bluuebunny/crossref_metadata_2025_split huggingface dataset:
Antibodies Mediate Formation of Neutrophil Extracellular Traps in the Middle Ear and Facilitate Secondary Pneumococcal Otitis Media
Authors: Short Kirsty R. , von Köckritz-Blickwede Maren , Langereis Jeroen D. , Chew Keng Yih , Job Emma R. , Armitage Charles W. , Hatcher Brandon , Fujihashi Kohtaro , Reading Patrick C. , Hermans Peter W. , Wijburg Odilia L. , Diavatopoulos Dimitri A. 
Published: November 2013

ABSTRACT

Otitis media (OM) (a middle ear infection) is a common childhood illness that can leave some children with permanent hearing loss. OM can arise following infection with a variety of different pathogens, including a coinfection with influenza A virus (IAV) and
Streptococcus pneumoniae
(the pneumococcus). We and others have demonstrated that coinfection with IAV facilitates the replication of pneumococci in the middle ear. Specifically, we used a mouse model of OM to show that IAV facilitates the outgrowth of
S. pneumoniae
in the middle ear by inducing middle ear inflammation. Here, we seek to understand how the host inflammatory response facilitates bacterial outgrowth in the middle ear. Using B cell-deficient infant mice, we show that antibodies play a crucial role in facilitating pneumococcal replication. We subsequently show that this is due to antibody-dependent neutrophil extracellular trap (NET) formation in the middle ear, which, instead of clearing the infection, allows the bacteria to replicate. We further demonstrate the importance of these NETs as a potential therapeutic target through the transtympanic administration of a DNase, which effectively reduces the bacterial load in the middle ear. Taken together, these data provide novel insight into how pneumococci are able to replicate in the middle ear cavity and induce disease.
Monitoring the use of lipid-lowering medication among persons with newly diagnosed diabetes: a nationwide register-based study
Authors: Vehko Tuulikki , Sund Reijo , Arffman Martti , Manderbacka Kristiina , Ilanne-Parikka Pirjo , Keskimäki Ilmo 
Published: November 2013

ObjectivesTo develop a register-based monitoring system to provide information on the use of lipid-lowering medication among persons with diabetes in different patient groups and by socioeconomic position.DesignLongitudinal and register-based, before and after diabetes diagnosis.SettingFinnish population.ParticipantsA total of 121 053 persons aged 30–79 years with a new diagnosis of diabetes during 2000–2006. The annual cohorts were divided at the time of diabetes diagnosis by coronary heart disease (CHD) status.Primary and secondary outcome measuresLipid-lowering medication purchases after diabetes diagnosis and prior to the diagnosis.ResultsAccording to the health insurance reimbursement data the use of lipid-lowering medication advanced rapidly among people with diabetes in the early 2000s in Finland. Of the patients diagnosed with diabetes in 2000 only one-fourth used lipid-lowering medication in 6–12 months after their diagnosis. For those diagnosed in 2006, the utilization rate was 46%. Among those with a history of CHD the use of medication was markedly higher; 51–58% in 2000 and 77–79% in 2006. Taking into account the increasing trend and measuring the independent effect of the diagnosis of diabetes on lipid-lowering medication, setting the diagnosis increased the use by 10–50%. Despite increasing overall utilisation rates, socioeconomic difference in the use of lipid-lowering medication remained throughout the study period. In particular, the lowest income quintile differed from other income groups and in 2006 its use of lipid-lowering medication remained approximately 10% points lower compared with the overall level.ConclusionsThe lipid-lowering medication is being applied in an increasing population of new diabetes cases; however, modelling the independent effect of the diagnosis of diabetes on lipid-lowering medication shows that the diagnosis increased use, but did not abolish socioeconomic differences.
Targeting PARP-1 Allosteric Regulation Offers Therapeutic Potential against Cancer
Authors: Steffen Jamin D. , Tholey Renee M. , Langelier Marie-France , Planck Jamie L. , Schiewer Matthew J. , Lal Shruti , Bildzukewicz Nikolai A. , Yeo Charles J. , Knudsen Karen E. , Brody Jonathan R. , Pascal John M. 
Published: November 2013

