tbuckley/cabot-search huggingface dataset:
Screening Mammography for Women 40 to 49 Years of Age: A Clinical Practice Guideline from the American College of Physicians
Authors: Amir Qaseem, Vincenza Snow, Katherine Sherif, Mark Aronson, Kevin B. Weiss, Douglas K. Owens
Journal: Annals of Internal Medicine (2007)

Breast cancer is one of the most common causes of death for women in their 40s in the United States. Individualized risk assessment plays an important role when making decisions about screening mammography, especially for women 49 years of age or younger. The purpose of this guideline is to present the available evidence for screening mammography in women 40 to 49 years of age and to increase clinicians' understanding of the benefits and risks of screening mammography. *This paper, written by Amir Qaseem, MD, PhD, MHA; Vincenza Snow, MD; Katherine Sherif, MD; Mark Aronson, MD; Kevin B. Weiss, MD, MPH; and Douglas K. Owens, MD, MS, was developed for the Clinical Efficacy Assessment Subcommittee of the American College of Physicians (ACP): Douglas K. Owens, MD, MS (Chair); Mark Aronson, MD; Patricia Barry, MD, MPH; Donald E. Casey Jr., MD, MPH, MBA; J. Thomas Cross Jr., MD, MPH; Nick Fitterman, MD; E. Rodney Hornbake, MD; Katherine D. Sherif, MD; and Kevin B. Weiss, MD, MPH (Immediate Past Chair). Approved by the ACP Board of Regents on 15 July 2006.
Gonadal function in male and female patients with classic galactosemia
Authors: M.E. Rubio-Gozalbo, C.S. Gubbels, J.A. Bakker, P.P.C.A. Menheere, W.K.W.H. Wodzig, J.A. Land
Journal: Human Reproduction Update (2009)

Hypergonadotropic hypoestrogenic infertility is the most burdensome complication for females suffering from classic galactosemia. In contrast, male gonadal function seems less affected. The underlying mechanism is not understood and several pathogenic mechanisms have been proposed. Timing of the lesion, prenatal or chronic post-natal, or a combination of both are not yet clear. This review focuses on gonadal function in males and females, ovarian imaging and histology in this disease. It is based on the literature known to the authors and a Pubmed search using the keywords galactosemia, GALT deficiency, (premature) ovarian failure/insufficiency/dysfunction, testicular function, gonadotrophins, FSH, LH (published between January 1971 and April 2009). Male gonads are less affected, boys spontaneously reach puberty, although onset can be delayed. Semen quality has not been extensively studied. Several affected males are known to have fathered a child. Female gonads are invariably affected, although to a varied extent (hypergonadotropic hypoestrogenic ovarian dysfunction). Intriguingly, FSH is often already increased in infancy. Imaging usually shows hypoplastic and streak-like ovaries. Histological findings in some cases reveal the presence of morphologically normal but decreased numbers of primordial follicles, with the absence of intermediate and Graafian follicles. Gonads in males seem less affected than in females who exhibit hypergonadotropic hypoestrogenic subfertility. FSH can be elevated in infancy, and ovarian histology sometimes shows the presence of normal primordial follicles with absence of intermediate and Graafian follicles. These findings are similar to other genetic diseases primarily affecting the ovary.
Value of Meetings Is Far from Abstract
Authors: W. K. Alfred Yung
Journal: Neuro-Oncology (2008)

It’s that time of year again—if you aren’t at a meeting, you are preparing to go to a meeting or submitting an abstract for a meeting or reading about all the meetings you will miss.

Naturally, most of us have to pick and choose where to spend our travel budgets and how best to leverage our time away from our practices and laboratories. Meetings are vital for keeping up-to-date with the rapid advances in the practice of neuro-oncology and the scientific breakthroughs that engender those advances.

On a practical level, nothing can replace the face-to-face contact that comes from attending professional conferences and seminars, and many successful collaborations have originated in the chance (or not so chance) conversations that occurred at a reception or outside the meeting room after a particularly lively Q&A during a scientific session. As editors, we take the opportunity of a good conference to hear what you are working on and seeing in your research, the problems you face as clinicians— in short, the questions you are trying to answer and the questions you need answered to guide your work.

