tbuckley/cabot-search huggingface dataset:
Cell-specific Gene Expression in Patients with Usual Interstitial Pneumonia
Authors: Margaret M. Kelly, Richard Leigh, Sarah E. Gilpin, Elaine Cheng, Gail E. M. Martin, Katherine Radford, Gerard Cox, Jack Gauldie
Journal: American Journal of Respiratory and Critical Care Medicine (2006)

Usual interstitial pneumonia (UIP) is characterized by extracellular matrix deposition and the development of pulmonary fibrosis. Fibroblastic foci found in the lung are believed to represent an early stage in the evolution of this disease.To compare gene expression profiles in different components of lung tissue (fibroblastic foci, adjacent epithelium, and areas of type 2 pneumocyte hyperplasia) from patients with UIP, and contrast these profiles to distal, uninvolved (control) alveolar tissue from patients undergoing lung resection for cancer.Lung resection tissue (UIP, n = 11; controls, n = 11) was snap-frozen for subsequent laser capture microdissection, followed by mRNA extraction, linear amplification, and quantitative real-time polymerase chain reaction.In patients with UIP, tissue inhibitor of matrix metalloprotease-1 and matrix metalloprotease (MMP)-2 gene expression was up-regulated within the fibroblastic foci compared with the overlying epithelium (p = 0.03, p = 0.02), and to control alveoli (p = 0.001, p = 0.04), respectively. MMP-9 and MMP-7, as well as osteopontin, were up-regulated in fibroblastic foci (p = 0.01, p = 0.08, p = 0.08), the adjacent epithelium (p = 0.001, p = 0.001, p = 0.03), and the hyperplastic type 2 pneumocytes (p = 0.02, p = 0.001, p = 0.08), respectively, compared with control alveoli.Altered gene expression of important profibrotic mediators in the different cellular lung compartments in patients with UIP likely plays an important role in pathogenesis of the deranged extracellular matrix deposition and subsequent fibrosis in this condition.
Dimensions of Religiosity and Their Relationship to Lifetime Psychiatric and Substance Use Disorders
Authors: Kenneth S. Kendler, Xiao-Qing Liu, Charles O. Gardner, Michael E. McCullough, David Larson, Carol A. Prescott
Journal: American Journal of Psychiatry (2003)

The role of religion in mental illness remains understudied. Most prior investigations of this relationship have used measures of religiosity that do not reflect its complexity and/or have examined a small number of psychiatric outcomes. This study used data from a general population sample to clarify the dimensions of religiosity and the relationships of these dimensions to risk for lifetime psychiatric and substance use disorders.Responses to 78 items assessing various aspects of broadly defined religiosity were obtained from 2,616 male and female twins from a general population registry. The association between the resulting religiosity dimensions and the lifetime risk for nine disorders assessed at personal interview was evaluated by logistic regression. Of these disorders, five were "internalizing" (major depression, phobias, generalized anxiety disorder, panic disorder, and bulimia nervosa), and four were "externalizing" (nicotine dependence, alcohol dependence, drug abuse or dependence, and adult antisocial behavior).Seven factors were identified: general religiosity, social religiosity, involved God, forgiveness, God as judge, unvengefulness, and thankfulness. Two factors were associated with reduced risk for both internalizing and externalizing disorders (social religiosity and thankfulness), four factors with reduced risk for externalizing disorders only (general religiosity, involved God, forgiveness, and God as judge), and one factor with reduced risk for internalizing disorders only (unvengefulness).Religiosity is a complex, multidimensional construct with substantial associations with lifetime psychopathology. Some dimensions of religiosity are related to reduced risk specifically for internalizing disorders, and others to reduced risk specifically for externalizing disorders, while still others are less specific in their associations. These results do not address the nature of the causal link between religiosity and risk for illness.
Protective efficacy of oral whole-cell/recombinant-B-subunit cholera vaccine in Peruvian military recruits
Authors: J.L Sanchez, B Vasquez, R.E Begue, R Meza, G Castellares, C Cabezas, D.M Watts, A-M Svennerholm, J.C Sadoff, D.N Taylor
Journal: The Lancet (1994)
DiagHunter and GenoPix2D: programs for genomic comparisons, large-scale homology discovery and visualization
Authors: Steven B Cannon, Alexander Kozik, Brian Chan, Richard Michelmore, Nevin D Young
Journal: Genome biology (2003)

