tbuckley/cabot-search huggingface dataset:
Bone Sequestration as a Consequence of Esophageal Carcinoma Metastasis Detected by 18F-FDG PET/CT
Authors: Futao Cui, Minggang Su, Chunmeng Chen, Rong Tian
Journal: Clinical Nuclear Medicine (2018)

A bony sequestrum is a single piece of bone present in an area of osteolysis. It is separated from the surrounding bone and is primarily observed in patients with bone infection. We present our radiographic findings on F-FDG PET/CT in a case of esophageal squamous cell carcinoma with a sequestrum in the skull metastasis.
Ultra-low-dose CT detects synovitis in patients with suspected rheumatoid arthritis
Authors: Torsten Diekhoff, Sevtap Tugce Ulas, Denis Poddubnyy, Udo Schneider, Sandra Hermann, Robert Biesen, Gerd R Burmester, Bernd Hamm, Kay Geert Hermann
Journal: Annals of the Rheumatic Diseases (2018)

Purpose To prove the feasibility and measure the diagnostic accuracy of contrast-enhanced ultra-low-dose CT (ULD-CT) for the depiction of inflammatory soft-tissue changes (synovitis, tenosynovitis and peritendonitis) in patients with arthritis of the hand. Materials and methods In this institutional review board–approved study, 36 consecutive patients over the age of 50 with suspected rheumatoid arthritis underwent ULD-CT (estimated radiation exposure &lt;0.01 mSv) and MRI of the hand with weight-adapted intravenous contrast administration. ULD-CT subtraction and MR images were assessed for synovitis, tenosynovitis and peritendonitis by three readers using a modified Rheumatoid Arthritis MRI Score (RAMRIS). Patients were asked which modality they would prefer for future examinations. Sensitivity and specificity of ULD-CT for detection of inflammatory changes were calculated using MRI as standard of reference. The sum scores were correlated using Pearson’s r. Results All 36 patients showed synovitis in MRI. ULD-CT had 69% sensitivity on the patient level and 65% on the joint level with 87% specificity. Sensitivity was higher in patients with more severe inflammation (80% for MRI RAMRIS &gt;1). There was almost perfect correlation between the modified RAMRIS sum scores of ULD-CT and MRI (Pearson’s r=0.94). Regarding preferences for future examinations, 85% preferred ULD-CT over MRI. ULD-CT detected more differential diagnoses than MRI (8 vs 2/12). Conclusion Contrast-enhanced ULD-CT of the hand allows for depiction of soft-tissue inflammation at the hand and can be achieved using very low radiation exposure (&lt;0.01 mSv). ULD-CT may evolve to a fast and comfortable alternative to MRI, although it is not as sensitive as MRI for detecting mild disease.
Abstract P055: Cooking Methods for Meats and Risk of Type 2 Diabetes: Results From Three Prospective Cohort Studies
Authors: Gang Liu, Geng Zong, Yang Hu, Frank B Hu, Walter C Willett, David Eisenberg, Qi Sun
Journal: Circulation (2017)

