tbuckley/cabot-search huggingface dataset:
Estimates of Global and Regional Premature Cardiovascular Mortality in 2025
Authors: Gregory A. Roth, Grant Nguyen, Mohammad H. Forouzanfar, Ali H. Mokdad, Mohsen Naghavi, Christopher J.L. Murray
Journal: Circulation (2015)

United Nations member states have agreed to reduce premature cardiovascular disease (CVD) mortality 25% by 2025. Global CVD risk factor targets have been recommended. We produced estimates to show how selected risk factor reduction would affect CVD mortality for different regions and countries.We used mortality, risk factor, and relative risk data from the Global Burden of Disease, Risk Factors, and Injuries (GBD) 2013 study to project CVD mortality for 188 countries up to the year 2025. We disaggregated observed CVD mortality in 1990 and 2013 into deaths attributable and unattributable to hypertension, tobacco smoking, diabetes mellitus, and obesity using an age- and sex-specific population-attributable fraction. Risk factors were projected to 2025 assuming that current trends continue. Counterfactual scenarios were then constructed reflecting CVD premature mortality if United Nations risk factor targets are achieved in the year 2025, adjusting for joint effects of risk factors. We estimate 7.8 million premature CVD deaths in 2025 if current risk factor trends continue. Premature CVD deaths would be reduced to 5.7 million if these risk factors targets are achieved as a result of a 26% reduction for men and a 23% reduction for women in the global risk of premature CVD death. Globally, decreasing the prevalence of hypertension accounted for the largest risk reduction, followed by a reduction in tobacco smoking for men and obesity for women, but these results varied by region. The impact of meeting all risk factor targets on CVD mortality varied widely by region and sex.The United Nations target of a 25% reduction in premature CVD mortality by the year 2025 appears achievable for some countries, but more aggressive risk factor targets may be required if all regions are to reach this goal. Without these reductions in CVD risk factors, many countries will see no change or even an increase in premature CVD mortality.
Human antibodies induce arthritis in mice deficient in the low-affinity inhibitory IgG receptor FcγRIIB
Authors: Stefka B. Petkova, Konstantin N. Konstantinov, Thomas J. Sproule, Bonnie L. Lyons, Moheeb Al Awwami, Derry C. Roopenian
Journal: The Journal of Experimental Medicine (2006)

Rheumatoid arthritis (RA) is a complex autoimmune disease with a poorly understood pathogenesis. The disease is associated with polyclonal B cell activation and the production of autoantibodies (autoAbs), but there is a longstanding controversy as to whether such Abs contribute to, or are secondary to, the pathogenesis of RA. To address the potential pathogenicity of human RA–associated Abs, we developed a passive transfer model involving mice deficient in the low-affinity inhibitory Fc receptor, FcγRIIB. We report that plasma or serum from patients with active RA can induce inflammation and histological lesions in FcγRIIB−/− mice consistent with arthritis, and that this pathogenic activity is caused by the immunoglobulin G–rich fraction. Our results suggest that humoral autoimmunity can contribute directly to autoimmune arthritis, and that FcγRIIB−/− mice are a promising model to evaluate the arthritogenic potential of human autoAbs.
Disrupted lymphocyte homeostasis in hepatitis‐associated acquired aplastic anemia is associated with short telomeres
Authors: Daria V. Babushok, Anne‐Laure Grignon, Yimei Li, Jamie Atienza, Hongbo M. Xie, Ho‐Sun Lam, Helge Hartung, Monica Bessler, Timothy S. Olson
Journal: American Journal of Hematology (2015)

