tbuckley/cabot-search huggingface dataset:
Discrete serum protein signatures discriminate between human retrovirus associated hematologic and neurologic disease
Authors: Lisa H. Cazares, Lining Qi, Michael D. Ward, Michie Hisada, Michael W. Trosset, Steven Jacobson, O. John Semmes
Journal: Cancer Research (2005)

4792  The Human T-cell Leukemia Virus type I (HTLV-I) is the causative agent for Adult T-cell Leukemia (ATL) and HTLV-I-Associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP). Approximately 5% of infected individuals will develop either disease and currently there are no diagnostic tools for early detection or accurate assessment of disease state. We have employed high throughput expression profiling of serum proteins using mass spectrometry to identify protein expression patterns that can discern between disease states of HTLV-I-infected individuals. We previously analyzed serum from 42 ATL, 50 HAM/TSP, and 38 normal controls. Spectral data was processed with baseline subtraction and normalization followed by Classification and Regression Tree analysis to build a decision algorithm. A serial two-way decision algorithm was constructed using ATL vs. non-ATL for construction of the first tree and HAM vs. Normal for the second tree. This classification achieved a 77% correct classification rate across the three groups. In order to confirm this result we conducted a second study using a separate cohort of 69 ATL, 33 HAM/TSP, 117 asymptomatic HTLV-I carriers (AS) and 79 controls. We subjected the data from the second cohort to a separate analysis with CART. Our preliminary results from this second study resulted in 86% of ATL and 93.6% of all non-ATL being correctly classified. Among the non-ATL group a correct classification rate of 83.3% and 82.5% was achieved between HAM vs. Normal and HAM vs. AS respectively. From this second cohort we also used 10 ATL, 10 HAM and 10 control samples as a blind validation test set for the previous decision algorithm and achieved an overall correct classification rate of 73%. We will present the results of the completed cross-study analysis for assessment of biomarker robustness. Two major discriminatory peaks corresponding to 11,768 m/z and 11, 950 m/z were consistently utilized in the decision trees from each cohort. We employed affinity and sizing chromatography coupled with tandem mass spectrometry to identify three peaks specifically over-expressed in ATL; an 11.7 kD fragment of alpha trypsin inhibitor, and two contiguous fragments (19.9 kD and 11.9 kD) of haptoglobin-2. These results confirm that a decision structure utilizing cut-off values for expression of reproducible “peaks”, some of which have been sequence identified, can be a robust classifier for HTLV-1-disease.
A tryptophan metabolite of the skin microbiota attenuates inflammation in patients with atopic dermatitis through the aryl hydrocarbon receptor
Authors: Jinlei Yu, Yang Luo, Zhenlai Zhu, Yufeng Zhou, Licheng Sun, Jixin Gao, Jinlv Sun, Gang Wang, Xu Yao, Wei Li
Journal: Journal of Allergy and Clinical Immunology (2018)
Microdochectomy for pathologic nipple discharge.
Authors: Sanjay Zumberlal Baldota, Lee Min Lai, S P Raymond, Simon David Thomson
Journal: Journal of Clinical Oncology (2013)

e12032 Background: Nipple discharge has a known association with breast cancer, determing which cases to identify as being at high risk is a complex task for the clinician. The current policy at West Herfordshire hospital NHS Trust is to offer microdochectomy to all women who present with unilateral single duct nipple discharge, dominant duct discharge, or peristent duct discharge. The aim of this study was to determine if on basis of the pattern ofnipple discharge, patients could be subselected for microdochectomies, and to create a base line to allow future subselection of patients for survillience only. Methods: All patient with single duct unilateral spontaenous nipple discharge, who underwent microdochectomy, were assessed. Demongraphics, clincial presentation, radilogical assessment, cytology, core biopsy. This group of patients was anlysed and correlated with their final histological assessment. Results: 122 patients were analysed in this study. 7 ( 5.74%) were diagnosed with carcinomas. 4patients had ductal carcinoma in situ, three patients had dutcal carcinoma in situ and invasive ductal carcinoma, of these two patients had blood stained nipple discharge. two other patients had papillary carcinomas, one patient of these two had blood stained nipple discharge. 47 out of 122 patient presened with history of blood statined discharge,30 were negative for cytology, two patients had (ductal carcinoma in situ with Invasive ductal carcinoma and papillary ca) at final histololgy. 17 of the 47 showed cellular cytology.and one patient had intermediate grade DCIS confirmed on final histology, whereas in the remaining sixteen patients histological feaatures of papillomas, duct ectasia, and benign breast disease was noted. Of the 122 patient 42 patients had mammary duct ectasia (34%), 52 patients had papillomas (42%) at final hisotology. Conclusions: The negative predictive value (2/30), appears in this series appreas to be more valuable than, the positive predictive value (1/17) in cellular smears to predict ductal carcinoma or invasive ductal carcinoma. Cytological assessment of nipple discharge is equivocal at its best. Microdochectomy perford for nipple discharge results in a low rate of malignacy on excision and is comparable with other series.
