tbuckley/cabot-search huggingface dataset:
Biodegradable coronary scaffolds: their future and clinical and technological challenges
Authors: Jarkko P Hytönen, Jouni Taavitsainen, Santeri Tarvainen, Seppo Ylä-Herttuala
Journal: Cardiovascular Research (2018)

Angioplasty and stenting are standard treatment options for both stabile occlusive coronary artery disease and acute myocardial infarctions. Over the last years, several biodegradable stent systems have entered pre-clinical and clinical evaluation and into clinical practice. A strong supporting scaffold is necessary after angioplasty to prevent elastic recoil of the vessel but in the long term a permanent metallic stent will only impair normal physiology of the artery wall. Thus, the main advantage of a resorbable system is the potential for better vessel recovery and function in the long term. The new stent systems differ from traditional stents in size and biological responses and questions have risen regarding their mechanical strength and increased risk of stent thrombosis. Here, we present current treatment options with biodegradable scaffolds, discuss further key areas for improvements and review novel technological advances in the context of all up-to-date clinical trial information. New material choices are also covered as well as special considerations for pre-clinical testing.
Symptoms at lung cancer diagnosis are associated with major differences in prognosis
Authors: Victoria L Athey, Stephen J Walters, Trevor K Rogers
Journal: Thorax (2018)

We report a cohort study of survival of patients with lung cancer presenting to a single multidisciplinary team between 1997 and 2011, according to symptoms at presentation. The overall median survival of the 3800 lung cases was 183 days (95% CI 171 to 195). There was a statistically significant difference in survival between the 12 symptom groups identified both without and with adjustment for the prognostic variables of age, gender and histology (P<0.001). Compared with the cough-alone symptom group, the risks of dying or HRs were significantly higher for the groups presenting with breathlessness (HR 1.86, 95% CI 1.54 to 2.24, n=359), systemic symptoms (HR 1.91, 95% CI 1.48 to 2.45, n=95), weight loss (HR 2.46, 95% CI 1.90 to 3.18, n=106), chest pain (HR 1.96, 95% CI 1.56 to 2.45, n=159), cough with breathlessness (HR 1.59 95% CI 1.28 to 1.98, n=177), neurological symptoms (HR 3.07, 95% CI 2.45 to 3.84, n=155) and other symptom combinations (HR 2.05, 95% CI 1.75 to 2.40, n=1963). Cough may deserve particular prominence in public health campaigns.
Impact of the alpha-Fetoprotein model for patient selection for Liver Transplantation for Hepatocellular Carcinoma, a French experience
Authors: B. Brusset, Q.J. Louis, J. Dumortier, D. Cherqui, G.-P. Pageaux, S. Dharancy, S. Radenne, D. Samuel, D. Thomas
Journal: Journal of Hepatology (2018)
Abstract 14527: MicroRNAs Are Novel Plasma Biomarkers for Diagnosis and Prognosis of Abdominal Aortic Aneurysm Disease
Authors: Ekaterina Chernogubova, Suzanne M Eken, Joshua M Spin, Uwe Raaz, Hong Jin, Joy Roy, Anders Hamsten, Per Eriksson, Philip S Tsao, Lars Maegdefessel
Journal: Circulation (2013)

