tbuckley/cabot-search huggingface dataset:
Weekly dosing of the investigational oral proteasome inhibitor MLN9708 in patients (pts) with relapsed/refractory multiple myeloma (MM): A phase I study.
Authors: Shaji Kumar, William Bensinger, Craig B. Reeder, Todd M. Zimmerman, James R. Berenson, Guohui Liu, Deborah Berg, Neeraj Gupta, Alessandra Di Bacco, Ai-Min Hui, Ruben Niesvizky
Journal: Journal of Clinical Oncology (2012)

8034 Background: Phase 1 studies are evaluating IV and oral dosing of the reversible proteasome inhibitor MLN9708 in multiple tumor types. We report the safety, MTD, pharmacokinetics (PK), pharmacodynamics, and preliminary responses with weekly oral MLN9708 in pts with relapsed/refractory MM (NCT00963820). Methods: Pts aged ≥18 yrs received MLN9708 on d 1, 8, and 15 of 28-d cycles. In the dose-escalation phase, pts required ≥2 prior therapies (including bortezomib, thalidomide/lenalidomide, and corticosteroids). At the MTD, pts were to be enrolled to relapsed and refractory (RR), bortezomib-relapsed (VR), proteasome inhibitor (PI) naïve, and carfilzomib (CZ) expansion cohorts. Results: 36 pts have been enrolled to date (data cut-off: Dec 1, 2011), 32 in the dose-escalation phase (0.24–3.95 mg/m 2 ) and 8 to expansion cohorts (2 RR, 5 VR, 1 PI naïve; RR and VR cohorts each include 2 pts from MTD dose-escalation cohort). Median age was 64.5 yrs (range 40–79), 53% were male, and median number of prior lines of therapy was 3.5 (range 1-13), including 92%, 92%, 56%, and 8% who had prior bortezomib, lenalidomide, thalidomide, and carfilzomib, respectively. Pts have received a median of 2 cycles (range 1–11); 5 pts remain on treatment. Among 24 DLT-evaluable pts, 3 DLTs were seen: 2 at 3.95 mg/m 2 (1 grade 3 rash, 1 grade 3 GI AEs) and 1 at 2.97 mg/m 2 (grade 3 GI AEs). The MTD was determined as 2.97 mg/m 2 . Overall, 69% of pts had drug-related AEs, and 28% had related grade ≥3 AEs, including thrombocytopenia (17%), diarrhea (11%), nausea, neutropenia, and fatigue (each 8%). Only 3 (8%) pts had drug-related peripheral neuropathy (PN; no grade ≥3). 2 pts discontinued due to AEs. In 18 response-evaluable pts, 1 had a VGPR at 3.95 mg/m 2 , 1 had a PR at 2.97 mg/m 2 , and 8 have achieved SD durable for up to 9.5 mos. PK analyses showed linear plasma PK (0.8–3.95 mg/m 2 ), T max of 0.5-2 hr, and terminal half-life of 7 d for MLN2238 (biologically active hydrolysis product). There was a trend for a dose-dependent increase in whole blood 20S proteasome inhibition. Conclusions: Current data suggest weekly oral MLN9708 is generally well tolerated with infrequent PN, and shows early signs of antitumor activity.
Abstract 15502: Thrombus Aspiration in Primary Percutaneous Coronary Intervention: An Updated Meta-analysis
Authors: João Carmo, Francisco M Costa, Jorge Ferreira, Miguel Mendes
Journal: Circulation (2015)

