tbuckley/cabot-search huggingface dataset:
CMET-07. TUMOR RELATED IMPAIRMENTS OF NEUROCOGNITIVE FUNCTIONS IN PATIENTS WITH BRAIN METASTASES
Authors: Junjie Zhen, Shaoqun Li, Zhangrui Peng, Lei Wen, Mingyao Lai, Linbo Cai
Journal: Neuro-Oncology (2019)

Abstract OBJECTIVE To study whether the neurocognitive functions were affected by brain metastases in patients, and what are the potential risk factors. METHODS A total of 172 patients with brain metastases were retrospectively analyzed. Prior to radiotherapy of brain metastases, the neurocognitive functions were evaluated by a wide range of tests including MOCA, VFT, HVLT-R, TMT-A, TMT-B and TOL. Kappa test was used to analyze the consistency of physical examination and neurocognitive assessment results. The related factors were analyzed with univariate and multivariate analysis. RESULTS 53 out of 172 patients (30.8%) were identified with cognitive impairments by physical examination. The assessment with neurocognitive scales revealed that there were 148 cases of cognitive impairment (86.0%) and 24 cases of normal cognition (14.0%). Kappa=0.025, indicating that the difference between neurocognitive assessment results and physical examination was significant. The univariate analysis on the factors related to neurocognitive impairment revealed that the risk factors that may affect the neurocognitive functions included age, KPS, m-GPA score, RPA classification, whether the original tumor was under control, with or without brain metastases. After adjusting for education, the multivariate analysis showed that age≥45 years old, KPS≤70, RPA classification &amp;gt;2 and m-GPA score&amp;lt; 3 were independent risk factors for neurocognitive impairment. CONCLUSION Patients with brain metastases were found to have various degrees of neurocognitive impairment prior to radiotherapy. The neurocognitive functions of patients can be more precisely evaluated by a comprehensive scale assessment. Age, KPS, RPA classification and m-GPA score are the main factors associated with neurocognitive impairment.
MANAGEMENT, OUTCOMES AND SURVIVAL OF AN AUSTRALIAN IgG4-SCLEROSING CHOLANGITIS COHORT: THE MOSAIC STUDY
Authors: William W Kemp, Ammar Majeed, Avik Majumdar, Edmund Tse, Richard Skoien, Daniel Croagh, Anouk Dev, Hugh Gao, Martin Weltman, Philip I Craig, Katherine Stuart, Wendy Cheng, Simon Edmunds, Eric Lee, Siddharth Sood, Andrew Metz, Abhimati Ravikulan, Alexander J Thompson, Marie Sinclair, Lauren Beswick, Amanda J Nicoll, Stephen Riordan, Alicia Braund, Kate Muller, Stuart K Roberts, Jo Mitchell
Journal: Hepatology (2019)
How Is Money Changing Medicine?—Venture Capital Investment in Oncology
Authors: Kevin B. Huang, Vinod E. Nambudiri
Journal: JAMA Oncology (2020)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Oncology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Oncology journal
Abstract 256: Active Compression Decompression CPR With 5 Centimeters Lift and an Impedance Threshold Device Significantly Improves All Markers of Cerebral and Cardiovascular Hemodynamics and Blood Flow After 8 Minutes of Standard CPR
Authors: Michael Lick, Paul S Berger, Jeff R Gould, Anja Metzger
Journal: Circulation (2019)