The DiagHunter and GenoPix2D applications work together to enable genomic comparisons and exploration at both genome-wide and single-gene scales. DiagHunter identifies homologous regions (synteny blocks) within or between genomes. DiagHunter works efficiently with diverse, large datasets to predict extended and interrupted synteny blocks and to generate graphical and text output quickly. GenoPix2D allows interactive display of synteny blocks and other genomic features, as well as querying by annotation and by sequence similarity.
Real-Time Gap Ligase Chain Reaction
Authors: Susan V. Harden, David C. Thomas, Nicole Benoit, Khalid Minhas, William H. Westra, Joseph A. Califano, Wayne Koch, David Sidransky
Journal: Clinical Cancer Research (2004)

Abstract Purpose: We have developed a real-time semiquantitative gap ligase chain reaction for detecting p53 point mutations at low level in a background of excess of wild-type DNA. Experimental Design: This method was validated by direct comparison to a previously validated but cumbersome phage plaque hybridization assay. Forty-one surgical margins and lymph nodes from 10 cases of head and neck squamous cell carcinoma and lung carcinoma were tested for p53 mutant clones. Results: Both methods detected p53 mutants in margins from 8 of the 10 cases, whereas standard pathology detected cancer cells in only 3 cases. Positive margins included tissue samples with a tumor/normal DNA ratio of up to 1:1000. Conclusions: This novel molecular approach can be performed in &amp;lt;5 h facilitating intraoperative use for real-time surgical resection.
Role of microRNAs in the reperfused myocardium towards post-infarct remodelling
Authors: H. Zhu, G.-C. Fan
Journal: Cardiovascular Research (2011)

Myocardial ischaemia/reperfusion (I/R)-induced remodelling generally includes cell death (necrosis and apoptosis), myocyte hypertrophy, angiogenesis, cardiac fibrosis, and myocardial dysfunction. It is becoming increasingly clear that microRNAs (miRNAs or miRs), a group of highly conserved small (∼18–24 nucleotide) non-coding RNAs, fulfil specific functions in the reperfused myocardium towards post-infarct remodelling. While miR-21, -133, -150, -195, and -214 regulate cardiomyocyte hypertrophy, miR-1/-133 and miR-208 have been elucidated to influence myocardial contractile function. In addition, miR-21, -24, -133, -210, -494, and -499 appear to protect myocytes against I/R-induced apoptosis, whereas miR-1, -29, -199a, and -320 promote apoptosis. Myocardial fibrosis can be regulated by the miR-29 family and miR-21. Moreover, miR-126 and miR-210 augment I/R-induced angiogenesis, but miR-24, -92a, and -320 suppress post-infarct neoangiogenesis. In this review, we summarize the latest advances in the identification of myocardial ischaemia-associated miRNAs and their functional significance in the modulation of I/R-triggered remodelling. Controversial effects of some miRNAs in post-infarct remodelling will be also discussed.
Clinical characteristics and survival in patients with idiopathic pulmonary fibrosis with and without associated emphysema
Authors: Malgorzata Sobiecka, Karina Onish, Piotr Boros, Stefan Wesolowski, Jan Kus
Journal: European Respiratory Journal (2013)

It has been suggested that the presence of emphysema alters physiology and survival in patients with idiopathic pulmonary fibrosis (IPF).  A cohort of 56 IPF patients was evaluated (32 men; mean age 62±10 yrs; 31 smokers). High-resolution CT scans were examined by experienced radiologist blinded to clinical data. The amount of emphysema (numerical score) were assessed in each patient, and cases were placed into one of three groups: no emphysema - emphysema score of zero (ES=0), mild emphysema (0 2). Clinical characteristics, smoking history, pulmonary function test (PFT) and patients survival were analysed.  Results: There were 31 IPF patients without emphysema, 11 with mild and 14 with advanced emphysema. Studied groups did not differ significantly with regard to smoking history, right ventricular systolic pressure (RVSP), PFT and 6-minute walk test findings. Patients with IPF associated with mild and advanced emphysema more frequently were men compared to patients with IPF without emphysema (82% and 71% vs 42%, respectively, p=0,03). Median follow-up [1st, 3rd quartiles] was 30 [14, 52] months and 16 patients died in this period (3 due to lung cancer, 12 due to IPF). Patients who died had lower mean VC (76 vs 89% pred., p=0.02), TLC (72 vs 81% pred., p=0,04), DLCO (36 vs 48% pred., p=0.005) and higher RVSP (51 vs 41 mmHg, p=0.03). Median survival of IPF patients with mild and advanced emphysema did not differ significantly compared to IPF patients without emphysematous changes (26, 31 and 30 months, respectively; p=0,14).  Conclusion: Emphysema associated with IPF does not affect the mortality rate compared to IPF alone.
The Previously Undescribed ZKSCAN3 (ZNF306) Is a Novel “Driver” of Colorectal Cancer Progression
Authors: Lin Yang, Stanley R. Hamilton, Anil Sood, Toshio Kuwai, Lee Ellis, Angela Sanguino, Gabriel Lopez-Berestein, Douglas D. Boyd
Journal: Cancer Research (2008)