Background: During primary percutaneous coronary intervention (PPCI), routine thrombus aspiration has been proposed based on small trials that suggested improved clinical outcomes, but last trials had reported conflicting results. We aimed to access whether thrombus aspiration and PPCI is superior to PPCI alone on clinical outcomes in patients with ST-elevation myocardial infarction, based on last clinical data. Methods: PubMed, Embase and Cochrane databases were searched. We included studies that randomized patients with ST-elevation myocardial infarction to thrombus aspiration and PPCI versus PPCI alone, and excluded studies that did not have clinical outcomes and those in which mechanical thrombectomy was used. We calculated risk ratio with 95% confidence interval (CI) for all-cause mortality, reinfarction, target vessel revascularization, stent thrombosis and stroke. Results: Twenty randomized trials enrolling 21,368 patients were included. Of these, 10,661 were randomized to thrombus aspiration and PPCI, and the remaining 10,707 to PPCI only. The all-cause mortality was similar between the two groups (risk ratio [RR] = 0.88; 95% CI 0.77-1.01, p=0.07). Although reinfarction (RR = 0.96; 0.80-1.15, p=0.64), target vessel revascularization (RR 0.93; 0.83-1.07; p=0.26) and stent thrombosis (RR = 0.83; 0.65-1.07, p=0.15) were also similar between the two groups, there was an increase in rate of stroke in patients randomized to thrombus aspiration (RR = 1.52; 1.08-2.14; p=0.02). Conclusion: This meta-analysis that includes the largest trial to date showed that thrombus aspiration did not reduce mortality, reinfarction, target vessel revascularization or stent thrombosis, but was associated with a higher rate of stroke.
CD97 Promotes Tumor Aggressiveness Through the Traditional G Protein–Coupled Receptor–Mediated Signaling in Hepatocellular Carcinoma
Authors: Yin Yin, Xiaoliang Xu, Junwei Tang, Wenjie Zhang, Guangyan Zhangyuan, Jie Ji, Lei Deng, Shuai Lu, Han Zhuo, Beicheng Sun
Journal: Hepatology (2018)

Cluster of differentiation 97 (CD97) is a member of the epidermal growth factor seven-transmembrane family belonging to the class B G protein-coupled receptors (GPCRs). The protein affects tumor aggressiveness through its cellular ligand CD55 stimulation and exhibits adhesive properties. Studies have demonstrated the involvement of CD97 in dedifferentiation, migration, invasiveness, and metastasis of tumors. However, little information is currently available on the specific role of CD97 in hepatocellular carcinoma (HCC). Here, we have shown that CD97 up-regulation in HCCs is positively correlated with tumor metastasis. Functionally, CD97 promoted cell migration and invasion in vitro. In an in vivo mouse model, overexpression of CD97 in HCC cells led to accelerated lung metastasis. Mechanistically, CD97 cooperated with the altered regulator, GPCR kinase 6 (GRK6), to mediate GPCR desensitization and internalization. Down-regulation of GRK6 suppressed CD97 internalization and promoted CD97 expression. Integrated regulatory interactions between CD97 and GRK6 stimulated downstream matrix metalloproteinase 2/9 secretion and, consequently, HCC metastasis. Conclusion: Our collective findings support the utility of CD97 as an effective potential prognosticator and therapeutic target for HCC.
Donor-specific anti-HLA antibodies are not associated with non-anastomotic biliary strictures, but both are independent risk factors for graft loss after liver transplantation
Authors: A.C. den Dulk, X. Shi, C. Verhoeven, J. Dubbeld, F.H.J. Claas, R. Wolterbeek, S. Brand-Schaaf, H.W. Verspaget, A.F. Sarasqueta, L. van der Laan, H. Metselaar, B. van Hoek, J. Kwekkeboom, D. Roelen
Journal: Journal of Hepatology (2018)
Behavioral Phenotyping in Health Promotion
Authors: Shreya Kangovi, David A. Asch
Journal: JAMA (2018)

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 Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Abstract 15170: Persistent Microvascular Obstruction Leads to Localized Iron Deposition and Active Inflammation Within Chronic Myocardial Infarctions
Authors: Avinash Kali, Ivan Cokic, Hsin-Jung Yang, Richard Tang, Rohan Dharmakumar
Journal: Circulation (2015)

