tbuckley/cabot-search huggingface dataset:
Short- and long-term benefits of lenalidomide treatment in patients with lower-risk del(5q) myelodysplastic syndromes
Authors: R.S. Komrokji, A.F. List
Journal: Annals of Oncology (2015)

The treatment of patients with myelodysplastic syndromes (MDS) begins with assessment of karyotype and risk. Lenalidomide is approved for the treatment of patients who have transfusion-dependent anemia due to lower-risk MDS with chromosome 5q deletion (del(5q)) with or without additional cytogenetic abnormalities, and isolated del(5q) only in the European Union. Mounting evidence suggests that lenalidomide is effective not only in reducing red blood cell (RBC) transfusion burden, but also in modifying the disease natural history by suppressing the malignant clone. Data discussed here from the pivotal phase 2 (MDS-003) and phase 3 (MDS-004) studies of lenalidomide demonstrate that lenalidomide treatment was associated with both short- and long-term benefits. These clinical benefits included high rates of RBC-transfusion independence (TI) with prolonged durations of response, high rates of cytogenetic response (CyR) associated with achievement of durable RBC-TI, no significant difference in rates of progression to acute myeloid leukemia (AML), and improvements in health-related quality of life (HRQOL). Achievement of RBC-TI and CyR with lenalidomide treatment was associated with extended survival and time to AML progression. Achievement of RBC-TI and hemoglobin response was additionally associated with HRQOL benefits. Recent data describing the impact of TP53 mutations and p53 expression on the prognosis of patients with del(5q) and the impact on response to lenalidomide are also discussed. The authors provide practical recommendations for the use of lenalidomide in patients with lower-risk del(5q) MDS.
Prevention of conversion to abnormal transcranial <scp>D</scp>oppler with hydroxyurea in sickle cell anemia: A <scp>P</scp>hase III international randomized clinical trial
Authors: Jane S. Hankins, Mary Beth McCarville, Angela Rankine‐Mullings, Marvin E. Reid, Clarisse L.C. Lobo, Patricia G. Moura, Susanna Ali, Deanne P. Soares, Karen Aldred, Dennis W. Jay, Banu Aygun, John Bennett, Guolian Kang, Jonathan C. Goldsmith, Matthew P. Smeltzer, James M. Boyett, Russell E. Ware
Journal: American Journal of Hematology (2015)

Children with sickle cell anemia (SCA) and conditional transcranial Doppler (TCD) ultrasound velocities (170-199 cm/sec) may develop stroke. However, with limited available clinical data, the current standard of care for conditional TCD velocities is observation. The efficacy of hydroxyurea in preventing conversion from conditional to abnormal TCD (≥200 cm/sec), which confers a higher stroke risk, has not been studied prospectively in a randomized trial. Sparing Conversion to Abnormal TCD Elevation (SCATE #NCT01531387) was a National Heart, Lung, and Blood Institute-funded Phase III multicenter international clinical trial comparing alternative therapy (hydroxyurea) to standard care (observation) to prevent conversion from conditional to abnormal TCD velocity in children with SCA. SCATE enrolled 38 children from the United States, Jamaica, and Brazil [HbSS (36), HbSβ(0) -thalassemia (1), and HbSD (1), median age = 5.4 years (range, 2.7-9.8)]. Because of the slow patient accrual and administrative delays, SCATE was terminated early. In an intention-to-treat analysis, the cumulative incidence of abnormal conversion was 9% (95% CI = 0-35%) in the hydroxyurea arm and 47% (95% CI = 6-81%) in observation arm at 15 months (P = 0.16). In post hoc analysis according to treatment received, significantly fewer children on hydroxyurea converted to abnormal TCD velocities when compared with observation (0% vs. 50%, P = 0.02). After a mean of 10.1 months, a significant change in mean TCD velocity was observed with hydroxyurea treatment (-15.5 vs. +10.2 cm/sec, P = 0.02). No stroke events occurred in either arm. Hydroxyurea reduces TCD velocities in children with SCA and conditional velocities.
Impact of Antipsychotic Review and Nonpharmacological Intervention on Antipsychotic Use, Neuropsychiatric Symptoms, and Mortality in People With Dementia Living in Nursing Homes: A Factorial Cluster-Randomized Controlled Trial by the Well-Being and Health for People With Dementia (WHELD) Program
Authors: Clive Ballard, Martin Orrell, Sun YongZhong, Esme Moniz-Cook, Jane Stafford, Rhiannon Whittaker, Bob Woods, Anne Corbett, Lucy Garrod, Zunera Khan, Barbara Woodward-Carlton, Jennifer Wenborn, Jane Fossey
Journal: American Journal of Psychiatry (2015)

