tbuckley/cabot-search huggingface dataset:
Abstract 21: Effects of the Selective NLRP3-Inflammasome Inhibitor MCC950 on Post-Resuscitation Myocardial and Cerebral Function in a Rat Model of Cardiopulmonary Resuscitation
Authors: Guanghui Zheng, Jing Xu, Fenglian He, Juntao Hu, Weiwei Ge, Xianfei Ji, Jennifer Bradley, Mary Ann A Peberdy, Joseph P Ornato, Longyuan Jiang, Tong Wang, Stefano Toldo, Wanchun Tang
Journal: Circulation (2019)

Introduction: NLRP3 inflammasome mediated pyroptosis has been demonstrated to increase myocardial and cerebral ischemia/reperfusion injury. MCC950 is a newly developed highly selective inhibitor of the NLRP3 inflammasome. Hypothesis: MCC950 administered following resuscitation will reduce the severity of post-resuscitation myocardial and cerebral dysfunction and improve duration of survival in a rat model of CPR. Methods: 15 male Sprague-Dawley rats weighting between 450-550 g were randomized into three groups: 1) MCC950 2) Control 3) Sham. Ventricular fibrillation (VF) was induced and untreated for 6 min. CPR was then initiated and continued for 8 min. Resuscitation was attempted with a 4 J defibrillation. Either MCC950 (10mg/kg) or vehicle was administered intraperitoneal (IP) in line with cardiac injury animal studies immediately after return of spontaneous circulation (ROSC). Sham underwent the same surgical procedure without VF and CPR. Sublingual microcirculation was measured at baseline (BL), 3, 6 and 48 hrs after ROSC. Ejection fraction (EF) was measured at BL, 1, 3, 6 and 48 hrs after ROSC. Neurologic Deficit Score (NDS) was recorded at 48 hrs after resuscitation. Results: Post-resuscitation ejection fraction and perfused sublingual vessel density were greater in MCC950 compared to control (p&lt;0.05). NDS was also improved in MCC950 compared to control (110 vs 425, p&lt;0.05). Survival at 48 hrs after ROSC was greater in MCC950 (4/5 vs 1/5, p&lt;0.05). Conclusion: Administration of MCC950 following ROSC mitigates post-resuscitation myocardial and cerebral dysfunction, improves sublingual microcirculation and duration of survival in a rat model of CPR.
Pre-Transplant Serum Claudin-3 Predicts Intestinal Graft-Versus-Host Disease and Non-Relapse Mortality Risk after Allogeneic Hematopoietic Cell Transplantation
Authors: Shernan Holtan, Todd E. DeFor, Armin Rashidi, Alexander Khoruts, Christopher Staley, Lucie M Turcotte, Pamala A. Jacobson, Daniel J. Weisdorf, Margaret L. MacMillan
Journal: Blood (2019)
Role of Chondrocytes in the Development of Rheumatoid Arthritis Via Transmembrane Protein 147–Mediated <scp>NF</scp>‐κB Activation
Authors: Mitsutoshi Ota, Yuki Tanaka, Ikuma Nakagawa, Jing‐Jing Jiang, Yasunobu Arima, Daisuke Kamimura, Tomohiro Onodera, Norimasa Iwasaki, Masaaki Murakami
Journal: Arthritis & Rheumatology (2019)

