tbuckley/cabot-search huggingface dataset:
Fatigue and weakness hinder patient social reintegration after liver transplantation
Authors: So Hyun Kang, YoungRok Choi, Ho-Seong Han, Yoo-Seok Yoon, Jai Young Cho, Sungho Kim, Kil Hwan Kim, In Gun Hyun, Ahmed Shehta
Journal: Clinical and Molecular Hepatology (2018)

With improvements in the survival of liver transplantation (LT) recipients, the focus is shifting to patient quality of life (QOL), and employment is an important factor in aiding the social reintegration of LT patients. This study aims to evaluate the current employment status of liver graft recipients and various factors that may hinder reemployment.Fifty patients above age 18 who underwent either living or deceased donor LT at a single center from March 2009 to July 2016 were interviewed during their visit to the outpatient clinic. The internally developed questionnaire consisted of 10 items. The Karnofsky Performance Scale and EQ-5D were used to evaluate patient function and QOL.A total of 25 (50%) patients returned to work after transplantation (the working group), and 21 (84%) patients in the working group returned to work within the first year after transplantation. In the non-working group (n=25), 17 (68%) answered that their health was the reason for unemployment. Fatigue and weakness were the most frequent symptoms.The data shows that as many as 50% of total patients returned to work after receiving LT. Fatigue and weakness were the most common complaints of the unemployed group, and resolving the causes of these symptoms may help to increase the employment rate.
Next-generation sequencing–based posttransplant monitoring of acute myeloid leukemia identifies patients at high risk of relapse
Authors: TaeHyung Kim, Joon Ho Moon, Jae-Sook Ahn, Yeo-Kyeoung Kim, Seung-Shin Lee, Seo-Yeon Ahn, Sung-Hoon Jung, Deok-Hwan Yang, Je-Jung Lee, Seung Hyun Choi, Ja-yeon Lee, Marc S. Tyndel, Myung-Geun Shin, Yoo Jin Lee, Sang Kyun Sohn, Seong-Kyu Park, Zhaolei Zhang, Hyeoung-Joon Kim, Dennis Dong Hwan Kim
Journal: Blood (2018)
CDK1 Interacts with Sox2 and Promotes Tumor Initiation in Human Melanoma
Authors: Dinoop Ravindran Menon, Yuchun Luo, John J. Arcaroli, Sucai Liu, Lekha Nair KrishnanKutty, Douglas G. Osborne, Yang Li, Jenny Mae Samson, Stacey Bagby, Aik-Choon Tan, William A. Robinson, Wells A. Messersmith, Mayumi Fujita
Journal: Cancer Research (2018)