Importance: The role of high-temperature cooking methods (broiling, barbequing, or roasting) on the association of meat consumption with risk of type 2 diabetes (T2D) is unknown. Objective: To examine cooking methods for meats (chicken, fish, and red meat) in relation to T2D risk among men and women who consumed meats regularly (≥2 servings/week). Design, Setting, and Participants: The prospective studies included 52,720 women from the Nurses’ Health Study (NHS 1996-2012), 60,809 women from the Nurses’ Health Study II (NHS II 2001-2013), and 24,679 men from the Health Professionals Follow-Up Study (HPFS 1996-2012) who were free of diabetes, cardiovascular disease, and cancer at baseline. Main Outcomes and Measures: Incident cases of T2D were identified through self-report and confirmed by validated supplementary questionnaires. Results: We documented 7,893 incident T2D cases during 1.74 million person-years of follow up. After multivariate adjustment of demographics, lifestyle factors, and total intake of chicken, fish, and red meat, a higher frequency of high-temperature cooking of meats was independently associated with an increased T2D risk. When comparing &gt;15 times/month with &lt;4 times/month, the hazard ratios (HRs) and 95% confidence intervals (CIs) of T2D were 1.36 (1.22, 1.52; P trend&lt;0.001) in NHS, 1.82 (1.56, 2.12; P trend&lt;0.001) in NHS II, and 1.10 (0.90, 1.36; P trend=0.78) in HPFS; and the pooled HR was 1.43 (1.32, 1.56; P trend &lt;0.001). The results remained significant when analyzing by source of meats; and the pooled HRs (95% CI) were 1.64 (1.49, 1.81; P trend &lt;0.001) for red meat and 1.22 (1.13, 1.32; P trend &lt;0.001) for white meat. In addition, a higher frequency of high-temperature cooking of meats was associated with greater weight gain and higher risk of obesity, especially among women. Mediational analyses showed that the significant associations of high-temperature cooking with T2D risk were partially explained by changes in body mass index (41.6% in NHS and 46.6% in NHS II) in women. Conclusions and Relevance: Our results suggest that, independent of meat consumption, high-temperature cooking methods may further increase diabetes risk, especially in women.
Abstract 13831: Atrial and Ventricular Cardiac Stem Cells From the Same Heart Exhibit Differential Functional Characteristics for Cardiac Regeneration but Are Superior to the Endothelial Progenitor Cells From the Same Patient
Authors: Parul Dixit, Hayden Donnelly, Midori Edamatsu, Ivor Galvin, Richard Bunton, Rajesh Katare
Journal: Circulation (2015)

Introduction: Deciding the best cell type for cardiac regeneration remains a challenge, however, no studies have directly compared the functional efficacy of cardiac stem cells (CSCs) with extra- cardiac SCs isolated from the same patient. Objective: To compare the functional characteristics of endothelial progenitor cells (EPCs), right atrial (RAA) CSCs and left ventricular (LV) CSCs isolated from the same patients. Methods and Results: Flow-cytometry analysis of CSCs (n=12 patients) revealed higher expression of CD90 (involved in cell adhesion and migration) in RAA CSCs (CD90 &amp; CD105 ++ve cells: 71±15% in RAA vs. 47±27% in LV, P&lt;0.05). However, scratch assay showed superior wound closure in LV CSCs (80±10% in LV vs. 60±5% in RAA, P&lt;0.05) suggesting that LV CSCs have a better migration potential. Moreover, the expansion properties of RAA CSCs were better than LV CSCs in terms of higher cumulative population doublings in culture. To simulate in vivo ischemic environment, cells were subjected to hypoxia (1% O2) and serum starvation for 3 days. RAA and LV CSCs exhibited similar pattern of resistance to apoptotic cell death (evaluated as percentage of annexin +ve cells, n=5) and proliferation under hypoxia. Interestingly, EPCs exhibited highest resistance to apoptotic cell death, but they also showed the lowest proliferation under hypoxia (P&lt;0.05). Secretion of paracrine and pro-angiogenic factors have been thought to be most important mechanisms behind cardiac regeneration. Therefore, to compare the paracrine angiogenic and wound healing potential, HUVECs were cultured in culture supernatant (CS) from all the 3 cell types. RAA-CS showed the highest increase in tube formation capacity (P&lt;0.05, n=6), while the scratch assay showed comparable wound closure with both LV and RAA CS (67.56 ± 7.36% and 70.02 ± 5.70%, n=5), but was lowest in EPC CS (54±7%). The secretion of the angiogenic growth factor VEGF-A (n=5) was lowest in EPCs (0.36± 0.20 ng/mL) and comparable between RAA (3.44±1.94 ng/mL) and LV CSCs (4.33± 1.57 ng/mL). Conclusion: Stem cells from different regions exhibit differential functional characteristics within the same patient. The selection of the best cell type should therefore be influenced by the nature of the injury and the type of effect desired.
Are real-world patient-reported outcomes associated with survival in patients with advanced pancreatic cancer?
Authors: Wei Fang Dai, Jaclyn Marie Beca, Helen Guo, Lucy Qiao, Wanrudee Isaranuwatchai, Deborah Schwartz, Rohini Naipaul, Jessica Arias, Scott Gavura, Lisa Catherine Barbera, Kelvin K. Chan
Journal: Journal of Clinical Oncology (2018)

