tbuckley/cabot-search huggingface dataset:
A multi-marker prognostic to assess risk of invasive recurrence in DCIS patients.
Authors: Troy Bremer, Steven Paul Linke, Pat W. Whitworth, Rakesh Patel, Todd Barry, Stephen Lyle, Karl Simin, Karin Jirstrom, Fredrik Warnberg
Journal: Journal of Clinical Oncology (2016)

1019 Background: Ductal carcinoma in situ (DCIS) is a heterogeneous disease associated with a spectrum of risk for ipsilateral breast events (IBE). Reducing overtreatment is an important unmet need for DCIS patients. Methods: Patients were from Uppsala University Hospital diagnosed 1986 - 2004, and University of Massachusetts diagnosed 1999 -2008, treated with breast conserving surgery (BCS) with (56%) or without (44%) radiation therapy (RT). Biomarkers (p16/INK4A, Ki-67, COX-2, PgR, HER2, FOXA1, SIAH2 via IHC/ISH) were assessed in FFPE tissue by board-certified pathologists. Pathological and clinical data were collected from medical records. A multi-marker based prognostic was developed on the combined patient sets (n = 600, 8.1 year median follow-up) using multiple cross-validation (patients divided into independent training and testing subsets). Patients with DCIS detected by mammography screening (n = 379) were then stratified into risk categories defined by the multi-marker based prognostic or clinicopathologic risk (“not low” defined as Size > 2.5 cm or Grade 3). Ten-year invasive IBE outcomes were assessed using Kaplan-Meier and Cox proportional hazards analyses. Results: Size/Grade did not significantly differentiate invasive risk. However, the multi-marker based prognostic stratified patients treated without RT (p < 0.001). Patients with “low” multi-marker invasive risk treated without RT had only a 5% (+/- 5%) 10-yr invasive IBE rate. Conclusions: The multi-marker prognostic identified patients at different risks for invasive IBEs in cross-validation. Patients in the “low” multi-marker risk category had a low invasive event rate regardless of RT. The value of this DCIS prognostic is being evaluated in multiple independent validation studies. 10-year invasive ipsilateral risk. BCS, No RT BCS, RT Risk±95% CI Prevalence N Risk±95% CI Prevalence N Baseline Invasive Risk 11% ±5% 39% 150 6% ±4% 56% 229 Size/Grade Group “Low” 10% ±6% 66% 99 4% ±5% 44% 102 Size/Grade Group not “Low” 15% ±11% 34% 51 7% ±5% 56% 127 Biomarker Assessment “Low” 5% ±5% 73% 110 6% ±5% 73% 168 Biomarker Assessment not “Low” 28% ±13% 27% 40 6% ±7% 27% 61
Poor Quality of Life Predicts Adherence to a Weight-Loss Intervention in Overweight and Obese Patients With Heart Failure
Authors: Marjan Motie, Terry A Lennie, Lorraine S Evangelista
Journal: Circulation (2013)

