tbuckley/cabot-search huggingface dataset:
Abstract 228: Alterations of Cardiac Morphology and Function Caused by Cardio-Thoracic Surgery in Small Animal Models of Heart Disease
Authors: Peter Nordbeck, Leoni Bönhof, Karl-Heinz Hiller, Sabine Voll, Paula Arias, Lea Seidlmayer, Tatjana Williams, Yu-Xiang Ye, Daniel Gensler, Theo Pelzer, Georg Ertl, Peter M Jakob, Wolfgang R Bauer, Oliver Ritter
Journal: Circulation Research (2013)

Background: Surgical procedures in small animal models of heart disease, such as artificial ligation of the coronary arteries for experimental myocardial infarction, can evoke alterations in cardiac morphology and function. Such alterations might induce artificial early or long term effects in vivo that might account for a significant bias in basic cardiovascular research, and, therefore, could potentially question the meaning of respective studies in small animal models of heart disease. Methods: Female Wistar rats were matched for weight and distributed to sham left coronary artery ligation or untreated control. Cardiac parameters were then investigated in vivo by high-field MRI over time after the surgical procedure, determining left and right ventricular morphology and function. Additionally, the time course of several metabolic and inflammatory blood parameters was determined. Results: Rats after sham surgery showed a lower body weight for up to 8 weeks after the intervention compared to healthy controls. Left and right ventricular morphology and function were not different in absolute measures in both groups 1 week after surgery. However, there was a confined difference in several cardiac parameters normalized to the body weight (bw), such as myocardial mass (2.19±0.30/0.83±0.13 vs. 1.85±0.22/0.70±0.07 mg left/right per g bw, p&lt;0.05), or enddiastolic ventricular volume (1.31±0.36/1.21±0.31 vs. 1.14±0.20/1.07±0.17 µl left/right per g bw, p&lt;0.05). Vice versa, after 8 weeks, cardiac masses, volumes, and output showed a trend for lower values in the sham operated rats compared to the controls in absolute measures (782.2±57.2/260.2±33.2 vs. 805.9±84.8/310.4±48.5 mg, p&lt;0.05 for left/right ventricular mass), but not normalized to body weight. Matching these findings, blood testing revealed prolonged metabolic and inflammatory changes after surgery not related to cardiac disease. Conclusion: There is a small distinct impact of cardio-thoracic surgical procedures on the global integrity of the organism, which in the long term also includes circumscribed repercussions on cardiac morphology and function. This impact has to be considered when analyzing data from respective studies and transferring the findings to conditions in patients.
The many ways of osteoclast activation
Authors: Joseph Lorenzo
Journal: Journal of Clinical Investigation (2017)

Osteoclasts are the cells responsible for bone resorption, a process that is essential for the maintenance of healthy bones. Bone diseases, such as osteoporosis, which are characterized by high rates of bone resorption and loss of bone mass, may benefit from treatments that inhibit osteoclast formation and/or function. The RANKL/RANK pathway is critical for both osteoclast formation and function, and these effects are thought to be mediated by the transcription factor nuclear factor of activated T cells, cytoplasmic 1 (NFATc1). In this issue of the JCI, Bae et al. challenge the convention that NFATc1 is the sole critical regulator of RANKL/RANK-dependent osteoclast activation. Specifically, the authors show that MYC drives metabolic reprogramming in osteoclasts and that MYC induces estrogen receptor-related receptor α (ERRα) to regulate osteoclastogenesis. Importantly, both loss of MYC and pharmacological inhibition of ERRα attenuated bone loss in a mouse model of osteoporosis. Together, the results of this study suggest that the MYC/ERRα pathway should be further explored as a drug target for bone diseases.
Quality of life: An independent prognostic variable in a general population of cancer patients receiving chemotherapy
Authors: J. F. Grutsch, D. Gupta, J. Granick, T. Wodek, C. G. Lis
Journal: Journal of Clinical Oncology (2007)

