tbuckley/cabot-search huggingface dataset:
Mixed Fibrinolytic Phenotypes in Decompensated Cirrhosis and Acute‐on‐Chronic Liver Failure with Hypofibrinolysis in Those With Complications and Poor Survival
Authors: Annabel Blasi, Vishal C. Patel, Jelle Adelmeijer, Sarah Azarian, Maria Hernandez Tejero, Andrea Calvo, Javier Fernández, William Bernal, Ton Lisman
Journal: Hepatology (2019)

Background and Aims Patients with liver disease acquire complex changes in their hemostatic system, which results in a fragile rebalanced status. The status of the fibrinolytic system is controversial, as is the role of fibrinolytic dysfunction in bleeding and thrombosis in patients with cirrhosis. Here, we aimed to determine fibrinolytic status and its relationship with outcome in acutely ill patients with cirrhosis. Approach and Results We assessed plasma fibrinolytic potential in a large cohort of patients with acutely decompensated cirrhosis (AD, n = 52) or acute‐on‐chronic liver failure (ACLF, n = 57). Compared with 40 healthy volunteers, median clot lysis times (CLTs) were shorter in patients with AD but comparable to controls in patients with ACLF. However, the variability in CLTs in patients was much larger than in healthy controls, and in both patient groups, a proportion of patients had clearly prolonged or shortened CLTs. The variability in CLTs in patients was not readily explained by variations in plasma levels of key fibrinolytic proteins. However, CLTs were clearly related to clinical characteristics, with longer CLTs in patients with sepsis and patients with any organ failure (as defined by the European Foundation for the Study of Chronic Liver Disease organ failure scores). CLTs were not different between patients that did or did not experience bleeding or a thrombotic event during follow‐up. Baseline CLTs were substantially longer in patients that died within 30 days of admission. Conclusions Our study demonstrates a mixed fibrinolytic phenotype in acutely ill patients with cirrhosis with baseline hypofibrinolysis associated with sepsis, organ failure, and short‐term mortality. These associations may be explained by defective clearance of intraorgan microthrombi that have been proposed to drive organ failure.
Bringing Clinical Staging to Youth Mental Health
Authors: Jai L. Shah
Journal: JAMA Psychiatry (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 Psychiatry 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 Psychiatry journal
Combination Treatment of the Oral CHK1 Inhibitor, SRA737, and Low-Dose Gemcitabine Enhances the Effect of Programmed Death Ligand 1 Blockade by Modulating the Immune Microenvironment in SCLC
Authors: Triparna Sen, Carminia M. Della Corte, Snezana Milutinovic, Robert J. Cardnell, Lixia Diao, Kavya Ramkumar, Carl M. Gay, C. Allison Stewart, Youhong Fan, Li Shen, Ryan J. Hansen, Bryan Strouse, Michael P. Hedrick, Christian A. Hassig, John V. Heymach, Jing Wang, Lauren A. Byers
Journal: Journal of Thoracic Oncology (2019)
A Review of Signal Processing Techniques for Non-Invasive Fetal Electrocardiography
Authors: Radana Kahankova, Radek Martinek, Rene Jaros, Khosrow Behbehani, Adam Matonia, Michal Jezewski, Joachim A. Behar
Journal: IEEE Reviews in Biomedical Engineering (2019)

Fetal electrocardiography (fECG) is a promising alternative to cardiotocography continuous fetal monitoring. Robust extraction of the fetal signal from the abdominal mixture of maternal and fetal electrocardiograms presents the greatest challenge to effective fECG monitoring. This is mainly due to the low amplitude of the fetal versus maternal electrocardiogram and to the non-stationarity of the recorded signals. In this review, we highlight key developments in advanced signal processing algorithms for non-invasive fECG extraction and the available open access resources (databases and source code). In particular, we highlight the advantages and limitations of these algorithms as well as key parameters that must be set to ensure their optimal performance. Improving or combining the current or developing new advanced signal processing methods may enable morphological analysis of the fetal electrocardiogram, which today is only possible using the invasive scalp electrocardiography method.
Developing a digital intervention for cancer survivors: an evidence-, theory- and person-based approach
Authors: Katherine Bradbury, Mary Steele, Teresa Corbett, Adam W. A. Geraghty, Adele Krusche, Elena Heber, Steph Easton, Tara Cheetham-Blake, Joanna Slodkowska-Barabasz, Andre Matthias Müller, Kirsten Smith, Laura J. Wilde, Liz Payne, Karmpaul Singh, Roger Bacon, Tamsin Burford, Kevin Summers, Lesley Turner, Alison Richardson, Eila Watson, Claire Foster, Paul Little, Lucy Yardley
Journal: npj Digital Medicine (2019)

