tbuckley/cabot-search huggingface dataset:
Trajectories of Lung Function during Childhood
Authors: Danielle C. M. Belgrave, Iain Buchan, Christopher Bishop, Lesley Lowe, Angela Simpson, Adnan Custovic
Journal: American Journal of Respiratory and Critical Care Medicine (2014)

Developmental patterns of lung function during childhood may have major implications for our understanding of the pathogenesis of respiratory disease throughout life.To explore longitudinal trajectories of lung function during childhood and factors associated with lung function decline.In a population-based birth cohort, specific airway resistance (sRaw) was assessed at age 3 (n = 560), 5 (n = 829), 8 (n = 786), and 11 years (n = 644). Based on prospective data (questionnaires, skin tests, IgE), children were assigned to wheeze phenotypes (no wheezing, transient, late-onset, and persistent) and atopy phenotypes (no atopy, dust mite, non-dust mite, multiple early, and multiple late). We used longitudinal linear mixed models to determine predictors of change in sRaw over time.Contrary to the assumption that sRaw is independent of age and sex, boys had higher sRaw than girls (mean difference, 0.080; 95% confidence interval [CI], 0.049-0.111; P < 0.001) and a higher rate of increase over time. For girls, sRaw increased by 0.017 kPa ⋅ s(-1) per year (95% CI, 0.011-0.023). In boys this increase was significantly greater (P = 0.012; mean between-sex difference, 0.011 kPa ⋅ s(-1); 95% CI, 0.003-0.019). Children with persistent wheeze (but not other wheeze phenotypes) had a significantly greater rate of deterioration in sRaw over time compared with never wheezers (P = 0.009). Similarly, children with multiple early, but not other atopy phenotypes had significantly poorer lung function than those without atopy (mean difference, 0.116 kPa ⋅ s(-1); 95% CI, 0.065-0.168; P < 0.001). sRaw increased progressively with the increasing number of asthma exacerbations.Children with persistent wheeze, frequent asthma exacerbations, and multiple early atopy have diminished lung function throughout childhood, and are at risk of a progressive loss of lung function from age 3 to 11 years. These effects are more marked in boys.
1116-25 Percutaneous edge-to-edge repair for mitral regurgitation guided by transesophageal and transthoracic echocardiography
Authors: L Leonardo Rodriguez, Harry Acquatella, Susan Wiegers, Frank Silvestry, Alan Zunamon, John Merlino, Randy Martin, Kimberly Krabil, Elyse Foster, Ted Feldman, Jan Komtebedde, William J Stewart
Journal: Journal of the American College of Cardiology (2004)
Hospital Utilization among Chronic Dialysis Patients
Authors: PRADEEP ARORA, ANNAMARIA T. KAUSZ, GREGORIO T. OBRADOR, ROBIN RUTHAZER, SAMINA KHAN, CONSTANCE S. JENULESON, KLEMENS B. MEYER, BRIAN J. G. PEREIRA
Journal: Journal of the American Society of Nephrology (2000)

Abstract. Factors driving inpatient and outpatient utilization were studied among patients who began dialysis for chronic renal failure at the New England Medical Center (NEMC) between 1992 and 1997. Clinical, laboratory, and hospital resource utilization data were obtained from patient records and electronic databases. There were 2.2 hospitalizations and 14.8 hospital days per patient year at risk (PYAR). The number of hospitalizations and hospital days per PYAR were higher in the first 3 mo of initiating dialysis (4.3 and 28.3, respectively) compared to after 3 mo (1.9 and 12.9, respectively). Factors associated with increased risk of hospital days within the first 3 mo included non-health maintenance organization insurance, ischemic heart disease, late referral to the nephrologist, and use of temporary vascular access for the first dialysis. Patients with ischemic heart disease and who received dialysis during the years 1992-1994 compared with 1996-1997 had an increased risk of hospital days after 3 mo of initiating dialysis. There were 16.6 outpatient visits per PYAR, with significant differences in utilization between the first 3 mo and after 3 mo of initiating dialysis. Thus, hospital utilization was significantly higher in the first 3 mo compared to after 3 mo, and factors associated with hospital utilization depended on duration of dialysis. In particular, delayed referral to the nephrologist and lack of permanent vascular access were independently associated with increased risk of hospital utilization in the first 3 mo of dialysis. Greater attention to timely referral to the nephrologist and timely placement of vascular access could result in reduced utilization and cost savings.
Lipodystrophy and serum lipid abnormalities in HIV-positive sub-Saharan population on ART
Authors: Pietro Filippini, Carlo Scolastico, Martina Battaglia, Cesare Nacca, Nicola Coppola, Giovanni Rossi, Raffaella Pisapia, Salvatore Martini, Michele Imparato, Caterina Sagnelli, Felice Piccinino, Evangelista Sagnelli
Journal: Journal of Infection (2005)
QUANTIFICATION OF PRONEURAL GENE-EXPRESSION SIGNATURE OF GLIOMAS AND GLIOBLASTOMA-DERIVED SPHERES
Authors: K. Yoshimoto, H. Murata, R. Hatae, Y. Akagi, M. Mizoguchi, K. Iihara
Journal: Neuro-Oncology (2014)