But because you cannot be at every meeting, we feel it is important for Neuro-Oncology to give you the opportunity to at least get a feel for the “meeting space” by showcasing the abstracts of the oral presentations and posters from some key venues. For instance, the International Symposium on Pediatric Neuro-Oncology, now in its thirteenth iteration, has worked with this journal many times in the past to facilitate publication of its meeting abstracts. This year’s offerings begin on page 369 and faithfully reflect the full spectrum of the symposium’s technical and scientific program (a program that is unique in its ability to include first-hand accounts of patients’ and families’ experiences of pediatric CNS cancers).

Later this year, we will publish abstracts from the Eighth Congress of the European Association of Neuro-Oncology (EANO), which is being held in Barcelona. EANO is, of course, one of our sponsoring societies and so has premier access to our pages. Likewise, this fall you will receive an issue that contains all the meeting abstracts for SNO 2008, which is being held in Las Vegas, Nevada, in November. This year’s meeting is anticipated to be bigger and better than ever, with updated presentation categories (to reflect the evolving science) and a new feature: Select Poster Review sessions, which will feature the top-rated posters for attendee review and related discussion by an invited speaker.

We still hope to bump into you at a meeting, but if you cannot make it, we hope that giving you access to the abstracts will still help you gain some of the advantages of attending by keeping you up-to-date on the cutting-edge work that hasn’t quite reached the manuscript stage and that otherwise might not make it into our pages at all.
Phase I/II Study of Preoperative Oxaliplatin, Fluorouracil, and External-Beam Radiation Therapy in Patients With Locally Advanced Rectal Cancer: Cancer and Leukemia Group B 89901
Authors: David P. Ryan, Donna Niedzwiecki, Donna Hollis, Brent E. Mediema, Scott Wadler, Joel E. Tepper, Richard M. Goldberg, Robert J. Mayer
Journal: Journal of Clinical Oncology (2006)

The addition of oxaliplatin to fluorouracil in patients with advanced colorectal cancer improves survival. This phase I/II study evaluated the addition of weekly oxaliplatin to preoperative continuous infusion fluorouracil (FU) and external-beam radiation therapy (RT) in patients with locally advanced rectal adenocarcinoma.Patients with clinical T3/T4 rectal adenocarcinoma and no evidence of metastases were treated with weekly oxaliplatin, continuous infusion FU 200 mg/m2 intravenously, and RT. A total of 6 weekly doses of oxaliplatin were planned. RT dose was 1.8 Gy/fraction to a total dose of 50.4 Gy. In the phase I portion, oxaliplatin was escalated from 30 to 60 mg/m2.Forty-four patients were entered onto the study, 18 on the phase I portion and 26 on the phase II portion. The maximum-tolerated dose (MTD) for oxaliplatin was determined to be 60 mg/m2. At the MTD, 12 patients experienced grade 3 or 4 diarrhea, two patients experienced grade 3 neutropenia, and one patient experienced grade 3 thrombocytopenia. Fifty-six percent of patients entered at the MTD completed all 6 weeks of oxaliplatin. Eight (25%) of 32 patients enrolled at the phase II dose experienced a pathologic complete response.In this multicenter study, the addition of oxaliplatin to intravenous continuous infusion FU and RT for patients with locally advanced rectal cancer was associated with a high pathologic complete response rate but more toxicity than when FU is used alone. A regimen of weekly oxaliplatin, continuous infusion FU, and radiation therapy is now being evaluated by the National Surgical Adjuvant Breast and Bowel Project.
Transient regulatory T cell ablation deters oncogene-driven breast cancer and enhances radiotherapy
Authors: Paula D. Bos, George Plitas, Dipayan Rudra, Sue Y. Lee, Alexander Y. Rudensky
Journal: The Journal of Experimental Medicine (2013)

