tbuckley/cabot-search huggingface dataset:
A Nuclear DNA Phylogenetic Perspective on the Evolution of Echolocation and Historical Biogeography of Extant Bats (Chiroptera)
Authors: Geeta N. Eick, David S. Jacobs, Conrad A. Matthee
Journal: Molecular Biology and Evolution (2005)

Bats (Order Chiroptera), the only mammals capable of powered flight and sophisticated laryngeal echolocation, represent one of the most species-rich and ubiquitous orders of mammals. However, phylogenetic relationships within this group are poorly resolved. A robust evolutionary tree of Chiroptera is essential for evaluating the phylogeny of echolocation within Chiroptera, as well as for understanding their biogeographical history. We generated 4 kb of sequence data from portions of four novel nuclear intron markers for multiple representatives of 17 of the 18 recognized extant bat families, as well as the putative bat family Miniopteridae. Three echolocation-call characters were examined by mapping them onto the combined topology: (1) high-duty cycle versus low-duty cycle, (2) high-intensity versus low-intensity call emission, and (3) oral versus nasal emission. Echolocation seems to be highly convergent, and the mapping of echolocation-call design onto our phylogeny does not appear to resolve the question of whether echolocation had a single or two origins. Fossil taxa may also provide insight into the evolution of bats; we therefore evaluate 195 morphological characters in light of our nuclear DNA phylogeny. All but 24 of the morphological characters were found to be homoplasious when mapped onto the supermatrix topology, while the remaining characters provided insufficient information to reconstruct the placement of the fossil bat taxa with respect to extant families. However, a morphological synapomorphy characterizing the Rhinolophoidea was identified and is suggestive of a separate origin of echolocation in this clade. Dispersal-Vicariance analysis together with a relaxed Bayesian clock were used to evaluate possible biogeographic scenarios that could account for the current distribution pattern of extant bat families. Africa was reconstructed as the center of origin of modern-day bat families.
Sleep {middle dot} 4: Sleepiness, cognitive function, and quality of life in obstructive sleep apnoea/hypopnoea syndrome
Authors: H M Engleman
Journal: Thorax (2004)

Sleepiness, cognitive performance, and quality of life are overlapping aspects of daytime function that may be affected in patients with obstructive sleep apnoea/hypopnoea syndrome. The evidence is compatible with hypotheses that these deficits are reversible with treatment, particularly for patients with severe disease.
Quantitative T2 mapping of recurrent glioblastoma under bevacizumab improves monitoring for non-enhancing tumor progression and predicts overall survival
Authors: E. Hattingen, A. Jurcoane, K. Daneshvar, U. Pilatus, M. Mittelbronn, J. P. Steinbach, O. Bahr
Journal: Neuro-Oncology (2013)

Anti-angiogenic treatment in recurrent glioblastoma patients suppresses contrast enhancement and reduces vasogenic edema while non-enhancing tumor progression is common. Thus, the importance of T2-weighted imaging is increasing. We therefore quantified T2 relaxation times, which are the basis for the image contrast on T2-weighted images.Conventional and quantitative MRI procedures were performed on 18 patients with recurrent glioblastoma before treatment with bevacizumab and every 8 weeks thereafter until further tumor progression. We segmented the tumor on conventional MRI into 3 subvolumes: enhancing tumor, non-enhancing tumor, and edema. Using coregistered quantitative maps, we followed changes in T2 relaxation time in each subvolume. Moreover, we generated differential T2 maps by a voxelwise subtraction using the first T2 map under bevacizumab as reference.Visually segmented areas of tumor and edema did not differ in T2 relaxation times. Non-enhancing tumor volume did not decrease after commencement of bevacizumab treatment but strikingly increased at progression. Differential T2 maps clearly showed non-enhancing tumor progression in previously normal brain. T2 relaxation times decreased under bevacizumab without re-increasing at tumor progression. A decrease of <26 ms in the enhancing tumor following exposure to bevacizumab was associated with longer overall survival.Combining quantitative MRI and tumor segmentation improves monitoring of glioblastoma patients under bevacizumab. The degree of change in T2 relaxation time under bevacizumab may be an early response parameter predictive of overall survival. The sustained decrease in T2 relaxation times toward values of healthy tissue masks progressive tumor on conventional T2-weighted images. Therefore, quantitative T2 relaxation times may detect non-enhancing progression better than conventional T2-weighted imaging.
Increased Renal Responsiveness to Vasopressin and Enhanced V2 Receptor Signaling in RGS2 −/− Mice
Authors: Annie Mercier Zuber, Dustin Singer, Josef M. Penninger, Bernard C. Rossier, Dmitri Firsov
Journal: Journal of the American Society of Nephrology (2007)

