bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multiple Sclerosis Therapeutic Pipeline: Opportunities and Challenges
Authors: Krieger Stephen 
Published: March 2011

AbstractThe year 2010 marked the beginning of the era of oral medications for the treatment of multiple sclerosis, with the approval of dalfampridine to improve walking and fingolimod as the first oral disease‐modifying agent. This review provides an overview of these and other emerging therapies, with an emphasis on the opportunities for new treatment paradigms they have the potential to offer, followed by a discussion of the challenges they will pose in the new era of multiple sclerosis management. Therapeutics in late‐stage development for MS include non‐selective immunosupressants, targeted immune‐modulators, and monoclonal antibodies. Oral agents including cladribine, teriflunomide, laquinimod, and dimethyl fumarate, as well as monoclonal antibodies alemtuzumab, daclizumab, and rituximab are considered. Potential side effects and adverse event monitoring, including opportunistic infections, emergent malignancies, and other systemic consequences of immunosuppression are discussed in a unified section. Challenges of optimally staging, sequencing, and combining treatments in the expanding multiple sclerosis armamentarium are discussed. This review emphasizes the multifactorial decision making that these new therapeutics will warrant in terms of patient selection and personalization/individualization of therapy, and the increasingly interdisciplinary approach that will be necessitated by the new generation of agents. Mt Sinai J Med 78:192–206, 2011 © 2011 Mount Sinai School of Medicine
Bed Rest in Pregnancy
Authors: Bigelow Catherine , Stone Joanne 
Published: March 2011

AbstractThe use of bed rest in medicine dates back to Hippocrates, who first recommended bed rest as a restorative measure for pain. With the formalization of prenatal care in the early 1900s, maternal bed rest became a standard of care, especially toward the end of pregnancy. Antepartum bed rest is a common obstetric management tool, with up to 95% of obstetricians utilizing maternal activity restriction in some way in their practice. Bed rest is prescribed for a variety of complications of pregnancy, from threatened abortion and multiple gestations to preeclampsia and preterm labor. Although the use of bed rest is pervasive, there is a paucity of data to support its use. Additionally, many well‐documented adverse physical, psychological, familial, societal, and financial effects have been discussed in the literature. There have been no complications of pregnancy for which the literature consistently demonstrates a benefit to antepartum bed rest. Given the well‐documented adverse effects of bed rest, disruption of social relationships, and financial implications of this intervention, there is a real need for scientific investigation to establish whether this is an appropriate therapeutic modality. Well‐designed randomized, controlled trials of bed rest versus normal activity for various complications of pregnancy are required to lay this debate to rest once and for all. Mt Sinai J Med 78:291–302, 2011. © 2011 Mount Sinai School of Medicine
Therapeutics for Multiple Sclerosis Symptoms
Authors: Ben‐Zacharia Aliza Bitton 
Published: March 2011

AbstractSymptoms management in multiple sclerosis is an integral part of its care. Accurate assessment and addressing the different symptoms provides increased quality of life among patients with multiple sclerosis. Multiple sclerosis symptoms may be identified as primary, secondary, or tertiary symptoms. Primary symptoms, such as weakness, sensory loss, and ataxia, are directly related to demyelination and axonal loss. Secondary symptoms, such as urinary tract infections as a result of urinary retention, are a result of the primary symptoms. Tertiary symptoms, such as reactive depression or social isolation, are a result of the social and psychological consequences of the disease. Common multiple sclerosis symptoms include fatigue and weakness; decreased balance, spasticity and gait problems; depression and cognitive issues; bladder, bowel, and sexual deficits; visual and sensory loss; and neuropathic pain. Less‐common symptoms include dysarthria and dysphagia, vertigo, and tremors. Rare symptoms in multiple sclerosis include seizures, hearing loss, and paralysis. Symptom management includes nonpharmacological methods, such as rehabilitation and psychosocial support, and pharmacological methods, ie, medications and surgical procedures. The keys to symptom management are awareness, knowledge, and coordination of care. Symptoms have to be recognized and management needs to be individualized. Multiple sclerosis therapeutics include nonpharmacological strategies that consist of lifestyle modifications, rehabilitation, social support, counseling, and pharmacological agents or surgical procedures. The goal is vigilant management to improve quality of life and promote realistic expectations and hope. Mt Sinai J Med 78:176–191, 2011. © 2011 Mount Sinai School of Medicine
Axonal Damage in Multiple Sclerosis
Authors: Haines Jeffery D. , Inglese Matilde , Casaccia Patrizia 
Published: March 2011

