bluuebunny/crossref_metadata_2025_split huggingface dataset:
Two anatomically distinct niches regulate stem cell activity
Authors: Ema Hideo , Suda Toshio 
Published: July 2012

Abstract
The niche microenvironment controls stem cell number, fate, and behavior. The bone marrow, intestine, and skin are organs with highly regenerative potential, and all produce a large number of mature cells daily. Here, focusing on adult stem cells in these organs, we compare the structures and cellular components of their niches and the factors they produce. We then define the niche as a functional unit for stem cell regulation. For example, the niche possibly maintains quiescence and regulates fate in stem cells. Moreover, we discuss our hypothesis that many stem cell types are regulated by both specialized and nonspecialized niches, although hematopoietic stem cells, as an exception, are regulated by a nonspecialized niche only. The specialized niche is composed of 1 or a few types of cells lying on the basement membrane in the epithelium. The nonspecialized niche is composed of various types of cells widely distributed in mesenchymal tissues. We propose that the specialized niche plays a role in local regulation of stem cells, whereas the nonspecialized niche plays a role in relatively broad regional or systemic regulation. Further work will verify this dual-niche model to understand mechanisms underlying stem cell regulation.
A novel SYBR-based duplex qPCR for the detection of gene dosage: detection of an APC large deletion in a familial adenomatous polyposis patient with an unusual phenotype
Authors: Torrezan Giovana Tardin , da Silva Felipe Cavalcanti Carneiro , Krepischi Ana Cristina Victorino , dos Santos Érika Maria Monteiro , Rossi Benedito Mauro , Carraro Dirce Maria 
Published: July 2012

Abstract

Background
Familial adenomatous polyposis (FAP) is a hereditary colorectal cancer syndrome caused by a loss of function of the APC gene. Large deletions in APC are a common cause of FAP; despite the existence of a variety of gene dosage detection methodologies, most are labor intensive and time and resource consuming.

Methods
We describe a new duplex qPCR method for gene dosage analysis based on the coamplification of a target and a reference gene in a SYBR Green reaction, followed by a comparison of the ratio between the target and the reference peaks of the melting curve for the test (patient) and control samples. The reliability of the described duplex qPCR was validated for several genes (APC, HPRT1, ATM, PTEN and BRCA1).

Results
Using this novel gene dosage method, we have identified an APC gene deletion in a FAP patient undergoing genetic testing. Comparative genomic hybridization based on microarrays (aCGH) was used to confirm and map the extent of the deletion, revealing a 5.2 MB rearrangement (5q21.3-q22.3) encompassing the entire APC and 19 additional genes.

Conclusion
The novel assay accurately detected losses and gains of one copy of the target sequences, representing a reliable and flexible alternative to other gene dosage techniques. In addition, we described a FAP patient harboring a gross deletion at 5q21.3-q22.3 with an unusual phenotype of the absence of mental impairment and dysmorphic features.
Identification of BIRC6 as a novel intervention target for neuroblastoma therapy
Authors: Lamers Fieke , Schild Linda , Koster Jan , Speleman Frank , Øra Ingrid , Westerhout Ellen M , van Sluis Peter , Versteeg Rogier , Caron Huib N , Molenaar Jan J 
Published: July 2012

Abstract

Background
Neuroblastoma are pediatric tumors of the sympathetic nervous system with a poor prognosis. Apoptosis is often deregulated in cancer cells, but only a few defects in apoptotic routes have been identified in neuroblastoma.

Methods
Here we investigated genomic aberrations affecting genes of the intrinsic apoptotic pathway in neuroblastoma. We analyzed DNA profiling data (CGH and SNP arrays) and mRNA expression data of 31 genes of the intrinsic apoptotic pathway in a dataset of 88 neuroblastoma tumors using the R2 bioinformatic platform (http://r2.amc.nl). BIRC6 was selected for further analysis as a tumor driving gene. Knockdown experiments were performed using BIRC6 lentiviral shRNA and phenotype responses were analyzed by Western blot and MTT-assays. In addition, DIABLO levels and interactions were investigated with immunofluorescence and co-immunoprecipitation.