The antidiuretic effect of vasopressin is mediated by V2 receptors (V2R) that are located in kidney connecting tubules and collecting ducts. This study provides evidence that V2R signaling is negatively regulated by regulator of G protein signaling 2 (RGS2), a member of the family of RGS proteins. This study demonstrates that (1) RGS2 expression in the kidney is restricted to the vasopressin-sensitive part of the nephron (thick ascending limb, connecting tubule, and collecting duct); (2) expression of RGS2 is rapidly upregulated by vasopressin; (3) the vasopressin-dependent accumulation of cAMP, the principal messenger of V2R signaling, is significantly higher in collecting ducts that are microdissected from the RGS2(-/-) mice compared with their wild-type littermates; and (4) analysis of urine output of mice that were exposed to water restriction followed by acute water loading revealed that RGS2(-/-) mice exhibit an increased renal responsiveness to vasopressin. It is proposed that RGS2 is involved in negative feedback regulation of V2R signaling.
Hedgehog/Notch-induced premature gliogenesis represents a new disease mechanism for Hirschsprung disease in mice and humans
Authors: Elly Sau-Wai Ngan, Maria-Mercè Garcia-Barceló, Benjamin Hon-Kei Yip, Hiu-Ching Poon, Sin-Ting Lau, Carmen Ka-Man Kwok, Eric Sat, Mai-Har Sham, Kenneth Kak-Yuen Wong, Brandon J. Wainwright, Stacey S. Cherny, Chi-Chung Hui, Pak Chung Sham, Vincent Chi-Hang Lui, Paul Kwong-Hang Tam
Journal: Journal of Clinical Investigation (2011)

Hirschsprung (HSCR) disease is a complex genetic disorder attributed to a failure of the enteric neural crest cells (ENCCs) to form ganglia in the hindgut. Hedgehog and Notch are implicated in mediating proliferation and differentiation of ENCCs. Nevertheless, how these signaling molecules may interact to mediate gut colonization by ENCCs and contribute to a primary etiology for HSCR are not known. Here, we report our pathway-based epistasis analysis of data generated by a genome-wide association study on HSCR disease, which indicates that specific genotype constellations of Patched (PTCH1) (which encodes a receptor for Hedgehog) and delta-like 3 (DLL3) (which encodes a receptor for Notch) SNPs confer higher risk to HSCR. Importantly, deletion of Ptch1 in mouse ENCCs induced robust Dll1 expression and activation of the Notch pathway, leading to premature gliogenesis and reduction of ENCC progenitors in mutant bowels. Dll1 integrated Hedgehog and Notch pathways to coordinate neuronal and glial cell differentiation during enteric nervous system development. In addition, Hedgehog-mediated gliogenesis was found to be highly conserved, such that Hedgehog was consistently able to promote gliogenesis of human neural crest-related precursors. Collectively, we defined PTCH1 and DLL3 as HSCR susceptibility genes and suggest that Hedgehog/Notch-induced premature gliogenesis may represent a new disease mechanism for HSCR.
Autonomic dysfunction in patients with nocturnal hypoventilation in extrapulmonary restrictive disease
Authors: J.P. Watson, J. Nolan, M.w Elliott
Journal: European Respiratory Journal (1999)

