tbuckley/cabot-search huggingface dataset:
Abstract 10871: Changes in Lipid Profile of Obese Patients Following Contemporary Bariatric Surgery: A Meta-Analysis
Authors: Sean P Heffron, Amar Parikh, Alexandar Volodarskiy, Christine Ren-Fielding, Arthur Schwartzbard, Joseph Nicholson, Sripal Bangalore
Journal: Circulation (2015)

Background: Dyslipidemia drives the development of atherosclerosis and obese individuals frequently manifest dyslipidemia. Although metabolic surgery was originally performed to treat hypercholesterolemia, the effect of contemporary bariatric surgery on serum lipids has not been systematically characterized. Methods: We queried MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials from inception through the second week of May, 2015 for studies with at least 20 obese adults who underwent Roux-en-Y Gastric Bypass (RYGBP), Adjustable Gastric Banding, Bilio-Pancreatic Diversion (BPD), or Sleeve Gastrectomy reporting lipid data at baseline and at least one year following surgery. Primary outcome measures were change in total cholesterol (TC), LDL-cholesterol (LDL-C), HDL-cholesterol (HDL-C), and triglyceride values from baseline to 1-year follow-up after bariatric surgery. Results: There were 180 articles eligible for inclusion with 25,189 obese subjects (mean body mass index 45.1±4.8 kg/m2) and over 47,800 patient-years follow-up. In patients who underwent surgery, compared to baseline, there were significant reductions in TC, LDL-C, triglycerides and a significant increase in HDL-C (P&lt;0.00001 for all), although the magnitude of change varied with surgical type (Pinteraction &lt;0.05; Figure). The magnitude of the change in lipid parameters with surgery (overall) was significantly greater than the change in lipid parameters among patients who did not undergo surgery (Figure). Results were similar beyond one year. Conclusions: Contemporary bariatric surgical techniques produce significant improvements in lipid parameters at one year following surgery, which are greater in magnitude than those in patients not undergoing surgery. However, the magnitude of change in lipid parameters varies widely with surgical type, indicating that these differences may be relevant in deciding the most appropriate technique for a given patient.
Evaluation of five automated and one manual method for Toxoplasma and human DNA extraction from artificially spiked amniotic fluid
Authors: H. Yera, L. Ménégaut, M.-P. Brenier-Pinchart, F. Touafek, P. Bastien, F. Dalle, Sophie Cassaing, Laurence Delhaes, Denis Filisetti, Jean Ménotti, Hervé Pelloux, Florence Robert-Gangneux, Yvon Sterkers, Emmanuelle Varlet-Marie
Journal: Clinical Microbiology and Infection (2018)
Epigenetic regulation in B-cell maturation and its dysregulation in autoimmunity
Authors: Haijing Wu, Yaxiong Deng, Yu Feng, Di Long, Kongyang Ma, Xiaohui Wang, Ming Zhao, Liwei Lu, Qianjin Lu
Journal: Cellular and Molecular Immunology (2018)

B cells have a critical role in the initiation and acceleration of autoimmune diseases, especially those mediated by autoantibodies. In the peripheral lymphoid system, mature B cells are activated by self or/and foreign antigens and signals from helper T cells for differentiating into either memory B cells or antibody-producing plasma cells. Accumulating evidence has shown that epigenetic regulations modulate somatic hypermutation and class switch DNA recombination during B-cell activation and differentiation. Any abnormalities in these complex regulatory processes may contribute to aberrant antibody production, resulting in autoimmune pathogenesis such as systemic lupus erythematosus. Newly generated knowledge from advanced modern technologies such as next-generation sequencing, single-cell sequencing and DNA methylation sequencing has enabled us to better understand B-cell biology and its role in autoimmune development. Thus this review aims to summarize current research progress in epigenetic modifications contributing to B-cell activation and differentiation, especially under autoimmune conditions such as lupus, rheumatoid arthritis and type 1 diabetes.
Neonatal Jaundice and Risk of Allergic Diseases By 6 Years of Age: A Cohort Study
Authors: Chun-Chun Gau, Wan Fang Lee, I-Chun Lu, Li-Lun Lin, Chao-Yi Wu, Hui-Ju Tsai, Tsung-Chieh Yao
Journal: Journal of Allergy and Clinical Immunology (2018)
Role of Brca1 in regulating the ovarian cycle
Authors: Hao Hong, Hai-Yun Yen, Robert Maxson, Louis Dubeau
Journal: Cancer Research (2007)

