tbuckley/cabot-search huggingface dataset:
Toward the need to discriminate types of attackers and defenders in intergroup conflicts
Authors: Dashalini Katna, Bobby K Cheon
Journal: Behavioral and Brain Sciences (2019)

Abstract Here, we argue that attackers in intergroup conflicts are also likely to hold strong identity fusion, anticipate threat from the out-groups, and retaliate by signaling preemptive aggressiveness, which may not be asymmetrically exclusive to defenders. We propose that the study of the intergroup and intragroup dynamics could highlight more specific, robust markers to differentiate types of defenders from attackers.
Bi-monthly hepatic arterial infusion chemotherapy as a novel strategy for advanced hepatocellular carcinoma in decompensated cirrhotic patients
Authors: Kei Moriya, Tadashi Namisaki, Shinya Sato, Masanori Furukawa, Akitoshi Douhara, Hideto Kawaratani, Kosuke Kaji, Naotaka Shimozato, Yasuhiko Sawada, Soichiro Saikawa, Hiroaki Takaya, Koh Kitagawa, Takemi Akahane, Akira Mitoro, Junichi Yamao, Hitoshi Yoshiji
Journal: Clinical and Molecular Hepatology (2019)

We previously reported the comparable efficacy of bi-monthly hepatic arterial infusion chemotherapy (B-HAIC) to that of sorafenib chemotherapy for the treatment of advanced hepatocellular carcinoma (aHCC) in patients with compensated cirrhosis. In this study, we demonstrate the efficacy of B-HAIC in patients with decompensated cirrhosis.Forty-five patients with aHCC refractory to transcatheter arterial chemo-embolization (TACE) were treated with B-HAIC and were divided into two groups according to hepatic functional reserve (Child-Pugh grade). Overall survival period, treatment response, and adverse events in each group were analyzed.Efficacy and disease control rates in the Child-Pugh B group (n=24; 21% and 71%, respectively) were not significantly impaired compared the Child-Pugh A group (n=21; 38% and 67%, respectively). Median survival time and survival rate at 12 months in the Child-Pugh B group were 422 days and 58.3%, respectively, whereas those in the ChildPugh A group were 567 days and 70.8%, respectively. Importantly, the hepatic functional reserve of patients did not worsen in either group during the treatment period. Furthermore, the occurrence rate of adverse events leading to discontinuation of anti-tumor treatment was not significantly increased in the Child-Pugh B group.Given the preservation of hepatic functional reserve afforded by B-HAIC chemotherapy in patients with decompensated cirrhosis, B-HAIC might be an acceptable alternative strategy for aHCC patients who do not respond to TACE.
Aberrant CpG island hypermethylation of multiple genes in human prostate cancer
Authors: Mitali Pandey, Sanjay Gupta
Journal: Cancer Research (2007)

1058  Transcriptional silencing associated with aberrant promoter methylation has been established as an alternative pathway for development and progression of several human malignancies including prostate cancer. Identification of genes having cancer-specific CpG methylation may be indicative of disease process and could be developed as tumor marker. In this study we analyzed promoter methylation of some novel genes in human prostate cancer cells. Using TransSignal Methylation Array (Panomics, Redwood City, CA), we probed for DNA methylation in the genomes of androgen-responsive 22Rv1 and LNCaP and in androgen-refractory PC3 and DU145 human prostate cancer cell lines, representing various stages of disease progression and compared with normal prostate epithelial (PrEC) cells. Additionally, cell lines were probed for chemical response to demethylating agent 5’-aza-2’deoxycytidine by MS-PCR. RT-PCR and Western blotting was also performed for gene expression. Of the 82 gene promoter sequences probed on the array, 14 genes exhibited varying degree of promoter hypermethylation in various prostate cancer cell lines. Normal prostate epithelial cells did not exhibit promoter methylation. These genes include i) tumor suppressor genes: caspase-8, maspin, NME2, trefoil factor 1 and von-Hippel Lindau, ii) endotoxin receptor: CD14, iii) immunomodulatory cytokine: interleukin-4, iv) inhibitor of apoptosis: survivin, v) antiviral transcription factor: interferon regulatory factor-7, vii) proto-oncogene: MYC L2, viii) hormone receptor: platelet derived growth factor-beta, ix) replication protein A2, and x) microfilament proteins: trophinin associated protein: tastin and nestin. A closer examination of the 5’-upstream region of these genes revealed the presence of multiple CpG islands although all of them may not necessarily correlate with gene silencing. To further confirm the correlation between gene silencing and CpG methylation, we designed primers specific for proximal promoter region of these genes and performed MS-PCR before and after treatment with the 5’-aza-2’deoxycytidine. Absence of gene expression at mRNA and protein levels correlated with CpG promoter hypermethylation and genes like CD14, nestin and IRF-7 were predominantly hypermethylated whereas the survivin, tastin and VHL genes had hemimethylated promoters observed in prostate cancer cells. Our study reports a new set of genes previously not known to be epigenetically silenced through promoter hypermethylation in prostate cancer.
Vascular endothelial growth factor protects hepatoma cells against oxidative stress-induced cell death
Authors: Shinji Osada, Yasuyuki Sugiyama
Journal: Cancer Research (2006)

