bluuebunny/crossref_metadata_2025_split huggingface dataset:
Responder analysis of a randomized comparison of the 13.3 mg/24 h and 9.5 mg/24 h rivastigmine patch
Authors: Molinuevo José L , Frölich Lutz , Grossberg George T , Galvin James E , Cummings Jeffrey L , Krahnke Tillmann , Strohmaier Christine 
Published: January 2015

Abstract
Introduction
OPtimizing Transdermal Exelon In Mild-to-moderate Alzheimer’s disease (OPTIMA) was a randomized, double-blind comparison of 13.3 mg/24 h versus 9.5 mg/24 h rivastigmine patch in patients with mild-to-moderate Alzheimer’s disease who declined despite open-label treatment with 9.5 mg/24 h patch. Over 48 weeks of double-blind treatment, high-dose patch produced greater functional and cognitive benefits compared with 9.5 mg/24 h patch.

Methods
Using OPTIMA data, a post-hoc responder analysis was performed to firstly, compare the proportion of patients demonstrating improvement or absence of decline with 13.3 mg/24 h versus 9.5 mg/24 h patch; and secondly, identify predictors of improvement or absence of decline. ‘Improvers’ were patients who improved on the Alzheimer’s Disease Assessment Scale–cognitive subscale (ADAS-cog) by ≥4 points from baseline, and did not decline on the instrumental domain of the Alzheimer’s Disease Cooperative Study–Activities of Daily Living scale (ADCS-IADL). ‘Non-decliners’ were patients who did not decline on either scale.

Results
Overall, 265 patients randomized to 13.3 mg/24 h and 271 to 9.5 mg/24 h patch met the criteria for inclusion in the intention-to-treat population and were included in the analyses. Significantly more patients were ‘improvers’ with 13.3 mg/24 h compared with 9.5 mg/24 h patch at Weeks 24 (44 (16.6%) versus 19 (7.0%); P < 0.001) and 48 (21 (7.9%) versus 10 (3.7%); P = 0.023). A significantly greater proportion of patients were ‘non-decliners’ with 13.3 mg/24 h compared with 9.5 mg/24 h patch at Week 24 (71 (26.8%) versus 44 (16.2%); P = 0.002). At Week 48, there was a trend in favor of 13.3 mg/24 h patch. Functional and cognitive assessment scores at double-blind baseline did not consistently predict effects at Weeks 24 or 48.

Conclusion
More patients with mild-to-moderate Alzheimer’s disease who are titrated to 13.3 mg/24 h rivastigmine patch at time of decline are ‘improvers’ or ‘non-decliners’ i.e. show responses on cognition and activities of daily living compared with patients remaining on 9.5 mg/24 h patch.

Trial registration
Clinicaltrials.gov identifier: NCT00506415; registered July 20, 2007.
Highly efficient gene knockout by injection of TALEN mRNAs into oocytes and host transfer in Xenopus laevis
Authors: Nakajima Keisuke , Yaoita Yoshio 
Published: January 2015

ABSTRACT
Zinc-finger nucleases, transcription activator-like effector nucleases (TALENs) and the CRISPR/Cas (clustered regularly interspaced short palindromic repeats/CRISPR-associated proteins) system are potentially powerful tools for producing tailor-made knockout animals. However, their mutagenic activity is not high enough to induce mutations at all loci of a target gene throughout an entire tadpole. In this study, we present a highly efficient method for introducing gene modifications at almost all target sequences in randomly selected embryos. The gene modification activity of TALEN is enhanced by adopting the host-transfer technique. In our method, the efficiency is further improved by injecting TALEN mRNAs fused to the 3′UTR of the Xenopus DEADSouth gene into oocytes, which are then transferred into a host female frog, where they are ovulated and fertilized. The addition of the 3′UTR of the DEADSouth gene promotes mRNA translation in the oocytes and increases the expression of TALEN proteins to near-maximal levels three hours post fertilization (hpf). In contrast, TALEN mRNAs without this 3′UTR are translated infrequently in oocytes. Our data suggest that genomic DNA is more sensitive to TALEN proteins from fertilization to the midblastula (MBT) stage. Our method works by increasing the levels of TALEN proteins during the pre-MBT stages.
A proteomic study of mitotic phase-specific interactors of EB1 reveals a role for SXIP-mediated protein interactions in anaphase onset
Authors: Tamura Naoka , Simon Judith E. , Nayak Arnab , Shenoy Rajesh , Hiroi Noriko , Boilot Viviane , Funahashi Akira , Draviam Viji M. 
Published: January 2015