Results
We observed frequent gain of the BIRC6 gene on chromosome 2, which resulted in increased mRNA expression. BIRC6 is an inhibitor of apoptosis protein (IAP), that can bind and degrade the cytoplasmic fraction of the pro-apoptotic protein DIABLO. DIABLO mRNA expression was exceptionally high in neuroblastoma but the protein was only detected in the mitochondria. Upon silencing of BIRC6 by shRNA, DIABLO protein levels increased and cells went into apoptosis. Co-immunoprecipitation confirmed direct interaction between DIABLO and BIRC6 in neuroblastoma cell lines.

Conclusion
Our findings indicate that BIRC6 may have a potential oncogenic role in neuroblastoma by inactivating cytoplasmic DIABLO. BIRC6 inhibition may therefore provide a means for therapeutic intervention in neuroblastoma.
Effectiveness of a long-term use of a minimalist footwear versus habitual shoe on pain, function and mechanical loads in knee osteoarthritis: a randomized controlled trial
Authors: Trombini-Souza Francis , Fuller Ricardo , Matias Alessandra , Yokota Mariane , Butugan Marco , Goldenstein-Schainberg Claudia , Sacco Isabel C N 
Published: July 2012

Abstract

Background
Recent studies have shown an important reduction of joint overload during locomotion in elderly women with knee osteoarthritis (OA) after short-term use of minimalist shoes. Our aim is to investigate the chronic effect of inexpensive and minimalist footwear on the clinical and functional aspects of OA and gait biomechanics of elderly women with knee OA.

Methods/Design
Fifty-six elderly women with knee OA grade 2 or 3 (Kellgren and Lawrence) are randomized into blocks and allocated to either the intervention group, which will use flexible, non-heeled shoes— Moleca®—for six months for at least six hours daily, or the control group, which could not use these shoes. Neither group is undergoing physical therapy treatment throughout the intervention period. Moleca® is a women’s double canvas, flexible, flat walking shoe without heels, with a 5-mm anti-slip rubber sole and a 3-mm internal wedge of ethylene vinyl acetate. Both groups will be followed for six months and will be assessed at baseline condition, after three months, and after six months (end of intervention). All the assessments will be performed by a physiotherapist that is blind to the group allocation. The primary outcome is the pain Western Ontario and McMaster Universities Osteoarthritis (WOMAC) score. The secondary outcomes are global WOMAC score; joint stiffness and disability WOMAC scores; knee pain with a visual analogue scale; walking distance in the six-minute walk test; Lequesne score; amount and frequency (number of days) of paracetamol (500 mg) intake over six months; knee adduction moment during gait; global medical assessment score; and global patient auto-assessment score. At baseline, all patients receive a diary to record the hours of daily use of the footwear intervention; every two weeks, the same physiotherapist makes phone calls to all patients in order to verify adherence to treatment. The statistical analysis will be based on intention-to-treat analysis, as well as general linear models of analysis of variance for repeated measure to detect treatment–time interactions (α = 5%).

Discussion
This is the first randomized, clinical trial protocol to assess the chronic effect of minimalist footwear on the clinical and functional aspects and gait biomechanics of elderly women with knee osteoarthritis. We expect that the use of Moleca® shoes for six months will provide pain relief, reduction of the knee adduction moment when walking, and improve joint function in elderly women with knee OA, and that the treatment, thus, can be considered another inexpensive and easy-to-use option for conservative OA treatment.