MicroRNAs (miRNAs) have been identified as posttranscriptional inhibitors of gene expression, thought to “fine tune” the translational output of their target mRNAs. Recently, they have received much attention regarding their suitability as biomarkers for disease. Aim of this current study was to explore the diagnostic and prognostic value of miRNAs in abdominal aortic aneurysms (AAAs), a disease for which currently no established biomarker exists.  Using a PCR-based array platform, we profiled the 168 most abundant blood miRNAs in 20 patient plasma samples with AAA disease, undergoing surgical repair of their enlarged aorta vs. 20 samples from an age, risk factor, and medication matched screening cohort without aneurysm. We were able to identify a total number of 12 miRNAs that were significantly altered in diseased patient samples as compared to controls. We further investigated these 12 miRNAs in plasma (as well as in aortic tissue) from apoE-/- mice with angiotensinII (AngII)-infusion induced AAAs, in order to determine the potential prognostic value of miRNAs being released into circulation. Indeed we were able to detect that the expression of 4 out of the 12 miRNAs (miRs-126 and -668 both increased; miRs-24 and -210 both decreased), was substantially altered in plasma samples drawn from AAA mice immediately before rupture occurred between days 7 and 14 after AngII pump implantation compared to mice with AAA that did not rupture for the remainder of study (28 days), as well as saline-infused controls. Importantly, the expression of miRs-24 and -126 were also significantly different in plasma samples from patients with ruptured AAAs (n=7) compared to patients with non-ruptured AAAs (abdominal aortic diameter between 55-78 mm; n=7) and undiseased controls (n=7).  The present study explores the diagnostic and prognostic biomarker potential of miRNAs being released into circulation during initiation, propagation, and ultimately rupture of AAA disease in mice and humans. The identification of miRs-24, -126, -210, and -668 potentially offers great prognostic value to determine which patients present with increased risk of AAA rupture.
Effects of direct-acting antiviral treatment of chronic hepatitis C on macrophage activation, liver stiffness, metabolic liver function and portal hypertension in cirrhosis patients
Authors: T.L. Laursen, K. Kazankov, T.D. Sandahl, H.J. Møller, L. Hagelskjær Kristensen, C. Holmboe, C. Sølund, H. Arildsen, A. Laursen, H. Grønbæk
Journal: Journal of Hepatology (2018)
When you live with a degenerative illness, no symptoms are mild
Authors: Beth McHugh
Journal: BMJ (2018)

When you live with a degenerative illness, no symptoms are mildComparing a patient's symptoms to those who are worse off can be far from reassuring, says Beth McHugh Beth McHughI was first given a diagnosis of relapsing remitting multiple sclerosis in my 20s.Four years later, a string of relapses triggered involuntary movements in my arms and legs, and I had pain, visual problems, and debilitating fatigue.When my symptoms were at their peak, I couldn't work as a writer and artist.I couldn't cook for myself, hold my own drinks, or shower without someone in the house.Eventually I had to move back in with my parents.This was devastating, and I felt as if all my worst fears about my illness were coming true.
P540Assessment of cardioprotective properties of FSTL1 in vitro using human iPSC-derived cardiomyocytes
Authors: K Neef, T Meijs, A Van Mil, I Van Adrichem, P Doevendans, J Sluijter, S Chamuleau
Journal: Cardiovascular Research (2018)