Objective We have previously reported that the coactivation of NF ‐κB and STAT 3 in nonimmune cells, including synovial fibroblasts, enhances the expression of NF ‐κB target genes and plays a role in chronic inflammation and rheumatoid arthritis ( RA ). This study was undertaken to examine the role of NF ‐κB activation in chondrocytes and better understand the pathogenesis of RA . Furthermore, transmembrane protein 147 ( TMEM 147) was investigated as a representative NF ‐κB activator in chondrocytes. Methods Clinical samples from RA patients were analyzed by immunohistochemistry. Specimens obtained from patients with polydactyly were used as control samples. The functional contribution of chondrocytes and TMEM 147 to arthritis was examined in several murine models of RA . In vitro experiments (quantitative polymerase chain reaction, RNA interference, immunoprecipitation, and confocal microscopy) were performed to investigate the mechanism of action of TMEM 147 in chondrocytes. Results Samples obtained from RA patients and mouse models of RA showed coactivation of NF ‐κB and STAT 3 in chondrocytes ( P &lt; 0.001). This coactivation induced a synergistic expression of NF ‐κB targets in vitro ( P &lt; 0.01). Chondrocyte‐specific deletion of STAT 3 significantly suppressed the development of cytokine‐induced RA ( P &lt; 0.01). TMEM 147 was highly expressed in chondrocytes from RA patient samples and the mouse models of RA. Gene silencing of TMEM 147 or anti‐ TMEM 147 antibody treatment inhibited the cytokine‐mediated activation of NF ‐κB in vitro ( P &lt; 0.01) and suppressed cytokine‐induced RA in vivo ( P &lt; 0.01). Mechanistically, TMEM 147 molecules acted as scaffold proteins for the NF ‐κB complex, which included breakpoint cluster region and casein kinase 2, and enhanced NF ‐κB activity. Conclusion These results suggest that chondrocytes play a role in the development of RA via TMEM 147‐mediated NF ‐κB activation and indicate a novel therapeutic strategy for RA .
Phase I Trial Using CD19/CD22 Bispecific CAR T Cells in Pediatric and Adult Acute Lymphoblastic Leukemia (ALL)
Authors: Liora M Schultz, Lori S Muffly, Jay Y. Spiegel, Sneha Ramakrishna, Nasheed Hossain, Christina Baggott, Bita Sahaf, Shabnum Patel, Juliana Craig, Jenny Yoon, Meena Kadapakkam, Robbie G. Majzner, Matthew J. Frank, Courtney Erickson, Anne Cunniffe Marcy, Michelle Fujimoto, Neehar Bhatia, Everett H Meyer, Katherine A. Kong, Emily Egeler, Sharon Mavroukakis, Haiying Qin, Terry J. Fry, Steven A Feldman, David B Miklos, Crystal L. Mackall, Kara L. Davis
Journal: Blood (2019)
Omalizumab for Atopic Dermatitis
Authors: Ann Chen Wu
Journal: JAMA Pediatrics (2019)

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 Pediatrics 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 Pediatrics journal
INSIGHT 2: Tepotinib plus osimertinib in patients with EGFR-mutant NSCLC having acquired resistance to EGFR TKIs due to MET-amplification: A phase II trial in progress study
Authors: J.C.-H. Yang, B. Ellers-Lenz, J. Straub, A. Johne, Y.-L. Wu
Journal: Annals of Oncology (2019)
Brigatinib vs crizotinib in patients with ALK inhibitor-naive advanced ALK+ NSCLC: Updated results from the phase III ALTA-1L trial
Authors: R. Camidge, H.R. Kim, M.-J. Ahn, J.C.-H. Yang, J.-Y. Han, M.J. Hochmair, K.H. Lee, A. Delmonte, M.R. Garcia Campelo, D.-W. Kim, F. Griesinger, E. Felip, R. Califano, A. Spira, S. Gettinger, M. Tiseo, Q. Ni, P. Zhang, S. Popat
Journal: Annals of Oncology (2019)
Final Overall Survival and Other Efficacy and Safety Results From ASCEND-3: Phase II Study of Ceritinib in ALKi-Naive Patients With ALK-Rearranged NSCLC
Authors: Makoto Nishio, Enriqueta Felip, Sergey Orlov, Keunchil Park, Chong-Jen Yu, Chun-Ming Tsai, Manuel Cobo, Mark McKeage, Wu-Chou Su, Tony Mok, Giorgio V. Scagliotti, David R. Spigel, Kalyanee Viraswami-Appanna, Zhe Chen, Vanessa Q. Passos, Alice T. Shaw
Journal: Journal of Thoracic Oncology (2019)