Simultaneous Loss of Both Atypical Protein Kinase C Genes in the Intestinal Epithelium Drives Serrated Intestinal Cancer by Impairing Immunosurveillance
Authors: Yuki Nakanishi, Angeles Duran, Antoine L’Hermitte, Phillip M. Shelton, Naoko Nakanishi, Miguel Reina-Campos, Jianfeng Huang, Ferran Soldevila, Bas J.G. Baaten, Daniele V.F. Tauriello, Elias A. Castilla, Munveer S. Bhangoo, Fei Bao, Darren Sigal, Maria T. Diaz-Meco, Jorge Moscat
Journal: Immunity (2018)
Recurrence of Hereditary Hemorrhagic Telangiectasia After Liver Transplantation: Clinical Implications and Physiopathological Insights
Authors: Jérôme Dumortier, Sophie Dupuis‐Girod, Pierre‐Jean Valette, Alexander Valent, Olivier Guillaud, Jean‐Christophe Saurin, Valérie Hervieu, Philip Robinson, Henri Plauchu, Pierre Paliard, Olivier Boillot, Jean‐Yves Scoazec
Journal: Hepatology (2018)

Liver transplantation (LT) has been proposed as a curative treatment in hereditary hemorrhagic telangiectasia (HHT) with severe hepatic involvement. We provide a long-term evaluation of graft status after LT for HHT, with a focus on the risk of recurrence. The present study included all patients prospectively followed up after LT for HHT in the Lyon Liver Transplant Unit from 1993 to 2010, with a survival of more than 1 year. Protocol clinical, radiological, and histological examinations were performed at regular intervals. Fourteen patients were included (13 women and one man). Median age at LT was 52.5 years (range: 33.1-66.7). In eight patients (seven female), disease recurrence was diagnosed by abnormal radiological features, suggestive of microcirculatory disturbances. Typical vascular lesions, including telangiectasia, were demonstrated by liver biopsy in five of these patients. The median interval between LT and diagnosis of recurrence was 127 months (range: 74-184). The risk of recurrence increased over time; estimated cumulative risk was 47.9% at 15 years. Liver tissue analysis found the coexistence of an angiogenic process combined with endothelial microchimerism, as shown by the presence of vascular lining cells of recipient origin. Conclusion: The present data show that disease recurrence occurs, usually after a long delay, in a significant number of patients treated by LT for liver complications of HHT. This strongly supports the necessity of a lifelong follow-up and suggests that therapeutic strategy needs discussion and evaluation, especially of the role of potential adjuvant treatments to LT, such as antiangiogenic medications, when recurrent disease appears.
