silvia Ribback, Markus M Lerch, Tilman Pickartz
Journal: Gut (2020)

A 67-year-old male patient was admitted to hospital with upper abdominal pain, jaundice and pale stool for 2 weeks. Laboratory investigation showed highly elevated cholestatic parameters and transaminases but no increase of serum IgG4. MRI (figure 1) and endoscopic ultrasound (EUS) demonstrated a diffuse enlargement of the pancreas. Parenchymal biopsy taken by EUS-guided fine needle aspiration (FNA) contained storiform fibrosis with increased plasma cells expressing IgG4 (>30 cells/HPF) compatible with autoimmune pancreatitis type I. A steroid pulse therapy was initiated followed by maintenance therapy (prednisolone 5 mg/kg p.o.) and the patient recovered. One year later, the patient presented again with weight loss. …
Intravascular Microaxial Left Ventricular Assist Device vs Intra-aortic Balloon Pump for Cardiogenic Shock
Authors: John A. Rizzo, Henry Dove
Journal: JAMA (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 HomeNew OnlineCurrent IssueFor Authors 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
lnc-BAZ2B promotes M2 macrophage activation and inflammation in children with asthma through stabilizing BAZ2B pre-mRNA
Authors: Li Xia, Xiang Wang, Lijuan Liu, Jinrong Fu, Wenfeng Xiao, Qiuyan Liang, Xiao Han, Saihua Huang, Licheng Sun, Yajing Gao, Caiyan Zhang, Lan Yang, Libo Wang, Liling Qian, Yufeng Zhou
Journal: Journal of Allergy and Clinical Immunology (2020)
Association of inflammatory biomarkers with clinical outcomes in nivolumab-treated patients with advanced hepatocellular carcinoma
Authors: Bruno Sangro, Ignacio Melero, Samir Wadhawan, Richard S. Finn, Ghassan K. Abou-Alfa, Ann-Lii Cheng, Thomas Yau, Junji Furuse, Joong-Won Park, Zachary Boyd, Hao (Tracy) Tang, Yun Shen, Marina Tschaika, Jaclyn Neely, Anthony El-Khoueiry
Journal: Journal of Hepatology (2020)

Nivolumab, a programmed death (PD)-1 (PD-1) inhibitor, led to durable responses, manageable safety, and increased survival in patients with advanced hepatocellular carcinoma (HCC). In our retrospective analysis, we studied the immunobiology and potential associations between biomarkers and outcomes with nivolumab in HCC.Fresh and archival tumour samples from dose-escalation and dose-expansion phases of the CheckMate 040 trial were analysed by immunohistochemistry and RNA sequencing to assess several inflammatory gene expression signatures, including CD274 (PD-ligand 1 [PD-L1]), CD8A, LAG3, and STAT1. Biomarkers were assessed for association with clinical outcomes (best overall response by blinded independent central review per RECIST v1.1 and overall survival [OS]).Complete or partial tumour responses were observed in PD-L1-positive and PD-L1-negative patients treated with nivolumab monotherapy. Median OS was 28.1 (95% CI 18.2-n.a.) vs. 16.6 months (95% CI 14.2-20.2) for patients with tumour PD-L1 ≥1% vs. <1% (p = 0.03). Increased CD3 and CD8 showed a non-significant trend towards improved OS (both p = 0.08), and macrophage markers were not associated with OS. Tumour PD-1 and PD-L1 expression were associated with improved OS (p = 0.05 and p = 0.03, respectively). An inflammatory gene signature consisting of 4 genes was associated with improved objective response rate (p = 0.05) and OS (p = 0.01).PD-1 and PD-L1 expression, biomarkers of inflammation, and inflammatory gene signatures trended with improved survival and response. While further confirmation within a larger phase III trial is needed to evaluate predictive value of these biomarkers, these exploratory analyses suggest that anti-tumour immune response may play a role in the treatment benefit of nivolumab in HCC.Certain tests may be used to provide a picture of how a tumour is escaping the immune system, allowing it to continue to grow and create more tumours. Therapies such as nivolumab are designed to help the immune system fight the tumour. These tests may be used to determine how effective such therapies will be in the treatment of advanced liver cancer.NCT01658878.
Metatranscriptomic assessment of burn wound infection clearance
Authors: Teija Ojala, Andrew Lindford, Kirsi Savijoki, Heli Lagus, Jenni Tommila, Alan Medlar, Pentti Kuusela, Pekka Varmanen, Liisa Holm, Jyrki Vuola, Esko Kankuri, Matti Kankainen
Journal: Clinical Microbiology and Infection (2020)
SAT0244 PROGNOSIS OF LARGE VESSEL INVOLVEMENT IN LARGE VESSEL VASCULITIS
Authors: M. Vautier, A. Dupont, H. De Boysson, C. Comarmond, T. Mirault, A. Mekinian, M. Lambert, Y. Ferfar, A. Aouba, P. Cacoub, M. Resche-Rigon, D. Saadoun
Journal: Annals of the Rheumatic Diseases (2020)

