tbuckley/cabot-search huggingface dataset:
Hepatic spheroids used as an in vitro model to study malaria relapse
Authors: Adeline C.Y. Chua, Abhishek Ananthanarayanan, Jessica Jie Ying Ong, Jen Yi Wong, Andy Yip, Nisha Hari Singh, Yinghua Qu, Laurent Dembele, Michael McMillian, Ratawan Ubalee, Silas Davidson, Anchalee Tungtaeng, Rawiwan Imerbsin, Kapish Gupta, Chiara Andolina, Fan Lee, Kevin S-W Tan, François Nosten, Bruce Russell, Amber Lange, Thierry T. Diagana, Laurent Rénia, Bryan K.S. Yeung, Hanry Yu, Pablo Bifani
Journal: Biomaterials (2019)

Hypnozoites are the liver stage non-dividing form of the malaria parasite that are responsible for relapse and acts as a natural reservoir for human malaria Plasmodium vivax and P. ovale as well as a phylogenetically related simian malaria P. cynomolgi. Our understanding of hypnozoite biology remains limited due to the technical challenge of requiring the use of primary hepatocytes and the lack of robust and predictive in vitro models. In this study, we developed a malaria liver stage model using 3D spheroid-cultured primary hepatocytes. The infection of primary hepatocytes in suspension led to increased infectivity of both P. cynomolgi and P. vivax infections. We demonstrated that this hepatic spheroid model was capable of maintaining long term viability, hepatocyte specific functions and cell polarity which enhanced permissiveness and thus, permitting for the complete development of both P. cynomolgi and P. vivax liver stage parasites in the infected spheroids. The model described here was able to capture the full liver stage cycle starting with sporozoites and ending in the release of hepatic merozoites capable of invading simian erythrocytes in vitro. Finally, we showed that this system can be used for compound screening to discriminate between causal prophylactic and cidal antimalarials activity in vitro for relapsing malaria.
CHARACTERISTICS OF ACUTE SEVERE LOWER GASTROINTESTINAL BLEEDING IN PATIENTS WITH CROHN'S DISEASE
Authors: BI Jang, MC Kim, MK Kang, JH Cho, SB Kim, KH Kim, KO Kim, SH Lee, TN Kim
Journal: Endoscopy (2019)

Acute severe lower gastrointestinal bleeding (LGIB) is a rare complication in Crohn's disease, which is a therapeutic challenge due to variety of clinical manifestations and extents of disease. We aimed to compare the characteristics of the first bleeding and re-bleeding episodes in patients with Crohn's disease.
Hyperthermia Nanofiber Platform Synergized by Sustained Release of Paclitaxel to Improve Antitumor Efficiency
Authors: Eri Niiyama, Koichiro Uto, Chun Man Lee, Kazuma Sakura, Mitsuhiro Ebara
Journal: Advanced Healthcare Materials (2019)

Abstract Effective cancer therapy can be achieved by designing a smart nanofiber system with the combination of chemotherapy and hyperthermia. This study demonstrates the in vivo antitumor effect of a nanofiber mesh that can deliver heat and antitumor drug in a controlled manner. The mesh is composed of biodegradable poly(ε‐caprolactone) (PCL) with paclitaxel (PTX) and magnetic nanoparticles (MNPs). The PCL mesh releases PTX slowly for at least 6 weeks when tested in vitro. The prolonged therapeutic effect is observed in vivo as a continuous release of medication from the mesh over an extended period of time compared with direct injection of PTX into the tumor site. In addition, the synergistic anticancer effect is achieved upon excitation of the mesh with an alternating magnetic field because the MNPs within the nanofiber generate localized heat which causes heat‐induced cell killing as well as enhanced chemotherapeutic effect of PTX. Based on these results, the smart nanofiber system may be very promising for cancer therapeutics in the future and may provide knowledge for new development of localized drug delivery.
SAFETY PROFILE OF THE POSE PROCEDURE
Authors: AJ del Pozo-Garcia, DR de la Cruz, J Rosado, E Ulloa Márquez, F Sánchez Gómez
Journal: Endoscopy (2019)

Bariatric surgery, diet and lifestyle modifications, and non-exogenous drugs, have not managed to stop obesity worldwide expansion. Several bariatric endoscopic techniques emerge as safe and cost-effective promising alternatives. Our aim was to evaluate the security of the POSE (Primary Obesity Surgery Endolumenal) procedure.
The Metabolic Basis of Kidney Cancer
Authors: W. Marston Linehan, Laura S. Schmidt, Daniel R. Crooks, Darmood Wei, Ramaprasad Srinivasan, Martin Lang, Christopher J. Ricketts
Journal: Cancer Discovery (2019)