CjrculatjoD CORE 2. EPIDEM(OLOGY AND PREVENTION OF CV DISEASE: PHYSIOLOGY, PHARMACOLOGY AND LIFESTYLE SESSION TITLE: CARDIOMETABOLIC EFFECTS OF POPULAR DIETS Abstract 18759: Poor Quality of Life Predicts Adherence to a Weight-Loss Intervention in Overweight and Obese Patients With Heart Failure Marjan Motie, Terry A Lennie and Lorraine S Evangelista Published: November 26, 2013 Article Info & Metrics eletters ... Jump to Abstract Background: Poor quality of life (QOL) has a known association with cardiometabolic risk that is also correlated with weight, diet, physical activity, and smoking. However, the effect of QOL on adherence (i.e. completing the study protocol) to a dietary intervention in heart failure (HF) patients has not been studied. We investigated the relationship between QOL and adherence with completing a 3 month intensive weight loss intervention in a cohort of obese HF patients with metabolic complications and tested a model that included age, gender, race, baseline weight, functional status, and QOL on adherence. Methods: Data on QOL of overweight and obese patients with HF who participated in a larger clinical trial comparing a high protein and standard protein diet were collected at baseline and 3 months using the Minnesota Living with Heart Failure (MLHF) Questionnaire. Comparisons were made between participants who completed the 3 month dietary intervention (i.e. completers) and participants who did not (i.e. non-completers). Results: Forty-nine patients - mean age 59.1 ± 9.8; weight 248.8 ± 29.7 pounds; EF 37.3 ± 12.5%; peak V02 12.5 ± 3. 7 mg/kg/ml; 55% White; 20% Hispanics; 16% Blacks; 8% Asians - participated in the study; 34 (70%) completed the intensive phase of the dietary intervention. There were statistically significant differences in QOL
Cluster Regulation of RUNX Family By "Gene Switch" Triggers a Profound Tumor Regression of Diverse Origins
Authors: Ken Morita, Kensho Suzuki, Shintaro Maeda, Yoshihide Mitsuda, Ayaka Yano, Yoshimi Yamada, Hiroki Kiyose, Chieko Tokushige, Paul P. Liu, Souichi Adachi, Hiroshi Sugiyama, Yasuhiko Kamikubo
Journal: Blood (2016)
Structural and Functional Characterization of a Codon Optimized Coagulation Factor VIII
Authors: Svetlana A Shestopal, James H Kurasawa, Jian-Jiang Hao, Elena Karnaukhova, Yideng Liang, Min Lin, Mikhail V Ovanesov, Timothy K Lee, John H McVey, Andrey G Sarafanov
Journal: Blood (2016)
Essential role of CCL21 in establishment of central self-tolerance in T cells
Authors: Mina Kozai, Yuki Kubo, Tomoya Katakai, Hiroyuki Kondo, Hiroshi Kiyonari, Karin Schaeuble, Sanjiv A. Luther, Naozumi Ishimaru, Izumi Ohigashi, Yousuke Takahama
Journal: The Journal of Experimental Medicine (2017)

The chemokine receptor CCR7 directs T cell relocation into and within lymphoid organs, including the migration of developing thymocytes into the thymic medulla. However, how three functional CCR7 ligands in mouse, CCL19, CCL21Ser, and CCL21Leu, divide their roles in immune organs is unclear. By producing mice specifically deficient in CCL21Ser, we show that CCL21Ser is essential for the accumulation of positively selected thymocytes in the thymic medulla. CCL21Ser-deficient mice were impaired in the medullary deletion of self-reactive thymocytes and developed autoimmune dacryoadenitis. T cell accumulation in the lymph nodes was also defective. These results indicate a nonredundant role of CCL21Ser in the establishment of self-tolerance in T cells in the thymic medulla, and reveal a functional inequality among CCR7 ligands in vivo.
Risk of major congenital malformations in relation to maternal overweight and obesity severity: cohort study of 1.2 million singletons
Authors: Martina Persson, Sven Cnattingius, Eduardo Villamor, Jonas Söderling, Björn Pasternak, Olof Stephansson, Martin Neovius
Journal: BMJ (2017)

<b>Objective</b>&nbsp;To estimate the risks of major congenital malformations in the offspring of mothers who are underweight (body mass index (BMI) &lt;18.5), overweight (BMI 25 to &lt;30), or in obesity classes I (BMI 30 to &lt;35), II (35 to &lt;40), or III (≥40) compared with offspring of normal weight mothers (BMI 18.5 to &lt;25) in early pregnancy. <b>Design</b>&nbsp;Population based cohort study. <b>Setting</b>&nbsp;Nationwide Swedish registries. <b>Participants</b>&nbsp;1 243 957 liveborn singleton infants from 2001 to 2014 in Sweden. Data on maternal and pregnancy characteristics were obtained by individual record linkages. <b>Exposure</b>&nbsp;Maternal BMI at the first prenatal visit. <b>Main outcome measures</b>&nbsp;Offspring with any major congenital malformation, and subgroups of organ specific malformations diagnosed during the first year of life. Risk ratios were estimated using generalised linear models adjusted for maternal factors, sex of offspring, and birth year. <b>Results</b>&nbsp;A total of 43 550 (3.5%) offspring had any major congenital malformation, and the most common subgroup was for congenital heart defects (n=20 074; 1.6%). Compared with offspring of normal weight mothers (risk of malformations 3.4%), the proportions and adjusted risk ratios of any major congenital malformation among the offspring of mothers with higher BMI were: overweight, 3.5% and 1.05 (95% confidence interval 1.02 to 1.07); obesity class I, 3.8% and 1.12 (1.08 to 1.15), obesity class II, 4.2% and 1.23 (1.17 to 1.30), and obesity class III, 4.7% and 1.37 (1.26 to 1.49). The risks of congenital heart defects, malformations of the nervous system, and limb defects also progressively increased with BMI from overweight to obesity class III. The largest organ specific relative risks related to maternal overweight and increasing obesity were observed for malformations of the nervous system. Malformations of the genital and digestive systems were also increased in offspring of obese mothers. <b>Conclusions</b>&nbsp;Risks of any major congenital malformation and several subgroups of organ specific malformations progressively increased with maternal overweight and increasing severity of obesity. For women who are planning pregnancy, efforts should be encouraged to reduce adiposity in those with a BMI above the normal range.
Loss of Heterozygosity of Chromosome 9p and Loss of P16 INK4A Expression Are Associated with Malignant Gastrointestinal Stromal Tumours
Authors: M Sabah, R Cummins, M Leader, E Kay
Journal: Endoscopy (2004)

