tbuckley/cabot-search huggingface dataset:
Psychiatric Disorders From Childhood to Adulthood in 22q11.2 Deletion Syndrome: Results From the International Consortium on Brain and Behavior in 22q11.2 Deletion Syndrome
Authors: Maude Schneider, Martin Debbané, Anne S. Bassett, Eva W.C. Chow, Wai Lun Alan Fung, Marianne B.M. van den Bree, Michael Owen, Kieran C. Murphy, Maria Niarchou, Wendy R. Kates, Kevin M. Antshel, Wanda Fremont, Donna M. McDonald-McGinn, Raquel E. Gur, Elaine H. Zackai, Jacob Vorstman, Sasja N. Duijff, Petra W.J. Klaassen, Ann Swillen, Doron Gothelf, Tamar Green, Abraham Weizman, Therese Van Amelsvoort, Laurens Evers, Erik Boot, Vandana Shashi, Stephen R. Hooper, Carrie E. Bearden, Maria Jalbrzikowski, Marco Armando, Stefano Vicari, Declan G. Murphy, Opal Ousley, Linda E. Campbell, Tony J. Simon, Stephan Eliez
Journal: American Journal of Psychiatry (2014)

Objective Chromosome 22q11.2 deletion syndrome is a neurogenetic disorder associated with high rates of schizophrenia and other psychiatric conditions. The authors report what is to their knowledge the first large-scale collaborative study of rates and sex distributions of psychiatric disorders from childhood to adulthood in 22q11.2 deletion syndrome. The associations among psychopathology, intellect, and functioning were examined in a subgroup of participants. Method The 1,402 participants with 22q11.2 deletion syndrome, ages 6–68 years, were assessed for psychiatric disorders with validated diagnostic instruments. Data on intelligence and adaptive functioning were available for 183 participants ages 6 to 24 years. Results Attention deficit hyperactivity disorder (ADHD) was the most frequent disorder in children (37.10%) and was overrepresented in males. Anxiety disorders were more prevalent than mood disorders at all ages, but especially in children and adolescents. Anxiety and unipolar mood disorders were overrepresented in females. Psychotic disorders were present in 41% of adults over age 25. Males did not predominate in psychotic or autism spectrum disorders. Hierarchical regressions in the subgroup revealed that daily living skills were predicted by the presence of anxiety disorders. Psychopathology was not associated with communication or socialization skills. Conclusions To the authors’ knowledge, this is the largest study of psychiatric morbidity in 22q11.2 deletion syndrome. It validates previous findings that this condition is one of the strongest risk factors for psychosis. Anxiety and developmental disorders were also prevalent. These results highlight the need to monitor and reduce the long-term burden of psychopathology in 22q11.2 deletion syndrome.
Evaluation of how different implementation strategies of an injury prevention programme (FIFA 11+) impact team adherence and injury risk in Canadian female youth football players: a cluster-randomised trial
Authors: Kathrin Steffen, Willem H Meeuwisse, Maria Romiti, Jian Kang, Carly McKay, Mario Bizzini, Jiri Dvorak, Caroline Finch, Grethe Myklebust, Carolyn A Emery
Journal: British Journal of Sports Medicine (2013)

Background Injury prevention programme delivery on adherence and injury risk, specifically involving regular supervisions with coaches and players on programme execution on field, has not been examined. Aim The objective of this cluster-randomised study was to evaluate different delivery methods of an effective injury prevention programme (FIFA 11+) on adherence and injury risk among female youth football teams. Method During the 4-month 2011 football season, coaches and 13-year-old to 18-year-old players from 31 tier 1–3 level teams were introduced to the 11+ through either an unsupervised website (‘control’) or a coach-focused workshop with (‘comprehensive’) and without (‘regular’) additional supervisions by a physiotherapist. Team and player adherence to the 11+, playing exposure, history and injuries were recorded. Results Teams in the comprehensive and regular intervention groups demonstrated adherence to the 11+ programme of 85.6% and 81.3% completion of total possible sessions, compared to 73.5% for teams in the control group. These differences were not statistically significant, after adjustment for cluster by team, age, level and injury history. Compared to players with low adherence, players with high adherence to the 11+ had a 57% lower injury risk (IRR 0.43, 95% CI 0.19 to 1.00). However, adjusting for covariates, this between-group difference was not statistically significant (IRR=0.44, 95% CI 0.18 to 1.06). Conclusion Following a coach workshop, coach-led delivery of the FIFA 11+ was equally successful with or without the additional field involvement of a physiotherapist. Proper education of coaches during an extensive preseason workshop was more effective in terms of team adherence than an unsupervised delivery of the 11+ programme to the team. Trial registration ISRCTN67835569.
Radionuclide Venography in the Evaluation of Superior Vena Cava Syndrome
Authors: P VAN HOUTTE, J FR??HLING
Journal: Clinical Nuclear Medicine (1981)