Abstract This paper illustrates a rigorous approach to developing digital interventions using an evidence-, theory- and person-based approach. Intervention planning included a rapid scoping review that identified cancer survivors’ needs, including barriers and facilitators to intervention success. Review evidence ( N = 49 papers) informed the intervention’s Guiding Principles, theory-based behavioural analysis and logic model. The intervention was optimised based on feedback on a prototype intervention through interviews ( N = 96) with cancer survivors and focus groups with NHS staff and cancer charity workers ( N = 31). Interviews with cancer survivors highlighted barriers to engagement, such as concerns about physical activity worsening fatigue. Focus groups highlighted concerns about support appointment length and how to support distressed participants. Feedback informed intervention modifications, to maximise acceptability, feasibility and likelihood of behaviour change. Our systematic method for understanding user views enabled us to anticipate and address important barriers to engagement. This methodology may be useful to others developing digital interventions.
Abnormal Uptake and Air Trapping in Hypersensitivity Pneumonitis Detected on Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography
Authors: Yohji Matsusaka, Ichiro Kawada, Tadaki Nakahara, Yu Iwabuchi, Miho Kawaida, Masako Matsusaka, Masahiro Jinzaki
Journal: American Journal of Respiratory and Critical Care Medicine (2019)
The effect of cholesterol on cancer growth and metastasis: Experimental study with LDL receptor knockout mice.
Authors: Daniel Pu, Yuqi Cui, Zhenzhen Liu, Sampath Parthasarathy, Xuefeng Bai, Zhengou Liu
Journal: Journal of Clinical Oncology (2013)

e22071 Background: Cholesterol is an essential component for normal cell growth. However, epidemiological studies show cholesterol levels may be associated with cancer incidence. The Multiple Risk Factor Intervention Trial reported a significant inverse relationship between cholesterol levels and lung cancer. The effects of cholesterol on cancer growth and metastasis have not been established. The aim of the present study was to determine if cholesterol alters cancer growth or metastasis. Methods: The study used 48 wild-type mice and 18 LDL receptor knockout mice (LDLR-/-). Mice were randomized into 3 groups: Group I (wild-type mice fed normal chow, n=23); Group II (wild-type mice fed high lipid chow, n=25); Group III (LDLR-/- mice fed high lipid chow, n=18). Human melanoma cells were injected subcutaneously for the assessment of growth and intravenously for metastasis. Mice were followed for 4 weeks. At the end of the study, mice were weighed and autopsy was performed. Melanoma weight, metastasis, and blood cholesterol levels were evaluated. Data was analyzed using One-way ANOVA and Chi-square. Results: LDL-cholesterol level was significantly higher in Group III than Group I (1103±472 vs.28±6; p&lt;0.01). There was no significant difference in melanoma weight (2.74g ±1.77, 2.98g±1.98 vs. 2.18g±1.59, P=0.56) among the three subcutaneous injection groups. Lung metastasis was observed in all intravenous injection groups (11/11 vs. 10/10 vs. 8/8). There was no difference in melanoma weight or metastasis between male and female mice (P&gt;0.05). There was no difference in net weight gain among the subcutaneous injection groups (4.12g±2.50 vs. 2.64g±2.79 vs. 3.66g±1.96, P=0.30). However, among the intravenous injection groups, weight gain was observed in Group II (2.78g±2.67) and Group III (2.36g±1.73) and weight loss in Group I (-0.32g±1.34, P&lt;0.003). Conclusions: Cholesterol has no effect on melanoma growth or metastasis in mice. A high cholesterol diet may reduce weight loss in animals with metastatic melanoma. Further study is warranted to determine whether similar results exist in other types of cancers and to evaluate a possible beneficial effect of high lipid diets on patients with metastatic cancers.
PaFLO: Pazopanib with 5-fluorouracil, leucovorin, and oxaliplatin (FLO) as first-line treatment in advanced gastric cancer: A randomized phase II study of the Arbeitsgemeinschaft internistische Onkologie (AIO).
Authors: Kirstin Breithaupt, Dmitry Bichev, Mario Lorenz, Daniela Bohnen, Yasemin Dogan, Peter Schlattmann, Salah-Eddin Al-Batran, Markus Hermann Moehler, Peter C. Thuss-Patience
Journal: Journal of Clinical Oncology (2012)

