tbuckley/cabot-search huggingface dataset:
TREATMENT OF UTERINE FIBROIDS.
Journal: JAMA (1893)

Hysteromyoma reproductive system of women of childbearing age are the most common benign tumor,mainly composed of smooth muscle fibers,so called uterine smooth muscle,referred to as uterine fibroids.In women of childbearing age in the incidence rate is as high as 20%～40%,particularly in the hair are many 30 to 50-year-old women,the prevalence rate is as high as 70%～ 80%,about 50% of patients will show symptoms.In recent years,drug therapy and surgical treatment of uterine fibroids has been the traditional treatment,but drug therapy can improve symptoms and reduce the fibroid,but no cure for uterine fibroids,So the current treatment for uterine fibroids is still mainly of surgical treatment and gradually to the minimally invasive and the retention of the uterus direction.
TBCRC-010: Phase I/II Study of Dasatinib in Combination with Zoledronic Acid for the Treatment of Breast Cancer Bone Metastasis
Authors: Zahi Mitri, Rita Nanda, Kimberly Blackwell, Colleen M. Costelloe, Ilona Hood, Caimiao Wei, Abenaa M. Brewster, Nuhad K. Ibrahim, Kimberly B. Koenig, Gabriel N. Hortobagyi, Catherine Van Poznak, Mothaffar F. Rimawi, Stacy Moulder-Thompson
Journal: Clinical Cancer Research (2016)

Osteoclast-mediated bone resorption through src kinase releases growth factors, sustaining bone metastases. This trial determined the recommended phase II dose (RP2D) and clinical efficacy of the src kinase inhibitor dasatinib combined with zoledronic acid in bone predominant, HER2-negative breast cancer metastases.A 3+3 lead in phase I design confirmed the RP2D allowing activation of the single-arm, phase II trial. Zoledronic acid was administered intravenously on day 1, and dasatinib was given orally once daily for 28 days each cycle as twice daily administration caused dose-limiting toxicity (DLT). Response was assessed every three cycles. N-telopeptide (NTx) was serially measured.A total of 25 patients were enrolled. No DLTs were noted at the RP2D of dasatinib = 100 mg/d. Common adverse events were grade 1-2: rash (9/25, 36%), fatigue (9/25, 36%), pain (9/25, 36%), nausea (6/25, 20%). The objective response rate in bone was 5/22 (23%), all partial responses (PR). The clinical benefit rate [PRs + stable disease (SD) ≥ 6 months] in bone was 8/22 (36%). Median time to treatment failure was 2.70 months [95% confidence interval (CI), 1.84-5.72] in the general cohort, 3.65 months (95% CI, 1.97-7.33) in patients with hormone receptor (HR)-positive breast cancer and 0.70 months (95% CI, 0.30-NA) in those with HR-negative disease. Factors associated with response in bone included lower tumor grade, HR-positive status, and pretreatment high NTx levels.Combination therapy was well tolerated and produced responses in bone in patients with HR-positive tumors. Clin Cancer Res; 22(23); 5706-12. ©2016 AACR.
&lt;TITLE&gt;Protecting our children&lt;/TITLE&gt;
Authors: B Walker
Journal: JAMA (1998)

American society will face major economic and social difficulties in the years to come if we do not address the serious threat to our prosperity posed by the growing numbers of young people who lack the education to function in a highly technical world. The author identifies some of the circumstances and behaviors that place children at risk of academic failure, including poverty, teenage pregnancy, drug abuse, unstable families, and suicide. Failure of the education, health, and social service systems set up to deal with these risk factors is also identified as part of the problem. The author offers four proposals for restructuring failing systems to provide our youth with the support they need to mature, learn, and develop.
The C1q Binding Test for Soluble Immune Complexes: Clinical Correlations Obtained in Patients With Cancer 2
Authors: R. D. Rossen, M.A. Reisberg, E. M. Hersh, J. U. Gutterman
Journal: JNCI Journal of the National Cancer Institute (1977)