Isotopic phlebography with Tc-99m-labeled microspheres was performed in 55 patients, 22 of whom presented with superior vena cava syndrome. The localization of the venous obstruction was visualized in each case, along with associated collateral views. Moreover, the transit times at different levels were markedly increased. In 11 patients, isotopic phlebography was repeated following treatment. Improvement, when it occurred, was largely due to diminished obstruction of the superior vena cava rather than to increased collateral supply. Therefore, isotopic phlebography of the upper extremities is a useful tool for the diagnosis of superior vena cava syndrome and for the evaluation of response to treatment.
Airway Inflammation in Severe Chronic Obstructive Pulmonary Disease
Authors: Graziella Turato, Renzo Zuin, Massimo Miniati, Simonetta Baraldo, Federico Rea, Bianca Beghé, Simonetta Monti, Bruno Formichi, Piera Boschetto, Sergio Harari, Alberto Papi, Piero Maestrelli, Leonardo M. Fabbri, Marina Saetta
Journal: American Journal of Respiratory and Critical Care Medicine (2002)

The lung pathology of severe chronic obstructive pulmonary disease (COPD) has been poorly investigated. We examined surgical specimens obtained from patients with severe (forced expiratory volume in 1 second [FEV1] = 29 ± 3% predicted, n = 9) or mild/no airflow limitation (FEV1 = 86 ± 5% predicted, n = 9) and similar smoking history. With histochemical and immunohistochemical methods we quantified the structural changes and the inflammatory cells in small airways and in muscular pulmonary arteries. As compared with smokers with mild/no COPD, smokers with severe COPD had an increased number of leukocytes in the small airways, which showed a positive correlation with the radiologic score of emphysema and with the value of residual volume, and a negative correlation with the values of FEV1 and carbon monoxide diffusing capacity. The inflammatory process was characterized by an increase in CD8+ and CD4+ T-lymphocytes in the airway wall and by an increase in macrophages in the airway epithelium. When all smokers were considered together, the smoking history was correlated with both the airway wall and smooth muscle thickness, suggesting that smoking itself may play a role in the development of structural changes. No structural and cellular differences were observed in pulmonary arteries between smokers with severe COPD and smokers with mild/no COPD. In conclusion, in the small airways of smokers with severe COPD, there is an increased number of leukocytes, which is correlated with reduced expiratory flow, lung hyperinflation, carbon monoxide diffusion impairment, and radiologic emphysema, suggesting a role for this inflammatory response in the clinical progression of the disease.
Lateral epicondylitis in tennis: update on aetiology, biomechanics and treatment
Authors: Thomas De Smedt, Andy de Jong, Wim Van Leemput, Dossche Lieven, Francis Van Glabbeek
Journal: British Journal of Sports Medicine (2007)

Lateral epicondylitis (tennis elbow) is the most frequent type of myotendinosis and can be responsible for substantial pain and loss of function of the affected limb. Tennis biomechanics, player characteristics and equipment are important in preventing the condition. This article presents an overview of the current knowledge on lateral epicondylitis, and focuses on treatment strategies. Conservative and surgical treatment options are discussed, and recent techniques are outlined.
Estimated Average Glucose and Self-Monitored Mean Blood Glucose Are Discordant Estimates of Glycemic Control
Authors: James M. Hempe, Arlette A. Soros, Stuart A. Chalew
Journal: Diabetes Care (2010)

The A1C-Derived Average Glucose study recommended reporting A1C in estimated average glucose (eAG) equivalents. We compared eAG with self-monitored mean blood glucose (MBG) to determine whether eAG is systematically biased due to biological variation in the relationship between MBG and A1C.
TCR stimulation with modified anti-CD3 mAb expands CD8+ T cell population and induces CD8+CD25+ Tregs
Authors: Brygida Bisikirska, John Colgan, Jeremy Luban, Jeffrey A. Bluestone, Kevan C. Herold
Journal: Journal of Clinical Investigation (2005)