205 Background: Advanced pancreatic cancer (APC) patients often have a substantial symptom burden. In Ontario, patients visiting cancer clinics routinely complete the Edmonton Symptom Assessment Scale (ESAS), which screens for 9 symptoms (scale: 0-10). Using ESAS, we explored the association between baseline patient-reported outcomes and overall survival (OS). Methods: APC Patients with ESAS records prior to receiving publicly-funded drugs from November 2008 to March 2016 were identified from Cancer Care Ontario’s New Drug Funding Program and Symptom Management databases. We examined 3 baseline composite ESAS scores: Total Symptom Distress Score (TSDS: all 9 symptoms), Physical Symptom Score (PHS: 6/9 symptoms), and Psychological Symptom Score (PSS: 2/9 symptoms); Composite scores greater than a threshold (defined as number of symptoms in composite score multiplied by clinically relevant score (≥4)) were categorized as High Symptom Burden (TSDS ≥ 36, PHS ≥ 24, PSS ≥ 8). The primary endpoint, OS, was assessed using Kaplan-Meier. Multivariable Cox models were used to adjust for age, gender, income, prior therapies (surgery, adjuvant gemcitabine, radiation), and Charlson's comorbidity. Analysis was repeated in a sub-cohort with identifiable ECOG status and stage. Results: We identified 2,199 APC patients (mean age 64 years, 55% male) with ESAS records prior to receiving gemcitabine (54%), FOLFIRINOX (40%) or gemcitabine/nab-paclitaxel (6%). Crude median survival was 4.5 and 7.3 months for patients with high and low TSDS burden, respectively (HR = 1.50, 95% CI: 1.36, 1.66). After adjustment with multivariable Cox model, high TSDS burden was associated with lower OS (HR = 1.47, 95% CI: 1.33, 1.63). Similar trends were observed for PHS and PSS. When adjusting for both PHS and PSS in a Cox model, only the effect of PHS remained significant. In the sub-cohort (n = 393), high TSDS burden (HR = 1.34, 95% CI: 1.04, 1.73) was associated with lower OS, after adjusting for ECOG and stage. Conclusions: Among APC patients, a higher burden of patient-reported symptoms, via ESAS, at baseline was associated with reduced OS. The effect was prominent for physical symptoms, even after adjusting for treatment, stage and ECOG.
Snail promotes metastasis of nasopharyngeal carcinoma partly by down‐regulating TEL2
Authors: Yi Sang, Chun Cheng, Yi‐Xin Zeng, Tiebang Kang
Journal: Cancer Communications (2018)

