tbuckley/cabot-search huggingface dataset:
Comparative genomic analysis of C4 photosynthetic pathway evolution in grasses
Authors: Xiyin Wang, Udo Gowik, Haibao Tang, John E Bowers, Peter Westhoff, Andrew H Paterson
Journal: Genome biology (2009)

Abstract Background Sorghum is the first C4 plant and the second grass with a full genome sequence available. This makes it possible to perform a whole-genome-level exploration of C4 pathway evolution by comparing key photosynthetic enzyme genes in sorghum, maize (C4) and rice (C3), and to investigate a long-standing hypothesis that a reservoir of duplicated genes is a prerequisite for the evolution of C4 photosynthesis from a C3 progenitor. Results We show that both whole-genome and individual gene duplication have contributed to the evolution of C4 photosynthesis. The C4 gene isoforms show differential duplicability, with some C4 genes being recruited from whole genome duplication duplicates by multiple modes of functional innovation. The sorghum and maize carbonic anhydrase genes display a novel mode of new gene formation, with recursive tandem duplication and gene fusion accompanied by adaptive evolution to produce C4 genes with one to three functional units. Other C4 enzymes in sorghum and maize also show evidence of adaptive evolution, though differing in level and mode. Intriguingly, a phosphoenolpyruvate carboxylase gene in the C3 plant rice has also been evolving rapidly and shows evidence of adaptive evolution, although lacking key mutations that are characteristic of C4 metabolism. We also found evidence that both gene redundancy and alternative splicing may have sheltered the evolution of new function. Conclusions Gene duplication followed by functional innovation is common to evolution of most but not all C4 genes. The apparently long time-lag between the availability of duplicates for recruitment into C4 and the appearance of C4 grasses, together with the heterogeneity of origins of C4 genes, suggests that there may have been a long transition process before the establishment of C4 photosynthesis.
Antihypertensive Medication and Renal Allograft Failure
Authors: JONATHAN M. SOROF, E. KENNETH SULLIVAN, AMIR TEJANI, RONALD J. PORTMAN
Journal: Journal of the American Society of Nephrology (1999)

Abstract. Hypertension after renal transplantation occurs commonly and, in adults, is associated with decreased graft survival. The North American Pediatric Renal Transplant Cooperative Study database was analyzed to determine: ( 1 ) the percent use of antihypertensive (anti-HTN) medication based on donor type, race, age, and acute rejection status; and ( 2 ) whether use of anti-HTN medication is associated with higher rates of subsequent graft failure. Data regarding anti-HTN medication use was available in 5251 renal allografts (4821 patients) with &gt;30 d graft function. Posttransplant follow-up data were collected at 30 d, 6 mo, 12 mo, and then annually for 5 yr. At each follow-up, patients were selected for further analysis if the graft was functioning at that visit and subsequent follow-up data were available. Overall, anti-HTN medication use was 79% on day 30 and 58% at 5 yr. At each follow-up, anti-HTN medication use was higher ( P &lt; 0.01) for cadaveric donor versus living related donor, blacks versus whites, age &gt;12 versus &lt;12 yr, and ≥1 versus 0 acute rejection episodes. Anti-HTN medication use at each annual follow-up was associated with significantly higher rates of subsequent graft failure. Multiple regression analysis controlling for all factors associated with increased use of anti-HTN medications revealed a relative risk of graft failure for use of anti-HTN medication of greater than 1.4 ( P &lt; 0.001). In recipients of cadaveric allografts, only acute rejection status predicted subsequent graft failure more strongly than use of anti-HTN medications. These data suggest that hypertension after renal transplantation in children, as evidenced by use of anti-HTN medications, is associated with increased rates of subsequent graft failure.
Development of postnatal lung function in very low birth weight infants with or without BPD
Authors: Charles Roehr, Silke Wilitzki, Hans Proquitté, Christoph Bührer, Gerd Schmalisch
Journal: European Respiratory Journal (2012)

