tbuckley/cabot-search huggingface dataset:
Evolutionary Interrogation of Human Biology in Well-Annotated Genomic Framework of Rhesus Macaque
Authors: Shi-Jian Zhang, Chu-Jun Liu, Peng Yu, Xiaoming Zhong, Jia-Yu Chen, Xinzhuang Yang, Jiguang Peng, Shouyu Yan, Chenqu Wang, Xiaotong Zhu, Jingwei Xiong, Yong E. Zhang, Bertrand Chin-Ming Tan, Chuan-Yun Li
Journal: Molecular Biology and Evolution (2014)

With genome sequence and composition highly analogous to human, rhesus macaque represents a unique reference for evolutionary studies of human biology. Here, we developed a comprehensive genomic framework of rhesus macaque, the RhesusBase2, for evolutionary interrogation of human genes and the associated regulations. A total of 1,667 next-generation sequencing (NGS) data sets were processed, integrated, and evaluated, generating 51.2 million new functional annotation records. With extensive NGS annotations, RhesusBase2 refined the fine-scale structures in 30% of the macaque Ensembl transcripts, reporting an accurate, up-to-date set of macaque gene models. On the basis of these annotations and accurate macaque gene models, we further developed an NGS-oriented Molecular Evolution Gateway to access and visualize macaque annotations in reference to human orthologous genes and associated regulations (www.rhesusbase.org/molEvo). We highlighted the application of this well-annotated genomic framework in generating hypothetical link of human-biased regulations to human-specific traits, by using mechanistic characterization of the DIEXF gene as an example that provides novel clues to the understanding of digestive system reduction in human evolution. On a global scale, we also identified a catalog of 9,295 human-biased regulatory events, which may represent novel elements that have a substantial impact on shaping human transcriptome and possibly underpin recent human phenotypic evolution. Taken together, we provide an NGS data-driven, information-rich framework that will broadly benefit genomics research in general and serves as an important resource for in-depth evolutionary studies of human biology.
Coagulation Facilitates Tumor Cell Spreading in the Pulmonary Vasculature during Early Metastatic Colony Formation
Authors: Jae Hong Im, Weili Fu, Hui Wang, Sujata K. Bhatia, Daniel A. Hammer, M. Anna Kowalska, Ruth J. Muschel
Journal: Cancer Research (2004)

Abstract Coagulation has long been known to facilitate metastasis. To pinpoint the steps where coagulation might play a role in the metastasis, we used three-dimensional visualization of direct infusion of fluorescence labeled antibody to observe the interaction of tumor cells with platelets and fibrinogen in isolated lung preparations. Tumor cells arrested in the pulmonary vasculature were associated with a clot composed of both platelets and fibrin(ogen). Initially, the cells attached to the pulmonary vessels were rounded. Over the next 2 to 6 hours, they spread on the vessel surface. The associated clot was lysed coincident with tumor cell spreading. To assess the importance of clot formation, we inhibited coagulation with hirudin, a potent inhibitor of thrombin. The number of tumor cells initially arrested in the lung of hirudin-treated mice was essentially the same as in control mice. However, tumor cell spreading and subsequent retention of the tumor cells in the lung was markedly inhibited in the anticoagulated mice. These associations of the tumor cells with platelets were independent of tumor cell expression of P-selectin ligands. This work identifies tumor cell spreading onto the vascular surface as an important component of the metastatic cascade and implicates coagulation in this process.
Behavioral Counseling to Prevent Sexually Transmitted Infections: A Systematic Review for the U.S. Preventive Services Task Force
Authors: Jennifer S. Lin, Evelyn Whitlock, Elizabeth O'Connor, Vance Bauer
Journal: Annals of Internal Medicine (2008)

