bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ledipasvir/sofosbuvir fixed‐dose combination tablet in Taiwanese patients with chronic genotype 1 hepatitis C virus
Authors: Chuang Wan‐Long , Chien Rong‐Nan , Peng Cheng‐Yuan , Chang Ting‐Tsung , Lo Gin‐Ho , Sheen I‐Shyan , Wang Horng‐Yuan , Chen Jyh‐Jou , Yang Jenny C. , Knox Steven J. , Gao Bing , Garrison Kimberly L. , Mo Hongmei , Pang Phillip S. , Hsu Yu‐Chun , Hu Tsung‐Hui , Chu Chi‐Jen , Kao Jia‐Horng 
Published: February 2016

AbstractBackground and Aim:Pegylated‐interferon‐alpha plus ribavirin is the current standard‐of‐care regimen for treating chronic hepatitis C virus (HCV) infection in Taiwan; however, interferon‐based regimens can be poorly tolerated. The interferon‐free, two‐drug, fixed‐dose combination tablet ledipasvir/sofosbuvir is approved in Europe, the USA, and Japan for treating chronic genotype 1 HCV infection. Little is known about its efficacy/safety in Taiwanese patients.Methods:In this multicenter, open‐label, phase 3b (NCT02021656) study, 85 Taiwanese patients (n = 42, treatment‐naïve; n = 43, treatment‐experienced) with chronic genotype 1 HCV infection (±compensated cirrhosis) received 12 weeks of ledipasvir/sofosbuvir fixed‐dose combination tablet. The primary efficacy end point was the proportion of patients with sustained virologic response 12 weeks after treatment discontinuation (SVR12). Safety and pharmacokinetic data were collected.Results:The overall SVR12 rate was 98% (83/85), with 100% (42/42) and 95% (41/43) of treatment‐naïve and treatment‐experienced patients, respectively, achieving SVR12. There were no on‐treatment virologic failures. One patient relapsed after treatment discontinuation; one patient withdrew consent on day 2. The most common treatment‐emergent adverse event (AE) was headache (14%, 12/85). There was one grade 3 AE (small cell lung cancer unrelated to ledipasvir/sofosbuvir), no grade 4 AEs, and four grade 3–4 laboratory abnormalities. Only the patient with small cell lung cancer prematurely discontinued treatment. Two patients reported three serious AEs; none was considered related to ledipasvir/sofosbuvir.Conclusions:Data from this phase 3b study suggest that 12 weeks of once‐daily treatment with the interferon‐free, ribavirin‐free regimen ledipasvir/sofosbuvir is effective and well‐tolerated in Taiwanese patients with chronic genotype 1 HCV infection, irrespective of treatment history.
Effects of the Addition of Titanium Dioxide and Silaned Silica Nanoparticles on the Mechanical Properties of Maxillofacial Silicones
Authors: Cevik Pinar , Eraslan Oguz 
Published: February 2016

AbstractPurposeSilicone‐based elastomeric materials are commonly used to fabricate maxillofacial prostheses. The aim of this study was to evaluate the effect of different types of silica and nanosized titanium dioxide addition on the mechanical properties of two RTV silicone elastomers.Materials and MethodsA‐2000 and A‐2006 silicone elastomers were used, and each was divided into four subgroups (n = 5). The first group was the control without additives. Other groups were titanium dioxide, fumed silica, and silaned silica. Each specimen was prepared in compliance with the manufacturer's instructions for the tensile strength, percent elongation, tear resistance, and the hardness tests according to ISO and ASTM standards. A factorial ANOVA with pairwise interaction indicated that the pattern for all four outcomes of the materials was different for A‐2000 and A‐2006 (p < 0.05). Therefore, the average outcome values for the materials within silicone elastomers were then analyzed by Tukey HSD. For the hardness test results, Kruskal‐Wallis and Mann‐Whitney U test methods were used. The level of statistical significance was p < 0.05.ResultsThere was a statistically significant interaction (p < 0.05) between materials and silicone type for all four tests (tensile strength, tear, hardness, percent elongation). The hydrophobic silica group had significantly higher tensile strength than TiO2 for A‐2000. The fumed hydrophilic silica group had significantly higher tensile strength than TiO2 for A‐2006. Most of silica specimens had higher tensile strength when compared with the control and TiO2 groups for A‐2000 and A‐2006 silicones. The TiO2 group had the highest hardness value for A‐2000 while the lowest hardness value for A‐2006 (p < 0.05). There was no significant difference of tear strength among the type of additives (p > 0.05) for A‐2000. The fumed silica and TiO2 groups had significantly higher tear strength than the control group for A‐2006. The fumed silica and the hydrophobic silica groups had significantly higher percent elongation than the control group (p < 0.05) for A‐2000. The TiO2 group had the lowest percent elongation for A‐2006.ConclusionsResults in this in vitro study may clarify future studies about the effect of different additives on the physical and mechanical properties of maxillofacial elastomers. There is a great interest in the effect of a new‐generation hydrophobic silica incorporation into A‐2000 silicone as well as the effect of fumed hydrophilic silica incorporation into A‐2006 silicone. Future research should be supported with more in vitro trials in different percentages of such additives used in this study.
Signaling by the heavy‐metal sensor CusS involves rearranged helical interactions in specific transmembrane regions
Authors: Fung Danny Ka Chun , Ma Yongzheng , Xia Tingying , Luk Jakson Chak Hon , Yan Aixin 
Published: February 2016