Modified anti-CD3 mAbs are emerging as a possible means of inducing immunologic tolerance in settings including transplantation and autoimmunity such as in type 1 diabetes. In a trial of a modified anti-CD3 mAb [hOKT3gamma1(Ala-Ala)] in patients with type 1 diabetes, we identified clinical responders by an increase in the number of peripheral blood CD8+ cells following treatment with the mAb. Here we show that the anti-CD3 mAb caused activation of CD8+ T cells that was similar in vitro and in vivo and induced regulatory CD8+CD25+ T cells. These cells inhibited the responses of CD4+ cells to the mAb itself and to antigen. The regulatory CD8+CD25+ cells were CTLA4 and Foxp3 and required contact for inhibition. Foxp3 was also induced on CD8+ T cells in patients during mAb treatment, which suggests a potential mechanism of the anti-CD3 mAb immune modulatory effects involving induction of a subset of regulatory CD8+ T cells.
A Functional Role for KLF6-SV1 in Lung Adenocarcinoma Prognosis and Chemotherapy Response
Authors: Analisa DiFeo, Lauren Feld, Estefania Rodriguez, Christine Wang, David G. Beer, John A. Martignetti, Goutham Narla
Journal: Cancer Research (2008)

Kruppel-like factor 6 (KLF6) is a tumor suppressor gene that is functionally inactivated in human cancer by loss of heterozygosity, somatic mutation, decreased expression, and increased alternative splicing into an oncogenic splice variant, KLF6-SV1. Here we show that increased expression of KLF6-SV1 is associated with decreased survival in patients with lung adenocarcinoma. In addition, KLF6-SV1 is a novel antiapoptotic protein in lung cancer cell lines, and targeted reduction of KLF6-SV1 using siRNA induces apoptosis both alone and in combination with the chemotherapeutic drug cisplatin. Together, these findings highlight a critical role for KLF6-SV1 in lung cancer, and show a potential novel therapeutic strategy for the treatment of lung cancer.
Primary management of melanoma
Authors: F.H.J. RAMPEN, A. KINT, J.A.A. HUNTER, H-J. HULSEBOSCH
Journal: British Journal of Dermatology (1984)

A questionnaire was sent to all consultant dermatologists in The Netherlands, Belgium and Scotland regarding their management of suspected melanomas. The 343 evaluable responses showed that 29·7% of the dermatologists regularly prefer to ‘wait and see’ or carry out incisional biopsies in the early management of suspected melanoma, especially if the risk is thought low. The main arguments advanced by the proponents of incision were doubts about whether incisional biopsy provokes metastatic spread, and the belief that a pathologist can make reliable diagnosis on a partial specimen of the tumour. These arguments are questioned and excision biopsy, provided it is feasible without being disfiguring, is strongly recommended in the initial treatment of a suspected melanoma.
A Note on Fat Embolism
Authors: H. J. Nightingale
Journal: BMJ (1945)

The speedy recognition and treatment of the obstructed airway and of the pneumoperitoneum undoubtedly saved the life of this moribund patient. Case IIA boy aged 54 was admitted to hospital for bronchography under general anaesthesia.Acute mediastinal emphysema and a bilateral shallow pneumothorax occurred as a result of a sudden delivery of oxygen into an intratracheal catheter, the accident being due to a faulty check-valve.Acute emphysema quickly developed, beginning with the eyelids and rapidly involving the face, neck, and upper chest.Needles were inserted into the neck, and the superior mediastinum was entered; no air could be aspirated.The left chest seemed hyperresonant, but no air escaped from a needle inserted into it.Oxygen was given by the B.L.B. mask, and the child made a complete and uneventful recovery.He was discharged five days after bronchography, the radiograph taken on discharge showing that both lungs had completely re-expanded.
Altered gene expression in myeloproliferative disorders correlates with activation of signaling by the V617F mutation of Jak2
Authors: Robert Kralovics, Soon-Siong Teo, Andreas S. Buser, Martin Brutsche, Ralph Tiedt, Andre Tichelli, Francesco Passamonti, Daniela Pietra, Mario Cazzola, Radek C. Skoda
Journal: Blood (2005)
Positive Selection on the Gene RNASEL: Correlation between Patterns of Evolution and Function
Authors: W. Jin, D.-D. Wu, X. Zhang, D. M. Irwin, Y.-P. Zhang
Journal: Molecular Biology and Evolution (2012)