Background: Despite advances in prevention and treatment, sexually transmitted infections (STIs) remain an important cause of morbidity and mortality in the United States. Purpose: To systematically review the evidence for behavioral counseling interventions to prevent STIs in adolescents and adults (nonpregnant and pregnant). Data Sources: English-language articles in MEDLINE, PsycINFO, the Centers for Disease Control and Prevention's Prevention Synthesis Research Project database, and Cochrane databases (1988 through December 2007), supplemented with expert recommendations and the bibliographies of previous systematic reviews. Study Selection: Reviewers included 21 articles representing 15 fair- or good-quality randomized, controlled trials that evaluated behavioral counseling interventions feasible in primary care and 1 fair-quality and 1 good-quality controlled trial with study samples representative of primary care populations in English-speaking countries. Comparative effectiveness trials that did not include a true control group were excluded. Data Extraction: Investigators abstracted, critically appraised, and synthesized 21 articles that met inclusion criteria. Data Synthesis: Most evidence suggests a modest reduction in STIs at 12 months among high-risk adults receiving multiple intervention sessions and among sexually active adolescents. Evidence also suggested that these interventions increase adherence to treatment recommendations for women in STI clinics and general contraceptive use in male adolescents and decrease nonsexual risky behavior and pregnancy in sexually active female adolescents. No evidence of substantial behavioral or biological harms for risk reduction counseling was found. Limitation: Significant clinical heterogeneity in study populations, interventions, and measurement of outcomes limited the reviewers' ability to meta-analyze trial results and to suggest important intervention components. Conclusion: Good-quality evidence suggests that behavioral counseling interventions with multiple sessions conducted in STI clinics and primary care effectively reduces STI incidence in "at-risk" adult and adolescent populations. Additional trial evidence is needed for both lower-intensity behavioral counseling interventions and lower-risk patient populations.
Unbiased Metabolite Profiling Indicates That a Diminished Thymidine Pool Is the Underlying Mechanism of Colon Cancer Chemoprevention by Alpha-Difluoromethylornithine
Authors: Mavee Witherspoon, Qiuying Chen, Levy Kopelovich, Steven S. Gross, Steven M. Lipkin
Journal: Cancer Discovery (2013)

The ornithine decarboxylase inhibitor α-difluoromethylornithine (DFMO) is a highly effective chemopreventive agent for colorectal cancer thought to act via polyamine depletion. However, in DFMO-treated patients, mucosal polyamine levels do not directly correlate with colorectal cancer risk. Untargeted metabolite profiling was used to broadly survey DFMO actions on colon cancer cell metabolism. We found that DFMO treatment of Apc(Min) intestinal tumors and human colorectal cancer cells is associated with reduced levels of folate-dependent metabolites, including S-adenosylmethionine (SAM), thymidine pools, and related pathway intermediates. We hypothesized that unrestrained SAM consumption/regeneration constitutes a futile DFMO-triggered cascade that can steal tetrahydrofolate from thymidylate synthase and thereby diminish thymidine pools. In accord with this hypothesis, DFMO treatment altered the folate cofactor balance and thymidine supplementation prevented DFMO-elicited cytostasis without restoring polyamine levels. These findings suggest that thymidine metabolite pool insufficiency is a fundamental mechanism of DFMO cytostatic activity.
Childhood Sexual Abuse as a Risk Factor for Depression in Women: Psychosocial and Neurobiological Correlates
Authors: E L Weiss, J G Longhurst, C M Mazure
Journal: American Journal of Psychiatry (1999)

OBJECTIVE: Depression is twice as common in women as in men, but the reason for this sexual dimorphism is unknown. This article reviews recent studies of the role of childhood sexual abuse in the subsequent development of major depressive disorder, and the biological and psychosocial mechanisms by which early stressors may contribute to adult-onset depression in women. Particular attention is paid to investigations of the long-term effects of early stress on hypothalamic-pituitary-adrenal (HPA) axis function. METHOD: Studies were identified by means of computerized and manual searches; further references were obtained from the bibliographies of reviewed articles. RESULTS: Childhood sexual abuse is associated with adult-onset depression in both men and women, and occurrence of such abuse is more common in girls than in boys. There is evidence from both animal and human studies that early stressors produce long-term dysregulation of the HPA axis similar to that seen in depressed patients and that such dysregulation results in a differential response to stressors in adulthood. In addition, it appears that the HPA axis in females may be more susceptible to stress-induced dysregulation, which might contribute to an increased vulnerability to depression in adulthood. CONCLUSIONS: Childhood sexual abuse is an important early stressor that may predispose individuals to adult-onset depression by means of dysregulation of the HPA axis. Investigation of the mechanisms mediating the relationship between childhood sexual abuse and adult-onset depression, and the study of gender differences in exposure to this and other stressors, may improve our understanding of the etiology of depressive illness in general.
Penile ulcerations with foscarnet
Authors: S Fégueux, D Salmon, C Picard, C Sauvage, P Longuet, TH Desmoulins, G Moyle, S.E Barton, A Balestrini, M Nelson, M Youle, D.A Hawkins, B.G Gazzard, J.-O Lernestedt, A.C Chanas
Journal: The Lancet (1990)
Intravenous Coronary Angiography by Electron Beam Computed Tomography
Authors: Benno J. Rensing, Alfons Bongaerts, Robert-Jan van Geuns, Peter van Ooijen, Matthijs Oudkerk, Pim J. de Feyter
Journal: Circulation (1998)