19596 Background: It is uncertain whether the current Quality of Life (QL) instruments can facilitate clinical decision-making in oncology. Since the most important outcome in oncology is survival, we investigated QL domains from 2 contrasting QL instruments, EORTC QLQ-C30 and the Quality of Life Index (QLI) to determine if these instruments can partition a heterogeneous population of cancer patients into distinct prognostic groupings. Methods: 1,200 patients consented to participate in Cancer Treatment Center of America's QL program between Mar ‘01 and May ’05. We identified 494 deaths in this group. Most common tumors were breast (n=319), colon (n=159), and lung (n=209). Among 434 patients undergoing definitive treatment 159 had stage 4 and 49 had stage 3 disease, the other patients had failed definitive therapy. The median survival was 39 weeks for newly diagnosed patients and 29.9 weeks for patients with recurrent disease. We used cutpoint analysis using statistical strength of association with QL scores to determine the association between QL score and survival. This information was then used in a recursive partitioning analysis to group our cancer patient population into mutually exclusive prognostic groups. Results: We found several QL domains had a non-linear relationship with survival, which indicates that a relatively small change in QL score could result in a large change in survival. QLI Health/Functioning domain, had the strongest association with survival. Subsequent iterations of the recursive partitioning found that a combination of clinical and QL domain scores partitioned the patient population into distinct groups, whose median survival ranged from 13–100 weeks. Patients with the best prognosis had high QLI health satisfaction scores health and had hormonally dependent tumors. The patients with the poorest survival had intermediate QLI health satisfaction scores, poor appetite, and poor emotional function. Conclusion: This retrospective analysis found specific combination of QL domains and scores that partitioned patients with advanced cancer into distinct prognostic groupings. This analysis indicates that our current instruments have the potential to be developed into tools that could facilitate clinical decision-making. No significant financial relationships to disclose.
Tumor Markers in Diagnosis and Follow up of Haematologic Malignancies
Authors: Zisis Kontoninas, Georgia D Kaiafa, Zoi Saouli, Christos G Savopoulos, Didangelos Triantafyllos, Achilles Anagnostopoulos, Apostolos I Hatzitolios, Athanasios Papadopoulos
Journal: Blood (2016)
Histone methyltransferase G9a promotes liver cancer development by epigenetic silencing of tumor suppressor gene RARRES3
Authors: Lai Wei, David Kung-Chun Chiu, Felice Ho-Ching Tsang, Cheuk-Ting Law, Carol Lai-Hung Cheng, Sandy Leung-Kuen Au, Joyce Man-Fong Lee, Carmen Chak-Lui Wong, Irene Oi-Lin Ng, Chun-Ming Wong
Journal: Journal of Hepatology (2017)
The Suppressor-Cell Network in Cancer
Authors: Samuel Broder, Thomas A. Waldmann
Journal: New England Journal of Medicine (1978)

Suppressor Cells in the Enhancement of Tumor GrowthOncogenesis is accompanied by the appearance of tumor-associated cellular neoantigens in a large number of carefully studied models. The immuno-competent cells of the host can frequently recognize these antigens as "non-self" surface antigens and, under some conditions, can inhibit tumor progression. However, in many instances the tumor grows in spite of its "non-self" antigens and an apparent host immune response. For a number of years, the ineffectual immune response of tumor-bearing hosts was ascribed to the presence of circulating-blocking factors thought to impede the neutralization of tumor cells . . .
Effects of Food on Drug Absorption
Authors: P G Welling
Journal: Annual Review of Nutrition (1996)