Background: Very low birth weight (VLBW) infants (  Patients and methods: Sequentially lung function tests (LFT) were performed at 50, 70 and 100 weeks postmenstrual age in 55 VLBW infants (29 with BPD (O2 supplementation at 36 weeks gestational age) and 26 VLBW infants without BPD (controls)). Mean gestational age (26 vs 29 weeks), birth weight (815 g vs 1125 g), and rates of mechanical ventilation ≥7d (55% vs 8%) differed significantly between BPD and controls.  Main results: Body weight and length were persistently lower in BPD infants, as compared to controls, no significant differences were seen for respiratory rate, respiratory and airway resistance, functional residual capacity (FRC), maximal expiratory flow at FRC and blood gas values. Tidal volume, minute ventilation, respiratory compliance and FRC determined by SF6 multiple breath washout were significantly lower in BPD infants compared to controls, but the differences vanished after normalization to body weight.  Conclusions: While somatic growth and some lung function parameter were delayed in BPD infants, their lung function appeared to develop along trajectories of non-BPD infants when actual body weight is being considered. Longitudinal LFT of preterm infants after discharge may help to identify BPD infants at risk of incomplete recovery of respiratory function, which can lead to respiratory problems later on.
Effect of Mild Exercise Training on Glucose Effectiveness in Healthy Men
Authors: Yuichiro Nishida, Yasuki Higaki, Kumpei Tokuyama, Kanta Fujimi, Akira Kiyonaga, Munehiro Shindo, Yuzo Sato, Hiroaki Tanaka
Journal: Diabetes Care (2001)

OBJECTIVE—To detect whether mild exercise training improves glucose effectiveness (SG), which is the ability of hyperglycemia to promote glucose disposal at basal insulin, in healthy men. RESEARCH DESIGN AND METHODS—Eight healthy men (18–25 years of age) underwent ergometer training at lactate threshold (LT) intensity for 60 min/day for 5 days/week for 6 weeks. An insulin-modified intravenous glucose tolerance test was performed before as well as at 16 h and 1 week after the last training session. SG and insulin sensitivity (SI) were estimated using a minimal-model approach. RESULTS—After the exercise training, Vo2max and Vo2 at LT increased by 5 and 34%, respectively (P &amp;lt; 0.05). The mild exercise training improves SG measured 16 h after the last training session, from 0.018 ± 0.002 to 0.024 ± 0.001 min−1 (P &amp;lt; 0.05). The elevated SG after exercise training tends to be maintained regardless of detraining for 1 week (0.023 ± 0.002 min−1, P = 0.09). SI measured at 16 h after the last training session significantly increased (pre-exercise training, 13.9 ± 2.2; 16 h, 18.3 ± 2.4, ×10−5 · min−1 · pmol/l−1, P &amp;lt; 0.05) and still remained elevated 1 week after stopping the training regimen (18.6 ± 2.2, ×10−5 · min−1 · pmol/l−1, P &amp;lt; 0.05). CONCLUSIONS—Mild exercise training at LT improves SG in healthy men with no change in the body composition. Improving not only SI but also SG through mild exercise training is thus considered to be an effective method for preventing glucose intolerance.
Clinical Correlates of Memory in Schizophrenia: Differential Links Between Depression, Positive and Negative Symptoms, and Two Types of Memory Impairment
Authors: G Brébion, M J Smith, X Amador, D Malaspina, J M Gorman
Journal: American Journal of Psychiatry (1997)

This study investigated clinical correlates of memory impairment in schizophrenic patients. In particular, the authors hypothesized that depressive symptoms would be linked to memory efficiency, as found in other clinical populations. In addition, they tested Frith's pathophysiological model predicting links between negative symptoms and failure to respond, as well as between positive symptoms and production of erroneous responses.Thirty-one patients were given several memory tasks: long-term free recall of nonorganizable and organizable lists in immediate and delayed conditions, recognition in immediate and delayed conditions, implicit memory (stem completion task), and short-term memory (digit span). Superficial encoding of information was also assessed by the ability to recall the items sequentially; deep encoding was assessed by the ability to organize the items according to their semantic properties. Two types of memory measures were individualized: measures reflecting memory efficiency and measures reflecting production of erroneous memory responses (intrusions, perseverations, false alarms).Consistent correlations appeared between severity of depressive symptoms and measures reflecting deep but not superficial encoding; none, however, was correlated with negative symptoms. Two of the three types of erroneous memory responses were positively linked to positive symptoms.Efficiency of memory processes relying on deep encoding seemed linked to depressive symptoms. In addition, the two distinct types of impairment predicted by Frith's model were found. The expected link of one with positive symptoms was verified, but the link of the other with negative symptoms was not.
Health-Related Quality-of-Life Parameters as Independent Prognostic Factors in Advanced or Metastatic Bladder Cancer
Authors: D.F. Roychowdhury, A. Hayden, A.M. Liepa
Journal: Journal of Clinical Oncology (2003)