RNASEL is a 2-5A-dependent endoribonuclease that is a component of the interferon-induced 2-5A system, which plays a crucial role in the antiviral and apoptotic activities of interferons. In humans, many polymorphic sites within the RNASEL gene have been associated with an increased risk of developing prostate cancer. Here, we obtained coding sequences for the RNASEL gene from 11 primates and found evidence that positive selection has operated on the C-terminal endoribonuclease domain and the N-terminal ankyrin repeats domain of the protein, domains that directly interact with virus (i.e., ankyrin repeats are responsible for receiving environmental signals, and the endoribonuclease catalyses the destruction of the pathogenic viral RNA). To extend this finding, we studied variation within this gene in modern human populations by resequencing alleles from 144 individuals representing four separate populations. Interestingly, the frequency of the 541D allele shows a negative association with the incidence rate of prostate cancer in worldwide populations, and haplotypes containing the 541D polymorphisms demonstrate signatures of positive selection. RNASEL variants having the 541D haplotype likely have a greater ability to defend against infections by viruses, thus the loss of this activity may be associated with the development of prostate cancer. We provide evidence that positive selection has operated on the RNASEL gene, and its evolution is correlated with its function in pathogen defense and cancer association.
Phenotype-Specific CpG Island Methylation Events in a Murine Model of Prostate Cancer
Authors: Marta Camoriano, Shannon R. Morey Kinney, Michael T. Moser, Barbara A. Foster, James L. Mohler, Donald L. Trump, Adam R. Karpf, Dominic J. Smiraglia
Journal: Cancer Research (2008)

Abstract Aberrant DNA methylation plays a significant role in nearly all human cancers and may contribute to disease progression to advanced phenotypes. Study of advanced prostate cancer phenotypes in the human disease is hampered by limited availability of tissues. We therefore took advantage of the Transgenic Adenocarcinoma of Mouse Prostate (TRAMP) model to study whether three different phenotypes of TRAMP tumors (PRIM, late-stage primary tumors; AIP, androgen-independent primary tumors; and MET, metastases) displayed specific patterns of CpG island hypermethylation using Restriction Landmark Genomic Scanning. Each tumor phenotype displayed numerous hypermethylation events, with the most homogeneous methylation pattern in AIP and the most heterogeneous pattern in MET. Several loci displayed a phenotype-specific methylation pattern; the most striking pattern being loci methylated at high frequency in PRIM and AIP but rarely in MET. Examination of the mRNA expression of three genes, BC058385, Goosecoid, and Neurexin 2, which exhibited nonpromoter methylation, revealed increased expression associated with downstream methylation. Only methylated samples showed mRNA expression, in which tumor phenotype was a key factor determining the level of expression. The CpG island in the human orthologue of BC058385 was methylated in human AIP but not in primary androgen-stimulated prostate cancer or benign prostate. The clinical data show a proof-of-principle that the TRAMP model can be used to identify targets of aberrant CpG island methylation relevant to human disease. In conclusion, phenotype-specific hypermethylation events were associated with the overexpression of different genes and may provide new markers of prostate tumorigenesis. [Cancer Res 2008;68(11):4173–82]
Modules, networks and systems medicine for understanding disease and aiding diagnosis
Authors: Mika Gustafsson, Colm E Nestor, Huan Zhang, Albert-László Barabási, Sergio Baranzini, Sören Brunak, Kian Fan Chung, Howard J Federoff, Anne-Claude Gavin, Richard R Meehan, Paola Picotti, Miguel Ángel Pujana, Nikolaus Rajewsky, Kenneth GC Smith, Peter J Sterk, Pablo Villoslada, Mikael Benson
Journal: Genome Medicine (2014)

