bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy of HLA‐matched platelet transfusions for patients with hypoproliferative thrombocytopenia: a systematic review
Authors: Pavenski Katerina , Rebulla Paolo , Duquesnoy Rene , Saw Chee Loong , Slichter Sherrill J. , Tanael Susano , Shehata Nadine ,   International Collaboration for Guideline Development, Implementation and Evaluation for Transfusion Therapies (ICTMG) Collaborators
Published: April 2013

BackgroundHLA‐matched platelets (PLTs) are widely used to transfuse patients but the effectiveness of HLA matching has not been well defined and the cost is approximately five times the cost of preparing the random‐donor PLTs. The objective of this systematic review was to determine whether HLA‐matched PLTs lead to a reduction in mortality; reduction in frequency or severity of hemorrhage; reduction in HLA alloimmunization, refractoriness, or PLT utilization; or improvement in PLT count increment in patients with hypoproliferative thrombocytopenia.Study Design and MethodsWe conducted a literature search of MEDLINE, Cochrane Controlled Register of Clinical Trials, EMBASE, and PubMed databases to April 2012.ResultsA total of 788 citations were reviewed and 30 reports were included in the analysis. Most studies did not include technologies currently in use for HLA typing or detection of HLA antibodies as 75% were conducted before the year 2000. None of the studies were adequately powered to detect an effect on mortality or hemorrhage. HLA‐matched PLTs did not reduce alloimmunization and refractoriness rates beyond that offered by leukoreduction, and utilization was not consistently improved. HLA‐matched PLTs led to better 1‐hour posttransfusion count increments and percentage of PLT recovery in refractory patients; however, the effect at 24 hours was inconsistent.ConclusionThe correlation of the PLT increment with other clinical outcomes and the effect of leukoreduction on HLA‐matched PLT transfusion could not be determined. Prospective studies utilizing current technology and examining clinical outcomes are necessary to demonstrate the effectiveness of HLA‐matched PLT transfusion.
Human Infections and Detection of Plasmodium knowlesi
Authors: Singh Balbir , Daneshvar Cyrus 
Published: April 2013

SUMMARY

Plasmodium knowlesi
is a malaria parasite that is found in nature in long-tailed and pig-tailed macaques. Naturally acquired human infections were thought to be extremely rare until a large focus of human infections was reported in 2004 in Sarawak, Malaysian Borneo. Human infections have since been described throughout Southeast Asia, and
P. knowlesi
is now recognized as the fifth species of
Plasmodium
causing malaria in humans. The molecular, entomological, and epidemiological data indicate that human infections with
P. knowlesi
are not newly emergent and that knowlesi malaria is primarily a zoonosis. Human infections were undiagnosed until molecular detection methods that could distinguish
P. knowlesi
from the morphologically similar human malaria parasite
P. malariae
became available.
P. knowlesi
infections cause a spectrum of disease and are potentially fatal, but if detected early enough, infections in humans are readily treatable. In this review on knowlesi malaria, we describe the early studies on
P. knowlesi
and focus on the epidemiology, diagnosis, clinical aspects, and treatment of knowlesi malaria. We also discuss the gaps in our knowledge and the challenges that lie ahead in studying the epidemiology and pathogenesis of knowlesi malaria and in the prevention and control of this zoonotic infection.
Microbiology and Treatment of Acute Apical Abscesses
Authors: Siqueira José F. , Rôças Isabela N. 
Published: April 2013

SUMMARY

Acute apical abscess is the most common form of dental abscess and is caused by infection of the root canal of the tooth. It is usually localized intraorally, but in some cases the apical abscess may spread and result in severe complications or even mortality. The reasons why dental root canal infections can become symptomatic and evolve to severe spreading and sometimes life-threatening abscesses remain elusive. Studies using culture and advanced molecular microbiology methods for microbial identification in apical abscesses have demonstrated a multispecies community conspicuously dominated by anaerobic bacteria. Species/phylotypes commonly found in these infections belong to the genera
Fusobacterium
,
Parvimonas
,
Prevotella
,
Porphyromonas
,
Dialister
,
Streptococcus
, and
Treponema
. Advances in DNA sequencing technologies and computational biology have substantially enhanced the knowledge of the microbiota associated with acute apical abscesses and shed some light on the etiopathogeny of this disease. Species richness and abundance and the resulting network of interactions among community members may affect the collective pathogenicity and contribute to the development of acute infections. Disease modifiers, including transient or permanent host-related factors, may also influence the development and severity of acute abscesses. This review focuses on the current evidence about the etiology and treatment of acute apical abscesses and how the process is influenced by host-related factors and proposes future directions in research, diagnosis, and therapeutic approaches to deal with this disease.
Complement Component 3C3 and C3a Receptor Are Required in Chitin-Dependent Allergic Sensitization to Aspergillus fumigatus but Dispensable in Chitin-Induced Innate Allergic Inflammation
Authors: Roy René M. , Paes Hugo C. , Nanjappa Som G. , Sorkness Ron , Gasper David , Sterkel Alana , Wüthrich Marcel , Klein Bruce S. 
Published: April 2013

