tbuckley/cabot-search huggingface dataset:
Estimating the Ages of Selection Signals from Different Epochs in Human History
Authors: Shigeki Nakagome, Gorka Alkorta-Aranburu, Roberto Amato, Bryan Howie, Benjamin M. Peter, Richard R. Hudson, Anna Di Rienzo
Journal: Molecular Biology and Evolution (2015)

Genetic variation harbors signatures of natural selection driven by selective pressures that are often unknown. Estimating the ages of selection signals may allow reconstructing the history of environmental changes that shaped human phenotypes and diseases. We have developed an approximate Bayesian computation (ABC) approach to estimate allele ages under a model of selection on new mutations and under demographic models appropriate for human populations. We have applied it to two resequencing data sets: An ultra-high depth data set from a relatively small sample of unrelated individuals and a lower depth data set in a larger sample with transmission information. In addition to evaluating the accuracy of our method based on simulations, for each SNP, we assessed the consistency between the posterior probabilities estimated by the ABC approach and the ancient DNA record, finding good agreement between the two types of data and methods. Applying this ABC approach to data for eight single nucleotide polymorphisms (SNPs), we were able to rule out an onset of selection prior to the dispersal out-of-Africa for three of them and more recent than the spread of agriculture for an additional three SNPs.
Brief Report: Cartilage Thickness Change as an Imaging Biomarker of Knee Osteoarthritis Progression: Data From the Foundation for the National Institutes of Health Osteoarthritis Biomarkers Consortium
Authors: F. Eckstein, J. E. Collins, M. C. Nevitt, J. A. Lynch, V. B. Kraus, J. N. Katz, E. Losina, W. Wirth, A. Guermazi, F. W. Roemer, D. J. Hunter
Journal: Arthritis & Rheumatology (2015)

To investigate the association of cartilage thickness change over 24 months, as determined by magnetic resonance imaging (MRI), with knee osteoarthritis (OA) progression at 24-48 months.This nested case-control study included 600 knees with a baseline Kellgren/Lawrence (K/L) grade of 1-3 from 600 Osteoarthritis Initiative (OAI) participants. Case knees (n = 194) had both medial tibiofemoral radiographic joint space loss (≥0.7 mm) and a persistent increase in the Western Ontario and McMaster Universities Osteoarthritis Index pain score (≥9 on a 0-100 scale) 24-48 months from baseline. Control knees (n = 406) included 200 with neither radiographic nor pain progression, 103 with radiographic progression only, and 103 with pain progression only. Medial and lateral femorotibial cartilage was segmented from sagittal 3T MRIs at baseline, 12 months, and 24 months. Logistic regression was used to assess the association of change in cartilage thickness, with a focus on the central medial femorotibial compartment, and OA progression.Central medial femorotibial compartment thickness loss was significantly associated with case status, with an odds ratio (OR) of 1.9 (95% confidence interval [95% CI] 1.6-2.3) (P < 0.0001). Association with case status reached P < 0.05 for both the central femur (OR 1.8 [95% CI 1.5-2.2]) and the central tibia (OR 1.6 [95% CI 1.3-1.9]). Lateral femorotibial compartment cartilage thickness loss, in contrast, was not significantly associated with case status. A reduction in central medial femorotibial compartment cartilage thickness was strongly associated with radiographic progression (OR 4.0 [95% CI 2.9-5.3]; P < 0.0001) and only weakly associated with pain progression (OR 1.3 [95% CI 1.1-1.6]; P < 0.01).Our findings indicate that loss of medial femorotibial cartilage thickness over 24 months is associated with the combination of radiographic and pain progression in the knee, with a stronger association for radiographic progression.
Managed Care &amp; Medical Oncology: The Focus is on Value
Authors: Elizabeth Danielson, Jessica DeMartino, Jill A. Mullen
Journal: Journal of the National Comprehensive Cancer Network (2010)