BACKGROUND: High-throughput gene expression studies on glioblastoma have identified proneural (PN) gene-expression type as the one characterized by a strong expression of neurogenesis-related genes. Although the PN type is generally associated with good prognosis, the clinical and biological significance of the PN type has not been completely elucidated. In the current study, we aimed to expound the biological significance of the PN subtype by quantifying its gene signature in glioblastoma, low-grade gliomas, and glioblastoma-derived cellular spheres. METHODS: To evaluate the PN gene-expression signature of all the glioma grades, we quantified the expression signature of 82 gliomas (grade II, 14 gliomas; III, 16; and IV, 52) by using real-time reverse transcription PCR. All samples had been assessed for IDH mutation and 1p/19q co-deletion. We characterized the PN signature by estimating the relative expression score of nine PN markers (DLL3, BCAN, OLIG2, NKX2.2, ASCL1, SOX2, ERBB3, NCAM1, and NCAM2) and eight mesenchymal (MES) markers (YKL-40, CD44, Vimentin, COL1A1, TRL2, TRL4, TRADD, and RELB). In addition, we evaluated the expression signature of five matched glioblastoma tissues and glioblastoma-derived cellular spheres. RESULTS: The PN gene-expression signature was higher in low-grade gliomas than that in glioblastoma. In the IDH-wild glioblastoma (n = 42), 19% of the tumor was characteristic of the PN type, while 32% was of the MES type. The overall survival time was not significantly different between two types. The analysis of five glioblastoma-derived spheres demonstrated that two of them showed the PN signature, and the remaining three showed the MES signature. Glioblastoma-derived spheres showed a different expression signature from that of the originating tumor. In particular, two spheres derived from the MES glioblastoma showed the PN signature after successful expansion as neurospheres, suggesting a conversion of the MES to PN type under proliferating conditions. CONCLUSIONS: The expression analysis of glioma tissues showed that the PN signature is displayed early in gliomagenesis, and is not specific to a subset of glioblastomas. Given that the MES to PN conversion is a frequent event under proliferating conditions, a display of the subtype-specific gene signature might be reversible phenomenon. SECONDARY CATEGORY: Neuropathology & Tumor Biomarkers.
Association of Timing of Surgery for Hip Fracture and Patient Outcomes
Authors: Gretchen M. Orosz
Journal: JAMA (2004)

ContextPrevious studies of surgical timing in patients with hip fracture have yielded conflicting findings on mortality and have not focused on functional outcomes.ObjectiveTo examine the association of timing of surgical repair of hip fracture with function and other outcomes.DesignProspective cohort study including analyses matching cases of early (≤24 hours) and late (&gt;24 hours) surgery with propensity scores and excluding patients who might not be candidates for early surgery.SettingFour hospitals in the New York City metropolitan area.ParticipantsA total of 1206 patients aged 50 years or older admitted with hip fracture over 29 months, ending December 1999.Main Outcome MeasuresFunction (using the Functional Independence Measure), survival, pain, and length of stay (LOS).ResultsOf the patients treated with surgery (n = 1178), 33.8% had surgery within 24 hours. Earlier surgery was not associated with improved mortality (hazard ratio, 0.75; 95% confidence interval [CI], 0.52-1.08) or improved locomotion (difference of −0.04 points; 95% CI, –0.49 to 0.39). Earlier surgery was associated with fewer days of severe and very severe pain (difference of −0.22 days; 95% CI, −0.41 to −0.03) and shorter LOS by 1.94 days (P&lt;.001), but postoperative pain and LOS after surgery did not differ. Analyses with propensity scores yielded similar results. When the cohort included only patients who were medically stable at admission and therefore eligible for early surgery, the results were unchanged except that early surgery was associated with fewer major complications (odds ratio, 0.26; 95% CI, 0.07-0.95).ConclusionsEarly surgery was not associated with improved function or mortality, but it was associated with reduced pain and LOS and probably major complications among patients medically stable at admission. Additional research is needed on whether functional outcomes may be improved. In the meantime, patients with hip fracture who are medically stable should receive early surgery when possible.
OTX2 loss causes rod differentiation defect in CRX-associated congenital blindness
Authors: Jerome E. Roger, Avinash Hiriyanna, Norimoto Gotoh, Hong Hao, Debbie F. Cheng, Rinki Ratnapriya, Marie-Audrey I. Kautzmann, Bo Chang, Anand Swaroop
Journal: Journal of Clinical Investigation (2014)

