bluuebunny/crossref_metadata_2025_split huggingface dataset:
Use of Colorimetric Culture Methods for Detection of Mycobacterium tuberculosis Complex Isolates from Sputum Samples in Resource-Limited Settings
Authors: Boum Yap , Orikiriza Patrick , Rojas-Ponce Gabriel , Riera-Montes Margarita , Atwine Daniel , Nansumba Margaret , Bazira Joel , Tuyakira Eleanor , De Beaudrap Pierre , Bonnet Maryline , Page Anne-Laure 
Published: May 2013

ABSTRACT

Despite recent advances, tuberculosis (TB) diagnosis remains imperfect in resource-limited settings due to its complexity and costs, poor sensitivity of available tests, or long times to reporting. We present a report on the use of colorimetric methods, based on the detection of mycobacterial growth using colorimetric indicators, for the detection of
Mycobacterium tuberculosis
in sputum specimens. We evaluated the nitrate reductase assay (NRA), a modified NRA using
para
-nitrobenzoic acid (PNB) (NRAp), and the resazurin tube assay using PNB (RETAp) to differentiate tuberculous and nontuberculous mycobacteria. The performances were assessed at days 18 and 28 using mycobacterium growth indicator tube (MGIT) and Löwenstein-Jensen (LJ) medium culture methods as the reference standards. We enrolled 690 adults with suspected pulmonary tuberculosis from a regional referral hospital in Uganda between March 2010 and June 2011. At day 18, the sensitivities and specificities were 84.6% and 90.0% for the NRA, 84.1% and 92.6% for the NRAp, and 71.2% and 99.3% for the RETAp, respectively. At day 28, the sensitivity of the RETAp increased to 82.6%. Among smear-negative patients with suspected TB, sensitivities at day 28 were 64.7% for the NRA, 61.3% for the NRAp, and 50% for the RETAp. Contamination rates were found to be 5.4% for the NRA and 6.7% for the RETAp, compared with 22.1% for LJ medium culture and 20.4% for MGIT culture. The median times to positivity were 10, 7, and 25 days for colorimetric methods, MGIT culture, and LJ medium culture,respectively. Whereas the low specificity of the NRA/NRAp precludes it from being used for TB diagnosis, the RETAp might provide an alternative to LJ medium culture to decrease the time to culture results in resource-poor settings.
Virus Detection and Semiquantitation in Explanted Heart Tissues of Idiopathic Dilated Cardiomyopathy Adult Patients by Use of PCR Coupled with Mass Spectrometry Analysis
Authors: Nguyen Yohan , Renois Fanny , Leveque Nicolas , Giusti Delphine , Picard-Maureau Marcus , Bruneval Patrick , Fornes Paul , Andreoletti Laurent 
Published: May 2013

ABSTRACT

Viral detection in heart tissues has become a central issue for the diagnosis and exploration of the pathogenesis of idiopathic dilated cardiomyopathy (IDCM). In the present study, common cardiotropic viruses in 67 explanted heart samples of 31 IDCM adult patients were detected and semiquantified by using for the first time a new technology based on PCR assay coupled to electrospray ionization-time of flight mass spectrometry analysis (PCR-MS), with comparison to reference quantitative real-time PCR (RT-qPCR) assay. PCR-MS identified single or mixed enterovirus (EV) and parvovirus B19 (PVB19) infections in 27 (40.2%) of 67 samples, corresponding to 15 (48.3%) of the 31 patients, whereas RT-qPCR identified viral infections in 26 (38.8%) samples, corresponding to 16 (51.6%) of the patients. The PCR-MS results correlated well with EV and PVB19 detection by RT-qPCR (kappa = 0.85 [95% confidence interval {CI}, 0.72 to 1.00] and kappa = 0.82 [95% CI, 0.66 to 0.99], respectively). The levels of EV RNA (median, 550 [range, 178 to 3,200] copies/μg of total extracted nucleic acids) and of PVB19 DNA (median, 486 [range, 80 to 1,157] copies/μg of total extracted nucleic acids) were measured using PCR-MS and correlated with those obtained by RT-qPCR (
r
2
= 0.57,
P
= 0.002 and
r
2
= 0.64,
P
< 0.001 for EV and PVB19, respectively). No viruses other than EV and PVB19 strains were detected using the new PCR-MS technology, which is capable of simultaneously identifying 84 known human viruses in one assay. In conclusion, we identified single or mixed EV and PVB19 cardiac infections as potential causes of IDCM. The PCR-MS analysis appeared to be a valuable tool to rapidly detect and semiquantify common viruses in cardiac tissues and may be of major interest to better understand the role of viruses in unexplained cardiomyopathies.
Helicobacter cinaedi and Helicobacter fennelliae Transmission in a Hospital from 2008 to 2012
Authors: Rimbara Emiko , Mori Shigetarou , Kim Hyun , Matsui Mari , Suzuki Satowa , Takahashi Shunji , Yamamoto Satoshi , Mukai Masaya , Shibayama Keigo 
Published: May 2013