Mutations in Chromatin Modifier and Ephrin Signaling Genes in Vein of Galen Malformation
Authors: Daniel Duran, Xue Zeng, Sheng Chih Jin, Jungmin Choi, Carol Nelson-Williams, Bogdan Yatsula, Jonathan Gaillard, Charuta Gavankar Furey, Qiongshi Lu, Andrew T. Timberlake, Weilai Dong, Michelle A. Sorscher, Erin Loring, Jennifer Klein, August Allocco, Ava Hunt, Sierra Conine, Jason K. Karimy, Mark W. Youngblood, Jinwei Zhang, Michael L. DiLuna, Charles C. Matouk, Shrikant Mane, Irina R. Tikhonova, Christopher Castaldi, Francesc López-Giráldez, James Knight, Shozeb Haider, Mariya Soban, Seth L. Alper, Masaki Komiyama, Andrew F. Ducruet, Joseph M. Zabramski, Alan Dardik, Brian P. Walcott, Christopher J. Stapleton, Beverly Aagaard-Kienitz, Georges Rodesch, Eric Jackson, Edward R. Smith, Darren B. Orbach, Alejandro Berenstein, Kaya Bilguvar, Miikka Vikkula, Murat Gunel, Richard P. Lifton, Kristopher T. Kahle
Journal: Neuron (2018)
Association of Screening and Treatment for Preoperative Asymptomatic Bacteriuria With Postoperative Outcomes Among US Veterans
Authors: Jaime Gallegos Salazar, William O’Brien, Judith M. Strymish, Kamal Itani, Westyn Branch-Elliman, Kalpana Gupta
Journal: JAMA Surgery (2018)

Limited data suggest that screening for asymptomatic bacteriuria (ASB) prior to nonurologic procedures is not useful. However, high-quality evidence to support consensus recommendations and influence clinical practice is lacking.To characterize the association between detection and treatment of preoperative ASB and postoperative outcomes.This retrospective cohort study involved patients, predominantly male veterans, who underwent surgical procedures in 109 US facilities within the US Department of Veterans Affairs health care system from October 1, 2008, to September 30, 2013. Participants included patients (n = 68 265) who had cardiac, orthopedic, or vascular surgical procedures. Each received a planned clinician review of complete medical records for antimicrobial prophylaxis as well as 30-day surgical-site infection (SSI) and urinary tract infection (UTI) outcomes, and each had a preoperative urine culture result available within the 30 days prior to the procedure. Data analysis was performed from December 2016 to August 2018.The primary outcome was the association between preoperative ASB and postoperative SSI. The secondary outcomes included postoperative UTI and the association between antimicrobial therapy for ASB and postoperative infectious outcomes.In total, 68 265 patients (65 664 [96.2%] were men and 2601 [3.8%] were women, with a mean [SD] age of 64.6 [9.2] years) were identified, and 17 611 (25.8%) were eligible for inclusion in the primary analysis. Preoperative urine cultures were performed in 17 749 (26.0%) patients, and the results were positive in 755 (4.3%), of which 617 (81.7%) were classified as ASB. With adjustments for age, American Society of Anesthesiologists class, smoking status, race/ethnicity, sex, and diabetes status, patients with or without ASB had similar odds of SSI (2.4% vs 1.6%; adjusted odds ratio [aOR], 1.58; 95% CI, 0.93-2.70; P = .08). Receipt of antimicrobial therapy with activity against the ASB organism was not associated with a reduced SSI risk (aOR, 1.01; 95% CI, 0.28-3.65; P = .99). Urinary tract infection occurred in 14 (3.3%) of 423 patients with ASB and 196 (1.5%) of 12 913 patients without ASB (aOR, 1.42; 95% CI, 0.80-2.49; P = .22). Treatment or prophylaxis for the ASB organism similarly was not associated with reduced odds of postoperative UTI (aOR 0.68; 95% CI, 0.20-2.30; P = .54). The ASB organisms matched a postoperative wound culture in 2 cases, both Staphylococcus aureus.The findings of this study suggest that receipt of antimicrobial therapy with activity against ASB organisms identified in preoperative urine cultures was not associated with reductions in the risk for postoperative infections, including UTI and SSI; such findings suggest there is evidence for discontinuing the practice of screening and treatment for preoperative ASB.