Leber congenital amaurosis (LCA) encompasses a set of early-onset blinding diseases that are characterized by vision loss, involuntary eye movement, and nonrecordable electroretinogram (ERG). At least 19 genes are associated with LCA, which is typically recessive; however, mutations in homeodomain transcription factor CRX lead to an autosomal dominant form of LCA. The mechanism of CRX-associated LCA is not understood. Here, we identified a spontaneous mouse mutant with a frameshift mutation in Crx (CrxRip). We determined that CrxRip is a dominant mutation that results in congenital blindness with nonrecordable response by ERG and arrested photoreceptor differentiation with no associated degeneration. Expression of LCA-associated dominant CRX frameshift mutations in mouse retina mimicked the CrxRip phenotype, which was rescued by overexpression of WT CRX. Whole-transcriptome profiling using deep RNA sequencing revealed progressive and complete loss of rod differentiation factor NRL in CrxRip retinas. Expression of NRL partially restored rod development in CrxRip/+ mice. We show that the binding of homeobox transcription factor OTX2 at the Nrl promoter was obliterated in CrxRip mice and ectopic expression of OTX2 rescued the rod differentiation defect. Together, our data indicate that OTX2 maintains Nrl expression in developing rods to consolidate rod fate. Our studies provide insights into CRX mutation-associated congenital blindness and should assist in therapeutic design.
Effects of Biomechanical Properties of the Bone–Implant Interface on Dental Implant Stability: From In Silico Approaches to the Patient's Mouth
Authors: Guillaume Haïat, Hom-Lay Wang, John Brunski
Journal: Annual Review of Biomedical Engineering (2014)

Dental implants have become a routinely used technique in dentistry for replacing teeth. However, risks of failure are still experienced and remain difficult to anticipate. Multiscale phenomena occurring around the implant interface determine the implant outcome. The aim of this review is to provide an understanding of the biomechanical behavior of the interface between a dental implant and the region of bone adjacent to it (the bone–implant interface) as a function of the interface's environment. First, we describe the determinants of implant stability in relation to the different multiscale simulation approaches used to model the evolution of the bone–implant interface. Then, we review the various aspects of osseointegration in relation to implant stability. Next, we describe the different approaches used in the literature to measure implant stability in vitro and in vivo. Last, we review various factors affecting the evolution of the bone–implant interface properties.
Myasthenia gravis. CD4+ T epitopes on the embryonic gamma subunit of human muscle acetylcholine receptor.
Authors: M P Protti, A A Manfredi, X D Wu, L Moiola, M W Dalton, J F Howard, B M Conti-Tronconi
Journal: Journal of Clinical Investigation (1992)

In myasthenia gravis (MG) an autoimmune response against muscle acetylcholine receptor (AChR) occurs. Embryonic muscle AChR contains a gamma subunit, substituted in adult muscle by a homologous epsilon subunit. Antibodies and CD4+ cells specific for embryonic AChR have been demonstrated in MG patients. We identified sequence segments of the human gamma subunit forming epitopes recognized by four embryonic AChR-specific CD4+ T cell lines, propagated from MG patients' blood by stimulation with synthetic peptides corresponding to the human gamma subunit sequence. Each line had an individual epitope repertoire, but two 20-residue sequence regions were recognized by three lines of different HLA haplotype. Most T epitope sequences were highly diverged between the gamma and the other AChR subunits, confirming the specificity of the T cells for embryonic AChR. These T cells may have been sensitized against AChR expressed by a tissue other than innervated skeletal muscle, possibly the thymus, which expresses an embryonic muscle AChR-like protein, containing a gamma subunit. Several sequence segments forming T epitopes are similar to regions of microbial and/or mammalian proteins unrelated to the AChR. These findings are consistent with the possibility that T cell cross-reactivity between unrelated proteins ("molecular mimicry"), proposed as a cause of autoimmune responses, is not a rare event.
AID-dependent histone acetylation is detected in immunoglobulin S regions
Authors: Lili Wang, Naree Whang, Robert Wuerffel, Amy L. Kenter
Journal: The Journal of Experimental Medicine (2006)

