bluuebunny/crossref_metadata_2025_split huggingface dataset:
Determination of Disk Diffusion and MIC Quality Control Guidelines for Solithromycin, a Novel Fluoroketolide Antibacterial, against Neisseria gonorrhoeae
Authors: Riedel Stefan , Ross James E. , Farrell David J. , Flamm Robert K. , Jones Ronald N. 
Published: September 2015

ABSTRACT

This solithromycin quality control study was performed to establish quality control (QC) ranges for the
N. gonorrhoeae
ATCC 49226 control strain for MIC agar dilution testing (AD) and zones by disk diffusion testing (DD). The following ranges were established: AD, 0.03 to 0.25 μg/ml, and DD, 33 to 43 mm. In January 2015, the CLSI Subcommittee on Antimicrobial Susceptibility Testing approved these ranges, which will be important when evaluating solithromycin against clinical isolates of
N. gonorrhoeae
.
Vaccine-Derived Neutralizing Antibodies to the Human Cytomegalovirus gH/gL Pentamer Potently Block Primary Cytotrophoblast Infection
Authors: Chiuppesi Flavia , Wussow Felix , Johnson Erica , Bian Chao , Zhuo Meng , Rajakumar Augustine , Barry Peter A. , Britt William J. , Chakraborty Rana , Diamond Don J. 
Published: September 2015

ABSTRACTHuman cytomegalovirus (HCMV) elicits neutralizing antibodies (NAb) of various potencies and cell type specificities to prevent HCMV entry into fibroblasts (FB) and epithelial/endothelial cells (EpC/EnC). NAb targeting the major essential envelope glycoprotein complexes gB and gH/gL inhibit both FB and EpC/EnC entry. In contrast to FB infection, HCMV entry into EpC/EnC is additionally blocked by extremely potent NAb to conformational epitopes of the gH/gL/UL128/130/131A pentamer complex (PC). We recently developed a vaccine concept based on coexpression of all five PC subunits by a single modified vaccinia virus Ankara (MVA) vector, termed MVA-PC. Vaccination of mice and rhesus macaques with MVA-PC resulted in a high titer and sustained NAb that blocked EpC/EnC infection and lower-titer NAb that inhibited FB entry. However, antibody function responsible for the neutralizing activity induced by the MVA-PC vaccine is uncharacterized. Here, we demonstrate that MVA-PC elicits NAb with cell type-specific neutralization potency and antigen recognition pattern similar to human NAb targeting conformational and linear epitopes of the UL128/130/131A subunits or gH. In addition, we show that the vaccine-derived PC-specific NAb are significantly more potent than the anti-gH NAb to prevent HCMV spread in EpC and infection of human placental cytotrophoblasts, cell types thought to be of critical importance for HCMV transmission to the fetus. These findings further validate MVA-PC as a clinical vaccine candidate to elicit NAb that resembles those induced during HCMV infection and provide valuable insights into the potency of PC-specific NAb to interfere with HCMV cell-associated spread and infection of key placental cells.IMPORTANCEAs a consequence of the leading role of human cytomegalovirus (HCMV) in causing permanent birth defects, developing a vaccine against HCMV has been assigned a major public health priority. We have recently introduced a vaccine strategy based on a widely used, safe, and well-characterized poxvirus vector platform to elicit potent and durable neutralizing antibody (NAb) responses targeting the HCMV envelope pentamer complex (PC), which has been suggested as a critical component for a vaccine to prevent congenital HCMV infection. With this work, we confirm that the NAb elicited by the vaccine vector have properties that are similar to those of human NAb isolated from individuals chronically infected with HCMV. In addition, we show that PC-specific NAb have potent ability to prevent infection of key placental cells that HCMV utilizes to cross the fetal-maternal interface, suggesting that NAb targeting the PC may be essential to prevent HCMV vertical transmission.
Mumps Virus Is Released from the Apical Surface of Polarized Epithelial Cells, and the Release Is Facilitated by a Rab11-Mediated Transport System
Authors: Katoh Hiroshi , Nakatsu Yuichiro , Kubota Toru , Sakata Masafumi , Takeda Makoto , Kidokoro Minoru 
Published: September 2015