Objective: This study evaluated the impact of antipsychotic review, social interaction, and exercise, in conjunction with person-centered care, on antipsychotic use, agitation, and depression in people with dementia living in nursing homes. Method: A cluster-randomized factorial controlled trial with two replications was conducted in people with dementia in 16 U.K. nursing homes. All homes received training in person-centered care. Eight homes were randomly assigned to antipsychotic review, to a social interaction intervention, and to an exercise intervention for 9 months, with most homes assigned to more than one intervention. The primary outcome measures were antipsychotic use, agitation, and depression. Secondary outcome measures were overall neuropsychiatric symptoms and mortality. Results: Antipsychotic review significantly reduced antipsychotic use by 50% (odds ratio 0.17, 95% confidence interval [CI] 0.05 to 0.60). Antipsychotic review plus the social interaction intervention significantly reduced mortality (odds ratio 0.26, 95% CI 0.13 to 0.51) compared with the group receiving neither. The group receiving antipsychotic review but not the social intervention showed significantly worse outcome in neuropsychiatric symptoms compared with the group receiving neither (score difference +7.37, 95% CI 1.53 to 13.22). This detrimental impact was mitigated by concurrent delivery of the social intervention (−0.44, CI −4.39 to 3.52). The exercise intervention significantly improved neuropsychiatric symptoms (−3.59, 95% CI −7.08 to −0.09) but not depression (−1.21, CI −4.35 to 1.93). None of the interventions had a significant impact specifically on agitation. Conclusions: While reductions in antipsychotic use can be achieved by using a "real world" intervention, this may not be of benefit to people with dementia in the current climate of more judicious prescribing unless nonpharmacological interventions such as social interaction or exercise are provided in parallel.
Optogenetic acidification of synaptic vesicles and lysosomes
Authors: Benjamin R Rost, Franziska Schneider, M Katharina Grauel, Christian Wozny, Claudia G Bentz, Anja Blessing, Tanja Rosenmund, Thomas J Jentsch, Dietmar Schmitz, Peter Hegemann, Christian Rosenmund
Journal: Nature Neuroscience (2015)
[3H]N-[4-(3,4-dihydro-6,7-dimethoxyisoquinolin-2(1H)-yl)butyl]-2-methoxy-5-methylbenzamide: a novel sigma-2 receptor probe
Authors: Jinbin Xu, Zhude Tu, Lynne A. Jones, Kenneth T. Wheeler, Robert H. Mach
Journal: Cancer Research (2005)

