tbuckley/cabot-search huggingface dataset:
Response to: ‘Disease activity and left ventricular systolic function in rheumatoid arthritis’ by Giollo<i>et al</i>
Authors: Helga Midtbø, Anne Grete Semb, Knut Matre, Tore K Kvien, Eva Gerdts
Journal: Annals of the Rheumatic Diseases (2016)

We thank Giollo et al 1 for their interest and comments to our paper.2 In this paper, we demonstrated that rheumatoid arthritis (RA) disease activity was associated with lower left ventricular (LV) myocardial systolic function when assessed by stress-corrected midwall shortening (scMWS) or global longitudinal strain (GLS).2 Further, we found that this association was independent of the presence of a normal ejection fraction and traditional cardiovascular risk factors like hypertension and smoking. In a letter to the editor, Giollo et al 1 present data from a series of 235 patients with RA.3 …
ATP Production Rate via Creatine Kinase or ATP Synthase In Vivo
Authors: Qiang Xiong, Fei Du, Xiaohong Zhu, Pengyuan Zhang, Piradeep Suntharalingam, Joseph Ippolito, Forum D. Kamdar, Wei Chen, Jianyi Zhang
Journal: Circulation Research (2011)

³¹P magnetization saturation transfer (MST) experiment is the most widely used method to study ATP metabolism kinetics. However, its lengthy data acquisition time greatly limits the wide biomedical applications in vivo, especially for studies requiring high spatial and temporal resolutions.We aimed to develop a novel superfast MST method that can accurately quantify ATP production rate constants (k(f)) through creatine kinase (CK) or ATP synthase (ATPase) with 2 spectra.The T₁(nom) (T₁ nominal) method uses a correction factor to compensate the partially relaxed MST experiments, thus allowing measurement of enzyme kinetics with an arbitrary repetition time and flip angle, which consequently reduces the data acquisition time of a transmurally differentiated CK k(f) measurement by 91% as compared with the conventional method with spatial localization. The novel T₁(nom) method is validated theoretically with numeric simulation, and further verified with in vivo swine hearts, as well as CK and ATPase activities in rat brain at 9.4 Tesla. Importantly, the in vivo data from swine hearts demonstrate, for the first time, that within an observation window of 30 minutes, the inhibition of CK activity by iodoacetamide does not limit left ventricular chamber contractile function.A novel MST method for superfast examination of enzyme kinetics in vivo has been developed and verified theoretically and experimentally. In the in vivo normal heart, redundant multiple supporting systems of myocardial ATP production, transportation, and utilization exist, such that inhibition of one mechanism does not impair the normal left ventricular contractile performance.
Effect of dose intensity and overexpression of topoisomerase iia on survival in patients with locally advanced breast cancer treated with anthracyclines
Authors: T. Vidaurre, M. Olivera, H. Gómez, J. Pinto, F. Doimi, R. Velarde, J. Abugattas, J. Leon, L. Mas, C. Vigil
Journal: Journal of Clinical Oncology (2008)

11512 Background: TopoIIa is a therapeutic target of anthracyclins, its predictive and prognostic value in breast cancer is being evaluated. The aim of this study was to determine the effect of anthracycline dose intensity in terms of overall(OS) and free disease survival (DFS) in patients with over expressing TopoIIa. Methods: TopoIIa expression in locally advanced breast cancer samples that receive neoadjuvant treatment with doxorubicin were evaluated. Expression of TopoIIa was determined by immunohistochemistry in samples embedded in paraffin. Patients expressing TopoIIa were clustered according to the dose intensity of doxorubicin (≤ 24 or > 24 mg/m2/week). Survival curves were determined by Kaplan-Meier test and the comparations with the Logrank test. Results: 109 samples were evaluated. 40/109 (36.7%) over express TopoIIa, there was no differences in clinical characteristics in both groups. In patients TopoIIa positive, the median to age was 47 years (range: 33–74), Postmenopausal 30/40 (75%), ductal carcinoma 37/40 (92.5%) and lobulillar carcinoma 3/40 (7.5%). Positive estrogen receptors: 18/40 (45%) and positive progesterone receptor: 11/40 (27.5%). High proliferation index of expression of Ki-67 (≥40%) in 21/35 (40%) and HER2 positive in 10/37 (27%). Dose intensity of doxorubicin: ≤ 24 mg/m2/week in 15/40 (37.5%) and > 24 mg/m2/week in 25/40 (62.5%). Results of efficacy are showed in the follow table: Conclusions: Patients with locally advanced breast cancer and over expression of TopoIIa receiving a dose intensity > 24 mg/m2/week present a better survival than patients receiving lower dose intensities. Total < 24 mg/m2/week > 24 mg/m2/week p DFS Median 30 months 16 months 63 months 0.010 5 years OS 38% 13% 50% Median 32 months 27 months 57 months 0.027 5 years 35 % 14 % 45 % No significant financial relationships to disclose.
Effectiveness of Intrathecal Liposomal Cytarabine in Treatment of Childhood Hematopoietic Malignancies – Experience of Polish Pediatric Leukemia/Lymphoma Study Group
Authors: Tomasz Szczepanski, Lidia Kajdas, Aneta Pobudejska-Pieniazek, Ninela Irga, Maciej Niedzwiecki, Katarzyna Derwich, Jacek Wachowiak, Grazyna Sobol, Malgorzata Krupa, Jolanta Stefaniak, Wojciech Mlynarski, Ewa Niedzielska, Bernarda Kazanowska, Izabela Palgan, Andrzej Kurylak, Maria Wieczorek, Tomasz Urasinski, Jerzy R Kowalczyk
Journal: Blood (2011)
Metabolite and Microbiome Interplay in Cancer Immunotherapy
Authors: Caroline H. Johnson, Mary E. Spilker, Laura Goetz, Scott N. Peterson, Gary Siuzdak
Journal: Cancer Research (2016)

