bluuebunny/crossref_metadata_2025_split huggingface dataset:
Functional Connectivity Networks in Nonbothersome Tinnitus
Authors: Wineland Andre M. , Burton Harold , Piccirillo Jay 
Published: June 2012

ObjectiveTo assess functional connectivity in cortical networks in patients with nonbothersome tinnitus compared with a normal healthy nontinnitus control group by measuring low‐frequency (<0.1 Hz) spontaneous blood oxygenation level–dependent (BOLD) signals at rest.DesignCase‐control.SettingAcademic medical center.ParticipantsNonbothersome, idiopathic subjective tinnitus for at least 6 months (n = 18) and a normal healthy nontinnitus control group (n = 23).Main Outcome MeasureFunctional connectivity differences in 58 a priori selected seed regions of interest encompassing cortical loci in the default mode, attention, auditory, visual, somatosensory, and cognitive networks.ResultsThe median age of the 18 subjects was 54 years (interquartile range [IQR], 52‐57), 66% were male, 90% were white, median Tinnitus Handicap Inventory (THI) score was 8 (IQR, 4‐14), and a median Beck Depression Index score was 1 (IQR, 0‐5). The median age for the control group was 46 years (IQR, 39‐54), and 52% were male. Of the 58 seeds analyzed, no regions had significantly different functional connectivity among the nonbothersome tinnitus group when compared with the control group.ConclusionAmong nonbothersome tinnitus patients, the tinnitus percept does not appear to alter the functional connectivity of the auditory cortex or other key cortical regions.Trial RegistrationClinicalTrials.gov Identifier: NCT01049828
Enforced expression of Lin28b leads to impaired T-cell development, release of inflammatory cytokines, and peripheral T-cell lymphoma
Authors: Beachy Sarah H. , Onozawa Masahiro , Chung Yang Jo , Slape Chris , Bilke Sven , Francis Princy , Pineda Marbin , Walker Robert L. , Meltzer Paul , Aplan Peter D. 
Published: June 2012

Abstract
LIN28A and LIN28B, the mammalian homologs of lin-28, are implicated in malignant transformation in part because of their ability to promote degradation of the let-7 family of miRs. In the present study, we show that overexpression of Lin28b in vivo leads to an aggressive peripheral T-cell lymphoma (PTCL) characterized by widespread infiltration of parenchymal organs with malignant CD4+ cells. Similar to patients with PTCL, Lin28b-transgenic mice show signs of inflammation such as eosinophilia, increased C-reactive protein, release of inflammatory cytokines, and pleural effusion. The PTCLs that develop in Lin28b mice are derived from activated T cells and show decreased let-7 expression, increased Il6 expression, activation of NF-κB, and infiltration of B cells, all resulting in an inflammatory microenvironment. In addition, LIN28B is overexpressed 7.5-fold in PTCL patient samples compared with activated CD4+ cells. The results of the present study demonstrate for the first time that Lin28b can transform primary cells in vivo, identify a previously unsuspected link between Lin28b and PTCL, and provide a unique animal model for the study of PTCL biology and therapy.
Anti-CD3ε mAb improves thymic architecture and prevents autoimmune manifestations in a mouse model of Omenn syndrome: therapeutic implications
Authors: Marrella Veronica , Poliani Pietro L. , Fontana Elena , Casati Anna , Maina Virginia , Cassani Barbara , Ficara Francesca , Cominelli Manuela , Schena Francesca , Paulis Marianna , Traggiai Elisabetta , Vezzoni Paolo , Grassi Fabio , Villa Anna 
Published: June 2012

AbstractOmenn syndrome (OS) is an atypical primary immunodeficiency characterized by severe autoimmunity because of activated T cells infiltrating target organs. The impaired recombinase activity in OS severely affects expression of the pre-T-cell receptor complex in immature thymocytes, which is crucial for an efficient development of the thymic epithelial component. Anti-CD3ε monoclonal antibody (mAb) treatment in RAG2−/− mice was previously shown to mimic pre-TCR signaling promoting thymic expansion. Here we show the effect of anti-CD3ε mAb administration in the RAG2R229Q mouse model, which closely recapitulates human OS. These animals, in spite of the inability to induce the autoimmune regulator, displayed a significant amelioration in thymic epithelial compartment and an important reduction of peripheral T-cell activation and tissue infiltration. Furthermore, by injecting a high number of RAG2R229Q progenitors into RAG2−/− animals previously conditioned with anti-CD3ε mAb, we detected autoimmune regulator expression together with the absence of peripheral immunopathology. These observations indicate that improving epithelial thymic function might ameliorate the detrimental behavior of the cell-autonomous RAG defect. Our data provide important therapeutic proof of concept for future clinical applications of anti-CD3ε mAb treatment in severe combined immunodeficiency forms characterized by poor thymus function and autoimmunity.
Stat3: linking inflammation to epithelial cancer - more than a "gut" feeling?
Authors: Jarnicki Andrew , Putoczki Tracy , Ernst Matthias 
Published: June 2012

