tbuckley/cabot-search huggingface dataset:
Effect of age on impact of adjuvant chemotherapy for resected non-small cell lung cancer.
Authors: Apar Kishor Ganti, Christina D. Williams, Ajeet Gajra, Michael J. Kelley
Journal: Journal of Clinical Oncology (2013)

7539 Background: Adjuvant chemotherapy (AC) is considered standard of care in patients with resected stages 2 and 3 non-small cell lung cancer (NSCLC). However data regarding its utility in older patients are sparse. This analysis was conducted to evaluate the role of AC in older patients with early stage NSCLC. Methods: We conducted a retrospective analysis of patients with stages 1-3 NSCLC between 2001 and 2008 in the VA Central Cancer Registry. Patients were divided into two groups based on age: &lt;70 yrs and ≥70 yrs. Descriptive statistics were used to examine patterns of AC use and to obtain survival rates associated with use of AC in the two age groups. Chi-square was used to compare distributions. Results: Of the 10,036 patients who underwent surgical resection, 3958 (39.4%) were ≥70 yrs, while 6078 were &lt;70 yrs old. Overall, 11.2% of older patients (6.3% - stage 1, 21% - stage 2, 26.2% - stage 3) and 22.3% of younger pts (11.6% - stage 1, 41.1% - stage 2, 47.1% - stage 3) received AC. Of the patients who received AC, a greater proportion of younger patients received platinum-based AC (91.8 vs 86.4% vs; p=0.0008). Also, in each stage younger patients had a better 3 yr overall survival (OS) (Stage 1-69.2 vs 58%, stage 2 – 52.8 vs 39.1%, stage 3 – 42.5 vs 33.7%). Younger patients with stages 2 and 3 NSCLC who received AC had improved 3 yr OS (58.8 vs 48.6%; p=0.0009 and 48.8 vs 36.9%; p=0.0002 respectively). There was no difference in 3 yr OS for older patients based on AC when all stages were included. For patients with stages 2 and 3, a larger proportion of younger patients received cisplatin-based AC (11.3 vs 3.5%). Older patients with stages 2 and 3, who received cisplatin-based AC had a better 3 yr OS compared to those who received carboplatin-based AC or no AC (55.3 vs 42.2 vs 35.3% respectively; p=0.01). Similarly cisplatin-based AC had an improved 3 yr OS in younger patients with stages 2 and 3 NSCLC (61.4 vs 52 vs 43.4% respectively; p=0.0001). Conclusions: This analysis suggests that older patients do not benefit from AC after resection of stage 1-3 NSCLC to the same degree as younger patients. This differential effect may be due to less common use of cisplatin among older patients. Multivariate analyses are planned.
Fundamental insights in PLGA degradation from thin film studies
Authors: Rainhard Machatschek, Andreas Lendlein
Journal: Journal of Controlled Release (2019)

Poly(lactide-co-glycolide)s are commercially available degradable implant materials, which are typically selected based on specifications given by the manufacturer, one of which is their molecular weight. Here, we address the question whether variations in the chain length and their distribution affect the degradation behavior of Poly[(rac-lactide)-co-glycolide]s (PDLLGA). The hydrolysis was studied in ultrathin films at the air-water interface in order to rule out any morphological effects. We found that both for purely hydrolytic degradation as well as under enzymatic catalysis, the molecular weight has very little effect on the overall degradation kinetics of PDLLGAs. The quantitative analysis suggested a random scission mechanism. The monolayer experiments showed that an acidic micro-pH does not accelerate the degradation of PDLLGAs, in contrast to alkaline conditions. The degradation experiments were combined with interfacial rheology measurements, which showed a drastic decrease of the viscosity at little mass loss. The extrapolated molecular weight behaved similar to the viscosity, dropping to a value near to the solubility limit of PDLLGA oligomers before mass loss set in. This observation suggests a solubility controlled degradation of PDLLGA. Conclusively, the molecular weight affects the degradation of PDLLGA devices mostly in indirect ways, e.g. by determining their morphology and porosity during fabrication. Our study demonstrates the relevance of the presented Langmuir degradation method for the design of controlled release systems.
18F-FDG Uptake of Localized Malignant Peritoneal Mesothelioma
Authors: Eriko Kodama, Toshiki Kodama, Tamaki Ichikawa, Haruka Ikoma, Jun Hashimoto
Journal: Clinical Nuclear Medicine (2019)

