bluuebunny/crossref_metadata_2025_split huggingface dataset:
Management of acute ischaemic stroke in patients with dementia
Authors: Subic A. , Cermakova P. , Norrving B. , Winblad B. , von Euler M. , Kramberger M. G. , Eriksdotter M. , Garcia‐Ptacek S. 
Published: February 2017

AbstractAn estimated 10% of stroke patients have an underlying dementia. As a consequence, health professionals often face the challenge of managing patients with dementia presenting with an acute stroke. Patients with dementia are less likely to receive thrombolysis (0.56–10% vs. 1–16% thrombolysis rates in the general population), be admitted to a stroke unit or receive some types of care. Anticoagulation for secondary stroke prevention is sometimes withheld, despite dementia not being listed as an exclusion criterion in current guidelines. Studies in this population are scarce, and results have been contradictory. Three observational studies have examined intravenous thrombolysis for treatment of acute ischaemic stroke in patients with dementia. In the two largest matched case–control studies, there were no significant differences between patients with and without dementia in the risks of intracerebral haemorrhage or mortality. The risk of intracerebral haemorrhage ranged between 14% and 19% for patients with dementia. Studies of other interventions for stroke are lacking for this population. Patients with dementia are less likely to be discharged home compared with controls (19% vs. 41%) and more likely to be disabled (64% vs. 59%) or die during hospitalization (22% vs. 11%). The aim of this review was to summarize current knowledge about the management of ischaemic stroke in patients with pre‐existing dementia, including organizational aspects of stroke care, intravenous thrombolysis, access to stroke unit care and use of supportive treatment. Evidence to support anticoagulation for secondary prevention of stroke in patients with atrial fibrillation and antiplatelet therapy in nonembolic stroke will be discussed, as well as rehabilitation and how these factors influence patient outcomes. Finally, ethical issues, knowledge gaps and pathways for future research will be considered.
Efficacy and Safety of Gabapentin in Comparison to Solifenacin Succinate in Adult Overactive Bladder Treatment
Authors: CHUA Michael E. , SEE Manuel C. , ESMEŇA Ednalyn B. , BALINGIT Jaime C. , MORALES Marcelino L. 
Published: February 2017

ObjectiveTo evaluate the efficacy and safety of gabapentin in comparison to solifenacin succinate and placebo for the treatment of adult patients with overactive bladder (OAB).MethodA 12‐week, randomized, double‐blind, double dummy placebo‐controlled, clinical trial was conducted between October 2010 and August 2014 at a tertiary medical center. Eligible and consenting patients included were randomized into three treatment groups (placebo, gabapentin and solifenacin). After a 12‐week treatment period, an intention to treat analysis was applied to assess between group differences on the micturitions and urgency episodes per 24 h; which were evaluated by 3‐day micturition diary mean change from baseline to post treatment. Health related quality of life (HRQOL) domains were likewise assessed by OAB questionnaire (OAB‐q). Adverse event were monitored and summarized. Study results were analyzed at statistical significance of 0.05. (ClinicalTrials.gov ID NCT01486706)ResultA total of 94 participants were included for end‐study efficacy and safety analysis. Compared to placebo, gabapentin and solifenacin have statistically significant improvement in mean number of micturitions per 24 h (adjusted mean difference [AMD] −1.179, 95%CI −1.98, −0.38; P < 0.001; −1.706, 95%CI −2.52, −0.09; P < 0.001; respectively), and in mean number of urgency episodes per 24 h (AMD −0.903, 95%CI −1.44, −0.37; P < 0.001; −0.896, 95%CI −1.44, −0.35; P < 0.001). Gabapentin also demonstrated significant improvement over the solifenacin in the mean number of nocturia episodes/24 h (AMD −0.607, 95%CI −1.04, −0.18; P < 0.001). Adverse event related to gabapentin treatment was lesser than solifenacin, and comparable to placebo.ConclusionGabapentin treatment with acceptable safety profile, improves OAB symptoms and HRQOL domains.
T cell responses to peptides of Goodpasture autoantigen in patients with anti‐glomerular basement membrane disease
Authors: Hu Shui‐Yi , Jia Xiao‐Yu , Gu Qiu‐Hua , Yu Chong‐Yan , Cheng Xu‐Yang , Jin Qi‐Zhuang , Zhou Fu‐De , Cui Zhao , Zhao Ming‐Hui 
Published: February 2017