Abstract Kidney cancer is not a single disease but represents several distinct types of cancer that have defining histologies and genetic alterations and that follow different clinical courses and have different responses to therapy. Mutation of genes associated with kidney cancer, such as VHL, FLCN, TFE3, FH, or SDHB, dysregulates the tumor's responses to changes in oxygen, iron, nutrient, or energy levels. The identification of these varying genetic bases of kidney cancer has increased our understanding of the biology of this cancer, allowing the development of targeted therapies and the appreciation that it is a cancer driven by metabolic alterations. Significance: Kidney cancer is a complex disease composed of different types of cancer that present with different histologies, clinical courses, genetic changes, and responses to therapy. This review describes the known genetic changes within kidney cancer, how they alter tumor metabolism, and how these metabolic changes can be therapeutically targeted.
Abstract 1848: PPARγ function is attenuated by full length androgen receptor and the AR-V7 variant in human prostate cancer cells
Authors: Emuejevoke Olokpa, Lamonica V. Stewart
Journal: Cancer Research (2015)

Abstract The peroxisome proliferator activated receptor gamma (PPARγ) is a ligand-activated transcription factor that regulates in vitro and in vivo growth of castration-resistant human prostate cancer (PCa) cells. However, the factors that control expression of PPARγ within human PCa have not been characterized. We have previously shown that the androgen dihydrotestosterone decreases PPARγ levels and transcriptional activity in human PCa cells. Dihydrotestosterone serves as a high affinity ligand for the 110 kD form of the androgen receptor (AR-FL). Recent studies have shown the development of castration-resistant forms of prostate cancer is not only due to reactivation of AR-FL but also results from the expression of androgen receptor splice variants (ARVs) that lack the ligand-binding domain of the receptor. The goal of this study is to define the extent to which AR-FL and an ARV found in castration-resistant prostate cancer, AR-V7, regulate PPARγ expression and function. We first examined the role of AR-FL in the AR-positive C4-2 cell line. siRNA-mediated knockdown of endogenous AR-FL within C4-2 cells increased PPARγ protein and transcriptional activity. We next used reporter assays to further define the role of AR-FL and AR-V7 in PPARγ function. In these experiments, we first transfected plasmid vectors that express the AR-V7 or AR-FL into the AR null PC-3 prostate cancer cell line. A luciferase-based reporter assay was then used to measure alterations in PPARγ transcriptional activity within transfected cells. The addition of AR-FL to PC-3 cells resulted in reduced basal PPARγ luciferase activity. The ability of the ligand rosiglitazone to increase PPARγ activation was also suppressed in AR-FL positive PC-3 cells. A comparable decrease in ligand-induced PPARγ activation was detected in PC-3 cells that expressed AR-V7. The reduction in PPARγ activity produced by AR-FL and AR-V7 was likely not due to alterations in PPAR gamma expression, for we did not detect a consistent reduction in PPARγ mRNA and protein in transfected cells. Overall these data suggest that both AR-FL and AR-V7 are negative regulators of PPARγ function. Moreover, the AR-V7 stimulated reduction in PPARγ activity does not require the presence of AR-FL. Studies currently are underway to define the effect of endogenous AR-V7 on PPARγ expression and activity. This project was supported by NIGMS RISE grant (2R25GM059994-13), a NCI Mentored Career Development Award (K01CA114253), and the Vanderbilt CTSA grant UL1 RR024975-01 from NCRR/NIH. Citation Format: Emuejevoke Olokpa, Lamonica V. Stewart. PPARγ function is attenuated by full length androgen receptor and the AR-V7 variant in human prostate cancer cells. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1848. doi:10.1158/1538-7445.AM2015-1848
RT-PCR studies in patients with chronic myeloid leukemia (CML) in remission 5 years after allogeneic stem cell transplant (SCT) define risk of subsequent relapse
Authors: T. I. Mughal, A. Yong, R. M. Szydlo, J. Kaeda, N. C.P. Cross, C. Craddock, E. Kanfer, J. F. Apperley, J. M. Goldman
Journal: Blood (2000)
The Need for Federal Regulation of Marijuana Marketing
Authors: John W. Ayers, Theodore L. Caputi, Eric C. Leas
Journal: JAMA (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 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
STANDARDIZED PROACTIVE ENDOSCOPIC AND SURGICAL INTERVENTIONS FOR MANAGEMENT OF PATIENTS WITH BOERHAAVE SYNDROM TO REDUCE MORTALITY: A RETROSPECTIVE ANALYSIS
Authors: D Wichmann, L Herrmann, B Mothes, U Schweizer, A Königsrainer, U Schempf, M Goetz, V Steger, G Loske, D Stueker
Journal: Endoscopy (2019)

