tbuckley/cabot-search huggingface dataset:
Genetic relatedness analysis reveals the cotransmission of genetically related Plasmodium falciparum parasites in Thiès, Senegal
Authors: Wesley Wong, Allison D. Griggs, Rachel F. Daniels, Stephen F. Schaffner, Daouda Ndiaye, Amy K. Bei, Awa B. Deme, Bronwyn MacInnis, Sarah K. Volkman, Daniel L. Hartl, Daniel E. Neafsey, Dyann F. Wirth
Journal: Genome Medicine (2017)

As public health interventions drive parasite populations to elimination, genetic epidemiology models that incorporate population genomics can be powerful tools for evaluating the effectiveness of continued intervention. However, current genetic epidemiology models may not accurately simulate the population genetic profile of parasite populations, particularly with regard to polygenomic (multi-strain) infections. Current epidemiology models simulate polygenomic infections via superinfection (multiple mosquito bites), despite growing evidence that cotransmission (a single mosquito bite) may contribute to polygenomic infections. Here, we quantified the relatedness of strains within 31 polygenomic infections collected from patients in Thiès, Senegal using a hidden Markov model to measure the proportion of the genome that is inferred to be identical by descent. We found that polygenomic infections can be composed of highly related parasites and that superinfection models drastically underestimate the relatedness of strains within polygenomic infections. Our findings suggest that cotransmission is a major contributor to polygenomic infections in Thiès, Senegal. The incorporation of cotransmission into existing genetic epidemiology models may enhance our ability to characterize and predict changes in population structure associated with reduced transmission intensities and the emergence of important phenotypes like drug resistance that threaten to undermine malaria elimination activities.
Effects of Method of Peripheral Blood Hematopoietic Stem Cell Mobilization (G-CSF, G-CSF + Plerixafor, or Cyclophosphamide + G/GM-CSF) on Engraftment and Sustained Graft Function: Comparison Across Cohorts with Similar CD34+ Cell Dose
Authors: Erin T Alexander, Kathy Hogan, Ashley N Miller, Robert K Stuart, Luciano J Costa
Journal: Blood (2010)
BMET-25RESULTS OF THE INTERIM SAFETY ANALYSIS OF THE DEPOSEIN TRIAL IN LEPTOMENINGEAL METASTASES FROM BREAST CANCER
Authors: Emilie Le Rhun, Fahed Zairi, Thomas Boulanger, Jérôme Barrière, Michel Fabbro, Jennifer Wallet, Jacques Bonneterre, Sophie Taillibert
Journal: Neuro-Oncology (2015)