Sera from 134 selected patients with various types of cancer were tested for soluble antigen-antibody complexes by the C1q binding method. Sera from 85 healthy blood bank donors served as normal controls. C1q binding activity (C1q BA) values above the 95th percentile for healthy subjects were found in 83% of sera from patients with neoplastic diseases. The incidence of abnormal C1q BA values among patients with malignant melanoma was 83%, with breast cancer 74%, with colon cancer 75%, with lung cancer 88%, with leukemia and lymphoma 85%, and with miscellaneous tumors 94%. High C1q BA values were found most frequently in sera of patients who had been diagnosed relatively recently (within 5 mo) and who had evident residual disease after surgical treatment. Recurrence or progression of tumor growth occurred significantly more frequently in lung cancer patients with high C1q BA. DNA was not detected in cancer patients' sera and treatment with DNase did not decrease in C1q BA. C1q BA in sera could not be explained by the presence of antiglobulin antibodies. Sucrose density gradient ultracentrifugation studies of the serum C1q BA in 4 cancer patients showed that the major binding activity was found between 19S and 7S.
Advancing Exposure Science through Chemical Data Curation and Integration in the Comparative Toxicogenomics Database
Authors: Cynthia J. Grondin, Allan Peter Davis, Thomas C. Wiegers, Benjamin L. King, Jolene A. Wiegers, David M. Reif, Jane A. Hoppin, Carolyn J. Mattingly
Journal: Environmental Health Perspectives (2016)

Exposure science studies the interactions and outcomes between environmental stressors and human or ecological receptors. To augment its role in understanding human health and the exposome, we aimed to centralize and integrate exposure science data into the broader biological framework of the Comparative Toxicogenomics Database (CTD), a public resource that promotes understanding of environmental chemicals and their effects on human health.We integrated exposure data within the CTD to provide a centralized, freely available resource that facilitates identification of connections between real-world exposures, chemicals, genes/proteins, diseases, biological processes, and molecular pathways.We developed a manual curation paradigm that captures exposure data from the scientific literature using controlled vocabularies and free text within the context of four primary exposure concepts: stressor, receptor, exposure event, and exposure outcome. Using data from the Agricultural Health Study, we have illustrated the benefits of both centralization and integration of exposure information with CTD core data.We have described our curation process, demonstrated how exposure data can be accessed and analyzed in the CTD, and shown how this integration provides a broad biological context for exposure data to promote mechanistic understanding of environmental influences on human health.Curation and integration of exposure data within the CTD provides researchers with new opportunities to correlate exposures with human health outcomes, to identify underlying potential molecular mechanisms, and to improve understanding about the exposome.Grondin CJ, Davis AP, Wiegers TC, King BL, Wiegers JA, Reif DM, Hoppin JA, Mattingly CJ. 2016. Advancing exposure science through chemical data curation and integration in the Comparative Toxicogenomics Database. Environ Health Perspect 124:1592-1599; http://dx.doi.org/10.1289/EHP174.
Coronary Vasomotor Control in Obesity and Morbid Obesity
Authors: Alessandra Quercioli, Zoltan Pataky, Fabrizio Montecucco, Sebastian Carballo, Aurélien Thomas, Christian Staub, Vincenzo Di Marzo, Gabriella Vincenti, Giuseppe Ambrosio, Osman Ratib, Alain Golay, François Mach, Elisabetta Harsch, Thomas H. Schindler
Journal: JACC. Cardiovascular imaging (2012)
Leber's Hereditary Optic Neuropathy
Authors: Donald R. Johns, Kyle H. Smith, Peter J. Savino, Neil R. Miller
Journal: Ophthalmology (1993)

<b>Background:</b> Leber's hereditary optic neuropathy is associated with four known pathogenetic mutations of mitochondrial DNA (mtDNA) at nucleotide positions (np) 11778, 3460, 15257, and 14484. <b>Methods:</b> The authors collected clinical data from 12 visually symptomatic patients from seven different pedigrees with the 15257 mutation and compared these data with previously published clinical features of the 11778 and 3460 mutations. <b>Results:</b> The authors' results indicate that these three groups of patients are similar in most clinical characteristics evaluated. However, patients with the 15257 mutation are more likely to experience significant recovery of visual acuity than patients with the 11778 mutation (25% versus 4% of eyes; <i>P</i> < 0.001). Patients with the 15257 mutation who also have an associated mutation at np 15812 are less likely to recover vision than those without this association (<i>P</i> = 0.001). Patients with the 15257 mutation also have a higher incidence of spinal cord and peripheral neurologic symptoms (42%) than patients with the other pathogenetic mutations. <b>Conclusions:</b> The phenotypic expression of the 15257 mutation differs from the 11778 and 3460 mutations and is affected by the presence of an associated mutation at np 15812. This is the first clinical evidence to support the concept of multiple simultaneous mtDNA mutations producing additive deleterious effects in patients with Leber's hereditary optic neuropathy. The clinical differences between the various genotypes associated with Leber's hereditary optic neuropathy have implications for risk factor management and visual prognosis and, thus, underscore the importance of molecular genetic testing in patients with suspected Leber's hereditary optic neuropathy.
Lung Carcinoma of Sheep (Jaagsiekte). II. Histogenesis of the Tumor
Authors: K Perk, I Hod, B Presentey, T A Nobel
Journal: JNCI Journal of the National Cancer Institute (1971)