AbstractInflammation is an important environmental factor that promotes tumourigenesis and the progression of established cancerous lesions, and recent studies have started to dissect the mechanisms linking the two pathologies. These inflammatory and infectious conditions trigger immune and stromal cell release of soluble mediators which facilitate survival and proliferation of tumour cells in a paracrine manner. In addition, (epi-)genetic mutations affecting oncogenes, tumour-suppressor genes, chromosomal rearrangements and amplifications trigger the release of inflammatory mediators within the tumour microenvironment to promote neoplastic growth in an autocrine manner. These two pathways converge in tumour cells and result in activation of the latent signal transducer and activator of transcription 3 (Stat3) which mediates a transcriptional response favouring survival, proliferation and angiogenesis. The abundance of cytokines that activate Stat3 within the tumour microenvironment, which comprises of members of the interleukin (IL) IL6, IL10 and IL17/23 families, underpins a signaling network that simultaneously promotes the growth of neoplastic epithelium, fuels inflammation and suppresses the host's anti-tumour immune response. Accordingly, aberrant and persistent Stat3 activation is a frequent observation in human cancers of epithelial origin and is often associated with poor outcome.Here we summarize insights gained from mice harbouring mutations in components of the Stat3 signaling cascade and in particular of gp130, the shared receptor for the IL6 family of cytokines. We focus on the various feed-back and feed-forward loops in which Stat3 provides the signaling node in cells of the tumour and its microenvironment thereby functionally linking excessive inflammation to neoplastic growth. Although these observations are particularly pertinent to gastrointestinal tumours, we suggest that the tumour's addiction to persistent Stat3 activation is likely to also impact on other epithelial cell-derived cancers. These insights provide clues to the judicious interference of the gp130/Stat3 signaling cascade in therapeutically targeting cancer.
Ovarian Function and Reproductive Hormone Levels in Girls with Prader-Willi Syndrome: A Longitudinal Study
Authors: Siemensma Elbrich P. C. , van Alfen-van der Velden A. A. E. M. (Janielle) , Otten Barto J. , Laven Joop S. E. , Hokken-Koelega Anita C. S. 
Published: June 2012

Context:The etiology of hypogonadism in girls with Prader-Willi syndrome (PWS) remains uncertain.Objectives:The aim of the study was to evaluate gonadal function longitudinally in girls and female adolescents with PWS.Measurements:We performed a longitudinal assessment of anti-Müllerian hormone (AMH), gonadotropins, estradiol (E2), inhibin B and A, and pubertal development in girls and female adolescents with PWS.Patients and Methods:Sixty-one girls participating in the Dutch PWS Cohort study participated in the study. Serum AMH, gonadotropins, E2, and inhibin B and A levels were compared with reference values.Results:AMH levels in girls and female adolescents with PWS were comparable to reference levels between 6 months and 22 yr of age. From 10 yr of age, FSH and LH levels increased to above the 5th percentile compared to reference levels. E2 and inhibin B levels were in the low normal range in the majority, and inhibin A levels were low but detectable in almost half the female adolescents with PWS. The median age at puberty onset was comparable, but the median ages at attaining Tanner M3 (P = 0.05) and M4 (P &lt; 0.0001) were significantly higher in girls with PWS than in healthy references.Conclusion:Our study shows that the primordial follicle pool and number of small antral follicles are conserved in girls and female adolescents with PWS. We found no classical hypogonadotropic hypogonadism. However, maturation of follicles and progression of pubertal development are impaired, which might be due to dysregulation of LH secretion. Because these impairments are not absolute, ovulation and thus conception cannot be ruled out in individual female adolescents with PWS.
Chemical Biology of Natural Products on the Basis of Identification of Target Proteins
Authors: Ueda Minoru 
Published: June 2012