Abstract We present 2 cases of malignant peritoneal mesothelioma (MPM) characterized by a localized solid mass without ascites and showing 18 F-FDG uptake. A 79-year-old man with a history of asbestos exposure suffered from an epithelioid MPM originating from the hepatoduodenal ligament with FDG uptake (SUVmax 16.8). Another 80-year-old man with esophageal cancer showed desmoplastic MPM of the small bowel mesentery with FDG uptake (SUVmax 4.0). Desmoplastic MPM is more aggressive and yields poorer prognosis compared with the epithelioid type. However, the present desmoplastic MPM case showed mild FDG uptake because of rich fibrosis.
Oxidative stress-driven DR5 upregulation restores TRAIL/Apo2L sensitivity induced by iron oxide nanoparticles in colorectal cancer
Authors: Yesi Shi, Junqing Wang, Jingyi Liu, Gan Lin, Fengfei Xie, Xin Pang, Yihua Pei, Yi Cheng, Yang Zhang, Zhongning Lin, Zhengyu Yin, Xiaomin Wang, Gang Niu, Xiaoyuan Chen, Gang Liu
Journal: Biomaterials (2019)
PCSK6 Is a Key Protease in the Control of Smooth Muscle Cell Function in Vascular Remodeling
Authors: Urszula Rykaczewska, Bianca E. Suur, Samuel Röhl, Anton Razuvaev, Mariette Lengquist, Maria Sabater-Lleal, Sander W. van der Laan, Clint L. Miller, Robert C. Wirka, Malin Kronqvist, Maria Gonzalez Diez, Mattias Vesterlund, Peter Gillgren, Jacob Odeberg, Jan H. Lindeman, Fabrizio Veglia, Steve E. Humphries, Ulf de Faire, Damiano Baldassarre, Elena Tremoli, Janne Lehtiö, Göran K. Hansson, Gabrielle Paulsson-Berne, Gerard Pasterkamp, Thomas Quertermous, Anders Hamsten, Per Eriksson, Ulf Hedin, Ljubica Matic
Journal: Circulation Research (2020)

PCSKs (Proprotein convertase subtilisins/kexins) are a protease family with unknown functions in vasculature. Previously, we demonstrated PCSK6 upregulation in human atherosclerotic plaques associated with smooth muscle cells (SMCs), inflammation, extracellular matrix remodeling, and mitogens.Here, we applied a systems biology approach to gain deeper insights into the PCSK6 role in normal and diseased vessel wall.Genetic analyses revealed association of intronic PCSK6 variant rs1531817 with maximum internal carotid intima-media thickness progression in high-cardiovascular risk subjects. This variant was linked with PCSK6 mRNA expression in healthy aortas and plaques but also with overall plaque SMA+ cell content and pericyte fraction. Increased PCSK6 expression was found in several independent human cohorts comparing atherosclerotic lesions versus healthy arteries, using transcriptomic and proteomic datasets. By immunohistochemistry, PCSK6 was localized to fibrous cap SMA+ cells and neovessels in plaques. In human, rat, and mouse intimal hyperplasia, PCSK6 was expressed by proliferating SMA+ cells and upregulated after 5 days in rat carotid balloon injury model, with positive correlation to PDGFB (platelet-derived growth factor subunit B) and MMP (matrix metalloprotease) 2/MMP14. Here, PCSK6 was shown to colocalize and cointeract with MMP2/MMP14 by in situ proximity ligation assay. Microarrays of carotid arteries from Pcsk6-/- versus control mice revealed suppression of contractile SMC markers, extracellular matrix remodeling enzymes, and cytokines/receptors. Pcsk6-/- mice showed reduced intimal hyperplasia response upon carotid ligation in vivo, accompanied by decreased MMP14 activation and impaired SMC outgrowth from aortic rings ex vivo. PCSK6 silencing in human SMCs in vitro leads to downregulation of contractile markers and increase in MMP2 expression. Conversely, PCSK6 overexpression increased PDGFBB (platelet-derived growth factor BB)-induced cell proliferation and particularly migration.PCSK6 is a novel protease that induces SMC migration in response to PDGFB, mechanistically via modulation of contractile markers and MMP14 activation. This study establishes PCSK6 as a key regulator of SMC function in vascular remodeling. Visual Overview: An online visual overview is available for this article.
Adjudication rate as an indicator of read quality in clinical trials using progression-related endpoints assessed by imaging.
Authors: David Raunig, Gregory V. Goldmacher, James J Conklin
Journal: Journal of Clinical Oncology (2012)