A previous NCCN Oncology Insights Reportdescribed the factors making cancer care a priority for managed care organizations (MCOs) and emerging trends in managing costs of cancer care. To better understand the concerns of MCOs and how they are addressing cancer costs and quality, NCCN interviewed senior physician executives from the 3 largest payors in the United States. The interviews provided insights into how these companies managed oncology care, with an emphasis on drugs and biologics. As a follow-up to the previous report, NCCN conducted additional interviews with medical executives from 10 MCOs between February and April 2010. The organizations represented in these interviews were Aetna, BlueCross BlueShield of Minnesota, BlueShield of Michigan, CareFirst BlueCross BlueShield, Empire BlueCross BlueShield, HealthNow, Humana, Independence BlueCross, Priority Health, and UnitedHealthcare. Although this group is diverse, it does not constitute a representative cross-section of MCOs across the United States. NCCN interviewed these executives about the priority of cancer care management for their organizations and the strategies being used to address cost and quality of cancer care. The information garnered from these interviews was qualitative in nature. A separate quantitative analysis of trends in oncology managed care has already been published, and throughout this report, data from the 2009-2010 Genentech Oncology Trend Report are referenced to supplement findings from the NCCN interviews.
S-1 plus leucovorin versus S-1 plus leucovorin and oxaliplatin versus S-1 plus cisplatin in patients with advanced gastric cancer: a randomised, multicentre, open-label, phase 2 trial
Authors: Shuichi Hironaka, Naotoshi Sugimoto, Kensei Yamaguchi, Toshikazu Moriwaki, Yoshito Komatsu, Tomohiro Nishina, Akihito Tsuji, Takako Eguchi Nakajima, Masahiro Gotoh, Nozomu Machida, Hideaki Bando, Taito Esaki, Yasunori Emi, Takashi Sekikawa, Shigemi Matsumoto, Masahiro Takeuchi, Narikazu Boku, Hideo Baba, Ichinosuke Hyodo
Journal: The Lancet Oncology (2015)
Challenging Lung Carcinoma with Coexistent ΔNp63/p40 and Thyroid Transcription Factor-1 Labeling Within the Same Individual Tumor Cells
Authors: Giuseppe Pelosi, Alessandra Fabbri, Elena Tamborini, Federica Perrone, Adele M. Testi, Giulio Settanni, Adele Busico, Giovanni Centonze, Paola Braidotti, Gaetano Bulfamante, Filippo De Braud, Marina Garassino, Ugo Pastorino
Journal: Journal of Thoracic Oncology (2015)
Analysis of the gene encoding the multifunctional alcohol dehydrogenase allozyme ADH-71k of Drosophila melanogaster.
Authors: K T Eisses, A J Andriesse, A Douwe de Boer, G E Thörig, P J Weisbeek
Journal: Molecular Biology and Evolution (1990)

The nucleotide sequence of the alcohol dehydrogenase gene Adh71k has been determined. The Adh71k allele encodes the thermostable and multifunctional ADH-71k allozyme of Drosophila melanogaster. Comparison with the sequences of AdhS, AdhF, and AdhFChD reveals differences in the coding and noncoding regions of the gene. Conceptual translation of the Adh71k sequence indicates that ADH-71k shares with ADH-F and ADH-FCHD an amino acid replacement at residue 192 and with ADH-FCHD an additional replacement of serine for proline at residue 214. Three unique differences were found in the nontranslated regions. It is proposed that a nucleotide deletion in the adult intron is related to the difference in expression level of the Adh71k allele, relative to the other alleles. An insertion of five nucleotides, additional to a single base deletion at that site, was detected in one of the larval enhancer regions in the 5' flanking region of the Adh71k allele, creating a palindromic structure in that area.
Standard Clinical Practice of Folfirinox (Ffx) in Advanced/Metastatic Pancreatic Cancer (Pc) Patients: a Canadian Retrospective Registry
Authors: J.A. Maroun, Y. Ko, A. Ghafoor, P. Kavan, M. Cripps, D. Jonker, R. Goel, T.R. Asmis, R. Goodwin, E. Tsvetkova, H. Marginean
Journal: Annals of Oncology (2014)
Nausea and vomiting in palliative care
Authors: Emily Collis, Harriet Mather
Journal: BMJ (2015)

Cough intensity can be defined with a variety of measures that include thoracic and abdominal pressure, airflow, electromyography and subjective scales. Little is known about cough intensity in patients with chronic cough. We investigated the physiological characteristics of cough intensity in patients with chronic cough and normal subjects. 15 patients with chronic cough and 14 healthy subjects underwent measurements of oesophageal pressure (Poes), gastric pressure (Pga), peak cough flow rate (PCFR), abdominal electromyographic activity and cough sound during voluntary coughs. The data from maximum cough efforts are presented. PCFR was normalised to predicted peak expiratory flow rate to account for gender and height differences. There was no significant difference in gender, age or lung function between patient and control groups. Maximum cough Poes was higher in patients with chronic cough than controls (188 vs 146cmH2O, p=0.02). This difference was limited to females only; the male group was underpowered to detect a difference. Cough Pga (p=0.01) and normalised cough flow (p=0.03) were also higher in female patients than in controls. Female patients with chronic cough have higher maximum cough pressures and cough flows than healthy controls. Further studies are needed to identify underlying mechanisms and investigate whether these findings are also relevant to male patients with chronic cough.
Anorexia nervosa and depression: a dissenting view
Authors: K Z Altshuler, M F Weiner
Journal: American Journal of Psychiatry (1985)