ABSTRACTLevels of the anaphylatoxin C3a are increased in patients with asthma compared with those in nonasthmatics and increase further still during asthma exacerbations. However, the role of C3a during sensitization to allergen is poorly understood. Sensitization to fungal allergens, such asAspergillus fumigatus, is a strong risk factor for the development of asthma. Exposure to chitin, a structural polysaccharide of the fungal cell wall, induces innate allergic inflammation and may promote sensitization to fungal allergens. Here, we found that coincubation of chitin with serum or intratracheal administration of chitin in mice resulted in the generation of C3a. We established a model of chitin-dependent sensitization to solubleAspergillusantigens to test the contribution of complement to these events. C3−/−and C3aR−/−mice were protected from chitin-dependent sensitization toAspergillusand had reduced lung eosinophilia and type 2 cytokines and serum IgE. In contrast, complement-deficient mice were not protected against chitin-induced innate allergic inflammation. In sensitized mice, plasmacytoid dendritic cells from complement-deficient animals acquired a tolerogenic profile associated with enhanced regulatory T cell responses and suppressed Th2 and Th17 responses specific forAspergillus. Thus, chitin induces the generation of C3a in the lung, and chitin-dependent allergic sensitization toAspergillusrequires C3aR signaling, which suppresses regulatory dendritic cells and T cells and induces allergy-promoting T cells.IMPORTANCEAsthma is one of the fastest growing chronic illnesses worldwide. Chitin, a ubiquitous polymer in our environment and a key component in the cell wall of fungal spores and the exoskeletons of insects, parasites, and crustaceans, triggers innate allergic inflammation. However, there is little understanding of how chitin is initially recognized by mammals and how early recognition of chitin affects sensitization to environmental allergens and development of allergic asthma. The complement system is evolutionarily one of the oldest facets of the early or innate warning systems in mammals. We studied whether and how complement components influence the recognition of chitin and shape the downstream sensitization toward fungal allergens. We show here that complement recognition of chitin plays a critical role in shaping the behavior of dendritic cells, which in turn regulate the function of T cells that mediate allergic responses to fungi.
Powerful Genetic Resource for the Study of Methicillin-Resistant Staphylococcus aureus
Authors: Hammer Neal D. , Skaar Eric P. 
Published: April 2013

ABSTRACT

In “A Genetic resource for Rapid and Comprehensive Phenotype Screening of Nonessential
Staphylococcus aureus
Genes” (mBio 4(2):e00537-12, doi: 10.1128/mBio.00537-12, 2013), Fey et al. describe the creation and application of a defined transposon mutant library of methicillin-resistant
S. aureus
. This library is well organized and made accessible to the research community through an easily navigable central repository. The mutant library promises to be a significant resource for researchers seeking a greater understanding of this pathogen.
Comparison of handheld rebound tonometry with Goldmann applanation tonometry in children with glaucoma: a cohort study
Authors: Dahlmann-Noor Annegret Hella , Puertas Renata , Tabasa-Lim Shenille , El-Karmouty Ahmed , Kadhim Mustafa , Wride Nicholas Kloster , Lewis Amanda , Grosvenor Dawn , Rai Poornima , Papadopoulos Maria , Brookes John , Bunce Catey , Khaw Peng Tee 
Published: April 2013