Gastrointestinal stromal tumours (GISTs) are distinctive KIT positive mesenchymal neoplasms. The genetic alterations leading to the malignant behaviour of these tumours are not well characterized.
Symptoms in gastrointestinal stromal tumors.
Authors: Loretta A. Williams, Dejka M. Araujo, Qiuling Shi, Nazim N Ali, Hycienth Ahaneku, Kaiyan Jing, Jonathan C. Trent, Charles S. Cleeland
Journal: Journal of Clinical Oncology (2014)

9637 Background: A major barrier to effective symptom management in gastrointestinal stromal tumors (GIST) is lack of recognition of the symptom burden of the disease and treatment. Symptom burden is the combined impact of disease- and treatment-related symptoms on daily functioning. Our aim was to describe the symptom burden of patients with GIST. Methods: After giving IRB-approved informed consent, 150 patients with GIST completed the 20 symptom severity and 6 interference items of the MD Anderson Symptom Inventory for GIST (MDASI-GIST) at least every 2 weeks for 1 year. Symptoms and interference were rated on 0-10 scales (0 = none or no interference, 10 = worst imaginable or complete interference). Patients also answered a single overall quality-of-life (QOL) question every 3 months. Demographic and disease information was collected on all patients. Trajectory analysis determined higher and lower symptom groups. Mixed modeling identified factors predictive of symptom burden. Results: Mean subject age was 59.2 years (standard deviation [sd] = 11.7). 51% (77) of the subjects were female, 83% (124) were white, 47% (70) were employed. Subjects had been diagnosed for an average of 48.3 months (sd = 63.2) and 52% (78) were receiving imatinib. Mean overall QOL rating was 7.7 (best = 10, sd = 2.4). Symptoms reported as most severe over the course of the year were fatigue (mean [M] = 2.95, sd = 2.60), drowsiness (M = 2.30, sd = 2.38), general weakness (M = 2.18, sd = 2.40), disturbed sleep (M = 2.16, sd = 2.46), and muscle soreness/cramping (M = 2.06, sd = 2.41). The mean severity of the 5 most severe symptoms, the interference items, and QOL were all significantly correlated (all P < 0.001). 36.5% of patients were in the higher symptom trajectory group. Younger age, having a primary diagnosis of gastric GIST, and not currently receiving imatinib were predictive of higher symptom burden. Conclusions: Approximately 1/3 of patients with GIST experience higher symptom burden primarily related to fatigue, sleep difficulty, weakness, and muscle discomfort. Higher symptom burden significantly impacts QOL. Additional research is needed to identify effective methods of symptom management. Clinical trial information: NCT01178307.
Tinea in the Time Before Modern Antifungal Agents
Authors: Helena Jenkinson, Beau DiCicco
Journal: JAMA Dermatology (2017)