Introduction: Active compression decompression (ACD) CPR performed along with the use of an impedance threshold device (ITD) has been shown to improve cerebral and coronary hemodynamics compared to standard CPR (SCPR). In this study, we demonstrate that ACD+ITD provides significant benefits even when initiated after 8 minutes of SCPR as measured by cerebral and cardiovascular perfusion pressures, cerebral oximetry, and blood flow as determined by neutron-activated microsphere analysis. Methods: Ventricular fibrillation was induced in 10 female Yorkshire farm pigs (40.6 ± 0.7 kg) and left untreated for 6 minutes. All animals then received 8 minutes of SCPR, followed by ACD+ITD for an additional 6 minutes. CPR was performed at a rate of 100 compressions/minute at a depth of 20% (~ 5 cm) of anteroposterior chest height. During ACD there was also an active lift component of 5cm beyond resting chest position. Microspheres were injected 4 minutes after starting SCPR and 2 minutes after starting ACD+ITD. Millar catheters were placed to measure right atrial, aortic, and intracranial pressures and NIRS was used to assess regional cerebral oxygenation. 3 minute averages obtained prior to the end of each intervention were compared with Student’s t-test and reported as mean ± SEM. Results: Mean coronary perfusion pressure and cerebral perfusion pressures were significantly improved during ACD+ITD (p&lt;0.002, Fig 1). ACD+ITD also resulted in a 7% increase in cerebral oxygenation (47 ± 2 vs 50 ± 2%, p&lt;0.001), a 30% increase in cerebral blood flow (0.3 ± 0.1 vs 0.4 ± 0.1ml/min/gm, p&lt;0.004), and a 30% improvement in coronary blood flow (0.6 ± 0.1 vs. 0.9 ± 0.1ml/min/gm, p&lt;0.004). Conclusion: This study reveals the significant benefit of ACD+ITD as measured by currently available invasive and non-invasive blood flow measurements following 8 minutes of SCPR. Initiating ACD+ITD earlier can only result in further improvement of these parameters and offer a higher likelihood of survival.
The role of anxiety in the integrative memory model
Authors: Benjamin C. Nephew, Serhiy Chumachenko, Brent P. Forester
Journal: Behavioral and Brain Sciences (2019)

Abstract We suggest that the inclusion of anxiety, as one relevant mood factor, could enhance the implementation of the integrative memory model in research and the clinic. The role of anxiety in Alzheimer's disease neuroanatomy, symptomology, and progression is used as an example. Customization of the integrative memory model can establish strong foundations for pathology-specific models of memory deficits, enhancing the development of precision medicine applications.
Catalase-based liposomal for reversing immunosuppressive tumor microenvironment and enhanced cancer chemo-photodynamic therapy
Authors: Chao Shi, Mingle Li, Zhen Zhang, Qichao Yao, Kun Shao, Feng Xu, Ning Xu, Haidong Li, Jiangli Fan, Wen Sun, Jianjun Du, Saran Long, Jingyun Wang, Xiaojun Peng
Journal: Biomaterials (2020)
Novel ultrasonographic Halo Score for giant cell arteritis: assessment of diagnostic accuracy and association with ocular ischaemia
Authors: Kornelis S M van der Geest, Frances Borg, Abdul Kayani, Davy Paap, Prisca Gondo, Wolfgang Schmidt, Raashid Ahmed Luqmani, Bhaskar Dasgupta
Journal: Annals of the Rheumatic Diseases (2020)

Objectives Ultrasound of temporal and axillary arteries may reveal vessel wall inflammation in patients with giant cell arteritis (GCA). We developed a ultrasound scoring system to quantify the extent of vascular inflammation and investigated its diagnostic accuracy and association with clinical factors in GCA. Methods This is a prospective study including 89 patients suspected of having GCA, of whom 58 had a confirmed clinical diagnosis of GCA after 6 months follow-up. All patients underwent bilateral ultrasound examination of the three temporal artery (TA) segments and axillary arteries, prior to TA biopsy. The extent of vascular inflammation was quantified by (1) counting the number of TA segments and axillary arteries with a halo and (2) calculating a composite Halo Score that also incorporated the thickness of each halo. Results Halo counts and Halo Scores showed moderate diagnostic accuracy for a clinical diagnosis of GCA. They correlated positively with systemic inflammation. When compared with the halo count, the Halo Score correlated better with C-reactive protein (CRP) levels and allowed to firmly establish the diagnosis of GCA in more patients. Higher halo counts and Halo Scores were associated with a higher risk of ocular ischaemia. They allowed to identify subgroups of patients with low risk (≤5%) and high risk of ocular ischaemia (&gt;30%). Conclusions Ultrasound halo scoring allows to quantify the extent of vascular inflammation in GCA. Extensive vascular inflammation on ultrasound may provide strong diagnostic confirmation and associates with ocular ischaemia in GCA.
Critical Role of Cytosolic DNA and Its Sensing Adaptor STING in Aortic Degeneration, Dissection, and Rupture
Authors: Wei Luo, Yidan Wang, Lin Zhang, Pingping Ren, Chen Zhang, Yanming Li, Alon R. Azares, Michelle Zhang, Jiao Guo, Ketan B. Ghaghada, Zbigniew A. Starosolski, Kimal Rajapakshe, Cristian Coarfa, Yumei Li, Rui Chen, Keigi Fujiwara, Jun-ichi Abe, Joseph S. Coselli, Dianna M. Milewicz, Scott A. LeMaire, Ying H. Shen
Journal: Circulation (2019)