This chapter provides an update on drug-food interactions reported in the literature during the past five years. The number of studies examining this phenomenon has increased dramatically, and many of the results of these studies have been unpredictable and spectacular. Drug-food interactions should really be considered as formulation-food interactions because of increasing evidence that a drug may be affected differently by food when it is administered in different formulations. Drug-food interactions may be classified into five categories: those causing reduced, delayed, increased, and accelerated absorption, and those in which food has no effect. While it continues to be necessary to examine drugfood interactions for specific drugs and drug formulations, additional avenues need to be explored to seek mechanistic patterns that may lead to better prediction of the nature and extent of changes in circulating drug levels due to the presense of food, and their possible clinical impact.
The transcriptional coactivator TAZ regulates reciprocal differentiation of TH17 cells and Treg cells
Authors: Jing Geng, Shujuan Yu, Hao Zhao, Xiufeng Sun, Xun Li, Ping Wang, Xiaolin Xiong, Lixin Hong, Changchuan Xie, Jiahui Gao, Yiran Shi, Jiaqi Peng, Randy L Johnson, Nengming Xiao, Linrong Lu, Jiahuai Han, Dawang Zhou, Lanfen Chen
Journal: Nature Immunology (2017)
Segmentation of lumen and outer wall of abdominal aortic aneurysms from 3D black-blood MRI with a registration based geodesic active contour model
Authors: Yan Wang, Florent Seguro, Evan Kao, Yue Zhang, Farshid Faraji, Chengcheng Zhu, Henrik Haraldsson, Michael Hope, David Saloner, Jing Liu
Journal: Medical Image Analysis (2017)
Conservative management of young women with endometrial adenocarcinoma with grade 2-3 and/or superficial myometrial invasion.
Authors: Jeong-Yeol Park, Dae-Yeon Kim, Tae-Jin Kim, Jae Weon Kim, Jong-Hyeok Kim, Yong-Man Kim, Young-Tak Kim, Duk-Soo Bae, Joo-Hyun Nam
Journal: Journal of Clinical Oncology (2013)

5601 Background: To estimate the oncologic and pregnancy outcomes after progestin treatment of young women with endometrial adenocarcinoma with grade 2–3 and/or superficial myometrial invasion. Methods: Medical records of 48 young women with endometrioid adenocarcinoma of the uterus with grade 2–3 and/or superficial myometrial invasion who were conservatively managed with oral progestin were reviewed. Results: Fourteen patients (29.2%) received daily oral megestrol acetate (median dose, 160 mg/day; range, 40–240 mg/day) and 34 (70.8%) received daily oral medroxyprogesterone acetate (median dose, 500 mg/day; range, 80–1000 mg/day). The median treatment duration was 10 months (range, 3–20 months). Complete responses were observed in 37 patients (77.1%) and the median time to complete response was 17 weeks (range, 9–51 weeks). Complete response rates were 76.5%, 73.9%, and 87.5% for patients with grade 2–3 without myometrial invasion (n=17), patients with grade 1 and superficial myometrial invasion (n=23), and patients with grade 2-3 and superficial myometrial invasion (n=8), respectively (P = 0.731). Their recurrence rates after a median follow-up time of 48 months (range, 7–136 months) were 23.1%, 47.1%, and 71.4%, respectively (P = 0.104). None experienced disease progression or died of the disease. Nine patients gave birth to 10 healthy babies. Conclusions: Progestin treatment is safe for patients with grade 2–3 without myometrial invasion and patients with grade 1 and superficial myometrial invasion. However, it should be provided on an individual basis and must be applied cautiously in patients with grade 2–3 and superficial myometrial invasion.
Late Anthracycline-Related Cardiotoxicity in Low-Risk Breast Cancer Patients
Authors: Viviana Maestrini, Mun H. Cheang, Paul Kotwinski, Stefania Rosmini, Guy Lloyd, Peter Kellman, Dudley J. Pennell, Hugh Montgomery, James C. Moon, Charlotte Manisty
Journal: Journal of the American College of Cardiology (2017)
Implicit attitudes, eating behavior, and the development of obesity
Authors: Jasmine M DeJesus
Journal: Behavioral and Brain Sciences (2017)

