tbuckley/cabot-search huggingface dataset:
Rapid Clearance Profile of Plasma Circulating Tumor HPV Type 16 DNA during Chemoradiotherapy Correlates with Disease Control in HPV-Associated Oropharyngeal Cancer
Authors: Bhishamjit S. Chera, Sunil Kumar, Brian T. Beaty, David Marron, Stuart Jefferys, Rebecca Green, Emily C. Goldman, Robert Amdur, Nathan Sheets, Roi Dagan, D. Neil Hayes, Jared Weiss, Juneko E. Grilley-Olson, Adam Zanation, Trevor Hackman, Jeffrey M. Blumberg, Samip Patel, Mark Weissler, Xianming M. Tan, Joel S. Parker, William Mendenhall, Gaorav P. Gupta
Journal: Clinical Cancer Research (2019)

To identify a profile of circulating tumor human papilloma virus (HPV) DNA (ctHPVDNA) clearance kinetics that is associated with disease control after chemoradiotherapy (CRT) for HPV-associated oropharyngeal squamous cell carcinoma (OPSCC).A multi-institutional prospective biomarker trial was conducted in 103 patients with (i) p16-positive OPSCC, (ii) M0 disease, and (iii) receipt of definitive CRT. Blood specimens were collected at baseline, weekly during CRT, and at follow-up visits. Optimized multianalyte digital PCR assays were used to quantify ctHPVDNA (types 16/18/31/33/35) in plasma. A control cohort of 55 healthy volunteers and 60 patients with non-HPV-associated malignancy was also analyzed.Baseline plasma ctHPVDNA had high specificity (97%) and high sensitivity (89%) for detecting newly diagnosed HPV-associated OPSCC. Pretreatment ctHPV16DNA copy number correlated with disease burden, tumor HPV copy number, and HPV integration status. We define a ctHPV16DNA favorable clearance profile as having high baseline copy number (>200 copies/mL) and >95% clearance of ctHPV16DNA by day 28 of CRT. Nineteen of 67 evaluable patients had a ctHPV16DNA favorable clearance profile, and none had persistent or recurrent regional disease after CRT. In contrast, patients with adverse clinical risk factors (T4 or >10 pack years) and an unfavorable ctHPV16DNA clearance profile had a 35% actuarial rate of persistent or recurrent regional disease after CRT (P = 0.0049).A rapid clearance profile of ctHPVDNA may predict likelihood of disease control in patients with HPV-associated OPSCC patients treated with definitive CRT and may be useful in selecting patients for deintensified therapy.
Abstract 20088: Impact of Patent Foramen Ovale and Intracardiac Devices on Traditional Risk Factors for Stroke: When Low Risk Means High Risk?
Authors: Manijeh Assar, Michael Sultan, Sumit Agarwal, Martha Gulati, Supriya Bhardwaj, Salem Al Rabadi, Adnan Habib, Erica Flores, Srilekha Sridhara, George Gellert, Orazio Amabile, Mark Tasset, Vidette Villareal-Argente, Claire Kelley, Sharon Kusne, Zuhdi Jasser, Michael Morris, Timothy Byrne, Kenith Fang, Wilbur Su, Ashish Pershad, Divya Ratan Verma
Journal: Circulation (2017)

Hypothesis: To define the risk of stroke in patients with PFO and intracardiac devices with or without traditional risk factors Background: Risk of stroke in patients with known patent foramen oval...
Endoscopic transcecal appendectomy
Authors: Xiang-lei Yuan, Onpan Cheung, Jiang Du, Lian-song Ye, Bing Hu
Journal: Endoscopy (2019)

A 53-year-old woman was referred to our hospital after a 1-cm submucosal bulge near the appendiceal orifice ([Fig. 1]) was incidentally found during a colonoscopy. The patient was asymptomatic. Her past medical history was significant only for acute appendicitis 20 years previously; she had suffered no complications, and had recovered fully with only conservative management. Endoscopic ultrasonography showed a hypoechoic lesion with an homogeneous echo, originating from the muscularis propria ([Fig. 2]).
ENDOSCOPIC CLOSURE OF COMPLEX OESOPHAGO-PLEURO-CUTANEOUS FISTULA
Authors: C Puli, V Maddirala, A Singh, P Shasi, D Khoo
Journal: Endoscopy (2019)