AbstractAimCell‐mediated autoimmunity, especially autoreactive T cells, is crucial in the initiation of anti‐glomerular membrane (GBM) disease. Epitopes for T cells on Goodpasture autoantigen are not fully defined. This study investigated T cell epitopes in anti‐GBM patients, aiming to identify the epitopes and their clinical significance.MethodsPeripheral blood mononuclear cells (PBMC) were collected from 13 patients with anti‐GBM disease. Twenty‐four overlapping linear peptides were synthesized covering the whole sequence of human α3(IV)NC1. PBMC response to each peptide was detected by proliferation assay. Their associations with clinical features were further analyzed.ResultsPeripheral blood mononuclear cells proliferative responses to linear peptides on α3(IV)NC1 could be detected in all patients. Five major epitopes were identified as stimulatory in over half of the patients: α3(IV)NC1127–148 (P14) (69.2%), α3(IV)NC1159–178 (77.8%), α3(IV)NC1179–198 (55.6%), α3(IV)NC1189–208 (P19) (75.0%) and α3(IV)NC1141–154 (57.1%). P14 and P19 were highly recognized in patients comparing with healthy controls (69.2% vs. 0.0%, P = 0.011; 75.0% vs. 0.0%, P = 0.021, respectively).ConclusionT cell proliferation to linear epitopes was detected in human anti‐GBM disease. α3127–148 was a mutual T and B cell epitope, implying its initial role in epitope spreading process.
Registration of serial maxillary models via the weighted rugae superimposition method
Authors: Abdi A. H. , Nouri M. 
Published: February 2017

ObjectivesWe introduce a weighted method for superimposition of serial digital maxillary models based on the variable stability of rugae points.Setting and sample populationPlaster maxillary models of 24 randomly selected 12‐year‐olds as well as their models at the age of 14 were obtained and scanned using a benchtop structured‐light 3D scanner.MethodsThe models were registered twice, once via the unweighted and again via the proposed weighted rugae superimposition method based on 12 rugae landmarks. For each superimposition, distances between the corresponding rugae points were measured and compared with reported displacements of rugae points in literature.ResultsThe unweighted superimposition produced no meaningful differences in terms of total displacements of registration landmarks, whereas the weighted method recognized the medial points of the third ruga as the most stable landmarks. Results of the weighted method also demonstrated statistically significant smaller changes for medial rugae points in almost every dimension compared to the lateral rugae points. These results comply with the growth patterns of maxilla and rugae point displacements reported in similar studies.ConclusionConsidering the variable stability of rugae points during growth, the weighted rugae superimposition method results in more promising registrations on serial models. This method prioritizes registration landmarks based on clinical criteria of choice and is suitable for analysis of other structures such as tooth movements.
A prevalence study of bifid mandibular canals using cone beam computed tomography
Authors: Allison J.R. , Carr A. 
Published: February 2017

AbstractAimThis study aims to assess the prevalence of bifid mandibular canals in a UK population using cone beam computed tomography.Materials and MethodsThis is a prevalence study of 140 patients (280 sides) referred to a dental hospital in the UK for extraction of a third molar. Canals were classified from cone beam computed tomography images using a novel classification.ResultsAt least one bifid canal was seen in 30.00% (n = 42/140) of patients (95% CI: 26.13–33.87%) and in 18.93% (n = 53/280) of sides (95% CI: 16.59–21.27%). The retromolar canal was the most common variant observed.ConclusionsThe bifid mandibular canal appears to be a common anatomical variant, of which clinicians should be aware. These variants are relevant to surgery in the retromolar region, dental extraction and implant placement, where damage has the potential to cause bleeding and sensory disturbance.
Enhanced metal tolerance correlates with heterotypic variation in SpMTL, a metallothionein‐like protein from the hyperaccumulator Sedum plumbizincicola
Authors: Peng Jia‐Shi , Ding Ge , Meng Shuan , Yi Hong‐Ying , Gong Ji‐Ming 
Published: February 2017