Abstract The role of the host microbiome has come to the forefront as a potential modulator of cancer metabolism and could be a future target for precision medicine. A recent study revealed that in colon cancer, bacteria form polysaccharide matrices called biofilms at a high frequency in the proximal colon. Comprehensive untargeted and stable isotope–assisted metabolomic analysis revealed that the bacteria utilize polyamine metabolites produced from colon adenomas/carcinomas to build these protective biofilms and may contribute to inflammation and proliferation observed in colon cancer. This study highlighted the importance of finding the biological origin of a metabolite and assessing its metabolism and mechanism of action. This led to a better understanding of host and microbial interactions, thereby aiding therapeutic design for cancer. In this review, we will discuss methodologies for identifying the biological origin and roles of metabolites in cancer progression and discuss the interactions of the microbiome and metabolites in immunity and cancer treatment, focusing on the flourishing field of cancer immunotherapy. Cancer Res; 76(21); 6146–52. ©2016 AACR.
Adrenocortical Cancer: A Molecularly Complex Disease Where Surgery Matters
Authors: Eden C. Payabyab, Sanjeeve Balasubramaniam, Maureen Edgerly, Margarita Velarde, Maria J. Merino, Aradhana M. Venkatesan, Harshraj Leuva, Thomas Litman, Susan E. Bates, Tito Fojo
Journal: Clinical Cancer Research (2016)

The development of new therapies has lagged behind for rare cancers without defined therapeutic targets. Adrenocortical cancer is no exception. Mitotane, an older agent considered "adrenolytic," is used both to control symptoms in advanced disease and as adjuvant therapy after surgical resection. Molecular characterization of adrenocortical cancer has deepened our understanding of this genetically complex disease while identifying subgroups whose importance remains to be determined. Unfortunately, such studies have yet to demonstrate a therapeutic target for drug development, and to date, no targeted therapy has achieved meaningful outcomes. Consequently, first-line therapy for metastatic disease remains a combination regimen of etoposide, doxorubicin, and cisplatinum established in a randomized clinical trial. In addition to evaluating recent studies in adrenocortical cancer, we raise one critical clinical issue-the risk of peritoneal dissemination following laparoscopic resection of adrenocortical cancer. In a retrospective case series of 267 patients referred to the NCI for the treatment of recurrent or advanced adrenocortical cancer, we found extensive peritoneal dissemination in 25 of the 45 patients (55.6%) who had undergone laparoscopic resection, compared with only 7 of the 222 patients (3%) who had undergone an open resection (P < 0.0001). Although this has been debated in the literature, our data argue for an end to laparoscopic resection of adrenocortical cancers to avoid peritoneal dissemination, a complication of laparoscopy that is uniformly fatal. Clin Cancer Res; 22(20); 4989-5000. ©2016 AACR SEE ALL ARTICLES IN THIS CCR FOCUS SECTION, "ENDOCRINE CANCERS REVISING PARADIGMS".
Immunohistochemical analysis of T-type calcium channels in acquired melanocytic naevi and melanoma
Authors: O. Maiques, A. Macià, S. Moreno, C. Barceló, M. Santacana, A. Vea, J. Herreros, S. Gatius, E. Ortega, J. Valls, B.J. Chen, D. Llobet-Navas, X. Matias-Guiu, C. Cantí, R.M. Marti
Journal: British Journal of Dermatology (2016)