Boerhaave Syndrome (BS) is a post emetic transmural rupture of the oesophagus. It is a devastating event associated with a high morbidity and mortality rate. Enteric leakage into the thoracic or abdominal cavity causes mediastinitis, sepsis and multisystem organ failure. New strategy combining minimal invasive tools and interdisciplinary therapy was introduced to treat patients with a rupture of the oesophagus following a standard operating procedure.
LONG-TERM SURVIVAL ANALYSIS AFTER ENDOSCOPIC STENTING AS A BRIDGE TO SURGERY FOR MALIGNANT COLONIC OBSTRUCTION: COMPARISON WITH EMERGENCY SURGERY
Authors: R Corsato Scomparin, B Costa Martins, CF Sparapan Marques, C Nahas, F Shiguehissa Kawaguti, L Lenz, A Safatle-Ribeiro, G Andrade de Paulo, U Ribeiro, S Nahas, F Maluf-Filho
Journal: Endoscopy (2019)

Colorectal self-expanding metal stents (SEMS) can be used as a bridge therapy in acute malignant colorectal obstruction for elective surgical treatment in better clinical conditions. There are reports of higher rates of tumor recurrence in the long-term and worse survival in the SEMS group. The aim of this study was to compare the long-term results of colorectal SEMS versus emergency surgery in patients with malignant colorectal obstruction with curative purposes. The main outcome was overall survival rate.
Solid Fuel Use and Incident COPD in Chinese Adults: Findings from the China Kadoorie Biobank
Authors: Jiachen Li, Chenxi Qin, Jun Lv, Yu Guo, Zheng Bian, Weiwei Zhou, Jianming Hu, Yidan Zhang, Junshi Chen, Weihua Cao, Canqing Yu, Liming Li
Journal: Environmental Health Perspectives (2019)

Background: Solid fuels are widely used in China. Household air pollution from the burning of solid fuels may increase the risk of chronic obstructive pulmonary disease (COPD), but prospective evidence is limited. Objectives: We examined the association of solid fuel use for cooking and heating with the risk of COPD in a prospective cohort study. Methods: Participants were from the China Kadoorie Biobank. Current and previous fuels used for household cooking and heating were self-reported at baseline in 2004–2008. In the present study, “solid fuels” refers to coal and wood, whereas “cleaner fuels” refers to energy sources that presumably produce lower levels of indoor pollution, including electricity, gas, and central heating. A total of 475,827 adults 30–79 y of age without prevalent COPD were followed through the end of 2015. We used adjusted Cox regression models to estimate hazard ratios for COPD. Results: Over 9.1 y of follow-up, 9,835 incident COPD cases were reported. Compared with the use of cleaner fuels for cooking, using coal and wood for cooking was positively associated with COPD, with fully adjusted HRs of 1.06 (95% CI: 0.98, 1.15) and 1.14 (95% CI: 1.06, 1.23), respectively. Adjusted HRs for heating with coal and wood were 1.16 (95% CI: 1.04, 1.29) and 1.21 (95% CI: 1.09, 1.35), respectively. The positive association between cooking with solid fuel and COPD appeared to be limited to women and never- (vs. ever-) smokers. COPD risk increased with a higher number of years of solid fuel use for heating and wood use for cooking. Conclusions: The use of solid fuel for cooking and heating was associated with the increased risk of COPD in this prospective cohort study. Studies with more accurate exposure assessment are needed to confirm the association. https://doi.org/10.1289/EHP2856
Drainage biliaire endoscopique dans les cancers bilio-pancréatiques: résultats et facteurs associés à propos de 105 cas
Authors: S Morabit, H Seddik, F Bouhamou, S Mrabti, I El Koti, S Sentissi, A Benkirane
Journal: Endoscopy (2019)