Abstract Background Metastasis is the major cause of treatment failure in patients with nasopharyngeal carcinoma (NPC). We previously reported that TEL2, a negative regulator of SERPINE1, could inhibit NPC metastasis to lymph nodes. Method A series of in vivo and in vitro assays were performed to elucidate the regulation between Snail and TEL2. TEL2 expression was analyzed in three representative NPC cell lines expressing low levels of Snail (S26, 6‐10B, HK1) and two cell lines expressing high levels of Snail (S18, 5‐8F). Luciferase and chromatin immunoprecipitation assays were used to analyze the interaction between Snail and TEL2. The roles of the Snail/TEL2 pathway in cell migration and invasion of NPC cells were examined using transwell assays. Metastasis to the lungs was examined using nude mouse receiving NPC cells injection through the tail vein. Results Ectopic Snail expression down‐regulated TEL2 at the mRNA and protein levels, whereas knockdown of Snail using short hairpin RNA up‐regulated TEL2. Luciferase and chromatin immunoprecipitation assays indicated that Snail binds directly to the TEL2 promoter. Ectopic Snail expression enhanced migration and invasion of NPC cells, and such effects were mitigated by TEL2 overexpression. TEL2 overexpression also attenuated hypoxia‐induced cell migration and invasion, and increased the number of metastatic pulmonary nodules. Snail overexpression reduced the number of metastatic pulmonary nodules. Conclusions TEL2 is a novel target of Snail and suppresses Snail‐induced migration, invasion and metastasis in NPC.
Social patterning of telephone health-advice for diarrhoea and vomiting: analysis of 24 million telehealth calls in England
Authors: Natalie L. Adams, Tanith C. Rose, Alex J. Elliot, Gillian Smith, Roger Morbey, Paul Loveridge, James Lewis, Gareth Studdard, Mara Violato, Sarah J. O'Brien, Margaret Whitehead, David C. Taylor-Robinson, Jeremy I. Hawker, Benjamin Barr
Journal: Journal of Infection (2018)

Gastrointestinal (GI) infections are common and most people do not see a physician. There is conflicting evidence of the impact of socioeconomic status (SES) on risk of GI infections. We assessed the relationship between SES and GI calls to two National Health Service (NHS) telephone advice services in England.
Sequential high-dose cytarabine and mitoxantrone (S-HAM) versus standard double induction in acute myeloid leukemia—a phase 3 study
Authors: Jan Braess, Susanne Amler, Karl-Anton Kreuzer, Karsten Spiekermann, Hans Walter Lindemann, Eva Lengfelder, Ullrich Graeven, Peter Staib, Wolf-Dieter Ludwig, Harald Biersack, Yon-Dschun Ko, Michael J. Uppenkamp, Maike De Wit, Stefan Korsten, Rudolf Peceny, Tobias Gaska, Xaver Schiel, Dirk M. Behringer, Michael G. Kiehl, Bettina Zinngrebe, Gerald Meckenstock, Eva Roemer, Dirk Medgenberg, Ernst Spaeth-Schwalbe, Gero Massenkeil, Heidrun Hindahl, Rainer Schwerdtfeger, Guido Trenn, Cristina Sauerland, Raphael Koch, Martin Lablans, Andreas Faldum, Dennis Görlich, Stefan K. Bohlander, Stephanie Schneider, Annika Dufour, Christian Buske, Michael Fiegl, Marion Subklewe, Birgit Braess, Michael Unterhalt, Anja Baumgartner, Bernhard Wörmann, Dietrich Beelen, Wolfgang Hiddemann
Journal: Leukemia (2018)

Dose-dense induction with the S-HAM regimen was compared to standard double induction therapy in adult patients with newly diagnosed acute myeloid leukemia. Patients were centrally randomized (1:1) between S-HAM (2nd chemotherapy cycle starting on day 8 = "dose-dense") and double induction with TAD-HAM or HAM(-HAM) (2nd cycle starting on day 21 = "standard"). 387 evaluable patients were randomly assigned to S-HAM (N = 203) and to standard double induction (N = 184). The primary endpoint overall response rate (ORR) consisting of complete remission (CR) and incomplete remission (CRi) was not significantly different (P = 0.202) between S-HAM (77%) and double induction (72%). The median overall survival was 35 months after S-HAM and 25 months after double induction (P = 0.323). Duration of critical leukopenia was significantly reduced after S-HAM (median 29 days) versus double induction (median 44 days)—P < 0.001. This translated into a significantly shortened duration of hospitalization after S-HAM (median 37 days) as compared to standard induction (median 49 days)—P < 0.001. In conclusion, dose-dense induction therapy with the S-HAM regimen shows favorable trends but no significant differences in ORR and OS compared to standard double induction. S-HAM significantly shortens critical leukopenia and the duration of hospitalization by 2 weeks.
Development of the CCRU kit squad: Centralization of biospecimen “kit” management.
Authors: Vanessa Speers
Journal: Journal of Clinical Oncology (2018)