Background: Sporadic aortic aneurysm and dissection (AAD), caused by progressive aortic smooth muscle cell (SMC) loss and extracellular matrix degradation, is a highly lethal condition. Identifying mechanisms that drive aortic degeneration is a crucial step in developing an effective pharmacologic treatment to prevent disease progression. Recent evidence has indicated that cytosolic DNA and abnormal activation of the cytosolic DNA sensing adaptor STING (stimulator of interferon genes) play a critical role in vascular inflammation and destruction. Here, we examined the involvement of this mechanism in aortic degeneration and sporadic AAD formation. Methods: The presence of cytosolic DNA in aortic cells and activation of the STING pathway were examined in aortic tissues from patients with sporadic ascending thoracic AAD. The role of STING in AAD development was evaluated in Sting -deficient ( Sting gt/gt ) mice in a sporadic AAD model induced by challenging mice with a combination of a high-fat diet and angiotensin II. We also examined the direct effects of STING on SMC death and macrophage activation in vitro. Results: In human sporadic AAD tissues, we observed the presence of cytosolic DNA in SMCs and macrophages and significant activation of the STING pathway. In the sporadic AAD model, Sting gt/gt mice showed significant reductions in challenge-induced aortic enlargement, dissection, and rupture in both the thoracic and abdominal aortic regions. Single-cell transcriptome analysis revealed that aortic challenge in wild-type mice induced the DNA damage response, the inflammatory response, dedifferentiation and cell death in SMCs, and matrix metalloproteinase expression in macrophages. These changes were attenuated in challenged Sting gt/gt mice. Mechanistically, nuclear and mitochondrial DNA damage in SMCs and the subsequent leak of DNA to the cytosol activated STING signaling, which induced cell death through apoptosis and necroptosis. In addition, DNA from damaged SMCs was engulfed by macrophages in which it activated STING and its target interferon regulatory factor 3, which directly induced matrix metalloproteinase-9 expression. We also found that pharmacologically inhibiting STING activation partially prevented AAD development. Conclusions: Our findings indicate that the presence of cytosolic DNA and subsequent activation of cytosolic DNA sensing adaptor STING signaling represent a key mechanism in aortic degeneration and that targeting STING may prevent sporadic AAD development.
Exhaled nitric oxide in a model of chronic airway inflammation in guiena pigs: modulation by montelukast sodium and dexamethasone treatment
Authors: F. T. Fernandes, F. U. Kay, E. A. Maldonado-Leick, C. M. Prado, D. J. Kasahara, C. H. Abib, A. S. Leme, Mílton de Arruda Martins, I. F. L. C. Tiberio
Journal: American Journal of Respiratory and Critical Care Medicine (2002)
Prognostic significance of KRAS and BRAF mutations in Japanese patients with colorectal cancer.
Authors: Eiji Oki, Ryota Nakanishi, Koji Ando, Hiroshi Saeki, Takefumi Ohga, Yoshihiro Kakeji, Shunichi Tsujitani, Shunji Kohnoe, Yoshihiko Maehara
Journal: Journal of Clinical Oncology (2012)