: Cancers are composed of heterogeneous subpopulations with various tumor-initiating capacities, yet key stem cell genes associated with enhanced tumor-initiating capacities and their regulatory mechanisms remain elusive. Here, we analyzed patient-derived xenografts from melanoma, colon, and pancreatic cancer tissues and identified enrichment of tumor-initiating cells in MHC class I-hi cells, where CDK1, a master regulator of the cell cycle, was upregulated. Overexpression of CDK1, but not its kinase-dead variant, in melanoma cells increased their spheroid forming ability, tumorigenic potential, and tumor-initiating capacity; inhibition of CDK1 with pharmacologic agents reduced these characteristics, which was unexplained by the role of CDK1 in regulating the cell cycle. Proteomic analysis revealed an interaction between CDK1 and the pluripotent stem cell transcription factor Sox2. Blockade or knockdown of CDK1 resulted in reduced phosphorylation, nuclear localization, and transcriptional activity of Sox2. Knockout of Sox2 in CDK1-overexpressing cells reduced CDK1-driven tumor-initiating capacity substantially. Furthermore, GSEA analysis of CDK1hi tumor cells identified a pathway signature common in all three cancer types, including E2F, G2M, MYC, and spermatogenesis, confirming a stem-like nature of CDK1hi tumor cells. These findings reveal a previously unrecognized role for CDK1 in regulating tumor-initiating capacity in melanoma and suggest a novel treatment strategy in cancer via interruption of CDK1 function and its protein-protein interactions. SIGNIFICANCE: These findings uncover CDK1 as a new regulator of Sox2 during tumor initiation and implicate the CDK1-Sox2 interaction as a potential therapeutic target in cancer.
MONITOR VII: Treatment strategies of low grade ovarian carcinomas – A German survey of the Charité – Berlin and Kliniken Essen Mitte with support of the study groups NOGGO and AGO
Authors: S. Alavi, P. Harter, R. Richter, M. Keller, G. Oskay-Özcelik, A. Mustea, B. Schmalfeldt, P. Wimberger, F. Trillsch, S. Mahner, M. Klar, U. Wagner, R. Chekerov, A. du Bois, J. Sehouli
Journal: Annals of Oncology (2018)
Zirconium-89 (89Zr)-labeled bispecific T-cell engager (BiTE®) AMG 211 PET imaging to determine AMG 211 biodistribution in patients with gastrointestinal (GI) adenocarcinomas
Authors: K.L. Moek, S.J.H. Waaijer, I.C. Kok, F.V. Suurs, A. Brouwers, C.W. Menke-van der Houven van Oordt, T.T. Wind, J.A. Gietema, C.P. Schroder, S.V.K. Mahesh, A. Jorritsma-Smit, M.N. Lub-De Hooge, R.S.N. Fehrmann, D.J. de Groot, E.G.E. de Vries
Journal: Annals of Oncology (2018)
Humoral immune response to linear EpCAM-peptides induced by the mimotope cancer vaccine IGN101: Assessment by two independent methods
Authors: Astrid Durauer, Hans Loibner, Manfred Schuster, Thomas Bauernhofer, Hellmut Samonigg, Alois Jungbauer
Journal: Cancer Research (2007)

1856  IGN101 is a cancer vaccine for active specific immunotherapy of epithelial cancers, presumably acting via the Epithelial Cell Adhesion Molecule (EpCAM). IGN101 consists of 0.5 mg alum-adsorbed murine anti-EpCAM Mab 17-1A as vaccine antigen to trigger an immune response by repeated s.c. injections. The concept is based on observations that the immune response following passive treatment with murine Mab 17-1A may have contributed to clinical effects. IGN101 has been tested in several clinical trials, has shown excellent tolerability and induced a strong antibody response even when given together with chemotherapy (ASCO 2003). As result of a double-blind placebo controlled Phase II study, hints for survival prolongation were observed in stage IV colorectal cancer patients (ASCO 2005). A double-blind placebo controlled trial in 760 patients with adjuvant NSCLC is ongoing.  There are indications that Mab 17-1A used as vaccine antigen in IGN101 may contain mimotopes of EpCAM. In order to get insight into the mode of action, serum IgG of Rhesus monkeys and cancer patients pre and post vaccinations with IGN101 and serum IgG of human donors were tested for reactivity against overlapping synthetic peptides encompassing the entire sequence of EpCAM. The peptides were prepared by spot-synthesis on cellular supports in high density. Isolated IgG from sera was labeled with biotin and peptide binding was detected by incubation with streptavidin-horseradish peroxidase via chemiluminescence.  Pre-serum IgG of monkeys and serum IgG of human donors showed reactivity with certain peptides, pre-serum IgG of cancer patients generally had a lower reactivity to EpCAM peptides. Importantly, immune serum IgG of monkeys and of cancer patients defined a distinct set of additional EpCAM-peptides. Using competition experiments, anti-EpCAM-peptide antibodies against the idiotype of Mab 17-1A as well as to framework regions were detected, indicating that the direct antibody response to IGN101 (Ab2) in part cross-reacts with EpCAM epitopes.  For confirmation of these results in an independent format, target peptides identified by spot-synthesis were represented on the surface of Saccharomyces cerevisiae EBY100 by the pYD1 yeast display vector system. Binding of biotinylated IgG from pre- and immune sera was detected with streptavidin-FITC and quantitated by FACS. The results of the analysis of pre-immune and immune sera using yeast peptide display confirmed the results obtained via spot-synthesis of peptides.  In summary, vaccination of cancer patients with IGN101 directly induces antibodies that bind to certain epitopes of EpCAM and may trigger clinical effects of this cancer vaccine. It is planned to analyze sera of patients of placebo controlled clinical trials to get insight into a possible correlation of the induced antibody response to certain EpCAM epitopes on survival prolongation.
The epithelial zinc transporter <scp>ZIP</scp> 10 epigenetically regulates human epidermal homeostasis by modulating histone acetyltransferase activity
Authors: B.‐H. Bin, S.‐H. Lee, J. Bhin, T. Irié, S. Kim, J. Seo, K. Mishima, T.R. Lee, D. Hwang, T. Fukada, E.‐G. Cho
Journal: British Journal of Dermatology (2018)