The phase II, single-arm ASCEND-3 study assessed the efficacy and safety of ceritinib in anaplastic lymphoma kinase (ALK) inhibitor (ALKi)-naive patients with ALK-rearranged NSCLC who had received at least three previous lines of chemotherapy. Here, we report the final efficacy and safety results.Eligible patients (including those with asymptomatic or neurologically stable brain metastases) received oral ceritinib (750 mg/day, fasted). The primary end point was investigator-assessed overall response rate (ORR). Secondary end points were Blinded Independent Review Committee-assessed ORR; investigator- and Blinded Independent Review Committee-assessed overall intracranial response rate, duration of response, time to response, disease control rate, and progression-free survival (PFS); overall survival (OS); and safety. Exploratory end points included patient-reported outcomes.Of the 124 patients enrolled, 122 (98.4%) had received previous antineoplastic medications (31 patients [25.0%] received at least three regimens), and 49 (39.5%) had baseline brain metastases. The median follow-up time (data cutoff: January 22, 2018) was 52.1 (range, 48.4-60.1) months. The investigator-assessed ORR was 67.7% (95% confidence interval [CI]: 58.8-75.9), and the median PFS was 16.6 months (95% CI: 11.0-23.2). The median OS was 51.3 months (95% CI: 42.7-55.3). Most common adverse events (all grades, ≥60% of patients, all-causality) were diarrhea (85.5%), nausea (78.2%), and vomiting (71.8%). Overall, 18 patients (14.5%) had an adverse event leading to treatment discontinuation. Health-related quality of life was maintained during ceritinib treatment.Ceritinib exhibited prolonged and clinically meaningful OS, PFS, and duration of response in chemotherapy-pretreated (at least three lines), ALKi-naive patients with ALK+ NSCLC. The safety profile was consistent with that reported in previous studies.
Correction: A Virus-infected, Reprogrammed Somatic Cell–derived Tumor Cell (VIReST) Vaccination Regime can Prevent Initiation and Progression of Pancreatic Cancer
Authors: Shuangshuang Lu, Zhe Zhang, Pan Du, Louisa S. Chard, Wenli Yan, Margueritte El Khouri, Zhizhong Wang, Zhongxian Zhang, Yongchao Chu, Dongling Gao, Qinxian Zhang, Lirong Zhang, Ai Nagano, Jun Wang, Claude Chelala, Jing Liu, Jiekai Chen, Pentao Liu, Yunshu Dong, Shengdian Wang, Xiaozhu Li, Jianzeng Dong, Nick R. Lemoine, Duanqing Pei, Yaohe Wang
Journal: Clinical Cancer Research (2021)

In the original version of [this article][1] ([1][2]), five immunofluorescence panels in Fig. 3A were incorrect: DE-KPC-Oct4/DAPI, PPLC-KPC-Nanog/DAPI, PPLC-KPC-Sox17/DAPI, PPLC-WT-KP-Nanog/DAPI, and PPLC-WT-KP-Sox17/DAPI. In addition, the legend for Fig. 2E did not provide clarification about the
Introducing the Endotype Concept to Address the Challenge of Disease Heterogeneity in Type 1 Diabetes
Authors: Manuela Battaglia, Simi Ahmed, Mark S. Anderson, Mark A. Atkinson, Dorothy Becker, Polly J. Bingley, Emanuele Bosi, Todd M. Brusko, Linda A. DiMeglio, Carmella Evans-Molina, Stephen E. Gitelman, Carla J. Greenbaum, Peter A. Gottlieb, Kevan C. Herold, Martin J. Hessner, Mikael Knip, Laura Jacobsen, Jeffrey P. Krischer, S. Alice Long, Markus Lundgren, Eoin F. McKinney, Noel G. Morgan, Richard A. Oram, Tomi Pastinen, Michael C. Peters, Alessandra Petrelli, Xiaoning Qian, Maria J. Redondo, Bart O. Roep, Desmond Schatz, David Skibinski, Mark Peakman
Journal: Diabetes Care (2019)