Trial registration
NCT01342458
Quantum dot-aluminum phthalocyanine conjugates perform photodynamic reactions to kill cancer cells via fluorescence resonance energy transfer
Authors: Li Lei , Zhao Jin-Feng , Won Nayoun , Jin Ho , Kim Sungjee , Chen Ji-Yao 
Published: July 2012

Abstract
Sulfonated aluminum phthalocyanines (AlPcSs), commonly used photosensitizers for photodynamic therapy of cancers (PDT), were conjugated with amine-dihydrolipoic acid-coated quantum dots (QDs) by electrostatic binding, achieving 70 AlPcSs per QD. The AlPcS-QD conjugates can utilize the intense light absorptions of conjugated QDs to indirectly excite AlPcSs producing singlet oxygen via fluorescence resonance energy transfer (FRET), demonstrating a new excitation model for PDT. The AlPcS-QD conjugates easily penetrated into human nasopharyngeal carcinoma cells and carried out the FRET in cells, with efficiency around 80%. Under the irradiation of a 532-nm laser, which is at the absorption region of QDs but not fit for the absorption of AlPcSs, the cellular AlPcS-QD conjugates can destroy most cancer cells via FRET-mediated PDT, showing the potential of this new strategy for PDT.
A Comparative Study of the Effects of Different Chemical Agents on the Pore-Size Distributions of Macadamia Nutshell-Based Activated Carbons Using Different Models
Authors: Okhovat Ahmad , Ahmadpour Ali 
Published: July 2012

The effects of the chemical activation agent and the chemical/nutshell ratio (ranging from 15–500 mass%) on the pore-size distribution (PSD) of macadamia nutshell-based activated carbons have been investigated in this study. The adsorption isotherm data of two series of activated carbons prepared from macadamia nutshell by chemical activation with potassium hydroxide and zinc chloride were used. The three widely used models of Dubinin–Stoeckli, Stoeckli and Horvath–Kawazoe were applied for characterizing these porous solids. Although the results showed some differences amongst these models arising from the fundamental assumptions on which they are based, in general they were comparable. Thus, at the same chemical ratio, samples activated by ZnCl2 showed more adsorption capacity than those from KOH. Moreover, the pore volumes increased as the impregnation ratio in each series increased. In addition, with increasing impregnation ratio (up to 100%) in the ZnCl2 series, the micropores were widened and a further increase in ZnCl2 content caused the micropores to change to mesopores. In the KOH series, increasing KOH created more micropores in the carbon structure over the whole range of chemical/nutshell ratio studied.
Quality Improvement Initiative to Reduce Serious Safety Events and Improve Patient Safety Culture
Authors: Muething Stephen E. , Goudie Anthony , Schoettker Pamela J. , Donnelly Lane F. , Goodfriend Martha A. , Bracke Tracey M. , Brady Patrick W. , Wheeler Derek S. , Anderson James M. , Kotagal Uma R. 
Published: July 2012

BACKGROUND AND OBJECTIVE:
Many thousands of patients die every year in the United States as a result of serious and largely preventable safety events or medical errors. Safety events are common in hospitalized children. We conducted a quality improvement initiative to implement cultural and system changes with the goal of reducing serious safety events (SSEs) by 80% within 4 years at our large, urban pediatric hospital.

METHODS:
A multidisciplinary SSE reduction team reviewed the safety literature, examined recent SSEs, interviewed internal leaders, and visited other leading organizations. Senior hospital leaders provided oversight, monitored progress, and helped to overcome barriers. Interventions focused on: (1) error prevention; (2) restructuring patient safety governance; (3) a new root cause analysis process and a common cause database; (4) a highly visible lessons learned program; and (5) specific tactical interventions for high-risk areas. Our outcome measures were the rate of SSEs and the change in patient safety culture.

RESULTS:
SSEs per 10 000 adjusted patient-days decreased from a mean of 0.9 at baseline to 0.3 (P &lt; .0001). The days between SSEs increased from a mean of 19.4 at baseline to 55.2 (P &lt; .0001). After a worsening of patient safety culture outcomes in the first year of intervention, significant improvements were observed between 2007 and 2009.