Controversies in drug allergy: Testing for delayed reactions
Authors: Elizabeth J. Phillips, Paul Bigliardi, Andreas J. Bircher, Ana Broyles, Yoon-Seok Chang, Wen-Hung Chung, Rannakoe Lehloenya, Maja Mockenhaupt, Jonny Peter, Munir Pirmohamed, Jean-Claude Roujeau, Neil H. Shear, Luciana Kase Tanno, Jason Trubiano, Rocco Valluzzi, Annick Barbaud
Journal: Journal of Allergy and Clinical Immunology (2018)
The impact of HIPEC on the anticancer immune response
Authors: L. Roth, E. Breuer, A. Gupta, R. Graf, P.-A. Clavien, K. Lehmann
Journal: Annals of Oncology (2018)

Background: The outcome of peritoneal carcinomatosis, often occurring due to appendix or colorectal cancer, has dramatically improved with the combination of cytoreductive surgery (CRS) and hyperthermic (43 °C) intraperitoneal chemotherapy (HIPEC). Nevertheless, recurrence of the disease presumably due to remnant cancer cells limits survival of the patients suggesting further optimization in HIPEC treatment. Therefore, it is important to understand mechanisms operating behind HIPEC treatment. Since chemotherapy may induce immunogenic changes, we analyzed effects of MitomycinC/Doxorubicin (M/D), widely used chemotherapeutics in HIPEC settings, on the immunogenicity of colorectal cancer cells in-vitro. Methods: Colorectal cell-lines were treated with M/D for 30 minutes with and without hyperthermia (430C). After the treatment, cells were further incubated at 370C for 72 hours. The expression of immunogenic cancer-testig antigens (CTA) was analyzed using qRT-PCR and western blot. To assess DC maturation, we set up a co-culture between differentially treated colorectal cells and monocyte-derived DC`s. We analyzed surface markers such as HLA-DR, CD 86 and CD 83 to assess DC maturation using flow cytometry. Further, the activation of cytotoxic T-cells was measured by intracellular IFN-y staining after co-culture with DC`s that were pre-incubated with treated and untreated colorectal cancer cells. Results: Initial qRT-PCR screening of CTA revealed that two namely, Cyclin A1 and SSX-4 were upregulated after HIPEC treatment. Compared to the control condition (no drug, 370C), M/D in HIPEC condition led to an increase of Cyclin A1 up to 53 folds and SSX-4 to 30 folds. The amount of Cyclin A1 protein was doubled compared to the control treatment (p = 0.0015, CI mean volume intensity 0.1989 – 0.4233). After co-culturing with HIPEC treated colorectal cancer cells, we noticed significant expression in CD 83, a DC activation marker. DCs that were activated upon incubation with HIPEC-treated cancer cells were able to prime cytotoxic T-cells leading to enhance IFN-y production. Conclusions: HIPEC treatment can cause immunogenic changes in colorectal cancer cells. This could explain a part of the mechanism, how HIPEC treatment may work and inclusion of an immunotherapy may improve outcome of this treatment. Legal entity responsible for the study: Kuno Lehmann. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.
Abstract MP21: Feasibility of Electronic Health Records-based community surveillance of cardiovascular disease: Findings from the Atherosclerosis Risk in Communities Study.