Introduction: The mechanism by which persistent microvascular obstruction (PMO) post myocardial infarction (MI) exerts adverse long-term effects is not well understood. Hypothesis: We hypothesized that PMO, with or without reperfusion hemorrhage, can resolve into iron deposition within chronic MI (CMI) territories, and is associated with prolonged inflammation and adverse LV remodeling. Methods: Canines subjected to reperfused (n=17) and non-reperfused (n=16) MI underwent Cardiovascular Magnetic Resonance (CMR) at 7 (acute) and 56 days (chronic) post-MI. Cine, T2*-weighted and Late Gadolinium Enhancement images were used to characterize LV remodeling (End-Diastolic Sphericity Index (EDSI)), iron and PMO respectively. Histological analysis was used to examine chronic inflammation. Results: In the reperfused group, 9 canines had PMO and hemorrhage with subsequent chronic iron deposition (PMO+/T2*+), while 4 canines had no PMO, hemorrhage, or chronic iron deposition (PMO-/T2*-). The remaining 4 canines had PMO without hemorrhage (PMO+/T2*-), but all subsequently had chronic iron deposition. In the non-reperfused group, 15 canines had PMO, and acute and subsequent chronic iron deposition (NR-PMO+/T2*+); 1 canine had no PMO, acute or chronic iron deposition (NR-PMO-/T2*-). In both groups, PMO volume was significantly associated with both acute and chronic iron volumes (p&lt;0.001 all cases). In both groups, infarct and iron volumes measured in both acute and chronic phases were significant predictors of change in EDSI between acute and chronic phases (p&lt;0.01 all cases). Histological sections of the harvested hearts post day 56 CMR showed extensive newly recruited macrophage, IL-1β, TNF-α and MMP-9 activities highly localized with iron in CMI regions (p&lt;0.001 all cases). Conclusions: PMO, with or without reperfusion hemorrhage, can lead to iron deposition within CMIs, and is associated with active inflammation and adverse LV remodeling in canines.
Cognitive technology addressing optimal cancer clinical trial matching and protocol feasibility in a community cancer practice.
Authors: J. Thaddeus Beck, Michael Vinegra, Irene Dankwa-Mullan, Adam Torres, Courtney C Simmons, Helen Holtzen, Alexandra Urman, Nancy Roper, Andrew D Norden, Melissa Rammage, Steven Hancock, Kyungae Lim, Prasanna Rao, Sadie Coverdill, Louisa Roberts, Paul Williamson, Mickey Howell, Quincy Chau, Kenneth W. Culver, Robert William Sweetman
Journal: Journal of Clinical Oncology (2017)

6501 Background: IBM Watson for Clinical Trial Matching (CTM) is a cognitive computing solution that uses natural language processing (NLP) to help increase the efficiency and accuracy of the clinical trial matching process. This solution helps providers locate suitable protocols for their patients by reading the trial criteria and matching it to the structured and unstructured patient characteristics when integrated with the Electronic Medical Record (EMR). It is also designed to determine which sites have the most viable patient population and identify inclusion and exclusion criteria that limit enrollment. Methods: This project was a collaboration among Highlands Oncology Group (HOG), Novartis and IBM Watson Health to explore the use of CTM in a community oncology practice. HOG is in Northeast Arkansas and has 15 physicians and 310 staff members working across 3 sites. During the 16-week pilot period, data from 2,620 visits by lung and breast cancer patients were processed by the CTM system. Using NLP capabilities, CTM read the clinical trial protocols provided by Novartis, and evaluated the patient data against the protocols’ inclusion and exclusion criteria. Watson excluded ineligible patients, determined those that needed further screening, and assisted in that process. Feedback on the user experience was also obtained. Results: In an initial pre-screening test, the HOG clinical trial coordinator (CTC) took 1 hour and 50 minutes to process 90 patients against 3 breast cancer protocols. Conversely, when the CTM screening solution was used, it took 24 minutes. This represents a significant reduction in time of 86 minutes or 78%. Watson excluded 94% of the patients automatically, providing criteria level evidence regarding the reason for exclusion, thus reducing the screening workload dramatically. Conclusions: IBM Watson CTM can help expedite the screening of patient charts for clinical trial eligibility and therefore may also help determine the feasibility of protocols to optimize site selection and enable higher and more efficient trial accruals.
Adherence to Guidelines for Breast Surveillance in Breast Cancer Survivors
Authors: Kathryn J. Ruddy, Lindsey Sangaralingham, Rachel A. Freedman, Sarah S. Mougalian, Heather Neuman, Caprice Greenberg, Ahmedin Jemal, Narjust Duma, Tufia C. Haddad, Valerie Lemaine, Karthik Ghosh, Tina J. Hieken, Katie Hunt, Celine Vachon, Cary P. Gross, Nilay D. Shah
Journal: Journal of the National Comprehensive Cancer Network (2018)