ObjectiveTo test agreement of two methods to measure intraocular pressure (IOP): rebound tonometry (RBT) and gold standard Goldmann applanation tonometry (GAT) in children with glaucoma.DesignObservational prospective cohort study.SettingTertiary paediatric glaucoma clinic at a single centre.Participants102 individuals attending a paediatric glaucoma clinic, mean (SD) age 11.85 (3.17), of whom 53 were male.Primary and secondary outcome measuresIntraocular pressure, central corneal thickness, child preference for measurement method.ResultsLimits of agreement for intraobserver and interobserver were, respectively, (−2.71, 2.98) mm Hg and (−5.75, 5.97) mm Hg. RBT frequently gave higher readings than GAT and the magnitude of disagreement depend on the level of IOP being assessed. Differences of 10 mm Hg were not uncommon. RBT was the preferred method for 70% of children.ConclusionsThere is poor agreement between RBT and GAT in children with glaucoma. RBT frequently and significantly overestimates IOP. However, ‘normal’ RBT readings are likely to be accurate and may spare children an examination under anaesthesia (EUA). High RBT readings should prompt the practitioner to use another standard method of IOP measurement if possible, or consider the RBT measurement in the context of clinical findings before referring the child to a specialist clinic or considering EUA.
Seroprevalence of syphilis among HIV-infected individuals in Addis Ababa, Ethiopia: a hospital-based cross-sectional study
Authors: Eticha Begna Tulu , Sisay Zufan , Alemayehu Addisu , Shimelis Techalew 
Published: April 2013

ObjectiveTo determine the prevalence of syphilis and its risk factors among people with HIV at a hospital in Ethiopia.DesignA hospital-based cross-sectional study.SettingThis study was conducted at one of the largest public hospitals in Addis Ababa , Ethiopia.ParticipantsA consecutive 306 HIV-positive patients were recruited prospectively from January to March 2010. For comparative purposes, 224 HIV-negative consecutive attendees at the voluntary counselling and testing centre in the same period were also included. Participants under 15 years of age and treated for syphilis and with a CD4 T-cell count below 50 cells/mm3were excluded.Outcome measuresBlood samples and data on sociodemographic and risk factors for syphilis were collected. Sera were screened for syphilis using rapid plasma reagin (RPR) test, and those positives were retested usingTreponema pallidumhaemagglutination assay (TPHA) test.ResultsThe seroprevalence of syphilis among HIV-infected individuals was 9.8% compared with 1.3% among HIV-uninfected individuals, OR 8.01 (95% CI 2.4 to 26.6; p=0.001). A comparable rate of syphilis was found among men (11%) and women (8.9%) with HIV infection. Syphilis prevalence non-significantly increased with age, with the highest rate in 40–49 years of age (16.9%). Except a history of sexually transmitted infections, which was associated with syphilis OR 2.25 (95% CI 1.03 to 4.9; p=0.042), other risk factors did not raise the odds of infection.ConclusionsThe high prevalence of syphilis among people with HIV infection highlights the need to target this population to prevent the transmission of both infections. Screening all HIV-infected people for syphilis and managing those infected would have clinical and epidemiological importance.
Specificity and sensitivity of transcranial sonography of the substantia nigra in the diagnosis of Parkinson's disease: prospective cohort study in 196 patients
Authors: Bouwmans Angela E P , Vlaar Annemarie M M , Mess Werner H , Kessels Alfons , Weber Wim E J 
Published: April 2013

ObjectiveNumerous ultrasound studies have suggested that a typical enlarged area of echogenicity in the substantia nigra (SN+) can help diagnose idiopathic Parkinson's disease (IPD). Almost all these studies were retrospective and involved patients with well-established diagnoses and long-disease duration. In this study the diagnostic accuracy of transcranial sonography (TCS) of the substantia nigra in the patient with an undiagnosed parkinsonian syndrome of recent onset has been evaluated.DesignProspective cohort study for diagnostic accuracy.SettingNeurology outpatient clinics of two teaching hospitals in the Netherlands.Patients196 consecutive patients, who were referred to two neurology outpatient clinics for analysis of clinically unclear parkinsonism. Within 2 weeks of inclusion all patients also underwent a TCS and a123I-ioflupane Single Photon Emission CT (FP-CIT SPECT) scan of the brain (n=176).Outcome measuresAfter 2 years, patients were re-examined by two movement disorder specialist neurologists for a final clinical diagnosis, that served as a surrogate gold standard for our study.ResultsTemporal acoustic windows were insufficient in 45 of 241 patients (18.67%). The final clinical diagnosis was IPD in 102 (52.0%) patients. Twenty-four (12.3%) patients were diagnosed with atypical parkinsonisms (APS) of which 8 (4.0%) multisystem atrophy (MSA), 6 (3.1%) progressive supranuclear palsy (PSP), 6 (3.1%) Lewy body dementia and 4 (2%) corticobasal degeneration. Twenty-one (10.7%) patients had a diagnosis of vascular parkinsonism, 20 (10.2%) essential tremor, 7 (3.6%) drug-induced parkinsonism and 22 (11.2%) patients had no parkinsonism but an alternative diagnosis. The sensitivity of a SN+ for the diagnosis IPD was 0.40 (CI 0.30 to 0.50) and the specificity 0.61 (CI 0.52 to 0.70). Hereby the positive predictive value (PPV) was 0.53 and the negative predictive value (NPV) 0.48. The sensitivity and specificity of FP-CIT SPECT scans for diagnosing IPD was 0.88 (CI 0.1 to 0.95) and 0.68 (CI 0.58 to 0.76) with a PPV of 0.75 and an NPV of 0.84.ConclusionsThe diagnostic accuracy of TCS in early stage Parkinson's disease is not sufficient for routine clinical use.Clinicaltrials.gov identifierNCT0036819
The safety and efficacy of intracoronary nitrite infusion during acute myocardial infarction (NITRITE-AMI): study protocol of a randomised controlled trial
Authors: Jones D A , Andiapen M , Van-Eijl T J A , Webb A J , Antoniou S , Schilling R J , Ahluwalia A , Mathur A 
Published: April 2013