e14033 Background: Recent evidence highlights the potential prognostic and predictive value of BRAF and K-RAS gene alterations in patients with colorectal cancer. To determine whether differences exist in the molecular mechanisms driving colorectal cancer between Japanese and Western, we characterized Japanese patients with colorectal cancer by assessing genetic alterations involved in cancer progression and response to treatment. Methods: We retrospectively evaluated 254 Japanese diagnosed with colorectal cancer at our institution between 1994 and 2009. Mutations in KRAS codons 12 and 13 and BRAF codon 600 were identified by direct sequencing. Microsatellite instability (MSI) status was determined by genotyping in the 5 loci. Associations between KRAS or BRAF mutation and clinicopathological characteristics and prognosis were evaluated. Results: KRAS and BRAF mutation were detected in 33.5% and 6.7% of all patients, respectively. KRAS mutation was correlated with poor recurrence free survival (RFS) (p = 0.03), especially in stage II patients (p = 0.007). BRAF mutation was significantly correlated with the anatomical site of tumor (p &lt; 0.001), tumor grade (p = 0.001) and high frequency of microsatellite instability (p &lt; 0.001). BRAF mutation was also correlated with poor overall survival in all cases of patients (p = 0.009). Overall, the background of KRAS and BRAF mutation was almost similar between CRCs of Western countries and those of Japanese. However, KRAS mutation status was considered to be helpful to predict recurrence in Japanese patients with stage II CRC. Conclusions: Our findings indicate that BRAF and K-RAS mutation plays an important role in the tumorigenesis of colorectal cancer. These results indicate that molecular analysis for BRAF and K-RAS may be a useful biomarker for identifying patients with right-sided colon cancer with poor outcome who may benefit from a more individualized course of therapy.
Innate immune priming in the absence of TAK1 drives RIPK1 kinase activity–independent pyroptosis, apoptosis, necroptosis, and inflammatory disease
Authors: R.K. Subbarao Malireddi, Prajwal Gurung, Sannula Kesavardhana, Parimal Samir, Amanda Burton, Harisankeerth Mummareddy, Peter Vogel, Stephane Pelletier, Sandeepta Burgula, Thirumala-Devi Kanneganti
Journal: The Journal of Experimental Medicine (2019)

RIPK1 kinase activity has been shown to be essential to driving pyroptosis, apoptosis, and necroptosis. However, here we show a kinase activity–independent role for RIPK1 in these processes using a model of TLR priming in a TAK1-deficient setting to mimic pathogen-induced priming and inhibition. TLR priming of TAK1-deficient macrophages triggered inflammasome activation, including the activation of caspase-8 and gasdermin D, and the recruitment of NLRP3 and ASC into a novel RIPK1 kinase activity–independent cell death complex to drive pyroptosis and apoptosis. Furthermore, we found fully functional RIPK1 kinase activity–independent necroptosis driven by the RIPK3–MLKL pathway in TAK1-deficient macrophages. In vivo, TAK1 inactivation resulted in RIPK3–caspase-8 signaling axis–driven myeloid proliferation and a severe sepsis-like syndrome. Overall, our study highlights a previously unknown mechanism for RIPK1 kinase activity–independent inflammasome activation and pyroptosis, apoptosis, and necroptosis (PANoptosis) that could be targeted for treatment of TAK1-associated myeloid proliferation and sepsis.
Solitary Cerebellar Metastasis of Ovarian Cancer Detected by FDG PET/CT
Authors: Guozhu Hou, Yuanyuan Jiang, Xin Cheng
Journal: Clinical Nuclear Medicine (2019)

Abstract Ovarian cancer with solitary metastasis to the cerebellum is very rare. We presented a 58-year-old woman complaining of headaches 9 months after debulking surgery and chemotherapy due to ovarian cancer. The serum CA125 level was elevated. FDG PET/CT was then recommended to identify potential malignancy and showed a hypermetabolic mass in the right cerebellum. The cerebellar mass was surgically removed, and the pathology confirmed metastasis from ovarian cancer.
Patients with schizophrenia and breast cancer: Adjuvant radiation treatment.
Authors: Lauren Davies, Kashif Abdullah, Radhakrishna Janardhan, Mark Hwang, Michael Farasatpour, Julie A. Margenthaler, Katherine S. Virgo, Frank E. Johnson
Journal: Journal of Clinical Oncology (2013)