-Noninvasive detection of coronary stenoses with electron beam CT (EBCT) after intravenous injection of contrast medium has recently emerged. We sought to determine the diagnostic accuracy of EBCT angiography in the clinical setting using conventional coronary angiography as the "gold standard."Thirty-seven patients (30 men) were investigated. After intravenous injection of 150 mL of contrast medium, 40 to 60 consecutive transaxial tomograms, covering the proximal and middle parts of the coronary arteries, were obtained with ECG triggering at end diastole during breath-holding. Three-dimensional reconstructions of the proximal and middle parts of the arteries were compared with the conventional angiograms. Of the 259 proximal and middle coronary segments, 211 (81%) were analyzable by EBCT. Of the left anterior descending coronary artery (LAD) segments, 95% were assessable. Right coronary artery (RCA) and left circumflex artery (LCx) segments were assessable in 66% and 76%, respectively. Overall sensitivity and specificity to detect a >50% diameter stenosis were 77% and 94%, respectively. This was 82% and 92% for the LAD, 60% and 97% for the RCA, and 83% and 89% for the LCx (all figures based on assessable lesions).Intravenous EBCT coronary angiography is a promising coronary imaging technique. The technique is not yet robust enough to be an alternative to conventional coronary angiography. It can detect and rule out significant coronary artery disease of the left main proximal and mid portions of the LAD with good accuracy.
Lesion Development and Response to Immunization Reveal a Complex Role for CD4 in Atherosclerosis
Authors: Xinghua Zhou, Anna-Karin L. Robertson, Mats Rudling, Paolo Parini, Göran K. Hansson
Journal: Circulation Research (2005)

Atherosclerosis is a complex disease, bearing many of the characteristics of a chronic inflammatory process. Both cellular and humoral immune responses may be involved in the disease development. Oxidized low-density lipoprotein (oxLDL) is suggested to be an autoantigen in atherosclerosis. A protective effect against atherosclerosis has been demonstrated in animals immunized with oxLDL. Such a protection is associated with elevation of T cell–dependent IgG antibodies against oxLDL. In addition, it has been shown that immunization with Freund adjuvant alone also confers protection against development of atherosclerosis. We therefore hypothesized that CD4+ T cells are critical in the development of atherosclerosis and that they are involved in protective immune reactions after immunization. The development of atherosclerosis was studied in apolipoprotein E knockout (apoE KO) mice and CD4/apoE double knockout (dKO) mice that were immunized with either oxLDL in Freund adjuvant or adjuvant alone, or left untreated. Our results show that (1) the absence of CD4+ cells in apoE KO mice leads to reduced atherosclerosis, indicating that CD4+ cells constitute a major proatherogenic cell population, and (2) the atheroprotective effect of LDL immunization does not depend on CD4+ cells, whereas (3) the atheroprotective effect of adjuvant injection is CD4-dependent. These findings demonstrate complex roles of immune cell-cell interactions in the regulation of the atherosclerotic process and point to several possible targets in the treatment and prevention of atherosclerosis.
Transient perturbation of endothelial integrity induced by natural antibodies and complement.
Authors: S Saadi, J L Platt
Journal: The Journal of Experimental Medicine (1995)