3866   Most women with familial breast and ovarian cancer carry germline mutations in BRCA1. Epidemiological studies strongly suggest that menstrual cycle activity is associated with increased risk of sporadic ovarian carcinoma. We hypothesized that BRCA1 mutations might predispose to gynecological cancers indirectly by influencing the menstrual cycle. To test our hypothesis, we utilized the Cre-LoxP approach to inactivate Brca1 specifically in ovarian granulosa cells, which play a critical role regulating menstrual cycle by secreting a number of reproductive hormones. We previously reported that 60% of mutant mice developed benign serous ovarian and/or uterine cystadenomas. These cystic tumors did not develop in granulosa cells and resembled human serous cystadnomas, which are benign tumors composed of the same cell type as ovarian serous carcinomas.  The estrus cycle is composed of four stages: pre-estrus, estrus, metestrus and diestrus. We sought to determine whether Brca1 inactivation in granulosa cells influences this cycle in our mouse model by measuring and comparing the length of each phase in a group of age-matched mutant  versus  normal mice when they were 3 months, 8 months and 14 months old. The mice were sacrificed at 14 months in order to correlate any cyclic change to tumor predisposition. Daily vaginal lavages were obtained over a period spanning several consecutive cycles. The samples were spread on glass slides and stained with Papanicolou (PAP) stain. The average length of each phase was calculated for each individual mouse and used to calculate the average length ± SD for the entire group.  An increase in the length of proestrus was seen in mutant mice that was most significant at 8 months (1.6 ± 0.45 days  versus  0.9 ± 0.23 days, P=0.003). Proestrus corresponds to the follicular phase of the human menstrual cycle. There was also a decrease in the length of metestrus (corresponding to the luteal phase in the human menstrual cycle) resulting in a shorter time period between consecutive estrus phases in the mutant mice. In the 8 month old age group, mutant mice that developed cystadenomas underwent a total of 6.4 ± 0.83  estrus over a 30 days period compared to 4.0 ± 0.01 in mutant mice that did not develop tumors (p = 0.03), suggesting a correlation between cycle abnormalities and tumor predisposition. Furthermore, 75% of mice that showed cycle abnormalities developed cysts compared to 33% of those who had normal cycles.  Given that proestrus is characterized by estrogen secretion while estrogen and progesterone are both secreted during metestrus, the results suggest that mutant mice have a relative increase in estrogen stimulation unopposed by progesterone. This raises the possibility that similar hormonal changes, if present in women with germline BRCA1 mutations, might account for predisposition to breast and reproductive cancers in these individuals.
Response to: ‘Patterns of PD-L1 expression and CD8 T cell infiltration in gastric adenocarcinomas and associated immune stroma’
Authors: Sascha Rahn, Sandra Krüger, Christoph Röcken, Ole Helm, Susanne Sebens
Journal: Gut (2018)

We read with interest the manuscript by Thompson et al recently published in Gut 1 highlighting the expression of programmed death ligand 1 (PD-L1) within the stromal compartment of gastric adenocarcinomas (GC). This study showed that PD-L1 is rather expressed by stromal than neoplastic cells and primarily at the tumour margin of PD-L1positive GC. Moreover, they identified a high proportion of CD8+ T cells within these areas that, in contrast to previous studies, correlated with worse progression-free survival and overall survival.1 We fully agree with their findings because of very similar results obtained regarding PD-L1 expression in a well-characterised cohort of pancreatic ductal adenocarcinomas (PDAC).2 Immunohistochemical PD-L1 staining revealed marked PD-L1 expression in 17 of 59 cases (30.4%) (figure 1A). Furthermore, pan-cytokeratin/PD-L1 costainings validated that in 76.5% of the PD-L1positive subgroup PD-L1 is predominantly or exclusively expressed …
Exploration of the potential of N-(4-hydroxyphenyl) retinamide (4-HPR) for induction of both differentiation and apoptosis in two human malignant glioblastoma cell lines T98G and U87MG
Authors: Arabinda Das, Surajit Karmakar, Sunil J. Patel, Naren L. Banik, Swapan K. Ray
Journal: Cancer Research (2005)