ABSTRACT

Mumps virus (MuV) is an airborne virus that causes a systemic infection in patients.
In vivo
, the epithelium is a major replication site of MuV, and thus, the mode of MuV infection of epithelial cells is a subject of interest. Our data in the present study showed that MuV entered polarized epithelial cells via both the apical and basolateral surfaces, while progeny viruses were predominantly released from the apical surface. In polarized cells, intracellular transport of viral ribonucleoprotein (vRNP) complexes was dependent on Rab11-positive endosomes, and vRNP complexes were transported to the apical membrane. Expression of a dominant negative form of Rab11 (Rab11S25N) reduced the progeny virus release in polarized cells but not in nonpolarized cells. Although in this way these effects were correlated with cell polarity, Rab11S25N did not modulate the direction of virus release from the apical surface. Therefore, our data suggested that Rab11 is not a regulator of selective apical release of MuV, although it acts as an activator of virus release from polarized epithelial cells. In addition, our data and previous studies on Sendai virus, respiratory syncytial virus, and measles virus suggested that selective apical release from epithelial cells is used by many paramyxoviruses, even though they cause either a systemic infection or a local respiratory infection.

IMPORTANCE
Mumps virus (MuV) is the etiological agent of mumps and causes a systemic infection. However, the precise mechanism by which MuV breaks through the epithelial barriers and achieves a systemic infection remains unclear. In the present study, we show that the entry of MuV is bipolar, while the release is predominantly from the apical surface in polarized epithelial cells. In addition, the release of progeny virus was facilitated by a Rab11-positive recycling endosome and microtubule network. Our data provide important insights into the mechanism of transmission and pathogenesis of MuV.
Audit of Clinical and Functional Outcomes of Arthroscopic Resection of Wrist Ganglions
Authors: Chung Sze-Ryn , Tay Shian Chao 
Published: September 2015

Background: The purpose of this study is to audit the clinical and functional outcomes of arthroscopic ganglionectomy (AG) in our centre.Methods: A retrospective study was conducted on all 29 patients who underwent AG from 2007 to 2012 with a mean clinic and telephone follow-up duration of 6 months and 32 months respectively.Results: A total of 29 patients (17 women and 12 men) with a mean age of 38 years underwent AG. 15 patients (52%) had associated pain with the lump, 24 out of 29 patients (83%) had preoperative ultrasound to confirm the diagnosis. All patients had preoperative wrist radiographs that showed no chronic carpal instability and bony pathology. 26 out of 29 patients (90%) had dorsal wrist ganglions and 3 patients (10%) had volar wrist ganglions. 15 out of 24 ganglions (62.5%) were multiloculated. Mean ganglion size clinically and through wrist ultrasound was 2.5 cm and 1.8 cm respectively. During arthroscopy, ganglion stalk was identified in 14 patients (48%). Average operating time was 69.5 minutes. Intraoperatively, 24 out of 29 patients (83%) had wrist synovitis and 26 patients (90%) had associated carpal ligament laxity. 97% of cases were successfully resected arthroscopically. Recurrence rate was 10% (3 cases). There was no significant difference between preoperative and postoperative range of motion of wrists - the mean wrist flexion ranged from 63 to 59 degrees pre and postoperatively, and the mean wrist extension ranged from 66 to 64 degrees pre and postoperatively. Overall grip strength improved from 27 kg to 32 kg ([Formula: see text]), and there was also a significant improvement in pain scores pre and post-operatively from visual analogue scale (VAS) score of 0.8 to 0.3 ([Formula: see text]). No major intra or post-operative complications occurred. All patients were satisfied in terms of cosmesis.Conclusions: AG is a safe and reliable alternative to open resection of wrist ganglions. In addition, it can be used as a diagnostic and therapeutic tool for other wrist conditions.
Bone Marrow Derived Mesenchymal Stem Cell Augmentation of Rabbit Flexor Tendon Healing
Authors: He Min , Gan Aaron Wei Tat , Lim Aymeric Yu Tang , Goh James Cho Hong , Hui James Hoi Po , Chong Alphonsus Khin Sze 
Published: September 2015