Background The skin is the first organ that manifests changes in response to zinc deficiency. However, the molecular mechanism underlying how zinc is involved in skin homeostasis, especially its epigenetic regulation, is largely unknown. Objectives In this study we demonstrate the importance of zinc levels and the zinc transporter ZIP10 in the epigenetic maintenance of human epidermal homeostasis. Methods Adult human skin, including skin appendages, were stained with anti-ZIP10 antibody. Histone acetyltransferase (HAT) activity was assessed after treating human keratinocytes with ZIP10 small interfering (si)RNAs or the zinc chelator TPEN. ZIP10- or HAT-regulated genes were analysed based on limma bioinformatics analysis for keratinocytes treated with ZIP10 siRNAs or a HAT inhibitor, or using a public database for transcription factors. A reconstituted human skin model was used to validate the role of ZIP10 in epidermal differentiation and the functional association between ZIP10 and HAT. Results ZIP10 is predominantly expressed in the interfollicular epidermis, epidermal appendages and hair follicles. ZIP10 depletion resulted in epidermal malformations in a reconstituted human skin model via downregulation of the activity of the epigenetic enzyme HAT. This decreased HAT activity, resulting from either ZIP10 depletion or treatment with the zinc chelator TPEN, was readily restored by zinc supplementation. Through bioinformatics analysis for gene sets regulated by knockdown of SLC39A10 (encoding ZIP10) and HAT inhibition, we demonstrated that ZIP10 and HATs were closely linked with the regulation of genes related to epidermal homeostasis, particularly filaggrin and metallothionein. Conclusions Our study suggests that ZIP10-mediated zinc distribution is crucial for epidermal homeostasis via HATs. Therefore, zinc-dependent epigenetic regulation could provide alternatives to maintaining healthy skin or alleviating disorders with skin barrier defects.
Image Gallery: An unusual presentation of pseudoxanthomatous mastocytosis
Authors: F. Vaira, C.F. Tomasini
Journal: British Journal of Dermatology (2018)

Funding sources: none. Conflicts of interest: none declared. Dear Editor, (a) A 41‐year‐old man presented with a 1‐year history of multiple widespread yellowish, ovoid papular eruptions. (b) Lesions were in different evolutionary stages. Palms, soles, face and mucosae were spared. Itching was almost absent. Erythema was elicited upon rubbing the lesions. Blood count, tryptase and routine investigations were normal. Diffuse cutaneous mastocytosis pseudoxanthomatous variant was diagnosed by skin biopsy [(c) histological and (d) immunohistochemical evaluation]. The disease was stabilized with the use of antihistamines. Diffuse cutaneous mastocytosis pseudoxanthomatous variant is an extremely rare form of cutaneous mastocytosis.1 Furthermore, onset in such an acute and disseminated way in an adult is uncommon.2 ...
Abstract 12776: Outcomes and Survival With Home Intravenous Inotrope Therapy in Contemporary Heart Failure Management
Authors: Taimoor Hashim, Kumar Sanam, Marina I Revilla Martinez, Charity J Morgan, Jose A Tallaj, Salpy V Pamboukian, Renzo Y Loyaga-Rendon, James F George, Deepak Acharya
Journal: Circulation (2014)