IntroductionAcute myocardial infarction (AMI) is a major cause of death and disability in the UK and worldwide. Presently, timely and effective reperfusion with primary percutaneous coronary intervention (PPCI) remains the most effective treatment strategy for limiting infarct size, preserving left ventricular ejection fraction (LVEF) and improving clinical outcomes. However, the process of reperfusion can itself induce cardiomyocyte death, known as myocardial reperfusion injury, for which there is currently no effective therapy. Extensive preclinical evidence exists to suggest that sodium nitrite (as a source of endogenous nitric oxide) is an effective therapeutic strategy for preventing myocardial reperfusion injury. The purpose of NITRITE-AMI is to test whether sodium nitrite reduces reperfusion injury and subsequent infarct size in patients undergoing PPCI for MI.Methods and designNITRITE-AMI is a double-blind, randomised, single-centre, placebo-controlled trial to determine whether intracoronary nitrite injection reduces infarct size in patients with myocardial infarction undergoing primary angioplasty. The study will enrol 80 patients presenting with ST-elevation myocardial infarction. Patients will be randomised to receive either a bolus of intracoronary sodium nitrite or placebo (sodium chloride) at the time of PPCI. The primary outcome is infarct size assessed by creatine kinase area under the curve (AUC) over 48 h. Secondary endpoints include troponin T AUC and infarct size, LV dimensions and myocardial salvage index assessed by cardiac MR (CMR), markers of platelet reactivity and inflammation, the safety and tolerability of intracoronary nitrite, and 1 year major adverse cardiac events.Ethics and disseminationThe study is approved by the local ethics committee (NRES Committee London West London: 11/LO/1500) and by the Medicines and Healthcare Products Regulatory Agency (MHRA) (EudraCT nr. 2010-022460-12). The results of the trial will be published according to the CONSORT statement and will be presented at conferences and reported in peer-reviewed journals.Trial registrationUnited Kingdom Clinical Research Network (Study ID 12117),http://clinicaltrials.gov(NCT01584453) and Current Controlled Trials (ISRCTN:38736987).
SO(10) GUT IN FOUR AND FIVE DIMENSIONS: A REVIEW
Authors: FUKUYAMA TAKESHI 
Published: April 2013

We review SO(10) grand unified theories (GUTs) in four and five dimensions (4D and 5D). The renormalizable minimal SO(10) SUSY GUT is the central theme of this paper. It is very predictive and makes it possible to construct all mass matrices including those of the Dirac and heavy right-handed Majorana neutrinos. Its predictions covers all ranges of particle phenomena. The explicit construction of the Higgs superpotential and the explicit display of a symmetry breaking pattern from GUT to the SM show that the naive desert from the SM to GUT in the minimal supersymmetric standard model (MSSM) is a too simplified concept and we have many definitely determined intermediate energy scales in general. This situation destroys the naive gauge coupling unification in the MSSM scheme. Also the precise measurements of neutrino oscillation data have revealed several small but manifest mismatches with our predictions. Also there are arguments that it is impossible to construct a GUT theory in 4D with a finite number of multiplets that leads to the MSSM with a residual R symmetry. If we try to solve all these pathologies comprehensively, it is very attractive for us to go into extra dimensions. Extra dimension may be either warped or flat. The fifth dimension, for simplicity, is compactified on the S1/(Z2) (warped) or on the S1/(Z2×Z′2) (flat) orbifold with two inequivalent branes at the orbifold fixed points. In the former warped case, intermediate energy scales are translated with the positions of Higgs fields in the bulk and the fundamental scheme of the MSSM is recovered. On the other hand, in the latter flat scenario, all matter and Higgs multiplets reside on the Pati–Salam (PS) brane where the PS symmetry is manifest. There the original renormalizability in Yukawa coupling is broken but its essential structures of mass matrices in minimal SO(10) GUT in 4D is promoted to the PS invariant action in 4D. In the gaugino mediation mechanism, the SO(10) gauge multiplet is transmitted to the PS brane through the gaugino mediation with bulk gauge multiplet. Further breaking of the PS gauge group to the SM group is realized by VEVs of the Higgs multiplets [Formula: see text]. We show that this model not only cures all pathologies in SO(10) GUT in 4D but also provides the consistent inflation scenario and dark matter candidate and leptogenesis. The gauge coupling unification is successfully realized after incorporating the threshold corrections of the Kaluza–Klein modes. Finally we add some comments on the impacts of the discovery of a Higgs-like particle by the Large Hadronic Collider at CERN (LHC) on SUSY GUTs.
Pharmaceutical use of gold from antiquity to the seventeenth century
Authors: Console Renzo 
Published: April 2013

