tbuckley/cabot-search huggingface dataset:
Paternal Metabolic and Cardiovascular Risk Factors for Fetal Growth Restriction
Authors: Sara Hillman, Donald M. Peebles, David J. Williams
Journal: Diabetes Care (2013)

Fathers of low-birth weight offspring are more likely to have type 2 diabetes and cardiovascular disease in later life. We investigated whether paternal insulin resistance and cardiovascular risk factors were evident at the time that fetal growth-restricted offspring were born.We carried out a case-control study of men who fathered pregnancies affected by fetal growth restriction, in the absence of recognized fetal disease (n = 42), compared with men who fathered normal-birth weight offspring (n = 77). All mothers were healthy, nonsmoking, and similar in age, BMI, ethnicity, and parity. Within 4 weeks of offspring birth, all fathers had measures of insulin resistance (HOMA index), blood pressure, waist circumference, endothelial function (flow-mediated dilatation), lipid profile, weight, and smoking habit. Comparison was made using multivariable logistical regression analysis.Fathers of fetal growth-restricted offspring [mean (SD) 1.8th (2.2) customized birth centile] were more likely to have insulin resistance, hypertension, central adiposity, and endothelial dysfunction and to smoke cigarettes compared with fathers of normal grown offspring. After multivariable analysis, paternal insulin resistance and smoking remained different between the groups. Compared with fathers of normal grown offspring, men who fathered pregnancies affected by fetal growth restriction had an OR 7.68 (95% CI 2.63-22.40; P < 0.0001) of having a 1-unit higher log HOMA-IR value and 3.39 (1.26-9.16; P = 0.016) of being a smoker.Men who recently fathered growth-restricted offspring have preclinical evidence of the insulin resistance syndrome and are more likely to smoke than fathers of normal grown offspring. Paternal lifestyle may influence heritable factors important for fetal growth.
Topographical Continuity of Bacterial Populations in the Healthy Human Respiratory Tract
Authors: Emily S. Charlson, Kyle Bittinger, Andrew R. Haas, Ayannah S. Fitzgerald, Ian Frank, Anjana Yadav, Frederic D. Bushman, Ronald G. Collman
Journal: American Journal of Respiratory and Critical Care Medicine (2011)

Defining the biogeography of bacterial populations in human body habitats is a high priority for understanding microbial-host relationships in health and disease. The healthy lung was traditionally considered sterile, but this notion has been challenged by emerging molecular approaches that enable comprehensive examination of microbial communities. However, studies of the lung are challenging due to difficulties in working with low biomass samples.Our goal was to use molecular methods to define the bacterial microbiota present in the lungs of healthy individuals and assess its relationship to upper airway populations.We sampled respiratory flora intensively at multiple sites in six healthy individuals. The upper tract was sampled by oral wash and oro-/nasopharyngeal swabs. Two bronchoscopes were used to collect samples up to the glottis, followed by serial bronchoalveolar lavage and lower airway protected brush. Bacterial abundance and composition were analyzed by 16S rDNA Q-PCR and deep sequencing.Bacterial communities from the lung displayed composition indistinguishable from the upper airways, but were 2 to 4 logs lower in biomass. Lung-specific sequences were rare and not shared among individuals. There was no unique lung microbiome.In contrast to other organ systems, the respiratory tract harbors a homogenous microbiota that decreases in biomass from upper to lower tract. The healthy lung does not contain a consistent distinct microbiome, but instead contains low levels of bacterial sequences largely indistinguishable from upper respiratory flora. These findings establish baseline data for healthy subjects and sampling approaches for sequence-based analysis of diseases.
TEN AMINO ACIDS ESSENTIAL FOR PLASMA PROTEIN PRODUCTION EFFECTIVE ORALLY OR INTRAVENOUSLY
Authors: S. C. Madden, J. R. Carter, A. A. Kattus, L. L. Miller, G. H. Whipple
Journal: The Journal of Experimental Medicine (1943)