A relatively new view of colorectal cancer is that its development/progression reflects the contribution of a large set of altered gene products in varying combinations, each providing a "fitness advantage." In searching for novel contributing gene products using Unigene cluster data mining, we found overrepresentation of expressed sequence tags corresponding to a previously uncharacterized gene (ZKSCAN3) in colorectal tumors. ZKSCAN3 was pursued for several reasons: (a) its sequence similarity with bowl required for Drosophila hindgut development; (b) it lies in a chromosomal region (6p22.1) amplified in colorectal cancer; and (c) its coding sequence predicts tandem C(2)H(2) zinc finger domains present in a class of proteins gaining attention for their role in oncogenesis/tumor progression. Reverse transcription-PCR confirmed overexpression in colorectal tumor tissue compared with adjacent nonmalignant mucosa due in part to gene amplification determined by Southern blotting. Further, immunohistochemistry with an antibody generated to the predicted protein sequence revealed higher ZKSCAN3 expression in invasive compared with noninvasive tumors. Intriguingly, the ZKSCAN3 protein was also expressed in tumors wild-type for genes (APC, p53, K-Ras) commonly targeted in colorectal cancer. ZKSCAN3 knockdown in two independent colon cancer cell lines impaired anchorage-independent growth and orthotopic tumor growth, whereas overexpression in a third cell line had the opposite effect and increased 5-fluorouracil resistance. Liposomal delivery of a ZKSCAN3-targeting small interfering RNA reduced tumorigenicity of orthotopic colon cancer. Thus, the hitherto uncharacterized ZKSCAN3 adds to an expanding set of encoded products contributing to the progression of colorectal cancer.
Simulations of Enhancer Evolution Provide Mechanistic Insights into Gene Regulation
Authors: Thyago Duque, Md. Abul Hassan Samee, Majid Kazemian, Hannah N. Pham, Michael H. Brodsky, Saurabh Sinha
Journal: Molecular Biology and Evolution (2013)

There is growing interest in models of regulatory sequence evolution. However, existing models specifically designed for regulatory sequences consider the independent evolution of individual transcription factor (TF)–binding sites, ignoring that the function and evolution of a binding site depends on its context, typically the cis-regulatory module (CRM) in which the site is located. Moreover, existing models do not account for the gene-specific roles of TF-binding sites, primarily because their roles often are not well understood. We introduce two models of regulatory sequence evolution that address some of the shortcomings of existing models and implement simulation frameworks based on them. One model simulates the evolution of an individual binding site in the context of a CRM, while the other evolves an entire CRM. Both models use a state-of-the art sequence-to-expression model to predict the effects of mutations on the regulatory output of the CRM and determine the strength of selection. We use the new framework to simulate the evolution of TF-binding sites in 37 well-studied CRMs belonging to the anterior–posterior patterning system in Drosophila embryos. We show that these simulations provide accurate fits to evolutionary data from 12 Drosophila genomes, which includes statistics of binding site conservation on relatively short evolutionary scales and site loss across larger divergence times. The new framework allows us, for the first time, to test hypotheses regarding the underlying cis-regulatory code by directly comparing the evolutionary implications of the hypothesis with the observed evolutionary dynamics of binding sites. Using this capability, we find that explicitly modeling self-cooperative DNA binding by the TF Caudal (CAD) provides significantly better fits than an otherwise identical evolutionary simulation that lacks this mechanistic aspect. This hypothesis is further supported by a statistical analysis of the distribution of intersite spacing between adjacent CAD sites. Experimental tests confirm direct homodimeric interaction between CAD molecules as well as self-cooperative DNA binding by CAD. We note that computational modeling of the D. melanogaster CRMs alone did not yield significant evidence to support CAD self-cooperativity. We thus demonstrate how specific mechanistic details encoded in CRMs can be revealed by modeling their evolution and fitting such models to multispecies data.
Unusual Cause of Nerve Entrapment
Authors: Clifford Fraim, Bruce H. Peters
Journal: JAMA (1979)