The Deposein trial (NCT01645839) was designed to evaluate the impact of the intra-CSF liposomal cytarabine on neurological progression free survival (PFS) in breast cancer leptomeningeal metastases (LM). Patients are randomized between systemic treatment alone (arm A) and systemic treatment plus intra-CSF liposomal cytarabine (arm B). The results of the first safety interim analysis on 20 patients (10 per arm) are presented here. At LM diagnosis, median age of patients was 51.5 years in arm A, 56.5 in arm B. Tumors were triple negative in 20% in arm A, 22.2% in arm B and overexpressed HER2 in 80% in arm A, 50% in arm B. Brain metastases were present in 50% in arm A, 10% in arm B. Patients had previously received a median of 2 lines of chemotherapy in arm A, 3 lines in arm B. CSF cytological analysis showed malignant cells in 80% in both arms. MRI LM involvement was observed in 100% in arm A, 80% in arm B. Capecitabine was the most common chemotherapy for LM treatment in both arms (20% in arm A, 30% in arm B). The median number of systemic chemotherapy cycles was 2 (range1-5) in arm A, 6 (range 2-27) in arm B. A median of 6 (range 4-20) liposomal cytarabine injections was administered in arm B. Focal radiotherapy was realized in 10%. Grade 3/4 were observed in 67% of patients of arm A (treatment-related in 22%), and in all patients of arm B (treatment-related in 50% - all due to systemic treatment). The most frequent grade 3/4 complications were neurological disorders (37.5%) in arm A, infections (41%) and haematological disorders (29.5%) in arm B. No chemical meningitis was observed in arm B. These first results need further confirmation. Data on the 42 patients enrolled since the initiation of the study will be presented.
Increased Intracellular Concentration of Reactive Oxygen Species Mediated the Deficient Hematopoiesis of Iron Overload Bone Marrow
Authors: Mingfeng Zhao, Fang Xie, Yuming Li, Juan Mu, Xia Xiao, Haibo Zhu, Xinnv Xu, Qi Deng, Pengjiang Liu, Li Geng, Zonghong Shao
Journal: Blood (2010)
Tipifarnib (Zarnestra, R115777) as Maintenance Therapy for Adults in Complete Remission (CR) Following Induction and Consolidation Therapies for Poor-Risk Acute Myelogenous Leukemia (AML): A Phase II Trial.
Authors: Judith E. Karp, Ivana Gojo, Jacqueline Greer, B. Douglas Smith, Maureen Klein, Jeffery E. Lancet, Steven D. Gore, Lawrence Morris, Alain Thibault, Mary Ellen Rybak, John J. Wright
Journal: Blood (2005)
Donor Lymphocyte Infusion After Allogeneic Hematopoietic Stem Cell Transplantation for Hematological Malignancies.
Authors: Yamin Tan, Lin Cao, Yi Luo, Jimin Shi, Yanlong Zheng, Gaofeng Zheng, Xiaoyan Han, Jie Sun, Xiaoli Zhu, Guoqin Wei, Wenjun Wu, Yanmin Zhao, Huarui Fu, Jingsong He, Li Li, Xiujin Ye, Zhen Cai, Maofang Lin, He Huang
Journal: Blood (2010)
Nilotinib Responses and Tolerability Confirmed in North American Patients with Chronic Myeloid Leukemia (CML) From ENACT (Expanding Nilotinib Access in Clinical Trials).
Authors: Bayard L. Powell, Hanna Jean Khoury, Jeffrey H. Lipton, David A. Rizzieri, Denise Williams, A. Robert Turner
Journal: Blood (2009)
DNA Sequence of the Cancer Genome of a Patient with Therapy-Related Acute Myeloid Leukemia
Authors: Laura Schuettpelz, Daniel C. Link, Dong Shen, Matthew J. Walter, Daniel C Koboldt, David J. Dooling, Robert S. Fulton, Heather Schmidt, Rachel Maupin, Michelle O'Laughlin, Ken Chen, Michael D. McLellan, Shashikant Kulkarni, Jennifer Ivanovich, Michelle Lebeau, Nobish Varghese, Rakesh Nagarajan, Li Ding, Timothy A. Graubert, Timothy J Ley, Richard K. Wilson, Elaine R. Mardis
Journal: Blood (2010)
The validity of the Annual Review of Competence Progression: a qualitative interview study of the perceptions of junior doctors and their trainers
Authors: Rowena Viney, Antonia Rich, Sarah Needleman, Ann Griffin, Katherine Woolf
Journal: Journal of the Royal Society of Medicine (2017)