SummaryTwo‐component systems (TCSs) play important roles in the adaptation of bacteria to stress. Despite their increasingly well understood mechanistic features, it remains poorly understood how TCSs transduce signals across membranes. Here, we use the E. coli Cu/Ag‐responsive CusSR TCS as a model to investigate the roles of CusS transmembrane (TM) residues. Proline scanning of TM1 domain led to identification of the T17P, F18P, and S21P variants, which display higher kinase activities relative to wild type. A single point mutation, V202G, in the adjacent TM2 domain specifically suppresses the hyperactivities of these mutants. Disulfide crosslinking analysis demonstrated that T17 and V202 are situated in close proximity, and Cys residues substituted at those two positions form exclusive intramolecular crosslinks when CusS is in the signaling‐inactive state. In the signaling‐active variant of CusS, however, only intermolecular crosslinking between the two Cys residues could be observed, suggesting that destabilization of an intramolecular constraint and a subsequent rearrangement of helical interactions in this TM region is involved in the activation of CusS. An analogous TM helical interface in the P. aeruginosa heavy metal sensor kinase CzcS is also observed. Together, these results suggested a conserved transmembrane signal transduction mechanism in the heavy metal sensing TCSs.
A mass stranding of seven Longman's beaked whales (Indopacetus pacificus) in New Caledonia, South Pacific
Authors: Garrigue Claire , Oremus Marc , Dodémont Rémi , Bustamante Paco , Kwiatek Olivier , Libeau Geneviève , Lockyer Christina , Vivier Jean Christophe , Dalebout Merel L. 
Published: February 2016

AbstractSeven Longman's beaked whales (Indopacetus pacificus) stranded together in southern New Caledonia on 16 November 2013 (one adult male, two adult females, two subadult females, one calf, and one unknown). At this time, we have no evidence to suggest that this event was an “atypical” mass stranding associated with active naval sonar or other anthropogenic activities. The adult females were slightly larger (618–640 cm) than the adult male (590 cm). The length of the calf (ca. 300 cm) suggests it was less than a year old. Five of the whales were sampled for mitochondrial (mt) DNA analysis to confirm species identification. All shared the same haplotype over 680 bp of the mtDNA control region. High concentrations of Hg, Fe, Se, Zn (all in the liver), and Cd (in the kidneys) were detected. Necropsies revealed plastic debris in the stomach of two of the whales. One of these same whales had chronic gastritis while the other had acute pleurisy and also tested positive for morbillivirus. This infection may have been a major factor behind this mass stranding event.
Dust mite allergen Der f 4: Expression, characterization, and IgE binding in pediatric asthma
Authors: Cui Yu‐bao , Yu Li‐li , Teng Fei‐xiang , Wang Nan , Zhou Ying , Yang Li , Zhang Cheng‐bo 
Published: February 2016