Background: Extracellular vesicles (EVs) derived from various cell-types are promising biomarkers for various diseases.They constitute a heterogeneous population ranging from 0.1 to 1 mm in size.Due to their small size and low expression levels, they are difficult to measure accurately with flow cytometry.Aim: To design a high-sensitive assay for platelet-derived and tissue factor (TF) positive EVs in plasma based on dual antibody recognition and the solid-phase proximity ligation assay (SP-PLA) technique.Method: Lactadherin (binds to phosphatidylserine) and cholera toxin subunit B (CT-B, binds to ganglioside) were used to capture different types of EVs.Detection antibodies were conjugated with either of two oligonucleotides that are ligated and serve as a template for a qPCR reaction when antibodies are bound in proximity.We compared the results with high-sensitivity flow cytometry (platelet-derived) and a direct coagulation activity assay (TF-positive EVs).Results: We demonstrate that platelet-derived EVs in plasma can be measured using SP-PLA with high sensitivity and specificity.The results correlate with high-sensitivity flow cytometry (Pearson R¼ 0.65 p<0.0001), with the difference that SP-PLA detects EVs also after filtration with a 0.2 mm filter, showing that also smaller EVs are detected.The assay, using CT-B or lactadherin as capture agents, furthermore allowed detection of the more rare population of TFþ EVs.Upon spike-in with relipidated TF, the SP-PLA for TFþEVs captured by lactadherin had a detection range of at least 4 logs and a Limit of Detection (LoD) score of 0.5 pg/ml.Conclusions: These results demonstrate that different populations of cell-derived EVs can be detected sensitively with SP-PLA and that also the smaller EVs can be measured accurately.The SP-PLA technique is thereby a suitable tool for measuring EVs in plasma, and may prove useful when studying the role of EVs in several complex diseases. P539Autologous myeloid cells restore the augmented vascular smooth muscle tone under high glucose concentration
Comparative risk of major congenital malformations with eight different antiepileptic drugs: a prospective cohort study of the EURAP registry
Authors: Torbjörn Tomson, Dina Battino, Erminio Bonizzoni, John Craig, Dick Lindhout, Emilio Perucca, Anne Sabers, Sanjeev V Thomas, Frank Vajda, Francesca Faravelli, Chiara Pantaleoni, Elisabeth Robert-Gnansia, Leonor Cabral-Lim, Boštjan Čebular, Alejandro De Marinis, Reetta Kälviäinen, Ketevan Khomeriki, Gordana Kiteva-Trencevska, Silvia Kochen, Martin Kurthen, Gerhard Luef, Meritxell Martinez Ferri, Maja Milovanović, Karl Otto Nakken, Miri Neufeld, Hideyuki Ohtani, Aline Russell, Vladimír Safcák, Bettina Schmitz, Luigi Maria Specchio, Barbara Tettenborn, Eugene van Puijenbroek, Hsiang-Yu Yu, Jana Zarubova, Claus Albretsen, Silje Alvestad, Noemi Becser Andersen, Luisa Antonini, Jens Arentsen, Dag Aurlien, Ismael Barzinji, Juan Luis Becerra Cuñat, Natalia Bohorquez Morera, Martin J. Brodie, Eylert Brodtkorb, Laura Broglio, Elsebeth Bruun Christensen, Petr Bušek, Claudia Cagnetti, Maria Paola Canevini, Astrid Carius, Maria Dolores Castro Vilanova, Michela Cecconi, T-Y Chang, Jakob Christensen, Giovanni De Maria, Dieter Dennig, Brenda Diputado, Janne Marit Ertresvåg, Toni Escartin, Dominique Flügel, Birgitte Forsom Sondal, Nicoletta Foschi, Albertina Franza, Katsuyuki Fukushima, Antonio Gambardella, Iñigo Garamendi Ruiz, Helena Gauffin, Pia Gellert, Leif Gjerstad, Lisa Gordon, Katrine Haggag, Imad Halawa, Terttu Heikinheimo-Connell, Tim Hendgen, Zarouhi Hertz, Odo Hildenhagen, Stephanie Hödl, Ineke Hogenesch, Anette Huuse Farmen, Yushi Inoue, Stefan Juhl, Masaaki Kato, Germaine Kenou Van Rijckevorssel, E. Kluck, Hana Krijtová, Eva Kumlien, Angelo Labate, Theresa Lasch, Hans Lindsten, Renata Listonova, Rasmus Lossius, Anders Lundgren, Kristina Malmgren, Iva Marečková, Daniela Marino, Peter Mattsson, Aileen McGonigal, Katarzyna Miesczanleh, Masahiro Mizobuchi, Barbara Mostacci, Birgit Müffelmann, Uden Navn, Anders Nilsson, Bernhard Oehl, Andrea Ortenzi, Judith Osseforth, Aldo Paggi, Eliana Pastor, Birthe Pedersen, Vaiva Petrenaite, Pietro Pignatta, Isabel Pires, Alessandra Pistelli, Jesús Antonio Riuz Gimenez, Raffaele Rocchi, Lone Rodam, Reina Roivainen, Gisela Rytířová, Christian Samsonsen, Gemma Sansa Fayos, Anna Maija Saukkonen, Alma Sikiric, David Sopelana Garay, Bernhard Steinhoff, Maria Strandberg, Torleiv Svendsen, Erik Tauboll, Kiyohito Terada, Marina Trivisano, Katherine Turner, Mogens Worm, Elias Zakharia, Elena Zambrelli, Morteza Zarifi-Oskoie
Journal: The Lancet Neurology (2018)
Hepatocellular Carcinoma Is Associated With Gut Microbiota Profile and Inflammation in Nonalcoholic Fatty Liver Disease
Authors: Francesca Romana Ponziani, Sherrie Bhoori, Chiara Castelli, Lorenza Putignani, Licia Rivoltini, Federica Del Chierico, Maurizio Sanguinetti, Daniele Morelli, Francesco Paroni Sterbini, Valentina Petito, Sofia Reddel, Riccardo Calvani, Chiara Camisaschi, Anna Picca, Alessandra Tuccitto, Antonio Gasbarrini, Maurizio Pompili, Vincenzo Mazzaferro
Journal: Hepatology (2018)