AbstractMechanistic insight into metal hyperaccumulation is largely restricted to Brassicaceae plants; therefore, it is of great importance to obtain corresponding knowledge from system outside the Brassicaceae. Here, we constructed and screened a cDNA library of the Cd/Zn hyperaccumulator Sedum plumbizincicola and identified a novel metallothionein‐like protein encoding gene SpMTL. SpMTL showed functional similarity to other known MT proteins and also to its orthologues from non‐hyperaccumulators. However, three additional cysteine residues were observed in SpMTL and appeared to be hyperaccumulator specific. Removal of these three residues significantly decreased its ability to tolerate Cd and the stoichiometry of Cd against SpMTL (molar ratio of Cd/SpMTL) to a level comparable to those of Cd/SaMTL and Cd/SeMTL in the corresponding non‐hyperaccumulating relatives. SpMTL expressed in S. plumbizincicola roots at a much higher level than those of its orthologues in the non‐hyperaccumulator roots. Interestingly, a positive correlation was observed between transcript levels of SpMTL in roots and Cd accumulation in leaves. Taking these results together, we propose that elevated transcript levels and heterotypic variation in protein sequences of SpMTL might contribute to the trait of Cd hyperaccumulation and hypertolerance in S. plumbizincicola.
Unexpected distribution patterns of Carduiceps feather lice (Phthiraptera: Ischnocera: Philopteridae) on sandpipers (Aves: Charadriiformes: Scolopacidae)
Authors: GUSTAFSSON DANIEL R. , OLSSON URBAN 
Published: February 2017

AbstractThe louse genus Carduiceps Clay & Meinertzhagen, 1939 is widely distributed on sandpipers and stints (Calidrinae). The current taxonomy includes three species on the Calidrinae (Carduiceps meinertzhageni, Carduiceps scalaris, Carduiceps zonarius) and four species on noncalidrine hosts. We estimated a phylogeny of four of the seven species of Carduiceps (the three mentioned above and Carduiceps fulvofasciatus) from 13 of the 29 hosts based on three mitochondrial loci, and evaluated the relative importance of flyway differentiation (same host species has different lice along different flyways) and flyway homogenization (different host species have the same lice along the same flyway). We found no evidence for either process. Instead, the present, morphology‐based, taxonomy of the genus corresponds exactly to the gene‐based phylogeny, with all four included species monophyletic. Carduiceps zonarius is found both to inhabit a wider range of hosts than wing lice of the genus Lunaceps occurring on the same group of birds, and to occur on Calidris sandpipers of all sizes, both of which are unexpected for a body louse. The previously proposed family Esthiopteridae is found to be monophyletic with good support. The concatenated dataset suggests that the pigeon louse genus Columbicola may be closely related to the auk and diver louse genus Craspedonirmus. These two genera share some morphological characters with Carduiceps, but no support was obtained for grouping these three genera together. Based on mitochondrial data alone, the relationships among genera within this proposed family cannot be properly assessed, but some previously suggested relationships within this proposed family are confirmed.
Beta-Propiolactone Inactivation of Coxsackievirus A16 Induces Structural Alteration and Surface Modification of Viral Capsids
Authors: Fan Chen , Ye Xiaohua , Ku Zhiqiang , Kong Liangliang , Liu Qingwei , Xu Cong , Cong Yao , Huang Zhong 
Published: February 2017

ABSTRACT
Beta-propiolactone (BPL) is an inactivating agent that is widely used in the vaccine industry. However, its effects on vaccine protein antigens and its mechanisms of action remain poorly understood. Here we present cryo-electron microscopy (cryo-EM) structures of BPL-treated coxsackievirus A16 (CVA16) mature virions and procapsids at resolutions of 3.9 Å and 6.5 Å, respectively. Notably, both particles were found to adopt an expanded conformation resembling the 135S-like uncoating intermediate, with characteristic features including an opened 2-fold channel, the externalization of the N terminus of VP1 capsid protein, and the absence of pocket factor. However, major neutralizing epitopes are very well preserved on these particles. Further biochemical analyses revealed that BPL treatment impairs the abilities of CVA16 particles to bind to the attachment receptor heparan sulfate and to a conformation-dependent monoclonal antibody in a BPL dose-dependent manner, indicating that BPL is able to modify surface-exposed amino acid residues. Taken together, our results demonstrate that BPL treatment may induce alteration of the overall structure and surface properties of a nonenveloped viral capsid, thus revealing a novel mode of action of BPL.

IMPORTANCE
Beta-propiolactone (BPL) is commonly used as an inactivating reagent to produce viral vaccines. It is recognized that BPL inactivates viral infectivity through modification of viral nucleic acids. However, its effect on viral proteins remains largely unknown. Here, we present high-resolution cryo-EM structures of BPL-treated coxsackievirus A16 (CVA16) mature virions and procapsids, which reveals an expanded overall conformation and characteristic features that are typical for the 135S-like uncoating intermediate. We further show that the BPL concentration affects the binding of inactivated CVA16 particles to their receptor/antibody. Thus, BPL treatment can alter the overall structure and surface properties of viral capsids, which may lead to antigenic and immunogenic variations. Our findings provide important information for future development of BPL-inactivated vaccines.
Neurovirulent Murine Coronavirus JHM.SD Uses Cellular Zinc Metalloproteases for Virus Entry and Cell-Cell Fusion
Authors: Phillips Judith M. , Gallagher Tom , Weiss Susan R. 
Published: February 2017