1032  Background and Aim The aim of the present study was to examine coordination of the vascular endothelial growth factor (VEGF) and VEGF receptor (Flk-1) system and to study control of VEGF expression by oxidative stress, which is considered a model for chronic liver disease. Methods Cell viability was determined by test method with 3-[4, 5-dimethylthiazol-2-yl]-2, 5-dephenyl tetrazolium bromide (MTT). Expressions of cellular proteins were evaluated by Western blott analysis. Results The c-Met tyrosine phosphorylation in PLC/PRF/5 hepatoma cells was increased by treatment with 20 ng/ml Hepatocyte Growth Factor (HGF), and extracellular signal-regulated kinase (ERK) was also activated. Although Flk-1 was phosphorylated in response to VEGF (>50 ng/ml), phosphorylated ERK was not detected at these concentrations. 5.0 and 10 μM hydrogen peroxide (H2O2) caused cell death in a dose-dependent manner after 24 hours. Upon Western blott analysis at 1 hour with H2O2, rapid phosphorylation of both ERK1/2 and c-Jun NH2-terminal kinase (JNK) was observed. In first 6 hours, H2O2 induced cell death for 58.4±6.8%, whereas the presence of 100 ng/ml VEGF improved the survival rate to 77.2±4.2. VEGF significantly decreased H2O2-induced cell death after 12 hours, whereas HGF (20 ng/ml) did not have a similar effect. When cells were incubated with 5 μM H2O2, expression of VEGF protein was detected. Furthermore, H2O2-induced phosphorylation of ERK and JNK was also reduced by VEGF (100 ng/ml). In contrast, HGF did not induce phosphorylation of ERK and JNK. Conclusion Hepatoma cells might be able to survive under condition continuous oxidative stress through expression of VEGF.
Bent not Broken
Authors: Ruth Little
Journal: BMJ (2002)

Lauren Roche

Zymurgy Publishing, £6.99, pp 267

ISBN 1 903506 02 6

Rating: ![Graphic][1] ![Graphic][2] ![Graphic][3] ![Graphic][4] 

Most doctors I know entered medical school straight from school or after undergraduate study. New Zealander Lauren Roche had an unconventional path to become a doctor, which included stints as a stowaway, stripper, prostitute, and drug misuser. She describes this journey in her courageous autobiography, Bent not Broken. 

Roche begins her narrative with snippets and stories from her childhood. These reveal instability, poverty, and abuse. Her parents' marriage ended in …

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ABC of preterm birth : Care in the early newborn period
Authors: William McGuire, Peter Fowlie, Peter McEwan
Journal: BMJ (2005)

The first week after birth is a time of major metabolic and physiological adaptation for newborn infants. Preterm infants have to cope with additional stresses because most of their organ systems are immature or because of associated illnesses, such as congenital infection. Very preterm infants (<32 weeks' gestation) or ill infants often need intensive monitoring and support during this critical period of postnatal adaptation.

### Preterm infants are susceptible to heat and fluid loss because

Preterm infants are susceptible to heat and fluid loss, especially immediately after delivery and in the first few days after birth. Hypothermia is associated with increased morbidity and mortality. Trials in the 1950s showed that reducing heat loss improves survival for preterm and low birthweight infants. Measures to prevent cold stress should start immediately after delivery—for example, resuscitating newborns under radiant heaters, drying them, and wrapping them in warmed towels straight away. A randomised controlled trial showed that wrapping the infant in polyethylene immediately (without drying) is at least as effective in reducing evaporative heat loss in extremely preterm infants (<28 weeks' gestation).