Cutaneous malignant melanoma arises from transformed melanocytes de novo or from congenital or acquired melanocytic naevi. We have recently reported that T-type Ca2+ channels (TT-Cs) are upregulated in human melanoma and play an important role in cell proliferation.To describe for the first time in formalin-fixed paraffin-embedded tissue the immunoexpression of TT-Cs in biopsies of normal skin, acquired melanocytic naevi and melanoma, in order to evaluate their role in melanomagenesis and/or tumour progression, their utility as prognostic markers and their possible use in targeted therapies.Tissue samples from normal skin, melanocytic naevi and melanoma were subjected to immunohistochemistry for two TT-Cs (Cav3.1, Cav3.2); markers of proliferation (Ki67), the cell cycle (cyclin D1), hypoxia (Glut1), vascularization (CD31) and autophagy (LC3); BRAF V600E mutation (VE1) and phosphatase and tensin homologue (PTEN). Immunostaining was evaluated by histoscore. In silico analysis was used to assess the prognostic value of TT-C overexpression.TT-C immunoexpression increased gradually from normal skin to common naevi, dysplastic naevi and melanoma samples, but with differences in the distribution of both isoforms. Particularly, Cav3.2 expression was significantly higher in metastatic melanoma than in primary melanoma. Statistical correlation showed a linear interaction between PTEN loss/BRAF V600E/Cav3.1/LC3/ Ki67/cyclin D1/Cav3.2/Glut1. Disease-free survival (DFS) and overall survival correlated inversely with overexpression of Cav3.2. DFS also correlated inversely with overexpression of Cav3.1.TT-C immunoexpression on melanocytic neoplasms is consistent with our previous in vitro studies and appears to be related to tumour progression. TT-C upregulation can be considered as a prognostic marker using The Cancer Genome Atlas database. The high expression of Cav3.2 in metastatic melanoma encourages the investigation of the use of TT-C blockers in targeted therapies.
Feasibility of Implementing Minimal Residual Disease Monitoring in Acute Promyelocytic Leukemia Patients Treated in Developing Countries
Authors: Ana Paula Alencar de Lima Lange, Ana Sílvia Gouvea Lima, Rafael Jacomo, Raul A Melo, Rosane Bittencourt, Ricardo Pasquini, Katia B. Pagnano, Evandro M. Fagundes, Maria de Lourdes Chauffaille, Carlos S Chiattone, Francesco LoCoco, David Grimwade, Eduardo M. Rego
Journal: Blood (2014)
Counting the cost of an outbreak of carbapenemase-producing Enterobacteriaceae : an economic evaluation from a hospital perspective
Authors: J.A. Otter, P. Burgess, F. Davies, S. Mookerjee, J. Singleton, M. Gilchrist, D. Parsons, E.T. Brannigan, J. Robotham, A.H. Holmes
Journal: Clinical Microbiology and Infection (2016)
Optimizing breast cancer diagnosis in Kenya: Importance of standardization of technical methodologies for comparative breast cancer data.
Authors: Shahin Sayed, Zahir Moloo, Ronald Wasike, Rajendra R. Chauhan, Sudhir Vinayak, Joseph Karanu, Peter Bird, Wambui Njoroge, Ancent Nzioka, Andrew Gachii, David Chumba, James Obondi Otieno, Musa Mohamed, Ammar Al-Ammary, Omar Sherman, Satya Prasad, Catherine Kyobutungi, Mansoor N. Saleh
Journal: Journal of Clinical Oncology (2012)

139 Background: An analysis of 322 cases referred to Aga Khan University, Nairobi, revealed 56% estrogen receptor (ER) positive tumors and 35% prevalence of triple-negative breast cancer (TNBC). Findings were retrospective and limited by inability to control pre-analytical variables that could potentially impact results. Methods: As part of an ongoing prospective study assessing prevalence of TNBC in the three major ethnic groups in Kenya, we gathered a multidisciplinary team from 10 collaborating health facilities around Kenya for an educational workshop. The objectives were to assess baseline capabilities and pre-analytic variables at each center, identify gaps and provide hands-on training in order to ensure accuracy and validity of ER/PR/HER2 prevalence data gathered as part of the study. Results: See table. Breast cancer biopsies ranged from one to 20 per month per center. Diagnosis was predominantly by FNA and ER/PR/HER2 was not routinely performed. Buffered formalin fixative and standardized CAP reporting format was employed only at one center. A survey 3 months following the workshop demonstrated increase in diagnostic core biopsiesby 90%, and uniform use of buffered formalin fixative, and adoption of synoptic reporting. 66 prospective cases of breast cancer from the 10 institutions with patients from different ethnic backgrounds have been subsequently collected and IHC data will be presented. Conclusions: Much has been made of the difference in prevalence of TNBC in Africa as compared to North America, yet little attention has been paid to differences in diagnostic methodologies and basic tissue handling techniques that can potentially alter results. Despite limitations of resources, educational workshops make it possible to improve the practice of breast cancer diagnosis, and thereby enable accurate comparative analysis between breast cancers in the developing and the developed world. [Table: see text]
Efficacy of preemptive betablockers for prevention of cardiotoxicity in patients undergoing hematopoietic stem cell transplantation.
Authors: Ana CDAH de Souza, Joyce Njoroge, Sadeer Al-Kindi, Marwan Qattan, Brian D Hoit, Ann Liner, Jamie Wilson, Basem M. William, Marcos J.G. De Lima, Guiherme Oliveira
Journal: Journal of Clinical Oncology (2015)