This retrospective analysis examined prognostic significance of health-related quality-of-life (HRQoL) parameters combined with baseline clinical factors on outcomes (overall survival, time to progressive disease, and time to treatment failure) in bladder cancer.Outcome and HRQoL (European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30) data were collected prospectively in a phase III study assessing gemcitabine and cisplatin versus methotrexate, vinblastine, doxorubicin, and cisplatin in locally advanced or metastatic bladder cancer. Prespecified baseline clinical factors (performance status, tumor-node-metastasis staging, visceral metastases [VM], alkaline phosphatase [AP] level, number of metastatic sites, prior radiotherapy, disease measurability, sex, time from diagnosis, and sites of disease) and selected HRQoL parameters (global QoL; all functional scales; symptoms: pain, fatigue, insomnia, dyspnea, anorexia) were evaluated using Cox's proportional hazards model. Factors with individual prognostic value (P <.05) on outcomes in univariate models were assessed for joint prognostic value in a multivariate model. A final model was developed using a backward selection strategy.Patients with baseline HRQoL were included (364 of 405, 90%). The final model predicted longer survival with low/normal AP levels, no VM, high physical functioning, low role functioning, and no anorexia. Positive prognostic factors for time to progressive disease were good performance status, low/normal AP levels, no VM, and minimal fatigue; for time to treatment failure, they were low/normal AP levels, minimal fatigue, and no anorexia. Global QoL was a significant predictor of outcome in univariate analyses but was not retained in the multivariate model.HRQoL parameters are independent prognostic factors for outcome in advanced bladder cancer; their prognostic importance needs further evaluation.
Survival strategies for choosing the right postdoc position
Authors: Duncan T Odom
Journal: Genome biology (2014)

You are completing your PhD (at last!), and might be asking yourself, 'What do I have to accomplish as a postdoc if I want to get a faculty job at one of the top 25% of research universities?' This article is a follow up to last year's essay on picking a graduate studentship, and here I lay out the advice I give to young scientists who have determined that they want to make the next step towards a research faculty post.
Ocular Syndrome in Onchocerciasis
Authors: J. G. Scott
Journal: BMJ (1944)

talent in that field.Not one of the 500 patients consulted me on account of an overt psychiatric condition.... " Among the 500 patients there were 116 (23%) without any discoverable organic cause for the symptoms of which they complained.In addition, there were 56 ~(11 %) presenting minor organic lesions but with symptoms which could not possibly be explained by the lesions alone.In a word, one-third of the patients suffered solely or predominantly from functional disorders."
Gene-based outcome prediction in multiple cohorts of pediatric T-cell acute lymphoblastic leukemia: a Children's Oncology Group study
Authors: Amanda L Cleaver, Alex H Beesley, Martin J Firth, Nina C Sturges, Rebecca A O'Leary, Stephen P Hunger, David L Baker, Ursula R Kees
Journal: Molecular Cancer (2010)

Abstract Background Continuous complete clinical remission in T-cell acute lymphoblastic leukemia (T-ALL) is now approaching 80% due to the implementation of aggressive chemotherapy protocols but patients that relapse continue to have a poor prognosis. Such patients could benefit from augmented therapy if their clinical outcome could be more accurately predicted at the time of diagnosis. Gene expression profiling offers the potential to identify additional prognostic markers but has had limited success in generating robust signatures that predict outcome across multiple patient cohorts. This study aimed to identify robust gene classifiers that could be used for the accurate prediction of relapse in independent cohorts and across different experimental platforms. Results Using HG-U133Plus2 microarrays we modeled a five-gene classifier (5-GC) that accurately predicted clinical outcome in a cohort of 50 T-ALL patients. The 5-GC was further tested against three independent cohorts of T-ALL patients, using either qRT-PCR or microarray gene expression, and could predict patients with significantly adverse clinical outcome in each. The 5-GC featured the interleukin-7 receptor ( IL-7R ), low-expression of which was independently predictive of relapse in T-ALL patients. In T-ALL cell lines, low IL-7R expression was correlated with diminished growth response to IL-7 and enhanced glucocorticoid resistance. Analysis of biological pathways identified the NF-κB and Wnt pathways, and the cell adhesion receptor family (particularly integrins) as being predictive of relapse. Outcome modeling using genes from these pathways identified patients with significantly worse relapse-free survival in each T-ALL cohort. Conclusions We have used two different approaches to identify, for the first time, robust gene signatures that can successfully discriminate relapse and CCR patients at the time of diagnosis across multiple patient cohorts and platforms. Such genes and pathways represent markers for improved patient risk stratification and potential targets for novel T-ALL therapies.
Molecular Mechanisms in Genetically Defined Autoinflammatory Diseases: Disorders of Amplified Danger Signaling
Authors: Adriana Almeida de Jesus, Scott W. Canna, Yin Liu, Raphaela Goldbach-Mansky
Journal: Annual Review of Immunology (2015)