Introduction: Inotrope use in decompensated congestive heart failure (CHF) is associated with improved hemodynamics, but did not improve outcomes in previous trials, with 50% 6-month mortality. However, many of these studies predated modern CHF therapies, including aldosterone antagonists, implantable cardioverter-defibrillators (ICDs), and resynchronization. We evaluated contemporary survival and outcomes on long-term inotropes in advanced CHF. Methods: We collected baseline and post-inotrope data on 197 consecutive patients discharged from our hospital between January 2007 and March 2013 on intravenous inotropes. Clinical, hemodynamic, catheterization, and survival data were collected. T-tests and Chi-square tests were used to compare outcomes, and Kaplan-Meier curves to evaluate survival. Results: Among the 197 patients, 25.8% were women, 40% had ischemic etiology and mean age was 54.4 years (standard deviation [SD] 14.6 years). Patients started on inotropes had CHF refractory to standard management, with mean baseline NYHA 3.7, cardiac index (CI) 1.7 L/min/m2, pulmonary capillary wedge pressure (PCWP) 25.6 mmHg, and left ventricular ejection fraction 17%. Milrinone was used in 85% and dobutamine in 15% of patients. Sixty-eight patients died, 24 were weaned off inotropes, 23 were transplanted, 32 received a LVAD, and 50 remained on inotropes. Mean NYHA class decreased from 3.7 to 2.7 (p &lt;0.001), CI increased from 1.7 L/min/m2 to 2.2 L/min/m2 (p &lt;0.001), and PCWP decreased from 25.6 mmHg to 21.1 mmHg (p &lt;0.001) . During follow-up, fifty-six patients (28%) had an infection related to intravenous inotropes. Thirty-three patients (16.7%) had at least one ICD shock. For the entire cohort, median survival was 18.1 months (Interquartile range [IQR] 4.7-37.1 months) and mean survival was 19.2 months (SD 1.5 months). For patients who did not receive a LVAD or transplant, median survival time was 13.2 months (IQR 3.7-37.1 months) and mean survival was 17.7 months (SD 1.5 months). Conclusions: Survival on long term-inotropes in this study was improved compared to previous reports. Routine ICD use may mitigate some arrhythmic risks of inotropes. Inotropes may be used as a bridge to initiate standard CHF therapy and subsequently weaned in selected cases.
Role of BMP-9 in human liver disease
Authors: Miya John, Kyung-Jin Kim, Sarah Da Won Bae, Liang Qiao, Jacob George
Journal: Gut (2018)

We read with interest the article by Breitkopf-Heinlein et al ,1 investigating the role of bone morphogenetic protein (BMP)-9 in liver regeneration and fibrosis. In mice, the authors demonstrate that BMP-9, a member of the transforming growth factor-β family, is primarily produced by hepatic stellate cells (HSCs) and is a profibrogenic factor. Inhibition or knockout of BMP-9 reduced liver fibrosis, while the recombinant protein increased the proliferation and migration of human HSCs. However, as shown in figure 1H and I of that study, rhBMP-9 did not upregulate fibrosis markers (eg, collagen I, fibronectin, platelet-derived growth factor B and α smooth muscle actin). While BMP-9 expression increased during the activation of primary human HSCs, the authors were unable to demonstrate a correlation between human hepatic BMP-9 expression and liver fibrosis stage from a publicly available microarray dataset.



Figure 1 
mRNA expression of BMP-9 pathway genes in human liver disease from microarray data. Boxplots showing BMP-9, BMP-10, Alk1 and ACVR2B mRNA in liver from normal and cirrhosis subjects (A), obese subjects with healthy liver and patients with NASH (B), and patients with mild …
Paediatric mastocytosis: a 12-year follow-up cohort
Authors: C. Meni, S. Georgin-Lavialle, L. Le Sachè de Peufeilhoux, J.P. Jais, S. Hadj-Rabia, J. Bruneau, S. Fraitag, K. Hanssens, P. Dubreuil, O. Hermine, C. Bodemer
Journal: British Journal of Dermatology (2018)