The frequency of depressive symptoms in anorexic patients, the response of some anorexic patients to antidepressants or ECT, the occurrence of comparable physiologic abnormalities in major depression and anorexia nervosa, and family studies of incidence increasingly link depression and anorexia in the literature. A review of the problems in making this linkage shows that the possibility of anorexia nervosa as a depressive equivalent or a depressive spectrum disorder must be seriously questioned.
Induction of T-lymphocyte responses to a small molecular weight antigen. II. specific tolerance induced in azebenzenearsonate (ABA)-specific T cells in Guniea pigs by administration of low doses of an ABA conjugate of chloroacetyl tyrosine in incomplete Freund's adjuvant.
Authors: W W Bullock, D H Katz, B Benacerraf
Journal: The Journal of Experimental Medicine (1975)

The experiments presented in this paper demonstrate that the induction of tolerance on the one hand and the induction of delayed sensitivity on the other hand can be accomplished by administration of similar doses of azobenzene-arsonate conjugated to N-chloracetyl tyrosine (ABA-T) to guinea pigs with the determining factor being the absence or presence, respectively, of activating bacterial products in the adjuvant mixture used. Thus, complete, persistent ABA-T-specific T-cell tolerance can be induced in adult guinea pigs with 20 mug of ABA-T given intradermally in incomplete Freund's adjuvant (IFA) whereas this same dose of ABA-T induces ABA-specific immunity when administered in complete Freund's adjuvant. This tolerance was not reversible by administration of ABA-T and IFA in the presence of bacterial lipopolysaccharide, was generated before the formation of primed T cells, and persisted for at least 3 mo after initiation. Moreover, cell transfer studies performed herein demonstrate that the unresponsiveness resulting from administration of ABA-T in IFA reflects the activity of suppressor cells to induce and maintain a state of unresponsiveness could only be demonstrated in unprimed animals may indicate a severe limitation on the potential clinical usefulness of such an approach to regulation of the immune system.
Evaluating the ASAS recommendations for early referral of axial spondyloarthritis in patients with chronic low back pain; is one parameter present sufficient for primary care practice?
Authors: L van Hoeven, Bart W Koes, Johanna MW Hazes, Angelique EAM Weel
Journal: Annals of the Rheumatic Diseases (2015)

New diagnostic tools and effective treatment for axial spondyloarthritis (axSpA) became available in the last decade. This has raised the need for adequate referral strategies for patients with low back pain suspected of axSpA. However, there is no agreement on which referral strategy is best. Recently, the Assessment of SpondyloArthritis international Society (ASAS) group has published recommendations for the early referral for suspected axSpA1 (box 1). Nonetheless, some critical remarks can be made regarding these recommendations. Box 1 ### The Assessment of SpondyloArthritis international Society (ASAS)-endorsed recommendations for early referral of patients suspected for having axial spondyloarthritis by primary care physicians or non-rheumatologists1
Identification of circulatory biomarkers from clinical trial samples
Authors: Laura Rosa Brunet, Katherine Bodman-Smith, Mark Bodman-Smith, Zain Kassam, Angus Dalgleish, Sam LaBrie, Thorsten Hagemann
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts Despite significant advances in genomics, proteomics and metabolomics, the identification and validation of circulatory immunological biomarkers in cancer patients, which could be useful to monitor disease progression and response to immunotherapeutic treatments, remains as
Response to Letter Regarding Article, “Sudden Cardiac Arrest During Sports Activity in Middle Age”
Authors: Eloi Marijon, Audrey Uy-Evanado, Kyndaron Reinier, Carmen Teodorescu, Kumar Narayanan, Xavier Jouven, Karen Gunson, Jonathan Jui, Sumeet S. Chugh
Journal: Circulation (2015)