655  Retinoids have been shown to regulate vital cellular processes including cell proliferation, differentiation, and apoptosis. Fenretinide or N-(4-hydroxyphenyl) retinamide (4-HPR) is a synthetic retinoid that has shown minimal side effects in humans. It has biological activity against several malignancies, including leukemia and neuroblastoma in cell culture models. The efficacy of 4-HPR as a chemotherapeutic agent has also been demonstrated in animal models of mammary and prostatic tumors. Moreover, evaluation of 4-HPR action in several clinical trials appears to indicate a role for 4-HPR in controlling the growth of various malignancies in humans. Clinically achievable plasma concentrations of 4-HPR ranging from 1 to 3 μM have been shown to be well-tolerated in patients on clinical trial. More studies are being currently conducted to clarify a role for 4-HPR in controlling some malignancies. Glioblastoma is a highly malignant brain cancer that remains mostly refractory to the action of many chemotherapeutic agents. To explore the mechanisms underlying the chemotherapeutic effects of 4-HPR in human glioblastoma, we used two human glioblastoma cell lines T98G and U87MG. Trypan blue dye exclusion test showed that 4-HPR in a dose-dependent manner decreased the number of viable human glioblastoma cells. In situ methylene blue staining detected the morphological features of differentiated human glioblastoma cells following exposure to 1 μM and 2 μM HPR for 24 h. We applied the telomerase repeat amplification protocol (TRAP) to 4-HPR treated glioblastoma cells to determine a decrease in the activity of telomerase, an enzyme responsible for lending the unlimited capability of proliferation to the cancers including glioblastomas. Wright staining indicated predominantly apoptotic features in human glioblastoma cells following exposure to 1 μM and 2 μM 4-HPR for 72 h. Apoptosis in human glioblastoma cells was associated with an increase in intracellular free Ca2+, as determined by fura-2 assay. Western blot analyses showed alterations in the levels of expression of Bax and Bcl-2 proteins resulting in an increase in Bax:Bcl-2 ratio, and overexpression of calpain and caspase-3 that were also activated to cleave 270 kD α-spectrin at the specific sites for generation of 145 kD and 120 kD spectrin break down products (SBDPs), repectively, during apoptosis. Activation of caspase-3 was also confirmed by a colorimetric assay. Taken together, these results strongly suggest that 4-HPR can be used for induction of both differentiation and apoptosis in human glioblastoma cells. The efficacy of 4-HPR further needs to be evaluated in xenografted and allografted animal models of glioblastoma. The current investigation was supported in part by the R01 grants from the NCI and NINDS of the NIH (Bethesda, MD), and also a grant from the State of SC.
In vivo imaging of DR5 targeted therapy for breast cancer metastasis to bone
Authors: April Szafran, Diptiman Chanda, Kurt Zinn
Journal: Cancer Research (2007)