### Risk factors for respiratory distress syndrome

Potential adverse consequences of hypothermia

After admission to the neonatal unit unnecessary oxygen and energy consumption must be minimised. Several options are available for nursing preterm infants in a neutral thermal environment. Bigger and more mature infants (weighing > 1800 g) can usually maintain their body temperatures in open cots with clothing (including a hat), covers, and possibly a heated mattress. Smaller and less mature …
Growth inhibitory effect of xanthorrhizol is associated with the induction of apoptosis and up-regulation of non-steroidal anti-inflammatory drug-activated gene expression in hct116 human colon cancer cells
Authors: You-Jin Kang, Hyen Joo Park, Hwa-Jin Chung, Hye-Young Min, Eun-Jung Park, Ji-Young Hong, Hak-Sun Lee, Si Kyeong Jo, Su-Hyun Song, Kwang-Kyun Park, Jae-Kwan Hwang, Won-Yoon Chung, Sang Kook Lee
Journal: Cancer Research (2008)

478  Xanthorrhizol is a sesquiterpenoid isolated from the rhizome of Curcuma xanthorrhiza (Zingiberaceae). In our previous studies, xanthorrhizol has been exhibited with several biological activities including the suppressions of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) expression, inhibition of cancer cell growth, and anti-metastatic effect in in vivo animal model. However, the exact mechanisms of the growth inhibitory effects of cancer cells were not fully elucidated yet. In the present study, we investigated the growth inhibitory effect of xanthorrhizol on cancer cells in points of cell cycle regulation and events of apoptosis in HCT116 human colon cancer cells. Primarily, treatment of xanthorrhizol exhibited the antiproliferative effects of HCT116 cells in a concentration-dependent manner. Flow cytometric analysis indicated that xanthorrhizol arrested cell cycle progression at G0/G1 and G2/M phase, and induced the increase of sub-G1 peaks in concentration- and time-dependent manners. Induction of cell cycle arrest was highly correlated with the downregulation of cyclins and cyclin dependent kinases such as cyclin A, cyclin B1, CDK2, CDK4 and also the induction of cyclin kinase inhibitors p21 and p27. The increase of sub-G1 peaks by xanthorrhizol was closely related to the induction of apoptosis, which was evidenced by the induction of DNA fragmentation, truncation of bid, inhibition of bcl-XL expression, increase of the release of cytochrome c from mitochondria, activation of caspase-3, -8 and -9, and cleavage of poly-(ADP-ribose) polymerase. Further study revealed that xanthorrhizol increased the expression and promoter activity of the pro-apoptotic protein non-steroidal anti-inflammatory activated gene (NAG-1), suggesting up-regulation of NAG-1 might in part be involved in the induction of apoptosis by xanthorrhizol. These findings provide one plausible mechanism in the growth inhibitory activity of xanthorrhizol against cancer cells by arresting cell cycle and induction of apoptosis, and thus it might be a potential lead candidate in the preventive and/or therapeutic point of human colon cancers.
The effects of parenteral prostacyclin therapy as add-on treatment to oral compounds in Eisenmenger syndrome
Authors: Michele D'Alto, Andrew Constantine, Olga Hajnalka Balint, Emanuele Romeo, Paola Argiento, Laszlo Ablonczy, Nika Skoro-Sajer, George Giannakoulas, Konstantinos Dimopoulos
Journal: European Respiratory Journal (2019)

<b>In this European cohort of Eisenmenger patients, prostanoid therapy, as part of triple combination therapy, was found to be safe and effective in improving exercise capacity, natriuretic peptide levels and haemodynamic parameters over a 2-year period</b>http://bit.ly/2Zl3W1Z
Effect of the green tea polyphenol epigallocatechin gallate (EGCG) on growth and IL-6 signalling pathways in malignant plasma cells
Authors: R. Burger, H. Czekalla, K. Richter, T. Ahrens, A. Guenther, M. Gramatzki
Journal: Journal of Clinical Oncology (2007)