Abstract
Recent progress in chemical biology research has accelerated the target protein identification of biologically active small molecules, including naturally occurring ligands. It is widely recognized that a biologically active natural product functions as a “key” that fits a specific protein “lock.” However, recent studies have revealed multiligandable nature of natural products that works as “multiple keys” (or a “master key”) fitting multiple “locks” in a biological event. Biological experiments using natural products as ligands have often provided puzzling results, which can likely be attributed to their multiligandability. Thus, a novel research direction dealing with multiliganbale natural product ligand based on their target identification is strongly desired. This review focuses on the current status of natural products chemistry based on their target identification, and suggest the future direction, named chemical biological chemistry (Chem-Bio-Chem).
Synthesis of Triple-ringed [14]Arene via Dynamic Covalent Chemistry Mechanism in Condensation Reaction of Phenols with m-Benzenedicarbaldehyde
Authors: Seki Hiroyuki , Kuwabara Shingo , Kudo Hiroto , Nishikubo Tadatomi 
Published: June 2012

Abstract
Condensation reaction of 2-methylresorcinol with m-benzenedicarbaldehyde in the presence of HCl as a catalyst in n-propanol at 90 °C for 48 h proceeded via a dynamic covalent chemistry (DCC) mechanism to afford a triple-ringed [14]arene in 52% yield.
Epidemiology of end-stage renal disease in the countries of the Gulf Cooperation Council: a systematic review
Authors: Hassanien Amal A. , Al-Shaikh Fahdah , Vamos Eszter P. , Yadegarfar Ghasem , Majeed Azeem 
Published: June 2012

Objectives To describe the epidemiology of end stage renal disease (ESRD). Design Mixed-methods systematic review. Setting The countries of the Gulf Cooperation Council (GCC) which consist of Saudi Arabia, the United Arab Emirates, Kuwait, Qatar, Bahrain, and Oman. Participants Defined to have ESRD or patients on regular dialysis for a minimum dialysis period of at least three months. Since many outcomes were reviewed, studies that estimated the incidence and prevalence of ESRD as outcomes should not have defined the study population as ESRD population or patients on regular dialysis. Studies where the study population mainly comprised children or pregnant woman were excluded. Main outcome measures The trends of the incidence, prevalence, and mortality rate of ESRD; also, causes of mortality, primary causes and co-morbid conditions associated with ESRD. Results 44 studies included in this review show that the incidence of ESRD has increased while the prevalence and mortality rate of ESRD in the GCC has not been reported sufficiently. The leading primary causes of ESRD recorded in the countries of the GCC is diabetes with the most prevalent co-morbid conditions being Hypertension and Hepatitis C Virus infection; the most common cause of death was cardiovascular disease and sepsis. Conclusions This review highlights that the lack of national renal registries data is a critical issue in the countries of the GCC. The available data also do not provide an accurate and updated estimate for relevant outcomes. Additionally, considering the increasing burden of chronic kidney disease (CKD), these results stressed the needs and the importance of preventative strategies for leading causes of ESRD. Furthermore, more studies are needed to describe the epidemiology of ESRD and for assessing the overall quality of renal care.
Thrombus load and acute right ventricular failure in pulmonary embolism: correlation and demonstration of a “tipping point” on CT pulmonary angiography
Authors: Wong L F , Akram A R , Mcgurk S , Van Beek E J R , Reid J H , Murchison J T 
Published: June 2012

Objectives
The aim of this study was to determine the correlation between increasing pulmonary embolism thrombus load and right ventricular (RV) dilatation as demonstrated by CT pulmonary angiography (CTPA) and to assess the thrombus load threshold which indicates impending RV decompensation.

Methods
2425 consecutive CTPAs were retrospectively analysed. Thrombus load using a modified Miller score (MMS), RV to left ventricular (RV:LV) ratio, presence of septal shift, and pulmonary artery and aorta size were analysed in 504 positive CTPA scans and a representative cohort of 100 negative scans. Results were correlated using non-parametric analysis (two-tailed t-test or χ 2 test) and Pearson’s rank correlation.

Results
Increasing thrombus load correlated with a higher RV:LV ratio, with a statistically significant difference in RV:LV ratios between the negative and positive pulmonary embolism (PE) cohorts. Larger thrombus loads (MMS ≥12 vs MMS &lt;12) were strongly correlated with RV strain (mean RV:LV ratio, 1.323 vs 0.930; p&lt;0.0001). Smaller thrombus loads had no significant influence on RV strain. Septal shift was also more likely with an MMS of ≥12, as was an increase in pulmonary artery diameter (r=0.221, p&lt;0.001).