<section class="abstract"><p id="P1"><strong>Background:</strong> Guidelines recommend annual mammography after curative-intent treatment for breast cancer. The goal of this study was to assess contemporary patterns of breast imaging after breast cancer treatment. <strong>Methods:</strong> Administrative claims data were used to identify privately insured and Medicare Advantage beneficiaries with nonmetastatic breast cancer who had residual breast tissue (not bilateral mastectomy) after breast surgery between January 2005 and May 2015. We calculated the proportion of patients who had a mammogram, MRI, both, or neither during each of 5 subsequent 13-month periods. Multinomial logistic regression was used to assess associations between patient characteristics, healthcare use, and breast imaging in the first and fifth years after surgery. <strong>Results:</strong> A total of 27,212 patients were followed for a median of 2.9 years (interquartile range, 1.8–4.6) after definitive breast cancer surgery. In year 1, 78% were screened using mammography alone, 1% using MRI alone, and 8% using both tests; 13% did not undergo either. By year 5, the proportion of the remaining cohort (n=4,790) who had no breast imaging was 19%. Older age was associated with an increased likelihood of mammography and a decreased likelihood of MRI during the first and fifth years. Black race, mastectomy, chemotherapy, and no MRI at baseline were all associated with a decreased likelihood of both types of imaging. <strong>Conclusions:</strong> Even in an insured cohort, a substantial proportion of breast cancer survivors do not undergo annual surveillance breast imaging, particularly as time passes. Understanding factors associated with imaging in cancer survivors may help improve adherence to survivorship care guidelines. </section>
Medical school holds joint funeral for 74 children whose preserved bodies were found on site
Authors: Ned Stafford
Journal: BMJ (2018)

A German medical school has held a joint funeral service for 74 children, whose bodies had been inexplicably preserved in phenol solutions for more than half a century in the basement of the university.

The service was organised by the department of medicine at Martin Luther University of Halle-Wittenberg in Germany.

Heike Kielstein, director of the Institute of Anatomy and Cell Biology at the university, learned of the preserved bodies in 2011 on her first day on the job as director. The bodies were stored in two fixation containers and were not used for teaching or scientific …
‘Pre-activity movement control exercise programme to prevent injuries in youth rugby’: some concerns
Authors: Adam John White, John Batten, Graham Kirkwood, Eric Anderson, Allyson M Pollock
Journal: British Journal of Sports Medicine (2018)

All efforts to reduce injuries in school rugby are welcome and the cluster randomised controlled trial by Hislop and colleagues deserves attention.1 Here, the authors presented a preactivity exercise programme that trained strength, agility and balance, with reductions in time-loss injuries and concussions claimed. Yet we highlight fiveprimary concerns that arise from this study, which are particularly important given that the programme is now being implemented nationally.2 

Hislop and colleagues contacted 220 potentially eligible independent schools of which 40 consented to participate. There were 20 schools in each of the intervention and control groups—although 9 schools later withdrew (3 intervention, 6 control). Only seven schools (four intervention, three control) adhered to the programme at the optimal compliance rate of three or more weekly sessions. Yet no details are given of the characteristics and demographics of the …
Clonal Hematopoiesis: A New Layer in the Liquid Biopsy Story in Lung Cancer
Authors: Joshua Bauml, Benjamin Levy
Journal: Clinical Cancer Research (2018)

Cell-free DNA (cfDNA) is a unique biospecimen that contains multiple sources of DNA, including tumor, germline, fetal, and others. Clonal hematopoiesis, a process that leads to expansion of mutations in peripheral blood cells, is an additional source of DNA that adds a layer of complexity when interpreting results. Clin Cancer Res; 24(18); 4352-4. ©2018 AACRSee related article by Hu et al., p. 4437.
Phenomenon of Endothelial Antibody Capture: Principles and Potential for Locoregional Targeting of Hepatic Tumors
Authors: Nora Winkler, Felix Strübing, Wolfgang Groß, Walter Mier, Eduard Ryschich
Journal: Hepatology (2018)