2403   Background. Bone metastases are present in nearly 85% of patients with late stage breast cancer and this disease manifestation results in significant morbidity. Novel therapeutic antibodies targeting death receptor 5 (DR5) expressed on tumors cells are in development to specifically target and kill malignant cell types. UAB has developed a DR5-targeted antibody called mTRA8, with proven efficacy to decrease primary tumor burden in animal models of breast cancer, but mTRA8 has not been evaluated in metastatic bone models. The current study tested mTRA-8 in combination with the anti-resorptive drug Zoledronic Acid (ZOL) as a therapy for breast cancer lesions in bone. Methods. Female athymic nude mice (4 weeks of age) were implanted in the tibia with 100,000 Luciferase Positive MDA-MB-231 breast cancer cells (Xenogen). Based on bioluminescence imaging, mice were randomized into 4 treatment groups (n=8/group): Saline, mTRA-8, mTRA-8 + ZOL, and ZOL. Bioluminescence images were acquired weekly to determine tumor burden non-invasively. Serum levels of TRAB-5b, a marker of increased osteolysis, as well as histomorphometric analyses are currently being performed on samples taken from these animals as independent measures of tumor burden. Results. Bioluminescence imaging detected differences in tumor growth according to treatment. All therapy groups provided a significant attenuation of tumor growth in comparison to saline treated controls. There was an approximate 10-fold or greater difference between saline treated controls and the mTRA-8 and Zoledronic Acid only groups; the mTRA-8 in combination with Zoledronic Acid group was significantly better than other treatments at week 5 after therapy start (p
BRD4 Profiling Identifies Critical Chronic Lymphocytic Leukemia Oncogenic Circuits and Reveals Sensitivity to PLX51107, a Novel Structurally Distinct BET Inhibitor
Authors: Hatice Gulcin Ozer, Dalia El-Gamal, Ben Powell, Zachary A. Hing, James S. Blachly, Bonnie Harrington, Shaneice Mitchell, Nicole R. Grieselhuber, Katie Williams, Tzung-Huei Lai, Lapo Alinari, Robert A. Baiocchi, Lindsey Brinton, Elizabeth Baskin, Matthew Cannon, Larry Beaver, Virginia M. Goettl, David M. Lucas, Jennifer A. Woyach, Deepa Sampath, Amy M. Lehman, Lianbo Yu, Jiazhong Zhang, Yan Ma, Ying Zhang, Wayne Spevak, Songyuan Shi, Paul Severson, Rafe Shellooe, Heidi Carias, Garson Tsang, Ken Dong, Todd Ewing, Adhirai Marimuthu, Christina Tantoy, Jason Walters, Laura Sanftner, Hamid Rezaei, Marika Nespi, Bernice Matusow, Gaston Habets, Prabha Ibrahim, Chao Zhang, Ewy A. Mathé, Gideon Bollag, John C. Byrd, Rosa Lapalombella
Journal: Cancer Discovery (2018)

Bromodomain and extra-terminal (BET) family proteins are key regulators of gene expression in cancer. Herein, we utilize BRD4 profiling to identify critical pathways involved in pathogenesis of chronic lymphocytic leukemia (CLL). BRD4 is overexpressed in CLL and is enriched proximal to genes upregulated or de novo expressed in CLL with known functions in disease pathogenesis and progression. These genes, including key members of the B-cell receptor (BCR) signaling pathway, provide a rationale for this therapeutic approach to identify new targets in alternative types of cancer. Additionally, we describe PLX51107, a structurally distinct BET inhibitor with novel in vitro and in vivo pharmacologic properties that emulates or exceeds the efficacy of BCR signaling agents in preclinical models of CLL. Herein, the discovery of the involvement of BRD4 in the core CLL transcriptional program provides a compelling rationale for clinical investigation of PLX51107 as epigenetic therapy in CLL and application of BRD4 profiling in other cancers.Significance: To date, functional studies of BRD4 in CLL are lacking. Through integrated genomic, functional, and pharmacologic analyses, we uncover the existence of BRD4-regulated core CLL transcriptional programs and present preclinical proof-of-concept studies validating BET inhibition as an epigenetic approach to target BCR signaling in CLL. Cancer Discov; 8(4); 458-77. ©2018 AACR.This article is highlighted in the In This Issue feature, p. 371.
Anhydramnios in Patients With Pemphigoid Gestationis
Authors: Garima Dabas, T. P. Afra, Dipankar De, Rahul Mahajan, Sanjeev Handa, Aashima Arora, Debajyoti Chatterjee
Journal: JAMA Dermatology (2018)

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Response to: ‘Can we prescribe TMP/SMX prophylaxis without any concerns equally for all patients with rheumatic disease?’ by Suyama and Okada
Authors: Jun Won Park, Jeffrey R Curtis, Eun Bong Lee
Journal: Annals of the Rheumatic Diseases (2018)