AbstractMultiple sclerosis is a debilitating disease of the central nervous system that has been characteristically classified as an immune‐mediated destruction of myelin, the protective coating on nerve fibers. Although the mechanisms responsible for the immune attack to central nervous system myelin have been the subject of intense investigation, more recent studies have focused on the neurodegenerative component, which is cause of clinical disability in young adults and appears to be only partially controlled by immunomodulatory therapies. Here, we review distinct, but not mutually exclusive, mechanisms of pathogenesis of axonal damage in multiple sclerosis patients that are either consequent to long‐term demyelination or independent from it. We propose that the complexity of axonal degeneration and the heterogeneity of the underlying pathogenetic mechanisms should be taken into consideration for the design of targeted therapeutic intervention. Mt Sinai J Med 78:231–243, 2011. © 2011 Mount Sinai School of Medicine
Progressive Multiple Sclerosis and Gray Matter Pathology: An MRI Perspective
Authors: Inglese Matilde , Oesingmann Niels , Casaccia Patrizia , Fleysher Lazar 
Published: March 2011

AbstractThe evidence suggesting a role of extensive cortical demyelization and atrophy in progressive multiple sclerosis is rapidly increasing. Although conventional magnetic resonance imaging has had a huge impact on multiple sclerosis by enabling an earlier diagnosis, and by providing surrogate markers for monitoring disease response to anti‐inflammatory/immunomodulatory treatments, it is limited by the low pathological specificity and the low sensitivity to both diffuse damage in normal‐appearing white matter and focal and diffuse damage in gray matter. Advanced magnetic resonance imaging techniques can partially overcome these limitations by providing markers more specific to the underlying pathologic substrates and more sensitive to the structural and functional “occult” brain tissue damage in patients with multiple sclerosis. This review describes brain and spinal cord imaging studies of multiple sclerosis with particular emphasis on gray matter imaging in both secondary progressive and primary progressive multiple sclerosis, discusses the clinical implications of gray matter damage, and outlines current magnetic resonance imaging developments at high and ultrahigh magnetic field strength. Mt Sinai J Med 78:258–267, 2011. © 2011 Mount Sinai School of Medicine
Computer‐Aided Diagnosis in Breast Magnetic Resonance Imaging
Authors: Muralidhar Gautam S. , Bovik Alan C. , Sampat Mehul P. , Whitman Gary J. , Haygood Tamara Miner , Stephens Tanya W. , Markey Mia K. 
Published: March 2011

AbstractIn this paper, we review the role played by breast magnetic resonance imaging in the detection and diagnosis of breast cancer. This is followed by a discussion of clinical decision support systems in medicine and their contributions in breast magnetic resonance imaging interpretation. We conclude by discussing the future of computer‐aided diagnosis in breast magnetic resonance imaging. Mt Sinai J Med 78:280–290, 2011. © 2011 Mount Sinai School of Medicine
Non‐verbal cues to osteoarthritic knee and/or hip pain in elders
Authors: Tsai Pao‐Feng , Kuo Yong‐Fang , Beck Cornelia , Richards Kathy , Means Kevin M. , Pate Barbara L. , Keefe Francis J. 
Published: March 2011

AbstractBehavioral cues are believed to be useful to identify pain among elders who may be experiencing pain but unable to express it. To examine this assumption, we recruited 192 elders who could verbally express pain to determine whether regression models combining behavioral cues (motor and gait patterns) predicted verbal pain reports. In the best model, age (p < .01) and subscales that measured guarding (p < .001) and joint flexion (p < .01) motor patterns were significant predictors of verbal pain reports. The receiver operating characteristic curve indicated that the best cutoff for predictive probability was 40–44%, with a fair to good C statistic of .78 (SD = .04). With a 40% cutoff, sensitivity and specificity were 71.6% and 71.0%, respectively. The investigators concluded that the final model could serve as a building block for the development of a tool using behavioral cues to identify elders' pain. © 2011 Wiley Periodicals, Inc. Res Nurs Health 34:218–227, 2011
A Systematic Review of Cognitive Stimulation Therapy for Older Adults with Mild to Moderate Dementia: An Occupational Therapy Perspective
Authors: Yuill Natasha , Hollis Vivien 
Published: March 2011