e13082 Background: Progression-free survival determined by serial tumor burden assessments is a common oncology trial endpoint. Images are often assessed by two reviewers, with disagreement on progression date resolved by an adjudicator. Adjudication rate (AR) is a widely used metric of read quality, with AR &gt; 40% thought to indicate poor data. We examined factors that determine AR and the potential impact of overreliance upon it as a measure of data quality, using a statistical model of independent blinded review. Methods: Reads were simulated as a binary series of progression assessments with an underlying Gaussian decision process. Tumor burden increased in a linear fashion, with true progression at 21 weeks. Tumor measurement variability was constant, while visit frequency varied from 2 to 16 weeks. 1,000 runs of 100 patients were performed. For each run, AR and the variance and bias of time to progression were computed. Results: See table. Decreasing the visit interval relative to the progression rate increased AR but increased the accuracy and precision of the time to progression estimate. AR was less sensitive than other statistical tests of asymmetry for detection of reader bias. Conclusions: AR is affected by biological, image, and reader variability, progression rate, and visit interval. Frequent visits relative to progression increase AR, but lower bias and variance in time to progression estimates. High AR may occur even with strong readers, while very low AR may indicate loss of reader independence and data integrity. High ARs should be investigated to determine the effect on the progression endpoint. AR is not itself an endpoint, and is not a reliable indicator of read quality. Blindly attempting to minimize AR without understanding the cause may waste resources, divert attention from critical factors such as bias, and decrease a trial’s ability to detect differences between treatment arms. Other reader metrics, such as measures of asymmetrical disagreement, are recommended as alternative measures of read quality for oncology trials. [Table: see text]
18F-FET PET for Diagnosis of Pseudoprogression of Brain Metastases in Patients With Non–Small Cell Lung Cancer
Authors: Dilara Akhoundova, Stefanie Hiltbrunner, Cäcilia Mader, Robert Förster, Johannes Kraft, Bianca Schwanhäusser, Lorenz Bankel, Spyros Kollias, Valerie Treyer, Elisabeth Jane Rushing, Seok-Yun Lee, Nicolaus Andratschke, Martin Hüllner, Alessandra Curioni-Fontecedro
Journal: Clinical Nuclear Medicine (2019)

Purpose To evaluate whether 18 F-fluoroethyltyrosine (FET) PET can discriminate progression from pseudoprogression of brain metastases in patients with non–small cell lung cancer undergoing immunotherapy and radiotherapy to the brain. Methods Retrospective analysis of 18 F-FET PET scans in cases with documented progression of brain metastases on MRI in a cohort of 53 patients with non–small cell lung cancer receiving immune-checkpoint inhibitors and radiotherapy of brain metastases at the University Hospital of Zürich from June 2015 until January 2019. Response to radiotherapy was assessed by MRI. In case of equivocal findings and/or radiological progression in clinically asymptomatic patients, further assessment with 18 F-FET PET was performed. Results From the cohort of 53 patients, the restaging MRI showed in 30 patients (56.6%) progression of at least 1 treated metastasis. Thereof, 18 F-FET PET was performed in 11 patients, based on the absence of neurological symptoms or presence of systemic response and physicians' decision. 18 F-FET PET correctly identified pseudoprogression in 9 of 11 patients (81.8%). In patients who did not undergo 18 F-FET PET, 5 of 19 (26.3%) were diagnosed with pseudoprogression. Conclusions Pseudoprogression of brain metastases occurred in 50% of patients diagnosed with progression on MRI. 18 F-FET PET may help differentiate pseudoprogression from real progression in order to avoid discontinuation of effective therapy or unneeded interventions.
维生素 D 水平能否影响您的黑色素瘤风险?
Authors: U.E. Liyanage, M.H. Law, J.H. Barrett, M.M. Iles, S. MacGregor
Journal: British Journal of Dermatology (2020)

黑色素瘤是一种最致命的皮肤癌形式。根据澳大利亚癌症数据库统计数据, 2018 年, 黑色素瘤的发生率(意指病例数量)为 14778 例, 死亡人数为 1684 例。 在医学文献(如期刊)中关于维生素 D 可能对黑色素瘤风险发挥的作用存在很大争议。有些研究将维生素 D 缺乏症(意指维生素 D 水平较低)与许多不同癌症的风险增加相关联。 对黑色素瘤的研究充满困难, 这是因为虽然阳光中较高的紫外线辐射 (UVR) 水平使体内维生素 D 水平增加,但 UVR 暴露也会增加黑色素瘤的风险。 在本项目中, 作者旨在确定维生素 D 水平是否会影响黑色素瘤风险。他们进行了孟德尔随机化分析 (MR),这是一种分析不同基因变体的方法,其可用于确定因果关系(原因和效果)。这项研究使用了欧洲血统基因数据,并结合将遗传标志物与维生素 D 水平相关联的数据。 作者表明, 即使预测的维生素 D 水平变化很大(20 nmol/L 下降),也仅对黑色素瘤风险产生轻微影响。虽然有些研究表明, 改变维生素 D 水平可能会降低黑色素瘤风险, 但这项研究未提供证据证明, 基因确定的维生素 D 与黑色素瘤风险存在因果关系(相关联)。 This summary relates to the study: 维生素 D 与黑色素瘤风险之间是否存在因果关系?一项孟德尔随机化分析研究。
Patient and Disease–Specific Induced Pluripotent Stem Cells for Discovery of Personalized Cardiovascular Drugs and Therapeutics
Authors: David T. Paik, Mark Chandy, Joseph C. Wu
Journal: Pharmacological Reviews (2019)