e18012 Background: Little is known about cardiotoxicity in patients receiving hematopoietic stem cell transplantation (SCT) for hematological malignancies. We sought to investigate whether preemptive treatment reduces cardiotoxicity in this cohort. Methods: We prospectively enrolled 39 consecutive adult patients undergoing hematopoietic stem cell transplant for hematological malignancies (September 2013- October 2014). Patients were assessed using a pre-transplant 2D echocardiogram with global longitudinal strain (GLS). Patients were assigned to preemptive treatments; betablocker (BB) and/or angiotensin converting enzyme inhibitors/angiotensin receptor blockers (ACE/ARB), or no intervention (control). GLS was measured after a median of 70 days post-transplant and was compared between groups. Results: Of the 39 enrolled patients, 20 (51.3%) were male with a median age of 57 years (range 24-72). Acute myeloid leukemia (AML) was the most common malignancy in 11 (28.2%) patients. Majority of patients (66.7%) had allogenic SCT. A total of 26 (66.7%) received preemptive treatment (10 BB, 3 ACE/ARB, and 13 BB+ACE/ARB). Eight patients (20.5%) had > 15% decrease in GLS and 3 (7.5%) had > 10% decrease in LVEF. Preemptive BB use was associated with lower risk for GLS decrease (OR 0.159, 95% CI 0.027-0.931, p = 0.041), while ACE/ARB was not associated with lower risk (p = 0.564). GLS increased in the BB group and decreased in the control group (+10.1% vs -5.7%, p = 0.045), but was not different in patients who received ACE/ARB (p = 0.423). LVEF decreased in 1 (4.3%) patient in BB group vs 2 (12.5%) patients in control (p = 0.557). Number needed to treat (NT) with BB was 3.5 to prevent significant drop in GLS. Conclusions: Subclinical cardiotoxicity develops in about a fifth of patients after SCT. Beta blockers may reduce the risk of cardiotoxicity by 84%, with NNT of 3.5. Randomized trials are needed to confirm these findings.
The Potent Deacetylase Inhibitor Trichostatin a (TSA) Increases CXCR4 Expression in Hematopoietic Stem/Progenitor Cells by Chromatin Remodelling
Authors: Hilal Gul, Leah A. Marquez-Curtis, Jennifer Lo, Nadia Jahroudi, A. Robert Turner, Loree M. Larratt, Anna Janowska-Wieczorek
Journal: Blood (2008)
Optimal TBI Dose to Improve the Survival in Unrelated Matched Marrow Transplantation for Adult Patients with Severe Aplastic Anemia: Prospective De-Escalation Study of TBI Dose.
Authors: Jong-Wook Lee, Ki Seong Eom, Yoon Hee Park, Yoo Jin Kim, Seok Lee, Chang Ki Min, Hee Je Kim, Dong Wook Kim, Jong Youl Jin, Woo Sung Min, Chong Won Park, Chun Choo Kim
Journal: Blood (2004)
Those were the days
Authors: L. Farrell
Journal: BMJ (1998)

I wish I'd been a doc in the old west; that was the life. A nice little house with a white picket fence, the respect of the hardworking but hospitable townsfolk, picnics with the buckboard, barn dances, hoedowns, and each fall John Wayne would come riding through and we'd go drinking in the saloons, dancing in the streets, and necking in the parlours.

And occasionally the highlight: the posse, the ultimate male bonding experience. Just picture it; stuck in a boring surgery when the sheriff runs in: “Doc, the bank's been robbed.”