TPS4138 Background: VEGF inhibition in gastric cancer shows promising improvement of remission rate and progression-free survival (Ohtsu et al., JCO 2011). Pazopanib is an orally available tyrosine kinase inhibitor (TKI) selectively inhibiting VEGFR-1, -2, -3, c-kit and PDGFR. It is approved for treating renal cell cancer. A phase-I trial showed good tolerability of pazopanib with full-dose FOLFOX in solid tumors (Brady et al., ASCO, 2009). FLO is a widely used combination for advanced gastric cancer recommended in national guidelines. Methods: 75 Patients with HER-2-negative locally advanced or metastatic adenocarcinoma of the stomach or the gastro-esophageal junction will be randomized in a 2:1 ratio to A: FLO (F 2600mg/m2 as 24h infusion, L 200mg/m2, O 85 mg/m2) d1 + pazopanib (800mg) d1-14 and B: FLO; repeated for 12 2-week cycles, followed by a maintenance therapy with pazopanib alone in A and an observation period in B until disease progression. Primary endpoint is progression-free survival rate (PFSR) at 6 months, secondary endpoints are PFSR at 9 and 12 months, median PFS, response rate, duration of response, toxicity, tolerability and overall survival. Additionally, we evaluate the predictive and prognostic relevance of PIGF, VEGF, and the respective soluble receptors sVEGFR1 and sVEGFR2 as biomarkers for clinicopathological parameters, clinical response to treatment and tumor volume change. Based on a phase-III trial demonstrating a 6-month PFSR of 44% with FLO (Al-Batran et al., 2008), we estimate a 6-month PFSR of 55% in the experimental group. Given an alpha error of 0.1 and a beta error of 0.2 in a Simon 2-stage minimax design, in the first stage ≥12 of 30 patients need to be progression free at 6 months to continue and after the second stage ≥25 of 50 patients should be progression free at 6 months to justify further evaluation. Randomization is performed to estimate selection bias according to pazopanib-specific exclusion criteria for comparison with historical data. Study protocol received ethics committee approval in November 2011 and is currently recruiting patients in 15 AIO centers.
Reap a Destiny: Divagations of a Taoist
Journal: Annals of Internal Medicine (1990)

Reviewsphysical state, arrangement and access to the records.Some of the historical sketches are tantalizingly incomplete, since so little is known ofthe firms.Descriptions vary from single items to quantities of material-often completely unsorted.Archives of many firms are scattered in several locations: those of British Xylorite Co. Ltd. (for example) are at Hackney Archives Dept., Suffolk Record Office, Vestry House, and the Science Museum.The handlist is completed by five invaluable indexes
Impact of patient age on quality of care in the treatment of colorectal cancer: Results from the Florida Initiative for Quality Cancer Care (FIQCC)
Authors: E. Siegel, D. Shibata, M. Malaga, W. Fulp, J. Lee, P. Jacobsen
Journal: Journal of Clinical Oncology (2009)

6548 Background: The quality of colorectal cancer (CRC) treatment has been suggested to vary by age, with older patients receiving poorer quality care. As part of a state-wide quality improvement effort, the FIQCC developed and implemented methods to assess the quality of care of several cancers among practices across the state of Florida. The current report focuses on the variability of adherence to CRC quality indicators for treatment and surveillance by patient age. Methods: Medical chart reviews were conducted of all patients first seen by a medical oncologist for CRC in 2006 at one of the 10 FIQCC sites (2 academic/8 community). Abstractors were trained and periodically monitored. Abstraction focused on assessing adherence to quality indicators consistent with evidence-, consensus-, and regulatory-based guidelines. Variability in adherence across age quartiles was evaluated using a Fisher's exact test. Of the 475 patients whose charts were reviewed, 53% were male, 80% were diagnosed with colon cancer and the median age was 65 years (range 27 to 92 years). Results: Adherence was consistently (p values&gt;.05) high across all age quartiles for presence of chemotherapy flow sheets (85%-93%), assessment of body-surface area (98%-100%) and performance of complete colon evaluation within 12 months of surgery (87%-89%). Moderate-to-low adherence was consistent by age for performance of CEA test before (74%-84%) or in the 6 months after (75%-82%) surgery/chemotherapy, and documentation of planned chemotherapy dose (51%-59%). Adherence decreased with increasing age for documentation of discussion/referral for chemotherapy in non-metastatic CRC cases (100%, 99%, 93%, and 89%; p = 0.001), but was consistently adhered to for all ages among metastatic cases (100%). The documentation of consent for patients treated with chemotherapy also varied by age-quartile (63%. 57%, 79%, and 73%; p = 0.02). Conclusions: Overall quality of CRC treatment was not consistent across the broad spectrum of patient age. Our data suggest age related disparity in the recommendation for adjuvant chemotherapy. Efforts should be made to understand the reasons for these differences and to improve and standardize the quality of CRC care for patients across all age groups. No significant financial relationships to disclose.
Targeting B7‐1 in immunotherapy
Authors: Rui Chen, Aravindhan Ganesan, Isobel Okoye, Elena Arutyunova, Shokrollah Elahi, M. Joanne Lemieux, Khaled Barakat
Journal: Medicinal Research Reviews (2019)