e17506 Background: Schizophrenia affects about 1% of subjects in all populations studied so far. It impairs medical care delivery. We sought to evaluate how patients with schizophrenia who are later diagnosed with breast carcinoma fare when adjuvant radiation therapy (ART) is indicated. Methods: We searched the Patient Treatment File (PTF) of the Department of Veterans Affairs (DVA) to identify subjects with schizophrenia who later developed breast carcinoma and were treated in DVA Medical Centers (DVAMCs) from 1999 - 2005. Chart-based clinical data from the DVAMCs where the subjects had been treated supplemented PTF data. Results: 42 patients had preexisting schizophrenia, later developed breast carcinoma, and were candidates for ART. There were 31 women (74%) and 11 men (26%). 27 of the 42 study subjects had records specifying TNM stage; 18 of the 27 (67%) had TNM stages III-IV. 31 subjects had records about compliance with indicated medical therapies; 24 (77%) had previously been non-compliant. 39 subjects had records regarding therapy delay; 20 (51%) had previously delayed medically indicated therapy. Of the 42 subjects who were candidates for ART based on TNM stage, we found data about the decision to recommend ART in 37; only 23 (26%) were offered ART and 3 of those 23 (26%) refused it. Of the 6 subjects who refused ART, 4 had been non-compliant with previous medically indicated care, 3 had delayed initial cancer treatment, 4 had documented suicidal ideation, and 2 had documented homicidal ideation before being offered ART. Conclusions: Subjects with schizophrenia and breast carcinoma often do not understand their illnesses well. They often do not comply with recommended standard therapies such as ART. Treatments that rely on ART are likely to be met with non-compliance. A history of non-compliance appears to be a predictor of non-compliance with ART. Our results should be of interest to caregivers because we describe ways to avoid suboptimal ART in patients with breast carcinoma. Breast-conserving multi-modality treatment with ART is frequently not appropriate; radical surgery is often preferable.
Association of Intrinsic Brain Architecture With Changes in Attentional and Mood Symptoms During Development
Authors: Susan Whitfield-Gabrieli, Carter Wendelken, Alfonso Nieto-Castañón, Stephen Kent Bailey, Sheeba Arnold Anteraper, Yoon Ji Lee, Xiao-qian Chai, Dina R. Hirshfeld-Becker, Joseph Biederman, Laurie E. Cutting, Silvia A. Bunge
Journal: JAMA Psychiatry (2019)

Understanding the neurodevelopmental trajectory of psychiatric symptoms is important for improving early identification, intervention, and prevention of mental disorders.
A Phase I Study of ASTX660, an Antagonist of Inhibitors of Apoptosis Proteins, in Adults with Advanced Cancers or Lymphoma
Authors: Monica M. Mita, Patricia M. LoRusso, Kyriakos P. Papadopoulos, Michael S. Gordon, Alain C. Mita, Roberta Ferraldeschi, Harold Keer, Aram Oganesian, Xiang Yao Su, Simone Jueliger, Anthony W. Tolcher
Journal: Clinical Cancer Research (2020)

Abstract Purpose: This first-in-human, phase I study evaluated ASTX660, an oral, small-molecule antagonist of cellular/X-linked inhibitors of apoptosis proteins in patients with advanced solid tumors or lymphoma. Patients and Methods: ASTX660 was administered orally once daily on a 7-day-on/7-day-off schedule in a 28-day cycle. Dose escalation followed a standard 3+3 design to determine the MTD and recommended phase II dose (RP2D). Dose expansion was conducted at the RP2D. Results: Forty-five patients received ASTX660 (range 15–270 mg/day). Dose-limiting toxicity of grade 3 increased lipase with or without increased amylase occurred in 3 patients at 270 mg/day and 1 patient at 210 mg/day. The MTD was determined to be 210 mg/day and the RP2D 180 mg/day. Common treatment-related adverse events included fatigue (33%), vomiting (31%), and nausea (27%). Grade ≥3 treatment-related adverse events occurred in 7 patients, most commonly anemia (13%), increased lipase (11%), and lymphopenia (9%). ASTX660 was rapidly absorbed, with maximum concentration achieved at approximately 0.5–1.0 hour. An approximately 2-fold accumulation in AUC exposures was observed on day 7 versus 1. ASTX660 suppressed cellular inhibitor of apoptosis protein-1 in peripheral blood mononuclear cells, which was maintained into the second cycle beyond the off-therapy week at the 180-mg/day RP2D and above. Clinical activity was seen in a patient with cutaneous T-cell lymphoma. Conclusions: ASTX660 demonstrated a manageable safety profile and exhibited evidence of pharmacodynamic and preliminary clinical activity at the 180-mg/day RP2D. The phase II part of the study is ongoing.
Pragmatic Clinical Trial-Collateral Findings: Recognizing the Needs of Low-Resource Research Participants
Authors: Courtney A. Stewart, Kayla E. Cooper, Megan B. Raymond, Faith E. Fletcher, Vence L. Bonham
Journal: The American Journal of Bioethics (2020)

Courtney A. Stewarta, Kayla E. Coopera, Megan B. Raymondb, Faith E. Fletcherc & Vence L. Bonhama*a National Human Genome Research Institute; b University of Pittsburgh School of Medicine; c Department of Health Behavior, University of Alabama at Birmingham School of Public Health