In chronic obstructive pulmonary disease, persistent hypoxia may be associated with autonomic dysfunction. The effect of nocturnal oxygen desaturation on autonomic function in patients with chest wall deformities and neuromuscular disease is unknown. This study examined the effect of nocturnal oxygen desaturation upon heart rate variability, a sensitive measure of autonomic function. Twenty-seven patients with chest wall deformity or neuromuscular disease underwent analysis of overnight oximetry, blood gases, and 24 h heart rate variability (HRV), specifically the standard deviation of normal-to-normal (SDNN) RR intervals, and the number of increases in successive NN intervals >50 ms (SNN50). Subjects were grouped according to nocturnal arterial oxygen saturation (Sa,O2): group 1 had episodes of Sa,O2 <90%, group 2 had Sa,O2 >90% throughout the night, and group 3 were 27 healthy age-matched controls who also underwent HRV analysis. The mean+/-SD SDNN for group 1 was 79.3+/-23.7 ms, less than group 2 (149.8+/-58.9 ms, p<0.02) and group 3 (155.1+/-37.1 ms, p<0.001). The geometric mean sNN50 was less in group 1 than group 2 (1,530 versus 5,843, p<0.01), but not significantly different from group 3 (2,712, p=0.053). There was no significant difference between groups 2 and 3. Within group 1, both SDNN and sNN50 were significantly lower in those patients with more severe nocturnal hypoxia. The minimum overnight Sa,O2 was the best predictor of abnormal HRV. In conclusion, patients with nocturnal hypoxia have evidence of autonomic dysfunction, even in cases with only transient episodes of nocturnal oxygen desaturation. The severity of autonomic dysfunction is related to the degree of nocturnal oxygen desaturation.
Trampoline training injuries--one hundred and ninety-five cases.
Authors: A. Hammer, A. L. Schwartzbach, P. E. Paulev
Journal: British Journal of Sports Medicine (1981)

In 198 people 201 trampoline injuries are analysed. All except three adults were re-examined, following an observation period of one to four years. School children (145) represented the major part of the 195 persons re-examined. Handling the large trampoline injured 21 of the 145 school children and six children at clubs. Injuries of a permanent nature were found in 49 of the 195 who were re-examined. The biomechanics and physiology of trampoline jumping is evaluated. Mismatch of a multitude of sensory impulses (visual, tactile, others) with impulses from the vestibular apparatus converging towards the orientation centres of the brain, may result in disorientation and then in the inadequate motor reactions actually seen at the time of the trampoline accidents. A G-induced split second loss of consciousness is another possible explanation of the trampoline accident. More secure procedures than trampolining as a school-sport and recreational activity are recommended.
Toll-like receptors mediate induction of hepcidin in mice infected with Borrelia burgdorferi
Authors: Curry L. Koening, Jennifer C. Miller, Jenifer M. Nelson, Diane M. Ward, James P. Kushner, Linda K. Bockenstedt, Janis J. Weis, Jerry Kaplan, Ivana De Domenico
Journal: Blood (2009)
Attempts to identify viruses in rheumatoid synovial cells.
Authors: M Norval, B P Marmion
Journal: Annals of the Rheumatic Diseases (1976)

Synovial fibroblast cell strains derived from the synovial membranes of 7 patients with rheumatoid arthritis were examined for the presence of viruses, in particular leucoviruses. Seven similar synovial strains derived from patients with other arthritic conditions were used as a control group. Evidence of the presence of a virus or a viral genome was looked for by several methods of induction followed by 3H-uridine labelling of the cultures. In addition, the culture supernatant, after induction and after the synovial strains had been co-cultivated with a variety of cell lines from several species, was assayed for the presence of viral RNA-dependent DNA polymerase activity. The DNA-polymerase activity of the synovial cells themselves was also determined. No evidence was found by any of these techniques to indicate the presence of virus or viral information within the synovial fibroblasts.
Postoperative Nomogram Predicting the 10-Year Probability of Prostate Cancer Recurrence After Radical Prostatectomy
Authors: Andrew J. Stephenson, Peter T. Scardino, James A. Eastham, Fernando J. Bianco, Zohar A. Dotan, Christopher J. DiBlasio, Alwyn Reuther, Eric A. Klein, Michael W. Kattan
Journal: Journal of Clinical Oncology (2005)