295 Background: Personalized medicine has resulted in a rapid increase in biospecimens collection. Each biospecimen collected requires supplies that are provided in the form of “kits”. The number of kit types per protocol ranges anywhere from 2-60, with an average of 30 different kit types per trial. Historically, each trials nurse has managed their own kits resulting in large amounts of nursing time being spent on kit management. Kits took up a large amount of space in clinical areas, including expired kits, and they were being managed in no standardized fashion. Due to rapidly increasing biospecimen volumes, existing methods of kit management were no longer feasible and the CCRU Kit Squad was developed. Methods: Over the course of 12-mos, an extensive assessment of current kit management practices were reviewed with all disease site groups, including workflows and quantities utilized. An e-commerce software platform was selected, and semi-customized to centralize online ordering and receiving of kits, and the creation of a central location was setup for kit storage and daily operations. On-boarding of each group included retrieving existing kits from each nurse, uploading kits to the software, training each nurse to use the software, setting up accounts with each respective vendor for deliveries and re-supply, and disposing of expired kits. Results: Disease site groups were transitioned to the CCRU Kit Squad stepwise from Oct 2016 to Dec 2017 (15-mos), which included 80 nurses, 16 disease site groups, and over 400 clinical trials. By the end of 2017, the average number of kits ordered per day, and per month were 33 and 1003, respectively. Conclusions: The CCRU Kit Squad developed a centralized online service for kit management, thereby reducing administrative burden on clinical trial nurses. It has streamlined the management of biospecimen kits, eliminated wasted space in clinical areas, and facilitated the selection of the right kit for the right test at the right time.
A Previously Unrecognized Ca<sup>2+</sup>‐inhibited Nonselective Cation Channel in Red Blood Cells
Authors: Polina Petkova‐Kirova, Laura Hertz, Asya Makhro, Jens Danielczok, Rick Huisjes, Esther Llaudet‐Planas, Maria del Mar Mañú‐Pereira, Joan‐Luis Vives Corrons, Richard van Wijk, Anna Bogdanova, Lars Kaestner
Journal: HemaSphere (2018)

Supplemental Digital Content is available in the text.
Abstract 19733: Shear-Dependent Aortic Valve Endothelial Inflammation and Calcification Are Regulated by O-GlcNAc Modification of MEF2C Transcription Factor
Authors: Jack Heath, Hanbyeol Kim, Joan Fernandez Esmerats, Rachel Simmons, Sandeep Kumar, Jinwon Cho, Hanjoong Jo
Journal: Circulation (2016)

Introduction: Aortic valve (AV) disease is a significant contributor to cardiovascular mortality. AV calcification occurs preferentially on the fibrosa side, where endothelial cells (ECs) are subje...
Abstract 14104: Replacement of Infarct Myocardium by Large Scale-Expanded Human Induced Pluripotent Stem Cell-Derived Cardiac Cell-Sheet in a Porcine Chronic Myocardial Infarction Model
Authors: Keitaro Domae, Shigeru Miyagawa, Satsuki Fukushima, Atsuhiro Saito, Yukiko Imanishi, Maki Takeda, Emiko Ito, Tsuyoshi Ishikawa, Nobu Miyagawa, Katsuhisa Matsuura, Masahiro Kino-oka, Koichi Toda, Yoshiki Sawa
Journal: Circulation (2015)