Abstract Nettle et al. describe increasing food intake (relative to energy expenditure) in response to food insecurity as a key contributor to obesity. I argue that a variety of implicit psychological mechanisms underlie this process to contribute to weight gain. The biobehavioral pathways and the social nature of food selection discussed here are importantly related to food selection and obesity.
PWE-111 Higher Red Blood Cell Methotrexate Polyglutamates Correlate With Increased Disease Activity, And Are Useful In Assessing Adherence: Abstract PWE-111 Table 1
Authors: S Fong, MG Ward, I Nasr, RM Goel, KV Patel, S Ray, M Arenas Hernandez, SA Anderson, T Marinaki, JD Sanderson, PM Irving
Journal: Gut (2014)

<h3>Introduction</h3> Methotrexate (MTX) is commonly used in patients with inflammatory bowel disease (IBD). Within red blood cells (RBC), MTX is activated by sequential addition of glutamic acid residues to form polyglutamates (MTXPG <sub>1–5</sub>). In rheumatoid arthritis, low [MTXPG] has been associated with active disease, whereas other studies have demonstrated an inverse relationship, including the only published data in IBD. The aim of this study was to determine if RBC [MTXPG] reflect clinical response in IBD patients and whether they are useful in assessing adherence. <h3>Methods</h3> This was a single-centre, retrospective pilot study of 21 IBD patients treated with weekly MTX. RBC MTXPG<sub>1–5</sub> was measured using high-performance liquid chromatography. Clinical status (active disease or remission) was assessed by 2 IBD physicians blinded to [MTXPG], using a combination of prospectively recorded clinical activity indices (Simple Colitis Activity Index, Harvey Bradshaw Index), endoscopy, faecal calprotectin and C reactive protein (CRP). Pearson correlation coefficient, r was calculated to assess the relationship between MTX dose and [MTXPG]. Association between [MTXPG] and clinical response was analysed with unpaired t-test. <h3>Results</h3> 4/21(22%) patients (3 of whom admitted non-adherence) had undetectable MTXPGs and were excluded from further analysis. MTXPG<sub>2–4</sub> were detected in all adherent patients. PG<sub>3</sub> was the predominant polyglutamate accounting for a mean of 43% of total MTXPG. A linear relationship between dose of MTX and PG<sub>1–5</sub> was observed. 12/21(57%) patients were assessed as having active disease. No significant difference in mean [MTXPG<sub>n</sub>] was observed between those with active disease and remission. For each MTXPG<sub>n</sub>, a non-significant trend towards a higher concentration was observed in patients with active disease. <h3>Conclusion</h3> In this study, the largest to date in IBD, measuring RBC MTXPG was useful in assessing adherence to MTX. A trend towards higher PG concentrations was associated with active disease confirming the findings in the only other study in IBD. Whether this is confounded by higher doses being used in patients with more active disease warrants further study in larger, prospective trials. <h3>Reference</h3> <h3>Disclosure of Interest</h3> None Declared.
Does faster rituximab infusion for patients with NHL lower cancer care costs?
Authors: Carolina Reyes, Minghan Dai, Hans-Peter Goertz, Keith L Dawson, John C. Hornberger
Journal: Journal of Clinical Oncology (2013)