Hepatitis-associated aplastic anemia (HAA) is a variant of acquired aplastic anemia (AA) in which immune-mediated bone marrow failure (BMF) develops following an acute episode of seronegative hepatitis. Dyskeratosis congenita (DC) is an inherited BMF syndrome characterized by the presence of short telomeres, mucocutaneous abnormalities, and cancer predisposition. While both conditions may cause BMF and hepatic impairment, therapeutic approaches are distinct, making it imperative to establish the correct diagnosis. In clinical practice, lymphocyte telomere lengths (TL) are used as a first-line screen to rule out inherited telomeropathies before initiating treatment for AA. To evaluate the reliability of TL in the HAA population, we performed a retrospective analysis of TL in 10 consecutively enrolled HAA patients compared to 19 patients with idiopathic AA (IAA). HAA patients had significantly shorter telomeres than IAA patients (P = 0.009), including four patients with TL at or below the 1st percentile for age-matched controls. HAA patients had no clinical features of DC and did not carry disease-causing mutations in known genes associated with inherited telomere disorders. Instead, short TLs were significantly correlated with severe lymphopenia and skewed lymphocyte subsets, features characteristic of HAA. Our results indicate the importance of caution in the interpretation of TL measurements in HAA, because, in this patient population, short telomeres have limited specificity.
Modulation of 5-fluorouracil with methotrexate and low-dose N-(phosphon acetyl)-L-aspartate (PALA) is inactive in advanced pancreatic carcinoma
Authors: A. Harstrick, C.H. Köhne, W. Hiddemann, P. Preusser, D. Strumberg, T. Berns, S. Seeber, H. Wilke, H.J. Schmoll
Journal: Annals of Oncology (1997)
Performance of the Breast Cancer Risk Assessment Tool Among Women Age 75 Years and Older
Authors: Mara A. Schonberg, Vicky W. Li, A. Heather Eliassen, Roger B. Davis, Andrea Z. LaCroix, Ellen P. McCarthy, Bernard A. Rosner, Rowan T. Chlebowski, Thomas E. Rohan, Susan E. Hankinson, Edward R. Marcantonio, Long H. Ngo
Journal: JNCI Journal of the National Cancer Institute (2015)

The Breast Cancer Risk Assessment Tool (BCRAT, “Gail model”) is commonly used for breast cancer prediction; however, it has not been validated for women age 75 years and older. We used Nurses’ Health Study (NHS) data beginning in 2004 and Women’s Health Initiative (WHI) data beginning in 2005 to compare BCRAT’s performance among women age 75 years and older with that in women age 55 to 74 years in predicting five-year breast cancer incidence. BCRAT risk factors include: age, race/ethnicity, age at menarche, age at first birth, family history, history of benign breast biopsy, and atypia. We examined BCRAT’s calibration by age by comparing expected/observed (E/O) ratios of breast cancer incidence. We examined discrimination by computing c-statistics for the model by age. All statistical tests were two-sided. Seventy-three thousand seventy-two NHS and 97 081 WHI women participated. NHS participants were more likely to be non-Hispanic white (96.2% vs 84.7% in WHI, P < .001) and were less likely to develop breast cancer (1.8% vs 2.0%, P = .02). E/O ratios by age in NHS were 1.16 (95% confidence interval [CI] = 1.09 to 1.23, age 57–74 years) and 1.31 (95% CI = 1.18 to 1.45, age ≥ 75 years, P = .02), and in WHI 1.03 (95% CI = 0.97 to 1.09, age 55–74 years) and 1.10 (95% CI = 1.00 to 1.21, age ≥ 75 years, P = .21). E/O ratio 95% confidence intervals crossed one among women age 75 years and older when samples were limited to women who underwent mammography and were without significant illness. C-statistics ranged between 0.56 and 0.58 in both cohorts regardless of age. BCRAT accurately predicted breast cancer for women age 75 years and older who underwent mammography and were without significant illness but had modest discrimination. Models that consider individual competing risks of non–breast cancer death may improve breast cancer risk prediction for older women.
Kallistatin protects against diabetic nephropathy in db/db mice by suppressing AGE-RAGE-induced oxidative stress
Authors: Wai Han Yiu, Dickson W.L. Wong, Hao Jia Wu, Rui Xi Li, Irene Yam, Loretta Y.Y. Chan, Joseph C.K. Leung, Hui Yao Lan, Kar Neng Lai, Sydney C.W. Tang
Journal: Kidney International (2015)
Oocyte activation deficiency: a role for an oocyte contribution?
Authors: Marc Yeste, Celine Jones, Siti Nornadhirah Amdani, Sheena Patel, Kevin Coward
Journal: Human Reproduction Update (2015)