CONCLUSIONS:
Our multifaceted approach was associated with a significant and sustained reduction of SSEs and improvements in patient safety culture. Multisite studies are needed to better understand contextual factors and the significance of specific interventions.
Controlled Synthesis of Si Nanopillar Arrays for Photovoltaic and Plasmonic Applications
Authors: Gautam Umesh , Wang Jun , Dachhepati Dilip , Mottaghian Seyyedsadegh , Bayat Khadijeh , Baroughi Mahdi Farrokh 
Published: July 2012

ABSTRACTThis paper focuses on developing a robust process to independently control the geometrical parameters of Si nano-pillar (NP) arrays. These parameters include height and diameter of NPs, spacing between them, and the shape of the NPs. We have shown that the diameter, height, and spacing of NPs can be independently engineered by controlling the diameter of nano-beads through synthesis procedure, duration of isotropic SiO2 etching and duration of anisotropic Si etching, respectively.
Screening and Diagnosis of Gestational Diabetes Mellitus
Authors: Kalter-Leibovici Ofra , Freedman Laurence S. , Olmer Liraz , Liebermann Nicky , Heymann Anthony , Tal Orna , Lerner-Geva Liat , Melamed Nir , Hod Moshe 
Published: July 2012

OBJECTIVE
To study the implications of implementing the International Association of Diabetes in Pregnancy Study Group (IADPSG) recommendations for screening and diagnosis of gestational diabetes mellitus (GDM) in Israel and explore alternative methods for identifying women at risk for adverse pregnancy outcomes.

RESEARCH DESIGN AND METHODS
We analyzed data of the Israeli Hyperglycemia and Adverse Pregnancy Outcomes study participants (N = 3,345). Adverse outcome rates were calculated and compared for women who were positive according to 1) IADPSG criteria, 2) IADPSG criteria with risk stratification, or 3) screening with BMI or fasting plasma glucose (FPG).

RESULTS
Adopting IADPSG recommendations would increase GDM diagnosis by ∼50%. One-third of IADPSG-positive women were at low risk for adverse outcomes and could be managed less intensively. FPG ≥89 mg/dL or BMI ≥33.5 kg/m2 at 28–32 weeks of gestation detected proportions of adverse outcomes similar to IADPSG criteria.

CONCLUSIONS
Implementing IADPSG recommendations will substantially increase GDM diagnosis. Risk stratification in IADPSG-positive women may reduce over-treatment. Screening with FPG or BMI may be a practical alternative.
A Randomized, Controlled Study of Once-Daily LY2605541, a Novel Long-Acting Basal Insulin, Versus Insulin Glargine in Basal Insulin–Treated Patients With Type 2 Diabetes
Authors: Bergenstal Richard M. , Rosenstock Julio , Arakaki Richard F. , Prince Melvin J. , Qu Yongming , Sinha Vikram P. , Howey Daniel C. , Jacober Scott J. 
Published: July 2012

OBJECTIVE
To evaluate whether LY2605541 results in lower fasting blood glucose (FBG) versus insulin glargine (GL).

RESEARCH DESIGN AND METHODS
This 12-week, randomized, open-label, Phase 2 study enrolled patients with type 2 diabetes (hemoglobin A1c [A1C] ≤ 10.5%), taking metformin and/or sulfonylurea with GL or NPH insulin once daily. Patients converted to morning insulin administration during lead-in were randomized 2:1 from GL (n = 248) or NPH insulin (n = 39) to LY2605541 (n = 195) or GL (n = 95) once daily in the morning.