We appreciate the interest that Mansencal and colleagues have taken in our paper. 1They pose the question that based on variation in the dynamic and static component of the individual sport, could specific activities pose a higher risk of sudden cardiac arrest (SCA)?Due to several reasons, this important question may be quite difficult to address.Importantly, the relative distribution of different sports associated with SCA is first and foremost a reflection of the frequency of participation in that sport in the population.Therefore, the popularity of the sport will determine the level of participation, and potentially drive the level of association to SCA.There are limited data suggesting that even after taking frequency of participation into account (looking at incidence per million of specific sports participants), some sports, such as cycling, may be associated with a higher risk of SCA. 2,3Another recent report in younger subjects indicated that certain sports, especially basketball, may be associated with higher risk of an SCA event. 4From a practical standpoint we propose that a number of strenuous endurance sports can likely be considered roughly equivalent with respect to risk and benefit.These include, but are not limited to, running, soccer (football), cycling, tennis, swimming, cross country skiing, squash, ice and field hockey, basketball, and rugby.Another confounding factor especially in the context of the general population, is the variable level of risk of the individual participant.Less strenuous sports such as bowling and golf may be less hazardous but the number of high-risk participants may also be greater.The extent to which SCA risk is related to the specifics of the sporting activity versus the characteristics of the participants, is a subject that clearly requires further investigation.Regarding sports-associated SCA in subjects <35 years, given the small population burden we are awaiting feasible numbers of cases to perform a more robust analysis in the Oregon Sudden Unexpected Death Study.In the 2 European prospective studies, carried out in the general population, the incidence of sports SCA in the <35 year age group was estimated to be 3 to 4 per million per year (~10-fold lower compared to the middle age group). 3,5
A phase I and pharmacologic study of DMP 840 administered by 24-hour infusion
Authors: S. O’Reilly, S.D. Baker, S. Sartorius, E.K. Rowinsky, M. Finizio, G.M. Lubiniecki, L.B. Grochow, J.E. Gray, H.I. Pieniaszek, R.C. Donehower
Journal: Annals of Oncology (1998)

DMP 840, a novel bisnaphthalimide, has demonstrated promising schedule dependent anti-tumor activity in vitro and in vivo against several tumor cell lines. A phase I study was conducted to evaluate the effect of a 24-hour infusion schedule repeated every three weeks, on the therapeutic efficacy of DMP 840.Fourteen patients with refractory solid tumor malignancies were treated with DMP 840 at doses of 20, 40, 50 and 60 mg/m2.A combination of neutropenia, thrombocytopenia and stomatitis were dose-limiting at doses of 50 and 60 mg/m2 in both minimally- and extensively-pretreated patients. In contrast, all courses at lower dose levels were well tolerated. Pharmacokinetic analysis demonstrated that DMP 840 had a prolonged terminal half life (median 39 hours; range 25-86) and that dose-limiting events were significantly related to several indices of systemic DMP 840 exposure (P < 0.01, Wilcoxon Rank Sum test).The recommended dose of DMP 840 for further disease oriented evaluations is 40 mg/m2 administered over 24 hours every three weeks. The infusion duration evaluated in this study did not result in a substantial increase in the tolerable dose compared to shorter, less cumbersome schedules.
Bcl-2+ tonsillar plasma cells are rescued from apoptosis by bone marrow fibroblasts.
Authors: P Merville, J Déchanet, A Desmoulière, I Durand, O de Bouteiller, P Garrone, J Banchereau, Y J Liu
Journal: The Journal of Experimental Medicine (1996)

Plasma cells represent the final stage of B lymphocyte differentiation. Most plasma cells in secondary lymphoid tissues live for a few days, whereas those in the lamina propria of mucosa and in bone marrow live for several weeks. To investigate the regulation of human plasma cell survival, plasma cells were isolated from tonsils according to high CD38 and low CD20 expression. Tonsillar plasma cells express CD9, CD19, CD24, CD37, CD40, CD74, and HLA-DR, but not CD10, HLA-DQ, CD28, CD56, and Fas/CD95. Although plasma cells express intracytoplasmic Bcl-2, they undergo swift apoptosis in vitro and do not respond to CD40 triggering. Bone marrow fibroblasts and rheumatoid synoviocytes, however, prevented plasma cells from undergoing apoptosis in a contact-dependent fashion. These data indicate that fibroblasts may form a microenvironment favorable for plasma cell survival under normal and pathological conditions.
Trends in HIV surveillance data in the EU/EEA, 2005 to 2014: new HIV diagnoses still increasing in men who have sex with men
Authors: Anastasia Pharris, Chantal Quinten, Lara Tavoschi, Gianfranco Spiteri, Andrew J. Amato-Gauci
Journal: Eurosurveillance (2015)

Human immunodeficiency virus (HIV) transmission remains significant in Europe. Rates of acquired immunodeficiency syndrome (AIDS) have declined, but not in all countries. New HIV diagnoses have increased among native and foreign-born men who have sex with men. Median CD4 + T-cell count at diagnosis has increased, but not in all groups, and late diagnosis remains common. HIV infection and AIDS can be eliminated in Europe with resolute prevention measures, early diagnosis and access to effective treatment.
Staff in mental health services need clearer guidelines
Authors: D B Double
Journal: BMJ (1996)