I'd git over there as fast as a horny toad …
A Pathway-focused GSEA Platform In AML That Interrogates Interaction of Flt3ITD and tMLL with Their Epigenetic Targets (p16INK4a, DAPK1, and RUNX3), While Accurately Reporting Broad-based AML Prognosis and Targeting-agent Sensitivity.
Authors: Tareq Al Baghdadi, Chirayu Goswami, Hamid Sayar, Katie J. Sargent, Larry Cripe, Lang Li, Rajasubramaniam Shanmugam, H. Scott Boswell
Journal: Blood (2010)
House dust mite–driven asthma and allergen-specific T cells depend on B cells when the amount of inhaled allergen is limiting
Authors: Melissa Dullaers, Martijn J. Schuijs, Monique Willart, Kaat Fierens, Justine Van Moorleghem, Hamida Hammad, Bart N. Lambrecht
Journal: Journal of Allergy and Clinical Immunology (2016)
Genome-Wide Association of CKD Progression: The Chronic Renal Insufficiency Cohort Study
Authors: Afshin Parsa, Peter A. Kanetsky, Rui Xiao, Jayanta Gupta, Nandita Mitra, Sophie Limou, Dawei Xie, Huichun Xu, Amanda Hyre Anderson, Akinlolu Ojo, John W. Kusek, Claudia M. Lora, L. Lee Hamm, Jiang He, Niina Sandholm, Janina Jeff, Dominic E. Raj, Carsten A. Böger, Erwin Bottinger, Shabnam Salimi, Rulan S. Parekh, Sharon G. Adler, Carl D. Langefeld, Donald W. Bowden, Per-Henrik Groop, Carol Forsblom, Barry I. Freedman, Michael Lipkowitz, Caroline S. Fox, Cheryl A. Winkler, Harold I. Feldman
Journal: Journal of the American Society of Nephrology (2016)

The rate of decline of renal function varies significantly among individuals with CKD. To understand better the contribution of genetics to CKD progression, we performed a genome–wide association study among participants in the Chronic Renal Insufficiency Cohort Study. Our outcome of interest was CKD progression measured as change in eGFR over time among 1331 blacks and 1476 whites with CKD. We stratified all analyses by race and subsequently, diabetes status. Single-nucleotide polymorphisms (SNPs) that surpassed a significance threshold of P &lt;1×10 −6 for association with eGFR slope were selected as candidates for follow-up and secondarily tested for association with proteinuria and time to ESRD. We identified 12 such SNPs among black patients and six such SNPs among white patients. We were able to conduct follow-up analyses of three candidate SNPs in similar (replication) cohorts and eight candidate SNPs in phenotype-related (validation) cohorts. Among blacks without diabetes, rs653747 in LINC00923 replicated in the African American Study of Kidney Disease and Hypertension cohort (discovery P =5.42×10 −7 ; replication P =0.039; combined P =7.42×10 −9 ). This SNP also associated with ESRD (hazard ratio, 2.0 (95% confidence interval, 1.5 to 2.7); P =4.90×10 −6 ). Similarly, rs931891 in LINC00923 associated with eGFR decline ( P =1.44×10 −4 ) in white patients without diabetes. In summary, SNPs in LINC00923 , an RNA gene expressed in the kidney, significantly associated with CKD progression in individuals with nondiabetic CKD. However, the lack of equivalent cohorts hampered replication for most discovery loci. Further replication of our findings in comparable study populations is warranted.
TCT-82 Single versus Dual Anti-Platelet Therapy in Transcatheter Aortic Valve Replacement: a Meta-Analysis of Safety and Efficacy Outcomes
Authors: Rhanderson N. Cardoso, Mohammad M. Ansari, Daniel C. Garcia, Carlos Alfonso, Eduardo de Marchena, Derek Brinster, S Jacob Scheinerman, Giuseppe Martucci, Nicolo Piazza
Journal: Journal of the American College of Cardiology (2015)
Allogeneic Hematopoietic Cell Transplantation for Acute Myelogenous Leukemia in Remission - a Prospective Comparison of Three Different Donor Groups; Matched Sibling, Matched Unrelated, and Haploidentical Family Donors
Authors: Kyoo-Hyung Lee, Je-Hwan Lee, Jung-Hee Lee, Dae-Young Kim, Han-Seung Park, Eun-Ji Choi, Young-Shin Lee, Young-Ah Kang, Mijin Jeon, Miee Seol, Seung-Hyun Baek, Hawk Kim, Jae Hoo Park, Jae-Cheol Jo, Yoon-Sook Choi, Young-Don Joo, Sung-Nam Lim
Journal: Blood (2015)
Author’s reply: The first tick-borne encephalitis case in the Netherlands: reflections and a note of caution
Authors: Vishal Hira, Joris A de Graaf, Barry Rockx
Journal: Eurosurveillance (2016)

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