When blood plasma proteins are depleted by bleeding with return of the washed red cells (plasmapheresis) it is possible to bring dogs to a steady state of hypoproteinemia and a constant level of plasma protein production if the diet protein intake is controlled and limited. Such dogs are outwardly normal but have a lowered resistance to infection and to certain intoxications. When the protein intake of such dogs is completely replaced by the growth mixture (Rose) of crystalline amino acids, plasma protein production is excellent, weight and nitrogen balance are maintained. This growth mixture consists of ten amino acids, threonine, valine, leucine, isoleucine, tryptophane, lysine, phenylalanine, methionine, histidine, arginine, and is as effective as most diet proteins in plasma protein production. The above amino acid mixture in aqueous solution may be given by vein with equally good plasma protein production and no apparent clinical disturbance even when given rapidly. Cystine may replace methionine in the above mixture with equally good plasma protein production for 7 to 10 days but at the expense of the body tissues, that is, with weight loss and a negative nitrogen balance. The addition of cystine to the protein-free, otherwise adequate diet may result in the production of considerable new plasma protein during a period as long as 1 week (cystine effect). This reaction may depend upon the amino acid constitution of the preceding diet protein in that it occurred following a liver feeding but did not occur after pancreas feeding. Arginine is required in the diet of the protein depleted dog for fabrication of plasma protein. It is apparently not needed for nitrogen balance for as long as 1 or 2 weeks. The omission of either threonine or valine from the growth mixture is quickly followed by a sharp decline in plasma protein formation and by a negative nitrogen balance. When histidine, arginine, and most of the lysine are omitted from the growth mixture, nitrogen balance and weight may be maintained for as long as 1 week but plasma protein production falls off markedly. The findings indicate that the growth mixture of amino acids should be a valuable addition to transfusion and infusion therapy in disease states associated with deficient nitrogen intake or tissue injury and accelerated nitrogen loss, including shock, burns, and major operative procedures.
Risk for gastric cancer in people with CagA positive or CagA negative Helicobacter pylori infection.
Authors: J Parsonnet, G D Friedman, N Orentreich, H Vogelman
Journal: Gut (1997)

BACKGROUND AND AIMS: It is not known why some people with Helicobacter pylori infection develop gastric cancer whereas others do not. Whether the CagA phenotype of H pylori infection affected risk for cancer independently of other posited risk factors was evaluated. SUBJECTS: 242 persons who participated in a previous nested case-control study of gastric cancer. 179 (90 cases and 89 controls) were infected with H pylori as determined by enzyme linked immunosorbent assay (ELISA) in serum and 63 (13 cases and 50 controls) were uninfected. METHODS: Serum samples from cases and controls, obtained a mean of 14.2 years before diagnosis of cancer in the cases, were tested by ELISA for IgG antibodies against the CagA gene product of H pylori. They had previously been tested for pepsinogen I. Using logistic regression analysis, risk for cancer was compared among infected persons with CagA antibodies, infected persons without CagA antibodies, and uninfected persons. RESULTS: Subjects infected with H pylori who had CagA antibodies were 5.8-fold more likely than uninfected subjects to develop gastric cancer (95% confidence interval (95% CI) = 2.6-13.0). This was true for both intestinal (odds ratio (OR) 5.1, 95% CI = 2.1-12.2) and diffuse type (OR 10.1, 95% CI = 2.2-47.4) cancers. By contrast, H pylori infected subjects without CagA antibodies were only slightly, and not significantly, at increased risk for cancer (OR 2.2, 95% CI = 0.9-5.4) and any possible association was restricted to diffuse type carcinoma (OR 9.0, 95% CI = 1.2-65.8). Pepsinogen 1 &lt; 50 ng/ml significantly increased risk for both cancer types in H pylori infected persons and lessened the magnitude of association between CagA and cancer. Educational attainment, cigarette smoking, and ABO blood group were not associated with malignancy. CONCLUSIONS: When compared with uninfected subjects, persons infected with CagA positive H pylori are at considerably increased risk of gastric cancer. CagA negative H pylori are less strongly linked to malignancy and may only be associated with diffuse type disease.
Rituals are rational for the imperfect experimentalist
Authors: M. D. Rutherford
Journal: Behavioral and Brain Sciences (2006)

Humans are, by design, imperfect experimentalists. The cost of testing each step of a process exceeds the benefit of knowing which steps can be eliminated. To an outsider who knows which steps are superfluous, the actors appear superstitious, even ridiculous. Nonetheless, the exact duplication of all steps is rational for the imperfect experimentalist. The case of ritual in autism illustrates this point.
Primate-Specific miR-663 Functions as a Tumor Suppressor by Targeting <i>PIK3CD</i> and Predicts the Prognosis of Human Glioblastoma
Authors: Yu Shi, Cong Chen, Xia Zhang, Qing Liu, Jin-Ling Xu, Hua-Rong Zhang, Xiao-Hong Yao, Tao Jiang, Zhi-Cheng He, Yong Ren, Wei Cui, Chuan Xu, Ling Liu, You-Hong Cui, Shi-Zhu Yu, Yi-Fang Ping, Xiu-Wu Bian
Journal: Clinical Cancer Research (2014)