Background: This study investigated the effect of mesenchymal stem cell implantation on flexor tendon healing using a rabbit model of flexor tendon repair. Specifically, we compared the difference between autologous and allogeneic stem cells. The influence of cell number on the outcome of flexor tendon healing was also investigated. Methods: Repaired tendons on the rear paws of rabbits were randomly assigned into four groups: control group, 1 million autologous cells, 1 million allogeneic cells, and 4 million allogeneic cells. Rabbits were sacrificed at 3 or 8 weeks after surgery. Results: Implantation of 4 million stem cells resulted in a significant increase in range of motion compared with control group at three weeks after surgery. The positive staining of collagen I in healing tendons was enhanced in stem cell treated groups three weeks after surgery. However, stem cells did not improve biomechanical properties of flexor tendons. Conclusions: High dose stem cells attenuated adhesions in the early time point following flexor tendon repair. Further work is needed determine the value of stem cell therapy in flexor tendon healing in humans.
Dll4 Blockade in Stromal Cells Mediates Antitumor Effects in Preclinical Models of Ovarian Cancer
Authors: Kuhnert Frank , Chen Guoying , Coetzee Sandra , Thambi Nithya , Hickey Carlos , Shan Jing , Kovalenko Pavel , Noguera-Troise Irene , Smith Eric , Fairhurst Jeanette , Andreev Julian , Kirshner Jessica R. , Papadopoulos Nicholas , Thurston Gavin 
Published: September 2015

Abstract
The Notch ligand delta-like 4 (Dll4) has been identified as a promising target in tumor angiogenesis in preclinical studies, and Dll4 inhibitors have recently entered clinical trials for solid tumors, including ovarian cancers. In this study, we report the development of REGN421 (enoticumab), a fully human IgG1 monoclonal antibody that binds human Dll4 with sub-nanomolar affinity and inhibits Notch signaling. Administering REGN421 to immunodeficient mice engineered to express human Dll4 inhibited the growth of several human tumor xenografts in association with the formation of nonfunctional tumor blood vessels. In ovarian tumor xenograft models, Dll4 was expressed specifically by the tumor endothelium, and Dll4 blockade by human-specific or mouse-specific Dll4 antibodies exerted potent antitumor activity, which relied entirely on targeting Dll4 expressed by tumor stromal cells but not by the tumor cells themselves. However, Dll4 blockade reduced Notch signaling in both blood vessels and tumor cells surrounding the blood vessels, suggesting that endothelial-expressed Dll4 might induce Notch signaling in adjacent ovarian tumor cells. The antitumor effects of targeting Dll4 were augmented significantly by simultaneous inhibition of VEGF signaling, whereas this combined blockade reversed normal organ vascular changes induced by Dll4 blockade alone. Overall, our findings deepen the rationale for antibody-based strategies to target Dll4 in ovarian cancers, especially in combination with VEGF blockade. Cancer Res; 75(19); 4086–96. ©2015 AACR.
Metformin Use and Risk of Colorectal Adenoma after Polypectomy in Patients with Type 2 Diabetes Mellitus
Authors: Marks Amy R. , Pietrofesa Ralph A. , Jensen Christopher D. , Zebrowski Alexis , Corley Douglas A. , Doubeni Chyke A. 
Published: September 2015

AbstractBackground: Existing literature suggests that metformin, the most commonly used biguanide, may lower colorectal cancer risk. Because most colorectal cancers originate in precancerous adenomas, we examined whether metformin use lowered colorectal adenoma risk after polypectomy in patients with type-2 diabetes.Methods: Retrospective cohort study of 40- to 89-year-old Kaiser Permanente Northern California patients who had type 2 diabetes, and ≥1 adenoma detected at baseline colonoscopy during 2000 to 2009 and a repeat colonoscopy 1 to 10 years from baseline adenoma diagnosis through 2012. Cox models evaluated the association between metformin use during follow-up and subsequent adenoma diagnoses, controlling for age, race/ethnicity, sex, body mass index, and repeat examination indication.Results: Study included 2,412 patients followed for a median of 4.5 years; cumulatively, 1,117 (46%) patients had ≥1 adenoma at repeat colonoscopy. Compared with patients not receiving diabetes medications (n = 1,578), metformin-only use (n = 457) was associated with lower adenoma recurrence risk [adjusted HR, 0.76; 95% confidence interval (CI), 0.65–0.89], and the association was stronger with increasing total metformin dose [quartile (Q) 1: HR, 0.90; 95% CI, 0.72–1.12; Q2: HR, 0.89; 95% CI, 0.70–1.12; Q3: HR, 0.80; 95% CI, 0.63–1.01; Q4: HR, 0.50; 95% CI, 0.42–0.60, Ptrend &lt; 0.001]. Findings were unchanged in sensitivity analyses, including evaluating only outcomes during the 3- to 10-year period from baseline.Conclusion: Our study suggests a potential benefit of metformin use in lowering the risk of subsequent adenomas after polypectomy in patients with type 2 diabetes.Impact: Metformin may lower colorectal cancer risk by reducing the formation of precancerous lesions, reinforcing the potential additional benefits of its use. Cancer Epidemiol Biomarkers Prev; 24(11); 1692–8. ©2015 AACR.
Using Whole-Exome Sequencing to Identify Genetic Markers for Carboplatin and Gemcitabine-Induced Toxicities
Authors: Gréen Henrik , Hasmats Johanna , Kupershmidt Ilya , Edsgärd Daniel , de Petris Luigi , Lewensohn Rolf , Blackhall Fiona , Vikingsson Svante , Besse Benjamin , Lindgren Andrea , Brandén Eva , Koyi Hirsh , Peterson Curt , Lundeberg Joakim 
Published: September 2015