A postoperative nomogram for prostate cancer recurrence after radical prostatectomy (RP) has been independently validated as accurate and discriminating. We have updated the nomogram by extending the predictions to 10 years after RP and have enabled the nomogram predictions to be adjusted for the disease-free interval that a patient has maintained after RP.Cox regression analysis was used to model the clinical information for 1,881 patients who underwent RP for clinically-localized prostate cancer by two high-volume surgeons. The model was externally validated separately on two independent cohorts of 1,782 patients and 1,357 patients, respectively. Disease progression was defined as a rising prostate-specific antigen (PSA) level, clinical progression, radiotherapy more than 12 months postoperatively, or initiation of systemic therapy.The 10-year progression-free probability for the modeling set was 79% (95% CI, 75% to 82%). Significant variables in the multivariable model included PSA (P = .002), primary (P < .0001) and secondary Gleason grade (P = .0006), extracapsular extension (P < .0001), positive surgical margins (P = .028), seminal vesicle invasion (P < .0001), lymph node involvement (P = .030), treatment year (P = .008), and adjuvant radiotherapy (P = .046). The concordance index of the nomogram when applied to the independent validation sets was 0.81 and 0.79.We have developed and validated as a robust predictive model an enhanced postoperative nomogram for prostate cancer recurrence after RP. Unique to predictive models, the nomogram predictions can be adjusted for the disease-free interval that a patient has achieved after RP.
Inefficiencies and High-Value Improvements in U.S. Cervical Cancer Screening Practice
Authors: Jane J. Kim, Nicole G. Campos, Stephen Sy, Emily A. Burger, Jack Cuzick, Philip E. Castle, William C. Hunt, Alan Waxman, Cosette M. Wheeler
Journal: Annals of Internal Medicine (2015)

Studies suggest that cervical cancer screening practice in the United States is inefficient. The cost and health implications of nonadherence in the screening process compared with recommended guidelines are uncertain.To estimate the benefits, costs, and cost-effectiveness of current cervical cancer screening practice and assess the value of screening improvements.Model-based cost-effectiveness analysis.New Mexico HPV Pap Registry; medical literature.Cohort of women eligible for routine screening.Lifetime.Societal.Current cervical cancer screening practice; improved adherence to guidelines-based screening interval, triage testing, diagnostic referrals, and precancer treatment referrals.Reductions in lifetime cervical cancer risk, quality-adjusted life-years (QALYs), lifetime costs, incremental cost-effectiveness ratios, and incremental net monetary benefits (INMBs).Current screening practice was associated with lower health benefit and was not cost-effective relative to guidelines-based strategies. Improvements in the screening process were associated with higher QALYs and small changes in costs. Perfect adherence to screening every 3 years with cytologic testing and adherence to colposcopy/biopsy referrals were associated with the highest INMBs ($759 and $741, respectively, at a willingness-to-pay threshold of $100,000 per QALY gained); together, the INMB increased to $1645.Current screening practice was inefficient in 100% of simulations. The rank ordering of screening improvements according to INMBs was stable over a range of screening inputs and willingness-to-pay thresholds.The effect of human papillomavirus vaccination was not considered.The added health benefit of improving adherence to guidelines, especially the 3-year interval for cytologic screening and diagnostic follow-up, may justify additional investments in interventions to improve U.S. cervical cancer screening practice.U.S. National Cancer Institute.
Histological appearances of putative montelukast related Churg-Strauss syndrome
Authors: G P Currie, L McKinlay, K M Kerr
Journal: Thorax (2008)

Leukotriene receptor antagonists (LTRA) are widely used in the treatment of asthma. Over the years, case reports have suggested a possible link between their introduction and the development of Churg–Strauss syndrome. The case we describe highlights a strong temporal relationship between the initiation of montelukast and appearance of features suggestive of Churg–Strauss syndrome; our patient went on to have a lung biopsy which confirmed the diagnosis. We speculate that the slightly atypical histological features observed (airway involvement by necrotising granulomas) could indicate changes caused by LTRA induced disease per se.

LTRAs have emerged as useful oral therapeutic adjuncts in the management of persistent asthma.1 These drugs are usually well tolerated2 although some reports have suggested a link between LTRAs and the development of Churg–Strauss syndrome. Most (although not all) of these cases have occurred where concomitant prescription of an LTRA has allowed a reduction in corticosteroid dose or corticosteroid withdrawal, in turn indicating that latent Churg–Strauss …
Alterations of the soluble proteome of airway epithelial cells in COPD
Authors: Tina Heyder, Maxie Kohler, Reza Karimi, Bettina Levänen, Anders Eklund, Johan Grunewald, C. Magnus Sköld, Åsa Wheelock
Journal: European Respiratory Journal (2013)