Authors: Brittany M Bogle, Wayne D Rosamond, Aaron R Folsom, Paul Sorlie, Elsayed Z Soliman, Lynne Wagenknecht, Anna Kucharska-Newton, Carlton Moore, Stephanie W Haas, Gerardo Heiss
Journal: Circulation (2018)

Background: Accurate community surveillance of cardiovascular disease requires hospital record abstraction, which is typically a manual process. The costly and time-intensive nature of manual abstraction precludes its use on a regional or national scale in the US. Whether an efficient system can accurately reproduce traditional community surveillance methods by processing electronic health records (EHRs) has not been established. Objective: We sought to develop and test an EHR-based system to reproduce abstraction and classification procedures for acute myocardial infarction (MI) as defined by the Atherosclerosis Risk in Communities (ARIC) Study. Methods: Records from hospitalizations in 2014 within ARIC community surveillance areas were sampled using a broad set of ICD discharge codes likely to harbor MI. These records were manually abstracted by ARIC study personnel and used to classify MI according to ARIC protocols. We requested EHRs in a unified data structure for the same hospitalizations at 6 hospitals and built programs to convert free text and structured data into the ARIC criteria elements necessary for MI classification. Per ARIC protocol, MI was classified based on cardiac biomarkers, cardiac pain, and Minnesota-coded electrocardiogram abnormalities. We compared MI classified from manually abstracted data to (1) EHR-based classification and (2) final ICD-9 coded discharge diagnoses (410-414). Results: These preliminary results are based on hospitalizations from 1 hospital. Of 684 hospitalizations, 355 qualified for full manual abstraction; 83 (23%) of these were classified as definite MI and 78 (22%) as probable MI. Our EHR-based abstraction is sensitive (&gt;75%) and highly specific (&gt;83%) in classifying ARIC-defined definite MI and definite or probable MI (Table). Conclusions: Our results support the potential of a process to extract comprehensive sets of data elements from EHR from different hospitals, with completeness and accuracy sufficient for a standardized definition of hospitalized MI.
Nanoencapsulation introduces long-acting phenomenon to tenofovir alafenamide and emtricitabine drug combination: A comparative pre-exposure prophylaxis efficacy study against HIV-1 vaginal transmission
Authors: Subhra Mandal, Guobin Kang, Pavan Kumar Prathipati, You Zhou, Wenjin Fan, Qingsheng Li, Christopher J. Destache
Journal: Journal of Controlled Release (2018)
Improving psychosocial services for vulnerable families with young children: strengthening links between health and social services in Germany
Authors: Ilona Renner, Victoria Saint, Anna Neumann, Daria Ukhova, Sabine Horstmann, Ullrich Boettinger, Martina Dreibus, Astrid Kerl-Wienecke, Pilar Wulff, Paul Mechthild, Heidrun Thaiss
Journal: BMJ (2018)

Ilona Renner and colleagues describe cross-sectoral collaborative efforts in Germany to enhance the skills of parents to care for young children
Non-invasive biomarkers derived from the extracellular matrix associate with response to immune checkpoint blockade (anti-CTLA-4) in metastatic melanoma patients
Authors: Christina Jensen, Daniel Hargbøl Madsen, Morten Hansen, Henrik Schmidt, Inge Marie Svane, Morten Asser Karsdal, Nicholas Willumsen
Journal: Journal for ImmunoTherapy of Cancer (2018)

<h3>Background</h3> Excessive extracellular matrix (ECM) remodeling and a reactive stroma can affect T-cell infiltration and T-cell activity in the tumor and hereby influence response to immune checkpoint inhibitors (ICI). In the pursuit of finding biomarkers that predict treatment response, we evaluated the association between serum biomarkers of collagen and vimentin turnover and outcomes in metastatic melanoma patients treated with the anti-CTLA-4 antibody ipilimumab (IPI). <h3>Methods</h3> Type III collagen formation (PRO-C3), MMP-degraded type I, type III and type IV collagens (C1M, C3M and C4M), and citrullinated and MMP-degraded vimentin (VICM) were measured with ELISAs in serum from metastatic melanoma patients before (<i>n</i>&nbsp;= 66) and 3 weeks after (<i>n</i>&nbsp;= 52) initiation of IPI treatment. Biomarker levels were associated with Disease Control Rate (DCR) and survival outcomes. <h3>Results</h3> We found that baseline levels of PRO-C3 (<i>p</i>&nbsp;= 0.011), C1M (<i>p</i>&nbsp;= 0.003), C3M (<i>p</i>&nbsp;= 0.013) and C4M (<i>p</i>&nbsp;= 0.027) were significantly elevated in patients with progressive disease (PD). Univariate Cox regression analysis identified high PRO-C3 (<i>p</i>&nbsp;= 0.021) and C4M (<i>p</i>&nbsp;= 0.008) as predictors of poor overall survival (OS) and the biomarkers remained significant when evaluated with other covariates (PRO-C3 (<i>p</i>&nbsp;= 0.049) and C4M (<i>p</i>&nbsp;= 0.046)). Multivariate analysis identified VICM as a predictor of longer OS (<i>p</i>&nbsp;= 0.026). Similarly, a high C3M/PRO-C3 ratio predicted for increased OS (<i>p</i>&nbsp;= 0.034). Only C3M (<i>p</i>&nbsp;= 0.003) and VICM (<i>p</i>&nbsp;&lt; 0.0001) increased 3 weeks after treatment. <h3>Conclusions</h3> ECM and tissue remodeling quantified in pre-treatment serum were associated with response and survival outcomes in metastatic melanoma patients treated with IPI. This highlights the importance of addressing the ECM and stromal component non-invasively in future ICI studies.