Objective To investigate trainee doctors' and trainers' perceptions of the validity of the Annual Review of Competence Progression (ARCP) using Messick's conceptualisation of construct validity. Design Qualitative semi-structured focus groups and interviews with trainees and trainers. Setting Postgraduate medical training in London, Kent Surrey and Sussex, Yorkshire and Humber, and Wales in November/December 2015. Part of a larger study about the fairness of postgraduate medical training. Participants Ninety-six trainees and 41 trainers, comprising UK and international medical graduates from Foundation, General Practice, Medicine, Obstetrics and Gynaecology, Psychiatry, Radiology, and Surgery, at all levels of training. Main outcome measures Trainee and trainer perceptions of the validity of the ARCP as an assessment tool. Results Participants recognised the need for assessment, but were generally dissatisfied with ARCPs, especially UK graduate trainees. Participants criticised the perceived tick-box nature of ARCPs as measuring clerical rather than clinical ability, and which they found detrimental to learning. Trainees described being able to populate their e-portfolios with just positive feedback; they also experienced difficulty getting assessments signed off by supervisors. ARCPs were perceived as poor at identifying struggling trainees and/or as discouraging excellence by focussing on minimal competency. Positive experiences of ARCPs arose when trainees could discuss their progress with interested supervisors. Conclusions Trainee and trainer criticisms of ARCPs can be conceptualised as evidence that ARCPs lack validity as an assessment tool. Ongoing reforms to workplace-based assessments could address negative perceptions of the 'tick-box' elements, encourage constructive input from seniors and allow trainees to demonstrate excellence as well as minimal competency, while keeping patients safe.
Biological basis for human capacitation—revisited
Authors: Christopher De Jonge
Journal: Human Reproduction Update (2017)

A little more than a decade ago a review entitled 'Biological basis for human capacitation' was published. A primary conclusion of the review was that with all the technological advances that have been made since the first experiments demonstrated the in vivo requirement of capacitation for fertilization, very little progress had since been made, most significantly for human.The present review was carried out to provide an update on the biological basis for human capacitation. It briefly revisits the original schema, presents a review of the literature that urged research interest in human sperm capacitation and puts under the spotlight the original definition of capacitation balanced against the limitations of experiments in vitro to characterize a complex process that necessarily mandates a female component, and very recent findings in the mouse. It also includes proposed considerations for new thinking regarding capacitation, and progress toward understanding the biology of human capacitation.The PubMed, Google Scholar and Scopus literature databases were reviewed extensively using inclusive, broad and multispecies search terms without publication date limitation.Comprehensive screening of the literature database showed that no papers regarding human sperm capacitation in vivo have been published in the past 20 years. Recent experiments in the mouse have provided compelling and unanticipated data regarding capacitation and in vivo fertilization. Questions were posed and addressed regarding: stimuli for initiation of capacitation, capacitation relative to the cumulus-oocyte complex, comparison between in vivo and in vitro capacitation, and potential species-specific differences in location and timing of capacitation.There has been no progress on the in vivo biology of human sperm capacitation since before the turn of the century. Human IVF and its technologies may likely have inhibited, and continue to hold back, any future in vivo experiments that would address one or more questions regarding acquisition of fertilizing capacity in human. The limiting factor for progress in the area is access to funding and human subjects.
Positron emission tomography for unexplained serum SCC-Ag elevation during follow-up in cervical cancer patients -A phase II study
Authors: T.-C. Chang, T.-C. Yen, J.-H. Hong, C.-H. Lai, K.-K. Ng, S. Hsueh, Y.-C. Chang, C.-S. Tsai, H.-H. Chou, S.-Y. Ma
Journal: Journal of Clinical Oncology (2004)