RESULTS
At 12 weeks, FBG (mean ± SE) was similar with LY2605541 and GL (118.2 ± 2.0 mg/dL [6.6 ± 0.1 mmol/L] vs. 116.9 ± 2.7 mg/dL [6.5 ± 0.2 mmol/L], P = 0.433) as was A1C (7.0 ± 0.1 vs. 7.2 ± 0.1%, P = 0.279). Intraday blood glucose variability was reduced with LY2605541 (34.4 vs. 39.1 mg/dL [1.9 vs. 2.2 mmol/L], P = 0.031). LY2605541 patients had weight loss (−0.6 ± 0.2 kg, P = 0.007), whereas GL patients gained weight (0.3 ± 0.2 kg, P = 0.662; treatment difference: −0.8 kg, P = 0.001). The incidence and rate of both total hypoglycemia and nocturnal hypoglycemia were comparable between LY2605541 and GL, although, LY2605541 had a 48% reduction in nocturnal hypoglycemia after adjusting for baseline hypoglycemia (P = 0.021). Adverse events were similar across treatments. Alanine aminotransferase and aspartate aminotransferase remained within normal range but were significantly higher with LY2605541 (P ≤ 0.001).

CONCLUSIONS
In patients with type 2 diabetes, LY2605541 and GL had comparable glucose control and total hypoglycemia rates, but LY2605541 showed reduced intraday variability, lower nocturnal hypoglycemia, and weight loss relative to GL.
Effect of Intensive Multifactorial Treatment Compared With Routine Care on Aortic Stiffness and Central Blood Pressure Among Individuals With Screen-Detected Type 2 Diabetes
Authors: Johansen Nanna B. , Charles Morten , Vistisen Dorte , Rasmussen Signe S. , Wiinberg Niels , Borch-Johnsen Knut , Lauritzen Torsten , Sandbæk Annelli , Witte Daniel R. 
Published: July 2012

OBJECTIVE
Diabetes is associated with increased brachial and central blood pressure and aortic stiffness. We examined the effect of intensive multifactorial treatment in general practice on indices of peripheral and central hemodynamics among patients with screen-detected diabetes.

RESEARCH DESIGN AND METHODS
As part of a population-based screening and intervention study in general practice, 1,533 Danes aged 40–69 years were clinically diagnosed with screen-detected diabetes. General practitioners were randomized to provide intensive multifactorial treatment or routine care. After a mean follow-up of 6.2 years, an unselected subsample of 456 patients underwent central hemodynamic assessments by applanation tonometry. Central pressure was derived from the radial pulse wave. Aortic stiffness was assessed as carotid-femoral pulse wave velocity (aPWV). The intervention effect on each index of central hemodynamics was analyzed by mixed-effects models adjusted for heart rate, cluster randomization, age, and sex.

RESULTS
At screening, median age was 59.2 years (interquartile range 55.2–64.6); 289 patients (63%) were in the intensive treatment group, and 278 patients (61%) were men. Patients in the intensive treatment group had a 0.51 m/s (95% CI −0.96 to −0.05, P = 0.03) lower aPWV compared with routine care. Respective differences for central augmentation index (−0.84% [−2.54 to 0.86]), pulse pressure (0.28 mmHg [−1.75 to 2.32]), and systolic (−1.42 mmHg [−4.47 to 1.64]) and diastolic (−1.79 mmHg [−3.72 to 0.14]) blood pressure were not statistically significant.

CONCLUSIONS
Intensive multifactorial treatment of screen-detected diabetes during 6 years in general practice has a significant impact on aortic stiffness, whereas the effects on other hemodynamic measures are smaller and not statistically significant.
Prognostic Accuracy of Immunologic and Metabolic Markers for Type 1 Diabetes in a High-Risk Population
Authors: Xu Ping , Beam Craig A. , Cuthbertson David , Sosenko Jay M. , Skyler Jay S. , Krischer Jeffrey P. ,   the DPT-1 Study Group
Published: July 2012

OBJECTIVE
To establish and compare the prognostic accuracy of immunologic and metabolic markers in predicting onset of type 1 diabetes in those with high risk in a prospective study.

RESEARCH DESIGN AND METHODS
A total of 339 subjects from the Diabetes Prevention Trial–Type 1 (DPT-1) parenteral study, who were islet cell antibody (ICA)-positive, with low first-phase insulin response (FPIR) and/or abnormal glucose tolerance at baseline, were followed until clinical diabetes onset or study end (5-year follow-up). The prognostic performance of biomarkers was estimated using receiver operating characteristic (ROC) curve analysis and compared with nonparametric testing of ROC curve areas. Pearson correlation was used to assess the relationship between the markers.