The clinical diagnosis of new-onset type 1 diabetes has, for many years, been considered relatively straightforward. Recently, however, there is increasing awareness that within this single clinical phenotype exists considerable heterogeneity: disease onset spans the complete age range; genetic susceptibility is complex; rates of progression differ markedly, as does insulin secretory capacity; and complication rates, glycemic control, and therapeutic intervention efficacy vary widely. Mechanistic and immunopathological studies typically show considerable patchiness across subjects, undermining conclusions regarding disease pathways. Without better understanding, type 1 diabetes heterogeneity represents a major barrier both to deciphering pathogenesis and to the translational effort of designing, conducting, and interpreting clinical trials of disease-modifying agents. This realization comes during a period of unprecedented change in clinical medicine, with increasing emphasis on greater individualization and precision. For complex disorders such as type 1 diabetes, the option of maintaining the "single disease" approach appears untenable, as does the notion of individualizing each single patient's care, obliging us to conceptualize type 1 diabetes less in terms of phenotypes (observable characteristics) and more in terms of disease endotypes (underlying biological mechanisms). Here, we provide our view on an approach to dissect heterogeneity in type 1 diabetes. Using lessons from other diseases and the data gathered to date, we aim to delineate a roadmap through which the field can incorporate the endotype concept into laboratory and clinical practice. We predict that such an effort will accelerate the implementation of precision medicine and has the potential for impact on our approach to translational research, trial design, and clinical management.
Dealing With the Tension Between the Patient’s Wish to Die and Professional Attitudes Toward a ‘Good Death’
Authors: Suzanne Metselaar, Guy Widdershoven
Journal: The American Journal of Bioethics (2019)

"Dealing With the Tension Between the Patient’s Wish to Die and Professional Attitudes Toward a ‘Good Death’." The American Journal of Bioethics, 19(12), pp. 44–45
Purity Independent Subtyping of Tumors (PurIST), A Clinically Robust, Single-sample Classifier for Tumor Subtyping in Pancreatic Cancer
Authors: Naim U. Rashid, Xianlu L. Peng, Chong Jin, Richard A. Moffitt, Keith E. Volmar, Brian A. Belt, Roheena Z. Panni, Timothy M. Nywening, Silvia G. Herrera, Kristin J. Moore, Sarah G. Hennessey, Ashley B. Morrison, Ryan Kawalerski, Apoorve Nayyar, Audrey E. Chang, Benjamin Schmidt, Hong Jin Kim, David C. Linehan, Jen Jen Yeh
Journal: Clinical Cancer Research (2019)

Abstract Purpose: Molecular subtyping for pancreatic cancer has made substantial progress in recent years, facilitating the optimization of existing therapeutic approaches to improve clinical outcomes in pancreatic cancer. With advances in treatment combinations and choices, it is becoming increasingly important to determine ways to place patients on the best therapies upfront. Although various molecular subtyping systems for pancreatic cancer have been proposed, consensus regarding proposed subtypes, as well as their relative clinical utility, remains largely unknown and presents a natural barrier to wider clinical adoption. Experimental Design: We assess three major subtype classification schemas in the context of results from two clinical trials and by meta-analysis of publicly available expression data to assess statistical criteria of subtype robustness and overall clinical relevance. We then developed a single-sample classifier (SSC) using penalized logistic regression based on the most robust and replicable schema. Results: We demonstrate that a tumor-intrinsic two-subtype schema is most robust, replicable, and clinically relevant. We developed Purity Independent Subtyping of Tumors (PurIST), a SSC with robust and highly replicable performance on a wide range of platforms and sample types. We show that PurIST subtypes have meaningful associations with patient prognosis and have significant implications for treatment response to FOLIFIRNOX. Conclusions: The flexibility and utility of PurIST on low-input samples such as tumor biopsies allows it to be used at the time of diagnosis to facilitate the choice of effective therapies for patients with pancreatic ductal adenocarcinoma and should be considered in the context of future clinical trials.
Abstract 12238: Myocardial Injury Induces Renal Fibrosis and Dysfunction in Association With the Activation of Renal Apoptotic and TGF-Beta Molecular Pathways
Authors: S. J Sangaralingham, Fernando L Martin, Brenda K Huntley, Tomoko Ichiki, Horng H Chen, John C Burnett
Journal: Circulation (2015)