Human induced pluripotent stem cells (iPSCs) have emerged as an effective platform for regenerative therapy, disease modeling, and drug discovery. iPSCs allow for the production of limitless supply of patient-specific somatic cells that enable advancement in cardiovascular precision medicine. Over the past decade, researchers have developed protocols to differentiate iPSCs to multiple cardiovascular lineages, as well as to enhance the maturity and functionality of these cells. Despite significant advances, drug therapy and discovery for cardiovascular disease have lagged behind other fields such as oncology. We speculate that this paucity of drug discovery is due to a previous lack of efficient, reproducible, and translational model systems. Notably, existing drug discovery and testing platforms rely on animal studies and clinical trials, but investigations in animal models have inherent limitations due to interspecies differences. Moreover, clinical trials are inherently flawed by assuming that all individuals with a disease will respond identically to a therapy, ignoring the genetic and epigenomic variations that define our individuality. With ever-improving differentiation and phenotyping methods, patient-specific iPSC-derived cardiovascular cells allow unprecedented opportunities to discover new drug targets and screen compounds for cardiovascular disease. Imbued with the genetic information of an individual, iPSCs will vastly improve our ability to test drugs efficiently, as well as tailor and titrate drug therapy for each patient.
More Explorations Needed on Association of Electronic Cigarette Use and Smoking Reduction
Authors: Danni He, Wenquan Niu
Journal: JAMA Internal Medicine (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 Internal Medicine 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 Internal Medicine journal
Nerve growth factor activates autophagy in Schwann cells to enhance myelin debris clearance and to expedite nerve regeneration
Authors: Rui Li, Duohui Li, Chengbiao Wu, Libing Ye, Yanqing Wu, Yuan Yuan, Shengnan Yang, Ling Xie, Yuqin Mao, Ting Jiang, Yiyang Li, Jian Wang, Hongyu Zhang, Xiaokun Li, Jian Xiao
Journal: Theranostics (2020)

Rationale: Autophagy in Schwann cells (SCs) is crucial for myelin debris degradation and clearance following peripheral nerve injury (PNI). Nerve growth factor (NGF) plays an important role in reconstructing peripheral nerve fibers and promoting axonal regeneration. However, it remains unclear if NGF effect in enhancing nerve regeneration is mediated through autophagic clearance of myelin debris in SCs. Methods: In vivo, free NGF solution plus with/without pharmacological inhibitors were administered to a rat sciatic nerve crush injury model. In vitro, the primary Schwann cells (SCs) and its cell line were cultured in normal medium containing NGF, their capable of swallowing or clearing degenerated myelin was evaluated through supplement of homogenized myelin fractions. Results: Administration of exogenous NGF could activate autophagy in dedifferentiated SCs, accelerate myelin debris clearance and phagocytosis, as well as promote axon and myelin regeneration at early stage of PNI. These NGF effects were effectively blocked by autophagy inhibitors. In addition, inhibition of the p75 kD neurotrophin receptor (p75NTR) signal or inactivation of the AMP-activated protein kinase (AMPK) also inhibited the NGF effect as well. Conclusions: NGF effect on promoting early nerve regeneration is closely associated with its accelerating autophagic clearance of myelin debris in SCs, which probably regulated by the p75NTR/AMPK/mTOR axis. Our studies thus provide strong support that NGF may serve as a powerful pharmacological therapy for peripheral nerve injuries.
Abstract 15660: Statin Use is Associated With Increased Overall Survival in Patients With Colorectal Cancer: Findings From a Cohort of 29,498 United States Veterans
Authors: Chiara Melloni, Gretchen G Kimmick, Taofik Oyekunle, Leah L Zullig, Michel G Khouri, Lauren Howard, Michael J Kelley, Susan F Dent
Journal: Circulation (2019)