The systemic drug circulation represents a source of adverse effects during tumor targeting. We studied the binding efficacy of endothelium‐specific antibodies after a very short contact with an antigen target, along with assessing the intravascular capture and targeting potential of these antibodies after locoregional injection. Fast‐binding anti–CD 146 (clone ME‐9F1) and anti‐CD31 (clone 390) antibodies were selected based on histological analysis of their binding activity. The efficacy of antibody capture by hepatic endothelium under different conditions was analyzed using an isolated liver perfusion model. The local enrichment of R‐phycoerythrin and 125 I‐conjugated antibody was studied in vivo in two hepatic tumor models using biodistribution, scintigraphic imaging, and fluorescence microscopy. Upon injection into the tumor‐feeding artery, the antibody was immediately captured in the microvasculature during the first passage. At doses not exceeding the saturation level of endothelial epitopes, the capture efficacy was almost 90%. We showed that the efficacy of endothelial capture is controlled by factors such as antibody affinity, number of binding sites on the endothelium, and microvascular flow rate. The targeting potential of endothelial capture was experimentally proven in vivo using scintigraphic imaging and biodistribution analysis after locoregional intra‐arterial injection of 125 I‐labeled antibodies in hepatic tumor models. Conclusion: The unique phenomenon of endothelial capture can broadly prevent systemic circulation of the antibody or antibody–drug conjugates applied by intravascular injection and may have specific relevance for targeting of hepatic tumors.
Local adaptation in European populations affected the genetics of psychiatric disorders and behavioral traits
Authors: Renato Polimanti, Manfred H. Kayser, Joel Gelernter
Journal: Genome Medicine (2018)

Recent studies have used genome-wide data to investigate evolutionary mechanisms related to behavioral phenotypes, identifying widespread signals of positive selection. Here, we conducted a genome-wide investigation to study whether the molecular mechanisms involved in these traits were affected by local adaptation. We performed a polygenic risk score analysis in a sample of 2455 individuals from 23 European populations with respect to variables related to geo-climate diversity, pathogen diversity, and language phonological complexity. The analysis was adjusted for the genetic diversity of European populations to ensure that the differences detected would reflect differences in environmental exposures. The top finding was related to the association between winter minimum temperature and schizophrenia. Additional significant geo-climate results were also observed with respect to bipolar disorder (sunny daylight), depressive symptoms (precipitation rate), major depressive disorder (precipitation rate), and subjective well-being (relative humidity). Beyond geo-climate variables, we also observed findings related to pathogen diversity and language phonological complexity: openness to experience was associated with protozoan diversity; conscientiousness and extraversion were associated with language consonants. We report that common variation associated with psychiatric disorders and behavioral traits was affected by processes related to local adaptation in European populations.
LSECtin and CD206 participate in the regulation of the hepatic inflammatory response to E coli in a model of cirrhosis
Authors: E. Caparrós, P. Piñero, O. Juanola, I. Gómez-Hurtado, P. Zapater, J.M. González-Navajas, Rubén Francés
Journal: Journal of Hepatology (2018)
A woman with intractable nausea and vomiting
Authors: Yan Zhang, Guanjun Kou, Yi Li, Yanqing Li
Journal: BMJ (2018)

A previously healthy 44 year old Chinese woman was referred by the emergency department to the gastroenterology ward with a seven week history of progressively worsening nausea and vomiting and weight loss of 13 kg. She did not have abdominal pain, distension, or diarrhoea. A general physician and a gastroenterologist had prescribed antidepressants (first flupentixol, then melitracen tablets, and finally olanzapine) for a functional gastrointestinal disorder, and she had been taking these for three weeks, as well as prokinetics (domperidone), and anti-emetics (domperidone and ondansetron), but she had not responded to treatment. Liver, kidney, thyroid function, and basic autoimmune antibodies were within normal ranges. Fasting blood glucose and glycated haemoglobin were normal. Previous gastroscopy and a computed tomography scan of the abdomen (conducted during the seven weeks of symptoms) showed no obvious abnormalities. Previous sagittal magnetic resonance imaging (MRI) of the head and cervical spine (taken three weeks after the first episode of nausea and vomiting) had shown a very small hyperintense lesion in the medulla oblongata, which had been considered normal (fig 1A). Fig 1 (A) Sagittal MRI of the head before admission. (B) Sagittal MRI of the head two months later. Arrows show a hyperintense lesion in the medulla oblongata Eight days after admission, the woman experienced metabolic alkalosis (caused by acute vomiting and hypokalaemia) and acute respiratory failure (caused by central hypoventilation and aspiration), and she was transferred to the intensive care unit for mechanical ventilation. Clinical examination found