To determine the prognostic significance of miR-663 in glioblastoma, its effect in tumor progression, and the underlying mechanism.Specimens from 256 cases of patients with glioma, including 239 patients with follow-up information, were used to analyze the association between miR-663 and patients' prognosis by Kaplan-Meier and multivariate Cox regression analyses. The effects of miR-663 on glioblastoma cell proliferation and invasion were examined both in vitro and in vivo. Bioinformatics prediction and signal network analysis were applied to identify the putative targets of miR-663, which were further verified by luciferase reporter assay, rescue experiments as well as the immunohistochemistry (IHC) and Western blotting examination of downstream effectors. Quantitative reverse transcriptase PCR (qRT-PCR) and IHC were applied to investigate the clinical association between miR-663 and its target in human glioblastoma specimens.miR-663 was inversely correlated with glioma grades but positively correlated with patients' survival. Furthermore, two distinct subgroups of patients with glioblastoma with different prognoses were identified on the basis of miR-663 expression in our specimens and that from The Cancer Genome Atlas (TCGA) database. Overexpression of miR-663 significantly suppressed the proliferation and invasion of glioblastoma cells in vitro and in vivo. Mechanistically, we discovered PIK3CD as a direct target of miR-663 and found that phosphorylated AKT and three key downstream effectors of PIK3CD, i.e., CCND1, MMP2, and MMP7, were downregulated by miR-663 overexpression. Moreover, PIK3CD was inversely correlated with miR-663 in glioblastoma specimens and predicted poor prognosis of patients with glioblastoma.miR-663 is a novel prognostic biomarker and a potential therapeutic candidate for glioblastoma.
Extracellular matrix distribution and hillock formation in human mesangial cells in culture without serum.
Authors: W F Glass, P R Teng, L B Haney
Journal: Journal of the American Society of Nephrology (1996)

Smooth muscle cell and mesangial cell hillock formation have been proposed as in vitro models of vascular sclerosis and glomerular sclerosis. This growth pattern is characterized by multilayered ridges and nodules, termed hills or hillocks, separated by less populated areas termed valleys. In this study, it was discovered that an extracellular matrix rich in pericellular fibronectin-fibrils was key to hillock formation. Human mesangial cells were plated onto serum-coated or noncoated substrata in serum-free medium. Subconfluent cells on serum-coated substrata migrated together, forming aggregates, but cells on noncoated substrata remained evenly dispersed. When plated at confluent densities, cells in serum-coated dishes formed hillocks, but cells in noncoated dishes did not. In serum-coated dishes, the substratum underlying subconfluent cells was vitronectin-rich but fibronectin-poor, whereas the pericellular matrix contained abundant fibronectin fibrils. In contrast, the substratum of subconfluent cells plated in noncoated dishes lacked vitronectin but was fibronectin-rich, whereas the pericellular matrix contained few fibronectin fibrils. The distributions of integrin receptors for fibronectin (rabbit anti-alpha 5 beta 1) and vitronectin (rabbit anti-alpha V, beta 3, and beta 5) followed the distributions of their ligands, fibronectin and vitronectin, respectively. Antibodies to fibronectin blocked hillock formation by cells on serum-coated substrata and prevented spreading of cells on noncoated substrata. In summary, key steps in hillock formation are: (1) migration, (2) secretion of fibronectin and assembly of pericellular fibrils, (3) fibronectin fibril-mediated cell-cell adhesion, and (4) aggregation of cells with further migration to form multiple layers. A similar mechanism may play a role in vascular and glomerular sclerosis.
Leading cancer hospital resumes some services after major fire
Authors: Adrian O’Dowd
Journal: BMJ (2008)

Some services for cancer patients at London’s world famous Royal Marsden NHS Foundation Trust have resumed this week after a large fire destroyed much of the roof and upper floors in the early afternoon of 2 January. But the trust said it would take months to repair, rebuild, and refurbish the hospital completely.

The Royal Marsden was the first hospital in the world to be dedicated to cancer treatment and research, and sees more than 40 000 patients every year.