Patients with autoinflammatory diseases present with noninfectious fever flares and systemic and/or disease-specific organ inflammation. Their excessive proinflammatory cytokine and chemokine responses can be life threatening and lead to organ damage over time. Studying such patients has revealed genetic defects that have helped unravel key innate immune pathways, including excessive IL-1 signaling, constitutive NF-κB activation, and, more recently, chronic type I IFN signaling. Discoveries of monogenic defects that lead to activation of proinflammatory cytokines have inspired the use of anticytokine-directed treatment approaches that have been life changing for many patients and have led to the approval of IL-1-blocking agents for a number of autoinflammatory conditions. In this review, we describe the genetically characterized autoinflammatory diseases, we summarize our understanding of the molecular pathways that drive clinical phenotypes and that continue to inspire the search for novel treatment targets, and we provide a conceptual framework for classification.
Akt1 Ablation Inhibits, whereas Akt2 Ablation Accelerates, the Development of Mammary Adenocarcinomas in Mouse Mammary Tumor Virus (MMTV)-ErbB2/Neu and MMTV-Polyoma Middle T Transgenic Mice
Authors: Ioanna G. Maroulakou, William Oemler, Stephen P. Naber, Philip N. Tsichlis
Journal: Cancer Research (2007)

Ample evidence to date links the phosphatidylinositol 3-kinase-regulated protein kinase Akt with the induction and progression of human cancer, including breast cancer. However, there are three Akt isoforms with limited information about their specificity during oncogenesis. This study addresses the role of the three isoforms in polyoma middle T (PyMT) and ErbB2/Neu-driven mammary adenocarcinomas in mice. The effects of ablation of Akt1, Akt2, and Akt3 on the induction and the biology of these tumors were dramatically different, with ablation of Akt1 inhibiting, ablation of Akt2 accelerating, and ablation of Akt3 having a small, not statistically significant, inhibitory effect on tumor induction by both transgenes. Whereas PyMT-induced tumors are all invasive, Akt1(-/-)Neu-induced tumors are more invasive than Akt2(-/-)Neu-induced tumors. Invasiveness, however, does not always correlate with metastasis. Ablation of individual Akt isoforms does not affect the development of the mammary gland during puberty or the expression of the transgenes. Akt ablation, therefore, influences tumor induction by modulating transgene-induced oncogenic signaling. Immunostaining for Ki-67 and cyclin D1 and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assays on tissue sections revealed that the delay of tumor induction in Akt1 knockout mice is due to the inhibitory effects of Akt1 ablation on cell proliferation and survival. Given that these animal models exhibit significant similarities to human breast cancer, the results of the present study may have significant translational implications because they may influence how Akt inhibitors will be used in the treatment of human cancer.
Dynamics of Leukemia Stem-like Cell Extinction in Acute Promyelocytic Leukemia
Authors: Benjamin Werner, Robert E. Gallagher, Elisabeth M. Paietta, Mark R. Litzow, Martin S. Tallman, Peter H. Wiernik, James L. Slack, Cheryl L. Willman, Zhuoxin Sun, Arne Traulsen, David Dingli
Journal: Cancer Research (2014)

