tbuckley/cabot-search huggingface dataset:
Cancer Hallmark–Based Gene Sets and Personalized Medicine for Patients With Stage II Colon Cancer
Authors: Greg Yothers, Nan Song, Thomas J. George
Journal: JAMA Oncology (2015)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Oncology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Oncology journal
Shotgun Mitogenomics Provides a Reference Phylogenetic Framework and Timescale for Living Xenarthrans
Authors: Gillian C. Gibb, Fabien L. Condamine, Melanie Kuch, Jacob Enk, Nadia Moraes-Barros, Mariella Superina, Hendrik N. Poinar, Frédéric Delsuc
Journal: Molecular Biology and Evolution (2015)

Xenarthra (armadillos, sloths, and anteaters) constitutes one of the four major clades of placental mammals. Despite their phylogenetic distinctiveness in mammals, a reference phylogeny is still lacking for the 31 described species. Here we used Illumina shotgun sequencing to assemble 33 new complete mitochondrial genomes, establishing Xenarthra as the first major placental clade to be fully sequenced at the species level for mitogenomes. The resulting data set allowed the reconstruction of a robust phylogenetic framework and timescale that are consistent with previous studies conducted at the genus level using nuclear genes. Incorporating the full species diversity of extant xenarthrans points to a number of inconsistencies in xenarthran systematics and species definition. We propose to split armadillos into two distinct families Dasypodidae (dasypodines) and Chlamyphoridae (euphractines, chlamyphorines, and tolypeutines) to better reflect their ancient divergence, estimated around 42 Ma. Species delimitation within long-nosed armadillos (genus Dasypus) appeared more complex than anticipated, with the discovery of a divergent lineage in French Guiana. Diversification analyses showed Xenarthra to be an ancient clade with a constant diversification rate through time with a species turnover driven by high but constant extinction. We also detected a significant negative correlation between speciation rate and past temperature fluctuations with an increase in speciation rate corresponding to the general cooling observed during the last 15 My. Biogeographic reconstructions identified the tropical rainforest biome of Amazonia and the Guiana Shield as the cradle of xenarthran evolutionary history with subsequent dispersions into more open and dry habitats.
Cyclic GMP-Activated Conductance of Retinal Photoreceptor Cells
Authors: K W Yau, D A Baylor
Journal: Annual Review of Neuroscience (1989)

The brain's default mode network consists of discrete, bilateral and symmetrical cortical areas, in the medial and lateral parietal, medial prefrontal, and medial and lateral temporal cortices of the human, nonhuman primate, cat, and rodent brains. Its ...Read More
Zinc finger nuclease-based double-strand breaks attenuate malaria parasites and reveal rare microhomology-mediated end joining
Authors: Mirko Singer, Jennifer Marshall, Kirsten Heiss, Gunnar R. Mair, Dirk Grimm, Ann-Kristin Mueller, Friedrich Frischknecht
Journal: Genome biology (2015)

Genome editing of malaria parasites is key to the generation of live attenuated parasites used in experimental vaccination approaches. DNA repair in Plasmodium generally occurs only through homologous recombination. This has been used to generate transgenic parasites that lack one to three genes, leading to developmental arrest in the liver and allowing the host to launch a protective immune response. While effective in principle, this approach is not safe for use in humans as single surviving parasites can still cause disease. Here we use zinc-finger nucleases to generate attenuated parasite lines lacking an entire chromosome arm, by a timed induction of a double-strand break. Rare surviving parasites also allow the investigation of unconventional DNA repair mechanisms in a rodent malaria parasite. A single, zinc-finger nuclease-induced DNA double-strand break results in the generation of attenuated parasite lines that show varying degrees of developmental arrest, protection efficacy in an immunisation regime and safety, depending on the timing of zinc-finger nuclease expression within the life cycle. We also identify DNA repair by microhomology-mediated end joining with as little as four base pairs, resulting in surviving parasites and thus breakthrough infections. Malaria parasites can repair DNA double-strand breaks with surprisingly small mini-homology domains located across the break point. Timely expression of zinc-finger nucleases could be used to generate a new generation of attenuated parasite lines lacking hundreds of genes.
Phase I study of taxol using a 5-day intermittent schedule.
Authors: S S Legha, D M Tenney, I R Krakoff
Journal: Journal of Clinical Oncology (1986)