Around 25 fire engines attended the fire and 120 …
Subunit 6 of the COP9 signalosome promotes tumorigenesis in mice through stabilization of MDM2 and is upregulated in human cancers
Authors: Ruiying Zhao, Sai-Ching J. Yeung, Jian Chen, Tomoo Iwakuma, Chun-Hui Su, Bo Chen, Changju Qu, Fanmao Zhang, You-Tzung Chen, Yu-Li Lin, Dung-Fang Lee, Feng Jin, Rui Zhu, Tattym Shaikenov, Dos Sarbassov, Aysegul Sahin, Huamin Wang, Hua Wang, Chien-Chen Lai, Fuu-Jen Tsai, Guillermina Lozano, Mong-Hong Lee
Journal: Journal of Clinical Investigation (2011)

The mammalian constitutive photomorphogenesis 9 (COP9) signalosome (CSN), a protein complex involved in embryonic development, is implicated in cell cycle regulation and the DNA damage response. Its role in tumor development, however, remains unclear. Here, we have shown that the COP9 subunit 6 (CSN6) gene is amplified in human breast cancer specimens, and the CSN6 protein is upregulated in human breast and thyroid tumors. CSN6 expression positively correlated with expression of murine double minute 2 (MDM2), a potent negative regulator of the p53 tumor suppressor. Expression of CSN6 appeared to prevent MDM2 autoubiquitination at lysine 364, resulting in stabilization of MDM2 and degradation of p53. Mice in which Csn6 was deleted died early in embryogenesis (E7.5). Embryos lacking both Csn6 and p53 survived to later in embryonic development (E10.5), which suggests that loss of p53 could partially rescue the effect of loss of Csn6. Mice heterozygous for Csn6 were sensitized to γ-irradiation–induced, p53-dependent apoptosis in both the thymus and the developing CNS. These mice were also less susceptible than wild-type mice to γ-irradiation–induced tumorigenesis. These results suggest that loss of CSN6 enhances p53-mediated tumor suppression in vivo and that CSN6 plays an important role in regulating DNA damage–associated apoptosis and tumorigenesis through control of the MDM2-p53 signaling pathway.
Borderline Personality Disorder in Clinical Practice
Authors: Carolyn Zittel Conklin, Drew Westen
Journal: American Journal of Psychiatry (2005)

Most studies of borderline personality disorder have drawn patients from among hospital inpatients or outpatients. The aims of this study were to examine the nature of borderline personality disorder patients in everyday clinical practice and to use data from a sample of borderline personality disorder patients seen in the community to refine the borderline construct.A random national sample of 117 experienced psychiatrists and psychologists from the membership registers of the American Psychiatric Association and American Psychological Association provided data on a randomly selected patient with borderline personality disorder (N=90) or dysthymic disorder (N=27) from their practice. The clinicians provided data on axis I comorbidity, axis II comorbidity, and adaptive functioning, as well as a personality description of the patient using the Shedler-Westen Assessment Procedure-200 (SWAP-200) Q-sort, an instrument designed for assessment and taxonomic purposes. Analyses compared borderline personality disorder and dysthymic disorder groups on variables of interest and aggregated SWAP-200 items across all borderline personality disorder patients to create a composite portrait of borderline personality disorder as seen in the community.The borderline personality disorder sample strongly resembled previously studied borderline personality disorder samples with regard to comorbidity and adaptive functioning. However, the SWAP-200 painted a portrait of borderline personality disorder patients as having more distress and emotion dysregulation, compared to the DSM-IV description.Borderline personality disorder patients in research samples are highly similar to those seen in a cross-section of clinical practice. However, several studies have now replicated a portrait of borderline personality disorder symptoms that places greater weight than the DSM-IV description on the intense psychological pain of these patients and suggests candidate diagnostic criteria for DSM-V.
Toll-like Receptors in Tumor Immunotherapy
Authors: Chrystal M. Paulos, Andrew Kaiser, Claudia Wrzesinski, Christian S. Hinrichs, Lydie Cassard, Andrea Boni, Pawel Muranski, Luis Sanchez-Perez, Douglas C. Palmer, Zhiya Yu, Paul A. Antony, Luca Gattinoni, Steven A. Rosenberg, Nicholas P. Restifo
Journal: Clinical Cancer Research (2007)