ABSTRACT

Forty-six
Helicobacter cinaedi
isolates from the same hospital were analyzed by multilocus sequence typing. Most
H. cinaedi
isolates exhibited clonal complex 9 and were mainly isolated from immunocompromised patients in the same ward. Three
Helicobacter fennelliae
isolates were obtained from the same ward and exhibited the same pulsed-field gel electrophoresis patterns. All isolates were resistant to clarithromycin and ciprofloxacin.
H. cinaedi
and
H. fennelliae
must be carefully monitored to prevent nosocomial infection.
Protection by Immunoglobulin Dual-Affinity Retargeting Antibodies against Dengue Virus
Authors: Brien James D. , Sukupolvi-Petty Soila , Williams Katherine L. , Lam Chia-Ying Kao , Schmid Michael A. , Johnson Syd , Harris Eva , Diamond Michael S. 
Published: May 2013

ABSTRACT

Dengue viruses are the most common arthropod-transmitted viral infection, with an estimated 390 million human infections annually and ∼3.6 billion people at risk. Currently, there are no approved vaccines or therapeutics available to control the global dengue virus disease burden. In this study, we demonstrate the binding, neutralizing activity, and therapeutic capacity of a novel bispecific
d
ual-
a
ffinity
r
e
t
argeting molecule (DART) that limits infection of all four serotypes of dengue virus.
The Resistance Protein Tm-1 Inhibits Formation of a Tomato Mosaic Virus Replication Protein-Host Membrane Protein Complex
Authors: Ishibashi Kazuhiro , Ishikawa Masayuki 
Published: May 2013

ABSTRACT

The
Tm-1
gene of tomato confers resistance to
Tomato mosaic virus
(ToMV).
Tm-1
encodes a protein that binds ToMV replication proteins and inhibits the RNA-dependent RNA replication of ToMV. The replication proteins of resistance-breaking mutants of ToMV do not bind Tm-1, indicating that the binding is important for inhibition. In this study, we analyzed how Tm-1 inhibits ToMV RNA replication in a cell-free system using evacuolated tobacco protoplast extracts. In this system, ToMV RNA replication is catalyzed by replication proteins bound to membranes, and the RNA polymerase activity is unaffected by treatment with 0.5 M NaCl-containing buffer and remains associated with membranes. We show that in the presence of Tm-1, negative-strand RNA synthesis is inhibited; the replication proteins associate with membranes with binding that is sensitive to 0.5 M NaCl; the viral genomic RNA used as a translation template is not protected from nuclease digestion; and host membrane proteins TOM1, TOM2A, and ARL8 are not copurified with the membrane-bound 130K replication protein. Deletion of the polymerase read-through domain or of the 3′ untranslated region (UTR) of the genome did not prevent the formation of complexes between the 130K protein and the host membrane proteins, the 0.5 M NaCl-resistant binding of the replication proteins to membranes, and the protection of the genomic RNA from nucleases. These results indicate that Tm-1 binds ToMV replication proteins to inhibit key events in replication complex formation on membranes that precede negative-strand RNA synthesis.
Polarized Cell Migration during Cell-to-Cell Transmission of Herpes Simplex Virus in Human Skin Keratinocytes
Authors: Abaitua Fernando , Zia F. Rabiya , Hollinshead Michael , O'Hare Peter 
Published: May 2013