Taxol is a plant product derived from the western yew, Taxus brevifolia. We have conducted a phase I clinical study of Taxol used intravenously daily for 5 days at 3-week intervals. The starting dose was 5 mg/m2 daily, and the highest dose used was 40 mg/m2 daily for 5 days. The daily dosage of Taxol was mixed in 250 mL of intravenous fluid and infused over a period of 1 hour. A total of 20 patients with metastatic solid tumors refractory to standard therapy received 45 courses of therapy. Taxol was generally well tolerated and caused no significant nausea or vomiting. A mild degree of diarrhea was reported by six patients, and a moderate degree of stomatitis at the higher dose levels developed in four patients. All patients treated in the dosage range of 20 mg/m2 to 40 mg/m2 experienced nearly complete alopecia. Myelosuppression, predominantly in the form of leukopenia, was the dose-limiting toxicity. The nadir of leukopenia was reached between days 8 and 12 followed by complete recovery between days 15 and 21. Leukopenia was first observed following the Taxol dosage level of 20 mg/m2/d, was moderately severe at the dosage level of 30 mg/m2/d, and was severe at the dosage level of 40 mg/m2/d. No objective tumor regression was observed. A starting dosage level of 30 mg/m2/d for 5 days is recommended for phase II trials using this schedule.
Ethical, behavioral, and social aspects of HIV vaccine trials in developing countries
Authors: P. Lurie
Journal: JAMA (1994)

<h3>Issue.</h3> —Several investigators are preparing to conduct efficacy trials of human immunodeficiency virus (HIV) vaccines in the developing world. Failure to adequately address the unique ethical, behavioral, and social issues that surround vaccine testing in that setting will jeopardize the success of these trials and future acquired immunodeficiency syndrome (AIDS) research in the host nation. <h3>Description of the Project.</h3> —Twelve investigators from Africa, Asia, North America, and South America reviewed previous experience with HIV trials in developing countries and explored potential solutions to these issues. <h3>Conclusions.</h3> —Host country scientists, government officials, and media must be actively involved in all aspects of the trials. Minimum prerequisites for conducting the trial include the following: (1) researching vaccines active against developing world HIV isolates; (2) establishing and maintaining an adequate technological infrastructure; (3) assessing the feasibility of recruitment in countries where the existence of HIV may be denied; (4) designing methods to obtain informed consent from each individual subject, rather than exclusively from family members or community elders; (5) creating locally appropriate instruments to measure risk behavior; (6) identifying a behavioral intervention for placebo and treatment groups; (7) making available laboratory methods to distinguish between natural HIV infection and vaccine-induced seropositivity; and (8) guaranteeing that an effective vaccine is available free of charge to the placebo group and at affordable prices to other host country residents. (<i>JAMA</i>. 1994;271:295-301)
Phenotype of Spirometric Impairment in an Aging Population
Authors: Carlos A. Vaz Fragoso, Gail McAvay, Peter H. Van Ness, Richard Casaburi, Robert L. Jensen, Neil MacIntyre, H. Klar Yaggi, Thomas M. Gill, John Concato
Journal: American Journal of Respiratory and Critical Care Medicine (2015)