8114 Background: Epigallocatechin gallate (EGCG) is the predominant polyphenolic constituent of green tea leaves that possesses antitumor, antiinflammatory, and antioxidant activity. EGCG exerts its effects through potentially multiple mechanisms including inhibition of growth factor receptor signalling. The compound is currently under investigation in a phase I/II clinical trial for treatment of patients with early stage chronic lymphocytic leukemia at Mayo Clinic. The goal of our study was to examine the in vitro effects of EGCG in multiple myeloma (MM). Methods: A panel of human myeloma cell lines (n=6) including the IL-6 dependent INA-6 cell line was used to evaluate the sensitivity to EGCG. Cells were cultured for three days in the absence or presence of EGCG at concentrations between 6.25 μM and 100 μM. Cell viability was determined in a colorimetric tetrazolium (MTS) based assay and by trypanblue exclusion. For signalling experiments, INA-6 cells were IL-6 and serum starved and then treated with EGCG for two hours before IL-6 was added. Whole cell lysates were prepared and subjected to SDS-PAGE and Western blot analysis. Results: EGCG inhibited the in vitro growth of human myeloma cell lines by inducing cell death in a time and dose-dependent manner. IC 50 concentrations were between 12,5 μM and 50 μM. IL-6 mediated growth of INA-6 cells was inhibited at similar doses. The addition of excess amounts of IL-6 could not protect from EGCG induced cytotoxicity. Pretreatment of INA-6 cells with EGCG resulted in a dose-dependent inhibition of IL-6 induced STAT3 tyrosine phosphorylation. In these cells, stimulation with IL-6 leads to upregulation of Mcl-1 expression. In contrast, phosphorylation of p44/p42 MAPK, which is constitutively activated in INA-6 cells, was not affected. Conclusion: EGCG has growth inhibitory activity on myeloma cells. Specific inhibition of signalling pathways that regulate expression of anti-apoptotic proteins could be one mechanism how EGCG exerts its activity. Our work provides the rationale for further studies to evaluate the effect of EGCG not only in B-CLL, but also in plasma cell tumors. No significant financial relationships to disclose.
Angiogenesis: Human Ocular Angiogenesis‐Inspired Vascular Models on an Injection‐Molded Microfluidic Chip (Adv. Healthcare Mater. 15/2019)
Authors: Jihoon Ko, Younggyun Lee, Somin Lee, Seung‐Ryeol Lee, Noo Li Jeon
Journal: Advanced Healthcare Materials (2019)

In article number 1900328, Noo Li Jeon and co-workers' work highlights engineered neovascular models inspired by ocular angiogenesis for drug screening with high throughput. The ready-to-use microfluidic platform enables functional and morphological vessel modeling based on a simple experimental approach and robust reproducible results. The well-established model can yield dose-dependent responses for anti-angiogenic drugs. This model has the potential to replace the ocular angiogenesis assay performed in animal experiments.
A Novel Educational Intervention for Chronic Viral Hepatitis (CVH) Case-Finding in UK South-Asians, a High-Risk Population: Preliminary Results from a National Institute for Health Research (NIHR) Feasibility Study
Authors: C Kelly, M Pericleous, A Ahmed, J Hendy, T Vandrevala, S Mathew, S De Lusignan, A Ala
Journal: Hepatology (2018)
High throughput, highly multiplexed transcriptional profiling of cytologic preparations from buccal mucosa
Authors: R. B. Everson, D. Bangsi, L. L. Darga, M. R. Bell, V. P. Pidlaoan, D. Kanakapalli
Journal: Journal of Clinical Oncology (2007)