Abstract Lymphodepletion with chemotherapeutic agents or total body irradiation (TBI) before adoptive transfer of tumor-specific T cells is a critical advancement in the treatment of patients with melanoma. More than 50% of patients that are refractory to other treatments experience an objective or curative response with this approach. Emerging data indicate that the key mechanisms underlying how TBI augments the functions of adoptively transferred T cells include (a) the depletion of regulatory T cells (Treg) and myeloid-derived suppressor cells that limit the function and proliferation of adoptively transferred cells; (b) the removal of immune cells that act as “sinks” for homeostatic cytokines, whose levels increase after lymphodepletion; and (c) the activation of the innate immune system via Toll-like receptor 4 signaling, which is engaged by microbial lipopolysaccharide that translocated across the radiation-injured gut. Here, we review these mechanisms and focus on the effect of Toll-like receptor agonists in adoptive immunotherapy. We also discuss alternate regimens to chemotherapy or TBI, which might be used to safely treat patients with advanced disease and promote tumor regression.
Are prolific authors too much of a good thing?
Authors: Elizabeth Wager
Journal: BMJ (2015)

Dominant authors can lead to an imbalance of power within an evidence base

According to a linked article by Holleman and colleagues,1 diabetes research is dominated by a few dozen prolific researchers, a handful so productive that they were designated “supertrialists.” Holleman and colleagues examined randomised controlled trials of glucose lowering drugs published in the 20 years up to 2013, and found that roughly a third (32.4%) of reports were published by less than 1% (110 of 13 592) of authors. The most prolific individuals were named on seven trial reports, on average, every year for the last 10 years. Holleman and colleagues’ study did not determine how many separate trials were reported by these articles, but even assuming that large trials generate several publications, they found that some authors had an extraordinary output. In a similar study of prolific authors,2 the 10 most productive in each of four medical specialties were named on at least one publication per 10 working days each year, showing that the issue is not restricted to diabetes research.

Making a meaningful contribution to both the research and publication processes, as required by authorship criteria from the International Committee of Medical Journal …
Mycobacterium tuberculosis Infection in Health Care Workers in Rural India
Authors: Madhukar Pai, Kaustubh Gokhale, Rajnish Joshi, Sandeep Dogra, Shriprakash Kalantri, Deepak K. Mendiratta, Pratibha Narang, Charles L. Daley, Reuben M. Granich, Gerald H. Mazurek, Arthur L. Reingold, Lee W. Riley, John M. Colford
Journal: JAMA (2005)

Mycobacterium tuberculosis infection in health care workers has not been adequately studied in developing countries using newer diagnostic tests.To estimate latent tuberculosis infection prevalence in health care workers using the tuberculin skin test (TST) and a whole-blood interferon gamma (IFN-gamma) assay; to determine agreement between the tests; and to compare their correlation with risk factors.A cross-sectional comparison study of 726 health care workers aged 18 to 61 years (median age, 22 years) with no history of active tuberculosis conducted from January to May 2004, at a rural medical school in India. A total of 493 (68%) of the health care workers had direct contact with patients with tuberculosis and 514 (71%) had BCG vaccine scars.Tuberculin skin testing was performed using 1-TU dose of purified protein derivative RT23, and the IFN-gamma assay was performed by measuring IFN-gamma response to early secreted antigenic target 6, culture filtrate protein 10, and a portion of tuberculosis antigen TB7.7.Agreement between TST and the IFN-gamma assay, and comparison of the tests with respect to their association with risk factors.A large proportion of the health care workers were latently infected; 360 (50%) were positive by either TST or IFN-gamma assay, and 226 (31%) were positive by both tests. The prevalence estimates of TST and IFN-gamma assay positivity were comparable (41%; 95% confidence interval [CI], 38%-45% and 40%; 95% CI, 37%-43%, respectively). Agreement between the tests was high (81.4%; kappa = 0.61; 95% CI, 0.56-0.67). Increasing age and years in the health profession were significant risk factors for both IFN-gamma assay and TST positivity. BCG vaccination had little impact on TST and IFN-gamma assay results.Our study showed high latent tuberculosis infection prevalence in Indian health care workers, high agreement between TST and IFN-gamma assay, and similar association between positive test results and risk factors. Although TST and IFN-gamma assay appear comparable in this population, they have different performance and operational characteristics; therefore, the decision to select one test over the other will depend on the population, purpose of testing, and resource availability.
Glucocorticoid Induced Leucine Zipper Mediates the Anti-Inflammatory Effects of Dexamethasone in Airway Epithelial Cells
Authors: J. Eddleston, J. Herschbach, A.L. Wagelie-Steffen, S.C. Christiansen, B.L. Zuraw
Journal: Journal of Allergy and Clinical Immunology (2007)