9606 Background: Serum squamous cell carcinoma antigen (SCC-Ag) elevation without detectable recurrent lesion during follow-up in cervical cancer patients presents a diagnostic and therapeutic challenge. We evaluated fluorine-18-labeled fluoro-2-deoxy-D-glucose positron emission tomography (PET) in this situation by a prospective trial. Methods: Women with cervical cancer, having completely responded to primary or salvage treatment, had serum SCC-Ag >= 2.0 ng/ml in two consecutive measures and had no evidence of recurrence detected by conventional studies were eligible. Patients with skin lesion(s), documented renal function impairment or pulmonary lesion(s) that might explain the SCC-Ag elevation were excluded. PET was undertaken within 2 weeks after conventional studies. Results: 27 consecutive patients were registered. Positive PET findings were showed in 19 patients: 14 with distant lesion(s), 2 with local lesion(s) and 3 with local and distant lesions. 17 patients with positive PET findings were confirmed to have disease recurrence and another two were free of recurrence but had severe anthracosis in the positive mediastinal nodes. 7 of the 8 patients with negative PET did not recur at follow-up. 7 patients with recurrence received curative-intended therapies and complete response was achieved in 6 patients, in whom 4 were currently alive without disease. Compared to a historical group of 30 patients with elevated SCC-Ag as the first sign of recurrence, the adding of PET reduced the usage of futile curative therapy and significantly increased patients' overall survival. Conclusions: PET expedited the detection of recurrences in patients with unexplained SCC-Ag elevation and lead to an improvement in patients' survival. No significant financial relationships to disclose.
Benefit of Early Switch to Liposomal Amphotericin B in Patients with Amphotericin B Deoxycholate-Induced Nephrotoxicity Versus Late Switch.
Authors: Françoise Isnard, Jean P. Laporte, Patrice Chevallier, Arnaud Pigneux, Patrick Tilleul, Antoine Lafuma, Lamine Mahi, Gilbert Deray
Journal: Blood (2005)
Safety and Efficacy of Bendamustine with or without Rituximab for the Treatment of Heavily Pretreated CLL and Lymphoma Patients. A Multicenter Retrospective Study.
Authors: Luigi Rigacci, Benedetta Puccini, Enrico Orciuolo, Alfonso D'Arco, Sergio Storti, Gianluca Gaidano, Roberto Freilone, Nicola Di Renzo, Caterina Patti, Alessandro Isidori, Pier Luigi Zinzani, Marco Gobbi, Pellegrino Musto, Anna Marina Liberati, Andrea Carpaneto, Sergio Cortelazzo, Nicola Cascavilla, Nadia Cecconi, Valeria Belsito Petrizzi, Giulio Giordano, Silvia Franceschetti, Atto Billio, Alberto Bosi
Journal: Blood (2009)
‘Microbes in sport’ – The potential role of the gut microbiota in athlete health and performance
Authors: Alan Rankin, Ciara O’Donavon, Sharon M Madigan, Orla O’Sullivan, Paul D Cotter
Journal: British Journal of Sports Medicine (2017)

The human intestinal tract is home to approximately 100 trillion microbes with the majority of these residing in the colon. Most microbes in the human intestinal tract are bacteria but archaea, fungi, protozoans and a large population of viruses are also present.1 These microbes have a vast array of functions including vitamin production, fibre digestion, interacting with the immune system2 3 and they contribute significantly to health and disease.

Previously, it was only possible to study the human gut microbiota (GM; microbiota refers to the assemblage of microorganisms present in a defined environment) after first culturing the microbes on agar plates. Gut microbes have an extremely specific set of growth conditions in vivo that are difficult to recreate in a lab environment. Advancement in DNA sequencing technology has made it possible to study the genetic material of the microbes present and negates the need for culture.2 Increased understanding of the role of GM has led to innovative methods to alter gut microbe composition and subsequently GM function. Many factors have been shown to influence …
Mutation detection in lung tumors: Comparing high-resolution melting with direct sequencing
Authors: E. H. Lim, C. Hough, J. McKinney, S. Zhang, R. Martin, P. Tan, D. Teng
Journal: Journal of Clinical Oncology (2008)