The barrier function of blood vessels is though to be regulated at least in part by endothelium. This concept is supported by the dramatic loss of barrier function occurring in the hyperacute rejection of vascularized grafts mediated by anti-endothelial cell (EC) antibodies and complement. In this process, the endothelium is not destroyed but instead loses the ability to retain blood cells and plasma proteins within capillaries. The noncytotoxic mechanism that allows this change in EC function has been unknown. Here we report that within 10 to 20 min of exposure to human xenoreactive natural antibodies and complement, porcine EC undergo alterations in cell shape and in the cytoskeleton that disrupt monolayer integrity and lead to formation of intercellular gaps. Gap formation is not associated with cell death but requires the complement complex C5b67. The gaps induced by anti-EC antibodies and complement are transient; gap closure requires formation of C5b-9 complexes on the cells and the rate of recovery depends on the release of cellular products into the medium. Preincubation of EC with dibutyryl cAMP (0.5 mM) prevents gap formation and disruption of the cytoskeleton caused by antibodies and complement. These results provide evidence that the integrity of endothelium is regulated by components of the complement system and suggest a mechanism that may explain the prominent loss of endothelial integrity seen in humoral immune responses.
Diagnosing tuberculosis with urine lipoarabinomannan: systematic review and meta-analysis
Authors: J. Minion, E. Leung, E. Talbot, K. Dheda, M. Pai, D. Menzies
Journal: European Respiratory Journal (2011)

Lipoarabinomannan (LAM) is a potential marker of active tuberculosis (TB). We performed a systematic review and meta-analysis regarding use of urinary LAM assays for diagnosing active TB. We systematically searched for published and unpublished studies that evaluated urinary LAM for active TB diagnosis. Extracted data were pooled using bivariate random effects models and hierarchical summary receiver operating characteristic curves. Heterogeneity was explored through subgroup analysis and meta-regression. Quality was assessed according to standardised QUADAS (Quality Assessment of Diagnostic Accuracy Studies) criteria. In seven studies that assessed test accuracy in microbiologically confirmed cases only, estimates of sensitivity ranged from 13% to 93%, while specificity ranged from 87% to 99%. In five studies that assessed accuracy in clinical and confirmed TB cases, sensitivity ranged from 8% to 80%, while specificity ranged from 88% to 99%. In five studies with results stratified by HIV status, sensitivity was 3–53% higher in HIV-positive than HIV-negative subgroups; sensitivity was highest with advanced immunosuppression. The LAM urinary assay has several characteristics that make it attractive for diagnosing active TB, but has suboptimal sensitivity for routine clinical use. Further studies are needed to evaluate the potential value of the LAM assay in individuals with advanced HIV or for diagnosis of paediatric TB.
Risk-taking, fear, dominance, and testosterone
Authors: John Archer
Journal: Behavioral and Brain Sciences (1999)

Campbell's analysis of the evolution of human sex differences to include selection pressures on the female is generally welcomed. This commentary raises some specific issues about the evidence cited: the impact of paternal death on survival prospects; a possible mechanism underlying a sex difference in fear; the selective advantage of dominance hierarchies; and the absence of evidence that testosterone causes human aggression.
What predicts poor collection of medication among children with asthma? A case-control study
Authors: L. Irvine, I.K. Crombie, E.M. Alder, R.G. Neville, R.A. Clark
Journal: European Respiratory Journal (2002)

Compliance with asthma medication is recognised to be a problem. Acquisition of medication is the first step towards compliance. Factors predicting poor collection of prophylactic medication were investigated. A case/control study was conducted. Cases were children who had had at least two consultations for poorly controlled asthma in 1 yr and collected prescriptions of prophylactic medication irregularly. Controls were children whose prescriptions were collected as instructed. Levels of knowledge about asthma and asthma medication were high in both groups. Parents of cases were more likely to perceive their child's asthma to be moderate or severe and more likely to report that their child's asthma was not well controlled. They reported more night-time symptoms, exercise symptoms and school absence. Parents of cases were less likely to report that administering inhalers was part of the evening routine. They were less likely to perceive their child's prophylactic medication to be very effective and more reluctant to administer prophylactic medication. Some parents may decide to undertreat their children, although lack of organised routine may contribute to poor compliance. Parents need guidance on interpreting symptoms and support in establishing routines for the administration of medication.
The Evolution of Polymorphic Compatibility Molecules
Authors: RJ De Boer
Journal: Molecular Biology and Evolution (1995)