Abstract Modulation of T‐cell immune functions by blocking key immune checkpoint protein interactions using monoclonal antibodies (mAbs) has been an innovative immunotherapeutic strategy. T‐cells are regulated by different checkpoint proteins at the immunological synapse including the B7 ligands (B7‐1 or CD80 and B7‐2 or CD86), which is discussed in this review. These ligands are typically expressed on antigen presenting cells and interact with CD28 and cytotoxic T lymphocyte antigen‐4 (CTLA‐4) receptors on T‐cells. Their interactions with CD28 trigger a costimulatory signal that potentiates T‐cell activation, function and survival in response to cognate antigen. In addition, their interactions with CTLA‐4 can also inhibit certain effector T‐cell responses, particularly in response to sustained antigen stimulation. Through these mechanisms, the balance between T‐cell activation and suppression is maintained, preventing the occurrence of immunopathology. Given their crucial roles in immune regulation, targeting B7 ligands has been an attractive strategy in cancer and autoimmunity. This review presents an overview of the essential roles of B7‐1, highlighting the therapeutic benefits of modulating this protein in immunotherapy, and reviewing earlier and state‐of‐the‐art efforts in developing anti‐B7‐1 inhibitors. Finally, we discuss the challenges facing the design of selective B7‐1 inhibitors and present our perspectives for future developments.
How radiation oncologist accessibility influences treatment choice and quality in early-stage breast cancer: A SEER database analysis.
Authors: Thomas M. Churilla, Patrick E. Donnelly, Christopher A. Peters
Journal: Journal of Clinical Oncology (2012)

6031 Background: Mastectomy and breast conserving therapy (BCT, partial mastectomy and adjuvant radiotherapy) are equivalent in survival for treatment of early stage breast cancer. This study evaluated the impact of radiation oncologist accessibility on choice of mastectomy versus BCT, and the receipt of radiotherapy after BCT. Methods: In the NCI SEER database, breast cancer cases from 2004-2008 were selected with the following criteria: T2N1M0 or less, lobular or ductal histology, and treatment with simple mastectomy or partial mastectomy (+/-) adjuvant radiation. The HRSA Area Resource File was combined to define average radiation oncologist density (ROD, number of radiation oncologists/100K people) by county over the same time period. Tumor characteristics, demographic information, and ROD were evaluated with respect to mastectomy rates and receipt of radiation therapy after BCT in univariate and multivariate analyses. Results: In the 118,961 cases analyzed, mastectomy was performed 33.3% of the time relative to BCT. After adjustment for demographic and tumor variables, the odds of having mastectomy versus BCT were inversely associated with ROD (OR [95% CI] = 0.94 [0.93-0.96]; p&lt;0.001). Adjuvant radiation therapy was not administered in 23.4% of BCT cases. Likewise, the odds of having BCT without adjuvant radiation were inversely associated with ROD (0.96 [0.95-0.98]; p&lt;0.001, table). Conclusions: There was a significant, inverse and linear relationship between ROD and mastectomy rates independent of demographic and tumor variables. An inverse trend was also observed for the omission of radiotherapy after BCT. Access to radiation oncologists was a factor in surgical choice and receiving appropriate BCT in early stage breast cancer. [Table: see text]
Antiproliferative, antiangiogenesis, and reversal of chemoresistance by specific cathepsin L inhibitors
Authors: A. Rebbaa, E. Dyskin, E. Dier, C. Gallati, C. Honko, T. Simone, M. Yalcin, T. Sudha, S. A. Mousa
Journal: Journal of Clinical Oncology (2009)