AbstractPARP-1 is a nuclear protein that has important roles in maintenance of genomic integrity. During genotoxic stress, PARP-1 recruits to sites of DNA damage where PARP-1 domain architecture initiates catalytic activation and subsequent poly(ADP-ribose)–dependent DNA repair. PARP-1 inhibition is a promising new way to selectively target cancers harboring DNA repair deficiencies. However, current inhibitors target other PARPs, raising important questions about long-term off-target effects. Here, we propose a new strategy that targets PARP-1 allosteric regulation as a selective way of inhibiting PARP-1. We found that disruption of PARP-1 domain–domain contacts through mutagenesis held no cellular consequences on recruitment to DNA damage or a model system of transcriptional regulation, but prevented DNA-damage–dependent catalytic activation. Furthermore, PARP-1 mutant overexpression in a pancreatic cancer cell line (MIA PaCa-2) increased sensitivity to platinum-based anticancer agents. These results not only highlight the potential of a synergistic drug combination of allosteric PARP inhibitors with DNA-damaging agents in genomically unstable cancer cells (regardless of homologous recombination status), but also signify important applications of selective PARP-1 inhibition. Finally, the development of a high-throughput PARP-1 assay is described as a tool to promote discovery of novel PARP-1 selective inhibitors. Cancer Res; 74(1); 31–37. ©2013 AACR.
Complement Activation and Intraventricular Rituximab Distribution in Recurrent Central Nervous System Lymphoma
Authors: Kadoch Cigall , Li Jing , Wong Valerie S. , Chen Lingjing , Cha Soonmee , Munster Pamela , Lowell Clifford A. , Shuman Marc A. , Rubenstein James L. 
Published: November 2013

AbstractPurpose: To elucidate the mechanistic basis for efficacy of intrathecal rituximab. We evaluated complement activation as well as the pharmacokinetics of intraventricular rituximab in patients who participated in two phase 1 multicenter studies.Experimental Design: We evaluated complement activation as a candidate mediator of rituximab within the central nervous system (CNS). Complement C3 and C5b-9 were quantified by ELISA in serial cerebrospinal fluid (CSF) specimens after intraventricular rituximab administration. We determined rituximab concentration profiles in CSF and serum. A population three- compartment pharmacokinetic model was built to describe the disposition of rituximab following intraventricular administration. The model was derived from results of the first trial and validated with results of the second trial.Results: Complement C3 and C5b-9 were reproducibly activated in CSF after intraventricular rituximab. Ectopic expression of C3 mRNA and protein within CNS lymphoma lesions was localized to myeloid cells. Constitutive high C3 activation at baseline was associated with adverse prognosis. A pharmacokinetic model was built, which contains three distinct compartments, to describe the distribution of rituximab within the neuroaxis after intraventricular administration.Conclusions: We provide the first evidence of C3 activation within the neuroaxis with intraventricular immunotherapy and suggest that complement may contribute to immunotherapeutic responses of rituximab in CNS lymphoma. Penetration of rituximab into neural tissue is supported by this pharmacokinetic model and may contribute to efficacy. These findings have general implications for intraventricular immunotherapy. Our data highlight potential innovations to improve efficacy of intraventricular immunotherapy both via modulation of the innate immune response as well as innovations in drug delivery. Clin Cancer Res; 20(4); 1029–41. ©2013 AACR.
Radium Ra 223 Dichloride Injection: U.S. Food and Drug Administration Drug Approval Summary
Authors: Kluetz Paul G. , Pierce William , Maher V. Ellen , Zhang Hui , Tang Shenghui , Song Pengfei , Liu Qi , Haber Martin T. , Leutzinger Eldon E. , Al-Hakim Ali , Chen Wei , Palmby Todd , Alebachew Elleni , Sridhara Rajeshwari , Ibrahim Amna , Justice Robert , Pazdur Richard 
Published: November 2013