<h3>To the Editor.—</h3> Peripheral nerve entrapment syndromes are common and may cause pain and dysfunction in a normal-appearing limb. These may arise from unusual activities, as in the following case. <h3>Report of a Case.—</h3> A 35-year-old woman had been well until, for the first time, she engaged in several hours of vigorous Frisbee-throwing. Transient mild pain in the right shoulder and elbow was followed in five days by inability to extend the right wrist or fingers. Palpation anterior to the right lateral epicondyle produced pain, and there was weakness of the right wrist (20% of normal) and finger (40% of normal) extensors as well as supinator weakness (50% of normal). Other muscle function was normal, as were sensation, reflexes, and roentgenograms of the right arm. Her strength slowly returned to normal. <h3>Comment.—</h3> This This case is an example of posterior interosseus nerve entrapment due to "Frisbee-flinging." The pathophysiologic mechanism is
Clinical and temporal characteristics of chronic bronchitis complicated with secondary bronchiectasis
Authors: Mykola Ostrovskyy, Tetiana Bondarenko, Oleksandr Varunkiv, Mariana Kulynych-Miskiv, Galyna Korzh, Mykola Stovban
Journal: European Respiratory Journal (2013)

Backgraund. According to the epidemiological researches prevalence of a chronic bronchitis (CB) varies in the broad borders on average from 10 to 47 % in the different countries of the world.  Purpose of the study was to study the clinic pathogenic peculiarities of CB exacerbation, namely the inflammatory condition and the frequency of complication appearing, such as secondary bronchiectasis.  Materials and methods. We observed the type of exacerbation and the presence of CB complications with secondary bronchiectasis in 140 patients during the year which were divided into two groups. I group – 80 patients who were diagnosed with CB for 10 years and II group – 60 patients were sick with CB for 20 years. The type of exacerbation (catarrhal or purulent) and the presence of chronic bronchitis complicated with secondary bronchiectasis (according to the data of fiber-optic bronchoscopy and computer tomography) were estimated in the patients during the year.  Results of the study. In the 1st group during the year the 80% of patients had catarrhal exacerbation, and 20% had purulent one. Only 5% patients of this group had CB complicated with secondary bronchiectasis.  In the 2nd group (anamnesis chronic bronchitis for 20 years) during the year the 40% of patients had catarrhal exacerbation, and 60% had purulent one. Already 11,7% patients of this group had CB complicated with secondary bronchiectasis.  Conclusions. As well as the time of sickness of CB lengthens, increases the frequency of purulent complications and the identification of the secondary bronchiectasis increases in three times.
Multipotent Vasculogenic Pericytes From Human Pluripotent Stem Cells Promote Recovery of Murine Ischemic Limb
Authors: Ayelet Dar, Hagit Domev, Oren Ben-Yosef, Maty Tzukerman, Naama Zeevi-Levin, Atara Novak, Igal Germanguz, Michal Amit, Joseph Itskovitz-Eldor
Journal: Circulation (2011)

Pericytes represent a unique subtype of microvessel-residing perivascular cells with diverse angiogenic functions and multilineage developmental features of mesenchymal stem cells. Although various protocols for derivation of endothelial and/or smooth muscle cells from human pluripotent stem cells (hPSC, either embryonic or induced) have been described, the emergence of pericytes in the course of hPSC maturation has not yet been elucidated.We found that during hPSC development, spontaneously differentiating embryoid bodies give rise to CD105(+)CD90(+)CD73(+)CD31(-) multipotent clonogenic mesodermal precursors, which can be isolated and efficiently expanded. Isolated and propagated cells expressed characteristic pericytic markers, including CD146, NG2, and platelet-derived growth factor receptor β, but not the smooth muscle cell marker α-smooth muscle actin. Coimplantation of hPSC-derived endothelial cells with pericytes resulted in functional and rapid anastomosis to the murine vasculature. Administration of pericytes into immunodeficient mice with limb ischemia promoted significant vascular and muscle regeneration. At day 21 after transplantation, recruited hPSC pericytes were found incorporated into recovered muscle and vasculature.Derivation of vasculogenic and multipotent pericytes from hPSC can be used for the development of vasculogenic models using multiple vasculogenic cell types for basic research and drug screening and can contribute to angiogenic regenerative medicine.
Measurement of Residual Breast Cancer Burden to Predict Survival After Neoadjuvant Chemotherapy
Authors: W. Fraser Symmans, Florentia Peintinger, Christos Hatzis, Radhika Rajan, Henry Kuerer, Vicente Valero, Lina Assad, Anna Poniecka, Bryan Hennessy, Marjorie Green, Aman U. Buzdar, S. Eva Singletary, Gabriel N. Hortobagyi, Lajos Pusztai
Journal: Journal of Clinical Oncology (2007)