Several primitive colonial organisms distinguish self from nonself by means of polymorphic compatibility molecules
bearing similarity to the major histocompatibility complex (MHC). The evolution of such polymorphisms is
generally explained in terms of resistance to parasites. Ignoring parasites, I develop two mathematical models. One
model is inspired by slime mold aggregation. The other is a caricature. The results show that parasites are not
required to explain polymorphisms. The fact that allorecognition allows organisms to maintain their “genetic
identity” (e.g., to preserve evolved adaptations) suffices for the evolution of polymorphisms. The degree of polymorphism
that ultimately evolves is equal to the diversity of phenotypes in the population. In these models I
consider “cells” growing in particular environments. The “genotype” of a cell codes for an “ecological preference,”
which determines the growth rate of the cell in the environment, and for a “compatibility molecule.” Cells expressing
the same compatibility molecule form one “colony.” Thus, colonies may be chime& with respect to the ecological
preferences. The reproduction rate of each cell in a colony is weighted by the colony’s composition of ecological
preferences. These conditions turn out to be sufficient for the evolution of polymorphic compatibility molecules.
Differential expressions of CD25 or CD71 on CD4+ and/or CD8+ tumor cells from a patient with adult T‐cell leukemia/lymphoma: Three color flowcytometric analysis of peripheral blood and lymph node
Authors: Fumio Omata, Yukinobu Ichikawa, Yoshitaka Kushibiki, Hiroaki Shimizu, Miyoko Yoshida, Mitsumoto Komatsuda, Shigeru Arimori
Journal: American Journal of Hematology (1992)
Under Pressure: Cellular and Molecular Responses During Glaucoma, a Common Neurodegeneration with Axonopathy
Authors: Robert W. Nickells, Gareth R. Howell, Ileana Soto, Simon W.M. John
Journal: Annual Review of Neuroscience (2012)

Glaucoma is a complex neurodegenerative disorder that is expected to affect 80 million people by the end of this decade. Retinal ganglion cells (RGCs) are the most affected cell type and progressively degenerate over the course of the disease. RGC axons exit the eye and enter the optic nerve by passing through the optic nerve head (ONH). The ONH is an important site of initial damage in glaucoma. Higher intraocular pressure (IOP) is an important risk factor for glaucoma, but the molecular links between elevated IOP and axon damage in the ONH are poorly defined. In this review and focusing primarily on the ONH, we discuss recent studies that have contributed to understanding the etiology and pathogenesis of glaucoma. We also identify areas that require further investigation and focus on mechanisms identified in other neurodegenerations that may contribute to RGC dysfunction and demise in glaucoma.
Knee kinematics and joint moments during gait following anterior cruciate ligament reconstruction: a systematic review and meta-analysis
Authors: Harvi F Hart, Adam G Culvenor, Natalie J Collins, David C Ackland, Sallie M Cowan, Zuzana Machotka, Kay M Crossley
Journal: British Journal of Sports Medicine (2015)

Abnormal gait after anterior cruciate ligament reconstruction (ACLR) may contribute to development and/or progression of knee osteoarthritis.To conduct a systematic review and meta-analysis of knee kinematics and joint moments during walking after ACLR.We searched seven electronic databases and reference lists of relevant papers, for cross-sectional, human-based observational studies comparing knee joint kinematics and moments during level walking in individuals with ACLR, with the uninjured contralateral knee or healthy individuals as a control. Two independent reviewers appraised methodological quality (modified Downs and Black scale). Where possible, data were pooled by time post-ACLR (RevMan), otherwise narrative synthesis was undertaken.Thirty-four studies were included. Meta-analysis revealed significant sagittal plane deficits in ACLR knees. We found greater knee flexion angles (standardised mean difference: 1.06; 95% CI 0.39 to 1.74) and joint moments (1.61; 0.87 to 2.35) <6 months post-ACLR, compared to healthy controls. However, lower peak knee flexion angles were identified 1-3 years (-2.21; -3.16 to -1.26) and ≥3 years post-ACLR (-1.38, -2.14 to -0.62), and lower knee flexion moment 6-12 months post-ACLR (-0.76; -1.40 to -0.12). Pooled data provided strong evidence of no difference in peak knee adduction moment >3 years after ACLR (vs healthy controls) (0.09; -0.63 to 0.81). No transverse plane conclusions could be drawn.Sagittal plane biomechanics, rather than the knee adduction moment, appear to be more relevant post-ACLR. Better understanding of sagittal plane biomechanics is necessary for optimal post-operative recovery, and to potentially prevent early onset and progression of knee OA after ACLR.PROSPERO systematic review protocol registration number CRD4201400882 2.