Oesophago-pleural fistula is a difficult complication to treat in post gastrectomy patients, often requiring surgical interventions. However, recent advances mean that endoscopic techniques can provide a safe and effective alternative. Here, we describe a case of successful endoscopic closure of a oesophago-jejunal-pleurocutaneous fistula using multimodality endoscopic closure.
ANTERIOR VERSUS POSTERIOR MYOTOMY DURING POEM FOR THE TREATMENT OF ACHALASIA: SYSTEMATIC REVIEW AND META-ANALYSIS OF RANDOMIZED CLINICAL TRIALS
Authors: E Rodríguez de Santiago, N Mohammed, A Manolakis, Y Shimamura, M Onimaru, H Inoue
Journal: Endoscopy (2019)

The optimal orientation of the myotomy during peroral endoscopic myotomy (POEM) is unknown. This meta-analysis aims to compare anterior and posterior myotomy regarding clinical success and safety.
Glutathione S-Transferase Regulates Mitochondrial Populations in Axons through Increased Glutathione Oxidation
Authors: Gaynor A. Smith, Tzu-Huai Lin, Amy E. Sheehan, Wynand Van der Goes van Naters, Lukas J. Neukomm, Hillary K. Graves, Dana M. Bis-Brewer, Stephan Züchner, Marc R. Freeman
Journal: Neuron (2019)
EFFECTIVENESS OF THE ALGORITHM OF DEPTH DIAGNOSIS FOR SUPERFICIAL BARRETT'S ADENOCARCINOMA
Authors: S Yoshinaga, I Oda, K Furutani, D Hihara, M Koga, T Ito, H Cho, M Yamada, S Abe, S Nonaka, H Suzuki, Y Saito, H Daiko, H Katai, H Taniguchi, S Sekine
Journal: Endoscopy (2019)

Although the depth of invasion is the important factor to make a decision in treatment, little is known about the correlation between endoscopic feature and invasion depth of superficial Barrett's adenocarcinoma (SBA). We aimed to investigate the endoscopic findings indicating deep submucosal invasion of SBA and develop the algorithm of depth diagnosis.
FIRST SUCCESSFUL SCAR EXCISION, RE-VASCULARIZATION AND TRANSPLATATION OF SMALL INTESTINAL MUCOSA TO THE CERVICAL ESOPHAGUS IN MAN
Authors: J Hochberger, M Loss, J Bernhardt, P Koehler, S Koop
Journal: Endoscopy (2019)

A 62 year old man had undergone a curative circumferential tubular endoscopic submucosal dissection (ESD) from 20 – 27 cm aborally in july 2015 due to an early SCC located in the upper esophageal sphincter area.
DON'T FORGET TO PERFORM BIOPSIES IN NORMAL ILEOCOLONOSCOPY FOR CHRONIC DIARRHEA
Authors: G Leoncini, F Bonfante, O Bonzanini, S Polo, G Aimo, V Villanacci
Journal: Endoscopy (2019)

The aim of the present study is to better assess the prevalence of colitis with unremarkable endoscopic features, through clinical-pathological correlations.
EFTR WITH OTSC IN COLORECTUM: WHAT HAPPENS WHEN THE LESION IS TRAPPED IN THE OVER-THE-SCOPE-CLIP AND IS NOT RESECTED
Authors: H Uchima, D Barquero, JM Esteban, JC Espinos, JC Marin, P Rosón, F Fernandez Cadenas, MA Palacio Galan, I Puig, J Rodriguez-Sanchez, M Fraile, A Ortega, J Arribas, L Mel, F Sabado, J García Lledó, A Fernandez, A Mata, E Albeniz
Journal: Endoscopy (2019)

Endoscopic full-thickness resection (EFTR) in the colorectum using the FTRD may be difficult sometimes due to poor traction or loosing of the resection plane, and part of the lesion or the whole of it might get trapped inside the over-the-scope clip (OTSC).
TCF21 and AP-1 interact through epigenetic modifications to regulate coronary artery disease gene expression
Authors: Quanyi Zhao, Robert Wirka, Trieu Nguyen, Manabu Nagao, Paul Cheng, Clint L. Miller, Juyong Brian Kim, Milos Pjanic, Thomas Quertermous
Journal: Genome Medicine (2019)