Rational combinatorial therapeutic strategies have proven beneficial for the management of cancer. Recent success of checkpoint blockade in highly immunogenic tumors has renewed interest in immunotherapy. Regulatory T (T reg) cells densely populate solid tumors, which may promote progression through suppressing anti-tumor immune responses. We investigated the role of T reg cells in murine mammary carcinogenesis using an orthotopic, polyoma middle-T antigen-driven model in Foxp3DTR knockin mice. T reg cell ablation resulted in significant determent of primary and metastatic tumor progression. Importantly, short-term ablation of T reg cells in advanced spontaneous tumors led to extensive apoptotic tumor cell death. This anti-tumor activity was dependent on IFN-γ and CD4+ T cells but not on NK or CD8+ T cells. Combination of T reg cell ablation with CTLA-4 or PD-1/PD-L1 blockade did not affect tumor growth or improve the therapeutic effect attained by T reg cell ablation alone. However, T reg cell targeting jointly with tumor irradiation significantly reduced tumor burden and improved overall survival. Together, our results demonstrate a major tumor-promoting role of T reg cells in an autochthonous model of tumorigenesis, and they reveal the potential therapeutic value of combining transient T reg cell ablation with radiotherapy for the management of poorly immunogenic, aggressive malignancies.
A methylated oligonucleotide inhibits IGF2 expression and enhances survival in a model of hepatocellular carcinoma
Authors: Xiaoming Yao, Ji-Fan Hu, Mark Daniels, Hadas Shiran, Xiangjun Zhou, Huifan Yan, Hongqi Lu, Zhilan Zeng, Qingxue Wang, Tao Li, Andrew R. Hoffman
Journal: Journal of Clinical Investigation (2003)

IGF-II is a mitogenic peptide that has been implicated in hepatocellular oncogenesis. Since the silencing of gene expression is frequently associated with cytosine methylation at cytosine-guanine (CpG) dinucleotides, we designed a methylated oligonucleotide (MON1) complementary to a region encompassing IGF2 promoter P4 in an attempt to induce DNA methylation at that locus and diminish IGF2 mRNA levels. MON1 specifically inhibited IGF2 mRNA accumulation in vitro, whereas an oligonucleotide (ON1) with the same sequence but with nonmethylated cytosines had no effect on IGF2 mRNA abundance. MON1 treatment led to the specific induction of de novo DNA methylation in the region of IGF2 promoter hP4. Cells from a human hepatocellular carcinoma (HCC) cell line, Hep 3B, were implanted into the livers of nude mice, resulting in the growth of large tumors. Animals treated with MON1 had markedly prolonged survival as compared with those animals treated with saline or a truncated methylated oligonucleotide that did not alter IGF2 mRNA levels in vitro. This study demonstrates that a methylated sense oligonucleotide can be used to induce epigenetic changes in the IGF2 gene and that inhibition of IGF2 mRNA accumulation may lead to enhanced survival in a model of HCC.
Synovial tissue inflammation in early and late osteoarthritis
Authors: M J Benito
Journal: Annals of the Rheumatic Diseases (2005)

<b>Objective:</b> To compare selected immunohistological features of inflammation in synovial tissue from patients with early and late osteoarthritis (OA). <b>Methods:</b> Synovial tissue samples were obtained from 10 patients with knee pain, normal radiographs, and arthroscopic manifestations of OA (early OA), and from 15 patients with OA undergoing knee joint arthroplasty (late OA). Conventional immunohistochemical techniques were used to measure microscopic manifestations of inflammation. The inflammatory cell infiltrate, blood vessel formation, and angiogenic factors, NF-κB activation, expression of tumour necrosis factor α (TNFα) and interleukin 1β (IL1β), and the presence of cyclo-oxygenase (COX)-1 and COX-2 were quantified. Fibroblast-like synoviocytes (FLS) were isolated from early and late OA tissue samples to compare in vitro production of prostaglandin E<sub>2</sub> (PGE<sub>2</sub>) <b>Results:</b> Synovial tissue from patients with early OA demonstrated significantly greater CD4+ (p = 0.017) and CD68+ (p&lt;0.001) cell infiltration, blood vessel formation (p = 0.01), vascular endothelial growth factor (p = 0.001), and intercellular adhesion molecule-1 expression (p&lt;0.001). Numbers of cells producing TNFα and IL1β were also significantly greater in early OA (p&lt;0.001). Manifestations of inflammation in early OA were associated with increased expression of the NF-κB1 (p&lt;0.001) and RelA (p = 0.015) subunits, and with increased COX-2 expression (p = 0.04). Cytokine-induced PGE<sub>2</sub> production by cultured FLS was similar in both groups. <b>Conclusion:</b> Increased mononuclear cell infiltration and overexpression of mediators of inflammation were seen in early OA, compared with late OA. Isolated FLS were functionally similar in both groups, consistent with microenvironmental differences in the synovial tissue during different phases of OA. These observations may have important therapeutic implications for some patients during the early evolution of OA.
Farmer's lung: A clinical, radiographic, functional, and serological correlation of acute and chronic stages
Authors: E. J. Hapke, R. M. E. Seal, G. O. Thomas, M. Hayes, J. C. Meek
Journal: Thorax (1968)