Proc Amer Assoc Cancer Res, Volume 46, 2005

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N -[4-(3,4-dihydro-6,7-dimethoxyisoquinolin-2(1H)- yl )butyl]-2-methoxy-5-methyl-benzamide (RHM-1) and N -[2-(3,4-dihydro-6,7-dimethoxyisoquinolin-2(1H)- y l)ethyl]-2-methoxy-5-methylbenzamide (RHM-2), two conformationally-flexible benzamide analogues, have been shown to have high affinity and selectivity for σ2 receptors versus σ1 and the dopamine D2 and D3 receptors ( Bioorg. Med. Chem. Lett. 2004: 14; 195-202). Their high σ2 receptor affinity (Ki   300) indicates that they may be useful radioligands for assessing the σ2 receptor status of solid tumors. Therefore, RHM-1 and RHM-2 were radiolabeled with tritium (specific activity = 80 Ci/mmol) and the binding of [3H]RHM-1 and [3H]RHM-2 to σ2 receptors of rat liver and breast tumor homogenates were evaluated in vitro. [3H]RHM-1 was found to have a higher affinity and higher selectivity for σ2 receptors compared to [3H]RHM-2 and [3H]DTG. [3H]RHM-1 has a dissociation constant (Kd) of 0.66 ± 0.12 nM, which was 30-fold higher affinity than that of [3H]RHM-2 (Kd = 19.48 ± 0.51 nM). The Kd values obtained from saturation binding experiments are consistent with the results that are calculated from kinetic (i.e., kon and koff) studies. The lower affinity of [3H]RHM-2 is attributed to its faster koff rate since both radioligands have similar kon rates. [3H]RHM-2 appears to have a similar binding affinity to that of 3H-DTG, both of which dissociate from σ2 receptors faster than [3H]RHM-1. Competitive binding assays were also conducted using a series of σ1, σ2, dopaminergic, serotonergic and NMDA drugs and both [3H]RHM-1 and [3H]DTG. The pharmacologic profile of [3H]RHM-1 was in agreement with that of [3H]DTG. Scatchard studies of [3H]RHM-1 were also conducted with membrane homogenates from MDA-MB 435 human breast tumors and EMT-6 mouse breast tumors. The density of σ2 receptors was found to be high in both tumors. These data suggest that [3H]RHM-1 is a useful radioligand for assessing the σ2 receptor status of solid tumors. Research funded by CA 102869 and DAMD17-01-0446.
Repeat peroral endoscopic myotomy: a salvage option for persistent/recurrent symptoms
Authors: Quan-Lin Li, Li-Qing Yao, Xiao-Yue Xu, Jun-Yu Zhu, Mei-Dong Xu, Yi-Qun Zhang, Wei-Feng Chen, Ping-Hong Zhou
Journal: Endoscopy (2015)

<b>Background and study aims: </b>Although peroral endoscopic myotomy (POEM) is credited with high success rates in the treatment of achalasia, persistent/recurrent symptoms may occasionally develop afterwards. Our purpose was to evaluate the feasibility, safety, and efficacy of repeat peroral endoscopic myotomy (Re-POEM) as salvage therapy after initial POEM failure. <b>Patients and methods:</b> Fifteen patients with persistence/recurrence of symptoms after previous POEM (Eckardt symptom score ≥ 4) were retrospectively selected from a prospectively maintained database housing a total of 1454 consecutive patients with achalasia. The primary endpoint was symptom relief during follow-up, defined by an Eckardt score of ≤ 3. Secondary outcome measures were procedure-related adverse events, change in manometric lower esophageal sphincter (LES) pressure, and reflux symptoms before and after Re-POEM. <b>Results: </b>All patients underwent successful Re-POEM a mean of 13.5 months (range 4 – 37 months) after execution of their primary POEM procedures. Mean operative time was 41.5 minutes (range 28 – 62 minutes). One instance of submucosal tunnel infection was successfully managed with conservative treatment. During a mean follow-up period of 11.3 months (range 3 – 18 months), therapeutic success was achieved in all patients. The mean symptom score pretreatment was 5.6 (range 4 – 8), compared with a post-treatment mean of 1.2 (range 0 – 3; <i>P</i> < 0.001). Mean LES pressure also declined from 25.0 mmHg to 9.5 mmHg after Re-POEM (<i>P</i> < 0.001). The overall clinical reflux complication rate of Re-POEM was 33.3 %. <b>Conclusions: </b>Re-POEM appears safe and effective as a salvage option after initial POEM failure, conferring short-term symptom relief and being free of serious complications in all patients.
StatFlu - a static modelling tool for pandemic influenza hospital load for decision makers
Authors: M Camitz
Journal: Eurosurveillance (2009)

We provide a new tool, StatFlu, combining advances in static modelling using historic influenza data with a pedagogical interface designed to highlight propagation of parameter settings and uncertainties in the output. StatFlu provides graphs of the load on hospital wards as well as primary care units as a function of time, aiding the user in decision making.
Economic Impact of Harmonizing Medical Practices: Compliance With Clinical Practice Guidelines in the Follow-Up of Breast Cancer in a French Comprehensive Cancer Center
Authors: Dominique Mille, Thomas Roy, Marie-Odile Carrère, Isabelle Ray, Nora Ferdjaoui, Hans-Martin Späth, Franck Chauvin, Thierry Philip
Journal: Journal of Clinical Oncology (2000)