Many common diseases, such as asthma, diabetes or obesity, involve altered interactions between thousands of genes. High-throughput techniques (omics) allow identification of such genes and their products, but functional understanding is a formidable challenge. Network-based analyses of omics data have identified modules of disease-associated genes that have been used to obtain both a systems level and a molecular understanding of disease mechanisms. For example, in allergy a module was used to find a novel candidate gene that was validated by functional and clinical studies. Such analyses play important roles in systems medicine. This is an emerging discipline that aims to gain a translational understanding of the complex mechanisms underlying common diseases. In this review, we will explain and provide examples of how network-based analyses of omics data, in combination with functional and clinical studies, are aiding our understanding of disease, as well as helping to prioritize diagnostic markers or therapeutic candidate genes. Such analyses involve significant problems and limitations, which will be discussed. We also highlight the steps needed for clinical implementation.
Predictions in the light of your own action repertoire as a general computational principle
Authors: Peter König, Niklas Wilming, Kai Kaspar, Saskia K. Nagel, Selim Onat
Journal: Behavioral and Brain Sciences (2013)

We argue that brains generate predictions only within the constraints of the action repertoire. This makes the computational complexity tractable and fosters a step-by-step parallel development of sensory and motor systems. Hence, it is more of a benefit than a literal constraint and may serve as a universal normative principle to understand sensorimotor coupling and interactions with the world.
An Illustrated Review of Early Pancreas Development in the Mouse
Authors: Mette Christine Jørgensen, Jonas Ahnfelt-Rønne, Jacob Hald, Ole D. Madsen, Palle Serup, Jacob Hecksher-Sørensen
Journal: Endocrine Reviews (2007)

Pancreas morphogenesis and cell differentiation are highly conserved among vertebrates during fetal development. The pancreas develops through simple budlike structures on the primitive gut tube to a highly branched organ containing many specialized cell types. This review presents an overview of key molecular components and important signaling sources illustrated by an extensive three-dimensional (3D) imaging of the developing mouse pancreas at single cell resolution. The 3D documentation covers the time window between embryonic days 8.5 and 14.5 in which all the pancreatic cell types become specified and therefore includes gene expression patterns of pancreatic endocrine hormones, exocrine gene products, and essential transcription factors. The 3D perspective provides valuable insight into how a complex organ like the pancreas is formed and a perception of ventral and dorsal pancreatic growth that is otherwise difficult to uncover. We further discuss how this global analysis of the developing pancreas confirms and extends previous studies, and we envisage that this type of analysis can be instrumental for evaluating mutant phenotypes in the future.
Stretch Enhances Contraction of Bovine Coronary Arteries via an NAD(P)H Oxidase–Mediated Activation of the Extracellular Signal–Regulated Kinase Mitogen-Activated Protein Kinase Cascade
Authors: Richard A. Oeckler, Pawel M. Kaminski, Michael S. Wolin
Journal: Circulation Research (2003)

This study examines the effects of an increase in passive stretch in endothelium-removed bovine coronary artery on oxidant-induced changes in force generation. Increasing passive stretch on the arterial segments from 5 to 20 g for 20 minutes caused a subsequent increase ( P &lt;0.05) in force generation to 30 mmol/L KCl or 0.1 μmol/L serotonin compared with the prestretch control response. Also associated with the passive stretch were increases in superoxide detection by lucigenin and a selective increase in extracellular signal–regulated kinase (ERK) mitogen-activated protein (MAP) kinase phosphorylation measured by Western analysis. The stretch-induced increase in force generation was eliminated by inhibition of the ERK pathway by the MEK inhibitor PD98059 but not by inhibitors of the p38 MAP kinase pathway (SB202190) or c-Jun N-terminal protein kinase pathway (SP200169). Additionally, stretch-induced increases in both ERK phosphorylation and force generation were attenuated by inhibition of tyrosine kinases (genistein), src (PP2), and specific sites on the epidermal growth factor receptor (EGFR) (AG1478). Probes for oxidant signaling, including NAD(P)H oxidase inhibitors (diphenyliodonium and apocynin) or enhancement of peroxide consumption (ebselen) but not inhibition of xanthine oxidase (allopurinol), attenuated the effects of stretch on both ERK phosphorylation and force generation. Furthermore, stretch caused an increase in EGFR phosphorylation and cytosolic to membrane translocation of the p47phox NAD(P)H oxidase subunit. Hydrogen peroxide also elicited contraction through EGFR phosphorylation and ERK. In summary, stretch seems to enhance force generation via ERK signaling through an EGFR/src-dependent mechanism activated by peroxide derived from a stretch-mediated activation of the NAD(P)H oxidase, a response that may contribute to hypertensive alterations in vascular reactivity.