RESULTS
Individually, insulin autoantibody titer, ICA512A titer, peak C-peptide, 2-h glucose, FPIR, and FPIR/homeostasis model assessment of insulin resistance provided modest but significant prognostic values for 5-year risk with a similar level of area under ROC curve ranging between 0.61 and 0.67. The combination of 2-h glucose, peak C-peptide, and area under the curve C-peptide significantly improved the prognostic accuracy compared with any solitary index (P &lt; 0.05) with an area under ROC curve of 0.76 (95% CI 0.70–0.81). The addition of antibody titers and/or intravenous glucose tolerance test (IVGTT) markers did not increase the prognostic accuracy further (P = 0.46 and P = 0.66, respectively).

CONCLUSIONS
The combination of metabolic markers derived from the oral glucose tolerance test improved accuracy in predicting progression to type 1 diabetes in a population with ICA positivity and abnormal metabolism. The results indicate that the autoimmune activity may not alter the risk of type 1 diabetes after metabolic function has deteriorated. Future intervention trials may consider eliminating IVGTT measurements as an effective cost-reduction strategy for prognostic purposes.
Health Insurance Coverage Among People With and Without Diabetes in the U.S. Adult Population
Authors: Stark Casagrande Sarah , Cowie Catherine C. 
Published: July 2012

OBJECTIVE
To compare health insurance coverage and type of coverage for adults with and without diabetes.

RESEARCH DESIGN AND METHODS
The data used were from 2,704 adults who self-reported diabetes and 25,008 adults without reported diabetes in the 2009 National Health Interview Survey. Participants reported on their current type of health insurance coverage, demographic information, diabetes-related factors, and comorbidities. If uninsured, participants reported reasons for not having health insurance.

RESULTS
Among all adults with diabetes, 90% had some form of health insurance coverage, including 85% of people 18–64 years of age and ∼100% of people ≥65 years of age; 81% of people without diabetes had some type of coverage (vs. diabetes, P &lt; 0.0001), including 78% of people 18–64 years of age and 99% of people ≥65 years of age. More adults 18–64 years of age with diabetes had Medicare coverage (14% vs. no diabetes, 3%; P &lt; 0.0001); fewer people with diabetes had private insurance (58% vs. no diabetes, 66%; P &lt; 0.0001). People 18–64 years of age with diabetes more often had two health insurance sources compared with people without diabetes (13 vs. 5%, P &lt; 0.0001). The most common private plan was a preferred provider organization (PPO) followed by a health maintenance organization/independent practice organization (HMO/IPA) plan regardless of diabetes status. For participants 18–64 years of age, high health insurance cost was the most common reason for not having coverage.

CONCLUSIONS
Two million adults &lt;65 years of age with diabetes had no health insurance coverage, which has considerable public health and economic impact. Health care reform should work toward ensuring that people with diabetes have coverage for routine care.
Synthesis of 4-Benzo[1,3]Dioxol-5-Ylthieno-[2,3-b]Pyridines
Authors: Grinberga S. , Krauze A. , Krasnova L. , Duburs G. 
Published: July 2012

Synthesis of 4-Benzo[1,3]Dioxol-5-Ylthieno-[2,3-b]Pyridines
4,7-Dihydrothieno[2,3-b]pyridine 4 and thieno[2,3-b]pyridine 6 were obtained by Thorpe-Ziegler cyclization. Mn(OAc)3/acetic acid system had been used for oxidation of 1,4-dihydropyridine 3 to pyridine derivative 5. 6-Carbamoylmethylsulfanyl-1,4-dihydropyridine 3 was prepared by al-kylation of piperidinium 1,4-dihydropyridine-2-thiolate 1 with iodoacet-amide.