AbstractBackgroundHouse dust mite hypersensitivity affects millions of people worldwide, and although many allergens produced by house dust mite species have been identified, some of the less potent allergens remain to be studied.MethodsThe full‐length cDNA encoding the group 4 allergen of the house dust mite species Dermatophagoides farinae (Der f 4) was generated through degenerate primer‐based PCR, 5′ RACE, and 3′ RACE, and the cDNA fragment was cloned into an expression vector for nucleotide sequencing. Following codon optimization and removal of the signal peptide sequence, the mature gene fragment was subcloned into pET‐28b (+) and transfected into E. coli BL21 cells for expression. The recombinant protein was purified by nickel affinity chromatography, identified by SDS‐PAGE, Western blotting, and MALDI‐TOF, and tested by ELISA for IgE reactivity with sera from individuals with asthma. Bioinformatics analyses were used to identify features of Der f 4.ResultsSDS‐PAGE and Western blotting of the codon‐optimized expression product showed a specific band. The mature recombinant Der f 4 was characterized as a stable and hydrophilic 57.9‐kDa protein, and its secondary structure comprised alpha helix (25.3%), extended strand (22.51%), and random coils (52.19%). The structure of the recombinant protein was consistent with that of α‐amylase. Among 27 pediatric asthma patients, 40.74% exhibited reactivity to rDer f 4 by ELISA.ConclusionsThis initial cloning and characterization of the Der f 4 allergen serves as a foundation for future studies into the clinical importance and application of this protein for house dust mite allergy.
The effect of internalization and other psychologic factors on the remission and severity of wheeze in children
Authors: Feitosa Caroline A. , Santos Darci N. , Barreto Maurício L. , Rodrigues Laura C. 
Published: February 2016

AbstractBackgroundAsthma prevalence in Latin America is high and continues to increase. There is evidence that the psychologic characteristics of the child are associated with greater asthma morbidity. This study aimed to investigate the independent effect of internalizing/externalizing problems on two asthma/wheeze outcomes: (i) remission and (ii) progression to severity on Latin American children with mild asthma symptoms at baseline.MethodsThis was a prospective study in a cohort of 371 asthmatic children living in a poor urban area in Salvador, Brazil. The psychologic characteristics of the child were assessed using the Child Behavior Checklist (CBCL), and wheezing was defined using the ISAAC questionnaire at the start and end of follow‐up. A multiple logistic regression model with random effects was used to examine the association between the psychologic components and both outcomes.ResultsRemission of symptoms of wheeze was observed among 229 (61.73%) children. Remission was 56% lower among children with internalizing problems (OR = 0.54, 95% CI 0.33–0.87, p = 0.01). In addition, we found that 19 (8.76%) of the children acquired severe symptoms during follow‐up and there was strong evidence of the effect of internalizing problems in increasing the risk of progression to severe wheeze symptoms (OR = 4.03, 95% CI 1.39–11.70, p = 0.01).ConclusionsChildren with internalizing problems but not externalizing had less remission of wheezing, and a higher risk of acquiring severe symptoms. These results highlight the importance of psychologic care for children with asthma, to improve the prognosis of this condition.
Non‐typeable Haemophilus influenzae purulent pericarditis in a child with cystic fibrosis
Authors: Downes Kevin J , Abulebda Kamal , Siracusa Christopher , Moore Ryan , Staat Mary A , Poynter Sue E 
Published: February 2016

AbstractEarly airway colonization and infection with Haemophilus influenzae in children with cystic fibrosis (CF) is common. Although the pathogenicity of non‐typeable H. influenzae (NTHi) in patients with CF is controversial, this organism can cause both upper and lower respiratory tract infections. Extra‐pulmonary disease, however, is rare. Purulent pericarditis is a suppurative complication of bacterial infection of the pericardial space that can arise as a result of direct extension from an adjacent infection. We describe a case of purulent pericarditis due to NTHi in a young child with CF that developed as a complication of inadequately treated bronchopneumonia.
A method for estimating microporosity of fine‐grained sediments and sedimentary rocks via scanning electron microscope image analysis
Authors: Nole Michael , Daigle Hugh , Milliken Kitty L. , Prodanović Maša 
Published: February 2016