ABSTRACTIn addition to transmission involving extracellular free particles, a generally accepted model of virus propagation is one wherein virus replicates in one cell, producing infectious particles that transmit to the next cell via cell junctions or induced polarized contacts. This mechanism of spread is especially important in the presence of neutralizing antibody, and the concept underpins analysis of virus spread, plaque size, viral and host functions, and general mechanisms of virus propagation. Here, we demonstrate a novel process involved in cell-to-cell transmission of herpes simplex virus (HSV) in human skin cells that has not previously been appreciated. Using time-lapse microscopy of fluorescent viruses, we show that HSV infection induces the polarized migration of skin cells into the site of infection. In the presence of neutralizing antibody, uninfected skin cells migrate to the initial site of infection and spread over infected cells to become infected in a spatially confined cluster containing hundreds of cells. The cells in this cluster do not undergo cytocidal cell lysis but harbor abundant enveloped particles within cells and cell-free virus within interstitial regions below the cluster surface. Cells at the base and outside the cluster were generally negative for virus immediate-early expression. We further show, using spatially separated monolayer assays, that at least one component of this induced migration is the paracrine stimulation of a cytotactic response from infected cells to uninfected cells. The existence of this process changes our concept of virus transmission and the potential functions, virus, and host factors involved.
Infectious Virion Capture by HIV-1 gp120-Specific IgG from RV144 Vaccinees
Authors: Liu Pinghuang , Yates Nicole L. , Shen Xiaoying , Bonsignori Mattia , Moody M. Anthony , Liao Hua-Xin , Fong Youyi , Alam S. Munir , Overman R. Glenn , Denny Thomas , Ferrari Guido , Ochsenbauer Christina , Kappes John C. , Polonis Victoria R. , Pitisuttithum Punnee , Kaewkungwal Jaranit , Nitayaphan Sorachai , Rerks-Ngarm Supachai , Montefiori David C. , Gilbert Peter , Michael Nelson L. , Kim Jerome H. , Haynes Barton F. , Tomaras Georgia D. 
Published: May 2013

ABSTRACT
The detailed examination of the antibody repertoire from RV144 provides a unique template for understanding potentially protective antibody functions. Some potential immune correlates of protection were untested in the correlates analyses due to inherent assay limitations, as well as the need to keep the correlates analysis focused on a limited number of endpoints to achieve statistical power. In an RV144 pilot study, we determined that RV144 vaccination elicited antibodies that could bind infectious virions (including the vaccine strains HIV-1 CM244 and HIV-1 MN and an HIV-1 strain expressing transmitted/founder Env, B.WITO.c). Among vaccinees with the highest IgG binding antibody profile, the majority (78%) captured the infectious vaccine strain virus (CM244), while a smaller proportion of vaccinees (26%) captured HIV-1 transmitted/founder Env virus. We demonstrated that vaccine-elicited HIV-1 gp120 antibodies of multiple specificities (V3, V2, conformational C1, and gp120 conformational) mediated capture of infectious virions. Although capture of infectious HIV-1 correlated with other humoral immune responses, the extent of variation between these humoral responses and virion capture indicates that virion capture antibodies occupy unique immunological space.
Assessment of the Protective Effect of Imvamune and Acam2000 Vaccines against Aerosolized Monkeypox Virus in Cynomolgus Macaques
Authors: Hatch Graham J. , Graham Victoria A. , Bewley Kevin R. , Tree Julia A. , Dennis Mike , Taylor Irene , Funnell Simon G. P. , Bate Simon R. , Steeds Kimberley , Tipton Thomas , Bean Thomas , Hudson Laura , Atkinson Deborah J. , McLuckie Gemma , Charlwood Melanie , Roberts Allen D. G. , Vipond Julia 
Published: May 2013

ABSTRACT

To support the licensure of a new and safer vaccine to protect people against smallpox, a monkeypox model of infection in cynomolgus macaques, which simulates smallpox in humans, was used to evaluate two vaccines, Acam2000 and Imvamune, for protection against disease. Animals vaccinated with a single immunization of Imvamune were not protected completely from severe and/or lethal infection, whereas those receiving either a prime and boost of Imvamune or a single immunization with Acam2000 were protected completely. Additional parameters, including clinical observations, radiographs, viral load in blood, throat swabs, and selected tissues, vaccinia virus-specific antibody responses, immunophenotyping, extracellular cytokine levels, and histopathology were assessed. There was no significant difference (
P
> 0.05) between the levels of neutralizing antibody in animals vaccinated with a single immunization of Acam2000 (132 U/ml) and the prime-boost Imvamune regime (69 U/ml) prior to challenge with monkeypox virus. After challenge, there was evidence of viral excretion from the throats of 2 of 6 animals in the prime-boost Imvamune group, whereas there was no confirmation of excreted live virus in the Acam2000 group. This evaluation of different human smallpox vaccines in cynomolgus macaques helps to provide information about optimal vaccine strategies in the absence of human challenge studies.
DNA Topoisomerase 1 Facilitates the Transcription and Replication of the Ebola Virus Genome
Authors: Takahashi Kei , Halfmann Peter , Oyama Masaaki , Kozuka-Hata Hiroko , Noda Takeshi , Kawaoka Yoshihiro 
Published: May 2013