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Erratum: Epicardial vasomotor responses to acetylcholine are not predicted by coronary atherosclerosis as assessed by intracoronary ultrasound (J. Am. Coll. Cardiol. (1995) 26 (41-49))
Authors: R. A. Nishimura, A. Lerman, J. H. Chesebro, D. M. Ilstrup, D. O. Hodge, S. T. Higano, D. R. Holmes, A. J. Tajik
Journal: Journal of the American College of Cardiology (1995)
Cost Effectiveness of Pre– vs Post–Liver Transplant Hepatitis C Treatment With Direct-Acting Antivirals
Authors: Sumeyye Samur, Brian Kues, Turgay Ayer, Mark S. Roberts, Fasiha Kanwal, Chin Hur, Drew Michael S. Donnell, Raymond T. Chung, Jagpreet Chhatwal
Journal: Clinical Gastroenterology and Hepatology (2017)
Primary operation in synchroneous metastasized invasive breast cancer patients: First oncologic outcomes of the prospective randomized phase III ABCSG 28 POSYTIVE trial.
Authors: Florian Fitzal, Marija Balic, Vesna Bjelic-Radisic, Michael Hubalek, Christian F. Singer, Guenther G. Steger, Christian Marth, Peter Schrenk, Michael Knauer, Anton Haid, Viktor Wette, Irmgard Luisser, Richard Greil, Reinhold Fuegger, Ursula Swoboda, Lidija Soelkner, Michael Gnant
Journal: Journal of Clinical Oncology (2017)

557 Background: The ABCSG 28 Posytive trial compared primary surgery versus primary systemic therapy without surgery in stage IV breast cancer patients. The primary aim was to investigate whether immediate resection of the primary tumor followed by standard systemic therapy improves median survival compared with no surgical resection (NCT01015625). The trial had to be stopped early due insufficient recruitment. Methods: Untreated stage IV breast cancer patients with the primary in situ were randomly assigned to either surgery of the primary versus no surgery followed by systemic therapy between 2011 and 2015 in 15 breast health centers in Austria. Systemic therapy included endocrine therapy or chemotherapy. Patients were routinely followed every 3-6 months. Primary endpoint was median survival. Results: 90 patients (45 with surgery, 45 with primary systemic therapy without surgery) were randomized. Stratification criteria were age, endocrine responsiveness, her2 expression, planned first line therapy and bone only versus other metastases. Patients in the surgery arm had more cT3 breast cancer (22% versus 7%) and more cN2 staging (16% versus 4%) as well as more her2 positive breast cancer cases (27% versus 18%). The median follow up was 37.5 months and immunohistochemical subtype analysis showed 9% basal like, 22% her2 positive, 51% luminal A and 13% luminal B cancers. Both groups were well balanced regarding first line treatment (endocrine versus chemotherapy) however, there were more taxane treated patients in the no surgery group (24.4 versus 15.6%). The median survival in the surgery arm was 34.6 months versus 54.8 months in the no surgery arm without statistical significance (HR 0.691 CI 0.358 – 1.333; p=0.267). Time to distant progression was insignificantly longer in the no surgery arm (surgery arm 13.9 versus no surgery arm 29.0 months). Conclusions: This first analysis of the prospective randomized phase III trial POSYTIVE-ABCSG-28 demonstrated no benefit in overall survival for immediate surgery of the primary in de novo stage IV breast cancer patients. Clinical trial information: NCT01015625.
Abstract 48: Clonal Analysis of Cardiac Cell Generation During Cardiac Development and Injury
Authors: Konstantina Ioanna Sereti, Paniz Kamran, Peng Zhao, Sara Ranjbarvaziri, James Engel, Hanna Mikkola, Reza Ardehali
Journal: Circulation Research (2015)

Accumulating evidence supports limited regenerative potential of the mammalian heart. However, this endogenous regenerative capacity significantly decreases with age and it is not sufficient to replenish the lost myocardium following injury in the adult. Both resident cardiac stem/progenitor cells and mature cardiomyocytes have been proposed to contribute to cardiac tissue generation. Understanding the molecular and cellular mechanisms governing cardiac cell formation is imperative towards the development of novel therapeutic strategies for cardiac regeneration. Hypothesis: Cardiac growth occurs primarily through progenitor cells and to a lesser extent through cardiomyocyte proliferation. Nkx2.5+ cells are the predominant population driving cardiac growth during development and may represent candidate progenitors for cardiac regeneration. Moreover, a subset of “proliferating” αMHC+ cardiomyocytes may also contribute to cardiac growth during early embryonic development and the first week of life. Materials and methods: We performed clonal analysis using a multicolor reporter system (Rainbow) that allows labeling of single cells with one of three fluorescent proteins and retrospective analysis of their progeny. Rainbow mice were crossed to βactinCreER, αMHCCreER, Nkx2.5CreER and Rosa26CreER mice. Tamoxifen was administered at E9.5 or E12.5 and analysis was performed at P1, P7, P15 and P30. Results: We observed significant clonal expansion in βactinCreER;Rainbow and Nkx2.5CreER;Rainbow hearts while αMHCCreER;Rainbow hearts exhibited clones comprising of smaller cell number. We also found that αMHC positive cells lose their proliferative capacity from E9.5 to E12.5, whereas cells expressing Nkx2.5 continue to clonally expand during that same time period. Finally, we demonstrated that αMHC+ cardiomyocyte proliferation is reactivated following myocardial injury soon after birth. Conclusion: Our data support that clonal dominance of progenitor cells promotes cardiac development, while cardiomyocyte proliferation contributes to a lesser extent early in development and postnatally.
Do doctors have a duty to take part in pragmatic randomised trials?
Authors: Marion K Campbell, Charles Weijer, Cory E Goldstein, Sarah J L Edwards
Journal: BMJ (2017)