AbstractThis study presents a method of two‐dimensional scanning electron microscope image analysis that directly quantifies microporosity abundance in clay‐rich, fine‐grained sediments. The method is novel in that it is specifically designed to circumvent the challenge to porosity quantification posed by mineral surface charging and topographical artifacts created during Ar‐ion cross‐section polishing. It utilizes the finding that differences in circularity values can be used to distinguish micropores from blemishes in a thresholded image. This method is powerful because it is fast and provides a direct microporosity estimation technique to augment or replace experimental data. The pore size range to which the method is applicable is clear and can be selected depending on the application of the analysis. When used appropriately, the method can be implemented on microporous sediments and sedimentary rock in general. The method is developed using marine muds of Pliocene and Miocene ages from the Nankai margin (burial depths from approximately 200 to 1100 m). The close match between imaging‐derived microporosity and bulk N2 microporosity measurements shows that porosity in these young and relatively shallowly buried sediments is dominated by pores of sizes that can be imaged by scanning electron microscopy. In Kumano, forearc basin sediments of the Nankai Trough, results of this method show a significant increase in microporosity with burial depth, probably due to microporosity preservation during compaction and possibly early volcanic ash diagenesis.
Physical exercise increases adult hippocampal neurogenesis in male rats provided it is aerobic and sustained
Authors: Nokia Miriam S. , Lensu Sanna , Ahtiainen Juha P. , Johansson Petra P. , Koch Lauren G. , Britton Steven L. , Kainulainen Heikki 
Published: February 2016

Key points
Aerobic exercise, such as running, enhances adult hippocampal neurogenesis (AHN) in rodents.
Little is known about the effects of high‐intensity interval training (HIT) or of purely anaerobic resistance training on AHN.
Here, compared with a sedentary lifestyle, we report a very modest effect of HIT and no effect of resistance training on AHN in adult male rats.
We found the most AHN in rats that were selectively bred for an innately high response to aerobic exercise that also run voluntarily and increase maximal running capacity.
Our results confirm that sustained aerobic exercise is key in improving AHN.
AbstractAerobic exercise, such as running, has positive effects on brain structure and function, such as adult hippocampal neurogenesis (AHN) and learning. Whether high‐intensity interval training (HIT), referring to alternating short bouts of very intense anaerobic exercise with recovery periods, or anaerobic resistance training (RT) has similar effects on AHN is unclear. In addition, individual genetic variation in the overall response to physical exercise is likely to play a part in the effects of exercise on AHN but is less well studied. Recently, we developed polygenic rat models that gain differentially for running capacity in response to aerobic treadmill training. Here, we subjected these low‐response trainer (LRT) and high‐response trainer (HRT) adult male rats to various forms of physical exercise for 6–8 weeks and examined the effects on AHN. Compared with sedentary animals, the highest number of doublecortin‐positive hippocampal cells was observed in HRT rats that ran voluntarily on a running wheel, whereas HIT on the treadmill had a smaller, statistically non‐significant effect on AHN. Adult hippocampal neurogenesis was elevated in both LRT and HRT rats that underwent endurance training on a treadmill compared with those that performed RT by climbing a vertical ladder with weights, despite their significant gain in strength. Furthermore, RT had no effect on proliferation (Ki67), maturation (doublecortin) or survival (bromodeoxyuridine) of new adult‐born hippocampal neurons in adult male Sprague–Dawley rats. Our results suggest that physical exercise promotes AHN most effectively if the exercise is aerobic and sustained, especially when accompanied by a heightened genetic predisposition for response to physical exercise.
U.S. Ebola Treatment Center Clinical Laboratory Support
Authors: Jelden Katelyn C. , Iwen Peter C. , Herstein Jocelyn J. , Biddinger Paul D. , Kraft Colleen S. , Saiman Lisa , Smith Philip W. , Hewlett Angela L. , Gibbs Shawn G. , Lowe John J. 
Published: February 2016

ABSTRACT
Fifty-five hospitals in the United States have been designated Ebola treatment centers (ETCs) by their state and local health authorities. Designated ETCs must have appropriate plans to manage a patient with confirmed Ebola virus disease (EVD) for the full duration of illness and must have these plans assessed through a CDC site visit conducted by an interdisciplinary team of subject matter experts. This study determined the clinical laboratory capabilities of these ETCs. ETCs were electronically surveyed on clinical laboratory characteristics. Survey responses were returned from 47 ETCs (85%). Forty-one (87%) of the ETCs planned to provide some laboratory support (e.g., point-of-care [POC] testing) within the room of the isolated patient. Forty-four (94%) ETCs indicated that their hospital would also provide clinical laboratory support for patient care. Twenty-two (50%) of these ETC clinical laboratories had biosafety level 3 (BSL-3) containment. Of all respondents, 34 (72%) were supported by their jurisdictional public health laboratory (PHL), all of which had available BSL-3 laboratories. Overall, 40 of 44 (91%) ETCs reported BSL-3 laboratory support via their clinical laboratory and/or PHL. This survey provided a snapshot of the laboratory support for designated U.S. ETCs. ETCs have approached high-level isolation critical care with laboratory support in close proximity to the patient room and by distributing laboratory support among laboratory resources. Experts might review safety considerations for these laboratory testing/diagnostic activities that are novel in the context of biocontainment care.
Evaluation of Polymorphic Locus Sequence Typing for Candida glabrata Epidemiology
Authors: Katiyar Santosh , Shiffrin Eric , Shelton Celeste , Healey Kelley , Vermitsky John-Paul , Edlind Tom 
Published: February 2016