EDITOR,—As Simon Wessely describes,1 recent government policy has sought to increase the influence of general practice on secondary services, which has had particular implications for providers of mental health services.2 There has not been a definitive trial of the effectiveness of counselling in general practice,3 but outcome studies are unlikely to be conclusive anyway.4

In this context, mere promotion of the idea that resources should be concentrated on long term mental illness is not good enough because of the temptation …
Macrophage Migration Inhibitory Factor Mediates Proliferative GN via CD74
Authors: Sonja Djudjaj, Hongqi Lue, Song Rong, Marios Papasotiriou, Barbara M. Klinkhammer, Stephanie Zok, Ole Klaener, Gerald S. Braun, Maja T. Lindenmeyer, Clemens D. Cohen, Richard Bucala, Andre P. Tittel, Christian Kurts, Marcus J. Moeller, Juergen Floege, Tammo Ostendorf, Jürgen Bernhagen, Peter Boor
Journal: Journal of the American Society of Nephrology (2015)

Pathologic proliferation of mesangial and parietal epithelial cells (PECs) is a hallmark of various glomerulonephritides. Macrophage migration inhibitory factor (MIF) is a pleiotropic cytokine that mediates inflammation by engagement of a receptor complex involving the components CD74, CD44, CXCR2, and CXCR4. The proliferative effects of MIF may involve CD74 together with the coreceptor and PEC activation marker CD44. Herein, we analyzed the effects of local glomerular MIF/CD74/CD44 signaling in proliferative glomerulonephritides. MIF, CD74, and CD44 were upregulated in the glomeruli of patients and mice with proliferative glomerulonephritides. During disease, CD74 and CD44 were expressed de novo in PECs and colocalized in both PECs and mesangial cells. Stress stimuli induced MIF secretion from glomerular cells in vitro and in vivo, in particular from podocytes, and MIF stimulation induced proliferation of PECs and mesangial cells via CD74. In murine crescentic GN, Mif-deficient mice were almost completely protected from glomerular injury, the development of cellular crescents, and the activation and proliferation of PECs and mesangial cells, whereas wild-type mice were not. Bone marrow reconstitution studies showed that deficiency of both nonmyeloid and bone marrow-derived Mif reduced glomerular cell proliferation and injury. In contrast to wild-type mice, Cd74-deficient mice also were protected from glomerular injury and ensuing activation and proliferation of PECs and mesangial cells. Our data suggest a novel molecular mechanism and glomerular cell crosstalk by which local upregulation of MIF and its receptor complex CD74/CD44 mediate glomerular injury and pathologic proliferation in GN.
Oral physostigmine treatment of patients with Alzheimer's disease
Authors: R C Mohs, B M Davis, C A Johns, A A Mathé, B S Greenwald, T B Horvath, K L Davis
Journal: American Journal of Psychiatry (1985)

Twelve patients with Alzheimer's disease received 0.0, 0.5, 1.0, 1.5, and 2.0 mg of oral physostigmine every 2 hours for 3-5 days; symptoms after each dose were assessed with the Alzheimer's Disease Assessment Scale. Placebo and the dose associated with the least severe symptoms were then readministered for 3-5 days each. Of the 10 patients who completed the study, three showed clinically significant improvement on the highest physostigmine dose in both phases, four more were marginally improved in both phases, and three had inconsistent responses to physostigmine. Cortisol measures obtained during a sleep study suggest that patients whose symptoms improved on physostigmine were those in whom oral physostigmine enhanced central cholinergic activity.
Impact of Metformin on Advanced Pancreatic Cancer Survival: Too Little, Too Late?
Authors: Yu-Xiao Yang, Anil K. Rustgi
Journal: Clinical Cancer Research (2015)

Abstract Metformin offers no survival advantage in patients with metastatic pancreatic cancer. Despite promising experimental evidence suggesting an antitumor effect of metformin, its impact on the survival of advanced pancreatic cancer is likely very limited. Future studies may need to consider its role in early-stage pancreatic cancer. Clin Cancer Res; 22(5); 1031–3. ©2015 AACR. See related article by Reni et al., p. 1076
The Identification of Further Minimal Regions of Overlap in Chronic Lymphocytic Leukemia Using High-Resolution SNP Arrays
Authors: Samantha JL Knight, Ruth Clifford, Pauline Robbe, Sara DC Ramos, Adam Burns, Adele T Timbs, Reem Alsolami, Susanne Weller, Angela Hamblin, Joanne Mason, Melanie Oates, Michalis Titsias, Christopher Yau, Chris C Holmes, Andrew R Pettitt, Peter Hillmen, Jenny Taylor, Anna Shuh
Journal: Blood (2014)