Introduction: It has been shown that transplanted induced pluripotent stem cell (iPSC)-derived cardiac cells in the myocardial infarction (MI) heart synchronously contract with native myocardium to mechanically contribute to functional recovery in rodent models. We herein hypothesized that large scale cardiac cell-sheets generated by human iPSCs may induce a greater functional recovery than small scale ones after transplantation in chronic MI heart. Methods: Bioreactor-based three-dimensional suspension culture system was used for generating large scale-expanded human iPSC-derived cardiomyocytes, of which cardiac troponin T positivity was constantly 75-85%. Scaffold-free cell-sheets containing several cell number (1.0х10^6, 10^7, 10^8) were transplanted over the cardiac surface in porcine chronic MI heart (n=5 each). Tacrolimus and prednisolone were daily given in all pigs against xeno-transplantation-inducing immune reaction. Results: Echocardiographically, left ventricular systolic and diastolic dimensions were significantly decreasing and ejection fraction was significantly increasing in the 10^8 cell group. In addition, global myocardial structure was better preserved in the 10^8 cell group with presence of the graft in the infarct area macroscopically (Figure). Moreover, there were significantly less accumulation of interstitial fibrosis in the infarct-remote area and greater vascular density and expression of VEGF, bFGF, and SDF-1 in the infarct-border area in the 10^8 cell group than the other groups at 3 months after the transplantation. Conclusions: Large scale human iPSC-derived cardiac cells were engrafted in the infarct myocardium, showing substantial functional recovery in a porcine chronic MI heart, indicating that artificial cell-based myocardial replacement therapy may be achieved. In contrast, small scale cardiac cells induced modest functional recovery, suggesting paracrine mechanisms of this treatment.
Detection of serrated polyps: How do endoscopists rate?
Authors: Joseph Anderson
Journal: Endoscopy (2018)

See also: Endoscopist factors that influence serrated polyp detection: a multicenter studyEndoscopy eFirstDOI: 10.1055/a-0597-1740 See also: Detection of clinically relevant serrated polyps during screening colonoscopy: results from seven cooperating centers within the German colorectal screening programEndoscopy eFirstDOI: 10.1055/a-0598-4477
Sixteen diverse laboratory mouse reference genomes define strain-specific haplotypes and novel functional loci
Authors: Jingtao Lilue, Anthony G. Doran, Ian T. Fiddes, Monica Abrudan, Joel Armstrong, Ruth Bennett, William Chow, Joanna Collins, Stephan Collins, Anne Czechanski, Petr Danecek, Mark Diekhans, Dirk-Dominik Dolle, Matt Dunn, Richard Durbin, Dent Earl, Anne Ferguson-Smith, Paul Flicek, Jonathan Flint, Adam Frankish, Beiyuan Fu, Mark Gerstein, James Gilbert, Leo Goodstadt, Jennifer Harrow, Kerstin Howe, Ximena Ibarra-Soria, Mikhail Kolmogorov, Chris J. Lelliott, Darren W. Logan, Jane Loveland, Clayton E. Mathews, Richard Mott, Paul Muir, Stefanie Nachtweide, Fabio C. P. Navarro, Duncan T. Odom, Naomi Park, Sarah Pelan, Son K. Pham, Mike Quail, Laura Reinholdt, Lars Romoth, Lesley Shirley, Cristina Sisu, Marcela Sjoberg-Herrera, Mario Stanke, Charles Steward, Mark Thomas, Glen Threadgold, David Thybert, James Torrance, Kim Wong, Jonathan Wood, Binnaz Yalcin, Fengtang Yang, David J. Adams, Benedict Paten, Thomas M. Keane
Journal: Nature Genetics (2018)

We report full-length draft de novo genome assemblies for 16 widely used inbred mouse strains and find extensive strain-specific haplotype variation. We identify and characterize 2,567 regions on the current mouse reference genome exhibiting the greatest sequence diversity. These regions are enriched for genes involved in pathogen defence and immunity and exhibit enrichment of transposable elements and signatures of recent retrotransposition events. Combinations of alleles and genes unique to an individual strain are commonly observed at these loci, reflecting distinct strain phenotypes. We used these genomes to improve the mouse reference genome, resulting in the completion of 10 new gene structures. Also, 62 new coding loci were added to the reference genome annotation. These genomes identified a large, previously unannotated, gene (Efcab3-like) encoding 5,874 amino acids. Mutant Efcab3-like mice display anomalies in multiple brain regions, suggesting a possible role for this gene in the regulation of brain development.