Conclusion
With increasing thrombus load in PE, there is CTPA evidence of RV decompensation with an MMS threshold of 12. This suggests a “tipping point” beyond which RV decompensation is more likely to occur. This is the first study to describe this tipping point between a thrombus load of MMS &gt;12 and an increase in RV:LV ratio. This finding may help to improve risk stratification in patients with acute PE diagnosed by CTPA.
Nano- and microstructures in stretched and non-stretched blend gels of cellulose and hemicelluloses
Authors: Roubroeks Johannes P. , Kondo Tetsuo 
Published: June 2012

Abstract
Molecular interactions between cellulose and hemicelluloses, such as xyloglucan and xylan, play an important role in the formation of ordered layers in the cell wall of higher plants. This study attempts to characterize an ordered state of a matrix consisting of cellulose and hemicellulose induced by stretching never-dried binary blended films. In non-stretched films, the xylan component easily adapted into the semicrystalline state, while the xyloglucan component remained amorphous. Once both blended films were stretched, each component tended to be close enough to the adherent macromolecule, and the interaction resulted in typical morphological orders at the nano- and microscale levels. These studies could be useful in constructing new bio-derived materials, as well as understanding the molecular interactions between the polymers.
Pretreatment of softwood dissolving pulp with ionic liquids
Authors: Li Dongfang , Sevastyanova Olena , Ek Monica 
Published: June 2012

Abstract
Few Scandinavian pulp mills produce dissolving pulps; however, the demand on textile fibers is increasing. This study investigates the chemical interaction of dissolving pulp with ionic liquids (ILs), where softwood and hardwood industrial dissolving pulps were pretreated with ILs 1-butyl-3-methy-limidazolium acetate ([C4mim+]CH3COO-) and 1-butyl-3-methyl-imdazolium chloride ([C4mim+]Cl-). Time and temperature dependence of the dissolution process as well as the impact of the pretreatment on the molecular weight properties, thermal stability, morphology, and crystallinity of the cellulose were evaluated by means of size exclusion chromatography (SEC), thermogravimetric analysis (TGA), scanning electron microscopy (SEM), X-ray diffraction (XRD), and solid state nuclear magnetic resonance (NMR). It was shown that the dissolution of cellulosic material in ILs is a temperature-dependent process; however, the viscosity of ILs affected the efficiency of dissolution at a given temperature. Molecular weight properties were affected negatively by increased dissolution temperature, while the type of antisolvent for the regeneration had no major impact on the degree of polymerization of cellulose. Water was more efficient than ethanol for the regeneration of cellulose when performed at an elevated temperature. The pretreatment decreased the crystallinity of cellulosic material. This might lead to the increased accessibility and reactivity of cellulose.
A posteriori error analysis for unstable models
Authors: Bakushinsky Anatoly B. , Smirnova Alexandra , Liu Hui 
Published: June 2012

Abstract.
In this paper, we consider the possibility of a posteriori error estimates for linear and nonlinear ill-posed operator equations.
Given an auxiliary finite-dimensional problem ,
that approximates the original infinite model , with a certain level of accuracy,
we try to estimate the distance between z, an approximate solution to , and , the exact solution to . The problem
is assumed to accumulate different sources of error (discretization, measurements, etc.), and the computed solution z is assumed to satisfy the equation
within a nonzero tolerance .
We conduct both a theoretical and numerical study of a posteriori error analysis.
A Pragmatic Approach to More Efficient Corporate Disclosure
Authors: Bloomfield Robert J. 
Published: June 2012

SYNOPSIS
This paper uses a Pragmatic theory of language (drawn from philosophy and linguistics) to diagnose the causes of excessive financial disclosure and propose a regulatory solution. The diagnosis is that existing disclosure regulations are one sided, effectively encouraging firms to disclose any information that might be relevant, but failing to discourage disclosure of information that adds little to what investors already know. This one-sidedness limits investors' ability to draw inferences that items the firm chooses not to disclose are not newsworthy (an inference Pragmatic theorists call “implicature”). The solution is to encourage or require firms to supplement comprehensive disclosures with an “elevated” disclosure that is brief enough to force firms to be selective in choosing what information to include. Regulations can enhance implicature through rules that prohibit firms from elevating disclosures that are less newsworthy than disclosures that are not elevated.
The Role of Accounting in the Financial Crisis: Lessons for the Future
Authors: Kothari S. P. , Lester Rebecca 
Published: June 2012