Abstract
On May 15, 2013, the U.S. Food and Drug Administration (FDA) approved radium Ra 223 dichloride (Ra-223; Xofigo injection; Bayer HealthCare Pharmaceuticals Inc.) for the treatment of patients with castration-resistant prostate cancer (CRPC), symptomatic bone metastases, and no known visceral metastatic disease. The FDA review was based on clinical trial BC1-06, which randomly allocated patients (2:1) to either Ra-223 plus best standard of care (BSoC) or placebo plus BSoC. The primary endpoint was overall survival (OS) with a key secondary endpoint of time to first symptomatic skeletal event (SSE). A statistically significant improvement in OS was demonstrated [HR, 0.70; 95% confidence interval, 0.55–0.88, P = 0.0019]. At the prespecified interim analysis, the median OS durations were 14.0 and 11.2 months in the Ra-223 and placebo arms, respectively. The improvement in OS was supported by a delay in time to first SSE favoring the Ra-223 arm. The most common (&gt;10%) adverse reactions in patients receiving Ra-223 were nausea, diarrhea, vomiting, and peripheral edema. The most common (&gt;10%) hematologic laboratory abnormalities were anemia, lymphocytopenia, leukopenia, thrombocytopenia, and neutropenia. Ra-223 is the first α-emitting radiotherapeutic and the first radiopharmaceutical to demonstrate an OS advantage in metastatic prostate cancer. Clin Cancer Res; 20(1); 9–14. ©2013 AACR.
Immune Impact Induced by PROSTVAC (PSA-TRICOM), a Therapeutic Vaccine for Prostate Cancer
Authors: Gulley James L. , Madan Ravi A. , Tsang Kwong Y. , Jochems Caroline , Marté Jennifer L. , Farsaci Benedetto , Tucker Jo A. , Hodge James W. , Liewehr David J. , Steinberg Seth M. , Heery Christopher R. , Schlom Jeffrey 
Published: November 2013

Abstract
PSA-TRICOM (PROSTVAC) is a novel vector-based vaccine designed to generate a robust immune response against prostate-specific antigen (PSA)-expressing tumor cells. The purpose of this report is to present an overview of both published studies and new data in the evaluation of immune responses to the PSA-TRICOM vaccine platform, currently in phase III testing. Of 104 patients tested for T-cell responses, 57% (59/104) demonstrated a ≥2-fold increase in PSA-specific T cells 4 weeks after vaccine (median 5-fold increase) compared with pre-vaccine, and 68% (19/28) of patients tested mounted post-vaccine immune responses to tumor-associated antigens not present in the vaccine (antigen spreading). The PSA-specific immune responses observed 28 days after vaccine (i.e., likely memory cells) are quantitatively similar to the levels of circulating T cells specific for influenza seen in the same patients. Measurements of systemic immune response to PSA may underestimate the true therapeutic immune response (as this does not account for cells that have trafficked to the tumor) and does not include antigen spreading. Furthermore, although the entire PSA gene is the vaccine, only one epitope of PSA is evaluated in the T-cell responses. Because this therapeutic vaccine is directed at generating a cellular/Th1 immune response (T-cell costimulatory molecules and use of a viral vector), it is not surprising that less than 0.6% of patients (2/349) tested have evidence of PSA antibody induction following vaccine. This suggests that post-vaccine PSA kinetics were not affected by PSA antibodies. An ongoing phase III study will evaluate the systemic immune responses and correlation with clinical outcomes. Cancer Immunol Res; 2(2); 133–41. ©2013 AACR.
National Trends in Heart Failure Hospitalization After Acute Myocardial Infarction for Medicare Beneficiaries
Authors: Chen Jersey , Hsieh Angela Fu-Chi , Dharmarajan Kumar , Masoudi Frederick A. , Krumholz Harlan M. 
Published: November 2013

Background—
Previous studies have reported conflicting findings regarding how the incidence of heart failure (HF) after acute myocardial infarction (AMI) has changed over time, and data on contemporary national trends are sparse.

Methods and Results—

Using a complete national sample of 2 789 943 AMI hospitalizations of Medicare fee-for-service beneficiaries from 1998 through 2010, we evaluated annual changes in the incidence of subsequent HF hospitalization and mortality using Poisson and survival analysis models. The number of patients hospitalized for HF within 1 year after AMI declined modestly from 16.1 per 100 person-years in 1998 to 14.2 per 100 person years in 2010 (
P
<0.001). After adjusting for demographic factors, a relative 14.6% decline for HF hospitalizations after AMI was observed over the study period (incidence risk ratio, 0.854; 95% confidence interval, 0.809–0.901). Unadjusted 1-year mortality following HF hospitalization after AMI was 44.4% in 1998, which decreased to 43.2% in 2004 to 2005, but then increased to 45.5% by 2010. After adjusting for demographic factors and clinical comorbidities, this represented a 2.4% relative annual decline (hazard ratio, 0.976; 95% confidence interval, 0.974–0.978) from 1998 to 2007, but a 5.1% relative annual increase from 2007 to 2010 (hazard ratio, 1.051; 95% confidence interval, 1.039–1.064).