The introduction of clinical practice guidelines (CPGs) and the increasing desire to harmonize clinical practices draw attention to the economic impact of these trends. In 1994, CPGs were introduced in a French Comprehensive Cancer Center (Centre Régional Léon Bérard, Lyon). We evaluated the application of these CPGs in addition to the consequences of harmonizing clinical practices with respect to the distribution of resources by specifically analyzing the posttherapeutic follow-up of patients with localized breast cancer.A before-and-after analysis of the records of patients who received posttherapeutic follow-up for localized breast cancer as of either 1993 or 1995 was performed. Two hundred records were chosen at random, 100 from 1993 and 100 from 1995. Follow-up was continued for as long as possible and CPG compliance was studied for each year of the follow-up periods.Follow-up that was not CPG-compliant required a significantly greater amount of resources. This difference was due to neither consultations nor mammographies, but was due to other examinations that were systematically performed without any warning signs to justify them. Depending on the follow-up year, noncompliant follow-up cost the Social Security from 2.2 to 3.6 times more than compliant follow-up. A noticeable change in medical practices was observed after the introduction of CPGs in 1994. This was confirmed by a sharp decrease in mean Social Security expenditure per patient of more than one third between 1993 and 1995, regardless of the follow-up year considered.In the follow-up of patients with localized breast cancer, a large decrease in costs has been observed along with the evolution of medical practices toward CPG compliance. This finding is probably generalizable to other settings, but there is nothing that proves that it is applicable to other treatment strategies.
Phase 1/2 Study Of Brentuximab Vedotin In Pediatric Patients With Relapsed Or Refractory (R/R) Hodgkin Lymphoma (HL) Or Systemic Anaplastic Large-Cell Lymphoma (sALCL): Preliminary Phase 2 Data For Brentuximab Vedotin 1.8 Mg/Kg In The HL Study Arm
Authors: Franco Locatelli, Kathleen A Neville, Angelo Rosolen, Judith Landman-Parker, Nathalie Aladjidi, Auke Beishuizen, Stephen Daw, Lia Gore, Anna R.K. Franklin, Adedigbo Fasanmade, Jingyuan Wang, Jessica Sachs, Christine Mauz-Koerholz
Journal: Blood (2013)
Life expectancy of young adults with follicular lymphoma
Authors: A. Conconi, C. Lobetti-Bodoni, S. Montoto, A. Lopez-Guillermo, R. Coutinho, J. Matthews, S. Franceschetti, F. Bertoni, A. Moccia, P.M.V. Rancoita, J. Gribben, F. Cavalli, G. Gaidano, T.A. Lister, E. Montserrat, M. Ghielmini, E. Zucca
Journal: Annals of Oncology (2015)
Unraveling the Genetic Basis of Seahorse Male Pregnancy
Authors: J. Caspermeyer
Journal: Molecular Biology and Evolution (2015)

For seahorses, a unique mode of reproduction—male pregnancy—closely resembles the pregnancy of female mammals, including humans. In a new study, corresponding author Wilson and an international team of researchers have taken a major step toward answering the question of whether the structures of complex reproductive systems—like the seahorse’s—reflect a common genetic architecture. “Scientists have long been fascinated with the unique form of reproduction in the seahorse, and we were interested in understanding just how seahorse pregnancy takes place,” said Wilson. “Our findings provide a unique perspective on the origins of internal reproduction in animals. We were surprised to learn that reproductive systems across species are not only superficially similar, but are also controlled in much the same way.” Male seahorses carry offspring in the brood pouch, which is functionally equivalent to the mammalian uterus. Whittington et al. (2015) tracked brood pouch gene activity of pot-bellied seahorses (Hippocampus abdominalis) over the duration of pregnancy and identified critical genetic changes. A systematic comparison between the seahorse genes and reproduction in mammals, reptiles, and fishes revealed that many of the key genes are identical across species, a result that suggests the existence of a common evolutionary toolkit associated with internal reproduction. “While the presence of these genes in all species reflects their common ancestry,” noted Wilson, “their repeated recruitment into reproduction suggests that diverse lineages of animals have overcome the challenges of pregnancy in similar ways. Genetic studies such as ours emphasize how the shared evolutionary ancestry of animals may help to facilitate the origin of new organ systems.” Next, the team will continue their work on the genetic basis of male pregnancy and study the genetic regulation of reproduction in species with more rudimentary forms of male pregnancy.
Straight talk with...Jeremy Farrar
Authors: Jeremy Farrar, Daniel Cressey
Journal: Nature Medicine (2014)