14104 Background: Alterations in gene expression can be sensitive and informative indicators that a biologically effective exposure occurred. For example, serial specimens could provide evidence that a dose with a biological effect was reached in Phase I testing. Sampling buccal mucosal can provide epithelial cell specimens rapidly with little discomfort. However, ribonucleases in saliva rapidly degrade epithelial cell RNA, prohibiting analysis by standard array techniques. Using buccal cells, we conducted a pilot study to optimize procedures for RNA isolation and analysis and determined influences of gender, race, and cigarette smoking on gene expression. Methods: Buccal cells were collected by scraping the inner cheek with a previously described standardized plastic tool (BioTechniques. 2004;36:484–487) made available Avrum Spira of Boston University. Preliminary experiments compared RNA extraction procedures, including methods based on trizol (Invitrogen, Carlsbad, CA), RNeasy columns (Qiagen, Valencia, CA), and the High Pure RNA Paraffin Kit (Roche, Indiana, USA). After standardization of the method, specimens were obtained from 64 subjects using a blocked design sampling equal numbers of subjects by gender, African American and white race, and smoking status. Gene expression levels were determined using the cDNA-mediated annealing, selection, extension, and ligation assay (Illumina, Inc.), which measures expression of over 500 genes per analysis. Results: The Roche extraction method provided the highest yield of RNA and was used for subsequent assays. Technical replicates were highly reproducible. Preliminary analyses revealed that using P=0.05, 38 genes were expressed differentially by gender, 20 by race, and 10 by smoking status. The genes most differentially expressed by gender included IRF1, MET, STAT1, RAP1GDS1; race CD9, CCNA2, CEACAM1, FVT1; smoking CD44, NQO1, SKI, SRC. Conclusions: Highly multiplexed gene expression analysis of buccal cells are feasible. Demographic characteristics of study subjects can be important, but they do not heavily influence levels for many genes. Results indicate the assays could be provide useful information in cross-sectional or serial studies of the impact of molecular therapeutics. No significant financial relationships to disclose.
Inhibition of DOT1L and PRMT5 Promotes Anti-Tumor Activity in a Human MLL Leukemia Model Induced By CRISPR/Cas9
Authors: Kathy-Ann Secker, Hildegard Keppeler, Silke Duerr-Stoerzer, Hannes Schmid, Dominik Schneidawind, Thomas Hentrich, Julia Schulze-Hentrich, Barbara Mankel, Falko Fend, Lothar Kanz, Corina Schneidawind
Journal: Blood (2018)
Alkaline phosphatase normalization is associated with a decreased risk for liver transplantation and death in patients with primary biliary cholangitis
Authors: Carla Fiorella Murillo Perez, Aliya Gulamhusein, Christophe Corpechot, Adriaan Van der Meer, Henk R Van Buuren, Pietro Invernizzi, Palak Trivedi, Frederik Nevens, Marlyn J Mayo, Pier Maria Battezzati, Willem J Lammers, Annarosa Floreani, Albert Pares, Marco Carbone, Kris Kowdley, Tony Bruns, Jorn C Goet, Cyriel Y Ponsioen, George N Dalekos, Douglas Thorburn, Andrew Mason, Nicholas F LaRusso, Nikolaos K Gatselis, Raoul Poupon, Xavier Verhelst, Keith D Lindor, Harry La Janssen, Gideon Hirschfield, Bettina E Hansen
Journal: Hepatology (2018)
Acalabrutinib with Obinutuzumab in Relapsed/Refractory and Treatment-Naive Patients with Chronic Lymphocytic Leukemia: The Phase 1b/2 ACE-CL-003 Study
Authors: Jennifer A. Woyach, Farrukh T. Awan, Mojgan Jianfar, Kerry A. Rogers, Jeffrey Jones, Todd Covey, Ahmed Hamdy, Raquel Izumi, Priti Patel, Min Hui Wang, John C. Byrd
Journal: Blood (2017)
ADTH-05 Percutaneous transhepatic cholangioscopy in the treatment of biliary ductal stones
Authors: George Goodchild, Jonathan Potts, Nick Burr, Margaret G Keane, Michael H Chapman, Gavin J Johnson, Stephen P Pereira, Matt Huggett, George J Webster
Journal: Endoscopy (2018)

<h3>Introduction</h3> Percutaneous direct cholangioscopy may expand diagnostic and treatment options where endoscopic biliary access is precluded by post-surgical anatomy. We aim to report the utility of percutaneous transhepatic cholangioscopy in patients with intrahepatic stone disease, using the SpyGlass DS cholangioscopy system. <h3>Methods</h3> Five patients underwent percutaneous cholangioscopy between July '17 and February '18. All had post-surgical duodenal anatomy and intrahepatic duct (IHD) stones, three with an associated anastomotic stricture. In all cases prior percutaneous transhepatic cholangiography (PTC) and biliary access was achieved using conventional interventional radiology techniques, with the transhepatic tract dilated to 12 F, and a drain left <i>in situ</i>. <h3>Results</h3> The procedures are summarised in Table 1. Five procedures were performed under general anaesthetic and one with sedation, with the patient supine. All patients received antibiotic prophylaxis. Under sterile conditions the cholangioscope was introduced percutaneously into the intrahepatic biliary tree via a peel-away sheath (12Fr in 5 cases and 11Fr in 1). Optimal stone localisation was achieved using fluoroscopy and direct visualisation, allowing application of electrohydraulic lithotripsy (EHL) using a Boston Scientific EHL probe for stone fragmentation. In one case 8 mm-10 mm sequential dilatation of an anastomotic stricture was performed. In one case a surgical stitch across the anastomosis was visualised – the likely nidus for stone formation. Stone clearance was successful in all cases where IHD stones were identified. In one case the IHD stones had cleared since the index PTC. There were no recorded procedural complications. <h3>Conclusion</h3> In this small case series direct visualisation of the biliary tree using percutaneous SpyGlass cholangioscopy was safe, successful and expanded the therapeutic capabilities of PTC. This technique could also be used to enhance the investigation and treatment of post-surgical biliary anastomotic stricturing, where retrograde endoscopic access is not feasible.