19021 Background: Most lung cancers are diagnosed in the advanced stage and not treated surgically. Hence, molecular analysis of lung tissue is limited to the low-volume biopsies obtained at diagnosis. The influence of somatic mutations in guiding treatment decisions, e.g. tyrosine kinase inhibitors (TKI) in epidermal growth factor receptor (EGFR) mutants, has intensified the exploration of methods for improved mutation detection in clinical practice that are sensitive, reliable and fast. Methods: Patients: We studied p53 exons 5–9 (mutation hotspots) in 176 surgically resected non-small cell lung tumors, comparing direct sequencing with high-resolution melting (HRM) analysis. For discordant cases, HRM was repeated, followed by “digital PCR” analyses. DNA sequencing: PCR products were sequenced bidirectionally using ABI PRISM BigDye terminators and the ABI PRISM 3700 genetic analyzer. High-resolution melting: HRM was performed using the 96-well LightScanner system and LCGreen Plus dye (Idaho Technology, USA). Results are obtained in ∼8 minutes. Each assay uses <15 ng of DNA. Variant PCR amplicons were sequenced after melting. Digital PCR analysis: After serial dilution of tumor DNA, 10–20 independent PCRs and HRM were conducted for each sample using one of the p53 HRM assays. Amplicons that displayed variant melt curves in 2 or more reactions were subjected to Sanger sequencing to identify and quantify ones that contained low fractions (<15%) of variant sequences. Results: Of 98 reactions that showed non-wild type results by either method, 66 were concordant, 28 were discordant, 3 and 1 yielded no results from direct sequencing and HRM, respectively. After repeat HRM and digital PCR of the 28 discordant samples, 17 confirmed the HRM results, 10 confirmed the direct sequencing results; 1 remained unresolved. False negative rates for direct sequencing and HRM were 15% and 4%, respectively; the false positive rate for HRM was 0.8%. In 6 cases of the 17 confirmed HRM results, the proportion of mutant alleles was <10%, highlighting HRM’s high sensitivity. Conclusions: HRM is a sensitive and fast method of mutation detection. The low usage of DNA makes it attractive for future investigation in low-volume lung biopsies. No significant financial relationships to disclose.
Array CGH Analysis of Chronic Lymphocytic Leukemia Reveals Frequent Cryptic Monoallelic and Biallelic Deletions of Chromosome 22q11.
Authors: William D. McClain, Shelly R. Gunn, Aswani R. Bolla, Lynn L. Barron, Mercedes E. Gorre, David W. Bahler, Clemens H. M. Mellink, Marinus H. J. van Oers, Michael J. Keating, Alessandra Ferrajoli, Kevin R. Coombes, Lynne V Abruzzo, Ryan S. Robetorye
Journal: Blood (2008)
Tests of Glycemia in Diabetes
Journal: Diabetes Care (2002)

Monitoring of glycemic status, as performed by patients and health care providers, is considered a cornerstone of diabetes care.Results of monitoring are used to assess the efficacy of therapy and to guide adjustments in medical nutrition therapy (MNT), exercise, and medications to achieve the best possible blood glucose control.This position statement presents the recommendations of the American Diabetes Association on the tests used most widely in monitoring the glycemic status of people with diabetes and addresses both patient and physician/laboratorybased testing.It does not address tests for diabetes screening and diagnosis.The recommendations are based on the American Diabetes Association's technical review on the subject, which should be consulted for further information (1). BLOOD GLUCOSE TESTINGBY PATIENTS -Within only a few years, self-monitoring of blood glucose (SMBG) by patients has revolutionized management of diabetes.Using SMBG, patients with diabetes can work to achieve and maintain specific glycemic goals.Given the results of the Diabetes Control and Complications Trial (DCCT) and other studies, there is broad consensus on the health benefits of normal or nearnormal blood glucose levels and on the importance, especially in insulin-treated patients, of SMBG in treatment efforts designed to achieve such glycemic goals.The subject of SMBG has been addressed extensively by two American Diabetes Association Consensus Conferences, which provide a comprehensive review of the subject (2,3).
An open-label, dose escalation, safety, and pharmacokinetic study of ENMD-2076 administered orally to patients with advanced cancer
Authors: B. R. Bastos, J. Diamond, R. Hansen, D. Gustafson, J. Arnott, M. Bray, C. Sidor, W. Messersmith, G. Shapiro
Journal: Journal of Clinical Oncology (2009)