Background: Giant cell arteritis (GCA) and Takayasu arteritis (TAK) are the two main forms of large vessels vasculitis (LVV). Vessel inflammation leads to aneurysms, wall thickening, stenosis, and, in some cases, complete occlusion of the artery. Due to the wide variation in the course of LVV, predicting outcome is challenging. To our knowledge, data regarding prognosis factors of LVI in LVV patients and comparison of outcome of LVI in GCA and TAK are lacking. An early identification of patients with higher mortality could help to prevent deaths and vascular complications. Objectives: To assess prognosis factors and outcome of large vessel involvement (LVI) in large vessels vasculitis (LVV) patients. Methods: Retrospective multicenter study of characteristics and outcomes of 417 patients with LVI including 299 Takayasu arteritis (TAK) and 118 Giant cell arteritis (GCA-LVI) were analyzed. Logistic regression analysis assessed prognosis factors in LVV patients. Outcome of LVI among TAK and GCA-LVI patients (ischemic complications, aneurysms complications, relapses and revascularization) were assessed. Results: In multivariable analysis, stroke/transient ischemic attack [HR: 3.63 (1.46 - 9.04), p=0.006] was independently associated with vascular complications in LVV. The 10-years aneurysm free survival was significantly lower [67% (48 – 93) vs 89% (84 – 95), p=0.02] in GCA-LVI compare to TAK patients. The 5-years relapse free survival was significantly lower [47% (37 – 60) vs 69% (63 – 75), p&lt;0.001,] in GCA-LVI compare to TAK patients. The 10-years revascularization free survival was significantly lower [55% (48 – 64) vs 76% (59 – 99), p&lt;0.001] in TAK compare to GCA-LVI patients. After a median follow-up of 5 years, 16 (5.4%) TAK and 7 (5.9%) GCA-LVI patients died, mainly of aneurysm (26%) and ischemic complications (26%). Conclusion: This large nationwide cohort of LVI provided prognosis factors of vascular complications in LVV patients. TAK and GCA-LVI have different long-term outcome in term of aneurysm development, relapse and revascularization. Disclosure of Interests: None declared
Optimizing Treatment for Head and Neck Cancers: Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma
Authors: Robert I. Haddad
Journal: Journal of the National Comprehensive Cancer Network (2020)

Immunotherapy has changed the game in the treatment of head and neck cancer (HNC). Practice-changing results from the phase III KEYNOTE-048 trial led to the approval of pembrolizumab immunotherapy alone or in combination with chemotherapy for the treatment of recurrent/metastatic HNC in the first-line setting. Testing for combined positive score (CPS) is now part of routine practice, because patients with CPS ≥1 can be started on single-agent immunotherapy in the first-line. Pembrolizumab replaces the “old” standard of care established by the EXTREME study, as trials looking at targets besides immunotherapy have proved “disappointing.” Additionally, nivolumab and pembrolizumab are both approved for use in the second-line.
Primary care assessment and management of common physical symptoms in pregnancy
Authors: Meena Bhatia, Kamal R Mahtani, Ruby Rochman, Sally L Collins
Journal: BMJ (2020)