For society to benefit from new clinical knowledge the expectation should be to participate in research, writes <b>Marion K Campbell</b>; <b>Charles Weijer and colleagues</b> agree but argue that the fundamental need for consent makes this an imperfect duty
Identify new TB cases by screening patients’ household members, research suggests
Authors: Susan Mayor
Journal: BMJ (2017)

Nearly one in 10 people with tuberculosis (TB) diagnosed in England from 2010 to 2012 lived in the same household as another case, a retrospective national cohort study has reported.1

Better screening of people living in the same household as a person with TB could reduce transmission in low incidence countries such as England, recommended researchers from Public Health England, who found that nearly one in …
CCR2-dependent monocyte-derived macrophages resolve inflammation and restore gut motility in postoperative ileus
Authors: Giovanna Farro, Michelle Stakenborg, Pedro J Gomez-Pinilla, Evelien Labeeuw, Gera Goverse, Martina Di Giovangiulio, Nathalie Stakenborg, Elisa Meroni, Francesca D’Errico, Yvon Elkrim, Damya Laoui, Zofia M Lisowski, Kristin A Sauter, David A Hume, Jo A Van Ginderachter, Guy E Boeckxstaens, Gianluca Matteoli
Journal: Gut (2017)

Objective Postoperative ileus (POI) is assumed to result from myeloid cells infiltrating the intestinal muscularis externa (ME) in patients undergoing abdominal surgery. In the current study, we investigated the role of infiltrating monocytes in a murine model of intestinal manipulation (IM)-induced POI in order to clarify whether monocytes mediate tissue damage and intestinal dysfunction or they are rather involved in the recovery of gastrointestinal (GI) motility. Design IM was performed in mice with defective monocyte migration to tissues (C-C motif chemokine receptor 2, Ccr2 −/ − mice) and wild-type (WT) mice to study the role of monocytes and monocyte-derived macrophages (MΦs) during onset and resolution of ME inflammation. Results At early time points, IM-induced GI transit delay and inflammation were equal in WT and Ccr2 − / − mice. However, GI transit recovery after IM was significantly delayed in Ccr2 − / − mice compared with WT mice, associated with increased neutrophil-mediated immunopathology and persistent impaired neuromuscular function. During recovery, monocyte-derived MΦs acquire pro-resolving features that aided in the resolution of inflammation. In line, bone marrow reconstitution and treatment with MΦ colony-stimulating factor 1 enhanced monocyte recruitment and MΦ differentiation and ameliorated GI transit in Ccr2 − / − mice. Conclusion Our study reveals a critical role for monocyte-derived MΦs in restoring intestinal homeostasis after surgical trauma. From a therapeutic point of view, our data indicate that inappropriate targeting of monocytes may increase neutrophil-mediated immunopathology and prolong the clinical outcome of POI, while future therapies should be aimed at enhancing MΦ physiological repair functions.
Crucial Role of Complement Activation and IL-1β in Bone Marrow Niche of Immune Thrombocytopenia
Authors: Xiao-Lu Zhu, Jia-Min Zhang, Qian-Ming Wang, Hai-Xia Fu, Meng Lv, Yuan Kong, Ying-Jun Chang, Lan-Ping Xu, Kai-Yan Liu, Xiao-Jun Huang, Xiao-Hui Zhang
Journal: Blood (2016)