3520 Background: ENMD-2076, a novel, orally-active antimitotic and antiangiogenic molecule inhibits Aurora A as well as tyrosine kinases that drive tumor vascularization, including VEGFR2 (KDR), PDGFR and the FGF receptors. This Phase 1 study was designed to evaluate the safety, pharmacokinetics (PK) and preliminary efficacy of ENMD-2076 administered once daily to patients (pts) with advanced cancer. Methods: The dose escalation scheme utilizes 3 (or 4) + 3 (or 2) design. Pts receive ENMD-2076 once daily in 28-day cycles (followed by 7–14 days of rest between cycles 1 and cycle 2 only). Results: 14 pts have been enrolled in 3 dose cohorts (range 60 to 120 mg/m 2 /d). Median age/performance status is 62/1. The total number of treatment cycles to date is 45, with a median of 3 cycles (range &lt;1 to 9 cycles). Most frequent, related toxicities (all grades, n=14) were hypertension (29%), fatigue (21%), proteinuria and diarrhea (both 14%). One pt experienced dose limiting toxicity of Grade 4 hypertension and Grade 3 cholecystitis in the first dose cohort of 60 mg/m 2 /d. Following drug interruption, the pt restarted at 30 mg/m 2 /d and continued for 4 additional cycles before being removed for progressive disease. Noncompartmental PK analysis of the first two dose levels shows that the plasma concentration of ENMD-981693 (the active free base of ENMD-2076) is dose- linear, as reflected in AUC and C max . The estimated terminal half-life (t 1/2 ) is unaltered regardless of dose; however, t 1/2 is approximately 50% greater at steady state than following single dose administration. Four ovarian cancer and 2 colon cancer pts have achieved decreases ranging from 11–61% in either CA125 or CEA, respectively (4 are associated with stable disease at Cycle 2 by modified RECIST criteria). Serum KDR concentrations assayed by ELISA decreased from baseline in all patients on treatment from a mean of 9153 pg/mL (SEM 464.2) at D1 to 6987 pg/mL (SEM 460.0) at D28 (p &lt;0.05). Conclusions: ENMD-2076 is a small molecule kinase inhibitor with acceptable toxicity and preliminary evidence of antitumor activity in pts with ovarian and colorectal cancers. [Table: see text]
Abnormal ECG, Seizures, and Associated Neurological Deficits
Authors: James A. Reiffel
Journal: Circulation (2017)

ECG CHALLENGEIn the early 1980s, a 17-year-old girl and her mother were referred to me.The mother had a life-long history of seizures-ultimately well controlled with phenytoin-but she had never had an ECG.Her daughter began to have seizures in late childhood, several times per year, 1 of which was particularly prolonged and left her with a new, permanent neurological disorder impairing motor skills, comprehension, and memory.Two years before the referral, the daughter had an ECG, after which her seizure medications were changed to phenytoin.The ECG is shown in Figure 1.What abnormalities are present and how, if at all, might they relate to the seizures?Would you continue to treat her with phenytoin, or would you change to another agent, and if so, which?Please turn the page to read the diagnosis.
The Use of FDG-PET in the Initial Staging of Patients with Follicular Lymphoma (FL). A Retrospective Study From the Fondazione Italiana Linfomi
Authors: Stefano Luminari, Quaresima Micol, Versari Annibale, Luca Arcaini, Chiara Rusconi, Andrea Gallamini, Francesco Merli, Michele Spina, Andrés J.M. Ferreri, Pier Luigi Zinzani, Barbara Botto, Gianluca Gaidano, D'Arco Alfonso, Francesco Di Raimondo, Angelo Michele Carella, Savina Aversa, Caterina Stelitano, Pellegrino Musto, Graziella Pinotti, Roberto Freilone, Riccardo Centurioni, Fortunato Morabito, Giovanni Bertoldero, Massimo Fabrizio Martelli, Stefan Hohaus, Matteo Dell'Olio, Petti Concetta, Armando Santoro, Massimo Federico
Journal: Blood (2011)