ABSTRACT
Ebola virus (EBOV) protein L (EBOL) acts as a viral RNA-dependent RNA polymerase. To better understand the mechanisms underlying the transcription and replication of the EBOV genome, we sought to identify cellular factors involved in these processes via their coimmunoprecipitation with EBOL and by mass spectrometry. Of 65 candidate proteins identified, we focused on DNA topoisomerase 1 (TOP1), which localizes to the nucleus and unwinds helical DNA. We found that in the presence of EBOL, TOP1 colocalizes and interacts with EBOL in the cytoplasm, where transcription and replication of the EBOV genome occur. Knockdown of TOP1 markedly reduced virus replication and viral polymerase activity. We also found that the phosphodiester bridge-cleaving and recombination activities of TOP1 are required for the polymerase activity of EBOL. These results demonstrate that TOP1 is an important cellular factor for the transcription and replication of the EBOV genome and, as such, plays a key role in the EBOV life cycle.
Randomised controlled trial of an education and support package for stroke patients and their carers
Authors: Eames Sally , Hoffmann Tammy , Worrall Linda , Read Stephen , Wong Andrew 
Published: May 2013

ObjectiveTailoring stroke information and providing reinforcement opportunities are two strategies proposed to enhance the effectiveness of education. This study aimed to evaluate the effects of an education package which utilised both strategies on the knowledge, health and psychosocial outcomes of stroke patients and carers.DesignMultisite, randomised trial comparing usual care with an education and support package.SettingTwo acute stroke units.ParticipantsPatients and their carers (N=138) were randomised (control n=67, intervention n=71) of which data for 119 participants (control n=59, intervention n=60) were analysed.InterventionThe package consisted of a computer-generated, tailored written information booklet and verbal reinforcement provided prior to, and for 3 months following, discharge.Outcome measuresOutcome measures were administered prior to hospital discharge and at 3-month follow-up by blinded assessors. The primary outcome was stroke knowledge (score range: 0–25). Secondary outcomes were: self-efficacy (1–10), anxiety and depression (0–21), ratings of importance of information (1–10), feelings of being informed (1–10), satisfaction with information (1–10), caregiver burden (carers) (0–13) and quality of life (patients) (1–5).ResultsIntervention group participants reported better: self-efficacy for accessing stroke information (adjusted mean difference (MD) of 1.0, 95% CI 0.3 to 1.7, p=0.004); feeling informed (MD 0.9, 95% CI 0.2 to 1.6, p=0.008); and satisfaction with medical (MD 2.0, 95% CI 1.1 to 2.8, p<0.001); practical (MD 1.1, 95% CI 0.3 to 1.9, p=0.008), services and benefits (MD 0.9, 95% CI 0.1 to 1.8, p=0.036) and secondary prevention information (MD 1.7, 95% CI 0.9 to 2.5, p<0.001). There was no significant effect on other outcomes.ConclusionsIntervention group participants had improved self-efficacy for accessing stroke information and satisfaction with information, but other outcomes were not significantly affected. Evaluation of a more intensive intervention in a trial with a larger sample size is required to establish the value of an educational intervention that uses tailoring and reinforcement strategies.ACTRN12608000469314
An observational study of nurse staffing ratios and hospital readmission among children admitted for common conditions
Authors: Tubbs-Cooley Heather L , Cimiotti Jeannie P , Silber Jeffrey H , Sloane Douglas M , Aiken Linda H 
Published: May 2013

BackgroundHospital patient-to-nurse staffing ratios are associated with quality outcomes in adult patient populations but little is known about how these factors affect paediatric care. We examined the relationship between staffing ratios and all-cause readmission (within 14 days, 15–30 days) among children admitted for common medical and surgical conditions.MethodsWe conducted an observational cross-sectional study of readmissions of children in 225 hospitals by linking nurse surveys, inpatient discharge data and information from the American Hospital Association Annual Survey. Registered Nurses (N=14 194) providing direct patient care in study hospitals (N=225) and children hospitalised for common conditions (N=90 459) were included.ResultsEach one patient increase in a hospital's average paediatric staffing ratio increased a medical child's odds of readmission within 15–30 days by a factor of 1.11, or by 11% (95% CI 1.02 to 1.20) and a surgical child's likelihood of readmission within 15–30 days by a factor of 1.48, or by 48% (95% CI 1.27 to 1.73). Children treated in hospitals with paediatric staffing ratios of 1 : 4 or less were significantly less likely to be readmitted within 15–30 days. There were no significant effects of nurse staffing ratios on readmissions within 14 days.DiscussionChildren with common conditions treated in hospitals in which nurses care for fewer patients each are significantly less likely to experience readmission between 15 and 30 days after discharge. Lower patient-to-nurse ratios hold promise for preventing unnecessary hospital readmissions for children through more effective predischarge monitoring of patient conditions, improved discharge preparation and enhanced quality improvement success.
Association between 8-oxo-7,8-dihydro-2′-deoxyguanosine Excretion and Risk of Postmenopausal Breast Cancer: Nested Case–Control Study
Authors: Loft Steffen , Olsen Anja , Møller Peter , Poulsen Henrik E. , Tjønneland Anne 
Published: May 2013