AbstractIn response to the need for effective non‐pharmacological approaches for individuals with mild to moderate dementia, cognitive stimulation therapy (CST) interventions aim to optimize cognitive function. The present literature review explored the effectiveness of CST and the congruence of this approach with occupational therapy. Twenty‐four databases and 13 “grey” sources were searched. Relevant papers were analysed using the McMaster Critical Literature Review Guidelines, the Modified Jadad Quality Scale and the Oxford Centre for Evidence‐based Medicine Levels of Evidence Scale. To establish the congruence of CST with occupational therapy, themes were identified using the International Classification of Functioning and professional values outlined by the Canadian Association of Occupational Therapists. Twelve studies demonstrated a trend towards delayed cognitive decline following CST. This intervention strategy is congruent with occupational therapy values and may provide a useful structural framework to build rehabilitation programmes for this population. Psychometric properties of the McMaster Guidelines have not yet been established, and there is no standardized way to extract quantitative data from this measure. There is a need for further research exploring outcomes of CST interventions within the context of everyday function in individuals experiencing cognitive decline. Copyright © 2011 John Wiley & Sons, Ltd.
Immune response to 2009 pandemic H1N1 influenza virus A monovalent vaccine in children with cancer
Authors: Yen Ting‐Yu , Jou Shiann‐Tarng , Yang Yung‐Li , Chang Hsiu‐Hao , Lu Meng‐Yao , Lin Dong‐Tsamn , Lin Kai‐Hsin , Huang Li‐Min , Chang Luan‐Yin 
Published: March 2011

AbstractPurposeThis study investigated the immune response to 2009 pandemic H1N1 influenza monovalent vaccine in children with cancer receiving chemotherapy.MethodsWe enrolled 25 pediatric patients. Ten patients younger than 10 years old received two vaccinations and the remaining 15 patients older than 10 years old received one. We checked hemagglutination‐inhibition (HAI) antibody titers in sera of patients before and 3–4 weeks after vaccination. Seroprotective titer was defined as HAI antibody titer ≥40 and seroresponse as ≥4‐fold increase in HAI antibody titers after vaccination.ResultsThe pre‐ and post‐vaccination seroprotective rates were 52% and 72% (P = 0.24). Sixteen (64%) patients were possibly exposed to 2009 pandemic H1N1 influenza previously, and there was significant association between possible exposure and pre‐vaccination seroprotective rate (P = 0.03). Post‐vaccination seroresponse rate was 32%, and seroresponse was greater in patients without pre‐vaccination seroprotective titer than those with pre‐vaccination seroprotective titer (50% vs. 15%, P = 0.07). Children with lymphocyte counts above 1,500/µl during vaccination period had better seroresponse than those with lymphocyte counts below 1,500/µl (P = 0.008). Post‐vaccination geometric mean titer (GMT) significantly increased in patients younger than 10 years receiving two vaccinations (pre‐ and post‐vaccination GMT were 21.4 and 60.6, respectively; P = 0.025).ConclusionsMonovalent vaccine for the 2009 pandemic H1N1 influenza A was found to be partially immunogenic in children with cancer, as evidenced by 32% of seroresponse rate. Immune response can be improved with vaccinations administered to patients whose absolute lymphocyte counts returned to a level of 1,500/µl or higher. Pediatr Blood Cancer 2011; 57: 1154–1158. © 2011 Wiley Periodicals, Inc.
Area‐based differentials in childhood cancer incidence in Australia, 1996–2006
Authors: Youlden Danny R. , Baade Peter D. , Valery Patricia C. , Hassall Timothy E. , Ward Leisa J. , Green Adele C. , Aitken Joanne F. 
Published: March 2011