In a study of the sheep lung tumor (Jaagsiekte) different areas of the tumor varied in pathological pattern. Near tumor nodules, neoplastic cells, apparently derived from B-type cells, were observed between normal alveolar epithelial cells. On the edges of the tumor nodules the cells formed adenomatous structures, whereas in central regions, there was intense proliferation of cords, and sheets or nests of anaplastic epithelial cells formed carcinomas, often with a sarcomatous stroma. In large tumor nodes, more differentiated sarcomatous elements covered large areas, giving them a fibrous character. The relationship between the neoplastic cells is discussed. Cytochemical examination revealed that most neoplastic cells contained cytoplasmic glycogen granules; some had phospholipid granules. Many cells contained both types of granules in different proportions. Alkaline phosphatase activity was also detected in many tumor cells. Cytoplasmic inclusion bodies, which different authors have reported to be developmental stages of a viral agent, were found in this study to be cytoplasmic mucin droplets. This finding was substantiated by various cytochemical methods and electron microscopy.
Drug development in IBD: from novel target identification to early clinical trials
Authors: Silvio Danese, Claudio Fiocchi, Julián Panés
Journal: Gut (2016)

The two major forms of IBD, Crohn's disease (CD) and UC, are chronic inflammatory disorders, the pathogenesis of which involves a complex interplay of multiple factors.1 ,2 The introduction of biological agents has substantially expanded and improved the therapeutic options for IBD, but a large proportion of patients still do not respond or achieve remission in the short term or long term. Thus, there is still a considerable need to improve the treatment of IBD, and significant research efforts are underway to address this unmet need.

During the last two decades, the period of time over which the biologics as well as other new drugs for IBD have entered the market, the number of therapies that have failed is remarkably high. This is significant, and understanding the reasons for such failure should lead to a better drug development process and pave the way for alternate and more efficient drug development strategies.

Traditionally, the drug development process initially involves target discovery and selection, and then biological confirmation in cellular and animal models. This is followed by phase I testing in healthy volunteers to check for safety and pharmacokinetics, then phase II testing in patient volunteers to obtain preliminary safety, clinical efficacy and dosing data, and finally phase III clinical studies in patients to obtain a more comprehensive characterisation of the safety and efficacy profile of a drug. This traditional pathway of drug development has had relatively limited success in generating new forms of treatment for IBD. Results have been impacted by predictable high clinical response rates in the placebo groups, a lack of objective end points, trial design with arbitrary definitions of induction and maintenance phases and outcomes, and not taking into account key components of IBD pathogenesis.3 Moreover, a lack of strict criteria to ensure the presence …
Carcinoembryonic Antigen in Nonhuman Primates&lt;xref ref-type="fn" rid="fn2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="fn3"&gt;3&lt;/xref&gt;
Authors: D E Haagensen, R S Metzgar, B Swenson, W G Dilley, C E Cox, S Davis, J Murdoch, N Zamcheck, S A Wells
Journal: JNCI Journal of the National Cancer Institute (1982)

Blood levels of carcinoembryonic antigen (CEA) have been measured in several nonhuman primate species. Only gorillas and chimpanzees were found to have significant elevations of CEA-like activity in their blood compared to the normal values of less than 2.5 ng/ml in humans. The average CEA level in 134 chimpanzees was 25.2 ng/ml (range, 4.2--95 ng/ml) and in 13 gorillas it was 32 ng/ml (range, 12.4--61.9 ng/ml). These levels were not related to sex. Blood levels repeatedly taken over a 1 1/2-year period remained relatively stable in both species. Analysis of parallelism of immunologic reactivity showed chimpanzee CEA to be similar to but not identical with human CEA. The molecular size of chimpanzee CEA was also similar to that of human CEA.
Diaphragmatic Hernia Causing Lung Collapse
Authors: Muhammad Yasin, James C Reed
Journal: New England Journal of Medicine (2016)

A 54-year-old man with a history of cerebral palsy and mental impairment presented with acute respiratory distress. He was afebrile and had a nonproductive cough. Examination revealed an absence of air sounds in the right hemithorax, with audible bowel sounds.
No need to develop a special interest category for emergency general surgery
Authors: W H Allum, Gareth Griffiths, Jon Lund
Journal: BMJ (2016)

We welcome the Nuffield Trust’s contribution to the debate on the provision of emergency general surgery services.1 2 The report comments on the “loss of the generalist”—a surgeon capable of managing patients presenting to an emergency general surgery service by providing the necessary preoperative, intraoperative, and postoperative care.