Le drainage biliaire endoscopique demeure le traitement palliatif de référence dans les sténoses néoplasiques biliaires, chez les patients présentant une contre indication à l'exérèse, notamment du fait de métastases ou d'un stade localement avancé. L'objectif de notre étude est de préciser rétrospectivement les résultats de cette technique dans notre formation, ainsi que les différents facteurs associés à son échec ou son succès.
Abstract 3625: Thyroid hormone, thyroxine, promotes cell proliferation and β-catenin activation in colorectal cancer
Authors: Yee-Shin Lee, Meng-Ti Hsieh, Yu-Tang Chin, Aleck Hercbergs, Paul J. Davis, Han-Chung Wu, Hung-Yun Lin
Journal: Cancer Research (2017)

Abstract Backgrounds: Being a crucial hormone regulating growth, metabolism and various physiological processes, the status of thyroid hormone has long been implicated in cancer risks and tumor developments. In the present study, we aimed to look at the role of thyroid hormone, thyroxine (T4), in colorectal cancer cell proliferation and β-catenin activation, which is highly involved in both normal and oncogenic developments of the gut. Materials and Methods: The effects of T4 in colorectal cancer cell lines HCT 116 (APC wild type) and HT-29 (APC mutant) as well as the primary cells derived from colorectal cancer patients were studied. Cell proliferation was evaluated according to cell counting, MTT assay and qRT-PCR. The activation of β-catenin was examined using Western blotting, qRT-PCR and immunoprecipitation. Results: The results showed that T4 increased the cell number of both HCT 116 and HT-29 cells compared to the untreated cells. In both cell lines, T4 induced nuclear β-catenin accumulation and the protein levels of WNT/β-catenin targets Cyclin D1 and c-Myc. The mRNA expression of CTNNB1 was elevated by T4 in HCT 116 cells, but not in HT-29 cells. In APC wild type HCT 116 cells, T4 increased the WNT4 mRNA expression and decreased the association between β-catenin and the WNT-regulated β-catenin destruction complex. Moreover, the cell numbers of T4-treated primary cells were higher compared to the untreated cells while the mRNA expressions of proliferative genes PCNA, CCND1 and c-Myc were elevated by T4. In the primary cells, T4-induced nuclear β-catenin accumulation, protein levels of Cyclin D1 and c-Myc, and mRNA expressions of CTNNB1 and WNT4 were also observed. Conclusions: T4 promoted cell proliferation and β-catenin activation in colorectal cancer. In the cells with different APC mutation status, the activation of β-catenin was regulated by different mechanisms. Citation Format: Yee-Shin Lee, Meng-Ti Hsieh, Yu-Tang Chin, Aleck Hercbergs, Paul J. Davis, Han-Chung Wu, Hung-Yun Lin. Thyroid hormone, thyroxine, promotes cell proliferation and β-catenin activation in colorectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3625. doi:10.1158/1538-7445.AM2017-3625
Long-Term Effectiveness of Cognitive Behavioral Therapy in Routine Outpatient Care: A 5- to 20-Year Follow-Up Study
Authors: Ruth von Brachel, Gerrit Hirschfeld, Arleta Berner, Ulrike Willutzki, Tobias Teismann, Jan Christopher Cwik, Julia Velten, Dietmar Schulte, Jürgen Margraf
Journal: Psychotherapy and Psychosomatics (2019)

Long-term follow-ups several years after receiving cognitive behavioral therapy (CBT) are scarce and most of the existing literature describes follow-up data of randomized-controlled trials. Thus, very little is known about the long-term effects of CBT in routine care.We investigated psychological functioning in a sample of 263 former outpatients who had received CBT for a variety of mental disorders such as depression, anxiety-, eating- or somatoform disorders 8.06 (SD 5.08) years after treatment termination. All participants completed a diagnostic interview as well as the Brief-Symptom Inventory (BSI) and the Beck Depression Inventory (BDI). Effect sizes and response rates according to Jacobson and Truax [J Consult Clin Psychol 1991;59:12-9] were calculated from pre- to posttreatment and from pretreatment to follow-up assessment.Pre- to posttreatment effect sizes ranged between 0.75 (BDI) and 0.63 (BSI) and pretreatment to follow-up effect sizes were 0.92 (BDI) and 0.75 (BSI). Of all patients, 29% (BDI) and 17% (BSI) experienced clinically significant change at posttreatment and 42% (BDI) and 24% (BSI) at follow-up.The results point to the long-term effectiveness of CBT under routine conditions for a wide array of problems, especially when compared to the long-term effects of medical treatment. It is noteworthy that the results at follow-up were even better than at posttreatment, indicating further improvement. However, about a quarter of the patients did not respond sufficiently to therapy, neither concerning short-term nor long-term effects.
Intratumoral Activity of the CXCR3 Chemokine System Is Required for the Efficacy of Anti-PD-1 Therapy
Authors: Melvyn T. Chow, Aleksandra J. Ozga, Rachel L. Servis, Dennie T. Frederick, Jennifer A. Lo, David E. Fisher, Gordon J. Freeman, Genevieve M. Boland, Andrew D. Luster
Journal: Immunity (2019)
SCAN-B-rec: Infrastructure, technology and clinical research platform to profile and monitor metastatic breast cancer
Authors: A. Bosch, A.-M. Larsson, K. Holm, Å. Borg, J. Staaf, L. Saal
Journal: Annals of Oncology (2019)