e17561 Background: Rituximab in combination with chemotherapy is recommended for non-Hodgkin’s lymphoma. A faster (90-minute) infusion schedule for rituximab has been found to be safe and feasible in NHL patients who tolerate their first infusion administered at the standard rate (Phase III study RATE trial; NCT00719472). This study’s objective was to assess the economic impact of adopting the 90-minute rituximab infusion from a US societal perspective. Methods: The analysis complied with the jointly published Good Research Practice guidelines of the International Society of Pharmacoeconomic and Outcome Research and the Society of Medical Decision Making. The target population was US patients in 2013 with previously untreated diffuse large B-cell lymphoma (DLBCL) or follicular lymphoma (FL) who were scheduled to receive rituximab plus CHOP or CVP. Costs included direct medical costs (drug and administration cost, pre-medication cost, cost of adverse events) and indirect costs (income foregone by patients and informal caregivers due to visit duration for infusion). Data sources included RATE trial, Medicare Fee Schedules, and US Labor Department statistics. Results: Of the 23,519 newly diagnosed DLBCL and FL patients in the target population, the estimated direct medical costs and foregone (patient and caregiver) income for conventional infusion totaled $825,005,088 and $9,293,180 respectively. The 90-minute infusion reduced direct medical costs by $2,205,689 (0.3%) and foregone patient income by $3,628,185 (39%). The average cost savings for each patient was $42 per infusion and $248 per course. The factors that most influenced savings included cost to treat adverse events, administration costs, and patient wage rates. As a result from a shorter infusion duration, the increased center capacity may lead to a larger saving as the fixed center costs can be distributed across more patients. Conclusions: In the context of tremendous focus on affordably improving population health, this study confirms that compared with conventional rituximab infusion regimen, a novel, validated regimen that is 3-4 fold faster to administer and is as safe results in direct medical savings and reduces productivity loss for patients and caregivers.
为什么医生使用无效的治疗措施？——有许多原因——包括医生不能“什么都不做”
Authors: 李晓惠, 杜军保
Journal: BMJ (2004)

James Lind的著名试验——柑桔类水果可以治疗坏血病的其中一个惊人之处是，他不仅忽略了自己的试验证据，而且在临床实践中继续倡导那些他已经发现无效的治疗，包括应用含硫酸的物质。医学史上充满了曾经是临床通用但现在被证明是无效甚至是对患者有害的治疗先例：由于法国的外科医生Pare恰好
Dissociative Disorders in DSM-5
Authors: David Spiegel, Roberto Lewis-Fernández, Ruth Lanius, Eric Vermetten, Daphne Simeon, Matthew Friedman
Journal: Annual Review of Clinical Psychology (2013)

The rationale, research literature, and proposed changes to the dissociative disorders and conversion disorder in the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) are presented. Dissociative identity disorder will include reference to possession as well as identity fragmentation, to make the disorder more applicable to culturally diverse situations. Dissociative amnesia will include dissociative fugue as a subtype, since fugue is a rare disorder that always involves amnesia but does not always include confused wandering or loss of personality identity. Depersonalization disorder will include derealization as well, since the two often co-occur. A dissociative subtype of posttraumatic stress disorder (PTSD), defined by the presence of depersonalization or derealization in addition to other PTSD symptoms, is being recommended, based upon new epidemiological and neuroimaging evidence linking it to an early life history of adversity and a combination of frontal activation and limbic inhibition. Conversion disorder (functional neurological symptom disorder) will likely remain with the somatic symptom disorders, despite considerable dissociative comorbidity.
EGFR Mutation Analysis for Prospective Patient Selection in Two Phase II Registration Studies of Osimertinib
Authors: Suzanne Jenkins, James Chih-Hsin Yang, Pasi A. Jänne, Kenneth S. Thress, Karen Yu, Rachel Hodge, Susie Weston, Simon Dearden, Sabina Patel, Mireille Cantarini, Frances A. Shepherd
Journal: Journal of Thoracic Oncology (2017)
Ipilimumab for Advanced Melanoma in an Expanded Access Programme (EAP): Ocular, Mucosal and Acral Subtype UK Experience
Authors: H. Shaw, J. Larkin, P. Corrie, S. Ellis, J. Nobes, E. Marshall, S. Kumar, S. Danson, R. Plummer, P. Nathan
Journal: Annals of Oncology (2012)
Abstract 256: Dysfunctional Cardiac Stem Cell Niches Condition the Aging of the Heart
Authors: Fumihiro Sanada, Hanqiao Zheng, Donato Cappetta, Emily Mangano, Junghyun Kim, Christian Arranto, Noriko Ide-Iwata, Ada Pesapane, Mario Ricciardi, Narasimman Gurusamy, Polina Goichberg, Marcello Rota, Toru Hosoda, Jan Kajstura, Piero Anversa, Annarosa Leri
Journal: Circulation Research (2012)