In assessing patients suffering from farmer9s lung, the acute stage must be distinguished from the chronic stage of the disease. The conspicuous radiographic signs in the acute farmer9s lung episode and the often dramatic clearing make an important contribution to the diagnosis. The radiographic changes in chronic farmer9s lung are not specific and cover a wide range of appearances. Even minor nodular changes are significant. Farmer9s lung, acute and chronic, is not a disease predominantly characterized by a defect in gas exchange. During the acute illness the reduction in diffusing capacity is often accompanied by a decrease in lung volumes; the pulmonary function profile of the chronic stage is variable. In only a relatively small proportion of chronic farmer9s lung patients does a defect in gas exchange predominate, and in some it may be manifest only during exercise. Airway obstruction is a feature of chronic farmer9s lung. In chronic farmer9s lung patients discrepancies between the severity of complaints and results of pulmonary function tests are not infrequent. In some patients with considerable disability conventional pulmonary function studies may demonstrate little or no impairment of the functions measured. In patients suffering from an acute farmer9s lung episode, serological tests should be positive, possibly in high titre. In the chronic stage of the disease the chance of finding positive serology in a patient diminishes with the length of time elapsed since the last acute episode. The period of serological transition appears to be the third year.
AN IMMUNOCHEMICAL STUDY OF THE ALBUMINS OF SERUM, URINE, ASCITIC FLUID AND EDEMA FLUID IN THE NEPHROTIC SYNDROME 12
Authors: David Gitlin, Charles A. Janeway
Journal: Journal of Clinical Investigation (1952)

With the introduction of the Tiselius apparatus, the Howe method for the separation of albumin and globulins in serum and urine was shown to be in serious error, particularly where the proportion of albumin was low (12). Longsworth and MacInnes (13) and Luetscher (12) showed that the albumin content was very low in nephrotic serum and that the pattern of the urinary proteins in the nephrotic syndrome resembled that of  serum. These findings would serve to explain many of the abnormalities of the albumins obtained by salt fractionation of nephrotic serum. However, Luetscher did observe that in nephrotic serum and urine the ratio of the two components of albumin separated by electrophoresis at pH 4.0 was reversed from the normal and he postulated an abnormality in the metabolism of albumin in this syndrome.
Evolution of a Perfect Simple Sequence Repeat Locus in the Context of Its Flanking Sequence
Authors: Scott M. Blankenship, Bernie May, Dennis Hedgecock
Journal: Molecular Biology and Evolution (2002)

Microsatellites, which have rapidly become the preferred markers in population genetics, reliably assign individual chinook salmon to the winter, fall, late-fall, or spring chinook runs in the Sacramento River in California's Central Valley (Banks et al. 2000 . Can. J. Fish. Aquat. Sci. 57:915–927). A substantial proportion of this discriminatory power comes from Ots-2, a simple CA repeat, which is expected to evolve rapidly under the stepwise mutation model. We have sequenced a 300-bp region around this locus and typed 668 microsatellite-flanking sequence haplotypes to explore further the basis of this microsatellite divergence. Three sites of nucleotide polymorphism in the Ots-2 flanking sequence define five haplotypes that are shared by the Californian and Canadian populations. The Ots-2 microsatellite alleles are nonrandomly distributed among these five haplotypes in a pattern of gametic disequilibrium that is also shared among populations. Divergence between the winter run and other Central Valley stocks appears to be caused by a combination of surprisingly static evolution at Ots-2 within a context of more rapidly changing haplotype frequencies.
Terguride ameliorates monocrotaline-induced pulmonary hypertension in rats
Authors: R. Dumitrascu, C. Kulcke, M. Königshoff, F. Kouri, X. Yang, N. Morrell, H.A. Ghofrani, N. Weissmann, R. Reiter, W. Seeger, F. Grimminger, O. Eickelberg, R.T. Schermuly, S.S. Pullamsetti
Journal: European Respiratory Journal (2010)