The increasing incidence of COPD is primarily driven by the female population. Altered smoking habits cannot fully explain the increasing COPD burden among women, indicating that gender-specific mechanistic differences contribute to disease progression. Here we investigated alterations in the airway epithelial proteome due to early stage COPD, with focus on gender-related differences. The soluble proteome of airway epithelium obtained from subjects from the Karolinska COSMIC study (age- and sex matched COPD patients (GOLD I-II), smokers with normal lung function, and never-smoking healthy controls of both genders (n=20; 120 subjects total)) was analyzed by Difference Gel Electrophoresis (DIGE), followed by multivariate modeling. Comparison of non-symptomatic smokers and smoking COPD patients showed significant differences between groups for both genders (Male: R2= 0.98, Q2=0.95, p=0.0007; Female: R2= 0.82, Q2=0.73, p=0.01). Only 3 of the 22 proteins driving the separation between male healthy smokers and smoking COPD patients were the same as for the corresponding female population, indicating significant gender differences. This pilot study indicates mechanistic gender differences in the airway epithelial proteome distinct from our recent report regarding alveolar macrophages (1). New insight into gender-specific disease mechanisms and a better molecular understanding of the various sub-phenotypes of COPD are necessary to hamper the increasing morbidity of the disease.  1. Kohler M, Sandberg A, et al (2012). J Allergy Clin Immunol. In press.
Evolving Treatment of Advanced Colon Cancer
Authors: Neil H. Segal, Leonard B. Saltz
Journal: Annual Review of Medicine (2009)

Colorectal cancer is a common malignancy worldwide. Despite significant developments in the treatment of this disease, it still causes considerable morbidity and mortality. Recent advances include both newer cytotoxic chemotherapies and novel biologic agents. Although overall progress has been more modest than had been hoped, substantial benefits have been achieved for some patients, and the number of treatment options has substantially increased. Perhaps most importantly, treatment regimens can now be selected and tailored toward the individual patient following an informed discussion between the patient and the treating oncologist. We present in detail these recent advances and provide some insight into several promising future strategies.
Analysis of KIT Mutations in Sporadic and Familial Gastrointestinal Stromal Tumors: Therapeutic Implications through Protein Modeling
Authors: Chi Tarn, Erin Merkel, Adrian A. Canutescu, Wei Shen, Yuliya Skorobogatko, Martin J. Heslin, Burton Eisenberg, Ruth Birbe, Arthur Patchefsky, Roland Dunbrack, J. Pablo Arnoletti, Margaret von Mehren, Andrew K. Godwin
Journal: Clinical Cancer Research (2005)

Abstract Purpose: Gastrointestinal stromal tumors (GIST) are characterized by expressing a gain-of-function mutation in KIT, and to a lesser extent, PDGFR. Imatinib mesylate, a tyrosine kinase inhibitor, has activity against GISTs that contain oncogenic mutations of KIT. In this study, KIT and PDGFRα mutation status was analyzed and protein modeling approaches were used to assess the potential effect of KIT mutations in response to imatinib therapy. Experimental Design: Genomic DNA was isolated from GIST tumors. Exons 9, 11, 13, and 17 of c-KIT and exons 12, 14, and 18 of PDGFRα were evaluated for oncogenic mutations. Protein modeling was used to assess mutations within the juxtamembrane region and the kinase domain of KIT. Results: Mutations in KIT exons 9, 11, and 13 were identified in GISTs with the majority of changes involving the juxtamembrane region of KIT. Molecular modeling indicates that mutations in this region result in disruption of the KIT autoinhibited conformation, and lead to gain-of-function activation of the kinase. Furthermore, a novel germ-line mutation in KIT was identified that is associated with an autosomal dominant predisposition to the development of GIST. Conclusions: We have used protein modeling and structural analyses to elucidate why patients with GIST tumors containing exon 11 mutations are the most responsive to imatinib mesylate treatment. Importantly, mutations detected in this exon and others displayed constitutive activation of KIT. Furthermore, we have found tumors that are both KIT and PDGFRα mutation negative, suggesting that additional, yet unidentified, abnormalities may contribute to GIST tumorigenesis.
Case Number 26: Massive cholesterol crystal deposition: unusual location in rheumatoid arthritis
Authors: P V Balint
Journal: Annals of the Rheumatic Diseases (2003)

A 71 year old white man with seropositive erosive rheumatoid arthritis (RA) for 28 years presented with swelling of the left ankle that had been increasing in size for three years and was now interfering with shoe fitting. On examination a 2.5 cm diameter non-inflamed, well circumscribed, firm mass—initially presumed to be a rheumatoid nodule or tense synovial cyst—was noted on the anteromedial aspect …