Jeremy Farrar is no stranger to running a charitable organization. In 2011, the clinician-scientist and avid cricket player launched the Farrar Foundation, which spends around £9,000 ($15,000) per year supporting medical and sporting activities in Southeast Asia. As director of the Oxford University Clinical Research Unit, based in Ho Chi Minh City, Vietnam, Farrar wanted to give something back to the people he had worked with in region. Now, he is taking his research and philanthropic agendas to a global level. On 1 October, Farrar took the helm of the Wellcome Trust, the second largest nongovernmental funder of biomedical research in the world.It's a natural fit for the Wellcome Trust and Farrar alike—Farrar has leadership experience in the global health arena and the Trust has supported much of his research into dengue, typhoid and other tropical diseases. But the Wellcome Trust, with its £16 billion endowment, is far more than just an enabler of biomedical research. It is also a key player in wider science policy debates, driving forward agendas such as open access while also maintaining active programs of public engagement. Farrar sat down with Daniel Cressey at the Wellcome headquarters in London to discuss his Trust issues.
Psychogenic factors in predicting survival of breast cancer patients.
Authors: R N Jamison, T G Burish, K A Wallston
Journal: Journal of Clinical Oncology (1987)

Considerable controversy and contradictory data exist about the notion that psychosocial factors can predict longevity in cancer patients. This study further addresses that issue by eliminating some of the methodological weaknesses of prior studies and focusing on a more tightly defined patient population. Forty-nine female metastatic breast cancer patients were given a variety of psychological tests. At the time of the analyses, all patients in the study had died from their disease. Patients were evenly divided into short-term survivors and long-term survivors based on length of survival as calculated both from date of diagnosis and from date of testing. The results indicated that there were no consistent differences between groups on any psychosocial variable assessed. These data suggest that, for breast cancer patients with metastatic disease, disease-related variables probably outweigh the influence of select psychosocial factors in determining length of survival.
The Ubiquitin Proteome of Toxoplasma gondii Reveals Roles for Protein Ubiquitination in Cell-Cycle Transitions
Authors: Natalie C. Silmon de Monerri, Rama R. Yakubu, Allan L. Chen, Peter J. Bradley, Edward Nieves, Louis M. Weiss, Kami Kim
Journal: Cell Host & Microbe (2015)
Should women take part in clinical trials in breast cancer? Issues and some solutions.
Authors: J Cockburn, S Redman, A Kricker
Journal: Journal of Clinical Oncology (1998)

PURPOSE The purpose of this review is to consider the issues for women related to participation in clinical trials that evaluate the management of breast cancer and provide some recommendations for future initiatives to address the identified areas of concern. METHODS The National Health and Medical Research Council (NHMRC) National Breast Cancer Centre hosted an international workshop to address the question "Clinical Trials in Breast Cancer: Should Women Take Part?" We also reviewed the literature on informed participation in clinical trials that was identified in a broadly based search that covered Medline, PsycLIT, and HealthPlan from 1986 to 1996. RESULTS AND CONCLUSION When women are asked to participate in a clinical trial, they are faced with a number of questions and dilemmas. These include issues related to the conduct and ethical considerations of the trial; the effect of participation or nonparticipation on treatment; the roles of the doctor as clinician and as researcher; the process of informed consent; the timing of the request for participation; and the benefits and costs of participation. A number of steps are identified that could help women decide whether to participate in clinical trials. These include provision of community information about clinical trials; establishment of independent brokers and registers for clinical trials; consumer review of information and protocols and involvement in trials; review of the role of ethics committees; collection of data about the proportion of women currently recruited to clinical trials, their reasons for participating or declining, and their views about the process of recruitment and participation; models for optimal practice in recruiting women to clinical trials and encouraging ongoing participation in trials; evidence-based communication skills training for clinicians to teach skills to inform women adequately of clinical trial participation; and auspicing and promotion of trials by an independent agency.