AbstractBackgroundInternational studies examining the association between the incidence of childhood cancer and characteristics of the area in which the patient lives have generally reported inconsistent patterns. Area‐based differentials in childhood cancer throughout Australia have not been previously published at a national level.ProcedurePopulation‐based information from the Australian Paediatric Cancer Registry was used to identify all children aged 0‐ to 14‐years old diagnosed with invasive cancer or intracranial and intraspinal tumors of benign or uncertain behavior between 1996 and 2006. Age‐standardized incidence rates per million children per year and the corresponding incidence rate ratios were calculated, categorized by remoteness of residence and an area‐based index of socioeconomic disadvantage. Results were also stratified by the most common types of childhood cancer.ResultsThere was a significant, decreasing gradient in the incidence of childhood cancer as remoteness of residence increased. Children living in remote or very remote areas were 21% less likely to be diagnosed with cancer compared to children in major cities, mainly due to differences in the incidence of leukemias and lymphomas. This differential was no longer significant when only non‐Indigenous children were considered. No clear relationship was found between incidence and socioeconomic status (SES) in contrast to similar earlier studies.ConclusionsThe findings by remoteness of residence are consistent with the lower incidence rates of cancer that are typically associated with Indigenous Australians. There is also a suggestion that the etiological factors associated with childhood leukemia and SES may have altered over time. Pediatr Blood Cancer 2012; 58: 390–394. © 2011 Wiley Periodicals, Inc.
Therapeutic consequences for misdiagnosis of Type 2N von Willebrand disease
Authors: Gupta Madhu , Lillicrap David , Stain Ann Marie , Friedman Kenneth D. , Carcao Manuel D. 
Published: March 2011

AbstractPatients presenting with a low FVIII:C and with normal VWF levels are usually presumed to have hemophilia (males) or be carriers for hemophilia (females). Some of these patients may instead have VWD:2N. Such patients if misdiagnosed are likely to suffer from insufficiently treated bleeds. We report 2 males and 1 female who presented with a low FVIII:C (1–21%) and minimally reduced/normal VWF and were assumed to have, or be a carrier for, hemophilia A. Eventually all were found to have VWD:2N. Prior to the correct diagnosis the males had been treated with rFVIII with poor responses and ultimately adverse clinical consequences. Pediatr Blood Cancer 2011; 57: 1081–1083. © 2011 Wiley‐Liss, Inc.
Fetal stress hormone changes during intrauterine transfusions
Authors: Adama van Scheltema P. N. , Pasman S. A. , Wolterbeek R. , Deprest J. A. , Oepkes D. , De Buck F. , Van de Velde M. , Vandenbussche F. P. H. A. 
Published: March 2011

AbstractObjectiveTo document fetal stress hormone and Doppler changes after intrauterine transfusions (IUTs) in either the intrahepatic portion of the umbilical vein (IHV) or the placental cord insertion (PCI).MethodPregnant women scheduled for IUT for fetal anemia (N = 25) were included prospectively. Cortisol, β‐endorphin and noradrenalin concentrations in fetal plasma and middle cerebral artery pulsatility index before and after transfusion were compared. Transfusions were performed through the (IHV), thus puncturing the fetus, or at the PCI.ResultsThere were no measurable differences between the transfusion sites.ConclusionIn anemic fetuses undergoing transfusion, Doppler changes and fetal stress hormone changes were unrelated to the site of needle insertion. Copyright © 2011 John Wiley & Sons, Ltd.
Hierarchical structure of phase‐separated segmented polyurethane elastomers and its effect on properties
Authors: Bagdi Kristóf , Molnár Kinga , Wacha András , Bóta Attila , Pukánszky Béla 
Published: March 2011

AbstractPolyurethanes were prepared from 4,4′‐methylenebis(phenyl isocyanate), 1,4‐butanediol and poly(1,4‐butanediol adipate) polyester polyol. The hydroxyl functional group ratio of polyol/total diol was kept constant at 0.4, while the ratio of the isocyanate and hydroxyl groups (NCO/OH ratio) changed between 0.90 and 1.15. The polymers were prepared by one‐step bulk polymerization in an internal mixer. They were characterized using a number of methods including Fourier transform infrared spectroscopy, wide‐ and small‐angle X‐ray scattering, differential scanning calorimetry, dynamic mechanical analysis, light transmittance and tensile testing. Changing the stoichiometry modifies the molecular weight in accordance with the laws of stepwise polymerization, and the relative concentration of end groups also changes at the same time. Competitive interactions among various groups including chain‐end functional groups lead to the formation of slightly ordered phases of sub‐nanometre size at both ends of the composition range. These structures assemble into larger units at the 10 nm level, which associate further to even larger entities of micrometre size causing scattering of light and a decreased transparency of the samples. The order of the primary units, together with the number and size of assemblies at both higher levels, decrease as the composition approaches equimolar stoichiometry. The amount of less ordered amorphous phase has a maximum in this range. The stiffness of the polymers is determined by the amount of this phase, while ultimate properties are influenced also by molecular weight and the number of physical crosslinks formed. Copyright © 2010 Society of Chemical Industry
Minimising iTRAQ ratio compression through understanding LC‐MS elution dependence and high‐resolution HILIC fractionation
Authors: Ow Saw Yen , Salim Malinda , Noirel Josselin , Evans Caroline , Wright Phillip. C. 
Published: March 2011