ABSTRACT
Microtubules execute diverse mitotic events that are spatially and temporally separated; the underlying regulation is poorly understood. By combining drug treatments, large-scale immunoprecipitation and mass spectrometry, we report the first comprehensive map of mitotic phase-specific protein interactions of the microtubule-end binding protein, EB1. EB1 interacts with some, but not all, of its partners throughout mitosis. We show that the interaction of EB1 with Astrin-SKAP complex, a key regulator of chromosome segregation, is enhanced during prometaphase, compared to anaphase. We find that EB1 and EB3, another EB family member, can interact directly with SKAP, in an SXIP-motif dependent manner. Using an SXIP defective mutant that cannot interact with EB, we uncover two distinct pools of SKAP at spindle microtubules and kinetochores. We demonstrate the importance of SKAP's SXIP-motif in controlling microtubule growth rates and anaphase onset, without grossly disrupting spindle function. Thus, we provide the first comprehensive map of temporal changes in EB1 interactors during mitosis and highlight the importance of EB protein interactions in ensuring normal mitosis.
Tyrosine motifs are required for prestin basolateral membrane targeting
Authors: Zhang Yifan , Moeini-Naghani Iman , Bai JunPing , Santos-Sacchi Joseph , Navaratnam Dhasakumar S. 
Published: January 2015

ABSTRACT
Prestin is targeted to the lateral wall of outer hair cells (OHCs) where its electromotility is critical for cochlear amplification. Using MDCK cells as a model system for polarized epithelial sorting, we demonstrate that prestin uses tyrosine residues, in a YXXΦ motif, to target the basolateral surface. Both Y520 and Y667 are important for basolateral targeting of prestin. Mutation of these residues to glutamine or alanine resulted in retention within the Golgi and delayed egress from the Golgi in Y667Q. Basolateral targeting is restored upon mutation to phenylalanine suggesting the importance of a phenol ring in the tyrosine side chain. We also demonstrate that prestin targeting to the basolateral surface is dependent on AP1B (μ1B), and that prestin uses transferrin containing early endosomes in its passage from the Golgi to the basolateral plasma membrane. The presence of AP1B (μ1B) in OHCs, and parallels between prestin targeting to the basolateral surface of OHCs and polarized epithelial cells suggest that outer hair cells resemble polarized epithelia rather than neurons in this important phenotypic measure.
TACC3–ch-TOG track the growing tips of microtubules independently of clathrin and Aurora-A phosphorylation
Authors: Gutiérrez-Caballero Cristina , Burgess Selena G. , Bayliss Richard , Royle Stephen J. 
Published: January 2015

ABSTRACT
The interaction between TACC3 (transforming acidic coiled coil protein 3) and the microtubule polymerase ch-TOG (colonic, hepatic tumor overexpressed gene) is evolutionarily conserved. Loading of TACC3–ch-TOG onto mitotic spindle microtubules requires the phosphorylation of TACC3 by Aurora-A kinase and the subsequent interaction of TACC3 with clathrin to form a microtubule-binding surface. Recent work indicates that TACC3 can track the plus-ends of microtubules and modulate microtubule dynamics in non-dividing cells via its interaction with ch-TOG. Whether there is a pool of TACC3–ch-TOG that is independent of clathrin in human cells, and what is the function of this pool, are open questions. Here, we describe the molecular interaction between TACC3 and ch-TOG that permits TACC3 recruitment to the plus-ends of microtubules. This TACC3–ch-TOG pool is independent of EB1, EB3, Aurora-A phosphorylation and binding to clathrin. We also describe the distinct combinatorial subcellular pools of TACC3, ch-TOG and clathrin. TACC3 is often described as a centrosomal protein, but we show that there is no significant population of TACC3 at centrosomes. The delineation of distinct protein pools reveals a simplified view of how these proteins are organized and controlled by post-translational modification.
Clinical Sensitivity and Specificity of Meconium Fatty Acid Ethyl Ester, Ethyl Glucuronide, and Ethyl Sulfate for Detecting Maternal Drinking during Pregnancy
Authors: Himes Sarah K , Dukes Kimberly A , Tripp Tara , Petersen Julie M , Raffo Cheri , Burd Larry , Odendaal Hein , Elliott Amy J , Hereld Dale , Signore Caroline , Willinger Marian ,   for the Prenatal Alcohol in SIDS and Stillbirth (PASS) Network, Huestis Marilyn A 
Published: January 2015

Abstract

BACKGROUND
We investigated agreement between self-reported prenatal alcohol exposure (PAE) and objective meconium alcohol markers to determine the optimal meconium marker and threshold for identifying PAE.