Genome-wide association studies have identified over 160 loci that are associated with coronary artery disease. As with other complex human diseases, risk in coronary disease loci is determined primarily by altered expression of the causal gene, due to variation in binding of transcription factors and chromatin-modifying proteins that directly regulate the transcriptional apparatus. We have previously identified a coronary disease network downstream of the disease-associated transcription factor TCF21, and in work reported here extends these studies to investigate the mechanisms by which it interacts with the AP-1 transcription complex to regulate local epigenetic effects in these downstream coronary disease loci. Genomic studies, including chromatin immunoprecipitation sequencing, RNA sequencing, and protein-protein interaction studies, were performed in human coronary artery smooth muscle cells. We show here that TCF21 and JUN regulate expression of two presumptive causal coronary disease genes, SMAD3 and CDKN2B-AS1, in part by interactions with histone deacetylases and acetyltransferases. Genome-wide TCF21 and JUN binding is jointly localized and particularly enriched in coronary disease loci where they broadly modulate H3K27Ac and chromatin state changes linked to disease-related processes in vascular cells. Heterozygosity at coronary disease causal variation, or genome editing of these variants, is associated with decreased binding of both JUN and TCF21 and loss of expression in cis, supporting a transcriptional mechanism for disease risk. These data show that the known chromatin remodeling and pioneer functions of AP-1 are a pervasive aspect of epigenetic control of transcription, and thus, the risk in coronary disease-associated loci, and that interaction of AP-1 with TCF21 to control epigenetic features, contributes to the genetic risk in loci where they co-localize.
The Role of Early-Phase Design—Response
Authors: Mark R. Conaway, Gina R. Petroni
Journal: Clinical Cancer Research (2019)

Dr. Ratain's letter allows us to reiterate the primary message of the publication: to meet the challenges of contemporary dose-finding, the 3+3 algorithm should be abandoned. This commonly used algorithm performed poorly even in the simple, single-agent, monotonic dose toxicity scenario presented in
Defining the physiological miRNA landscape in nipple aspirate fluid
Authors: S.I.S. Patuleia, C.B. Moelans, C.H. van Gils, P.J. van Diest, E. van der Wall
Journal: Annals of Oncology (2019)

Background: MicroRNAs (miRNAs) are small, non-protein-coding RNAs that can bind and suppress specific target messenger RNAs (mRNAs). Their dysregulation has been shown to affect the hallmarks of cancer and an increasing number of studies have identified miRNAs as potential biomarkers for cancer diagnosis. The ability to detect local oncogenic or tumor suppressor miRNAs in nipple aspirate fluid (NAF) could be of great value for early breast cancer diagnosis. To define the landscape of miRNAs physiologically present in the breast ducts, we analyzed their expression patterns in healthy NAF samples. Methods: A total of 41 NAF samples (8 ng total RNA) from healthy women were profiled using the TaqMan™ OpenArray™ Human Advanced MicroRNA Panel (ThermoFisher Scientific) targeting 754 human mature miRNAs. Non-parametric statistical analyses were performed using SPSS statistics®. Results: Out of the 754 interrogated miRNAs, 39% had measurable expression levels in NAF. In line with previous miRNA studies in breast milk, the majority of highly expressed miRNAs in NAF (36/top 50) have immune-related roles. Few of the top 50 miRNAs in NAF were significantly correlated with BMI (miR-223-3p) or parity (let-7b-5p, miR-92a-3p, miR-29b-3p and miR-30d-5p). No correlation was found between miRNA expression and age or having a first degree relative with breast cancer. Interestingly, NAF sample color significantly affected the expression level of 4/50 miRNAs. MiR-205-5p, miR-200b-3p, miR-26a-5p and miR-210-3p showed significantly lower expression levels in green or brown samples compared to bloody, orange or pink samples (p = 0.029, p = 0.022, p = 0.011, and p = 0.009, respectively). Conclusions: MiRNAs can reliably be detected in NAF of healthy subjects and most of them are immune-related. Our data reveals the first documented NAF-derived miRNA physiological expression pattern, with very few highly expressed miRNAs associated with established breast cancer risk factors. Of note, caution should be taken when interpreting miRNA expression levels in differently colored samples, as this proves to be a significant confounder. Currently, breast cancer NAF samples are being collected in the context of a Dutch trial and their analysis will soon reveal whether breast cancer specific miRNAs can be identified. Clinical trial identification: METC 14-497 (Dense-on) and METC 16-337 (Ornament). Legal entity responsible for the study: Department of Pathology, UMC Utrecht. Funding: Pink Ribbon, KWF. Disclosure: All authors have declared no conflicts of interest.
Ceftriaxone-resistant Salmonella enterica serotype Typhi in a pregnant traveller returning from Karachi, Pakistan to Denmark, 2019
Authors: Anne Line Engsbro, Hans Søe Riis Jespersen, Maria Ingeborg Goldschmidt, Sarah Mollerup, Peder Worning, Martin Schou Pedersen, Henrik Westh, Uffe Vest Schneider
Journal: Eurosurveillance (2019)