Background: Great advances have been made in the molecular characterisation of advanced breast cancer (ABC). Still, clinical practice has not changed in terms of assessment of response to therapy. Radiologic imaging and clinical examination help determine disease burden and treatment efficacy. However, imaging heavily relies on the expertise of the radiologist and oncologist and has high intra- and inter-reader variability. Circulating tumor cells (CTCs) enumeration with CellSearchâ has confirmed independent prognostic value compared to conventional radiology and serum markers such as CA15-3. Similarly, quantification of circulating tumor DNA (ctDNA) has also prognostic value in ABC. ctDNA analysis further provides critical information on the mutational status of specific genes which can predict sensitivity to specific targeted therapeutics. Trial design: The SCAN-B-rec (NCT03758976) is a prospective multi-center observational study that aims to explore the value provided by ctDNA analysis to determine treatment efficacy when compared to CTCs and conventional radiological imaging in a "real-world" setting. A total of 350 patients with pathologically-confirmed ABC will be recruited. Plasma ctDNA will be extracted and analysed before treatment start (T0) and after three months of therapy (T1). The relative change in mutant allele frequency (MAF) between these two time-points will be calculated. Response to treatment will be defined using pre-specified cut-offs. A comparison with response to treatment according to conventional radiological imaging (RECIST criteria) and CTC enumeration at the same time points will be performed. The primary objective is to establish the prognostic value of ctDNA to predict overall survival. The study will also explore the added value provided by ctDNA mutational analysis to determine biomarkers of sensitivity and resistance to targeted therapeutics approved to treat ABC or other solid tumors that could be used "off-label". We expect that ctDNA quantification will give a more accurate read-out of treatment response, providing better prognostic information in ABC as well as information on drug sensitivity/resistance in a large proportion of ABC patients. Clinical trial identification: SCAN-B-rec (NCT03758976). Legal entity responsible for the study: Lund University Hospital (Region Skane). Funding: BioCARE, Cancer Fonden, ALF (Region Skåne) and Svenska Läkaresällskapet. Disclosure: A. Bosch: Advisory board meetings: Pfizer, Novartis in Sweden. These have been non-remunarated. L. Saal: CEO: AGA Diagnostics. All other authors have declared no conflicts of interest.
Regulation of interferon signaling in response to gut microbes by autophagy
Authors: Patricia K. Martin, Ken Cadwell
Journal: Gut Microbes (2019)

The cellular degradative pathway of autophagy prevents unrestrained inflammatory signaling by removing intracellular microbes, damaged organelles, and other factors that trigger immune reactions. Consistent with this function, a common variant of the autophagy gene ATG16L1 is associated with susceptibility to inflammatory bowel disease (IBD), a disorder characterized by a chronic immune reaction directed against the gut microbiota. We recently contributed to our understanding of the link between autophagy and inflammatory signaling in the intestine by demonstrating that autophagy proteins including ATG16L1 are necessary in the epithelium to prevent a spontaneous type I interferon response to the gut microbiota. Enhanced innate immunity that occurs upon autophagy inhibition is protective in mouse models of infection by an enteric bacterial pathogen and acute epithelial injury. Although avoiding excess immune reactions towards the microbiota is necessary to prevent IBD, these observations indicate that autophagy hampers productive immunity at the intestinal epithelial barrier in certain contexts. Here, we discuss how this counterintuitive consequence of autophagy inhibition can be reconciled with the established beneficial role of the pathway.