The Global Lung Initiative (GLI) provides age-appropriate criteria for establishing spirometric impairment, including mild, moderate, and severe chronic obstructive pulmonary disease (COPD) and restrictive pattern, but its association with respiratory-related phenotypes has not been evaluated.To evaluate respiratory-related phenotypes in GLI-defined spirometric impairment.In COPDGene (N = 10,131 patients; age range, 45-81 yr; average smoking history, 44.3 pack-years), we evaluated spirometry, dyspnea (modified Medical Research Council grade, ≥2), poor respiratory health-related quality of life (St. George's Respiratory Questionnaire total score, ≥25), poor exercise performance (6-minute-walk distance, <391 m), bronchodilator reversibility (FEV1 change, >12% and ≥200 ml), and computed tomography-diagnosed emphysema and gas trapping (>5% and >15% of lung, respectively).GLI established normal spirometry in 5,100 patients (50.3%), mild COPD in 669 (6.6%), moderate COPD in 865 (8.5%), severe COPD in 2,522 (24.9%), and restrictive pattern in 975 (9.6%). Relative to normal spirometry, graded associations with respiratory-related phenotypes were found for mild, moderate, and severe COPD, with respective adjusted odds ratios (95% confidence intervals) as follows: dyspnea-1.31 (1.10-1.56), 2.20 (1.81-2.68), and 10.73 (8.04-14.33); poor respiratory health-related quality of life-1.49 (1.28-1.75), 2.69 (2.08-3.47), and 14.61 (10.09-21.17); poor exercise performance-1.11 (0.94-1.31), 1.58 (1.33-1.88), and 4.58 (3.42-6.12); bronchodilator reversibility-2.76 (2.24-3.40), 5.18 (4.29-6.27), and 6.21 (5.06-7.62); emphysema-4.86 (3.16-7.47), 6.41 (4.09-10.05), and 17.79 (10.79-29.32); and gas trapping-3.92 (3.12-4.93), 5.20 (3.82-7.07), and 16.28 (9.71-27.30). Restrictive pattern was also associated with multiple respiratory-related phenotypes at a level similar to moderate COPD, but it was otherwise not associated with emphysema (0.89 [0.60-1.32]) or gas trapping (1.15 [0.92-1.42]).GLI-defined spirometric impairment establishes clinically meaningful respiratory disease, as validated by graded associations with respiratory-related phenotypes.
Bioactive Fibers: Hydrogel Templates for Rapid Manufacturing of Bioactive Fibers and 3D Constructs (Adv. Healthcare Mater. 14/2015)
Authors: Ali Tamayol, Alireza Hassani Najafabadi, Bahar Aliakbarian, Elmira Arab‐Tehrany, Mohsen Akbari, Nasim Annabi, David Juncker, Ali Khademhosseini
Journal: Advanced Healthcare Materials (2015)

Hybrid hydrogel fibers were fabricated using hydrogel templates. On page 2146, D. Juncker, A. Khademhosseini, and co-workers show how these fibers containing different fluorescent microbeads have been assembled using textile processes, such as braiding and weaving, to create complex 3D patterns for bioengineering applications. The fabricated constructs with clinically relevant dimensions are mechanically stable.
Combined <i>MYC</i> Activation and <i>Pten</i> Loss Are Sufficient to Create Genomic Instability and Lethal Metastatic Prostate Cancer
Authors: Gretchen K. Hubbard, Laura N. Mutton, May Khalili, Ryan P. McMullin, Jessica L. Hicks, Daniella Bianchi-Frias, Lucas A. Horn, Ibrahim Kulac, Michael S. Moubarek, Peter S. Nelson, Srinivasan Yegnasubramanian, Angelo M. De Marzo, Charles J. Bieberich
Journal: Cancer Research (2015)