Many tumors are believed to be maintained by a small number of cancer stem-like cells, where cure is thought to require eradication of this cell population. In this study, we investigated the dynamics of acute promyelocytic leukemia (APL) before and during therapy with regard to disease initiation, progression, and therapeutic response. This investigation used a mathematical model of hematopoiesis and a dataset derived from the North American Intergroup Study INT0129. The known phenotypic constraints of APL could be explained by a combination of differentiation blockade of PML-RARα-positive cells and suppression of normal hematopoiesis. All-trans retinoic acid (ATRA) neutralizes the differentiation block and decreases the proliferation rate of leukemic stem cells in vivo. Prolonged ATRA treatment after chemotherapy can cure patients with APL by eliminating the stem-like cell population over the course of approximately one year. To our knowledge, this study offers the first estimate of the average duration of therapy that is required to eliminate stem-like cancer cells from a human tumor, with the potential for the refinement of treatment strategies to better manage human malignancy.
What Clinicians Should Know About the QT Interval
Authors: Sana M. Al-Khatib, Nancy M. Allen LaPointe, Judith M. Kramer, Robert M. Califf
Journal: JAMA (2003)

ContextOf the several factors implicated in causing QT interval prolongation and torsades de pointes, errors in the use of medications that may prolong this interval deserve special attention.Objective To systematically summarize the available clinical data on the QT interval and to offer improved recommendations for the use of QT-prolonging medications. Data SourcesWe searched MEDLINE from 1966 through 2002 for all Englishlanguage articles related to the QT interval.Additional data sources included bibliographies of articles identified on MEDLINE, a survey of experts, and data presented at a meeting of experts on long QT syndrome. Study SelectionWe selected for review registries and case series examining clinical outcomes of patients with prolonged QT interval and the effect of different methods of measurement of the QT interval on patient outcomes.Ten studies were identified, of which 6 were included in the analysis.Data Extraction Data quality was determined by publication in the peer-reviewed literature.Data Synthesis Optimal measurement of the QT interval is problematic because of lack of standardization and lack of data regarding the best way to adjust for heart rate.Reliable information on the proper use of QT-prolonging medications is scarce.Although a QT interval of at least 500 milliseconds generally has been shown to correlate with a higher risk of torsades de pointes, there is no established threshold below which prolongation of the QT interval is considered free of proarrhythmic risk.The risk of torsades de pointes should be assessed in patients who are about to begin taking a QT-prolonging medication.Although inadequate clinical studies preclude prediction of absolute risk for individual patients, particularly high-risk situations can be defined based on clinical variables.We propose recommendations on proper monitoring of the QT interval in patients receiving QT-prolonging medications. ConclusionAlthough the use of QT-prolonging medications can predispose to torsades de pointes, there is a relative paucity of information that can help clinicians and patients make optimal informed decisions about how best to minimize the risk of this serious complication.
Human papillomavirus-associated plantar epidermoid cyst related to epidermoid metaplasia of the eccrine duct epithelium: a combined histological, immunohistochemical, DNA-DNA in situ hybridization and three-dimensional reconstruction analysis
Authors: K. Egawa, N. Egawa, Y. Honda
Journal: British Journal of Dermatology (2005)

Background We recently proposed that certain palmoplantar epidermoid cysts may be related to eccrine ducts and that human papillomavirus (HPV) 60 may play a role in their pathomechanism. However, the origin of palmoplantar epidermoid cysts is still controversial. Objectives To examine the contribution of eccrine ducts and HPV 60 in the development of epidermoid cysts. Methods Five epidermoid cysts and four ridged warts that had developed on the soles of a patient were studied histologically, immunohistochemically and by DNA–DNA in situ hybridization. Using serial sections obtained from its entire body, a three‐dimensional reconstruction (3DR) analysis was performed on the smallest cyst to analyse the relationship between the epidermoid cyst, eccrine duct and the overlying epidermis. Results Histological and DNA–DNA in situ hybridization analyses demonstrated both homogeneous intracytoplasmic inclusion bodies pathognomonic for HPV 60 infection and HPV 60 DNA sequences not only in all of the epidermoid cysts and ridged warts but also in the acrosyringeal portion of an eccrine duct, with the dermal portion of which the smallest cyst had been revealed to connect by 3DR analysis. However, immunohistochemical analyses using antibodies against human carcinoembryonic antigen (CEA), involucrin and several cytokeratins (CKs) revealed that the immunoreactivity of the cyst was not identical to that of the eccrine dermal duct but was identical to that of suprabasal layers of the epidermis. Conclusions It was clearly demonstrated that an HPV 60‐associated epidermoid cyst with immunoreactivities for CEA, involucrin and CKs which were identical to those of the epidermis connected with the eccrine dermal duct, supporting the idea that certain palmoplantar epidermoid cysts may develop following the epidermoid metaplasia of eccrine ducts with HPV 60 infection.