This study from Paris, France, followed 53 children with mastocytosis as they grew up. In mastocytosis there are increased numbers of mast cells (best known for their role in allergy) in the body, especially in the skin. In the childhood sub‐types, mast cell numbers are usually increased only in the skin and the condition is generally said to improve around puberty. Symptoms include itch, swelling and blistering in the skin but occasionally, if a lot of chemical messengers are released from huge numbers of mast cells, general (‘systemic’) symptoms such as flushing, abdominal pain, diarrhoea and headache occur. Most children improved, particularly if they had had mastocytosis for more than 12 years or had reached 16 years of age; in six the condition worsened, and in only three children did the mastocytosis clear completely from the skin. In 11 children the condition had started after two years of age and this was the only factor that predicted what would happen over time: the outcome was worse in this group. Systemic symptoms tended to improve, though they resolved completely in only five children and frequently persisted even if the skin changes improved. Three cases went on to develop more generalised mastocytosis, with involvement of bone in one case, bone and liver in the second case, and gut in the third. Forty‐six children showed a mutation in a gene called KIT, which is already known to be associated with mastocytosis, but there was no relationship between this, the type of mastocytosis, or whether or not the mastocytosis improved, persisted or worsened.
Nanobody-Facilitated Multiparametric PET/MRI Phenotyping of Atherosclerosis
Authors: Max L. Senders, Sophie Hernot, Giuseppe Carlucci, Jan C. van de Voort, Francois Fay, Claudia Calcagno, Jun Tang, Amr Alaarg, Yiming Zhao, Seigo Ishino, Anna Palmisano, Gilles Boeykens, Anu E. Meerwaldt, Brenda L. Sanchez-Gaytan, Samantha Baxter, Laura Zendman, Mark E. Lobatto, Nicolas A. Karakatsanis, Philip M. Robson, Alexis Broisat, Geert Raes, Jason S. Lewis, Sotirios Tsimikas, Thomas Reiner, Zahi A. Fayad, Nick Devoogdt, Willem J.M. Mulder, Carlos Pérez-Medina
Journal: JACC. Cardiovascular imaging (2018)

This study sought to develop an integrative positron emission tomography (PET) with magnetic resonance imaging (MRI) procedure for accurate atherosclerotic plaque phenotyping, facilitated by clinically approved and nanobody radiotracers. Noninvasive characterization of atherosclerosis remains a challenge in clinical practice. The limitations of current diagnostic methods demonstrate that, in addition to atherosclerotic plaque morphology and composition, disease activity needs to be evaluated. We screened 3 nanobody radiotracers targeted to different biomarkers of atherosclerosis progression, namely vascular cell adhesion molecule (VCAM)-1, lectin-like oxidized low-density lipoprotein receptor (LOX)-1, and macrophage mannose receptor (MMR). The nanobodies, initially radiolabeled with copper-64 (64Cu), were extensively evaluated in Apoe–/– mice and atherosclerotic rabbits using a combination of in vivo PET/MRI readouts and ex vivo radioactivity counting, autoradiography, and histological analyses. The 3 nanobody radiotracers accumulated in atherosclerotic plaques and displayed short circulation times due to fast renal clearance. The MMR nanobody was selected for labeling with gallium-68 (68Ga), a short-lived radioisotope with high clinical relevance, and used in an ensuing atherosclerosis progression PET/MRI study. Macrophage burden was longitudinally studied by 68Ga-MMR–PET, plaque burden by T2-weighted MRI, and neovascularization by dynamic contrast-enhanced (DCE) MRI. Additionally, inflammation and microcalcifications were evaluated by fluorine-18 (18F)-labeled fluorodeoxyglucose (18F-FDG) and 18F-sodium fluoride (18F-NaF) PET, respectively. We observed an increase in all the aforementioned measures as disease progressed, and the imaging signatures correlated with histopathological features. We have evaluated nanobody-based radiotracers in rabbits and developed an integrative PET/MRI protocol that allows noninvasive assessment of different processes relevant to atherosclerosis progression. This approach allows the multiparametric study of atherosclerosis and can aid in early stage anti-atherosclerosis drug trials.
Analysis of the clinical antibacterial and antituberculosis pipeline
Authors: Ursula Theuretzbacher, Simon Gottwalt, Peter Beyer, Mark Butler, Lloyd Czaplewski, Christian Lienhardt, Lorenzo Moja, Mical Paul, Sarah Paulin, John H Rex, Lynn L Silver, Melvin Spigelman, Guy E Thwaites, Jean-Pierre Paccaud, Stephan Harbarth
Journal: The Lancet Infectious Diseases (2018)
GW29-e1919 Early diagnosis of ruptured superior mesenteric artery secondary to chronic pancreatitis presenting as recurrent upper gastrointestinal hemorrhage:a case report and review of the literatures
Authors: Zi Ye, Yingxiong Huang, Peng Jiang, Jieyu Luo, Guangqi Chang, Hong Zhan
Journal: Journal of the American College of Cardiology (2018)
Prenatal Diagnosis of Hemoglobinopathies
Authors: Blanche P. Alter, C. Bernadette Modell, Denys Fairweather, John C. Hobbins, Maurice J. Mahoney, Fredric D. Frigoletto, Anita S. Sherman, David G. Nathan
Journal: New England Journal of Medicine (1976)