Genetic instability, a hallmark feature of human cancers including prostatic adenocarcinomas, is considered a driver of metastasis. Somatic copy number alterations (CNA) are found in most aggressive primary human prostate cancers, and the overall number of such changes is increased in metastases. Chromosome 10q23 deletions, encompassing PTEN, and amplification of 8q24, harboring MYC, are frequently observed, and the presence of both together portends a high risk of prostate cancer-specific mortality. In extant genetically engineered mouse prostate cancer models (GEMM), isolated MYC overexpression or targeted Pten loss can each produce early prostate adenocarcinomas, but are not sufficient to induce genetic instability or metastases with high penetrance. Although a previous study showed that combining Pten loss with focal MYC overexpression in a small fraction of prostatic epithelial cells exhibits cooperativity in GEMMs, additional targeted Tp53 disruption was required for formation of metastases. We hypothesized that driving combined MYC overexpression and Pten loss using recently characterized Hoxb13 transcriptional control elements that are active in prostate luminal epithelial cells would induce the development of genomic instability and aggressive disease with metastatic potential. Neoplastic lesions that developed with either MYC activation alone (Hoxb13-MYC) or Pten loss alone (Hoxb13-Cre∣Pten(Fl/Fl)) failed to progress beyond prostatic intraepithelial neoplasia and did not harbor genomic CNAs. By contrast, mice with both alterations (Hoxb13-MYC∣Hoxb13-Cre∣Pten(Fl/Fl), hereafter, BMPC mice) developed lethal adenocarcinoma with distant metastases and widespread genome CNAs that were independent of forced disruption of Tp53 and telomere shortening. BMPC cancers lacked neuroendocrine or sarcomatoid differentiation, features uncommon in human disease but common in other models of prostate cancer that metastasize. These data show that combined MYC activation and Pten loss driven by the Hoxb13 regulatory locus synergize to induce genomic instability and aggressive prostate cancer that phenocopies the human disease at the histologic and genomic levels.
Neutrophil Specific Granule Deficiency
Authors: J I Gallin
Journal: Annual Review of Medicine (1985)

Neutrophil specific granules are thought to be important in the evolution of the inflammatory response. Specific granules are preferentially released with minor membrane perturbation in vitro or in vivo, and secreted products probably have important effects on humoral and cellular components of inflammation. In vitro studies reveal that some secreted specific granule products activate the complement cascade to generate the chemoattractant C5a and the opsonin C3b, while other secreted products are selectively chemotactic for monocytes. Translocation of receptors for chemoattractants (fmet-leu-phe) and opsonins (C3bi) from specific granules or closely related organelles to the plasma membrane may play an important role in chemotaxis, adherence, and phagocytosis. Similar translocation of constituents of the electron transport chain involved in the respiratory burst (i.e. cytochrome b) probably plays a role in neutrophil oxidative metabolism and hydrogen peroxide generation. In vivo and in vitro studies of neutrophils from patients with congenital specific granule deficiency, acquired specific granule deficiency (thermal injury and neonates), or normal neutrophils experimentally depleted of nuclei and organelles support these conclusions. Thus, release of specific granule constituents appears to be important for amplification of the initial and subsequent phases of the inflammatory response.
Gene rearrangements as markers of clonal variation and minimal residual disease in acute lymphoblastic leukemia.
Authors: J J Wright, D G Poplack, A Bakhshi, G Reaman, D Cole, J P Jensen, S J Korsmeyer
Journal: Journal of Clinical Oncology (1987)

Immunoglobulin (Ig) heavy (H) and light (L) chain gene rearrangements were used as molecular markers of clonal evolution and minimal residual disease in B cell precursor acute lymphoblastic leukemia (ALL). All leukemic episodes within individual patients shared at least one identical Ig rearrangement and thus arose from a common clonal progenitor cell. Nine of 11 patients displayed completely identical patterns between leukemic episodes, while two of 11 patients demonstrated genetic progression between diagnosis and relapse as evidenced by additional rearrangements. These genetic changes marked the emergence of leukemic subclones. Ig gene rearrangements were also used as sensitive markers to identify clonal cell populations in ALL patients following induction or reinduction therapy and to search for residual bone marrow disease in patients in clinical remission or with isolated extramedullary relapse. DNA rearrangements provide tumor-specific markers to follow the genetic variation of ALL and may facilitate the early detection of recurrent disease.
Induction of targeted, heritable mutations in barley and Brassica oleracea using RNA-guided Cas9 nuclease
Authors: Tom Lawrenson, Oluwaseyi Shorinola, Nicola Stacey, Chengdao Li, Lars Østergaard, Nicola Patron, Cristobal Uauy, Wendy Harwood
Journal: Genome biology (2015)