ABSTRACT

The opportunistic yeast
Candida glabrata
is increasingly refractory to antifungal treatment or prophylaxis and relatedly is increasingly implicated in health care-associated infections. To elucidate the epidemiology of these infections, strain typing is required. Sequence-based typing provides multiple advantages over length-based methods, such as pulsed-field gel electrophoresis (PFGE); however, conventional multilocus sequence typing (targeting 6 conserved loci) and whole-genome sequencing are impractical for routine use. A commercial sequence-based typing service for
C. glabrata
that targets polymorphic tandem repeat-containing loci has recently been developed. These CgMT-J and CgMT-M services were evaluated with 56 epidemiologically unrelated isolates, 4 to 7 fluconazole-susceptible or fluconazole-resistant isolates from each of 5 center A patients, 5 matched pairs of fluconazole-susceptible/resistant isolates from center B patients, and 7 isolates from a center C patient who responded to then failed caspofungin therapy. CgMT-J and CgMT-M generated congruent results, resolving isolates into 24 and 20 alleles, respectively. Isolates from all but one of the center A patients shared the same otherwise rare alleles, suggesting nosocomial transmission. Unexpectedly, Pdr1 sequencing showed that resistance arose independently in each patient. Similarly, most isolates from center B also clustered together; however, this may reflect a dominant clone since their alleles were shared by multiple unrelated isolates. Although distinguishable by their echinocandin susceptibilities, all isolates from the center C patient shared alleles, in agreement with the previously reported relatedness of these isolates based on PFGE. Finally, we show how phylogenetic clusters can be used to provide surrogate parents to analyze the mutational basis for antifungal resistance.
Controlled Evaluation of the New BacT/Alert Virtuo Blood Culture System for Detection and Time to Detection of Bacteria and Yeasts
Authors: Altun Osman , Almuhayawi Mohammed , Lüthje Petra , Taha Rubina , Ullberg Måns , Özenci Volkan 
Published: February 2016

ABSTRACT

We compared the newly approved BacT/Alert Virtuo blood culture system to the BacT/Alert 3D system using 115 clinical bacterial and fungal isolates in 784 simulated blood culture bottles. The time to detection was reduced by roughly 20% in the Virtuo system (
P
< 0.0001) while the detection rate did not differ.
The Barrier to Autointegration Factor: Interlocking Antiviral Defense with Genome Maintenance
Authors: Wiebe Matthew S. , Jamin Augusta 
Published: February 2016

ABSTRACT
Intrinsic defenses targeting foreign DNA are one facet of the cellular armament tasked with protecting host genomic integrity. The DNA binding protein BAF (barrier to autointegration factor) contributes to multiple aspects of genome maintenance and intercepts retrovirus, poxvirus, and herpesvirus genomes during infection. In this gem, we discuss the unique position BAF occupies at the virus-host interface and how both viral and cellular mechanisms may regulate its capacity to act as a pro- or antiviral effector targeting viral DNA.
Virus and Host Mechanics Support Membrane Penetration and Cell Entry
Authors: Greber Urs F. 
Published: February 2016

ABSTRACT
Viruses are quasi-inert macromolecular assemblies. Their metastable conformation changes during entry into cells, when chemical and mechanical host cues expose viral membrane-interacting proteins. This leads to membrane rupture or fusion and genome uncoating. Importantly, virions tune their physical properties and enhance penetration and uncoating. For example, influenza virus softens at low pH to uncoat. The stiffness and pressure of adenovirus control uncoating and membrane penetration. Virus and host mechanics thus present new opportunities for antiviral therapy.