We describe a ceftriaxone-resistant Salmonella Typhi bacteraemia in a pregnant woman returning from a family visit in Pakistan. Whole genome sequencing confirmed similarity to a Pakistani outbreak clone. Pregnancy and unawareness of this outbreak delayed appropriate antibiotic therapy. Concurrently, we detected faecal carriage of a carbapenemase-producing Escherichia coli. Awareness of the ongoing outbreak should affect empiric treatment of typhoid fever and hygiene precautions in travellers returning from Pakistan. Meropenem may be warranted in severe cases.
Expression of ER, PR, HER2 and Ki67 in the neoadjuvant GeparX trial: Comparison of central immunohistochemistry with an automated cartridge-based system for mRNA assessment (on behalf of the GBG neoadjuvant and translational subboard)
Authors: C. Denkert, P. Jank, T. Link
Journal: Annals of Oncology (2019)

Background: Measurement of hormone receptors, HER2 and Ki-67 is prognostic for breast cancer (BC) outcome and prediction of therapy response. The Xpert® Breast Cancer STRAT4 based on RT-qPCR, is used to classify BC tissues regarding their hormone receptor status, HER2 and proliferation via Ki-67. This study compares the mRNA expression analysis of ER, PR, HER2, and Ki-67 in a large clinical trial cohort by an automated in-vitro diagnostic platform and central IHC. Methods: Breast cancer patients from the prospective GBG multicenter trial GeparX (NCT02682693) (still recruiting) were included in this biomarker project. We used formalin-fixed paraffin embedded (FFPE) pretherapeutical core biopsies with a tumor content >10%. A 4µm FFPE tissue section was first processed with the Xpert® FFPE Lysis Kit, the sample lysate was placed in the GeneXpert® cartridge system in which the purification, amplification and real-time detection of the gene expression of ER, PR, HER2 and Ki-67 took place automatically. Results: Of 503 samples with valid mRNA measurements, 258 samples (51,3%) were ER-positive, 196 (39%) PR-positive, 78 (15,5%) HER- positive and 421 (83.7%) were Ki-67-high (>20%). The simple kappa coefficient was for ER = 0.7938, PR = 0.6540, HER2=0.8172 and Ki-67=0.3655. This implies that the ER, PR and HER2 measurements show a high correlation between both methods, whereas the Ki-67 measurement does not. The accuracy between the STRAT4 and IHC was 89.7% for ER, 83.3% for PR, 94.6% for HER2 and 86.7% for Ki-67. Conclusions: Our results show a high concordance between standardized central IHC and automated mRNA expression analysis for the most important BC biomarkers ER, PR and HER2. For the continuous proliferation marker Ki-67, the concordance is slightly lower. The STRAT4 assay might offer an additional option to conventional methods for BC biomarker assessment, in particular in situations where ICH is not feasible. To determine the clinical validity, additional outcome analyses are necessary. Clinical trial identification: GeparX NCT02682693. Legal entity responsible for the study: GBG Forschungs GmbH. Funding: The clinical trial was supported by Celgene and Amgen and this study by Cepheid. Disclosure: All authors have declared no conflicts of interest.
ORAL SULFATE SOLUTION IN OBESE PATIENTS AS PREPARATION FOR COLONOSCOPY: A PROSPECTIVE, MULTICENTER, NONINFERIORITY TRIAL
Authors: HS Lee, EY Kim, ES Kim, SK Kim, YJ Lee, HJ Lee, BI Jang, KO Kim, CH Yang, YS Hwan, YG Kim
Journal: Endoscopy (2019)