We …
Self-harm, Unintentional Injury, and Suicide in Bipolar Disorder During Maintenance Mood Stabilizer Treatment
Authors: Joseph F. Hayes, Alexandra Pitman, Louise Marston, Kate Walters, John R. Geddes, Michael King, David P. J. Osborn
Journal: JAMA Psychiatry (2016)

<h3>Importance</h3> Self-harm is a prominent cause of morbidity in patients with bipolar disorder and is strongly associated with suicide. There is evolving evidence that lithium use may reduce suicidal behavior, in addition to concerns that the use of anticonvulsants may increase self-harm. Information is limited about the effects of antipsychotics when used as mood stabilizer treatment. Rates of unintentional injury are poorly defined in bipolar disorder, and understanding drug associations with this outcome may shed light on mechanisms for lithium’s potential antisuicidal properties through reduction in impulsive aggression. <h3>Objective</h3> To compare rates of self-harm, unintentional injury, and suicide in patients with bipolar disorder who were prescribed lithium, valproate sodium, olanzapine, or quetiapine fumarate. <h3>Design, Setting, and Participants</h3> This investigation was a propensity score (PS)–adjusted and PS-matched longitudinal cohort study in a nationally representative UK sample using electronic health records data collected between January 1, 1995, and December 31, 2013. Participants included all patients diagnosed as having bipolar disorder who were prescribed lithium, valproate, olanzapine, or quetiapine as maintenance mood stabilizer treatment. <h3>Main Outcomes and Measures</h3> The primary outcome was any form of self-harm. Secondary outcomes were unintentional injury and suicide. <h3>Results</h3> Of the 14 396 individuals with a diagnosis of BPD, 6671 were included in the cohort, with 2148 prescribed lithium, 1670 prescribed valproate, 1477 prescribed olanzapine, and 1376 prescribed quetiapine as maintenance mood stabilizer treatment. Self-harm rates were lower in patients prescribed lithium (205; 95% CI, 175-241 per 10 000 person-years at risk [PYAR]) compared with those prescribed valproate (392; 95% CI, 334-460 per 10 000 PYAR), olanzapine (409; 95% CI, 345-483 per 10 000 PYAR), or quetiapine (582; 95% CI, 489-692 per 10 000 PYAR). This association was maintained after PS adjustment (hazard ratio [HR], 1.40; 95% CI, 1.12-1.74 for valproate, olanzapine, or quetiapine vs lithium) and PS matching (HR, 1.51; 95% CI, 1.21-1.88). After PS adjustment, unintentional injury rates were lower for lithium compared with valproate (HR, 1.32; 95% CI, 1.10-1.58) and quetiapine (HR, 1.34; 95% CI, 1.07-1.69) but not olanzapine. The suicide rate in the cohort was 14 (95% CI, 9-21) per 10 000 PYAR. Although this rate was lower in the lithium group than for other treatments, there were too few events to allow accurate estimates. <h3>Conclusions and Relevance</h3> Patients taking lithium had reduced self-harm and unintentional injury rates. This finding augments limited trial and smaller observational study results. It supports the hypothesis that lithium use reduces impulsive aggression in addition to stabilizing mood.
Defective postreperfusion metabolic recovery directly associates with incident delayed graft function
Authors: Leonie G.M. Wijermars, Alexander F. Schaapherder, Dorottya K. de Vries, Lars Verschuren, Rob C.I. Wüst, Sarantos Kostidis, Oleg A. Mayboroda, Frans Prins, Jan Ringers, Jörgen Bierau, Jaap A. Bakker, Teake Kooistra, Jan H.N. Lindeman
Journal: Kidney International (2016)
Congenital Heart Disease--II
Authors: M. Campbell
Journal: BMJ (1950)

Cyanotic Heart DiseaseDiagnosis has recently become of great practical importance in the cyanotic group because of the enormous help that can be given to many of these children by a gubclavianpulmonary anastomosis or other surgical treatment.Without this the outlook is poor for most of these patients; this is strongly supported by the age incidence of the first 340 cases seen in 1947-8, as it shows a steeply dimi- nishing curve.Age 0-2 years 3-5 ,, 6-8 , 9-11 ,, 12-14 , No. Age .
How to define pulmonary hypertension due to left heart disease
Authors: Mario Gerges, Christian Gerges, Irene M. Lang
Journal: European Respiratory Journal (2016)