<h3>BACKGROUND:</h3> More patients with cystic fibrosis (CF) are living longer, and lifestyle-related behavior is becoming increasingly important for improving morbidity and mortality. Declining levels of exercise leads to low cardiorespiratory fitness, which is a strong, independent predictor of mortality in patients with CF. As a result, exercise training has become a commonly accepted form of treatment for patients with CF. The purpose of this study was to determine physical activity levels and perception of exercise in adult patients with CF. <h3>METHODS:</h3> Adult patients from an in-patient CF unit were recruited to participate. A structured interview and self-report questionnaires were used to collect information on levels of physical activity and exercise perception including preferences, readiness, and barriers. <h3>RESULTS:</h3> Forty-six adult patients with CF consented to participate in the interview and completed self-report questionnaires. Subjects self-reported that the majority (84%) of their time was spent performing physical activity at a moderate level, with mean ± SD of 11.8 ± 12.2 h per week of moderate physical activity. Vigorous physical activity was described as hard and very hard physical activity, with a mean ± SD of 1.8 ± 4.6 h (13%) and 0.4 ± 1.6 h (3%), respectively. Most of the adult subjects with CF preferred walking, and 65% of them felt that exercise was very important. Lack of energy, lack of good health, lack of self-discipline, and lack of time were noted as the most frequent barriers to exercise. <h3>CONCLUSIONS:</h3> In this study, adult subjects with CF self-reported performing an adequate amount of moderate physical activity, although only a small proportion of time was spent at a vigorous level of physical activity. Clinicians providing rehabilitation have an opportunity to improve adherence to prescribed exercise by understanding the impact that physiological and psychological factors have on patients with CF. Further, motivating patients with CF to engage in more vigorous physical activity may provide a stimulus that improves clinical outcomes and potentially survival.
Abstract MP66: Skeletal Muscle Adipose Tissue is Associated with Coronary Artery Calcification: The CARDIA Study
Authors: James G Terry, James Lovato, Christina M Shay, Jared Reis, Samuel S Gidding, Pamela J Schreiner, David C Goff, David R Jacobs, J J Carr
Journal: Circulation (2013)

Ectopic fat within skeletal muscles, liver, and around the heart may play a role in cardiovascular disease (CVD) risk. It is unclear if associations of ectopic adipose tissues with CVD risk are ind...
Self-accelerating H<sub>2</sub>O<sub>2</sub>-responsive Plasmonic Nanovesicles for Synergistic Chemo/starving therapy of Tumors
Authors: Yao Tang, Yuejia Ji, Chenglin Yi, Di Cheng, Bin Wang, Yun Fu, Yufang Xu, Xuhong Qian, Yahya E. Choonara, Viness Pillay, Weiping Zhu, Yunen Liu, Zhihong Nie
Journal: Theranostics (2020)