Obesity might be related to inadequate bowel preparation with conventional lavage solution. A new formulation of oral sulfate solution (OSS, Suclear) showed effective bowel preparation compared with a standard 4L polyethylene glycol regimen in general population. However, there is no study on bowel preparation with OSS in obese patients. We investigated whether OSS is effective in obese patients as bowel preparation for colonoscopy.
A Phase I Study of FLX925, a Dual FLT3 and CDK4/6 Inhibitor in Patients with Relapsed or Refractory Acute Myeloid Leukemia (AML)
Authors: Naval Daver, Daniel A. Pollyea, David A. Rizzieri, Jeanne Palmer, Raajit K. Rampal, Shira Dinner, Dale L. Bixby, Mary-Elizabeth M. Percival, Tibor Kovacsovics, Kebede H. Begna, Alexander E. Perl, Marina Konopleva, Lisa Seitz, Jenny McKinnell, Daniel T Johnson, William Ho, Jorge E. Cortes
Journal: Blood (2017)
MUCOSAL FLATTENING ASSISTED COLONOSCOPY (FAC) FOR IMPROVING ADENOMA DETECTION RATE: A SYSTEMATIC REVIEW WITH PAIRWISE AND NETWORK META-ANALYSIS
Authors: C Marmo, S Thayalasekaran, B Pradeep, P Gkolfakis, K Triantafyllou, C Hassan, R Marmo
Journal: Endoscopy (2019)

Improving ADR is currently the central focus of quality improvement in colonoscopy. Fold flattening devices could ameliorate the ADR. Aims of study; to compare efficacy of mucosal flattening assisted colonoscopy vs. standard colonoscopy in improving adenoma detection rate.
UK’s “austerity experiment” has forced millions into poverty and homelessness, say UN rapporteur
Authors: Sophie Arie
Journal: BMJ (2019)

The United Nations has accused the UK government of unnecessarily causing a “social calamity” with an “austerity experiment” which has forced millions of people into poverty, causing record levels of hunger, homelessness, and decreased life expectancy for some.

But the government has rejected the findings, insisting that the country is “one of the happiest places in the world.”

“UK standards of wellbeing have descended precipitately in a remarkably short period of time, as a result of deliberate policy choices made when many other options were available,” said Philip Alston, the UN’s special rapporteur on extreme poverty and human rights, in a report published on 22 May.1

In the world’s fifth largest economy, there are 14 million people—a fifth of the population—living in …
SINGLE-OPERATOR PERORAL CHOLANGIOPANCREATOSCOPY-GUIDED LITHOTRIPSY FOR DIFFICULT BILIARY AND PANCREATIC STONES – A PROSPECTIVE MULTICENTER STUDY
Authors: J Fernandes, T Araújo, G Alexandrino, L Lourenço, P Barreiro, D Horta, M Moreira, H Ribeiro, S Giestas, F Lucas, D Libânio, J Reis, T Bana e Costa, M Certo, L Lopes, J Canena
Journal: Endoscopy (2019)

ERCP is the first choice for the removal of biliary and pancreatic stones. In difficult stones, advanced therapeutic techniques, such as electrohydraulic lithotripsy (EHL) and laser lithotripsy (LL) have been proposed. Recently, the availability of single-operator cholangiopancreatoscopy (SOCP) turned these techniques more accessible and easier to perform. We sought to evaluate the clinical efficacy and safety of SOCP guided-lithotripsy using EHL/LL in patients with complex biliary and pancreatic stones.
Variation Among Primary Care Physicians in 30-Day Readmissions
Authors: Siddhartha Singh, James S. Goodwin, Jie Zhou, Yong-Fang Kuo, Ann B. Nattinger
Journal: Annals of Internal Medicine (2019)