Abstract
Background: Oxidative stress may be important in carcinogenesis and a possible risk factor for breast cancer. The urinary excretion of oxidatively generated biomolecules, such as 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodG), represents biomarkers of oxidative stress, reflecting the rate of global damage to DNA in steady state.
Methods: In a nested case–control design, we examined associations between urinary excretion of 8-oxodG and risk of breast cancer in a population-based cohort of 24,697 postmenopausal women aged 50 to 64 years with 3 to 7 years follow-up. The accruing cases of breast cancer were matched to controls by age at diagnosis, baseline age, and hormone replacement therapy (HRT). Spot urine samples collected at entry was analyzed for 8-oxodG by high-performance liquid chromatography with electrochemical detection. Incidence rate ratio (IRR; 95% confidence intervals) based on 336 matched pairs with all information was estimated per unit increase in 8-oxodG divided by creatinine for all and estrogen receptor (ER) positive and negative breast cancers.
Results: There was a borderline significant positive association between 8-oxodG and risk of all breast cancer (IRR: 1.08; 1.00–1.17 per unit increase in nmol/mmol creatinine). This association was significant with respect to the risk of ER-positive cancer (IRR: 1.11; 1.01–1.23) and among women not using HRT (IRR: 1.11; 0.97–1.26) or with low dietary iron intake (IRR: 1.10; 1.06–1.37 per unit increase) for all breast cancer.
Conclusions: We observed positive association between 8-oxodG excretion and risk of especially ER-positive breast cancer.
Impact: Our results suggest that oxidative stress with damage to DNA is important for the development of breast cancer. Cancer Epidemiol Biomarkers Prev; 22(7); 1289–96. ©2013 AACR.
High Prevalence of BRCA1 and BRCA2 Germline Mutations with Loss of Heterozygosity in a Series of Resected Pancreatic Adenocarcinoma and Other Neoplastic Lesions
Authors: Lucas Aimee L. , Shakya Reena , Lipsyc Marla D. , Mitchel Elana B. , Kumar Sheila , Hwang Caroline , Deng Liyong , Devoe Catherine , Chabot John A. , Szabolcs Matthias , Ludwig Thomas , Chung Wendy K. , Frucht Harold 
Published: May 2013

Abstract
Purpose: Pancreatic ductal adenocarcinoma (PDAC) is associated with the breast ovarian cancer syndrome (BRCA1/BRCA2) mutations. It is unknown if this association is causal.
Experimental Design: This is a single-site study of patients who underwent surgical pancreatic tumor resection and self-identified as Ashkenazi Jewish. DNA from normal pancreatic tissue was genotyped for the three Ashkenazi Jewish BRCA1/2 founder mutations BRCA1 185delAG, BRCA1 5382insC, and BRCA2 6174delT, and loss of heterozygosity (LOH) was determined by sequencing DNA from microdissected tumor. When additional tumor tissue was available, p53 immunohistochemistry (IHC) was conducted.
Results: Thirty-seven patients underwent surgery for PDAC, seven for intraductal papillary mucinous neoplasm (IPMN), and 19 for other diseases. A high prevalence of BRCA1/2 mutations was found in the surgical cohort (12/63; 19.0%; P &lt; 0.001), PDAC cohort (8/37; 21.6%; P &lt; 0.001), and IPMN cohort (2/7; 28.6%; P = .01) compared with published control mutation frequency. A high prevalence of BRCA1 185delAG (8.1%; P &lt; 0.001) and BRCA2 6174delT (10.8%; P &lt; 0.001) in Ashkenazi Jewish patients with PDAC was shown. BRCA1/2 LOH was found in 2 of 4 BRCA1-associated PDACs and 3 of 4 BRCA2-associated PDACs. Positive p53 IHC was found in 5 of 8 BRCA1/2 PDACs.
Conclusions: We show a high prevalence of BRCA1/2 mutations with LOH in an Ashkenazi Jewish cohort of surgically resected PDAC and neoplastic lesions, suggesting that these germline mutations are causal in selected individuals. Clin Cancer Res; 19(13); 3396–403. ©2013 AACR.