Infertility affects between 10 and 16% of couples worldwide. Twenty to 30% of cases of infertility are due to a male factor, 20–35% to a female factor, and 25–40% are due to both male and female factors. In ∼10–25% of cases, the precise underlying cause remains unclear. IVF or ICSI followed by embryo transfer can be very appropriate treatment options in cases of female tubal damage, ovulatory failure or male-factor infertility. While the use of IVF has been reported to be suitable for many infertile couples, normal IVF cycles can fail in some cases. While ICSI can represent a powerful alternative in cases of IVF failure, complete fertilization failure can still occur in 1–5% of ICSI cycles. This can be due to a variety of factors and while commonly attributed to deficiency of sperm factors, it is very likely that abnormalities in crucial oocyte factors could also play a key role. A critical literature review using PubMed was performed between April 2014 and July 2015 targeting studies concerning sperm and oocyte factors that could account for oocyte activation deficiency, and including studies of in vitro oocyte maturation in human oocytes, and animal models. Accumulating evidence indicates that phospholipase C zeta (PLCζ) is the sperm oocyte activation factor, although recent studies claim that another sperm protein known as post-acrosomal WWP-binding domain protein could also play a significant role in the activation of oocytes. The present review discusses our current understanding of these two proteins but emphasizes that defects in the molecular machinery within the oocyte that interacts with such sperm proteins may also represent an underlying cause of fertilization failure and infertility, especially in cases where there is no obvious indication for sperm deficiency. Abnormalities in such mechanisms are highly likely to exert influence over the pulsatile release of calcium within the ooplasm, the critical signal that controls oocyte activation events. These molecular targets within the oocyte are rarely, if ever, considered clinically. We therefore recommend that future diagnostic assays should be developed to consider the inositol triphosphate receptor, protein kinase C, proteins associated with stored operated calcium entry calcium/calmodulin-dependent protein kinase II and mitogen-activated protein kinase. Development of such assays would represent a significant step forward in the diagnosis of oocyte activation deficiency and may identify a series of potential therapeutic targets. The present review provides a general overview of how a combination of sperm and oocyte factors can underlie oocyte activation deficiency, but pays particular attention to the less appreciated role of the oocyte. Enhanced research within this realm is much warranted and may establish new approaches for the diagnosis and treatment of infertility.
Effects of carriage and expression of the Tn10 tetracycline-resistance operon on the fitness of Escherichia coli K12.
Authors: T N Nguyen, Q G Phan, L P Duong, K P Bertrand, R E Lenski
Journal: Molecular Biology and Evolution (1989)