Conclusions—
In a national sample of Medicare beneficiaries, HF hospitalization after AMI decreased from 1998 to 2010, which may indicate improvements in the management of AMI. In contrast, survival after HF following AMI remains poor, and has worsened from 2007 to 2010, demonstrating that challenges still remain for the treatment of this high-risk condition after AMI.
A new gall-inducing genus and species of Eriococcidae <br />(Hemiptera: Sternorrhyncha: Coccoidea) on Sapindaceae from Brazil
Authors: HODGSON CHRIS , ISAIAS ROSY M.S. , OLIVEIRA D. C. 
Published: November 2013

A new gall-inducing genus and species of felt scales (Hemiptera: Coccoidea: Eriococcidae) found on the leaves and twigs of Matayba guianensis (Sapindaceae) in Brazil is described: Bystracoccus Hodgson gen n. and B. mataybae Hodgson, Isaias & Oliveira sp. n. This is the first record of an eriococcid inducing leaf and stem galls on Sapindaceae and is only the second example of a member of the Eriococcidae to induce stem galls in which the insects diapause during the dry (winter) season. Only the adult female, second-instar female and crawler are known. The species overwinters as the first-instar nymph in pit galls on the twigs but spends the rest of the year associated with two-chambered galls on the leaves. It has recently become clear that South America has a rich felt-scale insect fauna many of which induce galls. It has proved very difficult to place this new genus in a family as it appears to fall between the Eriococcidae and Beesoniidae but is here placed in the eriococcids based on the similarity of the first-instar nymphs and the abundance of this family in the Neotropics. However, the dorsum of the abdomen of the mature adult female becomes heavily sclerotised, forming a round plug-like structure that completely fills the gall orifice. This structure shows remarkable morphological similarities to that of the beesoniid Danumococcus parashoreae Takagi & Hodgson found on Parashorea tomentella (Dipterocarpaceae) in Sabah, Malaysia, with which it is compared along with other eriococcid genera known from South America.
Skillful Wintertime North American Temperature Forecasts out to 4 Weeks Based on the State of ENSO and the MJO*
Authors: Johnson Nathaniel C. , Collins Dan C. , Feldstein Steven B. , L’Heureux Michelle L. , Riddle Emily E. 
Published: November 2013

Abstract
Previous work has shown that the combined influence of El Niño–Southern Oscillation (ENSO) and the Madden–Julian oscillation (MJO) significantly impacts the wintertime circulation over North America for lead times up to at least 4 weeks. These findings suggest that both the MJO and ENSO may prove beneficial for generating a seamless prediction link between short-range deterministic forecasts and longer-range seasonal forecasts. To test the feasibility of this link, wintertime (December–March) probabilistic 2-m temperature (T2m) forecasts over North America are generated solely on the basis of the linear trend and statistical relationships with the initial state of the MJO and ENSO. Overall, such forecasts exhibit substantial skill for some regions and some initial states of the MJO and ENSO out to a lead time of approximately 4 weeks. In addition, the primary ENSO T2m regions of influence are nearly orthogonal to those of the MJO, which suggests that the MJO and ENSO generally excite different patterns within the continuum of large-scale atmospheric teleconnections. The strong forecast skill scores for some regions and initial states confirm the promise that information from the MJO and ENSO may offer forecasts of opportunity in weeks 3 and 4, which extend beyond the current 2-week extended-range outlooks of the National Oceanic and Atmospheric Administration’s (NOAA) Climate Prediction Center (CPC), and an intraseasonal link to longer-range probabilistic forecasts.
Leg muscle power is enhanced by training in people with Parkinson’s disease: a randomized controlled trial
Authors: Paul Serene S , Canning Colleen G , Song Jooeun , Fung Victor SC , Sherrington Catherine 
Published: November 2013