Abstract
Purpose: Chemotherapies are associated with significant interindividual variability in therapeutic effect and adverse drug reactions. In lung cancer, the use of gemcitabine and carboplatin induces grade 3 or 4 myelosuppression in about a quarter of the patients, while an equal fraction of patients is basically unaffected in terms of myelosuppressive side effects. We therefore set out to identify genetic markers for gemcitabine/carboplatin-induced myelosuppression.
Experimental Design: We exome sequenced 32 patients that suffered extremely high neutropenia and thrombocytopenia (grade 3 or 4 after first chemotherapy cycle) or were virtually unaffected (grade 0 or 1). The genetic differences/polymorphism between the groups were compared using six different bioinformatics strategies: (i) whole-exome nonsynonymous single-nucleotide variants association analysis, (ii) deviation from Hardy–Weinberg equilibrium, (iii) analysis of genes selected by a priori biologic knowledge, (iv) analysis of genes selected from gene expression meta-analysis of toxicity datasets, (v) Ingenuity Pathway Analysis, and (vi) FunCoup network enrichment analysis.
Results: A total of 53 genetic variants that differed among these groups were validated in an additional 291 patients and were correlated to the patients' myelosuppression. In the validation, we identified rs1453542 in OR4D6 (P = 0.0008; OR, 5.2; 95% CI, 1.8–18) as a marker for gemcitabine/carboplatin-induced neutropenia and rs5925720 in DDX53 (P = 0.0015; OR, 0.36; 95% CI, 0.17–0.71) as a marker for thrombocytopenia. Patients homozygous for the minor allele of rs1453542 had a higher risk of neutropenia, and for rs5925720 the minor allele was associated with a lower risk for thrombocytopenia.
Conclusions: We have identified two new genetic markers with the potential to predict myelosuppression induced by gemcitabine/carboplatin chemotherapy. Clin Cancer Res; 22(2); 366–73. ©2015 AACR.
Translational Regulation of the Mitochondrial Genome Following Redistribution of Mitochondrial MicroRNA in the Diabetic Heart
Authors: Jagannathan Rajaganapathi , Thapa Dharendra , Nichols Cody E. , Shepherd Danielle L. , Stricker Janelle C. , Croston Tara L. , Baseler Walter A. , Lewis Sara E. , Martinez Ivan , Hollander John M. 
Published: September 2015

Background—
Cardiomyocytes are rich in mitochondria which are situated in spatially distinct subcellular regions, including those under the plasma membrane, subsarcolemmal mitochondria, and those between the myofibrils, interfibrillar mitochondria. We previously observed subpopulation-specific differences in mitochondrial proteomes following diabetic insult. The objective of this study was to determine whether mitochondrial genome–encoded proteins are regulated by microRNAs inside the mitochondrion and whether subcellular spatial location or diabetes mellitus influences the dynamics.

Methods and Results—
Using microarray technology coupled with cross-linking immunoprecipitation and next generation sequencing, we identified a pool of mitochondrial microRNAs, termed mitomiRs, that are redistributed in spatially distinct mitochondrial subpopulations in an inverse manner following diabetic insult. Redistributed mitomiRs displayed distinct interactions with the mitochondrial genome requiring specific stoichiometric associations with RNA-induced silencing complex constituents argonaute-2 (Ago2) and fragile X mental retardation–related protein 1 (FXR1) for translational regulation. In the presence of Ago2 and FXR1, redistribution of mitomiR-378 to the interfibrillar mitochondria following diabetic insult led to downregulation of mitochondrially encoded F0 component ATP6. Next generation sequencing analyses identified specific transcriptome and mitomiR sequences associated with ATP6 regulation. Overexpression of mitomiR-378 in HL-1 cells resulted in its accumulation in the mitochondrion and downregulation of functional ATP6 protein, whereas antagomir blockade restored functional ATP6 protein and cardiac pump function.