AbstractApplication of iTRAQ‐based workflows for protein profiling has become widespread. Concomitantly, the idiosyncratic limitations of iTRAQ, such as its tendency to underestimate quantifications, have been studied and recognised. This report shows that the influence of ratio compression and limiting transmission in iTRAQ MS/MS in high‐complexity mixtures (iTRAQ‐labelled lysates) can be partly alleviated using high‐resolution sample fractionation. Here, we also investigate in greater detail the dependency of iTRAQ quantification on the dynamics of online chromatography in low‐complexity mixtures (iTRAQ‐labelled standards). These findings will allow more efficient strategies to be designed for iTRAQ proteomics, alleviating iTRAQ underestimation and thus facilitating the detection of subtle abundance changes.
Improving taxonomy‐based protein fold recognition by using global and local features
Authors: Yang Jian‐Yi , Chen Xin 
Published: March 2011

AbstractFold recognition from amino acid sequences plays an important role in identifying protein structures and functions. The taxonomy‐based method, which classifies a query protein into one of the known folds, has been shown very promising for protein fold recognition. However, extracting a set of highly discriminative features from amino acid sequences remains a challenging problem. To address this problem, we developed a new taxonomy‐based protein fold recognition method called TAXFOLD. It extensively exploits the sequence evolution information from PSI‐BLAST profiles and the secondary structure information from PSIPRED profiles. A comprehensive set of 137 features is constructed, which allows for the depiction of both global and local characteristics of PSI‐BLAST and PSIPRED profiles. We tested TAXFOLD on four datasets and compared it with several major existing taxonomic methods for fold recognition. Its recognition accuracies range from 79.6 to 90% for 27, 95, and 194 folds, achieving an average 6.9% improvement over the best available taxonomic method. Further test on the Lindahl benchmark dataset shows that TAXFOLD is comparable with the best conventional template‐based threading method at the SCOP fold level. These experimental results demonstrate that the proposed set of features is highly beneficial to protein fold recognition. Proteins 2011. © 2011 Wiley‐Liss, Inc.
Crystal structure of sulfolobus tokodaii sua5 complexed with L‐threonine and AMPPNP
Authors: Kuratani Mitsuo , Kasai Takuma , Akasaka Ryogo , Higashijima Kyoko , Terada Takaho , Kigawa Takanori , Shinkai Akeo , Bessho Yoshitaka , Yokoyama Shigeyuki 
Published: March 2011

AbstractThe hypermodified nucleoside N6‐threonylcarbamoyladenosine resides at position 37 of tRNA molecules bearing U at position 36 and maintains translational fidelity in the three kingdoms of life. The N6‐threonylcarbamoyl moiety is composed of L‐threonine and bicarbonate, and its synthesis was genetically shown to require YrdC/Sua5. YrdC/Sua5 binds to tRNA and ATP. In this study, we analyzed the L‐threonine‐binding mode of Sua5 from the archaeon Sulfolobus tokodaii. Isothermal titration calorimetry measurements revealed that S. tokodaii Sua5 binds L‐threonine more strongly than L‐serine and glycine. The Kd values of Sua5 for L‐threonine and L‐serine are 9.3 μM and 2.6 mM, respectively. We determined the crystal structure of S. tokodaii Sua5, complexed with AMPPNP and L‐threonine, at 1.8 Å resolution. The L‐threonine is bound next to AMPPNP in the same pocket of the N‐terminal domain. Thr118 and two water molecules form hydrogen bonds with AMPPNP in a unique manner for adenine‐specific recognition. The carboxyl group and the side‐chain hydroxyl and methyl groups of L‐threonine are buried deep in the pocket, whereas the amino group faces AMPPNP. The L‐threonine is located in a suitable position to react together with ATP for the synthesis of N6‐threonylcarbamoyladenosine. Proteins 2011. © 2011 Wiley‐Liss, Inc.