Regulatory mechanisms of deoxycytidine kinase in cancer cells: Promoter hypermethylation and micro-RNAs
Authors: Jasmina Hodzic, Auke Adema, Begonia Diosdado Calvo, Gertjan Kaspers, Godefridus Peters, Isabelle Hubeek
Journal: Cancer Research (2008)

2459  Deoxycytidine kinase (dCK) is the most important enzyme in the deoxyribonucleoside salvage pathway and phosphorylates a variety of deoxynucleoside analogs, such as gemcitabine and ara-C, which are frequently used as anticancer compounds. This activation to nucleotides is crucial for their activity since a dCK deficiency (dCK-) leads to resistance, while we earlier observed a highly significant relation between dCK activity and in vivo sensitivity of xenografts to gemcitabine. Therefore identification of dCK regulating mechanisms is of utmost importance. We hypothesized that epigenetic regulation could affect the function of dCK by DNA methylation of SP1 binding sites in the dCK promoter region, while posttranscriptional regulation of dCK might be mediated by micro-RNAs. To study this we used cell lines from different origins: leukemia (CEM, CEM-dCK-), NSCLC (A549, H460, SW1573), colon cancer (WiDr, HT-29, Colo320), ovarian cancer (A2780, AG6000) and the noncancerous HEK 293 cell line. In vitro sensitivity to gemcitabine was determined by SRB or MTT-assay. dCK activity was measured using chlorodeoxyadenosine as a substrate, and protein expression by Western blotting. The gemcitabine-resistant cell lines AG6000 and CEM-dCK- lacked dCK protein. The highest dCK protein expression was detected in CEM, A2780 and Colo320 cells, and the lowest dCK in A549 and HEK cells. A negative correlation was observed between dCK expression and in vitro sensitivity to gemcitabine (R=-0.74, R=0.04) in the solid tumor cell lines. To study hypermethylation of the dCK promoter region several methylation specific PCRs (MSP) were setup which identified methylation of one SP1 binding site in the dCK promoter in HEK, SW1573, Colo320, H460, and CEM cells. There was no clear correlation between methylation status and dCK protein expression. TargetScan and MiRANDA prediction algorithms revealed several possible dCK targeting miRNAs and identified hsa-mir-330 as the best hit. Expression of hsa-mir-330 as measured by Taqman analysis, revealed a large variation among cell lines and correlated with in vitro gemcitabine sensitivity (IC50s) in colorectal and lung cancer cells (R = 0.79, p= 0.03). Exposure to gemcitabine also appeared to influence mir-hsa-330 levels in these cell lines. Furthermore, hsa-mir-330 expression correlated with dCK activity (R=0.74, p=0.04) in our cell line panel, but not with dCK protein expression, suggestion a role of miRNA in regulation of dCK activity. In human xenografts (A2780, Calu, WiDR and Panc-02) hsa-mir-330 expression also correlated with dCK activity (R=1, p=0.00). In conclusion, both promoter methylation and hsa-mir-330 miRNA appear to regulate dCK expression and activity in cancer cells. Both mechanisms appear to contribute to sensitivity to deoxynucleoside analogs like gemcitabine in cancer cell lines.