The gut-liver axis plays a pivotal role in the pathogenesis of nonalcoholic fatty liver disease (NAFLD), which is the third leading cause of hepatocellular carcinoma (HCC) worldwide. However, the link between gut microbiota and hepatocarcinogenesis remains to be clarified. The aim of this study was to explore what features of the gut microbiota are associated with HCC in patients with cirrhosis and NAFLD. A consecutive series of patients with NAFLD-related cirrhosis and HCC (group 1, 21 patients), NAFLD-related cirrhosis without HCC (group 2, 20 patients), and healthy controls (group 3, 20 patients) was studied for gut microbiota profile, intestinal permeability, inflammatory status, and circulating mononuclear cells. We finally constructed a model depicting the most relevant correlations among these features, possibly involved in hepatocarcinogenesis. Patients with HCC showed increased levels of fecal calprotectin, while intestinal permeability was similar to patients with cirrhosis but without HCC. Plasma levels of interleukin 8 (IL8), IL13, chemokine (C-C motif) ligand (CCL) 3, CCL4, and CCL5 were higher in the HCC group and associated with an activated status of circulating monocytes. The fecal microbiota of the whole group of patients with cirrhosis showed higher abundance of Enterobacteriaceae and Streptococcus and a reduction in Akkermansia. Bacteroides and Ruminococcaceae were increased in the HCC group, while Bifidobacterium was reduced. Akkermansia and Bifidobacterium were inversely correlated with calprotectin concentration, which in turn was associated with humoral and cellular inflammatory markers. A similar behavior was also observed for Bacteroides. Conclusion: Our results suggest that in patients with cirrhosis and NAFLD the gut microbiota profile and systemic inflammation are significantly correlated and can concur in the process of hepatocarcinogenesis.
Role of Molecular Profiling in Soft Tissue Sarcoma
Authors: Timothy Lindsay, Sujana Movva
Journal: Journal of the National Comprehensive Cancer Network (2018)

Diagnosis and treatment of soft tissue sarcoma (STS) is a particularly daunting task, largely due to the profound heterogeneity that characterizes these malignancies. Molecular profiling has emerged as a useful tool to confirm histologic diagnoses and more accurately classify these malignancies. Recent large-scale, multiplatform analyses have begun the work of establishing a more complete understanding of molecular profiling in STS subtypes and to identify new molecular alterations that may guide the development of novel targeted therapies. This review provides a brief and general overview of the role that molecular profiling has in STS, highlighting select sarcoma subtypes that are notable for recent developments. The role of molecular profiling as it relates to diagnostic strategies is discussed, along with ways that molecular profiling may provide guidance for potential therapeutic interventions.
Translating Immunology into Therapeutic Concepts for Inflammatory Bowel Disease
Authors: Holm H. Uhlig, Fiona Powrie
Journal: Annual Review of Immunology (2018)