Rationale: Nanoscale vehicles responsive to abnormal variation in tumor environment are promising for use in targeted delivery of therapeutic drugs specifically to tumor sites. Herein, we report the design and fabrication of self-accelerating H2O2-responsive plasmonic gold nanovesicles (GVs) encapsulated with tirapazamine (TPZ) and glucose oxidase (GOx) for synergistic chemo/starving therapy of cancers. Methods: Gold nanoparticles were modified with H2O2-responsive amphiphilic block copolymer PEG45-b-PABE330 by ligand exchange. The TPZ and GOx loaded GVs (TG-GVs) were prepared through the self-assembly of PEG45-b-PABE330 -grafted nanoparticles together with TPZ and GOx by solvent displacement method. Results: In response to H2O2 in tumor, the TG-GVs dissociate to release the payloads that are, otherwise, retained inside the vesicles for days without noticeable leakage. The released GOx enzymes catalyze the oxidation of glucose by oxygen in the tumor tissue to enhance the degree of hypoxia that subsequently triggers the reduction of hypoxia-activated pro-drug TPZ into highly toxic free radicals. The H2O2 generated in the GOx-catalyzed reaction also accelerate the dissociation of vesicles and hence the release rate of the cargoes in tumors. The drug-loaded GVs exhibit superior tumor inhibition efficacy in 4T1 tumor-bearing mice owing to the synergistic effect of chemo/starvation therapy, in addition to their use as contrast agents for computed tomography imaging of tumors. Conclusion: This nanoplatform may find application in managing tumors deeply trapped in viscera or other important tissues that are not compatible with external stimulus (e.g. light).
PSCs Reveal PUFA-Provoked Mitochondrial Stress as a Central Node Potentiating RPE Degeneration in Bietti’s Crystalline Dystrophy
Authors: Zhao Zhang, Bin Yan, Fei Gao, Qing Li, Xiaohong Meng, Peikai Chen, Lei Zhou, Wen Deng, Cheng Li, Weiyi Xu, Shuo Han, Hong Feng, Yaping Li, Junhui Chen, Zhengqin Yin, Can Liao, Hung-Fat Tse, Aimin Xu, Qizhou Lian
Journal: Molecular Therapy (2020)

Bietti's crystalline dystrophy (BCD) is an incurable retinal disorder caused by the polypeptide 2 of cytochrome P450 family 4 subfamily V (CYP4V2) mutations. Patients with BCD present degeneration of retinal pigmented epithelial (RPE) cells and consequent blindness. The lack of appropriate disease models and patients' RPE cells limits our understanding of the pathological mechanism of RPE degeneration. In this study, using CYP4V2 mutant pluripotent stem cells as disease models, we demonstrated that RPE cells with CYP4V2 mutations presented a disrupted fatty acid homeostasis, which were characterized with excessive accumulation of poly-unsaturated fatty acid (PUFA), including arachidonic acid (AA) and eicosapentaenoic acid (EPA). The PUFA overload increased mitochondrial reactive oxygen species, impaired mitochondrial respiratory functions, and triggered mitochondrial stress-activated p53-independent apoptosis in CYP4V2 mutant RPE cells. Restoration of the mutant CYP4V2 using adeno-associated virus 2 (AAV2) can effectively reduce PUFA deposition, alleviate mitochondria oxidative stresses, and rescue RPE cell death in BCD RPE cells. Taken together, our results highlight a role of PUFA-induced mitochondrial damage as a central node to potentiate RPE degeneration in BCD patients. AAV2-mediated gene therapy may represent a feasible strategy for the treatment of BCD. Bietti's crystalline dystrophy (BCD) is an incurable retinal disorder caused by the polypeptide 2 of cytochrome P450 family 4 subfamily V (CYP4V2) mutations. Patients with BCD present degeneration of retinal pigmented epithelial (RPE) cells and consequent blindness. The lack of appropriate disease models and patients' RPE cells limits our understanding of the pathological mechanism of RPE degeneration. In this study, using CYP4V2 mutant pluripotent stem cells as disease models, we demonstrated that RPE cells with CYP4V2 mutations presented a disrupted fatty acid homeostasis, which were characterized with excessive accumulation of poly-unsaturated fatty acid (PUFA), including arachidonic acid (AA) and eicosapentaenoic acid (EPA). The PUFA overload increased mitochondrial reactive oxygen species, impaired mitochondrial respiratory functions, and triggered mitochondrial stress-activated p53-independent apoptosis in CYP4V2 mutant RPE cells. Restoration of the mutant CYP4V2 using adeno-associated virus 2 (AAV2) can effectively reduce PUFA deposition, alleviate mitochondria oxidative stresses, and rescue RPE cell death in BCD RPE cells. Taken together, our results highlight a role of PUFA-induced mitochondrial damage as a central node to potentiate RPE degeneration in BCD patients. AAV2-mediated gene therapy may represent a feasible strategy for the treatment of BCD.