METHODS
Meconium fatty acid ethyl esters (FAEE), ethyl glucuronide (EtG), and ethyl sulfate (EtS) were quantified by LC-MS/MS in 0.1 g meconium from infants of Safe Passage Study participants. Detailed PAE information was collected from women with a validated timeline follow-back interview. Because meconium formation begins during weeks 12–20, maternal self-reported drinking at or beyond 19 weeks was our exposure variable.

RESULTS
Of 107 women, 33 reported no alcohol consumption in pregnancy, 16 stopped drinking by week 19, and 58 drank beyond 19 weeks (including 45 third-trimester drinkers). There was moderate to substantial agreement between self-reported PAE at ≥19 weeks and meconium EtG ≥30 ng/g (κ = 0.57, 95% CI 0.41–0.73). This biomarker and associated cutoff was superior to a 7 FAEE sum ≥2 nmol/g and all other individual and combination marker cutoffs. With meconium EtG ≥30 ng/g as the gold standard condition and maternal self-report at ≥19 weeks' gestation as the test condition, 82% clinical sensitivity (95% CI 71.6–92.0) and 75% specificity (95% CI 63.2–86.8) were observed. A significant dose–concentration relationship between self-reported drinks per drinking day and meconium EtG ≥30 ng/g also was observed (all P &lt; 0.01).

CONCLUSIONS
Maternal alcohol consumption at ≥19 weeks was better represented by meconium EtG ≥30 ng/g than currently used FAEE cutoffs.
Free radical gelling reactions of lignosulfonates
Authors: Myrvold Bernt O. 
Published: January 2015

AbstractEleven different lignosulfonates (LS) and nine different free radical initiators have been tested in different concentrations to study the possibility of forming LS gels. It was found that the initiator must have a potential high enough for oxidizing the phenolic groups but not so high that would lead to a complete destruction of the LS. The chemical changes of the LS with different oxidants were observed in tests with low concentration of LS. The course of the reaction depends strongly on the type of oxidants that are able to gel the LS.
Telehealth Monitoring of Patients in the Community
Authors: Sparks Ross , Celler Branko , Okugami Chris , Jayasena Rajiv , Varnfield Marlien 
Published: January 2015

AbstractThis article outlines a decision support system that seeks to help community nurses monitor the well-being of their chronically ill patients. It is designed for nurses to stay in contact with their patients without spending unnecessary time on less productive aspects of community nursing, such as avoidable driving to and from patients’ houses and taking measurements of vital signs to assess their health condition. It therefore allows the nurse to spend more time on managing the factors that could lead to a healthier patient. The decision support system is developed for two levels of mathematical capability. Nurses with a statistical background are provided with in-depth information allowing them to detect changes in mean, mean square error (and hence variation), and correlations using a variation on dynamic principle components. Less mathematically inclined nurses are offered information about trends, change points, and a simpler multivariate view of a patient’s well-being involving parallel coordinate plots.
Effect of Optical Amplifiers on the Performance of SCM Radio over Fiber Systems
Authors: Sharma Sakshi , Bhatia Kamaljeet Singh , Kaur Harsimrat 
Published: January 2015

AbstractA bidirectional subcarrier multiplexing (SCM)-radio-over-fiber(RoF) network is proposed. In this paper, SCM RoFlink is analyzed with and without optical amplifier. The response of the system is studied for semiconductor optical amplifier (SOA), erbium-doped fiber amplifier (EDFA) and Raman amplifier. The results for the same are compared and then the appropriate amplifier is selected and the required gain for the optimal performance of the system is reported.
Phylogeny and systematics of the Crocidura suaveolens species group: corroboration and controversy between nuclear and mitochondrial DNA markers / Phylogénie et systématique du groupe d'espèces Crocidura suaveolens: coordination et contradiction des marqueurs nucléaire et mitochondriaux de l'ADN
Authors: Bannikova Anna A. , Lebedev Vladimir S. , Kramerov Dmitri A. , Zaitsev Mikhail V. 
Published: January 2015