Whether readmission rates vary by primary care physician (PCP) is unknown, although federal policy holds PCPs accountable for reducing readmissions.To determine whether 30-day readmission rates vary by PCP.Retrospective cohort study using marginal models and multilevel logistic regression with 100% of data on Texas Medicare claims from 2008 to 2015.Texas.Patients discharged alive between 1 January 2008 and 30 November 2015 who had a PCP in the prior year and whose PCP had at least 50 admissions in the study period.Readmission within 30 days of discharge. Follow-up visits with a PCP within 7 days of discharge were also measured.Between 2012 and 2015, the mean risk-standardized rate of 30-day readmissions was 12.9%. Of 4230 PCPs, 1 had a readmission rate that was significantly higher than the mean and none had a significantly lower rate. The 10th and 90th percentiles of PCP readmission rates were 12.4% and 13.4%, respectively, each only 0.5 percentage point different from the mean. The 99th percentile of PCP readmission rates was 14.0%, 1.1 percentage points higher than the mean. Detecting a 1.1-percentage point difference from the mean adjusted readmission rate would require more than 3500 admissions per PCP per year.Only fee-for-service Medicare patients in a single state were included. The authors could not account for confounders not included in Medicare databases or classify readmissions as avoidable.Variation in readmission rates among PCPs is very low. Programs holding PCPs accountable for readmissions may prove ineffective.National Institutes of Health.
Should funders driving for universal open access in research be obliged to ensure freedom of publication for all?
Authors: Jonathan P Sturgeon
Journal: BMJ (2019)

Large funders are moving to enforce open access to their research.1 The Wellcome Trust’s open access policy will change on 1 January 2020 to fund only article processing charges (APCs) in fully open access journals, deliberately not funding open access charges in hybrid journals.2 The aim of this change is to support a transition to a fully open access world. This policy is …
Abstract 16186: Hypoxic Pre-conditioning on Human CD34+ Stem Cells Enhances Exosome Therapeutics of Ischemic Tissue Repair Through ETS-1-Regulated Pathway
Authors: Yaxuan Liang, Prabhu Mathiyalagan, David Kim, Douglas Losordo, Roger Hajjar, Susmita Sahoo
Journal: Circulation (2015)

Previous studies in our lab have revealed a novel mechanism that therapeutically important human CD34+ stem cells secrete exosomes (Exo) to extracellular milieu that induce angiogenic activity independent of the cells. Further studies demonstrated that CD34+ exosomes (CD34Exo) carry and transfer of proangiogenic miRNAs, such as miR-126, which affect the therapeutic function of the exosomes. Herein we hypothesized that hypoxic treatment of CD34+ stem cells can modulate the miRNA content and regenerative efficacy of CD34Exo. Methods and Results: Exosomes from human CD34+ cells cultured under hypoxia (H-Exo) were more proliferative, anti-apoptotic and angiogenic in vitro, as compared to exosomes from cells under normoxia (N-Exo). In a mouse model of hind limb ischemia, H-Exo treatment significantly enhanced perfusion (ratio: 0.93±0.05 v 0.77±0.02), increased capillary density (1.6±0.2 v 1.1±0.1/HPF) and prevented ischemic limb amputation (0% v 37.5%) as compared to N-Exo (p&lt;0.05; n=7-8). Flow cytometry and confocal microscopy indicated that H-Exo was uptaken by endothelial cells in the ischemic limb. Interestingly, hypoxic treatment did not alter the size and quantity of Exo or expression of major proteins of CD34Exo compared with normoxic treatment. However, hypoxic treatment altered the proangiogenic miRNA expression in H-Exo including miR-210 and miR-126. ETS-1, a transcription factor induced by hypoxia-inducible fator-1 (HIF-1) is known to regulate expression of miR-126. We have examined the protein and RNA expression of HIF-1 and ETS-1 in Sca-1 positive mouse hematopoietic stem cells, and propose that HIF-1/ETS-1 regulatory mechanisms affect the expression of exosomal miR-126 under hypoxia. These results are being confirmed in human CD34+ cells using siRNA silencing and HIF hydroxylase inhibitor dimethyloxalylglycine. Conclusion: Hypoxia induced miR-126 expression in CD34 cell-derived exosomes stimulating exosomes-mediated angiogenesis and therapeutic recovery via ETS-transcriptional pathway. Our work has important clinical implications for therapeutic angiogenesis, especially in diabetic and cardiovascular patients who have stem cells with diminished angiogenic potential.