ABSTRACT
The coronavirus (CoV) S protein requires cleavage by host cell proteases to mediate virus-cell and cell-cell fusion. Many strains of the murine coronavirus mouse hepatitis virus (MHV) have distinct, S-dependent organ and tissue tropisms despite using a common receptor, suggesting that they employ different cellular proteases for fusion. In support of this hypothesis, we found that inhibition of endosomal acidification only modestly decreased entry, and overexpression of the cell surface protease TMPRSS2 greatly enhanced entry, of the highly neurovirulent MHV strain JHM.SD relative to their effects on the reference strain, A59. However, TMPRSS2 overexpression decreased MHV structural protein expression, release of infectious particles, and syncytium formation, and endogenous serine protease activity did not contribute greatly to infection. We therefore investigated the importance of other classes of cellular proteases and found that inhibition of matrix metalloproteinase (MMP)- and a disintegrin and metalloprotease (ADAM)-family zinc metalloproteases markedly decreased both entry and cell-cell fusion. Suppression of virus by metalloprotease inhibition varied among tested cell lines and MHV S proteins, suggesting a role for metalloprotease use in strain-dependent tropism. We conclude that zinc metalloproteases must be considered potential contributors to coronavirus fusion.

IMPORTANCE
The family
Coronaviridae
includes viruses that cause two emerging diseases of humans, severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS), as well as a number of important animal pathogens. Because coronaviruses depend on host protease-mediated cleavage of their S proteins for entry, a number of protease inhibitors have been proposed as antiviral agents. However, it is unclear which proteases mediate
in vivo
infection. For example, SARS-CoV infection of cultured cells depends on endosomal acid pH-dependent proteases rather than on the cell surface acid pH-independent serine protease TMPRSS2, but Zhou et al. (Antiviral Res 116:76–84, 2015, doi:10.1016/j.antiviral.2015.01.011) found that a serine protease inhibitor was more protective than a cathepsin inhibitor in SARS-CoV-infected mice. This paper explores the contributions of endosomal acidification and various proteases to coronavirus infection and identifies an unexpected class of proteases, the matrix metalloproteinase and ADAM families, as potential targets for anticoronavirus therapy.
Inactivated Recombinant Rabies Viruses Displaying Canine Distemper Virus Glycoproteins Induce Protective Immunity against Both Pathogens
Authors: da Fontoura Budaszewski Renata , Hudacek Andrew , Sawatsky Bevan , Krämer Beate , Yin Xiangping , Schnell Matthias J. , von Messling Veronika 
Published: February 2017

ABSTRACTThe development of multivalent vaccines is an attractive methodology for the simultaneous prevention of several infectious diseases in vulnerable populations. Both canine distemper virus (CDV) and rabies virus (RABV) cause lethal disease in wild and domestic carnivores. While RABV vaccines are inactivated, the live-attenuated CDV vaccines retain residual virulence for highly susceptible wildlife species. In this study, we developed recombinant bivalent vaccine candidates based on recombinant vaccine strain rabies virus particles, which concurrently display the protective CDV and RABV glycoprotein antigens. The recombinant viruses replicated to near-wild-type titers, and the heterologous glycoproteins were efficiently expressed and incorporated in the viral particles. Immunization of ferrets with beta-propiolactone-inactivated recombinant virus particles elicited protective RABV antibody titers, and animals immunized with a combination of CDV attachment protein- and fusion protein-expressing recombinant viruses were protected from lethal CDV challenge. However, animals that were immunized with only a RABV expressing the attachment protein of CDV vaccine strain Onderstepoort succumbed to infection with a more recent wild-type strain, indicating that immune responses to the more conserved fusion protein contribute to protection against heterologous CDV strains.IMPORTANCERabies virus and canine distemper virus (CDV) cause high mortality rates and death in many carnivores. While rabies vaccines are inactivated and thus have an excellent safety profile and high stability, live-attenuated CDV vaccines can retain residual virulence in highly susceptible species. Here we generated recombinant inactivated rabies viruses that carry one of the CDV glycoproteins on their surface. Ferrets immunized twice with a mix of recombinant rabies viruses carrying the CDV fusion and attachment glycoproteins were protected from lethal CDV challenge, whereas all animals that received recombinant rabies viruses carrying only the CDV attachment protein according to the same immunization scheme died. Irrespective of the CDV antigens used, all animals developed protective titers against rabies virus, illustrating that a bivalent rabies virus-based vaccine against CDV induces protective immune responses against both pathogens.
Extreme Mutation Tolerance: Nearly Half of the Archaeal Fusellovirus Sulfolobus Spindle-Shaped Virus 1 Genes Are Not Required for Virus Function, Including the Minor Capsid Protein Gene
vp3
Authors: Iverson Eric A. , Goodman David A. , Gorchels Madeline E. , Stedman Kenneth M. 
Published: February 2017