We deeply appreciate the comments by Suyama and Okada on our recent report regarding efficacy and safety of primary prophylaxis for pneumocystis pneumonia (PCP) using trimethoprim-sulfamethoxazole (TMP-SMX) in patients with rheumatic disease receiving prolonged, high-dose glucocorticoid treatment. 1 2They pointed out the possibility that patients with systemic lupus erythematosus (SLE) could have higher risk for adverse events related to TMP-SMX.They also indicated that discontinuation due to adverse events can be lowered by a graded administration strategy.In our cohort, the incidence rate of overall adverse drug reactions (ADR) was numerically higher in patients with SLE as compared with those with other rheumatic diseases, which is in line with the comment by Suyama and Okada (27.8 vs 16.6 per 100 person-years; incidence rate ratio 1.63, 95% CI 0.84 to 3.14).However, all ADRs in our SLE subgroup were mild to moderate in severity, and did not require urgent intervention or immediate discontinuation of TMP-SMX prophylaxis.Various clinical factors such as patient's ethnicity, concomitant medications or underlying rheumatic diseases can affect the frequency and seriousness of adverse events.However, we would like to remind that the previous studies reporting high adverse event rate of sulfa-antibiotics, which Suyama and Okada cited, were case-control studies and that most of the information was obtained by survey. [3]4][5] In addition, there were no data on the severity of the adverse events.Considering high mortality and morbidity of PCP in rheumatic diseases, the risk benefit of TMP-SMX prophylaxis should be estimated by the incidence of adverse events and by their severity.There remain many issues that need to be addressed before making a universal recommendation for primary PCP prophylaxis in patients with rheumatic diseases receiving high-dose glucocorticoids.An evidence-based, protocolised approach may be the first step.Establishment of the risk-benefit ratio of PCP prophylaxis for specific rheumatic diseases could then be a logical next step, as Suyama and Okada suggested, and we thank them for their important comment.
Endothelial JAK2 does not enhance liver lesions in mice with Budd-Chiari syndrome
Authors: Johanne Poisson, Moira B. Hilscher, Marion Tanguy, Adel Hammoutene, Chantal M. Boulanger, Jean-Luc Villeval, Douglas A. Simonetto, Dominique Valla, Vijay H. Shah, Pierre-Emmanuel Rautou
Journal: Journal of Hepatology (2018)
Real-world Study Characterizing Patients Prior to Receiving Albuterol Multidose Dry Powder Inhaler or Short-acting β 2 -Agonist Via Pressurized Metered-Dose Inhalers for Asthma and COPD in the United States
Authors: Gregory Bensch, Emily D. Parker, Rinat Ariely, Stanislav Stoyanov, Karthik Ramakrishnan
Journal: Journal of Allergy and Clinical Immunology (2018)
Allele-Specific Chromatin Recruitment and Therapeutic Vulnerabilities of ESR1 Activating Mutations
Authors: Rinath Jeselsohn, Johann S. Bergholz, Matthew Pun, MacIntosh Cornwell, Weihan Liu, Agostina Nardone, Tengfei Xiao, Wei Li, Xintao Qiu, Gilles Buchwalter, Ariel Feiglin, Kayley Abell-Hart, Teng Fei, Prakash Rao, Henry Long, Nicholas Kwiatkowski, Tinghu Zhang, Nathanael Gray, Diane Melchers, Rene Houtman, X. Shirley Liu, Ofir Cohen, Nikhil Wagle, Eric P. Winer, Jean Zhao, Myles Brown
Journal: Cancer Cell (2018)
Endosonography-guided hepatogastrostomy post-percutaneous biliary drainage in collaboration with interventional radiology
Authors: Ahmad Hashim, Yen-I Chen, David Valenti, Peter Metrakos, Sheryl White, Alan Barkun, Ali Bessissow
Journal: Endoscopy (2018)

Endoscopic ultrasonography-guided hepatogastrostomy (EUS-HGS) is an effective endoscopic modality for biliary drainage in the setting of concomitant gastric outlet obstruction [1] [2]. EUS-HGS however requires a dilated biliary system for technical success. This case report describes the first conversion of a percutaneous transhepatic biliary drain (PTBD) into an HGS in a non-dilated biliary system using EUS and interventional radiology techniques.