Class switch recombination (CSR) is regulated by the expression of activation-induced deaminase (AID) and germline transcripts (GLTs). AID-dependent double-strand breaks (DSBs) are introduced into switch (S) regions and stimulate CSR. Although histone acetylation (Ac) has been well documented in transcription regulation, its role in DNA damage repair remains largely unexplored. The 1B4.B6 B cell line and normal splenic B cells were activated to undergo CSR and analyzed for histone Ac by chromatin immunoprecipitation (ChIP). A detailed study of the Iγ3-Sγ3-Cγ3 locus demonstrated that acetylated histones are focused to the Iγ3 exon and the Sγ3 region but not to the intergenic areas. Histone H3 Ac is strongly correlated with GLT expression at four S regions, whereas H4 Ac was better associated with B cell activation and AID expression. To more directly examine the relationship between H4 Ac and AID, LPS-activated AID KO and WT B cells were analyzed and express comparable levels of GLTs. In AID-deficient B cells, both histones H3 and H4 are reduced where H4 is more severely affected as compared with WT cells. Our findings raise the intriguing possibility that histone H4 Ac at S regions is a marker for chromatin modifications associated with DSB repair during CSR.
CD28 Costimulation Provided through a CD19-Specific Chimeric Antigen Receptor Enhances<i>In vivo</i>Persistence and Antitumor Efficacy of Adoptively Transferred T Cells
Authors: Claudia M. Kowolik, Max S. Topp, Sergio Gonzalez, Timothy Pfeiffer, Simon Olivares, Nancy Gonzalez, David D. Smith, Stephen J. Forman, Michael C. Jensen, Laurence J.N. Cooper
Journal: Cancer Research (2006)

Abstract Chimeric antigen receptors (CAR) combine an antigen-binding domain with a CD3-ζ signaling motif to redirect T-cell specificity to clinically important targets. First-generation CAR, such as the CD19-specific CAR (designated CD19R), may fail to fully engage genetically modified T cells because activation is initiated by antigen-dependent signaling through chimeric CD3-ζ, independent of costimulation through accessory molecules. We show that enforced expression of the full-length costimulatory molecule CD28 in CD8+CD19R+CD28− T cells can restore fully competent antigen-dependent T-cell activation upon binding CD19+ targets expressing CD80/CD86. Thus, to provide costimulation to T cells through a CD19-specific CAR, independent of binding to CD80/CD86, we developed a second-generation CAR (designated CD19RCD28), which includes a modified chimeric CD28 signaling domain fused to chimeric CD3-ζ. CD19R+ and CD19RCD28+ CD8+ T cells specifically lyse CD19+ tumor cells. However, the CD19RCD28+ CD8+ T cells proliferate in absence of exogenous recombinant human interleukin-2, produce interleukin-2, propagate, and up-regulate antiapoptotic Bcl-XL after stimulation by CD19+ tumor cells. For the first time, we show in vivo that adoptively transferred CD19RCD28+ T cells show an improved persistence and antitumor effect compared with CD19R+ T cells. These data imply that modifications to the CAR can result in improved therapeutic potential of CD19-specific T cells expressing this second-generation CAR. (Cancer Res 2006; 66(22): 10995-1004)
Randomized Phase III Study of Fludarabine Phosphate Versus Cyclophosphamide, Vincristine, and Prednisone in Patients With Recurrent Low-Grade Non-Hodgkin’s Lymphoma Previously Treated With an Alkylating Agent or Alkylator-Containing Regimen
Authors: Richard J. Klasa, Ralph M. Meyer, Chaim Shustik, Carol A. Sawka, Anne Smith, Raymond Guévin, Andrew Maksymiuk, Morel Rubinger, Martin Samosh, Suzanne Laplante, Jean-François Grenier
Journal: Journal of Clinical Oncology (2002)