SYNOPSIS
The advent of the Great Recession in 2008 was the culmination of a perfect storm of lax regulation, a growing housing bubble, rising popularity of derivatives instruments, and questionable banking practices. In addition to these causes, management incentives as well as certain U.S. accounting standards contributed to the financial crisis. We outline the significant effects of these incentive structures and the role of fair value accounting standards during the crisis, and discuss implications and relevance of these rules to practitioners, standard-setters, and academics.
β-Cell Function Preservation After 3.5 Years of Intensive Diabetes Therapy
Authors: Harrison Lindsay B. , Adams-Huet Beverley , Raskin Philip , Lingvay Ildiko 
Published: June 2012

OBJECTIVE
To assess β-cell function preservation after 3.5 years of intensive therapy with insulin plus metformin (INS group) versus triple oral therapy (TOT group) with metformin, glyburide, and pioglitazone.

RESEARCH DESIGN AND METHODS
This was a randomized trial of 58 patients with treatment-naïve newly diagnosed type 2 diabetes. All patients were treated with insulin and metformin for a 3-month lead-in period followed by random assignment to the INS or TOT group. β-Cell function was assessed using a mixed-meal challenge test at randomization and 6, 12, 18, 30, and 42 months. Analyses were intention to treat and performed with repeated-measures models.

RESULTS
Completion rates at 3.5 years were 83% in the insulin group and 72% in the TOT group, with good compliance in both groups (87 ± 20% in the INS group vs. 90 ± 15% in the TOT group). β-Cell function was preserved at 3.5 years after diagnosis, with no significant change from baseline or difference between the two groups as measured by area under the curve (AUC) of C-peptide (P = 0.14) or the ratio of C-peptide to glucose AUC (P = 0.7). Excellent glycemic control was maintained in both groups (end-of-study HbA1c 6.35 ± 0.84% in the INS group vs. 6.59 ± 1.94% in the TOT group). Weight increased in both groups over time (from 102.2 ± 24.9 kg to 106.2 ± 31.7 kg in the INS group and from 100.9 ± 23.0 kg to 110.5 ± 31.8 kg in the TOT group), with no significant difference between groups (P = 0.35). Hypoglycemic events decreased significantly over time (P = 0.01) but did not differ between groups (P = 0.83).

CONCLUSIONS
β-Cell function can be preserved for at least 3.5 years with early and intensive therapy for type 2 diabetes with either insulin plus metformin or triple oral therapy after an initial 3-month insulin-based treatment period.
Intensive Glycemic Control Is Not Associated With Fractures or Falls in the ACCORD Randomized Trial
Authors: Schwartz Ann V. , Margolis Karen L. , Sellmeyer Deborah E. , Vittinghoff Eric , Ambrosius Walter T. , Bonds Denise E. , Josse Robert G. , Schnall Adrian M. , Simmons Debra L. , Hue Trisha F. , Palermo Lisa , Hamilton Bruce P. , Green Jennifer B. , Atkinson Hal H. , O’Connor Patrick J. , Force Rex W. , Bauer Douglas C. 
Published: June 2012

OBJECTIVE
Older adults with type 2 diabetes are at high risk of fractures and falls, but the effect of glycemic control on these outcomes is unknown. To determine the effect of intensive versus standard glycemic control, we assessed fractures and falls as outcomes in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) randomized trial.

RESEARCH DESIGN AND METHODS
ACCORD participants were randomized to intensive or standard glycemia strategies, with an achieved median A1C of 6.4 and 7.5%, respectively. In the ACCORD BONE ancillary study, fractures were assessed at 54 of the 77 ACCORD clinical sites that included 7,287 of the 10,251 ACCORD participants. At annual visits, 6,782 participants were asked about falls in the previous year.

RESULTS
During an average follow-up of 3.8 (SD 1.3) years, 198 of 3,655 participants in the intensive glycemia and 189 of 3,632 participants in the standard glycemia group experienced at least one nonspine fracture. The average rate of first nonspine fracture was 13.9 and 13.3 per 1,000 person-years in the intensive and standard groups, respectively (hazard ratio 1.04 [95% CI 0.86–1.27]). During an average follow-up of 2.0 years, 1,122 of 3,364 intensive- and 1,133 of 3,418 standard-therapy participants reported at least one fall. The average rate of falls was 60.8 and 55.3 per 100 person-years in the intensive and standard glycemia groups, respectively (1.10 [0.84–1.43]).

CONCLUSIONS
Compared with standard glycemia, intensive glycemia did not increase or decrease fracture or fall risk in ACCORD.