Introduction: Statin use is associated with improved overall survival when used in the preventive setting and in some cancer populations, but data is lacking for colorectal cancer (CRC) patients. T...
The addition of a humidifier device to a circuit and its impact on home ventilator performance: a bench study
Authors: Javier Collada-Carrasco, Cristina Lamolda-Puyol, Manel Luján, Alba Castaño-Menéndez, Miguel Jiménez-Gómez, Ana Hernández-Voth, Javier Sayas-Catalán
Journal: Pulmonology (2019)

Humidification and non-invasive ventilation are frequently used together, despite the lack of precise recommendations regarding this practice. We aimed to analyse the impact of active external and built-in humidifiers on the performance of home ventilators, focusing on their pressurization efficacy and their behaviour under different inspiratory efforts. We designed a bench study of a lung simulator programmed to emulate mechanical conditions similar to those experienced by real respiratory patients and to simulate three different levels of inspiratory effort: five different commonly used home NIV devices and active humidifiers attached to the latter (internal or "built-in") or to the circuit (external). To test ventilator pressurization under different humidification and effort settings, pressure-time products in the first 300 ms and 500 ms of the respiratory cycle were calculated in the 45 situations simulated. Inferential statistical analysis was performed. A significant reduction of PTP 300 and PTP 500 was observed with the external humidifier in three of the devices. The same pattern was noted for another device with an internal humidifier, and only one device showed no significant changes. This impact on pressurization was commonly higher under high inspiratory effort. These results indicate the need to monitor pressure changes in the use of external humidification devices in some home NIV ventilators.
HPV16 drives cancer immune escape via NLRX1-mediated degradation of STING
Authors: Xiaobo Luo, Christopher R. Donnelly, Wang Gong, Blake R. Heath, Yuning Hao, Lorenza A. Donnelly, Toktam Moghbeli, Yee Sun Tan, Xin Lin, Emily Bellile, Benjamin A. Kansy, Thomas E. Carey, J. Chad Brenner, Lei Cheng, Peter J. Polverini, Meredith A. Morgan, Haitao Wen, Mark E. Prince, Robert L. Ferris, Yuying Xie, Simon Young, Gregory T. Wolf, Qianming Chen, Yu L. Lei
Journal: Journal of Clinical Investigation (2019)

The incidence of human papillomavirus–positive (HPV+) head and neck squamous cell carcinoma (HNSCC) has surpassed that of cervical cancer and is projected to increase rapidly until 2060. The coevolution of HPV with transforming epithelial cells leads to the shutdown of host immune detection. Targeting proximal viral nucleic acid–sensing machinery is an evolutionarily conserved strategy among viruses to enable immune evasion. However, E7 from the dominant HPV subtype 16 in HNSCC shares low homology with HPV18 E7, which was shown to inhibit the STING DNA-sensing pathway. The mechanisms by which HPV16 suppresses STING remain unknown. Recently, we characterized the role of the STING/type I interferon (IFN-I) pathway in maintaining immunogenicity of HNSCC in mouse models. Here we extended those findings into the clinical domain using tissue microarrays and machine learning–enhanced profiling of STING signatures with immune subsets. We additionally showed that HPV16 E7 uses mechanisms distinct from those used by HPV18 E7 to antagonize the STING pathway. We identified NLRX1 as a critical intermediary partner to facilitate HPV16 E7–potentiated STING turnover. The depletion of NLRX1 resulted in significantly improved IFN-I–dependent T cell infiltration profiles and tumor control. Overall, we discovered a unique HPV16 viral strategy to thwart host innate immune detection that can be further exploited to restore cancer immunogenicity.
A randomized, placebo-controlled trial of emricasan in patients with NASH and F1-F3 fibrosis
Authors: Stephen A. Harrison, Zachary Goodman, Abdul Jabbar, Ravi Vemulapalli, Ziad H. Younes, Bradley Freilich, Muhammad Y. Sheikh, Jörn M. Schattenberg, Zeid Kayali, Adam Zivony, Aasim Sheikh, Javier Garcia-Samaniego, Sanjaya K. Satapathy, George Therapondos, Edward Mena, Detlef Schuppan, James Robinson, Jean L. Chan, David T. Hagerty, Arun J. Sanyal
Journal: Journal of Hepatology (2019)
Quality and Safety in Healthcare, Part LIX
Authors: Jay A. Harolds
Journal: Clinical Nuclear Medicine (2019)

Abstract Decreasing the physician workload by promoting processes that produce greater efficiency, including the use of teams and delegating certain jobs to nurses, advanced practice providers, and scribes, is very helpful to reduce burnout and promote wellness. The team approach and enlightened leadership at all levels are important to maximize productivity, have common goals doing meaningful work, and have more control over the environment at work, all of which also results in less burnout and greater wellness.