We have been examining the consequences of alternative modes of regulation of plasmid-borne, Tn10-encoded tetracycline resistance for the fitness of Escherichia coli. In a tetracycline-free environment, we measured the effects on fitness that were caused by (1) maximally induced expression of the resistance operon, (2) low-level constitutive expression of the resistance protein, (3) residual expression of the repressed resistance operon, (4) carriage of the resistance operon, (5) the remainder of the plasmid genome, and (6) hyperexpression of the repressor protein. We observed large reductions in fitness that were associated with induction and with constitutive expression of the tetracycline-resistance protein, but there was no discernible effect of hyperexpression of the repressor protein. We also observed a small reduction in fitness associated with the remainder of the plasmid genome. However, any reductions in fitness that were caused by residual expression and by carriage of the repressed operon were not more than 0.3%. We conclude that tight gene regulation has eliminated antagonistic pleiotropic effects of the resistance gene on fitness, so that possession of an inducible Tn10-encoded tetracycline-resistance operon imposes essentially no burden in the absence of antibiotic.
A Phase III Trial Comparing Folfirinox Versus Gemcitabine for Metastatic Pancreatic Cancer
Authors: M.K. Singhal, A. Kapoor, P.K. Bagri, S. Narayan, D. Singh, R.K. Nirban, G. Singh, S. Maharia, P. Kumari, S.L. Jakhar, S. Beniwal, N. Sharma, K. Harsh, H.S. Kumar, A. Sharma, M. Bardia
Journal: Annals of Oncology (2014)
ADCK4-Associated Glomerulopathy Causes Adolescence-Onset FSGS
Authors: Emine Korkmaz, Beata S. Lipska-Ziętkiewicz, Olivia Boyer, Olivier Gribouval, Cecile Fourrage, Mansoureh Tabatabaei, Sven Schnaidt, Safak Gucer, Figen Kaymaz, Mustafa Arici, Ayhan Dinckan, Sevgi Mir, Aysun K. Bayazit, Sevinc Emre, Ayse Balat, Lesley Rees, Rukshana Shroff, Carsten Bergmann, Chebl Mourani, Corinne Antignac, Fatih Ozaltin, Franz Schaefer
Journal: Journal of the American Society of Nephrology (2015)

Hereditary defects of coenzyme Q10 biosynthesis cause steroid-resistant nephrotic syndrome (SRNS) as part of multiorgan involvement but may also contribute to isolated SRNS. Here, we report 26 patients from 12 families with recessive mutations in ADCK4. Mutation detection rate was 1.9% among 534 consecutively screened cases. Patients with ADCK4 mutations showed a largely renal-limited phenotype, with three subjects exhibiting occasional seizures, one subject exhibiting mild mental retardation, and one subject exhibiting retinitis pigmentosa. ADCK4 nephropathy presented during adolescence (median age, 14.1 years) with nephrotic-range proteinuria in 44% of patients and advanced CKD in 46% of patients at time of diagnosis. Renal biopsy specimens uniformly showed FSGS. Whereas 47% and 36% of patients with mutations in WT1 and NPHS2, respectively, progressed to ESRD before 10 years of age, ESRD occurred almost exclusively in the second decade of life in ADCK4 nephropathy. However, CKD progressed much faster during adolescence in ADCK4 than in WT1 and NPHS2 nephropathy, resulting in similar cumulative ESRD rates (>85% for each disorder) in the third decade of life. In conclusion, ADCK4-related glomerulopathy is an important novel differential diagnosis in adolescents with SRNS/FSGS and/or CKD of unknown origin.
Autologous dendritic cell immunotherapy (DCVAC/PCa) added to docetaxel chemotherapy in a Phase III trial (viable) in men with advanced (mCRPC) prostate cancer
Authors: Tomasz M Beer, Nicholas Vogelzang, Jiřina Bartůňková, Kurt Miller, William Oh, Stephane Oudard, Hardev Pandha, A Oliver Sartor, Radek Špíšek, Timothy O Toole, Niels G Borgstein, Winald R Gerritsen
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts Prostate cancer (PCa) is the second most common cancer, and the fifth leading cause of cancer related death among men worldwide. Immunotherapy designed to induce tumor cell specific immune responses capable of destroying tumor cells has emerged as a promising treatment modality in
Is 100KF an Isoform of Hemopexin? Immunochemical Characterization of the Vasoactive Plasma Factor 100KF
Authors: PO KAM CHEUNG, BEN STULP, STEPHAN IMMENSCHUH, THEO BORGHUIS, JULIUS F. W. BALLER, WINSTON W. BAKKER
Journal: Journal of the American Society of Nephrology (1999)