To measure residual disease after neoadjuvant chemotherapy in order to improve the prognostic information that can be obtained from evaluating pathologic response.Pathologic slides and reports were reviewed from 382 patients in two different treatment cohorts: sequential paclitaxel (T) then fluorouracil, doxorubicin, and cyclophosphamide (FAC) in 241 patients; and a single regimen of FAC in 141 patients. Residual cancer burden (RCB) was calculated as a continuous index combining pathologic measurements of primary tumor (size and cellularity) and nodal metastases (number and size) for prediction of distant relapse-free survival (DRFS) in multivariate Cox regression analyses.RCB was independently prognostic in a multivariate model that included age, pretreatment clinical stage, hormone receptor status, hormone therapy, and pathologic response (pathologic complete response [pCR] v residual disease [RD]; hazard ratio = 2.50; 95% CI 1.70 to 3.69; P < .001). Minimal RD (RCB-I) in 17% of patients carried the same prognosis as pCR (RCB-0). Extensive RD (RCB-III) in 13% of patients was associated with poor prognosis, regardless of hormone receptor status, adjuvant hormone therapy, or pathologic American Joint Committee on Cancer stage of residual disease. The generalizability of RCB for prognosis of distant relapse was confirmed in the FAC-treated validation cohort.RCB determined from routine pathologic materials represented the distribution of RD, was a significant predictor of DRFS, and can be used to define categories of near-complete response and chemotherapy resistance.
Distribution Theory of Resistance of Neurogenic Vasoconstriction to Alpha-Receptor Blockade in the Rabbit
Authors: JOHN A. BEVAN, CHE SU
Journal: Circulation Research (1971)

The effects of α-receptor-blocking agents on the contractile responses of isolated rabbit arteries to sympathetic nerve stimulation and exogenous l -norepinephrine ( l -NE) were compared. In the pulmonary artery and aorta, yohimbine, phentolamine, and phenoxybenzamine blocked the response to nerve stimulation less than that to an equipotent dose of l -NE. This resistance of neurogenic response was independent of the frequency and number of stimuli and persisted after inhibition of the nerve l -NE uptake by cocaine. The neurogenically released transmitter l -NE probably forms a high concentration near the adventitia-media junction, whereas the exogenous NE is distributed evenly throughout the thickness of media. Thus higher concentrations of α-receptor-blocking agents would be needed to block the effect of neurogenic l -NE than to block that of exogenous l -NE. This explanation of the resistance was thought to be more appropriate to the large vessels tested than that based on neuroeffector proximity.
Somatic Taeniasis and Cysticercosis Epilepsy
Authors: T. V. Pearce
Journal: BMJ (1941)

<h3>Objective</h3> Fear, anxiety, depression, distress and catastrophisation are all factors known to affect pain and disability levels. To date, the association of such psychological factors has yet to be established in tendinopathy. Therefore, the purpose of this paper was to determine if psychological variables are associated with tendinopathy and whether any such variables may be associated with pain and disability outcomes in conservative management of tendinopathy. <h3>Design</h3> A systematic review was undertaken and included studies were appraised for risk of bias using the Newcastle-Ottawa Scale. Owing to heterogeneity of studies, a qualitative synthesis was undertaken. <h3>Data sources</h3> An electronic search of MEDLINE, CiNAHL, SPORTDiscus, PsycINFO, EMBASE and PsycARTICLES was undertaken from their inception to April 2016. <h3>Eligibility criteria for selecting studies</h3> Any study design that incorporated psychological measures and clinical outcomes using participants with tendinopathy. <h3>Results</h3> Ten articles describing nine studies and 1108 participants were included. Conflicting evidence exists regarding the association of anxiety, depression and lateral epicondylalgia (LE). Strong evidence suggests LE is not associated with kinesiophobia. Moderate evidence links catastrophisation and distress with LE. Moderate evidence suggests distress is not associated with rotator cuff tendinopathy, but kinesiophobia and catastrophisation are. Limited evidence suggests patellar tendinopathy is not associated with anxiety or depression and kinesiophobia may be linked with suboptimal outcomes in Achilles tendinopathy. <h3>Summary/conclusions</h3> Tendinopathy requires an individualised approach to management. Clinicians should consider using validated screening tools for the presence of psychological variables as a part of their holistic management.