Conclusions—
We propose mitomiRs can translationally regulate mitochondrially encoded proteins in spatially distinct mitochondrial subpopulations during diabetes mellitus. The results reveal the requirement of RNA-induced silencing complex constituents in the mitochondrion for functional mitomiR translational regulation and provide a connecting link between diabetic insult and ATP synthase function.
Differences in Quality of Life Between Atrial Fibrillation Patients with Low Stroke Risk Treated With and Without Catheter Ablation
Authors: Bai Ying , Bai Rong , Wu Jia‐Hui , Zhang Ting , Liu Nian , Shi Xu‐Bo , Liu Xin‐Yao , Liu Xiao‐Hui , Du Xin , Dong Jian‐Zeng , Ma Chang‐Sheng 
Published: September 2015

Background

Impacts of a single radiofrequency ablation (
RFA
) on quality of life (QoL) were not well investigated in atrial fibrillation (
AF
) patients with low stroke risk.

Methods and Results

Nine hundred
AF
patients with low
CHADS
2
score (ie,
CHADS
2
≤1) who completed both a baseline and 6‐month Atrial Fibrillation Effect on QualiTy‐of‐life (
AFEQT
) questionnaire were selected from The Chinese Atrial Fibrillation Registry between 2011 and 2013. A final cohort of 222 patients was constructed after a propensity score matching with 74 in the
RFA
group and 148 in the non‐
RFA
group. Domains of
AFEQT
were balanced at baseline between the 2 groups. No statistically significant differences were noted in QoL (all
P
>0.05) when
AFEQT
at 6 months was compared between groups, except for the symptoms domain (83.07±12.37 units in the
RFA
group vs. 77.68±17.14 units in the non‐
RFA
group;
P
=0.008) and treatment satisfaction domain (76.34±14.92 units in the
RFA
group vs. 70.38±16.81 units in the non‐
RFA
group;
P
=0.01). Within‐group changes in all domains and the global score of the questionnaire were moderate to large, whereas between‐group comparisons in baseline to 6‐month changes and QoL at 6 months were small to moderate according to Cohen effect sizes.

Conclusions

QoL was balanced at baseline and improved at 6 months in both groups from this observational propensity‐matched cohort based on the
AFEQT
questionnaire. However,
RFA
treatment was only associated with small‐to‐moderate superiorities over non‐
RFA
treatment. The role of
RFA
in QoL improvement among
AF
patients with low stroke risk requires further research.
<strong>The genus Chorisodontium (Dicranaceae, Musci) in the Neotropics</strong>
Authors: Frahm Jan-Peter 
Published: September 2015

All the species of Chorisodontium recorded from the neotropical mountains (Bolivia Costa Rica) have been critically revised. Three species, C. nigricans Herz., C. mittenii (C. Müll.) Broth. and C. wallisii (C. Müll.) Broth. are accepted. Chorisodontium speciosum (Hook. f. & Wils.) Broth. is placed as a variety to C. wallisii.
Exploring Winter Mortality Variability in Five Regions of England Using Back Trajectory Analysis
Authors: Dimitriou K. , McGregor G. R. , Kassomenos P. A. , Paschalidou A. K. 
Published: September 2015

Abstract
This paper aims to define atmospheric pathways related with the occurrence of daily winter low temperature episodes (LTE) in England, for the 26-yr period 1974–99, and to reveal possible associations with increased mortality rates. For this purpose, backward airmass trajectories, corresponding to LTE in five regions of England, were deployed. A statistically significant increase in mortality levels, at the 0.05 level, was found for LTE, compared to non-LTE days across all five regions. Seven categories of atmospheric trajectory patterns associated with LTE were identified: east, local, west, North Atlantic, Arctic, southwest, and Scandinavian. Consideration of the link between airmass trajectory patterns and mortality levels by region revealed a possible west-to-east split in the nature of air masses connected with elevated mortality. Specifically, for the West Midlands and northwest regions, relatively warm winter weather conditions from the west, most likely associated with the eastward progression of low pressure systems, are allied with the highest daily average mortality counts, whereas, for the northeast, Humberside/York, and southeast regions, cold continental air advection from northern or eastern Europe, which lasts for several days and is linked with either a blocking pattern over the western margins of Europe or an intense high pressure anomaly over eastern or northern Europe, appears important in mortality terms. This finding confirms that winter weather health associations are complex, such that climate setting and airmass climatology need to be taken into account when considering climate and health relationships.