The RNA-guided Cas9 system represents a flexible approach for genome editing in plants. This method can create specific mutations that knock-out or alter target gene function. It provides a valuable tool for plant research and offers opportunities for crop improvement. We investigate the use and target specificity requirements of RNA-guided Cas9 genome editing in barley (Hordeum vulgare) and Brassica oleracea by targeting multicopy genes. In barley, we target two copies of HvPM19 and observe Cas9-induced mutations in the first generation of 23 % and 10 % of the lines, respectively. In B. oleracea, targeting of BolC.GA4.a leads to Cas9-induced mutations in 10 % of first generation plants screened. In addition, a phenotypic screen identifies T0 plants with the expected dwarf phenotype associated with knock-out of the target gene. In both barley and B. oleracea stable Cas9-induced mutations are transmitted to T2 plants independently of the T-DNA construct. We observe off-target activity in both species, despite the presence of at least one mismatch between the single guide RNA and the non-target gene sequences. In barley, a transgene-free plant has concurrent mutations in the target and non-target copies of HvPM19. We demonstrate the use of RNA-guided Cas9 to generate mutations in target genes of both barley and B. oleracea and show stable transmission of these mutations thus establishing the potential for rapid characterisation of gene function in these species. In addition, the off-target effects reported offer both potential difficulties and specific opportunities to target members of multigene families in crops.
‘Moneyball’ and time to be honest about preseason screening: it is a sham making no inroads on the 1 billion dollar injury costs in baseball
Authors: Rod Whiteley
Journal: British Journal of Sports Medicine (2015)

Injuries cost Major League Baseball teams over 1 billion dollars in 2014; that is enough to buy all but 4 of the 30 Major League Baseball teams outright.1 Improving performance and saving money by preventing injury in the players is a high priority, and one justification for preseason physical screening.

On the surface, this seems sensible, but so did the player scouting practices of the last century, which the statisticians subsequently thoroughly debunked. In the Moneyball age,2 baseball players are bought and sold on fractional differences in performance statistics—there is little room for unfounded hunches. How does screening stand up in the Moneyball age? I argue that screening as we now do it is the same as player evaluation was years ago—it sounds like a good idea, but we are kidding ourselves if we think it is preventing injury.

Typical preseason physical screening involves some physical (eg, flexibility, strength, control) and some orthopaedic tests that are purported to detect undiagnosed …
Home visiting by general practitioners in England and Wales
Authors: T. Marshall
Journal: BMJ (1996)

Home visiting by general practitioners in England and WalesHome visits are a feature of primary care in many western European countries EDITOR,-Paul Aylin and colleagues' paper on home visiting in general practice perpetuates one of the many myths concerning the NHS.1 It is not true that home visiting "is one of the factors that distinguish primary care in Britain from pri- mary care in many other Western countries."Home visits are a feature ofprimary care in many Western countries, and also in the former social- ist countries of central and eastern Europe.In 1994 they accounted for about 3% of face to face consultations in general practice in Denmark, under 1% in Finland, 19% in France, 9% in Germany, 5% in Greece, 3% in Israel, 11% in Italy, 9% in the Netherlands, 2% in Portugal, 3% in Spain, 2% in Sweden, and 7% in the United Kingdom.2This makes the United Kingdom about average for western Europe.Among central and eastern European countries, home
Calcium Action in Synaptic Transmitter Release
Authors: G J Augustine, M P Charlton, S J Smith
Journal: Annual Review of Neuroscience (1987)

In this review we are concerned with the mechanisms by which the electrical potential across the membrane of presynaptic nerve terminals regulates the release of neurotransmitter substances into the synaptic cleft .  ions play a central role in this process: Release occurs when a voltage-depen­ dent  channel in the presynaptic membrane opens, thus permitting an influx of  ions and diffusion of  in cytoplasm, followed by binding of  at some cytoplasmic site that triggers the exocytotic release of quanta of neurotransmitter. These concepts, introduced mainly by the work of Katz and associates (Katz 1 969), comprise the Ca  of trans­ mitter release, a hypothesis now widely accepted. Although the general role of  as a presynaptic messenger is well supported, many important specifics of its action remain to be resolved. We review progress with these details in three parts, corresponding to