Abstract. The human vasoactive plasma factor 100KF has been proposed to play a role in minimal change disease in relapse. Since preliminary data suggested similarity between 100KF and the human plasma glycoprotein hemopexin (Hx), this study was conducted to compare 100KF with purified Hx for sequence homology, immunostaining properties in Western and dot-blot assays, ability to affect glomerular ecto-ATPase and glomerular polyanions in vitro , as well as their glomerular permeability increasing effect following alternate perfusion into the rat kidney ex vivo . 100KF was purified from normal pooled plasma according to standard chromatographic techniques, and from the same batch Hx was prepared using affinity chromatography. A second batch of Hx was prepared directly from human serum according to a standard protocol. (For comparison, additional Hx samples obtained from other centers were also included in the study.) The results show: ( 1 ) 100% homology of 100KF with plasma Hx after internal sequence analysis; ( 2 ) positive staining of the eluate with both monoclonal and polyclonal anti-Hx IgG as well as anti-100KF IgG in dot-blot assays, and similar bands on Western blotting using the same antibodies; ( 3 ) affection of glomerular polyanions and glomerular ecto-ATPase after incubation of kidney tissue with either 100KF or Hx (1.5 respectively 1.0 mg/ml; 1.0 h, 37°C), as detected by computerized histochemical quantification; and ( 4 ) significant enhancement of urinary protein leakage after Hx perfusion followed by diluted rat serum into the rat kidney ex vivo (Hx: 210.65 ± 49.79 μg protein leakage per min versus heat-inactivated Hx control: 112.2 ± 49.18 μg per min [both n = 6]). From these data and from the observation that both Hx and 100KF activity can be inhibited by serine protease inhibitors but not by broad spectrum collagenase inhibitors, it is concluded that Hx may be closely related or identical to the active moiety of 100KF.
“Editing” Genes: A Case Study About How Language Matters in Bioethics
Authors: Meaghan O'Keefe, Sarah Perrault, Jodi Halpern, Lisa Ikemoto, Mark Yarborough
Journal: The American Journal of Bioethics (2015)

Metaphors used to describe new technologies mediate public understanding of the innovations. Analyzing the linguistic, rhetorical, and affective aspects of these metaphors opens the range of issues available for bioethical scrutiny and increases public accountability. This article shows how such a multidisciplinary approach can be useful by looking at a set of texts about one issue, the use of a newly developed technique for genetic modification, CRISPRcas9.
Surveillance de la résistance antimicrobienne au Danemark
Authors: D. L. Monnet, H. D. Hemborg, S. R Andersen, C Schöller, T. L. Sørensen, F Bager
Journal: Eurosurveillance (2000)

Selon les derniers resultats du programme DANMAP (Programme integre danois de surveillance et de recherche sur la resistance aux agents antimicrobiens), les niveaux de resistance chez Salmonella enterica sont faibles au Danemark. Quant a la resistance chez les souches d'Escherichia coli pathogenes pour les animaux, elle devrait etre consideree comme un reservoir de resistance, plutot que comme une menace pour la sante publique. Par ailleurs, les niveaux de resistance chez les souches cliniques d’E. coli sont coherents avec les profils d’utilisation des antibiotiques dans le pays. La resistance reste rare chez Staphylococcus aureus et Streptococcus pneumoniae. Cependant, l’emergence recente de souches de S. pneumoniae resistantes a la penicilline et a l’erythromycine est inquietante. Enfin, la surveillance de la resistance des bacteries commensales chez les animaux destines a la consommation et dans l’alimentation montrent que les mesures telles que l’interdiction de l’utilisation des antibiotiques comme promoteurs de croissance chez les animaux d’elevage, ont un effet positif sur la resistance.
Selective neutrality of glucose-6-phosphate dehydrogenase allozymes in Escherichia coli.
Authors: D E Dykhuizen, J de Framond, D L Hartl
Journal: Molecular Biology and Evolution (1984)