ABSTRACT

Viruses infecting the
Archaea
harbor a tremendous amount of genetic diversity. This is especially true for the spindle-shaped viruses of the family
Fuselloviridae
, where >90% of the viral genes do not have detectable homologs in public databases. This significantly limits our ability to elucidate the role of viral proteins in the infection cycle. To address this, we have developed genetic techniques to study the well-characterized fusellovirus Sulfolobus spindle-shaped virus 1 (SSV1), which infects
Sulfolobus solfataricus
in volcanic hot springs at 80°C and pH 3. Here, we present a new comparative genome analysis and a thorough genetic analysis of SSV1 using both specific and random mutagenesis and thereby generate mutations in all open reading frames. We demonstrate that almost half of the SSV1 genes are not essential for infectivity, and the requirement for a particular gene correlates well with its degree of conservation within the
Fuselloviridae
. The major capsid gene
vp1
is essential for SSV1 infectivity. However, the universally conserved minor capsid gene
vp3
could be deleted without a loss in infectivity and results in virions with abnormal morphology.

IMPORTANCE
Most of the putative genes in the spindle-shaped archaeal hyperthermophile fuselloviruses have no sequences that are clearly similar to characterized genes. In order to determine which of these SSV genes are important for function, we disrupted all of the putative genes in the prototypical fusellovirus, SSV1. Surprisingly, about half of the genes could be disrupted without destroying virus function. Even deletions of one of the known structural protein genes that is present in all known fuselloviruses,
vp3
, allows the production of infectious viruses. However, viruses lacking
vp3
have abnormal shapes, indicating that the
vp3
gene is important for virus structure. Identification of essential genes will allow focused research on minimal SSV genomes and further understanding of the structure of these unique, ubiquitous, and extremely stable archaeal viruses.
Impact of rapid ultrafiltration rate on changes in the echocardiographic left atrial volume index in patients undergoing haemodialysis: a longitudinal observational study
Authors: Kim Jwa-Kyung , Song Young Rim , Park GunHa , Kim Hyung Jik , Kim Sung Gyun 
Published: February 2017

ObjectiveOptimal fluid management is essential when caring for a patient on haemodialysis (HD). However, if the fluid removal is too rapid, the resultant higher ultrafiltration rate (UFR) disadvantageously promotes haemodynamic instability and cardiac injury. We evaluated the effects of a rapid UFR on changes in the echocardiographic left atrial volume index (LAVI) over a period of time.DesignLongitudinal observational study.Setting and participantsA total of 124 new patients on HD.InterventionsEchocardiography was performed at baseline and repeated after 19.7 months (range 11.3–23.1 months). Changes in LAVI (ΔLAVI/year, mL/m2/year) were calculated. The UFR was expressed in mL/hour/kg, and we used the mean UFR over 30 days (∼12–13 treatments).Main outcome measuresThe 75th centile of the ΔLAVI/year distribution was regarded as a ‘pathological’ increment.ResultsThe mean interdialytic weight gain was 1.73±0.94 kg, and the UFR was 8.01±3.87 mL/hour/kg. The significant pathological increment point in ΔLAVI/year was 4.89 mL/m2/year. Correlation analysis showed that ΔLAVI/year was closely related to the baseline blood pressure, haemoglobin level, residual renal function and UFR. According to the receiver operating characteristics curve, the ‘best’ cut-off value of UFR for predicting the pathological increment was 10 mL/hour/kg, with an area under the curve of 0.712. In multivariate analysis, systolic blood pressure, a history of coronary artery disease, haemoglobin <10 g/dL and high UFR were significant predictors. An increase of 1 mL/hour/kg in the UFR was associated with a 22% higher risk of a worsening LAVI (OR 1.22, 95% CI 1.05 to 1.41).ConclusionsAn increased haemodynamic load could affect left atrial remodelling in incident patients on HD. Thus, close monitoring and optimal control of UFR are needed.