Abstract

Following extensive bibliographical research, a chronological history of the pharmaceutical use of gold is outlined through four periods: antiquity, the Middle Ages, early modern times and the seventeenth century. At the time of its highest popularity as a medicine, gold was usually acquired and employed in the form of fine filings or thin leaves of standard size. The most complex and famous medicine containing gold was
Aurea Alexandrina
, created in the late Middle Ages and later copied into many books. A complete list of its ingredients in Latin and English is included in the present paper. As in
Aurea Alexandrina
, gold was very often accompanied in a formula by other precious components like silver, gems and pearls. In addition to being an important ingredient in many medicines, gold was also used for making surgical instruments and for coating pills that otherwise had a bad taste or smell. The medicinal use of gold, even when it was very fashionable, was not unanimously regarded as effective and many authors clearly expressed either enthusiasm or scepticism about this matter.
miR145 Targets the SOX9/ADAM17 Axis to Inhibit Tumor-Initiating Cells and IL-6–Mediated Paracrine Effects in Head and Neck Cancer
Authors: Yu Cheng-Chia , Tsai Lo-Lin , Wang Mong-Lien , Yu Chuan-Hang , Lo Wen-Liang , Chang Yun-Ching , Chiou Guang-Yuh , Chou Ming-Yung , Chiou Shih-Hwa 
Published: April 2013

Abstract
ALDH1+CD44+ cells are putative tumor-initiating cells (TIC) in head and neck squamous cell carcinomas (HNC). miR-145 regulates tumorigenicity in various cancers but the breadth of its mechanistic contributions and potential therapeutic applications are not completely known. Here, we report that ALDH1+CD44+-HNC cells express reduced levels of miR145. SPONGE-mediated inhibition of miR-145 (Spg-miR145) was sufficient to drive tumor-initiating characteristics in non-TICs/ALDH1−CD44-negative HNC cells. Mechanistic analyses identified SOX9 and ADAM17 as two novel miR145 targets relevant to this process. miR-145 expression repressed TICs in HNC in a manner associated with SOX9 interaction with the ADAM17 promoter, thereby activating ADAM17 expression. Notably, the SOX9/ADAM17 axis dominated the TIC-inducing activity of miR-145. Either miR-145 suppression or ADAM17 overexpression in non-TICs/ALDH1−CD44−-HNC cells increased expression and secretion of interleukin (IL)-6 and soluble-IL-6 receptor (sIL-6R). Conversely, conditioned medium from Spg-miR145–transfected non-TICs/ALDH1−CD44−-HNC cells was sufficient to confer tumor-initiating properties in non-TICs/ALDH1−CD44−-HNC and this effect could be abrogated by an IL-6–neutralizing antibody. We found that curcumin administration increased miR-145 promoter activity, thereby decreasing SOX9/ADAM17 expression and eliminating TICs in HNC cell populations. Delivery of lentivral-miR145 or orally administered curcumin blocked tumor progression in HNC-TICs in murine xenotransplant assays. Finally, immunohistochemical analyses of patient specimens confirmed that an miR-145low/SOX9high/ADAM17high phenotype correlated with poor survival. Collectively, our results show how miR-145 targets the SOX9/ADAM17 axis to regulate TIC properties in HNC, and how altering this pathway may partly explain the anticancer effects of curcumin. By inhibiting IL-6 and sIL-6R as downstream effector cytokines in this pathway, miR-145 seems to suppress a paracrine signaling pathway in the tumor microenvironment that is vital to maintain TICs in HNC. Cancer Res; 73(11); 3425–40. ©2013 AACR.