The objective of this study was to determine whether aging of the heart is characterized by alterations in the cellular composition of cardiac niches and defective cardiomyogenesis. By employing a morphometric approach in which the three-dimensional structure of each niche was evaluated, we examined 40 and 20 cardiac niches in young and old Fischer 344 rats, respectively. Although a niche can include a single stem cell, clusters composed of three or more cardiac stem cells (CSCs) and early lineage committed cells (LCCs) were included in the analysis. LCCs expressed the stem cell antigen c-kit in combination with the marker of cardiac commitment GATA4. The average volume of the niches did not vary with age. Surprisingly, the number of lineage-negative CSCs increased from 4 to 28 months. Young niches contained 6 CSCs while old niches showed 10 CSCs. However, the fraction of CSCs positive for the senescence-associated marker p16 INK4a increased 14-fold with age, from 6% to 85%. Corresponding values for LCCs were 8% and 82%. Apoptosis of CSCs-LCCs increased with age and was restricted to p16 INK4a -positive-cells. However, the fraction of senescent CSCs-LCCs undergoing apoptosis decreased 3.5-fold with age: apoptosis was detected in 7% and 2% of p16 INK4a positive CSCs-LCCs of young and old animals, respectively resulting in the accumulation of senescent cells.Freshly isolated CSCs proliferated in response to growth stimuli but this effect was attenuated in old cells. This finding was consistent with the decreased expression of the insulin-like growth factor receptor 1 (IGF-1R) in senescent CSCs. Collectively, the accumulation of senescent CSCs and the poor response of p16 INK4a- negative CSCs to growth stimuli determined the formation of dysfunctional niches. Abnormal niche turnover led to the generation of rapidly aging cardiomyocytes. In conclusion, the cellular composition of the niches varies with age. The decrease in the number of functionally-competent CSCs-LCCs together with the accumulation of senescent CSCs-LCCs limits the ability of CSC niches to repopulate the senescent ventricular myocardium.
Continuous epidural ropivacaine infusion reduces intra-abdominal pressure, postoperative pain and normalizes lungs' mechanical changes in critically ill children after major abdominal operation
Authors: Dmytro Dmytriiev, Olexander Mazulov, Nataliia Kosechenko
Journal: European Respiratory Journal (2013)

Background: We aimed to study the influence of prolonged infusion of ropivacaine on postoperative pain, intra-abdominal pressure (IAP) and mechanical lungs9 changes that may happen in children.  Methods: First group (14 patients) we used for analgesia morphine hydrochloride (0,1 mg/kg), second (10 patients) - infusion of continuous epidural ropivacaine 0,2%. Interdependency of lungs9 mechanical characteristics with effectiveness of post-operative analgesia and abdominal wall relaxation was studied in the way of continuous monitoring of dynamic compliance (Cdyn), pressure-volume and flow-volume loops. We measured blood level of cortisol, analyzed subjectively postoperative pain syndrome using visual analogue scales (VAS). IAP was controlled by Cron. For statistic analysis we used Student9s t-test.  Results: In the first group the increase of IAP (14,4±1,2 vs 5,2±0,6 cm H2O, second group). Levels of pain according to VAS were variable in first group, increase of cortisol levels in first group (670,3 ± 34,4 nmol/l, vs 230,4 ± 20,2 nmol/l, second group). Periods with high traumatic effects and poor analgesia (morphine group) reasoned the increase of IAP, Cdyn decreasing in 3,4 times, resistance in 2,2 times and PIP rising till 22,1± 1,4 cm H2O and maximum changes in graphic monitor.  Conclusions: To provide adequate analgesia in peri-operative period is better to give prolongation epidural infusion of ropivacaine, because it results in stability of IAP, prevents pain, decreases intra-abdominal hypertensive mechanisms, gives the possibility to lungs function in physiological conditions.