We attempted prenatal diagnosis of hemoglobinopathies in 15 cases--11 for beta-thalassemia and four for sickle-cell disease. Fetoscopy was used in seven cases, and placental aspiration in eight. One premature labor, with fetal loss, followed placental aspiration. Globin synthesis was assessed by incubation of samples with 3H-leucine and chain separation on carboxymethylcellulose columns. Homozygous disease was predicted in two pregnancies, which were interrupted, and the diagnosis confirmed. In one case homozygosity was suspected. A repeat test was advised but not accepted. The fetus had thalassemia trait. One pregnancy was interrupted despite our prediction of thalassemia trait. Eight pregnancies went to term. Seven predictions that the infants would not have homozygous disease were confirmed. One prediction of sickle trait proved to be sickle-cell disease. Although prenatal diagnosis of hemoglobinopathies is feasible, the present frequency of fetal loss and diagnostic error indicates need for improvement.
Abstract 14293: Time to Wound Healing and Major Adverse Limb Events in Patients With Critical Limb Ischemia Treated With Endovascular Therapy
Authors: Grant W Reed, Negar Salehi, Pejman Raeisi-Giglou, Umair Malik, Rami Kafa, Michael Maier, Mehdi H Shishehbor
Journal: Circulation (2015)

Introduction: There have been few studies evaluating the influence of time to wound healing on outcomes in patients with critical limb ischemia (CLI) after endovascular therapy. Methods: In this prospective study, patients with CLI treated with endovascular therapy were assessed for comorbidities, presence of wounds, wound healing, and major adverse limb events (MALE; major amputation, surgical endartectomy, or bypass) over time. The incidence of MALE was compared across patient and wound characteristics by Kaplan-Meier analysis. Associations between these variables and MALE were determined by Cox proportional hazards analysis. Results: A total of 252 consecutive patients with CLI were treated between November 1, 2011 and April 1, 2015; 179 (71%) had wounds, of which 97 (54%) healed. During median follow-up of 12.7 months (interquartile range 3.9 - 23.9 months), 46 (18%) had MALE. Wounds were associated with a greater risk of MALE (Hazard Ratio [HR] 3.5; 95% Confidence Interval [CI] 1.4-8.9; p=0.008). As a time-dependent covariate, wound healing was associated with less MALE (HR 0.23; 95% CI 0.10-0.53; p&lt;0.001), and MALE was more frequent in patients with unhealed wounds (23% vs 11%; p&lt;0.0001) (Figure - A). There was significantly less MALE in patients whose wounds healed within 4 months (24% vs 10%; p=0.032) (Figure - B), and less major amputation in those with healed wounds within 3 months (16% vs 5%; p=0.033). After multivariate adjustment for age, presence of diabetes, renal function, wound size, and procedural failure, independent predictors of MALE were wound healing as a time-dependent covariate (HR 0.18; 95% CI 0.08 - 0.40; p&lt;0.0001), and creatinine ≥ 2 (HR 2.3; 95% CI 1.3-4.2; p=0.005). Conclusions: A shorter time to wound healing is associated with less MALE in patients with CLI after endovascular therapy. Efforts should be made to achieve wound healing as quickly as possible in this population, especially in those with renal dysfunction.