e14643 Background: Uncontrolled proliferation, enhanced angiogenesis and the development of resistance to therapy are hallmarks of cancer; therefore, the development of approaches to simultaneously target these three processes would be the most desirable. Previous work from our laboratory has demonstrated that NapSul-Ile-Trp-CHO (NSITC), a specific inhibitors of cathepsin L, and its analogs strongly inhibited cancer cell proliferation and suppressed the development of drug resistance in vitro (Zheng X. et al., 2004 Cancer Res. 64:1773–80). In the present study, we sought to investigate the validity of these observations in vivo, and to dissect the underlying mechanism(s). Methods: Nude mice (Strain CD1) bearing xenografts of doxorubicin resistant neuroblastoma cell line SKN-SH/R were challenged with doxorubicin (1.5 mg/Kg) alone, NSITC (20 mg/kg) alone or the combination of both. The effect of NSITC on tumor angiogenesis was also investigated using the Chick Chorioallantoic Membrane (CAM). Putative mechanisms by which NSITC inhibits cellular proliferation, drug resistance and angiogenesis were studied using cancer and endothelial cells maintained in culture. Results: The in vivo data indicated that doxorubicin alone had no effect on tumor growth, however NSITC alone exerted 40% inhibition and the combination of both drugs reduced tumor growth by about 90%. NSITC also caused a 125% inhibition of blood vessel branching in the CAM model (at 1 μg/CAM). Investigation of the underlying mechanisms of its action revealed that at low concentration, NSITC forces cancer cells into senescence, preventing them from developing resistance to classical anticancer agents, and at high concentrations, it induced autophagic cell death. NSITC also strongly inhibited the proliferation and invasion of endothelial cells in a dose dependent manner with more than 90% inhibition at 20 μM. Conclusions: Overall, these findings suggest that NSITC has multi-anticancer functions and thus, may represent a potential drug candidate for the treatment of aggressive malignancies. No significant financial relationships to disclose.
Neoadjuvant Chemotherapy With Cisplatin and Gemcitabine Followed by Chemoradiation Versus Chemoradiation for Locally Advanced Cervical Cancer: A Randomized Phase II Trial
Authors: Samantha Cabral S. da Costa, Renata Colombo Bonadio, Flavia Carolina G. Gabrielli, Andrea S. Aranha, Maria Luiza N. Dias Genta, Vanessa C. Miranda, Daniela de Freitas, Elias Abdo Filho, Patrícia A.O. Ferreira, Karime K. Machado, Mariana Scaranti, Heloísa de A. Carvalho, Maria Del Pilar Estevez-Diz
Journal: Journal of Clinical Oncology (2019)

Although chemoradiation therapy (CRT) with cisplatin remains the standard treatment of patients with locally advanced cervical cancer (LACC), 40% of patients present with disease recurrence. Additional treatment strategies are required to improve outcomes. We conducted a trial to evaluate the efficacy and safety of neoadjuvant chemotherapy (NAC) with cisplatin and gemcitabine followed by CRT.In this phase II trial, patients with LACC (International Federation of Gynecology and Obstetrics stage IIB to IVA or with positive lymph nodes) were randomly assigned to three cycles of NAC with cisplatin and gemcitabine followed by standard CRT with weekly cisplatin plus pelvic radiotherapy or to standard CRT alone. The primary end point was 3-year progression-free survival (PFS). Secondary end points were response rate, 3-year locoregional control, 3-year overall survival (OS), safety, and quality of life.From 107 patients enrolled in the trial, 55 were randomly assigned to the NAC arm and 52 to the CRT-alone arm. The majority of patients had squamous cell carcinoma (87.8%). After a median follow-up of 31.7 months, NAC was associated with an inferior PFS, with 3-year PFS rates of 40.9% v 60.4% in the CRT arm (hazard ratio, 1.84; 95% CI, 1.04 to 3.26; P = .033). NAC also was associated with a lower OS (3-year OS rate, 60.7% v 86.8%; hazard ratio, 2.79; 95% CI, 1.29 to 6.01; P = .006). After treatment completion, complete response rates were 56.3% in the NAC arm and 80.3% in the CRT arm (P = .008). Toxicities were similar in both arms, with the exception of hypomagnesemia and neuropathy being more common with NAC.This study shows that the addition of NAC consisting of cisplatin and gemcitabine to standard CRT is not superior and is possibly inferior to CRT alone for the treatment of LACC.