Current 2015 European Society of Cardiology (ESC)/European Respiratory Society (ERS) guidelines for the diagnosis and treatment of pulmonary hypertension (PH) [1, 2] have adopted new insights in the understanding of PH due to left heart disease (PH-LHD, group 2). Pulmonary vascular disease in heart failure comprises increased RV afterload, poor RV-PV coupling and worse survival <http://ow.ly/4n622h>
Rebooting the microbiome
Authors: Sean Munoz, Mabel Guzman-Rodriguez, Jun Sun, Yong-Guo Zhang, Curtis Noordhof, Shu-Mei He, Emma Allen-Vercoe, Erika C Claud, Elaine O Petrof
Journal: Gut Microbes (2016)

Using a murine Salmonella model of colitis, we recently reported that mice receiving a community of defined gut microbiota (MET-1) lost less weight, had reduced systemic inflammation and splenic S. typhimurium infection, and decreased neutrophil infiltration in the cecum, compared to vehicle controls. In addition, animals receiving MET-1 exhibited preserved tight junction protein expression (Zonula occludens-1, claudin-1), suggesting important effects on barrier function. In this addendum, we describe additional in vitro experiments examining effects of MET-1, as well as in vivo experiments demonstrating that MET-1 is protective in a DSS model of colitis after administration of antibiotics. Placed in the context of our findings and those of others, we discuss differences in our findings between the Salmonella colitis and DSS colitis models, provide speculation as to which bacteria may be important in the protective effects of MET-1, and discuss potential implications for other GI diseases such as IBD.
Confirmed moisture damage may induce systemic inflammation in children
Authors: Juha Pekkanen, Kirsi Mustonen, Anne Karvonen, Pirkka Kirjavainen, Marjut Roponen, Petra Pfefferl, Jon Genuneit, Erika von Mutius, Anne Hyvärinen
Journal: European Respiratory Journal (2014)

Several studies have shown that moisture damage and mold are associated with increased risk of respiratory symptoms and asthma but the mechanisms mediating these effects are still unknown.   Aims:  To study in a cross-sectional analysis, if confirmed moisture damage in homes could induce systemic subclinical inflammation in 6-year-old children.   Methods:  Technical inspections were performed in homes of 307 children aged 6 years. Blood samples were collected for determination of C-reactive protein (CRP), 24-hour PI and LPS stimulated and non-stimulated proinflammatory cytokines (IL-1b, TNF, IL-6) and leucocyte counts. Fractional exhaled nitric oxide (FeNO) was measured and parents filled in a questionnaire.   Results:  No associations of indicators of moisture damage or mold in any area of the house were observed with levels of CRP, blood leucocyte counts or FeNO, or with respiratory symptoms or infections. In contrast, there were consistently positive associations with proinflammatory cytokines, especially IL-1b and TNF. Associations were most consistent for visible mold in the bathroom, which was significantly associated with non-stimulated and PI-stimulated IL-1b and TNF, and with PI-stimulated IL-6.   Conclusions:  Moisture damage and mold at home at the age of 6 years were associated with increased levels and production of proinflammatory cytokines, but not with respiratory symptoms or other markers of inflammation. Our study suggests that moisture damage or mold at home may have an effect on proinflammatory cytokines even without an effect on respiratory symptoms.
Patterns of Growth and Decline in Lung Function in Persistent Childhood Asthma
Authors: Michael J. McGeachie, Katherine P. Yates, Xiaobo Zhou, Feng Guo, Alice L. Sternberg, Mark L. Van Natta, Robert A. Wise, Stanley J. Szefler, Sunita Sharma, Alvin T. Kho, Michael H. Cho, Damien C. Croteau-Chonka, Peter J. Castaldi, Gaurav Jain, Amartya Sanyal, Ye Zhan, Bryan R. Lajoie, Job Dekker, John Stamatoyannopoulos, Ronina A. Covar, Robert S. Zeiger, N. Franklin Adkinson, Paul V. Williams, H. William Kelly, Hartmut Grasemann, Judith M. Vonk, Gerard H. Koppelman, Dirkje S. Postma, Benjamin A. Raby, Isaac Houston, Quan Lu, Anne L. Fuhlbrigge, Kelan G. Tantisira, Edwin K. Silverman, James Tonascia, Scott T. Weiss, Robert C. Strunk
Journal: New England Journal of Medicine (2016)

Tracking longitudinal measurements of growth and decline in lung function in patients with persistent childhood asthma may reveal links between asthma and subsequent chronic airflow obstruction.