Inflammatory bowel disease (IBD) defines a spectrum of complex disorders. Understanding how environmental risk factors, alterations of the intestinal microbiota, and polygenetic and epigenetic susceptibility impact on immune pathways is key for developing targeted therapies. Mechanistic understanding of polygenic IBD is complemented by Mendelian disorders that present with IBD, pharmacological interventions that cause colitis, autoimmunity, and multiple animal models. Collectively, this multifactorial pathogenesis supports a concept of immune checkpoints that control microbial-host interactions in the gut by modulating innate and adaptive immunity, as well as epithelial and mesenchymal cell responses. In addition to classical immunosuppressive strategies, we discuss how resetting the microbiota and restoring innate immune responses, in particular autophagy and epithelial barrier function, might be key for maintaining remission or preventing IBD. Targeting checkpoints in genetically stratified subgroups of patients with Mendelian disorder–associated IBD increasingly directs treatment strategies as part of personalized medicine.
Identification of actionable mutations in surgically resected tumor specimens from Japanese patients with non-small cell lung cancer by ultra-deep targeted sequencing.
Authors: Yasuhiro Koh, Hirotsugu Kenmotsu, Masakuni Serizawa, Mitsuhiro Isaka, Keita Mori, Hisao Imai, Hiroaki Akamatsu, Akira Ono, Tateaki Naito, Tetsuhiko Taira, Haruyasu Murakami, Toshiaki Takahashi, Masahiro Endo, Takashi Nakajima, Yasuhisa Ohde, Nobuyuki Yamamoto
Journal: Journal of Clinical Oncology (2013)

7572 Background: Detection of tumor genetic alterations is critically needed for lung cancer clinic as well as for the development of molecular targeted therapeutics. Here we report the results of a broad spectrum of genetic alterations identified in Japanese non-small cell lung cancer (NSCLC) patients by ultra-deep targeted sequencing. Methods: Highly multiplexed amplicon sequencing was performed using genomic DNA extracted from snap-frozen tumor specimens. TruSeq amplicon cancer panel was used for the detection of somatic mutations in 48 cancer related genes followed by ultra-deep sequencing (Illumina) at an average coverage of approximately 2800x. ALK, ROS1 and RET traslocations and EGFR, MET, PIK3CA, FGFR1 and FGFR2 amplifications were also detected by multiplex RT-PCR and quantitative PCR, respectively. Results: The demographics of 204 consecutive patients enrolled in this prospective study at Shizuoka Cancer Center between July 2011 and November 2012: median age 69 years (range: 38-92); male 66%; never smoker 25.5%; histology: adenocarcinoma 68.6%, squamous cell carcinoma (SQ) 27.0%, others 4.4%; tumor stage: I 53.9%, II 28.4%, III 12.7%, IV 4.9%. TP53 mutation was most frequently detected (44.4%) in all patients, particularly in SQ (67.9%). Mutations in genes such as MLH1 (4.9%), STK11 (6.3%), CTNNB1 (5.6%), SMAD4 (1.4%), VHL1 (1.4%), PTPN11 (0.7%) and GNAS (0.7%) were detected besides major mutations in genes such as EGFR (43.0%), KRAS (17.6%) and PIK3CA (14.1%) in adenocarcinoma. PIK3CA (21.4%), MLH1 (5.4%), APC (3.6%), STK11 (3.6%), FGFR2 (1.8%) and VHL (1.8%) mutations were identified in SQ and notably, 48.2% of SQ patients harbored simultaneous gene mutations, suggesting the genetic complexity of this histology. FGFR1 amplification was found in 8.9 % of SQ, suggesting lower frequency in Asian population than in Caucasian population. Conclusions: We managed to detect a wide range of genetic alterations and identified additional actionable mutations besides popular driver mutations. This approach may facilitate elucidation of detailed molecular characteristics of NSCLC, thereby implementing personalized cancer medicine.
Clare Searle: combines being a GP with obstetrics and gynaecology
Authors: Anne Gulland
Journal: BMJ (2018)

From the beginning of her career, Clare Searle was torn between general practice and obstetrics and gynaecology. She loved the patient contact and continuity of care that general practice could offer but she was also fascinated by gynaecology. After completing her vocational training scheme in general practice, she decided to explore obstetrics and gynaecology again.