Six naturally occurring alleles representing four electromorphs of the enzyme glucose-6-phosphate dehydrogenase were transferred by P1-mediated transduction from natural isolates of Escherichia coli into the genetic background of E. coli K12 and were studied in pairwise competition in chemostats limited for glucose in order to estimate differences in growth rate associated with the alleles. Although the level of resolution of such experiments is a growth rate differential of approximately 0.002 h-1, no significant differences among the strains were found. Studies of apparent Km and Vmax in crude enzyme extracts of the strains also failed to reveal any significant differences among the electromorphs. These results support the view that the alleles are selectively neutral or nearly neutral under these conditions.
Designer invariants for large phylogenies.
Authors: D Sankoff
Journal: Molecular Biology and Evolution (1990)

The Cavender-Felsenstein edge-length invariants for binary characters on 4-trees provide the starting point for the development of "customized" invariants for evaluating and comparing phylogenetic hypotheses. The binary character invariants may be generalized to k-valued characters without losing the quadratic nature of the invariants as functions of the theoretical frequencies f(UVXY) of observable character configurations (U at organism 1, V at 2, etc.). The key to the approach is that certain sets of these configurations constitute events which are probabilistically independent from other such sets, under the symmetric Markov change models studied. By introducing more complex sets of configurations, we find the quadratic invariants for 5-trees in the binary model and for individual edges in 6-trees or, indeed, in any size tree. The same technique allows us to formulate invariants for entire trees, but these are cubic functions for 6-trees and are higher-degree polynomials for larger trees. With k-valued characters and, especially, with large trees, the types of configuration sets (events) used in the simpler examples are too rare (i.e., their predicted frequencies are too low) to be useful, and the construction of meaningful pairs of independent events becomes an important and nontrivial task in designing invariants suited to testing specific hypotheses. In a very natural way, this approach fits in with well-known statistical methodology for contingency tables. We explore use of events such as "only transitions occur for character i (i.e., position i in a nucleic acid sequence) in subtree a" in analyzing a set of data on ribosomal RNA in the context of the controversy over the origins of archaebacteria, eubacteria, and eukaryotes.
Controlling Shear Stress in 3D Bioprinting is a Key Factor to Balance Printing Resolution and Stem Cell Integrity
Authors: Andreas Blaeser, Daniela Filipa Duarte Campos, Uta Puster, Walter Richtering, Molly M. Stevens, Horst Fischer
Journal: Advanced Healthcare Materials (2015)

A microvalve-based bioprinting system for the manufacturing of high-resolution, multimaterial 3D-structures is reported. Applying a straightforward fluid-dynamics model, the shear stress at the nozzle site can precisely be controlled. Using this system, a broad study on how cell viability and proliferation potential are affected by different levels of shear stress is conducted. Complex, multimaterial 3D structures are printed with high resolution. This work pioneers the investigation of shear stress-induced cell damage in 3D bioprinting and might help to comprehend and improve the outcome of cell-printing studies in the future.
Clinical efficacy and management of monoclonal antibodies targeting CD38 and SLAMF7 in multiple myeloma
Authors: Niels W. C. J. van de Donk, Philippe Moreau, Torben Plesner, Antonio Palumbo, Francesca Gay, Jacob P. Laubach, Fabio Malavasi, Hervé Avet-Loiseau, Maria-Victoria Mateos, Pieter Sonneveld, Henk M. Lokhorst, Paul G. Richardson
Journal: Blood (2015)
t(11;22) and Other Chromosomal Rearrangements in Ewing's Sarcoma&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: E C Douglass, M Valentine, A A Green, F A Hayes, E I Thompson
Journal: JNCI Journal of the National Cancer Institute (1986)

Abnormal karyotypes from 13 human cases of Ewing's sarcoma are reported in this paper. The t(11;22) was seen in 9 cases, with 2 additional cases containing only a del(22). Other abnormalities included trisomy of 1q, translocations to 19p13, deletions of 3p and 6q, and homogeneously staining regions.