Introduction: Human and experimental studies have suggested that a decline in renal function after myocardial infarction (MI), possibly due to the activation of adverse molecular pathways, contributes to heart failure (HF) progression and poor outcomes. The apoptosis and the transforming growth factor-beta (TGF-beta) pathways have been implicated in post-MI injury, however it is unclear if these 2 key pathways are activated post-MI in the kidney and may contribute to renal fibrosis and dysfunction. Hypothesis: We hypothesized that MI activates widespread renal apoptotic and TGF-beta related genes and is associated with renal fibrosis and dysfunction. Methods: Wistar rats were randomized into two groups: Sham-operated (S; n=10) and MI (produced by left coronary artery ligation; n=10). Cardiorenal structure and function were assessed at 3 weeks and included mean arterial pressure (MAP), EF, GFR, renal blood flow (RBF), sodium (Na) excretion and renal fibrosis by picrosirius red staining. Microarray analysis (Affymetrix GeneChip Rat Genome) was performed on kidney cortex (KC) and medulla (KM) and focused on apoptotic and TGF-beta related genes. Data presented as mean±SE,*p&lt;0.05. Results: Experimental MI was characterized by a significant decrease in EF (S: 79±1, MI: 49±4 %*) and LV hypertrophy (S: 2.06±0.03, MI: 2.57±0.07 mg/g*), while MAP did not differ between groups. GFR and Na excretion were similar between the groups, however there was a significant decline in post-MI RBF (S: 14±1, MI: 8±1 ml/min*). Notably, after MI the KC (S: 1.3±0.3, MI: 3.4±0.8 %*) and KM (S: 1.0±0.3, MI: 11±2.8 %*) exhibited an increase in fibrosis. Microarray analysis revealed that 138 apoptotic and 15 TGF-beta pathway genes in the KC and 122 apoptotic and 10 TGF-beta pathway genes in the KM were significantly altered (1.5 fold, p&lt;0.05) in the MI group. Conclusions: These findings demonstrate that MI results in adverse renal fibrotic remodeling together with extensive modulation of apoptotic and TGF-beta pathways of which may contribute to post-MI renal dysfunction. This study suggests that therapies should target detrimental molecular pathways in the kidney as well the heart to prevent the progression of post-MI cardiorenal failure.
Does polygenic risk influence associations between sun exposure and melanoma? A prospective cohort analysis
Authors: C.M. Olsen, N. Pandeya, M.H. Law, S. MacGregor, M.M. Iles, B.S. Thompson, A.C. Green, R.E. Neale, D.C. Whiteman
Journal: British Journal of Dermatology (2019)