“I was told that to become a consultant was an impossibly long and difficult path and that it would be extremely hard to juggle my time between family and career,” she says. “So, at 18 weeks pregnant, I made the decision to continue in general practice.”

Her return to general practice coincided with the growth in laparoscopic surgery, improved ultrasound techniques, and a push for more procedures to be delivered in primary care.

Having an undertaken an MSc in community gynaecology and reproductive healthcare, Searle launched a full …
Elongated Appearance of Meckel’s Diverticulum on 99mTcO4 Scintigraphy
Authors: Ha Wu, Ruifang Zhao, Zai Song, B.T. Kung, Xiaofei Zhao
Journal: Clinical Nuclear Medicine (2018)

A Meckel's scintigraphy using TcO4 was performed in a 9-year-old boy. The images revealed an elongated abnormal radiotracer accumulation in the right abdomen, which was confirmed as Meckel diverticulum combined with an omphalomesenteric cyst.
Human chorionic gonadotropin (HCG) induction of apoptosis in breast cancer
Authors: W. B. Carter, M. Sekharam
Journal: Journal of Clinical Oncology (2006)

10658 Background: Apoptotic induction in cancer cells may improve the efficacy of local or systemic therapy. Human Chorionic Gonadotropin (HCG) injection directly into Kaposi’s sarcoma or melanoma has been shown to increase the apoptotic index in these tumor types. The rapid induction of apoptosis in breast cancer immediately preceding local or systemic therapy may improve the response to therapy or local control. We hypothesized that HCG would rapidly increase the apoptotic index in breast cancer after intratumoral injection. The primary objective of this preclinical trial was to determine if intratumoral injection of HCG would significantly increase the apoptotic index in breast cancer xenografts. Methods: Using a human breast cancer xenograft model in Nude mice, 5 × 10 6 SK-BR3 human breast cancer cells were injected subcutaneously into each flank of nu/nu mice. When the tumors reached 6 mm, 50 uL (100 U/mL) of non-recombinant, naturally occuring HCG (A.P.L., Wyeth) or saline vehicle control was injected directly into the xenograft tumors. After 24 hrs, the tumors were harvested, and the xenografts tested for proliferation (Ki-67) and apoptosis (by TUNEL assay). The apoptotic index was calculated (apoptosis/proliferation) and statistical analysis performed using paired T-test. Results: Seven pairs of SK-Br3 xenografts were tested. There were no differences in proliferation by Ki-67 determination between control or treated xenografts. Apoptosis increased in HCG treated xenografts compared to vehicle controls. Apoptosis increased from a mean of 5% (range 1– 20%) in control xenografts to a mean of 28% (range 1–70%) in HCG treated tumors (p = 0.038). Conclusions: Naturally-derived HCG induces apoptosis in human breast cancer xenografts after intratumoral injection. Substantial induction of apoptosis may improve the efficacy of local and systemic therapy in breast cancer. Injection of HCG into breast tumors immediately prior to surgical, radiation, or systemic therapy has the potential to improve local control or response to treatment. Futher elucidation of potential synergy with therapeutic modalities is justified. No significant financial relationships to disclose.
Genomic sequence investigation Streptococcus pyogenes clusters in England (2010–2015)
Authors: J.M. Coelho, G. Kapatai, A. Jironkin, A. Al-Shahib, R. Daniel, C. Dhami, A.M. Laranjeira, T. Chambers, S. Phillips, R. Tewolde, A. Underwood, V.J. Chalker
Journal: Clinical Microbiology and Infection (2018)