Objective: To determine the effects of leg muscle power training in people with Parkinson’s disease. Design: Randomized controlled trial. Setting: University laboratory (outcome measures and experimental intervention), community (control intervention). Subjects: Community-dwelling people with Parkinson’s disease. Interventions: Leg muscle power training using pneumatic variable resistance equipment (experimental) was compared with low intensity sham exercise (control). Both groups exercised twice weekly for 12 weeks. Main measures: Primary outcomes were peak power of four leg muscle groups. Secondary outcomes were measures of muscle strength, mobility, balance and falls. Results: Exercise adherence was high in both groups. Leg muscle power was significantly better in the experimental group than the control group in all four primary outcome measures at 12 weeks after adjusting for baseline values: leg extensors (57.9 watts, 95% confidence interval (CI) 22.0–93.7, p = 0.002); knee flexors (29.6 watts, 95% CI 7.4–51.8, p = 0.01); hip flexors (68.1 watts, 95% CI 19.6–116.5, p = 0.007); and hip abductors (37.4 watts, 95% CI 19.9–54.9, p < 0.001). The experimental group performed significantly better on tests of leg muscle strength ( p < 0.001 to 0.07) and showed trends toward better performance in the Timed Up and Go ( p = 0.13) and choice stepping reaction time ( p = 0.11). There was a non-significant reduction in the rate of falls in the experimental group compared with the control group (incidence rate ratio 0.84, p = 0.76). Conclusions: This programme significantly improved muscle power in all trained muscle groups.
The effectiveness of virtual reality interventions in improving balance in adults with impaired balance compared with standard or no treatment: a systematic review and meta-analysis
Authors: Booth Vicky , Masud Tahir , Connell Louise , Bath-Hextall Fiona 
Published: November 2013

Objective: To evaluate whether virtual reality interventions, including interactive gaming systems, are effective at improving balance in adults with impaired balance. Design: Systematic review and meta-analysis of randomized control trials. Methods: Studies were identified from electronic databases (CENTRAL, MEDLINE, EMBASE, AMED, CINAHL, PyschINFO, PyschBITE, OTseeker, Ei Compendex, and Inspec) searched to November 2011, and repeated in November 2012. Two reviewers selected studies meeting inclusion criteria and quality of included studies assessed using a Joanna Briggs Institute appraisal tool. Data was pooled and a meta-analysis completed. The systematic review was reported following guidance of the PRISMA statement. Results: A total of 251 articles were screened. Eight randomized control trials were included. These studies presented the results of 239 participants, with various aetiologies, and used a variety of virtual reality systems. The number of falls was documented in only one included study. Meta-analysis was completed on data from the Berg Balance Scale, walking speed, 30 second sit-to-stand test, and Timed Up and Go Test, and favoured standard therapy when compared with standard plus virtual reality interventions. Conclusions: There was a notable inconsistency in the outcome measures, experimental, and control interventions used within the included studies. The pooled results of the studies showed no significant difference. Therefore this review cannot support nor refute the use of virtual reality interventions, rather than conventional physiotherapy, to improve balance in adults with impaired balance.
Angiotensin-converting enzyme gene insertion/deletion polymorphism studies in Asian Indian pregnant women biochemically identifies gestational diabetes mellitus
Authors: Khan Imran A , Jahan Parveen , Hasan Qurratulain , Rao Pragna 
Published: November 2013

Introduction: Gestational diabetes mellitus (GDM) is defined as glucose intolerance first recognized during pregnancy. Insertion/deletion (I/D) polymorphism of a 287 bp Alu repetitive sequence in intron 16 of the angiotensin-converting enzyme (ACE) gene has been widely investigated in Asian Indian populations with different ethnic origins. The present study examined possible association between I/D polymorphism of the ACE gene and GDM in Asian Indian pregnant women. Methods: A total of 200 pregnant women (100 GDM and 100 non-GDM) were recruited in this study and I/D polymorphism of a 287 bp Alu1 element inside intron 16 of the ACE gene was examined by polymerase chain reaction (PCR)-based gel electrophoresis. Result: The distribution of the variants like II, ID, and DD genotypes of ACE gene showed differences between normal GDM versus non-GDM subjects, and the frequency of the ID+ DD Vs II genotype was significant ( p=0.0002) in the GDM group. Conclusion: ACE gene polymorphism was associated with GDM in Asian Indian pregnant women.