Background Melanoma develops as the result of complex interactions between sun exposure and genetic factors. However, data on these interactions from prospective studies are scant. Objectives To quantify the association between ambient and personal ultraviolet exposure and incident melanoma in a large population-based prospective study of men and women residing in a setting of high ambient ultraviolet radiation, and to examine potential gene–environment interactions. Methods Data were obtained from the QSkin Sun and Health Study, a prospective cohort study of men and women aged 40–69 years, randomly sampled from the Queensland population in 2011. Participants were genotyped and assessed for ultraviolet exposure. Results Among participants with genetic data (n = 15 373), 420 (2·7%) developed cutaneous melanoma (173 invasive, 247 in situ) during a median follow-up time of 4·4 years. Country of birth, age at migration, having > 50 sunburns in childhood or adolescence, and a history of keratinocyte cancer or actinic lesions were significantly associated with melanoma risk. Conclusions An interaction with polygenic risk was suggested: among people at low polygenic risk, markers of cumulative sun exposure (as measured by actinic damage) were associated with melanoma. In contrast, among people at high polygenic risk, markers of high-level early-life ambient exposure (as measured by place of birth) were associated with melanoma (hazard ratio for born in Australia vs. overseas 3·16, 95% confidence interval 1·39–7·22). These findings suggest interactions between genotype and environment that are consistent with divergent pathways for melanoma development. What's already known about this topic? The relationship between sun exposure and melanoma is complex, and exposure effects are highly modified by host factors and behaviours. The role of genotype on the relationship between ultraviolet radiation exposure and melanoma risk is poorly understood. What does this study add? We found that country of birth, age at migration, sunburns in childhood or adolescence, and history of keratinocyte cancer or actinic lesions were significantly associated with melanoma risk, while other measures of continuous or more intermittent patterns of sun exposure were not. We found evidence for gene–environment interactions that are consistent with divergent pathways for melanoma development. Linked Comment: Cust. Br J Dermatol 2020; 183:205–206.
A reply letter to: “A commentary on “continuous adductor canal block is a better choice compared to single shot after primary total knee arthroplasty: A meta-analysis of randomized controlled trials” (Int J Surg 2019 Oct 12. pii: S1743-9191(19)30277–8. doi: 10.1016/j.ijsu.2019.10.012. [Epub ahead of print]”
Authors: Jie Zhao, Zhenming Kang
Journal: International Journal of Surgery (2019)
Apalutamide (APA) plus androgen deprivation therapy (ADT) for metastatic castration-sensitive prostate cancer (mCSPC): Analysis of pain and fatigue in the TITAN study
Authors: B.H. Chung, K. McQuarrie, A. Bjartell, S. Chowdhury, A.J. Pereira de Santana Gomes, M. Özgüroğlu, Á. Juárez Soto, A.S. Merseburger, H. Uemura, D. Ye, R. Given, B. Miladinovic, N. Li, S. Hudgens, L. Floden, A. Lopez-Gitlitz, K.N. Chi, N. Agarwal
Journal: Annals of Oncology (2019)
NRG1-fusion-driven solid tumours: A case series indicating the therapeutic potential of afatinib
Authors: Y. Goto, J. Cadranel, B.A. Weinberg, M. Duruisseaux, S.V. Liu, K. Tolba, E. Branden, R.C. Doebele, C. Heining, R.F. Schlenk, J.J. Laskin, P.K. Cheema, M.R. Jones, D. Trombetta, L.A. Muscarella, A. Cseh, F. Solca, D.J. Renouf
Journal: Annals of Oncology (2019)
Eye problems in contact lens wearers
Authors: Syed M Shahid, Syed N Ahmed, Yusra Khan
Journal: BMJ (2019)

### What you need to know

More than 140 million people worldwide wear contact lenses.1 Contact lens wearers are more prone to ocular surface problems, particularly those who use extended wear contact lenses.23 Patients may present to the general practitioner, pharmacist, or optometrist in approximately 42% of cases.4 Clinicians in acute care need to be able to identify sight threatening conditions such as microbial keratitis, and advise on more common problems such as a retained contact lens or contact lens discomfort. This article outlines the common eye conditions associated with contact lens wear and an approach that non-specialists can use to identify and manage them.

Accurate diagnosis and treatment of contact lens related problems in the non-specialist setting is challenging. Firstly, in the case of someone presenting with a red eye, the wide differential diagnosis of the red eye has to be considered in addition to the specific contact lens related complications described in this article.5 Secondly, a slit lamp is required to confirm the diagnosis in most cases. As such, in primary care an assessment may be limited to identifying a likely cause, and making a judgment about the risk of a serious or sight threatening complications and need for urgent eye specialist assessment. Forming this judgment is summarised in figure 1. We recommend that if a clinician is uncertain about the diagnosis, they should seek further advice from an eye specialist. Advise patients to abstain from using contact lenses while awaiting specialist …