Pulmonary arterial hypertension (PAH) is a life-threatening disease characterised by vasoconstriction and remodelling of the pulmonary vasculature. The serotonin (5-hydroxytryptamine (5-HT)) pathway has been shown to play a major role in the pathogenesis of PAH, but pharmacological modulation of this pathway for treatment of PAH is, to date, at a pre-clinical level. Terguride is a 5-HT receptor (5-HTR) antagonist that is well tolerated and clinically approved for ovulation disorders. Immunohistochemistry against 5-HTR 2A/B on human lungs revealed their localisation to the vascular smooth muscle layer and quantitative RT-PCR showed 5-HTR 2B upregulation in pulmonary artery smooth muscle cells (PASMC) isolated from PAH patients. Proliferation and migration of cultured primary human PASMC were dose-dependently blocked by terguride. Therapeutic 5-HT signalling inhibition was 1) demonstrated in isolated, ventilated and perfused rat lungs and 2) by chronic terguride treatment of rats with monocrotaline (MCT)-induced pulmonary hypertension in a preventive or curative approach. Terguride inhibited proliferation of PASMCs and abolished 5-HT-induced pulmonary vasoconstriction. Chronic terguride treatment prevented dose-dependently the development and progression of MCT-induced PAH in rats. Thus, terguride represents a valuable novel therapeutic approach in PAH.
Estimate of Lung Cancer Mortality From Low-Dose Spiral Computed Tomography Screening Trials: Implications for Current Mass Screening Recommendations
Authors: Edward F. Patz, Stephen J. Swensen, James E. Herndon
Journal: Journal of Clinical Oncology (2004)

Low-dose computed tomography (CT) has been suggested for lung cancer screening. Several observational trials have published their preliminary results, and some investigators suggest that this technique will save lives. There are no mortality statistics, however, and the current study used published data from these trials to estimate the disease-specific mortality in this high-risk population.Two nonrandomized CT screening trials were selected from the literature for analysis. The number of trial participants, the number of lung cancers diagnosed per year, and stage distribution of the cancers was recorded. Previously published 5-year survival data were used to calculate the number of predicted lung cancer deaths and estimate the overall lung cancer mortality per 1,000 person-years among participants screened. These statistics were then compared to the previous Mayo Lung Project, which used chest radiographs and sputum cytology for screening high-risk individuals.This study estimates the lung cancer mortality is 4.1 deaths per 1,000 person-years in the Mayo Clinic CT screening trial, and is 5.5 deaths per 1,000 person-years in the Early Lung Cancer Action Program trial. These data are similar to the lung cancer mortality of 4.4 deaths per 1,000 person-years in the interventional arm, and 3.9 deaths per 1,000 person-years in the usual-care arm of the previous Mayo Lung Project.These data suggest that CT screening could produce similar outcomes to prior chest radiographic trials in this high-risk group. Results from randomized trials are required, however, before the true utility of mass screening with CT for lung cancer can be determined.
Evolution of the Telencephalon in Nonmammals
Authors: R G Northcutt
Journal: Annual Review of Neuroscience (1981)

Comparative studies of the vertebrate telencephalon began in the late eighteenth and early nineteenth centuries with descriptions of gross mor­ phology (Cuvier 1 809, Owen 1866); however, not until the late nineteenth and early twentieth centuries was the internal anatomy of the telencephalon described for a wide variety of vertebrates (Johnston 1906, Edinger 1908, Ramon y Cajal 1908, Papez 1929, Ariens Kappers et al 1936). This period of intensive study yielded a number of hypotheses regarding the evolution of the vertebrate telencephalon. These hypotheses were based on the anatomy revealed by existing methods-methods that allow what is now referred to as descriptive anatomy-and this anatomy could not be con­ firmed experimentally because the appropriate experimental techniques did not yet exist. In addition, these hypotheses refl ec ted anatomical assump­ tions grounded in scala naturae, which held that vertebrates form one linear series and reflect increasing complexity. The relatively sophisticated armamentarium of neurobiological tech­ niques available today allows us to establish more accurately the anatomy of the telencephalon; these data, data from the fossil record, and a more sophisticated view of vertebrate phylogeny allow us to propose and test new hypotheses regarding the evolution of the vertebrate telencephalon.