AbstractDespite obvious advances in systematic research on Palaearctic white-toothed shrews ( Crocidura ), phylogenetic relationships and species diagnosis of 40-chromosome species ( suaveolens sp. group) remain poorly understood. Phylogenetic relationships of these shrews were analyzed on the basis of two independent molecular markers: interspersed repeat PCR fingerprints (inter-SINE-PCR) and complete (1140 bp) or partial (∼400 bp) sequences of the mtDNA cyt b gene. According to these data, C. suaveolens from Western Europe (Italy) appeared distinct from samples of C. suaveolens from Eastern Europe and Mongolia, as well as a Siberian sample. mtDNA introgression of Eastern European C. suaveolens with C. gueldenstaedtii in their contact zone in the Tuapse region was revealed. Hybrydization between C. gueldenstaedtii and C. suaveolens resulted in the formation of a population, nuclear DNA and morphological characteristics typical for C. gueldenstaedtii , while the mitochondrial genome is assimilated from C. suaveolens . The population of the Talysh region of the Caucasus ( C. caspica ) represents a separate entity that is clearly distinguished from the populations of Georgia and Tuapse ( C. gueldenstaedtii ) and C. suaveolens . Therefore, the position of C. caspica as a full species is supported. The present analysis of both inter-SINE-PCR and cyt b sequence data revealed two major clades in Palaearctic 40-chromosome Crocidura . The eastern clade is formed by true C. suaveolens/C. sibirica , together with C. caspica , and the western clade is formed by Western European C. suaveolens , which should be treated as a distinct species, C. mimula and the closely related C. gueldenstaedtii.
Limited Efficacy of α-Conopeptides, Vc1.1 and RgIA, To Inhibit Sensory Neuron CaVCurrent
Authors: Wright Andrew B. , Norimatsu Yohei , McIntosh J. Michael , Elmslie Keith S. 
Published: January 2015

AbstractChronic pain is very difficult to treat. Thus, novel analgesics are a critical area of research. Strong preclinical evidence supports the analgesic effects of α-conopeptides, Vc1.1 and RgIA, which block α9α10 nicotinic acetylcholine receptors (nAChRs). However, the analgesic mechanism is controversial. Some evidence supports the block of α9α10 nAChRs as an analgesic mechanism, while other evidence supports the inhibition of N-type CaV(CaV2.2) current via activation of GABABreceptors. Here, we reassess the effect of Vc1.1 and RgIA on CaVcurrent in rat sensory neurons. Unlike the previous findings, we found highly variable effects among individual sensory neurons, but on average only minimal inhibition induced by Vc1.1, and no significant effect on the current by RgIA. We also investigated the potential involvement of GABABreceptors in the Vc1.1-induced inhibition, and found no correlation between the size of CaVcurrent inhibition induced by baclofen (GABABagonist) versus that induced by Vc1.1. Thus, GABABreceptors are unlikely to mediate the Vc1.1-induced CaVcurrent inhibition. Based on the present findings, CaVcurrent inhibition in dorsal root ganglia is unlikely to be the predominant mechanism by which either Vc1.1 or RgIA induce analgesia.
Three-dimensional echocardiography of congenital abnormalities of the left atrioventricular valve
Authors: Rice Kathryn , Simpson John 
Published: January 2015

Abstract
Congenital abnormalities of the left atrioventricular (AV) valve are a significant diagnostic challenge. Traditionally, reliance has been placed on two-dimensional echocardiographic (2DE) imaging to guide recognition of the specific morphological features. Real-time 3DE can provide unique views of the left AV valve with the potential to improve understanding of valve morphology and function to facilitate surgical planning. This review illustrates the features of congenital abnormalities of the left AV valve assessed by 3DE. The similarities and differences in morphology between different lesions are described, both with respect to the valve itself and supporting chordal apparatus. The potential advantages as well as limitations of this technique in clinical practice are outlined.
Murine binder of sperm protein homolog 1: a new player in HDL-induced capacitation
Authors: Plante Geneviève , Manjunath Puttaswamy 
Published: January 2015

Binder of sperm (BSP) proteins are ubiquitous among mammals and are exclusively expressed in male genital tract. The main function associated with BSP proteins is their ability to promote sperm capacitation. In mice, two proteins (BSP protein homolog 1 (BSPH1) and BSPH2) have been studied. Using recombinant strategies, BSPH1 was found to bind to epididymal sperm membranes and promote sperm capacitationin vitro. The goal of this study was to evaluate the role of native murine BSPH1 protein in sperm capacitation induced by BSA and HDLs. The effect of antibodies, antigen-binding fragments (Fabs), and F(ab′)2specific for murine BSPH1 on BSA- and HDL-induced capacitation was tested. Results indicate that BSPH1 has no direct role in BSA-induced capacitation. However, antibodies, Fabs, and F(ab′)2could block capacitation induced by HDLs and could inhibit the HDL-induced increase in tyrosine phosphorylation, suggesting a specific interaction between HDLs and BSPH1. Results indicate that murine BSPH1 proteins in mice could be a new important piece of the puzzle in sperm capacitation induced by HDLs. As murine BSPH1 is orthologous to human BSPH1, this study could also lead to new insights into the functions and the importance of the human protein in male fertility.Free French abstractA French translation of this abstract is freely available athttp://www.reproduction-online.org/content/149/4/367/suppl/DC1.
The DNA Damage Response and Checkpoint Adaptation in Saccharomyces cerevisiae: Distinct Roles for the Replication Protein A2 (Rfa2) N-Terminus
Authors: Ghospurkar Padmaja L , Wilson Timothy M , Severson Amber L , Klein Sarah J , Khaku Sakina K , Walther André P , Haring Stuart J 
Published: January 2015