PURPOSE: To compare in a phase III study the safety and efficacy of fludarabine to that of cyclophosphamide, vincristine, and prednisone (CVP) in recurrent, low-grade, non-Hodgkin’s lymphoma after previous response to systemic treatment. PATIENTS AND METHODS: Patients were randomized to fludarabine (25 mg/m 2 intravenously on days 1 to 5, every 28 days) or CVP (cyclophosphamide 750 mg/m 2 and vincristine 1.2 mg/m 2 both intravenously on day 1 and prednisone 40 mg/m 2 orally on days 1 to 5, every 21 days). The primary outcome assessed was progression-free survival (PFS); secondary outcomes included treatment-free survival (TFS), overall survival (OS), treatment-related toxicity, and quality of life (QoL) according to the European Organization for Research and Treatment of Cancer’s Quality of Life Questionnaire C-30 version 1.0 instrument. RESULTS: Ninety-one patients were randomized, 47 to fludarabine and 44 to CVP. There was no difference in response rates, with 64% (complete response [CR], 9%) for fludarabine versus 52% (CR, 7%) for CVP (P = .72). With a median follow-up of 42 months, median PFS (11 months v 9.1 months; P = .03) and TFS (15 months v 11 months; P = .02) were superior in patients receiving fludarabine. No difference in median overall survival was detected (57 months for fludarabine v 44 months for CVP; P = .95). Three patients receiving fludarabine died of treatment-related toxicity compared with none of the patients receiving CVP. Peripheral neuropathy and alopecia were more common with CVP. Patients receiving fludarabine had higher scores for social function (P = .008); no other differences in QoL were detected. CONCLUSION: In recurrent low-grade lymphoma, fludarabine improves PFS, TFS, and social function scores in comparison with CVP but does not improve OS.
Characteristics of asthma in the elderly
Authors: P Weiner, R Magadle, J Waizman, M Weiner, M Rabner, D Zamir
Journal: European Respiratory Journal (1998)

Asthma occurs more frequently in the elderly than is usually appreciated and may, therefore, be underdiagnosed and undertreated. This study evaluated the relationship between asthma symptoms and the degree of airflow obstruction in elderly and young asthmatics. Fifteen young asthmatics (&lt;65 yrs) (group A), 15 aged &gt;65 yrs with onset of symptoms before 65 yrs (group B), and 15 aged &gt;65 yrs with onset of symptoms after 65 yrs (group C), were studied. Patients used daily diary cards, during 2 weeks, to record inhaled beta2-agonist consumption and severity of asthma symptoms. Long-standing asthma was associated with a significantly lower forced expiratory volume in one second as compared with recent onset asthma. The asthma-symptom score was highest in group A, lower in group B and significantly lower in group C. When symptoms were related to the degree of obstruction (asthma index), it was higher in the young asthmatics than in both groups of elderly patients. In conclusion, elderly patients with long-standing asthma had more severe airway obstruction than patients with recently acquired disease. Older patients particularly those with long-standing disease complained less about asthma symptoms. Within the various groups of patients, subjective symptoms of asthma were negatively related to asthma duration.
Cryopreservation of hematopoietic stem cells
Authors: David Berz, Elise M. McCormack, Eric S. Winer, Gerald A. Colvin, Peter J. Quesenberry
Journal: American Journal of Hematology (2007)

Abstract Stem cell transplantation represents a critical approach for the treatment of many malignant and non‐malignant diseases. The foundation for these approaches is the ability to cryopreserve marrow cells for future use. This technique is routinely employed in all autologous settings and is critical for cord blood transplantation. A variety of cryopreservatives have been used with multiple freezing and thawing techniques as outlined in the later chapters. Freezing efficiency has been proven repeatedly and the ability of long‐term stored marrow to repopulate has been established. Standard approaches outlined here are used in many labs as the field continues to evolve. Am. J. Hematol., 2007. © 2007 Wiley‐Liss, Inc.
Survivin: Key Regulator of Mitosis and Apoptosis and Novel Target for Cancer Therapeutics
Authors: Alain C. Mita, Monica M. Mita, Steffan T. Nawrocki, Francis J. Giles
Journal: Clinical Cancer Research (2008)

Abstract Survivin, a member of the family of inhibitor of apoptosis proteins, functions as a key regulator of mitosis and programmed cell death. Initially, survivin was described as an inhibitor of caspase-9. However, over the last years, research studies have shown that the role of survivin in cancer pathogenesis is not limited to apoptosis inhibition but also involves the regulation of the mitotic spindle checkpoint and the promotion of angiogenesis and chemoresistance. Survivin gene expression is transcriptionally repressed by wild-type p53 and can be deregulated in cancer by several mechanisms, including gene amplification, hypomethylation, increased promoter activity, and loss of p53 function. This article reviews the multiple functions of survivin in the regulation of apoptosis, the promotion of tumorigenesis, and the development of survivin inhibitors as a novel anticancer therapeutic strategy.