Abstract
In response to DNA damage, two general but fundamental processes occur in the cell: (1) a DNA lesion is recognized and repaired, and (2) concomitantly, the cell halts the cell cycle to provide a window of opportunity for repair to occur. An essential factor for a proper DNA-damage response is the heterotrimeric protein complex Replication Protein A (RPA). Of particular interest is hyperphosphorylation of the 32-kDa subunit, called RPA2, on its serine/threonine-rich amino (N) terminus following DNA damage in human cells. The unstructured N-terminus is often referred to as the phosphorylation domain and is conserved among eukaryotic RPA2 subunits, including Rfa2 in Saccharomyces cerevisiae. An aspartic acid/alanine-scanning and genetic interaction approach was utilized to delineate the importance of this domain in budding yeast. It was determined that the Rfa2 N-terminus is important for a proper DNA-damage response in yeast, although its phosphorylation is not required. Subregions of the Rfa2 N-terminus important for the DNA-damage response were also identified. Finally, an Rfa2 N-terminal hyperphosphorylation-mimetic mutant behaves similarly to another Rfa1 mutant (rfa1-t11) with respect to genetic interactions, DNA-damage sensitivity, and checkpoint adaptation. Our data indicate that post-translational modification of the Rfa2 N-terminus is not required for cells to deal with “repairable” DNA damage; however, post-translational modification of this domain might influence whether cells proceed into M-phase in the continued presence of unrepaired DNA lesions as a “last-resort” mechanism for cell survival.
Geographic Clusters in Underimmunization and Vaccine Refusal
Authors: Lieu Tracy A. , Ray G. Thomas , Klein Nicola P. , Chung Cindy , Kulldorff Martin 
Published: January 2015

BACKGROUND AND OBJECTIVE:
Parental refusal and delay of childhood vaccines has increased in recent years and is believed to cluster in some communities. Such clusters could pose public health risks and barriers to achieving immunization quality benchmarks. Our aims were to (1) describe geographic clusters of underimmunization and vaccine refusal, (2) compare clusters of underimmunization with different vaccines, and (3) evaluate whether vaccine refusal clusters may pose barriers to achieving high immunization rates.

METHODS:
We analyzed electronic health records among children born between 2000 and 2011 with membership in Kaiser Permanente Northern California. The study population included 154 424 children in 13 counties with continuous membership from birth to 36 months of age. We used spatial scan statistics to identify clusters of underimmunization (having missed 1 or more vaccines by 36 months of age) and vaccine refusal (based on International Classification of Diseases, Ninth Revision, Clinical Modification codes).

RESULTS:
We identified 5 statistically significant clusters of underimmunization among children who turned 36 months old during 2010–2012. The underimmunization rate within clusters ranged from 18% to 23%, and the rate outside them was 11%. Children in the most statistically significant cluster had 1.58 (P &lt; .001) times the rate of underimmunization as others. Underimmunization with measles, mumps, rubella vaccine and varicella vaccines clustered in similar geographic areas. Vaccine refusal also clustered, with rates of 5.5% to 13.5% within clusters, compared with 2.6% outside them.

CONCLUSIONS:
Underimmunization and vaccine refusal cluster geographically. Spatial scan statistics may be a useful tool to identify locations with challenges to achieving high immunization rates, which deserve focused intervention.
First record of Stenochrus portoricensis Chamberlin, 1922 (Arachnida: Schizomida: Hubbardiidae) for caves in Brazil: evidence for a troglophile status of an exotic species
Authors: Gallão Jonas , Bichuette Maria , Giupponi Alessandro 
Published: January 2015

New records of Stenochrus portoricensis Chamberlin, 1922 are given, the first south-american record in caves and the first to Goiás state in the Cerrado phytogeographical domain. Records of nine specimens (all females) in isolated regions from surface environment and deep zones in the cave suggest the status of troglophile (facultative cave-dwelling organisms) to this species. All specimens were found in places well preserved, without anthropization, differently from the observed to other records of the species in Brazil. Finally, we reinforce the need of replications on inventory studies of subterranean fauna.